Organophosphorus Chemistry

A Specialist Periodical Report

Organophosphorus Chemistry Volume 2

A Review of the Literature Published between July 1969 and June 1970

SenioGReporter

S. Trippett, Department of Chemistry, The University, Leicester Reporters R. S. Davidson, The University, Leicesfer N. Hamer, Cambridge Universify

D. W. Hutchinson, Universify of Warwick R. Keat, Glasgow Universify

J. A. Miller, Universify of Dundee D. J. H. Smith, The Universify, Leicesfer

J. C. Tebby, Norfh Staffordshire Polytechnic B. J. Walker, Queen’s University of Belfast

SBN : 85186 016 8 @ Copyright 1971

The Chemical Society Burlington House, London, W I V OBN

Orgunic formulae composed by John Wright’s Symbolset method

Printed in Great Britain by John Wright and Sons Ltd. at The Stonebridge Press, Bristol BS4 SNU

Foreword

The comments that we have so far received on the first volume of ‘Organophosphorus Chemistry’ have encouraged us to continue with the same structure in this second volume. The original Reporters were in some cases almost overwhelmed by the volume of work published in their areas and new Reporters have joined us this year. Overlapping has thus become a greater problem; some has been eliminated but much of necessity remains. S. T.

Contents

Chapter 1 Phosphines and Phosphonium Salts By D. J. H. Smith I Phosphines 1 Preparation A From Halogenophosphine and Organometallic Reagent B From Metallated Phosphines C By Reduction D By the Radical Addition of P-H to Olefins 2 Reactions A Nucleophilic Attack on Carbon (i) Activated Olefins (ii) Activated Acetylenes (iii) Carbonyls etc. (iv) Miscellaneous B Nucleophilic Attack on Halogen C Nucleophilic Attack on Other Atoms D Miscellaneous

1

7 7 7 8 11 11 12 14 16

I I Phosphonium Salts 1 Preparation 2 Reactions A Alkaline Hydrolysis B Additions to Vinylphosphonium Salts C Miscellaneous

I II Phosphorins and Phospholes 1 Phosphorins A Preparation B Structure C Reactions 2 Phospholes

18 21 21 25

25

26 26 28 28

28

vi

Contents

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippeff 1 Pseudorotation

29

2 2,2’-Biphenylylenephosphoranes

30

3 1,3,2-Dioxaphospholens

31

4 1,3,2-Dioxaphospholans

34

5 1,3,2-0xazaphospholans

36

6 1,2-0xaphospholens

36

7 Miscellaneous

38

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller 1 Halogenophosphines A Preparation B Reactions (i) NucIeophilic Attack at Phosphorus (ii) Electrophilic Attack at Phosphorus (iii) Miscellaneous

41 41 43 43 45 46

2 Halogenophosphoranes A Structure and Spectra B Reactions

48 48 49

3 Phosphines Containing a P-X Bond (X = Si, Ge, Sn, or Pb) A Preparation B Reactions

52 52 53

Chapter 4 Phosphine Oxides By J. A. Miller 1 Preparation A Using Organometallic or Complex Hydride Reagents B From Alkyl Phosphinites C By Addition Reactions of Secondary Phosphine Oxides (i) To Carbonyl (ii) To other Multiple C=X Bonds D Miscellaneous

55

55 56

57 57 58 59

vii

Contents

2 Reactions Nucleophilic Reactions of P=O and P=S groups Electrophilic Reactions Reactions not involving P=O and P=S Groups Miscellaneous

60 60 61 62 66

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker 1 Introduction

67

2 Phosphorous Acid and its Derivatives A Nucleophilic Reactions (i) Attack on Saturated Carbon (ii) Attack on Unsaturated Carbon (iii) Attack on Oxygen (iv) Attack on Halogen (v) Attack on Hydrogen B Electrophilic Reactions C Rearrangements D Cyclic Esters of Phosphorous Acid E Miscellaneous Reactions

67 67 68 78 85 86 86 88 89 91

3 Phosphonous Acid and its Derivatives

92

4 Phosphinous Acid and its Derivatives

93

67

Chapter 6 Quinquevalent Phosphorus Acids By N. K. Hamer 1 Phosphoric Acid and its Derivatives

A Synthetic Methods B Solvolyses of Phosphoric Acid Derivatives C Reactions

94 94

99 104

2 Phosphonic and Phosphinic Acids and Derivatives A Synthetic Methods B Solvolyses of Phosphonic and Phosphinic Esters C Reactions of Phosphonic and Phosphinic Acid Derivatives

108 108 112

3 Miscellaneous

117

115

...

Contents

Vlll

Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson 1 Mono-, Oligo-, and Poly-nucleotides

A Mononucleotides B Nucleoside Polyphosphates C Oligo- and Poly-nucleotides D Nucleoside Thiophosphates E Physical Methods and Analytical Techniques 2 Coenzymes and Cofactors

A B C D

Phosphoenol Pyruvate Nicotinamide Coenzymes Nucleoside Diphosphate Sugars Other Nucleotide Coenzymes

3 NaturalIy Occurring Phosphonic Acids

A Aminophosphonic Acids B Phosphonomycin

119 119 128 130 134 136 137 137 138 139 142 143 143 144

4 Oxidative Phosphorylation

145

5 Sugar Phosphates A Pentoses B Hexoses

146 146 147

6 Inositol Phosphates and Phospholipids A Inositol Phosphates B Phospholipids

148 148 149

7 Enzymology

150

8 Other Compounds of Biochemical Interest

153

Chapter 8 Ylides and Related Compounds By S. Trippett 1 Methylenephosphoranes A Preparation B Reactions (i) Inorganic Reagents (ii) Halides (iii) Carbonyls (iv) Miscellaneous

156 156 159 159 160 164 170

ix

Contents 2 Phosphoranes of Special Interest

173

3 Selected Applications of the Wittig Olefin Synthesis A Natural Products (i) Prostaglandins (ii) Isoprenoids (iii) Miscellaneous B Carbohydrates C Miscellaneous

175 175 175 175 179 180 181

4 Synthetic Applications of Phosphonate Carbanions

183

5 Ylide Aspects of Iminophosphoranes

187

Chapter 9 Phosphazenes By R. Keat 1 Introduction

191

2 Synthesis of Acyclic Phosphazenes A From Phosphorus Amides B From Carbon Amides C From Sulphur Amides D From Silicon-Nitrogen Compounds E Other Methods

191 191 194 197 198 199

3 Properties of Acyclic Phosphazenes

202 202 205

A Chemical B Physical

4 Synthesis of Cyclic Phosphazenes

206

5 Chemical Properties of Cyclic Phosphazenes A Addition Compounds B Amino-derivatives C Aryl Derivatives D Aryloxy- and Alkoxy-derivatives E Mercapto-derivatives

209 209 209 213 214 21 6

6 Polymeric Phosphazenes

216

7 Miscellaneous Physical Measurements

217

8 Molecular Structures of Phosphazenes and Related Compounds determined by Diffraction Methods

219

Contents

X

Chapter 10 Photochemistry, Radicals, and Deoxygenation Reactions By R. S. Davidson 1 Photochemistry

22 1

2 Radical Reactions

225

3 Deoxygenation of Peroxides and Desulphurisation of Sulphides

228

4 Deoxygenation of Nitro- and Nitroso-compounds

230

5 Miscellaneous Deoxygenation Reactions

233

Chapter 11 Physical Methods By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy A Chemical Shifts and Shielding Effects B Studies of Equilibria and Reactions C Pseudorotation D Restricted Rotation E Non-equivalence and Medium Effects F Inversion and Configuration G Spin-Spin Coupling (9 JPP and JPM (ii) JPF (iii) Jpc (iv) l J p ~and 2 J ~ p ~ (v) JPC,H (vi) JPOGH and JPNGH H Paramagnetic Effects

236 236 240 242 244 245 247 249 250 25 1 252 252 252 257 257

2 Electron Spin Resonance Spectroscopy

260

3 Vibrational Spectroscopy A Band Assignments and Structural Elucidation B Stereochemical Aspects C Studies of Bonding

26 1 26 1 264 265

4 Microwave Spectroscopy and Dipole Moments

266

5 Electronic Spectroscopy

267

6 Rotation

269

7 Diffraction

270

xi

Contents 8 Electrochemical Studies

275

9 Mass Spectrometry

276

10 pK, Reaction Rate, and Therrnochemical Studies

280

11 Surface Properties

28 1

1 Phosphines and Phosphonium Salts BY

D. J. H. SMITH

PART I: Phosphines 1 Preparation A. From Halogenophosphine and Organometallic Reagent.-(4-Bromopheny1)magnesium bromide reacts with chlorodiphenylphosphine below 10 "C to yield diphenyl(4-bromopheny1)phosphine (l).l In a similar

77%

synthesis, tris(3-fluoropheny1)- and tris(4-fluorophenyl)-phosphines have been prepared2 from excess of the corresponding Grignard reagent and phosphorus trichloride. Trimesitylphosphine (2) can be obtained from excess mesitylmagnesium bromide and phosphorus trichloride.a However, when the amount of

\ \2PCl,

a

(2)

-/ 3

G. P. Schiemenz, Org. Synth., 1969, 49, 66. R. De Ketelaere, E. Muylle, W. Wanerman, E. Claeys, and C. P. Van der Kelen, Buff. SOC.chim. belges., 1969, 78, 219. B. I. Stepanov, E. N. Karpova, and A. I. Bokanov, Zhur. obshchei Khim., 1969,39,1544.

2

Organophosphorus Chemistry

Grignard reagent is limited, the product obtained is tetramesityldiphosphine (3). A synthesis of phosphines utilising alkyl transfer from boron to phosphorus has been de~cribed.~ No attempt was made to prevent oxidation to phosphine oxides during work-up and hence chlorodiphenylphosphine and tricyclohexylborane yielded the phosphine oxide (4). Ph2PCl

+ (CeH&B

(C6H&ByPPh2CI

Lithioacetylides and diethyl phosphorochloridite give (5), which can be treated further with Grignard reagent to yield dialkyl-( 1-alkyny1)phosphines (EtO),PCl

+ LiCiCR1

-

1

(EtO),P.CiCR1 (5)

RMgx

R = alkyl R1 = alkyl, aryl

R2P*CiCR1 (6)

The reaction of cyclopropyl-lithium with triphenyl phosphite and chlorodiphenylphosphine gave tricyclopropylphosphine and cyclopropyldiphenylphosphine respectively.6 Tertiary phosphines have been prepared by the treatment of alkyl halides with phosphites, phosphinites, or phosphonites in the presence of sodium, e.g. : Pr'C1

+ (PhO)3P

Pr',P

B. From Metallated Phosphines.-The cis-diphosphine (7) has been obtained * from lithium diphenylphosphide and cis-l,2-dichloroethane. PhzPLi

+ ClCH :CHCl cis

THF .___j

Ph2P CH :CH PPhz cis (7) 30%

P. M. Draper, T. H. Chan, and D. N. Harpp, Tetrahedron Letters, 1970, 1687. A. M. Aguiar, J. R. S. Irelan, C. J. Morrow, J. P. John, and G. W. Prejean, J. Org. Chem., 1969,34,2684. A. H. Cowley and J. L. Mills, J. Amer. Chem. Soc., 1969, 91, 2915. I. Hechenbleikner and E. J. Lanpher, U.S.P. 3,470,254. J. P. Mitchener and A. M. Aguiar, Org. Prep. Proced., 1969, 1, 259.

Phosphines and Phosphonium Salts

3

- -

Issleib has shown that alkyl-substituted diphosphines can be prepared by exchange reactions with tetraphenyldiphosphine: Ph,P.PPh,

+ LiPR,

Ph2P.PR2

R,P-PR,

R = alkyl

The base-catalysed addition of secondary phosphines to vinylphosphines and ethynylphosphines has been described.1° The reaction is useful for the preparation of poly(tertiary phosphines) with CH2CH, bridges between phosphorus atoms : PhPH,

-

+ 2PhzP. CH :CH2

KOBut

9

PhP(CHzCHzPPhJ2 90%

An acyl-substituted phosphine has been prepared by the reaction of sodium diphenylphosphide with acetyl chloride.ll Treatment of lithium diethylphosphide with boron trichloride gave the dimer (8),12 but with excess silicon halide1, products of the type (9) were BCI,

+ LiPEt,

-

R,-,Si(PEt,), (9)

[B(PEt,),], (8)

x=l,3 R = Me, H, C1

-

obtained. Similar products may be obtained from lithium diethylphosphide and (methylsily1)diethylphosphine(10).14 Methylsilylphosphines have been (MeSiH,)PEt, (10)

+ LiPEt,

MeSi(PEt,),

prepared from potassium silylphosphides and methyl bromide.16 Alternatively, (methylsily1)phosphine can be made from silyl bromide and (1 1). The reaction of trisodium phosphide with trichlorophenylgermane or

Li A1H (PH Me) (1 1)

10

11

l2 l3 l4 l6

K. Issleib and F. Krech, J. prakt. Chem., 1969, 311, 463. R. B. King and P. N. Kapoor, J . Amer. Chem. SOC.,1969,91,5191. R. G. Kostyanouskii and V. V. Yakshin, Izvest. Akad. Nauk. S.S.S.R., Ser. khirn., 1969,478. G. Fritz and F. Pfannerer, Z . anorg. Chem., 1970, 373, 30. G . Fritz, G . Becker, and D. Kummer, Z . anorg. Chem., 1970, 372, 171. G. Fritz and G. Becker, 2. anorg. Chem., 1970, 372, 180. K . D. Crosbie, C. Glidewell, and F. M. Sheldrick, J. Chem. SOC.( A ) , 1969, 1861.

4

Organophosphorus Chemistry

trichlorophenylsilane yields heptamers,ls whereas reaction with dipotassium phenylphosphide l7 gave the tetramers (1 2). 7PhMC13

+ 7Na,P

_CC__J

(PhMP),

+ 21NaCl Ph I

4RMC13

+

6K,PPh ---+

12KC1

+

M = Si, Ge Ph

Ph

aluminium hydride reduction of ( +)-benzylmethylphenylpropylphosphonium bromide proceeds with racemisation,ls whereas the corresponding arsonium compound gave the arsine with retention of configuration. A convenient synthesis of methylphosphines l9 involves the reduction of dimethyl methylphosphonite with lithium aluminium hydride. The resulting methylphosphine can be converted into di- or tri-methylphosphine with methyl iodide in methanol, depending upon the conditions used.

C. By Reduction.-Lithium

MeP( :O)(OMe),

+ LiAlH,

-

MePH,

Me1 MeOH >

Me,PH-

Me,P

Reduction of the bisphosphonium salts (13a) with sodium hydride 2o results in the cleavage of the bridge, irrespective of the substituents on phosphorus. It is suggested that the reaction proceeds with initial attack of hydride ion at phosphorus to give a phosphorane which subsequently decomposes. However, when lithium aluminium hydride is used the loss of the bridge is competitive with loss of the benzyl group. H-

-

+ + R3P.CHz-CH,*PR3 3.

(1 3 4

HPR3.CH,.CH,-$R3

The same phosphonium salts can also be reduced very efficiently with cyanide ion.,' Ethylenebis(tripheny1phosphonium) bromide was reduced l7 l8 lS 2o

H. Schumann and H. Benda, J. Organometallic Chem., 1970,21, P12. H.Schumann and H. Benda, Angew. Chern. Internat. Edn., 1969,8, 989. L. Horner and M. Ernst, Chem. Ber., 1970,103,318. K.D.Crosbie and G. M. Sheldrick, J . Inorg. Nuclear Chem., 1969,31, 3684. J. J. Brophy and M. J. Gallagher, Austral. J . Chem., 1969,22, 1399. J. J. Brophy and M. J. Gallagher, Austral. J. Chem., 1969,22, 1405.

Phosphines and Phosphonium Salts

5

with 2 moles of potassium cyanide in DMSO to triphenylphosphine and succinonitrile. One mole of cyanide gave the p-cyanoethyl salt (13),

+

+

Ph,P*CH2*CH,*PPh,

Ph3P + NC*CH:CH2

CN____+

CN-

Ph3P

+ + CH:CH*PPh, + HCN

J

+

NC.CH2*CH2*PPhs

.L

NC * CH2 CH, CN indicating that an elimination-addition sequence is the probable reaction pathway. In a studyz2of the mechanism of reduction of phosphine oxides with trichlorosilane Mislow has shown that the stereochemical course of the reduction of benzylmethylphenylphosphine oxide depends upon the base used. Weak bases (pKb > 7) give predominant retention, whereas strong bases (pKb < 5 ) give predominant inversion. Complex formation does not appear to be important, but reduction with inversion proceeds via a product of the base decomposition of the chlorosilane, whether a derived perchloropolysilane or a trlchlorosilyl anion as shown. This work naturally led to the use of hexachlorodisilane for the reduction of acyclic HSiCI,

+

Et3N

-

SiCl;

+

t

Et3NH

phosphine oxides with inversion of c~nfiguration.~~ In contrast, the reduction of phosphetan oxides (14) with hexachlorodisilane proceeds with retention. These reductions are faster than their acyclic analogues and it aa aa

K. Naumann, G. Zon, and K . Mislow, J. Amer. Chem. SOC.,1969, 91, 7012. K. E. DeBruin, G. Zon, K. Naumann, and K. Mislow, J . Amer. Chem. SOC.,1969,91, 7027.

6

Organophosphorus Chemistry

is suggested that the reaction proceeds with nucleophilic attack at phosphorus.

CI,SiO/ 'Ph

CI,Si

/L

'Ph.

However, the desulphurisation of acyclic phosphine sulphides proceeds with retention,24 presumably via attack of the trichlorosilyl anion on the sulphur atom of the intermediate trichlorosilylmercaptophosphonium ion (15). R..

R1--'P=S /

+

Si2Cl,

R,..+ R1-P-S--SiCI,

R2

R2

/

+

SiCI,

(15)

Rl-P: RJ

+

SiC1,-S-SiCl,

Decyldichlorophosphine (16) can be reduced catalytically with hydrogen over palladium in the presence of triethylamine.26

D. By the Radical Addition of P-H to 0lefins.-Dimethyl- and bis(trifluoromethyl)-phosphines yield tertiary phosphines, e.g. (17) and (18), with olefins 26 and trifluoroethylene on U.V. irradiation. Photolysis of MeCH:CHMe

+ (CF,),PH

hU

(CF,),P-CHMeEt

(1 7)

G. Zon, K. E. DeBruin, K. Naumann, and K. Mislow, J . Amer. Chem. SOC.,1969,91, 7023. zs R. E. Hall, A. Kessler, and A. R. McLain, U.S.P., 3,459,808. R. Fields, R. N. Haszeldine, and J. Kirman, J . Chem. SOC.(C), 1970, 197. *' R. Fields, R. N. Haszeldine, and N. F. Wood, J . Chem. SOC.(C), 1970, 744. 24

-

Phosphines and Phosphonium Salts CHF:CF,

+ Me,PH

7 Me,P.CF,*CH,F

+

Me,P.CHF.CHF, (1 8)

ethereal solutions of alkylphosphines with divinyl ether 28 leads to perhydro-ly4-oxaphosphorins (19). R-PH,

4-

CH2=C,H O

CH,=dH

n

hv

Tzz--+R - P Q

R = alkyl

(19)

Phosphine and divinyl ether in the presence of AIBN gave (19; R = H), which could be converted to (19; R = CaH,,) by photolysis in oct-l-ene. The bridged phosphine (20) can be converted to the highly condensed system (21) by photolysis through in contrast to the oxide (see Chapter 10, Section 1). Tricyclic phosphines have also been made30 by irradiation of cyclododeca-ly5,9-triene with a 6oCosource in the presence of phosphine. Treatment of the resulting product with AIBN in hexane gave a mixture of phosphines.

ZJ* (20)

(21) 25%

2 Reactions A. Nucleophilic Attack on Carbon.-(i) Activated Olefins. The reaction of diethylphosphine with a-chloroacrylonitrile at room tenperature and some 8-substituted acrylonitriles in the presence of triethylamine s1 led to diethylphosphinoacrylonitrile (22). In the absence of triethylamine at - 15 "C,a-chloroacrylonitrile gave the phosphine (23). Et,PH

+ XCH:CHCN

Et3N

> Et,P*CH: CH CN (22)

X = C1, SCH2C6H5 Et,PH 28

+ CH,:CCI.CN

-15 OC

Et,P+CH,CHCl.CN (23)

P. Tavs, Angew. Chem. Internat. Edn., 1969, 8, 751. T. J. Katz, J. C.Carnahan, G. M. Clarke, and N. Acton, J . Amer. Chem. Suc., 1970, 92, 734.

*O

R. F. Mason, U.S.P. 3,435,076. K. D. Gundermann and A. Gaming, Chem. Ber.,

1969, 102,3023,

8

Organophosphorus Chemistry

Chlorodiethylphosphine and acrylonitrile gave a 1 : I-adduct which, it is claimed, might have the structure of an epiphosphonium salt (24). Tris(hydroxymethy1)phosphine and acrylonitrile gave the phosphine (25).

+

Et,PCl

CH,: CHCN

CH-CH-CN

\+/

Et

(HOCH,),P

+ CH, :CH-CN

2,

-

CI -

Et

(24)

(NC CH, CH,),P (25)

Addition reactions of fumaric acids and esters with acrylic compounds are catalysed by tricycl~hexylphosphine.~~

1

R02C*CH:CH-COzR

X = CN, C02H, C0,Me

CH2:CX

I

CHC0,R

I

CH2C02R

-

The vinyl phosphonium salt (26) has been isolated from the reaction of trip henylphosphine with trans-/3-bromovinylphenylsulphone.34

-

PhSO, CH :CHBr

+ Ph,P

+

Br CH :CH PPh, -S02Ph (26)

For the reaction of diphenylcyclopropenones with triphenylphosphine see Chapter 8, Section 1A. (ii) Activated Acetylenes. Phosphines and diacylacetylenes have been shown to give 1,2-alkylidenediphosphoranes (27) which are thermally less stable and more reactive than the corresponding phosphoranes

Ph3P

+

Ph,p\

,c-c

Ph(O:)C.CiC.C(:O)Ph

RG

32

8a

36

0 ,CR \

PPh,

R. K. Valetdinov, E. V. Kuznetsov, and S. L. Komissarova, Zhur. obshchei Khim., 1969, 39, 1744. K. Morita and T. Kobayashi, Bull. Chem. SOC.Japan, 1969, 42, 2732. E. G. Kataev and F. R. Tantasheva, Zhur. obshchei Khim., 1969,39,213. M. A. Shaw and J. C. Tebby, J. Chem. SOC.(C), 1970, 5.

Phosphines and Phosphonium Salts

9

stabilised by ester groups. In the same paper an alternative synthesis of the diphosphorane (28) starting from a secondary phosphine was described. This synthesis could not be used to prepare the acyl diphosphoranes (27)

Me

,C0,Me

I

NaHCO,

PhZI’f

CH-CH

\+

MeO,C/

P PI13

21-

I

Me

since the phosphine adds preferentially to the carbonyl group rather than to the acetylenic bond. Bis(dipheny1phosphino)methane (29) with one equivalent of dimethyl acetylenedicarboxylate 36 gave 5H-diphosph(v)ole (30). In contrast to Ph ,P- CH, -P P h

2

3Me 0-

1,2-a1kylidenediphosphoranesone obtains a P=C-P=C conjugation. Variable temperature n.m.r. indicated the presence of two conformers resulting from restricted rotation about one ester group. Spectroscopic evidence indicated that the buff-coloured, unstable solid from the reaction of cis-l,2-bis(diphenylphosphino)ethylene and dimethyl 36

M. A. Shaw, J. C. Tebby, R. S . Ward, and D. H. Williams, J. Chern. Soc. (C), 1970, 504.

10

Organophosphorus Chemistry

acetylenedicarboxylate was the 1,4-diphosph(v)orin (3 l), but the bis-ylide (32) obtained from 1,2-bis(diphenylphosphino)ethane and the same acetylene 37 hydrolyses only slowly in water. Ph2

CO,Me

I/pph2+

I

c (31)

C0,Me

PhZ Ph, P -CH,.CH,-PPh,

+

(:I;::

Me0,C.C E C * C0,Me ---+

PhZ (32)

The structure of the yellow adduct obtained from 1,2,5-triphenylphosphole and dimethyl acetylenedicarboxylate has been shown3* to be the phosphorane (33), and not that previously reported, which rearranges to the cyclic phosphine (34)in refluxing chloroform.

Ph

x

Yh

X = C0,Me

(33)

(34)

Dideuteriated olefins (35) can be prepared from triphenylphosphine and activated acetylenes in the presence of deuterium Ph3P

+

RCiCR'

+

D20

THF

+

Ph,P\ ,C=C,

R Ph3P0

+

D,

/

R1

l ,R1

c=c\

R'

D

(35)

Sodium diphenylphosphide and 1-bromobut-2-yne in liquid ammonia gave 40 (but-2-yny1)diphenylphosphine (36). However, the reaction with

39

A. N. Hughes and S. W. S. Jafry, J . Heterocyclic Chem., 1969, 6, 991. N. E. Waite and J. C. Tebby, J . Chem. SOC.(C), 1970, 386. E. M. Richards, J. C. Tebby, R. S. Ward, and D. H. Williams, J . Chem. Soc. ( C ) ,

4

W. Hewertson and 1. C. Taylor, Chem. Cumm., 1970, 119.

a7

38

1969, 1542. O

Phosphines and Phosphonium Salts

+ BrCH, - C i CMe

Ph,? Ph,P

+ BrCH,.CiCH

11

---+

-

Ph,P. CH2.C i CMe (36)

1

+ CH,-CiCH

Ph2PBr NH,

Ph,PNH,

3-bromoprop- 1-yne yielded propyne and diphenylphosphinoamine with no product from attack on carbon being observed. The corresponding chlorides react by nucleophilic attack on carbon. (iii) Carbony Is, etc. Triphenylphosphine and NN’-di benzoyl-o-benzoquinonedi-imide in benzene 41 gave the benzimidazole (37) which is thought to have arisen as shown. i0

0

I/

... 1 I-I

+

N -C -PI1

Ph,P -

N- C- Ph I/ 0

COPh

I

O;>-Ph

N=C-Ph LJ I+

OPPh,

-

COPh

I

3hp;*N 3Jc

,Ph

(37)

Diethylphosphine reacted with carbon disulphide 42 in the presence of base to yield the diethylphosphoniobisdithioformate (39) whereas the reaction with diphenylphosphine stopped at the phosphinodithioformate (38) stage. RzPH

-

L

(38) R

=

Ph

(39) R

= Et

(iu) Miscellaneous. a-Halogenobenzyl phenyl ketones and triphenylphosphine 43 afford the ketophosphonium halide (40) and/or the enol41 82

43

M. Sprecher and D. Levy, Tetrahedron Letters, 1969, 4957. 0.Dahl, N. C. Gelting, and 0. Larsen, Acta Chem. Scund., 1969, 23, 3369. I. J. Borowitz, P. E. Rusek, and R. Virkhaus, J . Org. Chem., 1969,34, 1595.

12 X

I

Ph-CO-CHPh + Ph3P

-

Organophosphorus Chemistry

+

O-PPh3 X-

I

Ph.CO*CHPh + PhCZCHPh

I

+PPh3XX = Br or C1 (42) X = OS0,Me

(40)

phosphonium salt (41) depending upon the reaction conditions. If a-mesyloxybenzylphenylketone (42)is used, only the ketophosphonium salt is obtained. The formation of the ketophosphonium salt is best explained by a direct displacement of halide ion by phosphorus, while amechanisminvolving attack on halogen followed by recombination of the resulting ion pair is favoured for formation of the enolphosphonium salt. It has been shown 44 that these reactions are not base-catalysed as previously reported, but that the presence of base simply prevents the acid-catalysed debromination reaction. B. Nucleophilic Attack on Halogen.-The scope of the reaction by which alcohols can be converted into halides with tertiary phosphine and perhalogenocarbon has been extended.46 The reaction shows a remarkable tendency to give inversion products 46 even when solvolysis of the corresponding esters is assisted and gives retention products, e.g. (43).

Tributylphosphine and carbon tetrachloride 47 gave a polymeric waxy solid (44) which could be hydrolysed to tributylphosphine oxide. Bu,P

+ CC14

-10

"C

C37H81C14P3

Hzo

+ Bu3P0

(44)

A relatively stable compound (45) was the product of the reaction of tri(chloromethy1)phosphine and chlorine in carbon tetrachl~ride.~~ (ClCH2)3P

+ C12

CCl4

'

(c13c)2pc13 (45)

I4

*s 47 48

m.p. 192°C

I. J. Borowitz, K. C. Kirby, P. E. Rusek, and E. Lord, J. Org. Chem., 1969,34, 2687. D. Brett, I. M. Downie, J. B. Lee, and M. F. S. Matough, Chem. andlnd., 1969, 1017. R. G. Weiss and E. I. Snyder, J. Org. Chem., 1970, 35, 1627. G. Kamai, R. F. Valetdinov, and E. K. Ismagilov, Zhur. obshchei Khim., 1969,39,379. E. S. Kozlov and S. N. Gaidamaka, Zhur. obshchei Khim., 1969, 39, 933.

Phosphines and Phosphonium Salts

13

Highly chlorinated ketones are dechlorinated by trivalent phosphorus compounds 49 to a,p-unsaturated products (46). 0C(CCl2*CCI,),

+ 2Ph3P

____.*

OC(CC1:CCl,), (46)

-

In a related reaction, dehalogenation of 2,2,3-tribromopropionitrilehas been achieved using triphenylpho~phine.~~ BrCH,*CBr,.CN

+ Ph,P

CH,:CBrCN

+ Ph,PBr,

1,ZDibenzoylethane was the major product from the reaction of triphenylphosphine with the epoxyketone (47).61 This interesting compound

presumably arises from a reaction sequence as shown. The other products from the reaction can be visualised as being produced via an intermediate

-i

+

Ph,P

(47)

+ Ph,P

5%

0-

I

Ph-CO-CH-C-CH,Br I

Ph. CO. CH :CH-CO-Ph

I

I

Ph

+ Ph. CO.CH,Br

1

Ph. CO. CH :PPh, 8%

Phd'

+

Ph. CO.CH,*PPh, Br30%

phosphonium alkoxide formed by initial attack at carbon. phosphite and (47), however, gave the phosphonate (48). 48

s1

K. Pilgram and H. Ohse, J . Org. Chem., 1969, 34, 1592. K. C. Pande and G. Trampe, J . Org. Chem., 1970,35, 1169. A. Padwa and D. Eastman, J . Org. Chem., 1970,35, 1173.

Triethyl

Organophosphorus Chemistry

14 (47)

---+

-I- (EtO),P

‘’‘’c&l’’’ H 0 CH,P(OEt),

li

0

(48)

Borowitz 44 has shown that a-halogenoketones can be dehalogenated with diphenylphosphine. The reaction is not acid-catalysed as is the reaction with triphenylphosphine. A reaction mechanism involving a six-centred transition state has been proposed. Evidence for this includes a Hammett p value of -0.74 and the fact that sterically hindered ketones do not react any slower than unhindered ones.

C. Nucleophilic Attack on Other Atoms.-A Hammett plot of the rates of reaction of triphenylphosphine with ozonides of substituted styrenes 5 2 gave p = +Om72 There was no significant isotope effect in this reaction, which suggests the formation of an unstable phosphorane (49) in the ratedetermining step.

p-0 \

ArHC,

,CH, 0

4- Ph,P

-

Ph, 0-P, I 0 ArHC, 1 CH,

ArCHO

+

HCHO

+

(49)

Ph, P

Dialkyl t-butyl phosphates (50) can be prepared in low yield 53 from the reaction of triphenylphosphine with the corresponding dialkyl t-butyl peroxyphosphates. (RO),P(: 0)* 0 0* But

+ Ph3P

(RO),P( :0) OBut

+ Ph,PO

(50)

Differences in the reactions of tri(o-toly1)phosphine and the meta- and The latter compounds gave phosphine para-isomers have been oxide upon reaction with thionyl chloride, whereas tri(o-toly1)phosphine gave phosphine oxide and sulphide. Tri(o-toly1)phosphine produced the 52 6s 64

J. Carles and S. Fliszar, Canad. J . Chem., 1970, 48, 1309. G . Sosnovsky, E. H. Zaret, and K. D. Schmidt, J , Org. Chem., 1970, 35, 336. S . I. A. El Sheikh, B. C. Smith, and M. E. Sobeir, Angew. Chem. Infernat. Edn., 1970, 9, 308.

Phosphines and Phosphonium Salts

15

compound (5 1) 'stabilised by specific attractions between o-methyl groups and ligands' upon reaction with liquid sulphur dioxide. The other isomers were unreactive. R3P

+ 2SOC1,

-

R,PO

+ S2C1, + (R,PCI,)

R = p-CHS.C,H,,

m-CH,*C,H,

-

R3P0

A complex mixture is obtained from benzotrifuroxan (52) and triphenylphosphine,66containing five compounds whose structures were elucidated by X-ray crystallography.66

Triphenylphosphine reacted with thiodehydrogliotoxin (53) 67 to give the disulphide (54) with retention of configuration at the asymmetric carbon atoms. However, the disulphide gave the monosulphide (55) more slowly and with inversion of configuration of the asymmetric carbon atoms as judged by circular dichroism. Desulphurisation of trisulphides obviously occurs preferentially at the sulphur-bonded sulphur atom.

OH

-

CH,OH (53)

(54)

*.

"

CH2OH

i

slow Ph,P

CH,OH (55)

56

57

A. S. Bailey, J. M. Peach, C. K. Prout, and T. S. Cameron, J, Chem. Soc. (C), 1969, 2277. T. S. Cameron and C. K. Prout, J . Chem. SOC.(C), 1969,2281,2285,2289,2292,2295. S. Safe and A. Taylor, Chem. Comm., 1969, 1466.

16 Organophosphorus Chemistry A 1,3-dipole (56) is thought to be the correct structure for the product

-

from triphenylphosphine and dimethyl azodicarboxylate.s8 Ph,P

+

MeO,C.N:N.CO,Me

+

Ph,P,

,N-G-CO2Me MeOK (56)

A pyrazole (57) was isolated from the reaction of (56) with dimethyl acetylenedicarboxylate.

(‘56)

+ MeO,C*C-C.CO,Me

>-

C0,Me I + N Ph3P-N’ ‘C-C0,Me I II

o=c - c I

I

C0,Me

Me0

C0,Me

C0,Me

I

Ph3P0

+

I

N+CO,M~

M eOL%

0,Me

Me0

Isocyanates and isothiocyanates react in a similar way. Other reactions of the 1,3-dipole are described in Chapter 2, Section 7.

D. Miscellaneous.-It has been shown that allylmethylphenylphosphine does not undergo an allylic ~earrangement.~~ Racemisation, which is slower than racemisation of methylphenylpropylphosphine, must occur via pyramidal inversion. The rate of racemisation of t-butylmethylphenylphosphine 6o is similar to that of the two phosphines above, indicating that steric effects are not significant. Electron-withdrawing substituents in the para-position of the phenyl ring increase the rate of racemisation, indicating that the ( p - p ) ~conjugation affects the barrier to rotation. Similar electronic effects have been observed in a study of the rates of racemisation of diphosphines.61 Hydroxylamine has inadvertently been used as an oxidising agent 6 2 for tertiary phosphines in the preparation of the oximes (58). 58 6@

61

ea

E. Brunn and R. Huisgen, Angew. Chem. Internat. Edn., 1969, 8, 513. R. D. Baechler, W. B. Farnham, and K. Mislow, J. Amer. Chem. SOC.,1969,91, 5686. R. D. Baechler and K. Mislow, J. Amer. Chem. SOC.,1970, 92, 3090. J. B. Lambert, G. F. Jackson, and D. C. Mueller, J . Amer. Chem. SOC.,1970,92, 3093. M. D. Martz and L. D. Quin, J . Org. Chem., 1969, 34, 3195.

17

Phosphines and PhosphoniumlSalts

0

NOH

R

Hydrogenation of unsaturated phosphines (59) was foundto behossible over a palladium catalyst if the nickel(I1) complex was The addition of phosphorus trichloride to dilithiophenylphosphine 64 gave hexaphenyldecaphosphine (60).

Various lithiated tetra-, tri-, and di-phosphines are produced 66 from the addition of phenyl-lithium to ‘phenylphosphorus’ (PhP),. Tertiary phosphines and picric acid give, at room temperature, deeply coloured picrates believed to be covalent in character.s6 At lower temperatures yellow charge-transfer complexes are obtained. An equimolar mixture of triphenylphosphine and NN‘-bisbenzenesulphonyl-p-benzoquinonedi-imide (6 1) has been used as a dehydrating agent in the preparation of anhydrides, amides, and esters.67

0

N SO, P ti

PI1,P 3-

+

N SO,Ph

21iCOZH

-

+

Ph,PO

+

(RC0)20

1 lNSO,Ph

Peptide synthesis employing triphenylphosphine and 2,2’-dipyridyl disulphide in an oxidation-reduction condensation has been described.6s High reactivity with high optical purity is observed, which is rationalised by the intermediate formation of an acyloxyphosphonium salt (62) with predominant pentacovalent character, which reacts rapidly with the aminocomponent. as a* 6K 88

67

L. D. Quin, J. H. Somers, and R. H. Prince, J. Org. Chem., 1969, 34, 3700. M. Van Gheman and E. Wiber, U.S.P. 3,471,568. K. Issleib and F. Krech, Z . anorg. Chem., 1970, 372, 65. M. Beg, A. Arshad, and M. S. Siddiqui, Pakistan J. Sci. Ind. Res., 1969, 12, 19. M. Sprecher and D. Levy, Tetrahedron Letters, 1969, 4563. T. Mukaiyama, R. Matseuda, and M. Susuki, Tetrahedron Letters, 1970, 1901.

1s

Organophosphorus Chemistry

R R1 I I XNHCHCON HCHCOzY

0 II

--+

RCONHRl

+

Ph3P0

+

The chromatography of phosphines using various adsorbents has been reported.6B For the reaction of triphenylphosphine with TCNE and related compounds see Chapter 10, Section 2. PART 11: Phosphonium Salts 1 Preparation The quaternisation of triarylphosphines has been achieved using benzyne intermediate^.'^ The reaction of o-lithiofluoroaromatics with the phosphine at -75 "C leads to a mixture of betaines which can be protonated with fluorene. The same mixture is obtained from the lithiofluoroaromatics(63) and (64). H 3 c 0 ; i

(63)

\

H3C Ar,P

O9

70

+

ofAr3 -m +

CH,

M. C. Gonnet and A. Lamotte, Bull. SOC.chim. France, 1969, 2932. G . Wittig and H. Matzura, Annalen, 1970, 732, 97.

+

C,H, -PAr,

Phosphines and Phosphonium Salts

19

Tetra-arylphosphonium salts have been formed under Ullmann conditions by the reaction of triarylphosphines with iodobenzene in the presence of copper powder and cuprous iodide in DMF as Ph,P

+ PhI

'

~Ph,P ICuI~

~

3.

'

~

44%

Phosphorus pentachloride and phenylacetylene afforded tetrakisqchlorostyry1)phosphonium chloride (65) in low yield in the presence of iodine.' PCl,

+ PhC i CH

trace I z t

(PhCCI :CH),;

C1-

14% The nature of the phosphonium salt formed from the reaction of phosphorus pentachloride with vinylsilanes (66) depends upon the nature of (65)

x.73

PC15 f

+

R3Si.CH:CHX--+ XCH: C(SiR,) .PCI, PCIG

X = OMe, OEt

+

XCH:CH.PCl, PC1,-

X =BuS,PhCH, S

Quaternisation of triphenylphosphine with 1,3,2-dioxathiolan 2,2dioxide 74 gave the phosphonium salt (67).

Aminophosphonium salts (68) are obtained from the quaternisation of phosphines with N-brorn~amines.~~ R,NBr

+ R,P

+

___j

R,N-PR3 Br(68)

The synthesis of phosphonium salts containing the silyl group attached to phosphorus using silylcobalt tetracarbonyls (69) has been d e ~ c r i b e d . ~ ~ 71

73 74 76 76

A. V. Grib, Izuest. Akad. Nauk. S.S.S.R.Ser. khim., 1969, 195. Ya. P. Shaturskii, L. S. Moskalevskaya, G. K. Fedorova, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 213.

N. V. Komarov, V. G. Rozinov, L. P. Vakhrushev, E. F. Grechkin, and N. F. Chernov, Izvest. Akad. Nauk S.S.S.R. Ser. khim., 1969, 729. D. A. Tomalia, U.S.P. 3,471,544. D. F. Clemens, W. Woodford, E. Dellinger, and 2. Tyndall, Inorg. Chem., 1969,8,998. J. F. Bald and A. G. MacDiarmid, J . Organometallic Chem., 1970, 22, C22.

Organophosphorus Chemistry No phosphonium salts are formed if electronegative groups are attached to either phosphorus or silicon. 20

Me,Si.Co(CO),

hexane + + PMe3 roomtemp. Me,Si.PMe,

Co(CO),-

(69)

Tri(cyclopropy1)phosphine and cyclopropyl bromide gave the tetracyclopropylphosphonium salt, which dissociates in solution.e Alkylated 1,4-diphosphoniacyclohexa-2,5-dienesalts (70) have been prepared from dialkyl-1-alkynylphosphines and hydrogen halide in acetic The yield of the/?-halogenovinylphosphine(71) by-product is decreased when hydrogen chloride is used instead of hydrogen bromide, indicating that the reaction mechanism is probably a series of acid-catalysed Michael additions, with halide ion competing with phosphine in the first step.

R2PC-CR1

+

HX

I ' I' I R,PC=CR1

X- --+

" 11R2PCH=CR1

X-

X

R,PC=CR'

R,PCH =CR'X

(71)

R'

-R

(70)

Tautomerism of (70)takes place in refluxing glacial acetic:acid a new organophosphorus heterocycle (72).

78

to give

The condensation of the cyclohexenediol (73) with triphenylphosphonium bromide 70 resulted in dehydration to yield the phosphonium salt (74). 77

?*

79

A. M. Aguiar, J. R. S. Irelan, G. W. Prejean, J. P. John, and G. J. Morrow, J . Org. Chem., 1969,34,2681. A. M. Aguiar, G. W. Prejean, J. R. S. Irelan, and G. J. Morrow, J. Org. Chem., 1969, 34, 4024. J. D. Surmatis, A. Walser, J. Gibas, and R. Thommen, J. Org. Chem., 1970, 35, 1053.

Phosphines and Phosphonium Salts

21

ofHzPP 4-

CH,OH H

O H

O

+

+

Ph,PH Br- --+

(74)

(73)

The preparation of a-chloro-substituted phosphonium salts from alkylidenephosphoranes is described in Chapter 8, Section 1B.

2 Reactions A. Alkaline Hydrolysis.-The alkaline hydrolysis of triphenylvinylphosphonium bromide with N NaOH gave (79, formed from rearrangement of the intermediate phosphorane (76). Another product, 1,Zbis(diphenylphosphiny1)ethane (77), is thought to arise from nucleophilic attack of the diphenylphosphinyl anion on unchanged salt, a scheme which is supported by the detection of styrene in the reaction mixture. Ph

c

Ph3P-CH = CH,

+

Ph -... I L P- CH =CH, *-

Ph

4 Lo

L

I Ph2P*CHPh* CH3

II

f---

0

Ph ,P*CHPhCHzII 0

(75) 1.

Ph,P*CHz*CH2.PPhz4

II

0

II

Ph,PCH=CH,

Ph2P=0

+

PhCH=CH,

0

Epimerisation has been found to proceed faster than hydrolysis in the base-catalysed cleavage of l-benzyl-1-phenyl-2,2,3,4,4-pentamethylphosphetanium bromides (78) (producing a mixture of phosphine oxides *l). In a related studys2 it has been shown that the ylides derived from cis- (78) and trans- (78) can also equilibrate. While pseudorotation undoubtedly occurs in the alkaline hydrolysis, it is difficult to see how ylide interconversion can proceed by such a process.

88

J. R. Shutt and S. Trippett, J. Chem. SOC.(C), 1969,2038. S. E. Cremer, R. J. Chorvat, and B. C. Trivedi, Chem. Comm., 1969, 769. J. Corfield, J. R. Shutt, and S. Trippett, Chem. Comm., 1969, 789.

2

22

Organophosphorus Chemistry Me

& '

(79a): (79b) = 9:l

Ph

"0

The hydrolysis of the optically active 2,2,3,3-tetramethylphosphetanium salt (80) proceeds with retention of configuration, the benzyl anion departing from the equatorial position in (81), or, after one pseudorotation, from the apical position of (82). The apparent anomaly in the hydrolysis of (78) has been explained by steric effects.s3 M eMee Me M e --+ M Me e e Me M e P -CH,Ph +\ Ph.

(80)

P---CH,Ph

HO"Ph (81)

M eMev Me M e P-CH,Ph / 'OH Ph

M Me e e Me M e / Ph

\*

(82)

The cis- and trans- isomers of the salt (83) do not interconvert under conditions where there is complete deuterium exchange.84 More vigorous conditions result in ring opening but there is still no crossover. Presumably pseudorotation is prevented because it would mean putting two t-butyl-like groups in apical positions (84), a high-energy situation.

(Ethoxy)methyl-@-naphthylphenylphosphonium nitrate and the corresponding ethylthio-hexachloroantimonate hydrolyse with inversion at phosphorus, indicating that a pseudorotation process does not occur in either case.24 The inversion of configuration observeds6 in the hydrolysis of t-butyl alkoxyphosphonium salts (85) is in contrast to the retention observed for 83

8G

K. E. DeBruin and K. Mislow, J. Amer. Chem. SOC.,1969, 91, 7393. S. E. Cremer and C. H. Chang, Chem. Comm., 1969, 1456. R. A. Lewis, K. Naumann, K. E. DeBruin, and K. Mislow, Chem. Comm., 1969, 1010.

Phosphines and Phosphonium Salts

23

other t-butyl phosphonium salts.*6 The difference is attributed to the nature of the leaving group, which in the former case is more electronegative than carbon. SbC1,P 11 Ph,+ -OH I --.P-OEt + HO-P-OEt : \ But 1 But Me Me

-OH +.

Ph O=Pc \ But Me

(85)

A careful study83 of the product ratios from the alkaline hydrolyses of the diastereoisomers of ethoxymenthoxymethylphenylphosphonium hexachloroantimonate (86) provides evidence for pseudorotation and leads to the view that there is steric control in product formation. The attack of hydroxide ion opposite menthoxy- is kinetically preferred to attack opposite the ethoxy-group.

SbC1,-

OEt SbC1,-

(88)

The preference of the four-memberedring for the apical-equatorial position is again shown 23 in the hydrolyses of the cis- and trans-ethoxyphosphonium salts (87), which proceed with retention of configuration. The reduction of 3-methyl-1-phenylphospholane-1-oxide(88) with hexachlorodisilane surprisingly proceeded with predominant inversion of config~ration,~~ even though the hydrolysis of the corresponding benzyl salts and reduction with phenylsilane proceeded with retention.88 Apparently when both the nucleophile and the departing anion are highly electronegative, the gain in stability by placing both these groups apical more than compensates for the induced strain when the five-membered ring is placed diequatorial. A kinetic study of the alkaline hydrolysis of ethylene-bis-phosphonium salts (89) has shown that a McEwen-type mechanism is operating.8s With 86

89

S. Trippett in ‘Organophosphorus Chemistry’ (Specialist Periodical Report), ed. S. Trippett, The Chemical Society, 1970, vol. 1, p. 28. W. Egan, G. Ghauviere, K. Mislow, R. T. Clark, and K. L. Marsi, Chem. Cornrn., 1970, 733. K. L. Marsi, J. Amer. Chern. SOC.,1970, 91, 4724. J. J. Brophy and M. J. Gallagher, Austral. J . Chern., 1969, 22, 1385.

Organophosphorus Chemistry

24

benzyl-substituted phosphorus atoms, loss of benzyl is competitive with fragmentation. The nature of the products obtained on hydrolysis of the salts (90) depends upon which reagent is in excess. Fragmentation can again be prevented if one uses a benzyl-substituted phosphorus atom.O0

+

+

+

Ph, P*CH2*CH2*PPh,+HOP(Ph,).CH2-CH2-PPh,

(89) +-~P(Ph,)--CH,

CH,c;Ph,,

W-

-

Ph3P :0

+

CH,: CH,

+

PPh,

0

II

PPh2 excess -OH

-OH _____, excess salt

f-------

(PPh, II

I P+E* Ph,

Ph2

0

(90)

When one isomer of the salt (91) was treated with aqueous base a mixture of oxides was produced. It would be interesting to see if the other isomer did the same and whether the isomeric salts could be interconverted in aqueous base.

The salts (92) have been hydrolysed by base in DMSO.sl When R = H, the P-phenyl bond is broken but when R = Ph, there is predominant cleavage of the cyclopropyl-C-P bond. This has been used as an experimental estimation of the pK,'s of diphenyl- and triphenyl-cyclopropene. PhwPh

-&I H X PPhz

phYph

II 0

R PPh,

ao*(32)

y= Ph3P=0 Ph

+

Ph

Ph Ptl

G . E. Driver and M. J. Gallagher, Chem. Comm., 1970, 150. M.A. Battiste and C. T.Sprouse, Tetrahedron Letters, 1969, 3165.

25

Phosphines and Phosphoniurn Salts

See Chapter 2 for the various topological representations of the stereochemistry of nucleophilic substitution reactions of phosphonium salts that have appeared. B. Additions to Vinylphosphonium Salts.-The use of adducts of vinylphosphonium salts and lY3-dipolesto yield further products by secondary steps has been Diphenyldiazomethane and triphenylvinytphosphonium bromide in methylene chloride gave a quantitative yield of (93). The ylide (94) formed by the action of base, gave a normal Wittig reaction. A high yield of 5,5-diphenyl-3H-pyrazoline(95) was obtained by reaction with sodium hydroxide. The action of heat gave the phosphonium salt (96), in contrast to the pyrolysis of the adduct from diazomethane and triphenylvinylphosphonium bromide, which gave pyrazoline hydrobromide (97) quantitatively.*

+

Ph3P-CH=CH,

4-

Ph3PCH=CH,

+ CH,N,

+

Ph Ph t C \ H , + PhzCNz 4 N\ ,CH-PPh, N

N3+ 3 A

I1

N

PPh,

>

HNz-. I

:+,;

HN'-

For the reaction of triphenylvinylphosphonium bromide with benzoin see Chapter 8, Section 1A. C. Miscellaneous.-In the presence of triethylamine, (prop-2-yny1)triphenylphosphonium bromide and benzoic acid form an adduct (98), presumably via the allenic salt, which can be used for the acylation of amine~.~~ O8

E. E. Schweizer, C. S. King, and R. A. Jones, Chem. Comm.,1970, 39. G. D. Appleyard and C. J. M. Stirling, J. Chem. SOC.(C), 1969, 1904.

* The structures of (93) and the adduct obtained from diazomethane and triphenylvinylphosphonium bromide have been revised (E. E. Schweizer, C. S. Kim, and R. A. Jones, Chem. Comm., 1970, 1584).

26

Organophosphorus Chemistry

+

Ph3P.CH,-CiCH

PhNHeCOR

PhCO H

[Ph,;.CH:CH:CH,]

+

PhNHz

-

Ph3P* CH, C :CH,

I OCOR

3.

+

(98)

Ph,P.CH,-CO.CH,

Allyltriphenylphosphoniumbromide rearranges on basic alumina to the prop- 1-enyl compound 94 which undergoes cathodic cleavageto propene and triphenylphosphine. The same rearrangement takes place thermally.96 In the same study, dehydrohalogenation of the salt (99) with one equivalent of base, or by heating it in diglyme, gave the allenylphosphonium salt (100) which was unreactive with methanol or t-butylthiol but with aniline gave (101). Treatment of (100) with more base yielded the cumulative ylide (102) (see Chapter 8). Et,N

t

>

Ph,P.CH,.CBr:CPhz (99)

+

Ph,P*CH,*C :CPh,

I

+

Ph,P.CH:C:CPha

Ph3P:C: C: CPh,

NHPh (101)

(102)

The 13C and l 8 0 isotope effects in the carbon dioxide formed in the acetolysis of triphenyl(carbobenzhydryloxymethy1)phosphonium bromide support a fragmentation process into benzhydryl carbonium ion, carbon dioxide, and methylenetriphenylphosphorane which is solvent-assisted.ss Other mechanisms operate for other salts when there is no likelihood of a stabilised carbonium ion being formed.

PART III: Phosphorins and Phosphoies 1 Phosphorins A. Preparation.-A new synthesis has been des~ribed.~'The phosphine oxide (103) produced by the dimerisation of the enone (104) with triethyl phosphite could not be reduced directly, but was converted into the dichloride and reduced with phenylsilane. Pyrolysis then gave (105). B4 s6

O6 s7

L. Horner, I. Ertel, H. D. Ruprecht, and 0. Belovsky, Chem. Ber., 1970, 103, 1582. K. W. Ratts and R. D. Partos, J. Amer. Chem. SOC.,1969, 91, 6112. S. Seltzer, A. Tsolis, and D. B. Denney, J. Amer. Chem. SOC.,1969, 91, 4236. G. Markl, D. E. Fischer, and H. Olbrich, Tetrahedron Letters, 1970, 645.

Phosphines and Phosphonium Salts

27

0 R-P,

,CH,OH CH,OH

+

reflux

(PhCH=CH)&=O

pyridiiie

R O FI ’ h R SeO, EtOH/R = PhCH,

CH,Ph Ph

I

Ph

J.

Ph

-A 0

(i) PCl, (ii) PhSiH,

Ph

Ph I CH,Ph

(EtO),P

Ph

Ph 04’\CH,Ph

Ph CH, Ph

(1 05)

A new class of phosphorus compound (106) has been prepared in a synthesis starting from one of the products of the photochemical cycloaddition of l-phenyl-3-phospholene oxide and dichloromaleimide.B8 (See Chapter 10, Section 1.) Azaphosphatriptycene (107) can be synthesised from tris(o-bromopheny1)amine using butyl-lithium followed by triphenyl phosphite.OO The slP spectrum of (107) is at very high field, + 80 ppm (CDCl,), using 35% HsPOl as standard.

gy 99

G. Mark1 and H. Schubert, Tetrahedron Letters, 1970, 1273. D. Hellwinkel and W. Schenk, Angew. Chem. Internat. Edn., 1969, 8, 987.

28 Organophosphorus Chemistry B. Structure.-The crystal structures of 1,l-dimethyl- loo and 1,l -dimethoxy-triphenylphosphorinlol have been determined and show that these compounds, like the phosphorins, owe their unusual stability to the presence of a delocalised aromatic ring.

C. Reactions.-Phosphorins have been oxidised with 2,4,6-triphenylphenoxyl radical to diaryloxyphosphorins (108).lo2In a similar reaction, the diphenylamino-radical gave the diphenylaminophosphorin (109). Both of these compounds can be oxidised, with lead@) benzoate or electrolytically, to the radical cation, in agreement with the presence of an aromatic nucleus. Ph O\ P ArO’

h

t---

phfiph

a

ph

PhZN -NPh,

,

Ph2N’

‘OAr

( 108)

Ar

4 ph

‘NPh,

(109) =

2,4,6-triphenylphenyl

2 Phospholes A review of the synthesis and reactions of phosphole derivatives has appeared.lo5 Quin has publishedlo4 a full account of his studies on l-methylphosphole confirming considerable delocalisation in the ring. A simple preparation of P-phenylphospholes, e.g. (1lo), has been reported lo5which consists of dehydrobromination of the adduct of a conjugated diene and dibromophenylphosphine with DBU in boiling benzene.

(1 10)

Further syntheses of dibenzophospholes (111) by o-hydrogen abstraction of tetraphenylphosphonium compounds with lithium bases are described.loB The low value of 16 kcal mol-1 for the inversion barrier of l-isopropyl-2methyl-5-phenylphosphole(112) has been attributed to ( 3 p - 2 ~ delocalisa)~ tion and aromaticity of the phosphole nucleus.1o7 Ph,P+ Br-

LiNEt,

>o-n ‘

P

’ Ph (111)

M e O F h CH(Me), (1 12)

J. J. Daly and G . Markl, Chem. Comm., 1969, 1057. lol U. Thewatt, Angew. Chem. Internat. Edn., 1969, 8, 769. loa K. Dimroth, A. Hettche, W. Stade, and F. W. Steuber, Angew. Chem. Internat. Edn., loo

1969, 8, 770.

A. N. Hughes and C. Srivanavjt, J. Heterocyclic Chem., 1970, 7 , 1. lo* L. D. Quin, J. G. Bryson, and C. G . Moreland, J . Amer. Chem. SOC.,1969, 91, 3308. lo6 M. F. Mathey, Compt. rend., 1969, 269, C , 1066. loo B. R. Ezzell and L. D. Freedman, J. Org. Chem., 1969,34, 1777. lo’ W. Egan, R. Tang, G. Zon, and K. Mislow, J. Amer. Chem. SOC.,1970,92, 1442. loS

2 Quinquecovalent Phosphorus Compounds BY S. TRIPPETT

1 Pseudorotation Additional topological 1-3 and non-topological representations of the processes of pseudorotation via a Berry mechanism have appeared. The preferred variation of a Balaban6 20-vertex graph is shown in the projections used by Mislow (l), by Cram (2), and by Nasielski (3). Each vertex 14

34

45

35

35

45

34

25

25

34

34

-

23

1'1

(3) a

*

K. E. DeBruin, K. Naumann, G. Zon, and K. Mislow, J . Amer. Chem. SOC.,1969,91, 703 1. D. Gorenstein and F. H. Westheimer, J. Amer. Chem. SOC., 1970, 92, 634. M. Gielen and J. Nasielski, Bull. SOC.chim. belges, 1969, 78,339. M. Gielen, C. Depasse-Delit, and J. Nasielski, Bull. SOC.chim. belges, 1969, 78,357. A. T. Balaban, D. Fgrcagiu, and R. Bani&, Rev. Roumaine Chim., 1966, 11, 1205.

30

Organophosphorus Chemistry

corresponds to one of the twenty possible trigonal bipyramids, designated by the groups occupying apical positions, and enantiorners are shown, for example, by 12 and 12. If a ring, which cannot span the diapical position, is present, (1) simplifies to the very useful (la), the ring being represented by substituents 1 and 2. The principles of pseudorotation are now being widely applied, particularly to phosphoranes postulated as intermediates in substitution processes at phosphorus. To avoid overlap, these are discussed in the subject chapters relating to the compounds being substituted. For n.m.r. investigations of stable quinquecovalent phosphorus compounds see Chapter 11.

2 2,2’-Biphenylylenephosphoranes Pseudorotation does not occur in the (8-dimethylamino-1-naphthy1)phosphorane (4) up to 120 “ C ;all the methyl groups are different including the two on nitrogen, both inversion at nitrogen and rotation around the

88 +

Me

Me

(7) S(31P) -t 82 p.p.m.

31

Quinquecovalent Phosphorus Compounds

naphthyl-nitrogen bond being sterically restricted.6 The activation energy of pseudorotation, AG* = 23.5 kcal mol-l, observed in the corresponding (8-methoxy-1-naphthy1)phosphorane raises the interesting possibility of obtaining these compounds in stable optically active forms. The hexaco-ordinate anion ( 5 ) was obtained as shown with either phosphonium ion or lithium as cation depending on the ratio of reactants. The corresponding anion from 1,s-dihydroxynaphthalene was also prepared. The dilithium salt of catechol with either phosphorus pentachloride or the chlorophosphorane ( 6 ) gave the anion (7), isolated as the bis(2,2'-biphenyly1ene)ammonium salt, which was stable in ethanol and in water. This anion had previously been obtained as the triethylammonium salt from phosphonitrilic chloride trimer and catechol in the presence of triethylamine, but was not positively identified at that time. 3 1,3,2-Dioxaphospholens While the phosphite (8; R1 = OMe) required heating at 100 "C for 30 h with butadienes in order to give the phosphoranes (9), the corresponding phosphonite (8; R1= Ph) reacted exothermically with butadienelO and with isoprene.ll This suggests that attack on the diene is an electrophilic process. Hydrolysis of the phosphoranes (9; R1 = Me or Ph, R2= Me) gave the 3-phospholens (10). @

Me

'

lo

l1

D. Hellwinkel and H. J. Wilfinger, Tetrahedron Letters, 1969, 3423. D. Hellwinkel and H. J. Wilfinger, Chem. Ber., 1970, 103, 1056. H. R. Allcock, J. Amer. Chem. SOC.,1964, 86, 2591. N. A. Razumova, F. V. Bagrov, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 2369. N. A. Razumova, F. V. Bagrov, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 2368. M. Wieber and W. R. HOOS, Tetrahedron Letters, 1969, 4693.

32

Organophosphorus Chemistry

The bromophosphorane (1 1; R1= Br), obtained from (8; R1= Br) and butadiene, with water gave l2 a compound to which the hydroxyphosphorane structure (12; R2= H) was assigned. This compound with diazomethane gave (12; R2 = Me) from which catechol was isolated after hydrolysis. The phosphorane (12; Ra= Me) was a highly crystalline substance, m.p. 112-1 14 "C, whereas the authentic material (9; R1= OMe, R2 = H) had b.p. 100-101 "C/2mm and was 'capable of crystallising on standing'. Hydrolysis of the fluorophosphorane (1 1 ; R1= F) @

OR2

(13)

with water at 70 "C gave the phosphinate (13) from which, after treatment with diazomethane and hydrolysis, catechol monomethyl ether was obtained.12 The different hydrolytic behaviour of the bromo- and fluorophosphoranes was ascribed to the different strengths of the phosphorushalogen bonds.

(15) I*

N. A, Razumova, Zh. L. Evtikhov, A. K. Voznesenskaya, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 176.

33

Quinquecovalent Phosphorus Compounds

1,2-Naphthoquinone and triethyl phosphite gave l 3 the phosphorane (14), identical with that obtained from the phosphite (15) and diethyl peroxide. The products obtained l4 from acyl chlorides and the glyoxal-trimethyl phosphite adduct (16) have now been shown l6 to be the 0-acylated compounds (17). This contrasts with the C-acylation observed with the corresponding biacetyl adduct la (18; R1= Me). However, with the biacetyl adduct (18; R1= Et), attack on the carbon or oxygen depends l7 on the electrophile; with diethyl phosphorochloridite, the product (19) of attack on oxygen was obtained.

omo

3- R - C O - C l

-

R-CO-O*CH:CH-O-P(:O)(OMe), (17)

P ''

(OM43 (16)

-

(19)

Me

-

(EtO),P(: 0) CMe :CMe * 0 P(OEt),

74%

Me

(18)

R1 = Me, E\

R2.CO - CMe(C0 .Me) -0-I?(:

0) (OR1),

a-Chloro-/3-ketosulphides(21) have been obtained l8 from the exothermic reactions of the benzil-trimethyl phosphite adduct (20) with sulphenyl chlorides. These are neither radical nor carbene reactions and an ionic mechanism is suggested.

CY ' S-R -+Ph.CO.CPhCl*SR (21) 50-93%

l3

14,

l6 l6 l7

1*

D. B. Denney and D. H. Jones, J . Amer. Chem. Suc., 1969,91, 5821. F. Ramirez, S. L. Glaser, A. J. Bigler, and J. F. Pilot, J. Amer. Chem. Suc., 1969, 91, 496. F. Ramirez, S. L. Glaser, A. J. Bigler, and J. F. Pilot, J . Amer. Chem. Soc., 1969,91, 5966. F. Ramirez, S. B. Bhatia, A. J. Bigler, and C. P. Smith, J. Org. Chem., 1968, 33, 1192. I. P. Gozman, Zhur. ubshchei Khim., 1969, 39, 1954. D. N. Harpp and P. Mathiaparanam Tetrahedron Letters. 1970, 2089.

OrganophosphorusChemistry

34

For the photolytic reactions of the biacetyl-trimethyl phosphite adduct with ketones see Chapter 10. 4 1,3,2-Dioxaphospholans 1 :2-Adducts have been obtained from phosphonites and butyl glyoxalate lS and from phosphites and diethyl mesoxalate lS and (-)-menthy1 pyruvate.20 The adduct of the last with trimethyl phosphite gave (-)-2,3dimethyltartaric acid on hydrolysis; this was rationalised in terms of minimisation of non-bonded repulsions in the transition state for formation of the adduct. The phosphoranes (22), from ethyl ethylene phosphites and diethyl peroxide, decompose at or above room temperature l3 to give epoxides and triethyl phosphate. The formation of the cis-epoxide (24) from the transphosphorane (23) supports a mechanism involving a betaine intermediate.

Me :l>P(OEt) Me

[Fl:;+ Me

.__f 117°C

P(OEt),

Me

(EtO),PO

yo\+

Me €4'- MeP(OEt)3 -0 ' H

(23) Me

I

"b

Me

H

(24)

The observed relative rates of reaction of phosphites with diethyl peroxide (ethyl o-phenylene faster than saturated five-membered faster than acyclic and six-membered) suggest l3 that the phosphoranes are formed directly and not via intermediate phosphonium ethoxides. The increased ring-strain on going to tetrahedral intermediates would lead to the opposite order. The condensation of a-glycols with tris(dimethylamino)phosphine, to give phosphoramidites (25) or tetraoxyspirophosphoranes (26) depending on the ratio of reactants, has been extended 21 to a wide range of a-glycols including chiral molecules which give rise to interesting diastereoisomers. lo

A. N. Pudovik, I. V. Gur'yanova, and S. P. Perevezentseva, Zhur. obshcheiKhim., 1969, 39, 1532.

2o

21

M. Muroi, Y. Inouye, and M. Ohno, Bull. Chem. SOC.Japan, 1969,42,2948. H. Germa, M. Sanchez, R. Burgada, and R. Wolf, Bull. SOC.chim. France, 1970, 612.

Quinquecovalent Phosphorus Compounds

35

The spirophosphoranes (26) are stabilised 22 by methyl substituents; pinacol will displace either one or both of the ethylene glycol residues of (27) depending on the ratio of reactants. A 1 : 2 ratio of (27) and pinacol gave entirely the phosphorane (28). This phosphorane on heating with alcohols gave the phosphonate (29) instead of the expected phosphite, cf. (30) from (27).

-N Me,

R -f> :P

'y

(25)

+ PWMe,),

Y

H (26)

+ HO-CH2*CH2*OH

R O ) : [ (30)

H

H

+

2a

[;;P-o.co.R

H

-

H. Germa, M. Willson, and R. Burgada, Compt. rend., 1970, 270, C , 1426, 1474.

Organophosphorus Chemistry The trifluoroacetyl phosphite (3 1 ; R = CF,) reacted 23 twice as rapidly with butadiene as did the acetyl phosphite (31; R = Me), coniirming the increased reactivity of PI1[compounds with dienes with increasing electronacceptor ability of the substituents on phosphorus. 36

5 1,3,2-Oxazaphospholans Spirophosphoranes (32), (33), and (34) have been prepared as shown 24, 25 from a wide variety of 2-aminoalcohols, including (+) and (-)-ephedrine and L-alaninol, and the various stereochemical possibilities demonstrated by n.m.r. spectros~opy.~~, 26

+ P(NMe,),

+ R1

NHR2

6 1,2-Oxaphospholens Among new @-unsaturated ketones (35) used in the formation of 1 : l-adducts with tervalent phosphorus compounds (36) are methyl vinyl a3

ar *@

Zh. L. Evtikhov, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1969,39, 2367. M. Sanchez, L. Beslier, and R. Wolf, Bull. SOC.chim. France, 1969, 2778. J. Ferekh, J.-F. Brazier, A. Munoz, and R. Wolf, Compt. rend., 1970, 270, C, 865. M. Sanchez, L. Beslier, J. Roussel, and R. Wolf, Bull. SOC.chim. France, 1969, 3053.

37

Quinquecovalent Phosphorus Compounds

ketone,,* 27 ethyl benzylideneacetoacetate,2* 28 ethyl isopropylideneacetoacetate, isopropylideneacetylaceton e, and methyleneacetylacetone. Those with R6 = Rsare particularly useful as this reduces the number of isomers in the products. For a description of the n.m.r. spectra of these adducts see Chapter 11. (R10),PR2t3-,,)

+

R3* CO * CR4:CR'R'

Additional evidence has been presented2Bs30for the structures of the phosphoranes (38) and (39) obtained31 from the phenolic Mannich base (37) and tris(diethy1amino)phosphine.

+ P(NEt2), CH,.NEt,

(37)

+

+ kEt,

Me

(39) p7

A. K. Voznesenskaya, N. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 1033.

ao

81

B. A. Arbusov, E. N. Dianova, and V. S. Vinogradova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1109. B. E. Ivanov, A. B. Ageeva, S . V. Pasmantuk, and R. R. Shagidullin, Izuest. Akad. Nauk S.S.S.R.,Ser. khim., 1969, 154. B. E. Ivanov, A. B. Ageeva, S . V. Pasmantuk, R. R. Shagidullin, S . G. Salikhov, and E. I. Loginova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1757. B. E. Ivanov, A. B. Ageeva, and Yu. Yu. Samitov, Doklady Akad. Nauk S.S.S.R., 1967,174, 846.

38

Organophosphorus Chemistry

7 Miscellaneous Pentafluorobenzaldehyde and trimethyl phosphite in pentane at 0 "C gave32 a mixture of cis- and trans-2: l-adducts from which the pure cis-isomer (40) was isolated by crystallisation. Pseudorotation of this isomer was inhibited at - 130 "C. OMe H MeO. I .I

OMe f-f MeO. I ..

The reaction of diethyl peroxide with acyclic and cyclic phosphites to give pentaoxyphosphoranes has been extended33 to a wide variety of trisubstituted phosphines. The series Ph,P(OEt),,-,, (n = 1, 2, or 3) all gave the expected phosphoranes. Of the phosphines PhnPMe(3-n),that with n = 2 formed a stable phosphorane but the products when n = 0 and 1 appeared to be in equilibrium with the corresponding phosphonium ethoxides, e.g. PhPMe,(OEt),

Ph$Me,(OEt)

-

OEt

Of the aminophosphines Ph,P(NEt,),,-,, that with n = 2 gave a mixture of the phosphoranes (41) and (42) while those with n = 0 and 1 gave only the phosphine oxides. The cyclic aminophosphines (43; R = OEt and NMe,) formed unstable phosphoranes which rapidly decomposed to quadricovalent phosphorus compounds. PhzPNEt,

+ (EtO),

Ph,P(OEt), 3.Ph,P(OEt),(NEt,)

(41)

(42)

Oxadiazaphospholens (44) and (45) were formed 34 from triphenyl phosphite and the azo-compounds shown. An adduct analogous to (44) had previously been obtained 35 from trimethyl phosphite, while the structure of (45) confirmed the analogous formula put forward36 for the triphenyl phosphite-diethyl azodicarboxylate adduct. 3a

33

F. Ramirez, J. F. Pilot, C. P. Smith, S. B. Bhatia, and A. S. Gulati, J. Org. Chem., 1969,34, 3385. D. B. Denney, D. Z. Denney, B. C. Chang, and K. L. Marsi, J. Amer. Chem. SOC., 1969,91, 5243.

34

35

B. A. Arbusov, N. A. Polezhaeva, and V. S. Vinogradova, Izuest Akad. Nauk S.S.S.R., Ser. khim., 1968, 2525. B. A. Arbusov, N. A. Polezhaeva, V. S. Vinogradova, and Yu. Yu. Samitov, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1967, 1605. V . A. Ginsberg, M. N. Vasil'eva, S. S. Dubon, and A. Ya. Yakubovich, Zhur. obshchei Khim., 1960,30,2854.

39

Quinquecovalent Phosphorus Compounds

(44) rj(31P)+71.65 p.p.m.

OEt MeO,C.N:N.CO,Me+ (PhO),P

Ph,P

+

(Me0,C-N :),

___

-

Ph$.N(CO,Me).N.CO,Me

(46)

X

=

C0,Me

OAr 72%

Organophosphorus Chemistry

40

Quinquecovalent phosphorus compounds are implicated as intermediates in the trapping3' of the 1,3-dipolar species (46), formed from triphenylphosphine and dimethyl azodicarboxylate, with methyl propiolate and with 2,6-dimethylphenyl cyanate. The products from the decomposition of pentaphenylphosphorane in the presence of water, phenol, or t-butyl hydroperoxide are consistent 38 with a first step involving loss of a phenyl radical, e.g. Me,CO,H Ph5P

Dioxan

-I- -

' Ph,PO + PhOH + Ph,POPh + 86%

70%

Ph4$6Ph 53O/O 37 3g

llo/o

PhH 87%

+ Me,COH + Me,C:CH, 11%

43 '/o

+ PhH 5 0o/o

E. Brunn and R. Huisgen, Angew. Chem. Internat. Edn., 1969, 8, 513. G. A. Razuvaev, N. A. Osanova, and I. K. Grigor'eva, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 2234.

3 Halogenophosphines and Related Compounds BY J. A. MILLER

1 Halogenophosphines

A. Preparation.-The preparation 1v of fluorophosphines by exchange of fluoride ion with chloride ion in solvents such as acetonitrilel and sulpholan has been reported. Another route to fluorophosphines, involving the reactions of carboxylic acid fluorides with phosphinous amides and phosphonous amides, has been used to prepare diphenylfluorophosphine (1) and difluorophenylphosphine (2). The monofluorophosphine is unstable and was characterised by n.m.r. and by its decomposition products [see B(iii), below]. Ph,PNHPr -II COP11

F

I’hCONI-IPr

___f

+

Ph,PF (1)

T 1

Ph,PNH r’r

Ph,PCI

I’h CO F PhP(r\;Me),

2 PhCONMe,

f PhPFz (2)

Aralkylhalogenophosphines may be prepared in good yield from aralkyl halides and phosphorus trihalides. These react at high temperatures to give aralkyldihalogenophosphines, which disproportionate on distillation in a current of nitrogen to yield monohalogenophosphines (3) and phosphorus t rihalides. I Ar-C-X

I

f

PX,

I (3)

a

a

C. Brown, M. Murray, and R. Schmutzler, J. Chem. SOC.(0,1970, 878. H. W. Roesky, Inorg. Nuclear Chem. Letters, 1969, 5, 891. Y. I. Baranov and S. V. Gorelenko, Zhur. obshchei Khim., 1969,39, 836.

42

Organophosphorus Chemistry

The synthesis of a variety of iododiphosphines has been reported. For example, phosphorus tri-iodide reacts with triphenylphosphine to give tetraiododiphosphine (4, R = I) (together with iodophosphonium salts); and dichlorophenylphosphine and cyclohexyldichlorophosphine give the diphosphines (4, R = Ph and R = C6Hll respectively) on treatment with iodide ion. When the reaction between dichlorophenylphosphine and iodide ion is carried out in benzene, the simple halogen-exchange product, di-iodophenylphosphine, was predominant. Ph3P

+

I I

1 I

+ RP-PR

PI3

f---

RPCI,

(4)

+

I-

I

R = Ph Benzene

PhP12

ButCl

+

PCI,

+

AICI,

___

+ ButPCI3 +

+

C1-

AICI,

Hydrolysis of the complex formed between t-butyl chloride, aluminium chloride, and phosphorus trichloride, failed to give t-butyl dichlorophosphine (5). This phosphine was prepared by desulphurisation of the corresponding sulphide (6j. Two other routes to t-butylphosphines have One involves the controlled displacement of chloride from dichloromethylphosphine by t-butylmagnesium chloride to produce the monochlorophosphine (7), which can then be converted to di-t-butylmethylphosphine under less stringent conditions. The second route starts from t-butyldichlorophosphine and involves the synthesis of the phosphinous amide (8), which is cleaved in the presence of hydrogen chloride to give (7). Treatment of (7) with sodium results in the formation of 1,2-dimethyl-l,2-di-t-butyldiphosphine (9), the n.m.r. spectrum of which indicates that only one diastereoisomer is present in solution. @

*

N. G. Feshchenko, Zh. K. Gorbatenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1969,39, 2596. N. G. Feshchenko, T. V. Kovaleva, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 2184. N. G. Feshchenko, E. A. Melnichuk, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 2139. P. C. Crofts and D. M. Parker, J. Chem. Soc. (C), 1970, 332. W. Kuchen and G. Hagele, Chem. Ber., 1970,103, 2274. 0. J. Scherer and W. Gick, Chem. Ber., 1970, 103, 71.

Halogenophosphines and Related Compounds MePCl,

+

43

ButMgC1

k

20

y

Me P(13ut),

BU'M~C~

OC

Me--P

,But 'CI

(i) Et,NH (2 equiv.)

But P CI,

B. Reactions.-(i) Nucleophilic Attack at Phosphorus. Diary1 sulphides l o and ethers l1can be converted into phosphorus heterocycles (10, R1 = OH or alkyl; X = S or 0) of potential pharmaceutical interest, by reaction with aluminium chloride and phosphorus halides, followed by hydrolysis.

(R,

=

C1, alkyl)

The hydrolysis l2 of chlorodi-t-butylphosphine results in the formation of di-t-butylphosphine oxide, which is extremely stable to oxidation and to treatment with alkali. Aryldichlorophosphines are converted l3 to aryldialkylphosphine oxides (1 1) by successive treatment with iodide ion and an alkyl halide, followed by hydrolysis of the intermediates. ' 9

ArPCI,

I)

r-

(ii) RX

[ArR,PI,l

0 11 ---+ A r P R , H20

(50-7'573

(1 1)

A variety of anions will displace l4 chloride or bromide ion from difluorohalogenophosphines to give substituted difluorophosphines (1 2, Y = CN, CF,CO, or -NCO). An unusual reduction, of 2-bromocyclohexanol(l3) to lo

l1 la

l4

1. Granoth, A. Kalir, Z. Pelah, and E. D. Bergmann, Tetrahedron, 1969, 25, 3919. I. Granoth, A. Kalir, Z . Pelah, and E. D. Bergmann, Tetrahedron, 1970, 26, 813. A. P. Stewart and S. Trippett, J . Chem. SOC.(0,1970, 1263. N. G. Feshchenko, T. V. Kolaleva, and A. V. Kirsanov, Zhrn. obshchei Khim., 1969, 39, 2188. G . G . Flaskerud, K. E. Pullen, and J. M. Shreeve, Znorg. Chem., 1969, 8, 728.

Organophosphorus Chemistry

44

39%

36X

(13)

monobromocyclohexanol with phosphorus tribromide, is reported l5 to compete with the expected bromination to give 1,2-dibrornocyclohexanol. The first step in the complex reactions of tertiary phosphines with halogenophosphines is the formation 1 6 ~l7 of the phosphonium salts (14), and the factors which determine the further reactions of (14) to give R13P 4-

R2,PCl

PhzPCI

4

[R1,P-PR2,]+

-t PhXH

__j

CI-

Ph2P-Xph (1 7)

phosphoranes (1 5) or diphosphines (1 6) have been In general, simple trialkylphosphines give only adducts of type (14), but bulky trialkylphosphines and triarylphosphines give products containing phosphorusphosphorus bonds. Chlorodiphenylphosphine has been converted into the thio- and seleno-phosphines (17, X = S, and X = Se respectively). Phosphorus trichloride reacts l9 with hydroxylamine and hydrazine derivatives to give substituted chlorophosphines, which with sodium fluoride or antimony trifluoride give the corresponding substituted fluorophosphines (18, n = 1 or 2, X = OR or NR2). The reaction of methylhydrazine with bis(trifluoromethy1)iodophosphine gives 2o comparable amounts of (19)and (20). Treatment of halogenophosphines with imidates produces 21N-phosphinoimidates(21,R1= OEt or NMe, ;R2 = alkyl or aryl). l6 l7

*O

a1

G. Bellucci, F. Marioni, A. Marsili, P. L. Barili, and G. Berti, Chem. Comm., 1969, 1017. S. F. Spangenberg and H. H. Sisler, Znorg. Chem., 1969, 8, 1006. J. C. Summers and H. H. Sisler, Znorg. Chem., 1970, 9, 862. R. A. N. McLean, Znorg. Nuclear Chem. Letters, 1969, 5 , 745. A. E. Goya, M. D. Rosario, and J. W. Gilje, Inorg. Chem., 1969, 8, 725. L. K. Petersen and G. L. Wilson, Canad. J . Chem., 1969, 47, 4281. Y. Charbonnel, J. Barrans, and R. Burgada, Bull. SOC.chim. France, 1970, 1363.

-

Halogenophosphines and Related Compounds PCI,

+

RNHX

45

CI,P(NRX),-,

NaFl

(or SbF,)

F,P(NRX),(1 8)

+

,OMe

R1,PCI

4-

HN=C,

R1,P-N=C

___f

,OMe \

R2

RZ

(ii) Electrophilic Attack at Phosphorus. Conjugate addition reactions of a number of halogenophosphines have been reported. Chlorodialkylphosphines add 22 to 2-vinylpyridine to produce orange adducts, which decompose in the presence of proton donors, such as alcohols, to give 2-(~-dialkylphosphinyl)ethylpyridines(22). The quantitative formation 23 of a phosphorus-containingpolymer from chlorodiethylphosphine(23) and methyl acrylate can be similarly rationalised.

+ R1,PCl

+

I

[Et, PCH,CHCO,Me 1

I

aa

+

nCl-

V. S. Tsivunin, L. N . Krutskii, T. V. Zykova, and G. K. Kamai, Zhur. obshchei Khim., 1969,39,2666.

33

V. S. Tsivunin, S. K. Nurtdinov, R. R. Shagidullin, and G. K. Kamai, Zhur. obshchei Khim., 1969, 39, 1561.

46

Organophosphorus Chemistry

The formation 24 of (24) from chlorophosphines (25) and acrylamide has been explained on the basis of a conjugate addition by the phosphine, followed by phosphorane formation, since the rate of reaction of (25) decreases as R = alkyl, R = aryl or R = chlorine. Similar reactions of dichlorophosphines have previously been reported.25,26 -

c1*\C/NH2 I<,PCl (25)

+

+

CH2’CHCONHz

I I/ w, + c,CH H2

c1

0 It R2I’CH,CH,C=N

f------

(24)

I p-c II

K,P

,NH2

\CNCH Hz

Halogenophosphines can be converted 27 into phosphine oxides by reaction with trialkylboranes. For example, cyclohexyldiphenylphosphine oxide (26, R = C6Hll) was obtained in 57% yield by the reaction shown. 0 R3B

-I- Ph,PCl

[R3B.PPh2CIl

I/

[*It

PhzPR

(26)

(iii) Miscellaneous. A study

of the disproportionation of diphenylfluorophosphine to diphenyltrifluorophosphor ane (27) and t etraphenyldiphosphine [in contrast to the stability 23 of fluorobis0pentafluoropheny1)phosphinel has led to the suggestion of a mechanism involving both electrophilic and nucleophilic phosphorus. There appears to be some 2 Ph2PF

F I . + Ph,P-PPh,

+

F

-I-

F-

I + Ph,PPPh, I

F

p,,P,

Ph,I’PPh,

+

Ph,PF3 (27)

24

25

2e

27

Ph I+ + Ph,P-P-PPh,F, I PI1

+

F-

A. N. Pudovik and V. K. Khairullin, Zhur. obshchei Khim., 1969, 39, 1724. V. K. Khairullin, R. M. Kondrateva, and A. M. Pudovik, Izvesr. Akad. Nauk S.S.S.R., Ser. khim., 1967, 2097. V. K. Khairullin, T. I. Sobchuk, and A. N. Pudovik, Zhur. obshchei Khim., 1968, 38, 584. P. M. Draper, T. H. Chan, and D. N. Harpp, Tetrahedron Letrers, 1970, 1687.

47

Halogenophosp hines and Related Compounds

controversy about the stability,l. 2 B ~30 and the degree of polymerisation of the decomposition products 29, 30 of difluorophenylphosphine, which has been reported to form phenylphosphines, (PhP), with rz = 5,2Band also to form a polymeric p h ~ s p h i n e . ~ ~ The reactions of chlorodiphenylphosphine with t-butylperoxy-esters (28, R = COMe or COPh) give 31 very complex mixtures of products, which may be the result of homolytic processes, since cupric bromide is a catalyst. The analogous reaction of t-butyl hydroperoxide in pyridine gives rise 33 to diphenylphosphinic acid (29, R = H) and t-butyl diphenylphosphinite (29, R = But). Sulphoxides are cleanly reduced33 to sulphides by treatment at room temperature with phosphorus trichloride. A simple method for the oxidation of chlorophosphines using oxygen has been described.34 Treatment of diacetone alcohol with dichlorophenylphosphine in the presence of triethylamine gives 35 the phosphinate (30), in which JPH*and J P H ~are equal. This is taken as evidence for the fact that the carbon atoms and the phosphorus atom in the ring are coplanar. 28j

0

ROOBut (28)

+

Ph,PCl or

i = c Ro= CdO M e (

7)

0 I1

Ph,P 2O R,O

+

+

Ph,POH

RCl

+

+

ROH

ButCl

+

F

The formation of adducts of type (31) from phosphorus trichloride and heptamethyldisilazane, in 1 : 1 ratio, has been established36as a general reaction. Previous reports 37 of such reactions had suggested that the as 30

31 32 33 34

35 86

M. Fild and R. Schmutzler, J . Chem. SOC.( A ) , 1969, 840. A. Finch, P. J. Gardner, A. Hameed, and K. K. Sen Gupta, Chem. Comm.,1969, 854. H. G. Ang and R. Schmutzler, J. Chem. SOC.(A), 1969, 702. G. Sosnovsky and D. J. Rawlinion, J . Org. Chem., 1969,34, 3462. G. Sosnovsky, E. H. Zaret, and K. D. Schmitt, J . Org. Chem., 1970,35, 336. I. Granoth, A. Kalir, and Z . Pelah, J. Chem. SOC.(C), 1969, 2424. A. N. Smirnov and A. P. Khardin, Zhur. obshchei Khim., 1969, 39, 2138. K. Bergesen, Acta Chem. Scand., 1969, 23, 696. R. Jefferson, J. F. Nixon, and T. M. Painter, Chem. Comm., 1969, 622.

48

Organophosphorus Chemistry products were diazadiphosphetidines (32), the pentacovalent phosphorus analogues of which are formed 38 in reactions of phosphorus pentafluoride. The i.r. and Raman spectra of dichlorophenylphosphine and chlorodiphenylphosphine have been s t ~ i d i e d . ~ ~ ,PCI,

(Me3Si),NMe

+

/ PCI,

Me”,

PCl, (31) ‘.k, Me CI ’N - P‘

I

+

2(Me3SiC1)

I

/p -N, c1 (32)

Me

2 Halogenophosphoranes A. Structure and Spectra.-The reaction of heptamethyldisilazane with phosphorus pentafluoride is known 38 to give (33) whose structure has now been confirmed 40 by electron-diffraction. The N-methyl groups, and the axial fluorines, all lie in the plane of the ring. A more satisfactory value for the 31P-shift (+80.3 p.p.m.) and JPF (938 Hz) of phosphorus pentafluoride has been e~tablished.~~ Previous shifts had, in error, been measured on phosphorus oxyfluoride, formed by hydrolysis of the pentafluoride. The first unsubstituted aminofluorophosphorane has been prepared,42 from phosphorus pentafluoride and ammonia, and its structure has been established as (34), largely on the basis of its n.17n.r. spectrum, which shows the two amino-groups to be equatorial. A study43of the line-broadening of the n.m.r. spectrum of dimethylaminotetrafluorophosphorane (35) during pseudorotation has demonstrated that the exchange of both axial fluorines with both equatorial fluorines occurs simultaneously. This observation thus confirms one of the distinguishing predictions of Berry’s theory of positional exchange by pseudorotation. Other studies 44-48 of the n.m.r. spectra of fluorophosphoranes are discussed in Chapter 11. a8

38 40

4l

ra 43

44

46 46

E. W. Abel, D. A. Armitage, and G. R. Wiley, J , Chem. Soc., 1965, 57. R. Schmutzler, Chem. Comm., 1965, 19. J. H. S. Green and W. Kynaston, Spectrochim. Acta, 1969, 25A, 1677. A. Almehningen, B. Andersen, and E. E. Astrup, Acta Chem. Scand., 1969, 23, 2179. L. Maier and R. Schmutzler, Chem. Comm., 1969,961. M. Lustig and H. W. Roesky, Inorg. Chem., 1970, 9, 1289. G. M. Whitesides and H. L. Mitchell, J. Amer. Chem. SOC.,1969, 91, 5384. G. I. Drozd, M. A. Sokal’skii, V. V. Sheluchenko, M. A. Landau, and S. Z. Ivin, Zhur. obshchei Khim., 1969, 39, 935. G. I. Drozd, M. A. Sokal’skii, V. V. Sheluchenko, M. A. Landau, and S. Z. Ivin, Zhur. obshchei Khim., 1969, 39, 936. M. A. Sokal’skii, G. I. Drozd, M. A. Landau, and S . S . Dubov, Zhur. strukt. Khim., 1969, 10, 1113.

Halogenophosphines and Related Compounds

49

Me I

F

I ...F Me2N- , P

kF

I

Me

(35)

(33)

B. Reactions.-The reactions of halogenophosphoranes with amines, phosphines, and thiols continue to be investigated. Alkylamines react 47 with phosphorus pentafluoride in the absence of solvent to give alkylaminotetrafluorophosphoranes (36), bis(alky1amino)trifluorophosphoranes (37), and akylammonium hexafluorophosphates (38). A previous paper 48 on the same reaction, carried out in solvent, reported the formation of diazadiphosphetidines. Treatment 49 of diphenyltrichlorophosphorane with alkylamines leads to phosphonium salts, (39), and reaction with amides produces iminophosphoranes (40).

0 11

Cl

I

Ph?P=N-C-R (40)

RCONTI, y" Ph,PCI3

RNH,

---+

CI I RNHTPh,

CI'

(39)

Alkyl- and aryl-thiofluorophosphoranes(4 1) have been synthesised 61 from alkyl- and aryl-thiosilanes, in reactions which are rather unusual because of the difficulty of introducing more than one sulphur-containing group into the product. The phosphoranes 141) were found 6o to be somewhat unstable, but analysis of their n.m.r. spectra showed non-equivalent axial fluorines, believedso to be the effect of hindered rotation about the sulphur-phosphorus bond. 6om

47 4B 48

so

J. S. Harman and D. W. A. Sharp, J. Chem. SOC.( A ) , 1970, 1138. J. J. Harris and B. Rudner, 3. Org. Chem., 1968, 33, 1392. W. Haubold and M. Becke-Goehring, 2. anorg. Chem., 1970, 372, 273. S. C. Peake and R. Schmutzler, J . Chem. SOC.(A), 1970, 1049. D. H. Brown, K. D. Crosbie, J. I. Darragh, D. S. Ross, and D. W. A. Sharp, J.Chem. SOC.(A), 1970, 914.

50

Organophosphorus Chemistry

Conductimetric titration has been used 6 2 to follow the reactions between phosphorus pentachloride and triphenylphosphine, which finally result in the quantitative formation of conducting solutions of (42).

+

Ph,P

Ph,PCl,

PC1,

+

--

PCI,

+

Ph,PCI, Ph,$C1

PCI,

PCI,

(42)

The conversion of alcohols into alkyl chlorides by treatment with triphenylphosphine in carbon tetrachloride has been shown to result 69 in almost total inversion when optically active alcohols are used. The same stereochemical feature has also been reported 64 with 7-hydroxybicyclo[2,2,l]hexane systems, and this has been rationalised in terms of a phosphorane intermediate (43), in which the phosphorus-chlorine bond breaks before the carbon-oxygen bond, to produce an intimate ion-pair which gives the observed products. Ph,P

+

CCl,

---+ Cl3C

+

f Ph,PCl

ROH

Ph,P(OR)CI

c1 I

Dibromotriphenylphosphorane (44) reacts with secondary amines to form 55 aminophosphonium salts, which on treatment with base give imines. Aziridines are formed66 in fair yield when (44) is treated with /3-amino-alcohols in the presence of base. Studies with threo- and erythroephedrine have indicated that the reaction involves an inversion at the alcoholic carbon, and this has been explained 66 as resulting from nitrogencarbon bond formation in the phosphonium intermediate (45), rather than in the phosphorane (46). 5B

53 64

55 66

V. G. Rozinov, E. F. Grechkin, and A. V. Kalabina, Zhur. obshchei Khim., 1969, 39, 712. D. Brett, J. M. Downie, J. B. Lee, and M. F. S. Matough, Chem. and Ind., 1969, 1017. R. G. Weiss and E. I. Snyder, J. Org. Chem., 1970, 35, 1627. K. Fukui and R. Sudo, Bull. Chem. SOC.Japan, 1970,43, 1160. I. Okada, K. Ichimura, and R. Sudo, Bull. Chem. SOC.Japan, 1970, 43, 1185.

51

Halogenophosphines and Related Compounds Ph,PBr,

-I- PhCH,NHMe

+ Ph,;N(Me)CH,Ph

Br-

(44)

Ph3P

+

PhCH=NMe

+

Ph3Br2

+

1

1

I

I

Ph,P=O

HO-C-C-NHMe

+

\

"3

Me-Nd

Ph ... 1 ,P-N Ph I \ Ph Me (46)

The phosphorane (47) gives l-phenyl-3,4-dimethylphospholewith 1,5-diazabicyclo[5,4,0]undec-5-ene (DBU) and 1-phenyl-3,4-dimethylphosphol-3-ene on treatment with butyl-lithium. The preparation of 1-phenylphospholes by this route compares favourably with previous methods. Phosphorus pentachloride has been used to replace 68 benzylic hydrogens with chlorine in high yield; e.g. toluene is converted to benzyl chloride (9779, by heating at 200 "C for 18 h with phosphorus pentachloride. The conditions used in the previously reported formation of (48) from phosphorus pentachloride and NN-diethylbromoacetamidehave resulted 6o in the isolation of the chlorine analogue (49).

BrCrCNEt, (48)

f--

BrCH,CONEt,

-I- PCI,

+ ClCH,CONEt,

(49)

p-Alkoxyvinylphosphonic acid derivatives (50, Rlj = aryl, R2 = Me, X = OH) result 61 from the addition of phosphorus pentachloride to 19-methoxystyrenes, followed by hydrolysis of the intermediate adducts. 57 58

6*

eo

F. Mathey, Compt. rend., 1969, 269, C, 1066. R. D. Kimbrough and R. M. Bramlett, J. Org. Chem., 1969,34, 3655. Y . Y . Tsmur and V. I. Ivanik, Zhur. obshchei Khim., 1963,33, 1697. R. I. Kruglikova, G. R. Kalinina, and G. N. Solol'skaya, Zhur. obshchei Khim., 1969, 39, 1183. V. G. Rozinov and E. F. Grechkin, Zhur. obshchei Khim., 1969, 39, 934.

52 Organophosphorus Chemistry The formation62of similar products (50, R1= R2 = alkyl, X = C1) from the reaction of phosphorus pentachloride with simple alkyl chloroalkyl ethers has been suggested to be the result of dehydrohalogenation of the initial ethers, to give vinyl ethers to which the phosphorus pentachloride adds in the usual fashion. C1

I

R20CHCH2R1

-

[R20CH=CHR11

I

0

/PCI, R20CH=C, -

MeOCH = CH - Ph

3 Phosphines Containing a P-X Bond (X = Si, Ge, Sn, or Pb) Two reviews containing sections on the above phosphine compounds have 64

A. Preparation.-The preparation 66 of lithium tetraphosphinoaluminate (51) and its application 66v 66 to the synthesis of silylphosphines and germylphosphines is reported. In general, the reactions of (51) with halogenosilanes and halogenogermanes are carried out at low temperatures, and it can be used together with lithium aluminium hydride, in which case silylphosphines containing silicon-hydrogen bonds are formed. , Me,SiClz

LiAI(PH2), LAH> Me,Si(PH,)H (51) e GeBr (36%) Me,GePH2 (76%)

Lithium diethylphosphide has been used6' in a general preparation of silylphosphines of type (52), and good yields obtained when the silyl chloride is present in excess. Base-catalysed condensation of methylphosphine with trimethylstanAy1 chloride gives68 methyLbis(trimethy1stanny1)phosphine (53). (Trimethylstanny1)di-t-butylphosphine (54) has V. G . Rozinov, A. L. Taskina, and E. F. Grechkin, Zhur. obshchei Khim., 1969, 39 1647.

68

65

66

*'

H. Schumann, Angew. Chem. Internat. Edn., 1969, 8, 937. E. W. Abel and S. H. Illingworth, Organometallic Chem. Rev., 1970, A5, 143. A. D. Norman and D. C. Wingeleth, Inorg. Chem., 1970, 9, 98. A. D. Norman, Inorg. Chem., 1970, 9, 870. G. Fritz, G . Becker, and D. Kummer, Z . anorg. Chem., 1970, 372, 171. H. Schumann and U. Arbenz, J. Organornetallic Chem., 1970,22,411.

53

Halogenophosphines and Related Compounds

been prepared 6B from di-t-butylphosphine, and a variety of phosphines (55, M = Ge, Sn, or Pb; n = 1 or 2) from phenylpho~phines.'~ Et,PLi

+

R,SiCl,-,

R,Si(PEt,),-,

(52) Me3SnC1 -I- MePH2

--+

(Me,Sn),PMe

(53) Me3SnNMe,

+

(But),PH 4 Me3SnP(But),

+

Me,NH

(54)

B. Reactions.-The disproportionation 71 reactions of a number of silylphosphines have been studied, and generally found to involve the exchange of substituents on silicon, so that similar ligands tend to become attached to the same silicon atom, e.g. disproportionation of diethylsilylphosphine (56) and chlorosilyldiethylphosphine(57). Other silylphosphines, such as methylsilyldiethylphosphine (58), are quite stable.

3 H,SiCI(PEt,)

--+

C13SiPEt,

+

2 H,SiPEt2

(57)

Silylphosphine reacts 72 with halogenogermanes to form germylphosphines. The phosphorus-silicon bond of tris(trimethylsily1phosphine)(59) is cleaved 73 by chloramines, to give chlorotrimethylsilane. The reactions 7 4 of nitrosyl chloride with trimethylsilyldimethyl-phosphine,-arsine, and -amine result in cleavage of the bond between silicon and the Group V element. However, the reaction products of the phosphine (60, M = P) are considerably more complex than those of the amine (60, M = N). 6s 'O

71 72

73 74

H. Schumann, L. Rosch, and 0. Stelzer, J . OrganometaIlic Chem., 1970, 21, 351. H. Schumann, R. Schwabe, and 0. Stelzer, Chem. Ber., 1969,102,2900. G . Fritz and G. Becker, 2. anorg. Chem., 1970, 372, 196. J. E. Drake, N. Goddard, and C. Riddle, J . Chem. Suc. (A), 1969,2704. R. E. Highsmith and H. Sisler, Inorg. Chem., 1969, 8, 1029. J. R. Byrne and C. R. Russ, J . Organometallic Chem., 1970, 22, 357.

3

54

Organophosphorus Chemistry (Me3Si)3P

+

--+

3RzNCI

(R,N),P

+

Me,SiCl

+

Me,N-N=O

Me,SiC1

+

(Me,Si),O

3Me3SiC1

(59)

Me,SiMMe,

+

NOCI

(60)

1

+ Me,PCI II 0

The reactions 76 of silylphosphines with methyl-lithium and lithium diphenylphosphide have been described. These reagents form new siliconcarbon, and silicon-phosphorus or hydrogen-phosphorus bonds, as illustrated for (61) and (62). MeH,Si(PEtz)3-, M

e

+

LiPEt,

y

H,Si(PEt2)4-,

YHPEt,

(61)

MeSiH,(PEt,)

(62) 76

3.

2LiPEt,

+

LiSiH,-,(PEt),,,

4 2LiH

*

G. Fritz and G . Becker, Z. anorg. Chem., 1970,372, 180.

-I- MeSi(PEt,),

4 Phosphine Oxides BY J. A. MILLER

1 Preparation A. Using Organometallic or Complex Hydride Reagents.-Treatment of phosphonic acid dihalides with bulky Grignard reagents does not yield significant amounts of the expected tertiary phosphine oxides (l).l The major products are secondary phosphine oxides (2). The reaction of optically pure menthyl phosphinates (3) with alkyl or aryl magnesium halides gives tertiary phosphine oxides with high optical purity,2 although the reaction is subject to limitations, probably steric in nature. These limitations may be overcome by the use of alkyl lithium reagents,2although the optical purity of the phosphine oxides is poorer than that found with Grignard reagents. 0

ButMgX

+

II RPCIP

*

0 II RPBut2

0

+

II

RPHBut

(R = Me, 2%)

(R = Me, 23%)

(1)

(2)

0

II RPR1R2

0 I/

(4)

R'

= Ph,

R2 = /I-Cl,H,

[a]D = - 0.59"

Another example of the reduction of an optically active menthyl phosphinate by lithium aluminium hydride to give an optically active secondary phosphine oxide has been r e p ~ r t e d . The ~ product (4) has a very small rotation, in common with other oxides produced by this method. A. D. Brown and G. M. Kosolapoff, J. Chem. SOC.(C), 1968, 839.

* R. A. Lewis and K. Mislow, J . Amer. Chem. SOC.,1969, 91, 7009.

0. Cervinka, 0. Belovsky, and M. Hepnerova, Chem. Comm., 1970, 562. T. L. Emmick and R. L. Letsinger, J . Amer. Chem. SOC.,1968,90, 3459.

56 Organophosphorus Chemistry B. From Alkyl Phosphinites.-Ethyl diphenylphosphinite ( 5 ) can displace nitro-groups from dinitrobenzenes to give aryldiphenylphosphine oxides by a novel variant of the Arbusov reaction. This reaction is a considerable contrast to the usual deoxygenation reactions of nitro-compounds with tervalent phosphorus reagents. Ph,POEt

aNo2 aNo2

-+

+

EtONO

PPhz

NO2

II

0

Several examples '-O of the preparation of the elusive lo a-ketophosphine oxides have appeared. The oxides (6, R = alkyl, R1 = Me) have been synthesised from acetyl chloride, and the oxide (6, R = But, R1 = Ph) from benzoyl chloride. Characterisation of a-ketophosphine oxides as dialkylphosphorodithioate derivatives has been reported.* , The attempted preparation l1 of trifluoroacetyldiphenylphosphine oxide (6, R = Ph, R1= CF3), by oxidation of the phosphine, resulted in the isolation of the oxide (7), believed12 to be formed by the reaction of (6, R = Ph, R1 = CFs) with traces of water in the reaction system to form diphenylphosphine oxide, and addition of this to (6, R = Ph, R1= CF,). 0 II

Ph2P-CH-

0 II O-PPh2

0 0 (7)

S II -----.JRzo)~PsH

o II

(6)

OH

I

s I1

R,P-C-SP(OR2)2 I

R'

Details have appeared l4 of the preparation of a-diazoalkyldiphenylphosphine oxides (8) from diphenylphosphinite esters. The preparation of a range of diphosphine oxides (9) by Arbusov reactions has been reported.15 An unusual, hydrogen-chloride-catalysed, cleavage of the 139

(I

@

lo l1

la lS l4 l6

J. I. G. Cadogan, D. J. Sears, and D. M. Smith, J. Chem. SOC.( C ) , 1969, 1314. J. I. G. Cadogan, Quart. Rev., 1968, 22, 222. A. P. Stewart and S. Trippett, J. Chem. SOC.(C), 1970, 1263. V. S. Abramov and N. I. D'yakonova, Zhur. obshchei Khim., 1969,39, 630. Y . Ogata and H. Tomioka, J . Org. Chem., 1970,35, 596. R. S. Davidson, R. A. S h q o n , and S. Trippett, J. Chem. SOC.(C), 1968, 1700. E. Lindner, H.-D. Ebert, and P. Junkes, Chem. Ber., 1970, 103, 1364. E. Lindner, H.-D. Ebert, and A. Haag, Chem. Ber., 1970, 103, 1872. M. Regitz, W. Anschutz, W. Bartz, and A. Leidhegener, Tetrahedron Letters, 1968, 3171. M. Regitz and W. Anschiitz, Chem. Ber., 1969, 102, 2216. Y . I. Baranov, S. V. Gorelenko, and S . P. Kochkol'da, Zhur. obshchei Khim., 1969,39, 839.

57 phosphinite (10) to give methyltrifluoromethylphosphine oxide (1 1) has been rationalised l6 as an Arbusov-type reaction, in which the oxygencarbon bond of (10) breaks as the result of protonation.

Phosphine Oxides

0

Ph2POR1

I1

+

(R

RCHzX ---+ PhZPCH2R =

i BuLi

0 II Ph2PC(N,)R

Ph ,CR2)

I1

0

(10)

(11)

C. By Addition Reactions of Secondary Phosphine Oxides.-@ To Carbonyl. There has been a report l7 of improved yields in the reactions of aldehydes with halogenophosphines, in the presence of water, to produce a-hydroxyalkyldiphenylphosphine oxides (12). The reaction fails in the case of R = anisyl, when (13) is isolated. The anomalous behaviour of a-hydroxybenzylphosphine oxides with an electron-donating group in the p-position of the benzyl group had been observed previously.18 Di-t-butyl-phosphine oxide does not add to carbonyl c o m p o ~ n d s . ~

c1 0

0 RCHO

+

II

Ph,PH

PhzPCl

( R = anis'') HCI

I

f

II

RCH-PPh

2

OH 0 I II RCH- PPh (12)

The addition of dialkyl and alkyl-aryl secondary phosphine oxides to a variety of carbonyl compounds has been reported,ls~ 2o and the rearrangement of the resultant a-hydroxyalkyldialkylphosphine oxides studied in l7 la

2o

A. B. Burg and Dae-Ki Kang, J. Amer. Chem. SOC.,1970,92, 1901. R. S. Marmor and D. Seyferth, J. Org. Chem., 1969, 34, 748. R. S. Davidson, R. A. Sheldon, and S. Trippett, J. Chem. SOC.( C ) , 1967, 1547. A. N. Pudovik, I. V. Gur'yanova, M. G. Zimin, and A. V. Durneva, Zhur. obshchei Khim., 1969, 39, 1018. V. S. Abramov, N. I. D'yakonova, and V. D. Efimova, Zhur. obshchei Khim., 1969, 39, 1971.

58

Organophosphorus Chemistry

detail. Of particular interest is the thermal rearrangement lo of the oxides (14, R = Me or Ph), to the esters (15, R = Me or Ph). These reactions involve 0 0 II II R*C--P(OEt),

+

0 II Bu2PH

+

HO 0 I II RC-P(OEt), I

O=PBu,

0 II R-CH-0-PBu, I 0 =P (OEt), (15)

an apparent three-centre rearrangement in which only the dialkylphosphinyl group migrates from carbon to oxygen, and for which the rate increases from (14, R = Me) to (14, R = Ph). (ii) To Other MuZtipZe C=X Bonds. The addition of diarylphosphine oxides to isothiocyanates to give the adducts (16) has been reported.21 The formation of three adducts (17), (18), and (19) of tetracyclone and diphenylphosphine oxide has been rationalised 22 in terms of (17) being the product of the kinetically controlled reaction, and (18) and (19) the products of the thermodynamically controlled reaction. 0 II Ar,PH

0 s

+

R-N=C=S

+

---+

II II Ar,P-CNHR

Ph2PH

Ph 0

(18) R = H, R' = Ph (19) R = Ph, R1= H 21 22

0

I. Ojima, K. Akiba, and N. Inamoto, Bull. Chmi. SOC.Japan, 1969, 42, 2975. J. A. Miller, Tetrahedron Letters, 1969, 4335.

Phosphine Oxides 59 D. Miscellaneous.-The preparation of phosphine oxides by the hydrolysis of phosphonium salts, and by the hydrolysis of halogenophosphines and halogenophosphoranes, is discussed in detail in Chapters 1 and 3 respectively. Treatment of triphenylphosphine or tributylphosphine with hydroxylamine (in the absence of air) leads23to the unexplained formation of the corresponding phosphine oxides. An unusual one-step formation of a secondary phosphine oxide (20) directly from phosphorus by its electrolytic reduction in the presence of cyclohexanone has been

(20)

Further applications of the thermal rearrangement of a-alkynylphosphinites to allenic phosphine oxides are 26 Studies of the n.m.r. spectra of the products show the rearrangement to be stereospecific, e.g. the ester (21) rearranges to the phosphine oxide (22). The synthesis of 0

A __j

(22) CH,OH R2PCH2OH

+

CICH2CO2Et

+

I

K,PCH,C02Et

+

C1-

]Eta.

K,P CH2COZEt

1

[OI

0 II K, PCH,CO,Et

23 24 26

2e

M. D. Martz and L. D. Quin, J . Org. Chem., 1969, 34, 3195, M. Osadchenko and A. P. Tomilov, Zhur. obshchei Khim., 1969,39, 469. J. P. Battioni and W. Chodkiewicz, Bull. SOC.chim. France, 1969, 98 1, A. Sevin and W. Chodkiewicz, Bull. SOC.chim. France, 1969, 4016.

60 Organophosphorus Chemistry phosphine oxides from hydroxymethylphosphonium salts, by treatment with base, then oxidation, continues to be of general use, e.g. in the preparation of (23).27 2 Reactions A. Nucleophilic Reactions of P=O and P=S Groups.-Outstanding progress has been made towards a better understanding of the mechanism of the reduction of phosphine oxides and sulphides to phosphines using silicon reagents. In a study of the reducing reactions of hexachlorodisilane (24), a rationalisation has been suggested 28 for the fact that phosphine oxides are reduced with inversion of configuration at phosphorus, whereas phosphine sulphides are reduced with retention of configuration.2s This involves the mode of breakdown of the intermediate (25), formed by

R'

\

R2-P=X

-t

/

R3

C13SiSiC13 (24)

R1

\+

R2-P-X-SiC13 / R3

SiCI,

+/ R'

---+

x=o

+

CI,Si-P-R2 \

R1

R1

\

R2-P RJ

6SiC13

R3

+

CI3SiSSiC13

CI3SiOSiCl3

+

/

P-R2 \ R3

nucleophilic attack of either phosphine oxides (X = 0) or sulphides (X = S) at silicon. When X is oxygen, the trichlorosilicon anion attacks at phosphorus (with inversion), and when X is sulphur, the sulphur is attacked and configuration at phosphorus is retained. The preparative use of the reduction of phosphine oxides is discussed in Chapter 1. The catalysis of the conversion of phenyl isocyanate (26) to diphenylcarbodi-imide by tertiary phosphine oxides has been investigated in detail,30 27 28

so

K. A. Petrov, V. A. Parshina, and G . M. Petrova, Zhur. obshchei Khim., 1969,39, 1247. K. Naumann, G. Zon, and K. Mislow, J. Amer. Chem. Soc., 1969,91, 7012. G. Zon, K. E. Debruin, K. Naumann, and K. Mislow, J . Amer. Chem. SOC.,1969,91, 7023. G. Aksnes and P. Froyen, Acta Chem. Scand., 1969, 23, 2697.

Phosphine Oxides

61

and been shown to be the result of nucleophilic attack by the phosphine oxide on (26) to produce a phosphine imine (27), which then reacts similarly. R3P=O

+

--

t-

R3P-O

7

I

--

R3P-0 I I PhN-C=O

PhN=C -0

-

Ph-N=C=O

R,P=NPh

+

PhN=C=O

CO,

+

R,P=NPh

7

+ R3P-NPh O-&=NPh

--

R,P-NPh

I

1

0-C=NPh

-

R,P=O

PhN=C=NPh

Studies have appeared of the protonation of phosphine oxides by perchloric acid in n i t r ~ m e t h a n e ,and ~ ~ of the complexes formed in nitrobenzene between a selection of phosphoryl compounds and acceptors such as antimony pentachloride and boron t r i ~ h l o r i d e . ~ ~ The formation of alkoxyphosphonium salts (28) by alkylation of phosphoryl compounds with triethyloxonium salts has been studied, and an attempt made to correlate33 the formation of (28) with (i) 31P shift, (ii) methyl 7-value, and (iii) i.r. P=O absorption, of the parent phosphoryl compounds. The methyl 7-values and the P=O absorptions were found to be reasonably good criteria for the formation of (28).

B. Electrophilic Reactions.-The alkaline hydrolysis of l-phenylphospholan1-oxides does not appear to be controlled by the stereochemical features of the five-membered ring, since the oxide (29) gives acids (30) and (31) These reactions thus conwhen R = Ph and R = C6Hll re~pectively.~~ form to the trend well established for acyclic oxides, when the preferred carbanion is generally displaced. The phosphetan-1-oxide (32) ring-opens with phenyl-lithium to give the secondary phosphine oxides (33),35 presumably via a cyclohexadienate anion, which can be quenched by water to give (33, R = H) or by methyl iodide to give (33, R = Me). 31 32

33

34

35

B. I. Stepanov, B. A. Korolev, and A. I. Bokanov, Zhur. obshchei Khim., 1969,39, 316. V. Gutmann and J. Imhof, Monatsh., 1970, 101, 1. L. V. Nesterov, A. Y. Kessel, Y. Y. Samitov, A. A. Musina, and G. N. Romanova, Zhur. obshchei Khim., 1969, 39, 2457. B. R. Ezzell and L. D. Freedman, J. Org. Chem., 1970,35,241. W. Hawes and S. Trippett, J. Chem. Soc. (0,1969, 1465.

62

Organophosphorus Chemistry 0 II

Ph-P-CH(

I

Ph)CH,CH, CH,Ph

OH (30)

PhH

+

M e g P h 0

(32)'

(33)

I': 1

Li AI(OPRR1R2)a

The stereomutation of phosphine oxides by lithium aluminium hydride has been explained36by the formation (and pseudorotation) of the phosphorane (34) by attack of hydride at phosphorus in the complexed oxide. Sodium methoxide in methanol has been shown3' to displace the pentafluorophenyl group efficiently from pentafluorophenyldiphenylphosphine oxide (35, X = 0), although with the corresponding sulphied (35, X = S) attack at phosphorus is a minor reaction. X

II

Ph *PC,F,

(35)

X MeONa-MeOH

I1

Ph ,P OMe

(X = 0, 100%) (X = S, 25%)

C. Reactions not Involving P=O and P=S Groups.-The chemistry of a-diazophosphine oxides has been the subject of recent attention. The photolysis of (36) leads 38 to a-phosphinyl carbenes, which undergo the standard reactions of solvent insertion to give (37), and trapping with cyclohexene to give products of insertion (38) and of addition (39). When (36, R = Ph or COPh) is photolysed, the W O E rearrangement product (40) predominates. s6

s7

P. D. Henson, K. Naumann, and K. Mislow, J. Amer, Chem. SOC.,1969, 91, 5645. J. Burdon, I. N. Rozhkov, and G. M. Perry, J . Chem. SOC.( 0 , 1 9 6 9 , 2615. M. Regitz, H. Scherer, and W. Anschiitz, Tetrahedron Letters, 1970, 753.

63

Phosphine Oxides 0 OMe I1 1 R,PCHR'

L) (40) 100%

0 II R,PC(N,)R'

(36)

0 I1 R,PCR1

+

N,

Ph

I

1 I

R'= COPh

PhP(0Me)CHCOPh

\

(37) 77%

R,PCHR1

I

(38)

30%

C6H9

+ 0

Similar carbenes are also produced by the thermolysis 39 of the phosphine oxides (41), and these are either trapped by aniline directly or undergo a Wolff rearrangement before reacting with aniline. A detailed kinetic and thermodynamic study of these reactions shows 39 that the initial and ratedetermining step is the cleavage of nitrogen to form the carbene (42). In the acid-catalysed hydrolysis 40 of the same oxides, (41), the rate-determining step is protonation of (41), followed by a fast loss of nitrogen and formation of a-hydroxybenzyldiphenylphosphine oxides (43). The first successful synthesis of a phosphepine has been reported.41 The key steps in this synthesis involve the photochemical cycloaddition of 1-phenylphosphol-3-en-1-oxide(44) to the imide (45) to produce (46), which was converted to the phospholan-1-oxide (47), and thermal ringopening of (47) to give a carbon skeleton, readily transformed to 1-phenylphosphepine-1-oxide (48). Treatment of allylic phosphorus compounds with basic alumina results The alkylin their conversion to propenyl compounds, e.g. (49) to (44) by successive reactions, with ation of 1-phenylphosphol-3-en-1-oxide butyl-lithium and benzyl bromide, results in the formation of (51).43 39 40

41 42 43

W. Jugelt and D. Schmidt, Tetrahedron, 1969, 25, 5569. W. Jugelt and K. Drahn, Tetrahedron, 1969, 25, 5 5 8 5 . G. Mark1 and H. Schubert, Tetrahedron Letters, 1970, 1273. L. Horner, I. Ertel, H.-D. Ruprecht, and 0. Belovsky, Chem. Ber., 1970, 103, 1582. F. Mathey and J. P. Lampin, Compt. rend., 1970, 270, C, 1531.

Organophosphorus Chemistry

64 0

PhzP ‘I -C O

R

0

NHPh

+ H+11

0

Ph2P-CH

I

+N,

i i ii iii iv

H‘ (47)

H,SO, CH,N, Ni-H, Electrolysis

65

Phosphine Oxides 0

II

0 II

z

CH2= CHCH,PPh, ' ' 2 I *

CH,CH=CHPPh, (50) 93%

(49)

CH,Ph (44)

i BuLi ii PhCH,Br

'

Ph' (51)

Further examples of the conjugate addition of anions to l-alkynylphosphine oxides and sulphides have 46 Grignard reagents add to ~ ~ with lithium 1-alkynyl sulphides (52) to give vinyl ~ u l p h i d e s ,and aluminium hydride, the addition has been shown by n.m.r. to be trans.46 No desulphuration occurs in the latter reaction. S

II

RZMgX

XII RZP- C=CR1 (52)

/

R,PCH= CR1R2

(98%, R

\

= Ph,

R1= R2= Me)

s.II. R2 p,

/

/=c, R

=

H R1

Me, R1= Et)

The deoxygenation reactions of triphenylphosphine oxide-sodium hydride continue to be of use in the synthesis 46 of ferrocenyl olefins, such as (53), from ferrocenyl ketones. The r81e of the organophosphorus intermediates in these reactions. has not been investigated 0

II

(Et)Fc,

(Et) Fc C Ph

+ Ph,PONa

(Fc = Ferrocene) A

Ph ,

c=c,

Ph'

Fc(Et)

(53)

The major product of the electrochemical reduction of dibenzylphenylphosphine oxide is reported *' to be an unidentified cyclohexadienyl 44 *5 46

47

A. M. Aguiar and J. R. S. Irlan, J. Org. Chem., 1969,34,4030. A. M. Aguiar, J. R. S. Irlan, and N. S. Bhacca, J. Org. Chem., 1969,34,3349. H.Patin, Compt. rend., 1970,270, C, 243. L. Horner and H. Neumann, Chem. Ber., 1969,102,3953.

66

Organophosphorus Chemistry

dibenzylphosphine oxide. Diphenylphosphinylcarbodi-imides(54) result from the treatment of the corresponding thioureas with mercuric oxide, or with phosgene.4s

0

s

II

II

Ph,PNHCNHR

HgO

(or COCI,)

0 I1 Ph,PN==C=NR (54)

Displacement of fluoride ion from both the para- and ortho-positions of pentafluorophenyldiphenylphosphineoxide and sulphide (35, X = 0, and X = S respectively) by methylamine has been

D. Miscellaneous.-The electronic effects of phosphinyl groups have received detailed attention in the recent literature 49--51 and have been reviewed.62 In particular, the Hammett constants for the ionisation of diphenylphosphinyl benzoic acids 40 and toluic acids show that the diphenylphosphinyl group withdraws electrons by both inductive and resonance effects. X-Ray structures 64 of the 2,2,3,4,4-pentamethylphosphetan-1 -oxides ( 5 5 ; R = CP3 or Ph54) have been determined, and the stereochemical assignment of phosphetan compounds has been altered 55 as the result of an 63v

Me

..

(55)

(56)

X-ray structure determination, although this does not affect the validity of the stereochemical studies of these compounds (reported in Chapter 1). The heterocyclic rings of oxides ( 5 5 ) and of the oxide (56) are found 63*K4*66 to be puckered. Papers devoted to the and n.m.r.58s59spectra of phosphine oxides and sulphides have appeared. 48 W

L1

Kz 63 64

Ks s6

K7

s8

Kg

G. Tomaschewski, B. Breitfeld, and D. Zanke, Tetrahedron Letters, 1969, 3 191. E. N. Tsvetkov, D. I. Lobanov, L. A. Izosenkova, and M. I. Kabachnik, Zhur. obshchei Khim., 1969,39, 2177. E. N. Tsvetkov, R. A. Maievannaya, D. I. Lobanov, N. G. Osipenko, and M. I. Kabachnik, Zhur. obshchei Khim., 1969, 39, 2429. E. N. Tsvetkov, D. I. Lobanov, M. M. Makhamatkhanov, and M. I. Kabachnik, Tetrahedron, 1969, 25, 5623. T. A. Mastryukova and M. I. Kabachnik, Russ. Chem. Rev., 1969, 38, 795. Mazhar-ul-Haque,J . Chem. SOC.(B), 1970, 934. Mazhar-ul-Haque, J . Chem. SOC.(B), 1970, 938. S. E. Cremer, Chem. Comm., 1970, 616. Mazhar-ul-Haque,J . Chem. SOC.(B), 1970, 711. G. N. Chremos and R. A. Zingaro, J. Organometallic Chem., 1970, 22, 647. R. H. Kemp, W. A. Thomas, M. Gordon, and C. E. Griffin, J . Chem. SOC.(B), 1969, 527. C. E. Griffin and W. A. Thomas, J. Chem. SOC.(B), 1970, 477.

5 Tervalent Phosphorus Acids ~~

BY 6. J. WALKER

1 Introduction Since almost three hundred papers concerning tervalent phosphorus acids have appeared in the twelve months covered in this Chapter, the policy of selection adopted in the first Specialist Report in ‘Organophosphorus Chemistry’ has been continued. 2 Phosphorous Acid and its Derivatives A. Nucleophilic Reactions.-@ Attack on Saturated Carbon. Organosiliconsubstituted phosphites (1) have been shown to undergo normal Arbusov reactions with alkyl halides to give the phosphonates (2).l However, in a reaction where the halide has a choice of attack on silicon or carbon, the latter is observed to give phosphonate (3) and alkyl halide, rather than silicon halide. 4-Methyl-2,6,7-trioxa-l-phosphabicyclo[2,2,2]octane (4) 0 RIX ---+

R20P(OSiR,),

+ RIX

-

II

+ R3SiX

II

+ R2X

(R3Si0),P-R1 (2) 0 (R,SiO),P-R1 (3)

reacts with alkyl halides to give the expected Arbusov product in both cis ( 5 ) and trans (6) forms.*

A kinetic study of the reaction of o-(hydroxymethy1)phenol (7) with phosphite esters suggests that it takes place via the quasi-phosphonium

a

N. F. Orlov, M. A. Belokrinitskii, B. L. Kaufman, and E. V. Sudokova, Khim. Prakt. Primen. Kremniiorg. Soedin., Tr. Sovesch., 1966 (Pub. 1968), 117 (Chem. Abs., 1970, 72, 90,571). R. S. Edmundson and E. W. Mitchell, J. Chem. SOC.(C), 1970, 752. B. E. Ivanov, A. B. Ageeva, A. G. Abul’Khanov, and T. A. Zyablikova, Zzvest. Akad. Nauk. S.S.S.R., Ser. khim., 1969, 1912 (Chem. Abs., 1970, 72, 21,110).

68

Organophosphorus Chemistry

I 332

o F p 4 o ' 0 ' O R

,o t

00:6R)2

(10)

(9)

salt (8). The rate-determining step appears to be *decomposition of this salt (8) by an Arbusov-like reaction involving attack of hydroxide on an alkoxy-group to give the phosphonate (9), which finally cyclises to (10). The reaction of tervalent phosphorus compounds with epichlorohydrin (1 1) can take place by halide displacement, or epoxide ring-opening. Both phosphite and phosphonite esters largely follow the latter pathway to give ally1 chloride as the main product, presumably via the betaines (12). 0

RIP(OR),

/ \ -I- H2C-CH-CH2Cl

---+

(OR), R'P-CH,

RI

= alkyl

t , L l

0 -CH - CH2CI

(1 1)

or alkoxy

(12)

II R1P(OR)2

+

CHZ = CH-CHZCI

Corey, in his study of phosphonate olefin synthesis, has reacted cis- and trans-but-2-ene oxides with the phosphite-derived anion (13).6 Attack appears to be entirely at phosphorus, with no products derived from nucleophilic oxygen, and stereospecific in each case to give the isomeric /3-hydroxyphosphoramides (14) and (15). Decomposition of these intermediates in the presence of base takes place via a cis-elimination to give 96% cis-but-2-ene from (14) and 99% trans-but-2-ene from (15). (ii) Attack on Unsaturated Carbon. The addition of tervalent phosphorus esters to olefins activated by electron-withdrawing substituents is well V. S. Abramov and R. N. Savintseva, Zhur. obshchei Khim., 1969,39,849 (Chem. Abs., 1969,71,61,482). V. S. Abramov and R. N. Savintseva, Zhur. obshchei Khim., 1969, 39, 1967 (Chem. Abs., 1970,72, 31,940). E. J. Corey and D. E. Cane, J . Org. Chem., 1969,34, 3053.

69

Tervalent Phosphorus Acids

known.’ Dialkyl phosphites cause cyclisation of vinyl ethers of the type (16) to give phosphonates (17) of which more than 90% are cis. The mechanism of this reaction is obscure and the fact that similar additions have been shown to be free-radical in nature provides no explanation of 0 II

H2C=HC I

CH=CH, \

O Y R O

+

0 H,CHCH2 I/ (R0)2PH +

P(0R12

O Y O

R

(16) (17) its stereospecificity. Tri- (18) and tetra- (19) phosphonic esters have been

prepared from the reaction of dialkyl phosphites with hydroxyacetylenes. Since this reaction requires the presence of base it seems unlikely that it involves free-radicals, and a series of additions and dehydrations seems more acceptable.1°

’ ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The

lo

Chemical Society, London, 1970, Vol. 1, p. 81. B. A. Trofimov, A. S. Atavin, G. M. Gavrilova, and G. A. Kalabin, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1200 (Chem. Abs., 1969, 71, 50,117). Chem. Abs., 1969,71, 50,212. W. A. Cilley, D. A. Nicholson, and D. Campbell, J. Amer. Chem. SOC.,1970,92, 1685.

70

-

0

II HCEC.CH2OH -I- 3(RO),PH

Na

Organophosphorus Chemistry 0

0

II II (RO),PCH2-CH-CH2P(OR)2 / (RO) P=0 (18)

0 0 (RO),P=O 0 11 Na I1 / I1 4(RO)2PH + (RO)zPCH,CH - CH-CH,P(OR), / (RO),P=O

+

HOCH2.C EC*CH20H

(19)

Irradiation of mixtures of dialkyl phosphites and 1,2-dichloro-3,3,4,4tetrafluorocyclobutene leads to the formation of the vinyl phosphonates (20) rather than the expected saturated compounds (21).11 In spite of the required irradiation, the mechanism may involve an ionic additionelimination.l2

F

'jT[ +

F F

. CI

F

CI

:$T[?

(RO),P<'

c1

H

F

P(OR)2

F

C1

$ F --@!j

0NP(OR),

(20)

(21)

Diethyl phosphite anion adds to N-methylacridinium salts (22) to give the phosphonate (23), which shows normal phosphonate behaviour except

&

+ (EtO),P-O 1

+

-

Na+

(22)

(23)

&

1

RMgBr

Me

1


/

\

Et

HO'

P=O 'OEt

(25)

in its reaction with Grignard reagents.13 These catalyse a rearrangement to the half ester (25), presumably by the Grignard reagent acting as a base l1 l2

l3

T. Ueda, K. Inukai, and H. Muramatsu, Bull. Chem. SOC.Japan, 1969,42, 1684. See ref. 7, Vol. 1, p. 81. D. Redmore, J . Org. Chem., 1969,34, 1420.

Tervalent Phosphorus Acids 71 to give the phosphonate anion (24). However, the co-ordinating properties of magnesium are probably important since (24) does not rearrange when generated from (23) with butyl-lithium. Triethyl phosphite catalyses the formation of stilbenol (26) from the quinone methide (27).14 The dis-

fy+ -y-J - yy (EtO),P

CH2P(OEt),

CH2

C H =P(OEt 1, (28)

(27)

?-

OH

CH

II

OH

+

(EtO),P

f--

CH2 I + CH-P(OEt),

A OH

(26)

appearance of (27) follows second-order kinetics [first in (27) and first in phosphite] and stilbenol is not a product from the condensation of (27) in the absence of phosphite. A multistep mechanism is proposed involving initial addition of phosphite to methide carbon, evidence for the intermediacy of the ylide (28) being obtained by trapping with benzaldehyde. A number of papers have appeared dealing with the addition of secondary phosphites to Schiff’s bases l6 and the reaction has been applied to the synthesis of a-aminophosphonic acids (29).16 Russian workers have shown that Mannich reactions of secondary phosphites probably proceed by similar additions to intermediate Schiff’s bases (30) since a-hydroxyphosphonates (31) and primary amines do not react under these condition~.~’ 14 l6

18

l7

W. H. Starnesjun., J. A. Meyers, and J. J. Lauff, J . Org. Chem., 1969, 34, 3404. e.g. A. N. Pudovik, L. V. Spirina, M. A. Pudovik, Yu. M. Kargin, and L. S. Andreeva, Zhur. obshchei Khim.,1969,39, 1715 (Chem. Abs., 1969,71, 124,597); B. P. Lugovkin, Khim. geterotsikl. Soedinenii, 1969, 694 (Chem. Abs., 1970, 72, 67,051). R. Tyka, Tetrahedron Letters, 1970, 677. N. S. Kozlov, V. D. Pak, and E. S. Elin, Zhur. obshchei Khim., 1969, 39, 2407 (Chem. Abs., 1970, 72, 79,156).

Organophosphorus Chemistry

72 (~iO),p<~

H

+

0 II H (R10)2P-CH--N-CH2Ph i R2

--+

R2CH=N--CH2Ph

i , OHii, H,-Pd

0 11

(HO),P-CH-R2 1

N H2

(29) RlCHO

+

R2NH,

__f

R1CH=NR2

(30)

0 R1 II I (R30),P-CH-0H

5- R2NH2

0 II H (R30),P-CH--N-R2

1

(3 1)

R1

The addition of tervalent phosphorus to Mannich phenol bases l8 remains p0pu1ar.l~ The Mannich base (32) undergoes two simultaneous first-order reactions with triethyl phosphite to give pent-3-en-2-one (33) and the phosphonate (34).20

1

WO)$

0 0 II II (EtO), P -CH-CH2-C -OMe 1 Me (34) l8

See ref. 7, Vol. 1, p. 82.

l9

e.g. S. G. Salikov, E. I. Loginova, B. E. Ivanov, A. Ageeva, S. V. Pasmanyuk, and

2o

R. R. Shagidullin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1757 (Chem. Abs., 1970, 72, 3531); W. E. Hahn and J. Weglewski, Lodz. Tow. Nauk Wydz. III, Act0 Chim., 1968, 13, 49 (Chem. Abs., 1969, 71, 70,697). B. E. Ivanov and V. F. Zheltukhin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 828 (Chem. Abs., 1969, 71, 21,421).

73 Tris(dimethy1amino)phosphine (35) will convert esters containing an

Terualent Phosphorus Acids

electron-withdrawing a-substituent into the corresponding NN-dimethylamides.,l A closely related reaction has been used to prepare fluorodiphenylphosphine (37) from the aminophosphine (36) and benzoyl 2RCH2.C02Et + (Me,N),P (3 5 ) R = CN, C02Et, OH, etc.

-

2RCH2CO-NMe2+ Me,NP(OEt),

fluoride.22 The alternative route from chlorodiphenylphosphine and Ph,PNHPr (36)

+ PhCOF

Ph2PF + PhCO-NHPr (37) Ph2PF8 PhZP.PPh2

+

3PhzPF

(38)

sodium fluoride gives a mixture of products, due to disproportionation of the flu orodiphenylphosphine to t rifluorodiphenylphosphorane (3 8) and tetraphenyldiphosphine under the conditions required for reaction. Alkyl benzoates react with chlorodiphenylphosphine (39) at elevated temperaPhCOzR

+

PhZPC1

-

PhCOO-

+

c1

RPPh2 -I-

(39)

0 PhCOCl

+

II RPPh2 (40)

-

/5(+ PhCOO PPha

+IR

Cl-

tures to give benzoyl chloride, alkyldiphenylphosphine oxide (40), and alkyl chloride.23 It is suggested that the products are derived from two separate reaction pathways. The first involves initial attack of phosphine on the ester alkyl group and leads to benzoyl chloride and phosphine oxide (40). The second involves initial attack of phosphine at the carbonyl carbon, followed by an Arbusov reaction to give the alkyl halide and benzoyldiphenylphosphine oxide (41). An alternative would appear to be that all the products arise via the intermediate (42); the phosphinite (43) would readily rearrange under the reaction conditions. Chlorodialkoxyphosphines react with acid anhydrides to give acylphosphonates (44),24 although the phosphine oxide analogues (45) of these compounds are not known.,,, 25 a1 23

23 24

25

R. Burgada, Compt. rend., 1969, 268, C, 1310. C. Brown, M. Murray, and R. Schmutzler, J. Chem. SOC.(C), 1970, 878. S. T. McNeilly and J. A. Miller, Chem. Comm., 1969, 620. M. B. Gazizov and A. I. Razumov, Zhur. obshchei Khim., 1969,39, 2600. K. Issleib and E. Priebe, Chem. Ber., 1959, 92, 3183.

Organophosphorus Chemistry

74 Ph-CO,R+Ph,PCI

PhC0.;Ph2

-OR

Cl I

0

II

PhCOPPh, + RC1

+---

+

PhCO -PPh,

Cl-

I

(41)

OR

(42)

PhCOCl 3- ROPPh2 (43)

RPPhz

II

0

The addition of dialkyl phosphite anions to carbonyl groups has been used to prepare carbohydrate C-phosphonates. The addition takes place to give a major amount of (46) and a minor amount of (47).26 A recent 0

It

R2P-CO- R (45)

patent describes the reaction of dimethyl phosphite with methylketen (48) to give derivatives of the antibiotic phosphonomycin (49), presumably by initial attack of phosphorus at the carbonyl carbon of (48). The same product is obtained from the reaction of trimethyl phosphite with a-cyanopropionaldehyde (50),28which presumably exists largely in the enol form (51). Ramirez has continued his work on the addition of tervalent phosphorus to carbonyl compounds (see also Chapter 2) and has shown that 26 27

28

L. Evelyn, L. D. Hall, P. R. Steiner, and D. H. Stokes, Chem. Comm., 1969, 576. Chem. Abs., 1970, 72,90,621. Chem. Abs., 1970, 72,90,622.

Terualent Phosphorus Acids Me

75 Me

Me

Me

oxo

oxo

u

Me

0 II (MeO),PH

+

CH,CH=C = O (48)

T

/

CN (MeO),P

+

N

i

0

II /O\ (MeO),P -HC -CH -CH, (49)

CH, -CH-CHO (50)

CN 1 CH,C=CH-

OH

(51)

trimethyl phosphite reacts with perfluorobenzaldehyde at 0 "C to give both cis- and trans-forms of the phosphorane (52), while at 80 "C the same reactants give the pentaoxyphosphorane (53).29 The product formed depends on the site of initial attack, at carbonyl carbon to give (52) and at carbonyl oxygen to give (53). Attack at oxygen is assisted by electronwithdrawing substituents on the carbonyl group.go 2s

yo

F. Ramirez, J. F. Pilot, C. P. Smith, S. B. Bhatia, and A. S. Gulati, J . Urg. Chem., 1969,34, 3385. F. Ramirez, Accounts Chenz. Res., 1968, 1 , 168; F. Ramirez, S. A. Gulati, and C. P. Smith, J . Org. Chem., 1968, 33, 13.

Organophosphorus Chemistry

76

0-

F

\

F

OMe MeO... I

Meo'i&r H Ar

(53)

Orthoformate esters 31 and their derivatives 32 react with tervalent phosphorus compounds, secondary phosphine oxides giving a-aminophosphine oxides with (54) 32 presumably via attack of phosphorus on (55). 0

II

Me,N - CH,.(OMe)2

R,PH

+

+

[Me,N-CH=O-Me]

+

(55)

(54)

RZP-0 U

-

MezN-CH- OMe I RzP=O

Y = CHZ, 0, RN 31 32

H. Gross and B. Costisella, J. prakt. Chem., 1969, 311, 571. H. Gross, B. Costisella, and L. Haase, J. prakt. Chem., 1969, 311, 577; H. Gross and B. Costisella, J. prakt. Chem., 1969, 311, 925.

Teruatent Phosphorus Acids 77 Numerous papers have appeared dealing with the reactions of tervalent phosphorus compounds with conjugated dienes and their hetero-analogues (56) 33 (the reactions of a-diketones and phosphite esters are reviewed in Chapter 2). It has been found that the rate of addition of (57) to (56) increases with increasing electron-acceptor character of X and so a transition state (58) has been suggested, but presumably this only applies when the diene is not ~ymmetrical.~~ Trimethyl phosphite reacts with l-phenyl-3methyl-4-benzylidene-5-pyrazolone (59) to give a mixture of N-methylated (60) and 0-methylated (61) products, presumably by initial attack at benzyl carbon followed by an inter- or intra-molecular Arbusov reaction.36

PhHC (MeO),P

(M eO>3PiI

(M eO)

I

+ -0

Ph

Ph (59)

0

0

PhHC

PhHC

I

Ph

Ph (60)

N' Ph

(61)

Tervalent phosphorus compounds will displace nitro-groups from activated aromatic rings 'in certain cases.36 o-Dinitrobenzene gives the phosphonate (63) but p-dinitrobenzene and o-chloronitrobenzene only give products of deoxygenation (see Chapter lo), probably because the displacement reaction is unable to compete in rate. A reasonable mechanism involves an Arbusov reaction with nitrite ion (62) but this does not explain why only ethyl nitrite is obtained when the NO,- ion is known to show ambident character. An alternative is provided by a cyclic elimination from the pentavalent intermediate (64), the nitrite ion attacking phosphorus entirely through oxygen due to their high affinity. 33

34

36

e.g. L. S . Kovalev, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 869 (Chem. Abs., 1969, 71, 50,077). N. A. Razumova, Zh. L. Evtikova, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 1419 (Chem. Abs., 1969, 71, 80,443). B. A. Arbusov, E. N. Dianova, V. S. Vinogradova, and A. A. Musina, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1530 (Chem. Abs., 1969, 71, 113,052). J. I. G. Cadogan, D. J. Sears, and D. M. Smith, J. Chem. SOC.(C), 1969, 1314.

Organophosphorus Chemistry

I8

1

:P(OEt),

N=O (64)

R

Displacement of halide from 2-chloro-triazines by phosphite to give the phosphonate (65) has also been a~hieved.~' (iii) Attack on Oxygen. The concept of tervalent phosphorus attack on oxygen has become more acceptable over the past few years and it is now being postulated as the initial step in many reactions. The adduct (66) between ozone and triphenyl phosphite3* has been used in a variety of chemical oxygenations and it has been concluded that singlet oxygen is in~olved,~@ although the most recent work suggests that two separate mechanisms may operate simultaneously. The first involves decomposition of the adduct (66) to phosphate and singlet oxygen, while in the second, oxygen is transferred directly from the adduct to the interacting species. (PhO),P

+ O3

-78 o c ____f

(PhO),PO, (66)

-15 "C

(PhO),PO

+ 02

Diethyl peroxide reacts with phosphites to give oxyphosphoranes (67) but the product is always contaminated with some p h ~ s p h a t e .As ~ ~might be expected, in view of the release of strain involved in the formation of 87

38

40 41

R. M. Ismail, Annalen, 1970, 732, 107. Q. E. Thompson, J. Amer. Chem. SOC.,1961,83, 845. R. W. Murray and M. L. Kaplan, J . Amer. Chem. SOC.,1969,91,5358; E. Wassermann, M. L. Kaplan, R. W. Murray, and W. A. Yager, J. Amer. Chem. SOC.,1968,90,4160. P. D. Bartlett and G. D. Mendenhall, J . Amer. Chem. SOC.,1970, 92, 210. D. B. Denney and D. H. Jones, J. Amer. Chem. SOC.,1969,91, 5821.

Tervalent Phosphorus Acids 79 small rings containing pentavalent phosphorus, phosphites containing the phosphorus in a five-membered ring react much more readily than acyclic, or larger ring, examples. This has led to the suggestion that a transition state (68) is involved rather than direct displacement of ethoxide.

lH and n.m.r. studies on pentavalent phosphorus compounds obtained in this way have shown that their structure depends on the substituents in the original tervalent phosphorus When these contain at least one alkoxy-group, the products contain pentacovalent trigonal-bipyramidal phosphorus (69), but when phosphines are used the products appear to be in an equilibrium mixture with the ionic form (70). Acyclic aminophosphines and diethyl peroxide give only tetra-co-ordinate compounds (71), but the cyclic aminophosphine (72) does give a phosphorane (73), although a much less stable one than that obtained from the equivalent phosphite. Tervalent phosphorus halides react with t-butyl

(69)

PhP(NEt,),

+

EtOOEt

-

Me I

[>R

+

EtOOEt

_I+

OEt

(73)

(CH,),C-O-OH

R2P-O-O-C(CH3)3 (75) 4p

(71)

"P,-R

(72)

+

ll

PhP(NEt,),

N, ,oEt

I Me

R,PCI

0

PY

~

0 '1 R2P-O-C(CH3)3 (74) 0 II RzPCl (76)

[D. B."enney, D. Z. Denney, B. C. Chang, a n d K. L. Marsi, J. Amer. Chern. SOC., 1969,91, 5243.

80 Organophosphorus Chemistry hydroperoxide to give phosphoryl derivatives (74).43 Formation of the peroxy-compound (75) followed by rearrangement is excluded as the mechanism and the reaction is thought to take place via the phosphoryl chloride (76). A number of papers have appeared describing the reactions of cyclopentadienones with phosphite esters. In non-aqueous solvents tetracyclone reacts with trimethyl phosphite to give phosphates (77) and (78) together with some 1,2,3,4-tetraphenylfulvalene (79).44 It is suggested that the initial attack of phosphite is on carbonyl oxygen to give (80), by analogy with previous inter- or intra-molecular Arbusov reactions then lead to (77) and (78). The fulvalene is thought to be formed via the other possible phosphate (81).

'6".

Ph

Ph

+ Ph Ph Ph QPh

Other workers 46 claim that tetracyclone and trimethyl phosphite give the phosphate (82), rather than (77) and (78). However, it has been suggested44 that this product may arise through reaction of the dimethyl phosphonate impurity commonly found in samples of trimethyl phosphite. In aqueous alcohol the reaction follows a quite different pathway to give 43 44

O5 O6

G. Sosnovsky, E. H. Zaret, and K. D. Schmitt, J. Org. Chem., 1970,35,336. M.J. Gallagher and I. D. Jenkins, J. Chem. SOC.( C ) , 1969, 2605. R. F. Stockel, Chem. Comm., 1968, 1594. S. Ranganathan and B. B. Singh, Chem. and Ind., 1969, 1093.

Tervalent Phosphorus Acids 81 mainly the phosphonate (83).*' The cyclopentadienylidene ylide (84) has been isolated as an intermediate in this reaction and a possible mechanism involves deoxygenation of the ketone by the route shown.

Ph

Ph

(83)

A closely related reaction appears to be that between triethyl phosphite and phthalic anhydride to give the deoxygenated dimer (85).48 A carbene dimerisation mechanism is disproved in this case since a major amount of the mixed product (86) is obtained from reactions of phosphite with a mixture of phthalic anhydride and its analogue (87). Since the sulphur compound is known to react very much more quickly with phosphites than phthalic anhydride, it seems unlikely that comparable concentrations of the two carbenes will be present simultaneously. A more reasonable mechanism involves a Wittig reaction between the intermediate ylide (88) [formed in an analogous way to (84)] and a further mole of anhydride. A similar reaction has been used to dimerise the ketone (89).49 Dialkyl phosphites react with tetracyclone in aqueous ethanol to give the cyclopentenone (90), and a mechanism involving initial attack on oxygen followed by proton transfer and hydrolysis has been ~uggested.~'The trans-stereochemistry of the product is deduced from the n.m.r. coupling constants. The reaction between diphenylphosphine oxide and tetracyclone

*' 48

dB

A. J. Floyd, K. C. Symes, G. I. Fray, G. E. Gymer, and A. W. Oppenheimer, Tetrahedrorz Letters, 1970, 1735. C. W. Bird and D. Y. Wong, Chem. Comm., 1969, 932. G. Mtirkl, D. E. Fischer, and H. Olbrich, Tetrahedron Letters, 1970, 645.

Organophosphorus Chemistry

a2

+

fyJ \

0

+ Ph (89)

Ph

0

0 (90)

has also been studied and the products depend on the pH of the solutions involved. In the presence of base the phosphine oxide (91) is the only product, but when the reaction is carried out in neutral, or acid, solution the major products are (92) and (93) with only a minor amount of (91). bo

J. A. Miller, Tetrahedron Letters, 1969, 4335.

83

Tervalent Phosphorus Acids

Reaction of triethyl phosphite with the dibromoketone (94) to give the phosphate (95)6a could be via initial attack on halogen or oxygen (cf. Perkow reaction 9. When the choice of attack is oxygen or nitrogen, as in (96), the phosphite only attacks oxygen to give the phosphate (97). It is interesting that the N-methylated product (98) is not formed in this reaction, but it has been found that the reaction will not take place at all unless water or some other proton source is present.

& \

\

Br

0 II

+

(MeO),P

4

Br

Br (95)

(94)

0

”$-, \

\

ii

0- P (OMe),

+

(MeO),P

--+ NHPh

NPh

(96)

0 II 0-P(OMe),

NMePh

61 6a

Diss. Abs. 1969, 29, B, 4117. J. S. Meek and L. Koh, J. Org. Chem., 1970, 35, 153.

(97)

84

Organophosphorus Chemistry

The reaction of trimethyl phosphite with ( -)-menthy1 pyruvate ester has been used in a partial asymmetric synthesis of 1,2-dimethyltartaric The initial product of the reaction is the oxyphosphorane (99) which can be hydrolysed with aqueous alkali to give partially resolved tartaric acid. The asymmetric induction is explained in terms of steric effects in the transition state for formation of the oxyphosphorane (99). (Me0)3P

+

+ o

--+

(MeO),P'

O/ O X C0-Men H3

Ho-C
I

I

CH3

-

CH3

l'C-CO-OMen

-OH

P-C-

,CH, CO-OMen

( M e 0 ) 3 p \ 0 ~ A ~co -*Men CH3 (99)

Tris(diethy1amino)phosphine has been used to convert the tetrasulphide (100) into its d i ~ u l p h i d e presumably ,~~ by initial attack at sulphur. The reaction of trialkyl phosphites with (101) to give symmetrical tetra-alkyl

ClW

monothiopyrophosphates has been interpreted in terms of initial attack at sulphur followed by an Arbusov reaction,56although a mechanism involving initial attack at halogen can be written. 0 (RO),P

II

+ (RO),P-S-Cl (101)

63

55

-

0

0

II

II

(RO),P-S-P(OR),

M. Muroi, Y . Inouye, and M. Ohn, Bull. Chem. SOC.Japan, 1969, 42, 2948. V. Boekelheide and J. L. Mondt, Tetrahedron Letters, 1970, 1203. J. Michalski and A. Skrowrbnska, J . Chem. SOC.(C), 1970, 703.

Terualent Phosphorus Acids 85 (iv) Attack on Halogen. The Perkow reaction has been reviewed.51The reaction of trialkyl phosphites with 1 ,1 ,Ztrihalogenopropionitrile(1 02) provides The suggested mechanism a new synthesis of /3-halogenoa~rylonitriles.~~ involves initial attack at an a-halogen and elimination, followed by an

X I (RO),P 3- X2CH-CH-CN

+

+

(R0)2P-X 1 1 (103)

(RO)zPC0

+

XCH=CHCN

RX

X Arbusov reaction, on the intermediate (103). Evidence for this was provided by reactions in ethanol, which gave phosphate and 1,2-dihalogenopropionitrile from hydrolysis of the initial products of attack at halogen. However, interpretations of this type must be treated with some caution since changes to hydroxylic solvents can lead to a complete change in reaction mechanism. Alkynylphosphonates (104) have been prepared in high yield from the reaction of phosphites with halogenoacetylenes containing a trimethylsilyl The initially formed silylated phosphonate forms (104) prote~ting-group.~~ on treatment with dilute sodium carbonate solution. (R0)3P

+ CI-CGC-SiMe3

0 ll

___f

(R0)2P-C~C-SiMe3

0

li

(R0)2P-CSC-H (104)

Tris(dimethy1amino)phosphine reacts with sulphur tetrafluoride to give a mixture of fluorophosphoranes (105) and (106) while a similar reaction with trimethyl phosphorotrithioite (107) gives tetra-co-ordinate products (108) and The monothiopyrophosphate (11 1) is formed together with a number of other products from the reaction of the phosphite (110) with thionyl 68 57 68

K. C. Pande and G . Trampe, J. Org. Chem., 1970, 35, 1169. D. W. Burt and P. Simpson, J . Chem. SOC.( C ) , 1969,2273. D. H. Brown, K. D. Crosbie, J. I. Darragh, D. S. Ross, and D. W. A. Sharp, J. Chem. SOC.( A ) , 1970,914.

4

86

Organophosphorus Chemistry

chloride. The three possible sites of attack (sulphur, halogen, and oxygen) are discussed, but no firm conclusions are drawn.6a (Me2N3 PF2

(Me2N 12 PF,

(105)

(106) S

S

II

li

SOCl,

Me

eJ(7s/;c"e 4+

Me

Me

0 H

0

(1 10)

(1 11)

(v) Attack on Hydrogen. The formation of the allenylphosphonate (1 12) from the reaction of dialkyl phosphites with 3-chloro-3-methylbut-1-yne 6o can be interpreted in terms of an SN2' displacement of halogen by attack of phosphite at acetylenic carbon. However, an alternative mechanism would appear to be proton abstraction to give the resonance-stabilised carbene (1 13) 61 which can insert into the phosphite P-H bond. 0

Me

\

It

___+

,Me

(RO),P-CH=C=C,

Me 0- PIOR),

(1 12)

f Me, Me

/c= c=c: (1 13)

B. Electrophilic Reactions.-Russian workers claim that acetyl phosphites (1 14) are better reagents than phosphorochloridites (1 15) for preparing 68 8o

A. Zwierzak, Tetrahedron, 1969,25, 5177. A. N. Pudovik and N. G. Khusainova, Zhur. obshchei Khim., 1969, 39, 1646 (Chem. Abs., 1969, 71, 91,591). G. F. Hennion and K. W. Nelson, J. Amer. Chem. SOC.,1957,79,2142; H. D. Hartzler, J. Amer. Chem. SOC.,1959, 81, 2024; G. F. Hennion and G. V. DiGiovanna, J. Org. Chem., 1965, 30, 3696.

Tervalent Phosphorus Acids

87

-

diphosphites from diols.s2 The stereochemistry of the formation of dibromides from bromohydrins using phosphorus tribromide has been (RO),POCOCH,

+ HO(CH2),0H

(RO),PO(CH,),OP(OR),

(114) The bromohydrin (1 16) reacts with phosphorus tribromide to give the dibromide with a largely retained configuration, while bromination with thionyl bromide causes almost complete racemisation, possibly because of an intermediate bromonium ion. In phosphorus tribromide brominations of cyclic bromohydrins considerable amounts of monobromides are often obtained.64 trans-Cyclohexene bromohydrin (1 17) reacts with phosphorus tribromide to give approximately equal amounts of dibromide and mono(RO), PC1

Et-&IBr-CH,OH

(116)

(1 15)

bromide (118). The fact that acyclic bromohydrins react much more slowly, and cis-cyclohexene bromohydrin gives only dibromide, suggests that some type of anchimeric assistance is involved. Evidence that the reaction involves the intermediate formation of cyclohexene followed by addition of hydrogen bromide is provided by the isolation of some cyclohexene from reaction mixtures to which 4-t-butylcyclohexene had been added prior to reaction. t-Butyldichlorophosphine has been prepared and its reactions interpreted in terms of the steric effects of the t-butyl group.65 Malonate diesters and dichlorophosphines react in the presence of triethylamine to give the novel cyclic ylides (1 19) 66 which are useful as additives in the RIPCI, 3- CHz(COOR)2

COOR COOR

Et,N

RO’ ‘R’

E8 64

I. V. Fursenko, G. T. Bakhvalov, and E. E. Nifant’ev, Zhur. obshchei Khim., 1968, 38, 2528 (Chem. Abs., 1969, 71, 21,790). G. Bellucci, F. Marioni, and A. Marsili, Tetrahedron, 1969, 25, 4167. G. Bellucci, F. Marioni, A. Marsili, P. L. Barili, and G. Berti, Chem. Comm., 1969, 1017. P. C. Crofts and D. M. Parker, J. Chem. SOC.( C ) , 1970, 332. Chem. Abs., 1970,72, 3566.

Organophosphorus Chemistry oxo-pro~ess.~~ The reaction presumably takes place by initial attack of malonate anion on the chlorophosphine. 2-Dimethylamino-l,3,2-dioxaphospholans(120) react with /3-aminoalcohols to give the spirophosphoranes (121), presumably via the phosphite (122)and cyclisation, since in certain cases these compounds appear to be in tautomeric equilibrium.6s 88

R[0)NMe2

+

R1 0

HO*CH2*CR2*NH2 \

(1 22)

C. Rearrangements.-Phosphites form adducts with dichloroethylalane which readily rearrange to give phosphonate complexes (123)? The wellknown rearrangement of phosphites to phosphonates has also been Me

I

Et

I

(MeO),P=O * AICla (123)

A number of papers dealing with acetylene-allene rearrangements have 72 In one of these 72 the optically active acetylenic alcohol (124)reacted with a chlorophosphine to give the allene (125) with

(125) 67 6*

'O

'I1

Chem. Abs., 1970, 72,43,856. M.Sanchez, L. Beslier, and R. Wolf, Bull. SOC.chim. France, 1969, 2778. B. M. Cohen and J. D. Smith, J . Chem. SOC.(A), 1969,2087. A. N. Pudovik and V. K. Krupnov, Zhur. obshchei Khim., 1969,39,2415 (Chem. Abs., 1970, 72,78,315). V. M. Ignat'ev, T. N. Timofeeva, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 2439 (Chem. Abs., 1970, 72, 79,159); ibid., p. 2446 (Chem. Abs., 1970, 72, 79,168); Yu. A. Kondrat'ev, E. S. Vdovina, Ya. S. Arbisman, V. V. Tarasov, 0. G. Strukov, S. S. Dubov, and S. 2. Ivin, ibid., 1968,38,2589 (Chem. Abs., 1969,71,22,153). A. Sevin and W. Chodkiewicz, Bull. SOC.chim. France, 1969,4016.

89

Tervalent Phosphorus Acids

retention of configuration, suggesting that the mechanism is of an S,i type. A similar type of mechanism appears likely for the rearrangement of the phosphite (126) in ethanol to give the phosphonate (127) via a keten intermediate.?, Care is required in interpreting the results from reactions of dialkyl phosphites with carbonyl compounds in terms of initial attack at carbon or oxygen. Changes in product with temperature can be due to change in site of initial attack 29 or to rearrangement of first-formed p r o d ~ c t75. ~The ~~ a-hydroxyphosphine oxides (128) formed from secondary phosphine oxides and chloral rearrange at 160 "C to give the vinyl phosphinates (129).7s 0 OH

II I

-

0

-

R2P CH CCI, (128)

-

--

160 "c

II

R2P.0 * CH :CC12 (129)

D. Cyclic Esters of Phosphorous Acid.-The n.m.r. spectrum of 2,7,8trioxa-l-phosphabicyclo[3,2,1]octane has been analysed and interpreted in terms of the bridged chair conformation (130).76 A variety of cyclic phosphites (131) have been prepared as mixtures of cis- and transisomers.77 In the phosphites, distinction between the geometrical isomers is possible by chemical shift differences of the alkyl group R1 in the lH n.m.r. spectra, since the alkoxy-group on phosphorus deshields cis-substituents. However, this distinction is not possible in the equivalent phosphates (which can be prepared stereospecifically from the phosphites by oxidation with nitric oxide), presumably because an oxygen atom lies on both sides of the ring. A similar distinction between phosphites and 73

74

75

70 77

T. Kh. Gazizov, A. P. Pashinkin, and A. N. Pudovik, Zhur. obshchei Khim., 1970, 40, 31 (Chem. Abs., 1970, 72, 100,826). A. N. Pudovik, I. V. Gur'yanov, M. G. Zimin, and 0. E. Raevskaya, Zhur. obshchei Khim., 1969, 39, 1021 (Chem. Abs., 1969, 71, 61,476); ibid., p . 1018 (Chem. Abs., 1969, 71, 61,477); A. N. Pudovik, I. V. Gur'yanov, and G. V. Romanov, ibid.,p. 2418 (Chem. Abs., 1970, 72, 79,164). V. S. Abramov, N. I. D'yakonova, and U. D. Efimova, Zhur. obshchei Khim., 1969,39, 1971 (Chem. Abs., 1970, 72, 31,938). M. Kainosho and A. Nakamura, Tetrahedron, 1969, 25, 4071. D. Z. Denney, G. Y. Chen, and D. B. Denney, J . Amer. Chem. SOC.,1969, 91. 6838.

Organophosphorus Chemistry

90

phosphates appears in isomer ratios. While one geometrical isomer predominates in the phosphite case, the equivalent phosphates are more nearly equal in stability.

(1 31)

(1 30)

The six-membered cyclic phosphite (1 33) has been prepared by ethanolysis of 4-methyl-2-chloro- 1,3,2-dioxaphosphorinane(132) and shown to exist as a mixture of geometrical isomers. The most stable of these is probably the trans with the conformation (134), while the cis has the conformation (135).78 The unexpected stability of the trans-isomer may be due to an anomeric effect. Confirmation of these results was obtained from dipole moment studies on the equivalent sulphides. The chloride (132), which was earlier shown to exist as one pure isomer,79 probably has the stereo(1 32) has chemistry (136).78 4-Methyl-2-chloro-l,3,2-dioxaphosphorinane also been hydrolysed in water-triethylamine to give a mixture of cis (137) and trans (138) secondary phosphites.80 Since this hydrolysis should take place with inversion at p h o ~ p h o r u s ,presumably ~~ an equilibration to the more stable cis-isomer (1 37) takes place after reaction. Me Me EtOH _____,

0

(138) hnns 78

78

C. Bodkin and P. Simpson, Chem. Comm., 1969, 829. G. Aksnes, R. Erikson, and K. Melligen, Acta chem. Scund., 1967, 21, 1028. M. Mikolajczyk, Chem. Comm., 1969, 1221.

91

Tervalent Phosphorus Acids

The cyclic phosphite (139) has been separated into its geometrical isomers and each of these reacted with neopentyl hypochlorite to give the phosphate (140).81 Stereospecific oxidation of the phosphite (141) also

-U

MeL"

<:+cH2CMe Me (141)

gave the phosphate (140) and if it is assumed that the more stable isomers of (139) and (141) have the same geometrical configuration, the stereochemistry of interconversion between (139) and (140) can be determined. Only one isomer of (139) undergoes stereospecific conversion to (140), and the results are explained in terms of two trigonal-bipyramidal intermediates (142) and (143), one of which is more stable, and which can interconvert by pseudoro t ation.

c):

products

bMe

Me

\

products

E. Miscellaneous Reactions.-Triethyl phosphite has been irradiated with y-rays and gives a mixture of products including diethyl phosphite and triethyl phosphate.82 The reaction between dialkyl phosphites and sodium has been reinvestigated 83 and found to follow the widely accepted route, to the anion (144) 8a

J. H. Finley and D. B. Denney, J. Amer. Chem. SOC.,1970,92, 362. K. Terauchi, Y. Aoki, and H. Sakurai, Tetrahedron Letters, 1969, 5073. G . M. Kosolapoff and A. D. Brown, Chem. Cumm., 1969, 1266.

92

Organophosphorus Chemistry

and hydrogen, only at high temperatures. If the reaction is carried out at less than 0 "C considerable amounts of phosphine (PH,) are produced. The first examples of an acyclic aminophosphine which exists predominantly in the imido-form (145) have been prepared and shown to require the presence of electron-donating substituents on phosphorus and electron-accepting ones on imido-nitr~gen.~~

-

(RO),P -0

-

Na'

(144)

3 Phosphonous Acid and its Derivatives Menthyl methylphosphinate (146) has been obtained 8 5 optically pure, [a18- 96.6" (benzene), and converted into (147) by two separate routes, both of which follow the same stereochemical course and give a product of Me,Me

0

II

R=

RO-P-H I Me

\ 0

Q" Me

MeSNEt,

OH +I

II

RO- P- SMe

RO-P-SI

I Me

Me

\ o

II RO- P- SMe

I

Me (147) 84 86

A. Schmidpeter and H. Rossknecht, Angew. Chem. Internat. Edn., 1969, 8, 614. H. P. Benschop, D. H. J. M. Platenburg, F. H. Meppelder, and H. L. Boter, Chem. Comm., 1970, 33.

Terualent Phosphorus Acids

93

similar optical purity. The epimers of (146) have a chemical shift difference of 4.3 p.p.m. in the 31Pn.m.r.86 4 Phosphinous Acid and its Derivatives /3-Naphthylphenylphosphineoxide (148) constitutes the second example of an optically active secondary phosphine The rate of nucleophilic substitution in phosphinite esters is greatly enhanced by the presence of transition-metal salts (FeCl,, CoCl,, NiC1,).88 Substitution with iodide ion will not normally take place at all at room temperature, but in the presence of salts, gives 1&60% iodophosphine after an hour, depending on the salt used.

(148) [cY];~"

- 0*59"(CHCIJ

F. H. Meppelder, H. P. Benschop, and G. W. Kraay, Chem. Comm., 1970,431. 0. Cervinka, 0. BElovskjr, and M. Hepnerva, Chem. Comm., 1970,562. R. Engel, T. Santo, D. Liotta, and D. Freed, Chem. Comm., 1970, 646.

6 Quinquevalent Phosphorus Acids BY N. K. HAMER

1 Phosphoric Acid and its Derivatives A. Synthetic Methods.-Up to the present time, successful phosphorylation procedures for alcohols have depended on activation of the phosphoryl group, since reactions involving nucleophilic attack by a phosphate anion on alkyl groups have hitherto shown little promise of general utility. Recently, a method which probably involves nucleophilic attack on alkoxy phosphonium salt intermediates shows promise for phosphorylation of primary alcohols. It utilises the reaction of triphenylphosphine with diethyl azodicarboxylate to give the probable intermediate (l), which with ROH and a mono- or di-ester of phosphoric acid is converted first to (2) H+ f-+

EtO-C-N=N-CO,Et

Ilf

H+

+

EtO,

/-

C=N-NHC0,Et

Ph,P:

Ph3P0

-

+ (R20)2P(0)OR1 (RzO)?P02- Ph,POR1 i-

and thence to the pr0duct.l An advantage of this approach is that nucleoside 2’- (or 3’-)positions do not require protection, and there are no pyrophosphate byproducts, as is common in more usual procedures. Selective phosphorylation of the 5’-hydroxy-group in unprotected nucleosides has been achieved with pyrophosphoryl chloride in phenolic solvents or phosphoryl chloride in a trialkyl phosphate3 solvent. It is probable that the solvents function in these reactions as weak bases possessing a large steric requirement. In contrast, unprotected ribonucleosides (and presumably many cis-vicinal diols) are converted by sodium tri2

0. Mitsunobu, K. Katu, and J. Kimura, J. Amer. Chem. SOC.,1969, 91, 6510. K. Imai, K. Takanohashi, Y. Furukawa, T. Masudo, and M. Honjo, J . Org. Chem., 1969,34, 1547. M. Yoshikawa, T. Kato, and T. Takenishi, Bull. Chem. SOC.Japan, 1969, 42, 3505.

Quinquevalent Phosphorus Acids

95

metaphosphate in aqueous sodium hydroxide4 to a mixture of the 2’- and 3’-phosphates, while the 5’- position and 2’-deoxynucleosides are relatively unaffected by these conditions. The isomer composition is similar to that obtained by hydroxide opening of the 2‘,3’-cyclic phosphates, implicating these as probable intermediates. Inorganic phosphate can be condensed with D-ribose in aqueous solution with either cyanogen or cyanamide and gives #bribofuranosyl 1-phosphate exclusively. Oxidative phosphorylation has been reviewed,s and the formation of ATP from ADP during the oxidation of the quinol monoacetate (3) with bromine in the presence of inorganic phosphate has been reported.’ The oxidation of monophosphite esters (4) of nucleosides to cyclic phosphates

GMe Br,

H3P04. ADP

’ATP

OH

(3)

ROH -t-2-0aP * S .CH,* CH,.CONH,

DCC ----+

0 II RO-P-S

I

O-

.CH,.CH, *CONH,

/OH-

RO * PO,Ss(5 )

with hexachloroacetone has been extended and used in the synthesis of nucleotides with unusual sugars.* 0-Alkyl phosphorothioates ( 5 ) may be prepared from the parent alcohol and tri(imidazoly1)phosphine sulphide, or more generally by the route shown.@Unlike the S-alkyl isomers, they give rise to disulphides rather than phosphorylating intermediates on oxidation with iodine. Phosphoenol pyruvate is also converted to a phosphorylating agent on oxidation with iodine in the presence of Ag+.l0

lo

A. W. Schwartz, Chem. Comm., 1969, 1393. M. Halmann, R. A. Sancher, and L. E. Orgel, J . Org. Chem., 1969, 34,4007. G. M. Blackburn and J. S. Cohen, Topics in Phosphorus Chem., 1969, 6, 187. T. Wieland and H. Aquila, Chem. Ber., 1969, 102, 2285. A. Holy, Coll. Czech. Chem. Comm., 1969, 34, 3510, 3523. A. F. Cook, J . Amer. Chem. SOC.,1970,92, 190. N. V. Volkova and A. A. Yasnikov, Ukrain. khim. Zhur., 1969, 35, 935.

96

Organophosphorus Chemistry

Further preparative studies on N-phosphorylated pyridines have been reported, and the 4-amino-derivatives (6; R = NH, or NHCHMe,) were iso1ated.ll 2-Aminopyridine was phosphorylated by phosphoryl chloride to a mixture of both (7a) and (7b). Bisdimethylamino(imidazoly1)phosphine oxide (8) has been prepared,12 and is broken down in both acid and base with loss of imidazole; in base, the principal hydrolysis product is NN'N"N"-octamethyl pyrophosphoramide. A convenient route to N-phosphoryl aziridines is provided by the reaction of a trialkyl phosphite with readily accessible #I-iodoalkyl azides l3 and probably involves the phosphorimidate (9) as an intermediate. CH,=C,

,CO2H

o.p0,2-

I,-Ag+

Upyrophosphates

R

The phosphorodichloridate (10) l4has been suggested as a useful reagent for the preparation of monoesters of phosphoric acid since it is converted in high yield to the diesters which, after quaternisation with pyridine, are hydrolysed extremely readily to the quaternary pyridinium salts of the products. Reaction of sodium peroxide with dialkylphosphorochloridates gives the unstable peroxydiphosphate esters (11) l5 which, however, contained only 40% of the theoretical active oxygen after isolation by distillation. *l

M. Wakselmann and E. Guibe-Jampel, Tetrahedron Letters, 1970, 1521.

12

Y.Le R o w , J. Bernadine, H. Grangette, and C . Nofre, Bull. SOC.chim. France, 1970,

l3

l4 l5

1459. A. Hassner and J. E. Galle, J. Amer. Chem. SOC.,1970,92,3733. T.Hata, Y. Mushika, and T. Mukaiyama, J. Amer. Chem. Soc., 1969,91,4532. V. I. Barabanov and T. A. Guseva, Zhur. obshchei Khim., 1969,39, 1176.

Quinquevalent Phosphorus Acids 97 The diethyl ester of t-butyl peroxyphosphoric acid (12) is much more stable but may be converted, in low yield, to the corresponding phosphate triester by deoxygenation with triphenylphosphine.ls

0 It

0

II

-

(RO), P 0 - 0 . P(OR

( 1 1)

The oxidation of di- and tri-esters with N2O4or sulphur to the corresponding phosphates or phosphorothioates is of well-established synthetic utility,17 and is often, as in the preparation of O-alkyl phosphorodiisocyanates,ls preferred to direct reaction with the appropriate phosphorochloridate. It appears to be stereospecific for cyclic esters, and evidence has been obtained to show that this stereospecificity is retained in reaction of an acyclic ester with sulphur,lD The reaction of neopentyl hypochlorite with the cyclic ester (13) is, however, not stereospecific,20a result attributed to the occurrence of pseudorotation in a pentacovalent intermediate. The symmetrical thiopyrophosphate esters (14) 21 have been obtained by reaction of dialkyl phosphites with NN-dialkyl chlorosulphenamides. Earlier methods were unsuccessful owing to the fact that phosphorothioate 18 17

G. Sosnovsky, E. H. Zaret, and K. D. Schmitt, J. Org. Chem., 1970,35, 336. J. R. Cox and F. H. Westheimer, J. Amer. Chem. SOC.,1958, 80, 5441; see also refs. 54, 108, 109.

18 19

V. A. Shokol, V. V. Doroshenko, N. K. Mikhailyuchenka, L. I. Molyavko, and G. I. Derkach, Zhur. obshchei Khim., 1969, 39, 1041. H. P. Benschop, D. J. M. Platenburg, F. H. Meppelder, and H. L. Boter, Chem. Cumm., 1970, 33.

20

21

J. H. Finley and D. B. Denney, J . Amer. Chem. Suc., 1970, 92, 362. 5. Michalski, M. Mikolajczyk, and B. Mlotkowska, Chem. Ber., 1969, 102, 90.

98

Organophosphorus Chemistry

I anions attack dialkyl phosphorochloridates with oxygen rather than sulphur, and that in addition the compounds undergo ready conversion to the thermodynamically more stable unsymmetrical esters (1 5). It appears that the symmetrical esters (14) may also be formed in the reaction of dialkyl phosphites with thionyl chloride 22 and in reaction of the sulphenyl , ~ ~ owing to the ease with which chloride (16) with trialkyl p h o s p h i t e ~ but they isomerise, they are not readily isolated from the reactions.

(16)

Aqueous sodium azide reacts with phosphorus pentasulphide to give the diazido dithioate ion (1 7a) and the related thiopyrophosphate derivative (17).24 N8

P*S,

-

S

S

(N3),PS2-

07a)

+

II II N3-P-S-P-N3 I I

s-

s-

(17) 22

2s 24

A. Zwierak, Tetrahedron, 1969, 25, 5177. J. Michalski and A. Skrowvonska, J. Chem. SOC.(C), 1970, 703. H. W. Kresky, U.S.P. 3,437,455.

Quinquevalent Phosphorus Acids

99

B. Solvolysis of Phosphoric Acid Derivatives.-A detailed study 25 of the hydrolysis rates and product distribution of methyl ethylene phosphate over the pH range - 1 to 15 has been reported. The fraction of exocyclic cleavage shows a remarkable dependence on pH, which has been elegantly interpreted in terms of the relative rates of interconversion: breakdown of the two pseudorotational conformers (18) and (19) in various states of ionisation (using reasonable estimates for the pK,'s of the OH groups). Making the usual assumptions that the ring preferentially occupies one apical and one basal position, and that entering and leaving groups2s occupy apical positions, the product distribution in the range pH 1-7 is satisfactorily accommodated on the basis that the acid-catalysed and neutral hydrolysis of the equilibrium mixture (18) and (19) proceeds with approximately 50 and 25% exocyclic cleavage respectively. In more strongly acid solution, the fraction of exocyclic cleavage falls, indicating that pseudorotation may here be rate-limiting. The negligible amount of exocyclic cleavage in the pH range 9-13 seems to require that the monoanion (18a) undergoes ring-opening faster than it pseudorotates to (19a) (since there is here no strong incentive to pseudorotate) whereas the increase in exocyclic cleavage at high pH values is reasonable on the assumption that there now exists a considerable driving force to bring both oxygens of the dianion (18b) to the energetically more favourable (19b), where both occupy basal positions.27

+

OMe (19)

C?..OH 0-P 1'0-

c

?-.OM e 0-P,

I

25

26

O-

Cq-00-P I '0-

R. Kluger, F. Covitz, E. A. Dennis, L. D. Williams, and F. H. Westheimer, J. Amer. Chem. Soc., 1969, 91, 6066. F.H. Westheimer, Accounts Chem. Res., 1968, 1, 70. D. S. Frank and D. A. Usher, J. Amer. Chem. SOC.,1967, 89, 6360.

1 00

Organophosphorus Chemistry

The hydrolysis of the dibenzyl ester of phosphoenol pyruvate (20), under conditions where it exists substantially as the neutral species, indicates a facile equilibrium with the corresponding acylphosphate.28 Although in water alone it gives the monobenzyl ester and benzyl alcohol (> 9573, in the presence of hydroxylamine to trap the acyl phosphate the hydroxamic acid and dibenzyl phosphate are formed almost exclusively. The interconversion of the starting material and the acyl phosphate is accommodated in terms of an allowed pseudorotation in the pentacovalent intermediate.

-

h

OCH,Ph .OH c-c 1-P; I OCH,Ph '

I

b

0 -0

OH

I

0

II

CH,=C-CO *O.P (OCH,Ph)2

Elo,OCH, Ph O-P-OCH,Ph

- =\ro' , - H,C

0

0 CH,=C,

,o-r;

I1 0-

CO,H

OCHzPh

In the case of the monobenzyl ester (21), the necessary pseudorotation should be less favourable since it requires the 0-to be apical, and in accord with this there was no monobenzyl phosphate produced when the solvolysis was conducted in the presence of hydroxylamine. A similar migration29 has been observed in S-alkyl esters of phosphonothiolic acid bearing a vicinal hydroxy-group (22), in which, when R2= OMe, OEt, or OPr', the products of base solvolysis are those expected from a complete migration of the phosphonyl group. When R2 = Ph, R1= Et, this pathway accounted for less than 30% of the reaction, and with R2 = 0-, R1= Me, or Et, no migration was observed. These results doubtless reflect the relative energy barriers to placing a phenyl or 0group apical in the pentacovalent intermediate. A somewhat unexpected result observed was the fact that base-catalysed opening of the cyclic derivatives (23) and (24) proceeded with almost exclusive P-0 fission as a9

S. J. Benkovic and K. J. Schray, J. Amer. Chem. SOC.,1969, 91, 5653. D. C. Gay and N. K. Hamer, J. Chem. SOC.(C), 1970, 1123.

Qwhquevalent Phosphorus Acids 101 whereas analogous acyclic esters underwent P-S cleavage. A parallel mechanism must be invoked to account for the formation of (25) from the reaction of epichlorhydrin with 00-diethylpho~phorodithioate.~~ CH20H 0 I Il OR1 CH2S -P' ' K 2

(22)

CH2Cl I

CH,o

CH,/

cx, (23 R2 = Ph)

(24

R2 =

0-)

CH2C1 I (Et0)2P(~1J 4 CHOH S

I

Et. N

yH"s

YH2'*

CH,.S*P(OEt I/ )2 --k+ CH2* S * PI1(OEt)2 (25)

A study has been made of nucleophilic displacement of ArO- from a series of triesters (26) in the presence of a wide range of nu~leophiles.~~ The Brlzrnsted plots (Ar varied) for strongly basic nucleophiles (HO-, NO2-, CF3CH20-)had small slopes (- 0-35),which rose as the basicity of the nucleophile decreased, rising to 0.99 for water. A significant solvent isotope effect was found for the more weakly basic nucleophiles, and this was interpreted in terms of a change from nucleophilic attack to generalbase catalysis as the basicity of the leaving-group became greater than that of the nucleophile. The rate constants with either Ar or nucleophile constant gave a reasonable fit to a four-parameter equation. The monoanions of diesters of phosphoric acid are relatively inert to nucleophilic attack unless one, at least, of the esterified groups is a good leaving-group. However, if this latter condition is satisfied, then attack by water and other nucleophiles32on phosphorus may be observed, and appears to follow a straightforward SN2(P) mechanism, although it is possible that a pentacovalent intermediate was involved. Not unexpectedly, there appears to be a considerable electrostatic effect inhibiting attack by anions, but otherwise the relative reactivity of various nucleophilic species qualitatively parallels that observed for reaction with many fully esterified derivatives of phosphoric acid. Intramolecular nucleophilic catalysis by the o-carboxy-group33 appears to be important in the solvolysis of the diary1 phosphates (27), since in the pH range where the carboxylic acid group is ionised, the hydrolysis proceeds 10'-lo8 times faster than similar derivatives lacking the o-carboxy-group. The intramolecular attack so s1 3a

s3

0. N. Nuretdinova and B. A. Arbusov, Izuest. Akad. Nauk S.S.S.R.,Ser. khim., 1970, 145. S. A. Khan and A. J. Kirby, J. Chem. SOC.(B), 1970, 1172. A. J. Kirby and M. Younas, J. Chem. SOC.(B), 1970, 510, 1165. S. A. Khan, A. J. Kirby, M. Wakselman, D. P. Horning, and J. M. Lawler, J. Chem. SOC.(B), 1970, 1182.

102

Organophosphorus Chemistry n

proceeded, as might be expected from results on (21) and (22), with exclusive expulsion of ArO- rather than migration, and the intermediacy of the cyclic acyl phosphate was demonstrated. Acid-catalysed hydrolysis 34 of di- and tri-aryl phosphates of low basicity is assisted by electron-withdrawing substituents, and there is no l80 exchange with labelled water. Using estimated values for the pK,'s, it was found that the rate maxima occurred well below complete protonation of the solvent, suggesting that in strongly acidic solution proton transfer to the substrate is partially rate-limiting. The effect of solvent variation indicated that initial-state effects may also be important in these systems. Acid-catalysed solvolytic mechanisms have also been found for p-chloroand p-bromo-substituted phenyl phosphate^,^^ but none was observed in the case of o- or p-methoxy-substituted derivative^.^^ Catalysis of the reaction of F- and OH- with diphenyl p-nitrophenyl phosphate (28) by cationic detergent micelles of acetyltrimethylammonium bromide has been dem~nstrated,~' and this catalysis is inhibited by aryl phosphate ions owing to competition for the available sites. Similarly, the rates of micelle-catalysed reaction of phosphate dianions with the same > HPOk2substrate follow the order p-But C6H40P02-> C6H50P032rather than the relative nucleophilicities, and is consistent with increased binding to the micelle of those anions with large hydrocarbon side-chains. Anionic detergent micelles (sodium lauryl sulphonate) are effective in catalysing the acid hydrolysis of diethyl a-phenylvinyl phosphate,38 which appears, on the basis of H b dependence, AS*, and ~ H ~ o / ~ D ,to o , follow an ASE2pathway. Hydroxide ion attacks the dianion of 2,4-dinitrophenyl phosphate 38 (as does water itself) principally at phosphorus, a somewhat unexpected result in view of the unfavourable electrostatic situation. The more polarisable alkoxide ions, however, attack mainly on the aryl ring. The rate of hydrolysis of tri-isopropyl and tri-t-butyl phosphates are unaffected by hydroxide ion up to concentrations of 0.1 moll-l; studies in mixed solvent systems indicate that they proceed by a S,l mechani~rn.~O 34

36 36 37 38 39 40

C. A. Bunton and S. J. Furber, J . Org. Chem., 1969, 34, 3396. M. M. Mhala, M. D. Patwardhan, and K. R. Kasturi, Indian J . Chem., 1969, 7 , 145. M. M. Mhala, C. P. Hollas, G . Kasturi, and K. Gupta, Indian J. Chem., 1970, 8, 51. C. A. Bunton, L. Robinson, and L. Sepulveda, J. Amer. Chem. SOC.,1969, 91, 4813. C. A. Bunton and L. Robinson, J . Amer. Chem. SOC.,1969,91, 6072. C. A. Bunton and J. M. Hellyer, J . Org. Chem., 1969, 34, 2798. J. R. Cox and M. G . Newton, J . Org. Chem., 1969,34,2600.

Quinquevalent Phosphorus Acids 103 An acid-catalysed solvolytic mechanism for trimethyl phosphate (also with C-0 fission) becomes important in solvents of low water activity.41 There have also been reported rate studies in 000-trimethyl phosphorothioate and 00s-trimethyl p h o s p h ~ r o t h i o a t e43 .~~~ The effect of bulky acyl groups on the hydrolysis of some acyl phosphates (29; R = Me,CH, Me,C.CH,, Me,CH.CH,) has been studied 44 although, apart from a general rate decrease with increasing bulk and electrondonating ability of the alkyl group, the general behaviour of the mono- or di-anions is similar to other acyl phosphates. Pyridine attack occurs mainly at phosphorus, and the rates correlate with D* values of the alkyl group. Divalent metal cations catalyse the hydrolysis of acetyl phoshate,^^ but under these conditions acyl oxygen cleavage occurs. The cyclic acyl phosphate (30) unlike the related anhydride of phosphoenol pyruvate (3 l), undergoes hydrolytic attack exclusively at the carbony1 group. Ph RC0.0.P03H2 (29)

0, 4’

%‘‘oE~ 0 (30)

0,$3

H,C

I o A0-

0

(3 1)

The three pyridyl methyl phosphates show characteristic rate maxima at pH- 2-5, where they exist predominantly as the neutral zwitterion; there is also a slower hydrolytic contribution from the m ~ n o a n i o n . ~ ~ Intramolecular proton transfer is suggested to account for the large rateconstant of the 2-isomer. The rates of hydrolysis of the 3- and 4-isomers are unaffected by divalent metal cations, but the 2-isomer and the quinoline derivative (32) are specifically catalysed by Cu2+,which is almost certainly

OH

OPO,H, (32) 41

42

43 44

45 46

47

P. T. McTigue and P. V. Renowden, Austral. J. Chem., 1970, 23,297. V. E. Bels’kii, N. N. Bezzubova, V. N. Elisenkov, and A. N. Pudovik, Zhur. obshchei Khim., 1969, 39, 1011. J. Masse and F. Sabon, Trau. SOC.Pharm., Montpellier, 1969, 29, 73. D. R. Phillips and T. H. Fife, J . Org. Chem., 1969, 34, 2710. P. J. Briggs, D. P. N. Satchell, and G. F. White, J. Chem. SOC. (B), 1970, 1008. J. F. Maracek and D. L. Griffiths, J . Amer. Chem. SOC.,1970, 92, 917. Y. Murakami and M. Tagaki, J . Amer. Chem. SOC.,1969,91, 5130.

104

Organophosphorus Chemistry

due to chelation since Cu2+forms very stable chelate complexes with the hydrolysis product. In the presence of Th4+ all these compounds (and several other monoesterified phosphates) underwent rapid h y d r o l y s i ~ , ~ ~ but the mechanism here is presumably quite different. Solvolysis of a series of N-phosphorylated pyridines in the presence of a series of nucleophiles 4s showed that, while the rate of nucleophilic attack is relatively insensitive to basicity, it is strongly dependent on the detailed structure of the nucleophile. It is suggested that, contrary to earlier views, this is not a consequence of a small degree of bond formation in the transition state, but that the attack on phosphorus derives considerable electrostatic assistance from the developing positive charge on the nucleophile and the negative charge on the phosphate, which tends to compensate for change in basicity of the nucleophile. The low nucleophilic reactivity of NH, and imidazole is accommodated on the basis that these may disperse the positive charge by hydrogen-bonding and delocalisation respectively. The rate profile for the hydrolysis of some S-aryl phosphorothioates 6O is typical of reaction involving both neutral molecule and monoanion. With an o-carboxyl substituent (33), a substantial but not spectacular increase ( 5 x ) in rate was observed. Unlike the related derivative (27), this does not appear to be due to nucleophilic catalysis by the carboxygroup. The solvent isotope effect was not inconsistent with a ratedetermining intramolecular proton transfer, but it is possible that steric facilitation may also be operative. N

nS.P03H2 Rates of exchange of radio-chloride with dialkyl phosphorochloridates in acetonitrile solution have been measured61 and the relative values of AS* and AH* are roughly parallel to those observed for attack by other nucleophiles, C. Reactions.-The phosphoryl oxygen is generally considered a poor nucleophile; nevertheless, addition is possible with very strong electrophiles. Trialkyloxonium fluoroborates add to trialkyl phosphate giving tetra-alkoxyphosphonium salts.62 The cyclic ester (34), however, did not react, and tetramethylethylene ethyl phosphate rearranged to pinacolone. Somewhat analogous adducts (35, R = Buy Ph, or NMe,) have been Y . Murakami and M. Tagaki, Bull. Chem. SOC.Japan, 1969,42, 3478; Y . Murakami, J. Sunamoto, and H. Sadamori, Chem. Comm., 1969,983. I s G. W. Jamieson and J. M. Lawler, J . Chem. SOC.(B), 1970, 53. 6 o T. H. Fife and S. Milstein, J. Org. Chem., 1969, 34,4007. M. Mikolajczyk, J. Michalski, A. Halpern, and R. Sochazcka, Monatsh., 1969, 100, 1266. 63 J. H. Finley, D. Z . Denney, and D. B. Denney, J. Amer. Chem. SOC.,1969, 91, 5826.

Quinquevalent Phosphorus Acids 105 obtained from the reaction of phosphoryl or thiophosphoryl chloride with the appropriate R3P0.53

c1

+

(34)

/

R,P-O--P--CI \\ X (3 5 )

c1-

There is evidence that the cyclic phosphates (36) and (37) undergo A interconversion concomitant with hydrolysis in aqueous mixture of initial composition 87% (36) and 13% (37), obtained from oxidation of the corresponding phosphite, rapidly gave an equilibrium concentration of 61% (36) and 39% (37) on partial hydrolysis, which proportions did not change significantly as hydrolysis continued further. This result is explicable if the initial addition of water to give a pentacovalent intermediate is reversible; however, such a process, although quite feasible, has not hitherto been observed in a fully esterified derivative. The cyclic phosphorochloridate (38) gives a mixture of isomers (39) and (40) on solvolysis in methanol, and these isomers are conformationally In the presence of Agf, the solvolysisleads to (40) exclusively and a S,l(P) mechanism has been suggested to account for this.

(37)

54

55

OH

H. Binder and E. Fluck, Z. anorg. Chem., 1969,365, 170. D. Z. Denney, G. Y. Chen, and D. B. Denney, J. Amer. Chem. SOC.,1969,91, 6838. W. Wadsworth and H. Horton, J. Amer. Chem. Sac., 1970, 92, 3785.

Organophosphorus Chemistry

106

0-Serine pyrophosphate (41) is rapidly hydrolysed at pH 9 to 0-serine phosphate, whereas the NW-diacetyl derivative is suggesting that intramolecular nucleophilic catalysis by the carboxylate ion, as was found in (27), is not important here. In the presence of excess aqueous methylamine, a mixture of N- and 0-serine phosphates was obtained. It is 0 0 IIf'l II CH2-O--P-O--P-OCH2 I fL I I CH2-NH 0- CH(NH,)CO,H

I

C02H

\

CH2-0, I CH- N H/ I CO,H

H

40

'\o-

probable (indeed almost certain in the latter case) that the cyclic phosphoramidate (42) is an intermediate, and the differing products may reflect a different mode of opening of this, according to whether a neutral or base-catalysed solvolytic process operates. The phosphorimide (43) rearranges thermally,57 in a manner which parallels the Claisen ally1 ether rearrangement, to give a phosphoramidate (44). Pyrolytic studies on esters and salts of phosphoric acid5*indicate the reaction to be complex, giving a variety of products. However, the thermal elimination of diethylphosphoric acid from compounds (45) ( R10)2P=N-Ph /

0 \

C H R I C H = CHR2

-

N( Ph) CHR2*CH=CHR1

A +

(R'O) P< 0 '

(44) (43)

Ero o

0 ( E t O).,PH 0

II

HCN

II

i

R C I - I , C O C l a RCHZ*CO*P(OEt), -+ RCI-I,.C-P(OEt),

I

CN

1" 66

57

58

S. M. Avaeva, V. A. Sklyankina, and M. M. Botvinik, Zhur. obshchei Khim., 1969,39, 591. A. N. Pudovik, I. M. Aladzheva, and V. G. Kotova, Zhur. obshchei Khim., 1969, 39, 1528. J. Devilliers, N. Michel, J.-P. Vjves, and J. Narech, Bull. SOC.chim. France, 1969, 2407.

Quinquevalent Phosphorus Acids 107 appears to provide a synthetically useful route to @-unsaturated nitriles 6D from acid chlorides with one less carbon atom. Thermal decomposition of the t-butyl peroxyphosphate dialkyl esters gives rise to acetone, t-butanol, the dialkyl phosphate, and the tetra-alkyl pyrophosphate as main products,60*61 and these are adequately rationalised on the basis of initial homolytic fission of the 0-0 bond. S-Phosphoryl sulphenamides (46) react with 00-dialkyl phosphorodithioates to give the disulphide;62 when R1# R2, only symmetrical disulphides are obtained, indicating a facile disproportionation. The related toluene-p-sulphonyl derivatives (47) are formed in the reaction of phosphorylated sulphenyl chlorides with the anion of toluene-p-sulphonamide.53 These react with acidified KI solution to give (48) or (49) according to the conditions.

S

II

+ T ~ ~ ~ ~ - N H - S - - P ( O R )$-, TOSYI-NH, (48)

3,5-Dimethoxybenzyl phosphate is dephosphorylated on irradiation in aqueous solution 64 and, by analogy with the corresponding acetate, C-0 cleavage by an ionisation mechanism is suggested. C-0 Cleavage may also be observed in reactions of the cyclic esters (50;X = S,0; Y = Ph or NR2) and (51 ; Y = Ph) with trimethylamine. When Y = OMe, however, demethylation preferentially occurs.66

(50) 69

6o

63 64

6s

(51)

Y. Okamoto, T. Nitta, and H. Sakurai, J. Chem. SOC.Japan, Znd. Chem. Sect., 1969, 71, 187. V. P. Mastennikov, V. P. Sergeeva, and V. A. Shushmor, Zhur. obshchei Khim., 1969, 39, 2234. G . Sosnovsky, Intra. Sci. Chem. Reports, 1969, 3, 275. L. Almari and A. Hantz, Monatsh., 1969, 100, 798. L. Almari and A. Hantz, Chem. Ber., 1970, 103, 718. V. M. Clark, 5. B. Hobbs, and D. W. Hutchinson, Chem. Comm., 1970, 339. P. Chabrier, Nguyen Thanh-Thuong, and D. Le Maitre, Compt. rend., 1969,268, C, 1802.

108

Organophosphorus Chemistry

The thermal rearrangement of 000-trialkyl phosphorothioates to give first 00s-trialkyl phosphorothioates and then thioethers has been investigated.g6 It is likely that both reactions involve a bimolecular attack by the substituted sulphur atom of one molecule on an alkoxy-group of another molecule. A similar process doubtless occurs in the thermal reaction of both isomeric cyclic phosphoramidothioic chlorides (52) and (53), which give rise to (54).67 Me

2 Phosphonic and Phosphinic Acids and Derivatives A. Synthetic Methods.-There has been reported a great amount of preparative work on both cyclic and acyclic derivatives of these acids using established methods. Since almost all involve reaction of a tervalent phosphorus derivative with various electrophilic species, only a few can be given here. A simple preparation of esters of ethynylphosphonic acid6* has been reported, involving an Arbusov reaction of trimethylsilylchloroacetylene with a trialkyl phosphite to give (55), from which the protecting group is removed by mild base treatment. When R = Pri, the intermediate was thermally labile, eliminating propylene to give (56) and an intermolecular mechanism was tentatively suggested. Propynyl- l-phosphonic acid (from the acetylenic Grignard reagent and dibutyl phosphorochloridate) has been used as the starting point for syntheses 'O of the antibiotic phosphonomycin (57), whose structure has been firmly established. 2-Hydroxyethylphosphonic acid is obtained by hydrolysis of 2-chloroethylphosphonic acid at pH l,?lwhereas basic hydrolysis is well known to cause elimination with formation of inorganic phosphate and ethylene. In contrast, 2-chloro-1-hydroxypropylphosphonic acid rearranges rapidly in base (more slowly in acid) with phosphoryl migration to l-formylethylphosphonic acid (58).?O 699

-=

66 67 88 69

'O

R. R. Engel and D. Liotta, J. Chem. SOC.(C), 1969, 2731. P. Savignac, J. Chenault, and P. Chabrier, Compt. rend., 1970, 270, C, 2086. D. W. Burt and P. Simpson, J. Chem. SOC.(C), 1969,2273. B. G. Christensen, W. Leanza, T. R. Beattie, A. A. Patchett, B. H. Arison, R. E. Ormond, and F. A. Kuehl, Science, 1969, 166, 123. N. N. Girota and N. L. Wendler, Tetrahedron Letters, 1969, 4647.

Quinquevalent Phosphorus Acids (KO),P -I- ClC-CSiMc,

109 3 (RO),P(:O)*CSCSiMe,

a/ PriO\

/p

/R

P Me,SiO’ ‘C-CH

CICH,CH, *PO,H, :OH “13; H H.-H

Me

PO,H,

(55) = PI’)

(RO),P(:O)-C-CH

H,O

d

MOCH ,CH,PO,H,

CH,.CH*P0,H2

I

CHO (58)

The novel polyphosphonic acids (59) and (60) 7 2 are simply obtained by addition of diethyl phosphite anion to propargyl alcohol and but-2-yne1,4-diol, followed by hydrolysis. Reaction of 3-chloro-3-methylbutyne with the anion of diethyl phosphite, however, gives, as a primary product, the allenephosphonic ester (61).73 This may arise by addition of the carbene (62) to the phosphite or by rearrangement of the initially formed acetylenic phosphite (63), which is known to be p~ssible.’~ The phosphonamide (64) is formed on thermal rearrangement of diphenoxy-NN-diethylaminophosphine (65),75 which is somewhat surprising in view of the difficulty of nucleophilic attack on aryl rings. It is possible that this rearrangement is intramolecular rather than of the classical Arbusov type. The stable phosphinimidic chloride (66) has been prepared from ammonia and bistrichloromethyl phosphorus trichloride ‘13 and is monomeric. 71

72 73 74 76

76

W. Vogt, Tetrahedron Letters, 1970, 1281; see also ref. 134 on p. 165 of last year’s Report. W. A. Cilley, D. A. Nicholson, and D. Campbell, J. Amer. Chem. SOC., 1970,92, 1685. A. N. Pudovik and N. G. Khusainova, Zhur. obshchei Khim., 1969, 39, 1646. A. N. Pudovik and I. M. Aladzhyeva, Zhur. obshchei Khim., 1963,33, 3096. A. N. Pudovik and V. K. Krupnov, Zhur. obshchei Khim., 1969, 39, 1890. E. S. Kozlov, S. N. Gaidamaka, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 1648.

110

Organophosphorus Chemistry CH,-CH-CH2P03H2

I

CHZ-CH-CH-CHZ I I I I P03H2 P03H2 P03H2 PO&,

I

P03H2 PO$,

(60)

(59)

P

n

H-CrC-C(Me),-Cl

P + :C=C=CMe,

7

(EtO),PO-

Me,C=C=P(:O)OEt

I

OEt (61)

Me I CH rC-C-OP(OEt)

I

2

Me (63)

(1

Reaction of phosphorus pentachloride with 1,l-diethoxyethane gives a bulky precipitate, which is decomposed by SO, to the phosphonic acid dichloride (67) 77 in a remarkably high yield. Although the structure of the intermediate is not yet known, it is possible that the attack is initiated by a hydride transfer to phosphorus leading to the keten acetal, which then undergoes electrophilic attack.

,

( Et 0) C =CHPOCI,

(67) 77

V. V. Moskova, I. S . Gusera, and F. P. L‘Vova, Khim. Atsetilena, 1968, 175.

Quinquevalent Phosphorus Acids 111 Hypophosphorous acid reacts in a similar manner to phosphorous acid with carboxylic acid anhydrides, giving acyl phosphinates (68). With strong base, these disproportionate to the 1 -hydroxyalkylidinediphosphinicacids, which may be oxidised by iodine to the corresponding phosphonic 0 0 4 4 RCO*O*COR H,PO,. RC-P-H

+

\

OH

-(W

1-Diazoalkylphosphonic esters (69; R1= OMe, OEt; R2= Ar, C02Et, or COPh) may be prepared by the reaction of toluene-p-sulphonyl azide 7B and base with the appropriate phosphonates. The unsubstituted diazomethylphosphinic ester (69; R1= OEt, R2 = H) 80a was obtained from the

Ph I ,h>CH-p=O

R2

OCHS

reaction between toluene-p-sulphonyl azide and base and the diethyl ester of acetaldehyde-2-phosphonicacid, or, more simply, by diazotisation of the corresponding amine.80b On irradiation, they give the a-phosphonyl carbenes, which undergo typical hydrogen abstraction and insertion reactions; in addition, when R1= Ph, R2 = H, COPh, or C02Et, a phosphorus analogue of the Wolff rearrangement occurred, to give the phosphinic acid. F. Kasparek, Monatsh., 1969, 100, 2013. M. Regutz, H. Scherer, and W. Anschiitz, Tetrahedron Letters, 1970, 753. n o a M. Regitz and W. Anschutz, Annalen, 1969,730,194; D. Seyferth and R. S. Marmor, Tetrahedron Letters, 1970, 2493.

7*

70

112

Organophosphorus Chemistry

00-Dialkyl selenophosphonates (70) have been prepared by treatment of the chlorides with H2Sein the presence of triethylamine.sl

(70)

The preparation of an ATP analogue possessing methylene bridges between the phosphorus atoms has been achieveds2 by condensing the triphosphonic acid (7 1) [from Arbusov reaction on bis(chloromethy1)phosphonic acid 83] with adenosine using dicyclohexylcarbodi-imide (DCC). In the absence of nucleophiles, reaction of the acid (71) with DCC gave the methylene analogue of the cyclic trimetaphosphate ion. 0 II H203P-CH2-P-CHzP03H, I OH

HO, DCC

HzC’

I

HO-P,

C?

P

&O

‘YHz ,P=O

‘OH

(71)

B. Solvolyses of Phosphonic and Phosphinic Esters.-An intriguing neighbouring-group effect has been observed in the hydroxide-catalysed elimination of p-nitrophenol from the syn and anti isomers of oximinophenacyl p-nitrophenyl rnethylphosphonate (72a) and (72b).84 This proceeds loa and lo7 times faster than that from the corresponding ethyl ester, and also considerably faster than from phenacyl p-nitrophenyl methylphosphonate itself. Since nucleophilic participation by the oxime hydroxygroup is impossible in the anti isomer, the authors favour an intramolecular general-base catalysis. In the opinion of the Reporter, the high solvolytic rates seem abnormally large for such a mechanism-particularly in the case of the anti isomer, which would require a high degree of order in the transition state. Until the precise structure of the phosphorus-containing products are established, other mechanisms, including a rate-determining anti --f syn isomerisation for (72b), cannot be entirely excluded. The base hydrolysis of Sarin (73) is catalysed by cyclodextrin, the rates of the two enantiomers differing; that of the (It)(-), which forms the less-stable complex with the catalyst, is greater than that of the (S)(+),s5 As has been observed with similarly catalysed reactions, the rate constants do not vary linearly with cyclodextrin concentration but approach saturation values. The reaction of Sarin with anhydrous HC1 shows a thirdorder kinetic dependence.86 81

82

83 84

85 86

C. Krawieki, J. Michalski, R. A. Y. Jones, and A. R. Katritzky, Roczniki Chem., 1969, 43, 869. D. B. Trowbridge and G. L. Kenyon, J. Amer. Chem. SOC.,1970, 92, 2181. L. Maier, Helu. Chim. A d a , 1969, 52, 827. C. N. Lieske, J. W. Hovanec, and P. Blumbergs, Chem. Comm., 1969, 976. C. Van Hooidonk and J. C. A. E. Breebaart-Hansen, Rec. trav. chim.,1970, 89, 289. J. R. Bard, L. W. Daasch, and H. Klapper, J. Chem. and Eng. Data, 1970, 15, 134.

Quinquevalent Phosphorus Acids N-OH

0 ll Ph.C-CH,O-P --Me

II

113 HO-N

II

0

II Ph-C*CH20- P -Me

I

I

0 II

PriO-P-F

I Me (73)

The aqueous hydrolysis of a series of dialkyl phosphonates proceeds with P-0 cleavage, and the rates correlate with the Taft (T* values associated with the alkyl Fully esterified phosphonates 88 and phosphinates 89 appear, like many phosphate triesters, to undergo neutral solvolysis on the alkyl oxygen cleavage, and esters of secondary and tertiary alcohols follow an SN1 mechanism. Nucleophilic attack on dialkyl acylphosphonates occurs at carbon with expulsion of dialkyl phosphite anion.9o The attack of hydroxide ion on ethyl bis(dichlorornethy1)phosphinothioate (74) occurs on phosphorus, and is faster than the corresponding oxygen The anion of the phosphinothioate also undergoes rapid loss of chloride (unlike the corresponding phosphinate ion) giving the four-membered ring compound (75).92 Trichlorophos-T (76) rearranges readily under basic conditions to 2,2-dichlorovinyl dimethyl phosphate, and using 3H-labelled substrate it was found that the product contained 0-83 atommol-l of tritium in the vinyl group, supporting the proposed mechanism.93 The formation of 87

@O

B2

O3

V. E. Belskii, G. Z . Motygullin, V. N. Eliseenkov, and A. N. Pudovik, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1297. V. E. Belskii, G. Z. Motygullin, and 0. N. Grishina, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 2813. V. E. Belskii, M. V. Efremova, I. M. Shermergorn, and A. N. Pudovik, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 307. A. P. Pashukin, T. K. Gazizov, and A. N. Pudovik, Zhur. obshchei khim., 1970,40,28. V. E. Belskii, L. S. Andreeva, and I. M. Shermergorn, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 2812. N. V. Ivasyvak and I. M. Shermergorn, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 481. W. Dedek, H. Koch, G. Uhlenhut, and F. Broese, 2. Naturforsch., 1969, 24b, 663.

Organophosphorus Chemistry

114

(74)

F H 2 ,

-LcH;p:o-, -S-CH2

/p

S%H2/ P‘0(75)

0

Ql

tributyl phosphate from the related (77)with sodium hydroxide in butanol O4 doubtless follows a similar route involving an initial deacylation and finally an ester exchange reaction.

c1

/

0’

40 (Bu0)2P, CH(OAc)CCI,

BuOH base

,C-Cl \L Cl

’ (B u 0)3P=0

(77)

Hydrolysis of the cyclic anhydride (78) in H2l 8 0 indicates that attack proceeds with comparable facility on the carbonyl and phosphinyl groups.g6 The interpretation is, however, complicated owing to the fact that there was evidence that l 8 0 exchange could occur between the carboxyl and phosphinyl group in the product. P P P O 0’ ‘Et

0

u4

N. N. Mel’nikov, K. D. Shetsova-Shilovskaya, and I. L. Bogatyrev, Zhur. obshchei

85

Khim., 1969, 39, 2370. Y. Y . Efremov and V. K. Khairullin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 23 14.

115

Quinquevalent Phosphorus Acids

C. Reactions of Phosphonic and Phosphinic Acid Derivatives.-The optically active dithiopyrophosphonate (79) gave, as expected, optically active products with methoxide, but with lithium diethylamide a racemic

s

II EtO-P-0-P I Et

s I1

I

S -0Et

Et

Et NU

II

2EtO-P-NEt, I

Et

arnide was produced.ss I t was shown that the optically active amide did not racemise in the presence of the reagent, and it was therefore suggested that a pentacovalent intermediate was formed whose rate of breakdown was slow compared to the rate of pseudorotation. Using 2H-labelled substrate, it has been demonstrated that both isomers of l-rnethoxy-2,2,3,4,4-pentamethyl phosphetan-1-oxide (80) undergo methoxy-group exchanges with retention of configurati~n,~~ a result which was simply explained in terms of the preferred pseudorotational conformers of the pentacovalent intermediate.

Photochemical studies have been reported on various a-ketophosphonate esters (81). Irradiation of the n -+T* absorption region of the carbonyl group results in intermolecular hydrogen abstraction leading to pinacol formation when R1= Ar, R2 = Et, Pri, But, except with R1= Ph, R2 = Et, when the trioxan (82) is almost the sole The reason for the anomalous behaviour is not yet clear. With R1= Me, R2, R3= alkyl, intramolecular hydrogen abstraction from the alkoxy-group was and the products were rationalised in terms of the resulting biradical. Vinyl and acetylenic phosphonic acid derivatives behave as dienophiles, and in the reaction of [83; R2= C1 or (R10)2PO] with cyclopentadiene, 96

O7

9g 8s

M. Micolajczyk, J. Omelanczuk, and J. Michalski, Bull. Acad. polon. Sci., Sdr. Sci. chim., 1968, 16, 615. S. H. Cremer and B. C. Triveda, J . Amer. Chem. SOC.,1969, 91, 7200. K. Teranchi and H. Sakurai, Bull. Chem. SOC.Japan, 1970, 43, 883. Y. Ogata and H. Tomioka, J. Org. Chem., 1970, 35, 596.

116

Organophosphorus Chemistry

cyclohexadiene, or diazomethane, the expected adducts were formed.loO The dimer of the diethyl ester of buta-l,3-dienyl-l-phosphonic'acid has been shown to have the structure (84).lo1

OH .CR2R3

1 R1-C.>

o,

1

.'::pI! OCHR2R3 \

/

0

Y

P 0 CHR2R3 OH

&

R2R3

J

R'y ! 1 0 C € - I R 2 R 3

---+

0 II R1COCR2R3P 1 OCHR2R3 OH 0

The phosphinate ester (85) (from hypophosphorous acid and the diol) appears to exist in equilibrium with the cyclic form. Treatment of (85) with diazomethane gives 'the very labile phosphine (86),lo2 which reacts with 2-sulsulphur to give the known 5,5-dimethyl-l,3,2-dioxaphosphorinane phide. loo lol lo2

D. Seyferth and J. D. H. Paetsch, J . Org. Chem., 1969, 34, 1483. C. E. Griffin and W. M. Daniewski, J. Org. Chem., 1970, 35, 1691. E. E. Nifantev and L. M. Matveeva, Zhur. obshchei Khim., 1969, 39, 1555.

117

Quinquevalent Phosphorus Acids H.,

H 2

c-0 s

Me,C

/

\/

\

/\

C-0 H?.

P

H

Diphenyl phosphinothioic chloride and related active esters of the same acid have been investigated as potential reagents for radioactive labelling of imrnunoglob~lins.~~~

3 Miscellaneous An X-ray crystal study on 2-hydroxy-2-oxa-l,3,2,-dioxaphosphorinane (87; R = OH) shows that its structure, like other members of this ring system which have been determined, is a chair conformation in which the

(87)

angles around phosphorus are close to tetrahedral.lo4 N.m.r. studies indicate that in most cases, except where R = Ph, the P=O group preferentially adopts the equatorial position. There appears to be some conflicting evidence as to the extent of conformational mobility of this system. Variable-temperature n.m.r. studies and analysis of coupling coefficients on a wide range of derivatives have been interpreted in terms of reasonably facile conformational changes.lo5,lo6 However, other n.m.r. studies lo7 and some strong chemical evidence on the non-interconvertibility of (39) and (40)appear to rule out the possibility of interconversion between the two chair forms. It may turn out that this is critically dependent on the nature of the substituents. The conformations of the 1,3,2-dioxaphospholan derivatives (88) and dioxaphosphorinane (89) have been assigned on the basis of preparation from the phosphites and sulphur, in a reaction whose stereochemistry is R. A. Spence, J. M. Swan, and S. H. B. Wright, Austral. J. Chem., 1969, 22,2359. Mazhar-ul-Haque, C. N. Caughlan, and W. L. Moats, J. Org. Chem., 1970, 35, 1446. l o 6 R. S. Edmundsen and E. W. Mitchell, J . Chem. SOC. ( C ) , 1970, 1001. lo6 A. R. Katritzky, M. R. Nesbit, J. Michalski, Z. Tulimowski, and A. Zwierak, J. Chem. SOC.(B), 1970, 510. lo' M. Kainosho and A. Nakamura, Bull. Chem. SOC. Japan, 1969, 42, 1713. lo3 lo4

5

118

Organophosphorus Chemistry

established. l o 8 It appeared that trimethylamine dealkylates only isomer (89), in which the methyl group is cis to the phosphoryl P=S, presumably due to steric hindrance.log

ty?

Me

0 bMe

J>P&

(894

(88)

(89W

The absolute configuration of some optically active phosphonothioate esters has been deduced from the partial reduction of racemic dialkyl su1phoxides.ll0 Assignments on this basis were in agreement with those deduced from the lH n.m.r. spectrum of the a-phenylethylamine salts.111 Values of the Hammett (T have been measured from the dissociation constants of a series of m- andp-substituted benzoic acids (90; R = alkyl, OR, X = S or 0)112 and have been estimated from the laFshift 113 in the n.m.r. spectra of a series of 3-substituted fluorobenzenes. When R = phenyl, the two sets are in good agreement, but this is less so when R = alkoxy. Crystal structure determinations have been carried out on the phospholan (91),114 pyridoxal phosphate,l15 ATP,lls and OO-uridine-2’,3’cyclic-phosphorothioate.117

(90) lo9 111 112

11*

116 110

(91)

M. Micolajczyk, and H. M. Schiekel, Angew. Chem. Internat. Edn., 1969, 8, 511. M. Micolajczyk,Angew. Chem. Internat. Edn, 1969, 8, 511. M. Micolajczyk and M. Para, Chem. Comm., 1969, 1192. M. Micolajczyk, Chem. Comm., 1970, 654. E. N. Tvsetkov, D. I. Lobanov, L. A. Isosenkova, and M. I. Kabachnik, Zhur. obshchei Khim., 1969,39, 2177. H. Schindlbauer and W. Prikoszovich, Chem. Ber., 1969, 102, 2914. E. Alver and H. M. Kjnge, Acta Chem. Scand., 1969,23, 1101. T. Fujiwara and K. Tomita, Tetrahedron Letters, 1969, 2819. 0. Kennard, N. W. Isaacs, J. C. Coppola, A. J. Kirby, S. Warren, W. D. S. Motherwell, D. G. Waton, D. L. Wampler, D. H. Chenery, A. C. Larson, K. A. Kerr, and L. Riva de Sanseverino, Nature, 1970, 225, 333. W. Saenger and F. Eckstein, Angew. Chem. Internat. Edn., 1969, 8, 595.

7 Phosphates and Phosphonates of Biochemical Interest BY D. W. HUTCHINSON

1 Mono-, Oligo-, and Poly-nucleotides A. Mononuc1eotides.-A considerable number of papers has appeared during the past year on the synthesis of phosphate esters of nucleosides, particular attention being paid to those compounds which might have interesting pharmaceutical properties. The phosphorylation of unprotected nucleosides, mentioned in last year’s Report,l has continued to be developed. For example, phosphorus oxychloride has been used to prepare the 5’-phosphates of inosine 1-oxide,2 2-metho~yinosine,~ and other nucleoti Good yields of nucleoside 5’-phosphates have been obtained by treating unprotected nucleosides with pyrophosphoryl chloride (1) in phenolic solvents,6 and GMP* has been prepared from 2’,3’-O-isopropylidene guanosine using the same reagent.’ The phosphorylation of adenosine and uridine * by inorganic phosphates and polyphosphates has been cited as evidence for prebiotic phosphorylation. It has now been reported lo that sodium trimetaphosphate will phosphorylate nucleosides specifically in the 2’- and 3’-positions in aqueous alkali. An interesting method for the selective phosphorylation of nucleosides in the 5’-position involves the use of diethyl azodicarboxylate (2), triphenyl phosphine, and 1

2

D. W. Hutchinson in ‘Organophosphorus Chemistry,’ ed. S. Trippett (Specialist Periodical Report), The Chemical Society, London, 1970, Vol. 1, p. 145. A. Yamazaki, I. Kumashiro, and T. Takenishi, Chem. andPharm. Bull. (Japan), 1969,

17, 1128. A. Yamazaki, T. Saito, Y. Yamada, and I. Kumashiro, Chem. andPharm. Bull. (Japan), 1969, 17, 2581. 0 Fr. P., 1,531,156 (Chem. Abs., 1969, 71, 91,829). 5 M. Yoshikawa, T. Kato, and T. Takenishi, Bull. Chem. SOC.Japan, 1969, 42, 3505; G. Donaldson, M. R. Atkinson, and A. W. Murray, Biochim. Biophys. Acta, 1969,184, 655. 6 K. Imai, S. Fujii, K. Takanohashi, Y. Furukawa, T. Masuda, and M. Honjo, J . Org. Chem., 1969,34, 1547. 7 W. A. Gaines and D. F. Reinhold, Fr. P. 1,538,161 (Chem. Abs., 1969, 71, 70,902). a A. Schwartz and C. Ponnamperuma, Nature, 1968, 218, 443. 0 J. Rabinowitz, S. Chang, and C. Ponnamperuma, Nature, 1968, 218, 442. 10 A. W. Schwartz, Chem. Comm., 1969, 1393. 3

* The abbreviations used for biochemical compounds in this review may be found in the Instructions to Authors of the Journal of Biological Chemistry.

120

Organophosphorus Chemistry

dibenzyl hydrogen ph0sphate.l’ Tt has been suggested that the initial step in the reaction is the formation of a phosphonium complex from (2) and triphenyl phosphine. The large size of this complex favours reaction with the unprotected nucleoside at the relatively unhindered 5’-position to give (3). Interaction of (3) with dibenzyl hydrogen phosphate gives the dibenzyl ester of the nucleoside 5’-phosphate. C1,P(O)OP(O)CI,

+I

(1)

EtO,CN=NCO,Et

0

+ Ph,P

Q

(PhCH,O) ?PO I‘

HO

+

OPPh,

------+ Et0,CN-N=C-OEt I

/-

(3)

+ Et0,CN H-NCO,Et

H

Ph,PO

+

EtO,CNHNHCO,Et

Nucleosides can undergo transesterification with triethyl phosphite to give cyclic esters e.g. (4), which can be dealkylated with ammonia producing (5) or the 2’-(3’)-phosphite. Oxidation of (5) with hexachloracetone yields the corresponding cyclic phosphate. In this way, the phosphate esters of a number of nucleosides which contain unusual sugars have been obtained.12 This method has also been used to prepare the 2’,3’-cyclic phosphate of homouridine (6),13 a compound which was completely resistant to hydrolysis by pancreatic RNase. The 5’-phosphate of ( 6 ) which was prepared by treatment of 2-cyanoethyl phosphate with dicyclohexylcarbodi-imide (DCC) was completely resistant to attack by snake venom 5’-nucleotidases. l1 l2 l5

0. Mitsunobu, K. Kato, and J. Kimura, J , Amer. Chem. SOC.,1969, 91, 6510. A, Holf and F. Sorm, Coil. Czech. Chem. Comm., 1969, 34, 1929, 3383, and 3523; A. Holf, ibid., 1969, 34, 3510. A. Holf, Coil. Czech. Chem. Comm., 1970, 35, 81.

Phosphates and Phosphonates of Biochemical Interest

121 2-Cyanoethyl phosphate and DCC have been used to phosphorylate 4-thiouridine (7) l4 and L-arabinosyluracil (8),16 when the 2‘-, 3’-, and 5’monophosphates of (7) and (8) were obtained after treatment of the inter-

I

OEt

(4)

HO l4 l5

(8) M. Saneyoshi and F. Sawada, Chem. and Pharm. Bull. (Jnpan), 1969, 17, 181. J. R. Boisser, P. Lepine, J. De Rudder, and M. Privat de Garille, Fr. M. 5616 (Chenr. Abs., 1969, 71, 70,901).

122

Organophosphorus Chemistry

mediate 2-cyanoethyl nucleoside phosphodiesters with alkali. With 2’-deoxynucleosides,e.g. N(4)-alkyl analogues of 5-methyl-2’-deoxycytidine, selective phosphorylation of the 5‘-hydroxy-group has been reported.lG The 5’-phosphate of 7-deaza-adenosine(sparsomycin) (9) has been prepared from the 2’,3’-O-isopropylidene nucleoside by the 2-cyanoethyl phosphate/ DCC method,17 and was used to prepare dinucleoside 2‘ + 5‘- and 3’ 5’phosphates, with DCC as condensing agent. The 2-cyanoethyl ester of 2’,5’-di-O-( 1-ethoxyethyl)uridine 3’-phosphate (10) has been coupled with 2’-0-(l-ethoxyethyl)uridine to give a reasonable yield of the 3’ -+ 5’-linked dinucleoside phosphate.18 Apparently little or no reaction takes place between (10) and the free 3’-hydroxy-group of 2’-0-( 1-ethoxyethy1)uridine. --f

\

HO’

OH

(9)

HO, NCCH,CH,O

/

/d P

‘b

\

OCHMe

I

OEt

The 2-(a-pyridyl)ethyl group (ll), which has been used as a base-labile protecting group for phosphoric acids,lg is not labile under conditions required for the removal of 0- and N-acetyl groups; its removal requires rather more forcing conditions. This makes possible the selective removal of protecting groups from nucleotides, and (1 1) could be of importance in oligonucleotide synthesis.lgb The removal of (1 1) with methoxide or butoxide ion presumably follows a pathway analogous to that for the cleavage of 2-cyanoethyl groups. The synthesis of nucleotides containing modified sugar residues has continued to receive attention; for example, 5’-amino-5’-deoxy analogues of nucleotides [e.g. (12)] have been prepared.20 Hydrolysis of (12) by snake venom phosphodiesterase yields the phosphoramidate (1 3) which rapidly breaks down in the pH range 6.5-10 to orthophosphate and the amine (14). Cytidine 2’,3’-cyclic phosphate (15) can be converted into aracytidine 3’-phosphate (17; B = C , R = H) by treatment with trimethylsilyl l6 l7 l9

2o

T. Kulikowski, B. Zmudzka, and D. Shugar, Acta Biochim. Polon., 1969,16,201 (Chem. A h . , 1969, 71, 91,808). A. R. Hanze, U.S.P. 3,337,530 (Chem. Abs., 1969, 71, 61,724). G. W. Grams and R. L. Letsinger, J . Org. Chem., 1970, 35, 868. a W. Freist, R. Hebig, and F. Cramer, Chem. Ber., 1970, 103, 1032; W. Freist and F. Cramer, Angew. Chem. Internat. Edn., 1970, 9, 368. B. Jastorff and H. Hettler, Chem. Ber., 1969, 102, 4119.

Phosphates and Phosphonates of Biochemical Interest

Meo-J 0

I

+

123

ROLF’O- + 0

II

MeOH

OH

Ro

::

H) p i

yo>=

phosphodiesterase

HO

(H 0

’

HO

(12)

(13)

H

HSPOd

+

HO

(14)

chloride.21 An intermediate in this reaction is 0(2),2’-anhydrocytidine 3’-phosphate (16), which undergoes hydrolysis in either aqueous alkali or bicarbonate to yield (17; B = C, R = H). Trimethylsilylated uridine and adenosine 2’,3’-cyclic phosphates did not react under comparable conditions. An alternative method for the synthesis of (17; B = C, R = H) under mild conditions consists of treating the N(4)-dimethylaminomethylene or 5’-ON(4)-diacetyl derivative of (15) with a sulphonyl chloride or diphenyl phosphorochloridate at room temperature in anhydrous Hydrolysis of the protected (16) followed by removal of the protecting groups gave (17; B = C , R = H) in high yield. This method has been applied to the synthesis of polyarauridylic acid from polyrU.22bDinucleoside phosphates, e.g. (17; B = U, R = uridine-5’) have been prepared by the 2-cyanoethyl phosphate/DCC method using a protected anhydron ~ c l e o s i d e(17; . ~ ~ B = U, R = uridine-5’) was cleaved by both snake venom and spleen phosphodiesterases. The preparation and properties of nucleotides containing modified bases have been reviewed24 and several papers have appeared on the 21 22

23 24

J. Nagyvary, J . Amer. Chem. SOL‘.,1969, 91, 5409. J. Nagyvary and C. M. Tapiero, Tetrahedron Letters, 1969, 3481 ; ,7 R. G. Provenzale and J. Nagyvary, Biochemistry, 1970, 9, 1744. K. K. Ogilvie and D. Iwacha, Canad. J . Chem., 1970, 48, 862. F. Cramer, Accounts Chem. Res., 1969, 2 , 3 3 8 .

a

Organophosphorus Chemistry

124

NH

J

o‘p
bromination of purine nucleoside phosphates and polyphosphates in the 26 Tosylation of either AMP or 8-bromo-AMP in alkaline 8-positi0n.~~~ solution gives mainly the 2’-tosyl derivati~e.~‘Treatment of 8-bromo2’-tosyl-AMP with sodium hydrosulphide gives 8,2’-anhydro-S-mercaptoadenosine 5’-phosphate (18) which can be desulphurised with Raney nickel to 2’-deoxyadenosine. A study 28 of the polynucleotide phosphorylase catalysed polymerisation of 8-substituted purine nucleoside diphosphates (obtained from the 8-bromonucleotides) showed that homopolymerisation did not occur. Copolymerisation with ADP and GDP was possible, although the rate and extent of the polymerisation decreased with increasing amounts of analogue diphosphate used in the polymerisation reaction. A simple enzymic synthesis of nucleoside 5’-phosphates 29 consists of the preparation of guanosine 3’ -+ 5’-linked dinucleoside phosphates from guanosine 2’,3’-cyclic phosphate using RNase TI followed by cleavage of the dinucleoside phosphate with snake venom phosphodiesterase. G>p+N

RNase T 6 GpN

where G > p 26

26 27 28 29

= guanosine

Snake venom + phospfiodiesterasc

G+pN

2’,3’-cycIic phosphate

M. Ikehara and S. Uesugi, Chem. and Pharm. BtdI. (Japan), 1969,17, 348; M. Ikehara, I. Tazawa, and T. Fukui, Chem. and Pharm. Bull. (Japan), 1969, 17, 1019. D. B. McCormick and G. E. Opar, J. Medicin. Chem., 1969, 12, 333. M. Ikehara and S. Uesugi, Tetrahedron Letters, 1970, 713. M. Tkehara, I. Tazawa, and T. Fukui, Biochemistry, 1969, 8, 736. A. Help and G. Kowollik, Coll. Czech. Chem. Comm., 1970,35, 1013.

Phosphates and Phosphonates of Biochemical Interest

125

Acrasin, the chemotactic agent which is responsible for aggregation of slime moulds, has been isolated and identified as adenosine 3’,5’-cyclic phosphate (19a).30 iso-Adenosine 3’,5’-cyclic phosphate (1 9b) has been prepared 31 by the action of butoxide on the 5’-(p-nitropheny1)ester 32 and its hormonal activity measured. The 3’-cyclic ester of 5’-deoxy-5’(dihydroxyphosphiny1methyl)adenosine (20) has been made 33 either by alkali 30 31

32

33

D. S. Barkley, Science, 1969, 165, 1133. G. Cehovic, I. Marcus, S. Vengadabady, and T. Posternak, Compt. rend. Sac. Phys. Hist. nat. Gentue, 1968, 3, 135 (Chem. A h . , 1969, 71, 81,688). R. K. Borden and N. Smith, J . Org. Chem., 1966, 31, 3247. G. H. Jones and J. G. Moffatt, U.S.P. 3,446,793 (Chem. Abs., 1969, 71, 70,903).

126

Organophosphorus Chemistry

treatment of a monoester 32 or by cyclisation with DCC;34it has similar pharmacological activity to (19a), but is less susceptible to hydrolysis. From a study of the equilibrium of the adenyl cyclase reaction it has been calculated 35 that the free energy of hydrolysis of (19a) is - 11-9kcal mol-1 at pH 7 and 25 "C,i.e. about 3 kcal mol-1 greater than the free energy of hydrolysis of ATP under comparable condition^.^^ The enthalpy of hydrolysis of (19a) to AMP has now been determined calorimetrically 37 as - 14.1 kcal mol-1 and hence it appears that the entropic contribution to the hydrolysis must be small. The enthalpy of hydrolysis of (19c) is smaller than that of (19a) but there is still a considerable release of energy during hydrolysis. The configuration at the 3'-position in (19a) was established by the degradation of the 0-methylated nucleotide with liquid hydrogen fluoride, the product being 2-O-rnethylribo~e.~~ Fluoride ion is a strong nucleophile for phosphoryl centres and hydrogen fluoride is a highly specific dephosphorylating agent for n u c l e ~ t i d e s .The ~ ~ reaction is dependent on temperature, time, and acid strength, and conditions have been described for the (a) R

=

adenosine

degradation of nucleotides to nucleosides or bases. Extended exposure to hydrogen fluoride appears to cause no deamination of adenine, guanine, or cytosine, and base analysis of RNA can be carried out with this reagent. From a study of n.m.r. data on the binding of cytidine 3'-phosphate to pancreatic RNase together with X-ray evidence concerning the structure 34

36

38

37

38 39

M. Smith, G. I. Drummond, and H. G . Khorana, J. Amer. Chem. SOC.,1961,83, 698. P. Greengard, 0. Hayaishi, and S. P. Colowick, Fed. Proc., 1969, 28, 467. R. A. Alberty, J. Chem. Educ., 1969,46, 713; R. A. Alberty, J. Biol. Chem., 1969, 244, 3290. P. Greengard, S. A. Rudolph, and J. M. Sturtevant, J . Biol. Chem., 1969, 244, 4798. D. Lipkin, W. H. Cook, and R. Markham, J . Amer. Chem. SOC.,1959, 81, 6198. D. Lipkin, B. E. Phillips, and J. W. Abrell, J . Org. Chem., 1969, 34, 1539.

Phosphates and Phosphonates 0f Biochemical Interest

127 of the enzyme, it has been suggested 40 that a ‘linear’ mechanism is more likely for RNase-catalysed hydrolysis reactions than a mechanism which involves the Pseudorotation Of a pentacovalent intermediate. Furthermore, it has been shown that during the enzymic hydrolysis of uridine 2’,3’-0cyclophosphorothioate,41a sulphur is not lost to the solvent.*lb This latter observation implies that pseudorotation of an intermediate pentacovalent adduct does not occur during the hydrolysis reaction. The rate of RNasecatalysed hydrolysis of uridine 2’,3’-cyclic phosphonate (20) is much lower than that for the hydrolysis of the corresponding phosphate. If pseudorotation occurs during the hydrolysis, one form of the pentacovalent intermediate requires a relatively electropositive methylene group to be in the apical position.4Z This would not be a favoured process43 and hence should have an adverse effect on the rate of hydrolysis. Kinetic measurement of the pancreatic RNase-catalysed hydrolysis of uridine 2‘,3‘-cyclic phosphate to uridine 3’-phosphate indicates that the mechanism is very similar to that for cytidine 2’,3’-cyclic phosphate.44 The degree of ionisation of the cytidine ring seems to be relatively unimportant in the latter case and the same ionisable groups on the enzyme are probably involved in both reactions. Temperature-jump studies show that two processes are involved in the interaction of pancreatic RNase and uridine 3’-ph0sphate,~~ an initial association of the enzyme and the nucleotide being followed by an isomerisation of the enzyme-nucleotide complex. At least three ionisable groups on the enzyme are involved and these results have been correlated with the known three-dimensional structure of the enzyme. Formycin (21) is an analogue of adenosine and its triphosphate can replace ATP in RNA polymerase Copolymers containing (21) can be prepared, e.g. poly(F-C) and poly(F-U), and these are susceptible to hydrolysis by pancreatic RNase giving rise to FpCp and FpUp respectively. These dinucleotides undergo further hydrolysis by the enzyme to the mononucleotides, The cyclic 2’,3’-phosphate of (21) is also unusual in undergoing enzymic hydrolysis by pancreatic R N ~ s ~ .It~ is’ difficult to see why phosphate esters of (21) are hydrolysed by this enzyme as the size and shape of the heterocyclic base are unlike those of a pyrimidine. How40

4l 42

43

44

a5 48

47

G . C. K. Roberts, E. A. Dennis, D. H. Meadows, J. S. Cohen, and 0.Jardetzky, Proc. Nnt. Acad. Sci. U.S.A., 1969, 62, 1151. W. Saenger and F. Eckstein, Angew. Chem. Internat. Edn, 1969, 8, 595; F. Eckstein, F.E.B.S. Letters, 1968, 2, 85. M.R. Harris, D. A. Usher, H. P. Albrecht, G, H. Jones, and J. G . Moffatt, Pruc. Nut. Acad. Sci. U.S.A., 1969, 63,246. F. H. Westheimer, Accounts Chem. Res., 1968, 1, 70; D. A. Usher, Proc. Nut. Acad. Sci. U.S.A., 1969, 62, 661. E. J. del Rosario and G. G. Hammes, Biochemistry, 1969, 8, 1884. G . G. Hamrnes and F. G. Walz jun., J . Amer. Chem. SOC.,1969, 91, 7179. M. Ikehara, K. Murao, F. Harada, and S. Nishimura, Biochim. Biophys. Acta, 1968, 355, 82; D. C . Ward, A. Cerami, E. Reich, G. Acs, and L. Altwerger, J. Biol. Chem., 1969, 244, 3243. M. Ikehara, K. Murao, and S. Nishimura, Biochim. Biophys. Acta, 1969, 182, 276.

128

Organophosphorus Chemistry

ever, the base does contain an ionisable NH group which is not present in either adenine or guanine and this may have a catalytic effect on the hydrolysis reaction. B. Nucleoside Po1yphosphates.-The synthesis of o~-~~P-Iabelled nucleoside di- and tri-phosphates has been 49 The most efficient method 49 consists of treating the S2P-labelledmonophosphates 6o with 2-cyanoethyl phosphorimidazolidate (22) or 2-cyanoethyl pyrophosphorimidazolidate (23) followed by base. The imidazolidates (22) and (23) can be obtained from the reaction between NN-carbonyldi-imidazole (24) and 0

+ N C ( C H , ) , OII P - N ~ N I \ / 0€1 HO

OH

0 0

NC (CH, ) ,O -PO P ''0 HO OH

HO

O€I

HO$O:2 0 0 !oyo?,B

I I OH OH HO

0 ll

O€I

8 II

N~N-P-O-P-OCH,CH,CN L f OH I 0I € 1

(23)

N~N-CO-N%

u

L f

(24)

2-cyanoethyl-phosphate or -pyrophosphate. It is claimed that the use of (22) and (23) is preferable to the use of (24) in con,junction with ortho- or pyro-phosphate.61 The latter method has been widely used in the past for 48 48

61

R. H. Symons, Biochim. Biophys. Acta, 1969, 190, 548. R. H. Symons, Biochim. Biophys. Acta, 1970, 209, 296. R. H. Symons, Biochem. Biophys. Res. Comm., 1966,24,872; R. H. Symons, Biochim. Biophys. Acta, 1968, 155. 609. D. E. Hoard and D. G. Ott, J . Amer. Chem. Soc., 1965, 87, 1785; D. G. Ott, V. N. Kerr, E. Hansbury, and F. N. Hayes, Analyt. Biochem., 1967, 21, 469.

Phosphates and Phosphonates of Biochemical Interest

129 the synthesis of nucleoside polyphosphates, e.g. 6-mercapto-9-fl-~-ribofuranosylpurine 5’4ripho~phate.~~ Adenosine 5’-bis(dihydroxyphosphinylmethy1)phosphinate (25) has been prepared 5 3 by treating 2’,3’-O-isopropylidene adenosine with the trimetaphosphate analogue of bis(dihydroxyphosphinylmethy1)phosphinic Since (25) contains no labile P-0-P bonds it would be interesting to investigate the inhibiting properties of this compound in enzymatic systems which require ATP as cofactor. Guanosine 5’-phosphohypophosphate (26)

HiC,

P

,CH,

/ \ 0 OH

0 0 0 II I1 II ROP-0-P-P-OH

I

HO

where R

I I HO O€I (26) =

guanosine

0

0

0

OH OH OH HO

OH

(25)

which is obtained from the exchange reaction between P1-guanosine-5’, P2-diphenyl pyrophosphate, and hypophosphoric is a strong competitive inhibitor of protein biosynthesis when used in place of GTP ;5s it permits the binding of fMet-tRNA to ribosomes, but is less effective than GTP. The determination of the three-dimensional structure of ATP as its hydrated sodium salt shows that two crystallographically independent forms of ATP are present, differing only in the orientation of the 5’-oxygen with respect to the ribose ring.57 In both forms the polyphosphate chain is folded back towards the purine base, in contrast to inorganic tripolyphosphate which exists in an extended form in the crystalline state. There also appears to be a difference between the conformations of the poly62

63 64 65 56

A. J. Murphy, J. A. Duke, and L. Stowring, Arch. Biochem. Biophys., 1970, 137, 297. D. B, Trowbridge and G . L. Kenyon, J . Amer. Chem. SOC.,1970,92, 2181. L. Maier, Helv. Chim. Acta, 1969, 52, 827. P. Remy, G. Dirheimer, and J. P. Ebel, Biochim. Biophys. Acta, 1967, 136, 99. P. Remy, M. L. Engel, G . Dirheimer, J. P. Ebel, and M. Revel, J . Mol. Biol., 1970, 48, 173.

57

0. Kennard, N. W. Isaacs, J. C. Coppola, A. J. Kirby, S. G . Warren, W. D . S. Motherwell, D. G . Watson, D. L. Wampler, D. H. Chenery, A. C. Larson, K. A. Kerr, and L. Riva di Sanseverino, Nature, 1970, 225, 333.

130

Organophosphorus Chemistry

phosphate chains in ATP and inorganic tripolyphosphate in solution 6 8 as the pH dependence of the spin-spin coupling in the 31Pn.m.r. spectra of ATP and ADP is different from that for linear tripolyph~sphate.~~

C. Oligo- and Poly-nuc1eotides.-The

most monumental feat in the field of polynucleotide chemistry during the past year has been the synthesis 6o of a gene for the principal alanine t-RNA in yeast. In essence, the synthesis consists of the exploitation of the ability of chemically synthesised oligodeoxynucleotides to form specific base-paired dimers and the linking of these dimers with T4 polynucleotide ligase. A total of seventeen segments, varying in chain length from penta- to icosa-nucleotides, were synthesised ZO 19 18 17 I6 I5 14 I3 I2 I I 10 9 8 7 6 5 4 3 2 1 G A U V C C G G A C U C G U C C A C C A -(4)I (1) -'c- T-A-A- G- G-C-C' 'T-G-AG- C- A- G-G-T-G-G-T'

1 1 1 1 1 1 T-1 C1 -G 1 -T,1 ,C1 -C-1 1 1 1 1

IC- C- G- G-A-F-

(3')RlOO (5') DEOXY

(3') DEOXY

50 49 48 47 4 6 45 44 4 3 42 41 40 39 38 37 36 35 34 33 32 31 30 29 28 27 26 25 24 23 22 21 20 19 18 17

Me2 - G C V C C C U U

Me

l

G

C

l

Y

G

G

G

A

G

A

G

H2 U C

V

C

C

G

G

T

Y

C

G

A

U

U

(35RRlBO

77 76 75 74 73 12 71 70 69 68 67 66 65 6 4 63 62 61 60 59 9 57 56 55 54 53 52 51 M 49 48 47 46

k?

Me

G G

G C G U G U G G 1 (4-)

Ic-C-C-G-C-A-C-A-C-C-G-c

C

G C G U A G U C ,-1 2 )(-, G-C-A-T-C-A-G-C-C--A

H2 G G V A

G C

M-2 G C G C

V

C

C-

(51) MOXY

T-C-G-C-G-C-G-A-G-G-

I I I I I I I T-G-G-C-G-C-G-T-A-G I I I I I I I l l l T-C-G-G-T-A-G-C-G-C t l l l l l l l l l

(35 DEOXY

G-G-G-C-G-T-G

-(l5)-

-(13)

(2hRlBO

y ( I Q > - a

n (I-

77 76 15 14 7 3 72 71 70 69 68 67 66 65 64 63 €2 61 80 59 58 57 56 55 54 %3 52 3 x) 49 48 47 46 Me

G G . -r

c-

G C G U G U G G C G C G V A (I41 G- C-A-TC- C- G- C- A- C-A- G-C-G-C

-

H2 H2 M.2 G U C G G U A G C G C G C U C (12') 1 (10') C- A-G-C-CA-T-C G- C- G-C-G-A-G-G-

-,

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

G-G-G-C-G-T-G I ( I 5 ) -

T-G-G-CG-C-G-T-AL-----(13)AL----(II)----J

G 7-C-G-G-T-A-G-C-

G-C-

C-

(3'1RleO

(5') M O X Y

(3) DEOXY

Totalplanfor the synthesis of a yeast alanine tRNA gene. The chemically synthesised segments are in brackets, the serial number of the segment being shown within the brackets. A total of seventeen segments (including 10 and 12) varying in chain length from penta- to icosa-nucleotides were synthesised. The assumption was made that the rare bases present in the tRNA arise by subsequent modification of the four standard bases used by the transcribing enzyme. Thus inosine is formed by deamination of adenosine and so comes from an A . T base-pair in D N A (Reproduced by permission from Nature, 1970, 227, 27) 68

65

eo

M. Ellenberger, L. Brehamet, M. Villeimin, and F. Toma, F.E.B.S. Letters, 1970, 8, 125. M. M. Crutchfield, C. F. Callis, R. R. Irani, and G. C. Roth, Znurg. Chem., 1962, 1, 813. K. L. Argarwal, H. Buchi, M. H. Caruthers, N. Gupta, H. G . Khorana, K. Kleppe, A. Kumar, E. Ohtsuka, U. L. Rajbhandary, J. H. van de Sande, V. Sgaramella, H. Weber, and T. Yamada, Nature, 1970, 227, 27.

Phosphates and Phosphonates of Biochemical Interest

131

by the general methods developed by Khorana's school in recent years.61 To simplify the task it was assumed that the atypical bases in the t-RNA arose by subsequent modification of the four standard bases used by the transcribing enzyme. Initial experiments suggest that DNA polymerase may be able to replicate the gene in the presence of suitable primers and that transcription of the appropriate strand to produce the t-RNAmay bepossible. Three deoxyribododecanucleotides of defined sequence have been synthesiseds2 by a method which doubled the chain length of the oligonucleotides at each condensation step. In this way, the products and reactants differ sufficiently in molecular weight to be separated by Sephadex gel filtration with appropriate exclusion limits. An advantage of this method of separation is that it is rapid, and the product emerges from the chromatographic column before the reactants. The oligonucleotides are related to the DNA sequence of the gene corresponding to bovine insulin Chain A. 4-Chloro-2-nitrophenol has been used 63 as a base-labile protecting group for phosphate groups in the synthesis of homodeoxyribo-oligonucleotides. The conditions required for its removal ( 2 sodium ~ hydroxide 100 "C/ 15 min), however, cause some deamination of adenine residues and four new base-labile protecting groups have been developed (27; R1 = C,H5), (27; R1 = 4-Me0.C,H4), (27; R1= PhCH,), and (2Q6* (27) and (28) are removed rapidly by 2~ sodium hydroxide at room temperature. Protecting groups (e.g. substituted acetals) which can be preferentially removed under carefully defined conditions have been successfully used in the synthesis of oligoribonucleotides.6s 0

II

ROP-OH I OH

(27) R = R1C0CH2CH2(28) R = PhCH=Nisoamyl nitrite

OBz

HO

where CBz Ba

64

65

OBz

7 O€I

=

N(4)-benzoylcytosine

H. G. Khorana, Pure Appl. Chem., 1968,17,313; Biochent. J., 1968,109, 709. S . A. Narang and S. K. Dheer, Biochemisiry, 1969, 8, 3443. S. A. Narang, 0. S. Bhanot, J . Goodchild, and R. H. Wightman, Chem. Comm., 1970, 91. S. A. Narang, 0. S. Bhanot, J. Goodchild, J. Michniewiez, R. Wightman, and S. K. Dheer, Chem. Comm.. 1970. 516. B. E. Griffin and C. B. Reese, Tetrahedron, 1969, 25, 4057.

132

Organophosphorus Chemistry

Aromatic phosphoramidates of protected nucleosides (29) can be degraded to the corresponding phosphates (30) by isoamyl nitrite without affecting other protecting groups,66 and this reaction has been used to prepare oligoribonucleotides of defined sequence.67 The 3’-end of an oligoribonucleotide can be protected during synthesis by a 2’,3’-cyclic phosphate group.6s Pancreatic RNase will cleave the cyclic phosphate to liberate the 3’-phosphate and phosphoryl migration can be prevented by acetylation of the 2’-hydroxy-group. Phosphorofluoridates can act as phosphorylating agents in the presence of strong base and have been used in a highly specific synthesis of oligodeoxyribonucleotides.70 No pyrophosphate formation occurs under these conditions, and dinucleoside phosphates can be obtained in high yield. This method should be particularly applicable to the synthesis of acidlabile phosphate esters. 3-4’(5’)-Imidazolyl propanoic acid (3 1) will catalyse the polymerisation of deoxyribonucleoside 5’-phosphates to give oligonucleotides,71 and although the mechanism of this reaction has not been studied it is probable

)P=O F

Merrifield resin

that nucleoside 5’-phosphorimidazolidates are intermediates. Adenosine and deoxyadenosine 5’-phosphorimidazolidates will participate in the template-directed synthesis of oligomers in the presence of a sterically ge

67

6g ‘O

E. Ohtsuka, K. Murao, M. Ubasawa, and M. Ikehara, J. Amer. Chem. SOC.,1970, 92, 3441. E. Ohtsuka, K. Murao, N. Ubasawa, and M. Ikehara, J. Amer. Chem. SOC.,1970, 92, 3445. T. Nejlson, Chem. Comm., 1969, 1139. R. Wittmann, Chem. Ber., 1963, 96, 771. R. G. von Tigerstrom and M. Smith, Science, 1970, 167, 1266. 0. Pongs and P. 0. P. Ts’o, Biochem. Biophys. Res. Comm., 1969, 36, 475,

Phosphates and Phosphonates of Biochemical Interest

133

suitable nucleoside Thus, a-adenosine and ara-adenosine are less effective substrates than /I-adenosine. Commercially available ‘Merrifield’ resin has been modified into a form which contains acyl chloride groups.73 This resin will esterify the 5‘hydroxy-group of thymidine which can then serve as a starting material for the synthesis of oligothymidylic acids. In the final step, the product can be removed from the resin by treatment with ammonia. The enzymic synthesis of a large number of oligo- and poly-nucleotides has been reported in the past year. Among the enzymes used have been ribonucleases (e.g. T, or N1),74-7a polynucleotide phosph~rylase,~~-~* and terminal nucleotidyl tran~ferase.~~f 86 The successful polymerisation of the 5’-pyrophosphates of atypical nucleosides can depend on the source of the polynucleotide phosphorylase 83 or on the substitution of manganese for magnesium in the medium.84 The ‘lag phase’ which has sometimes been observed 8 7 in the polymerisation of ADP with polynucleotide phosphorylase has been found to be of universal occurrence once care has been taken to remove contaminating oligo- and poly-nucleotides from the enzyme.aa It has been suggested that the lag is due to the enzyme having a more favourable conformation when it is bound to a primer, and hence the rate of enzymic synthesis is more rapid in the presence of a primer than in its absence. Venom exonuclease can be used to determine the chain length and the termini of oligonucleotides which have a 3’-phosphate group.89 Relatively large amounts of enzyme must be used and the reaction is slow, as the presence of a negatively charged group in the 3’-position of the oligomer has an adverse effect.g0 72 73 74 75

76

77

78

7g

83

84 85 86

89

H. Schneider-Bernloehr, R. Lohrmann, J. Sulston, L. E. Orgel, and H. Todd Miles, J . Mol. Biol., 1970, 47, 257. T. Kusama and H. Hayatsu, Chem. and Pharm. Bull. (Japan), 1970, 18, 319. J. Smrt, Coll. Czech. Chem. Comm., 1969, 34, 1702. T. Koike, T. Uchida, and F. Egami, Biochim. Biophys. Acta, 1969, 190, 257; S. Irie, T. Uchida, and F. Egami, Biochim. Biophys. Acta, 1970, 209, 289. M. Saito, Y. Furuichi, K. Takeishi, M. Yoshida, M. Yamasaki, K. Arima, H. Hayatsu, and T. Ukita, Biochim. Biophys. Acta, 1969, 195, 299. S. M. Zhenodarowa and M. I. Habarowa, Biochim. Biophys. Acta, 1969, 195, 1 ; S. M. Zhenodarowa and E. A. Sedelnikowa, Biochim. Biophys. Acta, 1969, 195, 8. S. K. Podder and I. Tinoco jun., Biochem. Biophys. Res. Comm., 1969, 34, 569. F. Pochon and A. M. Michelson, Biochim. Biophys. Acta, 1969, 182, 17. J. Simuth, K. H. Scheit, and E. M. Gottschalk, Biochim. Biophys. Acta, 1970, 204, 371. K. H. Scheit, Biochim. Biophys. Acta, 1970, 209, 445. F. Rottman and K. L. Johnson, Biochemistry, 1969, 8, 4354. M. Swierkowski and D. Shugar, Acta Biochim. Polon., 1969, 16, 263 (Chem. Abs., 1969, 71, 102,173). B. Zmudzka, C. Janion, and D. Shugar, Biochem. Biophvs. Res. Comm., 1969, 37, 895. B. Zmudzka, F. J. Bollum, and D. Shugar, J . Mol. Bior., 1969, 46, 169. B. Zmudzka, F. J. Bollum, and D. Shugar, Biochemistry, 1969, 8, 3049. T. Godefroy, M. Cohn, and M. Grunberg-Manago, European J. Biochem., 1970, 12, 236. F. R. Williams and M. Grunberg-Manago, Biochim. Biophys. Acta, 1964, 89, 66. M. Laskowski sen., Adv. Enzymol., 1967, 29, 165. G. M. Richards and M. Laskowski sen., Biochemistry, 1969, 8, 1786.

-

Organophosphorus Chemistry

134 N“pNB.. . . . .pN”p

Nu+n(pN) +pNwp

venom exonuclease

Not surprisingly, 2’,3’-dideoxyadenosine (32) 91 is lethal to E. coli as it blocks DNA synthesis irreversibly. The 5’-triphosphate of (32) is a competitive inhibitor of DNA polymerisation and, since it is incorporated into the end of polynucleotide chains, it terminates polymer synthesis.92

“

O

Y (32)

0 II NH20CCH2CH2S-P -OH I OH (33) 0

Y

0 II AdOP-SEt

II

> AdOP-OH I I OH OH D. Nucleoside Thiophosphates.-Nucleoside phosphorothioate monoesters and dinucleoside phosphate 5’-phosphorothioates have been obtained 93 from S-2-carbamoylethyl phosphorothioate (33) and a suitably protected nucleoside using DCC as condensing agent. The phosphorothioates are readily converted into phosphates on treatment with aqueous iodine.g4 Nucleoside 5’-S-ethyl phosphorothioates are hydrolysed by snake venom phosphodiesterase with the liberation of ethanethiol. H,O/OH-

0, ,OCH2CH,CN

O=P-0 -0’

*// P\

OH

(35)

-0’ (36)

When treated with dilute alkali, the 0-(2-cyanoethyl) esters of 5’-0tosyldeoxyribonucleoside 3’-phosphorothioates (34) cyclise to the corresponding 5’-S,3’-O-phosphorothiolates (35).96 On the other hand, B1

O2

B3 O4

O6

M. J. Robins, J. R. McCarthy jun., and R. K. Robins, Biochemistry, 1966, 5, 224; J. R. McCarthy jun., M. J. Robins, L. B. Townsend, and R. K. Robins, J. Amer, Chem. SOC.,1966, 88, 1549. L. Toji and S. S. Cohen, Proc. Nut. Acad. Sci. U.S.A., 1969, 63, 871. A. F. Cook, J. Amer. Chem. SOC.,1970, 92, 190. A. F. Cook, M. J. Holman, and A. L. Nussbaum, J. Amer. Chem. SOC.,1969,91,6479. J. Nagyvary, S. Chladek, and J. Roe, Biochem. Biophys. Res. Comm., 1970, 39, 878.

135

Phosphates and Phosphonates of Biochemical Interest

polymerisation occurs on warming a solution of (34) in dimethylformamide. Adenosine 3’,5’-O-cyclic phosphorothioate (36) has a lipolytic activity similar to that of the 3’,5’-cyclic phosphateg6but is not a substrate or inhibitor of 3’,5’-cyclic nucleotide phosphodiesterases, and hence could be of pharmacological importance. U.V. and 0.r.d. measurements show that analogues of IMP with P-N and P-S bonds, e.g. (37; X = 0, Y = S), (37; X = S, Y = 0),and (37; X = NH, Y = 0) have the same conformation in aqueous solution as native IMP.97 The analogues are substrates of the IMP-dehydrogenase from Aerobacter aerogenes and kinetic measurements indicate that they bind to the dehydrogenase as dianions. Details have been published g8 for the enzymic synthesis of polyribonucleotides which contain a phosphorothioate backbone. DNA-dependent RNA polymerase can utilise either or both uridine and adenosine 5 ’ 4 (1-thiotriphosphate) [(ppp,-U) or (ppp,-A)] in the presence of a poly d(A-T) template. The rate and extent of the reaction are reduced, however, and are least when both (ppp,-U) and (ppp,-A) are present as substrates. Unlike ATP and UTP, (ppp,-A) and (ppp,-U) can exist in two diastereoisomeric forms (38a and b), and as synthesised each should contain approxi-

Ho-f Y

OEI

,0-CH2-

0,

..p

HS’

“’0-P

P-

(38a)

mately equal amounts of the two isomers. If one diastereoisomer is a very poor substrate for the RNA-polymerase, this might explain the reduced efficiency of the polymerisation reaction. The introduction of a phosphorothioate backbone into polynucleotides has little effect on their physical stability but does reduce their susceptibility to hydrolysis by nucleases. This type of polyribonucleotide is a good inducer of interferon. Treatment of cells with poly(AS-US), the polymer derived from poly(A-U) with a phosphorothioate backbone, can lead to a significant increase in their resistance to infe~ti0n.O~ g6

97 88 99

F. Eckstein and H. P. Bar, Biochim. Biophys. Acta, 1969, 191, 316. A. Hampton, L. W. Brox, and M. Bayer, Biochemistry, 1969, 8, 2303. F. Eckstein and H. Gindl, European J . Biochem., 1970, 13, 558. E. De Clercq, F. Eckstein, and T. C. Merigan, Science, 1969, 165, 1137; E. De Clercq, F. Eckstein, H. Sternbach, and T. C. Merigan, Virology, 1970, 42, 421.

136

Organophosphorus Chemistry

(ppp,-A) has been incorporated into the 3'-end of yeast phenylalanine t-RNA.loO The modified t-RNA could be charged with phenylalanine by aminoacyl t-RNA synthetase and was more resistant to hydrolysis by snake venom phosphodiesterase than the native t-RNA. (ppp,-A) was not a substitute for ATP in the activation of phenylalanine by aminoacyl t-RNA synthetase, but acted as a competitive inhibitor. E. Physical Methods and Analytical Techniques.-The conformations and steric structures of nucleotides and derivatives have been the subject of a recent review.lol The evidence discussed in the review had been derived mainly by X-ray crystallographic techniques for compounds in the solid state; however, 31P n.m.r. spectroscopy can be used to deduce the most favourable conformation adopted by dinucleoside phosphates in aqueous so1ution.lo2 The chromatographic separation on thin layers of DEAE-cellulose of 32P-labelledoligonucleotides up to 50 residues long has been described.lo3 This is a detailed discussion of the combined techniques of electrophoresis and homochromatography, which have been used with such success by Sanger in the determination of the base sequence of 5S-RNA.l0* Polyribonucleotides can be attached to cellulose using DCC as condensing agent. The cellulose-bound polymer can then be degraded in a stepwise fashion from the 3'-end by treatment with periodate and cyclohexylamine followed by alkaline phosphatase.lo6 The characterisation of nucleosides and nucleotides by pyrolysis g.l.c.106~ lo' is an interesting method of analysing trace quantities of material. Pyrolysis of the nucleoside or nucleotide at 800 "C followed by gas chromatography of the decomposition products gives rise to reproducible, unique patterns for each compound. The mass spectrometric analysis of trimethylsilyl derivatives of dinucleotide phenyl boronates has been used to determine their base sequence.lo8 This method appears to give better results than the mass spectrometric analysis of trimethylsilyl dinucleotides,logand should be applicable to the determination of the base sequence in short oligonucleotides. E. Schlimme, F. von der Haar, F. Eckstein, and F. Cramer, European J . Biochem. 1970, 14, 351. lol N. N. Preobrazhenskaya and Z . A. Shabarova, Rum. Chem. Reu., 1969, 38, 111. lo2 M. Tsuboi, S. Takahashi, Y. Kyogoku, H. Hayatsu, T. Ukita, and M. Kainosho Science, 1969, 166, 1505. loS G. G. Brownlee and F. Sanger, European J. Biochem., 1969, 11, 395. loo G. G. Brownlee, F. Sanger, and B. G. Barrell, J. Mol. Biol., 1968, 34, 379. lo5 T.fE. Wagner, H. G. Chai, and A. S. Warfield, J. Amer. Chem. Soc., 1969, 91, 2388. lo8 C. B. Honaker and A. D. Horton, J . Gas Chromatog., 1965, 3, 396. lo' L. P. Turner, AnQlyt. Biochem., 1969, 28, 288. lo8 J. J. Dolhun and J. L. Wiebers, J. Amer. Chem. Soc., 1969, 91, 7755. Io9 D. F. Hunt, C . Hignite, and K. Biemann, Biochem. Biophys. Res. Comm., 1968, 33, 378. loo

137

Phosphates and Phosphonates of Biochemical Interest

2 Coenzymes and Cofactors A. Phosphoenol Pyruvate.-In aqueous solution the hydrolyses of dibenzyl (39) and monobenzyl (40) esters of phosphoenol pyruvic acid proceed by the stepwise loss of benzyl alcohol.llo In the presence of hydroxylamine in aqueous solutions, (39) breaks down to dibenzyl phosphoric acid and

HO’

c

‘COOP(0)(OCH,Ph)2

I1 CH,CO.COOP(O)(OCH,Ph)2

(43) (42)

I

+ PhCH20H

NH,OH/H,O

CH,CCOOH

It

NOH

+ (PhCH@)zP(O)(OH)

(44)

pyruvic acid hydroxamate (41), while (40) gives (41) and benzyl alcohol under the same conditions. The hydrolysis of (39) probably proceeds with the intramolecular formation of a pentacovalent phosphorane, which can react further to give either the cyclic anhydride (42),ll1 or the linear anhydride (43). Hydrolysis of (42) gives (40) which can again form an intramolecular phosphorane. The latter then decomposes to benzyl alcohol and the mixed anhydride of pyruvic and phosphoric acids. The anhydride (43) will react with hydroxylamine with the formation of (41). The cyclic phosphate (44) from ethyl 2-hydroxy-cinnamic acid hydrolyses with C - 0 bond fission; however, the precise mechanism of hydrolysis has not yet been determined.l12 110 111

112

S. J. Benkovic and K. J. Schray, J. Amer. Chem. SOC.,1969, 91, 5653. V. M. Clark and A. J. Kirby, J. Amer. Chem. SOC.,1963, 85, 3705. J. F. Marecek and D. L. Griffith, J. Amer. Chern. SOC.,1970, 92, 917.

138

Organophosphorus Chemistry

Alkyl homologues of PEP can be prepared113 by the Perkow reaction, but the introduction of a bulky group into the PEP molecule reduces the efficiencyof its reaction with pyruvate kinase. This suggests that the binding of PEP might take place at a critically defined site on the ternary enzyme complex 114and that the homologues are too bulky to bind properly at this site. The enzymic carboxylations of PEP by PEP-carboxylase, PEP-carboxykinase, and PEP-carboxytransphosphorylase take place with the addition of carbon dioxide to the same side of the enzyme-bound PEP.l15 This has been taken to indicate that the three enzymes may have a common genetic link.

B. Nicotinamide Coenzymes.-Several NAD+ analogues have been synthesised recently and studied as substrates of oxidoreductases.116-118The reduced form of the analogue containing 4-thio-~-ribose(45) 116 is more fluorescent than native NADH, probably because the molecule assumes an anti-conformation, a view which has been supported by 0.r.d. evidence. The analogue which contains 2,3-dideoxyribose attached to the nicotinamide moiety (46) 117 has fluorescence and absorption spectra which are similar to NAD+ and reacts very slowly with liver alcohol dehydrogenase. Hence the binding of the coenzyme to the molecule must be affected by the presence of the two hydroxy-groups on the ribose ring. Reduction of NAD+ with borohydride leads to a mixture of 1,4- and 1,6-NADH (47) together with the tetrahydro-compo~nd.~~~ Like 1,4NADH, (47) has a maximum in its U.V. spectrum near 345 nm and can be degraded to a derivative with an U.V. maximum at 290 nm. This derivative can be cleaved enzymically to AMP and hence the chromophore must be altered in the nicotinamide rather than the adenine residue.120 It is probable that hydration across the 4,Mouble bond of the nicotinamide ring (48) would account for the change in the absorption spectrum of (47). A similar hydration across the 5,6-double bond of 1,4-NADH (49) has been postulated to account for the change in its absorption spectrum on treatment with acid.121 A pyridine nucleotide, ADP-ribosyl-NAD+, which has been isolated from A . vinelandii 122 may be a precursor of poly-adenosine diphosphate 113

114

116 117 11* 119

121 122

A. E.Woods, J. M. O’Bryan, P. T. K. Mui, and R. D. Crowder, Biochemistry, 1970, 9, 2334. A. S. Mildavan and M. Cohn, J. Biol. Chem., 1966, 241, 1178. I. A. Rose, E. L. O’Connell, P. Noce, M. F. Utter, H. G. Wood, J. M. Willard, T. G . Cooper, and M. Benziman, J. Biol. Chem., 1969, 244, 6130. D.J. Hoffman and R. L. Whistler, Biochemistry, 1970, 9, 2367. C. Woenckhaus and R. Jeck, Annalen, 1970,736, 126. J. F. Biellmann and M. J. Jung, F.E.B.S. Letters, 1970, 7 , 199. S. Chaykin and L. Meissner, Biochem. Biophys. Res. Comm., 1964, 14, 233. K . Chakraverty, L. King, J. G . Watson, and S. Chaykin, J. Biol. Chem., 1969, 244, 4208. R. Segal and G. Stein, J. Chenz. SOC.,1960, 5254; A. G. Anderson and G. Berkelhammer, J. Amer. Chem. SOC.,1958, 80, 992. T. Imai, S. Okuda, and S. Suzuki, J. Biol. Chem., 1969, 244, 4547.

Phosphates and Phosphonates of Biochemical Interest

139

0""""

OCONH2

dN+ Rod

RO

HO

(46)

OH

(45)

HJ3foNH2

Roe H

(47)

(49)

where R

=

Adenosine 5'-pyrophosphoryl

r i b 0 ~ e . lNothing ~~ is known concerning the biological function of this unusual polymer or of the pyridine nucleotide. C. Nucleoside Diphosphate Sugars.-The structure, biosynthesis, and funcand the biosynthesis of polysaccharides 125 have tion of teichoic been the subjects of recent reviews. The number of nucleoside diphosphate sugars which have been discovered and characterised continues to grow lZ3

lZ4

lZ5

T. Shima, S. Hasegawa, S. Fujimura, H. Matsubara, and T. Sugimura, J. Biol. Chem., 1969, 244, 6632; P. Chambon, J. D. Weill, J. Doly, M. T. Strosser, and P. Mandel, Biochem. Biophys. Res. Comm., 1966,25, 638. J. Baddiley, Accounts Chem. Res., 1970, 3, 89. W. Z . Hassid, Science, 1969, 165, 137.

140

Organophosphorus Chemistry

r a ~ i d l y . l ~ ~In - l ~addition ~ to the syntheses of GDP-rhamnose 132 and UDP-galact~samine,~~~ the synthesis of an analogue of UDPGlc derived from 5'-deoxyuridine 5'-pyrophosphonic acid (50) has been achieved.134 00 HO OH

UDPGlc-dehydrogenase will oxidise (50) at the 6-position of the glucose residue and models indicate that the environments round this position in (50) and UDPGlc are very similar. The stereochemistry of the two molecules in the region of the pyrophosphate bridge is dissimilar, however, and pyrophosphatases which cleave UDPGlc do not react with (50). UDP-N-acetylglucosamine 2-epimerase catalyses the conversion of UDPGlcNAc into ManNAc (51) and UDP.136 This reaction is unusual as (51) is released as the free sugar and not as a phosphate or pyrophosphate ester. It is suggested136that the epimerisation of the GlcNAc takes place while the sugar is bound to the enzyme. Oxidation by NAD+ of the 3-hydroxy-group of the enzyme-bound GlcNAc (52), followed by enolisation (53) and reprotonation, can lead to epimerisation of the N-acetyl group to give (54). Reduction of (54) by NADH followed by cleavage of the enzyme-sugar bond liberates (51). The enzyme system in parsley which degrades UDP-glucuronic acid to UDP-pentoses is another which requires NAD+ as c ~ f a c t o r . UDP~~~ apiose (55) is one product of this reaction together with UDP-arabinose and UDP-xylose. Lipids have recently been implicated in saccharide biosynthesis and polyprenol phosphate sugars have been isolated from a number of N. K. Kochetkov, E. I. Budowsky, T. N. Druzhinina, N. D. Gabrieljan, I. V. KomIev, Yu. Yu. Kusov, and V. N. Shibaev, Carbohydrate Res., 1969, 10, 152. N. K. Kochetkov, E. I. Bucovskii, V. N. Shibaev, and Y. Y . KUSOV,Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 1136 (Chem. Abs., 1969, 71, 70,870). 12* A. Garcia Trejo, G . J . F. Chittenden, J. G. Buchanan, and J. Baddiley, Biochem. J . , 1970,117, 637. n9 I. Das, M. A. Wentworth, H. Ide, H. G . Sie, and W. H. Fishman, Biochim. Biophys. Acta, 1970, 201, 375. lao P. Biely and R. W. Jeanloz, J . Biol. Chem., 1969, 244, 4929. lax A. Kobata and V. Ginsburg, J. Biol. Chem., 1970, 245, 1484. la2 G. A. Barber, Biochemistry, 1969, 8, 3692. 133 F. Maley, Biochem. Biophys. Res. Comm., 1970, 39, 371. la* P. C. Bax, F. Morris, and D. H. Rammler, Biochim. Biophys. Acta, 1970, 201, 416. lS5 C. E. Cardini and L. F. Leloir, J. Biol. Chem., 1957, 225, 317; D. G. Comb and S. Roseman, Biochim. Biophys. Acta, 1958, 29, 653. 136 W. L. Salo and H. G. Fletcher jun., Biochemistry, 1970, 9, 882. 13' H. Sandermann jun. and H. Grisebach, Biochim. Biophys. Actn, 1970, 208, 173. 126 12'

Phosphates and Phosphonates of Biochemical Interest UDPGlcNAc

141

+

NHAC (52)

NADH

NADH3

CH,OH Ok

+H+ P

-H+

HO 0

NHAc

-0

____j

HO 0 (54)

NHAc

Organophosphorus Chemistry

142

s o ~ r c e s . ~ ~In* particular, -~~~ an enzyme has been foundl*l in liver which catalyses the transfer of glucose from UDPGlc to dolichol phosphate (56)142and then to a protein. Since dolichol phosphate glucose rapidly breaks down to a 1,6-anhydroglucosan (57) on treatment with alkali, the glucose could be joined to the phosphoryl group with a p-glycosidic linkage.

where R = uridine 5’-pyrophosphoryl

-

UDPGlc + lipid Glc-lipid +protein Glc-protein

-

Glc-lipid + U DP Glc-protein + lipid Glc + protein

---+

0

II

H [CH2C(Me)=CCH,],,CH,CH(Me)CHzCH20POR

I

OH (57) D. Other Nucleotide Coenzymes.-Coenzyme A analogues in which the adenine residue has been replaced by guanine or hypoxanthine have been synthesised 143 by a modification of the phosphoromorpholidate method 138

139

140

141 149

143

A. Wright, M. Denkert, P. Fennessey, and P. W. Robbins, Proc. Nat. Acad. Sci. U.S.A., 1967, 57, 1798. Y . Higashi, J. L. Strominger, and C. C. SweeIey, Proc. Nat. Acad. Sci. U.S.A., 1967, 57, 1878. M. Scher, W. J. Lennartz, and C. C. Sweeley, Proc. Nat. Acad. Sci. U.S.A., 1968, 59, 1313. N. H. Behrens and L. F. Leloir, Proc. Nat. Acad. Sci. U.S.A., 1970, 66, 153. J. Burgos, F. W. Hemming, J. F. Pennock, and R. A. Morton, Biochem. J., 1963, 88, 470. M. Shimizu, 0. Nagase, S. Okada, and Y. Hosokawa, Chem and Pharm. Bull. (Japan), 1970, 18, 313.

Phosphates and Phosphonates of Biochemical Interest

143

A ~conventional synthesis used in the first successful synthesis of C O A . ~ ~ of D-pantothenic acid 4’-phosphate using dibenzyl phosphorochloridate has been pub1i~hed.l~~ 3 Naturally Occurring Phosphonic Acids A. Aminophosphonic Acids.-A study of the uptake of 14C-labelled2-aminoethylphosphonic acid (58) and 2-aminophosphonopropionicacid (59) by Tetrahymena pyriformis has shown 146 that while ( 5 8 ) is incorporated into the phospholipid fraction of the protozoon without degradation, (59) is incorporated as (58). No radioactivity due to (59) could be detected in the phospholipids of Tetrahymena which suggests either that decarboxylation occurs before incorporation or that the decarboxylation of lipid-bound (59) is an extremely efficient process. NH,CHCH,P(O)(OH),

- co2

I

NH,CH,CH,P(O)(OH), (58)

COOH (59)

OH

(ONOH), (60)

Aminophosphonic acids and related compounds can be made volatile by trimethylsilylation and so can be analysed by a combination of g.1.c. and mass This should be useful for the characterisation of trace amounts of phosphoro- and phosphono-lipids which occur in protozoa and in marine organisms. The isolation 14*and synthesis 149-151 of a number of phosphonolipids have been reported during the past year. In particular, ~-2,3-dihydroxypropylphosphonic acid (60) an analogue of L-glycerol-lphosphate has been prepared by an Arbusov reaction on 2,3-0-isoNo mention has been made of the propylidene 34odopropylene glyc01.l~~ stability of (60) and 2-hydroxyphosphonic acids are unstable in aqueous solutions near ne~tra1ity.l~~ Carboxylic esters of 2-hydroxyphosphonic acids are, however, relatively stable under these conditions 154 which should enable phosphonolipids derived from (60) to be prepared and studied. 144 145

J. G. Moffatt and H. G. Khorana, J. Amer. Chem. SOC.,1961, 83, 663. M. Yoshioka, K. Samejima, and Z. Tamura, Chem. and Pharm. Bull. (Japan), 1969, 17, 1265.

148 14’ 148

149

15* 151 152

15s 154

J. D. Smith and J. H. Law, Biochemistry, 1970, 9 , 2152. K. A. Karlsson, Biochem. Biophys. Res. Comm., 1970, 39, 847. T. Hori, M. Sugita, and 0. Itsaka, J , Biochem. (Japan), 1969, 65, 451. E. Baer and K. V. J. Rao, Canad. J. Biochem., 1970, 48, 184. E. Baer and S. K. Pavanaram, Canad. J. Biochem., 1970,48,221. E. Baer and G. R. Sarma, Canad. J. Biochem., 1969,47, 603. E. Baer and H. Basu, Canad. J. Biochem., 1969, 47, 955. W. Vogt, Tetrahedron Letters, 1970, 1281. B. D. Place. Ph.D. Thesis, University of Warwick, 1969.

1 44

Organophosphorus Chemistry

B. Phosphonomycin.-A new broad-spectrum antibiotic, phosphonomycin, . ~ ~antibiotic, ~ which can has been isolated from Streptomyces f r ~ d i a e The be administered orally, attacks the cell walls of bacteria but shows little toxicity to the host. The structure of phosphonomycin has been shown to be (- )-(1 R, 2S)-1,2-epoxypropylphosphonicacid (61) l S 6by a combination

Me0 H-j+ Me

H P (0)(0Me) 2 OMe

/

Ag,O/MeI

MeC = CMgBr + ClP(O)(OBu),

-

MeC s CP(O)(OBu),

I..

H,/Lindlar catalyst

(a) HCI

(61)

' (b) Hzo2

Me

P(O)(OBu),

111 MeCH2CH0 166

166

D. Hendlin, E. 0. Stapley, M. Jackson, H. Wallick, A. K. Miller, F. J. Wolf, T. W. Miller, L. Chaiet, F. M. Kahan, E. L. Foltz, H. B. Woodruff, J. M. Mata, S. Hernandez, and S. Mochales, Science, 1969, 166, 122. B. G. Christensen, W. J. Leanza, T. R. Beattie, A. A. Patchett, B. H. Arison, R. E. Ormond, F. A. Kueld jun., G . Albers-Schonberg, and 0. Jardetsky, Science, 1969, 166, 123.

Phosphates and Phosphonates of Biochemical Interest

145 of spectroscopic techniques and by degradation to dimethyl threo-l,2dimethoxypropylphosphonate(62). Final confirmation of the structure of (61) was provided by its synthesis from propynylmagnesium bromide and di-n-butyl phosphorochloridate. Additional evidence for the cis-relationship of the methyl and phosphonyl groups came from the nuclear Overhauser effect which was observed for the methyl protons on irradiation of the phosphorus nucleus. Phosphonomycin reacts irreversibly with pyruvate-UDPGlcNAc transferase of bacteria 155 possibly by the formation of a covalent bond between the active site of the enzyme and the epoxide function. Phosphonomycin might be expected to react with a variety of possible active sites of enzymes because in addition to being a water-soluble epoxide it is also a P-XYZ phosphorylating agent.167 4 Oxidative Phosphorylation One weakness of the chemical theory of mitochondria1 oxidative phosphorylation is that in spite of intensive efforts, no ‘energy rich’ intermediates have yet been isolated. This failure could be either because the intermediates do not exist 158 or because they break down during isolation. The production of ATP by the aerobic oxidation of di-imidazolylferrohaemochrome in solution in NN-dimethylacetamide containing imidazole, orthophosphate, and ADP lKS has led to the suggestion that phosphorylated imidazole derivatives may be involved in respiratory oxidative phosphorylation.160 Oxidation of a cytochrome held in a position close to a phospholipid or phosphoprotein could lead first to an unstable phosphorylated imidazole radical and then to an N-phosphorylated imidazole. The latter could react with orthophosphate to give a phosphoric anhydride (63) which in turn could convert ADP into ATP. According to this theory, inhibitors of electron transport would form complexes with electron carriers and hence prevent electron transport, while uncouplers would react with the radical precursor of N-phosphoryl imidazole and so prevent phosphoryl transfer.

where ROH 16‘

15* 169

le0

= phospholipid

or phosphoprotein

V. M. Clark and D. W. Hutchinson, Prugr. Org. Chem., 1968, 7 , 75. P. Mitchell, Nature, 1961, 191, 144. W. S. Brinigat, D. B. Knaff,and J. H. Wang, Biochemistry, 1967,6, 3 6 ; T. A. Cooper, W. S. Brinigar, and J. H. Wang, J. Biol. Chem., 1968, 243, 5854. J. H. Wang, Accounts Chem. Res., 1970, 3, 90; J. H. Wang. Science, 1970, 167, 25.

146

Organophosphorus Chemistry

Other systems which have been proposed as models for oxidative phosphorylation are acylated hydroquinones (64) 161*le2 and thioethers For example, such as (65), (66), or 5'-deo~y-5'-methylthioadenosine.~~~ ATP has been formed by the bromine oxidation of a solution of AMP, (65), and orthophosphate in pyridine, when the products include the sulphoxide of (65). This suggests that a sulphonium intermediate (67) may be formed initially between (65) and a bromonium ion. Interaction of (67) with phosphate followed by phosphoryl transfer to ADP leads to ATP and the sulphoxide. Haemin has been used in place of bromine in the oxidative synthesis of ATP from ADP, orthophosphate, and either tocopherol or thioglycollic acid.l**

fY

MeSCH,CH,CHCOOH I NHAc

HO

RSR

+ Brf

R ___+

\

R$R

%

I

Br

ATP

R-S-O-P< / Br

n W 0 II OH OH

+ Br- + RoSO

5 Sugar Phosphates A. Pentoses.-/bRibofuranose 1-phosphate (68) is the only sugar phosphate which is formed in the reaction between D-ribose, orthophosphate, and cyanogen or cyanamide.ls5 This method has been used to prepare l80-label1ed(68) le6and since it has been found that the oxygen atom of the P-0-C bond was derived mainly from the ribose, the phosphorylating agent must be an imidoyl phosphate derived from the addition of orthophosphate to cyanogen.le7 Ribose 5-phosphate 1-methylenediphosphonate(69) has been isolated 168 V. M. Clark, M. R. Eraut, and D. W. Hutchinson, J . Chem. SOC.(C), 1969, 79. T. Wieland and H. Aquila, Chem. Ber., 1969, 102, 2285. le3 D. 0. Lambeth and H. A, Lardy, Biochemistry, 1969, 8, 3395. 16* E. Bauerlein and T. Wieland, Chem. Ber., 1970, 103, 648. le6 M. Halmann, R. A. Sanchez, and L. E. Orgel, J. Org. Chem., 1969,34, 3702. lS6 M. Halmann and H. L. Schmidt, J . Chem. SOC.(C), 1970, 1191. 18' R. Lohrmann and L. E. Orgel, Science, 1968, 160, 64. 16* A. W. Murray, P. C. L. Wong, and B. Friedrichs, Biochem. J., 1969, 112, 741. 161

lsa

147

Phosphates and Phosphonates of Biochemical Interest -*

'

Y

o

HO

2

0

H o y ~ ~ o P ~ o ~ ~ o H ~

+ H,POj + (CN)2

H

OH

HO

OH (68)

(69) from the reaction between ribose 5-phosphate and 5'-adenylyl methylenediphosphonate 16u which is catalysed by 5-phosphoribosyl pyrophosphate synthetase from Ehrlich ascites-tumour cells. The isolation of (69) is direct confirmation that the reaction proceeds with a one-step pyrophosphate transfer 170 rather than with two consecutive phosphate transfers. Ribose 5-phosphorothioate, which can be prepared by the action of thiophosphoryl chloride on ribose, is also a substrate for the pyrophosphate synthetase.lsU B. Hexoses.-/h-Glucopyranose 1-phosphate (70) has been prepared by addition of dibenzyl phosphoric acid to 3,4,6-tri-O-acetyl-l ,Zanhydro-aCH,OH (a) (PhCH,O),P(O)(OH),

(b) removal of protecting groups

(71) CH,OAc

OCCI,

II

0

OCOCCI,

(73) 170

T. C. Myers, K. Nakamura, and J. W. Flesher, J . Amer. Chem. SOC.,1963, 85, 3292. H. G. Khorana, J. F. Fernandes, and A. Kornberg, J. Bid. Chem., 1958, 230, 941.

148

Organophosphorus Chemistry

D-glucose (71) followed by the removal of protecting groups.171 The fully protected a-anomer (73) of (70) has been obtained172 by treatchloride (72) ing 3,4,6-tr~-O-acetyl-2-O-(tr~ch~oracetyl)-~-~-glucopyranosyl with silver dibenzyl phosphate. Neighbouring group participation by the trichloracetyl group in the 2-position does not appear to affect the steric course of this reaction, and migration of the phosphoryl group is prevented if the benzyl groups are removed before the ester groups from the fully protected sugar phosphate. The stereospecific formation of D-glucose 6-phosphate (74) from D-fructose 6-phosphate catalysed by phosphoglucose isomerase has been studied by lH n.m.r. and it has been shown that the transformation occurs by a combination of C-2 proton exchange with solvent and hydride transfer from C-1 of the ketose to C-2 of the aldose. A study of the mechanism of phosphoribose isomerase by this technique was not so successful, as the n.m.r. spectrum of D-ribofuranose 5-phosphate is complex and only the signals due to C-2 protons are readily distinguishable.

OH (74)

The coupled reduction of NADP+ by (74) which is catalysed by glucose 6-phosphate dehydrogenase174 has been used to follow the very rapid mutarotation of (74). The enzyme is specific for the p-anomer and the rate of mutarotation of (74) is 240 times faster than that for a-D-glucose measured polarimetrically under the same conditions. The accelerated rate of mutarotation is probably due to intramolecular catalysis by the phosphate group in (74). The mass spectrometric behaviour of volatile trimethylsilyl sugar phosphates175 has been described in detail and a summary of the ions which are of particular use in their identification has been 6 Inositol Phosphates and Phospholipids A. Inositol Phosphates.-Reviews have recently appeared on inositol phosphates 17' and p h o s p h a t i d e ~ . ~Quebrachitol ~~ (1-~-2-O-methyl-chiro171 17a

173 174

17L 178

177

178

C. L. Stevens and R. E. Harmon, Carbohydrate Res., 1969, 11, 99. C. L. Stevens and R. E. Harmon, Carbohydrate Res., 1969, 11, 93. M. S. Feather and M. J. Lybyer, Biochem. Biophys. Res. Comm., 1969, 35, 538. J. M. Bailey, P. H. Fishman, and P. G. Pentcher, Biochemistry, 1970, 9, 1189. F. Eisenbert jun. and A. H. Bolden, Analyt. Biochem., 1969, 29, 343. M. Zinbo and W. R. Sherman, J . Amer. Chem. SOC.,1970, 92, 2105. S. J. Angyal, B. M. Luttrell, A. F. Russell, and D. Rutherford, Ann. N . Y. Acad. Sci., 1969, 165, 533. B. A. Klyashchitskii, S. D. Sokolov, and V. I. Shvets, Russ. Chem. Rev., 1969,38, 345.

<:sH+ -

149

Phosphates and Phosphonates of Biochemical Interest

-+

HO

OH

(75)

f

OH

(76)

OH


HO

OH (77)

&dLH

HO

ors

(a) (b) (PhO)2P(0)CI removal of protecting groups

OCOPh PhCOO q r hPhCOO COPh OOCPh

(78)

inositol) (75) has been used as a starting material in the synthesis of 1-L-myo-inositol phosphate (76). Conversion of (75) into 1-L-1-0-tosylchiro-inositol (77) was followed by benzoylation and hydrolytic cleavage of the tosyl group. Neighbouring group participation by a benzoyl group occurred during the hydrolysis and the inverted product 1-~-1,2,4,5,6penta-0-benzoyl-myo-inositol (78) was obtained. Phosphorylation of (78) with diphenyl phosphorochloridate and removal of the protecting groups gave (76).179 syn-myo-Inositol 1-phosphate 180 and its 1,2-dipalmitoylsyn-glycerol derivative l8l$lS2 have been prepared by similar methods. B. Phospholipids.-2,4,6-Tri-isopropylbenzenesulphonyl chloride will effect the esterification of 1,2-diacyl-syn-glycerol 3-phosphoric acids la3 (79) in high yield and with little pyrophosphate formation.184 This route is, therefore, an improvement on the standard method which involves phosphorochloridates.186 Naturally occurring N-acylphosphatidyl ethanolamines la6 are esters of D. Mercier, J. E. G. Barnett, and S. D. Gero, Tetrahedron, 1969, 25, 5681. B. A. Klyashchitskii, V. V. Pimenova, V. I. Shvets, S. D. Sokolov, and N. A. Preobrazhenskii, Zhur. obshchei Khim., 1969, 39, 2373 (Chem. Abs., 1970, 72, 55,793). 181 B. A. Klyashchitskii, E. G. Zhelvakova, V. I. Shvets, R. P. Evstingneeva, and N. A. Preobrazhenskii, Tetrahedron Letters, 1970, 587. P. A. Gent, R. Gigg, and C. D. Warren, Tetrahedron Letters, 1970, 2575. 18* Y. Lapidot, I. Barzilay, and J. Hajdu, Chem. and Phys. Lipids, 1969, 3, 125 (Chem. A h . , 1969, 71, 51,486). 184 R. Aneja, J. S. Chadha, and A. P. Davies, Tetrahedron Letters, 1969, 4183. lBS J. S. Chen and P. G. Barton, Canad. J . Biochem., 1970, 48, 585. R. M. C. Dawson, N. Clarke, and R. H. Quarles, Biochem. J., 1969, 114, 265; R. Bomstein, Biochem. Biophys. Res. Comm., 1965, 21, 49; H. Debuch and G. Wendt, 2. physiol. Chem., 1967, 348, 471. 180

6

CH,R R1COOj

CHzR CoASCOR2

CH,00CR2

RlCOO] CHzOH

1,2-diacyl-syn-glycerol 3-phosphoric acid lS7 where the N-acyl group is derived from a fatty acid. 3-0-Alkyldihydroxyacetonephosphate (80; R = OAlkyl) is an intermediate in the biosynthesis of 0-alkyl lipids.lS8 Enzymic reduction of (80; R = OAlkyl) with NADPH and acylation of the alcohol produced gives an 0-acyl 0-alkyl phospholipid (81). Hydrolysis of (81) by a phosphatase followed by further acylation produces 0-alkyl di-0-acyl lipids,

7 Enzymology Monomethyl phosphate hydrolyses at a faster rate in the presence of triethylenetetraminecobalt(1n)ion (82) than in the presence of pentamminecobalt(II1)ion,lsa and at a faster rate than dimethyl phosphate in the presence m7 R. Aneja, J. S. Chadha, and

401. lS8

la9

J. A. Knaggs, Biochem. Biophys. Res. Comm., 1969, 36,

F. Snyder, B. Malone, and M. L. Blank, J. Biol. Chem., 1970, 245, 1800. F. J. Farrell, W. A. Kjellstrom, and T. G. Spiro, Science, 1969, 164, 320.

Phosphates and Phosphonates of Biochemical Interest

151

of (82). It has been suggested that the bidentate nature of (82) is an important factor in this reaction and that the formation of the complex (83) facilitates the hydrolysis. It is possible that metal ions are near the active sites of phosphorylating enzymes and formation of similar complexes would assist phosphoryl transfer.

0 It 0+MeOP’ + ‘0OH2

(82) CH,OCOPh

I -

co I

CH,OH (a) HC(0Me)

s (b)OH-

CH2R

ICH2COCH2OP(O)(OH)2 + RSH

I

-

I CH2R

------+

(a) POCI, (b)H,O

RSSR + I-

I ’ co I

CHZR

+ CH,COCH,OP(O)(OH)2

3-Halohydroxyacetone phosphates (80; R = Hal) have been prepared in aqueous solution but have not been is01ated.l~~They are specific activesite reagents for aldolase, triose phosphate isomerase,lgl and glyceraldehyde 3-phosphate dehydrogenase. (80; R = Hal) closely resembles the natural substrate e.g. (80; R = OH) for these enzymes lg2and is consequently bound to its active sites. Further reaction of the inhibitor occurs when it is bound to the enzyme and the products of this reaction can give evidence as to the nature of the active site. (80; R = Br or Cl) reacts with glutathione with the formation of the S-alkyl derivatives while (80; R = I) oxidises cysteine and glutathione to the corresponding disulphides. This difference in the mode of action of (80; R = Hal) depending on the relative electronegativities of the halogens is reflected in the reaction of these compounds with ald01ase.l~~ (80; R = Br or C1) has no effect but (80; R = I) rapidly inactivates the enzyme. Two moles of (80) are covalently incorporated per mole of enzyme and the majority of its 29 SH groups are masked. Some activity can be restored by treating the inactive enzyme with a reducing agent. A similar modification of the active site of glyceraldehyde lQo lg1

lo2 lSa

F. C . Hartman, Biochemistry, 1970,9, 1776. A. F. W. Coulson, J. R. Knowles, and R. E. Offord, Chem. Comm., 1970, 7. I. A. Rose and E. L. O’Connell, J . Biol. Chem., 1969, 244, 126. F. C. Hartman, Biochemistry, 1970, 9, 1783.

Organophosphorus Chemistry

152

(84)

3-phosphate dehydrogenase with o-iodosobenzoic acid (84) has been observed with the formation of sulphenic acids.lD4 The extent of hydration of D-glyceraldehyde 3-phosphate ( 8 5 ) in aqueous solution has been determined by 1H n.m.r. spectroscopy. Since the free aldehyde is the substrate for glyceraldehyde 3-phosphate dehydrogenase, the rate of conversion of diol into aldehyde can be the rate-limiting factor in the oxidation of (85) by NAD+ over a wide concentration range of the enzyme.lB5 Aldolase and triose phosphate isomerase both liberate free (85), and it appears that the relatively slow interconversion of diol and aldehyde does not restrict the rate of glycolysis. CHO

The bimolecular alkaline hydrolysis of Sarin (isopropyl methylphosphonofluoridate) (86) proceeds with nucleophilic attack on p h o s p h o r ~ s . ~ ~ ~ In the presence of a-cyclodextrin, which is known to have a catalytic effect on hydrolysis and esterification reactions,lD7stereospecific formation of an inclusion complex precedes the hydrolysis of (86).lD8 ( - )-(R)-(86) forms the least stable inclusion complex and is consequently the most reactive stereoisomer towards hydrolysis. It is of interest that (-)-(R)-(86) is the more reactive isomer as a cholinesterase inhibitor.lDBThe configuration around the phosphorus atom of phosphorylated cholinesterases appears to have a considerable effect on the rate of ageing of the inhibited enzymes.2oo The role of an acidic group of the enzyme in the ageing of phosphorylated cholinesterases has already been demonstrated,201and it is believed 2oo that this acidic group may form a hydrogen-bond with a phosphoryl oxygen atom of the (Rp)-isomer and hence nucleophilic attack occurs on the carbon atom of the active site leading to C-0 bond cleavage. The formation of an intramolecular hydrogen-bond is not favoured for the (&)isomer on steric grounds. Spin-labelling has been used to study the con194

196 196

197

198 189

aoo 201

D. J. Parker and W. S. Allison, J. Biol. Chem., 1969, 244, 180. D. R. Trentham, C. H. McMurray, and C. I. Pogson, Biochem. J . , 1969, 114, 19. L. Larsson, Acta Chem. Scand., 1957, 11, 1131. F. Cramer and W. Dietsche, Chem. Ber., 1959, 92, 1739. C. Van Hooidonk and J. C. A. E. Breebaart-Hansen, Rec. Trau. chim., 1970, 89, 289. H. P. Benschop, G. R. Van den Berg, and H. L. Boter, Rec. Trav. chim., 1968, 87, 387. J. H. Keijer and G . Z . Wolring, Biochim. Biophys. Acta, 1969, 185, 469. H. 0. Michel, B. E. Hackley jun., L. Berkowitz, G . List, E. B. Hackley, W. Gillilan, and M. Pankau, Arch. Biochem. Biophys., 1967, 121, 29.

Phosphates and Phosphonates of Biochemical Interest

153

formation of macromolecules for some years 202 and phosphorofluoridates bearing nitroxide residues (87) have been used recently to study the active sites of cholinesterases, chymotrypsin, and other enzymes.2o3 A change in the e.s.r. spectrum of (87) occurs on binding to an enzyme, and from the shapes of the e.s.r. spectra it appears that the active site in cholinesterase is nearer the surface of the enzyme than that in chymotrypsin.

(87)

Arg-Glu-Ile- Ser-Ile- Arg

I

OPO,H, (88)

It may not be universally known that trialkyl phosphates can have anticholinesterase activity 204 and show mutagenic Rabbit liver glycogen phosphorylase has been isolated both in the inactive (dephosphorylated) and active (phosphorylated) forms.2o6 Phosphorylation of the inactive form with 32P-labelledATP and rabbit muscle phosphoryl kinase resulted in the formation of the 32P-labelledactive enzyme which was degraded to a phosphorylated hexapeptide (88). The aminoacid sequence of (88)was similar to that of phosphorylatedhexapeptideswhich have been obtained from human 207 and rabbit muscle phosphorylase.20s

8 Other Compounds of Biochemical Interest Radioactive diphenyl phosphinothioic acid derivatives (89) have been used to introduce a 32P-labelinto immunoglobulins selectively and irreversibly under mild conditions.20Q(89; X = Hal or NCS) reacted with aminogroups of model compounds and formed covalently bound derivatives with y-globulin. (89; X = OH) also formed derivatives with the protein when used in conjunction with a condensing agent such as DCC, but in general the amount of incorporation of radioisotope was less than that observed with (89; X = Hal or NCS). 202

20s

204 206

a 06 a07 2 98

200

0. H. Griffith and A. S. Waggoner, Accounts Chem. Res., 1969, 2, 17. J. C.Hsia, D. J. Kosman, and L. H. Piette, Biochem. Biophys. Res. Comm., 1969, 36, 75. P. Bracha and R. D. O’Brien, Biochemistry, 1970, 9, 741. S. S. Epstein, W. Bass, E. Arnold, and Y. Bishop, Science, 1970, 168, 584. D. P. Wolf, E. H. Fischer, and E. G. Krebs, Biochemistry, 1970, 9, 1923. R. G. Hughes, A. A. Yunis, E. G. Krebs, and E. H. Fischer, J. Biol. Chem., 1962, 237, 40. E. H. Fischer, D. G. Graves, E. R. Synder Crittenden, and E. G. Krebs, J. Biol. Chem., 1959, 234, 1698. R. A. Spence, J. M. Swan, and S. H. B. Wright, Austral. J. Chem., 1969, 22,2359.

154

Organophosphorus Chemistry

-NH-CH-COI CHO

+ Pi

(90)

From a comparison of the 31P n.m.r. spectra of phosvitin and bovine a,-casein B with the spectra of model compounds, it has been concluded that the phosphoryl groups are attached to serine in both macromolecules.210 In the aerobic dephosphorylation of phosvitin in the presence of ferrous sulphate,211 all the phosphoserine residues are oxidised in a random manner 212 and ap-dehydrogenation occurs to produce orthophosphate together with aminomalonic semialdehyde residues (90). There is no incorporation of isotopic label from the solvent into (90) and hence the formation of an enol phosphate followed by hydrolysis during the oxidation reaction is unlikely. An intermediate in the biosynthesis of squalene, which occurs between farnesyl pyrophosphate and squalene itself, is the cyclic pyrophosphoryl ester of squalene-l0,ll-glycol (91),213 and not the pyrophosphate ester of a cyclopropane derivative of squalene as has been previously Milligram quantities of (91) have been isolated and its structure demonstrated by an elegant combination of n.m.r., mass spectrometry, and isotope incorporation Although the amount of (91) available was insufficient for the determination of its absolute stereochemistry, it has been predicted that it has the (lOS,119-configuration. Ketocyclophosphamide (92) has been used for many years in the treatment of certain forms of cancer. A metabolite in which the heterocyclic tetrahydro-2H-l,3,2-oxazaphosphorinring is unopened has been isolated recently from the urine of dogs after they have been treated with laclabelled (92).21s Spectroscopic investigation of the metabolite which decomposed in dilute aqueous acid suggested that it was the 4-ketoderivative (93) and this was confirmed by synthesis. 210

211 212 21J

214

215 216

C. Ho, J. A. Magnuson, J. B. Wilson, N. S. Magnuson, and R. J. Kurland, Biochemistry, 1969, 8, 2074. C. T. Grant and G . Taborsky, Biochemistry, 1966, 5 , 544. R. W. Rosenstein and G . Taborsky, Biochemistry, 1970, 9, 649. G. Popjak, J. Edmond, K. Clifford, and V. Williams, J. Biol. Chem., 1969, 244, 1897. H. C. Rilling, J. Biol. Chem., 1966, 241, 3233. E. J. Corey and P. R. Ortiz de Montellano, Tetrahedron Letters, 1968, 5 1 13. D. L. Hill, M. C. Kirk, and R. F. Struck, J . Amer. Chem. SOC.,1970, 92, 3207.

155

Phosphates and Phosphonates of Biochemical Interest

Cinnamyl pyrophosphate (94) reacts with resorcinol on heating in aqueous solution at neutral pH to give (95) and (96).217 Since (94) is not hydrolysed under the conditions of the reaction this model synthesis is confirmatory evidence that (94) could be a precursor in the biosynthesis of neoflavanoids.218 Me I RCH,C -CHCH2CH2CH=C / O\

I

\

-CH2R

Me

/O

o~p~OP*,H, (91)

where R = geranyl

(93)

(92)

w

CH20P206H3 Ph

(94)

(95)

+

(96) 217

218

J. Larkin, D. C. Nonhebel, and H. C. S. Wood, Chem. Comm., 1970,455. S. Mageswaran, W. D. Ollis, R. J. Roberts, and I. 0. Sutherland, Tetrahedron Letters, 1969, 2897; 0 . R. Gottlieb and W. D. Ollis, Chem. Comm., 1968, 1396; W. D. Ollis, Experientia, 1966, 22, 777.

8 Ylides and Related Compounds BY S. TRIPPETT

1 Methylenephosphoranes A. Preparation.-The generation of ylides by electrolysis has been modified by the inclusion of azobenzene, by the use of a potential at which only the azobenzene is able to accept electrons, and by the use of conditions under which the phosphonium salt is the only proton source. Thus electrolysis of a solution of azobenzene, benzaldehyde, benzyltriphenylphosphonium bromide, and lithium chloride in dimethylformamide at a potential of 0.9 V gave cis (59%) and trans (39%) stilbenes. The formation of ylides by the addition of nucleophiles to vinylphosphonium salts has been applied to a-acylvinyl salts., Addition of the malonate anion to the salt (1) gave the ylide (2).

Ph3$.C(C0.Pri):CH2 el

-

+ CH(CO,Et),

(1)

Ph3P:C(CO.Pr').CH,-CH(CO,Et), (2)

The trimethylsilyl group has been used to protect the ethynyl group of the salt (3) during ylide f ~ r m a t i o n .The ~ Wittig reaction with the aldehyde (4) succeeded only when the salt (3), the aldehyde, and sodium hydride were stirred together in tetrahydrofuran-dimethyl sulphoxide (3 : 2) under nitrogen at 0 "C. The protecting group was subsequently cleaved by treatment with silver nitrate. Me,Si.CIC.CH,.CH,.~Ph,i+ OHC.(CH,),.CO,Me (3)

(4)

------+

Me,Si.CiC.CH,.CH:CH.(CH,),.CO,Me 4 6 5 0 % of 95% cis

The formation of ylides by the addition of phosphines to activated acetylenes has been extended to the synthesis of the bisphosphoranes (5),4 (6),5 and (7),6 the last being formed from the initial adduct by a proton 1

a 8

4 6 6

P. A. Iverson and H. Lund, Tetrahedron Letters, 1969, 3523. E. Zbiral, M. Rasberger, and H. Hengstberger, Annalen, 1969, 725, 22. A. G. Fallis, E. R. H. Jones, and V. Thaller, Chem. Comm., 1969, 924. M. A. Shaw and J. C. Tebby, J . Chem. SOC.(C), 1970, 5 . A. N. Hughes and S. W. S. Jafry, J . Heterocyclic Chem., 1969, 6, 991. M. A. Shaw, J. C. Tebby, R. S. Ward, and D. H. Williams, J . Chem. SOC.( C ) , 1970,504.

157

Ylides and Related Compounds

shift. The 1,4-diphosphorins (8; R = OMe or Ph) formed from cis-1,2bis(dipheny1phosphino)ethylene were too unstable for complete characterisation.6

Ar-CO.CiC*CO.Ar + R,P --+

R3P,,c--c,

Ar.OC

,CO-Ar PR3

13Cand lsO Isotope effects in the decomposition of the salt (9) in acetic acid-acetic anhydride have been interpreted in terms of a rate-determining step involving formation of the methylenephosphorane.7

+

-

Ph3P-CH2*CO2CHPh2 (9)

R.D.S.

Ph3P:CH,

+ + C 0 2 + CHPh,

For the formation of diphenylmethylenetriphenylphosphorane on photolysis of triphenylphosphine and benzophenone in benzene solution * see Chapter 10, Section 1. Ylides have been implicated as intermediates in several reactions, among them the deoxygenative dimerisation of carboxylic anhydrides by triethyl ph0sphite.O Here the ylide (10) was trapped with benzaldehyde to give the benzylidenethiaphthalide (11). The product originally obtained lo from triphenylvinylphosphonium bromide and the sodium salt of benzoin

lo

S. Seltzer, A. Tsolis, and D. B. Denney, J. Amer. Chem. SOC.,1969, 91, 4236. L. D. Westcott jun., H. Sellers, and P. Poh, Chem. Comm., 1970, 586. C . W. Bird and D. Y. Wong, Chem. Comm., 1969,932. E. E. Schweizer and J. 0.Liehr, J. Org. Chem., 1968, 33, 583.

-

Ph .CO CH(0). Ph

11 -

-

Ph3$ CH2 CH, .CPh(6) CO Ph

has now been shown l1 to be the quinquecovalent phosphorane (13) formed via the ylide (12). Methylenetriphenylphosphorane is presumably an intermediate in the formation of the olefin (14) from triphenylphosphine and cyclopropyl phenyl ketone,12and the keten-ylide (15) is involved in the formation of the irninocyclobutenone (16) from diphenylcyclopropenone and 2,6-dimethylphenyl isocyanide catalysed by triphenylphosphine.l3 A solution of the ylide (1 5 ) was formed when triphenylphosphine and diphenylcyclopropenone were stirred in benzene at room temperature. The solution gave (16) and triphenylphosphine when treated with the isocyanide, while with methanol methyl cis-2,3-diphenylacrylate and triphenylphosphine were formed in high yield. l1 l2 lS

E. E. Schweizer, W. S. Creasy, J. G. Liehr, M. E. Jenkins, and D. L. Dalrymple, J . Org. Chem., 1970, 35, 601. E. E. Schweizer and C. M. Kopay, Chem. Comm., 1970, 677. N. Obata and T. Takizana, Tetrahedron Letters, 1970, 2231.

-

159

Ylides and Related Compounds PCO-Ph

+ Ph,P

200 ‘C.

+ Ph,P.CH,CH,*CH*CO*Ph

J

P

h

0

a

\ Ph3P:CH,

+ CH,:CH*CO.Ph

+ Ph,P (14) 11%

p h b O Ph’

Ph,P

+

+ Ph3P

Ph, C ,CO,Me

/I Ph/CLH

c -

w Ph,P.CPh.CPh:C:O

+?

Ph P -C Ph -C P h

I It

2 1 1

C-LC PhN

II

0

phqo +

Ph

Ph3P

NPh (16)

B. Reactions.-(i) Inorganic Reagents. The ester phosphoranes (1 7 ; R = Me or Et) with tetrafluorohydrazine in dibutyl sebacate at room temperature gave nitrogen, difluorotriphenylphosphorane, and the corresponding difluoroacetates in 50-60% yield.14 Ph,P: CH.CO,R (1 7)

+ NZF,

Nz +Ph,PFZ

+ CHFZ. CO,R

Further reactions of nitrosyl chloride with ylides to give initially a-oximinoalkylphosphonium chlorides have been described.16 Ylides react with periodate anion to give carbonyl compounds, phosphine oxide, and iodate anion probably via the intermediates (18).l6 When the stable ylides (19) were boiled with aqueous periodate the resulting l4 l6 l6

A. V. Fokin, Yu. N. Studnev, L. D. Kuznetsova, and A. F. Kolomeets, Zhur. obshchei Khim., 1969,39, 2367. C. Eguchi, K. Akiba, and N. Inamoto, Bull. Chem. SOC. Japan, 1970, 43, 438. H. J. Bestmann, R. Armsen, and H. Wagner, Chem. Ber., 1969, 102, 2259.

Organophosphorus Chemistry

160

102-+104-

-

210,-

a-diketones were isolated in 28-100% yield. The ylides may be generated in situ by the action of base on the phosphonium periodate. If the initial product is an aldehyde it reacts with a further molecule of phosphorane Ph,P: CRI. CO * R2 (19) 2Ph3$.CH2RI04R Olefin %

I I

2NaIO4

Ph,PO

+ R1.C0.CO*R2+ 2NaIO3

R.CH:CH.R

+ Ph,PO + 210,-

AC PhCO C02Et Ph PhCH:CH2 PhCH2*CH2 C3H, 79 70 83 81 52 33 13

to give olefin. The intramolecular version of this reaction has been applied to the synthesis of several polycyclic systems, among them (20) and (21).

(ii) Halides. A general 1,5-diene synthesis has been developed l7 based on the reaction of allylic bromides with allylidenephosphoranes and reduction of the resulting salts. It is illustrated by the synthesis of alltrans-squalene (23) in 65% yield based on the salt (22). Using allylic bromides, no coupling occurred at the y-position of the allylidenephosphoranes ; with chlorides, some 5-1 5% of y-coupling was observed. The reaction of ylides with a-bromo- or, preferably, a-iodo-esters to l7

E. H. Axelrod, G. M. Milne, and E. E. van Tamelen, J. Amer. Chem. Soc., 1970, 92, 2139.

Ylides and Related Compounds

R1R2C :CH . C H 2 0 H

161

CBI

K I R K :C1-I.C'11,Br

--&D

Ph3P

R1R2C:CH.CH:PBu,

I

PhLi R1R2C:C H - C H , - ~ B U ,BrTHF - 7 6 "C (22)

t---

R'RT: CH .CH2Rr

R'R2C:CH-CH.6Bu,,

I

Br-

Li

(R1R2C:CH.CHJ2 (23)

R1R2C:CH.CH,

give a$-unsaturated esters l8 has been greatly extended.ls When R1, R3 = H and R4 = Me, the larger the group R2 the smaller the proportion

-

Ph,P :CR1R2 + R3- CHX .C0,R4

-

-

Ph3$- CR1R2 CHR3 C02R4 X-

I+

Ph3P: CR1R2

R1R2C:CR3-C02R4+ Ph,P 51-82%

+ Ph3P.CHR1R2 X-

of cis-isomer in the resulting ester. Methyl y-bromocrotonate and benzylidenetriphenylphosphorane gave the dienic ester (24) in 85% yield. The intermediate salt in the reaction of the same ylide with methyl bromodideuterioacetate was shown to undergo 47% of a-elimination and 53% of p-elimination from the deuterium distribution in the resulting methyl cinnamate. 2Ph3P:CHPh

l8

l9

+ BrCH,

.

* CH :CH C02Me > PhCH: CH. CH: CH. C02Me (24)

+ + Ph3P + Ph,P. CH,Ph

Br-

H. J. Bestmann, K. Rostock, and H. Dornauer, Angew. Chem. Znternat. Edn., 1966,5, 308. H. J. Bestmann, H. Dornauer, and K. Rostock, Chem. Ber., 1970, 103, 685.

162

Organophosphorus Chemistry

+

Ph,P:CHPh

BrCD,-C0,Me --+ Ph,6*CHPh.CD,.CO2Me Br-

ACHPh Ph-CD :CD .CO,Me

[Ph,P :CPh -CD,.CO,Me]

+---

Ph. CH: CD .CO,Me

47%

The phosphonium salts resulting from the reactions of the stable ylides (25) with iodosobenzene dichloride eliminate hydrogen chloride on refluxing in benzene, to give the a-acylvinyl salts (26)., If wet benzene is used, these then undergo a reverse aldol reaction, e.g. (27) gives (28).

-

Ph3P:C(CH2R1) CO * R2 (25)

PhICl2

c

> Ph3P.CCI(CH2R1)*CO*R2C1-

+1

Reflux

C6H6

Ph3P*C(C0. R2):CHRl Cl(26)

-

Ph$* C(C0 Pr') :CHEt (27)

61

H20

-

> Ph3$. CH, * CO Pri El + [Et CHO] (28)

.

Methylenetriphenylphosphorane with phosphorus trichloride, phosphoryl and thiophosphoryl chlorides gave the stabilised ylides (29), (30),

POCl

6Ph3P:CH,

\

(Ph,P :CH),PO + 3Ph3kH3

C1'

(30)

PSCI,

(Ph,P :CH),PS + 3Ph,hCH3

C1-

(31) (Ph,P :CH * CH :CH),PPh PhPCI,

Ph,P: CH-CH:CH2 /

+

Ph,P :CH * CH :CH *PR2

(R.=R,PCl Et or Ph)

[

]

(Ph,P:CH-CH:CH),P

Ylides and Related Compounds

163

and (3 1) respectively.20 Allylidenetriphenylphosphorane (32) coupled with phosphorus trichloride and with chlorophosphines at the y-position, transylidation then leading to stabilised ylides.20 Exchange of chlorosilyl for trimethylsilyl groups occurs when the bis(trimethylsily1) ylide (33) is treated with the chlorosilanes MenSiC1+n) ( n = 0, 1, or 2) and with related compounds.21 The bis(chlorodimethy1silyl) ylide (34) with metallated methylenetrimethylphosphorane gave the Me3P:C(SiMe,Cl),

Me,P: C(SiMeCl&

/

(3j)

Me,P :C(SiMe,),

ClCH,SiMeCl,

Me,SiI

Me,P: C(SiCl,),

\ SiC13

Me3P:C(SiMeC1-CH,Cl),

/

Me3+- C(SiMe,), .I-

Me3P:C

\

Si Me,

four-membered bis-ylide (35) previously obtained 22 from methylenetrimethylphosphorane and dichlorodimethylsilane. The latter reaction probably involves the intermediate bis-ylide (36), which can be isolated if the methylenephosphorane is always present in excess and which has also been prepared as shown.

Me,P :CH,

+

Me,SiCl,

4: 1 L__+

61%

Me,P :CH -SiMe, CH :PMe, (36)

T

BuLi 26%

Me,P 2o

21 22

-i- (ClCH,),SiMe,

DMF

(Me,$-CH,),SiMe,

2C1-

K. Isslieb and M. Lischewski, J . prakt. Chem., 1969, 311, 857. H. Schmidbauer and W. Malisch, Angew. Chem. Internat. Edn., 1970, 9, 77. H. Schmidbauer and W. Malisch, Chem. Ber., 1970, 103, 97.

Organophosphorus Chemistry

164

( 5 ) Cnrbonyls. The preferred formation of cis-olefin in Wittig olefin syntheses carried out in non-polar solvents in the absence of salts has been explained 23 in terms of initial co-ordination of the aldehyde oxygen with phosphorus, the oxygen occupying the apical position of the trigonalbipyramidal complex (37) shown in its least sterically crowded form. Formation of a bond between C+ and C- is held to be more readily accomplished by anticlockwise rotation about the C+-0 bond, to give the precursor (38) of the cis-olefin, than by clockwise rotation, which would +,K’ 0-c,

I

0

H Ph-

I

1 R2

Ph

Ph R2

(37)

(38)

lead to trans-olefin, since the latter would require greater rotation and serious interaction between R1and an equatorial Ph group. It is important to remember that the oxaphosphetan ring is not planar. P-Oxido ylides (39), readily prepared 24 by deprotonation of the betaines resulting from the addition of Wittig reagents to aldehydes, promise to be of very great synthetic utility. Their protonation 26 is a stereospecific process leading to threo-betabe and hence to trans-olefin. They are Ph,P:CHRl

+

R2CH0

-

1-R’CH: CHR’

.f

249

Ph,P.CHR1*CHR2(0)

I

R1.i - 78°C

Ph,P: CR1.CHR2(0) (39)

threo-Ph3Pf .CHR’ * CHR2(6)

f

2y

24 25

W. P. Schneider, Chem. Comm., 1969, 785. M. Schlosser and K. F. Christmann, Annalen, 1967, 708, 1. E. J. Corey, J. I. Shulman, and H. Yamamoto, J . Amer. Chem. SOC.,1970, 92, 226.

Ylides and Related Compounds

165

inethylated by methyl iodide in a non-stereospecific process 26 but do not react with most alkyl halides.25 Treatment with N-chlorosuccinimide followed by elimination of phosphine oxide gives chl~ro-cis-olefins,~~ while use of iodosobenzene dichloride gives the chloro-trans-olefins.26$ 27 With bromine, the p-oxido-ylide (40; R = Ph) gave p-methyl-cis-wbromostyrene in low yield,26but with (40; R = C6H13)neither bromine nor iodine led to halogeno-~lefin.~~ However, this iodination reaction gave methyl heptyl ketone (52%), perhaps via the a$-epoxyphosphonium salt (41). This gives a general route for the conversion: R1*CHO+R1*CH,.CO*R2. 25s

Iodo-olefins can be obtained from IS-oxido-ylidesby addition of mercuric acetate at - 100 "C followed by elimination of phosphine oxide at 25 "C and treatment of the product with anhydrous lithium iodide and iodine. c-Ph*CBr:CHMe 2 3 '7"

I

Br, R = Ph

Ph,P:CMe.CHR(O-) (40)

Me P h3P* C -CH-CGH,3 \ /

0

(41) I

! H,O

JI

Me.CO.C,H Thus from (40; R = C&13), 40% of 2-iodo-trans-2-nonene (42) was obtained.26 Fluoro-olefins have also been obtained from p-oxido-ylides by reaction with perchloryl fluoride.26 Perhaps the most important reaction of p-oxido-ylides so far investigated is that with aldehydes 25 which, after elimination of phosphine oxide, leads to a,/%unsaturated alcohols having a tri-substituted double bond [e.g. (43)]. In general, that oxygen is eliminated which originates in the second aldehyde used in the synthetic sequence. Thus ethylidenetriphenylphosphorane treated successively with benzaldehyde, butyl-lithium, and 1-deuteriobenzaldehyde gave the alcohol [(44); 74x1 with deuterium exclusively at C-3, while use of acetaldehyde and heptanal in that order in the same synthetic sequence gave the alcohol [(45); 67x1. The observed 28 27

M. Schlosser and K. F. Christmann, Synthesis, 1969, 1 , 38. E. J. Corey, J. I. Shulman, and H. Yamamoto, Tetrahedron Letters, 1970, 447.

166

Organophosphorus Chemistry

stereochemistry in these reactions shows that the intermediate /3,/3’dioxido-phosphonium ions must have the geometry (46), and not that of the corresponding erythro-form, in order for the groups R1and RZto be in different environments with respect to the phosphorus. Ph$Et

% Ph3P:CH.CH:,

-

R’*CHO -78 “C

Ph,h.CHMe.CHR1(6) -78 “C

c

Me.

?H I R’CH, /H Me/C’KR2

+

PPh -.H ‘CZR2

R1. X’ H

)c’

I 0-

I

0-

(43)

The same sequence of reactions starting from ethylidenetriphenylphosphorane and using the aldehyde (47) and paraformaldehyde in that order gave santalol (48),25the direction of the elimination presumably being dictated by the thermodynamic stability of the resulting olefin.

Partial asymmetric synthesis has been observed in the reactions of the (R)-ylide (50), obtained from the )-salt (49), with 4-substituted cyclohexanones to give the (S)-olefins (51).28 The olefin (51; R = Me) was obtained in an optical yield of 43%. Optically active olefins of unknown absolute configuration or optical purity were obtained from the ylide (50) and tropinone, pseudopelletierine, and the ketone (52).

(a-( +

as

H. J. Bestmann and J. Lienert, Angew. Chem. Internat. Edn., 1969, 8, 763.

+ (50)

--+

Various halogen-substituted butadienes (53) have been prepared from acraldehydes by reaction with dibromomethylenetriphenylphosphorane generated in situ.2s The corresponding dichloro-ylide did not react. Ethyl CX,: CX. CHO

+ CBr, + Ph,P

"t:

>

CX, :CX * CH :CBr, (53) e.g.

CCl, :CH CH :CBr, 76%

pyruvate with these ylides gave the unsaturated esters (54) and ( 5 9 , while the keto-acetal (56) with an excess of the dichloro-ylide gave the unsaturated acetal (57). CI,C :CMe * C0,Et Ph3P-CCld

(54)

39%

-

Br,C :CMe C0,Et

(55)

66%

%Ph.C(:CCl,).CH(OEt),

Ph P-CCI

PhSCO *CH(OEt), (56)

(57)

71.5%

The chlorine-substituted pentadienal (58) has been reacted with various stable ylides as The a-keto-aldehyde (59) reacted, as expected, with stable ylides at the C. Raulet and E. Levas, Compt. rend., 1970, 270, C, 1467. m o A. Roedig, G. Markl, and H. Schaller, Chem. Ber., 1970, 103, 1011.

168

Organophosphorus Chemistry CI, c ,1 ,C=C, ,c=c ,CHO c1 \Cl Cl

Ph,P : CH.CO,Me

ReCHICH-CO,Me

N

50 "C

73%

\

(58)

I

R CH E C B ~ . C O , M ~

Ph,P : CH-CHO 50 "C

88%

R .CH f CH .CHO 89%

\m ~

Ph:,P : CR'-C02R?

Ph-CO-CHO

(59)

-

Ph CO - CH :CR' * C02R2 = H, CH,Ph or CH,.CO,hle

R

\ /

C H * CO * Ph

t

PPh,

95.8%

(60) 91% m.p.175-180

"C(decomp.)

aldehyde group to give a,/hnsaturated 32 With cyclopentadienylidenetriphenylphosphorane, a compound was obtained to which the structure (60) was The acid-catalysed Wittig reactions of the stable phosphoranes Ph3P:CH-R (R = COzEt or CN) with 3-0x0-steroids having no a-substituents, proceed with the same stereochemistry as the corresponding reactions under basic condition^.^^ Steroids with keto-groups at the 2-, 4-, 6-, 7-, 11-, 12-, and 16-positions failed to react with these ylides in refluxing benzene in the presence of benzoic acid. Ylides have been used to prepare the various cyclopropyl-substituted ethylenes, except tetracy~lopropylethylene.~~ The ylide (61) gave the expected olefin with benzaldehyde but did not react with dicyclopropyl ketone. 31

sa 8a a4

M. I. Shevchuk, A. F. Tolochko, and A. V. Dombrovskii, Zhur. obshchei Khim., 1970, 40, 57. M. I. Shevchuk and A. V. Dombrovskii, Zhur. Vsesoyuz. Khim. obshch. im. D. I . Mendeleeva, 1969, 14, 23 1. A. K. Bose, M. S. Manhas, and R. M. Ramer, J. Chem. SOC.(C), 1969,2728. S . Nishida, I. Moritani, E. Tsuda, and T. Teraji, Chern. Comm., 1969, 781.

Ylides and Related Compounds Ph,P:C(a),

+ PhCHO

-

169 PhCH:C

(4

(61)

Enol-lactones (62) have been obtained from stable ylides and cyclic five-rnernbered aliphatic anhydrides, both saturated and unsat~rated.,~ Mixtures of cis- and trans-isomers were sometimes obtained. The reaction

li

6 +y$ H\

+ Ph,P:CH-CO.R R

=

--+

C0.R

R.OC

0

0

Alkyl or alkoxyl

(62)

failed with maleic anhydride, but the desired enol-lactone was obtained using the adduct of rnaleic anhydride with furan followed by a retroDiels-Alder reaction. The adducts from ylides and isothiocyanates36 remain as the betaines (63) when R1has a + I effect but undergo proton transfer to give the stable ylides (64) when R1has a - I effect or is hydrogen. Both (63) and (64) are Ph,P:CHR1

+

-

Ph3P.CHR1*C(S):N*R2 (63)

R'NCS

R3* CHO,

R3CH:CR1.CS.NHR2 <

(63) or (64)

Me1

1

Ph,P :CR1.CS *NHR2 (64)

Ph,6.CR1:C(SMe)-NHRz I-

R3*CH0

R3CH:CR1-C(SMe):NR2+--- Ph3P:CR1.C(SMe):NR2 (65)

-

Ph,$ * CR1:C(SMe) *NMeR2 I-

RICH, C(SMe) :NR2

(67)

(66)

A. P. Gara, R. A. Massy-Westropp, and G. D. Reynolds, Tetrahedron Letters, 1969, 4171. 36

H. J. Bestmann and S. Pfohl, Angew. Chem. Internat. Edn., 1969, 8, 762.

170

Organophosphorus Chemistry

methylated on sulphur with methyl iodide. The resulting salts can be converted into the ylides (65), which can be hydrolysed to the thioimidic acid derivatives (66) and which with methyl iodide are N-methylated to give the vinylphosphonium salts (67). Various 2-fury1 isocyanates and isothiocyanates as well as 2-furoyl isothiocyanate have been treated with stable ylides to give carbamoyl- or thiocarbamoyl-methylenephosphoranes.37 From i.r. and n.m.r. evidence these have strong intramolecular hydrogen bonds, e.g. (68). QEt

(68)

(iv) Miscellaneous. Carbophosphoranes have been reviewed.58 At 100 "C in benzene the ylide (69) underwent a [3,2]-sigmatropic rearrangement to give the phosphine (70) in 7% yield.39 The major products (71), (72), and (73) were formed by the competing dissociation-

recombination mechanism. No product corresponding to a Stevens

(74)

rearrangement of the ylide was isolated. The reverse of the above [3,2]sigmatropic rearrangement did not occur when the phosphine (74) was heated with benzaldehyde at 200 "C. 37

as 38

H. Saikachi and K. Takai, Yakugaku Zasshi, 1969, 89, 1401. C. N. Matthews and G. H. Birum, Accounts Chem. Res., 1969, 2, 373. J. E. Baldwin and M. C. H. Armstrong, Chem. Comm., 1970, 631.

Ylides and Related Compounds 171 A further report has appeared40 of the reactions of stable ylides with nitrileimines to give pyrazoles. The reactions were carried out in one step in refluxing chloroform in the presence of triethylamine. The aroyl- and sulphonyl-aziridines (75; R1= Ph-CO or p-Me*C6H4-SO2) with the ester phosphorane (76) gave the stable ylides (77) in high yield, while the aziridine (75; R1= p-NO,*C,H,.CO, R2= H) with the ester phosphorane (78) gave the 2-pyrroline (79).4f The Schiff base (81) was obtained from the trans-aziridine (80); the Wittig reaction is unlikely to have followed isomerisation of the aziridine to the ketone, which would be unreactive under the reaction conditions.

R2 RI."$

(75)

+ ph3P:CH.C02Et

\

(76)

a R1.NH*CHR2*CH,*C(C02Et):PPh3 Toluene

R2= Hor Me

(77)

(78j

+ Ph,PO (79)

A full account has appeared of the reactions of the ylides (76) and (78) with acyl a z i d e ~ .Triazoles ~~ are also formed in the reactions of the stable ylides (82) with acetyl azide or on acylation followed by treatment with amounts of the azido-olefins (83) and (84) are sodium a ~ i d e . ~Variable , also formed, e.g. (82; R1= Me, R2= OEt) gives 80% of (83) as a mixture of isomers. The reversible nature of the steps (82) + (85) + (86) is shown by the action of sodium azide and isobutyryl azide on the salt (87) to give a mixture of N-acetyl- (6&70%) and N-isobutyryl-triazoles. From data on the lH n.m.r., i.r., and U.V. spectra and on dipole moment measurements of the fluorenylidenephosphoranes (88) it has been concluded that the mesomeric effect of the substituent X in the group p-X.CBH4attached to phosphorus in these ylides has an influence throughout the whole molecule, but that this is small compared with mesomeric effects in planar p,, conjugated R. Fusco and C. P. Dalla, Chimica e Industria, 1970, 52, 45. H. W. Heine, G . B. Lowrie 111, and K. C. Irving, J . Org. Chern., 1970, 35, 444. G . L'Abbe, P. Ykman, and G. Smets, Tetrahedron, 1969, 25, 5421. 43 E. Zbiral and J. Stroh, Monatsh., 1969, 100, 1438. o4 H. Goetz and B. Klabuhn, Annalen, 1969,724, 1. Q0 41

Organophosphorus Chemistry

172

R ( R2CO) C :C Me - N, (83)

+

Ph,P:CR1*C0.R2

+I' Ph3P-C R'-CO*R2

CH3*C0.N3

(82)

R1= Alkyl or OEt

G-A-Me

I

R2= Alkyl, Aryl, erc.

N3

(85)

0

+

I1

7 -C-

Ph3P-R'

R2

+

Ph,P -CR1-C0.112 I CO-Me

N3-

6

Ph36

I

I

R'C-CR2 /

N\

\

N

,N-CO-Me

R'

R2

m

NqN"-

co.Me

R1(MeCO)C:CR2.N3 (84) 3H Nq ,N-CO-CHMe,

N 4 ;Me,CH.CO.N, 1

+

C0,Et

I

Ph,P-C-COeMe I C3H7

C02Et N3 N3+ I I 2 Ph,P-CC-Me I I C3H7 0-

Ph,P:C(C3H,)-C02Et

+ CH,.CO*N, I

(87)

C,H7

OEt

/-\N-CO*Me

173

Ylides and Related Compounds

PR, (88)

R

=

ArPr,, ArPh, or Ar,

For the mass spectra of stable phosphoranes see Chapter 11, Section 9, and for the photolysis of phosphoranes see Chapter 10, Section 1. For the n.m.r. spectrum of the ylide Ph,P:CH*CHO see Chapter 11, Section 1. 2 Phosphoranes of Special Interest While the triphenylphosphonium salt (89; R = Ph) works well in olefin synthesis using sodium methoxide as base in dimethylf~rmamide,~~ the tributylphosphonium salt (89; R = Bu) or the keto-phosphonium salt (90) with potassium t-butoxide gives largely a mixture of the oxaphosphans (91) and (92), containing 7-12% of the latter.46 R36'(CH,),-c?)

M/e

*

1-

is91

RKOBut = Hu

+

'

DMF

R,P*(CH,),.CO.Me

Em".

H2C

I-

+

(91)

75%

0 B u 3 (92)

(90)

The cumulative ylide (95) has been obtained by treating either of the salts (93) and (94) with triethylamine in a~etonitrile.~'With reactive Ph:,;.CH,-CBr: CPh, Br-

Ph,P: C: C :CPh, (95)

1 x Et,N

Ph,$ CH :C :CPh, Br-

Ph36.CH,*C(NHPh):CPh, Br-

(96)

- I

PhLi

-

ArCH :CH C(NHPh) :CPh, 45

46

47

Ar-CHO

Ph,P: CH C(: NPh) -CHPh,

(98) (97) E. A. Oboz'nikova, M. Ts. Yanotovskii, and V. I. Samokhvalov, Zhur. obshchei Khim., 1964,34, 1499. L. P. Davydova, L. N. Kaboshina, E. A. Oboz'nikova, I. M. Kustanovich, and G. I. Samokhvalov, Zhur. obshchei Khim., 1968, 38, 2091. K. W. Ratts and R. D. Partos, J. Amer. Chem. SOC.,1969, 91, 6112.

174

Organophosphorus Chemistry

-

H2O

[MeN :C: C: C :CPh,] > MeNH CO * CH :C: CPhz (100) 28%

Ml o:

ArCHO

(95)

ArCH:C:C:CPh, (101) 60-70%

Ph&: C: 0

[PhZC:C :C :C :CPh,], (102)

aromatic aldehydes it gave the butatrienes (101) and with methyl isocyanate followed by water gave the amide (loo), perhaps uia the imine (99). A dimer of the pentatetraene (102) was obtained from the ylide (95) and diphenylketen. The allenic salt (94) did not add methanol or t-butyl sulphide, but with aniline the salt (96) was obtained. This with phenyllithium gave the imino-stabilised ylide (97) from which the amino-diene (98) was obtained on treatment with 3,4-dichlorobenzaldehyde. Ph,$ -CH:C(OEt),

BF,-

NaNH 4 Ph,P :C :C(OEt), NH,

(103)

/'

RICH,. CO * R2

RZ= Ph, Me, OEt

J

Ph3P:CH.C(OEt):CR1.CO-R2

Fluorenone

a J.

/

\

(106)

I

PhCHO

PhCH :CH *C(OEt):CR' .CO. R2 (1 07)

tr,o

-I I i.

OEt

Ph

OEt (105)

65%

Ylides and Related Compounds

175

With fluorenone the 2,2-diethoxyvinylidene-ylide(103) gave the expected allene (104), isolated as the dimer (105), but the reaction with carbonyl compounds containing an a-methylene group was quite different.48 Michael addition followed by the elimination of ethanol gave the stable ylides (106). These in olefin synthesis with benzaldehyde gave the ketones (107), hydrolysis of which led to the /3-diketones (108). In the n.m.r. spectrum of the ylides (106; R1= H), the y-proton was split into a doublet by the phosphorus ( 4 J p= ~ 6.5 Hz). 3 Selected Applications of the Wittig Olefin Synthesis A. Natural Products.-(i) Prostaglandins. In syntheses of prostaglandins E2 and F2ar (both dl 4 9 ~6o and optically active "') the cis-olefinic side-chain was introduced using the ylide (1 10) generated in dimethyl sulphoxide. Thus the lactol (109) gave the acid (111) in > 80% yield. The ylide (110) under these conditions also gave cis-olefins with simple aldehydes.

PH + Ph,P:CH-(CH,),.C02-

&C5H,,

RO

OR

\DMSO

In the course of a synthesis of (+)-prostaglandin E3 methyl ester, the aldehyde (1 12) with the acetylenic ylide (1 13) gave the acetylene (1 14).62 The tributylphosphorane (1 16) was used in a synthesis of ( k )-prostaglandin El methoxime in order to introduce the required side-chain into the aldehyde (1 15).53 (ii) Isuprenuids. A general method for the elaboration of isoprenoid chains, one unit at a time, uses the ylide from the salt (117) followed by hydration 4s 49

50 51

62

53

H. J. Bestmann and R. W. Saalfrank, Angew. Chem. Internat. Edn., 1970, 9, 367. E. J. Corey, N. M. Weinshenker, T. K. Schaaf, and W. Huber, J. Amer. Chem. SOC., 1969,91, 5675. E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 31 1. E. J. Corey, T. K. Schaaf, W. Huber, U. Koelliker, and N. M. Weinshenker, J. Amer. Chem. SOC.,1970,92, 397. U. Axen, J. L. Thompson, and J. E. Pike, Chem. Comm., 1970, 602. N. Finch and J. J. Fitt, Tetrahedron Letters, 1969, 4639.

176

Organophosphorus Chemistry

H

A

w

CH :CH-CH,.CiC-Et

C02Et I

76%

>-

74% --+

21% all-fruns

39X all-tram

Ylides and Related Compounds

177

of the terminal acetylene in the product, a mixture of cis- and tvansisomers.54 The ylide (118) allows a similar addition of Clo-units, a process ~ ~ method has which can be repeated after hydrolysis of the a ~ e t a l .This been used in the synthesis of chlorobiumquinone. The high proportion (65%) of the cis-olefin formed in the reaction of the ylide from the salt (119) with the aldehyde (120) has been ascribed to stabilisation of the erythro-betaine by orbital overlap, as in (121).56

Methyl natural bixin (122) has been synthesised as The labelled (3H) ester phosphorane (123) has been used to prepare the thioethers shown for biosynthetic studies in Anthemis species.s8 The reaction of the ester phosphorane (125) with a-halogenocarbonyl compounds has been applied to the elaboration of steroid side-chains in isocardenolide synthesis, i.e. (124) -+ (126).60 A detailed study has been made of the reactions of 20-0x0-steroids with methoxymethylenetriphenylphosphorane.61 Isopropylidenetriphenylphosphoranehas been used in the synthesis of trans-2,6-farnesol and of trans-nerolidol and, labelled with 14C, in the preparation of 14C-labelled ( + )-trans-chrysanthemum mono- and dicarboxylic acids and related Methylenation with methylenetriphenylphosphorane has been used in b4 66 66

67 68

6a

6o

62

6s

K. Sato, S. Inoue, and S. Ota, J . Org. Chem., 1970, 35, 565. W. E. Bondinell, C. D. Snyder, and H. Rapoport, J . Amer. Chem. SOC.,1969,91,6889. J.-L. OlivB, M. Mousseron-Canet, and J. Dornand, Bull. SUC.chim. France, 1969,3247. G . Pattenden, J. E. Wray, and B. C. L. Weedon, J . Chem. SOC.( C ) , 1970, 235. F. Bohlmann and W. Skuballa, Chem. Ber., 1970, 103, 1886. H. J. Bestmann, K. Rostock, and H. Dornauer, Angew. Chem. Internat. Edn., 1966, 5 , 308. G. R. Pettit, B. Green, A. K. Das Gupta, P. A. Whitehouse, and J. P. Yardley, J . Org. Chem., 1970, 35, 1381. G. R. Pettit, G. L. Dunn, and P. Sunder-Plassman, J. Org. Chem., 1970, 35, 1385. 0. P. Vig, J. C. Kapur, and C. K. Khurana, J. Indian Chem. Suc., 1969, 46, 505. L. Crombie, C. F. Doherty, and G. Pattenden, J . Chem. Suc. (C), 1970, 1076.

178

Organophosphorus Chemistry

/ Ph,PH

Br-

I

(i) NaBH, (ii) Ph$H Br(iii) Base

Ph,P: CH* C0,Me (1 23)

+ Me. C i C. C(SMe) :CH-C i C*CHO

-

Me. Ci C*C(SMe):CH-Ci C. CH: CH*. C0,Me c, t

Ylides and Related Compounds 179 the synthesis of ( f)-steviol methyl ether,64dihydr0-5,6-norcaryophyllene,~~ ( f )-nootkatone,6s ( -)-phyll~cladene,~~ and ( +)-~-cadinene.~~ In the last synthesis, the cis-decalone (1 27) gave the trans-decalin (128), epimerisation via the enol form preceding methylenation. To avoid a similar isomerisation in the synthesis of a racemic boll weevil pheromone, the ketone (129) was added slowly to an excess of the ylide in THF-DMSO (4 : 1); only 3% of the trans-acid was formed.sQ

-( 129)

Me

80%

Among other isoprenoids synthesised using phosphorus ylides are H. cecropia juvenile hormone,70 ( 5 ) - ~ i r e n i n , ~a ~ p e r o n o n e ,(~ ~)-aand 3,4,3’,4’-bi~dehydro-p-carotene.~* (iii) Miscellaneous. ( f)-Dictyopterene A (130) was obtained as together with an equal amount of the cis-isomer. Girinimbine (131) was synthesised 76 by an application of the procedure of Schwei~er.~? Ylides were also used in syntheses of di-0-methylstrepsilin 78 and of (-)-epiallogibberic acid.7Q

+

64 6s 66

67 68

69

70

71 72 75

74 76 7e

77

78 7g

K. Mori, Y.Nakahara, and M. Matsui, Tetrahedron Letters, 1970, 2411. J. L. Gras, R. Maurin, and M. Bertrand, Tetrahedron Letters, 1969, 3533. J. A. Marshall and R. A. Ruden, Tetrahedron Letters, 1970, 1239. R. A. Appleton, P. A. Gunn, and R. McCrindle, J. Chem. SOC.(C), 1970, 1148. M. D. Soffer and L. A. Burk, Tetrahedron Letters, 1970, 211. R. Zurfliih, L. L. Dunham, V. L. Spain, and J. B. Siddall, J. Amer. Chem. Soc., 1970, 92, 425. G. W. K. Cavill, D. G. Laing, and P. J. Williams, Austral. J. Chem., 1969, 22, 2145. J. J. Plattner, U. T. Bhalerao, and H. Rapoport, J. Amer. Chem. SOC.,1969, 91, 4933. G. Pattenden, Tetrahedron Letters, 1969, 4049. L. Bartlett, W. Klyne, W. P. Mose, P. M. Stopes, G. Galasko, A. K. Mallams, B. C. L. Weedon, J. Szabolcs, and G. Tbth, J. Chem. SOC.(C), 1969, 2527. J. D. Surmatis, A. Walser, J. Gibas, and R. Thommen, J. Org. Chem., 1970, 35, 1053. K. C. Das and B. Weinstein, Tetrahedron Letters, 1969, 3459. N. S . Narasimhan, M. V. Paradkar, and A. M. Gokhale, Tetrahedron Letters, 1970, 1665. E. E. Schweizer, E. T. Shaffer, C. T. Hughes, and C. J. Berninger, J. Org. Chem., 1966, 31, 2907. J. D. Brewer and J. A, Elix, Tetrahedron Letters, 1969, 4139. K. Mori, M. Matsui, and Y. Sumiki, Tetrahedron Letters, 1970, 429.

180

Organophosphorus Chemistry

+ Ph,P:CH.CaHQ

Ether

cC4HQ

+ + Ph,P.CH,*CMe:CH,

C1-

CHO

Me B. Carbohydrates.-Among ylides, Ph3P:CHR (1 32), used in conventional olefin synthesis with protected aldehydu-sugars are those with R = MeYBo BU,~OCH:CH2,81 C H : C H O R ,CHOYB1 ~~ SMe,82 C O . C O , B U ~ ,and ~ ~ the (131)

11%

"k

II 0 (132a) R = H or Ph

(1 33)

CH*SPh

-

D-Arabhose i- Ph,P: CH SPh

DMSO.

11

HgCI,

__j

HgO

2-Deoxy-~-glucose 50%

H+H H OH

Hzo

CH20H

(135)

83

72%

Yu. A. Zhdanov and V. G. Alekseeva, Zhur. obshchei Khim., 1969,39,405. Yu. A. Zhdanov and V. G. Alekseeva, Zhur. obshchei Khim., 1969, 39, 112. J. M. J. Tronchet, N. Le-Hong, and Melle F. Perret, Helu. Chim.Acta, 1970, 53, 154; J. M. J. Tronchet and J. M. Chalet, ibid., p. 364. N. K. Kochetkov, B. A. Dmitriev, and L. V. Backinowsky, Carbohydrate Res., 1969, 11, 193.

Ylides and Related Compounds

181 stable ylides (132a).84 The acetonylidenephosphorane (132 ; R = CO Me) with partially protected 85 and with free aldoses 86 in D M F at 90-100 "C for 30 h gave the expected unsaturated ketones as internal acetals. Under the same conditions the ylide (132 ; R = p-Me0 - C6H, CO) with partially protected aldoses gave either furans, e.g. [(133); 13x1 from 3-0-methylglucose, or anhydro-derivatives with y- or &oxide rings, e.g. l(134); 11x1 from 3-0-benzylglucose.87 The ylide (133; R = SPh) with unprotected aldoses in DMSO gives unsaturated thioethers in high yields,88e.g. (135) from D-arabinose, which are readily converted into 2-deoxyaldoses. The protected nucleoside aldehyde (136) on refluxing in ethanolic sodium ethoxide with the salt (1 37) gave the acids (1 38) and (139), together with their (138) and its ester were probably formed by rearrangement of the primary a,P-unsaturated ester, while the other products may have arisen via the cx,p-unsaturated aldehyde.

-

-

0

-t

OH

C. Miscellaneous.-Full details have appeared of the self-condensation of the ylide from the salt (140). Minor products such as (141) and (142) can be rationalised in terms of the formation of acetaldehyde and 5-methylfurfuraldehyde as shown. The dibenzocyclo-octatetraene (144) and the tribenzo-[ 12lannulene (145) were isolated 91 from the self-condensation of the ylide from the salt (143) but no dimer of benzocyclobutadiene, which would result from intramolecular olefin synthesis, was detected. Among olefins prepared by methylenation are (146) 92 and (147).93 f4 85

86

ns 8''

so O1

g2

O3

R. E. Harmon, G. Wellman, and S. K. Gupta, Carbohydrate Res., 1969, 11, 574. Yu. A. Zhdanov and V. A. Polenov, Zhur. obshchei Khim., 1969,39, 1124. Yu. A. Zhdanov and V. A. Polenov, Zhur. obshchei Khim., 1969, 39, 1121. Yu. A. Zhdanov and V. A. Polenov, Zhur. obshchei Khim., 1969, 39, 119. H. J. Bestmann and J. Angerer, Tetrahedron Letters, 1969, 3665. P. Howgate, A. S. Jones, and J. R. Tittensor, Carbohydrate Res., 1970, 12, 403. J. A. Elix, Austral. J. Chem., 1969, 22, 1951. C. Brown and M. V. Sargent, J . Chem. SOC.( C ) , 1969, 1818. A. P. Krapcho and D. E. Horn, Tetrahedron Letters, 1969, 4537. J. M. Conia and J. M. Dems, Tetrahedron Letters, 1969, 3545.

7

182

Organophosphorus Chemistry

Me-(-&HO

Me

t CH,.CHO

MeCH:CH

a /

Reflux

-

CH,*PPh,

26.3%

(144)

(143)

+

(145)

+

0.41%

KOBU~ 7

+Ph3P*CH3

PhLi

xH x H2C

(146) 20%

+ Ph,P.CH, +

(Pri),O

NaoPri

(147) 60%

Ylides and Related Compounds

183

The polyenyl-substituted furans and thiophens (148) and (149) have been prepared as A number of aromatic and heterocyclic aldehydes have been condensed Q5 with the ylide from the salt (150), and the aldehydes (1 5 1) gave the corresponding olefins with the ylides (1 52), each vinyl thioether being obtained as geometrical isomers.96 A Wittig reaction between the a-diketone (153) and the bis-ylide (154) gave Q7 benzo[3,4]cyclobuta[1,2-c]thiophen (1 55).

4 Synthetic Applications of Phosphonate Carbanions In benzene, THF, or dimethoxyethane the cyanomethylphosphonate (1 56; R = CN) and aromatic aldehydes in the presence of sodium hydride gave the same thermodynamic mixtures of cis- and trans-olefins, independent of the order of addition of reagents. However, in hexamethyl phosphoric triamide (HMPT), while the thermodynamic mixture was obtained on addition of the aldehyde to the phosphonate in HMPT containing one mole of sodium hydride, a kinetically controlled mixture of isomers resulted from addition of the base to the phosphonate and an excess of aldehyde in HMPT.QS J. W. Van Reijendam, G. J. Heeres, and M. J. Jannsen, Tetrahedron, 1970, 26, 1291. T. R. Pampalone, Org. Prep. Procedures, 1969, 1, 209. u' H. Saikachi and S. Nakamura, Yakuguku Zusshi, 1969, 89, 1446. 97 P. J. Garratt and K. P. C. Vollhardt, Chem. Comm., 1970, 109. J. Seyden-Penne and M. G. Lefebvre, Compt. rend., 1969,269, C, 48. O4

95

Organophosphorus Chemistry

184

Steroidal a-acetoxy-ketones of part structure (157) with the anion from (156; R = CN) gave the nitriles (158), together with the iminolactone hydrochlorides (1 59) derived from the isomeric nit rile^.^^ The same anion reacted with the less-hindered carbonyl of substituted succinirnides to give loolargely the trans-isomers, e.g. (160). ( Et0)ZP( : O ) CH2.R

- Irr" 9

(1 56)

CH,OAc

I

1

6

+ (EtO),P(:O)*CH.CN

O

CH,OAc

THF

(157)

+

(158)

(159)

Ph Me

p0

~

+ (156)

(MeOCH,),. NaH

~

~

I

Me

'

;yJ--N o I Me

H

(160) 46%

+

6% cis

Use of the phosphonate (156; R = SMe) in olefin synthesis lol has been reinvestigated.lo2 Successive treatment of (156; R = SMe) with butyllithium and an alkyl iodide gave the (1 -methylthio)alkylphosphonates (1 6 1). The lithio-derivatives of these reacted with carbonyl compounds to give adducts which decomposed at 50 "C in THF to give substituted vinyl methyl sulphides (162). These are readily converted into ketones on mercury-catalysed hydrolysis. (EtO),P(:O)-CHRl=SMe

(i) BuLi

(EtO),P(:O)-CRl(SMe).C(6)R2R3Li+

(161)

I

i"'" (EtO),PO,- Lif

+ (MeS)RIC:CR2R3 (1 62)

Among other substituted phosphonate esters used in olefin synthesis G . R. Pettit, C. L. Herald, and J. P. Yardley, J. Org. Chem., 1970, 35, 1389. C. Gadreau and A. Foucaud, Compt. rend., 1970, 270, C , 1430. lol M. Green, J . Chem. Soc., 1963, 1324. l o 2 E. J. Corey and J. I. Shulman, J . Org. Chem., 1970, 35, 777. @e

loo

185

Ylides and Related Compounds

were (156; R = CH:CH.CO2Me),lo3 (156; R = S0,Me),lo4 (156; R = a-naphthyl),lo5 (156; R = CO ~C5H11),106 (163),lo7 and (164).lo8 The enamines from the last were readily hydrolysed to a-diketones. Me

I

NaH

(R1O),P( :0)-CH(NR2R3).CO*R4+ R5*CH0 ------+ (164)

-

R5* CH :C(NR2R3) CO R4

I

H+-H20

-

R5*CH2*CO CO * R4

The ambident anions (I 65), formed from y-substituted allylphosphonates, with carbonyl compounds gave the expected olefins (166) via coupling at the a-position when X was OEt, OPh, SPh, or NR2,109but products derived from both a- and y-coupling when X was halogen.llo Only the

.

( Et0)2P( :O).C -C -C X I

I

+

R" CO - R4 *

R3R4C:CH * CR1:CR2X

I

I

X = CI, Br 2 H

R'

R2 R3 I I (Et0)2P(:O)*CH:CH-C-C-R4 \ / 0 (167)

+

(166; X = C1, R1 = H)

+

(1 68) R. S. Burden and L. Crombie, J. Chem. SOC.( C ) , 1969, 2477. Io4 I. Shahak and J. Almog, Synthesis, 1969, 1, 170. I o 5 W. E. Hahn and J. Zimnicki, Roczniki Chem., 1969, 43, 95. l o 6 E. J. Corey, Z. Arnold, and J. Hutton, Tetrahedron Letters, 1970, 307. '07 D. Redmore, J. Org. Chem., 1969, 34, 1420. H. Gross and W. Buerger, J. prakt. Chem., 1969, 311, 395. log G. Lavielle and G. Sturtz, Bull. SOC.chim. France, 1970, 1369. G. Lavielle, Compt. rend., 1970, 270, C, 86. lo3

Organophosphorus Chemistry

186

epoxides (1 67), from y-coupling, and the dihydrofurans (1 68), from a-coupling, were observed in protic solvents. The ambident anion from the allylphosphonamide (169) gave entirely addition to the y-site but that from the cyclic phosphonamide (170) gave with ketones the /3-hydroxyphosphonamides (1 71).ll1 These on heating formed dienes. Both the a-position of the phosphonamide carbanion and the carbonyl group must be unhindered for selective addition to the a-site to occur.

-

CH, :CH CH, * P( :O)(NMe2),

(i) BuLi

(169)

Me,C(OH).CH,-CH:CH.P(:O) (NMe2)2 Me Me

Me

R1R2C: CHCH:CH,

Alkyl-pyrrolones (172) were obtained on intramolecular condensation of the phosphonates (173) prepared as shown.l12 The dihydropyridone (1 75) was similarly obtained starting from diacetoneamine (1 74), but N-ethyldiacetoneamine could not be condensed with the acid-phosphonate. R2-C(OEt), I

R3-C

/ \

R4 NH2

ll1 112

+

R’ I HC-P(:O)(OEt)Z I C02H

-

R1 R2-C(OEt),

I

( 173) E. J. Corey and D. E. Cane, J . Org. Chem., 1969,34, 3053. G. Stork and R. Matthews, Chem. Comm., 1970, 445.

1

HC-P( :O)(OEt),

I

c=o

Ylides and Related Compounds

187

M e y o NH,

+ H02C*CH,*P(:O)(OEt)2

Me &Me

(174)

Me M

eH

60

(1 75)

Benzylideneaniline and the phosphonate (1 76) in the presence of sodamide gave the kinetically-controlled erythro-isomer of (1 77) in ether at - 33 "C but the thermodynamically-controlled threo-isomer in ether at + 10 "C or in liquid ammonia.l13 p-Me.C,H,-CH,.P(:O)(OEt),+ C,H,.CH:N-Ph (1 76)

NaNHn

PhCH(NHPh). CHAr[P( :O)(OEt),] (177)

5 Ylide Aspects of Iminophosphoranes The sulphonyliminophosphoranes (1 78) have been obtained 114 by heating with copper powder the adducts from phosphines and NN-dichlorosulphonamides.

+

-

Ar-SO,-NCI, R3P R = Bu or Ph

[I

-----&+ Ar.SO,-N:PR, (178)

Iminotriphenylphosphorane (1 79) reacts exothermically with nitriles to give the stabilised iminophosphoranes (1 80). Other reactions of (1 79) leading to stable phosphoranes are given in the formulae.lls Tetrazoles (182) are formed when the iminophosphoranes (181; R1 = a-naphthyl, /I-naphthyl, Ph, Ph CH, * CH,, or a-pyridyl) are treated either with an acyl azide or with an acyl chloride followed by sodium azide.l16 Only when trifluoroacetic anhydride was used was the imine (183) isolated. The iminophosphorane (1 79) with acyl azides gave the acyliminophosphoranes (184). No tetrazoles were obtained from the iminophosphoranes 113 114 116

116

M.Kirilov and J. Petrova, Tetrahedron Letters, 1970, 2129. A. Schonberg and E. Singer, Chem. Ber., 1969, 102, 2557. A. S. Shtepanek, E. N. Tkachenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 1475. E. Zbiral and J. Stroh, Annalen, 1969, 725, 29.

Organophosphorus Chemistry

188

T

-

RCN R = Ph, CCI,, CF,, etc.

Ph,P:N*CO-CF, <

CF,. CO,Et

Ph3P:NH

72%

(179)

BrCN

Ph,P:N.CN

or PhOCN

53%

.

Ph3P:Nu C(: NR2).R1

Ph3P :N C( :NH) * CF,

(181 ; R1 = SiMe,, CH,OMe, Pr*, or But). The iminonitriles (185) are formed from the iminophosphoranes (181) and acyl cyanides but not from the acylated iminophosphoranes and potassium cyanide.

Ph,$ *NR1.CO *R2 C1-

p-

Ph3h-NR1-C(0)N,-R2+------

(181)

+

R2-C0.N3

l-ph:,po\ R1-N-C-R2 I \ \ N k /N N (182)

2Ph3P:NH

25--69%

+ R-CO-N,

+

Ph,P.NH, N3-

(179)

+ Ph,P:N*CO-R (1 84)

Pyrazines (186) are produced 11' in 35-4574 yield when a-azidoketones are refluxed in benzene with triphenylphosphine, presumably via inter117

E. Zbiral and J. Stroh, Annulen, 1969, 727,231.

Ylides and Related Compounds

189

molecular condensation of the intermediate iminophosphoranes. Intramolecular condensation of the iminophosphorane from a 8-azidoketone was used in a rather neat synthesis 11* of nigrifactin (187). R1.CH(N,).CO-R2+Ph,P

R1(R2*CO)CH*N:PPh3

I

- Ph3PO

&=+&

N3

(187)

The trimethylsilyliminophosphorane(1 89) with chlorodiphenylphosphine gave 119 the bis(dipheny1phosphino)aminophosphonium salt (1 88) which on heating at 210 "C in U ~ C U Ogave the iminophosphorane (190) and chlorodiphenylphosphine. The last reaction was reversed at room temperature. The dissociation products were trapped as sulphides on refluxing the salt (188) in benzene with sulphur. Ph3PBr,+ (Me,Si),NH

Ph3$.N(PPh,)2

Ph3P:N -PPh,

+

-

CI-

MeCN

Ph3$ .N H * SiMe, Br -

Ph,PCl 4

Ph,PCl

IF:;+

Ph,P:N-SiMe,

Ph,P :N -P(:S)Ph,

+

Ph,P( :S)Cl

(190)

Studies on the basicity and structures of the iminophosphoranes (191) and (192) have been reported.120 118 119

12"

M. Pailer and E. Haslinger, Monatsh., 1970, 101, 508. H. G. Mardersteig, L. Meinel, and H. Noth, 2. anorg. Chem., 1969, 368, 254. T. G . Edel'man and B. I. Stepanov, Zhur. obshchei Khim., 1969, 39, 712, 713.

190

Organophosphorus Chemistry R*C,H,*PEt,:N*C,H,*NOB

PhPEt,:N

(191)

0 \

NEPPhEt,

(192)

The interesting iminodiphosphine (193) 121 with chlorodiphenylphosphine and with methyl iodide gave the salts (194) and (195) respectively.122 With sulphur the monosulphide (196) and, under more forcing conditions, the disulphide (1 97) were formed.

+

Ph,P.PPh,.N. PPhzaPPh, C1-

PhzPCI

Ph,P * PPh2:N * PPh,

1

+

Ph,P-PPh,.N.PPh,Me I(195)

R.T.

PhzP PPh, :N P( :S)Ph2 6

(196) lZ1

Me1

(193)

S-CsH

-

--

Reflux

Ph2P(:S) PPh, :N * P( :S)Ph,

€1. Noth and L. Meinel 2. anorg. Chem., 1967, 349, 225. L. Meinel and H. Noth, 2. anorg. Chem., 1970, 373, 37.

(197)

9 Phosphazenes BY R. KEAT

1 Introduction

During the past year, an increasing emphasis on the synthesis and properties of acyclic phosphazenes has been apparent in the literature. The detailed molecular structure of a monophosphazene, FPh,P=NMe, has been reported for the first time and the P=N-C unit shown to be non-linear, as anticipated from the presence of a lone pair on the nitrogen. Further insight has been gained into the mechanisms underlying the formation of cyclic phosphazenes,2 and many reports of the physical properties of this latter group of compounds have been made. An introductory account of the chemistry of cyclophosphazenes (phosphonitrilic compounds) has been published3 as well as a review of fourmembered ring

compound^,^ many of which may be considered as dimeric phosphazenes. The chemistry of polymeric phosphazenes has been reviewed in detail.s

2 Synthesis of Acyclic Phosphazenes A. From Phosphorus Amides.-By careful experimental work it has been shown that phosphorus pentachloride and liquid ammonia give an aminophosphonium salt at - 70 "C: PCl,

+ 8NH3

[(H,N),P]+Cl-

+ 4NHdCI

This salt is surprisingly thermally stable, decomposing at 200 "C, so that the ammonium chloride may be removed by sublimation, but in the G. W. Adamson and J. C. J. Bart, Chem. Comm., 1969, 1036; J. Chem. SOC.(A), 1970, 1452.

a

A. Schmidpeter, C. Weingand, and E. Hafner-Roll, 2. Naturforsch., 1969, 24b, 799. R. H. Cragg, Essays in Chemistry, 1970, 1, 77. M. Becke-Goehring, Chem.-Ztg, 1970, 94, 179. V. V. Kireev, G. S. Kolesnikov, and I. M. Raigorodskii, Russ. Chem. Rev., 1969,38,667. A. Schmidpeter and C. Weingand, Angew. Chem. Internat. Edn., 1969, 8, 615.

192

Organophosphorus Chemistry

presence of a base (in this case, diethylamine = B) condensation occurs to give a known diphosphazadiene : [(H2N)4P]fC1-

+B

+ NH3 + BHCl

[(H,N)3P=N-P(NH2)3]+Cl-

-

With phosphorus pentachloride, the aminophosphonium salt undergoes a normal Kirsanov reaction : [(H,N),P]+Cl-

+ 4PC1,

[(C13P=N),P]+C1-

+ 8HC1

This reaction may be contrasted with the one-step ammonolysis of phosphorus pentachloride under more forcing conditions,, where linear and cyclic phosphazenes are formed and where chain branching is unfavourable because of a deficiency of P-NH, functions at lower NH3 : PC15 ratios and a deficiency of PCl functions at higher NH3 : PCl, ratios. At ambient temperatures, the ammonolysis of dialkylaminotetrachlorophosphoranes, R,NPCl, (R = Me, Et, or Bun) has been shown to lead to diphosphazadienes :, 2R,NPCl,

+ 12NH,

---+ [R2N(HzN),P=N-P(NH2),NR,I+CI-

+ 7NH4Cl

However, with bis(dialky1amino)trichlorophosphoranes the general tendency to condensation is reduced and tetra-aminophosphonium salts are first isolated : (R,N)2PCI3

+ 4NH3

+

2NH4Cl [(RzN)J'(NH,),]+Cl(R = Me, Et, or Bun)

Condensation products, e.g. [(R2N),(H2N)P=N -P(NR2)z(NH2)]+Clhave also been identified in these cases and when R = morpholino. Only in the case of dimethylaminotetrachlorophosphorane was condensation beyond a diphosphazadiene observed, and in this case a triphosphazene of structure (1) was possibly formed, which cyclised to give (2) as a mixture of geometrical isomers. NMe, NMe, NMe, I I I H,N- P=N-P=N-P-Cl I I I c1 c1 c1 (1)

-

"Me,

C1/

(2)

Many examples of the Kirsanov reaction continue to be reported: RNH,

+

+

PC1,XYZ RN=PXYZ 2HC1 (See Table for details of R,X, Y, and Z.)

These reactions were, in general, carried out in warm carbon tetrachloride solution and the products appear to be monomeric in solution, consistent with earlier suggestions that compounds of the type, R3P=NR1, are

' lo

H. H. H. H.

W. W. W. W.

Roesky and L. F. Grimm, Chem. Ber., 1969, 102, 2319. Roesky, Chem. Ber., 1970, 103, 694. Roesky and E. Niecke, 2. Naturforsch., 1969, 24b, 1101. Roesky and W. Grosse-Bowing, 2. Naturforsch., 1969, 24b, 1250.

PSCl,* F F c1 7

PSFz F F C1 7

C1 CCl,

8

C1 Me

8

PSC1, Cl c1 Ph 7

c1

c1

PSCl, c1 c1 Me 8

PSF,

PSFZ

discussed in ref. 11.

PSCI,* F F F 7

R X Y Z Ref.

* n.m.r.

PSF,* F F F 7

R X Y Z Ref.

Table RN=PXYZ Compounds

7

PSCl, c1 Ph Ph

PSF, Cl C1 Ph 7 PSCl, Ph Ph Ph 7

PSFZ C1 Ph Ph 7 POF, C1 C1 C1 9

PSF, Ph Ph Ph 7

8

POF, C1 C1 CCl,

7

PSFCl* F F F

POFCl c1 c1 c1 9

PSFCl F F c1 7

CCl, 8

c1 8

POFCl c1

8

c1 CCl,

c1

PSFCl

POFCl c1 Cl Me

8

c1 Me

PSFCl Cl

8

POCl, c1 c1 CCl,

PSFCl c1 CI Ph 7

10

N,P,F, F F F

PSFCl CI Ph Ph 7

EtPSF c1 c1 c1 10

PSFCl Ph Ph Ph 7

194

Organophosphorus Chemistry

expected to be monomeric when R1is an electron-withdrawing substituent. In all cases lH and l9F n.m.r. and i.r. data were reported and the latter discussed. The P-F spin-spin coupling constants of compounds marked with a star have also been compared with related values for mononuclear phosphorus compounds.11 An interesting rearrangement of a monophosphazene is thought to occur following the reaction of PP-diethylphosphinic amide with phosphorus pentachloride,12 which does not give the expected trichlorophosphazenyl derivative, Et2P(:0)*N=PC13: Et,P(: O).NH,

+ PCI,

Et,P(CI)=N*P(: O)C1,

+ 2HCl

The same product was also obtained from the reaction of Et2P(:O).NC12 with phosphorus trichloride, a reaction expected to give the trichlorophosphazenyl derivative, Et2P(:0) N=PC13, with the elimination of chlorine. Evidently, the rearrangement :

-

is facile at ambient temperatures, and it was suggested that it may be intermolecular.

-

B. From Carbon Amides.-Several examples of amino-triazines have been employed as'substrates for the Kirsanov reaction :13 R.NH2

+ Ph,PCl,-,

R-N=PCI3-,Ph,

+ 2HC1

c1-

'C=N

Fi

N=PPh, I H2NCkN,kNH2 I

l1 la

l3

E. Fluck and G. Heckman, 2. Nuturforsch., 1969, 24b, 953. A. Ya. Yakubovich, I. M. Filatova, E. L. Zaitseva, and A. P. Simonov, Zhur. obshchei Khim., 1969, 39, 2213 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 21611. H. W. Roesky and H. H. Giere, Chem. Ber., 1969, 102, 2330.

195

Phosphazenes

However, reaction with C12PF3gives RN=PFC12, a result which may be contrasted with that obtained for the cyclophosphazene in the Table. An extensive series of phosphazenyltriazine derivatives have been isolated from the reaction of melamine (4) with a tertiary phosphine R3P (R = Ph, Bun, or C,H,,) and chlorine:14 (4)

+

Ph,P

+

C&

172 "C

'(5)

The tris(triphenylphosphazeny1)-derivative, C,N, (N=PPh3)3 was obtained by deprotonation of (6) with sodamide in liquid ammonia. N-Trichloromelamine, C,N,(NHCl), or N-hexachloromelamine, C3N3(NC12)3,and R3P generally gave a series of aminophosphonium salts and phosphine adducts, but (7) has also been reported from the latter reaction and is of interest as a fungicide.16 The reactions of C-trifluoromethyl-substitutedanilines, RNH, [R = (8)-( 1 l)], with phosphorus pentachloride have been investigated.16 As

(9)

expected, the nature of the R group can affect the position of the equilibrium for the products of these reactions:

Molecular weight measurements in benzene solution and 31P n.m.r. studies showed that when R = (8), the phosphazene was monomeric, but when R = (9) or (10) dimers were present. A mixture of monomers and dimers was observed when R = (11). Here, also, the position of the equilibrium appears to be dominated by the base strength of the nitrogen atom. However, the effect of different phosphorus substituents on the equilibrium is l4 l5 le

G. Gotsmann and M. Schwarzmann, Annalen, 1969, 729, 106. Badische Anilin und Soda Fabrik A.G., Fr. Dernande, 2,001,704 (Chem. Abs., 1970, 72, 66,992). M. Bermann and K. Utvary, Munatsh., 1969, 100, 1041.

196

Organophosphorus Chemistry

not clear, because Ph,P(F)=NMe is monomeric in solution17 and in the solid state,l whereas Ph,P(Cl)=NMe is dimeric in methylene chloride.l* The Kirsanov reaction proceeds normally with an extensive series of 2- and 4-aminopyridines to give trichlorophosphazenyl-derivatives of structures (12) l9 and (13) 2o respectively (R', R2, and R3 were various alkyl-, aryl-, or halogeno-substituents). Compounds of structure (12) were identified as their PP-bis(morpho1ino)-derivatives.

R'

N=PC13

(1 2)

(1 3)

Diphenyltrichlorophosphoraneundergoes reactions with methylamine or aniline hydrochlorides to give aminophosphonium salts :21 PhZPCl3

+ RNfH,C1-

[Ph2PCl.NHRlfC1(R = Me or Ph)

+ HCl

Further heating of the N-phenyl salt gives Ph,P(Cl)=NPh, which is monomeric in benzene solution. Heating a 2 : 1 molar ratio of Ph2PC13 and MeNH3Cl- at 200 "C gives the known salt, [Ph2P(Cl).N=PPh2Cl]+Cl-, with the elimination of hydrogen chloride and even methyl chloride. Phosphazenes obtained by the reaction of alkyltetrachlorophosphoranes with methyl carbamate are thermally very unstable 22 and may decompose in two possible ways: MeO-COaNH,

+

RPC14

l/n(ROCN),

-+

+

[MeO-CO-N=PCl,R]

RPOCl,

RCI

+ RP(O)Cl*NCO

When R = CH2Cl, route b is favoured, whereas previous results have shown that when R = Me, route a is favoured. The phosphazenes obtained from the reaction of dialkylcyanoacetamides with phenyltetrachlorophosphorane are, however, comparatively thermally stable :23 l7

2o

21 22

23

C. Brown, M. Murray, and R. Schmutzler, J. Chem. Soc. (C), 1970, 879. P. B. Hormuth and H. P. Latscha, 2. anorg. Chem., 1969, 365, 26. N. V. Sazonov and A. A. Kropacheva, Khim. geterotsikl. Soedinenii, 1970, 55 (Chem. A h . , 1970, 72, 1 1 1,393). A. F. Pavlenko, V. P. Akkerman, G. A. Zalesskii, and Y . N. Ivashchenko, Zhur. obshchei Khim., 1969,39, 1516 [ J . Gen. Chem. (U.S.S.R.), 1969, 39, 14861. W. Haubold and M. Becke-Goehring, Z . anorg. Chem., 1970,372, 273. V. A. Shokol, V. F. Gamaleya, and G. I. Derkach, Zhur. obshchei Khim., 1969, 39, 1703 [ J . Gen. Chem. (U.S.S.R.), 1969, 39, 16691. V. I. Shevchenko, M. Evdik, and A. M. Pinchuk, Zhur. obshchei Khim., 1969,39, 1514 [ J . Gen. Chem. (U.S.S.R.), 1969, 39, 14831.

197

Phosphazenes

+ 2HC1

R,C(CN)*CO*NH,+ PhPCl, R,C(CN)CO-N=PPhCl, (R = Me, Et, Pr”, Bun or amyl)

The reaction of oxamide, (CONH,),, with phosphorus pentachloride has been reinvestigated 24 and shown to give compounds (14) and (15), rather than monocyclic products with structures related to the ring system (16) previously suggested. CIC -CCI, I1 I N\ CI,P\/N, PCI, N’ \N

c1,c-CCI, I I HN N c c p < ‘PCl, N/ \NH

I

CI,C-CC12

I

t

F-c\N

N ‘P’

II

CI 2 c-CCI

(16)

C. From Sulphur Amides.-A number of sulphur(v1) amides react with phosphorus(v) halides to give monomeric phosphazenes :

-

+ PF,Cl, FSO,NH, + PCl, FSO,NH, + Ph2PC13 ----+ CF,SO,NH, + PCl, PhS02NH2+ Ph,PCl, -----+ ClSO,NH,

+ 2HC1 FSO,.N=PCl, + 2HC1 FSO,*N=PClPh, + 2HC1 CF3S0,.N=PCI, + 2HC1 PhSO,.N=PClPh, + 2HC1 C1SO2-N=PF3

(ref. 25) (ref. 26) (ref. 26) (ref. 27) (ref. 26)

It is of interest that NN’-dimethylsulphamide, S02(NHMe)2,also reacts with phosphorus pentachloride to give (1 7) in good yield :28 SO,(NHMe),

+ 3PC1,

(17)

+ SOCI, +

POCl,

+ C1, + 2HC1

(18)

-

However, in the presence of pyridine, the sulphur-nitrogen bonds are retained and compound (18) is obtained: 2SO,(NHMe), 24

25 26

27 28

+ PCl, + 4NC,H,

(18)

+ + 4NHC,H,Cl-

M. Becke-Goehring and M. R. Wolf, 2. anorg. Chem., 1970, 373, 245. H. W. Roesky and W. Grosse-Bowing, Inorg. Nuclear Chem. Letters, 1969, 5 , 597. S. Kongpricha, U.S.P., 3,445,513 (Chem. A h . , 1969, 71, 50,218). H. W. Roesky, G. Holtschneider, and H. H. Giere, Z. Naturforsch., 1970, 25b, 252. M. Becke-Goehring and H.-J. Wald, Z. anorg. Chem., 1969, 371, 88.

Organophosphorus Chemistry

198

D. From Silicon-Nitrogen Compounds.-The cleavage of silicon-nitrogen bonds by phosphorus(v) halides can provide a useful route to phosphazenes : F,P(:X)NH.SiMe, FClP(:X)NH.SiMe,

+ PCI, + PCI,

-

+ HCl + Me,SiCl

CI,P=N-P(:X)F,

+

+

Cl,P=N.P(:X)FCl HCl Me,SiCl (X = 0, ref. 29); (X = S, ref. 30)

The intermediates, phosphinylsilylamines or phosphinothioylsilylamines, are readily obtained by reaction of the appropriate phosphorus(v) halide with hexamethyldisilazane, e.g.

-

@ ,

P(:O)F,

+ (Me,Si),NH

+ Me,SiCl

F,P(:O)NHSiMe,

The same disilazane also reacts with dibromotriphenylphosphorane to give 31 an aminophosphonium salt, which can be deprotonated by triethylamine leaving an N-silylphosphazene, Ph,P=NSiMe, : Br,PPh,

+ (Me,Si),NH

-40

"c> [Ph,P.NHSiMe,]fBr-

MeCN

-

+ Me,SiBr

The same final product can be obtained by refluxing the reaction mixture in benzene solution : 2Ph,PBr2 + 2(Me3Si)NH

Ph,P=NSiMe,

+ [Ph,PNH,]+Br- + 3Me,SiBr

Addition of chlorodiphenylphosphine to this N-silylphosphazene gave a linear diphosphazene salt which, on heating, gives a new N-diphenylphosphino-derivative : Ph,P=N. SiMe,

+ 2ClPPh2

[Ph3P-N=PPh2PPh2]+C1-

1

+ Me,SiCl

180-210 O C

Ph3P=N-PPh2

+ ClPPh,

The linear structures of the salt and of its pyrolysis product were established by 31Pn.m.r. The latter compound was characterised by a relatively large P-N-P spin-spin coupling constant (93.4 Hz). In contrast, fluorophosphoranes and disilazanes do not lead to N-silylphosphazenes :17 Ph,PF, 20

so a1

+ PhN(SiMe,),

Ph,P(F)=NPh

+ 2Me,SiF

0. Glemser, U. Biermann, and S. P. von Halasz, Inorg. Nuclear Chem. Letters, 1969, 5 , 501. 0. Glemser, U. Biermann, and S. P. von Halasz, Inorg. Nuclear Chem. Letrers, 1969,5, 643. H. G. Mardersteig, L. Meinel, and H. Noth, 2. anorg. Chem., 1969, 368, 254.

Phosphazenes

199

As stated, the product in this case was monomeric. The tautomerisation of some phosphinosilylamines also offers a route to monophosphazenes 32 and, at the same time, provides a new method of forming P-P, P-As, or P-Sb bonds : But,PNH-SiMe,

BunLi

But2PNLiSiMe, + BunH (X = P, As, or Sb)

I

Me2XCl

But,(Me2X)P=NSiMe,

+ LiCl

It is possible that the N-lithiated amine may also partly exist as its tautomer, but this point was not investigated. Further examples of phosphazene synthesis by reaction of aminophosphines with carbon tetrahalides have been reported:

ButP(NH.SiMe3)R

+ CC14

-

c1 I

+ CHCI, (ref. 33)

But-P=N.SiMe,

I

R (R = NHeMe, NH-SiMe,, or NMeaSiMe,)

Cl ButP(NH.SiMe3),

+ CC14

----+

I

+ CHCI, (ref. 34)

But-P=N-SiMe,

I

N H .%Me,

Structures were established by lH n.m.r. spectroscopy, which also showed 33 that in some cases there was rapid (on the n.m.r. time-scale) intramolecular ligand transfer between the nitrogen atoms at 35 “C [e.g. as in (19) and (20)l. Me

(19)

(20)

E. Other Methods.-It has been recognised for some time that an equilibrium involving phosphorus(I1r) and phosphorus(v) compounds is possible for aminophosphines, e.g. X,P--NHY s2 33 34

7 X2HP=NY

0. J. Scherer and W. M. Jansen, J . Organometallic Chem., 1969, 20, 111. 0. J. Scherer and P. Klusmann, 2. anorg. Chem., 1969, 370, 171. 0. J. Scherer and W. Gick, Chem. Ber., 1970, 103, 71.

200

Organophosphorus Chemistry

Until recently, only the aminophosphine form had been detected, but it has now been shown3, that substituents capable of increasing the base strength of the phosphorus atom and decreasing the base strength of the nitrogen atom can drive the equilibrium to the right. Thus, in compounds with X and Y substituents: X = NMe,

Y

= S0,CGH4Me-p

NMe,

NMe,

NMe,

P(: S)(OPh),

P(: O)Ph,

P(: S)Ph2

-

[prepared, e.g. (Me,N),PCl

+ NaNHSO,C,H,Me-p

Me SO,C,H,Me-p

(Me,N),P(H)=NSO,C,H,Me-p

+ NaCl]

strong i.r. absorptions characteristic of P-H and P=N groupings are observed as well as large P-H spin-spin coupling constants (5O(t-600 Hz) in the lH and 31Pn.m.r. spectra. Phosphorus(v) halides also react with a number of nitrogen compounds other than amides to produce trihalogenophosphazenyl derivatives, e.g. : FS0,NSO

+ PBr,

+

3PC15

MeCN

-

FS02N=PBr3

+ SOBr,

N=PC13

+ ClHC=C<+

PC1,-

PC13

+

CHZCICN

20 "C

~

3PC15 + Cl,C=C,+

k

+

N=PC13 PC13

PCl,-

(ref. 36) 2HC1

+

(ref. 37)

2HC1

(ref. 37)

warm

H,

,c=c,

c1

,N=PC13 Cl

-

+

HCI

(cis and trans isomers)

C1,CHCN

+ PCl,

Cl,C=CClN=PCl,

+ HCl

(ref. 37)

2,2-Dialkylsuccinonitriles are also found to give trichlorophosphazenyl derivatives38 but, concurrently, a pyrrolic ring system is formed: RR1C-CH2

I

t

+ 3PC1,

2HC1 + 2PCl,

+ (21) + RR1C(CN)CC12CN

CNCN (R = alkyl; R1 = alkyl or aryl) 36 36 37

38

A. Schmidpeter and H. Rossnecht, Angew. Chem. Internat. Edn., 1969, 8, 614. H. W. Roesky, 2. anorg. Chem., 1969, 367, 151. H. P. Latscha, W. Weber, and M. Becke-Goehring, Z. anorg. Chem., 1969, 367, 40. V. I. Shevchenko, V. P. Kukhar, and N. R. Litovchenko, Zhur. obshchei Khim., 1969, 39, 2203 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 21521.

Phosphazenes

201 RR'C- CCI I \,"a C'CkNF, N=PC13

(21)

A new route to monophosphazenes has been established by the reaction of a sulphonyl isocyanate with a phosphine oxide:3g

The product was isolated as its anilino-derivative. The rearrangement of bis(dipheny1phosphino)amines on chloroamination 40 provides a route to linear phosphazenes:

An interesting feature of this reaction is the apparent methyl-group migration, whose mechanism has yet to be established. Variations on the azide synthesis continue to be reported:

+

Et2PC6H4X-p+ NSCGH4NO2-p

p-XC,H,P(Et,)=N* CsHaN02-p NZ (ref. 41)

(X = Cl, Me, NMe,, OMe, or C02Me)

Ph3P

+

NaR

b

X

_f

Ph,P=N

X

+

N2 (ref. 42)

K=H C1 Me H H H X = CHO CHO CHO COMe CO-Ph C0.C,H4-p-N=PPh, N-Substituted phosphazenes may also be obtained from the reaction of diazo-compounds with triphenylphosphine: RO)2P(:O)CHN2 + PPh3

98 *O

41

42

43

44

(RO),P(: O)CH=N-N=PPhB (R = Me, ref. 43) (R = Et, ref. 44)

H. Hoffmann, H. Forster, and G. Tor-Poghossian, Monatsh., 1969, 100, 311. D. F. Clemens, M. L. Caspar, D. Rosenthal, and R. Peluso, Inorg. Chem., 1970, 9, 960. T. G. Edel'man and B. I. Stepanov, Zhur. obshchei Khim., 1969,39,714 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 6811. I. N. Zhmurova, A. A. Tukhar', and R. I. Yurchenko, Zhur. obshchei Khim., 1969,39, 2201 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 21501. D. Seyferth and R. S. Marmor, Tetrahedron Letters, 1970, 2493. M. Regitz and W. Anschiitz, Annalen, 1969, 730, 194.

Organophosphorus Chemistry

202

3 Properties of Acyclic Phosphazenes A. Chemical.-The reactivity of a number of nucleophiles towards halogenomonophosphazenes has been studied. Derivatives of the type, F,P=N.P( :S)XX1(X = X1 = F ; X = F, X1= C1; X = X1= Cl), undergo preferential reaction at the F,P= group with silicon-nitrogen compounds :45 XX1P(:S)N=PF3

x = X1 = F;

+ Me,SiR

-

XXIP(S)N=PF,R

R = NMe,, NCS, N=C=NSiMQ,

+ Me,SiF

NMe-SiMe,, or NH-SiMe,

X = F, X1 = Cl; R = NMe, or NH-SiMe, X = xl = C1; R = NMe, or NH-SiMe,

Reaction of F,P(:S)N=PF,R (R = NMe,) with a second mole of silylamine also took place at the same position to give, e.g. F2P(:S)N=PF(NMe,),. Hydrogen bromide effected preferential cleavage of the P-NMe, bond in the mono-dimethylamino-derivatives, leaving new mixed halogenophosphazenyl derivatives: XXIP(: S) * N=PF,NMe2

+ 2HBr

-

XXIP(:S).N=PF,Br (X = X1 = F; X = F, X1 = C1)

+ + NH,Me,Br-

Also, the trifluorophosphazenyl derivative, FClP( :S)N=PF,, gave FCl( :S) .N=PFCl, on treatment with excess dichlorotrifluorophosphorane, C12PF3. This result resembles that already noted for the triazine derivative, C,N3F,(N=PF3).10 It has been suggested46that some of the above halogenophosphazenes may be applied to the synthesis of linear phosphazene chains: FXP(:S).N=PF,

+ (Me,Si),NH

-

FXP(:S)-N=PF,.NH.SiMe, FXP(:S).N=PF,.NH.SiMe,

+ PCI,

FXP(:S).N=PF,.N=PCI, (X = F or C1)

+ Me,SiF

+ Me3SiC1 + HCl

The next -N=PCl, unit could then be introduced by reaction with hexamethyldisilazane and phosphorus pentachloride respectively. Several amino-derivatives of the monophosphazene, PhN=PCl, NEt2, have been prepared :47 PhN=PC12NEt,

+

2R2NH

/

NEtz

+ PhN=P:NRz

+

4-

R2NH2Cl-

C1

45 46

47

H. W. Roesky and L. F. Grimm, Chem. Ber., 1970, 103, 1664. H. W. Roesky and L. F. Grimm, Angew. Chem. Internat. Edn., 1970, 9, 244. M. Bermann and K. Utvary, Monatsh., 1969, 100, 1280.

203

Phosp hazenes

Alkaline hydrolysis of these aminophosphazenes gave the phosphine oxides, PhNHP( :O)(NEt,)NR,, rather than the isomeric phosphazenes, ,NEt, PhN=P\NR, OH

The new ring compound (22) has been obtained 48 from the reaction of the trichlorophosphazenyl derivative ClSOzN=PC13 with trifluoroacetic acid : 4ClSOZN=PCl,

+ 2CF3COzH

___f

+

+

+

(22) SOzClz HN(SO2CI)z 4POC1,

The NH-proton in (22) is acidic, and may be replaced in reactions with Ph4P+C1- and Ph4As+C1-to give salts such as (23).

H

(22)

The dimer (MeNPCl,), reacts with chromium hexacarbonyl in refluxing It seems likely that the lone benzene giving C~S-(M~NPC~,)~C~(CO)~.~~ pairs of electrons on the nitrogen atoms are involved in bonding to the metal. Thermal degradation of the complex yields a polymer (Cr,P5N2)%. The same dimer has also been shown 5 0 to give compound (24) on reaction with two moles of NN’-dimethylurea and compound (25) with methyl isocyanate.18 However, the phenylated dimers (Cl,PhPNMe),, M e c 1 Me Me IN\ /N\bN\ P co Me

MeCl Me (24)

0% ,c1 P

MeNO Y M e

I

oc, N/CO Me

(25)

(ClPh,PNMe),, and the monomer Ph,P=NMe gave the phosphine oxides C12PhP0, ClPh,PO, and Ph3P0 respectively, on reaction with methyl isocyanate. The basic properties of the monomer, PPP-triphenylphosphazene,have been explored :sl 48 49

51

H. W. Roesky, Angew. Chem. Internat. Edn., 1969,8, 510. H.-G. Horn and M. Becke-Goehring, Z . anorg. Chem., 1969,367, 165. M.Becke-Goehring and H. Schwind, 2. anorg. Chem., 1970,372,285. A. S. Shtepanek, E. N. Tkachenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1969, 39, 1475.

204

Organophosphorus Chemistry

e.g. P$P=NH

+ RCN + ROCN

+ RS(: O)(=NR1)Cl + RC(=NR1)Cl + RC(:O)OR1

___j

Ph,P=NC(=NH)R

+ PhOH Ph,P=NH,CI + RS(: O)(=NR1)N=PPh, Ph,P=NH,Cl + Ph,P=NC(=NR1)R Ph,P=N-C(:O)R + R'OH

------+ Ph,P=NCN

___j

(R and R1are various alkyl and aryl substituents.) Reports of the novel properties of triorganoaluminium adducts of monophosphazenes continue. Toluene is eliminated 51a when tri-ptolyl-aluminium or -gallium adducts of N-silylphosphazenes are heated, showing that the aluminium-aryl bond, rather than the phosphorus-aryl bond, is cleaved: Ph,P=N(SiMe,)AI (C,H,Me-p),

In agreement with this suggestion, benzene is eliminated when the adduct (p-MeC,H4),P=N(SiMe,),AlPh, is heated under the same conditions. Trirnethylgermyl adducts of similar structure have also been obtained : 51b R,P=NGeMe,

(R = Me; (R

=

Et;

+ Me,M,OEt,

M = Al, Ga, or In)

-

R,P=N(GeMe,)MMe,

+ Et,O

M = Al, Ga, or In)

However, attempts to obtain analogous N-trimethyltin adducts resulted in spontaneous elimination of tetramethyltin to give phosphazenylsubstituted ring compounds : 2Me,M,0Etz

+

- 2Et,0

+

< 25 "C

2R,P=N. SnMe,

25 "C

R,P=N,

2R3P=N (SnMe3). MMe3

+ (R

=

Me;

(R = Et;

Me, /M\ ,N=PR, M Me, 2Me4Sn

M = Al, Ga, or In) M = Al, Ga, or In)

The last reaction shows that Sn-N bonds are more labile than Ge-N bonds with respect to electrophiles. Chlorodiphenylphosphine and methyl iodide readily add to 51a 51b

H. Schmidbaur and W. Wolfsberger, J . Organornetnllic Chem., 1969, 16, 188. W. Wolfsberger and H. Schmidbaur, J . Orgatlometallic Chem., 1969, 17, 41.

Phosphclzenes

205

Ph2P*PPh2=N.PPh2at the N-bonded PI1’ atom to give salts of structure (26).52 Sulphuration also proceeds (initially) at the same phosphorus atom,

-

[Ph2P PPh2:N * ;Ph,R]XR = Ph,P or Me X = C1 or I (26)

but the use of triethylamine (as a catalyst) is necessary to produce the disulphide : Ph2P*PPh,=N. PPh2

SS reflux benzen;

Ph2P*PPh2=N*P(:S)Ph2 Et3N

>

-

-

Ph2P(:S) PPh2=N P( :S)Ph,

These sulphides may also be obtained: (Me,Si),N.P(: S)Ph, + Ph2PCl ----+- Ph2P-PPh2=N.P(:S)Ph, + 2Me3SiC1 [(Ph2P*PPh2)2N]+Cl-+ $SB Ph2P(:S) PPh2=N* P(: S)Ph2 Ph2P(:S)Cl

+

The formation of the >P-P=N-P-S

skeleton is evidently favoured over

the F>N-P-S skeleton, which might be expected from cleavage of Si-N bonds by chlorodiphenylphosphine. Good evidence for the presence of P-P bonds in these sulphides comes from their cleavage by elemental bromine to give BrPh2P=N.P(:S)Ph2 in both cases. P-P bonds were also indicated by 31Pn.m.r. spectra where large P-P spin-spin coupling constants (ca. 250 Hz) were observed. B. Physical.-Reports of several investigations into the electronic effects associated with the =P=N- bond have appeared. The auxochromic action of the Ph,P=N- group in certain dyes suggests that it has a better ability to donate electrons conjugatively to an unsaturated carbocyclic system than a dimethylamino-group.53 From basicity measurements it has been deduced5* that the PhEt,P=N- group is also electron donating to aromatic ring systems. The n-electron distribution in fluorenones (27)

RR1,P=N-N

R = Aryl R1= Aryl or alkyl 52

68

54

L. Meiiiel and H. Noth, Z. anorg. Chem., 1970, 373, 36. I. N. Zhmurova, Yu. L. Slowinskii, A. I. Tolmachev, and R. I. Yurchenko, Zhur. obshrhei Khim., 1969, 39, 1732 [J. Gen. Chem. (U.S.S.R.),1969, 39, 16971. T. G. Edel’man and B. 1. Stepanov, Zhur. obshchei Khim.,1969,39,712 [ J . Gen. Chem. (U.S.S.R.), 1969, 39, 6781.

206

Organophosphorus Chemistry

has been discussed in relation to the dipole moments and U.V. spectra of these rn01ecules.~~19F chemical shifts have been cited as evidence that in compounds of the type, XYZP=N*C6H4F-p(X, Y, Z include Me, Et, Bun, Ph, NEt,, OMe, OEt, OPrn, and OBun) the XYZP=N- group is an electron However, basicity measurements on compounds of the type, P - X C ~ H ~ E ~ , P = N . C ~ H ~ N (XO= , - H, ~ C1, Me, NMe,, OMe, or COOMe), indicate that the =P=N- grouping does not transmit conjugative effects between the two aromatic ring The U.V. spectra of these compounds have also been The i.r. spectra of several N-acyl phosphazenes, RCO-N=PCl, (R = CF3, CC13, Ph, C&4C1-p, C6H4N02-p) and N-perhalogenoalkylphosphazenes, RN=PCI, (R = CF3CC12,CCl,CCl,) and their 15N analogues, show 59 conclusively that the absorption of the =P=N- stretching mode occurs in the range 1289-1396 cm-l. The 31P n.m.r. spectra of these compounds, and other esters of the types (RO),P=N-P(: O)(OR),, and (RO)R,P=N-P( :O)(OR), (R = alkyl or aryl) have been reported 6o as an aid to structural identification in these systems. 4 Synthesis of Cyclic Phosphazenes Only one new method of preparing cyclophosphazenes has been reported,61 and this in little detail. Thus, phosphorus pentachloride and one of the silicon-nitrogen compounds, (Me,SiNH),,, or (Me,Si),NH, or a mixture of these, gives the homologous series of chlorocyclophosphazenes,(NPCI,),. It remains to be seen whether the method offers advantages over conventional ammonolysis procedures. The role of catalysts in the formation of chlorocyclophosphazenes continues to attract interest. In one case, the reaction of ammonium chloride with phosphorus pentachloride with, and without, the use of chlorobenzene as a solvent was investigated.g2 In the absence of solvent, anhydrous metal halides increase the total yield of cyclic and linear phosphazenes, e.g. total yield with no catalyst was 58%, with AlCI, 67%, and with FeCl, 76%. However, the proportion of cyclic to linear homologues 65

56

57

6o

61

62

H. Goetz, B. Klabuhn, and H. Juds, Annalen, 1970, 735, 88. G. Genkina, V. A. Gilyarov, and M. I. Kabachnik, Doklady Akad. Nauk S.S.S.R., 1969, 188 (Chem. Abs., 1970,72, 66050). T. G. Edel’man and B. I. Stepanov, Zhur. obshchei Khim., 1969,39, 713 [J .Gen. Chem. (U.S.S.R.), 1969, 39, 6791. B. I. Stepanov and T. G. Edel’man, Zhur. obshchei Khim., 1969,39, 1549 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 15181. V. A. Shokol, A. A. Kisilento, and G. I. Derkach, Zhur. obshchei Khim., 1969,39, 874 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 8391. V. V. Sheluchenko, I. M. Filatova, E. L. Zaitseva, and A. Ya. Yakubovich, Zhur. 1969, 39, 1781. obshchei Khim., 1969, 39, 194 [J. Cen. Chem. (U.S.S.R.), S. M. Zhirukhin, V. V. Kireev, V. G. Kolesnikov, V. P. Popilin, and G. S. Kolesnikov, Otkrytiya Izobret, Prorn. Obraztsy. Tovarnye Znaki, 1969,46,24 (Chem. Abs., 1970,72, 123,535). S. M. Zhivukhin, V. V. Kireev, G. S . Kolesnikov, V. P. Popilin, and E. A. Filippov, Russ. J. Inorg. Chem., 1969, 14, 548.

Phosp hazenes

207

was, in general, slightly decreased by the presence of these metal halides. Yields of cyclic material were improved by the presence of metal halides in chlorobenzene solution, but relatively large quantities of halides resulted in a marked increase in the proportion of linear phosphazenes. To account for the latter observation, it was suggested that the terminal -PC12=NH groups, which are thought to act as nucleophiles in intramolecular cyclisation, were complexed by the metal halides. A second report 63 shows that the yield of N,P,C16 may be improved by about one-sixth if catalytic quantities of zinc chloride are used in the phosphorus pentachlorideammonium chloride reaction in chlorobenzene solution. With larger quantities of zinc chloride, a mixture of complex halide salts may be obtained. 6 4 PCl,

+ NH4Cl+ ZnC1,

150 "c

Ce&Ch

Cl(Cl,P=N),PCI,+ZnCl,-

(n = 1-10)

The products are liquids, thermally stable to 600 "C,and their possible use as high temperature lubricants has been considered. The reactions of dialkylaminophosphoranes with ammonia (or ammonium chloride) has already been considered (Section 2) ; only the dimethylaminoderivative, Me,NPCl,, has led to a cyclophosphazene: 3NH4C1

+ 3Me,NPCl,

--

N,P,CI,(NMe,),

+ 12HCl

The non-geminal trisdimethylamino-derivative was obtained as a mixture of cis- and trans-isomers, which were identified by lH n.m.r. spectroscopy. No evidence for higher homologues was reported, although eight-membered ring compounds are readily isolated from reaction with the analogous phenyl derivative, PhPC14. An interesting route to a new cyclophosphazene (28), which is related to the reaction of phosphorus pentachloride with chlorinated acetonitrile (Section 2), has been established:'j5 Na+N(CN),-+ PCl,

63

g5

[N=C=N- C(Cl)=N.kI,]

-

(28)

N. I,. Paddock and H. T. Searle, U.S.P., 3,462,247, 1969 (Chem. Abs., 1969, 71, 82,031). G . M. Nichols, U.S.P., 3,449,091 1969 (Chem. A h . , 1969, 71,31,905). M.Becke-Goehring and D. Jung, 2. anorg. Chem., 1970, 372, 233. I

64

-

208

Organophosphorus Chemistry

With dicyanamide, the analogous P-trichlorophosphazenyl derivative (29) is obtained: NC-N=C(NH,),

+ 2PC1,

cirf:4>

(29)

+ 4HCI

Under milder conditions ( G 6 5 "C) only khree moles of hydrogen chloride are lost, leaving the P-substituent, NHPC1,Cl-, in (29). As might be anticipated, the trichlorophosphazenyl group in (29) undergoes solvolysis with formic acid, leaving the ring intact: -N=PC13

+ HCO,H

-NHP(:O)CI,

+ HCI+CO

Cyanamide does not, however, give a cyclic product under similar conditions : H,NCN

+ 3PC&

[Cl,P=N- c(cI)=N-PCI,]+[PcI,]-

3. 2HC1

A route 66 to unsymmetrical cyclophosphazatrienes has also been described : RC(NHZ)=N.CI

+ R'ZPNCO

(32)

> [RC(NH,)= NPR1,NCO] +C1-

(31)

<

PC15

(30)

R = Ph; R1 = Ph or OPh R = C,H,Me-p; R1 = Ph or OPh

1

The salt [H2N(Ph2P=N),H2]+Cl- has been identified 67 as the main product of the reaction of chlorodiphenylphosphine and hydrazine hydrochloride in refluxing s-C2HzC14,although its mechanism of formation is unknown. Pyrolysis of this salt gives the hexaphenyl derivative, N3P3Ph6, probably by intramolecular condensation with loss of ammonium chloride. The eight-membered ring compound (33) has been obtained** by the reaction : Me2S(=N.PPh,),

67 G8

+ ClPPh, + Me,S(NBr,),

-

(33)

M. V. Kolotilo, A. G. Matyusha, and G. I. Derkach, Zhur. obshchei Khim., 1969, 39, 188 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 1731. E. F. Moran and D. P. Reider, Inorg. Chem., 1969, 8, 1550. R. Appel and W. Eichenhofer, Z . Nuturforsch., 1969, 24b, 1659.

209

Phosphazenes ,N=P-N Ph 2 \\

SMe

5 Chemical Properties of Cyclic Phosphazenes A. Addition Compounds.-Crystalline complexes are formed 69 by the addition of antimony pentafluoride to fluorocyclophosphazenes at 25 "C. Irrespective of the molar ratios of reactants, they have the stoicheiometry (NPF2),,2SbF5 (n = 3-6). In view of the known affinity of SbF, for fluoride ions, the volatility of the adducts (sublime < 100 "C in vacuo), and their spectroscopic properties, the authors were led to suggest that the adducts had non-ionic fluorine-bridged structures. The i.r. spectra indicate that the P-N bonds are strengthened, consistent with co-ordination of fluorine to two SbF5 molecules, or, more likely, a bridged Sb,F,, entity. Arsenic pentafluoride only forms a 1 : 1 complex with N5P6F10,which readily dissociates, and phosphorus pentafluoride and boron trifluoride form no adducts at 25 "C with the fluorocyclophosphazenes. Aluminium tribromide also forms 70 adducts with bromo- and chlorocyclophosphazenes in carbon disulphide solution, which are formulated, N,P,Br,,AlBr,, N,P3Br,,2AlBr,, and N,P,Cl,,AlBr,. Their general properties and i.r. spectra indicate that adduct formation arises from donation of a lone pair of electrons from a ring nitrogen atom to AlBr,, rather than by halogen transfer to form ionic species, e.g. N,P,Br,+AlBr,-. N3P3F6can also act as a Lewis acid. With caesium fluoride at ambient temperatures it gives 71 a hydroscopic adduct CsN3P3F7. Conductivity measurements show that it can act as a 1 : 1 electrolyte, but the possible anion structures (34) and (35) were not readily distinguished. F,

(34)

(3 5 )

B. Amino-derivatives.-An investigation of the reactions of the nongeminal bisdimethylamino-derivatives,N,P,Cl,(NMe,),, with KS02F and with SbF, has revealed 7 2 the two different fluorination mechanisms shown in Scheme 1. The fluorination of chlorocyclophosphazenes generally 6g

io i1

i2

T. Chivers and N. L. Paddock, J. Chem. SOC. ( A ) , 1969, 1687. G. E. Coxon and D. B. Sowerby, J. Chem. SOC.( A ) , 1969, 3012. W. M. Douglas, M. Cooke, M. Lustig, and J. K. Ruff, Inorg. Nuclear Chem. Letters, 1970, 6, 409. B. Green and D. B. Sowerby, J. Chem. SOC.( A ) , 1970, 987.

210

Organophosphorus Chemistry

proceeds by a pairwise (geminal) replacement pattern as is observed for KS0,F. A tentative suggestion to account for the unexpected route observed for SbF3 is that this reagent initially complexes with the ring nitrogen atom between the two =PCl(NMe,) groups (expected to be the most basic) and so is in a position to fluorinate initially at these groups. Co-ordination to the ring nitrogen atom should also make the adjacent phosphorus atoms more electrophilic, so that loss of SbF3 would account for the fact that subsequent fluorination at the =PCl, group is much slower. The tetrafluorides N3P3F4(NMe2),may be obtained by reaction of the chloride-fluorides with KS02F, or with NaF. The reactions 73 of the geminal diphenyl derivative, N3P3C14Ph,,with ammonia, dimethylamine, and aniline to give derivatives of the type, N3P3Ph2Cl4_,(NRR1),(R = R1= H, n = 2 or 4; R = R1 = Me, n = 1, 2, or 4; R = H, R1 = Ph, n = 1, 2, or 4), have been followed in detail. Both ammonia and aniline replace chlorine atoms by a geminal route (n = 2), but with dimethylamine a non-geminal route is followed (n = 1 or 2). This behaviour closely parallels that observed for reactions of these amines with the hexachloro-derivative, N3P3C1,. Structures were established by the preparation of mixed aminodimethylamino- and anilinodimethylamino-derivatives, by basicity measurements, and by IH n.m.r. spectroscopy. Two geminal amino-derivatives, N3P3Ph4(NRR1), (R = R1= Me; R = H, R1 = Ph) were also prepared. Bis- and hexa-(pheny1hydrazino)-derivatives of N3P3C1, have been isolated 74 and the structure of the bis-derivative, N3P3C14(NHNHPh),, identified as trans-non-geminal. This structure was established by the preparation and examination of the IH n.m.r. spectra of isomeric mixed amino-derivatives, N3P3(NMe,),(NHNHPh),. If this aminolysis route is general, then phenylhydrazine is one of the few primary amines to replace the chlorine atoms in N3P,Cl, by a predominantly non-geminal route. 73 74

V. B. Desai, R. A. Shaw, and B. C. Smith, J. Chern. SOC.( A ) , 1969, 1977. M. R. Pitina, V. V. Negrebetskii, and N . I. Shvetsov-Shilovskii, Zhur. obshchei Khirn., 1969, 39, 1216 [J. Gen. Chem. (U.S.S.R.), 1969, 39, 11861.

Phosphazenes

21 1

Further investigation75 of the products of reaction of N,P,CI, and isopropylamine 76 shows that adducts may be formed from compounds of different degrees of aminolysis, or even from isomeric compounds. Attempts to prepare tris- and tetrakis-(isopropy1amino)-derivatives gave the adducts, N3P3Cla(NHPri)2,N3P,C12(NHPri), and 2,2:4,4,6,6-N3P,Cl2(NHPr'),,2,4:2,4,6,6-N~P~Cl~(NHPri)~ respectively, both with sharp melting points, although the components could be separated by chromatography. Basicity measurements also indicated that a mixture of compounds was present in each case. Ph

R

I

I

i.

.=NMe2 .I=

NMe2

R=Me

R

= Ph

R1= Me, or R12 = (CH2)2

R1 = H, Me, or R12 = (CH2)2, (CH,),, (CHz)2WH2)2

R = H, Me, Et, and NR, = imidazolyl (37)

(36)

Interest in the properties of the cyclodiphosphazatrienes reported last year continues. A number of fully aminolysed derivatives (36) and (37) have been obtained7, from the analogous chlorides. IH and 31Pn.m.r. showed that the ratio of cis- to trans-isomers in compounds of structure (37) was the same as that in the chlorides from which they were derived, indicating that aminolysis occurred with complete retention or inversion of configuration at phosphorus. The same behaviour is observed for partially phenylated derivatives of N,P,C1,. When R = H (38), pyrolysis results in loss of ammonia, and then benzonitrile to give an insoluble polymer:

(38)

(39)

(40)

A novel bicyclic phosphazene ring system (41) has been synthesised 7 7 by reaction of the geminal bis(trichlorophosphazeny1) derivative, 76

77

S. K. Das, D. Feakins, W. A. Last, S. N. Nabi, S. K. Ray, R. A. Shaw, and B. C. Smith, J . Chem. SOC.( A ) , 1970, 616. A. Schmidpeter and N. Schindler, 2. anorg. Chem., 1969, 367, 130. W. Lehr, 2. anorg. Chem., 1969, 371, 225.

212 N,P,Cl,(N=PCI,),,

Organophosphorus Chemistry with heptamethyldisilazane:

N,P3CI,(N=PCI3),

+ (Me,Si),NMe

-

(41)

+ 2Me3SiC1

C1, P-N

N=PCI, \NMe \ /\ / CI,P=N N’PCI,

More examples of dimethylamino-derivatives of N*P4C16 have been reported76 and the structures assigned are those shown in Scheme 2.

0

6 n = 2

n= 3

n = 4

n = 5

n=6

Structures of N4P4Cl,-,(NMe,), derivatives. The corners of the structures shown represent the positions occupied by phosphorus atoms. A full line represents an NMe, group above the plane of the ring and a dotted line an NMe, group below the plane of the ring Scheme 2

Dimethylamine replaces chlorine by a mixture of geminal and non-geminal routes. The former route is more important than in the case of reactions with N,P,Cl,. Mixtures of the above tris- and tetrakis-dimethylaminoderivatives have been fluorinated 7 9 with excess of antimony trifluoride. Fluorination proceeded more smoothly than with the trimeric dimethylamino-derivatives, N,P,Cl,(NMe,),, to give isomeric mixtures of N4P4F6(NMe2)3 and N4P4F4(NMe2)4 (separated by g.l.c.), probably with non-geminal structures. The former compound gave isomers of N4P4C13F5 with hydrogen chloride. The substitution *O of vanadium for phosphorus has been achieved in the tetrakis(trichlorophosphazeny1) derivative (42) by reaction with vanadyl chloride : (42) 78 78

+ VOCl,

---+

(43)

V. B. Desai, R. A. Shaw, B. C. Smith, and D. Taylor, Chem. and Znd., 1969, 1177. B. Green and D. B. Sowerby, Inorg. Nuclear Chem. Letters, 1969, 5 , 989. A. Slawisch and J. Pietschmann, Z . Naturforsch., 1970, 25b, 321.

21 3

Phosphazenes

(43)

(42)

The positions of the substituents were established by 3lP n.m.r. spectroscopy and the structure of the starting material, since it was derived from a tetrakis(amin0)-derivative, shows that ammonia replaces 81 chlorine in N4P4CIS by a geminal route, as observed for N3P3C1,. C. Aryl Derivatives.-It is known that N3P3F6and phenyl-lithium undergo smooth reactions to give phenylated cyclophosphazenes in which fluorine atoms are replaced in a non-geminal manner. However, phenylation 82 of N3P3F6by phenyl magnesium bromide has now been shown to proceed geminally (at least as far as the bis-derivative, N3P3F4Ph2).This further illustrates a point well established for chlorophosphazenes, namely that the nature of the products of reaction with an organometallic reagent is very sensitive to the nature of that reagent. Phenyl magnesium bromide and N4P,CI, have now been showns3 to the octaphenyl derivative, give four products, two isomers of N4P4Ph4C14, N4P4Ph8,and biphenyl, the proportions of which depend on the solvent used. One of the tetraphenyl isomers is generally obtained in good yield (>80%) and is found to contain a trimeric, rather than a tetrameric, ring system, formulated as N3P3C14Ph(N=PPh,) (reported last year). In the other isomer the tetrameric ring system is retained and the phenyl groups are bonded to two phosphorus atoms [shown by degradation to Ph2P(:O)OH], but decisive evidence with which to distinguish the isomers (44) and (45) was not obtained. As in the phenylation of N3P3C&,these

-.

(44)

(45)

reactions are visualised as proceeding uia co-ordination of a ring nitrogen atom to PhMgBr, allowing cleavage of an adjacent P-N bond to accompany phenylation. Further phenylation of the resultant linear intermediate, 82

8s

W. Lehr and J. Pietschmann, unpublished results cited in ref. 80. C. W. Allen, Chem. Comm., 1970, 152. M. Biddlestone and R. A. Shaw,J . Chern. SOC.(A), 1970, 1750.

8

Organophosphorus Chemistry

214

followed by recyclisation, could give the two tetraphenyl derivatives. The use of diphenylmagnesium for phenylation of N,P,Cl, also results in the same four products, but with a larger proportion of N3P3C14Ph(N=PPh3) (93%). D. Aryloxy- and Alkoxy-derivatives.-Unusual reactions 84 occur between cyclophosphazenes and ortho-aminophenol in refluxing benzene solution. For example, N3P3C16is degraded to a phosphorane (46) and is not converted to a substituted cyclophosphazene:

The nature of the five-co-ordinated phosphorus compound (46) was established by a number of spectroscopic methods and it is also obtained

from similar reactions with (NPXz), (X

(n-15,000),

and

=

F or Br), N4P4C18,(NPC12)n

(X = 0, S, or NH). However,

N 3 P 3 $ 0 ) 3

cyclophosphazenes with independent substituents, e.g. N3P3R6(R = OPh, OC6H4N02-p, NHPh, and OCH2CF3), were unaffected under similar conditions. This unusually rapid degradation of the phosphazene ring or polymer is most likely to be associated with the strain inherent in the five/\

membered rings common to these systems. For example, the 0-P-0 angle in is known to be 97", whereas the exocyclic angle at 3

phosphorus in phosphazenes is generally 103-104". This ring strain would therefore be diminished in a structure with five- or six-co-ordination at phosphorus-hence the driving force to obtain (46). The kinetics of the basic hydrolysis of hexakis(ary1oxy)cyclotriphosphazatrienes, N3P3(0R)6(R = Ph, C6H4No2-p,C6H,N02-o, and 84

H. R. Allcock and R. L. Kugel, J . Amer .Chem. SOC.,1969,91, 5452.

21 5

Phosphazenes

C,H,Me-p), have been followed 86 by U.V. spectroscopy. The cleavage of one side-group was shown to be first order in phosphazene and first order in base : =P(OR),

+ 2NaOH

-

=P(OR)(ONa)

+ NaOR + H,O

An SN2-type mechanism was suggested to be operative, and the ease of cleavage of the aryloxy-groups parallels an increase in acidity of the appropriate phenol, i.e. rate for C,H,Me-p < Ph < CGHdNOz-O< C~HdN02-p

-

Kinetic studies have also been carried out on the reactions of alkoxyphosphazenes with silyl halides : N3P3(OR)6

+ nCISiR1,

+

N3P3(OR),-,(OSiR1,), RCl (R = alkyl, R1 = Me or Ph)

By measurement of the rate of RC1 elimination, the reaction was found to be first order in the chlorosilane and zero order in the phosphazene. It was suggested that the slow step is formation of a siliconium ion, e.g. R13Si+,which then reacts with the oxygen atom:

Evidence cited in favour of siliconium ion formation included the fact that the rate of reaction increases with increasing number of halogen substituents on silicon and addition of Lewis acids (e.g. FeCl,). The ability of certain aryloxy- and amino-derivatives of N3P3C16to form addition compounds with organic molecules is well known. This ability in

has been utilised in an interesting patent which describes how the vapours of Cs and C, alkyl- and alkenyl-benzenes may be separated, presumably by clathrate formation. Several alkoxy- and aryloxy-derivatives of cyclodiphosphazatrienes [(47) and (48)] have been obtaineds8 by reaction of the appropriate chlorides with alcohol (R0H)-pyridine mixtures, or with ,sodium alkoxides, RONa, 86

86

87 88

H. R. Allcock and E. J. Walsh, Chem. Comm., 1970, 580. S. I. Belykh, S. M. Zhivukhin, V. V. Kireev, and G . S. Kolesnikov, Zhur. obshchei Khim.,1969, 39, 799 [J.Gen. Chem. (U.S.S.R.), 1969, 39, 7611. British Petroleum Co., Fr. P. 1,525,419 (Chem. A h . , 1969, 71, 38,561). A. Schmidpeter and N. Schindler, 2. anorg. Chem., 1970, 372, 214.

Organophosphorus Chemistry

216 R( I

=

Me, Ph, NMe,)

where R includes Me, Et, Prn, Bun, and C,H,Me-p. During attempts to prepare alkoxy-derivatives (48) (R = Me), it was found that n-butanol and pyridine give the ring degradation products ( B u ~ O ) ~ P = N P( :O)(OBun), and [H,N=C(Me)NH,]+Cl-, a reaction which was probably initiated by protonation of a ring nitrogen atom. The formation of a compound of structure (48) was generally accompanied by the corresponding chlorotri(a1koxy)-derivative. In most cases the tri- and tetra-(a1koxy)-derivatives were not separated, but identified by lH and 31P n.m.r. spectroscopy.

E. Mercapto-derivatives.-The

hexafluoride N3P3F6with sodium ethylmercaptide in ether (or dioxan) gives 89 a series of ethylmercaptocyclophosphazenes :

+

N3P3F6 nNaSEt

-

N3P3F6-,(SEt),

+ nNaF

(n = 1-5)

lH, 19F,and 31Pn.m.r. spectroscopy showed that, when n = 2-4, geminal structures were obtained, as in the reactions of N3P3CI, with sodium eth ylmercapt ide.

6 Polymeric Phosphazenes The chemistry of polymeric phosphazenes ti and of phosphorus-nitrogen polymers has been reviewed. The synthesis B1 of polychlorophosphazenes, (NPCl,),, end-stoppered by the elements of PCl, and of HCl, has been studied in detail. Thermal polymerisation of N3P3Cl, in the presence of hydrogen chloride gave polymers of lower molecular weight than in its absence. These polymers and sodium alkoxides (aryloxides) gave hydrolytically stable polymers, [N=P(OR),],, whose intrinsic viscosities were measured. Thermal analysis shows that the aryloxy-derivatives have better stability than the alkoxyderivatives. In the cases where R = CH2CF3, C,H,Me-p, and C6H4Cl-p, polymer fractionation was carried out O2 and the mechanical and dielectric properties of the polymers assessed. The i.r. spectrum of thermally prepared (NPCl,), in the region 500&

91 g2

E. Niecke, 0. Glemser, and H. W. Roesky, 2. Nafurforsch., 1969,24b, 1187. E. Kobayashi, Kagaku To Kogyo (Tokyo), 1969,22,344(Chern. Abs., 1970,72,91,036). G.Allen, C. J. Lewis, and S. M. Todd, Polymer, 1970,11, 31. G. Allen, C. J. Lewis, and S. M. Todd, Polymer, 1970,11, 44.

Phosphazenes 217 20 cm-1 suggests D3 that the polymer chain has a distorted ‘cis-plan’ helical structure of C2symmetry, where the chlorine atoms on alternate phosphorus atoms are aligned with one another. The polymer (NPC12), has also been usedD4as the precursor of new petrol-resistant elastomers, [NPR2-NPR1,], (R = OCH2CF3, R1 = OCH2C,F,n) which have good stability over the range, - 6 5 to 600 O F . Diethylamine replaces the chlorine atoms in (NPC12), in a non-geminal manner to giveD5INPCl(NEt2)],, and the remaining chlorine atoms have been replaced by NH2, NHMe, NHEt, NHPrn, NHBun, NCSHI0, and OCH2CF3groups. These polymers are generally flexible, transparent, and hydrolytically stable, with molecular weights in excess of 2 x 105. New polymers, [P=NR(Cl)NH], (R = Me or Ph), have been obtained Q6 by reaction of the ‘monophosphazenes’, (MeN=PCl,), and PhN=PC13, with ammonium chloride in various solvents, or by heating the neat reaction mixture to 170 “C. These polymers were unaffected by triethylamine or by pyridine, but water and ammonia (with pyridine) gave [P(NR)(OH)NH], and [P(NR)(NH,)NH],, respectively. The latter gave polymers, [P(:NR):N],, on heating at 250 “C. Other phosphazene polymers have been obtained from the reaction of alkoxyphosphazenes with chloro~ilanes,~~ or with halogeno-hetero-organic Bisphenols and N3P3C16provide e l a ~ t o m e r s ,while ~ ~ the properties of copolymers derived from various olefins are reputed looto be improved by treatment with N3P3Cl, or N4P4Cl,.

7 Miscellaneous Physical Measurements The i.r. and Raman spectra of geminally substituted fluoride-chlorides N3P3C16-,F, (n = 0-6) have been reported lol and discussed. Photoelectron spectroscopy has been used lo2to determine the ionisation potentials of the fluorides (NPF2), (n = 3-43), and electron impact measurements gave the same parameters for (NPX2), (X = C1, n = 3-7; X = OCH2CF3, OMe, OPh, NMe, or Me, n = 3 or 4). For a given substituent, the first ionisation potential is generally greater when n = 3, than when n = 4, and in the fluoride series the ionisation potentials alterT. R. Manley and D. A. Williams, Polymer, 1969, 10,307. S. H. Rose and J. Cable, U.S. Clearinghouse Fed. Sci. Tech. ZnJ, AD1969, AD693289 (Chem. A h . , 1970, 72, 91288). 95 H. R. Allcock and D. P. Mack, Chem. Comm., 1970, 685. 06 S. M. Zhivukhin, V. V. Kireev, S. S. Titov, and G. S. Kolesnikov, Vysokomol.Soedinenii, 1969, 11, A , 1610 (Chem. Abs., 1969, 71, 102,403). 9 7 S. M. Zhivukhin, V. V. Kireev, G. S. Kolesnikov, and S. S . Titov, Vysokornol.Soedinenii, 1969, 11, B, 837 (Chem. Abs., 1970, 72, 55,959). 98 S. M. Zhivukhin, V. V. Kireev, G. S. Kolesnikov, and I. M. Raigorodskii, Otkrytiya Izobret. Prom. Obraztsy. Tovarnye Znaki, 1969,46,90 (Chem. Abs., 1970,72,133,638). 9Q Nord-Aviation, Gen. Offen., 1,932,503 (Chem. Abs., 1970, 72, 67,682). l o o A. F. Halasa and R. W. Koch, Fr. Demande, 2,003,679 (Chem. Abs., 1970,72,101,626). lol J. Emsley, J. Chem. SOC.( A ) , 1970, 109. Io2 G. R. Branton, C. E. Brion, D. C. Frost, K. A. R. Mitchell, and N. L. Paddock, J. Chern. SOC.(A), 1970, 151. 94

21 8

Organophosphorus Chemistry

nate with ring size. The results have been discussed in terms of n-bonding within the phosphazene ring systems. The electronic structure of N,P3C1, has been briefly discussed lo3elsewhere. The enhancement of 31P n.m.r. signals by the presence of certain free radicals (dynamic nuclear polarisation) has been observed for a number of cyclophosphazenes. In one case,lo4 the series (NPC12), (n = 3-7) was examined in the presence of four different free-radical sources. For each radical, a definite order of enhancement was observed, which may be related to the changes in chemical properties of the phosphazenes. In the second study,lo5the effects of a wide range of substituents in the phosphazene ring on the magnitude of enhancements were noted. A theory was proposed to account qualitatively for the observed effects. The appearance of the lH n.m.r. spectra of symmetrical cyclotriphosphazatrienes, N3P3C13(OMe)3,N,P,Cl,(NMe,),, and N3P,Ph2(NMe,),, has been compared lo6with that calculated for [AX,], (A = ,lP, X = lH) spin systems, but the band shapes have not yet been properly matched. The lack of fine structure in the observed spectra is a particular problem and the possible reasons for the absence of this have been discussed. Polarographic reduction lo’ of (NPPh)3,4 and of several cyclophosphazenes with aryloxy-substituents in the cavity of an e.s.r. spectrometer results in the formation of phosphazene radical anions. The e.s.r. signals from these radical species indicate that in the case of the aryloxy-derivatives the unpaired electron is restrained within the locality of the aromatic ring, but that in the case of the phenyl derivatives the unpaired electron is delocalisedover the Ph-P-Ph unit, or even over thephosphazene ring skeleton. The recently measured basicities lo8 of cyclotriphosphazatrienes with chloro-, amino-, and phenyl groups have been utilised in conjunction with earlier data to calculate ‘substituent constants’ for amino-groups. These constants can be used to predict the basicity of any cyclophosphazene with a specific combination and orientation of substituents, enabling structural assignments to be made. Further studies logof the U.V. spectra of halogenocyclophosphazenes, N3P3X6(X = F, Cl, or Br), N4P4X8(X = F, Cl, or Br), and the mixed halides N,P,C15Br and N3P3C14Br2have been reported and interpreted in terms of a three-centre bonding scheme. The heat capacity and entropy of N3P3(NH2)6,H20 is 11.768 kcal mol-1 and 70.98 cal deg-l mol-1 (at 298 K) respectively.llO M. Pelavin, D. N. Hendrickson, J. M. Hollander, and W. L. Jolly, J. Phys. Chem., 1970,74, 11 16. lo4 R. A. Dwek, N. L. Paddock, J. A. Potenza, and E. H. Poindexter, J. Amer. Chem. SOC. 1969,91, 5436. lo6 R. A. Dwek, R. E. Richards, D. Taylor, and R. A. Shaw, J . Chem. SOC. (A), 1970,1173. lo8 E. G. Finer, R. K. Harris, M. R. Bond, R. Keat, and R. A. Shaw, J. Mol. Spectroscopy, 1970, 33, 72. lo’ H. R. Allcock and W. J. Birdsall, J . Amer. Chem. SOC.,1969, 91, 7541. lo* D. Feakins, R. A. Shaw, P. Watson, and S. N. Nabi, J. Chem. SOC. (A), 1969, 2468. loS B. Lakatos, A. Hesz, Z . Vetessy, and G. Horvath, Actu Chim. (Budapest), 1969,66,309. Z. T. Wakefield, B. B. Luff, and J. J. Kohler, J. Chem. and Eng. Data, 1970,15,246.

lo3

ll4

llS

ll1

\

Ph/P=N, F

Me

1.641 (0.002)

N-3P-4 1.539 (0*005) P-4N-5 1-555 (0.004)

(0’0°5)

P-F 1.488 (0.002) P-c 1-806 (0-003)

P-Ph 1.779 (0.009)

(0.005)

P-F 1.527

1.563 (0.007)

P-2N-3 1.617

118-5

P-c1 1.963 (0.005)

NPF 118.7 (0.1) NGC 110.8 (0.1)

A

NP-2N 115.5 (0.3) NP 4N : 120.5 (0.2)

A

(0.5)

~f;”

P-x

P-N

PGC 119.1 (0.2)

107.9 (0.3) A FPF 96.9 (0.2)

c:c

100-5 (0.2)

XGX

Average bond angles (O)*

R. Olthof, Acta Cryst., 1969, B25,2040. C. W. Allen, J. B. Faught, T. Moeller, and I. C. Paul, Znorg. Chem., 1969, 8, 1719. J. Trotter and S. H. Whitlow, J. Chem. SOC.( A ) , 1970, 455. J. Trotter and S. H. Whitlow, J. Chem. Soc. (A), 1970, 460.

Compound

Average bond distances (A)*

X-Ray. Monomeric P-N length indicates strong multiple bonding. PNC unit non-linear

X-Ray. Five ring atoms coplanar, but Pz 0.20 8, out of plane. P-N bond lengths alternate as expected

1

113 114

112

111

Reference

X-Ray. P-F not located due to disordered structure. Ring planar and P-N bonds equal within expl. error

Comments

8 Molecular Structures of Phosphazenes and Related Compounds determined by Diffraction Methods %

8

!i

Q

x

2

3?

Me

11*

116 11'

115

2'07-2.15 (0.02)

1.591 (0.010)

1.88 (0.06)

P-c 1-806 (0.017)

1 606 (0.035)

P-F 1.570 1.605

P-c 1.820 (0.042)

1-595 1.735

Average bond distances (A)*

70.7

A

88.4-95.5

-

PNP 132.3 (3.8)

X-Ray. Ring planar. Plane of ring includes 2C1, both Me, and CCI. P-N very long

X-Ray. Fe has tetrahedral configuration. Rings nonplanar

X-Ray. N i has tetrahedral configuration. Rings nonplanar

C?C 105.9 (1.0)

PNP 127.3 (1.5)

A

Electron diffraction. Preliminary data. Ring planar and Me groups in this plane. Arrangement at each P atom is a distorted trigonal bipyramid

118

117

116

115

Reference

88.5 103.9

Comments

77.9

Average bond angles (O)*

A. Almenningen, B. Anderson, and E. E. Astrup, Acta Chem. Scand., 1969, 23, 2179. M. R. Churchill, J. Cooke, J. Wormald, A. Davison, and E. S. Switkes, J. Amer. Chem. Sac., 1969, 91, 6518. M. R. Churchill and J. Wormald, Chem. Comm., 1970, 703. M. L. Ziegler and J. Weiss, Angew. Chem. Internat. Edn., 1969, 8, 455.

* Standard deviations in parentheses.

Compound

E

Br;

2

5

0

5

10 Photochemistry, Radicals, and Deoxygenation Reactions BY R. S. DAVIDSON

1 Photochemistry y-Irradiation of triphenylphosphine adsorbed on silica has been shown by U.V. absorption spectroscopy to produce the triphenylphosphinium radical cati0n.l The silica acts as an efficient electron acceptor. Triphenylphosphine and trimethyl phosphite have been found to quench the reactions of triplet benzophenone.2 The quenching action was ascribed to exciplex formation, i.e. formation of an excited complex between the ground state phosphine and the excited carbonyl compound in which some electron transfer from phosphine to the carbonyl group has occurred. Irradiation of benzophenone in the presence of triphenylphosphine has been shown to lead to deoxygenation of the carbonyl group with the formation of diphenylmethylene (l).3 The latter reacts with the phosphine to give an PhtCO* + Ph3P

- [PhzCO - - P P h ] *

Ph,CO + Ph,P

+

k e n c h i n g

Exciplex

Ph,C :PPh,

Electron Transfer'

-

Ph,C-6

FPh,

I Ph,C : + Ph,PO (1)

ylide. Triphenylphosphine has also been found to quench the fluorescence of biacetyl, fluorenone, and anthracene and again exciplex formation was invoked to explain the deactivation.2 The photoinduced cleavage of P-H bonds, as a means of forming phosphino-radicals, has been utilised in studies of the addition of these radicals to olefins. Dimethyl- and hexafluorodimethyl-phosphino-radicals have been found to react with olefins to give, in general, high yields of ph~sphines.~" The formation of cis-but-Zene in the reaction with transbut-2-ene (2) indicates that the addition of the radicals is reversible. a 4

P. K. Wong and A. 0. Allen, J. Phys. Chem., 1970,74, 774. R. S. Davidson and P. F. Lambeth, Chem. Comm., 1969, 1098. L. D. Wescott, H. Sellers, and P. Poh, Chem. Comm., 1970, 586. R. Fields, R. N. Haszeldine, and J. Kirman, J . Chem. SOC.( C ) , 1970, 197; R. Fields, R. N. Haszeldine, and N. F. Wood, ibid., 1970, 744; R. Fields, R. N. Haszeldine, and N. F. Wood, ibid., 1970, 1370.

Organophosphorus Chemistry

222

Me,P" + MeCH=CHMe

-

y e MeCHPMe,CHMe

Addition to fluorinated alkenes has been used to probe the electrophilic character of phosphino-radicals, e.g. (CF,),$ should be more electrophilic than Reactions with 1,1,2-trifluoroethylene 4b and 1,1difluoroethylene 4c showed that electrophilic character decreased from (CF3)2+ to fiH2 to Me,$. Electron spin resonance studies have shown that y-irradiation of trifluorophosphine in an argon matrix gives difluorophosphino- and tetrafluorophosphoranyl radicals.6 The difluorophosphino-radicals still have a tumbling motion at 77 K but are frozen out at 4.2 K. Full details of the e.s.r. spectra of the dichlorophosphino- and tetrachlorophosphoranyl radicals produced by u.v.-irradiation of phosphorus trichloride have now been published.6 The u.v.-initiated reaction of thiophosphoryl chloride with cycloalkanes to give cycloalkyl phosphonothionic dichlorides has been reported to occur in high yield.' Other reported photoinitiated radical reactions include the addition of 00-diethyl phosphonothionic acid to unsaturated sugars 8 a and of dialkyl phosphites to polyfluorocyclobutenes.8b In the latter reaction unsaturated phosphonates [e.g. (3)] were formed.

(3)

y-Irradiation of triethyl phosphite has been shown to give products derived by homolysis of C-H, P-0, and C-0 bonds.Q The yield of products derived by P-0 bond fission, i.e. triethyl phosphate and ethyl diethylphosphonate, was surprisingly low when compared with that from the u.v.induced reaction.1° Some interesting studies on the photoreactions of ylides have been reported.ll Irradiation of cyclohexene solutions of the ester phosphorane (4) gave benzene, whereas the diphenylmethylene(EtO),P

lo

l1

3

EtOH + (EtO),POH + (EtO)3P:0 + (EtO),P(: 0)OEt

W. Nelson, G. Jackel, and W. Gordy, J. Chem. Phys., 1970,52,4572. G . F. Kokoszka and F. E. Brinckman, J. Amer. Chem. SOC.,1970,92,1199. U. Schmidt and A. Ecker, Angew. Chem. Internat. Edn., 1970, 9, 458. a K. Kumamoto, H. Yoshida, T. Ogata, and S. Inokawa, Buli. Chem. SOC.Japan, 1969, 42, 3245; bT.Ueda, K. Inukai, and H. Muramatsu, ibid., 1969, 42, 1684. K. Terauchi, Y. Aoki, and H. Sakurai, Tetrahedron Letters, 1969, 5073. K. Terauchi and H. Sakurai, Kogyo Kagaku Zusshi, 1969,72, 215 (Chem. Abs., 1969, 70, 86,820~). Y Nagao K . Shima, and H. Sakurai, J. Pharm. SOC.Japan, 1969,72,236 (Chem. Abs. 1969,70, 114,372); Y . Nagao, K. Shima, and H. Sakurai, Kogyo KagakuZasshi, 1969, 72, 236 (Chem. Abs., 1969, 71, 61,493); Y. Nagao, K. Shima, and H. Sakurai, Tetrahedron Letters, 1970, 2221.

Photochemistry, Radicals, and Deoxygenation Reactions

223

phosphorane ( 5 ) gave benzene only when irradiated with light of wavelength 253-257nm. Use of higher wavelengths (e.g., 320-400 and 400-500nm) led to the formation of products derived from diphenylmethylene (e.g., tetraphenylethane). The phosphole (6) has been shown Ph,P:CHCO,Me (4)

P h o P h Ph

Ph

to photodimerise12 and the ease of this reaction casts some doubt upon the assignment of aromatic stabilisation to the phosphole system. The reported synthesis of the phosphepine (8) has, as its first step, the (2+2)cycloaddition of (7) to dich10romaleirnide.l~ Triplet sensitisation of the 0

Q

Ph‘

%O

+

c~+jH c1 0

A

H

+

anti-isomer

c1

(7) I

phosphine oxide (9) has been shown to give (11) via the cyclobutene (lO).l* Direct irradiation of the phosphine (12) (A> 300 nm) yields (13) by a di-7r-methane rearrangement. The first excited singlet state appears to be responsible for this reaction. Dialkyl-a-ketophosphonates(14) undergo an intriguing photoinduced rearrangement to give phosphonates (15).16 A Norrish Type I1 reaction does not occur. The formation of .phenylphosphonates is indicative of the Type I reaction being competitive. The type of la

lS l4

l5

T. J. Barton and A. J. Nelson, Tetrahedron Letters, 1969, 5037. G. Mark1 and H. Schubert, Tetrahedron Letters, 1970, 1273. T. J. Katz, J. C. Carnahan, G. M. Clarke, and N. Acton, J . Amer. Chem. SOC.,1970, 92, 734. Y. Ogata and H. Tomioka, J . Org. Chem., 1970,35, 596.

Organophosphorus Chemistry 0

224 O*p/

Ph hv Corex Acetone

(9)

fPh

0

0

0

II

II

II

hv

RCO*P(OCHR2)2BenzeneT RCO*CR2.POCHR2 4- PhP(OCHR2)z I (14) OH (15)

,R ? 0 II PhCO -P (0R ) 2

___, It V

,R2

O/c'O I

I ,C-R1 / o \ R2 R2 (16)

R' -C,

R' = P h R2 = -P(OR)2

II

0

products formed by irradiation of dialkyl benzoylphosphonates has been shown to depend upon the nature of the alkyl groups.lS When hydrogen abstraction from the alkyl group is not efficient, trioxan formation (16) occurs, and when it is efficient pinacols are produced. The pinacolisation appears to occur from the triplet state of the ketophosphonate since the reaction is quenched by the piperylene. An examination has been made of the e.s.r. spectra of the radicals produced by irradiation of dialkyl benzoylphosphonates at low temperatures ( 156 K).17 All the radicals showed a N

l8

l7

K. Terauchi and H. Sakurai, Bull. Chem. SOC.Japan, 1970, 43, 883. K. Terauchi and H. Sakurai, Bull. Chem. SOC.Japan, 1969,42,2714.

Photochemistry, Radicals, and Deoxygenation Reactions

225

large doublet (splitting 53-1 28 G) which indicates that delocalisation of the odd electron extends to the phosphorus atom. 3,5-Dimethoxybenzyl phosphates have been shown to undergo photoinduced hydrolysis and benzyl carbonium ions appear to be intermediates.18 y-Radiolysis of cyclohexane solutions of red phosphorus containing methyl disulphide gives cyclohexyl-SS-dimethylphosphonodithioite.lgThe formation of this product was interpreted in terms of initial production of a cyclohexyl polyphosphine, (CBH11P4)n, which reacts with the disulphide to give the phosphorus ester. This latter reaction is reminiscent of the u.v.initiated reaction of pentaphenylcyclopentaphosphine with disulphides which was reported last year 2o and which gives phenyl-SS-dialkylphosphonodithioites. In this case, product formation uia phenylphosphinidene was suggested. Likewise, there is the possibility of cyclohexylphosphinidene participating in the radiolysis reaction. Irradiation and thermal decomposition of the phosphazine (17) leads to the formation of diphenylmethylene.21 Ph,P=N-N=CPh,

---+

Ph3P+ N, + Ph,C :

(17)

Ph,P=N'

+ 'N=CPh2

-

Ph,C=N*N=CPh2 (18)

Decomposition by homolysis of the N-N bond can occur and this results in azine (18) formation. Thermal decomposition (> 165 "C) of (17) in decalin was shown to give diphenylmethyl radicals which were identified by e.s.r. 2 Radical Reactions Reaction of optically active ph osphines with tet racyanoquinonedimethide in aqueous solution has been found to give racemic phosphine oxides.22 The reaction is claimed to occur via phosphonium radical cations. The observation of e.s.r. signals in the reaction of phosphites with 4-bromocyclohexa-2,5-dienonehas led to the suggestion that the phosphite radical cation and dienone radical anion are intermediate^.^^ Dynamic nuclear polarisation studies have shown that phosphines, phosphites, phosphine

2o

21 a2

23

V. M. Clark, J. B. Hobbs, and D. W. Hutchinson, Chem. Comm., 1970, 339. M. Scheffler and A. Henglein, 2. Naturforsch., 1970, 25b, 103. 'Organophosphorus Chemistry,' ed. S. Trippett, (Special Periodical Report), The Chemical Society, London, 1970, Vol. 1, p. 256. D. R. Dalton and S . A. Liebman, Tetrahedron, 1969, 25, 3321. R. L. Powell and C. D. Hall, J. Amer. Chem. Soc., 1969, 91, 5403. N. N. Kalibabchuk, G. V. Sandul, and V. D. Pokhodenko, Zhur. obshchei Khim., 1969, 39, 2140 (Chem. Abs., 1970, 72, 31,280g).

226

Organophosphorus Chemistry

and phosphazenes 24b interact with such radicals as the 2,4,6-trit-butylphenoxyl radical. The phosphabenzole (19) has been shown to react with 2,4,6-triphenylphenoxy- and diphenylamino-radicals to give pentacovalent derivatives [e.g., (20) and (21)].26 Electrolytic oxidation of these Ph

derivatives gives radical cations whose e.s.r. spectra indicate that the unpaired electron is mainly limited to the aromatic system. The reactions of phosphines and phosphites with alkoxy-radicals have been thoroughly investigated by means of e.s.r. spectroscopy.26Tri-isobutyl-, tri-isopropyl-, and tricyclohexyl-phosphines react with t-butoxyl radicals to give the corresponding alkyl radical.26a Reaction of this alkoxy-radical with Buts'

+ R,P

-

R,P=S

+ But'

trimethylphosphine was found to produce a radical whose e.s.r. spectrum is consistent with the assignment of the structure Me3$OBue.2eaThis is the first observation of a phosphoranyl radical. The aforementioned phosphines react with the t-butylthiyl radical to give a t-butyl radical.26a With triphenyl phosphite a displacement reaction occurs and a phenoxy-radical is t-Butoxy-radicals abstract hydrogen from trialkylphosphine oxides 26a and trialkyl phosphates.26b (Pri),P=O (MeO),P=O

(Pri),P(: O)&Me, ButO' ____+

(MeO),P(: O)OkH,

Examples of the reaction of alkyl and phenyl radicals with alkyl diphenqflphosphinites have been reported.27 t-Butyl radicals were found to initiate the conversion of methyl diphenylphosphinite into methyldiphenylphosphine oxide a4

2L

aa 27

E. H. Poindexter and G. R. Neil, J . Chem. Phys., 1970,52,5648; R. A. Dwek, N. L. Paddock, J. A. Potenza, and E. H. Poindexter, J. Amer. Chem. SOC.,1969, 91, 5437. K. Dimroth, A. Hettche, W. Stade, and F. W. Steuber, Angew. Chem. Internut. Edn., 1969, 8, 770. a J. K. Kochi and P. J. Krusic, J. Amer. Chem. SOC.,1969,91, 3944. Hudson and H. A. Hussain, J . Chem. SOC.(B), 1969, 793. R. S. Davidson, Terrahedron, 1969, 25, 3383.

Photochemistry, Radicals, and Deoxygenation Reactions But' Me'

+ Ph,POMe + Ph,POMe

-----+ Ph,P(:O)But

---+

Ph,P(:O)Me

227

+ Me" + Me'

Decomposition of phenylazotriphenylmethane in the presence of cyclohexyldiphenylphosphinite was found to produce cyclohexene, and the reported evidence is consistent with its formation by attack of a triphenylmethyl radical upon the intermediate phosphoranyl radical (22).

Thermal decomposition of t-butylperoxy esters of cyclohexyl- and phenylphosphonic acids in the presence of styrene initiates polymerisation of the olefin.28 Phosphazenes which have reducible groups attached to the phosphorus can be reduced electrochemically to give phosphonitrilic radical anions in which the odd electron is delocalised in these groups.2* A related finding is that electrochemical reduction of dibenzylphenylphosphine oxide leads to a high yield of dibenzylcyclohexa-2,5-dienylphosphine oxide.30 Alkali metal reduction of 4,4'-diphenylphosphinobiphenyl31 and substituted phospholes32 has been shown to give radicals by e.s.r. spectroscopy, but structures have not been assigned. The preparation and e.s.r. spectra of some phosphorus-substituted picrahydrazyl radicals have been reported.33 The formation of phosphorus-substituted carbenes by decomposition of a-diazoalkyl phosphonates has attracted further attention.34 Several cyclopropylphosphonates [e.g., (23)] have been prepared via these

intermediate^.^^^ Triphenylphosphine has been found to trap carbenes generated from d i a z ~ k e t o n e s ,and ~ ~ nitrenes generated from azides [e.g., (24)].36Other examples of nitrene trapping are in the section on deoxygen28 a0

30

31 3a

3s

34

36

R. C. P. Cubbon and C. Hewlett, J. Chem. SOC.( C ) , 1970, 501. H. R. Allcock and W. J. Birdsall, J. Amer. Chem. SOC.,1969, 91, 7541. L. Horner and H. Newmann, Chem. Ber., 1969, 102, 3953. M. H. H. Noosh and R. A. Zingaro, Canad. J. Chem., 1969, 47,4679. C. Thomson and D. Kilcast, Angew. Chem. Internat. Edn., 1970, 9, 310. K. Lieber, K. Okon, G. Adamska, and E. Bamburski, Roczniki Chem., 1969, 43, 585 (Chem. A h . , 1969, 70, 115,253). a D. Seyferth and R. S. Marmor, Tetrahedron Letters, 1970, 2493; M. Regitz, Angew. Chem. Internat. Edn., 1970, 9, 249; W. Jugelt and D. Schmidt, Tetrahedron, 1969, 25, 5569. J. C. Flemming and H. Shechter, J. Org. Chem., 1969, 34, 3962. E. Zbiral and J. Stroh, Annafen, 1969, 727, 231.

228

Organophosphorus Chemistry

ation of nitro- and nitroso-compounds. Benzyne generated from o-lithiofluorobenzene has been shown to react with triphenylphosphine to give a betaine (25).37 The betaine is protonated by fluorene to give a phosphonium salt and alkylated by methyl iodide to give the methyl-substituted phosphonium salt (26). The betaine can decompose by loss of a phenyl group to give (27).

.,g.. R1'

R2

3 Deoxygenation of Peroxides and Desulphurisation of Sulphides The reactions of chlorodiphenylphosphine with t-butyl peresters s8 and of dialkyl t-butylperoxy phosphates with triphenylphosphine 39 give a variety of products, each in low yield. o-Quinones have been shown to react with triethyl phosphite to give pentaoxyphosphoranes via the cyclic phosphite (28).40 Ascaridole is deoxygenated by triphenylphosphine at a fairly low

s8

89

G. Wittig and H. Matzura, Annalen, 1970, 732, 97. G. Sosnovsky and D. J. Rawlinson, J . Org. Chem., 1969, 34, 3462. G. Sosnovsky, E. H. Zaret, and K. D. Schmitt, J. Org. Chem., 1970, 35, 336. D. B. Denney and D. H. Jones, J. Amer. Chem. SOC.,1969,91, 5821.

229

Photochemistry, Radicals, and Deoxygenation Reactions

temperature (85 "C)to give an epoxide (29).41 Physical evidence in accord with this structure, and not with the previously suggested has been presented. The use of the triphenyl phosphite-ozone adduct as a source of singlet oxygen has been looked at further in order to determine whether the adduct could react with substrate to give the same products as those obtained from reaction with singlet 44 Although the adduct

does not react with r ~ b r e n e it , ~may ~ well be implicated in the reaction with tetrarnethyleth~lene.~~ When the adduct reacted with the ethylene in the presence of 2,5-dimethylfuran, the products obtained suggested that the ethylene is the more reactive of the two compounds. This is just the reverse of that for the reaction with singlet oxygen. Thus, some caution is necessary in interpreting the reactions of the phosphite-ozone adduct as being due to singlet oxygen. The desulphurisation of thiyl radicals by tervalent phosphorus compounds has been utilised in the desulphurisation of cyclic compounds having sulphur bridges.45 Irradiation of the sulphides leads to cleavage of a C-S bond to give a diradical [e.g., (30)]. Intramolecular hydrogen

0

h v ,

( J >-

\G

-/ + o (30)

Q

R,P,

(-J (32)

I;(

R3Pl

P--

a = Hydrogen

Abstraction b

= Desulphurisation

(33)

abstraction may ensue to give a thiol [e.g., (3 l)] which will be desulphurised to give an olefin [e.g., (32)]. The diradical [e.g., (301 may also undergo desulphurisation to give a carbon diradical [e.g., (33)]. Diallylic sulphides are also desulphurised by irradiation in the presence of tervalent phos41 42 43

44 45

G. 0. Pierson and 0. A. Runquist, J . Org. Chem., 1969,34, 3654. L. Horner and W. Jurgeleit, Annalen, 1955,511, 138. R. W.Murray and M. L. Kaplan, J. Amer. Chem. Soc., 1969,91,5358. P. D.Bartlett and G . D. Mendenhall, J. Amer. Chem. Soc., 1970,92,210. E. J. Corey and E. Block, J. Org. Chem., 1969,34, 1233.

230

0rganophosphorus Chernist ry phorus 35S Labelling has been employed to determine the mechanism of desulphurisation, by phosphines, of trisulphides to give dis~lphides.~ Which ~ sulphur atom is extruded is dependent upon the phosphine used. Of the trisulphides studied, triphenylphosphine removes the central sulphur 46 whereas tris(diethy1amino)phosphine removes a terminal sulphur atom.4sb There does not appear to be a simple mechanism to explain this latter result. Thiatriazoles (34) are smoothly desulphurised by triphenylphosphine to give alkyl cyan ate^.^' N-?! Ro(S,N

PhsP

ROCN

+ Ph,PS + N,

(34)

-

4 Deoxygenation of Nitro- and Nitroso-compounds A review of the synthetic applicability of deoxygenation of nitro-compounds as a means of synthesising 5-, 6-, and 7-membered heterocyclic compounds has been p u b l i ~ h e d .Nitrobenzene ~~ is deoxygenated by triphenylphosphine

+

o,+N4 0

6

H,

@;Ph,

H0h/0PPh3 N Ph,P HF

’ F-

6

H

F

F

in anhydrous hydrofluoric acid to give p-fl~oroaniline.~~ Tri-n-butylphosphine does not react. A careful product studys0 has been made of the deoxygenation of o-, m-,and p-nitrotoluenes and related compounds by phosphites. Products included dialkyl N-arylphosphoramidates, dialkyl N-alkyl-N-arylphosphoramidates, and, in some cases, trialkylphosphorimidates and dialkyl-3,4-azepin-7-ylphosphonates.The formation of the 46

47 48

S. Safe and A. Taylor, Chem. Comm., 1969, 1466; D. N. Harp and D. K. Ash, Chem. Cornm., 1970,811. K. A. Jensen, A. Holm, and E. H.-Jensen, Acta Chem. Scand., 1969.23, 2919. J. I. G. Cadogan, Synthesis, 1969, I, 11. P. H. Scott and C. P. Smith, Tetrahedron Letters, 1970, 1153. J. I. G. Cadogan, D. J. Sears, D. M. Smith, and M. J. Todd, J. Chem. SOC.(C), 1969, 2813; J. I. G. Cadogan and R. K. Mackie, J. Chem. SOC.(0,1969,2819. a

Photochemistry, Radicals, and Deoxygenation Reactions

231

latter two compounds is consistent with the formation of a nitrene intermediate. The phosphoramidates are believed to be formed via the phosphorimidates. Such a transformation is most likely under the reaction conditions employed. p-Nitrotoluene, p-ethylnitrobenzene, and p-nitroanisole were found to give substitution products (dialkyl arylphosphonates) in low yield.S0 The substitution reaction also occurs with o-dinitrobenzene.sl The reactivity of the phosphite ester in this reaction is dependent upon its nucleophilicity : the greater its nucleophilic character, the greater its reactivity. A study of the cyclisation of 2-nitro-3’-methylbiphenyl to the two isomeric methylcarbazoles has shown that the relative yield of the two isomers is independent of the phosphite used and of the solvent employed.62 Deoxygenation of 2-nitro-2’,4’,6’-trimethylbiphenylby phosphites results in the formation of the 2-amino-derivative and a phosp h ~ r i m i d a t e . ~That ~ the amino-compound was derived by hydrogen abstraction from the solvent was demonstrated by the formation of bicumyl in respectable yields when cumene was used as solvent. 2-Nitrophenyl 2,6-dimethylphenyl sulphide is deoxygenated by trimethylphosphite to give the azepine (35).64 Confirmation of the postulated mechanism came from a study of the deoxygenation of [4-2H]phenyl 2-nitrophenyl sulphide, in

fJyJ 6,

Me

N: Me

n

51

52

5s s4

J. J. J. J.

I. G. Cadogan, D. J. Sears, and D. M. Smith, J. Chem. SOC.( C ) , 1969, 1314. Sauer and J. Engels, Tetrahedron Letters, 1969, 5175. I. G. Cadogan and M. J. Todd, J . Chem. SOC.(0,1969,2808. I. G. Cadogan and S. Kulik, Chem. Comm., 1970,233.

232

Organophosphorus Chemistry

which [3-2H]phenothiazine(36) was formed.s6 The deuterium labelling in the latter compound was determined by the very neat technique of converting the phenothiazine into its radical cation and examining its e.s.r. spectrum. The position of the label clearly indicates that reaction occurs by way of nitrene attack upon the adjacent benzene ring, followed by a sigmatropic shift. 1,2-Dialkyl-2,3-dihydrobenzirnidazoles(37) have been synthesised by deoxygenation of the appropriate nitro-compound by 0I

\CH2'

trimethyl phosphite.6s In the cited example, preferential attack on the o-nitro-group was observed and it was suggested that this was due to the stabilising effect of the adjacent nitrogen atom. Product studies on the cyclisation of diethyl 2-nitroben~ylidenemalonates,~~ substituted 4-(2nitrophenyl)-l,4-dihydropyridine~,~~ and 6-nitropapaverine 6g have been reported. The deoxygenation of 2-nitrosobiphenyl by triethyl phosphite, to give carbazole, has been the subject of a kinetic investigation.60 The reaction has an activation energy of 11.56 kcal mol-1 and the rate-determining step was found to be the formation of the ionic intermediate (EtO),P-O-fiAr (Ar = biphenyl). Deoxygenation of (38) results in fragmentation of the heterocyclic rings.s1 N-Nitrosoiminobenzothiazolines are deoxygenated to give compounds of the type (39).62 55

s6 67

58

.N

J. I. G. Cadogan, S. Kulik, and C. Thomson, Chem. Cumm., 1970,436. R. Garner, G. V. Garner, and H. Suschitzky, J. Chem. SOC.(0,1970, 825. T. Kametani, K. Nyu, T. Yamanaka, H. Yagi, and K. Ogasawara, Chem. and Pharm. Bull. (Japan), 1969, 17, 2093. T. Kametani, T. Yamanaka, and K. Ogasawara, J . Chem. SOC.(C), 1969, 1616. T. Kametani, T. Yamanaka, K. Ogasawara, and K. Fukumoto, J. Chem. Suc. (C), 1970, 380.

eo e2

J. I. G . Cadogan and A. Cooper, J. Chem. SOC.(B), 1969, 883. J. B. Wright, J. Org. Chem., 1969, 34, 2474. H.-J. Kleiner, Annalen, 1969, 724, 221.

Photochemistry, Radicals, and Deoxygenation Reactions

233

CN

ON p h p z e

(Et0)3P

I

f

PhC=NPh

N’

+ MeCN

-k (EtO),PO

5 Miscellaneous Deoxygenation Reactions A further example which demonstrates that alcohols are transformed into alkyl chlorides with inversion of configuration by treatment with triphenylphosphine in the presence of carbon tetrachloride, is that of the dideuterioalcohol (40)which is convertedto the chloride (41).63The bicyclic alcohol (42) was found to yield two chlorides (44) and (49,and it was suggested that (45) had been formed via isomerisation of the phosphonium compound (43). For orbital symmetry to be preserved in this isomerisation, the lone pair

+

I

D

133

R. G. Weiss and E. I. Snyder, J . Org. Chem., 1970, 35, 1627.

234 Organophosphorus Chemistry of electrons on the oxygen atom must be used [see (46)]. The finding that reacts stereoone isomer of 2-methoxy-4-methyl-1,3-dioxaphosphorinane specifically with neopentyl hypochlorite to give the corresponding phosphate, whereas the other isomer reacts non-stereospecifically, has been explained in terms of the initial formation of pentasubstituted interm e d i a t e ~ .Trialkyl ~~ phosphites react with sulphenyl chlorides of the type (47) to give products which are indicative of the operation of two mechanisms (Schemes 1 and 2).66 Dialkyl phosphites react with thionyl

3 -p ,P-S-P< II

(47)

-

+ I

O-R

0

>PCl + >POR II II S 0 Scheme 2

chloride to give thiopyrophosphates and the reaction appears to involve formation of sulphenyl chlorides of the type (47) which then react with dialkyl phosphite.66 A few examples of the deoxygenation of carbonyl compounds have been reported. Benzoyl cyanide (48) is deoxygenated on heating with triethyl ph~sphite.~' A pentaoxyphospholane is presumably an intermediate. PhCOCN

(EtOhP

(48)

H,C/

30 ' 0

1

Ph(CN)C-;+(CEt),

I

Ph Ph N C T C N

/

Ph(CN)C-C(CN)Ph I \ O\/ EtO/igyEt

1

-

-0 +P(OEt,)

I

I

Ph-C-C-Ph I t CN CN

phXcN Ph

NC

Et I Ph-C-P(OEt)Z I I1 NC 0 V 64 86 66

J. H. Finley and D . B. Denney, J. Amer. Chem. SOC.,1970, 92, 362. J. Michalski and A. Skrowronska, J. Chem. SOC.(C), 1970, 703. R. Zwierzak, Tetrahedron, 1969, 25, 5177. J. H. Boyer and R. Selvarajan, J. Org. Chem., 1970, 35, 1229.

Photochemistry, Radicals, and Deoxygenation Reactions 235 Thiophthalic anhydride gives trans-bithiophthalide on heating with triethyl phosphite whereas reaction with tris(dimethy1amino)phosphine takes a different course, giving (49) and (50).68 Deoxygenation of (51) with triphenylphosphine gives the benzimidazole (52).s0 Diary1 sulphoxides are efficiently deoxygenated by phosphorus trichloride 70 and thionyl chloride gives sulphuryl chloride on reaction with triarylph~sphines.~~ A note has appeared reporting that trialkylphosphines and triarylphosphines are oxidised on reaction with hydr~xylamine.~~ The complicated reactions of triphenylphosphine with benzotrifuroxan have been untangled 73a and the structures of the multitude of products determined.73b

% /

3a_ci 0

0 (49)

(51) 68

70

71

72

73

t 52)

J. H. Markgraf, C. I. Heller, and N. L. Avery, J. Org. Chem., 1970, 35, 1588. M. Sprecher and D. Levy, Tetrahedron Letters, 1969, 4957. I. Granoth, A. Kalir, and 2. Pelah, J . Chem. Soc. (C), 1969, 2424. S. I. A. El Sheikh, B. C. Smith, and M. Z. Sobeir, Angew. Chem. Internat. Edn., 1970, 9, 308. M. D. Martz and L. D. Quin, J . Org. Chem., 1969, 34, 3195. A. S. Bailey, J. M. Peach, C. L. Prout, and T. S. Cameron, J . Chem. Soc. (C), 1969, 2277, 2295; b T . S. Cameron and C. K. Prout, J . Chem. SOC.(C), 1969, 2281, 2285, 2289, 2292.

11 Physical Methods BY J. C. TEBBY

To aid cross-referencing, the order of the sections and subsections has been kept as close as possible to that used in the previous volume. The terms P I I I , PIv, and Pv, etc., have been used when the physical properties of different classes of organophosphorus compounds are being compared and relate to the co-ordination number of the phosphorus atom and not to its valency.

1 Nuclear Magnetic Resonance Spectroscopy All the 31Pand lH chemical shifts are relative to 85% phosphoric acid and tetramethylsilane respectively. lH and 31PN.m.r. parameters of organophosphorus compounds in general have been compiled for use by synthetic chemists.l Although the discussion in Japanese will be a drawback for many, the tables, charts, and references should prove to be very useful. A. Chemical Shifts and Shielding Effects.-The paramagnetic contribution to the shielding of the phosphorus atom has been re-estimated from measurements of spin-lattice relaxation times for POF3.a The contribuis a magnitude smaller than an earlier estimate tion (cp -64Ox (up - 11,793 x which was obtained by comparing calculated and experimental chemical shifts for different molec~les.~ The cyclic phosphines (1 ; R = H or C,H,,) possess 8p 79 and 52 p.p.m. respectively, which are more positive than analogous acyclic phosphines.* The 31Pchemical shift (6p) of (2) is at even higher field (+ 80 p.p.m.) which suggests that the angular restraint (probably ca. 93") has increased the s-character

+

a

+

J. Nakayama, J. Synthetic Org. Chem. Japan, 1970, 28, 177. C. Deverell, Mof. Phys., 1969, 17, 551. M. M. Crutchfield, C. H. Dungan, J. H. Letcher, V. Mark, and J. R. Van Wazer, 'Topics in Phosphorus Chemistry,' J. Wiley and Sons, New York, 1967, vol. 5. P. Tavs, Angew. Chem. Internar. Edn., 1969, 8, 751.

237

Physical Methods

of the lone pair of electron^.^ In contrast, 8p for methyl phosphole (3) is at low field (+ 8.7) relative to divinylphosphines (+ 21 p.p.m.) which is in accordance with a high p-character for the lone pair of electrons., This is supported by the low pKa, highly abundant molecular ion, and pyrrole-like U.V. spectrum of (3). Consecutive large up-field shifts occur as PrI1 substituents are replaced by heavy atoms such as germanium or tin (see Table l).' Phosphorus itself, as in (Ph2P)3P,has a small effect this compound Table 1 Phosphine

Ph,P

SP

+8

Ph2P* SnPh,

PhP(SnPh,)

P(SnPhJ,

+ 56 + 163 +330 p.p.m. possessing signals at + 16.9 and + 27.0 p.p.m. ; note that white phosphorus has 8p + 462 p.p.m. A study of the factors affecting the chemical shift of chalcogenides shows that 8p increases steadily as phenyl groups are replaced by methoxy- or dimethylamino-groups, and the oxides are more deshielded than the sulphides and selenides.* A rather interesting comparison can be made between triphenylphosphine oxide and sulphide with the corresponding carbophosphoranes and trifluorophenyl chalcogenides (see Table 2). The Table 2 Compound

SP Compound

S??

Ph3P+- 0ca. - 26

Ph,P+-C=C-O-

Ph,P+-S-43.9

Ph,P+-C=C-S7.7

- 2.6

+

(C,F,),P+-O-

+ 8.0

(C,F,),P+-S+S.6 p.p.m.

interception of the multiple bond or the substitution of pentafluorophenyl for phenyl1° increases the shielding of the phosphorus atom in both examples, the increase being far greater for the sulphur compounds. That this may be related to pp-dp bonding is indicated by the larger PCC(S) bond angle (168") compared to PCC(0) (145.5")for the carbophosphoranes. Note that the size of the lone pair of electrons on nitrogen in (4) is larger when oxygen is donating (4; Ch = 0) than when sulphur is donating @

a lo

D. Hellwinkel and W. Schenk, Angew. Chem. Internat. Edn., 1969, 8, 987. L. D. Quin, J. G. Bryson, and C. G . Moreland, J . Amer. Chem. SOC.,1969,91,3308. H. Schumann, Angew. Chem. Internat. Edn., 1969, 8, 937. A. Schmidpeter and H. Brecht, Z . Naturforsch., 1969, 24b, 179. C. N. Matthews and G. H. Birum, Accounts Chem. Res., 1969, 2, 373. M. Fild and 0. Glemser, Fluorine Chem. Rev., 1969, 3, 129.

238

Organophosphorus Chemistry

electrons (4 ; Ch = S).ll N-Phosphorylated triethyl- and trialkoxyphosphazines possess values of 8(PlV)which are close to zero,12 slightly upfield of the phosphazine Et3P :NPh (- 14-2p.p.m.); see also this chapter, Section 1B. Two 8p signals are observed in the spectra of the phosphinic esters, acids, and sodium salts ( 5 ) and (6). The separation of the signals is OH I CH2- P -CHz I II I X203P 0 P03X2

CH2-CH- CHY I l l X203P XzPO, P03X,

(5)

considerable since the central phosphorus atom is strongly deshielded by the geminal phosphorus atoms, e.g. - 17.5 and -37-3 p.p.m. for ( 5 ; X = H).13 The chemical shifts are much closer for ( 6 ) and separate signals are observed for the sodium salts only, e.g. ( 6 ; X = Na, Y = H) possesses 2P at -23-5 and 1P at -26.7 p.p.m.14 Only one signal is observed for the acids and esters of (6). The 8p for tri-, tetra-, penta-, and hexa-co-ordinate phosphorus compounds which possess the PClN group have been tab~1ated.l~A number of triphenylcycloalkoxyphosphoranes possessing a saturated ring, e.g. (7; Y = CR, or NR), have been isolated. They have 8p in the region

Y-0

(7)

of + 54( k 7) p.p.m., whilst those incorporating an endo- or em-double bond have 8p + 36( k 2) p.p.rn.ls For di-, tri-, and tetra-alkoxyphosphoranes 8p is +47( k 8) p.p.m.; those possessing two or more methyl groups are in equilibrium with the quasi-phosphonium sa1t.l’ Note that a fifth ethoxy-group, i.e. (EtO):,P, produces a large upfield shift to + 71 p.p.m. Difluoro(pheny1)phosphoranes Ph,RPFz also resonate near this region.l8 Note 8p for PF:, is + 8O-3,lsnot +35-5 p.p.m. as previously believed. A l1 la

l3

l4 l5 l6 l7 l8 I@

C.H.Bushweller and J. W. O’Neil, J. Org. Chem., 1970, 35, 276. V. V. Sheluchenko, I. M. Filatova, E. L. Zaitseva, and A. Ya. Yakubovich, Zhur. obshchei Khim., 1969, 39, 194. L. Maier and R. Gredig, Helv. Chim. Acta, 1969, 52, 827. W. A. Cilley, D. A. Nicholson, and D. Campbell, J . Amer. Chem. Soc., 1970, 92, 1685. H. P. Latscha, P. B. Hormuth, and H. Vollmer, 2. Naturforsch., 1969, 24b, 1237. a R. Huisgen and J. Wulff, Chem. Ber., 1969,102,746; E. E. Schweizer, W. S. Creasy, J. C. Liehr, M. E. Jenkins, and D. L. Dalrymple, J. Org. Chem., 1970, 35, 601. D. B. Denney, D. 2. Denney, B. C. Chang, and K. L. Marsi, J . Amer. Chem. SOC., 1969, 91, 5243. C. Brown, M. Murray, and R. Schmutzler, J. Chem. Soc. ( C ) , 1970, 878. L. Maier and R. Schmutzler, Chem. Comm., 1969, 961.

Physical Methods 239 review of pentafluorophenylphosphorus compounds lo includes a section on & and demonstrates the general upfield shift of the PII1and PIv compounds compared with the phenyl analogues except for (a) the diethylphosphine chalcogenides which have similar chemical shifts, and (b) the penta-coordinated compounds [e.g., (CBFS)3PC12- 105; Ph,PCl, + 10 p.p.m.1 which show the reverse trend. The 19F chemical shifts of a wide range of fluorophenylphosphorus compounds have been used to estimate mesomeric and inductive effects for a wide range of phosphorus groups.2o A similar study has been made using complexes of PI'I ligands with fluorophenylgold.21 The 13Cchemical shift ( 6 ~of ) phosphorus compounds, like &, is directly related to the electronegativity of the substituents. Conversion of a phosphine into its chalcogenide causes a 6 p.p.m. downfield shift of 6~ for carbon atoms separated by one or two bonds from P.22 In contrast, conversion of a phosphine to a phosphonium salt increases the shielding of the adjacent carbon atoms. A rather interesting study of the inductive effects in carbonium ions (by 13Cn.m.r. and CNDO calculations on heats of formation) indicates that an increased amount of positive charge is allowed to develop on a carbon atom which bears a methyl group. It is suggested that the methyl group donates electrons to the empty p-orbital [see (8)], but that this is over-compensated by electron withdrawal from the a - b o n d ~ .A~ ~similar explanation using the empty d-orbitals could apply to phosphonium salts (9).

The lH n.m.r. spectra of isomeric cyclic phosphorus compounds assists the identification of anisotropic effects of phosphorus groups. Thus the 3-proton of the tmns-phosphetan (10) is 0.4-0.7 p.p.m. downfield of the c i s - i ~ o m e r .In ~ ~(11) the methyl group (78-6) is shifted 0-15 p.p.m. downfield relative to the frans-isomer, whereas in the phosphate the methyl group

2o

21 22 a3 24

H. Schindlbauer and W. Prikoszovich, Chem. Ber., 1969, 102, 2914. D. I. Nichols, J. Chent. SOC.(A), 1970, 1216. W. McFarlane, Proc. Roy. SOC., 1968, A306, 185. H. Kollmar and H. 0. Smith, Angew. Chem. Internat. Edn., 1970, 9, 462. S. E. Cremer, Chem. Comm., 1970, 616.

240 Organophosphorus Chemistry (T 8-6) is deshielded in both cis (12; R1 = H, R2 = Me) and trans (12; R1 = Me, R2 = H) isomers.26 The effect is smaller for a similarly placed methyl group in a six-membered ring, e.g. (13) and (14, X = R),2Spossibly because the methyl group is equatorially orientated. In fact the difference is larger when the methyl group is directly opposite on the six-membered Me

Me

ring as in (1 5) 27 and (16),28the methyl group appearing at T 9-01 in (16) and at T 9.11 in the cis-compound. The anisotropic effect of the phosphorus grouping in (17) is small29 although its Pascual constant is probably fairly similar to an alkoxycarbonyl group.

B. Studies of Equilibria and Reactions.-In

contrast to trialkylamines, trialkylphosphines undergo rapid exchange reactions with their trimethylboron and boron trifluoride adducts at ambient ternperat~res.~~ The exchange is slow at - 80 "C. The borane adducts appeared to behave in the opposite manner, but it has since been found31 that both adducts exchange slowly. The exchange process observed was that of benzene solvation and not amine exchange. Thus benzene solvation (and consequently preferential shielding) of the methyl groups was reduced (a) by the addition of amine or an alternative donor such as ether, (b) by raising the temperature (conformer averaging), and (c) by increasing the concentration of the adduct (association instead of solvation). The change in 8p upon co-ordination with borane depends on the P-substituents. Values of 8p for phosphites and aminophosphines move upfield whereas those for phosphines move downfield, which is the same as for oxide formation.32 The boron coupling constants vary very little and it 25 26

28

30

31 33

D. Z . Denney, G . Y . Chen, and D. B. Denney, J . Amer. Chem. SOC.,1969, 91, 6838. M. Mikolajczyk, Chem. Comm., 1969, 1221; Angew. Chem. Internat. Edn., 1969, 8, 51 1 ; M. Mikolajczyk and H. M. Schiebel, ibid., p. 51 1. R. S. Edmundson and E. W. Mitchell, J . Chem. SOC.( C ) , 1970, 752. K. L. Marsi and R. T. Clark, J. Amer. Chem. SOC.,1970, 92, 3791. T. N. Timofeva, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1969, 39, 354. A. H. Cowley and J. L. Mills, J. Amer. Chem. SOC.,1969, 91, 2911. G. E. Ryschkewitsch and A. H. Cowley, J. Amer. Chem. SOC.,1970, 92, 745. G . Jugie and J. P. Laurent, Bull. SOC.chim. France, 1970, 838.

Physical Methods 241 appears that the factor which is changing is the bonding between phosphorus and its substituents. S.C.F.-MO calculations for the phosphineboron adduct indicate there is a relatively small transfer of charge from phosphorus to boron and that back bonding from boron to phosphorus is very 8p is usually shifted downfield relative to the free ligand in complexes with transition metals. The magnitude of the shift is dependent on the geometry and the electronegativity of the metal,34 and phosphorus sub~ t i t u e n t s . The ~ ~ 8p for the trans-complex is often downfield of the ciscomplex for a particular ligand36 although the reverse applies to the palladium complexes (R3P)2PdC12.36 Upon alkylation the 31Pchemical shifts (8,) of phosphine oxides 37 and triaminophosphine selenides38 are shifted downfield (40-50 and 15 p.p.m., respectively). The shift upon complexation of the oxides R,(RO),-,PO with a uranium oxide was closely related to the number of RO groups bonded to p h o s p h o r u ~ .The ~ ~ shift was smallest and slightly upfield for the phosphate, which resembles the phosphite shifts discussed above. Similar observations were made on the fluoroborate complexes of methyl and ethyl phosphate.40 A mixture of tris(trimethy1tin)phosphine and trimethyltin chloride gives only one signal in the 31Pn.m.r. spectrum at 60 OC.' The i.r. spectrum and molecular weight determinations indicate two components and therefore it appears that a very fast exchange reaction is occurring. 31PN.m.r. studies indicate that the PII1and Pv compounds (18) 8p 25 and (19) 8p - 138

+

are interconvertible by heating.41 A similar study of the reaction of trialkylphosphines with chlorophosphines to give chlorophosphoranes showed the intermediate to be the phosphonium phosphine (20).42 A phosphonium salt (21) was also an intermediate in the reaction of PC15 33 34

36 38 y7

yM

s8

40 41

4a

J. Demuynck and A. Veillard, Chem. Comm., 1970, 873. T. H. Brown and P. J. Green, J . Amer. Chem. SOC.,1970,92, 2359. S. 0. Grim and R. L. Keiter, Inorg. Chim. Acta, 1970, 4, 56. S. 0. Grim and D. A. Wheatland, Znorg. Chem., 1969, 8, 1716. D. B. Denney, D. Z. Denney, and L. A. Wilson, Tetrahedron Letters, 1968, 8 5 ; R . G . Weiss and E. I. Snyder, J. Org. Chern., 1970, 35, 1627. I. A. Nuretdinov, N. A. Buina, and N. P. Grechkin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1969, 169. A. M. Rozen, P. M. Borodin, Z. I. Nikolotova, E. N. Sventitskii, and V. I. Chizhik, Radiokhirniya, 1970, 12, 69. J. H. Finley, D. 2. Denney, and D. B. Denney, J. Amer. Chern. SOC.,1969, 91, 5826. H. Germa, M. Willson, and R. Burgada, Compt. rend., 1970, 270, C, 1426. S. F. Spangenberg and H. H. Sisler, Inorg. Chem., 1969, 8, 1006.

242

Organophosphorus Chemistry

with ammonia to give N-phosphorylated phospha~ines.~~ The reaction of PCl, with aliphatic nitriles to give trichlorophosphazines was also followed by 31Pn . m . ~ .The ~ ~ equilibrium between the PIr1and PIv compounds (22) and (23) usually favours the former, but the n.m.r. and i.r. spectra indicate that this trend is reversed when X is donating and Y electron-~ithdrawing.~~ JPHwas then in the range 500-600 Hz. X,P-NHY

X,HP=NY

(22)

(23) (24)

The transfer of hydrogen from cobalt or rhodium to the ortho-phenyl positions of triphenylphosphine and triphenyl phosphite ligands has been followed by lH and slP n.m.r.46 In the case of triphenylphosphine the facile equilibrium between (Ph3P)3PHC1Daand an octahedral complex such as (24) allows the selective ortho-deuteriation of the phosphine. Exchange rates between planar and tetrahedral phosphine complexes of nickel have been studied by line-width analy~is.~'

C. Pse~dorotation.*~-Atopological analysis of polytopal rearrangements A simplified contains a special study of the penta-co-ordinate topological representation of the reactions of R4P+X- and R5P systems has been presented which is fairly readily ~omprehended.~~ Pseudorotation, which has been studied recently by i.r. spectroscopy (see this chapter, Section 3B), is in accordance with the principles of least motion.51 The Berry mechanism of pseudorotation has been tested.52 The 31Pn.m.r. spectrum of (25) at - 100 "C contains a triplet of triplets which changes to

(25) 44 46 46

47 48

49

E.O

sa

A. Schmidpeter and C. Weingand, Angew. Chem. Internat. Edn., 1969, 8, 615. H. P. Latscha, W. Weber, and M. Becke-Goehring, Z. anorg. Chem., 1969, 367, 40. A. Schmidpeter and H. Rossknecht, Angew. Chem. Internat. Edn., 1969, 8, 614. G. W. Parshall, W. H. Knoth, and R. A. Schunn, J. Amer. Chem. SOC.,1969,91,4990; T. Ito, S. Kitazume, A. Yamamoto, and S . Iketa, J. Amer. Chem. Soc., 1970, 92, 301 1. G. N. LaMar and E. 0. Sherman, J. Amer. Chem. SOC.,1970, 92,2691. Erratum: Reference 60 in 'Organophosphorus Chemistry,' 1970, Vol. 1, p. 282 should be: E. L. Muetterties, W. Mahler, and R. Schmutzler, Inorg. Chem., 1963, 2, 613; R. Schmutzler, Angew. Chem. Internat. Edn., 1965, 4, 496. E. L. Muetterties, J. Amer. Chem. Soc., 1969, 91, 1636, 4115. K. E. DeBruin, K. Naumann, G. Zon, and K. Mislow, J. Amer. Chem. SOC.,1969, 91, 7031. 0. S . Tee, J. Amer. Chem. SOC.,1969, 91, 7144. G. M. Whitesides and H. L. Mitchell, J. Amer. Chem. SOC.,1969, 91, 5384.

243

Physical Methods

a quintet at - 50 "C corresponding to frequent pseudorotations. i t is found that the relative rates of broadening and collapse of the various lines are in accordance with a Berry mechanism. The 1°F spectra of trifluoromethyl- and pentafluoroethyl-fluorophosphoranes have been d e t e ~ m i n e d . ~ ~ In contrast to dialkyltrifluorophosphoranes, (F3C)2PF3and (F6C2)2PF3 show only one type of fluorine atom. This could be due to a preference for apical fluoroalkyl groups, which is in accordance with the greater electronwithdrawing power of these groups (see this chapter, Section 3C).54 However, rapid pseudorotation is the more likely reason.65 The first two examples of fluorine atoms constrained to a radial orientation have been 67 In these compounds, (26) and (27),

the stereoelectronic factor which normally guides the fluorine atoms to the apical position is outweighed by the steric preference of two small rings. However, when one of the bridges is tetramethylene (28) the fluorine atom is probably apical.s7 In this compound the stereoelectronic factor, which favours an apical fluorine atom, is increased. First attempts to identify pseudorotation in an arsenic analogue, e.g. (29), suggest that all the processes are very rapid, and even processes which proceed via (30)appear to be fast at - 110 OC.s*

(29)

(30)

.(31)

Tests of the relative importance of stereoelectronic and ring strain effects on the stabilities of oxyphosphorane intermediates (3 1) have been 64 66

63 66

67

68

C. A. Tolman, J. Amer. Chem. SOC., 1970,92, 2953, 2956. 'Organophosphorus Chemistry,' (Specialist Periodical Report), ed. S. Trippett, The Chemical Society, London, 1970, Vol. 1, Chapter 11. J. F. Nixon, J. Inorg. Nuclear Chem., 1969, 31, 1615. M. Becke-Goehring and H. Weber, 2. anorg. Chem., 1969, 365, 185. G. 0. Doak and R. Schmutzler, Chem. Comm., 1970, 476. H. Goldwhite, Chem. Comm., 1970, 651.

Organophosphorus Chemistry

244

devised.6s A process which places a five-membered ring in a diradial orientation has a considerably higher barrier than a process which places an alkyl or aryl group in an apical position. The free energies of activation of these processes are estimated to be of the order 10-17 and ca. 20 kcal mol-1 respectively. It is also concluded that a bulky group in an apical position raises the energy of the phosphorane. Other workers have come to similar conclusions.so Nucleophilic attack tends to occur opposite the bulky group in order to avoid steric compression in the transition state, but once the phosphorane is formed, the bulky substituent will prefer a radial orientation, all other factors being equal. Note that a group in the radial position is adjacent to two 90" bonds whereas a group in the apical position, although slightly further away from phosphorus, is adjacent to three 90" bonds. Other studies in this area have shown that pentaethoxyphosphorane has five equivalent ethyl groups down to -60 oC,61 and that pseudorotation in the cyclic oxyphosphorane (32) is slowed only at - 130 "C when it is 'frozen' in the stereochemistry shown.62 An example of a biscyclophosphorane (33) has the P-methyl groups e q u a t ~ r i a l . ~ ~

Me (33)

D. Restricted Rotation.-The estimation of barriers to rotation or inversion by n.m.r. methods has been reviewed.s4 The general theory and applications are considered. The variable temperature n.m.r. spectrum of the aminophosphine (34) has been rein~estigated.~~ The unsymmetric doublet Me

(34a)

6o 62

6a 64

H

(34b)

D. Gorenstein and F. €3. Westheimer, J. Amer. Chem. Soc., 1970, 92, 634; D. Gorenstein, J. Amer. Chem. Soc., 1970, 92, 644. K. E. DeBruin and K. Mislow, J. Amer. Chem. Soc., 1969, 91, 7393. D. B. Denney and D. H. Jones, J. Amer. Chem. SOC.,1969,91, 5821. F. Ramirez, C. P. Smith, S. B. Bhatia, and S. A. Gulati, J . Org. Chem., 1969, 34, 3385. 5. Ebeling and A. Schmidpeter, Angew. Chem. Internat. Edn., 1969, 8, 674. H. Kessler, Angew. Chem. Internat. Edn., 1970, 9, 219. A. H. Crowley, M. J. S. Dewar, W. R. Jackson, and W. B. Jennings, J. Amer. Chem. Soc., 1970, 92, 1085.

Physical Methods

245

of doublets for the methyl group, which collapses to a doublet upon heating to 88 "C, is attributed to coupling to the NH as well as to P. Thus the extra doubling is absent for the N-deuteriated compound. However, in accordance with the original i.r. evidence,55extensive cooling (- 120 "C) of the deuteriated compound does produce an extra pair of doublets with an intensity ratio of 4 : 1. The more abundant conformer, presumably (34a), has the larger coupling constant (13.9 Hz cf. 4 Hz). The CF, groups would be expected to favour strong P-N p,-d, bonding. Even so, the barrier (ca. 8-5 kcal mol-l) is very low, in accordance with a pm-dminteraction which does not require a specific P-N orientation. The barriers to rotation in formyl- ( 3 3 , acyl-, and aroyl-methylenephosphoranes (36) have been H

A Ph 2P,'-+ PPhz *\

\

Ph3P=CH-CH0

P h3P=CX- CO R

(35)

(36)

I

H C-.C f -';\ MeOzC o+C-OMe (37)

found to be high.66167None of the phosphoranes showed any signs of peak coalescence up to 150 "C, even when strong electron-withdrawing groups (X) at the a-position were opposing delocalisation towards the carbonyl group. The ratio of cis- and trans-conformers in keto- and methoxycarbonyl-phosphoranes changes quite markedly with solvent. Thus the trans-conformer of the cyclic phosphorane (37) is strongly favoured in chloroform, but not in dichloromethane, where the conformer ratio is 1 : 1.6s E. Non-equivalence and Medium Effects.-The proton and deuteron n.m.r. spectra of PH, and PhPD, at 100 MHz and 8 MHz respectively in liquid crystal solution have been determined.69 The study permits the accurate determination of the deuterium quadrupole coupling constant (1 15 rt 2 kHz for PhPD,) which correlates well with bond force constants and atom electronegativities. The above constant is calculated from the nuclear quadrupole splitting (14.8 kHz for PhPD,). This is obtained from the deuterium n.m.r. spectrum and the dipole-dipole splittings (27-3 f 0-5 Hz) of the deuterium atoms with the para-orientated phenyl proton, which is observed in the p.m.r. spectrum. The latter, together with J ~ H also , allows the estimation of the CPD bond angle of PhPD, and the HPH bond angle of PH,. The angles were 96.4 f 1" and 95-3rt 1" respectively.

68

M. L. L. Blanchard and M. G. J. Martin, Coinpt. rend., 1970, 270, C , 1747; H. I. Zeliger, J. P. Snyder, and H. J. Bestmann, Tetrahedron Letters, 1970, 3313, 3317. I. F. Wilson and J. C. Tebby, Tetrahedron Letters, 1970, 3769. M. A. Shaw, J. C. Tebby, R. S. Ward, and D. H. Williams, J . Chem. SOC.( C ) , 1970,

69

B. M. Fung and I. Y . Wei, J . Amer. Chem. Soc., 1970, 92, 1497.

66

67

504.

9

246

Organophosphorus Chemistry

It has been pointed out 7 0 that an inverting N"' or PI'' compound has a periodicity of six rather than three. This means that the non-equivalence introduced by an asymmetric group will be lost when there is rapid inversion. However, this point is presumably invalidated for P-NR, compounds in which the NR2 group is held planar by dT-plrbonding. Such effects are absent in (38) and the PH, protons are predicted to be anisochronous if inversion at phosphorus is slow. Surprisingly, the 100 MHz lH n.m.r. spectrum indicates an apparent chemical shift eq~ivalence.'~ However, substitution of deuterium for one of the PH protons as in (39) removes the second-order effects which cause the apparent equivalence. Thus the PH hydrogens are anisochronous with a very small chemical shift difference and the lHn.m.r. spectrum of (39) contains two overlapping P-H multiplets. Separation was still apparent at 150 "Cand therefore the barrier to inversion is greater than 26 kcal mol-l. Ph \ ,CH--PH, Me

Ph \

CH-PHD

/

Me

Me

OCHMe, P O// 'X \ /

Me

\ /

OR

P

\

SCH, SR

The non-equivalence of the isopropyl methyl groups in (40) does not correlate with any simple property of X,72 but it is noted that an aryl P-substituent is not a prerequisite for magnetic non-equivalence. There appears to be a reduced conformer preference in (40)and (41) in solvents with a high dielectric constant. The changes follow the inverse of the dielectric constant, in agreement with the predictions of an electrostatic model. Methanol as a solvent is an exception, probably because of hydrogen bonding. Also, non-equivalenceis exceptionallylarge in benzene which is typical of aromatic solvents. The solvent shifts by benzene in phosphorylated heterocycles indicate that protons a to the phosphoryl group are deshielded whereas protons further round the ring are shielded.73 The P-H coupling constants of phosphorylated furans and thiophens increase linearly with the dielectric constant of the solvent, the largest shift being for 3&H.74 The magnetic non-equivalence of the a-methylene, and to a lesser extent the B- and y-groups, of n-propyl and n-butyl tertiary phosphine complexes of osmium and rhenium halides is interpreted in terms of a concerted rotation of the alkyl 70

71 72

73 74

'Ib

Note by J. B. Roberts in ref. 71, D. Gagnaire and M. St. Jacques, J. Phys. Chem., 1969,73, 1678. L. Frankel, J. Cargioli, H. Klapper, and R. Danielson, Canad. J. Chem., 1969, 47, 3 167. J. I. G. Cadogan and R. K. Mackie, J . Chem. SOC.( C ) , 1969,2819. H. J. Jakobsen and J. A. A. Nielson, J. Mol. Spectroscopy, 1970, 33, 474. E. W. Randall and D. Shaw, J. Chem. SOC.(A), 1969, 2867.

Physical Methods

247

F. Inversion and Configuration.-Pyramidal inversion has been reviewed.?* The factors affecting inversion were divided into four broad categories; crowding effects, conjugation, angular restraint, and hetero-aromatic substitution. The study of inversion barriers by variable temperature n.m.r. is reviewed.64 The barriers to inversion for a wide range of alkyl and aryl tertiary phosphines are all in the range 29-36 kcal m01-l.~~There was a small but consistent increase in the rate of inversion as the electronwithdrawing power of the substituents increased. The change in rate, which correlates with up is consistent with the view that pn-p,, conjugation stabilises the planar transition state. S.C.F.-MO calculations on phosphine favour the lone pair of electrons in a strongly localised phosphorus orbital consisting of 15% s and 72% p chara~ter.'~Thus PH3 possesses a highly directive lone pair of electrons. The total energy variation during inversion is estimated to be 37 kcalmol-l which is above the range for tertiary phosphines. This is 7 kcal above an earlier e~timate.'~The rate of phosphorus inversion for the isopropylphosphole (42) was determined by a Me

(42)

comparison of the calculated and observed signals for the isopropyl methyl groups. The coalescence at 42-3 "C corresponded to a free energy of activation of 16 kcal mo1-1.80 This is ca. 23 kcal lower than an estimate for a comparable saturated phospholane, giving further support to the concept of conjugative stabilisation of the transition state. Further work on the inversion-rotation process of diphosphines (43) has shown that the free energies of activation are only slightly affected by the nature of the para-substituent on the aryl rings of (43 ; R = p-X C,H4) or even upon replacing the aryl by benzyl groups (43; R = CH,Ph).*l On the other hand, the spectrum of the tetramethyl compound (43; R = Me)

R'

7e '?

'Me

Ph'

A. Rauk, L. C. Allen, and K. Mislow, Angew. Chem. Internat. Edn., 1970, 9, 400. R. D. Baechler and K. Mislow, J. Amer. Chern. SOC., 1970, 92, 3090. J. M. Lehn and B. Munsch, Chem. Comm., 1969, 1327. G . W. Koeppl, D. S. Sagatys, G. S. Krishnamurthy, and S. I. Miller, J . Amer. Chem. SOC.,1967, 89, 3396. W. Egan, R. Tang, G. Zon, and K. Mislow, J. Amer. Chem. SOC.,1970, 92, 1442. J. B. Lambert, G. F. Jackson, and D. C. Mueller, J. Amer. Chem. SOC.,1970,92, 3093.

248

Organophosphorus Chemistry

possessed one triplet only and was invariant over the range - 65 to + 180 "C. Since i.r. evidence favours the presence of a mixture of gauche- and transconformers (see this chapter, Section 3B) it appears that rotation about the P-P bond is fast. The spectrum of the monosulphide (44) which corresponds to a mixture of two racemates is also temperature invariant in the range 100-200 "C. The invariance is attributed to slow P-inversion due to the lack of p,-d, bonding between the two phosphorus atoms. The methyl groups in (45) are also anisochronous and above 65 "Cin benzene solution they collapse reversibly to a singlet.82 The collapse, which is also concentration and solvent dependent, is attributed to an intermolecular exchange reaction. The racemisation of the allylphosphine sulphide (46) at 200 "C ( E , 33 kcal mol-l) occurs via the PIt1intermediate (47). The rearrangement of the thiophosphinite (47) has been followed separately by the rate of attenuation of the methyl doublet (T 8-63) in the n.m.r. spectrum and corresponds to E , 20 kcal m01-l.~~

The optical purity of phosphine oxides of the type (48) may be determined by n.m.r. in a 2 : 1 mixture of ( -)PhCHOHCFS and carbon tetrachl~ride.~~ The two methyl signals from the enantiomers differ by 1.4-3.2 Hz. In the case of (49) another part of the molecule provides the asymmetric

environment and two 8p signals are observed which differ by 4.3 ~ . p . m . * ~ The stereochemistry of alkynols (50) has been established by conversion to allenic phosphine oxides (51), where advantage is taken of the anisotropic effect of the phosphoryl group.86 82

83

84 85

A. H. Crowley and D. S. Dierdorf, J. Amer. Chem. SOC.,1969, 91, 6609. W. B. Farnham, A. W. Herriott, and K. Mislow, J . Amer. Chem. SOC.,1969, 91, 6878. W. H. Pirkle, S . D. Beare, and R. L. Muntz, J. Amer. Chem. SOC.,1969, 91, 4575. H. P. Benschop, D. H. J. M. Platenburg, F. H. Meppelder, and H. L. Boter, Chem. Comm., 1970, 3 3 . A. Sevin and W. Chodkiewicz, Bull. SOC.chim. France, 1969, 4016.

249

Physical Methods

G. Spin-Spin Coupling.-The sensitivity of coupling constants to so many aspects of molecular structure has enabled chemists to probe much deeper into this area of chemistry. However, this very abundance of information has tended to hinder the study of the mechanism of spin-spin coupling. A comparison of coupling between different types of nuclei is made more difficult by the difference in the signs and magnitudes of the magnetogyric ratios. For example, the coupling constants ( J ) for analogous hydrogen and deuterium compounds differ in magnitude for this reason (the sign is the same). This additional complication can be avoideds7 by using the reduced coupling constant K which is defined as KNN’ = J

N N ~ ( ~ ~ /y”), ~ Y N YN =

magnetogyric ratio of nucleus N.

6=h / 2 ~

In general, the coupling constant is dominated by the contact term. This in turn is dominated by the interaction of the nuclear spin (and core electrons) with the atom’s bonding electron(s). When the bonding electron has a considerable s-character the strongest interaction occurs when the core and bonding electrons are antiparallel. This is the case for H-H coupling and coupling involving tetra-co-ordinate phosphorus atoms. When the bonding electrons possess negligible s-character the interaction is by exchange polarisation, for which parallel spins are frequently the strongest interaction e.g., fluorine. These two contributions may be of similar magnitude for P’II compounds where the bonding electrons have a low but significant s-character. Penta-co-ordinate compounds with a trigonal-bipyramidal geometry should also prove to be interesting since the radial bonds are sp2 hybridised and the apical bonds are p d hybridised. Double resonance is used to identify transitions with a common level (i.e. connected transitions). Strong double irradiation of a nucleus will make it undergo very frequent transitions and the second nucleus sharing a common level will experience rapid and opposite perturbations and will be effectively decoupled. Weak double irradiation ‘spin tickling’ will identify connected transitions of two types ( a ) regressive transitions, i.e. those with the same quantum numbers, and (b) progressive transitions, i.e. those with quantum numbers which differ by 2. The former is recognised by the formation of well-resolved doublets, the latter by broadened doublets. A second method of recognising progressive transitions is by Double Quantum Transitions (D.Q.T.).8* A forbidden D.Q.T. (Am = 2) is possible 87

C. C. Jameson and H. S. Gutowsky, J. Chem. Phys., 1969,51,2790; W. M. McFarlane, Quart. Rev., 1969, 23, 187. W. A. Anderson, R. Freeman, and C . A. Redly, J . C‘hem. Phys., 1963, 39, 1518.

Organophosphorus Chemistry

250

if the radiofrequency power is increased gradually above the normal requirement for single quantum transitions. The normal lines become distorted and very sharp lines due to D.Q.T.'s appear half-way between the progressive transitions in the normal spectrum. Rapid exchange processes normally lead to spin decoupling. The factor which determines the extent of spin decoupling is discussed in Section H on paramagnetic effects. (i) J p p and JpIcI. It is expected that lJpp will be positive when the bond has appreciable s-character (e.g. for PIv-Prv coupling). In other cases the sign and magnitude will be variable and in the case of the PIII-PIII coupling may also depend on the orientation of the lone pairs which provide an alternative coupling pathway.89 It is a surprise that lJpp for F,PPF, is negative ( - 3 2 0 HZ),~Obecause a dominant interaction via the P-P bond with appreciable s-character would be expected to produce a positive constant. The coupling between PF, groups through two bonds is of opposite sign,'l e.g. +432 for (52; R = Me) and + 274 p.p.m. for (53). The latter is F, P- NR-PF2

FaP- S-PF,

(52)

(53)

strongly temperature dependent in accordance with large changes in conformer populations. In contrast, only small changes of 2Jpp occur for (52). This may be attributed to an increase in the rigidity of the P-N-P backbone due to P-N dW-p,, bonding which limits the variation of coupling via the lone pairs of electrons. Geminal P-P coupling constants via a metal atom have received considerable attention. Methods of estimating J p ~ pfrom the n.m.r. spectra of Cr, Mo, W, and Pt carbonyl complexes are c~rnpared.'~ J p ~ pis dependent on the metal and the electronegativity of the P-substituents. The generally negative constants for the cis-complexes become more positive (i.e. decrease in magnitude) (a) in the order C r < M o < W and (b) with decreased electronegativity of the P-substituents, whereas the generally positive constants of the trans-complexes increase (a) in the order Cr < W < Mo, and (6) with increased electronegativity of the P-substituents. The signs and trends of 2Jpp for the cis- and trans-complexes of Group VI have been considered by qualitative MO theory and are consistent with a variation of the relative energies of the phosphorus and carbonyl bonding orbitals to the central atom.g3 The small magnitude of J p ~ i phas also been explained by MO theory.g4

eo

ea ea e4

E. G . Finer and R. K. Harris, Chem. Comm., 1968, 110; A. H. Cowley and W. D. White, J. Amer. Chem. Sac., 1969, 91, 1917. R. W. Rudolph and R. A. Newmark, J . Amer. Chem. SOC.,1970,92, 1195. J. F. Nixon, J. Chem. SOC.(A), 1969, 1087. R. D. Bertrand, F. B. Ogilvie, and J. G . Verkade, J. Amer. Chem. SOC.,1970, 92, 1908. F. B. Ogilvie, J. M. Jenkins, and J. G. Verkade, J . Amer. Chem. SOC.,1970, 92, 1916. R. M. Lynden-Bell, J. F. Nixon, and R. Schmutzler, J. Chem. SOC.( A ) , 1970, 565.

Physical Methods

25 1

The linear correlation of lJpw with vco of tungsten carbonyl complexes does not hold when a very wide range of phosphorus substituents is used.OS It is suggested that the coupling is dependent on the s-character of the P-W bond and that there is a rise in positive charge on the phosphorus atom as more electronegative substituents are bound to phosphorus. The relative magnitudes of IJPM for cis- and trans-complexes 36 and their variation with other ligands 34 is also discussed.

(ii) JPF. Strong evidence for ‘through space coupling’ has been presented for the phosphines (54).06 The P-F coupling constants in these compounds are all over 50 Hz, whereas JPF is zero for the meta-trifluoromethyl compounds. As the temperature is raised the coupling constant for (54) also

0

P:

CF,

(54)

Ar ” Ar’

(55)

increases. A similar temperature dependence is observed for (55) and is attributed to an increase in the amplitude of deformation of the phenyl substituents. A much larger increase in coupling is expected as the distance between the coupled atoms decreases compared to the decrease in coupling for a corresponding increase in the interatomic distance. The reduced F-P ‘through space’ coupling constants are a factor of 10 larger than the F-F constant, probably due to the larger size of the P atom. The signs and magnitudes of l J p ~for penta-co-ordinate fluorophosphoranes (56) are negative for both equatorial and apical fluorine atoms, the latter being nearly half the magnitude of the former.07 Note: if the contact interactions to the apical fluorine atom and the apically orientated P-orbital were both dominated by similar exchange polarisations, a positive coupling constant would be expected. The l J p ~for the phosphine (57) is - 873-6 Hz, as predicted.O*

The coupling constants 2 J p ~and l J p ~for (58) show a marked solvent ~ opposite dependence which is linearly related to TPH.OOThe slope for 2 J p is to that for ~ J P H2. J p ~and l J p ~decrease and increase respectively with increasing dielectric constant, which is in accordance with both constants being positive. s6 O6 O7

s8

ss

R. L. Keiter and J. G. Verkade, Inorg. Chem., 1969, 8, 21 15. G. R. Miller, A. W. Yankowsky, and S. 0. Grim, J . Chem. Phys., 1969,51, 3185. H. Dreeskamp, C. Schumann, and R. Schmutzler, Chem. Cumm., 1970, 671. C. Schumann and H. Dreeskamp, Chem. Comm., 1970, 619. R. Fields, M. Green, and A. Jones, J. Chem. Soc. (A), 1969, 2740.

252

Organophosphorus Chemistry

(iii) Jpc. The change in coupling constant on converting a PIrrto a PIv compound is positive for lJpC and negative for 2Jpc.22s looThus for (59) lJpc is - 25 and 2Jp~ is 19.5, and for (60) lJpc is + 50 and ,Jpc is - 5 Hz.lol 989

+

S

II

Me, P Se Me

Me,PSeMe

The trend continues with Pv compounds which possess radial or predominantly radial alkyl groups [lJPcfor (56) is + 128 (n = 3) and +262 (n = l)]. lJpc for (57) is - 34.6 and for MePCl, it is - 45 Hz (the largest value observed so far).lo2 Thus the effects of electronegative substituents on coupling are different for phosphorus and carbon. Either they do not increase the s-character of the remaining bonds or another factor such as rr-bonding is introduced. (iu) IJpH and 2JHp,. There is a progressive increase in from ca. + 200 Hz for phosphines to the region of 550-750 Hz for PIv compounds, and to the region of 700-1000 Hz for penta-co-ordinate compounds. Whereas l J p ~tends to decrease with an increase in electronegativity of the P-substituents in the PIv and Pv series,lo3it is larger for the bis(trifluor0methy1)phosphine (58) ( l J p ~= 216-239 Hz according to the solvent used) 9a than for dimethylphosphine (+ 191 Hz). The geminal H-P-H coupling constant has been determined for a series of PIrrand PIv compounds (61) and (62) by measuring JHPD (taking YH/YD

Q RPHD (61)

X 2 6 H D Hal(62)

-$PHD

6 (63)

as 6.55).lo4 The constant was - 12.5 to - 13.4 Hz for the phosphines, close to zero for the phosphonium salts, but + 35.1 Hz for the sodium salt (63). Apart from the sodium salt, the trend resembles JHCx in that opening of the H-P-H bond angle leads to a more positive constant. ( u ) JPcnH Geminal P-C-H coupling constants of phosphonium salts and phosphine oxides become less negative when the carbon atom bears an electronegative group. Following this trend, an electropositive substituent on carbon, e.g. SiH3, makes the coupling constant more negative.lo5 Thus ~ a The ) constant is much for (64) 2JPCHn(SiHs)= 16 Hz and 2 J p ~ ~ n= (13~ Hz. less in the phosphonate series, e.g. 2 J ~for~ the ~ aethyl compound (65; H. Elser and H. Dreeskamp, Ber. Bunsengesellschuft Phys. Chem., 1969, 73, 619. W. McFarlane and J. A. Nash, Chem. Comm., 1969,913. lo2 J. P. Albrand and D. Gagnaire, Chem. Comm., 1970, 874. l o 3 M. Sanchez, L. Beslier, J. Roussel, and R. Wolf, Bull. SOC. chim. France, 1969, 3053. lo4 S. L. Manatt, E. A. Cohen, and A. H. Cowley, J. Amer. Chem. SOC.,1969, 91, 5919. l o 5 H. Schmidbaur and W. Malisch, Angew. Chem. Internat. Edn., 1969, 8, 372. loo lol

Physical Methods

253

R = Et, X = H) is 7.5 Hz. However, the coupling increases markedly when there is a @-substituent, but then remains remarkably constant (16,9--18.6 Hz) for quite a wide variety of substituents, e.g. (65; R = Me, X = halogen, methoxyl, carbonyl, or nitrile).lo6 On the other hand, the vicinal coupling constant shows the reverse trend: 3 J p is ~ 18 Hz for the ethyl compound (65; R = Et, X = H) but is reduced to 1Cb-14.9 Hz in Et,$CH,SiH,

CI-

(RO) ,PO CH, CH, X (65)

(64)

the @-substitutedcompounds. The latter change is readily explained by a change in conformational populations in favour of the trans-form (66). It is possible that the geminal coupling constant is also dependent on conformation because it is unlikely that the electronegativity of the /3-substituent is the main cause of the increase in 2 J p C H . The magnitude of 2 J p is~ ~ larger still when the a-carbon atom bears two large substituents, as in (67). lo' 0 II (RO), PCHPhCOR H

The n.m.r. spectra of the phosphonates (68) and (69) have provided a series of vicinal coupling constants the magnitude of which is dependent predominantly on the dihedral angle.loS It is found that the angular dependence of J ~ C C has H a Karplus-type relationship. The estimation of JPCCHfor single conformers has been made by comparing it with JHCCH, for which the angular relationship is well estab1i~hed.l~~ In this way, 3433for (70) was estimated to be 6-3 Hz for gauche- and 56-5 Hz for trans-coupling. This is in reasonable agreement with the above work. The vicinal coupling constant is smaller when a carbonyl group is part of the link. There is no difference whether the carbonyl group is a, e.g. H\ /H H

y

C1'

P

kCI,

0

0

(Pr i0)2 PCOCHB

(Me01 2PCR,CHO

II

II

'H (70)

(71)

72)

R. H. Cox and R. B. Adelman, Tetrahedron Letters, 1969, 4017. M. Sprecher and D. Kost, Tetrahedron Letters, 1969, 703. l o 8 C. Benezra, Tetrahedron Letters, 1969, 4471. lo9 A. A. Bothner-By and R. H. Cox, J . Phys. Chem., 1969, 73, 1630. loo lo'

Organophosphorus Chemistry

254

[(71), 3JpH 5 - 5 Hz] ‘lo or P, e.g. [(72), 3 J p 0~ - 4 Hz].lo7 There have been two reports on vicinal coupling constants involving penta-co-ordinate phosphorus; 3JpH is 8-1 Hz for (73) 16a and 12 and 38 Hz for H(A) and H(B) (74).lSb The differences are quite remarkable.

A number of reports on vinyl systems have appeared. Most of the coupling constants fall within the ranges already e~tablished.~~ The geminal constants (24-25 Hz) of the vinylphosphine sulphides (75 ; R = alkyl) ll1 require that the range for the chalcogenides be extended to 5-25 Hz. The reduction of these constants by inductive rather than mesomeric effects of the P-substituents was confirmed by the reduced values 19 and 21 Hz for the P-phenyl compounds (75; R2= Me, R3 = Ph, R1 =!Me or Ph). The cis- and trans-conformers (76) and (77) of formylS

Ph,P+

‘C=C H (76)

/

/

H

\ 0

(77)

(75)

methylenetriphenylphosphorane,66 possessed JpC=24.6 and 19 Hz respectively; the vicinal coupling constant of the trans-conformer was large (38 Hz), in character with the trans-vinylphosphonium salts, but 3JpH (4 Hz) for the cis-conformer was much lower than those for vinyl salts (10-20 Hz). The cis 3JHH was also of a low magnitude. It has been noted65 that the cis-coupling 3 J p ~decreases considerably when the double bond is part of a heteroaromatic ring. The same applies for trans-couplings [5-5 Hz for (78)],112 but is to be contrasted with the corresponding PIv phosphor in^.^^ Evidence has been presented on the aromaticity of 1-rnethylphosphole (79).6 The coupling constants, however, are not greatly dissimilar from systems with less or no claim to aromaticity. Thus JPCHis 38.5 Hz for (79) and 42 Hz for (80), and unless there are some cancelling effects it appears that the orientations of the lone pair of electrons are fairly similar. The vicinal coupling 13.8 Hz is slightly larger than phenylphosphole derivatives (81; R = Me or Ph) but much less than the 110 112

Y. Ogata and H. Tomioka, J . Org. Chem., 1970, 35, 596. A. M. Aguiar and J. R. S. Irelan, J. Org. Chem., 1969, 34, 4030. G. Markl, D. E. Fischer, and H. Olbrich, Tetrahedron Letters, 197Q, 645.

255

Physical Methods

p”h

Q Me

(79)

Ph M eMe0,C 0 2 C o [ T H

FSC

CF3

(83)

MeO,C\ 1 MeOzC Ph

Ph

(84)

30 Hz for trivinylphosphine (82), and considerably larger than that (7 Hz) for the phosphabarrelene (83). These variations have been interpreted in terms of an interaction through the lone pair of electrons.llS The coupling constant is large when the favoured conformations have the lone pair of electrons adjacent to the vinyl group [as in (82)], and 3JpH is small for conformations which minimise this interaction, as in (83). Consequently a configuration in which this interaction was minimal was proposed for phosphorin (84).l13 The geminal coupling constant of the penta-co-ordinate phosphorane (85) is (+) 24.3 Hz.ll* Although the sign was not established experi-

(85)

mentally, it was predicted to be positive from comparative studies utilising well-established trends for changes in hybridisation at the carbon atom. The acetylenic phosphine oxide (86) possesses a vicinal coupling constant of only 2 Hz which is considerably lower than that (9.1 Hz) estimated for acetylene itself, from 3 J of~monodeuterioacetylene. ~ Further reports on the spectra of phosphorylated furans and thiophens have appeared,’**116 which cover a wider range of phosphorus environN. E. Waite and J. C. Tebby, J. Chern. SOC.(C), 1970, 386. E. M. Richards and J. C . Tebby, J. Chem. SOC.(C), 1970, 1425. 116 A. M.Aguiar, J. R. S. Irelan, C. J. Morrow, 5. P. John, and G . W. Prejean, J. Org. 7 Chern., 1969,34,2684. ll@ H.J. Jakobsen and J. A. A. Nielsen, J. Mol. Spectroscopy, 1969, 31, 230. 113

256

Organophosphorus Chemistry

ments. The energy levels for the analysis of the spectra were assigned from double quantum transitions. All the P-H coupling constants were positive. J pH (3) and J P H (for ~ ) (87; Y = S , X = :)* are larger than the corresponding H-H coupling by a factor of 1.25, whereas the corresponding P-H coupling constants for the p-phosphorylated compound (88; X = :) were reduced by

a factor of 0-7-0.95, There was a large difference in 4JpH(5) between the PI'' and PIv compounds. It was 0-65 Hz for the trifuranylphosphine (87 ;Y = 0,X = :) but 2-32-2.87 Hz for the chalcogenidesand methiodide. The difference was considerably larger for the thienyl compounds, 4&H(5) being 0.2 Hz for the phosphine and 4.33-4-82 Hz for the PIv compounds. The other P-H coupling constants did not show this large difference and although no explanation was offered, they may be the first examples of a 'through space' P-H coupling which is transmitted through the lone pair of electrons on oxygen and sulphur. This effect has been proposed for certain types of long-range H-H spin-spin c o ~ p 1 i n g . l The ~ ~ effect is not discernible for the corresponding 2-pyridyl compounds (89);l18 also, the

P-H coupling constants were little different from the corresponding H-H constants for pyridine. There was a linear correlation between all the P-H coupling constants. The constants were positive, except for 4JpH(6). Long-range coupling constants are observed in aliphatic systems when the stereochemistry is favourable. The phosphonate (90) has 4 J 4 Hz ~ llQ ~ and for the phosphine oxide (16) 4 J p is ~ 4.5, cf. 1 Hz for the alternative configuration.28 Multiple bonds, as usual, increase the coupling interaction and (91) has 4&H 6.5 Hz 120 and (92) has 4 J p 4.4 ~ Hz and 5JpH 2 H z . ' ~ 117

118

ll9 120

F. A. L. Anet, A. J. R. Bourn, P. Carter, and S. Winstein, J . Amer. Chem. SOC.,1965, 87, 5249; W. A. Thomas, 'Annual Review of N. M. R. Spectroscopy', ed. E. F. Mooney, Academic Press, London, 1968, Vol. 1, p. 84. H. J. Jakobsen, J. Mol. Spectroscopy, 1970,34,245; G. E. Griffin and W. A. Thomas, J . Chem. SOC.(B), 1970, 477. H. J. Callot and C. Benezra, Chem. Comm., 1970, 485. H. J. Bestmann and R. W. Saalfrank, Angew. Chem. Internat. Edn., 1970, 9, 367.

* The dots represent a lone pair of electrons.

257

Physical Methods Ph,P=CH

;c=c,/H

EtO

COR

(vi) JPOCnHand JPNCnH. The conformational preferences of cyclic phosphates and phosphonates have been investigated further. The n.m.r. and i.r. spectra of a series of phenyl phosphates (93) have been interpreted in favour of a conformational preference for an axial phenoxy-group ;121 the phosphate (94)1(3Jp~(~) 2.8, 3 J p ~ (21 ~ -5 ) Hz) completely favours the conformer shown. The equatorial assignment for the phosphoryl group agrees with the majority of previous conclusions. The conformational populations have been estimated for a series of cyclic phosphonates (95) 27 and cyclic thio-

\

OPh

Me

phosphates (96),122assuming the compounds to be in a conformational equilibrium which may or may not favour one conformation. The measured JPOCH(A) and J ~ O C H (may B ) be expressed in terms of trans- and gauche-coupling constants for the ‘frozen’ conformers and the conformer populations. In the absence of accurate values for Jt,,,, and Jgauche for the compounds studied, the parameter (+.It + &Ig), which was obtained from closely related acyclic analogues, was used to solve the equations. For the thiophosphates Jt,Jg, and the proportion of the major conformer were in the ranges 24-29 Hz, 0-4-3-6 Hz, and 0-8-1.0 respectively. A much wider range of conformer populations was found for the phosphonates. The preferred conformations may be (95) and (96) as drawn. However, there is 121

lz2

J. P. Majoral and J. Navech, Compt. rend., 1969, 268, C , 2117. A. K. Katritzky, M. R. Nesbit, J. Michalski, Z. Tulimowski, and A. Zwierzak, J . Chem. SOC.( B ) , 1970, 140.

258

Organophosphorus Chemistry

still some doubt as to the orientation of the phosphoryl group when the compounds are in solution, which may reflect the absence of proper axial and equatorial orientations on phosphorus due to flattening and broadening of this part of the ring. The very remarkable spectrum of the cyclic phosphite (97) has been analysed using double and triple irradiation.lZ3 The spin-spin couplings,

(97)

which are first-order, support the conformation shown. The proton H(l) is coupled to every other proton in the molecule and also to phosphorus (4JpH(1) 2 Hz), i.e. it is doubled seven times over (128 lines). The n.m.r. spectra of the five-membered heterocycles (98) and (99; Y = C1 or OPh) and their isomers have been analysed.lz4 For (98),

(98)

(99)

varied from 0.25 to 3.0 Hz whereas the range was 0-26-5 Hz for in fact one of the latter couplings for (98) was negative (3JpCNH - 0.25 and 11.5 Hz). Note that a negative 4 J pwas ~ observed ~ ~ for the phosphorylated pyridines (89). The P-N-C-H coupling constants for PIK1 compounds also vary widely: J p N Cis~ 15.3 for (100),12s 9.2 Hz for (101; R = CHzPh), but only 1-4 Hz at 20 "C for (101; R = Ph).lZ6 A conformational effect which is in agreement with the P-N-C-H coupling constants of 13-9 and 4 Hz for the conformers (34a) and (34b) has been 3&0CH

JPNCH;

CJ

\

+

P-N

' c4h

O\

Me

H (. 102)

lZ3

la* 12b

lZe

M. Kainosho and A. Nakamura, Tetrahedron, 1969, 25, 4071. J. Devillers, L. T. Tran, and J. Navech, Bull. SOC.chim. France, 1970, 182. L. V. Vilkov, L. S. Khaikin, A. F. Vasil'ev, T. L. Italinskaya, N. N. Mel'nikov, V. V. Negrebetskii, and N. I. Shvetsov-Shilovskii, Doklady Akad. Nauk S.S.S.R., 1969, 187, 1293. D . C. H. Bigg, R. Spratt, and B. J. Walker, Tetrahedron Leffers,1970, 107.

Physical Methods 259 proposed. The P-H coupling constants for (102) are all of the same sign, probably positive, and favour the conformation 4JpH(A, (0.5 Hz) is smaller than 4&E(B) (which involves a W path) but the reverse may apply to (16).

H. Paramagnetic Effects.-Paramagnetic metals such as Co" and Nil1 greatly decrease the spin-lattice relaxations of the phosphorus nuclei of phosphites.128 Consequently the proton signals which are normally split by phosphorus are decoupled. Large proton chemical shifts did not occur, presumably due to the lack of transmission of unpaired electron density to the region of the protons. Spin decoupling may also be observed in the Ni" complex of dimethyl methylpho~phonate.~~~ However, by varying the temperature and concentration of the metal ion one finds that the PCH, and POCH, spin coupling is not always removed. Thus if nucleus H is coupled to P, the H resonance will not show spin decoupling until the rate of nuclear spin isomerisation of P divided by that of H is comparable to the frequency J ~ H Further, . if H is also coupled to a nucleus X, but with a much smaller coupling constant, then the coupling to X will collapse before the coupling to P. 31P N.m.r. dynamic nuclear polarisation studies of phosphorus compounds have been improved by the use of bi~-diphenylenephenylallyl.~~~ Solutions of the radical with almost any phosphorus-containing compound are stable indefinitely, which allows quantitative measurements to be made. Quantitative 31Pn.m.r. enhancement varies from -650 for (MeO),PO to + 1610 for PC13, the order of increasing scalar interaction being H .c C1< Br < Ph < RO. This order, coupled with the irregular behaviour of thiosubstituted compounds, suggests the operation of both direct and indirect coupling mechanisms, the former related to the electron-nucleus distance of closest approach, the latter to changes in complexation tendencies. Direct coupling with the radical depends on the size of the P-substituents and therefore positive enhancement increases in the order lone pair electrons>H>Cl>Br, and O > S . D.N.P. studies have been extended to phosphonitrilic ring The ultimate 31P enhancements, which were lower than for PIrrcompounds, varied with the added radical in an order similar to that for fluorobenzenes but different from the order for fluorocarbons. There is a general decrease in enhancement as the size of the phosphonitrilic ring increases, which is interpreted in terms of different amounts of electron delocalisation within the rings. Exocyclic chlorine atoms were thought to be primarily responsible for transmitting spin information to phosphorus. 127

188 129

l30 13l

J. P. Albrand, D. Gagnaire, J. B. Robert, and M. Haemers, Bull. SOC.chim. France, 1969, 3496. R. Engel, Chem. Comm., 1970, 133. L. S. Frankel, J . Mol. Spectroscopy, 1969, 29, 213. J. A. Potenza, E. H. Poindexter, P. J. Caplan, and R. A. Dwek, J . Amer. Chem. SOC., 1969,91,4356. R. A. Dwek, N. L. Paddock, J. A. Potenza, and E. H. Poindexter, J. Amer. Chem. Soc., 1969, 91, 5436.

260

Organophosphorus Chemistry

2 Electron Spin Resonance Spectroscopy

Di- and tetra-co-ordinated radicals have been studied in order to obtain information on the stereochemistry and bonding in tri- and penta-coordinated The radicals were produced by dissociative and capture processes respectively, ?rising fr0.m the U.V. irradiation of the PII1 chlorides. Thus PCl, produced PC12and PC14radicals. The e.s.r. spectrum of M e k l , was in accordance with a nearly trigonal-bipyramidal geometry (103) with the unpaired electron in a radial sp2 hybrid orbital; it was

not necessary to invoke 3d orbital participation. The purple radical ion (104) was produced by the action of a sodium-potassium alloy on 4,4'bi~(dipheny1phosphino)diphenyl.~~~ The magnitude of the splittings by the phosphorus atom and ring protons decreased in the order P > H(A) > H(B) > H(C). Phosphonitrilic radical ions have been produced by the electrolysis of (NPPh2)301 p.134 The P atom must bear an aryl group and it appears likely that the unpaired electron is delocalised within a PhPPh unit or, at the most, into a very short adjacent skeletal segment. The e.s.r. spectrum of the phosphorin (105) shows doubling by phosphorus la,l

18.4 G.135 The spectrum is exactly the same for the OCD, compound and therefore delocalisation of the unpaired electron is limited to the ring system. The phospholes (106; R = H or Ph) reacted with potassium in THF or DME to give three groups of signals A, B, and C in the e.s.r. spectrum.136The A signals (a triplet of quintets) and B signals (a doublet of septets) ultimately lead to a nine-line signal C. The signals are believed to be associated with the phenyl groups (probably polymeric) since (a) no

135

G . F. Kokoszka and F. E. Brinckman, J . Amer. Chem. SOC.,1970, 92, 1199. M. H. Hnoosh and R. A. Zingaro, Canad. J. Chem., 1969,47,4679. H. R. Allcock and W. J. Birdsall, J. Amer. Chem. SOC.,1969, 91, 7541. K. Dimroth, A. Hettche, W. Stade, and F. W. Steuber, Angew. Chem. Internat. Edn.,

lS6

1969, 8, 770. C. Thomson and D. Kilcast, Angew. Chern. Internat. Edn., 1970, 9, 310.

132 133

la4

261

Physical Methods

signals are obtained for alkylphospholes, (b) no large doublet due to P-coupling is observed, and ( c ) the same spectrum is obtained for tri- and penta-phenylphosphole. U.V. irradiation of (107) at 77 K gives a doublet which disappears at 156 K.13' It is claimed that the - I effect of the group X (e.g., C1 or MeQ)

reduces the electron density at the carbonyl carbon atom, which has conformational repercussions. y-Radiolysis of trimethyl phosphite at 77 K gave two signals in a 1 : 1 ratio.138 One, an isotropic quartet, was lost at 120 K and is attributed to a methyl radical; the other (a broad singlet at 77, sharp at 120 K) corresponds to the spectrum computed for static and reorientating methylene groups respectively, and is attributed to the radical (108). The small magnitude of the coupling to phosphorus, observable at 120 K, may be due to twisting of the PO(QMe), group out of the nodal plane. Similarly, the methylene radical (log), produced by €4....

,c-

U

0 0 - P II (OMe),

+

Ph3P- CH,

H2C-O-P,

,OMe CRZOH

X-irradiation of the methyltriphenylphosphonium ion, was rapidly reorientating at room temperature but not at 100 K.139 It was unnecessary to invoke considerations of appreciable delocalisation of the electron onto the phosphorus atom. A methylene radical (1 10) was also produced by the action of hydroxy-radicals [generated from hydrogen peroxide and titanium(I1) salts] on dimethyl p h o ~ p h o n i t e s . ~ ~ ~

3 Vibrational Spectroscopy comprehensive A. Band Assignments and Structural Elucidation.-A review of i.r. and Raman data of organophosphorus compounds 141covers the literature up to mid-1968. The simpler compounds are given a theoretical treatment. A useful collection of i.r. data has also appeared in a Japanese j0urna1.l~~The spectra of phosphines containing silicon sub13' 138

13* loo lol 142

K. Terauchi and H. Sakurai, Bull. Chem. SOC. Japan, 1969, 42, 2714. A. Begum, S . Subramanian, and M. C . R. Symons, J. Chem. SOC.(A), 1970, 1334. E. A. C . Luchen and C. Mazeline, J. Chem. SOC.( A ) , 1967, 439. W. Damerau, G. Lassmann, and K. L. Lohs, Z . Naturforsch., 1970, 25b, 152. D. E. C . Corbridge, 'Topics in Phosphorus Chemistry,' ed. M. Grayson and E. J. Griffith, J. Wiley and Sons, New York, 1969, Vol. 6, p. 235. J. Nakayama, J. Synthetic Org. Chem. Japan, 1970, 28, 132.

10

262

Organophosphorus Chemistry

stituents are described,143as are complexes of trialkylphosphines with Group IV tetrahalides144 and Au', Pd", and Pt1'.145 In addition to the expected P-H bands in the 2300cm-l region, the i.r. spectrum of the phosphirane (111; X = H) contained deformation modes at 771 cm-1 (and probably 1020 cm-l),14* whilst phenylphosphine (112; Y = 2 = H) 147 possesses a band at 534 cm-l which is assigned to P-H wagging. The

H\ -C

/i\

PhPYZ

P

P-phenyl absorptions in a series of PII1 compounds (112; Y = Z = Halogen, Me, and H) and (1 12; Z = Ph, Y = C1, Me, and Ph,P) 14' have been assigned in terms of the Whiffen n0tati0n.l~~ Bands in the 520-440 and 430-390 cm-l regions are assigned to the X-sensitive y and t modes (X is PYZ). The t mode, like the r and q modes (at 71&730 and 10701120 cm-l respectively), may be split into symmetric and antisymmetric components, e.g. the spectrum of triphenylphosphine possesses the doublets 698 and 692 (r mode), and 433 and 423 cm-l (t mode). The band at 995-1003 cm-l, assigned to the p ring was thought to be characteristic of phosphonium salts in gene~a1.l~~ However, when a series of PI1' and corresponding phosphonium salts were examined it was found that there was no band which was unequivocally characteristic of phosphonium salts.160It was found best to consider the secondary effect of the phosphonium centre on the normal frequency of bands, e.g. changes in frequency and intensity of P-Me and P-OMe bands. A wide range of t-butyl compounds possessed a band at 820k 15 crn-l.l5l In a series of dichloroalkylphosphines a band of medium intensity appears in the region 1250-1290 cm-l which is assigned to a P-C Bands at 515540 and 567-575 correspond to P-Cl vibrations. The P-0 stretching frequencies of salts of phosphinic and phosphonic acids are dependent mainly on the number of unit negative charges on the group and the bond order of the P-0 group.15o The i.r. spectrum of 143

144 146

146

147 148

14g

160 151

K. D. Crosbie, C. Glidewell, and G. M. Sheldrick, J. Chem. SOC.(A), 1969, 1861; J. Grobe and U. Mollev, J. Organometallic Chem., 1969, 17, 263. I. R. Beattie and G. A. Ozin, J. Chem. SOC.( A ) , 1970, 570. D. A. Duddell, P. L. Goggin, R. J. Goodfellow, M. G. Norton, and J. G. Smith, J. Chem. SOC. (A), 1970, 545. S. Chan, H. Goldwhite, H. Keyzer, and R. Tang, Spectrochim. Acta, 1970, 26A,249. J. H. S. Green and W. Kynaston, Spectrochim. Acta, 1969, 25A, 1677. D. H. Whiffen, J . Chem. SOC.,1956, 1350. G. Witschard and C. E. Griffin, Spectrochim. Acta, 1963, 19, 1905. L. C. Thomas and R. A. Chittenden, Spectrochim. Acta, 1970, 26A,781. P. C. Crofts and D. M. Parker, J . Chem. SOC.(C),1970, 332. E. I. Babkina, J. Gen. Chem. (U.S.S.R.), 1969, 39, 1620.

Physical Methods 263 monomeric dimethylphosphinic acid has been determined by low-temperature matrix is01ation.l~~ The heated vapour is deposited on a cold caesium iodide window simultaneously with a pre-cooled argon matrix at 20 K. The very broad von band which normally dominates the 3000-1500 cm-l region is replaced by a narrow band at 3620 cm-l, and the normally broad vp-0 and vp-0 bands at 1152 and 985 cm-l (in Fluorolube) became very sharp at 1250 and 940 cm-l. The V O H bands of organophosphorus acids in the 3000-1 500 cm-l region are usually in the form of three broad bands, A, B, and C . In a recent attempt to rationalise this formidable region, the sterically hindered di-(2-ethylhexyl)phosphoric acid (1 13) was chosen for study because of its dimeric nature in non-basic s01vents.l~~Comparison of observed and calculated vibrational frequencies suggested that the two high-frequency bands A at 2700-2500 and B at 2400-2100cm-1 are OH-stretching modes and the C band at 1800-1600 cm-1 is an ‘in plane’ bend. The spectrum of dimethylphosphinic acid (1 14) is very similar in this region. ( o E b ) ~ O z H

MezP02H

The shapes, intensities, and frequencies of the VOH bands vary considerably and the very interesting postulation has been made that the ABC type spectra arise wholly or partly from indentations into an otherwise broad V O H The indentation(s) may arise from Fermi resonance when the 260~3(in plane) and/or 2yOH (out of plane) deformations coincide with V O H . The missing intensity is redistributed on either side of the indentation by resonance repulsion. The shape of the band will depend upon, (a) the strength of the Fermi resonance (a strong interaction will make a large broad indentation) and (b) on the frequencies of the bands. ~ centred For the weakly hydrogen-bonded phenyl phosphonic acid 2 8 0 is on VOH and interacts weakly to give two strong A and B bands with a small ~ produces a weaker C band at lower separation, and the lone 2 y o mode frequency. Deuteriated and undeuteriated (1 13) and the indium and gallium salts possess a band at ca. 500cm-1 which varies simultaneously with the antisymmetric vp=O band at cu. 1235 cm-1.16s It is considered therefore that the low-frequency band may also arise from a P=O vibration. The spectrum of dimethylphosphinic acid showed vp=o at 1160 cm-l which may be compared with ca. 1185 cm-1 for phosphinic esters, and 1250 cm-l for the acid monomer in an argon matrix. 153 154

155

lS6

S. T. King, J . Phys. Chem., 1970, 74, 2133. K. Nakamoto, J. R. Ferraro, and G . W. Mason, Appl. Spectroscopy, 1969, 23, 521.

M. F. Claydon and N. Sheppard, Chem. Comm., 1969, 1431. I. A. Vorsina and I. S. Levin, Zhur. neorg. Khim., 1969, 14, 795.

264

Organophosphorus Chemistry

Full assignments have been made for the bands of a series of PrI1and PIv methyltrifluoromethyl compounds (1 15) 15' and N-phosphoryl amides (1 16).158 The secondary effects of phosphorus groups on vc=c 115 vC=o 160 and VNCS 161bands have been noted. Differential i.r. spectroscopy was used to follow the photolytic deoxygenation of benzophenone by triphenylphosphine.162 0 I/ MePYCF,

R,PNH*CORl

B. Stereochemical Aspects.-Molecules such as Me,PF,, MePF,, and PF5 possess trigonal-bipyramidal structures. A comparison of barrier energies for various intermolecular ligand exchange (pseudorotation) processes indicates that a square-pyramidal intermediate arises when the apical bonds are weak and the equatorial bonds are strong [process (a)] whereas a tetragonal-pyramidal intermediate arises when the equatorial bonds are

weak and the apical bonds are strong [process (b)].163 It is of much pertinence, therefore, to arrive at an assignment for the low-frequency fundamental el deformations for these molecules, which could be attributed to an axial bending motion (field A) or equatorial bending motion (field B). This has been a difficult Recent estimates of the mean amplitude of ~~ the apical vibration are best accommodated if Vequatorial< ~ a p i c a 1 . l Whereas bond is expected to be the weaker bond, it is pointed out that the valence shell electron pair repulsion theory would favour a lower bending frequency for the equatorial bonds, since they are repelled and constrained by only two close (90") bonds as opposed to three close (90") bonds for the apical bonds. Strong axial electronegativity effects and significant coupling between the el modes are also cited as evidence. The new evidence is considered 166 to indicate that pseudorotation involves similar amounts of 157 158

A. B. Burg and D. K. Kang, J . Amer. Chem. SOC.,1970,92, 1901. Yu. P. Egorov, Yu. A. Nuzhdina, V. A. Shokol, and G. I. Derkatsch, Zhur. priklad. Spektroskopii, 1969,11, 515; D. L. Hill, M. C. Kirk, and R. F. Struck, J . Amer. Chem.

SOC.,1970, 92, 3208. H. F. Reiff and B. C. Pant, J. Organometallic Chem., 1969, 17, 165. S. E. Ellzey, Canad. J. Chem., 1969, 47, 1251. 161 G. I. Derkatsch and Sh. M. Ivanova, 2. Chem., 1969, 9, 369. 162 L. D. Wescott, H. Sellers, and P. Poh, Chem. Comm., 1970, 586. 163 R. R. Holmes, R. M. Deiters, and J. A. Golen, Inorg. Chem., 1969, 8, 2612. lB4 R. R. Holmes and R. M. Deiters, J. Chem. Phys., 1969, 51, 4043. 156 L. S. Bartell, Inorg. Chem., 1970, 9, 1594. lSfi R. R. Holmes and J. A. Golen, Inorg. Chem., 1970, 9, 1596. 159

160

Physical Methods 265 equatorial and axial bending, as first suggested by Berry. Also the lack of i.r. intensity of the low-frequency fundamental of PF, is reasonably explained by the opposing movements producing only a small net dipolar change during the vibration. The factors affecting pyramidal inversion in PIr1compounds have been reviewed.76 The first example of a mixture of gauche- and trans-conformers has been claimed for the diphosphine (1 17) in the liquid phase.le7 The i.r. and Raman spectra indicated solid (1 17) to be trans. The vibrational S Me,PPMe,

II

YPCI,

X&%Me

spectra of the thiophosphoryl compounds (118; Y = NHMe) and the deuterio-analogues have been analysed, and the doubling of the VPNC and vpCla as well as the v p , ~ bands has been interpreted in terms of restricted rotation about the P-N bond.lss Variable temperature studies on (1 18; Y = OMe) resulted in a similar ~ ~ n ~ l ~ The ~ i bond o n lengths . ~ ~ and ~ angles of (1 19; X = lone pair or 0) have been estimated from the i.r. and Raman spectra.170 C. Studies of Bonding.-The force constants for methylenetrimethylphosphorane have been calculated and compared with those of the corresponding oxide and amine,171 see Table 3. Restricted rotation about the P-CH, bond was also assessed. Linear relationships (a) between the

Table 3 Force constant

Bond order

M~~$-cH,

5.59

1.65

Me36-6 + Me,P-NH,Hal-

6.12

1 *56

9-19

1-96

Compound

force constants Kp-0 and calculated P=O bond energies,172and (b) between vp=o and the corresponding absolute band intensities,173have been reported. In the latter case it has enabled the estimation of the P=O bond moments for a wide range of phosphoryl compounds. Hydrogen-bonding between le7

le9 170 171 173 178

J. R. Durig and J. S. DiYorio, Inorg. Chem., 1969, 8, 2796. R. A. Nyquist, M. N. Wass, and W. W. Muelder, Spectrochim. Acta, 1970, 26A, 611. R. A. Nyquist, W. W. Muelder, and M. N. Wass, Spectrochim. Acta, 1970, 26A, 769. J. Hilderbrand, G. Kaufmann, and R. Rohmer, Compt. rend., 1969, 268, C, 236; J. Hilderbrand and G . Kaufmann, Bull. SOC.chim, France, 1970, 876. V. W. Sawodny, 2. anorg. Chem., 1969, 368,284. H.Schulze and A. Muller, 2. Naturforsch., 1970, 25b, 148. M. A. Landau, A. G. Strukov, and S. S. Dubov, Zhur. strukt. Khim., 1969, 10, 335.

Organophosphorus Chemistry

266

phenol and phosphine deuteriophenol and tri-n-b~tylphosphine,~~~ and phosphonium iodides and methanol 176 has been studied. The i.r. spectra of a series of nickel carbonyl complexes (120) have been examined in dichloromethane Replacement of one of the carbonyl groups of Ni(CO), by a PII1compound causes vco for the remainR,PNi(CO) 3

ing carbonyl groups to decrease. The decrease is greatest for tri-nbutylphosphine and least for PF3. Successive substitutions cause vco to change by nearly constant increments. The notion of d,-p, back bonding, which was originally put forward to explain the low dipole moments, has been generally adopted for explaining the shifts in V C O . However, a fair correlation exists between VCO and Tafts's inductive parameter 0,and the force constants of the P-Ni bond are lower than that expected for a v-bond. The correlation is limited because Taft's CJ is based on the transmission of inductive effects through carbon and not through the more polarisable phosphorus atom. Kabachnik's constant oph 17' is based on the ionisation constants of phosphorus acids and when this is used 54 an excellent correlation is obtained. It is suggested that vco for these complexes may be used as a rapid method of estimating the electron donor-acceptor properties of PIr1compounds, e.g. phosphine is estimated to be intermediate between trimethyl and triphenyl phosphites. The LPL deformation and stretching force-constants vary only slightly between the nickel carbonyl complex and the free ligand.178 However, the interaction of the two P-L bonds is believed to be related to the n-transfer in the Ni-P bond when a P-L n-bond exists, e.g. PF3. Thus the principal stretching force-constant of the Ni-P bond shows a large decrease for the Me3P complex compared to the PF, complex.

4 Microwave Spectroscopy and Dipole Moments Further work on the structure of phosphirans attempts to identify the origin of repulsion between the P-H bond and cis-hydrogens, 179 The trans- and &-isomers, (121) and (122) respectively, were identified from their dipole moments (1.29 and 1.28 D respectively). The methyl group is bent away from the P-H group in the cis-isomer (122) in accordance with Hc.5s9

17* 175

176 177

178

179

B. V. Rassadin and A. V. Iogansen, Zhur. priklad. Spektroskopii, 1969, 10, 524. W. W. Brandt and J. Chojnowski, Spectrochim. Acta, 1969, 25A, 1639. E. V. Ryl'Tsev, I. E. Boldeskal, N. G . Feshchenko, Yu. M. Kovetskii, and Yu. P. Egorov, Teor i eksp. Khim., 1969,5, 563. T. A. Mastryukova and M. I. Kabachnik, Russ. Chem. Rev., 1969, 38, 795. A. Loutellier and M. Bigorgne, J . Chim. phys., 1970, 67, 107. M. T. Bowers, R. A. Beaudet, H. Goldwhite, and S. Chan, J . Chem. Phys., 1970, 52, 2831.

Physical Methods

267

-C

P'

I

/

H

Hc

(i21)

/

H

( 122)

a non-bonded interaction. However, this is contradicted by the nearly identical rotational barriers for the methyl group in the two isomers. It was noted that the rotational barrier is less for the corresponding aziridine and less still for the corresponding oxiran. Therefore the barrier may be related to the geometry of the ring and/or the hybridisation of the ring carbon atoms. The molecular structure of triethyl phosphite and trivinyl phosphite in the vapour phase has been completed.ls0 The bond angles were obtained by including peaks from the 220-280pm region in the calculations. The principal conformer could not be identified. The dipole moments of a series of PIII and corresponding PIv phosphoryl compounds have been determined.ls1 The P=O bond moment decreased with the change of P-substituents in the order R >)) RS )> RO Cl. Microwave spectra obtained from compounds in magnetic fields of around 30,000 G show first- and second-order Zeeman effects from which the molecular quadrupole moments may be obtained.ls2 In this way a comparison of charge distribution may be obtained. Thus PF3 has a large positive quadrupole moment which is decreased in POF3 by the opposing effect of the PO group.

>

5 Electronic Spectroscopy The importance of 3d orbitals on electronic transitions and other physical properties has been examined by semi-empirical MO calculation^.^^^ The agreement between computed and observed properties was improved when the 3d orbit exponent z was included in the basic set but for phosphorus compounds it was relatively insensitive to the precise value of z over a modest range centred at 1-4. The photochemical rearrangements of acetylphosphonates (123) which 0

(123) lS1

L. S. Khaikin and L. V. Vilkov, J. Struct. Chem., 1969, 10, 614. P. Mauret and J. P. Fayet, Bull. SOC.chim. France, 1969, 2363. R. G. Stone, J. M. Pochan, and W. J. Flygare, Inorg. Chem., 1969, 8, 2647. W. W. Fogleman, D. J. Miller, H. B. Jonassen, and L. C. Cusachs, Znorg. Chem., 1969, 8, 1209.

Organophosphorus Chemistry

268

occur in the absence of air in a Pyrex tube support the suggestion that the primary process is an n -+ n* excitation producing a triplet excited state.llo The reaction pathway indicates that rotation about the C-P bond may be restricted by 0-C-P-0 conjugation in the excited state. The U.V. spectra of phosphorus hetero-aromatic compounds show marked similarities with the nitrogen analogues. The bands of the former usually occur at slightly longer wavelength. Thus the spectra of (124; X = P) and

(124; X = N) possess bands at 286 (log E 3.89) and 280 (log E 2.06) respectively,6 and the spectra of (125; X = P) and (125; X = N) possess two bands each at 328 (E 16,600) and 280 ( E 64,500), and 317 ( E 16,700) and 246 nm (E 79,500) respectively.l12 A comparison of the spectra of a wide range of para-substituted triarylbenzylidenephosphoranes (1 26) has shown that conjugation is interrupted by the phosphonium atom.lsa The auxochromic effect of the phosphonium centre in (127; X = Ar,P) was limited and remarkably

(126)

(127)

similar to the effect of nitrile or alkoxycarbonyl (127; X = CN or C02R). In contrast to this relatively weak effect there is a strong mesomeric interaction when the donor group acts through a benzene ring, e.g. (128; Z = CH, or NMe,). In fluorenylidenephosphoranes (129; R = alkyl or aryl) the substituent X has a small influence over the whole The effect is not comparable to the mesomeric interaction in planar pn conjugated systems. Br

(1 29) lS4 lss

G . P. Schiemenz, Communication at the 'Ylide Symposium', Leicester University, July 1970. H. Goetz and B. Klabuhn, Annalen, 1969, 724, 1 .

Physical Methods

269

An attempt has been made to identify, qualitatively, the nature of the .rr-interactions in (1 29) lS6 and in the di-co-ordinated phosphinimine (13O).ls6 The spectra of phosphorus ylides in which the carbanion is part of an extensive chromophoric system have been reviewed.lS7 The olefinic and hetero-aromatic derivatives of the Pv phosphorane (13 1)

possess more-intense absorptions in the 260-300 nm region than bisbiphenylenephosphonium bromide in accordance with the Pv atom being a better auxochrome than the PIv atom.114 Two overlapping sets of 'structured' bands at ca. 265 and 295 nm were attributed to different radial and apical Pv aryl interactions. The photoelectron spectra of phosphine and arsine have been determined and the ionisation potentials calculated.ls8 The electronic spectra of tertiary phosphine complexes continue to be of much interest.lE9 6 Rotation Optical rotation is used extensively in the stereochemical studies of PrlI and PIv compounds and recent work has extended the range to Pv and Pvl compounds. The configurations of triaryl- and trialkyl-phosphine oxides have been correlated by a series of stereospecific interconversions of menthyl phosphinates and phosphine Also, the absolute configuration of a series of phosphonium salts (132) has been established by 0.r.d. Salts Ph, PhHzCCpft

Me

/

B ~ -

Ph.

Me-'$-y /

Prn

(133) lS6

Ia8

lg0

IS1

B ~ -

Ph.

Me,'p-: Pr

/

(1 34)

H. Goetz and B. Klabuhn, Annalen, 1969, 724, 18. A. V. Dormael, Bull. SOC.chim. France, 1969, 2701. G. R. Branton, D. C. Frost, C. A. McDowell, and I. A. Stenhouse, Chem. Phys. Letters, 1970, 5 , 1. L. H. Pignolet, W. De W. Horrocks, and R. H. Holm, J . Amer. Chem. SOC.,1970, 92, 1855; G. J. Leigh and D. M. P. Mingos, J . Chem. SOC.( A ) , 1970, 587; E. C. Alyea and D. W. Meek, J. Amer. Chem. SOC.,1969,91, 5761. R. A. Lewis and K. Mislow, J . Amer. Chem. SOC.,1969, 91, 7009. W. D. Balzer, G e m . Ber., 1969, 102, 3546.

270

Organophosphorus Chemistry

with the configuration (132) or (133) have a large positive Cotton effect at ca. 220 nm. The salts (132) also have a negative Cotton effect at 250280 nm but the salts (133) vary in sign in this region. The corresponding ( + )-phosphines (1 34) have also been examined.lQ2 Trisbiphenyl-2,2'-diylphosphorus(v1) (1 35) can be separated into its enantiomers. Circular dichroism has shown that the (-)-isomer has the

(135) structure (1 35) which resembles a left-handed screw.lQ3The phosphorane (136) has been isolated in its d-, I-, and meso-form~.~~* The relationship between the magneto-optical or diamagnetic contributions and the -rr-characterof the P-0 bond has been improved,lQ5and has been studied, together with molar refraction, in some fluoro-alkoxy compounds (137; X = :) and (137; X = O).lU6The main magneto-optical

factors, such as ionic character and magnetic polarisability, for a fairly wide range of PI'' and corresponding PIv phosphoryl compounds have been studied.lQ7It was found that the magnetic rotation of the P-0 bond increases with the electronegativity of the P-substituents in the order R < C l < O R < F . The Ni-P bond of nickel chloride complexes has also been investigated.lQ8

7 Diffraction X-Ray diffraction of the aminodifluorophosphine (138) at - 110 "C shows the groups at nitrogen to be planar, with one methyl group eclipsed with L. Horner and W. D. Baker, Chem. Ber., 1969,102, 3542. D. Hellwinkel and S. F. Mason, J. Chem. SOC.( B ) , 1970, 640. lS4 J. Ferekh, J. F. Brazier, A. Munoz, and R. Wolf, Compt. rend., 1970, 270, C , 865. P. Castan, M. C. Labarre, and J. F. Labarre, J. Chim. phys., 1969, 66, 1652. lee D. Voigt, P. Swysen, and M. C. Labarre, Bull. SOC.chim. France, 1969, 3383. 19' P. Cassoux, P. Castan, P. Swysen, M. C. Labarre, and J. F. Labarre, J. Chim.phys., 1969, 66, 1770. Is* P. Cassoux and J. F. Labarre, J . Chim. phys., 1969, 66, 1420; J. M. Savariault, P. Cassoux, and J. F. Labarre, J. Chim. phys., 1970, 67, 235. lS2

lS3

27 1

Physical Methods j;P,

Me I

.I./N\Me

*I*,Cfi

'B

/

Ph

Ph

P

P

F/

/C

Ph/

'Ph

the phosphorus lone pair of The P-N bond length (163 pm) is much shorter than the sum of the covalent radii for P-N (178 pm) but similar to that for P=N (164 pm). Also, the PNC bond angle is just over 120". The stereochemistry has a bearing on n.m.r. studies (see Section 1D). A more refined structure determination of the diphosphineacetylene (139) shows that the lone pairs of electrons are at 90" and the P-C(sp) bond length is slightly shortened.200 One may ponder whether conjugation of the PrI1 atom with different acetylenic r-bonds is responsible for the stereochemistry. The major isomer of the phosphetan (140) is trans and not cis.24 In previous work, the crystals of superior form, which were selected for study, turned out to be those of the minor component. The phosphole dimer (141)

has a more strained CPC bond at the bridge (87")than the CPC bond in the endo-fused ring.2o1 The accuracy of the structure determination was considerably improved by cooling to -40 "C. In six-membered rings, e.g. (142) 202 and (143),203the CPC bond angles (104"and 102"respectively) are similar to the OPC angles of dioxaphosphorins. In (143) the bond angles involving sulphur are increased from tetrahedral up to 116". This is attributed to the large sulphur atom being relatively close (195 am) to the

E. D. Morris and C. E. Nordman, Inorg. Chem., 1969, 8, 1673. J. C . J. Bart, Acta Cryst., 1969, 25B,489. 201 Y . H. Chiu and W. N. Lipscomb, J. Amer. Chem. Soc., 1969, 91, 4150. 2 0 2 IMazhar-ul-Haque, J . Chem. SOC.(B), 1970, 711. 2 o s J. D. Lee and G. W. Goodacre, Acta Cryst., 1970, 26B,507. lB8

2oo

272

Organophosphorus Chemistry

phosphorus atom. The intermolecular P.. , ...S distance (347 pm) is also small and provides additional evidence that the van der Waal's radius of sulphur should be less than the Pauling (1960) value of 185 pm. Even accepting the suggested smaller value of 172 prn and adding this to the 190pm radius for phosphorus, the contact is still short. Decreasing the ring size to five-membered, as in (144), has surprisingly little effect on the P-P and P=S bond length^.^^^ A similar P=S bond length occurs in (145).205

(1 44)

(1 45)

X-Ray diffraction studies on the phosphinimine (146) 206 show that the PNC bond angle is 119" in accordance with an sp2-hybridisednitrogen. The dihedral angle (55-3") between the methyl and phenyl groups [see (147)] does not correspond to the most staggered conformer, cf. methylenetriphenylphosphorane (148).207The P-N bond in (146) (164 pm) is almost as long as in methylenephosphoranes and somewhat longer than expected; F

H

Ph

P Ph,P -N

+ -

N-PPh, N (149)

note, the P-N bond is 153 pm in (149).,08 Electronegative substituents generally tend to lengthen the remaining bonds to an atom, but the P-N bond is usually an exception because electron withdrawal from phosphorus promotes v-bonding and shortens the P-N bond, e.g. 160 for (Me,PH),, 157 for (Cl,PN),, and 151 pm for (F,PN)4.209It is possible that in (146) P-F n-bonding is competing with P-N rr-bonding. 204 205

206

207

208 209

J. D. Lee and G. W. Goodacre, Acta Cryst., 1969, 25B,2127. J. D. Lee, G. W. Goodacre, S. C. Peake, M. Fild, and R. Schmutzler, Naturwiss., 1970, 57, 195. G. W. Adamson and J. C. J. Bart, Chem. Comm., 1969, 1036. J. C. J. Bart, J. Chern. SOC.(B), 1969, 350. T. S. Cameron and C. K. Prout, J. Chem. SOC.(C), 1969, 2281. A. W. Schlueter and R. A. Jacobson, J . Chem. SOC.( A ) , 1968, 2317.

Physical Methods

273

The phosphinimine (149) is rather interesting because the crowding round the central phenyl ring prevents the nitro-groups from conjugating with the ring.208Delocalisation of the negative charge into the central ring will also be limited by the presence of three such groups on the ring, consequently the P-N bond length of 153 pm is probably the result of considerable back-bonding to phosphorus. The reaction of triphenylphosphine and benzotrifuroxan also produced several other interesting compounds.210In the stabilised phosphinimine (150) the P-N bond (163 pm) is lengthened because the negative charge is extensively delocalised by the nitroso-group.211 Notable is the way in which the electron-rich oxygen atom turns away from the phosphonium centre, avoiding what would appear to be a stable six-membered ring incorporating an ionic bond. Possibly such P+...O- bonding would require the phosphorus atom to possess considerable trigonal-bipyramidal geometry, which in turn would require the nitrogen and oxygen atoms (for reason of bond angles) to occupy unfavourable radial orientations. \When the phosphorus and oxygen atoms are separated by two atoms the electrostatic attraction may be appreciable because in (151) they are only 301 pm apart.212 The P-Cbond length (177 pm) is almost as long as the P-C (phenyl) bonds (179-0

9,

’0,


210

211 212

Ph,P w

I

N N ‘0’

’

P

h

3

N N ‘0’

A. S. Bailey, J. M. Peach, C. K. Prout, and T. S . Cameron, J. Chem. SOC.(0, 1969, 2217. T. S. Cameron and C. K. Prout, J . Chem. SOC.( C ) , 1969, 2285. A. S. Bailey, J. M. Peach, T. S . Cameron, and C . K. Prout, J . Chem. SOC.( C ) , 1969, 2295.

274

Organophosphorus Chemistry

182 pm), which is in character with the decreased necessity for backdiphosphorane (152a) force both of the six-membered rings to take up a boat-shaped geometry [see (152b)].213The P-C (methylene) bonds at either end of the molecule appear to be non-equivalent (171 and 177 pm) which may mean that the anion is better delocalised at one end of the molecule than at the other. The adjacent pairs of C-C bonds reflect this difference, being longer (145 and 149 pm) and shorter (both 143 pm) respectively. There is, however, no noticeable lengthening of the C-N bonds. This is characteristic of these types of bonds. The stabilised methylenephosphorane (153) has a cis-geometry but is twisted 33" out of plane by steric This does not prevent extensive delocalisation as shown by the long P-C (methylene) bond (175 pm) and the short central C-C bond (141 pm). - I - \

Phs P

N-~CN

\

/

/

\

c=c

Me0,C

Me

C02Me

6

Me

The full report on the structure of the phosphorin (154) included the methyl hydrogen atoms in the analysis.216Without these, the C-Me bond lengths were unduly long. The crystal structures of the two PIv phosphorins (155) 216 and (156) 217 have also been determined. The C5P rings deviate slightly but significantly from planarity. The ring CPC bond angles are wider, 104.7" in (155) and 107" in (156), compared to that in Ph

Ph

0

Ph

i\

Ph

6

Ph

\Pn:

Me Me

M e 0 OMe

(155)

(156)

(154). This requires the CCC bond angles at the p-positions to open to ca. 127". The latter changes are unlikely to be of great significance and are probably a geometrical necessity. In (156) the methoxy-groups are forced together, the OPO angle being only 93". The electron diffraction spectrum of (157) has been reported.21*The P-0 213

al* 216

a17

B18

T. S. Cameron and C. K. Prout, J. Chem. SOC.(C), 1969, 2292. R. Huisgen, E. Brunn, R. Gilardi, and I. Karle, J . Amer. Chem. SOC.,1969, 91, 7766. J. C. J. Bart and J. 5. Daly, J . Chem. SOC.(A), 1970, 567. J. J. Daiy and G . Markl, Chem. Comm., 1969, 1057. U. Thewalt, Angew. Chem. Internat. Edn., 1969, 8, 769. V. A. Naumov, N. M. Zaripov, and V. G. Dashevskii, Doklady Akad. Nauk S.S.S.R., 1969,188, 1062.

Physical Methods

275

bond lengths are ca. 6 pm longer than the corresponding bonds in (158).219 The bond angles in the ring of (1 58) are all normal, so that the ring is fairly strain-free. The ring is more nearly planar than a cyclohexane chair conformation, which is probably the result of the 120" POC bond angles and possibly the result of a reduction in non-bonded interactions. The structures of adenosine triphosphate (ATP) 220 and guanosine 5'-phosphate 221 have been determined. The hexavalent phosphate (159)

possesses an octahedral phosphorus atom,222and a planar four-membered ring in which the P-N bond is very long (190 pm). This could be partly due to the absence of P-N n-bonding and further demonstrates the flexibility of the P-N bond lengths in general. 8 Electrochemical Studies The anodic behaviour of tertiary phosphines and diphosphines has been investigated by voltammetric and polarographic methods using a carbon paste The half-wave potential decreases as P-phenyl groups are replaced by alkyl groups or phosphine groups, as shown in Table 4. Only a limited number of secondary phosphines were examined but if they are treated as a separate group a similar trend is observed. Cathodic reduction 224 and further work on the polarography of phosphonium salts have also been

z2*

221

228

224

226

Mazhar-ul-Haque, C. N. Caughlan, and M. L. Moats, J. Org. Chem., 1970, 35, 1446. 0. Kennard, N. W. Isaacs, J. C. Coppola, A. J. Kirby, S. Warren, W. D. S. Motherwell, D. G. Watson, D. L. Wampler, D. H. Chenery, A. C. Larson, K. A. Kerr, and L. R.. Di-Sanseverino, Nature, 1970, 225, 333. W. Murayama, N. Nagashima, and Y. Shimizu, Acta Cryst., 1969, 25B, 2236. M. L. Ziegler and J. Weiss, Angew. Chem. Internat. Edn., 1969, 8, 455. H. Matschiner, L. Krause, and F. Krech, Z. anorg. Chem., 1970, 373,l. H. Matschiner, A. Tzschach, and A. Steinert, 2. anorg. Chem., 1970, 373, 237. L. Horner, I. Ertel, H. D. Ruprecht, and 0. Belovsky, Chem. Ber., 1970, 103, 1582.

276

Organophosphorus Chemistry

Table 4 Halfwaue potentials (mV) Phosphines Ph,P 1000 Ph,PH 990 ca. 950 Ph,PR PhPHBu 915 ca. 900 PhPR, PR3 ca. 865 Et,PH 845

Diphosphines Ph,P. PPh, 915 PhEtP. PEtPh 845 ca. 755 R2P* PR, (But),P * P(But), 685

9 Mass Spectrometry Phosphinidene ions, which are common to the spectra of most phenyl compounds (triphenylphosphine oxide is one 113 are also found in the spectra of pentafluorophenylphosphines.l*,226 The corresponding pentachlorophenylphosphinideneion is absent from the spectrum of (C&15)3P but the ion C6c&P+is present. Similar ions (C6H,P+) can be identified in the spectra of phenyl compounds but not the pentafluorophenyl compounds. Methyl phosphinidene ions are formed, in low abundance, from cyclopentarnethylphosphine at 900 0C.227 Further studies on j3-oxoalkylidenetriphenylphosphoranes have been 229 It has been confirmed that the ion corresponding to triphenylphosphine oxide (160) does not arise from oxide impurity. Thus Ph,PC RICO,R -I’

+

Ph,PCRCO2

l*

Scheme 1 (“metastable ion observed) 221 228

22g

A. T. Rake and J. M. Mlleir, Org. Mass Spectrometry, 1970, 3, 237. H. F. Grutzmacher, W. Silhau, and U. Schmidt, Chem. Ber., 1969, 102, 3230. A. P. Gara, R. A. Massey-Westropp, and J. H. Bowie, Austral. J. Chem., 1970, 23, 307. R. T. Aplin, A. R. Hands, and A. J. H. Mercer, Org. Mass Spectrometry, 1969, 2 , 1017.

Physical Methods 277 the ion was present in spectra run at a source temperature which would not produce a molecular ion from triphenylphosphine oxide. Its mode of formation from the ketophosphorane (161) is viu loss of acetylene, but for the ester phosphoranes (162) it is formed in two consecutive steps-loss of R and the loss of RCCO (see Scheme 1). The bridged hydroxyphosphonium ion (163) is believed to arise by two paths, one by the triphenylphosphine oxide radical ion (160), the other from the M - 1 bridged ion (164). Another ion which owes its genesis to P-0 bond formation is (165). Rather unusual hexavalent structures are drawn for the molecular ion.228 Since the stable phosphoranes are enolates (166) a molecular ion with a similar structure such as (1 67) and/or the cyclic structure (168) would be more acceptable. 4-

.; I o.;;'c

Ph3P-CR1 \

Ph3P-CR1 +o&, ;I

I

R

R

The bis-biphenylenephosphorus compound (1 69) shows a doublycharged parent ion which is many times more intense than the singly-charged It is assumed that the latter fragments rapidly, whereas the former

P

\

(169)

+. P

\

8'8 ( 170)

rearranges to the tervalent ion (170). The very abundant Mf and ( M - 1)+ ions for methylphosphole have been cited as evidence for its heteroaromatic character.* The mass spectrum of trimethylphosphine has been re-examined under conditions which favour the observation of metastable ions.231 Loss of H2 is a common feature of the fragmentations following 230 231

D. Hellwinkel and C. Wunsche, Chem. Comm., 1969, 1412. R. G. Gillis and G. J. Long, Org. Muss Spectrometry, 1969, 2, 1315.

278

Organophosphorus Chemistry

the initial loss of either a hydrogen atom to give Me2PCH2+or a methyl radical to give Me,Pf. A remarkable rearrangement links three carbon atoms to give C3H5+. Ionisation potentials and bond energies have been estimated from appearance potentials of primary, secondary, and tertiary aliphatic phosphines and d i p h o s p h i n e ~ .The ~ ~ ~intensities of the a-,p-, and rr-ions are rationalised and the latter are compared with #3-eliminations of organic chemistry. The mass spectra of the dimethyl and diethyl esters of the acids of general structures (171) and (172) respectively all show

y

(171)

=Y

ch MeO,

,Ch P’ MeO’ +-

Ch

A

(MeO), P+

Scheme:;!

( M - X ) ions.233The methyl esters also fragment by loss of formaldehyde, whereas the ethyl esters tend to lose C , and C , carbon fragments such as methyl, ethylene, acetaldehyde, and C,H, (see Scheme 2). The last radical (173) is believed to arise from a double hydrogen rearrangement as shown.

FH2

X / \O-CH

“I:

-

EtO,

,OH

?fP%H

+

~H=CH, ( 1 73)

The relative importance of the fragmentation pathways of the dimethylaminophosphines (174) and (175) depends on the halogen atom. The ratios of the rates ajb and cld increase in the order F < C1c B r and probably reflect the relative strengths of the P-halogen bonds234(see Scheme 3). There was a high abundance of immonium ions in general. 23a

233 234

G. M. Bogolyubov, N. N. Grishin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1969, 39, 1772. J. G . Pritchard, Org. Mass Spectrometry, 1970, 3, 163. W. Z. Borer and K. Cohn, Analyt. Chim. Acta, 1969, 47, 355.

Physical Methods

279 (Me,N), PHal

- - - _+_ _ _ _ _ _ _ Me,N-P-NMe,

Me,NPHaI,

+

+

Me,N=-P- Hal Scheme 3

C2H5Nx-PHa12

Mass spectrometry by ion cyclotron resonance (I.C.R.) has been used to compare the bond strengths and basicities of phosphine and ammonia in the gas phase.235 The proton affinity of phosphine was 22 kcal mol-1 less than that of ammonia. This is similar to their difference in water and therefore solvation probably plays a minor r61e in their relative basicities in water. A recent comparative study of the basicity of amines and phosphines attributed the differences to e n t h a l ~ y .The ~~~ acidity of phosphine, estimated by I.C.R., is ca. pK 20.237 I.C. R. spectroscopy involves the transfer of ions generated by electron bombardment to a resonance region where a magnetic field of ca. 5 kG is applied. The ions enter circular orbits whose angular frequency is dependent upon the mass of the ion and the applied field. The ions are detected by irradiation in the region of 200 kHz. The technique is very useful for the study of ion-molecule reactions since double irradiation at the cyclotron frequency of a parent ion P + heats the parent ion and causes an increase in the absorption energy of its daughter ion D+. In this way an ion-molecule reaction such as P+ + M 1 -+ D+ + M 2 can be identified and then Triniethylsilyl derivatives of phosphonylethanolamine and phosphorylethylamine have been separated by g.1.c. and subsequently analysed by This is superior to earlier methods of identifying mass natural phosphoric and phosphonic acid derivatives. The method may be applied to the structure elucidation of phosphorus containing complex lipids of membrane origin. Combined g.1.c.-mass spectral analysis of silylated nucleotides and monosaccharides 240 has been extended to phosphorylated carbohydrate^.^^^ The phosphates of an aldo- and keto-hexose, an aldopentose, and a phosphohexanoate give unique ions which may be used for the detection and measurement of trace amounts of these compounds. 236

236 237

238

D. Iioltz and J. L. Beauchamp, J . Amer. Chem. Soc., 1969, 91, 5913. H. J. Hilderson, Mededel. vlaam. chem. Ver., 1968, 30, 173. J. R. Eyler, Inorg. Chern., 1970, 9, 981. J. L. Beauchamp, L. R. Anders, and J. D. Baldeschwieler,J. Amer. Chem. SOC.,1967, 89, 4569.

239 240

K. A. Karlsson, Biochem. Biophys. Res. Comm., 1970, 39, 847. J. A. McCloskey, A. M. Lawson, K. Tsuboyama, P. M. Krueger, and R. N. Stillwell, J . Amer. Chem. Sac., 1968, 90, 4182; D. C . Dejongh, T. Radford, J. D. Hribar, S. Hanessian, M. Bieber, G. Dawson, and C. C. Sweeley, J. Amer. Chem. Soc., 1969, 91, 1728.

241

M. Zinbo and W. R. Sherman, J. Amer. Chem. SOC.,1970,92,2105; J . J. Dolhun and J. L.Wiebers, J. Amer. Chem. SOC.,1969, 91, 7755.

280

Organophosphorus Chemistry

10 pK, Reaction Rate, and Thermochemical Studies The application of the Hammett equation to organophosphorus reactions and equilibria has been reviewed.177 Linear correlations may be obtained when the phosphorus atom is not a reaction centre. However, for reactions involving the phosphorus atom directly it is necessary to use special inductive oFh and resonance ugh constants. Comparative rates of acid hydrolysis of phosphetan amides (176; X = NMe,) and chlorides (176; X = Cl) 242 and the rates of alkaline hydrolysis of methyl ethylenephosphate 243 (177) have been used to test pseudorotation theories.

( 176)

(177)

The isotope effect on the acetolysis of phosphonium salts (178) has been carried out on samples using only the natural abundance of heavy isotopes (13C and 180).244 This was done by comparing the isotopic content of carbon dioxide evolved during complete hydrolysis with that from similar samples undergoing a known fraction of solvolysis. Another interesting technique was applied to a study of the reaction of uridine phosphates with the enzyme r i b o n u ~ l e a s e . The ~ ~ ~kinetics of the reaction were determined from the changes in pH and U.V. absorption produced by temperature jumps of 7-5 "C. The pKLs of a wide variety of weak bases, including triphenylphosphine oxide, have been determined from their heats of i ~ n i s a t i o nComparative .~~~ studies of the basicities of amines and phosphines were discussed in Section 9 of this chapter. The problem of determining the PKa of l-methylphosphole, which polymerised in acid, like pyrrole, was circumvented by plotting the U.V. absorbance of the free base with time, at different acid concentrations.'? The pK, was estimated to be 0-5 from parameters obtained after extrapolation back to zero time. The PKa's of mono-, tri-, and tetra-phosphinic acids are also r e ~ 0 r t e d .l4, l ~247 ~ The heats of formation of tributyl phosphite, tri-n-hexylphosphine, and its oxide have been determined and values for other phosphorus compounds were 24a

24s

244 345

246 247

f48

P. Heake, R. D. Cook, T. Koizumi, P. S . Ossip, W. Schwarz, and D. A. Tyssee, J . Amer. Chem. Soc., 1970, 92, 3828. R. Kluger, F. Covitz, E. Dennis, D . Williams, and F. H. Westheimer, J. Amer. Chem. SOC.,1969, 91, 6066. S. Seltzer, A. Tsolis, and D. B. Denney, J . Amer. Chem. SOC.,1969, 91, 4236. G. G. Hammes and F. G. Waltz, J . Amer. Chem. SOC.,1969,91,7179; E. J. del Rosario, and G. G. Hammes, J . Amer. Chem. SOC.,1970, 92, 1750. E. M. Arnett, R. P. Quirk, and J. J . Burke, J . Amer. Chem. SOC.,1970, 92, 1260. V. E. Bel'Skii and G. Z. Motygullin, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1969,2047. A. V. Nikolaev, Yu. A. Afanas'ev, and A. D. Starostin, Izuest. sibirsk. Otdel. Akad. Nauk, S.S.S.R. Ser. khim. Nauk, 1968, 3.

Physical Methods

28 1

11 Surface Properties Chromatography on silica allows the rapid analysis and separation of a wide range of PI'' and PIv organophosphorus corn pound^.^^^ Solvent mixtures of hexane, acetone, ethyl acetate, and t-butanol are useful eluants in thin-layer and a molybdic-perchloric reagent has been used for developing the chroma tog ram^.^^^ Excellent separation by g.1.c. of chlorophosphines has been achieved using Apiezon L on Celite 545 or Chromosorb Osmotic coefficients of phosphonium partition coefficients of diphosphine and the development of a phosphonic acid cationexchange resin 255 have also been reported. 249 250

251 252

253 25* 255

C . Gonnet and A. Lamotte, Bull. SOC.chim. France, 1969, 2932. A. Lamotte and J. C . Merlin, J. Chromatog., 1969, 45, 432. A. Lamotte, A. Francina, and J. C . Merlin, J. Chromatog., 1969, 44,75. A. G. Shostenko, P. A, Zagorets, and A. M. Dodonov, Trudy Moskov. Khim. Tekhnol. Inst., 1968, 242. I. J. Gal, 1. Paligoric, and V. G. Antonijevic, J. Inorg. Nuclear Chem., 1970, 32, 1645. J. W. O'Laughlin and D. Jensen, Analyt. Chem., 1969, 41, 2010. Y. Utsunomiya, T. Tabata, E. Tsuyuki, and H. Kuyama, Kogyo KagakuZasshi, 1969, 72, 1929.

Author Index

A&eIl, J. W., 126 Abul’Khanov, A. G., 67 Acs, G., 127 Acton, N., 7, 223 Adamska, G., 227 Adamson, G. W., 191,272 Adelman. R. B.. 253 Afanas’ev, Yu. A., 280 Ageeva, A. B., 37, 67, 72 Aguiar, A. M., 2, 20, 65, 254, 255 Aladzheva, I. M., 106, 109 Albers-Schonberg, G., 144 Alberty, R. A., 126 Albrand, J. P., 252, 259 Albrecht. H. P.. 127

Argarwal, K. L., 130 Arima, K., 133 Arison, B. H., 108, 144 Armitage, D. A., 48 Armsen, R., 159 Armstrong, M. C. H., 170 Arnett, E. M., 280 Arnold, E., 153 Arnold. Z., 185 Arshad; A:, 17 Ash, D. K., 230 Astrup, E. E., 48, 220 Atavin. A. S.. 69 Atkinson, M.’ R., 119 Avaeva, S. M., 106 Avery, N. L., 235 Axelrod, E. H., 160 Axen, U., 175

Allison, W, S., 152 Almari, L., 107 Almenningen, A,, 48, 220 Almog, J., 185 Altwerger, L., 127 Alver, E., 118 Alyea, E. C., 269 Akiba, K., 58, 159 Akkerman, V. P., 196 Aksnes, G., 60, 90 Anders, L. R., 279 Andersen, B., 48, 220 Anderson, A. G., 138 Anderson, W. A., 249 Andreeva, L. S., 71, 113 Aneja, R., 149, 150 Anet, F. A. L., 256 Ang, H. G., 47 Angerer, J., 181 Angyal, S. J., 148 Anschiitz, W., 56, 62, 11 1, 201 Antonijevic, V. G., 281 Aoki, Y., 91, 222 Aplin, R. T., 276 Appel, R., 208 Appleton, R. A., 179 Appleyard, G. D., 25 Aquila, H., 146 Arbenz, U., 52 Arbisman, Ya. S., 88 Arbusov, B. A., 37, 38, 77, 101

Babkina, E. I., 262 Backinowsky, L. V., 180 Baddiley, J., 139, 140 Baechler, R. D., 16, 247 Baer, E., 143 Bar, H. P., 135 Bauerlein, E., 146 Bagrov, F. V:, 31 Bailey, A. S., 15, 235, 273 Bailey, J. M., 148 Bakhvalov, G. T., 87 Balaban, A. T., 29 Bald, J. F., 19 Baldeschwieler. J. D.. 279 Baldwin, J. E.,’ 170 ’ Balzer, W. D., 269, 270 Bamburski, E., 227 B a n i d , R., 29 Barabanov, V. I., 96 Baranov, Y. I., 41, 56 Barber, G. A., 140 Bard, J. R., 112 Barili, P. L., 44, 87 Barkley, D. S., 125 Barnett, J. E. G., 149 Barrans. J.. 44 Barrel], ’B. G., 136 Bart, J. C. J., 191,271, 272, 274 Bartell. L. S.. 264 Bartlett, L., 179 Bartlett, P. D., 78, 229 Barton. P. G.. 149 Barton; T. J.,‘223 Bartz, W., 56 Barzilay, I., 149 Bass, W., 153 Basu, H., 143 Battioni, J. P., 59

Abel, E. W., 48, 52 Abramov V. S. 56,57,68, 89

Batliste. M. A.. 24 Bax, P.‘C., 140Bayer, M., 135 Beare. S. D.. 248 Beattie, I. R:, 262 Beattie, T. R., 108, 144 Beauchamp, J. L., 279 Beaudet, R. A., 266 Becke-Goehrine. M.. 49. 191, 196, 197,’ 200,‘ 203; 207, 242, 243 Becker, G., 3, 52, 53, 54 Beg, M., 17 Begum, A., 261 Behrens, N. H., 142 Bellucci, G 44, 87 Belokrinitsl&, M. A., 67 Belovsky, O., 26, 55, 63, 93. 275 Bels’kii, V. E., 103, 113, 280 Belykh, S. I., 215 Benda, H., 4 Benezra, C., 253, 256 Benkovic, S. J., 100, 137 Benschop, H. P., 92,93,97, 152,248 Benziman, M., 138 Bergesen, K., 47 Bergmann, E. D., 43 Berkelhammer, G., 138 Berkowitz, L., 152 Bermann, M., 195, 202 Bernadine, J., 96 Berninger, C. J., 179 Berti, G., 44, 87 Bertrand, M., 179 Bertrand, R. D., 250 Beslier, L., 36, 88, 252 Bestmann, H. J., 159, 161, 166, 169, 175, 177, 181, 245.256 Bezzubova, N. N., 103 Bbacca, N. S., 65 Bhalerao, U. T., 179 Bhanot. 0. S.. 131 Bhatia,’S. B.; 33, 38, 75, 244 Biddlestone, M., 213 Bieber, M., 279 Biellmann, J. F., 138 Biely, P., 140 Biemann, K., 136 Biermnnn, U., 198 Bigg, D. C. H., 258 Bigler, A. J., 33 Bigorgne, M., 266 Binder, H., 105 Bird, C. W., 81, 157

Author Index Birdsall, W. J., 218, 227, 260 B'irum, G. H., 170, 237 B'ishop, Y., 153 Blackburn. G. M.. 95 Blanchard; M. L. L., 245 Blank, M. L., 150 Block, E., 229 Blumbergs, P., 112 Bodkin, C., 90 Boekelheide, V., 84 Bogatyrev, I. L., 114 Bogolyubov, G. M., 278 Bohlmann, F., 177 Boisser, J. R., 121 Bokanov, A. I., 1, 61 Bolden, A. H., 148 Boldeskal, I. E., 266 Bollum, F. J., 133 Bomstein, R., 149 Bond, M. R., 218 Bondinell, W. E., 177 Borden, R. K., 125 Borer, W. Z., 278 Borodin. P. M.. 241 Borowitz, I. J . , ' l l , 12 Bose, A. K., 168 Boter, H. L., 92, 97, 152, 248 Bothner-By, A. A., 253 Botvinik, M. M., 106 Bourn, A,. J. R., 256 Bowers, .M. T., 266 Bowie, J. H., 276 Boyer, J. H., 234 Bracha, P., 153 Bramlett, R. M., 51 Brandt, W. W., 266 Branton, G. R., 217, 269 Brazier, J.-F., 36, 270 Brecht, H., 237 Breebaart-Hansen, J. C. A. E., 112:, 152 Brehame't, L., 130 Breitfeld, B., 66 Brett, D., 12, 50 Brewer. Jr. D.. 179 Briggs,*P. J., 103 Brinckman, F. E., 222,260 Brinigar, W. S., 145 Brion. C.. E., 217 Broesk, F., 113 Brophy, .J. J., 4, 23 Brown. A. D.. 55. 91 Brown:_C:..41.'73.*181,196, _ _ .. 238 Brown, I).H., 49, 85 Brown, T. H., 241 Brownlee, G. G., 136 Brox L. W., 135 Bru& E., 16, 40, 274 Bryson, J. G., 28, 237 Buchanan, J. G., 140 Bucovskii, E. I., 140 Budowsky, E. I., 140 Buchi. H.. 130 Buerger, W., 185 Buina, N. A., 241 Bunton, C. A., 102 Burden, R. S., 185

283 Burdon, J., 62 Burg, A. B., 57, 264 Burgada, R., 34, 35,44, 73, 24 1 Burgos, J., 142 Burk, L. A., 179 Burke, J. J., 280 Burt, D. W., 85, 108 Bushweller, C. H., 238 Byrne, J. R., 53 Cable, J., 217 Cadogan, J. I. G., 56, 77, 23.0, 231, 232, 246 Calhs, C. F., 130 Callot. H. J.. 256 Cameron, TI S., 15, 235, 272, 273, 274 Campbell, D., 69, 109, 238 Cane. D. E.. 68. 186 Caplan, P. J., 259 Cardini, C. E., 140 Cargioli, J., 246 Caries. J.. 14 Carnahan, J. C., 7, 223 Carter, P., 256 Caruthers, M. H., 130 CasDar. M. L.. 201 Casioux, P., 270 Castan, P., 270 Caughlan, C. N., 117,275 Cavill. G. W. K.. 179 Cehovic, G., 125' Cerami, A., 127 Cervinka, O., 55, 93 Chabrier, P., 107, 108 Chadha, J. S., 149, 150 Cha!, H. G., 136 Chalet, L., 144 Chakraverty, K., 138 Chalet, J. M., 180 Chambon. P.. 139 Chan, S., 262, 266 Chan, T. H., 2,46 Chang, B. C., 38, 79, 238 Chang, C. H., 22 Chang, S., 119 Charbonnel, Y., 44 Chavkin. S.. 138 Cheh, G: Y : ,89, 105,, 240 Chen, J. S., 149 Chenault, J., 108 Chenery, D. H., 118,, 129, 374 L I J

Chernov, N. F., 19

, 140 Chittenden, R. A., 262 Chiu, Y. H.. 271 Chivers, T.,'209 Chizhik, V. I., 241 Chladek. S.. 134 Chodkiewicz, W., 59, 88, 248 Chojnowski, J., 266 Chorvat. R. J.. 21 Chremos, G. fi., 66 Christensen, B. G., 108, 144 Christmann, K. F., 164, 165

Churchill, M. R., 220 Cilley, W. A., 69, 109,238 Claeys, E., 1 Clark, R. T., 23, 240 Clark, V. M., 107,137,145, 146,225 Clarke, G. M., 7, 223 Clarke, N., 149 Claydon, M. F., 263 Clemens, D. F., 19, 201 Clifford, K., 154 Cohen, B. M., 88 Cohen, E. A., 252 Cohen, J. S., 95, 127 Cohen, S. S., 134 Cohn, K., 278 Cohn, M., 133, 138 Colowick, S. P., 126 Comb, D. G., 140 Conia, J. M., 181 Cook, A. F., 95, 134 Cook, R. D., 280 Cook, W. H., 126 Cooke, J., 220 Cooke, M., 209 Cooper, A., 232 Cooper, T. A., 145 Cooper, T. G., 138 Coppola, J. C., 118, 129, 275 Corbridge, D. E. C., 261 Corey, E. J., 68, 154, 164, 165, 175, 184, 185, 186, LLY

Corfield, J., 21 Costisella, B., 76 Coulson, A. F. W., 151 Covitz, F., 99, 280 Cowley, A. H., 2,240,244, 248, 250,252 Cox, J. R., 97, 102 Cox. R. H.. 253 Coxon, G. E., 209 Cragg, R. H., 191 CrFger, F., 122, 123, 136,

Crofts, P. C., 42, 87, 262 Crombie, L., 177, 185 Crosbie, K. D., 3, 4, 49, 85,262 Crowder, R. D., 138 Crutchfield, M. M., 130, 236 Cubbon, R. C. P., 227 Cusachs, L. C., 267 Daasch, L. W., 112 Dae-Ki Kang. 57 Dahl, O., 11-' Dalla, C. P., 171 Dalrymple, D. L., 158, 238 Dalton. D. R.. 225 Daly, J. J., 28; 274 Damerau, W., 261 Danielson, R., 246 Daniewski, W. M., 116 Darragh, J. I., 49, 85

Author Index

284 Das, I., 140 Das, K. C., 179 Das, S. K., 211 Das Gupta, A. K., 177 Dashevskii. V. G., 274 Davidson, ’R. S.,‘ 56, 57, 221, 226 Davies. A. P.. 149 Davison. A.. 220 Davydova, L. P., 173 Dawson, G., 279 Dawson. R. M. C.. 149 De Bruin, K. E., 5, 6, 22, 29, 60, 242, 244 Debuch, H., 149 De Clercq, E., 135 Dedek, W., 113 Deiters, R. M., 264 Dejongh, D. C., 279 De Ketelaere, R., 1 Dellinger, E., 19 del Rosario, E. J., 127, 280 Dems, J. M., 181 Demuynck, J., 241 Denkert, M., 142 Denney, D. B., 26, 33, 38, 78, 79, 89, 91, 97, 104, 105, 157, 228, 234, 238, 240, 241, 244, 280 Denney, D. Z., 38, 79, 89, 104, 105, 238, 240, 241 Dennis, E. A., 99, 127, 280 Depasse-Delit, C., 29 Derkatsch. G. I.. 97. 196. 206, 208, 264 De Rudder, J., 121 Desai, V. B., 210, 212 Deverell. C.. 236 Devillers, J.; 106, 258 Dewar, M. J. S., 244 Dheer, S. K., 131 Dianova, E. N., 37. 77 Dierdorf, D. S., 248 Dietsche, W., 152 Di Giovanna. G. V.. 86 Dimroth, K.,’28, 226, 260 Dirheimer, G., 129 Di-Sanseverino, L. R., 275 Di Yorio. J. S.. 265 Dmitriev,‘ B. A:, 180 Doak, G. O., 243 Dodonov, A. M., 281 Doherty, C. F., 177 Dolhun, J. J., 136, 279 Doly, J., 139 Dombrovskii, A. V., 168 Donaldson, G., 119 Dormael, A. V., 269 Dornand; J., 177 Dornauer, H., 161, 177 Doroshenko. V. V.. 97 Douglas, W.‘ M., 209 Downie, I. M., 12, 50 Drahn. K.. 63 Drake,’ J. E., 53 Draper, P. M., 2, 46 Dreeskamp, H., 251, 252 Driver. G. E.. 24 Drozd; G. 1.,’48 Drummond, G. I., 126 I

,

I

Druzhinina, T. N., 140 Dubov, S. S., 38, 88, 265 Duddell, D. A., 262 Duke, J. A., 129 Dungan, C. H., 236 Dunham, L. L., 179 Dunn. G. L.. 177 Durig, J. R.;265 Durneva, A. V., 57 Dwek, R. A., 218,226,259 D’yakonova, N. I., 56, 57, 89 Eastman, D., 13 Ebel, J. P., 129 Ebeling, J., 244 Ebert. H.-D.. 56 Ecker, A,, 222 Eckstein, F., 118, 127, 135, 136 Edel’man, T. G., 189, 201, 205, 206 Edmond, J., 154 Edmundson.,R. S..,67.117. , , 240 Efimova, V. D., 57, 89 Efremov, Y. Y., 114 Efremova, M. V., 113 Egami, F., 133 Egan, W., 23, 28, 247 Egorov, Yu. P., 264, 266 Eguchi, C., 159 Eichenhofer, W., 208 Eisenbert, F., iun.. 148 Elin, E. S., 71- ’ Eliseenkov, V. N., 103, 113 Elix, J. A., 179, 181 Ellenberger, M., 130 Ellzey, S. E., 264 Elser, H., 252 El Sheikh. S. I. A.. 14. 235 Emmick, T. L.. L., 5 5 217 Emsley, J., 217 Engel, M. L., 129 Engel, R. R., 93, 1108 .08 59 Engels, J., 231 Epstein, S. S., 153 Eraut. M. E.. 146 Erikson, R., 90 Ernst, M., 4 Ertel, I., 26, 63, 275 Evdik, M., 196 Evelyn, L., 74 Evstingneeva, R. P., 149 Evtikhov, Zh. L., 32, 36, 77 Eyler, J. R., 279 Ezzell, B. R., 28, 61 Fallis, A. G., 156 FiIrcaSiu, D., 29 Farnham, W. B., 16, 248 Farrell, F. J., 150 Faught. J. B.. 219 Fay& J. P., 267 Feakins, D., 211, 218 Feather, M. S., 148 Fedorova. G. K.. 19 Fennessey, P., 142 Ferekh, J., 36, 270

Fernaiides, J. F., 147 Ferraro, J. R., 263 Feshchenko, N. G., 42, 43, 266 Fields. R., 6, 221, 251 Fife. T. H.. 103. 104 Filatova. I: M.: 194. 206.

Finch; N.; 175 Finer, E. G., 218, 250 Finley, J. H., 91, 97, 104, 234, 241 Fischer, D. E., 26, 81, 254 Fischer, E. H., 153 F?shman, P. H., 148 Fishman, W. H., 140 Fitt, J. J., 175 Flaskerud, G. G., 43 Flemming, J. C., 227 Flesher, J. W., 147 Fletcher. H. G.. iun.. 140

Fogleman, ’W. W., 267 Fokin, A. V., 159 Foltz, E. L., 144 Foucaud, A., 181 Francina, A., 281 Frank, D. S., 99 Frankel, L. S., 246, 259 Fray, G. I., 81 Freed, D., 93 Freedman, L. D., 28, 61 Freeman, R., 249 Freist, W., 122 Friedrichs. B.. 146 Fritz, G., 3, 52, 53, 54 Frayen, P., 60 Frost, D. C., 217, 269 Fuji1 S., 119 FujiAura, S., 139 Fujiwara, T., 118 Fukui. K.. 50 Fukui; T.,’ 124 Fukumoto, K., 232 Fung, B. M., 245 Furber, S. J., 102 Fursenko, I. V., 87 Furuichi, Y., 133 Furukawa, Y., 94, 119 FUSCO, R., 171 Gabrieljan, N. D., 140 Gadreau, C., 184 Gagnaire, D., 246,252,259 Gaidamaka, S. N., 12, 109 Gaines, W. A., 119. Gal, I. J., 281 Galasko, G., 179 Gallagher, M. J., 4, 23, 24, 80 Galle, J. E., 96 Gamaleya, V. F., 196 Gara, A. P., 169, 276

285

Author Index Garcia Trejo, A., 140 Gardner, P. J., 47 Garming, A., 7 Garner, G. V., 232 Garner, R., 232 Garratt, P. J., 183 Gavrilova, G. M., 69 Gay, D. C., 100 Gazizov, M. B., 73 Gazizov, T. Kh., 89, 113 Gelting, N. C., 11 Genkina, G., 206 Gent, P. A., 149 Germa, H., 34, 35, 241 GCro, S. D., 149 Ghauviere, G., 23 Gibas, J., 20, 179 Gick, W., 42, 199 Gielen, M., 29 Giere, H. H., 194, 197 Gigg, R., 149 Gilardi, R., 274 Gilje, J. 'W., 44 Gillilan, W., 152 Gillis, R. G., 277 Gilyarov, V. A., 206 Gindl, H., 135 Ginsberg, V. A., 38 Ginsburg, V., 140 Girota, N. N., 108 Glaser, S . L., 33 Glemser, O., 198, 216, 237 Glidewell. C., 3, 262 Goddard,' N.; 53 Godefroy, T., 133 Goetz, H., 171, 206, 268, 269 Goggin, P. L., 262 Gokhale, A. M., 179 Goldwhite, H., 243, 262, 266 Golen, J. A., 264 Gonnet, M. C., 81, 281 Goodacre, G. W., 271, 272 Goodchild, J., 131 Goodfellow, R. J., 262 Gorbatenko, Zh. K., 42 Gordon, M., 66 Gordy, W., 222 Gorelenko, S. V., 41, 56 Gorenstein, D., 29, 244 Gotsmanni, G., 195 Gottlieb, (3. R., 155 Gottschalk, E. M., 133 Goya, A. E., 44 Gozman, .[I P., 33 Grams, G. W., 122 Grangette, H., 96 Granoth, I., 43, 47, 235 Grant, C. T., 154 Gras, J. L., 179 Graves, D. G., 153 Grechkin, E. F., 19, 50, 51, 52 Grechkin, N. P., 241 Gredig, R., 238 Green, B., 177, 209, 212 Green, J. 13. S., 48, 262 Green, M., 184, 251

Green. P. J.. 241 Greengard, P., 126 Crib, A. V., 19 Griffin, B. E., 131 Griffin, C. E., 66, 116, 262 Griffith, D. L., 103, 137 Gnffith, 0. H., 153 Grigor'eva, I. K., 40 Grim, S. O., 241, 251 Grimm. L. F., 192. 202 Grisebach, H.; 140 Grishin, N. N., 278 Grishina, 0. N., 113 Grobe, J., 262 Gross, H., 76, 185 Grosse-Bowing, W., 192, 197 Grunberg-Manago, M., 133 Grutzmacher, H. F., 276 Guibe-Jampel, E., 96 Gulati, A. S., 38, 75, 244 Gundermann,, K. D., 7 Gunn. P. A., 179 Gupta, K., 102 Gupta, N., 130 Gupta, S. K., 181 Gur'yanova, I. V., 34, 57, 89 Gusera, I. S., 110 Guseva, T. A., 96 Gutmann, V., 61 Gutowsky, H. S., 249 Gymer, G. E., 81 Haag, A,, 56 Haase, L., 76 Habarowa, M. I., 1313 Hackley, B. E., jun., 152 Hackley, E. B., 152 Hagele, G., 42 Haemers, M., 259 Hafner-Roll. E.. 191 H ahn, W. E:, 72, 185 H ajdu, J., 149 H alasa, A. F., 217 H all, C. D., 225 H all, L. D., 74 H all, R. E., 6 H almann, M., 95, 146 H alpern, A., 104 H ameed, A., 47 H amer, N. K., 100 H ammes, G. G., 127, 280 H ampton, A., 135 H ands, A. R., 276 H anessian, S., 279 H ansbury, E., 128 H antz, A., 107 H anze, A. R., 122 H arada, F., 127 H arman, J. S., 49 H armon, R. E., 148, 181 H arqp, D. N., 2,33,46,230 H arris, J. J., 49 H arris, M. R., 127 H arris, R. K., 218, 250 H artman, F. C., 151 H artzler, H. D., 86 H asegawa, S., 139

Hjaslinger, E., 189 H,assid, W. Z., 139 H assner. A.. 96 H aszeldine, 'R. N., 6, 221 H ata, T., 96 H aubold, W., 49, 196 H awes. W.. 61 H ayaishi, O., 126 H ayatsu, H., 133, 136 H ayes, F. N., 128 H eake, P., 280 H ebig, R., 122 H echenbleikner, I., 2 H eckman, G., 194 H eeres, G. J., 183 H eine, H. W., 171 H eller, C. I., 235 Hellwinkel, D., 27, 31, 237, 270, 277 Hellyer, J. M., 102 H emming, F. W., 142 H endlin. D.. 144 Hendrickson, D. N., 218 Henglein, A., 225 Hengstberger, H., 156 Hennion, G. F., 86 Henson, P. D., 62 Hepnerova, M., 55, 93 Herald, C. L., 184 Hernandez, S., 144 Herriott. A. W.. 248 Hesz, A:, 218 ' Hettche, A., 28, 226, 260 Hettler. H.. 122 Hewertson.' W., 10 Hewlett, C:, 227 Higashi, Y., 142 Hiehsmith. R. E.. 53 Hignite, C : , 136 ' Hilderbrand, J., 265 Hilderson, H. J., 279 Hill, D. L., 154, 264 Hnoosh. M. H.. 260

Holm; R.'H., 269 Holman, M. J., 134 Holmes, R. R., 264 Holtschneider, G., 197 Holtz, D., 279 Hol9, A., 95, 120, 124 Honaker, C. B., 136 Honjo, M., 94, 119 Hoos, W. R., 31 Hori. T.. 143 Horhuth, P. B., 196, 238 Horn, D.. E., 181 Horn, H...G.. 203 Horner, L., 4, 26, 63, 65, 227, 229, 270, 275 Horning, D. P., 101 Horrocks, W. De W., 269 Horton, A. D., 136 ~

I

Author Index Horton, H., 105 Horvath, G., 218 Hosokawa, Y., 142 Hovanec, J. W., 112 Howgate, P., 181 Hribar, J. D., 279 Hsia, J. C., 153 Huber. W.. 175 Hudson, A., 226 Hughes, A. N., 10, 28, 156 Hughes, C. T., 179 Hughes, R. G., 153 Huisgen, R., 16, 40, 238, 274 Hunt, D. F., 136 Hussain, H. A., 226 Hutchinson, D. W., 107, 119, 145, 146, 225 Hutton, J., 185 Ichimura, K., 50 Ide, H., 140 . Ignat'ev, V. M., 88 Ikehara. M.. 124. 127, 132 . Iketa, S:, 242 Illingworth, S. H., 52 Imai, K., 94, 119 Imai. T.. 138 Imhof, J., 61 Inamoto, N., 58, 159 Inokawa. S.. 222 Inoue, S.', 177 Inouye, Y . , 34, 84 Inukai, K., 70, 222 Iogansen. A. V.. 266 Io&. B . ' L 88, -240 Irani,' R. R;, 130 Irelan, J. R. S., 2, 20, 65, 254, 255 Irie. S.. 133 Irving,'K. C., 171 Isaacs, N. W., 118, 129, 275 Ismagilov, E. K., 12 Ismail, R. M., 78 Isosenkova, L. A., 118 Issleib, K., 3, 17, 73, 163 Italinskaya, T. L., 258 Ito, T., 242 Itsaka, O., 143 Ivanik, V. I., 51 Ivanov, B. E., 37, 67, 72 Ivanova, Sh. M., 264 Ivashchenko, Y. N., 196 Ivasyvak, N. V., 113 Iverson, P. A., 156 Ivin, S. Z., 48, 88 Iwacha, D., 123 Izosenkova, L. A., 66 '

Jackel, G., 222 Jackson, G. F., 16, 247 Jackson, M., 144 Jackson, W. R., 244 Jacobson, R. A., 272 Jacques, M. St., 246 Jafry, S. W. S., 10, 156 Jakobsen, H. J., 246, 255, 256 Jameson, C. C., 249

Jamieson, G. W., 104 Janion. C.. 133 Jannseh, hi. J., 183 Jansen, W. M., 199 Jardetzky, O., 127, 144 Jastorff, B., 122 Jeanloz, R. W., 140 Jeck, R., 138 Jefferson, R., 47 Jenkins, I. D., 80 Jenkins, J. M., 250 Jenkins, M. E., 158, 238 Jennings, W. B., 244 Jensen. D.. 281 Jensen; E. 'H., 230 Jensen, K. A., 230 John, J. P., 2, 20, 255 Johnson. K. L.. 133 Jolly, W: L., 218 Jonassen, H. B., 267 Jones, A., 251 Jones, A. S., 181 Jones. D. H.. 33. 78, 228. 244 Jones, E. R. H., 156 Jones, G. H., 125, 127 Jones, R. A., 25 Jones, R. A. Y., 112 Juds, H., 206 Jugelt, W., 63, 227 Jurie. G.. 240 Jung,' D.,' 207 Jung, M. J., 138 Junkes, P., 56 Jurgeleit, W., 229 I

,

,

I

Kabachnik, M. I., 66, 118, 206, 266 Kaboshina, L. N., 173 Kahan. F. M.. 144 Kainosho. M.,' 89, 1 17, 136 258 Kalabin, G. A., 69 Kalabina. A. V.. 50 Kalibabchuk, N: N., 225 Kalinina, G. R., 51 Kalir,.A., 43, 47, 235 Kamai, G. K., 12, 45 Kametani, T., 232 Kang, D. K., 264 Kaplan, M. L., 78, 229 Kapoor, P. N., 3 Kapur, J. C., 177 Karain. Yu. M.. 71 Karre, I., 274 ' Karlsson, K. A., 143, 279 Karpova, E. N., 1 KasDarek. F.. 111 Kasiuri, G., 102 Kasturi, K. R., 102 Kataev, E. G., 8 Kato, K., 94, 120 Kato, T., 94, 119 Katritzky, A. R., 112, 117, 257 Katz, T. J., 7, 223 Kaufman, B. L., 67 Kaufmann, G., 265 Keat, K., 218 Keijer, J. H., 152 ~

~~

Keiter, R. L., 241, 251 Kemp, R. H., 66 Kennard, O., 118, 129,275 Kenyon, G. L., 112, 129 Kerr, K. A., 118, 129, 275 Kerr, V. N., 128 Kessel, A. Y., 61 Kessler. A.. 6 Kessler: H.: 244 Keyzer,. H.,. 262 Khaikin, L. S., 258, 267 Khairullin, V. K., 46, 114 Khan. S. A.. 101 Khardin, A.'P., 47 Khorana, H. G., 126, 130, 131, 143, 147 Khurana, C. K., 177 Khusainova, N. G., 86,109 Kilcast, D., 227, 260 Kimbrough, R. D., 51 Kimura, J., 94, 120 King, C. S., 25 Kina. L.. 138 King; R.' B., 3 King, S. T., 263 Kirby, A. J., 101, 118, 129, 137, 275 Kirby, K. C., 12 Kireev, V. V., 191, 206, 215, 217 Kirilov. M.. 187 Kirk, M. C : , 154, 264 Kirman, J., 6, 221 Kirsanov, A. V., 19, 42, 43, 109, 187, 203 Kisilento, A. A., 206 Kitazume, S., 242 Kjellstrom, W. A., 150 Kjrage, H. M., 118 Klabuhn, B., 171,206,268, 269 Klapper, H., 112, 246 Kleiner, H.-J., 232 Kleppe, K., 130 Kluger, R., 99, 280 Klusmann, P., 199 Klyashchitskii. B. A., 148, 149 Klyne, W., 179 Knaff, D. B., 145 Knaggs, J. A., 150 Knoth, W. H., 242 Knowles, J. R., 151 Kobata, A., 140 Kobavashi. E.. 216 Kobayashi; T.; 8 Koch, H., 113 Koch. R. W.. 217 Kochetkov. N. K.,~.140, 180Kochi, J. K., 226 Kochkol'da, S . P., 56 Koelliker, U., 175 Koeppl, G. W., 247 Koh, L., 83 Kohler, J. J., 218 Koike. T.. 133 Koizumi, T., 280 Kokoszka, Ci. F., 222, 260 Kolaleva, T. V., 43

Author Index Kolesnikov, G. S., 191, 206, 2 15, 217 Kollmar, H., 239 Kolomeets, A. F., 159 Kolotilo, M. V., 208 Komarov, N. V., 19 Komissarova, S. L., 8 Komlev, I. V., 140 Kondrat’ev, Yu. A., 88 Kondrateva, R. M., 46 Kongpricha, S., 197 Kopay, C . M., 158 Kornberg, A., 147 Korolev, B. A., 61 Kosman, D. J., 153 Kosolapoff, G. M., 55, 91 Kost, D., 253, Kostyanousktt, R. G., 3 Kotova, Y. G., 106 Kovalev, L. S., 77 Kovaleva, T. V., 42 Kovetskii, Yu. M., 266 Kowollik, G., 124 Kozlov, E. S., 12, 109 Kozlov, N. S., 71 Kraay, G. W., 93 Krapcho, A. P., 181 Krause, L,., 275 Krawieki, C., 112 Krebs, E. G., 153 Krech, F., 3, 17, 275 Kresky, H. W., 98 Krishnamurthy, G. S., 247 Kropacheva, A. A., 196 Krueger, .P. M., 279 Kruglikova, R. I., 51 Krupnov, V. K., 88, 109 Krusic. P. J.. 226 Krutskii, L. N., 45 Kuchen, W., 42 Kuehl, F. A., jun., 108, 144 Kugel, R. L., 214 Kukhar, V. P., 200 Kulik. S.. 231. 232 Kulikowski, T., 122 Kumamoto, K., 222 Kumar, A., 130 Kumashiro, I., 119 Kummer, D., 3, 52 Kurland, R. J., 154 Kusama, T., 133 Kusov, Yu. Yu., 140 Kustanovich, I. M., 173 Kuyama, H., 281 Kuznetsov, E. V., 8 Kuznetsova, L. D., 159 Kynaston, W., 48, 262 Kyogoku, Y., 136 L’Abbe, G., 171 Labarre, J. F., 270 Labarre, M. C., 270 Laing, D. C., 179 Lakatos, B., 218 LaMar, G. N., 242 Lambert, J. B., 16, 247 Lambeth, D. O., 146 Lambeth, P. F., 221 Lamotte, k., 18, 281

287 Lampin, J. P., 73 Landau, M. A., 48, 265 Latipher, E. J., 2 Lapidot, Y., 149 Lardy, H. A,, 146 Larkin, J., 155 Larsen, O., 11 Larson, A. C., 118,129,275 Larsson, L., 152 Laskowski, M., 133 Lassmann, G., 261 Last, W. A., 211 Latscha, H. P., 196, 200, 238, 242 Lauff, J. J., 71 Laurent, J. P., 240 Lavielle, G., 185 Law, J. H., 143 Lawson. A. M.. 279 Leanza,’W., 108, 144 Lee, J. B., 12, 50 Lee, J. D., 271, 272 Lefebvre. M. G.. 183 Lehn, J. ’M., 247 Le-Hong, N., 180 Lehr, W., 211, 213 Leigh, G. J., 269 Leloir, L. F., 140, 142 Le Maitre, D., 107 Lennartz, W. J., 142 Lepine, P., 121 Le Roux, Y., 96 Letcher, J. H., 236 Letsinger, R. L., 55, 122 Levas, E., 167 Levin, I. S., 263 Levy, D., 11, 17, 235 Lewis, C. J., 216 Lewis, R. A., 22, 55, 269 Lieber, K., 227 Leibman, S. A., 225 Leidhegener, A., 56 Liehr, J. G., 157, 158, 238 Lienert, J., 166 Lieske, C. N., 112 Lindner. E.. 56 Liotta, h., 93, 108 Lipkin, D., 126 Lipscomb, W. N., 271 Lischewski. M.. 163 List, G., 152 ‘ Litovchenko, N. R., 200 Lobanov. D. I.. 66. 118 Loginova, E. I.; 37; 72 Lohrmann, R., 133, 146 Lohs, K. L., 261 Long, G. J., 277 Lord, E., 12 Loutellier, A., 266 Lowrie. G. B. .tert.. 171 Luchen, E. A. C., 261 Luff, B. B., 218 Lugovkin, B. P., 71 Lund, H., 156 Lustig, M., 48, 209 Luttrell, B. M., 148 L’Vova, F. P., 110 Lawler. J. M.. 101. 104 Lybyec M. J.; 148’ Lynden-Bell, R. M., 250

McCarthy, J. R., jun., 134 McCloskey, J. A., 279 McCormick, D. B., 124 McCrindle, R., 179 MacDiarmid, A. G., 19 McDowell, C. A., 269 McFarlane, W., 239, 249, ?
&.I&

Mack, D. P., 217 Mackie, R. K., 230, 246 McLain. A. R.. 6 McLean, R. A: N., 44 McMurray, C. H., 152 McNeilly, S. T., 73 McTigue, P. T., 103 Miirkl, G., 26, 27, 28, 63, 81, 167,223, 254,274 Mageswaran, S., 155 Magnuson, J. A,, 154 Magnuson, N. S., 154 Mahler, W., 242 Maier, L., 48, 112, 129,238 Majoral, J. P., 257 Makhamatkhanov, M. M., 66 Malevanndya, R. A., 66 Maley, F., 140 Malisch, W., 163, 252 Mallams, A. K., 179 Malone, B., 150 Manatt, S. L., 252 Mandel, P., 139 Manhas, M. S., 168 Manley, T. R., 217 Marcus, I., 125 Mardersteig, H. G., 189, 198 Marecek, J. F., 103, 137 Marioni, F., 44, 87 Mark, V., 236 Markgraf, J. H., 235 Markham, R., 126 Marmor, R. S., 57, 111, 201, 227 Marshall, J. A., 179 Marsi, K. L., 23, 38, 79, 238, .240 Marsili, A., 44, 87 Martin, M. G. J., 245 Martz, M. D., 16, 59, 235 Mason, G. W., 263 Mason, R. F., 7 Mason, S. F., 270 Masse, J., 103 Massey-Westropp, R. A., 169, 276 Mastennikov, V. P., 107 Mastryukova, T. A., 66, 266 Masuda, T., 94, 119 Mata, J. M., 144 Mathey, F., 51, 63 Mathey, M. F., 28 Mathiaparanam, P., 33 Matough, M. F. S., 12, 50 Matschiner, H., 275 Matseuda, R., 17 Matsubara, H., 139

Author Index

288 Matsui, M., 179 Matthews, C. N., 170, 237 Matthews, R., 186 Matveeva, L. M., 116 Matyusha, A. G., 208 Matzura, H., 18, 228 Mauret, P., 267 Maurin, R., 179 Mazeline, C., 261 Mazhar-ul-Haclue. -~ 66, 117, ~

271,275

Meadows, D. H., 127 Meek. D. W.. 269 Meek; J. S., 83 Meinel, L., 189, 190, 198, 205

,

Meissner, L., 138 Melligen, K., 90 Melnichuk, E. A., 42 Mel’nikov, N. N., 114, 258

Mendenhall. G . D.. 78, ,~

229

Meppelder, F. H., 92, 93, 97, 248

Mercer. A. J. H.. 276 Mercier, D., 149’ Merigan, T. C., 135 Merlin, J. C., 281 Meyers, J. A., 71 Mhala, M. M., 102 Michalski, J., 84, 97, 98,

104, 112, 115, 117, 234, 257 Michel, H. O., 152 Michel, N., 106 Michelson. A. M.. 133 Michniewiez, J., 13 1 Micolajczyk, M., 90, 97, 104, 115, 118, 240

Mikhailyuchenka, N. K., 97

Mildavan, A. S., 138 Miller, A. K., 144 Miller, D. J., 267 Miller. G. R.. 251 Miller; J. A.,’58, 73, 82 Miller, J. M., 276 Miller. S. 1.. 247 Miller: T. W., 144 Mills, J. L., 2, 240 Milne, G. M., 160 Milstein, S., 104 Mingos, D. M. P., 269 Mislow, K., 5, 6, 16,22,23,

28, 29, 55, 60, 62, 242, 244, 247, 248, 269

Mitchell, E. W., 67, 117, 240

Mitchell, H. L., 48, 242 Mitchell, K. A. R. ,217 Mitchell, P., 145 Mitchener, J. P., 2 Mitsunoba, O., 94, 120 Mlotkowska, B., 97 Moats, W. L., 117, 275 Mochales, S., 144 Moeller, T., 219 Moffatt, J. G., 125, 127, 143

Mollev, U., 262 M olyavko, L. I., 97 Mondt, J. L., 84 M oran, E. F., 208 M oreland, C. G., 28, 237 M o n , K., 179 M orita, K., 8 M oritani, I., 168 M orris, E. D.. 271 M:orris; F., 140 M;orrow, C. J., 2, 20, 255 Miorton. R. A.. 142 Mrose, W. P., 17’9 M[oskalevskaya, L. S., 19 M[oskova, V. V., 110 M[otherwell. W. D. S.. 118. 129, 275

I

’

Motygullin, G . Z., 113,280 Mousseron-Canet, M ., 177 Muelder, W. W., 265 Mueller. D. C.. 16. 247 Muetteities, E.‘ L.,’ 242 Mui, P. T. K., 138 Mukaiyama, T., 17, 96 Muller, A., 265 Munoz, A., 36, 270 Munsch, B., 247 Muntz, R. L., 248 Murakami, Y . , 103, 104 Muramatsu, H., 70, 222 Murao, K., 127, 132 Murayama, W., 275 Muroi, M., 34, 84 Murphy, A. J., 129 Murray, A. W., 119, 146 Murray, M., 41, 73, 196, 238

Murray, R. W., 78, 229 Mushika, Y., 96 Musina, A. A., 61, 77 Muylle, E., 1 Myers, T. C., 147 Nabi, S. N., 211, 218 Nagao, Y . , 222 Nagase, O., 142 Nagashima, N., 275 Nagyvary, J., 123, 134 Nakahara, Y., 179 Nakamoto, K., 263 Nakamura, A., 89, 117, 258

Nakamura, K., 147 Nakamura, S., 183 Nakayama, J., 236, 261 Narang, S. A., 131 Narasimhan, N. S., 179 Narech, J., 106 Nash, J. A,, 252 Nasielski. J.. 29 Naumann, K.,5, 6, 22, 29, 60, 62, 242

Naumov, V. A., 274 Navech. J.. 257. 258 Negrebetskii, V. V., 210, 258

Neil, G. R., 226 Neilson, T., 132 Nelson, A. J., 223

Nelson, K. W., 86 Nelson, W., 222 Nesbit, M. R., 117, 257 Nesterov, L. V., 61 Neumann, H., 65,227 Newmark, R. A., 250 Newton, M. G., 102 Nguyen Thanh-Thuong, 107

Nichols, D. I., 239 Nichols, G. M., 207 Nicholson. D. A.., 69,, 109. ~

238

Niecke, E., 192, 216 Nielson, J. A. A., 246, 255 Nifant’ev. E. E., 87. 116 Nikolaev,? A. V.‘, 280 Nikolotova, Z. I., 241 Nishida, S., 168 Nishimura, S., 127 Nitta, T., 107 Nixon, J. F., 47, 243, 250 Noce,’P., 138 . . Noth, H., 189, 190, 198, 205

Nofre, C., 96 Nonhebel, D. C., 155 Noosh, M. H. H., 227 Nordman, C. E., 271 Norman, A. D., 52 Norton, M. G., 262 Noyori, R., 175 Nuretdinov, I. A., 241 Nuretdinova, 0. N., 101 Nurtdinov, S. K., 45 Nussbaum, A. L., 134 Nuzhdina, Yu. A., 264 Nyquist, R. A., 265 Nyu, K., 232 Obata, N., 158 Oboz’nikova, E. A., 173 O’Brien. R. D.. 153 O’Bryan, J. M.; 138 O’Connell, E. L., 138, 151 Offord. R. E.. 151 Ogasawara, K.,232 Ogata, T., 222 Ogata, Y . , 56, 115, 223, 254

Ogilvie, F. B., 250 Ogilvie, K. K., 123 Ohno. M.. 34. 84 Ohse,’H., ‘13 ‘ Ohtsuka, E., 130, 132 Ojima, I., 58 Okada, I., 50 Okada, S., 142 Okamoto, Y . , 107 Okon, K., 227 Okuda, S., 138 O’Laughlin, J. W., 281 Olbrich, H., 26, 81, 254 OlivC, J.-L., 177 Ollis, W. D., 155 Olthof, R., 219 Omelanczuk, J., 115 O’Neil, J. W., 238 Opar, G . E., 124

289

Author Index Oppenheimer, A. W., 81 Orgel, L. E., 95, 133, 146 Orlov, W. F., 67 Ormond, R. E., 108, 144 Ortiz de Montellano, P. R., 154 Osadchenko, M., 59 Osanova, N. A., 40 Osipenko, N. G., 66 Ossip, P. S., 280 Ota, S., 177 Ott, D. G., 128 Ozin, G. A., 262 Paddock, N. L., 207, 209, 217, 218, 226, 259 Padwa, A., 13 Paetsch, J. D. H., 116 Pailer, M., 189 Painter, T. M., 47 Pak, V. D., 71 Paligoric, I., 281 Pampalone, T. R., 183 Pande, K. C., 13, 85 Pankau, M., 152 Pant, B. C., 264 Para, M., 118 Paradkar, M. V., 179 Parker, D. J., 152 Parker, D. M., 42, 87, 262 Parshall. G. W.. 242 Parshina, V. A.; 60 Partos, R. D., 26, 173 Pashinkin, A. P., 89, 113 Pasmanyuk, S. V., 37, 72 Patchett. A. A.. 108. 144 Patin, H'., 65 Pattenden, G., 177, 179 Patwardhan. M. D.. 102 ' Paul, I. C., 219 Pavanaram, S. K., 143 Pavlenko, A. F., 196 Peach, J. M., 15, 235, 273 Peake, S. C., 49, 272 Pelah, Z., 43, 47, 235 Pelavin, M., 218 Peluso, R., 201 Pennock, J. F., 142 Pentcher, P. G., 148 Perevezentseva, S. P., 34 Perret, F., 180 Perry, G. M., 62 Petersen, L. K., 44 Petrov, A. A., 31, 32, 36, 37, 77, 88, 240, 278 Petrov. K. A.. 60 Petrova, G. M.,60 Petrova, J., 187 Pettit. G. R.. 177. 184 Pfanrierer, F., 3 ' Pfohl, S., 169 Phillips, B. E., 126 Phillips, D. R., 103 Pierson, G. O., 229 Pietschmann, J., 212, 213 Piette. L. H.. 153 Pignolet, L. H., 269 Pike, J. E., 175 Pilgram, K., 13 Pilot, J. F., 33, 38, 75 ~~

Pimenova, V. V., 149 Pinchuk, A. M., 196 Pirkle, W. H., 248 Pitina, M. R., 210 Place, B. D., 143 Platenburg, D. H. J. M., 92, 97, 248 Plattner, J. J., 179 Pochan, J. M., 267 Pochon, F., 133 Podder. S. K.. 133 Pogson; C. I.,- 152 Poh, P., 157, 221, 264 Poindexter, E. H., 218, 226, 259 Pokhodenko, V. D., 225 Polenov, V. A., 181 Polezhaeva. N. A.. 38 Pongs, O., 132 ' Ponnamperuma, C., 119 Popilin, V. P., 206 PopjBk, G., 154 Posternak, T., 125 Potenza, J. A., 218, 226, 259 Powell, R. L., 225 Prejean, G. W., 2, 20, 255 Preobrazhenskaya, N. N., 136 Preobrazhenskii, N. A., 149 Priebe, E., 73 Prikoszovich, W., 118, 239 Prince, R. H., 17 Pritchard, J. G., 278 Privat de Garilhe. M.. 121 Prout, C. K., 15,235,'272, 273, 274 Provenzale, R. G., 123 Pudovik, A. N., 34, 46, 57, 71, 86, 88, 89, 103, 106, 109, 113 Pudovik, M. A., 71 Pullen, K. E., 43 Quarles, R. H., 149 Quin, L. D., 16, 17, 28, 59, 235. 237 Quirk; R. P., 280 Rabinowitz, J., 119 Radford, T., 279 Raevskaya, 0. E., 89 Raigorodskii, I. M., 191, 217 Rajbhandary, U. L., 130 Rake, A. T., 276 Ramer, R. M., 168 Ramirez, F., 33, 38,75,244 Rammler. D. H.. 140 Randall, E. W., 246 Ranganathan, S., 80 Rao, K. V. J., 143 Rapoport, H., 177, 179 Rasberger, M., 156 Rassadin, B. V., 266 Ratts, K. W., 26, 173 Rauk, A.. 247 Raulet, C., 167 Rawlinson, D. J., 47, 228

Rav. S. K.. 211 Rakmov, A. I., 73 Razumova, N. A., 31, 32, 36, 37, 77 Razuvaev, G. A., 40 Redmore. D., 70, 185 Reese, C.' B.,'131 Regitz, M., 56, 62, 111, 201, 227 Reich, E., 127 Reider, D. P., 208 Reiff, H. F., 264 Reilly, C. A., 249 Reinhold, D. F., 119 Remy, P., 129 Renowden, P. V., 103 Revel, M., 129 Reynolds, G. D., 169 Richards, E. M., 255 Richards, G. M., 133 Richards, R. E., 218 Riddle, C., 53 Rllling, .H. C., 154, Riva di Sansever~no, L., 118, 129 Robbins, P. W., 142 Robert. J. B.. 259 Roberts, G. C. K., 127 Roberts, R. J., 155 Rob!ns, M. J., 134 Robins, R. K., 134 Robinson, L., 102 Roe. J.. 134 Roedig: A., 167 Rosch, L., 53 Roesky H. W., 41,48,192, 194. i97. 200, 202, 203, . 216' Rohmer, R., 265 Romanov. G. V.. 89 Romanova, G. N.,61 Rosario, M. D., 44 Rose, I. A., 138, 151 Rose, S. H., 217 Roseman, S., 140 Rosenstein, R. W., 154 Rosenthal, D., 201 Ross, D. S., 49, 85 Rossknecht. H.. 92, 200, 242 Rostock, K., 161, 177 Roth, G. C., 130 Rottman, F.. 133 Roussel, J., 36, 252 Rozen, A. M., 241 Rozhkov, I. N., 62 Rozinov. V. G., 19, 50, 51, 52 Ruden, R. A., 179 Rudner, B., 49 Rudolpli, R. W., 250 Rudolph, S. A., 126 Ruff, J. K., 209 Runquist, 0. A., 229 Ruprecht, H. D., 26, 63, 275 Rusek, P. E., 11, 12 Russ, C. R., 53 Russell, A. F., 148 Rutherford, D., 148 '

I

_

_

Author Index Ryl'Tsev, E. V., 266 Ryschkewitsch, G. E., 240 Saalfrank, R. W., 175, 256 Sabon, F., 103 Sadamori, H., 104 Saenger, W., 118, 127 Safe, S., 15, 230 Sagatys, D. S., 247 Saikachi, H., 170, 183 Saito, M., 133 Saito, T., 119 Sakurai, H., 91, 107, 115, 222, 224, 261 Salikhov, S. G., 37, 72 Salo, W. L., 140 Samejima, K., 143 Samitov, Yu. Yu., 37, 38, 61 Samokhvalov, G. I., 173 Sancher, R. A., 95 Sanchez, M., 34, 36, 88, 252 Sanchez, R. A., 146 Sandermann, H., jun., 140 Sandul, G. V., 225 Saneyoshi, M., 121 Sanger, F., 136 Santo, T., 93 Sargent, M. V., 181 Sarma, G. R., 143 Satchell, D. P. N., 103 Sato, K., 177 Sauer, J., 231 Savariault, J. M., 270 Savignac, P., 108 Savintseva, R. N., 68 Sawada, F., 121 Sawodny, V. W., 265 Sazonov, N. V., 196 Schaaf, T. K., 175 Schaller, H., 167 Scheffler, M., 225 Scheit, K. H., 133 Schenk, W., 27, 237 Scher, M., 142 Scherer, H., 62, I1 1 Scherer, 0. J., 42, 199 Schiebel, H. M., 118, 240 Schiemenz, G. P., 1, 268 Schindlbauer, H., 118, 239 Schindler, N., 211, 215 Schlimme, E., 136 Schlosser, M., 164, 165 Schlueter, A. W., 272 Schmidbaur, H., 163, 204, 252. Schmidpeter, A., 92, 191, 200, 211, 215, 237, 242, 244. Schmidt, D., 63, 227 Schmidt, H. L., 146 Schmidt, U., 222, 276 Schmitt, K. D., 14, 47, 80, 97. 228 Schmutzler, R., 41, 47, 48, 49, 73, 196, 238, 242, 243, 250, 251, 272 Schneider, W. P., 164

Schneider-Bernloehr, H., 133 Schonberg, A., 187 Schray, K. J., 100, 137 Schubert, H., 27, 63, 223 Schulze. H.. 265 Schumann, 'C., 251 Schumann, H., 4, 52, 53, 237 Schunn, R. A., 242 Schwartz, A., 119 Schwartz, A. W., 95, 119 Schwarz, W., 280 Schwarzmann, M., 194 Schweizer, E. E., 25, 157, 158, 179, 238 Schwind, H., 203 Scott, P. H., 230 Searle, H. T., 207 Sears, D. J., 56, 77, 230, 23 1 Sedelnikowa, E. A., 133 Segal, R., 138 Sellers, H., 157, 221, 264 Seltzer, S., 26, 157, 280 Selvarajan, R., 234 Sen Gupta, K. K., 47 Sepulveda, L., 102 Sergeeva, V. P., 107 Sevin, A., 59, 88, 248 Sevden-Penile. J.. 183 Seiferth, D., 57,'111, 116, 201, 227 Sgaramella, V., 130 Shabarova. Z. A.. 136 Shaffer, E.'T., 179 Shagidullin, R. R., 37, 45, 72 Shahak, I., 185 Sharp, D. W. A., 49, 85 Shaturskii, Ya. P., 19 Shaw, D., 246 Shaw, M. A,, 8,9,156,245 Shaw. R. A.. 210.211.212. 213, 218 Shechter, H., 227 Sheldon. R. A.. 56. 57 Sheldrick, G. M.,3, 4, 262 Sheluchenko, V. V., 48, 206, 238 Sheppard, N., 263 Sherman, E. O., 242 Sherman, W. R., 148, 279 Shermergorn, I. M., 113 K. Shetsova-Shilovskava. . . * D., 114 Shevchenko, V. I., 196, I

200

,

,

Shevchuk, M. I., 168 Shibaev, V. N., 140 Shima, K., 222 Shima, T.. 139 Shimiza, Y., 275 Shimizu, M., 142 Shokol, V. A,, 97, 196,206, 264 Shostenko, A. G., 281 Shreeve, J. M., 43 Shtepanek, A. S., 187, 203 Shugar, D., 122, 133

Shulman, J. I., 164, 165, 184 Shushmor, V. A.. 107 Shutt, J. R., 21 Shvets, V. I., 148, 149 Shvetsov-Shilovskii, N. I. , 210, 258 Siddall, J. B., 179 Siddiqui, M. S., 17 Sie. H. G.. 140 Silhau, W , 276 Simonov, A. P., 194 Simpson, P., 85, 90, 108 Simuth. J.. 133 Singer, 'E.,' 187 Singh, B. B., 80 Sisler, H. H., 44, 53, 241 Sklvankina. V. A.. 106 Skr-owronska, A.,' 84, 98, 234 Skuballa, W., 177 Slawisch, A., 212 Slowinskii, Yu. L., 205 Smets, G., 171 Smirnov, A. N., 47 Smith, B. C., 14, 210, 211, 212. 235 Smith; C. P., 33, 38, 75, 230, 244 Smith, D. M., 56, 77, 230, 23 1 Smith, H. O., 239 Smith, J. D., 88, 143 Smith, J. G., 262 Smith. M.. 126. 132 Smith; N.,' 125 ' Smrt, J., 133 Snyder, C. D., 177 Snyder, E. I., 12, 50, 233, 74 1

Snidir, F., 150 Snyder, J. P., 245 Sobchuk. T. I.. 46 Sobeir, M.E.,'14, 235 Sochazcka, R., 104 Soffer, M. D., 179 Sokal'skii, M. A,, 48 Sokolov, S. D., 148, 149 Solol'skaya, G. N., 51 Somers, J. H., 17 Sorm. F.. 120 Sosnovsky, G., 14, 47, 80, 97 107, 228 Sowdrby, D. B., 209, 212 Spain, V. L., 179 Spangenberg, S. F., 44,241 Spence, R. A., 117, 153 Soirina. L. V.. 71 Spiro, T. G., 150 Spratt, R., 258 Sprecher, M., 11, 17, 235, 253 Sprouse, C. T., 24 Srivanavit, C., 28 Stade, W., 28, 226, 260 Stapley, E. O., 144 Starnes, W. H., jun., 71 Starostin, A. D., 280 Stein. G.. 138 Steiner, P. R., 74

Author Index

29 1

Steinert, A., 275 Stelzer, O., 53 Stenhouse, 1. A., 269 Stepanov, B. I., -1, 61, 189, 201, 205, 206 Sternbach. H.. 135 Steuber. F. W.. 28. 226. 260 Stevens, C. L., 148 Stewart, A. P., 43, 56 Stillwell. R. N.. 279 Stirling,’C. J. M.,25 Stockel, R. F., 80 Stokes, D. H., 74 Stone, R. G., 267 Stopes, P. M., 179 Stork, G., 186 Stowring, L., 129 Stroh, J., 171, 187, 188,227 Strominger, J. L., 142 Strosser, M. T., 139 Struck, R. F., 154, 264 Strukov, 0. G., 88, 265 Studnev, Yu. N., 159 Sturtevant, J . M., 126 Sturtz, G., 185 Subramanian, S., 261 Sudo, R., 50, 51 Sudokova, E. V., 67 Sugimura, T., 139 Sugita, M., 143 Sulston, J., 133 Sumiki, Y., 179 Summers, J. C., 44 Sunamoto, J., 104 Sunder-Plassman, P., 177 Surmatis, J. D., 20, 179 Suschitzky, H., 232 Susuki, M., 17 Sutherland, 1. O., 155 Suzuki, S., 138 Sventitskii, E. N., 241 Swan, J. M., 117, 153 Sweeley, C. C., 142, 279 Swierkowski, M., 133 Switkes, E. S., 220 Swysen, P., 270 Symes, K. C., 81 Symons, M. C. R., 261 Symons, R. H., 128 Synder Crittenden, E. R., 153 Szabolcs, J., 179 ~I

Tabata, T., 281 Taborsky, G., 154 Tagaki, M., 103, 104 Takahashi, S., 136 Takai. K.. 170 Takanohashi, K., 94, 119 Takeishi, K., 133 Takenishi, T., 94, 119 Takizana. T., 158 Tamurd, z., 143 Tang, R., 28,247,262 Tantasheva. F. R.. 8 Tapiero, C.‘ M., 123 Tarasov, V. V., 88 Taskina, A. L., 52 Tavs, P., 7, 236

I

Taylor, A., 15, 230 Taylor, D., 212, 218 Taylor, I. C., 10 Tazawa, I., 124 Tebby, J. C., 8, 9, 10, 156, 245, 255 Tee. 0. S.. 242 Teraji, T.,’ 168 Terauchi, K., 91, 115, 222, 224, 261 Thaller, V., 156 Thewalt, U., 28, 274 Thomas, L. C., 262 Thomas, W. A., 66, 256 Thommen, R., 20, 179 Thompson, J. L., 175 Thompson, Q. E., 78 Thomson, C., 227, 232, 260 Timofeeva, T. N., 88, 240 Tinoco, I., jun., 133 Titov, S. S., 217 Tittensor, J. R., 181 Tkachenko, E. N., 187, 203 Todd, M. J., 230, 231 Todd, S. M., 216 Todd Miles, H., 133 Toii. L.. 134 Toimachev, A. I., 205 Tolman, C. A., 243 Tolochko, A. F., 168 Toma, F., 130 Tomalia, D. A., 19 Tomaschewski, G., 66 Tomilov, A. P., 59 Tomioka, H., 56, 115, 223, 254 Tomita, K., 118 Tor-Poghossian, G., 201 Toth, G., 179 Townsend. L. B.. 134 Trampe, G., 13, $5 Tran, L. T., 258 Trentham, D. R., 152 Trippett, S., 21, 23, 43, 57, 61 Trivedi, B. C., 21, 115 Trofimov, B. A., 69 Tronchet, J. M. J., 180 Trotter, J., 219 Trowbridge, D. B., 1 129 Tsivunin. V. S.. 45 Tsmur, Y . Y., 51 Ts’o, P. 0. P., 132 Tsolis, A., 26, 157, 280 Tsuboi. M.. 136 Tsuboyama. K., 279 Tsuda; E., 168 Tsuyuki, E., 281 Tsvetkov. E. N.. 66 Tukhar’, ’A. A., ‘201 Tulimowski, Z., 117, 257 Turner, L. P., 136 Tvsetkov. E. N., 118 Tyka, R.; 71 Tyndall, Z., 19 Tvssee. D. A.. 280 Tkchach, A.,’275 ’

~

Ubasawa, M., 132 Uchida, T., 133 Ueda, T., 70, 222 Uesugi, S., 124 Uhlenhut. G.. 113 Ukita, T.; 133, 136 Usher, D. A., 99, 127 Utsunomiya, Y., 281 Utter, M. F., 138 Utvary, K., 195, 202 Vakhrushev, L. P., 19 Valetdinov, R. K., 8, 12 Van den Berg, G. R., 152 Van der Kelen, C. P., 1 van de Sande, J. H., 130 Van Gheman, M., 17 Van Hooidonk, C., 112, 152 Van Reijendam, J. W., 183 van Tamelen, E. E., 160 Van Wazer, J. R., 236 Vasil’ev, A. F., 258 Vasil’eva, M. N., 38 Vdovina, E. S., 88 Veillard, A., 241 Vengadabady, S., 125 Verkade, J. G., 250, 251 Vetessv. Z.. 218 Vig, d.’P.,-177 Vilkov, L. V., 258, 267 Vilbmin. M.. 130 Vinogradova,’V. S., 37, 38, 77 Virkhaus, R., 11 Vives, J.-P., 106 Vogt, W., 109, 143 Voigt, D., 270 Volkova, N. V., 95 Vollhardt, K. P. C., 183 Vollmer, H., 238 von der Haar, F., 136 von Halasz, S. P., 198 von Tigerstrom, R. G., 132 Vorsina, I. A., 263 Voznesenskaya, A. K., 32, 37 Wadsworth. W.. 105 Waggoner, A. S:, 153 Wagner, H., 159 Wagner. T. E.. 136 Waze, N.-E., 10, 255 Wakefield, Z. T., 218 Wakselman, M., 96, 101 Wald, H.-J., 197 Walker, B. J., 258 Wallick H., 144 Walser,’A., 20, 179 Walsh, E. J., 215 Walz, F. G., jun., 127, 280 Wampler, D. L., 118, 129, 275 Wanermen. W.. 1 Wang, J. H., 145 Ward, D. C., 127 Ward, R. S.,9, 10, 156,245 Warfield. A. S.. 136 Warren,’C. D.,’149

Author Index

292 Warren, S. G., 118, 129, 275 Wass, M. N., 265 Wassermann, E., 78 Watson, D. G., 118, 129, 275 Watson, J. G., 138 Watson, P., 218 Weber, H., 130, 243 Weber, W., 200, 242 Weedon, B. C. L., 177, 179 Weglewski, J., 72 Wei, I. Y., 245 Weill, J. D., 139 Weingand, C., 191, 242 Weinshenker, N. M., 175 Weinstein. B.. 179 Weiss, J.,‘220, 275 Weiss, R. G., 12, 50, 233, 24 1 Wellman, G., 181 Wendler, N. L., 108 Wendt, G., 149 Wentworth. M. A.. 140 Westcott, L. D., jun., 157, 221, 264 Westheimer, F. H., 29, 97, 99, 127, 244, 280 Wheatland, D. A., 241 Whiffen, D. H., 262 Whistler, R. L., 138 White. G. F.. 103 White; W. D:, 250 Whitehouse, P. A., 177 Whitesides, G. M., 48, 242 Whitlow, S. H., 219 Wiber, E., 17 Wieber, M., 31 Wiebers, J. L., 136, 279 Wieland, T., 95, 146 Wightman, R. H., 131 Wiley G. R 48 Wilfidger, H? J., 31 Willard, J. M., 138 Williams, D. A., 217 Williams, D. H., 9, 10, 156, 245 Williams, F. R., 133

Williams, L. D., 99, 280 Williams, P. J., 179 Williams, V., 154 Willson. M., 35, 241 Wilson,’G. L., 44 Wilson, I. F., 245 Wilson, J. B., 154 Wilson, L. A., 241 Wingeleth, D. C., 52 Winstein, S., 256 Wltschard, G., 262 Wittip. G.. 18. 228 Wittmann; R.; 132 Woenckhaus, C., 138 Wolf, D. P., 153 Wolf, F. J., 144 Wolf, M. R., 197 Wolf, R., 34, 36, 88, 252, 270 Wolfsberger, W., 204 Wolring, G. Z., 152 Wong, D. Y., 81, 157 Wong, P. C. L., 146 Wong, P. K., 221 Wood. H. C. S.. 155 Wood; H. G., 138 Wood, N. F., 6, 221 Woodford. W.. 19 Woodruff,’H. B: 144 Woods, A. E., 138 Wormald, J., 220 Wray, J. E., 177 Wright, A., 142 Wright, J. B.. 232 Wright; S. H: B., 117, 153 Wulff, J., 238 Wunsche, C., 277 Yager, W. A., 78 Yagi, H., 232 Yakshin, V. V., 3 Yakubovich, A. Ya., 38, 194. 206. 238 Yamada, T., 130 Yamada, Y., 119 Yamamoto, A., 242 Yamamoto, H., 164, 165 Yamanaka, T., 232

Yamasaki, M., 133 Yamazaki, A., 119 Yankowsky, A. W., 251 Yanotovskii, M. Ts., 173 Yardley, J. P., 177, 184 Yasnikov, A. A., 95 Ykman, P., 171 Yoshida, H., 222 Yoshida, M., 133 Yoshikawa, M., 94, 119 Yoshioka, M., 143 Younas, M., 101 Yunis, A. A., 153 Yurchenko, R. I., 201,205 Zagorets, P. A., 281 Zaitseva, E. L., 194, 206, 238 Zalesskii, G. A., 196 Zanke, D., 66 Zaret, E. H., 14,47, 80, 97, 228 Zaripov, N. M., 274 Zbiral, E., 156, 171, 187, 188, 227 Zeliger, H. I., 245 Zhdanov, Yu. A., 180,181 Zheltukhin, V. F., 72 Zhelvakova, E. G., 149 Zhenodarowa, S. M., 133 Zhivukhin, S. M., 206,215, 217 Zhmurova, I. N., 201, 205 Ziegler, M. L., 220, 275 Zimin, M. G., 57, 89 Zimnicki, J., 185 Zinbo, M., 148, 279 Zingaro, R. A., 66, 227, 260 Zmudzka, B., 122, 133 Zon, G., 5, 6, 28, 29, 60, 242, 247 Zurfluh, R., 179 Zwierzak, A., 86, 98, 117, 257 Zwierzak, R., 234 Zyablikova, T. A., 67 Zykova, T. V., 45