Comprehensive Organic Functional Group Transformations, Volume 6 Elsevier, 2003 Editors-in-Chief: Alan R. Katritzky, Oth...
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Comprehensive Organic Functional Group Transformations, Volume 6 Elsevier, 2003 Editors-in-Chief: Alan R. Katritzky, Otho Meth-Cohn, and Charles W. Rees
Synthesis: Carbon with Three or Four Attached Heteroatoms Part I: Tetracoordinated Carbon with Three Attached Heteroatoms, RCXX′X″ 6.01 Trihalides, Pages 1-33, Richard D. Chambers and John Hutchinson 6.02 Functions Containing Halogens and Any Other Elements, Pages 35-66, Graham B. Jones and Jude E. Matthews 6.03 Functions Containing Three Chalcogens (and No Halogens), Pages 67-102, Glynn Mitchell 6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen, Pages 103-136, Martin J. Rice 6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 137-170, David P. J. Pearson 6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen or Group 15 Element; Also Functions Containing Three Metals, Pages 171-210, Vadim D. Romanenko, Michel Sanchez and Jean-Marc Sotiropoulos Part II: Tetracoordinated Carbon with Four Attached Heteroatoms, CXX′X″X‴ 6.07 Functions Containing Four Halogens or Three Halogens and One Other Heteroatom Substituent, Pages 211-247, Alex H. Gouliaev and Alexander Senning 6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents, Pages 249-270, Anastassios Varvoglis
by kmno4
6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents, Pages 271-293, Angela Marinetti and Philippe Savignac 6.10 Functions Containing Four or Three Chalcogens (and No Halogens), Pages 295-318, Alex H. Gouliaev and Alexander Senning 6.11 Functions Containing Two or One Chalcogens (and No Halogens), Pages 319-358, Wolfgang Petz and Frank Weller 6.12 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen), Pages 359-375, Duncan Carmichael, Angela Marinetti and Philippe Savignac 6.13 Functions Containing at Least One Metalloid (Si, Ge or B) and No Halogen, Chalcogen or Group 15 Element; Also Functions Containing Four Metals, Pages 377-406, Paul D. Lickiss Part III: Tricoordinated Carbon with Three Attached Heteroatoms, Y=CXX′ 6.14 Functions Containing a Carbonyl Group and at Least One Halogen, Pages 407-457, Geoffrey E. Gymer and Subramaniyan Narayanaswami 6.15 Functions Containing a Carbonyl Group and at Least One Chalcogen (but No Halogen), Pages 459-498, Heiner Eckert and Alfons Nestl 6.16 Functions Containing a Carbonyl Group and Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 499-526, Anthony F. Hegarty and Leo J. Drennan 6.17 Functions Containing a Thiocarbonyl Group and at Least One Halogen; Also at Least One Chalcogen and No Halogen, Pages 527-567, Erich Kleinpeter and Kalevi Pihlaja 6.18 Functions Containing a Thiocarbonyl Group Bearing Two Heteroatoms Other Than a Halogen or Chalcogen, Pages 569-585, José Barluenga, Eduardo Rubio and Miguel Tomás 6.19 Functions Containing a Selenocarbonyl or Tellurocarbonyl Group—SeC(X)X′ and TeC(X)X′, Pages 587-599, Frank S. Guziec and Lynn J. Guziec 6.20 Functions Containing an Iminocarbonyl Group and at Least One Halogen; Also One Chalcogen and No Halogen, Pages 601-637, Thomas L. Gilchrist 6.21 Functions Containing an Iminocarbonyl Group and Any Elements Other Than a Halogen or Chalcogen, Pages 639-675, Ian A. Cliffe 6.22 Functions Containing Doubly Bonded P, As, Sb, Bi, Si, Ge, B or a Metal, Pages 677-724, Vadim D. Romanenko, Michel Sanchez and Lydia Lamandé Part IV: Tricoordinated Stabilized Cations and Radicals, +CXYZ and ·CXYZ 6.23 Tricoordinated Stabilized Cations and Radicals, +CXYZ and ·CXYZ, Pages 725-734, Thomas L. Gilchrist 6.24 References to Volume 6, Pages 735-844
by kmno4
6.01 Trihalides RICHARD D. CHAMBERS University of Durham, UK and JOHN HUTCHINSON BNFL Fluorochemicals Ltd., Durham, UK 5[90[0 GENERAL METHODS
0
5[90[0[0 The Addition of Halo`ens and Interhalo`en Compounds to Fluoroalkenes 5[90[0[1 The Addition of Haloalkanes to Haloalkenes 5[90[0[1[0 Lewis acid!catalysed addition of trihalomethyl cations to haloalkenes*the Prins reaction 5[90[0[1[1 Additions initiated by free radicals\ heat or radiation 5[90[0[1[2 Additions catalysed by salts and complexes of transition metals 5[90[0[1[3 Additions induced electrochemically 5[90[0[2 The Preparation of C1 Chloro~uorohydrocarbons
1 3 3 3 5 6 6
5[90[1 TRIFLUOROMETHYL DERIVATIVES*RCF2 5[90[1[0 General 5[90[1[1 Aryl Derivatives 5[90[1[1[0 Conversion of `roups attached to an aromatic rin` into the tri~uoromethyl `roup 5[90[1[1[1 Substitution by tri~uoromethyl radicals 5[90[1[1[2 Substitution of hydro`en by the tri~uoromethyl `roup actin` as an electrophile 5[90[1[1[3 Substitution of halo`ens by the tri~uoromethyl `roup actin` as a nucleophile 5[90[1[1[4 Substitution of halo`ens by the tri~uoromethyl `roup usin` derivatives of metals 5[90[1[2 Derivatives of Alkanes\ Alkenes\ Alkynes and Other Saturated Compounds 5[90[1[2[0 Halo`en exchan`e 5[90[1[2[1 Conversions of other `roups to the tri~uoromethyl `roup 5[90[1[2[2 Transfer of tri~uoromethyl `roups as radicals 5[90[1[2[3 Reactions involvin` tri~uoromethyl derivatives of metals and metalloids
8 8 8 8 00 01 02 03 05 05 08 19 11
5[90[2 TRICHLOROMETHYL DERIVATIVES*RCCl2 5[90[2[0 Trichloromethyl Groups Attached to an Aliphatic Centre 5[90[2[0[0 Conversion of `roups attached to an aliphatic centre into the trichloromethyl `roup 5[90[2[0[1 Transfer of the trichloromethyl `roup to an aliphatic centre 5[90[2[1 Trichloromethyl Groups Attached to an Aromatic Rin` 5[90[2[1[0 Conversion of `roups attached to an aromatic rin` into the trichloromethyl `roup 5[90[2[1[1 Transfer of the trichloromethyl `roup to an aromatic rin`
12 12 12 12 16 17 18
5[90[3 TRIBROMOMETHYL DERIVATIVES*RBr2
20
5[90[4 MIXED SYSTEMS WITH FLUORINE*RCF1Hal
21
5[90[5 MIXED HALOFORMS*CHXY1 AND CHXYZ
21
5[90[0 GENERAL METHODS There are several general methods which can lead to trihalomethyl compounds where the halogen atoms can be the same or di}erent[ It will be seen that some of these methods lead to compounds 0
1
Trihalides
in which there are two such trihalomethyl groups[ For simplicity\ the general methods are discussed _rst[
5[90[0[0 The Addition of Halogens and Interhalogen Compounds to Fluoroalkenes The addition of halogens and interhalogen compounds to ~uoroalkenes a}ords a valuable method for the preparation of compounds containing the group 0CHal2 where the halogen atoms may be the same or di}erent[ The addition of halogens is conveniently carried out under ultraviolet irradiation "Equations "0# and "1## ð30JA2365\ 57JOC0905Ł\ but the addition of iodine to tetra~uoroethene occurs only at elevated temperatures "Equation "2## ð38JCS1837\ 38JOC636\ 42JCS0437\ 52USP2965930Ł[ Generally the yields of the adducts are high\ but when 0\0!di~uoroethene is treated with iodine a mixture of compounds is obtained\ the most abundant of which is CF2CH1I "Equation "3## ð47JOC211Ł[ F3C
Cl
F
Cl
F3C F Cl
Cl2, UV
Cl Cl Cl
OH
OH F
RF F F F
(1)
F
RF
Br2, UV
F Br
F F
i, ii or iii
F
F
I
I
F
F
(2)
F Br
(3)
F
i, I2, Et2O, 60 °C, 15 h; ii, I2, 150 °C, 24 h; iii, I2, KI, H2O, 100 °C, 5 h F
I2, 185 °C, 16 h
F
F
I
+ F
F
F
F
F
I
+
F
(4) F
F
F
I
+
The addition of the interhalogen compounds ICl and IBr to ~uoroalkenes also can be used to give compounds having the group 0CHal2[ With asymmetric alkenes\ the addition is regioselective\ but the precise composition of the product is in~uenced by the reaction conditions and the presence of catalysts[ The reactions shown in Equations "4#Ð"8# were carried out by several workers and thus under di}erent sets of conditions ð41JCS3312\ 43JCS812\ 50JCS2668\ 50JA1384\ 51JOC0371\ 53JOC141Ł^ the yields and\ where more than one isomer was obtained\ isomer ratios were correspondingly di}erent[ F
F
+ ICl F
Cl
F
F
+ ICl
F
Cl Cl
F
F
F
Cl
F
F
F F
F
F
Br Cl
I
+ IBr
I
Cl
+ IBr F
F
F
Cl
I
F
F
F
I
F
Cl
F
Cl
F
F
F
Cl
Cl
+
(5)
(6)
Cl
+
F
F
F Cl
Cl Cl Cl Cl
F
Cl
+
+ F
+ ICl
F
F
I
F F
F I
Br
I
(7)
I
(8)
I (9)
Br F
The elements bromine and ~uorine\ or iodine and ~uorine\ can be added to ~uoroalkenes by treating the alkene with a mixture of bromine tri~uoride and bromine\ or iodine penta~uoride and iodine "Equations "09#Ð"11##[ Here\ {IF| refers to a stoichiometric mixture of iodine penta~uoride
2
General Methods
and iodine "IF4 ¦1I1 04{IF|#\ and {BrF| to a stoichiometric mixture of bromine tri~uoride and bromine "BrF2 ¦Br1 02{BrF|#[ While the addition of {BrF| to ~uoroalkenes is vigorous and needs to be moderated\ the corresponding reactions of {IF| are carried out at elevated temperatures ð50JCS2668Ł\ and catalysts may be added ð50JA1272\ 73JAP4840114Ł[ The addition of {IF| to tetra! ~uoroethene is particularly important because the product\ penta~uoroiodoethane\ is a starting material in one of the commercial routes to ~uorochemical surfactants and surface treatments ðB! 68MI 590!90Ł[ Additions to hexa~uoropropene and 0\0!di~uoroethene give single isomers\ but additions to chlorotri~uoroethene and 0\0!dichlorodi~uoroethene yield mixtures of isomers whose composition is related to the reaction conditions[ The reaction of {IF| to tetrachloroethene results in ~uorination only "Equation "07##[ For the addition of {IF| to internal alkenes with the formula CF2"CF1#nCF1C"CF2#1\ special procedures are necessary "Equation "11##[ Either potassium ~uoride must be added to the {IF| mixture\ or the alkene may _rst be treated with AgF or AgF:KF in a polar aprotic solvent to make the silver salt\ which in turn is treated with iodine to give the desired product ð76JFC"26#112Ł[ These products are tertiary per~uoroiodoalkanes and are highly toxic\ so special care must be taken during their preparation[ F
F
+ 'IF' F
F
F 3C
+ 'IF'
F
F F
F
+ 'IF' F
Cl
F
Cl
F
F
Cl
F
Cl
Cl
F
Cl
F
F
F Cl
F
Cl
F
I
F
F
F
I
F
I
(14)
(15)
(16)
(17)
+ 'IF'
Cl Cl F
+ 'BrF'
F
Cl Cl
F
F F F
+ 'BrF' F
(13)
F
Cl
F3C
Cl F Cl
(12)
F
F
F
F
F Cl
F
F
Cl
F
F
F
+ 'IF'
F
I
Cl
+ 'IF'
(11)
F I
F
F I Cl
+ 'IF'
F F
+
F F
(10)
F
+
+ 'IF'
F
Cl
I
I F
F
F
I
F
Cl
F
F
F
+ 'IF'
F
F3C I F
F
F
F F
F
Cl Cl F
F
F
F
F Br
F3C F Br
(18)
(19)
F F F
(20)
3
Trihalides F
F
+ 'BrF' F
F
F
F
F Cl
Br
Cl
+ 'IF' CF3
F
F
F
F
Br Cl
F
CF3(CF2)n F F
CF3
CF3(CF2)n
+
CF3 CF3 I
(21)
(22)
5[90[0[1 The Addition of Haloalkanes to Haloalkenes The addition of haloalkanes to haloalkenes can be used to generate alkanes which bear a tri! halomethyl group "Equation "12##[ If the alkene is perhalogenated\ then it can be seen that the adduct will have two trihalomethyl groups[ These addition reactions can be initiated in four main ways\ that is\ by Lewis acids\ by free radical initiators\ by salts and complexes of certain transition metals\ and electrochemically[ RX
+
R
X
(23)
5[90[0[1[0 Lewis acid!catalysed addition of trihalomethyl cations to haloalkenes*the Prins reaction The aluminum chloride!catalysed addition of chloroalkanes to chloroalkenes has been known since the beginning of this century\ and is known as the Prins reaction ð03JPR304\ 24RTC138\ 24RTC296Ł[ More recently\ the reaction has been extended to include the addition of chloro~uoromethanes to ~uoroalkenes and chloro~uoroalkenes[ While most of the activity in this area occurred up to the early 0869s\ and was reviewed by Paleta ð66FCR28Ł and by Paleta and Posta ð61CLY826Ł\ interest has been renewed recently because the adducts may be intermediates in the manufacture of potential replacements for the higher!boiling chloro~uorocarbons "e[g[\ ð80MIP590!90\ 80EUP310211\ 81EUP362094\ 81JAP93053928Ł#[ Most commonly\ the halomethanes used in these reactions are CCl3\ CHCl2\ CFCl2 and CFHCl1\ and these have been added to the alkenes CF11CF1\ CF11CFCl\ CF11CCl1\ CFCl1CCl1\ CCl11CFCl\ C1Cl3\ CHCl1CHCl\ CF11CFH\ CF11CH1 and CF11CHCl "see Table 0#[ The addition of halomethanes to asymmetric perhalogenated ~uoroalkenes proceeds nonregiospeci_cally\ but corresponding additions to the hydrogen!containing alkenes CFCl1CFH\ CF11CFH\ CF11CH1 and CF11CHCl are highly regioselective\ with the electrophilic haloalkyl group becoming attached to the carbon which bears the hydrogen[ This suggests that the preferred isomer is that in which most of the ~uorine atoms on the precursor alkene are attached to the carbon where positive charge develops in the initial stages of the reaction[ In reactions with ~uorotrichloromethane\ both C0F and C0Cl bonds are cleaved\ although cleavage of the C0F bond is preferred due to the greater Al0F bond strength[ In its reaction with the alkenes CFCl1CHF and CF11CHCl the C0F bond is cleaved exclusively[ Some examples of these reactions are given in Table 0\ where it can be seen how the approach can be used to give a variety of propanes with various trihalomethyl groups attached to carbon atoms[ It is probable that the primary products in each of these reactions undergo rearrangement or further reaction\ and therefore the composition and nature of the observed products are dependent upon reaction conditions[
5[90[0[1[1 Additions initiated by free radicals\ heat or radiation When subjected to heat\ light\ or free radical initiators such as peroxides or azo compounds\ haloalkanes add to alkenes and haloalkenes "Scheme 0#[ Whether a simple adduct or a mixture of high molecular!weight telomers is obtained is determined by the relative rates of the propagation\ transfer and termination reactions[ Thus\ compounds with the weakest C0X bond\ that is\ iodides\ give lower molecular!weight products\ as do alkenes which are di.cult to polymerize under the conditions of the reaction[ But if the alkene is easily polymerized\ for example tetra~uoroethene\ or if the telogen is not particularly reactive\ high molecular!weight
4
General Methods Table 0 Lewis acid!catalysed addition of haloalkanes to haloalkenes[
ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Yield Composition Reactants Conditions ")# Products ")# Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * CF1CF1 ½14>C:2 h 69 CF2CF1CCl2\ CF1ClCF1CFCl1 72\ 06 60CCC0756 CFCl2 CHFCl1 CF1CF1 04>C:2[4 h 47 CF2CF1CHCl1\ CF1ClCF1CHFCl 48\ 30 60CCC0756 CF1CCl1 11>C:06 h 31 CF2CCl1CCl2\ CFCl1CF1CCl2\ 34\ 37\ 6 55CCC2473 CFCl2 CF1ClCCl1CFCl1 CHFCl1 CF1CCl1 6>C:01 h 67 CFCl1CF1CHCl1\ 70\ 08 56CCC2777 CF2CCl1CHCl1\ CCl2CF1CHFCl\ CF1ClCCl1CHFCl\ CF1ClCFClCHCl1 CFCl2 CF1CHF 9Ð03>C:6 h 54 CF2CHFCCl2\ CF1ClCHFCFCl1 69\ 29 63CCC0229 CHFCl1 CF1CHF 9>C:6 h 72 CF2CHFCHCl1\ 47\ 31 63CCC0229 CF1ClCHFCHFCl ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
Initiation R • + X•
RX
2 In•
or In2 In• + RX
R• + InX •
Propagation R• +
n
R n
Transfer •
+ RX
R
R
n
X
+ R•
n
Termination •
•
+
R
R
R
n
n
X• + X• •
X2
+ X•
R
R 2n
R
n
X n
Scheme 1
material is obtained[ With easily polymerized alkenes\ the telomerization can be controlled by using a large excess of the telogen "preferably an iodide or diiodide# and recycling the lower telomers[ This addition of a haloalkane is often regioselective\ and it is observed that the incoming radical generally attacks the least sterically hindered carbon[ However\ there is still debate on the factors which control the products of these reactions and the relative stability of the potential intermediate radicals\ and polar e}ects "note that trihalomethyl radicals are electrophilic# as well as steric e}ects all play their part[ This approach is used in the manufacture of C7 or C8 per~uoroalkyl iodides\ which are inter! mediates in the preparation of per~uorocarbon surfactants and surface treatments ðB!68MI 590!90Ł[ Illustrative examples of these addition reactions are given in Equations "13#Ð"24# "NB[ Higher telomers are also produced in these reactions# ð36JA0099\ 89JFC"36#150\ 49JA1102\ 42JOC217\ 42JCS811\ 42JCS2650\ 41JCS2389\ 53JOC0087\ 47JA740\ 76IZV797\ 44JA657\ 74T3492Ł "references refer to the respective Equations "13#Ð"24##\ but many more are recorded elsewhere ð52OR"02#80\ B!63MI 590!90\ B!65MI 590! 90Ł[ It is noteworthy that\ unlike other polyhaloalkanes\ trichloromethane adds to alkenes by hydrogen transfer "Equation "15##[
5
Trihalides R
+
CCl4
Cl
Cl
R (24)
Cl F
F
n-C6H13
+
Cl
F
F
F
Cl
Cl
Ph
+
(26) n-C6H13
Cl
Cl
Br (27)
Cl
+
CCl3I
F
F
F
Cl
F
Cl
F
F
Cl
I F
F
F
F
CN
F
F
F
I (30)
F
CF2Br2
OEt
+
F
CN Br
Br (31)
F
F CF2Br2
+
F
OEt
F
Br
F
Br F
F F
F
F CBr4
F
F
(29)
F F
+
F
Br F
F
F
Br
Br
F
F
Br
F F
+ F
CCl3Br
+
EtO2C
Cl
Br
F
(32)
F
(33)
F
F
CF2BrCl
(28)
F
I
F
F
+
CF3I
Ph
F
+
CF3I
(25)
RF
Cl
CCl3Br
Cl
Cl
RF
F
CCl3H
Cl
+
CCl4
Cl
F
(34)
F
EtO2C
CO2Et
Br
Cl Cl
CO2Et Cl
(35)
5[90[0[1[2 Additions catalysed by salts and complexes of transition metals In 0845 ð45CI"M#260Ł\ unexpected results were obtained when the thermal additions of CCl3 and CCl2H to acrylonitrile were carried out using a steel autoclave[ More of the 0 ] 0 adduct was obtained than expected\ and trichloromethane gave the adduct CHCl1CH1CHClCN rather than
6
General Methods
CCl2CH1CH1CN\ which is normally obtained in free radical additions to alkenes "vide supra#[ Later ð52JCS0776Ł\ it was established that copper"II# and iron"III# both catalysed the addition of tetrachloromethane to a variety of vinylic monomers\ and that 0 ] 0 adducts were frequently the sole products\ even with easily polymerized alkenes[ This discovery led to extensive work in the area\ and copper"II# has now been used to catalyse the addition of CCl3\ CCl2Br\ CCl1Br1\ CF2CCl2 and other chloro compounds to a large variety of alkenes and dienes[ It is worth noting that the addition of CF2CCl2 followed by hydrogenation of the adduct can be used to introduce a CF2CH1 group[ While most investigations in this area have used copper! and iron!based catalysts\ other metal salts such as samarium diiodide ð89JCS"P0#1920Ł and vanadium dichloride ð89SL106Ł have been used more recently[ As well as alkenes which contain only hydrogen\ halogenated alkenes and those which contain other groups have also been used[ Generally the 0 ] 0 adduct is the only product\ but higher telomers are produced when the alkene is halogenated[ However\ this method of initation always gives lower molecular!weight material than the corresponding peroxide initiated reaction[ Amines are often added to form complexes and {increase the solubility| of the copper\ and consequently to increase the reaction rate[ The following is not a comprehensive list of references but will serve to lead the reader into the area] ðB!63MI 590!90\ 64ACR054\ 65T1184\ 66TL3204\ 79CCC2377\ 79CCC2491\ 74PAC0716\ 76JPS"A#2914\ 78JFC"34#104\ 89JFC"36#84\ 80MI 590!90\ 81CCC0180\ 81JMOC40\ 82JFC"50#022Ł[ As well as metal oxides\ salts and their complexes with amines\ other transition metal complexes such as carbonyls of iron ð56JCS"C#0049\ 79JOC2846Ł and cobalt ð69JOC1871Ł\ carbonyl complexes of molybdenum ð71JCS"D#1170\ 89JOM"286#40Ł\ iron ð89JOM"275#118Ł and chromium ð73JOM"159#C64Ł\ and phosphine complexes of ruthenium ð62TL4036\ 64TL788\ 67JOC0623\ 74JOM"179#286\ 76JCS"P0#0404\ 81JOM40Ł\ rhodium ð70AG"E#364Ł\ rhenium ð76JCS"P0#0404Ł and palladium ð70CL0058\ 74T282Ł have all been found to be e.cient catalysts in this reaction[ When the chiral Ru2Cl3"diop#2 "diop\ 1\2!O! isopropylidene!1\2!dihydroxy!0\3!bis"diphenylphosphino#butane# was the catalyst\ chiral adducts were obtained ð76BCJ2576Ł[ Clearly the metal!catalysed additions of haloalkanes to haloalkenes proceed by a di}erent mechanism to those promoted by free radical initiators such as peroxides[ Any mechanism needs to be able to explain the {abnormal| addition of trichloromethane\ the suppression of the propagation step "0 ] 0 adducts are the main products#\ and the fact that the addition of tetrachloromethane to cyclohexene is highly stereoselective "with a ruthenium catalyst# compared with the situation which obtains when conventional radical initiators are used[ It is unlikely that the details of the mechanism will be the same for all the catalysts that have been identi_ed\ but it is generally believed that it is not a simple redox process but one in which "e[g[\ for CCl3# a trichloromethyl radical is formed on and bound to the catalyst prior to the addition to the alkene which is itself coordinated to the complex[
5[90[0[1[3 Additions induced electrochemically The free radical chain addition of various polyhalomethanes to alkenes has been initiated by electrochemically in situ generated manganese salts used in a catalytic amount associated with an equimolecular amount of a manganese"III# oxidizable compound such as methyl cyano! or acetoacetate[ In particular\ tetrabromomethane\ bromotrichloromethane\ dibromodi~uoromethane and n!heptadeca~uorooctyl iodide have been added to a variety of alkenes in high yield by this means "Equation "25## ð81TL102Ł[ X X R
+ CX3Y
Mn(II)
Y
X
(36)
anodic oxidation
R CX3 = CBr3, Y = Br; CX3 = CCl3, Y = Br; CX3 = CBrF2, Y = Br; CX3 = C7F15, Y = I
5[90[0[2 The Preparation of C1 Chloro~uorohydrocarbons The manufacture of saturated compounds having the general formula C1HxClyFz represents an important part of the ~uorochemical industry[ These compounds "x O# "chloro~uorocarbons* {CFC|s# have been used as refrigerants\ solvents and foam!blowing agents[ However\ because they
7
Trihalides
have been implicated in the destruction of ozone in the earth|s upper atmosphere\ they are being replaced\ under the terms of the Montreal Protocol\ by hydro~uorocarbons "y O# "{HFC|s# and\ for an interim period\ by hydrochloro~uorocarbons "{HCFC|s#[ The manufacture of these compounds is largely brought about by treating a chlorocarbon with hydrogen ~uoride and sometimes chlorine[ Other reactions in the process may include isomerization and hydrogenation[ The ~uorinations are carried out in either the liquid phase using an antimony"V# catalyst "Swarts| catalyst# or in the gas phase using a chromia!based catalyst[ The main routes to the C1 chloro~uorocarbons and those compounds which are replacing them are outlined in Scheme 1[ 0\0\0\1!Tetra~uoroethane "R023a# is to be the main {high!temperature| refrigerant "e[g[\ mobile air conditioning\ and domestic and industrial refrigeration# while 0\0\0!tri~uoroethane "R032a# and 0\0\0\1\1!penta~uoroethane "R014# will be used in compositions for {low!temperature| refrigeration and static air conditioning "e[g[\ ð82MI 590!90Ł#[ As well as having the uses outlined above\ some of these compounds are intermediates in the manufacture of products such as the anaesthetic halothane "CF2CHClBr#\ and monomers such as 0\0!di~uoroethene and chlorotri~uoroethene[
Cl
Cl
F
Cl
Cl
F
F F
F
F R134a
F R133a
F
Cl
F F Br Halothane Cl
Cl
Cl F Cl
F Cl
Cl
F
Cl
F
Cl
F
F
F
F
Cl R115
R114
Cl Cl F Cl R113a F
F
F F
F F
Cl
R113
F
F
F Cl
Cl R123
F F F
F
F F R125
Cl F Cl
R114a
F
F
F F
F
F
F R134a Cl Cl
F
F
R143a F Cl Cl
+
R141b Scheme 2
F F Cl R142b
F
+
F F R143a
8
Tri~uoromethyl 5[90[1 TRIFLUOROMETHYL DERIVATIVES*RCF2 5[90[1[0 General
There is a very considerable literature relating to the synthesis of organic compounds containing the tri~uoromethyl group\ and this stems principally from the importance of such compounds in the plant protection industry ð80MI 590!91Ł and\ to a lesser extent\ the pharmaceutical industry ðB! 80MI 590!92\ B!71MI 590!90Ł[ Amongst other e}ects\ the introduction of the tri~uoromethyl group increases the lipophilicity of bioactive molecules\ enhancing transport across cell walls\ and can reduce metabolism of a drug[ A major review ð81T5444Ł is focused on the synthesis of tri~uoromethyl derivatives\ and others ð80T2196\ 81T078\ 83TA826Ł include discussions of relevant methodology[ In considering this area\ it is appropriate to draw attention to the fact that processes which involve halogen exchange for ~uorine\ using anhydrous hydrogen ~uoride "AHF# as the source of ~uorine\ will be the most economically favourable for large!scale manufacture by industry\ which is remark! ably adept at handling AHF[ Such procedures are not\ however\ particularly easy on the laboratory scale\ and other approaches described here will frequently be preferred[ Furthermore\ the sensitivity of the molecule under consideration may well dictate the route that is most appropriate[ The considerations described above relate to compounds containing the tri~uoromethyl group as the only halocarbon unit\ but\ of course\ there is a very wide range of applications for more highly ~uorinated systems\ including their use as refrigerants and for other volatile inert ~uid applications\ membranes\ polymers and anaesthetics[
5[90[1[1 Aryl Derivatives 5[90[1[1[0 Conversion of groups attached to an aromatic ring into the tri~uoromethyl group Only the most reactive of organic halides will react with anhydrous hydrogen ~uoride without catalysis "see Section 5[90[0[2#\ but benzotrichloride is converted to the tri~uoride "Equation "26## ð41MI 590!90Ł\ and analogous systems\ including heterocyclic compounds\ may be obtained in this way "Equation "27## ð70AHC"17#0Ł[ More sophisticated techniques have been used in processes to chloro~uorinate side chains in a continuous process "Equation "28## ð79GEP2997970Ł[ Alternatively\ antimony tri~uoride may be used in classical ~uorination processes "Equation "39# ðB!65MI 590!91Ł\ where the product is obtained by simply distilling from the ~uorinating agent\ but the trichloroethyl moiety is much less e.cient for conversion to the tri~uoroethyl group "Equation "30## ð77JOC2526Ł[ A clever {one!pot| methodology is available for acid!induced trichloromethylation accompanied by exchange of chlorine for ~uorine "Equation "31## ð70JFC"07#170Ł[ CCl3
CF3 AHF
(37) 40 °C, autoclave 70%
CF3
CCl3 HF
(38) N
CCl3
204 °C 45%
Cl2, HF
N
300–600 °C 33%
N
CF3
N
Cl
F3C (39)
CF3
CCl3 SbF3 125 °C 58–66%
(40)
09
Trihalides F
Cl
Cl
CF3
CCl3
Cl
Cl
SbF3
+
Cl
+
(41)
SbCl5
NO2
NO2
NO2 48%
NO2
10%
33%
HF, CCl4
(42)
CF3 α:β=2:3
One of the most versatile methods available for introducing the tri~uoromethyl group involves reactions of benzoic acid derivatives and corresponding heterocyclic compounds with sulfur tetra~uoride "Equations "32#\ "33# and "34## ð74OR"23#208\ 70AHC"17#0\ 76JOM"214#02\ 82JFC"59#122Ł\ or the more convenient but less reactive diethylaminosulfur tri~uoride "DAST# ð64USP2803154\ 65USP2865580Ł and related systems "Equation "35## ð77OR"24#402Ł[ CF3
CO2H SF4, 150 °C
(43)
6h
HO2C
F3C
CO2H
CF3
33% conversion
HO2C
CO2H
HO2C
CO2H
SF4, 150–200°C 16 h
F F3C
CF3
F3C
CF3
F3C
+
O F3C F
66–76%
F
F
F
+
F
F
CO2H
F O
O F
8–12%
F 0.8–1.7%
(44)
F
CF3 SF4, HF 80–140 °C autoclave 55–92%
X
F
(45) X
X = OMe, Me, H, Cl, NO2 CO2H
CF3 Et2NSF3
(46)
NaF 50%
Thio derivatives "e[g[\ ortho!thioesters# may also be used for conversion to the tri~uoro! methyl moiety\ using NBS\ or its equivalent\ followed by pyridineÐhydrogen ~uoride "Equation "36## ð75TL3750Ł[ Dithiocarboxylate esters are converted in a similar process "Equation "37## ð81CL716Ł\ and dithiocarboxylate derivatives are also converted in an interesting process that involves xenon di~uoride "Equation "38## ð89TL2246Ł[ A very unusual conversion of a nitrile to the tri~uoromethyl derivative occurs\ using carbonyl ~uoride\ accompanied by other products "Equation "49## ð67IJ018Ł[
00
Tri~uoromethyl C(SMe)3
CF3 i, DBH
(47) ii, HF–pyridine 34%
NO2
NO2
DBH = 1,3-dibromo-5,5-dimethylhydantoin CS2Me
CF3 DBH, Bu4N+H2F3–
(48)
CF3
i, Mg, Et2O ii, CS2
(49)
Ar-X iii, XeF2 40–77%
X Ar = Ph, p-MeC6H4, m-CF3C6H4, α-naphthyl X = halogen (e.g., Br)
HF, NaF
+
(50)
COF2 4 d, 50 °C 20%
CN
CF3
5[90[1[1[1 Substitution by tri~uoromethyl radicals Primary sources of tri~uoromethyl radicals include tri~uoroethanoic acid and tri~uoro! methanesulfonic acid\ but iodo! or bromotri~uoromethanes are important sources that have been used extensively[ Various methods have been applied to generate tri~uoromethyl radicals from these sources ð81T5474\ 80TL6414Ł\ and these radicals are\ of course\ electrophilic in character[ Conse! quently\ a wide range of radical aromatic substitutions occur\ and these probably proceed more e}ectively with the more electron!rich aromatic compounds\ but\ in general\ they are not high! yielding processes "Equations "40#Ð"47## ð70JFC"06#234\ 76CC0690Ł[ hν
+
CF3I
O
N
NH
+
hν
CF3I
F3C
NH
N
(51)
CF3
O
DMF 24%
+ N
CF3 32%
Br
NH
(52)
47%
Br
+
(53)
CF3I CF3 61%, o : m : p = 40 : 30 : 22
NH2
NH2
+
CF3Br
Zn, SO2
(54) CF3
56%, o : p = 1.8 : 1
01
Trihalides OH
OH ButOOH
+
(55)
CF3SO2Na Cu(II)
CF3
45%, o : m : p = 4 : 1 : 6 70 °C
+
C6H6
(56)
C6H5CF3
(CF3CO)2O 54%
[CF3(CO)O]2
X
X = O (53%), NH (65%)
O
O CF3CO2H
HN
CF3
HN
electrolysis 60%
N H
O
(57)
CF3
X
(58) N H
O
Bis"tri~uoroacetyl# peroxide decomposes thermally and can be used to tri~uoromethylate elec! tron!rich aromatic compounds "Equations "48# and "59## ð89JFC"35#312Ł[ An atmosphere of ammonia has been used to promote the reaction of iodotri~uoromethane with pyridine "Equation "50## ð68JAP68172Ł[ Remarkably\ some cross!coupling between hexa~uorobenzene and bromotri~uoro! methane occurs over copper chromite "Equation "51## ð82JFC"50#0Ł\ and\ in other high!temperature chemistry\ polytetra~uoroethylene is used as a source of di~uorocarbene\ which\ under the con! ditions used\ is able to insert into carbonÐ~uorine bonds "Equation "52## ð58IZV085\ 63JCS"P0#097Ł[ 60 °C
+
[CF3(CO)O]2
S
70 °C
[CF3(CO)O]2
+
(59)
CF3
S
72%
(60)
CF3
71%
+
NH3
CF3I
(61)
CF3
180 °C, 24 h 60%
N
N α : β : γ = 46 : 40 : 13
copper chromite
+
C6F6
(62)
C6F5CF3
CF3Br 600 °C, flow 40%
F N
+
(–CF2–)n
CF3
550 °C
N 6%
CF3
F3C
+
F
F
(63)
N 60%
5[90[1[1[2 Substitution of hydrogen by the tri~uoromethyl group acting as an electrophile Nucleophilic attack at a saturated carbon contained in a highly halogenated system is\ in general\ very di.cult\ but Umemoto and co!workers have demonstrated that with superior leaving groups it is possible to e}ect what is\ formally\ nucleophilic attack on the tri~uoromethyl group "Equation "53##[ Very powerful per~uoroalkylating agents are available through so!called {FITS| reagents ""per~uoroalkyl#phenyliodonium iodides# ð73TL70\ 75JFC"20#26Ł[ So far\ the corresponding reagents
02
Tri~uoromethyl
are not available for the introduction of the tri~uoromethyl group\ although this may be a practical di.culty\ rather than a fundamental di}erence in reactivity between tri~uoromethyl and other per~uoroalkyl systems[ However\ a less powerful but e}ective series of salts of tellurium\ selenium and sulfur heterocycles has been developed which will transfer the tri~uoromethyl moiety ð82JA1045Ł\ and it is concluded that the process involves nucleophilic attack on the tri~uoromethyl group[ The overall process is illustrated in Scheme 2\ where the reactivity of the salts "0# varies in the series X Te³Se³S\ while electron!withdrawing substituents in the aromatic ring also increase reac! tivity "1#[ Examples of tri~uoromethyl transfer from the salts "0# are shown "Equations "54#Ð"56##[ The tri~uoromethylation of hydroquinone "Equation "55## e}ectively rules out a free radical process because hydroquinone is known to be an e.cient radical scavenger[ [Ar
H]
+
F3C
[ArHCF3]+ + L–
L
+
ArCF3 + H+ + L–
(64)
F2, CF3SO2OH
CF3I
0 °C
X–
XCF3 O2N
CF3SO2ONO2
NO2
+
+
X CF3 (1)
X
CF3SO2–
CF3 (2)
X = S, Se, Te Scheme 3
CF3
CF3
OH
+
i
(2) (X = S)
OH
OH (65)
+
52% i, DMF (+ 4-dimethylaminopyridine)
6%
OH
OH
+
(2) (X = S)
OH CF3
i
+
(CF3)2
OH 61%
OH
(66)
OH 11%
i, DMF (+ pyridine)
NH2
NH2
+ Reactant (1) (X = S) (2) (X = S)
(1) or (2) Conditions 80 °C, 1 h RT, 0.5 h
CF3
(67)
Products o-CF3 (31%) + p-CF3 (15%) o-CF3 (54%) + p-CF3 (20%)
5[90[1[1[3 Substitution of halogens by the tri~uoromethyl group acting as a nucleophile Tri~uoromethyllithium and !magnesium derivatives are unstable and\ therefore\ a methodology for the transfer of a tri~uoromethyl anion to electrophilic centres via silanes has been developed "Equation "57## ðB!81MI 590!90Ł[ A convenient synthesis of trimethyltri~uoromethylsilane has been
03
Trihalides
reported "Equation "58## ð79ZOB0786\ 73TL1084\ 82RHA121\ 81MI 590!91Ł\ and a process using tetra! kis"dimethylamino#ethene has also been described "Equation "69## ð78JFC"31#318Ł[ The key step involves displacement of the tri~uoromethyl group from silicon\ using tetrabutylammonium ~uoride "which inevitably contains amine#[ Understandably\ reaction only occurs with the more activated aromatic systems "Equations "60# and "61## ðB!81MI 590!92Ł[ CF3–
+
Ar
[ArLCF3]–
L
ArCF3 + L– PhCN
TMS-Cl + CF3Br + (Et3N)3P Me2N
NMe2
TMS-CF3
(69)
PhCN
+ TMS-Cl Me2N
(68)
TMS-CF3
(70)
or CH2Cl2
NMe2
NO2 F
+ TMS-CF3
tbaf, 0 °C, 0.5 h, RT
(71)
C6F5NO2 + CF3C6F4NO2 90%
10%
F NO2
+ TMS-CF3
tbaf, 0 °C, THF
mixture of trifluoromethylated products
(72)
NO2
5[90[1[1[4 Substitution of halogens by the tri~uoromethyl group using derivatives of metals As indicated above\ lithium and magnesium derivatives are unstable and\ therefore\ are not viable reagents for the introduction of the tri~uoromethyl group[ Metals that form weaker bonds to ~uorine generally give more stable tri~uoromethyl derivatives\ and consequently copper\ cadmium and zinc compounds are particularly useful in synthesis ð81T078\ 81T5444Ł[ Therefore\ access to tri~uoromethyl derivatives of these metals is of some importance[ Easily accessible sources for the e}ective use of the tri~uoromethyl moiety include CF2CO1H\ CF2SO1OH\ CF2I "usually made from tri~uoroacetic acid by Hunsdiecker processes#\ CF2Br and CF1Br1[ Tri~uoromethylation of aryl halides occurs using CF2I or CF2Br in the presence of copper powder in aprotic solvents at elevated temperatures "Equation "62## ð79JCS"P0#1644Ł\ but direct reaction of sodium tri~uoroacetate with CuI in N!methyl!1!pyrrolidone "NMP# is also possible ð70CL0608Ł\ and it has been concluded that the reaction proceeds via an intermediate like ðCF2CuIŁ=− rather than ðCF2CuIŁ = "Equations "63#Ð"65## ð77JCS"P0#810Ł[ Tri~uoromethanesulfonyl chloride can be used in an analogous way "Equation "66## ð78JFC"34#75Ł[ NH2
NH2 N
N
HMPA
N
N AcO
N
N
I
+
CF3Cu 46%
O
CF3 N
N AcO
AcO OAc
(73)
O
AcO OAc HMPA = hexamethylphosphoramide I
CF3 CF3CO2Na, Cu, NMP
(74) 160 °C, 4 h 98%
Cl
Cl
04
Tri~uoromethyl CF3
CF3
Br CF3CO2Na, Cu, NMP
+
(75)
160 °C, 4 h
Br
F3C
Br
CF3
CF3
48%
I
F3C
CF3CO2Na, Cu, NMP
N
41%
(76)
160 °C, 4 h 85%
Cl
N
Cl
Cl
CF3 NO2
NO2
Cu, DMF
+
(77)
CF3SO2Cl 100 °C 73%
NO2
NO2
A fascinating route to tri~uoromethylcadmium and !zinc has been developed by Burton and co! workers ð74JA4903Ł in which reaction of dihalodi~uoromethanes with cadmium or zinc powders in DMF gives stable solutions of the corresponding tri~uoromethyl derivatives "Scheme 3#\ which then react further[ Copper reacts in an analogous way but a mixture of homologues is obtained unless ~uoride ion is added\ or other procedures used to prevent the di~uorocarbene generated reacting further with CF2MX "Scheme 3#[ Cadmium derivatives can also be converted to copper reagents ð75JA721Ł\ and these can be stabilized against formation of higher homologues by adding HMPA ð78JA7491Ł "Equations "67# and "68##[ Tri~uoromethylation in dimethylacetamide "DMA# is also e.cient "Equation "79## ð77CC527Ł[ Transfer of the tri~uoromethyl group to amines\ using dibromo! di~uoromethane\ has also been reported ð80JFC"41#118Ł "Equation "70##[ Methyl ~uoro! sulfonyldi~uoroacetate in the presence of copper"I# iodide functions in a similar way ð78JCS"P0#1274Ł\ and the corresponding iodide has also been used "Equations "71# and "72##[ The source of the starting materials in the latter cases is tetra~uoroethene\ via formation and ring opening of a b! sulfone "Scheme 4# ð59JA5070Ł^ this is an attractively direct but\ unfortunately\ potentially hazardous process for laboratory application[
DMF, RT
CF2XY + M
[CF3MX + (CF3)2M] 80–95%
X = Br, Cl; Y = Br, Cl; M = Cd, Zn, Cu
MXY + [CF2]
F
DMF
Me2N
+
+ CO
Me2N
F
F– + [CF2]
CF3–
CF3– + MXY
CF3MX + (CF3)2M
CF3CuX + [CF2]
CF3CF2CuX
[CF2]
CuY
[CF3CdX + (CF3)2Cd]
[CF3Cu] –40 °C
90–100%
Y = I, Br, Cl, CN Scheme 4
etc.
F
F–
05
Trihalides I
CF3 DMF
NO2
+
NO2
CF3Cu
(78)
HMPA 70 °C, 4–6 h 75%
I
F3 C
I
+
CF3Cu
CF3
DMF
I
I
S
(79)
HMPA 70 °C
F3C
Cl
S
CF3
CF3 NO2
NO2
Cu, DMA
+
(80)
CF2Br2 100 °C, 4 h 93%
NO2
CF2Br2
NO2 Me2N
NMe2
Me2N
NMe2
+
+ R2NH
R2NCF3
I
CF3 CuI, DMF
+
FO2SCF2CO2Me
(81)
(82)
60–80 °C, 3 h 80%
NO2
NO2
ICF2SO2F +
Ph
F
Cu, DMF
Br
Ph
80 °C 83%
F
F
< 80 °C
+ F
SO3
F
~3 atm 93%
F F
F
(83)
F
F F
F–
FCOCF2SO2F
O SO2 Scheme 5
5[90[1[2 Derivatives of Alkanes\ Alkenes\ Alkynes and Other Saturated Compounds 5[90[1[2[0 Halogen exchange These reactions ð52AFC"2#070\ B!78MI 590!90\ 30JA2367\ 36JA0719Ł involve\ essentially\ the nucleophilic displacement of other halogens by ~uorine using a metal ~uoride ðB!62MI 590!90\ B!65MI 590!92Ł\ frequently in combination with hydrogen ~uoride[ An important part of the function of the metal ~uoride is to act as a Lewis acid\ to assist the removal of the halogen as a halide ion[ Some of the reactions could involve carbocations "Scheme 5#[ As the number of ~uorine atoms attached to the chlorine!bearing carbon increases\ it becomes progressively more di.cult to e}ect further ~uorination "Equation "73# and "Scheme 6##[ Never! theless\ the inhalation anaesthetic CF2CHBrCl may be obtained by an exchange process "Scheme 7# ð46BRP656668Ł[ For a carbocation!type process\ it is understandable that the introduction of unsaturated sites makes such exchange reactions much easier "Equations "74# ð30JA2367Ł and "75# ð36JA0719Ł#[ Fluorination of hexachlorobutadiene provides an accessible route to hexa~uoro!1! butyne "Equations "75# and "76## ð38JA187Ł[ Functional derivatives are also accessible by these procedures\ for example halo!ethers and !thioethers "Equation "77## ð41JA2483Ł as well as hexa! ~uoroacetone\ which is made commercially by this route "Equation "78## ð53FRP0258673Ł[ Antimony ~uorides and various other ~uorides have been used to promote exchange with hydrogen ~uoride\
06
Tri~uoromethyl [MFxCl]–
+
F– (HF)
Cl + MFx
F + MFx-1Cl
or
δ+
Cl
δ–
MFx-1 F Scheme 6
and very e.cient catalysts have been developed by industry\ including chromia catalysts for use in vapour phase processes^ these are particularly important in the refrigerant industry "see Section 5[90[0[2#[ HF, SbCl3, Cl2
CCl4
CCl3CCl3
CCl3CCl2F
(84)
CCl3F + CCl2F2 + CClF3
110 °C, 3 atm
9%
CCl2FCCl2F
90%
0.5%
CCl2FCClF2
CClF2CClF2
CF3CClF2
Scheme 7
HF, SbF5
CCl3Me
Br2
Cl2
CF3Me
CF3CH2Cl
CF3CHBrCl 425–475 °C
Scheme 8
Cl Cl
F
Cl Cl
SbF3
Cl F
F
F
Cl
+
F Cl
(85)
150 °C
Cl
Cl
Cl
Cl
Cl
43%
Cl
Cl
Cl
Cl Cl
Cl
SbF3Cl2
Cl
Cl Cl
Cl
F
F
F
F Cl
F
Cl
Cl
Cl
F
F
+
F
Cl
28%
Cl
Cl
F
F
F
F Cl
F
(86)
F
F
F
Cl Cl
Zn, Ac2O
F F
F
63%
F
F
F
F
F
F
(87)
07
Trihalides Cl Cl Cl
SbF3, SbCl5
SMe
Cl +
90 °C
F SMe
F
73%
Cl
SMe
(88)
F
O
O
Cl
Cl
Cl
Cl
Cl
Cl
HF, 350 °C Cr (cat.)
F
F
F
F
F
F
(89)
Alkali metal ~uorides\ although easily used\ have limited application for saturated sites "Equation "89## ð52JOC001Ł\ but such systems are extremely e}ective for attack at unsaturated sites "Equation "80##\ where even lithium ~uoride\ normally the least reactive of the alkali metal ~uorides\ can give some ~uorination "Equation "81## ð48JA1967\ 59JA2980Ł[ These reactions probably involve nucleo! philic attack with allylic rearrangement\ and other metal ~uorides will also promote this process "Equation "82## ð59BRP712408Ł[ Terminal ~uorinated alkenes are rearranged to the thermo! dynamically more stable isomers by the ~uoride ion "Equation "83## ðB!62MI 590!91Ł[ Furthermore\ hexa~uorobutadiene is converted into hexa~uoro!1!butyne by ~uoride ion "Equation "84## ð50JA0656Ł and\ more surprising\ hexa~uorocyclobutene also gives hexa~uoro!1!butyne when passed over hot caesium ~uoride or potassium ~uoride "Equation "85## ð68CC853Ł[ An even more remarkable rearrangement induced by hot metal ~uorides involves conversion of per~uorobicyclobutylidene to a product containing three tri~uoromethyl groups "Equation "86##[ Cl
Cl
Cl
Cl Cl
Cl
KF, 190 °C
F
Cl
NMP ~60%
F
Cl
Cl Cl
F
Cl F
F F
F LiF, cellosolve
F
Cl
F
F
90–95%
F
CsF, 100 °C
C4F9
F
no solvent
F
F
F
F
+
C4F9
F–
F–
F
+
F C3F7
F F
(94)
F
F
F
F F
F
F
F
+
F C4F9
F
F–
(93)
F
–
F
F
F
(92)
F
F
F
F
F
F HF, CoF2, 250 °C
Cl
F
F
F
Cl
F– +
(91)
F
F
F
(90)
Cl
F
90%
Cl Cl
F F
F
F
F
Cl
(C2H5)4NF, CHCl3 27 °C, 12 h
F
F
F
CsF, 100 °C, no solvent
F
F
F
F F
F
+ F–
(95)
08
Tri~uoromethyl F
F
i
F
F
F
80–90%
F
F
F
F
F
F
F
F
(96)
i, CsF or KF, 510–590 °C, flow system in N2
F
F F
i
F F
F
(97)
F
F
70%
F
F
F F
F
i, KF, 510 °C, flow system in N2
5[90[1[2[1 Conversions of other groups to the tri~uoromethyl group Use of sulfur tetra~uoride ð59JA432Ł to convert the carboxyl group to the tri~uoromethyl group proceeds well\ except where formation of anhydrides is in competition "Equations "87# and "88## ð67PJC60Ł and in some cases other functional groups present also react preferentially "Scheme 8# ðB! 78MI 590!91Ł[ Treatment of ~uorinated enols with DAST gives tri~uoromethyl derivatives with a high degree of regio! and stereoselectivity "Equation "099## ð80TL4852Ł[ An interesting in situ electrophilic formylation and subsequent reaction with sulfur tetra~uoride has been reported "Equa! tion "090## ð71ZOR117Ł[ HO2C
( )8
CO2H
HO2C
F
F
F ( )3
F
( )3
SF4, 120 °C, 6 h
F
87%
F
F
+
F
+
F
F
F F
O 10%
34%
F ( )8
F
(98)
F
SF4, 5 °C, 48 h
CO2H
F
F
F
F
F
F F
( )3
F
F ( )3
O
F
(99)
F
16% 100 °C
F
50%
F
HF, 20 °C
F
60%
F
F
F
F COF
O
+ SF4
CO2H
HO2C
F
F
F
F
F F
Scheme 9 Ph
F
F
Ph
+ Et2NSF3 OH
F
F
SF4, HCO2H, HF
F
(100)
(101) CF3
Although halogen exchange to form the tri~uoromethyl group proceeds well "see above#\ pro! cedures to convert the methyl group to the tri~uoromethyl moiety directly are limited[ High!valency metal ~uorides\ for example cobalt tri~uoride\ will carry out this conversion at high temperatures\
19
Trihalides
but the rest of the molecule is also ~uorinated in the process\ leading to very useful inert ~uids "Equation "091## ð59AFC"0#055Ł[ Various direct ~uorination procedures can also be used for such transformations "Equation "092## ðB!62MI 590!92Ł[ CF3 CoF3
(102) F
F
CF3 F2
(103) F
Au on Cu
CF3
Electrochemical ~uorination "ECF# is a procedure for converting C0H bonds to C0F bonds at the anode of an electrochemical cell during the electrolysis of hydrogen ~uoride ð56FCR66Ł under conditions that do not generate elemental ~uorine[ The process is operated on an industrial scale and is particularly e}ective for polar systems\ for example the synthesis of tri~uoromethanesulfonic acid "Scheme 09# and other functions "Equation "093# and Scheme 00#[ An interesting conversion of the amino group to the tri~uoromethyl group involves conversion to an azo derivative\ using nitrosotri~uoromethane\ followed by photolytic elimination of nitrogen "Scheme 01# ð66AG"E#743Ł[ ECF
MeSO2F
H2O
CF3SO2F
CF3SO2OH
96%
Scheme 10
ECF
CS2
CF3SF5
(104)
90%
ECF
MeCOF
H2O
CF3COF
CF3CO2H
Scheme 11
CF3 C8H17NH2 + CF3NO
N N C8H17
hν 69%
C8H17CF3
Scheme 12
5[90[1[2[2 Transfer of tri~uoromethyl groups as radicals One of the most e}ective and e.cient procedures for transferring tri~uoromethyl radicals involves the use of iodo! or bromotri~uoromethane for addition to an unsaturated unit "see Section 5[90[0[1#[ These are generally radical chain reactions\ and they proceed with very high e.ciency when a relatively nucleophilic centre is involved\ and a range of catalytic procedures have been developed\ as illustrated in Table 1[ Electrolysis of tri~uoroacetic acid is a very direct and attractive route for generation of tri~uoro! methyl radicals[ Mixed Kolbe processes lead to tri~uoromethyl derivatives by combination of radicals "Equation "094## ð64CJC418Ł\ although the process is not e.cient[ Similarly\ addition of tri~uoromethyl radicals\ generated this way\ to alkenes and derivatives leads to mixtures of products where dimerization of the radical arising from addition of the tri~uoromethyl group can be a signi_cant pathway "Equation "095## ð63CC212\ 67JCS"P0#191Ł[ Products that arise from cyclization of the intermediate radical "Equation "096## ð80T438Ł and from di!addition have been observed "Equa! tions "097# ð68CJC1506Ł and "098# ð78TL098Ł#[ Enzymes have been used to promote radical additions
10
Tri~uoromethyl Table 1 Addition of halo~uoromethanes to alkenes[
ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Yield Reactants Catalyst:conditions Product ")# Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Ru2"CO#01 CF2CH1CHISiMe2 78 73TL292 CH1 CHSiMe2 ¦CF2I CH2CO"CH1#7CH Et2B CH2OCO"CH1#7CHICH1CF2 75 78TL2048 CH1 ¦CF2I CH1 CHC5H02 ¦CF2Br NaSePh CF2CH1CH"SePh#C5H02 ¦ 15\ 23\ 20 80TL264\ 80TL6314 CF2SePh¦PhSeSePh Na1S1O3 NaHCO2 CF2CH1CHIR B!83MI 590!90 CH1 CHR¦CF2I CH1 CHR "R Ph\ Ru"PPh2#2Cl1 CF2CH1CHClR 78CC0448 CO1Et\ alkyl#¦CF2SO1Cl ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
"Equation "009## ð77JOC1249Ł\ and it is probable that these are reacting as electron transfer agents\ in the manner that various other transition metal systems behave[ Reactions of plasma!generated radicals can be very e.cient "Scheme 02# ð68CC017Ł[ F EtO2C
CO2H
electrolysis
F
EtO2C
+ CF3CO2H
electrolysis
+ CF3CO2H F
F
F
+ F
F major
F
F
F
+
F
(105)
F
46%
F
F
+
F
F (106)
F
F
F H N
electrolysis
+ CF3CO2H
F
F
F F
F
(107)
N H O NEt
electrolysis
F
40%
F
O
+ CF3CO2H
NEt F
O
F
electrolysis
CONH2
F
F
+ CF3CO2H
O
F
F
F
F
F (110)
39%
F
Ph F
CI4
plasma
CF3I
F
urease
Ph
(109)
CONH2
F CF3I +
F
F
35%
(108)
CF3• 97%
F3C F3C F3C
CF3 1
Scheme 13
F
+ :
F3C F3C F3C
I 3
11
Trihalides
5[90[1[2[3 Reactions involving tri~uoromethyl derivatives of metals and metalloids Electrophilic tri~uoromethylating agents "see Section 5[90[1[1[2# can be applied to transferring the tri~uoromethyl group to an alkyne "Equation "000## ð89TL2468Ł\ and acidic sites derived from alkyl pyridines may be tri~uoromethylated using tri~ic anhydride\ together with formation of corresponding tri~ates "Equation "001## ð72JOC0665Ł[
Ph
+
Li
+
Se CF3
Ph
46%
CF3SO2O–
(111)
CF3
CF3
+
(112)
+
(CF3SO2)2O N
N
CH2OSO2CF3
N 62%
5%
Nucleophilic tri~uoromethylation has been carried out directly with a system that is highly susceptible to nucleophilic attack "Equation "002## ð89IZV380Ł\ although the nature of the inter! mediate is not clear[ Displacement of the tri~uoromethyl group from trimethyltri~uoromethylsilane\ using the ~uoride ion "see Section 5[90[1[1[3#\ is applicable to a range of systems "Scheme 03# ðB! 81MI 590!90Ł\ and\ used in conjunction with copper"I# salts\ trimethyltri~uoromethylsilane functions as a tri~uoromethylcopper reagent which will tri~uoromethylate aryl\ benzyl and allyl halides "Equation "003## ð80TL80Ł[
F
F
F
F
F
F F
F
F
F F
+ CF3Br/P[NC2H5)2]3
CH2Cl2, –78 °C, argon
F
45%
F
F
F
TMS-O R1 F3C
F– THF
R1 = alkyl, aryl R2 = alkyl
F
F F
HO R1 F3C
HCl
CO2R2
F
F
F
F F
F
R1COCO2R2 + TMS-CF3
F
68–83%
(113)
F
CO2R2
Scheme 14 KF, Cu(I)
R1X + CF3SiR23
R1CF3
(114)
DMF, 60–80 °C 23–94%
Tri~uoromethylcopper reagents\ made by other routes\ react with various substrates "Equations "004# ð81CC42Ł\ "005# ð68TL3960Ł and "006# ð71CL0342Ł#\ and zinc reagents are also useful ð81T078Ł in a variety of contexts[ Cl Ph
Br
+ F
F–, CuI
PhCF3
CO2Me
Ph
Br
+ CuCF3
(115)
84%
F
HMPA (CF3I + Cu)
Ph
F
65%
F
F
(116)
12
Trichloromethyl OH
Zn, CuI
F
61%, (E):(Z) = 3:7
F
+ CF3I
(117)
OH F
5[90[2 TRICHLOROMETHYL DERIVATIVES*RCCl2 5[90[2[0 Trichloromethyl Groups Attached to an Aliphatic Centre Trichloromethyl compounds can be prepared either by converting an existing group into a trichloromethyl group or by introducing a trichloromethyl group on to a carbon atom in an existing molecule "see also Section 5[90[0#[
5[90[2[0[0 Conversion of groups attached to an aliphatic centre into the trichloromethyl group As with chloro~uorocarbons\ the manufacture of many chlorinated solvents is being phased out[ Of these\ only 0\0\0!trichloroethane is relevant to this chapter[ Several routes are available\ and the choice\ which makes use of permutations of chlorination\ hydrochlorination and dehydro! chlorination\ is outlined in Scheme 04[ Hydrochlorination is usually e}ected by Lewis acid catalysis "e[g[\ FeCl2#\ and dehydrochlorination by thermal cracking or by the action of base[ Chlorination is catalysed by free radical sources in the liquid or gas phase[ The route chosen depends in part on how much hydrogen chloride the operator is prepared to make[
H2C
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
CH2
Cl Cl Cl
Cl Cl
C2H6
Cl Scheme 15
5[90[2[0[1 Transfer of the trichloromethyl group to an aliphatic centre "i# Preparation of trichloromethylalkanes Trichloromethyl anions are an unstable species and decompose to give dichlorocarbenes[ However\ the problem of their instability can be minimized by running reactions at low temperature and by generating the trichloromethyl anion in the presence of the substrate[ Trichloro! methyllithium\ which can be made at about −099>C from trichloromethane and butyllithium in THF\ reacts successfully with iodoalkanes at this same temperature to give a series of trichloromethyl alkanes "Equation "007## ð89JOC0170Ł[ Cl R
I
BuLi, CHCl3, THF, –100 °C HMPA
R = –(CH2)nCH=CH2 (n = 2 or 3), –CH2
R
Cl Cl
(118)
13
Trihalides
The trichloromethylation of activated alkyl halides can also be carried out by a cross!coupling reaction with tetrachloromethane in an undivided electrochemical cell with a sacri_cial anode[ The preferred anode is zinc\ with a stainless steel cathode\ and the preferred solvent is a mixture of THF and tetramethyl urea "Scheme 05# ð77TL0588Ł[ Mn+ + ne–
M
Anode
Cathode
CCl4 + 2e–
CCl3– + Cl–
CCl3– + RX
CCl3R + X–
RX = PhCH2Br, MeCHClOCO2Et, BrCH2CO2Me, Me(CH2)9Br Scheme 16
Trichloromethylated compounds can also be prepared by the action of trichloromethyl anions generated by the action of a base on trichloromethane[ Thus\ by using catalytic amounts of electrochemically generated base\ a relatively stable anion is produced which reacts with a\b! unsaturated esters and nitriles to give the corresponding b!trichloromethyl adducts in good yield[ The base is made by the electroreduction of 1!pyrrolidone in DMF using tetraalkylammonium salts as supporting electrolytes "Scheme 06# ð89TL6070Ł[ +e–, 1.8 F mol–1
O
N H
R = Et, X = OTs; R =
CHCl3
–
N
DMF, R4NX Pt cathode
Bun,
–
X = BF4
R4
eg.
R4N+ CCl3–
O
N
2
R4N+
DMF
+
+ –1 H2
O
CO2Me CN
or
N+
Cl Cl
CO2Me
Cl or
Cl
Cl
CN Cl
Scheme 17
b!"Trichloromethyl#nitroalkanes can be prepared in good yield by the reaction between trichloro! methyl anions\ generated from trichloromethyltrimethylsilane and caesium ~uoride "see also 5[90[0[1#\ and nitroalkenes "Equation "008## ð80SC1078Ł[ R3
Cl
i, TMS-CCl3, CsF, THF, 25 °C
R1
NO2 R2
R3
R1
R2
Cl
ii, H+
R1 Bun Ph Me Et Me
Cl
R2 Me H H H Me
NO2
(119)
R3 H H Et H Me
Closely related to the trichloromethyl radical additions outlined in Section 5[90[0[1[2 is the reaction of trichloromethylsufonyl chloride with 0!alkenes in the presence of ruthenium complexes such as dichlorotris"triphenylphosphine#ruthenium"II#[ In this reaction\ the elements of CCl2 and chlorine are added to the double bond in high yield under mild conditions with the extrusion of sulfur dioxide ð72SUL020Ł[ When the chiral Ru2Cl3"diop#2 is the catalyst\ chiral adducts are obtained ð76BCJ2576Ł[
14
Trichloromethyl "ii# Preparation of a!trichloromethyl carbinols
a!Trichloromethyl carbinols are valuable intermediates for making compounds in which the trichloromethyl group is preserved and also for making those in which the trichloromethyl group has been transformed into other functions "e[g[\ ð60S020\ 71TL0598\ 77M0316\ 78S355\ 80RCR0207\ 81TL2324Ł#[ Essentially\ their preparation comprises the formation of a trichloromethyl anion followed by its attack on an aldehyde or ketone "Scheme 07#[ CCl3–
AcCl3 R1
O CCl3– +
R2 R1
R2
–O
Cl Cl Cl
R1 R2 HO
H+
Cl Cl Cl
Scheme 18
Carbonyl compounds have been treated successfully with trichloromethyllithium\ but because the reactions have to be carried out at −099>C\ only the more reactive carbonyls can be used ð53AG"E#402\ 56JOC0106\ 77M0316\ 89JOC0170Ł[ Reactions can be carried out at higher temperatures "−67>C# if lithium dicyclohexylamide is used to generate the trichloromethyllithium from trichloro! methane in the presence of the carbonyl "Equations "019#Ð"012##[ Equation "012# gives equally good results with tribromomethane in place of trichloromethane ð63JA2909Ł[ i
Ph2CO
Ph2COHCCl3
(120)
ii
i, BunLi, CHCl3, –110 °C, THF/Et2O, petroleum ether; ii, H+ i, BunLi, CHCl3, –100 °C, THF
(CF3)2CO
R
( )n
CHO
(CF3)2COHCCl3
ii, H+
i, BunLi, CHCl3, –100 °C, HMPA
R
COHCCl3 ( )n
(121)
(122)
ii, H+
R H H Me O
n 2 3 2 HO
CCl3
i
(123)
i, Lithium dicyclohexylamide, CHCl3, –78 °C, THF, hexane
Trichloromethane and a base have been used extensively to generate the trichloromethyl anion[ The base may be sodium or potassium hydroxide ð33JCS63\ 49JA4901\ 72M702\ 76JOC833Ł\ an alkali metal alkoxide ð47CB1553\ 53JOC0037Ł\ or potassium ~uoride supported on alumina ð75TL2734Ł[ The amount of base\ its nature and also the choice of solvent are particularly important when the carbonyl compound is inclined to undergo an aldol condensation or the Cannizzaro reaction[ Reactions are generally carried out below 9>C to help suppress dichlorocarbene formation[ Phase transfer catalysts have been used in these reactions\ but they were only really successful with higher aldehydes and ketones ð79JOC4103\ 68TL0362Ł[ The thermal decomposition of sodium trichloroacetate in a solvent yields dichlorocarbene ð48PCS118Ł[ However\ the intermediate trichloromethyl anion can be trapped by aldehydes to yield trichloromethyl carbinols[ Under similar conditions\ anhydrides react to give trichloromethyl lactols or their tautomeric keto acids "Equation "013## ð56JOC1055Ł[ Trichloromethyl carbinols are also obtained in high yield when\ in the presence of an aldehyde\ trichloroacetic acid decomposes in DMSO ð72CC172\ 73JCS"P1#0136\ 78JCS"P1#140Ł or HMPA ð89S216Ł\ or a 0 ] 0 mixture of the trichloro!
15
Trihalides
acetic acid and its sodium salt decomposes in DMF ð81TL2324Ł[ These reactions are successful with aliphatic as well as aromatic aldehydes[ They are less successful with ketones unless the ketone is "partially# ~uorinated and therefore more electrophilic\ in which case the yields are high ð81BAU269Ł[ O
O
HO
O
CCl3
CCl3
CCl3CO2Na
O
OH
DME
O
(124)
O
O
Trichloromethyl compounds of silicon and tin have been used as sources of trichloromethyl anions in reactions with carbonyl compounds[ For example\ the reaction of trichloro! methyltrimethylsilane and trimethylsilyl trichloroacetate in the presence of the ~uoride ion with aromatic and aliphatic aldehydes ð74JA3974\ 76SC0936\ 77T3024Ł\ trimethylsilyl trichloroacetate in the presence of potassium carbonate and 07!crown!5 with aromatic aldehydes and ketones ð74TL0064Ł\ and tributyl"trichloromethyl#stannane with aliphatic and aromatic aldehydes ð64JOM"091#312Ł all give the corresponding trichloromethylcarbinols in good yield "Equations "014#Ð"017##[ Equation "017# proceeds with equal success to give tribromomethylcarbinols when tribromomethyltributyltin is used instead of the trichloromethyl tin compound[ R
i, TMS-CCl3, tas-F, THF, 0 °C
Cl Cl Cl
RCHO ii, H+
HO
(125)
R = Ph, n-C10H21, PhCH(Me); tas = tris(diethylamino)sulfonium
R1 O
i, CCl3CO2-TMS, F–, THF
R1
ii, H+
R2
Cl Cl Cl
HO R2
(126)
F = KF or tas-F R1 O = cyclohexanone, benzaldehyde, pivaldehyde, 2-cyclohexenone, crotonaldehyde R2 R1 O
i, CCl3CO2-TMS, K2CO3, 18-crown-6
R1 HO
ii, H+
R2
R2
Cl Cl Cl
(127)
R1 R2
O = e.g. benzaldehyde, 3,5-dichlorobenzaldehyde, 4-hydroxybenzaldehyde, cyclobutanone, cyclopentanone, cyclohexanone
RCHO
i, Bu3SnCCl3, 80 °C ii, H+
R HO
Cl Cl Cl
(128)
R = Me, Et, Pri, Ph, PhCH = CH
The reductive addition of tetrachloromethane to aldehydes using a lead:aluminum bimetal redox system has been reported to give high yields of trihalocarbinols[ While a variety of aliphatic and aromatic aldehydes give good yields\ ketones give less satisfactory results[ The use of bromo! trichloromethane instead of tetrachloromethane gives exclusively the same product "Scheme 08# ð78JOC333Ł[ A variety of aldehydes have been treated with trichloromethyl anions generated by the cathodic reduction of tetrachloromethane in trichloromethane[ Only relatively small amounts of tetra! chloromethane are used in this reaction\ since it is the trichloromethane which supplies the proton to the intermediate anion and thereby generates another trichloromethyl anion*steps "ii# and "iii# in Scheme 19[ The use of vinyl acetate instead of an aldehyde yields the acetate MeCH"OAc#CCl2 ð70TL760\ 71TL0598\ 71TL3790Ł[ These same workers oxidized trichloromethyl carbinols with chromic oxide to give the corresponding trichloromethyl ketones ð71TL0598Ł[
16
Trichloromethyl R
X
HO
X
PbX2 (cat.)/Al, DMF
RCHO + CX4
Pb(0)
Pb(II)
Al(III)
Al(0)
X
X = Cl or Br; R = alkyl, aryl Scheme 19
+2e–
CCl4
CCl3– + Cl– –O
Cl Cl Cl
CCl3– + RCHO R –O
HO
Cl Cl + CHCl3 Cl
R
Cl Cl Cl
R
(i)
(ii)
+ CCl3–
(iii)
Scheme 20
The other approach to making trichloromethyl carbinols is to start with trichloroacetaldehyde "chloral#[ This compound will condense with aromatic hydrocarbons with FriedelÐCraft catalysts "e[g[\ H1SO3\ HCl\ AlCl2\ BF2 and ZnCl1# ð12CB868\ 31JA1404\ 55CJC464\ 57CJC1122\ 79CJC374Ł or under the in~uence of basic catalysts "e[g[\ potassium hydroxide\ potassium carbonate and pyridine# ð45CB1467\ 14JPR014\ 41CB890Ł to yield trichloromethyl carbinols[ Certain Grignard reagents will react with chloral to give trichloromethyl carbinols\ although reduction of the chloral to trichloroethanol can be a problem "Equation "018## ð40M0997\ 45BSF0330Ł[ Finally\ silanes\ R!TMS\ in which the group R is electron!withdrawing\ have been shown to react with chloral in the presence of a Lewis acid to give the corresponding trichloromethyl carbinols "Scheme 10# ð64JOM"82#32Ł[ RMgBr
R-TMS
+
Cl Cl Cl
CHO
+
Cl Cl Cl
R CHO HO R
Al, Ga or InCl3
TMS-O
Cl Cl Cl
Cl Cl Cl MeOH
(129)
R HO
Cl Cl Cl
R = allyl, aryl, vinyl, ethynyl, propargyl Scheme 21
5[90[2[1 Trichloromethyl Groups Attached to an Aromatic Ring The high reactivity of trichloromethylarenes makes them valuable intermediates in the synthesis of acids and their derivatives\ heterocyclic compounds and the tri~uoromethyl group "which we have seen is of great interest to the pharmaceutical and agrochemical industries#[ Similarly to trichloromethyl aliphatic compounds\ trichloromethylarenes may be made by converting a group which is already attached to a ring into a trichloromethyl group or by transferring a trichloromethyl group on to a ring[
17
Trihalides
5[90[2[1[0 Conversion of groups attached to an aromatic ring into the trichloromethyl group Methyl groups in arenes can be trichlorinated using chlorine\ by a free radical mechanism "Equation "029## ð51HOU"4:2#624Ł[ 1! and 3!Methylpyridines and 1! and 3!methylquinolines are also readily trichlorinated\ but here reactions are best carried out by passing the halogen into a solution of the substrate in glacial acetic acid\ optionally acetic anhydride\ and sodium or potassium acetate\ where the reaction is believed to proceed by an ionic process\ with the acetate acting as a base ð12JCS1771\ 28JCS670\ 40JCS0034Ł[ 2!Methylpyridine cannot be trichlorinated by this method\ but when its vapour and chlorine are passed over a chromia catalyst\ pretreated with hydrogen ~uoride\ 2! trichloromethylpyridine is produced ð71EUP54247Ł in reasonable yield[ CCl3 Cl2
(130)
heat or UV
While these methods are fairly general\ there are situations where other methods are necessary^ for example\ in the preparation of methylbenzotrichlorides where chlorination of dimethyl com! pounds leads to chlorination in both side chains\ and in the preparation of compounds such as 3!nitrobenzotrichloride where the electron!withdrawing group inhibits chlorination[ Thus\ car! boxylic acid groups in aromatic and heteroaromatic rings are converted into trichloromethyl groups by treatment with phosphorus pentachloride in thionyl chloride ð66JHC770\ 67JHC782Ł\ or with phosphorus pentachloride alone ð78JCS"P0#172Ł[ This conversion can also be accomplished by treating acids with chlorine in a mixture of phosphorus trichloride and phenylphosphonic dichloride ð72USP3308403Ł or phenyl dichlorophosphorane and phenylphosphonic dichloride ð78USP3722149Ł[ Substituted benzal chlorides\ which can be prepared from the corresponding aldehydes ð67JOC3256Ł\ can be chlorinated further to trichloromethyl compounds by treatment with isobutyl hypochlorite in aqueous sodium hydroxide\ optionally in the presence of an alcohol\ and a phase transfer agent ð67USP3987720Ł[ Substituted benzyl and benzal chlorides are also converted into the corresponding benzotrichlorides when they are treated with tetrachloromethane or hexachloroethane and aqueous sodium hydroxide in the presence of a phase transfer catalyst "PTC# by a process which probably involves nucleophilic attack on chlorine "Equation "020## ð75S113Ł[ Cl
X
CCl3 CCl4 or CCl3CCl3
(131)
50% aqueous , NaOH, PTC, reflux
R R X = H; R = 2-NO2, 2-NO2, 3-Me X = Cl; R = 2-NO2, 2-NO2, 3-Me, 2-Me, 3-Me, 4-Me, 2-Me, 2-Cl, 4-Et
A similar range of compounds is made by treating appropriate dibenzyl sulphides with chlorine or sulfuryl chloride "Equation "021## ð71S840Ł^ or by chlorinating with sulfuryl chloride the product obtained from treating an aldehyde with a dithiol in the presence of acid "Scheme 11# ð75USP3464454Ł[ Dichlorine monoxide can be used to chlorinate methyl groups in methylnitrobenzenes and other methylbenzenes which have electron!withdrawing groups on the aromatic ring "Equation "022## ðB! 71MI 590!91Ł[ While 3!nitrotoluene and highly deactivated compounds such as 1!chloro!3!nitro!\ 2\3! dinitro! and 2\4!dinitrotoluene are converted into the corresponding benzotrichlorides in very high yield\ 1!nitrotoluene is only dichlorinated by dichlorine monoxide to give the benzal chloride[ "NB[ This compound could be chlorinated further by methods outlined above[# In the case of the other substituted toluenes with deactivating groups in the 3 position\ chlorination takes place exclusively in the methyl group with the exception of p!toluenesulfonic acid\ which undergoes chlorination on the ring[ R
R
R
Cl2 or SO2Cl2
2 S
CCl4, POCl3 or o-dichlorobenzene
R = 2-Mea, 3-Meb,c, 4-Mea, 2-Bra, 4-NO2d,e, 2,3-CH=CH–CH=CHa aCl2/CCl4, bCl2, cSO2Cl2/CCl4, dCl2/POCl3, eCl2/o-dichlorobenzene
CCl3
(132)
18
Trichloromethyl R
S ( ) n S
R
CHO
HS
( )n
SH
R SO2Cl2
HCl in CHCl3
CCl3
CCl4
R = 3-Me, 4-NO2, 2-Cl, 4-MeO; n = 2 or 3 Scheme 22 NO2 2
NO2
+ 3Cl2O
CCl4
2
+ 3H2O
(133)
CCl3
5[90[2[1[1 Transfer of the trichloromethyl group to an aromatic ring Aromatic compounds can be trichloromethylated by reaction with tetrachloromethane in the presence of excess Lewis acid\ which is most commonly aluminum trichloride "e[g[\ ð76JPR0020Ł#[ Whilst the trichloromethyl compounds can be the main product\ diaryldichloromethanes are also produced in signi_cant amounts "Equation "023##\ although it is claimed that the addition of mordenite can reduce dimer formation ð81JAP93038032Ł[ The reaction is fairly general\ but there are complications when polymethyl aromatics are trichloromethylated[ Thus\ while m!xylene gives the expected 1\3!dimethyltrichloromethylbenzene\ a Jacobson!type rearrangement occurs in the reaction with p!xylene to give 1\3!dimethyltrichloromethylbenzene as the main product "o!xylene gives no trichloromethyl compounds but yields the dichloromethane\ "2\3!Me1C5H2#1CCl1# ð78CS70Ł[ Similarly\ the trichloromethylation of mesitylene gives the expected product ð50JA3359Ł\ but during the trichloromethylation of pseudocumene ð78CS70Ł both the expected 1\3\4!trimethyltrichloro! methylbenzene and about 04) of the rearranged 1\3\5 isomer are produced "Scheme 12#[ Although mesitylene itself gives only the expected trichloromethylmesitylene\ 0\2\4!trimethylhalobenzenes give signi_cant amounts of the rearranged product "Scheme 13^ in this scheme the products were isolated as the corresponding methyl benzoates# ð69JOC2526Ł[ In the case of the tetramethylbenzenes "Scheme 14#\ durene gives almost exclusively the rearranged product\ 1\2\3\4!tetramethyltrichloromethyl! benzene "a small amount of disproportionation took place under the conditions used#\ whereas isodurene gives predominantly 1\2\3\5!tetramethyltrichloromethylbenzene\ some of the 1\2\3\4 iso! mer and a trace of the 1\2\4\5 isomer ð50JA3359Ł[ It was suggested that rearranged products in these reactions could arise by the trichloromethyl group attacking a ring carbon that is already substituted followed by a 0\1!methyl migration and proton loss\ but rearrangements induced by acid\ HCl:AlCl2\ are also possible[ Cl CCl4, AlCl3
CCl3
+
(134)
CCl3 CCl4, AlCl3 100%
mesitylene
CCl4, AlCl3 15% CCl4, AlCl3 85%
pseudocumene Scheme 23
Cl
CCl3
29
Trihalides X
X
X AlCl3, CCl4
+ CCl3 CCl3
X H F Cl Br
100 70 88 93
: : : :
0 30 12 7
Scheme 24
CCl3 CCl4, AlCl3
durene
CCl4, AlCl3 23%
CCl3
CCl4, AlCl3 2% CCl4, AlCl3
isodurene
73%
CCl3
Scheme 25
Highly chlorinated trichloromethyl and tri~uoromethyl aromatics are quite di.cult to prepare\ but Castaner et al[ ð80JOC092Ł found that treatment of polychlorinated benzenes with aluminum trichloride and ~uorotrichloromethane gives the tri~uoromethyl compound[ Treatment of this with more aluminum trichloride in carbon disul_de yields the corresponding trichloromethyl compound[ This reaction is reversed by treating the trichloromethyl compound with aluminum trichloride and ~uorotrichloromethane[ Bis"trichloromethyl# and bis"tri~uoromethyl# compounds were also made by these methods "Scheme 15#[ CF3 Cl
CCl3F, AlCl3
Cl
Cl3 AlCl3, CS2
Cl
CCl3F, AlCl3
Scheme 26
Trichloromethyl anions can be used to prepare trichloromethylated aromatics ð89TL5720\ In a one!pot reaction sequence\ a cyclopentadieneyliron!complexed arene is added to a solution made from potassium t!butoxide and chloroform in THF at −67>C[ The mixture is allowed to warm to room temperature\ and the intermediate is demetallated in situ with iodine to give the trichloromethylarene in good yield "Scheme 16#[ Aromatic compounds that are susceptible to nucleophilic attack\ such as 0\2\4!trinitrobenzene\ can be trichloromethylated by reaction with trichloromethyl anions generated by the decomposition of trichloroacetic acid in DMSO[ The _rst step is the formation of the Meisenheimer complex\ which is then oxidized to give the trichloromethylated product "Scheme 17# ð72CC039\ 73JCS"P1#0128Ł[ 80JOM"308#246Ł[
20
Tribromomethyl Cl3C R1
R1 HCCl3, ButOK
H
R1
CCl3
I2
–78 °C, THF
R2
R2
FeCpPF6
FeCp
R2
R1 Me Me Me H NO2 H Cl
R2 2-Me 3-Me 4-Me p-TolSO2 4-Me But 4-Cl indane tetralin benzosuberane Scheme 27
Similarly\ hexachloroacetone can be used as the source of trichloromethyl anions[ The decompo! sition of hexachloroacetone in DMSO is slower than that of trichloroacetic acid\ but it is accelerated by the addition of water[ It is believed that it is actually the hexachloroacetone hydrate that decomposes into the trichloromethyl anion\ and trichloroacetic acid which in turn decomposes to generate a second trichloromethyl anion ð75JCS"P1#360Ł CCl3 NO2
O2N
CCl3CO2H
CCl3 NO2
O2N
NO2
O2N
–
DMSO
NO2
NO2
NO2
Scheme 28
5[90[3 TRIBROMOMETHYL DERIVATIVES*RBr2 Considerably less work has been carried out on making compounds bearing a tribromomethyl group than on those bearing a trichloromethyl group[ With few exceptions\ the essentials of the methods for making tribromomethyl compounds are the same as those for making the trichloro! methyl analogues[ Thus\ tribromomethyl carbinols are produced when cyclohexanone is treated with tribromomethyl lithium at −67>C in THF ð63JA2909Ł\ or when various 2!pyridyl ketones are reacted at −099>C ð77M0316Ł[ Corresponding to the decarboxylation of trichloroacetic acid and its sodium salt to give the trichloromethyl anion is the decarboxylation of the analogous tribromo compounds[ The main di}erence between the two systems is that the tribromo compounds are less stable[ Thus\ tribromo! methyl carbinols are obtained when sodium tribromoacetate decomposes in the presence of alde! hydes[ In a similar reaction\ anhydrides react to give tribromolactols or their tautomeric keto acids ð56JOC1055Ł[ Tribromomethyl carbinols are also obtained when\ in the presence of aldehydes\ tribromoacetic acid decarboxylates in DMSO ð72CC172\ 73JCS"P1#0136Ł\ or a mixture of the acid and its sodium salt decarboxylates in DMF ð81TL2324Ł[ Again corresponding to the trichloromethyl case\ the reaction between tributyl"tribromo! methyl#stannane and an aldehyde gives a tribromomethyl carbinol[ The main di}erence between the two reactions is that tribromomethylation is exothermic at room temperature whereas trichloro! methylation requires some heating ð64JOM"091#312Ł[ Finally\ tribromomethyl carbinols can be made by the reductive addition of tetrabromomethane to aldehydes using a lead:aluminum bimetal system ð78JOC333Ł[
21
Trihalides
5[90[4 MIXED SYSTEMS WITH FLUORINE*RCF1Hal Per~uoroalkyl iodides*CnF1n¦0I*are some of the most important intermediates in the prep! aration of compounds which bear the per~uoroalkyl group "e[g[\ ð73JFC"14#58\ 77MI 590!90Ł#[ Some methods for the preparation of these compounds have been described previously "see Sections 5[90[0[0 and 5[90[0[1[1#\ but there are others which need to be noted[ Most of these methods take a per~uorocarboxylic acid as their starting point[ For example\ the thermal decomposition of the acid in the presence of iodine ð42USP1536822Ł\ the decomposition of per~uoroacyl chlorides in the presence of potassium iodide at 199>C ð47JOC1905Ł\ the decomposition of per~uoroacyl anhydrides in the presence of iodine at 249Ð399>C ð46BRP646782Ł and the thermal decomposition of dry metal salts in the presence of iodine all give per~uoroalkyl iodides[ Sodium\ potassium\ barium\ mercury and lead salts have all been used in this last reaction\ but it is silver salts which give the best yields ð40JCS473\ 41JA737\ 41JA738Ł[ This is known as the Hunsdiecker reaction\ and it can also be used to obtain {dihalides| from the corresponding diacid salts\ although lactone formation can be a problem ð41JA737\ 41JA0863Ł[ More recently\ it has been shown that treatment of sodium and potassium salts of per~uorocarboxylic acids with iodine in re~uxing DMF gives per~uoroalkyl iodides in high yield ð56JOC722Ł[ One compound in this class which has attracted a lot of interest of late is per~uorooctyl bromide "PFOB# because of its potential use as a contrast agent for diagnostic imaging[ The telomerization reaction between bromopenta~uoroethane and tetra~uoroethylene does not a}ord a convenient route to PFOB because the propagation step is so much faster than chain transfer\ and a mixture of high telomers is obtained[ Most of the practical routes for the manufacture of PFOB start from per~uorooctyl iodide\ which of course is manufactured on a substantial scale\ and replace the iodine by bromine[ For example\ iodides can be treated with bromine in the vapour phase at 299Ð249>C ð80EUP349473\ 81EUP404147Ł\ or with ultraviolet irradiation for 09 h ð73MI 590!90Ł[ Also\ PFOB can be made by re~uxing per~uorooctyl iodide with tetraalkylphosphonium bromide ð81GEP3914116Ł\ or with sodium bromide ð80GEP2826456Ł in DMF "a certain amount of reduction to the monohydro compound occurs here#\ and by heating with metal "Cs\ Mn"II#\ Fe"II# Fe"III# or Co"II## bromides to 299>C in an autoclave ð80EUP350452Ł[
5[90[5 MIXED HALOFORMS*CHXY1 AND CHXYZ Most methods for the preparation of mixed haloforms take the simple haloforms and replace one or two of the original halogens by others[ Trichloromethane "chloroform# is ~uorinated on an industrial scale in the liquid phase using Swarts| catalyst or in the vapour phase using chromia! based catalysts with hydrogen ~uoride as the ~uorinating agent "see also Section 5[90[0[2#[ The compound of greatest interest to the manufacturer is chlorodi~uoromethane\ since it is used in the manufacture of tetra~uoroethene\ but dichloro~uoromethane can also be made by this method[ Similarly\ tribromomethane "bromoform# can be ~uorinated using antimony tri~uoride and bromine ð54BRP0903141Ł\ or a ~uoride!type ion exchange resin ð51NKZ825Ł\ to give dibromo~uoromethane "Equation "024##[ CHBr3
i, ii
CHBr2F
(135)
i, SbF3, Br2, reflux; ii, amberlite IRA-400 (F type), 80 °C
Chloroform\ bromoform and iodoform can all be treated with an alkali metal halide and a base in the presence of a phase transfer agent to give mixed haloforms "e[g[\ Equations "025#Ð"039## ð78LA076\ 76TL1658Ł\ but satisfactory yields are not always obtained[ A single iodine in iodoform can be replaced by bromine simply by stirring a mixture of iodoform and bromine in tetrachloromethane for some 04 h "Equation "030## ð71CB2783Ł[ NaBr, NaOH, PTC
CHCl3
CHCl3
NaI, NaOH, PTC
CHBrCl2
(136)
CHCl2I + CHClI2
(137)
22
Mixed Haloforms NaCl, NaOH, PTC
CHBr3 NaI, NaOH, PTC
CHBr3
NaCl, NaOH, PTC
CHI3 CHI3
Br2, CCl4
CHBr2Cl
(138)
CHBr2I
(139)
CHClI2 + CHCl2I
(140)
CHBrI2
(141)
Dibromochloromethane reacts with sodium iodide and sodium methoxide in methanol to give bromochloroiodomethane "Equation "031## ð47JA3171Ł\ and with mercuric ~uoride to give bromo! chloro~uoromethane "Equation "032## ð45JA368\ 74JA5882Ł[ Bromochloro~uoromethane having high optical purity has been made by pyrolysing the optically pure strychnine salt of bromochloro! ~uoroacetic acid ð78JA7409Ł[ NaI, NaOH, MeONa
CHBr2Cl
CHBr2Cl
CHBrClI HgF2
CHBrClF
(142)
(143)
The thermal decarboxylation of silver salts of halogenated acetic acids in the presence of a halogen "the Hunsdiecker reaction*see Section 5[90[4# has been used to make the haloforms CHCl1F\ CHClF1\ CHClBrF\ CHClFI\ CHBr1F\ CHBrFI\ CHFI1\ CHBrF1 and CHF1I "e[g[\ Equations "033# and "034## ð41JCS3148Ł[
Copyright
#
CHF2CO2Ag + I2
CHF2I
(144)
CHClFCO2Ag + Br2
CHClBrF
(145)
1995, Elsevier Ltd. All R ights Reserved
Comprehensive Organic Functional Group Transformations
6.02 Functions Containing Halogens and Any Other Elements GRAHAM B. JONES and JUDE E. MATTHEWS Clemson University, SC, USA 5[91[0 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN 5[91[0[0 Halo`en and Oxy`en Derivatives "R0CHal1OR1 and R0CHal"OR1#1# 5[91[0[0[0 Tetracoordinated carbon atoms with two identical halo`en and one oxy`en function attached "R0CHal1OR1# 5[91[0[0[1 Tetracoordinated carbon atoms bearin` mixed halo`ens and one oxy`en function "R0CHal1OR1# 5[91[0[0[2 Tetracoordinated carbon atoms bearin` one halo`en and two oxy`en functions "R0CHal"OR#11# 5[91[0[1 Halo`en and Sulfur Derivatives "R0CHal1SR1 and R0CHal"SR1#1# 5[91[0[1[0 Tetracoordinated carbon atoms with two identical halo`en and one sulfur function attached "R0CHal1SR1# 5[91[0[1[1 Tetracoordinated carbon atoms bearin` mixed halo`ens and one sulfur function "R0CHal1SR1# 5[91[0[1[2 Tetracoordinated carbon atoms bearin` one halo`en and two sulfur functions "R0CHal"SR1#1# 5[91[0[2 Halo`en and Se or Te Derivatives "R0CHal1SeR1 or R0CHal1TeR1# 5[91[0[2[0 Tetracoordinated carbon atoms bearin` two halo`ens and one selenium function "R0CHal1SeR1# 5[91[0[2[1 Tetracoordinated carbon atoms bearin` two halo`en and one tellurium function "R0CHal1TeR1# 5[91[0[3 Halo`en and Mixed Chalco`en Derivatives "R0CHal"OR1#"SR2## 5[91[1 FUNCTIONS CONTAINING HALOGEN AND A GROUP 04 ELEMENT AND POSSIBLY A CHALCOGEN 5[91[1[0 Halo`en and Nitro`en Derivatives] General Considerations 5[91[1[0[0 Tetracoordinate carbon atoms bearin` two halo`ens and one nitro`en function 5[91[1[0[1 Tetracoordinate carbon atoms bearin` one halo`en and two nitro`en functions 5[91[1[0[2 Tetracoordinate carbon atoms bearin` one halo`en\ one nitro`en and one oxy`en function 5[91[1[0[3 Tetracoordinate carbon atoms bearin` one halo`en\ one nitro`en and one sulfur function 5[91[1[1 Halo`en and Phosphorus Derivatives 5[91[1[1[0 Tetracoordinate carbon atoms bearin` two halo`en and one phosphorus function and one halo`en and two phosphorus functions 5[91[1[2 Halo`en and Arsenic Derivatives 5[91[1[2[0 Tetracoordinate carbon atoms bearin` two halo`ens and one arsenic function 5[91[2 FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLY A CHALCOGEN AND:OR GROUP 04 ELEMENT
25 25 25 32 32 33 33 36 37 38 38 38 49 49 49 40 44 46 46 47 47 59 59 59 59 50 51
5[91[2[0 Halo`en and Silicon Derivatives 5[91[2[1 Halo`en and Boron Derivatives 5[91[2[2 Halo`en and Germanium Derivatives 5[91[3 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP 04 ELEMENT\ A CHALCOGEN OR A METALLOID
51 51 52 52
5[91[3[0 Halo`en and Lithium Derivatives 5[91[3[1 Halo`en and Ma`nesium Derivatives 5[91[3[2 Halo`en and Copper Derivatives
24
25
Halo`ens and any other Elements 5[91[3[3 5[91[3[4 5[91[3[5 5[91[3[6 5[91[3[7 5[91[3[8
52 53 53 53 54 54
Halo`en and Silver Derivatives Halo`en and Zinc Derivatives Halo`en and Cadmium Derivatives Halo`en and Mercury Derivatives Halo`en and Tin Derivatives Halo`en and Lead Derivatives
5[91[0 FUNCTIONS CONTAINING HALOGEN AND A CHALCOGEN A general review on ortho!ester derivatives covering the literature up to 0873 has been published ð74HOU"E4#Ł and provides a broad overview of several categories of haloalkyl systems relevant to this chapter[
5[91[0[0 Halogen and Oxygen Derivatives "R0CHal1OR1 and R0CHal"OR1#1# 5[91[0[0[0 Tetracoordinated carbon atoms with two identical halogen and one oxygen function attached "R0CHal1OR1# "i# From ethers Direct halogenation of ethers has proved a versatile technique for the synthesis of a variety of perhalogenated compounds of this class[ Novel per~uorinated ethers have been obtained by direct ~uorination of low molecular weight ethers with product ratios a function of the ~ow rate of ~uorine and carrier gas "usually helium# "Scheme 0# ð62JOC2506Ł[ The method has also been applied successfully to the preparation of per~uorinated polymers\ although in these cases the mixtures required heating up to 009>C for e.cient conversion ð66CC148\ 70JCS"P0#0210Ł[ Electrochemical ~uorination has also been investigated\ but it was found that\ under the optimum conditions used\ primary alcohols were converted into cyclic per~uorinated ethers in only moderate yield "Equation "0## ð65BCJ0777Ł[ The electrochemical ~uorination of ethylene glycol ethers has also been reported\ yielding complex mixtures of linear and cyclic per~uorinated compounds ð63ZOR1920Ł[
Me
Me
O
O
O
O
O
Me
F
20 ml/min He, 0.5 ml/min F2, –78 °C, 12 h
F3C
21%
O
F
F3C
16%
CF3
F F
20 ml/min He, 0.5 ml/min F2, –40 °C
Me
F
O
F
FF
O
O
O
F
F
F
CF3
F
Scheme 1
F F OH
HF, 3.5 A/1; 5 °C, 0–10 V
F F
F F
18%
F
O
(1)
CF3
Photochlorination of mixed halogenated ethers has been used in the synthesis of a number of anaesthetic agents "Scheme 1#[ Yields of the chlorinated systems are moderate to good\ reactivity being a function of carbon substitution patterns\ with monochlorinated carbon atoms being more reactive than the corresponding ~uoro!substituted carbons as expected ð41JA1181\ 60JMC406\ 60JMC482Ł[ Fluorination via direct substitution of chloro ethers has been accomplished using either HF or HF in the presence of SbF2 "Equation "1##[ Selectivity can be achieved by controlling HF introduction\ monitoring the progress of the substitution reaction by the HCl liberated ð60JMC482Ł[ Halogenation of heterocycles is a well!studied route to compounds of this class with trisubstituted
26
Halo`en and a Chalco`en
carbon atoms[ Electrochemical ~uorination of a range of oxanes gave the corresponding per! ~uorinated systems in moderate yield "Equation "2## ð68JFC"02#408\ 68JFC"04#242Ł[ F Cl
O
F
F
Cl F
Cl2, hν
F
80%
Cl
F F
O F Cl
Cl2, hν
F3C
O
Cl
Cl
F3C
80%
F O
F
F3C
75%
Cl
Cl F
Cl
Cl2, hν
F 3C
O
O
F Cl
Cl2, hν
F3C
O
Me 60%
F 3C
O
Cl
Scheme 2
CF3 F3C
Cl
O
CF3
HF, SbCl5, 0 °C, 12 min
Cl
or SbF3, SbCl5, 53 °C, 3 h 62%
F3C
O
electrochemical fluorination, HF 5.0–6.2 V, 3.5 A/dm2, 7 h
O
F
(3)
F
R
O
(2) F
Rf
R = Me, 28%; Et, 26%; Prn, 30%; Pri, 23%; Bun, 30%; Amn, 23%
Direct ~uorination of dioxane using elemental ~uorine is reported to give the per~uorinated system in moderate yield "Scheme 2# ð64JOC2160Ł\ whereas treatment with a mixture of sulfur tetra~uoride and hydrogen ~uoride gave the 1\1\2!tri~uorodioxane in high yield "Scheme 2# ð72JFC"11#094Ł[ The same product is also reported using the potassium salt of cobalt tetra~uoride ð60T3422Ł[ Finally\ ~uorination of 3!methylmorpholine using cobalt tri~uoride is reported to give the di~uoromethyl derivative shown in moderate yield "Scheme 2# ð67T086Ł[ O
SF4, 185 °C, 8 h; S2Cl2
O F
89%
O
O O
O
F
KCoF4, 220 °C
F 65%
O
O
F F
N
Me CoF3, 100 °C
F
N
F
31%
Scheme 3
"ii# From mixed trihalomethanes Chlorodi~uoromethane has been used extensively as a source of di~uoromethylene\ which can be intercepted by alkoxide nucleophiles to give alkoxydi~uoromethane adducts[ The conditions used
27
Halo`ens and any other Elements
are similar to those employed in the ReimerÐTiemann reaction\ and give good yields of product di~uoro ethers "Equation "3## ð47JA2991\ 59JOC1998Ł[ A phase transfer method has also been used to generate di~uorocarbene from chlorodi~uoromethane ð77JFC"30#136Ł[
R OH
i, NaOH, H2O, dioxane, 70 °C ii, CHFCl2
R
F (4)
O F
R = Ph, 65%; 4-MeC6H4, 66%; 4-MeOC6H4, 53%; 2,4-Me2C6H3, 56%; 2,4-Cl2C6H3, 44%; 2-naphthyl, 66%; Pri, 60%
The range of functionality tolerated by the reaction includes substituted primary and secondary alkyl halides\ which provides access to heavily functionalized systems "Scheme 3# ð65CB1240Ł[ Trihalomethylmercury compounds have also been used to deliver the dihalomethyl moiety to alcohols and carboxyl groups ð53JA1850\ 63JOM"56#230Ł[ Phenyl"bromodichloromethyl#mercury thus adds to carboxylic acids to yield the dichloromethyl esters shown "Scheme 4#\ and with butanol to give the dichloro ether shown in high yield\ producing phenylmercuric bromide as by!product in both cases[ Di~uorocarbene has also been generated from FSO1CF1CO1H\ and it inserts into alcohols in the presence of CuI ð78JFC"33#322Ł[ Cl
F
Cl
O
Cl
HClCF2
Cl
O
F
97%
F
OH
Cl
F
Cl
Cl
Cl HClCF2
O
O
OH Cl
Cl
F
98%
F F
F
Scheme 4
O PhHgCCl2Br + RCO2H
R
benzene, 60 °C, 45 min
Cl O
+ PhHgBr
Cl R = Ph, 86%; Me, 92%; ClCH2, 86%; But, 81%
PhEt, 80 °C, 30 min
Bu
O
PhHgCCl2Br + BuOH
Cl 85%
+ PhHgBr
Cl
Scheme 5
"iii# From dihalo ethers Treatment of dichloro ethers and bromochloro ethers with antimony tri~uoride results in halogen substitution to yield the corresponding di~uoro ether "Scheme 5# ð52AFC"2#070\ 69ZOR033\ 61JMC593\ 61JMC595Ł[ Alternatively\ anhydrous hydrogen ~uoride can be used in the presence of antimony penta~uoride giving high yields of the di~uoro adducts "Equation "4## ð61JMC593Ł[ Treatment of
28
Halo`en and a Chalco`en
cyclic per~uorinated ethers with aluminum trichloride is reported to give the corresponding a\a\a?! trichloro ether in good yield "Equation "5## ð67JFC"01#248Ł[ Cl Cl
Cl O
Cl
75%
CF3
Cl F
F
SbF3, 60 °C
Cl
F
O F
F
O
F
SbF3, 60 °C
F
70%
CF3
F
F F
O
Cl F Me
Cl
Br
O
Br
F
51%
Br
CF3 Cl
F
SbF3, 117 °C
Me
O
Br
F
F
CF3 F
Cl
SbF3, ∆
O
Br
F O
67%
Cl
C F3Cl Cl
CF3 F SbF3, ∆
Cl
Cl3C
O
Me 84%
F Cl3C
F
F O
Me
Scheme 6
Cl F Cl
F
F F
O
HF, SbCl3, 0 °C 80%
F
F
F F
O
F
F3C
F O
(5)
F
AlCl3, 143 °C, 19 min 53%
Cl F3C
F O
Cl
(6)
Cl
"iv# From carbonyl derivatives Electrochemical ~uorination of acyl chlorides and esters has been used to prepare compounds of this class[ The process gives moderate yields of cyclic per~uorinated ethers\ but often results in formation of mixtures "Scheme 6# ð67JFC"01#0\ 72JFC"12#012Ł[ Sulfur tetra~uoride has been shown to be e}ective for the conversion of the carbonyl group to a di~uoromethylene group[ Thus\ treatment of a variety of anhydrides\ esters\ and formate esters with sulfur tetra~uoride yields the corresponding di~uoromethylene systems\ often in high yield "Scheme 7# ð59JA432\ 53JOC0\ 69ZOR033\ 64ZOR0561\ 65ZOR0176\ 65ZOR0687\ 72JFC"11#196Ł[ Exposure of aryl!ortho! diacid systems to the same conditions results in ring formation in addition to partial per~uorination "Scheme 8# ð69ZOR1387Ł[ Phosphorus pentachloride has been shown to react with a variety of formate esters to yield the corresponding a\a!dichloro ethers "Equation "6## ð52CB0276\ 56OS"36#36\ 60RTC445Ł[ The analogous addition reactions are also applicable to oxalates and other carboxylic esters\ which constitute high! yielding routes to dichloro ethers\ trichloro ethers\ and dichloroacetates "Scheme 09# ð40JA4057\ 45M212\ 64S416Ł[ a!Chlorination of a!chloro!a!alkoxyacyl chlorides has also been employed\ giving the corresponding dichloroalkoxyacyl chloride in good yield "Scheme 09# ð48CB2069Ł[
39
Halo`ens and any other Elements O
C3F7 HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min
Cl 20%
F O
F3C
C4H9
HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min
OMe 21%
F O
C2F5
O OMe
CF3
HF/3.5 A/dm2, 5 °C, 6.4 V, He 100 ml/min
O
19%
F
F O
Scheme 7
Cl
Cl
Cl SF4, 300 °C, 10 h
O
O X
F
F
46%
O
O
F CF3
Cl
O
F O
SF4, HF, ∆
X
O
CF3
F
F
X = H, 61%; 4-NO2, 69%; 3-NO2, 83%; 2-Cl, 71%; 4-Cl, 74%; 4-F, 69%; 3-Me, 63%; 4-Me, 46%; 2-MeO, 36%
OCOCF3
OC2F5
OCOCF3
OC2F5
SF4, HF, ∆ 79%
OCOCF3
OC2F5
OCOCF3
OC2F5 Scheme 8
CF3
CO2H CO2H
SF4, ∆
CO2H
SF4, ∆
O
F O
76%
F
CF3 F
CO2H
CF3 F
O
CF3 F
F
Scheme 9
O R
O
Cl
PCl5, ∆
R
+ POCl3 O
(7)
Cl
R = Me, 84%; But, 68%; Ph, 85%
Another versatile route is o}ered using a\a!dichloromethyl methyl ether as a transfer agent\ in the presence of mercuric chloride[ A variety of aryl formate esters have been converted to the corresponding dichloromethyl ethers using this very high!yielding method "Equation "7## ð60RTC445Ł[
30
Halo`en and a Chalco`en O
PCl5, 80 °C
OPh
Cl
Cl
>50%
OPh
O R
O
O
Cl
PCl5, 85–90 °C, 12 h
R
R
O Et
O
Et
O
R
Cl
R = Me, 75%; Et, 85%
O
Cl
O
Cl
PCl5, 110 °C, 15 h
Et
65%
Cl
O
O
O
Et
O Cl Cl
EtO
Cl
Cl2, 150 °C
Cl Cl
EtO
70%
O
O Scheme 10
O
O MeOCHCl2, HgCl2
X
X
O
Cl Cl
(8)
X = H, 85%; 2-Me, 94%; 3-Me, 90%; 4-Me, 90%; 3-Cl, 90%; 4-NO2, 86%; 3-HCl2CO, 90%
"v# From haloalkoxyalkenes Chlorination of chloroalkoxyalkenes has been used successfully to give the corresponding dichloroalkoxyalkanes in good yield "Scheme 00#[ Typical conditions involve exposure of the alkene to a stream of chlorine gas or dry hydrogen chloride "generated in situ# at −4>C followed by distillation of the product ð46RTC858\ 47CB795Ł[ OEt Cl OEt Cl
Cl
Cl
OEt
EtO
Cl
OEt Cl Cl
dry HCl, –5 °C 73%
Cl
OEt Cl Cl
Cl Cl EtO
OEt Cl Cl
dry HCl, 0 °C 88%
dry Cl2, –5 °C 74%
Scheme 11
"vi# From haloalkenes The addition of primary alcohols to halogenated alkenes proceeds rapidly\ giving dihaloalkoxy! alkanes in high yield[ The reactions are often catalyzed by trace amounts of the corresponding metal alkoxide^ this is often required for addition of less reactive secondary and tertiary alcohols\ which usually give mixtures of products "Scheme 01# ð59JOC882\ 54AFC"3#49\ 63BSF1961Ł[ Electron! withdrawing substituents on the alkene also accelerate the reaction^ thus\ methyl tri~uoroacrylate
31
Halo`ens and any other Elements
reacts faster than methyl acrylate ð62CCC55\ 75ZOR0723Ł[ Addition of oximes has also been accomplished\ merely requiring more elevated temperatures "Scheme 01# ð62CCC55Ł[ Addition of alkyl and trihaloalkyl hypohalites to haloalkenes is another useful route to this class[ A variety of primary and tertiary alkyl hypohalites add cleanly at low temperature "Scheme 01# to give high yields of the adducts ð69JOC2629\ 64JA02\ 64JFC"4#14Ł[ Bis"tri~uoromethyl#trioxide has also been employed for this type of addition reaction\ which is applicable both to acyclic and cyclic alkenes "Scheme 01# ð63JOC0187Ł[ Per~uorinated alkenes are reported to react with sulfur trioxide to give cyclic per~uoro! 1!b!sulfones in excellent yield ð75ZOR0731Ł[ Per~uoroalkenes also react with halogen mono~uoro! sulfates to yield both 1!haloalkyl~uoroalkyl ~uorosulfates and vicinal bis"halosulfonyloxy# ~uoroalkanes ð74IZV548Ł[
F
F
F
F
Cl
F
F
BunOH, 10% Na, 0–38%
F
F
F
OBun
81%
OH
F
F
O
, 5% Na, THF, –10 °C
F
75%
F
F Cl
Br
F
Br
F
EtCO2
O
Br
79%
F N
F
F
Br
EtOH, 10% Na, –10 °C–>16 °C
F OH , DME, 10% Na, 25 °C
F
ClOMe, –80 °C
F
96%
F
F
F
O
O F
CF3 CF3 CF3 , –62 °C–>25 °C
F
CF3
F O F
CF3OO2CF3, 67 °C, 8 h
F
F
N
F
F 3C
95%
F
F O
Cl
F3C
F
EtCO2
92%
F
Et
F
F
CF3 CF3 CF3
O2CF3
F
80%
OCF3
F Scheme 12
Epoxidation of ~uoroalkenes is a convenient route to a\a!di~urorooxiranes[ High yields are attainable at low temperature using moderate to high strength hydrogen peroxide "Equation "8## ð55JOC1201\ 69JOC1943\ 61MI 591!90\ 62ZOR1902Ł[ C4F9
F
F
F
60% H2O2, MeOH, –20 °C, 8 h 82%
F
C4F9 F
F
(9)
O
a\a!Dichlorooxiranes have been used by Corey in the enantioselective synthesis of azido and amino acids "Scheme 02#[ The oxiranes\ generated in situ from trichloromethyl carbinols\ are immediately ring!opened by the SN1 attack of aqueous azide\ subsequent oxidation giving a!azido acids in high yield ð81JA0895Ł[
32
Halo`en and a Chalco`en H R
OH
H
NaOH, NaN3
CCl3
O
R
then KH2PO4
Cl Cl
N3
H
R
CO2H
R = n-C5H11, 89%; C6H5(CH2)2, 91%; c-C6H11, 89%; But, 80% Scheme 13
5[91[0[0[1 Tetracoordinated carbon atoms bearing mixed halogens and one oxygen function "R0CHal1OR1# Selective mono~uorination of dichloro ethers has been used to prepare chloro~uoro ethers in moderate to good yield "Scheme 03# ð60JMC482\ 61JMC593\ 64JFC"5#26Ł[ Another useful strategy is addition of tri~uoromethyl hypochlorite to mixed 0\0!dihaloalkenes giving the dihalo ethers in excellent yield "Scheme 03# ð69JOC2629\ 61JMC595Ł[ The ester BrCF"OPh#CO1Et has been prepared by bromination of ethyl~uoro"phenoxy#acetate ð75JOC844Ł[ Cl F Cl
F
F F
O F
F F
anhydrous HF, SbCl5 (cat.), 0 °C
F Cl
Cl
80%
F
F
F F
O F F
ClOCF3, –80 °C 90%
F3C
O F
F
Cl F
Cl
Scheme 14
5[91[0[0[2 Tetracoordinated carbon atoms bearing one halogen and two oxygen functions "R0CHal"OR#11# Numerous examples of compounds of this class exist\ as the corresponding carbenium ion halide salt\ a consequence of stabilizing in~uence of the alkoxy functions ð61CRV246\ 71S0\ 74HOU"E4#Ł[ The following examples described are clear!cut cases where the chemistry is best described by the covalent species[
"i# From 0\2!dioxolanes Direct formation of 1!~uoro!1!tri~uoromethyl!0\2!dioxolanes has been accomplished by treating aryl ortho!bis"tri~uoroacetic# esters with a mixture of sulfur tetra~uoride and hydrogen ~uoride ð65ZOR0176Ł[ Formation of 1!chloro!0\2!dioxolanes has been achieved using a variety of protocols ð56LA"696#24Ł[ Chlorination of derived ortho!esters with phosphorus pentachloride at elevated tem! peratures is a high!yielding process\ as is direct chlorination of unsubstituted 0\2!dioxolanes "Scheme 04# ð50CB433\ 55CB1514\ 56LA"696#24\ 57LA"619#035Ł[ A related procedure used substitutive chlorination of a 1!acetoxy!0\2!dioxolane using dichloromethyl ether ð58TL4992Ł[ Alternatively\ displacement of chloride from 1\1!dichloro!0\2!dioxolanes has been used ð55CB1514Ł[
"ii# From ortho!formates Decomposition of vinyl ortho!formates is a versatile route to dialkoxymethyl halides[ Treatment of dialkoxy vinyl ortho!formates with either hydrogen chloride or hydrogen bromide results in
33
Halo`ens and any other Elements Cl
O
SOCl2, 80 °C
Cl
O
92%
Cl
O
Cl
O
Cl
O
R1
O
OR2
PCl5, 110 °C
R1
O
R1
O
Cl
R2
= Ph, = Me, 88% R1 = CO2Et, R2 = Et, 53% R1 = H, R2 = Et, 87% Scheme 15
liberation of the dialkoxyhalomethane "Scheme 05# ð60RTC0012Ł[ Alternatively\ substitution of triaryl ortho!formates with acetyl chloride has been reported to give good yields of the chloro! diaryloxymethane ð51CB0748Ł[ OR
OR
HCl or HBr, Et2O, 25 °C, 15 min
O
RO
X
RO R = CH=CH2, X = Cl, 50% R = Ph, X = Cl, 60% R = Ph, X = Br, 50% R = p-Tol, X = Cl, 65% R = C(Me)=CH2, X = Cl, 90% OPh
PhO
OPh
MeCOCl
OPh
81%
Cl
PhO
Scheme 16
5[91[0[1 Halogen and Sulfur Derivatives "R0CHal1SR1 and R0CHal"SR1#1# 5[91[0[1[0 Tetracoordinated carbon atoms with two identical halogen and one sulfur function attached "R0CHal1SR1# "i# From sul_des a!Chlorination of sul_des is a popular route to these compounds\ and a variety of di}erent protocols have proved e}ective including photochemical chlorination and use of thionyl chloride "Scheme 06# ð41JA2483\ 42LA"470#022\ 47LA"505#0\ 48LA"510#7\ 54JOC3900Ł[ The ester MeSCH1CO1Me has been converted into the corresponding a\a!dichloro ester using thionyl chloride and into the dibromo ester by reaction with bromine ð70AG"E#474Ł[
Me
SOCl2, 0 °C, 1.5 h then 95 °C, 4 h
Me
S
Cl Me
Cl
Cl2, CCl4, –20 °C
Me
S
Cl
Me 57%
Scheme 17
Cl
S
77%
S
Cl
34
Halo`en and a Chalco`en "ii# From iodo~uoroalkanes
The photochemical reaction of ~uoroiodo alkanes with both methyl sul_de and dimethyl disul_de has been investigated extensively\ and the radical addition process was found to give good yields of the corresponding di~uoro sul_des "Scheme 07#\ the only drawback being the sluggishness of the reaction ð61JCS"P0#044\ 61JCS"P0#048\ 61JCS"P0#0495\ 61JCS"P0#1327Ł[ Metallation of terminal iodo~uoro! alkanes with methyllithium at −67>C\ followed by addition of sulfur dioxide\ results in formation of a lithium di~uoroalkylsul_nate by attack of the intermediate organolithium species ð78S352Ł[ F
F
F3C F I
F F
F Me
48%
I
S F
MeSSMe, UV, 30 d
F
F
F3C
93%
F
F
F
MeSSMe, UV, 21 d
I
Me
F F S
S F
Me
F
Scheme 18
"iii# From a\a!dichloroalkyl sul_des Dichloroalkyl sul_des react smoothly with antimony tri~uoride in the presence of catalytic quantities of antimony penta~uoride to yield the corresponding di~uoro sul_des "Scheme 08# ð41JA2483\ 54JOC3900Ł[ The substitutions are regioselective for the carbons alpha to the sulfur center as shown by control reactions[ F S
Me
Br
Cl
F
SbF3, SbF5 (cat.) 75%
Me
Cl
Cl
Br
F
S Cl
S
Cl Cl
SbF3, SbF5 (cat.)
Cl
46%
F
F
S F
F F
F
Scheme 19
"iv# From chlorodi~uoromethane Substitution of the chloro group of this haloform with thiols has been achieved using a variety of conditions\ typically involving addition of a sodium thiolate followed by thermolysis "Scheme 19# ð46JA4382\ 68JOC0697\ 74S386Ł[ Some debate exists concerning the mechanism of the substitution\ which appears to have both a carbene and SN1 type character[ A phase!transfer method\ which undoubtedly involves di~uorocarbene\ has been described for preparation of sul_des ArSCHF1 from aromatic thiols ð77JFC"30#136Ł[ Cl
F
PhCH2SH, NaOH 50%, DMF, 65 °C
Ph
S
F
75%
F Cl
F F
Na, MeOH then PhSH, 7 h 63%
Scheme 20
F Ph
S
F F
35
Halo`ens and any other Elements
"v# From thioformates Thioformates react cleanly with phosphorus pentachloride in carbon tetrachloride to yield the corresponding a\a!dichloromethyl sul_des in high yield "Scheme 10#[ An alternative but slightly less e.cient route to such compounds is via halomethylene transfer from dichloromethyl methyl ether\ catalyzed by mercuric chloride ð61RTC238Ł[ O R
R
+ POCl3
R
76–87%
S O
Cl
PCl5, CCl4, –40 °C–>25 °C
S Cl
MeOCCl2, HgCl2, reflux 4 h
R
75–93%
S
Cl
+ MeOCHO S
Cl
Scheme 21
"vi# From alkenes "a# Vinyl sul_des[ Chlorination of 0!chlorovinyl sul_des has been used to generate bis"alkylthio#tetrachloroethanes "Scheme 11#[ In this example the alkene is readily available via thiolate!induced substitution and elimination from the corresponding hexachloroethane ð47CB795Ł[
Cl3C
CCl3
NaSEt
EtS Cl
SEt Cl
Cl2 52%
Cl EtS Cl
Cl SEt Cl
Scheme 22
"b# 0\0!Dihaloalkenes[ Addition of thiols and disul_des to halogenated alkenes proceeds rapidly when they are subjected to either ultraviolet or x!ray radiation to give the corresponding addition products "Scheme 12#[ As expected\ addition of thiolates proceeds without photolytic conditions\ but the reaction rates are heavily dependent on the nature of the haloalkene substitutents[ Mixed chloro! and bromo~uoroalkenes are far more reactive than tetra~uoroethylene\ which requires forcing conditions ð59JA4005\ 50JA739\ 54JOC3900\ 55BCJ1080\ 61JCS"P0#23\ 63JFC"3#096\ 65JCS"P0#0067Ł[ Free! radical addition of tri~uoromethanesulfonyl chloride to haloalkenes under UV irradiation has been employed and gives moderate yields of the tri~uoromethylsul_de adducts "Scheme 12# ð51JA2037Ł[ Thermolysis of tetra~uoroethylene with elemental sulfur is reported to produce _ve!\ and six! membered cyclic sul_des bearing a\a!di~uoromethyl groups in yields ranging from 09) to 59) ð51JOC2884Ł[ Addition of thiols to di~uoroalkenes catalyzed by Triton B is also reported to produce a\a!di~uoroalkyl sul_des in high yield ð49JA2531Ł[ Activated haloalkenes\ including penta~uoro! propene!1!sulfonyl ~uoride\ undergo rapid addition of alkyl hydrosul_des\ yielding 0!alkylthio!1H! penta~uoropropane!1!sulfonyl ~uorides "Scheme 12# ð75ZOR0723Ł[
"vii# From carbon disul_de Treatment of carbon disul_de with elemental ~uorine at −019>C is reported to yield octa~uoro! ethyl methyl sul_de in 59) yield ð66IC1863Ł[
"viii# From a!~uoroalkyl sulfoxides The reaction of the sulfoxide of 3!MeOC5H3SOCH1F with "diethylamino#sulfur tri~uoride gives the di~uorosul_de 3!MeOC5H3SCHF1 "57)# by a Pummerer!type reaction ð89JOC3646Ł[ The sul_de
36
Halo`en and a Chalco`en F
Cl
F
Cl
F
RS
RSH, x-rays, 3–4 weeks, 25 °C
Cl
F
F
R = Me, 71%; Et, 61%; Pri, 74%
F
F
S
O
F
F
PhSH, dioxane, 60–80 °C
F
F
91%
F
F
F
S
Me
90%
Cl
F
F
F
F F
S Ph
F
F
ClSCF3, hν, 2 h (R = H)
F F
S F F
R
F
CF3
R = H, 50%; CF3, 63%
CF3
S
C4H9
66%
Cl
R
CF3
C4H9SH, Et2O, –60 °C
SO2F
Me
F
MeSH, 4M NaOMe
Cl
F
F3C
71%
F
F
F
CF3SH, UV irradiation 15 min
OMe F
Cl
SO2F
F
F
Scheme 23
can be oxidized to the corresponding sulfoxide and sulfone[ The reaction is\ however\ unsuccessful with PhSOCH1F[ 5[91[0[1[1 Tetracoordinated carbon atoms bearing mixed halogens and one sulfur function "R0CHal1SR1# Thiolate additions to mixed chloro~uoroalkenes under both radical and ionic conditions have been employed to synthesize mixed dihalo sul_des of this class "see Section 5[91[0[1[0#[ Typical conditions parallel those for identically substituted haloalkenes\ and product yields are comparable "Scheme 13# ð48LA"510#7\ 51JA2037\ 55BCJ1080\ 63JFC"3#096\ 65JCS"P0#0067Ł[ Alternatively\ treatment of dichloro sul_des with antimony tri~uoride results in monosubstitution of chlorine\ giving the mixed "chloro~uoro#sul_de in good yield "Scheme 13# ð48LA"510#7Ł[ The esters BrCF"SR#CO1Et "R Et and Ph# have been prepared by NBS bromination of the corresponding "ethylthio#~uoroacetate or ~uoro"phenylthio#acetate ð75JOC844Ł[ MeS–, MeSSMe
F
F
F
56%
F
Cl
ClSMe, hν, 26 h
Cl
42%
S
Me
F S
S
Cl Cl
SbF3 72%
Scheme 24
F 3C
F F F
Me
F3C
S Me
Cl
F
S
Cl
Cl F
37
Halo`ens and any other Elements
5[91[0[1[2 Tetracoordinated carbon atoms bearing one halogen and two sulfur functions "R0CHal"SR1#1# As in the case of many compounds described in Section 5[91[0[0[2\ much of the chemistry of compounds of this class is represented by the corresponding halothiolium salts ð55AHC"6#28\ 79AHC"16#040Ł[ Cases illustrated below are con_ned to systems where the chemistry is best represented by the covalently bound species[ "i# From thioacetals Chlorination of 0\2!dithianes has been used to generate versatile 1!chloro!0\2!dithianes which are useful for coupling reactions of this masked carbonyl[ Typical conditions involve either sulfuryl chloride or N!chlorosuccinimide\ and recovered yields are high "Scheme 14# ð65BCJ442\ 66TL774\ 68JOC0736Ł[ SO2Cl2, CHCl3
S
S
95%
S
S Cl
S
S NCS, PhH, 20 °C, 30 min
S
S
95%
S
S Cl
Scheme 25
"ii# From thioformates and ortho!thioesters Ortho!thioesters can be monochlorinated successfully using either phosphorus chlorides or acetyl chloride as donors\ giving moderate yields at elevated temperatures "Scheme 15# ð50LA"537#10\ 66JPR06Ł[ An alternative procedure involves treatment of thioesters with a dichloromethyl aryl ether in the presence of mercuric chloride "Scheme 15#[ This procedure\ however\ is less e.cient in that it requires 1 equivalents of thioester ð61RTC238Ł[ SMe SMe
MeS
SMe
MeCOCl, 70 °C 63%
SMe
Cl
O
SEt SEt
EtS
O
PCl3 O CCl4, 78 °C, 1 h 70%
SEt SEt
Cl
SPh
0.5 PhOCHCl2, HgCl2, 90 °C
SPh
80%
SPh
Cl CF3
S
UV irradiation, 3 h, Cl2CF2
Cl
F 3C
Cl
S Cl
S
93%
CF3 CF2Cl S ClF2C
UV irradiation, 3 h, Cl2CF2
F
83%
F
S S
F CF2Cl
Scheme 26
Halo`en and a Chalco`en
38
"iii# Dimerization of thiocarbonyl compounds A variety of substituted thiocarbonyl compounds are reported to undergo rapid dimerization on irradiation with UV light ð54JOC0264Ł[ The corresponding 0\2!dithietanes are formed in high yields\ and are easily puri_ed by distillation "Scheme 15#[
5[91[0[2 Halogen and Se or Te Derivatives "R0CHal1SeR1 or R0CHal1TeR1# 5[91[0[2[0 Tetracoordinated carbon atoms bearing two halogens and one selenium function "R0CHal1SeR1# A variety of examples of compounds from this class have been reported\ and their preparation often involves transmetallation reactions of metal selenyl dihalomethyl derivatives[ Bis"penta~uoroethyl# monoselenide has been prepared by reaction of selenium powder with the corresponding penta~uoroethyl silver salt ð52JCS0157\ 62JCS"D#1203Ł[ Thermolysis of selenium metal with tetra~uoroethylene in the presence of catalytic amounts of iodine\ however\ results in the formation of a mixture of octa~uoroselenolane and octa~uoro!0\3!diselenane "Scheme 16# ð51JOC2473Ł[ Tetra~uoroethylene also reacts with tetraselenium bis"hexa~uoroarsenate"V## over extended periods of time to yield bis"per~uoroethyl# diselenide in good yield "Scheme 16# ð66CJC2025Ł[ Similar reactions have been perfomed using Se7"AsF5#1\ and Se7"Sb1F00#1\ which both react with tetra~uoroethylene to give the bis"per~uoroethyl# diselenide in nearly quantitative yield ð62JCS"D#1203Ł[ Reaction of selenium metal with tri~uoroiodomethane results in the formation of bis"tri~uoromethyl# mono! and diselenide ð47JCS1828Ł[ Similarly\ reaction of silver hepta~uoro! butyrate with selenium metal results in the formation of hepta~uoropropyl mono! and diselenide ð48ZOB831Ł[ Reaction of this diselenide with mercury results in the formation of bis"hepta~uoro! propylseleno#mercury\ which is a versatile alkylseleno transfer agent "Scheme 16# ð52JCS0157Ł[ Treatment of this\ and related mercurials\ with iodine results in near quantitative conversion back to the bis"hepta~uoropropyl# diselenide ð54JCS6400Ł\ whereas combination with 1 equivalents of iodosilane results in good conversion to the corresponding silyl selenide "Scheme 16# ð51JCS1189Ł[ Diselenides also react with manganese pentacarbonyl hydride to yield the corresponding organo! selenium manganese complexes ð54JCS6404Ł[ It has been reported that chlorination of 1\4!dibromo! selenophene results in the formation of 1\4!dibromoselenophene!1\2\3\4!tetrachloride\ although no details of conditions or yield were provided ð25BCJ046Ł[ Diphenyl diselenide reacts under dissolving metal reduction conditions to form an intermediate sodium selenide[ This species can be intercepted with per~uoroalkyl iodides under photolytic conditions to yield per~uoroalkyl selenides in moderate yield "Scheme 16# ð66ZOR1997Ł[ Bis"per~uoroethyl# monoselenide reacts with iodine monochloride to form di~uoro"per~uoroethyl#selenium in quantitative yield ð65JFC"6#150Ł[ Selenocarbonyl di~u! oride is reported to undergo addition with amines to yield an unstable amino di~uoromethyl adduct ð89JOM"275#210Ł[ Tri~uoromethyl selenocarbonyl ~uoride "Se1C"F#CF2#\ produced by thermal 0\1 elimination of trimethyltin ~uoride from trimethylstannylpenta~uoroethylselenane\ is also reported to undergo similar addition reactions ð89JOM"275#210Ł[ Di~uoromethyl selenoethers ArSeCHF1 can be prepared from chlorodi~uoromethane and ArSe− ð74S386Ł[
5[91[0[2[1 Tetracoordinated carbon atoms bearing two halogen and one tellurium function "R0CHal1TeR1# Di~uoromethyl compounds of tellurium were unknown until the mid!0889s[ A general protocol has been reported in which dimethyl telluride is reacted with either a bis"tri~uoromethyl# cadmium or tri~uoromethylzinc bromide in the presence of acetonitrile and boron tri~uoride "Scheme 17# ð83AG"E#212Ł[ The route is reported to be general for all chalcogens\ thus in a similar manner\ methyl "di~uoromethyl# selenide is also formed^ however\ isolated yields were not reported in either case[ Per~uoroalkyl tellurides\ however\ have been prepared by a variety of means ð64JCS"D#377Ł[ One method involves reaction of per~uoroalkyl radicals on a tellurium mirror\ giving low yields of per~uoroalkyl ditelluride ð52AJC611Ł[ A more e.cient method for the preparation of bis~uoroethyl monotelluride is to react tetra~uoroethylene with Te3"AsF5#1 in a Monel reactor "Scheme 17#[ This method is general\ and manipulation of conditions allows formation of varying amounts of the
49
Halo`ens and any other Elements F
F
F
Se
Se, I2, 250 °C, 7 h
F Se
F
+
F Se 5%
10%
F
F
F
F
F
F
OAg
2 SiH3I, 25 °C
H
71%
Ph
Se
Se
Ph
H
H Si
Se
CF3
F
F F
F Se
F3C
ii, Hg, 48 h 99%
Hg(SeC3F7)2
Se
F
i, Se, 280 °C, 2 h
F
F
F3C
87%
O
F3C F
F
Se4(AsF6)2, 14 d, 25 °C
Hg
F
F
F
F
F
Se
C2F5
i, Na, NH3(liq.) ii, C3F7I, hν
Ph 50%
F
Se
CF3 F
+ HgI2
Se
CF3
F
F
Scheme 27
corresponding ditellurides ð64JCS"D#377Ł[ Per~uoroalkyl tellurides have also been prepared from lithium aryl tellurides "obtained by reduction of diaryl ditellurides with LiAlH3# under photo! chemical conditions "Scheme 17# ð68ZOR0450Ł[ Cd(CF3)2, MeCN, BF3, –30 °C
Me2Te
Me
F
Te F
F F
F F
Te4(AsF6)2, 100 °C, 15 atm 87%
F F3C
F
F
F CF3
Te
C3F7I, hν, 30 min
TeLi
Te 44%
C2F5 F
F
Scheme 28
5[91[0[3 Halogen and Mixed Chalcogen Derivatives "R0CHal"OR1#"SR2## Chemistry of these systems is chie~y described by the corresponding oxathiolium salts\ thus excluding their detailed coverage in this section[ The reader is encouraged to consult references describing such systems ð63JHC832Ł[
5[91[1 FUNCTIONS CONTAINING HALOGEN AND A GROUP 04 ELEMENT AND POSSIBLY A CHALCOGEN 5[91[1[0 Halogen and Nitrogen Derivatives] General Considerations Compounds of this general class are somewhat unstable\ with the major contributing isomeric forms being the corresponding haloiminium salts\ for example\ RCHal1NR0R1\ which behaves as
Halo`en and a Group 04 Element
40
RC1N¦R0R1 Hal− ð59AG725Ł[ The degree to which such quaternary salts are formed depends on the overall basicity of the amino "and chalcogen# groups^ thus\ for most compounds of the classes RCHal1NR0R1\ RCHalNR0R1OR2 and RCHalNR0R1SR2 both species must usually be considered whereas\ for compounds of class RCHal"NR0R1#1\ the overriding chemistry is that of the halide salt\ the only exceptions being in cases where "NR0R1#1 1 "NO1#1\ where the electron!withdrawing capacity of the nitro groups diminishes the tendency to ionize[ Several review works discuss this dynamic equilibrium and should be consulted further ðB!65MI 591!90\ B!68MI 591!90\ B!68MI 591!91\ B!68MI 591!92\ B!68MI 591!93\ B!68MI 591!94\ 74HOU"E4#Ł[
5[91[1[0[0 Tetracoordinate carbon atoms bearing two halogens and one nitrogen function Numerous examples exist of compounds in this category[ In many cases\ however\ the chemistry of the product is often described by the corresponding haloiminium salt ð68S130Ł[ All examples described here re~ect cases where product equilibria lie in favour of the covalent species[
"i# From imines Addition of halocarbenes to imines has been successfully used to form 1\1!dihaloaziridines bearing a variety of substituents "Scheme 18# ð48CI"L#0105\ 51JOC2575\ 60JOC2516\ 62ZOR1235\ 63JOC047\ 65JOC2683\ 66ZOR0746\ 67JOC0235\ 68H"01#526Ł[ Methods for formation of the requisite dihalocarbene vary as does the e.ciency of the addition reaction "Scheme 18#[ Addition of ClF to imines takes place at room temperature\ to give N!chloro~uoroalkanes in high yield "Scheme 18# ð64IC0112Ł[ Cl Ph
CHCl3, KOBut, 25 °C, 18 h
N
X
N X = H, 80%; Cl, 68%; OEt, 91%
Ph N
Ph
Cl N
X
Ph Br
HCBr2Cl, KOBut, hexane, 25 °C, 3 h 61%
Ph
Cl
Cl
Cl N
Ph Cl
Ph
Cl
PhHgCCl2F, benzene, 80 °C, 40 h 74%
Cl
N Cl
Ph
Scheme 29
"ii# From amines A variety of halogenation procedures have been applied to tertiary amines\ yielding the cor! responding dihaloaminoalkanes with good conversion[ Yields obtained for di~uoroaminoalkanes using electrochemical ~uorination methods are usually modest\ halogen substitution using sulfur tetra~uoride being a far superior method "Equation "09##[ Perchlorination is also an e}ective route\ giving high yields of a\a!dichloroalkylamines "Scheme 29# ð48CCC3937\ 58LA"629#039\ 66JFC"8#168\ 79JFC"06#54\ 70AG"E#536\ 70ZAAC"363#6Ł[
41
Halo`ens and any other Elements F3C F
CF3 F
F
F3C
98%
F
N
(10)
CF3
Cl
F
Me
N
F
electrochemical
Me
Cl
F
F
ClF, 6 h, 25 °C
N
F
F3C
fluorination 51%
CF3
N
CF3
Cl
F
F
SF4
Cl
N
Cl
F
quantitative
N
Me
F
Me Cl
Cl
N
Cl2
Me
Cl 80%
Me
N Cl
Cl Cl
CCl3 Cl
Scheme 30
"iii# From amides and thioamides Treatment of formamides with chlorinating agents such as thionyl chloride and phosgene often results in formation of dichloroaminoalkanes which exist in equilibrium with the derived chloro! iminium salts "Scheme 20# ð48HCA0542\ 53CB0250\ 68MI 591!91Ł[
+
H
R
R
N
N
Cl– +
COCl2
CHO
H
R
R
N
N
Cl– Cl
H
R = Me, 80%; Ph, 92%
Me
Cl–
Me SOCl2
N
+
Me O
Cl Cl
Me
N 98%
Cl
R N Cl
Cl
Me
R N
Me
Cl
N Cl
Scheme 31
Many such systems of this class have been prepared where electron!withdrawing groups limit the possibility of salt formation[ A wide range of halogenation protocols have been successfully used in these instances\ with a generally high level of conversion to product[ These methods are useful not only for amides but also for thioamides "Scheme 21# ð59JA432\ 51JA3164\ 63JA814\ 64IC0112\ 65ZOR1102\ 67CB810\ 67JOC0616\ 68AG"E#504\ 70JFC"07#82\ 71PJC0258Ł[ Treatment of DMF with carbonyl di~uoride is also reported to give a good "71)# yield of di~uoro"dimethylamino#methane ð51JA3164Ł[
"iv# From acyl halides Treatment of acyl ~uorides with tetra~uorohydrazine under photolytic conditions results in formation of the corresponding N\N!di~uoroaminoalkane "Equation "00##[ One drawback of this radical addition protocol is the requirement that quartz reaction vessels be used ð57JOC2564Ł[
Halo`en and a Group 04 Element CF3
O
Cl CF3
Cl
PCl5, 25 °C, 6 h
CF3
N
F3C
42
O
F N
F15C7
CF3
N
F3C
99%
F
SF4, HF, 150 °C, 18 h
CF3
N
F15C7
78%
CF3
CF3
CF3 O
F N
FCOF, 25 °C, 20 h
Me
F
82%
Me
N
Me
Me
Me N
Me
SF4, KF, 150 °C, 144 h
N Me
90%
F
O O F3C
N
Cl2, CCl4, 20 °C
Et
70%
Cl
Cl
F3C
N
Me
F
Et
Et
Et Scheme 32
O C3F7
N2F4, 40 h, 20 °C, hν
(11)
C3F7NF2
90%
F
"v# From nitriles Chloro~uorination of nitriles is a mild and convenient method for preparation of N\N!dihalo! aminoalkanes[ The reactions have only been reported for nitriles bearing electron!withdrawing groups\ but yields are good to excellent "Scheme 22#[ The intermediate haloimine can be exposed to elemental ~uorine to give N!~uorochloroamines or it can be reacted sequentially with ClF to yield N\N!dichloroamines ð55IC377\ 68JA6539\ 70IC0Ł[ Addition of hydrogen ~uoride to a mixture of HCN and carbonyl ~uoride\ catalyzed by caesium ~uoride\ is reported to yield di~uoromethylcarbamoyl ~uoride\ CHF1NHCOF "69)# ð51JA3164Ł[ Treatment of per~uorinated cycloalkyl nitriles with silver ~uoride at elevated temperature is reported to yield the corresponding per~uorinated cyclo! alkylmethylazo compounds ð73JCS"P0#344Ł[ F
F
R
N
ClF, 0 °C
R
N
ClF, –195 °C
R
Cl
Cl NCl
F F2, –25 °C, 1 h R = CF3, 75%; ClF2C, 70%
F
F
R
N
F
Cl Scheme 33
"vi# From haloiminium salts Treatment of haloiminium salts with hydrogen halides provides a facile route to a!dihaloamines "Equation "01##[ The reactions are typically conducted at or below 9>C in chlorinated solvents\ and
43
Halo`ens and any other Elements
yields of addition products\ which are in equilibrium with their corresponding hydrohalide salts\ are good to excellent ð50CCC2948\ 51CCC1775\ 52CCC1936Ł[ X
+
Me
N
(12)
N
X = Br, 98%; I, 82%; Cl, 77%
Me
Me
X
HX, CHCl3, 0 °C
X–
Me
X
"vii# From haloalkenes and haloalkanes Addition of diethylamine to chlorotri~uoroethene results in the formation of the corresponding diethylaminoalkane in moderate yield "Equation "02## ð70AG"E#536Ł[ The product\ 1!chloro!0\0\1! tri~uorotriethylamine "CTT#\ is a ~uorinating agent ð48JGU1014Ł[ A similar addition reaction has been applied to related secondary amines ð70JFC"07#82Ł[ N!Iodobis"ditri~uoromethyl#amine is reported to add to hexa~uoropropene under photochemical conditions to give "F2C#1NCF1CFICF2 in low yield ð60JCS"C#2722Ł[ ð2¦1Ł Cycloaddition of benzyl azide to hexa~uoropropene gives an intermediate triazoline in 74) yield\ which undergoes thermal decomposition at 149>C to give the corresponding 0!benzyl!1\2\2!tri~uoro!1!"tri~uoromethyl#aziridine "63)# ð55JOC678Ł[ Cyclo! addition of per~uorobutadiene to tri~uoronitrosomethane is reported to give per~uoro!1!methyl! 2\5!dihydro!0\1!oxazine in 59) yield ð54JCS5038\ 55ZOB617\ 56JCS"C#1152Ł[ The azido ester BrCF"N2#CO1Et has been prepared "36)# by reaction of ethyl dibromo~uoroacetate with sodium azide ð75JOC844Ł[ F Cl
F
F
Et2NH 61%
F
Et N
Cl F
(13)
Et
F
CTT
"viii# Routes speci_c to dihalonitroalkanes "a# From nitromethanes[ Di~uoronitromethane reacts with formaldehyde under basic conditions to give 0\0!di~uoro!0!nitroethanol in 77) yield "Scheme 23# ð56ZOB041Ł[ Reactivity of its stabilized anion extends to Michael!type processes\ but only moderate yields of addition products are obtained even for addition to such activated systems as acrylonitrile and ethyl acrylate ð68IZV0800Ł[ Dibromo! nitromethane is reportedly formed when nitromethane is exposed to t!butyl hypobromite ð65JOC0174Ł\ and 0\0!dibromoethane has been prepared from nitroethane by sequential reaction with butyllithium and bromine ð78ZOR1389Ł[ F F
HCHO, K2CO3, H2O
NO2
F
88%
X , NaOEt, K2CO3
F NO2
X = CO2Et, 27%; CN, 13%
F
HO F
NO2
F
X F
NO2
Scheme 34
"b# From haloalkenes[ Fluoroalkenes are reported to react with sodium nitrite in polar aprotic solvents to furnish ~uoronitroalkanes in moderate yield "Scheme 24# ð63IZV1033Ł[ Similar addition reactions can be accomplished using perhaloalkenes and a mixture of concentrated nitric and hydro~uoric acids ð52IZV0835Ł[ 0\1!Dichloro!0\1!di~uoroethylene is converted by nitration followed
Halo`en and a Group 04 Element
44
by reaction with fuming nitric acid into chloro~uoronitrosomethane\ which can then be oxidized to chloro~uoronitromethane ð89MI 591!90Ł[ F
F
F
F3CO
F
F
F
Cl
NaNO2, DMF, 3 d
F
F3CO
50%
F
HNO3 (100%), HF, 20 °C, 7 h
F
F
F
F
Cl
88%
NO2
NO2
F Scheme 35
"c# From nitro alcohols[ 1!Fluoro!1!nitro!0!butanol reacts with aqueous sodium hypobromite to give 0!bromo!0!~uoro!0!nitropropane "Equation "03##[ The reaction is believed to proceed via a transient a!~uoronitronate salt ð69JOC735Ł[ F
NO2 OH
Et
NaOBr, NaOH (aq.), 10 °C, 40 min
F
57%
NO2
Et
(14)
Br
5[91[1[0[1 Tetracoordinate carbon atoms bearing one halogen and two nitrogen functions In all cases in which the nitrogen functions are amino groups\ attempts to prepare compounds of this class results in the formation of the corresponding haloiminium salts[ Examples are widespread\ covering simple amines ð54CB0967\ 62LA39\ 64LA084Ł\ cyclic amines ð50CB1483\ 58RTC178Ł and hydra! zines ð60JOC0044Ł[ One class of compounds within this category which retains stability\ however\ are the halo! diazirines "Scheme 25#[ Typical conditions involve exposure of an acetamidine to bromide saturated DMSO with sodium chlorite] the so!called {Graham conditions| ð54JA3285\ 56JA071\ 57JOC0736\ 70JA5053\ 76TL4790\ 78ACR04Ł or treating N\N!dihaloamidines with base "Scheme 25# ð70JOC4937Ł[ N R
N F3C
H NH2
Cl TRIGLYME, DMSO, 10% NaOH, NaCl, 0 °C
NHCl
NaOCl, NaBr DMSO, LiBr 30%
R = Pri, 49%; MeO, 43%
N N F3C
Br
N N R
tbaf, MeCN 50%
Cl
N N F 3C
F
Scheme 36
"i# Tetracoordinate carbon atoms bearin` one halo`en and two nitro `roups "RCHal"NO1#1# Nearly all compounds in this class have been prepared from the salts of dinitroalkane anions\ reacting with a halogenating agent[ They are grouped according to the nature of the halogenation procedure employed[ "a# Usin` elemental halo`ens[ Typically\ conditions involve formation of the potassium salt of the dinitroalkane\ followed by exposure to the halogen source in situ[ The salts are either prepared by treating the dinitroalkane with the required potassium base or\ in the case of dinitromethane\ via a Ter Meer reaction with chloronitromethane\ itself available by chlorination of nitromethane[ The most commonly used procedure is to pass a ~uorineÐnitrogen mixture into the aqueous solution of the salt at or close to 9>C "Scheme 26# ð57IZV320\ 57IZV1296\ 58IZV0220\ 62IZV0313\ 67JOC2374Ł^ xenon di~uoride is also e}ective as a ~uorinating agent ð76ZOR0546Ł[ Similarly high yields have also
45
Halo`ens and any other Elements
been obtained using the sodium or ammonium salts of dinitroalkanes ð57IZV801Ł and of 1\1! dinitropropane!0\2!diol in which one of the hydroxymethyl groups is cleaved "Scheme 26# ð57JOC2979Ł[ Chlorination of the sodium salts are also reported to give excellent yields of the derived chlorodinitroalkane "Scheme 26# ð58IZV1506\ 76IZV295Ł\ and bromodinitromethane has been prepared by reaction of the sodium salt of dinitromethane with bromine[ ICl has been used to form the corresponding iododinitroalkanes ð66IZV1947Ł[ NO2
NO2
F2, H2O, 0–5 °C
K+
–
NO2
R
F
NO2
R
R = H, 65%; CH2CH2CN, 60%; CH2C(NO2)2, 81%; p-C6H4NO2, 62%; m-diC6H3NO2, 92% NO2 NO2
O2N
76%
NO2
NO2
NO2
NO2
HO
F NO2
84%
Na+
–
NO2
NaOH, H2O, F2, 2.5 h, 0–5 °C
NO2 NO2
F
82%
OH
+ NH4F
NO2
NaOH, H2O, F2, 2 h, 0–5 °C
NO2
HO O2N
F O2N
90%
I
NO2
R
F2, N2, H2O, 1 h, 2–3 °C
NH4+
–
NO2
ICl, CCl4, 10–15 °C
K+
–
NO2
NO2
Cl2, 0–5 °C 99%
Cl
NO2
Scheme 37
"b# Usin` perchloryl ~uoride[ Most work in this category has been conducted using potassium salts of the dinitroalkanes\ providing a generally high yielding approach to the desired ~uoro! dinitroalkanes "Equation "04## ð57JOC2962\ 69IZV276\ 60IZV0376Ł^ similar results "albeit with inferior yields# are obtained using sodium salts ð61JOC041Ł[ For systems where the corresponding salts of dinitroalkanes are unstable\ use of hexamethylphosphoramide "HMPA# and perchloryl ~uoride is reported to allow e.cient ~uorination within 1 hours "Scheme 27# ð58IZV0077Ł[ Interestingly\ exposure of ClOSO1F to cyano!substituted dinitroalkane salts results in formation of the derived N!chloroimidates "Scheme 27# ð65IZV378Ł[ NO2 –
K+
NO2
FClO3, MeOH, 25 °C
F
NO2
R
R
(15)
NO2
R = Ph, 95%; CH2CH2CO2Me, 88%; CH2NHCOPh, 88%; CH2CH2NHCOMe, 93%; CH2CH=CH2, 69%
"c# Usin` hydro`en halides[ Treatment of sulfonium dinitroylides with hydrogen halides results in rapid formation of the corresponding halodinitroalkane "Equation "05##[ The cleavage method is applicable to a range of electrophilic halogen sources including elemental halogens and hypohalites\ with a dialkyl sul_de being the chief by!product ð66IZV028Ł[ NO2 Me
+
S Me
NO2
excess HX, MeCN
+ Me2S
–
NO2
X = Br, 76%; Cl, 89%
X
NO2
(16)
Halo`en and a Group 04 Element NO2
NO2
O2N
FClO3, HMPA, 2 h, 20 °C 88%
NO2
NO2 –
NC
Na+
ClOSO2F, 16 h, 20 °C
NO2 NO2 F
NO2
F O2N
NO2
Cl
N
O2N
66%
NO2
46
Cl
OSO2F Scheme 38
"d# Functional `roup interconversion of dinitrohaloalkanes[ The ~uorodinitromethanide anion undergoes a variety of additional transformations relevant for this section[ Most importantly\ under basic conditions\ 0\ 1 additions to aldehydes are possible to yield secondary alcohols ð69JOC2077Ł\ as are 0\ 3 additions to conjugated alkenes ð68S200Ł\ giving high yields of addition products in both cases[ Related examples of compounds incorporating this functionality where the dinitrohalo group is left intact include acid!catalyzed dimerization of dinitro~uoroalcohols ð58JOC34Ł\ hydrolysis of ~uorodinitroacetonitrile to yield ~uorodinitroacetamide ð57JOC0146Ł and dehydroxymethylation of 1\1!dinitro!1!~uoroethanol ð58JOC34Ł[
"ii# Tetracoordinate carbon atoms bearin` one halo`en\ one nitro `roup and one other nitro`en function An example of this class is the ester BrC"N2#"NO1#CO1Et\ which was obtained in low yield from ethyl dibromonitroacetate by reaction with sodium azide ð75JOC844Ł[
5[91[1[0[2 Tetracoordinate carbon atoms bearing one halogen\ one nitrogen and one oxygen function Based on the previous discussions concerning the stability of ortho!ester halides attached to basic functionality\ salt formation is predominant[ Probably the best studied example of this class is the Vilsmeier reagent and related systems\ formed when formamides are exposed to chlorinating agents "Scheme 28# ð47CCC341\ 48HCA0548Ł[ The equilibrium lies heavily in favour of salt formation\ explain! ing in this case\ and related examples ð58TL1050\ 60CPB1518Ł\ why members of this class have received scant attention[ Other examples can be found describing intermediate formation of this class of compound\ which quickly undergoes rearrangement to give the halide salt ð57JOC0973\ 69CPB673\ 61TL3106\ 62TL3400\ B!68MI 591!92\ 79IZV1245Ł\ and in some cases to give enamines ð54JOC3292\ 57T3106Ł[ R +
R R
R
R POCl3, CH2Cl2
N
R O
N
N
Cl [PO2Cl2]–
Cl OPOCl2
R +
R
N
OPOCl2
Cl–
Scheme 39
5[91[1[0[3 Tetracoordinate carbon atoms bearing one halogen\ one nitrogen and one sulfur function Compounds of this class in which the nitrogen function is an amino group are nearly always found in the form of the corresponding iminium halide salt ðB!68MI 591!94Ł[ The exceptions are nitrohalosul_des[ 0!Chloro!0!chlorosulfenylnitroalkanes have been reported ð74HOU"E4#Ł and the esters PhS"NO1#CXCO1Et "X Br\ and F# have been prepared by halogenation of the ester PhS! "NO1#CHCO1Et ð75JOC844Ł[
47
Halo`ens and any other Elements
5[91[1[1 Halogen and Phosphorus Derivatives 5[91[1[1[0 Tetracoordinate carbon atoms bearing two halogen and one phosphorus function and one halogen and two phosphorus functions "i# From haloalkenes Addition of phosphine to ~uoro and chloro~uoroalkenes is a general route to compounds of this class[ Generally\ the addition reactions are conducted at elevated temperatures\ often in sealed tubes[ Phenylphosphine has also been employed\ with only slight loss of e.ciency resulting "Scheme 39# ð48JA3790\ 54AFC"3#49Ł[ If the reactions are conducted under photolytic conditions\ however\ yields are often substantially improved\ with 73) for the addition to tetra~uoroethylene reported ð52JCS0972Ł[ F
F
X
F F
F
F F
PH3, 150 °C, 8 h
F F
X = F, 53%; Cl, 54%
PPhH2, 150 °C, 8 h 45%
F P
X
H
F
F
F
P F
H
Ph
H
Scheme 40
"ii# From haloalkanes Thermolysis of carbon tetra~uoride with red phosphorus in the presence of iodine results in the formation of a cyclic bis"phosphine# in moderate yield "Scheme 30# ð51JOC2473Ł[ 1\1\1!Trichloro! acetic amidines and imidates react with trialkyl phosphites to yield 1\1!dichloro!1!"dialkoxyphos! phinyl#acetamidines and acetimidates\ respectively "Scheme 30# in good to high levels of conversion ð68ZOB0914Ł[ If the reactions are prolonged\ a second substitution occurs giving a monohalobis"dialkylphosphinyl# derivative[ Addition of chlorodi~uoromethane to sodium diethylphosphonate results in the formation of diethyl di~uoromethylphosphonate ð48JGU0004Ł[ The mechanism of this reaction appears to involve capture of di~uorocarbene rather than an SN1 type process[ Prompted by research on purine nucleoside phosphorylase inhibitors\ it has been shown that diethylphosphinyldi~uoromethyllithium condenses with ortho!a!bromoxylene to give the corresponding di~uorophosphonate in 32) yield "Scheme 30# ð81BMC396Ł[ Interestingly\ other metal dialkylphosphinyldi~uoroalkane derivatives proved vastly inferior in this reaction[ Diisopropylphosphinyldi~uoromethyllithium was shown to give good yields of the 0\1!addition product to o!tolualdehyde at low temperature "Scheme 30#^ the benzylic alcohol was subsequently converted into the tri~uoro derivative using diethylaminosulfur tri~uoride ð81BMC396Ł[ Diethyl "lithiodi~uoromethyl#phosphonate has also been used to introduce the a\a!di~uorophosphonate moiety into phosphate isosteres ð81TL0728\ 83TL2116Ł[ Though alkyl halides are often poor substrates in such coupling reactions\ Martin has reported conditions for addition to aldehydes\ where the resulting product carbinols are deoxygenated using a Barton!type protocol ð81TL0728Ł[ The process is versatile\ tolerant of latent functionality\ and complements existing methods for the introduction of this important moiety ð70JFC"07#086\ 71TL1212\ 78JOC502\ 78TL6902\ 80TL0908Ł[ Dialkyl "iodo~uoro! methyl#phosphonates\ available from dialkyl "bromodi~uoromethyl#phosphonates\ are reported to undergo reductive dimerization to yield tetra~uoroethyl derivatives using cadmium powder\ re~ux! ing in methylene chloride "Scheme 30# ð83JOC1282Ł[ The corresponding dialkyl "bromo! di~uoromethyl#phosphonates fail to undergo this coupling using cadmium\ but this was _nally e}ected using a nickel derivative[ The nickel approach also facilitated dimerization of a dialkyl "iodotetra~uoroethyl#phosphonate\ giving the coupled product in 37) yield ð83JOC1282Ł[ The addition of diethyl trichloromethylphosphonate to alkenes\ catalyzed by copper chloride\ has been reported ð83TL2426Ł[ Ethyl acrylate thus gives the corresponding dichlorophosphonate in moderate yield "Scheme 30#[
Halo`en and a Group 04 Element
48
I F CF4
P(red), I2, 220 °C, 8 h
F
28%
F
F
P
F F
P
F
F
I NH Cl
NH2
Cl
P
RO
R = Et, 84%; Prn, 62%
NH (RO)3P, CH2Cl2, 50 °C, 1.5 h
RO
R = Et, 70%; Prn, 85%
RO
OMe
Cl
Cl NH
Cl
F
P Cl
O
NH
P
OEt P OEt O
F Li
F P O
CHO
F
O
OPri OPri
F
MeO MeO
EtO EtO
O
P
P
Br
F
F
F
F
Zn, NiCl2(PPh3)2 Et4NI, MeCN, 45 °C
EtO EtO
Cl Cl
P Cl
59%
Scheme 41
F
O
OPri OPri
F P
F
O
OEt OEt
F
P
P
OMe OMe
F
F
O
O
F
F F
F
P
P F
OEt OEt , CuCl
F
O
P
48% O
O
MeO
47 %
Zn, NiCl2(PPh3)2 Et4NI, MeCN, 45 °C
O
F
MeO
F
EtO
EtO EtO
Br
F
OH
69%
F
O
P
Cd, CH2Cl2
I
OEt OEt
F
, THF, –78 °C
O
F
F P
80%
EtO
NH2 Cl
43%
Br
P
OMe
Cl
F
Li
EtO
NH
EtO EtO P EtO O
62%
Cl
Cl
O
EtO
(EtO)3P, CH2Cl2, 85%, 2 h
NH2
Cl
NH2
Cl
Cl
Cl
NH
O
RO
(RO)3P, CH2Cl2, 50 °C, 1.5 h
F F
O
F O P
EtO Cl Cl
Cl
O
OEt OEt
OEt OEt
59
Halo`ens and any other Elements
5[91[1[2 Halogen and Arsenic Derivatives 5[91[1[2[0 Tetracoordinate carbon atoms bearing two halogens and one arsenic function Dimethylarsine is reported to add to hexa~uoropropene to give the corresponding dimethylarsenic derivative "Scheme 31# ð54AFC"3#49Ł[ Unfortunately\ no details either of yield or of conditions for this process were reported[ Another report describes the reaction of tetramethyldiarsine "{cacodyl|# with hexa~uoropropene to produce a ~uorodiarsine in 07) yield "Scheme 31# ð53CJC0012Ł[ Me Me
F
F
F
Me2AsH
As
CF3
F
F
F
Me F
Me2AsAsMe2
CF3
As
Me
18%
F3C
F As
Me
F Me
Scheme 42
5[91[2 FUNCTIONS CONTAINING HALOGEN AND A METALLOID AND POSSIBLY A CHALCOGEN AND:OR GROUP 04 ELEMENT 5[91[2[0 Halogen and Silicon Derivatives A variety of a\a!dihaloalkylsilanes are known but few general methods for their preparation exist ð53CB0562Ł[ The following examples cover speci_c cases where conditions have been examined and optimized[
"i# Dichlorocarbene additions Addition of dichlorocarbene "generated from phenyl"bromodichloromethyl#mercury# to a variety of silanes has been reported\ giving good yields of a dichloromethyl silanes "Scheme 32#[ Competition experiments have been carried out in order to determine the kinetics and the precise mechanism of this electrophilic addition process ð56JA0427\ 57JA1833\ 82T7376Ł[ Me Si Me
Cl
PhHgCCl2Br, PhH, 80 °C
Si
58%
Me
Me
Cl Me
Me
Si H
Si
PhHgCCl2Br, PhH, 80 °C
Cl
68%
Me Si R
Me
H Me
Cl
R 34–67%
Me Cl
Si
PhHgCCl2Br, PhH, 80 °C
Cl
Scheme 43
"ii# Other additions to silanes Low temperature metal halogen exchange of bis"trimethylsilyl#dichloromethane followed by protonation has been used to prepare bis"trimethylsilyl#chloromethane "Scheme 33# ð60JOM"18#278\ 89T2748Ł[ Bromination of alkynylsilanes has also been reported\ the major isolated addition product being the tetrabromosilane in nearly quantitative yield "Scheme 33# ð56IZV582Ł[ An alternative
50
Halo`en and a Metalloid
approach to dihalosilanes is cleavage of a bis"trichloromethylsilyl#dichloromethane using hydro! chloric acid "Scheme 33#\ with the a\a!dichloromethylsilane being formed in 76) yield ð53CB0004Ł[ Another report describes alkyl Grignard addition to trichlorosilyldichloromethane\ which yields using methylmagnesium bromide\ trimethylsilyldichloromethane "50)# ð55CB682Ł[ Photochemical addition of silyl radicals to per~uorinated alkenes has also been employed\ UV irradiation of silane in the presence of tetra~uoroethylene giving a 50) yield of 0\0\1\1 tetra~uoroethylsilane in 07 h ð54JCS1090Ł[ Similarly\ photochemical addition of the chlorosilyl radical derived from methyl! dichlorosilane to tetra~uoroethylene results in a 87) yield of the a\a!di~uorosilane adduct ð57ZOB1702Ł[ Lithiation of 0\5!dibromodeca~uorohexane\ followed by addition of trimethylsilyl chloride\ results in formation of 0\5!bis"trimethylsilyl#deca~uorohexane in 55) yield ð58JOM"05#22Ł[ BunLi. –110 °C
Cl
CH2Cl2 + 2 TMS-Cl
TMS
64%
Me Me Si Me
Cl
i, BunLi, –110 °C
Cl TMS
ii, EtOH, –65 °C 73%
Br2, 50 °C, then 80 °C, 12 h
Me
97%
Me
Me
TMS
TMS
Br
Si
Br
Br
Br
HCl
Cl2CHSiCl3 + SiCl4
Cl2(SiCl3 )2 87%
Cl
NCS, CCl4
TMS
SMe OMe
TMS
SMe
TMS
60%
SMe Cl
Cl2, CCl4, Et3N 69%
TMS
OMe
Scheme 44
Preparation of systems containing a metalloid\ halogen and chalcogen have also been reported[ Chlorination of "methylthiomethyl#trimethylsilane has been accomplished\ giving ðchloro! "methylthio#methylŁtrimethylsilane in 59) yield "Scheme 33# ð78T526Ł[ Additionally\ ðmethoxy"methylthio#methylŁtrimethylsilane "itself prepared from ðchloro"methylthio#methylŁ trimethylsilane by addition of sodium methoxide# has been converted to ðchloro"methoxy# methylŁtrimethylsilane "Scheme 33# in 58) yield\ using traditional chlorination conditions ð78T526Ł[ 5[91[2[1 Halogen and Boron Derivatives Compounds of this class are extremely unstable\ which accounts in part for their general lack of utility in synthesis[ The general mechanism for the decomposition of a!bromoalkylboranes "formed from trialkylboranes and bromine# appears to involve HBr!induced cleavage which may proceed via a radical pathway\ rather than by simple rupture of the C0B bond ð69JA6101Ł[ Treatment of a\a!dihaloalkylboranes with nucleophiles such as water also induces rearrangement\ providing a route\ after oxidation\ to secondary alcohols ð60JA1685Ł[ An a\a!dichloroalkylborane was prepared by Seyferth by dichlorocarbene insertion into a trialkylborane "Scheme 34#^ however\ spontaneous rearrangement occurred with subsequent elimination from the chloroborane species ð55JA0723Ł[ It is reported that the stability of the intermediate a\a!dichloroalkylborane is a function of the borane R group\ and that triarylboranes "R Ph# yield the more stable adducts[
R3B
70 °C, 40 min
R=
Prn,
R
PhHgCCl2Br
Bun,
R
R
B
R
Cl
Cl
Ph Scheme 45
Cl
B
R
Cl
R
51
Halo`ens and any other Elements
5[91[2[2 Halogen and Germanium Derivatives Trichlorogermane has been shown to undergo addition to chlorinated alkenes\ and this constitutes an excellent route to a\a!dichloroalkylgermanes "Scheme 35# ð59DOK"020#87Ł[ Photochemical chlori! nation of alkylgermanium compounds has also been reported\ giving moderate yields of the a\a! dichloro species "Scheme 35# ð56ZOB0939Ł[ Bis"per~uoroalkyl#mercury compounds have been shown to react with germanium tetrahalides to produce per~uorogermanium alkyls in good yield "Scheme 35# ð67JA0611Ł[ The trihalo"per~uoroalkyl#germanium compounds produced are versatile synthetic intermediates\ since they react with dialkylcadmium reagents to give alkyl "per~uoro! alkyl#germaniums ð67JA0611Ł[ Bis"triethylgermyl#mercury undergoes exchange with bis"halo! alkyl#mercury compounds\ to yield mixed haloalkyl "triethylgermyl#mercurials ð61JOM"23#188Ł[ These mixed mercurials react with caesium ~uoride to produce haloalkyl germaniums in good yield "Scheme 35# ð61JOM"23#188Ł[ Bis"trialkylgermyl#mercury reacts with bis"haloalkyl#mercury compounds to produce a variety of mixed haloalkyl germanium species ð61IZV74Ł[ The intermediate is presumably a mixed "triethylgermyl#mercury species\ and the isolated yields are good to excellent ð61IZV74Ł[ Cl
Cl
Cl
Cl
F3C
Cl HGeCl3, 80 °C, 2 h 48%
GeCl3
Cl Cl
Cl2, hν
GeCl3
58%
GeCl3
F3C Cl
CsF, THF, 5 min
Et
75%
Et
Et3GeHgC2F5
Et
75%
Et
Et3GeHgCFClCF3
(C2F5)2Hg
GeBr4, 195 °C
Br
45%
Br
Ge
(C2F5)2Hg
I
53%
I
CF3 F
Et Ge
CF3
Cl
F
Br Ge F
GeI4, 135 °C
Cl
Et
F CsF, THF, 5 min
Cl
CF3 F
I Ge F
CF3 F
Scheme 46
5[91[3 FUNCTIONS CONTAINING HALOGEN AND A METAL AND POSSIBLY A GROUP 04 ELEMENT\ A CHALCOGEN OR A METALLOID 5[91[3[0 Halogen and Lithium Derivatives Under the general heading of {lithium carbenoids|\ haloalkyllithium compounds have enjoyed widespread use due to their unusual reactivity and their ability to deliver the versatile halomethylene functional group to suitable acceptors[ A critical aspect of these species is the role of solvent used in their preparation\ THF being the solvent of choice\ owing to its ability to stabilize the carbenoid species[ However\ the increased viscosity of THF at the low temperatures typically employed to generate carbenoids sometimes poses problems\ and often ether or petroleum ethers are used as co! solvents[ Typical conditions involve treating a dilute solution of either a dihaloalkane or a tri! haloalkene at −099>C with an alkyllithium reagent in THF "Scheme 36# ð54JA3036\ 54TL858\ 82T7376Ł[ Since the carbenoids are typically thermally unstable "decomposing completely above −54>C#\ in
52
Halo`en and a Metal
situ reaction with a suitable electrophile is usually carried out\ otherwise intramolecular carbenoid insertions may take place[ Examples of lithiodi~uoroalkanes are common\ available either by metallation of di~uoroiodoalkanes at low temperature ð74TL4132Ł or by metallation of di~uoro! alkanes with lithium amide bases at elevated temperature ð66JOC454Ł[ Terminal lithioper~uoro! alkanes often undergo spontaneous elimination of LiF to yield per~uorinated alkenes ð74TL4132Ł[ The alkoxycarbenoid ClCH1CH1OCHClLi has been generated and used to cyclopropanate cyclo! hexene ð58OS"38#75\ 61JA014Ł[ I
LDA, –78 °C, THF, 30 min
CH2I2
Li
I BuLi, THF, –100 °C
PhCCl3
Cl
Ph
Li
Cl Scheme 47
5[91[3[1 Halogen and Magnesium Derivatives Transmetallation reactions between Grignard reagents and perhalogenated systems is a versatile route to compounds of this class[ Thus phenylmagnesium bromide reacts with 0!iodohepta~uoro! propane at low temperature to produce hepta~uoropropylmagnesium bromide in good yield "Sch! eme 37# ð46JA2240Ł[ Such Grignard reagents are useful for addition of perhaloalkyl functionality to carbonyl compounds ð77BCJ2210Ł[ Other examples of this transmetallation protocol demonstrate its synthetic utility "Scheme 37# including formation of bis"bromomagnesium# compounds ð64JFC"4#364Ł[ F
F
PhMgBr, –78 °C, Et2O
I
F3C F
F
F
F MgBr
F3C
F
F I
F
F
2 RMgBr, –70 °C, Et2O
F
BrMg
F
+ PhI
F
F
I F
F
MgBr
F
F
F
F
Scheme 48
5[91[3[2 Halogen and Copper Derivatives Reaction of copper metal with terminally iodo!substituted per~uoroalkanes at elevated tem! peratures results in formation of a per~uorinated alkylcopper"I# species\ together with copper"I# iodide "Equation "06## ð76JFC"26#060Ł[ Chain polymerization of these species has been reported on thermolysis in DMF ð77DIS"B#1862Ł[ F F3C
I
F
2 Cu, DMSO, 110 °C
F
F3C
Cu
+ CuI
(17)
F
5[91[3[3 Halogen and Silver Derivatives Addition of silver tri~uoroacetate to chlorotri~uoroethene in the presence of metal ~uorides results in the formation of an organosilver compound bearing an a\a!dihalo alkyl group "Equation
53
Halo`ens and any other Elements
"07## ð62JOM"46#312Ł[ Caesium ~uoride is reported to promote this reaction more e.ciently than other alkali metals[ F
F
F
Cl
CF3CO2Ag, MF
Cl
Ag
(18)
F
F3C
5[91[3[4 Halogen and Zinc Derivatives Zinc metal reacts with alkyl iodides\ chlorides and bromides to give the corresponding halozinc reagents "Scheme 38# ð42JCS2596\ 46JA3048\ 73JFC"15#324\ 77JOM"228#06Ł[ Yields of organozinc reagent are heavily dependent on both concentration and temperature of reaction and\ where ethers are not employed as solvents\ solvated products are formed\ for example\ with DMF[ F
F
F3C
I
F
F3C
Cl
F
F3C
75%
F Cl
F
Zn, dioxane
ZnI
F Cl
Zn, DMF
Cl
F3C
F
ZnCl(DMF)2 Cl
Scheme 49
5[91[3[5 Halogen and Cadmium Derivatives Cadmium metal will insert between the carbonÐbromine or carbonÐiodine bond in mixed per! haloalkanes to yield a variety of organocadmium reagents "Scheme 49# ð77JFC"28#314\ 77JFC"30#074Ł[ Alternatively\ transmetallation from dialkylcadmium reagents to dihaloiodoalkanes can be employed to form perhalodialkylcadmium reagents of this class[ F F
2 F5C2I
F
Cd, DMF, 50 °C
X
X = Br, 75%; I, 91%
Me2Cd, MeCN
F F3C
Cd-X
F F
F Cd
F
+ 2 MeI
CF3
Scheme 50
5[91[3[6 Halogen and Mercury Derivatives Mercuric ~uoride will add to haloalkenes quite readily at elevated temperatures to yield per! halodialkylmercury compounds "Scheme 40# ð59JOC094\ 50JCS2714Ł[ Strict regiocontrol in the addition reactions to mixed haloalkenes is usually observed[ It has been reported that per~uoro! propen!1!ol\ the meta!stable enol form of penta~uoroacetone\ reacts with mercury tri~uoroacetate
54
Halo`en and a Metal
to yield tri~uoroacetoxymercuricper~uoroacetone "Scheme 40# ð64DOK"110#0220\ 65ZOR0266Ł[ Care must be taken when handling this species\ as it is reported to undergo rapid hydration to form the corresponding hydrate[ F
F
F
F
F
Cl
HgF2, HF, ∆
Cl
Cl
69%
F3C
F
HgF2, 100 °C
F
56%
F
CF3
(CF3CO2)2Hg, Et2O
F
OH
20 °C, 12 h 79%
F
Hg
F3C
F
F
Cl
CF3 Cl
Cl
Hg
CF3
CF3CO2HgCF2COCF3
Scheme 51
5[91[3[7 Halogen and Tin Derivatives Reaction of dialkyltin hydrides with tetra~uoroethylene is reported to give the 0 ] 1 adducts "Scheme 41# ð54AFC"3#49Ł[ Another route to these compounds is via insertion to iodoper~uoro! alkanes using either tin"II# chloride or tin"II# ~uoride "Scheme 41#[ The resulting organotin com! pounds retain the halogen atoms originally attached in this rapid reaction ð70CL0226Ł[ Reaction of trimethyltin hydride with trialkyl"tri~uoromethyl#stannanes results in reduction to the cor! responding di~uoroalkyltin species "Scheme 41# ð69IC0571Ł[ Bis"per~uoroalkyl#cadmium com! pounds are reported to undergo transmetallation with Me2SnOCOCF2 to yield the corresponding per~uoro organotin derivatives "Scheme 41# ð74JFC"16#298Ł[ Tetrakis"tri~uoromethyl#germanium is reported to react with trimethyltin hydride to produce\ in addition to tris"tri~uoromethyl#germane\ trimethyl"di~uoromethyl#tin in low yield ð83JOM"354#042Ł[ F
F
F
F
Bu2SnH2
F
F
F3C(CF2)5I
SnCl2 (or SnF2), DMF, 25 °C
Me3SnCF3
Me3SnH, 150 °C
F F
F
Sn F Bu Bu F
F
F3C(CF2)5SnCl2I
Me3SnCHF2
63%
(C2F5)2Cd
Me3SnOCOCF3, 70 °C
Me3SnC2F5
64%
Scheme 52
5[91[3[8 Halogen and Lead Derivatives Addition of tetramethyllead to iodopenta~uoroethane at elevated temperature results in for! mation of penta~uoroethyltrimethyllead in moderate yield "Scheme 42# ð59JA5117Ł[ In an analogous manner to the corresponding organotin compounds\ bisper~uoroalkyl cadmium species undergo
55
Halo`ens and any other Elements
transmetallation with Me2PbOCOCF2 to yield per~uoro organolead derivatives "Scheme 42# ð74JFC"16#298Ł[ CF3CF2I
Me4Pb, 150 °C
Me3PbCF2CF3
28%
(C2F5)2Cd
Me3PbOCOCF3, 70 °C
Me3PbC2F5
91%
Scheme 53
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
Comprehensive Organic Functional Group Transformations
6.03 Functions Containing Three Chalcogens (and No Halogens) GLYNN MITCHELL ZENECA Agrochemicals, Bracknell, UK 5[92[0 INTRODUCTION
57
5[92[1 FUNCTIONS BEARING THREE OXYGEN ATOMS 5[92[1[0 Methods for the Preparation of Carboxylic Ortho!esters and Related Compounds 5[92[1[0[0 Ortho!esters from 0\0\0!trihaloalkanes\ a\a!dihalo ethers and a!haloacetals 5[92[1[0[1 Ortho!esters from imidate ester salts 5[92[1[0[2 Ortho!esters from carboxylic acids and derivatives 5[92[1[0[3 Ortho!esters from dioxocarbenium salts 5[92[1[0[4 Ortho!esters from 0\0!dialkoxyalkenes\ 0\0!dihaloalkenes and 0!alkoxyalkynes 5[92[1[0[5 Ortho!esters from 0\0!dialkoxycyclopropanes and related compounds 5[92[1[0[6 Ortho!esters from acetals 5[92[1[0[7 Ortho!esters from ortho!carbonate esters and trialkoxyacetonitriles 5[92[1[1 Preparation of Carboxylic Ortho!Esters from Other Ortho!Esters 5[92[1[1[0 Trans!esteri_cation reactions 5[92[1[1[1 Modi_cation of R0 and R1 of R0C"OR1#2 5[92[2 FUNCTIONS BEARING THREE SULFUR ATOMS 5[92[2[0 Methods for the Preparation of Trithio!ortho!esters and Related Compounds 5[92[2[0[0 Trithio!ortho!esters from RC"X0#"X1#X2 5[92[2[0[1 Trithio!ortho!esters from thioimidate ester salts 5[92[2[0[2 Trithio!ortho!esters from carboxylic acids and derivatives 5[92[2[0[3 Trithio!ortho!esters from dithio! and trithiocarbenium salts 5[92[2[0[4 Trithio!ortho!esters from dithioacetals 5[92[2[0[5 Trithio!ortho!formates from trithiocarbonates 5[92[2[0[6 Trithio!ortho!formates from tetrathio!ortho!carbonates 5[92[2[1 Preparation of Trithio!ortho!esters from other Trithio!ortho!esters 5[92[2[1[0 Hi`her trithio!ortho!esters from trithioformate esters 5[92[2[1[1 Trans!esteri_cation of trithio!ortho!esters 5[92[2[1[2 Modi_cation of R0 and R1 of R0C"SR1#2 5[92[2[2 Methods for the Preparation of Oxidised Derivatives of Trithio!ortho!esters 5[92[2[2[0 Oxidised trithio!ortho!esters containin` at least one sulfoxide `roup 5[92[2[2[1 Oxidised trithio!ortho!esters containin` at least one sulfone `roup 5[92[2[2[2 Oxidised trithio!ortho!esters containin` at least one sulfonate `roup 5[92[3 FUNCTIONS BEARING THREE SELENIUM ATOMS 5[92[3[0 Methods for the Preparation of Triseleno!ortho!esters 5[92[3[0[0 Triseleno!ortho!esters from RC"X0#"X1#X2 5[92[3[0[1 Triseleno!ortho!esters from carboxylic acids 5[92[3[0[2 Triseleno!ortho!esters from triselenocarbenium salts 5[92[3[0[3 Triseleno!ortho!esters from diselenoacetals and related compounds 5[92[3[0[4 Triseleno!ortho!formates from tetraseleno!ortho!carbonates 5[92[3[0[5 Hi`her triseleno!ortho!esters from triseleno!ortho!formate esters
57 57 57 58 60 62 63 65 66 66 67 67 79 70 70 70 72 73 74 74 76 76 77 77 77 78 89 89 89 80 80 81 81 81 82 82 82 83
5[92[4 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN
84
5[92[4[0 Methods for the Preparation of Functions R0C"OR1#"OR2#SR3 5[92[4[0[0 From R0C"X0#"X1#X2
84 84
56
57
Three Chalco`ens 5[92[4[0[1 From monothiocarboxylic esters 5[92[4[0[2 From dioxo! and oxothiocarbenium salts 5[92[4[0[3 From monothioacetals and related compounds 5[92[4[0[4 From 1!alkoxythiophenes 5[92[4[1 Methods for the Preparation of Functions R0C"OR1#"SR2#SR3 5[92[4[1[0 From R0C"X0#"X1#X2 5[92[4[1[1 From dithiocarbenium salts 5[92[4[1[2 From mono! and dithioacetals and related compounds 5[92[4[1[3 Miscellaneous methods 5[92[4[2 Methods for the Preparation of Functions R0C"OR1#"OR2#SeR3 5[92[4[2[0 From 1!alkoxyselenophenes 5[92[4[3 Methods for the Preparation of Functions R0C"OR1#"SeR2#SeR3 5[92[4[3[0 From R0C"X0#"X1#X2 5[92[4[4 Methods for the Preparation of Functions R0C"OR1#"SR2#SeR3 5[92[4[4[0 From monothioacetals and related compounds
5[92[5 MIXED SULFUR AND SELENIUM FUNCTIONS
85 85 86 86 86 86 87 87 88 099 099 099 099 099 099 090
5[92[5[0 Methods for the Preparation of Functions R0C"SR1#"SR2#SeR3 5[92[5[0[0 From R0C"X0#"X1#X2 5[92[5[0[1 From selenodithiocarbenium salts 5[92[5[0[2 From dithioacetals 5[92[5[1 Methods for the Preparation of Functions R0C"SR1#"SeR2#SeR3 5[92[5[1[0 From diseleno!ortho!esters
090 090 090 091 091 091
5[92[0 INTRODUCTION The scope of this chapter is intended to cover the synthesis of compounds bearing the C"X#"Y#Z group in which each of X\ Y and Z are independently linked through O\ S\ Se and Te atoms[ However\ at the time of writing no such compounds containing Te had been reported in the literature\ so the discussion is limited to O\ S and Se containing compounds[
5[92[1 FUNCTIONS BEARING THREE OXYGEN ATOMS Carboxylic ortho!esters contain a carbon atom bearing three alkoxy or aryloxy groups[ Closely related to these are the corresponding acyloxy esters "bearing at least one RCOO group#\ peroxy esters "bearing at least one ROO group# and aminoxy esters "bearing at least one R0R1NO group#[ Ortho!esters which contain one or more hydroxy groups are generally unstable and decompose to carboxylic esters and alcohols\ though a few examples are known in which ortho!hydrogen esters are stabilised by electronic and:or ring strain e}ects ð15BSB301\ 54T1948\ 79JOC1985Ł[ Methods for the preparation of ortho!esters and related compounds have been reviewed by Post ðB!32MI 592!90Ł\ DeWolfe ðB!69MI 592!90\ 63S042Ł\ Sandler and Karo ðB!75MI 592!90Ł and Simchen ð74HOU"E4#2Ł[ Other reviews concentrate on the reactions of ortho!esters ðB!58MI 592!90\ 75UK0792Ł\ and on their use in polymerisation reactions ð74MI 592!90Ł[
5[92[1[0 Methods for the Preparation of Carboxylic Ortho!esters and Related Compounds 5[92[1[0[0 Ortho!esters from 0\0\0!trihaloalkanes\ a\a!dihalo ethers and a!haloacetals Williamson and Kay reported the _rst synthesis of triethyl and tripentyl ortho!formates by reaction of the appropriate sodium alkoxide with chloroform "Equation "0## ð0743LA"81#235\ 0743PRS024Ł[ This procedure has since been used to prepare a number of simple trialkyl ortho!formates ð0768CB004\ 21JA1853\ 22JA2740\ 53RTC008Ł[ The reaction is carried out either by adding chloroform to the alkoxide\ or by adding sodium metal to a mixture of the alcohol and chloroform^ a typical procedure is described in Or`anic Syntheses for the preparation of triethyl ortho!formate ð40OSC"0#147Ł[ Yields are generally low "29Ð34)#\ irrespective of the method used[ CHCl3
NaOR
OR (1)
RO OR
58
Three Oxy`ens
The use of ~uorodichloromethane or di~uorochloromethane in place of chloroform has been reported to give higher yields of ortho!formates ð46JA4382\ 59JA0287Ł[ Carbon tetrachloride and dichlorodi~uoromethane have also been shown to give ortho!formates on reaction with sodium alkoxides ð10JCS0111\ 47USP1742420Ł\ these reactions proceeding via the corresponding haloforms which are generated in situ under the alkaline conditions[ Triaryl ortho!formates are not obtained in appreciable amounts from the reaction of activated phenols with chloroform since the preferred pathway is that of the ReimerÐTiemann reaction^ less activated phenols do give ortho!formates\ but yields are generally poor ð0771CB1574\ 13JA1989\ 44JA5533Ł[ The Williamson synthesis has been extended to the preparation of certain higher ortho!esters^ trialkyl ortho!benzoates "0# ð31JA1414\ 49JA0550Ł and heterocyclic analogues\ for example "1# ð79LA0105Ł\ and trialkyl and triaryl ortho!esters of perhalogenated!acrylates "2# ð56CB1835\ 60ZOR1050Ł and !crotonates "3# ð59IZV120Ł have all been prepared from the appropriate trichloro! methyl compounds[ However\ the general utility of the method for the synthesis of ortho!esters from trihalomethyl compounds bearing a!hydrogen atoms is limited\ since these substrates may also undergo competing elimination reactions under the strongly basic reaction conditions ðB!69MI 592! 90\ 63S042Ł[ Ar
OR OR OR
Cl
N N (MeO)3C
S
C(OMe)3 Cl
(2)
(1)
F
OR
Cl OR
F
Cl
OR
Cl
OR
F (4)
(3)
OR
OR
A variation of the Williamson synthesis was reported by Hill et al[ ð54JOC300Ł\ who obtained ortho!formates "4\ R H# and ortho!benzoates "4\ R Ph# derived from ~uorinated alcohols\ which do not undergo the base promoted reaction\ by the iron"III# chloride catalysed reaction of the alcohol with chloroform and a\a\a!trichlorotoluene respectively "Equation "1##[ Cl Cl Cl
R
Rf
OH
, FeCl3 cat.
R
62–80%
OCH2Rf OCH2Rf OCH2Rf (5)
(2)
Nucleophilic displacement of the halogen atoms of a\a!dihalo ethers and a!haloacetals with alkoxides also gives ortho!esters[ In these cases\ mixed ortho!esters "5#\ in which R1 and R2 are di}erent\ may be obtained "Scheme 0# ð24CB1040\ 47JPR59\ 50CB427Ł[ The cyclic diacyloxy ester "6# was obtained from a\a!dichlorophthalide and 2!hydroxybutanoic acid "Equation "2## ð43LA"476#115Ł[ R1
OR2 Cl Cl
OR2 OR3 OR3 (6) Scheme 1
NaOR3
R1
NaOR2
OR3 OR3 Cl
R1
a\a!Dihalo ethers and a!haloacetals may form as intermediates in the reactions between activated 0\0!dihaloalkenes and alkoxides which yield ortho!esters^ these are discussed in Section 5[92[1[0[4[ O O
OH CO2H , PhNMe , 20 °C 2
O Cl
45%
Cl
O O
(3)
O O
(7)
5[92[1[0[1 Ortho!esters from imidate ester salts Imidate ester salts are transformed into ortho!esters by reaction with alcohols "Equation "3##[ The reaction is normally carried out using imidate ester hydrochloride salts\ which are prepared by the
69
Three Chalco`ens
hydrogen chloride promoted addition of alcohols to nitriles\ and the two!step sequence "nitrile to ortho!ester# is named after Pinner\ who _rst described the preparation of a series of trialkyl ortho! formates using this procedure ð0772CB241\ 0772CB0532Ł[ The method is widely applicable to the synthesis of ortho!formic and higher aliphatic ortho!esters^ yields are generally in the 59Ð79) range\ but are lower "29) or less# for aliphatic ortho!esters bearing two substituents a! and:or b! to the ester function ð31JA0714\ 40JA1122Ł[ Ortho!benzoate esters may be prepared from benzimidate ester hydrochlorides\ but reported yields are low ð63S042Ł[ The procedure is normally used for the preparation of trialkyl ortho!esters "7# in which R1 and R2 are the same\ but is also suitable for the synthesis of mixed ortho!esters in which R1 and R2 are di}erent ð0772CB241\ 0772CB0532\ 22MI 592!90Ł[ OR2 R1
R3OH
OR2 OR3 OR3 (8)
R1
+
NH2 X–
(4)
The simplest procedure for the alcoholysis of an imidate ester is to allow a solution of the imidate ester hydrochloride in an excess of the alcohol to stand at room temperature ð17JA405\ 24JA1379Ł[ However\ reaction times can be long\ and yields are often low[ Improved procedures include heating the imidate ester salt with an excess of the alcohol in diethyl ether ð31JA0714\ 35JA0811Ł\ or petroleum ether ð42JA2876\ 47JA2804Ł[ It is important to maintain strictly anhydrous conditions during these alcoholysis reactions\ since the ortho!ester products are extremely prone to acid!catalysed hydrolysis[ High temperatures also need to be avoided\ as imidate ester hydrochlorides decompose to alkyl chlorides and the corresponding carboxamide at elevated temperatures ð40JA1122Ł[ Ortho!esters may be prepared from nitriles without isolation of the intermediate imidate ester salt[ Erickson synthesised a number of trialkyl ortho!formates in moderate yields "up to 45)# by a one!step process which involved the introduction of hydrogen chloride into a large excess of both hydrogen cyanide and the alcohol ð44JOC0462Ł[ Later workers found that better yields were obtained if the acidity of the reaction medium was reduced to pH 1Ð5 after initial formation of the formimidate ester hydrochloride ð65JAP"K#65097901\ 79JAP"K#7972616\ 73MIP410261Ł[ Other methods for the preparation of ortho!esters which proceed via imidate ester salts have been described[ A variation of the Pinner method involves the alcoholysis of O!methyl imidate salts "8^ Equation "4##\ which are prepared from amides and dimethyl sulfate ð79LA0566Ł[ Ethanolysis of imidoyl chloride salts "09\ R Et\ Ph# produced triethyl ortho!propionate and triethyl ortho! benzoate in yields of 51) and 34) respectively\ via the corresponding O!ethylimidate ester salts ð52CB1560Ł[ Reaction of formamide with benzoyl chloride or ethyl chloroformate in the presence of alcohols gave trialkyl ortho!formates in yields of 39Ð49) "Scheme 1# ð57LA"605#196Ł\ and mixed ortho!esters\ "00# for example\ were similarly obtained by treatment of formamide with benzoyl chloride in the presence of a mixture of a simple alcohol and a diol ð70MI 592!90Ł[ OR2 R1 MeOSO3–
N+
R3OH
R1
OR3 OR3 OR3
(5)
(9)
Cl R N+
Cl–
O EtO O
(10)
O H NH2
R1COCl
O COR1 H
(11)
R2OH
+
NH2 Cl–
OR2 H
+
NH2 Cl– Scheme 2
R2OH
H
OR2 OR2 OR2
60
Three Oxy`ens 5[92[1[0[2 Ortho!esters from carboxylic acids and derivatives "i# From carboxylic acids and esters
Tricyclic ortho!esters are obtained from the reaction of carboxylic acids with 1!alkyl!1!hydroxy! methyl!0\2!dihydroxypropanes "Equation "5## ð46MI 592!90\ 54NEP5301525Ł[ The method works best for carboxylic acids bearing electron withdrawing substituents\ and the reactions are forced to completion by azeotropic removal of water using benzene or xylene[ Ortho!esters derived from diols or simple alcohols are not generally available by this method[ OH HO
O R1
R2 HO
OH
O O
R1
H+
(6)
R2
O
Aliphatic carboxylic esters of 2!methyl!2!hydroxymethyloxetane have been shown to rearrange smoothly to bridged tricyclic ortho!esters in high yield on exposure to boron tri~uoride etherate at temperatures of 9>C or less "Scheme 2# ð72TL4460\ 89JCS"P0#264Ł[ The reaction is postulated to proceed via cyclisation of the zwitterionic species "01#[ O
O
R
BF3•OEt2
O
R
+
66–91%
O – F3B
O
O
R
O O O
(12) Scheme 3
Formate esters react with epoxides in the presence of a catalytic amount of boron tri~uoride to give cyclic ortho!formate esters "Equation "6## ð44AG263Ł[ Acetate esters do not react with epoxides under these conditions[ O H
O
O R2
OR1
R2
R1 O
BF3
(7) O
Ethanolysis of the acetoxy p!toluenesulfonate "02# under basic conditions produced the cyclic ortho!ester "03# ð32JA502Ł[ This product is formed by addition of ethoxide to the intermediate dioxocarbenium ion "04#\ which is itself formed by neighbouring group displacement of tolu! enesulfonate by the acetoxy group "Scheme 3#[ The ortho!ester "05# was formed similarly "Equation "7## ð52PCS263Ł[ Acyloxy ortho!esters were formed by a similar mechanism when acetoxyacyl chlor! ides were treated with alcohols in the presence of triethylamine "Equation "8## ð62JA3905Ł^ the use of alkyl hydroperoxides in place of alcohols produced the analogous peroxy acyloxy ortho!esters in high yields "69Ð099)# ð56AG"E#838Ł[ This method of ortho!ester synthesis has received considerable attention in the _eld of carbohydrate chemistry for the conversion of 0!halo!1!acyloxy carbohydrate derivatives "both furanose and pyranose forms# into the corresponding ortho!esters[ Triethylamine ð89LA388Ł\ 1\5!lutidine ð54CJC0807Ł\ 1\3\5!collidine ð45CB203Ł and silver"I# salts ð60CAR"08#028Ł have been used to catalyse the reactions of 0!halo!1!acyloxy carbohydrate derivatives with alcohols\ and amide acetals ð79MI 592!90Ł and alkoxystannanes ð65CAR"40#C02Ł have been used as alternative sources of the alkoxy group[ The exo!form of the ortho!ester product normally predominates\ and is often formed exclusively[ A representative example is illustrated in Equation "09# ð89LA388Ł[ OTs O
EtOH, KOAc
O
O
+
O
O
(13)
(15) Scheme 4
51%
O (14)
OEt
61
Three Chalco`ens
OTs
O
EtOH, KOAc
(8)
OEt 71%
OAc
O (16)
O
O
O
O Cl
ROH, Et3N
O
42–84%
(9)
O O
OR
Br
O
O
EtOH, Me3N, C6H6
AcO
OAc
37%
(10)
OEt
O
AcO OAc
OAc
Aliphatic O!trimethylsilyl ortho!esters "07\ R alkyl# were obtained from hydroxy esters "06# by deprotonation using a strong base "n!butyllithium or lithium diisopropylamide# followed by reaction with chlorotrimethylsilane "Equation "00## ð80SL059Ł[ This method is not suitable for the preparation of ortho!esters from a!branched carboxylic esters[ O R O
OH Ph Ph Ph
Ph i, BunLi or LiN(Pri)2 ii, TMS-Cl 82–94%
TMS-O R
(17)
O
Ph
O
(11)
Ph
(18)
"ii# From lactones Several examples of the direct formation of ortho!esters from lactones and diols have been reported[ Le Mahieu and Kierstead ð69TL4000Ł described the acid catalysed preparation of the steroid ortho!esters "08\ R H\ Br# from the corresponding lactones and 0\1!dihydroxyethane "Equation "01##\ and Tamaru et al[ ð79BCJ2576Ł prepared the carbohydrate ortho!esters "19#\ "10# and "11# similarly from 1\2\3\5!tetra!O!benzylgluconolactone and the appropriate diol in yields of 66)\ 62) and 32) respectively[ A variation of this method\ which is reported to give higher yields of ortho!esters\ involves the trimethylsilyl tri~uoromethanesulfonate catalysed reaction between lactones and bis!O!trimethylsilyl!0\1!diols[ Yoshimura et al[ ð70CL264Ł prepared the ortho!esters "19#\ "10# and "11# from 1\2\3\5!tetra!O!benzylgluconolactone and the corresponding bis!O!tri! methylsilyl!0\1!diols in yields of 80)\ 78)\ and 53) respectively[ The ortho!ester "12# was obtained in 73) yield from 2\3!dihydrocoumarin and 0\1!bis!O!trimethylsilyloxyethane ð78AJC0124Ł[ HO HO
H H O
O
H
R
HO
H
H
OH , H+, C6H6 56–72%
(12) H
O O
O
H
H
R (19)
Lactones undergo Lewis acid catalysed reaction with epoxides in a similar manner to formate esters to give spirocyclic ortho!esters "Equation "02##[ Lewis acids commonly used are boron tri! ~uoride\ tin"IV# chloride and antimony pentachloride[ The reaction is general\ and has been used to prepare a number of ortho!esters[ Thus\ butyrolactone reacts with 0\1!epoxyethane\ 0\1! epoxypropane\ 0\ 1!epoxy!2!phenoxypropane\ 0\ 1!epoxy!2!"3!methoxyphenoxy#propane\ 0\ 1!epoxy!
62
Three Oxy`ens O
BnO
O O
BnO
O
BnO
O O
OBn BnO
OBn
OBn OBn (21)
(20)
O
O
BnO
O
BnO
O
OBn
O
OBn (22)
O
(23)
0!phenylethane and 0\1!epoxycyclohexane to give the ortho!esters "13\ R H\ Me\ CH1OPh\ CH1OC5H3OMe!p\ Ph# and "14# respectively ð48LA"512#072\ 59GEP0973622\ 71MI 592!90Ł[ O
O
R
O
O
O
Lewis acid
R
O
(13)
O
O O
R
O
O (24)
O (25)
"iii# From dithiocarboxylic esters Dithiocarboxylic esters react with dialkoxystannanes at temperatures of 59Ð84>C to a}ord ortho! esters "Equation "03## ð65CL780Ł[ The method has been used to prepare aliphatic ortho!esters and substituted ortho!benzoate esters\ and reported yields "generally 59) or greater# are favourable compared to some other methods[ S R1 SMe
Bun2Sn(OR2)2, 60–95 °C 45–98%
R1
OR2 OR2 OR2
(14)
5[92[1[0[3 Ortho!esters from dioxocarbenium salts Meerwein et al[ ð45CB1959Ł demonstrated that the O!alkyllactonium tetra~uoroborate salts "15\ R Me\ Et# react with alkoxides to form the cyclic ortho!esters "16\ R Me\ Et# in high yields "Equation "04##[ Ortho!esters derived from the O!ethyl tetra~uoroborate salts of coumarin and 2\3! dihydrocoumarin have been prepared similarly ð54HOU"5#250Ł[ Alkoxides have also been added to dioxolenium tetra~uoroborates "17\ R0 Me\ Ph# and to 1!phenylbenzo!0\2!dioxolium tetra~uo! roborate to give the cyclic ortho!esters "18^ Equation "05## ð59LA"521#27Ł and "29^ Equation "06## ð54AG"E#762Ł respectively[ Several further examples of the addition of alcohols to dioxolenium and dioxenium salts have been described ð56CC02\ 56JOC1529\ 56T3070Ł[
63
Three Chalco`ens +
O
BF4–
NaOR
OR
69–85%
OR OR (27)
(26) O +
O
BF4–
O
NaOR2
R1
+
BF4–
OR2
(16)
O
R1 (29)
(28)
O
(15)
O
NaOR
Ph
O
O
OR
O
Ph
(17)
(30)
5[92[1[0[4 Ortho!esters from 0\0!dialkoxyalkenes\ 0\0!dihaloalkenes and 0!alkoxyalkynes Alcohols and phenols add to 0\0!dialkoxyalkenes "ketene acetals# to give high yields of ortho! esters "Equation "07## ð25JA418Ł[ The reaction is catalysed by acids ð47JA0136Ł\ though ortho!esters are also formed under neutral and basic conditions ð26JA1155\ 31JA0852Ł[ This method is particularly useful for the preparation of hindered ortho!esters\ for example trimethyl ortho!diphenylacetate ð40JA2796Ł\ trimethyl ortho!dimethoxyacetate ð55CB0781Ł and triphenyl ortho!acetate ð34JA549Ł\ which are di.cult to prepare by other methods[ The procedure is also suitable for the synthesis of mixed ortho!esters "20# in which R2 and R3 are di}erent ð25JA418\ 31JA1414\ 53JOC1662Ł^ use of benzaldoximes in place of alcohols or phenols gives rise to aminoxy ortho!ester derivatives "20\ R3 NCHAr# ð50JOC1191Ł[ R1
OR3
R2
OR3
R4OH
R1
OR3 OR3 OR4
R2
(18)
(31)
Activated 0\0!dihaloalkenes undergo reaction with sodium alkoxides\ giving rise to ortho!ester products[ Thus\ ortho!ester "21\ R Me^ X H# was isolated in 68) yield from the reaction between 0\0!dichloro!1!nitroethene with sodium methoxide "Equation "08## ð67BSB582Ł\ "21\ R Et^ X Cl# was obtained in 23) yield from 0\0\1!trichloro!1!nitroethene and sodium ethoxide ð67ZOR1118Ł\ and "22# was prepared from per~uoropropene and sodium methoxide "Equation "19## ð62USP2634119Ł[ It is not known whether these reactions proceed by an additionÐelimination mechanism via a 0\0!dialkoxyalkene intermediate\ or whether they proceed by an additionÐsub! stitution mechanism via a\a!dihaloether and a!haloacetal intermediates[ X
Cl Cl
O2N
NaOR, ROH, 0 °C 34–79%
X O2N
OR OR OR
(19)
OMe OMe OMe
(20)
(32)
F
F
F3C
F
NaOMe, MeOH, 55 °C, 5 h
F F3C (33)
In a reaction related to the addition of alcohols to 0\0!dialkoxyalkenes\ mixed ortho!acetate esters have been prepared by the Lewis acid catalysed addition of alcohols and phenols to 0!ethoxyethyne "Equation "10## ð64RTC198Ł[ Zinc chloride is the preferred catalyst for the reaction with alcohols\ whereas mercury"II# acetate is preferred for phenols[ Triethyl ortho!acetate has also been obtained by treatment of 0!ethoxyethyne with ethanolic sodium ethoxide ð42MI 592!90Ł[ Addition of oximes to 0!ethoxyethyne a}orded the mixed ortho!ester derivatives "23\ R NCR0R1# ð59RTC777Ł[
64
Three Oxy`ens OEt OR (Ar) OR (Ar) (34)
ROH, ZnCl2 or ArOH, Hg(OAc)2
OEt 35–79%
(21)
Tris"b!alkoxyalkyl# ortho!acetates have been obtained by treatment of 0\0!dichloroethene with the appropriate sodium alkoxide ð53JOC1662Ł[ It has been proposed that these reactions proceed through a series of elimination and addition steps via a 0!alkoxyalkyne intermediate "Scheme 4#[ Cl
NaOR
OR
NaOR
Cl
Cl
OR OR OR
NaOR
NaOR
OR 41–57%
Cl Scheme 5
0\0!Dialkoxyalkenes undergo zinc chloride promoted reactions with epoxides to give cyclic ortho! esters "Equation "11## ð68TL1814Ł[ The epoxide generally undergoes attack at the least hindered position\ unless attack at the more substituted position is favoured on electronic grounds[
R1
R1
O
OR2
R3
OR2 R3
ZnCl2 40–60%
OR2
O
(22)
OR2
Triethyl ortho!cinnamate esters have been prepared by addition of ethanol to diethoxyethen! ylidinetriphenylphosphorane "24#\ followed by a Wittig reaction of the resulting phosphorane with aromatic aldehydes ð75S286Ł "Scheme 5#[ A related method for the preparation of a series of unsaturated cyclic ortho!esters "25# involves the addition of an enolised 0\1!diketone to phosphorane "24#\ followed by intramolecular Wittig cyclisation of the intermediate ketophosphorane "Scheme 6# ð72CB0352\ 72CB2371\ 77T4984Ł[ +
–
OEt
Ph3P
OEt (35)
EtOH
+
Ph3P
90%
–
OEt
ArCHO
OEt OEt
42–67%
OEt OEt Ar
OEt
Scheme 6
O
R1
R2
–
(35)
R3
R1 OH
+
O
R1
PPh3 OEt
R2
O R3
46–71%
OEt
OEt
R2 O R3
OEt
(36) Scheme 7
The preparation of cyclic ortho!esters by thermal ð3¦1Ł cycloaddition reactions of 0\0! dialkoxyalkenes and a\b!unsaturated carbonyl compounds was _rst described by McElvain et al[ "Equation "12## ð43JA4625Ł[ Many further examples of ortho!esters "26# have since been prepared by reaction of 0\0!dimethoxyethene\ 0\0!dimethoxy!0!propene\ 0\0!dimethoxy!1!methyl!0!propene\ 0\0\1!trimethoxyethene\ 0\0\1\1!tetramethoxyethene and 1!chloro!0\0!dimethoxyethene with a range of substituted a\b!unsaturated carbonyl compounds ð44JA4590\ 60CC272\ 61CC752\ 70RTC02Ł[ 0\0!Dial! koxyalkenes also undergo ð1¦1Ł cycloaddition reactions with electron de_cient carbonyl compounds\ such as acyl cyanides and aldehydes\ giving rise to the cyclic ortho!esters "27# "Equation "13## ð65JCS"P0#0937\ 66JOC2017Ł[ It has been shown that ð1¦1Ł cycloadducts are the products of the low temperature reaction between 0\0!dialkoxyalkenes and a\b!unsaturated carbonyl compounds\ and that this process is reversible at higher temperature\ when formation of the ð3¦1Ł cycloadducts is favoured on thermodynamic grounds ð70RTC02Ł[
65
Three Chalco`ens R5 R6 R7
R3
R5 R4
R2
heat
R4 R1O
O
OR1
R6
R3 R2
R7
OR1 OR1
O
(23)
(37) O
R2
R3 R1O
OR1
R4
R4
R5
R3 R2
R5
(24)
25–90%
O
OR1 OR1 (38)
A number of _ve!membered ring ortho!esters have been prepared by ð2¦1Ł cycloaddition reac! tions of 0\2!dipoles to 0\0!dialkoxyalkenes[ Some examples are given in Equations "14# ð75JMC442Ł\ "15# ð48G0400Ł and "16# ð55G264Ł[
Ph
Ph
OMe
MeCOCHN2, Cu(acac)3, C6H6, 85 °C, 30 min
OMe 65%
OMe
OMe
Ph
OMe
O But
OMe
N O
(26)
OMe
p-ClC6H4
N+ Ph 125 °C, 16 h 84%
OEt
Ph
O–
Cl
OEt
OMe
ButCNO, 80 °C 30%
(25)
Ph
OEt
N O
(27)
OEt
5[92[1[0[5 Ortho!esters from 0\0!dialkoxycyclopropanes and related compounds Alcohols add to 0\0!dialkoxycyclopropanes which bear an electron withdrawing group "EWG# "carboxylic ester or sulfone# at the 1!position to give ortho!esters "Equation "17## ð62JOC0250\ 74S651Ł[ Mixed ortho!esters "28#\ in which R0 and R3 are di}erent\ have been prepared by this method\ which is analogous to the addition of alcohols to 0\0!dialkoxyalkenes[ Examples of ortho!esters prepared using this procedure are listed in Table 0[ OR1
EWG
OR1 OR1
R4OH, heat
OR1 65–78%
R2
OR4
EWG R2
R3
(28)
R3 (39)
Ring opening of 0\0!dialkoxy!1\1!dichlorocyclopropanes with potassium t!butoxide is accompanied by elimination to produce alkynyl ortho!esters "Equation "18## ð48JA1468Ł[ Addition of alcohols to 0\0!dimethoxycyclopropene produces the unsaturated ortho!esters "39\ R Me\ Et\ Prn\ Pri\ But^ Equation "29## ð66JOC568Ł[ OR1
R2
OR1 Cl
Cl
KOBut
R2
OR1 OR1 OBut
(29)
66
Three Oxy`ens Table 0 Ortho!esters "28# prepared from 0\0!dialkoxypropanes[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Yield R0 R1 R2 R3 EWG ")# Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Me H H Me CO1Et 62 74S651 69 74S651 Et H H Et CO1Et 61 74S651 Me Me H Me CO1Et Et Me H Et CO1Et 65 74S651 67 74S651 Me Et H Me CO1Et Me Ph H Me CO1Et 56 74S651 55 74S651 Me Me Me Me CO1Et Me Me Me Me SO1Ph 54 62JOC0250 60 62JOC0250 Et Me Me Et SO1Ph Et Me Me Me SO1Ph 62JOC0250 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
OMe
OMe OMe
ROH
OMe
(30)
OR (40)
Alcohols also add to 1\1!dialkoxyaziridines and 1\1!dialkoxy!1H!azirines to give a!amino!and a! imino!ortho!esters "30^ Equation "20## ð58TL1112\ 62JMC867Ł and "31^ Equation "21## ð56JA4613Ł respectively[ These compounds are di.cult to prepare by other methods[ OR1 OR1
OR1
R2
OR1
R1OH
R2
N H
(31)
NH2 (41) OR1
R2
OR1
PriOH
OR1 N
OR1 OR1
R2
OPri
(32)
NH (42)
5[92[1[0[6 Ortho!esters from acetals Some acetals undergo electrochemical oxidation in the presence of methanol to give ortho!esters in reasonable yields "Equation "22##[ The reaction has been shown to be successful for 1!alkyl! 0\2!dioxolanes ð67S172Ł\ 1!alkyl! and 1!aryl!0\2!benzodioxoles ð74S20Ł and dimethyl acetals of benzaldehydes ð75T442Ł[ Dimethyl acetals of simple aliphatic aldehydes gave lower yields of ortho! esters\ and the reaction failed completely for the corresponding diethyl acetals ð67S172Ł[ Table 1 lists some representative examples of ortho!esters "32# prepared by this method[ OR2 R1
–2e–(anode), MeOH
R1 OR2
OR2 OR3 OMe (43)
(33)
5[92[1[0[7 Ortho!esters from ortho!carbonate esters and trialkoxyacetonitriles Trialkyl ortho!benzoates have been reported to be formed in up to 66) yield by treatment of the appropriate tetraalkyl ortho!carbonate ester with phenylmagnesium bromide "Equation "23## ð94CB450\ B!32MI 592!90Ł\ and similar syntheses of triethyl ortho!phenylpropiolate ð00BSF0297Ł and triethyl ortho!2!butynoate ð69AG"E#345Ł have been described[ However\ the reaction is not always successful\ and other workers have isolated only ketals and ethers from reactions of ortho!carbonate esters with Grignard reagents ð31JA0714\ 38MI 592!90Ł[ No systematic survey of this method has been
67
Three Chalco`ens Table 1 Examples of ortho!esters "32# prepared by electro! chemical oxidation of acetals[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Yield R1 R2 ")# Ref[ R0 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * H 0"CH1#10 33 67S172 H 0C5H30 38 74S20 53 67S172 Me 0"CH1#10 Me 0C5H30 41 74S20 Pri 0"CH1#10 43 67S172 i 0C5H30 50 74S20 Pr But 0"CH1#10 10 67S172 0C5H30 58 74S20 But 49 74S20 Ph 0C5H30 Ph Me Me 89 75T442 3!ClC5H3 0C5H30 37 74S20 3!ClC5H3 Me Me 73 75T442 0C5H30 33 74S20 3!MeOC5H3 3!MeOC5H3 Me Me 73 75T442 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
carried out\ though DeWolfe ð63S042Ł has suggested that the Grignard reagent needs to bear an electron withdrawing organic moiety for the reaction to work successfully[ RO
OR OR OR
PhMgBr
Ph 77%
OR OR OR
(34)
More recently\ it was reported that trialkyl ortho!benzoate esters are obtained from the reactions of Grignard reagents with trialkoxyacetonitriles "Equation "24## ð70S279Ł[ Trimethyl ortho!benzoate\ trimethyl 1!methyl!ortho!benzoate and triethyl 1!5!di~uoro!ortho!benzoate were prepared in yields of 73)\ 53) and 19) respectively[ Triethyl ortho!phenylpropiolate was prepared in 53) yield from phenylethynyl magnesium bromide and triethoxyacetonitrile using this method ð70S279Ł[ NC
OR OR OR
ArMgX
Ar 20–84%
OR OR OR
(35)
5[92[1[1 Preparation of Carboxylic Ortho!Esters from Other Ortho!Esters 5[92[1[1[0 Trans!esteri_cation reactions Ortho!formate esters undergo exchange reactions on treatment with alcohols "Scheme 7#[ The reaction\ which is acid catalysed\ can be forced to completion by distilling out R0OH "preferably methanol or ethanol# as it is formed\ and a number of trialkyl ortho!formates derived from higher alcohols\ including functionalised alcohols such as 1!chloroethanol and 0!chloro!1!propanol\ have been prepared by this method ð41JA443\ 44JA2790\ 69CB528Ł[ The reaction is subject to steric constraints\ proceeding readily with primary alcohols and less readily with secondary alcohols[ Trans!esteri_cation with tertiary alcohols does not proceed to completion^ treatment of triethyl ortho!formate with t!butanol gave a mixture of t!butyldiethyl and di!t!butylethyl ortho!formates ð52PIA"A#34Ł[ Relatively little has been published on the trans!esteri_cation reactions of higher ortho! esters\ though work that has been reported suggests that these proceed in much the same way as for ortho!formate esters ð49DOK"69#120\ 45ACS0995\ 69CB528Ł[ OR1 R1O OR1
R2OH
OR1 R2O
R2OH
OR1
OR2 R2 O OR1
R2OH
OR2 R2O OR2
Scheme 8
The preparation of mixed ortho!esters by exchange reactions of trialkyl ortho!esters with simple alcohols is not usually feasible since equilibration reactions lead to all possible ortho!ester products
68
Three Oxy`ens
ð22JA2740Ł[ Among the few reported exceptions to this general trend are the reactions of ortho!esters with phenol^ treatment of triethyl ortho!formate and triethyl ortho!acetate with one equivalent of phenol produced good yields of the diethylphenyl ortho!esters "33\ R H\ Me#\ and reaction of triethyl ortho!formate with two equivalents of phenol gave a reasonable yield of the ethyldiphenyl ortho!ester "34^ Scheme 8# ð45ACS0995\ 69CB532Ł[ A recently reported trans!esteri_cation route to mixed ortho!esters\ which is potentially general\ involves the magnesium chloride catalysed exchange reaction with alcohols "Equation "25## ð77TL1912Ł[ Mixed ortho!esters have also been obtained from the O!acyl derivative "35# ð58RTC786Ł\ which was itself prepared by treatment of triethyl ortho! formate with one equivalent of acetic formic anhydride "Scheme 09# ð55RTC682Ł[ In contrast to their reactions with alcohols\ ortho!esters react cleanly with peroxides to form monoperoxy ortho!ester derivatives in high yield ð47CB0831Ł[ OPh
OEt OEt OEt
2 equiv. PhOH, heat
EtO
R (R = H) 51%
OPh (45)
1 equiv. PhOH, heat
R 67–92%
Scheme 9
R1
OEt
OEt OEt OEt
R2OH, MgCl2, CH2Cl2
OR2 OEt OEt
R1
56–96%
OEt
HCO2COMe
EtO 62%
(36)
OEt
ROH, Et3N
RO
AcO OEt
OEt OEt OPh (44)
OEt
48–86%
OEt
(46) Scheme 10
Trans!esteri_cation of simple trialkyl ortho!esters with aliphatic 0\1! and 0\2!diols proceeds cleanly to give mixed cyclic ortho!esters in high yields "Equation "26##[ The reaction is catalysed by acids such as sulfuric acid ð47CB549Ł\ p!toluenesulfonic acid ð69JA473Ł and benzoic acid ð62JA167Ł[ Trans! esteri_cation reactions of trialkyl ortho!benzoates with benzene!0\1!diol proceed in the absence of a catalyst ð54AG"E#762Ł[ Treatment of trialkyl ortho!esters with b!hydroxycarboxylic acids yields cyclic acyloxy ortho!esters "36# ð58TL0936\ 76HCA0219Ł[ In contrast to the equilibration reactions between simple trialkyl ortho!esters and alcohols\ the cyclic ortho!ester "00# reacts moderately cleanly with alcohols to give the exchanged products "37# in yields of 30Ð47) "Equation "27## ð79JCS"P0#645Ł[
R1
OR2 OR2 OR2
HO
OH
R2O
O
R1
O
(37)
R3 R2O
O
R4
R1
O
R4 O
(47)
O OEt O (11)
ROH, H+
O
41–58%
O (48)
OR
(38)
Trialkyl ortho!esters react with conformationally ~exible triols such as glycerol\ 0\2!dihydroxy!1! hydroxymethyl!1!methylpropane and 0\1\3!trihydroxybutane to give good yields of the cor! responding tricyclic ortho!esters "38#\ "49# and "40# respectively ð79MM141\ 79CC196\ 77JA3033Ł\ and exchange with all cis!0\2\4!trihydroxycyclohexane gives high yields of polycyclic ortho!esters "41#
79
Three Chalco`ens
ð42CB689\ 43CB194Ł[ Trans!esteri_cation with conformationally restricted triols normally gives prod! ucts arising from exchange of only two of the alkoxy groups of the ortho!ester[ For example\ exchange with 1\2\4!trihydroxy nucleoside analogues generally leads to exclusive formation of the ortho!ester derived from the 1\2!dihydroxy unit of the triol "Equation "28## ð53CI"L#470\ 56CCC2953\ 74S397Ł[ The trans!esteri_cation method has been used for the preparation of many cyclic\ bicyclic and tricyclic ortho!esters from dihydroxy! and trihydroxy!carbohydrate\ nucleoside and steroid derivatives ðB!69MI 592!90\ 66USP3910348\ 77EUP159868Ł[ R
O R
O
O O
R
O
R
O
(49)
(50)
HO
Het
O O
O O (51)
(52)
O
HOH2C
O
HOH2C
O
O
Het
R1C(OR2)3
(39) O
O
R1
OR2
OH
Ortho!esters have also been prepared by the alcoholysis of amide acetals ð70JOC775Ł and trithio! ortho!esters ð37JA1157\ 79JOC639Ł[
5[92[1[1[1 Modi_cation of R0 and R1 of R0C"OR1#2 Ortho!esters bearing a!hydrogen atoms react with one equivalent of bromine to give a!bromo ortho!esters "42# in up to 79) yield ð26JA0162\ 31JA1414\ 35JA0811Ł^ use of two equivalents of bromine gives a\a!dibromo ortho!esters ð31JA0852Ł[ Dehydrobromination of a!bromo ortho!esters\ "e[g[\ "43##\ to unsaturated ortho!esters\ "e[g[\ "44##\ has been achieved\ but yields are low "08Ð21)# ð62S196\ 74JAP"K#59197872Ł[ Reaction of triethyl ortho!acetate with tri~uoromethylselenenyl chloride gave triethyl a!"tri~uoromethylselenenyl#ortho!acetate\ which was converted to the bis"tri~uoro! methylselenenyl# derivative by deprotonation with sodium hydride\ followed by treatment with a further equivalent of tri~uoromethylselenenyl chloride "Scheme 00# ð81CB460Ł[ Trialkyl ortho! acetates have also been shown to react with perhalogenated aldehydes and ketones\ producing the adducts "45\ R0 H\ CF2\ CClF1^ R1 Me\ Et^ X F\ Cl# in yields of 74Ð83) "Equation "39## ð66ZOR832Ł[
Br R1
OEt OEt OEt
OR3 OR3
Br
OR3 R2 (53)
O O O
O
(54)
(55)
87%
OEt OEt OEt Scheme 11
F X
OR2 OR2 OR2
F3CSeCl, Et2O, –20 °C
F O R1
O O
F3CSe
85–94%
NaH, F3CSeCl
F3CSe
Et2O, –20 °C 97%
F3CSe
F2XC
OH
OR2 OR2
OEt OEt OEt
(40)
OR2
R1 (56)
Dehydrohalogenation of tris"b!chloroalkyl# ortho!esters yielded trialkenyl ortho!esters "Equation
70
Three Sulfurs
"30## ð69CB528Ł[ Ozonolysis of tris"1!propenyl# ortho!formate gave tri!O!acetyl ortho!formate "Equa! tion "31## ð69CB528Ł[ Cl
R2 Cl
R2 R2
O R1
R2
O
KOBut
O
R1
O
O
(41)
O
R2
R2 Cl
O
O3, –78 °C
O
OAc (42)
AcO
60%
O
OAc
5[92[2 FUNCTIONS BEARING THREE SULFUR ATOMS Trithio!ortho!esters contain a carbon atom bearing three alkanethio or arenethio groups[ Related to these are the analogous acylthio esters "containing at least one RCOS group#\ hydrogen esters "containing at least one HS group# and oxidised derivatives bearing sulfoxide\ sulfone and sulfonyl groups[ Methods for the preparation of trithio!ortho!esters and related compounds have been reviewed by Post ðB!32MI 592!90Ł\ DeWolfe ðB!69MI 592!90Ł and Simchen ð74HOU"E4#2Ł[
5[92[2[0 Methods for the Preparation of Trithio!ortho!esters and Related Compounds 5[92[2[0[0 Trithio!ortho!esters from RC"X0#"X1#X2 "i# From 0\0\0!trihaloalkanes and a\a!dihalo ethers Gabriel reported the _rst synthesis of triethyl trithio!ortho!formate and triphenyl trithio!ortho! formate by reaction of the appropriate thiolate salt with chloroform "Equation "32## ð0766CB074Ł[ This method has since been used to prepare a range of trialkyl and triaryl trithio!ortho!formate esters ð0767CB1154\ 22RTC326\ 53CR"148#3940Ł^ yields from reactions with arenethiols are usually high "69) or greater#\ but are lower from reactions with aliphatic thiols[ Bromoform and chloro! di~uoromethane also react with sodium arenethiolate salts to give high yields of triaryl trithio! ortho!esters ð45JA368\ 59JA5007Ł[ Carbon tetrachloride reacts with alkanethiolates to give trialkyl trithio!ortho!esters\ the reactions proceeding via formation of chloroform under the alkaline reaction conditions ð22RTC326Ł[ Tris"tri~uoromethyl# trithio!ortho!formate "46# was prepared by reaction of iodoform with Hg"SCF2#1 "Equation "33## ð56JOC1952Ł[ CHCl3
M+ –SR
SR (43)
RS SR
Hg(SCF3)2, 130 °C
CHI3
SCF3 (44)
F3CS SCF3 (57)
Relatively few reports of the preparation of higher trithio!ortho!esters from 0\0\0!trihaloalkanes have appeared[ 1!Trichloromethylbenzimidazole was converted to the trithio!ortho!esters "47\ R Me\ p!ClC5H3# by reaction with the corresponding thiol ð56JCS"C#29Ł\ and the activated tri! ~uoromethyl group of the thiazole "48# underwent reaction with methanethiol to give the trithio!
71
Three Chalco`ens
ortho!ester "59# ð80JHC0902Ł[ A series of a\a\a!trihalotoluenes have been converted to tris "tri~uoromethyl# trithio!ortho!benzoate esters "50# by treatment with AgSCF2 ð58ZOB0644Ł[ N N H (58)
C(SMe)3 O
CF3
SR SR SR
O
N Cl
S
N
N H (59)
Ar
NEt2
Cl
N H (60)
S
NEt2
SCF3 SCF3 SCF3 (61)
Trithio!ortho!formate esters may also be prepared from dichloromethyl alkyl ethers^ treatment with lead"II# alkanethiolates gives trialkyl trithio!ortho!formates ð50CB427Ł\ whereas reaction with arenethiols in the presence of zinc produces triaryl trithio!ortho!formates ð60ZOR0776Ł "Scheme 01#[ SR2 Pb(SR2)2,
SR2
Et2O
SR2 Cl R1O
ArSH, Zn, Et2O, 35 °C
Cl
SAr
66–92%
ArS SAr
Scheme 12
"ii# From a!halodithioacetals and a!acyloxy! and a!alkoxydithioacetals Treatment of chlorobis"methanethio#methane with methanethiol produced trimethyl trithio! ortho!formate\ though reaction with higher alkanethiols was accompanied by disproportionation\ giving rise to mixtures of trithio!ortho!esters ð50LA"537#10Ł[ Cyclic a!chlorodithioacetals "51\ X S\ CH1# reacted with benzenethiol to give high yields of the trithio!ortho!esters "52\ X S\ CH1^ Equation "34## ð65BCJ442Ł[ Reaction of the benzoyloxytrithiane "53# with a range of alkane! and arene!thiols produced the trithio!ortho!esters "54\ R alkyl\ aryl^ Equation "35## ð63BCJ1346\ 64BCJ1385Ł[ The 1!alkoxybenzodithiole "55# reacted similarly with ethanethiol in the presence of acetic acid to give 1!ethylthio!0\2!benzodithiole "Equation "36## ð64S325Ł[ S
S
PhSH, C6H6, RT
X
Cl
X
S S
S S
S (64)
O S (66)
(45)
S (63)
RSH
OCOPh
S
SPh
80–90%
S (62)
(46)
SR S (65)
EtSH, AcOH, 20 C, 5 h
S
84%
S
SEt
(47)
"iii# From carboxylic ortho!esters and related compounds Carboxylic ortho!formate esters undergo exchange reactions with alkanethiols and arenethiols to give trithio!ortho!esters "Equation "37##[ The reaction may be catalysed using hydrogen chloride ð56AG"E#331Ł\ p!toluenesulfonic acid ð44JA498Ł\ zinc chloride ð53T306Ł\ boron tri~uoride etherate ð61CB2179Ł and montmorillonite KSF ð78SC20Ł\ though it will often proceed in the absence of a
72
Three Sulfurs
catalyst ð59IZV0890Ł[ Exchange of trialkyl ortho!formates with ethanedithiol and propanedithiol gave "56# and "57# respectively ð15JCS1152\ 56AG"E#331Ł\ and exchange of triethyl ortho!formate with 1!methyl!1!thiohydroxymethylpropane!0\2!dithiol produced the tricyclic trithio!ortho!ester "58\ R H# ð44JA498Ł[ Little work has been reported on the exchange of higher ortho!esters with thiols\ though triethyl ortho!acetate does undergo reaction with 1!methyl!1!thiohydroxymethylpropane! 0\2!dithiol to give the tricyclic trithio!ortho!ester "58\ R Me# ð44JA498Ł[ OR1
SR2
R2SH
R1O
(48)
R2S
OR1
S S
S
SR2
S
S
S
S
S
S
S
S
S
(67)
S S
R
S (69)
(68)
5[92[2[0[1 Trithio!ortho!esters from thioimidate ester salts Thioimidate ester hydrochloride salts react with alkanethiols and arenethiols to yield the trithio! ortho!esters "69# ð42JA0557\ 51JOC1747Ł[ Although this method is analogous to the widely used Pinner synthesis of ortho!esters\ relatively few reports of the preparation of trithio!ortho!esters using this procedure have appeared[ Some trithio!ortho!esters prepared by this method are listed in Table 2[ SR2 R1
R3SH
R1
+
NH2 Cl–
SR3 SR3 SR3 (70)
(49)
Table 2 Trithio!ortho!esters "69# pre! pared from thioimidate ester hydro! chloride salts[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ R2 Ref[ R0 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * H Ph 42JA0557 C1F4 Me 51JOC1747 Me 51JOC1747 C2F6 C2F6 Et 51JOC1747 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
Other methods for the preparation of trithio!ortho!esters which proceed via thioimidate inter! mediates have been described[ Formamide undergoes an acid catalysed reaction with thiols to give trithio!ortho!esters "Scheme 02# ð96CB0639\ 96LA"242#020Ł\ and the formanilide "60# reacts with phosphorus oxychloride in the presence of thiols to give trithio!ortho!esters in yields of 33Ð58) "Scheme 03# ð59IZV0717Ł[ Acetamide derivatives do not react under similar conditions ð48RTC243Ł[ O
RSH
H NH2
SR
RSH
H NH
SR RS SR
Scheme 13
O H
(71)
H
+
+
N Ph Cl–
N Ph Me
SR
Cl H
N Ph Cl– Me
Me Scheme 14
SR 44–69%
RS SR
73
Three Chalco`ens
5[92[2[0[2 Trithio!ortho!esters from carboxylic acids and derivatives "i# From acyl chlorides and anhydrides A general method for the preparation of trithio!ortho!esters involves the treatment of acyl chlorides with thiols in the presence of zinc chloride or aluminium trichloride "Equation "49##[ This procedure has been used to prepare a range of trithio!ortho!esters derived from aliphatic ð48RTC243Ł and aromatic ð42JA0557\ 79JOC639\ 75TL3750Ł acyl chlorides^ yields are usually greater than 39)[ A limitation of the method is that acyl chlorides containing one or more a!hydrogen atoms give poor yields of trithio!ortho!esters due to competing elimination reactions\ though this problem can be overcome to some extent by using an excess of the thiol reagent ð48RTC243Ł[ Reaction of acetic anhydride with 2!methylbenzenethiol in the presence of boron tri~uoride has been reported to give tris"2!methylphenyl# trithio!ortho!actetate in 29) yield ð42JA0557Ł[ O
SR2 SR2 SR2
R2SH, ZnCl2 or AlCl3, heat
R1
R1 Cl
(50)
"ii# From carboxylic esters and thioesters In 0896\ Holmberg ð96CB0639\ 96LA"242#020Ł discovered that formate esters undergo an acid pro! moted reaction with alkanethiols and arenethiols to give trithio!ortho!esters "Equation "40##[ A range of trialkyl and triaryl trithio!ortho!formates have been prepared using this method ð96CB0639\ 96LA"242#020\ 37JCS576\ 51RTC0998Ł[ These reactions simply involve saturating a mixture of the ester and thiol with hydrogen chloride\ and allowing the mixture to stand^ yields are normally greater than 49)[ Triaryl ortho!formates have also been obtained from the reactions of arenethiomagnesium bromides with ethyl formate ð51ZOB634Ł[ O
SR2
R2SH, HCl
H
(51)
R2S OR1
SR2
The Holmberg method is not suitable for the preparation of trithio!ortho!esters from higher carboxylic esters[ In a modi_cation of the reaction\ triethyl trithio!ortho!acetate has been obtained in low yield from the zinc chloride catalysed reaction of ethanethiol with ethyl acetate ð48RTC243Ł[ More recently\ the synthesis of trialkyl trithio!ortho!benzoate esters by the aluminum trichloride catalysed reaction of methyl benzoates with alkanethiotrimethylsilanes has been reported "Equation "41## ð79JOC639\ 75TL3750Ł[ O Ar
RS-TMS, AlCl3
Ar
OMe
SR SR SR
(52)
Thiocarboxylic esters "61\ R0 H\ alkyl\ aryl# undergo acid or Lewis acid catalysed reactions with thiols to give trithio!ortho!esters ð34USP1278042\ 42JA0557\ 64JOC852Ł[ Mixed trithio!ortho!esters "62#\ in which R1 and R2 are di}erent\ may be prepared by this method "Equation "42## ð34USP1278042\ 42JA0557Ł[ O R1
R3SH
R1 SR2 (72)
HCl or ZnCl2 or BF3
SR2 SR3 SR3 (73)
(53)
"iii# From carboxylic acids Formic acid reacts with alkanethiols and arenethiols to give trithio!ortho!formate esters ð00CB2124\ Higher carboxylic acids do not generally undergo this reaction^ exceptions are the reactions of tri~uoroacetic acid with ethane!0\1!dithiol and propane!0\2!dithiol\ which give the 01CB1831Ł[
74
Three Sulfurs
cyclic bistrithio!ortho!esters "63# and "64# respectively ð56CC0978\ 57JOC1493Ł[ Reaction of formic acid with hydrogen sul_de and acetic anhydride in the presence of zinc chloride a}orded tris "acetylthio#methane "65^ Equation "43## in 39) yield ð65CS011Ł[ This compound may also be prepared by treatment of formic acid with thioacetic acid and acetic anhydride in the presence of zinc chloride ð65CS011Ł[ S
CF3 S S
S
CF3 S
CF3 S
S
S
S
S
S
CF3
S
(75)
(74)
SAc
H2S, (MeCO)2O, ZnCl2, MeCO2H, 20–50 °C, 2 h
HCO2H
(54)
AcS
40%
SAc (76)
5[92[2[0[3 Trithio!ortho!esters from dithio! and trithiocarbenium salts Trithio!ortho!esters and related compounds are obtained from the addition of thiols and other sulfur nucleophiles to dithiocarbenium salts[ Reaction of the dithiolium tetra~uoroborate salt "66# with sodium benzenethiolate produced the 1!phenylthio!0\2!dithiole "67^ Equation "44##\ and reaction with N\N!dialkyldithiocarbamate salts gave 1!dithiocarbamoyldithioles "68# ð58CPB0820Ł[ Treatment of the dithiolium perchlorate salt "79# with one equivalent of potassium ethyl xanthate yielded the analogous ethoxythiocarbonythio derivative "70#\ whereas the use of an excess of potassium ethyl xanthate produced the sul_de "71#\ the reaction being thought to proceed via further reaction of "70# with the xanthate "Scheme 04# ð66JOC0432Ł[ S Ph
+
SCSNR1R2
S
Ph
EtOCS2K
S
Ph S
EtO S
S
Ph S
S ClO4–
Ph
S (80)
S– SCSOEt
(55)
SPh
S (78)
S +
(79)
(81)
Ph
66%
S (77)
S Ph
S
NaSPh, EtOH, 78 °C, 1 h
BF4–
SCSOEt S (81)
Ph S
(80)
S
–EtOCSSCSOEt
S–
S
Ph
S S (82) Scheme 15
1!Methanethio!0\2!dithiolium salts may be reduced to 1!methanethio!0\2!dithioles using sodium borohydride[ The dithiole "73# was prepared in 67) yield from the salt "72# by this method "Equation "45## ð81JOC0585Ł[ MeSe
S +
MeSe
SMe BF4–
MeSe
S
MeSe
S
NaBH4, MeCN, 20 °C, 1 h
S (83)
SMe
(56)
(84)
5[92[2[0[4 Trithio!ortho!esters from dithioacetals Dithioacetals may be converted into trithio!ortho!esters by deprotonation with a strong base\ followed by reaction of the metallated species "74# with a disul_de "Scheme 05#[ The reaction was
75
Three Chalco`ens
_rst described by Frohling and Arens ð51RTC0998Ł\ who prepared triethyl trithio!ortho!benzoate in 65) yield from benzaldehyde diethyl dithioacetal using sodium amide and diethyl disul_de "Equa! tion "46##[ A procedure for the preparation of trithio!ortho!ester "75# from the cyclic dithioacetal "76# using n!butyl lithium and dimethyl disul_de is given in Or`anic Syntheses ð66OS"45#7Ł\ and this method has also been used for the preparation of a range of benzoic\ cinnamic and aliphatic trithio! ortho!esters ð61JOC1646Ł[ However\ the reaction may not be general for the preparation of aliphatic trithio!ortho!esters*trithioacetates and trithiopropionates could not be prepared from the cor! responding dithioacetals using sodium amide and dialkyl disul_des\ presumably because of com! peting elimination reactions ð51RTC0998Ł[ The preparation of trithio!ortho!formate esters by this method appears to be dependent on the nature of the substituents on sulfur\ and on the base used[ Seebach et al[ prepared the mixed trithio!ortho!formate ester "77# in 84) yield from bis"ben! zenethio#methane using n!butyllithium and dimethyl disul_de "Equation "47## ð61CB2179Ł\ whereas Frohling and Arens obtained only tetraethyl tetrathio!ortho!carbonate from the reaction of the bis"ethanethio#methane with sodium amide and diethyl disul_de "Scheme 06# ð51RTC0998Ł[ Doubly 02 C!labelled trimethyl trithio!ortho!formate has been prepared by a related method\ in which the lithiated dithioacetal "78# is treated sequentially with elemental sulfur followed by 02C!labelled methyl iodide "Scheme 07# ð73HCA0969Ł[ SR2
SR2
M+B–
R1
R1
–
SR2
R3SSR3
M+
SR2 SR2 SR3
R1
SR2 (85) Scheme 16
SEt
i, NaNH2
Ph
Ph ii, EtSSEt 76%
SEt
MeS
S
SEt SEt SEt
(57)
S
Ph
Ph S
S
(86)
(87)
SPh
SPh
i, BunLi
(58)
MeS SPh
SEt
NaNH2, EtSSEt
ii, MeSSMe 95%
SEt EtS
SEt
SPh (88)
NaNH2, EtSSEt
EtS
SEt
SEt SEt SEt
Scheme 17
SMe Li+
–
i, BunLi
H
*
SMe (89)
ii, 1/8 S8
*
SMe SMe S– Li+
Scheme 18
Me*I
H 58%
*
SMe SMe * SMe
76
Three Sulfurs
Trithio!ortho!formates have been prepared by reaction of N!p!toluenesulfonylsul_limines "89# derived from dithioacetals of formaldehyde with alkanethiols and arenethiols under alkaline con! ditions "Equation "48## ð65S440Ł[ Mixed trithio!ortho!esters are available by this method[ SR1
SR2
R3SH, KOH
R2
S
(59)
R1S
61–82%
SR3
TosN (90)
5[92[2[0[5 Trithio!ortho!formates from trithiocarbonates Addition of phenyllithium to diphenyl trithiocarbonate at −67>C yields the triphenyl! thiomethylide anion "80^ Equation "59##[ This anion\ when prepared by a di}erent method\ has been quenched with deuterated water to give the deuterated triphenyl trithio!ortho!formate "81# ð61CB376Ł[ Similar addition of methyllithium to the dithiolone "82#\ followed by quenching with acetic acid\ yielded the 1!methanethio!0\2!dithiole "83^ Scheme 08# ð76TL3042Ł[ The use of lithiated trithio!ortho!formates for the preparation of higher trithio!ortho!esters is discussed in Section 5[92[2[1[0[ PhS
PhSLi, THF, –78 °C
Li+
S PhS
D
S
S
MeLi, THF, –60 °C
S
S –
S
(60)
SPh SPh SPh (92)
S S
SPh SPh SPh (91) –
S
S
AcOH
SMe Li+
S
S
S
S
SMe 75%
(93)
(94) Scheme 19
Diphenyl trithiocarbonate undergoes cycloaddition reactions with diaryldiazomethanes to pro! duce the cyclic trithio!ortho!ester derivatives "84^ Equation "50## ð54CB2292Ł[ PhS
Ar2CN2
S PhS
S Ar
SPh Ar
(61)
SPh (95)
5[92[2[0[6 Trithio!ortho!formates from tetrathio!ortho!carbonates Seebach ð56AG"E#331Ł reported the preparation of the trithio!ortho!formate "86# by treatment of the tetrathio!ortho!carbonate "85# with n!butyllithium at −67>C\ followed by quenching the reaction with water "Scheme 19#[ The reaction proceeds via the lithiated trithio!ortho!formate ester "87#[ Similar treatment of tetraphenyl tetrathio!ortho!carbonate with n!butyllithium gave the tri!
77
Three Chalco`ens
phenylthiomethylide anion "80#\ which has been used to prepare the deuterated trithio!ortho!formate "81# ð61CB376Ł[ The use of lithiated trithio!ortho!formates for the preparation of higher trithio! ortho!esters is discussed in Section 5[92[2[1[0[ S S
SMe
S
BunLi, THF, –78 °C
–
SMe
(96)
SMe 70%
Li+
S
S
H2O
SMe
S
(98) Scheme 20
(97)
5[92[2[1 Preparation of Trithio!ortho!esters from other Trithio!ortho!esters 5[92[2[1[0 Higher trithio!ortho!esters from trithioformate esters In 0851\ Hine et al[ ð51JA0640Ł reported the generation of the potassium trithio!ortho!formate salt "88# by deprotonation of trimethyl trithio!ortho!formate with potassium amide\ and the reaction of this with methyl iodide to produce trimethyl trithio!ortho!acetate in 64) yield "Scheme 10#[ Seebach et al[ ð56AG"E#331\ 61CB376\ 61CB2179Ł later described the generation of several lithiated trithio!ortho! formate esters from the appropriate trithio!ortho!formate with n!butyllithium at −67>C\ and the subsequent reactions of these with a range of electrophiles to yield higher trithio!ortho!esters[ This has since developed into a general method for the homologation of trithio!ortho!formates[ Thus\ lithiated trithio!ortho!formates react with alkyl halides to give aliphatic trithio!ortho!esters ð56AG"E#331\ 61CB376\ 61CB2179\ 65CL32\ 71TL2396Ł\ with aldehydes and ketones to give a!hydroxy! trithio!ortho!esters ð56AG"E#331\ 61CB376\ 65CL32\ 70TL3998Ł\ with epoxides to give b!hydroxy trithio! ortho!esters ð56AG"E#331\ 61CB376Ł\ with cyclic a\b!unsaturated ketones to give g!ketotrithio!ortho! esters ð64CC105\ 78TL4370Ł\ with carbon dioxide to give trithiomono!ortho!oxalates ð56M0932Ł\ with carbon disul_de to give trithiomono!ortho!dithiooxalates ð77T1952Ł\ with chloroformate esters to give trithiomono!ortho!oxalate esters ð56AG"E#331\ 61CB376Ł and with iodine to give coupled hexa! thiodi!ortho!oxalates ð61CB2781Ł "Scheme 11#[ An example of the acylation of a lithiated trithio! ortho!formate by reaction with a lactone has been reported "Equation "51##\ but this reaction is not general ð80CJC304Ł[ Since lithiated trithio!ortho!esters may also be obtained from trithiocarbonates "Section 5[92[2[0[5# and tetrathio!ortho!carbonates "Section 5[92[2[0[6#\ these compounds should also be regarded as precursors of higher trithio!ortho!esters[ SMe MeS
KNH2, NH3
SMe
MeI
SMe
75%
–
K+ MeS
SMe
SMe SMe SMe
(99) Scheme 21
S
S Li+
MeS
O
–
O
S
OH O
(62)
S SMe
Triethyl trithio!ortho!heptanoate has been prepared by a radical homologation procedure\ involv! ing treatment of triethyl trithio!ortho!formate with 0!hexene in the presence of t!butyl hydroperoxide "Equation "52## ð77MI 592!90Ł[ SEt
1-hexene, ButO2H, 130 °C
SEt
76%
EtS
SEt SEt
(63)
SEt
5[92[2[1[1 Trans!esteri_cation of trithio!ortho!esters In contrast to the chemistry of ortho!esters\ relatively little work has been published on the preparation of trithio!ortho!esters by trans!esteri_cation reactions of other trithio!ortho!esters with
78
Three Sulfurs SR1 SR2 SR3
R4
SR1 SR2 SR3
HO R4 R5
OH SR1 SR2 SR3
R4
R4X
O
R4COR5
O
R4 O
SR2 R1S
BunLi, THF, –78 °C
Li+ –
SR3
SR1 SR2 SR3
SR1 SR2 SR3
CO2
O CS2
HO
R4OCOCl
SR1 SR2 SR3
I2
SR1 SR2 SR3
S R1S 2 RS R 3S
SR1 SR2 SR3
SR1 SR2 SR3
O R4O
HS
Scheme 22
thiols[ Mixed trithio!ortho!esters undergo rapid acid catalysed disproportionation reactions to yield mixtures of trithio!ortho!esters "Scheme 12# ð50LA"537#10Ł[ The dithiolane "099# and dithiane "090# have been prepared by heating triethyl trithio!ortho!formate with the appropriate dithiol in the presence of zinc chloride ð77URP0310633Ł[ R1
SR2 SR3 SR3
H+
R1
SR2 SR2 + SR2 Scheme 23
R1
SR2 SR2 SR3
+
R1
SR3 SR3 SR3
S
S
SEt
SEt S (100)
S (101)
5[92[2[1[2 Modi_cation of R0 and R1 of R0C"SR1#2 Treatment of triaryl trithio!ortho!acetates with deuterated tri~uoroacetic acid in deutero! chloroform results in a rapid proton exchange reaction to give the deuterated trithio!ortho!acetates "091^ Equation "53## ð64JOC852Ł[ However\ attempts to homologate triaryl trithio!ortho!acetates by reaction with electrophilic acylating agents have not been successful ð64JOC852Ł[ SAr SAr SAr
CF3CO2D, CDCl3, RT, 5 min
D3C ca. 100%
SAr SAr SAr (102)
(64)
Deacetylation of tris"acetylthio#methane using methanolic hydrogen chloride produced meth! anetrithiol "092^ Equation "54## in 49) yield ð65CS011Ł[ This product is stable at −29>C\ although
89
Three Chalco`ens
it polymerises slowly at 19>C[ The hydrolysis proceeds via di! and monoacetyl trithiomethane intermediates\ which can be detected in the 0H NMR spectrum of the reaction mixture[ SAc
SH
2% HCl in MeOH, 6 h
AcS
(65)
HS SAc
50%
SH (103)
5[92[2[2 Methods for the Preparation of Oxidised Derivatives of Trithio!ortho!esters 5[92[2[2[0 Oxidised trithio!ortho!esters containing at least one sulfoxide group Triaryl trithio!ortho!formate esters are oxidised to the triaryl sulfoxide derivatives in high yields on treatment with peroxyacetic acid "Equation "55## ð53CR"148#3940Ł[ The sulfoxide "093# has been prepared by oxidation of the corresponding sul_de with peroxybenzoic acid "Equation "56## ð37RTC773Ł[ SAr
SOAr
MeCO3H, Et2O
ArS
(66)
ArOS SAr
SO2Me MeS
>90%
PhCO3H
SOAr
SO2Me (67)
MeOS
SO2Me
SO2Me (104)
5[92[2[2[1 Oxidised trithio!ortho!esters containing at least one sulfone group Treatment of the sulfone "094# with two equivalents of N!ethanethiophthalimide in the presence of potassium t!butoxide produced the sulfonyldithio!ortho!ester derivative "095# in high yield "Equa! tion "57## ð71CC0072Ł[ Bis"sulfonyl#methanes "096# react with alkyl thioalkyl sulfones and alkane! sulfonyl or arenesulfonyl chlorides in the presence of sodium ethoxide to give disulfonylthiomethanes "097# ð22JCS295Ł and trisulfonylmethanes "098# ð30CB0556Ł respectively "Scheme 13#[ These oxidised trithio!ortho!formate derivatives produce the analogous trithio!ortho!acetate derivatives on treat! ment with methyl iodide in aqueous alkali "Equation "58## ð0781CB236\ 0781CB250Ł[ O 2 equiv.
O Ph
N SEt, KOBut, DMSO O
SO2Me
O Ph
87%
(105)
SO2R1 R3S
R3SSO2R4, NaOEt, EtOH
SO2R2 (108)
SO2R1
R3SO2Cl, NaOEt, EtOH
SO2R2 (107) Scheme 24
SO2R2 R1SO2 SOnR3
MeI, aq. NaOH
SO2Me SEt SEt (106)
(68)
SO2R2 R1SO
2
SO2R3 (109)
SO2R1 SO2R2 SOnR3
(69)
80
Three Seleniums
Trisulfones "009# are the products normally obtained from the oxidation of trialkyl and triaryl trithio!ortho!formates using acidic permanganate ð0781CB236\ 22RTC326Ł\ though Laves ð0789CB0303Ł has reported that controlled oxidation of triphenyl trithio!ortho!formate using this reagent produces the disulfone "000#[ Yields from these permanganate oxidations are often low due to the competing formation of disulfonylmethanes and sulfonic acids ð96CB0639\ 22RTC326Ł[ Trialkyl trisulfones have been obtained from the oxidation of trialkyl trithio!ortho!formates with peroxyacetic and mon! operoxyphthalic acids ð35RTC42\ 42LA"470#022\ 56USP2222996Ł[ The tricyclic trisulfones "001\ R H\ Me# and triaryl sulfones "002# were prepared by oxidation of the corresponding trithio!ortho!esters using hydrogen peroxide in acetic acid ð44JA498\ 53CR"148#3940Ł[ Oxidation of disulfones "003\ R H\ Me# with alkaline permanganate or hydrogen peroxide produced the corresponding trisulfones in high yields "Equation "69## ð0781CB236\ 20JCS1526\ 35RTC42Ł[ SO2
SO2Ph
SO2R
R
PhS
RO2S
SO2Ph (111)
SO2R (110)
R1
SO2R2 SO2R2 SR3 (114)
SO2Ar ArO2S
SO2 SO2 (112)
KMnO4 / HO– or H2O2
SO2Ar (113)
SO2R2 SO2R2 SO2R3
R1
(70)
The disulfonylthiomethane "005# was obtained in 83) yield from the sodium ethanethiolate reduction of the disulfonyldithiomethane "004^ Equation "60## ð71CC0072Ł[ EtS
SO2Et SO2Et SEt (115)
NaSEt, THF 94%
SO2Et (71)
EtS SO2Et (116)
5[92[2[2[2 Oxidised trithio!ortho!esters containing at least one sulfonate group Methanetrisulfonic acid "006# has been prepared by various methods\ including sulfonation of methanedisulfonic acid and oxidation of thiol methanetrisulfonic acid^ these have been reviewed by Backer ð29RTC0096Ł and summarised by DeWolfe ðB!69MI 592!90Ł[ The trimethyl and triethyl esters "008\ R Me\ Et# were obtained by treatment of the silver"I# salt "007# with methyl iodide and ethyl iodide respectively "Equation "61## ð38AK"0#120\ 49ACS286Ł[ SO3H HO3S SO3H (117)
SO3– –O S 3
3Ag+ SO3–
(118)
RI, C6H6
SO3R (72)
RO3S SO3R (119)
5[92[3 FUNCTIONS BEARING THREE SELENIUM ATOMS Triseleno!ortho!esters contain a carbon atom bearing three alkaneseleno or areneseleno groups[ Methods for the preparation of triseleno!ortho!esters have been reviewed brie~y by Krief and Hevesi ð73MI 592!90Ł[
81
Three Chalco`ens
5[92[3[0 Methods for the Preparation of Triseleno!ortho!esters 5[92[3[0[0 Triseleno!ortho!esters from RC"X0#"X1#X2 "i# From 0\0\0!trihaloalkanes Triseleno!ortho!formates "019\ R Me\ Ph# have been obtained from the treatment of bromoform with the appropriate sodium selenolate "Equation "62## ð73HCA0969\ 73S328Ł[ The sodium selenolates were prepared by reduction of diselenides in situ^ sodium methaneselenolate was prepared by the sodium:liquid ammonia reduction of dimethyl diselenide ð73HCA0969Ł\ and sodium benzene! selenolate was prepared by reduction of diphenyl diselenide using hydrazine ð73S328Ł[ Seebach ð73HCA0969Ł prepared 02C!labelled trimethyl triseleno!ortho!formate from 02C!labelled bromoform using this method[ CHBr3
NaSeR
SeR (73)
RSe SeR (120)
"ii# From a\a!dihalo ethers A range of alkane! and areneselenolates were shown to undergo a zinc promoted reaction with dichloromethyl methyl ether to give trialkyl and triaryl triseleno!ortho!formate esters in yields of 39Ð35) "Equation "63## ð60ZOR362Ł[ Cl OMe
RSeH, Zn, Et2O
SeR (74)
RSe
40–46%
Cl
SeR
"iii# From ortho!esters Trans!esteri_cation of ortho!formate esters with methane! or benzeneselenol in the presence of boron tri~uoride etherate produced the triseleno!ortho!formates "010\ R1 Me# and "010\ R1 Ph# in yields of 70) and 53) respectively "Equation "64## ð73JA2673\ 61CB400Ł[ Trimethyl ortho!acetate and methaneselenol gave trimethyl triseleno!ortho!acetate in 55) yield under these conditions ð68JOM"0660#Ł[ Ortho!esters have also been shown to undergo exchange reactions with boron tri! selenides to give triseleno!ortho!esters "Equation "65##\ though these reactions are subject to steric limitations[ Thus\ boron tris"benzeneselenide# and triethyl ortho!formate gave triphenyl triseleno! ortho!formate in 65) yield\ boron tris"methaneselenide# and trimethyl ortho!acetate produced trimethyl triseleno!ortho!acetate in 28) yield\ whereas the reaction between boron tris! "benzeneselenide# and trimethyl ortho!acetate proceeded only very slowly\ a}ording little of the triseleno!ortho!ester product ð68JOC0772\ 68JOC3168Ł[ R1O OR1
R2SeH, BF3•OEt2
SeR2 (75)
R2Se
R 1O
SeR2 (121)
R1
OR2 OR2 OR2
B(SeR3)3, cat. TFA, CHCl3
R1
SeR3 SeR3 SeR3
(76)
5[92[3[0[1 Triseleno!ortho!esters from carboxylic acids 02
C!Labelled triphenyl triseleno!ortho!formate has been prepared in 37) yield by the acid catalysed reaction of 02C!labelled formic acid with benzeneselenol "Equation "66## ð73HCA0969Ł[
82
Three Seleniums
The preparation of triseleno!ortho!esters from other carboxylic acid derivatives has not been reported[ PhSeH, HCl, 0 °C, 1 h
HC*O2H
(77)
HC*(SePh)3
then RT, 30 d 48%
5[92[3[0[2 Triseleno!ortho!esters from triselenocarbenium salts In a manner analogous to the reduction of trithiocarbenium salts discussed in Section 5[92[2[0[3\ 1!alkaneseleno!0\2!diselenoles may be prepared by sodium borohydride reduction of the cor! responding triselenocarbenium salts[ 1!Methaneseleno!0\2!diselenole "011\ R Me# was prepared from the corresponding triselenocarbenium iodide in a yield of greater than 79) using this method "Equation "67## ð64TL0148Ł\ and the 1!ethaneseleno derivative "011\ R Et# was similarly prepared from the analogous tetra~uoroborate salt ð75ZC027Ł[ Se +
Se
NaBH4
SeR X–
Se (78)
SeR Se (122)
5[92[3[0[3 Triseleno!ortho!esters from diselenoacetals and related compounds A few derivatives of triseleno!ortho!esters have been prepared by the direct electrophilic selenation of diselenoacetals and related compounds[ Reaction of a\a!bis"benzeneseleno#acetaldehyde with morpholinobenzeneselenamide produced the triseleno!ortho!ester "012^ Equation "68## ð71TL0446\ 74BSF0108Ł\ and reaction of the selenated enamine "013# with the same reagent gave the addition product "014# ð74BSF0108Ł[ Treatment of acetone with red selenium under basic conditions produced the cyclic selenium salt "015# ð81CC0428Ł[ This reaction proceeds through the diselenoacetal!like intermediates "016# and "017#\ and involves three electrophilic a!selenation steps "Scheme 14#^ it is therefore a counterpart of the haloform reaction[ PhSeN
PhSe CHO PhSe
O
PhSe PhSe CHO PhSe (123)
(79)
O PhSe PhSe PhSe
PhSe PhSe
N
N N O
O (124)
(125)
5[92[3[0[4 Triseleno!ortho!formates from tetraseleno!ortho!carbonates Seebach ð58AG"E#349Ł showed that the lithium triselenomethylide "018# is generated by treatment of tetraphenyl tetraseleno!ortho!carbonate with n!butyllithium at −67>C "Equation "79##\ and that this reacts with deuterated water to give the deuterated triseleno!ortho!formate "029#[ The use of lithiated triseleno!ortho!formates\ for example "018#\ for the preparation of higher triseleno!ortho! esters is discussed in the next section[
83
Three Chalco`ens O O
Se– Se
Red Se, K2CO3, (Ph3P)2NCl, RT, 16 h 26%
Se
Se (126)
Se Se
O
O O
Se
Sex Sex Se
Sey (127) Scheme 25
PhSe
N+(PPh3)2
SePh SePh SePh
BunLi, THF, –78 °C
Se (128)
Li+
–
Se Se
SePh SePh SePh
(80)
(129)
D
SePh SePh SePh (130)
5[92[3[0[5 Higher triseleno!ortho!esters from triseleno!ortho!formate esters Metallated triseleno!ortho!formates "020# are generated on treatment of triseleno!ortho!formate esters with strong bases^ the lithiated triseleno!ortho!formate "020\ R Ph# is obtained from tri! phenyl triseleno!ortho!formate and lithium di!s!butylamide at −67>C ð58AG"E#349Ł\ and "020\ R Me# is generated from trimethyl triseleno!ortho!formate and n!butyllithium at −67>C ð68JOM"0660#Ł[ These lithiated triseleno!ortho!formates react with a range of electrophiles to yield higher triseleno!ortho!esters[ Thus\ lithiated triseleno!ortho!formates react with] alkyl halides to give aliphatic triseleno!ortho!esters ð58AG"E#349\ 68JOM"066#0\ 71TL2396Ł^ aldehydes to give a!hyd! roxytriseleno!ortho!esters ð58AG"E#349\ 70TL3998Ł\ and epoxides to give b!hydroxytriseleno!ortho! esters ð67TL2860Ł "Scheme 15#[ Tris"tri~uoromethyl# triseleno!ortho!formate yielded the cor! responding triseleno!ortho!acetate "021# on metallation with potassium di!i!propylamide\ followed by treatment with methyl iodide "Equation "70## ð73T3852Ł[ Since metallated triseleno!ortho!formates may also be obtained from tetraseleno!ortho!carbonates "Section 5[92[3[0[4#\ these should also be regarded as precursors of higher triseleno!ortho!esters[ SeR1 SeR1 SeR1
R2 R2X
SeR1 R1Se SeR1
Li+ –B, THF, –78 °C
Li+
–
SeR1 SeR1 SeR1
(131)
R2CHO
SeR1 SeR1
R2
SeR1
O
OH
R2
SeR1
R2 OH Scheme 26
SeR1 SeR1
84
Mixed Includin` Oxy`en SeCF3
SeCF3 SeCF3 SeCF3 (132)
i, K+ –N(Pri)2
F3CSe
ii, MeI
SeCF3
(81)
5[92[4 MIXED CHALCOGEN FUNCTIONS INCLUDING OXYGEN Mono! and dithio!ortho!esters are derivatives of carboxylic ortho!esters in which one and two of the oxygen substituents respectively are replaced with sulfur substituents[ Similarly\ mono! and diseleno!ortho!esters are mixed oxygen and selenium functions containing one and two selenium substituents respectively[ Monoselenomonothio!ortho!esters bear one oxygen\ one sulfur and one selenium substituent[ Oxidised derivatives of several mixed functions containing sulfur are known[ Methods for the preparation of mixed oxygen and sulfur functions have been reviewed by Simchen ð74HOU"E4#2Ł[
5[92[4[0 Methods for the Preparation of Functions R0C"OR1#"OR2#SR3 5[92[4[0[0 From R0C"X0#"X1#X2 Triphenyl monothio!ortho!formate has been prepared in 31) yield by reaction of chloro! diphenoxymethane with benzenethiol in the presence of pyridine "Equation "71## ð51CB0748Ł[ OPh
PhSH, pyridine
Cl
OPh
42%
OPh
(82)
PhS OPh
Monothio!ortho!esters have been prepared from the reactions of ortho!ester derivatives with thiols[ Ortho!esters react with one equivalent of n!butanethiol in the presence of aluminum tri! chloride to give monothio!ortho!esters "Equation "72##^ yields are reasonable "54Ð79)# for mono! thio!ortho!formates and !acetates\ but are lower "ca[ 24)# for thio!ortho!benzoates ð57CR"C#0495Ł[ This reaction will also proceed in the absence of a catalyst^ monothio!ortho!formates are obtained in high yields ð58BSF214Ł\ though yields are low for monothio!ortho!acetates and !ortho!benzoates\ which are obtained as mixtures with dithio!ortho!esters ð69MI 592!91Ł[ Treatment of the O!acyl ortho! formate ester "35# with a range of thiols in the presence of triethylamine produced the monothio! ortho!esters "022# in yields of 34Ð64) "Equation "73## ð58RTC786Ł[ The acid catalysed trans!esteri! _cation of ortho!esters with 1!hydroxybenzenethiol produced the cyclic monothio!ortho!esters "023# in good yields "69Ð66)# "Equation "74## ð64S559Ł[ Cyclic monothio!ortho!ester derivatives have also been obtained from the exchange reactions of ortho!esters with 1!hydroxyethanethiol ð66MI 592!90Ł and 1!thiohydroxyacetic acid ð67IZV357Ł[ OR2 OR2 OR2
R1
OEt AcO
1 equiv. BunSH, AlCl3, heat
RSH, Et3N, RT, 20 min 45–75%
OEt (46)
OR2 SBu OR2
R1
(83)
OEt (84)
RS OEt (133)
SH
R1
OR2 OR2 OR2
OH ,H2SO4, 100 °C, 15 min 70–77%
S
OR2 (85)
O (134)
R1
85
Three Chalco`ens
5[92[4[0[1 From monothiocarboxylic esters Monothio!ortho!benzoate esters have been prepared in yields of 55) or more by reaction of a monothiobenzoate ester with a sodium alkoxide\ followed by alkylation of the thiolate intermediate with an alkyl iodide "Scheme 16# ð78S573Ł[ However\ this procedure is not suitable for the preparation of monothio!ortho!esters from simple aliphatic monothio esters\ which may undergo deprotonation under the reaction conditions ð78S573Ł[ Treatment of the hydroxy monothioesters "024\ n 9\ 0# with sodium hydride gave the cyclic thiolate intermediates "025\ n 9\ 0#\ which were methylated in situ to yield monothio!ortho!esters "026\ n 9\ 0# in overall yields of 24Ð67) "Scheme 17# ð75JA5572Ł[ Unlike the reaction of simple monothio!ortho!esters with alkoxides\ this procedure is applicable to the preparation of cyclic monothio!ortho!acetate esters as well as monothio!ortho! benzoates[ S Ar
NaOR1, R1OH or THF
S– OR1 OR1
Ar
OR1
R 2I
Ar
SR2 OR1 OR1
Scheme 27
S
O
S–
NaH, MeCN, 0 °C
R
( )n
( )n O
R
OH
(135)
Me3O+BF4– or MeI 35–78%
O
(136) Scheme 28
MeS
O
R
O
( )n (137)
5[92[4[0[2 From dioxo! and oxothiocarbenium salts Monothio!ortho!esters are obtained from the treatment of dioxocarbenium salts with thiols[ This reaction is analogous to the preparation of ortho!esters from dioxocarbenium salts and alcohols described in Section 5[92[1[0[3[ Reaction of the dimethyl dioxocarbenium salt "027# with meth! anethiol in the presence of triethylamine produced the monothio!ortho!ester "028^ Equation "75## ð76JOC1546Ł\ and the cyclic dioxocarbenium tetra~uoroborate salts "039\ R Me\ Ph^ n 9\ 0# gave monothio!ortho!esters "030\ R Me\ Ph^ n 9\ 0# on treatment with lithium methanethiolate "Equation "76## ð75JA5572Ł[ Alternatively\ the salts "039# could be converted to monothio!ortho! esters "030# by treatment with sodium sul_de\ followed by methylation of the thiolate intermediate with trimethyloxonium tetra~uoroborate or methyl iodide ð75JA5572Ł[ The stable monothio!ortho! hydrogen ester "032# was obtained by treatment of the bicyclic dioxocarbenium tetra~uoroborate "031# with sodium hydrosul_de "Equation "77## ð79JA6468Ł[ OMe MeO
BF4–
+
MeSH, Et3N
SMe OMe OMe
MeO
OMe (138)
(139) O
R
(86)
( )n
+
BF4–
LiSMe
MeS
( )n R
O (140)
O
NaSH
O
+
BF4– (142)
O
(87)
O (141)
(88) O
SH
O
(143)
Monothio!ortho!esters may also be prepared from oxothiocarbenium salts by addition of alk! oxides[ Reaction of 1!ethoxythiolenium tetra~uoroborate with sodium ethoxide gave 1\1!diethoxy!
86
Mixed Includin` Oxy`en
thiolane "Equation "78## ð45CB1959Ł\ and the 1!alkyl! and 1!aryl!1!alkoxy!0\2!benzoxathioles "034# were prepared by treatment of the oxathiolium salts "033# with alcohols in the presence of sodium hydrogen carbonate "Equation "89## ð68S112Ł[ OEt
NaOEt +
S
OEt
S
(89)
OEt
BF4–
S +
O (144)
S
R2OH, NaHCO3, MeCN, 0–5 °C, 10 min
R1 BF4–
R1 (90)
78–97%
O (145)
OR2
5[92[4[0[3 From monothioacetals and related compounds The cyclic monothio!ortho!formate "036# has been prepared in 23) yield by methanolysis of the N!p!toluenesulfonylsul_limine "035^ Equation "80## ð74JOC546Ł[ The alkaline reaction conditions help prevent the product from undergoing disproportionation reactions[ This procedure is analogous to the preparation of trithio!ortho!esters discussed in Section 5[92[2[0[4[ NTos S
S
MeOH, KOH
(91)
OMe 34%
O (146)
O (147)
5[92[4[0[4 From 1!alkoxythiophenes Terrier et al[ demonstrated that the highly electron de_cient 1\3!dinitro!4!methoxythiophene undergoes addition of methanol on treatment with potassium methoxide to produce the stable salt "037#\ which was isolated as a purple solid in virtually quantitative yield "Equation "81## ð64JOC1800Ł[ NO2
NO2 KOMe, MeOH, RT, 15 min
O2N
S
ca. 100%
OMe
–
O2N
S
(92)
OMe K+ OMe
(148)
5[92[4[1 Methods for the Preparation of Functions R0C"OR1#"SR2#SR3 5[92[4[1[0 From R0C"X0#"X1#X2 Cyclic dithio!ortho!esters have been obtained from the reactions of a\a!dichloro ethers with dithiolates[ Treatment of dichloromethyl methyl ether with disodium ethane!0\1!dithiolate "gen! erated from ethanedithiol and sodium# gave 1!methoxy!0\2!dithiolane in 57) yield\ and dilithium propane!0\2!dithiolate "generated from propane!0\2!dithiol and n!butyllithium# reacted with di! chloromethyl methyl ether to produce 1!methoxy!0\2!dithiane in 34) yield "Scheme 18# ð61HCA64Ł[
S
HS(CH2)2SH, Na, MeCN
OMe S
Cl OMe
68%
Cl Scheme 29
HS(CH2)3SH, BunLi, THF
S
45%
S
OMe
87
Three Chalco`ens
Dithio!ortho!esters have also been obtained from exchange reactions of ortho!esters with n! butanethiol ð58BSF214Ł\ though these are normally isolated as side!products from the preparation of monothio!ortho!esters by this method "see Section 5[92[4[0[0# ð69MI 592!91Ł[
5[92[4[1[1 From dithiocarbenium salts Okuyama et al[ ð76JOC1546Ł prepared the dithio!ortho!ester "049# by addition of sodium methoxide to the dithiocarbenium perchlorate "038^ Equation "82##[ This procedure is analogous to the prep! aration of trithio!ortho!esters by the addition of thiols to dithiocarbenium salts discussed in Section 5[92[2[0[3[ SMe ClO4– SMe
MeO
NaOMe, MeOH, MeCN
SMe SMe OMe
MeO
+
(149)
(93)
(150)
5[92[4[1[2 From mono! and dithioacetals and related compounds Dithio!ortho!ester derivatives may be prepared by the reaction of metallated monothioacetals with disul_des[ Deprotonation of 0\2!oxathiane by treatment with n!butyllithium at −67>C\ followed by reaction with dimethyl disul_de produced 1!methanethio!0\2!oxathiane in 71) yield "Scheme 29# ð70TL1994\ 74JOC546Ł[ In a similar manner\ lithiation of a series of sulfonyl oxiranes "040# followed by treatment with diphenyl disul_de gave the oxidised dithio!ortho!ester derivatives "041# in yields of 34Ð89) "Scheme 20# ð80JCS"P0#2980Ł[ S
S
i, BunLi, THF, –100 °C
ii, MeSSMe
S
82%
O
Li+
–
SMe
O
O
Scheme 30
O
R1
SO2Ph
i, BunLi, THF, –100 °C
O
R1
SO2Ph –
R2
R2
ii, PhSSPh
O
R1
Li+
SO2Ph R2
(151)
SPh (152)
Scheme 31
Lithiation of the unsaturated dithioacetal "042# followed by reaction with benzophenone produced the bicyclic dithio!ortho!ester "043# in 87) yield "Scheme 21# ð58S06Ł[ This reaction proceeds via cyclisation of the intermediate ketene dithioacetal "044#[ Selenocyclisation of the related hydroxy ketenedithioacetal "045# gave the spirobicyclic dithio!ortho!ester "046^ Equation "83## ð79JOC1125Ł[
S S
S
i, BunLi
S S
ii, Ph2CO
98%
Li+ –O
Ph
S
Ph
Ph (153)
(155) Scheme 32
Ph
O
(154)
88
Mixed Includin` Oxy`en S
SePh PhSeCl, Et3N, THF, –78 °C
S HO
S
64%
S
Ph (156)
(94) O
Ph
(157)
Some dithioacetals undergo direct oxygenation on treatment with organic peroxides[ Reaction of trithiane with t!butyl peroxybenzoate in the presence of copper"I# chloride gave the benz! oyloxytrithiane "53# and dibenzoyloxytrithiane "047^ Equation "84##^ the yield of "53# was at an optimum "69Ð79) based on recovered trithiane# when 9[6 equivalents of t!butyl peroxybenzoate were used\ and "047# was obtained as the major product when 2[9 equivalents of t!butyl per! oxybenzoate were used ð63BCJ0385Ł[ 1!Benzoyloxydithiane has been generated by an analogous method\ though this product was too unstable to isolate and characterise ð63BCJ0385Ł[ S S
S
S
PhCO3But, CuCl, C6H6, heat
S
S
+
OCOPh
OCOPh
S S
S
(95)
PhOCO (64)
(158)
Cyclic dithio!ortho!formates have been prepared by reaction of N!p!toluenesulfonylsul_limines "89# derived from dithioacetals of formaldehyde with alcohols under alkaline conditions "Equation "85## ð65S440Ł[ SR1
SR1
R3OH, KOH
(96)
R 3O
SR2
56–93%
SR2
TosN (90)
5[92[4[1[3 Miscellaneous methods Generation of benzyne in the presence of carbon disul_de and methanol gave 1!methoxy!0\2! benzodithiole in 67) yield "Scheme 22# ð63CC055Ł[ The reaction proceeds via addition of methanol to the carbene "048#\ which is formed by the cycloaddition of carbon disul_de to benzyne[ A modi_cation of this reaction involves the generation of benzyne by diazotisation of anthranilic acid using an alkyl nitrite^ in this case\ the alkoxy group of the alkyl nitrite is the source of the 1! substituent of the product benzodithiole "Equation "86## ð64S27Ł[ N N
Pb(OAc)4
S
CS2
MeOH
: S
N NH2
S OMe S
(159) Scheme 33
CO2H
RONO, CS2
NH2
S OR
(97)
S
A series of cyclic oxidised derivatives of dithio!ortho!esters "050# has been prepared by the lithium t!butyl peroxide oxidation of alkenes "059^ "Equation "87## ð80JCS"P0#2980Ł[ SO2Ar R1
SR2 (160)
O
LiO2But, THF, –78 °C to –18 °C
SO2Ar R1
SR2 (161)
(98)
099
Three Chalco`ens
5[92[4[2 Methods for the Preparation of Functions R0C"OR1#"OR2#SeR3 5[92[4[2[0 From 1!alkoxyselenophenes In an analogous reaction to that described in Section 5[92[4[0[4\ addition of potassium methoxide to 1\3!dinitro!4!methoxyselenophene produced the stable salt "051#\ which was isolated as a purple solid in virtually quantitative yield "Equation "88## ð64JOC1800Ł[ NO2
NO2 KOMe, MeOH, RT, 15 min
O2N
OMe
Se
–
ca. 100%
O2N
OMe K+
(99)
Se OMe (162)
5[92[4[3 Methods for the Preparation of Functions R0C"OR1#"SeR2#SeR3 5[92[4[3[0 From R0C"X0#"X1#X2 Dihalomethyl methyl ethers react with selenolates to give diseleno!ortho!esters[ Treatment of dichloromethyl methyl ether with sodium benzeneselenolate "generated by the sodium borohydride reduction of diphenyl diselenide# gave the diseleno!ortho!formate ester "052# in 67) yield "Equation "099## ð68JA5527Ł[ Other dichloromethyl alkyl and aryl ethers gave diseleno!ortho!formates "053\ R alkyl\ aryl# in yields of 31Ð65) on treatment with sodium areneselenolates "generated from the selenophenol and metallic sodium# "Equation "090## ð75ZOR096Ł[ Dichloromethyl ethers also react with areneselenomagnesium halides to give diseleno!ortho!formates\ though yields are usually lower than those obtained from reaction with the corresponding sodium selenolates ð75ZOR096Ł[ Reaction of dibromomethyl methyl ether with dilithium benzene!0\1!diselenolate gave 1!methoxy!0\2!di! selenole in 27) yield "Scheme 23# ð77HCA0131Ł[ Cl
NaSePh
OMe 78%
Cl
Cl
PhSe
2 Se, THF/Et2O, –60 °C
Se– Li+
(101)
OR PhSe (164)
42–76%
Cl
(100)
OMe PhSe (163)
ArSeH/Na, MeO(CH2)2OMe
OR
Li
PhSe
Br2CHOMe
Se
38%
Se
OMe Se– Li+ Scheme 34
Li
The cyclic diseleno!ortho!esters "055\ R H\ Me# have been generated from the boron tri~uoride etherate catalysed exchange reactions between triethyl ortho!formate and the 0\2!diselenolates "054\ R H\ Me^ "Equation "091##[ However\ these products were not isolated and characterised\ but were used in situ for the preparation of diselenothio!ortho!esters "see Section 5[92[5[1[0# ð78H"17#278Ł[ Se– Li+
Se
HC(OEt)3, BF3•OEt2
OEt R
Se–
Li+
(165)
R
(102)
Se (166)
5[92[4[4 Methods for the Preparation of Functions R0C"OR1#"SR2#SeR3 5[92[4[4[0 From monothioacetals and related compounds Monoselenomonothio!ortho!ester derivatives have been prepared from the reactions of lithiated monothioacetals with diselenides[ Lithiation of 0\2!oxathiane with n!butyllithium followed by reac!
090
Mixed Sulfur And Selenium
tion with dimethyl diselenide produced 1!methaneseleno!0\2!oxathiane in 49) yield "Scheme 24# ð70TL1994\ 74JOC546Ł[ In a similar manner\ lithiation of the sulfonyl oxiranes "040# followed by treatment with diphenyl diselenide gave the oxidised selenothio!ortho!ester derivatives "056# in yields of 14Ð81) "Scheme 25# ð80JCS"P0#2980Ł[ S
S
i, BunLi, THF, –78 °C
O
ii, MeSeSeMe
S
50%
O
Li+
–
SeMe
O Scheme 35
O
R1
i, BunLi, THF, –100 °C
SO2Ph
O
R1
–
R2
R2
SO2Ph
ii, PhSeSePh
Li+
25–92%
(151)
O
R1
SO2Ph R2
SePh (167)
Scheme 36
5[92[5 MIXED SULFUR AND SELENIUM FUNCTIONS Monoselenodithio! and diselenomonothio!ortho!esters are mixed sulfur and selenium functions which bear one and two selenium substituents respectively[
5[92[5[0 Methods for the Preparation of Functions R0C"SR1#"SR2#SeR3 5[92[5[0[0 From R0C"X0#"X1#X2 1!Chloro!0\2!dithianes react with areneselenolates to give 1!areneseleno!0\2!dithianes[ Thus\ di! thianes "058\ R0 H^ R1 H\ Me\ OMe\ F\ Cl\ NMe1\ CF2# were prepared from 1!chloro!0\2! dithiane and the appropriate sodium areneselenolates "prepared by reduction of the corresponding diaryl diselenide using either sodium borohydride or metallic sodium and ultrasound# ð77JOC2655Ł[ Similar reaction of the 1!chloro!3\5!dimethyl!0\2!dithiane "057\ R0 Me# with sodium "p!methoxy! benzene#selenolate gave the selenodithio!ortho!ester "058\ R0 Me^ R1 OMe#\ which was obtained as a ca[ 4 ] 0 mixture of diastereoisomers "Equation "092## ð77JOC4557Ł[ R1
Na+ –Se
S
R2, C6H6
R1 S
Cl
Se
S R1
R2
(103)
S R1
(168)
(169)
5[92[5[0[1 From selenodithiocarbenium salts 1!Methanethio!0\2!selenothiolium salts are reduced to 1!methanethio!0\2!selenothioles by sodium borohydride[ Reduction of the ~uorosulfonate salt "069# gave the 1!methanethio!0\2!selenothiole "060# in 69) yield "Equation "093## ð79H"03#160Ł\ and similar treatment of the iodide salts "061\ R H\ Me# produced the analogous selenothioles "062\ R H\ Me# ð64TL0148Ł[
091
Three Chalco`ens Se Ph
Se
NaBH4, EtOH
SMe FSO3–
+
SMe
70%
S
Ph
(170)
(171) Se
Se SMe I–
+
R
(104)
S
SMe
S
S
R
(173)
(172)
5[92[5[0[2 From dithioacetals Selenodithio!ortho!esters may be prepared by the selenation of lithiated dithioacetals[ Deprot! onation of 0\2!dithiane using n!butyllithium followed by reaction with p!nitrobenzeneselenyl cyanide produced the 1!seleno!0\2!dithiane "063# in 12) yield "Scheme 26# ð77JOC2655Ł[ However\ treatment of lithiated 0\2!dithiane with the diaryl diselenides "064\ R OMe\ CF2# gave only very low yields of the selenated compounds "065\ R OMe\ CF2# ð75CJC621Ł[ S
O2N
S
BunLi, THF, –20 °C
–
S
Li+
SeCN
S Se
23%
S
NO2
S (174)
Scheme 37 S
R
Se Se
Se
R
R
S (176)
(175)
5[92[5[1 Methods for the Preparation of Functions R0C"SR1#"SeR2#SeR3 5[92[5[1[0 From diseleno!ortho!esters Pinto et al[ ð78H"17#278Ł reported the preparation of the diselenothio!ortho!esters "066\ R H\ Me# from the corresponding O!ethyl diseleno!ortho!esters by treatment with benzenethiol[ The starting diseleno!ortho!esters were generated by the boron tri~uoride etherate catalysed reaction between dilithium diselenides and triethyl ortho!formate "see Section 5[92[4[3[0#\ and were used in situ[ Se OEt R
Copyright
#
Se
1995, Elsevier Ltd. All R ights Reserved
Se
PhSH
SPh R
(105)
Se (177)
Comprehensive Organic Functional Group Transformations
6.04 Functions Containing a Chalcogen and Any Other Heteroatoms Other Than a Halogen MARTIN J. RICE ZENECA Agrochemicals, Bracknell, UK 5[93[0 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 04 ELEMENT 5[93[0[0 Functions Bearin` Chalco`en and Nitro`en 5[93[0[0[0 Functions bearin` oxy`en and nitro`en 5[93[0[0[1 Functions bearin` sulfur and nitro`en 5[93[0[0[2 Functions bearin` selenium and nitro`en 5[93[0[1 Functions Bearin` Chalco`en and P\ As\ Sb or Bi 5[93[0[1[0 Functions bearin` oxy`en and P\ As\ Sb or Bi 5[93[0[1[1 Functions bearin` sulfur and P\ As\ Sb or Bi 5[93[0[1[2 Functions bearin` selenium and P\ As\ Sb or Bi 5[93[1 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLY A GROUP 04 ELEMENT
093 093 093 000 004 005 005 008 012
013 013 013 013 015 029 029 029 021
5[93[1[0 Functions Bearin` Chalco`en and Boron 5[93[1[1 Functions Bearin` Chalco`en and Silicon 5[93[1[1[0 Functions bearin` oxy`en and silicon 5[93[1[1[1 Functions bearin` sulfur and silicon 5[93[1[1[2 Functions bearin` selenium and silicon 5[93[1[2 Functions Bearin` Chalco`en and Germanium 5[93[1[2[0 Functions bearin` oxy`en and `ermanium 5[93[1[2[1 Functions bearin` sulfur and `ermanium 5[93[2 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY A GROUP 04 ELEMENT OR A METALLOID 5[93[2[0 Functions Bearin` Oxy`en and a Metal 5[93[2[0[0 Functions bearin` two oxy`ens and a metal 5[93[2[0[1 Functions bearin` oxy`en\ silicon and a metal 5[93[2[0[2 Functions bearin` oxy`en and two metals 5[93[2[1 Functions Bearin` Sulfur and a Metal 5[93[2[1[0 Functions bearin` sulfur\ oxy`en and a metal 5[93[2[1[1 Functions bearin` two sulfurs and a metal 5[93[2[1[2 Functions bearin` sulfur\ boron and a metal 5[93[2[1[3 Functions bearin` sulfur\ silicon and a metal 5[93[2[1[4 Functions bearin` sulfur and two metals 5[93[2[2 Functions Bearin` Selenium and a Metal 5[93[2[2[0 Functions bearin` selenium\ sulfur and a metal 5[93[2[2[1 Functions bearin` two seleniums and a metal
092
022 022 022 022 022 022 022 023 024 024 024 024 024 024
093
Chalco`en and Any Other Heteroatoms 025 025
5[93[2[2[2 Functions bearin` selenium\ phosphorus and a metal 5[93[2[2[3 Functions bearin` selenium\ silicon and a metal
5[93[0 FUNCTIONS CONTAINING CHALCOGEN AND A GROUP 04 ELEMENT The compounds in this class have been the subject of several reviews ð58ZC190\ B!69MI 593!90\ 60S05\ 66UK574\ B!68MI 593!90\ 68T0564\ 74HOU"E4#2Ł[
5[93[0[0 Functions Bearing Chalcogen and Nitrogen Functional groups bearing chalcogen and nitrogen are available by modi_cation of precursors which contain sp2! or sp1!carbon atoms\ via cycloadditions or by other miscellaneous methods[ This general order is adhered to throughout this section[
5[93[0[0[0 Functions bearing oxygen and nitrogen "i# Functions bearin` two oxy`en and one nitro`en substituent The functional group containing two ether type oxygens and one amine type nitrogen singly bonded to a carbon is most commonly referred to as an amide acetal[ In the majority of cases\ all the heteroatoms are substituted further[ Exceptions are the cyclols which have one unsubstituted oxygen atom[ "a# From sp2!carbon compounds[ Amide acetals can be accessed by transacetalation of other amide acetals ð50LA"530#0\ 52AG185\ 53CCC534\ 54HCA0635\ 57CB30Ł with alcohols[ Typically\ the starting material is N\N!dimethylformamide dimethyl acetal "0#[ The uncatalysed reaction is driven to completion by the removal of generated methanol by distillation[ The use of sterically hindered alcohols can\ however\ lower the reaction yields signi_cantly[ Cyclic amide acetals "1# are available from diols "Scheme 0# ð50LA"530#0\ 53CCC534\ 57CB30Ł[ Transamidation can be achieved with high boiling amines such as morpholine and piperidine ð50LA"530#0\ 55USP2128408Ł[ Simultaneous trans! acetalation and transamidation has also been reported ð53CCC534Ł[ OR
ROH
Me2N
OMe
OR
Me2N HO
OMe
OH
(1)
O Me2N O
Scheme 1
(2)
Cyclols "3# are relatively rare in the literature\ existing as equilibrium mixtures with the cor! responding ring!opened hydroxyamides "2#\ and more commonly they have been proposed as transient reaction intermediates "Equation "0## ð59CRV43\ 52CCC1939\ 52TL328\ 53JOC1658\ 53TL36\ 55UKZ193\ 57TL1602Ł[ O!Alkylation ð51TL690\ 52T0550\ 52T0564\ 54T2426Ł generates fully substituted amide acetals[ O
HO
O (1)
HO
NH (3)
R
R
NH (4)
Symmetrical amide acetals "4# are obtained from ortho!esters with a variety of nitrogen nucleo! philes such as sulfonamides "Equation "1## ð50JOC3204\ 54AJC0856\ 79JOC3927\ 71JCS"P0#1760\ 77JHC896Ł\ ureas ð42JA560\ 52HCA1295Ł\ imidazoles ð79JOC3927Ł and di~uoroamine ð56JA605Ł[
094
Chalco`en and Group 04 OR2 OR2 OR2
R1
R3R4NH
R1
OR2 NR3R4 OR2 (5)
(2)
Under Lewis acid catalysis\ isocyanates will react to give N!carboxy compounds "5# "Equation "2## ð51AG"E#481\ 55GEP0045679Ł[ Cyanide can be displaced from "a!alkoxy!a!alkylamino#acetonitriles "6# ð61CB0239Ł or\ in addition to one of the alkylamino groups\ from a\a!bis"dialkylamino# acetonitriles "7# by alkoxides ð38LA"451#118\ 61CB0239Ł[ Both halogens in a\a!di~uorotrialkylamines "8# have been replaced by alcohols ð52USP2981526\ 53USP2010973\ 54USP2103301\ 72TL0924Ł[ Chloro! diaryloxymethanes have been used to generate diaryloxymethyltriethylammonium chlorides "09# with triethylamine ð47JPR"6#69Ł[ Such reactive compounds give amide acetals on further reaction with amines ð61S21\ 61S307\ 62S312\ 64S161Ł[ OR1
OR1
R2NCO, BF3
R1O
R1O
OR1
NR12
F
NMe2
NC
NMe2 (8)
(7)
OAr NR22
R1
NC OR2
(3) NR2CO2R1 (6)
Cl–
Et3N+
F
OAr (10)
(9)
"b# From sp1!carbon compounds[ The halogen in N\N!dialkyliminium chlorides "00# can be dis! placed on treatment with alkoxides to yield amide acetals "01# "Equation "3## ðB!69MI 593!90\ 61TL3106\ B!68MI 593!90Ł[ In a similar manner\ alkoxide can be displaced from alkoxyiminium salts "02# ð50LA"530#0\ 57PAC408\ B!69MI 593!90\ B!68MI 593!90Ł and thiolate from alkylthioiminium salts "03# ð56BCJ1530Ł[ Lactam acetals are also accessible by this methodology ð52USP2981526\ B!68MI 593!90Ł[ In addition\ pyridine has been demonstrated to react with the oxonium salt "04# to give the pyridinium species "05# ð60S201Ł[ The adduct "06# is formed by capture of the N!acyloxazolium salt with methoxide ð64JCS"P0#0291Ł[ Cl H
OR2
NaOR2
R12N
+
NR12 (11)
(12)
OR2 H
(4) OR2
SEt
+
NR12 (13)
H
+
NMe2 (14) O N
+
+
EtO
OEt BF4– (15)
OEt
N
N O
O
OEt (16)
O
MeO (17)
Formamide acetals are produced by the reaction of N\N\N?\N?!tetrasubstituted formamidium salts with sodium alkoxides ð59AG845\ 51JOC2553\ 52GEP0035781\ 53CCC534Ł[ Tetrakis"dimethylamino#ethene "07# is converted by methanol into a mixture of amide acetals "08# and "19# ð61T0854Ł[ Hexa! ~uoropropene "10# combines with diethanolamine "11# to generate an azadioxabicycloð2[2[9Łoctane
095
Chalco`en and Any Other Heteroatoms
"12# ð61TL2846Ł[ Similar systems\ such as "14#\ are obtained by the reaction of the sodium salts of dialkanolamines such as "13# with nitriles "Scheme 1# ð62AG"E#885Ł[ Me2N
NMe2
Me2N
OMe
MeOH
NMe2
OMe
(18)
HO
Me2N
(19)
H N
F
F
F
CF3
(20) F3C
F
O
O
Et3N
+
OH
OMe NMe2 OMe
MeO
+
Me2N
N (23)
(21)
(22)
i, Na ii, EtCN
H N
HO
O
OH
O N (25)
(24) Scheme 2
"c# Cycloaddition methods[ The unsubstituted ketene acetal "15# reacts with isocyanates to give barbituric acid acetals "16# ð48MI 593!90\ 51AG"E#220\ 55CB2781Ł while the cyclic analogue "17# generates the b!lactam "18# ð77TL1216Ł[ Similarly\ tetramethoxyethene gives the azetidin!1!one "29# "Scheme 2# ð48MI 593!90\ 53AG"E#279Ł[ Ketene acetals will also react with nitrosobenzene\ with dialkyl azo! dicarboxylates ð60CB762Ł and with ketenimines ð65IZV747Ł to give four!membered ring products "20#\ "21# and "22#[ O
O OEt
EtO
PhNCO
Ph
NHPh
PhNCO
N OEt
OEt
EtO
O
N Ph (27)
(26) O
O
PhNCO
O
O
N
(28)
Ph (29)
MeO
OMe
MeO
OMe
OEt
PhNCO
O
MeO MeO
O
N MeO Ph MeO (30) Scheme 3
MeO MeO
O
N MeO Ph MeO (31)
MeO MeO MeO MeO
CF3 CO2Me N
Ph
F3C
N
N
OEt OEt
CO2Me (32)
(33)
Dichloroketene acetals such as "23# react with sulfamyl chlorides to give four!membered ring products "24# "Equation "4## ð56JA1491\ 61JA5024Ł[ a\b!Unsaturated ketones combine with ynamines ð69CR"C#357Ł and with 0!dialkylamino!0!alkylthioethenes ð56BCJ1530Ł to give bicyclic amide acetals "Scheme 3# ð57TL386Ł[
096
Chalco`en and Group 04 O O
O
EtNHSO2Cl
Cl
(34)
(35)
O
2
(5)
SO2
Cl
Cl
Cl
Et N
O
O
2
R2N
R2N O
MeS
O NR2
Scheme 4
An unsymmetrical bicyclic amide acetal "26# has been obtained by treatment of the dihydrooxazole "25# with benzonitrile oxide ð60AG"E#709Ł[ Dialkoxydihydro!0\1\2!triazoles such as "27# are produced by the reaction of azides with some ketene acetals ð52G831\ 57G570\ 61JHC0976\ 65JHC194Ł[ Cyclo! propanone acetals such as "28# undergo ring expansion with aryl isocyanates to give g!lactam acetals "39# "Scheme 4# ð76JCR"S#251Ł[ Ph N
+
O
Ph
N
N+ O– O
(36)
(37) MeO
MeO PhN
N+
N O
N–
N N
MeO
+
N
MeO
Ph (38)
MeO
O
OMe PhNCO
EtO2C
H
EtO2C
N
Ph
OMe H OMe (40)
H (39) Scheme 5
"d# Miscellaneous reactions yieldin` amide acetals[ The imidate "30# has been oxidized by mcpba to the corresponding oxaziridine ð60TL3408\ 62TL0796Ł[ t!Butyl hypochlorite has been used to oxidise a 3!oxa!b!lactam "31# to the amide acetal ð71H"07#190Ł[ Benzoylhydrazones "32# react with lead tetraacetate to give 1\4!dihydro!0\2\3!oxadiazoles ð56TL2490\ 57CB2740Ł[ Reductive conditions are exempli_ed by the reaction of N\N!dimethylformamide and N\N!dimethylacetamide with 0\2!dibro! moketones and a zinc:copper couple to give amide acetals "33# "Scheme 5# ð61JA2190Ł[ The insertion of ethoxycarbonylnitrene\ generated by photolysis of ethyl azidoformate\ into acetals ð56T34Ł and ketene acetals ð61JHC0976Ł leads to N!carboxy amide acetals such as "34#[ Dichlorocarbene reacts with dialkylamines and sodium alkoxides to give the amide acetals HC"OR0#NR11 resulting from insertion and double halogen displacement ð53GEP0050174\ 58LA"614#04\ 58RTC178Ł while the diazo compound "35# on photolysis undergoes cyclisation to the dihydrooxazole "36# ð63JHC418Ł[ Epoxides add to dihydrooxazoles "37# and 4\5!dihydro!3H!0\2!oxazines to give bicyclic amide acetals such as "38# ð55AG"E#764\ 55AG"E#783\ 55LA"587#063Ł[ The bicyclic amide acetal "49# was obtained by the addition of diketene to the C1N bond of a chiral oxazoline "Scheme 6# ð80TL486Ł[ N!Methylpyrrole undergoes anodic oxidation in methanol to generate the symmetrical product "40# ð55JOC3943Ł[ Under basic conditions\ the diazene oxide "41# reacts with methanol to give the azo compound "42# ð67JOC0348Ł[ Ozonides "43# are formed by the reaction of ozone with indoles
097
Chalco`en and Any Other Heteroatoms MeO
N
mcpba, CH2Cl2
But
MeO
(41) Ph
O
Ph
O
HN
OMe O
LiOMe, ButOCl
N
N
O-TMS
O
O
O
Ph (42)
Ph
Ph
Et Pb(OAc)4
Ph
N Et
O-TMS
O
O
O
But
O
HN
O
Ph
N
N H (43)
Et Et
O
N N O
Ph OAc R5
NMe2
O
O
O R1
R3 R4
Br
Br
Zn–Cu
+ R5CONMe2
R2
R1
R4
R2 R3 (44)
Scheme 6
O
O
N2 Ph MeO
N H O (45) Ph
H N
CO2Et OMe
N
OEt N
MeO
OMe (47) O
N
LiCl
+ Et
O
hν
(46)
O
CO2Et
O
hν
+ N3CO2Et
O
Ph
Ph O
Et (49)
(48) H O
O
N But
O (50) Scheme 7
ð41JA2744Ł[ Compounds of this type have also been obtained by cyclisation of hydroperoxides ð41CB838Ł[ The reaction of some cyclic ortho!esters with TMS azide leads to the formation of displacement products such as "44# "Scheme 7# ð68TL402Ł[ "ii# Functions bearin` one oxy`en and two nitro`en substituents Functions bearing two nitrogens and one oxygen are known commonly as ester aminals[ As with the amide acetals\ they are synthetically accessible from sp2! and sp1!carbon compounds\ by cyclisations\ by cycloadditions and by other miscellaneous methods[
098
Chalco`en and Group 04 Me
Me MeO
hν
N
N
OMe
MeO
OMe (51)
Ph
+
–O
Ph
Et3N, MeOH
N N
N N
OPrn
OPrn MeO (53)
(52) Scheme 8
R
O O
N H (54)
N3
O
O
O
Ar (55)
"a# From sp2!carbon compounds[ Some examples of the formation of ester aminals by dis! placement reactions are shown in Scheme 8[ Treatment of bis"dimethylamino#acetonitrile with sodium ethoxide yields the ester aminal "45# ð61CB0239Ł[ The base induced cyclisation of 0!chloro! 4\4\4!trinitropentan!1!ol "46# occurs with the elimination of nitrite ð54AG316Ł[ All three halogens are displaced in the reaction of chloroform with aziridine and sodium methoxide ð58LA"614#04Ł[ Reaction of triethyl ortho!acetate with the 1!aminobenzenecarboxamide "47# leads to the 1! ethoxyquinazolinone "48# ð89JHC0842Ł[ NMe2
NaOEt
NC
NMe2 EtO
NMe2
NMe2 (56)
C(NO2)3 Cl
NO2
Cl O
OH (57)
CHCl3
+
O N H
NaOH
+
H N
NO2
OMe NaOMe
N
OEt OEt OEt
NH2
N
O AcOH
N N H OEt (59)
(58) Scheme 9
"b# From sp1!carbon compounds[ Electron!de_cient heterocycles undergo a range of related additions of water and alcohols ð73CHEC"2#80Ł[ Some examples of these reactions are shown in Scheme 09[ {Covalent hydration| is exempli_ed by the addition of the elements of water to the tetrazoloquinazoline "59# ð54JOC718\ 56KGS0985Ł[ An intramolecular addition occurs when the dini! tropyridine "50# is treated with base ð57TL548Ł[ Diethylamine reacts with 4!phenyl!0\1\3!dioxazolin! 2!one "51# ð61JPR034Ł[ An analogous reaction occurs when 0\2\3!oxadiazolium salts are treated
009
Chalco`en and Any Other Heteroatoms
with secondary amines leading to tertiary products^ primary amines lead to ring!opened products ð60JCS"C#398Ł[
N N
N N
N
2M HCl
N
HN
N N
(60)
OH
NO2
O 2N
N
NO2
O2N NaOMe
N
O (61)
Ph
O
O
OH
N H O Ph
O
Et2NH
N
Et2N
O
O O N H
O
(62) Scheme 10
In a reaction analogous to that with the oxazoline "37#\ epoxides have been demonstrated to react with dihydroimidazoles and tetrahydropyrimidines to give ester aminals ð69LA"631#017Ł[ "c# Cycloaddition methods[ Reaction of p!nitrophenyl isocyanate with O!alkyllactims such as "52# leads to 3!alkoxy!0\2!diazetin!1!ones "Equation "5## ð62TL0108Ł[ O N
OMe
NCO
N
N
+
(6)
OMe
O2N
NO2
(63)
"d# Miscellaneous reactions yieldin` ester aminals[ Addition of a!tetralone to the bisurea "53# in ethanolic hydrogen chloride a}ords a 1!hydroxyhexahydroquinazoline "54# ð55IZV87Ł[ A 2! "dimethylamino#oxaziridine "55# is formed by photocyclisation of the nitrone "56# ð60JA3964Ł[ The reaction of hydrazoic acid with ethoxypropyne gives bisazide "57# "Scheme 00# ð46RTC838Ł[
OH HN
O H2NCONH
Ar
+ Ar
H2NCONH (64) Ph
(65)
NMe2 hν
Me
N+
O Me2N
N Ph (66)
O–
(67)
OEt
NH
+ HN3
Scheme 11
Et
Me
N3 OEt N3 (68)
000
Chalco`en and Group 04 5[93[0[0[1 Functions bearing sulfur and nitrogen "i# Functions bearin` one sulfur\ one nitro`en and one oxy`en substituent
Functional groups bearing oxygen\ sulfur and nitrogen are nonsymmetrical\ and this reduces the number of synthetic routes available for their preparation compared to their symmetrical analogues[ "a# From sp2!carbon compounds[ Two examples of formation of this functional group by dis! placement are shown in Scheme 01[ Triethyl ortho!formate reacts with 1!thiolbenzamide to give a dihydrobenzothiazine "58# ð58T4884Ł[ Displacement of aniline from the 0\2\3!thiadiazoline "69# by ethanol produces the 4!ethoxy analogue "60# ð65ACS"B#726Ł[ O CONH2
OEt
+
EtO
2-Naphthyl-SO3H
NH
OEt
SH
N
Ph
N
Ph
S (69)
EtOH
N
Ph
S
N S
Ph NHPh (70)
OEt
Ph Ph
OEt (71) Scheme 12
1
"b# From sp !carbon compounds[ The N!alkylbenzothiazolium cation "61# reacts with the 1! hydroxybenzaldehyde "62# to give the spiro compound "63# ð61HCA0671Ł^ there are other examples of intramolecular cyclisation of benzothiazolium cations with phenolic ð58T4884Ł and ketonic functions ð89IJC"B#079Ł in the presence of base\ and related reactions of thiazoles ð73H"11#170Ł[ The dime! thylformamide monothioacetal "64# is prepared by O!methylation of N\N!dimethylformamide with dimethyl sulfate\ and subsequent interception of the iminium cation "65# with sodium ethanethiolate ð60BSF2243Ł[ An alternative approach\ the interception of a thioimidate with an alcohol\ has also been reported ð73H"11#02Ł[ Reaction of 1!"1?!thiolphenyl#dihydroimidazole "66# with phthalolyl chloride gave the spiro thioacetal "67#[ In this reaction it may be the cyclic tautomer "68# of phthaloyl chloride which is the reactive species "Scheme 02# ð77LA488Ł[ "c# Cycloaddition methods[ Benzonitrile oxide can undergo 0\2!dipolar cycloadditions to C1S or to C1N bonds which lead to amide thioacetals[ Two examples of such reactions\ leading to the oxathiazole "79# ð68CB0762Ł and to the fused azetidine "70# ð89TL012\ 80JHC370Ł are shown in Scheme 03[ The reaction of keteneÐsulfur dioxide adduct with the 1!aryldihydrooxazoles "71# gives the cycloadduct "72# ð58JHC618Ł[ The dihydroindole "74# was obtained from the reaction of dichloro! ketene with the indole "73# "Scheme 04# ð78JOC0671Ł[ "d# Miscellaneous reactions yieldin` amide monothioacetals[ 3!Thio!b!lactam "75^ R H# under! goes oxidation with lead tetraacetate ð63JCS"P0#11Ł or with t!butyl perbenzoate in benzene ð68CC374Ł to give O!acylated derivatives "75^ R OCOMe or OCOPh#[ Phenacyl bromide reacts with phenyl! propiolic thioanilide "76# in the presence of acetone to produce a 0\2!oxathiole "77# "Scheme 05# ð64LA847Ł[ "ii# Functions bearin` two sulfur and one nitro`en substituent There are many parallels that can be drawn between the preparation of thioamide acetals and their oxa analogues[ It is likely that many of the principles behind the methods for preparation of the latter could be applied to the former[ "a# From sp2!carbon compounds[ Reaction of amide acetals with thiols provides a route to both acyclic and cyclic thioamide acetals "78# and "89# "Scheme 06# ð58BSF221\ 69BSF1902Ł[ Replacement of the alkoxy function of the dithio!ortho!ester "80# has been demonstrated to give the amide dithioacetal "81# ð79PJC034Ł[ a!Chlorothioacetals such as "82# are converted into amide thioacetals "e[g[ "83## by treatment with amines ð50LA"530#10Ł[ "b# From sp1!carbon compounds[ The reaction of alkoxyiminium cations such as "65# with thiolate salts in excess leads to amide thioacetals HC"SR0#1NR11 ð54IZV1068\ 62CB2614Ł[ Chloroiminium salts react with thiols in a similar way ð59MI 593!90Ł and "alkylthio#iminium cations "84# have also been
001
Chalco`en and Any Other Heteroatoms CHO HO
S
piperidine
+ N+
OMe
MeO S
MeO
N
O Me MeO (74)
NO2
Me (72)
(73) OMe
OMe
EtS–
Me2N
N+
SEt
Me (76)
Me
NO2
(75) N
O
N
+
N H
+
S
PhCH2NEt3Cl–
Cl
SH
N
Na2CO3
O
O
Cl
(77)
(79)
(78)
O Cl Cl O Scheme 13
O Ph
Ph S
Ph
N O
N+ O–
Ph
N
N
O
S
CN (80)
CN
SEt
SEt Ph
O
N+ O–
N
N
N
Ph (81) Scheme 14
i, SO2 ii, ketene
N O2N
O
O2S O2N
N
O
O
(82)
(83) Cl O–
S+ N Me SO2Ph (84)
+
Cl3CCOCl
Zn–Cu
Cl O O
N
SMe
SO2Ph (85) Scheme 15
O
002
Chalco`en and Group 04 Br
Ph
R
Br
SMe
NHPh
O N O
CO2Me
+
Br
Ph
O
Ph
S NHPh
S Ph
(86)
(87)
(88)
Scheme 16
SC7H15
HSC7H15
Me2N SC7H15 (89)
OMe Me2N OMe HS
S
SH
S NMe2 (90)
Scheme 17
Ph Ph
Ph
S
Ph
S
S
O
S SMe
SMe
N
O
Me2N
Cl
SMe
SMe
OMe (91)
(93)
(92)
(94)
intercepted with thiols to give thioamide acetals ð54BCJ1096\ 55BCJ1994\ 72CI"L#194Ł[ 0\2!Thiazolium cations "85# undergo reaction with azide anions and with amines to give the addition products "86^ X N2 or NR1# ð54JCS21\ 65BCJ2456\ 65JPR016\ 79JOC1913\ 70JCS"P0#507Ł[ Reduction of the C1N bond of the iminium salt "87# with sodium borohydride yields the corresponding amide thioacetal ð58CPB0813Ł[ A more unusual example is that provided by the reaction of the tris"alkylthio#borane derivatives "88# with amides "Equation "6## ð55IZV253\ 68ZN"B#888Ł[ Ph S S+
SR2
R1
S N+
S
X–
X +NR3
S
2
(95)
S (97)
(96)
SR3
O
+ R1
(98)
R3S
R1
B
NR22
SR3
SR3 NR22 SR3
(7)
(99)
"c# Cycloaddition methods[ The ð1¦1Ł cycloaddition of ketenes to iminodithiocarbonate esters has been used as a route to b!lactams which incorporate the amide dithioacetal function[ Examples with cyclic ð46CB1359\ 62JHC680Ł and acyclic ð65JOC0001\ 76S889Ł iminodithiocarbonates are shown in Scheme 07[ Dihydrothiazoles also react with the keteneÐsulfur dioxide adduct "in a manner
003
Chalco`en and Any Other Heteroatoms
analogous to that shown for the oxazoline "71## to give products which contain this functionality ð58JHC618Ł[ S
MeS
+ ClCOCH2OMe
SMe S
MeO
Et3N
N
N
O
MeS
MeS MeS
SMe Et3N
+ ClCOCH2ON3
N
N3
N O
CO2But
CO2But Scheme 18
"d# Miscellaneous reactions yieldin` amide thioacetals[ Photo!rearrangement of N!"ethoxy! acetyl#tetrahydro!0\2!thiazine!1!thione gives the thiazolidinone "099# "Equation "7## ð75TL0224Ł[ There are several routes to compounds containing methanesulfonyl functions[ The azo compound "090^ R H# has been obtained by the reaction of bis"methanesulfonyl#methane with benzene! diazonium chloride ð40RTC622Ł and from its analogue "090^ R SMe# by reaction with piperidine ð40RTC781Ł[ Reaction of diazomethane with the oxime "091# gave the N!methoxyaziridine "092# ð49RTC0112Ł[ S
O EtO
N
S
S
S
hν
EtO
(8)
N O (100) OMe
R
N NPh SO2Me SO2Me
N
N SO2Me
SO2Me
MeO2S
(101)
OMe
MeO2S (103)
(102)
"iii# Functions bearin` one sulfur and two nitro`en substituents "a# From sp1!carbon compounds[ Addition to alkylthioiminium salts "093# by sodium azide and subsequent cyclisation gives thiatriazoles "094# ð63JCS"P0#439Ł[ Amines will add in a similar manner to the C1N bond of thiazolium cations such as "095# ð60CPB1111\ 76JOC1904Ł and to 2!methylthio! 0\1\3!dithiazolium cations "096# ð63JCS"P0#439Ł[ Phenylmagnesium bromide adds to both the C1C and the C1N bonds of 4!arylidine!1!phenyliminothiazolidin!3!ones "097# ð53T14Ł[ Treatment of hydrazonyl halides with thioamides leads to 1\1!disubstituted dihydro!0\2\3!thiadiazoles "098# ð65ACS"B#726Ł[
+
N O
Ar
N N
SMe Ph
N
S
N
Ph
Me
+
N
S
O
(104)
(105)
(106)
"b# Cycloaddition methods[ Cycloaddition of cyclopentadiene to thiocarbonylbis"0\1\3!triazole# "009# gives the adduct "000# ð79JOC2602Ł[ Diphenylethyne reacts under photochemical conditions to the C1S bond of "001# to give both four! "002# and six! "003# membered ring adducts "Scheme 08# ð65TL2452\ 79LA762Ł depending on the wavelength employed[ Acid chloride derived ketenes undergo
004
Chalco`en and Group 04 O +
S
S
H N N
H N
Ph
SMe
N (107)
Ph
Ph
Ph
S
NPh
S (108)
Ph
NHPh
(109)
ð1¦1Ł cycloaddition with tetrahydro!1!alkylthiopyrimidines to yield thio substituted b!lactams such as "004# ð73TL0738Ł[ Trichloroacetyl isocyanate reacts with mesoionic thiazoles to give cycloadducts such as "005# ð65ACS"B#726\ 65JOC702Ł[ Amide thioacetals react with aryl isocyanates to furnish the imidazolinediones "006# ð62CB2614\ B!68MI 593!91Ł^ a similar reaction occurs with N!alkyl!0\2\3! thiadiazolium salts ð77LA594Ł[ "c# Photoreduction[ The C1S bond of 0\2!diphenyl!1!thioparabonate "007# undergoes photo! reduction in ethanol ð58BCJ1212Ł[ N
N N
N
N
N
N
N
+
N
S N N
S (110)
N
(111) Ph
Ph Me N
S Me
N
Me
N
O
+
Ph
S
hν
Ph
Me
Ph
N
or
Me
N
S
O
N
Me
O O (112)
O
O (113)
(114)
Scheme 19
PhO MeS CBZ N
N
Ph
Ar
O
O
O
N
S
N
RS
COCCl3
Ar (116)
(115)
O
N
Me2N
O Ph
N O (117)
Ar
O
N
N
Ph
S (118)
5[93[0[0[2 Functions bearing selenium and nitrogen "i# Functions bearin` one selenium\ one oxy`en and one nitro`en substituent The 1!methoxydihydroselenazole "008^ Ar 3!PhC5H3# has been obtained from the corresponding N!methylselenazolium cation by reaction with sodium methoxide ð70ZOB0731Ł[ Similarly\ treatment of a N!alkylbenzoselenazolium cation "019# with a 1!hydroxybenzaldehyde derivative generates a 1!spiro derivative "010# ð60BSF445\ 80CL0762\ 82CL02Ł[ R1 N Me N Ph
Ar
Se OMe (119)
R1 N+ Se (120)
Se O R2O (121)
NO2
005
Chalco`en and Any Other Heteroatoms
"ii# Functions bearin` one selenium\ one sulfur and one nitro`en substituent Selenium substituted b!lactams such as "011# have been obtained by cycloaddition of ketenes to 1!alkylselenothiazolines ð75JAP50047875\ 75JOC3626\ 76NKK0336Ł[ SeMe S
MeO
N O
CO2Me (122)
"iii# Functions bearin` one selenium and two nitro`en substituents Two examples of such compounds are provided by the selenide "012# which was obtained from 0\0!dinitroethane and benzeneselenyl chloride ð71IZV050Ł and by the 0\2\3!selenadiazole "013#\ which is formed by addition of a hydrazonyl chloride to the C1Se bond of a selenamide ð89ZOR0018Ł[ Ph
Ph N
N
NO2 SePh NO2
N
Se
O (124)
(123)
5[93[0[1 Functions Bearing Chalcogen and P\ As\ Sb or Bi 5[93[0[1[0 Functions bearing oxygen and P\ As\ Sb or Bi "i# Functions bearin` two oxy`en and one phosphorus substituent Ortho!esters and amide acetals may be converted into phosphorus containing functions by treatment with a phosphorus"III# nucleophile ð75MI 593!90Ł[ A 1!trimethylammonium!0!2!dioxane "014# reacts with isopropyl diphenylphosphinate to give the phosphine oxide "015# "Equation "8## ð77JOC2598Ł[ Similarly\ triethyl phosphite combines with 1!trimethylammonium!0\2!dioxolane a}ording the phosphonate ester ð63JPR802Ł[ Chlorodiphenylphosphine and dichloromethyl! phosphine react with ortho!formate esters to give the phosphine oxides "016# and phosphonate esters "017#\ respectively ð72TL0292\ 78T2676Ł[ Related reactions with hypophosphorous acid ð79AJC176Ł and with diethyl phosphinate ð66TL1876Ł have been reported[ Triethyl phosphite\ in combination with phosphorus trichloride and zinc chloride\ reacts with triethyl ortho!acetate to form the phosphonate diester acetals "018# ð62S436Ł[ The adduct "029# formed from phosphorus trichloride and acetaldehyde reacts with triethyl ortho!formate to give the mixed phosphonate diester acetal "020# ð89CC0022Ł[ O
O N+Me3
+
OPri
Ph2P
PPh2
O (125)
O (126)
O
Me
Ph2P OR (127)
O
OR
OR
P OEt OR (128)
O
O
OEt
EtO P OEt OEt (129)
(9)
006
Chalco`en and Group 04 Cl
O
Cl O (130)
P O MeO
PCl2
OMe
OMe (131)
Dialkyl phosphinates react with the 2!acetylcoumarin to give the hemiacetal "021# ð80PS"46#100Ł[ Hydration of a!phosphono!a!oxo esters "022# proceeds in high yield to give the hydrates "023^ R H#[ Similarly\ alcohols yield the corresponding hemiketals "023^ R alkyl# "Scheme 19#[ The yield is higher for methanol than for t!amyl alcohol as branching leads to steric congestion at the quaternary centre ð78CC135Ł[ 1\1!Dimethylpropylidynylphosphine "024# undergoes a double 0\2! dipolar cycloaddition with 3!chlorobenzonitrile oxide to yield the bicyclic product "025# ð73CC0523Ł[ O
O HOP(OR)2
O
PO(OR)2
O
O
OH (132)
O
O
(Et2O)P
H2O or ROH
CO2Et
(Et2O)P
CO2Et
HO
O (133)
OR
(134) Scheme 20
N
Ar
O But But (135)
P O
Ar N (136) (Ar = 4-ClC6H4)
P
Functions which already contain two oxygens and a phosphorus can be elaborated further at the phosphorus atom by standard methods[ Phosphinite acetals "026# undergo an Arbuzov reaction with alkyl iodides "Equation "09## ð77PS"24#218Ł\ and the trimethylsilyl group of the phosphinites "027# is lost in the Arbuzov reaction with alkyl chloroformates which gives the phosphinates "028# ð75ZOB1316Ł[ Examples of aminoalkylation of phosphorus are also known ð78JCS"P0#0208Ł[ O
OR2
R3I
(R1O)2P
R1O
OR2
OR2 (10)
P R3
OR2
(137) R1O
O
OR2 R1 O
P TMS-O (138)
OR2
OR2
P
R3O2C
OR2
(139)
"ii# Functions bearin` one oxy`en\ one phosphorus and one nitro`en substituent Electrochemical oxidation of the a!acylamino phosphonate "039# in methanol with a carbon anode gives the methoxylated compound "030# "Equation "00## ð78T0580Ł[ In an unexpected reaction\
007
Chalco`en and Any Other Heteroatoms
the phosphonate "031# is generated from the treatment of the tosylate "032# with sodium diethyl! phosphinite ð82HCA1396Ł[ O
O
OMe
MeOH, NaCl
Ph
N H
P(OEt)2
Ph
C anode
N H
O
(140)
P(OEt)2
(11)
O
(141)
O
O N
N (EtO)2P
O
OTs O (143)
O (142)
"iii# Functions bearin` one oxy`en and two phosphorus substituents Double addition of phosphinic acids and phosphites to activated carboxylic acid derivatives such as acid chlorides and anhydrides leads to a\a!diphosphino and a\a!diphosphono alcohols\ respectively ð45JA3349\ 56JCS"C#0436\ 60JOC2732\ 62ZAAC"288#0\ 66TL0954\ 67CC174\ 68S70Ł[ An example of the reaction sequence is shown in Scheme 10[ Carboxylic acids combine with phosphorus trichloride bisphosphonic acids ð61MI 593!90\ 71MI 593!90Ł^ thus\ acetic acid gives MeC"OH#ðPO"OH#1Ł1[ Reaction of chlorodiphenylphosphine with acetic acid and then with acetic anhydride a}ords the bisphosphine oxide "033^ R H# via the intermediate ketone "034# "Scheme 11#[ The acetylated analogue "033^ R Ac# is obtained after prolonged reaction times ð66JCS"P0#0787Ł[ Products analogous to "033^ R H# have also been obtained by hydrolysis of acylphosphine oxides ð67ZN"B#738Ł[ O O Ph
O
(MeO)3P
Cl
Ph
HPO(OMe)2
P(OMe)2
HO
P(OMe)2
Ph
P(OMe)2
O Scheme 21
O
O
O
O
AcOH
Ph2PCl
Ph2PH
O
Ac2O
O
Ph2PH
RO
Ph2P
PPh2 PPh2
O (144)
(145) Scheme 22
The diazophosphonate "035# reacts with cyclohexenol in the presence of rhodium acetate to give the ether "036# "Equation "01## ð81JOC067Ł[ Photochemical oxidation of a!diazophosphonates in methanol leads to the formation of products of an analogous type ð71JOC0173Ł[ Cycloaddition of the silylnitronate "037# to the vinylbis"phosphonate# "038# leads to the formation of the dihy! droisoxazole "049# "Equation "02## ð81PS"58#64Ł[ Oxygen functions can also be introduced by reaction with hydrogen peroxide\ as shown in Scheme 12 ð78JOC3161\ 82JOC3048Ł[ O
O
(MeO)2P
P(OMe)2
OH
O (MeO)2P N2 (146)
O
, Rh2(OAc)4
O
P(OMe)2
(12) (147)
008
Chalco`en and Group 04 Ph O
Ph
TMS-O
N+
+ O–
P(OEt)2 (EtO)2P
P(OEt)2
O (148)
N O
O
(13) P(OEt)2
O (150)
(149)
O
O
P(OH)2
P(OH)2
Na2CO3, H2O2, Na2WO4
P(OH)2
HO
O
HO
O
P(OH)2 O
O
P(OR)2
P(OR)2
H2O2, NaHCO3
P(OR)2
O
O
P(OR)2 O
Scheme 23
"iv# Functions bearin` two oxy`en and one arsenic substituent The cycloaddition of the benzoxarsole "040# to tetrachloro!o!benzoquinone gives a product "041# bearing this array of functional groups "Equation "03## ð72TL4370Ł[
As But O
Cl
Cl
Cl Cl
O
Cl
O
+
Cl
O
(14)
As Cl
O O
(151)
Cl
But (152)
5[93[0[1[1 Functions bearing sulfur and P\ As\ Sb or Bi "i# Functions bearin` one sulfur\ one oxy`en and one phosphorus substituent Removal of an acidic proton from a!oxygen substituted phosphonic acid derivatives gives the opportunity for reaction with electrophilic sulfenylating reagents[ Diethyl a!methoxy phosphonate "042# when treated sequentially with a mixture of n!butyllithium and potassium t!butoxide\ elemental sulfur and iodomethane gives the methylthio product "043# ð65TL366Ł[ The use of n!butyllithium alone gives compounds resulting from transesteri_cation ð68JOC1856Ł[ Similarly\ the a!sily! loxyphosphonate "044# reacts with LDA and diphenyl disul_de a}ording the trisubstituted product "045# ð67TL252Ł[ Activation of the a!carbon atom in a!"alkylthio#phosphonates can be achieved by halogenation[ Treatment of the phosphonate "046# with N!chlorosuccinimide gives the a!chloro derivative "047# which\ in the presence of methanol\ is converted into the a!methoxy compound "048# "Scheme 13# ð74TL2368Ł[ The same substitution can be achieved using electrochemical oxidation in methanol ð76S33Ł\ and a similar halogenationÐsubstitution sequence takes place with sulfoxides analogous to "046# ð67JOC1407Ł[ 1!Lithio!0\2!oxathiane reacts with dimethyl thiophosphonyl chloride to give the substitution product "059# ð74JOC551\ 78JPO238Ł[ The ability of a sulfoxide to activate a neighbouring carbon atom is employed in the Pummerer rearrangement of a!sul_nyl phosphonates such as "050# in the presence of acid anhydrides ð66S070\ 67JOC1407\ 75BCJ2182Ł[ In a reaction analogous to that of the diazo compound "035# the ether "051# is formed from the rhodium catalysed solvolysis of the a! diazophosphonate "052# in 1!propanol "Scheme 14# ð81SL864Ł[ Oxygen substitution can also be achieved by photolysis ð71JOC0173Ł[
019
Chalco`en and Any Other Heteroatoms i, BunLi, ButOK ii, S8 iii, MeI
O (EtO)2P
OMe
O (EtO)2P
SMe (154)
(153) O (EtO)2P
O
i, LDA ii, (PhS)2
Ph
(EtO)2P
O
O
NCS, CCl4
SMe
Ph
O-TMS SPh (156)
O-TMS (155)
(EtO)2P
OMe
(EtO)2P
O
MeOH
SMe
(EtO)2P
OMe (159)
Cl (158)
(157)
SMe
Scheme 24
S
S
S
Me2PSCl, THF
Li
P(OEt)2
O
O (160)
O
O
(EtO)2P
O
Ac2O, MeSO3H
SMe
(EtO)2P
(161)
OAc
O PhO2S
SMe
O Rh2(NHCOCF3)4 PriOH
P(OEt)2
PhO2S
P(OEt)2
OPri (162)
N2 (163) Scheme 25
"ii# Functions bearin` two sulfur and one phosphorus substituent 0\2!Dithianes and 0\2!dithiolanes substituted at the 1!position with leaving groups can react with triphenylphosphine ð66TL774\ 70S42Ł\ to give phosphonium salts such as "053# and "054#[ Similarly\ trialkyl phosphites undergo Arbuzov reactions forming phosphonate diesters such as "055# "Equa! tion "04## ð66TL774\ 67JPR144\ 79S016\ 75MI 593!91Ł[ The alternative approach\ the reaction of 1! lithio!0\2!dithiane with an electrophilic phosphorus species\ chlorodiphenylphosphine ð75T0852\ 80JOC4808Ł or diethyl chlorophosphonate ð67S298Ł\ has also been reported[ Phosphorus substituents can also be introduced by nucleophilic addition\ as with the benzo!0\2!dithiolium salt "056# ð65TL2584\ 89CC369\ 80JCS"P0#046Ł[ Reaction of the dithiocarbonate "057# with trialkyl phosphites generates the phosphonates "058# ð64JOC1466Ł[ S
S
+
PPh3 Cl–
S
S (164)
S Cl S
+
PPh3 BF4– (165)
P(OEt)3, Et3N
S
O P(OEt)2
S (166)
(15)
010
Chalco`en and Group 04 NC
S+
S
–
S
NC
S
O
O
BF4 S (167)
NC
NC
S
P(OR)2
(168)
(169)
Sulfur functionality can be introduced into phosphorus!containing compounds by nucleophilic displacement of chloride by thiols\ in a manner analogous to that in which "047# is formed from "046# ð77SC0500Ł[ More commonly\ sulfur is introduced as an electrophile[ Sulfenylation of phosphorus stabilised carbanions is a useful general method for the formation of compounds containing two sulfurs and phosphorus[ A further sulfur substituent can be introduced into a species containing one sulfur and one phosphorus substituent\ as in sulfenylation of the ylide Ph2P1CHSPh ð89TL3248Ł and of the phosphonate Ph1POCH1SPh ð66JCS"P0#1152\ 79S016Ł[ Alternatively\ both sulfur substituents can be introduced by sequential sulfenylation^ two examples are shown in Scheme 15 ð77S451\ 81SC0248Ł\ and other examples are known ð74JCS"P0#1474Ł[ i, LDA, THF ii, (MeS)2
NPh PPh2
NPh PPh2
i, LDA, THF ii, (MeS)2
(EtO)2P
Al2O3-KF, MeSSO2Me microwave
CO2Et
PPh2 MeS
SMe O
NPh
SMe
O (EtO)2P
CO2Et
MeS
SMe
Scheme 26
S!Methyl "diisopropoxyphosphonyl#dithioformate "069# reacts with carbon nucleophiles on sulfur to give S!alkylated products such as "060# "Equation "05## ð76JCS"P0#070\ 78TL2304Ł[ A similar attack on sulfur occurs with thiols ð81JOC3496Ł[ O
O (PriO)
2P
(PriO)
SMe
SMe O
2P
(EtO)2POCF2Li
S
S
(16)
P(OEt)2
F F (171)
(170)
Trialkylphosphines add to carbon disul_de to give zwitterionic adducts "061#[ These will undergo cycloaddition with acetylenedicarboxylic esters leading to the ylides "062# ð64CC859\ 65BCJ0885\ 68JOC829\ 80JOC0705Ł[ Benzyl thiol reacts with the bisisothiocyanate "063# to give the symmetrical product "064# arising from double cyclisation ð81HAC004Ł[ Similar compounds are obtained by the treatment of compound "065# with acid chlorides with aluminum trichloride catalysis[ The product "066# is a result of a carbon for phosphorus replacement[ Oxidation with hydrogen peroxide gives the phosphine oxide "067# "Scheme 16# ð89JCS"P0#08Ł[ Preformed diethyl a\a!bis"methylthio#phosphonate undergoes lithiation and subsequent 0\1! addition on to a\b!unsaturated aldehydes and ketones to give the alcohols "068# "Equation "06## ð81T7586Ł[ The phosphine sul_de "079# can be methylated with methyl tri~ate to give the S!methyl! phosphonium salt\ which on reaction with HMPA is reduced to the corresponding phosphine ð80TL6218Ł[ R2 O (EtO)2P
SMe Li SMe
+
R1
COR1
O R1
(EtO)2P MeS
OH SMe
(179)
(17)
011
Chalco`en and Any Other Heteroatoms +
PR13
S
+
R2O2C
R13P
R13P + CS2
–
CO2R2
S–
S R2O2C
(172)
Ph
CO2R2 (173)
O N P N
O SCN P NCS
S
SH
S
S
CHCl2 (174)
(175)
RCOCl, AlCl3
P S P S
O
H2O2
P S
P
S
S
(176)
S R (178)
R (177) Scheme 27
S
S
PPh2 S (180)
"iii# Functions bearin` one sulfur\ one phosphorus and one nitro`en substituent This functionality can be produced by reaction of suitably substituted carbanions with elec! trophilic sulfur reagents[ Compounds "070# ð81SC1270Ł and "071# ð74RTC066Ł are examples of compounds formed in this way\ by sulfenylation a! to phosphorus[ The same type of sulfenylation can be achieved starting with a haloalkane and elemental sulfur ð71TL802Ł[ A di}erent method is the addition of a nucleophilic phosphorus reagent to a thioimidate\ as in the conversion of the thioimidate "072# into "073# with sodium diethyl phosphite ð67JCR"S#30Ł[ The same product can be formed by addition of methylmagnesium iodide to the C1N bond of compound "074# "Scheme 17# ð64S674Ł[ O Ph
SMe N H
O (EtO)2P
PPh2 O
SR (182)
(181)
NCO2Et MeS
(EtO)2PO–Na+
O (EtO)2P
O NHCO2Et SMe
(183)
NC
(184)
MeMgI
(EtO)2P NCO2Et MeS (185)
Scheme 28
Diazomethane undergoes cycloaddition with the vinyl sulfone "075# yielding initially the dihy! dropyrazole "076# "Equation "07## ð74CL0988Ł[
012
Chalco`en and Group 04 O
O CH2N2
(EtO)2P
(EtO)2P
N N (18)
Ph MeO2S
SO2Me
Ph
(187)
(186)
"iv# Functions bearin` one sulfur and two phosphorus substituents The sulfenylation of carbanions a! to phosphorus is used to produce this type of compound ð79S016\ 89H"29#744Ł^ an example is the bis"phosphonate# "077# ð79S016Ł[ Trialkyl phosphites react with thiophosgene to give compounds containing this functionality "Scheme 18# ð77PS"39#0Ł[ A related reaction has also been reported ð89TL0040Ł[ O
O
(EtO)2P
P(OEt)2 SPh (188)
O
O P+(OR)3 Cl–
(RO)2P (RO)3P + CSCl2
S
O
(RO)2P
∆
P(OR)2 S
P(OR)2
O Scheme 29
P(OR)2 O
5[93[0[1[2 Functions bearing selenium and P\ As\ Sb or Bi "i# Functions bearin` one selenium\ one sulfur and one phosphorus substituent Selenylation of the anion of the a!sul_nylphosphonate "078# can be accomplished with phenyl! selenyl bromide "Equation "08## ð81TA0404Ł[ Similar selenylations can be achieved using selenium and iodomethane ð70TL2986Ł[ Phenylselenyl chloride also adds to the phosponium ylide Ph2P1 CHSPh ð72CB0844Ł[ Alternatively\ a compound with this functionality is formed by addition of trimethyl phosphite to the heterocyclic cation "089# ð89CC369\ 80JCS"P0#046Ł[ i, BunLi ii, PhSeBr
(EtO)2P O
S
PhSe
(19)
(EtO)2P
S
O
O
O (189) S+ Se (190)
"ii# Functions bearin` two selenium and one phosphorus substituent Reaction of diethyl methylphosphonate with LDA and then with phenylselenyl bromide gives the diselenated product ð81TL4264Ł[ In a similar fashion\ double selenation of the ylide Ph2P1CHMe has been observed ð68CB244Ł[ Trialkyl phosphites add to 0\2!diselenonium cations in a manner
013
Chalco`en and Any Other Heteroatoms
analogous to that with the cation "089# ð77HCA0131\ 81TA0404Ł^ a similar reaction is known with tributylphosphine ð73TL3116Ł[ The a!diazophosphonate "081# undergoes insertion into the diseleno heterocycle "080# in the presence of boron tri~uoride etherate "Equation "19## ð80TL3078Ł[ Se Se
N2
+
Se
BF3•Et2O
P(OMe)2
P(OMe)2
O (192)
(191)
Se
(20)
O
5[93[1 FUNCTIONS CONTAINING CHALCOGEN AND A METALLOID AND POSSIBLY A GROUP 04 ELEMENT 5[93[1[0 Functions Bearing Chalcogen and Boron No compounds in this category have been noted[ It is possible\ however\ that the anion which can be formed from a!phenylthioalkylboronic esters "082# ð67JA0214Ł could react with a range of sulfur\ selenium and phosphorus electrophiles[ R1
O B O
PhS
(193)
5[93[1[1 Functions Bearing Chalcogen and Silicon 5[93[1[1[0 Functions bearing oxygen and silicon "i# Functions bearin` two oxy`en and one silicon substituent Silyl ketals such as "083# are produced from the reaction of alkyl benzoates with TMS!Cl\ magnesium and HMPA ð60JOM"15#072\ 68JOC319Ł[ Silylated hemiketals are also accessible from the TMS!Cl\ magnesium and HMPA reagent combination ð60JOM"15#072Ł[ Acetals with a su.ciently acidic a!hydrogen atom can be deprotonated and silylated using TMS!Cl ð80T2060Ł[ An alternative approach is to form acetals from silyl ketones such as "084# "Scheme 29# ð58CJC3236\ 79TL0246\ 89JA0851Ł[ O
TMS-Cl, Mg, HMPA
OMe
Ph
O Ph
HO
OH
, BF3, Et2O
SiPh3 (195)
Ph
OMe O-TMS TMS (194) O
O
Ph
SiPh3
Scheme 30
Oxidation of compounds containing a vinylsilane moiety provides another route into functions bearing two oxygens and a silicon[ Treatment of a highly strained 0!trimethylsilylcyclopropene derivative "085# with excess mcpba leads to the formation of the epoxide "086# ð75TL4032Ł[ Oxidation of the compound "087# containing two furan rings with singlet oxygen selectively gives the product "088# resulting from cycloaddition to the silylated ring ð89TL6190Ł[ Two other methods starting from vinylsilanes are the rearrangement of the trimethylsilylallene "199# to the dihydrofuran "190# ð71TL298Ł and the addition of dichlorocarbene to 1!trimethylsilyldihydrofuran "191# and sub! sequent reaction with methanol ð73JOM"154#126Ł[ 0!Ethoxy!0!trimethylsilylallene also undergoes
014
Chalco`en and a Metalloid
cycloaddition with enones at the substituted double bond to give products containing this func! tionality "Scheme 20# ð80CB0314Ł[ TMS
mcpba
O TMS
OCHO
TMS
OCHO (197)
(196) 1O 2
O
O
O
O
O TMS
O
TMS (198)
(199) TMS
HO
OMe
•
MeO O
TMS (200)
(201) Cl
Cl TMS
:CCl2
Cl
O
O
(202)
MeOH
OMe O
TMS
TMS
Scheme 31
The disilene "192# and methylfuran!1!carboxylate give a ð1¦1Ł cycloaddition product "193#[ This reaction is particular to the methyl ester\ higher homologues failing to react "Equation "10## ð80OM2355Ł[ Ar
Ar O Si Ar
Ar
+
Si Si Ar
Ar
O
CO2Me
(203)
Si
O
MeO Ar (204)
(21)
Ar
"ii# Functions bearin` one oxy`en\ one phosphorus and one silicon substituent Deprotonation of the a!"trimethylsilyloxy#phosphonate ester "194# with LDA and quenching with TMS!Cl gives the silylated adduct "195# ð70CC858Ł[ Quenching of the lithiated intermediate generated from the a!substituted!a!trimethylsilyloxy phosphonate "196# a}ords some of the alcohol "197# by Wittig rearrangement in addition to recovered starting material ð68TL3364\ 71BCJ113Ł[ The a! diazophosphonamide "198# reacts with aldehydes to yield epoxides "109# "Scheme 21# ð78AG506\ 80NJC282Ł[
"iii# Functions bearin` one oxy`en and two silicon substituents Two silicons can be introduced into a variety of carboxylic acid derivatives by reaction with TMS!Cl and Group 0 or Group 1 metals "Equation "11##[ The addition of HMPA and the use of coordinating solvents often leads to improved yields[ Thus\ primary amides react in the presence of lithium ð68JOM"066#026Ł^ carboxylic acids ð65TL0480Ł\ esters ð67BCJ1280Ł and silyl ketones ð65TL0480Ł utilise sodium while silyl ketones ð78JOC4502Ł and acid chlorides ð61JOM"28#C38Ł are converted with the addition of magnesium[ Other reactions of this type which have been described include the addition of triphenylsilyllithium to ethyl formate ð57CJC1008Ł and the interaction of methyl benzoate with aluminum chloride and tris"trimethylsilyl#aluminum ð70AG"E#470Ł[
015
Chalco`en and Any Other Heteroatoms O TMS-O
O
i, LDA ii, TMS-Cl
P(OEt)2
TMS-O
P(OEt)2
TMS (206)
(205) O TMS-O
O i, LDA ii, H2O
P(OEt)2
TMS Ph
Ph (207)
P(OEt)2 OH
(208)
O
O
(PriNH)2P
TMS
(PriNH)2P
heat, RCHO
N2
TMS
R (210)
(209)
O
Scheme 32
O
TMS-Cl, M
R
X
R
TMS O-TMS TMS
(22)
Triphenylsilylsilyloxirane can be deprotonated with n!butyl lithium at the substituted carbon atom[ Quenching of the intermediate with TMS!Cl a}ords the bis"silyl#oxirane "100#[ 0\0!Bis"tri! methylsilyl#ethene undergoes 0\2!dipolar cycloaddition with benzonitrile oxide giving the dihy! droisoxazole "101# ð72JOC2078Ł[ O
N
Ph
O
Ph3Si TMS (211)
TMS TMS (212)
5[93[1[1[1 Functions bearing sulfur and silicon "i# Functions bearin` one sulfur\ one oxy`en and one silicon substituent The acidity of the proton located on a methylene or methyne unit between a sulfur and an oxygen facilitates deprotonation and subsequent quenching with activated silyl compounds[ Prop! 0!enyloxathiane "102#\ on treatment with s!butyllithium and TMS!Cl gives the a!silylated product "103# "Equation "12## ð81T1490Ł[ The acidity of the proton is increased when the sulfur atom is present at its highest oxidation state\ i[e[\ as a sulfone\ when n!butyllithium will su.ce to cause reaction ð68TL2264\ 77CC534\ 89TL0766\ 80JCS"P0#786Ł[ i, BusLi ii, TMS-Cl
S
S
O (213)
(23) O
TMS (214)
Once formed\ these silylated compounds can undergo further deprotonation and alkylation[ Thus\ 1!trimethylsilyl!0\2!oxathiane "104# is methylated after treatment with s!butyllithium "Equation "13## ð74JOC551Ł[ Other alkylations of this type are known ð74TL1564\ 76JAP5150876\ 76TL1036\ 78JOC4992\ 81JAP3038042Ł[
016
Chalco`en and a Metalloid TMS O
TMS i, BusLi ii, MeI
S
O
S (24)
(215)
Cycloadditions o}er a further route into this trisubstituted functionality[ Phenyl trimethylsilyl thioketone\ which can be generated by the rearrangement of 1!phenyl!1!silylthiirane\ ð56JA320Ł will react with nitrile oxides ð70CC711\ 89H"20#36Ł\ a!nitrosostyrene ð74TL1020\ 76JCS"P0#1536Ł and silyl enones ð80TL1860Ł to a}ord cyclic products "Scheme 22#[ N O PhCNO
Ph
O
S
S
Ph
TMS Ph
Ph
S
Ph TMS
N O
N
Ph
Ph
TMS
TMS
S TMS
S
O
Ph TMS
O
TMS
Scheme 33
"ii# Functions bearin` two sulfur and one silicon substituent Bis"alkylthio#methanes such as "105#\ on treatment with base and on subsequent addition of a silylating agent o}er facile access to both tertiary "106# ð64ZAAC"307#197\ 89CL0300\ 89JOM"277#36\ 80TL5790Ł and quaternary ð66JOC0556\ 74S587\ 75HCA33\ 75JCS"P0#084\ 77ZOB0955Ł bis"alkyl! thio#trialkylsilylmethanes "Equation "14##[ The preferred reagent for deprotonation is n!butyl! lithium\ and trialkylsilyl chlorides are used most often to quench the lithiated intermediate[ These conditions are general enough to allow silylation at hindered positions ð75HCA33Ł[ The presence of TMEDA can lead to higher yields ð77ZOB0955Ł[ Dichlorodimethylsilane has been demonstrated to undergo double substitution of chloride by 1!lithio!1!methyl!0\2!dithiane ð56JA323Ł[ TMS
i, BuLi ii, TMS-Cl
EtS
SEt
EtS
(216)
SEt
(25)
(217)
With 1!allyl substituted 0\2!dithianes\ the lithiated intermediate conceivably could be silylated at either the a! or the g!position of the allyl substitutent[ It is found that silylation usually occurs mainly at the a!position\ even when this leads to the more sterically congested of the two possible products "Scheme 23# ð68TL0716\ 79JCS"P0#1567\ 75HCA0267\ 76JOC744Ł[ In the case of the dithiane derivatives "107#\ deprotonation by LDA and silylation takes place a! to the ring for R Me but at both the a! and the g!positions for R Ph ð77JCS"P0#2256Ł[ S
Ph
i, BuLi ii, TMS-Cl
Ph
S
TMS S
Scheme 34
S S
SR (218)
S
017
Chalco`en and Any Other Heteroatoms
Products which contain sulfur in a higher oxidation state can be accessed by the use of starting materials at the required level of oxidation[ Thus\ the sulfone "108# reacts with trialkylsilyl per! ~uorobutanesulfonates and two equivalents of n!butyllithium to give the products "119# "Equation "15## ð82CB426Ł[ Alternatively\ oxidation can be performed on the silylated compound ð65JOC2864Ł[ O
O
O S
O S
C4F9SO3SiR3
R3Si
(26)
SiR3
S
S
O O (219)
O O (220)
There are many examples of the lithiation of bis"alkylthio#trimethylsilylmethanes and reaction with electrophiles to generate quaternary products "Equation "16##[ Alkylations have been performed with iodoalkanes ð79JA5050\ 80TL1710Ł with the optional addition of HMPA ð73HCA0623Ł[ The sulfone "119^ R Me# is methylated with methyl per~uorobutanesulfonate after deprotonation with two equivalents of n!butyllithium ð80CB0794Ł[ Acetylation of 1!trimethylsilyl!0\2!dithiane has been accomplished by the use of acetyl chloride ð62JCS"P0#1161Ł[ Michael addition of lithiated bis"phen! ylthio#! ð78JOC0189Ł and bis"methylthio#! ð66CB730Ł trimethylsilylmethanes occurs with cyclo! pentenone^ the bis"methylthio# intermediate also adds 0\3! to t!butyl cinnamate ð74TL2920Ł[ 1!Lithio!1!trimethylsilyl!0\2!dithiane undergoes 0\1!addition to cyclohex!1!enone but addition of HMPA to the reaction mixture promotes 0\3!addition ð68CC099Ł[ TMS
Li
R1S
SR1
R2
TMS
R2X
R1S
(27)
SR1
"iii# Functions bearin` one sulfur\ one nitro`en and one silicon substituent The examples of compounds falling into this class in the literature are formed exclusively by cycloaddition[ The thioketone "110# reacts with diazomethane to give the dihydro!0\2\3!thiadiazole "111# ð80MI 593!90Ł[ A dihydro!0\2\3!thiadiazole "112# is obtained from the treatment of thioketone "113# with the hydrazonyl chloride "114# in the presence of triethylamine ð89H"20#36Ł[ The tri! methylsilylallene "115# undergoes a ð1¦1Ł cycloaddition with chlorosulfonyl isocyanate leading to the b!lactam "116# "Scheme 24# ð74TL4990Ł[
But
TMS
CH2N2
N N
But
TMS S (222)
S (221)
Ph Ph
TMS
N N
Ph
PhCH(Cl)=NNHPh (225), Et3N
S
TMS
S (224)
(223) SAr •
SAr
i, CSI ii, Na2SO3
TMS
TMS
NH O
(226) (Ar = 4-ClC6H4)
(227) Scheme 35
Ph
018
Chalco`en and a Metalloid "iv# Functions bearin` one sulfur\ one phosphorus and one silicon substituent
Pairwise combinations of sulfur\ phosphorus and silicon attached to the same carbon atom will all activate the carbon atom towards anion formation or radical halogenation[ The introduction of the remaining element as an electrophile or nucleophile\ as appropriate\ will allow the formation of the complete functional group[ Thus\ deprotonation of diethyl "methylthio#methylphosphonate or diethyl "trimethylsilyl#methylphosphonate with n!butyllithium and quenching with TMS!Cl or with dimethyl disul_de\ respectively\ leads to the same trisubstituted product "Scheme 25#[ The same compound can be prepared by the radical bromination of trimethylsilyl"methylthio#methane and subsequent Arbuzov reaction with triethyl phosphite[ Of these reactions\ the silylation confers the best yield ð78S090Ł[ 0\2!Dipolar cycloaddition of nitrile sul_des to the silylated phosphaalkene "117# and subsequent elimination of a nitrile leads to the formation of the three!membered ring species "118# "Scheme 26# ð78TL3490Ł[ An alternative route to this ring system has been described ð76TL5010Ł[ O (EtO)2P
i, BunLi; ii, TMS-Cl
SMe
O
O (EtO)2P
i, BunLi; ii, Me2S2
TMS
(EtO)2P
SMe TMS
i, NBS
TMS
SMe ii, P(OEt)3
Scheme 36 Ph
TMS P
+
R
N S
N S
Ph
–
R Cl
P
Ph
– RCN
TMS Cl
Cl
(228)
TMS
P
S
(229) Scheme 37
"v# Functions bearin` one sulfur and two silicon substituents Treatment of phenylthio"trimethylsilyl#methane sequentially with n!butyllithium and TMS!Cl gives phenylthiobis"trimethylsilyl#methane[ This can be alkylated by the addition of further n! butyllithium and an alkyl halide ð80T504Ł or it can be oxidised to the sulfone with peroxybenzoic acid ð73JOC4976Ł "Scheme 27#[ Examples of double silylation by TMS!Cl of a carbanion adjacent to a sulfone function are also known ð78LA864Ł[ More bulky silylating agents such as triethylsilyl chloride give selective monosilylation ð78TL1762Ł[ i, BunLi ii, BrC3H6Ph
PhS
TMS
PhS TMS
i, BunLi ii, TMS-Cl
PhS
TMS TMS
Ph TMS
PhSO2
PhCO3H
TMS TMS
Scheme 38
The cycloaddition of the thiocarbonyl ylide "129# to dipolarophiles such as methyl acrylate "Equation 17# ð76CPB0623Ł and acrylonitrile ð75H"13#0460Ł gives bis"trimethylsilyl# substituted tetrahydrothiophenes[ The alkene "120# undergoes thermal isomerisation to the bis"trimethylsilyl# thiirane "121# "Equation "18## ð76CL1066Ł[ TMS
X
X +
S
–
TMS
CH2
S
TMS (230)
X TMS
+
TMS (X = CN, CO2Me)
S
TMS
(28)
029
Chalco`en and Any Other Heteroatoms S
S ∆
Ph
TMS Ph
TMS
TMS
Ph
TMS
(231)
(29)
Ph (232)
5[93[1[1[2 Functions bearing selenium and silicon "i# Functions bearin` one selenium\ one sulfur and one silicon substituent Deprotonation of methyl phenyl sulfone with LDA and reaction of the carbanion with TBDMS! Cl gives the silylated product[ Addition of a further equivalent of LDA and conversion to the cuprate can be followed by reaction with selenocyanogen to give the selenocyanate "122# ð76TL4010\ 77JA7560Ł[ 0!Benzenesulfonyl!0!trimethylsilylalkenes such as "123# undergo Michael addition by alkyllithium reagents and the resultant lithiated species can be quenched with phenylselenyl chloride "Scheme 28# ð70TL3176\ 73TL1910Ł[ PhSO2Me
i, LDA ii, TBDMS-Cl
PhSO2
SiMe2But
i, LDA ii, CuCN
PhSO2
iii, (SeCN)2
SiMe2But SeCN (233)
TMS
PhSe i, MeLi ii, PhSeCl
PhSO2
TMS
PhSO2
O
O OMe
OMe
(234) Scheme 39
"ii# Functions bearin` one selenium and two silicon substituents Reaction of a!trimethylsilyl!a!phenylselenyltoluene "124# with LDA and TMS!Cl gives the product "125# bearing two trimethylsilyl groups "Equation "29## ð66JOC0662Ł[ PhSe
Ph
i, LDA ii, TMS-Cl
TMS SePh TMS
Ph
TMS (235)
(30)
(236)
5[93[1[2 Functions Bearing Chalcogen and Germanium 5[93[1[2[0 Functions bearing oxygen and germanium "i# Functions bearin` two oxy`en and one `ermanium substituent Only one example of this functional group has been reported[ Reaction of the ketal "126# with trimethylgermyl chloride gives the substitution product "127# "Equation "20## ð72CC128\ 72T2962Ł[ O
O Li
TMS
O Me3GeCl
GeMe3 TMS
(237)
O
(238)
(31)
020
Chalco`en and a Metalloid "ii# Functions bearin` one oxy`en\ one nitro`en and one `ermanium substituent
One class of compound has been noted with this grouping[ Treatment of dimethylamides with triethylgermyllithium gives the O!lithiated intermediates "128# resulting from addition to the car! bonyl group[ On workup\ these intermediates are converted into the ketones "139# "Scheme 39# ð72JOM"137#40\ 77JOM"230#182\ 77JOM"237#206Ł[ O R
Et3GeLi
NMe2
LiO
GeEt3
R
NMe2
O R
(239)
GeEt3 (240)
Scheme 40
"iii# Functions bearin` one oxy`en\ one phosphorus and one `ermanium substituent Addition of dimethyl"trimethylgermyl#phosphine to phenyl trimethylsilyl ketone generates the O! silylylated product "131#[ This is believed to be obtained via the O!germyl isomer "130# "Scheme 30# ð66JOM"030#24Ł[ O Me3GePMe2
+
Ph Ph
TMS
PMe2 OGeMe3 TMS
Ph
(241)
PMe2 GeMe3 O-TMS (242)
Scheme 41
"iv# Functions bearin` one oxy`en\ one `ermanium and one silicon substituent Treatment of phenyl triethylgermyl ketone "132# with triethylsilyllithium yields the alcohol "133# ð77MI 593!90Ł[ O!Alkylated functions such as "134# are accessible from the reaction of bromo! trialkylgermanes with lithiated trimethylsilylmethyl methyl ether[ These compounds can be further alkylated at the central carbon atom "Scheme 31# ð81SL732Ł[ O
Et3SiLi
Ph
Et3Ge (243) MeO
TMS
OH SiEt3 GeEt3
Ph
(244) i, BusLi ii, BrGeMe3
MeO
TMS GeMe3
(245) Scheme 42
"v# Functions bearin` one oxy`en and two `ermanium substituents In a reaction analogous to that shown with triethylsilyllithium\ the ketone "132# reacts with triethylgermyllithium to give bis"triethylgermyl# carbinol "135# ð76IZV1761\ 77MI 593!90Ł[ Ethyl for! mate reacts with triphenylgermyllithium to give a mixture of bis"triphenylgermyl#methanol "136# and its formate ester "137#[ The latter can be converted to the former by treatment with lithium aluminum hydride ð57CJC1008Ł[
021
Chalco`en and Any Other Heteroatoms Ph
OCHO
OH
GeEt3 OH GeEt3 (246)
GePh3
Ph3Ge
GePh3
Ph3Ge (248)
(247)
5[93[1[2[1 Functions bearing sulfur and germanium "i# Functions bearin` one sulfur\ one oxy`en and one `ermanium substituent 0\2!Oxathiane\ when reacted with s!butyllithium\ reacts with trimethylgermyl chloride to give the 1!substitution product "138# "Equation "21## ð70TL1994\ 74JOC546\ 74JOC551Ł[ S
i, BusLi ii, Me3GeCl
S GeMe3 O (249)
O
(32)
"ii# Functions bearin` two sulfur and one `ermanium substituent The reported preparations of these compounds are all the results of the formation of a carbanion between two sulfur atoms and quenching with an electrophilic germanium species[ 1!Lithio!0\2! dithiane has been reacted with triethylgermyl chloride ð57CJC1008Ł\ triethylgermyl bromide ð56JA320Ł and triphenylgermyl bromide ð56JA320Ł to give products "149#[ Quaternary systems are also access! ible starting from 1!alkylated dithianes ð56JA320Ł[ Both 0\2\4!trithiane and 0\2\4\6!tetrathiocane can be substituted in the same manner ð64ZAAC"307#197\ 65CB0128Ł[ The difunctional 0!gerana!0\0! dichloro!2!cyclopentene "140# reacts with two equivalents of 1!lithio!0\2!dithiane a}ording the quaternary germanium species "141# ð73JAP48082786Ł[ The bis"sulfone# "108# undergoes substitution at both methylene groups by trimethylgermyl per~uorobutanesulfonate ð82CB426Ł[ S S S
Ge
S
Cl
GeR3
Ge
S Cl
S (250)
(251)
(252)
"iii# Functions bearin` one sulfur and two `ermanium substituents The only example in the literature of compounds containing this grouping "142# is provided by the reaction of methyl alkanesulfonates R0CH1SO2Me with trialkylgermyl halides and sodium hexamethyldisilazide ð73ZOB0731Ł^ the reaction gives a mixture of products including "142#[
R1
GeR23 SO3Me GeR23 (253)
022
Chalco`en and a Metal 5[93[2 FUNCTIONS CONTAINING CHALCOGEN AND A METAL AND POSSIBLY A GROUP 04 ELEMENT OR A METALLOID 5[93[2[0 Functions Bearing Oxygen and a Metal 5[93[2[0[0 Functions bearing two oxygens and a metal
The 0\2!dioxane "143# reacts with n!butyllithium to generate the lithiated species "144# ð72T2962Ł[ Further reaction with trimethyltin chloride a}ords the trimethylstannyl derivative "145# "Scheme 32# ð72CC128\ 72T2962Ł[ TMS O TMS
O
BuLi
(254)
O
Me3SnCl
Li
O
O
TMS
SnMe3
O
(255)
(256)
Scheme 43
5[93[2[0[1 Functions bearing oxygen\ silicon and a metal Trimethylsilylmethyl methyl ether is lithiated at the methylene group by s!butyllithium ð78TL108Ł[ The proton at the 1!position of 1!trimethylsilyloxiranes can be removed with retention of con! _guration by n!butyl! or s!butyllithium ð77JOM"230#182\ 78JOC3931Ł[ Further reaction with trimethyltin bromide gives the trimethylstannyl derivatives "146# "Scheme 33# ð78JOC3931Ł[ O
O TMS
R H
BusLi
O TMS
R
H
H
TMS
R
Me3SnBr
H
Li
SnMe3 (257)
Scheme 44
5[93[2[0[2 Functions bearing oxygen and two metals Reaction of 1!"tributylstannyl#oxirane with n!butyllithium results in the formation of the 1!lithio! 1!"trimethylstannyl#oxirane "147# "Equation "22## ð77JOM"230#182Ł[ O
O BuLi
Bu3Sn
Bu3Sn
(33)
Li (258)
5[93[2[1 Functions Bearing Sulfur and a Metal 5[93[2[1[0 Functions bearing sulfur\ oxygen and a metal Functions bearing oxygen\ sulfur and lithium are generated as intermediates in reactions which involve their subsequent reaction with electrophiles^ examples are provided by the reactions of 0\2! oxathianes "102# and "104# discussed in Section 5[93[1[1[1[ Sulfur can be present in any of its common oxidation states[ Lithiated compounds can also act as precursors to other metalled deriva! tives[ Treatment of 1!lithio!0\2!oxathiane with trimethyllead acetate results in the formation of
023
Chalco`en and Any Other Heteroatoms
compound "148# by metal exchange ð70TL1994\ 74JOC546Ł[ Another approach to compounds with these functional groups is exempli_ed by the reaction of tributylstannyllithium with the thion! olactone "159# and subsequent alkylation with iodomethane "Scheme 34# ð76JA1493\ 89JA2585Ł[ S
MeS
S O
PbMe3
i, LiSnBu3 ii, MeI
SnBu3 O
O (259)
(260) Scheme 45
5[93[2[1[1 Functions bearing two sulfurs and a metal As with functions bearing oxygen\ sulfur and lithium\ lithiated derivatives are often used as intermediates\ generated in situ\ in the derivatisation at the carbon atom between two sulfur atoms[ A range of strong bases such as the butyllithiums\ LDA\ lithium hexamethyldisilazide "LHMDS# and lithium phenylamide can be used in aprotic solvents at low temperatures to lithiate such compounds ð67JOC3124\ 67MI 593!90\ 70JOC0401\ 71JOC0034\ 75S522\ 89MI 593!90Ł[ In the lithiation of the 0\2!dithiane derived from of 1\3!hexadienal\ reaction occurs exclusively at the 1!position ð81MI 593! 90Ł[ Lithiated dithianes "151# are also available from the reaction of the dithioketene acetal "150# with alkyllithium reagents ð58TL062Ł[ Treatment of compounds bearing three phenylthio residues attached to the same carbon atom with s!butyllithium leads to replacement of one of the heteroatoms with lithium ð73JOC594\ 74JOC2155Ł[ Exchange of trimethyltin for lithium has also been used to produce a compound with this functionality "Equation "23## ð77BCJ1036Ł[ S
S
RLi
S
S
(261)
Li
(34) R
(262)
Reaction of a dithioester with ethylmagnesium iodide results in addition to the C1S bond "Scheme 35# ð68JA3621Ł[ S
EtMgI
R R
SEt
SEt MgI SEt
Scheme 46
A variety of metallated 0\2!dithianes and related species can be prepared from the 1!lithio intermediate by metal exchange[ Thus\ the tris"isopropoxy#titanium derivative "152# can be formed by reaction with tris"isopropoxy#titanium chloride ð70HCA246Ł[ In a similar manner\ trialkyltin or triaryltin derivatives can be obtained from 1!lithio!0\2!dithianes and !0\2\4!trithianes by reaction with the appropriate trialkyltin chlorides or triaryltin chlorides ð64ZAAC"307#197\ 68PS"6#192\ 75JOM"292#078Ł[ Alternative routes to functions with two sulfur and one trialkyltin substituent are exempli_ed by the alkylation of 1!lithio!1!tributylstannyl!0\2!dithiane ð78TL04\ 89JA3441\ 81CJC1224Ł
S Ti(OPri)3 S (263)
024
Chalco`en and a Metal
and by the conjugate addition of the intermediate "153# to cyclohexenone with the option of alkylation of the generated lithium enolate "Equation "24## ð64AG26\ 66CB730Ł[ MeS MeS
O
SMe Li SnMe3 SMe (264)
RX
+
Me3Sn
R O
(35)
5[93[2[1[2 Functions bearing sulfur\ boron and a metal a!"Phenylthio#alkylboronate esters such as "154# have been demonstrated to undergo lithiation with LDA "Equation "25## ð67JA0214Ł[
O
O
LDA
B O
B O Li
SPh
(36)
SPh
(265)
5[93[2[1[3 Functions bearing sulfur\ silicon and a metal a!"Trimethylsilyl#methyl sul_des and sulfones are readily metallated at the methylene group by butyllithium ð75JCS"P0#084Ł[ Subsequent exchange reactions have been used to produce trialkyltin derivatives such as "155# ð75JCS"P0#084Ł and copper derivatives ð75JOC2872Ł[ An alternative route to lithiated species is the addition of alkyllithium reagents to vinylsilanes^ thus\ the intermediate "156# is produced from H1C1C"SPh#!TMS and methyllithium ð75JCS"P0#084Ł[ Multinuclear NMR studies have demonstrated the conformational stability of the species "157# in etherÐTHF mixtures due to ion pairing[ Addition of greater than three equivalents of HMPA causes a degree of racemisation to occur ð82AG"E#0358Ł[ SnBu3 Li PhS
TMS (266)
SPh Et TMS (267)
H PhS
Li SiMe2Ph (268)
5[93[2[1[4 Functions bearing sulfur and two metals Two tributyltin functions can be introduced on to a methylene group a! to a sulfone group by lithiation and reaction with tributyltin chloride ð81CC769Ł[
5[93[2[2 Functions Bearing Selenium and a Metal 5[93[2[2[0 Functions bearing selenium\ sulfur and a metal LDA will lithiate "phenylthio#"phenylseleno#methane ð89JA4598Ł[
5[93[2[2[1 Functions bearing two seleniums and a metal Bis"phenylseleno#methane can be lithiated with the hindered base LITMP and HMPA as a cosolvent ð68JOM"066#0Ł[ As an alternative\ reaction of tris"methylseleno#methane with n!butyl! lithium results in replacement of one methylseleno group by lithium ð68TL2264Ł[
025
Chalco`en and Any Other Heteroatoms
5[93[2[2[2 Functions bearing selenium\ phosphorus and a metal Treatment of the a!"phenylseleno#methylphosphonate "EtO#1POCH1SePh with n!butyllithium results in lithiation at the methylene group ð76S058Ł[
5[93[2[2[3 Functions bearing selenium\ silicon and a metal Lithium derivatives can be generated by hydrogenÐlithium exchange\ as in the generation of the species "158# from the corresponding allyl"phenylseleno#silane and lithium diethylamide ð64JOC1469Ł or by exchange of a phenylseleno function for lithium\ as in the generation of the intermediate "169# from "160# and n!butyllithium "Scheme 36# ð67JOM"038#C09Ł[ PhSe
LiNEt2
PhSe Li
TMS
TMS
(269) SePh SePh TMS
BuLi
(271)
SePh Li TMS (270)
Scheme 47
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
Comprehensive Organic Functional Group Transformations
6.05 Functions Containing at Least One Group 15 Element (and No Halogen or Chalcogen) DAVID P. J. PEARSON ZENECA Agrochemicals, Bracknell, UK 5[94[0 FUNCTIONS CONTAINING THREE GROUP 04 ELEMENTS 5[94[0[0 Functions Bearin` Three Nitro`en Atoms 5[94[0[0[0 0\0\0!Triaminoalkanes 5[94[0[0[1 0\0\0!Trinitroalkanes 5[94[0[0[2 Mixed nitro and other functions 5[94[0[1 Functions Bearin` Three Phosphorus Atoms 5[94[0[1[0 Introduction 5[94[0[1[1 Functions bearin` tri! or pentavalent phosphorus 5[94[0[1[2 Functions bearin` heptavalent phosphorus 5[94[0[2 Functions Bearin` Three Arsenic Atoms 5[94[0[3 Functions Bearin` Three Antimony or Bismuth Atoms 5[94[0[4 Functions Bearin` Nitro`en and Other Group 04 Elements 5[94[0[4[0 Functions bearin` two nitro`en atoms and one phosphorus atom 5[94[0[4[1 Functions bearin` two phosphorus atoms and one nitro`en atom 5[94[0[4[2 Functions bearin` nitro`en and other `roup 04 elements 5[94[1 FUNCTIONS CONTAINING GROUP 04 ELEMENTS WITH METALLOIDS 5[94[1[0 Functions Bearin` Group 04 Elements and Silicon 5[94[1[0[0 Functions bearin` nitro`en and silicon 5[94[1[0[1 Functions bearin` phosphorus and silicon 5[94[1[0[2 Functions bearin` nitro`en\ phosphorus and silicon 5[94[1[0[3 Functions bearin` arsenic\ antimony or bismuth 5[94[1[1 Functions Bearin` Group 04 Elements and Boron 5[94[1[2 Functions Bearin` Group 04 Elements and Germanium 5[94[2 FUNCTIONS CONTAINING GROUP 04 AND METAL ELEMENTS\ AND POSSIBLY A METALLOID
026 026 026 032 040 040 040 040 043 044 045 045 045 046 050 051 051 051 052 057 057 058 058 069
5[94[0 FUNCTIONS CONTAINING THREE GROUP 04 ELEMENTS 5[94[0[0 Functions Bearing Three Nitrogen Atoms 5[94[0[0[0 0\0\0!Triaminoalkanes "i# Introduction Methods for the formation of compounds of general structure "0#\ commonly known as ortho! amides\ have been reviewed\ most recently bySimchen\ who has written two accounts ðB!63MI 594!91Ł 026
At Least One Group 04 Element
027
and ð74HOU"E4#2Ł\ but also by deWolfe ðB!69MI 594!92Ł and Kantlehner ðB!68MI 594!90Ł[ Each of these reviews is part of a more general treatment of ortho!acid derivatives but gives extensive references to their preparation[ R2
N
R1
R3 R4 N
R7
N
R5 R6
(1)
As expected\ compounds of this type are moderate to strong bases "unless the nitrogen atoms are acylated# and dissociate to a signi_cant degree in solution as evidenced by the conductivity measurements of Bredereck ð58MI 594!90Ł "quoted in ðB!68MI 594!90Ł#[ This gives rise to their pro! pensity for elimination\ displacement and disproportionation reactions\ as shown in Scheme 0 ð57CB40Ł\ and explains why examples from carboxylic acids higher than formic are relatively rare\ why the amines involved are generally fully substituted and why the most common structural type has three identically substituted nitrogen atoms[ R2
N
R4
R1
N
N+
R1
N
R7 R2
R2
R3
N
R5
R5
R6
N
–NR6R7
R3
R4 R4
R3 R4
N
R1
N R1 R5 N R6 R7
R7
N
R5
+ HNR2R3
R6
Scheme 1
This functional group occurs in some natural products\ e[g[\ oxaline "1# ð65T1514\ 79CPB1876Ł and dibromoagelaspongin "2# ð78T2376Ł[ Br
OMe
Br O N MeO
H N
HN
N
N
HN
N H
O (2)
N
NH
N
O
HO (3)
"ii# Preparation "a# From amidinium salts[ Formamidinium salts are reported by a number of authors to undergo reaction with secondary amines or their metal salts "Scheme 1#[ For example\ the sodium salts of N!methylanilines react with a salt "3# to give the ortho!amides "4# in modest yield ð51JOC2553Ł[ Lithium dialkylamides have been similarly used ð55AG"E#021Ł and this method was applied to the preparation of unsymmetrical examples such as "5# ð57CB0774Ł[ Potassium t!butoxide has been employed as the base in a similar synthesis ð57CB2947Ł^ in this instance the reaction may occur by the initial addition of the alkoxide moiety[ The unusual displacement of cyanide in Structure "6# is presumed to occur via the intermediacy of an amidinium salt "7# ð68S231Ł[ "b# From other amide salts[ The Vilsmeier reagent "8# reacts with the potassium salts of saccharin and phthalimide to give the unsymmetrically substituted adducts "09# ð50CB2098Ł[ Bredereck et al[ report the alkylation of N\N!diethylformamide "00# and its subsequent reaction with diethylamine to give "01# in low yield ð57CB2947Ł[ In previous studies by the same group triformamidomethane "03# was constructed from formamide via similar intermediates "02# "Scheme 2# and a comparison
Three Group 04 Elements Ar Me
N
Ar
+
N
028
ArNHMe, NaH
Me I–
Me
Ar = Ph 44%
(4)
Ar
Ar
N
N N
Me
Me
Ar
(5) Me Me Me Me
N
LiNMe2, Et2O –20 °C
Me
+
N
N
Me Me
N
N
Me
Me
63%
Me Cl–
LiNEt2, Et2O
Et
42%
Me
Et
N
Me
N
N
Me Me (6)
Me
Me
Me
N
N
Me Me
Me Me
N
Me
+
N
N (7)
LiNMe2
Me
–CN
Me
73%
N
Me Me
N
N
Me
Me
(8) Scheme 2
was made of various alkylating and acylating agents ð48CB218Ł[ When dialkyl sulfates were used the yield increased with the bulk of the alkyl group\ perhaps re~ecting the ease of the subsequent displacement step[ O
O
Me
NK
+
Cl
X
N
X
CHCl3, 20 °C
+
Me
Cl–
X = CO, 46% X = SO2, 24%
(9)
X
N
N O
N
Me
Me (10)
Et
Et O
N
Me2SO4
Me
Et
O
N
Et2NH
+
MeSO4–
Et
Et
N
Et
Et
Et
(12) H
NH2
Et N
20 °C
(11)
O
Et N
Me2SO4
Me
O
N
+
H
MeSO4–
HCONH2
O
H
H
N
N N
36%
O
H
O (13)
(14)
Scheme 3
"c# From `uanidines and their salts[ Weingarten ð57T1656Ł described the displacement of a single dimethylamino group from the tetramine "04# by heating it with phenylacetylene[ In the early 0889s\ Kantlehner et al[ used the sodium salt of alkyne to achieve a similar reaction with hexa! methylguanidinium chloride] the monoadduct "05# giving rise to a proportion of the interesting 1 ] 0 adduct "06# on distillation ð89CZ065Ł[ This latter material could be more conveniently prepared
At Least One Group 04 Element
039
directly by bubbling alkyne through a mixture of the other reagents[ The reaction of the same guanidinium salt with phenyllithium gave a reasonable yield of the triamine "07# ð60JOC1774Ł[ Kantlehner et al[ have also published a route to triaminomethanes "08# by mixed hydride reduction of guanidinium salts ð72S894Ł^ in this case the yield steadily declines with the increasing size of substituents on nitrogen\ perhaps re~ecting the stability of the products[ The alkyltitanium complex "19# has been found to insert into tetramethylguanidine "10# to give the cyclic triamine complex "11# in very high yield "Scheme 3# ð77BCJ060Ł[
Ph
C(NMe2)4 88%
(15)
Ph
NMe2 NMe2 NMe2 (18)
NMe2 NMe2 NMe2
heat
+
Ph
PhLi, Et2O
Me2N
NMe2 + NMe
52%
2
NMe2 NMe2 NMe2 (16)
HC CNa , THF 57%
Cl–
NaH,HC CH
∆, distil 20%
76%
NMe2 NMe2 NMe2
Me2N Me2N Me2N (17) R2 N
NR2 + NR
2
NR2
NaH2[Al(OCH2CH2OMe)2]
Cl–
NR2
R2 N
33–55 %
(19) Me2N
Ph
+
Cp2Ti Ph (20)
Me2N
NMe2 NH (21)
NMe2
HN 92%
Cp2Ti
Ph Ph (22)
Scheme 4
"d# From ortho!acid derivatives[ The _rst reported synthesis of this type came from Bredereck et al[ who prepared triformamidomethane "03# by treating triethyl ortho!formate with formamide in the presence of an acid catalyst "Scheme 4# ð48CB218Ł[ Follow!up studies were made in which the nature of the amide was varied and\ by controlling the stoichiometry of the reaction together with the use of toluene as solvent\ the yields were signi_cantly improved ð59CB0287\ 52CB0494Ł[ The formyl groups in "03# could be exchanged for other acyl derivatives to give "12# by reaction with an appropriate acid anhydride ð59CB0287Ł[ Urethane has been used in this context with high yields of the tricarbamate "13# reported ð56ZOR0638Ł[ Triethyl ortho!formate will also react with N!methylaniline to give the product "4# "Scheme 5# in moderate yield ð51JOC2553Ł[ Triethoxyacetonitrile "14# reacts with pyrrolidine among other amines to give the unusual nitrile "15# ð68GEP1713917Ł[ Heating diaminoalkoxymethanes of type "16# gives rise to disproportionation to amide acetals "17# and triaminomethanes "08# "Scheme 6# ð57CB40Ł[ Dithioacetals such as "29# react with suc! cinimide "18# to give the substitution products "20# ð54IZV1068Ł^ phthalimide behaves similarly[ Weisman et al[ synthesised the interesting tricyclic examples "23# by reaction of formamide or acetamide acetal "21# with macrocyclic triamines "22# ð70TL3254Ł[ They found that acetals such as "21# were preferable to simple ortho!esters[ Triazaadamantane "25# was made by condensation of triethyl orthoformate with cyclohexanetriamine "24# "Scheme 7# ð62CB1412Ł[ "e# From alkyl halides[ Clemens et al[ prepared triamines "4# by treating the sodium salts of N! alkylanilines with trihalomethanes ð51JOC2553Ł^ for this conversion di~uorochloromethane was better than either chloroform or dichloro~uoromethane[ This reaction may well proceed through a carbene intermediate and in support of this the pyrolysis of sodium trichloroacetate in the presence of such anilines gave "4# in modest yields "Scheme 8#[ Similar chemistry has been successful using a
Three Group 04 Elements
030
O HN
HCONH2, H+ 32%
EtO
R
O H N
HN
(RCO)2O, ∆
HN
O
NH
O
O
OEt
H N
R O
R
(14)
(23)
OEt OEt
O
H N
HN
H2NCO2Et
OEt
90%
NH
O
O
OEt (24) Scheme 5
EtO
OEt
PhNHMe, ∆
Me
Ph
Ph
N
N
57%
OEt
Me
N
Me
Ph
(5)
OEt OEt OEt
N
N
Et2O, ∆
+
N N H
N
57%
N
(25) (26) Scheme 6
2
R 2N
R 2N
NR2 OR (27)
N H (29)
O
SEt
+ SEt
NR2
+ NR2
OR (28)
Me2N O
R2 N
OR
50%
(19)
O Me2N
O O
N N
(30) O (31) Scheme 7
pyrazole as the amine component ð65S687\ 68LA0345Ł although 0\1\3!triazoles ð58JCS"C#1140Ł and indazoles ð68LA0345Ł gave very poor yields[ "f# From titanium salts[ Tetrakis"dimethylamino#titanium "26# reacts with DMF in ether to give a high yield of triaminomethane "27#\ whereas the corresponding acetamide derivative gave the diaminoethylene "28# ð55JA749\ 55JOC1763Ł[ Similarly\ oxamide "39# gave the same product "27# although no yield was reported "Scheme 09# ð57JOC0135Ł[ "`# Addition to polyaminoethenes[ Tetraaminoethenes "30# react with lactams and imides to give the cyclic triamines "31# ð64CB104Ł^ this type of reaction is covered in a review of similar chemistry ð61AG"E#853Ł[ Exomethylene triazinediones "32# have been shown to combine with some substituted
At Least One Group 04 Element
031
(CH2)p MeO
R
OMe
+
NMe2
(CH2)p
NH HN H N
(CH2)n
(32)
(CH2)m
(CH2)n
(33)
N
N (CH2)m
(34) R
NHR NHR NHR
R
N
43–89%
HC(OEt)3, ∆
R N
N R
N
27–31%
(35)
(36) Scheme 8
CHClF2, NaH Ar = Ph 58%
H Ar
N
Me
Me
Cl3CCO2Na, ∆
Ar
Ar
N
N
Me
N
Me
Ar
(5)
20%
Scheme 9
(Me2NCO)2 (40) Me2NH
Me2N
NMe2
Ti(NMe2)4 (37)
NMe2 (38)
HCONMe2 Et2O 83%
NMe2 Ti(NMe2)4 + MeCONMe2
87%
(37)
NMe2 (39)
Scheme 10
hydrazines by reaction at the ring carbon giving products such as Structure "33# "Scheme 00# ð64CR"C#452Ł[ Ph Ph
Ph
N
N
+
HN
(CH2)n
N 67–91%
N
N
N
toluene, ∆
N
O
Ph Ph
(CH2)n
Ph O (42)
(41) H R O
N
N N
R
R H2NNMe2
O
O
R (43)
N NMe2 R N
N N
O
R (44) Scheme 11
"h# Heterocyclisation reactions[ In an attempt to prepare an oxazoline "35# by pyrolysis of hydroxyethylamide "34#\ Slusarczuk and Joullie obtained the tricyclic compound "36# in modest yield ð69CC358Ł[ The bis"amide# "37# is reported to extrude one molecule of benzimidazole on
Three Group 04 Elements
032
sublimation giving triamine "38# ð66JCS"P0#0051Ł\ and in a similar transformation\ the acylation of diamide "49# with chloroacetyl chloride gave the tetracycle "40# in high yield "Scheme 01# ð70JOC0460Ł[ N
F3 C O (46)
O F3C
∆
OH
N H
N
30%
(45)
CF3
N N (47)
N
N N
O
O
O
N
∆, sublime
H N
N
N
92%
N O (49)
(48)
O H 2N
O
O H N
NH2
Cl
Cl
NH
O 83%
N
Cl NH O
(50)
(51) Scheme 12
"i# Radical methods[ The dimerisation of triarylimidazoles by treatment with potassium fer! ricyanide under appropriate conditions gave the photochromic dimers "41# among other products "Scheme 02# ð55JA2714\ 60JOC1151Ł[ Treatment of acetonitrile with the N!bromosuccinimide complex "42# gave the trisubstituted acetonitrile "43# ð77ACS"B#555Ł^ other aminoacetonitrile derivatives "44# and "45# gave better yields of similar products[ "j# From other triamines[ As part of a wider study\ Katritzky et al[ have trapped the anion of tris"benzotriazolyl#methane "46# with a variety of electrophiles such as alkyl halides and alkyl chloroformates "Scheme 03# ð89S555Ł[ "k# From isocyanates[ Working independently\ two research groups have found that DMF reacts with phenyl isocyanate to give the bicyclic triamine "47# ð57JOC2817\ 57JOC2820Ł[ According to the latter report this product was also obtained from amidine "48#[ Since then a number of similar reactions have been described] among other similar substrates\ lactams ð62JOC1503Ł\ amidines ð57CB2991\ 58CB820Ł\ amidinium salts ð60LA"640#034\ 79HCA0847\ 71CB0610Ł\ tetraaminoethylenes ð60LA"637#0\ 63CB0820Ł and 0\0!diaminoethylenes ð66CR"C#210Ł have all been utilised in place of DMF "Scheme 04#[ Thiocyanates also reacted similarly ð64CB0031Ł[ The cyclic selenourea "59# has been used as a source of the carbene "50# "which can also be formulated as an amidinium ylide# ð72CB1957Ł^ this reacts with phenyl isocyanate to a}ord the product "51#[ Reduction of isocyanates in situ has been used to provide the source of the spiro carbon atom in "52# ð74CB2848Ł[
5[94[0[0[1 0\0\0!Trinitroalkanes "i# Introduction Much work has been done in this area of chemistry but the special advantages o}ered by these materials in the _eld of propellants and explosives represent a signi_cant hazard in the hands of the
At Least One Group 04 Element
033
Ar
K3Fe(CN)6
Ar
N
(52)
Bu4N+
Br N
Ar Ar
N Ar
Ar
N
N
Ar
43–95%
Ar
O
N
Ar
H N
O
O
N–
O
MeCN
O
22%
O
N
O
O N
N CN
O
O (54)
(53) O
O
N
N CN
CN
O (55)
O (56) Scheme 13
N
N
N
N N
N N N N
N N N
(57)
i, ii 58–98%
N N E N
N N N
i, BuLi, THF; ii, EX E = PhCH2, CO2Et, Bun inter alia Scheme 14
unwary[ Several reviews have been published\ the most recent being in the Patai series ðB!69MI 594! 91Ł^ others cover more general aspects of nitroalkane chemistry as well as their synthesis ð48UK373\ 52T"S#044\ 52T"S#066\ 53CRV08\ 55UK0639Ł[ The presence of three strongly electron!withdrawing nitro groups attached to a single carbon atom has a profound in~uence on the chemistry of such compounds and even though not all the nitro groups are coplanar\ they are still prone to elimination and substitution reactions as well as rendering b!heteroatoms virtually non!basic[
"ii# Preparation There are two fundamental approaches to the synthesis of such compounds] the introduction of an intact trinitromethyl group "most commonly as a nucleophile but also as a radical# and the stepwise introduction of the required nitro groups[ "a# Addition of an intact trinitromethyl `roup[ The trinitromethyl anion adds readily to Michael acceptors as shown in Equation "0#[ Such reactions are typically carried out in protic solvents and in the absence of added base which can give rise to complicating by!products[ Kaplan and Kamlet report that for addition to acrylates the optimum pH is around 2[4 ð51JOC679Ł[ Addition occurs to unsaturated ketones ð57JOC0136Ł\ aldehydes ð57JCED326Ł\ phosphonates ð67MI 594!90Ł\ oximes
Three Group 04 Elements
034 O N Ph N Ph N
96%
Ph N
53%
O
N
Me
N
Se
O
(58)
(59) Ph
O Ph
N
Ph
N
Me
Ph
140–150 °C
HCONMe2 + PhCNO
Ph
Ph
Ph O
N
N+
PhNCO
N
47%
N
N
:
–
N
Ph (60)
Ph N
N Ph
Ph
N
O
Ph Ph (62)
(61) R
O N [HRu3(CO)10(SiEt2)]N(PPh3)2, Et3SiH
RNCO
22–69%
R N R N O
N N
O R O
R (63) Scheme 15
ð79MI 594!91Ł\ lactones ð75JHC70Ł and to acrylonitrile ð60ZOR29Ł[ However\ according to Kaplan\ addition to symmetrically disubstituted Michael acceptors does not occur ðB!69MI 594!91Ł[ O2N
NO2
+ NO2
EWG
O2N O2N
NO2 (1) EWG
EWG = CO2R, CHO, COR, PO(OR)2, CHNOH, CN
A detailed study of the alkylation of the silver salt of trinitromethane has been made ð52T"S#066Ł\ and although this method worked well for simple alkyl\ allyl and benzyl groups it failed for other electrophiles such as haloacetates[ One particular complication is the occurrence of competing O! alkylation ð57IZV336\ 66IZV025Ł[ Nevertheless\ variations on this method\ including the use of other salts\ have allowed reactions to occur with diiodomethane ð60ZOR0293Ł\ 0!bromoadamantane ð65KFZ24Ł\ a!chloroamines ð70IZV1035Ł\ ferrocene derivatives ð75ZOR0282Ł\ triazolyl diazonium salts ð61KGS602Ł and a!chloroethers ð89SC2292Ł as illustrated in Scheme 05[ At the beginning of the 0889s\ a study of the phase transfer catalysed methylation of the potassium salt of trinitromethane was published ð89IZV0705Ł in which the addition of a crown ether or polythylene glycols was shown to be advantageous[ This salt has also been used to substitute the pyridinium salt "53# in modest yields ð72IZV1544\ 89TL6268Ł[ Iodotrinitromethane and tetranitromethane are methylated in dipolar aprotic solvents "see Scheme 06# either via intermediate solvent alkylated species or perhaps through preliminary homo! lytic dissociation ð69ZOR078\ 63ZOR1992Ł[ Trinitromethane is methylated by diazomethane ð69IZV837Ł[ Diazo compounds such as "54# insert into bromo! or iodotrinitromethane to give trinitro derivatives "55# ð60ZOR0015\ 66ZOR0448Ł[ Tri! and tetranitromethane react with other nitroalkanes to give trinitromethyl derivatives such as "56# ð62IZV011Ł and "57# ð56USP2205200Ł\ and\ in the presence of a silylating agent\ with "58# to give ethers of "69# "Scheme 07# ð78MI 594!90Ł[ Shechter and Cates\ Jr[ found that trinitromethane reacted with enol ethers "60# at the oxygen! bearing carbon to give "61# ð50JOC40Ł^ this reaction is also reported for enol acetates in alcoholic solvents giving products of type "62# "Scheme 08# ð58IZV1455Ł[ Trinitromethane reacts with formaldehyde to give alcohol "63# ð49JA4218\ 59JOC1958Ł[ In the
At Least One Group 04 Element
035 O2N
NO2
O2N
O2N
NO2
NO2
NO2
O2N
+
O2N
Ag
+
N
O2N
R
R2N
R
OR
O–
R N
O 2N
RX
O2N
Cl
NO2 NO2
RBr, AgO benzene
Et3N
44%
53–75%
NO2 RO
O2N
I
NO2 Ag, salt, CH2I2 Et2O
CH2Cl2/DMF 14–61%
O2N
35%
HetN2+
NO2
O2N
OR
O2N
NO2 I
O2N N N R
NO2 NO2 NO2
N H
NO2 NO2
O2N KC(NO2)3
N
N
+
F X– (64)
H2O MeCN
N
41% 7%
7% 21%
Scheme 16
X
NO2 NO2 NO2
DMSO or DMF MeI X = NO2, 64% X = I, 90%
NO2 NO2 NO2
NO2 O2N NO2 dioxan 51%
CH2N2
NO2 Br
N2
CO2Et
NO2
Br
NO2 NO2 NO2
67%
CO2Et (66)
(65) Scheme 17
NO2 NO2 NO2
Three Group 04 Elements
036
NO2 O2N
NO2
NO2 water, ∆
NO2
O
32%
O
NO2 NO2 NO2 (67)
O2N
NO2 NO2 , base NO2
NO2 NO2 NO2
NO2
(68)
NO2
O
+
TMS-I, Cl –78 °C
Cl
O2N
O2N
O
O2N
65%
NO2
O
OH
NO2
(69)
(70) Scheme 18
NO2 O2N NO2
dioxan
R
OR
OR NO2
R
50–81%
(71)
NO2 NO2 (72)
NO2 O2N
OAc
NO2 ROH, ∆ 28–76%
OR NO2 NO2 NO2 (73)
Scheme 19
presence of amines such as "64# ð51JOC0344Ł and using hydroxymethylamides "65# ð50JOC280Ł\ the Mannich reaction occurs[ In the mid 0879s\ silylaminal "66# has been shown to react with silylated trinitromethane "67# under non!aqueous conditions to give amine "68# ð74IZV1524Ł[ Similar additions to higher aldehydes and ketones are reversible "Scheme 19# ð59JOC1958Ł[ Trinitromethane has also been reported to add to preformed imines such as "79# and "70#\ in these cases in halocarbon solvents ð57IZV1268\ 58IZV1298Ł[ Polynitromethanes have been added to various substrates via a radical mechanism to provide trinitromethane derivatives[ Tetranitromethane is reported to form charge transfer complexes with electron!rich aromatics such as anthracene^ subsequent photolysis can give rise to trinitroarenes "71# "Equation "1## ð74JOC4134Ł[ Other aromatic systems can lead to products such as "72# ð75RTC167Ł and "73# ð79MI 594!90Ł[ Products such as those of direct nitration may also be formed and the exact course of the reaction can be di.cult to predict ð75RTC167Ł[ O2N
NO2 NO2
C(NO2)4 hν >500 nm, CH2Cl2
(2)
16–93%
X
X NO2 (82)
Tetranitromethane will add across alkenes such as "74# ð58ZOR1135Ł and "75# ð75RTC175Ł and in
At Least One Group 04 Element
037 O2N
NO2
CH2O
NO2
O2N
NO2 OH
O2N (74) HC(NO2)3, aq. CH2O
NH2
HO
34%
(75) H N
HO H N
HC(NO2)3, H2O
OH
O2N
H N
NO2
O2N
R
O –O
N
O-TMS
+
R
O2N (77)
NO2
O2N
+
N
O-TMS
R O2N R
NO2 (78)
76%
NO2
NO2 (79)
HC(NO2)3, CHCl3
N
NO2
N
NO2
H N
NO2 NO2
87%
O (76)
NO2
O2N
H N
NO2
N H
O2N
NO2
NO2
(80) O2N
NO2 NO2
HC(NO2)3, CCl4
N
73%
N H
(81) Scheme 20
OMe NO2 NO2
NO2
NO2
NO2 NO2
(84)
(83)
such cases light is not always required "Scheme 10#[ Insertion into a C0H bond of THF a}orded "56# ð62IZV0038Ł^ a similar reaction occured with iodotrinitromethane "Scheme 11# ð61IZV389Ł[ O2N C(NO2)4
MeO
NO2 NO2
MeO
80%
NO2
(85)
C(NO2)4
N
40%
N O2N
(86) Scheme 21
NO2
O 2N NO2
Three Group 04 Elements
C(NO2)4
+ O
35%
THF, ∆ X = H, NO2, I
NO2 O
038
NO2 NO2 (67)
30–50%
+
OR
O
X
NO2 NO2 NO2
Scheme 22
Electrolysis of salts of trinitromethane as shown in Scheme 12 leads to radicals which react with cyclic ethers ð61IZV1592Ł or with toluene ð61IZV0606Ł and other aromatic systems ð71IZV1526Ł[ M+
–
NO2 NO2 NO2
e–, toluene
NO2 NO2
e–, PhR 3–25%
e–, THF
NO2 NO2
NO2
NO2
R
O
NO2
NO2 NO2 (67)
Scheme 23
The mercury salt "76# has been shown to add across the double bonds of allyl alcohol ð51IZV161Ł\ methyl acrylate ð58IZV0734Ł and vinyltrimethylsilane "Scheme 13# ð62RZC0132Ł[ TMS
OH
NO2 NO2
R Hg
Hg(C(NO2)3)2 (87)
NO2
R O2N CO2Me
NO2 NO2
Scheme 24
Trinitroacetonitrile undergoes cycloaddition reactions with TMS azide\ diazo compounds and nitrile oxides to give trinitromethyl!substituted tetrazoles "77# ð70JHC0366Ł\ 0\1\2!triazoles "78# ð76ZOR1513\ 77ZOR533Ł and 0\1\3!oxadiazoles "89# ð75ZOR1507Ł respectively[
O2N O2N
O2N O2N
NO2
NO2 N
N N
R
N
N
N NO2
N O
N H (88)
Ar
N
NO2 NO2
R (89)
(90)
There have been many reports of the cycloaddition of trinitromethane derivatives with alkenes "Equation "2## to give products of type "80#[ Tetranitromethane has been shown to react directly with cyclohexene ð56ACS"C#0281Ł\ ethylene ð55ZOR0891Ł\ vinyl ethers ð58ZOR119Ł and butadiene ð58ZOR0202Ł[ Bromo! and iodotrinitromethane have taken part in similar reactions ð56ZOB0052\ 57IZV510\ 62ZOR158Ł[ Trinitromethane can be O!silylated ð62ZOR785Ł and the resulting adduct reacts with styrene to a}ord "81#[ O!methylation with diazomethane followed by reaction with butadiene yields "82# "Scheme 14# ð57ZOR120Ł[
At Least One Group 04 Element
049 R
XC(NO2)3
R
X
NO2
O2N
N
R
O
O
X = Br, I, NO2
R
(3)
R
R (91)
O2N TMS-Cl
O2N
TMS-O
NO2 NO2
O2N
NO2 N+
styrene
NO2
94%
O–
Ph
CH2N2
O2N MeO
O2N
NO2 N+
N O-TMS O (92)
butadiene
NO2
70%
O–
N O
OMe
(93) Scheme 25
"b# Successive nitration reactions[ The trinitromethyl group has been assembled by successive nitration from various starting materials[ For example\ trinitromethane itself can be made on a commercial scale by treatment of acetylene with concentrated nitric acid in 63) yield ð52T"S#044Ł[ Cyanoacetic acid has been converted to trinitroacetonitrile in good yield using a mixture of nitric acid and sulfur trioxide ð51T68Ł[ Nitrile oxides "83# react with dinitrogen tetroxide to give aryl derivatives "84# "Equation "3## ð89IZV0519\ 89IZV0512Ł[ Oximes have been converted to either di! ð77BCJ1816Ł or trinitromethanes ð59IZV0672\ 69KGS489Ł using nitrogen dioxide[ N2O4, CH2Cl2
+
N O–
Ar
Ar 45–79%
(94)
NO2 NO2 NO2 (95)
(4)
Dinitromethanes may be prepared as precursors to their trinitro counterparts^ Kaplan and Shechter used silver nitrate:sodium nitrite on the silver nitronates "85# ð50JA2424Ł[ Less conveniently\ chloronitromethanes can be nitrated ð53CRV08Ł and tetranitromethane treatment of nitroalkanes has also been used ð50USP1880204\ 56USP2205200Ł[ Other reagents have been used for the further nitration of dinitro analogues\ e[g[\ nitryl ~uoride "86# ð60IZV0483Ł[ Tri~uoroacetic anhydride "TFAA# and nitric acid react with dinitroalkenes such as "87# but less successfully with mononitro analogues such as "88# "Scheme 15# ð81JOC2915Ł[
+
N
O–
O– (96)
Ag+
AgNO3, NaNO2, NaOH Et2O, 0–5 °C
FNO2 (97) MeCN
MeCH(NO2)2 78%
H N
NO2
N H
NO2 (98)
89% TFAA, CH2Cl2 90% HNO3
H N
22%
N H
MeC(NO2)3 43–67%
NO2 (99) Scheme 26
H N N H
NO2 NO2 NO2
Three Group 04 Elements
040
5[94[0[0[2 Mixed nitro and other functions One nitro group in trinitroethane has been displaced by azide in DMF as shown in Scheme 16 ð73BRP1012718Ł[ The same product was obtained by electrolysis of the sodium salt of dinitroethane in dilute sodium azide ð64USP2772266Ł and other examples have been similarly prepared ð89MI 594! 90Ł[ NO2 NO2 NO2
NO2 N3 NO2
NaN3, DMF 28%
aq. NaN3, e–
NO2 NO2
Scheme 27
5[94[0[1 Functions Bearing Three Phosphorus Atoms 5[94[0[1[0 Introduction Functional groups of this type fall into two main classes] those with tri! or pentavalent phosphorus which are predominantly used as ligands in organometallic chemistry "e[g[\ ð81OM15Ł#\ and tris "phosphonato#methanes which have been used as surfactants "e[g[\ ð66USP3919980Ł#[
5[94[0[1[1 Functions bearing tri! or pentavalent phosphorus "i# From functions bearin` two phosphorus `roups The method _rst reported by Issleib and Abicht for the reaction of methylenebisphosphines with a chlorophosphine has been subsequently much utilised to prepare ligands for organometallic complexes "Scheme 17# ð69JPR345Ł[ The original workers described the reaction of lithium salts of bisphosphine "099# and its corresponding bisphosphine oxide "090# with diphenylphosphinyl chloride to form tris"phosphino#methanes in good yields[ Karsch et al[ extended the work to include alkyl substituents\ preparing methylphosphines "091# ð68AG"E#373\ 68ZN"B#0060Ł[ Grim and Walton report phosphine sul_des "092# made by the same basic method ð79PS"8#012Ł^ the paper contains no experimental details even though a report from the same group mentions the preparation of asymmetric tris"phosphino#methane "093# ð75IC1588Ł[ In this case\ the reaction was carried out on transition metal carbonyl complexes of the carbanion of bis"phosphino#methane "094# to improve the chemoselectivity ð71CC175Ł[
"ii# By further reaction of tris"phosphino#methanes Tris"phosphino#methanes have been modi_ed at phosphorus to produce a number of oxides\ sul_des and selenides in various combinations[ The _rst report was by Issleib and Abicht ð69JPR"201#345Ł who converted tris"diphenylphosphino#methane "095# into its trisul_de "096# by heating with sulfur[ This method ð71CB707Ł failed to produce the alkyl analogue "097# which could\ however\ be prepared from a bis"thiophosphinoyl#methane by the standard method "Scheme 18#[ Grim et al[ report the modi_cation of a variety of tris"phosphino#methanes] the mild oxidation of phosphine "095# to phosphine oxide "098# avoids the cleavage of one of the carbonÐphosphorus bonds which occurs under harsher conditions ð75IC1588Ł[ This method was then applied to a number of phosphine sul_des and selenides[ Red selenium was also used to convert phosphine sul_de "009# into "000# although an earlier paper mentions that carbonÐphosphorus bond cleavage occurred in similar reactions ð79PS"8#012Ł[ Grim also reports that salts of phosphines react more readily with selenium because of a reduction in steric crowding ð76PS"27#68Ł[ The functionalisation of phosphorus in metal carbonyl complexes by oxidation using either hydrogen peroxide or sulfur has been claimed although no details are given ð71CC175Ł[ The phosphine imine "001# was prepared in excellent yield by reaction of phosphine "009# with p!tolyl azide "Scheme 29# ð80CC868Ł[ Karsch et al[ describe the methylation of the lithium salt of tris"dimethylphosphino#methane
At Least One Group 04 Element
041
Li
BuLi
Ph2P
PPh2
Ph2P
86%
(100)
PPh2
Ph2PCl
PPh2
Ph2P
61%
PPh2
PPh2 Ph2P
i, BuLi ii, Ph2PCl
PPh2
R12P
Ph2P
73%
O O (101)
i, BuLi ii, R32PCl
PR22
PPh2
O
O
PR32 R12P (102)
S
i, Ph2PSCH2Li ii, Ph2PCl
S Ph2P
Li
PR22
R1, R2, R3 = Ph, Me
Ph2PCl
Ph2P
PPh2
S Ph2P
PPh2 PPh2
(103) O
S
Ph2P
PPh2
O
i, BuLi ii, Ph2PCl
S
Ph2P
PPh2 PPh2 (104)
PPh2 (CO)4M
–
PPh2
M = Cr, W, Mo
(105) Scheme 28
PPh2
S8, C6H6
Ph2P
56%
PPh2
Ph2P
Me2P
PMe2
S PPh2
S S (107)
(106) PMe2
Ph2P
Me2P
S
S8
Me2P
PMe2
i, ButLi ii, Me2PSCl 41%
Me2P S
PMe2 S
S S (108) Scheme 29
"002#] using low temperatures and ether solvents alkylation occurs at carbon to give "003# whereas in pentane with TMEDA alkylation takes place on phosphorus to a}ord the ylide "004# "Scheme 20# ð73ZN"B#0407Ł[
"iii# From phosphaalkynes Phosphaalkynes\ their oligomers and derived metal complexes have been used to prepare complex polycyclic analogues of tris"phosphino#methanes[ This chemistry has been reviewed ð77AG"E#0373\
Three Group 04 Elements PPh2
Ph2P
S
O O (109) PPh2
Se, ∆
PPh2
Ph2P
PPh2
Ph2P
81%
(106)
Se
O
Ph2P
H2O2, acetone, 0 °C
PPh2
Ph2P
042
Ph2P
>95%
S
S (111)
TolN3, ∆
PPh2
Ph2P
S
Ph2P
NTol PPh2
S S (112)
(110) Scheme 30
PMe2 PMe2 PMe2
MeI, Et2O, THF
PMe2 PMe2 PMe2
Li
–115 °C to 20 °C 65%
(114)
MeI, TMEDA, pentane
+
Me3P 80%
PMe2 –
PMe2
(113)
(115)
Scheme 31
89CRV080Ł[ Wettling et al[ report that the prolonged pyrolysis of "005# gave the tetraphosphacubane derivative "006#\ albeit in very low yield ð78AG"E#0902Ł[ Prior reaction of the alkyne to form a zirconium complex "007# greatly improves the conversion ð81AG"E#647Ł[ The phosphacubane "006# has been functionalised at a single phosphorus vertex using a number of reagents ð81AG"E#768\ 82JOC3094Ł[ The zirconium complex "007# has been treated with phosphorus trichloride to form the bicyclic compound "008# "Scheme 21# ð80AG"E#196Ł[
But But
130 °C, 65 h
But
But P P
P 8%
P
P But
(116)
(117)
Cp2ZrCl2 70% BuLi
70%
But
But P
CCl3CCl3, C6H6
Cp2Zr
P
But (118)
P
P But PCl3, hexane 110 °C
But
75%
Cl
P
P
But (119) Scheme 32
P
At Least One Group 04 Element
043
Aluminum chloride catalysed tetramerisation of the phosphaalkyne "005# yielded polycyclic derivatives such as "019# ð81AG"E#0944Ł[ Tungsten ð80CC0294Ł\ manganese ð82AG"E#0313Ł\ iron ð78AG818Ł and vanadium complexes ð76AG"E#897Ł have been converted to related polycyclic systems\ for example "010# "Scheme 22#[
But
P
P
P
i, AlCl3, CH2Cl2, 0–25 °C P ii, But
But
But
But
95%
P
P But (120)
(116)
R2N (CO)5W NR2 (CO)5W
P
P
P
P
30%
P
NR2
But P
NR2
P
But
But
W(CO)5 (121) Scheme 33
Phosphaalkyne "005# reacts with phosphorus ð77AG"E#278Ł and arsenic ð77AG"E#698Ł heterocycles "011#[ In the former case a 1 ] 0 cycloaddition product is obtained whereas in the latter the reaction leads to a 2 ] 0 cycloaddition product minus the elements of benzonitrile "Scheme 23#[ But But
But
Ph
As P But P Ph
X = As P But
Ph
P
P X=P P But
N
P Ph
15%
70%
Ph
X
But P
Ph
Ph
(122)
N
Ph
Scheme 34
"iv# From phosphorus analo`ues of cyclopentadiene Di! and triphosphacyclopentadiene anions oligomerise under the in~uence of transition metals to give complex polycyclic products such as "012# "Equation "4## ð78CC0935\ 81JOM"322#C00\ 82CC200Ł[ But P
But
But
+
–
P Li+
P
–
But
P
P
FeCl3 or CoBr2
P P
24%
Li+
But But
P
But
But
P
P
But
(5)
But
(123)
5[94[0[1[2 Functions bearing heptavalent phosphorus The _rst report of this type of function utilised the reaction of triethyl phosphite with benzoyl peroxide in chloroform to form the tris"phosphonate# "013# ð52JCS0416Ł^ the same product was obtained from the benzoylphosphonate "014#[ The authors report that neither carbon tetrachloride
Three Group 04 Elements
044
nor diethyl ether were satisfactory solvents for this reaction[ Several patents claiming similar compounds as detergents appeared subsequent to this report ð58USP2360395\ 64USP2781565\ 66USP3919980\ 73USP3339535Ł[ More recently\ generation of the quinonoid "015# and subsequent reaction with diethyl phosphite in the presence of a base has been used to prepare the tris"phos! phonate# "016# in good yield "Scheme 24# ð89PS"36#6Ł[ Gross et al[ have developed this basic method further to produce compounds bearing di}erently substituted phosphorus functions\ e[g[\ "017# ð80PS"51#24Ł[ O
Ph P(OEt)3, CHCl3
(PhCO2)2, CHCl3, 48 h
P(OEt)3
PO(OEt) PO(OEt) (124)
(EtO)OP
40%
But
But PO(OEt)2
HO PO(OEt)2
PbO2
PO(OEt)2
O (125) But
HPO(OEt)2 NaOEt
O
PO(OEt)2 PO(OEt)2 PO(OEt)2
HO
80%
PO(OEt)2
But
P(OEt)2
Ph
32%
71%
But
But (126)
(127)
But POPh2 PO(OEt)2 PO(OEt)2
HO But (128)
Scheme 35
5[94[0[2 Functions Bearing Three Arsenic Atoms This author could locate only two reports referring to this functional group[ Tris"diphenyl! arsino#methane "029# was prepared by reaction of the lithium salt of bis"arsine# "018# with chloro! diphenylarsine ð71OM0003Ł[ The product was used in a study of its complexation properties[ In the second report ð82AG"E#092Ł tris"trimethylsilyl#phosphine was desilylated with butyllithium and the resulting lithium salt "020# treated with the arsaalkene "021# in the presence of cobalt"II# chloride to give tetraarsacubane "022# in moderate yield[ The reaction probably proceeds via an intermediate arsaalkyne "Scheme 25#[
Ph2As
AsPh2
i, BuLi, TMEDA ii, Ph2AsCl 60%
AsPh2 Ph2As
(129)
AsPh2 (130) But
O-TMS TMS-As But
(TMS)2PLi
But
As
CoCl2
As
35%
(131)
But
(132) Scheme 36
As As
(133)
As But But
At Least One Group 04 Element
045
5[94[0[3 Functions Bearing Three Antimony or Bismuth Atoms This author was unable to locate any references to the functional groups of either of these types in the literature[
5[94[0[4 Functions Bearing Nitrogen and Other Group 04 Elements 5[94[0[4[0 Functions bearing two nitrogen atoms and one phosphorus atom Gross and Costisella prepared compound "024# from the amidinium salt "023# by reaction with the sodium salt of diethyl phosphite ð58JPR814Ł^ Structure "024# was also made by treating uronium salts "025# with diethyl phosphite "Scheme 26# ð77ZOB1056Ł[ O Me2NH
+
+
Me2N OMe MeSO4–
O
Me2N
(EtO)2PNa
Me2N NMe2 MeSO4–
(EtO)2PH
+
Me2N
PO(OEt)2
OR Me2N
Me2N
(134)
X– (136) R = Me, X = MeSO4– R = Et, X = BF4–
(135)
Scheme 37
The iminium salt "027#\ which was prepared from phosphonate "026# ð60LA"649#33Ł\ reacted readily with a variety of amines to give the phosphonates "028# or with arylsulfonamides to give "039#[ Similarly\ ammonia was added across the imine bond of phosphonates "030# "Scheme 27# ð80PS"52#84Ł[ RO RO
O P
RO
OMe
SOCl2
RO
O Cl–
P +
NMe2 (137)
NMe2 (138)
R2NH 39–95%
EtO EtO
O P
NR2
NMe2 (139)
ArSO2NH2
EtO EtO
O P
NHSO2Ar NMe2 (140)
NCHO Cl3C PO(OR)2
NH4OH/CH2Cl2 R = Et, 85% R = Pri, 73%
Cl3C
NH2 NHCHO PO(OR)2
(141) Scheme 38
The cyclic orthoamide "031# was treated _rst with diethyl phosphite then with benzylamine to yield the bis"amino#methylphosphonate "032# ð89PS"36#150Ł[ The reaction of the tetraaminoalkene "033# with two equivalents of a dialkyl phosphite gave good yields of the imidazolidines "034# as illustrated in Scheme 28 ð67LA05Ł[ Heating a mixture of pyrazolone "035#\ diethanolamine and phosphite "036# gave the heterocycle "037# ð67MIP76757Ł[ Other cyclic examples "049# were prepared by the cycloaddition of an azide to aminophosphenes "038# but these derivatives were unstable above −59>C ð78NJC780Ł[ The reaction of N!phenylbenzohydrazonoyl chloride to 1\4!dimethyl!0\1\2!diazaphosphole "040# occurs by a multistage cycloaddition process involving two equivalents of the derived nitrile imine and the elimination of benzonitrile to give the bicyclic example "041#\ albeit in low yield "Scheme 39# ð72CB438Ł[
Three Group 04 Elements
046
O
O
i, (EtO)2PH, ∆
OEt
ii, Ph
NH
OH
NH2
H N
H N
32%
O
O (142)
Ph
PO(OEt)2 (143)
Ph Ph
Ph
O
N
N
(RO)2PH, ∆
N
N
N
R = Me, 92% R = Et, 93% R = Bun, 82%
N
Ph Ph
O P(OR)2
Ph
(144)
(145) Scheme 39
OH
OH
,∆
HN
O Me
N N
O
+
P
RO
OH
OR
Ph (146)
OH
N
PO(OR)2 Ph (148)
(147) R2
Ph
R2
< –60 °C
+ PhN3
PhP
N
N
Me
H R = CH2CH(Me)Cl
N
N(Me)R1 (149)
N(Me)R1
P
N Ph N (150) Ph
Ph
N
+
MeN P
NNHPh Cl
base
NNHPh
N MeN P
N MeN
Cl
NHPh
P Et3N 21%
(151)
Ph
NHPh N N
Ph
(152) Scheme 40
5[94[0[4[1 Functions bearing two phosphorus atoms and one nitrogen atom "i# Introduction This type of functional group has been most widely prepared in the pharmaceutical industry\ where such compounds are patented as agents for treating abnormal calcium and phosphate metabolism such as the bone disorder Paget|s disease\ "e[g[\ ð78EUP187442Ł#[
"ii# Synthesis from ortho!esters and similar derivatives Gross et al[ have published details of the preparation of aminobis"phosphonato#methanes "042# and the corresponding bis"phosphine# oxides "043# by a method which involves heating ortho!amides either with dialkyl phosphites or with phosphine oxides "Scheme 30# ð57AG"E#280\ 57AG"E#352\ 58JPR466Ł[ Thus\ the cyclic ortho!amide "031# was treated _rst with diethyl phosphite and then diethyl trimethylsilylphosphite to give bis"phosphonato#methane "044# in moderate yield ð89PS"36#150Ł[ The aminopyridine derivative "046# was prepared by the reaction of triethyl ortho! formate with 2!methyl!1!aminopyridine and two equivalents of phosphinite "045# ð70PS"00#200Ł[
At Least One Group 04 Element
047
Similar chemistry using a mixture of phosphorus species resulted in the analogues "047# ð89PS"40:41#12Ł\ which were also made from the diethoxyphosphinyl acetal "048#[ O
O
PO(OR)2
OMe
(RO)2P H, ∆
Me2N
Me2N
60–69%
PO(OR)2
POR2
R2P H, ∆
Me2N
55–70%
OMe
POR2 R = Bun, Ph (154)
R = Me, Et (153) Scheme 41
O
OEt
O
HPO(OEt)2
NH
PO(OEt)2 NH
58%
O
OH
TMS-PO(OEt)2
H N
48%
O
O
(142)
PO(OEt)2
(6)
PO(OEt)2 (155)
O P
150 °C
+ HC(OEt)3 + 2 MeP(OH)OEt N
68%
(156)
NH2
N
N H (157)
O P N
N H
Me OEt
(7)
P Me OEt O
OH R
(EtO)2PCH(OEt)2
P(OEt)2 O (159)
(158)
"iii# Synthesis from amides Amides have been treated with hydrochloric and phosphorous acids to give variable yields of aminobis"phosphonates# "059# ð61ZAAC"278#008Ł^ the reaction of formamides with phosphorus trichloride or tribromide followed by acid hydrolysis resulted in similar compounds ð64BCJ0929Ł[ Using a similar procedure\ chloroacetamide "050# was transformed into the corresponding derivative "051# by a mixture of phosphorus trichloride and phosphorous acid ð68ZAAC"346#103Ł and the same method was used to prepare "052# ð74LA444Ł[ The unusual phosphorous oxide "P3O5# has also been applied to the synthesis of these functions "Scheme 31# ð89PS"40:41#042Ł[ Wet DMF when treated with two equivalents of phosphorus trichloride and then more water\ gave the dimethylamino derivative "053# in good yield\ as shown in Equation "7# ð80PS"45#006Ł[ R1CONR2R3•HCl
H3PO3
R2R3N
21–77%
NH2
Cl O (161)
i, PCl3/H3PO3, dioxan ii, H2O, ∆
PO(OH)2 PO(OH)2 R1 (160) PO(OH)2
Cl
PO(OH)2
42%
2 RCONH2 + P4O6 + 4 H2O
NH2 (162)
70–98%
Scheme 42
R
NH2 PO(OH)2 PO(OH)2
Three Group 04 Elements
048
PO(OH)2 H2N PO(OH)2 (163)
Me2NCHO
i, PCl3 ii, H2O
PO(OH)2 Me2N
70%
(8) PO(OH)2 (164)
"iv# Synthesis from nitriles The earliest report of the preparation of this type of functional group utilised the reaction of nitriles with phosphorus trihalides and water ð46GEP091244Ł[ This method was subsequently used by Worms and Blum to prepare aryl derivatives "054# ð68ZAAC"346#198Ł[ In addition\ these workers used the reaction of cyanocyclohexane with phosphorous acid to obtain the cyclohexyl analogue "055#[ This transformation can be carried out in the presence of a ketone] Blum and Hemman reported that ketone "057# was made from the nitrile "056# and a mixture of phosphorus tribromide and phosphoric acid "Scheme 32# ð77GEP2500411\ 77ZN"B#64Ł[ PO(OH)2 PO(OH)2 NH2
PBr3, H2O
ArCN
Ar Ar = Ph 60%
(165) CN
PO(OH)2 PO(OH)2
H3PO3
NH2
74%
(166) O CN
R
O
H3PO4, PBr3, dioxan R = t-alkyl 38–66%
PO(OH)2 PO(OH)2
R
NH2 (168)
(167) Scheme 43
"v# Synthesis from imidoyl compounds The reaction of imidate "058# with sodium diethyl phosphite in benzene gave tetraethyl bis"phos! phonato#benzylamine "069# ð48LA"512#092Ł[ In a similar way\ diethyl phosphite was added to imidoyl! phosphonate "060# to give aminobis"phosphonato#methane "061# "Scheme 33# ð60LA"649#33Ł[ The treatment of imidoyl halides with phosphorous acid gave rise to the parent acids "062# ð61ZAAC"278#008Ł and similar functions "063# and "064# were obtained using triethyl phosphite ð70PS"00#200\ 71SC304Ł and diethyl phosphinite ð70PS"00#200Ł\ respectively[
"vi# Synthesis from other bisphosphorus species In attempts to prepare aminotris"phosphonato#methanes "066# by addition of diethylphosphite to the imine bond in "065# Gross and Costisella actually obtained the product of reduction "067# via an unexpected carbon to nitrogen phosphorus migration "Scheme 34# ð61JPR858Ł[ This method has since been used to prepare similar derivatives "068# ð63PS"3#130\ 65JPR161Ł[
At Least One Group 04 Element
059
O
NH
(EtO)2P
Ph
H , Na, benzene 63%
OEt
PO(OEt)2 PO(OEt)2 NH2
Ph
(170)
(169) O
O
(EtO)2P
+
NMe2 Cl–
(EtO)2P
PO(OEt)2
H
H2N
39%
PO(OEt)2
(171)
(172)
+
H3PO3
NR2R3 Cl–
R1
PO(OH)2 PO(OH)2 NR2R3
R1
15–78%
Cl
(173) Scheme 44
O PO(OEt)2
P
R2N
Me2N PO(OEt)2
Me OEt Me
P OEt O (175)
(174)
O
PO(OEt)2
(EtO)2P
R 1N PO(OEt)2
H
R1 = Ar, 23–71%
(176)
PO(OEt)2 R1HN PO(OEt)2 (178)
PO(OEt)2 PO(OEt)2 PO(OEt)2
R1HN
(177) Scheme 45
POPh2 R1HN POPh2 (179)
"vii# Miscellaneous syntheses The reaction of aryl isocyanides "079# with dialkyl phosphites and base is reported to give the anilines "070# ð64ZOB0349Ł[ Ferric chloride catalysed displacement of chloride from isocyanate "071# by ~uorophosphite yields the unusual isocyanate "072# ð66ZOB210Ł[ Dehydration of the aminoalcohol "073# by heating with hexamethyldisilazane gave rise to a mixture of bis"phosphonato#pyrrolidine "074# and the product of further loss of phosphite "Scheme 35# ð89PS"43#086Ł[ Diphosphacyclobutanes "076# have been obtained by dimerisation of the phosphorous analogues "075# of amidines ð79ZAAC"351#029\ 71ZAAC"374#12\ 72PS"07#16\ 80PS"50#250Ł[
Three Group 04 Elements
050 R2OP
O R 2P
R1
NC
POR2
H , alkoxide
R1
58–75%
N H
R = alkoxy, alkyl
(180)
(181) O
Cl
+
OCN
P
FeCl3
2 (EtO)2PF
OCN
30%
Cl
P O (183)
(182) PO(OH)2 OH NH2
(TMS)2NH
PO(OH)2
PO(O-TMS)2 N H
(184)
+
N
PO(O-TMS)2
OEt F OEt F
PO(O-TMS)2
(185) NMe2 RP
RP NMe2
PR Me2N
(186)
(187) Scheme 46
5[94[0[4[2 Functions bearing nitrogen and other group 04 elements Kellner et al[ described the reaction of diphenylarsane with tetramethylamidinium chloride in acetonitrile to give bis"dimethylamino#methyldiphenylarsane "077# ð67JOM"038#056Ł[ This reaction proceeds in poorer yield when the sodium salt of the arsane is used in THF[ Imidoyl chloride "089# forms the cyclic derivative "080# by reaction with aminoarsane "078# "Scheme 36# ð67ZC341Ł[ Treatment of arsenadiazole "081# with diphenylnitrile imine gives the bicyclic analogue "082# ð75TL1846Ł[ AsPh2
HAsPh2, MeCN
+
Me2N
Cl–
NMe2
NMe2 Me2N (188)
78%
Et
Et AsH
But
NPh
BuLi, Et2O
+ Cl
NH
Et But
As NH
NH
As
But
N
NHPh
Et
Et
Et (189)
(190)
(191) Ph
MeOC Ph
N MeOC
N
As
NNHPh
N
20 °C
+
N 70%
Cl
N As
N Ph
(192)
(193) Scheme 47
The bis"nitro#methylstibane "083# is formed when the silver salt of 0\0!dinitroethane is treated with diphenylstibyl chloride\ as shown in Equation "8# ð74IZV328Ł[
At Least One Group 04 Element
051
CH2Cl2, <10 °C
MeC(NO2)2Ag + Ph2SbCl
NO2 NO2
Ph2Sb
(9)
90%
(194)
5[94[1 FUNCTIONS CONTAINING GROUP 04 ELEMENTS WITH METALLOIDS 5[94[1[0 Functions Bearing Group 04 Elements and Silicon 5[94[1[0[0 Functions bearing nitrogen and silicon "i# From silyl halides This general method involves deprotonation of the carbon atom attached to a nitrogen function followed by silylation[ Thus\ methyl isocyanide has been successively deprotonated and silylated to a}ord bis"trimethylsilyl#methyl isocyanide "084# ð69JOM"14#274Ł\ the second silylation going in much poorer yield than the _rst[ The product "084# was converted to the corresponding isothiocyanate using sulfur ð71BCJ0052Ł[ Katritzky et al[ prepared bis"trimethylsilyl#methylbenzotriazole "085# by the same method and studied its further alkylation "Scheme 37# ð77RTC530Ł[ More recently\ Snieckus and co!workers showed ð78TL4730Ł that whereas N\N!dimethylbenzamide could be readily silylated using lithium tetramethylpiperidide to yield "086#\ the corresponding diethylamide or piperidide gave O!silyl products[
MeNC
i, BuLi, –78 °C ii, TMS-Cl 80%
i, BuLi ii, TMS-Cl
TMS
i, LDA/THF –78 °C ii, TMS-Cl
N N
90%
N
NC
TMS
40%
N N N
TMS
TMS NC (195) i, BuLi ii, RX
N
R = Me, 90% R = PhCH2, 95%
N
N
TMS
TMS
TMS LDA = lithium diisopropylamide
TMS R
(196) O
O NMe2
i, LiTMP, THF ii, TMS-Cl
TMS N Me
TMS
(197) Scheme 48
"ii# By reductive silylation Amides have been treated with silyl halides in the presence of metals to give bis"tri! methylsilyl#aminomethanes[ Thus\ N\N!dimethylbenzamide\ when added to TMS!Cl and mag! nesium in hexamethylphosphoramide "HMPA#\ gave "087# in modest yield ð60JOM"21#68Ł[ The authors report that the reaction fails using N!methylbenzamide[ Ekouya et al[ studied the same reaction using formamides and lithium metal in THF and found the addition of triethylamine to be advantageous ð68JOM"066#026Ł[ In this case\ the product "088# was formed in only trace amounts in the absence of base "Scheme 38#[ Picard et al[ made bis"trimethylsilyl#aminomethane "199# in good yield by treatment of TMS!CN with TMS!Cl and lithium in HMPA ð80JOM"308#C0Ł[
Group 04 with Metalloid"s#
052
TMS-Cl, Mg, HMPA
Ph
PhCONMe2 32%
TMS
TMS-Cl, Li, THF, Et3N
HCONH2
NMe2 TMS TMS (198)
TMS N
30%
TMS
TMS (199)
i, TMS-Cl, Li, HMPA ii, MeOH
TMS H2N
TMS-CN 65%
TMS (200)
Scheme 49
"iii# Miscellaneous methods Bis"trimethylsilyl#chloromethane has been reported to react with sodium azide in HMPA^ sub! sequent reduction using LAH leads to the amine "199# "Equation "09## "ð80JOM"308#C0\ 81TL2892Ł#[ TMS
TMS
NaN3, HMPA
Cl
(10)
H2N
76%
TMS
TMS
TMS
LAH, Et2O
N3
TMS (200)
Silaneimine "190#\ when treated with dimethylethylamine at elevated temperatures\ inserts into two of the C0H bonds of a methyl group of the amine resulting in the formation of the silaneamine "191# "Scheme 49# ð76CB0246Ł[ +
Me2Si
EtNMe2
NSiBut
3
NMe2Et –
SiMe2NHSiBut3
135°C
Me2Si
67%
MeEtN NSiBut3
39%
SiMe2NHSiBut3 (202)
(201)
TMS
NC
Me2 Si
TMS
TMS
TMS
Me2 Si
TMS
Me2Si TMS Pd(OAc)2
N
LAH, Et2O
56%
(203)
NH HN
N 85%
(204)
(205)
Scheme 50
The aryl isocyanide "192# reacts with octamethyltrisilane in the presence of a palladium catalyst to give the bis"silylimine# "193# which when reduced with LAH results in the formation of the corresponding amine "194# in good yield ð77JA2581Ł[
5[94[1[0[1 Functions bearing phosphorus and silicon "i# From silyl halides In a manner exactly analogous to the nitrogen series\ the quenching of a phosphorus stabilised carbanion by a silylating agent has been widely used to prepare this functional group[ Phosphine
At Least One Group 04 Element
053
sul_de "196# was prepared by reaction of the lithium salt "195# with excess TMS!Cl ð63ZAAC"393#193Ł[ Phosphines "197# have been further silylated in good yields ð70ZAAC"364#07\ 73CB1952Ł and phos! phonates "198# have been similarly treated "Scheme 40# ð76JOM"212#024Ł[ Trimethylphosphine has been doubly deprotonated using t!butyllithium and successively silylated to give "109# ð77ZN"B#0305Ł[ S Li
P
Ph
TMS-Cl
Ph
65%
S TMS
i, BuLi, TMEDA ii, TMS-Cl
R P
Me
P
OR OR
Ph
TMS
P
R = alkyl, Ph, 41–65%
Ph
TMS O
i, LDA, THF ii, TMS-Cl
TMS
R = alkyl, 25–85%
(209)
PMe3
Ph
R
(208) O
Ph
TMS (207)
(206)
TMS
P
P
O
i, LDA ii, MeI
OR OR
TMS
P
91–92%
OR OR
TMS
TMS LDA = lithium diisopropylamide
i, ButLi ii, TMS-Cl
TMS
P
Me
i, ButLi ii, TMS-Cl
Me
TMS
Me
P
Me
TMS (210)
Scheme 51
Bis"phosphino#methanes "100# have been silylated using butyllithium as a base to a}ord bis"phos! phino#trimethylsilylmethanes "101# "Equation "00## ð68CB537\ 77ZN"B#0305Ł[ TMS
i, ButLi ii, TMS-Cl
PR2
R2P (211)
(11)
PR2
R2P (212)
R = Ph, Me
Phosphorus double bonded systems such as "102# and "103# react with nucleophiles at phosphorus "Scheme 41# ð72PS"07#32Ł[ Subsequent silylation in the case of "102# gave "104# whereas protonation at carbon in the case of "103# yielded "105#[ TMS R2NP
i, ButLi ii, TMS-Cl
TMS But2P
TMS
TMS
(213)
(215) i, MeLi ii, MeOH
P
Me P
TMS
TMS
TMS
TMS
(214)
(216) Scheme 52
"ii# From phosphorus halides Sequential replacement of halogens in phosphorus halides using silyl stabilised carbanions is another common method for the synthesis of this group[ Phosphorus trichloride when treated with
Group 04 with Metalloid"s#
054
the lithium salt of bis"trimethylsilyl#methane was converted to either the dichloro compound "106# or its analogous monochloride "107#\ depending on the proportions of the reagents ð79JCS"D#1317Ł[ Dialkyl! ð80AG"E#698Ł and diarylchlorophosphines ð72JCS"D#894Ł produce similar products and Grig! nard reagents have also been used with phosphorus trichloride ð89TL2748Ł and aryldichloro! phosphine "108# ð74OM228Ł "Scheme 42#[ Phosphinylidene chloride "119# was converted to the unsaturated derivative "110# in high yield ð71OM0619Ł[ Cl Li
Et2O, 25 °C
+ 1 PCl3
1
P
73%
TMS
TMS
TMS
Cl
TMS (217) Cl Et2O, ∆
Li
+ 1 PCl3
2
P
TMS
60%
TMS
TMS
TMS
TMS TMS (218) PCl2 Cl
MgCl
THF
+
P
TMS
TMS
TMS TMS (219) Li
TMS
Cl
TMS
P
TMS TMS
TMS
TMS P
79%
TMS
TMS (221)
(220) Scheme 53
The reaction of tris"trimethylsilyl#methyllithium with phosphorus trichloride produced the dichloride "111# ð78JOM"255#28Ł\ which\ after replacement of the halides using sodium methoxide\ gave dimethoxyphosphine "112# which readily desilylated in methanol to give bis"trimethylsilyl#! methane "113#[ This desilylation was previously noted in diphenylphosphine "114#\ which although stable under basic conditions was much less so at lower pH "Scheme 43# ð72JCS"D#894Ł[ TMS TMS TMS
Li
PCl3, Et2O-THF 65%
TMS TMS TMS
Cl
NaOMe
P Cl
95%
(222) TMS TMS TMS
TMS TMS TMS
OMe
TMS
72%
TMS
TMS
OMe P
OMe
(223)
MeOH, RT
MeOH
P 97%
TMS
OMe
(224)
PPh2
PPh2
(225) Scheme 54
"iii# Miscellaneous methods Phosphinylidene derivatives have been reduced under a variety of conditions[ For example\ the phosphine "115# was produced e}ectively by the transfer of hydride from a phosphinyl methyl group ð73ZAAC"400#097Ł[ In another case\ phenylphosphinylidene disilane "116#\ when treated with an equimolar mixture of phenylphosphine and its sodium salt ð76CB0696Ł\ gave the product "117# in
At Least One Group 04 Element
055
high yield and the chloro analogue "118# has been reduced with concomitant disproportionation using LAH "Scheme 44# ð76CC0981Ł[ TMS
TMS
Cl
+ TMS
Me2 P PMe2
TMS-PMe2
Cl
TMS TMS
TMS PHPh TMS (228)
82%
TMS (227)
PMe2 TMS (226)
60%
PhPH2, PhPHNa
PPh
TMS
toluene, 100 °C
H
TMS
LAH
PCl
TMS
TMS (229)
TMS
P
TMS
TMS Scheme 55
The displacement of chloride ion from phosphinylidene chloride "129# with acetylide anions gives rise to the diphosphacyclobutane "120# after dimerisation as a mixture of stereoisomers ð73CB1582Ł[ Interestingly\ the aminophosphinylidene compound "121# dimerises with rearrangement to the unusual small ring compound "122# "Scheme 45# ð89CB0134Ł[ Phosphinylidene compounds also undergo cycloadditions[ For example\ 1\2!dimethylbutadiene gave the phosphorus heterocycle "123# ð74CB703Ł and diphenyldiazomethane the three!membered epiphosphine "124# ð75CB0866Ł[ Ph
TMS TMS
M
+
ClP
TMS
TMS
P
Ph
Ph
(230)
P
TMS
TMS (231)
TMS TMS TMS-NHP TMS
∆
TMS
P
65%
N TMS
P
(TMS)2N
TMS
(233)
(232)
TMS ClP TMS
, C6H6, RT 89%
P Cl
TMS ButP TMS
TMS TMS (234)
But Ph2CN2
P Ph
77%
TMS Ph TMS (235)
Scheme 56
Pentamethylcyclopentadiene groups in the diphosphene "125# have been displaced by the lithium salt of bis"trimethylsilyl#methane to form the new diphosphene "126# as shown in Equation "01# ð75AG"E#808Ł[ TMS Li
P
P
TMS
TMS
TMS P
TMS
TMS (236)
(12)
P
(237)
Group 04 with Metalloid"s#
056
"iv# Modi_cation at phosphorus There have been a number of reports in which previously formed functions have been modi_ed at phosphorus[ Chlorophosphines such as "127# have been reduced using\ for example\ sodium metal or LAH ð71OM0619\ 74OM228Ł[ Alternatively\ the halogen was replaced by a methyl group "Scheme 46# ð73CC0558Ł[ The phosphine oxide "139# has been produced from its parent compound "128# by a mild oxidation which avoids decomposition ð73JOC4976Ł\ and the reaction of bis"phos! phino#methane "130# with sulfur gives the analogous thio compound "131# ð81CB0222Ł[ Cl
H TMS
TMS
P
82%
TMS
TMS
TMS
LAH
Me TMS
P
TMS
Li, MeCl
TMS
TMS
P
TMS TMS
TMS
(238) O
Ph H2O2, acetone, 4 °C
P
TMS
Ph
Me
Ph
89%
TMS (239) Me
Ph
P
TMS
TMS (240) Me P
P
Me
S8, toluene, 50 °C
Me
95%
Me
S
S
P
P
TMS (241)
Me Me
TMS (242) Scheme 57
The bis"trimethylsilyl#methyl group has\ by virtue of its steric bulk\ been used as a stabilising group in the preparation of bisphosphenes "for a review see ð73POL278Ł# e[g[\ the reaction of dichloride "106# with hindered phosphine "132# in the presence of 0\4!diazabicyclo ð4[3[9Ł undec!4! ene "dbu# gives bisphosphene "133# ð72CC417Ł[ The analogue "126#\ prepared by treating di~uoride "134# with lithiophosphine "135#\ had a half!life of one week at 19>C ð76PS"20#70Ł[ The same stabilising e}ect has been utilised in producing phosphinyl radicals "136# ð79JCS"D#1317Ł which were subsequently shown to add to 1\2!dimethylbutadiene to give the corresponding bis"phosphines# "137# "Scheme 47# ð73TL2408Ł[
PH2 Cl
TMS
But
But
But
TMS
THF, dbu
P
P 78%
Cl
TMS
TMS But
But (243)
(217) TMS
(244)
TMS PF2
+
TMS
PHLi TMS
(245)
i, Et2O, pentane ii, dbu
TMS
85%
TMS
P TMS
TMS (237) TMS
TMS
TMS P
(246) • P
But
P
TMS TMS
TMS TMS TMS
P
P
TMS
TMS TMS (248)
(247) Scheme 58
TMS
At Least One Group 04 Element
057
5[94[1[0[2 Functions bearing nitrogen\ phosphorus and silicon The cycloadditions of t!butyl! ð70AG"E#020Ł and trimethylsilyldiazomethane ð72CC0060Ł with phosphinylidenemethylsilane "138# gave the corresponding heterocyclic examples "149# shown in Equation "02#[ TMS TMS
RCHN2, THF
N P TMS
R = But, TMS
TMS
TMS
N
N P
N
TMS
(13)
R (250)
(249)
5[94[1[0[3 Functions bearing arsenic\ antimony or bismuth "i# From trihalides The displacement of one or more halides from the appropriate trihalides has proved the method of choice for the preparation of these functions[ Gynane et al[ ð79JCS"D#1317Ł produced arsenic and antimony derivatives with either one "140# or two bis"trimethylsilyl#methyl groups "141# by the reaction of appropriate trichlorides with the correct proportions of bis"trimethylsilyl#methyllithium[ Bismuth derivatives with three such substituents "142# were similarly prepared ð72IC2310Ł and Grignard reagents have also been used for the synthesis of stibanes "143# ð72POL180\ 73IC1471Ł[ More recently\ the pyridyl derivatives "144# were produced in a similar way ð80CC0459Ł "Scheme 48#[ TMS MCl3 +
Et2O
Li M = As, 70% Sb, 60%
TMS
TMS MCl3 +
2
Et2O
TMS MCl2 TMS (251) TMS MCl
Li M = As, 61% Sb, 65%
TMS
TMS
2
(252) TMS BiCl3 +
Et2O, 0 °C
TMS Bi
Li
3
90%
TMS
TMS
3
(253) TMS SbCl3 +
Et2O, –40 °C
MgCl 74%
TMS
TMS
N Li
TMS SbCl2 TMS (254)
MCl3, Et2O, –80 °C
TMS
M = As, 55% Sb, 70% Bi, 44%
N
TMS TMS MCl2 (255)
Scheme 59
"ii# By modi_cation of the `roup 04 element As in the case of the diphosphenes\ bis"trimethylsilyl#methyl groups have been used to stabilise heteroatomic double bonds[ Diarsenes "147# were prepared ð72JA4495Ł by reaction of aryl arsane
Group 04 with Metalloid"s#
058
"145# with dichloroarsane "146# "Equation "03##\ whereas mixed functions "148# were made by reacting the corresponding phosphine with arsenic and antimony dichlorides ð72CC770Ł[ AsH2 TMS
But But
But
+
AsCl2
THF, dbu
TMS
72%
TMS
As
TMS
But
(14)
But
But (257)
(256)
As
(258)
But TMS But
P
M TMS
But (259) M = As, Sb
The chloroarsane "159# was metallated on treatment with lithium[ Subsequent protonation or methylation produced the arsanes "150# whereas reaction with stannous chloride gave diarsane "151# ð76JOM"219#C16Ł[ Treatment of dichlorostibane "143# with magnesium in THF resulted in the formation of the unusual cyclotetrastibane "152# "Scheme 59# ð81OM034Ł[ TMS As TMS
i, Li ii, SnCl2, Et2O
TMS As TMS
2
TMS AsCl
70%
TMS
2
2
i, Li ii, electrophile
TMS
E = H ex HCl, 90% E = Me ex MeCl, 73%
TMS
(260)
(262)
AsE 2
(261) TMS TMS
TMS
TMS
Mg, THF
Sb
Sb
Sb
Sb
TMS
SbCl2 TMS
TMS
TMS
TMS TMS (263)
(254) Scheme 60
5[94[1[1 Functions Bearing Group 04 Elements and Boron A search of the literature revealed many references to carborane chemistry and readers are referred to specialist texts for further information on this complex subject ðB!69MI 594!90\ 71COMC! I300\ 71COMCI!I432\ 81CRV198Ł[ In the sole report of a simple example uncovered by this author\ Io}e et al[\ disclosed the synthesis of "153# by treatment of dinitromethane salts with chlorodiethylborane "Equation "04## ð63MI 594! 90Ł[ Et2BCl + (NO2)2CH2
base
Et2BCH(NO2)2 (264)
(15)
5[94[1[2 Functions Bearing Group 04 Elements and Germanium Karsch et al[ ð75JOM"201#C0Ł made germanium compounds "154# and analogous lead derivatives by the reaction of the lithium salt of bis"diphenylphosphinyl#methane with germanium"II# chloride "Equation "05##[ GeCl2, –40 °C
(Ph2P)2CHLi 93%
Ge[CH(PPh2)2]2 (265)
(16)
At Least One Group 04 Element
069
5[94[2 FUNCTIONS CONTAINING GROUP 04 AND METAL ELEMENTS\ AND POSSIBLY A METALLOID Many such compounds have been prepared without isolation or characterisation as precursors to the functional groups mentioned earlier in this chapter and hence relevant references can be found above[ The subsequent discussion will refer only to those areas previously uncovered or where the chemistry is signi_cant enough to be considered separately[ Work has been done in the area of organometallic cluster compounds but this falls outside the scope of this chapter[ Many alkali metal salts of dinitromethane derivatives have been made ð46JA3697\ 50JOC3623Ł[ It has been shown by x!ray di}raction that the rubidium salt of cyanodinitromethane exists in a form in which the metal atom is closely associated with one of the oxygens ð61ACS0763Ł[ It seems highly likely that alkali metal salts of other systems\ where delocalisation is possible\ will behave similarly[ The reaction of dinitromethane with triethylthallium gave a compound of Structure "155# in which the metal is reported to coordinate to both carbon and oxygen atoms "Equation "06## ð60IZV0494Ł[ CH2(NO2)2 + TlEt3
Et2O
Et2TlCH(NO2)2 (266)
95%
(17)
The deprotonation of bispyrrole "156# has been achieved using methyllithium and although formal resonance structures are di.cult to write for the lithium salt\ NMR studies indicate extensive delocalisation of charge ð79HCA0089Ł[ Katritzky et al[ have studied the use of benzotriazole as a stabilising group for anionic centres^ among recent publications is one concerning the generation and use of organolithium species "157# ð80JOC1032Ł[ N N N N Li N
N
(267)
(268)
Kau}mann and his group have studied the chemistry of the deprotonation of carbon atoms attached to heavy metals and metalloids\ and a review has appeared ð71AG"E#309Ł[ In some cases the loss of one of the metal substituents is observed[ The preparation of lithium salts of bis"di! phenylstibanyl#methane and bis"diphenylarsanyl#methane and the subsequent deuteration of the products "158# has also been described "Equation "07## ð68TL490Ł[ (Ph2M)2CH2
c-Hex2NLi, HMPA
(269)
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
(Ph2M)2CHLi
D2O M = Sb, 68% M = As, 63%
(Ph2M)CHD
(18)
Comprehensive Organic Functional Group Transformations
6.06 Functions Containing at Least One Metalloid (Si, Ge, or B) and No Halogen, Chalcogen or Group 15 Element; Also Functions Containing Three Metals VADIM D. ROMANENKO Institute of Organic Chemistry, Kiev, Ukraine MICHEL SANCHEZ Universite´ Paul Sabatier, Toulouse, France and JEAN-MARC SOTIROPOULOS Universite´ de Pau et Pays de l’Adour, Pau, France 5[95[0 INTRODUCTION
061
5[95[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION "AND NO HALOGEN\ CHALCOGEN\ OR GROUP 04 ELEMENT# 5[95[1[0 Functions Containin` Three Metalloids 5[95[1[0[0 Functions bearin` three silicons 5[95[1[0[1 Functions bearin` three borons 5[95[1[0[2 Functions bearin` three `ermaniums 5[95[1[0[3 Functions bearin` mixed metalloids 5[95[1[1 Functions Containin` Metalloids and Metals 5[95[1[1[0 Functions bearin` silicon"s# and metals"s# 5[95[1[1[1 Functions bearin` boron"s# and metal"s# 5[95[1[1[2 Functions bearin` `ermanium"s# and metal"s# 5[95[1[1[3 Functions with mixed metalloid"s# and metal"s# 5[95[2 FUNCTIONS CONTAINING THREE METALS
061 061 061 079 074 075 078 078 087 191 192 193 193 193
5[95[2[0 Three Similar Metals 5[95[2[0[0 Lithium derivatives\ RCLi2
060
061
At Least One Metalloid or Metal
5[95[2[0[1 Mercury derivatives\ RC"H`X#2 5[95[2[0[2 Aluminum derivatives\ RC"AlX1#2 5[95[2[0[3 Tin and lead derivatives\ RC"MX2#2 "M Sn or Pb# 5[95[2[1 Three Dissimilar Metals
195 197 197 198
5[95[0 INTRODUCTION This chapter deals with compounds of the general formula RC"EXm#n"MLk#2−n "E Si\ Ge\ or B^ M metal^ R H or organyl^ X any substituent^ n 9Ð2# having three heteroatoms "E\ M# bonded to the same carbon[ Most of the organoelement species of this type contain classical two! center\ two!electron {{single|| bonds and formally arise through the replacement of hydrogen atoms with the heteroatoms mentioned[ It is the purpose of this chapter to discuss the preparation and some of the chemical transformations of these compounds[ A discussion of carboranes\ metal clusters\ and other electron!de_cient molecules which cannot be portrayed in the same manner and exhibit quite di}erent reactivities\ is not included[ For the same reason\ p!metal complexes containing a C"EXm#n"MLk#2−n fragment are also ignored[ However\ the organometallic compounds of the type RC"EXm#nM2−n "M alkali metal#\ often better described as heteroatom!stabilized carbanions\ are considered[ As will become evident\ the methods of preparation of the above functions are wide and varied[ Some of these methods are discussed in monographs by Colvin ðB!70MI 595!90Ł\ Weber ðB!72MI 595! 90Ł\ Pereyre et al[ ðB!76MI 595!90Ł\ and Negishi ðB!79MI 595!90Ł[ The latter also contains a detailed discussion of standard methods of carbonÐmetalloid and carbonÐmetal bond formation[ Houben! Weyl|s Methoden der Or`anischen Chemie ð63HOU"02:1b#0\ 64HOU"02:6#0\ 67HOU"02:5#070\ 79HOU"02:4#16\ 71HOU"02:2a#0Ł and the appropriate reviews in Comprehensive Or`anometallic Chemistry ð71COMC! I"1#0\ 71COMC!I"6#154\ 71COMC!I"6#404Ł etc[ and Comprehensive Or`anic Chemistry ð68COC"2#576Ł cover parts of the literature up to 0871[ The preparation and properties of some polyborylated compounds are also discussed in a monograph by Pelter et al[ ðB!77MI 595!90Ł and in a book by Pelter ðB!76MI 595!91Ł[ The chemistry of polylithiated aliphatic hydrocarbons has been reviewed by Maercker and Theis ð76TCC"027#0Ł[ Discussion of certain aspects of the topic can also be found in Comprehensive Or`anic Synthesis ð80COS"0#0\ 80COS"0#376Ł and in a number of other references[ ð53AOC"1#146\ B!56MI 595!90\ B!74MI 595!90\ B!74MI 595!91\ 75MI 595!90\ 78MI 595!90\ B!78MI 595!91\ B!81MI 595!90Ł[
5[95[1 FUNCTIONS CONTAINING AT LEAST ONE METALLOID FUNCTION "AND NO HALOGEN\ CHALCOGEN\ OR GROUP 04 ELEMENT# 5[95[1[0 Functions Containing Three Metalloids 5[95[1[0[0 Functions bearing three silicons Trisilylmethyl groups\ especially tris"trimethylsilyl#methyl\ "TMS#2C\ have been widely recognized as versatile building blocks in organic synthesis which have proven their synthetic utility in hundreds of reactions ð71JOM"128#82\ B!74MI 595!90\ 80MI 595!90\ 80MI 595!91Ł[ These burgeoning applications arise from the unique properties of trisilylmethyl derivatives[ Trialkylsilyl groups "R2Si# can be considered {{bulky protons|| and have been widely used for the synthesis of sterically protected molecules[ Due to the acidity of the Si2C0H hydrogen "and hence the availability of the corresponding metal derivatives#\ trisilylmethyl groups can be easily attached to a range of metals and metalloids[ Many of the resulting compounds show enhanced stability compared to the corresponding unsubstituted methyl derivatives and thus are easily handled and studied[ Lastly\ due to the steric as well as to the electronic e}ects trisilylmethyl groups can stabilize an adjacent carbanionic center or an adjacent carbonÐheteroatom double or triple bond[ The main synthetic pathways to 0\0\0!trisilylalkanes are] "a# {{direct synthesis|| in the gas phase involving insertion of silicon into a carbonÐhalogen bond^ "b# reductive silylation of trihalomethanes^ "c# reactions of organometallic carbon nucleophiles with chlorosilanes^
062
At Least One Metalloid
"d# derivatization and rearrangements of the compounds already containing polysilylated C0 units[ A number of other reactions in which an Si2C function is created are known\ but they are more of academic interest[
"i# Trisilylmethanes and their linear C!or`anyl derivatives\ RC"SiX2#2 Compounds of this type are known with R H\ alkyl\ aryl\ hetaryl\ acyl\ and with a variety of substituents on silicon[ The parent tris"silyl#methane "0# is formed in very low yield via LAH reduction of the corresponding chloro derivative "1# ð53CB0888\ 75ZN"B#0416Ł[ This precursor is available\ along with other trisilylated methanes such as structures "2#Ð"5#\ in the {{direct synthesis|| using a copper catalyzed reaction of elemental silicon with chloroform ð47CB11Ł or other halo! hydrocarbons ð74ZC298\ 82ZAAC"508#0383Ł[ SiH3
SiCl3
SiH3
H3Si
SiCl3
Cl3Si
(1)
TMS TMS
TMS
(2)
(3)
HC(SiHCl2)n(SiCl3)3–n (4)-(6); n = 1–3
Attempts were made to obtain tris"silyl#methane by the reaction of silylpotassium\ KSiH2\ with halomethanes ð50JA791\ 56IC0640\ 64JOM"81#052Ł and the pyrolysis of methylchlorosilanes ð56AG"E#566Ł\ but the yields were again in the lower region[ More recently\ tris"silyl#methane was obtained in high yield by a three!step synthesis presented in Scheme 0 ð78CB1004Ł[ An in situ Grignard reaction of easily accessible chlorophenylsilane with bromoform and magnesium gave tris"phenylsilyl#methane "6# in ca[ 49) yield[ The _nal conversion of bromo derivative "7# into tris"silyl#methane "0# has been accomplished through reduction with LAH in a two!phase system employing a phase transfer catalyst[ A similar route is suitable for the preparation of the homologous bis"silyl#methane ð89CB1976Ł and tetrakis"silyl#methane ð89AG"E#190Ł[ Br Br
SiH2Ph
PhSiH2Cl/Mg
Br
THF, reflux 45%
SiH2Ph
PhH2Si
SiH2Br
HBr 84%
SiH2Br
BrH2Si
(7)
(8)
SiH3
LAH 83%
SiH3
H3Si (1)
Scheme 1
Among the methods which can be employed to prepare tris"organosilyl#methanes the most straightforward one involves the MerkerÐScott procedure using magnesium or lithium reduction of halohydrocarbons and halosilanes in a polar solvent ð52JA1132\ 53JOC842\ 54JOM"3#87\ 69JOM"13#536Ł[ The reaction is usually performed by the addition of 0\0\0!trichloro! or tribromoalkane to a haloorganosilane "usually chlorotrimethylsilane# and Mg"Li# in THF[ In principle the synthesis provides a general route to symmetrically substituted tris"organosilyl#methanes\ but the correct choice of reagents and conditions is essential if good yields of pure compounds are to be obtained[ Experimental details for the preparation of tris"TMS#methane "2# from chloroform\ chloro! trimethylsilane and lithium metal are described in Inor`anic Synthesis "Equation "0## ð89IS128Ł[ A related preparation of the compound "Me1PhSi#2CH "69)# has been described starting from the corresponding chlorosilane\ bromoform\ and n!butyllithium ð74JCS"P1#618\ 82JOM"351#34Ł[ The trichloromethyl groups of a\a\a!trichloroethane ð52JA1132Ł\ 0\0\0!trichlorotoluene ð67CB2462Ł\ and a\a\a\a?a?a?!hexachloro!p!xylene ð56AG"E#831Ł can also be transformed into the tris"TMS#methyl groups[ Cl
TMS
TMS-Cl/Li
(1) Cl
Cl
THF, reflux 72%
TMS
TMS (3)
The reductive silylation was shown to tolerate an alkyne function[ Thus hexachlorobutyne!1 and
063
At Least One Metalloid or Metal
chlorotrimethylsilane react with lithium metal to furnish hexa"TMS#butyne!1 "8# in 47) yield "Equation "1## ð82JOM"351#20Ł[ Remarkably\ this compound\ owing to the steric shielding of the central p!system\ resembles trisilylmethanes in reactivity^ its C2C triple bond cannot be hydro! genated at 199>C:49 atm in the presence of a palladiumÐcharcoal catalyst[ Cl Cl Cl
Cl Cl Cl
TMS-Cl/Li THF, 20 °C
TMS TMS TMS
TMS TMS TMS
(2)
(9)
The partially alkylated halosilanes can also be used to obtain trisilylmethanes[ An example is the preparation of tris"dimethylsilyl#methanes "09# from dimethylchlorosilane and bromoform or a\a\a! tribromotoluene "Scheme 1#[ Bromination of silanes "09# and the subsequent reactions of the bromosilanes "00# with AgBF3\ t!butylamine\ and water illustrate the possible synthetic routes to Si!functionalized trisilylated methanes ð72JOM"141#170\ 82IC1297Ł[
Br Br
R
R
R
Me2SiHCl/Mg
Br
Br2
Si(H)Me2 Me2(H)Si Me2(H)Si (10)
THF, reflux
SiBrMe2 Me2BrSi Me2BrSi (11)
benzene, 5 °C
R = H, Ph AgBF4
(BrMe2Si)3CH
ButNH2 H2O
(FMe2Si)3CH (ButNHMe2Si)3CH (HOMe2Si)3CH
Scheme 2
A potentially very promising method for the build up of trisilylated C!0 units is the direct reductive silylation of carboxylic acid derivatives[ However\ whereas a!bis"TMS#alkanols can be readily obtained from esters using TMS!Cl:Na in THF ðB!70MI 595!90Ł\ attempts to realize the direct conversion of esters into trisilylated alkanes has so far had only limited success[ For example\ hexakis"TMS#!1!butene "01# could only be synthesized from dimethyl maleate in 0[4) yield "Equa! tion "2## ð82CB1116Ł[ O
O
TMS OMe
TMS-Cl/Mg/TiCl4
OMe
HMPA
TMS TMS (3)
TMS TMS
TMS (12)
HMPA = hexamethyl phosphoramide
For the synthesis of trisilylmethanes with di}erent silyl groups attached to the carbon atom the major synthetic pathway is a multistep reaction involving the interaction of a suitable Si!func! tionalized organometallic carbon nucleophile with a halosilane[ Scheme 2 illustrates this method! ology ð65JCS"D#1157\ 71CC0212\ 721AAC"386#10\ 74S606Ł[ Other typical examples are given in Schemes 3Ð 5 ð75CB0344\ 76AG"E#473\ 81ZN"B#794Ł[ Direct incorporation of a trisilylmethyl group into organic molecules may be achieved via organo! lithium or organomagnesium derivatives[ The organolithium reagents\ "R2Si#2CLi\ are available by metallation of tris"silyl#methanes with methyllithium in ether:THF ð69JOM"13#418\ 62JOM"44#198\ 72CC716\ 73JOM"158#106\ 75CC858\ 89IS128Ł\ but can also be generated at low temperatures from the tris"silyl#methyl halides and lithium metal or via the halogenÐmetal interconversion with phenyl! lithium "Table 0# ð75CC0932\ 81JCS"D#0904\ 81OM1827Ł[ Tris"TMS#methylmagnesium bromide is formed in 64Ð89) yields from "TMS#2CBr "in turn obtained by photobromination of neat "TMS#2CH at 079Ð089>C# and magnesium metal in diethyl ether ð81OM1827Ł[ Tris"TMS#methyllithium couples normally with methyl iodide to give the 0\0\0!tris"TMS#ethane[ Carbonylation leads to the acid "TMS#2CCO1H in 65) yield ð69JOM"13#418Ł[ The Grignard reagent
064
At Least One Metalloid TMS
i
Me4Si
Li (PMDETA)
iii
TMS
ii
ii
TMS
TMS
MgCl
Cl
TMS v
iv
TMS TMS
TMS
Cl
TMS
vi
Li (HMPA)
TMS
Li (TMEDA)
vii
vii
TMS TMS
TMS
TMS
vii
Li (THF)
TMS
SiR3
Reagents: i, BunLi/PMDETA, hexane, 20 °C; ii, TMS-Cl, hexane/ether; iii, Mg, ether, 20 °C; iv, ButLi/HMPA, THF, –40 °C, 5 h; v, BunLi/TMEDA, hexane, 25 °C, 12 h; vi, Li, ether, reflux, 24 h; vii, Me2PhSiCl, THF, 20 °C. (PMDETA = pentamethyldiethylenetriamine) Scheme 3 TMS Li
i
2 TMS
TMS
TMS
H
TMS
ii
Si TMS
H
I
TMS
TMS
iii
Si
TMS
TMS
I
TMS
TMS
TMS Si
Si
TMS
TMS
TMS TMS
TMS
i, SiH2Cl2, ether/pentane, –78 °C, 66%; ii, I2, 100 °C, 24 h, 37%; iii, C10H8Li, THF, –78 °C, 40% Scheme 4 Br TMS
TMS
Li
BunLi ether, –78 °C
TMS
TMS
TMS
130 °C, 12 h 90%
i, MeLi ii, H2O
SiBrBut2 TMS
Si(H)But2
But2SiHF
THF/ether 97%
TMS
Br2
TMS
CCl4, 0 °C 95%
SiMeBut2 TMS
TMS
Scheme 5 TMS
TMS
TMS
N
ButLi
Si N TMS
Cl
pentane –78 °C
TMS
TMS
N
But Si
N
Li Cl
CF3SO2O-TMS
TMS
N Si N
But TMS Cl
TMS
TMS Scheme 6
a}orded 0\0\0!tris"TMS#!1!phenylethane "63)# when derivatized with benzyl chloride ð81OM1827Ł[ Other carbon electrophiles such as nonenolizable aldehydes\ ketones\ acid chlorides\ and epoxides react with "TMS#2CLi to give the functionalized silanes "Scheme 6# ð70JCS"P0#858Ł[ However\ the method is not completely general^ it is limited by the readiness with which "TMS#2CLi abstracts a proton\ if one is available\ rather than attacks a carbon ð63AG"E#72\ 66CB741\ 70JCS"P0#858Ł[
065
At Least One Metalloid or Metal Table 0 Preparation of trisilylmethyllithium species[
Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Substrate Rea`ent Reaction conditions Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * MeLi Et1O:THF\ re~ux\ 4 h 89IS128 "TMS#2CH MeLi THF\ re~ux\ 5 h 72CC0289 "Me1Ph#2CH "TMS#2CBr Li ether\ 19>C\ 0 h 81OM1827 PhLi ether\ 9>C\ 2 h 81OM1827 "TMS#2CBr "MeOMe1Si#2CCl BunLi THF\ −67>C 75CC0932\ 81JCS"D#0904 "MeOMe1Si#1"TMS#CCl BunLi hexane\ −67>C 81JCS"D#0904 n Bu Li THF:ether\ −099>C\ 0 h 74JCS"P1#0576\ 80JOM"394#038 "MeOMe1Si#"TMS#1CCl ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
MeOCH2Cl or MeOCH2CH2OCH2Cl 78–82%
OR TMS TMS
65%
TMS
TMS Br
Br
NBS
66%
TMS TMS TMS
TMS
BCl3 or ZnBr2
TMS TMS
74%
TMS
TMS TMS
TMS
Li O Ph
PhCOCl
TMS TMS
TMS
TMS
O-TMS
TMS
Ph
OH ethylene oxide
TMS TMS
90%
COR
PCC 95%
TMS
TMS TMS
TMS
R = H or OH Scheme 7
The reaction of tris"TMS#methyllithium with O!ethyl thioformate gave the stable aliphatic thio! aldehyde "02#[ This was reduced with sodium borohydride to give the corresponding thiol "03# "Scheme 7# ð76JA168Ł[
Li
TMS TMS + TMS
S OEt
S THF, –78 °C
NaBH4
16%
TMS
TMS TMS
HS
100%
TMS
(13)
TMS TMS
(14)
Scheme 8
Tris"TMS#methyl!substituted ethene "04# is reported to be obtained by the reaction of 0\1! dilithioðtetrakis"TMS#Łethane with paraformaldehyde[ The formation of the compound implies 0\1! dianionic rearrangement of the silyl group "Equation "3## ð78JA2637Ł[ TMS TMS Li
TMS TMS Li
HCHO THF 73%
TMS TMS TMS (15)
TMS (4)
066
At Least One Metalloid
A quite di}erent route to trisilylated methanes and their derivatives involves the use as substrates of low!coordinate silicon derivatives[ In principle the insertion of unsaturated silicon compounds of the type "X2Si#1C1SiR1 into a polar elementÐhydrogen bond provides a general approach to tris"silyl#methanes[ Since the silaethenes are initially obtained from polysilylated methanes\ this appears to be a circuitous technique[ However\ it does lead to the speci_c polyfunctional compounds which are di.cult to prepare by other reactions ð73JOM"162#030Ł[ Thus alcohols\ phenols\ thiols\ hydrogen halides\ and amines add to the silaethenes "05# and "06# to give the insertion products "Equation "4##[ Ionic reagents like PhSLi and "PhO#1P"O#OLi have been employed in these reactions with equal success ð70CB2407\ 73JOM"162#030Ł[ The 0\0!dimethyl!1\1!bis"TMS#silaethene also inserts into the a!CH bond of pyridine to yield the trisilylmethane "07# "Scheme 8# ð75JOM"204#8Ł[ For all these reactions a nucleophilic attack mechanism can be invoked[ TMS
Me Si X Me (16) X = TMS (17) X = But2MeSi
TMS X H
AH
Me Si Me A
(5)
AH = H2O, ROH, RSH, R2NH, HHal
TMS TMS TMS (16)
Me Si Me
δ–
+
TMS H
Me Si Me N δ+
N
Me
TMS
TMS
Si Me TMS –
Me Si Me
TMS
N+
N
(18) Scheme 9
The formation of trisilylmethane derivatives proceeds equally well when in situ generated sila! ethene is treated with a proton donor reagent ð73JOM"162#030\ 74CRV308\ B!78MI 595!90Ł[ For example\ trisilylated methanes "08# have been isolated in good yield from reacting tris"TMS#methylsilicon halides with methanolic sodium methoxide[ The reaction is believed to proceed through an elim! ination\ analogous to E1 eliminations of alkyl halides\ involving synchronous attack of MeO− at a TMS group\ liberation of X−\ and formation of the transient silaethene followed by addition of methanol across the C1Si bond "Scheme 09#[ The compounds "TMS#2CSiPhMeF and "TMS#2CSi! PhCl1 react analogously to give "TMS#1CHSiPhMe"OMe# and "TMS#1CHSiPhCl"OMe#1 ð67JOM"046#C49\ 79JOM"080#244Ł[ It should be noted that in contrast to the silicon species\ the ger! manium compounds "TMS#2CGeR1X undergo normal "though very slow# direct nucleophilic sub! stitution at germanium ð79JOM"191#046Ł[ TMS TMS TMS
MeOH/NaOH
TMS
SiR2X
R
MeOH
TMS
R
>60%
TMS
SiR2OMe
Si reflux
TMS
(19) R = Me or Ph, X = Cl, Br or I R = Ph, X = F Scheme 10
The ene reactions of silaethenes are also potentially useful for the preparation of functionalized trisilylmethanes[ Thus silaethene "05# reacts with isobutene at −09>C to give compound "19#[ A similar reaction occurs between "05# and other alkenes ð76ZN"B#0951Ł[ The rates of these reactions are sensitive to steric hindrance but even the sterically encumbered silaethene "06# still adds propene
067
At Least One Metalloid or Metal
and isobutene ð75CB0356Ł[ The ene reactions of silaethenes with carbonyl compounds containing a proton in the a!position such as acetone\ cyclohexanone\ or ethyl acetate are also potentially useful for the preparation of functionalized trisilylmethanes "Scheme 00# ð72AG"E#0994\ 75CB0356\ 75JOM"204#8\ 76ZN"B#0951Ł[
R
TMS X
ether –78 to 20 °C X = TMS
Me Si Me
Me TMS Me Si TMS
Me TMS Me Si TMS
(16)
Me
R = Me
Si
R
TMS
Me TMS
(20) O
(16) X = TMS (17) X = TBDMS
R ether, –78 °C
Me TMS Me Si O X R Scheme 11
"ii# Compounds with an Si2C function as part of one or more rin` systems These can be prepared by a variety of methods of which the main ones are] "a# reductive silylation of a halohydrocarbon with a suitable halosilane "the MerkerÐScott procedure#^ "b# metal!induced coupling of chloromethylchlorosilanes^ "c# reaction between a lithiated cyclic carbosilane and a silicon electrophile^ and "d# cycloaddition to multiple carbonÐsilicon bond bearing silicon substituents at the carbon atom[ Synthesis of the tricyclic carbosilane "11# was accomplished by preparing the cyclic carbosilane "10# and reacting it with bromoform and lithium metal "Equation "5## ð61ZAAC"289#046Ł[ A similar reductive silylation route with silane "12# gave the tetrasilabicycloð1[1[1Łoctane "13# "Scheme 01# ð61ZAAC"289#080Ł[ 0\2!Disilabicycloð0[0[9Łbutane "15# has been synthesized by a method involving the low temperature reaction of carbosilane "14# with butyllithium in THF "Scheme 02# ð70ZAAC"364#76\ 73JOM"160#096Ł[ From the trisilylmethane "16# tris"dimethylchlorosilyl#ethene results in a remarkable yield "×74)# presumably via a silacyclopropane intermediate "Scheme 03# ð66ZAAC"329#010Ł[ Me Me Me Si
Me
Si
Si Br Br Br Si
Me Me (21)
Me Me Si Me HCBr3/Li
Si
Me
Me Si
Me
Si
Si
Me Si
Si
Me
Me
Me (6) Si Me Me
(22)
Synthesis of cyclocarbosilanes including an Si2C unit from {{carbon anion|| precursors appears to be a generally applicable method that is primarily limited by the availability of suitable starting materials ð63TCC32Ł[ Typically a lithiated cyclocarbosilane is generated in solution and then treated with the appropriate silylating reagent[ For example\ the conversion of 0\2\4! trisilacyclohexane "17# into trisilylated derivative "18# has been achieved by lithiation with BunLi:TMEDA complex followed by treatment with a chlorosilane "Scheme 04# ð72ZAAC"386#10Ł[ Among the many reactions of unsaturated siliconÐcarbon compounds which lead to cyclo! carbosilanes\ several include photochemical or thermal generation of silaethenes and their sub! sequent conversion into cyclic compounds containing an Si2C unit[ Thus irradiation of a benzene solution of "29# with a high!pressure mercury lamp gave 0\1!disilacyclobutane "20# in 89) yield "Scheme 05# ð68JA0237\ 70JA1213Ł[ Both photolysis and thermolysis of bis"TMS#diazomethane produce a carbene which rearranges
068
At Least One Metalloid Br
Li
SiPhMe2
Li
SiPhMe2 SiPhMe2 Me Si SiPhMe2
MeSiCl3
SiPhMe2
ether, –10 °C
79%
SiMe2Br SiMe2Br Me Si SiMe2Br
Br2 CCl4, 30 °C 95%
Si Si
HCBr3
Me Si
THF, 0 °C 25%
Si
(23)
(24) Scheme 12
Cl TMS
Cl
BunLi
Cl SiMe2Cl
SiMe2Cl
TMS
THF/ether –100 °C
Me Me Cl TMS Si
Li
TMS Cl Si Me Me
(25) Me
Me Si TMS
TMS Si
Me Me (26) Scheme 13
Me2ClSi
SiMe2CHCl
Me2ClSi
Cl
Me BunLi
Me2ClSi
Me
Me2ClSi
Me Si
Me2ClSi
Cl
Me2ClSi
85%
Me2ClSi
Cl
–
ether/pentane –100 °C
(27)
Me Si
Cl
SiMe2Cl
Me2ClSi Scheme 14
Me
Me Si
Me Si Me
Si Me Me
BunLi/TMEDA hexane
Me
Me
Me Si
Si Me
Si Me Me
TMS-Cl
Me
Me Si Me
Me Si Me
Si Me
Li
TMS (29)
(28) Scheme 15
via methyl migration to silaethene Me"TMS#C1SiMe1[ The latter dimerizes to produce as the major products cis! and trans!0\2!disilacyclobutanes\ Me"TMS#C"SiMe1#1C"TMS#Me "35)# ð79JA0473Ł[ Decomposition of compound "21# in the gas phase at 349>C a}ords product "22# via the cor! responding silaethene "Scheme 06# ð79JOM"075#298Ł[ Unsaturated systems of the type a1b\ a0b1c\ and a1b0c1d often combine with the C\C! disilyl!substituted silaethenes to give ð1¦1Ł!\ ð1¦2Ł!\ and ð1¦3Ł!cycloadducts containing Si2C units
079
At Least One Metalloid or Metal Ph Si TMS Ph
TMS
TMS
hν
Ph •
benzene, 20 °C
Si
TMS
Ph
(30) TMS
TMS TMS
TMS 1/2
Ph
TMS
90%
1/2
Ph Si Si Ph
Ph Ph
Si
TMS
Ph Ph
•
Si
TMS
Ph TMS
(31) Scheme 16
Me TMS
SiPh2F
TMS
TMS
450 °C
TMS
Ph
Si
Ph
Si
TMS
Si TMS
Ph
Me (33)
(32)
Me
Scheme 17
ð73JOM"162#030Ł[ However\ practically all such reactions are only useful for speci_c derivatives or speci_c groups of compounds[ Characteristic examples are given in Scheme 07[ The review by Wiberg contains experimental details for the preparation of compounds "23#Ð"25# ð73JOM"162#030Ł[ R
R
R
R
Si Me TMS TMS Me (34)
TMS TMS (16)
N N
Me Si Me
N N TMS
Si Me
TMS Me (35)
Ph Z
Me Me
Si
TMS TMS
Z
Z = O-, N-TMS
Ph
(36)
Scheme 18
5[95[1[0[1 Functions bearing three borons Tri!coordinate boron compounds\ BX2\ have a formally vacant orbital in the valence shell and are isoelectronic with the corresponding carbocations\ ¦CX2[ For triorganoboranes\ BR2\ there is little possibility of populating this orbital by conjugative interaction "apart from hyperconjugation# with the substituents[ It is hardly surprising\ therefore\ that the simple tris"boryl#methanes such as HC"BH2#2 or HC"BMe2#2 are highly reactive\ unstable compounds[ This is also a major reason why
070
At Least One Metalloid
compounds of the type HC"BX1#2 that have actually been isolated\ have X groups in which a heteroatom capable of donating p!electron density is bound to boron[ The preparation and proper! ties of the species containing a B2C function vary a great deal with the structural type and character of substituents\ and they will therefore be discussed under these headings[
"i# Tris"dihaloboryl#methanes\ RC"BHal1#2 The homologous C"BHal1#nHal3−n "n 0Ð3# were observed in the reaction between various boron halides and carbon vapor generated from a carbon arc[ In this manner B1Cl3 a}orded a mixture of C"BCl1#3\ ClC"BCl1#2\ and Cl1C"BCl1#1^ and BCl2 yielded the last two compounds as well as Cl"Cl1B#C1C"BCl1#1[ Compounds ClC"BCl1#2 and Cl1C"BCl1#1 are thermally unstable above −19>C[ From the reaction of B1F3 and carbon vapor\ C"BF1#3 was only isolated in a small amount ð58JCS"A#0771Ł[ The method for synthesizing tris"dichloroboryl#methane "26# is the exchange reaction of tris! "dimethoxyboryl#methane with boron trichloride and a catalytic amount of lithium borohydride "Equation "6##[ Reaction conditions were found to be critical^ it is important that a large excess of boron trichloride be used and that the crude product be distilled rapidly\ since it is particularly unstable to be stored ð62IC1361Ł[ Reaction of structure "26# with boron tribromide failed to lead to pure tris"dibromoboryl#methane\ HC"BBr1#2\ but bromineÐchlorine exchange did occur and the HCB2 signal of HC"BBr1#2 appeared in the NMR spectrum ð61MI 595!90\ 62IC1361Ł[ B(OMe)2
(7)
31%
B(OMe)2
(MeO)2B
BCl2
BCl3/LiBH4(cat.)
BCl2
Cl2B (37)
There are several reports in the literature that the addition of boron halides across multiple bonds leads to 0\0!diboryl!substituted alkanes ð71HOU"02:2a#0\ 80CRV24Ł[ Thus\ diboron tetrachloride adds twice to alkyne giving CH"BCl1#1CH"BCl1#1\ and dehydroboration of alkynes with dichloroborane ethyl etherate "BHCl1=Et1O# in the presence of BCl2 yields `em!diboryl compounds RCH1CH"BCl#1 ð65JA0687Ł[ However\ despite many unique advantages associated with hydroboration and halo! boration\ the synthesis of 0\0\0!tris"dihaloboryl#alkanes via alkynes has not yet been realized[
"ii# Tris"dialkoxyboryl#methanes\ RC"B"OAlk#1#2 These compounds have also been called methanetriboronic esters[ The compound HC"B"OMe#1#2 is named in Chemical Abstracts as methylidynetrisboronic acid hexamethyl ester[ The preparation and properties of tris"dialkoxyboryl#methanes have been reviewed up to 0865 ð64S036\ B!66MI 595!90Ł[ Tris"dimethoxyboryl#methane "27# is readily available on a large scale by direct reaction of chloroform with dimethoxyboron chloride and lithium metal in THF "Equation "7## ð57JA1083\ 58JOM"19#08Ł[ The procedure has been described in detail^ the product is isolated by distillation ð64S036Ł[ 0\0\0!Trichloroethane and a\a\a!trichlorotoluene react analogously\ but attempts to condense polyhalomethanes with bis"dimethylamino#boron chloride\ ClB"NMe1#1\ have failed[ Cl Cl
B(OMe)2
ClB(OMe)2/Li
Cl
THF, –40 °C 25–35%
(8) B(OMe)2
(MeO)2B (38)
Transesteri_cation of structure "27# with ethylene glycol in THF precipitates cyclic boronic ester "28# "74)# ð64JA4597\ 65JOM"009#14Ł[ Similarly the cyclic boronic esters "39# and "30# were formed from the tris"dimethoxyboryl#methane and pinacol or 0\2!propanediol in the presence of a catalytic amount of boron tri~uoride etherate ð69JOM"13#152\ 63JOM"58#34\ 64JOM"82#10Ł[ These compounds
071
At Least One Metalloid or Metal
proved to be more stable than their acyclic analogues and better yields of products have been obtained from them in a wide variety of reactions ð64S036Ł[
O O B O
O B
O
O B
B O
O
O
B
B
O
O
B
O O
O
O
B
B O
(39)
O
O (41)
(40)
The transborylation reaction of tris"dimethoxyboryl#methane "27# with triethylborane in the presence of {{ethylborane|| provides a route to the only known 0\0\0!tris"dialkylboryl#methane "32#[ The initially formed mixed triborylmethane "31# undergoes transformation to the compound "32# on heating at about 099>C "Scheme 08# ð64LA0228Ł[ The full scope of this reaction\ however\ remains to be explored further[ B(OMe)2
BEt3/[>BH]
B(OMe)2
(MeO)2B
B(OMe)Et
BEt3/[>BH]
BEt2
B(OMe)3
Et2B
(38)
BEt2 BEt2
Et2B
(42)
(43)
Scheme 19
The alkylation of the anionic species derived from methanetetraboronic esters ð62JA4985Ł by alkyl halides was found to proceed readily\ but unfortunately the reaction leads to a mixture of monoalkylated and dialkylated derivatives\ as illustrated in Scheme 19 ð69JOM"13#152\ 64S036Ł[ Evi! dently the initially formed 0\0\0!triborylalkane "35# is able to transfer a dimethoxyboryl group to tris"dimethoxyboryl#methide ion "34#\ thus undergoing disproportionation[ Condensation of triborylmethide anions with aldehydes and ketones a}ords alkene!0\0!diboronic esters "37#\ pre! sumably via the unstable cyclic borate anion "36# "Scheme 10# ð69JOM"10#P5\ 63JOM"58#42Ł[ The reaction is a general one and tolerates other functional groups\ including a!chloro\ carbethoxy\ or tertiary amino substituents ð63JOM"58#52\ 64JOM"82#10\ 67JOC849\ 67JOM"041#0Ł[ (MeO)2B
B(OMe)2
(MeO)2B
B(OMe)2
Li
B(OMe)2
(MeO)2B
B(OMe)2
MeLi THF, –70 °C
(44)
R
RI
(MeO)2B
(45) R (MeO)2B
Li
B(OMe)2
(45)
B(OMe)2
–(44)
(46) R
RI
B(OMe)2
(MeO)2B
R B(OMe)2
R = Me, Et Scheme 20
OR Li (RO)2B
B(OR)2 B(OR)2
O B – OR
R1COR2 THF, –70 °C
R1
41–93%
B(OR)2 R2 B(OR)2 (47)
O B(OR)2 = B(OMe)2, B O
O
Scheme 21
,B O
B(OR)2
R2
B(OR)2 (48)
O ,B
R1
O
072
At Least One Metalloid
Finally\ it should be noted that metallation of triborylmethide anions with Ph2ECl\ where E Si\ Ge\ Sn\ or Pb\ provides a useful method for the synthesis of compounds Ph2EC"B"OR#1#2 ð58JA5430\ 62JA4985\ 62JOM"46#114\ 62JOM"46#120\ 63JOM"58#52Ł[
"iii# Boracycloalkanes involvin` a B2C function There are several speci_c methods which are useful for the preparation of boracycloalkanes containing a B2C unit[ Compounds "49# are obtained in up to 49) yield via the isolable 0\0!bis"dialkylboryl#!0!alkenes "38# from dialkyl"0!alkynyl#boranes and dialkylboranes "Scheme 11# ð53TL0556\ 64LA0228\ 73HOU"02:2c#051Ł[ These have been classi_ed as pentaalkyl!0\4!dicarba!closo!pentaboranes"4#\ but the valency requirements of all atoms can be satis_ed without the need to involve electron!de_cient bonding ð69JA3047\ 63JCS"D#554\ 80CB1534Ł[ R2
R12B
R12B
HBR12
R2
5 °C
R2
HBR12
R1
B R1
B B
R1
2B
R1
(49)
R2
R1 = Me, Et, or Pr R2 = H, Me, or C6H13
(50)
Scheme 22
An e.cient synthesis of 1\2\4\5!tetraborabicyclo ð1[0[0Łhexane "40# utilizes the reaction of 0\0\1\1! tetrakis"chloro"diisopropylamino#boryl#ethane with sodium:potassium alloy in benzene "Equation "8## ð89AG"E#181Ł[ R
R R R Cl
B
B Cl H B Cl
H Cl
B
B
R
Na/K
R R
B B
benzene, reflux 73%
B
R = Pri2N
R (51)
(9)
Sealed!tube pyrolysis of BMe2 permits isolation of 1\3\5\7\8\09!hexaboraadamantane "41# in 14) yield ð62CC421\ 64JCS"D#037Ł[ This boronÐcarbon cage compound appears to be unique in having a stoichiometry expected of a carborane and yet not possessing the usual carborane type of structure ð66JCS"D#025Ł[ The ethyl analogue "42# is produced by thermal decomposition of the tris! "diethylboryl#methane or polyboryl compounds\ themselves obtainable by hydroboration of dial! kyl"alkynyl#boranes ð64LA0228Ł[ R
R B
R
B B B R
R
B R
B
(52) R = Me (53) R = Et (54) R = But (55) R = Cl (56) R =Br (57) R = Me2N
Pyrolysis of alkyldichloroboranes such as MeBCl1\ Cl1BCH1CHBCl1 or "Cl1B#2CH at 349>C forms hexachlorohexaboraadamantane "44# "4Ð17)#[ The synthesis of hexabromohexabora! adamantane "45# has been achieved by heating Me1BBr or MeBBr1 to 419>C[ The reactions of structure "44# with t!butyllithium and diethylamine at −59>C lead to the formation of the cor! responding t!butyl! "43# and dimethylamino! "46# derivatives ð78JOM"256#08Ł[ Another route to compounds possessing C3B5Ðadamantane structure uses dimerization of the C1B2!closo!carbaborane "49# by treatment with potassium followed by iodine "Equation "09## ð74AG"E#215Ł[
073
At Least One Metalloid or Metal Et Et
B
Et B
2K/I2
B Et B
B
(10)
B
THF, 20 °C, 4 d 27%
Et
B Et
B
B
Et
Et
(50)
(58)
The formation of compounds C5H8=x"BNPri1# "x 0Ð5# from the reaction of benzene with dich! loro"diisopropylamino#borane and sodium:potassium alloy in 0\1!dimethoxyethane has been con! _rmed by mass spectroscopic studies[ The compound with x 2 was separated from the reaction mixture and identi_ed as 1\7\8!triborabicycloð2[2[0Łnona!2\5!diene!1\7\8!triamine "48# "Equation "00## ð77JOM"236#00Ł[ Similarly\ 0\3\5!triboraspiroð3[3Łnona!1[7!diene "59# has been isolated from the reaction of benzene with subvalent boron species ð89CC630Ł[
Pri2N
B
B
NPri2
B NPri2 (59)
2n Na/K n Cl2BNPri2
(11)
C6H6•xBNPri2
10n –2n MICl (DME)
Pri2N B B
B NPri2
Pri2N (60)
Addition of a mixture of bis"TMS#butadiyne or 1\4!dimethyl!1\3!hexadiene with Pri1NBCl1 to Na:K alloy in hexane gave the 1\3\4!triborabicycloð0[0[0Łpentane "23)# "Equation "01## ð81CB0796Ł[ TMS Pri2N BNPri
Na/K,Cl2
TMS
2
TMS hexane, RT
TMS
B NPri2 B NPri2
(12)
A unique method for the synthesis of compounds containing a B2C function utilizes low!coor! dinate boron derivatives[ 1!Boranediyl!0\2!diboretanes "50# smoothly add ethanol to give com! pounds of structure "51# in quantitative yields "Equation "02## ð78AG"E#670Ł[ Despite considerable synthetic potential\ this method is clearly limited by the availability of the requisite boron substrates[ Ar TMS
Ar
B
EtOH
TMS
B
Ar
100% (NMR)
TMS
B
OEt
(13)
B Ar TMS
B Ar (61)
Ar (62) Ar = 2,4,6-Me3C6H2, 2,3,5,6-Me4C6H
074
At Least One Metalloid 5[95[1[0[2 Functions bearing three germaniums
In contrast to numerous publications dealing with trisilylmethanes\ literature reporting tri! germylmethyl derivatives are sparse[ It is curious that straightforward synthetic routes are known for compounds containing Si2C functions but not for those with functions bearing three germaniums[ It appears that many of the methods suitable for the synthesis of mono! and bisgermylalkanes are ine}ective or not applicable to trigermylmethanes[ For example\ although the compound "Et2Ge#1CH1 was successfully obtained by the reaction of triethylgermylpotassium with dichloromethane\ attempts to prepare "Et2Ge#2CH by a similar route have failed\ because the metalÐhalogen exchange reaction\ followed by conden! sation\ predominated ð56TL0332Ł[ The reaction of Ph2GeNa with chloroform in liquid ammonia was also unsuccessful[ Only one of the three chlorine atoms bonded with a carbon is quantitatively replaced by the Ph2Ge group^ a second chlorine is largely substituted while the third is completely replaced by hydrogen ð21JA0511\ 41JA0307Ł[ The _rst stable compound with a Ge2C function\ 0\4\4\4!tetrakis"trimethylgermyl#!0\2!pentadiyne "53#\ has been synthesized by condensation of the tetralithium compound from 0\2!pentadiyne with chlorotrimethylgermane "Scheme 12# ð62JA2213Ł[ Reaction leads to a mixture of two pergermylated isomers\ "52# "31)# and "53# "06)#\ which were separated by preparative gas chromatography[ The method is only of limited value\ since polylithiated species are not readily available[ BunLi/TMEDA
Me3GeCl
C5Li4
THF
n-butane
GeMe3 GeMe3
+
Me3Ge
GeMe3 GeMe3
Me3Ge
• Me3Ge
GeMe3 (63)
(64) Scheme 23
0\0\0!Tris"triethylgermyl#acetone was reported to form in very low yield from the reaction of triethylgermyldiazoacetone with an equimolar amount of bis"triethylgermyl#mercury in the presence of metallic copper ð66JOM"031#044Ł[ Although this transformation is of some mechanistic interest\ it does not provide a synthetically viable route to trigermylmethyl species[ The more ~exible and useful route to 0\0\0!trigermylalkanes involves stepwise base!assisted introduction of an R2Ge group into compounds containing an activated methyl group[ Sato and co! workers have prepared a series of trigermylacetic acid derivatives using this approach ð77JOM"243#044\ 77OM628\ 89OM0214Ł[ Some of these reactions are outlined in Schemes 13\ 14\ and 15[ The reaction of the lithium salt of trimethylgermylacetonitrile with bromotrimethylgermane is not straight! forward and leads to a mixture of germylated species "Scheme 13#[ Detailed investigation showed that the trimethylgermylacetonitrile anion readily reacts with Me2GeCH1CN via intermolecular anionic rearrangement of the Me2Ge group to give bis"trimethylgermyl#acetonitrile anion and MeCN[ Anion "Me2Ge#1C−CN\ prepared from structure "55# with an equimolar amount of lithium diisopropylamide "LDA#\ is stable enough at low temperature[ However\ treatment of "55# with a 9[4 molar equivalent of LDA gives a mixture of germylated products ð76SC0162Ł[ i, 2 BunLi ii, 2 Me3GeBr
Me3GeBr/Zn
Cl
CN
Me3Ge
benzene/THF 71%
ether, –78 °C
(65)
CN
NC
+ GeMe3
Me3Ge
CN
(66)
Me3Ge
GeMe3 GeMe3
(67) Scheme 24
Trimethylgermylation of ethyl lithioacetate gave a high yield of ethyl"trimethylgermyl#acetate "57#[ The use of excess amounts of LDA and Me2GeCl a}orded ethyl tris"trimethylgermyl#acetate "58# in high yield "Scheme 14# ð77OM628Ł[ Under approximately the same conditions\ the tris! "trimethylgermyl#acetamide "69# has been obtained in 61) yield "Scheme 15# ð77JOM"243#044Ł[
075
At Least One Metalloid or Metal i, LDA ii, Me3GeCl
O
i, 2 LDA ii, 2 Me3GeCl
MeCOOEt
Me3Ge
ether, –78 °C 78%
Me3Ge
COOEt THF –78 °C 82%
Me3Ge
(68) Scheme 25
i, 2 LDA ii, 2 Me3GeCl
O
GeMe3
N
N
Me3Ge
THF –78 °C 82%
i, BunLi ii, Me3GeCl
Me3Ge
0 °C, 72%
Me3Ge
O
OEt GeMe3 (69)
GeMe3 N O (70)
Scheme 26
The LAH reduction of structure "58# gave a 67) yield of 1\1\1!tris"trimethylgermyl#ethanol\ and treatment with n!butyllithium at room temperature a}orded an 75) yield of 0\0\0!tris! "trimethylgermyl#!1!hexanone ð77OM628Ł[
5[95[1[0[3 Functions bearing mixed metalloids Several procedures are available for the synthesis of compounds of the type RC"E0Xm#! "E1Xn#"E2X"m#n#\ where E0\ E1\ and E2 Si\ B\ or Ge\ but two groups of reactions are most important[ The _rst group includes the reactions of organometallics RC"M#"E0Xm#"E1Xn# with inorganic or organoelement halides\ Xm"n#E2Hal\ and the second is the reactions based on unsatu! rated germanium or boron compounds containing elementÐcarbon double bond\ XmE0 C"E1Xn#"E2Xm"n##[
"i# Synthesis based on a!silyl!\ boryl!\ or `ermyl!substituted or`anometallics Three typical examples illustrating this methodology are shown in Equations "03#Ð"05# ð65JOM"009#14\ 67JOM"042#142\ 78AG"E#44Ł[ The requisite organometallics can be obtained by methods which are discussed in Section 5[95[1[1[ MgCl TMS
TMS
ether, 80%
(14) TMS
TMS
TMS
Li
BCl3
TMS
TMS
GeCl3
GeCl4
ether, 20 °C 38%
TMS
TMS B TMS
Cl
Li O
(15)
GePh3
B
B
O
O
O
Ph3GeCl ether, 20 °C 42%
O
B
B
O
O
O
(16)
In principle\ the approach provides a general synthetic pathway to compounds containing mixed metalloid functions\ but the correct choice of the reactants and reaction conditions is very important[ The best results were obtained by the low temperature reaction of a functionalized organolithium or organomagnesium compound with a metalloidal halide in ethereal or THF solution[ The group on metalloid which is usually replaced includes Cl\ F\ RO\ or "TMS#1N ð75CB1855\ 78CB0946\ 80POL0042Ł[ Germanium chlorides react with a!silylated organometallics with retention of the oxidative state of germanium[ For example\ treatment of GeCl1"diox# or Ge"N"TMS#1#1 with an equimolar amount of MgCl"CH"TMS#1# or Mg"CH"TMS#1#1 in ether leads to the bis"bis"TMS#methy#lgermylene "60# in 59Ð69) yield "Equation "06## ð65CC150\ 65JCS"D#1157\ 71CC0396\ 73CC379\ 75JCS"D#0440Ł[ The related preparation of bis"TMS#methyl"pentamethylcyclopentadienyl#germylene "61# has been described
076
At Least One Metalloid
starting from Me4C4GeCl and "TMS#1CHLi "Equation "07## ð75OM0833Ł[ It should be noted that bis"TMS#methyl!substituted germylenes such as structures "60# and "61# and "TMS#2CGeCH"TMS#1 ð80OM0536Ł represent a unique class of compounds\ which can exist as monomers "carbene ana! logues# or dimers "alkene analogues# depending on the structure and phase state ð80CRV200Ł[ If an electrophile such as iodine\ methyl iodide\ acetyl chloride\ a diazoalkane\ or a diazidosilane is added to the germylene "61#\ then high yields of the oxidative addition products containing the Ge"IV#CH"TMS#1 unit are obtained ð75OM629\ 83OM323\ 83OM325Ł[ A reaction of germylene "60# with an alcohol provides the functionalized germane HGe"CH"TMS#1#1OEt ð70JOM"101#C3Ł[ [(TMS)2CH]2Mg
GeCl2(diox)
TMS
(TMS)2CHLi
TMS (17)
ether, 60–70%
Me5C5GeCl
Ge
TMS TMS (71) Me5C5Ge
TMS (18)
benzene/ether –80 °C, 76%
TMS (72)
"ii# Synthesis based on low!coordinate boron and `ermanium derivatives C\C!Disilyl!substituted methyleneboranes\ XB1C"TMS#1 ð82AG"E#874Ł\ and germaethenes\ X1Ge1C"SiR2#1 ð73JOM"162#030\ 89CRV172Ł\ provide access to a variety of compounds containing mixed metalloid functions\ but the scope of the reactions is restricted to the preparation of speci_c polyfunctional compounds[ At a temperature of 499Ð599>C methyleneboranes "62# and "63# undergo rearrangement into cyclic compounds in excellent yield ð89CB636Ł[ In analogous conditions the methyleneborane "64# is transformed to an azasilaboratedine "Scheme 16# ð78CB484Ł[ Me 560 °C
B
R = Ph, 79%
Si
TMS Me
TMS
580 °C
TMS
R = PhCH2, 92%
Me
B
Me
B R
TMS
Si Me
Me
(73) R = Ph (74) R = PhCH2 (75) R = Pri2N Me
Pri 520 °C
N Si Me B
R = Pri2N, 46%
Me
TMS
Scheme 27
Treatment of the trisilyl"germyl#methane "65# with CsF in DIGLYME leads to a compound of structure "67#[ The reaction is believed to take place by initial formation of the unstable germaethene "66#\ which because of steric hindrance\ cannot undergo cyclodimerization and looses a TMS group to give a second transient germaethene "Scheme 17# ð72IZV848Ł[
TMS TMS
GePh2Cl TMS (76)
CsF DIGLYME 48%
TMS TMS
TMS
Ph Ge Ph (77) Scheme 28
Ph Ge Ph
Ph
Ph Ge
TMS
TMS Ge Ph Ph (78)
077
At Least One Metalloid or Metal
A variety of disilyl"boryl#methanes has been prepared by making use of the high reactivity of the B1C double bond towards protic agents and organolithium compounds ð82AG"E#874Ł[ Some of these reactions are outlined in Scheme 18 ð76CB0958\ 78CB484Ł[ Borinanes "79# were obtained from the addition of HCl or HN"TMS#1 to the B1C bonds of boranediylborinanes "68# "Equation "08## ð81AG"E#0273Ł[ A related preparation of the 0\2!diboretane "71# has been described starting from germaethene "70# "Equation "19## ð76AG"E#687Ł[ Pri2N
HX
TMS B
X = Hal, RO, R2N
X
TMS
TMS B Pri2N
TMS
i, MeLi/TMEDA ii, H+
Pri2N
hexane, –78 °C 79%
Me
TMS B TMS
Scheme 29 R B B
R
R
B
HX
TMS
(19)
TMS
TMS (79)
B(X)R
TMS (80) R = But, 2,3,5,6-tetremethylphenyl X = Cl, (TMS)2N R
R TMS
B
TMS
B
X Ge X
HCl
TMS
B
TMS
B
GeX2Cl
(20)
R (82)
R (81) R = But, X = (TMS)2N
Germaethene "72# generated as a reaction intermediate by thermal elimination of LiCl from Me1ClGe0C"Li#"TMS#1\ can be converted into various compounds containing an Si1"Ge#C function and in some cases this provides the best route to the new species "Scheme 29# ð75CB1855\ 75CB1879\ 76CB0192Ł[ Compound "74# has been synthesized by a method involving the low temperature reaction of kinetically stabilized germaethene "73# with methanol "Equation "10## ð80POL0042Ł[ TMS TMS
TMS
OMe TMS
TMS MeOH
Ge
Ge TMS
TMS TMS (84)
TMS TMS
ether, –20 °c 81%
(21) TMS TMS
(85)
"iii# Miscellaneous 0\2!Digermacyclobutane "75# has been found among the products of {{direct synthesis|| from TMS"dichloromethyl#silane "Equation "11## ð61ZOB0410Ł[ The reaction of 0\2!diborete "76# with potassium or lithium in THF leads to compounds 1K¦"76#1− or 1Li¦"76#1−\ which are protonated with "TMS#1NH to yield the 0\2!diboretane "77#[ Reaction of "76#1− with MeI a}ords the 0\2! diboretane "78# "Scheme 20# ð78CB0770Ł[ Cl Cl
Cl Ge
"Ge/Cu"
TMS Cl
TMS
370–390 °C 4%
TMS Ge Cl
Cl (86)
(22)
078
At Least One Metalloid TMS Me2Ge
TMS MeO
TMS OMe
TMS OMe
MeOH
R
TMS Me Ge Me TMS (83)
R
R (R = H, Me, CMe=CH2)
TMS
TMS
Me2Ge
TMS
Me2Ge
TMS
R
R
Scheme 30 R 2N TMS
TMS
B Cl
TMS
2K
B TMS
THF
B Cl R2N
2M+ (87)2–
NR2
R2N (87)
TMS
2M
B THF
TMS
TMS
TMS B
B
(TMS)2NH
(87)2–
2 MeI
NR2
R2 N
B
(88)
B NR2
R2 N (89) Scheme 31
5[95[1[1 Functions Containing Metalloids and Metals 5[95[1[1[0 Functions bearing silicon"s# and metals"s# This section is devoted to methods of preparing a!silylated organometallics having the general structure RC"SiX2#n"MLm#2−n\ where M is a metal\ n 0 or 1\ and R H\ alkyl\ aryl\ or hetaryl[ These compounds are of special interest due mainly to _ndings that silylmethyl groups like "TMS#1CH or "TMS#2C combine bulkiness with the capability to form strong metalÐcarbon bonds and that organometallic compounds bearing the polysilylmethyl group often possess unique proper! ties and have unusual structures ðB!74MI 595!90\ B!80MI 595!90Ł[ Although a!metallated organosilane chemistry has been reviewed extensively since the early 0879s ð79HOU"02:4#16\ B!70MI 595!90\ B!72MI 595!90Ł\ polysilylated organometallics have received only passing comment within reviews with much wider scope ðB!74MI 595!90\ 80COS"0#0Ł[
"i# Alkali metal and ma`nesium derivatives of silylmethanes In the mid 0889s there are four general methods for the production of compounds of this type[ These are] "a# metalÐhydrogen exchange reactions of silylmethanes with basic metal!containing reagents^ "b# oxidative metallation of halo"silyl#methanes^ "c# organometallic addition to vinylsilanes^ and "d# transmetallation of an already a!metallated organosilanes[ Representative examples illustrating the synthesis of alkali metal and magnesium derivatives of
089
At Least One Metalloid or Metal
silylmethanes which have obvious potential synthetic utility are given in Table 1[ A few of the silylmethyl derivatives of the alkali metals display unique aggregate structures and these are discussed by Williard ð80COS"0#0Ł[ Table 1 Preparation of trisilylmethyllithium derivatives of the alkali metals and magnesium[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Compound Method of preparation Reaction conditions Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * t "TMS#1CHLi "TMS#1CH1 ¦Bu Li THF:HMPA "ca[ 3 ] 0#\ 66CB741\ 79JA0473 −67>C "TMS#1CHLi "TMS#1CH1 ¦BunLi¦TMEDA hexane\ 01 h\ 14>C 71CC0212 "TMS#1CH1 ¦BunLi¦PMEDA hexane\ 9[4 h\ 19>C 71CC0212 "TMS#1CHLi "TMS#1CHLi "TMS#1CHCl¦Li ether\ re~ux 65JCS"D#1157\ 79JA0473 "TMS#2CH¦MeOLi HMPA\ 19>C 62TL3082 "TMS#1CHLi "TMS#"MeOMe1Si#CHLi "TMS#"MeOMe1Si#CH1 ¦ButLi pentane\ 19>C 78JOC0673 "TMS#1CHR¦BunLi THF:hexane 75CC561 "TMS#1CRLia a n "TMS#1CRLi "TMS#1CHR¦Bu Li¦TMEDA hexane 73CC0697 "TMS#1CRLia "TMS#1CHR¦BunLi hexane:ether\ 19>C\ 0 h 72CC0308\ 73CC0697 "TMS#1CHR¦BunLi¦TMEDA hexane\ 19>C 73JCS"D#0790 "TMS#1CRLib "TMS#1CHNa "TMS#2CH¦NaOMe HMPA\ 19>C 62TL3082 "TMS#1CHLi¦ButOK hexane\ 19>C\ 05 h 80OM0693 "TMS#1CHK "TMS#1CHCl¦Mg ether\ re~ux\ 3 h 80JOM"310#064 "TMS#1CHMgCl ð"TMS#1CRŁ1Mga "TMS#1CHR¦MgBunBus heptane 75CC561 TMSCHBr1 ¦Mg"Hg# diisopropyl ether 75TL5012 TMS!CH"MgBr#1 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a
R 1!pyridyl[
b
R 3!methylphenyl[
"a# MetalÐhydro`en exchan`e[ The methylene group between two silicon atoms shows enhanced reactivity with respect to proton abstraction by strong bases\ therefore many bis"silyl#methanes undergo metalÐhydrogen exchange on reaction with alkyllithium reagents ð66CB741\ B!72MI 595!90\ 72ZAAC"386#10Ł[ In practice\ these reactions require strongly coordinating solvents or the use of alkyllithiums in the activating presence of TMEDA or potassium t!butoxide[ The successful prep! aration of bis"TMS#methyllithium can be achieved from the bis"TMS#methane using t!butyllithium in hexamethylphosphoramide "HMPA# ð62TL3082\ 63AG"E#72Ł\ t!butyllithium in THF with HMPA at −67>C ð66CB741\ 79JA0473Ł\ BunLi:ButOK reagent in THF solution ð80OM440Ł or the TMEDA complex of n!butyllithium in hexane ð71CC0212Ł[ The last procedure provides one of the simplest routes to "TMS#1CHLi[ In addition\ a feature of the use of TMEDA is that it enables crystalline monomeric lithium derivatives to be isolated[ Silylated product yields for the system TMS! CH1TMS:BunLi:ButOK were in the range 67Ð80) ð80OM440Ł[ Metallation of the carbosilane "TMS#1CHSiMe1CH1TMS gave\ as expected\ "TMS#1C"Li#SiMe1CH1TMS\ since the indicated car! banion is stabilized by three silyl groups[ Only monometallation could be achieved for the carbosilane TMS!CH1SiMe1CH1SiMe2 ð80OM440Ł[ Poly"dimethylsilene#\ "Me1SiCH1#n\ the poly! mer formally derived from dimethylsilaethene\ Me1Si1CH1\ has been shown to be metallated by BunLi:ButOK in THF to give a polycarbosilane in which\ on average\ every fourth CH1 group in an SiCH1Si environment is metallated ð80OM440Ł[ Methoxydimethylsilyl"TMS#methyl lithium\ HC"Li#"TMS#SiMe1OMe\ a reagent useful for the direct conversion of aldehydes and ketones to vinylsilanes\ is readily formed in hydrocarbon solvent from the appropriate silane and t!butyllithium ð78JOC0673Ł[ Access to the p!xylene compound p! MeC5H3CH"TMS#1Li is possible by using BunLi:TMEDA in hexane ð73JCS"D#0790Ł[ However\ organolithium tertiary amines reagents failed to yield the dilithium derivative from 0\3!bis"bis! "TMS#methyl#benzene ð73JCS"D#0790Ł[ Lithium t!butylbis"TMS#acetate\ "TMS#1C"Li#CO1But\ results from the appropriately substituted acetate using LDA in THF at −67>C ð65TL1626\ 66JOC1927Ł[ This organolithium compound is a useful synthetic intermediate in the Peterson alkenation reaction ðB!72MI 595!90Ł[ Reaction of the pyridine functionalized bis"TMS#methane "89# with n!butyllithium in hexane yields complex "80#\ whereas metallation of "89# with BunLi and TMEDA in hexane a}ords lithium derivative "81#[ Both compounds contain unprecedented h2!azaallyl ligand geometries ð73CC0697Ł[ Treatment of 1!bis"TMS#methylpyridine with BunLi in ether or THF yields binuclear complex "82# "Scheme 21# ð72CC0308Ł[ A procedure for the preparation of 1!lithio!0\0\2\2\4\4!hexamethyl!0\2\4!trisilacyclohexane by the metallation of cyclo!ðMe1SiCH1Ł2 with BunLi:TMEDA in hexane has been developed ð72ZAAC"386#10\ 81OM2353Ł[ The yields of monolithium derivative in this synthesis is very good\ but further met! allation did not occur at 19>C even when excess metallation reagent was used[ Similarly 0!TMS! 0\2\4!trisilacyclohexane can be selectively metallated at the more sterically available ring proton^
080
At Least One Metalloid
BunLi in hexane 20 °C
N
TMS
:
N
Li TMS
CH(TMS)2
(TMS)2HC
(90)
BunLi in hexane, 20 °C + TMEDA
(91)
BunLi in ether 20 °C, 1 h
ether, 20 °C
TMS N
TMS
N
TMS
:
Li Li
Me2N
TMS NMe2
Li
TMS
N
TMS
(92)
(93) Scheme 32
however\ if not immediately quenched the kinetic product "83# rearranges to the more stable lithium derivative "84# "Scheme 22# ð72ZAAC"386#10Ł[ In contrast to 0\2\4!trisilacyclohexane\ 0\0\2\2! tetramethyl!0\2!disilacyclobutane "85# reacts with n!butyl\ methyl!\ and phenyllithium to open the Si1C1 ring ð64JCS"D#0323\ 89OM1566Ł[ Even so\ the solutions of 1!lithio!0\2!disilacyclobutane "86# could be prepared by the action of ButLi:TMEDA on "85# in hexane "Scheme 23# ð89OM1566Ł[ In reactions of "86# with TMS!Cl\ Me1HSiCl\ Me2SnCl\ n!PrI\ XCH1CH1X "X Br\ I#\ Me1S1\ and I1\ the disilacyclobutane ring is retained while the methylene carbon atom is functionalized ð89OM1566Ł[ Li Si
BunLi/TMEDA
Si Si
TMS
hexane, 20 °C
Si
Si
Si
Si Li
Si
TMS
Si
(94)
TMS
(95)
Scheme 33
MeLi ether, reflux >74%
Me2Si
TMS Li Si Me Me
SiMe2 Li (96)
ButLi/TMEDA hexane >60%
Me2Si
SiMe2 (97)
Scheme 34
"b# Oxidative metallation of halo"silyl#methanes[ This is a superior method for generating a variety of silyl!substituted organometallics from readily available starting materials[ The synthesis is very simple to carry out in the laboratory and yields are normally excellent[ For example\ chlorobis"TMS#methane reacts with lithium metal in ether to give the corresponding lithium deriva! tive in virtually quantitative yield ð65JCS"D#1157Ł[ The starting functionalized methane may be readily prepared from CH1Cl1\ TMS!Cl\ and BunLi as shown in Scheme 24 ð60JOM"18#278\ 70SRI480Ł[ In the opinion of the present authors\ this route is best for the preparation of "TMS#1CHLi[ One limitation of this scheme is that the synthesis of compounds "TMS#1C"R#Li is di.cult or impossible if group
081
At Least One Metalloid or Metal
R is methyl or primary alkyl[ Thus the reaction of "TMS#1C"Me#Cl with lithium metal leads to "TMS#1C1CH1 and "TMS#1C"H#Me instead of the expected lithium species ð68ZAAC"337#39Ł[ BunLi
Cl
Cl
THF/Et2O/penatne –110 °C
Li
TMS
Cl
Cl
BunLi
+ 2 TMS-Cl
Cl
Cl
EtOH
TMS
TMS
–100 °C 78%
TMS
TMS Li
Li
TMS
ether, reflux
TMS
TMS
Scheme 35
The preparation of bis"TMS#methylmagnesium halides can be performed in ether or THF using halobis"TMS#methane and magnesium powder ð72POL180\ 75JCS"D#0440\ 80JOM"310#064Ł[ The method can be extended to the preparation of bis"metallated# silylmethanes[ Thus\ dili! thio"TMS#methane "87# was obtained by reaction of dichloro"TMS#methane with lithium vapor "Equation "12## ð73CC0553Ł[ It should be noted that an alternative approach to this compound is the thermolysis of TMS!CH1Li ð77POL1912Ł[ The bulky TMS groups seem to prevent extensive polymerization of the dilithium derivative[ In both preparations the only by!products were lithiated methanes and silanes[ No higher polymers such as those observed for "CH1Li1#n were seen ð73CC0553Ł[ Cl
Li
Li (vapour)
(23) TMS
Cl
700–720 °C 10-4 Torr
TMS Li (98)
Bis"bromomagnesio#TMSmethane "88# has been prepared directly from the reaction of TMS! CHBr1 and magnesium amalgam in diisopropyl ether "69)# "Equation "13## ð75TL5012Ł[ In relation to CH1"MgBr#1\ compound "88# is less reactive^ this must be due to the anion!stabilizing e}ect of the TMS group and possibly to steric hindrance[ Br
MgBr
Mg/Br
(24) TMS
Br
Pri2O, 20 °C
TMS MgBr (99)
"c# Or`anometallic addition to vinylsilanes[ While organolithium compounds and Grignard reagents will not\ in general\ add to isolated C1C double bonds\ they will add to the silyl!substituted alkenes to form a!silyllithium or a!silylmagnesium derivatives ð41JA3471\ 43JOC0167\ 69CJC450\ 69TL0026Ł[ The examples provided in Scheme 25 illustrate the application of the method for the synthesis of lithiated bis"silyl#methanes[ Compounds of structure "099# are prepared in more than 89) yield ð63AG"E#72Ł[ The a!lithio derivative "090# can be trapped by trimethylsilyl tri~ate to give compound "091#\ and is a useful silaethene precursor "Scheme 25# ð81ZN"B#794Ł[ Li
TMS
TMS
TMS
CH2O
TMS
RLi
TMS
Li
TMS
TMS
R (100)
R = Bun, Bus, or But TMS TMS
TMS TMS ButLi
Cl TMS
pentane, –78 °C
Li
TMS TMS But
CF3SO2O-TMS
But TMS
Cl
Cl
TMS (101)
TMS (102)
Scheme 36
It has been established\ by analogy to 0\0!bis"TMS#ethenes\ that silaethenes\ germaethenes\ and their analogues add organolithium reagents to form the appropriate polyfunctional derivatives
082
At Least One Metalloid
ð73JOM"162#030\ 74OM228\ 80AG"E#82Ł[ For instance\ the lithium species "093# was generated as shown in Scheme 26 by addition of phenyllithium to a solution of stannaethene "092# ð80AG"E#82Ł[ Me
TMS
PhLi
TMS
hexane, –78 °C
Me2PhSn
Sn Me
TMS
(103)
Li
SnPhMe2
MeOH
TMS
TMS
TMS
(104) Scheme 37
0\1!Dilithio"tetrakis"TMS##ethane "094# results directly from the reaction of tetrakis"TMS# ethylene with excess lithium metal in dry!oxygen!free THF "Equation "14## ð78JA2637Ł[ The structure of "094# has been unequivocally con_rmed by x!ray crystallography and chemical transformations[ Treatment of the dilithium compound with H1O and D1O cleanly produced tetrakis"TMS#ethane "095#[ The reaction with paraformaldehyde a}orded alkene "096# "62)# probably via 0\1!anionic rearrangement of the silyl group "Scheme 27#[ After prolonged standing "8 days#\ quenching the THF solution of "094# with water led to the formation of compounds "097# and "098# together with small amounts of cyclic compounds "009# and "000# "Scheme 28# ð82CL156Ł[ These reactions probably involve intramolecular proton abstraction from a methyl group on silicon followed by subsequent anionic rearrangement[ THF TMS
TMS
TMS
TMS
2Li
TMS
Li
TMS
THF
TMS
Li
TMS
(25) THF (105)
TMS TMS TMS TMS X X (106)
X2O (X = H, D) THF, –78 °C
(105) TMS
TMS
HCOH
TMS TMS (107)
THF, –78 °C
Scheme 38
(105)
i, THF/9 days ii, H2O, –78 °C
TMS
TMS
TMS
+ TMS
TMS
(108), 45%
Me2 Si
TMS
Si Me2 (109), 13%
TMS +
Me2Si TMS (110), 4%
SiMe2
Me2Si
SiMe2
TMS
TMS
+ (111), 1%
Scheme 39
Similarly\ phenyl"tris"TMS#ethylene participates readily in oxidative metallation reaction to give 0\1!dilithiophenyl"tris"TMS##ethane[ Hydrolysis of the dilithio derivative leads to the formation of tris"TMS#phenylethane\ Ph"TMS#CHCH"TMS#1\ in almost quantitative yield ð81CL756Ł[ "d# Transmetallation and related reactions[ There are several useful syntheses using trans! metallation reactions for the preparation of silylmethyl derivatives of alkali and alkaline earth metals[ Bis"bis"TMS#methyl#mercury\ which can be prepared from the Grignard reagent and mercury"II# chloride\ exchanges mercury with lithium and the heavier alkali metals "Equation "15## ð79POL1912Ł[ This procedure has been shown to be a particularly clean method for the generation of a!silyl carbanions[ However\ the dangers inherent in handling volatile mercury compounds make this route somewhat less than attractive[ Bis"TMS#methylpotassium can also be prepared by transmetallation of bis"TMS#methyllithium with potassium t!butoxide in hexane "71)# "Equation "16## ð80OM0693Ł[
083
At Least One Metalloid or Metal TMS
TMS Hg
TMS
M (M = Li, Na, or K) ether, 20 °C
M 2
(26) TMS
TMS
TMS
Li
K
ButOK
(27) TMS
TMS
hexane, 20 °C, 16 h
TMS
TMS
Also included in this category are desilylation of tris"TMS#methane with sodium methoxide in HMPA "Equation "17## ð62TL3082Ł[ The driving force for this reaction may be the formation of a strong Si0O bond of methoxytrimethylsilane[ Similar reactions occur with tetrakis"TMS#methane and bis"TMS#methane ð62TL3082Ł[ TMS TMS
TMS
Na
NaOMe HMPA, 20 °C
(28) TMS
TMS
Dibromo"TMS#methane has been shown to react with a zincÐcopper couple in THF to give the dizinc derivative "TMS#CH"ZnBr#1[ Transmetallation of the compound with magnesium metal a}ords the Grignard reagent "TMS#CH"MgBr#1 ð61JOM"39#C42Ł[
"ii# Bis"TMS#methyl derivatives of transition metals and `roup 02 and 03 metals Practically all compounds of the type RC"SiX2#1"MLm# containing a metal of which the elec! tronegativity is greater than those of lithium and magnesium\ have been prepared by transmetallation reactions starting from a!silyl!substituted organolithiums or Grignard reagents and inorganic or organometallic halides[ A listing of many of these reactions is given in Table 2[ Some speci_c examples are discussed below[ Lithium bis"TMS#methanide reacts with lanthanum aryloxides "Ln La or Sm# under ambient conditions to yield Ln"CH"TMS#1#2*the _rst structurally characterized neutral homoleptic alkyl of the lanthanide metals ð77CC0996Ł[ The conversion of several bis"polymethylcyclopentadienyl#!stabilized lanthanide complexes into bis"TMS#methyl derivatives "001# has been achieved by a low!temperature reaction with bis"TMS#methyllithium[ E}orts to abstract a proton from the a!carbon atom of the lanthanide complex "001^ M Lu# did not yield an alkylidene[ Rather\ a salt "002# was isolated which was assigned a metallacyclobutane structure "Scheme 39# ð74JA7092Ł[ The bis"TMS#methylyttrium complex "003#\ which can be prepared from Cp 1YCl and "TMS#1CHLi\ readily undergoes insertion reactions into the s!yttriumÐcarbon bond to produce new monomeric complexes\ such as "004# and "005#\ stabilized by Cp ligands and "TMS#1CH group "Scheme 30# ð76OM0498Ł[ Compounds "006# have been prepared from the appropriate metallocene dichlorides and an equimolar amount of "TMS#1CHLi in ether[ Sodium amalgam in THF under dinitrogen smoothly reduces the bis"TMS#methylzirconium"IV# metallocenes "006# to complexes of structure "007#\ containing {{side!on|| bonded dinitrogen according to Scheme 31 ð68JOM"070#14Ł[ These results provide a further demonstration that the bulky bis"TMS#methyl ligand may stabilize unusual metal complexes[ The preparation of bis"bis"TMS#methyl#manganese "008# was accomplished by treating anhy! drous manganese"II# chloride with the Grignard reagent in THF as indicated in Scheme 32[ This compound has proved to be a useful agent for transferring the ligand "TMS#1CH from Mn to another metal site[ Thus\ the yield of Pb"CH"TMS#1#1 obtained from structure "008# and PbX1 "X Cl or N"TMS#1# is certainly superior to that achieved in the direct reaction between "TMS#1CHLi and PbX1 ð89JOM"283#46Ł[ Mononuclear cuprate "019# was prepared as its lithium crown ether salt by addition of the organolithium reagent to CuBr in THF[ Its structure consists of a well!separated cation\ "Li"01! crown!3#1#¦\ and a cuprate anion "Equation "18## ð74JA3226Ł[
At Least One Metalloid
084
Table 2 Preparation of bis"TMS#methyl derivatives of transition metals and group 02 and 03 metals[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Silyl rea`ent Yield Metal substratea ðR "TMS#1CHŁ Product ")# Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * ScCl2 RLi ScR2=1THF 63JOM"65#C34 RLi YR2 63JOM"65#C34 YCl2 RLi YCp1 R 58 75OM0615 YCp1 Cl YCp1 "OAr#1 RK YCp1 "OAr#R 61 83OM58 RLi LaR2 77CC0996 La"OAr#2 ðLaCp1 Cl1Ł−Li¦ RLi LaCp1 R 59 74JA7980 RLi CeCp R1 77CC851 CeCp "OAr#1 ðNdCp1 Cl1Ł−Li¦ RLi NdCp1 R 79 74JA7980 RLi SmR2 77CC0996 Sm"OAr#2 ðSmCp1 Cl1Ł−Li¦ RLi SmCp1 R 34 74JA7980 ECl2 RLi ðER2ClŁðLi"THF#3Ł 67CC039 RLi ðYbR2ClŁðLi"THF#3Ł 67CC039 YbCl2 RK LuR2"m!Cl#K"OEt#1 80OM0693 LuCl2 ðLuCp1 Cl1Ł−Li¦ RLi LuCp1 R 53 74JA7980 RLi TiR2 5 67JCS"D#623 TiCl2"Me2N#1 TiCp1Cl1 RLi TiCp1R 52 66JA5534\ 67JCS"D#623 RLi ZrClR2 34 67JCS"D#623 ZrCl3 ZrCp1Cl1 RLi ZrCp1ClR 32 66JA5534 RLi ZrCp1?ClR 32Ð68 68JOM"070#14\ 70JCS"D#703 ZrCp1?Cl1 HfCl3 RLi HfClR2 42 67JCS"D#623 HfCp1Cl1 RLi HfCp1R 26 66JA5534 RLi VR2 03 67JCS"D#623 VCl2"Me2N#1 RLi VCp1R 31 66JA5534 VCp1Cl1 VCp1Br RLi VCp1R 79 66JA5534 CrCl2 RLi CrR2 60 67JCS"D#623 RMgCl MnR1=THF 61 89JOM"283#46 MnCl1 CuBr RLi ðCuBrRŁLi 74JA3226 ZnCl1 RLi ZnR1 67 80JOM"310#064 RLi:TMEDA ðZnR2ŁLi 62 82ZAAC"508#564 ZnCl1 CdCl1 RLi CdR1 23 67JOM"042#142 HgCl1 RLi HgR1 86 67JOM"042#142 "TMS#1CMeLi HgðC"Me#"TMS#1Ł1 23 67JOM"042#142 HgCl1 RMgCl HgR1 66 55JOM"5#340 HgCl1 HgCl1 R1Hg HgClR 61 55JOM"5#340 RLi HgR1 05 69JOM"13#536 HgBr1 HgBr1 R1Hg HgBrR 25 67JOM"042#142 RLi AlClR1 36 67JOM"042#142 AlCl2 AlCl2 RLi AlR2 58 78ZAAC"468#64 RLi AlBut1R 59 81ZAAC"502#56 "AlBrBut1#1 "AlBr1But#1 RLi AlButR1 67 80ZAAC"484#114 "AlCl1#1CH1 RLi "AlR1#1CH1 34 89POL166 RLi GaR2 71 79IC2526 GaCl2 RLi GaR2 31 78JOM"253#178 Ga1Br3 Ga1Br3"diox#1 RLi GaR1Br 43 81CB0436 RLi ðGaR1Ł1 52 78JOM"253#178 Ga1Br3"diox#1 InCl2 RLi InR2 89 79IC2526 InPriCl1 RLi InCl"R#Pri1 50 80ZN"B#0428 RLi ðInR1Ł1 43 78JOM"257#028 In1Br3"TMEDA#1 RLi SnR1 60 75JCS"D#0440\ 65JCS"D#1157 SnCl1 "SnClðN"TMS#1Ł#n RLi SnR1 60 65JCS"D#1157 SnðN"TMS#1Ł1 RLi SnR1 08 65JCS"D#1157 RLi SnCl1R1 73 75JCS"D#0440\ 71CC0396 SnCl3 RLi PbR1 2 65JCS"D#1157 PbCl1 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a
Abbreviations] Ar 1\5!But1C5H2\ Cp h!C4H4\ Cp h!C4Me4\ Cp? h!C4H3X "X H\ Me\ Et\ Pri\ But\ or TMS#[
Studies in the 0879s and early 0889s on the transmetallation reactions of nitrogen!functionalized lithium bis"TMS#methanide "82# have yielded a series of molecules with unusual bonding con! _gurations[ For example\ the reaction of 1!bis"TMS#methylpyridine with butyllithium in THF followed by CuCl\ yields a binuclear complex "010# in which the metal is not involved in electron! de_cient bonding ð72CC0308Ł[ The silver"I# bis"TMS#methyl derivative "011# was prepared by a similar method "Scheme 33# ð73CC501Ł[ The thermally stable N!functionalized bis"TMS# methylcobalt"II# complex has been prepared by reacting the lithium derivative "82# with cobalt"II# chloride in ether ð82JOM"332#C28Ł[ An x!ray structural study has revealed a centrosymmetric molec! ular skeleton in which a pair of pyridine ligands are trans!chelated to the central planar four!
085
At Least One Metalloid or Metal (TMS)2CHLi
[Me2SiCp*2MCl2]–Li(THF)+2
TMS
ButLi/TMEDA
TMS
hexane (M = Lu)
Me2SiCp*2M (112) –
TMS Me Me2SiCp*2Lu
Si
Li(TMEDA)+3
Me (113) M = Nd, Sm, or Lu Scheme 40
TMS
O
TMS
O
YCp*2
CO2
YCp*2
benzene, 20 °C 27%
TMS
(116)
2ButCN toluene, 20 °C 76%
TMS
TMS
N Y(NCBut)Cp*2
TMS
But
(114)
(115)
Scheme 41
(Zr(η-C5H4R)2Cl2)
TMS
(TMS)2CHLi
Zr(η-C5H4R)2Cl
ether, 20 °C
TMS
Na/ –Hg/N2
TMS
THF, 20 °C
TMS
Zr(η-C5H4R)2(N2)
(117) R = H, Me Scheme 42
[Mg(TMS)(µ-Cl)(THF)]2
MnCl2
(118)
Mn[CH(TMS)2]2(THF)
THF, 20 °C, 18 h 72% Sn[N(TMS)2]2
(119) 1/2 Sn2[CH(TMS)2]4
pentane, –10 °C 71%
(119) PbCl2 hexane, 20 °C 64%
Pb[CH(TMS)2]2
Scheme 43 –
CuBr
CuBr
(TMS)2CHLi/12-crown-4 THF/toluene/hexane
Li(12-crown-4)2+ TMS
(29)
TMS
(120)
coordinate cobalt"II# atom[ The complexes "M"NC4H3C"TMS#1!1#1#\ where M Zn\ Cd\ or Hg\ accessible from structure "82# and MCl1\ are mononuclear metal"II# alkyls in which the dative metalÐ nitrogen interactions progressively weaken in the sequence Zn×Cd×Hg ð75CC561\ 82JCS"D#1542Ł[ Monomeric 1!pyridylbis"TMS#methyltin"II# compounds of structures "012#Ð"014# were prepared from "82# and SnCl1 or Sn"N"TMS#1#1 "Scheme 34# ð77CC225Ł[ Bis"1!pyridylbis"TMS#methyl#stannylene "013# upon treatment with aryl azides forms the 0! aza!7!stannabicycloð2[1[9Łocta!1\3\5!triene system "015# via stannaimine intermediate "Scheme 35# ð82CB1136Ł[ The pentacoordinate aluminum derivative "016# is reported to be formed by reaction of lithium bis"TMS#methanide with AlCl2[ Compound "016# rapidly underwent metalÐhalogen cleavage with AlCl2 in benzene yielding the salt!like adduct "017# "Scheme 36# ð76AG"E#570Ł[
086
At Least One Metalloid TMS N
TMS
TMS
Li
N
i, ii
Li
TMS
M THF, 20 °C
N
TMS
TMS
TMS M N
TMS (93)
(121) M = Cu (122) M = Ag i, BuLi, ether, 1 h at 20 °C; ii, CuCl, THF, 1 h, 20 °C or AgBF4, THF, –78 °C Scheme 44
TMS (TMS)2N
TMS
N
Sn
N Sn
TMS
N
TMS
TMS
TMS (124)
(123) 2Sn[N(TMS)2]2 ether
SnCl2, THF or ether
ClSn (93)
N
TMS
2SnCl2 ether
TMS (125)
Scheme 45
TMS TMS (124)
RN3 hexane, RT
TMS
Sn
Nr
TMS
~TMS
N Sn
N
N
TMS R (126)
2
R = 2,6 Pri2C6H3, 68%, 2,4,6-Me3C6H2, 79% Scheme 46
+
TMS
N Li
TMS
AlCl3 ether, 20 °C 54%
N
TMS Cl
TMS
Al N TMS
TMS
benzene, 20 °C 83%
TMS
N
AlCl3
TMS
Al
TMS N
AlCl4–
TMS
(127) (128) Scheme 47
E}orts to generate a carbanionic species by the reaction of Al"CH"TMS#1#2 with t!butyllithium in the presence of TMEDA have led to 0!sila!2!alanatetane "018#[ The reaction probably involves an attack of the strong base to the bis"TMS#methyl substituent followed by intramolecular addition of a carbanionic center to the coordinatively unsaturated aluminum atom "Equation "29## ð78ZAAC"468#64\ 82CB1526Ł[ In contrast to Al"CH"TMS#1#2\ a sterically less crowded compound "029# reacts with t!butyllithium in the presence of N\N?!dimethylpiperazine "DMP# to give lithium "m! hydrido#trialkylalanate "020# "Equation "20## ð80ZAAC"484#114Ł[
087
At Least One Metalloid or Metal –
TMS
TMS
TMS TMS
ButLi/TMEDA
TMS
Me
TMS
Al
Al pentane, –55 °C 60%
TMS TMS
Li(TMEDA)+
Si
(30)
Me
TMS TMS TMS (129) Me
TMS But
TMS
ButLi/DMP
N
TMS
pentane, –60 °C 71%
N
Al
TMS
TMS
H Al But Me
TMS (130)
(31)
TMS
TMS (131)
A rare example of the double transmetallation reaction is shown in Equation "21#[ Bis"bro! momagnesio#TMS!methane reacts with chlorotrimethylstannane in THF to form bis"tri! methylstannyl#TMS!methane "021# in almost quantitative yield ð75TL5012Ł[ MgBr TMS
SnMe3
2Me3SnCl THF, 20 °C 94%
MgBr
TMS
(32)
SnMe3 (132)
5[95[1[1[1 Functions bearing boron"s# and metal"s# The chemistry and preparation of lithium poly"boryl#methides derived from methanetriboronic esters were reviewed in 0864 ð64S036Ł[ Since the late 0879s\ reviews containing information on the preparation of boron!stabilized carbanions "borylmethide salts# have also appeared ðB!76MI 595!91\ B!77MI 595!90\ 80COS"0#376Ł[ The present section considers the preparation of polyheteroatom species of the general formula RC"BX1#n"MLm#2−n\ where n 0 or 1\ M is metal\ and R H\ alkyl\ or aryl[ No methods exist which can be used to prepare all these types of compounds but there are synthetic routes which have some generality[
"i# Synthesis via metalÐhydro`en exchan`e Alkyllithium reagents and other strong bases can abstract a proton from carbon adjacent to a boryl group generating the metallated borylmethane[ In principle\ the reaction could provide a general method of synthesis\ but in certain cases highly nucleophilic bases react predominantly at the boron atom leading to formation of {{ate|| complexes "Scheme 37# ð54TL2318\ 55TL3204\ 62S26Ł[ Successful metalÐhydrogen exchange may be achieved in several ways as follows] "a# the reagent can be a hindered\ nonnucleophilic base^ "b# the groups around boron can be highly branched so that attack on boron is inhibited on steric grounds^ or "c# the electrophilicity of the boron atom may be lowered by the use of heteroatom substituents ð80COS"0#376Ł[ R1
R2M
M
Y
–R2H
BX2
R1 Y
BX2 R1
R 2M
M+ Y
Scheme 48
–
B(R2)X2
088
At Least One Metalloid
The example provided in Scheme 38 illustrates the generation of potassium bis"boryl#methanide "023# from sterically overcrowded bis"dimesitylboryl#methane ð71JCR"S#021Ł[ Interestingly\ while the reaction of structure "022# with lithium dicyclohexylamide gives lithium dimesitylborylmethide\ Mes1BCH1Li\ in preparatively useful yield\ n!butyllithium attacks at boron to give the borate and t!butyllithium gives the hydroborate by b!hydrogen transfer ð72TL512Ł[ i, (c-C6H11)2NLi ii, Mes2BF
Mes2BMe
Mes2B
THF, 20 °C
BMes2
KH
K
THF
Mes2B BMes2 (134)
(133) Scheme 49
The deprotonation of bis"dialkoxyboryl#methanes has been accomplished with lithium 1\1\5\5! tetramethylpiperidine "LITMP# in the presence of TMEDA in THF "Equation "22## ð71OM19Ł[ However\ the reaction is not completely general[ Thus\ the compound "025# undergoes cleavage instead of deprotonation to give lithiated monoborylmethane "026# "Equation "23## ð71OM19Ł[ Li B O O X
O B X O
LITMP/TMEDA
B O O X
O B X O
THF, –78 °C
(33)
(135) O
O
O =
X
B O
O
O
O
B
B
, O
O
,
O
B
B ,
B O
,
Ph O
O
Ph
B
B
O
O
LITMP/TMEDA
O
Li
THF, –78 °C
B
O
(34)
O
(136)
(137)
Diborylmethide salts can be alkylated by alkyl halides to form 0\0!bis"dialkoxyboryl#alkanes\ which in turn can be deprotonated and alkylated with a second alkyl halide to form `em!diboronic esters\ R0R1C"B"OAlk1##1 ð71OM19Ł[ "ii# Synthesis via transmetallation reactions A transmetallation reaction\ for the purposes of this section\ can be de_ned as a reaction in which a borylalkyl group is transferred from boron to a metal atom by the reaction of an organometallic compound with a suitable polyborylated methane[ The method is widely used for the preparation of lithium tris! and bis"boryl#methides starting from the corresponding polyborylated methanes and organolithium reagents "Equations "24# and "25## ð62JA4985\ 63JOM"58#34\ 64JA4597\ 65JOM"009#14\ 65JOM"003#0Ł[ In a typical procedure\ the tris"dialkoxyboryl#methane and methyllithium are stirred at −67>C in a polar solvent "normally THF or a mixture of THF and dichloromethane#[ The reaction time appears to be substrate!dependent\ but the reaction is generally complete after about 1[4 h at −67>C[ A borylmethide salt can be isolated or used in situ for subsequent derivatization[ It should be noted that compounds such as "024# and "027# are very interesting as reagents for conversion of a carbonyl compound to the homologous aldehyde ðB!66MI 595!91\ 67JOC849\ 79JOC0980Ł[ X O
O
Li MeLi
B
THF, –70 °C
B O O X
O B X O
O
O X
B O
=
B
O
O ,
O
O B B O X O O X (135)
, B
B O
O
(35)
199
At Least One Metalloid or Metal O O O B O B
O
B O B O
O B O B
BunLi THF
O O
Li (36)
B O
O O (138)
The reaction of lithium bis"dialkoxyboryl#methides with organoelement halides\ such as Ph2MCl "M Ge\ Sn\ or Pb#\ provides a general route to bis"boryl#"germyl#methanes and their tin and lead analogues "Equation "26## ð65JOM"009#14Ł[ A further extension of this type of chemistry was the successful conversion of the tin compound "028# to the methide salt "039# stabilized by one boron and one tin atom\ and _nally to bis"triphenylstannyl#ethylenedioxyborylmethane "030# "Scheme 49# ð65JOM"009#14Ł[ Tris"dialkoxyboryl#methide salts react with Ph2MCl in a similar fashion to form compound Ph2MC"B"OAlk#1#2 ð58JA5430\ 62JOM"46#114\ 62JOM"46#120\ 63JOM"58#52Ł[ Li
MPh3 Ph3MCl
B O O X
O B X O
X O
SnPh3 O
B
B
=
or B
B
O M = Ge, Sn, or Pb
O
SnPh3
MeLi
O
O
O
O B
O
THF, –78 °C
B
SnPh3
Ph3SnCl
Li
O
B
47%
O (140) Scheme 50
O O (139)
(37)
B O O X
O B X O
THF/ether 36–77%
SnPh3
O (141)
Treatment of tetrakis"dimethoxyboryl#methane with butyllithium or\ preferably\ lithium methox! ide\ followed by triphenyltin chloride yields tris"boryl#stannylmethane "031#\ which on further treatment with butyllithium disproportionates to form bis"boryl#bis"stannyl#methane "032# "Scheme 40#[ Reaction of the monotin compound "031# with ethylene glycol resulted in the loss of one of the three boron atoms to give "triphenylstannyl#bis"ethylenedioxyboryl#methane "028# "Equation "27##[ The tin compound "032# undergoes similar reaction on treatment with lithium methoxide in meth! anol\ providing an alternative route to "boryl#bis"stannyl#!substituted methanes "Equation "28## ð62JOM"46#114Ł[ (MeO)2B
B(OMe)2
(MeO)2B
B(OMe)2
MeOLi or BunLi
(MeO)2B
Li
THF, 20 °C
(MeO)2B
B(OMe)2
(MeO)2B
SnPh3
(MeO)2B
B(OMe)2
(142)
BunLi
Ph3SnCl
Ph3Sn
1/2
SnPh3
(MeO)2B
THF, –78 °C 93%
65%
B(OMe)2
(143) Scheme 51
SnPh3
HO(CH2)2OH
(142)
acetone, 20 °C 90%
O
B
B
O O (139)
O
(38)
190
At Least One Metalloid SnPh3
MeOLi
(143)
(39) Ph3Sn
MeOH, reflux 57%
B(OMe)2
The reaction of benzylbis"boryl#methane "033# with mercuric dichloride and lithium methoxide in anhydrous methanol resulted in the selective replacement of one boron atom by mercury to form the a!metallated borylmethane "034# "Equation "39## ð65JOM"003#0Ł[ Interaction of boryl"stannyl#! alkanes with alkyllithiums generally leads to cleavage of the tin moiety "Equation "30## ð74OM0589Ł[ A useful reaction of dimesitylboryl"TMS#alkanes is that they readily undergo silicon:lithium ex! change with LiF to form lithium borylmethides ð80COS"0#376Ł[ CH2Ph
CH2Ph O
B
B
HgCl2/NaOMe
O
O O (144)
Me3Sn
B
ClHg
MeOH, 25 °C 77%
O
O
(40)
O (145)
MeLi
O
B
Li
O
B
(41)
O
THF, –100 °C
"iii# Synthesis via addition to vinylboranes and methyleneboranes The very low yields of lithium borylmethide salts "ca[ 4)# obtained from the reactions of alkenyldimesitylboranes with organometallic compounds demonstrates that this is not a very useful method for the synthesis of simple a!metallated borylmethanes[ However\ this approach has proved successful for the preparation of a!metallated silyl"boryl#methanes from 0!TMS!0!dimesityl! borylethylenes "see Section 5[95[1[1[3# and several alkali metal polyborylmethides from methylene! boranes ð80COS"0#376Ł[ A speci_c reaction useful for the synthesis of diboriranide "035#\ is shown in Scheme 41[ Treatment of "035# with the very weak acid t!butyl"TMS#amine leads to formation of "036# ð74AG"E#677Ł[ R1
R2 B Cl
R1
B Cl
K/Na
R1
R2 B
R2
THF, 82%
K
R2
R1R2NH
B R2
R1
R2 B
>90%
R2
K (146)
B R2
K (147)
R1 = TMS, R2 = But Scheme 52
C!Borylborataalkyne "037# with t!butyllithium yields 0\2!diborataallene "038#\ which contains a second t!butyl group in place of the "TMS#1CH group[ Upon treatment with one equiv[ of cyclopentadiene\ the 0\2!diborataallene is transformed into the lithium bis"boryl#methide "049# "Scheme 42# ð77AG"E#0269Ł[ Several cyclic compounds\ such as "040# and "041#\ incorporating a C"Li#B1 unit\ have been made by a related 0\1!addition of the C0Li bond to the B1C multiple bond "Equations "31# and "32## ð89AG"E#0929\ 81AG"E#0127Ł[ Readers are referred to a review by Berndt ð82AG"E#874Ł for more detailed information concerning the synthetic potential of meth! yleneboranes in carbometallation reactions[ Mes Mes
B
•
–
ButLi
B TMS
TMS (148)
–
B 50%
Li
Mes
Mes •
–
B But
But (149) Scheme 53
CpH
2Li+
But
B
B
But
Mes Mes (150)
191
At Least One Metalloid or Metal
B
Ar
Ar
Ph
TMS
B
TMS
PhLi
Li
TMS
B
TMS
(42)
B
Ar
Ar (151) Ar = 2,3,5,6-Me4C6H (Dur)
Ar B Ar
Ar
Ar
B
B
TMS
Li
B
TMS
ButLi
TMS
(43)
But
B B
20%
TMS
Ar
Ar (152) Ar = Dur, Mes
A unique reaction leading to the formation of a C"Sn#B1 function has been described by Berndt and co!workers ð76AG"E#435Ł[ The boranediylborirane "042# which\ according to calculations\ has the nonclassical structure shown in Scheme 43\ behaves toward suitable reagents as if it were the carbene[ Reaction of "042# with a stannylene in pentane led to formation of the stannaethene "043# in quantitative yield[ Compound "043# reacts with HCl to give the 0\2!diboretane "044#[ R
R B
B
TMS
B
Sn[CH(TMS)2]2
:
TMS
TMS B R
TMS
pentane, 20 °C
R (153) R
TMS
B
TMS
B
R CH(TMS)2 Sn CH(TMS)2
HCl
TMS
B
~100%
TMS
B
R
TMS Sn Cl TMS
R (154)
(155) R = But Scheme 54
5[95[1[1[2 Functions bearing germanium"s# and metal"s# Isolable examples of compounds of the type RC"GeX2#n"MLm#2−n "n 0 or 1# are virtually unknown[ The signi_cant contribution to this class of compounds was made by Barton and Hockman who reported the preparation and synthetic utilization of lithium bis"tri! methylgermyl#methide "045# ð79JA0473Ł[ This reagent is formed in good yield by methods similar to those described for the analogous silicon compound "Scheme 44#[ The synthetic utility of "045# has been demonstrated by the reaction with tosyl azide leading to the formation of bis"trimethylgermyl#diazomethane[ The triphenylgermyl group seems to have no acidifying e}ect^ lithiation of "Ph2Ge#1CH1 was i, ii
Me3Ge
Cl
Me3Ge iii
iv
Cl Me3Ge
GeMe3
Li
v
GeMe3
Me3Ge
GeMe3 (156)
i, Li, ether, –23 °C; ii, Me3GeCl; iii, ButLi, THF/HMPA, –78 °C; iv, BusLi, THF, –78 °C; v, Li, ether Scheme 55
192
At Least One Metalloid
neither possible with lithium dicyclohexylamide nor with n!butyllithium or t!butyllithium in the presence of HMPA ð79TCC"81#098Ł[ Treatment of "Ph2Pb#1CHLi with Ph2GeCl produced the germylbis"stannyl#methane "046#\ which was converted into functionalized lithium methide "047# by a transmetallation reaction with phe! nyllithium "Equations "33# and "34## ð79TL1796Ł[ GePh3
(Ph3Pb)2CHLi
Ph3GeBr
(44)
THF, 87%
GePh3 Ph3Pb
Ph3Pb PbPh3 (157)
GePh3
PhLi
PbPh3
(45) Ph3Pb Li (158)
>78%
5[95[1[1[3 Functions with mixed metalloid"s# and metal"s# Only a few totally mixed RC"E0Xn#"E1Ym#MLk molecules "E0 and E1 Si\ Ge\ or B^ M metal# have been described[ If unsymmetrical compounds such as XnE0CH1E1Ym or XnE0CH"Hal#E1Ym are available\ then metalÐhydrogen or metalÐhalogen exchange reactions seem to be the most practical routes to metallated derivatives[ Redistribution represents a potential problem and can be avoided by mild reaction conditions and rapid experimental work up procedures[ Several metallating reagents have been examined\ but the most satisfactory method for metallation of TMS"ethylenedioxyboryl#methane "048# involves the use of LITMP:TMEDA in THF "Scheme 45# ð79CC28\ 72OM129Ł[ In contrast to "048#\ substituted TMS"ethylenedioxyboryl#methanes\ TMSCH"R#BO1C1Me3 "R alkyl\ aryl# have proved resistant to the usual deprotonation conditions ð79JOM"073#C30Ł[ Li TMS
B
O
LITMP/TMEDA
TMS
THF, 0 °C
O
R B O
O
RHa1
TMS
53–85%
B
O
O
(159) R = Bu, Am, Hex, PhCH2, PhCH2CH2, PhOCH2CH2 Scheme 56
Lithiation of TMS"trimethylgermyl#methane may be accomplished with t!butyllithium in a mix! ture THF:HMPA at −67>C[ A successful alternative method utilizes the chloro derivative "Scheme 46# ð79JA0473Ł[ ButLi
TMS
GeMe3
THF/HMPA, –78 °C
Li TMS Cl TMS
GeMe3
Li
GeMe3
ether, reflux
Scheme 57
A versatile approach to metallated polyheteroatom!substituted methanes based on the reactions of tris"triphenylplumbyl#methane has been developed by Kau}mann and co!workers ð79TCC098\ 79TL1796Ł[ Germyl"plumbyl#methide "047# undergoes coupling reactions with TMS!Cl to yield the functionalized methane "059# "Equation "35##[ Transmetallation of silylbis"plumbyl#methanes "051# with PhLi gives a new organolithium reagent as shown in Scheme 47 ð79TL1796Ł[ The required
193
At Least One Metalloid or Metal
lithium bis"plumbyl#methide "050# can be obtained by a transmetallation reaction of "Ph2Pb#2CH with PhLi ð79TL1796Ł[ Li
TMS-Cl
Ph3Pb GePh3 (158)
78%
TMS (46)
Li
TMS-Cl
Ph3Pb PbPh3 (161)
89%
Ph3Pb GePh3 (160) TMS
Ph3Pb
PbPh3
TMS
PhLi >70%
Ph3Pb
Li
(162) Scheme 58
5[95[2 FUNCTIONS CONTAINING THREE METALS 5[95[2[0 Three Similar Metals Isolable compounds of the type RC"MLm#2 "M metal# are known with M Li\ Hg\ Al\ Sn\ and Pb[ Methods of synthesizing polylithiated aliphatic hydrocarbons have been reviewed previously ðB!74MI 595!91\ 76TCC0Ł[ The chemistry and preparation of acyclic compounds with functions containing three heavy main group metals have not been surveyed and only passing comments can be found in appropriate sections of Methoden der Or`anischen Chemie ð69HOU"02:3#0\ 63HOU"02:1b#0\ 67HOU"02:5#070Ł\ Comprehensive Or`anometallic Chemistry ð71COMC!I"6#154Ł and in several spe! cialized books ð53AOC"1#146\ 79TCC"81#098\ B!70MI 595!91\ B!76MI 595!90Ł[
5[95[2[0[0 Lithium derivatives\ RCLi2 Polylithium organic compounds can be prepared by a variety of methods and several have been extensively studied ð76TCC"027#0\ 81MI 595!91Ł[ However\ only a few of these methods are readily applicable to the preparation of geminal trilithioalkanes with at least some degree of generality[ These are] "a# reactions of hydrocarbons or halocarbons with lithium vapor^ "b# transmetallation reactions^ "c# metallation of acidic hydrocarbons^ and "d# pyrolysis reactions[ When applicable\ transmetallation\ especially mercuryÐlithium exchange\ is usually the most convenient and is therefore the method of choice[ On the other hand\ reactions of hydrocarbon or halocarbon substrates with lithium vapor probably represent the most general approach[ CarbonÐ lithium bonds in polylithiated alkanes are very susceptible to hydrolysis and the handling of any such compound requires the use of vacuum systems and other specialized techniques[
"i# Reactions with lithium vapor Direct halogenÐmetal exchange in polyhaloalkanes by treatment with lithium metal\ the most popular method for the synthesis of alkyllithium compounds\ is only of limited value for the preparation of polylithiated alkanes due to a!elimination of lithium halide after the _rst step being faster than the halogenÐmetal exchange ð68AG"E#674\ 79HCA1935Ł[ These di.culties can be overcome by high!temperature reaction of polyhaloalkanes with lithium vapor[ Thus\ tetralithiomethane\ CLi3\ and hexalithiomethane\ C1Li5\ the _rst examples of perlithiated alkanes\ were prepared by the reaction of lithium vapor with the appropriate perchlorocarbons under vacuum at high temperatures "649Ð0999>C# ð61CC0967\ 72JOM"138#0Ł[ The reactions are carried out in a stainless steel reactor consisting of a Knudsen cell containing lithium metal heated in a furnace\ an inlet tube\ and a liquid nitrogen cold _nger[ The main advantage of this technique\ besides the high reactivity of lithium vapor\ is the reduction of rearrangements and secondary
194
Three Metals
reactions from rapid quenching of the products onto the cold _nger ð76TCC0Ł[ In both prep! arations\ depicted in Equations "36# and "37#\ the main by!products were C1Li3 and C1Li1[ Further investigations showed that the selectivity can be improved by working at 649>C instead of 749>C ð64CC291\ 68JOC1200\ 71JA6234Ł[ However\ the method although optimized\ still provides a maximum of 39) CLi3 together with 47) C1Li1 ð72JOM"138#0Ł[ When chloroform was used as a substrate\ trilithiomethane was obtained in 04[4) yield "Equation "38##^ the main side products being 28[6) C1Li1\ 19[0) CLi3\ and 08[0) CH1Li1 ð71JA6234\ 72JOM"138#0Ł[ Similarly\ the reaction of dich! loro"TMS#methane with lithium vapor gave TMS!CHLi1 in only 00) yield "Equation "49## ð73CC0553Ł[ CCl4 + 8Li(g) C2Cl6 + 12Li(g) CHCl3 + 6Li(g) TMS-CHCl2 + 4Li(g)
850 °C
850 °C
750 °C
720 °C
CLi4 + 4LiCl
(47)
C2Li6 + 6LiCl
(48)
CHLi3 + 3LiCl
(49)
TMS-CHLi2 + 2LiCl
(50)
The purest perlithiated ethane "C1Li5# was prepared by using diethylmercury instead of hexa! chloroethane as the starting material ð68JA1103Ł[ It was also reported that the vapor phase reaction of carbon with atomic lithium yielded perlithiopropyne "C2Li3# as the main product ð62JA0232Ł[ The major drawback of a technique utilizing reactions between organic substrates and lithium vapor lies in the separation of a mixture of lithium!substituted hydrocarbons[ Unfortunately\ it has not yet been possible to separate the resulting mixtures\ and even separation from the lithium matrix is di.cult ð72JOM"138#0\ 81AG"E#473Ł[
"ii# Transmetallation reactions In many cases of synthesis of substantial amounts of pure polylithiated alkanes there is no practical alternative to transmetallation reactions ð76TCC"027#0Ł[ However\ since the transmetallation route requires the intermediacy of another organometallic compound\ polylithiated alkanes pre! pared by this method share the same limitations and restrictions that the parent organometallic compound encounters[ In practice\ mercuryÐlithium exchange reactions represent one of the most e}ective routes to the di! and trilithiomethanes because the corresponding organopolymercury compounds are comparatively readily available[ Thus\ trilithiomethane "HCLi2# can be prepared in good yield by treating tris"chloromercurio#methane with lithium metal in dry THF "Equation "40## ð71MI 595!90Ł[ Unfortunately\ direct mercuryÐlithium exchange reaction is not suitable for the synthesis of tetralithiomethane "CLi3#[ Treating C"HgCl#3 with lithium metal in diethyl ether resulted in the dimeric products hexalithioethane "C1Li5# and tetralithioethylene "C1Li3#[ The reaction is believed to proceed via radical intermediates ð76TCC"027#0Ł[ HgCl
Li
Li
(51) ClHg
HgCl
THF, 20 °C
Li
Li
A variant of the mercuryÐlithium exchange method is provided by the reaction of organomercury compounds with n!butyllithium[ Many of the polymercury compounds\ including C"HgCl#3 ð73AG"E#884\ 75OS267Ł and CH1"HgCl#1 ð72AG"E#622Ł\ are useful in this reaction[ However\ the pro! cedure has not yet been adequately developed for synthesis of trilithiated hydrocarbons[ Transmetallation reactions with several other elements\ such as boron and tin\ can also be used for the generation of polylithiated organic compounds ð79TCC"81#098\ 71AG"E#309Ł but trilithiated hydrocarbons have not yet been prepared this way[
"iii# Metallation of acidic hydrocarbons Much more easily accessible than the 0\0\0!trilithiated alkanes are certain perlithioalkynes\ since alkyllithium reagents can abstract quantitatively not only the hydrogen atoms on sp!hybridized
195
At Least One Metalloid or Metal
carbon atom\ but also those of the adjacent methyl group ð63MI 595!90\ 71AG"E#309\ 72T1622Ł[ For example\ the conversion of propyne into perlithiated derivative can be achieved by reaction with n! butyllithium in hexane "Equation "41## ð54JA2677\ 58JA5045\ 73AG"E#884Ł[ BunLi
(52)
C3Li4 hexane, 75%
The pattern of reactivity of conjugated diynes closely resembles that of the propyne[ Thus\ reaction of the 0\2!pentadiyne with excess n!butyllithium:TMEDA in hexane gives the perlithiated hydrocarbon C4Li3 "Equation "42## ð62JA2213Ł[ 1\3!Hexadiyne under the same conditions ð65JA7315Ł or even in the absence of TMEDA ð62JCS"P1#488Ł has been converted into the trilithiated product "Equation "43##[ Metallation of 1\3!octadiyne in diethyl ether or THF a}ords another {{lithiocarbon|| "Equation "44## ð62JCS"P1#488Ł[ BunLi
C5Li4
(53)
MeC5Li3
(54)
hexane BunLi hexane BunLi
C3H7C5Li3
C3H7
(55)
ether or THF
Unlike alkynes\ linear and branched alkenes upon treatment with organolithium reagents form only mono! and dilithiated hydrocarbons[ For example\ propene is dilithiated with n!butyl! lithium:TMEDA in hexane to give the corresponding dianion ð64CC766Ł[ Isobutylene under these conditions yields the cross!conjugated trimethylenemethane dianion ð65T0728Ł[ The isomeric 1! butene can be dilithiated to give 0\3!dilithio!1!butene ð63JA4539Ł[
"iv# Pyrolysis reactions The pioneering work in this _eld is due to Ziegler et al[ who reported that pyrolysis of halide! free methyllithium resulted in the formation of dilithiomethane in excellent yield "Equation "45## ð44ZAAC"171#234Ł[ This procedure is still the method of choice for the preparation of CH1Li1\ however\ it is not the best route to 0\0\0!trilithiated hydrocarbons[ Although perlithiopropyne "C2Li3# was detected among the products of the thermal decomposition of CH1Li1 and CLi3 "Equa! tions "46# and "47##\ it could not be separated from the resulting mixtures ð70JA4840\ 71JA1526\ 74JA4202Ł[ MeLi
CH2Li2
225 °C
350 °C 6 min
225 °C
CLi4 8 min
CLi4 + C3Li4 20% 40%
CH4 + CH2Li2
(56)
C3Li4 + C2Li2 80% 20%
(57)
+ C2Li4 + C2Li2
(58)
30%
10%
5[95[2[0[1 Mercury derivatives\ RC"HgX#2 As in many other cases\ transmetallation represents a valuable route to polymercurated methanes[ Thus\ tris"dimethoxyboryl#methane\ readily available via the reaction of chloroform with di! methoxyboron chloride and lithium metal "see Section 5[95[1[0[1#\ undergoes a rapid reaction with mercuric salts to produce trimercurated methanes "Equation "48## ð79JOM"080#6\ 72JOM"132#134Ł[
196
Three Metals B(OMe)2
HgX
HgX2
(59) (MeO)2B
B(OMe)2
THF, RT
XHg
HgX
X = Cl, 62%; AcO, 38%
However\ despite the usefulness of transmetallation reactions\ this route to trimercurated deriva! tives has rarely been used\ because access is easier via direct mercuration of organic compounds containing an activated methyl group ðB!56MI 595!90\ 57MI 595!90\ 60MI 595!90\ 63HOU"02:1b#0\ B!70MI 595! 91Ł[ Treatment of methyl derivatives containing electron!withdrawing groups with a mercuric salt\ HgX1\ results in electrophilic mercuration giving a mercury derivative[ Use of an excess of HgX1 may give rise to trimercurated compounds[ Typical examples from the literature are given in Table 3[ The reactions are normally carried out in aqueous acidic solutions or without solvent at elevated temperatures[ For example\ acetonitrile reacts with anhydrous mercuric acetate at 049>C for 19 h in a bomb tube to give the trimercurated product in 82) yield "Table 3\ entry 7#[ Conditions for preparing the mono! and dimercurated derivatives of acetonitrile have also been described ð63JPR446Ł[ Table 3 Preparation of 0\0\0!trimercurioalkane derivatives[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Yield Entry Compound Method of preparation ")# Ref[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * HCðB"OMe#1Ł2 ¦HgCl1 51 79JOM"080#6 0 HC"HgCl#2 HCðB"OMe#1Ł2 ¦HgBr1 72JOM"132#134 1 HC"HgBr#2 2 HC"HgI#2 HC"HgOAc#2 ¦KI 71 72JOM"132#134 HCðB"OMe#1Ł2 ¦Hg"OAc#1 27 72JOM"132#134 3 HC"HgOAc#2 4 HC"HgSCN#2 HC"HgOAc#2 ¦KSCN 72JOM"145#106 HC"HgOAc#2 ¦KCN 72 72JOM"132#134 5 HC"HgCN#2 6 HC"HgMe#2 HCðB"OMe#1Ł2 ¦MeHgOAc 75JOM"290#0 MeCN¦Hg"OAc#1 82 63JPR446 7 NCC"HgOAc#2 8 NCC"HgMe#2 MeCN¦"MeHg#1O 84 64ZAAC"304#122 EtOH¦HgCl1:NaOAc 71JOM"127#216 09 OHCC"HgCl#2 00 OHCC"HgBr#2 EtOH¦HgBr1:NaOAc 71JOM"127#216 AcH¦Hg"NO2#1 76JOM"208#0 01 OHCC"HgBr#2 02a HO1CC"HgCl#2 {mercuretin|¦HCl 84 73JOM"165#0 a HO1CC"HgOAc#2 {mercuretin|¦AcOH 43 73JOM"165#0 03 04a HO1CC"HgNO2#2 {mercuretin|¦HNO2 75JOM"295#0 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a
{{Mercuretin||] AcOðHgC"HgOAc#1CO1ŁnH "n½9#[
Mercuration of C0H bonds a to carbonyl groups also occurs readily[ Thus\ reaction of acetic aldehyde with HgCl1 led to the formation of "ClHg#2CCHO in almost quantitative yield[ Mer! curation of the aldehyde RCH1CHO "R Me\ Et# gave "ClCH1#1CRCHO "74Ð77)# ð73CCA578Ł[ The product obtained by boiling an ethanolic solution of mercuric chloride with sodium acetate ð0788CB769Ł has also been identi_ed as tris"chloromercurio#acetaldehyde "Table 3\ entry 09#[ The bromine analogue was obtained in the same way ð71JOM"127#216Ł[ The crystal structures of solvates "ClHg#2CCHO=DMF and "BrHg#2CCHO=DMSO have been determined by x!ray di}raction methods ð71CSC0460\ 71JOM"127#216Ł[ Mercuration of acetaldehyde with mercuric nitrate in aqueous nitric acid always leads to tri! mercurated acetaldehyde\ which separates from the solution in the form of various nitrates whose type and composition depends upon the acid concentration ð76JOM"208#0Ł[ Addition of an ethanolic solution of acetaldehyde to an aqueous solution of mercuric nitrate gives a hydrated oxonium nitrate of tris"mercurio#acetaldehyde\ "OHg2CCHO#NO2=H1O ð72JOM"142#172Ł[ It has been con_rmed that the compounds obtained by melting mercuric acetate\ named mer! curetin ð16JCS1547Ł\ is identical with the compound prepared by heating mercuric acetate in acetic anhydride ð92LA"218#005Ł[ Mercuretin\ prepared by both routes\ has been identi_ed as the con! densation polymer of tris"acetoxymercurio#acetic acid\ AcO"HgC"HgOAc#1CO1#nH\ with n approxi! mately equal to 09[ Its hydrolysis in dilute HCl gives tris"chloromercurio#acetic acid as the only Hg! containing product "Table 3\ entry 02#[ Two nitrates of trimercurated acetic acid\ obtained from the solution of mercuretin in nitric acid were identi_ed as ð"Hg"H1OHg#"NO2Hg#CCO1#NO2Ł and "1"NO2Hg#2CCO1H=HNO2# ð75JOM"295#0\ 80JOM"300#08Ł[ The reaction of 1!ethyl! and 1\3\3\4\4!pentamethyl!0\2!dioxalanium perchlorate with Hg"OAc#1 and Hg"OCOCF2#1 leads to the formation of mono!\ di!\ and trimercurated carboxylic acids depend!
197
At Least One Metalloid or Metal
ing upon the ratio of reagents ð70ZOB1130Ł[ Mercuration of acetone in acidic aqueous solutions produces at least nine mono!\ poly!\ and permercurated species\ all of which can exist in equilibrium simultaneously ð78OM1535Ł[ 5[95[2[0[2 Aluminum derivatives\ RC"AlX1#2 Geminal trialuminioalkanes are available via bishydroalumination of alkynyldialkylalanes ð69HOU"02:3#0Ł[ In general\ the reaction of terminal alkynes with two molar equiv[ of a dialkyl! aluminum hydride in ether or THF lead to 0\0!dialuminioalkanes "Equation "59## ð59LA"518#111\ 55TL5910\ 60CC0482Ł[ However\ in basic solvents such as triethylamine\ the reaction of alkynes with one molar equiv[ of dialkylaluminum hydride produces metallation rather than hydroalumination ð52AG"E#575\ 57IZV809Ł[ This has been used synthetically to prepare alkynylalanes[ Further treatment of the resultant alkynylalanes with excess dialkylaluminum hydride a}ords trialuminioalkanes "052# "Scheme 48# ð59LA"518#111\ 52BSF0351Ł[ R1
2R22AlH
(60)
R1
ether or THF
R22Al
AlR22
R1 2R2
2AlH
R1
AlR22
2R2
AlR22
R1
Et3N, 20 °C
2AlH
70 °C
R22Al
AlR22 (163)
R1 = Bun, R2 = Et Scheme 59
Related preparation of 0\0\0!trialuminioalkanes involves bishydroalumination of alkynylalanes derived from the reaction of alkali metal acetylides with dialkylaluminum chlorides "Scheme 59# ð59LA"518#111\ 57BSF105Ł[ 2R22AlH
R2AlCl
R
Na
80–90%
R
R
AlR2
R2Al
AlR2 AlR2
R = Me, Et Scheme 60
The chemistry of 0\0\0!trialuminioalkanes is not well developed\ and only the reactions of com! pound "052# with electron!donor molecules\ such as LiH\ KF\ Et1O\ and pyridine have been reported ð72IZV525Ł[ 5[95[2[0[3 Tin and lead derivatives\ RC"MX2#2 "M Sn or Pb# Tris"trimethylstannyl#methane "053# can be readily synthesized via interaction of chloroform with trimethylstannyllithium ð64OMS"09#07Ł or via reaction of bromoform with the Grignard reagent obtained from chlorotrimethylstannane and magnesium turning "Scheme 50# ð73JOM"155#26Ł[ Both procedures give the crude product containing substantial quantities of bis"trimethylstannyl#methane[ Distillation and subsequent crystallization from ethanol a}ord a pure substance in average yield[ Cl Me3SnLi
Cl
Cl THF, 20 °C
SnMe3 Me3Sn SnMe3 (164)
Br Br
Me3SnCl/Mg
Br
THF
Scheme 61
198
Three Metals
A more general route to 0\0\0!tristannylalkanes involves the hydrostannation of 0!stannyl!0! alkynes[ Trimethyltin hydride has been shown to react with 0!stannyl!0!alkynes in the presence of catalytic amounts of azobisisobutyronitrile "AIBN# to form predominantly 0\0!distannyl!0!alkenes "054#[ The latter undergo a second hydrostannation to give the corresponding 0\0\0!tristannylalkanes "Scheme 51# ð72JOM"141#36\ 74OM0933Ł[ R
R
Me3SnH
SnMe3
R
SnMe3
SnMe3
+
70 °C, AlBN 8h
Me3Sn
SnMe3 (165) Bun
(166)
But
R(ratio (165)/(166), %): Me (97/3), (96/4), (98/2), Ph (95/5), MeOCH2 (59/41), PhOCH2 (61/39), PhO (165) R = Me,
Me3SnH
R
SnMe3
52–80%
Me3Sn
SnMe3
Bun,
Ph, PhCH2, MeOCH2, PhOCH2, PhO Scheme 62
0\0!Distannyl!1\1!diorganyl!0!alkenes\ resulting from the coupling reaction of geminal dibro! moalkenes with Me2SnLi\ have also been successfully transformed into the corresponding tri! stannylalkanes "Scheme 52# ð75OM0880Ł[ R1
Br
R2
Br
Me3SnLi THF, –78 °C
R1
SnMe3
Me3SnH
R2
SnMe3
hν
R1 R2
SnMe3 SnMe3 SnMe3
R1 = Me, CH2OMe; R2 = Me, Et, Ph, CH2CH2OMe, CH(Me)OMe, CH2CH2OEt, CH2OMe Scheme 63
Oxymetallation of the alkene derivative "056#\ which is achieved by using Me2SnOMe in hexane\ yields functionalized tristannylalkanes "057# "Equation "50## ð80CB492Ł[ The reaction is believed to involve the formation of adduct at the boryl group followed by intramolecular rearrangements[ R2B
SnMe3
R
SnMe3
R Me3SnOMe
MeO B R R
hexane, 25 °C
(167)
SnMe3 SnMe3 SnMe3
(61)
(168) R = Et
The preparative chemistry of triplumbylmethane derivatives is considerably less rich as compared to the chemistry of tristannylmethanes[ The coupling reaction between chloroform and trior! ganylplumbyllithium is the sole valuable route to tris"triorganylplumbyl#methanes ð69JOM"12#360\ 74CB279\ 80SA"A#738Ł[ The method is especially e.cient for triphenylplumbyl derivatives since the Ph2PbLi is readily available from Ph2PbCl and lithium metal "Equation "51## ð74CB279Ł[ Ph3PbCl
Li
Ph3PbLi
PbPh3
HCCl3 THF, –60 °C 91%
(62) Ph3Pb
PbPh3
The following compounds were made analogously^ "Ph2Pb#3C\ "Ph2Pb#1CCl1\ Ph2PbCHCl1\ and "Ph2Pb#1CH1[ Attempts to prepare "Ph2Pb#2CCl and "Ph2Pb#1CHCl failed\ because of further reac! tion with triphenylplumbyllithium ð69JOM"12#360Ł[
5[95[2[1 Three Dissimilar Metals Trimetallated alkanes with di}erent metals attached to carbon are rare[ Even so\ access to these species is of great interest because it is usually di.cult to reach such structures by classical routes[
109
At Least One Metalloid or Metal
A few of the compounds have been prepared by transmetallation or metallation reactions and examples are described in reviews by Kau}mann ð79TCC098\ 71AG"E#309Ł[ The conversion of 0\0\0!tris"diethylaluminio#hexane "052# into lithiobis"diethylaluminio#hexane has been achieved using reactions with n!butyllithium[ It was noted that only one diethylaluminio group can be replaced by lithium even when an excess lithium reagent was used "Scheme 52# ð72IZV525Ł[ H11C5 Et2Al
AlEt2
BunLi
AlEt2
C6H6, 20 °C
H11C5 Et2Al
Li (63) AlEt2
(163)
Compounds with the grouping Sn0C"Li#0Sn are accessible via the reaction of bis"tri! methylstannyl#methane with lithium dicyclohexylamide "LDCA# in presence of 0 mol HMPA ð68TL490Ł[ The nature of the lithium reagent is critical^ generally\ deprotonation occurs with lithium amides\ while transmetallation occurs with alkyllithiums ð79TCC098\ 89S148Ł[ An alternative method for the preparation of lithium bis"stannyl#methide "058# consists of treating a tristannylated com! pound with phenyllithium in ether "Scheme 53#[ Reaction of lithium derivative "058# with Ph2SnCl gave tris"triphenylstannyl#methane ð79TCC"81#098Ł[ LDCA/HMPA
Ph3Sn
SnPh3
THF, 20 °C
Li Ph3Sn SnPh3 Ph3Sn
SnPh3 (169)
PhLi ether, 20 °C
SnPh3
LDCA = lithium dicyclohexylamide Scheme 64
The lithium bis"triphenylplumbyl#methide "069# has been synthesized via several routes^ met! allation of bis"triphenylstannyl#methane\ transmetallation reaction using "Ph2Pb#2CH and phenyl! lithium\ or by halogenÐmetal exchange starting from bromobis"triphenylplumbyl#methane ð79TL1796Ł[ Lithium derivative "069# reacts smoothly with Me2SnCl to give the expected "stan! nyl#bis"plumbyl#methane "060# "Equation "53##[ Li
Me3SnCl
Ph3Pb PbPh3 (170)
THF, 88%
SnMe3 (64) Ph3Pb PbPh3 (171)
The synthetic potential of compounds of structures "058# and "069# in reactions with other metal halides remains unexplored[
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
Comprehensive Organic Functional Group Transformations
6.07 Functions Containing Four Halogens or Three Halogens and One Other Heteroatom Substituent ALEX H. GOULIAEV Aarhus University, A˚rhus, Denmark and ALEXANDER SENNING Technical University of Denmark, Lyngby, Denmark 5[96[0 TETRAHALOMETHANES*C"Hal#3
101
5[96[0[0 Four Similar Halo`ens 5[96[0[0[0 Tetra~uoromethane\ CF3 5[96[0[0[1 Tetrachloromethane\ CCl3 5[96[0[0[2 Tetrabromomethane\ CBr3 5[96[0[0[3 Tetraiodomethane\ CI3 5[96[0[1 Three Similar and One Different Halo`en 5[96[0[1[0 Tri~uoromethyl halides 5[96[0[1[1 Trichloromethyl halides 5[96[0[1[2 Tribromomethyl halides 5[96[0[1[3 Triiodomethyl halides 5[96[0[2 Two Similar Halo`ens 5[96[0[2[0 Di~uoromethylene dihalides 5[96[0[2[1 Dichloromethylene dihalides 5[96[0[2[2 Dibromomethylene dihalides 5[96[0[2[3 Diiodomethylene dihalides 5[96[0[3 Bromochloro~uoroiodomethane\ CBrClFI
101 101 103 104 105 106 106 119 111 112 112 112 113 115 116 117
5[96[1 METHANES BEARING THREE HALOGENS
117
5[96[1[0 Three Halo`ens and a Chalco`en 5[96[1[0[0 Three halo`ens and an oxy`en function 5[96[1[0[1 Three halo`ens and a sulfur function 5[96[1[0[2 Three halo`ens and an Se or Te function 5[96[1[1 Three Halo`ens and a Group 04 Element 5[96[1[1[0 Three halo`ens and a nitro`en function 5[96[1[1[1 Three halo`ens and a phosphorus function 5[96[1[1[2 Three halo`ens and an As\ Sb\ or Bi function 5[96[1[2 Three Halo`ens and a Metalloid 5[96[1[2[0 Three halo`ens and a silicon function
100
117 117 121 126 126 126 131 132 132 132
101
Four Halo`ens or Three Halo`ens and One Other Heteroatom 132 133 133
5[96[1[2[1 Three halo`ens and a boron function 5[96[1[2[2 Three halo`ens and a `ermanium function 5[96[1[3 Three Halo`ens and a Metal Function
5[96[0 TETRAHALOMETHANES*C"Hal#3 The _rst part of this chapter is con_ned to a limited number of compounds\ they are the 24 possible tetrahalomethanes "Table 0# of which many are commercially available plus a few tri~uoromethyl compounds of hypervalent iodine which have been prepared[ Most of the tetra! halomethanes have been prepared with the exception of the eight iodine!containing tetra! halomethanes\ CClI2\ CFI2\ CBrCl1I\ CBr1ClI\ CBr1I1\ CClFI1\ CBrClI1 and the chiral CBrClFI[ Information on high yielding and selective syntheses of CBrI2\ CCl1I1 "formed as a by!product# and CBrFI1 "04) as a by!product# is\ however\ also rather sparse[ Organic per~uoro compounds have many practical applications\ such as in refrigerants\ as propellants\ as _re extinguishers\ in the plastics industry as well as in the manufacture of phar! maceuticals\ whereas perchloro "apart from CCl3#\ perbromo and periodo compounds are more or less only of academic interest[ Methods for introducing ~uorine into organic compounds are presented elsewhere in this volume and are not discussed in this chapter[ For more information there is a number of excellent books on haloorganic compounds[ Organic ~uorine compounds have been treated by several authors[ The most recent handbook is Hudlicky|s Chemistry of Or`anic Fluorine Compounds ðB!81MI 596!90Ł[ This book covers all _elds of organic ~uorine chemistry\ including methods for introducing ~uorine into organic compounds\ reactions\ properties\ analysis and practical applications of these\ as well as synthetic procedures and the synthesis of ~uorinating agents[ Olah et al[ ðB!81MI 596!91Ł have published a book covering the synthesis of ~uorine compounds\ as have Liebman et al[ ðB!77MI 596!90Ł\ whereas German and Zemskov mainly cover reagents for the synthesis of ~uorine compounds ðB!78MI 596!90Ł[ Older books include Chambers| Fluorine in Or`anic Chemistry ðB!62MI 596!90Ł\ Sheppard and Sharts| Or`anic Fluorine Chemistry ðB!58MI 596!90Ł\ and\ _nally\ Emeleus| The Chemistry of Fluorine and Its Compounds ðB!58MI 596!91Ł\ which covers mainly the inorganic chemistry of ~uorides[ Organic bromine compounds have been described by Jolles in Bromine and its Compounds ðB!55MI 596!90Ł[
5[96[0[0 Four Similar Halogens 5[96[0[0[0 Tetra~uoromethane\ CF3 Treatment of metal carbides with ~uorine at 19>C for 89 min or with CoF2 at 339>C for 8 h leads to mixtures of various ~uorocarbons among which CF3 predominates[ Thus\ Cr1C2 yields 80) CF3\ as do Al3C2 "77)#\ B3C "77)#\ TiC "75)#\ Fe2C "75)#\ CaC1 "64)# and WC "56)# ð48JA795Ł[ Fluorination of silicon carbide with F1 also leads to CF3 "Equation "0## ð49IS060Ł[ MnCm + F2
20 °C, 90 min
CF4 + C2F6 + C3F8 + C4F10
relative yields: 68–91%
6–26%
2–14%
(1)
0–2%
M, n, m: see text for specification.
Tetra~uoromethane is furthermore formed\ in better than 49) yield\ upon ~uorination of acti! vated charcoal with F1 ð28JA1851Ł\ or upon ~uorination of graphite with PF2\ AsF2\ SF5\ CuF1\ FeF2\ VF4 at 899Ð0199>C ð44USP1698075\ 44USP1698077\ 44USP1698089Ł\ PF4 at 1339>C ð47GEP0939900Ł or HgF1 at 459Ð799>C ð44USP1698076Ł[ Fluorination "F1# of tri~uoromethane ð26JA0199\ 25CB188Ł or tetrachloromethane at 69>C in the presence of As gives a relative yield of 63) CF3 with CClF2 as the main by!product ð39JA2366Ł[ Treatment of tetrachloromethane ð20USP0850511Ł or tetraiodomethane ð37JCS1077Ł\ under readily available laboratory conditions\ with BrF2 as ~uorinating agent also leads to tetra~uoromethane "Equation "1#\ Table 1#[
102
Tetrahalomethanes
Table 0 Bibliographic information on the preparation\ melting points and boiling points of the tetra! halomethanes[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Formula CA Re`[ no[ Beilsteins Handbuch der Gmelin Handbuch der M[p[ B[p[ Or`anischen Chemiea Anor`anischen Chemieb ">C# ">C# ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * CX3 CF3 64!62!9 H 48\ I 7\ II 00\ III 24\ IV 15 81:82 −073c −029c CCl3 45!12!4 H 53\ I 01\ II 11\ III 53\ IV 45 028:039 −12c 66c CBr3 447!02!3 H 57\ I 06\ II 24\ III 81\ IV 74 143 77Ð89c 089c Cl3 496!14!4 H 63\ I 08\ II 28\ III 093\ IV 87 162:172 057c 029Ð039 "0!1 torr# CF2X CClF2 CBrF2 CF2I
64!61!8 64!52!7 1203!86!7
III 31\ IV 23 III 72\ IV 62 III 87\ IV 81
181:182 295:296 203
−070c −057c
−79c −46 to −47c −11[4c
CCl2X CCl2F CBrCl2 CCl2I
64!58!3 64!51!6 483!11!8
H 53\ III 52\ IV 43 H 56\ II 20\ III 74\ IV 66 H 60\ III 88\ IV 84
212 228 172:181\ 186:187\ 238
−000 to −009c −5c −08a
12[6c 094c 031a
CBr2X CBr2F CBr2Cl CBr2I
242!43!7 483!04!9 03238!79!4
I 06\ III 80\ IV 74 H 57\ II 24\ III 80\ IV 74 H 60\ IV 85
173:181\ 186\ 226:228 172:181\ 186\ 238:240 186:187\ 240
−62[5c 44a 24d"dec[#
095Ð096c 059a
CI2X CFI2 CClI2 CBrI2
0384!38!3 03238!71!6 447!05!6
H 63
186::187 186:187\ 240 186:187\ 240
002a
CF1X1 CBrClF1 CClF1I CBrF1I
242!48!2 319!38!4 642!55!1
IV 64 IV 83
241:243\ 271:274 272\ 274 272\ 274
−048[4b\e
−3f 22f 53[4Ð54[4g "635 mmHg#
CCl1X1 CCl1F1 CBrCl1F CCl1FI CBrCl1I
64!60!7 242!47!1 319!37!3 39798!80!3
H 50\ III 37\ IV 39 IV 65 IV 84
243\ 272\ 274 243\ 272\ 274 272\ 275 272\ 275
−047c −095b −096b
−18[7c 40Ð41f 89b
CBr1X1 CBr1F1 CBr1Cl1 CBr1ClF CBr1FI CBr1ClI
64!50!5 483!07!2 242!44!8 0367!93!1 39798!82!5
I 05\ III 76\ IV 79 H 57\ III 77\ IV 71 III 76\ IV 71
241:243\ 264:267 242:243\ 268:271 243\ 272\ 275 272\ 275 272\ 275
−039h 11a
12[7b\e 024a 68Ð79c
CI1X1 CF1I1 CCl1I1 CBr1I1 CClFI1 CBrFI1 CBrClI1
0073!65!4 483!12!9 03948!89!5 242!38!0 642!56!2 39798!83!6
243\ 267:268 271 271 272\ 275 272\ 275 272\ 275
79[4b\e 74i
CBrClFI CBrClFI "R# CBrClFI "S# CBrClFI "2# CBrClFI " # 642!54!0 275 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a Beilsteins Handbuch der Or`anischen Chemie ðB!07MI 596!90\ B!17MI 596!90\ B!30MI 596!90\ B!48MI 596!90\ B!61MI 596!91Ł[ Gmelin Handbuch der Anor`anischen Chemie ðB!63MI 596!91Ł[ c From Aldrich|s catalog of chemicals ðB!82MI 596!90Ł[ d From Dehn ð98JA0119Ł[ e Calculated value[ f From Haszeldine ð41JCS3148Ł[ g From Burton et al[ ð71JFC"19#78Ł[ h From Miller and Smyth ð46JA19Ł[ i From Holand ð0776LA"139#114Ł[ b
103
Four Halo`ens or Three Halo`ens and One Other Heteroatom
Table 1 Synthesis of ~uorotrihalo!\ di~uorodihalo!\ tri~uorohalo! and tetra~uoromethanes with BrF2 and IF4[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Tetrahalomethane Relative Relative Temp[ Reaction Total Productsa "relative amount 0# amount amount ">C# time yield ")# "ratio# of IF4 of BrF2 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * 9[22 RT 50 CCl1F1 "4# CCl2F "84# CCl3 9[5 9[73Ð0[95c
−67 to RTb RT
78 54Ð69
CCl1F1 "74# CCl2F "04# CCl1F1"04Ð32# CClF2 "46Ð74#
CCl2F
9[7
RT
85
CCl1F1
CBr3
9[22 9[55
−9 9
83 75
CBr2F "½099# CBr1F1 "trace# CBr2F "½11# CBr1F1 "½77# CBrF2 "trace# CBrF2 CBr2F "trace# CBr1F1 "¼099# CBrF2 "trace# CF3 "trace#
0d
9 89
9[52 CI3e
83 72
2h
0[81
RT 37 CBr1F1 "22# CF3 "56# 9[77 RT to 89Ð099 29 min 54 CIF2 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Source] Banks et al[ ð37JCS1077Ł[ a Volatile products were collected in cold traps[ b Tetrachloromethane was added to solid BrF2 in carbon dioxide[ c The reaction was conducted in an autoclave[ d Bromine tri~uoride was added dropwise[ e Tetraiodomethane was added dropwise over 1 h[
CI4 + BrF3 (1:2)
RT
CBr2F2 + CF4 48% (33:67)
(2)
Tetra~uoromethane can furthermore be made by electrochemical means with HF as the ~uorine donor[ Thus\ electrochemical ~uorination of trimethylamine yields mainly tris"tri~uoromethyl#! amine\ but also some tetra~uoromethane "Equation "2## ð41USP1505816Ł\ whereas electro! chemical ~uorination of dimethyl sul_de "Equation "3## yields CF3 as well as sulfur hexa~uoride and tri~uoromethylsulfur penta~uoride ð42JCS1261Ł[ Electrochemical ~uorination of acetic acid\ acetyl chloride\ acetone\ trimethylacetic acid\ acetonitrile or methanol in HF with nickel anodes and iron cathodes as well as acetic acid with a KF¦2 HF melt have also been applied in the synthesis of tetra~uoromethane ð38MI 596!90Ł as has the electrolysis of concentrated tri! ~uoroacetic acid solutions with platinum electrodes "Equation "4## ð22BSB091Ł[ HF, electrolysis
NMe3
N(CF3)3 + CHF3 + CF4 + NF3
(3)
(CF3)2SF4 + CF3SF5 + CF4 + SF6
(4)
HF, electrolysis
SMe2 97%
2% electrolysis
21%
60%
17%
CF4 + C2F6 + CO2 + O2
CF3CO2H
(5)
Other possibilities involve bond breaking in per~uoroalkenes\ for example oxidation of tetra! ~uoroethylene with dioxygen which yields carbon dioxide and tetra~uoromethane "Equation "5## ð33USP1240289Ł[ F
F
F
F
O2
CF4 + CO2
(6)
5[96[0[0[1 Tetrachloromethane\ CCl3 An old review on the preparation of tetrachloromethane exists ðB!37MI 596!90Ł[ A major technical preparation uses chlorination of carbon disul_de at 29>C in the presence of an iron catalyst with formation of tetrachloromethane and disulfur dichloride[ The actual chlorinating agent is S1Cl1 and the sulfur formed is rechlorinated to S1Cl1 "Scheme 0# ð63MI 596!90\ B!82MI 596!92Ł[
104
Tetrahalomethanes
Tetrachloromethane and disulfur dichloride can be separated by careful distillation in an inert gas stream ð64USP2773874Ł[ iron catalyst 30 °C
CS2 + 3Cl2
CCl4 + S2Cl2
CS2 + 2S2Cl2
CCl4 + 6S
2Cl2 + 4S
2S2Cl2
2CS2 + 5Cl2
2CCl4 + S2Cl2
+ 2S
Scheme 1
Tetrachloromethane is also commercially prepared by chlorination of chloromethane\ formed by chlorination of methane or\ more commonly\ by treatment of methanol with hydrogen chloride ð56MI 596!90\ 63MI 596!90\ 70MI 596!90\ B!80MI 596!91\ B!82MI 596!91Ł[ Another industrial procedure for the manufacture of chloromethanes uses a CuCl1:KCl melt as catalyst and chlorine source[ This melt is regenerated by an oxychlorination procedure which uses the HCl produced in the chlorination reaction[ The overall reaction is presented in Equation "6# ðB!82MI 596!91Ł[ CH4
CuCl2/KCl melt
+ HCl + O2
MeCl + higher chloromethanes + H2O
(7)
Other processes involve heating of animal charcoal\ CO\ Cl1 and PCl2 at 399>C at 09 atm in an autoclave with AlCl2 and FeCl2 as catalyst\ which gives an 74) conversion to CCl3 ð56MI 596!90Ł[ Pyrolysis of hexachloroethane at 299Ð319>C yields a mixture of CCl3 and CCl1CCl1 ð49TFS184Ł[ Increasing the temperature to 699Ð799>C causes further degradation of tetrachloroethylene to tetrachloromethane "Scheme 1# ð26GEP57954\ 45BRP638397Ł\ and subjecting propene to chlorinolysis at 349Ð449>C produces a mixture of tetrachloroethylene and CCl3 the ratio of which ranges from 24 ] 54 to 54 ] 24 depending on the exact conditions used "Equation "7## ðB!82MI 596!91Ł[ Cl3C
CCl3
300–420 °C
Cl
Cl
Cl Scheme 2
Cl
CCl4
Cl
Cl2
CCl4 450–500 °C
700–800 °C
+
Cl
+
Cl (35:65 to 65:35)
CCl4
(8) Cl
Thermal decomposition at 599>C of trichloroacetyl chloride gave a low yield "16)# of tetra! chloromethane in admixture with hexachloroethane "Table 2# ð28JA324Ł[ Under severe conditions "499>C\ in the presence of FeCl2# it is also possible to chlorinate benzene and naphthalene to CCl3 in high yields "83)# ð56MI 596!90Ł[ Finally\ yields of 89) or more have been achieved by passing thiophosgene with gaseous MoCl4 or WCl5 at 7 atm over activated charcoal at 329>C ð56MI 596!90Ł[
5[96[0[0[2 Tetrabromomethane\ CBr3 Tetrabromomethane is formed in a relative yield of 83) with an admixture of 5) CClBr2 upon treatment of CCl3 with HBr:AlBr2^ overall yield 76) "Equation "8## ð40USP1442407Ł[ It can be made\ furthermore\ from tribromomethane "or acetone# by oxidation with a sodium hypobromite solution containing excess bromine ð21JA1914Ł[ This reaction is probably catalyzed by antimony"III# chloride ð0769LA"045#59Ł[ CCl4
HBr/AlBr3
CBr4
+ CClBr3
(9)
87% (94:6)
Tetrabromomethane can also be made in a manner similar to the method used in the manu! facturing of CCl3\ but with CS1 and Br1 ðB!82MI 596!91Ł[
105
Four Halo`ens or Three Halo`ens and One Other Heteroatom
Table 2 Synthesis of tetrahalomethanes by thermal decomposition of trihaloacetyl halides or metal halo! acetates in the presence of halogen[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Temp[ Yield Products Ref[ Startin` material X1 ">C# ")# "ratio# ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * 599 29 CCl3"78# CCl2CCl2"00# 28JA324 CCl2COCl CCl2COBr 399 04 CBrCl2"56# CCl2CCl2"22# 28JA324 039 79 CBrCl2"83# CCl2CCl2"5# 28JA324 CCl2COI CF2CO1Na I1a 179 50 CF2Ib 40JCS473 CF2CO1K I1a 179 44 CF2Ib 40JCS473 I1a 179 21 CF2Ib 40JCS473 "CF2CO1#1Bag "CF2CO1#1Hgg I1a 149 24 CF2Ib 40JCS473 I1a 149 15 CF2Ib 40JCS473 "CF2CO1#1Pbg Cl1a RT 89 CClF2b 40JCS473 CF2CO1Ag a b Br1 49 77 CBrF2 40JCS473 78Ð83 CF2Ib 40JCS473 I1a CCl2CO1K Cl1 009Ð019 "trace# CCl3 0766CB567 009Ð019 ×69 CBrCl2 0766CB567 Br1 I1 009Ð019 "trace# CCl2I 0766CB567 ClI 009Ð019 "trace# CCl3 0766CB567 Cl1a 079Ð159 77 CCl1F1b 41JCS3148 CClF1CO1Agc Br1a 079Ð159 80 CBrClF1b 41JCS3148 079Ð159 67 CClF1Ib 41JCS3148 I1a Br1a 079Ð159 70 CBr1F1b 41JCS3148 CBrF1CO1Agd I1a 079Ð159 4 CBrF1Ib 41JCS3148 CCl1FCO1Age Cl1a 079Ð159 52 CCl2Fb 41JCS3148 079Ð159 47 CBrCl1Fb 41JCS3148 Br1a a b 079Ð159 09 CCl1FI 41JCS3148 I1 CBrClFCO1Agf Cl1a 079Ð159 52 CBrCl1Fb 41JCS3148 079Ð159 60 CBr1ClFb 41JCS3148 Br1a ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a Excess X1 "0[4 times the amount of metal haloacetate# was used[ b The products were continously removed by pumping through a cold trap cooled with liquid air[ c Silver chlorodi~uoroacetate was prepared in 54) yield by permanganate oxidation of 0\0\1\2!tetrachloro!2\2! di~uoropropene\ followed by Ag1O:P1O4 treatment[ d Bromodi~uoroacetic acid was prepared "7) yield# by Swarts| method 92MI 596!90 and converted to the silver salt by Ag1O:P1O4 treatment[ e Prepared as a mixture of CCl1FCO1Ag and CHClFCO1Ag "22 ] 56# by treatment of chloro~uoroacetic acid with 19) excess Cl1\ followed by hydrolysis of the intermediate acid chloride[ The silver salts were prepared by treatment of the corresponding acids with Ag1O:P1O4 "46)#[ f Silver bromochloro~uoroacetate was prepared in an overall yield of 12) by treatment of bromo~uoroacetic acid with 19) excess Cl1\ followed by hydrolysis of the intermediate acid chloride[ The silver salt was prepared by treatment of the corresponding acids with Ag1O:P1O4[ g Barium tri~uoroacetate was prepared from tri~uoroacetic acid and Ba"OH#1[ Mercury and lead salts were made similarly from tri~uoroacetic acid and mercury"II# and lead"II# oxide\ respectively[
5[96[0[0[3 Tetraiodomethane\ CI3 Tetraiodomethane may be made in the laboratory by heating CCl3 with CaI1 ¦1 H1O or LiI¦0[4 H1O for 4 days at 89Ð81>C in an evacuated reaction vessel "yield 49Ð44)# ð04CR"045#541\ B!82MI 596! 93Ł\ by treatment of acetone with KI:NaOCl "sat[# ð04CR"045#541Ł or by treating triiodomethane with potassium hypoiodite under exclusion of light at 79Ð89>C ð16BSF0140Ł[ The synthesis of tetraiodomethane from acetone or triiodomethane su}ers from the fact that only small quantities are preparable and that puri_cation is di.cult[ On the other hand\ the synthesis from tetrachloromethane and lower alkyl iodides allows the preparation of larger quantities of tetraiodomethane\ giving nearly quantitative yields and a high! purity product\ for example starting from CCl3 in the presence of AlCl2 and iodoethane "0 ] 9[1 ] 3[9# ð49IS26Ł or iodomethane "0 ] 9[91 ] 3[1# ð34JA0531Ł as the iodine donor[ The chloromethane or chloroethane formed during the reaction is distilled o} from the reaction vessel "Equations "09# and "00##[ + MeI
CCl4
(1:4)
CCl4
+ EtI (1:4)
AlCl3 (cat.) 40 °C, 2 h
AlCl3 (cat.) RT, 45 min
CI4
+ MeCl
(10)
92% (purity 99%)
CI4 + quant.
EtCl
(11)
Crystalline CI3 can be prepared by irradiation of a mixture of CF2I and CO1 at 29 torr[ Carbon dioxide seems\ under these conditions\ important for the formation of CI3 ð75MI 596!90Ł[
106
Tetrahalomethanes
Tetraiodomethane may be puri_ed by recrystallization from chloroform or benzene in vacuo ð34JA0531\ 26JOC65Ł[ When stored\ tetraiodomethane should\ like other iodine containing tetra! halomethanes\ be protected from oxygen\ water and light ð26JOC65Ł[
5[96[0[1 Three Similar and One Different Halogen 5[96[0[1[0 Tri~uoromethyl halides "i# Chlorotri~uoromethane\ CClF2 Chlorotri~uoromethane also known as Freon 02\ is formed in 84) yield upon treatment of tetra~uoromethane with SbF2Cl1 = 1HF at 059>C and 69 atm ð36CI"L#316Ł\ and furthermore as a by! product "06)# in the preparation of CF3 from CCl3 with F1:As\ as mentioned previously ð39JA2366Ł[ Chlorotri~uoromethane has\ however\ been prepared in numerous ways such as by treatment of CCl3 with ~uorine in the presence of iodine or CoF2 ð20ZAAC"190#134Ł\ as well as with HF and di}erent oxometal ~uoride or metal ~uoride catalysts "Equation "01## ð45USP1633036\ 45USP1633037\ 45USP1634775\ 45USP1637066Ł and with antimony"V# chloride as catalyst at 79Ð059>C ð42USP1547816Ł[ Chlorotri~uoromethane is also formed when CCl1F1 is kept in contact with oxoaluminum chloride ð43USP1583628Ł or\ under more severe conditions\ upon treatment of CCl1F1 with F1 in the presence of Hg at 239Ð269>C ð39JA2366Ł[ AlF3
CCl4 + HF (1:1.25)
CCl2F2 + CCl3F + CClF3 90% (35:60:5)
300 °C
(12)
Chlorotri~uoromethane also constitutes the main product of the chlorination of graphite in the presence of HF "Equation "02##[ This reaction has been optimized and found to be most e.cient when conducted at 499>C[ The e}ects of di}erent catalysts have also been investigated ð44USP1698073Ł[ C
Cl2, HF
CCl3F +
CCl2F2 + CClF3
500 °C, 3 h
+ CF4 + haloethanes
(13)
89% (7:21:53:14:5)
By use of BrF2 as ~uorinating agent chlorotri~uoromethane may be prepared in the laboratory ð37JCS1077Ł[ Banks et al[ ð37JCS1077Ł found that slow addition of the ~uorinating agent "BrF2 or IF4#\ lowering of the ratio of tetrahalomethane to ~uorinating agent as well as low temperature and an e.cient condensing system "in order to keep the more volatile intermediates in contact with BrF2 or IF4# favors the formation of tri~uorohalomethanes and tetra~uoromethane[ Bromine tri~uoride reacts smoothly\ but vigorously with CCl3 "Equation "03## and CBr3 whereas the reaction is violent in the case of CI3[ These reactions can be conducted at 9>C[ Iodine penta~uoride\ on the other hand\ is less reactive and the reactions were conducted at 89Ð099>C "vide infra# "Table 1#[ CCl4 + BrF3 (1:0.84–1)
RT
CCl2F2 + CClF3
(14)
65–70% (15–43 to 57–85)
Other possibilities include ~uorination of CHCl2 by the versatile ~uorinating agent CF2OF which yields a mixture of CCl1F1 "5)#\ CClF2 "72)# and CF3 "00)# ð48JA0978Ł[ Carbonyl di~uoride may by PCl4 treatment at 154Ð249>C be converted to a mixture of ~uorochloromethanes "Equation "04## as may phosgene by treatment with HF:Cl1:FeCl2 at 314>C for 06 h "Equation "05## ð46JA4790Ł[ Calcium ~uoride:antimony penta~uoride treatment of phosgene at 499>C for 5 h ð45USP1646103Ł leads to a mixture with CClF2 as the main product "Equation "06##[ COF2 + PCl5
autoclave
(1:1.25)
265 °C, 16 h
(1:2.7)
350 °C, 12 h
CCl2F2 + CClF3 + CCl4 + 15% (67:33:0:–:–) 35% (14:0:86:–:–) X, Y = Cl, F
COXY + CO2
(15)
107
Four Halo`ens or Three Halo`ens and One Other Heteroatom FeCl3/C
COCl2 + HF + Cl2
COCl2
CCl2F2 + CClF3 + CF4
425 °C, 17 h autoclave
(6:6:1) CaF2/SbCl5
CClF3 +
CCl2F2 + CClF3 + CF4 + CCl4
500 °C, 6 h
(16)
72% (19:75:6)
(17)
(65:30:5:trace:trace)
Silver tri~uoroacetate when treated with chlorine also forms chlorotri~uoromethane ð40JCS473Ł\ as does photochlorination of tri~uoromethane ð26JA0199Ł and cleavage of hexa~uoroethane with Cl1 at 899>C ð38JA1388Ł[ Isotopically labeled CClF107F has been prepared by irradiation of a mixture of CClF2 and 07F08F[ CF207F was the main by!product ð68MI 596!90Ł[
"ii# Bromotri~uoromethane\ CBrF2 Bromotri~uoromethane may be synthesized in 89) yield under severe conditions "544Ð579>C# by treatment of tri~uoromethane with bromine ð35JA857\ 48USP1764143Ł or in 83) yield under milder conditions by ~uorination of tetrabromomethane at 9>C with BrF2 being added dropwise "Equation "07#\ Table 1# ð37JCS1077Ł[ Furthermore\ it can be made from tetrabromomethane with SbF2:Br1 at 199>C ð49USP1420261Ł or in low yield with TiF3 at 019>C ð47JCS3134Ł[ Individual products are separated from the reaction mixture by condensation in cold traps[ CBr4
BrF3, 0 °C
CF3Br
(18)
94%
Hofmann rearrangement of tri~uoroacetamide with sodium hypobromite does not yield tri! ~uoromethylamine\ but instead bromotri~uoromethane "Equation "08## ð46JCS29Ł[ This reaction is only useful for the generation of CBrF2 and cannot be used for CClF2 and CF2I ð43JA4030Ł[ Other degradative processes involve the Hunsdiecker reaction\ for example the heating of silver tri~uoroacetate and bromine at 54Ð029>C with formation of bromotri~uoromethane in 77) yield "Equation "19#^ Table 2# ð40JCS473\ 41JA0236Ł\ and the heating of tri~uoroacetyl bromide to 549>C causing elimination of carbon monoxide and formation of CBrF2 "Equation "10## ð44USP1693665Ł[ Bromination\ with elemental bromine\ of tri~uoroacetic acid at 439>C "Equation "11## or tri! ~uoroacetic acid anhydride at 299>C "Equation "12## in contact with activated carbon also leads to bromotri~uoromethane ð42USP1536822Ł[ NaOBr
CF3CONH2
CF3Br
(19)
CF3Br + CO2
(20)
CF3Br + CO
(21)
–NaNCO
CF3CO2Ag CF3COBr
65–130 °C
650 °C
Br2, activated charcoal
CF3CO2H
CF3Br + CO2
(22)
+ CO2
(23)
540 °C Br2, activated charcoal
(CF3CO)2O
CF3Br 300 °C
Bromotri~uoromethane has also been made by plasma chemical means[ The reaction conditions were applied for 3Ð4 min[ Thus\ treatment of hexa~uoroethane with bromine under the in~uence of high!frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 62) conversion and a 66) yield of CBrF2[ Treatment of CF2Cl under the same conditions gave only 12) conversion and a yield of 50) ð64ZAAC"307#098Ł[ As was the case with chlorotri~uoromethane\ bromotri~uoromethane is also formed upon bromination of hexa~uoroethane at 899>C ð38JA1388Ł[
108
Tetrahalomethanes
Bromotri~uoromethane may\ furthermore\ be prepared by Cl:Br exchange[ Thus\ treatment of CClF2 with HBr at 399>C in the presence of a ZnBr1:C catalyst leads to CBrF2 in 16) yield ð66BEP745122Ł[
"iii# Iodotri~uoromethane\ CF2I The preparation and reactions of per~uoroiodoalkanes have recently been reviewed by Deev et al[ ð81RCR64Ł[ Synthesis in high yield "80)#\ of iodotri~uoromethane is possible by the Hunsdiecker reaction\ for example from silver tri~uoroacetate and iodine\ and is used industrially "Equation "13## ð40JA1350\ 40JCS473Ł[ Sodium\ potassium\ barium\ mercury"II# and lead"II# tri~uoroacetate give in general lower yields of CF2I\ but the yield can be improved "79)# when sodium tri~uoroacetate is treated with excess iodine in the presence of CuI at 049>C in DMF ð56JOC722Ł or DMSO ð78MI 596!91Ł[ Other decomposition reactions have also been applied\ such as the heating of tri~uoroacetyl chloride with KI at 199>C for 5 h "Equation "14## giving 30) conversion and a yield of 58) iodo! tri~uoromethane under elimination of CO ð47JOC1905Ł\ or a procedure where tri~uoroacetyl ~uoride and lithium iodide at high temperature give CF2I in 69) yield "Equation "15## ð89CL702Ł[ CF3CO2Ag
I2
CF3I + AgI + CO2 91%
(24)
KI, 200 °C
CF3COCl
CF3I + KCl + CO 69%
6h
CF3COF
LiI
(25)
CF3I + LiF + CO 70%
(26)
In the laboratory\ iodotri~uoromethane may also be conveniently made from the commercially available methyl chlorodi~uoroacetate "Equation "16## which\ on the other hand\ can be prepared from CF1CF1 "Scheme 2#[ Thus\ treatment of CClF1CO1Me with equimolar potassium ~uoride and iodine at 099Ð019>C in DMF and in the presence of catalytic amounts of CuI gives a yield of 69Ð 79)[ CuI is essential for the high yield which in its absence drops to about 09)[ Omission of potassium ~uoride results in the formation of chlorodi~uoroacetamide in 03) yield as the only identi_ed product[ Furthermore\ substitution of methyl chlorodi~uoroacetate with the bromo ana! logue gives a yield of 69) upon heating to 79>C in DMF for 4 h ð81CC796Ł[ CuI (cat.) 100–120 °C, 2–3 h
CF3I + CF2I2 + CH3I + CO2 + KCl 80–90% (88:12)
ClCF2CO2Me + KF + I2 DMF
F F
F F
ICl
ClCF2CF2I
fuming H2SO4
ClCF2COF
MeOH
(27)
ClCF2CO2Me
Scheme 3
Other reactions include the reaction of tri~uoronitrosomethane with iodine at 49Ð69>C\ with a yield of 79Ð84) ð54IZV0762Ł\ and\ in low yield\ the ~uorination of CI3 with TiF3 ð47JCS3134Ł\ or with IF4 "Table 1# in a yield of 54) ð37JCS1077\ 38JCS1745Ł[ Due to the inferior reactivity of iodine penta~uoride compared to bromine tri~uoride\ the reaction requires heating at 89Ð099>C for 29 min[ Furthermore\ prolonged UV irradiation of methyl tri~uoromethyl sul_de or bis"tri~uoromethyl# sul_de in the presence of sources of iodine radicals yields 29Ð53) iodotri~uoromethane ð61JCS"P0#0495\ 63JCS"P0#0695Ł[ Iodotri~uoromethane can\ like bromotri~uoromethane\ be made by plasma chemical means "see the previous section#\ but only in modest yields[ Thus\ treatment of hexa~uoroethane with iodine
119
Four Halo`ens or Three Halo`ens and One Other Heteroatom
under the in~uence of high frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 29) conversion\ but only a yield of 4) CF2I[ Treatment of CF2Cl under the same conditions gave only 03) conversion but a yield of 17) ð64ZAAC"307#098Ł[
"iv# Tri~uoromethyliodine"III# compounds\ "CF2#nIZ2 −n "n 0\ 1# The preparation and isolation of CF2IF1 ð48AG413Ł\ CF2ICl1 ð78JFC"34#390Ł\ CF2I"ONO1#1 ð63IC1700Ł and CF2I"OCOCF2#1 ð65JFC"7#066Ł have been reported in the literature[ Tri~uoromethyliodine"III# di~uoride\ for instance\ is prepared by oxidative ~uorination "F1# at −79>C of tri~uoroiodomethane with trichloro~uoromethane as solvent ð48AG413Ł[ Bis"tri~uoromethyl#iodine derivatives "n 1\ Z ONO1\ OCOCF2\ F\ Cl# have been prepared by Tyrra and Naumann ð80CJC216Ł by tri~uoromethylation of tri~uoromethyliodine"III# dichloride\ dinitrate\ di~uoride or bis"tri~uoroacetate# with either Cd"CF2#1 = 1 glyme or Bi"CF2#2[ None of these were\ however\ isolated\ but only detected and investigated by NMR[
5[96[0[1[1 Trichloromethyl halides "i# Trichloro~uoromethane\ CCl2F Trichloro~uoromethane has been widely used as refrigerant and propellant and is known as Freon 00[ Industrial preparations include Cl:F exchange of HF with CCl3\ in a gas phase reaction at 049>C with catalysis from aluminum\ chromium\ nickel or calcium ~uoride[ The main by!product is Freon 01\ CCl1F1[ Alternatively\ the reaction may be conducted in the liquid phase under pressure at 099>C and with antimony ~uoride catalysis ð45USP1628878\ B!82MI 596!91Ł[ The product of the reaction between tetrachloromethane and HF is highly dependent on the relative amounts of CCl3 and HF as well as on the temperature[ At an HF ] CCl3 ratio of 0 ] 8\ a temperature of 324>C and a pressure of 69 atm\ the total yield is 84)\ consisting of 66) CCl2F\ 07) CCl3 and 4) CCl1F1 "Equation "17## ð36IEC393Ł[ In liquid phase reactions antimony chlorides\ such as SbCl2\ together with a certain amount of chlorine or even better\ SbCl4 have been used ð36JA836Ł[
CCl4 + HF
cat. 435 °C, 70 atm
CCl3F + CCl4 + CCl2F2
(28)
95% (77:18:5)
Trichloro~uoromethane is also formed as one of the minor products in the reaction of graphite with Cl1 and HF at 499>C as described above ð44USP1698073Ł[ Sodium hexa~uorosilicate under pressure at 169>C "Equation "18## ð48AG163Ł\ titanium tetra! ~uoride ð47JCS3134Ł\ chlorine tri~uoride:cobalt tri~uoride at 14>C ð42JCS0952Ł\ iodine penta~uoride at 29Ð24>C ð20ZAAC"190#134Ł and bromine tri~uoride "Table 1\ Equation "29## ð37JCS1077Ł are also useful as ~uorinating agents for tetrachloromethane[
CCl4 + Na2SiF6
autoclave 270 °C, 2 h
CCl3F + CCl2F2 + CClF3 + NaCl + SiF4
(29)
~100% (33:66:trace)
CCl4 + BrF3 (1:0.33)
RT
CCl2F2 + CCl3F
(30)
61% (5:95)
In the laboratory the Hunsdiecker reaction may be applied for the synthesis of trichloro! ~uoromethane "in 52) yield# from silver dichloro~uoroacetate and chlorine "Table 2\ Equation "20## ð41JCS3148Ł[
110
Tetrahalomethanes CCl2FCO2Ag + Cl2
180–260 °C
CCl3F + CO2 + AgCl
(1:1.5)
(31)
63%
"ii# Bromotrichloromethane\ CBrCl2 Treatment of tetrachloromethane with HBr:AlBr2 leads to bromotrichloromethane ð23JA0344Ł[ Bromotrichloromethane is formed by treatment of trichloromethane with bromine at 114Ð349>C ð26CR"193#0816\ 36JCS563Ł\ or in 79Ð74) yield at 319Ð349>C by recycling the material with b[p[ below 64>C ð41MI 596!90Ł\ and\ furthermore\ under the in~uence of light ð31JA0231Ł[ Older methods involve heating potassium trichloroacetate with bromine at 019>C "Equation "21#\ Table 2# ð0766CB567Ł or heating trichloromethanesulfonyl bromide with ethanol at 099>C ð0758ZC513Ł[ Low yields "09)# of bromotrichloromethane have been achieved by heating tri! chloroacetyl bromide to 399>C[ Most of the trichloroacetyl bromide was recovered "Table 2# ð28JA324Ł[ Cl3CCO2K + Br2
110–120 °C >70%
CBrCl3 + CO2 + KBr
(32)
The less easily available tetrahalomethanes may\ however\ also be prepared by base!catalyzed {{halogen dance|| "Scheme 3# ð81MI 596!92\ 82BSF488Ł[ Heating chloroform with tetrabromomethane and dibenzoyl peroxide ð40USP1442799Ł or N! bromosuccinimide ð41MI 596!91Ł also yields bromotrichloromethane[ base
CBrCl3
CCl4 + CBr2Cl2 + CBr3Cl + CBr4 base/solvent
F3CCCl3 + CBr4 RT, 0.5–11 h
F3CCBrCl2 + F3CCBr2Cl + F3CCBr3 + CBrCl3 + CBr2Cl2 + CBr3Cl solvent: DMF, CH2Cl2 base: TBAF, NaOPh, NaOH, KOH, NaOEt, NaNH2 Scheme 4
"iii# Trichloroiodomethane\ CCl2I Good yields "64)# of trichloroiodomethane in admixture with hexachloroethane "05)# are achieved by distillation "039>C# at atmospheric pressure of trichloroacetyl iodide "Scheme 4\ Table 2# ð28JA324Ł\ prepared from hydrogen iodide and trichloroacetyl chloride[ Treatment of bromotrichloromethane with aluminum iodide leads to trichloroiodomethane ð42JCS811Ł[
Cl3CCOCl
HI
Cl3CCOI
distillation 140 °C
Cl3CCCl3 + CCl3I 80% (6:94)
Scheme 5
Trichloromethane treated with iodine and sodium hydroxide at 9>C for 04 h\ gave 09) di! chloroiodomethane as well as 0) trichloroiodomethane[ The iodinating agent in this medium is sodium hypoiodite generated in situ[ Use of tetrachloromethane\ excess iodine and sodium hydroxide at 9>C for _ve days gave trichloroiodomethane in less than 4) yield[ An attempt to iodinate tetrachloromethane with NaI in acetone failed ð68JCED140Ł[
111
Four Halo`ens or Three Halo`ens and One Other Heteroatom
5[96[0[1[2 Tribromomethyl halides "i# Tribromo~uoromethane\ CBr2F Tribromo~uoromethane is formed as a coproduct "20)# in the reaction of "dibromo! ~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CFBr2 in THF\ with iodine monobromide in tetraglyme "Scheme 5# ð71JFC"19#78Ł\ and under controlled reaction conditions\ in high yield "83)# upon ~uorination of tetrabromomethane with bromine tri~uoride "Equation "22#\ Table 1# ð37JCS1077Ł[ R3P + CFXYZ
solvent
[R3PCFXY]+ Z– + X'Y' + KF
[R3PCFXY]+ Z– solvent'
CFXYX'
solvent = THF, diethyl ether or triglyme solvent' = triglyme, tetraglyme or DMF R = Ph or (NMe2) X, Y, Z = F, Cl or Br X', Y' = Cl, Br, I Scheme 6
CBr4
+ BrF3
~0 °C
(1:0.33)
CBr3F + CBr2F2 94% (100:trace)
(33)
Furthermore\ it is available by ~uorination of tetrabromomethane with antimony tri~uoride "08Ð81) yield# ð07CB558\ 46JA4543\ 47BSB565\ 48JCS02Ł[ Birchall and Haszeldine heated tetrabromo! methane with antimony tri~uoride and bromine "1 ] 0 ] 9[0# 0 h at 019Ð029>C\ followed by 29 min at 049Ð059>C\ with a yield of 54Ð69) after distillation "Equation "23## ð48JCS02Ł[ Silver ~uoride has also been applied as ~uorinating agent in a distillation apparatus*allowing bromotri~uoromethane to distil out of the reaction mixture ð07CB558Ł[ CBr4 + Br2 + SbF3 (2:0.1:1)
i, 120–130 °C, 1 h ii, 150–160 °C, 0.5 h
CBr3F 65–70%
(34)
"ii# Tribromochloromethane\ CBr2Cl Tribromochloromethane is formed as the main product "relative yield 31)# after base!catalyzed {{halogen dance|| reactions "Scheme 3# ð81MI 596!92\ 82BSF488Ł[ Thus\ after treatment of CF2CCl2:CBr3 with KOH in DMF at RT for 3 h\ tribromochloromethane is formed with the following by!products] CF2CCl1Br "relative yield 21)#\ CF2CClBr1 "10)# and CBr1Cl1 "08)# ð81MI 596!92Ł[ Dibromochloronitrosomethane may be re~uxed with bromine for 2 h giving a 84) yield of tribromochloromethane[ Dibromochloronitrosomethane is in turn accessible from Br1C1NOH "Scheme 6# ð21CB435Ł[ Br
OH N
Br
i, HgCl2 (aq.) ii, Br2, NaOAc
ClBr2CNO 75–80%
Br2, reflux, 3 h
CBr3Cl 95%
Scheme 7
Treatment of CCl3 with an equimolar amount of Br1 for 1 h at 114>C leads to tri! bromochloromethane in admixture with bromotrichloromethane and dibromodichloromethane ð0781CB077Ł[ Trichloromethane heated with bromine for 03 h at 114Ð164>C ð26CR"193#0816Ł as well as HBr:AlCl2 treatment of tetrachloromethane gives tribromochloromethane[ In the latter reaction\ HBr is bubbled into a solution of CCl3 and AlCl2 and the temperature raised to 89>C[ The product contains 5) tribromochloromethane and 83) tetrabromomethane with an 76) conversion of tetrachloromethane[
Tetrahalomethanes
112
"iii# Tribromoiodomethane\ CBr2I Treatment of CHBr2 with KI\ NaOCl and NaOH for 13 h gave mainly CHBr1I "09)# and only traces "9[0)# of tribromoiodomethane could be detected[ The same reaction conditions were also applied to CBr3 for six days\ but again only a very low yield "³0)# of CBr2I was obtained[ On the other hand\ when CBr3 was treated with NaI in acetone for 4 min a yield of more than 29) CBr2I was observed\ although the product was contaminated with CBrI2 and brominated acetone "Equation "24## ð68JCED140Ł[ According to an old procedure by Dehn ð98JA0119Ł it should\ however\ be possible to prepare tribromoiodomethane from tribromomethane and nitrosyl iodide[ Dehn reported the product as a solid darkening at 24>C[ NaI, acetone
CBr4 5 min
CBr3I + CBrI3 + brominated acetone ~30%
(35)
5[96[0[1[3 Triiodomethyl halides "i# Fluorotriiodomethane\ CFI2 and chlorotriiodomethane\ CClI2 Fluorotriiodomethane and chlorotriiodomethane still await preparation\ but theoretical dis! cussions of their physical properties are on record ð47MI 596!90\ 48MI 596!92\ 55ZOB0244\ 61MI 596!90\ 65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\ 80MI 596!90Ł[
"ii# Bromotriiodomethane\ CBrI2 Bromotriiodomethane has been prepared by Dehn ð98JA0119Ł by treatment of triiodomethane with NaOBr[ It is an unstable solid which liberates iodine upon exposure to light or upon dissolution[ Bromotriiodomethane has also been reported as a by!product in the Finkelstein reaction mentioned above\ that is the treatment of tetrabromomethane with sodium iodide in acetone "Equation "24## ð68JCED140Ł[
5[96[0[2 Two Similar Halogens 5[96[0[2[0 Di~uoromethylene dihalides "i# Bromochlorodi~uoromethane\ CBrClF1 Bromochlorodi~uoromethane may be prepared in 80) yield by the heating of silver chloro! di~uoroacetate with bromine "Equation "25#\ Table 2# ð41JCS3148Ł[ CClF2CO2Ag + Br2 (1:1.5)
180–260 °C
CBrClF2 + CO2 + AgBr
(36)
91%
Bromochlorodi~uoromethane is formed\ but only in very low yield "4)#\ in the reaction of tris"dimethylamino#"chlorodi~uoromethyl#phosphonium chloride\ formed from tris"dimethyl! amino#phosphine and CF1Cl1 in triglyme\ with bromine in triglyme "Scheme 5# ð71JFC"19#78Ł[ Trabalka et al[ describe in a patent ð70MIP57244Ł the formation of bromochlorodi~uoromethane by heating of chlorodi~uoromethane with bromine and chlorine at 499Ð799>C[ Other synthetic methods include the preparation from chlorodi~uoromethane\ bromine and oxygen with catalysis from chromium trioxide at 499>C[ The yield was 75) and the reaction product consisted of CBrClF1\ CBr1F1 and CHClF1 "47 ] 6 ] 24^ Equation "26## ð48USP1760163Ł[ Other sources are bro! modi~uoromethane by vapor phase chlorination ð42USP1528291Ł or UV irradiation of a mixture of
113
Four Halo`ens or Three Halo`ens and One Other Heteroatom
chlorodi~uoroiodomethane and bromine ð41JCS3148Ł[ Finally\ treatment of 0\2!dichloro!0\0\2\2! tetra~uoroacetone with bromine at 479Ð549>C yields bromochlorodi~uoromethane ð48USP1774349Ł[ CHClF2 + Br2 + O2
CrO3 500 °C
CBrClF2 + CBr2F2 + CHClF2
(37)
86% (58:7:35)
"ii# Chlorodi~uoroiodomethane\ CClF1I Chlorodi~uoroiodomethane has been prepared by Haszeldine "Equation "27#\ Table 2# ð41JCS3148Ł in 67) yield by heating silver chlorodi~uoroacetate with iodine[ This halomethane is\ however\ unstable and liberates iodine on exposure to O1 or light ð41JCS3148Ł[ CClF2CO2Ag + I2 (1:1.5)
180–260 °C
CClF2I + CO2 + AgBr 78%
(38)
Di~uorocarbene is generated from methyl chlorodi~uoroacetate by treatment with LiCl:HMPA and may\ when formed in the presence of I1 or IBr\ be used to prepare chlorodi~uoroiodomethane in 04) yield "contaminated with 4) CF1I1# and 29) "contaminated with 09) CBrF1I#\ as shown in Equations "28# and "39#\ respectively ð67JOC1532Ł[
CClF2CO2Me + LiCl/HMPA + I2
90–95 °C, 48 h triglyme
CClF2I + CF2I2
(39)
20% (75:25)
CClF2CO2Me + LiCl/HMPA + IBr
90–95 °C, 48 h triglyme
CClF2I + CBrF2I 40% (75:25)
(40)
Another method is the reaction of ð"Me1N#2P"CF1Cl#ŁCl\ formed from tris"dimethylamino#! phosphine and CF1Cl1 in triglyme\ with dry potassium ~uoride and iodine at 9>C for 1 h and then overnight at room temperature[ The isolated yield of CClF1I is 23) "Scheme 5# ð71JFC"19#78Ł[ Chlorodi~uoroiodomethane can\ like bromo! and iodotri~uoromethane\ be made by plasma chemical means\ but only in modest yields[ Thus\ treatment of chlorotri~uoromethane with iodine under the in~uence of high!frequency electrical discharges "01 MHz\ 0 kV# at 3Ð19 torr gave 6) conversion\ and a relative yield of 10) ð64ZAAC"307#098Ł[
"iii# Bromodi~uoroiodomethane\ CBrF1I When di~uorocarbene is generated in the presence of IBr\ bromodi~uoroiodomethane is formed as a by!product "09)# "Equation "39## ð67JOC1532Ł[ Another method is the reaction of "bromo! di~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CF1Br1 in triglyme\ with dry potassium ~uoride and iodine in triglyme[ The isolated yield of CBrF1I is 30) "Scheme 5# ð72JFC"12#228\ 71JFC"19#78Ł[ Bromodi~uoroiodomethane is one of the few tetrahalomethanes which could not be prepared except in poor yield "³4)# by the Hunsdiecker method "Table 2#[
5[96[0[2[1 Dichloromethylene dihalides "i# Dichlorodi~uoromethane\ CCl1F1 The industrial preparation of dichlorodi~uoromethane\ known as Freon 01\ involves halogen exchange of CCl3 with HF\ as described above for CFCl2 ðB!82MI 596!91Ł[ At a HF ] CCl3 ratio of 3 ] 8\ a temperature of 389>C and a pressure of 69 atm\ the total yield in the reaction between CCl3 and HF has been reported to be 48)\ consisting of 68) CCl1F1 and
114
Tetrahalomethanes
10) CCl2F "Equation "30## ð36IEC393Ł\ whereas in the presence of SbCl2 and Cl1 at 009>C and 29 atm\ CCl1F1 constitutes 89) of the product ðB!81MI 596!93Ł[ Furthermore\ treatment of phosgene with chlorine and anhydrous hydrogen ~uoride at 314>C in the presence of FeCl2:C also yields a mixture consisting of CCl1F1\ CClF2 and CF3 "Equation "06## ð46JA4790Ł[ Trichloromethane does\ as mentioned above\ also form a CClmFn mixture when treated with CF2OF ð48JA0978Ł\ and dichlorodi~uoromethane is formed as one of the minor products in the reaction of graphite with Cl1 and HF at 499>C as described above ð44USP1698073Ł[ 490 °C, 70 atm
CCl4 + HF (9:4)
CCl2F2 + CCl3F 59% (79:21)
(41)
In the laboratory\ dichlorodi~uoromethane may be prepared in high yield "85)# by ~uorination of CCl2F with BrF2\ or as the main product of the ~uorination of CCl3 with BrF2 at −67>C:RT in a total yield of 78) "Scheme 7\ Table 1#[ Trichloro~uoromethane is the only by!product ð20USP0850511\ 37JCS1077Ł[ CCl4 + BrF3
–78 °C to RT
(1:0.6) RT
CCl4 + BrF3 (1:0.8)
CCl2F2 + CCl3F 89% (85:15) CCl2F2 96%
Scheme 8
Treatment of tetrachloromethane with sodium hexa~uorosilicate under pressure at 169>C in an autoclave yields a mixture of CClnF3−n with dichlorodi~uoromethane as the major product "Equa! tion "18## ð48AG163Ł[ Degradative reactions forming CCl1F1 include the chlorinolysis at 449>C of 0\0!di~uoroethane\ formed by treatment of acetylene with HF ðB!48MI 596!91Ł and the heating of silver chloro! di~uoroacetate with chlorine "Equation "31#\ Table 2# ð41JCS3148Ł[ CClF2CO2Ag + Cl2
180–260 °C
(1:1.5)
CCl2F2 + CO2 + AgCl 88%
(42)
Dichlorodi~uoromethane may _nally also be made by electrolysis of chlorodi~uoroacetic acid ð22BSB091Ł[
"ii# Bromodichloro~uoromethane\ CBrCl1F Bromodichloro~uoromethane has been prepared by Haszeldine ð41JCS3148Ł by use of the Hunsdiecker reaction\ in 47) yield by heating silver dichloro~uoroacetate with bromine "Equation "32## and in 52) yield by heating silver bromochloro~uoroacetate with chlorine "Equation "33#\ Table 2#\ and also by bromination of dichloro~uoromethane at 364>C "30) conversion\ yield 67)# ð45USP1644203\ 46JA3048\ 48JA1967Ł[ CCl2FCO2Ag + Br2
180–260 °C
(1:1.5) CBrClFCO2Ag + Cl2 (1:1.5)
180–260 °C
CBrCl2F + CO2 + AgBr 58%
(43)
CBrCl2F + CO2 + AgCl 63%
(44)
"iii# Dichloro~uoroiodomethane\ CCl1FI Dichloro~uoroiodomethane has been prepared in poor yield by heating silver dichloro! ~uoroacetate with iodine[ Dichloro~uoroiodomethane turned out to be unstable to storage at RT[ It forms di}erent haloethanes with liberation of iodine ð41JCS3148Ł "Table 2#[ It has been prepared in 33) yield "52Ð62) yield according to Fried and Miller ð48JA1967Ł# by a
115
Four Halo`ens or Three Halo`ens and One Other Heteroatom
Finkelstein reaction from bromodichloro~uoromethane:NaI:acetone in a closed vessel for 2 h at 019>C "Equation "34## ð46JA3048Ł[ CBrCl2F + NaI
acetone 120 °C, 3 h
CCl2FI + NaBr 44–73%
(45)
"iv# Bromodichloroiodomethane\ CBrCl1I Bromodichloroiodomethane has not been prepared yet\ but theoretical discussions of its physical properties are on record ð61MI 596!90\ 68JMR448\ 80MI 596!90Ł[
5[96[0[2[2 Dibromomethylene dihalides "i# Dibromodi~uoromethane\ CBr1F1 Dibromodi~uoromethane may be prepared in 72) as the only product by ~uorination of tetra! bromomethane with IF4 "Equation "35##\ as the major product "relative yield 65)# by ~uorination with BrF2\ and as a minor product "relative yield 05)# by ~uorination of tetraiodomethane with IF4 "Table 1# ð37JCS1077Ł[ Fluorination of tetrabromomethane with TiF3 forms dibromo! di~uoromethane in low yield as a mixture with bromotri~uoromethane ð47JCS3134Ł[ Furthermore\ CBr1F1 is formed in high yield "70)# by the heating of silver bromodi~uoroacetate with bromine "Equation "36#\ Table 2# ð41JCS3148Ł[ CBr4 + IF5 (1:0.6)
90 °C, 3 h
CBrF2CO2Ag + Br2 (1:1.5)
CBr2F2 + CBr3F + CBrF3 + CF4 83% (100:trace:trace:trace) 180–260 °C
CBr2F2 + CO2 + AgBr 81%
(46)
(47)
Other methods involve vapor phase bromination of di~uoromethane at 499>C "50) conversion^ the product is a mixture of CHBrF1 and CBr1F1 ð42USP1528290Ł# and treatment of di~uoromethane with a mixture of bromine and chlorine at 249>C ð42USP1547975Ł[ Furthermore\ a low yield is obtained from bromochlorodi~uoromethane and HBr:Br1 at 599>C "55) conversion^ the product is a 83 ] 5 mixture of CHBrF1 and CBr1F1 ð45USP1618576Ł#\ or from tribromo~uoromethane\ HF and a chromium oxo~uoride catalyst at 149>C ð45USP1634775Ł[ Reaction between tetrabromomethane\ HF and an aluminum oxo~uoride catalyst at 129Ð149>C\ 0\2!dichloro!0\0\2\2!tetra~uoroacetone and bromine at 479Ð549>C ð48USP1774349Ł or the heating of tetrabromomethane with AgF "0 ] 1#\ allowing distillation from the reaction mixture to occur ð07CB558Ł\ all lead to dibromodi~uoro! methane[ Dibromodi~uoromethane is formed\ but only in a very low yield "2)#\ in the reaction of tris! "dimethylamino#"chlorodi~uoromethyl#phosphonium chloride\ formed from tris"dimethylamino#! phosphine and CF1Cl1 in triglyme\ with bromine in triglyme "Scheme 5# ð71JFC"19#78Ł[
"ii# Dibromodichloromethane\ CBr1Cl1 Bromotrichloromethane disproportionates in the presence of tetrabutylammonium ~uoride to a mixture of tetrachloromethane\ dibromodichloromethane\ tribromochloromethane and tetra! bromomethane ð82BSF488Ł[ Other bases and solvent systems have also been tried in such base! catalyzed {{halogen dance|| reactions[ The individual halomethanes were obtained by fractional distillation "Scheme 3# ð81MI 596!92Ł[ It is also obtained\ in admixture with other halomethanes\ from tetrachloromethane treated with bromine tri~uoride in the presence of AlCl2 or BBr2[ Dichloromethane and bromine react under formation of dibromodichloromethane on illumi! nation ð31JA0231Ł or after heating in a sealed vessel at 119Ð149>C for more than a week
116
Tetrahalomethanes
ð0776LA"139#081Ł[ Furthermore\ impure CBr1Cl1 is obtained upon treatment of trichloromethane with bromine in a closed reaction vessel at 114Ð164>C ð26CR"193#0816Ł or by heating dichloro! bromonitrosomethane with bromine "vide supra# ð21CB435Ł[
"iii# Dibromochloro~uoromethane\ CBr1ClF Dibromochloro~uoromethane is formed in 60) yield upon heating of silver bromo! chloro~uoroacetate with bromine "Equation "37#\ Table 2# ð41JCS3148Ł and by vapor phase bro! mination of dichloro~uoromethane at 549>C ð45USP1644203Ł[ CBrClFCO2Ag + Br2 (1:1.5)
180–260 °C
CBr2ClF + CO2 + AgBr 71%
(48)
"iv# Dibromo~uoroiodomethane\ CBr1FI Dibromo~uoroiodomethane is formed as the major product "46)# in the reaction of "dibromo! ~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CBr2F in THF\ with iodine in tetraglyme[ The crude product is\ however\ contaminated with substantial amounts of other halomethanes "Scheme 5# ð71JFC"19#78Ł[
"v# Dibromochloroiodomethane\ CBr1ClI Dibromochloroiodomethane still awaits preparation\ but theoretical discussions of its physical properties are on record ð61MI 596!90\ 68JMR448\ 80MI 596!90Ł[
5[96[0[2[3 Diiodomethylene dihalides "i# Di~uorodiiodomethane\ CF1I1 Di~uorodiiodomethane has been prepared in low yield "16)# by ~uorination of CI3 with HgF1 in 0\1!dichlorobenzene[ Excessive ~uorination is minimized by distillation of the CF1I1 formed in the reaction ð73JOC194\ 74DIS"B#739Ł[ A better method has\ however\ been reported by Su et al[ ð81CC796Ł who discovered a convenient method for obtaining pure CF1I1 in fair yield "49Ð59) isolated yield^ 79) by 08F NMR#[ Treatment of methyl bromodi~uoro! or chlorodi~uoroacetate with equimolar amounts of KI\ I1 and a catalytic amount of CuI leads to the formation of CF1I1 "Equation "16##[ This method is\ however\ somewhat compromized by di.culties in the separation of CH2I and CF1I1[ Pure di~uorodiiodomethane is obtained from potassium bromodi~uoroacetate by heating with equimolar amounts of KI\ CuI and I1 in DMF at 39>C for 09 h[ The use of only a catalytic amount of CuI causes the yield to drop to 09) "Equation "38## ð81CC796Ł[
CBrF2CO2K + KI + CuI + I2
DMF 40 °C, 10 h
CF2I2 + KBr + CO2 90% (50–60% isolated)
(49)
"ii# Dichlorodiiodomethane\ CCl1I1 Dichlorodiiodomethane has been prepared by Holand in 0776 ð0776LA"139#114Ł by treatment of CH1Cl1 with Br1:I1 "0 ] 3:3# at 099Ð199>C for several weeks[ Distillation of the crude product gave dichloroiodomethane and dichlorodiiodomethane[ Dichlorodiiodomethane melts at 74>C under liberation of iodine and is probably unstable in solution ð0776LA"139#114Ł[
117
Four Halo`ens or Three Halo`ens and One Other Heteroatom
"iii# Bromo~uorodiiodomethane\ CBrFI1 Bromo~uorodiiodomethane is formed as a minor by!product "04)# in the reaction of "dibromo! ~uoromethyl#triphenylphosphonium bromide\ formed from triphenylphosphine and CBr2F in THF\ with iodine in DMF "Scheme 15# ð71JFC"19#78Ł[
"iv# Dibromodiiodomethane\ CBr1I1^ chloro~uorodiiodomethane\ CClFI1^ and bromochlorodiiodomethane\ CBrClI1 Dibromodiiodomethane\ chloro~uorodiiodomethane and bromochlorodiiodomethane still await preparation\ but theoretical discussions of their physical properties are on record ð47MI 596!90\ 48MI 596!92\ 55ZOB0244\ 61MI 596!90\ 65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\ 80MI 596!92Ł[
5[96[0[3 Bromochloro~uoroiodomethane\ CBrClFI Bromochloro~uoroiodomethane\ although often mentioned as the prototype of a chiral compound\ has not been prepared yet[ MO calculations indicate that it is the second least stable chiral halomethane judged from the enthalpies of formation ð89BCJ0167Ł[ The only chiral halo! methane which has been prepared is CHBrClF\ and it has been shown that this derivative hydrolyzes much faster than other mixed halomethanes ð45JA368Ł^ this may also be the case with bromo! chloro~uoroiodomethane[ It would be interesting to try the Hunsdiecker reaction on silver bromochloro~uoroacetate which reacts with both chlorine and bromine as mentioned above[ It may\ however\ turn out to be a very low yielding reaction\ as was the case with the treatment of silver bromodi~uoroacetate with iodine "Table 2# ð41JCS3148Ł[ Theoretical discussions of the physical properties of so far unsynthesized tetrahalomethanes are on record ð47MI 596!90\ 48MI 596!90\ 55ZOB0244\ 61MI 596!90\ 65ZC266\ 66MI 596!90\ 68JMR448\ 72MI 596!90\ 80MI 596!90Ł[
5[96[1 METHANES BEARING THREE HALOGENS 5[96[1[0 Three Halogens and a Chalcogen Trihalomethoxy as well as trihalomethylthio groups may be regarded as superhalo`ens and behave as such[ They are\ for example deactivating and ortho!\ para!directing substituents in electrophilic aromatic substitution[ As superhalo`ens\ they have been used as alternative substituents to cir! cumvent existing patents and to impart increased lipophilicity to compounds relative to their halogen substituted counterparts[ For more information see a comparison and discussion on trihalomethyl "and other pseudohalogens# vs[ halogen by Haas\ who has made a large contribution to this synthetic _eld ð71CZ128\ 73MI 596!90Ł[ The subject of trihalomethoxy and trihalomethylthio containing compounds has previously been reviewed by Marhold ð72HOU"E3#514\ 72HOU"E3#0192Ł\ Hocker ð72HOU"E3#0257Ł and McClinton and McClinton ð81T5444Ł[
5[96[1[0[0 Three halogens and an oxygen function "i# Trihalomethanols\ CHal2OH Tri~uoromethanol is a rather unstable compound which\ above −19>C\ eliminates hydrogen ~uoride under formation of carbonyl ~uoride[ It was therefore not synthesized until 0866\ when Seppelt prepared tri~uoromethanol by treating tri~uoromethyl hypochlorite with HCl at −019>C ð66AG214Ł[
Three Halo`ens
118
"ii# Trihalomethyl ethers\ CHal2OR Aryl tri~uoromethyl ethers may be prepared from the corresponding phenols by treatment with tetrachloromethane and hydrogen ~uoride\ with the exception of phenols with ortho!substituents capable of hydrogen bonding to the hydroxy group[ The yields are generally best when electron! withdrawing substituents are present ð68JOC1896Ł[ Chlorine may be used as such and later removed by hydrogenation ð76JA2697Ł[ The reaction is catalyzed by antimony trichloride and probably passes through the trichloro derivative ð68JOC1896Ł[ Trichloromethyl ethers "aryl and alkyl# can in turn be transformed to tri~uoromethyl ethers by treatment with F1:SnF1 ð80CL0310Ł\ HF ð75BSF814Ł\ HF:SbCl4 ð61GEP1018199Ł\ SbF2 ð44DOK"094#099Ł or even better SbF2:SbCl4 ð47JGU1428Ł[ Mixed trihalomethyl ethers may be prepared by decreasing the reaction temperature and the amount of HF "HF:SbCl2# used ð61GEP1018199\ 68JOC1896\ 75BSF814Ł[ Rico and Wakselman made mixed trihalomethyl ethers from potassium phenoxides\ CBr1F1 or CBrClF1 and a catalytic amount of 0!propanethiol kept in DMF at RT for 3 h[ Unfortunately\ low yields "5Ð49)# were obtained with aryl di~uoromethyl ethers as the major and aryl bromo! di~uoromethyl ethers as the minor product ð70T3198Ł[ Synthesis of aryl trichloromethyl ethers from the corresponding nonhalogenated ether is achieved by photochlorination "69) yield# or by use of Cl1:PCl4 "60) yield# ð66CI"L#016\ 75BSF814Ł[ A carbonyl function can be regarded as a latent CF1 function[ The corresponding transformation is e}ected by SF3\ sometimes in the presence of HF[ Other reagents include the more easily handled alkylsulfur tri~uorides\ MoF5:BF2\ COF1 or the more reactive SeF3 ðB!81MI 596!90Ł[ According to Hudlicky ðB!81MI 596!90Ł the following order of reactivity is observed with SF3 as ~uorinating agent] alcohols×aldehydes\ ketones×acids\ amides×esters\ acid anhydrides×alkyl halides[ This has been exploited in the synthesis of tri~uoromethyl ethers[ Thus\ treatment of ~uoroformic acid esters "FC"1O#OR# with sulfur tetra~uoride leads to tri~uoromethyl ethers[ This reaction is especially convenient for the synthesis of aryl tri~uoromethyl ethers\ and only when electron! withdrawing groups are present in the b!position can the aliphatic counterparts be synthesized in satisfactory yields ð50JA3759\ 53JOC0\ 53JOC00Ł[ Analogous to this O!alkyl chlorothioformic acid esters "ClC"1S#OR# can also be transformed to tri~uoromethyl ethers by treatment with MoF5\ in 39Ð89) yield ð62TL1142Ł[ Trichloromethyl ethers are prepared similarly by chlorination with Cl1 of ZC"1S#OR "Z Cl\ SMe# and ðROC"1S#SŁ1 ð44JA0788\ 45JA5969\ 47JGU1428\ 47ZOB1495\ 53ZOB0868\ 61JOC1540Ł[ A very mild method for the transformation of xanthates or "di~uoro"methylthio#methyl# ethers into tri~uoromethyl ethers was introduced by Kuroboshi et al[ They made use of "HF#8: pyridine:0\2!dibromo!4\4!dimethylhydantoin "DBH# as oxidative desulfurization!~uorinating agent and achieved yields of 37Ð79) ð81TL3062Ł[ Electrophilic addition of halogens to alkenes is a standard reaction in organic chemistry\ and addition of trihalomethyl hypohalites\ which may be considered as a halogen bound to a super! halogen\ should therefore be expected to constitute a similar reaction\ which is exactly the case[ Thus\ b!~uoro! or b!chloroalkyl tri~uoromethyl ethers may be prepared by addition of tri~uoromethyl hypo~uorite or hypochlorite to alkenes[ The reaction of tri~uoromethyl hypochlorite with unsubstituted alkenes can be controlled at temperatures below −000>C\ whereas the reaction with electron!poor alkenes only proceeds at a signi_cantly higher temperature "½49>C#[ The addition is most probably polar in nature\ with Markovnikov regiochemistry\ and gives syn!addition products[ Tri~uoromethyl hypo~uorite\ on the other hand\ is more reactive and its reactions have to be conducted at much lower temperature[ They are most probably of free!radical nature\ that is anti!Markovnikov and lack stereoselectivity[ The yields are in most cases quantitative ð72JOC131\ 75IC265\ 80CL0310Ł[ Bis"tri~uoromethyl# and bis"trichloromethyl# ether are prepared from dimethyl ether by electro! ~uorination "HF# ð49USP1499277Ł and photochlorination "Cl1# ð47CT404Ł\ respectively[ Tri~uoromethoxide is a rather poor nucleophile but\ with tris"dimethylamino#sulfonium ""Me1N#2S¦^ TAS¦# as counterion\ nucleophilic substitution is possible[ Fluorination instead of tri~uoromethoxylation may\ however\ be expected at secondary substitution sites due to the elevated reaction temperature required ð74JA3454\ 74MI 596!90Ł[ Transformation of an enol group into a di~uorohalomethoxy group has been accomplished by reaction with di~uorocarbene[ Thus\ 5!substituted 1!quinoxalones upon treatment with dibromo! di~uoromethane gave 5!substituted 1!"bromodi~uoromethoxy#quinoxalines[ Further treatment with poly"hydrogen ~uoride#:pyridine yields the corresponding tri~uoromethyl ethers "Scheme 8# ð81JFC"48#306Ł[ A summary of selected methods for the synthesis of trihalomethyl ethers is found in Table 3[
129
Four Halo`ens or Three Halo`ens and One Other Heteroatom
R
N
N
R
R
CBr2F2
N H
N
poly (HF)/pyridine
O
N
OCBrF2
N
OCF3
+ N
R
N
OCHF2
R = H, OMe, CF3, Cl Scheme 9
Table 3 Selected methods for the formation of trihalomethyl ethers[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Startin` material Rea`ent"s# Reaction conditions Product"s# Ref[ "yield# ")# ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Ar0OH CCl3:HF 049>C\ 7 h Ar0OCF2 "09Ð62# 68JOC1896 R0OCCl2 R aryl or alkyl
HF:SbCl4
039>C\
R0OCF2 "64Ð75#
61GEP1018199
Cl1:hn Cl1:PCl4
79>C\ 089Ð199>C\
Ar0OCCl2 "69# "60#
66CI"L#016 75BSF814
SF3
099Ð064>C\ 5 h
R0OCF2 "07Ð61#
53JOC0 53JOC00
Cl1
9:49>Ca
R0OCCl2 "14Ð89#
"see text#
−14Ð029Ð089>C
"39Ð89#
62TL1142
Ar0OMe
R0OC"1O#F R aryl or alkyl R0OC"1S#Z Z Cl\ SMe\ SSC"1S#OR R aryl or alkyl
MoF5 b
R0OC"1S#SMe R aryl or alkyl
Poly!HF:pyridine:DBH
−67Ð9>C\ 0 h
R0OCF2 "49Ð79#
81TL3062
CR11CR1
CF2OF CF2OCl
varying
CF2O0CR10CR10F CF2O0CR10CR10Cl "½quant[#
80CL0310 75IC265 72JOC131
R0OCF2 ] R0F 74MI 596!90 R0OTf CF2O−TAS¦c R alkyl "77\ 61 ] 17#d 74JA3454 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a Depending on the actual compound type[ b DBH\ 0\2!dibromo!4\4!dimethylhydantoin[ c TAS¦\ tris"dimethylamino#sulfonium[ d This ratio "tri~uoromethoxylation vs[ ~uorination# was achieved at a secondary site[ Milder conditions may be used at primary sites which favor tri~uoromethoxylation[
"iii# Trihalomethyl esters\ CHal2OC"1O#R Trihalomethyl esters may be considered as carboxylic acid superhalides and therefore expected to be very reactive[ They may\ furthermore\ be expected to be thermally unstable and to release carbonyl dihalide with formation of the corresponding carboxylic acid halide\ as is the case with trichloromethyl perhalobutanoic acid esters ð58CB2016Ł[ Only very few compounds containing a CHal2ZC"1Z?#R "Z\ Z? O\ S\ Se\ Te# substructure are known[ They are in general formed by halogenation of the corresponding methyl esters[ Thus\ aerosol ~uorination of methyl per~uoroadamantaneacetate yields the tri~uoromethyl ester plus the acid ~uoride in 00) yield ð81JOC3638Ł and low yields were also obtained after electro~uorination of methyl esters ð89JFC"49#062Ł\ whereas photochlorination of methyl perchloro!2!butenoate at RT gave the corresponding trichloromethyl ester in more than 82) yield ð58CB2016Ł\ and pho! tochlorination of dimethyl carbonate yields bis"trichloromethyl# carbonate in quantitative yield ð72HOU"E3#0257Ł[ Trichloromethyl esters are\ furthermore\ formed by the reaction between an alcohol and diphosgene "CCl2C"1O#Cl# in 51Ð64) yield ð29JPR109\ 29JPR70Ł and obtained in 71Ð80) yield by photochlorination of methyl chloroformate ð79OS"48#084Ł[ Bis"tri~uoromethyl# oxalate has been obtained in 80) yield by irradiation of a mixture of "CF2#1O1 and CO with a low! pressure Hg!lamp ð56MI 596!91\ 57MI 596!90Ł[ Other methods include thermal decomposition of methyl"tri~uoromethyl#dioxirane which yields tri~uoromethyl acetate "Equation "49## ð80JA6543Ł
120
Three Halo`ens
and cleavage of amides with CF2OF at RT which gives N\N!dihaloamines and tri~uoromethyl esters "Scheme 09# ð63JCS"P0#621\ 79JFC"04#190Ł[ O F3C
∆
MeCO2CF3 + F3CCO2Me
O
(50)
R O
R N
F3COF (excess)
R
F3COCR2CR2NF2 +
R R = H, Me
O2N
CO2CF3
NO2 O R1
N H
O
F3COF
R2
R1
+ F2NR2 OCF3
Scheme 10
"iv# Trihalomethyl hypohalites\ CHal02OHal 1 The ~uorinating agent tri~uoromethyl hypo~uorite may be prepared in good yields from CO ð37JA2875Ł\ CO1 ð55IS054Ł and COF1 ð58JA3321Ł by treatment with elemental ~uorine in the presence of silver"II# ~uoride[ The hypo~uorite is quite thermostable and does not eliminate ~uorine unless heated above 164>C[ Tri~uoromethyl hypochlorite is prepared in 88) yield from carbonyl ~uoride by treatment with chlorine mono~uoride:cesium ~uoride ð58JA1891Ł[
"v# O!Trihalomethyl peroxides\ CHal2OOR and trihalomethyl sulfonates\ CHal2OSO1R Tri~uoromethyl hydroperoxide "CF2OOH# is prepared in 79) yield by hydrolysis of CF2OOCOF ð60JA2771Ł or by thermal decomposition of 0!hydroxy!1\1\1!tri~uoro!0!"tri~uoromethyl#ethyl hydroperoxide "0#\ which is prepared by oxidation of hexa~uoroacetone with 89) H1O1 ð60CC673Ł[ Bis"tri~uoromethyl# peroxide is prepared in 81) yield from carbonyl ~uoride and chlorine tri~uoride "4 h at 149>C# ð54USP2191607Ł or tri~uoromethyl hypo~uorite ð46JA4517Ł[ Chloro tri! ~uoromethyl peroxide adds to alkenes "−000>C:RT\ 1:26 h "depending on the alkene type## in analogy with tri~uoromethyl hypochlorite^ b!chloroalkyl tri~uoromethyl peroxides are formed "09Ð 64) yield# "Equation "40## ð64JA02Ł[ F3C F3C
O OH OH (1)
R1
R3
–111 °C
F3COOCl + R2
R1 F3COO R2 34–75%
R4
R3 Cl R4
(51)
Trichloromethyl hydroperoxide has also been prepared by photoperoxidation of trichloromethane at RT "Equation "41## ð74AG37Ł[ O2, hν
CHCl3 20 °C
Cl3COOH
(52)
Acylation of tri~uoromethyl hydroperoxide is achieved by treatment with an acyl ~uoride under dry conditions[ Tri~uoroacetyl tri~uoromethyl peroxide has been prepared in this way "07 h\
121
Four Halo`ens or Three Halo`ens and One Other Heteroatom
RT# in 84) yield ð60JA2771Ł[ Acetyl trichloromethyl peroxide has been prepared similarly from trichloromethyl hydroperoxide and acetyl chloride ð74AG37Ł[ Tri~uoromethyl tri~uoromethanesulfonate may be prepared from the silver"I# sulfonate and tri~uoroiodomethane "199>C\ 13 h# in 75) yield ð68TL2754Ł or from tri~uoromethanesulfonyl hypochlorite and tri~uorobromomethane "−000>C\ 0 h# in 84) yield ð79JA1570Ł[ Trichloromethyl tri~uoromethanesulfonate has been prepared from mercury"II# tri~uoromethanesulfonate and bromotrichloromethane "9>C\ 01 h# in 67) yield ð58CB1049Ł[
"vi# N!Trihalomethoxy compounds\ CHal2ON"1O#nR A general review of the synthesis of O!alkylated hydroxylamines has recently been given by Andree and Kluth ð89HOU"E05a#103\ 89HOU"E05a#160Ł[ O!"Tri~uoromethyl#di~uoroformaldehyde oxime has been prepared in excellent yield by de! hydro~uorination of CF2ONHCF2 with KF[ It is thermally stable at RT but dimerizes at RT in the presence of CsF to CF2N"OCF2#CF1NOCF2 ð70JFC"07#330Ł[ Treatment of trichloromethyl hydroperoxide with N1O4:NaHCO2 at −14>C leads to trichloro! methyl pernitrate "CCl2COONO1# ð74AG37Ł[
"vii# Metal trihalomethoxides\ CHal2OM Potassium tri~uoromethoxide may be prepared from carbonyl ~uoride and potassium ~uoride in acetonitrile at 19>C[ This salt is more stable than the corresponding alcohol and can be heated in solution to 79>C without formation of carbonyl ~uoride ð54CJC0782Ł[
5[96[1[0[1 Three halogens and a sulfur function "i# Trihalomethanethiols\ CHal2SH Tri~uoromethanethiol is a stable compound whereas the other trihalomethanethiols may be expected to be rather unstable ð72HOU"E3#514\ 82TL1862Ł[ The former has been prepared from mer! cury"II# tri~uoromethanethiolate in 88) yield by treatment with hydrogen chloride ð42JCS2108Ł or in 89) yield by treating "tri~uoromethylthio#silane with hydrogen iodide ð59JCS2405Ł[ The synthesis of trichloromethanethiol has previously been claimed by Connolly and Dyson ð23JCS711Ł\ but a recent investigation showed this to be in error ð82TL1862Ł[
"ii# Trihalomethyl sul_des\ CHal2SR The synthesis of sul_des has previously been reviewed by Gundermann and Humke ð74HOU"E00#047Ł[ Photochlorination of aryl methyl sul_des leads to aryl trichloromethyl sul_des which may be transformed to the corresponding tri~uoromethyl analogues by treatment with SbF2 ð26FRP719684\ 27BRP368663\ 41ZOB1105\ 43JGU774\ 59JOC59Ł[ In the presence of electron!withdrawing groups in the aromatic moiety BF2 catalysis and higher reaction temperatures are required for the ~uorination step ð64S610Ł[ Aryl tri~uoromethyl sul_des have\ furthermore\ been prepared from the corresponding aryl halides by direct tri~uoromethylthiolation with methyl ~uorosulfonyldi~uoroacetate "FSO1CF1! CO1Me#\ CuI and S7[ The choice of solvent and of aryl halide as well as of the metal iodide is of great importance[ Yields ranging from 30) to 63) have been reported in HMPA and N! methylpyrrolidone whereas no reaction is observed in DMF[ Aryl iodides were found to be most reactive and aryl chlorides inactive ð82CC807Ł[ Replacement of CuI by KI results in the formation of tri~uoromethane after work!up ð78CC694Ł[ Replacement of aryl bound halogen by a tri~uoromethylthio group can also be accomplished with di}erent soft metal tri~uoromethanethiolates\ CF2SM\ M being Cu"I#\ Ag"I# or Hg"II#[ Thus\ CF2SCu "74Ð029>C\ 0[4Ð5 h in DMF\ HMPA or N!methylpyrrolidone#\ tri~uoro! methanethiolates aryl iodides in yields of approximately 64) ð74S556Ł[ This method is also
122
Three Halo`ens
available for the synthesis of tri~uoromethylthio substituted heteroaromatics\ and the best yields are achieved with electron!poor systems ð64S610Ł[ Yields may\ furthermore\ be improved by use of copper"I# tri~uoromethanethiolate on alumina support ð89JFC"37#138Ł[ Mercury"II# bis"tri~uoromethanethiolate#\ "CF2S#1Hg\ reacts with alkyl and allyl chlorides with formation of the corresponding tri~uoromethyl sul_des ð48JA2464\ 56JOC1952\ 70TL2936Ł[ Silver"I# tri~uoromethanethiolate\ CF2SAg\ reacts with alkyl halides under formation of alkyl tri~uoromethyl sul_des with an insoluble silver halide as a convenient by!product ð50JCS1486\ 54ZOB0517Ł[ Other sources of tri~uoromethanethiolate ions which have been used in nucleophilic aromatic substitution include the in situ formation of tri~uoromethanethiolate from thiocarbonyl ~uoride or bis"tri~uoromethyl# trithiocarbonate ""CF2S#1C1S# and calcium\ potassium or caesium ~uoride ð41JCS1087\ 74C074\ 76JCS"P0#1008\ 77JCS"P0#0068Ł[ Electron!rich aromatic systems undergo substitution with tri~uoromethanesulfenyl chloride ð49JA2418\ 42CB446\ 53JOC787\ 66CB56\ 67JFC"00#498Ł and trichloromethanesulfenyl chloride ð52ACS1469Ł\ in some cases under free radical conditions\ yielding aryl tri~uoromethyl sul_des in good yields "generally in excess of 59)# and aryl trichloromethyl sul_des\ respectively[ Tri~uoromethanesulfenyl chloride as well as tri~uoromethanesulfenyl ~uoride reacts with nucleophiles^ with alkenes they form b!halo"tri~uoromethylthio#alkanes ð51JA2037\ 56JOC1952\ 76JFC"23#364Ł\ and with aryl Grignard reagents\ tri~uoromethanesulfenyl chloride "at 9>C# forms aryl tri~uoromethyl sul_des\ which are\ however\ contaminated with the corresponding aryl chlorides ð53JOC784Ł[ Tri~uoromethanethiol also reacts with alkenes under UV irradiation with formation of the corresponding alkyl tri! ~uoromethyl sul_des ð50JA739Ł[ Aromatic potassium thiolates react with bromotri~uoromethane under pressure "1Ð2 atm\ RT\ DMF# to give the corresponding tri~uoromethyl sul_des "6Ð64) yield# ð73CC682\ 74JOC3936Ł[ The use of mixed tetrahalomethanes such as dibromodi~uoromethane or bromochlorodi~uoromethane leads to mixed halomethyl sul_des ð70TL0886\ 70TL212Ł[ Alkylation of aliphatic and aromatic disul_des may be conducted in DMF:H1O at RT under radical conditions by treatment of bromotri~uoromethane with sulfur dioxide radical anion "derived from Na1S1O3:NaO1SCH1OH# and Na1HPO3 to neutralize the sulfur dioxide formed during the reaction "20Ð82) yield# ð80CC882Ł[ Tri~uoroiodomethane reacts similarly with sul_des under UV irradiation\ but more slowly\ for example\ the reaction with dimethyl sul_de "hn\ 10 days# gives a 81) yield of tri~uoromethyl methyl sul_de ð61JCS"P0#1079Ł[ This reaction has been extended to alkane!\ arene! and heteroarenethiols as well ð68ZOR285\ 68ZOR0134Ł and may\ furthermore\ be conducted under phase transfer conditions "41Ð74) yield# ð71JFC"10#254Ł[ N!"Tri~uoromethyl#!N!nitrosobenzenesulfonamide "CF2N"NO#SO1Ph\ TNS!B#\ N!"tri~uoro! methyl#!N!nitrosotri~uoromethanesulfonamide "CF2N"NO#SO1CF2\ TNS!Tf#\ S!"tri~uoromethyl#! dibenzothiophenium tri~ate "TBT!Tf# and its seleno analogue "TBSe!Tf# "1#\ and "3!chlorophenyl#! "1\5!dimethylphenyl#tri~uoromethylsulfonium hexa~uoroantimonate "2# have been developed as e.cient tri~uoromethylating agents and are more easily handled than tri~uoroiodomethane gas[ Thus\ TNS!B reacts with dialkyl sul_des to give the corresponding tri~uoromethyl alkyl sul_des in 44Ð53) yield ð71TL2818Ł[ TNS!Tf gives generally higher yields of tri~uoromethyl sul_des from thiols and dialkyl sul_des after shorter reaction times ð75BCJ336Ł[ The reaction of sodium alkane! thiolates with "1# ð89TL2468Ł produces the corresponding tri~uoromethyl sul_des in 36Ð76) yield\ as does treatment with "2# ð73ZOR004Ł[
Cl Z+ CF3
+
TfO–
S
Z = S, Se, Te
SbF6– CF3
(2)
(3)
Direct chlorination of methyl sul_des leads to trichloromethyl sul_des in yields ranging from 45Ð099)\ as does chlorination of alkyl halodithioformates a reaction which also may be used for the formation of dichlorohalomethyl sul_des ð28AG346\ 48ZOB2675\ 59ACS1129\ 51ACS006Ł[ Trichloromethyl sul_des have\ furthermore\ been prepared in 59Ð65) yield from thiocyanates by treatment with trichloromethyl anions "derived from CHCl2:NaOH# under phase transfer conditions ð63S163Ł[ Finally\ trihalomethyl sul_des can be interconverted] CF2SR:CCl2SR "with AlCl2#^ CF2SR:
123
Four Halo`ens or Three Halo`ens and One Other Heteroatom
CBr2SR "with BBr2 or AlBr2#^ CCl2SR:CF2SR "with KF:07!crown!5\ SbF2 or HF#^ CCl2SR: CBr2SR "with HBr#[ Other ~uorinating agents include AgBF3\ Hg1F1 and ðBnNMe2Ł¦F− ð27USP1097595\ 41JA2483\ 45CB0059\ 56ZOB0669\ 60GEP1992032\ 66JOC1913\ 70TL0886Ł[ Kolomeitsev et al[ have developed a method for the synthesis of tri~uoromethyl sul_des from the corresponding alcohols[ The alcohol is treated with bis"diethylamino# chloro phosphite which gives the intermediate diethylamino alkyl phosphite "ROP"NEt1#1# in 79Ð89) yield[ Further treatment with bis"tri~uoromethyl# disul_de gives the tri~uoromethyl alkyl sul_de in 89Ð84) yield[ The overall yields in this two step procedure are excellent "61Ð75)# ð83S034Ł[ Table 4 presents a summary of selected methods for the formation of trihalomethyl sul_des[ Table 4 Selected methods for the formation of trihalomethyl sul_des[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Startin` material Rea`ent"s# Reaction Product Ref[ conditions "yield# ")# ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * Ar0SCCl2 "45Ð099# "see text# Ar0SMe Cl1\ hn R0SC"1S#X R aryl or alkyl X Cl\ F
Cl1
½39>C\
R0SCCl2 "04Ð79#
48ZOB2675
Ar0X\ X Br or I Ar Ph or heteroaromatics
FSO1CF1CO1Me\ S7\ CuI
099Ð019>C\ 4Ð7 h
Ar0SCF2 "30Ð63#
82CC807\ 78CC694
Ar0I\ Ar Ph or pyridine
CF2YCu Y S\ Se
74Ð029>C\ 4Ð5 h
Ar0SCF2 "30Ð84#
89JFC"37#138\ 74S556\ 64S610
ArH\ ArH elec[ rich aromatics
CF2SCl\ Lewis cat[
59>C\ 19 h
Ar0SCF2 "39Ð67#
"see text#
R1C1CR1
CF2SCl\ hn
CF2S0CR1CR10Cl "40Ð72#
56JOC1952\ 51JA2037
Ar0MgX
CF2SCl
R1C1CR1
CF2SH\ hn
Ar0SK
CF2Br
R0SNa
9>C
Ar0SCF2 "½49)#
53JOC784
CF2S0CR1CR10H "45Ð71#
50JA739
Ar0SCF2 "6Ð64#
74JOC3936\ 73CC682
"1# or "2#
R0SCF2 "36Ð76#
89TL2468\ 73ZOR004
R1S
TNS!B or TNS!Tfa
R0SCF2 "44Ð53#
75BCJ336\ 71TL2818
R1S\ R aryl or alkyl
CF2Br\ Na1S1O3\ NaO1SCH1OH\ Na1HPO3
R0SCF2
80CC882
Ph0SCCl2
SbF2\ "BF2#
Ph0SCF2 "69#
"see text#
R0SCX2\ X F\ Cl\ Br
"see text#
R0SCY2 Y F\ Cl\ Br
"see text#
1Ð2 atm\ RT\ 2 h
RT
i\ −39>C\ 1 h^ R0SCF2 83S034 R0OH\ R alkyl i\ "Et1N#1PCl:NEt2^ or benzyl ii\ CF2SSCF2 ii\ −49Ð19>C\ 4 min[ ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * a N!"Tri~uoromethyl#!N!nitrosobenzenesulfonamide "CF2N"NO#SO1Ph\ TNS!B#\ N!"tri~uoromethyl#!N!nitrosotri~uoromethanesulfon! amide "CF2N"NO#SO1CF2\ TNS!Tf#[
"iii# Trihalomethyl sulfoxides and trihalomethyl sulfones\ CHal2S"1O#nR The synthesis of sulfoxides and sulfones has previously been reviewed by Gundermann and Humke ð74HOU"E00#554Ł and by Schank ð74HOU"E00#0018Ł[ Partial oxidation of alkyl:aryl tri~uoromethyl sul_des with 16) hydrogen peroxide in acetic acid "1 h re~ux# yields the corresponding sulfoxides ð54ZOB0517Ł[ More drastic oxidation with nitric acid\ hydrogen peroxide or chromium trioxide in glacial acetic acid gives the corresponding sulfones ð41JA2483\ 54ZOB0517\ 56JOC1952\ 76JCS"P0#1008\ 82CC807Ł[ The transfer of CX2SO1 groups is possible by reactions of nucleophiles such as BuLi with electrophilic species like "CF2SO1#1O\ "CF2SO1#1NPh and CF2SO1Cl[ In the case of primary or
124
Three Halo`ens
secondary organometallics ditri~ation is possible due to the presence of acidic a!protons in the monotri~ated products ð66JOC2764Ł[ Alkynyl tri~uoromethyl sulfones have been prepared from sodium alkynides and tri~ic anhydride in 06Ð64) yield ð81T078Ł[ Monotri~ation of aromatic compounds can be carried out as FriedelÐCrafts tri~ation with "CF2SO1#1O:AlCl2\ but only aromatic compounds of at least intermediate reactivity such as xylene\ toluene\ and benzene are tri~ated ð66JOC2764Ł[ Aryl tri~uoromethyl sulfones have been prepared in high yields "69Ð88)# by di~uorocarbene insertion into arenesulfonyl ~uorides[ The reagent mixture used is Me2SiCF2 or Me2SnCF2 and "Me1N#2S¦Me2SiF1−"TASF#[ The yield is una}ected by electronic e}ects of arene substituents "Equation "42## ð89S0040Ł[ ArSO2F
2Me3MCF3, TASF
ArSO2CF2F 70–99% TASF = (Me2N)3S+ Me3SiF2– M = Sn, Si
(53)
THF, 20 °C
Transformation of an arenesulfonamide into an N!"tri~uoromethyl#azosulfonylarene is e}ected by treatment of the amide with tri~uoronitrosomethane in base "70Ð81) yield#[ This intermediate eliminates N1 on heating to form the corresponding tri~uoromethyl phenyl sulfone "½39) yield# "Scheme 00# ð71CL0408Ł[ F3CNO + H2NSO2Ar
base
∆
F3CN=NSO2Ar
F3CSO2Ar –N2
81–92% Scheme 11
~40%
"iv# S!Trihalomethyl thio! and dithioesters\ CHal2SC"1Z#R "Z O or S# Tri~uoromethyl thioesters have been prepared by the reaction of mercury"II# bis"tri~uoro! methanethiolate#\ "CF2S#1Hg\ with acyl chlorides "39Ð49>C\ 12Ð40) yield# ð48JA2464Ł[ Bis"tri! ~uoromethyl# trithiocarbonate is formed in ½099) yield by CsF treatment at 9>C of thiocarbonyl di~uoride ð55AG895\ 57CB1598Ł[ FriedelÐCrafts "tri~uoromethyl#thiothioacylations have been achieved with HF:SbF4 and FC"1S#SCF2 ð76CB318Ł with the latter formed from thiocarbonyl ~uoride and potassium ~uoride ð57CB1598Ł "Scheme 01#[ The corresponding "trichloromethyl#thiothioacylation "69>C\ 3 h^ RT 05 h# has been achieved in 15) yield by treating anthracene with trichloromethyl chlorodithioformate formed in 64) yield from trichloromethanesulfenyl chloride and CS ð73JOC2743Ł[ Condensation of bis"tri~uoromethyl# trithiocarbonate ""CF2S#1C1S# with "CF2S#1C1C"SCF2#1 in the presence of a catalytic amount of HgCl1 "2 d at 069>C# gives 0\0!bis"tri~uoromethylthio#!1\1!bisð"tri~uoro! methylthio#thiocarbonylŁethene in 09) yield\ with bis"tri~uoromethyl# disul_de as the main product ð66CB805Ł[
S
S F M=K M = Cs
+ F
F 3 1
1 1
S
(SCF2)x +
+ MF
–20–0 °C, 1 h –78 °C, 18 h
10–15%
F3CS
SCF3 58%
100% R
S
S HF/SbF5 +
SCF3 F
SCF3
SCF3
Et2O –50 °C–RT
Scheme 12
R
R Yield (%) H 65 4-MeO 54 3-CF3 27 2,5-F2 35
125
Four Halo`ens or Three Halo`ens and One Other Heteroatom
"v# Trihalomethanesulfenyl\ !sul_nyl and !sulfonyl halides^ CHal 02S"1O#n"Hal 1# The synthesis of sulfenyl\ sul_nyl and sulfonyl halides has previously been reviewed by Schubart ð74HOU"E00#52Ł\ Krauthausen ð74HOU"E00#503Ł and Pawlenko ð74HOU"E00#0956Ł[ See also the review by Sizov et al[ on the formation of poly~uoroalkanesulfenyl chlorides ð81RCR406Ł[ In this section only sulfenyl halides are treated\ due to their synthetic importance in the synthesis of trihalomethyl sul_des[ Umpolun` of metal trihalomethanethiolates can be achieved by chlorination to the corresponding trihalomethanesulfenyl chlorides ð50JCS1486Ł[ Bromine and iodine\ however\ oxidize silver"I# tri! ~uoromethanethiolate to bis"tri~uoromethyl# disul_de ð50JCS1486Ł[ The industrial preparation of trichloromethanesulfenyl chloride takes place by chlorination of carbon disul_de under conditions which suppress the formation of bis"trichloromethyl# disul_de ð60S367\ 55FRP0326897Ł[ A general method for the synthesis of trihalomethanesulfenyl halides is to halogenate "Hal1# thiocarbonyl halides and this method can therefore also be used to prepare mixed tri! halomethanesulfenyl halides ð48ZOB2681\ 51JCS3250\ 53AG796\ 65CB2321Ł^ furthermore\ by halogen exchange in trihalomethanesulfenyl halides with SbF2:SbCl4 "Br:F#\ HF "Cl:F#\ NaF "Cl:F#\ HF:CrOF "Cl:F# or HBr "Cl:Br# ð47USP1710443\ 48ZOB2390\ 48ZOB2673\ 59JOC1905\ 56GEP0121843Ł[ Still other methods include chlorination of disul_des\ for example chlorination of dimethyl disul_de leads to trichloromethanesulfenyl chloride in 79) yield and high purity while photo! chlorination at RT of bis"tri~uoromethyl# disul_de leads to tri~uoromethanesulfenyl chloride in 44) yield ð42JCS2108\ 50USP2903960Ł[
"vi# Trihalomethanesulfenic\ !sul_nic and !sulfonic derivatives^ CHal2S"1O#nZR The trihalomethanesulfenyl\ !sul_nyl\ and !sulfonyl halides are important starting materials for the synthesis of other trihalomethanesulfenyl\ !sul_nyl\ and sulfonyl derivatives[ For example mercury"II# bis"tri~uoromethanethiolate# ð"CF2S#1HgŁ\ reacts with sulfenyl chlorides with formation of the corresponding tri~uoromethyl disul_des ð48JA2464Ł[ Other methods which allow the formation of mixed trihalomethyl disul_des are the photoreaction between thiocarbonyl halides and trihalo! methanesulfenyl halides ð57CB1506Ł and the photoreductive dimerization of trihalomethanesulfenyl chlorides with\ for example\ CO as reductant ð56JINC1708Ł[ Trihalomethanesulfenic acids are\ as most other sulfenic acids\ unstable[ Trichloro! methanesulfenic acid for instance eliminates HCl with formation of dichlorosul_ne "Cl1C1S1O# ð58CC767Ł\ whereas the sul_nic and sulfonic acids are stable compounds[ A preparative method which gives access to halodi~uoromethanesulfonic acid derivatives in high yields is the decarbonylative photolysis of HalC"1O#CF1SO1F "the reaction is conducted at 79Ð89>C for Hal Cl\ 49>C for Hal Br\ RT for Hal I# ð68S861Ł[ The synthesis of sulfenic\ sul_nic and sulfonic acid derivatives has been reviewed previously by Schubart ð74HOU"E00#52Ł\ Krauthausen ð74HOU503Ł\ Pawlenko ð74HOU"E00#0944\ 74HOU"E00#0973Ł and Jager ð74HOU"E00#0962Ł and is not discussed here[ See\ however\ the review by Sizov et al[ on transformation of poly~uoroalkanesulfenyl chlorides ð81RCR406Ł[ The CF2SO1 group "in CF2SO1Ar# was found by NMR measurements to be even more electron! attracting than the NMe2 group "in ArNMe2¦# ð57ZOB1480Ł[
"vii# Metal trihalomethanethiolates^ CHal2SM Metal trihalomethanethiolates are important as precursors of aryl trihalomethyl sul_des "vide supra# and their synthesis is therefore mentioned here[ Copper"I# tri~uoromethanethiolate\ CF2SCu\ is obtained in nearly quantitative yield by heating "49Ð59>C# CF2SSCF2 with copper powder in DMF\ HMPA or N!methylpyrrolidone for 0Ð2 h\ depending on the activity of the copper powder ð74S556Ł[ The thiolate can be used in situ\ but also isolated and stored until needed[ The copper"I# thiolate can also be prepared by reaction of mercury"II# bis"tri~uoromethanethiolate# with copper powder ð48JA2464Ł or by reaction of AgSCF2 with Cu:CuBr ð74S556Ł[ Mercury"II# bis"tri~uoromethanethiolate#\ "CF2S#1Hg\ may be prepared from HgF1 and carbon disul_de in 61) yield after heating 3 h at 149>C in a steel autoclave ð48JA2464Ł or photochemically in 89) yield from bis"tri~uoromethyl# disul_de and metallic mercury ð42JCS2108Ł[
126
Three Halo`ens
Silver"I# tri~uoromethanethiolate\ CF2SAg\ is formed in 68) yield by the reaction of dry silver"I# ~uoride with dry carbon disul_de after heating 01 h at 039>C in a steel autoclave ð50JCS1486Ł^ it reacts with alkyl halides with formation of alkyl tri~uoromethyl sul_des and an insoluble silver halide as a convenient by!product ð50JCS1486\ 54ZOB0517Ł[
5[96[1[0[2 Three halogens and a Se or Te function "i# Tri~uoromethylselenium compounds^ CF2SeR The chemistry of tri~uoromethylselenium compounds has been reviewed and compared with that of the corresponding sulfur compounds ð75JFC"21#304Ł[ Aryl tri~uoromethyl selenides can be prepared from aryl halides and "CF2#SeCu in analogy with the synthesis of the corresponding tri~uoromethyl sul_des "Equation "43## ð74S556Ł[ Se!"Tri! ~uoromethyl#dibenzoselenophenium tri~uoromethanesulfonate "1^ Z Se# can be obtained by ~uo! rination of a mixture of 1!ð"tri~uoromethyl#selenoŁbiphenyl with CF2SO2H and by treatment of the corresponding sulfoxide with "CF2SO1#1O[ Compound "1# can be used as an electrophilic tri~uoromethylation reagent "vide supra# ð82JA1045Ł[ Bis"tri~uoromethylseleno#ketene is available by dehydration of bis"tri~uoromethylseleno#acetic acid or by dehydrochlorination of the corresponding acid chloride ð81CB460Ł[ Z X
I
+ F3CYCu
85–130 °C 1.5–6 h
Z
YCF3
X
+ CuI
(54)
41–95%
X = H, Me, NO2; Y = S, Se; Z = CH, N
Mercury"II# tri~uoromethaneselenolate reacts with S!tri~uoromethyl bromothioformate ð"CF2#SC"1O#BrŁ "029>C for 05 h# with formation of "CF2S#C"1O#Se"CF2# ð67CB1780Ł[ Run overnight at 9>C the same reaction gives a yield of 75) ð65CB2321Ł[ Oxidation of an aryl tri~uoromethyl selenide with chlorine yields the corresponding aryl! dichloro"tri~uoromethyl#selenane\ ArSeCl1"CF2# ð74S556Ł[ Aryl tri~uoromethyl selenides can be oxidized with chlorine:water to the corresponding selenoxides and with tri~uoroperacetic acid to the corresponding selenones ð57ZOB1498Ł[ Tri~uoromethaneselenonic acid\ CF2SeO2H was prepared for the _rst time by Haas and Weiler in 0874 by oxidation of CF2SeO1H with KMnO3 under neutral aqueous conditions[ Upon attempted puri_cation it decomposes "at concentrations higher than 89)# to CF3\ COF1\ SeO1 and H1O ð74CB832Ł[
"ii# Tri~uoromethyltellurium compounds^ CF2TeR Mixtures of bis"tri~uoromethyl# telluride and dialkyl tellurides are subject to ligand exchange and form alkyl tri~uoromethyl tellurides such as BnTe"CF2# and ButTe"CF2# ð81C67\ 81OM1836Ł[ Mixtures of "CF2#1Te and "C5F4#1Te as well as of "CF2#1Te1 and "C5F4#1Te1 undergo scrambling under irradiation to give "CF2#Te"C5F4# and "CF2#TeTe"C5F4#\ respectively ð89JFC"37#196\ 82CM0210Ł[ An 75) yield of dimethyl"tri~uoromethyl#telluronium iodide is obtained in the photoreaction "at −67>C# of Me1Te and CF2I ð78ZAAC"465#114Ł[ Te!"Tri~uoromethyl#dibenzotellurophenium tri~uoromethanesulfonate "1^ Z Te# can be obtained by treatment of 1!ð"tri~uoromethyl# telluroŁbiphenyl with "CF2SO1#1O and DMSO[ Compound "1# can be used as an electrophilic tri~uoromethylation reagent ð82JA1045Ł[ Tetrakis"tri~uoromethyl#tellurane "CF2#3Te\ which has been obtained from dichlorobis"tri~uoromethyl#tellurane and "CF2#1Cd\ reacts with ~uoride ions to form ð"CF2#3TeFŁ−\ with ~uoride ion acceptors to form ð"CF2#2TeŁ¦\ and with XeF1 to form the hypervalent tellurium compound "CF2#3TeF1 ð81ZAAC"597#58Ł[
5[96[1[1 Three Halogens and a Group 04 Element 5[96[1[1[0 Three halogens and a nitrogen function This subject has previously been reviewed by Marhold ð72HOU"E3#514Ł[
127
Four Halo`ens or Three Halo`ens and One Other Heteroatom
"i# Trihalomethylamines\ CHal2NR1 The unsubstituted and monosubstituted trihalomethylamines possess more or less salt character and are quite unstable[ The phosgeneiminium character makes them prone to hydrolysis "Equation "44##[ X
X
X
NH2+ X–
NH2 X
(55)
X
"a# Primary trihalomethylamines\ CHal2NH1[ Tri~uoromethylamine has been prepared by treat! ing N\N!dichloro!N!"tri~uoromethyl#amine with HCl at −67>C which gives the hydrochloride[ The free base is stable below ½−29>C\ above which it eliminates HF with formation of di~uoro! phosgeneimine "Scheme 02# ð68JA236Ł[ Synthesis of trichloromethylamine is achieved by treating ClCN with HCl[ The intermediate hydrochloride is unstable\ but addition of antimony"V# chloride converts it into the stable hexachloroantimonate salt ð53CB0175\ 62BSB12Ł[ –Cl2
F3CNCl2 + 3HCl
F3CNH3+ Cl– Scheme 13
amine base
F3CNH2
"b# Secondary trihalomethylamines\ CHal2NHR[ Secondary tri~uoromethylamines have been prepared from N!substituted isocyanide dichlorides "CCl11NR# by reaction with HF[ Yields of 58Ð87) have been achieved with N!aryl substituted compounds\ whereas the aliphatic counterparts dimerize and:or polymerize "Equation "45## ð52BEP521254Ł[ Bis"tri~uoromethyl#amine may be syn! thesized by addition of HF to tri~uoromethyl isocyanide di~uoride "CF2N1CF1# in 78) yield ð48ZOB1048Ł or by HF treatment of trichloromethyl isocyanide dichloride in 34) yield ð44JCS1421\ 47JA2593Ł[ Cl
R N
HF
Cl R = aryl
F3CNHR
(56)
69–98%
"c# Tertiary trihalomethylamines\ CHal2NR1[ Tertiary tri~uoromethylamines are stable com! pounds which have been prepared by ~uorination of R1NC"1S#SSC"1S#NR1 with either SF3 or COF1\ or by ~uorination of N\N!disubstituted ~uorothioformamides "FC"1S#NR1# with SF3[ These methods may be applied to both aryl and alkyl tri~uoromethylamines "Equation "46## ð50JA2311\ 51JA3164\ 60ZOR1999Ł[ S R2N
S
S
NR2 S
SF4
R2NCF3 58–73%
(57)
Tertiary trichloromethylamines have been made similarly by chlorination of N\N!disubstituted chlorothioformamides with Cl1 or PCl4 "½65) yield# ð48ZOB2675\ 60ZOR1973Ł\ by chlorination of R1NC"1S#SC"1S#NR1 with COCl1 "82) for R Me# ð72HOU"E3#514Ł\ by chlorination of N\N! diarylthioformamides "HC"1S#NAr1# and of alkanesulfonylthioformamides "RSO1C"1S#NR1# ð71GEP2933105\ 61CB1743Ł[ N!"1\3\5!Trichlorophenyl#!N\N!bis"trichloromethyl#amine has been pre! pared by chlorination at 039>C of the corresponding N\N!dimethylamine ð58LA"629#039Ł[ Alkylation of N!substituted phosgeneimines with strong alkylating agents such as RO2SF\ followed by Cl−:FSO2−!anion exchange\ gives the corresponding dichlorophosgeneiminium chlorides ð62AG726Ł[ Dimethyl"tribromomethyl#amine has been prepared similarly to the trichloromethyl and tri~uoromethyl analogues\ for example\ by bromination with Br1 of Me1NC"1S#SS"C1S#NMe1 ð61LA"644#034Ł[ Tertiary tri~uoromethylamines may alternatively be synthesized from the corresponding tri! chloromethylamines by treatment with HF or SbF2 under anhydrous conditions in 47Ð68) yield ð55ZOB0298\ 71GEP2933105Ł[ Bis"tri~uoromethyl#alkylamines are formed by alkylation of metal "K¦\ Cs¦\ Hg1¦# bis"tri! ~uoromethyl#amides in 33Ð73) yield ð79JCS"P0#1143\ 64IZV1168Ł[ N!Bromo! and N!iodo!N\N!bis"tri~uoromethyl#amines add to double bonds with formation
128
Three Halo`ens
of b!bromo! and b!iodoalkyl bis"tri~uoromethyl#amines\ respectively\ in 61Ð87) yield ð47JA2593\ 54JCS5030\ 57JCS"C#685\ 79JCS"P0#0433Ł[ Tris"tri~uoromethyl#amine has been prepared by treatment of tri~uoromethyl isocyanide di! ~uoride with CF2SF4 ð46JA58Ł and as a by!product "11) yield# of the reaction between O\N\N! tris"tri~uoromethyl#hydroxylamine and tri~uoromethyl isocyanide di~uoride where N\N\N?\N?! tetrakis"tri~uoromethyl#hydrazine is the main product ð56JCS"C#0130Ł[ Mixed N\N!dihalo"trihalomethyl#amines "halo equals chlorine or ~uorine# have been prepared in 59Ð64) yield from the corresponding imines by treatment "−19>C for 2Ð3 h# with chlorine mono~uoride ð60IC0524Ł[
"ii# N!Trihalomethylamides\ CHal2NRC"1O#R Isocyanates are used as starting materials for the synthesis of N!alkyl!N!"tri~uoromethyl#! carbamoyl ~uorides and of O!alkyl!N!"tri~uoromethyl#carbamates[ Thus\ tri~uoromethyl iso! cyanate reacts with CsF and subsequently with an alkyl halide\ with formation of N!alkyl!N! "tri~uoromethyl#carbamoyl ~uorides "Scheme 03# ð65IZV198Ł while the reaction of tri~uoromethyl isocyanate with alcohols yields O!alkyl!N!"tri~uoromethyl#carbamates in 55Ð73) yield "Equation "47## ð48ZOB1046Ł[ Aryl isothiocyanates are converted into N!aryl!N!"tri~uoromethyl#carbamoyl ~uorides in 32Ð72) yield by treatment with HgF1\ followed by COF1:CsF "Equation "48## ð54JA3227Ł[ F
F F3CN
•
CsF
O
RBr
O Cs+
–
N
O NCF3
CF3
R
Scheme 14
O F3CN
•
O
+ ROH
F 3C
(58)
OR N H 66–84% F
N
•
S
i, HgF2 ii, COF2/CsF
O
N
CF3 (59) R
R 43–83%
Hydrolysis of ð56JCS"C#1291Ł[
N\N!bis"tri~uoromethyl#carbodiimide
gives
N\N?!bis"tri~uoromethyl#urea
"iii# Trihalomethyl isocyanates\ CHal2N1C1O^ trihalomethyl isocyanide dihalides\ CHal2N1CHal1 and N!"trihalomethyl#carbodiimides CHal2N1C1NR Key starting materials in the synthesis of bis"tri~uoromethyl#amines are\ as mentioned above\ tri~uoromethyl isocyanide di~uoride "CF2N1CF1# and trichloromethyl isocyanide dichloride "CCl2N1CCl1#[ One high yielding method for the synthesis of these is the chlorination of N\N! dimethylcarbamoyl chloride which gives trichloromethyl isocyanide dichloride in 76) yield ð52GEP0111806\ 69GEP0815548Ł^ further treatment with sodium ~uoride yields tri~uoromethyl iso!
139
Four Halo`ens or Three Halo`ens and One Other Heteroatom
cyanide di~uoride which distills o} from the reaction mixture "67) yield\ Scheme 04# ð61CA"66#014841Ł[ Other methods of preparation of these compounds are described in Section 5[19[0[ Me
O
Cl2
Cl3C
N
Cl N
Me
Cl
250–300 °C
Cl
NaF
F3C
F N
150 °C
F
87%
78%
Scheme 15
Other key starting materials in the synthesis of "trihalomethyl#amines are the trihalomethyl isocyanates "CHal2N1C1O#[ Tri~uoromethyl isocyanate is formed in 64) yield from tri! ~uoroacetyl chloride by treatment with azidotrimethylsilane and thermolysis of the intermediary tri~uoroacetyl azide by Curtius amide degradation "Scheme 05# ð68CB1047Ł[ Tri~uoromethyl iso! thiocyanate is formed in 59) yield upon H1S treatment of tri~uoromethyl isocyanide di~uoride\ followed by distillation from NaF ð58ZOB088Ł[ Trichloromethyl isocyanate is unstable and rearranges quantitatively to chloroformyl isocyanide dichloride[ The same product is obtained in 78) yield by photochlorination of methyl isocyanate "Scheme 05# ð65CA"74#031557Ł[ Tribromomethyl isocyanate is formed in 58) yield by NBS bromination of methyl isocyanate "Scheme 05# ð71CB759Ł[ N!"Tri~uoromethyl#carbodiimides are formed in 35Ð79) yield by the reaction between tri! ~uoromethyl isocyanide di~uoride and an alkyl! or arylamine in the presence of KF:Et2N ð79JFC"04#058Ł[ TMS-N3 autoclave
O F3C
MeN
Cl
•
O
20 °C, 2 h hν, Cl2 autoclave
∆, –N2
O F3C
N3
Cl3CN
•
60 °C, 12 h
F3CN
•
O
NBS 16 h
Cl
N Cl
Br Br3CN
•
Cl O
N
Br
O Br
69%
O
O
70 °C, 15 h 89%
MeN
•
75%
O
Scheme 16
"iv# N!Halo"trihalomethyl#amines\ CHal02NRHal1 N!Bromo! and N!iodo!N\N!bis"tri~uoromethyl#amine are to be considered as umpoled amines and thus as key intermediates for the introduction of the bis"tri~uoromethyl#amine functionality by reaction with nucleophiles such as alkenes "vide supra#[ They are formed by bromination and iodination of mercury"II# bis"tri~uoromethyl#amide in 89) and 56) yield\ respectively ð47JA2593\ 55JCS"A#256Ł[ N!Chloro!N\N!bis"tri~uoromethyl#amine is similarly formed in 69) yield by chlori! nation of potassium bis"tri~uoromethyl#amide and N!~uoro!N\N!bis"tri~uoromethyl#amine is obtained by ~uorination of tri~uoromethyl isocyanide di~uoride with elemental ~uorine ð70JFC"06#352Ł[ Addition of halogen to N!halo isocyanide dihalides "Hal1C1NHal# or cyanogen chloride leads to N\N!dihalo!N!"trihalomethyl#amines in 59Ð86) yield ð69CC284\ 61LA"644#034\ 70JFC"06#352Ł[
"v# N!"Trihalomethyl#hydroxylamines\ CHal2NR0OR1^ trihalonitrosomethanes\ CHal2NO and trihalonitromethanes\ CHal2NO1 Photodimerization of tri~uoronitrosomethane\ followed by acid hydrolysis and oxidation with silver oxide\ lead to bis"tri~uoromethyl#aminoxyl radical ð46JCS0630Ł which reacts with alkyl halides with formation of O!alkyl!N\N!bis"tri~uoromethyl#hydroxylamines[ The O!methyl compound was prepared in this way by reaction with iodomethane at RT "Scheme 06# ð58JCS"A#320Ł[ The bis"tri! ~uoromethyl#aminoxyl radical also reacts with activated positions of alkanes with formation of N\N!
130
Three Halo`ens
bis"tri~uoromethyl#hydroxylamine and O!alkyl!N\N!bis"tri~uoromethyl#hydroxylamines "Scheme 07# ð62JCS"P0#0981\ 64JCS"D#1114\ 64JCS"P0#1922\ 79JFC"05#280\ 70JCS"P0#344\ 70JFC"06#220Ł[
F3CNO
F 3C
hν
HCl/H2O
N O NO
F 3C N OH
F 3C
Ag2O
N O•
F3C Scheme 17
F3C
F 3C N OH
F3C
Ag2O
RH
N O•
F 3C
F3C
F3C N OMe
96%
F3C
F3C
F 3C N OR
+
F3C
F3C
MeI
N OH F 3C
9–98% R = CMe2, CH2TMS, CH(Ph)CN, CH2SMe, CH2Ar Scheme 18
N!"Tri~uoromethyl#hydroxylamine "as its diethyl ether adduct# is formed in 37) yield when tri~uoronitrosomethane is treated with potassium hydrogen sul_te in H1O:Et1O\ followed by hydrolysis "Scheme 08# ð71JCS"P0#574Ł[ Tri~uoronitrosomethane reacts as an ene reaction compon! ent\ for instance with propene with formation of N!"tri~uoromethyl#!N!allylhydroxylamine in 89) yield "Equation "59## ð79JCS"P0#0859Ł[ O!Aryl!N\N!bis"tri~uoromethyl#hydroxylamines are prepared in high yield "×79)# from the sodium salt of N\N!bis"tri~uoromethyl#hydroxylamine and an aryl chloride ð70JFC"06#74\ 70JFC"06#480Ł[ O!Benzylated derivatives have been prepared in high yield "×79)# from benzyl chlorides and mercury"II# bisðbis"tri~uoromethyl#aminoxideŁ ð62JCS"P0#0981Ł[
F3CN
O
HO
KHSO3
N SO3– K+
H2O/Et2O –196–20 °C, 2h
HO
H3O+
NH•OEt2
F3C
F3C 48%
Scheme 19
OH F3CN
O
+
F3C
N
(60)
Tri~uoronitrosomethane may be prepared by di}erent methods\ for example by free radical substitution of iodotri~uoromethane with NO:Hg:hn "78) yield# ð43JCS801Ł or by the heating of CF2C"1O#ONO "089>C\ 45) yield# ð51JOC0953Ł or CF2C"1O#NHOH "52) yield# ð59DOK"021#591Ł[ Trichloronitrosomethane has been prepared similarly by the heating of CCl2C"1O#NHOH "89Ð84>C\ 51) yield# ð42JCS1964Ł and by treatment of CCl2SO1Na with HNO2 "45) yield# ð59DOK"021#591Ł[ Nitrotri~uoromethane is available in 38) yield by oxidation of the corresponding nitroso com! pound with Mn1O6 ð42JCS1964Ł[ Trichloronitromethane "chloropicrin# which is commercially avail! able and useful as an insecticide and as a synthetic building block\ can be prepared in a number of ways including the chlorination of nitromethane with strongly alkaline aqueous sodium hypochlorite "89) yield# ð33USP1254870Ł[
"vi# N!"Trihalomethyl#sulfenamides\ CHal2NR0SR1 N\N!Bis"tri~uoromethyl#alkanesulfenamides may be prepared by the reaction of mercury"II# bis"tri~uoromethyl#amide with an alkanesulfenyl chloride[ N\N!Bis"tri~uoromethyl#methane! sulfenamide has been prepared in 85) yield by this method ð55JINC0712Ł[ Another method is the addition of N\N!bis"tri~uoromethyl#!S!"chloro#thiohydroxylamine\ formed by the reaction of N! chloro!N\N!bis"tri~uoromethyl#amine with elemental sulfur ð53USP2010001Ł\ to alkenes which leads to N\N!bis"tri~uoromethyl#!1!chloroalkanesulfenamides "Scheme 19# ð70JFC"08#80Ł[
131
Four Halo`ens or Three Halo`ens and One Other Heteroatom F F3CN F
i, KF ii, Cl2
F 3C N Cl
S 225 °C
F3C
F 3C
N S
N SCl
F 3C 70%
F3C
CClMe2
F3C 81%
Scheme 20
"vii# Metal "trihalomethyl#amides\ CHal2NRM "Trihalomethyl#amines are poor nucleophiles\ but may be converted into stronger nucleophiles by conversion to metal "trihalomethyl#amides[ The starting material for metal "tri~uoromethyl#! amides is tri~uoromethyl isocyanide di~uoride "CF2N1CF1# which by reaction with HgF1 or KF forms the corresponding metal amides ð47JA2593\ 64IZV1168Ł[
"viii# Miscellaneous compounds Tri~uoronitrosomethane reacts with amines with formation of N!tri~uoromethyldiazenes "CF2N1NR# ð50DOK"030#246\ 57ZOB698Ł[ N\N!Bis"dibromomethylene#hydrazine "Br1C1NN1CBr1# reacts with silver"II# ~uoride with formation of N\N!bis"tri~uoromethyl#diazene "CF2N1NCF2# in 81) yield\ which may be further transformed into the corresponding hydrazine "CF2NHNHCF2# by treatment with H1S\ HI or PH2 ð51DOK"031#243\ 51JA1226\ 55JOC2722Ł[
5[96[1[1[1 Three halogens and a phosphorus function Dialkyl! and diarylphosphines react with tetrachloromethane in the presence of triethylamine to yield the corresponding phosphines "CCl2#PR1 in 76Ð84) yield ð80PS"44#074Ł and dichloro! methylenephosphines CCl11PR react with CCl3 in ether in the presence of "Et1N#2P to form bis"trichloromethyl#phosphines "CCl2#1PR in 67Ð70) yield ð81ZOB837Ł[ Tri~uoromethylphos! phaalkenes "CF2#P1CFOR have been prepared from the corresponding di~uoromethylene compounds ð82ZN"B#47Ł[ The iminomethylenephosphine "CF2#P1C1NBut has been prepared from "CF2#P1CF1 and t!butylamine and the cyclic diphosphane "3# is available from "CF2#P1CF1 and 1\2!dimethyl!1\3!butadiene ð80ZN"B#867Ł[ Per~uoro!1!phosphapropene upon addition of an alcohol and subsequent treatment with a secondary amine yields the derivative "CF2#P1C"OR#NR1 "R Me\ Et# in 47) yield ð80HAC274Ł[ P P
CF3 CF3
(4)
Tri~uoromethanephosphonic acid can be obtained by hydrolysis of diiodo"tri~uoromethyl#! phosphine ð43JCS2487Ł[ With alcohols diiodo"tri~uoromethyl#phosphine forms tri~uoromethane! phosphonic acid monoalkyl esters in 17Ð48) yield ð77ZOB0414Ł[ Trimethyl phosphite reacts upon re~ux with tetrachloromethane to form dimethyl trichloromethanephosphonate in 80) yield ð35ZOB0410Ł[ This ester\ when re~uxed with concentrated hydrochloric acid\ is quantitatively converted to trichloromethanephosphonic acid dihydrate ð44JA1758Ł[ Azidobis"tri~uoromethyl#phosphine reacts with "CF2#1P0N1PPh2 to form "CF2#1P0N1P! "CF2#10N1PPh2 ð82JOM"337#108Ł[ Aminobis"trichloromethyl#phosphines such as Me1NP"CCl2#1 can be oxidized with hydrogen peroxide to the corresponding phosphine oxides and with S7 to the corresponding phosphine sul_des[ With chlorine the corresponding chlorophosphonium chlorides are formed which are dealkylated upon heating to MeN1P"CCl2#1[ Aminobis"tri! chloromethyl#phosphines can be cleaved with HCl to form ClP"CCl2#1 ð82ZOB0139Ł[ Dibromo"tri! ~uoromethyl#phosphine "CF2#PBr1 can be converted to the corresponding "tri~uoromethyl#! phosphinylbistriazolide which is useful for the tri~uoromethylphosphonation of carbohydrates ð82TL038Ł[
132
Three Halo`ens 5[96[1[1[2 Three halogens and an As\ Sb\ or Bi function
Mixed di~uorohalomethylarsines are accessible by treatment of arsenic"III# chloride\ bromide or iodide\ respectively\ with di~uorocarbene\ generated from "CF2#1Cd = 1MeCN[ Arsenic"III# ~uoride reacts with the same cadmium reagent with tri~uoromethylation ð89ZAAC"477#15Ł[ Tris"tri~uoro! methyl#stilbine ð89JFC"35#154Ł and tris"tri~uoromethyl#bismuthine ð76JOM"223#212Ł are accessible from the appropriate element halides and "CF2#1Cd[ Diphenyl"tri~uoromethyl#bismuthine and phenylbis"tri~uoromethyl#bismuthine have been prepared from the corresponding phenyl! halobismuthines and "CF2#1Cd ð80JOM"306#C36Ł[ Bis"tri~uoromethyl#chloroarsine yields the cor! responding azide when treated with sodium azide ð81JST"157#278Ł and azidobis"tri~uoromethyl#arsine reacts with triphenylphosphine to give "CF2#1As0N1PPh2 ð82JCS"D#552Ł[
5[96[1[2 Three Halogens and a Metalloid 5[96[1[2[0 Three halogens and a silicon function Compounds with an "a! or b!~uoroalkyl#silane structure are prone to rearrangement with elim! ination of a ~uorosilane R2SiF ð48QR122\ 53AOC"0#032Ł[ The construction of the CF2SiR2 moiety requires several steps such as insertion of di~uorosilylene into the C0I bond of tri~uoroiodomethane\ metathesis of CF2SiFI with SbF2 to yield CF2SiF1\ and subsequent reduction with LAH to tri~uoromethylsilane ð75JOM"205#30Ł^ also bis"tri~uoromethyl#! silane has been prepared ð89JOM"274#196Ł[ A more convenient procedure starts from bromo! tri~uoromethane\ tris"diethylamino#phosphine\ and an appropriate silicon halide ð82OM3829Ł[ Tetra! kis"trichloromethyl#silane has been prepared in 53) yield by photochlorination of "CH1Cl#Me2Si[ The corresponding chlorination of TMS leads to destruction of the reaction mixture ð78ZOB1517Ł[ A reagent prepared from tetrakis"dimethylamino#ethylene and CBr2F reacts with organo! chlorosilanes RnSiCl3−n to give dibromo~uoromethylsilanes "CBr1F#SiRnCl2−n in 16Ð43) yield ð82OM3829Ł[
5[96[1[2[1 Three halogens and a boron function Many tri~uoromethyl boranes are unstable due to the vacant orbital on boron\ which causes halide migration from carbon to boron with formation of di~uorocarbene[ Oxygen or nitrogen"III# ligands as well as tetracoordination of the boron atom increase stability[ Dibutyl"tri~uoromethyl#borane\ "CF2#BBu1\ is formed in the reaction between potassium di! butylborate"I# and tri~uoroiodomethane[ The former reacts with boron tri~uoride to yield di~uo! ro"tri~uoromethyl#borane\ CF2BF1\ ð56JA2335Ł[ Tris"tri~uoromethyl#borane\ "CF2#2B\ is an extremely strong Lewis acid and can only be isolated in the shape of adducts with Lewis bases[ For example\ "CF2#2B = NR0R1R2 can be obtained from "dialkylamino#dichloroboranes "R0R1N#BCl1 and bromotri~uoromethane:tris"diethylamino#phosphine or tri~uoroiodomethane:tetrakis"di! methylamino#ethylene and subsequent alkylation of the secondary amine adducts so formed ð82JOM"335#14Ł[ In dichloromethane solution aminohaloboranes such as Et1NBCl1 and Et1NBBr1 react with CF2Br:P"NEt1#2 to yield the corresponding "CF2#BClNR1\ "CF2#BBrNR1\ and "CF2#1BNR1 ð78JOM"267#014Ł[ Dimethylaminobis"tri~uoromethyl#borane "CF2#1BNMe1 "4# inserts into oxiranes to form the corresponding oxaazoniaboratacyclopentanes "5# ð82ZN"B#824Ł[ Compound "4# also undergoes ene reactions with alkenes ð82JOM"345#08Ł[ With diazoalkanes "4# forms the corresponding three! membered rings "6# ð82AG318Ł[ R
R1 +
+
F3C Me
B N (5)
CF3
Me2N
–
CF3
NMe2
R2
B
F3C Me
O
F3C
B– CF3
R = Me, CH2F, CF3, Et, Bn
R1, R2 = H, Bn, TMS
(6)
(7)
133
Four Halo`ens or Three Halo`ens and One Other Heteroatom
Hexamethyldistannane reacts metathetically with tri~uoroiodomethane to form "tri~uoro! methyl#trimethylstannane[ The latter reacts further with boron tri~uoride to generate ðMe2SnŁ¦ ð"CF2#BF2Ł− which in turn can be converted to the corresponding potassium salt ð59JA4187Ł[
5[96[1[2[2 Three halogens and a germanium function Germanium"II# iodide has been treated with tri~uoroiodomethane in an autoclave at 029Ð024>C and found to give triiodo"tri~uoromethyl#germane\ "CF2#GeI2\ and diiodobis"tri~uoromethyl# germane\ "CF2#1GeI1[ The iodine atoms of the former can be exchanged for chlorine by treatment with silver"I# chloride with formation of "CF2#GeCl2 ð51JA787Ł[ The compounds "CF2#GeF2 and K1ð"CF2#GeF4Ł have been similarly prepared ð59JA5117Ł[ Atomic germanium in a solvent slurry reacts with tetrachloromethane to form "CCl2#GeCl2 and with bromotrichloromethane to form "CCl2#GeBr2 in low yield ð77BCJ2991Ł[
5[96[1[3 Three Halogens and a Metal Function The chemistry of "tri~uoroalkyl#metal compounds has previously been presented in a textbook by Emeleus ðB!58MI 596!91Ł and in reviews by Trichel and Stone ð53AOC"0#032Ł[ The synthetic methods for the preparation of "per~uoroorgano#metallic compounds have been reviewed by Chambers ðB!62MI 596!90Ł\ and tri~uoromethyl!containing transition metal complexes by Morrison ð82AOC"24#100Ł[ Of the di}erent "tri~uoromethyl#metal complexes prepared to date\ donor ð0\1!dimethoxy! ethanel"glyme# or DMFŁ stabilized bis"tri~uoromethyl#cadmium seems to be the most reliable and e.cient tri~uoromethylating agent[ Other "tri~uoromethyl#metal complexes have been prepared\ for which some application in the electronic industry may be found\ such as the stable gold complexes[
"i# Trihalomethyl alkali and earth alkali metals\ CHal2M "M Li\ Na\ K\ Cs\ M`# The preparation of a!haloalkyl Grignard reagents has been reviewed by Villieras ð60MI 596!90Ł[ The trihalomethyl alkali and earth alkali metals are very di.cult to isolate due to the dihalocarbene character of the carbon[ They are therefore most often prepared in situ and used without isolation[ In the case of "trichloromethyl#lithium the position of the equilibrium at −099>C "Equation "50## lies to the side of "trichloromethyl#lithium ð64JA076Ł[ Cl3CLi
:CCl2
+ LiCl
(61)
Ligand exchange has been attempted in the synthesis of "tri~uoromethyl#lithium and !magnesium[ When tri~uoroiodomethane is treated with methyllithium in diethyl ether\ "tri~uoromethyl#lithium is formed initially\ but this complex decomposes into lithium ~uoride and di~uorocarbene which dimerizes[ This is also the case with magnesium ð43JA363\ 53AOC"0#032Ł[ According to Kobrich\ lithiation of 1\1!diphenyl!0!bromoethene with "dichloromethyl#lithium and subsequent treatment with tetrachloromethane gives "trichloromethyl#lithium and 1\1!diphenyl!0\0! dichloroethene[ "Trichloromethyl#lithium has also been prepared in situ from butyllithium and tetrachloromethane or trichloromethane and then treated with a number of electrophiles by Hoeg et al[ ð54JA3036Ł[ "Trichloromethyl#lithium\ !sodium\ !potassium and !caesium have\ furthermore\ been prepared and investigated by IR in an Ar:CCl3 matrix at 04 K ð64JA076Ł[ "Tribromomethyl#lithium should be available by the reaction of butyllithium with tetra! bromomethane[ No data have\ however\ been presented ð56AG04Ł[ "Trichloromethyl#magnesium chloride has been prepared from isopropylmagnesium chloride and CCl3 at −004>C in THF or with CHCl2 at −67>C in THF:hexamethylphosphoric triamide "HMPT# "79:19# in 59) and 69) yield\ respectively[ "Tribromomethyl#magnesium chloride was prepared similarly with CBr3 at −004>C in THF or with CHBr2 at −84>C in THF:HMPT "79:19# in 49) yield ð56BSF0419Ł[
134
Three Halo`ens "ii# Trihalomethylaluminum\ !`allium\ !indium and !thallium\ CHal2MRn\ "M Al\ Ga\ In\ Tl# compounds
Tris"tri~uoromethyl#gallane has been prepared in 25) yield by Guerra et al[ by treating gallium tribromide with a slight excess of Cd"CF2#1 = glyme in CH1Cl1[ Further treatment with tri! methylphosphine or trimethylarsine leads to ð"CF2#2GaPMe2Ł and ð"CF2#2GaAsMe2Ł in quan! titative yields ð89JOM"289#C62Ł[ Naumann et al[ were able to prepare the following tri~uoromethyl group 02 metal complexes ðGa"CF2#1Cl = DMFŁ "in 28) yield#\ ðGa"CF2#2 = DMFŁ "31)#\ ðCd"NCMe#1ŁðGa"CF2#3Ł "38)#\ ðIn"CF2#1Cl = DMFŁ "21)#\ ðIn"CF2#2 = 1NCMeŁ "25)# and ðTl"CF2#2 = 1DMFŁ "34)# from ðCd"CF2#1 = D\ D glyme\ diglyme\ MeCNŁ and GaCl2\ InCl2 or TlCl2[ The reactions were conducted in CH1Cl1\ MeCN or DMF at −29 to 39>C ð80JOM"396#0Ł[ "iii# Trihalomethyltin and !lead\ CHal2MRn "M Sn"II#\ Sn"IV#\ Pb"IV## compounds Tri~uoromethyl"trimethyl#stannane has been prepared in 70) yield by heating at 79>C for 19 h or irradiation of a mixture of tri~uoroiodomethane and hexamethyldistannane "Me2SnSnMe2#[ Chlorination of "tri~uoromethyl#trimethylstannane leads to "tri~uoromethyl#dimethyltin chloride "Scheme 10# ð47JOC0454\ 59JA0777Ł[ SnCl4 + MeMgI
dibutyl ether reflux
SnMe4
SnBr4
Me3SnBr
Na/NH3 (l)
Me3SnSnMe3
120 °C, 3 h
89%
89%
CF3I 80 °C, 20 h
Me3SnSnMe3
Me3SnCF3
Cl2
71%
Me2(CF3)SnCl + MeCl
closed vessel –Me3SnI
Scheme 21
The "tri~uoromethyl#tin halides have been prepared[ Thus\ when tin tetrabromide is heated for 1×04 h at 009>C in an ampoule with Hg"CF2#1\ "CF2#2SnBr "7)#\ "CF2#1SnBr1 "05)#\ and CF2SnBr2 "44)# are formed\ whereas when "CF2#1Cd = diglyme is used as tri~uoromethylating reagent "CF2#3Sn "34)# and CF2SnBr2 "09Ð14)# are collected ð81JOM"322#52Ł[ Tris"tri~uoromethyl#tin iod! ide may be prepared from tetrakis"tri~uoromethyl#stannane^ either by treatment with HI or BrI2 "giving 49Ð79) yield of "CF2#2SnI and 19Ð49) yield of "CF2#1SnI1#[ "Tri~uoromethyl#tin triiodide is formed similarly by HI treatment of tri~uoromethyltin tribromide in 83) yield[ When these products are treated with AgCl for 2 h at 49>C\ the corresponding chlorides are formed in 84) yield[ Tris"tri~uoromethyl#tin ~uoride is formed upon heating "2 h at 099>C# of tetrakis! "tri~uoromethyl#stannane ð81JOM"322#52Ł[ Mixed "tri~uoromethyl#methylstannanes ð"CF2#nSnMe3−nŁ have been prepared by ligand exchange between tetramethylstannane and tetrakis"tri~uoromethyl#stannane ð81JOM"322#52Ł[ Mono!\ bis! and tris"tri~uoromethyl#stannane may be prepared by reduction of "CF2#nSnX3−n with tributylstannane at −49>C for 1 h[ The yields were 78)\ 81) and 34)\ respectively ð81JOM"323#048Ł[ A number of "tri~uoromethyl#lead complexes have been prepared in a stepwise manner by Eujen and Patorra ð81JOM"327#46Ł[ Bis"tri~uoromethyl#cadmium reacts with trimethyl! and triethyllead bromide in sulfolane at 69>C to give "CF2#PbMe2 "40) yield# and "CF2#PbEt2 "45)#[ Bromination "Br1# at 9>C or iodination "I1# at RT gave the corresponding "tri~uoromethyl#dialkyllead halides "alkyl methyl or ethyl# in quantitative yields[ The "tri~uoromethyl#dialkyllead bromides may be transformed into the bis"tri~uoromethyl#dialkyllead complexes ""CF2#1PbMe1 "36) yield# and "CF2#1PbEt1 "49)## by treatment with Cd"CF2#1[ Bis"tri~uoromethyl#methyllead bromide was then prepared in 64) yield\ by bromination at −14>C "61 h# of bis"tri~uoromethyl#dimethyllead\ which by further reaction with Cd"CF2#1 gave tris"tri~uoromethyl#methyllead in 18) yield[ Tetrakis"tri~uoromethyl#lead has not been prepared and must be expected to be rather unstable like the analogous tetrahalolead complexes ð81JOM"327#46Ł[ "iv# Trihalomethylzinc\ !cadmium and !mercury\ CHal2MR "M Zn\ Cd\ H`"II## compounds Miller et al[ failed to prepare trihalomethylzinc iodides or bromides from zinc and tri! haloiodomethanes or trihalobromomethanes in glyme ð46JA3048Ł whereas Burton and Wiemers
135
Four Halo`ens or Three Halo`ens and One Other Heteroatom
did so by treating activated "acid washed# zinc or cadmium with dibromodi~uoromethane or bromochlorodi~uoromethane in DMF for 1 h at RT[ When dichlorodi~uoromethane was used\ the reaction had to be carried out at 79>C in a sealed ampoule[ A yield of 79Ð84) of "tri! ~uoromethyl#cadmium halide and a yield of 79Ð74) of "tri~uoromethyl#zinc halide was achieved[ The "tri~uoromethyl#metal halides were not isolated but stored for later use as 0 M solutions in DMF ð74JA4903Ł[ Bis"tri~uoromethyl#cadmium "00) yield\ 88) purity# and bis"tri~uoromethyl#zinc "7) yield# were prepared at low temperature "³34>C# by the reaction of the metal with hexa~uoroethane in a radio frequency discharge[ The {{naked||\ that is nondonor stabilized\ compounds Cd"CF2#1 and Zn"CF2#1 decompose at 9>C and −39>C\ respectively\ but may be stabilized with glyme ðCd"CF2#1 = glymeŁ and pyridine ðZn"CF2#1 = 1pyridineŁ ð75JA3092\ 80CJC216Ł[ The bis"tri~uoro! methyl#cadmium glyme adduct may also be prepared from dimethylcadmium and bis"tri~uoro! methyl#mercury in glyme ð79CC560\ 70JA1884\ 75JA721Ł[ Alkali metal tetrakis"tri~uoromethyl#cadmates have been prepared and investigated by NMR\ but not puri_ed ð78JOM"257#020Ł[ The formation of "tri~uoromethyl#mercury iodide is accomplished photochemically in 79) yield by treatment of tri~uoroiodomethane with mercury at 049>C ð37JCS1077Ł[ Further treatment of this isolatable intermediate with cadmium amalgam at 019Ð029>C causes the formation of bis"tri! ~uoromethyl#mercury in 79Ð89) yield ð38JCS1842Ł[ Bis"tri~uoromethyl#mercury is also formed from mercury"II# oxide and tris"tri~uoromethyl#phosphine upon 11 h heating at 099>C in a sealed tube "73) yield# ð59JA4648Ł[ "Trichloromethyl#mercury"II# chloride and bis"trichloro! methyl#mercury have been prepared\ by halide substitution\ from mercury"II# chloride or mercuric bromide with sodium trichloroacetate[ The intermediate mercury"II# trichloroacetate decomposes into the trichloromethyl derivative with elimination of carbon dioxide[ The reaction is conducted in diglyme at re~ux temperature for 0 h with yields of 58Ð66)[ The actual ratio of sodium trichloroacetate to mercury"II# chloride determines whether the product is bis"trichloro! methyl#mercury or the "trichloromethyl# mercury"II# halide ð52JOC0018Ł[
"v# Trihalomethylcopper\ !silver and !`old\ CHal2MRn "M Cu"I#\ A`"I#\ Au"I#\ Au"III## compounds The tri~uoromethyl complexes of group 00 may be arranged into the following order of stability according to Nair and Morrison] AuCF2 ×AgCF2 ×CuCF2 ð78JOM"265#038Ł[ "Tri~uoromethyl#copper"I# is probably formed initially in some coupling reactions\ for example\ when tri~uoroiodomethane is heated "029Ð039>C# with metallic copper in DMF[ This intermediate is trapped by aryl iodides with formation of the corresponding tri~uoromethylarenes ð58TL3984\ 69CPB1223Ł[ This method has later been improved by Kobayashi et al[ to include the corresponding reaction with aliphatic halides[ They shook tri~uoroiodomethane and copper powder in HMPA at 019>C for 1[4 h[ After removal of excess copper powder the aliphatic halide was added and the mixture stirred at RT or 69>C under N1 atmosphere[ They were able to tri~uoromethylate aliphatic and vinylic halides in 02Ð70) yield by the "tri~uoromethyl#copper"II# iodide formed in situ ð68TL3960Ł[ The "tri~uoromethyl#silver"I# trimethylphosphine complex has been prepared from silver acetate and Cd"CF2#1 = glyme in Et1O^ after 09 min trimethylphosphine was condensed into the reaction vessel[ The "tri~uoromethyl#silver"I# trimethylphosphine complex\ ð"CF2#AgPMe2Ł was isolated in 25) yield ð78JOM"265#038Ł[ "Tri~uoromethyl#gold"I# complexes stabilized "air and moisture insensitive# by trimethyl!\ triethyl! or triphenylphosphine ""CF2#AuL\ L PMe2\ PEt2 or PPh2# have been prepared in 54Ð64) yield from ClAuL "L PMe2\ PEt2 or PPh2# and Cd"CF2#1 = glyme in CH1Cl1[ Bis"tri~uoromethyl#mercury was ine}ective as a tri~uoromethylating agent\ even at 049>C ð78JOM"265#038\ 78OM0387Ł[ These gold"I# complexes are oxidized by elemental bromine or iodine with formation of phosphine stabil! ized "tri~uoromethyl#gold"III# dihalides in ½24) yield ""CF2#AuX1L\ L PMe2\ PEt2 or PPh2#[ The analogous addition of tri~uoroiodomethane to "CF2#AuL "L PMe2 or PEt2# in CH1Cl1 leads to bis"tri~uoromethyl#gold"III# iodide in 79) yield "87) cis\ 1) trans# ð78JOM"265#038\ 78OM0387Ł[ The unstable tris"tri~uoromethyl#gold"III# complex has been prepared by Guerra et al[\ from gold vapors and plasma!generated tri~uoromethyl radicals at −085>C ð75JOM"296#C47Ł\ and may also be obtained as the trimethylphosphine stabilized analog ð"CF2#2Au"PMe2#Ł by reaction of "CF2#1! AuI"PMe2# with Cd"CF2#1 = glyme in the presence of excess tri~uoroiodomethane in 79) yield
Three Halo`ens
136
ð78OM0387Ł[ The organogold"I# complex ð"CF2#Au"−C2N¦0Me#Ł was prepared similarly by Dryden et al[ in 67) yield ð81CM868Ł[ Nair and Morrison made ð"CF2#2Au"PEt2#Ł in 19Ð49) yield from CF2I and ð"CF2#Au"PEt2#Ł ð78JOM"265#038Ł[ Bis"tri~uoromethyl#gold"III# m!halide dimers ðAu"CF2#1"m!X#Ł1 have also been prepared\ by a vapor deposition technique\ from gold treated with excess "0 ] 099# of either bromotri~uoromethane or tri~uoroiodomethane[ The products may be recrystallized from pentane and are moderately air and light sensitive[ The m!bromide was isolated in 05) yield wheras the m!iodide was isolated in 7) yield ð89IC2141Ł[
"vi# Miscellaneous trihalomethyl transition metal\ CHal2MRn "M transition metal# compounds A number of platinum complexes containing tri~uoromethyl as a ligand have been prepared by ligand exchange from Pt"CF2#nMe1−nNBD "NBD\ norbornadiene# ð82JOM"342#296Ł[ This complex is itself made from PtMe1NBD by tri~uoromethyl:methyl exchange with CF2I ð77JOM"231#288\ 82JOM"342#188Ł[ Tri~uoromethyl:methyl exchange has also been used to prepare other platinum complexes containing tri~uoromethyl as a ligand ð89IC1385Ł[ Tri~uoroiodomethane adds to cis!PtMe1L1 "L PMe1Ph# at 079>C under vacuum to give PtMe1L1"CF2#I with CF2 and I in axial positions ð69IC1445Ł[ Hydrido tri~uoromethyl complexes of platinum"II# have been prepared by Michelin et al[ ð89OM0338\ 78JCS"D#0038Ł[ Other transition metal complexes with tri~uoromethyl as ligand have been prepared[ These include rhodium ð89JOM"277#280\ 80CC054Ł\ ruthenium ð89JOM"284#216\ 89JOM"286#198Ł\ osmium ð89JOM"284#216Ł\ iridium ð89JOM"283#504Ł\ manganese ð50JA0487Ł and cobalt complexes ð50JA2482Ł[
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
Comprehensive Organic Functional Group Transformations
6.08 Functions Containing Two Halogens and Two Other Heteroatom Substituents ANASTASSIOS VARVOGLIS University of Thessaloniki, Greece 5[97[0 INTRODUCTION
149
5[97[1 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS 5[97[1[0 Two Halo`ens and Two Oxy`en Functions 5[97[1[0[0 Di~uoro compounds 5[97[1[0[1 Dichloro and dibromo compounds 5[97[1[1 Two Halo`ens and Two Sulfur Functions 5[97[1[1[0 Di~uoro compounds 5[97[1[1[1 Dichloro\ dibromo\ and diiodo compounds 5[97[1[2 Two Halo`ens\ an Oxy`en\ and a Sulfur Function 5[97[1[3 Two Halo`ens and Other Chalco`en Functions 5[97[2 TWO HALOGENS AND ONE CHALCOGEN FUNCTION 5[97[2[0 Two Halo`ens\ a Chalco`en\ and a Nitro`en Function 5[97[2[0[0 Oxy`en compounds 5[97[2[0[1 Sulfur compounds 5[97[2[1 Two Halo`ens\ a Chalco`en\ and Other Functions 5[97[3 TWO HALOGENS AND TWO GROUP 04 ELEMENT FUNCTIONS 5[97[3[0 Two Halo`ens and Two Nitro`en Functions 5[97[3[0[0 Diamines and their derivatives 5[97[3[0[1 Dinitro compounds 5[97[3[0[2 Cyclic compounds 5[97[3[1 Two Halo`ens and Two Phosphorus Functions 5[97[3[1[0 Bis"phosphonates# 5[97[3[1[1 Cyclic compounds 5[97[3[1[2 Miscellaneous compounds 5[97[3[2 Two Halo`ens and Two Other Group 04 Element Functions
149 149 149 140 141 141 143 144 145 145 145 145 146 147 147 147 147 159 150 152 152 153 154 155
5[97[4 TWO HALOGENS AND ONE GROUP 04 ELEMENT FUNCTION
155
5[97[4[0 Two Halo`ens\ a Phosphorus\ and a Metalloid or Metal Function
155
5[97[5 TWO HALOGENS AND TWO METALLOID FUNCTIONS 5[97[5[0 Two Halo`ens and Two Silicon Functions 5[97[5[0[0 Linear carbosilanes 5[97[5[0[1 Cyclic carbosilanes 5[97[5[1 Two Halo`ens and Two Boron or Other Metalloid Functions 5[97[6 TWO HALOGENS AND ONE METALLOID FUNCTION 5[97[6[0 Two Halo`ens\ a Silicon\ and a Metal Function 5[97[7 TWO HALOGENS AND TWO METAL FUNCTIONS
138
156 156 156 157 158 158 158 169
149
Two Halo`ens and Two Other Heteroatoms
5[97[0 INTRODUCTION A great variety of functionalities characterize the family of compounds containing functions with two halogens and two other heteroatom substituents^ however\ the family has few representatives[ Heteroatom substituents include O\ S\ Se\ Te\ B\ N\ P\ As\ Si\ Ge\ and some metals\ and the halogen atoms are F and Cl in most cases[ Several members of the family stand on the verge of organic and inorganic chemistry\ particularly when relatively small molecules are involved without hydrogen atoms[ It is emphasized that the experimental work with elemental ~uorine requires special con! ditions and considerable expertise[
5[97[1 TWO HALOGENS AND TWO CHALCOGEN FUNCTIONS 5[97[1[0 Two Halogens and Two Oxygen Functions 5[97[1[0[0 Di~uoro compounds Addition of ~uorine to the carbonyl bond of simple per~uorooxo compounds leads to the formation of either stable adducts "`em!~uorohypo~uorites# or to products of further trans! formation[ In the case of FC"O#OF "0#\ both types of product may be formed[ Thus\ the simplest compound of this class\ di~uorodioxirane "3#\ has been obtained from "0# and either ~uorine or chlorine ~uoride in a ~ow system using a pelletized caesium ~uoride catalyst[ After the initial attack of ~uoride on carbon\ an electron transfer follows between "1# and the halogen^ the free radical intermediate "2# cyclizes to "3#\ or may produce "4# when ClF is used "Scheme 0# ð82AG"E#894Ł[ Bis"~uoroxy#di~uoromethane was the unique product obtained from the reaction between FC"O#OF and ~uorine\ again in the presence of caesium ~uoride\ in a Monel bomb "Equation "0## ð56JA4050Ł[ The same product was also formed from the double addition of ~uorine to CO1\ catalyzed by caesium ~uoride ð56JA0798\ 56JA0851Ł[ A variation involves the action of ~uorine upon sodium tri~uoroacetate or sodium oxalate ð56JA0700Ł[ Another hypo~uorite\ the peroxide "6#\ was produced by the addition of ~uorine to the carbonyl bonds of "5# "Equation "1## ð56CC769Ł[ In some esters of thionocarbonic acid the C1S group was directly transformed into CF1 upon treatment with ~uorine^ in this way\ compounds of the type "RCH1O#1CF1 were formed "where R is a polynitromethyl group# ð78IZV002\ 82IZV1402Ł[ Similar compounds were obtained by substitution from the cor! responding CCl1 analogues and SbF4 in SO1Cl1[ O F
O–
F
CsF, RT
F
OF (1)
O•
F
F2 or ClF
F
OF (2)
F
O O
F
OF (3)
(4) 20–50%
F
OCl
F
OF
+ (5) 0–70%
Scheme 1
O + F2
F
CsF, RT
OF
F
(1) F
OF
OF
O F
O
O
O (6)
OF F
+ 2F2
KF, –95 °C
F F
O
O
F F
(2)
FO (7)
Bis"~uoroxy#di~uoromethane reacts with halogenated alkenes\ probably through the free radical "2# which transfers its OCF1O group to the double bond[ The products are either halogenated acetals of methanal\ for example "7#\ or 0\2!dioxolanes\ for example "8# "Scheme 1#[ Upon treatment of the latter with Zn and K1CO2 in DMF\ chlorine was eliminated and per~uoro!0\2!dioxole was produced ð57IC513\ 81EUP388046\ 81EUP388047\ 81JFC"47#032\ 81JFC"47#189Ł[ Photochemically\ F1C"OF#1 also adds its OCF1O group to the double bond of per~uoro Dewar benzene^ the reaction is complex and the major product "5) yield# "09# rearranges thermally to "00# "Scheme 2#[ ð68JOC1702Ł[ Cyclic
140
Two Chalco`ens
thionocarbonates have been converted into 1\1!di~uoro!0\2!dioxolanes by ~uorinolysis of the C1S function using Bu3NH1F2 and N!iodosuccinimide ð83SL140Ł[ F
F3CF2CO
OCF2CF3
F
F
Cl
F , –180 °C
F
F
F
OF
F
OF
Cl Cl
Cl
F
F
F
F O
O
F
F (9)
(8) 90% Scheme 2
F
F F
F
F
OF
+ F
F
F
hν
F
F F
O
OF
F
F O
F
F
∆
F F O
F
O
F
O
O F
F
F (10)
F F (11)
Scheme 3
Some di~uorodialkoxymethanes are produced in a di}erent way\ after halogenolysis of the double bond of either F2CN1C"OR#1 or F4SN1C"OR#1 by chlorine ~uoride "Equation "2## ð89JFC"37#284Ł[ In some cases ~uorine can substitute for hydrogen attached to an sp2 carbon[ Per~uorodi! methoxymethane and per~uoro!0\2!dioxane*as well as other products*have been reported to result from electrochemical ~uorination of methyl 2!methoxypropionate ð65ZOR656Ł[ The physical properties of such compounds have been described but their preparation has not yet been docu! mented ð81MI 597!90\ 82MI 597!90Ł[ Chemical and electrochemical methods have been used to ~uorinate the methanal derivative "01# to "02# "Equation "3## ð80JFC"44#202Ł[ OCH2CF3 N F3C
F
OCH2CF3
F
OCH2CF3
F
OCF2CF2SO2F
F
OCF2CF2SO2F
+ F3CNCl2
+ 2ClF OCH2CF3
OCF2CF2SO2F OCF2CF2SO2F (12)
F2, NaF
(3)
(4)
(13)
The action of ~uorine on polymethylene oxide gives mainly a per~uoropolymer\ but it also brings about ~uorinolysis\ with partial ~uorination and depolymerization^ among the products identi_ed were F2COCF1OCF1H and HF1COCF1OCF1H ð70JCS"P0#0210Ł[ Chlorine in F1CCl1 is substituted by two ~uorosulfato groups in its reaction with ClOSO1F^ F1CBr1 reacts similarly with the peroxy compound FO1SOOSO1F[ In both cases the product is F1C"OSO1F#1 ð54IC0717\ 63IZV224Ł[ Ozonation of tetra~uoroethylene gave rise to an apparently stable moleozonide ð57CI"M#086Ł[ Singlet oxygen reacted with tetra~uoroethylene at −49>C to produce peroxidic per~uoroethers\ which upon strong and prolonged heating were converted into a mixture containing\ inter alia\ per~uoro!0\2!dioxetane\ per~uoro!0\2\4!trioxane\ and per~uoro!0\2\4\6!tetraoxocane ð61GEP1000585Ł[ In another patent\ the reaction of the adduct from the reaction between "F1N#1C1NF and KCN with F1C"OF#1 is claimed to give a mixture of products\ including the peroxide F2COOCF1OF ð60USP2474107Ł[ The unusual compound F2COOCF1OOOCF2\ bearing both peroxide and trioxide functions\ was formed among other products from a complex reaction between F1C"OF#1 and CsOCF2 ð60IC1068Ł[
5[97[1[0[1 Dichloro and dibromo compounds The number of compounds in this category is few[ The compounds can be obtained either by carbonyl "or thiocarbonyl# transformation or by chlorination of a methylene group[ Dichloro! diphenoxymethane "03# was produced upon heating diphenyl carbonate with PCl4^ similarly\ phenylene carbonate gave 1\1!dichloro!benzo!0\2!dioxole "04# ð50CB433\ 71JHC0194Ł[ Some diethyl
141
Two Halo`ens and Two Other Heteroatoms
thionocarbonates of the general formula "RCH1O#1C1S "where R is CF2\ CF1NO1 or CF"NO1#1# were converted into the corresponding CCl1 compounds using either SO1Cl1 or Cl1 ð78IZV002Ł[ Photochemical chlorination of 0\2!dioxolane converted it into its perchloro analogue "05# ð61JOC0347Ł[ Some dichlorobis"aryloxy#methanes were similarly prepared via radical!induced chlori! nation of the formaldehyde diaryl acetals with SO1Cl1 or Cl1 ð77S850Ł[ Dibromomethylal\ CBr1"OMe#1\ was obtained by simply dropping Br1 into cooled methylal ð11AG378Ł[
Cl
OPh
O
Cl
Cl
OPh (14)
O
Cl
Cl
Cl
O
O
Cl
Cl Cl Cl (16)
(15)
5[97[1[1 Two Halogens and Two Sulfur Functions 5[97[1[1[0 Di~uoro compounds The reaction of ~uorine with thiocarbonyl compounds usually gives addition products in which sulfur has also been oxidized[ Carbon disul_de is thus converted into the isolable compound "06# and subsequently into "07# "Scheme 3# ð66IC1863Ł[ The yield of "07# increased when caesium ~uoride was used as a catalyst^ chlorine ~uoride reacts in a similar way\ leading to the formation of "trans! ClSF3#1CF1 ð72JFC"12#214Ł[ The pseudohalogen CF2SF was also added to carbon disul_de^ no oxidation occurred and the double adduct "CF2SS#1CF1 was obtained in high yield ð81ZN"B#258Ł[ The related reaction of F1C1S with CF2SCl gave the adduct "F2CS#CF1SCl ð57CB1506Ł[ The same product was formed upon addition of ClF to F2CSC"S#F\ while a related addition of ClF occurred to the C1S bond of FC"S#SCN ð63CZ098Ł[ Compound "06# reacts with metal ~uorides\ a}ording relatively stable anions or cations[ For example\ with CsF a symmetrically bridged anion was formed\ while with AsF4 in liquid SO1 the stable sulfonium salt F1C"SF2#SF1¦AsF5− resulted ð80CB0242\ 81CC0906Ł[ When BF2 in SO1 was used\ "06# a}orded the solvolysis product "08#\ as a mixture of two diastereoisomers[ With silylated amines\ "08# was converted into sul_nimides\ for example "19# or "10# "Scheme 4#[ From the reaction between "08# and HCl\ the rather unstable F1C"S"O#Cl#1 was produced\ which upon hydrolysis gave the bis"sul_nic acid# F1C"SO1H#1[ Direct ~uorination at an sp2 carbon has been e}ected in some cases\ for example with "11# which was converted into "12#^ this was hydrolyzed to the sulfonic acid "14# through its salt "13# "Scheme 5# ð89IC3477Ł[
CS2
F2/He, –120 °C
F
SF3
F
SF3
F2/He, –80 °C
F
(17) Scheme 4
O
O
F
S NMe2
F
S NMe2
Me2N-TMS
O
SF5 F SO2F (22)
F2, NaF
F F
SF5
SF5 (18)
O
F
F
S
F
S
F F
MeN(TMS)2
F
S
F
S
NMe
F
O
(19) Scheme 5
(21)
O (20)
SF5
F
Ba(OH)2
(F5SCF2SO3)2Ba
H+
F F
SO2F (24)
(23) Scheme 6
SF5 SO3H (25)
142
Two Chalco`ens
Electrochemical methods have been used for the preparation of "07# and F1C"SO1F#1 ð48JA463\ While the latter was formed from CH1"SO1F#1 in 79) yield\ the former was one of many products into which 0\2\4!trithiane was transformed\ for example\ F2CSF3CF1SF4\ and the trithianic derivative "CF1SF3#2[ A di}erent approach was used for the preparation of the sulfone\ PhSO1CF1SPh\ which was obtained from the reaction of PhSO1CHF1 and aqueous NaOH in a two! phase system "CH1Cl1 with Aliquat 225#^ the sulfone was oxidized with H1O1 to F1C"SO1Ph#1 ð78JFC"32#42Ł[ A fairly large family of perhalogenated 0\2!dithietanes and their sulfur derivatives is known[ Photochemical dimerization of thiophosgene leads in a straightforward way to the formation of "15# ð22CB456Ł[ Upon treatment with SbF4\ this gives rise mainly to compound "16#\ along with some mono! and dichloroper~uoro!0\2!dithietanes "Scheme 6# ð54JOC0264Ł[ A related method started with compound "17#\ which was converted by strong acids into the isolable salt "18#^ treatment with caesium ~uoride a}orded the tri~uorodithietane "29# "Scheme 7# ð76CB318Ł[ A similar compound to "18# is the salt "20#\ which can undergo a variety of transformations at its carbocationic center\ as shown in Scheme 8 ð89CB0524Ł[ 75JFC"21#78Ł[
Cl
hν
2
Cl
S
Cl
SbF5
F
S
F
Cl
S
Cl
60%
F
S
F
S Cl
(26)
(27)
Scheme 7
F S
2
F
HF/SbF5 or FSO3H/SbF5
X
X
S
+
F SbF6–
F–
S
(28) X = Cl or SCF3
F
S
F
X
S
F
(30)
(29) Scheme 8
F
S
F
S
+
F AsF6– F
(31) X–,
F
S
S
SO2, RT
F Na2S2O3
BaCS3
F
F X S X = F, Cl, Br, I
F
S
F
S
F
S
S F
F
S
F
S
+
SCF3 AsF6–
O
S
Scheme 9
The majority of the reactions of per~uoro!0\2!dithietane involve oxidation at the sulfur[ Depend! ing on the oxidant and the conditions\ several products can be obtained using ~uorine or xenon di~uoride ð73JFC"15#248\ 78JFC"34#114Ł^ chlorine ~uoride ð62JFC"2#06\ 81CB424Ł^ chromium trioxide ð79AG"E#192Ł^ tri~uoromethyl hypochlorite or per~uoro!t!butyl hypochlorite ð66JA3083\ 67IC1062\ 68JA4838\ 70JA395\ 75IC164Ł^ and tri~uoromethaneperoxysulfonic acid ð72CB0512Ł[ Examples of the oxidation products are the structures "21#Ð"24#[ When "24# was heated with chlorine ~uoride\ it was transformed into the open chain compound F2CSO1CF1SF3Cl ð81CB424Ł[
F F
O2 S S O2 (32)
F
F
F
F
F4 S S F4 (33)
F F
OCF3 F3CO S F F F F S OCF3 F3CO (34)
F F
F4 S S O2 (35)
F F
143
Two Halo`ens and Two Other Heteroatoms
5[97[1[1[1 Dichloro\ dibromo\ and diiodo compounds Halogenated 0\2!dithietanes result from the photochemical dimerization of chloro! ~uorothiophosgene\ chlorobromothiophosgene\ and dibromothiophosgene ð65CB2321\ 66CB805\ 76CB0388Ł[ Tetrabromo!0\2!dithietane was also obtained from its tetrachloro analogue by sub! stitution using BBr2\ in 67) yield ð66CB805Ł[ These compounds\ along with tetrachloro!0\2!dithi! etane undergo various reactions at either carbon or sulfur\ in much the same way as tetra~uoro! 0\2!dithietane ð22CB456\ 66CB805\ 72CB0512\ 76SUL48\ 77JFC"28#218Ł[ Some transformations of the parent disulfone 0\0\2\2!tetraoxo!0\2!dithietane "25# are of interest] it can be halogenated by aqueous chlorine or bromine\ a}ording tetrachloro or tetrabromo disulfones in high yields "an analogous iodination does not occur#[ Chlorination was also e}ected using C3F8SO1Cl and Et2N[ The tetra! chlorodisulfone "26#\ upon mild hydrolysis\ was converted quantitatively into the sulfonic acid "27# "Scheme 09#[ Trichloro disulfone "39# was obtained from the silylated disulfone "28# upon treatment with butyllithium and C3F8SO1Cl:Et2N "Equation "4## ð72CB0174\ 74CB1197Ł[ Treatment of dibro! mothiophosgene "Br1C1S# with ozone at −79>C resulted in its partial trimerization^ hexabromo! 0\2\4!trithiane was formed in 4) yield ð66CB805Ł[ O2 S
Cl2/H2O, RT
Cl
88%
Cl
S O2
O2 S S O2
(36)
Cl
O2 S
Cl
H2O, 40 °C
Cl
SO3H
Cl Cl
(37)
Cl
(38)
Scheme 10
O2 S TMS
i, BuLi ii, C4F9SO2Cl/Et3N
TMS
Cl
(39)
(5)
Cl Cl
S O2
O2 S S O2 (40)
Bis"halogenated# open chain `em!disulfones exist for all four halogens^ some have been known since the end of the nineteenth century\ for example Br1C"SO1Et#1 ð0789CB2115Ł[ They may be produced by direct chlorination or bromination of `em!disulfones using aqueous halogen^ sulfuryl chloride or sulfuryl bromide may also be used ð24JA106\ 62JOC2247\ 64CJC1553\ 64JOC0167\ 79CJC0885\ 77ZOR0216Ł[ The trisulfone of 0\2\4!trithiane has been fully chlorinated photochemically\ while trithiane itself can be converted directly into the same product\ that is\ hexachloro!0\0\2\2\4\4! hexaoxo!0\2\4!trithiane "30#\ when heated with aqueous chlorine and MoO2 ð52JPR0\ 53ZC346Ł[ An interesting transformation of this trisulfone occurred when it was heated with SbF2 and catalytic amounts of SbCl4 in sulfolane\ resulting in the isolation of "31#[ The hexabromo analogue of "30# gave the tetrabromo analogue of "31# under milder conditions\ in dioxaneÐwater[ With tertiary amines or phosphines\ these trisulfones a}orded stable salts such as "32# "Scheme 00# ð75CB2520Ł[ Under certain conditions*when 0\2\4!trithiane is treated with sodium hypochlorite in an alkaline environment*chlorination occurs\ but oxidation stops at the disulfone stage and "33# is produced ð45JCS497Ł[ When treated with a tertiary amine\ the monosulfone of hexachloro!0\2\4!trithiane was converted to "34# ð57USP2265203Ł[ Cl
O2 S
Cl O2S
–
SO2
Cl
Cl (43)
O2 Cl S
Cl
Cl Et3NH+
Et3N
Cl SO2
Cl O2S Cl
Cl (41)
Cl
Cl
O 2S
SO2
SbF3/SbCl5, sulfolane, 190 °C
Cl Cl (42) 62%
Scheme 11
The potassium salts of monohalogenated `em!disulfones have also been halogenated "Equation "5## ð62JOC2247Ł[ Phenyliodonium ylides undergo brominolysis\ a}ording dibromo!`em!disulfones ð89CC0348\ 80CC369Ł[ Alternatively\ the halosuccinimides NCS\ NBS and NIS give the corresponding dihalodisulfones "Equation "6## ð77JCR"S#295Ł[ Chlorination of a methylene group in some sulfones bearing another sulfur!containing group has been e}ected by aqueous chlorine in acetic acid^ in
144
Two Chalco`ens O2 Cl S
Cl
Cl S
Cl
Cl O2S
SO2
Cl
Cl
Cl (44)
Cl
S Cl O2 (45)
some cases further transformations led to the isolation of interesting products\ as depicted in Scheme 01 ð45JCS497\ 64CJC1553\ 79CJC0885\ 72CJC509\ 80CJC1016Ł[ N!Chlorosuccinimide and sulfuryl chloride were used in order to convert H1C"SO1Cl#1 into Cl1C"SO1Cl#1 ð65CZ280Ł[ F3CSO2 –
X2, CCl4
Y K+
F3CSO2
X
F3CSO2
Y
(6)
F3CSO2 X = Y = Br X = Y = Cl O SO2Ph PhI
+
CH2Cl2, RT
NI
2
I
SO2Ph
I
SO2Ph 79%
(7)
SO2Ph O Cl2, AcOH
MeSO2CH2SH or MeSO2CH2SO2OPh
MeSO2CCl2SO2OPh
Cl2/H2O
MeSO2CCl2SO2Cl
MeSO2CH2SCH2Ph AcOH NaOCl
4-ClC6H4SCH2SO3Na
4-ClC6H4SO2CCl2SO3Na
Scheme 12
The transformation of a thiocarbonyl group into CCl1 can be achieved by chlorination[ One example involved photochemical addition of chlorine to carbon disul_de^ the dichloromethane bis"sulfuryl chloride#\ Cl1C"SCl#1\ formed initially was used for the preparation of the heterocycle "35# "Scheme 02# ð89JCS"P0#498Ł[ In another example\ the heterocycle "36# was heated in a sealed tube with PCl4 and was converted directly into "37# "Equation "7## ð80CB1914Ł[ Cl2
CS2
hν
ClS Cl
SCl
N
TMS-N=S=N-TMS
S
56%
Cl
S
N S
Cl
Cl (46)
Scheme 13 F 3C
S S
F3C
S
PCl5 ∆
F3C
S
Cl
F3C
S
Cl
(8)
(47)
(48)
5[97[1[2 Two Halogens\ an Oxygen\ and a Sulfur Function Only one compound of this type is known[ It was obtained from the addition of chlorine to either MeOC"S#SMe or MeOC"S#SSC"S#OMe\ both of which a}orded the same product\ MeOCCl1SCl ð42JA3471\ 45JA5969Ł[
145
Two Halo`ens and Two Other Heteroatoms
5[97[1[3 Two Halogens and Other Chalcogen Functions Tetra~uoro!\ tetrachloro!\ and tetrabromo!0\2!diselenetanes are known[ The ~uoro compound "49# was obtained by heating polymeric F1C1Se\ which in turn was formed from the boron compound "38# "Scheme 03# ð65ZAAC"316#003Ł[ Treatment of "49# with BCl2 or BBr2 gave its tetra! chloro or tetrabromo analogues[ 0!Tri~uoromethyl!0\2\2!tri~uoro!0\2!diselenetane was formed from the interaction of "CF2CF1Se#1Hg and "CF2Se#1Hg\ followed by treatment with Et1AlI ð80CB40Ł[ Two cyclic ethers*oxetane and tetrahydropyran "40#*were converted into "42# when treated with the selenoxide "41# and acetic anhydride\ in a Pummerer!type reaction "Equation "8## ð82TL0200Ł[ Tetra~uoro!0\2!ditelluretane was obtained by thermolysis of Me2SnTeCF2\ which initially "at −085>C# gave the monomer F1C1Te ð81C67Ł[ The same compound "43# was produced from the reaction of Hg"TeCF2#1 with two equivalents of Et1AlI^ when the monomer F1C1Te was allowed to react with F1C1Se\ tetra~uoro!0\2!selenatelluretane "44# was formed[ Compound "43# was converted into its tetrachloro analogue with BCl2 ð82JCS"D#1436Ł[ F
KF
B(SeCF3)3
∆
Se
∆
F polymeric
(49)
F
Se
F
F
Se
F
(50)
Scheme 14 O O
F
+
Ac2O, CH2Cl2
Se
X
Ph
AcOCH2XOCF2SePh
(9)
F
(51) X = CH2 or (CH2)3
(52)
(53)
F
Te
F
F
Se
F
F
Te (54)
F
F
Te (55)
F
5[97[2 TWO HALOGENS AND ONE CHALCOGEN FUNCTION 5[97[2[0 Two Halogens\ a Chalcogen\ and a Nitrogen Function 5[97[2[0[0 Oxygen compounds Per~uoromethyleneimine "N!~uorocarbonimidic di~uoride# "45# is a good precursor for the prep! aration of several compounds in this category\ especially compound "47#\ through the addition of FSO1OX "46# to its double bond "Equation "09##[ The related compound FSO1OCF1N"OSO1F#F was also obtained from "45# and the peroxide FO1SOOSO1F ð72IC794Ł[ However\ the reaction between F1C1NCl and FSO1OX led to the formation of a di}erent product\ that is\ the azo compound FSO1OCF1N1NCF1OSO1F ð73JOC2489Ł[ Other additions to the double bond of per! halogenated imines include the reactions in Scheme 04 ð65JA2418\ 72JOC3733\ 76AG"E#203\ 89JFC"37#284Ł[ Some of these compounds were cyclized to form oxaziridines\ upon reaction with metal ~uorides at a low temperature "Scheme 05# ð65JA2418\ 68IC808\ 79IC0229\ 72JOC3733Ł[ Direct epoxidation of per~uoroazaalkenes is not normally possible\ except with F1C1NCF2 which\ with mcpba\ gave the corresponding oxaziridine in 49) yield ð82JOC3643Ł[ F NF
+
FSO2OX
FSO2OCF2NFX
(10)
F (56)
(57)
(58) X = F, Cl, Br
Oxaziridine "48# underwent cycloaddition reactions with tetrahalogenated ethylenes and also with methyl ketones\ a}ording _ve!membered heterocycles such as "59# and "50# "Scheme 06# ð71JA3923\
146
One Chalco`en Cl
+
NCl
F5SOCCl2NCl2
F5SOCl
Cl F NCF3
+
F3COOH
F3COOCF2NHCF3
NCF2CFClX
+
F3COOH
F3COOCF2NHCF2CFClX
F F F
X = F, Cl or Br (CF3)2N NCF3
+
–F3CNCl2
2 ClF
(CF3)2NCF2OCH2CF3
F3CCH2O Scheme 15 F
O F
KHF2, –196 °C
F3COOCF2NHCF2CFClX
F NaF, –196 °C
F3COOCF2NHCF3
Cl
N
X F
F
F
O
F
N CF3
i, F3CO2H ii, NaF
F NSF5
F
O
F
N
F
SF5 Scheme 16
75JOC3355Ł[
The per~uoro oxazolidine "59# was also formed in low yield upon pyrolysis of per! ~uoromorpholine ð54JCS5966Ł[ The same compound and some related per~uoro!0\2!oxazolidines "51#Ð"53# were produced electrochemically from various precursors ð45JA4526\ 47JA0778\ 89JFC"37#146Ł[ The potassium and caesium salts of F1NCF1OH have been formed upon reaction of di~uo! roaminocarbonyl ~uoride "F1NCOF# with KF or CsF ð56IC0600Ł[ F
F
O
F
N CF3
F
X
F
Y
F
O
F
N
F Y
X (60)
X, Y = halogens
F3C
RCOMe
F
(59) F
O N O
R
F3C (61) Scheme 17 F F F3C
O N F (62)
F F CF3
F F F 3C
O
F N(CF3)2 F
N F (63)
F F F5C2
O N
F F F
F (64)
5[97[2[0[1 Sulfur compounds Some unusual reactions have been reported with thiocyanates and ~uorine[ Methyl thiocyanate was converted into F4SCF1NF1 when heated with elemental ~uorine ð48JA2488Ł[ Potassium or silver
147
Two Halo`ens and Two Other Heteroatoms
thiocyanate in the presence of catalytic amounts of CaF1 gave\ among several other products\ FSCF1NF1 ð54ZOB0301Ł[ An interesting conversion of compound "54# occurred upon its treatment with triethylamine\ when the zwitterion "55# was obtained "Equation "00## ð89AG"E#59Ł[ The anal! ogous reaction between "56# and quinuclidine "57# resulted in the formation of another zwitterion\ "58# "Equation "01## ð78AG"E#110Ł[ O2 S
F
F
THF, –70 °C
+ 2 Et3N F
S
F
S O2 (67)
(11)
(66) F
+ F
2 Et3N+CF2SO2–
F
S O2 (65)
+
N CF2SCF2SO2–
N
(12)
F (68)
(69)
Addition of chlorine to "69# gave "60#[ Upon heating this was converted into a mixture of heterocycles "61# and "62# "Scheme 07# ð60CB1621Ł[ Compound "61# was converted by Hg"SCF2#1 into F2CSSCF1NCS\ while "69# added photochemically F2CSCl to a}ord F2CSSCFCl "NCS#[ S
F
Cl2
F
Cl
NCS (70)
Cl
F
SCl
70 °C
F
N S
NCS
S (72)
(71)
+
Cl
N S
Cl
S (73)
Cl
Scheme 18
5[97[2[1 Two Halogens\ a Chalcogen\ and Other Functions Per~uoro!1!phosphapropene\ F2CP1CF1\ when added to methanol forms F2CPHCF1OMe^ C1F4P1CF1 reacts similarly ð75ZN"B#038\ 89ZN"B#037Ł[ The sul_nic salt "64# was obtained from "63# and sodium sul_te or sodium dithionite^ its oxidation with H1O1 gave the corresponding sulfonate and\ upon acidi_cation\ the free acid "Equation "02## ð78JA0662Ł[ A similar reaction occurred using "EtO#1P"O#CFBr1 and Na1S1O3 ð78CJC0684Ł[ The halogenated sulfones "65# were converted to "66# when their anion attacked PhHgCl "Equation "03## ð63JOM"60#224Ł[ Another organometallic mercury compound\ HOHgCI1SO2Na\ was obtained from the reaction of HgO and CHI1SO2Na ð24CB0402Ł[ O (EtO)2P F
O Br
+
Na2SO3
F
SO2Na
F
(13)
F
(75)
(74)
PhSO2CHX2
(EtO)2P
+
PhHgCl
ButOK, THF, –60 °C
(76)
PhSO2CX2HgPh
(14)
(77) X = Cl, Br
5[97[3 TWO HALOGENS AND TWO GROUP 04 ELEMENT FUNCTIONS 5[97[3[0 Two Halogens and Two Nitrogen Functions 5[97[3[0[0 Diamines and their derivatives The simplest compound of this class is per~uorodiaminomethane "68#\ which can be prepared by ~uorination either of cyanuric chloride "67# or of aminoiminomethane!sul_nic acid "79# "Scheme
Two Group 04 Elements
148
08# ð54ZOB0301\ 55JOC3121Ł[ The C!monochloro analogue of "68#\ that is FClC"NF1#1\ was formed from per~uoroguanidine and ClNO1 ð67IZV375Ł[ Tetramethylurea was converted into "Me1N#1CF1 when treated with COF1 in the presence of NaF ð51JA3164Ł[ Fluorine or chlorine ~uoride adds to the nitrile function in some per~uorocyanamides\ with the formation of perhalogenated methane! diamines\ as illustrated in Scheme 19 ð89JA617\ 81IC377Ł[ Chlorine ~uoride has also been added to the N1C bond of some halogenated imines\ in the presence of CsF^ for example\ "70# was converted into "71# "Equation "04## ð89JFC"37#284Ł[ A related addition of ClF occurred to the C1N bond of "73#\ which was obtained from "72# and LiORf "where Rf is a per~uoro group# "Equation "05## ð81JFC"46#182Ł[ When "73# "n 0\ Rf C"CF2#1CH2# was treated with C5F4SiMe2 and CsF\ ~uorine at the sp1 carbon was replaced by the C5F4 group ð82IC3791Ł[ Cl N
F2, 125 °C
N
Cl
N
Cl
F
NF2
F
NF2
(78)
NH
F2
H2N
(79)
SO2H (80)
Scheme 19
(CF3)2N
N
(CF3)2N
N
F3CN(F)
N
F2, CsF
(CF3)2NCF2NF2
ClF
(CF3)2NCF2NCl2
ClF
F3CN(F)CF2NCl2
Scheme 20
(CF3)2NC(F)
NCF3
ClF, CsF
(CF3)2NCF2NCl(CF3)
(81)
(15)
(82)
F (CF3)2NCF2N
F(2–n)
LiORf
(CF3)2NCF2N
(16) (ORf)n
F (83)
(84)
Insertion of alkenes and nitriles into the N0Cl bond of "71#\ as well as photolytic reactions of the latter with SF4Cl and CF2COCl\ occur readily ð89JFC"37#284Ł[ Several higher halogenated `em! diamines were produced in a similar way from "74# and halogenated alkenes which inserted into the N0Cl bond thermally^ for example "75# was obtained using CF11CClF "Equation "06## ð81IC377Ł[ When photolyzed alone "75# formed the imine "72# in high yield^ in the presence of halogenated alkenes\ insertion occurred and compounds such as "76# were formed "Scheme 10#[ Photolysis of the simpler N!chlorodiamine "71# led to the formation of the diazane derivative "77# "Equation "07##[ Compound "71# added to 0\0!di~uoroethylene and tri~uoroethylene on irradiation forming adducts such as "78# "Equation "08##[ F
F
F
Cl
∆
+
(CF3)2NCF2NCl2 (85)
(CF3)2NCF2N(Cl)CF2CCl2F
(17)
(86)
F
CH2CCl2F (CF3)2NCF2N CF2CCl2F (87)
F , hν
Cl (CF3)2NCF2N CF2CCl2F (86) Scheme 21
F
hν, –CCl3F
N (CF3)2NCF2 (83)
F
159
Two Halo`ens and Two Other Heteroatoms Cl
hν
(CF3)NCF2N
(CF3)NCF2N(CF3)N(CF3)CF2N(CF3)2
(18)
CF3 (82)
(88)
F
Cl
hν
+
(CF3)2NCF2N
(CF3)2NCF2N(CF3)CH2CClF2
(19)
F
CF3 (82)
(89)
Chlorine ~uoride has also been added to the C1N bond of a per~uorohydrazone^ the adduct\ upon irradiation with UV light\ was converted into a complex tetrazane having two CF1 groups ~anked by nitrogen functions ð78IC2234Ł[ A related per~uorohydrazone\ "89#\ added a methyl group and ~uorine to its double bond upon reaction with iodomethane and silver ~uoride^ compound "80# was formed "Equation "19## ð81IC3806Ł[ Some di~uoromethylene `em!diamines with alkyl or phenyl groups are also known[ A `em!diamine with two phenyl groups\ PhNHCF1NHPh\ was prepared from PhNHCF2 and aniline ð48ZOB1058Ł[ The bis"azo compound# O1NC5H3N1NCF1N1 NC5H3NO1 was the product from the reaction of di~uorodinitromethane with 3!nitroaniline ð81IC218Ł[ The preparation of the nitramine F1NCF1NO1 from CF1"OF#1 and F1NC"F#1NF has been described ð57USP2276922Ł[ A simple amine derivative\ di~uoro"bisisocyanato#methane "82#\ was produced upon thermolysis of "81# "Equation "10## ð73JOC3430Ł[ Some sulfur!containing amine derivatives have been reported\ derived from various simple compounds bearing a cyano group^ some examples are illustrated in Scheme 11 ð56MI 597!90\ 57ZN"B#632\ 75CB096Ł[ F
MeI, AgF
(CF3)2NN(Me)CF2N(CF3)N(CF3)2
(CF3)2NN N(CF3)N(CF3)2 (90) TMS-O TMS-O
(91) O-TMS
N
N
∆
O-TMS
SF4
N
F2S(O)N
N
F2S
F4SO
N
N
F
F N
F2S
F2SN
Br2, HgF2
N
F2S(O)N
N
N
SF4
N
NBr2
F2S O
F N
SF2 F O
F Cl2, HgF2
NCO (93)
SF2 F O
N
F2S
F2S
F
SF2
F F2S(O)N
NCO
N
F
O
F
(21)
F F (92)
H2N
(20)
N F
NCl2 F
Scheme 22
5[97[3[0[1 Dinitro compounds Di"halo#dinitromethanes of the general formula X1C"NO1#1 are known with all four halogens^ some mixed halogen compounds have also been reported[ Dichloro! and dibromodinitromethanes are formed in several degradative reactions of a variety of precursors "too many to mention in the space available here# by nitric acid[ The conversion of 1\3\5!trichloro! and 1\3\5!tribromoaniline into dichloro! and dibromodinitromethane\ respectively\ is an important preparative method
Two Group 04 Elements
150
ð33JOC308Ł[ A more conventional method for the preparation of dibromodinitromethane involved the reaction of sodium dinitromethanide with bromine after treatment with butyllithium\ or directly with bromine in THFÐHMPA "hexamethylphosphoramide# ð78ZOR1389Ł[ Phenyliodonium dinitro! methylide was converted in high yields into either dichloro! or dibromodinitromethane with the appropriate halogen\ NCS or NBS "Equation "11## ð67IZV1237Ł[ The very unstable diiodo! dinitromethane was reported to be formed upon acidi_cation of potassium iododinitromethanide ð13JCS331Ł[ Di~uorodinitromethane "84# was _rst prepared from di~uorodiazirine "83# and N1O3 "Equation "12## ð53JHC122Ł[ The same substrate "83#\ which on photolysis generates di~uorocarbene\ gave a 4) yield of "84# with NO^ the photochemical reaction of di~uorodiiodomethane in excess NO a}orded a 09) yield of "84# ð81IC218Ł[ The reactions of potassium trinitromethanide with ~uorineÐsodium ~uoride and also with potassium ~uoride again led to the formation of "84# ð57IZV318\ 57JOC2962Ł[ Di~uorodinitromethane was also formed in 27) yield from the reaction of di~uoronitroacetic acid with XeF1^ in a similar way\ ~uorochloronitroacetic acid produced ~uorochlorodinitromethane ð77IZV355\ 77IZV1528Ł[ The same compound was obtained when chlorotrinitromethane was treated with CsF in DMF ð69IZV1442Ł[ Chlorobromodinitro! methane was prepared from chlorine and ammonium bromodinitromethanide^ the latter was formed from dibromodinitromethane in liquid ammonia "Equation "13## ð33JOC308Ł[ O NO2
+
PhI
or
X2
X
NO2
X
NO2
NX
(22)
NO2 O X = Cl, Br F
N N
F
+
hν, –N2
N2O4
(94) Br
NO2
NO2
NH3
Br Br
NO2
–
NH4+ NO2
F
NO2
F
NO2 (95)
(23)
Cl2
Br
NO2
Cl
NO2
(24)
5[97[3[0[2 Cyclic compounds Several methods have been developed for the preparation of the important heterocycle di~uo! rodiazirine "83#[ Historically\ the _rst method involved cyclization of F1C"NF1#1 by ferrocene ð55JHC134Ł[ The same substrate was converted more e.ciently into "83# using tetrabutylammonium iodide "Scheme 12# ð56JOC0833\ 57JOC0736Ł[ Tetra~uoroformamidine "85# was also transformed e.ciently into "83#\ using either ferrocene or potassium iodide ð56JOC3934\ 57JOC0736Ł[ Tetra~uoro! formamidine was isomerized by potassium ~uoride at a low temperature to per~uorodiaziridine "86#\ an unstable compound which frequently exploded] with ferrocene this gave "83#^ when heated with caesium ~uoride it dimerized to form "87# "Scheme 13# ð57JOC2378Ł[ Curiously\ compound "87# was claimed in a patent to be a possible heat transfer ~uid ð81JAP93009272Ł[ A unique rearrangement leading to the formation of "83# occurred when di~uorocyanamide "F1NCN# was treated with caesium ~uoride at room temperature ð55IC0344Ł[ Chloro~uorodiazirine was obtained from di! chlorobis"di~uoramino#methane\ Cl1C"NF1#1\ after treatment with boric acid^ the precursor was prepared from per~uoroguanidine\ HCl and HNO2 ð56JOC0833\ 56USP2244381Ł[ Some further per! halogenated diaziridines are compounds "88#Ð"091#[ Their preparation involved the use of CsF or KF as catalysts at low temperatures[ Compound "88# was obtained from CF11NF or CF2N"F#C"F#1NF ð72JOC660Ł[ Compound "099# was formed from CF11NCl^ on treatment with mercury in tri~uoroacetic acid\ chlorine was replaced by hydrogen ð73JOC2489Ł[ Compound "090# was formed from CF11NF and CF11NBr\ which _rst gave CF2N"F#C"F#1NBr ð77JOC3332Ł[ Compound "091# was prepared from CF11NF and CF11NCF2 ð89JA617Ł[ Fluorine and chlorine*from either ClF or a mixture of chlorine and mercury di~uoride*readily add to cyanuric ~uoride "092# a}ording compound "093# "Equation "14## ð64MI 597!90\ 75CB096Ł[ Fluorine added to "092# in a complex way^ in addition to the per~uoro analogue of "093#\ per~uoro!
151
Two Halo`ens and Two Other Heteroatoms F
NF2
Bu4N+ I–
F
N
KF, MeCN/H2O
F
NF2
100%
F
N
100%
NF NF2
F
(94)
(96)
Scheme 23
F F
N
F 2N
N
F NF
KF, –160 °C
NF2
F
F
N
F
N
CsF, dimer
(96)
NF2
F
F
F (98)
(97) Scheme 24
F F
N
F
N
Cl F
N
F
N
CF3
Br F
N
F
N
CF3
(99)
CF3 F
N
F
N
CF3
(100)
CF3
(101)
(102)
0\2!diazolidine and noncyclic compounds such as CF2N"F#CF1N"F#CF2 were formed ð51JA1640Ł[ Per~uoro!1\4!diazahexa!1\3!diene "094#\ when heated with CsF\ was cyclized to a mixture of isomeric 0\2!diazolines "095# and "096#[ In acetonitrile in the presence of CsF\ both products gave the anion "097#\ which reacted with alkyl halides a}ording N!alkyl compounds\ for example "098# with iodomethane[ Compounds "097#\ "095# and "096# also underwent ~uoride ion induced reactions with per~uoroalkenes^ the main product\ when per~uorocyclopentene was used was "009# "Scheme 14# ð74JCS"P0#0080Ł[ The per~uoro analogue of "098# was converted to 1\1!dichloro! or 1\1!dibromo! dimethyl!0\2!diazolidine ð73JFC"13#346Ł[ Another heterocycle "001#\ was formed from "000# upon heating with CsF^ when irradiated in the presence of CsF\ "000# was transformed into a complex dimer "Equation "15## ð89HAC056\ 81ICA416Ł[ Compound "001# was also formed upon dimerization of "095# and "096# ð74JCS"P0#0080Ł[
N
F
F ClF or Cl2 + HgF2
N
Cl
F
Cl
N
Cl
N
F
Cl
F (103)
N
N
F
Cl
(104)
F F
F NCF3
F3CN
(25)
Cl
F F
F
CsF, 220 °C
F3C F
N
+
N
F3C
N
N
F F (107) 16%
F (106) 65%
(105)
F
F
MeCN, F– F
F
F F3C
N
N
F
F
F
F F
F F F
F
F
F F
F
F F
F3C F
(110)
F
F
F F F
F N
N–
F
F
(108) Scheme 25
MeI
F
F F3C
N
N
F
F
(109)
Me
Two Group 04 Elements
152
F F F
NCClF2 CsF, 110 °C
F 3C NCClF2
F
FF
F N
N
F
F (112)
(111)
F N CF3
N
(26)
F F
5[97[3[1 Two Halogens and Two Phosphorus Functions 5[97[3[1[0 Bis"phosphonates# The study of these compounds has been intensi_ed since two important discoveries were made] "i# the ability of Cl1C"PO2H1#1 "clodronic acid\ "004## to help in the process of bone formation^ and "ii# the various physiological properties of nucleotide analogues\ especially ATP\ in which an oxygen atom in the triphosphate unit is replaced by a di~uoromethylene group ð67JCE659\ 73JCS"P0#0008Ł[ Bis"halogenated# methylenebisphosphonic acids are usually prepared through halogenation of the appropriate tetraesters\ which are subsequently hydrolyzed[ The ester Cl1C"PO"OEt#1#1 was obtained in 61) yield by heating H1C"PO"OEt#1#1 with PCl4 at 039>C ð59ZOB0591Ł[ However\ the cheaper commercially available isopropyl tetraester "002# is the preferred starting material[ This was con! verted into its dichloro derivative "003# and then hydrolyzed to the acid "004# by heating in concentrated hydrochloric acid "Scheme 15# ð55BEP561194\ 57JOM"02#088\ 74JOM"180#034Ł[ The dibromo analogues and the relatively unstable diiodo analogues of "003# were prepared in a similar way by the hypohalite method ð60JOC0724Ł[ Several other tetraesters "symmetrical or mixed# of the general formula X1C"PO2R1#1 "where R was an alkyl group and X was chlorine or bromine# were prepared by the hypohalite method^ in which careful control of temperature\ pH\ and reaction time led to high yields ð81JCS"P1#724\ 81PS"69#072Ł[ The ester "003# was also converted to the acid "004# without hydrolysis by heating in sym!tetrachloroethane\ with evolution of propene ð56JOC3000Ł[ Since this acid is highly polar\ it was desirable to prepare some partial ester derivatives[ This was achieved via two methods] silyl derivatives and selective hydrolysis[ The _rst method was based on the obser! vations that the rate of silylation of methyl!containing mixed tetraesters follows the order methyl ×primary alkyl×secondary alkyl\ whereas the hydrolysis rate of silyl and alkyl esters follows the order SiMe2 ×tertiary alkyl×secondary alkyl×primary alkyl[ Taking into account these factors\ the preparation of several tri!\ di!\ and mono!esters was e}ected[ For example\ the ester "005# was converted _rst to "006# and then to the salt "007# in 76) yield "Scheme 16#[ The second approach was suitable for n!alkyl esters\ since branched chain alkyl groups in acidic conditions undergo hydrolysis faster than n!alkyl groups[ Thus\ "008# was transformed into "019# in 33) yield "Scheme 17# ð82TL3440Ł[ O P(OPri)2
O i, Na/toluene ii, Cl2 or NaOCl
P(OPri)2
Cl
P(OPri)2
Cl
P(OPri)2
O (113)
O HCl
Cl
P(OH)2
∆
Cl
P(OH)2
O
O
(114)
(115)
Scheme 26
Cl Cl O
O
O
P(OPri)2
P(OPri)2
P OPri OMe
(116)
TMS-Cl, NaI, MeCN
Cl
∆
Cl O
P OPri O-TMS
(117)
O MeOH, NaOH
P(OPri)2
Cl Cl O
P OPri ONa
(118)
Scheme 27
Di~uoro tetraesters\ as well as the free bisphosphonic acid "011# which is an isopolar analogue of pyrophosphoric acid\ were prepared by several routes[ Fluorination of "010# with perchloryl ~uoride
153
Two Halo`ens and Two Other Heteroatoms O
O i, MeSO3H, toluene, ∆ ii, NaOH
Cl
P(OPri)2
Cl
P(OHex)2
Cl
P(ONa)2
Cl
P(OHex)2
O
O
(119) Hex = n-C6H13
(120) Scheme 28
in a strongly basic environment gave "011# in good yields "R Et or Pri#^ this was converted with trimethylsilyl bromide into the silyl derivative "012#\ which then was hydrolyzed to the free acid "013#\ isolated as its trisdicyclohexylammonium salt "Scheme 18# ð70JOC3462\ 71JFC"19#506Ł[ Acetyl hypo~uorite was also an e.cient ~uorinating agent ð80BMC246Ł[ Coupling reactions have also been used^ for example\ the lithium salt obtained from HCF1P"O#"OEt#1 and lithium diisopropylamide "LDA# gave\ on reaction with "EtO#1P"O#Cl\ the tetraester "EtO#1P"O#CF1P"O#"EtO#1 in 63) yield ð71TL1212Ł[ The reaction between BrF1CPO"OPri#1 and "PriO#1PONa also gave "011# "R Pri# ð70CC829Ł[ The same compound was formed using CBr1F1 and "PriO#1PONa^ the mixed halogen tetraester FBrC"PO"OPri#1#1 was obtained from FCH"PO"OPri#1#1 and tetraisopropyl pyro! phosphate\ upon treatment with bromine in aqueous K1CO2 ð77JOM"239#82Ł[ The application of the MichaelisÐBecker variation to the preparation of di~uoromethylene esters has also been described ð79JFC"04#152\ 71JFC"19#010Ł\ as have other routes to compounds of this type ð83JOC1282Ł[ O
O
O
P(OR)2
F
P(OR)2
F
P(O-TMS)2
F
P(OR)2
F
P(O-TMS)2
FClO3, ButOK
P(OR)2
TMS-Br
O
O
H2O
F F
O
(122)
(121)
O P(OH)2 P(OH)2 O
(123)
(124)
Scheme 29
Coupling of X1C"PO2H1#1 with 4?!phosphoromorpholidate of adenosine resulted in the formation of "014# ð73JCS"P0#0008Ł[ In the same way\ the CF1 analogue of 2?!azido!2!deoxythymidine tri! phosphate was obtained ð80BMC246Ł[ Other nucleotide analogues with a CF1 group in the place of an oxygen next to the _rst phosphorus atom\ of the general formula "015#\ were prepared from the tris"tetrabutylammonium# salt of F1C"PO2H1#1 and the tosylate of the nucleoside^ these initially gave the CF1 pyrophosphate analogues\ which were converted with phosphate into "015# ð80TL5314Ł[ Isopentenyl and geranyl di~uoromethylenephosphonates and some nucleotide analogues were also prepared using this methodology ð75JOC3657\ 76JA4431\ 76JOC0683Ł[ X XO HO3P
P
O
OH
O P
O O
adenine
OH
HO3P
O
O P OH
F F
O P
O O
base
OH
HO OH (125) X = F, Cl
HO (126)
5[97[3[1[1 Cyclic compounds Reaction of the ylides "016# with triphenylphosphine led to the formation of diphosphiranes "017# "Equation "16## ð79IJC"B#509Ł[ Similar compounds "029# were obtained stereospeci_cally from trans! diphosphene "018# and dichloro! or dibromocarbenes "Equation "17## ð76T0682Ł[ Yields became quantitative when sonication was applied ð80TL4854Ł[ Bis"tri~uoromethyl#phosphine "020#\ upon treatment with ZnMe1 or triethylamine\ was converted via F2CP1CF1 to 0\2!diphosphetane "021# "Equation "18## ð61CC562\ 72IC1462\ 74PS"10#238Ł[ Thermolysis of Me2SnP"CF2#1\ however\ was more e.cient^ this initially gave F2CP1CF1\ which was found to be fairly stable[ Depending on the
Two Group 04 Elements
154
conditions\ the thermolysis products could be either F2CP1CF1 or "021# "a mixture of cis and trans isomers#\ along with some trimer\ that is\ 1\3\5!tris"tri~uoromethyl#!0\2\4!triphosphorin ð73AG"E#609Ł[ Similar thermolysis at 9[990 torr "9[02 Pa# of Me1NP"SnMe2#CF2 resulted in the formation of the monomer Me1NP1CF1\ which underwent polymerization^ when the polymer was heated at 499Ð599>C\ the dimeric compound "022# was formed ð81ZN"B#210Ł[ Treatment of Cl1PCHCl1 with triethylamine led to the formation of "023# via ClP1CCl1 ð70ZOB1529Ł[ Another heterocycle "024# was formed from the reaction of Cl1P"S#CF1P"S#Cl1 and butylamine ð76CZ065Ł[ X
+
–
Ph3P
+
PPh3
X
Ph3P
X
Ph3P
X
(127) X = Cl, Br
(27)
(128)
Ar
Ar P
P
+
+
CHX3
KOH
Ar
P
X
P
X
(28)
Ar (130)
(129) Ar = 2, 4, 6-But3C6H2 X = Cl, Br F
F3C 2 (CF3)2PH
P
Et3N, – 2HF
F P
F
P F
Cl
Cl F
P
(133)
But P N
F
P Cl
CF3
Cl Cl
Cl NMe2
(29)
P F (132)
(131) Me2N
F
F
Cl
P Cl
F (135)
(134)
5[97[3[1[2 Miscellaneous compounds When Me2GePMe1 was heated in benzene with Hg"CF2#1\ a mixture of products was formed\ including Me1PCF1PMe1 ð67BSF"1#250Ł[ Both isomeric 0\2!diphosphetanes "021# reacted with meth! anol "the cis isomer reacted faster#\ a}ording F2CP"OMe#CF1P"CF2#CHF1 and other products of further methanolysis ð74IC037Ł[ The chlorophosphine Cl1PCHCl1\ when heated with triethylamine and PCl2\ was transformed into Cl1PCCl1PCl1 ð70ZOB1529Ł[ The monomeric F1C1PCF2 reacted with several dialkylphosphines forming "025#\ which upon heating with elemental sulfur a}orded "026# "Scheme 29# ð89ZN"B#188Ł[ Compound "027# was converted into several derivatives\ as illus! trated in Scheme 20 ð76CZ065Ł[ Carbon vapour reacted with PCl2 forming Cl1PCCl1PCl1 ð69JCS"A#20Ł[ Some chlorinated and ~uorinated bis"phosphoranium# salts of the general formula R2P¦C−"X#P¦R2X− are formed in solution when phosphines are treated with CCl3\ CFCl2\ or CFBr2 ð66S588\ 77JOC255Ł[
F PCF3 F
+
R2PH
R2PHCF2PHCF3 (136) Scheme 30
'S'
R2P(S)CF2PHCF3 (137)
155
Two Halo`ens and Two Other Heteroatoms (PriO)2P(S)CF2P(S)(OPri)2
PriOH
F2PCF2PF2
SbF3
Cl2P(S)CF2P(S)Cl2
TMS-NMe2
PhPCl2
(138)
(NMe2)2PCF2P(NMe2)2
Cl2PCF2PCl2
Scheme 31
5[97[3[2 Two Halogens and Two Other Group 04 Element Functions The sole compounds in this category are "039# and "030#\ which were obtained upon thermolysis of "028# "Equation "29## ð73AG"E#609Ł[ F Me3SnAs(CF3)2
∆
F3 C
F
F3C
+
As CF3
As
F
As
As
CF3 F
F F
F F cis and trans (140)
(139)
F
As
(30)
F
CF3 (141)
5[97[4 TWO HALOGENS AND ONE GROUP 04 ELEMENT FUNCTION 5[97[4[0 Two Halogens\ a Phosphorus\ and a Metalloid or Metal Function When reacted with butyllithium in THF solution\ diethyl trichloromethylphosphonate "031# gives the salt "032# which can be converted into "033# upon treatment with trimethylsilyl chloride "Scheme 21# ð62JOM"48#126Ł[ The same salt "032# was formed from diethyl chloromethylphosphonate upon treatment with butyllithium and then CCl3 ð64S424Ł[ The di~uoro analogue of "032# was similarly obtained in situ from diethyl di~uoromethylphosphonate and LDA[ With TMS!Cl this a}orded TMS!CF1P"O#"OEt#1 in 76) yield\ while with Bu2SnCl the phosphonate Bu2SnCF1P"O#"OEt#1 was obtained in 66) yield ð71TL1212Ł[ The salt LiCF1P"O#Ph1 was formed in situ from HCF1P"O#Ph1 and LDA ð89TL4460Ł[ Several compounds with a P0Ge bond\ mainly germylphospholanes\ under! went CF1 insertion into this bond^ the mildest way to produce di~uorocarbene was the thermal decomposition of Hg"CF2#1 in benzene ð67BSF"1#250Ł[ Upon reaction with metallic cadmium the phosphonate "034# was converted into the stable salts "035# and "036# "Equation "20## ð70JFC"07#086Ł[ The same phosphonate "034# reacted similarly with metallic zinc to a}ord BrZnCF1P"O#"OEt#1^ after several days in contact with PhHgCl\ this gave another stable organometallic compound\ PhHgCF1P"O#"OEt#1 ð78JOC502\ 89JFC"38#64Ł[ The related compound PhHgCCl1P"O#"OMe#1 was formed from PhHgCCl1Br and P"OMe#2 ð55JOM"4#074Ł[ The stable copper compounds BrM! CuCF1P"O#"EtO#1 "M Cd\ Zn# were produced from the corresponding cadmium or zinc phos! phonates and CuBr ð81T078Ł[ A stable rhodium complex containing the group PCF1P has been described ð89JOM"288#078Ł[ O Cl3C
Cl Cl Li
BuLi, THF, –80 °C
P(OEt)2 (142)
O P(OEt)2
Cl Cl TMS
TMS-Cl, –80 °C
(143) Scheme 32
F F Br
O P(OEt)2
(145)
Cd
F F BrCd
O P(OEt)2 (144)
O P(OEt)2
(146)
+
F F Cd F F
O P(OEt)2 (31) P(OEt)2 O (147)
156
Two Metalloids 5[97[5 TWO HALOGENS AND TWO METALLOID FUNCTIONS 5[97[5[0 Two Halogens and Two Silicon Functions
The chemistry of these compounds is dominated by the work of G[ Fritz on carbosilanes^ most of his results have been summarized in a book and a review article ðB!75MI 597!90\ 76AG"E#0000Ł[
5[97[5[0[0 Linear carbosilanes A simple compound of this class is perchloro!0\2!disilapropane "037#\ which was obtained by photochlorination of the main product resulting from the reaction between chloroform and elemen! tal silicon in the presence of copper ð47CB11Ł[ It was also produced by photochlorination of Cl2SiCH1SiCl2 ð46IZV088\ 53CB0562Ł[ Perchloro!0\2!disilapropane "037# readily replaced one or more of its silicon!bound chlorine atoms^ for example\ upon treatment with SbF2 or ZnF1 it was converted to "038# ð53CB0562\ 60AG"E#409\ 61ZAAC"280#108Ł[ Further transformations were e}ected with LiAlH3] to "049# and to "040# "the latter with one equivalent of MeMgCl# "Scheme 22# ð60ZAAC"271#8\ 60ZN"B#379Ł[ Interestingly\ MeLi methylated exclusively the carbon atom of compound "037#[ In contrast\ the reaction of "049# with MeLi was very complex\ the major products being MeH1Si CCl1SiH2 and CCl1!containing 0\2\4!trisilapentanes[ The reaction of "049# with MeMgCl was similarly complex^ however\ in the presence of a great excess of MeMgCl\ the main product was TMS!CH1SiHMe1 ð67ZAAC"330#014Ł[ Photobromination of Cl2SiCH1SiCl2 by BrCl readily a}orded Cl2SiCBr1SiCl2 ð65ZAAC"308#102Ł[ A well!studied compound related to "037# is "042#^ it has been prepared by several methods[ One method was by reaction of "038# with MeLi ð60ZN"B#379Ł[ Another approach involved lithiation of dichloromethane "two equivalents of BuLi# and subsequent reaction with trimethylsilyl chloride ð56JCS"C#0369\ 61JOC1551Ł[ Alternatively\ the lithiated "041# a}orded "042#\ again with TMS!Cl "Scheme 23# ð69JOM"12#250Ł[ A better yield was achieved upon insertion of dichlorocarbene into the Si0Si bond of "043#[ The dibromo analogue at the central carbon of "042# was prepared from TMS!CBr1Li and TMS!Cl\ and also from the complex TMS!BrP"NEt1#2 and TMS!Br ð69JOM"13#536\ 69TL3582\ 89ZOB698Ł[ Cl3Si
SiCl3
Cl
Cl
(148)
ZnF2
MeMgCl
LiAlH4
F3Si
H3Si
SiF3
Cl
Cl
Cl
(149)
Cl3Si
SiH3 Cl
SiMeCl2
Cl
(150)
Cl
(151)
Scheme 33
TMS
Li
Cl
Cl
(152)
TMS-Cl
TMS Cl
TMS Cl
(153) Scheme 34
CHCl3/KOH, 18-crown-6
TMS
TMS
61%
(154)
Partially chlorinated 1\1!dichloro!0\2!disilapropanes such as "044# and "045# were also obtained from "041# and Me1SiCl1 or MeSiCl2 "Scheme 24# ð68ZAAC"337#44Ł[ Starting with PhMe1SiCCl1Li\ similar compounds were also formed[ A di}erent method is also accessible for such compounds^ for example\ Cl2SiCCl1SiMeCl1 was obtained through methylation of "Cl2Si#1CCl1 with MeMgCl ð60ZN"B#379Ł[ Full methylation of "038# at the silicon resulted in the formation of "042#[ Apart from halogenated silapropanes\ some related 0\2\4!trisilapentanes were also studied[ Photochemical chlorination of "046# produced "047#\ which reacted further with ZnF1 and with MeMgCl in the same manner as "037# "Equation "21## ð67ZAAC"328#050Ł[ Partial chlorination of "046# is also possible\ using sulfuryl chloride and benzoyl peroxide ð60ZAAC"271#106Ł[ The most interesting reaction of "047# was methylation with MeMgCl] when MeMgCl was in large excess "07 ] 0#\ the main products were TMS!C2C!TMS "36)# and CH11C"TMS#CH"TMS#1 "13)# ð63ZAAC"393#092Ł[ The same
157
Two Halo`ens and Two Other Heteroatoms
reaction was studied with some ~uorinated silicon compounds such as F2SiCCl1SiF1CH1SiF2 and F2SiCCl1SiF1CHClSiF2 ð67ZAAC"328#050Ł[ An octahedral silicon complex has been described\ result! ing from the reaction between 1\1?!bipyridyl and "Cl2Si#1CCl1 ð89CB834Ł[ TMS Cl
SiMeCl2
MeSiCl3
Cl (155)
TMS
Li
Cl
Cl
TMS
Me2SiCl2
Cl
Cl SiCl3
Si Cl
Cl (156)
(152) Scheme 35
Cl3Si
SiMe2Cl
Cl Cl
Cl
Cl2, hν
Cl3Si
Cl
SiCl3
Si Cl
(32)
Cl (158)
(157)
A fair number of di~uorocarbodisilanes are known[ Several disilanes of the general formula "048# and other related compounds reacted readily with di~uorocarbene\ produced by thermolysis of Me2SnCF2^ the products "059# resulted from CF1 insertion into the Si0Si bond "Equation "22##[ Some trisilanes also reacted in the same way[ For example\ FMe1Si"SiMe1#SiMe1F\ which was converted by single or double CF1 insertion to FMe1SiCF1SiMe1SiMe1F or "FMe1SiCF1#1SiMe1[ Compound "059# "X F# can react with Grignard and organolithium compounds "MeMgCl\ MeLi\ PhLi\ etc[#^ one or both silicon!bound ~uorine atoms are then replaced by an alkyl or phenyl group\ so that with MeLi either TMS!CF1SiMe1F or "TMS#1CF1 is obtained[ Other reactions at the Si0F bond in "FMe1Si#1CF1 involved LiAlH3\ which converted it to "HMe1Si#1CF1\ and Me1PLi\ which produced Me1PMe1SiCF1SiMe1F as well as "Me1PSiMe1#1CF1 ð72AG"E#629Ł[ XMe2Si
SiMe2X
[CF2]
XMe2Si F
(159)
SiMe2X
(33)
F
(160) X = F, Cl, Br, OMe
5[97[5[0[1 Cyclic carbosilanes Reaction of Cl2SiCH1CH1SiCl1CH1Cl with magnesium produced 0\2!disilacyclopentane "050#\ which upon photochlorination eventually gave the fully chlorinated compound "051# "Scheme 25#[ An interesting solvent e}ect was observed in the reaction of "051# with an excess of MeMgCl^ while in ether several products were formed\ the main product "55) yield# being Cl1C1CClSiMe1CCl1! TMS\ in pentane\ compound "052# was formed exclusively ð69ZAAC"261#10\ 68ZAAC"347#26Ł[ When MeSiCl2 or Me1SiCl1 are heated at 699>C\ they are converted to the cyclic carbosilane "053#\ which upon photochlorination a}ords the perchloro compound "054# "Scheme 26# ð59ZAAC"292#74Ł[ The partially brominated "055# was obtained from the photochemical reaction of "053# and bromine chloride\ whereas the bromo analogue of "053# gave the octabromo analogue of "055# "Scheme 26# ð64ZAAC"308#102Ł[ The hexa~uoro analogue of "053# underwent photochlorination to produce a mixture of 1\1!dichloro!\ 1\1\3\3!tetrachloro!\ and 1\1\3\3\5\5!hexachloro!hexa~uoro trisilacyclo! hexanes ð64ZN"B#854Ł[ The reactivity of these compounds is analogous to that already mentioned for their linear analogues\ for example "054# was converted by LiAlH3 into 1\1\3\3\5\5!hexa! chlorotrisilacyclohexane ð60ZAAC"271#8Ł[ Unusual reactivity was\ however\ noted in the case of MeMgCl^ with "054#\ four equivalents of MeMgCl gave the ring!contracted "056# in high yield[ Further reaction of "056# with more MeMgCl a}orded several products\ the major being "057# "Scheme 27# ð62ZAAC"284#048\ 62ZAAC"288#179Ł[ Several partially chlorinated 0\2\4!trisilacyclohexanes are known\ some resulting from the interaction of "054# with its fully hydrogenated analogue\ that is "H1SiCH1#2 ð60ZAAC"271#106Ł[ Their reactivity with MeMgCl is of interest\ since di}erent products are obtained in each case depending on the structure of the substrate "Scheme 28#[ The reactivities of partly brominated trisilacyclohexanes with Grignard and organolithium compounds exhibit some similarity to and a number of di}erences from their chloro analogues^ the most notable di}erence is the double substitution of carbon!bound bromine by butyl groups when butyllithium is used "Equation "23##[ Generally\ more results are available in the carbosilane _eld\ with ample discussion and mechanistic details ðB!75MI 597!90Ł[
158
One Metalloid Cl Cl2Si
Cl2, hν
SiCl2
Cl
Cl2Si
Cl
SiCl2
Cl
Cl
Cl
Cl
Si
Cl
Br
Br
Cl
Cl
Cl Si
Si Cl
Si
SiMe2
Cl Cl (163)
Cl
Si Cl
Si
Cl
Cl
Cl
Cl
(166)
Cl Cl
hν, Cl2, CCl4, ∆
BrCl, hν
Cl
Cl
Me2Si
pentane
Cl Cl (162) Scheme 36
(161)
Cl
MeMgCl
Cl
Cl
Cl Si
Si Cl
Si Cl
(164)
Cl Cl
Cl
Cl
(165)
Scheme 37 Cl (165)
4MeMgCl
Cl
Cl
Cl2Si
MeMgCl
SiCl2
Cl
Cl
TMS
TMS
Cl Si Cl
TMS (167)
(168)
Scheme 38
Cl Cl2Si Cl Cl
SiCl2 Cl
Cl
H2Si
Si Cl Cl Cl
Si H2
MeMgCl
SiH2 Cl Si H2 Cl
Cl
MeMgCl
Cl Me2Si
H2Si Cl
SiH2
Cl
Me2Si
SiMe2
MeMgCl
Me2Si Cl
SiMe2 Si H2
SiMe2
Cl
SiMe2 Cl Si
Cl H Me
Scheme 39 Br Me2Si
Br SiMe2 Br
Bu BuLi
Si Me2 Br
Me2Si
Bu SiMe2 Br
(34)
Si Me2 Br
5[97[5[1 Two Halogens and Two Boron or Other Metalloid Functions Two compounds of this type are known[ The _rst is Cl1BCCl1BCl1\ which was formed when carbon vapour reacted with either BCl2 or B1Cl3 ð58JCS"A#0771Ł[ The other is Cl2GeCCl1GeCl2^ this was obtained in a similar way from carbon vapour and GeCl3 ð69JCS"A#20Ł[ 5[97[6 TWO HALOGENS AND ONE METALLOID FUNCTION 5[97[6[0 Two Halogens\ a Silicon\ and a Metal Function Apart from Grignard and organolithium compounds which exist only in solution "Section 5[97[5[0#\ some stable compounds of this category are known with tin and mercury[ They are
169
Two Halo`ens and Two Other Heteroatoms
normally formed from the appropriate organometallic compound coupled with metal or silyl chlorides^ in one case\ an exchange reaction between organomercurials was noted[ Examples are given in Scheme 39 ð69JOM"12#250\ 69JOM"13#563\ 60JOM"16#08Ł[ Dichlorocarbene insertion into the Si0Hg and Si0Ge bond also occurs\ but the products are further transformed ð56JOM"6#P19Ł[
TMS Cl
TMS
Li
Cl
Cl
Li
+
Cl
Br Me3Sn Br
Cl
HgCl Cl
TMS
HgCl
+
HgCl2 Li
Cl TMS
Hg
Cl
Cl Cl
Cl TMS
+
Br
+
Br
TMS
Br TMS
+ HgPh2
Cl
HgPh Cl
1– 2
Cl
Br
Me3Sn
TMS-Cl
TMS
SnMe3
Me3SnCl
Br MgCl
SnMe3
Cl
Cl TMS
TMS
TMS
+ Me3SnCl
Br
TMS
Hg
Cl
Cl Cl
TMS Cl
+
1– HgPh 2 2
Scheme 40
5[97[7 TWO HALOGENS AND TWO METAL FUNCTIONS Stable isolable compounds of this category involve tin[ Most were prepared by insertion of dihalocarbenes\ from organomercurial precursors or chloroform "Equation "24## ð56JA1689\ 58JA0843\ 80SRI390Ł[ Coupling of Me2SnCBr1!TMS with Me2SnCBr1MgCl also produced "Me2Sn#1CBr1 ð69JOM"13#536Ł[ The theoretically interesting dilithiodi~uoromethane was shown by ab initio cal! culations to have a planar lithium bridged structure of CLi1F¦ F− ion pair character ð74CC4Ł[ R3Sn
SnR3
+
[CX2]
R3Sn X
Copyright
#
1995, Elsevier Ltd. All R ights Reserved
SnR3
(35)
X
Comprehensive Organic Functional Group Transformations
6.09 Functions Containing One Halogen and Three Other Heteroatom Substituents ANGELA MARINETTI and PHILIPPE SAVIGNAC DCPH - Ecole Polytechnique, Palaiseau, France 5[98[0 ONE HALOGEN AND THREE CHALCOGENS 5[98[0[0 One Halo`en and Three Oxy`en Functions 5[98[0[1 One Halo`en\ Sulfur\ and Oxy`en Function 5[98[0[1[0 One halo`en and three sulfur functions 5[98[0[1[1 One halo`en\ two sulfur\ and one oxy`en function 5[98[0[2 One Halo`en\ Selenium\ and Sulfur Function 5[98[1 ONE HALOGEN AND TWO CHALCOGENS
161 161 162 162 165 165 166
5[98[1[0 One Halo`en\ Two Chalco`ens\ and a Nitro`en Function 5[98[1[1 One Halo`en\ Two Sulfur\ and a Phosphorus Function 5[98[1[2 One Halo`en\ Two Sulfur\ and a Metal Function 5[98[2 ONE HALOGEN AND ONE CHALCOGEN
166 167 167 168
5[98[2[0 One Halo`en\ One Chalco`en\ and Two Group 04 Elements 5[98[2[0[0 One halo`en\ one oxy`en\ and two nitro`en functions 5[98[2[0[1 One halo`en\ one sulfur\ and two nitro`en functions 5[98[2[0[2 One halo`en\ one chalco`en\ and two phosphorus functions 5[98[2[1 One Halo`en\ One Sulfur\ and Two Silicon Functions 5[98[3 ONE HALOGEN AND THREE GROUP 04 ELEMENTS 5[98[3[0 One Halo`en and Three Nitro`en Functions 5[98[3[0[0 Halotrinitromethanes 5[98[3[0[1 Miscellaneous halonitromethanes 5[98[3[0[2 Halotriaminomethanes 5[98[3[0[3 "Di~uoroamino#~uorodiazirine 5[98[3[0[4 Fluorine!containin` diaziridines 5[98[3[1 One Halo`en\ One Nitro`en\ and Two Phosphorus Functions 5[98[3[2 One Halo`en and Three Phosphorus Functions 5[98[4 ONE HALOGEN AND TWO GROUP 04 ELEMENTS
168 168 170 170 171 171 171 171 173 173 174 174 174 175 175 175 176
5[98[4[0 Metal Halodinitromethides 5[98[4[1 Metal Bis"phosphonyl#halomethides 5[98[5 ONE HALOGEN AND ONE GROUP 04 ELEMENT
177
5[98[6 ONE HALOGEN AND METALLOID FUNCTION "THREE\ TWO OR ONE\ TOGETHER WITH METALS#
178
5[98[6[0 One Halo`en and Three Metalloid Functions 5[98[6[0[0 Three silicon functions 5[98[6[0[1 Two silicon and a `ermanium function 5[98[6[0[2 Two silicon and a boron function 5[98[6[0[3 Three boron functions or two boron and a metal function
160
178 178 181 181 181
161
One Halo`en and Three Other Heteroatoms 182
5[98[6[1 One Halo`en\ Two Metalloid\ and One Metal Function 5[98[7 ACKNOWLEDGEMENTS
182
5[98[0 ONE HALOGEN AND THREE CHALCOGENS 5[98[0[0 One Halogen and Three Oxygen Functions Acyclic covalent halogenides having the general structure*one halogen and three oxygen func! tions*are known for chlorine and ~uorine[ In most cases\ the oxygen substituents are poly! ~uorinated or polynitrated groups[ Poly"nitro#alkyl chloro ortho!formates are reactive intermediates in the synthesis of explosive ortho!carbonates and are themselves explosive compounds ð72USP356604Ł[ They have been prepared by chlorination of the corresponding trichloromethyl disul_des "Scheme 0#^ their reaction with the HFÐpyridine complex yields ~uoro ortho!formates ð72JEM84Ł through a chlorineÐ~uorine exchange reaction[ Highly ~uorinated peroxide derivatives*exhibiting a better thermal stability than non! ~uorinated analogues*are prepared by CsF!catalyzed ~uorination of the corresponding carbonyl compounds "Equation "0## ð57JOC1984\ 65JFC"6#490Ł[ In both cases\ limitation of sample size and suitable safety equipment are required[ R
R O R
O
S S
Cl Cl Cl
+
O
Cl
Cl
Cl2
R
60 °C 95%
O
O
+ SCl2 + ClSCCl3
Cl O R
R R
R
O R
O
O Cl
+ HF/pyridine
25 °C 79%
O
R
O
F O
R
R R = C(NO2)2F Scheme 1
RO O
RO O FO RO O
CsF
+ F2
O
–78 °C
RO O
(1)
F
R = CF3, 100% SF5, 60%
Reaction of carbon tetrachloride with penta~uorophenol in the presence of aluminum chloride\ or with bromine ~uorosulfate\ gives the trisubstituted species in low yields and as a mixture with several by!products "Scheme 1# ð57IC323\ 77ZOR0402Ł[
CCl4 + F5C6OH
AlCl3 80 °C
CCl4 + FSO2OBr
22 °C
F5C6O F5C6O F5C6O 16% FSO2O FSO2O FSO2O
Cl
25% Scheme 2
Cl
+ (F5C6O)4C
+ ...
27% FSO2O
Cl
FSO2O
Cl
+
+ BrCl 50%
162
Three Chalco`ens 5[98[0[1 One Halogen\ Sulfur\ and Oxygen Function 5[98[0[1[0 One halogen and three sulfur functions "i# Acyclic covalent halo`enides
Compounds of this type have been reported with sul_de\ oligosul_de\ and sulfone substructures[ Polyhalogenated derivatives are by far the most numerous[ The principal methods of preparation are exempli_ed below[ "a# From thiocarbonyl compounds and halo`ens[ The oldest method of preparation was described by Hass and Klug ð55AG"E#734\ 57CB1598Ł[ This involves the rapid and quantitative addition of chlorine "or bromine# to bis"tri~uoromethyl# trithiocarbonate to give the sulfenyl chloride "Equation "1##[ Several examples of halogenations using chlorine and thionyl chloride have been described subsequently "Equation "2# and Table 0#[ Starting materials are either trithiocarbonates with strong electron withdrawing groups\ R0 and R1\ or sulfone derivatives[ Under similar conditions\ bromine and iodine failed to react with trithiocarbonate!S\S!dioxides "entries 1 and 2 in Table 0#[ F3CS S
+ Cl2 (or Br2)
–78 °C, 1h
F3CS
R1S
"X2"
S R2S
ClS F3CS F3CS 90% XS R1S R2S
Cl
(or
BrS F3CS F3CS 60%
Br )
(2)
(3)
X
Table 0 Halogenation of thiocarbonyl compounds[ Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ R1 Rea`ents and conditions Yield ")# Ref[ Entry R0 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * 0 CF2 CF2 FCl\ −79>C "mixture# 65CB0865 1 PhS PhSO1 Cl1\ CCl3 79 65CB0958 Cl1\ CCl3 77 65CB0958 2 PhS 3!Me[C5H3SO1 3 CN CN Cl1\ −09>C\ CH1Cl1 79 70CB0021 Cl2CS Cl1\ CCl3 80 73SUL74 4 Cl2CS 5 Cl2CCCl1S Cl2CCCl1S Cl1\ CCl3 099 74T4034 Cl2CS SO1Cl1\ CH1Cl1 87 74T4034 6 PhCH1 7 Me Me SO1Cl1\ −04>C\ pentane 42 73SUL130 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ *
Chlorination with chlorine or thionyl chloride is a very e.cient approach to sulfenyl chlorides] most of the reactions reported in Table 0 are rapid\ clean\ and quantitative[ The sulfenyl chlorides thus obtained are useful starting materials for the synthesis of more elaborate\ trisubstituted trithio ortho!formates[ The most signi_cant examples of nucleophilic substitution reactions of the SCl function by amines\ thiols\ and amides "Equation "3## are given in Table 1[ The reactivity of the S0Cl bond is generally increased by electron withdrawing substituents R0 and R1[ Some of the poly~uoro derivatives are claimed to be fungicidal agents\ and the synthesis of the phthalimido derivative "entry 1 in Table 1# has been patented ð69GEP0897579Ł[ XS R1S R2S
Nu–
X X = Cl or F
NuS R1S R2S
X
(4)
"b# From thiocarbonyl compounds and sulfenyl halo`enides[ Thiocarbonates having the general structure ðR"S#nSŁ1C1S "n 0\ 1 and 2# are formed from thallium or barium thiocarbonates by reaction with sulfenyl chlorides "Equation "4# and Table 2#[ When an excess of sulfenyl chloride is used\ the transient thiocarbonate reacts further to give the chlorothio ortho!formate in fair to moderate yields "entries 0 and 1 in Table 2#[ The synthesis of various polyhalogenated ortho! formates bearing disul_de or trisul_de units has also been reported ð74T4034Ł[
163
One Halo`en and Three Other Heteroatoms Table 1 Nucleophilic substitution reactions of sulfenyl chlorides[
Ð*ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ R1 Nu Conditions Yield ")# Ref[ R0 ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ * CF2 CF2 Et1NH petroleum 71 65CB0865 CF2 phthalimide C5H5\ Et2N 43 69GEP0897579\ 65CB0865 CF2 CF2 CF2 K!pyrrole pentane 55 72CB2214 Cl2CS Na phthalimide CH1Cl1\ H1O 49 74T4034 Cl2CS CF2 CF2 NH2 −79>C 56 63CZ098 morpholine CHCl2 89 65CB0958 PhS 3!Me[C5H3SO1 PhS Ph!SO1 morpholine CHCl2 76 65CB0958 PhS 3!Me[C5H3SO1 PhSH CHCl2 64 65CB0958 t Bu SH CHCl2 76 65CB0958 PhS 3!Me[C5H3SO1 3!Me[C5H3SO1Na C5H5 17 65CB0958 PhS 3!Me[C5H3SO1 PhS 3!Me[C5H3SO1 MeCOSH CCl3\ 49>C 84 75T628 CF2 AgCN 19>C 86 65CB0865 CF2 CF2 CF2 AgO
