A Specialist Periodical Report
Organophosphorus Chemistry Volume 7
A Review of the Literature Published between July 1974 and June 1975
Senior Reporter S m Trippett, Department of Chemistry, University of Leicester
Reporters R. S. Davidson, Universify of Leicester R. S. Edmundson, University of Bradford J. B. Hobbs, Max Planck Institot fiir Experimenfelle Medizin, W. Germany D. W. Hutchinson, Universify of Warwick R. Keat, Universify of Glasgow J. A. Miller, University of Dundee D. J. H. Smith, University of feicesfer J. C. Tebby, North Staffordshire Polytechnic B. J. Walker, Queen's University of Belfast
0Copyright 1976
The Chemical Society Burlington House, London W I V OBN
ISBN : 0 85186 066 4
ISSN :0306 0713 Library of Congress Catalog Card No. 73-268317
Printed in Great Britain by Adlard & Son, Ltd. Bartholomew Press, Dorking
Foreword
After the decline recorded in volume six, the number of publications in organophosphorus chemistry has again exceeded that in any previous year. This has meant even more selectivity on the part of Reporters. We are still able to cover all significant contributions, but the reader may detect a further condensation in style and a trend towards a catalogue approach. We hope to resist this trend in future volumes. Meanwhile, continued comments and criticism are welcome. S. Trippett
Contents
Chapter 1 Phosphines and Phosphonium Salts By D. J. H. Smith
1
1 1 1 2 4 6
1 Phosphines Preparation From Halogenophosphine and Organometallic Reagents From Metallated Phosphines By Addition of P-H to Olefins By Reduction Miscellaneous Reactions Nucleophilic Attack at Carbon Carbonyls Miscellaneous Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous
7 8 8 8 9 10 13 16
2 Phosphonium Salts Preparation Reactions Alkaline Hydrolysis Additions to Vinylphosphonium Salts Miscellaneous
17 17 19 19 21 23
3 Phospholes
24
4 Phosphorins Preparation Reactions
26 26 27
Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett
29
1 Introduction
29
2 Acyclic Systems
30
3 Four-membered Rings
30
Contents
Vi
4 Five-membered Rings Phospholens 1,3,2-Dioxaphospholans 1,3,2-Dioxaphospholens 1,2-0xaphospholens 1,3,2-Oxazaphospholidines Miscellaneous
41 41
5 Six-co-ordinate Species
42
Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller
33 33
34 37 39
45
1 Halogenophosphines Reactions with Organometallic Reagents Reactions with Simple Alkenes and Aromatics Reactions in which Phosphorus is Electrophilic Biphilic Reactions Ligand Exchanges between Phosphorus Groups Miscellaneous Silyl and Related Phosphines
45 46 49 49 54 56 57
2 Halogenophosphoranes Physical and Structural Aspects Preparation of Phosphoranes Reactions of Phosphoranes Synthetic Uses of Phosphine-Halocarbon Reactions
58 60 62 65
Chapter 4 Phosphine Oxides, Sulphides, and Selenides By J. A. Miller
45
58
66
1 Preparation and Structure
66
2 Reactions
71
3 Miscellaneous
76
Chapter 5 Tervalent Phosphorus Acids By B. J. Walker 1 Introduction
78 78
vii
Contents
78 78
2 Phosphorous Acid and its Derivatives Nucleophilic Reactions Attack on Saturated Carbon Attack on Unsaturated Carbon Attack on Nitrogen Attack on Oxygen Attack on Halogen Electrophilic Reactions Rearrangements Cyclic Esters of Phosphorous Acid Miscellaneous Reactions
101 103
3 Phosphonous and Phosphinous Acids and their Derivatives
104
Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson
78 80 89 90 94
97 99
105
1 Synthetic Methods General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives
105 105 105 108
2 Reactions General Reactions of Phosphoric Acid and its Derivatives Reactions of Phosphonic and Phosphinic Acid Derivatives
114 114 116 125
Chapter 7 Phosphates and Phosphonates of Biochemical Interest 131 By D. W. Hutchinson 1 Introduction
131
2 Coenzymes and Cofactors Nicotinamide Nucleot ides Flavin Coenzymes Pyridoxal Phosphates
131 131 133 133
3 Sugar Phosphates
134
4 Phospholipids Isoprenoid Lipids
136 136
5 Naturally Occurring Phosphonates
138
...
Contents
Vlll
6 Oxidative Phosphorylation
139
7 Enzymology Phosphoproteins Enzyme Mechanisms
141 141 142
8 Other Compounds of Biochemical Interest
145
Chapter 8 Nucleotides and Nucleic Acids By J. B. Hobbs
146
1 Introduction
146
2 Mononucleotides Chemical Synthesis Cyclic Nucleotides Affinity Chromatography
146 146 149 152
3 Nucleoside Polyphosphates Chemical Synthesis Affinity Labelling Met a1 Complexes
153 153 156 157
4 Oligo- and Poly-nucleotides Chemical Synthesis Enzymic Synthesis Sequencing
158 158 161 163
5 Analytical Techniques and Physical Methods Separation and Quantitation Structure Probes Radio1ysis
164 164 165 165
Chapter 9 Ylides and Related Compounds By S. Trippett 1 Methylenephosphoranes
Preparation Reactions Halides Carbonyls Miscellaneous
166
166 166 166 166 170 173
ix
Contents
2 Phosphoranes of Special Interest
174
3 Selected Applications of Ylides in Synthesis General Natural Products Macrocyclic Compounds
177 177 181 183
4 Selected Applications of Phosphonate Carbanions
183
Chapter 10 Phosphazenes By R. Keat
188
1 Introduction
188
2 Synthesis of Acyclic Phosphazenes From Amides and Phosphorus(v) Halides From Azides and Phosphorus(m) Compounds Other Methods
188 188 189 190
3 Properties of Acyclic Phosphazenes Halogeno-derivatives Alkyl and Aryl Derivatives
194 194 196
4 Synthesis of Cyclic Phosphazenes
201
5 Properties of Cyclic Phosphazenes Halogeno-derivatives Amino-derivatives Alkoxy- and Aryloxy-derivatives Alkanethiol Derivatives Alkyl and Aryl Derivatives
203 203 204 206 207 207
6 Polymeric Phosphazenes
208
7 Molecular Structures of Phosphazenes Determined by X-Ray Diffraction Methods
209
Chapter 11 Photochemical, Radical, and Deoxygenation Reactions 212 By R. S. Davidson 1 Photochemical Reactions
212
2 Phosphinidenes and Related Species
217
Contents
X
3 Reaction of Reactive Intermediates with Phosphorus-containing Compounds
218
4 Radical Reactions
219
5 Deoxygenation Reactions
223
6 Desulphurization Reactions
225
7 Deselenation Reactions
227
Chapter 12 Physical Methods By J. C, Tebby 1 Nuclear Magnetic Resonance Spectroscopy Chemical Shifts and Shielding Effects Phosphorus-31 8p of PI and PI1 compounds 6p of PI11 compounds 8p of P I V compounds 6p of P V compounds 8p of P V I compounds Fluorine-19 Carbon-12 Hydrogen-1 Studies of Equilibria, Shift Reagents, and Solvent Effects Pseudorotation Non-equivalence, Restricted Rot ation, Inversion, and Configuration Spin-Spin Coupling JPPand JPM JPF and JPN JPC
JPHand JPC,H J P C ~ X Hand JPXCH Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies
228
228 229 229 229 229 230 232 232 232 233 234 235 236 239 241 241 242 242 243 245 246
2 Electron Spin Resonance Spectroscopy
247
3 Vibrational Spectroscopy Stereochemical Aspects Studies of Bonding
250 25 1 253
4 Microwave Spectroscopy
254
xi
Contents
5 Electronic Spectroscopy Absorption Photoelectron Fluorescence
255 255 256 257
6 Rotation and Refraction
257
7 Diffraction
258 258 262
X-Ray
Electron 8 Dipole Moments, Permittivity, and Polarography
263
9 Mass Spectrometry
265
10 pKa and Thermochemical Studies
267
11 Chromatography and Surface Properties
268
Aut hor Index
271
Abbreviations
ADP AIBN AMP ATP CMP DBN DBU DCC DMF DMSO FAD GDP g.1.c. HMPT
HMT NAD NADP NBS NMN n.q.r. PPi TCNE TDAP TFAA THF t.1.c. UDPGal UDPGlc
adenosine 5’-pyrophosphate bisazoisobutyronitrile adenosine 5’-phosphate adenosine 5’-triphosphate cytidine 5’-phosphate 1,5-diazabicyclo[4,3,O]non-5-ene
1,5-diazabicyclo[5,4,O]undec-5-ene dicyclohexylcarbodi-imide NN-dimethylformamide dimethyl sulphoxide flavin-adenine dinucleotide guanosine 5’-pyrophosphate gas-liquid chromatography hexamethylphosphoric triamide hexamethylenetetramine nicotinamide-adenine dinucleotide nicotinamide-adenine dinucleotide phosphate N-bromosuccinimide nicotinamide mononucleotide nuclear quadrupole resonance inorganic pyrophosphate tetracyanoethylene tris(dimethy1amino)phosphine trifluoroacetic acid tetrahydrofuran thin-layer chromatography uridine 5’-pyrophosphate galactose uridine 5‘-pyrophosphate glucose
1 Phosphines and Phosphonium Salts BY D. J. H. SMITH
1 Phosphines Preparation.-From Halogenophosphine and Organometallic Reagents. 1,2-Phosphaboretens, e.g. (l), have been obtained from the reaction of sodium trialkyl-lalkynylborates with chloro-phosphines; with acetic acid they give (E)-alkenylph0sphines.l Lithium amino-acetylides react with chlorodiphenylphosphineto form (phosphino-ethyny1)amines(2).2 Et
+ Ph$‘Cl
Na[EhBC=CMe]
\
Et
/Me
-+
C=C EhB--]PPh, I I
-
’
‘C=C H
/Me
‘PPh,
(1)
LiC=CNR,
+ PhJ‘Cl
%P-C=CNR,
R = alkylor aryl-
(2)
Condensation of dimethyl methylphosphinite with chlorodiphenylphosphine at room temperature gave (3), which with an excess of chlorodiphenylphosphinegave tetraphenyldiph~sphine.~ The diphosphine(4) can be synthesizedby reaction of an excess of chloro(pheny1)-tbutylphosphine with chlorotrimethylsilanein the presence of magne~ium.~ 0
P&PC1
+ MeP(OMe),
II I OMe
-+ Ph,P-PMe
wp-pph,
(3) Ph 2
‘P--cI+
/
ph
/’h
‘P-P
Me$iCl
/
\
But
But
But
(4) 1 2 8
4
P. Binger and R. Koster, J . Organometallic Chem., 1974, 73, 205. G. Himbert and M. Regitz, Chem. Ber., 1974, 107, 2513. K. M. Abraham and J. R. van Wazer, Inorg. Chem., 1975, 14, 1099. H. Schumann and R. Fischer, J. Organometallic Chem., 1975, 88, C13.
1
2
Organophosphorus Chemistry
A wide range of 1,3-diphosphorinansand 1,3-diphospholans has been obtained from the reaction of alkali-metal diphosphides (5) and a variety of halide^.^ n
(5) = \
M = Naor Li R1 = Ph, alkyl, or H R2 = alkyl, H, or lone pair
n
PhP,
E = Si, Sn,P,oiC
p/
,PPh E ‘ p
Optically active diphenylmenthylphosphine can be conveniently prepared from chlorodiphenylphosphineand the configurationally stable Grignard reagent derived from menthyl chloride.‘? Optically active ferrocenylphosphines are readily obtained by selective lithiation of (6) followed by treatment with a chloro-phosphine. A second phosphino-group may be introduced into the other cyclopentadienyl ring by stepwise lithiation (Scheme 1). i,ii,
CHMeNMe,
CHMeNMe,
\CHMeNMe2 Reagents : i, BuLi-EtzO ; ii, PhzPCl; iii, BuLi-TMEDA-EtzO
Scheme 1
From Metallated Phosphines. The red solutions formed by cleavage of phenyl from alkyldiphenyl- and dialkylphenyl-phosphines with excess lithium in THF show detectable e.s.r. spectra (see Chapter 12). The resulting alkylphenyl- or dialkylphosphides can be added to diphenylvinylphosphine to produce unsymmetrical bis(tertiary phosphines) and react with alkyl halides to form dissymmetric tertiary phosphines.1° The corresponding silylphosphine dilithio-derivatives (7) are also alkylated on treatment with methyl chloride.ll
* lo
K. Issleib and W. Bottcher, Z . anorg. Chem., 1974, 406, 178. M. Tanaka and I. Ogata, Bull. Chem. SOC.Japan, 1975,48, 1094. T. Hayashi, K. Yamamoto, and M. Kumada, Tetrahedron Letters, 1974, 4405. S. 0. Grim and R. P. Molenda, Phosphorus, 1974, 4, 189. S. 0. Grim, J. D. Gandio, R. P. Molenda, C . A. Tolman, and J. P. Jesson, J. Amer. Chern. SOC., 1974, 96, 3416. T. E. Snider, D. L. Morris, W. R. Purdum, G. A. Dilbeck, and K. D. Berlin, Org. Prep. Proced. Internat., 1974, 6, 221 (Chern. A h . , 1975, 82, 57 825).
Phosphines and Phosphoniurn Salts
3
The compound (8), which can be obtained in solution from the reaction of lithium dimethylphosphide with aluminium chloride, forms silyl-phosphines, e.g. (9), when treated with silicon halides.12 Trifluorosilylphosphinehas been prepared by the reaction of trifluorosilyl bromide with (10).13 R,SiPH, + 2EhPLi
&SiPL&
R,SiPMe,
(7)
Me,PH
BuLi+
Me,PLi
*IC4*
H,SiBr
LiAl(PM%],
(8)
Me,SnPH, + F,SiBr
KSiPMe, (9)
F,SiPH,
(10) The cyclothiatetraphosphine (11) is obtained in good yield from the reaction of pentaphenylcyclopentaphosphine and ~u1phur.l~ This phosphine is also obtained Ph Phr/"qPh PhP-PPh
+
-
PhrNsLqPh PhP-PPh
S
II
PhP-PPh I
II
I
S\p/S
Ph (12)
from the reaction of dipotassium triphenylcyclotriphosphineand sulphur dichloride, whereas reaction with dichloro-trisulphane produces the novel heterocycle (12).16 Addition of dilithium ethylphosphide or phenylphosphine to phthaloyl chloridels leads to the cyclic phosphines (13). The preparation of a chiral biphosphine ligand (14) from a dioxole ditosylate has been described.17 Derivatives of 2,3-bis(diphenylphosphino)maleic anhydride (15 ) have been prepared from the 2,3-dichloro-compounds with the aid of diphenyl(trimethylsily1)G. Fritz, H. Schaefer, and W. Hoelderich, Z . anorg. Chem., 1974, 407, 266. G. Fritz and H. Schaefer, 2. anorg. Chem., 1974,406, 167. R. Demuth, Z . Naturforsch., 1974, 29b, 43. l4 M. Baudler, Th. Vakratsas, D. Koch, and K. Kipker, Z . anorg. Chem., 1974, 408, 225. l5 M, Baudler, D. Koch, Th. Vakratsas, E. Tolls, and K. Kipker,Z. anorg. Chem., 1975,413, 239. l6 K. Issleib, K. Mohr, arid H. Sonnenschein, Z . anorg. Chem., 1974, 408, 266. l7 R. Stern, D. Comrnereuc, Y. Chauvin, and H. Kagan, Fr. Demande, 2 190 830 (Chem. Abs., 1974, 81, 63 764).
l1
l2 l3
4
Organophosphorus Chemistry
0
CH,OTs
+
Lipph
__t
f c P P hI
LiPPh
0'
PPh
phosphine.ls Similarly, ethylene diphosphines, e.g. (16), can be obtained by treatment of the corresponding dichloro-compound with a lithium ph0~phide.l~
Me,SiPPh,
+
11
X
-
X = 0, S, CH,,orNMe,
Ar,PLi
+
')==("
Cl Ar = p-MeC,H,
H
(15)
Ar2pxn H
PAr,
(16)
The reaction of sodium methylphenylphosphide with (+ )-(R)-1-chloroethylbenzene gave (&)-(&)-methyl-(a-methylbenzy1)phenylphosphine oxide (17) after
oxidation. Determination of optical purity showed that some induced asymmetry had occurred at the phosphorus atom in the initial reaction.20 By Addition of P-H to Olefns. A detailed study of base-catalysed additions of phosphines, containing two P-H bonds, to vinylic phosphorus compounds has 18
19 20
D. Fenske and H. J. Becher, Chem. Ber., 1975, 108, 21 15. N. P. Nesterova, T. Y . Medved, Yu. M. Polikarpov, and M. I. Kabachnik, Zzcest. Akad. Nuuk S.S.S.R., Ser. khim., 1974, 2295 (Chem. Abs., 1975, 82, 43 521). R. A. Naylor and B. J. Walker, J.C.S. Chem. Comm., 1975, 45.
5
Phosphines and Phosphonium Salts
appeared.,l Treatment of primary phosphines with di-isopropyl vinylphosphonate in a 1 : 1 ratio, followed by reduction, gave (18); in the corresponding reaction with methylphosphine only (19) was isolated (Scheme 2). Full experimental details are
II
RPH, + C&=CHP(OPr'),
-@+
\
RPHCH,CH,PH, (18) R = Ph or n-C,H,, MeP(CH,CH, PH,), (19)
Reagents: i, ButOK; ii, LiAlHa
Scheme 2
now available,, for the preparation of methylated poly(tertiary phosphines) by the conversion of a P-H bond into a PCH,CH,PNe, unit using dimethylvinylphosphine sulphide. Two isomers of (20) with widely differing physical properties are obtained from the base-catalysed addition of (21) to diphenylvinylpho~phine.~~
(Ph,PCH,CH,), PCH,C, KCH, P(CH,CH,PPh,), (22)
The sexidentate ligand (22) has been prepared by reduction of the ester (23) followed by condensation with diphenylvinylphosphine in THF,24and synthesis of poly(tertiary phosphines) with 5, 7, 8, and 10 P atoms has been described.25 Secondary phosphines have been added to formaldehyde t-butylimine to give
aminomethyl-phosphines.26 Bicyclic phosphines such as (24) or (25) have been prepared by treating alkylphosphines with equimolar amounts of cyclo-octadienes in the presence of a freeradical catalyst.27 21 22
23 24
25
2B
R. B. King and J. C. Cloyd, J. Amer. Chem. Soc., 1975,97, 46. R. B. King and J. C. Cloyd, J. Amer. Chem. SOC.,1975, 97, 53. R. B. King, P. R. Heckley, and J. C. Cloyd, 2. Naturforsch., 1974, 29b, 574. M. M. T. Khan and A. E. Martell, Inorg. Chem., 1975, 14, 676. R. B. King and J. C. Cloyd, Phosphorus, 1974, 3, 213. K. Issleib, M. Lischewski, and A. Zschunke, 2. Chem., 1974, 14, 243 (Chern. A h . , 1974, 81, 91 653).
27
B. V. Maatschappij, Neth. Appl., 1973, 12 880 (Chem. A h . , 1974, 80, 146 299).
0rganophosphor us Chemistry
6
(24)
(25)
R = H, Ph,orMe(CHJ,,
By Reduction. Chiral amino-alanes have been used in the asymmetric reduction of racemic 3-methyl-1-phenyl-A2-phospholen1-oxide (26) * and methylphenyl-npropylphosphine oxide. The sign of rotation of the phosphine from reduction of (26) varies, depending upon the reaction conditions.2D
-
R*
I
HN-*l)
I
(--J Ph
H [a]:s =
H
R* = Ph-C-
- 32.1'
to +14.6'
I* I
Me Trichlorosilane can be used to reduce selectively the phosphine oxide bond in the presence of a keto-group (27)30or an ester group (28).31
0
The chiral diphosphine (29), an excellent ligand for use in asymmetric hydrogenation with rhodium catalysts, has been made by reduction of the corresponding
(29) 28 29
30
31
The product derived from the condensation of dichlorophenylphosphine with isoprene is as shown. See L. D. Quin, J. P. Gratz, and T. P. Barket, J . Org. Chem., 1964, 33, 1034. E. Cernia, G. M. Giongo, F. Marcati, and N. Palladino, Inorg. Chim. Acta, 1974, 11, 195. Y . Segall, I. Granoth, and A. Kalir, J.C.S. Chem. Comm., 1974, 501. I. G . Malakhova, E. N. Tsvetkov, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1974, 23, 1761.
Phosphines and Phosphonium Salts
7
diphosphine Higher yields and less meso-(29) were obtained using tributylamine with trichlorosilane rather than the more commonly used triethylamine. Reoxidation with hydrogen peroxide established that inversion had occurred at both phosphorus atoms during the silane reduction. Miscellaneous. A monophosphorus analogue (30) of HMT has been isolated from the reaction of tris(hydroxymethy1)phosphine with HMT in the presence of formalin.3334 Similar treatment of tris(hydroxymethy1)phosphine with cyanamide in the presence of formalin gives (31).36
rr.?
NCN-N~NCN
The reaction of di-isopropyl polymethylenediphosphinates with polymethylene dibromides in the presence of Red-a1 at high dilution gives cis- and trans- macrocyclic diphosphine oxides, which can be reduced to the corresponding cyclic diphosphines (32) using trichlorosilane in benzene.36
n = 9,10, or 12 = 80rlO
VI
Primary and secondary phosphines react with dialkylaminomethyl-phosphines, causing P-C bond cleavage and resulting in the formation of P-P Thus (33) and diphenylphosphine yield tetraphenyldiphosphine,whereas phenylphosphine gives pentaphenylcyclopentaphosphine and (34). Phosphine, when passed through an electric discharge, yields as much as 50% of diphosphine. Methylphosphine gave a mixture of products, among which methyldiphosphine and 1,2-dirnethyldiphosphinecould be identified. A discharge through a 32 33 34 35
36 37
W. S. Knowles, M. J. Sabacky, B. D. Vineyard, and D. J. Weinkauff, J. Amer. Chem. SOC.,1975, 97, 2567. D. J. Daigle and A. B. Pepperman, U.S.P. 391 189 (Chem. A h . , 1974, 81, 120 788). D. J. Daigle and A. B. Pepperman, J. Heterocyclic Chem., 1974, 11, 407. D. J. Daigle, A. B. Pepperman, and F. L. Normand, U.S.P. 374 584 (Chern. A h . , 1974, 81, 120 786). T. H. Chan and B. S. Ong, J. Org. Chern., 1974, 39, 1748. W. C. Kaska and L. Maier, Helv. Chim. Acta, 1974, 57, 2550.
Organophosphorus Chemistry
8
Ph,PCH,NEt, + PhPH
150°C+
Ph,P-PPh,
(33) Ph /p\ PhP PPh Phb-bPh
(33) + PhPH,
+
PhPOcH^ PPh Phh-PPh I
mixture of acetylene and phosphine produces reasonable quantities of ethynylpho~phine.~~ Reactions.-Nucleophilic Attack at Carbon. Carbonyls. The condensation of oaminobenzylphosphine with aldehydes and ketones gives substituted tetrahydro-1,3benzazaphosphorines (35).3 Substituted perhydro-1,3,5-oxazaphosphorines (36)
+
o=c R ''
R' = H or Me R2 = H, Et, or Ph
(35)
- AOAm Ph
PhPH,
+
PhCHO
+ PhCH=NR
PhPANR
Ph
RPH(CH,),PHR
+ 2PhCHO
(37) R = &tor Ph
-
(36)
RP(CH2XPR
I
I
CHOH CHOH
I
Ph
0
0
I
I
It II RP(CHZ),PR CKPh CKPh
I
ph
have been prepared by cyclization of phenylphosphine with benzaldehyde and imine~.~O However, the interaction of diphosphines of the type (37) with benzaldehyde does not give cyclic products but leads to (hydroxyalky1)-phosphines,which rearrange to phosphine The reaction of diphenylphosphine with carbonyl compounds has been reexamined.42The products of these reactions, the a-hydroxyalkyldiphenylphosphines (38), arise from nucleophilic attack at carbonyl carbon followed by proton transfer.
39
J. P. Albrand, S. P. Anderson, H. Goldwhite, and L. Huff, Inorg. Chem., 1975, 14, 570. K. Issleib, H. Winkelmann, and H.-P. Abicht, Synrh. React. Inorg. Met.-Org. Chem., 1974, 4,
40
H. Oehme, K. Issleib, E. Leissring, and A. Zschunke, Synth. React. Inorg. Met.-Org. Chern.,
I1
K. Issleib, H. Oehme, and D. Wineback, J. Organometallic Chem., 1974, 76, 345. E. Evangelidou-Tsolis, F. Ramirez, J. F. Pilot, and C. P. Smith, Phosphorus, 1974, 4, 109.
S8
191. 1974, 4, 453. 42
Phosphines and Phosphonium Salts
9
The corresponding reaction with tertiary phosphines leads to products containing a P - 4 - C bond, which are thought to arise from rearrangement of the initial P-C-0 adducts. Tertiary phosphines have been shown to catalyse the isomerization of a-hydroxy-phosphines 43 Pentafluorobenzaldehyde reacts rapidly with tris(dimethy1amino)phosphine(TDAP), giving a mixture of diastereomeric stilbene oxides (39).44 Miscellaneous.Edge participation of the cyclobutene ring of the non-classical ion (40) is indicated in its reaction with triphenylphosphine, which yields only a product with the substituent in the anti-position to the cyclobutene moiety.45
(40)
1,4Thiaphosphorins (41) have been obtained by addition of phenylphosphine to di-l-alkynyl sulphides in the presence of lithium a i d e in liquid ammonia.4s Alkylbis(hydroxymethy1)phosphines (42) can be converted into (hydroxyethy1)phosphine derivatives by treatment with ethylene oxide.47
R = H,Me,orEt /O\
RP(CH,OH), + C&-CH, (42) R = alkyl 43
44 45
-
(41)
RP(CH,CH,OH),
E. Evangelidou-Tsolis and F. Ramirez, Phosphorus, 1974, 4, 121. R. Filler and Y. S. Rao, J. Org. Chem., 1974, 39, 3421. P. Schipper, P. B. J. Driessen, J. W. de Haan, and H. M. Buck, J. Amer. Chem. Soc., 1974, 96, 4706.
46
47
M. Schoufs, J. Meijer, P. Vermeer, and L. Brandsma, Rec. Trau. chim., 1974, 93, 241. R. K. Valetdinov and S. I. Zaripov, Zhur. obshchei Khim., 1974,44, 1440 (Chem. A h . , 1974,81, 91 637).
10
Organophosphorus Chemistry
Nucleophilic Attack at Halogen. A review of the reactions of tervalent phosphorus compounds with tetrahalogenomethanes and the reactions of the compounds obtained has appeared.48A detailed examination of the influence of the nature of the phosphine, solvent, temperature, and of excess phosphine on the course of the reaction of phosphines with carbon tetrachloride in the presence of acidic nucleophiles has been carried Several reports of the isolation of phosphonium salts from such reactions have been published this year. The aminophosphonium salts (43), formed from the reaction of optically active methylphenyl-n-propylphosphine,carbon tetrachloride, and amines, are optically inactive.50Racemization does not occur via amine exchange but probably arises from (+)-MePrPhP
+ CCl, + R'R'NH + (It)-MePrPhk--NR1R2
c1-
R' = M e , E t , o r H ;
R2 = Bu,Me, or Ph R,P
R
+ CCd + ArXH
.= PhorMe,N;
X = OorS
(43)
R,$--Xk
c1(44)
permutational isomerization of a pentaco-ordinate intermediate. These aminophosphonium salts can be used for the conversion of alcohols into secondary and tertiary amines under mild condition^.^^ (Ary1oxy)- and (ary1thio)-phosphonium salts (44) can be obtained by the simultaneous action of phosphines and carbon tetrachloride on phenols or t h i o p h e n ~ l s53. ~ ~ ~ Alkoxyphosphonium salts derived from the action of TDAP and carbon tetrachloride on diols 64 and secondary alcohols56 have been isolated. N-Chlorodi-isopropylamine can be substituted for carbon tetrachloride in these reactions.55The action of TDAP and carbon tetrachloride on the hydroxybenzotriazole (45) leads to an alkoxyphosphonium salt which is a very effective agent for peptide-coupling reactions, in which there is little racemi~ation.~~ The use of the phosphinexarbon tetrachloride system for the conversion of alcohols into alkyl chlorides has been modified5' by the use of a polystyryl-diphenylphosphine resin as the phosphorus reagent, enabling a simple filtration and evaporation process for product isolation. Oximes give imidoyl chlorides (46) 6 8 or a r n i d e ~via~ Beckmann ~ rearrangements, and N'-benzoyl-N-arylhydrazines (47) are converted into hydrazonyl chlorides,60 using triphenylphosphinewith carbon tetrachloride. H. Teichmann, 2.Chem., 1974,14, 216 (Chem. A h . , 1974, 81,91 602). R. Appel and K. Warning, Chem. Ber., 1975, 108, 606. 5 0 R. Appel and K. Warning, Phosphorus, 1974, 4, 29. 51 Y . Tanigawa, S.-I. Murahashi, and I. Moritani, Tetrahedron Letters, 1975, 471 52 R. Appel, K. Warning, and K. D. Ziehn, Annalen, 1975, 406. 53 H. Teichmann and W. Gerhard, Z . Chem., 1974,14, 233 (Chem. Abs., 1974, 81, 91 652). 54 B, Castro and C. Selve, Bull. SOC.chim. France, 1974, 3004. 55 B. Castro, Y. Chapleur, and B. Gross, Tetrahedron Letters, 1974, 2313. 5~7 B. Castro, J. R. Dormoy, C. Evin, and C . Selve, Tetrahedron Letters, 1975, 1219. 5 7 S. L. Regen and D. P. Lee, J . Org. Chem., 1975, 40, 1669. 5 8 R. Appel and K. Warning, Chem. Ber., 1975, 108, 1437. 59 R. M. Waters, N. Wakabayashi, and E. S. Fields, Org. Prep. Proced. Internat., 1974, 6, 53. 60 P. Wolkoff, Canad. J. Chem., 1975, 53, 1333.
48
49
Phosphines and Phosphonium Salts
11
OH
O;(NM~,),
I
,dp
(Me,N),P +
I
+
cc4 c1-
Oh(NMe,),
I
R
R
\c=NoH
/
w-4=_ Ph,PO
+ CHC1, +
Ph
'C=NPh
I
c1 R = PhorEt
(46)
PhCONHNRAr
PhC-NNRAr
(47) R = HorMe
I
c1
Diphosphines (48) are cleaved by carbon tetrachloride, in a reaction which is reversible at temperatures of up to 100 "C, leading to mixtures of chlorophosphines and (trichloromethy1)phosphines. Isocyanates and dihalogenophosphines can be obtained from the reaction of carbamoyl halides (49) with triphenylphosphine carbon tetrachloride.82Fluorophosphoranes have been synthesized 63 by the reaction
RNHCOX
ph3p-ccL t
RNCO + Ph,PX, + CHCl,
(49) R = Ph or alkyl
of phosphines and chlorophosphines with carbon tetrachloride and HF donors (see Chapter 2). Phosphinic acids react with triphenylphosphine-carbon tetrachloride to give the corresponding acid chloride or anhydride.64Only the anhydrides are formed in the presence of triethylamine but in the presence of primary or secondary amines the acids are converted directly into the corresponding amides (50).85Primary amides R. R. R. e4 R. 65 R. 62 63
Appel and R. Milker, Chem. Ber., 1975, 108, 1783. Appel, K. Warning, D. K. Ziehn, and A. Gilak, Cliem. Ber., 1974, 107, 2671. Appel and A. Gilak, Chem. Ber., 1974, 107, 2169. Appel and H. Einig, 2. anorg. Chem., 1975, 414, 236. Appel and H. Einig, Z . anorg. Chem., 1975, 414, 241.
12
Organophosphorus Chemistry
can react further with triphenylphosphine-carbon tetrachloride,s6 yielding imides (51). In some cases phosphazenes are produced as dehydration products (see Chapter 9). %P(O)(OH) + 2R2R3NH
GP(0)NR2R3
Ph3P-CC4+
(5 0)
&P(O)NH,
+ Ph,P + CCl,
Et3N :
qPN=PPh,
II
0
R* = Me, Ph, OEt, or OPh;
(5 1)
R2 = H o r M e ; R3 = P h o r M e
The use of TDAP and carbon tetrachloride as an activating system for the nucleophilic substitution of alcohols continues to be developed. The intermediate alkoxyphosphonium chlorides (Scheme 3) are usually converted into a more stable salt such R1R2CHOH + (Me,N),P + CCI,
-+ R1R2C€10;(NMe,),
c1-
(Me,N),PO +- R'RTHX
,x-
R1R2CHO$(NMe,), PF,'
Scheme 3
as hexafluorophosphate and then treated with a nucleophile. Activation of a single hydroxy-group of propane-l,3-diols is possible. Selective activation of various positions in carbohydrate derivatives has been 6 9 and the ability of the system to activate alcohols and then enable substitution without rearrangement has been exploited in the synthesis of aryl alkyl ethers and thioethers free from isomers.7o (See also Ref. 76.) A new route to 2,3-dialkylthiiren 1,l-dioxides is provided 71 by the reaction of the tetrabromosulphones (52) with triphenylphosphine in dichloromethane at - 40 "C. However, phosphines open the 2,3-diphenyl analogues at room temperature to give quantitative yields of the betaines (53).72
R RCBr, SO,CBr,R
(52) R = M e o r E t
66
67 68
G9
70 71 72
*
Ph3p
R
7 S 0 2
Ph
Ph
-+ R,P --+
0,
' l S g
Ph
Ph
(53) R = Ph, Me2N, or Et
R. Appel and H. Einig, Chem. Ber., 1975, 108, 914. B. Castro and C. Selve, Bull. SOC.chim. France, 1974, 3009. B. Castro, Y. Chapleur, and B. Gross, Carbohydrate Res., 1974, 36, 412. R. A. Boigograin, B. Castro, and B. Gross, Bull. SOC.chim. France, 1974, 2623. I. M. Downie, H. Heaney, and G . Kemp, Angew. Chem. Internat. Edn., 1975, 14, 370. L. A. Carpino and J. R. Williams, J. Org. Chem., 1974, 39, 2320. B. B. Jarvis and W. P. Tong, Synthesis, 1975, 102.
Phosphines and Phosphonium Salts
13
(54) R = alkyl or phenyl; X = C1 or Br
The reaction of phosphines with a-cyano-a-halogeno-hides of the type (54), and further reactions of the betaine products, continue to be The mechanism of the rapid reduction of a-nitro-bromo-estersto the phosphonium salts (55) with 3 moles of triphenylphosphine has been discussed in some /C02R2 R'CH2C
I
/C02 R2
+
3Ph,P
_.f
R*CH=C
" 0 2
R1 = Ph,Me, or H; R2 = MeorEt
Nucleuphilic Attack at Other Atoms. The reaction of the acyl glycerol (56) with carboxylic acids in the presence of the triphenylphosphine-diethylazodicarboxylate I HO-C-H
I
RC0,H Ph,P-Et02C"NC02Et'
CH,O,CPh
1 H-c02CR
I
CH202CPh
(56)
R = MeorPh
complex causes substitution of the hydroxy-group without concomitant acyloxygroup migration.76 A simple synthesis of alkyl aryl ethers has been described 7 6 involving the reaction between an alcohol and a phenol in the presence of triphenylphosphine-diethyl azodicarboxylate. These reactions occur with inversion of configuration of the alcohol carbon, as shown by the conversion of cholestan-3B-01 into the ether (57). However, the reaction of cholesterol with benzoic acid in the presence of the same reagents 7 7 gives a complex mixture of benzoates which are, at least partially, derived from an intermediate (58) involving C=C participation. Triphenylphosphine appears to be the phosphine of choice for reactions of this type. When monosaccharide derivatives containing isolated hydroxy-groups are treated with equal amounts of TDAP and a dialkyl azodicarboxylate, mixed carbonates (59) are obtained.7 8 Substituted carbohydrates can be converted into the 73 74 75
76 77 78
M. F. Pommeret-Chasle, A. Foucaud, and M. Hassairi, Tetrahedron, 1974,30, 4181. D. Leguern, G. Morel, and A. Foucaud, Bull. SOC.chim. France, 1975, 252. R. Aneja, A. P. Davies, A. Harkes, and J. A. Knaggs, J.C.S. Chem. Comm., 1974, 963. M. S. Manhas, W. H. Hoffman, B. Lal, and A. K. Bose, J.C.S. Perkin I, 1975, 461. R. Aneja, A. P. Davies, and J. A. Knaggs, Tetrahedron Letters, 1975, 1033. G. Grynkiewicz, J. Jurczak, 2nd A. Zamojski, J.C.S. Chem. Comm., 1974, 413.
Organophosphorus Chemistry
14
R'OH + (Me,N),P + R20,CN=NC0,R2
* RIOCO,R' + R10NNHC02R2
I
CO,R2
(59)
expected phthalimide derivatives by diethyl azodicarboxylate-triphenylphosphine in the presence of phthalimide, but when TDAP is used79the main products are (59; R2 = Et)and(60;R2 = Et). The combination of triphenylphosphine and 2,2'-dipyridyl disulphide as a condeosing agent has been shown to be very effective under neutral aprotic conditions. The use of these reagents has been extended to the intramolecular synthesis of
L
0
R = tetrahydropyranyl '0
(61)
J. Jurczak, G. Grynkiewicz, and A. Zamojski, Carbohydrate Res., 1975, 39, 147.
Phosphines and Phosphonium Salts
15
macrocyclic lactones from co-hydroxy-alkanoicacids,80the synthesis of lactones, e.g (61), in the prostaglandin series,81and of complex naturally occurring macrocyclic compounds from hydroxy-acids.82Their use as condensing agents in solid-phase peptide synthesis has also been inve~tigated.~~ A stopped-flow kinetic study of the reaction of triphenylphosphine with aryl disulphides in aqueous dioxan, which affords the corresponding benzenethiol and triphenylphosphine oxide in quantitative yield, has been The authors propose a two-step mechanism for these reactions (Scheme 4). ph,P
* Ph36SR + A r S -
+ ArSSR
Ph3kR
+ KO
-+ Ph,PO Scheme 4
+ ArS-
Selective formation of 5’-S-alkylthio-Y-deoxyribonucleosides (62) can be achieved by the reaction of nucleosides with dialkyl disulphides and tri-n-butylphosphine, CH,OAc
B = nucleoside base; R’ = HorOH;
(63) X = S o r S e S
-1
R2 = 2-pyridyl, Ph, Me, or Et,NC-
even when excess amounts of the phosphine and dialkyl disulphides are used.86The combination of diphenyl disulphide and tri-n-butylphosphine is useful for the introduction of the phenylthio-group onto phosphate residues of nucleotides.8 6 Dimethylphosphinous acid esters of thio- or seleno-sugars (63) have been prepared by the reaction of tetramethyldiphosphine with the carbohydrate disulphide or diselenide.8 7 The o-nitrophenylsulphenyl group can be used for protecting amino-groups of peptides. This group is selectively removed in the presence of benzyloxycarbonyl, benzyl ester, and t-butyl groups, by the use of triphenylphosphine and an activehydrogen compound such as a phenol (Scheme 5).88
83
E. J. Corey and K. C. Nicolaou, J. Amer. Chem. SOC.,1974, 96, 5614. E. J. Corey, K. C. Nicolaou, and L. S. Melvin, J. Amer. Chem. SOC.,1975, 97, 653. E. J. Corey, K. C. Nicolaou, and L. S. Melvin, J . Amer. Chem. SOC.,1975, 97, 654. R. Matsueda, H. Maruyama, E. Kitazawa, H. Takahagi, and T. Mukaiyama, J . Amer. Chem.
84
L. E. Overman, D. Matzinger, E. O’Connor, and J. D. Overman, J. Amer. Chem. SOC.,1974,96,
80
81 82
SOC.,1975, 97, 2573.
608 1. 85 86
87 88
I. Nakagawa and T. Hata, Tetrahedron Letters, 1975, 1409. T. Hata and M. Sekine, Chem. Letters, 1974, 837 (Chem. Abs., 1974, 81, 120 917). C. D. Mickey, P. H. Javora, and R. A. Zingaro, J. Curbohydr., Nucleosides, Nucleotides, 1974,1, 291 (Chem. Abs., 1975, 82, 98 270). Ref. 83, footnote (4).
Organophosphorus Chemistry
16
P1,P
I -OR Scheme 5
Miscellaneous. The treatment of tertiary phosphines with alkyl-lithium reagents may lead to nucleophilic substitution at phosphorus, which can be very competitive with deprotonation depending upon the medium used.8 9 Thus methyldiphenylphosphine gives 1.7 times more substitution of phenyl than deprotonation with n-butyl-lithium in THF. Investigation of the stereochemistry of the substitution reaction shows that, when the phosphine (64) is treated with n-butyl-lithium, substitution of benzyl occurs with complete inversion of configuration, presumably through an intermediate or transition state (65). C H IPh
Me
BU
(69
(64)
The ring size of cyclopolyphosphines in solution may be determined by the multiplicity of the proton-decoupled 31Pn.m.r. signal 91 (see Chapter 12). Using reassigned ring sizes, it has been shown that tetra- and penta-cyclopolyphosphines have electrochemical reduction potentials which are solely dependent upon the pendant organic group and are not affected by ring size.g2 Acylphosphines (66) can be decarbonylated by heating with Wilkinson’s catalyst in ~ y l e n e . ~ ~ RCOPPh,
f
RhCI(PPh,),
-
RPPh,
+ Ph,P
f
RhCI(CO)(PPhJ2
(66)
The P-C bond of phosphines can be cleaved in acidic media if a b-carbonyl group is present, e.g. as in (67).94 89 9O
91
92
g3 94
E. P. Kyba and C. W. Hudson, Tetrahedron Letters, 1975, 1869. E. P. Kyba, J. Amer. Chem. SOC.,1975, 97, 2554. L. R. Smith and J. L. Mills, J.C.S. Chem. Comm., 1974, 808. T. J. DuPont, L. R. Smith, and J. L. Mills, J.C.S. Chem. Comm., 1974, 1001. E. Linder and A. Thasitis, Chem. Ber., 1974, 107, 2418. L. D. Quin and C. E. Roser, J . Org. Chem., 1974, 39, 3423.
Phosphines and Phosphonium Salts
n
17
..-
ke (68)
(67)
The absolute configuration of the phosphine (68) has been determined by chemical correlation with ( + )-(S)-benzylmethylphenylpropylphosphonium bromide.95 2 Phosphonium Salts
Preparation.-Treatment of a variety of tertiary phosphines with allylic halides yields phosphonium salts, which can be cyclized to heterocyclic systems with 115% polyphosphoric acid (pPA),gse.g. as in Scheme 6.
Reagents: i, 115% PPA; ii, HzO; iii, KPFa
Scheme 6
The reaction of tertiary phosphines with bromomethyl-substituted alkynes produces mixtures of acetylenic (69) and allenic (70) phosphonium Salkg7
R,P
+
B~CH,C~CH I_) R , ~ = c M ~+ R , ~ H = C = C H ,
(70)
(69)
R = Ph or Bu
Vinyl 1,2-bistriphenylphosphoniumbromide (71) is an unexpected product of the reaction between triphenylphosphineand the isomeric (bromoviny1)phenylsulphones (72) and (73).g8 PhSO,CH=CHBr
(72) or PhSO,C=CHz
I Br
2Br-
(71)
(73) The salt (71), which has been shown to have the (E)-configurati~n,~~ can be more conveniently prepared from triphenylphosphine with acetyl bromide or acetic 95
96
97 98
99
R. Luckenbach, Annalen, 1974, 1618. G. A. Dilbeck, D. L. Morris, and K. D. Berlin, J. Org. Chem., 1975, 40, 1150. R. A. Khachatryan, A. M. Ovakimyan, and M. G. Indzhikyan, Armyan. khim. Zhur., 1974,27, 682 (Chem. A h . , 1975, 82, 31 379). E. G. Kataev, F. R. Tantasheva, E. A. Berdnikov, and B. Ya.Margulis, Zhur. org. Khim.,1974, 10, 1050 (Chem. Abs., 1974, 81, 78 025). H. Christol, H. J. Cristau, and J. P. Joubert, Bull. SOC.chim. France, 1974, 2975.
0rganophosphorus Chemistry
18
anhydride-hydrogen bromide.loOThese latter reactions are thought to involve acylation, addition, and elimination steps.1012-Substituted vinylphosphonium salts (74) may be obtained directly from (71) by addition of compounds containing acidic +
+
Ph, PCH-CCIiPPh,
+
Et,N
Kli
+
*
Ph3PCH=CI1R
2Br-
Br-
(71)
(74) R = MeO, PIiO, EtS, PhS, or Ph,P
'
OE t
EtOCHRrCH,Br
+
Ph,P --+ [Ph,$!:;H2~j
Et3N=
Ph, P+ -C
B r-
(75)
CH,
Br-
hydrogens in the presence of triethylamine.lo2 The synthesis of l-(ethoxyviny1)triphenylphosphoniumbromide from the dibromide (75) and triphenylphosphine has been described.lo3 Vinylphosphonium salts (76) may be obtained from the reaction of triphenylphosphine with a 2-halogeno-ethanol followed by dehydration.lo4 R,P
+ XCH2CH20H --+ R$?C&CH;OH
__c
%kH=CH,
X' Jl= alkyloraryl
(76)
Tetra-arylphosphonium halides can be prepared lo5by the addition of triphenylphosphine to aryl halides in the presence of catalytic amounts of tris(tripheny1phosphine)nickel(m) (Scheme 7). The synthesis of a number of chiral tetra-arylphosphonium salts via the cobalt-salt method has been reported.los PPh,
I + Ph,P IPPh,
ArX + Ni(PPh3), -+ Ar-Ni--X pfi3
I
Ar-Ni-X
II PPh,
+ 2Ph,P
_3.
ArgPh,
+ Ni(PPh3),
X' Scheme 7
loo H. Christol, H. J. Cristau, and J. P. Joubert, Bull. SOC.chim. France, 1974, 1421. l01 H. Christol, H. J. Cristau, and J. P. Joubert, Bull. SOC.chim. France, 1974, 2263. 102 H. Christol, H. J. Cristau, J. P. Joubert, and M. Soleiman, Compt. rend., 1974, 279, C, 167. l o 3 J. M. McIntosh and H. B. Goodbrand, Synthesis, 1974, 862. 104 M. Grayson and P. T. Keough, U.S.P. 3 836 587 (Chem. Abs., 1975, 82, 31 392). 105 L. Cassar and M. Foa, J. Organometallic Chem., 1974, 74, 75. 106 R. Luckenbach, Tetrahedron Letters, 1975, 1673.
Phosphines and Phosphonium Salts
19
Spirophosphonium chlorides (77) can be isolated in low yielc together with secondary phosphine oxides from the reaction of diaryl-amines and phosphorus tri~hl0ride.l~' The reactions of anilines with phosphorus trichloride and dichlorophosphines have been described.lo8 N-Chloroguanidines react with triphenylphosphine, giving phosphonium salts (78).loQ The useful brominating agent (79) may be preparedl10 by allowing triphenyl-
R
\
R N-CENCl
'
1
+ Ph,P
\
'
NH,
R = MeorPh
N-C=N-;Ph,
I
NH,
Ph,kH,CH,CO,H c1-
Br;
(79)
(78)
phosphine to react with acrylic acid and 49 % aqueous hydrobromic acid, followed by addition of bromine in acetic acid. The addition of (arylmethy1)triphenylphosphonium salts to the acetal(80) leads to phosphonium salts, which on hydrolysis are converted into a-formylated derivatives (81).ll1 Ph,kH,Ar t MeNCH(OEt), -+ Ph,kAr (80)
ll CHNMe,
H +-H,O
~
Ph,kHAr
1
CHO
Reactions.-AZkaline HydvoZysis. The rate of hydrolysis of benzyltriphenylphosphonium bromide in aqueous THF is increased remarkably, by a factor of more than lo6, as the water content of the medium is reduced. The increase is ascribed to a solvent effect.'l2 The basic hydrolysis of vinyl 1,Zbisphosphonium salts, in which the mode of decomposition is determined by base concentration, has been lo7
R. N. Jenkins and L. D. Freedman, J. Org. Chem., 1975, 40, 766. Teichmann, W. Gerhard, and W. Kochmann, East Ger. P. 105 242 (Chem. Abs., 1975,82,
lo8H.
43 042). logA.
Heesing and G. Imsieke, Chem. Ber., 1974, 107, 1536. V. W. Armstrong, N. H. Chishti, and R. Ramage, Tetrahedron Letters, 1975, 373. 111 M. A. Grassberger, Annalen, 1974, 1872. 112 A. Schnell and J. C. Tebby, J.C.S. Chem. Comm., 1975, 134. 113 H. Christol, H. J. Cristeau, and M. Soleiman, Tetrahedron Letters, 1975, 1385. 11O
20
Organophosphorus Chemistry
The expected inversion of configuration at phosphorus is observed114 in the hydrolysis of the phosphocanium salt (82), whereas the salts (83) rapidly ring-open in alkaline solution to give the oxides (84). Reaction with less than one equivalent of base showed epimerization of the unchanged ~ a 1 t . l ~ ~
Me
I
0 a;<. A
PhCH,
NaoH*
Ph
(82)
'Y (83) X = Me; Y = MeorPhCH,
&H
R (84) R = POMe,orPhCH,PMe
II
0
The alkaline hydrolysis of the isomeric iodomethylpentamethylphosphetanium salts (85) and (86) gave different ring-expanded oxides,ll6there being no isomer crossover, unlike the crossover observed in other reactions in this series.
(861 (2-Acetoxyethy1)phosphoniumsalts (87) give (2-hydroxyethy1)phosphonium salts on hydrolysis at pH 8-1 1, by an elimination-addition rea~ti0n.l~' The intermediate (85)
vinylphosphonium salt can be trapped by cyanide ion. This type of reaction is general for phosphonium salts which have a leaving group in the 2 - p o ~ i t i o n . ~ ~ ~ A study of the products of the alkaline hydrolysis of phenyl- and benzylphosphonium salts bearing the l-methylpyrro1-2-y1(88)group shows that the ease of cleavage of the heteroaryl substituent is between that of benzyl and phenyl sub~tituents.~~~ K. L. Marsi and F. B. Burns, Phosphorus, 1974, 4,211. S. E. Gremer, F. R. Farr, P. W. Kremer, H. Hwang, G. A. Gray, and M. G. Newton, J.C.S. Chem. Comm., 1975, 374. 116 H. A. S. My, D. J. H. Smith, and S. Trippett, Phosphorus, 1974, 4, 205. 117 H. Kanz, Phosphorus, 1974, 3, 273. 118 H. Christol, H. J. Cristau, and M. Soleiman, Tetrahedron Letters, 1975, 1381. D. W. Allen, B. G. Hutley, and M. T. J. Mellor, J.C.S. Perkin 11, 1974, 1690.
114 115
21
Phosphines and Phosphonium Salts
Decomposition of phosphonium salts (89) containing 2-propenyl substituents in aqueous base produces mixtures of isomeric alkenes.120, lZ1 R$CH2CH=CHR2 (89) R* = BuorPh; R’ = Me or Ph
-
RiPO + MeCH-CHR’
iCH,=CHCH,R2
Aromatic aldehydes can be obtained by the hydrolysis of the acyl-phosphonium salts (90).lz2 The alkoxide-catalysed cleavage of acyclic phosphonium salts follows the same stereochemicalcourse as the correspondingreaction with aqueous sodium hydroxide, although the stereoselectivity is 10wer.l~~ A kinetic study lZ4of the ethoxide-catalysed decomposition of (3-hydroxypropy1)triphenylphosphoniumchloride indicates the presence of a sexicovalent intermediate or transition state, formed by attack of ethoxide ion on a pentaco-ordinate species (Scheme 8).
6Et Scheme 8
Additions to VinyIphosphoniumSalts. The synthesis of heterocyclic compounds from vinylphosphonium salts has been r e v i e ~ e d126 .~~~~ M. Z.Ovakimyan, R. A. Khachatryan, A. A. Simonyan, and M. G. Indzhikyan, Armyan. khim. Zhur., 1973, 26, 1030 (Chem. Abs., 1973, 81, 13 608). 1 2 1 M. Z.Ovakimyan, R. A. Khachatryan, and M. G. Indzhikyan, Armyun. khim. Zhur., 1974,27, 593 (Chem. Abs., 1974,81, 136 237). lZ2 D.G. Smith and D. J. H. Smith, J.C.S. Chem. Comm., 1975, 459. 123 R. Luckenbach, Chem. Ber., 1975,108, 803. lZ4 G. Aksnes and A. I. Eide, Phosphorus, 1974,4, 209. 125 E. Zbiral, Synthesis, 1974, 775. 126 T.Nishiwaki, Yuki Gosei Kugaku Kyokai Shi, 1974,32,563 (Chem. Abs., 1974,82,4142). 120
2
22
Organophosphorus Chemistry
The diallylphosphonium salt (91), which loses propene on alkaline hydrolysis, as expected, can be isomerized to the dipropenyl salt, which in the presence of dilute sodium hydroxide cyclizes to the oxaphosphonium salt (92; X = O).12' The salts (92; X = S or NMe) can be prepared in similar fashion.128
McCH=CH \+
/ppll?. MeCH=CH
XH,
~
OH-
">j'"'
Me' (92) X = S,O,or NMe
The reaction of vinylphosphonium salts with the enolate anions (93) affords cyclopentenone derivatives via an intramolecular Wittig r e a ~ t i 0 n . lThe ~ ~ addition of enolates to trans-l-butadienyltriphenylphosphonium bromide (94), giving cyclohexa-l,3-dienes, has also been described.130
R'
R1 = H or alkyl; Rz = R3 = H or Me
R' = H, Me, or Ph; Rz = H o r M e ; R3 = H,Ph,orCOMe
3-Phenyl-2H-azirines react with triphenylvinylphosphonium bromide in the presence of light to form 2H-indoles dire~t1y.l~~ The reaction presumably proceeds via the photochemically generated dipolar species (Scheme 9). The predominance of the cis-isomer in the formation of the dihydrothiophens (95) from vinylphosphonium salts and a-mercaptocarbonylcompounds has been ascribed to a steric effect.132 127 128 129 130 131 132
L. Horner and S. Sanaan, Phosphorus, 1974, 4, 1. S. Samaan, Tetrahedron Letters, 1974, 3927. I. Kawamoto, S. Muramatsu, and Y. Yura, Tetrahedron Letters, 1974, 4223. P. L. Fuchs, Tetrahedron Letters, 1974, 4055. N. Gakis, H. Heimgartner, and H. Schmid, Helv. Chim. Acta, 1974, 57, 1403. J. M. McIntosh and G . M. Masse, J. Org. Chem., 1975, 40, 1294.
Phosphines and Phosphonium Salts
23
Scheme 9
R2 +
R'
lJ==A R3y
R3 + Ph,PO
R'
Triphenyl(prop-2-yny1)phosphonium bromide has been used to prepare intermediates (96), which are useful for the synthesis of a variety of heterocycles133 using an ylide-extrusion reaction, e.g. Scheme 10. 0
II
HC=CCH,
+
PPh,
+
Me
PPh,
Scheme 10
Transformations of nucleoside bases with /I-acylvinylphosphoniumsalts continue to be Miscellaneous.-The reaction of the salt (97) in refluxing ethanolic sodium ethoxide gave a mixture of the expected benzoxocin (98) together with 2-ethyl-2H-1-benzopyran and a phosphine oxide (98a). Multi-step mechanisms are proposed for the formation of the latter two 133 134 135
E. E. Schweizer and S. V. Devoe, J. Org. Chem., 1975, 40, 144. C. Ivancsics and E. Zbiral, Monafsh., 1975, 106, 417.
E. E. Schweizer, T. Minami, and S. E. Anderson, J. Org. Chem., 1974, 39, 3038.
24
Organophosphorus Chemistry
(984 The optical purity of optically active phosphonium salts can be determined by differential scanning The electronic structures of vinylphosphonium phosphonium salts containing other unsaturated groups,138and alkyltriphenylphosphonium salts139 have been investigated using lSCand 31Pn.m.r.
3 Phospholes The synthesis and some reactions of the novel aromatic heterocycles (99) and (100) have been described.140 The reaction of aza-compounds with phosphorus trichloride produces the related compounds (101).141
R"=NCH2CH2R2
t. PCb
-+
R"-N
\\
/
+ 3HC1
I
RZ (101) Tris(hydroxymethy1)phosphine reacts with the di-yne (102) to give the diphosphole derivative (103) via a phosphole dipole intermediate.142 Reactions of P-substituted phospholes with an alkali metal always result in cleavage of the exocycliccarbon-phosphorus bond, forming a phosphide anion and a carbanion.143 136
R. Luckenbach and L. Horner, Thermochim. Acta, 1975, 11, 216 (Chem. Abs., 1975, 82, 98 064).
13'
T. A. Albright, S. V. Devoe, W. J. Freeman, and E. E. Schweizer, J. Org. Chem., 1975, 40,
13* 139
T. A. Albright, W. J. Freeman, and E. E. Schweizer, J. Amer. Chem. SOC.,1975, 97,2946. T. A. Albright, W. J. Freeman, and E. E. Schweizer, J. Amer. Chem. Suc., 1975, 97, 2942. Y.Charbonnel and J. Barrans, Compt. rend., 1974, 278, C, 355. L. Dulog, F. Nierlich, and A. Verhelst, Phosphorus, 1974, 4, 197. G. Miirkl, H. Hauptmann, and F. Lieb, Phosphorus, 1974, 4, 279. L. D. Freedman, B. R. Ezzell, R. N. Jenkins, and R. M. Harris, Phosphorus, 1974,4, 199.
1651.
141 143
143
25
Phosphines and Phosphoniurn Salts H
"XoH
4 % Ph/
+ P(CH,OH),
'Ph
1,2,5-Triphenylphospholeand l-diazonaphthen-2-onegive an ylide (104), which at The synthesis of benzofurazans using the 175 "Cforms 7,lO-diphenyIfl~oranthene.~~~ reaction of azides with 1,2,5-triphenylphospholehas been described in detail.145
Full papers discussing the reaction of l-phenyl-3,4-dimethylphospholewith aromatic acid chlorides followed by treatment with water,146and the generation and have appeared. reaction of the anion (105) with carbonyl
Additional evidence that electronic delocalization in phospholes is small has been obtained from the rates of quaternization of, and polarographic studies on, 5phenylbenzoph~sphole,~~~ and from magnetic molecular rotations (Faraday effect) of l-butylphosphole.149 The lower barrier to pyramidal inversion of phosphorus in phospholes compared to simple phosphines has been discussed in terms of a more effective electron delocalization in the planar transition state compared to the ground state.160 This point is borne out by theoretical studies on the ground state and the planar transition 144
145 146 147 148 1-19 150
J. I. G. Cadogan, R. J. Scott, and N. H. Wilson, J.C.S. Chem. Comm., 1974, 902. J. I. G. Cadogan, R. J. Scott, R. D. Gee, and I. Gosney, J.C.S. Perkin I, 1974, 1694. F. Mathey, D. Thavard, and B. Bartet, Canad. J. Chem., 1975, 53, 855. F. Mathey, Tetrahedron, 1974, 30, 3127. D. W. Allen, J. R. Charlton, B. G. Hutley, and L. C. Middleton, Phosphorus, 1974, 5, 9. M. F. Bruniquel, J. F. Labarre, and F. Mathey, Phosphorus, 1974, 3, 269. J. D. Andose, A. Rauk, and K. Mislow, J. Amer. Chem. Soc., 1974, 96, 6904.
26
Organophosphorus Chemistry
state of phospholes ;the studies indicate that 2pn-3pn conjugation increases with the planarity of the These results may explain the conflicting experimental and theoretical studies on the electronic delocalization in phosphole rings. 4 Phosphorins
Preparation.-A review of compounds containing a P - C n-bond has been p~b1ished.l~~ The addition of dibutyltin dihydride to substituted 1 ,4-di-ynes gives a mixture of 1 : 1 adducts. The six-membered-ring adduct may be converted, without prior separation, into the phosphabenzeneby treatment with phosphorus tribromide (Scheme 11).
Reagents: i, BuaSnHz; ii, PBr3
Scheme 11
However, this method of preparation has severe limitations; as the amount of substitution of the di-yne increases so does the amount of five-membered-ring adduct.lS3 Trichlorosilanereduction of the phosphacyclohexenones(106) followed by distillation gave 3-arylphosphabenzenes(Scheme 12).164 Phosphatriptycenecan be prepared by cyclizing (107) with an excess of lithium di-is~propylamide.~~~
Reagents: i, ClsSiH; ii, A
Scheme 12
Full details of the preparation of 2-phosphanaphthalenes have appeared.16s
151
G.Kaufmann and F. Mathey, Phosphorus, 1974, 4, 231.
152
P. Jutzi, Angew. Chem. Internat. Edn., 1975, 14, 232.
153 l54 155
A. J. Ashe, W.-T. Chan, and E. Perozzi, Tetrahedron Letters, 1975, 1083. G. Mark1 and D. Matthes, Tetrahedron Letters, 1974,4381. C. Jongsma, J. P. Dekleijn, and F. Bickelhaupt, Tetrahedron, 1974, 30, 3456. H. G. Graaf and F. Bickelhaupt, Tetrahedron, 1975, 31. 1097.
l56
Phosphines and Phosphonium Salts
27
Reactions.-The syntheses of phosphorins having aldehyde and cyano-,16' acetyland unsaturated groups159at C-4 have been described. The reaction of 2-phenyl-1-phosphanaphthalenewith Grignard reagents affords an anion which forms (108; R2 = H or PhCH2) on treatment with protons or benzyl bromide, respective1y.ls0
\
p/ Ph.
+
R'MgBr
I
I
R'
R'
R' = Ph or But;
R'
(108)
= H or PhCH,
The anions obtained by the reaction of 2,4,6-triphenylphosphabenzenewith organo-lithium reagents give the interesting n-complexes (109) when added to ferrous chloride in THF.lsl
0 - fi
Ph\p
Ph
+ MeLi
Ph
y Ph
F&4+ THF
Me Ph
The gold(1) chloride complex of 2,4,6-triphenylphosphorincan be converted into a crystalline compound, described as a Au, cluster,ls2by addition of sodium methoxide. 2-Phenyl-1-phosphanaphthalene undergoes cycloaddition reactionsls3 with alkynes and benzyne to give benzophosphabarralene derivatives, a.g. (1 10).
Kinetic and thermodynamic data, together with the regio- and stereo-specific nature of the reaction, indicate that the thermal conversion of 1-acetoxyphosphorins H. H. Pohl and K. Dimroth, Angew. Chem. Internat. Edn., 1975, 14, 111. K. Dimroth and M. Luckoff, Angew. Chem. Internat. Edn., 1975, 14, 112. 159 H. H. Pohl and K. Dimroth, Chem. Ber., 1975, 108, 1384. 160 G. Markl and K. H. Heier, Tetrahedron Letters, 1974, 4501. 161 G. Markl and C. Martin, Angew. Chem. Internat. Edn., 1974, 13, 408. H. Kanter and K. Dimroth, Tetrahedron Letters, 1975, 545. G . Mgrkl and K. H. Heier, Tetrahedron Letters, 1974. 4369. 15'
28
Organophosphorus Chemistry
(1 1 1) into phosphacyclohexadiene derivatives involves a 1,3- or 1,7-sigmatropic rearrangement.lB4The phosphorin (1 12) thermally rearranges to (1 13), which undergoes a 3,3-sigmatropic rearrangement on further heating in toluene. An intramolecular Diels-Alder reaction occurs on even longer heating in toluene, to give a CH=CD,
Ph&Ph
/ NoCD2CH=CH2
Me
tricyclic compound whose structure is unknown.16s A detectable e.s.r. signal in a warmed solution of (1 12) in toluene indicates that the rearrangement to (1 13) is not synchronous. The crystal structure of 2-phenyl-l-phosphanaphthaleneshows that the phosphanaphthalene group is nearly planar, and that bond-length variations are characteristic of a naphthalene system.lG6The analysis of electron-diffraction and microwave data for phosphabenzene suggests that it is aromatic, with small but significant involvement of phosphorus d-orbitals in the n-bonding.ls7 The electronic structure of phosphorins has been probed using 13Cn.m.r.lS8(See Chapter 12.)
164
165 166 167
16*
M. Constenla and K. Dimroth, Chem. Ber., 1974, 107, 3501. 0. Schaffer and K. Dimroth, Angew. Chem. Internat. Edn., 1975, 14, 112. J. J. Daly and F. Sanz, J.C.S. Dalton, 1974, 2388. T. C. Wong and L. S. Bartell, J. Chem. Phys., 1974, 61, 2840. T. Bundgaard, H. J. Jakobsen, K. Dimroth, and H. H. Pohl, Tetrahedron Letters, 1974, 3179.
2 Q u inq uecovalent Phosphorus Corn pou nds BY S. TRIPPETT
1 Introduction Cyclic oxyphosphoranes have been reviewed.l The conformational preferences of spirocyclic phosphoranes have been discussed2in the light of recent X-ray analyses showing square-pyramidal geometry in some cases.3 The trend to square-pyramidal geometry in spirophosphoranes containing highly electronegative groups attached to phosphorus leads to reduced ring strain and better electronic balance. Existing
(3)
(4)
dynamic n.m.r. data cannot distinguish between square-pyramidal and trigonalbipyramidal geometry. However, this year’s crop of X-ray analyses has revealed only ‘essentially’ or ‘distorted’ trigonal-bipyramidal structures in the phosphoranes (1),4 (2),6 (3),6 and (4).’ The nitrogens in (3) and (4) are planar.
3
5
7
B. A. Arbuzov and N . A. Polezhaeva, Uspekhi Khim., 1974,43,933. R . R . Holmes, J. Amer. Chem. SOC.,1974, 96, 4143. ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1975, vol. 6, p. 27. E. Duff, D. R. Russell, and S. Trippett, Phosphorus, 1974, 4, 203. H. L. Carrell, H. M. Berman, J. S. Ricci, jun., W. C. Hamilton, F. Ramirez, J. F. Marecek, L. Kramer, and I. Ugi, J. Amer. Chem. Soc., 1975, 97, 38. M. G. Newton, J. E. Collier, and R. Wolf, J. Amer. Chem. Soc., 1974, 96, 6888. A. E. Kalinin, V. G. Andrianov, and Yu. T. Struchkov, Zhur. strukt. Khim., 1974, 15, 1132.
Organophosphorus Chemistry
30 2 Acyclic Systems
Ab initio calculations have been reported on PF5 and PF4H.s Fluorophosphoranes have been prepared from chlorophosphines as shown in Scheme 1. The best HF-donor is phenylcarbamoyl fluoride. Among other fluoroR,-,PCl,
+ CCI, + (n + 2)HF,D
__f
R,-,PF,+,
+ CHC1, +
(12
+l)HCI,D
+
D
D = KI:, NH,, Et,N, or PhNCO
ex. Bu: PF, (72%), PhMePF, (73%) Scheme 1
phosphoranes described are C,F,PRF, (R = Me, But, or Ph)lo and the diphosphoranes (5).11 R,P(:NSiMe,) (CH,),P(:NSiMe,)R,
R,PF, (CH,),PF,R2 (5 1
n = 1 , 2 , o r 3; R = Meor Ph
Further examples of non-equivalent apical fluorines have been observedla in the low-temperature19Fn.m.r. spectra of fluorophosphoraneswhen the non-equivalence is due to one, two, or three identical or different asymmetric alkyl or alkoxy-groups. Application of the different ' J F Pcoupling constants to apical and equatorial CF, groups to establish the stable conformations at low temperatures of trifluoromethylphosphoranes has been extended l3 to a study of the phosphoranes (CF3),P(NMe2),, (CF,),PCI(NMe,), (CF3)2PX(NMe,), (X = F or Cl), (CF3)2PCl,(NMe,), CF,PF,(NMe,),, and Me(CF,),PX (X = F, CI, or OMe). The results are in agreement with the order of apicophilicity F, C1> CF, > NMe,, OMe. The 13Cn.m.r. spectrum of Me4POMeat - 90 "C shows separate signals for apical The variableand equatorial methyls, with J P C 7.3 and 116 Hz, re~pective1y.l~ temperature n.m.r. spectra of the tetrafluorophosphoranes FIPX (X = C1, Me, NMe2,15and NPr', 16)have been described and the variable-temperature l9F n.m.r. spectrum of MeSPF, has been simulated by computer to explain apparent anomalies in the experimental spectrum.17
3 Four-membered Rings Treatment of the phosphonium salt (6) with methyl-lithium gavelS the salt (7), J. M. Howell, J. R. Van Wazer, and A. R. Rossi, Inorg. Chem., 1974, 13, 1747. R. Appel and A. Gilak, Chem. Ber., 1974,107, 2169. M. Fild and T. Stankiewicz, Z . unorg. Chem., 1974, 406, 115. l1 R. Appel and I. Ruppert, Chem. Ber., 1975, 108, 919. l a D. U. Robert, D. J. Costa, and J. G. Riess, J.C.S. Chem. Comm., 1975, 29. 13 K. I. The and R. G. Cavell, J.C.S. Chem. Comm., 1975, 279; D. D. Poulin and R. G. Cavell, I w r g . Chem., 1974, 13, 2324, 3012. l4 H. Schmidbaur, W. Buchner, and F. H. Kohler, J. Amer. Chem. Soc., 1974,96, 6208. l 5 M. Eisenhut, H. L. Mitchell, D. D. Traficante, R. J. Kaufman, J. M. Deutch, and G . M. Whitesides, J. Amer. Chem. SOC., 1974, 96, 5385. l6 A. H. Cowley, R. W. Braun, and J. W. Gilje, J. Amer. Chem. SOC.,1975, 97, 434. l7 R. B. Johannesen, S. C. Peake, and R. Schmutzler, 2.Nuturforsch., 1974, 29b, 699. lS S. E. Cremer, F. R. Farr, P. W. Kremer, H.-0. Hwang, G. A. Gray, and M. G. Newton, J.C.S. Chem. Comm., 1975, 374. 8
9 10
Quinquecoualent Phosphorus Compounds
31
norbornadiene (10 %), and trimethylphosphine (10 %), presumably via the fourmembered phosphorane (8). The 1,2-0xaphosphetans(10)have been obtained19both from the corresponding phosphines and hexafluoroacetone and from the alkoxyphosphonium salts (9) as shown. CH,R
Ph,PH
-t (CF,),CO
* Ph,PC(OI-I) (CF,),
RCH,X
+/
5
Ph,P
X-
\
OCH(CF,>,
(9 1
.1
R,N (CF,),CO
(10)
1,3,2,4-Diazadiphosphetidineshave been obtained from pyrolysis of the difluorophosphorane (1 1)2o and starting from acid hydrazides,21as shown in Scheme 2. Both
R'CONHNHR2 + X,PCl, Me or Ph
d
X = C1, Me,or Ph
H or Ph
-.
R2 R'
Reagents: i, Et3N
Scheme 2
(1 1) and (12) show temperature-dependent sets of trifluoromethyl groups in their lQFn.m.r. spectra. The products previously obtained from o-aminophenol and trichlorophosphoranes have now 22 been shown to be diazadiphosphetidines,e.g. (4) from trichlorodiethylphosphorane. ' 9
l9 2o
21 22
E. Evangelidou-Tsolis and F. Ramirez, Phosphorus, 1974, 4, 121. J. A. Gibson and G.-V. Roschenthaler, J.C.S. Chem. Comm., 1974, 694. A. Schmidpeter and J. Luber, Chem. Ber., 1975, 108, 820. A. Schmidpeter and J. Luber, Phosphorus, 1974,5,55; M. I. Kabachnik, V. A. Gilyarov, N. A. Tikhonina, A. E. Kalinin, V. G. Andrianov, Yu. T. Struchkov, and G. I. Timofeeva, ibid., p. 65.
Organophosphorus Chemistry
32
(Me, Si),NPF,
+ 2(CF,),CO
A series of methyl- and methoxy-fluorodiazadiphosphetidineshas been obtained 23 by substitution reactions using lithium methoxide, methyl-lithium, or methylmagnesium iodide. Analysis of their variable-temperature 1°Fand 31Pn.m.r. spectra supports the concept of concerted pseudorotation at both phosphorus centres. Treatment of the dimer (13) with the di-N-lithiodiamine (14) gave the zwitterion (16), presumably via the spirophosphorane (1 5).24 The dimer (17) with t-butyl-lithium similarly gave the betaine (18). Both (16) and (18) may be formed in order to relieve ring-strain and/or steric interactions in the intermediate phosphoranes.
(14)
[F,PNBu'], + BdLi (17)
-
F~F --NBU'
I
I
BU~N-~FBU~
(18)
The water-soluble trioxaphosphetan (19) is a good source of singlet oxygen.25It is 106 times more stable at - 5 "Cthan (PhO)3P03and 1.4 times more stable than the ozonide (20).
24
R. K. Harris, M. I. M. Wazeer, 0. Schlak, and R. Schmutzler, J.C.S. Dalton, 1974, 1912. 0. Schlak, R. Schmutzler, H.-M. Schiebel, M. I. M. Wazeer, and R. K. Harris, J.C.S. Dalton,
25
A. P. Schaap, K. Kees, and A. L. Thayer, J. Org. Chem., 1975,40, 1185.
23
1974, 2153.
Quinquecovalent Phosphorus Compounds
33
4 Five-membered Rings
Phospho1ens.-Hexafluorobutadiene adds to phosphines and phosphites to give mixtures of the isomeric phospholens (21) and (22), which readily decompose to give difluorophosphoranes.2sOnly the adducts from phosphetans are stable at room temperature. Whereas the cyclic phosphonites (23) and (24) add to 1,3-dienes at
R,P
+
JJ 'F
room temperature, the phenylethynylphosphonites (25;R = H or Me) fail to react under severe condition^.^' This is ascribed to p n d n interactions, leading to low electrophilicity of the phosphorus. Detailed study28of the variable-temperature lH n.m.r. spectrum of the spirophosphorane (26 ; R = 2-isopropylphenyl)suggests that pseudorotation takes place
via a square-pyramidal intermediate in which the accompanying P-aryl rotation occurs. In (26 ; R = 2,4,6-tri-isopropylphenyI),equivalence of the four aromatic methyls is probably achieved via a trigonal-bipyramidal intermediate or transition state having the phenyl group apical. Difluorophosphoranes are obtained from phosphines and phosphites with CF,OF, (CF30)2,or (CF3S)2,the first being the reagent of choice.29In the presence of the parent phosphine, to suppress ionization, the low-temperature 19F n.m.r. spectrum of the phosphorane (27) shows that the most stable conformation has both 26
27
28 29
D. B. Denney, D. Z . Denney, and Y. F. Hsu, Phosphorus, 1974, 4, 217. N. A. Rezumova, N. A. Kurshakova, Z. L. Evtikhov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1834. G. M. Whitesides, M. Eisenhut, and W. M. Bunting, J. Amer. Chetn. SOC.,1974, 96, 5398. N. J. De'ath, D . Z . Denney, D. B. Denney, and C. D. Hall, Phosphorus, 1974, 3, 205.
34
Organophosphorus Chemistry M e - Me
+ CF,OF
F‘
--++
F
Me
(27) fluorines apical. With increasing temperature the coupling of phosphorus to one fluorine is lost much more rapidly than that to the other, suggesting specific ionization of one fluorine in order to relieve strain. The unstable seven-membered phosphorane (29), formed from the phospholen (28) Diethyl and 1,2-dioxan, decomposed to give both diene and THF as
(28)
f
!IcF3 ---+ x P
(
Ph
CF, (30)
peroxide and (28) gave entirely diene and phosphonite, while the same phospholen and the 1,Zdithieten (30) gave only the phospholen sulphide. 1,3,2-Dioxaphospholans.-The formation of phosphoranes from the 1 ,Zdioxetan (3 1) and PIII compounds has been extended31to phosphites and to methyl diphenylphosphinite. The reactions are first order in each reagent and the rates are the same in benzene as in acetonitrile-benzene (5.5 : l), consistent with concerted addition. from the a-keto-ester (32) and both The 2 : 1 adducts (33) have been
RP +
XJMe2
Me2
__f
R,P”,”M:: ‘0
(31) 30
31 32
L. L. Chang, D. Z. Denney, D. B. Denney, and Y. F. Hsu, Phosphorus, 1974,4,265. P. D. Bartlett, A. L. Baumstark, M. E. Landis, and C. L. Lerman, J. Amer. Chem. SOC.,1974, 96, 5267. A. N. Pudovik, I. V. Konovalova, V. P. Kakurina, E. K. Ofitserova, and L. V. Rakova, J. Gen. Chem. (U.S.S.R.), 1974, 44, 253.
Quinquecovalent Phosphorus Compounds
(RO),P
+ PhCOC0,Et
35
p$olEt
(RO),P,
CO,Ph Et
0
(32)
(33)
cyclic and acyclic phosphites. The reaction is 5 times faster with triethyl than with ethyl ethylene phosphite, and this is held33 to confirm the previously proposed mechanism involving, in the slow step, addition of phosphite to the carbonyl carbon. Similar 2 : 1 adducts (34) have been from benzoyl cyanide. They are crystalline, but 31Pn.m.r. spectroscopy shows them to be mixtures of two isomers.
R, R,
Ra
n X, ,Y P
R a c y _.NMe,
+ PhCOCN
x-P-
I
NMe, CN
X,Y = 0 or NMe (34)
R = HorMe
A full account has appeared35of the preparation and P V + PIII tautomerism of a wide range of tetraoxyspirophosphoranes. N-Chlorodi-isopropylamine has been applied38in a convenient synthesis of spirophosphoranes from cyclic PII1compounds and 1,2- or 1,3-glycols according to the equation: 4
R
+ HO(C),OH +
ClNPr:
-
(?’
R
+ Pr;kH,Cl-
Spirophosphoranes have been obtained 37 by oxidation, with bis(dimethylamin0)phenylphosphine or iodine, of the phosphonites (35) derived from 1,ZdioIs or R
2-amino-alcohols. From a study of the dynamic n.m.r. of a range of P-phenoxy- and P-phenylthio-spirophosphoranes it was concluded3*that phenoxy- and phenylthiogroups have comparable apicophilicities. Some of the spirophosphoranes, e.g. (37), 33
A. N. Pudovik, I. V. Konovalova, V. P. Kakurina, and V. A. Fomin, J . Gen. Chem. (U.S.S.R.), 1974, 44, 249.
M. Willson, R. Burgada, and F. Mathis, Compt. rend., 1975, 280, C , 225. 35 A. Munoz, M. Sanchez, M. Koenig, 2nd R. Wolf, Bull. SOC.chim. France, 1074, 2193. 36 S . A. Bone and S . Trippett, Tetrahedron Letters, 1975, 1583. 37 C. Malavaud, Y . Charbonnel, and J. Barrans, Tetrahedron Letters, 1975, 497. as S. A. Bone, S . Trippett, and P. J. Whittle, J.C.S. Perlrin I , 1974, 2125. 34
Organophosphorus Chemistry
36
a>pR ''
/OPh
\'
* a o F r c l
R=OPh
[ (CF,),COH], pyridine
'
CL
(36)
(37) were prepared from dichlorophosphoranes and 1 ,2-diols in the presence of pyridine. Of the phosphonites (36;R = OPh, SPh, or NMe,) only the last reacted with hexafluoroacetone to give the spirophosphorane analogous to (37). The tetraoxyphosphorane (38) exists entirely in the P V Its variabletemperature 19F n.m.r. spectrum supports the high apicophilicity assigned to the hydrogen atom. Me,
Me,
n O O 'P'
+ [(CFJ)$OH],
I
-
NMe, (38) The fluoro(trifluoromethoxy)phosphoranes (39) formed by the addition of CF,OF to 1,3,2-dioxaphospholans39 were stable at - 80 "C but decomposed at - 40 "C to give the expected 28 difluorophosphoranes (40). The most stable conformations of (40) were as shown, with the ring apical-equatorial.
Ap
0,
P
f
CF@F
R R
=
OMeorPh
-80°C,
-
y7 0-P'
R .F1 (39)
,,OCF3
-4OoC,
~
TLF 0-p*
R'I
F (40)
The addition of tetraoxyspirophosphoranes to Schiff bases is reversible on heating.40Some of the adducts, e.g. (41), show two forms, due to the new asymmetric centre and the centre of asymmetry at phosphorus.
39 40
D. B. Denney, D. 2. Denney, and Y. F. Hsu, Phosphorus, 1974,4, 213. C. Laurenco, D. Bernard, and R. Burgada, Compt. rend., 1974, 278, C , 1301.
37
Quinquecovalent Phosphorus Compounds
Among unpublished work in a review41by Burgada of the work of his group on spirophosphoranes is the use of enamines as oxidizing agents in the reaction of tetraoxyspirophosphoranes with alcohols to give pentaoxyspirophosphoranes, e.g. (42).
1,3,2-Dioxaphospholens.-A wide range of cyclic PII1 compounds has been condensed with a-diketones to give the spirophosphoranes (43).42The phosphoranes (44),which are intermediates in the reactions of acyl phosphites with a-diketones, have been detected in some cases by 31Pn.m.r. spectro~copy.~~
A,B = 0, NMe, or S X = NMe, or OMe Z = CH,CH,, CMe,CMe,, CO, or CHPhCHMe
(R’O),POCOR’ + R3COCOR3
-
R’,R2 = Me or Ph
R3 ,OR’
0-P’,
I
OR‘
+ (R10),P(0)OCR3=CR30COR2
The N-acetylphosphoramidite (45) gave the phosphorane (46) with biacetyl but the iminophosphorane (47) when it reacted with b e n ~ y l Pyrolysis .~~ of (46) gave Nethylacetamide. Tetrabromo-o-benzoquinoneand (45) gave a~etonitrile.~~ Both this quinone and tetrachloro-o-benzoquinone reacted with the phosphoramidites (48) to give the phosphoranes (49). Intermolecular exchange of ligands occurs relatively slowly between the trimethyl phosphite-biacetyl adduct (50) and pentaphenoxyphosphorane in benzene at 25 0C.46The oxonium salt (51) is the suggested intermediate. The ratio of Cacylation to exocyclic O-acylation when the adduct (50) is treated with acetyl chloride depends upon the medium.47In the absence of solvent it is 97 : 3 whereas in 41 R. 42 43
Burgada, Bull. SOC.chim. France, 1975,407. D. Bernard and R. Burgada, Tetrahedron, 1975,31, 797. T. K. Gazizov, A. M. Kibardin, A. P. Pashinkin, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1973,43, 2606.
44 45
A. N. Pudovik, E. S. Batyeva, and V. D. Nesterenko, J. Gen. Chem. (U.S.S.R.), 1974,44, 1383. A. N . Pudovik, E. S. Batyeva, V. D. Nesterenko, and E. I. Gol’dfarb,J. Gen. Chem. (U.S.S.R.), 1974, 44, 976.
46
47
F. Ramirez, S. Lee, P. Stern, I. Ugi, and P. D. Gillespie, Phosphorus, 1974, 4, 21. F. Ramirez, J. F. Marecek, S. L. Glaser, and P. Stern, Phosphorus, 1974, 4, 65.
Organophosphorus Chemistry
38
(EtO),PNHCOMe
+
,OE t
(RCO),
= Me+
(45)
0-P'
I \NHCOMe y
OE t (46)
EtO'
HNCoMe
(EtO),P
+ MeCN
\
(4 7)
(RO),PNHAr + (48)
X X = ClorBr
(49)
t (PhO),PO
3 7 ye ,P-9-P' Me0 OMe
I
pp:OPh 'OPh
I OPh
+
MeCONHEt
OCHPhCOPh
Br
0 '
GPh
-t-
PhOMe
Quinquecovalent Phosphorus Compounds
39
dichloromethane solution it is 20 : 80. Acetyl bromide gives little C-acylation under any conditions and almost exclusive U-acylation in acetonitrile. The oxathiazoles (53) and the oxazoles (54) were obtained on treating the phosphite-a-diketone adducts (52) with N-sulphinylsulphonamidesand sulphonyl isothiocyanates, re~pectively.~~ 0
S
(52)
+ R2S0,NCS
-+
R2S0,N*0
LI
+ (MeO),PO
R' R' (54)
1,2-Oxaphospholens.-Two examples of extraordinarily stable phosphoranes containing 1,2-0xaphospholen rings have appeared, the fused ring dioxyphosphorane (55)49and the spirophosphoranes (56)50being prepared according to Scheme 3. Their stability relative to the corresponding acyclic phosphoryl compounds is a striking demonstration of the stabilizing effect of small rings on phosphoranes. (56; R2 = Ph) is unaffected when kept at 340 "C for 4 h. Heating at 250 "C with solid sodium hydroxide gives a disodium salt, which immediately re-forms (56; R2 = Ph) on acidification. The phosphorane (57) was obtained from trimethyl phosphite and benzylidenebenzoylacetone.61The rates of addition of methyl vinyl ketone to the cyclic phosphites (58), (59), and (60) with a given substituent R were in the order (59) > (60)> (58).52Among the phosphonites (58) the order was R = 4-MeC6H4>C,H5 > 4CICsH4. The phosphoranes (61), previously postulated as intermediates in the formation of benzylphosphonates from phenolic Mannich bases and phosphites, have now been isolated.63They rearrange to phosphonates at 190 "C. Further investigation of the 0-alkylation of carboxylic acids with oxaphospholensS4has shown that the reactions proceed with almost complete inversion of configuration at the alkyl carbon. Benzoic acid and the di-Zoctyl ethyl phosphite benzylideneacetylacetone adduct give predominantly 2-octyl benzoate, which 48
49 60 51 52
R. Neidlein and R. Mosebach, Arch. Pharm., 1974, 307,291 (Chem. Abs., 1974, 81, 25 610). D. Hellwinkel and W. Krapp, Angew. Chem. Internat. Edn., 1974, 13, 542. Y.Segall, I. Granoth, A. Kalir, and E. D. Bergmann, J.C.S. Chem. Cornrn., 1975, 399. B. A. Arbuzov, N. A. Polezhaeva, V. S. Vinogradova, G. I. Polozova, and A. A. Musina, Izuest. Akad. Nauk S.S.S.R., Ser. khint., 1974, 2071. M. P. Gruk, N. A. Razumova, V. V. Vasil'ev, and A. A. Petrov, Zhur. obshchei Khim., 1974,44, 2645.
53 Q4
B. E. Ivanov, L. A. Valitova, L. A. Kudryavtseva, T. G. Bykova, K. A. Derstuganova, and E. I. Gol'dfarb, Bull. Acad. Sci. U.S.S.R., 1974, 23, 636. W. G. Voncken and H. M. Buck, Rec. Trav. chim., 1974,93, 210.
Organophosphorus Chemistry
40
R =
0
Reagents: i, KMn04; ii, H+
Scheme 3
(5 8)
(59)
R = OMe, OEt, SEt, or OAc
RIOoH CH,NEt,
(60)
41
Quinquecoualent Phosphorus Compounds
indicates, if the mechanism is as in (62), that the 2-octyloxy-group is more apicophilic than the ethoxy-group. The methyl vinyl ketone adduct (63) is 106-10s times more reactive than the benzylideneacetylacetoneadduct (64), which is in agreement with the expected greater basicity of the ring oxygen in (63).
(64)
(63)
(62)
1,3,2-0xazaphospholidines.-The pure isomers (65)55and (66; R = H or Me)K6 have been isolated by second-order asymmetric induction and their isomerizations in
(66)
(65)
solution followed polarimetrically. The low AS* values for these processes and the lack of incorporation of deuterium in the presence of D 2 0 show that these isomerizations are true pseudorotation phenomena and are not due to equilibria with PII1 species. Optically active phosphines derived from ephedrine have been condensed with biacetyl, benzil, the imino-ketone PhCOC( :NMe)Ph, and benzylideneacetylacetone, and the equilibration of isomers in the resulting optically active spirophosphoranes has been demon~trated.~? Miscellaneous.-A series of spirophosphoranes has been obtained using the azocompound (67).34Trimethyl phosphite and the nitro-olefin (68) condense to give the 1,2,5-0xazaphospholine (69).681,ZDiols add to the triazaphosphole (70) to give the spirophosphoranes (71), which may be in equilibrium with the corresponding PII1
rt\
x o 'P'
NMe,
X = 0 or NMe, 55 56 b7 58
=tPhN=NCOPh
(67)
-
Ph
A. Klaebe, A. Cachapuz Carrelhas, J.-F. Brazier, and R. Wolf, J.C.S. Perkin I f , 1974, 1668, A. Klaebe, A. Cachapuz Carrelhas, J.-F. Brazier, M.-R.Marre, and R. Wolf, Tetrahedron Letters, 1974, 3971. D. Bernard and R. Burgada, Phoghorur, 1974, 3, 187. E. E. Borisova, R. D. Gareev, T. A. Zyablikova, and I. M. Shermergorn, Zhur. obshchei Khim., 1975, 45, 238.
0rganophosphorus Chemistry
42
P
M5N
(MeO),P
+ MeCH=CplO,)Me
-+- Me<,b
P (OMe),
(68)
(69) species (72).69 On heating above their melting points, the 1,3,5-oxazaphospholines (73) give the N-vinylimidoyl chlorides (74).6o
R'
ClF,C
Xpp
clF$
N-\
F,C-C
(OR1),
/"=CCIR'
\
CF,CI
5 Six-co-ordinate Species Spirophosphoranes and pyridine in solution are in equilibrium with 1 : 1 six-coordinate adducts which in some cases, e.g. (77)61 and (78),62 can be isolated. The
F3CQ
I
,OPh
4g:
O-P-OPh Et3hH
C F3 (75 1
pyridine P
CF3 (76)
CF3
(77)
position of equilibrium varies with the concentration of pyridine, the solvent, and the temperature. With tetraoxyspirophosphoranes the equilibria PrI1+PV+PV1 can be The salt (75) was obtained from the spirophosphorane (76), phenol, and triethylamine.61The structures of (75) and (77) are probably as shown since their l9Fn.m.r. spectra at 25 "C show two signals. Spirophosphoranes with suitably placed tertiary nitrogens probably exist as sixco-ordinate species, e.g. (79) and (80) 63 have 31Pchemical shifts characteristic of PVI 69
60 61 62
63
Y. Charbonnel and J. Barrans, Conipt. rend., 1974, 278, C, 355. K. Burger, E. Burgis, and P. Holl, Synthesis, 1974, 816. F. Ramirez, V. A. V. Prasad, and J. F. Marecek, J. Amer. Chem. SOC., 1974, 96, 7269. A. Munoz, M. Koenig, G . Gence, and R. Wolf, Compt. rend., 1974, 278, C, 1353. A. Munoz, G . Gence, M. Koenig, and R. Wolf, Compt. rend., 1975, 280, C, 395.
Quinquecoualent Phosphorus Compounds
43
44
Organophosphorus Chemistry
species. X-Ray analyses of the fluorophosphoranes (81 ; R = F or Ph) show them to be octahedral, although with considerable distortion in the latter case.64On the other hand, the dhnethylphosphorane (82) is trigonal-bipyramidal. A number of six-co-ordinate ions containing three rings have been described, among them (83) and (86), obtained as In solution the phosphorane (84) isomerized to give (SS), which did not form (83) on treatment with dimethylamine. The expected diastereoisomers (88) and (89) were observed by lH n.m.r. spectroscopy when the spirophosphorane (87) was treated with L-( +)-mandelic acid.66The
+ L-(+)-PhCH(OII)CO,H
+
'(88)
Et,GH,
(89)
intermediate (91), formed in the disproportionation of the tetraoxyspirophosphorane (90) in the presence of triethylamine to give the salt (92), has been detected by 31P n.m.r. spectro5copy.
(90)
It
134 65 66
67
K.-P. John, R. Schmutzler, and W. S. Sheldrick, J.C.S. Dalton, 1974, 1841, 2466. D. Bernard and R. Burgada, Compt. rend., 1974, 279, C, 883. A. Munoz, G . Gence, M. Koenig, and R. Wolf, Bull. Sac. chim. France, 1975, 909. A. Munoz, G . Gence, M. Koenig, and R. Wolf, Compt. rend., 1975, 280, C, 485.
J
Halogenophosphines and Related Compounds ~
BY
J. A. MILLER
1 Halogenophosphines The first wave of theoretical studies on halogenophosphines seems to have passed, and this year's literature has been dominated by studies of the reactions of halogenophosphines. While some of this has been of mechanistic interest, by far the larger part of the literature merely reflects the preparative significance of halogenophosphines to other classes of organophosphorus compounds. The classification of this material has caused the usual headaches, and this year the section headings have been based partly on structural relationships and partly on mechanistic grounds. Reactions with Organometallic Reagents.-Divinylmercury has been used to prepare difluoro(viny1)phosphine(l), which forms an adduct with b0rane.l The authors have commented1 on the basicity of (l), and on the fact that a vinyl group would not be expected, in terms of current theory, to encourage such good donor properties. Hg(CH=CH,),
+ F,PBr + F,P(CH=CH,) (1) 27%
The chiral ferrocenyl derivative (2) has been converted into the phosphine (3).2 Acetylenic anions have been used in the preparation of the arylphosphines (4)3and (5).4 A range of chlorophosphineshas been treated6with indolemagnesiumiodide, to produce the 3-phosphinylindoles (6). +Ph2PCl
I
C,H,Fe
1
a a 4
5
_Ij
CHNMe,
CHNMe, Me
C,H,Fe
E. L. Lines and L. F. Centofanti, Inorg. Chem., 1974, 13, 1517. G. Himbert and M. Regitz, Chem. Ber., 1974, 107, 2513. T. Hayashi, K. Yamamoto, and M. Kumada, Tetrahedron Letters, 1974, 4405. B. I. Stepanov, L. I. Chekunina, and A. I. Bokanov, Zhur. obshchei Khim., 1973, 43, 2648. A. I. Rammov, P. A. Gurevich, S. Y. Baigil'dina, T. V. Zykova, and R. A. Salakhutdinov, Zhicr. obshchei Khim., 1974, 44, 2587.
45
0rganophosphor us Chemistry
46
(6) R', R2 = C1, Ph, or OR Reactions with Simple Alkenes and Aromatics.-The Friedel-Crafts reaction of phosphorus trichloride with benzene and its derivatives is normally catalysed by AlCl,, FeCl,, or ZnCl,, and product yields are often poor. In certain cases this problem may be overcome by the use of SnCI,, as illustrated by the excellent yield of dichloro(pmethoxypheny1) phosphine (7) from anisole.
Tetramethylethylene and dichloro(pheny1)phosphine react in the presence of aluminium trichloride to give the phosphine (8). The formation of (8) has been ascribed to the facile homolysis of the phosphiranium salt (9). Ph
\
Cl/PCMe2cHMe2
(9) The reactions between phosphorus trichloride and alkenes continue to be studied, especially those requiring oxygen, Thus a number of fluoro-ethylenes form mixtures of phosphonic and phosphoric dichlorides,6as do the corresponding chloro-ethyle n e ~ Elimination .~ of HCl from the phosphonic dichlorides produces vinylphosphonic derivatives in stereoselectivefashion. Possible mechanisms of these complex radical reactions have been discussed in considerable detail,1° and a summary appears in Scheme 1. 2-Perfluoromethyl-ethylenes and 2-perchloromethyl-ethylenes have also been shownll to give mainly phosphonyl dichlorides when allowed to react with phosJ. A. Miles, M. T. Beeny, and K. W. Ratts, J. Org. Chem., 1975,40, 343 P. Crens, J. Org. Chem., 1975, 40, 1170. 8 C. B. C. Boyce, S. B. Webb, L. Phillips, and I. R. Ager, J.C.S. Perkin 1, 1974, 1644. C. B. C. Boyce and S. B. Webb, J . Chem. Soc. ( C ) , 1971, 1613, 3987. 10 C. B. C. Boyce, S. B. Webb, and L. Phillips, J.C.S. Perkin I, 1974, 1650. l1 M. Demarcq and J. Sleziona, Phosphorus, 1974, 4, 173. 6
Halogenophosphines and Related Compounds
47
Initiation:
Pathways to products:
R'CHCH (R2) C1
I
00
*PCl,
>CH-CH
"4 iiI
R'CHClCH(R2)PC1,
o=Pcl,
R'
I
7' 2R'
0
>CH-CH
R'
/,' R ''
Scheme 1 The phosphorus trichloride-oxygen-alkene reaction. Suggested pathways to the main products [boxed]. phorus trichloride and oxygen. Simple alkyl chlorides, such as ally1 chloride or propyl chloride, yield complex product mixtures, as shown12for propyl chloride (10). Both these papers l1,l2contain mechanistic discussion which is in general agreement with the above scheme. Other aspects of the reactions of phosphorus trichloride with alkenes have been described, including the y-irradiated reaction which yields the olefin (1l).13 Further perchloryl-fluoride-catalysed alkene-phosphorus trichloride systems have been investigated.l* N-vinylmorpholines (12) react l6 with phosphorus trichloride to give la l3 14
l5
Y. Okamoto, T. Okada, and H. Sakurai, Bull. Chem. SOC.Japan, 1975,48,484. E. I. Babkina, Zhur. obshchei Khim., 1974, 44, 953. S. V. Fridland, N. V. Dmitrieva, and I. V. Vigalok, Zhur. obshchei Khim., 1974, 44, 1261. L. A. Lazukina, V. P. Kukhar, and G. V. Pesotskaya, Zhur. obshchei Khim., 1974,44,2355.
Organophosphorus Chemistry
48 0
II
(Eto),PCH,CH,CH,Cl
(32%)
i-
0
II
(EtO),PCHCICH,Me
II
(EtO),P CKMe CH,Cl
+
(14%)
(44%)
0
II
(EtO),POCHMeCH,C1.
(1 0%)
acetylene, presumably via the vinylphosphonous dichloride (1 3). Copolymerization of dichloro(pheny1)phosphine with styrene has been studied.16
ClJTH=CHN
n W0
(13)
The reactions of tetrafluorodiphosphinewith alkenes,", with allylamine,19 and with allyldifluorophosphine (14) l 9 have been described. These reactions may have either heterolytic (allylamine) or radical [as with (14)] pathways. F,PNHCH,CH= CH,
(F,PCH,),CHPF, 16 17 18 19
N. D. Kazakova, L. B. Iriskina, and S. R. Rafikov, Izuest. Akad. Naulc Kazakh. S.S.R., Ser. khim., 1975, 25, 46. J. G. Morse and K. W. Morse, J. Amer. Chem. SOC.,1973, 95, 8469. J. G. Morse and K. W. Morse, Iiiorg. Chem., 1975, 14, 565. E. R. Falardeau, K. W. Morse, and J. G. Morse, Inorg. Chem., 1974, 13, 2333.
49
Halogenophosphines and Related Compounds
Reactions in which Phosphorus is Electrophi1ic.-These are generally fairly standard substitution reactions. For example, aliphatic amines react 2o with 1,2-bis(difluorophosphiny1)ethane (15) until no further H-N bonds remain. In similar vein, aniline reacts with dichloro(pheny1)phosphine to produce 21 the phosphinous amide (16). F2PCH2CH,PFNMe,
~
R = Me /
PhPC4
Me
+ 4PhNH,
64%hPhP(NHPh),
t 2PhNH3C1
(16) An improved route to dialkylaminodi-iodophosphines(17) has been reported.22 It involves halogen exchange, instead of iodide displacement from phosphorus tri-
iodide, described earlier.23Secondary alcohols may be oxidized to ketones by treatment with sodium hydride and chlorodiphenylphosphine(18) in the presence of air.24 The oxidation appears to take place on the corresponding phosphinite ester.
Biphilic Reactions.-Bicyclic 2 6 and caged 26 structures have been formed by the reaction of cycloheptadiene (19) 26 and bicyclo[2,2,1]heptadiene (20) a6 with dihalogenophosphines (see Chapter 4 for conversion into oxides). Detailed n.m.r. studies show that the salts (21), from (19), are one isomer only. The rates of reaction are dependent upon both the halogen and the carbon substituents at phosphorus. An 2o
21 22
E. R. Falardeau, K. W. Morse, and J. G. Morse, Inorg. Chem., 1975, 14, 132. Y. G. Trishin, V. N. Chistokletov, and V. V. Kosovtsev, Zhur. obshchei Khim., 1974,44,2590. Zh. K. Gorbatenko, N. G. Feshchenko, and T. V. Kovaleva, Zhur. obshchei Khim., 1974,44, 2357.
23
A. M. Pinchuk, Zh. K. Gorbatenko, and N. G. Feshchenko, Zhur. obshchei Khim., 1973, 43, 1855.
I. Shamak and Y. Sasson, Synthesis, 1974, 358. 25 0. Awerbouch and Y . Kashman, Tetrahedron, 1975, 31, 33. z6 S. E. Cremer, F. R. Farr, P. W. Kremer, H. Hwang, G. A. Gray, and M. G. Newton, J.C.S. 24
Chem. Comm., 1975, 374.
50
Organophosphorus Chemistry
MePBr, > PhPBr,
> MePC1, B EtPC1, > PhPCL,
c1
(20)
unexpected scrambling of aromatic substituents has been observed 2 7 during the reaction of 1,4-diarylbuta-1,3-dienes(22) with dichloro(pheny1)phosphine. The products are phospholes (23),and the reaction works well for (22;Ar = Ph),28but with (22;Ar = p-tolyl) the main product is (23;Ar = Ph).27 Ph
I
?h
Further reactions of alkyl pyruvates with halogenophosphines have been described. In a very detailed paper,29extensive n.m.r. and i.r. evidence has been presented for the structures of the diastereoisomeric phosphinic chlorides (24)and the phosphine oxides (25),formed from di- and mono-halogenophosphines respectively. These reactions occur at fairly elevated temperatures, depending upon the halogenoand phosphine used [Ph2PCl(80 "C);EtPC12(80-120 "C);PhPC12(140-150 "C)], the order of reactivity is i n t e r ~ r e t e das~ shown ~ in Scheme 2. Similar reactions have been reported 30 for methyl pyruvate with dichlorophosphines (yields 50-80 %), but with chlorodiethylphosphine ethyl pyruvate yields diethylphosphinic chloride (26) and the dehalogenated phosphine oxide (27). No comment is made on these products, although it seems possible that the dehalogenation may result from adventitious water causing the phosphine to react with the expected product (28).There is a close resemblance between the reactions leading to 27 28
J. I. G. Cadogan, R. J. Scott, R. D. Gee, and I. Gosney, J.C.S. Perkin I, 1974, 1694. I. G. M. Campbell, R. C. Cookson, M. B. Hocking, and A. N. Hughes, J. Chem. SOC.( C ) ,1965, 2184.
29
Yu. Yu. Samitov, I. V. Konovalova, V. P. Kakurina, and A. N. Pudovik, Zhur. obshchei Khim.,
80
S . Kh. Nurtdinov, N. M. Ismagilova, A. I. Mamina, T. V. Zykova, and V. S. Tsivunin, Zhur. obshchei Khim., 1973, 43, 2645.
1974,44, 515.
Halogenophosphines and Related Compounds
R'
\
/ R2
0
II PC1 + MeCC0,R3
\J'
R'
I
-0
(24) R' = C1 (25) R ' = alky1,aryl
Scheme 2 (24), (25), and (28) and those observed with aldehyde^,^^ and it remains to be seen how close they are in pathway. 0
EtJC1
II + MeCC0,Et
0
0
II ll EtJC1 + Et,PCHMe I
Attack by phosphorus at the carbonyl carbon has also been suggestedSaas the pathway leading to the heterocycle (29) from the pseudohalogeno-phosphine(30). However, the corresponding diethylphosphine (31) is converted into the anhydride (32) under the same condition^.^^ The related reactions of simple ketones show some interesting structurereactivity relationships. Thus while diethyl ketone forms the expected 1,Zoxaphospholen 31
39
See J. A. Miller in 'Organophosphorus Chemistry', ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1974, Vol. 5, p. 57; 1975, Vol. 6, pp. 49 and 64. I. V. Konovalova, L. A. Burnaeva, and A. N. Pudovik, Zhur. obshchei Khim., 1974,44, 743.
52
Organophosphorus Chemistry 0
0
&PN==C=O
3.
II
MeCC0,Et
(30)
= PhoroPh+
I I Et0,C
+PC0
MeC-P,
I
R
R
0
2-oxides (33) 33 with dichlorophosphines, the corresponding reaction of diphenyl phosphorochloridite (34) yields the vinylphosphonate (35). Even more striking are
BhO),PCl 3. EGCO (34)
(PhO),k(Et)==CHMe
(35)
74%
the substituent effectsat p h o s p h ~ r u swhich , ~ ~ show the following orders of reactivity, as indicated by differential thermal analysis: with acetone, Pcki > PhPCh > EtaPCla EtPClz with cyclohexanone, PhPCla > EtPC122 Pc13 > EtzPCl At face value, these data suggest that these reactions are complex, and that they are not at all well understood. 33
S. Kh. Nurtdinov, N. M. Ismagilova, I. G. Fillipova, D. V. Shikhmuratova, V. A. Korobchenko, R. B. Sultanova, T. V. Zykova, and V. S. Tsivunin, Zhur. obshchei Khim., 1974, 44, 1678.
Halogenophosphines and Related Compounds
53
The reaction of chlorodiphenylphosphine(18) with trifluoroacetic acid has been reinvestigated and shown34to give the oxide (36) (see Chapter 4 for details). Some of
W K
P&PCl + CF3C02H A PhPCHOPPh,
92%
I
(36)
the complexities35 of the reactions of carboxylic acid acylals (37) with dichlorophosphines have been u n r a ~ e l l e dThe . ~ ~ key intermediates are (38) and (39), produced in an exchange reaction, and the main products are all derivable from these,3sas shown in Scheme 3. 0
0
II II RlPCI, + MeCH(OR2)OCR3 * R1P(Cl)OCR3 + MeCH(Cl)ORz (39)
(38)
(37)
1
(I+
RIP OCR3
C1
(39)
k.R3
II
0
Scheme 3
Dichloro(thieny1)phosphine (41) and analogues have been studied further 37-40 in reactions with various conjugated carbonyl compounds, and a selection is outlined below. The reaction between the phosphine (42) and a-methacrylamide has been rationalized as and the reaction between dichloro(ethy1)phosphine and the furan derivative (43) de~cribed."~ D. J. H.Smith and S . Trippett, J.C.S. Perkin I, 1975, 963. M. B. Gazizov, D. B. Sultanova, V. V. Moskva, A. I. Maikova, and A. I. Razumov, Zhur. obshchei Khim., 1971,41,932. 88 M. B. Gazizov, D. B. Sultanova, A. I. Razumov, L. P. Ostanina, T. V. Zykova, and E. I. Savee'eva, Zhur. obshchei Khim., 1974,44, 1255. 37 V. K. Khairullin and R. Z. Aliev, Zhur. obshchei Khirn., 1974,44, 1683. 313 V. K. Khairullin, L.I. Nesterenko, V. I. Savushkina, and E. A. Chernyshev, Izuest. Akad. Nauk S.S.S.R.,Ser. khim., 1974, 1846. 39 R. Z. Aliev and V. K. Khairullin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 2785. 40 V. K. Khairullin and R. Z. Aliev, Zhur. obshchei Khim., 1974, 44, 2120. 41 I. A. Aleksandrova, L. I. Ufimtseva, V. K. Khairullin, and G. V. Dmitrieva, Zhur. obshchei Khim., 1974,44,2125. 42 M. A. Vasyanina and V. K. Khairullin, Zhur. obshchei Khim., 1974, 44, 48. 34
85
3
Organophosphorus Chemistry
54
ref. 37
ref. 38
/
(41)
ii, CH,=CHCONR, ;
li,iiii
PCH,CH,CN
I
CH,CH,CN
C1
Et\pJ-cN\II Et
+
+H2
_.t
/
/
c1
0
PCH,CH (Me) C(Cl)=fiH,
c1-
R
R = 2-cyanopropyl
(42)
0
ll
EtP [CH,CH (CN)Me],
(43)
O=P-0 Et
Phosphorus heterocycles (44)43 and (45)44 have been formed as shown, and the /3-bromo-ketone (46) is formed by the reaction45 of phosphorus tribromide with the unsaturated ketone (47). Ligand Exchanges Between Phosphorus Groups.-The question of halogen interchange between different halogenophosphines has been in a formidable piece of work, involving nine different phosphorus nuclei. Thus the thermodynamics 43 44 45 46
Y . G. Gololobov and Y . V. Balitskii, Zhur. obshchei Khim., 1975, 44, 2356. L. Dulog, F. Nierlich, and A. Verhelst, Phosphorus, 1974, 4, 197. E. R. Kennedy and R. S . Macomber, J . Org. Chem., 1974, 39, 1952. K. Moedritzer, Phosphorus, 1974, 4, 97.
55
Halogenophosphines and Related Compounds
R
n
Bu N-N
75"C,
+ PCl,
BuN=NBu
+ 3HC1
Et
0
0
II Bu'CH=CHCBU'
i, PBr, ii,H,o+
ll
BdCHBrCH,CBut
55% (46)
(47)
of chlorine acceptance by PIII, P=O, and P=S centres have been evaluated, and translated into the following order of decreasing ability to bond to chlorine:4s
R > il>
0
II MeP > Me,P
P
S
II >" Me,P - P > P > MeP > Me,P
MeP
where the unfilled valences are taken by halogen (bromine or chlorine). A similar theme has been followed in other studies of exchange between halogenophosphines and phosphorus(II1) or Group IV derivative^.^^^ 4 9 As one has come to expect, the exchange reactions are highly dependent upon structural details, and even upon stoicheiometry, as illustrated by the reactions of the methyl esters (48), (49),and (50). These processes are believed to be controlled kinetically and to proceed via onium intermediates. 0
PhJCl
+
MeP(OMe),
(48)*
0
I1 PbPP(Me)OMe
PhlPC1:
II
PkPPPh, + MeP(0Me)Cl
(48)
PhPC1, MePC1,
+ (48) --+ PhP(0Me)Cl + MeP(0Me)Cl
+ Ph,P(OMe) -+ Ph&l
+ MeP(0Me)Cl
PhzPOMeF Ph,PCl
+ MeP(OMe),
(49)
0
Me,SiOMe
p'm*
(50)(c,H,,)2~
II
PbPPPh,
I(
0 (C,HI,),PMe
47 48
49
(96%)
(94%)
K. M. Abraham and J. R. Van Wazer, Inorg. Chem., 1975,14, 1099. K. M. Abraham and J. R. Van Wazer, J . Organometallic Chem., 1975, 85,41. K. M. Abraham and J. R. Van Wazer, J. Inorg. Nuclear Chem., 1975, 37, 541.
56
Organophosphorus Chemistry
Last year,Kobase-catalysed exchanges of PII1halides and P(0)H compounds were described in which new P-0-P or P-P(0) compounds were formed. Further work in this areaK1shows that, in the absence of base (i.e. in conditions where hydrogen chloride could accumulate), no ‘dimeric’ species are present at equilibrium. However, there is again a significant dependence on the nature of the halogenophosphine 0
0
II II R2PH + CP(OBu), + R,PC1 + (BuO),PH (5 1)
ligands, e.g. for dibutyl phosphorochloridite (51) the equilibrium favours the chlorodialkylphosphine for R = alkyl; compare ref. 46. Miscellaneous.-The basicities of a series of fluorophosphines (52) towards borane F RPF,
+
BH,
I
R-P-BH, 1 I
F
have been measured,K2 and shown to diminish in the following manner. No satisfactory correlation was found with JPB or with YBH for the complexes. R = But > Et > C = C M e s Me > NMez > OPri > OMe > SMe > F > C1> Br
Aluminium trichloride complexes with phosphorus trifluoride (53) below AICl,
+
PF,
’-200c+
ALF, + PCI,
(53)
F,P-
AlCI,
-20 0C.K3 Above this temperature, ligand exchange occurs. No evidence for complex formation between aluminium trichloride and phosphorus trichloride or between phosphorus trichloride and boron trifluoride was obtained.K3 Bromomethyl ethyl ether (54) quaternizes halogenophosphines,and kinetics show the reactivity to be that expected for a nucleophilic displacement by p h o ~ p h o r u s . ~ ~ Ha1 BrCH,OEt
+
R2PHal -+
I
R,FH,OEt Br-
(54) 50
Yu. A. Viets, A. A. Borisenko, V. L. FOSS,and I. F. Lutsenko, Zhur. obshchei Khim., 1973,43, 440.
51
V. L. Foss, V. V. Kudinova, Yu. A. Viets, and I. F. Lutsenko, Zhur. obshchei Khim., 1974,44,
52
E. L. Lines and L. F. Centofanti, Inorg. Chem., 1974, 13, 2796. E. R. Alton, R. G. Montemayor, and R. W. Parry, Znorg. Chem., 1974, 13, 2267. L. V. Krut’skaya, L. N. Krutskii, and V. S. Tsivunin, Zhur. obshchei Khim., 1974, 44, 2106.
1209. 53
54
Halogenophosphines and Related Compounds
57
The preparation of chlorodimethylphosphine(55) has been described in 'Inorganic Syntheses', using the route via the disulphide (56).66
The most interesting physical paper of the year has been the gas-phase electrondiffraction study of the structure of the diphosphines (57) and (58).KsIn (58) the phosphorus nuclei are pyramidal, but the P-P bond lengths (longer) and the bond angles at phosphorus ( LXPX larger) are not those predicted by VSEPR theory (in comparison, e.g., to Me2PPMe2). Other physical aspects include an n.m.r. studyK7of the conformation of the phosphines (59), leading to an A-value of 2.0 for the PCl, group. Electron-impact studies of phosphorus trifluoride and tetrafluorodiphosphine (57) have appeared,'j8 WPR2 (57) R = F (58) R = CF,
M4PCN
(59) R = Cl,H,orMe
(60)
and the P-P bond-dissociation energy has been estimated at 57 k 10 kcal mo1-l. The mass spectrum of phosphorus trifluoride has been analysed,6Dand force-field calculations on phosphorus trichloride have been published.6o Structural details have been determined for cyanodimethylphosphine (60) from microwave and vibrational spectra. Silyl and Related Phosphines.-Bis(trifluoromethy1)silylphosphines (61) have been prepared as shown.6 2 Silylated diphosphines have been prepared from halogenophosphines, although yields are variable, as shown for (62) and (63).s3 (CF3,PI
+ ISiR, --%(CF$,PSiR, + H k J (61) R = H or Me
R R Me,SiCl + RPCL,
I I
Me,SiP-PSiMe,
(62) R = C1 17% (63) R = Ph 65% 55
56 57 68
60 61 62
63
G. W. Parshall, Inorg. Synth., 1974, 15, 191. H. L. Hodges, L. S. Su, and L. S. Bartell, Inorg. Chem., 1975, 14, 599. M. D. Gordon and L. D. Quin, J.C.S. Chem. Comm., 1975, 35. C. R. S. Dean, A. Finch, P. J. Gardner, and D. W. Payling, J.C.S. Furaday 1, 1974,70, 1921. D. F. Torgerson and J. B. Westmore, Canad. J. Chem., 1975, 53, 933. G. Cazzoli, J. Mol. Spectroscopy, 1974, 53, 37. J. R. Durig, A. W. Cox, and Y . S. Li, Inorg. Chem., 1974, 13, 2302. L. Maya and A. B. Burg, Inorg. Chem., 1975, 14, 698. H. Schumann and R. Fischer, J. Organomefallic Chem., 1975, 88, 13C.
0rganophosphorus Chemistry
58
High-temperature generation of silicon difluoride has been used 64 to prepare the phosphines (64) and (65), for which n.m.r. and mass-spectral data have been presented. Other n.m.r. studies of silylphosphines have been r e p ~ r t e d . ~ ~ SiF, + PH,
-
F,SiPH, + F,Si(H)PH2 (64)
(65 1
Metallation of silylphosphines by lithium diethylphosphide has been reported for (66; n = 1, 2, or 3), and the resultant anions have been alkylated on phosphorus with methyl chloride. 66 Tris(trimethylsily1)phosphine (67) reacts with Group IV chlorides to produce a wide range of ligand-exchanged products. e 7 Ible,-,SiH,PH,
i, EGPLi; ii, MeCl
Me,-,SiH,PHMe
(Me,Si),P
(66)
(67)
Redistribution reactions of a range of germylphosphines (68) and (69) have been reported.68The phosphines (70; n = 3) and (70; n = 2) react with oxygen to form the germoxanes (71) and (72), re~pectively.~
0
II
2 Halogenophosphoranes ab initio calculations 70 on fluorophosPhysical and Structural Aspects.-Further phoranes have been directed at the question of sp3d- and sp-hybrid models of bond64
65 66
67 68
B9 'O
G. R. Langford, D. C. Moody, and J. D. Odom, Znorg. Chem., 1975, 14, 134. G . Fritz and H. Schafer, 2.anorg. Chem., 1974,409, 137. G. Fritz, H. Schafer, and W. Holderich, Z . anorg. Chem., 1974, 407, 266. H. Schumann, H. J. Kroth, and I. Roesch, Z . Naturforsch., 1974, 29b, 608. A. R. Dahl, C . A. Heil, and A. D. Norman, Znorg. Chem., 1975, 14, 1095. A. R. Dahl and A. D. Norman, Inorg. Chem., 1975, 14, 1093. J. M. Howell, J. R. Van Wazer, and A. R. Rossi, Inorg. Chem., 1974, 13, 1747.
59
Halogenophosphines and Related Compounds
ing. Using a small s and p basis set, the latest study70 shows that addition of dorbitals produces a more stable phosphorane, in line with previous e.g. for phosphorus pentafluoride (73) E is lowered by 0.08 a.u. per bond. The question of permutational isomerism in phosphorus pentafluoride (73) is the subject of an extensive CND0/2 study72of the transition states of processes compatible with the key experiment 73 of Whitesides and Mitchell. These are the Berry pseudorotation (BPR) and turnstile rotation (TR) pathways, and the new calculations show that the BPR transition state is energetically so favourable in comparison with that for TR (barrier difference 11 kcal mol-l) that the latter can be excluded as a mechanism in the case of (73).
F.
/
.I
OOf-O
l
o
(75)
(74)
/R
F,P(F'h)CH \
F,PX
(76) X = C1, Me,or NMe,
Me (77) R = C0,Et or Me
RJF2
MeSPF,
(78)
(79)
It is becoming increasingly clear that the TBP structure for spirophosphoranes cannot be assumed to be preferred over a square-pyramidal structure. Thus the spirofluorophosphoranebased on catechol has been shown 74 to be a square pyramid (74), rather than a TBP (75) as first suggested.76 An appropriate caution has appeared on the use of n.m.r. evidence, taken alone, to decide between these structural po~sibilities.~~ Other n.m.r. studies of fluorophosphoranes include temperature-dependent studies 7 7 on a range of tetrafluorophosphoranes (76), for which BPR appears to be the preferred pathway. It is also reported77that lineshape analysis does not detect square-pyramidal intermediates. Some very elegant lgF n.m.r. spectra have been published 78 for the phosphorane (77; R = C0,Et) bearing a chiral group, and the spectral complexity, compared with (77; R = Me), has been shown not to be the result of restricted rotation. 71
72
73 74
75
76
77 78
A. Strich and A. Veillard, J. Amer. Chem. Soc., 1973, 95,5574. P. Russegger and J. Brickmann, Chem. Phys. Letters, 1975, 30, 276. G . M. Whitesides and H. L. Mitchell, J. Amer. Chem. SOC.,1969, 91,5384. H.Wunderlich, D. Mootz, R. Schmutzler, and M. Wieber, Z . Naturforsch., 1974, 29b, 32. G.0. Doak and R. Schmutzler, J . Chem. SOC.( A ) , 1971, 1295. R. R. Holmes, J. Amer. Chem. SOC.,1974, 96,4143. M. Eisenhut, H. L. Mitchell, D. D. Traficante, R. J. Kaufman, J. M. Deutch, and G . M. Whitesides, J . Amer. Chem. SOC.,1974, 96,5385. D.U. Robert, D. J. Costa. and J. G. Reiss. J.C.S. Chem. Comnr.. 1975, 29.
Organophosphorus Chemistry
60
N.m.r. spectra of the phosphoranes (78)have been analysed, and their dependence upon temperature and concentration has been ascribed to fluorine-bridged spe~ies.7~ The lSF n.m.r. spectrum of methylthiotetrafluorophosphorane (79) has been described in detaiLsO Structural details have appeared for the complex of pyridine with phosphorus pentafluoride (73), and for the phosphorane derivatives (80).82, 83 The force constants of (73) have been determined.84
I
0-P
Me,SiO
R = HorMe
(Ph)F,
(80)
Preparation of Phosphoranes.-New routes to phosphoranes include those dependent upon trifluoromethyl derivatives (81), which have been shown to transfer two fluorR,P + CF,X (81)
-
R,PFz
X = OF,OOCF,, or SSCF,
ines to a range of tervalent phosphorus Application to phenylphosphetan derivatives produces the phosphorane (82),8swhich has been shown to be a mixture of species (82a) and (82b). Similar methods lead to difluorotrialkoxyphosphoranes (83), which by n.m.r. spectroscopy are believed to possess cis- and trans-structures, with one equatorial fluorine.86
(8 3)
(82b)
(824
Difluorophosphoranes are also formed by decomposition of the adducts of hexafluorobuta-l,3-diene(84) with a range of phosphines and phosphorus esters. R,P + F,C=CFCF=CF,
__f
[ 1:l adduct]
A
R,PF,
(84) 79
8o
82
83 84
85 86
J. Grosse and R. Schmutzler, Phosphorus, 1974, 4, 49. R. B. Johannesen, S. C. Peake, and R. Schmutzler, Z . Naturforsch., 1974, 29b,699. W. S. Sheldrick, J.C.S. Dalton, 1974, 1402. K.-P. John, R. Schmutzler, and W. S. Sheldrick, J.C.S. Dalton, 1974, 1841. K.-P. John, R. Schmutzler, and W. S. Sheldrick, J.C.S. Dalton, 1974, 2466. T. R. Anathakrishnan and G. Aruldhas, J . Mol. Structure, 1975, 26, 1. N. J. De’ath, D. Z. Denney, D. B. Denney, and C. D. Hall, Phosphorus, 1974, 3, 205. D. B. Denney, D. Z. Denney, and Y . F. Hsu, Phosphorus, 1974, 4, 213. D. B. Denney, D. Z. Denney, and Y . F. Hsu, Phosphorus, 1974, 4, 217.
Halogenophosphines and Related Compounds
61
Addition of hexafluoroacetone to silylaminophosphines yields 8 8 the fluorophosphorane (85), which on treatment with phosphorus pentafluoride (73) gives the trifluorophosphorane (86). Heating of the phosphoranes (85) leads to their incorporation into a dimeric diazadiphosphetidine (87). F
(Me,Si),NPF,
+ (CF,),C-O
;P-“
1 I ,/*F
N-P
’
P o
(87)
Donors of hydrogen fluoride have been shown to react with various complexes of carbon tetrachloride with halogenophosphines to produce fluorophosphoranes (88). The N-silylimino-derivatives(89) also react with hydrogen fluoride, to give the phosphoranes (90). RnPCl3-n + CCl, + HF
_ +
RnPF5-n (88)
Decomposition of bis(dimethylamino)tris(trifluoromethyl)phosphorane in vacuo leadsg1 to the phosphoranes (91) and (92), characterized by their n.m.r. spectra. 88
8Q
O1
J. A. Gibson and G.-V. Roschenthaler, J.C.S. Chem. Comm., 1974,694. R. Appel and A. Gilak, Chem. Ber., 1974, 107, 2169. R. Appel and I. Ruppert, Chem. Ber., 1975,108,919. D . D. Poulin and R. G. Cavell, Znorg. Chem., 1974, 13, 3012.
62
Organophosphorus Chemistry
Related work on the phosphoranes (93) and (94) has been described,92and a discussion of spectral evidence for the equatorial placement of trifluoromethyl groups presented. The phosphorane (95) has been prepared. 93
(93)
I2 =
(94)
17
=
2 3
(95)
Reactions of Phosphoranes.-Chlorination of the side-chain of benzenes by phosphoms pentachloride has been shown to involve radical intermediates. 94 Under controlled conditions (no oxygen, no light, and moderate temperatures) side-chain chlorination could be directed to essentially one position, e.g. with ethylbenzene (96) as
ring chlorination
(< 1%)
Structural work on the products of addition of phosphorus pentachloride to 1,3dienes suggests that the predominant addition gives the (E)-alkene (97).95 This contrasts with the cis-addition observed recently for acetylenes and phosphorus p e n t a ~ h l o r i d e .The ~ ~ lithium derivative of phenylacetylene reacts with phosphorus pentachloride to produce the phosphine (98).97
92
93 94 95
96 97
D. D. Poulin and R. G. Cavell, Inorg. Chem., 1974, 13, 2324. L. N. Markowskij and E. A. Stookalo, Phosphorrrs, 1974, 4, 237. G. A. Olah, P. Schilling, R. Renner, and I. Kerekes, J . Org. Chem., 1974, 39, 3472. V. I. Zakharov, A. V. Dogadina, L. N. Mashlyakovskii, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1974, 44, 98. A. V. Dogadina, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 2186. B. V. Timokhin, V. 1. Dmitriev, E. F. Grechkin, and A. V. Kalabina, Zhur. obshchei Khim., 1974,44, 2107.
Halogenophosphines and Related Compounds
63
Further examples have appeared of what have become fairly standard addition reactions of phosphorus pentachloride with carbonyl compounds. Thus addition to acetaldehyde produces the vinylphosphonates (99) 9 8 or depending upon 0
II
ChPCH=CHOE t
(99)
CI,PCH=C(Cl) SEt
(100) whether ethyl alcohol or ethanethiol is added to the reaction. The phosphate (101) is formed from methyl vinyl ketone,loOas shown. Other reactions of phosphorus pentachloride include addition to santonin lol and cleavage of y-pyrones.102 0
0
It PC1, + CH,=CHCMe
II
--+ CJPoC(Me)=CHCH,Cl (101)
Phosphorus pentachloride converts dimethyl methylphosphonate into the corresponding dichloride (102) in good yield,lo3if no solvent lo*is used. Vinyl isocyanate (103) reactslo6with phosphorus pentachloride to give an adduct, from which the phosphonyl dichloride (104) may be prepared.
0
ll
MeP(OMe),
+ PCl,
MePCZ,
i, room temp.
CH2=CHNC0 (103)
+ PC&
fi, A
*
73%
0
II
CL$CH=CHNCO (104)
The first stable tetra-alkylphosphorane (105) has been preparedlos as shown, from tetramethyl-lead. Conversion of (105) into a methoxyphosphorane is neatly achieved V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974, 44, 1833. V.V. Moskva, T. Sh. Sitdikova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974, 44, 1650. looV. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974, 44, 707. Io1 A. Frohlich, K. Ishikawa, and T. B. H. McMurry, J.C.S. Perkin I, 1975, 726. lo2 G. A. Poulton and M. E. Williams, J . Heterocyclic Chem., 1975, 12, 219. lo3 H. Quast, M. Heuschmann, and M. 0. Abd el Rahman, Synthesis, 1974, 490. lo4L. Maier, Helv., Chim. Acta, 1973, 56, 492. 1°5 V. V. Doroshenko, E. A. Stukalo, and A. V. Kirsanov, Zhur. obshchei Khim., 1974, 44, 69. lo6K . I. The and R. G . Cavell, J.C.S. Chem. Comm., 1975, 279. 98
QQ
Organophosphorus Chemistry
64
by treatment with methyl trimethylsilyl ether. Another new type of phosphorane (106) has been prepared lo7by treatment of dichlorophosphoranes with hydrazides, and an extensive study has been made of the chemistry of (106).
The reaction between o-aminophenol and trichlorophosphoranes has now been logto give dimeric diazadiphosphetidines(107). Previous suggestions1l0. ll1 shown lo**
had assigned phosphazene structures to these products. The reaction of arylidenecyanoacetamides (108) with phenyltetrachlorophosphorane has been studied.l12 Fluorination of alcohol functions by phenyltetrafluorophosphorane (109) has been 0 NC-C-
lo7 108
ll1 112
I1
A. Schmidpeter and J. Luber, Chem. Ber., 1975, 108,820. A. Schmidpeter and J. Luber, Phosphorus, 1974, 5, 55. I. Kabachnik, V. A. Gilyarov, N. A. Tikhonina, A. E. Kalinin, V. G. Andrianov, Yu. T. Struchkov, and G. 1. Timofeeva, Phosphorus, 1974, 5, 65. M. I. Kabachnik, N. A. Tikhonina, B. A. Korolev, and V. A. Gilyarov, Doklady Akad. Nauk S.S.S.R., Ser. khim., 1972, 204, 1352. H. B. Stegmann and G. Bauer, Synthesis, 1973, 162. M. El-Deek and M. Mohamed, J . Indian Chem. SOC.,1974, 51, 895.
logM.
l10
II
CNH,
Halogenophosphines and Related Compounds
65
and to a range of cc-hydroxycarbonyl compounds and papplied to hydroxy-ethers.l14Complex formation between dimethyltrifluorophosphorane (1 10) and phosphorus pentafluoride (73) has been described,llSand throws into question Me,PF, + PF,
Me2$F2 PF,
(73)
(110)
the assumption of intramolecularity in fluorine-exchangereactions of phosphoranes in general. Phosphorus pentafluoride (73) has been usedlls as an initiator for polymerization of THF. Synthetic Uses of Phosphine-Halocarbon Reactions.-These have been reviewed, and reactions with alcohols, amines, thiols, and carbonyl compounds described.117 Aldoximes are known118 to be converted into nitriles (111) by triphenylphosphine and carbon tetrachloride, and the same reagent, in the absence of base, has now been shown1l9to produce chloro-imines (112) from ketoximes. R T E N
4
Et,N
(111)
R1 = "
Ph,P-CCI, R, = a r y i hRT(CI>=-NR'
'C=NOH
Ph,P-CCl,,
/
R'
(112) 67-87%
Onestep reactions from #I-hydroxy-amines to aziridines (113),leo and from carbamoyl chloride derivatives to isocyanates (1 14),121have been described. Triphenylphosphine dibromide (115) has been used as an agent for cleaving ether linkages in cross-linked polyethers.122 R'CHCH(R2)NHR3
I OH
' ( % R
Ph3P-CC14b
R2 (113) 52-91%
0 RNHC-ll
I1
Ph,P-CCL+
RN=C=O (1 14)
Ph,PBr2 (1 15)
Y. Kobayashi, I. Kumadaki, A. Ohsawa, M. Honda, and Y. Hanzawa, Chem. and Pharm. Bull. (Japan), 1975, 23, 196. 11* D. J. Costa, N. E. Boutin, and J. G. Reiss, Tetrahedron, 1974, 30, 3793. 115 M. Brownstein and R. Schmutzler, J.C.S. Chem. Comm., 1975, 278. 116 F. Andruzzi, A. Pescia, and G. Ceccarelli, Makromol. Chem., 1975, 176, 977. 117 H. Teichmann, Z. Chem., 1974, 14, 216. 118 R. Appel, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 1971, 104, 2025. 119 R. Appel and K. Warnung, Chem. Ber., 1975, 108, 1437. 120 R. Appel and R. Kleinstuck, Chem. Ber., 1974, 107, 5. 121 R. Appel, K. Warning, K.-D. Ziehn, and A. Gilak, Chem. Ber., 1974, 107, 2671. l Z 2 R. Michels and W. Heitz, Makromol Chem., 1975, 176, 245. 113
Phosphine Oxides, Sulphides, and Selenides BY J. A. MILLER
Not an exciting year’s literature, most of which has been concerned with tidying up known reactions, rather than establishing new trends. The highlights have been largely in synthesis, where new caged structures have been made, and where phosphine oxides have been used as handles in more general synthetic operations. 1 Preparation and Structure The structure of the trimers of arylphosphinidene sulphides, (ArPS),, has been incorrectly assigned several times in the past. Two groups1 have independently suggested the same general solution (l), in which two of the sulphurs are placed in a 3,5-dithia-l,2,4-triphosphanering, while the third occurs as a phosphine sulphide. The German paper1 presents detailed 31Pn.m.r. data in support of (l), and three separate routes to (1) are described, while the British work2 also used 19F n.m.r. results (Ar = p-fluorophenyl) to establish structure (1). Previous suggested structures, i.e. (2) and (3), each possess symmetry not compatible with the new data. 9
Phospholen oxides have been the subject of several papers this year. The oxides (4) have been prepared3 as outlined, and n.m.r. and i.r. studies indicate that they are largely enolic in solution. A similar observation has been made4 for the oxides ( 5 ) , M. Baudler, D. Koch, Th. Vakratsas, E. Tolls, and K. Kipker, Z. anorg. Chem., 1975,413,239 M. R. LeGypt and N. L. Paddock, J.C.S. Chem. Comm., 1975, 20. W. R. Purdum and K. D. Berlin, J . Org. Chem., 1974, 39, 2904. K. Forner and H.-G. Henning, Z. Clzem., 1974, 14, 477.
66
Phosphine Oxides, Sulphides and Selenides
67
0 II II
(PhCH,),PH
+
NaH
RICH= C (R') CO, Et
RIAPAPh
d
\CH,Ph
(4 1
R'P
/OEt
'CH,
+ BrCH,CH,CO,Et
i, Arbusov; ii Na-toluene
R2
0 I 2
0
\R1
(5 )
prepared as indicated. Detailed n.m.r. and i.r. studies have appeared5on the products of reactions of A2-phospholen and A3-phospholen 1-oxide carbanions. Thus the 1-methyl 1-oxide (6) can be carboxylated with carbon dioxide, and the major products are found to be a@-unsaturatedcarboxylic acids.
2-Phenylisophosphindoline 2-oxide (7) has been synthesized from the 1,4dibromide (8) by two slightly different routes, each of which gives moderate yields of Ph?(X) (OEt),
+
CH,Br
NaAlH,(OCH,CH,OMe), [when X = 01 or i, heat [when X = lone pair] ; ii, NaAIH,(OCH,CH,OMe),
* (71
CH, Br
(7). A similar ring closure of ae-dibromides has been used7 to produce l-phosphabicycloalkane 1-oxides (9), where n = 1 or 2, by routes outlined previously.8+ The loss of oxygen-18 from the labelled P-0 group in (9) has been studiedloin aqueous media, and rates have been compared with loss of oxygen-18 from related acyclic and monocyclic oxides. In the case of the bicyclo[2,2,1]heptane 1-oxide (9; n = l), S. G. Borleske and L. D. Quin, Pho.~p;phorus,1975, 5, 173. T. H. Chan and K. T. Nwe, Phosphorus, 1974, 3, 225. 7 R. B. Wetzel and G . L. Kenyon, J . Arner. Chem. SOC.,1974,96, 5189. 8 R. B. Wetzel and G . L. Kenyon, 9.Arner. Chern. SOC., 1972,94, 9230. R. B. Wetzel and G . L. Kenyon, J.C.S. Chem. Comm., 1973, 287. lo R. B. Wetzel and G . L. Kenyon, J . Arner. Chem. Suc., 1974, 96, 5199. ti
Organophosphorus Chemistry 0
(91
the relatively enhanced rate has been ascribed to pathways other than BPR being available. Bicyclo[2,2,l]heptadiene reacts with dichloro(methy1)phosphine to produce adducts from which the endo- and exo-isomers of the oxides (10) have been obtained.ll In the presence of chloride ion, the intermediate adducts interconvert, but this may be inhibited by addition of aluminium chloride. The oxides (10) are reduced by
trichlorosilane with net inversion. Treatment of (10) with methyl-lithium produces trimethylphosphine, whose formation is ascribed l1 to the intermediacy of quinquecovalent species. A range of alkyl- and aryl-dichlorophosphineshas been allowed to react l2 with cyclohepta-l,3-diene to form 8-phosphabicyclo[3,2,l]oct-6-ene8-oxides (11) after work-up. The oxides (11) generally form as an epimeric mixture, although with
k - c h l o r o perbenroic acid
R5=J +
0-
+ 0-
complex R = Et or R = Ph, only one isomer was isolated. These oxides behaviour towards rn-chloroperbenzoicacid, with olefin epoxidation and/or oxygen l1
12 13
S. E. Cremer, F. R. Farr, P. W. Kremer, H. Hwang, G. A. Gray, and M. G. Newton, J.C.S. Chem. Comm., 1975, 374. 0. Awerbouch and Y. Kashman, Tetrahedron, 1975, 31, 33. Y.Kashman and 0. Awerbouch, Tetrahedron, 1975, 31, 45.
Phosphine Oxides, Sulphides, and Selenides
69
insertion into a P-C bond being the most common features. Diels-Alder-type dimerizations of (1l), or of the corresponding sulphides, have also been studied.lP A number of routine methods have been applied to the synthesis of chiral phosphine oxides. For example, (+)-1-phenylethyl chloride has been convertedlS into chiral a-methylbenzyldiphenylphosphine oxide (12), while analogous reactions produce (13) as a mixture of diastereoisomers. Very high stereoselectivity is observedls in the conversion of chiral phosphine selenidesinto the corresponding oxides by 0
II
PhCHClMe
\ i, PhPMe;
Ph
ii, H,O,
>!CHMePh Me (1 3)
DMSO. The reaction is catalysed by iodine, and gives up to 83 % stereoselectivity,as shown for (14).
Chiral phosphine oxides have also been preparedl7,l8 by treatment of chiral phosphonium salts with base (see Chapter 1). Details have appeared19of the formation of l ,2-dihydrophosphorin l-oxides (15) by rearrangement of the adducts of various phospholes with aromatic acid chlorides. Also is evidence that the formation of (15 ) is largely controlled by steric factors, whereas the ring-expansion of (15) to give (16) appears to be determined by electronic factors.
Y.Kashman and 0. Awerbouch, Tetrahedron, 1975,31, 53. R. A. Naylor and B. J. Walker, J.C.S. Chem. Comm., 1975,45. 1s M. Mikolajczyk and J. Luczak, Synthesis, 1975, 114. l7 R. Luckenbach, Chem. Ber., 1975,108,803. l8 R. Luckenbach, 2.Nuturforsch., 1975, 30b, 119. 19 F. Mathey, D. Thavard, and B. Bartet, Canad. J. Chem., 1975,53, 355. 14
15
70
Organophosphorus Chemistry
Various phosphinous acid derivatives have been converted into phosphine oxides by standard methods, as in the preparation 2o of acetonyldiethylphosphine oxide (17). 0
II
:Pa:(*
Et2PC1 + BrCH,CMe
Et,PCH,CMe
Addition of diphenylphosphine oxide to nitriles yields z1 the a-iminophosphine oxides (18), and substituent effects on the rate of addition support the ratedetermining addition to the nitrile. Iodide ion aids the conversion 2 z of p-substituted 0
ll
PhP(0)H + RCN
Ph,PC(R)=NH (18)
benzyl diphenylphosphinites into the benzylphosphine oxides (19). The authors found that the corresponding aliphatic phosphinites do not rearrange, contrary to an earlier report 23 that they do so. 0
Ph,POCH,Ar
I/
---b Ph,PCH,Ar (19)
The reaction between chlorodiphenylphosphine and trifluoroacetic acid has been shown2*to yield the oxide (20) as the major product (92 %). This oxide had previously been isolated after an attempt to oxidize diphenyl(trifluoroacety1)phosphine (21).25
Ph2PC1 + CF,CO,H
-
0
0
I1 II Ph,P-CH-OPph, I
0
ll
pbpcc~;,
A previous studyz6of the trifluoroacetic acid reaction described the same product, but its structure was not correctly assigned. Two general routes to a-alkoxyalkylphosphine oxides (22) have been developed 27 as outlined. The oxides (22) are potentially useful in the extraction of uranium salts. S. Kh. Nurtdinov, R. Sh. Gubaidullina, V. S. Kukushkina, R. B. Sultanova, T. V. Zykova, and V. S . Tsivunin, Zhur. obshchei Khin?., 1974, 44, 1461. z1 A. N. Pudovik, T. M. Sudakova, and G. I. Evstaf’ev, Zliur obshchei Khim., 1974, 44, 2410. 22 I. Shahak and Y. Sasson, Synthesis, 1974, 358. 23 A. E. Arbusov and K . V. Nikoronov, Zhur. obshchei Khim., 1948, IS, 2008. 24 D. J. H. Smith and S. Trippett, J.C.S. Perliin Z, 1975, 963. 2 5 E. Lindner, H.-D. Ebert, and J. Junkes, Clicm. Ber., 1970, 103, 1364. 2 6 P. Sartori and R. Hochleitner, 2. anorg. Cliem., 1974, 404, 164. 27 Z. N. Mironova, E. N. Tsvetkov, A. V. Nikolaev, M. I. Kabachnik, and Yu. A. Dyadin, Zhur. obshchei Khim., 1974, 44, 1217. 20
71
Phosphine Oxides, Sulphides, and Selenides
/I,
0
11
0
0
i, MeOH-HCl; ii MeO-RX
,PCH,OCMe
i, PCI,;
\!CH,OR /
0
4
Complex formation by phosphine oxides with metal ions has stimulated other syntheses, as for (23),28(24),29 and (25).30 Other synthetic work in the field of
0
II P(CH,CH,CN),
0 reduce =-
II
P(CH,CH,CH,NH,),
phosphine oxides includes the preparation of various tertiary phosphine oxides, sulphides, and selenides (26) 31 and a range of para-substituted benzonitriles, such as the diphenylphosphinoyl derivative (27).32The technology of phosphine oxide production has been
(XC,H,),P=Y
(26) Y = O , S , o r S e
(27)
2 Reactions Two reviews have been published on the reactions of phosphine oxides. The general utility of vinylphosphine oxides in heterocyclic synthesis is discussed as part of a long 28
29
30 31 32 33
E. G . Amarskii, A. A. Shvets, and 0. A. Osipov, Zhur. obshchei Khim., 1974, 44, 461. R. K. Valetdinov, E. V. Kuznetsov, and T. V. Yakovenko, Zhur. obshchei Khim., 1974,44,284. R. B. King and P. R. Heckley, Phosphorus, 1974, 3, 209. R. F. De Ketelaere, G . P. van der Kelen, and Z. Eeckhaut, Phosphorus, 1974, 5, 43. B. Klabuhn, Phosphorus, 1974, 4, 195. V. V. Malovik, I. K. Mazepa, M. D. Pivovarov, V. Y. Semenii, N. G. Feshchenko, and A. V. Kirsanov, Khim. Tekhnol. (Kieo), 1974, 13.
72
Organophosphorus Chemistry
review3*of the latter topic. Thechemistryof keto-alkylphosphineoxidesis described36 in the second of these reviews. Perhaps the most unusual reaction in this year's literature is the conversion of the bis(o-toly1)phosphines (28) into spirophosphoranes, under oxidative condition^.^^ The oxidation is presumed to result in the formation of the oxides (29), which are
Me
(28) R = PhorMe
(29) \
then cyclized under the influence of acid. This sequence is suggested to occur by intramolecular acylation of a phosphine oxide oxygen by a carboxylic acid, a reaction made all the more unexpected because it involves conversion of a P=O group into a phosphorane, which is shown to be extremely stable. The saga of migrating diphenylphosphinoyl groups continues, and has widened its significance by entering the world of general organic synthesis. Thus the sequence of operations3' outlined in Scheme 1, for cyclohexyl bromide, may be seen as a way of linking an alkyl halide to the carbonyl carbon of an aldehyde, i.e. equivalent to generation of RE--". The key step involves migration of the diphenylphosphinoyl moiety of the oxide (30), and the phosphine oxide may finally be removed by basecatalysed oxygenation, or by a Wittig reaction. Other papers in this series have been directed towards a study of the stereochemistry of the m i g ~ a t i o n ,and ~ ~ a, ~study ~ of the factors which control the product For example, the diastereomeric oxides (3 1) have been separated, and solvolysis of their tosylates in formic acid has been shown to occur with retention at the migrating phosphorus atom and inversion at the migration terminus, the carbon bearing the tosylate [as shown for (32)].38s39 34 35
36 37
38
E. Zbiral, Synthesis, 1975, 775. H.-G. Henning, 2. Chem., 1974, 14, 209. Y. Segall, I. Granoth, A. Kalir, and E. D. Bergmann, J.C.S. Chem. Comm., 1975, 399. A. H. Davidson and S. Warren, J.C.S. Chem. Comm., 1975, 148. F. H. Allen, 0. Kennard, L. R. Nassimbeni, R. 6.Shepherd, and S. Warren, Nature, 1974,248, 670.
F. Allen, 0.Kennard, L. Nassimbeni, R. Shepherd, and S. Warren, J.C.S. Perkin 11,1974,1530. 4o D. Howells and S. Warren, J.C.S. Perkin 11, 1974, 992. 39
Phosphine Oxides, Sulphides, and Selenides
73
0
II
0
Phpcl
+
PQ
oMgBr CHOTS
I
he
(30)
CHR Reagents: i, BuLi; ii, MeCHO; iii, TsC1-base; iv, CF3COaH; v, BuLi-02; vi, NaH, RCHO
Scheme 1 Ph
t
Me
Ph
0
Me
Addition reactions to qS-unsaturated phosphine oxides continue to be reported, especially those leading to heterocyclic compounds. The acetylenic oxides (33) 11,I a and (34)43undergo the reactions shown. Activation parameters for additions to (33) have been re~0rted.I~ A related route to pyrazoles involves the cycloaddition of a-diazoalkylphosphine oxides (35) to conjugated acetylene~.~~ The initial adducts (36) are readily rearranged as shown. Diels-Alder addition reactions of 1-phenyl-A2-phospholen1-oxide (37) have been to give one isomer of the oxides (38). Fairly standard additions to the vinylphosphine derivatives (39),4s (40),47and (41)48have been described. The products are of potential interest as novel ligands, either directly or after reduction to the corresponding phosphines. 41
42 43 44 45 46
47 48
A. N. Pudovik, N. G. Khusainova, E. A. Berdnikov, and Z. A. Nasybullina, Zhur. obshchei Khim., 1974,44, 222. A. N. Pudovik, N. G. Khusainova, and T. V. Timoshina, Zhiir. obshchei Khim., 1974,44272. G . Himbert and M. Regitz, Chem. Ber., 1974, 107, 2513. A. Hartmann and M. Regitz, Phosphorus, 1974, 5, 21. D. L. Morris and K. D. Berlin, Phosphorus, 1974, 4, 69. R. B. King and J. C. Cloyd, J . Amer. Chem. SOC., 1975, 97, 46. R. B. King and J. C. Cloyd, J . Amer. Chem. SOC., 1975, 97, 53. G. A. Kutyrev, R. A. Cherkasov, and A. N . Pudovik, Zhur. obshchei Khim., 1974, 44, 1017.
74
0rganophosphorus Chemistry R'
R' \
*I1
R2'
PhN? R' = R1 = OEt or Ph
N\
NPh
N ''
R2
0
II
X
It
PlQC-CNR:
+ R2S02N,
I_f
(34)
S
S
ll PbPCH-CH,
+ PhPH,
base __f
ll
Ph$CH,CH,PHPh
(39) (CH,=CH),P=S
+ Me,PH
base :
(Me,PCH,CH,),P=S
(40)
0
I1 Et$CH=CH,
0
I1 + HSP(OEt),
0
-+
0
I1 II Et,PCH,CH,SP(OEt),
N\ ,NS02R2 N
75
Phosphine Oxides, Sulphides, and Selenides
Photochemical studies discussed in last year's Report have been extended. Thus the phosphine oxide (42), produced by photochemical rearrangement of the ccdiazoalkylphosphine oxide (43) and then cycloaddition to mesityl oxide, has been
0
11
MeOH
P T O H +--- [PhPO,]
+
A
I
OMe
to yield olefins on further photolysis. Japanese workers have shown that the dimer (44) of 1-phenylphospholen 1-oxidemay be p h o t ~ l y s e dto~the ~ cage bis-oxide (45) or the phosphindole 1-oxide (46) according to conditions. The oxide (46) was not isolated, but its formation was inferred from the production of the ester (47). Ph
0
Ph
4 0//
(44)
(45)
a7 +
/ \0
Ph
49 50
0
II I OMe
PhPH
(47)
H. Eckes and M. Regitz, Tetrahedron Letters, 1975, 447. H. Tomioka, Y . Hirano, and Y . Izawa, Tetrahedron Letters, 1974, 4477.
76
Organophosphorus Chemistry
Details have appeareds1of the photolysis of the azide (48). Reduction of phosphine oxides to phosphines has been achieved52by use of chlorinated disilanes, produced during the industrial synthesis of polymethylchlorosilanes. The extraction of Ph
I I ByP=O
H0,C-C-OH
(C,H,,),P=O
(5 0)
(49)
(48)
perchloric acid or nitric acid from aqueous phases into organic phases by trioctylphosphine oxide (49)has been reported.53Other aspects of extraction described by Russian groups include that by the oxide (50),64and by a range of methylenebisphosphine 3 Miscellaneous Ionization of phosphinoylacetic acids (51) has been used to determine o* for the R,P(O)CH, group and 01 for the R,P(O) group.s6 Dipole moments have been measureds7for a wide range of compounds of general formula (52), and the results used to assess the degree of multiple-bond formation between M and X. Complexes between boron trifluoride and Group V derivatives (53; X = 0; R = Me or Ph) have been studieds8under equilibrium conditions. For a range of
!!
II R,PCH,CO, H (51)
R,M=X R,M=X (52) M = P or As X = O , S , or Se
(53) R = Me, Et, Pr, or Ph M = N,P,orAs
x
=
o-o*-s
organic ligands R, it was found that complex stability decreases in the series M = N%As>P, and the implications of this order are discussed. These results are also compared with those from complexes of (53) with iodine, metal ions, or protons. Molecular complexes of trioctylphosphine oxide (49) 6 9 with iodine, and of various tertiary phosphine sulphides 6o with iodine, have been reported, and the relation of the latter to the sulphide ionization energy has been described.60Redistribution of ligands in boron trihalide complexes of phosphine derivatives (53; R = Me; X = 0 or S) has been reported.61
03
M. J. P. Harger, J.C.S. Perkin I, 1974, 2604. G. Deleris, J. Dunogues, and R. Calas, Bull. SOC.chim. France, 1974, 672. M. Niitsu and T. Sekine, J. Inorg. Nuclear Chem., 1975, 37, 1054.
54
A. K. Miftakhova, M. G. Zimin, N. I. Bairamova, and V. F. Toropova, Zhur. analit. Khim.,
55
Z. A. Berkman, L. E. Bertha, G. M. Vol’dman, A. N. Zelikman, and M. I. Kabachnik, Zhur. neorg. Khim., 1974, 19, 2839. E. N. Tsvetkov, R. A. Malevannaya, L. I. Petrovskaya, and M. I. Kabachnik, Zhur. obshchei Khim., 1974, 44, 1225. R. R. Carlson and D. W. Meek, Inorg. Chem., 1974, 13, 1741. R. Bravo, M. Durand, J.-P. Laurent, and F. Gallais, Compt. rend., 1974, 278, C, 1489. R. P. Lang, J . Phys. Chem., 1974,78, 1657. F. I. Vilesov, S. N. Lopatin, V. I. Vovna, R. Paetzold, and K. Niendorf, Z . phys. Chem. (Leipzig), 1974, 255, 661. M. J. Bula, J. S. Hartman, and C. V. Raman, Canad. J. Chem., 1975, 53, 326.
51 6,
1974,29, 1771.
58 57
68 59 60
61
Phosphine Oxides, Sulphides, and Selenides
77
Calculations of the SCF MO LCAO type have been reported 62 for the oxides (54) and (55). Comparison of their U.V. spectra with predicted spectra is improved if d-orbitals are included in the basis set used for the latter. Photoelectron spectra for various phosphine oxides have been described.63 X-Ray analyses of the phospholen oxides (56) have been published;64see refs. 3 and 4.
62
V. V. Penkovsky and E. V. Lavrinenkoomecinskaja, Phosphorus, 1974, 3, 247. Fliick and D. Weber, 2. Naturforsch., 1974, 29b,603. D. M. Washechek, D. van der Helm, W. R. Purdum, and K. D. Berlin, J . Org. Ckern., 1974,39, 3305.
~33 E. 64
5 Tervalent Phosphorus Acids BY 6. J. WALKER
1 Introduction For the third year in succession the amount of significant work in this area has decreased. This is disappointing since there are a number of aspects, for example stereoisomerism and phosphorus p,, bonding, which are both potentially interesting and relatively little studied. The reactions of phosphorus(rI1) esters with polyhalogeno-compounds are included in a recent review.l
2 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-Attack on Saturated Carbon. The Arbusov reaction has been widely used in synthesis; examples include the preparation of (phosphonoacy1)carbazoles (1) and various phostones (2).3 The reaction of 2-chloroethyl phosphites with chloromethyl sulphides gives only the phosphonates (3) and no trace of the
alternative diphosphorus c o m p o ~ n dN-l,2,2,2-Tetrachloroethylamides .~ (4) give the expected phosphonate (5) on reaction with triethyl pho~phite.~ Treatment of (5) with triethylamine gives the vinylphosphonate (6) ; however, the phospliine oxide (7) is 2
4
H. Teichmann, Z . Chem., 1974, 14, 216. D. Kh. Yarmukhametova, B. B. Kudryavtsev, and L. I. Anpilova, Zzcest. Aknd. Nauk S.S.S.R., Ser. khim., 1974, 435 (Chem. Abs., 1974, 81, 63 721d). H. Stutz and H. G. Henning, Z . Chem., 1975, 15, 52. 0. E. Nasakin, V. V. Kormachev, 1. A. Abramov, E. L. Gefter, and V. A. Kukhtin, Zzuest. V. U.Z ., Khim. i khim. Tekhnol., 1974, 17, 1039 (Chem. Abs., 1974, 81, 169 603g). B. S. Drach, E. P. Sviridov, and Ya. P. Shaturskii, Zhur. obshchei Khim., 1974,44, 1712 (Chem. A h . , 1975, 82, 4371n).
78
79
Tervalent Phosphorus Acids C1,CCHClNHCOR
f
(EtO),P
/
I_f.
,NHCOR
C13CCH
(4)
\ Ph,POE t
cL$-c
rHCoR
cl&-c
‘PPh,
//
/NHCoR \
0
obtained directly from the reaction of (4) with ethyl diphenylphosphinite,possibly indicating the greater basicity of phosphinites. The mechanism of dealkylation of trialkyl phosphites with hydrogen chloride has been investigated. Some 31P n.m.r. studies of trineopentyl phosphite-hydrogen chloride mixtures show reversible protonation at phosphorus. These results, together with a kinetic study, suggest that the initial protonation is followed by slow nucleophilic displacement of the alkyl group by either hydrogen dichloride anion or a second molecule of hydrogen chloride (see Scheme 1). Further information on the
(RO),P + HCl
OR
+ (RO),P
+/
No + RC1 + HCI
C1- A (RO),P
H ‘
H ‘
Reagents: i, HCI
Scheme 1
mechanism of the Arbusov reaction is also available (see Cyclic Esters of Phosphorous Acid, p. 101). The phosphonate cyclic acetals (8) and (9) have been prepared from the corre0 ( O0p M e 3
13
(Et0)3P*
[0oh!(OEf),
B. S . Drach, E. P. Sviridov, and A. V. Kirsanov, Zhur. obshchei Khim., 1975,45,12 (Chem. Abs., 1975, 82, 156 458j).
H. R. Hudson and J. C. Roberts, J.C.S. Perkin ZI, 1974, 1575.
0rganophosphorus Chemistry
80
sponding quaternary ammonium salts and triethyl phosphite.aWhat is presumably a similar reaction with the phenol (10) gives l-oxa-2-phospha-indanes(11).
(10)
(11)
Aminomethylphosphonates (12) are formed in quantitative yield from the reaction of trimethyl phosphite with substituted aziridines in the presence of nucleophiles.1° The mechanism is presumably as shown.
+
Ph 0
II
PhOMe
+ (MeO),kHPhNPhCHRZCO, R1 (12)
Various vicinal diphosphine derivatives have been prepared l1 via the reaction of diethyl phosphonate anion with 1,Zdichloroethane to give the 1,2-bis(diethyl phosphonate). Surprisingly, (13) is obtained from the reaction of tetrabutoxydiphosphine with methyl iodide.12The mechanism of alkylation and acylation of alkoxydiphosphines has been discussed. 0 (BuO),P-P(OBu),
+
Me1
-
(BuO),P-0-PMe,
I1
Attack on Unsaturated Carbon. Numerous undistinguished reports of additions of secondary and tertiary phosphites to activated alkenes have appeared.13 8 9 10
11 12 19
B. Mlotkowska, B. Costisella, and H. Gross, J.prakt. Chem., 1974,316, 913 (Chem. Abs., 1975, 82, 73 094m). B. E. Ivanov, L. A. Valitova, L.A. Kudryavtseva, T. G. Bykova, K. A. Derstuganova, and E. I. Gol’dfarb, Zzvest. Akad. Nauk S.S.S.R.,Ser. khim., 1974, 672 (Chem. Abs., 1974, 81, 13 5992). M. Vaultier, R. Danion-Bougot, D. Danion, J. Hamelin, and R. Carrie, Compt. rend., 1975, 280, C, 213. C. G. Macarovici and B. Bohm, Studia Univ. Babes-Bolyai, Ser. Chem., 1974,19,9 (Chem. Abs., 1975,82, 73 101m). I. F. Lutsenko, M. V. Proskurnina, and A. L. Chekhun, Phosphorus, 1974, 4, 57. M. I. Kabachnik, T. Y.Medved, I. B. Goryunova, L. I. Tikhonova, and E. I. Matrosov, Izvest. Akad. Nauk S.S.S.R.,Ser. khim., 1974,2290 (Chem. Abs., 1975,82,43 520e); B. P. Lugovkin, Zhur. obshchei Khim., 1974,44, 1038 (Chem. Abs., 1974, 81, 91 647c); G. Borisov, V. Doseva, and A. Terebenina, Zzvest. Otdel. Khim. Nauki, Bulg. Akad. Nauk, 1974, 7 , 25 (Chem. Abs., 1974,81,91 633v); K. Sadoyama and H. Nemura, Japan. Kokai 74 04 212 (Chem. Abs., 1974, 81, 91 7232).
Tervalent Phosphorus Acids
81
X-Ray crystal analysis has shown14that the supposed a-phosphonates (14), from the overworked reaction of dimethyl phosphonate and cyclopenta-2,4-dienones, must be reassigned as /3-phosphonates (15). Since structure (15) has previously been
assigned to another product, presumably we must expect further work in this area. Equally, some recent Russian work,lSdealing with similar reactions in the presence of amine bases, will require revision. The anthracene derivatives (16) are the predictable products from the reaction of anthrones with trialkyl phosphites;lg however, in some cases spiro-anthrones (17) are also formed.
The addition of phosphites to (hexafluoroisopropy1idene)vinylaminesprovides1' isomeric mixtures of enaminophosphonates (19), probably via the ylide (18 ; Ra = OAlkyl). Similar reactions with phosphines give the ylide (18; RZ = Alkyl), which is stable, being unable to undergo an Arbusov-type reaction. Secondary l4 15
16 l7
J. Iball, P. Kaye, and J. A. Miller, J.C.S. Perkin II, 1974, 650. B. A. Arbusov, A. V. Fuzhekova, and A. F. Zinkovskii, Zhur. obshchei Khim., 1975,45, 299 (Chem. Abs., 1975, 82, 140 261d); ibid., p. 257 (Chem. Abs., 1975, 82, 125 4462). M. M. Sidky, M. R. Mahran, and W. M. Abdo, J. prakt. Chem., 1974,316,377 (Chem. Abs., 1974,81, 120 743p). K. Burger and A. Meffert, Annulen, 1975, 316.
82
Organophosphorus Chemistry
phosphite anions react with pyridinium and quinolinium salts to give phosphonates [e.g.(20)], useful as corrosion inhibitors.ls Mixtures of phospholens (21) and (22) are
A vinylic, rather formed in the reaction of phosphinites with hexafluorob~tadiene.~~ than an allylic, halide is replaced in the reaction of mucochloryl chloride with trimethyl phosphite to give the phosphonate (24).20 The nature of the product is presumably due to stabilization of the carbanion in the intermediate (23). Proton transfer to give the imines (25), rather than the alternative Arbusov reaction, is the predominant pathway in the reaction of dialkylphosphorousanilides with activated alkenes.21The cyclic adducts (26) and (28) are formed in the reaction 16 19 20
21
D. Redmore, U.S.P. 3 810 907 (Chem. Abs., 1974, 81, 37 646p). D. B. Denney, D. Z. Denney, and Y. F. Hsu, Phosphorus, 1974,4,217. K. W. Ratts and W. G. Phillips, J. Org. Chem., 1974, 39, 3300. A. N. Pudovik, E. S. Batyeva, and Yu. N. Girfanova, Zhur. obshchei Khim., 1975, 45, 272 (Chem. Abs., 1975, 82, 156 452c). e.g.
Tervalent Phosphorus Acids
cl$ c1
83
+
0
0
CO, R (EtO),PNHAr + ROCOCH=CHCO,R
I
(EtO),P-CH-CH,CO,R
II
NAr
of trialkyl phosphites with 2-nitrobut-2-ene22 and the ketone (27),23respectively. Dialkyl phosphites add to allenephosphonates in the predictable fashion to give alkenebisphosphonates(29).24 The usual rash of reports of phosphite additions to imines has appeared.25Minor 22
23 24
25
E. E. Borisova, R. D. Gareev, T. A. Zyablikova, and I. M. Shermergorn, Zhur. obshchei Khim., 1975,45, 238 (Chem. Abs., 1975, 82, 112 131t). B. A. Arbusov, N. A. Polezhaeva, V. S. Vinogradova, G. I. Polozova, and A. A. Musina, Zzuest. Akad. Nauk S.S.S.R., Ser. khim., 1974, 2071 (Chem. Abs., 1975, 82, 43 517j). S. V. Kruglov, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1974,44,2650 (Chem. Abs., 1975, 82, 112 132u). e.g. I. N. Levashov, N. S. Kozlov, and V. D. Pak, Zhur. obshchei Khim., 1974,44,1112 (Chem. Abs., 1974, 81, 37 606a); I. A. Balykova, V. D. Pak, and N. S. Kozlov, Zhur. obshchei Khim., 1974,44,2432 (Chem. Abs., 1975,82,86 343s); A. N. Pudovik, M. G. Zimin, I. V. Konovalova, V. M. Pozhidaev, and L. I. Vinogradov, Zhur. obshchei Khim., 1975,45,30 (Chem. Abs., 1975, 82, 140 262e).
84
Organophosphorus Chemistry 0
0
II (R'O)2PCH=C=CR2R3
0
II + (RQO),PH
I1
(PO),PCH,-C
HCRZR \
variations include additions to azines,2sto give for example (30), and to iminophosphorus compounds (31).27 In the latter case the initial product (32) rearranges to (33). The addition of tervalent phosphorus compounds to nitrile imines gives the 0
II
H
(RO), PCHPh-N-NECHPh
(30)
RIN=C
p
0
II
P(OR2), 2
+ GPH
--+ RNHC
2
hydrazones (34) or the phosphonium ylides ( 3 3 , depending on the substituents on phosphorus. 13 0 R ~ R +Z R&N-NA~
R' =
Rms:
II
qPCR3=N-NAr
I COR
(34)
Ph,P=CR3N=NAr
I
CH,CO,Et
26
27 28
E. E. Nifant'ev, N. V. Zyk, and M. P. Koroteev, Doklady Akad. Nauk S.S.S.R., 1974,218 1371 (Chem. Abs., 1975,82, 73 099s). H. Gross, B. Costisella, and L. Brennecke, Phosphorus, 1974, 4, 241. I. A. Stepanov, V. N. Chistokletov, and A. A. Petrov, Doklady Akad. Nauk S.S.S.R., 1975, 220, 127 (Chern. Abs., 1975, 82, 156 461e).
Tervalent Phosphorus Acids
85
Reports of additions of phosphites to carbonyl compounds include reactions of 1,3,2-oxazaphospholidines to give perhydro-oxazaphosphorines (36)29 and trimethylsilyl phosphites to give the phosphonate (37) 30 via trimethylsilyl-group Me 'RO)[
+ R2CH0 + OR'
(36) (EtO),POSiMe, + CF,COCF,
B
(EtO), -C(CF&,OSiMe,
(37)
migration. Another example of the deoxygenation of anhydrides with phosphites is provided by the reaction of disubstituted maleic anhydrides to give trans-bifurandiones (38),31although the reaction does depend on the nature of the substituents. 2
o
a
o
+ 2(EtO),P
* o
+ R
2(EtO),PO
R
(38)
The reaction of thiocyclohexanone, prepared in situ from the corresponding 1,ldithiol, with trialkyl phosphites gives the phosphonates (39) and (40).32Allylic phosphites give the rearranged product (41). 0
29
30 31
32
M. A. Pudovik, L. K. Kubardina, and A. N. Pudovik, Zhur. obshchei Khim., 1975, 45, 470 (Chem. Abs., 1975,82, 112 130s). A. N. Pudovik, T. Kh. Gazizov, and A. M. Kibardin, Zhur. obshchei Khim., 1974, 44, 1210 (Chem. Abs., 1974, 81, 78 022a). C. W. Bird and D. Y. Wong, Tetrahedron, 1975, 31, 31. Z . Yoshida, T. Kawase, and S. Yoneda, Tetrahedron Letters, 1975, 235.
4
86
Organophosphorus Chemistry
The reactions of secondary phosphites with phosphacyclohexan-4-0ne~~and indole-3-carboxaldehydes34 give the expected addition products. More interesting is the formation of the seven-membered phosphonate (42) from the reaction of methylenebis(cyc1ohexanone) with hypophosphorous The reactions of secondary
cm HO
P-0
4OH
(42)
phosphites with monosaccharides have been further investigated. Both 2,3-0isopropylidene-D-glyceraldehyde(43) and 2,4-O-ethylidene-~-erythrose (45) react with dimethyl phosphite non-stereospecifically to give (44) and (46), which are 0 CHO
HOCHP(OMe),
0 It
(MeO), PH
kJM%
(45 1
RoNa
*
(46)
racemic at the hydroxy carbon. A similar reaction takes place with the corresponding In the latter case monosaccharide Schiff bases36and with disaccharides [e.g. (47)].37
CHO
HOCHP(OMe),
I. N. Azerbaev, B. M. Butin, and Yu. G. Bosyakov, Izvest. Akad. Nauk Kazakh. S.S.R., Ser. khim., 1974,24, 72 (Chem. Abs., 1975, 82, 112 135x). 34 A. I. Razumov, P. A. Gurevich, and S. Yu. Baigil'dina, Zhur. ubshchei Khim., 1974, 44, 2586 (Chem. Abs., 1975, 82, 57 827x). as V. I. Vysotskii, A. S. Skobun, and M. N. Tilichenko, Zhur. obshchei Khim., 1974, 44, 2109 (Chem. Abs., 1975, 82, 43 522g). 313 H. Paulsen and H. Kuhne, Chem. Ber., 1975,108, 1239. 57 H. Paulsen and H. Kuhne, Chem. Ber., 1974,107,2635.
33
87
Tervalent Phosphorus Acids
the configuration at carbon was determined by n.m.r. studies on the corresponding acyclic penta-acetate and other related cyclic compounds. Indoxalones (48)and their sulphur analogues (49) give benzofurans and benzothiophens on treatment with hypophosphorous acid. The corresponding selenium compounds (50) give hydroxy-4-seleno-1-coumarins from a similar reaction. The
(48) (49) (SO)
X = OotS
X =0
x=s X
= Se
mechanism probably involves reduction followed by dehydration, and some support for this is available from the isolation of the phosphonate (52) from the reaction of the selenochromone (51) with hypophosphorous acid. At higher temperatures (52) gives the selenodihydronaphthalene (53).38
According to Japanese workers, the reaction of diphenylphosphinite anion with benzaldehyde is much more complex than was previously realized.39Depending on the metal cation, as many as six products can be isolated (Scheme 2); some of these, 0
I1 Ph,PM
0
I1
+ PhCHO --+PhCH,OCOPh + PhCH,PPh, + PhCH(OH)PPh, + PhCH,OH + PhCOCOPh + PhCH(0H)COPh Scheme 2
for example benzyldiphenylphosphineoxide, suggest the involvement of free radicals. Similar reactions with p-benzoquinone were less complex, but three products (Scheme 3) were still formed, again depending on the metal cation. A mixture of products was also obtained from the reaction of lithium diphenylphosphinite with 38 39
R. Weber, L. Christiaens, Ph. Thibaut, M. Rensen, A. Croisy, and P. Jacquignon, Tetrahedron, 1974, 30, 3865. T. Emoto, H. Gomi, M. Yoshifuji, R. Okazaki, and N. Inamoto, Bull. Chem. SOC.Japan, 1974, 47, 2449 (Chem. Abs., 1975,82, 57 819w); ibid., p. 2453 (Chem. Abs., 1975, 82, 57 816t).
Organophosphorus Chemistry 0
X
ll
I1
PPPh,
HF2 +
X . Ph,PM +
II
OH
Scheme 3
acetone (Scheme 4).40 The corresponding thiophosphinite and its lithium salt gave the products shown in Scheme 5. 0
II &PLi
+ Me,CO
-
I1 Ph,PCMe,OH
ll
+ Ph,PCMe,CH,COMe + Scheme 4
S
S
II mPR
0
0
+ Me,CO
= Lik
I1 Ph, PCMe,CH,COMe
S
0
ll II + Ph, PCMe,C&COCH,CMe, PPh,
is1
+ QPCMe,CH, ,CO
S
II
F%,PCMe,OH
Scheme 5
Low yields of various acylated phosphorus compounds (55) are formed from the . ~ ~ reactions with tetra-alkoxyreaction of the esters (54) with acid c h l o r i d e ~Similar diphosphines give even worse yields of the acyl phosphites (56).42 The phosphonate 0 R'R2POR3 + FC'COCI (5 4)
(R*O),PP(OR1), + R2COCI
ll
R'R2PCOFC' (55)
(R'O),PCOR2 (56)
(57) is formed in the reaction of diethyl acetyl phosphite with pyruvic acid nitrile, presumably uia an Arbusov-type 40
41 42
M. Yoshifuji, H. Gomi, and N. Inamoto, Bull. Chem. SOC.Japan, 1974,47, 2905 (Chem. Abs., 1975,82, 156 450a). B. N. Laskorin, V. V. Yakshin, and L. I. Sokal'skaya, Zhur. obshchei Khim., 1974, 44, 1716 (Chem. Abs., 1975, 82, 16 899d). M. V. Proskurnina, A. L. Chekhun, and I. F. Lutsenko, Zhur. obshchei Khim., 1974,44, 1239 (Chem. Abs., 1975, 82, 4355k). I. V. Konovalova, E. Kh. Ofitserova, and A. N. Pudovik, Zhur. obshchei Khim., 1975, 45, 235 (Chem. Abs., 1975, 82, 98 072v). 4
43
89
Temalent Phosphorus Acids 0
II
(EtO),POCOMe + MeCOCN
(EtO),K(OCOMe)(CN)Me (5 7)
Attack on Nitrogen. X-Ray diffraction shows that the adduct of hexailuoroacetone azine and 4-ethyl-2,6,7-trioxa-1-phosphabicyclo[2,2,2]octane has the structure (58) rather than the previously proposed (59).**
A new synthesis of mixed carbonates from the reaction of dialkyl azodicarboxylates (60)and tris(dimethy1amino)phosphine in the presence of alcohols has been f-
R ' o ~ c N - ~ ~~1~ ,
R'0,CN=NC02R'
I
H R'02CN-NC02 R'
I
\
(Me,N),P+
JCO, R' (M%N),P + R'O 'C=O
/
t
(Me,N),$
RzO-
OR'
I I N-NH-C-OR2
a-
'c/h 0-
PO
+ [RIO,CN=NH]
The aminophosphine appears to have some catalytic properties, and a mechanism involving initial attack of phosphorus on azodicarboxylateis suggested. However, explanations for the different courses of reactions with triphenylphosphine are unconvincing, and it may well be that pentaco-ordinate phosphorus is involved, since it is known to be stabilized by electronegative groups. 44
A. Gieren, P. Narayanan, K. Burger, and W. Them, Angew. Chem. Internat. Edn., 1974, 13,
45
543. G. Grynkiewicz, J. Jurczak, and A. Zamojski, Tetrahedron, 1975, 31, 1411.
90
Organophosphorus Chemistry
Triphenyl phosphite and triphenylphosphine react with N-chloro-guanidines to give the salts (61), which on treatment with base give the corresponding imides (62).4s R:P + R2NHC=NC1
II
R:i-N=C
/NHRz \
c1-
NH,
HNR2
R:P=N-C
\
Another example of trimethylsilyl-groupmigration is involved in the formation of the phosphoramidate (64) from ethyl diazoacetate and the trimethylsilyl phosphite (63).47 (RO),POSiMe, + N,CHC02Et
+
(RO),P=N-N=CHCO,Et I 1 OSiMe,
(RO),P-N-N=CHCO,E
II I 0 SiMe,
t
(64)
Attack on Oxygen. Phosphines and phosphites have been converted into phosphine oxides and phosphates in excellent yield by reaction with singlet oxygen48or with air in the presence of n-cyclopentadienyl- or n-indenyl-nickel The kinetics of formation of phosphorane (65) in the reaction of phosphites and phosphinites with tetramethyl-1,Zdioxetan have been investigated.60The results
46
47
48 49
50
A. Heesing and G. Imsieke, Chem. Ber., 1974,107, 1536. A. N. Pudovik and R. Gareev, Zhur. obshchei Khim., 1975, 45, 235 (Chem. Abs., 1975, 82, 156 440x). P. R. Bolduc and G. L. Goe, J. Org. Chem., 1974, 39, 3178. N. Hagiwara, N. Takahashi, and H. Kojima, Japan. Kokai 74 24 900 (Chem. Abs., 1975,82, 86 404n). P. D. Bartlett, A. L. Baumstark, M. E. Landis, and C. L. Lerman, J. Amer. Chem. SOC.,1974, 96, 5267.
Tervalent Phosphorus Acids
91
indicate either a concerted or a homolytic mechanism. There is little new in the synthesis of spirophosphoranes by the reaction of phosphorous esters and mines with a-diketones.61(See also Chapter 2.) Two reactions of some interest reported in the Russian literature possibly involve initial attack on oxygen. Phosphorous amides and a-oxophosphonates react to give high yields of the imine (67), presumably by proton transfer in the initial adduct (66).62A similar reaction of the isocyanate (48) with a-oxophosphonates gives a 0
II
(EtO),PNHPh + (EtO),F‘COR
-
(EtO),h-NHPh
I
(EtO),P=NPh
61
62
D. Bernard and R. Burgada, Tetrahedron, 1975,31, 797 A. N. Pudovik, E. S. Batyeva, V. D. Nesterenko, and N. P. Anoshina, Zhur. obshchei Khim., 1974, 44, 1674 (Chem. Abs., 1975, 82,4357n).
92
OrganophosphorusChemistry
mixture of adducts (69) and (70).53 The mechanism shown in the scheme satisfactorily explains the products. The ratio of desulphurization to deoxygenation of oxophosphoranesulphenyl chlorides (71) by tervalent phosphorus depends on the phosphorus substituents, and in both cases involves inversion of configuration at phosphorus in (71).64Trialkyl,
but not triaryl, phosphites react with thiobenzophenone on heating to give a variety of products, including trialkyl thiophosphates and the phosphonates (72).55The 0
0
(RO),P
+
II ,(RO),PS + Ph$HP(OR),+
Ph,C=S
Ph.$=CF'h,
II
+ Ph,CHSP(OR),
(72) authors suggest a mechanism involving initial attack on sulphur, which on the basis of the evidence provided seems as reasonable as the alternatives. The synthesis of (74) is claimed to provide the first example of a phosphonyl isocyanide group.6sThe intermediate isoselenocyanate (73) is deselenated by triethyl phosphite to (74), which rearranges readily to the cyanide (75). Evidence for the 0
0
KNCSe
53 54
55 56
I. V. Konovalova, L. A. Burnaeva, L. S. Yuldasheva, and A. N. Pudovik, Zhur. obshchei Khim., 1974,44,2408 (Chem. A h . , 1975, 82, 98 071q). B. Krawiecka, J. Michalski, J. Mikolajczak, M. Mikolajczyk, J. Omelanczuk, and A. Skowronska, J.C.S. Chem. Comm., 1974, 630. Y . Ogata, M. Yamashita, and M. Mizutani, Tetrahedron, 1974, 30, 3709. W. J. Stec, A. Konopka, and B. Uzninski, J.C.S. Chem. Comm., 1974, 923.
Tervalent Phosphorus Acids
93
structure (74) includes 31P-14N n.m.r. coupling constants. Attempts to prepare the corresponding tervalent isocyanide by a similar route from (76) gave only the cyanide (77a), although the isocyanide seems a likely inte~mediate.~ The isoselenocyanate (76) rearranges to (77b) on gentle heating.
The silyl phosphite (78) reacts with diphenyl disulphide to give (79), which is readily hydrolysed to (80),68 and the reaction sequence has been applied to the
(Me,SiO), P
1
+ (PhS),
0
II 1 OH
HO-P-SPh
-+-
synthesis of phenyl 5’-nucleoside phosphorothioates (81) in virtually quantitative yield. In a related approach, oxidation and sulphurization of nucleotide phosphites 0
I1
PhSP-0
AH
*IR OH
67
60
W. J. Stec, T. Sudol, and B. Uznhski, J.C.S. Chem. Comm., 1975,467. T . Hata and M. Sekine, J. Amer. Chem. SOC.,1974, 96, 7364.
94
Organophosphorus Chemistry
(82) under mild conditions have been achieved by conversion into the silyl phosphite (83) and treatment with 2,2'-dipyridyl disulphide or sulphur followed by hydrolysis, In a further variation on the same theme, the to give (84) and (83, respecti~ely.~~ 0
0
II (R,Si), PO
II HPO --+
"$'-)HA OH
)olR1 ),fr 0
II
(HO),P-0
HO
R,SiO
(82)
(83)
(84)
S
II
(HO),PO
HO (85)
secondary phosphite (86) was treated with bis(trimethylsily1)acetamide and diphenyl disulphide in dry pyridine to give the protected phosphorothioate (87), which was converted into (88) when it reacted with thymidine.60The h a 1 product (88) could be HO
OR
0
0
I O=PH I OH
I O=P-SPh I OH
(86)
0
o=Po Phd
)ff
(87)
OR Th
= Thymine
(88) separated into two diastereomers, but the discussion of the implications of this is rat her naive. Attack on Halogen. The reactions of phosphorous acid derivatives with polyhalogen compounds continue to be investigated.61Stable phosphorus ylides (90) are obtained 59
6o
61
T. Hata and M. Sekine, Tetrahedron Letters, 1974, 3943. M. Sekine and T. Hata, Tetrahedron Letters, 1975, 1711. e.g. F. M. Kharrasova, T. V. Zykova, R. A. Salakhutdinov, V. D. Efimova, and R. D. Shafigullina, Zhur. obshchei Khim., 1974, 44, 2419 (Chem. Abs., 1975, 82, 73 097g).
Tervalent Phosphorus Acids
95
from the reaction of the phosphonite (89) with secondary amines in carbon tetrachloride, presumably via initial attack on halogen.62The reactions of phosphoramidates with various polyhalogen compounds have been investigated and provide (RO),PCH(CO,Et),
+ CCr,
(RO)2P=C(C0,Et),
I
_ +
(RO)2&H(C02Et)2 ECJ
1
+ (RO),P-CH(CO,Et)
C1-
new high-yield routes to aa-dichloro-esters (91), aa-dichlorophenyl-alkanes(92), and trichloromethyl-alkanes (93).63 0
0
II
($W2kl + RCC4Ph
Tervalent phosphorus compounds react with a-cyano-a-halogeno-imides by attack on halogen to give initially an ion-pair (94). The ion-pairs (94; R = Aryl or Alkyl), formed from phosphines, rearrange to (a-ketoketeniminy1)phosphonium salts (99, whereas the ion-pair (94; R = NMe,), formed from aminophosphine, gives the quasiphosphonium salt (96), together with (95; R = NMe,). Presumably, in the latter case, attack of the anion (94) on phosphorus can be via oxygen or nitrogen.'* The salts (95) undergo further cycloaddition to (94) to give (97). If n.m.r. evidencecan be relied on, 1,2-dibromo-1,Zdibenzoylethane and trimethyl phosphite react to give the vinyl phosphate (98); no mechanism is given in the abstract. A new peptide-coupling reagent, benzotriazolyl N-oxotris(dimethy1amino)phosphonium hexafluorophosphate (99), has been prepared from tris(dimethy1amino)phosphine, l-hydroxybenzotriazole, and carbon tetrachloride.6s 0. I. Kolodyazhnyi, L. A. Repina, and Yu. G. Golobov, Zhur. obslzclzei Khim., 1974, 44, 951 (Chem. Abs., 1974, 81, 13 607a). 63 J. H. Harris and W. D. Alley, J. Amer. Chem. SOC.,1974, 96, 5927. 64 M. F. Pommeret-Chasle, A. Foucaud, and M. Hassairi, Tetrahedron, 1974, 30, 4181. e5 G. Haegele, Z . Nuturforsch., 1973, 28b,753 (Chem. Abs., 1974, 81, 13 604x). 66 B. Castro, J. R. Dormoy, G. Evin, and C. Selve, Tetrahedron Letters, 1975, 1219. 62
96
Organophosphorus Chemistry
Me
Me (94)
Me
X(96)
N-PR,
Me (97)
Ph (PhCOCHBr),
+ (MeO),P
-+
PhCOC&-C
0
It
I
-P(OMe),
97
TerualentPhosphorus Acids
Electrophilic Reactions.-Both indolyl and acetylenic gs Grignard reagents react with chloro-phosphites to give the expected products (100) and (101), respectivefy,
MgX
H
and trialkylphosphines can be conveniently prepared by the reaction of triphenyl phosphite with the appropriate magnesium a l k ~ l . ~ ~ Transesterification of trimethyl phosphite with meso-hydrobenzoin gave transmethyl meso-hydrobenzoinphosphite (lO2).'O The structures of (102) and the corresponding phosphate were determined by single-crystal X-ray diffraction studies. The
reaction of phosphorous acid with orthoformates in the presence of water gives dialkyl phosphites, while under anhydrous conditions the phosphonates (103) are also formed.'l 0
(RO),CH
+
0
II (RO),PH 67 68
G9
70
71
It
(HO),PH
(RO),PH
0
II
+ (RO),F+CH(OR),
N . A. Razumova, N . A. Kurshakova, Zh. L. Evtikhov, and A. A. Petrov, Zhur. obshchei Khim., 1974,44, 1866 (Chem. Abs., 1975,82,31 378b). A. I. Razumov, P. A. Gurevich, S. Yu. Baigil'dina, T. V. Zykova, and K. A. Salakhutdinov, Zhur. obshchei Khim., 1974,44,2587 (Chem. Abs., 1975,82,43 5142). W. Wolfsberger and H. Schmidbaur, Synth. React. Inorg. Metal-Org. Chem., 1974, 4, 149 (Chem. Abs., 1974,81, 13 598y). M.G.Newton and B. S . Campbell, J. Amer. Chem. SOC.,1974,96,7790. H. Gross and B. Costisella, J. prakt. Chem., 1974, 316, 550 (Chem. Abs., 1974, 81, 169 601e).
0rganophosphorus Chemistry
943
Spirophosphoranes [e.g. (104)] can be readily synthesized from the corresponding phosphorus(nr) compound and a diol by reaction with N-chlorodi-isopropylamine,a
reagent previously used in the synthesis of alkoxyphosphonium A variety of spirophosphoranes containing P-phenyl and P-methyl bonds have been prepared by the reaction of hydroxy-phosphonites (105) with iodine or with phosphoramidites, both presumably acting as oxidizing agents. 73 Ph PhP(OCH,CH,OH),
--+
(105)
Dimethylphosphine oxide has been prepared by the hydrolysis of a variety of dimethylphosphinous acid derivatives, and its chemistry investigated.74 What appears to be the first general synthesis of optically active tervalent phosphorus esters has been reported.7s The reactions of monochlorophosphines with methanol or propanol in the presence of optically active amines gave phosphinites with an optical purity of at least 10%. The stereochemistry of methyl ethylphenylphosphinite (106) was established as ( + ) - ( R ) by conversion into (+)-(R)- and 0
72 73 74
75
OMe I
OMe I
S. A. Bone and S. Trippett, Tetrahedron Letters, 1975, 1583. C. Malavaud, Y . Charbonnel, and J. Barrans, Tetrahedron Letters, 1975, 497. H. J. Kleiner, Annalen, 1974, 751. M. Mikolajczyk, J. Drabowicz, J. Omelanczuk, and E. Fluck, J.C.S. Chem. Comm., 1975, 382.
99
Terualent Phosphorus Acids
( -)-(S)-ethylmethylphenylphosphine oxides as shown. A similar reaction of (S)ethyl phosphonochloridothioite(107) gave ( )-(S)-0-ethyl 5-ethyl ethylphosphono-
+
thioite (108) with an induced asymmetry greater than 30%.
'i
.. Me,NR 8
(EtS)EtPCI
f
EtOH
Et*/&>SEt
(107)
The reaction of phosphorodichloridateswith nucleosides, followed by oxidation of the phosphites formed [e.g.(log)], provides a potential new method of polynucleotide ROH + ArOPCI, --+
ROPClOAr
R =
(RO),POAr
0
OR' Th
'O":
= Thymine
II
(RO), POAr
synthesis.76 The same group have synthesized phosphoromonoamidate diester nucleotides (110) using phosphiteazide coupling; the last step in the reaction is presumably a Michaelis-Arbusov-type reaction. The sequencecan be repeated to give trinucleotides.7 7 Rearrangements.-Carbohydrate allenic phosphonates [e.g. (1 12)] have been prepared by rearrangement of the acetylenic phosphite (11 l).78 Although dimethylphosphine sulphide co-ordinates with transition metals via sulphur to give (113), gentle heating of the final product gives the tervalent phosphorus form (114) in quantitative yield.79 Oxazaphospholidines rearrange to oxaphospholans (115) in moderate yield on strong heating.s0 76
77 78
79 80
R. L. Letsinger, J. L. Finnan, G. A. Heavner, and W. B. Lunsford, J . Amer. Chem. SOC.,1975, 97, 3278. R. L. Letsinger and G . A. Heavner, Tetrahedron Letters, 1975, 147. H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1732. E. Lindner and H. Dreher, Angew. Chem. Internat. Edn., 1975, 14, 416. 0. N. Nuretdinova, B. A. Arbusov, F. F. Guseva, L. Z . Nikonova, and N. P. Anoshina, Izuest. Akad. Na,uk S.S.S.R.,Ser. khim.,1974, 869 (Chem. Abs., 1974, 81, 49 750f).
100
Organophosphorus Chemistry
koi
R O W Th
+ (EtO),F'Cl
H
OP(OEt),
OH
Th = Thymine
OH
0
I
t
0
I
OEt OH
OH
O
H
ll 1 (BU' 0),P- C
NC
\\
YH
Tervalent Phosphorus Acids S
II
Me, PH
+ XMn(CO),
-
101
Me
(OC)4Mn-S=PH
I
X
I I Me
+
CO
-
Me
I I Me
(OC),Mn-PSH
I
X
Cyclic Esters of Phosphorous Acid.-The cis- and trans-2-methoxy-4-methyl-1,3,2dioxaphosphorinans(1 16) and (118) react stereospecificallywith methyl iodide under certain conditions to give (117) and (119), respectively.8fThe stereochemistriesinvolved were determined in each case from lH and slP n.m.r. spectra, and the results support an sN2 displacement by phosphorus on carbon to give an intermediate which decomposes by an sN2 attack by iodide on the carbon of the methoxy-group, in contrast to previous suggestions.82
..
Me
I
OMe
I
I
0
II
2-Alkyl- or aryl-dioxaphosphorinans show an axial preference for alkyl or aryl substituents in the same way as their chloro- and methoxy-analogues The dioxaphosphorinanswere prepared as non-equilibrium cis-( 12Ittrans-( 122)mixtures by the reaction of the appropriate dichlorophosphine with the diol(l20). The mixtures had equilibrated after standing for a few hours, and the stereochemistries were assigned on the basis of n.m.r. spectra and comparison with the correspondingoxides, where these were of known stereochemistry. The cis-isomer is the thermodynamically more stable when the phosphorus substituent is relatively small, while the transisomer is more stable for t-butyl. The preferred conformations are probably (121a) 81 82
83
R. A. Adamcik, L. L. Chang, and D. B. Denney, J.C.S. Chem. Comm., 1974, 986. B. J. Walker, in 'Organophosphorus Chemistry', ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1974, Vol. 5, p. 85. W. G. Bmtrude, H. W. Tan, and K. C. Yee, J. Amer. Chem. SOC.,1975,97, 573.
Organophosphorus Chemistry
102 R
..
(121a) (121b)
..
11
I
R
(122a) (122b)
and (122a), and the axial preference in the cis case is thought to be due to Psubstituent-lone pair interactions. Unlike 2-substituted-&methyl- 1,3-dioxolans (123), 2-substituted-4-methyl- 1,3dioxaphospholans have a preferred trans stereochemistry (124), as deduced on the
Me - r ) - R (123)
(124)
basis of 31Pand 13Cn.m.r. (see also Chapter 12).842-Phenyl-l,3,2-dioxaphospholan gives the dimer (125) after several weeks at room temperature; traces of water are probably involved since no change took place in samples sealed under dry nitrogen. The dimer (125) was characterized as the corresponding disulphide diastereomeric
2 (J-PhO\
(125)
N.m.r. studies show that solutions of 2,5,5-trimethyl-l,3,2-dioxaphosphorinan (126) slowly establish equilibrium with the dimeric and trimeric forms (127) and (128).86The relative amounts of (127) and (128) formed depend on the concentration of the original solution. 8*
H. W. Tan and W. G . Bentrude, Tetrahedron Letters, 1975, 619. Dutasta, A. C. Guimaraes, J. Martin, and J. €3. Robert, Tetrahedron Letters, 1975, 1519. J. P. Albrand, J. P. Dutasta, and J. B. Robert, J. Amer. Chem. SOC.,1974, 96, 4584.
a5 J. P. 86
Tervalent Phosphorus Acids
103 O-CH&Me,CH,-O
Me2c>P-Me
-+ Me-P
\
/ \0-CH,CMe,CH,-0
(126)
/p-Me
(127)
+
O-CH&Me,C&-O-P-OC&
/ \O-CH2CMe,CH2-O-P
Me
\
MeP
,CM%
-OCH,
Me
(128)
Miscellaneous Reactions.-A new, virtually quantitative, route to arylphosphonates (129) through the photolysis of aryl iodides and dialkyl phosphite anions has been reported. 0
II
(RO),PO- K++ArI hv, ArP(OR),
i- KI
(12%
The previously reported phosphite-pyridine coupling reagent, used in the synthesis of amides and esters, has now been modified for use in the synthesis of peptides and amino-acid esters. A variety of peptides and polypeptides were prepared through the reaction of aryl esters of phosphinous, phosphonous, and phosphonic acids with amino-acids in the presence of pyridine to give (130), followed by reaction
X P'
' Y
I
OCOR
z' (130)
with protected amino-acid. Linear polymers were also obtained from various aminoacids and diamines by a similar procedure.88 The reaction of DL-34ododistearinwith an excess of trimethylsilyl phosphite, followed by monoesterification, gave a high yield of the lecithin analogue (131).89
I
O(CH,),hMe,
87 88
J. F. Bunnett and X. Creary, J. Org. Chem., 1974, 39, 3612. M. Yamazaki, N. Niwano, J. Kawabata, and F. Higashi, Tetrahedron, 1975, 31, 665. A. F. Romnthal, L. A. Vargas, Y.A. Isaacson, and R. Bittman, TetrahedronLetrers, 1975,977.
104
Organophosphorus Chemistry
The competition between nitrogen and phosphorus for co-ordination to borane has been investigated; whereas aminophosphines containing P-N bonds coordinate via phosphorus, aminoalkylphosphines co-ordinate through nitrogen. 3 Phosphonous and Phosphinous Acids and their Derivatives The rearrangement and oxidation of diphenylphosphinites have been investigated. In each case diphenylphosphinic acid and a ketone were ~btained.~'
90 91
C. Jouany, J. P. Laurent, and G. Jugie, J.C.S. Dalton, 1974, 1510. I. Shahak and Y. Sasson, Synthesis, 1974, 358.
6 Q uinquevalent Phosphorus Acids BY R. S. EDMUNDSON
A recently published volume reviews the chemistry and biological properties of organophosphorus pesticides.' 1 Synthetic Methods General.-The year has seen little published work of a novel character within the general area of synthesis. Many reports have dealt with developments based on previously described procedures, and the unfortunate practice of repetitive publication, commented on in previous Reports, continues to occur. Few papers have dealt with methods which were applied to the preparation of derivatives of all classes of acids of quinquevalent phosphorus. The Todd-Atherton reaction has been employed to convert hypophosphorous acid into dialkyl phosphates, and also to prepare phosphonic acid monoesters from available phosphonous acids; hypophosphorous acid and secondary amines in the presence of CC14 yield phosphorodiamidic chlorides.* Phosphoric Acid and its Derivatives.-The hydrogenolysis of mono- and di-aryl phosphates in the presence of PtOz leads to liberation of the (alky1)phosphoric acid Conversion of and arene, with subsequent reduction of the latter to the ~ycloalkane.~ alkyl halides into alkyl dihydrogen phosphates may be achieved by first allowing the halide to react with tetramethylammonium dibenzyl phosphate followed by hydrogenolytic removal of the benzyl groups:4 the trifluoracetolysis of the similarly prepared di-t-butyl esters, e.g. (l), affords a route to phosphoric acids derived from bifunctional halides.s
An improved yield of the 1,3,2-dioxaphospholen (3) is obtained when the pentaoxyphosphorane (2) reacts with acetyl bromide in acetonitrile; under other experimental conditions, e.g. when dichloromethane is used as solvent, or in the absence of 1 2
4 6
M. Eto, 'OrganophosphorusPesticides:Organic and Biological Chemistry', C.R.C. Press Inc., Cleveland, Ohio, 1973. E. E. Nifant'ev, V. S. Blagoveshchenskii,A. S. Sokurenko, and L. S. Sklyarskii, Zhur. obshchei Khim., 1974,44, 108 (Chem. Abs., 1974, 80, 96 089). A. J u g and R. Engel, J. Org. Chem., 1975,40, 244. M. Kluba, A. Zwierzak, and R. Gramze, Roczniki Chem., 1974,48,277 (Chern. Abs., 1974,81, 63 272). M. Kluba and A. Zwierzak, Roczniki Chem., 1974,48, 1603 (Chem. Abs., 1975, 82, 124 647).
105
106
Organophosphorus Chemistry
a solvent, or when acetyl chloride is employed, there is considerableformation of the linear phosphate (4).6
Dialkyl dithiophosphoric acids add to alk-1-ynes at 110 O C 7 and also to vinylphosphine oxides and vinylphosphonic esters.8 (R'O),P(S) SCR2=CH2
RF-CH
(R'O),PS, H
4
The formation of the 2-oxo-2-phenylthio-l,3,2-dioxaphosphorinan (6) from the 2-methoxy-compound ( 5 ) by its reaction with benzenesulphenyl chloride proceeds stereospecifically with no change in the relative configurations of ring methyl group and methoxyl oxygen, and probably proceeds by collapse of a phosphonium salt intermediate. New cyclic trithiophosphates (7) have been prepared.1°
Mk
Mk
(5 1
(6)
(7) R = H or Me
The esters (8) are obtained when thiophosphoric acids, aldehydes, and heterocyclic compounds possessing imide-type NH groups interact in 80 % sulphuric acid.ll (R'O),P(X)SH
-IRTHO
3
+ HN
--+
X = OorS
(R'O),P(X)SCHR'N
3
(8)
F. Ramirez, J. F. Marecek, S. L. Glaser, and P. Stem, Phosphorus, 1974,4, 65. A. N . Pudovik and 0. S. Shulyndina, Zhur. obshchei Khim., 1974, 44, 221. G. A. Kutyrev, R. A. Cherkasov, and A. N. Pudovik, Zhur. obshchei Khim., 1974, 44, 1017 (Chem. Abs., 1974, 81, 78 023). 9 D. B. Denny and M. Moskal, Phosphorus, 1974,4, 77. lo E. E. Nifant'ev, A. I. Zavalishina, S. F. Sovokina, V. S. Blagoveshchenskii, 0. P. Yakovleva, and E. V. Esenina, Zhur. obshchei Khim., 1974,44, 1694 (Chem. Abs,, 1975, 82,43 357). l1 K. Riifenachut, Helv. Chim. A m , 1974, 57, 1658. 6
7
107
Quinquevalent Phosphorus Acids
This procedure thus differs from the conventional Mannich-type reaction with regard to the acidity of the reaction medium, and also from the Tscherniae-Einhorn type of condensation (also carried out in strong sulphuric acid solutions) in respect of the acidity of the imide. A full report has appeared which deals with the preparation of the symmetrical monothiopyrophosphate (9) on a 0.05 molar, or smaller, scale. In certain cases, e.g. when R1 = Me,CH, the compound (9) can be distilled without any conversion into the unsymmetrical thiopyrophosphate (10); neither does isomerization take place in (R'O),P(O)SCl
+ (R'O),PO,H
the presence of HCl, but the conversion of (9) into (10) can be brought about by the presence of amines.12 The mixed anhydride (11) acts as an N-selective benzoylating agent.13
The monophosphorylation of ethylenediamine with dialkyl phosphorochloridates to yield dialkyl N-(2-aminoethyl)phosphoramidates has been claimed to be fea~ib1e.l~ An extensive compilation of data for nitrogen-containingcompounds prepared from p-cumenylphenyl- and o-biphenylylphosphoric acids (as their dichlorides) has been published; this study reveals that the latter system is the more reactive to nucleophilic reagents.I6 Dimethyl sulphoxide converts trichlorophosphorazopolychloroalkanes(12) into N-acylated phosphoramidic dichlorides (1 3).16 RCCLp-PCI, (12) 12
13 14
l5
18
DMSo +
RCONHP(0)CJ
+ MeSCH,CI
(13)
J. Michalski, B. Mlotowska, and A. Skowronska, J.C.S. Perkin I , 1974, 319. P. G. Nair and C. P. Joshua, Chem. and Ind., 1974, 704. L. B. Taran, K. D. Dzhundabaev, and S. A. Sanakoeva, Zzuest. Akad. Nauk. Kirg. S.S.R.,1974, 50 (Chem. Abs., 1974, 81, 25 006). R. J. W. Cremlyn, J. David, and N. Kishore, Austral. J . Chem., 1974, 27, 1065. V. P. Kukhar and A. P. Boiko, Zhur. obshchei Khim., 1974, 44, 2110 (Chem. Abs., 1974, 81, 169 070).
Organophosphorus Chemistry
108
The direct chlorination of amino-acid esters containing tervalent phosphorus (14) leads, as expected, to a higher oxidation level for phosphorus, but also to reaction within the ethoxycarbonyl group, possibly via the phosphonium intermediate indicated.l
Diethyl phosphoroisocyanatidite reacts with 1,Zdiketones (e.g. biacetyl, benzil) to give the 1,3,2-oxazaphospholans(15).18 This, apparently novel, process can be pictured as involving a sequence of rearrangements within an intermediate formed by (EtO),PNCO
*I
RCOCOR
+
(EtO),P -N=C-=O
I
R
+
---+
(EtO),P-N=C=O
I
0-C-R COR
I
COR
COR (15) R = MeorPh
initial nucleophilic attack by tervalent phosphorus on carbonyl carbon; the use of 2-isocyanato-l,3,2-dioxaphospholans and -phosphorinans leads to bicyclic analogues of (15). 1-Ketophosphonates afford phosphorylated 1,3,2-oxazaphospholidines [15; (RO),P(O) in place of COR].lQ The 1,4,2,3-benzoxathiaphosphazine(16) is stable to acid but is rapidly hydrolysed by boiling 2N sodium hydroxide solution.20
Phosphonic and Phosphinic Acids and their Derivatives.-Many papers have appeared which deal with syntheses by conventionalmeans, including the addition of hydrogen phosphonates to carbon-to-carbon, carbon-to-oxygen, and carbon-to-nitrogen multiple bonds, the use of Grignard reagents, of metallic salts of phosphonic acids, of phosphonic dichlorides with diols, as well as by the Arbuzov reaction. Additional Yu. G. Goldobov, L. I. Nesterova, and A. V. Kirsanov, Zhur. obshchei Khim., 1974, 44, 457 (Chem. A h . , 1974, 81, 3309). 18 I. V. Konovalova, L. A. Burnaeva, and A. N. Pudovik, Zhur. obshchei Khim., 1974,44, 261 (Chem. A h . , 1974, 80, 120 844). lQI. V. Konovalova, L. A. Burnaeva, L. S. Yuldasheva, and A. N. Pudovik, Zhur. obshchei Khim., 1974, 44, 2408 (Chem. A h . , 1975, 82, 98 071). 2o W. V. Farrar, Chem. and Ind., 1974, 876. l7
109
Quinquevalent Phosphorus Acids
examples of reactions appearing in last year's Report have been listed, e.g. phosphonic dihalides by the addition of PCI, to alkenes in the presence of perchloryl fluoride21 and the formation of dienylphosphonic dichlorides from dienes and PCl,? Complexities which may arise in apparently simple systems are well illustrated by the formation of chloroalkylphosphonic dichlorides (17) from butanol and 2methylbutan-2-01on treatment with PCl, foIlowed by S02;23reaction may also take place at ester carbonyl groups to give (18) and (19) when carboxylic esters are similarly treated.24 C4P(0)CH2CMeRC1 (17) R = Meor Et
R1CH2C0,R2.
"j& pc';+ so,
C~P(0)CR'=CC1(OR2)
+
C4P(0)CR1ClCOC1
(18)
(19)
A novel route to monohydrogen phosphonic esters (20) starts with esters of methylenediphosphonic acid.2S 0 (EtO),P(O)CH=CHR
ButO-, A
il
+ RCH-CHP-OH
I
OEt (20)
Phosphorothiocyanidates, which tend to isomerize spontaneously to phosphoroisothiocyanidates,are obtained from sulphenyl chloridesand trimethylsilylcyanide.26 Two examples, given below, illustrate the continuing use of silylated intermediatesin preparative work;27the scope of their reactivity in the preparation of phosphinic esters has been summarized.28 Me,P(S)Br + (Me,Si),NH
--+
-
Me,P(S)N(SiMe,),
Me,P(O)OSiMe, + Me,P(S)Br
M'P(S)Br
: [Me,P(S) 1,NH
Me,P(O)OP(S)Me,
The photolytically initiated (350nm radiation) reaction between iodo-arenes and potassium dialkyl phosphates in liquid ammonia compares favourably (yields are 21 22
23 24
25
26 27 28
S. V. Fridland, N. V. Dmitrieva, and I. V. Vigalok, Zhur. obshchei Khim., 1974,44, 1261 (Chem. Abs., 1974, 81, 49 757). V. V. Kormachev, A. V. Merkulov, and E. L. Gefter, Izoest. V. U.Z . Khim. i khim. Tekhnol., 1974, 17, 1349 (Chem. Abs., 1975, 82, 86 331). V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974,44, 2621 (Chem. Abs., 1975,82, 86 335). V. V. Moskva, V. M. Ismailov, S. A. Novzuzov, A. I. Razumov, T. V. Zykova, Sh. T. Akhmedov, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974, 44, 2616 (Chem. Abs., 1975, 82, 86 336). D. Gloyna, H. Koppel, and H.-G. Henning, J . prakt. Chem., 1974,316, 832. A. Lopuzinskii, J. M. Michalski, and W. Stec, Angew. Chem., 1975, 87, 134. H. Steinberger and W. Kuchen, Z . Naturforsch., 1974, 29b, 61 1 ; G. Hiigele, W. Kuchen, and H. Steinberger, ibid., p. 349. W. Kuchen and H. Steinberger, Z . anorg. Chem., 1975, 413, 266.
110
Organophosphorus Chemistry
87-96 %) with other methods for the preparation of arenephosphonic Heating 2-(3-chloropropoxy)-1,3,2-oxazaphospholidines(21) at 140-1 60 "Cbrings about their isomerization to 2-amino-1,Zoxaphospholans (22) and 2-(3-chloropropyl)-2-oxo-l,3,2-oxazaphospholidines(23).30
l-Nitroalkylphosphonatesare now obtainable by the permanganate oxidation of l-aminophosphonates (yields 30-35 %) or from 2-ketophosphonates or 2-alkoxyvinylphosphonates by the action of acetyl nitrate in acetic anhydride (28-86 % yields).31 l-Hydroxy-2-nitroalkylphosphonates are formed by condensation of l-ketophosphonates with aliphatic nitro-compounds, a reaction which proceeds most satisfactorily in the presence of diethyl- and triethyl-amines (yields 15-82 %) although the reaction may be complicated by the formation of carboxamides through a secondary process involving carbon-phosphorus bond breakage.32The alcoholysis or acidolysis of the acetylenic phosphonates (24) in the presence of BF3 and HgO yields 2-ketophosphonates of the type (25), the ( E ) form being obtained irrespective (R'O),P(O)CG CCR2=CHR3
--+
(R'O), P(0) CHzCOCR2= CH R3
(24)
(25) (Et O),P ( 0 ) CR' Rz(0H )
(26)
of the geometry of the starting The l-hydroxyphosphonates(26; R1 = H; R2 = alkyl) give the corresponding l-chloroalkylphosphonateswhen treated with SOCl2,whereas for (26; R1,R2 = alkyl) elimination and formation of unsaturated phosphonates occurs.34 Treatment of diethyl N-(2-R-aminoethyl)phosphoramidates with butyl-lithium yields the 1,3,2-diazaphospholidines (27) ; the expected product from a similar EtO
\pH
NR
0
Me
/ \ MeNH (CH,),Br
J. F. Bunnett and X. Creary, J. Org. Chem., 1974, 39, 3612. 0. N. Nuretdinova, B. A. Arbuzov, F. F. Guseva, L. Z. Nikonova, and N. P. Anoshina, Izuest. Akad. Nauk. S.S.S.R.,Ser. khim., 1974, 869 (Chem. Abs., 1974, 81, 49 750). 31 K. A. Petrov, V. A. Chauzov, N . N. Bogdanov, and I. V. Pastukhova, Zhur. obshchei Khim., 1974,44, 1649 (Chem. Abs., 1974,81, 91 636). 32 A. V. Serdyukova, G . M. Baranov, and V. V. Perekalin, Zhur. obshchei Khim., 1974, 44, 1243 (Chew. A h . , 1974, 81, 105 634). 33 G. Peiffer and P. Courbis, Canad. J. Chem., 1974, 52, 2894. 34 G. Takeshi, H. Yoshida, T. Ogata, H. Inokawa, and S. Inokawa, Nippon Kagaku Kaishi, 1974, 1093 (Chem. Abs., 1974, 81, 91 649).
29
30
Quinquevalent Phosphorus Acids
111
reaction involving diethyl N-(3-aminopropyl)phosphoramidate and sodium hydride, uiz. the azaphospholidine(28), is, however, not formed in this way, but is obtainable as indi~ated.~, Such a marked difference in behaviour of the two phosphoramidates towards a strong base is not easy to explain, but it may be the result of different steric requirements for the cyclization process. The reaction between moist phosphorous acid and triethyl orthoformate seemingly affords only diethyl phosphite, whereas the use of anhydrous phosphorous acid favours the formation of the phosphonate (29); triethyl orthoformate and P,O, give the anhydride (30).38
The action of PCl, on acetaldehyde semimercaptal gives several phosphorus-free compounds but also the phosphonic dichloride (31).37 MeCH(SEt)OH
pc4 * EtSCCl=CHP(O)CL,
+ MeCH(SEtK1 + MeCClJSEt) + CH,=CCl(SEt)
(31)
0-t-Butyl phosphonic esters have been obtained by the deoxygenation of t-butylperoxy alkylphosphonates with triphenylphosphine.s8 Hexafluoroacetone and diethyl trimethylsilyl phosphite react together to give the phosphonate (32), possibly by way of the zwitterionic intermediate
3-Pyridylphosphonic acid esters have been obtained from 3-pyridyl-lithium and their 2-isomers (33; X = 0)are prepared from phosphorochloridates at - 80 0C;40 N-methoxypyridiniummethosulphatesand are convertible into the thiophosphonates
OMe
(33)
(34) R = Cl
(35) R = P(O)(OEt), 35
36 37 3t3 39 40
D. J. Collins, J. W. Hetherington, and J. M. Swan, Austral. J. Chem., 1974, 27, 1759. H. Gross and B. Costisella, J. prakt. Chem., 1974, 316, 550. V. V. Moskva, T. Sh. Sitdikova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974,44, 1650. G. Sosnovsky and M. Konieczny, Phosphorus, 1974,4,255. A. N. Pudovik, T. Kh. Gazizov, and A. M. Kobardin, Zhur. obshchei Khim., 1974, 44, 1210 (Chem. Abs., 1974,81, 78 022). D. J. Collins, J. W. Hetherington, and J. M. Swan, Austral. J. Chem., 1974, 27, 1355.
Organophosphorus Chemistry
112
(33 ;X = S ) by the action of P2S5.41 Another study of the action of triethyl phosphite on penta~hloropyridine~~ makes no mention of the dehalogenation to 2,3,5,6-tetrachloropyridine, as previously reported, but indicates the products to be the 4phosphonate (34) and the 2,4-diphosphonate (35).42 C-Phosphorylation of malonic esters may be achieved by oxidation of the product obtained from the ester, triethylamine, and diethyl phosphor~chloridite.~~ Cyclic phosphonate systems reported during the year include the tetracyclic compound (37) prepared from the phenol (36) by the action of tris(diethy1amino)p h ~ s p h i n ewhile , ~ ~ 2,2'-methylenebis(cyclohexanone) and hypophosphorous acid in acetic acid at 70 "C are said to yield the tricyclic compound (38).46
Peracid oxidation of bicyclic phosphine oxides with carbon-carbon double bonds sufficientlyhindered to prevent, or at least reduce, the extent of epoxidation results in the insertion of oxygen and formation of phosphonate types, e.g. 8-phenyl-8-oxo-8phosphabicyclo[3,2,l]oct-6-ene(39) yields the epoxyphosphonates (41) and (42) in addition to the epoxyphosphine oxide (40).46
phyLBphlL)phr--b 0
0
RC0,H)
41
0
\\
\\
0
\\ ,o
+
\\ ,o
+
p
h
~
V. N. Eliseenkov, N. V. Bureva, and B. E. Ivanov, Khim. geterotsikl. Soedinenii, 1974, 1354 (Chem. Abs., 1975,82, 112 139). S. D. Moshchitskii and L. S. Sologub, Zhur. obshchei Khim., 1974,44,2782 (Chem. Abs., 1975, 82, 86 329).
43 44 45
46
0. I. Kolodyazhnyi, L. A. Repina, and Yu. G. Gololobov, Zhur. obshchei Khim., 1974,44,1275 (Chem. Abs., 1974,81, 105 636). B. E. Ivanov and S. V. Samurina, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1974, 2079 (Chem. Abs., 1975, 82, 86 155). V. I. Vyotskii, A. S. Skoburn, and M. N. Tilichenko, Zhur. obshchei Khim., 1974, 44, 2109 (Chem. Abs., 1975, 82,43 522). Y. Kashtnan and 0. Awerbouch, Tetrahedron, 1975, 31, 45.
p
~
Quinquevalent Phosphorus Acids
113
The product obtained from the thermal dehydration of l-hydroxyethylidenediphosphonic acid has been shown to have the cyclic structure (43) by physical methods.*'
In the synthesis of phenoxaphosphinic acids (44; X = 0) by the reaction of the diphenyl ether with PC13-AIC13, cyclization of the intermediate dichlorophosphine may be extensively reduced by the presence of a methyl group situated meta to the ether linkage;48some new dihydrophenophosphazinicacids (44;X = NH or NMe) have been recorded.49 Resolution of the selenoic acid (45) as its quinine salt has been achieved50and the absolute configuration of 0-2-butyl ethylphosphonothioic acid, chiral at P and C-2, as its 1-phenylethylammoniumsalt (46) has been determined by X-ray A convenient preparation of simple optically active phosphinate esters employs the trifluoroacetolysis of the quaternary salts (47).5a S
EtCHMe-0-P EtP(Se)OH(OEt)
4I
/ To
Et
(45)
(46)
R' R:O* ML,
*
:R
'\p.(
XR'
R' MLi
R2
OMenth.
H,kHMePh
'zR
-
TFAA Mentho-*
'OMenth
"\
/
XR
RZ
(47)
R3 = Me or Et; ML,
= PF,, BF;, or SbCG; X = 0 or S
51
A. J. Collins, G . W. Fraser, P. G. Perkins, and D. R. Russell, J.C.S. Dalton, 1974, 960. J. B. Levy, Israel J. Chem., 1974, 12,779. R. N. Jenkins and L. I. Freedman, J . Org. Chem., 1975, 40, 766. I. A. Nuretdinov, N. A. Buina, E. V. Bayandina, and F. G. Sibatulina, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1974, 483 (Chem. Abs., 1974, 81,49 756). G. H. Y.Lin, D. A. Wustner, J. R. Fukuto, and R. M. Wing, J. Agric. Food. Chem., 1974, 22,
52
K. E. DeBruin and D. E. Perrin, J. Org. Chem., 1975, 40, 1523.
47 48
49 50
1134.
114
Organophosphorus Chemistry
2 Reactions General.-Several studies on hydrazides and related derivatives of quinquevalent phosphorus acids have been recorded;53of separate interest is the formation of the perhydrotetrazaphosphorines (48) and the similar cage compounds (49) from di- and tri-hydrazides, respecti~ely.~~ RS\
R1P(X)(NR2NHRJ),+
,C=O
R4
-
"\,r"-NR3xRs X '
'NR2--NR3
R4
(48)
R' = Ph, PhO, or M e z N Rz = H or Me; R3 = H or Ph; I?, R5 = H, Me, or cyclohexyl; X = OorS
Two studies of the oxidation of thiophosphoryl compounds to the phosphoryl analogues are noteworthy. In the first of these, m-chloroperbenzoic acid oxidizes thiophosphoryl compounds simultaneously, giving either elemental sulphur (sometimes with other types of phosphorus esters) or other cleavage products such as disulphides (and their oxidation products), the exact nature and number of the products depending on the individual starting In the second study, the oxidation of thio- and seleno-phosphoryl compounds was achieved by the use of DMSO in the presence of a strong acid catalyst during 0.17-576 h at 20-80 "C;the compounds R3PX (X = S or Se; R = alkyl, aryl, aryloxy, or alkylamino) yield R3P0 with retention or inversion of configuration at phosphorus, but 2-thiono1,3,2-dioxaphosphorinansreact with complete retention of configuration.66 Triethyl phosphite removes selenium from the ester (50) to give the phosphoroisocyanidate (51), which rapidly rearranges to the phosphorocyanidate (52).67 53
54
5s 56
57
L. A. Cates and T. M. Lemke, J. Pharm. Sci., 1974, 63, 1736; M. V. Kornoukhova, V. I. Lomakina, Yu. A. Mandel'baum, K. A. Gar, N. M. Golyshin, E. M. Bokarov, L. G. Fedoseenko, and M. R. Bodrova, Khim. Sredstru Zashch. Rast., 1972, 194 (Chem. Abs., 1975, 82, 86 333); M. I. Shandruk, N. I. Yanchuk, and A. P. Grekov, Dopovidi Akad. Nauk. Ukrain. R.S.R., Ser. B, 1974,3,349 (Chem. Abs., 1974,81,90 759); A. P. Grekov, M. I. Shandruk, and N. I. Yanchuk, Doklady Akad. Nauk. S.S.S.R., 1974,214,1077 (Chem. Abs., 1974,80,119 852); M. I. Shandruk, N. I. Yanchuk, and A. P. Grekov, Zhur. org. Khim., 1974, 10,2357 (Chem. Abs., 1975, 82, 72 332). J. P. Majoral, R. Kraemer, J. Navech, and F. Mathis, Tetrahedron Letters, 1975, 1481. E. M. Bellet and J. E. Casida, J. Agric. Food Chem., 1974, 22, 207. M. Mikolajczyk and J. Lucsak, Chem. and Ind., 1974, 701. W. J. Stec, A. Konopka, and B. Uznanski, J.C.S. Chem. Comm., 1974,923.
a,,,, +% 115
Quinquevalent Phosphorus Acids Me
Me ) ( -O ) R
indole
c1-
(SO) R = NCSe (51) R = NC
(5 3)
R = CN
(52)
/
H (54)
When activated by N-phosphorylation, pyridine and its benzologues, of which isoquinoline appears to be the most reactive, react with indole and indene in a heterarylation process, e.g. (53) being converted into (54) (R = phenyl or alkoxy).68 The relative amounts of SMe and OMe esters formed on reaction of monothiophosphoric, -phosphonic, and -phosphinic acids with diazomethane (Scheme 1;
R'
\pHs / \
R2
OCHG
-
R'
\pHs
1
/ \
R'
OH
R' i ,
\JO
/\
R2
SH
R1R2= (PhO),; (EtO),; Me,(EtO);Ph,; Ph, Pri; or EG;R3 = H or Ph Reagents: i, R23CNz
Scheme 1
R1 = H) do not appear to depend on the position of the tautomericequilibrium but rather on R2and R3, and on solvent, an increase in dielectric constant leading to more O-methylati~n.~~ It was argued that the ratio of yields of the two isomeric esters depends on the ratio of the rates of reaction of, on the one hand, the anion of the phosphorus acid with the methyldiazonium cation, leading to S-methylation (a soft acid-soft base relationship), and on the other hand, the breakdown of the diazonium cation to the methyl cation and subsequent O-methylation (a hard acid-hard base process). For a series of 00-dimethyl esters (MeO),P(Z)R1 (Z = 0 or S) at 20-100 "C the relative rates of demethylation by R"N (R2= Me or Et), I-, and SCN- appear to be in the order (Z, R); (S, OC6H4N02-4)> (0,OCH=CC12) > (S,SCH,CONHMe) > [0,CH(O,CPr)CCl,] > [0,CH(0H)CCIJ > (0,OMe).60 The loss of phenol from the phosphoramidate (55) upon treatment of this with aqueous triethylamine, and the formation of the hydrogen phosphoramidate (57), is consistent with P-N bond cleavage (a) rather than N-C cleavage (b) in an intermediate (56); the ester (58) does not undergo this reaction under the same conditions. A similar type of intermediate is consistent with the methanolysis of (59) to give (60) although direct proof of this suggestion is lacking. The author makes an interesting 58
59
A. K. Sheinkman, G. V. Samoilenko, and N. A. Klyuev, Zhur. obshchei Khim., 1974,44, 1472 (Chem. Abs., 1974, 81, 91 646). T. A. Mastryukova, M. Orlov, L. S. Butorina, E. I. Matrosov, T. M. Shcherbina, and M. I. Kabachnik, Zhur. obshchei Khim., 1974,44,1001 (Chem. Abs., 1974,81,48 991); T. A. Matryukova, M. Orlov, D. Eremich, and M. I. Kabachnik, ibid., 1974,44,2403 (Chem. Abs., 1975,82, 170 976). €2. Jentzsch and G. W. Fischer, J. prakt. Chem., 1974, 316,249.
0rganophosphorus Chemistry
116
*
(PhO),P(O)NHCONHAr (55)
ll/ PhP
\
(PhO),P(O)NHCH,Ph
(5 8)
0
NHAr MeOH
II/OMe PhP
*
NHCH,CO, R
'NHCH,CONHAr
(59)
(60)
AI = p-tolyl proposal regarding the controlled, but possibly limited, peptide synthesis based upon these results.61 The base-catalysed methanolysis and phenolysis of the acid chlorides R1R2P(0)C1 (R1 = Me, Me,CH, or Me,CCH,; R2 = C1, OMe, or OPh) evidently does not proceed by an elimination-addition sequence since no incorporation of deuterium occurs when the reaction is carried out with MeONa in NaOD, or with PhOHTHF-NaOD. 62 Phosphate and phosphonic esters and phosphoramidates may be monodealkylated by treatment with thiophenoxide or thiolate anions.s3In the dealkylation of quinquevalent phosphorus esters by heating them with purines at 140-210 "C, the alkylating power of the esters decreases in the order phosphate > phosphonate > phosphinate, the extent of alkylation by a given ester depending upon the individual purine base.64 Reactions of Phosphoric Acid and its Derivatives.-2-(NN-Dimethylamino)-4nitrophenyl phosphate is a selective agent for the phosphorylation of unprotected nucleosides.66 The ready availability of many cyclic esters of quinquevalent phosphorus acids and their (very often) ease of ring opening makes them potentially useful compounds for the synthesis of linear esters. Phosphorylated choline and its homologues (61) are obtainable by treatment of cyclic phosphates and related
RP(O)(O'),
2Nd <,,
f:
(c;P
OC&(CH,),CH,hMe,
/
ii
n = 0 or i
RP(*\
0
R = morpholino or substituted benzyloxy Reagents: i, NaCN; ii, MesN, 70-100
0-
(61)
"C
Scheme 2 61 62
63 64
65
M. Mulliez, Tetrahedron Letters, 1974, 2351. C. Hilbert, C. Z. Duschek, G. Zimmerman, and M. Wahren, J . prakt. Chern., 1974,316,790. P. Savignac and G. Lavielle, Bull. SOC.chim. France, 1974, 1506. K. Yamauchi, M. Hayashi, and M. Kinoshita, J. Org. Chem., 1975, 40, 385. Y.Taguchi and Y. Mushika, Tetrahedron Letters, 1975, 1913.
Quinquevalent Phosphorus Acids
117
compounds with trimethylamine at elevated temperatures.66 2-0~0-1,3,2-dioxaphospholans undergo more extensive degradation when acted upon by sodium cyanide 6 7 (Scheme 2). A study has been made of the thermolysis of several halogenoalkyl phosphates in relation to their fire-retardant properties; tris (2,3-dibromopropyl) phosphate, for example, decomposes at 250-260 "C to give 172,3-tribromopropane(67 %), allyl bromide (12%), 1,3-dibromo- (ca. 6 %), and 172-dibromo-propenes(ca. 2 %).68 Thermolysis of bis-(OO-dimethyl phosphorothioyl) disulphide commencing at ca. 140 "C yields methanethiol, dimethyl sulphide, dimethyl disulphide, 00s-trimethyl phosphorothiolate, and 00s-trimethyl phosphorodithioate;6s the corresponding tetrabutyl ester liberates similar sulphur-containingcompounds as well as a mixture of butenes.70Other studies on the thermal stability of metal dithiophosphates 71 and thiophosphoramides72 and related compounds have been made. Peroxyphosphates (62) undergo methanesulphonic-acid-catalysedperhydrolysis to give percarboxylic acids in good yields. 73 Metal dithiocarbamates dealkylate the cyclic thiophosphoric esters (63) under very mild conditions.'* (Et O),P(O)O,CR
98% H,O,-EGO
0-30°C
RCO,H
(62) (6 3)
Aromatic compounds possessing electron-donating groups are selectively monoallylated by allyl diphenyl phosphate; those substrates with electron-withdrawing groups, or which are sterically hindered, are unreactive.76 It has long been generally assumed that the formation of pyrophosphates from phosphate esters and phosphoryl chlorides proceeds by attack by phosphoryl oxygen on the chlorine-carrying phosphorus atom. About 1972, a further mechanistic possibility, namely the attack by alkyl oxygen, was suggested. In a study of the interaction of the cyclic alkyl ester (64) and the phosphorochloridate (65) the use of l 8 0 labelled compounds and the methanolytic analysis of the resultant mixture of isotopically labelled pyrophosphates showed that the reaction evidently proceeded by each pathway to approximately the same extent.76 Ger. Offen. 2 359 245/1974 (Chem. Abs., 1974, 81, 91 204); Ger. Offen. 2 319 047/1974 (Chem. Abs., 1975, 82, 57 462); N. T. Thuong and P. Chabrier, Bull. SOC.chim. France, 1974, 667. 67 Fr. Demande 2 193 023/1974 (Chem. Abs., 1975, 82,56 871). 68 Y. Okamoto, N . Kimura, and H. Sakurai, Bull. Chem. SOC.Japan, 1974, 47, 1299. 69 K. Maekawa, Y. Shuto, E. Taniguchi, and Y. Miyoshi, Botyu-Kagaku, 1974, 39, 21 (Chem. Abs., 1974, 81, 49 205): K. Kamoshita and Y. Nishizawa, ibid., p. 18 (Chem. Abs., 1974, 81, 49 21 1). 70 0. N . Grishina, M. I. Potekhina, I. A. Elfimova, and S. M. Klyuchanskaya, Neftekhimiya, 1974,14, 905 (Chem. Abs., 1975, 82, 171 150). 7 1 0.N. Grishina, I. P. Lipatova, I. A. Elfimova, and M. I. Potekhina, Neftekhimiya, 1974,14,147 (Chem. Abs., 1974, 81, 4015). 72 M. A. Dzyubina, V. F. Zhurba, N. A. Nechitailo, V. V. Shar, and P. I. Sanin, Neftekhimiya, 1974,14, 652 (Chem. Abs., 1975, 82, 72 501). 73 U.S.P. 3 819 688/1974 (Chem. Abs., 1974, 81, 77 681). 74 Japan. Kokai 74/26 290 (Chem. Abs., 1974, 81, 135 702). Y.Butsugan, K. Kanase, K. Saheki, M. Muto, and T. Bito, Nippon Kagaku Kaishi, 1973,2338 (Chem. Abs., 1974, 80, 59 582). 76 P. Simpson and A. Zwierzak, J.C.S. Perkin I , 1975, 201.
66
5
OrganophosphorusChemistry
118 0
M.;c
0
0
l8O
0
+
‘/P/\ OMe
The details of nucleophilic displacement reactions continue to attract attention. Using model 1,3,2-dioxaphosphorinans,it has been shown that the trans-fluoride (70), obtainable as indicated (Scheme 3), reacts with HO- and MeO- largely with
EP
i5
P-s
P-R
I1
\,/;”
EtO Et’
tmns
S cis
‘x
(66) X = Cl,Br,orF (68b)
(67) R (69) R (71) R (73) R (69)
(68) a; R = Cl b; R (70) R = (72) R = (74) R =
= C1 or Br = F = OMe = OH
(70)
= Br
F OMe OH
84% (72)
+
16% (71)
65% (74)
+
35% (73) Reagents: i, NH4F,MeCN; ii, NH4F; iii, HO-; iv, MeO-
Scheme 3
retention of configuration; this result contrasts with those obtained with the phosphonic halides (66), and with the cis- (67) and trans- (68) phosphorothionohalidates, which react with the same nucleophiles with preponderant, if not complete, inversion of configuration at phosphorus.7 7 This, then, is further evidence that the nature of the leaving group can have some influence on the stereochemical course of a displacement reaction (see ‘OrganophosphorusChemistry’, Vol. 6, p. 105,for other examples). 77
M. Mikolajczyk, J. Kryzywanski, and B. Ziemnicka, Tetrahedron Letters, 1975, 1607.
Quinquevalent Phosphorus Acids
119
The kinetics of hydrolysis of mono-p-iodobenzyl phosphate at pH 1-8,78 of 2-ethylhexyl phosphate in 2-8M-HCl,7B and of the action of alkali and hydroxylamine on Malathion have been determined. Based on the lack of deuterium solvent effect, and the effect of the substituent R, the transition state in the solvolysis of 2-halogenoalkyl phosphoric dianions at various pH's and at 26-50 "C is pictured as somewhat resembling a dipolar ion (Scheme 4). RCHCH,P(O)(O-),
I X
-
[X-eHRC&W,2-]
__f
RCH=CIE,
+ HX + H,PO,
Scheme 4
A detailed study has been made of the hydrolysis of exo-cis- (75) and endo-cis-(76) diphenyl2-(3-~arboxy)norbornylphosphates, following the course of the reaction by spectroscopicmeasurement of [Ph0-].82 Over the pH range 0.97-1 2.6, (77) undergoes solvolysis to diphenyl phosphate and the em-norbornyl cation. This does not appear to be a problem in the case of (75) and (76), and the carboxy-group clearly
(76) R = C0,H (77) R = H
(75)
assists the hydrolysis substantially, although it is difficult to say by precisely how much. The available evidence appears to argue against the intermediacy of the hitherto unknown phosphorane (78). The absolute rates of hydrolysis of (75) and (76) and the extent of catalysis by C02Happroximate to those found for salicyl diphenyl phosphate. The mixed anhydride (79), prepared by ozone oxidation of the tervalent phosphorus compound, hydrolyses about 20 times faster than acetyl dimethyl phosphate, the reaction being complete in about 15 s at 5 "C; this high reactivity probably indicates reaction, viz. attack by water, to be occurring primarily at phosphorus rather than at the carbonyl group. The products are ethylene hydrogen phosphate and
(79)
'8
79
(80) R = Me (82) R = Ph
M. M. Mhala and A. V. Killedar, Current Sci., 1974, 43,465 (Chem. Abs., 1974, 81, 151 192). E. S . Barketov, A. A. Zaitsev, and N. I. Kiiko, Zhur.priklad. Khim, 1974,47,1893 (Chem. Abs., 1975, 82, 42 554).
80 82
V. M. Bhagwat, B. V. Ramachandran, and P. M. Nair, Indian J. Chem., 1974,12, 502. M. J. Gregory and G. M. C. Higgins, J.C.S. Perkin II, 1974, 711. S. S. Simons, jun., J. Amer. Chem. SOC.,1974, 96, 6492.
120
Organophosphorus Chemistry
Under alkaline conditions, the phosphoramidates (80) and (81) hydroacetic lyse about 2 x log times as rapidly as do similar acyclic phosphoramidates. Compound (81) liberates dimethylamine and yields a mixture of propylene cyclic phosphate and the two possible O-hydroxy(iso)propylhydrogen phosphoramidates; (80) also undergoes considerable P-N bond cleavage, but there is no liberation of MeOH, while (82), as expected, hydrolyses almost exclusively at the ring P-0 bond because of the less basic nitrogen and its low apicophilicity relative to oxygen.s4The 1,3,2-0xazaphospholidines from ( - )-ephedrine, and compounds epinieric at phosphorus, undergo ring opening at the P-N bond when allowed to react with sodium methoxide in methanol at room temperature.ss At temperatures up to ca. 320 "C, the O-aryl N-cyclohexyl hydrogen phosphoramidates (83) are converted into the pyrophosphoramidic hydrogen phosphates (84)
in 78-98 % yield; cyclohexylamine (85-95 %) is liberated together with small amounts of other materials. The order of decreasing stability of the starting phosphoramidates is R = But > Me> NOz (the anomalous case) > H > CLse The extent of reaction between O-alkyl O-methyl phosphoramidothionates and amines seems to depend on temperature and on the basicity of the amine. At 130140 "C,the initial reaction is one of isomerization (85)+(86) brought about by the attacking amine, but subsequent reactions all lead to phosphorodiamidic acids 87 (Scheme 5). Esters of metaphosphoric acid and its nitrogen derivatives have long been implicated in phosphorylation reactions but the monomeric compounds have thus far eluded isolation. Pyrolysis of methyl 2-butenylphostonate (87) at 600 "C for 0.02 s releases butadiene and a species which may be trapped in N-methylaniline and for which the MeOPO, structure has been proposed.ss 83
84 85 87 88
R. Kluger and P. Wasserstein, Tetrahedron Letters, 1974, 3451. C. Brown, J. A. Boudreaux, B. Hewitson, and R. F. Hudson, J.C.S. Chem. Comm., 1975, 504. D. B. Cooper, J. M. Harrison, and T. D. Inch, Tetrahedron Letters, 1974, 2697. M. A. Ruveda, E. N. Zerba, R. Podesta, and S. A. de Licastro, Tetrahedron, 1975, 31, 885. B. A. Khaskin, T. G . Rymareva, and N. N. Mel'nikov, Zhur. obshchei Khim., 1974, 44, 1464 (Chem. Abs., 1974, 81, 90 987). C. H. Clapp and F. H. Westheimer, J. Amer. Chem. Soc., 1974, 96, 6710.
Quinquevalent Phosphorus Acids
121
Ri N
MeS ii ‘-MeSH
R’O’
‘NF?
R3
-1
ii (-NR’R:)
(GN)(&N)P(O)OH + (GN)(R’NH)P(O)OR’ Reagents: i, R%N; ii, HNR4a
Scheme 5
In a ‘three-phase’ system consisting of a polymer support carrying reactant (a), solution (b), and polymer support carrying trapping agent (c), when (a) = (88) was treated with 1,3-bis(dimethylarnino)naphthalene in the presence of (c) = (89), suitable work-up afforded the product (90). Since no phosphate transfer occurred when the derivativized support (91) was used, the existence of the monomeric (92) was tentatively proposed as the transferring agent.8D
gCHaq ’‘ OP(O)R,
0
ll
MeOCOCHNHP(NHC, HJ2
NO2
(88) R = NHC,H,, (91) R = NEt,
In a re-evaluation of the possible role of the Elcb mechanism in the alkaline hydrolysis of phosphoramidic esters, the natures of the dependence of kinetics and of 89
J. Rebek and F. Gavina, J . Amer. Chem. SOC.,1975, 97, 1591.
122
Organophosphorus Chemistry
direction of hydrolysis, i.e. P-0 versus P-S bond breakage, have been determined for the series of compounds (93) and (94) with increasing substitution on The phosphoryl series (93 ;X = 0)hydrolyse only 6-10 times faster than the thiophosphoryl analogues; this is in contrast to (95; X = 0 or S), where the rate difference is ca. 400 times, and for which the Elcb mechanism is consistent with the predicted difference in stabilities of the postulated intermediates (96; X = 0 or S).
(9 3)
(94)
(95)
The compounds (94; X = 0 or S) are noteworthy in that loss of Me0 competes with loss of MeS in a nucleophilic displacement reaction, and the series (93) and (94) appear to hydrolyse by the sN2(P) process (see also refs. 138 and 139). The azodiphosphoric ester (97) 91 and the mixed ester (98) 92 undergo Diels-Alder reactions to give the predictable products. (PhO12 P(O)N= NP(O)(OPh),
(PhMeN),P(O)N=NCO,
(97)
Et
(98)
N-Phosphorylated lithamides show a surprising variation in reactivity towards alkylating agents that is out of proportion to the type and complexity of the latter. The phosphoramidate (99) is lithiated initially to give (loo), subsequently giving the di-lithio-derivative formulated as (101). Alkylation of the latter to give (102) occurs, for example, when R = Me,CH and the alkylating agent is dimethyl sulphate; cyclization to the 1,3,2-diazaphospholidines(103) may take place concomitantly, but Li+ Ri
j
Et>(
(EtO),P(O)NH(CH2),NHR1 (99)
+ (EtO),P(O)N(CH,),NHR*
_j.
Li
0
\ Li’
( 1 00)
n
(Et 0),P( 0 ) N R2
91 g2
N R’R2
dX
N. K. Hamer and R. D. Tack, J.C.S. Perkin IZ, 1974, 1184. J. L. Miesel, Tetrahedron Letters, 1974, 3847. R. J. Cremlyn, M. J. Frearson, and D. R. Milnes, J.C.S. Chem. Cumm., 1974, 319.
Quinquevalent Phosphorus Acids
123
with simple alkyl halides the formation of the cyclized products seems to be favoured.O3 The effect of the nature of R on the reactivity of the carbanion from R2P(0)NMeCHaPh was commented upon in last year’s Report; briefly, the anion from the diethoxy-compound undergoes elimination whereas that from the bis(dimethy1amino)-compound is stable. It has now been shown that, predictably, the anion (104)
(104)
/ \
1 Me
is intermediate in reactivity, reacting normally with carbonyl compounds, e.g. benzophenone, at low temperatures, but at ambient temperatures the formation of diazaphospholidinesand oxazaphospholidinesis also to be observed.O4 Primary phosphoramidothionates may be acetylated by acetic anhydride in the presence of BF3 etherate.g6Direct fluorination of dialkyl N-alkylphosphoramidates yields NN-difluoroalkylamines.O6 Under photolytic conditions diethyl NN-dibromophosphoramidate reacts with
(EtO),P(O)NQ
-b (EtO)2P(0)WC~CR?-CR2CH$l
* H
(EtO), P(O)NHCH=CBrPh (105) Reagents: i, CH2=CR1CR8=CHa; ii, Bra; iii, HCI; iv, HO-
Scheme 6 93 O4
O6 96
P. Savignac, G. Lavielle, and M. Dreux, J. Organometallic Chem., 1974, 72, 361. P. Savignac, M. Dreux, and Y . Leroux, Tetrahedron Letters, 1974, 2651; P. Savignac, Y. Leroux, and H. Normant, Tetrahedron, 1975, 31, 877. Japan. Kokai 73/34 583 (Chem. A h . , 1974, 80, 120 244). J. Bensoam and F. Mathey, Comot. rend., 1974,278, C, 1313.
124
Organophosphorus Chemistry
phenylacetylene to give the phosphoramidate (105) ;Q7 the corresponding dichlorophosphoramidate has been employed in a novel synthesis of pyrrolidine derivatives (Scheme 6).98 The bis(dimethy1amino)phosphoryl group has been used for protection in the preparation of 1-bromoalk-2-ynes (Scheme 7).99 (Me,N),P&WCX$=
C-
(Me, N),P( O)OCH,C
is
C(CH,), Me
BrCH.$sC(CHJ,Me Reagents: i, Me(CH2)J; ii, PBr3
Scheme 7
Further study of the action of diphenyl phosphorazidate on malonic half esters in the presence of alcohols has revealed that mixed carboxylic-phosphoric anhydrides may play a part as intermediates in the esterification process.1oo
Synthetic uses of phosphoramides, in particular HMPT, continue to be reported. Alkyl phosphorodiamidates react with keten to give the phosphorus analogue of uracil (1O6).lo1 Other phosphorotriamides have been used for the preparation of carboxamides, the number of amido-groups involved depending on solvent and possibly the reaction temperature.lo2 0
HMPT is a valuable solvent for the carbonylation of Grignard reagents at room temperature and atmospheric pressurelo3and for the reduction of arenes by alkali metals.1o40x0-dihydro-heterocycles are converted by HMPT into the dimethylamino-heterocycle,a process in which the aryl bis(dimethy1amino)phosphate appears 97
T. Gajda and A. Zwierzak, Zeszyty Nauk. Politech. lodz (Chem.), 1974, (29), 108 (Chem. Abs., 1974, 81, 77 598).
A. Zwierzak and T. Gajda, Tetrahedron Letters, 1974, 3383. 99 G. Sturtz, J. P. Parigam, and B. Corbel, Synthesis, 1974, 730. 100 K. Ninomiya, T. Shioiri, and S. Yamada, Chem. and Pharm. Bull. (Japan), 1974, 22, 1795. 1 0 1 M. N. Preobrazhenskaya,V. N. Tolkechev, I. S. Levi, and M. Z . Kornverts, Khim. geterotsikl. Soedinenii, 1974, 1433 (Chem. Abs., 1975, 82, 43 369). 102 A. P. Marchenko, A. M. Pinchuk, and A. G. Feshchenko, Zhur. obshchei Khim., 1974,44, 67 (Chem. Abs., 1974,80,108 141). 103 W. J. J. Sprangers, A. P. van Swieten, and R. Louw, Tetrahedron Letters, 1974, 3377. 104 W. Kotlarek, Tetrahedron Letters, 1974, 3861. 9s
125
Quinquevalent Phosphorus Acids
not to be an intermediate.lo52-Dimethylaminoquinolinesare obtained from acetanilides upon heating with DMF in HMPT.lo6HMPT also converts benzylic type halides alkyl (other than methyl) aryl ketones into into NN-dimethylamino-compounds,107 3,5-dialkyl-2,6-diarylpyridine~,~~~ and benzoins into 2,3,5,6-tetra-arylpyridines.log Thermal treatment of 4-homoadamantol and bicyclo[3,3,l]nonanols with HMPT yields alkenes; should the formation of the latter present difficulties then various types of products may be formed, e.g. 2-adamant01 gives 2-adamantyl bis(dimethy1amino) phosphate, while in other cases complete reductive removal of a hydroxygroup may result.llo As the result of a 15N tracer study, an ANRORC (addition of nucleophile-ring opening-ring closure) mechanism has been proposed for the conversion of oxodihydro-heterocycles into the corresponding amino-heterarenes by the action of phenyl phosphorodiamidate.lll Reactions of Phosphonic and Phosphinic Acid Derivatives.-The P-S-P linkage is broken by the action of bis(dimethylamino)suIphane.112 [Ph,P(S)I 2 s
T''ms
Ph,P(S)S,NMe,
+ Ph,P(S)NMe,
In an interesting transformation, thermolysis of 1-trimethylsilyloxyphosphonates at 160 "C yields silyl phosphites in greater than 80% yield, possibly by the intervention of an equilibrium of the type indicated in Scheme 8.'13
Scheme 8
A detailed study of the action of dibenzylamine on phenylphosphonic and phosphonothioyl dichlorides has been made 114and the preparation and reactions of phosphonylated vinyl ureas have been recorded.l15 Addition of hydroperoxides to E. B. Pedersen and S. 0. Lawesson, Tetrahedron, 1974, 30, 875. B. Pedersen and S. 0. Lawesson, Acta Chem. Scand. ( B ) , 1974, 28, 1045. 107 S. Arimatsu, R. Yamaguchi, and M. Kawanisi, Bull. Chem. SOC.Japan, 1975, 48, 741. lo*R. S. Monson and A. Baraze, Tetrahedron, 1975, 31, 1145. l o o R. S. Monson and A. Baraze, J. Org. Chem., 1975, 40, 1672. 110 S. Arimatsu, R. Yamaguchi, and M. Kawanisi, Bull. Chem. SOC.Japan, 1974, 47, 1693. 111 A. P. Kroon and H. C . Van der Plas, Tetrahedron Letters, 1974, 3201. 112 E. Fluck, G. Gonzales, and H. Binder, Z . anorg. Chem., 1974, 406, 161. 113 A. N. Pudovik, Yu. I. Sudarev, A. P. Pashinkin, V. I. Kovalenko, A. M. Kibardin, and T. Kh. Gazizov, Doklady Akad. Nauk. S.S.S.R., 1974,218,359 (Chem. Abs., 1975,82,43 537); A. N. Pudovik, T. Kh. Gazizov, and Yu. 1. Sudarev, Zhur. obshchei Khirn., 1974, 44, 951 (Chem. Abs., 1974, 81, 13 601). 114 J. D. Healy, R. A. Shaw, B. C . Smith, C. P.Thakur, and M. Woods, J.C.S. Dalton, 1974,1286. 115 V. V. Doroshenko, E. A. Stukalo, and A. V. Kirsanov, Zhur. obshchei Khim., 1974, 44, 69 (Chem. A h . , 1974, 80, 96 092); E. S. Gubnitskaya, I. M. Loseva, and E. A. Stukalo, Khim. Farm. Zhur., 1974, 8, 13 (Chem. Abs., 1975, 82, 43 532). 105
lo6E.
Organophosphorus Chemistry
126
vinylphosphonates1ls and the thermolysis of the products back to alkenes has also been reported.l1 Carboxamides are formed by breakage of the phosphorus-carbon bond during ammonolysis of l-oxophosphonates ;llS such phosphonates also react with dialkyl phosphoramidites when the initial products (107) isomerize on being heated.llB (EtO),P(O)COR' + NH,(1)
-
I(EtO),PNHRa
NR2 (EtO), PH 'OCHRP(0)(OEt)2
+ (EtO),P(O)H
R'CONH, 85-95%
0
i?:
RL,
ph
*
II
EtOP-OCHPhP(O)(OEt),
I
NEtPh
1-Oxophosphonatesalso react with diethyl phosphoroisocyanatiditeat moderately elevated temperatures to give a mixture of the isomeric 1,3,2-0xazaphospholidine derivatives (108) and (109).120 The great interest in the application of organophosphorus chemistry to conventional organic synthesis is further illustrated by the 0
0
11 ,NEt
*'"
II
+
EtOP-N
R2 k:)(OEt,
0
f
(EtO),PNCO R' = Et
(MeO),F(0)oCHPhCONMeCHMeCOPh (110)
Me
,/&.E~,N
Ph
Ger. Offen. 2 342 185/1974 (Chem. Abs., 1974, 81, 13 647).
116 11' 118
Y.Okamoto, T. Kawai, and H. Sakurai, Bull. Chem. SOC.Japan,
119
A. N. Pudovik, E. S. Batyeva, V. D. Nesterenko, and N. P. Anoshina, Zhur. obshchei Khim.,
1974, 47, 2903.
M. Sotoka and P. Mastalesz, Zhur. obshchei Khim., 1974, 44, 463 (Chem. Abs., 1974, 80, 121 058). 1974,44, 1674 (Chem. Abs., 1975,82,4357).
leo I. V.
Konovalova, L. A. Burnaeva, L.S. Yuldasheva, and A. N. Pudovik, Zhur. obshchei Khim., 1974,44,2408 (Chem. Abs., 1975,82,98 071).
Quinquevalent Phosphorus Acids
127
study of the formation of oxazine and azetidine derivatives from 1-oxophosphonates and oxazolium salts, in a sequence of reactions thought to involve the stable intermediate (1 The anions from diethyl ethoxycarbonylmethyl- and cyanomethyl-phosphonates react with aryl isothiocyanates to give the esters (1 11 ;R = C02Et or CN), which are employed to prepare the C-phosphorylated thiazolinediones, benzothiazolines, and pyrazolines.122The sulphonium ylides (112) react as though stabilized by the phosphoryl group. (EtO), P(0)CHRCSNHAr
R~M&-- CHP(O)(ORZ),
(1 11)
(1 12)
Diethyl benzylphosphonatehas been formylated by the action of either t-butoxyNNN'N'-tetramethylmethylenediamine or DMF diethyl a ~ e t a 1 . lChloromethyl~~ phosphonate anions react with trichloromethyl compounds to yield dichloromethylphosphonates (Scheme 9).125Interestingly, although yields from this reaction are generallygood, e.g. for (1 13 ;R1R2 = MeNCH2CH2NMe),the bis(dimethy1amino)compound (113; R1 = R2 = NMe,) fails to give any dichloromethyl product. anion
R~R~P(O)CH,CI
R~R~P(O)CHCI,
(113)
X = Cl, CO,Me, or CONMe, Reagents: i, BuLi-THF, -78 "C;ii, CCbX
Scheme 9
An ionic mechanism has been proposed for the first reported isomerization of an allylic (phosphonate) ester (114) to (1 1 9 , and vice uersa.126 0
0
I1 PhP-OCH,CH=CHMe I
II tz * PhP--OCHMeCH=CQ I
OH
OH (1 14)
(115)
In the nitration of 2-methoxybenzenephosphonic acid, nitration occurs predictably meta to the phosphoryl group and both ortho- and para-to the methoxy-group, but nitrodephosphonation also takes pla& to a small extent (ca. 3%).12' The increasing order of effectivenessof the catalysts RPCl, for use in the isomerization of the phosphinic chloride (1 16) to (1 17) is TiCI, < SnCI, < PCl, < ZnC12.128 The composition of the final product obtained by interaction of diethyl hydrogen A. Takamizawa and H. Sato, Chem. and Pharm. Bull. (Japan), 1974, 22, 1526. G. Barnikow and G . Saeling, J. prakt. Chem., 1974, 316, 534. lZ3K. Kondo. Y. Liu, and D. Tunemoto, J.C.S. Perkin I, 1974, 1279. 124 M. A. Grassberger, Annalen, 1974, 1872. 125 P. Savignac, M. Dreux, and P. Coutrot, Tetrahedron Letters, 1975, 609. 126 A. W. Herriott, J. Org. Chem., 1975, 40, 801. 127 T. Modro and A. Piekos, Phosphorus, 1974, 3, 195. 128 B. A. Arbuzov, A. 0. Vizel, R. S. Giniyatullin, L.I. Schukina, and T. A. Zyablikova, Phosphorus, 1974, 4, 39. 121 122
Organophosphorus Chemistry
128
(116)
(117)
phosphonate and the phosphine oxide (118) has been rationalized in terms of an initial addition reaction to give (1 19), from which diphenylphosphine oxide is eliminated prior to further addition of diethyl hydrogen phosphonate, to give (120) .I2@
(EtO),P(O)NPhCHPhP(O)(OEt), (120)
The oxidation of (p4odophenyl)phenylphosphinicacid with persulphuric acid to the iodoso-acid and treatment of the iodonium bromide with alkali yields a betaine, probably (121); the ortho-isomer of the phosphinic acid gives the cyclic compound (122).130
\
0 (121)
OH
(122)
Hydrolysis of the phosphonobenzanilide (123) yields the corresponding phosphonocarboxylicacid and aniline. At pH 6 the reaction of the monoanion of (123) is ca. 6 x lo5 times faster than that of benzanilide itself; the postulated intermediate (124) is already known to hydrolyse rapidly under similar experimental conditions.131 Further study of the rearrangement of Dipterex (125) to the enol phosphate (126) has demonstrated the difficulties caused by subsequent hydrolysis of the latter to dichloroacetaldehydeand thence to glyoxal in the detailed analysis of the mechanistics. The initial step, prior to rearrangement, is first-order with respect to the acidbase equilibrium in the pH range 8-12; further hydrolysis of (126) is first-orderwith respect to each of (126) and HO-.132The presence of an unionized intermediate has been established, the positive activation entropy being a strong indication of the intramolecular character of the rearrangement, which probably occurs through a three-centre r e a ~ t i 0 n . l ~ ~ In 0.02N-HCl, the esters (127) hydrolyse at both the P--S and P-0 12@ 130 13l 132
133 134
H. Gross, B. Costisella, and L. Brennccke, Phosphorus, 1974, 4, 241. L. D. Freedman and R. P. DeMott, Phosphorus, 1974, 3, 277. R. Kluger and J. L. W. Chan, J. Amer. Chem. SOC.,1974, 96, 5637. N. Yuksekisik, Comm. Fnc. Sci. Univ. Ankara, 1973, 20B, 49 (Chem. A h . , 1974, 81, 62 748). G. Aksnes and N. Yuksekisik, Phosphorus, 1974, 4, 33. V. E. Bel'skii, N. N. Naberezhnova, A. G . Abul'khanov, and B. E. Ivanov, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1974, 2864 (Chem. Abs., 1975, 82, 85 682).
129
Quinquevalent Phosphorus Acids
L
ap(o '
@leO)zP(0)CHOHCC&
-OH*
(h4eO),P(O)OCH=CCL,
(125)
-+
CO,H
CHC4CHO -+ (OHC),
(126)
(EtO),P(0)R'R2 (127) RW = Me, SEt; OEt, SEt; or SMe, OEt
Me(EtO)P(O)SC,&NR, (128)
(compare ref. go), although for the ester (128), at pH < 7 and pH > 10, only breakage of the phosphorus-sulphur bond was observed, while at pH 7-10 the mode of cleavage depended on R.136 Diallylphosphinic esters (129) hydrolyse in dilute KOH solutions at 15-98 "C predominantly by an S ~ Z t y p mechanism.136 e The phosphinic amides (130a) form stable hydrochlorides in dilute HCl at room temperature, but the amides (130b), where there is less steric interference, hydrolyse to ammonium ch10ride.I~' (C&=CHCH,),
P(0)OR
(129)
b; R = Et or (130)
With increasing frequency, results are appearing which do not appear to conform to the currently accepted ideas regarding mechanisms of displacement reactions, particularly with regard to the involvement of pentaco-ordinate intermediates. This appears to be the case for the alkaline hydrolysis of some phosphonothioate esters. Unlike the salt (131), which, with alkali, loses MeS- with essentially complete retention of configuration at phosphorus, 0-menthyl S-methyl phenylphosphonodithioate 135
J. Epstein, J. J . Callahan, and V. E. Bauer, Phosphorits, 1974, 4, 157.
lS6
A. I. Razumsv, I. A. Krivosheeva, B. G. Liober, T. A. Tarzivolova, Z. M. Kharnmatova, and V. A. Pavlov, Zhur. obshchei Khiin., 1974, 44, 51 (Chem. Abs., 1974, 80, 119 307). M. J. P. Harger, J.C.S. Perkin I, 1975,514; M. J. P. Harger, A. J. Macpherson, and D. Pickering, Tetrahedron Letters, 1975, 1797.
13'
130
0rganophosphorus Chemisf r y
(1 32) hydrolyses with predominant inversion of configuration; according to the accepted rules, this reaction should proceed with kinetic preference for axial attack opposite RO through (133); however, the displacement of MeS- with inversion at phosphorus is inconsistent with this structure in that retention of configuration would be required. The authors therefore fall back on an explanation in terms of a normal S~2(P)-typedisplacement that is dependent on the concentration of HOand which proceeds through (134).138(See also ref. 90.) Ph\
Me
\\I”
/ \ Ro SMe
SbCG
(131)
(133)
R = Menthyl The alkaline hydrolysis of 0-menthyl S-methyl methylphosphonodithioate also proceeds with predominant inversion at phosphorus, and the speed of reaction is independent of the concentration of HO-. Bearing in mind the previously reported racemizations of S-phenyl and S-isopropyl 0-isopropyl methylphosphonodithiolates in the presence of a large excess of base, the present results are difficult to explain.139 The mathematical solution of the kinetic equations for the interaction of 1phenylbutane-l,2,3-trione-Zoxime with 0-isopropyl methylphosphonofluoridate and the breakdown of the product requires the use of an analogue Studies have been carried out on the 1,3-dipolar cycloaddition of phosphoruscontaining diazoalkanes to activated alkenes 141 and on the reactions of ethynylphosphonates with phenyl a ~ i d e land * ~ with ethyl diaz0a~etate.l~~ Other reports deal with the addition of CN- to 1-cyanovinylphosphonicesters,144the preparation and and the transformations of 1-hydroxyproparproperties of 1 -diazophosph~nates,~~~ gylphosph~nates.~~~ K. E. DeBruin and D. M. Johnson, Phosphorus, 1974, 4, 13. K. E. DeBruin and D. M. Johnson, Phosphorus, 1974,4, 17. B. W. Ford and P. Watts, J.C.S. Perkin 11, 1974, 1009. A. N. Pudovik and R. D. Gareev, Zhur. obshchei Khim., 1974,44,1432 (Chern. Abs., 1974,81, 151 335). 142 A. N. Pudovik, N. G. Khusainova, E. A. Berdnikov, and 2. A. Nasybullina, Zhur. obshchei Khim., 1974, 44,222 (Chem. Abs., 1974, 80, 107 635). 143 A. N. Pudovik, N. G. Kushainova, and T. V. Timoshina, Zhur. obshchei Khim., 1974, 44, 272 (Chem. A h . , 1974, 80, 121 067). 144 D. Danion and R. Carrie, Bull. SOC.chim. France, 1974, 1535. 145 U. Felcht and M. Regitz, Chem. Ber., 1975, 108, 2040. 146 M. G . Zimin, A. A. Sobanov, and A. N. Pudovik, Zhur. obshchei Khim., 1974,44,2582 (Chern. Abs., 1975, 82, 43 534).
13* 139 140 141
7 Phosphates and Phosphonates of Biochemical Interest BY D. W. HUTCHINSON
1 Introduction The application of magnetic resonance techniques to the study of enzymes has attracted considerable interest in the past year; for example, the binding of a substrate to an enzyme can be studied by these means. Work has continued on the purification of enzymes by affinity chromatography, although few new organophosphorus compounds have been developed for this purpose. Another topic of importance has been the study of isoprenoid phospholipids; several have now been isolated from animal and bacterial sources, and it is now realized that these phospholipids play an important role in the biosynthesis of glycoproteins. The latest volumes in the series ‘Methods in Enzymology’l and ‘The Enzymes’2 have appeared in the past year and both series contain a number of articles on phosphates and phosphonates of biochemical interest. 2 Coenzymes and Cofactors Nicotinamide Nuc1eotides.-The synthesis and properties of NAD+ analogues have been reviewed, with particular emphasis on the modification of amino-acids at the active sites of dehydrogenases by these compounds. 3-Aminopyridine-adenine dinucleotide (1) can be prepared from NAD+ by the Hofmann hypobromite reaction and is a coenzyme competitive inhibitor of several dehydr~genases.~ Diazotized (1) will modify four SH groups per molecule of enzyme during the complete inactivation of yeast alcohol dehydrogenase.s The reaction of diazonium salts with mercaptogroups in proteins is unusual as tyrosine residues are preferentially attacked in the majority of cases. However, the enzyme is inactivated by other mercapto-specific reagents, and isolation of S-(3-pyridyl)cysteineon degradation of the enzyme after it had been deactivated by diazotized (1) confirms the presence of SH groups near the active site of the enzyme. A spin-labelled derivative (2) of NAD+ with a 2,2,6,6tetramethylpiperidin-4-yl-l-oxy-radical attached to N-6 of the adenine residue has been prepared by condensing the corresponding adenosine mononucleotide with NMN+ in the presence of DCC.g The radical (2) functioned as a coenzyme for a ‘Methods in Enzymology’, ed. S. P. Colowick and N. 0. Kaplan, Academic Press, New York, 1974-75, VOlS. 34-38. 2 ‘The Enzymes’, ed. P. D. Boyer, 3rd Edn., Academic Press, New York, 1974, Vols. 9, 10. C. Woenckhaus, Topics Cwrent Chern., 1974, 52, 209. 4 T. L. Fisher, S. V. Vercellotti, and B. M. Anderson, J. Biol. Chem., 1973, 248, 4293. J. K. Chan and B. M. Anderson, J. Biol. Chem., 1975, 250, 67. 13 W. E. Trommer, H. Wenzel, and G. Pfleiderer, Annalen, 1974, 1357. 1
131
Organophosphorus Chemistry
132
I
R'
I
R' (3) R' = adenosine 5 '-pyrophosphoryl-5-(p-D-ribofuranosyl) R' = nicotinamide ~-~-ribofuranosyl-5-pyrophosphoryl-S'-(~-~~-ribofuranosy1)
number of dehydrogenases and whereas its e.s.r. spectrum in solution consisted of a triplet with fine-structure, when the radical was bound to an enzyme the spectrum broadened to one corresponding to an immobile radical. An analogue of NAD+ in which the adenine moiety has been replaced by 3,N4-ethenocytosine(EC)has also been prepared by the condensation of NMN+and ECMPin the presence of DCC.' The coenzyme analogue (eNCD+)(3) had coenzyme activity in a number of enzyme systems and was more active than nicotinamide 1 ,N6-ethenoadeninedinucleotide (ENAD+) (4). The relatively high coenzymic activity of (3) may be due to the stereochemical similarity between No-substituted adenine and N1-substituted 3,N4ethenocytidine residues. Hence NAD+ and (3) should occupy a similar amount of space in the active site of an enzyme. NAD+has been attached to an insoluble support either through the N-6 atom of the adenine by means of an N-(6-aminohexyl)acetamido-group8a or with the aid of 6-aminocaproic acid and DCC.BbIn the latter case the NAD+ is presumably also attached through the N-6 of the adenine moiety. An enzyme electrodeg has been described involving immobilized NAD+, lactate dehydrogenase, and glutamate dehydrogenase.8a This coupled system has been used to determine glutamate concentrations of the order of to moll-l. Treatment of NADP+ or NADPH at 100 "C under mildly alkaline conditions resulted in the formation of a triphosphate of adenosine.lo Chemical and enzymic analysis proved this to be 2'-phosphoadenosine 5'-diphosphate, and an intermediate J. C . Greenfield, N. J. Leonard, and R. I. Gumport, Biockemistry, 1975, 14, 698. (a) P. Davies and K. Mosba-ch, Biochim. Biopltys. Acra, 1974, 370, 329; (b) A. K. Grover and G. G. Hammes, Biochim. Biophys. Actn, 1974, 356, 309. D. A. Gough and J. D. Andrade, Science, 1973, 180, 380. lo C . Bernofsky, Arch. Biocltem. Bioplzys., 1975, 166, 645.
133
Phosphates and Phosphonates of Biochemical Interest
in this hydrolysis appears to be 2’-phosphoadenosine 5’-diphosphate ribose. Thus, this hydrolytic breakdown of NADP+ is similar to that already observed for NAD+.ll Flavin Coenzymes.-The structure of the oxidized form of flavodoxin from a strain of Clostridium has been determined at 1.9 A resolution by X-ray crystallography.l* The phosphate group of a flavine mononucleotide (FMN) residue, the prosthetic group of the flavoprotein, is surrounded by four hydroxyl-containing amino-acids and there are also four backbone NH groups in its vicinity. Hydrogen-bonding between these OH and NH groups and the phosphate may account for the high free energy of association with flavodoxin of FMN compared with riboflavin. The FAD of the flavin prosthetic group of Chromatiurncytochrome c is linked through the 8 ~ position to a cysteinyl residue (5).13 The amino-acid sequence in this region of the protein is Tyr-Thr-Cys(FAD)-Tyr and there is a marked interaction between the Nterminal tyrosine of the peptide and the flavin moiety of the FAD. This may be an important factor in stabilizing the thiohemiacetal bond in (5).14 CH
( 5 ) R = adenosine 5’-pyrophosphoryl-5-ribityl
(6)
Pyridoxd Phosphates.-The 31P n.m.r. spectra of pyridoxal or pyridoxamine phosphates consist of a single resonance coupled to the 5’-methylene group,16and single resonances are still observed in the n.m.r. spectra of pyridoxal or pyridoxamine phosphates when they are bound to aspartate transaminase. These resonances correspond to those observed with the fully ionized compounds and it appears that the phosphate group is held in a positive region in the holoenzyme by ionic forces rather than by covalent bonding to a threonine residue.ls The apoenzyme contains a region of high selectivity for phosphates and has a high affinity for inorganic phosphate. The latter is, however, displaced by pyridoxal phosphate during formation of the holoenzyme. 4’-Ethynyl-4’-deformylpyridoxalphosphate (6) can be prepared by phosphorylating the corresponding alcohol with a mixture of phosphoric oxide and phosphoric acid.17 Both (6) and the 4’-vinyl analogue are bound to the apoenzyme in their dipolar ionic forms, confirming the evidence obtained by 31P n.m.r. that there is a positive region near the active site of the enzyme. l1 S. P. Colowick, N. 0. Kaplan, and M. Ciotti, J. l2 R. M. Burnett, G. D. Darling, D. S. Kendall, M.
Biol. Chem., 1951, 191, 447. E. Le Quesne, S. G. Mayhew, W. M. Smith, and M. L. Ludwig, J. Biol. Chem., 1974,249, 4383. l3 W. H. Walker, W. C. Kenney, D. E. Edmondson, and T. P. Singer, European J. Biochem., 1974, 48, 439. l4 W. C . Kenny, D. E. Edmondson, and T. P. Singer, European J. Biochem., 1974, 48, 449. l5 M. Martinez-Carrion, European J , Biochem., 1975, 54, 39. l6 R. M. Khomutov, E. S. Severin, E. N. Khurs, and N. N. Galayaev, Biochim. Biophys. A d a , 1969, 171, 201. l7 I . Y . Yang, C. M. Harris, D. E. Metzler, W. Korytnyk, B. Lachmann, and P. P. G. Potti, J. Biol. Chem., 1975, 250, 2947.
134
OrganophosphorusChemistry
Immobilized derivatives of pyridoxal phosphate have been prepared in which the coenzyme is joined to the support through nitrogen (7),18 oxygen (8),18 or carbon
(9).lD All three derivatives could be used to immobilize apotryptophanase and hence should be useful for the purification of pyridoxal-requiring enzymes by affinity chromatography.
3 Sugar Phosphates 2-Deoxy-~-ghcose(10) will inhibit a number of animal viruses by depressing the synthesis of viral glycoproteins at concentrations which do not interfere with the energy supply of the host cells.2oIt has recently been shown2' that when I4C-labelled (10) is administered to chick-embryo fibroblast cells in tissue culture, a number of its phosphorylated derivatives are formed. These include the 1- and 6-monophosphates,
l* l9
S. Ikeda, H. Han, and S. Fukui, Biochim. Biophys. Acta, 1974, 372, 400. S. Ikeda and S. Fukui, Biochem. Biophys. Res. Comm., 1973, 52, 482.
2o
G. Kaluza, M. F. G . Schmidt, and C. Scholtissek, Virology, 1973, 52, 447. M. F. G . Schmidt, R. T. Schwarz, and C. Scholtissek, European J . Biochem., 1974, 49,237.
21
135
Phosphates and Phosphonates of Biochemical Interest H O T H 2 O 3 P 0 /OH
@ OH NHAc
H,O,PO
HO OH (12)
(1 3)
the 1,&diphosphate, UDP-2-deoxy-~-glucose(UDPdGlc), and GDPdGlc. Since (10) and 2-deoxy-~-mannoseare identical, the formation of GDPdGlc is not unexpected since it is the analogue of GDPMan. The chemical synthesis of the extremely acidlabile UDPdGlc has been achieved by the phosphoromorpholidate method.22 Whereas epimerization of UDPdGlc to UDPdGal occurred with enzyme extracts from yeast, liver, and plants, no epimerization was observed with the chick cells. The oxidation of a variety of metasaccharinic acid phosphates, e.g. (1l), by chlorate in the presence of a vanadium oxide catalyst has been reported 23 and phosphorylated sugars which have been synthesized in the past year include the 4-phosphates (12)24
1
i. iii, ii
1
iv
v,
OH (17) Reagents: i, (MeO),POH; ii, H,O+; iii, H,-Pd; iv, NaCH[P(O)(OEt),I,;
V,
NaOEt
Scheme 1
23 24
T. N. Druzhinina, Y . Y. KUSOV, V. N. Shibaev, N. K. Kochetkov, P. Biely, S. Kucar, and S. Bauer, Biochim. Biophys. Acta, 1975, 381, 301. F. Trigalo, W. Jachymczyk, J. C. Young, and L. Szab6, J.C.S. Perkin I , 1975, 593; F. Trigalo and L. Szab6, ibid., p. 598; F. Trigalo, M. Level, and L. Szab6, ibid., p. 600. F. Trigalo and L. Szab6, J.C.S. Perkin I , 1975, 604; A. Chiron and L. Szab6, ibid., p. 603.
136
Organophosphorus Chemistry
and (13).25 Fully blocked aldoses, e.g. 2,3 :4,5-di-O-isopropylidene-~-xylose, react with dimethyl phosphite to give or-hydroxy-phosphonates(15).2s A variation of this synthesis to yield a-amino-phosphonates involves the preliminary formation of a Schiff base (16) with benzylamine followed by the addition of the ph~sphite.~' Treatment of (14) with phosphonate carbanions, e.g. NaCH[P(O)(OEt)J,, gave rise to olefinic sugar phosphonates(1 7), 28 which underwent base-catalysed rearrangement to (18) (Scheme l).29Ketoses were formed from the latter by acid hydrolysis. Photolysis of glucose 6-phosphate in aqueous solution resulted in the release of orthophosphate. Dehydrogenation and carbonxarbon bond cleavage also took place,3O and an ultraviolet-absorbing compound was an intermediate in this reaction. 6-Phosphogluconate was converted into an arabinose phosphate on photolysis, suggesting that the former could be an intermediate in the conversion of glucose 6-phosphate into arabinose 5-phosphate. 4 Phospholipids Isoprenoid Lipids.-The enzymatic transfer of sugars, e.g. mannose, from nucleoside diphosphate sugars to dolichyl phosphate (19; R = H) has been demonstrated r
1
Me
0
with preparations from a variety of animal cells, including liver,s1 pancreas,32and This sugar transfer appears to be an important step in the human lympho~ytes.~~ biosynthesis of glycoproteins in animals and also in yeasts.34Hydrolytic studies with rnannosidases reveal that the mannolipid of calf pancreas contains ,%linkedmannosyl residues.35 A membrane-associated sialyltransferase from Escherichia coli will catalyse the transfer of N-acetylneuraminic acid from cytidine 5'-monophospho-Nacetylneuraminicacid to undecaprenyl phosphate.3sHere again, a glycosyl phospholipid seems to be an obligatory intermediate in the biosynthesis of glycoproteins. P1-Dolichyl-P2-cc-D-mannopyranosy1 pyrophosphate (19; R = or-D-mannopyranoD. R. Bundle and H. J. Jennings, Canad. J. Biochem., 1974, 52, 723. H. Paulsen and H. Kuhne, Chem. Ber., 1974,107,2635; H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1229. s7 H. Paulsen and H. Kuhne, Chem. Ber., 1975,108, 1239. H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1732. z9 H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1745. 30 C. Triantaphylides and M. Halmann, J.C.S. Perkin ZI, 1975, 34. s1 D. A. Vessey and D. Zakim, European J. Biochem., 1975, 53, 499. 32 J. S. Tracz, A. Herscovics, C . D. Warren, and R. W. Jeanloz, J. Biol. Chem., 1974, 249, 6372. 33 A. Herscovics, C. D. Warren, R. W. Jeanloz, J. F. Wedgwood, L. Y . Liu, and J. L. Strominger, F.E.B.S. Letters, 1974, 45, 312; J. F. Wedgwood, J. L. Strominger, and C. D. Warren, J. Biol. Chem., 1974, 249, 6316. 34 C. B. Sharma, P. Babczinski, L. Lehle, and W. Tanner, European J. Biochem., 1974, 46, 35. 35 J. S. Tkacz and A. Herscovics, Biochem. Biophys. Res. Comm., 1975, 64, 1009. 36 F. A. Troy, I. K. Vijay, and N. Tesche, J. Biol. Chem., 1975, 250, 156. 25
26
Phosphates and Phosphonates of Biochemical Interest
137
syl phosphoryl) has been synthesized from dolichyl phosphate and a-D-mannose-1phosphate with the aid of diphenyl pho~phorochloridate.~~ A similar method has been used to prepare P1-dolichyl-P2-chitobiosepyrophosphate from chitobiose-lp h o ~ p h a t eIn . ~ human ~ lymphocytes the dolichyl chitobiose pyrophosphate transfers its carbohydrate residues to an oligosaccharide containing at least four monosaccharide residues, one of which is mannose. GDP-mannose is a mannosyl donor to the dolichyl chitobiose pyrophosphate but D-mannosyl dolichyl phosphate is not, perhaps due to differences in the anomeric configuration of the mannose residues. Lipoteichoic acids, which are essential components of the membranes of GramFor example, intravenous positive bacteria, can also function as surface injection into rabbits of whole bacterial cells which contain membrane lipoteichoic acids, e.g. certain strains of Lactobacillus, produced an immunogenic response. Incubation of myoinisotol 1-phosphate synthetase with NAD+ and glucose &phosphate, followed by reduction of the product with tritiated borohydride, gave isotopically labelled scyllo- and myo-inositol 1-phosphates(21).40This has been taken as evidence that myoinos-2-ose 1-phosphate (20) was an intermediate in this reaction. In eukaryotes, breakdown of phosphatidyl inositol produces (21), myoinositol 0
Hop "V II
0-P-OH
OH iio
OH (20)
OH
(21)
OH
(22)
1,Zcyclic phosphate (22), and a 1,2-diacyl glycerol. Phospholipase 'c' from Bacillus cereus also cleaved phosphatidyl inositol to liberate (22), revealing hitherto unsuspected cyclizing properties of the enzyme.41 Trimethylsilylation of phospholipids enables them to be separated and isolated by gas-liquid chromatography,42 and this technique has been applied to the analysis of (21) and (22) in rat-brain preparations. About one-third of the non-deacylatablephospholipids in Saccharomyces cerevisiae have been shown to be sphingolipids which contained a single phosphoinositol moiety.43The major inositol phospholipid could be cleaved quantitatively by alkali to give an inositol monophosphate and could be cleaved by periodate to a C,, fragment. These and other data suggest that the phosphoinositol was attached to position 1 of a hydroxysphingamine, and hence the lipid had the structure (23), although the configuration of the inositol has yet to be determined. By similar techniques, a di(inositoLphosphory1)ceramidewas identified in Neurospora c r a ~ s a . ~ ~ C. D. Warren and R. W. Jeanloz, Biochemistry, 1975, 14, 412. J. F. Wedgwood, C. D. Warren, R. W. Jeanloz, and J. L. Strominger, Proc. Nat. Acad. Sci., U.S.A., 1974, 71, 5022. 39 A. J. Wicken and K. W. Knox, Science, 1975, 187, 1161. 40 C. H.-J. Chen and F. Eisenberg, jun., J . Biol. Chem., 1975, 250, 2963. 41 R. H. Michell and D. Allan, F.E.B.S. Letters, 1975, 53, 302. 42 A. L. Majumder and F. Eisenberg, jun., Biochem. Biophys. Res. Comm., 1974, 60, 133. 43 S. W. Smith and R. L. Lester, J . Biol. Chem., 1974, 249, 3395. 44 R. L. Lester, S. W. Smith, G . B. Wells, D. C. Rees, and W. W. Angus, J. Biol. Chem., 1974,249, 37 38
3388.
138
Organophosphorus Chemistry 0
Inositol-0-
I1 I HO
CH- (CH2),,-
P -WH2- CH -CH-
I NH I
CH,
l l OH OH
(2 3)
The transfer of phospholipids between membranes has been reviewed 45 and the distribution of phospholipids in vesicle bilayers has been studied by lH n.m.r.46and 31Pn.m.r.46s47The most important factors which determine the distribution of phospholipids in bilayers are their charge and packing properties. A paramagnetic quenching agent consisting of manganese rather than lanthanide ions has been used in the 31Pn.m.r. study of serum high- and low-density lipoprotein^.^^ Manganese ions were superior to lanthanides in these systems due to the low solubility of lanthanide phosphates in water. From its 31Pn.m.r. spectrum, cardiolipin (24) possesses two non-equivalent phosphorus atoms, and it has been postulated that this is due to differences in hydrogen bonding.49However, the two phosphorus atoms are metabolized at different which is surprising if the only difference between the two atoms was their hydrogen bonding. These observations have recently been rationalizeds1by examining the diasteropticity of (24), from which it was apparent that the two phosphorus atoms are in different environments owing to symmetry considerations rather than hydrogen bonding. 0
HO
5 Naturally Occurring Phosphonates TrisCtrimethylsilyl)phosphite (25) 52 has been used in an elegant synthesis of acidlabile phosph~nolipids.~~ The nucleophilicity was comparable with other trialkyl 45 46 47
48
K. W. A. Wirtz, Biochim. Biophys. Acta, 1974, 344, 95. J. A. Berden, R. W. Barker, and G. K. Radda, Biochim. Biophys. Acta, 1975, 375, 186. J. A. Berden, P. R. Cullis, D. I. Hoult, A. C . McLaughlin, G. K. Radda, and R. E. Richards, F.E.B.S. Letters, 1974, 46, 55. T. 0. Henderson, A. W. Kruski, L. G. Davis, T. Glonek, and A. M. Scanu, Biochemistry, 1975, 14, 1915.
49 50 51 52
53
T. 0. Henderson, T. Glonek, and T. C . Myers, Biochemistry, 1974, 13, 623. D. C. White and A. N. Tucker, J. Lipid Res., 1969, 10, 220; S. A. Short and D. C. White, J. Bacteriol., 1970, 104, 126; A. N. Tucker and D. C. White, ibid., 1971, 108, 1058. G. L. Powell and J. Jacobus, Biochemistry, 1974, 13, 4024. N. F. Orlov, B. L. Kaufman, L. Sukhi, L. N. Slesar, and E. V. Sudalcova, Khim. Prakt. Prim. Kremniiorg. Soedin., Tr. Sovesch., 1966, 111 (Chem. Abs., 1970, 72, 21 738). A. F. Rosenthal, L. A. Vargas, Y. A. Isaacson, and R. Bittman, Tetrahedron Letters, 1975,977.
Phosphates and Phosphonates of Biochemical Interest
139
phosphites normally employed in the Arbusov reaction, and the trimethylsilyl groups were hydrolysed with ease (aqueous tetrahydrofuran). Phosphonocephalins have been prepared from the correspondingalcohol and (2-phthalimidoethyl) phosphonomonochloridate (26), the phthalimido-group being removed with hydrazine at the end of the synthesis.64The stability of (26) in this reaction is remarkable, particularly
as the phosphonylation was carried out in the presence of triethylamine, a base which should encourage the intramolecular decomposition of (26). A similar phosphonomonochloridate (27)has been reported as being used in the synthesis of O-(2-aminoethyl)phosphono-~-serine.~~ 2-Aminoethylphosphonic acid (28) has been isolated from the lipid fractions of a number of sources, including oysters.6eHowever, it has also been suggested that (28) and other aminophosphonicacids could also be constituents of polypeptide chains.s7 Peptide analogues which contain P-N bonds [e.g. (29)16*would not be stable at pH < 5;69 however, these peptides might be stable under physiological conditions, particularly in a hydrophobic environment. The carboxy-amide (30) 6o was comparatively stable, and such a group could be present in living organisms as a Pterminal phosphonopeptide. 0
II IfiH,CH2CH2P -0I
OH
(28)
0
0
I1
ll I?H3CH2P-NHCHRC0,H I 0-
fiH3CHRCONHCH2CH2P-0-
(29)
(30)
I
OH
6 Oxidative Phosphorylation A chemiosmotic molecular mechanisms1 for ATP synthesis coupled to a proton gradient across a membrane has provoked criticisms2~s3 and a reply.64One of the points of contention is how the ATPase reaction (1) could be reversed (2) by a high
58
E. Baer, Canad. J. Biochem., 1974, 52, 570. E. Baer and J. T. Eber, Canad. J. Biochem., 1974,52, 718. T. Matsubara, Biochim. Biophys. Acta, 1975, 388, 353. L. D. Quin, Topics Phosphorus Chem., 1967,4, 23. M. Hariharan and A. E. Martell, Synthesis Comm., 1973, 3, 375.
59
L. Zervas and P. G. Katsoyannis, J. Amer. Chem. SOC.,1955,77,
54 55 56 57
5351.
M. Hariharan, R. J. Motekaitis, and A. E. Martell, J. Org. Chem., 1975, 40, 470. P. Mitchell, F.E.B.S. Letters, 1974, 43, 189. 62 P. D. Boyer, F.E.B.S. Letters, 1975, 50, 91. 63 R. J. P. Williams, F.E.B.S. Letters, 1975, 53, 123. 64 P. Mitchell, F.E.B.S. Letters, 1975, 50, 95. 6o
140
Organophosphorus Chemistry
concentrationof protons. From thermodynamicconsiderations,local rather than bulk increases in charge in the membrane appear to be the more likely.s3Evidence has ATP2- + H2Q ADPPi(1) ADP- + HPi+ +ATP + HzQ (2)
+
__+
been obtained 65 which, it is claimed, supports the hypothesis 6 6 that energy input in oxidative phosphorylation causes the release of ATP formed at the catalytic site by reversal of hydrolysis (Scheme 2). It is postulated that little or no energy is required to E + ADP
+
,ADP
Pi
E\
Pi
11 energy-linked
E-ATP c L o r m a t i o n a l c E'-ATP + H,O loose complex changc tight complex
\E + ATP
where E is a catalytic site for ATP formation on the mitochondrial membrane Scheme 2
release the ATP. This occurs by a conformational change at the catalytic site on the mitochondrial membrane. An analogue of ATP, adenylyl imidodiphosphate, interacts competitively with the ATPase of mitochondria to inhibit the hydrolytic reaction67 but does not appear to affect the oxidative phosphorylation of whole mitochondria or submitochondrialparticles. The use of analogues of ATP, including thio-derivatives,6 8 could provide valuable information on the processes involved in oxidative phosphorylation. There has only been one papers9 of note in the past year on possible chemical intermediates involved in oxidative phosphorylation. This was concerned with the possible participation of phosphorylated sulphonium salts as phosphorylatingagents. When thianthrene perchlorate, Th+*(31), an aromatic cation radical, was added to a
(31) Th" 65
R. L. Cross and P. D. Boyer, Biochemistry, 1975, 14,392.
66
P. D. Boyer, R. L. Cross, and W. Momsen, Proc. Nat. Acad. Sci. U.S.A., 1973, 70, 2837.
67
R. L. Melnick, J. Tavares de Sousa, J. Maguire, and L. Packer, Arch. Biochem. Biophys., 1975, 166, 139. F. Eckstein, Angeiv. Chem. Internat. Edn., 1975, 14, 160. R. S. Glass, E. B. Williams, jun., and G . S. Wilson, Biochemistry, 1974, 13,2800.
68 69
Phosphates and Phosphonates of Biochemical Interest
141
mixture of AMP and orthophosphate in a dipolar aprotic solvent, ADP and ATP were formed in high yield. Similar results were obtained when 2,3,7,8-tetramethoxythianthrene diperchlorate (32) was used in place of (31). Thus (31) and (32) could be regarded as models for a biological system in which a thiol is oxidized to a cation before participating in phosphoryl transfer (Scheme 3).
- -
2Th"
Pi + Th2+ Th'-0-P(O)(OH),
Th + Th2+
Th+-O-P(O)(OH),
+ AMP
Th'-O-
+ ADP
Scheme 3
7 Enzymology Phosphoproteins.-More evidence has been accumulated of the participation of phosphoproteins in a number of cellular functions, and this topic has now been reviewed.70 For example, acetate kinase from E. coli contains a y-phosphorylated glutamate residueY7lpig-liver pyruvate kinase contains a phosphopeptide in which the phosphate is joined to a serine residue,72and evidence for a phosphohistidinein a phosphotransferasein Staphylococcus has been obtained.73 Phospholipoproteinshave not been found so widely ;however, Bacilluslicheniformis749/C containsa membranebound penicillinase which is a phospholipoprotein.74 The phosphatidyl residue in this enzyme is attached to the protein chain through the alcohol function of a serine residue which is at the N-terminal end of the protein. Certain organophosphorus compounds are highly potent inhibitors of acetyl cholinesterase and other serine esterases. For example, phosphorothiolates (33 ; R = CH3; X = S) and (33; R = H ; X = S) are strong inhibitors of these enzymes while their oxygen analogues are not.75 Equilibrium constants for the phosphorylation of acetyl cholinesterase by (33) and (34) have been determined, and it appears that the relative efficiencies of the two classes of compounds (X = 0 or S) depend on the pKa of the leaving group (HXCH2CH2NR,).
0
II
(EtO),P -X-CH,CH,
I -0
kRMe,
72
G. Taborsky, Adu. Protein Chem., 1974, 28, 1. J. A. Todhunter and D. L. Purich, Biochem. Biophys. Res. Comm., 1974, 60,273. G. Hjelmquist, J. Andersson, B. Edlund, and L. Engstrom, Biochem. Biophys. Res. Comm.,
73
0. Schrecker, R. Stein, W. Hengstenberg, M. Gassner, and D. Stehlik, F.E.B.S. Letters, 1975,
70
71
1974, 61, 559. 51, 309. 74
75
S . Yamamoto and J. 0. Lampen, J. Biol. Chem., 1975,250, 3212. J. A. Maglothin and I. B. Wilson, Biochemistry, 1974, 13, 3520.
142
Organophosphorus Chemistry
Enzyme Mechanisms.-Methanolysis of the endo-isomer of uridine 2’,3’-cyclothiophosphate (34) by pancreatic ribonuclease gave R-uridine 3’-O-thiophosphate methyl ester (35; R = Me),7gand hence the methanolysis must take place by an in-line mechanism as has been suggested for the hydrolysis of (35).77 No pseudo-rotation is required for an in-line mechanism, in contrast to the case for an adjacent mechanism. Since (35) and uridine 2’,3’-cyclic phosphate have the same Km for their hydrolysis by pancreatic RNase and since the rate of enzymic hydrolysis of (35) is only oneeighth of that of its oxygen analogue, it has been concluded that the hydrolysis of the cyclic phosphate also takes place by an in-line mechanism (Scheme 4).76
n pseudorotation
0 OH
\
-0-p-
.OR
IIII
s
0 OH
\
RO-p-0‘
sl (35) Scheme 4
Rabbit-muscle phosphofructokinase phosphorylates only the B-anomer of fructofuranose, as shown by kinetic studies with D-fructose 6-phosphate (36; R1 = H; R* = OPO,H,) and D-tagatose 6-phosphate (36; R1 = OP03H2; R2 = Only the /3-anomer of methyl-cc/?-D-fructofuranoside6-phosphate, which was prepared by refluxing the disodium salt of D-fructofuranoside6-phosphate with an acid ion-exchanger in methanol, is phosphorylated by the enzyme; this confirms the results from the kinetic
76
77 78 79
W. Saenger, D. Suck, and F. Eckstein, European J. Biochem., 1974, 46, 559. D. A. Usher, D. I. Richardson, and F. Eckstein, Nature, 1970, 228, 663. R. Fishbein, P. A. Benkovic, K. J. Schray, I. J. Sewers, J. J. Steffens, and S. J. Benkovic, J. Biol. Chem., 1974,249, 6047. W. J. Ray,jun., J. Biol. Chem., 1969, 244, 3740.
143
Phosphates and Phosphonates of Biochemical Interest
Phosphoglucomutasecatalyses the interconversion of glucose 1- and 6-phosphates and requires the presence of bivalent metal ions for activity. While magnesium ions activate the enzyme most efficiently,it is active in the presence of manganese(@ions, and the latter can be used as a probe in magnetic resonance studies. By measuring the relaxation of the 31P n.m.r. signal of glucose 6-phosphate in the presence of manganese(@ ions, the relative positions of the metal and substrate have been determined.8o It has also been observed that whereas both anomers of glucose 6-phosphate bound to the enzyme, only the or-anomer underwent further reaction. The phosphoglucomutase reaction, proceeding via the 1,6-diphosphate, is another example of a reaction involving a phosphoenzyme, and the latter has been dephosphorylated recently by a variety of nucleophiles.81 The interaction of phosphoenol pyruvate (PEP) with a muscle pyruvate kinasegadolinium complex has been the subject of two recent investigations82s 83 which extend the earlier observation that whereas gadolinium(n) ions form complexes with this enzyme they are also potent inhibitor^.^^ lH N.m.r. spectroscopy indicated that a ternary PEP-GdII-enzyme complex might be formed 82 and this has been confirmed by 31P n . ~ . r Changes .~~ were observed in the longitudinal relaxation rate of the phosphorus atom of PEP in the presence of the kinase and gadolinium ions, showing that a complex was formed;83there was, however, no change in the water protonrelaxation rate.82 Alkaline phosphatase from E. coli has also been studied by magnetic r e s o n a n ~ e . ~ ~ Phosphonates are competitive inhibitors of alkaline phosphatase, and 19Fn.m.r. indicates that N-trifluoracetyl-l-aminoethylphosphonic acid (37) interacts strongly with the enzyme. No direct interaction between (37)and the metal ion responsible for enzymic activity could be detected, leading to the conclusion that there is a considerable distance between the metal ion and the substrate-binding site of alkaline phosphatase. There seems to be little difference in the mechanism of hydrolysis of phosphate and O-phosphorothioate monoesters by alkaline phosphatase although the rate of hydrolysis of the phosphorothioate can be much less than that for the CF,CONHCHP(O)(OH),
I
Me
(3 7)
H02C
Yp(o)(oH)2 C02H 0 (38)
phosphate.8e Hydrogen sulphide is not released from the phosphorothioate and hence a thiophosphoryl enzyme must be formed as an intermediate. In contrast, hydrogen sulphide and inorganic phosphate are the products of hydrolysis of inorganic thiophosphate by alkaline phosphatase. The hydrolysis of low concentrations of 4nitrophenyl phosphate by E. coli alkaline phosphatase is stimulated by 8O
81 82
D. G. Gadian, G. K. Radda, and R. E. Richards, Biochim. Biophys. Acta, 1974, 358, 57. P. P. Layne and V. A. Najjar, J. Biol. Chem., 1975,250,966. G . L. Cottam, K. M. Valentine, B. C. Thompson, and A. D. Sherry, Bi&hemistry, 1974, 13, 3532.
e3 G . L. Cottam and R. L. Ward, Biochem. Biophys. Res. Comm., 1975, 64, 797. ** K. M. Valentine and G . L. Cottam, Arch. Biochem. Biophys., 1973,158, 346. B5 H. Lilja, H. Csopak, B. Lindman, and G. Folsch, Biochim. Biophys. Acra, 1975, 384, 277. 86 J. F. Chlebowski and J. E. Coleman, J. Biol. Chem., 1974, 249, 7192.
Organophosphorus Chemistry
144
analogues of inorganic pyrophosphate such as methylene diphosphonate.8 7 This is taken to indicate that there are two active sites on the enzyme and that the hydrolytically stable analogues bind to one site and stimulate co-operatively88 the hydrolysis taking place at the other. An improved synthesis of (N-phosphonoacety1)-L-aspartate (38 ; X = NH), a transition-state analogue for aspartate transcarbamylase, has been reported.89The biosynthesis of pyrimidine nucleotides was inhibited in mammalian as well as bacterial 91 cells by (38 ;X = NH) and ~~-4,5-dicarboxy-2-ketopentylphosphonate (38; X = CH,) was also a potent inhibitor of aspartate transcarbamylase in mammalian The effectiveness of these phosphonates as inhibitors of nucleic acid biosynthesis makes them potential antitumour agents. Bis(4-nitrophenyl) methyl phosphate (39) reacted rapidly with the carboxyl esterases from liver and slowly with a-chymotrypsin.O2 Both 4-nitrophenyl residues were released and the phosphoenzyme formed contained one methyl phosphate residue for every active serine (Scheme 5). Hence (39) could be used as a spectro-
0
OMe
0 En-CH,O-P-OH
II
I OMe
+ HO
Scheme 5
photometric titrant for serine hydrolases. Serine residues in protamine have been phosphorylated chemically using orthophosphate and trichloroacetonitrile as condensing agent.93 The phosphate groups were released by treatment of the 87
88 89 90 91 92
g3
S. K. Kelly, J. W. Sperow, and L. G. Butler, Biochemistry, 1974, 13, 3503. R. T. Simpson and B. L. Vallee, Biochemistry, 1970, 9, 953. E. A. Swyrd, S. S. Seaver, and G. R. Stark, J. Biol. Chem., 1974, 249, 6945. T. Yoshida, G. R. Stark, and N. J. Hoogenraad, J. Biol. Chem., 1974, 249, 6951. K. D. Collins and G. R. Stark, J . Biol. Chem., 1971, 246, 6599. S. E. Hamilton, N. P. B. Dudman, J. De Jersey, J. K. Stoops, and B. Zerner, Biochirn. Biophys. Acta, 1975, 377, 282. B. Ullman and R. L. Perlman, Biochem. Biophys. Res. Comm., 1975, 63, 424.
Phosphates and Phosphonates of Biochemical Interest
145
phosphorylated protamine with a variety of phosphatases, 94 and this reaction sequence could be used to assay phosphatases. 8 Other Compounds of Biochemical Interest 3-Naphthyl di-, tri-, and tetra-phosphates have been synthesized from the monophosphate, DCC, and inorganic phosphate.95 The binding of these fluorescent polyphosphates to bovine oxyhaemoglobin was reversed by inorganic pyro- and tripolyphosphates and also organic phosphates, e.g. inositol hexaphosphate, enabling the binding constants of the non-fluorescent phosphates to be measured. Irradiation of an aqueous solution of phosphorothioate caused a marked change in its absorption spectrum and led to a product which contained a P : S ratio of 2 : 1.g6 The product did not contain a free SH group and may be a pyrothiophosphate. On irradiation of phosphorothioate in the presence of an acceptor, e.g. glucose, phosphoryl transfer to the acceptor took place with loss of sulphur. Cysteamine S-phosphate, on irradiation in aqueous solution, gave cysteamine, inorganic orthophosphate, and taurine, while aminoethanol 0-phosphate and inorganic phosphate were stable.
94 95 g6
H. Maeno and P. Greengard, Proc. Nat. Acad. Sci. U.S.A., 1969,64, 1349. T. Kuwajima and H. Asai, Biochemistry, 1975, 14, 492. H. Neumann and M. Sokolovsky, Biochim. Biophys. Acta, 1975, 381, 292.
8 Nucleotides and Nucleic Acids BY J. B. HOBBS
1 Introduction The past year has been an active one in nucleotide chemistry, with synthetic and methodological innovation in most areas. A new journal, that of Carbohydrates, Nucleosides, and Nucleotides, and the first two volumes of what promises to become a standard work of reference1 have been published. Affinity chromatography has become an indispensible weapon to the chemist and biochemist involved with the isolation and purification of biological macromolecules, and there is much evidence of this in the nucleotide field.2*3
2 Mononucleotides Chemical Synthesis.-Nucleoside phosphites are prepared in high yield by condensing nucleosides with phosphorous acid in the presence of tri-isopropylsulphonyl chloride (TPS). Silylation of these compounds, followed by oxidation with 2,2’dipyridyl disulphide, gives a versatile route for the preparation of phosphates or phosphate derivatives4 (Scheme 1). Treating intermediate (1) with a variety of nucleophiles leads to nucleotides containing correspondingly modified phosphate groups. If sulphur or diphenyl disulphide6are used in place of dipyridyl disulphide, the phosphorothioate (2) or phenyl thioester (3) are obtained in high yield on hydrolysis. 2-(NN-Dimethylamino)-4-nitrophenyl phosphate (4) may be used for specific 5’-phosphorylation of unprotected nucleosides. The reaction is acidcatalysed, presumably by protonation of the dimethylamino moiety. Moreover, if (4) is esterified with adenosine using DCC and the resulting diester heated with acetic acid in pyridine, cyclic 3’,5’-AMP (CAMP)is obtained in good yield. Di(2-t-butylphenyl) phosphorochloridate ( 5 ) is also a phosphorylating agent specific for the 5’-position of n~cleosides,~ selectivity being imposed by steric hindrance. Yields are fair, the advantage of the method being that the phosphate-protecting groups are acid- and base-resistant, allowing further derivatization. They are removed by 1 2
3
5
‘Basic Principles in Nucleic Acid Chemistry’, ed. P. 0. P. T’so, Academic Press, New York, 1974, Vols. 1 and 2. ‘Advances in Experimental Medicine and Biology’, ed. R. B. Dunlap, Plenum Press, New York, 1974, Vol. 42. ‘Methods in Enzymology’, ed. W. B. Jakoby and M. Wilchek, Academic Press, New York, 1974, Vol. 34. T. Hata and M. Sekine, Tetrahedron Letters, 1974, 3943. T. Hata and M. Sekine, J. Amer. Chem. SOC.,1974, 96, 7363. Y.Taguchi and Y . Mushika, Tetrahedron Letters, 1975, 1913. J. Hes and M. P. Mertes, J . Org. Chem., 1974, 39, 3767.
146
147
Nucleotides and Nucleic Acids
Hi)
Me,SiO
PYS'
0
II
~
Me,SiO
Me,SiO
-Me,SiSpy
(Me, S i 0 ) g -0
PYS
Me,SiO
(1) T = Thymine; py = 2-pyridyl Reagents:i, Me,SiCl; ii, py-S-S-py Scheme 1
hydrogenolysis. Di(2-nitrobenzyl) phosphorochloridate (6) has been used to phosphorylate protected nucleosides.s The protecting groups are removed photolytically ( A > 305 nm) and carbonyl-containing by-products of photolysis can be removed using a polymer-linked semicarbazide. In the presence of cupric acetylacetonate, 8-quinolyl phosphate (7) or its alkyl esters (8) react with protected nucleosides to form nucleoside monophosphates or the corresponding mixed diesters. Thiophosphate reacts with acrylonitrileto form S-(2-cyanoethyl)thiophosphate, a species 0
ll I 0
HO-P-OH
I
&Me,
(4)
* @
(5)
M. Rubinstein, B. Amit, and A. Patchornik, Tetrahedron Letters, 1975, 1445. H. Takaku and Y. Shimada, Chem. and Pharrn. Bull. (Japan), 1974,22, 1743.
148
Organophosphorus Chemistry 0 QO+
0
O=P-OH
I
OR (7) R = H (8) R = Alkyl which phosphorylates thymidine in DMF at 70 “C. Since thiophosphate could be formed by combustion of its constituent elements and acrylonitrile is a plausible constituent of the ‘primaeval soup’, such a reaction could have relevance for prebiotic phosphorylation.l0 Guanosine is notoriously difficult to phosphorylate in good yield, and normal phosphorylating methods fail with 5’-amino-5’-deoxyguanosine.However, phosphorylation at the 5’-position is achieved in high yield using a diester phosphorochloridate and NN-di-isopropylethylamine (Hunig base) in triethyl phosphate.ll Phosphorus oxychloride in triethyl phosphate continues to be the system most frequently applied for 5’-phosphorylation of unprotected nucleosides 12-14 and has also been used to phosphorylate unprotected dinucleoside(3’-5’) monophosphates at the free 5’-hydroxy-group, in moderate yield.15 However, the observation that trialkyl phosphates will alkylate purines on heatingls prompts a word of caution against using heat to dissolve nucleosides of low solubility in this reagent. Preparative enzymic synthesis of nucleoside 5’-phosphates has been described, using wheat shoot phosphotransferase with 4-nitrophenyl phosphate as d0nor.l’ The enzyme shows specificity for a primary hydroxy-group, and will phosphorylate analogues containing modified sugars, and even 1-(2-hydroxyethyl)cytosine and 5-(2-hydroxyethy1)uracil. The quantitative recovery of product and unreacted nucleoside commends this technique if only small quantities of material are available. Some useful base-modifications carried out directly on nucleotides have been described, including the reaction of adenine nucleotides with hydrogen selenide to give 6-seleno-deri~atives,~~ and the direct fluorination of UMP to give the 5-fluorouridine derivative.19The reaction of CMP or AMP with cyanoacetylene gives the highly fluorescent (9) or Solvolysis of cytidine nucleotides in hydrogen M. R. Slabaugh, A. J. Harvey, and J. Nagyvary, J. Mol. Euol., 1974, 3, 317. K. Schattka and B. Jastorff, Chem. Ber., 1974, 107, 3043. T. M. K. Chiu and R. B. Dunlap, J. Medicin. Chem., 1974, 17, 1029. C. H. Hong, G. L. Tritsch, A. Mittelman, P. Hebborn, and G. B. Chheda, J. Medicin. Chem., 1975, 18,465. l4 P. D. Cook, R. J. Rousseau, A. M. Mian, R. B. Meyer, jun., P. Dea, G. Ivanovics, D. G. Streeter,J. T. Witkowski, M. G. Stout, L. N. Simon, R. W. Sidwell, and R. K. Robins, J. Amer. Chem. SOC.,1975,97,2916. 1 5 A. Holq, J. Carbohydrates Nucleosides Nucleotides, 1975, 2, 63. l6 K. Yamauchi, M. Hayashi, and M. Kinoshita, J. Org. Chem., 1975, 40, 385. l7 J. Giziewicz and D. Shugar, Acta biochim. polon., 1975, 22, 87. 18 C.-Y. Shiue and S.-H. Chu, J.C.S. Chem. Comm., 1975, 319. l9 M. J. Robins, G. Ramani, and M. MacCoss, Canad. J. Chem., 1975, 53, 1302. 20 Y. Furukawa, 0. Miyashita, and M. Honjo, Chem. and Pharm. Bull. (Japan), 1974, 22, 2552.
lo 11 l2 13
149
Nucleotides and Nucleic Acidr
sulphide yields the corresponding 4-thiouridine compounds,21a reaction also applicable to polyribocytidylic acid [p01y(rC)].~~ 3-Deazaguanylic acid has been prepared by ring-closure of an imidazole nu~1eotide.l~
0
HO-P-
II I -0 Hi) OH
Ho%u 0
0
~-
H, HO-P=O
I
CHZW (11) U = Uracil
Uridine 2’- and 3’-aminomethanephosphonates (11) have been prepared via condensation of 5 ’-0tr ityluridine with N-benzy loxycarbonylaminomethanephosphonic acid, using TPS.23On incubation with pancreatic RNase A, no phosphonate cleavage is observed, but uracil is lost ! It is thought that (11) may bind to the enzyme in such a conformation as to facilitate attack of the wino-group at the C-1’-position. Another curious reaction is the hydrolysis by bovine pancreatic DNase of 4-nitrophenol from the 3’-group of deoxythymidine 3’,5’-di-4-nitrophenyl phosphate.24On cleaving DNA, this enzyme yields 5’-phosphomonoesters. Cyclic Nucle0tides.-A high-yield preparation of nucleoside 3’,5’-cyclic phosphates via phosphotriester intermediates25 (Scheme 2) possesses the advantage that all intermediates are isolable as pure crystalline solids. Adenosine 3’,5’-cyclic phosphorothioate has been prepared by treating adenosine 2’,3’-diacetate with di(4nitrophenyl) thiophosphoryl chloride, deacetylating the product, and cyclizing with potassium t-butoxide.26 The synthesis described previously was erroneous.27The analogue binds tightly to CAMP-dependentprotein kinase. If an Escherichia coli mutant that is 21
T. Ueda, K. Miura, M. Imazawa, and K. Odajima, Chem. and Pharm. Bull. (Japan), 1974,22, 2377.
28
23 24 25
A. A. Hochberg and M. Keren-Zur, Nucleic Acid Res., 1974, 1, 1619. A. Holg and N. N. Gulyaev, J. Carbohydrates Nucleosides Nucleotides, 1974, 1, 85. T.-H. Liao, J . Biol. Chem., 1975, 250, 3721. J. H. van Boom, P. M. J. Burgers, P. van Deursen, and C. B. Reese, J.C.S. Chem. Comm., 1974, 618.
26
27
F. Eckstein, L. P. Simonson, and H. P. Bar, Biochemistry, 1974, 13, 3806. F. Eckstein, J. Amer. Chem. Soc., 1970, 92, 4718.
6
150
Organophosphorus Chemistry + 3',5'-cUMP
HO OR2
0 OR2
I
PhO-P-0
I
OPh
U = Uracil
Reagents: i, (PhO),POCI in acetonitrile; ii,
(1
; iii, NH,; iv, But0 K+ in DMSO; v, H+
N C1 Me
Scheme 2
deficient in cAMP receptor protein is supplied with H332p0q during log-phase growth, it excretes [32P]~AMP.28 This can be used preparatively, a specific activity of ca. 4 Ci mmol-l being attainable. Many new derivatives of cAMP have been described, involving substitution at the 2-29and 8-p0sitions,~~ and on N-6.13Two new fluorescent analogues have been described, 2-aminopurineriboside 3',5'-cyclic phosphate 31 (12) and 1,N6-etheno-2-aza-adenosine-3',5'-cyclicphosphate32(13). Cleavage of the phosphate ring in (12) produces changes in the fluorescence and absorption spectra that are large enough to use for kinetic measurements. Spin-labelled cAMP derivatives have also been prepared.33Circular dichroism (c.d.) and e.s.r. studies allow correlation of conformation and spin-label mobility and their changes on enzyme binding. New 8-acyl and 8-alkyl derivatives of cGMP have been described, using free radicals of the appropriate groups to effect s ~ b s t i t u t i o n 8-Seleno-derivatives .~~ of cGMP have also been ~ynthesized.~~ Some alkyl phosphotriesters of cAMP and cUMP have been described, the former being prepared from cAMP using an arenesulphonyl chloride and alcohol,36the latter by direct alkylation of cUMP with dia~oalkanes.~' The cAMP esters are dealkylated by thiourea under mild conditions to give CAMP,suggesting that mercapto-groups in living tissue might perform this function to render these compounds therapeutically 28 29
H. Yamazaki, K. Potter, and G. Chaloner-Larsson, Analyt. Biochem., 1974, 62, 546. R. B. Meyer, jun., D. A. Shuman, and R. K. Robins, J. Amer. Chem. SOC.,1974, 96, 4962; M. Fikus, J. Kwast-Welfeld, Z. Kazimierczuk, and D. Shugar, Acta. biochim. polon., 1974, 21, 465.
31
32 33 34
K. Muneyama, D. A. Shuman, K. H. Boswell, R. K. Robins, L. N. Simon, and J. P. Miller, J. Carbohydrates Nucleosides Nucleotides, 1974, 1, 55. K. H. Scheit, J. Carbohydrates Nucleosides Nucleotides, 1974, 1, 385. K. C. Tsou, K. F. Yip, and K. W. Lo, Analyt. Biochem., 1974, 60, 163. J. Hoppe and K. G. Wagner, European J. Biochem., 1974, 48, 519. L. F. Christensen, R. B. Meyer, jun., J. P. Miller, L. N. Simon, and R. K. Robins, Biochemistry, 1975, 14, 1490.
35 36
37
S.-H. Chu, C.-Y. Shiue, and M.-Y. Chu, J. Medicin. Chern., 1975, 18, 559. R. N. Gohil, R. G. Gillen, and J. Nagyvary, Nucleic Acid Res., 1974, 1, 1691. J. Engels and W. Pfleiderer, Tetrahedron Letters, 1975, 1661.
Nucleotides and Nucleic Acids
151
OH (12)
I
OH
/i\
0 c1 (15) B = Adenine, cytosine, uracil, or guanine
(14)
R20
‘
(16) X = S; R’ = R2 = R3 = H (17) X = 0;R’ = PO,&; R’ = R3 = MeCO (18) X = 0;R’ = Rz = R3 = H
active; the ethyl ester is a powerful anti-tumour agent, and its X-ray structure has been reported.3sThe diastereoisomers of the benzyl ester of cUMP are separable, the axial : equatorial ratio of 70 : 30 for the position of the benzyl group3’ being consistent with thermodynamic preference for the axial substituent in 1,3,2-dioxaphosphorinan-Zones. If N-benzoyl 8,3’-S-cycloadenosine-5’-phosphateis treated with DCC and then debenzoylated, the seven-membered 2’,5’-cyclic phosphate (14) is Treatment of (14) with Raney nickel gives cordycepin (3’-deoxyadenosine) 2’,5’-cyclic phosphate. Compound (14) is stable to acid, base, and snake-venom phosphodiesterase, whereas the cordycepin derivative is split by acid to give adenine s* F. A. Cotton, R. G. Gillen, R. N. Gohil, E. E. Hazen, jun., C. R. Kirchner, J. Nagyvary, J. P. Rouse, A. G. Stanislowski, J. D. Stevens, and P. W. Tucker, Proc. Nat. Acad. Sci. U.S.A., 1975,72, 1335. 39
M. Ikehara and J. Yano, Nucleic Acid Res., 1974, 1, 1783.
152
0rganophosphor us Chemistry
and sugar phosphates. Both 2’- and 3’-UMP are cyclized by diethyl pyrocarbonate in aqueous solution to give ~’,~’-cUMP,~O a reaction which may be of use for derivatization of the 3’-terminal of polynucleotides. Y-UMP is not cyclized by this reagent. Ribonucleosides are converted into their 2’,3’-cyclic phosphate-5’-phosphates in a single step by solution in pyrophosphoryl chloride at low temperature followed by neutral buffered hydrolysis of the presumed intermediate (1 5).41 If 8-mercaptoadenosine-2’,3’-cyclic phosphate is treated with trimethylsilyl chloride, only the 3’phosphate of 8,2’-S-cycloadenosine (16) is Condensation of the 5’monomethoxytrityl derivative of (1 8) with (1 7) using DCC gives, after deblocking, the dinucleoside monophosphate of (1 8),43 which is completely resistant to spleen and snake-venom phosphodiesterase, and which, from c.d. measurements, appears to stack along a left-hand screw axis. The synthesis of an ApUpG analogue containing (18) as the 5’-terminus has been described,44and this and similar analogues have been tested for their ability to bind the appropriate amino-acyl-tRNA to ribosomes.45 Only analogues containing nucleotides of anti-conformation which were capable of Watson-Crick base-pairing to the anticodon trinucleotide could effect binding to the ribosome. Affinity Chromatography.-If an N-protected o-amino-alkyl phosphate is coupled to a nucleoside 5’-monophosphate using carbonyldi-imidazoleand then deprotected, the primary aliphatic amino-group of the resulting unsymmetrical pyrophosphate may be bound to Sepharose that has been treated with cyanogen bromide (CNBrSepharose), to give an immobilized nucleotide bound via its phosphate group (19). This method has been used to immobilize AMP,46$47 UMP,47GMP,48and tRNA4* (which concomitantly lost its acceptor activity). More frequent use has been made of purine nucleotides immobilized via a diamino-alkane spacer at C-6463 55-59 or C-846,47*49-53 (a sulphur link has also been Linkage via the sugar residue following periodate oxidation of a ribonucleotide (20) may be achieved by employing 479
40
4l 42 43
44 45 46
47
48 49 50
5l 52
53
54 55 56
57 58
59
51p539
F. Solymosy, L. Ehrenberg, and I. Fedorcsak, Nucleic Acid Res., 1975, 2, 985. A. Simoncsits and J. Tomasz, Biochim. Biophys. Acta, 1975, 395, 74. M. Ikehara and T. Tezuka, J. Carbohydrates Nucleosides Nucleotides, 1974, 1, 67. M. Ikehara, S. Uesugi, and J. Yano, J. Amer. Chem. SOC.,1974, 96, 4966. M. Ikehara, T. Nagura, and E. Ohtsuka, Chem. and Pharm. Bull. (Jupan), 1974, 22, 2578. E. Ohtsuka, T. Nagura, K. Shimokawa, S. Nishikawa, and M. Ikehara, Biochim. Biophys. Acta, 1975, 383, 236. I. P. Trayer, H. R. Trayer, D. A. P. Small, and R. C. Bottomley, Biochem. J., 1974,139, 609. I. P. Trayer and H. R. Trayer, Biochem. J., 1974, 141, 775. J. Smrt, Coll. Czech. Chem. Comm., 1975, 40, 1053. C.-Y. Lee, D. A. Lappi, B. Wermuth, J. Everse, and N. 0. Kaplan, Arch. Biochem. Biophys., 1974, 163, 561. C.-Y. Lee and N. 0. Kaplan, Arch. Biochem. Biophys., 1975,168, 665. H. R . Trayer and I. P. Trayer, F.E.B.S. Letters, 1975, 54, 291. J. Ramseyer, H. R. Kaslow, and E. N . Gill, Biochem. Biophys. Res. Comm., 1974, 59, 813. B. Jergil, H. Guilford, and K. Mosbach, Biochem. J., 1974, 139,441. E. S. Severin, S. N. Kochetkov, M. V. Nesterova, and N. N. Gulyaev, F.E.B.S. Letters, 1974, 49, 61. M. J. Comer, D. B. Craven, M. J. Harvey, A. Atkinson, and P. D. G . Dean, European J. Biochem., 1975, 55, 201. C. R. Lowe and K. Mosbach, European J. Biochem., 1975, 52, 99. P. Brodelius, P.-0. Larsson, and K . Mosbach, European J. Biochem., 1974, 47, 81. W. L. Dills, jun., J. A. Beavo, P. J. Bechtel, and E. G. Krebs, Biochem. Biophys. Res. Comm., 1975, 62, 70. M. Lindberg and K. Mosbach, European J. Biochem., 1975, 53,481.
Nucleotides and Nucleic Acids
153 0
0
-0
-0
Sepharose-HN(CH,),
HO OH (19) B = Adenine, uracil, or guanine
HO
I
OH NHCOR (20) n = 0, 1, or 3; A = Adenine
CNBr-Sepharose hydrazide~.~~ Immobilized nucleotides have been used for , ~55~ , myosin,46* 51s 61 and the purifying dehydrogenase~,~~t 55-57 k i n a ~ e s 50$ CAMP-binding regulatory subunit of protein k i n a ~ e . ~6 8~ - ~ ~ , A critical comparison of methods for coupling nucleotides and polynucleotides to solid supports has appeared.62 Equilibrium dialysis methods have been used to compare the binding isotherm of ApA with poly(rU) attached to CNBr-Sepharose at If the poly(rU)-Sepharose has pH 6 with that of ApA to poly(rU) free in s01ufion.~~ first been washed at pH 10, the isotherms are identical; if not, they are markedly different. It is thought that multipoint attachment through the 5’-phosphate and the 3’+5’-phosphodiester linkages takes place initially, and that washing at pH 10 hydrolyses the triester links. Optimum conditions for coupling DNA to CNBrSepharose have been defined, and employed to purify DNA polymerase I and RNA polymerase from E. C O Z ~ . SV-40 ~~ DNA fragments have been bound to neutral cellulose using a water-soluble carbodi-imide, and SV-40 complementary RNA to phosphocellulose using carbonyldi-imida~ole.~~ Columns of these materials were used to isolate complementary sequences by hybridization. 9
49s
503
3 Nucleoside Polyphosphates Chemical Synthesis.-Treatment of nucleoside 5’-phosphates with di-n-butylphosphinothioyl bromide in pyridine gives the corresponding mixed anhydride (21) (Scheme 3), which is stable in the presence of water but which gives the nucleoside 5’-di- and -tri-phosphates in high yield on treatment with orthophosphate or pyrophosphate and silver ion.66If ATP is treated with DCC in dry pyridine, the 31Pn.m.r. 60
61
62 63 64
65
66
F. Hansske, M. Sprinzl, and F. Cramer, Bio-organic Chem., 1974, 3, 367. R. Lamed and A. Oplatka, Biochemistry, 1974, 13, 3137. P. V. Sundaram, Nucleic Acid Res., 1974, 1, 1587. S. Okada, Y. Husimi, S. Tanabe, and A. Wada, Biopolymers, 1975, 14, 33. D. J. Armdt-Jovin, T. M. Jovin, W. Bahr, A. M. Frischauf, and M. Marquardt, European J. Biochem., 1975,54, 411. T. Y. Shih and M. A. Martin, Biochemistry, 1974, 13, 3411. T . Hata, K . Furusawa, and M. Sekine, J.C.S. Chem. Comm., 1975, 196.
Organophosphorus Chemistry
154
B = Adenine, cytosine, uracil, guanine, or thymine; R = H or OH Scheme 3
spectrum indicates the formation of monoadenosine trimetaphosphate (22) by phosphate side-chain cycli~ation.~~ All three phosphorus resonances lie close to that of the p-phosphorus atom in ATP, generating an ABC pattern. The reaction of (22) with water rapidly regenerates ATP. A series of 5’-C-acylaminomethyl derivatives of AMP and ATP has been synthesized with a view to correlating substrate properties for enzymes with steric requirements at the S’-po~ition.~* The nucleosides are elaborated via condensation of nitromethane and adenosine4’-aldehyde, and phosphorylated by standard methods. ATP-y-anilidate (23), prepared by condensing
HO OH
0
0
0
-0
-0
-0 HO OH
aniline and ATP using carbodi-imide, is reported to be a substrate for DNAdependent RNA polymerase from E. coli, and also to act as a chain initiator.69The interaction of enzymes with nucleoside phosphorothioates has been reviewed. 70 Adenosine 5’-0-(3-thiotriphosphate) has been used to investigate ATP binding to myosin,71and as a result the two-step processes of ATP association and ADP dissociation have been proposed. The nucleoside 5’-S-thiotriphosphates (24) and (25) are not substrates for RNA polymerase from E. ~ o l iand , ~ are ~ only weak inhibitors, while (26) is neither substrate nor inhibitor for DNA polymerase I.73lH N.m.r. spectra suggest that these analogues do not possess the gauche,gauche conformation (27) which usually occurs in nucleotides, owing to the greater length of the C-S bond, and it is postulated that this conformation is a prerequisite for substrates of these enzymes. The finding that adenosine 5’-methylenediphosphonate (28) is photophosphorylated in spinach chloroplasts has led to the proposal 74 that there are two 67
e8 69 70
71 72
73 74
T. Glonek, R. A. Kleps, and T. C. Myers, Science, 1974, 185, 352. F. Kappler and A. Hampton, J. Org. Chem., 1975, 40, 1378. M, A. Grachev and E. F. Zaychikov, F.E.B.S. Letters, 1974, 49, 163. F. Eckstein, Angew. Chem., 1975, 87, 179. C. R. Bagshaw, J. F. Eccleston, F. Eckstein, R. S. Goody, H. Gutfreund, and D. R. Trentham, Biochem. J., 1974, 141, 351. A. Stutz and K. H. Scheit, European J . Biochem., 1975, 50, 343. K. H. Scheit and A. Stiitz, J . Carbohydrates Nucleosides Nucleorides, 1974, 1, 485. A. Horak and S. Zalik, Nature, 1974, 249, 858.
155
Nucleotides and Nucleic Acids 0
0
0
H II P-s -10 -1 -0
II -0-P-o-P-o
I
-0
BB HO R
HO OH
(28) A = Adenine
(24) R = OH, B = adenine (25) R = OH, B = uracil (26) R = H, B = thymine
ction from C-5‘ to C-4’ of (24)-(26) in conformation The first term describes the orientation of d with respect of 2 with respect to c’.
(27)
separate ADP pools present, one tightly bound and undergoing a myokinase-type reaction with electron-driven regeneration of AMP to ADP, and the other loosely bound, being the acceptor species in a transphosphorylation reaction. Diguanosine-(5’-5’)-tetraphosphate is the major purine nucleotide in brineshrimp platelets, and when these are incubated with 32P-labelledpyrophosphate, [p,y-32P]GTPis formed,7sa convenient method for preparation of this compound at activities up to 15 mCi mmol-l. Guanosine 5’-diphosphate-3’-diphosphate(29) has been prepared by treating (30) with carbonyldi-imidazole and orthophosphate, and deblocking with weak acid.76Together with the 5’-triphosphate (31), this compound
H[-I)-O%G
-0
n
9 -
OR’
1 O P = O 1
I
OR‘ G = Guanine
(29) (30) (31) (32) (33) (34) (35) (36)
0
I
-0
n n n n n n n n
= 2; = 1;
= 3; = 2;
= 1; = 3;
= 3; = 3;
R’ = R’ = R’ = R’ = R’ = R’ = R’ = R’ =
P0,H-; R2 = H H; R2 = CH(Me)(OMe) P0,H-; R2 = H PO,SH-; R2 = H
Rz = H adenosine-5’; R2 = H uridine-5’; R2 = H cytidined‘; R2 = H
0
-0
-0 HO OH
(37) X = CH, (38) X = NH 75 ‘6
A. H. Warner, Biochim. Biuphys. Acta, 1975, 383, 229. J. W. Kozarich, A. C. Chinault, and S. M. Hecht, Biochemistry, 1975, 14, 981.
156
Organophosphorus Chemistry
is produced in vitro in a ribosomal system from E. coZi in which protein synthesis is idling, via phosphorylation of GDP or GTP by ATP.77This reaction is rever~ible.~~ Intact ribosomes, mRNA, uncharged tRNA, and E. coZi ‘Stringent Factor’ are required, though tRNA can be replaced by the fragment T p Y ~ c p G p Adenosine .~~ 5’-0-(3-thiotriphosphate) can replace ATP, leading to formation of (32).80Treatment of (33) or its 2’,5’-isomer with diphenyl phosphorochloridate and pyrophosphate gives guanosine 2’,3’-cyclic phosphate-5’-triphosphate, which is a substrate for RNase T,, forming (34), (35), and (36) in the presence of the appropriate nucleosides. These compounds have been studied for their ability to interact with elongation factor 1 (EF 1) from wheat embryos, and to replace GTP in the ternary complex EF 1 - amino-acyl-tRNA-GTP and in the GTP-dependent EF 1-catalysed binding of amino-acyl-tRNA to ribosome in protein synthesis.81,82 Guanylylmethylenediphosphonate (37) forms a complex with phenylalanyl-tRNA and EF Tu (from E. coZi) which is stable enough to permit gel filtrationa3and crystalli~ation.~~ GTP and its analogues, particularly (38), have been studied with regard to their activating effect on adenyl cyclase from various sources. They act synergistically with horm o n e ~ , but ~ ~(38) - ~ still ~ activates the enzyme when the hormone receptor is blocked or absent.88The analogues stimulate the enzyme more strongly than GTP,a6s88-90 competing with it at the same single class of regulatory 8 6 ~ 8 9 - 9 1 Binding of the analogues is strong almost to the point of irre~ersibility,~~’ a 6 - 92 a fact which has been used to separate the binding protein by affinity chromatography.86 Affinity Labelling.-The photolabile 8-azido-ATP (39) is a substrate for the cationstimulated ATPases of human erythrocyte membranes in the absence of U.V. light. On irradiation, irreversible inactivation of the ATPases occurs, and three protein components of the membrane are labelled.93The presence of ATP protects the enzymes against inactivation. Compounds (40), (41), and (42) all bind to (Na+ K+)-ATPase, (40) and (41) being substrates for this enzyme and (42) giving ATP-protected inactivation.94 Addition of dithiothreitol halts inactivation but does not restore enzymic activity. It is thought that a thioether link is formed in the active site of the enzyme. DNA-dependent RNA polymerase from E. coZi binds 5-formyluridine-5’-triphosphate, in competition with ATP. The analogue is thought to form a Schiff base with the enzyme, and reduction with borohydride leads to covalent
+
77 78 79
82
83 84
85 86
87 88
89
91 92
93 94
L. Beres and J. Lucas-Lenard, Biochim. Biophys. Acta, 1975, 395, 80. J. Sy, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 3470. D. Richter, V. A. Erdmann, and M. Sprinzl, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 3226. J. Sy, Biochemistry, 1975, 14, 970. A. Simoncsits, J. Tomasz, and J. E. Allende, Nucleic Acid Res, 1975, 2, 257. J. E. Allende, C. C. Allende, A. Simoncsits, and J. Tomasz, J. Biol. Chem., 1975, 250, 2056. J. C. Lee and M. C. Roach, Biochem. Biophys. Res. Comm., 1975, 63, 864. K. Arai, M. Kawakita, and Y. Kaziro, J . Biochem. (Japan), 1974, 76, 283. P. Cuatrecasas, S. Jacobs, and V. Bennett, Proc. Nut. Acad. Sci. U.S.A., 1975, 72, 1739. T. Pfeuffer and E. J. M. Helmreich, J. Biol. Chem., 1975, 250, 867. T. Hanoune, M.-L. Lacombe, and F. Pecker, J . Biol. Chem., 1975, 250,4569. C. London, Y. Salomon, M. C. Lin, J. P. Harwood, M. Schramm, J. Wolff, and M. Rodbell, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 3087. R. J. Lefkowitz, J. Biol. Chem., 1974, 249, 6119. R. J. Lefkowitz, J. Biol. Chem., 1975, 250, 1006. A. M. Spiegel and G . D. Aurbach, J. Biol. Chem., 1974, 249,7630. R. J. Lefkowitz and M. G . Caron, J. Biol. Chem., 1975, 250,4418. B. E. Haley and J. F. Hoffmann, Proc. Nat. Acad. Sci. U.S.A., 1974,71, 3367. R. Patzelt, H. Pauls, and W. Schoner, Z . physiol. Chem., 1974, 355, 1237.
Nucleotides and Nucleic Acids
157 (39) R' = N,; R2 = NH,
0
II I -0
-0-P-N-P-0-P-0
0
II I -0
0 (40) R' = H; R2 = C1
(41) R' = H; R2 = SH (42) R' = H; R2 = S
G N O,N -
0 0 N 3 00 - Y - O - - - O q G
II
II
-0
HO OH (44) G = Guanine
labelling on both /3- and ~ - s u b ~ n i tBinding s . ~ ~ to the former was diminished by the initiation inhibitor rifampicin, suggesting that the analogue binds at or near a site that binds rifampicin. 6,6'-Dithiobis-(inosinylimidodiphosphate) (43) inactivates the ATPase of myosinand itsproteolysisfragmentsby formingmixed disulphides with cysteine residues.9sThese can be split by [14C]cyanideion, the thiocyanates formed allowing determination of the stoicheiometry of binding and identification of the subunits labelled. The photoaffinity label (44)has been used to identify the proteins of 70s ribosomes involved in the GTP binding site.07Ribosomal proteins 9s-100 and RNA lol have also been affinity-labelled using bromoacetylated derivatives of puromycin,lol tRNA,9Sand the initiation codon ApUpG.@O* loo Metal Complexes.-A complex of lanthanum and ATP inhibits yeast phosphoglycerate kinase, competing with the natural substrate [Mg,ATPI2-.lo2Similar results are obtained with other lanthanide complexes of ATP. N.m.r. spectroscopic titration V. W.Armstrong, H. Sternbach, and F. Eckstein, F.E.B.S. Letters, 1974, 44, 157. P. D. Wagner and R. G. Yount, Biochemistry, 1975, 14, 1900, 1908. Q7 J. A. Maassen and W. Moller, Biochem. Biophys. Res. Comm., 1975, 64, 1175. 98 M. Sopori, M. Pellegrini, P. Lengyel, and C. R. Cantor, Biochemistry, 1974, 13, 5432. Q9 E. Lanka and 0. Pongs, 2.physiol. Chem., 1974,355, 1222. l o o 0. Pongs and E. Lanka, Proc. Nut. Acud. Sci. U.S.A., 1975, 72, 1505. 101 P. Greenwell, R. J. Harris, and R. H. Symons, European J. Biochem., 1974,49, 539. l o 2 P. Tanswell, E. W. Westhead, and R. J. P. Williams, F.E.B.S. Letters, 1974, 48, 60. 95 g6
4
158
Organophosphorus Chemistry
reveals a single metal - nucleotide binding site at pH 6.3, and gel filtration indicates two sites at pH 7.8. Chromium(r1x)-ATP shows competitive kinetics with respect to [MgII,ATPI2-, but non-competitive with regard to glucose, on initial binding to yeast hexokinase,lo3thus indicating random addition of substrates. On longer incubation a sugar-mediated tight binding takes place, probably with concomitant conformational change. [CrIII,ATP]- is a slow substrate for the enzyme. Since [CrIII,8-bromo-ATP]also shows tight binding and inhibition, the nucleotide in [CrIII,ATP]- may be in the syn-conformation on the enzyme. A number of new chromium-nucleotide complexes have been prepared.lo3 4 Oligo- and Poly-nucleotides Chemical Synthesis.-When increasing quantities of TPS are added to 3’-O-acetylTMP in pyridine, the proton-decoupled 31P n.m.r. spectrum shows first a signal corresponding to the symmetrical pyrophosphate, then the linear tripolyphosphate, and then a singlet ascribed to the monomeric metaphosphate (45).lo4Similar treatment of a mixture of 3’-O-acetyl-TMP with 4-nitrophenyl phosphate generates the same signal, without evidence of splitting, suggesting that only one phosphorus atom is involved, and the proton-coupled spectrum shows methylene splitting consistent with structure (45). The chemical shift lies close to that observed for an unidentified product obtained during generation of methyl rnetaphosphate by a pyrolytic method lo5 (possibly the metaphosphate itself?). It thus seems likely that condensations involving TPS may be mediated via the monomeric metaphosphate. A phosphite coupling procedure has been described for generating internucleotidic links. Treatment of a solution of 5’-phenoxyacetylthymidinewith 2-chlorophenyl phosphorodichloridite (46) at low temperature in the presence of base, followed by addition of 3’-O-monomethoxytritylthymidineand oxidation with iodine, gives the phosphotriester (47), which on deblocking gives TpT in fair yield.loBThe internucleotidic link has also been introduced via nucleoside silylphosphites as in Scheme 1; the 5’-blocked nucleoside 3’-phosphate thiophenyl ester analogous to (3) is formed and used for coupling with the 5’-hydroxy-group of a second nuc1eo~ide.l~~ The thiophenyl group is removed by brief treatment with weak alkali. Some internucleotide cleavage has been observed on hydrolysis of phenyl groups used to block phosphate in the ‘triester’ oligonucleotide synthesis, and new conditions for deblocking have been described.lo8 Deoxyribo-oligonucleotideshave been prepared using 5’-protected deoxynucleoside 3’-phosphorodianilidate units [e.g. (48)], which Phosphate deblocking is effected are prepared using dianilidophosphorochloridate.los by amyl nitrite. Treatment of deoxynucleoside 5’-monophosphates with excess formyl acetate in pyridine gives the corresponding 3’-formate esters (49) quantitatively. lo3K. lo4 D.
D. Danenberg and W. W. Cleland, Biochemistry, 1975, 14, 28. G. Knorre, A. V. Lebedev, A. S. Levina, A. I. Rezvukhin, and V. F. Zarytova, Tetrahedron, 1974, 30, 3073. lo5C. H. Clapp and F. H. Westheimer, J. Amer. Chem. SOC.,1974, 96, 6710. lo6R. L. Letsinger, J. L. Finnan, G . A. Heavner, and W. B. Lunsford, J . Amer. Chem. SOC.,1975, 97, 3278. lo’ M. Sekine and T. Hata, Tetrahedron Letters, 1975, 171 1. lo8 J. H. van Boom, P. M. J. Burgers, P. H. van Deursen, R. Arentzen and C. B. Reese, Tetrahedron Letters, 1974, 3785. lo9 W. S . Zielinski and J. Smrt, Coll. Czech. Chem. Comm.,1974, 39, 2483.
Nucleotides and Nucleic Acids
159
""-QT
0
R'O
MeCO), (45) T = Thymine
I
(47) R' =' phenoxyacetyl; R' = monomethoxytrityl
0
I
O=P(NHPh), (48) T = Thymine
H103p0D HCO6 (49) B = Base
0
""3Yu (50) PEG = poly(ethy1ene glycol)
(51) U =. Uracil
I
0--p-0-
OH (52) T = Thymine
These may then be used for the synthesis of oligodeoxynucleotides.The 3'-hydroxygroup is deblocked by the triethylammonium carbonate buffer used to destroy excess condensing agent at each stage, reducing chain elongation to a single step.110The method could readily be applied to synthesis on a support such as the 2-hydroxyethyl phenyl thioether of a poly(ethy1ene glycol) derivative (50), a soluble polymer which is condensed with a deoxynucleoside5'-phosphate to form a template for synthesis of the chain.lll Final removal is effected by N-chlorosuccinimide and base. Solidsupport synthesis of oligothymidylates has been described using thymidine attached to a copolymer of styrene and 4-vinylbenzoic acid by esterification at the 3'-hydroxygroup as template.l125'4-Protected thymidine 3'-phosphorochloridate phenyl ester is used for each addition, in the presence of 1-methylimidazole.The oligothymidylate chain thus prepared has each internucleotide link protected by a phenyl group. De110
H. Seliger, H. Schiitz, E. Saur, and M. Philipp, J. Carbohydrates Nucleosides Nucleotides, 1975, 2, 79.
111
l12
F. Brandstetter, H. Schott, and E. Bayer, Tetrahedron Letters, 1974, 2705. R. C. Pless and R. L. Letsinger, Nucleic Acid Res., 1975, 2, 773.
160
Organophosphorus Chemistry
blocking follows standard methods. If 2’,3’-U-(dibutylstanny1ene)uridine (51) is treated with 2-nitrobenzyl bromide in DMF, only 2’-0-(2-nitrobenzyl)uridine is formed. The nitrobenzyl moiety is removed by photolysis at > 320 nm, thus enabling a photolabile protecting group to be used for oligoribonucleotide synthesis.ll3 New methods for introducing heteroatoms into the internucleotidic link have been described. If 5’-U-protected thymidine is treated with diethyl phosphorochloridite, and the resulting phosphite triester condensed with 5’-azido-5’-deoxythymidine in the presence of lithium chloride, the corresponding phosphorornonoamidate diester nucleotide is formed (Scheme 4a).11* An alternative method employs phenyl phosphorodichloridate and 5’-amino-5’-deoxythymidine(Scheme 4b).l15 Reduction of the
HO
0
I
RW-P=O I
NHmT I
R1 = 1-Naphthylcarbamoyloxy ; RB = P(OEt),; R3 = Et
R1 = N,; R2 = P(O)(OPh)CI; R3 = Ph
Reagents : i, (EtO),PCl ; ii, 5‘-azido-5’-deoxythymidine
Reagents : i, PhOP(O)CI,; ii, 5’-amino-Y-deoxythymidine
Scheme 4a
Scheme 4b
5’-terminal azide in Scheme 4b affords the 5’-terminal amino-oligonucleotide. The phosphite-azide coupling is thought to proceed uiu phosphite imine formation. The adduct of thiophosphate and acrylonitrile previously described lo can be coupled to the 3’-hydroxy-group of thymidine. Elimination of acrylonitrile with alkali affords the 3’-U-phosphorothioate, which condenses with 5’-U-tosylthymidine to form thymidine-3’-(5’-S-thymidyl)phosphorothioate (52),llS Oligonucleotides up to the pentamer have been synthesized thus. Protection of the Y-end phosphate during synthesis of an oligonucleotide chain by a group which is selectively adsorbed on to chromatographic supports can greatly and facilitate product separation, and 3-(NN-dimethyla.n1inomethyl)aniline~~~ 2-phenylrnercaptoethan01,~~~ having high affinity for trityl-cellulose and benzoylated DEAE-cellulose, respectively, have been used for this purpose. 113
114 115 116 117
118
E. Ohtsuka, S. Tanaka, and M. Ikehara, Nucleic Acid Res, 1974, 1, 1351. R. L. Letsinger and G. A. Heavner, Tetrahedron Letters, 1975, 147. W. S. Mungall, G. L. Greene, G. A. Heavner, and R. L. Letsinger, J. Org. Chem., 1975, 40, 1659. J. Kresse, K. L. Nagpal, J. Nagyvary, and J. T. Uchic, Nucleic Acid Res., 1975, 2, 1. T. Hata, I. Nagakawa, and Y. Nakada, Tetrahedron Letters, 1975, 467. S. A. Narang, K. Itakura, C. P. Bahl, and N. Katagiri, J . Amer. Chem. SOC.,1974,96, 7074.
Nucleotides and Nucleic Acids
161
In a direct comparison of the application of the ‘diester’and ‘triester’ methods for synthesizing gene fragments of the E. coli lactose operator, the triester method was preferred on account of its higher yields and ease of handling in large-scale syntheses.lls A new phosphorylating agent (53) and new coupling agents (54), ( 5 3 ,
(54) (55)
R’ = R2 = Me R’ = NO,; R2 = H
which are triazolide derivatives, have been used for triester syntheses.120A method has been described for insertion of a 5’-terminal phosphate prior to final deprotection in the triester synthesis.121 The triester method has been used to synthesize oligodeoxynucleotides complementary to the -CpCpA end of tRNA and the -UpGpApA- anticodon region of tRNAPhe, in which each internwcleotide link is additionally esterified by ethanol to give a neutral phosphotriester.lzZThese compounds bind to tRNAPhe, inhibiting amino-acylation in proportion to the strength of the binding constants as measured by equilibrium dia1y~is.l~~ With the restriction that the internucleotidic links adjacent to the 5’- and 3’-ends of the chain may not be phosphotriesters, oligonucleotides containing phosphotriester internucleotide links can act as substrates for polynucleotide kinase and terminal deoxynucleotidyl t r a n s f e r a ~ e . ~ ~ ~ Enzymic Synthesis.-Treatment of ribonucleoside 5’-diphosphates with triethyl ortho-isovalerate and an acid catalyst, followed by hydrolysis, gives a mixture of the 2’- and 3’-isovalerate esters. With a triribonucleoside diphosphate primer, polynucleotide phosphorylase, and manganese ion, these compounds act as singleaddition substrates for stepwise elongation.12s The ester group is removed by methanolic ammonia after each addition. Nucleotides containing modified bases are also acceptable substrates. Polynucleotide phosphorylase from E. coli B will catalyse addition of deoxyribonucleotide 5’-diphosphates to short oligonucleotides (ribo- or deoxyribo-), in the presence of manganese ion. Conditions have been defined for the addition of one or more r e s i d ~ e s With . ~ ~ a~ suitably ~ ~ ~ ~designed primer, homooligonucleotideswith a single residue substitution can be prepared, for studying basepair mismatch effects.lZEPolynucleotide phosphorylase from Micrococcus luteus is K. Itakura, N. Katagiri, S. A. Narang, C. P. Bahl, K. J. Marians, and R. Wu, J. Biol. Chem., 1975,250,4592. 1 2 0 K. Itakura, N. Katagiri, and S. A. Narang, Canad. J. Chem., 1974, 52, 3689. 121 T. Neilson, K. V. Deugau, T. E. England, and E. S. Werstiuk, Canad. J. Chem., 1975,53, 1093. 122 P. S. Miller, J. C. Barrett, and P. 0. P. T’so, Biochemistry, 1974, 13, 4887. 123 J. C. Barrett, P. S. Miller, and P. 0. P. T’so,Biochemistry, 1974, 13, 4897. l Z 4S. A. Narang, K. Itakura, and N. Katagiri, Canad. J. Biochem., 1975, 53, 392. lZ5 G. C. Walker and 0. Uhlenbeck, Biochemistry, 1975, 14, 817. lZ6 S. Gillam and M. Smith, Nucleic Acid Res., 1974, 1, 1631. lZ7S. Gillam, K. Waterman, M. Doel, and M. Smith, Nucleic Acid Res., 1974, 1, 1649. lZB S. Gillam, K. Waterman, and M. Smith, Nucleic Acid Res., 1975, 2, 613. 119
162
Organophosphorus Chemistry
capable of adding two or three deoxyribonucleotide residues to a short oligoribonucleotide primer, forming oligonucleotides containing a single ribonucleotidyl(3’-+5’)-deoxyribonucleotidyl linkage.lZ9 Polyribonucleotides and polydeoxyribonucleotides can be joined in any order using DNA ligase from T4-infected E. coZi.130 Methods of replicating desired oligodeoxynucleotide sequences enzymatically (‘Copy Synthesis’) have beendescribed. Poly(thymidy1icacid) (about 80 residues long) is attached to cellulose via the 3’-terminal phosphate, and phosphorylated at its 5’end using polynucleotide kinase. The oligonucleotide to be replicated is extended at its 3’-end using deoxypolynucleotidyl transferase and dTTP, to give a poly(dT) tail of similar length. Both poly(dT) tracts are then hybridized with poly(dA) and joined using a ligase, to form cellulose-poly(dT)-oligonucleotide. Using DNA polymerase I and a short oligo-(rA) or -(dA) primer, the complementary strand is synthesized, and it can in turn be copied, to give the original sequence.131 Another essentially similar method uses 2’,3’-dideoxyadenosine to block the 3’-terminus of the extended DNA fragment to be copied, thus preventing hydrolysis by the 3’-exonuclease function of DNA polymerase I.132Copy synthesis of mouse globin mRNA has been achieved by complexing oligo(dT)-cellulose (which serves as primer) to the 3’-terminal poly(rA) sequence.133The technique of complexing oligonucleotides with a complementary polynucleotide and joining them to make longer stretches has been described for oligomers of 2’-O-rnethylino~ine-3’-phosphate~~~ (using a water-soluble carbodiimide for joining) and of thymidylic acid (using polynucleotide l i g a ~ e ) . ’ The ~~ minimal requirements that T4 RNA ligase needs to recognize to join two nucleotide fragments have been delineated,136and the extent of these requirements indicates considerable potential for synthesis. The power of the application of enzyme techniques is ably demonstrated in the synthesis of the duplex block polymer d(C15A15) - d(T15G15)-~~‘ Syntheses of several homopolynucleotides containing atypical bases have been reported,13*using polynucleotide phosphorylase from E. coli or M. luteus to polymerize the nucleoside 5’-diphosphates in the presence of magnesium or manganese ions. It has been suggested that the function of the latter ion, which seems to help with poor substrates, is to shift the reaction equilibrium towards polymer formation by removing phosphate from the mixture as the relatively insoluble manganous Copolymers containing thioketopyrimidines have been described, and show very strong vertical stacking interactions.140Homopolymers containing modified I. L. Batey and P. T. Gilham, Biochemistry, 1974, 13, 5395. K. Nath and J. Hurwitz, J . Biol. Chem., 1974, 249, 3680. 131 A. Panet and H. G. Khorana, J. Biol. Chem., 1974, 249, 5213. 132 K. Olsen, T. Gabriel, J. Michalewsky, and C. Harvey, Nucleic Acid Res., 1975, 2, 43. 133 P. Venetianer and P. Leder, Proc. Nat. Acad. Sci. U.S.A., 1974, 71, 3892. 134 S. Uesugi and P. 0. P. T’so, Biochemistry, 1974, 13, 3142. 135A. J. Raae, J. R. Lillehaug, R. K. Kleppe, and K. Kleppe, Nucleic Acid Res., 1975, 2, 423. 136 G. Kaufmann and N . R. Kallenbach, Nature, 1975, 254, 452. 1 3 7 J. F. Burd and R. D. Wells, J. Biol. Chem., 1974, 249, 7094. 138 M. Ikehara, T. Fukui, and S. Uesugi, J . Biochem. (Japan), 1974, 76, 107; T. Kulikowski and D. Shugar, Biochim. Biophys. Acta, 1974, 374, 164; J. Kohlschein, L. Hagenberg, and H. G. Gassen, Biochim. Biophys. Acta, 1974,374,407; K. C . Tsou and K. F. Yip, Biopolymers, 1974, lZ9
130
13, 987. 139 140
J. A. Siedlecki and B. Zmudzka, Acta biochim. polon., 1975, 22, 163. K. H. Scheit and P. Faerber, European J . Biochem., 1975,50,549; P. Faerber, F.E.B.S. Letters, 1974,44, 111.
Nucleotides and Nucleic Acids
163
and sugars142have been found to inhibit oncornavirus function by inhibition of reverse transcriptase. The ‘Paper of the Year’ must surely be that concerning the DINASYN computer program for selecting the optimal synthesis, allowing for both chemical and enzymatic steps, of sequence-definedmacromolecules such as DNA.143DINASYN indicates that Khorana’s gene synthesis, which consumed some 20 man-years of attention time, need only have required 11 years had the optimum path been chosen. ‘A journey of a thousand miles’, said Confucius, ‘begins with one step.’ ‘A journey of five hundred’, he might have added, ‘with a computer program.’ Sequencing.-A kinetic study of the diamine-cztalysed elimination of @-phosphoric esters derived from periodate-oxidized RNA and model substrates has been ~ e p 0 r t e d . The l ~ ~ reaction sequence thought most likely is indicated in Scheme 5 for ornithine. The conjugate acid of the carbinolamine (56) loses water in a general-acidcatalysed dehydration and isomerizes to give the enamine (57). At pH < 8, the dominant path is rapid base-catalysed ,%phosphate elimination, giving (58), which is rapidly oxidized by excess periodate to give adenine, the rates of adenine formation and phosphate elimination running parallel. At pH > 6.5 another process is detectable, ascribed to probable anchimeric assistance of ring opening to give (59), which loses adenine rapidly by periodate oxidation, and phosphate more slowly. The fragments formed on further oxidation of (58) and (59) have not been defined. @-Eliminationfollowing periodate oxidation is the foundation of the post-labelling technique for sequence analysis of non-radioactive RNA fragments,145and optimum conditions for stepwise degradation using this technique have been defined.146 Sequence determination of oligonucleotides frequently depends on end-labelling followed by exonuclease digestion and separation of the resulting array of fragments. The 5’-end may be labelied enzymically by polynucleotide kinase,14’ or chemically, using [32P]orthophosphatedi-imidaz01idate.l~~ The 3’-end of DNA fragments may be labelled using terminal deoxynucleotidyltransferase and an [cc-32P]ribonucleoside t r i p h o ~ p h a t e lor ~ ~2’,3’-dideoxyribonucleoside triphosphate.15*Nearest-neighbour digestion permits identification of the 3’-terminal nucleotide. Such end-labelling has been used to show the position of cleavage and the nucleotide sequence at the cleavage sites of restriction endonu~leases.~~~
141
143 144
145 146 l4’ 148 149
150 l51
P. Chandra, U. Ebener, and A. Gotz, F.E.B.S. Lerters, 1975, 53, 10. E. de Clercq, A. Billiau, J. Hobbs, P. F. Torrence, and B. Witkop, Proc. Nur. Acad. Sci. U.S.A., 1975, 72, 284. G. J. Powers, R. L. Jones, G. A. Randall, M. H. Caruthers, J. H. van de Sande, and H. G. Khorana, J . Amer. Chem. SOC.,1975, 97, 875. M. Uziel, Arch. Biochem. Biophys., 1975, 166, 201. K. Randerath, E. Randerath, L. S. Y. Chia, R. C. Gupta, and M. Sivarajan, Nucleic Acid Res., 1974, 1, 1121. G. Keith and P. T. Gilham, Biochemistry, 1974, 13, 3601. K. S. Szeto and D. Soll, Nucleic Acid Res., 1974,1, 1733; A. Bernardi and C. Gaillard, Analp. Biochem., 1975, 64, 321. E. Rapaport and P. C. Zamecnik, Proc. Nat. Acad. Sci. U.S.A., 1975, 72, 314. A. Bernardi and U. Bertazzoni, Anrrfyt. Biochem., i974, 61, 448. K. Olson and C. Harvey, Nucleic Acid Res., 1975, 2, 319. D. E. Garfin and H. M. Goodman, Biochem. Biophys. Res. Comm., 1974,59, 108.
Organophosphorus Chemistry
164 0
I
OH
I
-OOC--CH-&H~ (56)
J
0
-0
A = Adenine
I 0
I
H
I I
OH
-0
OH
(57)
0 RO -P-O-
I1
I -0
" +
" I
~ OH
~
I
~ I
0
*
I
-0
I
I
I
(CH, 1 3
-ooc-cH--~;JH, I I I
(59)
pH
> 6.5
Scheme 5 5 Analytical Techniques and Physical Methods
Separation and Quantitation.-The ability of dihydroxyboryl-cellulose to complex with cis-diols has been used to separate uncharged tRNA from the amino-acylated Oligo(dT)-cellulose chromatography is valuable for isolation and purifiThese cation of mRNA, in which poly(rA) tracts hybridize to give selective binding.153 152
153
T. M. McCutchan, P. T. Gilham, and D. So11, Nucleic Acid Res., 1975, 2, 853. J. Gielen, H. Aviv, and P. Leder, Arch. Biochem. Biophys., 1974, 163, 146; R. E. Pemberton, P. Liberti, and C. Baglioni, Analyt. Biochem., 1975, 66, 18.
Nucleotides and Nucleic Acids
165
tracts may be detected by hybridization with spin-labelled poly(2’-fluoro-2’-deoxyuridylic The decreased mobility of the spin probe, seen by e.s.r., is a sensitive indicator of the presence of poly(rA). Alternatively, copy synthesis of the poly(rA) The tract using a short primer, dTTP, and DNA polymerase I can be size of the tracts may be determined by hybridization with labelled p ~ l y ( d T )The .~~~ ends of the poly(dT) chain are trimmed with a single-strand-specificnuclease, and the ribopolymer is then hydrolysed with alkali. The size of the poly(dT) remaining is compared against known standards by gel electrophoresis. Structure Probes.-An apparent empirical correlation has been found between chemical shifts and OPO bond angles in phosphate While more data are needed to establish this, the correlation may be useful for predicting structure in solution. The 31Pchemical shifts observed for homopolyribonucleotides are critically dependent on the charged state of the bases.15*It has been demonstrated that tissue metabolite concentrations in whole tissue can be monitored by 31P n.m.r.15aLaser Raman spectroscopy has been used to obtain conformational data in oligo- and poly-nucleotides.160 Radio1ysis.-Several papers have appeared on the radiation-induced cleavage of the sugar-phosphate bond in nucleotides and polynucleotides. y-Irradiation of crystals of 5’-deoxycytidylic acid at low temperature and subsequent examination by e.s.r. shows a radical ascribed to species (6O).lg1Irradiation of an aqueous solution of 8,Scycloadenosine-5’-monophosphate(61), itself formed by y-radiolysis of aqueous
0 \ ]
(62) B = Base
5’-AMP, leads to dephosphorylation.ls2It is thought that the primary process is attack of hydrated electron on the base. Based on the sugar products identified following y-irradiation of aqueous solutions of DNA, it has been suggested that species (62) is formed just prior to strand breakage.163
A. M. Bobst, T. K. Sinha, and Y.-C. E. Pan, Science, 1975, 188, 153. M. J. Modak, S. L. Marcus, and L. F. Cavalieri, J. Biol. Chem., 1974, 249, 7373. 156 S. J. Kaufman and K. W. Gross, Biochim. Biophys. Acta, 1974, 353, 133. 157 D. G. Gorenstein, J. Amer. Chem. Soc., 1975, 97, 898. 158 K. Akasaka, A. Yamada, and H. Hatano, F.E.B.S. Letters, 1974, 53, 339. 159 D. I. Hoult, S. J. W. Busby, D. G . Gadian, G. K. Radda, R. E. Richards, and P. J. Seeley, Nature, 1974, 252, 285. 160 B. Prescott, R. Gamache, J. Livramento, and G. J. Thomas,jun., Biopolymers, 1974,13,1821. 161 D.Krilov and J. N. Herak, Biochim. Biophys. Acta, 1974, 366, 396. lti2 J. A. Raleigh and R. Whitehouse, J.C.S. Chem. Comm., 1975, 305. 1 6 3 M. Dizdaroglu, C. von Sonntag, and D. Schulte-Frohlinde,J. Amer. Chem. Soc., 1975,97,2277. 154 155
9 Ylides and Related Compounds BY S. TRIPPETT
1 Methylenephosphoranes Preparation.-The blue solution obtained on dissolving potassium in HMPT according to the equation: (Me2N)aPO
+
2K +(Me2N)zPO-
+
Me2N-
+ 2K+
has been used in the generation of reactive y1ides.l Wittig olefin syntheses and olefin formation on oxygenation proceed well but reactions with acid chlorides and thioesters gave only moderate yields. Among other syntheses using this base is that of indene shown in Scheme 1. Further examples have appeared of the use of two-phase CH,CH,Br
i ,
CH,$Ph, Br42% Reagents: i, K-HMPT; ii, H,O
Scheme 1
systems in olefin synthesis, with dichloromethane2 or benzene as the organic phase. The yield was maximized by varying the concentration of the aqueous NaOH phase.s Phosphonium salts obtained from poly(dipheny1-p-styrylphosphine)have been used in olefin ~ynthesis.~ The stereospecificity was similar to that using monomeric ylides. The polymeric ylide (1) was used in the synthesis of the dialdehyde (2) as shown.6 Details have appeared of the synthesis of allylidenephosphoranes from methylenetriphenylphosphorane and alkylideneaminoaluminium compounds.6 The crystalline ylide (3) obtained in this way is a 70 : 30 mixture of (E)- and (2)isomers. Reactions.-Halides. Schmidbaur has reviewed his work on the ‘inorganic’ chemistry of ylides.8 Methylenetrimethylphosphorane (4)with the halides ( 5 ) gave the eight1 2
3 4 5
6
H. J. Bestmann and W. Stransky, Synthesis, 1974, 788. S. Hunig and I. Stemmlcr, Tetrahedron Letters, 1974, 3151. W. Tagaki, I. Inoue, Y.Yano, and T. Okonogi, Tetrahedron Letters, 1974, 2587. F. Camps, J. Castells, and F. Vela, Anales de Quim.,1974, 70, 374 (Chem. ASS., 1975, 81, 63 015). J. Y. Wong, C. Manning, and C. C. Leznoff, Angew. Chem. Internat. Edn., 1974, 13, 666. B. Bogdanovid and J. B. Koster, Annalen, 1975, 692. B. Bausch, B. BogdanoviL, H. Dreeskamp, and J. B. Koster, Annnlen, 1974, 1625. H. Schmidbaur, Accounts Chem. Res., 1975, 8, 62.
166
Ylides and Related Compounds
167
CH-0,
(1)
I
CH-o\ CH,-0
,CH\
0
/CH=CH
O C H O
= cross-linked polystyrene
Ph,P=CH,
+ B4AlN=CHCHMeEt
--+
Ph,P=CH-CH-CMeEt
+ B4A1NH2
(3)
membered dipolar species (6) in high yie1d.O The complex (8) previously obtained from (4) and the halide (7) has now been shown to be accompanied by the isomer (9).l0~l1 The cobalt(1v) bromide (10) with (4)gave the complex (1 1).l1#l2 Details have appeared13# l4of the reactions of (4)with Me,PAuCI, Me,PAgCI, and copper(1) chloride to give the analogues of (6). The methyl(phosphine)gold(I) complex (12) with (4) gave a complex (13), of unusual ~tabi1ity.l~ The four-membered bis-ylide (14), previously obtained from (4) and dichlorodimethylsilane,has now been
H. Schmidbaur and H.-J. Fuller, Chem. Ber., 1974, 107, 3674. H. H. Karsch and H. Schmidbaur, Chem. Ber., 1974, 107, 3684. l1 D.J. Brauer, C. Kruger, P. J. Roberts, and Y.-H. Tsay, Chem. Ber., 1974, 107, 3706. l2 H. H. Karsch, H.-F. Klein, C. G. Kreiter, and H. Schmidbaur, Chem. Ber., 1974, 107, 3692. l3 H. Schmidbaur, J. Adlkofer, and M. Heinman, Chem. Ber., 1974, 107, 3697. l4 H. Schmidbaur and R. Franke, Chem. Ber., 1975,108, 1321. lo
Organophosphorus Chemistry
168 (4)
+
(Me,P),NiCL,
m F * Ni
(7)
Ni
4
P < /p
,cqN/cH2P -CH Me2P ,Nj, \ / \ CH, CH,-P-CH, Me2
(4)
+ (Me,P),Me,CoBr (10)
-
Me P '\\
/Me2 CH,
I ,CH,\ /'
CO ,PMe,
Me,P'
I
Me 'CH,
shown to be the kinetically controlled p r 0 d u ~ t . lIt~ rearranges at 25 "C to give the six-membered bis-ylide (15), probably as shown.
(4)
Me, S l x , PMe, (14)
- Me2siYSiM PMe,
(15)
Ylide complexes of PdII have been prepared directly from phosphonium palladates by treatment with sodium acetate in methanol.ls Whereas the ester phosphoranes (16) with the dichloroselenides (17) gave the stable phosphoranes (18), with the cyclic dichloroselenide (19) the salts (20) were obtained.17 Whether the expected (22) or rearranged product (23) resultsl8 from the reaction of ylides with sulphonyl fluorides depends primarily on the relative size of the substituents R1 and R2,rearrangement W. Malisch and H. Schmidbaur, Angew. Chem. Znternat. Edn., 1974, 13, 540. K. Jtoh, H. Nishiyama, T. Ohnishi, and Y . Ishi, J. Organometallic Chem., 1974, 76, 401 ; H. Nishiyama, K. Itoh, and Y . Ishi, ibid., 1975, 87, 129. 1 7 N. N. Magdesieva and R. A. Kyandzhetsian, Zhur. obshchei Khim., 1974, 44, 1708. l8 B. A. Reith, J. Strating, and A. M. van Leusen, J . Org. Chem., 1974, 39, 2728. 15
l6
169
Ylides and Related Compounds
being favoured if R2 is larger than R1. The cyclic intermediates (21) are probably formed via the sulphenes. Ph3P=CHC02R1 + PhR2SeCL, --+ Ph,P=C(SePh)CO,R' (16) (17) R2 = Me or PhCH, (18)
2Ph,P=CHR1
+ RTH,SO,F
R'SO,CH, R2
Ph,P=C
Ph,P=CR2 SO,CH, R1
(22)
(23)
Treatment of the ester phosphoranes (1 6) with organolithiums gives an equilibrium mixture of the lithio-ylide (24) together with the carbophosphorane (25) and lithium Ph3P=CHC0,R'
+ R2Li + Ph,P=CLiCO,JX'
a
Ph,P=C=C=O
(24 1
(16)
Ph,P=C(CO,Me)COPh (26)
+ Me-,SnCl
__f
+ LiOR'
(25)
PhC=CCO,Me
+ Ph,PO,Me,SnCl
(27)
a 1 k o ~ i d e .The l ~ ~latter ~ ~ can be removed with the halides Me3MC1(M = Si or Sn) l 9 or with phenyl isocyanate.20Trimethyltin chloride and the phosphorane (26) gave l9 the acetylenic ester (27) at room temperature!8 A full account has appeared of the alkylation of heterocyclic systems via the reactions of ylides with halogenoheterocycles.21The bis-ylide (28) with dibromo- or di-iodo-methane gave the salts (29), from which the bis-ylide (30) and the cyclohexenone (31) were obtained on sequential hydrolysis.22Dibromoalkanes and (28) gave cycloalkylphosphonium salts from which the stable ylides (32) were obtained on hydrolysis. Allylidenetriphenylphosphorane and the ,B-chloro-acrylates (33) gave the conjugated ylides (34).23Whereas (34; R = H) with benzaldehyde gave a high yield of the expected all-trans-triene, (34; R = Me) with isobutyraldehyde gave comparable amounts of four isomeric olefins. The hydrocarbons (36) of known absolute 19 20
21 22 23
J. Buckle and P. G . Harrison, J . Organometallic Chem., 1974, 77, C22. H. J. Bestmann, R. Besold, and D. Sandmeier, Tetrahedron Letters, 1975, 2293. E. C. Taylor and S. F. Martin, J . Amer. Chem. SOC.,1974, 96, 8095. A. Hercouet and M. Le Corre, Tetrahedron Letters, 1974, 2491. E. Vedejs and J. P. Bershas, Tetrahedron Letters, 1975, 1359.
170
Organophosphorus Chemistry Ph,P=CHCOCH=PPh,
+
+ CH,X, --+
Ph,P=CHCOCHPPh,
(28)
2x-
CH,
(!
H $Ph
Ph, P=CHCO
,
(29)
k,OH-
(Ph3P=CHCOCH,),CH2 (30)
(31;
Br(CH,),Br + (28) n = 2or4
n,+ph,
__f
(CH,), C
n CHCOCH-PPh,
(CK)
OH'*
w \COCH=PPh,
,
Q
(32) Ph, 1'-= CH CH = =CIIC l i =CI KO, Me
(34)
+ CICK==-CHCO,Me
2Ph,P=CHCH=CH,
--+
+
+
Ph,PCH2C11==C11,
(33)
CI-
configuration have been obtained as shown, starting with the optically active dibromides (35).24
q
C
H
I
B
r + 2Ph,P=CH,
-
hPh, Br-
CflCHzBr (35)
J
NaOEt
Curbonyls. The preparation, in the solvent system HMPT-THF (1 : 2), of long-chain olefins containing 94-96 % of the cis-isomer has been described.25Among carbonyl 24 25
H. J. Bestmann and W. Both, Clzem. Ber., 1974, 107, 2926. E. P. Sonnet, Org. Prep. Proced. Internat., 1974, 6, 269.
Ylides and Related Compounds
171
compounds used successfully in olefin synthesis are the pyridines (37),26various purine nucleoside 5'-aldehyde~,~'the aldehydes (38),28(39),20(40),30(41),31and (42),32and the a-halogeno-aldehydes(43)33 and (44).34The predominant isomers from the last were as shown. CHO
A:
Ph
H
EtO,CN----C*\
(37)
OH (39)
OHC, Me,SiC=CCHO
HO
+
Ph,P=CH,
(42)
67%
(43)
R'CHXCHO + Ph,P=C(C0,Rz)CH,R3
(44) R' = H or Me; X = ClorBr
-
CHXR'
The optically active ester formed by asymmetric induction in the reaction of the (R)-phosphorane (45) with the keto-ester (46) has been shown to have the configuration (47) by conversion into the (S)-olefin (48).35Failure of expected olefin synthesis has been reported with the dione (49) 36 and between isopropylidenetriphenylphosphorane and the ketone (50).37Methylenation of the ketone (51) did not take place at room temperature, probably because of enolization, but at -70 "C a 26 27 28 29
3O 31 32
E. Luedtke and R. Haller, Chem.-Ztg., 1974, 98, 371 (Chem. A h . , 1975, 82, 124 567). J. A. Montgomery, A. G. Laseter, and K. Hewson, J. Heterocyclic Chem., 1974, 11, 211. E. Suzuki, R. Hamajima, and S. Inoue, Synthesis, 1975, 192. H. Plieninger, W. Lehnert, D. Mangold, and D. SchmaIz, Tetrahedron Letters, 1975, 1827. E. R. Biehl and P. C. Reeves, Synthesis, 1974, 883. J. V. Frosch, I. T. Harrison, B. Lythgoe, and A. K. Saksena, J.C.S. Perkin I, 1974, 2005. T. R. Boronoeva, N. N. Belyaev, M. D. Stadnichuk, and A. A. Petrov, Zhur. obshchei Khin., 1974,44, 1949.
33 34 35
36 37
A. Schmidt and G. Kobrich, Tetrahedron Letters, 1974, 2561. P. L. Stotter and K. A. Hill, Tetrahedron Letters, 1975, 1679. H. J. Bestmann, E. Heid, W. Ryschka, and J. Lienert, Annalen, 1974, 1684. R. K. Hill and D. W. Ladner, Tetrahedron Letters, 1975, 989. H.M. McGuire, H. C. Odom, jun., and A. R. Pinder, J.C.S. Perkin I, 1974, 1879.
1 72
Organophosphorus Chemistry
0 (49)
B-3~ ~
e
~
O
b
-
(5 2) \
Q c
~
-+ ~ Ph,*Me Br-
CH,=CH(CH,),OH (53) 80%
,/*
".\
)/
/'
\
%x
DMSO MeSOCH,Na>
OHC(CH,),O-
/'
(54)
97 % yield of the olefin was ~ b t a i n e dAttempted .~~ methylenation of the ketone (52) in DMSO gave only the olefin (53), presumably formed via the aldehyde (54) as sh0wn.3~In ether, and with butyl-lithium as base, 20% of the expected olefin was obtained. It has been suggested40 that the reaction of allylidenephosphoranes at the yposition in Michael additions to ap-unsaturated ketones, first observed by Buchi, takes place via normal addition followed by [3,3]-sigmatropic rearrangement as shown in Scheme 2.
Scheme 2 s8 39 *O
L. N. Mander, J. V. Turner, and B. G. Coombe, Austral. J. Chem., 1974, 27, 1985. B. Janistyn and W. Hansel, Chem. Ber., 1975, 108, 1036. J. R. Neff, R. R. Gruetzmacher, and J. E. Nordlander, J. Org. Chem., 1974, 39, 3814.
Ylides and Related Compounds
173
Adamantanetkione ( 5 5 ) with methylenetriphenylphosphorane gave high yields of the thiiran (56) and phosphine.*lWith the four-membered dithione (57), ring opening followed by proton transfer gave the stable ylide (58).
+ Ph,P=CH,
+ Ph.$=CH,
+ Ph,P
__f
Me,CHCSCMe,CSCH=PP& (58)
S (57)
A full account has appeared of the reactions of ylides with reactive Treatment of esters with methylenetriphenylphosphorane in DMSO followed by water converts the ester group into an isopropylidene The obvious possibilities have been eliminated as intermediates, and the mechanism of this intriguing conversion is uncertain. Miscellaneous. Ketenimines (59) are obtained from isocyanates and ylides which do not have an cr-hydr~gen.~~ Benzylidenetriphenylphosphoraneand the trinitriles (60) gave the iminophosphoranes (61) and/or (62) depending on the nature of the substituents and the condition^.^^ Both are probably formed via the same intermediate (63), the rearrangement shown leading to (62).
R' CN
I I I t CN CN
R2-C-C-R3
(60)
+
R1 CN
I
I
Ph,P=CHPh
41 42
43 44 45
A. P. Krapcho, M. P. Silvon, and S. D. Flanders, Tetrahedron Letters, 1974, 3817. M. Le Corre, Bull. SOC.chim. France, 1974, 2005. A. P. Uijttewaal, F. L. Jonkers, and A. van der Gen, Tetrahedron Letters, 1975, 1739. P. Froyen, Actu Chem. Scand. ( B ) , 1974,28, 586. C. Gadreau and A. Foucaud, Tetrahedron Letters, 1974, 4243.
1 74
Organophosphorus Chemistry
Methylenetriphenylphosphorane and the aryl cyanate (64) gave46the cyanomethylenephosphorane(65), in contrast with a previous report 47 which described the formation of the dicyanomethylenephosphoranein this reaction. The production of amides
Ph,P=CH,
+ p-MeC,H,OCN (64)
-
Ph,P=CHCN
f
p-MeC,H,OH (65)
or esters on treatment of the stable ylides (66) with nitrous acid in the presence of mines or alcohols, respe~tively,~~ may involve intermediate acyl cyanides formed as in Scheme 3. Ph,P=CHCOR
i ,Ph$-CHCOR
(66) R = Me,Ph, or OR'
I NO
_.+.
Ph,?-CCOR 6-N
II
Ph,PO + RCOCN Reagent: i, HNO,
Scheme 3
2 Phosphoranes of Special Interest Copper bronze is an effective catalyst in the formation of the ylides (67) from diazocyclopentadienesand triphenylph~sphine.~~ The phosphole ylide (68), obtained in a similar way, decomposes at 175 "C in diphenyl ether to give 7,lO-diphenylfluoranthene, perhaps via the elusive 1,Zacenaphthyne (69).50 The ylide (70) reacts with carbon disulphide with transfer of the silyl group to give the isomeric ylides (71) and (72).51Similar transfers occur in reactions with phenyl isocyanate and isothiocyanate. The proportion of trans-isomer present in solutions
413 H. 47
49 60
S1
J. Bestmann and S . Pfohl, Annalen, 1974, 1688. D. Martin and H.-J. Niclas, Chem. Ber., 1967, 100, 187. S.Yamada and Y . Takeuchi, Chem. andPharm. Bull. (Japan), 1974,22,634 (Chem. Abs., 1974, 80, 145 701). B. H. Freeman and D. Lloyd, Tetrahedron, 1974, 30, 2257. J. I. G. Cadogan, R. J. Scott, and N. H. Wilson, J.C.S. Chem. Comm., 1974,902. K. Itoh, H. Hayashi, M. Fukui, and Y . Ishi, J. Organometallic Chem., 1974, 78, 339.
Ylides and Related Compounds
175°C
150 'C
+
Ph
175
OPh
+ [PhPOJ
cu
64%
Ph
of the alkoxythiocarbonylphosphoranes(73) increases with increasing size of the group R and with increasing solvent polarity.5aAlkylation of (73) takes place only on sulphur. PhMe,P=CHSiMe,
PhMe,P
a
\c/
+
I
(70)
I
C
s// 'SSiMee3 Ph,P=CH-C,
H
Me,SiS
2 'OR
(73) R = Me,Et,orPri
Nitrosobenzene and triphenylvinylphosphonium bromide give the salt (74), which with base gives an equilibrium mixture of the quinquecovalent phosphorane (77) and the cis- (76) and trcfns-ylide (75), the constitution of which varies with solvent and ternperat~re.~~ The salt (74) takes part in normal olefin synthesis to give unsaturated nitrones, e.g. (78). Insertion of dimethyl acetylenedicarboxylate into the cumulene ylides (79) gives the phosphoranes (80).54Ylide (79; X = NPh) with aromatic aldehydes gives either the highly coloured dimers (83) of the expected imines (81) or the 1 : 1 adducts (82) of 6a
63 64
H. Yoshida, H. Matsuura, T. Ogata, and S. Inokawa, Chem. Letters, 1974 1065. R. K. Howe, J. Org. Chem., 1974, 39, 3501. H. J. Bestmann, G . Schmid, and D. Sandmeier, Angew. Chem. Innternat. Edn., 1975, 14, 53.
176
0rganophosphorus Chemistry Ph,kH=CH,
Br-
+ PhNO
__f
Ph,kH=CHN(OB)Ph
Br-
(74)
p.4 .\
(75)
(7 7)
C0,Me Ph3P=C=C=X + MeO,CC~CCO,Me (79) X = S or NPh
1
_j
Ph,P=C-C=C=C=X
1
C0,Me (80)
NPh
(79;
X = NPh) + ArCHO
* [ArCH=C=C=NPh]
(79),
(81) with (79; X = NPh), depending on the ratio of the reactankB5Benzil and fluorenone gave unreactive adducts analogous to (82). Among other noteworthy ylides were (84),66 (85),57and (86),5s obtained as shown. The last did not react with benzaldehyde in refluxing THF. 55 56
57
H. J. Bestmann and G . Schmid, Angew. Chem. Internat. Edn., 1974, 13, 473. Japan. Kokai 74, 110 650 (Chern. A h . , 1975, 82, 139 691). K. Burger and A. Meffert, Annulen, 1975, 317. H. Hauptmann, TetrahedronLetters, 1974, 3593.
177
Ylides and Related Compounds
ButoBut Na
+ Ph,PCl,
Et,Nr
BU'
$(But
PPh,
(84)
R'CH=CH-N=C
(CF, ),
-+ R:P --+
P=CR' -CH=NCH(CF,), (85)
(ButC=C),CHBr
+
+ BU~C-C-C=C=CHBU~
Ph,P
BuLi
(Bu'C=C),C=PPh,
I
(86)
'PPh, Br-
3 Selected Applications of Ylides in Synthesis General.-The synthesis of heterocycliccompounds using ylides has been reviewed.sg Strained bridgehead olefins have been synthesized using intramolecular Wittig olefin reactions. They include bicyclo[3,3,l]non-l(2)-ene,60bicyclo[4,2,l]non-l(8)ene (87),"l and bicyclo[3,2,l]oct-l(7)-ene,62the last being trapped as isomeric adducts
(87)5 7 %
with diphenylisobenzofuran. In these examples the ylides for cyclization were generated in the conventional way from the phosphonium salts; they may also be obtained by the technique associated with Schweizer, as shown, e.g., in Scheme 4. Spiroannelation of the 2-formylcycloalkanones (88) has been achieved using the Ylides are also intermediates in the cyclopropylphosphonium salt (89) as synthesis of cyclohexa-l,3-dienes(91) from the butadienylphosphonium salt (90) and enolate anions. 64 Cyclohexenones (93) are obtained from metallated phenacylidenetriphenylphosphorane (92) and ab-unsaturated ketones, as shown in Scheme 5.6s 59
E. Zbiral, Synthesis, 1974, 775.
60
K. B. Becker, Chimiu (Switz.), 1974, 28, 726.
K. B. Becker, Tetrahedron Letters, 1975, 2207. W. G. Dauben and J. D. Robbins, Tetrahedron Letters, 1975, 151. 133 W. G. Dauben and D. J. Hart, J. Amer. Chem. SOC.,1975,97, 1622. e4 P. L. Fuchs, TetrahedronLetters, 1974,4055; G . Buchi and M. Pawlak, J. Org. Chem., 1975,40,
61 62
100. 66
C. Broquet, Tetrahedron, 1975, 31, 1331.
Organophosphorus Chemistry
178
1
[qco
*::Ie
i i Ph
C0,Me
19% Reagents : i, NaH-THF; ii, diphenylisobenzofuran Scheme 4
30-44%
Naphthalene has been obtained from glyoxal and the bis-phosphonium salt (94) as shown.se The tetralone (96) was formed 6 7 from the ylide (95) and diphenylcyclopropenone in an interesting sequence of reactions involving expulsion of phosphine from the initial adduct and cyclization of the resulting keten. Among other interesting phosphoranes used successfully in olefin synthesis are 67
A. Schoenberg, E. Singer, and H. Schulze-Pannier, Synthesis, 1974, 723. Y. Tamura, T. Miyamoto, H. Kiyokawa, and Y. Kita, J.C.S. Perkin I , 1974, 2053.
1 79
Ylides and Related Compounds Ph,P.=CHCOPh
(92) + R'RT=CRWCH,R!
Him : Ph3P=CLiCOPh
-
(92)
PhCoC-CR1R2-~R~OCH2R
II
-PPh,
1 R4
R' R2
R4
I
R J3-p h (
ph%3
R' R2
R
R2
(93) Scheme 5
35 %
(94)
+
"pPh
CH=PPh, (95)
(96) 40%
Organophosphorus Chemistry
180
(97)
R
PbP=CHCOR = CI-I$r,CH,OMe,CI-LJ)Ph, CHCJ, CH(OEt),, CO,Et, or CONH,
G
Ph,P=CXCOMe (98) =
x
o pph, (99)
fi3%C&), CO, H X(100)
Ph,kH,OR X-
(103) R =
P&{(CH,),SO,Na
(101) n = 5-8
(102)
P h 3 k H , 0
0
BI-
(104)
' C H 2 O 0'
CH,OCH,OMe, or CH,OR'
Bf
y 3 C H 2 $ P h 3 X-
o / (105)
(95),68(97),60(98),'O and (99) and and those derived from the salts (101),72 (102),73(103),74(104),75and (105).76Olefination using the ylides Ph3P=CHSR1 has been used as the first stage in synthetic sequences leading to the homologation of aldehydesunder mildly basic conditions 7 7 and to the conversion of aldehydesR2CH0 into R2CH(SR1)CH0.78 Oxygenation of the bis-ylide (106) in DMSO gave the cis-olefin (107).79
(107) 22% 68
Y.Tamura, T. Miyamoto, and H. Taniguchi, Chem. and Ind., 1974, 772.
69
M. Le Corre, Bull. SOC.chim. France, 1974, 1951. A. Gorgues and A. Le Coq, Compt. rend., 1974,278, C, 1153. D. W. Knight and G. Pattenden, J.C.S. Perkin I, 1975, 635. A. S. Kovaleva, V. M. Bulina, L. L. Ivanov, Y.B. Pyatnova, and R. P. Evstigneeva, Zhur. org. Khim., 1974, 10, 696. Y. Iguchi, S. Kori, and M. Hayashi, J. Org. Chem., 1975,40, 521. H. Schlube, Tetrahedron, 1975, 31, 89. R. K. Bentley, C. A. Higham, J. K. Jenkins, E. R. H. Jones, and V. Thaller, J.C.S. Perkin I,
70
71 72
73 74 75
1974, 1987. 76 77
78 79
P. Bravo, A. Ricca, and 0. Vajna de Pava, Chimica e Industria, 1974,56,25 (Chem. Abs., 1974, 61, 13419). I. Vlattas and A. 0. Lee, Tetrahedron Letters, 1974, 4451. H. J. Bestmann and J. Angerer, Annalen, 1974, 2085. J. A. Deyrup and M. F. Betkouski, J. Org. Chem., 1975, 40,284.
181
Ylides and Related Compounds
Natural Products.-An important step in the synthesis of optically active disparlure was the reaction of the lactol (108) with an excess of the ylide (109).80Other sex
+
3.5 Ph,P=CHCHMe, (109)
OH (108)
HO ='
O
I
77%
pheromones synthesized with the aid-of ylides include those of the pink bollworm8' and the Egyptian cotton leafworm.82The salt (110), derived from triacetic acid lactone, has been used in the synthesis of tetra-acetic acid lactone and other acetog e n i n ~Olefination .~~ with keten at room temperature gave the allene (111) in good yield.
(1 10)
(111) 68%
(112) R', R2 = H o r D 80
82
8s
S. Iwak, S. Marumo, T. Saito, M. Yamada, and K. Katagiri, J. Amer. Chem. SOC.,1974, 96, 7842. P. E. Sonnet, J. Org. Chem., 1974, 39, 3793. D. R. Hall, P. S. Beevor, R. Lester, R. G. Poppi, and B. F. Nesbitt, Chem. andZnd., 1975,216. J. L. Bloomer, S. M. H. Zaidi, J. T. Strupczewski, C. S. Brosz, and L. A. Gudzyk, J. Org. Chem., 1974, 39, 3615.
7
0rganophosphorus Chemistry
182
Among other syntheses involving the use of ylides in key steps are those of natural polyacetylenes from the fungus Fistulina pallida 84 and from Trachelium caeruleum L.,75 y-bi~abolene,~~ 2-rethrolones and 2 - r e t h r o n e ~and , ~ ~the geometrical isomers of the triene C5H11(CH=CH)3H from the essential oils of Galbanum and the Hawaiian seaweed Dicty~pteris.~’ Carotenoids include methoxylated aromatic carotenoids,88 3,3’-dihydroxyi~orenieratene,~~ (2R,2’R)-2,2’-dimethyl-~,~-carotene, lycopen-20-a1 and rh0dopin-20(20‘)-al,~land specifically deuteriated carotenoids, using, among others, the salts (1 12),@, Showdomycin (114; R = H) was obtained by debenzylation of (114; R = PhCH,), prepared from the or-keto-ester (113) and the amido-phosphorane.Qs H
CO,Me
ROC-
I
CO
W
RO OR (113) R = PhCH,
+
Ph,P=CHCONH,
-+
RociY RO OR
(114)
3-Deoxy-3-C-methyl sugars have been synthesized using the ylide (115), as shown.Q* Further examples have appeared of the reactions of protected keto-sugars with simple ylides in conventional olefin ~ y n t h e s e s . ~ ~ M. Ahmed, G. C. Barley, M. T. W. Hearn, E. R. H. Jones, V. Thaller, and J. A. Yates, J.C.S. Perkin I , 1974, 1981. 85 D. J. Faulkner and L. E. Wolinsky, J. Org. Chem., 1975, 40, 389. 86 G. Pattenden and R. Storer, J.C.S. Perkin I, 1974, 1603. 87 F. Naf, R. Decorzant, W. Thommen, B. Willhalm, and G. Ohloff, Helu. Chim. Acta, 1975, 58, 1016. 8 8 N. Okukado, Bull. Chem. SOC. Japan, 1974, 47, 2345. 89 N. Okukado, T. Kimura, and M. Yamaguchi, Mem. Fac. Sci. Kyushu Uniu., 1974, 9, C, 139 (Chem. Abs., 1974, 81, 152 447). 90 A. G. Andrewes, S. Liaaen-Jensen, and G. Borch, Acta Chem. Scand. ( B ) , 1974, 28, 737. 91 0. Puntervold and S. Liaaen-Jensen, Acta Chem. Scand. ( B ) , 1974, 28, 1096. 92 H. Brzezinka, B. Johannes, and H.Budzikiewicz, Z. Naturforsch., 1974, 29b, 429. 93 G.P. Appl. 2 358 645!1974 (Chem. Abs., 1974, 81, 105 908). 94 J. M. J. Tronchet, X. T. Nguyen, and M. Rouiller, Carbohydrate Res., 1974, 36, 404. Q5 J. M. J. Tronchet and J. Tronchet, Carbohydrate Res., 1974, 33, 237; J. M. J. Tronchet and D. Schwarzenbach, ibid., 1974, 38, 320.
84
Ylides and Related Compounds
183
Macrocyclic Compounds.-Terephthalaldehyde and the bisphosphonium salt (116) gave the [24]annulene (117).@6 Ylides have been used for the construction of amdiacetylenes for subsequent oxidative cyclization; bisdehydro-oxa[l3]- and [15]annulenes and their thia-analogues and bisdehydrothia[l7]annulenes @ g have been prepared in this way. Some of these syntheses, e.g. of (118), involved the simultaneous reaction of a bis-ylide with two different aldehydes.@8 @'
@ *
/===/
2BrCHO
CH,PPh.,
(117) 15%
(118) 4.5%
Full accounts have been given of the syntheses of epoxy-bridged [19]- and [21]annulenones,loo of 3-thiabicyclo[3,2,O]hepta-l,4-diene,lo1 and of (P)-( )-pentahelicene.lo2
+
4 Selected Applications of Phosphonate Carbanions Phase-transfer catalysis has been applied successfully to olefin synthesis with phosphonate car bani on^,^^^^ lo* using dichloromethane as the organic phase and quaternary ammonium salts or crown ethers as the transfer agents. The ratio of (E)to (2)-isomers produced varies with the ~ a t a l y ~Otl.e~h ~synthesis ~ with 2-substituted cyclohexanonesand the ester phosphonates (R10)zPOCH2C02R2 is successful only if the substituent can readily become axia1.1°5 Thus (119) and (120) are unreactive while (121) and (122) are reactive. Olefin formation from (123) is slow and involves base-catalysed isomerization to the 2-axial isomer. B. Thulin, 0. Wennerstrom, and H.-E. Hogberg, Acta Chem. Scand. ( B ) , 1975, 27, 138. R. L. Wife and F. Sondheimer, J. Amer. Chem. Suc., 1975,97, 640. 98 R. L. Wife, P. J. Beeby, and F. Sondheimer, J. Amer. Chem. SOC.,1975, 97, 641. 99 R. L. Wife and F. Sondheimer, TetrahedronLetters, 1975, 195. 100 T. M. Cresp and M. V. Sargent, J.C.S. Perkin I, 1974, 2145. 101 P. J. Garratt and D. N. Nicolaides, J. Org. Chem., 1974, 39, 2222. 102 H.J. Bestmann and W. Both, Chem. Ber., 1974, 107, 2923. 103 C. Piechucki, Synthesis, 1974, 869. 104 M. Mikolajczyk, S. Grzejszczak, W. Midura, and A. Zatorski, Synthesis, 1975, 278. lo6 K. E. Harding and C.-Y.Tseng, J. Org. Chem., 1975, 40, 929. 96
97
184
Organophosphorus Chemistry 0
(119)
(120)
(121)
(122)
(123)
Among phosphonates used successfully in olefin synthesis were (124),lo6(125),lo7 (126),37(127),Io8(128),lo9(129),110(13O),l1l(131),11*and (132).lI3With nitrosobenzene the last gave the enamine (133). (MeO),P(O) CH,COCH$H,CH=CMeCH,O
(PhO),P(O) CHCIC, &NO,*
(EtO),P(O) CHMeSMe
0"'
NHCOCH,P(O) (OEt),
(130) R' = H OK Me
106 107
108 109 110 112 113
(EtO),P(O) CHCNCR'RTN
(1311
W. G. Dauben, G. H. Beasley, M. D. Broadhurst, B. Muller, D. J.Peppard, P. Pesnelle, and C. Suter, J. Amer. Chem. SOC.,1974, 96, 4724. H. Zimmer, K. R. Hickey, and R. J. Schumacher, Chimiu (Switz.), 1974, 28, 656. S. F. Martin and R. Gompper, J. Org. Chem., 1974, 39, 2815. A. Wu and V. Snieckus, Tetrahedron Letters, 1975, 2057. D. Danion and R. Carrie, Buff.SOC.chim. France, 1974, 2065. J. H. Sellstedt, J. Org. Chem., 1975, 40, 1508. E. G . Yushko, D. G. Pereyaslova, and V. V. Beznichenko, Stsintill. Org. Lyuminofory, 1972,47 (Chem. Abs., 1975, 82, 124 240). T. Minami, I. Niki, and T. Agawa, J. Org. Chem., 1974, 39, 3236.
Ylides and Related Compounds
185
An intramolecular olefin synthesis with the steroidal phosphonate (134) gave the cardenolide (135).l14 Whereas the trans-phosphonate (1 38) was formed in high yield when the protected arabinose (136) was treated with the anion of the diphosphonate (137), (136) with the lithium salt of the silylphosphonate (139) gave cis- and trunsphosphonates in a ratio of 2 : 1.115
CHO (138) 87%
Cyclopentenones are formed on cyclization of BE-diketo-phosphonates.'lb cisJasmone (140) has been synthesized in this way. B-Hydroxyphosphonateshave been obtained from protected keto- and aldehydo-sugars and the lithiated phosphonate (141).l17
RCHO + LiCH,P(O) (OMe), (141) 114 115 116 117
-
RCH(0H) CH,P(O) (OMe),
G. Kruger, Canad. J . Chem., 1974, 52, 4139. H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1732. R. D. Clark, L. G. Kozar, and C. H. Heathcock, Synthetic Comm., 1975, 5 , 1. H. Paulsen and W. Bartsch, Chem. Ber., 1975, 108, 1229.
186
Organophosphorus Chemistry
Asymmetric induction gave the (R)-allenic esters (144) starting from the (S)phosphinate (142) and the ketens (143).l18 With 2-methylcyclohexanone, (R)phosphinate (142) gave the (E,R)- and (2,s)-unsaturated esters (145). Pure transolefins (147) were obtained on lithium aluminium hydride reduction of the allylphosphonates (146) even if these were not isomerically pure.11e OMe
I II
PhPCH,CO,Me + PhRC=C=O -+ PhRC=C=CHCO,Me (143) R = MeorEt (144) 0 ,
(142)
MeR'C=CHCH,P(O)
(OEt),
i. BuLi %,
px
*
MeR'C=CHCHR'P(O)
(OEt),
(146)
MeR'CH >=C H
/H 2R'
Both aziridine (150; R = H) and enamine (151) were obtained when the 1pyrroline 1-oxide(148; R = H) was treated with the phosphonate carbanion (149). Only the aziridine was formed from (148; R = Me).120The nitrone (152) with the carbanion (149) gave the two aziridines (153) and (154).lz1The former must arise from tautomerism of (152) to the isomeric nitrone (155) followed by reaction with (149).
(150) 62% 118 119 120 121
(151) 18%
S. Musierowicz, A. Wrbblewski, and H. Krawczyk, Tetrahedron Letters, 1975, 437. K. Kondo, A. Negishi, and D. Tunemoto, Angew. Chem. Znternat. Edn., 1974, 13, 407. D.St. C. Black and V. C. Davis, J.C.S. Chem. Comm., 1975, 416. E. Breuer and I. Ronen-Braunstein, J.C.S. Chem. Comm., 1974, 949.
187
Ylides and Related Compounds PhCH=NMe
4 0
dCO'"' N
+ (149)
t.
CH,Ph (153) 40%
(152)
(154) 20%
I
J.
+
PhCH,N=CH, 0 (155)
Whereas the carbanions (1 56) reacted with phenyl isocyanate and isothiocyanate to give the expected phosphonates (157), the initial product from the dimethyl phosphonate carbanion (1 58) and phenyl isothiocyanate was subsequently Smethylated to give (159).123 (RO),P(O)cHX + PhNCY -+ (RO),P(O) CHXC(Y) NHPh
-
(156) X = CNor C0,Et Y = 0 or S (MeO),P(O) CHCN + PhNCS (158)
(157)
(MeO),P(O)C(CN)=C(SMe)NHPh (159) 50%
l a a Z. Hamlet and W. Mychajlowskij, Chem. and I d . , 1974, 829.
10 Phosphazenes BY
R. KEAT
1 Introduction A feature of the chemistry of this group of compounds is the rapidly expanding patent literature. The phosphazenes appear to have many potential applications in the production of elastomers and rubbers as well as flameproofingagents. However, there have been no particularly noteworthy developments in the basic chemistry of these compounds. 2 Synthesis of Acyclic Phosphazenes
From Amides and Phosphorus(v) Halides.-The use of hexamethyldisilazane in the extension of phosphazene chains has been further demonstrated? CbPO
+ (Me3Si)zNH
__+
ClzP(O).NH.SiMea
+
MeaSiCl
Further reaction of C12P(0)- N=PC13 with hexamethyldisilazane occurs at the =PC13 group and enables up to three -N=PC12 units to be introduced, giving Cl 2P(0)(N=PCl,)3C1. Surprisingly, silyl derivatives such as CI2P(0)(N=PCl2), NH. SiMe, do not undergo cyclization (see ref. 80). Thiophosphoryl analogues of these compounds, Cl,P(S)(N=PCl,),, 2C1, have been prepared by the reaction of phosphorus(lr1) trichloride with chlorine, ammonia, and sulphur in chlorobenzene solution. The silylamino-derivative (Me,Si),N - PF2 and phosphorus pentafluoride form a fluorophosphazene at ambient temperatures:3
-
(Me3Si)2NPF2
+ PF5
__+
F3P=NPFi
+ 2Me3SiF
Separation of F3P=NPF2 has been achieved by complexation with a bicycloheptadienemolybdenum tetracarbonyl to give c~s-[(F,P=NPF~)~Mo(CO),].It is worth noting that the 1°F n,m.r. spectrum of F3P=NPF2 suggests that there is restricted rotation about the =N-PF, bond at -30 "C. It is well known that the Kirsanov reaction of anilines and phosphorus pentachloride results in monophosphazenes, ArN=PCl 3, which may dimerize to form cyclophosphazanes (1). The tendency to dimerize, as shown by 31Pn.m.r., has been L. Riesel and R. Somieski, 2. anorg. Chem., 1975,411, 148. W.Bewert, V. Kiener, and G. Wunsch, Ger. Offen. 2 234 373 (Chem. Abs., 1974,81,51 77611). G.-V. Roschenthaler, R. Schmutzler, and E. Niecke, Z . Nurur-orsch., 1974,29b,436.
188
189
Phosphazenes
Ar
N
correlated4with pKa data for the parent anilines. Only the most weakly basic anilines gave monomeric phosphazenes. Preparative details for the known salt-like phosphazenes [Ph,P=N=PPh,]+Cland [Phz(H2N)P=N-P(NH2)Ph2]+C1- have appeared. From hides and Phosphorus(rI1) Compounds.-Phosphazenes obtained by the reaction of phosphites, or of amino-phosphines, with alkyl and phenyl azides, e.g.
+ MeN3+(Me0)3P=NMe + Nz (Me2N)sP + PhN3 +(Me2N)3P=NPh + N2 (Me0)3P
have been the subject of i.r., mass, and n.m.r. spectroscopic studies.' The latter show that the barrier to rotation around the P=N bond is low, probably < 7 kcal mol-l. The intermediates (Me,N),P=N.N=NR (R = Me or Ph) have been isolated,* and their n.m.r. spectra and thermal decomposition studied. The kinetic data obtained ( M e N+ - p P h are consistent with the formation of an intermediate , , during N-N decomposition. The use of diphosphinesO (Scheme 1) and diphosphinoalkaneslO (Scheme 2) as substrates for reaction with trimethylsilyl azide has been explored.
R,P-PR,
II N - SiMe,
RIP-PR, i i ,
II II
r s
.._
R,P-PR,
II II
0 s
I
/
SiMe,
R,P-PR,
(R = Me, Et, or Pr")
\
Reagents: i, MeaSiNs; ii, SS; iii, HzO
Scheme 1 H. A. Klein and H. P. Latscha, 2. anorg. Chem., 1974, 406, 214. J. K. Ruff and W. J. Schlientz, Inorg. Synth., 1974, 15, 84. M. Bermann and J. R. Van Wazer, Znorg. Synth., 1974, 15, 199. H. Goldwhite, P. Gysegem, S. Schow, and C. Swyke, J.C.S. Dalton, 1975, 12. H. Goldwhite, P. Gysegem, S. Schow, and C. Swyke, J.C.S. Dalton, 1975, 16. R. Appel and R. Milker, Chern. Ber., 1974, 107, 2658. lo R. Appel and I. Ruppert, Z . anorg. Chem., 1974,406, 131.
Organophosphorus Chemistry
190
Ph,P(CH,),, PPh,
II
(n
II
N
N
SiMe,
SiMe,
I
/
Reagents: i, MesSiNa; ii, HCl; iii, PF5;iv, PhzPFa-2 ( x = 0 or 1)
Scheme 2
Phosphazenes with potential herbicidal and defoliating activity have been prepared1' from the reactions of phosphites with phosphinothioyl azides : (R10)3P
+
N3P(S)(OR2)2+(R10)3P=N *P(S)(ORa)2 (R1 and R2 = alkyl or Ph)
+ Na
Compounds of this type are known to undergo a number of rearrangements, all of which involve P=O bond formation, but this was not observed in these cases. The triphenylphosphazenyl derivatives Ph,P=N * SO, OSiMe, le and Bh,P=N .N= CH -CO- CH,(CHO,CPh),CH,O,CPh (a hexulose) have also been obtained from triphenylphosphine and the corresponding azides. Other Methods.-Last year, the first example of a phosph(~r~)azene, (Me,Si),N. P= N-SiMe,, was reported. It now appears that compounds of this type are less reactive with a =NBut substituent:la
-
PBr3
-LiBr
+ LiNButSiMe3 +But(Me3Si)NP=NBuf - Me,SiBr
This phosphazene is only slowly oxidized in air and can be converted into an isolable sulphide14and selenide,ls But(Me,Si)N .P(X)(=NBut) (X = S or Se), the first examples of such species. Furthermore, variable-temperaturelH n.m.r. spectroscopy shows that the Me,Si group undergoes an intramolecular shift at room temperature, and that an intermolecular exchange process may be operative also. 11 12 13 14 15
A. A. Khodak, V. A. Gilyarov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1974,44,24. H. R. Kricheldorf and E. Leppert, Synthesis, 1975, 49. M. L. Wolfrom, N. Kashimura, and D. Horton, Carbohydrare Res., 1974, 36, 21 1. 0. J. Scherer and N. Kuhn, Angew. Chem. Internal. Edn., 1974, 13, 811. 0. J. Scherer and N. Kuhn, J. Organometallic Chern., 1974, 78, C17.
Phosphazenes
191
The bis(trimethylsily1amino)-analogue, (Me,Si),N - P=NBut, has been obtained l6by the reactions: heat,
(Mc,Si)ButNLi,
(Me3Si)zN.PCh
-LiCI
(Me3Si)zN PCl .NButSiMe3
____+
- Me,SiCl
(Me3Si)zN-P=NBut
This phosphazene also forms a stable sulphide and selenide. Reactions with methanol and, subsequently, carbon tetrachloride, generate a phosph(v)azene: (Me3Si)zN * P =NBut
MeOH
CCI,
+(Me3Si)zN(MeO)PNHBut +Me3SiButN(MeO)C1P=NSiMer
The silyl group is clearly fairly labile (see also refs. 43 and 45 for reactions of these compounds). This work has a bearing on recent attempts to establish the intermediacy of reactive phosphazenes (or metaphosphorimides). Thus, photolysis of the azide (2) in the formation of (4), possibly via the metaphosphorimide (3).
However, the possibility of (4) being formed via a nitrene intermediate has not been ruled out. An intermediate of similar structure may be invoked in the ring expansion of (5). Other workerslS have since reported studies on the photolysis of (6), which gave (8) as a major product. No matter which isomer of (6) was used, the same mixture of cis- and trans-isomers of (8) was obtained, implicating an intermediate (7) Me
(5 )
(61
(7)
(8)
with a planar distribution of bonds about phosphorus. Several other products were separated by high-pressure liquid chromatography and their significance was discussed. The presence of the intermediate (9) has been implicatedlBby a ‘three-phase test’. It is believed that (9) is generated from an insoluble polymer, passes through a
l7 18 19
0. J. Scherer and N. Kuhn, J. Orgunometallic Chem., 1974, 82, C3. M. J. P. Harger, J.C.S. Perkin I , 1974, 2604. J. Wiseman and F. H. Westheimer, J. Amer. Chem. SOC.,1974,96,4262. J. Rebek and F. Gavina, J. Amer. Chem. Sac., 1975,97, 1591.
192
Organophosphorus Chemistry
solution, and phosphorylates an amine that is bound to a second polymer. The very reactive salt-like compound [Me,N-P-NMe,]+ A1Cl4- has been obtained2O from the reaction of (Me,N),PCl (or Me,N -PCl,) with AlCl,. The occurrence of relatively strong (2p3p)mbonding in the cation has been demonstrated by the relatively high barrier to rotation (AG* = 14.2 kcal mol-1 at ca. 30 "C) about the P-N bonds, measured by l H and 1 3 C n.m.r. The formation of phosphazenes by the reactions of amides with phosphines and carbon tetrachloride in the presence of a base continues to be intensively studied. Recent examples of this reaction include :21 R2P(X)NH2
+ Ph3P +
ccl4 +[R2P(X).NH *f'Ph3]Cl-
-1 +
Et,N.
+
CHC13
- HCI
RzP(X) * N=PPh3 R = OAlk, OPh, or Ph X = OorS
In two cases, cyclophosphazeneswere unexpectedly obtained from these reactions by elimination of triphenylphosphine oxide : R2P(O)*NH2
+ PPh3 + cch +NsP3(OR)6 +
Ph3PO
+
CHC13
+
HC1
(R = OEt or Ph)
N-Sulphonylphosphazenes are also readily obtained by this route : PhzPX
+ cc14 + RSOz*NHz + EtsN +Ph2XP=N*SOzR + CHC13 + Et3NH C1X = Ph; R = Me, F, NAlk2, or OAlk (ref. 22) X = Ph, NMe2, or NCBHIO; R = Ph and substituted Ph (ref. 23)
The influence of the amide, the solvent, the temperature, the concentration of phosphine, and an excess of phosphine, on the course of this reaction have been examined2*by g.1.c. determination of the amount of chloroform produced. The mechanism has also been discussed by reference to these effects. New methods for the synthesis of phosphazenes include the reactions of phosphoranes with N-lithiated imides :25 RPF4
+ LiN =C(CF3)z
__+
+
RPF3 - N =C(CF3)2 RPF2 =N C(CF3)2 N =C(CF3)2 (R = Et or Ph) *
the reaction of guanidylphosphonium salts with sodamide :zs [PhsG.N=C(NH2)NR1R2]CI-
(R1andR2 20
21 22 23 24
25 26
NaNHz. - HC1
Ph3P=N * C(NH)NR1R2
= H or alkyl)
M. G. Thomas, R. W. Kopp, C. W. Schultz, and R. W. Parry, J . Amer. Chem. SOC., 1974,96, 2646. R.Appel and H. Einig, Chem. Ber., 1975, 108, 914. R. Appel and H. Einig, 2. Naturforsch., 1975, 30b, 134. I. N. Zhmurova and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.),1974, 44, 79. R. Appel and K. Warning, Chem. Ber., 1975,108, 606. J. A. Gibson and R. Schmutzler, Z . Naturforsch., 1974, 29b, 441. A. Heesing and G . Imsieke, Chern. Ber., 1974, 107, 1536. -
193
Phosphazenes
and the reaction of triphenylphosphine with anthranil~,~' e.g. the reaction of (10) with Ph3P to give (11). The fact that (11) is stable in refluxing toluene, and yet
e.g.
a 0 + Ph,P
- aCHO \
N=PPh,
contains the elements of triphenylphosphine oxide, is believed to be due to resonance stabilization between (12) and (13).
It has been found2* that the tris(trifluoromethy1thio)amine (CF3S),N oxidizes triphenylphosphine to a phosphazene: (CF3S)3N
+ Ph3P +CFsS*N=PPh3 +
CF3S.SCF3,
but that the phosphazene obtained from a closely related reaction is unstable, and can be best identified as an imine:29 (PhS)3N
r.t.
+ R3P +[R3P=N*SPh] + PhS.SPh JMHO
ArCH=N.SPh
+ R3PO
The phosphorane (14) eliminates trimethylsilyl fluoride on heating,30but forms a cyclodiphosphazane (15), rather than a monophosphazene. Although (Et zNCl2-
F (Me,Si),N
-Me,SiF (R =
CF,)*
R
27 28
29
30
Y . Nomura, Y . Kikuchi, and Y . Takenchi, Chem. Letters, 1974, 575. A. Haas, J. Helmbrecht, and E. Wittke, Z. anorg. Chem., 1974,406, 185. J. Almog, D. H. R. Barton, P. D. Magnus, and R. K. Norris, J.C.S. Perkin I , 1974, 853. J. A. Gibson and G.-V. Roschenthaler, J.C.S. Chem. Comm., 1974, 694.
194
Organophosphorus Chemistry
PNMe), also exists as a dimer (cyclodiphosphazane), the N-ethyl analogue undergoes tetramerization at ca. 20 "C to produce (16).31 EtNCI, + 2Et2N.PCI,
Et,N*PC14 + Et2NCbP=NEt
NEt,
3 Properties of Acyclic Phosphazenes Ha1ogenoderivatives.-The oligomeric phosphazenes CI ,P(O)(N=PC1JnC1 (n = 1, 2, or 3) (see ref. 1) are solvolysed by anhydrous formic acid:32 ChP(O)(N=PC12)nCl
+ ~HCOZH+C12P(O)~H.P(O)Cl]nCl + nCO + nHCl
The resulting acid chlorides have been ammonolysed to give the amides (H,N),P(O)[NH.P(O)(NH&NH,, the hydrolyses of which have been followed by paper and by gel chromatographies. The mercury(i1) derivative Hg(NSOF), is a versatile reagent for the preparation of otherwise inaccessible imidosulphur oxide difluoride derivatives:33 Hg(NSOF2)
+ 2Cl*SO2*N=PC13+2FzS(O)=N.SO2.N=PCls +
HgCla
ISOF.
F2S(O)=N~SO2*N=S(O)F2
+ FzPCls
There appears to be no evidence for initial reaction at the =PCI, group. This group is, however, readily alc~holized,~~ and in some cases the products undergo a rearrangement in methylene chloride solution. The rearrangement product can be cyclized to a six-membered heterocycle (1 7) on further reaction with heptamethyldisilazane. Brief details35of the reactions of N-sulphonyl-phosphazenesArSO, *N=PCI,X (X = C1 or Ph) with NaOOBut have been published. The diperoxides ArSO,.N= P(OOBut),Ph were isolable, but no triperoxides &SO, - N=P(OOBut), were obtained. 31 A. M. Pinchuk and V. A. Kovenya, J . Gen. Chem. (U.S.S.R.), 1974, 44, 673. s2 L. Riesel and R. Somieski, 2. anorg. Chem., 1975, 412, 246. 33 C. Jaeckh and W. Sundermeyer, Angew. Chem. Internat. Edn., 1974, 13, 401. 34
35
G. Schoning, U. Klingebiel, and 0. Glemser, Chem. Ber., 1974, 107, 3756. A. G. Babyak and T. I. Yurzhenko, J. Gen. Chem. (U.S.S.R.), 1974, 44, 453.
-
Phosphazenes + 2ROH
SO,(N=PC&),
195
=
I//
R
+ 2HC1 (R = alkyl)
SO,(N=-PCI,OR),
Me or Et), CH,Cl, solution
0
Y-p, ,NMe
02s\ N-P
(17)
Interest in the chemistry of N- and P-chloroalkylphosphazenes has been ~ustained.~~ e.g. (C13C)2ClP=NH R X -+ HX + (C13C)zClP=NR
+
(R = halogenosilyl, halogenogermyl, or acyl group)
The N-acyl compounds are thermally unstable and have not been obtained in a pure state: (C13C)zClP=NC(O)Ar
(CbC)2P(O)Cl
+ ArCN
but the silyl- and germyl-derivatives are readily isolable, and their i.r. spectra have been discussed in some detail. The N-trichloromethyl derivative C13C.N=PC13, obtained by the reaction:
+ 2PC15+KC1
KSCN
+
P(S)C13
+
C13C*N=PC13
undergoes preferential aminolysis by arenesulphonamidesat the carbon atom :37 CbC-N=PC13
+ ArSOzNHz +ArSOzN=CCl*N=PC13 + 2HC1 ArSOzCl
+ [ChP=N.CN]
1 3C3N3(N =Pc13)3
The product, a thermally unstable iminophosphazene, rapidly forms an interesting C-tris(trichlorophosphazeny1)triazene. Reactions with DMF and with FriedelCrafts reagents have also been explored, with the following results: ClsC*N=PC13 C13C.N-PC13 313
37
+
+
Me2N.CHO +COz
AICl,
GHs +HC1
+
+
Me2N-CHClz H,O
PhCClz*N=PC13.AlC13+PhCN
8. S. Kozlov, S. N. Gaidamaka, and L. I. Bobkova, J. Gen. Chem. (U.S.S.R.), 1974,44, 1034. V. Ya. Semenii, A. P. Boiko, G. F. Solodushchenko, N. A. Kirsanova, and V. P. Kukhar', J. Gen. Chem. (U.S.S.R.), 1974,44, 1229.
196
0rganophosphorus Chemistry
N-Chloroalkylphosphazenesalso react readily with DMSO :38 RClzC*N=PCL
+
Me2SO L_, [RClC=N-P(O)C12]
+
MeSCHzCl
+
HCl
R.CO *NH P(O)Cl2 *
The vibrational spectra of the cyclodiphosphazanes (X,PNMe), (X = C1 or F) and phosphazenes R,P=NMe (R = OMe or NMe,) have been with particular reference to P-N stretching frequencies (see also ref. 7). The i.r. spectra of C13P=N * S02CI, [H2NPh2P=N=P(NH2)Ph2]+C1-, and [C13P=N. C1,P=N - PC13]+ [PCI,]- have been As a result of this work, the vibrational assignments for [Cl,P=N=PCl,]+ [PCI,]- have been revised. N.q.r. spectroscopy continues to give useful information on the chlorophosphazenes, and the temperature dependence of the 35Clspectrum of Cl,C-CO.N=PCl3 has been reported in detai1.41s42 Alkyl and Aryl Derivatives.-The chemistry of the phosph(II1)azenes is currently a fruitful area for research (see also refs. 14-16). Addition of diazomethane to (Me,Si),N-P=N.SiMe, in the formation of the ring compound (18). Where %N\p/NR
R2N.P=-NR
CH Na =
$*
/\
R,N-P(CX,)=NR
__f
X,C-CH, (18)
further oxidation cannot occur, as in R2N- P(=NR),, diazomethane adds a methylene group across a phosphazene bond to give (19). It is also worth noting that the
(R = Me,Si) (19) crystal of (Me,Si),N.P(=N.SiMe,), shows a planar distribution of bonds about phosphorus (see Section 7). When boron trihalides are added to (Me,Si),N * P-N SiMe,, the new four-membered-ring compound (20) is obtained.46 X
-
&N-P=NR
+ BX,
-
(R = Me,Si; X = C1 or Br)
B
\NR
RN’
\P/ X (20)
38
39 4O
4l 42 43 44
45
V. P. Kukhar’ and A. P. Boiko, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2072. P. Haasemann and J. Goubeau, Z . anorg. Chem., 1974,408,293. R. M. Clipsham, J. D. Pulfer, and M. A. Whitehead, Phosphorus, 1974, 3, 235. V. A. Mokeeva, I. V. Izmest’ev, I. A. Kyuntsel, and G. B. Soifer, Pis’ma Zhur. Eksp. Teor. Fiz., 1974, 19, 580 (Chem. Abs., 1974, 81, 43 728h). V. A. Mokeeva, 1. V. Izmest’ev, I. A. Kyuntsel, and G. B. Soifer, Fiz. Tverd. Tela, 1974,16, 3649 (Chern. A h . , 1975, 82, 117 999s). E. Niecke and W. Flick, Angew. Chem. Internat. Edn., 1975, 14, 363. S. Pohl, E. Niecke, and B. Krebs, Angew. Chem. Internat. Edn., 1975, 14, 261. E. Niecke and W. Bitter, Angew. Chem. Internat. Edn., 1975, 14, 56.
Phosphazenes
197
There are four different compounds, all containing a P-0 bond, that could result from the thermal isomerization of (EtO),P=N-P(S)(OEt),, but only two of these are actually formed:46 (Et0)3P =N.P(S)(OEt)z
+(EtO)zP(O) - N=P(SEt)(OEt)2 (Et0)3P = N * P(O)(SEt)(OEt)z
The two isomers obtained were sufficiently stable to be obtained independently by the azide route: e.g. (Et0)3P
+
(Et0)2(EtS)P(O)N3+(Et0)3P=N .P(O)(SEt)(OEt)2
+ N2
The alkoxyphosphazene (EtO)3P=N. Ph reacts with aldehydes as expected to give irnine~,~? but no reaction occurred with acetone:
+
ArylCHO
(Et0)3P=NPh
-+
(Et0)3PO
+
ArylCH=NPh
The P-N bond in the same compound is also cleaved by reactions with nitrosyl chloride :4 (R0)3P=NPh
+
NOCl+ Phkz C1(R = Et or Bun)
+ (R0)3PO
Numerous examplesof the reactions of diphosphazenylalkaneshave been reported. via a Wittig-type reaction : With diketones, cyclic imines are
Ph,P=N(CH,),
N-PPh,
+ R1-CO[CR2R3J,CO*R4
(e.g. R' = Me; R2 = R3 = H;
Rf
-
R'
,N=C
\
(CH,), N=C
= Me,
R4
+ 2Ph,PO When n = 0, and rn = 1, substituted pyrazoles were obtained, depending on the nature of the R2substituent. Phosphazenesreact with diphenylketen to give thermally stable ketenimines9O Ph3P =N - CR1R2R3
+
PhzC =C =0 +PhzC =C =N CR1R2R3
+ Ph3PO
(R1,R2, and R3 included H, Me, and Ph) and reactions with sulphenes (generated from MeS0,Cl and Et,N) give a complex mixture of products:61 Ph3P=NPh
Ph3P =N .SO2 - NPh SOzMe 46
47 48 49
50
51
+
+ 2MeSOzCl +
2Et3N
Ph3P =C(S02Me)S02NHPh
+ (traces) Ph3*CH2S03-
A. A. Khodak, V. A. Gilyarov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1974,44,241. V. A. Gilyarov and M. I. Kabachnik, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1973, 2374. V. A. Gilyarov and T. M. Shcherbina, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1974, 2870. R. Appel and P. Volz, Chem. Ber., 1975, 108, 623. K.-W. Lee and L. A. Singer, J. Org. Chem., 1974, 39, 3780. T.Kawashirna and N. Inamoto, BuN. Chem. SOC.Japan, 1974, 47, 2444.
198
Organophosphorus Chemistry
This, and related reactions, may proceed by nucleophilic attack of the nitrogen atom on the sulphur atom in CH,=SO,, to give an intermediate (21), followed by methylenephosphorane formation. N-iminophosphazenes react with certain acetylenes to give phosphadiazidines (22).62 Ph,P+-NAr
I
CH,- SO, (21)
RIRT=N
*
+ Me0,C - C E C - C0,Me --+
N=PPh,
MeO$
C0,Me (22)
The Lewis-base properties of triphenylphosphazenes have been studied. Diphosphazenylalkanes act as bidentate ligands towards metal(@ halides, forming complexes (Ph3P=N.CHz.CH2-N=PPh3)MX2 (M = Co, Hg, Ni, or Cd; X = C1, Br, or I) in which a metal-nitrogen bond is formed.63The magnetic moments and electronic spectra of some of these complexes have been measured. The phosphazenes R1,R2P=NAr also act as nitrogen donors to (NC),C=C(CN),, an interaction by observation of the formation of a radical anion of the which was latter molecule. A number of reactions at the N-H bond in Ph3P=NH and its P-alkyl analogues have been followed. With potassamide the products are quite sensitive to the nature of the P-substituent Me3P=NH
e.g.
Et3P=NH
[ KNHcNHI
KNH,-NH,
Me3P=NK
]
EtaP.NH.PEt2 N
K2
N
KNHa-NH,
In these examples, increasing electronegativity of the P-substituents facilitates cleavage of the P-C bonds. Relatively few N-phosphinophosphazenes are known, a more convenient and the transamination of Ph,P-NMe, by Ph,P=NH route to Ph3P=N-PPh2 than previously used: Ph3P=NH 52
53 54
55 56
+
PhzP-NMea +Ph3P=N
+
MezNH
I. Shahak and Y.Sasson, Israel J. Chem., 1973, 11, 729. R. Appel and P. Volz. 2. anorg. Chem., 1975, 413, 45. V. V. Pen'kovskii, Yu. P. Egorov, R. I. Yurchenko, and A. P. Mzrtynyuk, J . Gen. Chern. (U.S.S.R.), 1973, 43, 2618. B. Ross and K.-P. Reetz, Chem. Ber., 1974, 107, 2720. I. N. Zhmurova, A. P. Martynyuk, A. S. Stepanek, V. A. Zasorina, and V. P. Kukhar', J. Gen. Chem. (U.S.S.R.), 1974, 44, 76.
Phosphazenes
199
The tervalent phosphorus atom in this compound undergoes a ready reaction with aryl azides to give diphosphazenes Ph3P=N-Ph2P=N.Ar, and pKa data for these derivatives have been obtained. Addition of Ph,P=NH to isocyanates gives phosphazenyl-ureas
Ph,P=NH
YP(O)(NCO)2 RNCO
[PhsP=N*CO*NH]2P(O)Y (Y = Alk or Ar)
Ph,P==NH
RNH.CO*N=PPha
[R = Ar, ChP(O), or MesSi] Ph,P-NH
Si(NCO)4 -+Si(NC0)4-n(NH. CO *N=PPh& (n = 1-3)
Hydrogen-chloride-inducedcleavage of the P=N bond in nitro- and cyanosubstituted arylphosphazenes results in aromatic m i n e formation :68 Ph3P =N - Ar
+ 2HCl+
Ph3PC12
+ ArNH2
N-Silyl-substituted phosphazenes have been subjected to reactions with a wide range of acid halides. Thus, the diphosphazenes R2P(=N SiMe,)(CH&P(=N*SiMe,)R, are converted into fluorophosphoranes on reaction with HF: 6 8 R2P( =N - SiMes)(CH2),P( =N .SiMes)Rz
+ HF --M@F. NH,F
____+
R~F~P(CH~)SPF~RZ
(R = Me,n = 3 ; R = Ph,n = 1 or2)
Reactions of PF,,Et 20or PhPFl with silylphosphazenes give fluorophosphonium salts : 0 R1R22P=N -%Me3 + 2PF5,EtzO +[R1R22P=N .PFs]+ ~ F s ] -+ MesSiF (R1 and R2 = Me and/or Ph) With a 1 : 1 molar ratio of reactants the products are [(R1R22P=N)2PFJ+[PF6]-, and phosphonium salts with different phosphazenyl substituents were easily synthesized: e.g.
PhsP=N.SiMes
+ [MesP=N*PFs]+ fpFs]-
1
[(PhsP=N)(Me3P=N)PF2]+ [PFs]-
+ MesSiF
Even triphosphazenyl derivatives are formed under more forcing conditions (refluxing acetonitrile): [(MesP=N)2PF2]+ [pF6]-
+
MesP=N-SiMes -+ [(Me3P=N)sPF]+ [pFs]-
+
MesSiF
The 13C, 18F, and 31Pn.m.r. spectra of these derivatives have been reported and discussed. A somewhat different route 61 to bis(phosphazeny1)phosphonium salts A. S. Stepanek, V. V. Doroshenko,V. A. Zasorina, L. M. Tochilkina, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.),1974,44,2092. 5 8 B.A.S.F. A.-G., Fr. Demande 2 214 682 (Chem. A h . , 1975,82, 139 791v). 59 R. Appel and I. Ruppert, Chem. Ber., 1975,108,919. eo R. Appel and I. Ruppert, Chern. Ber., 1975,108, 589. 61 W.Wolfsberger, J. Organometallic Chem., 1975,86, C3.
57
200
Organophosphorus Chemistry
-
involves thermolysis of the salts [R3P=N.PR2.PR2]+C1-: R3P = N - SiMes
+
PhzPCl
- Me,SiCI
[R3P=N * PPh2 - PPhz]+ C1-
1
heat
[(&P=N)aPPh2]+ C1-
+ PhzPCl + PhzP.PFh2
(R = Et or Ph) The ring compound S4NI also effects the cleavage of the Si-N bond in silylphosphazenes,62but with the formation of a cyclotrithiazene ring system (23). An RIGP=N-SiMe,
+ S,N,
R'GP=NS
,N=S
\
\\
//
N-S
(R'and R2 = Me and/or Ph)
N + Me,Si.N-S=N.SiMe,
+ S,
(23)
analogous reaction is observed with the diphosphazene Me,P(=N - SiMe3)(CH2),P(=N - SiMe,)Me,, and exchange reactions of the trithiazyl-ring with silyl groups have been followed. Several interesting exchange reactions involving silyl and germyl groups have e.g. as shown in reactions (1)-(3) been carried out on diphospha~enylsilanes,~~
+ RSiC1,
(Me,P=N),SiMe,
(R = Me,Et,orCl)
-
Me,P=N
- SiRC1,
+
(24)
(Et3P =N)zSiMez
+ RSiC12 +Et3P = N .SiRClz +
MeaSiClz
(2)
(R = Me, Et, or C1)
(R,P=N),SiMe,
+ M%GeX,
(R = Me; X = C1, Br, or I; R = Et; X = B r o r I)
(25)
The 31P and 13C n.m.r. spectra of a series of N-silylphosphazenes R1R2R3P= , ~ ~ the 13C N-SiMe, (R1, R2, and R3 = alkyl and/or Ph) have been d e s ~ r i b e d and n.m.r. spectra of Ph3P=N .Ph and Ph3P=N -N=CH2 compared with related data for other ylidic Studies of the auxochromic action of phosphazenyl groups continue, and recently 62
63 64 65
I. Ruppert, V. Bastian, and R. Appel, Chem. Ber., 1974, 107, 3426. W. Wolfsberger, J. Organometallic Chem., 1975, 88, 133. W. Buchner and W. Wolfsberger, Z . Narurforsch., 1974, 29b, 328. T. A. Albright, W. J. Freeman, and E. E. Schweizer, J . Amer. Chem. SOC.,1975,97, 940.
201
Phosphuzenes
the effect of exchanging dimethylamino-groups for phenyl groups in the Phn(Me,N),_,P=N grouping was found to be relatively The sums of the Hammett constants of substituents on the aryl groups in monophosphazenes ArAr’Ar”P=N .Ar”’ are linearly related to their pKa values.67These constants are also correlated with the heats of formation of the complexes CCl,.CO,H,Ph,P= N.C6H4-p-X(X = H, F, C1, Br, I, Me, or NO,), obtained by calorimetric titration in benzene.s8Several rather exotic phosphazenes of the type (ArCO,),P=N.CO .Ar and R(ArC02),P=N * C(=NPh)CCI, have been synthesized because of their potential herbicidal 6 B s 7 0 and fungicidal71 activities. 4 Synthesis of Cyclic Phosphazenes New routes to halogenocyclophosphazenes continue to be established. A mixture of oligomeric fluorocyclophosphazenes (NPF& (n = 3-9) is obtained 72 in 60% yield, together with PF, and PF5, when NF3, P4S3,and PaSloare heated together in a nickel tube at 180-21 5 “C. A similar homologous series of fluorocyclophosphazenes can be obtained by heating the cyclodiphosphazane (MeNPF3)2at 200 “C for several hours. Similarly, chloro- and chloro(pheny1)-cyclophosphazenes were obtained 73 by heating (MeNPCl,), and (MeNPCI,Ph),, respectively. They were characterized by 31Pn.m.r. and mass spectra, and by molecular weight determinations. Improvements in the synthesis74 and purification 75 of oligomeric chlorocyclophosphazenes (NPCl,), have been de~cribed.~~N-labelled N,P,C16 has been prepared 7 6 by the 15NH4C1-PCI,-pyridine reaction in the absence of solvent. The injection of ammonia into a PBr3-Br, mixture constitutes an improved route to N3P3Br6for semiconductor applications. An interesting route 7 8 to a trihydrocyclophosphazene(26) involving oxidation of tervalent phosphorus is provided by the reaction:
(Me,N),PCI + 3NH3
-
,NM% H\p/N\ Me,N’II N\p#N
\PLH
+ 3McjfiH2 Cl-
/A\
H
66
67 68
69
70 71 79
73
74 75 76 77
7*
NMe,
(26) R. I. Yurchenko and I. N. Zhmurova, J. Gen. Chem. (U.S.S.R.),1973, 43, 2614. I. N. Zhmurova, V. G. Yurchenko, V. P. Kukhar’, and L. A. Zolotareva, J. Gen. Chem. (U.S.S.R.), 1974, 44, 70. N. A. Ivanova, V. A. Kogan, I. P. Gol’dshtein, E. N. Guryanova, 0. A. Osipov, N. N. Kharabaev, A. S. Egorov, and K. A. Kocheshkov, Dolclady Akad. Nauk. S.S.S.R.,Ser. khim., 1974, 217, 1341. K. A. Abromova, V. P. Rudavskii, and M. N. Kucherova, Fiziol. Aktio. Veshchestua., 1973,5, 20 (Chem. Abs., 1974, 81, 100 557c). M. N. Kucherova, P. S. Makevetskii, V. P. Rudavskii, and D. F. Shiranov, Nauk. Pr. Ukr. Sil’s’Kogospod.Akad., 1973, 96, 148 (Chem. Abs., 1975, 82, 39 370p). T. I. Cherepenko, G. A. Golik, V. A. Shokol, V. M. Lopatin, and L. P. Rudenko, Fiziol.Aktiu. Veshchestua, 1973, 5 , 6 (Chem. A h . , 1974, 81, 58 682n). A. Tasaka and 0. Glemser, Z. anorg. Chem., 1974, 409, 163. H.-G. Horn,2. anorg. Chem., 1974, 406, 199. C. R. Bergeron and J. T. Kao, Fr. Demande 2 187 689 (Chem. Abs., 1974, 81, 51 816a). A. F. Halasa and D. L. Snyder, U.S.P. 3 829 554 (Chem. Abs., 1974, 81, 13 798c). Yu. N. Pashina and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 433. G. Wunsch and V. Kiener, Ger. Offen. 2 302 512 (Chem. Abs., 1974, 81, 128 7580. A. Schmidpeter and H. Rossknecht, Chem. Ber., 1974, 107, 3146.
0rganophosphorus Chemistry
202
Although (26) is thermally unstable at ambient temperatures, it was possible to obtain n.m.r. and mass spectroscopic information. Phosphazenylphosphonium salts are converted into spirocycliccompounds, e.g. (27), by reaction with phosphorus(1n)
tri~hloride.'~ Subsequent amination yields (28). The formation of (27), or a monocyclic phosphazene, is apparently determined by the ease of oxidation at tervalent phosphorus in a monocyclic intermediate. A similar reaction with MePCl, results in the formation of monocycle (29).
/ \C1
Me
(29)
The heterocycle (30) can be obtained by the thermolysis reaction shown.80This result may be contrasted with the non-cyclization of CI,P(O)(N=PCl,) .NH * SiMe, (ref. 1).
Me,SiCl
Ring closure of an acyclic phosphazene has been effected by reaction with S02(NH2)2:81 [C13P=N*C12P=N.PC13]+IpCle]-
- HCI + S02(NHz)2 + (NPClz)sNS(O)Cl
The i.r. and mass spectra of the product were closely related to that of (NPCI2)*. No further information on the four-membered cyclophosphazene ring reported last year has appeared, although a surprising result is that the reactiona2between CF3* CCI2*N=PCI3 and NHICl affords the six-membered-ring system (31). CCI,CCI - N=PCI, gave a four-membered ring under similar conditions. Compound 79 80
81 82
A. Schmidpeter and H. Eiletz, Chem. Ber., 1975, 108, 1454. H. W. Roesky and W. Grosse-Bowing, 2. anorg. Chem., 1974,406, 260. C. Voswijk and J. C. van de Grampel, Rec. Trav. chim., 1974, 93, 120. V. P. Kukhar' and T. N. Kasheva, J. Gen. Cliem. (U.S.S.R.), 1974, 44, 2104.
Phosphazenes
203
(31) undergoes reactions at the =PClz group with formic acid, aniline, and NaOC,H,-p-NO, to give -CIP(O)NH-, =P(NHPh),, and -P(OC6H4-p-N02)a ring substituents,respectively. The related ring systems (32) and (33) can be obtained
R XCH,CN + RCCI,.N=PCl,
XCNC%N 11 1 CIC,NgW
+ NC(X)C=C.R*N=-PCI,
(ref. 84)
(33)
by the reactions 84 It was previously considered that the phosphazenes R - C O-NH.N=PX, were formed from the reaction of acyl-hydrazineswith chlorophosphoranes, but recent work 85 shows that the five-co-ordinated phosphorus compounds (34) are in fact obtained from this reaction.
5 Properties of Cyclic Phosphazenes Halogeno-derivatives.-The l9Fand some 31Pn.m.r. spectra of a series of fluorocyclo(n = 3 or 4; X = Cl or Br) and N3P3ClzF2(NMe,),,all phosphazenes N,P,X,F,-, of which have at least two isomeric forms, have been reported.86Iterative fitting by computer enabled their spectra to be analysed, and trends in chemical shifts and coupling constants have been discussed. N5PBCllocan be fluorinated by KSOaF to give a mixture of chloride-fluorides N5P,C16-,F, (n = 1-9), but no compound containing more than one r P C l F As was found with N3P3Cl6and N4P,Cl,, 83 84
85 86
87
P. P. Kornuta and T. V. Kolodka, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2556. V. P. Kukhar’ and A. P. Boiko, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1224. A. Schmidpeter and J. Luber, Chem. Ber., 1975, 108, 820. P. Clare, D. B. Sowerby, R. K. Harris, and M. I. M. Wazeer, J.C.S. Dalton, 1975, 625. N. L. Paddock and J. Serreqi, Cunad. J. Chern., 1974, 52, 2546.
204
0rganop hosphorus Chemistry
replacement of chlorine occurs by a geminal pattern, but the complexity of the 19F n.m.r. spectra makes it difficult to establish alternative geminal pathways. Some indication of a non-specific geminal scheme came from the identification of isomers (35) and (36) (N and C1 atoms omitted), which were formed in approximately equal
quantities. The importance of n-inductive effectsin determining the relative rates of formation of mono- and di-fluoro-derivativeshas been emphasized. CNDO calculations have been performed on N2PZF4, N3P3H6,and N3P3F6,and possible reasons for the non-existence of the first two molecules discussed. Calculations of excited states of known and unknown molecules, N2P2F4,N3P3F6,N3P3H6, N4P4F8,N3P3CI2H4, N3P3CI3H3,and N3P3CI4F2,have also been carried out by the same method.89The CND0/2 method has been employedgoto show that the N4P4 ring might deviate from planarity to an increasing extent with increasing hydrogen substitution in the series N,P,F,-,H, (n = 0 , 2 , 4 , and 8). Further studies 91 of the Faraday effect on N3P3X6,N4P4X8,and N5P5X10 (X = F, C1, NMe,, or OPh) provide support for the Dewar model of n-bonding in these systems. The calculation of force constants in N3P3C&has been discussed 92 and a further reportg3made on the assignment of Raman lines in the single-crystal spectra of N3P3C16and N,P,Br,. Amino-derivatives.-The amino-derivatives N3P3C14(NH2),and N3P3(NH2)*are useful hardening agents for epoxy-resin~,~~ and the retention of ~P(NH,),],,, by soils has been Both hydrogen chloride and bromide effect deaminolysis N6 of N3P3(NMe2)6in boiling xylene to give cis-N3P3Xz(NMe,),and cis- and transN3P3X3(NMez),(X = C1 or Br), although the bromides are accompanied by a significant proportion of decomposition products. By contrast, hydrogen iodide gives adducts N3P3(NMe2),,HX(X = I or 13). The results of CND0/2 calculationson the three isomeric forms of N3P3C13(NMe2)3, of which the crystal structures are known, have been discussedg7in terms of the physical and chemical properties of these compounds. The course of the reaction between N3P3C16and diethylaminegsis closely related 88 89
91 92
93 94
95 96
97 98
D. R. Armstrong, M. C. Easdale, and P. G. Perkins, Phosphorus, 1974, 3, 251. D. R. Armstrong, M. C. Easdale, and P. G . Perkins, Phosphorus, 1974, 3, 259. J.-P. Faucher and J.-F. Labarre, Phosphorus, 1974, 3, 265. J.-P. Faucher, 0. Glemser, J.-F. Labarre, and R. A. Shaw, Compt. rend., 1974, 279, C, 441. R. E. Christopher and P. Gans, J.C.S. Dalton, 1975, 153. J. Klosowskii and E. Steger, Spectrochim. Acta, 1974, 30A, 1889. Yu. P. Belyaev, M. S. Trizno, and N. F. Nikolaev, Plast. Massy, 1974,77 (Chem. Abs., 1974,81, 153 388e). A. P. Conesa, G. Albagnac, and G . Brun, Compt. rend. Agric. Fr., 1973,59, 1457 (Chem. Abs., 1974, 81, 168 570g). S. N . Nabi, R. A. Shaw, and C. Stratton, J.C.S. Dalton, 1975, 588. J.-P. Faucher, J.-F. Labarre, and R. A. Shaw, J. Mol. Structure, 1975, 25, 109. W. Lehr and N . Rosswag, 2. anorg. Chem., 1974, 406, 221.
Phosphazenes
205
to that taken by dimethylamine. Thus both cis- and trans-isomers of N3P3C16-,(NEt2), (n = 2 , 3 , or 4) have been separated (in some cases by g.1.c.) and identified. Additionally, a geminal trisdiethylamino-derivativewas obtained, the formation of which is favoured at higher temperatures (ca. 140 “C). Nine out of a total of twelve possible substitution products were obtained. The known piperidino-derivatives N3P,C~,-,(NC6Hl0), (n = 1 4 ) react with boiling benzene in the presence of anhydrous aluminium chloride to produce phenylpiperidino-derivatives N3P3Ph,CI,-,-,(NC,Hlo),.sg Under these conditions the replacement of chlorine by phenyl groups only occurred at =PclNC6Hlo groups, and, unlike the analogous reactions with dimethylamino-derivatives,hydrocarbon formation was not observed.Dimethylaminolysis of phenylpiperidino-derivatives has been used as an aid to structural assignments. Hexamethyldisilazane, (Me3Si)2NH, undergoes only a very sluggish reaction with N3P3Cle,even in sealed-tube reactions. Interestingly, however, small yields of a geminal product were obtained :l O O N ~ P ~ C+~2(Me3Si)2NH S __+ NaP3C14(NH .SiMe3)2
+ 2MeaSiCl
In view of the absence of a monosilylamino-derivative and the formation of a geminal product, reactions with (Me,Si),NH are similar to those with ammonia and t-butylamine (the latter m i n e gives low yields of a monoamino-derivative). The product of the reaction of the stannylamino-derivative N3P3F,.N(SnMe,), with S3N2CI2is either (37) or (38).lo1 35CI n.q.r. spectroscopy shows considerable N,P,F5-N=S
(37)
,N% \
I
N,P,F,-N
F-Y, S
\
S -N
S”
//
(38)
potential for distinguishing positional isomers of aminochlorocyclophosphazenes,lOa although at present it seems difficult to distinguish geometrical isomers. A more convenient technique for distinguishing positional isomers of bisamino-derivativesof N4P4C18is 31Pn.m.r. s p e c t r o ~ c o p ysince , ~ ~ ~structures (39), (a), and (41) give AB2C,
A2B2, and AA’BB’ spectra, respectively (N, CI, and amino-groups omitted for convenience). Isomeric forms of N4P4C16(NR1R2)2 (R1 = H, R2 = But; R1 = H, 99 S. Das, R. A. Shaw, and B. C. Smith, J.C.S. Dalton, 1974, 1610. loo A. T. Fields and C. W. Allen, J. Inurg. Nuclear Chem., 1974, 36, 1929. l01 H. W. Roesky and E. Janssen, Chem. Ztg., 1974, 98, 260.
H. Dalgleish, R. Keat, A. L. Porte, D. A. Tong, M. U1-Hasan, and R. A. Shaw, J.C.S. Dalton, 1975, 309. R. Keat, S. S. Krishnamurthy, A. C. Sau, R. A. Shaw, M. N. Sudheendra Rao, A. R. Vasudeva Murthy, and M. Woods, Z . Naturforsch., 1974, 29b, 701.
lo2 W. 1°3
206
Organophosphorus Chemistry
R2 = Et; R1 = Me, R2 = Ph) were distinguished in this way. The basicities of the dimethylaminocyclophosphazenes [NP(NMe2),ln (n = 3-7) and the P-Pbonded compound [N3P3Ph(NMe2)J2have been measured O4 on samples in nitrobenzene solution. Alkoxy-and Aryloxy-derivatives.-Most of the interest in this topic during the past year has centred around the synthesis of fire retardants. For example, the n-propoxyderivatives so favoured for this purpose have been decolorized by reaction with ozone105and modified by reactions with phosphorus pentoxide.lo6The products of
benzylicl10 diols, also have fire-retardant properties. Another diol product, N,P,(OCH,C,H,-o-CH,OH),, has been used as a precursor of thermoplastic polyPreparative details for compound (42) have also been described. The i.r. and
mass spectroscopic, as well as thermogravimetric, properties of the aryloxy(X = C1, Br, or F) have been reported and disderivatives N3P3(OC6H4-p-X)6 cussed.112Epoxides undergo ring opening on reaction with NlP4Cl in the presence of lithium halides, thus providing a route to chloroalkoxy-derivatives:113 /O\
N4P4c1,iH,C-CH,
N,P,(OCH,CH,Cl),
The role of lithium halides in the catalysis of this reaction has also been discussed; lithium bromide is particularly effective in this respect, and its activity may be due to the ease with which it opens the oxiran ring. Ammonium salts of carboxylic acids are converted into nitriles by N,P,Cl,. 15N labelling of N3P,C16(see ref. 76) shows that the nitrogen atom in the CN group comes from the cyclophosphazene, rather than the NH,+ ion:11P 15N3P3Cltj 4- N&C02CsH4-p-N02 104
+OzN. CtjH4-j&15N
S. N . Nabi and R. A. Shaw, J.C.S. Dulton, 1974, 1618. C. Patel, Ger. Offen. 2 348 950 (Chem. Abs., 1975, 82, 87 609v).
lo5V. 106 B.
R. Franko-Filipasic and J. F. Start, U.S.P. 3 836 599 (Chem. Abs., 1975, 82, 74 315w). G. Wunsch, V. Kiener, F. Fuchs, W. Himmele, and W. Fliege, Ger. Offen. 2 252 485 (Chem. Abs., 1974, 81, 122 683t). 108 R. Wolf, Swiss P. 548 420 (Chem. Abs., 1974, 81, 37 241c). 109 H. Saito and M. Kajiwara, Jap. P. 74 12 570 (Chern. Abs., 1974, 81, 154 781q). 110 H. Rose, Ger. Offen. 2 313 530, 2 313 531 (Chem. Abs., 1975, 82,4319~1,4 3 2 0 ~ ) . 111 M. Kajiwara and H. Saito, J. Inorg. Nuclear Chem., 1975, 37, 29. 112 R. L. Dieck and M. A. Selvoski, Inorg. Nuclear Chem. Letters, 1975, 11, 313. 113 D. F. Lawson, J. Org. Chem., 1974, 39, 3357. 114 Yu. N. Pashina and B. I. Stepanov, J . Gen. Chem. (U.S.S.R.), 1974, 44, 440. 107
Phosphazenes
207
Alkanethiol Derivatives.-The reactions of N3P3Clswith sodium methanethiolate have been studied for the first time:116 NaP3Cle
+ nNaSMe -+
N3P3C16-n(SMe)n + nNaCl
As with NaSEt, geminal products were obtained when n = 2,3, and 4, but no monoderivative (n = 1) could be obtained by this route. This latter derivative was obtained by chlorination of the derivatives N3P3Cl,-,(SMe)n (n = 2,4, or 6) in the presence of U.V. light. The types of reactions occurring under these conditions are: -HCI
+ Cl2 --+ =P(SMe)(SCCls) -ClSCCI, =P(SMe)(SCCL) + Cl2 GPClSMe etc. =P(SMe)z
____+
Salient features of the i.r. and ,lP n.m.r. spectra of these derivatives have been described. Alkyl and Aryl Derivatives.-The formation of the salts N,P,Me,,HCI, NZ4Mq,2HC104, N6P6Mel,,,H2CuC14,H20,and complexes N4P4Me8,2HgCl8,N4P4Me*,4AgNO,, N4P,Me,,HCl,CuC12, and the quaternary salts [NPMeJn,RI (n = 3-5, R = Me or Et) has been discussed11ein terms of the participation of phosphorus d-orbitals in bonding. The U.V. spectra of the methylcyclophosphazenesindicate that there is a relatively large disparity in phosphorus and nitrogen orbital energies, so that methylcyclophosphazenes make no significant use of antibonding orbitals in bonding with transition metals. The octamethyl derivative can be lithiated at the methyl groups on different phosphorus atoms by methyl-lithium and subsequently converted into mixed alkyl or trimethylsilylmethyl derivatives:l17 N4P4Me, + MeLi + [N4P4Me4(CH,)4]4'
N4P4Me4(CH,R),
N4P4Me;Et4
(R = GeMe, or SMeJ
It is interesting that ring cleavage does not occur, as with reactions involving chlorocyclophosphazenes. This does occur in the reaction of N4P4Me,I with KOBut, but is not apparent in reactions of N,P,Me,I with NaN(SiMe,), (Scheme 3), where a novel phosphorin structure is obtained. N.m.r. data and reactions with hydrogen iodide and with water serve to confirm these structures, and analogous results may be obtained with N4P4Me,I. Mass spectral data for the arylfluorocyclophosphazenesN,P,F,Ar,-, (n = 2,4, 115 116
l17 118
B. Thomas, H. Schadow, and H. Scheler, Z. Chem., 1975,15,26. H. T. Searle, J. Dyson, T. N. Ranganathan, and N. L. Paddock, J.C.S. Dalton, 1975, 203. H. P. Calhoun, R. H. Lindstrom, R. T. Oakley, N. L. Paddock, and S. M. Todd, J.C.S. Chem. Comm., 1975, 343. H. P. Calhoun, R. T. Oakley, and N. L. Paddock, J.C.S. Chem. Cornrn., 1975,454.
208
Organophosphorus Chemistry
Reagents : i, NaN(SiMe3)z ; ii, HI : iii, HzO
Scheme 3
or 5 ; Ar = C6HS,C6DS,or C6H,-p-NMe2) have been discussed at length.l19 The phosphorus 2p-binding energies determined by ESCA methods for N3P3C16, geminal N3P3F3Ph3,and geminal N3P3F2Ph4have been compared12*with similar data for other phosphorus compounds. 6 Polymeric Phosphazenes Only two very limited, and difficultly accessible, reviews121,122 of this rapidly expanding topic have appeared. The polymerization of N3P,C16is catalysed by water and inhibited by the presence of phosphorus p e n t a ~ h l o r i d e ,although ~~~ another report 124 indicates that the proportion of linear polymers (NPC12)nis increased with high PCl, :NH4Cl mole ratios. The cationic polymerization of cyclic ethers such as THF is catalysed by polychlorocyclophosphazenes.125 A large number of reports of the preparation of aryloxyphosphazene polymers of good thermal stability have been p ~ b l i s h e d . ~Many ~ ~ - new ~ ~ ~poly(fluoroa1koxy)119 C.
W. Allen and P. L. Toch, J.C.S. Dalton, 1974, 1685. B. J. Lindberg and J. Hedman, Chem. Scripta, 1975, 7 , 155. 1 2 1 G. Schroderheim, Plustuuerlden, 1974, 12, 40 (Chem. Abs., 1975, 82, 112 904x). lZ2 B. Laszkiewicz, H. Struszczyk, and J. Dutkiewicz, Polimery (Warsaw), 1974, 19, 116 (Chem. Abs., 1974, 81, 170 313n). 123 H. R. Allcock, J. E. Gardner, and K. M. Smeltz, Macromolecules, 1975, 8, 36 (Chem. Abs., 1975, 82, 112 332j). F. Yamada, I. Horii, T. Yasui, and I. Shinohara, Nippon Kuguku Kaishi, 1974, 2191 (Chem. Abs., 1975, 82, 58 201a). lZ51. Shinohara and F. Yamada. Jap. P. 73 93 697 (Chem. Abs., 1975, 81, 38 139n). 126 H. R. Allcock, G. Y. Moore, and W. J. Cook,Macromolecules, 1974,7,571 (Chem. Abs., 1975, 82,473811). 127 K. A. Reynard and S. H. Rose, U.S.P. 3 853 794 (Chem. Abs., 1975, 82, 98 888n). 128 S. H. Rose and K. A. Reynard, U.S.P. 3 856 713 (Chem. Abs., 1975,82,99 703j). 129 R. E. Singler, G. L. Hagnauer, N. S. Schneider, B. R. Laliberte, and R. E. Sacher, J. Polymer Sci.,Polymer Chem. Edn., 1974, 12, 433 (Chem. Abs., 1974, 81, 91 981g). 130 V. V. Korshak, V. V. Kireev, and M. A. Eryan, U.S.S.R.P. 438 669 (Chem. Abs., 1975, 82, 73 837f). 131 K. Doi, H. Kawamura, and S. Ikeno, Jap. P. 74 04 079 (Chem. Abs., 1974, 81, 136 746c). 132 H. Kawamura and S . Ikeno, Jap. P. 73 42 240 (Chem. Abs., 1974, 81, 50 305w). 133 H. Kawamura, T. Kotoguma, and M. Ohta, Jap. P. 73 30 160 (Chem. Abs., 1974,81,38 324u). 134 H. Kawamura, C. Maiguma, and M. Ohta, Jap. P. 73 32 800 (Chem. Abs., 1974,81,78 666p). 13, M. Kajiwara, Angew. Mukromol. Chem., 1974, 37, 141 (Chem. Abs., 1974, 81, 169 923m). 136 K. Doi, H. Kawamura, and S. Ikeno, Jap. P. 74 04 080 (Chem. Abs., 1974, 81, 154 048f). 120
209
Phosphazenes
phosphazenes are high-quality e l a s t o m e r ~ , ~whilst ~ ~ - ~other ~ ~ polyalkoxyphosphazenes have been synthesized with a view to improving the flame resistance of fabrics such as r a ~ o n . l ~O ~Poly(amin0)-l~ l6l,152 and poly(pheny1)-phosphazenes163 have attracted little interest. The turbidimetric determination of chlorine in phosphazene polymers has been described.lS4
7 Molecular Structures of Phosphazenes Determined by X-Ray DiffractionMethods Compound (Me3Si)zN * P( =N - SiMes)~
Comments
Planar distribution of bonds about phosphorus; P=N 1.503 A; P-N 1.646 A; LP=N-Si 148.5' [Ph3P=N=PPhs]+ [v(CO)s]First example of linear P-N-P skeleton in this type of cation. P-N 1.539(2) A is shorter than in this cation with a bent P-N-P skeleton (see below) vh3P=N:PPh3]+ Fe(C0)4C3H7]- P-N 1.57, 1.58(1) A; LPNP 145.9(8)". Conformations of Ph3P groups discussed
Re$
44 155
I56
S. H. Rose and K. A. Reynard, Polymer Preprints Amer. Chem. Soc., Dio. Polymer Chem., 1972,13, 778 (Chem. Abs., 1974,81, 38 611k). 138 K. A. Reynard, A. H. Gerber, R. W. Sicka, J. C. Vicic, and S. H. Rose, U.S.N.T.I.S. AD. Rep. 1974, No. 781 578/OGA (Chem. Abs., 1975,82, 59 404f). 139 G. S. Kyker and T. A. Antkowiak, Rubber Chem. Technol., 1974,47,32 (Chem. Abs., 1974,81, 122 227x). l 4 0 G . S. Kyker, J. A. Beckman, A. F. Halasa, and J. E. Hall, U.S.P. 3 843 596 (Chem. Abs., 1975, 82, 76 5778). 1 4 1 V. Prons, M. P. Grinblat, and A. L. Klebanskii, Vysokornol. Soedineniya, 1974, 16, A , 1620 (Chem. Abs., 1975, 82, 31 563h). 1 4 2 W. B. Tuemmler, J. F. Start, and E. F. Orwoll, Ger. Offen. 2 404 203 (Chem. Abs., 1974, 81, 171 2932). 143 H. Pohleman, R. Wurmb, W. Schwarz, G. Wunsch, V. Kiener, A. Zeidler, and B. Scharf, Ger. Offen. 2 245 079 (Chem. Abs., 1974, 81, 38 876a). 144 H. Tsuchida, Jap. P. 73 38 687 (Chem. Abs., 1974, 81, 64 307k). 145 E. Kobayashi, Jap. P. 74 39 700 (Chem. Abs., 1975, 82,44 345p). 146 A. G. Grozdov, V. V. Kireev, V. V. Korshak, G. M. Ryabokon, and V. G. Sartaniya, Plast. Mussy, 1974, 13 (Chem. Abs., 1974, 81, 78 282k). 14' V. G. Sartaniya, V. V. Kireev, and V. V. Korshak, Trudy Moskov. Khim.-Tekhnol. Znst., 1973, 74, 103 (Chem. Abs., 1975, 82, 17 205m). 14*W. B. Tuemmler, J. F.Start, and E. F. Orwoll, Fr. Demande 2 215 446 (Chem. Abs., 1975,82, 74 398a). 149 G. S. Kolesnikov, V. V. Kireev, I. M. Raigorodskii, K. A. Andrianov, L. I. Makarova, and V. A. Dmitriev, U.S.S.R.P. 414 277 (Chem. Abs., 1974, 81, 136 745b). 150 G. S. Gol'din, S. G. Fedorov, G. S. Nikitina, and S. F. Zapuskalova, U.S.S.R.P. 446 525 (Chem. A h . , 1975, 82, 112 493). G. F. Telegin, V. V. Kireev, and V. V. Korshak, Vysokomol. Soedineniya, 1974, 16, B, 75 (Chem. A h . , 1974, 81, 92 311a). 152 M. Fukuhara and S. Ozawa, Jap. P. 74 102 998 (Chem. Abs., 1975,82, 100 022v). lS3 V. M. Bykov, V. V. Kireev, V. P. Popilin, V. G. Sartiniya, and 1. B. Telkova, Trudy Moskov. Khim.-Tekhnol. Inst., 1973,74, 100 (Chem. Abs., 1975, 82, 17 148v). 154 J. Z. Falcon, J. L. Love, L. J. Gaeta, and A. G. Altenau, Analyt. Chem., 1975, 47, 171. 155 R. D. Wilson and R. Bau, J. Amer. Chem. SOC.,1974, 96, 7601. 156 G. Huttner and W. Gartzke, Chem. Ber., 1975, 108, 1373. 157
210
Organophosphorus Chemistry
Compound (OC)3Mo(HN =PPh&Mo(C0)3,3C4HsO
Comments Unusual co-ordination by each N to two Mo atoms, i.e.
P&&--NH
i"
P-N
Ref. 157
1.604(40) A
! Mo Ph,P=N
#-$
S
\
N-S
//
P-N 1.645(10) A; LPNS 121.0(6)'
158
Phosphorus is four-co-ordinated, and not five-co-ordinated as previously suggested. P-N 1.562(6) A; LSNP 121.0(5)'
159
Ring has twisted chair conformation; P-N 1.596(8) A; LNPN 114.5(4)*
160
PN ring has slight 'boat' conformation; P-N 1.567(5) 8, PN ring has irregular slight 'chair' conformation; P-N 1.580(15) A PN ring has slight 'sofa' conformation, P-N (endo) 1.568(2) and 1.576(5) 8, One nitrogen atom in each ring weakly bonded to iodine, which causes a slight lengthening of the adjacent P-N bonds (1.64 A). The other P-N bonds have a mean of 1.598 A Crystal data only
161
p-Xylene held within channels in crystal lattice. Mean P-N 1.57 8,
165
t p-xylene (as clathrate)
J. S. Miller, M. 0. Visscher, and K. G. Caulton, Inorg. Chem., 1974, 13, 1632.
lS7 159
161 163
164
1~
E. M. Holt and S. L. Holt, J.C.S. Dalton, 1974, 1990. J. Weiss, I. Ruppert, and R. Appel, 2. anorg. Chem., 1974, 406, 329. P. A. Tucker and J. C. van de Grampel, Acfa Cryst., 1974, B30,2795. P. Clare, T.J. King, and D. B. Sowerby, J.C.S. Dalton, 1974, 2071. F. R. Ahmed and E. J. Gabe, Acta Cryst., 1975, B31, 1028. P. L. Markila and J. Trotter, Canad. J . Chem., 1974, 52, 2197. K. R. Waerstad and G. H. McClellan, J . Appl. Cryst., 1974, 7 , 446. H. R. Allcock, M. T. Stein, and E. C. Bissell, J. Amer. Chem. Soc., 1974, 96, 4795.
161 162 163
164
211
Phosphazenes Compound N4PWNMe2)4 (2-trans-4-cis-6-trans-8:) N4P4C14Ph4 (2,2,6,6:) N4P4C14Ph4 (2-cis-4-trans-6-trans-8:) N4P4Ph8
Comment Ref: 166 PN ring close to ‘saddle’ conformation. Mean P-N (endo) 1.557 8, 167 PN ring has ‘saddle’ conformation; P-N 1.553, 1.591 A 168 PN ring has ‘saddle’ conformation; P-N 1.553, 1.591 A 169 PN ring has S4 symmetry; P-N 1.590 A. Isostructural with N4As4Ph~,also reported in this paper Polymer chain has cis-planar conformation, 170
P-N bond lengths not established
M. J. Begley, D. Millington, T. J. King, and D. B. Sowerby, J.C.S. Dalton, 1974, 1162. G. J. Bullen and P. E. Dann, Acta Cryst., 1974, B30, 2861. A. H. Burr, C. H. Carlisle, and G. J. Bullen, J.C.S. Dalton, 1974, 1659. M. J. Begley, D. B. Sowerby, and R. J. Tillott, J.C.S. Dalton, 1974, 2527. 170 S. M. Bishop and I. H. Hall, Brit. Polymer J., 1974, 6, 193.
168
16’ 168 16@
11
Photoc hem ical , Radical , and Deoxyg enat io n Reactions BY R. S. DAVIDSON
1 Photochemical Reactions The very familiar chemiluminescent reaction of elemental phosphorus with oxygen in the presence of water has been re-examined.l The emission is markedly affected by the use of deuterium oxide instead of water, and this observation was interpreted as supporting the view that the emitting species in the aqueous system are the (PO), excimer and the HPO radical. Further interest has been shown in the photochemistry of ylides.2The ratio of the products formed on irradiation of (1) was found, as in previously examined cases, to be dependent on wavelength. Cleavage to give benzene is favoured by the use of lower wavelengths (< 290 nm) and formation of 2,3-dimethylbut-Zene is favoured by light of long wavelength (> 350 nm). The question as to whether the butene is formed via a carbene was examined by carrying out the reaction in isobutene as solvent. Since formation of a cyclopropane was not observed, it appears that the ylide is not photodecomposed to a carbene, and the results of other experiments support this conclusion. It has therefore been proposed that butene formation occurs via a biradical(2). This result is in stark contrast to the one reported last year, which concerned the ylide (3).3 Ph3P;CMe,
b+
PhH + Me,C=CMe,
+ Me,CHCHMe,+ MeCH-CH,
+
Ph,P
Ph, fi \
Ph,t-kMe,
7
I
2Ph,P
+ Me,C=CMe,
./ C W Ph, P
(2) Ph,P=CHCOPh
(3)
The use of light-sensitive protecting groups has been exploited in nucleotide ~ynthesis.~ o-Nitrobenzyl phosphates are readily cleaved on irradiation, to give o1 2
3 4
R. J. Van Zee and A. U. Khan, J. Amer. Chem. Soc., 1974,96, 6805. H. Durr, D. Barth, and M. Schlosser, Tetrahedron Letters, 1974, 3045. R. R. da Silva, V. G. Toscano, and R. G. Weiss, J.C.S. Chem. Comm., 1973, 567. M. Rubinstein, B. Amit, and A. Patchornik, Tetrahedron Letters, 1975, 1445.
212
21 3
Photochemical, Radical, and Deoxygenation Reactions
nitrobenzaldehyde and the unprotected phosphate. Removal of the aldehyde, which causes complicating side reactions, was accomplished by having an insoluble polymer derivative of semicarbazide present in the reaction mixture. Formation of (4) illustrates the steps in a typical synthesis.
OAc
OAc Ar = o-Nitrobenzyl T = Thymidine
H,03POCH,
T
OHO + Q
Aryl phosphonates are formed in good yield by irradiation of the potassium salts of dialkyl phosphites in liquid ammonia solution containing an aryl iodide.6 The reaction was suggested as being initiated via photoinduced electron transfer from the phosphite anion (5) to the iodide. Since liquid ammonia is particularly good at (RO),PO + ArI kv, (RO),P6 + A r i (5 )
ArI’
Ar*(OR),
I 0-
-
+ ArI
A;
+I-
* ArP(OR),
II 0
+ ArI’
solvating electrons, it is possible that the electron-transfer reaction is a two-step process. The fact that photoinduced electron ejection from monophenyl phosphate anions in aqueous solution has been observed supports this suggestion. The formation of products on photolysis of trimethyl phosphate in degassed aqueous solutions is grossly inefficientwhereas in the presence of oxygen dimethyl phosphate formation occurs, with a quantum yield of 0.11.’ Since phosphate (6) is formed in degassed solutions, it has been suggested that the photo-oxidation reaction 5 6
J. F. Bunnett and X. Creary, J. Org. Chem., 1974,39, 3612. M. Sacher and N. Getoff, Oesterr. Akad. Wiss., Math-Naturwiss. Kh., Sitzungsber., Abt. 2, 1974,184, 175 (Chem. Abs., 1974,82, 49 819f). H.P. Benschop and M. Halmann, J.C.S. Perkin ZZ, 1974, 1175.
8
214
Organophosphorus Chemistry (MeO), POkH,
(MeO), PCH$H, P(OMe),
[ (MeO),PO]*
II
II 0
II 0
0
+ (MeO),PO
__f
(MeO),f-OH
f
(MeO),P&H,
II
0
(MeO),fOH
(MeO),P&I-I,
II 0
-%
4, (MeO),PO + HO;
(MeO),POCH,Od
(MeO),POC&O,H
ll 0
II 0
(MeO),POC&O,H
II 0
(MeO),Pd
II 0
+
(MeO),PkIE,
ll
0
+ (MeO),PO' + CH,O +
II
0
.:
(MeO),POH + (MeO),P&H,
ll
0
II
0
involves (7). Presumably this radical is formed via the excited phosphate group, which abstracts hydrogen from a methyl group. In the absence of oxygen the back hydrogen-transfer reaction may be very efficientwhereas, in its presence, the radicals can be trapped to give radicals which can undergo hydrogen-abstraction reactions. Photodecomposition of 00-dimethyl O-3-methyl-4-nitrophenyl phosphorothioate in aerated aqueous solutions involves solvolysis to give the phenol and photooxidation of the benzylic methyl to a carboxy-group.s The latter reaction probably results from intramolecular attack by the excited nitro-group upon the methyl group. The synthesis of 2-phosphanaphthalene has been r e p ~ r t e d As . ~ might be anticipated, its electronic absorption spectrum is similar to that of naphthalene. Similarities are also observed in the fluorescence and phosphorescence spectra of the two compounds. A further study has been made of the quenching of the fluorescence of anthracenes by triphenylphosphine. Rate constants for quenching were determined for a number of substituted anthracenes and attempts made to correlate these values with the o-values for the substituents.1° A linear relationship for all substituents was not observed, and this may be due to the fact that, for the very fast processes, corrections were not made for transient diffusional effects.ll The authors suggested that nonlinearity was due to steric effects. Irradiation of the l-azidophosphetan oxide (8) leads to products by a ring expansion and a ring-opening reaction.12The latter is most readily rationalized as occurring via a nitrene intermediate, A metaphosphonimidate (9) appears to be the most H. Ohkawa and N. Mikami, Agric. and Biol. Chem. (Japan), 1974,38,2247 (Chern. Abs., 1974, 82, 97 374d). H. G. de Graaf and F. Bickelhaupt, Tetrahedron, 1975, 31, 1097. lo M. E. R. Marcondes, V. G . Toscano, and R. G. Weiss, Tetrahedron Letters, 1974, 4053. l1 R. M. Noyes, Progr. Reaction Kinetics, 1961, 1, 129. l 2 M. J. P. Harger, J.C.S. Perkin I, 1974, 2604. 8
215
Photochemical, Radical, and Deoxygenation Reactions
likely candidate for an intermediate in the ring-expansion reaction. This could be formed either via the nitrene or by migration of carbon from the phosphorus to the nitrogen atom as nitrogen is being expelled from the excited azide group. Further evidence for the phosphonimidate intermediate comes from the observation that irradiation of either the cis- or trans-isomer of (10) gives exactly the same mixture of cis- and trans-isomers of (lla) and (llb).13 Me
Me
Me
Direct irradiation of the phosphonates (12) and (14) leads to the formation of (13) and (15), respectively, i.e. collapse of the intermediate 1,3-biradical to a cyclopropane successfully competes with bond r0tati0n.l~On triplet sensitization, (12) and (14) give mixtures of (13) and (15). The ratio of the yields of (13) and (15) is dependent upon the size of the R group. Thus when R = Me, (13) gives a 90% yield of (12), whereas when R = Ph it gives a 50% yield of (12). These results have been discussed in terms of steric interactions between the R group and the bridgehead C-H bonds.
Q (1 2 ) 1s 14
J. Wiseman and F. H. Westheimer, J. Amer. Chem. SOC.,1974, 96, 4262. C. Benezra and N. D. Tho, Tetrahedron Letters, 1974, 4437.
216
0rganophosphorus Chemistry
The chemistry of phosphonylcarbenes has been reviewed.15 This species can be generated by photochemical or thermal decomposition of the appropriate diazocompound. Photolysis of (16) generates a carbene which rearranges to (17).l6 This
1
Ph
/OH PhP l'OMt3 0
+
MeOH
(19)
R4
R3
c=c,
\
R4
can be trapped by q9-unsaturated carbonyl compounds. The adducts (1 8) undergo photolysis to give dienes and (19). If the reaction is conducted in methanol, (19) reacts to give (20). Thermal reaction of (21) with (22) leads to both (2 2) and (2 + 4) cycloaddition products.
+
Ph
I
l5 16
M. Regitz, Angew. Chem. Internat. Edn., 1975, 14, 222. H. Eckes and M. Regitz, Tetrahedron Letters, 1975, 447.
Photochemical, Radical, and Deoxygenation Reactions
217
On triplet sensitization, the phosphine oxide (23) undergoes an intramolecular cycloaddition reaction to give the cage-compound (24).l In contrast, direct irradiation leads to fragmentation. If methanol is used as solvent, (25) is produced, and Ph I
hv
PhCO*
O tH ‘ TPh =
O
this suggests that phenylphosphinidene oxide is an intermediate. It is interesting to note that the fragmentation reaction successfully competes with photoreduction of the double bonds.18 2 Phosphinidenes and Related Species Products from the dechlorination of phenylphosphonothioicdichloride by magnesium in the presence of 1,3-dienes have been investigated.lBTheir formation can be rationalized as occurring via phenylphosphinidene sulphide. The reaction of this species with cyclohexa-1,3-diene in THF solution not only gives the expected 1,4addition product but also (26), which is formed by the reaction of the phosphinidene with the solvent. Dechlorination of phenylphosphonic dichloride in the presence of 2,3-diphenylbuta-l,3-dienegives (28) and (29), and the zwitterionic compound (27) was suggested as being an intermediate. The reaction of phenylphosphinidene oxide with methanol has already been alluded t0.l’
17 18 19
H. Tomioka, Y . Hirano, and Y . Izawa, Tetrahedron Letters, 1974, 4477. H. Tomioka and Y . Izawa, Tetrahedron Letters, 1973, 5059. S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, Bull. Chem. SOC.Japan, 1975, 48, 546.
Organophosphorus Chemistry
218
3 The Reaction of Reactive Intermediates with Phosphorus-containing Compounds Benzyne reacts with 2-phenyl-1-phosphanaphthaleneto give dibenzophosphabarrelene.20The trapping of keto-carbenes by phospholes has been the subject of an extensive investigation.21Thermal decomposition of the diazo-compound (30) in the
Ph
OP h No /
Ph t
+
/
t
/
presence of 1,3,5-triphenylphospholeyielded the ylide (31). This decomposed on heating to give (32). Attempts were also made to trap the keto-carbene, derived by dehydrobromination of 2-hydroxybromobenzene, with 1,3,5-triphenylphosphole. Formation of 1,4-diphenylnaphthalene(33) in a 34 % yield was observed. However, treatment of the oxide (34) with hydrogen bromide also yielded (33) but in a lower yield. It thus appears that at least some (33) is derived from the keto-carbene. Use of a suitably labelled bromophenol would remove the ambiguity. Ketophosphonates, e.g. (35) and (36), have been shown to trap the 1,3-dipoles derived from 2H-a~irines.~~ 20
21 22
G. Mark1 and K. H. Heier, TetrahedronLetters, 1974, 4369. J. I. G. Cadogan, R. J. Scott, and N. H. Wilson, J.C.S. Chem. Comm., 1974, 902. N. Gakis, H. Heimgartner, and H. Schmid, Helv. Chim. Acta, 1975, 58, 748.
219
Photochemical, Radical, and Deoxygenation Reactions
+a /
PhP=O
/
t
t
Ph
(33)
2
P h oP P h
/ No
Ph
A0
Ph
(34)
4 Radical Reactions
A wide variety of phosphino radicals have been prepared in rigid matrices and their structures investigated by e.s.r. s p e ~ t r o s c o p y . ~The ~ - ~similarity ~ in 31Pcoupling constants for all the radicals demonstrates that there is little tendency for the electron .~~ have been made on the molecular to be delocalized into the l i g a n d ~Calculations geometries of phosphino radicals using INDO approximations.2s 23 24
25
26
B. W. Fullam, S. P. Mishra, and M. C. R. Symons, J.C.S. Dalton, 1974, 2145. M. Geoffroy, E. A. C. Lucken, and C. Mayeline, Mol. Phys., 1974, 28, 839. T. W. Cook,J. S. Vincent, I. Bernal, and F. Ramirez, J. Chem. Pliys., 1974, 61, 3479. A. Hudson and J. T. Wiffen, Chem. Phys. Letters, 1974, 29, 1 13.
Organophosphorus Chemistry
220
The photoaddition of tetrafluorobiphosphine to a variety of olefins has been The ionization potential of the biphosphine has been determined as 57 k 10 kcal mo1-1.28 Dimethylphosphine reacts, on irradiation, with hexafluoroFrom a propene, to give cis- and trans-dimethylpentafluoropropenylphosphine~.~~ consideration of the experimental conditions it was proposed that reaction occurred via the zwitterionic intermediate (37). Tetramethylbiphosphinealso appears to add
4 (37) CF3CF=CFPMe,
cis and trans
to the olefin by an ionic mechanism. Addition of less nucleophilicphosphino radicals, e.g. hexafluorophosphino radicals, to electron-deficient olefins occurs via a radical process. Further studies have been made on phosphoranyl radicals of the type ( 3 Q 3 0 The extent to which the spin density is localized in the biphenyleneportion of the molecule is determined by the electron affinities of R1 and R2.In a similar study on phosphoranyl radicals of the type (39),31the electronegativity of each of the ligands R1,
R2,and R3was shown to control the amount of spin density in the phenyl ring, and hence the geometry of the radical. That spin density does reside on the phenyl ring when R1 = But0 and R2 and R3 = OEt was shown by the fact that, when a pentadeuteriophenyl group was employed, hyperfine coupling to deuterium was observed. Of the many radicals examined, the only one in which spin density on the phenyl was not observed was the one in which R1 = ButO and R2and R3 = C1. It was suggested that, the greater the ability of the ligands R1,R2,and R3to stabilize a positive charge on phosphorus, the greater the likelihood that the electron density resides on the phenyl ring. An extremely detailed study has been made of the radical anion of phosphorus oxy~hloride.~~ By utilizing a single crystal of the oxychloride it 27 28
29
30 31 32
J. G. Morse and K. W. Morse, Inorg. Chem., 1975, 14, 565. C. R. S. Dean, A. Finch, P. J. Gardner, and D. W. Payling, J.C.S. Faraduy 1, 1974, 1921. I?. Cooper, R. Fields, and R. N. Haszeldine, J.C.S. Perkin I, 1975, 702. R. Rothuis, J. J. H. M. Font Freide, J. M. F. van Dijk, and H. M. Buck, Rec. Truu. chim., 1974, 93, 128. A. G . Davies, M. J. Parrott, and B. P. Roberts, J.C.S. Chem. Comm., 1974, 973. T. Gillbro and F. Williams, J. Amer. Chem. SOC.,1974, 96, 5032.
Photochemical, Radical, and Deoxygenation Reactions
22 1
proved possible to do a complete analysis of the e.s.r. spectrum of the radical anion. It was found that the unpaired electron is largely distributed over the apical corbitals. The radical can be represented by structure (40), which emphasizes the extent to which the unpaired electron is delocalized into the apical bonds. Structure (41) illustrates the distribution of spin density. By the use of deuteriated t-butoxyl
0
0.29 Cl C1%*
I*,C' D P
po-
x?'
c1
0.29 C1
0
radicals it has been shown that the p-scission reaction of the tetra-t-butoxyphosphoraryl radical occurs randomly, i.e. there is no preference for the attacking radical to be the source of the t-butyl radicals produced in the ,%scission Thus pseudorotation of the phosphoranyl radical competes effectively with the &scission reaction. In contrast, attack of t-butoxyl radicals upon phosphite (42) gives a phosphoranyl radical which eliminates a t-butyl radical before pseudorotation occurs.34This is a further illustration of the profound effects that incorporation of ring systems into phosphoranyl radicals can have upon the process of pseudorotation. Phosphoranyl and dialkoxyphosphoryl radicals have been shown to add to 1,l-dit-butylethylene to give very stable radicals of the type (43).35Dialkoxylphosphoryl radicals also add to imines, e.g. (M),and to nitrites (45) to give stable radical^.^^ It is
R
33 34
35
36
D. Griller and K. U. Ingold, J. Amer. Chem. SOC.,1975, 97, 1813. H. W. Tan and W. G . Bentrude, J. Amer. Chem. SOC.,1974,96, 5950. D. Griller and K. U. Ingold, J. Amer. Chem. SOC.,1974, 96, 6715. R. A. Kaba, D. Griller, and K. U. Ingold, J. Amer. Chem. SOC.,1974, 96, 6202.
222
Organophosphorus Chemistry
found that in the preferred conformation of the radicals there is eclipsing of the orbital containing the odd electron and the P-N a-orbital and the P-C o-orbital in (43). The that this eclipsing does not lead to a hyperconjugative interaction in these and closely related radicals has been refuted3' and the arguments have been countered. There have been several synthetic applications of the addition of dialkylphosphinyl radicals to 0lefins.~~9 39 The reaction of dialkoxyphosphoryl radicals with fluoro-substituted alkyl bromides has been used to prepare fluoroalkyl radicals.40The radical anion of the dianion of PP'-diphenyl ethylenebiphosphine has been prepared and its e.s.r. spectrum a n a l y ~ e d . ~ ~ Phosphorus trichloride and pentachloride have been shown to act as effective catalysts for the radical chlorination of alkanes, cycloalkanes, and a r a l k a n e ~A .~~ detailed product analysis has been made of the reactions of a variety of ole fin^^^ and fluoro-olefins44 with phosphorus trichloride in the presence of oxygen. Alkyl and ally1 halides also react with phosphorus trichloride in the presence of oxygen to give phosphonyl and phosphoryl dichloride~.~~ The reaction of n-propyl chloride gave a mixture of products which on treatment with ethanol yielded (46)-(49). The kinetics MeCHCH.$l
I
MeC&CH-P(OEt),
I
a (46 1
II
0
MeCHC&Q
I
O=P(OE t)2 (47)
C&CK?C4~
I
O=P(OE tI2 (48)
b-P(OEt),
I1
0 (49)
of hydrogen abstraction by phenyl radicals from a variety of compounds containing P=O bonds have been examined.46In general, the compounds are relatively unreactive, and the radicals produced tend to disproportionate. Solvated electrons have been shown to react with nucleotide (50), and the phos-
37
38 39 4O
41 42
43
44 45 48
M. C. R. Symons, Tetrahedron Letters, 1975, 793. M. Finke and H.-J. Kleiner, Annalen, 1974, 741. H.-J. Kleiner, Annalen, 1974, 751. K. S. Chen, P. J. Krusic, P. Meakin, and J. K. Kochi, J. Phys. Chem., 1974, 78, 2014. A. G. Evans, J. C. Evans, and D. Sheppard, J.C.S. Perkin ZZ, 1975, 643. G. Olah, P. Schilling, R. Renner, and I. Kerekes, J . Org. Chem., 1974, 39, 3472. C. B. C. Boyce, S. B. Webb, and L. Phillips, J.C.S. Perkin I , 1974, 1650. C. B. C. Boyce, S. B. Webb, L. Phillips, and I. R. Ager, J.C.S. Perkin I , 1974, 1644. Y. Okamoto, T. Okada, and H. Sakurai, BiilI. Chem. SOC.Japan, 1975,48, 484. A. Ya. Levin, E. K. Trutneva, and B. E. Ivanov, Zhur. obshchei Khim., 1974,44, 1443 (Chem. Abs., 1974, 81, 168 868h).
223
Photochemical, Radical, and Deoxygenation Reactions
phate residue is released.47The electrons are thought to attack the purine group initially. Thermal decomposition of 1,3-diphenyItriazene in perchloric acid containing triphenylphosphine and a monosubstituted benzene gives biaryls and (52).48 The azo-compound (51) has been proposed as being the precursor of (52) and the aryl Ph'
PhN=NNHPh
Ph,P HC,O,+
+ P h ? + N,
PhN=N--hPh, (51)
c10;
PhNHNH;Ph,
ClOi
(52)
radicals. Optically active tetra-arylphosphonium salts have been prepared by the reaction of an optically active triarylphosphine with an aryl iodide in the presence of a cobalt 5 Deoxygenation Reactions The use of deoxygenation reactions in olefin synthesis, and the deoxygenation of epoxides, ozone, and nitro-compounds, have been the subjects of a comprehensive review.6o The deoxygenation of epoxides by tributylphosphine selenide has been shown to involve an episelenide.61By the use of mild reaction conditions it proved possible to isolate compounds such as (53). Photo-oxygenation of (54) gives the peroxide (55) in high yield.s2This, on reaction with triphenylphosphine, yields (56) and (57). A wide variety of 1,Z-dioxetans have been prepared and their reactions with triphenylphosphine studied.s3 Dioxetans derived from alkenes yield epoxides and allylic alcohols whereas those derived from cycloalkenes give diketones (formed by ring opening) and allylic alcohols. Recently, 1,2-dioxetanshave been isolated from photooxygenation reactions of e n a r n i n e ~These . ~ ~ react with triphenylphosphine to give a-diketones.
47 48 49
50
5l 52
53
J. A. Raleigh and R. Whitehouse, J.C.S. Chem. Comm., 1975, 305. G. De Luca, C. Panattoni, G. Renzi, and L. Toriolo, Tetrahedron Letters, 1974, 2463. R. Luckenbach, Tetrahedron Letters, 1975, 1673. J. I. G. Cadogan and R. K. Mackie, Chem. SOC.Rev., 1974,3, 87. T. H. Chan and J. R. Finkenbine, Tetrahedron Letters, 1974, 2091. Y . Ito, M. Oda, and Y. Kitahara, Tetrahedron Letters, 1975, 239. K. R. Kopecky, J. E. Filby, C. Mumford, R. A. Lockwood, and J. Ding, Canad.J. Chem., 1975, 53, 1103.
54
H. H. Wasserman and J. Terao, Tetrahedron Letters, 1975, 1735.
224
Organophosphorus Chemistry
0
Ph,P
(56)
Thermal decomposition of phosphite-ozonides has been used as a method of generating singlet oxygen. However, the reaction can be complicated by the formation of zwitterionic intermediate^.^^ This problem has been overcome by the use of phosphite (58).56The ring system prevents the pseudorotation processes that can lead
(58)
to the ozonide decomposing by an ionic pathway. Several olefins have successfully been oxygenated by means of the ozonide. Several phosphites have been shown to be oxidized to phosphates by singlet oxygen,57and some relative reactivities have been determined. The synthesis of tetrathiofulvalenesis a subject which has attracted a considerable amount of attention since the discovery that the charge-transfer complexes formed between these compounds and 7,7,8,8-tetracyanoquinodimethane exhibit high electrical conductivity.68The usual pattern of the synthesis involves formation of a species such as (59), which is then either deoxygenated, desulphurized, or deselenated to give the required ~ o i n p o u n dThe . ~ ~reaction of (60) is an example, and others will be found later in the chapter.
(59) 55 56 57 58
69
x
= 001
s
(60)
L. M. Stephenson and D. E. McClure, J. Amer. Chem. SOC.,1973, 95, 3074. A. P. Schaap, K. Kees, and A. L. Thayer, J. Org. Cliem., 1975,40, 1185. P. R. Bolduc and G. L. Goe, J . Org. Chem., 1974,39, 3178. J. P. Ferraris, D. 0. Cowan, V. Walatka, and J. H. Perlstein, J . Amer. Chem. Soc., 1973,95,948. M. G. Miles, J. D. Wilson, D. J. Dahm, and J. 13. Wagenknecht, J.C.S. Chem. Comm., 1974, 751.
Photochemical, Radical, and Deoxygenation Reactions Ph
225
Ph
(62)
(61)
The deoxygenations of 1,2-diphenyImaleic anhydride to give (61),60 and of sulphoxides by (62),61have been reported. The latter reaction is proposed as occurring via nucleophilic attack of (62) upon the sulphoxide, even though carbon tetrachloride is used as the solvent. Once again there have been a number of synthetic applications of the deoxygenation of nitro-compounds.62The question as to whether free nitrene intermediates are involved has again been looked at, and no firm conclusion reached.63Deoxygenation of a variety of rneta-substituted nitrobenzenes in the presence of diethylamine has been shown to give a mixture of two azepines. Exactly the same mixture is obtained if the appropriately substituted azides are photolysed. Intramolecular deoxygenation of (63) leads to benzofurazan formation.64
A 150°C)
Ph[TPh Ph’
PhCONHOhh, X (64)
-
+
0 ‘
PhCON: + Ph,PO + HX
Decomposition of salts of the type (64) has been proposed as being a source of aryl-nitrene~.~~ Deoxygenation of acyl nitrites with triphenyl phosphite leads to anhydride and isocyanate formation.6 6 6 Desulphurization Reactions There have been further elegant applications of the desulphurization of sulphides to the synthesis of cy~lophanes,~~ and of the desulphurization of sulphenic estersYss 60
C. W. Bird and D. Y . Wong, Tetrahedron, 1975, 31, 31.
M. Drew, Y. Leroux, and P. Savignac, Synthesis, 1974, 7 , 506. T. Kametani, F. F. Ebetino, and K. Fukumoto, Tetrahedron, 1974, 30, 2713; T. Kametani, F. F. Ebetino, and K. Fukumoto, ibid., 1975, 31, 1241; A. J. Nunn and F. J. Rowell, J.C.S. Perkin I , 1975, 629. e3 T. de h e r , J. I. C . Cadogan, H. M. McWilliam, and A. Rowley, J.C.S. Perkin II, 1975, 554. G4 J. I. G . Cadogan, R. J. Scott, R. D. Gee, and I. Gosney, J.C.S. Perkin I , 1974, 1694. 65 S. Bittner, S. Grinberg, and I. Kartoon, Tetrahedron Letters, 1974, 1965. V. L. Isaev, L. Yu Mal’kevich, V. G. Platonov, R. N. Sterlin, and I. L. Kninyants, Zhur. Vses. Khim. 0 - c a , 1974, 19, 477 (Chem. A h . , 1974, 81, 135 6OOp). 67 M. W. Haenel, Tetrahedron Letters, 1974, 3053. 68 J. G. Miller, W. Kurz, K. G. Untch, and G. Stork, J . Amer. Chem. SOC., 1974, 96, 6774. 61
62
226
0rganophosphorus Chemistry
derived from allylic sulphoxides by a 2,3-sigmatropicshift, to the synthesis of prostaglandin derivatives. Desulphurization of (65),ss (66),'O and (67) 71 to give the corresponding tetrathiafulvalenes and tetraselenafulvalenes has been accomplished by
heating the compounds in the presence of phosphites. Conflicting mechanisms have been put f o r ~ a r d Good . ~ ~ evidence ~ ~ ~ exists to support the conclusion that a zwitterionic intermediate such as (68) is involved,sgand the question is whether this gives the olefin via an ionic process or a carbene intermediate. Triphenyl phosphite has been used to advantage since it precludes rearrangements such as that of (69) to (70).70 Other desulphurization reactions studied 72-74 include those of thioketals 73 and diary1 disulphides.74 The latter involved a stopped-flow kinetic study. At both high and low pH, reaction (1) is the rate-determining step. At intermediate pH values the reverse of reaction (1) (k-& becomes important and complicates the kinetics. Ph3P
+
ki
ArSSAr+Ph3$SAr
+
SAr
(1)
k-i
Ph$SAr 69
io 72 73 i4
+
k2
HzO+Ph3PO
+
ArS-
+
2H+
(2)
G . Scherowsky and J. Weiland, Chem. Ber., 1974, 107, 3155. Z . Yoshida, T. Kawase, and S . Yoneda, Tetrahedron Letters, 1975, 331. K. Bechgaard, D. 0. Cowan, and A. N. Bloch, J.C.S. Chem. Comm., 1974, 937. M. N. Campbell and G. Johnson, J.C.S. Chem. Comm., 1974, 974. Z. Yoshida, T. Kawase, and S . Yoneda, Tetrahedron Letters, 1975, 235. L. E. Overman, D. Matzinger, E. M. O'Connor, and J. D. Overman, J. Amer. Chem. SOC.,1974, 96, 6081.
221
Photochemical, Radical, and Deoxygenation Reactions
7 Deselenation Reactions Deselenation reactions have also been used in the synthesis of tetraselenafulvalenes, e.g. the reaction of (71) with phosphites and phosphines gives (72).75Other deselenation reactions include those of (73) 7 6 and of diselenides (74).77v7 8 The latter reaction appears to go via a free-radical mechanism. Diethyl ditelluride does not appear to react with methyldiphenylphosphine.7 7
Ph,POMe
*
I1
P$POMe
+
[
-+
K]--NC]
K F C N
Se
Et,Se,
(74)
hu, EtSe'
Ph,PMe
Ph&eEt
I Me
-+ PbP=Se
I Me
+ Et'
El + EGSe, -+ Et,Se + EtSe'
75 76
77 78
E. M. Engler and V. V. Patel, J . Amer. Chem. SOC.,1974, 96, 7376. W. J. Stec, T. Sudol, and B. Uznanski, J.C.S. Chem. Comm., 1975, 467. R. J. Cross and D. Millington, J.C.S. Chem. Comm., 1975, 455. I. A. Nuretchnov, E. V. Bayandina, and G. M. Vinokurova, Zhur. obshchei Khim., 1974, 44, 2588 (Chem. A h . , 1975,82, 9 7 621g).
I2 Physical Methods BY J.
C. TEBBY
The abbreviations PIII, P I V , and P V refer to the co-ordination number of phosphorus, and the compounds in each subsection are usually dealt with in this order. A number of relevant theoretical and inorganic studies are included in this chapter. In the formulae the letter R represents hydrogen, alkyl, or aryl, X represents electronegative substituents, Ch represents the chalcogenides (usually oxygen and sulphur), and Y and Z are used to indicate a wide variety of substituents. The use of computers to aid the interpretation of the spectra of organic compounds has been reviewed.l The limitations of the algorithmic methods mean that at present library search methods which require computer-readable data files are likely to be more useful. 1 Nuclear Magnetic Resonance Spectroscopy The number of studies of biologically important phosphorus compounds by n.m.r. spectroscopy continues to grow. Reports have appeared on the conformations and equilibria of nucleotides,2 RNA,3 phospholipid^,^ lipoprotein^,^ and many other naturally occurring compounds containing phosphorus.6 Metabolic reactions within intact bio!ogical tissue have been followed by 31P n.m.r. spectroscopy.' Levels of T. Clerc and F. Erni, Fortschr. Chem. Forsch., 1973, 39, 91. D. J. Wood, F. E. Hruska, and K. K. Ogilvie, Canad. J. Chem., 1974, 52, 3353; R. H. Sarma, C . H. Lee, F. E. Evans, N. Yathindra, and M. Sundaralingam, J. Amer. Chem. SOC.,1974,96, 7337; F. E. Evans and R. H. Sarma, Biopolymers, 1974,13,2117; T. Glonek, R. A. Kleps, and T. C. Myers, Science, 1974, 185, 352; S. V. Zenin, Doklady Akad. Nauk S.S.S.R., 1974, 217, 615; I. Feldman and V. Wee, Biochemistry, 1974,13, 1836; S . V. Zenin, V. A. Polyakov, A. F. Rusak, and G. B. Sergeev, Zhur. fiz. Khim., 1974, 48, 834; D. Perahia, B. Pullman, and A. Saran, Biochim. Biophys. Acta, 1974, 340, 299; 1974, 353, 16. 3 L. M. Weiner, J. M. Backer, and A. L. Rezvukhin, F.E.B.S. Letters, 1974, 41, 40. 4 M. P. N. Gent and J. H. Prestegard, Biochemistry, 1974, 13, 4027; H. Richard and B. Clin, Compt. rend., 1974,278, C, 1275; L. I. Barsukov, Yu. E. Shapiro, A. V. Viktorov, V. I. Volkova, V. F. Bystrov, and L. D. Bergelson, Biochem. Biophys. Res. Comm., 1974,60,196; D. Abernethy, T. J. Fitzgerald, and E. J. Walaszek, ibid., 59, 535; E. G. Finev, J. Magn. Resonance, 1974, 13, 76; J. A. Berden, P. R. Cullis, D. I. Hoult, A. C . McLaughlin, G. D. Radda, and R. E. Richards, F.E.B.S. Letters, 1974, 46, 5 5 ; R. J. M. Smith and C. Green, Biochem. SOC.Trans., 1974, 2, 962. 5 G. Assmann, E. A. Sokoloski, and H. B. Brewer, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 549; T. Glonek, T. 0. Henderson, A. W. Kruski, and A. M. Scanu, Biochim. Biophys. Acta, 1974, 348, 155. 6 H. Richard, J. Dufourcq, and C. Lussan, F.E.B.S. Letters, 1974, 45, 136; C. H. Lee and R. H. Sarma, J. Amer. Chem. SOC.,1975,97,1225; R. Katz, J. C . Herman, and D. F. Johnson, Biochem. Biophys. Res. Comm., 1974, 58, 316; J. Wiechelman, S. Charache, and C. Ho, Biochemistry, 1974, 13,4772; Y. Kyogoku, Chem. Abs., 1974, 81, 146 954. 7 D. I. Hoult, S. J. W. Busby, D. G. Gadian, G. K. Radda, R. E. Richards, and P. J. Seeley, Nature, 1974, 252, 2 8 5 ; T. 0. Henderson and A. J. R. Costello, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 2487.
2
228
Physical Methods
229
creatine phosphate, sugar phosphate, phospholipids, ATP, and inorganic phosphate were monitored in the leg muscle of a rat. The 31Psignal of phosphates has also been used to determine the intercellular P H . ~A review of n.m.r. studies of phosphorus compounds has been p~blished.~ Chemical Shifts and Shielding Effects.-Phosphorus-31. Positive 31P chemical shifts ( 8 ~ reported ) in this chapter are upfield from 85 % phosphoric acid. Tetrahydroxyphosphonium perchlorate, formed from a 0.2 mol 1-1 solution of crystalline phosphoric acid in aqueous 14 % perchloric acid, gives a very narrow (<0.11 Hz) signal only 2.7 Hz upfield of 85 % phosphoric acid.1° It is recommended as a good locking substance. 8p of PI and PI1 compounds. The chemical shifts of aminocarbophosphyl derivatives (1 ; Y = H, Ph, Bu, or COCH,Cl) are in the range -4.66 to -0.53 p.p.m.ll and those of lithium diorganylphosphides (2; R = alkyl or aryl) are in the range 17.8141 p.p.m.12 The Fourier-transformed spectrum of solid P,S3 corresponds to an ABQ spectrum, showing that spectral narrowing by nuclear motion can be sufficiently large to give spectra exhibiting spin multiplets as well as chemical shifts.13
8~ ofPII1 compounds. The HPH bond angles of phosphine have been calculated to be 94.3" from the n.m.r. parameters measured in liquid-crystal A study of primary phenylphosphines (3) showed that both electron-donor and electronwithdrawing substituents caused upfield shifts. Therefore non-polar contributions
appear to be much more important than any polar contribution.ls The chemical shifts were very sensitive to the presence of ortho-substituents, the upfield shifts being about twice those of the correspondingpara-substituents. Empirical equations relating 8~ and substituent effects of methylphosphines and silylphosphines (4) have been published.le Four- and five-membered cyclopolyphosphines (5; n = 4) and (5; n = 5) may be distinguished by their chemical shifts (+ 60 L- 10 and - 5 k 15 p.p.m., respectively) and by the coupling patterns of their lH-decoupled spectra." R. B. Moon and J. H. Richards, J . Biol. Chem., 1973, 248, 7276. G . Mavel, 'Annual Reports on N.M.R. Spectroscopy', Academic Press, New York, 1973, Vol. 5B. 10 T. Glonek and J. R. Van Wazer, J. Magn. Resonance, 1974,13, 390. 11 I. S. Matveev, Zhur. strukt. Khim., 1974, 15, 145. 12 S. 0. Grim and R. P. Molenda, Phosphorus, 1974, 4, 189. l3 E. R. Andrew, W. S. Hinshaw, and A. Jasinski, Chem. Phys. Letters, 1974, 24, 399. l4 N. Zumbulyadis and B. P. Dailey, J. Chem. Phys., 1974, 60, 4223; Mol. Phys., 1974, 27, 633. l5 L. Maier, Phosphorus, 1974, 4, 41. l6 G. Fritz and H. Schaefer, 2. anorg. Chem., 1974,409, 137. L. R. Smith and J. L. Mills, J.C.S. Chem. Comm., 1974, 808. 8
9
230
Organophosphorus Chemistry
The chemical shifts of the dioxaphosphorinans (6) are dependent on their stereochemistry.l* An axial methoxy-group causes a 3-4 p.p.m. upfield shift, which is probably associated with a 1,3 syn-diaxial interaction. 8~ of PIv compounds. The most positive value of B p for a phosphonium salt (+ 21 p.p.m.) has been recorded for the spirophosphonium salt (7).19 Electron-releasing groups generally shield phosphorus, and a delocalized ground state is believed to
have the same effect2o on PIv compounds. Thus the high-field chemical shift for the salt (7) is evidence for aromatic character and adds weight to the experimental evidence that d,, bonding to phosphorus causes shieldingof the phosphorus atom. The detection of a doublet and asinglet in the31Pn.m.r.spectrumof the salt (8; X = Ph4B-) has been used as evidence for the presence of the two tautomers (8a) and (8b) in DMSO solution, the former predominating.21 A theoretical interpretation of BP of methyl, methoxy, and dimethylamino salts (9) and (10) has been based on polarity parameters,22and the difference of 8~ between equally substituted phosphonium salts and phosphoryl compounds (10) and (11) was found to be a linear function of
aZ3 Replacing R by N, groups in the salts (12; R = Me and Ph) moves 8p upfield in the methyl and phenyl series.24The n.m.r. parameters of some protonated phosphites (13) have been measured. The SP values (- 21 to - 15 p.p.m.) move upfield as neopentoxy-groups are replaced by hydroxy-gro~ps.~~ The chemical shifts of phosphoryl compounds correlate with the sum of the P-substituent inductive constants (.*) if corrections are made for the number of a-hydrogen atoms.26The chemical shifts of M. Haemers, R. Ottinger, D. Zimmermann, and J. Reisse, Tetrahedron, 1973, 29, 3539. R. N. Jenkins, L. D. Freedman, and J. Bordner, J . Cryst. Mol. Structure, 1973, 3, 103. 20 J. C. Williams, J. A. Kuczkowski, N. A. Portnoy, K. S. Yong, J. D. Wander, and A. M. Aguiar, Tetrahedron Letters, 1971, 4749. 2 1 T. A. Mastryukova, Kh. A. Suerbaev, E. I. Matrosov, P. V. Petrovskii, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2593. 2 2 R. Radeglia and H. Teichmann, Z . Chem., 1974,14, 249. 23 R. Radeglia and H. Teichmann, Z . Chem., 1974, 14, 282. 24 W. Buder and A. Schmidt, Chem. Ber., 1973, 106, 3812. 25 H. R. Hudson and J. C. Roberts, J.C.S. Perkin 11,1974, 1575. 2 6 V. E. Bel'skii, L. A. Kudryavtseva, E. I. Gol'dfarb, and B. E. Ivanov, J. Gen. Chem. (U.S.S.R.), 1974,44,2612.
18 19
Physical Methods
23 1
the phosphinimines (14) have been related to substituent The influence of alkyl substituents was attributed to intramolecular co-ordination of /?-methylgroups to the d-orbitals of phosphorus. The change in 8p upon protonation of phosphonyl compounds decreases with the number of oxygen ligands and was found to be zero for trialkyl phosphates.28The decrease was rationalized as being due to increased dn-pn bonding, leading to shielding of the phosphorus nucleus. No such compensating effect occurred for sulphur ligands. Comparisons of SP of phosphonic anhydrides and their sulphur analogues (15) showed that a phosphorus atom bearing
Ch
Ch
II It Me,P - Ch - PMe,
Y
mixed chalcogenidesis more highly shielded than the average of the chemical shifts of the phosphorus groups bearing two oxygen and two sulphur atoms.29This is unusual for two ligands with different electronic properties. The effect of conjugative paraoriented substituents on the chemical shifts of arylphosphonyl chlorides and esters (16; X = Cl or OR) is to shield the phosphorus atom.30Increasing the bulk of the alkoxy-groups in the esters has the same effect. Cyano-groups have been noted for their shielding effe~t,~ld and the 8p of + 28.5 for (17; Y = CN) is in accordance with this effect.32The isocyanide group in (17; Y = NC) has an even greater shielding ~ f34.5 p.p.m.). The increase in shielding upon changing the halogen effect ( 8 of atom through the series F, C1, Br is much greater for the di(pentailuoropheny1) compounds (18; Hal = F, Cl, or Br) than in the t-butyl(pentafluoropheny1) series (19; Hal = F, Cl, or Br).33The six-membered thionophosphites which contain the cyclic ring (20; Y = 0)have Sp values near - 68 p.p.m., compared to 8~ of - 80 to
27 28 29
30 31
32
s3
W. Buchner and W. Wolfsberger, 2. Naturforsch., 1974, 29b, 328. N. K. Skvortzov, B. I. Ionin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1974,44, 209. G. Haegele, W. Kuchen, and H. Steinberger, Z.Naturforsch., 1974, 29, 349. F. M. Kharrazova, T. V. Zykova, R. A. Salakhutdinov, and G. I. Rakhimova, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2621. ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports) The Chemical Society, London, (a) 1970, Vol. 1, Ch. 11; (b) 1971, Vol. 2, Ch. 11; (c) 1972, Vol. 3, Ch. 11; ( d ) 1973, Vol. 4, Ch. 11; (e) 1974, Vol. 5, Ch. 11; (f)1975, Vol. 6, Ch. 11. W. J. Stec, A. Konopka, and B. Uznaliski, J.C.S. Chem. Comm., 1974, 923. M. Fild and T.Stankiewicz, 2. Naturforsch., 1974, 29b,206.
232
Organophosphorus Chemistry
- 85 for the five-membered heterocycles and 8~ of - 59 p.p.m. for the acyclic com. ~ ~chemical p o u n d ~The . ~ ~amide (20; Y = NH) has a 8~ value of - 70 p . ~ . m The shifts of cyclic and acyclic phosphates have been correlated with OPO bond angles. The signals of five-membered cyclic phosphates which have OPO bond angles < 100"appear at 8~values of - 11 to - 22 p.p.m., whereas the signals of phosphates with OPO bond angles > 107" appear at 8~ values of + 2 to 14 ~ . p . m . ~ ~ 8p ofPv compounds. The preparation and properties of cyclic oxyphosphoranes have been reviewed.37The 31Pchemical shift decreases with increase in the number of rings and with the replacement of P-0 bonds by P-C (aliphatic) bonds. These effects can eventually lead to negative values, e.g. 8p is - 11.7 p.p.m. for the phosphorane (21; X = CF,). Similar trends appear to occur in the phosphazocompounds (22).38The chemical shifts of cyclic oxyphosphoranes derived from hexafluoroacetone have also been compared with those of the PIII compounds from which they are prepared.39
+
X, Y,P-NR 0 -PE
t,
I I
RN-PY,
+
SP ofPvl compounds. The chemical shift of the pyridine adduct (23) is 82 p.p.m., The value of SP was found compared to SP of 29.8 for the original Pv to depend on the pyridine concentration in accordance with a rapid equilibrium between the Pv and Pvl forms. The high-field shift for (24), which was attributed to its Pvl structure, was supported by X-ray diffraction data.41
+
(23)
Fluorine-19. Fluorine chemical shifts have been considered to be of limited significance in the quest for Pvl However, the appearance of only one 3*
35
36 37 38
39 40 41
42
N. A. Makarova, E. T. Mukmenev, and B. A. Arbuzov, Bull. Acad. Sci. U.S.S.R., 1974, 23, 1769. M. A. Pudovik, 0. S. Shalyudina, L. K. Ivanova, S. A. Terent'eva, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 482. D. G . Gorenstein, J. Amer. Chem. SOC.,1975, 97, 898. B. A. Arbuzov and N. A. Polezhaeva, Russ. Chem. Rev., 1974, 43,414. H. A. Klein and H. P. Latscha, Z . anorg. Chem., 1974,406, 214; A. Schmidpeter and J. Luber, Phosphorus, 1974, 5, 55. E. E. Tsoliz, F. Ramirez, J. F. Mat, and C. P. Smith, Phosphorus, 19'74, 4, 109. F. Ramirez, V. A. V. Prasad, and J. F. Marecek, J . Amer. Chem. Soc., 1974, 96, 7269. K. P. John, R. Schmutzler, and W. S. Sheldrick, J.C.S. Dalton, 1974, 1841. J. Grosse and R. Schmutzler, Phosphorus, 1974, 4, 49.
Physical Methods
233
fluorine resonance for trifluorodimethylphosphorane and the dependence of the spectrum on solvent, concentration, and temperature have been interpreted in terms of an equilibrium involving the Pvl state (25). Electron-pair repulsion considerations suggest that there is a correspondence in bond properties between the basal fluorine
atom in a square-pyramidal molecule and the apical bonds in a t . b . ~ As . ~ a~ consequence, 8~ of the basal fluorine atoms should appear downfield of the apical fluorine atom for square-pyramidal molecules. Hence the relative chemical shift 8FCFC13 of +70.4 p.p.m. for the spirophosphorane (26) is not at variance with the X-ray structure (see page 261). The 19F chemical shifts of the iminophosphoranes (27) depend linearly on LJQof the P-aryl sub~tituents.~~ The insulating influence of the phosphonium atom is considerable. Calculations indicate that P-substituents may influence the mesomeric interaction between the phosphorus atom and an aryl group whilst maintaining the barrier to conjugation through the phosphorus atom.46 Carbon-12.The selective population-transfertechnique used in 13CFourier-transform spectroscopy has the advantages of being sensitive due to short acquisition times. It has been used for the determination of the assignment and relative signs of longrange couplings in compounds such as (28).4sThe assignment of 13Cn.m.r. signals of alkylaromatic compounds, such as tri(m-tolyl)phosphine, has been accomplished by selective proton irradiati~n.~'The known axial predominance of the P-methyl,
P-ethyl, and P-aryl groups in the phosphorinans (29) is manifest by C(3), C(5)signals at slightly higher field than in the t-butyl and isopropyl compounds, which have the equatorial c ~ n f o r m a t i o nThe . ~ ~ sulphides (30) exhibit greater shielding at C(3) and 43
44 45 46
47
4*
R,R. Holmes, J. Amer. Chem. SOC.,1974, 96, 4143. N, N. Zhmurova, V. G. Yurchenko, R. I. Yurchenko, E. V. Konovalov, and Yu. P. Egorov, J . Gen. Chem. (U.S.S.R.), 1974, 44, 2375. M. I. Kabachnik, Phosphorus, 1974, 4, 247. S. Soerensen, R. S. Hansen, and H. J. Jakobsen, J. Magn. Resonance, 1974, 14, 243. S. Soerensen, M. Hansen, and H. J. Jakobsen, J . Magn. Resonance, 1973, 12, 340. S. I. Featherman, S. 0. Lee, and L. D. Quin, J. Org. Chem., 1974, 39, 2899.
234
Organophosphorus Chemistry
C(5) by an axial sulphur than by an axial methyl group. It has also been noted that
SP is more upfield when steric compression is larger. The 13Cn.m.r. spectra of nonstabilized triphenylphosphonium ylides (3 1) show that the ylidic carbon is shielded It is considered that the shielding is relative to the correspondingphosphonium probably due to high electron density on the ylidic carbon atom. This effect was not observed for the stabilized ylides30fwhere the electron density on the a-carbon atom is less.5oThe 13Cn.m.r. spectra of the bisphosphonates such as (32) vary with concentration, owing to intramolecular effects of neighbouring P-0 bonds which alter 2 J ~ ~ . 5 1 Hydrogen-1. The lH chemical shifts of PII1 and As111compounds (33) are very close. The shifts are quite different for the corresponding four-co-ordinate compounds.62 The cis- and trans- mixture of phosphanols (34) was readily analysed by wellseparated methyl signals.63The parameters and assignments for the 106 theoretical
0
R Me,MY, -n (33)
Me
(34)
(35)
Me
(3-7)
transitions for triphenylphosphine have been dete~mined.~~ The lH n.m.r. spectra of the dioxaphosphorinans (35;R = Me, Pri, or Ph) show that there is a striking axial preference by the less electronegative P-sub~tituents.~~ This has been attributed to optimization of vicinal interactions about the P-0 bonds of the ring. When R is t-butyl, 1,3-syn interactions become dominant. The P-aryl electronic interactions in triarylphosphines and their PIv derivatives have been studied by lH n.m.r. The data were interpreted in terms of substituent additivity constants and Hammett substituent parameter^.^^ The methyl signal of the phosphorinone (36) has been used to study its c~nformation.~' With the aid of deuterium substitution and 31Pdecoupling 4Q
5O
51 52
53 54
55 56 57
T. A. Albright, W. J. Freeman, and E. E. Schweizer, J. Amer. Chem. SOC.,1975, 97, 940. B. Klabuhn, Tetrahedron, 1974,30,2327; J. M. F. van Dijk and H. M. Buck, Rec. Trau. chim., 1974, 93, 155. M. Fild and W. Althoff, J.C.S. Chem. Comm., 1973, 933. M. Durand, J. P. Laurent, and P. Lepage, J. Chim. phys., 1974, 71, 847. L. D. Quin and R. C. Stocks, J . Org. Chem., 1974, 39, 1339. S. Soerensen and H. J. Jakobsen, Acta Chem. Scand. ( A ) , 1974, 28, 249; L. Radics, E. BaitzGacs, and A. Neszmelyi, Org. Magn. Resonance, 1974, 6, 60. W. G. Bentrude, H. W. Tan, and K. C. Yee, J . Amer. Chem. SOC.,1975, 97, 573. R. Benassi, M. L. Schenetti, F. Taddei, and P. Vivarelli, J.C.S. Perkin ZZ, 1974, 1338. I. D. Blackburne, A. R. Katritzky, D. M. Read, R. Bodalski, and K. Pietrusiewicz, J.C.S. Perkin I I , 1974, 1 1 55.
Physical Methods
235
it was shown that the conformer shown as (36) is the most favoured form. The signals from those methyl groups of the phosphetan oxide (37) which are cis to the phenyl group are shifted upfield from 6 1.27 to 1.08 p.p.m.68Methyl signals have also been used to analyse heteropolymers derived from dimethyl methylpho~phonate.~~ Studies of Equilibria, Shift Reagents, and Solvent Effe~ts.-~lPN.m.r. spectroscopy is a very useful technique for following redistribution reactions. Studies have been reported on the exchange between MePCl, and MeP(OMe),,so on exchanges involving methylhalogenophosphinesand their corresponding chalcogenides,61on scrambling reactions involving tris(trimethylsilyl)phosphine,62 and on the interconversion of dialkyl phosphonates and chloro-phosphites.63 lH N.m.r. has been used to follow the redistribution of fluorine atoms and hydroxy-groups on phosphorus moieties in the formation of fluorophosphonic A study of the keto-enol tautomerism of some triphenylphosphoniumsalts revealed higher shielding of the phosphorus nucleus in the enol(38) than in the keto-form (39)65whereas the reverse applied to the cyclic oxides (40) and (41).66The diphenacyl-derivedylide (42)
Ph,kH=C
/OH
R' (3 8)
XP~$CH,COR
x-
(39)
gave temperature- and solvent-dependent spectra in the absence of protic impurities, indicating intra- or inter-molecular hydrogen exchange. Hydrogen bonding of phosphoryl compounds with phenol 68 and water has also been reported. The rate of intermolecular exchange between two PV compounds has been determined from intensity changes of IH and 31Pn.m.r. signals.'O R. E. Ardrey, J. Emsley, A. J. B. Robertson, and J. K. Williams, J.C.S. Dalton, 1973,23, 2641. R. A. Schep, J. H . J. Coetzee, and S. Norval, J. S. African Chem. Inst., 1974, 27, 63. 60 K. M. Abraham and J. R. Van Wazer, Inorg. Chem., 1974, 13,2346. 61 K. Moedritzer, Phosphorus, 1973, 2, 179; 1974, 4, 97. 62 H. Schumann, H. J. Kroth, and L. Roesch, 2.Naturforsch., 1974, 29b, 608. 63 0. N. Nuretdinova, Proc. Acad. Sci. U.S.S.R., 1974, 1365; 0. N. Nuretdinova, Dokludy Akad. Nauk S.S.S.R., 1974, 217, 1332. G4 R. Bender, C . Demay, J. C . Elkaim, and J. G . Riess, Phosphorus, 1974, 4, 183. 65 N. A. Nesmeyanov, S. T. Berman, P. V. Petrovskii, and V. I. Robas, Doklady Akad. Nauk S.S.S.R., 1975, 220, 1372. 66 W. R. Purdum and K. D. Berlin, J. Org. Chew., 1974, 39, 2904. 67 M. Jacquemart and M. H. Mebazaa, Compt. rend., 1974, 279, C, 655. 6 8 S. V. Zenin, M. Orban, and G . B. Sergeev, Magyar Kkm. Folyvdirut, 1974, 80, 432. 69 L. S. Bulyanitsa, G. P. Savoskina, and E. N. Sventitskii, Yud. Mugn. Rezon., 1974, 5 , 88. 70 F. Ramirez, S . Lee, P. Stern, I. Ugi, and P. D. Gillespie, Phosphorus, 1974, 4, 21.
58
59
236
Organophosphorus Chemistry
A study of the interaction of lanthanide shift reagents with a wide range of organophosphorus compounds revealed that Yb(fod), and Pr(fod), caused the maximum lH and 31Pshifts with minimum line broadening. 71 A pseudo-contact-shift mechanism accounts for most of the lH shifts; however, significant contact-shift contributions were required to account for most of the 31Pshifts. LIS values for the a- and &protons of the oxide (43) were obtained from the spectrum obtained by expanding with E ~ ( d p m ) , .A~ ~study of the ester (44) showed that europium and
(43)
(44)
(45)
praseodymium reagents form stronger bonds to the phosphorus ester group than to the carbon ester group.73 The identification of the diester (45) was aided by the expansion of the 13Cn.m.r. spectrum with uranium and europium shift Conformational analysis of adenosine and cytidine monophosphates has been reported, using a combination of shift probes and relaxation-time studies. 76 The structure of a phosphomannan has been investigated by 13Cn.m.r. with the aid of europium and praseodymium shift reagents.76Assignments were made on the basis of a parallel study on related mannose phosphates. The conformation of cyclic j3adenosine 3’,5’-phosphate in solution has been shown to be similar to that in the crystal by praseodymium and holmium shift studies on the lH n.m.r. Assignment of the n.m.r. signals of eight spirophosphoranes (46) was achieved using an europium shift reagent.78In some cases the reagent also displaced the phosphitephosphorane equilibrium. Pseudorotation.-The dynamic stereochemistry of pentaco-ordinated phosphorus compounds has been reviewed. 7 9 Variable-temperature spectra of the spirophosphorane (47; R = naphthyl) indicate that pseudorotation occurs only at elevated temperatures.80 A study of the spirophosphorane (47; R = o-isopropylphenyl)*l showed that raising the temperature above 33 “C caused the four ‘aryl’ 71
72
73 74
75
76 77 78
79
81
F. S. Manel, R. H. Cox, and R. C. Taylor, J. Magn. Resonance, 1974, 14, 235. R. B. Wetzel and G . L. Kenyon, J. Amer. Chem. SOC.,1974, 96, 5189. N. K. Davidenko, V. A. Bidzilya, A. G. Goryushko, V. A. Shokol, and K. B. Yatsimirskii, Teor. i eksp. Khim., 1974, 10, 500. G. Haegele, 2.Naturforsch., 1973, 28b, 753. C. D. Barry, C. M. Dobson, R. J. P. Williams, and A. V. Xavier, J.C.S. Dalton, 1974, 1765; C . D. Barry, D. R. Martin, R. J. P. Williams, and A. V. Xavier, J. Mol. Biol.,1974, 84, 491; C. D. Barry, J. A. Glasel, and R. J. P. Williams, J. Mol. Biol.,1974, 84, 471. P. A. J. Gorin and M. Mazurek, Canad. J. Chem., 1974, 52, 3070. D . K. Lavallee and A. H. Zeltmann, J. Amer. Chem. Soc., 1974,96, 5552. D . Hoalla, M. Sanchez, R. Wolf, M. Bois, D. Gagnaire, and J. B. Robert, Org. Magn. Resonance, 1974, 6,340. R. Luckenbach, ‘Dynamic Stereochemistry of Pentaco-ordinated Phosphorus and Related Elements’, Thieme, Stuttgart, 1973. D. Hellwinkel and W. Lindner, Chem. Ber., 1974, 107, 1428. G. M. Whitesides, M. Eisenhut, and W. M. Bunting, J. Amer. Chem. Soc., 1974, 96, 5398.
Physical Methods
237
methyl signals to coalesce to a single averaged line and caused the ‘isopropyl’methyl pair of doublets to coalesce to a doublet. Thus any pseudorotation process that leaves the chirality at phosphorus unchanged can be discarded. The data suggest that pseudorotation of this molecule does not occur by a single Berry process but rather by a mechanism involving a square-pyramidalintermediate with associated rotation of the isopropylphenyl group about the C-P bond. The existing n.m.r. data on spirophosphoranes such as (48) are consistent with the square-pyramidal structures shown to be the preferred conformation in the The accuracy and limitations of the estimation of apicophilicities and pseudorotational barriers from n.m.r. coalescence data have been discussed.83 The relatively high barriers to pseudorotation of spirophosphoranes such as (49; X = CF3) indicate that the turnstile rotation TR2 route, which by-passes the high-energy t.b.p. intermediate with a diradial ring, does not occur. The case for turnstile rotation is based on the low barriers (d5 kcal mol-l) to pseudorotation by adamantoid oxyphosphoranes (50) and on the premise
that the adamantoid structure is sufficientlyrigid to prevent the opposing movement of the apical and radial adamantoid oxygen atoms as required by the Berry mechanism.84In the case of difluoro-cyclic phosphoranes such as (5) there are two alternative high-energy t.b.p. intermediates, one with the ring diradial and the other with two fluorine atoms diradial. At - 80 “C the l9Fspectrum corresponded to two AB portions of two ABX spectra.85Such spectra could arise from the equilibriated pairs (51a), (51b) and (52a), (52b), provided that, in each pair, one form predominates. At 82
S3 84 85
R. R. Holmes, J. Amer. Chem. SOC.,1974, 96,4143. S. Bone, S. Trippett, and P. J. Whittle, J.C.S. Perkin I , 1974, 2125. F. Ramirez, I. Ugi, F. Lin, S. Pfohl, P. Hoffman, and D. Marquarding, Tetrahedron, 1974,30, 371; F. Ramirez and I. Ugi, Bull. Soc. chim.France, 1974, 453. D. B. Denney, D. Z. Denney, and Y. F. Hsu, Phosphorus, 1974, 4,213.
238
Organophosphorus Chemistry
- 40 "C an AB spectrum was observed which could only arise by interconversion via (53). Had the ring adopted a diradial disposition, the two fluorine atoms would have become equivalent. Thus the element effect between oxygen and fluorine is not strong enough to overcome the strain effect, as it does with the carbocyclic compound (54).86 The variable-temperature spectra of the tetrafluorophosphoranes (59, in combination with previously published data, indicate that the relative rates of pseudorotation increase in the order Y ,Me,N < SR, M < C1< Me, F.87The lineshapes of the central three lines of the 31Pn.m.r. spectrum contain sufficient information to distinguish between Berry and non-Berry permutations. Berry permutation between (56) and (57) interchanges aaBB and BBacx magnetic environments, and results in the transfer of magnetization between transitions 6 and 11 in Figure 1, and does not
-
Berry non-Berry
Figure 1
involve lines 7-10. Non-Berry permutation which occurs via (58) is the reverse. Hence lines 6 and 11 should broaden and coalesce when exchange is of the Berry type but all three central lines 6 , 7-10, and 11 should broaden and coalesce for a nonBerry type. The lack of broadening of the central line shows that the exchange is a Berry process. A new theoretical procedure has been developed which permits the calculation of the influence of an intermediate that is present in low concentration 87
N. J. Death, D. Z. Denney, D. B. Denney, and C . D. Hall, Phosphorcw, 1974, 3, 205. M. Eisenhut, H. L. Mitchell, D. D. Traficante, R. J. Kaufman, J. M. Dentch, and G . M. Whitesides, J. Amer. Chem. SOC.,1974, 96, 5385.
Physical Methods
239
along the pseudorotation co-ordinate. Application of this procedure to the spectrum of (55; Y = NMe,) indicated that, even if there was a square-pyramidal intermediate, it would not be possible to detect it by lineshape analysis at presently accessible spectral resolution. Computed and observed spectra of (59; Y = H)
coincided by assembling a probability matrix such that a radial fluorine ligand had an equal chance of exchanging with either of the apical fluorine ligands.88CND0/2 calculations on PF5 also favoured a Berry pseudorotation mechanism, and showed that the turnstile process corresponds to a special realization of rearrangement pathways in that reaction valley.89 Non-equivalence, Restricted Rotation, Inversion, and Configuration.-The lowtemperature lH and 13C n.m.r. spectra of the diphosphine (60) show two distinct environments for the t-butyl groups whereas the 31Pspectrum shows only one type of phosphorus atom.90The free energy of activation is ca. 12 kcal mol-1 for the process
(60) 88 89
QO
J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1974, 15. P. Russegger and J. Brickmann, Chem. Phys. Letters, 1975, 30, 276. S. Aime, R. K. Harris, E. M. McVicker, and M. Fild, J.C.S. Chem. Comm., 1974, 426.
240
Organophosphorus Chemistry
which averages the environments. The process is probably restricted rotation, with a preference for the gauche-conformer shown in (60) rather than inversion at phosphorus, because the two t-butyl signals have equal intensity. Activation parameters for restricted PN rotation in aminophosphines (61) are dependent on solvent and of the bulk of the substituents attached to nitrogen and c o n c e n t r a f i ~ nA. ~decrease ~ an increase of the bulk of the phosphorus substituents each reduce the barrier to PN rotation. The slP chemical shifts and 3JPNCH do not support the idea that large differences in the ground-state geometry are responsible for the variations. The cisand trans-isomers arising from restricted rotation were observed in the spectra of the A variable-temperature 31Pn.m.r. study of the ylide (62), determined at 34.5 OC.gp aminotetrafluorophosphorane(55; Y = NPrZi)showed that C--N bond rotation is slower than pseudorotati~n.~~ Non-equivalence of the methyl groups and the apical fluorine atoms at - 110 "C indicated that the two isopropyl groups are differently orientated, one with the methyl groups close to an apical fluorine, the other with the methyl groups away from the other apical fluorine atom, as shown in (63). The 19F spectrum of the methylthiotetrafluorophosphorane (64)also shows separate signals for the apical fluorine atoms, in accordance with restricted P-S The nonequivalence of the diastereotopic methylene protons of the acylphosphine (65), and
Me
/
/Me
YCOP 'CH2Ph
the absence of restricted rotation about the P-C bond, confirmed that these compounds have a pyramidal config~ration.~~ The P-inversion parameters were in the range 11-23 kcal m o F , the higher values being obtained from compounds possessing an electron-donating group Y,i.e. when there is a weakening of PCO conjugation. Variable-temperature 31Pand 'H n.m.r. spectra of the diphosphine (66) indicate that it possesses a trans configuration and that its conformational mobility is less
91 92
93 94 95
S. Distefano, H. Goldwhite, and E. Mazzola, Org. Magn. Resonance, 1974, 6, 1 , H. Yoshida, H. Matsuura, T. Ogata, and S. Inokawa, Clzem. Letters, 1974, 1065. A. H. Cowley, R. W. Braun, and J. W. Gilje, J. Amer. Chem. SOC.,1975, 97, 434. R. B. Johannesen, S. C. Peake, and R. Schmutzler, Z . Naturforsch., 1974, 29b,699. R. G . Kostyanovskii and Yu. I. El'Natanov, Doklady Akad. Nauk S.S.S.R., 1974, 219, 137.
241
Physical Methods
than that of dimethylcyclohexane.OsNon-equivalent methylene protons and alkoxygroups have been reported for the phosphonate (67).97N.m.r. spectroscopy has also been used to identify the threo- and erythro-isomersof (68),g8to estimate the proportions of diastereoisomers of spirophosphoranes such as (68),0° and to follow their epimerization. Spin-Spin Coupling.-The INDOR technique has been applied to the analysis of sparingly soluble phosphorus polymers.1ooThe Overhauser effect has been used in configurational studies of the ylide (69).lo1
JPPand JPM.A sensitive and accurate n.m.r. double-resonance technique has been described for the determination of J x x f for AnAnfXX’ spin systems in which JAA’ is It ~has been applied to the measurement of zero and JXX’is much larger than J A X . ~ O ~JP ofP the diphosphines (70; R = Me or Ph) by monitoring either component of the N doublet in the A spectrum, and the position of the centre of X has been determined P the by conventional A{X} double-resonance experiments. The values of ~ J Pfor cyclic polyphosphines (71 ; R = Me) and (71 ; R = CF,) have been compared.lo3 It appears that eclipsing of the lone pairs of electrons favours large negative values ~ positive. ~ The variation of 2 Jfor~the~ and that a 1,3-cis arrangement makes 2 Jmore
Se
I1
RPHal,
Y,PTe
(74)
biphosphonate (72) from 5 to 0.5 Hz upon dilution explains the changes of the 13C n.m.r. spectrum with concentration.lo4Studies of the phosphinoylamines (73) showed JPNP to be positive ( 1 6 - 4 3 Hz).lo5This anomaly to Bents’ rule may be due to J. G. Morse and K. W. Morse, Inorg. Chem., 1975, 14, 565. G. M. Gavrilova, A. S. Atavin, and B. A. Trofimov, Bull. Acud. Sci. U.S.S.R., 1974,23,623. 98 Yu. Yu. Samitov, I. V. Konovalova, V. P. Kakurina, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 494. 99 D. Bernard and R. Burgada, Phosphorus, 1974, 3, 187. loo L. N. Mashlyakovskii, A. V. Dogadina, and B. I. Ionin, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1171. 101 R. Bausch, B. Bogdanovic, H. Dreeskamp, and J. B. Kostev, Annulen, 1974, 1625. lo2 W. MacFarlane and D. S. Rycroft, J.C.S. Faraday 11, 1974, 70, 377. 103 J. P. Albrand and J. B. Robert, J.C.S. Chem. Comm., 1974, 644. lo4 M. Fild and W. Althoff, J.C.S. Chem. Comm., 1973, 933. lo5 G. Haegele, R. K. Harris, M. I. M. Wazeer, and R. Keat, J.C.S. Dalton, 1974, 1985. 96
97
Organophosphorus Chemistry
242
differences in hybridization. The PP couplings of a variety of sulphides of diphosphinyl compounds have been Values reported for Jp29si of some silylphosphines are in the range 1 5 - 4 2 H z . An equation relating the coupling to substituent structures has been presented.le The PSe coupling constant of the dioxaphosphorinans (74) is 20-30 Hz larger when the selenium atom is equatorially oriented than when it is axial.lo6Further values of JPse and JPTe have been determined for a range of selenophosphoryl dihalides (75) lo' and tellurides (76; Y = Alk, NEt2, or OEt).lo8 JPF and JPN. The PF coupling constants of the two non-equivalent apical fluorine atoms in (64) differ appreciably (930 and 1088 Hz). One of the apical fluorine atoms was also more strongly coupled to the methyl protons, but rather surprisingly it appeared as a quintet rather than the expected quartet. Computer simulation showed that the wavefunctionsof the radial fluorinesand hence of the entire molecule occur in two non-interacting sets which are symmetric and antisymmetric with respect to the plane of the molecule. Each of these functions leads to a quartet for one of the apical fluorine atoms, and it is accidental that the two quartets are so displaced as to give the appearance of a quintet. The spectrum of the phosphorane (77) was consistent with the presence of one apical CF, group but it had the unusually low PCF coupling constant of ca. 50 Hz.lo9The reduced P16Ncoupling constant (which takes
C1 (7 7)
(78)
(79)
(80)
into account the negative magnetogyric ratio of the 15Nnucleus) changed from negative to positive when the co-ordination number of the phosphorus atom was increased from PIII, as in (78), to PIv and PV, as in (79) and (80), respectively.l1° The same changes have been observed for direct bond PC and PP couplings. Qualitatively, the sign changes and magnitudes relate to the changes in hybridization of the phosphorus bonding orbitals, being nearly zero s-character for the PII1atom (KPNis - 106.7 Hz), approximately 25 s-character for the PIv atom (KPNis 107.5 Hz), and having 33 % s-character for the radial bonds of the Pv atom (KPNis + 165.3 Hz). The P14N coupling constant for the isocyanide (17; Y = NC) was found to be very much smaller in magnitude (13.9 H z ) . ~ ~ JPC. Direct bond coupling of a PII1 atom to an aliphatic carbon, which is usually negative (- 10 to -44 Hz), is dependent on ring size, and for the phosphetan (81) ~ J PisCvery small but negative.lll The ~ J P C involving the phenyl ring remains negative but is of greater magnitude. This is now seen to be a consequence of the
+
lo6W.
J. Stec, Z . Nuturforsch., 1974, 29b, 109.
H.Roesky and W. Kloker, 2. Natrrrforsch., 1973, 28b,697. I. A. Nuretdinov and E. I. Loginova, Bull. Acad. Sci. U.S.S.R., 1973, 22, 2765. D.D. Poulin and R. G. Cavell, Inorg. Chem., 1974, 13, 2324.
lo7 lo8
1°9 110
J. R. Schweiger, A. H. Cowley, E. A. Cohen, P. A. Kroon, and S. L. Manatt, J. Amer. Chem. SOC.,1974, 96,7122. ll1 G. A. Gray and S. E. Cremer, J.C.S. Chem. Comm., 1974, 451.
Physical Methods
243
0
ll
Y,PC=CR
CHMe, I
change in bond angles, which causes a redistribution of s-character. The PC coupling constants of the phosphorane (82) are ~ J P(apical) C 7.3 Hz, ~ J P(radial) C 116 Hz, which gives a remarkably good correlation with s-character, taking 56 Hz as the coupling constant for compounds with sp 3-hybridized phosphorus bonding orbitals.l12This also suggests that (82) deviates little from t.b.p. stereochemistry. The larger variation of lJpc for ylides such as (31) compared to the correspondingsalts is attributed to larger changes in hybridization of the or-carbon atom when it bears a lone pair of electron^.^^ The two-bond PCC coupling within the ring of the phosphorinans (83) is smaller (3-3.5 Hz) for the methyl, ethyl, and phenyl derivatives, which have the conformation shown, relative to the t-butyl and isopropyl com.~~ to pounds (6-7 Hz), which have the alkyl group equatorially ~ r i e n t a t e dCouplings acetyleniccarbons are positive for ~ J Pand C 2 Jof ~ the oxides ~ (84).l13 They are larger than those reported for saturated and aromatic phosphine oxides. The coupling constants of the acetylenic phosphines are normal. The conformational preferences of the dioxaphosphorinans (6) l 8 and (85) 114 have been estimated from PC coupling constants. The low-temperature spectra of the aminophosphine (86) showed that 'JPNCC is not the same for all four methyl groups.115The large coupling (23 Hz) for one of the methyl groups, compared to the small couplings (6,4, and > 2 Hz) for the other three, could result from a through-space contribution. The corresponding sulphides did not exhibit this difference,all 3 J p values ~ being in the range 19-24 Hz. JPH and JPC,H. The direct PH coupling constants of a number of protonated phosphites (87) and the corresponding acids, e.g. (88), are of nearly twice the magnitude
112 113
114 115
H. Schmidbaur, W. Buchner, and F. H. Koehler, J. Amer. Chem. SOC.,1974, 96, 6208. R. M. Lequan, M. J. Pouet, and M. P. Simonnin, J.C.S. Chem. Comm., 1974, 475. A. A. Borisenko and N. M. Sergeev, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2733. J. Burdon. J. C. Hotchkiss. and W. B. Jennings, Tetrahedron Letters, 1973, 4919.
Organophosphorus Chemistry
244
Ph, P(CH,CH-==CH)3-,I
of ~JPH of protonated phosphines.l16The magnitude increases (a) as OH groups replace 0-alkyl groups,25(6) as 0-alkyl is replaced by OPh, and (c) as 0-alkyl groups are constrained in a cyclic systern.llsThe PH coupling constants of dioxaphosphorins isH always larger when the also vary markedly with conformational changes, and ~ J P hydrogen is equatorial, as shown in (89).106v117Small differences are found in the diastereomers of the secondary phosphine (90).l2 The geminal PCH coupling constant is very small (< 0.8 Hz) for the alkenylphenylphosphines(91).11*It is very much larger for the corresponding oxides, whereas 3JPH is little changed between the PII1 and PIv compounds. The PCH coupling is 6-7 Hz in cyclic phosphine oxides (92) l ~ ~ geminal than vicinal coupling when the proton is trans to the P=O g r 0 ~ p .Smaller constants, as in the quasi-phosphonium salts (93) lZoand vinylphosphonates (94),121 Me
X-
H
(P~o),~H,cH,R
OH ‘CH2F’h
0
II
(EtO),PCH=-CHR
0
II
(RO),P-CHCN
I
HCRCN
PhnMe,-,P==CH,
are not unusual; however, in the phosphonates (95) the reverse applies.122The geminal coupling constants for the ylides (96) vary little as methyl groups replace phenyl g r 0 ~ p s . The l ~ ~large vicinal coupling constant (28 Hz) observed for the oxide (43) is probably a result of the 180”dihedral angle.72 The magnitude and relative signs of the coupling constants of triphenylphosphine have been dete~mined.~~ The HH couplings were nearly the same as those found in benzene. Studies of derivatives of L. J. Van de Griend and J. G . Verkade, Phosphorus, 1973, 3, 13. R. D. Bertrand, H. J. Berwin, G. K. McEwen, and J. G. Verkade, Phosphorus, 1974, 4, 81. P. W. Clark, J. L. S. Curtis, and P. E. Garrou, Cannd. J. Chem., 1974, 52, 1714. D. M. Washecheck, D. Van der Helm, W. R. Purdumm, and K. D. Berlin, J . Org. Chem., 1974, 39, 3305. 120 H. R. Hudson, R. G . Rees, and J. E. Weekes, J.C.S. Perkin I , 1974, 982. 121 D. Gloyna, H. Koeppel, and H. G. Henning, J. prakt. Chem., 1974, 316, 832. 122 D. Danion and R. Carrie, Bull. Soc. chim. France, 1974, 1538. 123 H. Schmidbaur and M. Heimann, Z . Naturforsch., 1974, 29b, 455. 116
117 118 119
Physical Methods
245
triphenylphosphinehave been r e ~ o r t e d , ~ 124~and g they also indicate that there is only a small interaction of the PII1atom with the aryl rings. EHMO calculations support the generally accepted explanation that the coupling constants are dependent on the s-character of the bonding orbitals of phosphorus and on the orientation of the phosphorus lone pair of e1ectr0ns.l~~ The four-bond couplings of the ally1 compounds (97) were found to be negative (- 3.4 to - 8.5 H z ) , and ~ ~ ~for the diphos~ ~ ~ coupling constants have also been phonate (98) they are 3.5-4.05 H z . Long-range reported for the methyl derivatives of (99)12’ and for the sulphide
JPC,XH and JPXCH.The stereospecific PCCOH coupling of the phosphonate (101) is positive (+3.8 Hz in DMSO and +3.1 Hz in acetone).129Further conformational studies of dioxapho~phorinans,~~~ p h o ~ p h o l a n s and ,~~~ the P I V heterocycles (102) 13*
have been reported. There is a large difference between JPOCH of equatorial protons (29Hz) and axial protons (4Hz) of the sulphides (102; Ch = S).133It has been shown that the conformer with an axial sulphur atom is preferred in carbon tetrachloride solution whereas a mixture of conformers is evident in acetonitrile solutions. The traditional Karplus approach and the pseudorotational treatment of coupling constants were found to be comparable for the conformational analysis of AMP.134 124 125
126 127 128 129 l30 131 132 133 134
R. Benassi, M. L. Schenetti, F. Taddei, and P. Dembech, J.C.S. Perkin ZI, 1974, 1338. V. I. Lakharov, A. V. Dogadina, L. N. Mashlyakovskii, B. I. Ionin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 96. S. V. Kraglov, B. I. Ionin, and A. A. Petrov, J . Gen. Chem. (U.S.S.R.), 1974, 44, 2606. J. B. Levy, Israel J. Chem., 1974, 12, 779. D. W. Grisley and K. Szabo, jun., J. Chem. and Eng. Data, 1974, 19, 175. T.Bottin-Strzalko, M. J. Pouet, and M. P. Simonnin, Org. Magn. Resonance, 1974, 6, 419. B. A. Arbuzov, R. P. Arshinova, Yu. M. Mareev, I. Kh. Makirov, and V. S. Vinogradova, Bull. Acad. Sci. U.S.S.R., 1974, 23, 629. J. Devillers, M. Cornus, and J. Navech, Org. Magn. Resonance, 1974, 6, 21 1. J. F. Brault, J. P. Majoral, P. Savignac, and J. Navech, Bull. SOC.chim. France, 1973, 3149; J. P. Majoral, C. Bergounhou, and J. Navech, ibid., 1973, 3146. J. P. Dutasta, A. Grand, J. B. Robert, and M. Taieb, Tetrahedron Letters, 1974, 2659. F. E. Evans and R. H. Sarma, J . Biol. Chem., 1974,249, 4754.
9
246
0rganophosphorus Chemistry
Analysis of J P O C H values of the enolphosphates (103) revealed the presence of planar and gauche conformations, except when Y was a bulky group.135A wide range of PCNH coupling constants has been reported for the oxazaphospholidines. For example, JPNCEI is 28.1 and 0.9 Hz for (104).136 Only small differences were observed for the JPSCH values of (105).13’ Relaxation Times, Paramagnetic Effects,and N.Q.R. Studies.-lT Relaxation times Chemically have been found to be useful for the study of phosphatidyl~holines.~~~ induced dynamic nuclear polarization has been used in the study of ABN-initiated oxidation of triethyl phosphite and triethyl p h 0 ~ p h a t e . lN.q.r. ~ ~ spectra of alkoxysubstituted PII1compounds have been determined.l*O The P-C1 bond character of PlrI and P I V compounds has been estimated by n.q.r.141 The generality of the relationship between P-CI bond length and PCl, bond angles on the one hand, and 35C1 n.q.r. frequencies on the other, suggests the absence of significant differences in the electronic nature of the P-CI bond of PII1 and PIv The 35Cl
frequencies of the dichlorides (106) depend on the nature of the aryl The sulphides (106; Ch = S) gave resonances 0.1-1.0 MHz larger than those of the oxides. The pseudorotation of the chlorophosphoranes (107) and (108) has been studied by variable-temperature n.q.r. Reports have also appeared on the iminophosphorane (109).144 E. M. Gaydou and J. R. Llinas, Org. Magn. Resonance, 1974, 6, 23. J. Devillers, M. Cornus, J. Roussel, J. Navech, and R. Burgada, Org. Magn. Resonance, 1974,6, 205; J. Devillers, J. Roussel, and J. Navech, ibid., 1973, 5, 511. 137 M. Baudler, K. Glinka, U. Kelsch, H. Sandmann, and W. Heller, Phosphorus, 1972, 2, 161. 138 B. A. Cornell, J. M. Pope, and G. J. F. Troup, Chem. andPhys. Lipids, 1974,13,183; B. Sears, W. C. Hutton, and T. E. Thompson, Biochem. Biophys. Res. Comm., 1974,60,1141; B. Sears, J . Membrane Biol., 1975, 20, 59. 139 D. G. Pobedimskii, V. A. Kurbatov, I. D . Temyachev, Yu. Yu. Samitov, and P. A. Kirpichnikov, Teor. i eksp. Khim., 1974, 10, 492. 1.10 I. P. Biryukov, Izvest. Leningrad Elektrotekh. Iiist., 1974, NO. 141, p. 28. 111 V. E.Bel’skii, V. A. Naumov, and I. A. Nuretdinov, Proc. Acad. Sci. U.S.S.R., 1974,215,260. 143 1. P. Biryukov and A. Deics, Latu. P.S.R. Zinat. Akad. Vestis, Kim. Ser., 1974, 493. 143 V. A. Mokeeva, I. V. Izmest’ev, I. V. Kyuntsel, and G . B. Soifer, Fiz. Tverd. Tela, 1974, 16, 1714. 14-1 V. A. Mokeeva, I. V. Izmest’ev, I. A. Kyuntsel, and G. B. Soifer, Fiz. Tverd. Tela, 1974, 16, 3649; Pis’ma, Zhur. eksp. teor. Fiz., 1974, 19, 580. 135
Physical Methods
247
2 Electron Spin Resonance Spectroscopy The e.s.r. spectrum of the phosphabenzene radical anion (110) is characterized by a dominant splitting by The spin distribution corresponds to that of a planar cyclic n system. The coupling constants at C-3, -6, and -7 of the 2-phosphanaphthalene radical anion (111) are similar to those in naphthalene and isoquinoline.14sThere have been several studies of two-co-ordinate phosphino radicals (112).
The 31P isotropic coupling constants are in the range 72-97 G, which indicates a high spin density on phosphorus and therefore little tendency for the odd electron to delocalize onto the phosphorus ligands.l*' The diphenylphosphino radical (1 12; Y = Ph) has been prepared by the U.V. irradiation of triphenylpho~phinel~~ and by that the odd electron is in an almost a variety of other It was purep-orbital and therefore that the lone pair of electrons is coplanar with the CPC plane. The spectrum of the diaminophosphino radical (112; Y = NHPh) has been recorded and compared with that of (1 12; Y = Ph).150Further study of the radicals formed by the y-irradiation of trimethyl phosphite has confirmed the dimeric nature of the radical cation (113), which possesses two anisotropically equivalent phosphorus atoms.161The e.s.r. spectra of phosphoranyl radicals (generated by addition of photolytically produced alkoxyl radicals to alkoxyalkylphosphines)correspond to the t.b.p. structures predicted to be the thermodynamically most stable on the basis of the greater apicophilicity of alkoxy-groups relative to alkyl The studies also indicate that a-scission is fastest when this initial phosphoranyl radical has an apical ethyl group, e.g. as in (114). Thus there is preferential departure of alkyl groups from the apical sites. In contrast, the normal apicophilic trends of the ligands of most phosphoranyl radicals and PV compounds appear to be reversed for phosphoranyl radicals which possess four strongly electronegative phosphorus ligands, The hyperfine interactions and such as fluorine and the trifluoromethoxy-group.153 the preferred stereochemistry deduced for such a radical are shown in (115), since the
F. Gerson, G. Plattner, A. J. Ashe, and G. Markl, Mol. Ph,ys., 1974, 28, 601. C. Jongsma, H. G. De Graff, and F. Bickelhaupt, Tetrahedron Letters, 1974, 1267. B. W. Fullam, S. P. Mishra, and M. C. R. Symons, J.C.S. Dalton, 1974, 2145. 148 W. T. Cook, J. S. Vincent, I. Bernal, and F. Ramirez, J. Chem. Phys., 1974, 61,3479. 149 M. Geoffroy, E. A. C. Lucken, and C. Mazeling, Mol. Phys., 1974, 28, 839. 150 L. Ginet and M. Geoffroy, Helv. Chim. Acta, 1974, 57, 1761. 151 T. Gillbro, C. M. L. Kerr, and F. Williams, MoZ. Phys., 1974, 28, 1225. 152 A. G. Davies, R. W. Dennis, and B. P. Roberts, J.C.S. Perkin ZI, 1974, 1101. lS3 A. J. Colussi, J. R. Morton, and K. F. Preston, J. Phys. Chem., 1975, 79, 651. 145 146 147
9*
Organophosphorus Chemistry
248
hyperfine interactions have the same trends as in the radical (116). Similar parameters have been obtained for the corresponding tris(trifluoromethy1)rnethoxy derivative of (1 15). When the alkoxy-group chosen was the less electronegative t-butoxy-group, the e.s.r. parameters corresponded to the normal stereochemistry shown in (117). In support of these conclusions, INDO calculations on the PF4 radical indicated that the radial fluorine atoms possess the larger electron density. The phosphoranyl radicals containing PH bonds are quite stable, and the e.s.r. spectrum of (1 16) can be obtained at + 40 "C.E.s.r. studies indicate that the addition of hydrogen atoms to dimethyl hydrogenphosphonate gives the radical (1 18), which is kinetically favoured as a result of apical attack, but that radicals such as (119) are
thermodynamically more ~ t a b 1 e . It l ~has ~ been suggested that the hydrogen ligaiid has greater mobility than an alkoxy-group. This is supported by the retention of configuration which occurs in the reaction of t-butoxyl radicals with cyclic ph0~phites.l~~ Studies of the phosphorus oxytrichloride radical anion indicate that the unpaired electron occupies a molecular orbital of a, symmetry which involves a modified apical orbital, and that this is probably the cause of the large isotropic hyperfine couplings for apical hydrogen l i g a n d ~ . lINDO ~ ~ calculations predict that there is a 18 pm difference between the apical and radial bond lengths of phosphoranyl The e.s.r. spectra of monophenylphosphoranyl radicals fall into two ranges, those with a(P) of 600-1009 G and those with a(P) of 9 4 5 G. The former correspond to molecules with t.b.p. stereochemistry as shown in (120), where Y is Cl, SMe, H, or OCH2CF2,and the latter correspond to tetrahedral stereochemistry with the odd electron delocalized in the benzene ring, as shown in (121), where Y is OMe, Y
OEt, or Ph.1589159 The latter compounds can be confidently assigned the tetrahedral stereochemistry because the spectrum of the pentadeuteriophenyl radical (121 ; Y = OEt) shows reduced coupling to the ring hydrogen atoms, and this confirms 15.1
lSG lss 1SY
M. C . R. Symons, Mol. Phys., 1974, 27, 785. H . W. Tan and W. G . Bentrude, J. Amer. Chem. Sor., 1974,96, 5950. T. Gillbro and F. Williams, J. Amer. Chem. SOC.,1974, 96, 5032. A. Hudson and J. T. Wiffen, Chem. Phys. Letters, 1974, 29, 113. A. G . Davies, M. J. Parrott, and B. P. Roberts, J.C.S. Chem. Comm., 1974, 973. G. Boekestein, E. H. J. M. Jansen, and H. M. Buck, J.C.S. Chem. Comm., 1974, 118.
Physical Methods
249
‘1,
(HO),P
kH
that a(P) is equal to a(para-H) in the corresponding protic r a d i ~ a 1 . lTetrahedral ~~ structures were also allocated to the tri-co-ordinated radicals (122; Y = Me or OMe).15@ The e.s.r. spectra of further examples of tetrahedral biphenylenephosphorany1 radicals (123) have been reported.lsoThe lH and 31Pcoupling constants of the radical cations (124) and (125) indicate that there is little delocalization of the unpaired electron to the phosphorus atom,lel cf. the triphenylphosphoniummethylene The hyperfine splitting constants to the ortho-protons of radicals produced by the electrochemicalreduction of the phosphinobenzoates(126) and their
oxides indicate that both the PI11 and PIV groups have electron-accepting properties.lS2meta-Orientated groups have little effect on spin densities. The iminophosphorane radical (127)la3and the nitroso-radicals (128) and (129)lS4have been identified by e.s.r. spectroscopy. The latter radicals were prepared by addition of nitrosobenzene to vinyltriphenylphosphoniumbromide. Spin-labelledphosphonates such as (130) were prepared by the reaction of the hydroxy-function of the nitroxyl radical with the appropriate phosphonyl halide.lS5Splittings, which depended on the R. Rothuis, J. J. H. M. Font Freide, J. M. F. van Dijk, and H. M. Buck, Rec. Trav. chim., 1974, 93, 128. 161 M. Geoffroy, L. Ginet, and E. A. C. Lucken, Mol. Phys., 1974,28, 1289. 1 6 2 A. I. Prokof‘ev, S. P. Solofovnikov, I. G . Malakhova, E. N. Tsvetkov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2601. 163 H. B. Stegmann, K. Scheffler, G. Bauer, R. Grimm, S. Hieke, and D. Sturner, Phosphorus, 1974, 4, 165. 164 R. K. Howe and P. A. Berger, J . Org. Chem., 1974, 39, 3498. 165 G. Sosnovsky and M. Konieczny, 2.Naturforsch., 1973, 28b, 488. 160
0rganophosphorus Chemistry
250
number of nitroxyl radicals introduced into the molecule, confirmed the structures. Nitroxide spin labels have been used to study the structure of phospholipids.16s Porphyrin complexes,167 methaemoglobin,168 lipoprotein-blood interactions,169 metal ion-GMP interactions,170and tcne complexes171have also been studied by e.s.r. spectroscopy. 3 Vibrational Spectroscopy A book entitled 'The Interpretation of I.R. Spectra of Organophosphorus Com-
pounds' has been p ~ b 1 i s h e d . lThe ~ ~ absorption frequency of the P-N bond in PrI1 compounds is generally in the range 7 9 0 - - 1 0 1 0 ~ m - ~ .Conversion ~~~ of the phosphorus atom to the PIV state would be expected to increase d,,-pn back-bonding; however, the PIV-N stretching frequency is usually found below lo00 cm-1;31bp 17* indeed v(P-N) of the azido-salts (12)24is assigned to bands at ca. 770 cm-l. Backbonding is expected to be maximal in iminophosphoranes, and it appears to exert its influence on the stretching frequency."e Thus the P=N stretching mode is assigned to the peak at 1152 cm-l in the spectrum of the tosylamine (131) 175 and to the composite band at 1190-1205 cm-1 in the spectrum of the PNP compounds (132).176 SMe
I
EtP=NSO&
I
H4Me
The v( P=O) frequencies recorded for phosphoryl compounds in ten different media indicate that dipole-dipole interactions depend on intermolecular effects of the P-substituents and that the interaction increases with the dipole moment of the compounds.l 7 7 The phosphorus substituents of triarylphosphine chalcogenides have been found to have a smaller influence on v(P=O) than on v(P=S) or V ( P = S ~ ) . ~ ~ ~ The mechanisms of the changes in the phosphorus-chalcogenide bond order have been discussed. The bands in the far4.r. spectrum of triphenylphosphine oxide have B. J. Gaffney and H. M. McConnell, Chem. Phys. Letters, 1974, 24, 310. B. B. Wayiand and M. E. Abd-Elmageed, J.C.S. Chem. Comm., 1974, 61. 168 P. Hensley, S. J. Edelstein, D. C . Wharton, and Q. H. Gibson, J , Biol. Chem., 1975, 250, 952. 169 M . D. Barratt, A. R. Badley, R. B. Leslie, G . G . Morgan, and G . K. Radda, European J. Biachem., 1974, 48, 595. l i O S. K. Podder, S. K. Rengan, and R. Navalgand, J. Magn. Resonance, 1974, 15, 254. 171 V. V. Pen'kovskii, Yu. P. Egorov, R. I. Yurchenko, and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.), 1973,43,2618; F. Sersen, P. Banacky, and L. Krasnec, Cull. Czech. Chem. Comm., 1974, 39, 3224. 1 7 2 L. C. Thomas, 'Interpretation of the Infrared Spectra of Organophosphorus Compounds', Heydon, London, 1974. 173 R. Mathis, L. Lafaille, and R. Burgada, Spectrochim. Acta, 1974, 30A, 357. 1 7 ~E. 1. Matrosov, V. A. Gilyarov, V. Yu. Kovtun, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1971, 1076. 1 7 5 L. Almasi and R. Popescu, Chem. Ber., 1975, 108, 856. 176 R. M. Clipsham, J. D . Pulfer, and M. A. Whitehead, Phosphorus, 1974, 3, 235. 177 R. R. Shagidullin, V. E. Bel'skii, L. Kh. Ashrafullina, L. A. Kudryavtseva, and B. E. Ivanov, Bull. Acad. Sci. U.S.S.R.,1973, 22, 2442. 158 R . F. De Ketelaere and G. P. Van der Kelen, J. Mol. Structure, 1974, 23, 233. lti6
167
Physical Methods
25 1
been 8s~igned.l’~ The v ( P 4 ) band of the alkyl- and aryl-thiophosphetan oxides (1 33 ;X = SR) occurs at 1194-1203 cm-l, exactly as predicted by the ChittendenThomas formula.68The assignments of v(PSC) and v(CPC) bands have been discussed. The changes of the P=O and P=S frequencies and force constants have been
(133)
(135)
recorded for the series (1 34).180 The A2- and A3-phospholens possess characteristic CH stretching frequencies.The olefinicproton of A2-phospholens(1 35) appears near 3065 cm-l and is shifted to near 3080 cm-l in dilute carbon tetrachloride solutions, suggesting that it is more acidic than the olefinic proton of A3-phospholens(136), which appears at 3050k 10 cm-l and which is unchanged upon dilution.lsl The PC stretching frequency of arylphosphonic acids (137 ; R = aryl) has been assigned to a band at 1150 cm-l.lal An appropriate band in the 1400 cm-l region was not observed. The CPC symmetric and asymmetric stretching frequencies for the phosphetan acids (133; X = OH) have been assigned to bands at 1165 and 1255 cm-l, respectively.la2The i.r. spectra of n-propyl- up to hexadecane-phosphonicacids (1 37)lS3and
those of some azobenzeneaminophosphonic acid diestersla4have been recorded and the band assignments and trends discussed. The vibrational spectra of the phosphines (138),lS6some hypophosphites and phosphinothioates,la6 phosphonates (44),73 cyclic oxypho~phoranes,~~~ lE7 and the phosphorane (82)lS8have also been analysed. StereochemicalAspects.-The vibrational spectra of the dioxaphospholan (139) and phosphorinan (140) down to - 160 “C supported the postulate of the presence of at least two conformers.189Rotational isomerism is frequently invoked to explain doubling of the P=O absorption.lgOHowever, there are several absorptions in the 179
S. Milicev, Spectrochim. Acta, 1974, 30A, 255.
180
D. Koettgen, H. Stoll, R. Pantzer, and J. Goubeau, 2.anorg. Chem., 1974, 405, 275. R. R. Shagidullin, A. V. Chernova, D. F. Fazliev, A. 0. Vizel, and V. K. Krupnov, Bull. Acad. Sci. U.S.S.R., 1974, 23, 1533; U. Dietze, J. prakt. Chem., 1974, 316, 485. J. Emsley, T. B. Middleton, and J. K. Williams, J.C.S. Dalton, 1974, 633. U. Dietze, J . prakt. Chem., 1974, 316, 293. V. Jagodic and L. Tusek, Croat. Chem. Acta, 1972, 44, 445. H.Schumann and L. Roesch, Chem. Ber., 1974,107, 854. B. Schaible, K. Roessel, J. Weidlein, and H. D. Hausen, 2.anorg. Chem., 1974, 409, 176. W.G. Bentrude, W. D. Johnson, and W. A. Khan, J. Amer. Chem. Soc., 1972,94,923. H.Schmidbaur and H. Stuehler, Chem. Ber., 1974,107, 1420. A. B. Remizov and D. F. Fazliev, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1167. E.V. Ryl’tzev, V. G . Koval, V. Ya. Semenii, and Yu. P. Egorov, Teor. i eksp. Khim, 1974,10,
181 182 183 184 185 186 187 lE8 189 l9*
637.
Organophosphorus Chemistry
252
n 0
0
‘P’
OMe
n
OLP/O OMe
bb I/
0
1150-1220 cm-l region of the spectra of the cyclic oxide (141), which cannot exist in more than one conformation. Evidence that the multiplicity is due to Fermi reso. ~ ~ most prominent peak in the l60 nance was obtained by l80i n c o r ~ o r a t i o nThe spectrum is the band at 1235 cm-l, which with l 8 0 incorporation is shifted and apparently brought into Fermi resonance as a doublet at 1228 and 1205 cm-l. There is another doublet at 1178 and 1212 cm-1 in the natural-abundance spectrum which is shifted to 1144 and 1170 cm-l in the l80spectrum. Similar spectra were obtained for the cyclic oxides (142) and (143). Triple Fermi resonance was postulated recentlylgl
and it has been considered t h e ~ r e t i c a l l y Conformational .~~~ analysis of the oxides (144; Y = CHzO; Z = Alk, Ph, or C1) by combined use of i.r. spectroscopy and dipole moments has been reported.lg3The effects of changing the dielectric permeability of the medium have been used in the conformational analysis of halogenomethylphosphine oxides (145; Hal = Br or l)lg4[monitoring the v(CHa1) and v(PC) bands], and in the conformational analysis of vinyl- and isopropenylphosphonic acid chlorides and esters (146; Ch = 0 or S)lo5 [monitoring the
0
II
0
II
v(C=C) doublets]. The doubling of the PCI bands has been used in a study of ethylphosphonyl and -phosphinyl chlorides (147).lg6The additional carbonyl band in the spectra of some acylphosphine oxides has been attributed to an impurity.lg7 No M. P. Lisitsa, N. E. Ralko, and A. M. Yaremko, Optika i Spektroskoyiya, 1970, 28, 235. J. Konarski, Phys. Letters ( A ) , 1971, 35,251. 193 0. A. Raevskii, J . Mol. Strircture, 1973, 19, 275. l94 0. A. Raevskii, A. N. Vereshchagin, Yu. A. Donskaya, F. G. Khalitov, and E. N. Tsvetkov, Bull. Acad. Sci. U.S.S.R., 1974, 23, 754. 195 A. B. Remizov, R. D. Gareev, and A. N. Pudovik, J. Gen. Cheni. (U.S.S.R.), 1974,44, 1831. 1 g 6 A. N. Pudovik, I. Ya. Kuramshin, A. B. Remizov, A. A. Muratova, and R. A. Manapov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 41. 197 B. N. Laskorin, V. V. Yakshin, and L. I. Sohal’skaya, J. Gen. C/iC?7?. (U.S.S.R.), 1974,44, 1685.
191 192
253
Physical Methods
evidence was obtained for restricted PC rotation in phenyldichlorophosphine or its chalcogenides from their variable-temperature i.r. spectra.lg8 Combined i.r. and dipole-moment studies of trichloromethylphosphonates(148) l g 9and dithioic esters (149) 2oo suggest preferences for gauche-oriented ester groups. A further investigation
of phosphonate and phosphate esters concludes that the most stable conformations have the largest number of gauche orientations and that the cis orientation of groups is the most favoured in phosphoryl compounds.201 It has also been suggested that the conformational composition is not a monotonic function of dielectric constant and that the strengths of the internal electric field in a liquid and the van de Waals interactions play important roles. The change in the integral ratios of the vs(PC12)bands (513 and 535 cm-l) of the amide (150) at 300-180 K indicated that electronwithdrawing groups on the aryl ring alter PN conjugation and produce a predominance of one conformation.202There were no conformational changes upon altering the dielectric constant or temperature. The vibrational spectra of some bisphosphine chalcogenides203 and of a chloro-anhydride204 have been interpreted. Studies of Bonding.-The i.r. spectra of some cyclic alkenyl-dichlorophosphinesand phosphonyl dichlorides such as (151) showed that v(C=C) and the intensity of the CH band were altered by conjugation of the double bond with the Pel2 group.2o5The intensities of the v8 ring-stretching band of arylphosphine chalcogenides have been used to estimate CJR' values of the phosphorus groupszo6and the v(NH) and v(P0) frequencies of the hydrazides (152) have been related to the rate constants of their
Ch
198 199 200
201 202
203 204
205 206
A. B. Remizov and I. Ya. Kuramshin, Zhur. priklad. Spektroskopii, 1974, 20, 324. E. A. Tshmaeva, F. M. Kharrasova, A. B. Remizov, and A. N. Pudovik, Proc. Acad. Sci. U.S.S.R., 1974, 218, 605. E. A. Ishmaeva, V. V. Ovchinnikov, R. A. Cherkasov, and A. B. Remizov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2582. V. I. Katolichenko, Yu. P. Egorov, Yu. Ya. Borovikov, and G. A. Golik, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2475. 0. A. Raevskii, Yu. A. Donskaya, and L. A. Antokhina, Bull. Acad. Sci. U.S.S.R.,1973, 22, 2438. R. C. Dobbie, M. J. Hopkinson, and B. P. Straughan, J. Mol. Structure, 1974, 23, 141. E. Payen and M. Migeon, Compt. rend., 1974, 279, C, 687. E. I. Babkina and V. A. Kozlov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2073. T. B. Grindley, K. F. Johnson, H. Kaack, A. R. Katritzky, G. P. Schiemenz, and R. D. Topsom, Austral. J. Chem., 1975, 28, 327.
Organophosphorus Chemistry
254
reaction with phenyl Also, vas (PF,) of difluorophosphoranes R3PF2 Hydrogen-bondis linearly related to the sum of the Taft inductive constants of R.42 ing is again a very popular area of study. The v(0H) frequencies of the hydrogenbonded species produced by hydroxymethylphosphonyl compounds have been divided into those corresponding to polymers, dimers, monomers solvated at the phosphoryl group, monomers solvated at the ester oxygen, and free monomers.2os The thermodynamic characteristics of the hydrogen bonds of the P=O group with water209and with decano1210have been estimated and the formation of an intermolecular bond between phenol and phosphoryl compounds (153) has been used as a standard reaction for the calculation of CT constants of the Y substituents.211Steric
(153)
(154)
(155)
effects are considered to be negligible. Shifts in the phenol OH bands and borane BH bands have also been correlated with the basicities of donor cyclic and acyclic Thiophosphites.212When thiophenol is used, the shifts of v(SH) are phosphorus acids (1 54; Y = Et or OEt) have also been used as hydrogen donors, and v(SH) was correlated with CTIconstants of the phosphorus sub~tituents.~'~ The sulphonylaminophosphonates (1 5 5 ) in carbon tetrachloride have i.r. spectra corresponding to d i m e r ~ , (cf. ~ ' ~ ref. 30e). Alcohol and acetonitrile interactions with diphosphonium salts,216and chlorophyll-tributyl phosphate interaction^,^^^ have also been studied by i.r. spectroscopy.
4 Microwave Spectroscopy There have been few studies reported which utilize this method. Microwave data for dimethylcyanophosphine (1 56) gave bond lengths and angles consistent with those in
207 208
209
210
211 212 213 214
Z15 216 217
M. I. Shandruk, N. I. Yanchuk, and A. P. Grekov, J. Gen. Chem. (U.S.S.R.), 1974,44,2386. R. R. Shagidullin, E. P. Trutneva, N. I. Rizpolozhenskii, and F. S. Mukhametov, Bull. Acad. Sci. U.S.S.R., 1974,23, 1226; R. G. Islamov, I. S. Pominov, M. G . Zimin, A. A. Sobanov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 488. B. N. Laskorin, V. V. Yakshin, and B. N. Sharapov, Proc. Acad. Sci., U.S.S.R., 1974,218,980. E. V. Ryl'tsev, V. G. Koval, V. Ya. Semenii, andYu. P. Egorov, Teor. ieksp. Khim., 1974,10, 347. B. N. Laskorin, V. V. Yakshin, and B. N. Sharapov, Proc. Acad. Sci., U.S.S.R., 1974,218,934. L. J. Van de Griend, D. W. White, and J. G. Verkade, Phosphorus, 1973,3,5; D. W. White and J. G. Verkade, Phosphorus, 1973, 2, 9. 0. E. Raevskaya, R. A. Cherkasov, G . A. Kutyrev, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 717. N. V. Kashina, G. A. Kutyrev, I. P. Lipatova, R. A. Cherkasov, and A. N. Pudovik, J . Gert. Chem. (U.S.S.R.), 1974, 44, 485. L. Almasi, N. Popovici, and A. Hantz, hfonatsh., 1973, 104, 1360. I. E. Boldeskul, G. A. Kalyagin, Yu. P. Makovetskii, and E. V. Ryl'tsev, Optika i Spektroskopiya, 1974, 37, 803. J. P. Leicknam, M. Henry, and E. ROUX,Compt. rend., 1974, 278, I?, 467.
Physical Methods
255
trimethylphosphine and tricyanophosphine.218 The total dipole moment of (156) was 4.1 1 D. A microwave study of methoxydifluorophosphine (157), and three isotopic derivatives, showed that the internal rotational barrier was quite low (422 cal ~ O I - ~This ) .was ~ ~ attributed ~ to minimized stereochemical interactions.A theoretical study indicated that the molecule exists in two gauche conformations.220Rotational assignments have been reported for phosphine,221and the rotational barriers in methylphosphines have been estimated by CNDO 5 Electronic Spectroscopy Absorption.-The extent of n-bonding in a series ofpava-substitutedtriarylphosphines (158) has been estimated from the U.V. The lowest-energy band of triarylphosphines is sensitive to the presence of o-methyl groups [e.g.(159)] and is shifted to longer wavelengths.224 The intensity of this band in the spectra of phenylphosphonium salts (160) is roughly additive with the number of phenyl groups.22sIt is suggested
(158)
(159)
(160)
that the transition can be considered as an inductive perturbation by the R,P group on the remaining phenyl group. The interpretation of the spectra of tetra-arylphosphoiiium salts which bear p-methoxy- and p-dimethylamino-groups is straightforward if the spectra are considered as anisole and dimethylaniline derivatives bearing a - M substituent.226A theoretical study indicated that the substituents on phosphorus may influence the mesomeric properties of a phosphorus atom towards an aromatic system without altering the phosphorus atom’s ability to act as a barrier to c ~ n j u g a t i o n The . ~ ~ U.V. spectra of iodophenylphosphonic and bis(iodopheny1)phosphinic acids indicated only small conjugative interactions involving the iodine atoms.227A comparison of the spectra of the phosphinimines (161) with disubstituted benzenes (162) indicated that in the excited state the C,H,PPh,=N group weakens
(163‘1 218 219 220 221 222 223 224
225 226
237
J. R. Durig, A. W. Cox, and Y. S. Li, Inorg. Chem., 1974, 13, 2302. E. G. Codding, C. E. Jones, and R. H. Schwendeman, Inorg. Chem., 1974, 13, 178. G. Robinet, J. F. Labarre, and C. Leibovici, Chem. Phys. Letters, 1974, 29, 449. F. Y. Chu and T. OkayJ. Chem. Phys., 1974,60,4612; P. K. L. Yin and K. N . Rao, J . Mot. Spectroscopy, 1974, 51, 199. M. S. Gordon and L. Neubauer, J. Amer. Chem. SOC.,1974,96,5690. 0.A. Yakutina, G. V. Ratovskii, Yu. L. Frolov, V. G. Rozinov, and L. M. Sergienko, Voprosy Mol. Spektrosk., 1974, 224.
B. I. Stepanov, A. I. Bokanov, A. B. Kudryavtsev, and Yu. G. Plyashkevich, J. Gen. Chem. (U.S.S.R.), 1974, 44,2312; A. I. Bokanov, N . A. Rozanel’skaya, and B. I. Stepanov, ibid., p. 732. M. Gouterman and P. Sayer, J. Mol. Spectroscopy, 1974, 53, 319. L. Horner and U. M. Duda, Phosphorus, 1975, 5, 109. L. D. Freedman and R. P. Demott, Phosphorus, 1974, 3, 277.
Organophosphorus Chemistry
256
_.
the transmission of electronic effects by a factor of ll-22.228 On the other hand, EHT and PPP calculations on tri-a-pyrryl- and tri-a-furyl-phosphine oxides (1 63) indicate the involvement of d-orbitals, and it is suggested that the long-wavelength band may be considered as a charge-transfer band, with the P=O group conjugated with the heterocyclic ring, at least in the excited Furthermore, in studies of the di-acetylenic compound (164), it was found that the introduction of the dimethylamino-group Y leads to the appearance of an additional band at 350 nm ( E 7.4 x 103).230 This observation has also been attributed to delocalization through phosphorus. The influence of substituent Y on the U.V. spectra of substituted a-cyanostyrylphosphonates (165) can be expressed by a Daub Vandendelt equation (Amax= 1.96Ao+ 232) except for the nitro-s~bstituent.~~~ The low-energy band of the acylphosphine oxides (166) undergoes a bathochromic shift when two bulky Psubstituents are introduced.lg7 A bright orange, benzene-soluble, dithioic acid complex has been assigned the structure (167).232
Photoelectron.-Ab initio calculations on phosphabenzene, arsabenzene, and pyridine reproduced the inversion of the energy sequence of the a,, and b,, orbitals on going from pyridine to phosphaben~ene.~~~? 31e Ionization potentials have also been calculated for p h o ~ p h a b e n z e n e .The ~ ~ ~orbital energies in the photoelectron correlation diagram of phosphaphenanthrene (1 68) are very similar to those for the corresponding ~ h e n a n t h r e n eThe . ~ ~ P(2p) ~ binding energies of the diphosphines (1 69), (1 70),and (171) (130.5, 131.2, and 131.6 eV, respectively) increased with increased electronegativity of the carbon atoms. Quaternization of one of the phosphorus atoms raised the binding energies for both phosphorus atoms, but the binding energy of the 228 229 230 231
s32 233 234 235
I. N. Zhmurova, V. G . Yurchenko, V. P. Kukhar, and L. A. Zolotareva, J. Gen. Chem. (U.S.S.R.), 1974, 44, 70. V. V. Penkovsky and E. D. Lavrinenko-Omecinskaja,Phosphorus, 1974, 3,247. B. I. Stepanov, L. I. Chekunina, and A. I. Bokanov, J. Gen. Chem. (U.S.S.R.), 1973, 43,2627. A. V. Chernova, R. R. Shagidullin, G . A. Kutyrev, G . E. Yastrebova, R. A. Cherkasov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 707. L. I. Samarai, N. V. Mel'nichenko, V. I. Gorbatenko, and 0. Ya. Vasilenko, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2541. D. T. Clark and I. W. Scanlan, J.C.S. Faraday II, 1974, 70, 1222. K. W. Schulte and A. Schweig, Theor. Chirn. Acta, 1974, 33, 19. W. Schaefer, A. Schweig, F. Bickelhaupt, and H. Vermeer, Rec. Tratj. chiin., 1974, 93, 17.
Physical Methods
257
PIII atom then became constant and independent of the type of bridge.236 Replacement of PhzPby Me,N also increased the binding energy of the PII1atom but the Me3Nf group had a smaller effect than the quaternary phosphonium group. The photoelectron spectra of cyclic polyphosphines indicate that d,-bonding is relatively The P ( B p )binding energy of the stabilized ylide (172; Y = Alk) is lower than that of (172; Y = OMe).238Triphenylphosphine oxide and sulphide
Me,NP P%P=CHCOY
(172)
/y
\
C&
(173)
P ~ P K m R ) 13 , (174)
have intermediate values. All are lower than the binding energies of phosphonium salts. The trend of the phosphorus and nitrogen lone-pair ionization potentials of the aminophosphines (173) suggests that the PN torsional barriers arise predominantly from steric and lone-pair repulsion effects and that d,-p, bonding is of little import a n ~ eE.S.C.A. . ~ ~ ~ spectra, which have been reviewed for phosphorus confirmed the structure of the unusual ester (174).241 Fluorescence.-Aminophosphoric esters exhibit a weak fluorescence which has been attributed to their non-planar A spectral study of a flavine-labelled n ~ c l e o t i d eand ~ ~ the ~ X-ray fluorescence spectra of phosphate anions244have been reported.
6 Rotation and Refraction Magneto-optical studies of l-methyl- and l-butyl-phosphole (175) have been reported.245The magnetic molecular rotations are even lower than those calculated for a W. E. Swartz, R. C. Gray, and J. C. Carver, Spectrochim. Acta, 1974, 30A, 1561. A. H. Cowley, M. J. S. Dewar, D. W. Goodman, and M. C. Padolina, J. Amer. Chem. SOC., 1974,96, 3666. 238 M. Seno, S. Tsuchiya, and T. Asahara, Chem. Letters, 1974, 405. 239 A. H. Cowley, M. J. S. Dewar, J. W. Gilje, D. W. Goodman, and J. R. Schweiger, J.C.S. Chem. Comm., 1974, 340. Z4O A. Fukuhara, K. Usami, A. Yanagisawa, M. Kuroda, Y. Goto, A. Shibata, H. Matsushita, and Y. Takehana, Proc. Internat. Conf. X-ray Opt. Microanal. 6th, 1971 (publ. 1972), p. 385. 241 D. Weber and E. Fluck, Z. Naturforsch., 1975, 30b, 60. 2 4 2 V. G. Gamalei, V. F. Gachkovskii, V. D. Pak, and N. S . Kozlov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 729. 243 V. V. Mishchenko, T. A. Shapiro, Yu. M. Rubchinskaya, D. S. Khristianovich, E. D. Khomutova, and V. M. Berezovskii, J. Gen. Chem. (U.S.S.R.), 1973,43, 2531. 2 4 4 . G. N. Dolenko, A. P. Sadovskii, L. N. Mazalov, and A. A. Krasnoperova, Izuest. Akad. Nuuk, S.S.S.R., Ser-fiz., 1974, 38, 603. 245 M.-F. Bruniquel, J.-F. Labarre, and F. Mathey, Phosphorus, 1974, 3, 269. 236
237
10
Organophosphorus Chemistry
258
localized model, which indicates that there is little cyclic delocalization of the nelectrons. A theoretical study of the aromaticity of these molecules indicated that d,-p, conjugation may play a key role even in the planar On the other hand, pn-pn conjugation increased with increased planarity of the molecule. Circular dichroism studies of the conformational stabilityof dinucleosidephosphates have been reported.247The refraction of the P-F bond has been estimated to be 4 k 0.7.248
7 Diffraction X-Ray.-The crystal structure of the phosphanaphthalene (176) 249 has been determined. The molecule has nearly planar rings and bond-length variations similar to
those of naphthalene. Details of the structure of a phosphadiazole have been publi~hed.~~f~ 250 The phosphines (177) 251 and (1 78) 252 have pyramidal configurations. The former molecule has two methyl groups orientated towards the phosphorus lone pair of electrons, which is the reverse of the conformation of the chalc~genides.~~f Transesterification of trimethyl phosphite by meso-hydrobenzoin gave (179).253The P-0 bond lengths are larger and OPO angles smaller in the cyclic Ph
(179) 246 247 248 249 250
251 252 253
G. Kaufmann and F. Mathey, Phosphorus, 1974, 4, 231. N. P. Johnson and T. Schleich, Biochemistry, 1974, 13, 981. L. A. Maijs, Chem. Abs., 1973, 7 8 , 151 757. J. J. Daly and F. Sanz, J.C.S. Dalton, 1974, 2388. V. G. Andrianov, A. E. Kalinin, and Yu. T. Struchkov, Zhur. strukf. Khim., 1974, 15, 1127. T. S. Cameron and K. Miller, Cryst. Strucf. Comm., 1974, 3, 489. C. Krueger and P. J. Roberts, Cryst. Struct. Comm., 1974, 3, 707. M. G. Newton and B. S. Campbell, J . Amer. Chem. SOC., 1974, 96, 7790.
Physical Methods
259
phosphite (179) than in the corresponding phosphate. The crystal structure of the cyclic diaminophosphine (1 80) has an almost planar heterocyclic ring with trigonal nitrogen and the methylene protons appear as a sharp doublet in the n.m.r. spectrum. On the other hand, one of the heterocyclic rings of the spirophosphonium salt (7) is bent such that the benzene rings make an angle, relative to one another, of 14.5O;l9 the other ring is planar. The PC and PN distances are consistent with aromatic heterocyclic rings (cf.SP,p. 229). A non-planar heterocyclic ring was deduced from the n.m.r. spectra of the oxygen heterocycles (181).31C However, the X-ray diffraction data on the tetraphenyl derivative (181; R = Ph) show the ring to be
0
I1
Ph,PCHCMe=CI-&
1 Me
Ph,P=C
/"" NC'
Ph, P
\\
Me0,C
/c-c\
yCHPh CO, Me
(184)
nearly planar in the crystal and to have bond lengths in accordance with a certain The cyclodiphosphadecane (1 82) has the normal cyclodegree of delocalizati~n.~~~ decane conformation, with extra-annular pseudo-axial phenyl ~ u b s t i t u e n t ~ . ~ ~ ~ Crystal structures of the oxides (1 83) ll9 and (1 84) 257 have been determined, and also of a number of phosphonium ylides (185),258(186),259(187),260and (188).261The central proton of the ylide (187) appears to exert a similar stereochemical influence as the unshared electron pair of the diphosphorane.260The PCC angle of the 'cumulene' chain of (188) is 125.6", which indicates an appreciable contribution of the ylidic 254
255 2S6 257
J. C. Clardy, R. L. Kolpa, J. G. Verkade, and J. J. Zuckerman, Phosphorus, 1974, 4, 145. J. Guilhem, Cryst. Struct. Comm., 1974, 3,227. M. Draeger, Chem. Ber., 1974, 107,3246. F. Allen, 0. Kennard, L. Nassimbeni, R. Shepherd, and S. Warren, J.C.S. Perkin 11, 1974, 1530.
258
259 260
W. Dreissig, H. J. Hecht, and K. Plieth, Z . Krist., 1973, 137, 132. U. Lingner and H. Burzlaff, Acta Cryst., 1974, B30, 1715. P. J. Carroll and D. D. Titus, Cryst. Struct. Comm., 1974, 3, 433.
Organophosphorus Chemistry
260
(192)
form to its structure.261The conformation of the heterocyclic ring of the cyclic phosphonate (189) was neither chair nor boat.262Unlike the P=O group in 2-0x01,3-dioxaphosphorinans,which is frequently equatorial, the P=S group in (190) is The P=O group is also axial in the diamide (191), with the ring flattened at the phosphorus end of the ring, as in the 1,3,2-dio~aphosphorinans.~~~ The crystal structure of the bicyclic thiophosphate (192) showed that the presence of the PII1 atom in place of carbon allows the POC bond angles to open from 115" to 119°.2ss The two phosphorus atoms are able to acquire bond angles and lengths which are quite typical of acyclic phosphates and phosphines. The structures of the phosphonates (193),266 (194),267 and (195)268have also been established by X-ray diffrac-
(193)
(196) 261 262 263 264 265
266 267 268
H. Burzlaff, U. Voll, and H. J. Bestmann, Chem. Ber., 1974, 107, 1919. S. R. Holbrook, D. van der Helm, and K. D. Berlin, Phosphorus, 1974, 3, 199. J. P. Dutasta, A. Grand, and J. B. Robert, Tetrahedron Letters, 1974, 2655. J. C. Clardy, J. A. Mosbo, and J. G . Verkade, Phosphorus, 1974, 4, 151. J. C. Clardy, D. C. DOW,and J. G . Verkade, Phosphorus, 1975, 5, 8 5 . J. Iball, P. Kaye, and J. A. Millar, J.C.S. Perkin It, 1974, 650. A. J. Collins, G . W. Frazer, P. G . Perkins, and D. R. Russell, J.C.S. Dalton, 1974, 960. G . H. Y. Lin, D. A. Wustner, T. R. Fukuto, and R. M. Wing, J. Agric. Food Chem., 1974,22, 1 134.
Physical Methods
261
tion. The oxidation of cyclophosphamide has been shown to give the cytotoxic peroxide (196).269Crystal structures of a number of nucleotides and other biologically involved phosphates have been determined.270 The data 271 and methods 272 have been reviewed. The PN bond length involving the onium phosphorus atom in (197)
I
x-
is shorter (165 pm) than that involving the PI1*atom (171 pm).273An even shorter PN bond (159 pm) has been reported for the triamide (198), which has nearly perfect C,, The cyclic polyphosphine (199) has phenyl rings nearly perpendicular to the slightly puckered five-membered ring.275Crystal structures of a polyp h o s p h a ~ e n eand ~ ~the ~ diphosphadiazine (200) 277 have been determined. Although the ring of (200) is puckered, all the bond lengths correspond to partial double-bond character. The interest in the stereochemistry of five-co-ordinatephosphoranes has led to the The phosphorus ligands of determination of a number of their crystal the spiro-oxyphosphorane(26) have stereochemistry intermediate between t.b.p. and square-pyramidal,whereas the methyl derivative (201) is closer to a square-pyramidal arrangement.278On the other hand, the spirophosphorane (202; X = CF,) is essentially t.b.p.;279the PC bond is unusually long (180.5 pm) and the radial orientation of the sulphur atom probably reflects its lower apicophilicity compared to oxygen. The amino-derivatives (203)280and (204) 281 are also essentially t.b.p. 269 270
27l
272 273 274 275 276
277 278
279 280
381
H. Sternglanz and H. M. Einspahr, J. Amer. Chem. SOC.,1974, 96,4014. P. B. Hitchcock, R. Mason, K. M. Thomas, and G. G. Shipley, Proc. Nat. Acad. Sci. U.S.A., 1974, 71, 3036; D. W. Young, P. Tollin, and H. R. Wilson, Acta Cryst., 1974, B30, 2012; G. R. Freeman and C. E. Bugg, ibid., 1975, B31,96; 0. Kennard, N. W. Isaacs, and W. D. S. Motherwell, Chem. Abs., 1974,81,46 536; T. P. Seshadri and M. A. Viswamitra, Current Sci., 1974, 43, 1 1 1 ; M. A. Viswamitra and T. P. Seshadri, Nature, 1974, 252, 176; P. De Meester, D. M. L. Goodgame and T. J. Jones, Biochim. Biophys. Acta, 1974, 353, 392; B. Hingerty, E. Subramanian, S. D. Stellman, S. B. Bryde, T. Sato, and R. Langridge, Biopolymers, 1975, 14, 227; V. Sasisekharan, S. Zimmerman, and D. R. Davies, J. Mol. B i d , 1975, 92, 171. A. R. Hagen, Acta Odontol. Scand., 1973, 31, 149; J. R. Van Wazer, in ‘Environmental Phosphorus Handbook‘, Wiley, London, 1973, p. 169. E. F. Kaelbe, in ‘Environmental Phosphorus Handbook‘, Interscience, Chichester, 1973, p. 341. G. W. Hunt and A. W. Cordes, Znorg. Chem., 1974, 13, 1688. J. C. Clardy, R. L. Kolpa, and J. G. Verkade, Phosphorus, 1974, 4, 133. H. P. Calhoun and J. Trotter, J.C.S. Dalton, 1974, 386. S. H. Bishop and 1. H. Hall, Chem. A h . , 1975, 82, 31 614. J. Weiss, Acta Cryst., 1974, B30, 2888. H. Wunderlich and D. Mootz, Acta Cryst., 1974, B30, 935; H. Wunderlich, D. Mootz, R. Schmutzler, and M. Wieber, Z. Naturforsch., 1974,29b, 32; €I. Wunderlich, Acta Cryst., 1974, B30, 939. E. Duff, D. R. Russell, and S. Trippett, Phosphorus, 1974, 4, 203. M. G. Newton, J. E. Collier, and R. Wolf, J. Amer. Chem. SOL, 1974, 96, 6888. A. E. Kalinin, V. G. Andrianov, and Yu. T. Struchkov, Zhur. strukt. Khim., 1974, 15, 1132.
262
Organophosphorus Chemistry
structures with trigonal nitrogen atoms. An X-ray diffraction study of the fluorophosphorane (205) confirmed the conclusion from its n.m.r. data that it possesses a hexaco-ordinated phosphorus atom.41 Electron.-The structure of phosphabenzene has been studied by electron diffraction. Combination of the data with microwave rotational constants enabled the identification of two different CC bond lengths (138.4 and 141.3 pm).282&Orbitals are involved mainly in the two highest occupied molecular orbitals, i.e. the lone-pair orbital and the out-of-plane n-bonding orbital. The study supports previous evidence that phosphabenzene has aromatic character. An electron-diffractionstudy of trimethyl phosphite has done little to resolve the problem of its preferred c o n f o r m a t i ~ nThe .~~~
vapour-phase conformation of the aminophosphine (206) has the trigonal dimethylamino-groups rotated - 14.1 k 5.6" and 65.6 k 3.4"from the plane orthogonal to the NPN Data on the dithiophospholan (207) fit best a phosphorus edgeenvelope conformation with an axial chlorine atom.285The PN bond length (168 pm) of gaseous bis(difluorophosphino)amine (208) corresponds to 30 % double-bond 282
283 284
285
T. C. Wong and L. S. Bartell, J. Chem. Phys., 1974, 61, 2840. N. M. Zaripov, V. A. Naumov, and L. L. Tuzova, Proc. Acad. Sci., U.S.S.R.,1974,218, 972. N. M. Zaripov, V. A. Naumov, and L. L. Tuzova, Phosphoriis, 1974, 4, 179. G. Y. Schultz, I. Hargittai, J. Martin, and J. B. Robert, Tetrahedron, 1974, 30, 2365.
Physical Methods
263
character.286It has been found that the PF bond length of (209) corresponds to that in POF3 whilst the PO bond length is similar to that in trimethyl 8 Dipole Moments, Permittivity, and Folarography The dipole moment of a non-bonding pair of electrons of PII1compounds was estimated to be 0.91 D for the thiophosphite (210).288Its dependence on the geometry of the molecule was discussed. The dipole moments of a wide range of
phosphorus bonds were calculated, taking into account the moment of the free pair of Limitations of an additivity scheme for compounds of different valence-type have also been discussed. CNDO calculations of the dipole moments of methylphosphine (21 1) predict a charge transfer from phosphorus to carbon.290The dipole moments of dialkyl-p-tolylphosphines (212) indicate that the lone pair of electrons is in the same plane as the aryl ring, and therefore the possibility of pn-pn conjugation is excluded.291The dipole moments of the acetylenic PII1 compounds (213; Y = Ph, OEt, or NEt2;Z = H, Alk, or Ph) indicate that d,-p, conjugation occurs and that it decreases in the order amides < phosphines < p h o s p h ~ n i t e s . ~ ~ ~ However, pn-pn conjugation may be important for the acetylenic phosphine (213 ;
Y = Ph, Z = CF3). The moments of thirty cyclic and acyclic phosphites and . ~ ~ ~ momentaminophosphites(214)have been related to their c o n f o r m a t i o n ~Dipole Kerr data on the one hand, and electron diffraction-n.m.r. data on the other, have come to different conclusions regarding the conformational preferences of cyclic chl~rophosphites.~~~ The discrepancies may be due to the choice of inaccurate electro-optical parameters. Calculations, based on parameters obtained from a combination of the depolarization of the Rayleigh light scattering with the dipole moments and Kerr constants, favoured the chair conformation with an axial P-Cl bond, in agreement with the n.m.r. and diffraction The P--0 and P-Cl 286 287
288
289 290
291 292
293 294
E. Hedberg, L. Hedberg, and K. Hedberg, J. Amer. Chem. SOC.,1974, 96, 4417. W. Zeil, H. Kratz, J. Haase, and H. Oberhammer, Z . Nuturforsch., 1973, 28a, 1717. E. I. Matrosov, G. M. Petov, and M. I. Kabachnik, Zhur. strukt. Khim, 1974, 15, 250. E. I. Matrosov, G. M. Petov, and M. I. Kabachnik, Zhur. strulct. Khim, 1974, 15, 255. M. S. Gordon and L. Neubauer, J . Amer. Chem. SOC.,1974,96, 5690. 0. A. Raevzkii, A. N. Vereshchagin, Yu. A. Donskaya, F. G. Khalitov, I. G. Malakhova, and E. N. Tsvetkov, Bull. Acud. Sci. U.S.S.R.,1974, 23,422. K. S. Mingaleva, L. A. Tamm, V. N. Chistokletov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1974, 44, 101. D. Besserre and M. Troquet, Bull. SOC.chim. France, 1974, 845. B. A. Arbuzov, S. G. Vul’fson, and R. P. Arshinova, Phospliorus, 1974, 4, 221.
264
Organophosphorus Chemistry
bond moments of chloro-phosphites were estimated to be 0.90 and 1.85 D, respecof dioxaphosphorinans (215 ; R = Et or Ph) has an axial t i ~ e l yThe . ~ alkoxy-group ~~
OR
Me
orientation, according to a graphical analysis of their dipole moments and Kerr constants.2gsAlthough X-ray diffraction showed the sulphide group of (190) to be axial, the dipole moment (5.78 D) of the closely related sulphide (216) corresponds to the alternative conformer with an axial methyl.297Studies of the dithiaphospholan sulphides (217; Y = Me, Et, or C1) indicated that the P-S bond moment varies with the nature of the P-substituent. A P-S bond moment of 0.26 D was obtained for the methyl derivative (this is revised from the previous e~tirnate)~lf and a ~ ~ n moments d . ~ ~ *of ethylenic and moment of 0.56 D for the ~ h l o r ~ - ~ ~ m pDipole &keto-phosphonate~,~~~ hydrogen phosphonates, monoalkyl phosphates, and dialkyl phosphates 300 have also been measured. Theoretical studies of the effective atomic charges on phosphoryl groups and their effects on dipole moments have been Dipole moments have been used for the conformational analysis of acylmethylenephosphoranes (218) and an ester-stabilized iminophosphorane
(219).302A tentative value of the P=N bond moment has been calculated. The ylide contribution to the structure of a series of cyclopentadienylides (220) has been estimated to decrease in the order for M of Sb > As > P S Se > S 3 0 3 Solvent effects on the dipole moments of triphenylphosphine, its oxide, and sulphide have been determined.304Hydrogen-bonding of trialkylphosphine oxides to chloroacetic acid, 295 296 297 298
299
300 301
302 3O3
304
D. Besserre and M. Troquet, Bull. SOC.chim. France, 1974, 852. B. A. Arbuzov, R. P. Arshinova, S . G. Vul’fson, and E. T. Mukmenev, Bull. Acad. Sci. U.S.S.R., 1973, 22, 2372. D. A. Predvoditelev, D. N. Afanas’eva, and E. E. Nifant’ev, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1667. E. A. Ishmaeva, R. A. Cherkasov, V. V. Ovchinnikov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2633. G. Peiffer and P. Courbis, Canad. J. Chem., 1974, 52, 2894, I. Chromy and A. Budniok, Chem. Abs., 1975, 82, 50 359. 0. P. Charkin, Zhur. strukt. Khim., 1974, 15, 320; 0. A. Raevskii, V. E. Bel’skii, and V. V. Zverev, Bull. Acad. Sci. U.S.S.R., 1973,22, 2432; 0. A. Raevskii and Yu. A. Donskaya, Bull. Acad. Sci. U.S.S.R., 1973, 22, 2435. H. Lumbroso, D. M. Berth, and P. Froyen, Bull. SOC. chim. France, 1974, 819. H. Lumbroso, D. Lloyd, and G . S. Harris, Compt. rend., 1974, 278, C,219. J. R. Masaguer Fernandez, C. Lorenzo, J. S. Casas, M. V. Coto, J. Sordo, and M. R. Bermejo, Chem. A h . , 1974, 81, 62 928.
Physical Methods
265
propanol, and phenol has been studied by permittivity measurements (the dielectric constant was plotted against composition of complexing compound, being in carbon tetrachloride or chlorobenzene The stereochemistries of the complexes were compared with the hydrogen-bond strengths. Permittivity measurements indicated that dialkyl phosphonates are not hydrogen-b~nded.~~~ The dielectric permeability and relaxation properties of a wide range of phosphoryl compounds have been correlated with The aromaticity of the heterocyclic ring of dibenzophospholium salts has been investigated by polarographic reduction,308and the electrochemical reduction potentials of cyclopolyphosphines were found to be independent of the ring size.3o9
9 Mass Spectrometry The mass spectra of a number of triarylphosphines310 and biphenylylphosphines311 have been interpreted. Field ionization spectroscopy showed that the P-aryl bond strengths of phosphines and salts increase in the order Ph
isomeric phosphabenzene apart from the molecular The mass spectra of the several phosphole derivatives, (222),314(223),315and (224),316have been interpreted. The main fragmentation of the dibenzophospholes (224) and their chalcogenides involves loss of the alkyl group.316The fragmentation patterns of the endo- and exoisomers were similar for the unsaturated phosphonates (225) but different for the saturated phosphonates (226).317The fragmentations were found to be dominated by 305 306 307
308 309 310 311 312 313 314
315 316 317
Yu. Ya. Borovikov, Yu. P. Egorov, V. P. Chobanya, and V. Ya. Semenii, J. Gen. Chem. (U.S.S.R.), 1974, 44,987. Ya. A. Levin, E. I. Vorkunova, B. E. Ivanov, F. G. Khalitov, and 0. A. Raevskii, J. Gen. Chem. (U.S.S.R.), 1974,44, 1671. M. F. Shears, G . Williams, A. J. Barlow, and J. Lamb, J.C.S. Faruduy 11, 1974, 70, 1783; V. I. Katolichenko, Yu. P. Egorov, Yu. Ya. Borovikov, and V. Ya. Semenii, Teor. i eksp. Khim., 1974, 10, 88. D. W. Allen, J. R. Charlton, B. G . Hutley, and L. C. Middleton, Phosphorus, 1974, 5, 9. T. J. DuPont, L. R. Smith, and J. L. Mills, J.C.S. Chem. Comm., 1974, 1001. J. Gomez Lara, E. Cortes, A. Cabrera, and C. Alvarez, Chem. A h . , 1974, 81, 168 736. D. Hellwinkel, C.Wunsche, and M. Bach, Phosphorus, 1973, 2, 167. L. Horner and U. M. Duda, Phosphorus, 1975, 5, 135. G . Maerkl, H. Hauptmann, and F. Lieb, Phospltorus, 1974, 4, 279. F. Mathey, Tetrahedron, 1974, 30, 3127. T. H. Chan and K. T. Nwe, Phosphorus, 1974, 3, 225. V. N. Bochkarev, A. N. Polivanov, V. I. Aksenov, E. P. Bugarenko, and E. A. Chernyshev, J. Gen. C k m . (U.S.S.R.), 1974, 44, 1251. H.J. Callot and C. Benezra, Org. Mass Spectrometry, 1971, 5, 343.
266
Organophosphorus Chemistry
the localization of the charge on the phosphorus moiety. The base peaks occurred at m/e 137, which corresponds to the hydroxyvinylphosphonium ion (227). Electron impact of the a-dichloroalkyl compounds (228) has been reported to give carbonyl fragments. Their formation was rationalized by a Cl, 0 exchange reaction as shown in Scheme l.318Mass spectra have been reported on polymeric anhydrides,319 0
II RCC4PCL, -+
0
II
RY-PCh
RklPCI,
0
RCO'
II+
-f-
RCPCS
Scheme 1
fluorophosphazeiies,320and a cyclic phosphenyl Metastable ions indicated that the parent cations of arylphosphonic difluorides have the three-co-ordinate The thermal decomposition of 2-aminoethylphosphonic acid in the structure (229).322 mass and the identification of aminoalkylphosphonic acids from the spectra of their trimethytsilyl derivatives,3z4have been reported. The most abundant
(229)
(230)
ions in the positive-ion spectra of the diphosphetidine (230) corresponded to ( M / 2 )+ 1, M / 2 , and ( M / 2 )- 1 but the negative-ion spectrum of (238;Y = C6H4CF3) had a molecular ion as the most abundant Ion cyclotron resonance spectro3l8 319 320 321 322 323 324 385
G. Schmidtberg, G. Haegele, and G. Bauer, Org. Mass Spectrometry, 1974, 9 , 844. K. Moedritzer, Phosphorus, 1974, 3, 219. P. L. Toch, J.C.S. Daltoii, 1973, 1685. E. R. Kennedy and R. S. Macomber, J . Org. Chem., 1974, 39, 1952. L. W. Daasch and R. W. Gamache, Chem. Abs., 1974, 81, 119 373. A. G. Menke and F. Walmsley, Phosphorus, 1974, 4, 287. D. J. Harvey and M. G. Homing, Org. Mass Spectrometry, 1974, 9, 1 1 1, 955. 0. Schlak, R. Schmutzler, and I. K. Gregor, Org. Mass Spectrometry, 1974, 9, 582.
Physical Methods
267
scopy has been used to study the basicities and ion-molecule reactions of methylpho~phines.~,~
10 PKa and Therinocliemical Studies Kinetic acidities obtained from proton exchange rates give only an approximate guide to carbanion stabilities, and the order in a series may be different from that obtained from pKa measurements.327 Thus the rates of proton exchange decrease in the order PhSMeSPhPMe, > PhMe whereas pKa decreases in the order PhPMe, > PhSMe > PhMe. The acid strengths of phosphonic and phosphinic acids (231 ; 0 PhP, II/OH YPO,H,
Y,PO,H
(231)
(232)
, OCKCHEtBu
(233)
Y = Alk) and (232; Y = Alk) increase in the order for R of Ph
x-
II
YzPCH,CO, H
Y,PO
proton of (234) is the last to dissociate. Calculations of G* and c; constants from the PKa’S of a series of phosphorus-substitutedacetic acids (235 ;Y = R,OR, Ar, OAr, or NR,) showed that the P=O group is one of the best conductors of electronic Potentiometric titration of phosphine oxides and amides (236; Y = R or NHR) against perchloric acid in nitromethane indicated that protonation is accompanied by association of the conjugate acid and base. This appeared as a second 326 327 328
329 330 331 332
333
R. H. Staley and J. L. Beauchamp, J. Amer. Chem. Soc., 1974, 96, 6252. F. G. Bordwell, W. S. Matthews, and N. R. Vanier, J . Amer. Chem. SOC.,1975, 97, 442. L. P. Zhuravleva, S. N. Solodushenkov, and A. A. Petraslienko, Chem. A h . , 1974, 80, 132 640. N. N. Guseva, E. V. Sklenskaya, M. Kh. Marapet’yants, and A. I. Mikhailichenko, Chem. A h . , 1974, 81, 12 981. L. L. Spivak, A. A. Grigor’eva, T. A. Mastryukova, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 8 3 8 . N. A. Adaikin, E. S. Barketov, and A. A. Zaitsev, Rndiokhimiya, 1974, 16, 186. A. Yu. Kireeva, B. V. Zhadanov, V. V. Sidorenko, and N. M. Dyatlova, J. Gen. Chem. (U.S.S.R.), 1973,43,2494; L. V. Nikitina, A. I. Grigor’ev, and N. M. Dyatlova, ibid., 1974,44, 1568. E. N. Tsvetkov, R. A. Malevannaya, L. I. Petrovskaya, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 1203.
268
Organophosphorus Chemistry
inflection in the titration curve.334Substituent constants and p&’s have been determined for the phosphonothioureas (237),335the phosphinimines (238) 228 and (239),3’6 0
II
RNHCSNHPY,
Ar,P=NAr
Ph,P=NPP&=NAr
and cycloph~sphazenes.~~~ Differential thermal analysis has been used in the study of the phosphonate -phosphate r e a ~ r a n g e m e n tthe , ~ ~reaction ~ of phosphorus chlorides and the thermal characterization of tetramethylphosphonium with Differential scanning calorimetry has been found to be a convenient method of determining optical The small amount of racemate contained in an enriched optically active enantiomer may be regarded as an impurity. This impurity produces a second small peak in the d.s.c, thermogram, and as little as 1 % of racemate can be detected. 11 Chromatography and Surface Properties The chromatographic behaviour of phosphorus oxyacids has been reviewed.342 G.1.c. separation of dialkyl phosphites has been found to be dependent on G.1.c. has been used to analyse cyclic tetra- and p e n t a - p h ~ s p h i n e sand ~ ~ ~a wide range of biologically important organophosphorus Pho~phonate~~~ and phosphate347esters have also found a use as stationary phases for the separation of hydrocarbons and phenols. T.1.c. behaviour of dialkyl phosphates (240) using aqueous-organic e l u a n t ~ , the ~ ~ *separation of phenols and aryl phosphates,349and 334 335
E. P. Buchikhin, V. V. Yakshin, and V. I. Medvedev, J. Gen. Chem. (U.S.S.R.), 1974,44,1330. V. A. Alekseenko, M. M. Kremelev, and V. I. Dulova, Chem. Abs., 1974, 81, 37 365. I. N. Zhmurova, A. P. Martynyuk, A. S. Shtepanek, V. A. Zasorina, and V. P. Kukhar, J , Gen. Chem. (U.S.S.R.), 1974, 44,76. 337 S. N. Nabi and R. A. Shaw, J.C.S. Dalton, 1974, 1618. 338 G . V. Romanov, R. G. Fitseva, I. V. Konovalova, A. N. Pudovik, and N. P. Burmistrova, J. Therm. Analysis, 1974, 6, 119. 339 S. Kh. Nurtdinov, N. M. Ismagilova, I. G. Filippova, D. V. Shikhmuratova, V. A. Korobchenko, R. B. Sultanova, T. U. Zykova, and V. S. Tsivunin, J. Gen. Chem. (U.S.S.R.),1974,44, 1650. 340 P. R. Nambiar and S. R. Jain, Thermochim. Acta, 1974, 9, 295. 341 R. Luchenback and L. Horner, Thermochim. Acta, 1975, 11, 216. 343 S. Ohashi, in ‘Environmental Phosphorus Handbook‘, Interscience, Chichester, 1973, p. 303. 343 L. S. Subbotina and V. P. Evdakov, Zhur. analit. Khim., 1974, 29, 2238. 344 A. N. Laurent’ev. I. G. Maslennikov, V. A. Efanov, and E. G. Sochilin, J. Gen. Chem. (U.S.S.R.),1974, 44, 2550. 845 V. Pacakova and J. Nekvasil, J. Chromatog., 1974,91,459; T. Curstedt and J. Sjovall, Bioclzim. Biophys. Acta, 1974, 360, 24; S. M. Lee and S. K. Chang, Chem. Abs., 1975, 82, 81 635; B. W. Agranoff and E. B. Seguin, Prep. Biochem., 1974,4, 359; A. L. Majumder and F. Eisenberg, Biochem. Biophys. Res. Comnt., 1974, 60, 133; C. Pantarotto, A. Bossi, G. Belvedere, A. Martini, M. G. Donelli, and A. Frigerio, J. Pharm. Sci., 1974, 63, 1554; H. K. Lee, Chem. Abs., 1975, 82, 68 866. 346 G. V. Tukov, S. Kh. Nurtdinov, L. N. Kalinchuk, V. F. Novikov, and V. A. Zakharov, Chem. Abs., 1975, 82, 45 870. 347 J. Macak, P. Buryan, and J. Hrivnak, J. Chromatog., 1974, 89, 309. 348 A. Lamotte and A. Francina, J. Chromatog., 1974, 88, 109. 349 I. M. Makarenko, Izvest. V. U.Z . Khim. i khim. Tekhnol., 1974, 17, 1 1 16.
336
Physical Methods
269
the determination of a large variety of biologically important compounds 350 have been reported. Aminophosphonic acids have been separated on layers of anion- and cation-exchangers 351 and also by paper chromatography as their nitro-aryl derivat i v e ~Organic . ~ ~ ~ phosphates have been determined by paper chromatography, using a thiocyanate developing reagent. The reagent reacts with uncomplexed FeIII in the paper and leaves the phosphates as white spots on a pink Nucleotides have been analysed by column c h r ~ m a t o g r a p h ybiospecific ,~~~ affinity chromat o g r a p h ~ ,and ~~~ ion-exchange c h r ~ m a t o g r a p h y Phospholipids .~~~ have also been studied by column c h r ~ m a t o g r a p h y . ~ ~ ~
350
35l 352 353
354
355 356
357
E. S. Kosmatyi and B. M.Tverskaya, Chem. Abs., 1974,81, 100 509; E. Grzeskowiak and A. Lewandowski, ibid., 1975, 82, 137 849; G. Voelker, U. Draeger, G. Peter, and H. J. Hohorst, Arzneim.-Forsch., 1974,24, 1172; T. A. Dzhaliashvili and V. N. Chikvaidze, Chem. Abs., 1974, 81, 35 125; M. S. P. Manandhar, and K. Van Dyke, Analyt. Biochem., 1974,58,368 ;K. Potthast, J. Chromatog., 1974,88,168 ; H. Nielsen, J. Chromatog., 1974,89,275 ; B. Banerjee, S. K. Jain, and D. Subrahmanyam, J. Chromatog., 1974,94,342; D. 0 .E. Gebhardt and R. E. De Rooij, Clinica Chim. Acta, 1975,59, 267; P. J. Evans and F. W. Hemming, J. Chromatog., 1974, 97, 293. L. Lepri, P. G. Desideri, and V. Coas, J. Chromatog., 1974, 95, 113. J. Le Pogam, H. Jensen, and E. Neuzil, J. Chromatog., 1973, 87, 179. J. L. Firmin and D. 0. Gray, J. Chromatog., 1974, 94, 294. H. D. Hunger and H. Reinbothe, J. Chromatog., 1974,97,273 ; S . A. Narang, K. Itakura, C. P. Bahl, and N. Katagiri, J. Amer. Chem. SOC.,1974, 96, 7074. P. Brodelius, P. 0. Larsson, and K. Mosbach, European J. Biochem., 1974, 47, 81 ; H. Schott, J. Chromatog., 1974, 96, 79; R. Lamed and A. Oplatka, Biochemistry, 1974, 13, 3137. A. J. Thomas, and K. C. Blanshard, Biochem. SOC.Trans., 1974, 2, 66. H. Nielsen, J. Chromatog., 1974, 89, 259.
Author Index Abd-Elmageed, M. E., 250 Abd el Rahman, M. O., 63 Abdo, W. M., 81 Abernethy, D., 228 Abicht, H.-P., 8 Abraham, K. M., 1, 55, 235 Abramov, I. A., 78 Abromova, K. A., 201 Abul’khanov, A. G., 128 Adaikin, N. A., 267 Adamcik, R. A., 101 Adlkofer, J., 167 Afanas’ Eva, D. N., 264 Agawa, T., 184 Ager, I. R., 46, 222 Agranoff, B. W., 268 Aguiar, A. M., 230 Ahmed, F. R., 210 Ahmed, M., 182 Aime, S., 239 Akasaka, K., 165 Akhmedov, Sh. T., 109 Aksenov, V. I., 265 Aksnes, G., 21, 128 Albagnac, G., 204 Albrand, J. P., 8, 102, 241 Albright, T. A., 24, 200, 234 Aleksandrova, I. A., 53 Alekseenko, V. A., 268 Aliev, R. Z., 53 Alkhoff, W., 234 Allan. D.. 137 Allcock, H. R., 208, 210 Allen, C. W., 205, 208 Allen, D. W., 20, 25, 265 Allen, F. H., 72, 259 Allende. C. C.. 156 Allende; J. E.,’156 Alley, W. D., 95 Almasi, L., 250, 254 Almog, J., 193 Altenau, A. G., 209 Althoff, W., 241 Alton, E. R., 56 Alvarez, C., 265 Aly, H. A. S., 20 Amarskii, E. G., 71 Amit, B., 147, 212 Anathakrishnan, T. R., 60 Anderson, B. M., 131 Anderson, S. E., 23 Anderson, S. P., 8 Andersson, J., 141 Andose, J. D., 25 Andrade, J. D., 132 Andrew, E. R., 229 Andrewes, A. G., 182 Andrianov, K. A., 209 Andrianov, V. G., 29, 31, 64, 258, 261 Andruzzi, F., 65 Aneja, R., 13
Angerer, J., 180 Angus, W. W., 137 Anoshina, N. P., 91,99, 110, 126 Anpilova, L. I., 78 Antkowiak, T. A., 209 Antokhina, L. A., 253 Appel, R., 10, 11, 12, 30, 61, 65, 189, 192, 197, 198, 199, 200, 210 Arai, K., 156 Arbusov, A. E., 70 Arbuzov, B. A., 29, 39, 81, 83, 99, 110, 127, 232, 245, 263, 264 Ardrey, R. E., 235 Arentzen, R., 158 Arimatsu, S., 125 Armstrong, D. R.,204 Armstrong, V. W., 19, 157 Arndt-Jovin, D. J., 153 Arshinova, R. P., 245, 263, 264 Aruldhas, G., 60 Asahara, T., 257 Asai, H., 145 Ashe, A. J., 26, 247 Ashrafullina, L. Kh., 250 Assmann, G., 228 Atavin, A. S., 241 Atkinson, A., 152 Aurbach, G. D., 156 Aviv, H., 164 Awerbouch, O., 49, 68, 69, 112 Azerbaev, I. N., 86 Babczinski, P., 136 Babkina, E. I., 47, 253 Babyak, A. G., 194 Bach, M., 265 Backer, J. M., 228 Badlev. A. R.. 250 Bahr,“W., 153‘ Bacr, E., 139 Biir, H. P., 149 Ba-glioni, C., 164 Bagshaw, C. R., 154 Bahl, C. P., 160, 161, 269 Baigil’dina, S. Yu., 45 86, 97 Bairamova, N. I., 76 Baitz-Gacs, E., 234 Balitskii. Y. V.. 54 Balykcvi, T. A’, 83 Banacky, P., 250 Banerjee, B., 269 Baranov. G. M., 110 Baraze, A., 125 Rarker, R. W., 138 Barket, T. P., 6 Barketov, E. S., 119, 267 ,I
27 1
Barley, G. C., 182 Barlow, A. J., 265 Barnikow, G., 127 Barrans, J., 24, 35, 42, 98 Barratt, M. D., 250 Barrett, J. C., 161 Barry, C. D., 236 Barsukov L. I., 228 Bartell, L: S., 28, 57, 262 Bartet, B., 25, 69 Barth, D., 212 Bartlett, P. D., 34, 90 Barton, D. H. R., 193 Bartsch, W., 99, 136, 185 Bashirova, L. A., 63, 109 Bastian, V., 200 Batey, I. L., 162 Batyeva, E. S.,37,82,91,126 Bau, R., 209 Baudler, M., 3, 66, 246 Bauer, G., 64, 249,266 Bauer, S., 135 Bauer, V. E., 129 Baumstark, A. L., 34, 90 Bausch, R., 160,241 Bayandina, E. V., 113, 227 Bayer, E., 159 Beasley, G. H., 184 Beauchamp, J. L., 267 Beave, J. A., 152 Becher, H. J., 4 Bechgaard, K., 226 Bechtel, P. J., 152 Becker, K. B., 177 Beckman, J. A., 209 Beeby, P. J., 183 Beeny, M. T., 46 Beevor, P. S., 181 Begley, M. J., 211 Bellet, E. M., 114 Bel’skii, V. E., 128, 230, 246, 250, 264 Belvedere, G., 268 Belyaev, N. N., 171 Belyaev, Yu. P., 204 Benassi, R., 234, 245 Bender, R., 235 Benezra, C., 215, 265 Benkovic, P. A., 142 Benkovic, S. J., 142 Bennett, V., 156 Benschop, H. P., 213 Bensoam, J., 123 Bentley, R. K., 180 Bentrude, W. G.,101, 102, 221, 234., 248, 251 Bcrdcn, J. A., 138, 228 Berdnikov. E. A., 17, 73, 130 Beres, L.. 156 Berezovskii, V. M., 257 Bergelson, L. D., 228 Berger, P. A., 249
272 I3ergeron, C. R., 201 I3ergmann, E. D., 39, 72 I3ergounhou, C., 245 I3erkman, Z. A., 76 I3erlin, K. D., 2, 17, 66, 73, 77, 235, 244, 260 13erman, H. M., 29 13erman, S. T., 235 I3ermann, M., 189 I3ermej0, M. P., 264 I3erna1, I., 219, 247 I3ernard, D., 36, 37, 41, 44, 91, 241 I3ernardi, A., 163 I3ernofsky, C., 132 I3ershas, J. P., 169 13ertazzoni, U., 163 I3ertin, D. M., 264 I3ertina, L. E., 76 13ertrand, R. D., 244 13erwin, H. J., 244 I3esold, R., 169 13esserre, D., 263, 264 I3estmann. H. J.. 166. 169. 170, 171, 174,’ 175,’ 176; 180, 183, 260 Betkouski, M. F., 180 Bewert, W., 188 Beznichenko, V. V., 18;4 Bhagwat, V. M., 119 Bickelhaupt, F., 26, 214, 247, 256 Bidzilya, V. A., 236 Biehl, E. R., 171 Biely, P., 135 Billiau. A.. 163 BindeL H.: 125 Binger; P.,’ 1 Bird, C. W., 85, 225 Biryukov, I. P., 246 Bishop, S. H., 211, 261 Bissell, E. C., 210 Bito. T.. 117 Bitter, W., 196 Bittman, R., 103, 138 Bittner, S., 225 Black, D. St. C., 186 Blackburne, I. D., 234 Blagoveshchenskii, V. S., 105. 106 Blanshard, K. C., 269 Bloch, A. N., 226 Bloomer, J. L., 181 Bobkova, L. I., 195 Bobst, A. M., 165 Bochkarev, V. N., 265 Bodalski, R., 234 Bodrova, M. R., 114 Boekestein, G., 248 Bogdanov, N. N., 110 Bogdanovid, B., 166, 241 Bohm, B., 80 Boigograin, R. A., 12 Boiko, A. P., 107, 195, 196, 203 Bois, M., 236 Bokanov, A. I., 45, 255, 256 Bokarov, E. M., 114 Boldeskul, I. E., 254 Bolduc, P. R., 90, 224 Bone, S. A., 35, 98, 237 Borch, G., 182 Bordner, J., 230
Author Index Bordwell, F. G., 267 Borisenko, A. A., 56, 243 Borisov, G., 80 Borisova, E. E., 41, 83 Borleske, S. G., 67 Boronoeva, T. R., 171 Borovikov, Yu. Ya., 253, 265 Bose, A. K., 13 Bossi, A., 268 Boswell, K. H., 150 Bosyakov, Yu. G., 86 Both, W., 170, 183 Bottcher, W., 2 Bottin-Strzalko, T., 245 Bottomley, R. C., 152 Boudreaux, J. A., 120 Boutin, N. E., 65 Boyce, C. B. C., 46, 222 Boyer, P. D., 139, 140 Brandsma, L., 9 Brandstetter, F., 159 Brauer, D. J., 167 Brault, J. F., 245 Braun, R. W., 30, 239, 240 Bravo, P., 180 Bravo, R., 76 Brazier, J.-F., 41 Brennecke, L., 84, 128 Breuer, E., 186 B rewer, H. B., 228 Brickmann, J., 59, 239 B roadhurst, M. D., 184 Brodelius, P., 152, 269 B roquet, C., 177 Brosz, C. S., 181 B rown, C.. 120 Brownstein, M., 65 Brun, G., 204 Bruniquel, M. F., 25, 257 Bryde, S. B., 261 Brzezinka, H., 182 Buchikhin. E. P.. 268 Buchner, W., 30, 200, 231, 243 Buck, H. M., 9, 39, 220, 234, 248, 249 Buckle, J., 169 Buder, W., 230 Budniok, A., 264 Budzikiewicz, H., 182 Biichi, G., 177 Bugada, R., 246 Bugarenko, E. P., 265 Bugg, C. E., 261 Buina, N. A , 113 Bula, M. J., 76 Bulina, V. M., 180 Bullen, G. J., 211 Bulyanitsa, L. S., 235 Bundgaard, T., 28 Bundle, D. R., 136 Bunnett, J. F., 103, 110, 213 Bunting, W. M., 33, 236 Burd, J. F., 162 Burdon, J., 243 Bureva, N. V., 112 Burg, A. B., 57 Burgada, R., 35, 36, 37, 41, 44, 91, 241, 250 Burger, K., 42, 81, 89, 176 Burgers, P. M. J., 149, 158 Burgis, E., 42 Burmistrova, N. P., 268
Burnaeva, L. A., 51, 92, 108, 126 Burnett, R. M., 133 Burns, F. B., 20 Burr, A. H., 211 Buryan, P., 268 Burzlaff, H., 259, 260 Busby, S. J. W., 165, 228 Butin, B. M., 86 Butler, L. G., 144 Butorina. L. S.. 115 Butsugan, Y., 117 Bykov, V. M., 209 Bykova, T. G., 39,80 Eystrov, V. F., 228 Cabrera, A., 265 Cachapuz-Carrelhas, A., 41 Cadogan, J. I. G., 25, 50, 174, 218, 223, 225 Calas, R., 76 Calhoun, H. P., 207, 261 Callahan, J. J., 129 Callot, H. J., 265 Campbell, B. S., 97, 258 Campbell, I. G. M., 50 Campbell, M. N., 226 Cameron, T. S., 258 Camps, F., 166 Cantor, C. R., 157 Carlisle, C. H., 211 Carlson, R. R., 76 Caron, M. G., 156 Carpino, L. A., 12 Carrell, H. L., 29 Carrik, R., 80, 130, 184, 244 Carroll, P. J., 259 Caruthers, M. H., 163 Carver, J. L., 257 Casas, J. S., 264 Casida, J. E., 114 Cassar, L., 18 Castells, J., 166 Castro, B., 10, 12, 95 Cates, L. A., 114 Caulton, K. G., 210 Cavalieri, L. F., 165 Cavell, R. G., 30, 61, 62, 63, 242 Cazzoli, G., 57 Ceccarelli, G., 65 Centofanti, L. F., 45, 56 Cernia, E., 6 Chabrier, P., 117 Chaloner-Larsson, G., 150 Chan, J. K., 131 Chan, J. L. W., 128 Chan, T. H., 7, 67, 223, 265 Chan, W.-T., 26 Chandra, P., 163 Chang, 1,. L., 34, 101 Chang, S. K., 268 Chapleur, Y., 10, 12 Charache, S., 228 Charbonnel, Y., 24, 35, 42, 98 Charkin, 0. P., 264 Charlton, J. R., 25, 265 Chauvin, Y., 3 Chauzov, V. A., 110 Chen, C. H.-J., 137 Chen, K. S., 222 Chekhun, A. L., 80, 88
273
Author Index Chekunina, L. I., 45, 256 Cherepenko, T. I., 201 Cherkasov, R. A., 73, 106, 253, 254, 256, 264 Chernova, A. V., 251, 256 Chernyshev, E. A., 53, 265 Chheda, K. B., 148 Chia, L. S. Y., 163 Chikvaidze, V. N., 269 Chinault, A X . , 155 Chiron, A., 135Chishti, N. H., 19 Chistokletov, V. N., 49, 84, 263 Chiu, T. M. K., 148 Chlebowski, J. F., 143 Chobanya, V. P., 265 Christensen, L. F., 150 Christiaens, L., 87 Christol, H., 17, 18, 19, 20 Christopher, R. E., 204 Chromv. I.. 264 Chu, F: ‘Y.; 255 Chu, M. Y.,150 Chu, S.-H., 148, 150 Ciotti, M., 133 Clapp, C. H., 120, 158 Clardy, J. C., 259, 260, 261 Clare. P.. 203. 210 Clark, D: T., 256 Clark, P. W., 244 Clark, R. D., 185 Cleland, W. W., 158 Clerc, T., 228 Clin, B., 228 Clipsham, R. M., 196, 250 Cloyd, J. C., 5, 73 Coas, V., 269 Codding, E. G., 255 Coetzee, J. H. J., 235 Cohen, E. A., 242 Coleman, J. E., 143 Collier, J. E., 29, 261 Collins, A. J., 113, 260 Collins, D. J., 111 Collins, K. D., 144 Colowick, S. P., 133 Colussi, A. J., 247 Comer, M. J., 152 Commereuc, D., 3 Conesa, A. P., 204 Constenla, M., 28 Cook, P. D., 148 Cook, T. W., 219 Cook, W. J., 208 Cook, W. T., 247 Cookson, R. C., 50 Coombe, B. G., 172 Cooper, D. B., 120 Cooper, P., 220 Corbel, B., 124 Cordes, A. W., 261 Corey, E. J., 15 Cornell, B. A., 246 Cornus, M., 245,246 Cortes, E., 265 Costa, D. J., 30, 59, 65 Costello, A. J. R., 228 Costisella, R., 80, 84,97, 111, 128 Coto, M. V., 264 Cottam, G. L., 143 Cotton, F. A., 151 Courbis, P., 110, 264
Coutrot, P., 127 Cowan, D. O., 224,226 Cowley, A. H., 30, 239, 240, 242, 257 Cox, A. W., 57,255 Cox, R. H., 236 Cramer, F., 153 Craven, D. B., 152 Creary, X., 103, 110, 213 Cremer, S. E., 30,49, 68,242 Cremlyn, R. J., 107, 122 Crens, P., 46 Cresp, T. M., 183 Cristau, H. J., 17, 18, 19, 20 Croisy, A., 87 Cross, R. J., 227 Cross, R. L., 140 Csopak, H., 143 Cuatrecasas, P., 156 Cullis, P. R., 138, 228 Curstedt, T., 268 Curtis, J. L. S., 244 Daasch, L. W., 266 Dahl, A. R., 58 Dahm, D. J., 224 Daigle, D. J., 7 Dailey, B. P., 229 Dalgleish, W. H., 205 Daly, J. J., 28, 258 Danenberg, K. D., 158 Danion, D., 80, 130, 184,244 Danion-Bougot, R., 80 Dann, P. E., 211 Darling, G. D., 133 Das, S., 205 da Silva, R. R., 212 Dauben, W. G., 177, 184 David, J., 107 Davidenko, N. K., 236 Davidson, A. H., 72 Davies, A. G., 220, 247, 248 Davies, A. P., 13 Davies, D. R., 261 Davies, P., 132 Davis, L. G., 138 Davis, V. C., 186 Dea, P., 148 Dean, C. R. S.,57,220 Dean, P. D. G., 152 De’ath, N. J., 33, 60, 238 de Boer, T., 225 DeBruin, K. E., 113, 130 de Clercq, E., 163 Decorzant, R., 182 de Graaf, H. G., 214, 247 de Haan, J. W., 9 Deics, A., 246 De Jersey, J., 144 De Ketelaere, R. F., 71, 250 Dekleijn, J. P., 26 Deleris, G., 76 de Licastro, S. A., 120 De Luca, G., 223 Demarcq, M., 46 Demay, C., 235 Dembech, P., 245 De Meester, P., 261 Demott, R. P., 128, 255 Demuth, R., 3 Denney, D. B., 33, 34, 36, 60, 82, 101, 106, 237, 238 Denney, D. Z., 33, 34, 36, 60, 82, 237,238
Dennis, R. W., 247 Dentch, J. M., 238 De Rooij, R. E., 269 Derstuganova, K. A., 39, 80 Desideri, P. C., 269 Deugau, K. V., 161 Deutch, J. M., 30, 59 Devillers, J., 245, 246 Devoe, S. V., 23, 24 Dewar, M. J. S., 257 Deyrup, J. A., 180 Dieck, R. L., 206 Dietze, U., 251 Dilbeck, G. A., 2, 17 Dills. W. L.. iun.. 152 Djmfoth, K:,-27, ’28 Ding, J., 223 Distefano, S., 240 Dizdaroglu, M., 165 Dmitriev, V. A., 209 Dmitriev. V. I.. 62 Dmitrieva, G. V., 53 Dmitrieva, N. V., 47, 109 Doak, G. O., 59 Dobbie, R. C., 253 Dobson, C. M., 236 Doel, M., 161 Dogadina, A. V., 62,241,245 Doi, K., 208 Dolenko, G. N., 257 Donelli, M. G., 268 Donskaya, Yu. A., 252, 253, 263, 264 Dormov, J. R., 10, 95 Doroshenko, V. V., 63, 125, 199 Doseva, V., 80 DOW,D. C., 260 Downie, I. M., 12 Drabowicz, J., 98 Drach. B. S.. 78. 79 Draeger, U.,’269 Driiger, M., 259 Dreeskamp, H., 166, 241 Dreher, H., 99 Dreissig, W., 259 Dreux. M.. 123. 127. 225 Driessen, P. B. J., 9 ‘ Druzhinina, T. N., 135 Duda, U. M., 255,265 Dudman, N. P. B., 144 Duff, E., 29, 261 Dufourcq, J., 228 Dulog, L., 24, 54 Dulova, V. I., 268 Dunlap, R. B., 148 Dunogues, J., 76 DuPont, T. J., 16, 265 Durand, M., 76, 234 Durig, J. R., 57, 255 Dun, H., 212 Duschek, C. Z., 116 Dutasta, J. P., 102, 245, 260 Dutkiewicz, J., 208 Dyadin, Yu. A., 70 Dvatlova. N. M., 267 Dison, J.’, 207 Dzhaliashvili, T. A., 269 Dzhundabaev, K. D., 107 Dzyubina, M. A., 117 ’
Easdale, M. C., 204 Ebener, U., 163
Author Index
274 Eber, J. T., 139 Ebert, H.-D., 70 Ebetino, F. F., 225 Eccleston, J. F., 154 Eckes, H., 75, 216 Eckstein, F., 140, 142, 149, 154, 157 Edelstein, S. J., 250 Edlund, B., 141 Edmondson, D. E., 133 Eeckhaut, Z., 71 Efanov, V. A., 268 Efimova, V. D., 94 Egorov, A. S., 201 Egorov, Yu. P., 198, 233, 250, 251. 253. 254. 265 Ehrenberg,' L., 152 Eide, A. I., 21 Eiletz, H., 202 Einig, H., 11, 12, 192 EinsDahr. H. M.. 261 Eiseiberg, F., 137,268 Eisenhut, M., 30, 33, 59, 236. 238 El-Deek, M., 64 Elfimova, I. A., 117 Eliseenkov, V. N., 112 Elkaim. J. C.. 235 El'Natanov, Yu. I., 240 Emoto, T., 87 Emsley, J., 235, 251 Engel, R., 105 Engels, J., 150 England, T. E., 161 Engler, E. M., 227 Engstrom, L., 141 Epstein, J., 129 Erdmann, V. A., 156 Eremich, D., 115 Erni, F., 228 Eryan, M. A., 208 Esenina, E. V., 106 Eto, M., 105 Evangelidou-Tsolis, E., 8, 9, 31 Evans, A. G., 222 Evans, F. E., 228, 245 Evans, J. C., 222 Evans, P. J., 269 Evdakov, V. P., 268 Everse, J., 152 Evin, G., 10, 95 Evstaf'ev, G. I., 70 Evstigneeva, R. P., 180 Evtikhov, Z. L., 33, 97 Ezzell, B. R., 24 '
Faerber, P., 162 Falardeau, E. R., 48, 49 Falcon, J. Z., 209 Farr, F. R., 20, 30, 49, 68 Farrar, W. V., 108 Faucher, J.-P., 204 Faulkner, D. J., 182 Fazliev, D. F., 251 Featherman, S. X., 223 Fedorcsak, I., 152 Fedorov, S. G., 203 Fedoseenko, L. G., 114 Felcht, U., 130 Feldman, I., 228 Fenske, D., 4 Ferraris, J. P., 224
Feshchenko, A. G., 124 Feshchenko, N. G., 49, 71 Fields, A. T., 205 Fields, E. S., 10 Fields, R., 220 Fikus, M., 150 Filby, J. E., 223 Fild, M., 30, 231, 234, 239, 24 1 Filippova, I. G., 52, 268 Filler, R., 9 Finch, A., 57, 220 Finev, E. G., 228 Finke. M.. 222 Finkehbine, J. R., 223 Finnan, J. L., 99, 158 Firmin, J. L., 269 Fischer, G. W., 115 Fischer, R., 1, 57 Fishbein, R., 142 Fisher, T. L., 131 Fitseva, R. G., 268 Fitzgerald, T. J., 228 Flanders, S. D., 173 Flick, W., 196 Fliege, W., 206 Fluck, E., 77, 98, 125, 257 Foa, M., 18 FGlsch, G., 143 Fomin, V. A., 35 Font Freide, 9. J. H. M., 220,249 Ford, B. W., 130 Forner, K., 66 Foss, V. L., 56 Foucaud, A., 13, 95, 173 Francina, A.. 268 Franke, R., 167 Franko-Filipasic, B. R., 206 Fraser, G. W., 113,260 Frearson, M. J., 122 Freedman, L. D., 19, 24, 113, 128, 230, 255 Freeman. B. H., 174 Freeman' G. R.; 261 Freeman: W. J., 24, 200, 234 Frjdland, S. V., 47, 109 Frigerio, A., 268 Frischauf. A. M.. 153 Fritz, G.,'3, 58, 229 F r ~ y e n P., , 173 Frohlich, A., 63 Frolov, Yu. L., 255 Frosch, J. V., 171 Froyen, P., 264 Fuchs, P. L., 22, 177 Fuchs, R., 206 Fuller, H. J., 167 Fukuhara, A., 257 Fukuhara, M., 209 Fukui, M., 174 Fukui. S.. 134 Fukui; T.', 162 Fukumoto, K., 225 Fukuto, J. R., 113 Fukuto, T. R., 260 Fullam. B. W.. 219, 247 Furukawa, Y.,' 148. Furusawa, K., 153 Fuzhekova, A. V., 81 Gabe, E. J., 210 Gabriel, T., 162
Gachkovskii, V. F., 257 Gadian, D. G., 143, 165,228 Gadreau, C., 173 Gassner, M., 141 Gaeta, L. J., 209 Gaffney, B. J., 250 Gagnaire, D., 236 Gaidaniaka. S. N., 195 Gaillard, C.', 163 Gajda, T., 124 Gakis, N., 22, 218 Galayaev, N. N., 133 Gallais. F.. 76 Gamache, R.,165 Gamache, R. W., 266 Gamalci, V. G., 257 Gandio, J. D., 2 Cans, P., 204 Gar, K. A., 114 Gardner, J. E., 208 Gardner, P. J., 57, 220 Gareev. R. D., 41, 83, 90, '
Gassen,'H. G., 162 Gavina, F., 121, 191 Gavrilova, G. M., 241 Gaydou, E. M., 246 Gazizov, M. R., 53 Gazizov, T. K., 37, 85, 111, 125 Gebhardt, D. 0. E., 269 Gee, R. D., 25, 50, 225 Gefter, E. L., 78, 109 Gence, G., 42, 44 Gent, M. P. N., 228 Geoffroy, M., 219, 247, 249 Gerber, A. H., 209 Gerhard. W.. 10. 19 Gerson, 'F., 247 . Getoff, N., 213 Gibson, J. A., 31, 61, 192, 193 Gibson. Q. H., 250 Gielen. J.. 164 Gieren, A'., 89 Gilak, A., 11, 30, 61, 65 Gilham, P. T., 162, 163, 164 Gjlje, J. W., 30, 239, 240,257 Gill. E. N.. 152 Gillam S '161 Gillbrd, l?, 220, 247, 248 Gillen, R. G., 150, 151 GilIespie, P. D., 37, 235 Gilyarov, V. A., 31, 64, 190, 197, 250 Ginet, L., 247, 249 Giniyatullin, R. S., 127 Giongo, G. M., 6 Girfanova, Yu. N., 82 Giziewicz, J., 148 Glasel, J. A., 236 Glaser. S. L., 37, 106 Glass, 'It. S.,'140 Glenxer, Q., 194, 201, 204 Glinka, K., 246 Glonek, T., 138, 154, 228, 229 Gloyna, D., 109, 244 Goe, G. L., 90, 224 Gotz, A., 163
Author Index Gohil R. N., 150 151 Gol’dkarb, E. I., 57, 39, 80, 230 Gol’din, G. S., 209 Goldobov, Yu. G., 108 Gol’dshtein, I. P., 201 Goldwhite, H., 8, 189, 240 Golik, G. A., 201, 253 Golobov, Yu. G., 54, 95, 112 Golyshin, N. M., 114 Gomez Lara, J., 265 Gomi, H., 87, 88 Gompper, R., 184 Gonzalez, G., 125 Goodbrand, H. B., 18 Goodgame, D. M. L., 261 Goodman, D. W., 257 Goodman, H. M., 163 Goody, R. S., 154 Gorbatenko, V. I., 256 Gorbatenko, Zh. K., 49 Gordon, M. D., 57,255,263 Gorenstein, D. G., 165, 232 Gorgues, A., 180 Gorin, P. A. J., 236 Goryunova, I. B., 80 Goryushko, A. G., 236 Gorney, I., 25, 50, 225 Goto, Y., 257 Goubeau, J., 196, 251 Gough, D. A., 132 Gouterman, M., 255 Graaf, H. G., 26 Grachev, M. A., 154 Gramze, R., 105 Grand, A., 245, 260 Granoth, I., 6, 39, 72 Grassberger, M. A., 19, 127 Gratz, J. P., 6 Gray, D. O., 269 Gray, G. A., 20, 30, 49, 68, 242 Gray, R. C., 257 Grayson, M., 18 Grechkin, E. F., 62 Green, C., 228 Greene, G. L., 160 Greenfield, J. C., 132 Greengard, P., 145 Greenwell, P., 157 Gregor, I. K., 266 Gregory, M. J., 119 Grekov, A. P., 114, 254 Gremer, S. E., 20 Grigor’ev, A. I., 267 Grigor’eva, A. A., 267 Griller, D., 221 Grim. S. 0.. 2. 229 Grimm, R.,‘249 Grinberg, S., 225 Grinblat, M. P., 209 Grjndley, T. B., 253 Grishina. 0. N.. 117 Grisley, Dr W., ’245 Gross, B., 10, 12 Gross, H., 80, 84, 97, 111, 128 Gross, K. W., 165 Grosse, J., 60, 232 Grosse-Bowing, W., 202 Grover, A. K., 132 Grozdov, A. G., 209 Gruetzmacher, R. R., 172
275 Gruk, M. P., 39 Grynkiewicz, G., 13, 14, 89 Grzejszczak, S., 183 Grzeskowiak, E., 269 Gubaidullina, R. Sh., 70 Gubnitskaya, E. S., 125 Gudzyk, L. A., 181 Guilford, H., 152 Guilhem, J., 259 Guimaraes, A. C., 102 Gulyaev, N. N., 149, 152 Gumport, R. I., 132 Gupta, R. C., 163 Gurevich, P. A., 45, 86, 97 Guryanova, E. N., 201 Guseva, F. F., 99, 110 Guseva, N. N., 267 Gutfreund, H., 154 Gysegem, P., 189 H aas, A., 193 Haase, J., 263 H aasemann, P., 196 H aegele, G., 95, 231, 236, 241, 266 H aemers, M., 230 H aenel, M. W., 225 H ansel, W., 172 H agen, A. R., 261 H agenberg, L., 162 H agiwara, N., 90 H amauer. G. L.. 208 Harasa, A: F., 201, 209 H aley, B. E., 156 H all, C. D., 33, 60, 238 Hall, D. R., 181 Hall. I. H.. 211. 261 Hall; J. E.,’ 209’ Haller, R., 171 Halmann, M., 136, 213 Hamajima, R., 171 Hamelin, J., 80 Hamer, N. K., 122 Hamilton, S. E., 144 Hamilton, W. C., 29 Hamlet, Z., 187 Hammes, G. G., 132 Hampton, A., 154 Han, H., 134 Hanoune, T., 156 Hansen. M.. 233 Hansen; R. S., 233 Hansske, F., 153 Hantz, A., 254 Hanzawa, Y., 65 Harding, K. E., 183 Harger. M. J. P.. 76, 129, 1$1, 214 Hargittai, I., 262 Hariharan, M., 139 Harkes, A., 13 Harris, C. M., 133 Harris. G. S.. 264 Harris: J. H..’ 95 Harris; R. J.; 157 Harris, R. K., 32, 203, 239, 24 1
Harris, R. M., 24 Harrison, I. T., 171 Harrison, J. M., 120 Harrison, P. G., 169 Hart, D. J., 177 Hartman, J. S., 76
H artmann, A., 73 H arvey, A. J., 148 Harvey, C., 162, 163 H arvey, D. J., 266 H arvey, M. J., 152 H arwood, J. P., 156 H assairi, M., 13, 95 H aszeldine, R. N., 220 H ata, T., 15, 93, 94, 146, 153, 158, 160, H atano, H., 165 H auptmann, H., 24,176,265 H ausen, H. D., 251 H ayashi, H., 174 H ayashi, M., 116, 148, 180 H ayashi, T., 2, 45 H azen, E. E., jun., 151 Healy, J. D., 125 Heaney, H., 12 H earn, M. T. W., 182 Heathcock, C. H., 185 H eavner, G. A., 99, 158, 160 H ebborn, P., 148 H echt, H. J., 259 H echt, S. M., 155 H eckley, P. R., 5, 71 Hedberg, E., 263 H edberg, K., 263 H edberg, L., 263 Hedman, J., 208 H eesing, A,, 19, 90, 192 Heid, E., 171 H eier, K. H., 27, 218 H eil, C. A., 58 H eimann, M., 244 H eimgartner, H., 22, 218 H einman, M., 167 H eitz. W.. 65 H ellef, W;, 246 H ellwinkel, D., 39, 236, 265 H elmbrecht, J., 193 H‘elmreich, E. J. M., 156 H’emminrr. F. W.. 269 H enderson, T. O:, 138, 228 H engstenberg, W., 141 H enning, H.-G., 66, 72, 78, 109, 244 H enry, M., 254 H ensley, P., 250 H erak, J. N., 165 H ercouet, A., 169 H erman, J. C., 228 H‘erriott, A. W., 127 H‘erscovics, A., 136 H es, J., 146 H‘etherington, J. W., 111 H[euschmann. M., 63 H[ewitson, B.; 120 H[ewson, K., 171 H[ickey, K. R., 184 Hlieke. S.. 249 Higashi, F., 103 Higgins, G. M. C., 119 Higham, C. A., 180 Hilbert, C., 116 Hill, K. A., 171 Hill, R. K., 171 Himbert, G., 1, 45, 73 Himmele, W., 206 Hingerty,. B., 261 Hinshaw, W. S., 229 Hirano, Y., 75, 217 Hitchcock. P. B.. 261 Hjelmquist, G., 141
Author Index
276 Ho, C., 228 Hoalla, D., 236 Hobbs, J., 163 Hochberg, A. A., 149 Hochlietner, R., 70 Hocking, M. B., 50 Hodges, H. L., 57 Hogberg, H.-E., 183 Hoelderich, W., 3 Hoffman, P., 237 Hoffman, W. H., 13 Hoffmann, J. F., 156 Hohorst, H. J., 269 Holbrook, S. R., 260 Holderich, W., 58 Holl, P., 42 Holmes, R. R., 29, 59, 233, 237 Holt, E. M., 210 Holt, S. L., 210 Hol9, A., 148, 149 Honda, M., 65 Hong, C. H., 148 Honjo, M., 148 Hoogenraad, N. J., 144 Hopkinson, M. J., 253 Hoppe, J., 150 Horak, A., 154 Horii, I., 208 Horn, H.-G., 201 Horner., L.,_22, 24, 265, _ 255, . 268. Horning, M. G., 266 Horton, D., 190 Hotchkiss, J. C., 243 Hoult, D. I., 138, 165, 228 Howe, R. K., 175, 249 Howell, J. M., 30, 58 Howells, D., 72 Hrivnak, J., 268 Hruska, F. E., 228 H;y,,Y. F., 33, 34,36,60,82, LJ I
H udson. A.. 219. 248 H udson; C.'W., 16 H udson, H. R., 79, 230, 244 H udson, R. F., 120 H unig, S., 166 H uff, L.. 8 H ughes, A. N., 50 H unger, H. D., 269 H unt, G. W., 261 H urwitz, J., 162 H usimi, Y., 153 Huntley, B. G., 20, 25, 265 H[uttner, G., 209 H[utton, W. C., 246 H[wang, H., 20, 49, 68 H[wang, H.-O., 30 Iball. J.. 81. 260 Iguchi, Y . ,'180 Ikeda, S., 134 Ikehara, M., 151, 152, 160, 162
Ikeno. S.. 208 Imazawa,' M., 149 Imsieke, G., 19, 90, 192 Inamota, N., 87, 88, 197,217 Inch, T. D., 120 Indzhikvan. M. G.. 17.' 21 Ingofd, K. U., 221 ' Inokawa, H., 110
Inokawa. S.. 110. 175, 240 Inoue, I.; 166 ' ' Inoue, S., 171 Ionin, B. I., 62, 83, 231, 241, 245
Iriskina, L. B., 48 Isaacs, N. W., 261 Isaacson, Y. A., 103, 138 Isaev, V. L., 225 Ishi, Y., 168, 174 Ishikawa, K., 63 Ishmaeva, E. A., 253, 264 Islamov, R. G., 254 Ismagilova, N. M., 50, 52, 268 Ismailov, V. M., 109 Issleib, K., 2, 3, 5 , 8 Itakura, K., 160, 161, 269 Ito, Y., 223 Itoh, K., 168, 174 Ivancsics, C., 23 Ivanov, B. E., 39, 80, 112, 128, 222, 230, 250, 265 Ivanov, L. L., 180 Ivanova, L. K., 232 Ivanova, N. A., 201 Ivanovics, G., 148 Iwak, S., 181 Izawa, Y., 75, 217 Izmest'ev, I. V., 196, 246 Jachymczyk, W., 135 Jacobus, J., 138 Jacobs, S., 156 Jacquemart, M., 235 Jacquignon, P., 87 Jaeckh, C., 194 Jagodic, V., 251 Jain, S. K., 269 Jain, S. R., 268 Jakobsen, H. J., 28, 233, 234 Janistyn, B., 172 Jansen, E. H. J. M., 248 Janssen, E., 205 Jarvis, B. B., 12 Jasinski, A., 229 Jastorff, B., 148 Javora, P. H., 15 Jeanloz, R. W., 136, 137 Jenkins, J. K., 180 Jenkins, R. N., 19, 24, 113, 230 Jennings, H. J., 136 Jennings, W. B., 243 Jensen, H., 269 Jentzsch, R., 115 Jergil, B., 152 Jesson, J. P., 2 Johannes, B., 182 Johannesen, R. B., 30, 60, 240 John, K.-P., 44, 60, 232 Johnson, D. F., 228 Johnson, D. M., 130 Johnson, G., 226 Johnson, K. F., 253 Johnson, N. P., 258 Johnson, W. D., 251 Jones, C. E., 255 Jones, E. R. H., 180, 182 Jones, R. L., 163 Jones, T. J., 261 Jongsma, C., 26, 247
Jonkers, F. L., 173 Joshua, C. P., 107 Jouany, C., 104 Joubert, J. P., 17, 18 Jovin, T. M., 153 Jugie, G., 104 Jung, A., 105 Junkes, J., 70 Jurczak, J., 13, 14, 89 Jutzi, P., 26 Kaack, H., 253 Kaba, R. A., 221 Kabachnik, M. I., 4, 6, 31, 64, 70, 76, 80, 115, 190, 197, 230, 233, 249, 250, 263, 267 Kaelbe, E. F., 261 Kagan, H., 3 Kajiwara, M., 206, 208 Kakurina, V. P., 34, 35, 50, 24 1 Kalabina, A. V., 62 Kalinchuk, L. N., 268 Kalinin, A. E., 29, 31, 64, 258, 261 Kalir, A., 6, 39, 72 Kallenbach, N. R., 162 Kaluza, G., 134 Kalyagin, G. A., 254 Kametani, T., 225 Kamoshita, K., 117 Kanase, K., 117 Kanter, H., 27 Kanz, H., 20 Kao, J. T., 201 Kaplan, N. O., 133, 152 Kappler, F., 154 Karsch, H. H., 167 Kartoon, I., 225 Kasheva, T. N., 202 Kashimura, N., 190 Kashina, N. V., 254 Kashman, Y., 49,68,69, 12 Kaska, W. C., 7 Kaslow, H. R., 152 Kataev, E. G., 17 Katagiri K 181 Katagiri: N:: 160, 161, 269 Katolichenko, V. I., 253,265 Katritzky, A. R., 234, 253 Katsoyannis. P. G., 139 Katz, R., 228 Kaufman, B. L., 138 Kaufman, R. J., 30, 59, 238 Kaufman, S. J., 165 Kaufmann, G., 26, 162,258 Kawabata, J., 103 Kawai, T., 126 Kawakita, M., 156 Kawamoto, I., 22 Kawamura, H., 208 Kawanisi, M., 125 Kawase, T., 85, 226 Kawashima, T., 197 Kaye, P., 81, 260 Kazakova, N. D., 48 Kazimierczuk, Z., 150 Kaziro, Y., 156 Keat, R., 205, 241 Kees, K., 32, 224 Keith, G., 163 Kelly, S. K., 144 Kelsch, U., 246
277
Author Index Kemp, G., 12 Kendall, D. S., 133 Kennard, O., 72, 259, 261 Kennedy, E. R., 54, 266 Kenney, W. C., 133 Kenyon, G. L., 67, 236 Keough, P. T., 18 Kerekes. I.. 62. 222 Keren-Zur,' M.; 149 Kerr, C. M. L., 247 Khachatryan, R. A., 17, 21 Khairullin, V. K., 53 Khalitov, F. G., 252, 263, 265 Khammatova, Z. M., 129 Khan, A. U., 212 Khan, M. M. T., 5 Khan, W. A., 251 Kharabaev, N. N., 201 Kharrasova, F. M., 94, 231, 253 Khaskin, B. A., 120 Khodak, A. A., 190, 197 Khomutov, R. M., 133 Khomutova, E. D., 257 Khorana, H. G., 162, 163 Khristianovich, D. S., 257 Khurs, E. N., 133 Khusainova, N. G., 73, 130 Kibardin, A. M., 37, 85,125 Kiener, V., 188,201,206,209 Kiiko, N. I., 119 Kikuchi, Y., 193 Killedar, A. V., 119 Kimura. N.. 117 Kimura; T.; 182 King, R. B., 5 , 71, 73 King, T. J., 210, 211 Kinoshita, M., 116, 148 Kinker. K.. 3. 66 Kikhner, C. R., 151 Kireev, V. V., 208, 209 Kireeva, A. Yu., 267 Kirpichnikov, P. A., 246 Kirsanov, A. V., 63, 71, 79, 108, 125, 199 Kirsanova, N. A., 195 Kishore, N., 107 Kita, Y., 178 Kitahara, Y., 223 Kitazawa, E., 15 Kiyokawa, H., 178 Klabuhn, B., 71, 234 Klaebe, A., 41 Klebanskii, A. L., 209 Klein, H. A., 189, 232 Klein, H.-F., 167 Kleiner, H. J., 98, 222 Kleinstuck, R., 65 Kleppe, K., 162 Kleppe, R. K., 162 Kleps, R. A., 154, 228 Klingebiel, U., 194 Kloker, W., 242 Klosowskii, J., 204 Kluba, M., 105 Kluger, R., 120, 128 Klyuchanskaya, S. M., 117 Klyuev, N. A., 115 Knaggs, J. A., 13 Knight, D. W., 180 Knorre, D. G., 158 Knowles, W. S., 7 Knox, K. W., 137
Knunyants, I. L., 225 Kobardin, A. M., 111 Kobayashi, E., 209 Kobayashi, Y., 65 Koch, D., 3, 66 Kocheshkov, K. A., 201 Kochetkov, N. K., 135 Kochetkov, S. N., 152 Kochi, J. K., 222 Kochmann, W., 19 Kobrich, G., 171 Kohler, F. H., 30, 243 Koenig, M., 35, 42, 44 Koppel, H., 109, 244 Koettgen, D., 251 Kogan, V. A., 201 Kohlschein, J., 162 Kojima, H., 90 Kolesnikov, G. S., 209 Kolodka, T. V., 203 Kolodyazhnyi, 0. I., 95, 112 Kolpa, R. L., 259, 261 Konarski, J., 252 Kondo, K., 127, 186 Konieczny, M., 111, 249 Konopka, A., 92, 114,231 Konovalov, E. V., 233 Konovalova, I. V., 34, 35, 50, 51, 83, 88,92, 108, 126, 241, 268 Kopecky, K. R., 223 Kopp, R. W., 192 Kori, S., 180 Kormachev, V. V., 78, 109 Kornoukhova, M. V., 114 Kornuta, P. P., 203 Kornverts, M. Z., 124 Korobchenko, V. A., 52,268 Korolev, B. A., 64 Koroteev, M. P., 84 Korshak, V. V., 208, 209 Korytnyk, W., 133 Kosmatyi, E. S., 269 Kosovtsev, V. V., 49 Koster, J. B., 166, 241 Koster, R., 1 Kostyanovskii, R. G., 240 Kotlarek, W., 124 Kotoguma, T., 208 Koval, V. G., 251, 254 Kovalenko, V. I., 125 Kovaleva, A. S., 180 Kovaleva, T. V., 49 Kovenya, V. A., 194 Kovtun, V. Yu., 250 Kozar, L. G., 185 Kozarich, J. W., 155 Kozlov, E. S., 195 Kozlov, N. S., 83, 257 Kozlov, V. A., 253 Kraemer, R., 114 Kraglov, S. V., 245 Kramer, L., 29 Krapcho, A. P., 173 Krapp, W., 39 Krasnec, L., 250 Krasnoperova, A. A,, 257 Kratz, H., 263 Krawczyk, H., 186 Krawiecka, B., 92 Krebs, B., 196 Krebs, E. G., 152 Kreiter, C. G., 167 Kremelev, M. M., 268
Kremer, P. W., 20, 30,49, 68 Kresse, J., 160 Kricheldorf, H. R., 190 Krilov, D., 165 Krishnamurthy, S. S., 205 Krivosheeva. I. A.. 129 Kroon, A. P:, 125 ' Kroon, P. A., 242 Kroth, H. J., 58, 235 Kriiger, C., 167, 258 Kruger, G., 185 Kruglov, S. V., 83 Krupnov, V. K., 251 Krusic, P. J., 222 Kruski, A. W., 138, 228 Krut'skaya, L. V., 56 Krutskii, L. N., 56 Kryzywanski, J., 118 Kubachnik, M. I., 267 Kubardina, L. K., 85 Kucar, S., 135 Kuchen, W., 109, 231 Kucherova, M. N., 201 Kuczkowski, J. A., 230 Kudinova, V. V., 56 Kudryavtsev, A. B., 255 Kudrvavtsev. B. B.. 78 39, 195, 196. 198. 201. '202.' 203. ' . . 2561.268 . Kukhtin, V. A., 78 Kukushkina, V. S., 70 Kulikowski, T.,162 Kumada. M.. 2.45 Kumadaki, I:, 65 Kuramshin, I. Ya., 252, 253 Kurbatov, V. A., 246 Kuroda, M., 257 Kurshakova, N. A., 33, 97 Kurz, W., 225 Kusov, Y. Y., 135 Kutvrev. G. A..~.73. 106. 254, 256 Kuwajima, T., 145 Kuznetsov, E. V., 71 Kwast-Welfeld, J., 150 Kyandzhetsian, R. A., 168 Kvba. E. P.. 16 Kiker, G. S., 209 Kyuntsel, I. A., 196 Kyuntsel, I. V., 246 ~
Labarre, J. F., 25, 204, 255, 257 Lachmann, B., 133 Lacombe, M.-L., 156 Ladner, D. W., 171 Lafaille, L., 250 Lakharov, V. I., 245 Lal, B., 13 Laliberte, B. R., 208 Lamb, J., 265 Lamed, R., 153, 269 Lamotte, A., 268 Lampen, J. O., 141 Landis, M. E., 34, 90 Lang, R. P., 76 Langford, G. R., 58 Langridge, R., 261 Lanka, E., 157
Author Index Lappi, D. A., 152 Larsson, P.-O., 152, 269 Laseter, A. G., 171 Laskorin, B. N., 88,252,254 Laszkiewicz, B., 208 Latscha, H. P., 189, 232 Laurenco, C., 36 Laurent, J.-P., 76, 104, 234 Laurent’ev, A. N., 268 Lavallee, D. K., 236 Lavielle, G., 116, 123 Lavrinenko-Omecinskaja, E. D., 77, 256 Lawesson, S. O., 125 Lawson, D. F., 206 Layne, P. P., 143 Lazukina, L. A., 47 Lebedev, A. V., 158 Le Coq, A., 180 Le Corre, M., 169, 173, 180 Leder, P., 162, 164 Lee, A. O., 180 Lee, C . H., 228 Lee, C.-Y., 152 Lee, D. P., 10 Lee, J. C., 156 Lee, K.-W., 197 Lee, S., 37, 235 Lee, S. M., 268 Lee, S. O., 233 Lefkowitz, R. J., 156 Leguern, D., 13 Lehypt, M. R., 66 Lehle, L., 136 Lehnert, W., 171 Lehr, W., 204 Leibovici, C., 255 Leicknam, J. P., 254 Leissring, E., 8 Lemke, J. M., 114 Lengyel, P., 157 Leonard, N. J., 132 Lepage, P., 234 Le Pogam, J., 269 Leppert, E., 190 Lepri, L., 269 Lequan, R. M., 243 Le Quesne, M. E., 133 Lerman, C. L., 34, 90 Leroux, Y., 123, 225 Leslie, R. B., 250 Lester, R., 181 Lester, R. L., 137 Letsinger, R. L., 99, 158, 159, 160 Levashov, I. N., 83 Level, M., 135 Levi, I. S., 124 Levin, Ya. A., 222, 265 Levina, A. S., 158 Levy, J. B., 113, 245 Lewandowski, A., 269 Leznoff, C. C., 166 Li, Y. S., 57, 255 Liaaen-Jensen, S., 182 Liao, T.-H., 149 Liberti, P.. 164 Lieb, F., 24, 265 Lienert. J., 171 Ljlja, H., 143 Lillehaur. J. R.. 162 Lin, F., 237 Lin, G. H. Y., 113, 260 Lin, M. C., 156 ‘
Lindberg, B. J., 208 Lindberg, M., 152 Linder, E., 16 Lindman, B., 143 Lindner, E., 70, 99 Lindner, W., 236 Lindstrom, R. H., 207 Lines, E. L.,45, 56 Lingner, U., 259 Liober, B. G., 129 Lipatova, I. P., 117, 254 Lischewski, M., 5 Lisitsa, M. P., 252 Liu, L. Y., 136 Liu, Y., 127 Livramento, J., 165 Llinas, J. R., 246 Lloyd, D., 174, 264 Lo, K. W., 150 Lockwood, R. A., 223 Loginova, E. I., 242 Lomakina, V. I., 114 London, C., 156 Lopatin, S. N., 76 Lopatin, V. M., 201 Lopuzinskii, A., 109 Lorenzo, C., 264 Loseva, I. M., 125 Louw, R., 124 Love, J. L., 209 Lowe, C. R., 152 Luber, J., 31, 64, 203, 232 Lucas-Lenard, J., 156 Lucken, E. A. C., 219, 247, 249
Luckenbach, R., 17, 18, 21, 24, 69, 223, 236, 268 Luckoff, M., 27 Luczak. J.. 69. 114 Ludwii, M.L:, 133 Luedtke, E., 171 Lugovkin, B. P., 80 Lumbroso, H., 264 Lunsford, W. B., 99, 158 Lussan, C., 228 Lutsenko, I. F., 56, 80, 88 Lythgoe, B., 171 M aassen, J. A., 157 M aatschappij, B. V., 5 M acak, J., 268 M acarovici, C. G., 80 M cClellan, G. H., 210 M cClure, D. E., 224 M cConnell, H. M., 250 M acCoss, M., 148 M cCutchan, J. M., 164 M cEwen, G. K., 244 M acFarlane, W., 241 M cGuire, H. M., 171 M clntosh, J. M., 18, 22 M ackie, R. K., 223 M claughlin, A. C., 138, 228 M IcMurry, T. B. H., 63 M jacomber, R. S., 54, 266 M acpherson, A. J., 129 M[cVicker, E. M., 239 M rcWilliam, H. M., 225 Miaekawa. K., 117 Maeno, H., 145 Msrkl, G., 24, 26, 27, 218, 247. 265 hlagdesieva, N. N., 168
Maglothin, J. A., 141 Magnus, P. D., 193 Maguire, J., 140 Mahran, M. R., 81 Maier, L., 7, 63, 229 Maiguma, C., 208 Maijs, L. A., 258 Maikova, A. I., 53 Majoral, J. P., 114, 245 Majumder, A. L., 137, 268 Makarenko, I. M., 268 Makarova, L. I., 209 Makarova, N. A., 232 Makirov, I. Kh., 245 Makovetskii, P. S., 201 Makovetskii, Yu. P., 254 Malakhova, I. G., 6,249,263 Malavaud, C., 35, 98 Malevannaya, R. A., 76, 267 Malisch, W., 168 Malovik, V. V., 71 Mamina, A. I., 50 Manandhar, S. P., 269 Manapov, R. A., 252 Manatt, S. L., 242 Mandel’baum, Yu. A., 114 Mander, L. N., 172 Manel, F. S., 236 Mangold, D., 171 Manhas, M. S., 13 Manning, C., 166 Marapet’yants, M. Kh., 267 Marcati, F., 6 Marchenko, A. P., 124 Marcondes, M. E. R., 214 Marcus, S. L., 165 Marecek, J. F., 29, 37, 42, 106, 232 Mareev, Yu. M., 245 Margulis, B. Ya., 17 Marians, K. J., 161 Markila, P. L., 210 Markowskij, L. N., 62 Marquarding, D., 237 Marquardt, M., 153 Marre, M.-R., 41 Marsi, K. L., 20 Martell, A. E., 5, 139 Martin, C., 27 Martin, D., 174 Martin, D. R., 236 Martin, J., 102, 262 Martin, M. A., 153 Martin, S. F., 169, 184 Martinez-Carrion, M., 133 Martini, A., 268 Martynyuk, A. P., 192, 198, 250, 268 Marumo, S., 181 Maruyama, H., 15 Masaguer Fernandez, J. R., 264 Mashlyakovskii, L. N., 62, 241, 245 Maslennikov, I. G., 268 Mason, R., 261 Masse, G. M., 22 Mastalesz, P., 126 Mastrvukova. T. A.,~. 115, 230,- 267 Mathey, F., 25, 26, 69, 123, 257, 258, 265 Mathis. F.. 35. 114 Mathis; R.; 250 ’
Author Index Matrosov, E. I., 80, 115, 230, 250, 263 Matsubara, T., 139 Matsueda, R., 15 Matsushita, H., 257 Matsuura, H., 175, 240 Matthes, D., 26 Matthews, W. S., 267 Matveev, I. S., 229 Matzinger, D., 15, 226 Mavel, G., 229 Maya, L., 57 Mayeline, C., 219 Mayhew, S. G., 133 Mazalov, L. N., 257 Mazeling, C., 247 Mazepa, 1. K., 71 Mazurek. M., 236 Mazzola,’ E., 240 Meakin, P., 222 Mebazaa, M. H., 235 Medved, T. Y., 4, 80 Medvedev. V. I.. 268 Meek, D. k.,76 Meffert. A.. 81. 176 Meijer,‘J., 9 Mellor, M. T. J., 20 Mel’nichenko, N. V., 256 Melnick, R.-L,., 140 Mel’nikov, N. N., 120 Melvin. L. S.. 15 M enke; A. G:, 266 M erkulov, A. V., 109 Mertes, M. P., 146 M etzler, D. E., 133 M eyer, R. B. jun., 148, 150 M hala, M. M., 119 M ian, A. M., 148 M ichalewsky, J., 162 M ichalski, J., 92, 107 M ichalski, J. M., 109 M ichell, R. H., 137 M ichels, R., 65 M ickey, C. D., 15 M iddleton, L. C., 25, 265 M iddleton. T. R., 251 Midura, W., 183 Miesel, J. L., 122 Miftakhova, A. K., 76 Migeon, M., 253 Mikami, N., 214 Mikhailichenko, A. I., 267 Mikolajczyk, M., 69, 92, 98, 114, 118, 183 Miles J. A., 46 Miles: M. G., 224 Milicev, S., 251 Milker, R., 11, 189 Millar, J. A., 260 Millar, K., 258 Miller, J. A., 51, 81 Miller, J. G., 225 Miller. J. P.. 150 Miller; J. S.; 210 Miller P. S., 161 Millinbton, D., 211, 227 M!lls, J. L., 16, 229, 265 Milnes. D. R.. 122 Minarni, T., 23, 184 Mingaleva, K. S., 263 Mironova, Z. N., 70 Mishchenko, V. V., 257 Mishra, S. P., 219, 247 Mislow, K., 25
279 Mitchell, H. L., 30, 59, 238 Mitchell, P., 139 Mittelman, A., 148 Miura, K., 149 Miyamoto, T., 178, 180 Miyashita, O., 148 Miyashi, Y., 117 Mizutani, M., 92 Mlotkowska, B., 80, 107 Modak, M. J., 165 Modro, T., 127 Moedritzer, K., 54, 235, 266 Moller, W., 157 Mohamed, M., 64 Mohr, K., 3 Mokeeva, V. A., 196, 246 Molenda, R. P., 2, 229 Momsen, W., 140 Monson, R. S., 125 Montemayor, R. G., 56 Montgomery, J. A., 171 Moody, D. C., 5 8 Moon, R. R., 229 Moore. G. Y.. 208 Mootz; D., 59, 261 Morel, G., 13 Morgan. G. G., 250 Moritani, I., 10 Morris, D. L., 2, 17, 73 Morse, J. G., 48,49, 220,241 Mcrse. K. W.., 48,. 49,, 220,. 241 ‘ Morton, J. R.,247 Mosbach, K., 132, 152, 269 Mosbo. J. A.. 260 Mosebkh, R:, 39 Moshchitskii, S. D., 112 Moskal, M., 106 Moskva, V. V., 53, 63, 109, 111 Motekaitis, R. J., 139 Motherwell, W. D. S., 261 Mukaiyama, T., 15 Mukhametov, F. S., 254 Mukmenev, E. T., 232, 264 Muller, B., 184 Mulliez, M., 116 Mumford, C., 223 Muneyama, K., 150 Mungall, W. S., 160 Munoz, A., 35, 42, 44 Murahashi, S.-I., 10 Muramatsu, S., 22 Muratova, A. A., 252 Mushika, Y., 116, 146 Musierowicz, S., 186 Musina. A. A., 39, 83 Muto, M., 117 Mychajlowskij, W., 187 Myers, T. C., 138, 154, 228 Naberezhnova, N. N., 128 Nabi, S. N., 204, 206, 268 Naf, F., 182 Nagakawa, I., 160 Nagpal, K. L., 160 Nagura, T., 152 Nagyvary, J., 148, 150, 151, 160 Nair, I?. G., 107 Nair, P. M., 119 Najjar, V. A., 143 Nakada, Y., 160
Nakagawa, l., 15 Nakayama, S., 217 Nambiar, P. R., 268 Narang, S. A., 160, 161, 269 Narayanan, P., 89 Nasakin, 0. E., 78 Nassimbeni, L., 259 Nassimbeni, L. R., 72 Nasybullina, Z. A., 73, 130 Nath, K., 162 Naumov, V. A., 246, 262 Navalgand, R., 250 Navech, J., 114, 245, 246 Naylor, R. A., 4, 69 Nechitailo, N. A., 117 Neff, J. R., 172 Negishi, A., 186 Neidlein, R.,39 Neilson, T., 161 Nekvasil, J., 268 Nemura, H., 80 Nesbitt, B. F., 181 Nesmeyanov, N. A., 235 Nesterenko, L. I., 53 Nesterenko, V. D., 37, 91, 126 Nesterova, L. I., 108 Nesterova, M. V., 152 Nesterova, N. P., 4 Neszmelyi, A., 234 Neubauer, L., 255, 263 Neumann, H., 145 Neuzil, E., 269 Newton, M. G., 20, 29, 30, 49, 68, 97, 258, 261 Nguyen, X. T., 182 Nicolaides, D. N., 183 Nicolaou, K. C., 15 Niclas, H. J., 174 Niecke, E., 188, 196 Nielsen, H., 269 Niendorf, K., 76 Nierlich F 24 54 Nifant’ev, g. E.: 84, 105, 106, 264 Niitsu, M., 76 Niki, I., 184 Nikitina, G. S., 209 Nikitina, L. V., 267 Nikolaev, A. V., 70 Nikolaev, N. F., 204 Nikonova, L. Z., 99, 110 Nikoronov, K. V., 70 Ninomiya, K., 124 Nishikawa, S., 152 Nishiwaki, T., 21 Nishiyama, H., 168 Nishizawa, Y., 117 Niwano, N., 103 Nomura, Y.,193 Nordlander, J. E., 172 Norman, A. D., 58 Normand, F. L., 7 Normant, H., 123 Norris, R. K., 193 Norval, S., 235 Novikov, V. F., 268 Novzuzov, S. A., 109 Noyes, R. M., 214 Nunn, A. .I., 225 Nuretdinov, I. A., 113, 227, 242,246 Nuretdinova, 0. N., 99, 110, 235
Author Index
280 Nurtdinov, S. Kh., 50, 52, 70, 268 Nwe, K. T., 67, 265 Oakley, R. T., 207 Oberhammer, H., 263 O’Connor, E. M., 15, 226 Oda, M., 223 Odajima, K., 149 Odom, H. C. iun.. 171 Odom; J. D., 38 ’ Oehme, H., 8 Ofitserova, E. K., 34, 88 Ogata, I., 2 Ogata, T., 110, 175, 240 Ogata, Y., 92 Ogilvie, K. K., 228 Ohashi, S., 268 Ohkawa, H., 214 Ohloff. .G., 182 Ohnishi. T.. 168 Ohsawa; A.’, 65 Ohta, M., 208 Ohtsuka, E., 152, 160 Oka, T., 255 Okada, S., 153 Okada, T., 47, 222 Okamoto, Y., 47, 117, 126, 337
ALL.
Okazaki, R., 87, 217 Okonogi, T., 166 Okukado, N., 182 Olah, G. A., 62,222 Olsen. K.. 162. 163 Omelanczuk. J.. 92. 98 Ong, B. S., 7 Oplatka, A.. 153, 269 Orban, M., 235 Orlov, M., 115 Orlov. N. F.. 138 Orwoll, E. F:, 209 Osipov, 0. A., 71, 201 Ostanina, L. P., 53 Ottinger, R., 230 Ovakimyan, A. M., 17 Ovakimyan, M. Z., 21 Ovchinnikov, V. V., 253,264 Overman, J. D., 15, 226 Overman, L. E., 15, 226 Ozawa, S., 209 I
,
Pacakova, V., 268 Packer, L., 140 Paddock, N. L., 66,203,207 Padolina, M. C., 257 Paetzold. R.. 76 Pak, V. D., 83, 257 Palladino, N., 6 Pan, Y.- C. E., 165 Panattoni, C., 223 Panet, A., 162 Pantarotta. C.. 268 Pantzer, R:, 251 Parigam, J. P., 124 Parrott. M. J., 220, 248 Parry, R. W., 56, 192 Panhcill. G. W.. 57 Pashina,’ Yu. N:, 201, 206 Pashinkin, A. P., 37, 125 Pastukhova, I. V., 110 Patchornik, A., 147, 212 Patel, V. C., 206 Patel, V. V., 227
Pattenden, G., 180, 182 Patzelt, R., 156 Pads, H., 156 Paulsen, H., 86, 99, 136, 185 Pavlov, V. A., 129 Pawlak, M., 177 Payen, E., 253 Payling, D. W., 57, 220 Peake, S. C., 30, 60, 240 Pecker, F., 156 Pederson, E. B., 125 Peiffer, G., 110, 264 Pellegrini, M., 157 Pemberton, R. E., 164 Pen’kovskii, V. V., 198, 250 Penkovsky, V. V., 77, 256 Peppard, D. J., 184 Pepperman, A. B., 7 Perahia, D., 228 Perekalin, V. V., 110 Pereyaslova, D. G., 184 Perkins, P. G., 113, 204, 260 Perlman, R. L., 144 Perlstein, J. H., 224 Perozzi, E., 26 Perrin, D. E., 113 Pescia, A., 65 Pesnelle, P., 184 Pesotskaya, G. V., 47 Peter, G., 269 Petov, G. M., 263 Petrashenko, A. A., 267 Petrov, A. A., 33, 39, 62, 83, 84, 97, 171, 231, 245, 263 Petrov, K. A., 110 Petrovskaya, L. I., 76, 267 Petrovskii, P. V., 230, 235 Pfeuffer, T., 156 Pfleiderer, G., 131 Pfleiderer, W., 150 Pfohl, S., 174, 237 Philipp, M., 159 Phillips, L., 46, 222 Phillips, W. G., 82 Pickering, D., 129 Piechucki, C., 183 Piekos, A., 127 Pietrusiewicz, K., 234 Pilot, J. F., 8, 232 Pinchuk, A. M., 49, 124, 194 Plnder, A. R., 171 Pivovarov, M. D., 71 Platonov, V. G.. 225 Plattner, G., 247 Pless, R. C., 159 Plieninger, H., 171 Plieth. K.. 259 Plyashkevich, Yu. G., 255 Pobedimskii, D. G., 246 Podder, S. K., 250 Podesta, R., 120 Pohl, H. H., 27, 28 Pohl, S., 196 Pohleman. H.. 209 Polezhaeva, N. A., 29, 39, 83, 232 Polikarpov, Yu. M., 4 Polivanov, A. N., 265 Polozova. G. I.. 39. 83 Polyakov; V. A:, 228 Pominov, I. S., 254 Pommeret-Chasle, M. F., 13, 95
Pongs, O., 157
Pope, J. M., 246 Popescu, R., 250 Popilin, V. P., 209 Popovici, N., 254 Poppi, R. G., 181 Porte, A. L., 205 Portnoy, N. A., 230 Potekhina, M. I., 117 Potter. K., 150 Potthast, K., 269 Potti, P. P. G., 133 Pouet, M. J., 243, 245 Poulin, D. D., 30,61,62,242 Poulton. G. A.. 63 Powell, G. L., 138 Powers, G. J., 163 Pozhidaev, V. M., 83 Prasad, V. A. V., 42, 232 Predvoditelev, D. A., 264 Preobrazhenskaya, M. N., 124 Prescott, B., 165 Prestegard, J. H., 228 Preston, K. F., 247 Prokof’ev, A. I., 249 Prons, V., 209 Proskurnina, M. V., 80, 88 Pudovik, A. N., 34, 35, 37, 50, 51, 70, 73, 82, 83, 85, 88, 90, 91, 92, 106, 108, 111, 125, 126, 130, 232, 241, 252, 253, 254, 256, 264, 268 Pudovik, M. A., 85, 232 Pulfer, J. D., 196, 250 Pullman, B., 228 Puntervold, O., 182 Purdum, W. R., 2, 66, 77, 235,244 Purich, D. L., 141 Pyatnova, Y. B., 180 Quast, H., 63 Quin, L. D., 6, 16, 57, 67, 139,233,234 Raae, A. J., 162 Radda, G. K., 138, 143, 165,228, 250 Radeglia, R., 230 Radics, L., 234 Raevskaya, 0. E., 254 Raevskii, 0. A,, 252, 253, 263, 264, 265 Rafikov, S. R., 48 Raigorodskii, I. M., 209 Rakhimova, G. I., 231 Rakova, L. V., 34 Raleigh, J. A., 165, 223 Ralko, N. E., 252 Ramachandran, B. V., 119 Ramage, R., 19 Raman, C. V., 76 Ramani, G., 148 Ramirez, F.,8, 9, 29, 31, 37, 42, 106, 219,232,235,237, 247 Ramseyer, J., 152 Randall. G. A.. 163 Randerkh, E., -163 Randerath, K., 163 Ranganthan, T. N., 207 Rao, K. N. 255
Author Index Rao, Y. S., 9 Rapaport, E., 163 Ratovskii, G. V., 255 Ratts, K. W., 46, 82 Rauk, A., 25 Ray, W. J. jun., 142 Razumov, A. I., 45, 53, 63, 86, 97, 109, 111, 129 Razumova, N. A., 33, 39,97 Read, D. iM.,234 Rebek, J., 121, 191 Redmore, D., 82 Rees, D. C., 137 Rees, R. G., 244 Reese, C. B., 149, 158 Reetz, K.-P., 198 Reeves, P. C., 171 Regen, S. L., 10 Regitz, M., 1,45,73,75, 130, 216 Reinbothe, H., 269 Reiss, J. G., 59, 65 Reisse, J., 230 Reith, B. A., 168 Remizov, A. B., 251, 252, 253 Rengan, S. K., 250 Renner, R., 62, 222 Rensen, M., 87 Renzi, G., 223 Repina, L. A., 95, 112 Reynard, K. A., 208,209 Rezvukhin. A. I..~. 158, 228 Ricca, A., 180 Ricci, J. S. jun., 29 Richard, H., 228 Richards, J. H., 229 Richards. R. E.. 138. 143, 165, 228 Richardson, D. I., 142 Richter, D., 156 Riesel, L., 188, 194 Riess, J. G., 30, 235 Rizpolozhenskii, N. I., 254 Roach, M. C., 156 Robas. V. I.. 235 Robbins, J. b., 177 Robert, D. U., 30, 59 Robert, J. B., 102, 236, 241, 245, 260, 262 Roberts. B. P.. 220. 247. 248 Roberts; J. C.; 79, 230 ‘ Roberts, P. J., 167,258 Robertson, A. J. B., 235 Robinet, G., 255 Robins, M. J., 148 Robins, R. K., 148, 150 Rodbell, M., 156 Roesch, L., 58, 235, 251 Roschenthaler, G.-V., 31, 188, 193 Roesky, H. W., 202, 205, 242 Roessel, K., 251 Romanov, G. V., 268 Ronen-Braunstein, I., 186 Roschenthaler, G.-V., 61 Rose, H., 206 Rose, S. H., 208, 209 Rosenthal, A. F., 103, 138 Roser, C. E., 16 Ross, B., 198 Rossi, A. R., 30, 58 Rossknecht, H., 201
28 1 Rosswag, N., 204 Rothius, R., 220, 249 Rouiller, M., 182 Rouse, J. P., 151 Rousseau, R. J., 148 Roussel, J., 246 ROUX,E., 254 Rowell, F. J., 225 Rowley, A., 225 Rozanel’skaya, N. A., 255 Rozinov, V. G., 255 Rubchinskaya, Yu. M., 257 Rubinstein, M., 147, 242 Rudavskii, V. P., 201 Rudenko, L. P., 201 Riifenacht, K., 106 Ruff. J. K.. 189 Ruppert, I.; 30, 61, 189, 199, 200,210 Rusak, A. F., 228 Russegger, P., 59, 239 Rysfll, D. R., 29, 113, 260, Ruveda. M. A.. 120 Ryabokon, G. ‘M., 209 Rycroft, D. S., 241 Ryl’tsev, E. V., 251, 254 Rymareva, T. G., 120 Ryschka, W., 171 Sabacky, M. J., 7 Sacher, M., 213 Sacher, R. E., 208 Sadovskii, A. P., 257 Sadoyama, K., 80 Saenger, W., 142 Saeling, G., 127 Saheki, K., 117 Saito, H., 206 Saito, T., 181 Saksena, A. K., 171 Sakurai, H., 47,117,126,222 Salakhutdinov, R. A., 45, 63, 94, 97, 109, 111, 231 Salomon, Y., 156 Samaan, S., 22 Samarai, L. I., 256 Samitov, Yu. Yu., 50, 241, 246 Samoilenko, G. V., 115 Samurina, S. V., 112 Sanakoeva, S. A., 107 Sanchez, M., 35, 236 Sandmann, H., 246 Sandmeier, D., 169, 175 Sanin, P. I., 117 Sanz, F., 28, 258 Saran, A., 228 Sargent, M. V., 183 Sarma, R. H., 228,245 Sartaniya, V. G., 209 Sartori, P., 70 Sasisekharan, V., 261 Sasson, Y., 49, 70, 104, 198 Sato, H., 127 Sato, T., 261 Sau. A. C.. 205
Savoskina, G. P., 235 Savushkina, V. I., 53
Sayer, P., 255 Scanlan, I. W., 256 Scanu, A. M., 138, 228 Scott, R. J., 25, 50, 174, 218, 225 Schaap, A. P., 32, 224 Schadow, H., 207 Schaefer, H., 3, 58, 229 Schaefer, W., 256 Schaffer, Q., 28 Schaible, B., 251 Scharf. B.. 209 Schattka, K.,148 Scheffler, K., 249 Scheit, K. H., 150, 154, 162 Scheler, H., 207 Schenetti. M. L.. 234. 245 Schep, R: A., 235 ’ Scherer, 0. J., 190, 191 Scherowsky, G., 226 Schiebel, H.-M., 32 Schiemenz, G. P., 253 Schilling, P., 62, 222 Schipper, P., 9 Schlak, 0..32, 266 Schleich, T., 258 Schlientz, W. J., 189 Schlosser, M., 212 Schlube, H., 180 Schmalz, D., 171 Schmid, G., 175, 176 Schmid, H., 22, 218 Schmidbaur, H., 30, 97, 166,167,168,243,244,251 Schmidpeter, A., 31, 64, 201, 202, 203, 232 Schmidt, A., 171, 230 Schmidt, M. F. G., 134 Schmidtberg, G., 266 Schmutzler, R., 30, 32, 44, 59, 60, 65, 188, 192, 232, 240, 261, 266 Schneider, N. S., 208 Schnell, A., 19 Schoenberg, A., 178 Schoning, G., 194 Scholtissek, C., 134 Schoner, W., 156 Schott, H., 159, 269 Schoufs, M., 9 Schow, S., 189 Schramm, M., 156 Schray, K. J., 142 Schrecker, O., 141 Schroderheim, G., 208 Schiitz, H., 159 Schukina, L. I., 127 Schulte, K. W., 256 Schulte-Frohlinde, D., 165 Schultz, C. W., 192 Schultz, G. Y., 262 Schulze-Pannier, H., 178 Schumacher. R. J.. 184 Schumann, ‘H., 1, 57, 58, 235, 251 Schwarz, R. T., 134 Schwarz. W.. 209 Schwarzenbach, D.. 182 Schweig, A,, 256 ‘ Schweiger, J. R., 242, 257 Schweizer, E. E., 23, 24, 200. 234 Schwendeman, R. H., 255 Searle, H. T., 207
Author Index
282 Sears, B., 246 Seaver, S. S., 144 Seeley, P. J., 165, 228 Segall, Y., 6, 39, 72, 268 Sekine, M., 15, 93, 94, 146, 153. 158 Sekine, T., 76 Seliger, H., 159 Sellstedt, J. H., 184 Selve, C., 10, 12, 95 Selvoski, M. A,, 206 Semenii, V. Ya., 71, 195, 251, 254, 265 Seno, M., 257 Serdyukova, A. V., 110 Sergeev, G. B., 228, 235 Sergeev, N. M., 243 Sergienko, L. M., 255 Serreqi, J., 203 Sersen, F., 250 Seshadri, T. P., 261 Severin, E. S., 133, 152 Shafigullina, R. D., 94 Shagidullin, R. R., 250, 251, 254, 256 Shahak, I., 70, 104, 198 Shalyudina, 0. S., 232 Shamak, I., 49 Shandruk, M. I., 114, 254 Shapiro, T. A., 257 Shapiro, Yu. E., 228 Shar, V. V., 117 Sharapov, 33. N., 254 Sharma, C. B., 136 Shaturskii, Ya. P., 78 Shaw, R. A., 125, 204, 205, 206, 268 Shcherbina, T. M., 115 Shears, M. F., 265 Sheinkman, A. K., 115 Sheldrick, W. S., 44, 60, 232 Shepherd, R., 259 Shepherd, R. G., 72 Sheppard, D., 222 Shermergorn, I. M., 41, 83 Sherry, A. D., 143 Shibaev, V. N., 135 Shibzta, A., 257 Shih, T. Y., 153 Shikhmuratova, D. V., 52, 268 Shimada, Y., 147 Shimokawa, K., 152 Shinohara, I., 208 Shioiri, T., 124 Shipley, G. G. 261 Shiranov, D. F., 201 Shiue, C.-Y., 148, 150 Shokol, V. A., 201, 236 Short, S. A., 138 Shtepanek, A. S., 268 Shugar, D., 148, 150, 162 Shulyndina, 0. S., 106 Shuman, D. A., 150 Shuto, Y., 117 Shvets, A. A., 71 Sibatulina, F. G., 113 Sicka, R. W., 209 Sidky, M. M., 81 Sidorenko, V. V., 267 Sjdwell, .R. W., 148 Siedlecki, J. A., 162 Sewers, I. J., 142 Silvon, M. P., 173
Simon, L.N., 148, 150 Simoncsits, A., 152, 156 Simonnin, M. P., 243, 245 Simons, S. S. jun., 119 Simonson, L. P., 149 Simonyan, A. A., 21 Simpson, P., 117 Simpson, R. T., 144 Singer, E., 178 Singer, L. A., 197 Singer, T. P., 133 Singler, R. E., 208 Sinha, T. K., 165 Sitdikova, T. Sh., 63, 111 Sivarajan, M., 163 Sjovall, J., 268 Sklenskaya, E. V., 267 Sklyarskii, L. S., 105 Skobun, A. S., 86, 112 Skowronska, A., 92, 107 Skvortzov, N. K., 231 Slabaugh, M. R., 148 Slesar, L. N., 138 Sleziona, J., 46 Small, D. A. P., 152 Smeltz, K. M., 208 Smith, B. C., 125, 205 Smith, C. P., 8, 232 Smith, D. G., 21 Smith, D. J. M., 20, 21, 53, 70 Smith, L. R., 16, 229, 265 Smith, M., 161 Smith, R. J. M., 228 Smith, S. W., 137 Smith, W. M., 133 Smrt, J., 152, 158 Snider, T. E., 2 Snieckus, V., 184 Snyder, D. L., 201 Sobanov, A. A., 130,254 Sochilin, E. G., 268 SOH, D., 163, 164 Soercnsen, S., 233, 234 Soifer, G. B., 196, 246 Sokal’skaya, L. I., S8, 252 Sokoloski, E. A., 228 Sokolovsky, M., 145 Sokurenko, A. S., 105 Soleiman, M., 18, 19, 20 Solodushchenko, G. F., 195 Solodushenkov, S. N., 267 Solofovnikov, S. P., 249 Sologub, L. S., 112 So!ymosy, F., 152 Somieski, R., 188, 194 Sondheimer, F., 183 Sonnenschein, FI., 3 Sonnet, P. E., 170, 181 SoDori. M.. 157 So;do,’J., 264 Soroka, M., 126 Sosnovsky, G., 1 1 1, 249 Sovokina. S. F.. 106 Sowerby, D. B.,‘203,210,211 Sperow, J. W., 144 Spiegel, A. M., 156 Spivak, L. L., 267 Sprangers, W. J. J., 124 Sprinzl, M., 153, 156 Stadnichuk, M. D., 171 Staley, R. H., 267 Stanislowski, A. G., 151 Stankiewicz, T., 30, 231
Stark, G. R.. 144. 206. 209 Stec, w., 109 Stec, W. J., 92, 93, 114, 227, 231, 242 Steffens, J. J., 142 Steger, E., 204 Stegmann, H. B., 64, 249 Stehlik. D.. 141 Stein. M. T.. 210 Stein; R., 141 Steinberger, H., 109, 231 Stellman, S. D., 261 Stemmler, I., 166 Steuanek. A. S.. 198. 199 Stepanoc B. 1.,’45, 201, 206, 255, 256 Stepanov, I. A., 84 Stephenson, L. M., 224 Sterlin, R. N., 225 Stern, P., 37, 106, 235 Stern, R., 3 Sternbach, H., 157 Sternglanz, H., 261 Stevens, J. D., 151 Stocks, R. C., 234 Stoll, H., 251 Stookalo, E. A., 62 Stoops, J. K., 144 Storer, R., 182 Stork, G., 225 Stotter, P. L., 171 Stout, M. G., 148 Stransky, W., 166 Strating, J., 168 Stratton, C., 204 Straughan, B. P., 253 Streeter. D. G., 148 Strich, A., 59 Strominger, J. L., 136, 137 Struchkov, Yu. T., 29, 31, 64. 258. 261 Strupczewski, J. T., 181 Struszczyk, H., 208 Stuehler, H., 251 Stutz, A:, 154 Stukalo, E. A., 63, 125 Sturner, D., 249 Sturtz. G.. 124 Stutz, ‘PI.. ’78 su, L. s.; 57 Subbotina, L. S., 268 Subrahmanyam, D., 269 Subranianian, E., 261 Suck. D.. 142 Sudakova. E. V.. 138 Sudakova; T. Mi, 70 Sudarev, Yu. I., 125 Sudheendra-Rzo, M. N., 205 Sudol, T., 93, 227 Suerbaev. Kh. A.. 230 Sukhi, L.; 138 ’ Sultanova, D. B., 53 Sultanova, R. B., 52, 70, 268 Sundaralingam, M., 228 Sundaram, P. V., 153 Sundermever. W.. 194 Suter, C., -184 Suzuki, P., 171 Sventitskii, E. N., 235 Sviridov. E. P.. 78. 79 Swan, J. M., 111 Swartz, W. E., 257 Swyke, C., 189 Swyrd, E. A., 144 ‘
‘
’
Author Index SY,J., 156 Symons, M. C . R.,219, 222, 247, 248 Symons, R. H., 157 Szabo, K. jun., 245 Szab6. L.. 135 Szeto,’K. ’S.,163 Taborsky, G., 141 Tack, R. D., 122 Taddei, F., 234, 245 Tagaki, W., 166 Tamchi. Y..116. 146 Taieb, M.,245 ’ Takahagi, H., 15 Takahashi, N., 90 Takaku, H., 147 Takamizawa, A., 127 Takehana, Y., 257 Takeshi, G., 110 Takeuchi, Y.,174,193 Tamm, L. A., 263 Tamura, Y., 178, 180 Tan, H. W., 101, 102, 221, 234,248
Tanabe, S., 153 Tanaka, M., 2 Tanaka, S., 160 Tanigawa, Y.,10 Taniguchi, E., 117 Taniguchi, H., 180 Tanner, W., 136 Tanswell, P., 157 Tantasheva, F. R., 17 Taran, L. B., 107 Tarzivolova, T. A., 129 Tasaka, A., 201 Tavares de Sousa, J., 140 Taylor, E. C., 169 Taylor, R. C., 236 Tebby, J. C., 19 Teichmann, H., 10, 19, 65, 78, 230
Telegin, G. F., 209 Telkova, I. B., 209 Temyachev, I. D., 246 Terao, J., 223 Terebenina, A., 80 Terent’eva, S. A., 232 Tesche. N.. 136 Tezuka, T.; 152 Thakur, C. P., 125 Thaller, V., 180, 182 Thasitis, A., 16 Thavard. D.. 25. 69 Thayer, A. L., 32, 224 The, K. I., 30, 63 Thenn, W., 89 Thibaut, Ph., 87 Tho, N. D., 215 Thomas, A. J., 269 Thomas, B., 207 Thomas, G. J. jun., 165 Thomas, K. M., 261 Thomas, L. C., 250 Thomas, M. G., 192 Thommen, W., 182 Thompson, B. C., 143 Thompson, T. E., 246 Thulin, B., 183 Thuong, N. T., 117 Tikhonina, N. A., 31, 64 Tikhonova, L. I., 80
283 Tilichenko, M. N., 86, 112 Tillott. R. J.. 211 Timofeeva, G. I., 31, 64 Timokhin, B. V., 62 Timoshina, T. V., 73, 130 Titus. D. D.. 259 Tkacz, J. S.,’136 Toch, P. L., 208, 266 Tochilkina, L. M., 199 Todd, S. M., 207 Todhunter, J. A,, 141 Tolkechev, V. N., 124 Tollin, P., 261 Tolls, E., 3, 66 Tolman, C. A., 2 Tomasz, J., 152, 156 Tomioka, H., 75, 217 Tong, D. A., 205 Tong, W. P., 12 Topsom, R. D., 253 Torgerson, D. F., 57 Toriolo, L., 223 Toropova, V. F., 76 Torrence, P. F., 163 Toscano, V. G., 212, 214 Traficante, D. D., 30,59,238 Trayer, H. R., 152 Trayer, I. P., 152 Trentham. D. R.. 154 Triantaphylides, C., 136 Trigalo, F., 135 Trippett, S, 20, 29, 35, 53, 70,.98, 237, 261
Tnshin, Y.G., 49 Tritsch, G. L., 148 Trizno. M. S.. 204 Trofimov, B. A., 241 Trommer, W. E., 131 Tronchet, J., 182 Tronchet, J. M. J., 182 Troquet, M., 263, 264 Trotter, J., 210, 261 Troup, G. J. F., 246 Troy, F. A., 136 Trutneva, E. K., 222 Trutneva, E. P., 254 Tsay, Y.-H., 167 Tseng, C.-Y., 183 Tsivunin, V. S., 50, 52, 56, 70. 268
T’so; P. 0. P., 161, 162 Tsoliz, E. E., 232 Tsou, .K. C., 150, 162 Tsuchida, H., 209 Tsuchiva. S.. 257 Tsvetkb4 E: N., 6, 70, 76, 249, 252, 263, 267
Tucker, A. N., 138 Tucker, P. A., 210 Tucker, P. W., 151 Tuemmler, W. B., 209 Tukov, G. V., 268 Tunemoto, D., 127, 186 Turner, J. V., 172 Tusek, L., 251 Tuzova, L. L., 262 Tverskaya, B. M., 269 Uchic, J. T., 160 Ueda, T., 149 Uesugi, S., 152, 162 Ufimtseva, L. I., 53 Ugi, I., 29, 37, 235, 237
Uhlenbeck, O., 161 Uijttewaal, A. P., 173 U1-Hasan, M., 205 Ullman, B., 144 Untch, K. G., 225 Usami, K., 257 Usher, D. A., 142 Uziel, M., 163 Uznanski, B., 92, 93, 114, 227, 231
Vaetdinov, R. K., 71 Vajna de Pava, O., 180 Vakratsas, Th., 3, 66 Valentine, K. M., 143 Valetdenov. R. K.. 9 Valitova, L: A., 39, 80 Vallee, B. L., 144 Van Boom, J. H., 149, 158 Van de Grampel, J. C., 202, 210
Van de Griend, L. J., 244, 254
van der Gen, A., 173 van der Helm, D., 77, 244, 260
van der Kelen, G. P., 71,250 van der Plas, H. C., 125 van de Sande, J. H., 163 van Deursen, P., 149, 158 van Dijk, J. M. F., 220, 234, 249
Van Dyke, K., 269 Vanier, N. R., 267 van Leusen, A. M., 168 van Swieten, A. P., 124 van Wazer, J. R., 1, 30, 55, 58, 189, 229, 235, 261
Van Zee, R. J., 212 Vargas, L. A., 103, 138 Vasilenko, 0. Ya., 256 Vasil’ev, V. V., 39 Vasudeva-Murthy, _ . A. R.. 205
Vasyanina, M. A., 53 Vaultier. M.. 80 Vedejs, E., 169 Veillard, A., 59 Vela, F., 166 Venetianer, P., 162 Vercellotti, S. V., 131 Vereshchagin, A. N., 252, 263
Verhelst. A.. 24. 54 Verkade; J. G., 244,254,259, 260, 261
Vermeer, H., 256 Vermeer. P.. 9 Vessev. D. A.. 136 Vicic,-J. C., 209 Viets, Yu. A., 56 Vigalok, I. V., 47, 109 Vjjay, I. K., 136 Viktorov. A. V.. 228 Vilesov, F. I., 76 Vincent, J. S., 219, 247 Vineyard, B. D., 7 Vinogradov, L. I., 83 Vinogradova, V. S., 39, 83, ~
245
Vinokurova, G. M., 257 Visscher, M. O., 210 Viswamitra, M. A., 261
Author Index
284 Vivarelli, P., 234 Vizel, A. O., 127, 251 Vlattas, I., 180 Voelker, G., 269 Volkova, V. I., 228 Vol’dman, G. M., 76 Voll, U., 260 Volz, P., 197, 198 Voncken, W. G., 39 von Sonntag, C., 165 Vorkunova, E. I., 265 Voswijlc, C., 202 Vovna, V. I., 76 Vulfson, S. G., 263, 264 Vysotskii, V. I., 86,112 Wada, A., 153 Waerstad, K. R., 210 Wagenknecht, J. H., 224 Wagner, K. G., 150 Wagner, P. D., 157 Wahren, M., 116 Wakabayashi, N., 10 Walaszek, E. J., 228 Walatka, V., 224 Walker, B. J., 4, 69, 101 Walker, G. C., 161 Walker, W. H., 133 Walmsley, F., 266 Wander, J. D., 230 Ward, R. L., 143 Warner, A. H., 155 Warning, K., 10, 11, 65, 192 Warren, C. D., 136, 137 Warren, S., 72, 259 Washecheck, D. M., 77, 244 Wasserman, H. H., 223 Wasserstein, P., 120 Waterman, K., 161 Waters, R. M., 10 Watts, P., 130 Wayland, B. B., 250 Wazeer, M. I. M., 32, 203, 24 1 Webb, S. B., 46, 222 Weber, D., 77, 257 Weber, R., 87 Wedgwood, J. F., 136, 137 Wee, V., 228 Weekes, J. E., 244 Weidlein, J., 251 Weiland, J., 226 Weiner, L. M., 228 Weinkauff, D. J., 7 Weiss. J.. 210. 261
Whitesides, G. M., 30, 33, 59, 236, 238 Whittle, P. J., 35, 237 Wicken. A. J.. 137 Wieber,’ M., 59, 261 Wiechelman. J.. 228 Wife, R. L.,‘l83 Wiffen. J. T., 219, 248 Willhalm, B., 182 Williams, E. B., jun., 140 Williams, F., 220, 247, 248 Williams. G.. 265 Williams; J. C., 230 Williams, J. K., 235, 251 Williams, J. R., 12 Williams, M. E., 63 Williams, R. J. P., 139, 157, 236 Willson, M., 35 Wilson, G. S., 140 Wilson, H R., 261 Wilson, 1. B., 141 Wilson, J. D., 224 Wilson, N. H., 25, 174, 21 8 Wilson, R. D., 209 Wineback, D., 8 Wing, R. M., 113, 260 Winkelman, H., 8 Wirtz, K. W. A., 138 Wiseman, J., 191, 215 Witkop, B., 163 Witkowski, J. T., 148 Wittke, E., 193 Woenckhaus, C., 131 Wolf, R., 29, 35, 41, 42, 44, 206, 236, 261 Wolff, J., 156 Wolfrom. M. L.. 190 97, 199, Wolfsberger, 200, 231 Wolinsky, L. E., 182 Wolkoff, P., 10 Wong, D. Y., 8 5 , 225 Wone. J. Y.. 166 Wong; T. C.’, 28, 262 Wood, D. J., 228 Woods, M., 125, 205 Wrbblewski, A., 186 Wu, A., 184 Wu, R., 161 Wunderlich, H., 59, 261 Wunsch, G., 188, 201, 206, 209 Wunsche, C., 265 Wurmb, R., 209 Wustner, D. A., 113, 260
w.,
Xavier, A. V., 236 Wermuth, B., 152 Werstiuk, E. S., 161 Westhead, E. W., 157 Westheimer, F. H., 120, 158, 191, 215 Westmore, J. B., 57 Wetzel, R. B., 67, 236 Wharton, D. C., 250 White, D. C., 138 White, D. W., 254 Whitehead, M. A., 196, 250 Whitehouse, R., 165, 223
Yakovenko, E. V., 71 Yakovleva, 0. P., 106 Yzkshin, V. V., 88, 252, 254, 268 Yakutina, 0. A., 255 Yamada, A., 165 Yamada, F., 208 Yamada, M., 181 Yamada, S., 124, 174 Yamaguchi, M., 182 Yamaguchi, R., 125 Yamamoto, K., 2, 45
Yzmamoto, S., 141 Yamashita, M., 92 Yamauchi, K., 116, 148 Yamazaki, H., 150 Yamazaki, M., 103 Yanagisawa, A., 257 Yanchuk, N. I., 114,254 Yang, I. Y., 133 Yano, J., 151, 152 Yano, Y., 166 Yaremko, A. M., 252 Yarmukhametova D. Kh., 78 Yastrebovz, G. E., 256 Yasui, T., 208 Yates, J. A., 182 Yathindra, N., 228 Yatsimirskii, K. B., 236 Yee, K. C., 101, 234 Yip, K. F., 150, 162 Yin, P. K. L., 255 Yoneda, S., 85, 226 Yong, K. S., 230 Yoshida, H., 110, 175, 240 Yoshida, T., 144 Yoshida, Z., 85, 226 Yoshifuji, M., 87, 88, 217 Young, D. W., 261 Young, J. C., 135 Yount, R. G., 157 Yuksekisik, N., 128 Yuldasheva, L. S., 92, 108, 126 Yu Mal’kevich, L., 225 Yura, Y., 22 Yurchenko, R. I., 198, 201 233, 250 Yurchenko, V. G., 201, 253, 256 Yurzhenko, T. I., 194 Yushko, E. G., 184 Zaidi, S. M. H., 181 Zaitsev, A. A., 119, 267 Zakharov, V. A., 268 Zakharov, V. I., 62 Zakim, D., 136 Zalik, S., 154 Zamecnik, C., 163 Zamojski, A., 13, 14, 89 Zapuskalova, S. F., 209 ZariDov. N. M.. 262 Zaripovl S. I., 9 Zarytova, V. F., 158 Zasorin, V. A., 198, 199, 268 Zatorski. A.. 183 Zavalishina,‘A. I., 106 Zaychikov, E. F., 154 Zbiral, E., 21, 23, 72, 177 Zeidler, A., 209 Zeil, W., 263 Zelikman, A. N., 76 Zeltmann, A. H., 236 Zenin, S. V., 228, 235 Zeiba, E. N., 120 Zerner, R., 144 Zervas, L., 139 Zhadanov. B. V.. 267 Zhmurova, I. N:, 192, 198, 201, 256:, 268 Zhmurova, N.. N., 233 Zhuravleva. L. P.. 267 Zharba, V.’F., 117 ~
Author Index Ziehn, K.-D., 10, 11, 65 Zielinski, W. S., 158 Ziemnicka, B., 118 Zimin, M. G., 76, 83, 130, 254
Zimmer, H., 184 Zimmerman, G., 116 Zimmerman, S., 261
285 Zimmermann, D., 230 Zingaro, R. A., 15 Zinkovskii, A. F., 81 Zmudska, B., 162 Zolotareva, L. A., 201, 256 Zschunke, A., 5, 8 Zuckerman, J. J., 259 Zumbulyadis, N., 229
Zverev, V. V., 264 Zwierzak, A., 105, 117, 124 Zyablikova, T. A., 41, 83, 127
Zyk, N. V., 84 Zykova, T. V., 45, 50,52,53,
63, 70, 94, 97, 109, 111, 231, 268
