Organosphophorus Chemistry (Specialist Periodical Reports) (v. 4)

A Specialist Periodical Report

Organophosphorus C hem istry Volume 4

A Review of the Literature Published between July 1971 and June 1972

Senior Reporter

S. Trippett, Department of Chemisfry, The Universify, Leicester Reporters R. S. Davidson, The Universify, Leicesfer

N. K. Hamer, Cambridge University D. W. Hutchinson, University of Warwick R. Keat, Glasgow Universify

J. A. Miller, University of Dundee

D. J. H. Smith, The Universify, Leicesfer J. C. Tebby, North Sfaffordshire Polyfechnic B. J. Walker, Queen's Universify of Belfast

@ Copyright 1973

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

ISBN: 0 85186 036 2 Library of Congress Catalog Card No. 73-268317

Organic formulae composed by Wright’s Symbolset method

PRINTED IN GREAT BRITAIN BY JOHN WRIGHT AND SONS LTD., AT THE STONEBRIDGE PRESS, BRISTOL BS4 5NU

Foreword

The period covered by this Report has, in most areas of organophosphorus chemistry, been one of consolidation with few new exciting advances. Notable exceptions have been in the study of stable quinquecovalent phosphoranes and of their pseudorotation phenomena, and in the application of molecular orbital calculations to studies of bonding in phosphorus compounds. These together promise a new understanding of the factors which affect stability and reactivity in organophosphorus chemistry and this is bound to provide a powerful stimulus to future progress. The volume of publication continues to increase and, in order to keep the Report to its present size, Reporters have had to be more selective. However, we hope that all significant publications have been covered.

S. T.

Contents ~-

Chapter 1 Phosphines and Phosphonium Salts By D. J. H. Smith

I Phosphines 1 Preparation From Halogenophosphine and Organometallic Reagent From Metallated Phosphines By Reduction Miscellaneous 2 Reactions Nucleophilic Attack on Carbon Activated Olefins Activated Acetylenes Carbonyls Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous

1

1 2 3 4 5 5

5 6 7 8 11 13

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

15 18 18 21 22

I II Phosphorins and Phospholes 1 Phosphorins Preparation React ions 2 Phospholes

23 23 25 27

Chapter 2 Qu i nq uecovalent Phosphorus Corn po unds By S. Trippett 1 Introduction 2 Ligand Reorganization and Structure

29 29

vi

Contents 3 Acyclic Systems

31

4 Four-membered Rings

33

5 Five-membered Rings 1,3,2-Dioxaphospholans 1,3,2-Dioxaphospholens 1,2-Oxaphospholans 1,2-Oxaphospholens 1,3,2-Oxazaphospholans 1,3,5-Oxazaphospholens Miscellaneous 6 Six-co-ordinate Species

37 37 39 41 42 43 44 46 49

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller 1 Halogenophosphines Physical Aspects Reactions Nucleophilic Attack by Phosphorus Electrophilic Attack by Phosphorus Biphilic Reactions with Dienes and with Unsaturated Carbonyl Compounds Miscellaneous

51 51 52 52 53

2 Halogenophosphoranes Preparation and Structure Reactions

62 62 65

3 Phosphines containing a P-X Bond (X = Si, Ge, or Sn)

71

Chapter 4 Phosphine Oxides and Sulphides By J. A, Miller 1 Physical Aspects 2 Preparation From Secondary Phosphine Oxides and Sulphides By Arbusov and Related Reactions By Oxidation of Phosphines By Miscellaneous Routes

60 60

73

74 74 77 77 79

Contents

vii

3 Reactions At the P=O or P=S Group Additions to Unsaturated Phosphine Oxides Miscellaneous Reactions

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

79 79 81 82

87

2 Phosphorous Acid and its Derivatives Nucleophilic Reactions Attack on Saturated Carbon Attack on Unsaturated Carbon Attack on Nitrogen Attack on Oxygen Attack on Halogen Electrophilic Reactions Rearrangements Cyclic Esters of Phosphorous Acid Miscellaneous Reactions

87 87 87 89 103 104 107 109 112 113 114

3 Phosphonous and Phosphinous Acids and their Derivatives

115

Chapter 6 Quinquevalent Phosphorus Acids By N. K. Hamer 1 Phosphoric Acid and its Derivatives Synthetic Methods Solvolyses of Phosphoric Acid Derivatives Reactions

117 117 121 126

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

129 129 133

3 Miscellaneous

141

137

...

Contents

Vlll

Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson 1 Introduction

143

2 Mono-, Oligo-, and Poly-nucleotides Mononucleotides Nucleoside Polyphosphates Oligo- and Poly-nucleotides Analytical Techniques and Physical Methods

143 143 151 153 158

3 Coenzymes and Cofactors Nucleoside Diphosphate Sugars Vitamin B, and Related Compounds Other Cofactors

158 158 160 161

4 Naturally Occurring Phosphonates

165

5 Oxidative Phosphorylation

166

6 Sugar Phosphates

167

7 Phospholipids

169

8 Enzymology

171

9 Other Compounds of Biochemical Interest

1 74

Chapter 8 Ylides and Related Compounds By S. Trippett 1 Methylenephosphoranes Preparation React ions Halides Car bonyls Miscellaneous

176 176 177 177 178 183

2 Phosphoranes of Special Interest

187

3 Selected Applications of Ylides in Synthesis Natural Products Macrocyclic Compounds Carbohydrates

192 192 195 199

4 Selected Applications of Phosphonate Carbanions

ix 199

5 Ylide Aspects of Iminophosphoranes

203

Contents

Chapter 9 Phosphazenes By R. Keaf 1 Introduction

205

2 Synthesis of Acyclic Phosphazenes From Amides and Phosphorus(v) Halides From Cyano-compounds and Phosphorus(v) Halides From Azides and Phosphorus(I1r) Compounds Other Methods

205 205

3 Properties of Acyclic Phosphazenes Halogeno-derivatives Alkyl and Aryl Derivatives

212 212 216

4 Synthesis of Cyclic Phosphazenes

219

5 Properties of Cyclic Phosphazenes General Halogeno-derivatives Amino-derivatives Alkoxy- and Aryloxy-derivatives Aryl and Alkynyl Derivatives

223 223 224 225 228 23 1

6 Polymeric Phosphazenes

233

7 Molecular Structures of Phosphazenes Determined by Diffraction Methods

234

207 209 210

Chapter 10 Radical, Photochemical, and Deoxygenation Reactions By R. S. Davidson 1 Radical and Photochemical Reactions

236

2 Deoxygenation and Desulphurization Reactions

245

Contents

X

Chapter 11 Physical Methods By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy Chemical Shifts and Shielding Effects 8P

PIx1Compounds

PIv Compounds Pv Compounds Isotopes effects 6C

8H

Studies of Equilibria, Reactions, and Solvent Effects Pseudorotation Restricted Rotation Inversion, Non-equivalence, and Configuration Spin-Spin Coupling JPP and JPM JPC

'JPH JPC*H

JPXH and JPXC,H Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies

250 250 250 252 254 254 255 255 256 257 259 26 1 263 264 264 266 268 268 270 27 1

2 Electron Spin Resonance Spectroscopy

272

3 Vibrational Spectroscopy Band Assignment and Stnict ural Elucidation Stereochemical Aspects Studies of Bonding

274 274 276 277

4 Microwave Spectroscopy

278

5 Electronic Spectroscopy

279

6 Rotation and Refraction

28 1

7 Diffraction

282

8 Dipole Moments, Conductance, and Polarography

286

9 Mass Spectrometry

287

xi

Contents 10 pK and Thermochemical Studies

290

11 Surface Properties

291

12 Radiochemical Studies

292

Author I ndex

293

Abbreviations

AIBN DBU DCC DMF DMSO g.1.c. HMPT NBS n.q.r. PPi TCNE

THF t.1.c.

bisazoisobutyronitrile 1,5-diazabicyclo[5,4,O]undec-5-ene dicyclohexylcarbodi-imide NN-dimethylformamide dimethyl sulphoxide gas-liquid chromatography hexamethylphosphorictriamide N-bromosuccinimide nuclear quadrupole resonance inorganic pyrophosphate tetracyanoethylene tetrahydrofuran thin-layer chromatography

1

Phosphines and Phosphonium Salts BY D. J. H. SMITH

PART I: Phosphines 1 Preparation From Halogenophosphine and Organometallic Reagent.-Unsymmetrical tertiary phosphines (1) have been obtained by the stepwise addition of organometallic reagents of different reactivity to dich1orophenylphosphine.l Dia1kylphenylphosphines and dia1kylst yrylphosphines have been prepared by the reduction of tetrachlorophenylphosphoranewith Grignard reagents.2 The reaction of dichlorophenylphosphine with a large excess of toluene in the presence of aluminium chloride in an autoclave at 210 "Cgave ditolylphenylphosphine.3 The ligand o-diphenylphosphinobenzyldimethy 1silane (2) has been prepared from chlorodiphenylphosphineand the corresponding Grignard reagent.* PhPCl, +ArlZnC1

PhAr'PCI

Ar2Li

Ar'Ar2PhP Arl = .-C,,H, (l' Ar2 = PhC,H,

_I_,

Ph,PCI Mg

a

G. Wittig, H. Braun, and H . 4 . Cristau, Annalen, 1971, 751,17. B. V. Timokhin, E. F. Grechkin, N. A. Tran'kova, and 0. A. Yakutina, J. Gen. Chem.

(U.S.S.R.), 1971, 41, 99. H. Nohira, Y. Hirayama, and T. Hattaha, Yuki Gosei Kagaku kyokai Shi, 1971, 29, 424 (Chem. Abs., 1972,76, 14 649). H. G. Ang and P. T. Lau, J. Organometallic Chem., 1972, 37, C4.

1

2

Organophosphorus Chemistry

A variety of phosphinoacetylenes has been prepared by reaction of an acetylene and a chloroyhosphine in the presence of butyl-lithium.6 The synthesis of several quadridentate ligands containing both phosphorus and arsenic donor atoms, e.g (3), from a chlorophosphine and the appropriate lithio-derivative has been described.6

(Mp-c' +

I

(3)

From Metallated Phosphines.-The polymeric ligand (4) has been formed from chloromethylated styrene-divinylbenzene copolymer and lithium diphenylphosphide.' Trimethylsilylation of potassium phenylphosphide gave the phosphine ( 5 ) , which on treatment with bromine gave phenylphosp horus. (Trimethylstanny1)phosphine (6) has been prepared in high yield from trimethyltin chloride and lithium tetraphosphinoaluminate.B

PhPHK

+ Me,SiCI

Rr2

--+ PhPHSiMe, -+

Me,SiBr

+

HBr

+

+(PhP),

(5)

Na,P

+ ClC0,Et

--+ P(CO,Et), ( 7 ) 2'>'>r,

A. J. Corty, N. K. Hota, T. W. Hg, H. A. Patel, andT. J. O'Connor, Canad. J. Chem., 1971, 49,2706.

' *

J. W. Dawson and L. M. Venanzi, J. Chem. SOC.( A ) 1971, 2897. M. Capka, P. Suoboda, M. Cerny, and J. Hetflejs, Tetrahedron Letters, 1971, 4787. M. Baudler and A. Zarkadas, Chem. Ber., 1971, 104, 3519. A. D. Norman, J. Organometallic Chem., 1971, 28, 81.

3 The elusive tricarbethoxyphosphine (7) has been obtained from the reaction of trisodium phosphide and ethyl chloroformate.1° Ethylphosphorus reacts with various amounts of phenyl-lithium to give the lithium phosphides (8), which are more reactive than ethylphosphorus towards phenyl-lithium and can react further to give complex mixtures of other lithium phosphides.ll Unsaturated phosphines (9) have been prepared with high stereospecificity by the addition of di-t-butylphosphine to

Phosphines and Phosphonium Salts

(EtP), But,PH PhPHK

+

+ PhLi * EtLiP-P(Et),-P(Et)Ph

+ HCECX

PhC=CH

-

(8)

d

(9) X

11 =

0-3

(But),PCH=CHX = CN(cis) or CO,Me(/rcm)

(PhCH=CH),PPh

+

PhCH=CHPPhK

(10)

H201

PhCH=CHPHPh (1 1)

( I 2) 73%

activated acetylenes in ether.12 Treatment of phenylacetylene with potassium phenylphosphide gave a mixture of the phosphines (10) and (ll).l3 The unusual phosphorus heterocycle (12) can be prepared in high yield by the reaction of pentaphenylcyclopentaphosphane with potassium followed by the addition of an equimolar amount of dichloromethane.14 By Reduction.-Cyclopolyphosphines

can be reduced electrochemically to primary phosphines.15 For example, phenylphosphorus when electrolysed in 8% methanol with platinum and mercury electrodes gave phenylphosphine. A two-stage reduction of o-nitrophenylphosphonate to (o-aminopheny1)phosphine has been described.16 l1

A. W. Frank and G . L. Drake, J. Org. Chem., 1971,36,3461. 0 . Glemser, 2. anorg. Chem., 1971, 385, 47.

la

R. G. Kostyanovskii, Y. I. El'natanov, and V. G. Plakhanov, Bull. Acad. Sci. U.S.S.R.,

l*

K. Issleib, H. Boehne, and C. Rockstroh, J. prakt. Chem., 1970,312, 571 (Chem. Abs.,

l4

M. Baulder, J. Vesper, P. Junkes, and H. Sandmann, Angew. Chem. Internat. Edn.,

1971, 20, 2244,

l6

l6

1971, 74, 112 133).

1971, 10, 940. A. Tzschach, H. Matschiner, and E. Reiss, Ger. (East) P. 79 728 (Chem. Abs., 1972,76, 14 714). K. Issleib, H. U. Bruenner, and H. Oehme, Orgunometullic Chem. Synthesis, 1971,1,161 (Chem. Abs., 1971, 74, 112 130).

4

Organophosphorus Chemistry Miscellaneous.-Polytertiary phosphines and phosphinoarsines have been prepared by the base-catalysed addition of phosphorus-hydrogen or arsenic-hydrogen bonds to vinylphosphines or ethyny1pho~phines.l~The same type of reaction was utilized to prepare the diphosphine (1 3). Radical addition of primary phosphines to vinylphosphines has also been

H2C=CHSiX3

+

Me,PH

I1 v

> Me,PCH,CHzSiX3 (15) X = F o r CI

shown ID to give diphosphines (14). Similarly photochemical addition of dimethylphosphine to vinylhalogenosilane gave (dimethy1phosphino)ethylsilanes (15) in high yield.20 Tertiary phosphines have been partially resolved 21 by complexation with the asymmetric palladium(I1) complex (16). Treatment of this complex with racemic phosphine gave (17), phosphine of low rotation being recovered from the mother liquor. The enantiomeric phosphine can be

AS1ArzAAr3p Rso:3~i IICHO >

[ A r ' A r z A r 3 ~ C t l , 0 H ] RS0,(+)

(18) CH2-

+ As'Ar2Ar3P (-1

R-Q" l7 l8

l9 2o

a1

R. B. King and P. N . Kapoor, J. Amer. Chem. Soc., 1971,93, 4158. R. B. King and P. N. Kapoor, Angew. Chem. Internat. Edn., 1971, 10, 734. K. Issleib and H. Weichmann, 2. Chem., 1971, 11, 188 (Chem. Abs., 1971, 75, 63 899) J. Grobe and U. Moller, J. Organometallic Chem. 1971, 31, 157. S. Otsuka, A. Nakamura, T. Kano, K. Tani, J. Amer. Chem. Soc., 1971, 93,4301.

Phosphines and Phosphonium Salts

5

generated by addition of bis(dipheny1phosphino)ethane to (17). The reaction of triarylphosphines with paraformaldehyde and one half of an equivalent of (+)-camphor-10-sulphonicacid gave a crystalline sulphonate (1 8). Optically active phosphine was isolated from the mother liquor. A review of the preparation of phosphines and other organophosphorus compounds and the stereochemistry of their reactions has appeared.22 2 Reactions Nucleophilic Attack on Carbon.-Activated OleJins. Triarylphosphines react with 7,7,8,8-tetracyanoquinodimethane(19) in the presence of water and a trace of hydrochloric acid to give a quantitative Ar,P

+ (CN),C O

C K N ) ,

H,O-HC

Ar,PO Ph,P

+

+

(CN)*CHO C H ( C N 1,

I

XC,H,CH=C(CN)z HtO-H

-

+

-

P h t3 $ C H (C6H, X )* C H (CN ) CON H (20) X = H, p-Me0, p - M e , or /I-NO, Ph

‘h

0

0

PI1

Ph,P’

‘$,

‘b

Ptl

PI1 H

Ptl

PI1

C02R H-0

R

=

Me or Pti

H za

CO-

H. Christol and H. J. Cristau, Ann. Chim.(France), 1971, 179 (Chem. Abs., 1972, 76, 13 277).

6

Organophosphorus Chemistry

yield of 1,4-bis(di~yanomethyl)benzene.~~ The authors propose that the reaction proceeds via a phosphinium radical cation. The reaction of triphenylphosphine with a series of benzylidenemalononitrilesin chloroform in the presence of hydrochloric acid 24 gave the corresponding monoamides (20), presumably by way of nucleophilic addition followed by acid-catalysed hydrolysis. An interesting compound, formulated as (21), is formed from The the reaction of triphenylphosphine with diphenylcycl~propenone.~~ reactions of (21) with methanol and trans-a-phenylcinnamic acid occur by nucleophilic attack on the keten rather than the ylide group. Activated Acetylenes. The unstable 1 : 2 adduct formed from the reaction of triphenylphosphine and dimethyl acetylenedicarboxylate at - 50 “C is now thought 26 to have the cyclopropene structure (22); the PhP X

X IF

>c-c,c-x

&J ?.--.

(22) X

=

CO,Me

(22) X

=

C0,hIe Me0 X

Ph,P a3

25

M. P. Naan, R. L. Powell, and C. D. Hall, J. Chem. SOC.(B), 1971, 1683. R. L. Powell and C . D. Hall, J. Chem. SOC.(C), 1971, 2336. A. Homada and T. Takizawa, Tetrahedron Letters, 1972, 1849. N. E. Waite, D. W. Allen, and J. C. Tebby, Phosphorus, 1971, 1, 139.

7

Phosphines and Phosphoniiim Salts

adduct reacts with triphenylphosphine in methanol or chloroform to give the 1,4-diphosphorane (23). The stable products (24) and (25) are thought to be formed from rearrangement of (22) as shown. The product from the reaction of tri-p-tolylphosphine and excess of dimethyl acetylenedicarboxylate has been shown 27 by X-ray crystallography to be (26). Carbonyls. The reaction of diphenylphosphine with methyl pyruvate gave (27), isolated as the oxide,2Ewhereas reaction of tributylphosphine OH PhzPH

I

+ MeCOC0,Me

Ph2P-C-CO,Me

I

Me

(27)

Bu3P

0I +

+ MeCOC0,Me

+

MeC-PBu,

Me-E-O-PBu3 I C02Me

I

C02Me

J

Me02C(Me)C=C( Me)C02Me

(28)

with methyl pyruvate is reported 29 to lead to a mixture of cis- and transalkenes (28). 1,3-Oxaphospholans (29) are obtained from secondary phosphines and aldehydes or ketones.so Similarly, condensation of (o-aminopheny1)phosphine with carbonyl compounds l6 gave substituted lY3-benzazaphosPhP(H)CH,CH,OH

4-

R2, R'

,C=O

--+

ph-p

n

(29) R1 = H or Ph R2 = Me or Ph R', R2 = (CHJ,

aPH2 + R$o

NHZ

27 28

30

H

2 R ; f @

R2

(30):2

-

R'

HorMe H, Et, or Ph

0. Kennard, W. D. S. Motherwell, and J. C. Coppola, J. Chem. SOC.(C), 1971, 2461. A. N. Pudovik, I. V. Gur'yanova, G. V. Romanov, and A. A. Lapin, J, Gen. Chem.

(U.S.S.R.),1971, 41, 710. A. N. Pudovik, I. V. Gur'yanova, V. P. Kakurina, and N. P. Anoshina, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1237. H. Oehme, K. Issleib, and E. Leissing, Tetrahedon, 1972, 28, 2587.

Organophosphorus Chemistry

8

pholines (30). A full report has appeared on the reaction of secondary phosphines with ethanolic carbon disulphide in the presence of base31 to give the thioformates (3 1) or (32), depending upon the phosphine used. The position of equilibrium in solution depends primarily on the inductive effects of the substituent on phosphorus. Lithium diphenylphosphide in THF reacts with epoxides stereospecifically. Quaternization of the phosphorus of the product generally led directly to the alkene with inversion of stereochemistry relative to the starting epoxide :32

Nucleophilic Attack at Halogen.-Allylic alcohols have been converted into the chloride without rearrangement by the use of the triphenylphosphine-carbon tetrachloride reagent.33 Use of the same system as a chlorinating agent has been extended to the reaction with enolizable ketones.34 Six-membered-ring ketones gave predominantly enyl halides whereas smaller-ring ketones gave predominantly exocyclic dichloromethylene compounds. The reaction of triphenylphosphine-carbon tetrahalide with cis-2-phenyl-1,3-dioxan-5-01 (33) gave a mixture 35 of the diastereomeric 1,3-dioxolans (34).

(33)

(34)

Further reports of the reaction of tris(dimethy1amino)phosphine and carbon tetrachloride with aldehydes 36 and esters or amides of trichloroacetic acid3' have appeared. Addition of tertiary phosphines to the imide (35) gave (36) after h y d r ~ l y s i s . ~ ~ 31

32

33 34 35

36

37

s8

0. Dahl, Acta Chem. Scand., 1971, 25, 3163. E. Vedejs and P. L. Fuchs, J. Amer. Chem. Soc., 1971, 93,4070. E. I. Snyder, J . Org. Chem., 1972, 37, 1466. N. S. Isaacs and D. Kirkpatrick, J. C. S. Chem. Comm., 1972, 443. R. Aneja and A. P. Davies, J. C. S. Chem. Comm., 1972, 722. G. Lavielle, J.-C. Combert, and J. Villieras, Bull. Suc. chim. France, 1971, 2047. G. Lavielle, J.-C. Combret, and J. Villieras, Compt. rend., 1971, 272, C, 2175. M.-F. Chasle and A. Foucaud, Bull. Soc. chim. France, 1972, 1535.

9

Phosphines and Phosphonium Salts

I

(35)

H,O

Dehydration reactions using the tertiary phosphine-carbon tetrachloride adduct have appeared quite regularly in the literature again this year. Among those reported have been the dehydrations of oximes to nitriles,ss carboxylic acids to anhydride^,^^ and the amides (37) to the cumulenes (38).40 Further reaction of the dehydration product from treatment of the RINHC( R2)=C(C0,Et)CONHR3 R1 = Ar (37) R2 = Me

I

R3 = Bu' PhaP-CCI,

RIN= C ( R2) C (C0,Et ) =C=N R3

(38)

Ar$~r~Hz

Ph P-CCI

wAr2 r

Ar'

2

CN

N

(39)

Ar'-C=C I

..

:N _ .

,CN 'AT'

kh3P

Ar'-C=C, I

,CN

Ar2

N, PPh,

(40) 40

41

R. Appel, R. Kleinstiick, and K.-D. Ziehn, Chem. Ber., 1971, 104, 2025. J. Coerdeler and C. Lindner, Tetrahedron Letters, 1972, 1519. B. Castro and J.-R. Dormoy, Buff. SOC.chim.France, 1971, 3034.

10

Organophosphorus Chemistry

azirine derivative (39) with triphenylphosphine gave the triphenyliminophosphorane (40),possibly via a nitrene intermediate.4a The formation of a peptide bond using tertiary phosphines and a halogenomethane has been studied in more detai1.43~44Trisaminophosphines and carbon tetrachloride are the reagents of choice. Tripeptides are formed in high yield and with high optical purity. The simultaneous action of triphenylphosphine and carbon tetrachloride 45 on the sulphonyl compounds (41), followed by triethylamine, gave iminophosphoranes (42). Ph3P

+ CCl4 + H,NSO,R jEhN

Ph,P=Pu'-SOzR

(42) R

=

(41)

+ + CHCl, + Et3NHCl-

Ph, NH,, or NMe,

Several debrominations using triphenylphosphine have been reported. Stilbene dibromides and other vicinal dibromides are debrominated stereospecifically in an anti-eliminati~n.~~ 9,9-Dibromofluorene and dibromodiphenylmethane (43) have been converted into the corresponding ethylene,*' and the compounds (44)gave moderate yields of aroyl cyanides when fused with triphenylpho~phine.~~ Ph,CBr,

Ph,P benzene

> PhzC-Br

*Ph2C-CPh2 I

(43)

I

~

+ PhZC=CPhz

Br Br

ArCOC(Br)=NOH

(44)

+ Ph,P

---+

ArCOCN

The vinyl ether (45) and triphenylphosphine gave the phosphonium salt (46). The reaction is thought to proceed by initial attack at halogen followed by quaternization of the phosphine by the intermediate formed.49 Hydrolysis of (46) gave (1-formylethyl)triphenylphosphoniumbromide (47). When triphenylphosphine is heated with the bromoesters (48) quaterniza42 43

44

45 46

47

49

T. Nishiwaki, J . C . S. Chem. Comm., 1972, 565. S. Yamada and Y. Takeuchi, Tetrahedron Letters, 1971, 3595. T. Wreland and A. Seeliger, Chem. Ber., 1971, 104, 3992. R. Appel, R. Kleinstiick, and K.-D. Ziehn, Chem. Ber., 1971, 104, 2250. I. J. Borowitz, D. Weiss, and R. K. Crouch, J. Org. Chem., 1971, 36, 2377. I. J. Borowitz, P. E. Rusek, and P. D . Readio, Phosphorus, 1971, 1, 147. M. I. Shevchuk, S. T. Shpak, and A. V. Dombrovskii, Zhur. org. Khirn, 1971, 7, 1004 (Chem. Abs., 1971,75, 63 350). L. Reichel and H.-J. Jahns, Annalen, 1971, 751, 69.

11

Phosphines and Phosphonium Salts Br I Me-C=CHOEt

‘ I I

+ Ph3P - - - - - - - - - + MeC =CHOEt

(45)

Br-

‘PPh,

H,O

MeCHCHO I Br+PPh3

Ph3P

+

Br3:i --+-

OEt

(48)

RL = CO,Et R2

=

PI

Ph3PEt

LL5

+ C02 +

R1R2C=CH, (49)

C0,Et or H

tion occurs;6othis is followed by a cyclic elimination to give ap-unsaturated carbonyls (49). Nucleophilic Attack at Other Atoms.-The formation of iminophosphoranes from tetrazolopolyazines (50) and triphenylphosphine has been studied kinetically.61 Evidence was produced which indicated that the reaction occurred by nucleophilic attack of the phosphine on the tetrazolo-ring. An iminophosphorane was also formed 5 2 when the diazocompound (51) was added to molten triphenylphosphine at 140 “C.

Ph& N2 Ph 1 Ph (51) Ph3P

6o

+

Ph3P

-6 -

+ PhN=NPh + HC104

Ph Ph..--

N-N=P Ph,

Ph

Ph-N-NHPh I ClO, +PPh3

D. Orth, Tetrahedron Letters, 1972, 825. T. Sasaki, K. Kanematsu, and M. Murata, Tetrahedron, 1972, 28, 2383. D. Lloyd and M. I. C. Singer, J. Chem. SOC.,(Ch. 1971 2941

12

Organophosphorus Chemistry

Azobenzene reacts readily with triphenylphosphine 53 in aqueous ethanol containing perchloric acid to yield a phosphonium salt (52). The complex formed between diethyl azodicarboxylate and triphenylphosphine is a very useful reagent for condensation reactions. The reaction of alcohols with phthalimides, in the presence of diethyl azodicarboxylate and triphenylphosphine, resulted in the formation of the corresponding N-alkylphthalimide in good yield.54 The reaction proceeds stereospecifically with complete inversion, as shown by conversion of (S)-(+)-2-octanol to (R)-(-)-2-octylamine, isolated by treatment of the initially formed phthalimide with hydrazine hydrate. Condensation between alcohols and other active-hydrogen compounds using the same reagents has also been described (Scheme l).65 Phosphorylation of alcohols by initial activation

.x

RCHXY

+

Et02CNHNHC0,Et

+

Ph,PO

Scheme 1

X Y

= =

CN or MeCO CN or C0,Et

of the alcohol by the diethyl azodicarboxylate-triphenylphosphine complex (Scheme 2) has been Ph3P

+ EtO,CN=NCO,Et

I(

EtO2CN-NTC-OEt P h 3 b -\\I0

1-

EtO,C N H- N- CO,E t RO),P0,'fh3 EtOH

J

EtO-P(OR),

II

0 53 54 55 B6

+

[ Ph,~-OEtl(RO),P02-

+

Et 0,CN HNHC0,Et

Ph3P0

Scheme 2

R. E. Humphrey and E.E . Hueske, J . Org. Chem., 1971,36, 3994. 0. Mitsunobu, M. Wada, and T. Sano, J . Amer. Chem. SOC.,1972, 94, 679. M. Wada and 0. Mitsunobu, Tetrahedron Letetrs, 1972, 1279. 0. Mitsunobu and M. Eguchi, Bull. Chem. SOC.Japan, 1971, 44, 3427.

13

Phosphines and Phosphonium Salts

Tetracyclones react with phenylphosphine to yield trans-dihydrotetracyclones (53). The reaction is thought to proceed via initial attack at oxygen.67

ph&O Ph ..-

3- PhPHz

Ph

Ph

(53)

For the reaction of triarylphosphines with radicals and related reactions see Chapter 10, Section 1. The reaction of several phosphines with diethylperoxide is described in Chapter 2. Miscellaneous.-Mislow has now found an example of a phosphine which does not obey the electronegativity rule for correlating energy barriers with pyramidal inversion in p h o s p h i n e ~ . ~ The ~ inversion barrier of the trimethoxysilylphosphine (54) is found to be 2 kcal mol-l lower than the Ph P r P Si (0 Me) (54)

analogous trimethylsilylphosphine, an effect which is ascribed to negative hyperconjugation. The reduction of hydroperoxides by triphenylphosphine in ethanol is second order. Unsuccessful attempts to inhibit the reaction by the use of free-radical traps suggest a non-radical mechanism.69 The reaction is catalysed by strong acids.60 Soluble salts of molybdenum or vanadium are lo4-lo5 times more effective catalysts than H+. The autoxidation of triphenylphosphine and phosphorus esters has been studied kinetically.61 After a short induction period the reaction gave the corresponding quinquecovalent phosphorus compounds. The intermediate (55) is probably formed by the addition of oxygen to perfluoroacyldiarylphosphines.sa Subsequent decomposition afforded diarylphosphinates (56). The oxadiazine (57) has been prepared from the reaction of carbon dioxide and ally1 isocyanate in the presence of trib~tylphosphine.~~ Dibromoketen can be generated from the reaction of trimethylsilyl tribromoacetate and triphenylph~sphine.~~ The isolated product (58) is derived from reaction with the cyclopentadiene solvent. 5' 58

6n 8o

e2 63 64

Y. Kashman and H. Ronen, Tetrahedron Letters, 1971, 3973. R. D. Baechler and K. Mislow, J . C. S. Chem. Comm., 1972, 185. R. Hiatt, R. J. Smythe, and C. McColeman, Cunad. J. Chern., 1971, 49, 1707. R. Hiatt and C. McColeman, Canad. J . Chem. 1971,49, 1712. Y. Ogata and M. Yamashita, J . C.S. Perkin I l , 1972, 730. E. Lindner, H.-D. Ebert, K. Geibeland, and A. Haag, Chem. Ber., 1971, 104, 3121. A. Etienne, B. Bonte, and B. Druet, Bull. SOC.chim. France, 1972, 242. T. Okada and R. Okawara, Tetrahedron Letters, 1971, 2801.

14 RCOPAr, -I- 0, + H,O

-

Organophosphorus Chemistry

0-0 (55) I

+

CO, -t- RH

j. O H 0 II I II Ar,P-C-OPAr,

I

R (56) R = CF,, CzF5,or C,H, Ar = Ph or MeC,H,

0

RN=C=O

Me,SiOCOCBr,

RCH=SO,

+ CO,

o//c'o/c"o (57) R

-

+ Ph,P

+ Ph,P

Bu,,P

Me,SiBr

---+

(59)

R = H or Ph X = CI or (NO,),C,H,O

I1 R,N/C,N/R I I

RCH-SO,

\P/

Ph 3

+

=

Ally1

Ph,PO -I- [Br,C=C=Ol

- so,

1

> RCH=PPh3 E&H

,

X-

RC H, P P ti X -

Phosphines and Phosphonium Salts

15

Sulphenes (59), generated from the reaction of sulphonate esters or sulphonyl chlorides with triethylamine, react with triphenylphosphine to form phosphonium saltsB5 The degree of correlation with the Hammett equation for the protonation of triarylphosphines depends on the solvent used.6s The presence of an o-anisyl group causes a small acceleration in the reaction of triarylphosphines with benzyl ~hloride.~' PART 11: Phosphonium Salts 1 Preparation The quaternization of (S)-( - )-benzylmethylphenylphosphine with aryl bromides, by the complex salt method using nickel bromide, proceeds with predominant retention of configuration at phosphorus.6s Optically active phosphonium salts are also obtained by quaternization of optically active triarylphosphines with b e n z y n e ~ . ~ ~ Allyltriphenylphosphonium chloride prepared from triphenylphosphine in excess refluxing ally1 chloride is far superior to the material synthesized from equimolar amounts of the reagents in boiling benzene because of the tendency of the product to rearrange to propenyltriphenylphosphonium chloride at the higher temperature. Allyltriphenylphosphonium bromide is stable in refluxing benzene.'O Triphenylphosphine can be quaternized by the vinyl bromide (60) to yield a phosphonium salt which on treatment with methyl-lithium followed by water gave the hydroxyphosphonium salt (61) stere~specifically.'~A

Ph,P

+

Br/Me H C0,Et

-

CH2

+

II

Ph,PCH,CCO,Et Br-

+I

i, MeLi ii, H,O

Ph,P

MMeBr-

H

,CMe, HO

(61) 65 66

6'

J. F. King, E. G. Lewars, and L. J. Danks, Canad. J. Chem., 1972, 50, 866. G. P. Schiemenz, Terrahedron, 1971, 27, 3231. W. E. McEwen, V. L. Kyllingstad, D. N. Schulz, and Y . I. Yeh, Phosphorus, 1971, 1, 145.

70

R. Luckenbach, Phosphorus, 1971, 1, 77. G. Wittig and H. Braun, Annalen, 1971, 751, 27. 0.Buchi and H. Wuest, Helu. Chem. Acta, 1971, 54, 1767. C. F. Garbers, J. S. Malherbe, and D. F. Scheider, Tetrahedron Letters, 1972, 1421.

16 Organophosphorus Chemistry convenient preparation of vinylphosphonium salts by treatment of the corresponding chloroethyl derivatives with triethylamine in dichloromethane has been described.72 The phosphinolium salt (62) has been synthesized by intramolecular quaternization of the phosphine (63) using hydrogen bromide followed by sodium arbo on ate.^^ Partial resolution of the salt was achieved by the use of silver hydrogen dibenzoyltartrate. Ph

Ph

Et-I'

Et-PH

\+

\

Br-

P 11

H

The spirophosphonium salt (64) is formed, together with some secondary phosphine oxide (65), when phosphorus trichloride is mixed with diphenylamine at 210 "C and the reaction mixture treated with water.74 Cyclic phosphonium salts (66) have been prepared by the reaction of substituted vinylphosphines with nitrilimine~.~~ Cyclization of the intermediate betaine with triethylammonium chloride is prevented by the presence of strong electron-accepting groups on the a carbon, in which case stable azo-ylides (67) are isolated. 72

73 74 76

J. M. Swan and S. H. B. Wright, Austral. J. Chem., 1971, 24, 777. C. H. Chen and K. D. Berlin, J. Org. Chem., 1971, 36, 2791. R. N. Jenkins, L. D. Freedman, and J. Bordner, Chem. Comm., 1971, 1213. V.V. Kosovtsev, V . N . Chistokletov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2676.

Phosphines and Phosphonium Salts PhZPCH=CHPh

+

+ R-C=N-N-Ph

-

17

CH-CHPh / Ph2P 'C-N=NPh I R (67)

I'

Et,NH C1-

CH,CHPh

+/

Ph,P

/

\

NPh

C=N R

/

C1-

The action of hydrogen chloride gas on a solution of (cu-acetylphenacy1idene)triphenylphosphorane (68) in benzene produced the phosphonium salt (69), a fairly strong acid, which exists entirely in a trans-enol form.76 The alkoxyphosphonium chlorides (70) have been obtained from the Ph,P=CCoPh I COMe (68)

(Me,N),P

+ CCI,

benLenc

+ ,COMe Ph,PCH, COPh

c1-

(69)

+ (Me,N),PCI

ROH

+

(Me,N),POR

cc1,-

c1-

+ CHCI,

(70) R = PhCH,, CoHln,or C,HII

+

Br CH,CH,CH2PPh,

NaOH --+[RrCH,CH,CH=PPh,l

Br(71)

CH,, + I ,CH-PPh, CH, Br-

PhzPCl

+ CaCz BrBr

'13

(72)

T. A. Mastryukova, V. Rubashevskaya, I. M. Aladzheva, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2358.

18

Organophosphorus Chemistry

reaction of tris(dimethy1amino)phosphine and carbon tetrachloride with primary Dichloroamines have been used to quaternize triphenylphosphine to give N-chloro-N-alkylaminotriphenylphosphonium chlorides in good yield.78 Cyclopropyltriphenylphosphonium bromide was isolated in high yield79from the addition of one equivalent of sodium hydroxide to the phosphonium salt (71). 2,2-Diphenylisophosphindoliumsalts (72) can be formed directly by the addition of o-xylylene dibromide to a mixture of chlorodiphenylphosphine and calcium carbide.80

2 Reactions Alkaline Hydrolysis.-The steric course of the alkaline cleavage of a variety of benzylphosphonium salts (73) has been investigated.*' The reaction proceeds with various amounts of inversion depending upon the nature of the R group. However, the alkaline hydrolysis of the phosphonium salts (74) has been shown to occur with partial retention Me

\+

Ph---P-CHoPh / R Br-

(73) Ar

=

Me.:+ Pr-P -Ar /

Ph

Br-

hle. ..+ Pr-P-C,H,, /

Ph

Br-

(75) (74) cr-ClnHi,/3-C,,Hi, or p-PhC,H,

of configuration with loss of the aryl group, whereas when only one aromatic group is present [e.g. (75) ] loss of that group with a small amount of inversion occurs on treatment with base.82 These results would seem to indicate that the phenyl group prefers the apical position in the first-formed intermediate phosphoranes, but as the amount of stereochemical control is very small, the energy differences between the various intermediates possible must also be very small, and no conclusions about the relative apicophilicities of the various aromatic and alkyl groups can be drawn. Inversion of configuration at phosphorus is found when the phosphonium salt (76) is treated with hydroxide ion, whereas the reaction of the phosphonium salt (77) with cyanide ion gave the corresponding phosphine with retention of c~nfiguration.~~ It has been shown that the cyclic cisand trans-phosphonium salts (78) are hydrolysed with complete inversion of ~onfiguration.~~ Presumably the larger ring size permits the ring to be accommodated in relatively strain free diequatorial positions in the intermediate phosphoranes. 77 7B

82 88 84

B. Castro and C. Selve, Bull. SOC.chim, France, 1971, 2296 R. M. Kren and H. H. Sisler, Inorg. Chem., 1971, 10, 2630. H. J. Bestmann and E. Kranz, Chem. Ber., 1972, 105, 2098. T. E. Snider and K. D. Berlin, Phosphorus, 1971, 1, 59. R. Luckenbach, Phosphorus, 1972,1,223. R. Luckenbach, Phosphorus, 1972, 1,229. L. Horner and R. Luckenbach, Phosphorus, 1971, 1,73. K. L. Marsi, J . Amer. Chem. SOC., 1971, 93, 6341.

19

Phosphines and Phosphoniuin Salts M':.+ Pr -P--CH2CH==CE-I, /

Ph

OH-

Br(76)

Me-,+ Ph-P-CH&H=CH? /

PhCH, Br-

CN-

Me + O=P-Pr \ Ph

Me., > Ph-'P /

+

Me I CH,=CCN

PhCH,

(77)

Me

Ph CH,Ph

Me

/ \

Ph 0

The kinetics of the alkaline hydrolysis of a series of (heteroarylmethy1)triphenylphosphonium salts have been investigated.86The rates of reaction decrease in the predicted order. The phosphorus-furan bond is broken as expected when the heteroarylphosphonium salts (79) are treated with aqueous alkali.86

The basic hydrolysis of the bisphosphonium salt (80) gave a phosphonium salt (81) and a phosphine oxide (82) in a ratio which depended upon the acidity of the solvent used. The reaction is presumed to proceed via a carbanion from which the phosphonium salt arises by protonation by the solvent and the phosphine oxide by phenyl migration from p h o s p h o r ~ s . ~ ~ The mechanism of the unexpected formation of 2-methyl-2H-benzopyran from the phosphonium salt (83), under normal Wittig conditions, has been discussed in some detail.EE The basic hydrolysis of phosphonium salts of the type (84) has been described.8BUsually the R group is lost; only in one case (85), in which 86

86

88

8B

D. W. Allen and B. G. Huntley, J. C. S. Perkin ZZ, 1972, 67. D. W. Allen, B. G. Huntley, and M. J. J. Mellor, J . C. S. Perkin ZZ, 1972, 63. E. E. Schweizer and C. S. Kim, J. Org. Chem., 1971, 36,4041. E. E. Schweizer, T. Minami, and D. M. Crouse, J. Org. Chem., 1971, 36, 4028. M. Simalty and M. H. Mebazaa, Tetrahedron, 1972, 28, 3343.

20

Organophosphorus Chemistry

-

4,

N&

I

Ph,PO

P'Ph,

CH,CH,PPh, +

n

+d )

P'-+ ,

CH,C H,P Ph Br-

2Br-

(80)

ocHoa '

Br-

base

~

0(CH,) 6 Ph

CH3

R1 = Ph, C=CPh, or CECMe

R2,R3,R4 = H, Me. or Ph (84)

P h O P h / \

NCCH,CH, Ph SbC1,(86)

I Ph

+ CH,=CHCN

21

Phosphines and Phosphonium Salts

the ring contained a phenyl group in the 2-position, was the heterocyclic ring broken. The increased rate of reaction of the phosphonium salt (86) over that of the saturated analogue (87) has been attributed to the stability of the phosphole

Additions to Vinylphosphonium Salts.-The addition of triphenylvinylphosphonium bromide to a number of active methylene compounds has been s t ~ d i e d . ~A l correlation was observed between the acidity of the active rnethylene species and the ease of formation of 2 : 1 adducts. Pyrazolinyltriphenylphosphonium salts (88) can be prepared by 1,3-dipolar addition of excess diazomethane to triphenylvinylphosphonium Thermolysis of (88) gave phosphonium salts (89) by elimination

+

CH,=CHPPh, Br-

+

R1R2CN,

-

+ J f 1R H'

N '

PPh, Br-

(88)

H (90) R2

=

H or Me

of nitrogen or pyrazole hydrobromides (90) by loss of triphenylphosphine. l-Hydroxypyrroles are formed from the reaction of the oximes (91) with triphenylvinylphosphonium bromide in the presence of base,Q3as outlined in Scheme 3. B1 g2

W. B. Farnham and K. Mislow, J. C. S. Chem. Comm., 1972, 469. E. E. Schweizer and C. M. Kopay, J. Org. Chem., 1971,36, 1489. E. E. Schwiezer and C. S. Kim, J. Org. Chem., 1971, 36,4033. E. E. Schweizer and C. M. Kopay, J. Org. Chem., 1972,37, 1561.

2

22

Organophosphorus Chemistry HO \N

II

Ph-C-C

NaH

4

-0 \N II // Ph-C-C

~

Ph,PCH=CH,

\

\

\

Ph,P=CHCH,O \ O N II 4 Ph-C-C

H

H

H

(91)

0 phlp

Ph

-Ph,PO

Ph

I

I

OH

N=&

0-

Scheme 3

Purines, pyrimidines, and nucleosides, for example cytidine, condense with the vinylphosphonium salt (92) to yield (93), which on treatment with alkali eliminate triphenylpho~phine.~~

+

Ph,PCH=CHCOMe Br(92)

+

NT

+

P h3PCH2- C =C,- M e

____,

Br- O NY - Y

O J h

H

+

or

Ph,P CH,-C=C ---Me

Br-

Me-F=C-Me \

Miscellaneous.-The carbanions (94), formed from the reaction of the corresponding phosphonium salt with sodium ethoxide and the sodium salt of t-butyl hydroperoxide, decompose in a number of ways. Migration of a phenyl group to oxygen yields the phosphine oxide (95) and formation of the alkyl ethyl ethers may be due to the intermediacy of a carbene, which is trapped by E. Zbiral and E. Hugl, Tetrahedron Letters, 1972, 439. K. Yamada, K. Akiba, and N. Inamoto, Bull. Chem. SOC.Japan, 1971, 44,2437.

Phosphines and Phosphonium Salts Ph3P-cR1R2

I

Ph2PCKLR2 L+ II

__I,

Ph2PCHK'R2 II 0

0

O-OBut

I

23

(94)

(95)

R1R2C:

+ Ph,PO + ButO-

+ R1R2COEt + ButOH

EtoH

Cyclopropyl ketones (96) have been formed in moderate yield from the esters of 3-hydroxypropylphosphonium salts by treatment with potassium t-b~toxide.~ The ~ acidity and enolization of several /3-ketophosphonium salts have been investigated and discussed in detail.Q7~Q8 0

II R1C-O-CR2R3CH2CH,h3

RlCCH-CR2R3

+ Ph,PO

R1 = Me or Ph

Br-

(96) R2 = H or Ph R3 = H or PhCO

(Cyanomethy1)triphenylphosphonium chloride readily reacts with malonaldehyde acetals gg in pyridine to form phosphorus polymethine dyes (97). Ph3kH2CN

c1-

+

I

(EtO),CHCH( R)CH(OEt),

pyridine NaCIO,

+

Ph3P-C=CHC( R)=CHC=PPh, I I CN CN (97)

The dependence of the 31Pchemical shift of various phosphonium salts on the amount of d,,-pa bonding has been discussed loo(see Chapter 11). PART HI: Phosphorins and Phospholes 1 Phosphorins Preparation.-Undoubtedly the greatest advance in this area of chemistry in the past year has been the discovery of a simple one-step E. E. Schweizer and W. S. Creasy, J. Org. Chem., 1971,36, 2379. T. A. Mastryukova, Kh. A. Suerbaev, P. V. Petrovskii, E. I. Matrosov, and M. I. Kabachnik, Doklady Chem., 1972,202,354. T . A. Mastryukova, I. M. Aladzheva, Kh. A. Suerbaev, E. I. Matrosov, and P. V. Petrovskii, Phosphorus, 1971, 1, 159. A. V. Kazymov and E. B. Sumskaya, J. Gen. Chem. (U.S.S.R.),1971, 41,938. l o o H. Goetz, H. Juds, and F. Marschner, Phosphorus, 1972,1,217. 97

24

Organophosphorus Chemistry

synthesis of phosphabenzene, reported by Ashe.lol The addition of phosphorus tribromide to 1,4-dihydro-1,l-dibutylstannabenzene (98) gave the hydrobromide of phosphabenzene. The free phosphine, a colourless volatile liquid, could be obtained by addition of DBU. Arsabenzene was formed directly in the same way using arsenic trichloride.

Tris(hydroxymethy1)phosphine converted the naphtho[b]pyrylium salt (99) to the corresponding 4-phosphaphenanthrene (100) in the usual way.lo2 Treatment of diphenyl ether with butyl-lithium followed by dichlorophenylphosphine gave 1 O-phenylphenoxaphosphine(101) in low yield.lo3 P11

Ph

Ph (101) 17%

1,l-Disubstituted phosphabenzenes (102) have been prepared by treating pyrylium salts with primary phosphines in pyridine, followed by alcohols or thioalcohols. The yields could be improved by using bis(hydroxymethy1)phosphine instead of the primary phosphine.lo4

p h o p h

BF,-

lol lo2

lo3

lo4

6

aP h \ + R1PH2

I R'

Ph

P 11 R2xH

'P

h 0 . i / /

R2X R'

X = OorS (102) R' = Ph or PhCH, R2 = Ph, Me, or PhCH,

A. J. Ashe, J . Amer. Chem. SOC.,1971, 93, 3293. K. Dimroth and H. Odenwalder, Chem. Ber., 1971, 104,2984. I. Granoth, J. B. Levy, and C. Symmes, J . C. S. Perkin 11, 1972, 697. G. Markl, A. Merz, and H. Rausch, Tetrahedron Letters, 1971, 2989.

Phosphines and Phosphonium Salts

25

Reactions.-The phosphorins (103) were obtained by oxidation of 2,4,6-triphenylphosphorinwith mercuric acetate and an equivalent of alcohol in benzene. If water was added (1 equivalent) and 1.5 equivalents of alcohol used, the compounds (104) were formed.los Deacylation of

/ \

RO 0-

l-acetoxy-l-alkoxy-2,4,6-triphenylphosphorins(103) occurred with base.lo6 Thermal rearrangement of (103) in refluxing dioxan gave (105), an equilibrium reaction which is thought to occur via an intramolecular fourmembered cyclic intermediate. The reaction of the 1,l -bis(dimethylamino)phosphorin (106) with excess methanol in the presence of trifluoroacetic acid produced the methoxyderivative (107) by nucleophilic attack of methanol on the intermediate cation.lo7 105 lo6

lo'

A. Hettche and K. Dimroth, Tetrahedron Letters, 1972, 829. A. Hettche and K. Dimroth, Tetrahedron Letters, 1972, 1045. K. Dimroth, A. Hettche, H. Kanter, and W. Stade, Tetrahedron Letters, 1972, 835.

26

Ph

6 Ph

\

Organophosphorus Chemistry

MeOH

CF,CO,H,

Ph

Me,N

fi

Ph H

Ph H

Ph /p\ Me,N 1 OMe NMe,

/-\

NMe,

Phosphorinylcarboniumtetrafluoroborates were obtained by hydride-ion abstraction from (1 08) with triphenylcarbonium tetrafluoroborate.lo8 The ambidentate character of the carbonium ions was shown by their reactions

i/

Pli

6 Ph

\

0 OMe (110) X = C1, Br, or I -t

'Ph:; NaBH,BF,-,

P hO \

P

h

f---j

/ /

/ /

Me0

CH,

CH,

OMc

Me0

P h O P h / \

M e 0 OMe

OMc

(108)

/ \

(111) lo8

Me0 (109) Y

=

OMe

C N or SCN

K. Dimroth, W. Schafer, and H. H. Pohl, Tetrahedron Letters, 1972, 839.

27

Phosphines and Phosphonium Salts

with n ~ c l e o p h i l e s . Sodium ~~~ borohydride reduction gave the original starting material (108). Cyanide and thiocyanate ions similarly added to give (log), but reaction with halide ions gave the methylene derivatives (110). However, addition of aqueous sodium bicarbonate led to bisphosphorinylmethanes (111). The sequence of the highest-occupied molecular orbitals for phosphorins has been calculated from the photoelectron spectrum of 2,4,6-tri-tbutylphosphorin.l1° The reaction of phosphorins with singlet oxygen has been studied ll1 (see Chapter 10, Section 1).

2 Phospholes A general method of synthesis of phosphole derivatives is illustrated by the preparation of l-phenoxy-3,4-diphenylphospholel-oxide (1 12) by a bromination-debrominationsequence as shown.l12 Br

Further reports on the preparation of phospholes, e.g. (113), by the addition of phosphines to diacetylenes have appeared.ll3#114 Braye and coworkers 113 found that the reaction was best catalysed by concentrated potassium hydroxide or by means of cuprous or mercury salts. Contrary to previous reports the free radical reaction, catalysed by AIBN, also gave good yields. A full account 11*has now been produced of the low inversion barrier of phospholes (114). The energy barriers to inversion of phosphindoles (115) and dibenzophospholes (116) are significantly higher, results interpreted in terms of disruption of stabilization due to phosphole aromaticity in the planar transition state. The site of protonation of 109

l11

11*

114

W. Schafer and K. Dimroth, Tetrahedron Letters, 1972, 843. H. Oehling, W. Schafer, and Armin Schweig, Angew. Chem. Internat. Edn., 1971, 10, 656.

K. Dimroth, A. Chatzidakis, and 0. Schaffer, Angew. Chem. Internat. Edn., 1972, 11, 506.

F. B. Clarke and F. H. Westheimer, J. Amer. Chem. SOC.,1971, 93, 4541. E. H. Braye, I. Caplier, and R. Saussez, Tetrahedron, 1971, 27, 5523. W. Egon, R. Tang, G. Zon, and K. Mislow, J. Amer. Chem. SOC.,1971,93,6205.

Organophosphorus Chemistry

28

1,2,5-triphenylphospholeis the phosphorus atom.115 Some phospholium salts (1 17) are remarkably stable. The anions (118) are formed by the addition of alkali metals to 1 -phenylphospholes. Protonation of the anions gave phosphorusunsubstituted phospholes, reaction with alkyl halides afforded the phospholes (1 19), and subsequently the phosphonium salts (120).

(118) R1 = H or Ph

R'

R'

P h g P h P

I R2

( 1 19)

R: R'X

R'

'

xi\ R2 R 2 ( 120)

The formation of radical-anion intermediates from the reaction of phospholes with alkali metals has been demonstrated by e.s.r. 11' 116

116 117

R. Churchman, D. G . Holah, A. N. Hughes, and B. C. Hin, J . Heterocyclic Chem., 1971, 8, 877. C. Thomson and D. Kilcast, Chem. Comm., 1971, 782. D. Kilcast and C. Thomson, Tetrahedron, 1971, 27, 5705.

2

Quinquecovalent Phosphorus Compounds BY S. TRIPPETT

1 Introduction Interest in stable quinquecovalent phosphorus compounds has shown remarkable growth in the year under review, published work having quadrupled. This is undoubtedly due to a general realization that a knowledge of the factors which affect the stability of such compounds and control the processes of ligand reorganization within them is essential to a proper understanding of the mechanism of substitutions at phosphorus. Variable-temperature n.m.r. studies on stable phosphoranes are giving an increasing amount of data on the relative apicophilicities of groups and on the preference of small-membered rings for the apical-equatorial position, and it should soon be possible to discuss this area of organophosphorus chemistry on a firm semi-quantitative basis.

2 Ligand Reorganization and Structure Several accounts have appeared of the turnstile rotation (TR) process for the reorganization of the ligands of a trigonal bipyramid. As an alternative to the Berry pseudorotation process (BPR), TR offers the prospect of multiple-TR routes which avoid the high-energy trigonal bipyramids which of necessity must be traversed in comparable BPR routes. However, the experimental evidence for TR is still limited to the adamantoid oxyphosphoranes derived from hexafluoroacetone,2and it may be that the possibility of irregular isomerizations has not been entirely eliminated in these cases.3 Until more compelling evidence is forthcoming most workers are using BPR for discussion of their results. Non-empirical * and semi-empirical lo, MO calculations have appeared on the electronic structure and bonding in simple phosphoranes and on the (a) F. Ramirez, S. Pfohl, E. A. Tsolis, J. F. Pilot, C. P. Smith, I. Ugi, D. Marquarding,

P. Gillespie, and P. Hoffmann, Phosphorus, 1971, 1, 1; (b) I. Ugi, D. Marquarding, H. Klusacek, P. Gillespie, and F. Ramirez, Accounts Chem. Res., 1971, 4, 288; (c) P. Gillespie, P. Hoffmann, H. Klusacek, D. Marquarding, S. Pfohl, F. Ramirez, E. A. Tsolis, and I. Ugi, Angew. Chem. Internat. Edn., 1971,10,687; ( d )I. Ugi and F. Ramirez, Chem. in Britain, 1972, 8, 198. ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1972, vol. 3, pp. 39 and 255. See reference l(c) p. 712 for a discussion of this point. A. Rauk, L. C. Allen, and K. Mislow, J. Amer. Chem. Soc., 1972, 94, 3035. (a) J. B. Florey and L. C. Cusachs, J . Amer. Chem. SOC.,1972,94,3040; (6) R. Hoffman, J. M. Howell, and E. L. Muetterties, J. Amer. Chem. Soc., 1972, 94, 3047.

29

30

0rganophospho r us Chemistry

barriers to BPR. They agree with all previous approaches in confirming that the more electronegative substituents will prefer to occupy the apical positions in a trigonal bipyramid. However, other predictions are novel and promise to be of fundamental significance. They can be summarized as follows : ( a ) Electronegative substituents will prefer to occupy the basal positions in a square ~ y r a m i d5 ,b ~as~ will 7r-acceptors 5 b ; n-donors, on the other hand, favour apical These preferences will affect the energy barriers to Berry pseudorotations. (b) In a trigonal bipyramid, orbital overlap from 7r-donors is substantially greater lc,5 b from equatorial than from apical positions. Conversely, orbital overlap is greater for n-acceptors in the apical positions. The overall apicophilicity of a group is therefore a balance between electronegativity and rr-donor or 7r-acceptor proper tie^.^^ This concept has been used independently to explain experimentally derived relative apicophilicities (see below). (c) An equatorial substituent with a single donor orbital will prefer to have that orbital in the equatorial plane.5b Consequently there will be a barrier to rotation round the equatorial bond. This is probably the origin of the slow rotations observed round these bonds in amino- and alkylthiofluorophosphoranes;8 if so the energy barriers found, ranging from 5 to 12 kcal mol-l, reflect the importance of this effect. (d)An overall stabilization of a trigonal bipyramid occurs when all the equatorial or both of the apical positions are occupied by the same type of substituent, lC Computer simulationDof the line broadening of the methyl resonances in the n.m.r. spectra of the phosphoranes (1; R = Me or Ph) down to - 184 "C gave a value for the free energy of activation for pseudorotation between the equivalent structures (la) and (lb) of 4.9-5.1 kcal mol-l. A

knowledge of the barrier to pseudorotation between trigonal bipyramids of identical energies is important in interpreting the barriers observed between non-identical trigonal bipyramids.

'

R. K. Oram and S. Trippett, J. C. S. Chem. Comm., 1972, 554. M. J. C. Hewson, S. C. Peake, and R. Schmutzler, Chem. Comm., 1971, 1454. S . C. Peake and R. Schmutzler, J . Chem. SOC.( A ) , 1970, 1049. C. H. Bushweller, H. S. Bilofsky, E. W. Turnblom, and T. J. Katz, Tetrahedron Letters, 1972, 2401.

Quinquecoualent Phosphorus Compounds

31

Orbital symmetry considerations5 b show that the concerted reactions are symmetry forbidden for apical-equatorial loss or addition, but allowed for apical-apical or equatorial-equatorial. Further kinetic investigations lo of the reactions of phosphites with a-diketones are held to support the previously suggested mechanism in which the first and slow step involves nucleophilic attack of phosphorus on carbonyl carbon. The relative rates of reaction of a series of phosphines with diethyl peroxide to give diethoxyphosphoranes are in the reverse order of those for reaction with ethyl i0dide.l' The differences involved are small but are consistent with a concerted biphilic addition to the peroxide. A group theoretical description of isomerization processes in a trigonal bipyramid has been given.12 3 Acyclic Systems Aminotetrafluorophosphorane has been prepared l3 by amination of the corresponding chloro-compound in the vapour state. Rotation round the PN bond is slow on the n.m.r. timescale at 30°C and analysis of the lH and 19Fn.m.r. spectra of the 16Nisomer shows that in the ground state the hydrogens and apical fluorines are coplanar, as in (2), with strong intramolecular hydrogen-bonding.

Full details have appeared l4 of the preparation of aryloxyfluorophosphoranes (3) according to the general equation

Ar = CeHS or C6F5 R = Me or Ph n = 0, 1, or 2

The lQFn.m.r. spectrum of PhOPPhzFzdid not change down to - 80 "C, lo l1

la

l3

l4

Y. Ogata and M. Yamashita, J. C . S. Perkin ZI, 1972, 493; J. Org. Chem., 1971, 36, 2584; Tetrahedron, 1971, 27, 2725. D. B. Denney, D. Z. Denney, C. D. Hall, and K. L. Marsi, J. Amer. Chem. SOC.,1972, 94, 245.

J. Brocas and M. Gielen, Bull. SOC.chim. belges, 1971, 80, 207. A. H. Cowley and J. R. Schweiger, J . C . S. Chem. Comm., 1972, 560. S. C. Peake, M. Fild, M. J. C. Hewson, and R. Schmutzler, Znorg. Chem., 1971,10,2723.

32

Organophosphorus Chemistry

-

suggesting that rotation round the PO bond is still rapid at this temperature. R,P=CH,

+ HF

-70" C

R,MePF (4)

The fluorophosphoranes (4;R = Me, Bu, or Ph) were obtained15 from the corresponding methylenephosphoranes as shown. Although showing unit molecular weights in non-polar solvents, their i.r. and Raman spectra suggest that they are largely ionic, while the lack of H F and PF coupling in their n.m.r. spectra shows that rapid intermolecular fluorine exchange is occurring. The methoxyphosphorane (5; R = Me) is in rapid equilibrium with the ylide and methanol in non-polar solvents at room temperature, but with the phenoxyphosphorane (5; R = Ph) this equilibration is slow on the n.m.r. timescale under the same conditions.16 Methylmethoxytriphenylphosphorane is covalent in the crystalline state, but its solutions are tinged with the yellow of the ylide. Me,P=CH,

+ ROH

Me,POR (5)

Acyclic phosphoranes containing at least two alkoxy-groups undergo exchange reactions with 1,2- and 1,3-glycols to give phosphoranes containing one or two rings.17 Thus pentaethoxyphosphorane with an equimolar amount of ethylene glycol gave the monocyclic phosphorane (6), whereas with two molar equivalents of glycol the bicyclic phosphorane (7)

was obtained. Other diols used included dZ-butane-2,3-diol,styrene glycol, cis- and trans-cyclohexane-1,2-diol, and propylene glycol. However, in the same reaction butane- 1,4-diol and pentane- 1,5-diol gave tetrahydrofuran and tetrahydropyran, respectively, and this heterocyclic synthesis has been extended l8 to other diols and to aminoalcohols. Thus 2-aminoethanol gave aziridine in 70% yield. The mechanism of the reaction is clearly shown by the formation of the oxide (8) from trans-cyclohexane-l,4-diol. l5

l8

H. Schmidbauer, K.-H. Mitschke, and J. Weidlein, Angew. Chem. Internat. Edit., 1972, 11, 144. H. Schmidbauer and H. Stuhler, Angew. Chem. Internar. Edn., 1972, 11, 145. B. C. Chang, W. E. Conrad, D. B. Denney, D. Z . Denney, R. Edelmann, R. L. Powell, and D. W. White, J. Amer. Chem. SOC.,1971, 93, 4004. D. B. Denney, R. L. Powell, A. Taft, and D. Twitchell, Phosphorus, 1971, 1, 151.

Quinquecovalent Phosphorus Compounds

33

U

The equilibrium between phosphonium methoxide and methoxyphosphorane has been ObservedlO in some cases by 31Pn.m.r. Thus the 31P chemical shift of a solution of the salt (9) in methanol changes from + 14.5 to + 91.7 p.p.m. as the methoxide ion content is increased to 3 molar

equivalents. The equilibration is slow at low temperature and at - 80 "C the separate phosphonium and phosphorane resonances can be seen. Molybdenum hexafluoride has been used 2o for the preparation of difluorophosphoranes from phosphines and of trifluorophosphoranes from chlorophosphines.

4 Four-membered Rings Data on the relative apicophilicities of groups have been obtained6 from a study of the variable-temperature 1°F n.m.r. spectra of the hexafluoroacetone adducts of 1-substituted phosphetans. The pseudorotation that can be followed is that which places the four-membered ring diequatorial, i.e. (10) + (11).21 The results (Table 1) were discussed in terms of apicophilicity being a balance between electronegativity, increase in which

H Me M e H M e

Me

CF, (10) l9 2o

*l

D. W. Allen, B. G. Hutley, and M. T. J. Mellor, J. C. S. Perkin 11, 1972, 63. F. Mathey, and J. Bensoam, Compt. rend., 1972, 274, C, 1095. A. E. Duff, R. K. Oram, and S. Trippett, Chern. Comm., 1971, 1011.

34

Organophosphorus Chemistry

favours occupation of the apical position, and ability to back-bond into phosphorus d-orbitals, increase in which favours occupation of the equatorial positions (see also Section 1).

Table 1 R Ph CH=CMe, AG*/kcalmol-l > 22 19.1

Pri Me NMe, OPh OCH(CF,), H 17.8 16.9 16.2 9 <7 <7 N

The phosphetan (12) with bis(trifluoromethy1) peroxide or bis(trifluor0methyl) disulphide at - 78 "C gave 23 the difluorophosphorane (13). The 31P and lH n.m.r. spectra at - 100 "C show clearly that the phosphorane is a 2.3:l equilibrium mixture of (13a) and (13c), equilibration via the high energy phosphorane (13b) being slow at this temperature. The apicophilicity of fluorine is balancing the increased strain involved in placing the four-membered ring diequatorial. Me

Me

Me

Me

The same phosphetan (12) with the dithieten (14) gavez3 the stabIe 147°C. adduct (15) whose lH n.m.r. did not change from - 50 to The formation of 1,3,2-dithiaphospholens from (14) and tervalent phosphorus compounds is a general reaction; they appear to be less stable than the corresponding 1,3,2-dioxaphospholens. The energy barrier to the pseudorotation (16) + (17) is a function of of the ring size,24being 16-17 kcal mol-1 for n = 3 and about 13 kcal mol-1

+

22 2s !?*

N. J. De'ath, D. 2. Denney, and D. B. Denney, J . C. S. Chem. Comm., 1972, 272. N. J. De'ath and D. B. Denney, J . C. S. Chem. Comm., 1972, 395. D. W. White, N. J. De'ath, D. 2. Denney, and D. B. Denney, Phosphorus, 1971,1, 91.

Q uinqueco valen t Phosphor us Compounds

35

for It = 4. These values compare with 11 kcal mol-1 for the corresponding diethoxy-compounds. An X-ray structure determination has been reported25 for the 1 ,Zoxaphosphetan (1 8), obtained from ethyldiphenylphosphine and hexafluoroacetone. Oxaphosphetans are probably formed from hexafluoroacetone and phosphines containing an a-hydrogen via the ylides (20), formed by proton transfer in the initial 1 : 1 adducts (19).

The exchange of alkoxy-groups when oxyphosphoranes are treated with alcohols is base catalysed.2s When the oxaphosphetan (21) is treated with CD,OD in the presence of tertiary base, CHsOD is liberated before

26

Mazhar-ul-Haque, C. N. Caughlan, F. Ramirez, J. F. Pilot, and C. P. Smith, J . Amer. Chem. SOC.,1971, 93, 5229. F. Ramirez, G. V. Loewengart, E. A. Tsolis, and K. Tasaka, J. Amer. Chem. Sac., 1972, 94, 353 1.

36

Organophosphoriis Chemistry

i

’OMe OMe

(22) CD30-/

- mo]

3 ‘‘

I‘

F3cb “A

1

0C H ( CF3) P’-OMe Me

D3

ir

-(CF,).C H 0 -

f1,. .o

F 3 C j 3.OMe e

l’OCD3 OMe

I’OCD, OCH(CF3 ) z

(CFS),CHOD in spite of the greater acidity of the latter. Nucleophilic attack probably takes place in the equatorial plane, as shown, while the more rapid formation of CH30D is due to the equilibrium between (21) and (22) being in favour of the former because of the greater apicophilicity of the (CF,),CHO group. Me ,NSiMe,

o=c,

NSiMe,

+

Me

R2,PFt5-n)

R1

R1 = Me or Ph F F .. . I / ,P-N R I I ..R ,N -P, I F F

A

O=C,

/N\

,PF(3--n)R274 N R‘

(23)

F F. .. I / P-N R‘I I ..F ,N-P, I R F

-.

-

37

Quinquecovalent Phosphorus Compounds

Details have appeared 27 of the preparation and lgF n.rn.~-.~~? 28 of the diazaphosphetidinones (23). The variable-temperature l9F n.m.r. of the diazadiphosphetidines (24) has been discussed 28 in terms of the equilibrating isomers (24a) and (24b). 5 Five-membered Rings 1,3,2-Dioxaphospholans.-The cyclic phosphonites (25 ; R = Me or Et) reacted with butadiene and with isoprene less rapidly than did (25; R = Ph), but more rapidly than did (25; R = C1 or NCS).29 The phosphite (25; R

(24)

R = PhO) reacted with dienes to give the phosphinate esters (26), doubtless via the phosphoranes.sO For the preparation of 1,3,2-dioxaphospholans by exchange reactions between diethoxyphosphoranes and 1,2-diols, see Section 3 above. The 2:l adducts (28) have been prepared from pyruvate esters and the cyclic esters (27).31

R’,

9, ,PR2 + 0

MeCOC0,R3

(28)

R’= 27

CHMe CH, CHMe I I , I , or CH, ; R2 = OEt or NMe,; R3=Me or Et CH, CHMe I CH,

R. E. Dunmur and R. Schmutzler, J. Chem. SUC.(A). 1971, 1289.

** R. K.

as

Harris, J. R. Woplin, R. E. Dunmur, M. Murray, and R. Schmutzler, Ber. Bunsengeseilschaftphys. Chem., 1972, 76, 44. Zh. L. Evtikhov, N. A. Razumova, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971,

41, 471.

Zh. L. Evtikhov, B. B. Shurukhin, N. A. Razumova, and A. A. Petrov, J. Gen. Chern.

s1

(U.S.S.R.), 1971, 41, 472.

A. N. Pudovik, I. V. Gur’yanova, L. A. Burnaeva, and E. Kh. Karimullina, J. Gen. Chem. (U.S.S.R.),1971, 41, 1995.

38

Organophosphorus Chemistry

1,3,2-Dioxaphospholan-4-ones[ (29) or (31) ] are obtained 32 from a-hydroxy-acids and phosphorus trichloride or the cyclic ethylene esters (30). The betaines (32) are the initial products from a-hydroxy-acids and the phosphoramidite (30; R1 = H, R2 = NEt2).33 The isomers observed by lH n.m.r. in these dioxaphospholan-4-ones seem to be restricted to those due to cis-trans relations among the ring substituents and the P-hydro gen.

H

R3 O\l /O 7 R 4 x P 3 R 1 R' = CI or OAc 0 0' \o (31)

Base-catalysed additions of the phosphoranes (33; X = 0 or NH) to acrylic esters and acrylonitrile have been reported, as well as radical addition of the phosphorane (33; X = 0)to vinyl H

):O ['!)

x o

CH,CH,CO,R

+ CH,=CHCO,R

---+

CH,CH,OR (33; X = 0 )

88

33 34

+

CH,=CHOR

AIBN ~

M. Koenig, A. Munoz, and R. Wolf, Bull. SOC.chim. France, 1971, 4185. M. Koenig, A. Munoz, R. Wolf, and D. Houalla, Bull. SOC.chim. France, 1972, 1413. N. P. Grechkin and G. S. Gubanova, Bull. Acad. Sci., U.S.S.R., 1970, 2637.

Quinquecovalent Phosphorus Compounds

39

1,3,2-Dioxaphospholens.-The phosphoranes (34) and (35) have been fully characterized as quinquec~valent,~~ in contrast to the betaine formed from biacetyl and tris(diethy1amino)phosphine. The bis(trimethylsily1) ether (36) with fluorophosphoranes gave 36 the monocyclic phosphoranes (37), except with tetrafluorophosphoranes and

NEt, (34)

p

R

PF5 when the major products were the bicyclic compounds (38). However, using the bis-t-butyl-substituted ether (39) the monocyclic phosphoranes (40; n = 0 or 1) were obtained as stable distillable l i q ~ i d s . ~At ' - 88 "C the leF n.m.r. of (40; n = 1, R = Me) showed two distinct fluorines, i.e. the pseudorotation which places the two fluorines equatorial is slow on the n.m.r. timescale at this temperature. Although there is no evidence for the presence of PrI1 species in the tetraoxyphosphoranes (41) and (42), the 31P n.m.r. of the closely related (43) showed the presence of the two phosphites (44) and (45).38 No quinquecovalent adducts were obtained from the phosphines Et2PMR3(M = Si and Ge) and b i a ~ e t y l . ~ ~ as se s7

38

a@

I. P. Gozman and 0. A. Raevskii, Bull. Acad. Sci., U.S.S.R.,1971, 1393. G. 0. Doak and R. Schmutzler, J. Chem. SOC.( A ) , 1971, 1295. M. Eisenhut and R. Schmutzler, Chem. Comm., 1971, 1452. R. Burgada and D. Bernard, Compr. rend., 1971,273, C, 164. J. SatgC, C . Couret, and J. EscudiC, J. Organometallic Chem., 1971, 30, C70.

40

Organophosphorus Chemistry H

8:

Me.A.H MeCO

Ar

41

Quinquecovalent Phosphorus Compounds

A full account has appeared40 of the reactions of the benzil-trimethyl phosphite adduct with sulphenyl chlorides. The cyclopropanes (47) are obtained 41 from arylidenemalononitriles and the biacetyl-trimethyl phosphite adduct. The preponderance of the isomer shown is held to be due to the greater stability of the intermediate (46) than of its diastereoisomer. Ph

Ph

There are several reports in the literature of stable quinquecovalent phosphoranes having an hydroxy-group attached to phosphorus, e.g. (48).42 However, in no case is the evidence compelling and they all seem to require reinvestigation. 1,2-Oxaphospholans.-Full details have appeared 4 3 44 ~ of the reactions of the lactone and dione dimers of dimethylketen with a series of tervalent phosphorus esters and amides, and the postulated quinquecovalent intermediate (49) from the lactone dimer has been isolated in one case.46 Of potential mechanistic significance is the preferred migration of exocyclic substituents in the steps corresponding to (49) -+ (50).

+

NMe,

N Me *O 41

4a 43

44

46

Me (50)

(49)

D. N. Harpp and P. Mathiaparanam, J. Org. Chem., 1972, 37, 1367. E. Corre and A. Foucard, Chem. Comm., 1971, 570. F. V. Bagrov and N. A. Razumova, J . Gen. Chem. (U.S.S.R.), 1970,40,2557. W. G. Bentrude, W. D. Johnson, W. A. Khan, and E. R. Witt, J. Org. Chem., 1972 37, 631. W. G. Bentrude, W. D. Johnson, and W. A. Khan, J. Org. Chem., 1972,37, 642. W. G. Bentrude, W. D. Johnson, and W. A. Khan, J . Amer. Chem. SOC.,1972,94,923.

42

Organophosphorus Chemistry

The formation of a stable 1,2-oxaphospholan from the sodium salt of benzoin and triphenylvinylphosphonium bromide has been extended 46 to substituted vinylphosphonium salts, diastereoisomers being obtained in some cases.

1,2-Oxaphospholens.-Among new ap-unsaturated ketones used in the formation of 1 :1 adducts with tervalent phosphorus compounds are dibenzylidenecyclohexanone,47ethyl benzylidenebenzoyla~etate,~~ and the allenic ketones (5 1).49 Hydrogen chloride and the trimethyl phosphite adduct (52) gave the conjugated (53) and non-conjugated (54) isomers in

R

(52; R = P r ' )

HC'I

L

Me,CHCO.CH=CMe.P(O)(OMe),

+

(53)

Me,CHCO-CH,C(:CH,) .P(O)(OMe),

(54)

a ratio of 1 :9. Additional examples have appeared of the use of methyl With the former, vinyl ketone 6o and of ethyl isopropylidenea~etoacetate.~~ and with mesityl oxide, acetyl ethylene phosphite (55) gave 50 spirophosphoranes which were stable under the rather vigorous reaction conditions. The equilibration and the variable-temperature 31Pand lH n.m.r. spectra of the isomeric adducts formed from benzylideneacetylacetone and the In ethylene phosphites (56; R = OMe or NMe,) have been 40

47 48

49 50

5a

E. E. Schweizer and W. S. Creasey, J . Org. Chem., 1971, 36, 2244. B. A. Arbuzov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Doklady Chern., 1971,200,807. B. A. Arbuzov, E. N. Dianova, and V. S. Vinogradova, Bull. Acad. Sci., U.S.S.R., 1970, 2338. G. Buono and G. Peiffer, Tetrahedron Letters, 1972, 149. A. K. Voznesenskaya, N. A. Razumova, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 228. B. A. Arbuzov, E. N. Dianova, and V. S. Vinogradova, Doklady Chem., 1970,195,898. D. Bernard and R. Burgada, Compt. rend., 1972, 274, C , 288.

43

Quinquecoualent Phosphorus Cornpourids

Me

Me

+ R

R

= =

OMe, m.p. 135 "C NMe,, map. 155 "C

each case fractional crystallization gave one pure isomer. Although equilibration of the isomers was slow on the n.m.r. timescale at high temperatures, and there was no evidence of dipolar species, in each case the four signals observed at low temperatures for the four methyls of the dioxaphospholan rings coalesced to give two signals at higher temperatures. The cause of these changes is not clear; they cannot be brought about by normal Berry pseudorotations. The thermally stable compound, m.p. 170-172 "C,formed from the ylide (57) and p-bromobenzaldehyde, has been shown by X-ray analysis 63 to be the dioxyphosphorane (58). Ph,P(OEt)=C(COPh) CH,COPh (57)

+ p-BrC,H,CHO

-

Ph...

I

\

phOf) O 0

I Ph

Yo

H C,H,Br-p (58)

1,3,2-Oxazaphospholans.-The salts (60) obtained 64 from the ethylene phosphites (59) and /3-amino-alcoholsgave the spirophosphoranes (62) on treatment with base, and were re-formed from (62) with carboxylic acids. However, the spirophosphorane (61) was unaffected by benzoic acid and was formed directly in the absence of additional base. a-Amino-acids and the phosphorochloridite (63) in the presence of base gave the phosphoranes (64).55 The variable-temperature lH n.m.r. of the 33p

68 64

66

D. D. Swank, C. N. Caughlan, F. Ramirez, and J. F. Pilot, J. Amer. Chem. Soc., 1971, 93, 5236. R. Burgada, D. Bernard, and C. Laurenco, Compt. rend., 1972, 274, C, 419. A. Munoz, M. Koenig, B. Garrigues, and R. Wolf, Compt. rend., 1972, 274, C, 1413.

44

+

+X ): X

=

CI o r OAc

(59)

HOCHRCH,NH,

-

Organophosphorus Chemistry qI)OCHRCH,&H,

X-

I

(60) ,+I

RCO,H

Base

spirophosphoranes (65; R = Me, But, or OMe) have been explained in terms of p s e u d ~ r o t a t i o n . ~ ~ An exchange reaction between triethoxydiphenylphosphorane and diethanolamine gave 57 the bicyclic phosphorane (66).

1,3,5-Oxazaphospholens.-Phosphites add rapidly to the acylimines (67) to give the 1 :1 adducts (68), which are stable in the absence of moisture but decompose on attempted d i s t i l l a t i ~ n .The ~ ~ 1,3-dipoles (69) formed on thermolysis 59 or photolysis 6o have been trapped with electrophilic olefins and acetylenes and with isocyanides.61 57 58 G9

6o

L. Beslier, M. Sanchez, D. Houalla, and R. Wolf, Bull. SOC.chim. France, 1971, 2563. B. C. Chang, unpublished work quoted in reference 11. K. Burger, J. Fehn, and E. Moll, Chem. Ber., 1971, 104, 1826. K. Burger and J. Fehn, Angew. Chem. Internat. Edn., 1971, 10, 728, 729. K. Burger and J. Fehn, Tetrahedron Letters, 1972, 1263. K. Burger and J. Fehn, Angew. Chem. Internat. Edn., 1972, 11, 47.

45

Quinquecovalent Phosphorus Compounds

(CF,)&=NCOR' (67)

+

.$' P(OR2),

----+

(CF3)2(I,/0 (OR2),

(68)

l+

h or h v

?yR1 +---

R"NC

,N=CR' (CF3)2C (69)

R'

I

+

(R20),P0

R T H =CH RP

R'

H R4

H 'R3

(71) 71%

t

McLi

1

( 7 2 ) - HzO

46

Organophosphorus Chemistry

Miscellaneous.-Additional examples of the cage-like phosphoranes (70) have been obtained,62 including the first penta-alkylphosphorane (70; R1, R2,R3 = Me). The biphenylylenephosphonium salt (73) with methyl-lithium gave63the phosphorane (71), but with (72) gave only the phosphorane (74) and not a six-co-ordinate anion analogous to that formed from the bisbiphenylylene salt and (72). The order of reactivity MeOPCl, > (63) > (EtO)2PCl 9 (MeO),P has been found 64 for addition to isoprene. This diene and the phosphites (75) gave only the phospholens (76).65 If phosphoranes are intermediates in these reactions, then the fate of the aromatic nucleus is of some interest. The phospholens (77) with diethyl peroxide gave isoprene and diethyl phenylphosphoni te, presumably via the phosphorane.ll

0

+ (EtO),

+

---+

Ph

+ PhP(OEt),

(77)

0

F3C

F3C

CF3 CF3

From the multiplicity of its 19F n.m.r. spectrum, it seems unlikely that the compound obtained 66 from hexafluorobut-2-yne and the gold complex MeAuPPh, has the structure (78). 62

64

E. W. Turnblom and T. J. Katz, J . Amer. Chem. Soc., 1971, 93, 4065. E. W. Turnblom and D. Hellwinkel, J . C. S. Chern. Comm., 1972, 404. L. I. Zubtsova, N. A. Razumova, and T. V. Yakovleva, J , Gen. Chern. (U.S.S.R.), 1971, 41, 2450.

66

66

B. A. Arbuzov, V. IS.Krupnov, and A. 0. Vizel, Bull. Acad. Sci., U.S.S.R., 1971, 20 1233. C. M. Mitchell and F. G . A. Stone, J . C. S. Dalton, 1972, 102.

47

Quinquecovalent Phosphorus Compounds

X-Ray analysis has shown6' that although the 31Pchemical shift of the phosphorane (79) is + 66.9p.p.m. and the geometry around the phosphorus is approximately trigonal bipyramidal, the PO bond length is 2.14A. Contributions to the structure by the dipolar species (80) and (81) are suggested. The 2:l adducts formed at low temperature from dimethylketen and phosphites or aminophosphines have now been shown 68 to

Me,C=C=O

3- P X Y Z

EtOAc

Y

R2

M 0 N M ~

R'

R1COCR2=NMe

+ PXYZ

\

/

X+Z Y

6' g8

I. Kawamoto, T. Hata, Y.Kishida, and C. Tamura, Tetrahedron Letters, 1972, 1611. W. G. Bentrude, W. D. Johnson, and W. A. Khan, J . Amer. Chern. Sac., 1972,94,3058.

48

Organophosphorus Chemistry

be 1,3,5-dioxaphospholans (82) and not the previously suggested 6 9 1,3-oxaphospholans. a-Imino-ketones have been condensed 70 with a range of phosphites and related tervalent phosphorus compounds to give the 1,3,2-ox~aphospholens (83). The imino-ketones are less reactive than the corresponding a-diketones. The isolation of the aminotetroxyphosphorane (86) in 50% yield from the reaction of the nitro-compound (84) with an excess of trimethyl phosphite 71 provides evidence for the formation of spirodienyl intermediates, e.g. (85), in deoxygenations of nitro-compounds involving rearrangements. Although acyclic aminophosphines with amidoximes give the oxides (87), cyclic phosphoramidites, e.g. (88), yield isolable phosphoranes (89).72 With \

,PNMe,

+

I

'

NW) R1C(:NOH).NHR2 ---+ RICH \ NHR2 (8 7)

RCONHNH,

69

70

i1 i2

+

(Me,N),P

Reflux

R

' N \

&

I

.H

W. G . Bentrude and W. D. Johnson, J. Amer. Chem. SOC.,1968,90,5924. D. Bernard and R. Burgada, Compt. rend., 1971, 272, C, 2077. J. I. G. Cadogan, D. S. B. Grace, P. K. K. Lim, and B. S. Tait, J. C. S. Chem. Comm., 1972, 520. L. Lopez and J. Barras, Cumpt. rend., 1971, 273, C, 1540.

Quinquecovalent Phosphorus Compounds

49

benzamidoxime, exchange then occurs to give the phosphorane (go), which is also obtainable directly from benzamidoxime and phosphorus trichloride in the presence of triethylamine. The compounds previously obtained from acyl hydrazides and phosphorus trihalides have now been obtained 73 using tris(dimethy1amino)phosphine and shown to be the spirophosphoranes (91). The oxathiaphospholans (92) are less reactive towards a-diketones than are the corresponding dioxapho~pholans.~~ The phosphites (93) and (94) exist as such 74 and do not give the trioxythiopho~phoranes.~~

6 Six-co-ordinate Species The preparation of the salt (95) has been improved 76 by using phosphorus trichloride at room temperature instead of the pentachloride at - 70 "C. The spirophosphorane (96) with ethylene glycol and sodium methoxide gave the tris(ethy1enedioxy)phosphate (97).77 Attempts to prepare the six-membered-ring analogue failed. X-Ray analysis of the salt (98) confirmed the octahedral arrangement of oxygens around phosphorus. 78

74 76

'13 77

A. Schmidpeter and J. Luber, Angew. Chem. Internat. Edn., 1972, 11, 306. D. Bernard, P. Savignac, and R. Burgada, Bull. Soc. chim. France, 1972, 1657. P. M. Zavlin, E. R. Rodnyanskaya, A. I. D'yakonov, and V. M. Al'bitskaya, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1883. R. Rothius, T. K. J. Luderer, and H. M. Buck, Rec. Trau. chim., 1972, 91, 836. €3 C. Chang, D. B. Denney, R. L. Powell, and D. W. White, Chem. Comm., 1971, 1070.

H. R. Allcock and E. C. Bissell, J. C. S. Chem. Comm.,1972, 676.

50

Organophosphorus Chemistry

0-P

+

HOCH,CH,OH

NaoMe

___j

Na' PE]]3

(97) alp +89 p.p.m.

3

Halogenophosphines and Related Compounds BY J. A. MILLER

1 Halogenophosphines The number of papers in the field of halogenophosphines has risen dramatically this year, and this has necessitated the omission of a significant number of papers from this survey. In general these have reported isolated reactions of a routine nature. There has been almost no new preparative work described this year, and the section has accordingly been divided into sub-sections on physical aspects and on chemical reactions. Physical Aspects.-Interest continues in the question of the participation of d-orbitals in the bonding in phosphorus trihalides and their oxides. A number of ab initio calculations have been applied to phosphorus trihalide~,l-~and there is general agreement that the inclusion of d-orbitals in the basis set gives a better bonding picture in the fluoride 1, 3, * and although in the higher halides the d-orbital contribution to the phosphorus-halogen bonds is very small. The oxyhalides have considerable d-orbital participation in the phosphoryl b0nd.l~ Recent comment by CouIson,6that the inclusion of d-orbitals in the basis set for MO studies need not necessarily be of chemical significance, even when improved wave-functions result, has been extended by Ratner and Sabin,6 who suggest that symmetry considerations of the state in question could be used to give some indication of the desirability of including d-orbitals. Photoelectron spectroscopy has been used to measure the binding energy of phosphorus trifluoride and trichloride,* and their oxides,7,* and the results are in good agreement with ab initio calculations. E.s.r. studies of phosphorus trichloride and pentachloride, and n.q.r. studies lo of 35CI nuclei in phosphorus trichloride and a series of substituted 2t

e-

A. Serafini, J.-F. Labarre, A. Veillard, and G. Vinot, Chem. Comm., 1971, 996. I. H. Hillier and V. R. Saunders, J . C. S. Dalton, 1972, 21. M. F. Guest, I. H. Hillier, and V. R. Saunders, J . C. S. Faruduy 11, 1972, 68, 114. M. F. Guest, I. H. Hillier, and V. R. Saunders, J. C. S. Faraduy 11, 1972, 68, 867. C. A. Coulson, Nature, 1969, 221, 1106. M. A. Ratner and J. R. Sabin, J. Arner. Chem. SOC.,1971, 93, 3542. P. J. Bassett and D. R. Lloyd, J. C. S. Dalton, 1972, 248. M. Barber, J. A. Connor, M. F. Guest, I. H. Hillier, andV. R. Saunders, Chem. Comm., 1971, 943.

lo

A. Begum and M. C. R. Symons, J. Chem. SOC.(A), 1971,2065. J. K. B. Bishop, W. R. Cullen, and M. L. C. Gerry, Cunud. J. Chem., 1971, 49, 3913.

51

52

Organophosphorus Chemistry

derivatives, have been published. Infrared and Raman spectra of various derivatives of phosphorus trichloride l1, l2 and oxychloride l3 have also appeared. A rationalization, based on Ramsay's equation, has appeared for the 'anomalous' order of 31Pn.m.r. shifts of the phosphorus trihalides.la The halogenophosphine (1) has been observed to show separate N-methyl and O-methyl absorptions in (31P-decoupled) lH n.m.r. spectra run at ( MeONMe),PCI

H,N P F,

(1)

(2)

low temperatures,16 and this has been interpreted as resulting from restricted rotation about the phosphorus-nitrogen bond. Aminodifluorophosphine (2) has a very short phosphorus-nitrogen bond, and the nitrogen is planar.16 At low temperatures the hydrogens are equivalent, possibly owing to rotation about the phosphorus-nitrogen bond.ls Reactions.--NucZeophiZic Attack by Phosphorus. Alkyldichlorophosphines (3) undergo a mild Arbusov reaction with acid chlorides to give

R'PCI,

R'

+ R2COCl

(3) Me or Et

i, A ii, R30,-i t

0 II R1PCOR2

I

0

~

3

(4)

adducts which yield phosphinates (4) on treatment with alcoholic a1kali.l' Details have appeared of the reaction of chlorodiphenylphosphine ( 5 ) with a number of alkyl benzoates (6).18 The enhanced rate of (6; R = CN) over (6; R = H) was used as evidence for the nucleophilic role of the phosphine ( 5 ) in reactions which lead to two sets of products, as illustrated in Scheme 1. Attack at the carbonyl group is not observed with the ester (6; R = OMe), and an unusual cleavage of the methoxygroup occurs. Chlorine and bromine both form phosphorane adducts with the difluorophosphines (7), and 19F and lH n.m.r. data of the phosphoranes have been discussed (see Section 2, p. 63). l1 l2

rA l4 l5 l6

l7

lD

N. Fritzowsky, A. Lentz, and J. Goubeau, 2. anorg. Chem., 1971, 386,67. N . Fritzowsky, A. Lentz, and J. Goubeau, 2. anorg. Chem., 1971, 386,203. D. Kottgen, H. Stoll, A. Lentz, R. Pantzer, and J. Goubeau, Z . anorg. Chem., 1971, 385, 56. L. Phillips and V. Wray, J. C . S. Perkin II. 1972, 214. A. Hung, and J. W. Gilje, J. C . S. Chem. Comm., 1972, 662. A. H. Brittain, J. E. Smith, P. L. Lee, K. Cohn, and R. H. Schwendemann, J . Arner. Chem. SOC.,1971,93, 6772. S. Kh. Nurtdinov, N. M. Ismagilova, T. V. Zykova, R. A. Salakhutdinov, V. S. Tsivunin, and G. Kh. Kamai, Zhur. obshchei Khim., 1971, 41, 2486. S. T. McNeilly and J. A. Miller, J. Chem. SOC.( C ) , 1971, 3007. G . I. Drozd, M. A. Sokal'skii, and S. Z . Ivin, Zhur. obshchei Khim., 1970, 40, 701.

Halogenophosphines and Related Compounds

53

A R' = OMc

Scheme 1 RPFz

R

=

+ X2 X

(7) Me or Ph

RPFzX2 = Cl or Br

Electrophilic Attack by Phosphorus. A detailed discussion has appeared of the displacement reactions of 1-chloro-2,2,3,4,4-pentamethylphosphetan (8) and its oxide and sulphide.20 The chloride (8) always undergoes inversion as a result of substitution at phosphorus, and this is rationalized on the basis of a transition state (9) in which the entering nucleophile (Nu) and the chloride leaving-group occupy apical sites. Although a pathway via (9)

(9)

+ c1-

results in a considerable increase in ring-strain, over (8), alternative transition states are presumably even less favoured, owing to the necessary equatorial placement of at least one electronegative group [see (69), in Section 2, p. 651. A series of papers on the reactions of chlorodimethylphosphine (10a) or fluorodimethylphosphine (1Ob) with various nucleophiles has been published 21-24 and a summary is presented in Scheme 2. The low-temperature reactions of (loa) with methanol allowed the isolation of an intermediate salt (ll).23 The most complex reaction studied is that between (10a) and the oxide (12), in which attack at the phosphorus of (loa) by the oxygen of (12) is observed.22 ao 21 22

23 24

J. R. Corfield, R. K. Okram, D. J. M. Smith, and S. Trippett,J. C. S. Perkin I, 1972,713. F. Seel and K.-D. Velleman, Chem. Ber., 1971, 104, 2967. F. Seel and K.-D. Velleman, Chem. Ber., 1971, 104, 2972. F. Seel and K.-D. Velleman, Chem. Ber., 1972, 105, 406. F. Seel, W. Gombler, and K.-D. Velleman, Annalen, 1972, 756, 181.

3

54

Organophosphorus Chemistry

lA+

Me,PX (a) X = C1 (b)X = F

(10a)

[ Me,PHOMe]+ Cl -

Me,PZMe

-

Me,P(O)H

+ Me,PF,H

(10) Me,PPMe, Me,PCl

+ Me,P(O)E1

Me,P(O)CI

--+

+ Me,P(O)H

H Mc,POPMe,

0

--+ Mc,PH

Me,P(O)OH Me,P( 0)Cl

II + Me,PCI

+ Me,PCI Me,PH

Simple displacement reactions leading to the cyanides (13),25 and to the phosphinothioites (14) 26 and (15) 27 have been described.

X I R-PSCH,CH=CH, (14)

Br I Et PSR (15)

The reactions of phosphorus tri-iodide with ethers to give complex intermediates (1 6), which decompose to give tetraiododiphosphine and iodine, are controlled by the effect of steric and electronic factors in the ether upon the equilibria shown in Scheme 3.28 Ring-opening reactions 25 26

27

28

C. E. Jones and K. J. Coskran, Inorg. Chern., 1971, 10, 1536. N. I. Rizpolozhenskii, V. D. Akamsin, and R. M. Eliseenkova, Izvest. Akad. Nuuk S.S.S.R., Ser. khim., 1971, 198. A. M. Potapov, E. A. Krasil'nikova, and A. I. Razumov, Zhur. obshchei Khirn., 1970, 40, 566. N. G. Feshchenko, Zh. K. Gorbatemko, and A. V. Kirsanov, Zhur. obshchei Khim., 1971, 41, 551.

Halogenoph osphines and Related Compounds K,O

+ -

+ PI3

R,OI PI,

55

L

+ P,I,

R,O

iI,

(16) Scheme 3

of oxetans with halogenophosphines continue to show interesting structurereactivity effects. Thus 2-methyloxetan (17) with dichloro(pheny1)phosphine ring-opens predominantly at the primary carbon to give (18a) in 90%yield, whereas dichloro(NN-diethy1amino)phosphine gives 75% of (19b), by cleavage of the secondary carbon-oxygen bond of (17) (Scheme 4).29

To v

CI,PR

C1 Me I I R POC HCH,CH,CI (a) R = Ph (90%) (b) R = NEt, (25%) (c) R = CI (100%)

/'

\

(17)

Me I R P OCH2CH,CHC1

I

(a) R (b) R

Scheme 4

Ph (10%) NEt, (75%)

= =

(19)

Phosphorus trichloride is known to give only (18c) in its reaction with (17).30 With the epoxide (20) this trend is reversed (Scheme S), in that CI Me I I RPOCH,CHCl (a) R = CI (b) R = Ph (c) R = NEt,

RPCll

&< Me (20)

(21) CI Me I I R P 0CH,C HC I

(a) R

=

NEt,

(22) Scheme 5 2s 9o

0. N. Nuretdinova, L. Z . Nikonova, and V. V. Pomazanov, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 2225. B. A. Arbusov, L. Z . Nikonova, 0. N . Nuretdinova, and V. V. Pomazanov, Izuest. Akad. Nauk. S.S.S.R.,Ser. khim., 1970, 1426.

56

Organophosphorus Chemistry

phosphorus trichloride 31 and its phenyl analogue 29 cleave the secondary carbon-oxygen bond to give (21a, b), whereas the aminophosphine 30 gives comparable amounts of (21c) and (22a). At face value these results are difficult to rationalize, and it may be that some experimental factor, such as presence or absence of hydrogen chloride, plays an important role. Analogous studies with ethylene phosphorochloridite show that (1 7) 33 and (20) 32 react in the same mode (Scheme 6), giving primary alkyl chloride products !

Scheme 6

Another controversial aspect of ether-halogenop hosphine chemistry is the reactions of acetals or orthoformates with halogenophosphines. Russian workers have shown that the amide (23a) reacts sluggishly with orthoesters and not at all with acetals, whereas the dihalogenophosphine (23b) reacts vigorously with both types of compound (Scheme 7).34 These

Et

/ L(

R 6 ‘CH(OEt), C1- +KbCH(OEt), II bEt 0

+

Eta

I

RPOEt (24)

+ EtCl + HC0,Et

Scheme 7

31

32

33 34

N. I. Shuikin and I. F. Bel’skii, Zhur. obshchei Khim., 1959, 29, 2973. A. N. Pudovik, E. M. Faizullin, and V. P. Zhukov, Zhur. obshchei Khim., 1966, 36,310. 0. N. Nuretdinov, B. A. Arbuzov, and L. Z. Nikonova, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 2086. V. S. Tsivunin, L. N. Krutskii, M. Ernazarov, and G. Kh. Kamai, Zhur. obshchei Khim., 1970, 40,2560.

Halog enophosphines and Related Comp orinds

57

results imply that the initial role of the halogenophosphines is electrophilic, although in a previous study of these reactions, using various halogenophosphines, it was concluded that the phosphorus acts as a n ~ c l e o p h i l e . ~ ~ The isolation of exchange products (24) from a number of these reactions 35 may be rationalized on either basis, as outlined for triethyl orthoformate. Treatment of santonin (25) and derivatives with phosphorus trichloride or tribromide in the presence of acetic acid yields (Scheme 8) complex

CI

;C.r:-: +cl acetates

o

+

0

Scheme 8

mixtures of products in which the ketonic group has been removed, presumably after interaction of the oxygen with the t r i h a l i d e ~ . ~ ~ A rationalization of the reactions between /I-keto-alcohols and halogenophosphines has been presented by a Russian In particular, the reaction between dichloro(pheny1)phosphine(26) and diacetone alcohol to give the oxide (27) has been shown to occur in stages (Scheme 9), and physical and chemical evidence has been presented for the initial formation of mesityl oxide (28) and the acid (29), followed by the addition product (30).37 A less detailed study of the analogous reaction of chlorodiphenylphosphine ( 5 ) with diacetone alcohol has also been published.3s It has been suggested that the related reactions of saturated ketones with halogenophosphines have a similar pathway, and that the initial function of the halogenophosphine is to generate (3 1) by an aldol-type c o n d e n ~ a t i o n . ~ ~ 36 38

37 38 s9

W. Dietsche, Annalen, 1968, 712, 21. T. B. H. McMurray and D. F. Rane, J . Chem. SOC.(C), 1971, 3850. B. A. Arbuzov, N. I. Rizpolozhenskii, A. 0. Vizel, K. H. Ivanovskaya, F. S. Mukhamentov, and E. I. Gol’dfarb, Zzvest. Akad. Nuuk S.S.S.R., Ser. khim., 1971, 117. F. S. Mukhametov, N. I. Rizpolozhenskii, and E. I. Gol’dfarb, Zzvest. Akad. Nuuk S.S.S.R., Ser. khim.,1971, 2221. S. Kh. Nurtdinov, R. S. Khairullin, T. V. Burmakina, T. V. Zykova, R. Salakhutdinov, V. S. Tsivunin, and G. Kh. Kamai, Zhur. obshchei Khim., 1971, 41, 1685.

58

Organophosphorus Chemistry PhPCI,

+

OH I Mc,CCH,COMe

0 Me

II I PhP-CCH,COMe I

(28) t--

I

0

--+

II PhpH

11 PhPH I

0

OH PhzPCl

I

+ Me,C=CHCOMe

+ Me,CCH,COMe

--+

II

Ph2PCMe,CH,COMe

The usual product, after pyrolysis, is a 1,2-0xaphospholen 2-oxide (32), although an alcoholic work-up yields an acyclic phosphinate (33) (Scheme 10). Just in case these advances in our current mechanistic interpretation of these reactions (cf. ref. 40) leads to complacency, a further Russian paper has described the reactions of acetone and other simple ketones with chlorodiphenylphosphine or chlor~diethylphosphine.~~ These yield the a-chloroalkylphosphine oxide (34), or the derived oxide (39, and not the oxide (36), which is known42 to be formed from mesityl oxide (28) and chlor odiethylphosphine. a-Halogenoalkylphosphine oxides are generally produced when aldehydes are heated with a wide range of halogenoph~sphines,~~ and the formation of such an adduct from a ketone is a novel result. 40

41 42

43

J. A. Miller in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical

Reports), The Chemical Society, 1972, vol. 3, pp. 44-45. S. Kh. Nurtdinov, R. S. Khairullin, T. V. Zykova, V. S. Tsivunin, and G. Kh. Kamai, Zhur. obshchei Khim., 1971, 41, 2158. T. V. Zykova, G. Kh. Nurtdinov, and G . Kh. Kamai, Zhur. obshchei Khim., 1967, 37, 692. K. Sasse in ‘Organische Phosphorverbindung, Methoden der Organischen Chemie’, G . Thieme Verlag, Stuttgart, 1963, vol. 12 (l), pp. 155, 403.

Halogenophosphines and Related Compounds 0

R'PCI,

59 CI Me

II + MeCCH2R2

I

I

R1POCCHR2COMe I CH2R2

(31)

:2$pMe A

0 Me

R1PCCHR2COMe II I

I \

R2 Me CH2R2

I

CI CH2R2

(32) A

~

3

0

~

0 Me II I R1PCCHR2COMe

I \ R 3 0 CH2R2 (33)

Scheme 10 0

c1

II I

i'

R2PCI

+

Me,C=O

Et2PCMe,

\ 7

,CH2 PhZPC, Me

(35)

0

Et,PCI

+ Me,C=CHCOMe (28)

___f

I1 Et,PCMe,CH,COMe (36)

A number of aromatic substitution reactions of chlorophosphines have been reported. 1,3,5-Tri-t-butylbenzene gives the phosphinic chloride (37) 44 on treatment with aluminium trichloride, and not the phosphinous chloride (38).45 A simplified preparation of (39) has been de~cribed.*~ 44

4b 46

M.Yoshifuji, R. Okazaki, and N. Inamoto, J. C. S. Perkin I, 1972, 559. A. G . Cook, J . Org. Chem., 1965, 30, 1262. I. Granoth, J. B. Levy, and C. Symmes, J . C. S. Perkin I& 1972, 697.

60

Organophosphorus Chemistry

o=P-Cl t PCI

I

I' I1 (30)

Biphilic Reactions with Dienes and with Unsaturated Curbonyl Compounds. The Diels-Alder reactions of the a/3-unsaturated lactone (40) have been de~cribed.~'The lactone is prepared by treatment of chloromethyldichlorophosphine (41) with propiolic acid and then hot acetic 0

Rates:

x

=

=

Cll Et,

EtO\ EtOl

EtS\

' EtS(

anhydride.47 The ease of addition of halogenophosphines to 1,3-dienes is found to decrease in the sequence outlined for buta-l,3-diene (42).48 Miscellaneous. Boron tribromide treatment of dichloro(pheny1)Phenyl radicals and phosphine (26) gives the dibromide quantitati~ely.~~ 47

O8 49

V. K. Khairullin, G . V. Dmitrieva, and A. N. Pudovik, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 1254. L. I. Zubstova, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1971, 41, 2428. P. M. Druce and M. F. Lappert, J. Chetn. SOC.( A ) , 1971, 3595.

61

Halogenophosphines and Related Compounds PhPCI,

+ BBr,

----+

PhPBr,

(26)

t-butyl radicals react with phosphorus trichloride to give dichloroof olefins in the presence of phosphorus p h o s p h i n e ~ . ~Radiolysis ~ trichloride gives the dichlorophosphines (43).61The oxidative addition of phosphorus trichloride to vinyl chloride has been shown to yield a mixture of the phosphate (44) and the phosphonate (45),62 and not a mixture of (45)

R'CH=CHR2

+

c1 PCI3

60Co

1

R'CH=CHR2PCI, (43a)

+

CI 1 R2CH=CHR1PCl, (43b)

CH2=CHCI

+

y

0

0

II CI,PCHCICH,Cl (45)

+

II Cl,POCHClCH2CI (44)

PCI, CI,PCH2CHCl, (46)

and (46).53 Bis(trifluoromethy1)fluorophosphine (47) is oxidized to the corresponding oxide with nitric It is likely that the reaction of bis(chloromethy1)chlorophosphine with benzaldehyde in wet dioxan to produce the oxide (48) involves the initial hydrolysis of the phosphine, to give (49), which adds to benzaldehyde (Scheme 1l).55

b1

63 s4

6s

L. Dulog, F. Nierlich, and A. Verhelst, Chem. Ber., 1972, 105, 1971. P. A. Zagorets, A. G . Shostenko, and A. M. Dodonov, Zhur. obshchei Khim., 1971'41,

2171.

C. B. C. Boyce and S. B. Webb, J. Chem. SOC.( C ) , 1971, 3987. W. M. Daniewski, M. Gordon, and C. E. Griffin, J. Org. Chem., 1966,31, 2083. R. C. Dobbie, J. Chem. SOC.( A ) , 1971,2894. N. I. D'yakonova, E. Kh, Mukhametzyanova, and I. M. Shermergorn, Zhur. obshchei Khim., 1971, 41, 2203.

62

I Organophosphorus Chemistry

";1

(CICH,),PCI

0 OH II I (CICH,),PCHPh

wet

+ PhCH=O

dioxan

(48)

(CICH,),PH 0 It

+

HCI

(49)

PhCH=O

Scheme 11

2 Halogenophosphoranes new routes to the relatively rare Preparation and Structure.-Two tetra-alkylfluorophosphoranes (50) from salt-free ylides have been r e p ~ r t e d .These ~ ~ phosphoranes all have considerable 'fluoride' character (no HCPF coupling), although the tributyl derivative (50; R = Bu) is quite stable and definitely monomeric. Difluorophosphorane (5 1) has been prepared from excess hydrogen fluoride and diphosphine, and found to disproportionate readily to trifluorophosphorane (52).57 The infrared symmetry, which is accounted for by a spectrum of (51) indicates HF

R3P=CHZ ---+

R,P(F)Me

HF

f------

R,P=CHSiMe3

(50)

(PHZ),

+ HF

PHZF

+

PH3.

H2PF3 + PH3

H3PFZ

(52)

(51)

RPF2

+ XZ

-----+ RPFzXz

R

X

PF,

+ FCI

+ HF

> 0°C

=

Ph or Me Br or C1

-

196°C

=

RPF, (54)

PCIF4 (55)

56

H. Schmidbaur, K.-H. Mitschke, and J. Weidlein, Angew. Chem. Internat. Edn., 1972, 11, 144.

57

F. See1 and K. Velleman, 2. anorg. Chem., 1971, 385, 123.

63

Halogenophosphines and Related Compounds

trigonal-bipyramidal structure, with axial fluorines. The addition of chlorine or bromine to difluorophosphines yields the mixed halogenophosphoranes (53), but these disproportionate readily to give (54).1° A related reaction leads to improved yields of chlorotetrafluorophosphine ( 5 3 , provided the vacuum temperature is kept very low.68 Perfluoro-t-butyl hypochlorite has been used to prepare the phosphoranes (56),6Din which the fluorines are equivalent (from n.m.r.) at room temperature. The exchange with aryloxysilanes to give (57) appears to be general and quantitative.60 Detailed l9F and 31Pn.m.r. data on (57) have been

RnPF5-,

I::::&

+

Rn I ArOSiMe3 * (ArO),-,PF, (57) 11 = 0, 1, or 2

+ RPF4

/m

J O T f\

0 (58)

presented, and earlier work 61 in this area questioned.60 Related reactions have been used to prepare the phosphoranes (58), and the variabletemperature n.m.r. spectra analysed.62 Aminotetrafluorophosphorane (59) has been prepared from ammonia, and a detailed analysis of the n.m.r. data (lH, I9F, and 31P)indicates that it has a trigonal-bipyramidal structure, in which the equatorial nitrogen has a planar config~ration.~~ The axial fluorines (JPF760 Hz) are chemically equivalent, but show different coupling to the hydrogens, while the equatorial fluorines (Jpp 936 Hz) are equivalent in both respects. This has been interpreted on the basis of the amino-hydrogens lying in an axial plane, as in (59), with resultant strong hydrogen-bonding to the axial fluorines. Variable-temperature n.m.r. studies have revealed a high barrier to rotation F

Me,NPF4

W. B. Fox, D. E. Young, R. Foester, and K. Cohn, Znorg. Nuclear Chem. Letters, 1971, 7 , 861. D. E. Young and W. B. Fox, Inorg. Nuclear Chem. Letters, 1971, 7 , 1033. Bo S. C. Peake, M. Fild, M. J. C. Hewson, and R. Schmutzler, Znorg. Chem., 1971,10,2723. R. A. Mitsch, J. Amer. Chem. SOC.,1967, 89, 6297. 6 2 M. Eisenhut and R. Schmutzler, Chem. Comm., 1971, 1452. 83 A. H. Cowley and J. R. Schweiger, J . C. S. Chem. Comm., 1972, 560.

64

Organophosphorus Chemistry

[above 15 kcal mol-l, compared with 9 kcal mol-1 for the dimethylaminoanalogue (60)] 64 which has been ascribed to this intramolecular hydrogenbonding.63 N-Methylaminotetrafluorophosphorane (61) has now been prepared by the silane route, and found to give three 19F resonances at - 80 "C, presumably owing to hindered rotation.65 A similar route to the piperidyl derivatives (62) has been described, and the dependence of the non-equivalence of the fluorines upon the position of the methyl group Me,SiNHMe -t PF,

-

SiMe,

r7

X

N-I'FZXZ

W

+

+

Me,SiF

SbF3

(61)

-

Fbi.-,L,PPh, (62) IZ

-1 SbF3

=

0, 1, or 2

n N-PF,

X

W

(63) X

PhN=P(NEt,)Cl,

MeNHPF,

A

=

CH, or 0

Et,NPF.j

(64)

has been rationalized on the same basis.66 Unsubstituted piperidyl- and morpholino-phosphoranes (63) have been prepared by the antimony trifluoride exchange and the same reagent has been used in a more unusual exchange involving the iminophosphorane (64).68 An elegant and stimulating MO analysis of the problems of bonding and structure in phosphoranes has appeared.69 Of particular relevance to the current topic is a discussion of the interactions of the lone pairs of donor substituents with the orbitals on phosphorus. The authors conclude that donor substituents will prefer equatorial sites (except where electronegativity becomes the dominating influence, as with fluorine), and moreover, that the highest occupied donor orbital will prefer to lie in the equatorial plane of the phosphorane, rather than in the axial plane, i.e. (65) is preferred over (66). Although only limited experimental data are available, it would appear that these predictions are fully supported, e.g. the preferred conformation of (67) 7 0 and the features of the phosphoranes (59) and (61), 64 66 66

67

68 69

70

G . M. Whitesides and H. L. Mitchell, J. Amer. Chem. SOC.,1969, 91, 5384. J. S. Harman and D . W. A. Sharp, Znorg. Chem., 1971, 10, 1538. M. J. C. Hewson, S. C. Peake, and R. Schmutzler, Chem. Comm., 1971, 1454. G. I. Drozd, M. A. Sokal'skii, 0. G. Strukov, and S. Z. Ivin, Zhur. obshchei Khim., 1970,40, 2396. M . Bermann and J. R. Van Wazer, Angew. Chem. Internat. Edn., 1971, 10, 733. R . Hoffmann, J. M. Howell, and E. L. Muetterties, J. Amer. Chem. SOC.,1972,94,3047. S. C. Peake and R. Schmutzler, J . Chern. Soc. ( A ) , 1970, 1049.

65

Halogenophosphines and Related Compounds

i65)

(47)

(66)

discussed above. Thus the hindered rotation observed in the aminophosphoranes can be explained on the basis of orbital interactions, and it remains to be seen how important any hydrogen-bonding interactions are in relation to this. Bis(trifluoromethy1) peroxide and disulphide have been used in a novel preparation of the difluorophosphoranes (68) from tertiary p h o ~ p h i n e s . ~ ~ The phosphetan derivative (69), prepared by this route, has been shown to exist as a mixture of two isomers at -1OO"C, one of which has a (CF3X)z

+

R3P

X

=

OorS

II =

R,PF, (48)

1, 2, or 3

diequatorial heterocyclic ring.71 Boron trifluoride catalyses the exchange of ligands in the phosphorane (70).72 Reactions.-An intermediate (7 1) has been isolated from the bromination of alcohols using triphenylphosphine dibromide in dimethylformamide (Scheme 12).73 This implies that these reactions are closely related to the Vilsmeier reaction, and further evidence for this view comes from the isolation of a formylated product (72) from the analogous reaction of cholest-5-ene-3/3,4/3-diol(73).74 The other product (74) appears to be the result of an enol-bromination of the 3-ket0ne.~~Two related reactions which substantiate this are the mild reaction between pentane-2,4-dione and triphenylphosphine dibromide in DMF, to give (75),75and the formation of l-chlorocyclohex-l-ene (76) from cyclohexanone and a solution of 71 72

73 14

76

N. J. De'ath, D. Z. Denney, and D. €3. Denney, J. C. S . Chem. Comm., 1972, 272. H. Binder, 2. anorg. Chem., 1971, 384, 193. M. E. Herr and R. A. Johnson, J. Org. Chem., 1972, 37, 310. J. Dahl, and R. Stevenson, and N. S. Bhacca, J . Org. Chem., 1971, 36, 3243. J. Carnduff, J. Larkin, J. A. Miller, D. C. Nonhebel, B. R. Stockdale, and H. C. S. Wood. J . C. S . Perkin I, 1972, 692.

66

+

Me,NCH=O

+ Me,N=CHOR

Organophosphorus Chemistry +

Ph,PBr,

+

Me,N=CHOPPh,Br

RoHll

t--- Me,N-yHOPPh,Br

Ph,P=O

OR

@ MeNCOPh

OR =

o,H , .

-

Scheme 12

triphenylphosphine in carbon tetra~hloride.'~Thus the conversion of ketones into halogeno-olefins appears to be a promising synthetic reaction of halogenophosphoranes, or their phosphonium relatives, although

+

I

OH

(73)

0 0 I1 II MeCCH,CMe

+

ox

Ph,P-CCI, I1 = 3

(76)

76

DMF

Ph,PBr,

O H C W (72)

0 II MeCCH=C(Br)Me (75)

0 II

/c\

CH,

'(CH,),,

CH,

)

2\

Ph,P-CCI, n = 2

'

6

N. S. Isaacs and D. Kirkpatrick, J. C. S. Chem. Comm., 1972, 443.

(77)

67

Halogenophosphines and Related Compounds

competing pathways clearly exist, as in the reaction of cyclopentanone to give (77).76 The formation of equal amounts of methyl chloride and (78) from phosphorus pentachloride and bis(hydroxymethy1)phosphinic acid has been rationalized (Scheme 13) in terms of the intermediate methyl ester (79).77 0 II (HOCH2)POH

0 II ClCH2PC12

+ PCl,

-

OH I CliPOP-CH2OH / \ O-CH2

+ HCI

1 + CH3Cl

0 II

t---C14P0P0CH3 I

(78) Scheme 13

CH20H (79)

A slightly modified version of this rationalization is presented below. Diols can be converted into oxirans via the corresponding acetals, which fragment via the orthoester derivatives (80) on treatment with phosphorus pentachloride (Scheme 14).78 The sequence is primarily of interest because

Scheme 14

of its stereospecificity, since the final oxiran has the same absolute configuration at carbon as the initial diol, in appropriate cases. Ethers and certain sulphides are cleaved by triphenylphosphine dibromide to give alkyl bromides (Scheme 15), although the reaction is not general 77

Yu. V. Nazarov, A. A. Muslinkin, and V. F. Zmeltukhin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 1806. M. S. Newman and C. H. Chen, J. Amer. Chem. SOC.,1972,94,2149.

Organophosphorus Chemistry

68

R10R2

+

Ph,PBr2 - R2Br

+

+

RlBr

Ph3P=0

Scheme 15

for epoxides, as shown by the reactions yielding (81) and (82), and (83).7s Alkyl iodides result from a similar reaction of the phosphorane (84) with alcohols or ethers such as tetrahydrofuran.*O Further examples of the preparation of vinylphosphonate derivatives from ethers and phosphorus Ph3PBr2 +

0 0--+

i-

+

OPPh3

aBr

Br Br

Ph,PBr, 4-

Me

4Me-

CI (88) 79

A. G. Anderson and F. J. Freenor, J. Org. Chem., 1972, 37, 626. N. G. Feshchenko, I. K. Mazepa, S. I. Shila, and A. V. Kirsanov, Zhur. obshchei Khim., 1971, 41,2375.

Halogenophosphines and Related Compounds 69 pentachloride are the reactions leading to (85) 81 and (86).82983 The contrast between (80) and 2-methyl-1,3-dioxolone (87) is clearly related to the ease of fragmentation of (80) to give chloride ion. Since a previous study of the reaction leading to (85) has described the formation of 1,4-dichlorobutane (88) [cf. (84) 3, the reaction conditions would appear to be critical.84 The exchange reactions between fluorophosphoranes and silane derivatives have been utilized for the fluorination of alcohols, via their trimethylsilyl ethers (89).85,86 According to one of these reports, the ~~ pentaalkyl fluoride is generally accompanied by ~ l e f i n .Phosphorus fluoride similarly fluorinates siloxanes such as (90).87 ROSiMe3 (89)

+

PhPF4 --+

RF

+

PhP(O)F,

+

FSiMe,

Further examples of the preparation of phosphonates from acetals and and (92).90 phosphorus pentachloride include those leading to (91) The reaction of phosphorus pentachloride with t-butanol yields the phosphonate (93), which eliminates hydrogen chloride on treatment with base.Ol The phosphorus-carbon bond-forming steps of the reactions appear to involve the addition of phosphorus leading to (91)-(93) pentachloride to electron-rich olefins. 88s

81 82

83 84

86 86 87 88

89

90 91

S. V. Fridland, G. Kh. Kamai, L. V. Voloboeva, Zhur. obshchei Khim., 1970,40, 595. S . V. Fridland, S. K. Chirkunova, V. A. Kataeva, and G. Kh. Kamai, Zhur. obschchei Khim., 1971, 41, 554. S. V. Fridland, T. V. Zykova, S. K. Chirkunova, V. A. Kataeva, and G. Kh. Kamai, Zhur. obshchei Khim., 1971, 41, 1041. N. I. Shuikin, I. F. Bel'skii, and I. E. Grushko, Izoest. Akad. Nauk S.S.S.R., Otdel. Khim. Nauk, 1963, 557. D. U. Robert and J. G. Reiss, Tetrahedron Letters, 1972, 847. H. Koop and R. Schmutzler, J. Fluorine Chem., 1971, 1, 252. E. W. Kifer and C. H. Van-Dyke, Inorg. Chem., 1972,11,404. V. V. Moskva, G. F. Nazvanoya, T. V. Zykova, and A. I. Razumov, Zhur. obshchei Khim., 1971, 41, 1489. V. V. Moskva, G. F. Nazvanoya, T. V. Zykova, and A. I. Razumov, Zhur. obshchei Khim., 1971,41, 1493. V. V. Moskva, L. A. Bashirova, T. V. Zykova, and A. I. Razumov, Zhur. obshchei Khim., 1970, 40, 2764. V. V. Moskva, L. A. Bashirova, and A. I. Razumov, Zhur. obshchei Khim., 1971, 41, 2577.

70

Organophosphorus Chemistry CH,=CHCH(OEt),

+

so,

Pc15

0

II

+ CI,PC=CH(OEt)

I CH,CI (92)

PCI5

+

i benzene

Me3COH

0 CI 11 I Cl,PCH,CMe,

(93)

0

II

CI,P CH=C Me,

Salts are produced by the reaction of fluorophosphoranes with N-silylimines (94).O2. 93 Vinyl isocyanate reacts with phosphorus pentachloride to give a hexachlorophosphate salt (93, which yields the phosphonic dichloride (96) on hydrolysis and di~tillation.~~ Butyl cyanate reacts with phosphorus pentachloride to give two products, (97) and (98).s5 Me3SiN=PR3

+ Me,PF3

--+

(94)

C Hz = C Ho N= C = O

+

PCI,

[Me,PF,l- [Me,P(N=PK,),l+

-

[CI,PCH=CHNHCOCll+ P a 6 (95) i, SO, ii, A

+ O2

O3 O4

+

RCl

W. Stadelmann, 0. Stelzer, and R. Schmutzler, Chem. Comm., 1971, 1456. W. Stadelmann, 0. Stelzer and R. Schmutzler, 2. anorg. Chem., 1971, 385, 142. V. V. Doroshenko, E. A. Stukalo, and A. V. Kirsanov, Zhur. obshchei Khim., 1971,41, 1645.

s6

CldP-N=C=O

N. K. Kulibaba, V. I. Shevchenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1971, 41, 2105.

71

Halogenophosphines and Related Compounds

3 Phosphines containing a P-X Bond (X = Si, Ge, or Sn) Mislow’s group has continued to study inversion barriers in phosphines and arsines, and test the generality of the theoryQ6that barrier height is controlled by the electronegativity of the ligands. For example, the barrier in (99) is 18 kcal mol-1 less than that in (loo), and the difference was explained on this basis.Q7 The trimethoxysilylphosphine (101a) has a barrier 2 kcal mol-1 less than that of the trimethylsilylphosphine (101b),Q8 SiMe3

L4CPh Me (100)

(99)

Ph-P,

A

+)-

Ph-P,

SR3 (a)R = OMe (b)R = Me

6Me

‘Si(0Me)a

(101)

contrary to the predictions of the above theory,Qs and negative hyperconjugation [implying a contribution from (102) to the ground state of (101a) ] has been suggested as an e x p l a n a t i ~ n . ~ ~ The synthesis and uses of alkali-metal tetraphosphinoaluminates (103) continue to be of interest,O@and further examples of the synthesis of silylphosphines have appeared.loo Phenyl(trimethy1silyl)phosphine (104) has MAI(PHR1)4 (103) M = N a or Li R1 = H or Me

XSiR2,R3, -

PhPHK

+

R1HP.SiR2, R33--n

R1 = R3 = H, R2 = M e f o r n R1 = R2 = Me, R3 = H for n

MesSiCI

= =

0, I , or 2 0-3

PhPHSiMe3 (104) -

been prepared.lol A new synthesis of silylphosphine involves heating a mixture of phosphine and silane at 300 OC.lo2 The silicon-phosphorus bond of dimethyl(trimethylsily1)phosphine (105) is readily cleaved by a variety of covalent halides, as shown in Scheme 16.1°3 Further examples of insertion by carbon multiple bonds R. D. Baechler and K. Mislow, J. Amer. Chem. Soc., 1971, 93, 773. R. D. Baechler, J. P. Casey, R.J. Cook, G. H. Senkler, and K. Mislow, J. Amer. Chem. SOC.,1972, 94, 2859. Bs R. D. Baechler and K. Mislow, J. C. S . Chem. Comm., 1972, 185. J. A. Miller, in ‘Organophosphorus Chemistry’ ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1971, vol. 2, p. 52; 1972, vol. 3, p. 53. l o o G. Fritz and H. Schafer, Z. anorg. Chem., 1971, 385, 243. l o l M. Baudler and A. Zarkadas, Chem. Ber., 1971, 104, 3519. lo2 I. H. Sabherwal, and A. B. Burg, Inorg. Nuclear Chem. Letters, 1972, 8, 27. loS J. E. Byrne and C. R. RUSS,J. Organometallic Chem., 1972, 38, 319. g6

72

ISlCl,

Mc,PSiMe (105)

CEiI

! ,

SO,CI,

Organophosphorus Chemistry

Me3SiCI

Me3SiI MesSiCl

+ +

Me,PSiCI,

Me,PCF3

+ Me,PS02CI J.

Me,P(O)CI

+ SO,

Scheme 16

into germylphosphines have appeared, and confirm the trends previously established.lo4elo5 These are illustrated in Scheme 17 for the trialklygermylOMe (MeCO), R = Me

II I

> MeCCOGeMe3

I

PEt, R,GePEt,

CH,=CHCN

R=Et

Et,PCH,CH(CN) GeEt,

( I 06) MeCO,CH= CH, > R = Me

Me3GeOCH=CH2

Scheme 17

+

Me COP Et,

diethylphosphines (106). The n.m.r. spectra of a number of phenylphosphines of general formula (107) have been studied, and 31P shifts,lo6JPHvalues,1o7 and Jpsn values lo*measured, R,MPHPh M = Si, Ge, or Sn R = Me or Ph ( 107)

J. Satgd, C. Couret, and J. Escudie, J. Organometallic Chem., 1971, 30, C70. J. Satgd, C. Couret, and J. Escudie, J. Organometallic Chem., 1972, 34, 83. l o 6 G. Engelhardt, 2. anorg. Chem., 1972, 387, 52. lo' D. G. Harrison, S. E. Ulrich, and J. J. Zuckermann, Inorg. Chem., 1972, 11, 25. l o 8 W. B. Fox, D. E. Young, R. Foester, and K. Cohn, Inorg. Nuclear Chem. Letters,

lo4

lo5

1971, 7, 865.

4

Phosphine Oxides and Sulphides BY J. A. MILLER

Phosphine oxides are clearly not in vogue this year! For the first time since the inception of these Reports the number of new literature citations has gone down. The chapter has been divided into sections on the physical properties, the preparation, and the chemical properties of phosphine oxides. 1 Physical Aspects X-Ray determinations of structure have included the oxides (1) and (2),l the latter of which is shown2 to have a planar heterocyclic ring. The pK, values of a series of phosphine oxides (3) have been measured in d i g l ~ m e . The ~ mass spectra of 10-phenylphenoxaphosphineoxides (4a) and sulphides (4b),4 of ap-unsaturated phosphine oxide^,^ and of 0

CI

0 II Ph- P-CH,R1

I

R2

(a) R' (b) R' (c)

a

*

= =

R1 =

R2 = Ph; pK, 22.5 H, R2 = Ph; pK, 31.3 H, R2 = Me; pK, 31.7

(a) X = 0 (b)X = S

(3)

(4)

T. S. Cameron, J. C. S. Perkin ZZ, 1972, 591. L. Hungerford and L. M. Trefonas, J. Herocyclic Chem., 1972, 9, 347. E. S. Petrov, E. N. Tsvetkov, M. I. Kabachnik, and A. I. Shatenshtein, Zhur. obshchei Khim., 1971, 41, 1172. I. Granoth, J. B. Levy, and C. Symmes, J . C. S. Perkin ZZ, 1972, 697. G. M. Bogolyubov, V. F. Plotnikov, V. M. Ignat'ev, and B. I. Ionin, Zhur. obshchei Khim., 1971, 41, 517.

73

14

0rgan ophosphor us Chemistry R R 4\ X R (a) X (b)X

= =

0 S

R

=

H or Ph

(5)

3-phospholen 1-oxides (5a) and sulphides (5b) have been reported. E.s.r. spectra have been studied ’ for radical-anions generated by alkalimetal treatment of the oxides (6). The applications of n.m.r. to stereochemical problems in phosphine oxides have included the structure of phosphetan 1-oxides,*and the barriers to rotation in the oxide (7a) and the sulphide (7b).9 Extensive use of n.m.r. X II Ph-P-N(Pri), I CI (a)

X

(b) X

= 0 =

S

(7)

shift reagents has been made in the past year, particularly in the solution of structural problems in phosphine oxides.1°-14 More detailed discussion of some of this work appears in Chapter 11. 2 Preparation From Secondary Phosphine Oxides and Su1phides.-A novel reaction of phosphinates with sodium bis-(2-methoxyethoxy)aluminium hydride has been used to synthesize phosphine 0 ~ i d e s . l The ~ complex hydride is believed to generate a secondary phosphine oxide anion from the phosphinate, and this ion may be trapped by an alkyl halide to give a phosphine oxide. The reaction is general for tetrahedral esters, and is G. M. Bogolyubov, L. I. Zubtsova, N. N. Grishin, N. A. Razumova, and A. A. Petrov,

Zhur. obshchei Khim., 1971, 41, 517.

’ C. Thomson and D. Kilcast, Chem. Comm., 1971,782.

G . A. Gray and S. E. Cremer, Tetrahedron Letters, 1971, 3061. W. B. Jennings, Chem. Comm., 1971, 867. lo J. R. Corfield and S. Trippett, Chem. Comm., 1971, 721. l1 K.C.Yee and W. G. Bentrude, Tetrahedron Letters, 1971, 2775. l2 B. D.Cuddy, K. Treon, and B. J. Walker, Tetrahedron Letters, 1971, 4433. l3 G. P. Schiemenz and M. Rast, Tetrahedron Letters, 1971, 5685. l4 Y. Kashman and 0. Awerbouch, Tetrahedron, 1971, 27, 5593. l6 R. B. Wetzel and G. L. Kenyon, J. Amer. Chem. SOC.,1972, 94, 1774.

Phosphines Oxides and Sulphides

75

illustrated (Scheme 1) for the preparation of benzylmethylphenylphosphine oxide (8). The problem of the formation of diphosphine disulphides from phosphonothioic dichlorides and Grignard reagents has received further 0

II I

+

ph-P-OMe

H-

+ Ph-P-0 I Me

+

MeOH

I

Me

PhCH,CI

0 II Ph - P- CH,Ph

I

Me (8)

Scheme 1

study.la Although the dichloride (9a) gave only tertiary phosphine oxides (10a) with alkylmagnesium bromides, the corresponding phosphonothioic dichloride (9b) gave (lob) together with the disulphides (ll), all in low yield (Scheme 2). The Russian group rationalize the formation of (11) in X II

PhCH=CHPRZ

X II

R I

(a) X = 0

(b)X

=

S

PhCH=CHP- S

(9)

(12)

S

I PhCH=CHPCI II

l

k

Scheme 2 l6

B. V. Timokhin, E. F. Grechkin, A. V. Kalabina, V. V. Dorokhova, G. V. Ratovskii, and N. A. Sukhorukova, Zhur. obshchei Khim., 1971, 41, 2658.

76

Organophosphorus Chemistry

terms of an anionic intermediate (12), largely on the basis of analogy with the known behaviour of Grignard reagents towards phosphorus pentach1oride.l' A similar explanation of diphosphine disulphide formation has been presented previously.18 ,3-Cyanoethylphosphine oxides (1 3a) and sulphides (13b) are produced by the base-catalysed addition of secondary phosphine oxides or sulphides X II R,PCH, CH,CN (a) X (b) X

=

=

0, R S, R

= =

Ph o r alkyl Ph or alkyl

(13)

to acry10nitrile.l~ Further full details have appeared of the addition reactions of diphenylphosphine oxide and dimethyl phosphonate to cyclopentadienones.20 Despite the large volume of work 21 in this field, it is still not easy to distinguish the factors which control the additions of tervalent phosphorus compounds to molecules like tetraphenylcyclopentadienone (tetracyclone). For example, diphenylphosphine oxide reacts only at the a-carbon, giving adducts (14a-~),~O and methyl

/ Ph

I

Ph V 0P

I

Ph

h

0 (b) R'

(144

'

(cj R'

0 I1

+Me)ki

= =

H,R'

0

Ph, R2

= Ph = H

(14)

P I 1 f l Ph (a) K' (b) R'

= =

0 H, K' = Ph Ph, R2 = H

(15)

Scheme 3 l7 l8

lS

2o

B. V. Timokhin, E. F. Grechin, N. A. Tran'kova, and 0. A. Yakutina, Zhur. obshchei Khim., 1971, 41, 103. N. K. Pate1 and H. J. Harwood, J. Org. Chem., 1967, 32, 2999. A. N. Pudovik and T. M. Sudakova, Zhur. obshchei Khim., 1971, 41, 1962. J. A. Miller, G. M. Stevenson, and B. C. Williams, J . Chem. SOC.(C), 1971, 2714.

Phosphines Oxides and Sulphides

77

phenylphosphinite reacts only at the ,%carbon, giving adducts (1 5a, b) (Scheme 3),21a but analogous reactions of dimethyl phosphonate 21b can involve attack at either atom of the carbonyl group, as well as at the ring positions. In reactions with trialkyl phosphites,21b-dor with tertiary phosphines,z1c3 cyclopentadienones generally react at the carbonyl oxygen, although one clear exception to this rule has been observed.21~ 2oy

f

By Arbusov and Related Reactions.-Details have been presented 22 of the formation of phosphine oxides from alkyl benzoates and diphenylphosphinous chloride (16), although this route is not likely to be of preparative significance [see Chapter 3, Section 1, p. 521. The sulphides (17) have been prepared from alkyl chloroacetate~.~~ Further syntheses of benzoylphosphine oxides (18) have appeared, and their dipole moments Ph,PCI

+ ArC0,R

(16)

R'zPOR2

+

-

PhCOCI

h

0

II Ph,PR

-

00

II II

R'2PCPh R 1 = Et or Ph (18)

Clearly these oxides are extremely sensitive to experimental ~onditions.~~ By Oxidation of Phosphines.-The kinetics of the AIBN-catalysed autoxidation of various tervalent phosphorus compounds have been slb 21c 21d 21e

slf

22

23

I4 26

M. J. Gallacher and I. D. Jenkins, J. Chem. SOC.(C), 1971, 210. M. J. Gallacher and I. D. Jenkins, J. Chem. SOC.(0,1969, 2605. I. J. Borowitz, M. Anschel, and P. D. Readio, J. Org. Chem., 1971, 36, 553. A. J. Floyd, K. C. Symes, G. I. Fray, G. E. Gymer, and A. W. Oppenheimer, Tetrahedron Letters, 1970, 1735. R. C. Cookson and M. J. Nye, J . Chem. SOC.,1965, 2009. D. M. Roundhill and G. Wilkinson, J. Org. Chem., 1970, 35, 3561. A. I. Razumov, I. A. Krivosheea, and L. S. Alfonskaya, Trudy Kuzunsk Khim.-Technol. Znst., 1969, 40, 207 (Chem. Abs., 1971, 75, 140939.) S. T. McNeilly and J. A. Miller, J . Chem. SOC.(C), 1971, 3007. A. I. Razumov, E. A. Krasil'nikova, N. A. Moskva, T. V. Zykova, and L. A. Chemodanova, Zhur. obshchei Khim., 1971, 41, 2402. E. A. Ishmaeva, M. G. Zimin, R. M. Galeeva, and A. N. Pudovik, Zzuest. Akud. Nuuk S.S.S.R., Ser. khim., 1971, 538. J. A. Miller, in 'Organophosphorus Chemistry', ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1971, vol. 2, p. 56.

78

Organophosphorus Chemistry

y"\./f CN CN

~

R.

O,--PPh,

~

Ph3kOOR (19)

Ph3P=O

studied, and the relatively slow autoxidation of triphenylphosphine was ascribed to the stability of the radical chain carrier (19).2s Trifluoroacetyldiphenylphosphine is known 25 to oxidize to the phosphine oxide (20), and a rather unusual explanation of this reaction has been suggested by the same workers (Scheme 4). 27 The formation of 2,2,2-trifluoroethanol by 0 II F,CCPPh,

0 2

__j

0I + F3CC-PPh, I I 0-0

H,O

--+

Ph,$=O

+ CF3H + OH + C O , CFzCPPhZ

CF,CH,OH

-OH

t---

0 CF, 0 II I II PhzP-CH--O-PPh,

+

PhzP 0 II II t-- F3CCOPPhZ H,O

(20) Scheme 4

alkaline hydrolysis of (20) is not commented upon, although it might result from a disproportionation of trifluoroacetaldehyde, produced by cleavage of (20) by hydroxide ion. A number of phosphine oxides and sulphides have been prepared by the oxidation of the corresponding phosphine using standard reagents, e.g. (21),28,(22),29(23),30and (4a) and (4b).4

26 27 28

Y.Ogata, and M. Yamashita, J. C. S . Perkin ZZ, 1972, 730.

E, Lindner and H.-D. Ebert, Angew. Chem. Internat. Edn., 1971, 10, 565. L. Maier, Helu. Chim. Acta, 1971, 54, 1651. L. Maier, Helv. Chim. Acta., 1971, 54, 1434. H. Oehme, K. Issleib, and E. Leissring, Tetrahedron, 1972, 28, 2587.

79 By Miscellaneous Routes.-The synthesis of cyclic phosphine oxides from a,w-dibromides and tetraphenyldiphosphine has been described (Scheme 5 ) . The intermediate phosphonium salts are converted into the

Phosphines Oxides and Sulphides

Me

6

Ph,PPPh,

Br

/ \

/ \

Ph

Ph

Ph

0

(24)

Scheme 5

corresponding oxides by alkaline hydrolysis, e.g. (24), the first phosphocane reported, and (25).31 Good yields of tris(a-hydroxyalky1)phosphine oxides are reported from the electrolytic reduction of phosphorus in the presence Me

of aldehyde polymers, e,g. (26) from f o ~ m a l i n . ~ The ~ synthesis and resolution [using ( + )-9-camphorsulphonic acid] of a phospholen 1-oxide (27) has been 3 Reactions At the P=O or P=S Group.-An extremely simple and efficient synthesis of thiirans by treating oxirans with the phosphine sulphides (28) has been The reaction is catalysed by molar quantities of 31

s2

33 a4

K. L. Marsi, D. M. Lynch, and G . D. Homer, J. Heterocyclic Chem., 1972, 9, 331. I. M. Osadchenko, and A. P. Tomilov, Zhur. obshchei Khim., 1970, 40,698. G . Ostrogovich and F. Kerek, Angew. Chem. Internat. Edn., 1971, 10, 498. T. H. Chan and J. R. Finkenbine, J. Amer. Chem. SOC.,1972, 94,2880.

80

Organophosphorus Chemistry R,P=S

-t

0

H’\

57( S

+

R,p=O

trifluoroacetic acid, and the oxiran geometry (and the chirality at phosphorus in appropriate examples) is retained. The phosphetan 1-oxide (29) has been prepared with an l80label, and this compound used in a study of both l80exchange and epimerization reactions at different pH values.35 The epimerization is always slower than the lSO exchange, especially in acidic conditions, and in the pH 2 region this is believed to be the result of rate-limiting pseudorotation, in which the phenyl group and one of the phosphetan ring carbons are placed axially, as in (30). The

v

V

(Ep i iiie r i za t i o11)

corresponding intermediate (3 1) for exchange only requires that one of the ring carbons be placed axially. These results do not solve one of the main problems of our current picture of the role of quinquecovalent intermediates in phosphine oxide reactions: that of the rapid exchange of the oxide (32), observed several years ago 36-a point made by the author.

(32)

Previous suggestions 37 that the peracid oxidation of secondary phosphine oxides involves (33) as an intermediate have been confirmed from studies se 37

D. G. Gorenstein, J. Amer. Chem. SOC.,1972, 94, 2808. K. L. Marsi, J. Amer. Chem. SOC.,1969, 91, 4724. J. A. Miller, in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1972, vol. 3, p. 63.

81

Phosphines Oxides and Sulphides 0 II Ph+) PhCOO 4Ph' \H

0

d

0

II I Ph PhCOOP: I Ph H

0 II Ph2POH

-Q

-+OH

o"'

\

+ PhH

04 ' 0

P11

(34)

of deuterium isotope effects.38Cleavage of the oxide (34) with alkali results in loss of the phenyl

Additions to Unsaturated Phosphine Oxides.-Two very similar papers have described the addition of amines to bis-(1 -alkynyl)phosphine oxides, 0

/A'

R'

= Ph

I1 ,C=CR1 Php\CH2COR'

0

I1 ,C=CR1 PhP, CH=CR1 I

\

R'NH,

0

(

NHRj2 %

0

PhP CH=C, /R' I'

Scheme 6 38

II

PhP(CH2COR1)2

R. Curci and F. Difuria, Tetrahedron, 1971, 27, 4601. J. L. Suggs and L. D. Freedman, J . Org. Chem., 1971, 36,2566.

82 Organophosphorus Chemistry and the subsequent conversion of the initial adducts to new heterocycle^.^^^ 41 In one case40 the monoenamine adduct (35) cyclized directly during hydrolysis, and in the other 41 the hydrolysis of the bisenamine (36) led to a bisp-ketoalky1)phosphine oxide (37), which cyclized on treatment with ammonium carbonate (Scheme 6). Pyrazoles (38) are formed in good yields by the dipolar addition of N-phenylsydnone to diphenyl(prop- 1-ynyl)phosphine oxide at high temperature^.^^ Similar additions of diazodiphenylmethane to a series of vinylphosphine oxides result in the formation of 1-pyrazolines (39), which 0 II MeCGCPPh,

0 II R2 PCH=CH2

+

Ph2CN,

H

+

+ 4c\

P h N\ - - I C=O N-0

< S O T

R1 h y ( N R2 Me, R2 = P(O)Ph, S5:(: Me, R1 = P(O)Ph, 15;,’,

5p R1 = R2 =

(38)

0 I1 R2P- CF-CH2 \ N. CPh, qN’

I>

(39)

0

50 C

0

on further heating either isomerize to 2-pyrazolines or eliminate nitrogen to give cyclopropanes (40).43 The analogous reactions of allylphosphine oxides proceed sluggishly at 120 “C and give low yields of the cyclopropane Miscellaneous Reactions.-Details have appeared of a series of rearrangements of the phosphine oxides (41a, b) in which the diphenylphosphinyl group migrates to a carbonium centre /3 to the p h o ~ p h o r u s . ~ ~ 40

I1

M. Maumy, Bull. SOC.chim. France, 1972, 1600. J. C. Williams, J. A. Kuczkowski, N. A. Portnoy, K. S. Yong, J. D. Wander, and A. M. Aguiar, Tetrahedron Letters, 1971, 4749. A. N. Pudovik, N. G. Khusainova, and T. I. Frolova, Zhur. obshchei Khirn., 1971, 41, 2420.

43

Q4

A. N. Pudovik, R. D. Gareev, A. V. Aganov, 0.E. Raevskaya, and L. A. Stabrovskaya, Zhur. obshchei Khim., 1971, 41, 1008. P. E. Cann, D. Howells, and S. Warren, J. C. S. Perkin ZI, 1972, 304.

83

Phosphines Oxides and Sulphides

These migrations involve a 1,2-shift of the diphenylphosphinyl group from a tertiary to a primary carbon, but in a further paper 45 migrations from a tertiary carbon to a tertiary carbonium centre, in the oxides (41c, d), have been described (Scheme 7). Evidence for the intermediacy of the ion

(a) X (b) X (c)X (d) X

=

= = =

NH,, R1 = R2 = H OTS, R' = R2 = H OMS, R1 = H,R2 = Me OH, R1 = R? = Me

(41)

(4 14

Ph2!&

Brz

>

(43)

Scheme 7

(44)

(42) in the reaction of (41d) with hydrogen bromide comes from the related reactions of the oxide (43), e.g. the deterium incorporation from deuteriotrifluoroacetic acid into the methyl groups of (43), and bromination of (43) to give (44). 0

0

II II Ph, PCH2CNHOCOPh

Ph2PCH,N= C = O

0 I1

(EtO)Y (44)

Ph, PCH,CONHOH

Scheme 8 45

(45)

P. F. Cann, D. Howells, and S. G. Warren, Chem. Comm.,1971, 1148.

84

Organophosphorus Chemistry

Bis(N-diphenylphosphinylmethy1)urea (45) has been prepared by two routes (Scheme S), both involving migration of a (diphenylphosphiny1)methyl group to electron-deficient nitrogen and formation of the isocyanate (46).46 Further examples have appeared of the photolytic decomposition of a-diazoalkyldiphenylphosphineoxides (47), to give pho~phinylcarbenes.~~ The subsequent reaction pathway is highly dependent upon R, but the major competing reactions involve solvent trapping of the carbene, either directly [to give (48)] or after rearrangement [to give (49) 1. The a-azidophosphine oxide (50) has been prepared and used in the synthesis of the oxide (51) by standard

(37)

\

(48)

McOIl

0

II PhPCH(Ph)R I OMe

(49)

CH,PPh,

II

0 (51)

A detailed studyihas:been-made of the base-catalysed deoxygenation of carbonyl compounds with diphenylphosphine oxide (52) at high temperat u r e ~ .The ~ ~known 5 0 formation of good yields of trans-stilbene (56a) from benzaldehyde (53a) has been shown 49 to involve the intermediate formation of cis- and trans-stilbene epoxides, and their subsequent deoxygenation by (52). Similar deoxygenation of benzoylferrocene (53b) results in the formation of the ketones (54) and ( 5 3 , as well as the hydrocarbons (56b) and (57).49 The rationalization given in Scheme 9 has been presented to explain these ob~ervations.~~ 46

0. A. Mukhacheva, V. G . Nikolaeva, and A. I. Razumov, Zhur. obshchei Khim., 1971, 41, 1873.

49

M. Regitz, A. Liedhegener, W. Anschutz, and H. Eckes, Chem. Ber., 1971, 104,2177. D. Seyferth and P. Hilbert, Org. Prep. and Proced. Znternat., 1971, 3, 51. W. M. Horspool, S. T. McNeilly, J. A. Miller, and I. M. Young, J . C. S . Perkin I , 1972,

so

L. Horner, P. Beck, and V. G . Toscano, Chem. Ber., 1961, 94, 1323.

47 48

1113.

Phosphines Oxides and Sdphides

(a) R' (b)

R'

= =

Ph, R2 Ph, R2

= =

85

i

H FC

R'COR'

(53) 0 II R22RCCR1 R' = Ph R2 = FC

0

+

(55)

0 II PhzPO

11 R12R2CR2 R' = Ph R2 = FC

I,2-shift

f---

(54)

+

R1R2C=CR1R2 +-----

(a) R1 = Ph, R2 = H (b) R1 = Ph, R2 = FC

(56)

R'R2CHCHR1R2 R' = Ph, R 2 = FC (57)

Scheme 9

Ozonolysis of unsaturated phosphine oxides (58a) leads to the expected products (58b).51 Catalytic hydrogenation of arylphosphine oxides (59a) gives moderate yields of the corresponding cyclohexyl compounds (59b).52 Dimethylphosphine oxide (60) undergoes a complex sequence of exchange reactions with dimethylphosphinous Two of the suggested initial steps involve attack by the oxygen of (60) on halogenophosphines, as shown in Scheme 10 (see Chapter 3 for further details). The first-order J. L. Eichelberger and J. K. Stille, J. Org. Chem., 1971, 36, 1840. L. P. Zhuraleva and M. G. Suleimanova, Zhur. obshchei Khim., 1971, 41, 1944. F. See1 and K.-D. Velleman, Chem. Ber., 1971, 104, 2972.

I1 62

63

4

86

Organophosphorus Chemistry 0

0 II Ph PR2

I1 R'P[(CHZ)n R212 (a)

(a) R = -CH,CH=CH2

(b)R

=

R2

(b) R2

-CH2C02H

= =

Ph, n

=

C6Hll, n

0 or 1 = 0 or 1

(59)

(58)

thermal rearrangement of bis(diphenylphosphiny1) peroxide (61) has been shown to proceed with retention of phosphoryl l80labels,54an observation which is compatible with either a concerted process via the intermediate (62) or an intimate ion-pair reaction. In contrast, the analogous photolytic reaction results in scrambling of the lSO labels.54b Me2P(0)H

+

Me,PCI

--+

Me,P(O)CI

Me2P(0)OH Scheme 10 O* O* Ph2P II /0,0/PPh2II

64

A

o*

+ Me2PH

+

Me,PCl

o*

II II PhZP-0-P-OPh I Ph

(a) R. L. Dannley, R. L. Waller, R. V. Hoffman, and R. F. Hudson, Chem. Comm., 1971,

1362; (6)R. L. Dannley, R. L. Waller, R. V. Hoffman, and R. F. Hudson, J. Org. Chem., 1972, 37, 418.

5

Tervalent Phosphorus Acids BY B. J. WALKER

1 Introduction A great deal of the work published in the past year in this area of phosphorus chemistry has involved minor variations on old themes, and in this chapter only work which has some novelty is discussed in any detail. The use of phosphorous acid derivatives in synthesis has been reviewed.l 2 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-Attack on Saturated Carbon. The Arbusov reaction has been used extensively as a preparative method.2 Halogen has been the group most commonly displaced by phosphorus, although amino,4 alkoxy,6and acetate leaving groups have also been used. Under more forcing conditions, sulphur analogues [e.g. EtSPEtJ of tervalent phosphorus acids also undergo the Arbusov reaction with alkyl halides. The low reactivity of aromatic halides in the Arbusov reaction has been partially overcome through the use of palladium catalysts.s The reaction of phosphites with diphenyliodonium iodide in the presence of copper salts gives arylphosphonates (l), presumably by initial nucleophilic substitution and an Arbusov r e a ~ t i o n . ~ Anionic resins also appear to catalyse the 2

6

*

J. Barycki, Wiad. Chem., 1971, 25, 123 (Chem. Abs., 1971, 75, 4859). E.g. P. Burns, G . Capozzi, and P. Haake, Tetrahedron Letters, 1972, 925; 0. F. Voziyanova, S. N. Baranov, and S. V. Krivun, Zhur. obshchei Khim., 1970, 40, 1905 (Chem. Abs., 1971, 75, 6028). E.g. M. B. Gazizov, D. B. Sultanova, A. I. Razumov, L. P. Ostanina, and A. M. Pusalkina, Zhur. obshchei Khim., 1971, 41, 2575 (Chem. A h . , 1972, 76, 113 302). E.g. B. E. Ivanov and S. S. Krokhina, Izvest. Akad. Nauk S.S.S.R., Ser khim., 1971,2493 (Chem. Abs., 1972, 76, 127 085). E.g. B. E . Ivanov and S. S. Krokhina, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1970,2629 (Chem. Abs., 1971, 75, 6034.) E.g. M. B. Gazizov, D. B. Sultanova, V. V. Moskva, A. I. Maikova, and A. I. Razumov, Zhur. obshchei Khirn., 1971, 41,932 (Chem. Abs. 1971, 75, 49 216); B. E. Ivanov, L. A. Valitova, and S. S. Krokhina, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 1502 (Chem. Abs., 1971, 75, 986 276). E.g. A. I. Razumov, E. A. Krasilnikova, N. A. Moskva, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1971, 41, 1498 (Chem. Abs., 1971, 75, 129 890); E. A. Krasil'nikova, N. A. Moskva, and A. I. Razumov, Zhur. obshchei Khim., 1970,40, 2765 (Chem. Abs., 1971, 7 5 , 2 0 516). Ger. Offen. 2 118 223 (Chem. Abs., 1972,76, 34 399). A. G. Varvoglis, Tetrahedron Letters, 1972, 31.

87

88

Organophosphorus Chemistry 0

MeOCHMe Me<)OMe

+ ’

Arbusov reaction, causing rearrangement lo of the cyclic phosphite (2) to the phosphonate (3) even at - 5 “C. A mixture of acetylenic (4) and allenic ( 5 ) products has been obtained from the reaction of propargyl bromide with triethyl phosphite.ll The first example of a crystalline Michaelis-Arbusov intermediate ( 6 ) obtained from a trialkyl phosphite has been isolated from the reaction of (EtO),P

+

=

H C E C CH,Br

0

II

( E t 0 ) 2 P . C H = C =CH2

(RO)3P R

-

+

+ Me1

neopentyl

--+

+ +

0

(RO),PMe I(6)

II

0

I1

(EtO),P-CMe=CH.P(OEt),

-

0 I1 (RO),PMe

+

RI

(7)

trineopentyl phosphite with methyl iodide.12 The intermediate is unstable in solution, decomposing to give the normal Arbusov product (7), and its n.m.r. spectrum suggests an ionic rather than a quinquecovalent structure. The stability of (6) is presumably due to the resistance of the neopentyl group to &2 reaction, although the 5”2 nature of its ultimate decomposition is evidenced by the lack of rearrangement in the alkyl halide produced. Russian workers have isolated l3 a variety of compounds analogous to ( 6 ) lo l1 l2 l3

A. V. Bogatskii, T. D. Butova, and A. A. Kolesnik, Zhur. obshchei Khim., 1971, 41, 1875 (Chem. Abs., 1972, 76, 3203). G. Peiffer, J. P. Bianchini, J. Llinas, and J. C . Traynard, Ann. Fac. Sci.Marseille, 1970, 43A, 109 (Chem. Abs., 1971, 75, 20508). H. R. Hudson, R. G . Rees, and J. E. Weeks, Chem. Comm., 1971, 1297. L. V. Nesterov and N. A. Alekandrova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 415 (Chem. Abs., 1971,75, 20 509).

89

Tervalent Phosphorus Acids

from the reaction of phosphonites with alkyl halides, although again this was only possible for compounds containing branched-chain alkoxy-groups. Edmundson and Mitchell have investigated l4 the Arbusov reaction of the bicyclic phosphite (8) with a number of halides. The phosphonates obtained are attributed the structure (9) on n.m.r. evidence and in view of the known preference for the Arbusov reaction of five- over six-membered rings in monocyclic examples.

R32P-N=C,

,OR'

R2

Me

3- Me1 + R 3 2 P - N = C <

+

OR* R2

Methyleneaminophosphines (lo), on treatment with methyl iodide, give the expected phosphonium salts (1l), which on thermolysis undergo a reaction analogous to the Arbusov reaction to give imidopho~phoranes.~~ Various phosphonates l6 and phosphine oxides l7 have been prepared by the reaction of the anions (RO),PzO- Na+ and R,P-O- Na+ with alkyl halides. The analogous reactions of the chlorohydrin (12) with sodium diethyl phosphonate give the cyclic phosphonate (13) as a mixture of geometrical isomers of approximately equal stability.l* Attack on Unsaturated Carbon. The addition of tervalent phosphorus nucleophiles to a wide range of activated olefins, including barbituric l4 15

l6 l7

R. S. Edmundson and E. W. Mitchell, J. Chem. SOC.( C ) , 1971, 3179. A, Schmidpeter and W. Zeiss, Chem. Ber., 1971, 104, 1199. P. J. Majeswki, R. Bodalski, and J. Michalski, Synthesis, 1971, 140 (Chem. Abs., 1971, 74, 125 349); L. Maier, Phosphorus, 1971, 1, 67. R. A. Malevannaya, E. N. Tsvetkov, and M. I. Kabachnik, Zhur. obshchei Khim., 1971, 41,2359 (Chem. Abs., 1972, 76, 113 317). K. Bergesen and T. Vikane, Acta Chem. Scand., 1971, 25, 1147 (Chem. Abs., 1971,75, 88 707).

90

Organoph ospho r us Chemistry (Et 0 ) P

-

0, + Me C H C1(CH, ) 0H (12)

OEt

OEt

I

I

acids,la fulvenes,20A2-isoxazolin-5-ones,21and acrylic acid derivatives,22 has been investigated. The ratio of the products (14) and (15) from the addition-elimination reaction of trimethyl phosphite with perchlorobutadiene has been determined 23 as 69 : 31. CI,C= CCI-CCl=CCl,

+

(MeO),P

i 0

II Cl,C=CCI - C P(OMe), II CCI,

-

+

0 II Cl,C= CCI*CCI=CCI- P (OMe),

(15)

(14)

Dibutyl acetyl phosphite and acrolein react to give the phosphonate (1 6) in low yield.24 A cyclic mechanism is suggested, but an intermolecular reaction would seem equally possible. The analogous product (17) is obtained 25 from a similar reaction of the germyl phosphite (18). The reaction of phosphites with trifluoromethyl-substituted 2-aza-l,3butadienes (19) gives the adducts (21), the structure and stereochemistry B. A. Arbusov, T. D Sorokina, and V. S. Vingradova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 573 (Chem. Abs., 1971, 75, 63905). 2 0 G I. Kolesnikov, V. A. Burtsev, and N. K. Strizhov, Zhur. obshchei Khim., 1971, 41, 305 (Chem. A h . , 1971, 75, 49 235). z1 T. Nishiwaki and K. Kondo, J. C. S. Perkin I, 1972, 90. 22 T. Kh. Gazizov, Yu. M. Mareev, V. S. Vinogradova, A. N. Pudovik, and B. A. Arbusov, Izvest. Akad. Nauk S.S.S.R.,Ser. khim., 1971, 1259 (Chem. A h . , 1971, 75, 88 721); A. N. Pudovik and T. M. Sudakova, Zhur. obshchei Khim., 1971,41,1962 (Chem. Abs., 1972, 76, 24 330). 23 K. Gorzny, 2 . Naturfursch., 1971, 26b, 1193 (Chem. Abs., 1972, 76, 59 709). 2 4 L. I. Mizrakh, V. I. Mamonov, V. I. Svergun, and L. N. Kozlova, Zhur. obshchei Kfzim., 1971, 41, 1406 (Chem. A h . , 1971, 75, 129 882). 25 Z. S. Novikova, S. N. Mashoshina, and I. F. Lutsenko, Zhur. obshchei Khim., 1971, 41, 2110 (Chem. A h . , 1972, 76, 25 386). l9

Terualent Phosphorus Acids

91

(BuO),POCOMe

+ CH,=CH*CHO

(BuO),PCH,CH=CH -0COMe (16)

(RO),POGeEt,

+

(’*)

I

CH,=CH.CHO

$ 0 II (ROI2P*CH,-CH=CH - OGeEt, (17)

of which were determined from their n.m.r. spectra.2s A mechanism involving an intermediate ylide (20) is suggested. A similar reaction with N-(2,2,2-trichloroethylidene)benzamide gives the phosphonate (22). CF,

+

MeCl

Schmidpeter has reported 27 a novel 1,3-~ycloaddition reaction of methyleneaminophosphinesto activated double and triple bonds. Acrylic acid derivatives give the azaphospholens (23), while acetylenes give azaphospholes (24). 26

27

K. Burger, J. Fehn, J. Albanbauer, and J. Friedl, Angew. Chem. Internat. Edn., 1972, 11, 319. A. Schmidpeter and W. Zeiss, Angew. Chem. Znternat. Edn., 1971, 10, 396.

92

Organophosphorus Chemistry R', P - N =CR2,

MeO,C'

C0,Me

Mixtures of cis- and trans-enaminephosphonates were obtained 28 from the reaction of secondary phosphites with ynamines, the stereochemistry being inferred from n.m.r. data in each case. The additions of dialkyl phosphites and secondary phosphine sulphides to Schiff bases have been used to prepare a-aminophosphonates 29 and tertiary phosphine s ~ l p h i d e s respectively. ,~~ Trialkyl phosphites react 31 readily with (N-phenylbenzimidoy1)formicacid (25) to give the phosphonate (26) and the formate (27). Alternative mechanisms, both involving initial

PhC=NPh

I

CO,R

+

0

II

(RO),PCHPh*NHPh

+

CO,

(26)

(27)

(C5HI0N),P

+ R - d = N - NPh (28)

\ (CgHlo'N)a P = C R - N = N P h (29)

28 28

30

31

N. Schindler and W. Ploeger, Chem. Ber., 1971, 104, 2021. B. P. Lugovkin, Zhur. obshchei Khim., 1970, 40, 2391 (Chem. Abs., 1971, 75, 20 507); V. JagodiC and Lj. Tusek, J . Org. Chem., 1972, 37, 1222. L. Maier, Phosphorus, 1971, 1, 71. M. M. Sidky, F. M. Soliman, and R. Shabana, Tetrahedron, 1971, 27, 3431.

93

Tervalen t Phosphor us Acids

nucleophilic attack of the phosphite on the imide, are proposed. Attempts at a similar reaction with dialkyl phosphites were unsuccessful. Russian workers have obtained32 the ylides (29) from the reaction of phosphorotripiperidide with nitrilimines (28) in the presence of triethylamine. Nitriles have been obtained from both 1,2,5-0xadiazoles and their oxides on treatment with triphenyl phosphite; the oxides are probably first reduced to the oxadiazoles by the reagent.33 A possible mechanism would involve addition of phosphite to give the betaine (30), followed by ring-opening and elimination of phosphate.

I

-(l’llo)3 PO

2RC-N

RwcoNH2 Rwco2Me N

N

The reactions of triethyl phosphite with 5-amino- (31) and 5-alkoxy- (32) isoxazoles have been extensively i n ~ e s t i g a t e d .In ~ ~ both cases aziridinyl phosphonates were obtained, the best yields being in the presence of a proton donor. Similar reactions with the isomeric 2H-azirines (33) and (34) 3a

33 3p

S. P. Konotopova, V. N. Chistokletov, and A. A. Petrov, Zhut. obshchei Khim., 1971, 41, 235 (Chem. Abs., 1971, 75, 20533). S. M. Katzman and J. Moffat, J . Org. Chem., 1972, 37, 1842. T. Nishiwaki and T. Saito, J . Chem. Sac. (C), 1971, 3021.

94

Organophosphorus Chemistry

gave analogous products, and it is suggested that these azirines are intermediates in reactions of isoxazoles. Studies of the reactions of cyclopentadienone derivatives with tervalent phosphorus compounds have continued. The exothermic reaction 35 of phencyclone (35) with trimethyl phosphite in the absence of solvent gave (37), presumably via the intermediate (36). Evidence for the involvement

(MeO),P -

of (36) was obtained from reactions in protic solvents, which gave (38). The ketone (38) was also obtained from the reaction of phencyclone with dimethyl phosphonate. The reactions of tetracyclone with secondary phosphites 37 and secondary phosphine oxides 37 have been further investigated. The reactions are complex and the products are highly dependent on the conditions used. In view of this it is not surprising that some disagreement has arisen. Miller has attempted to correlate all his previous work and draw some overall conclusions.37 A variety of products have been obtained from the reaction of diphenylphosphine oxide (39) with tetracyclone, depending on the conditions used. However, in all cases phosphorus appears to attack the carbon 01 to the carbonyl group, and it is the site of protonation which determines the nature of the final product. The products from reactions with dimethyl phosphonate again depend on the conditions, (40),(41), and (42) being obtained in the absence of solvent at reflux, whereas 369

35 36 37

B. A. Arbusov, A. V. Fuzhenkova, A. F. Zinkovskii, and L. Ya. Savchenko, Doklady Akad. Nauk S.S.S.R., 1971, 199, 339 (Chem. Abs., 1971, 75, 140939). A. V. Fuzhenkova, A . F. Zinkovskii, and B. A. Arbusov, Doklady Akad. Nauk S.S.S.R., 1971, 201, 632 (Chem. Abs., 1972, 76, 127092). J. A. Miller, G . Stevenson, and B. C. Williams, J. Chem. SOC.( C ) , 1971, 2714.

pH-

Tervalent Phosphorus Acids

00 II II Ph,P-PPh,

+

Ph,PH //

95

Ph

I1

(39)

Ph

+

0

:Ph $p

“Ph

p

Ph H G L ---Ph - P h ,

+

Ph 0

0

the phosphonates (43) and (44) were isolated from reactions in ether at room temperature under base catalysis. Russian workers 36 have also obtained (44) from a similar reaction using triethylamine as a catalyst and

g,ph

Ph ?I (MeO),PH

+

Ph

Ph

Ph

Ph

---+ph(.-$I&OMe)z

0

0

Ph (43)

“Ph 0

+

(41)

+

$ Ph -)p

Ph

HO P(OMe), //

0 (44)

Vh ’

Ph

Ph

observed its rearrangement to the phosphate over several days. Miller suggests3‘ that the results are best explained by reactions of the tervalent forms of the secondary phosphite and phosphine oxide.

96 Organophosphorus Chemistry A number of reports of the 1,4-cycloaddition of phosphites to conjugated dienes 38 and a/?-unsaturated ketones 39 have appeared (see also Chapter 2). a-Allenyl ketones undergo the expected cycloaddition of phosphite or phosphinite to give 40 the phosphoranes (45), and for the chloroketone (46) cycloaddition is preferred to the alternative Perkow reaction. The adduct (47) undergoes exothermic acidic hydrolysis to give a mixture of vinylphosphonates.

(MeO)PK1, + R 2 C O * C H = C = C H 2 + R' = Ph or OK

I

M e 0 R' K 1 (45)

CICH.) (MeO),P

+

%? /r;

CICH,CO-CH=C=CH2 + 0,

(46)

1-1

M e 0 0 OMe

Me

(37)

38

sg

40

Zh. L. Evtikhov, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1971, 41, 479 (Chem. Abs., 1971,75,49 233); Zh. L. Evtikhov, B. B. Shurukhin, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1971, 41, 480 (Chem. Abs., 1971,75,49 230); N. A. Razumova, L. I. Zubtsova, and A. A. Petrov, Zhur. obshchei Khim., 1970, 40, 2563 (Chem. Abs., 1971, 75, 36260). B. E. Ivanov and L. A. Kudryavtseva, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 125 (Chem. Abs., 1971, 75, 36253); A. K. Voznesenskaya, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1971, 41, 234 (Chem. Abs., 1971, 75, 49 236); B. A. Arbusov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Doklady Akad. Nauk S.S.S.R., 1971, 200, 847 (Chem. Abs., 1972, 76, 25 367); B. A. Arbusov, E. N. Dianova, V. S. Vinogradova, and M. V. Petrova, Doklady Akad. Nauk S.S.S.R., 1970, 195, 1094 (Chem. Abs., 1971, 75, 6025); B. A. Arbusov, E. N. Dianova, and V. S. Vinogradova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 2543 (Chem. Abs., 1971, 75, 6014). G. Buono and G. Peiffer, Tetrahedron Letters, 1972, 149.

Teuvalent Phosphor us A c ids

97

Ogata and Yamashita have studied the kinetics of the reaction of phosphites with aliphatic a-diketones 42 and with benzils 4 3 ~44 to give the adducts (48). In all cases the reaction was second-order, first-order in phosphite and ketone. For symmetrical diketones steric effects appear to control the rate, while in unsymmetrical examples electronic effects are much more i m p ~ r t a n t .In ~ ~cyclic diketones the rate constant decreases 419

R-CO-CO-R+ (MeO),P

-

0-

I

+

R-C-P(OMe), I RCO (49)

with increase in ring size, with an especially large change from five- to six-membered rings.42 This suggests that the reaction takes place with a relief of strain through changing hybridization at carbonyl carbon (sp2 --f sp3). In view of this, a mechanism involving initial attack at carbonyl carbon (49) followed by rearrangement is suggested. For reactions with benzils, large positive p values are The effect of variations in the phosphite is discussed in terms of both polar and steric effects and the correlation between 31P n.m.r. chemical shift of the phosphite and The authors suggest that in all relative reaction rate is inve~tigated.~~ cases the reactions take place by initial attack of phosphite at carbonyl carbon. The cyclobutenedione (50) reacts with phosphite at a single carbonyl group rather than by c~cloaddition.~~ Trimethyl phosphite, which was previously reported not to react, gives the phosphonate (51), while dimethyl phosphonate gives products from addition at both carbonyl and alkene. 41 43

d4 46

Y. Ogata and M. Yamashita, Tetrahedron, 1971, 27, 3395. Y. Ogata and M. Yamashita, J . C. S. Perkin 11, 1972, 493. Y. Ogata and M. Yamashita, J. Org. Chem., 1971, 36, 2584. Y. Ogata and M. Yamashita, Tetrahedron, 1971, 27, 2725. P. R. 0. De Montellano and P. C. Thorstenson, Tetrahedron Letters, 1972, 787.

98

Organophosphorus Chemistry

Ph

//

0

4,5-Dihydro-1,3,5-Pv-oxazaphospholes (52) have been prepared 46 for the first time by the cycloaddition of phosphites to 1,1,1,3,3,3-hexafluoro-2(acy1imino)propanes.

The reactions of dialkyl phosphonates and secondary phosphine oxides with aldehydes have been used to prepare a-hydroxyalkylphosphonates 4' and various a-functionalized tertiary phosphine In contrast to previous reports, dialkyl phosphonates have been shown 49 to react exothermically with benzophenone in the presence of base to give 0 4

(RO), PH

+

Ar,CO

e

~

0 II Ar,CHOP(OR), ~ ~ ~

f

0 II (R0)2P-C(OH)Ar, (54) 46 47

48

4Q

K. Burger, J. Fehn, and E. Moll, Chem. Ber., 1971, 104, 1826. R. Shukla and R. S. Tewari, Indian J. Chem., 1971, 9, 658 (Chem. Abs., 1971, 75, 88 700). N. Kreutzkamp, K. Herberg, K. Laemmerhir, and E. Schmidt-Samoa, Arch. Pharm., 1971,304,896 (Chem. Abs., 1972, 76, 59708). H. Timmler and J. Kurz, Chem. Ber., 1971, 104, 3740.

Terualent Phosphorus Acids S

(RO)2&l

99 0

+ Ar,CO

Na

PhH

*

II

(RO) P SCH Ar (55)

phosphates (53). However, at room temperature and low base concentrations the a-hydroxyphosphonate (54) is isolated. A similar reaction with diethyl thiophosphonate gives the thiophosphate (55). The a-aminobenzylphosphoramide (56) has been obtained from the reaction of benzaldehyde with tris(dimethylamin~)phosphine,~~ while benzaldehyde and diethylphosphorous acid isocyanate give 51 a low yield of the cyclic imide (57), presumably by the mechanism shown. (Me,N),P

+ PhCHO

(EtO),PNCO

+

-

CH,CI,

PhCHO -

oc,

0

II

(Me,N),PCHPh.NMe2 (56)

,z-

+,m=c=o

(Et0)2P,

I

CHPh

N (Et 01,P4 C ' =0 \ / PhHC-0 (57)

0SiR2,

(59)

(58)

Secondary phosphites and thiophosphites react 5 2 with silylketens to give vinylphosphonates (58), presumably through rearrangement of (59). The reactions of keten dimers with tervalent phosphorus compounds are much more complicated and have been the subject of extensive study by Bentrude 60

51 52

E. E. Nifant'ev and I. V. Shilov, Zhur. obshchei Khim., 1971, 41, 2372 (Chem. Abs., 1972, 76, 113 314).

R. I. Tarasova, N. M. Kislitsyna, and A. N. Pudovik, Zhur. obshchei Khim., 1971,41, 1972 (Chem. Abs., 1972,76, 34 357). N. I. Savelpeva, A. S. Kostyuk, Yu. I. Baukov, and I. F. Lutsenko, Zhur. obshchei Khim., 1971, 41,485 (Chem. Abs., 1971,75,20495).

1 00

Orgnnophosphorits Chemistry

\

Me

Me Me

/

0”

0’+

Me

Me

Me

\ /

C

II ROCO-CMe2-C- OP(OR)2

I!

Terualent Phosphorus Acids

101

and his c o - ~ o r k e r s . ~The ~ - ~products ~ from the reaction of the two dimers of dimethylketen (60) and (61) appear to depend on the phosphite used:53 whereas (60) gives the vinylphosphate (62), the dione dimer (61) can give (62) or the phosphonite (63). The results are explained by initial attack at carbonyl carbon in all cases, followed by ring-expansion. The intermediacy of (64) allows interconversion of the initially formed betaines, depending on the stability of the ring-expanded products. The reactions of both acyclic 54 and cyclic 55 aminophosphites with (60) and (61) were also investigated. In the acyclic case, products similar to those observed in reactions with phosphites were obtained and an analogous reaction mechanism was In the case of cyclic aminophosphites, quinquevalent phosphorus intermediates [e.g. (65) ] were isolated in addition to the expected products.66

The same workers have investigated 56 the reactions of tervalent phosphorus compounds with dimethylketen itself at - 70 “C. N.m.r. spectra suggest that the quinquecovalent compounds (66) obtained follow the expected rules for the stereochemistry of substituents.

The reaction of phosphites with carboxylic acid chlorides5’ and with thionocarboxylic acid chlorides 58 to give the corresponding phosphonates (67) and (68) has been studied. Hudson and Brown have shown that ring strain in the phosphorus nucleophile can suppress the Arbusov reaction with acid ~ h l o r i d e s .Whereas ~~ the acyclic aminophosphite (69) gives (70), presumably via an intermediate salt (71), reaction with the cyclic compound 63

W. G. Bentrude, W, D. Johnson, W. A. Khan, and E. R. Witt, J . Org. Chem., 1972,37, 631.

67

W. G. Bentrude, W. D. Johnson, and W. A. Khan, J. Org. Chem., 1972,37, 642. W. G. Bentrude, W. D. Johnson, and W. A. Khan, J . Amer. Chem. SOC.,1972,94,923. W. G. Bentrude, W. G. Johnson, and W. A. Khan, J. Amer. Chem. SOC.,1972,94,3058. V. M. D’yakov, G . S. Gusakova, E. I. Pokrovskii, and T. L. D’yakova, Zhur. obshchei Khim., 1971,41,1035 (Chem. Abs., 1971,75,87 729); D. A. Nicholson and H. Vaughn, J . Org. Chem., 1971, 36, 3843. V. V. Yakshin and L. I. Sokal’skaya, Zhur. obshchei Khim., 1971,41,484 (Chem. Abs.,

69

C. Brown and R. F. Hudson, Tetrahedron Letters, 1971, 3191.

64

1971, 75,20 532).

102

Organophosphorus Chemistry (R20)2PNR1,

+

R3COX

--+

( ~ 2 0 ) , $ - ~ ~ 1 ,

I

0 II

ROPCOR3

I

[:;PNEt2

+ PhCOCl

-

X-

+ R2X

NR*~

(70)

c1-

[;;P-p COPh

(72)

(72) involves nucleophilic nitrogen, rather than phosphorus, to give the phosphorus halide (73). The yields of the products suggest that the Arbusov reaction must be at least lo3 times faster for the acyclic case. Similar large decreases in reactivity of cyclic phosphites with a variety of electrophilic reagents have been observed.GoThe ratio of the rate constants for cyclic and acyclic compounds is thought to depend on the degree of bond formation in the transition state since this will control the 0-P-0 bond angle and hence the strain energy. The largest effects are found when the substrate is a proton (the rate ratio is estimated as and this difference in basicity explains the relative stability of (74), compared with (73, towards hydrogen chloride. The kinetics of the Perkow reaction to give vinyl phosphates (76) have been studied by both titration G 1 and n.m.r.G2methods. Both approaches

[0O'PCI ' (74) 60

61 62

(EtO),PCI (75)

C . Brown, R. F. Hudson, V. T. Rice, and A. R. Thompson, Chem. Comm., 1971,1255. A. Arcoria and S. Fisichella, Tetrhedron Letters, 1971, 3347. I. J. Borowitz, S. Firstenberg, G . B. Borowitz, and D. Schuessler, J . Amer. Chem. SOC., 1972, 94, 1623.

Terualent Phosphorus Acids

103

show that the reaction is second-order overall, and the p values determined support the suggestion that there is initial rate-determining attack of phosphorus at carbonyl carbon followed by rearrangement. The preferential formation of the (E)-vinyl phosphate (76) is explained in terms of (R'O), P 4- Ar * C0.CHCIR2

-

(R10)3$-CAr -CHXR2 I 0-

phosphite attack on the less hindered side of the halogen-eclipsed form of the halogenoketone (although the energies involved differ by an order of magnitude).s2 Confirmation of the stereochemistry of the vinyl phosphates obtained in this way is available from their n m r . spectra and by comparison with compounds prepared from the reaction of enolate anions with dialkyl phosphoro~hloridates.~~ Attack on Nitrogen. Imidophosphoranes have been obtained from the reactions of both phosphorous esters 64 and amides 65 with azides. 2-Alkylbenzoxazoles are the products from the exothermic reaction of the aryl azide (77) with triethyl phosphite.66 The intermediacy of the imide (78) was supported by U.V. and n.m.r. spectra of the reaction mixture and confirmed by its isolation as a yellow oil from the reaction at 0 "C in hexane.

aocoR a +

OCOR

(EtO),P

--+

N=P(OEt),

N3

(77)

e3 e4

65

ae

(78)

I. J. Borowitz, S. Firstenberg, E. W. R. Casper, and R. K. Crouch, J. Org. Chem., 1971, 36, 3282. G. K. Genkina, V. A. Gilyarov, E. I. Matrosov, and M. J. Kabachnik, Zhur. obshchei Khim., 1970, 40, 1496 (Chem. A h . , 1971, 75, 49 212). V. A. Shokol, L. I. Molyavko, and G. I. Derkach, Zhur. obshchei Khim., 1971,41,2379 (Chem. Abs., 1972, 76, 112 593). L. J. Leyshon and D . G. Saunders, Chem. Comm., 1971, 1608.

104

Organophosphoriis Chemistry

Substituted benzamidoximes react 67 with tris(dimethy1amino)phosphine to give 3,4-benzo-1,2-azaphosphole2-oxides (79).

Attack on Oxygen. Dichlorophenylphosphine reacts with propene oxide and 2-methyloxetan to give products (80) and (81) which are logically derived from initial attack at oxygen.68 The cyclohexadienone (82) reacts with two moles of sodium diethyl phosphonate to give 69 4-methylphenyl diethyl phosphate and the triene (83). A mechanism involving dichlorocarbene is proposed with a first step which could involve attack at either carbonyl oxygen or carbon.

-

PhPCI,

9, + MeCH-CH,

PhPC1,

+

PhPCI.OCHMe-CH,Cl

PhPCI.OCHMe.CH,CH,Cl (8 1)

Under anhydrous conditions benzaldehyde and diphenylphosphine oxide anion give a mixture of stilbene and stilbene oxide,'O while a similar reaction with benzoylferrocene gives a mixture of products, including a small amount 67

6B 70

L. Lopez and Barrans, Compt. rend., 1971, 272, C,1591. 0. N. Nuretdinova, L. Z. Nikonova, and V. V. Pomazanov, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 2225 (Chem. Abs., 1972, 76,46253). B. Miller, Tetrahedron Letters, 1972, 1019. W. M. Horspool, S. T. McNeilly, J. A. Miller, and I. M. Young, J. C. S. Perkin I, 1972, 1113.

105

Tervalent Phosphorus Acids

of the olefin (84). Several mechanisms are considered, but that involving initial attack at carbonyl oxygen to give (85), followed by further reaction with carbonyl compound and deoxygenation, is preferred. PhCOFc

+ P h 2Y P-0

Fc = Ferrocenyl

'f0

R R

+

I

0 Ph,P@ '0-

-

Ph,

/Fc

/c=c\ Ph Fc (84)

R2

,c\?

0

II

R2C y 0 - P P h , \0-

P h ++ p-0

-

Ramirez has used 71 the reaction of highly electrophilic carbonyl compounds with a variety of tervalent phosphorus compounds in a general synthesis of 1 ,Zoxaphosphetans [e.g. (86) 1.

The kinetics of the oxidation of diarylphosphine oxides with perbenzoic acid have been investigated and the kinetic deuterium isotope effects 71

F. Ramirez, G. V. Loewengart, E. A. Tsolis, and K. Tasaka, J . Amer. Chem. Soc., 1972, 94, 3531.

106

Organophosphorus Chemistry 0

II Ph-CO-OOH Ar,PX X = HorD

+

(87)

Ar-CO.OX

I

+

0

II

ArPOX

determined.72 On the basis of these results a two-step mechanism is proposed, involving initial formation of a reactive peroxide intermediate (87) followed by decomposition to products. Allylic sulphenate esters, produced by 2,3-sigmatropic rearrangement of the equivalent sulphoxides, undergo rapid nucleophilic cleavage in the presence of pho~phites.'~Refluxing allyl p-tolyl sulphoxide in THF with four moles of phosphite gives dimethyl allylphosphonate (88), methyl p-tolyl sulphide, trimethyl phosphate, and allyl p-tolyl sulphide (89). A mechanism is proposed that involves nucleophilic substitution at oxygen to give the salt (90) followed by the two possible Arbusov routes. No products derived from initial attack at sulphur to give (91) were observed,

I

( MeO) 3POCH2*CH=CH, +

0

II

( Me0)2PCH,CH=CH,

(88)

+

M e So M e

4 -SR

(90)

I I

(MeO),P=O

+

H,C=CH* CH,. S (89) 72

73

R. Curci and F. Di Fucia, Tetrahedron, 1971, 27, 4601. D. A. Evans and G. C. Andrews, J. Amer. Chem. SOC.,1972, 94, 3672.

Tervalent Phosphorus Acids

107

+

( Me0)3P-S-CH2CH'CH,

-OR (91)

and the relative proportions of the two sulphide products correlate well with known SN2 substrate reactivity in methyl and ally1 systems. Nucleophilic attack at sulphur is observed 74 in the reaction of phosphites with ma-dichlorosulphenyl chlorides to give the thiophosphates (92). A new class of stable phosphoranes [e.g. (93)] has been prepared by the

(92)

+

R2C1

CF3 (93)

0 II (RO),P-S -C(CF,)=C(CF,)SMe (943

reaction of small-ring phosphines and phosphites with 3,4-bis(trifluoromethyl)-1,2-dithietan.75 The analogous compounds derived from acyclic phosphites were much less stable and decomposed at room temperature to give cis- and trans-vinyl thiophosphates (94). Attack on Halogen. The reaction of arylhalogenoacetylenes with phosphites has been independently studied by two groups of worker^,^^^ 77 with largely confirmatory results. A kinetic study 76 shows that the reaction is first-order in each reagent and has only a small halogen effect (e.g. kCl/kBr= 1.25). Simpson and Burt 77 have studied the reaction in various mole ratios of alcohol, which should suppress any reactions involving initial attack at halogen. Surprisingly, the maximum amount of phenylacetylene (which is the final product of attack on halogen in alcohol) was 74 76 76

77

W. G. Phillips and K. W. Ratts, J. Org. Chem., 1972, 37, 1526. N. J. De'ath and D. B. Denney, J.C.S. Chem. Comm., 1972, 395. S. I. Miller and A. Fujii, J. Amer. Chem. SOC., 1971, 93, 3694. P. Simpson and D. W. Burt, J. G e m . Soc. (C), 1971, 2872.

108

Organophosphorus Chemistry

similar for both the chloro- and bromo-acetylenes, although the results of Miller and Fuji 76 do not confirm this. However, both groups of workers suggest that two mechanisms are operating simultaneously, the major one being attack on halogen to give the ion-pair (95) and the minor one involving attack on the halogen-carrying carbon. Both mechanisms lead to the same intermediate (96), which gives the isolated phosphonate by an Arbusov reaction. ArCrCX

+

1

(EtO),P

J.

t

A r - C f C - XP(OEt),

+

+

Ar.C-C.P(OEt),

Ar -C=C * P(OEt ),

+

EtX

The reaction of triethyl phosphite with the acetal of l-bromopropionaldehyde to give the vinylphosphonate (97) has been reported.'* The mechanism is thought to involve initial conversion into the vinyl ether (98) followed by attack of phosphite on halogen. A similar reaction with 1 -bromopropionaldehyde gives the phosphate (99). MeCHBr-CH(OEt),

-

MeCBr=CH*OEt (98)

i

(ElO),P

0

II (EtO),P.CMe=CHOEt (97) 0

MeCHBr CHO

'*

+

(EtO),P

L. Reichel and H. J. Jahs, Annalen,

I1

___f

MeCH=CH*OP(OEth

(99)

+ EtBr 1971, 751, 69.

109 The first isolation of an intermediate from the bromination of a phosphite has been achieved with the cyclic phosphite (100). N.m.r. and conductance studies on the reaction mixture kept at 0 "Csupport structure (101) for the intermediate, which on warming to room temperature gives the Arbusov pro duct (1 02). Tervalent Phosphorus Acids

\

Me

+

Br2

MeCN occ

+

BrP(OCH,),Me

CH,Br

The reaction of phosphorous esters and amides with polyhalogenomethanes has been studied and used in a synthesis of phosphates.81 The reaction of diphenyl phosphorochloridate (103), produced in situ from diphenyl phosphonate and carbon tetrachloride, has been studied with various diamines.8 2

A new route to monoalkyl phosphates, using ethylthio protecting groups (104) and reaction with iodine, has been described.83 Electrophilic Reactions.-The biphosphi tes (105) undergo alcohol exchanges4 to give the phosphites (106) and (107), the latter existing in equilibrium with the spirophosphorane (108). The reaction of dialkyl phosphonates with aliphatic diols has been used to prepare polymers, but only when the hydroxy-groups are separated by more than six carbon 78

82

83 84

G . K. McEwen and J. G . Verkade, Chem. Comm., 1971,668. V. S . Abramov N. A. Il'ina, Zhur. obshchei Khim., 1971,41, 100 (Chem. Abs., 1971,75,

20 525). R. P. Napier and S. T. D. Gough, Org. Prep. Proced. Znternat., 1971, 3 , 117 (Chern. Abs., 1971, 75, 62 644). R. S. Edmundson, J. Chem. SOC.( C ) , 1971, 3614. H. Takaku and Y Shimada, Tetrahedron Letters, 1972, 411. R. Burgada, H. Germa, M. Willson, and F. Mathis, Tetrahedron, 1971, 27, 5833.

110

Organophosphorus Chemistry

(108)

Dialkyl phosphonates react 86 with cholesterol under neutral conditions to give the expected phosphonate (109), but in the presence of acid the methyl ether (1 10) is formed. A mechanism involving attack of the alcohol on the protonated phosphonate (1 11) is proposed. The reaction could only be applied to the phenylation of steroids capable of producing homoallylic cations. The reactions of dimethylhalogenophosphineswith methanol and methyl mercaptan have been studied in detail.*' The novel heterocycle (1 13) has

0

II

(109) R

=

R

=

(110)

HP I OMe Me

OH It MeOPOMe I H ( 1 11) 85

87

W. Vogt and S. Balasubramanian, Angew. Chem. Internut. Edn., 1972, 11, 341. Y. Kashman, J . Org. Chem., 1972, 31, 912. F. Seel and K. D. Velleman, Chem. Ber., 1972, 105, 406; F. Seel, W. Gombler, and K. D. Velleman, Annulen, 1972, 756, 181.

Tervalent Phosphorus Acids

111

been obtainedss as a minor product from the reaction of phosphorus tribromide with the acetylenic alcohol (1 12). The reaction of phosphorus trichloride or tris(dimethy1amino)phosphine with carboxylic acid hydrazides gives 89 spirophosphoranes (1 14). Me,C.C-C.CH(OH)*CMe,

+

PBr,

Br-P-0 I

R'

+

R'.CO*NH*NH2 R2,P

HN-P'.

. .

N I'H

Two new olefin syntheses have been developed by Kuwajima and his co-workers. The reaction of the hydroxy-sulphide or sulphoxide 91 with o-phenylenephosphorochloridategives the corresponding ester (1 1 3 , which rapidly decomposes to give the olefin in high yield. The method overcomes the usual problem of removing the sulphur residue. Y-CH2CPh2 + I OH Y = PhS or PhS

II 0

CHz=CPhZ

(1 15)

88 89

B1

R. S. Macomber, J. Org. Chem., 1971, 36, 2713. A. Schmidpeter and J. Luber, Angew. Chem. Internat. Edn., 1972, 11, 306. I. Kuwajima, S.-J. Sato, and Y. Kurata, Tetrahedron Letters, 1972, 737. I. Kuwajima and M. Uchida, Tetrahedron Letters, 1972, 649.

112

Organophosphorus Chemistry

The oxidation of phosphites with methyl phenyl sulphoxide has been in~estigated.~~ Triphenyl phosphite gives the phosphate, while alkyl phosphites rearrange to phosphonates. The oxidation is thought to involve attack of oxygen on phosphorus to give (1 16), whereas the rearrangement probably goes via the sulphonium intermediate (1 17).

Rearrangements.-Boron trifluoride catalyses the rearrangement of unco-ordinated trimethyl phosphite to dimethyl methylphosphonate, but reacts quite differently with co-ordinated phosphite to give complexes with fluorophosphine ligands.93 The phosphoramidite (1 19) has been isolated 94 from a low-temperature reaction of phenyl isocyanate with (1 18), which normally gives the phosphonate (120). A kinetic study suggests the mechanism shown for the rearrangement of (1 19) to (120). (EtO),PNHPh

+

PhNCO ---+

(EtO),PNPhCONHPh

( I 18)

0

II ?(EtO),p-C: ( 1 20) 02 Q3 O4

I1

( 1 19)

m

NPh

( EtO)23/

NHPh

PhN=C 0 P(OEt), /

PhN H

\F=NPh YHP”

o\’

S. Oae, A. Nakanishi, and S. Kozuka, Tetrahedron, 1972, 28, 549. B. Demersemen, G. Bouquet, and M. Bigorgne, J. Organometallic Chem., 1972,35, 125. R. F. Hudson and A. Mancuso, Tetrahedron Letters, 1971, 3821.

113

Tervalent Phosphorus Acids

Cyclic Esters of Phosphorous Acid.-The conforinational analysis of a number of 2-substituted-2-phospha-1,3-dithiacyclohexanes (121)and (122) has been carried The free energy for cis-trans equilibrium in (121) was determined, and although n.m.r. showed that the tertiary butyl group Me

was equatorial it was not possible to determine the configuration at phosphorus. The axial preference for the phosphorus substituent in (122) was shown for all the groups studied except tertiary butyl, where the severe steric interaction may cause either a preferred equatorial orientation or the existence of a single twist conformation. The cis-trans isomerization of 4-methyl-2-oxo-2H-l,3,2-dioxaphosphorinans (123) and (124) has been studied by lH n.m.r. spectroscopy on a sample of 90% trans-pho~phorinan.~~ The reaction is first-order, with an activation energy lower than the inversion barrier in tertiary phosphines. In view of this, a mechanism involving deprotonation and inversion of the phosphite anion is proposed. 0

II

H M z z P \I o

A

M=2p\H ( 124)

( 1 23)

Me

0

II

R P -0CH2CMe, C H 2 0H H (125)

( 126)

A variable-temperature n.m.r. study O7 of 2-substituted-5,5-dimethyl1,3,2-dioxaphosphorinans(1 25) suggests a predominance of one conformer at room temperature. The secondary phosphinite (126) is obtained from the neutral hydrolysis of (1 25). The thermal stability of the cyclic phosphites (127) is reported0* to depend on the orientation of the tertiary butoxy-group. Cyclic esters of the type (128) are surprisingly inert to protic acid reagents compared with their acyclic analogue^.^^ The results are explained in terms of ring strain (cf. refs. 59 and 60). 95 ST

9B

R. 0. Hutchins and B. E. Maryanoff, J . Amer. Chem. SOC.,1972, 94, 3266 E. E. Nifant’ev and A. A. Borisenko, Tetrahedron Letters, 1972, 309. D. W. White, Phosphorus, 1971, 1, 33. A. A. Borisenko and E. E. Nifant’ev, Zhur. obshchei Khim., 1970,40,2765 (Chem. Abs., 1971, 74, 140 742). J. Mikolajczyk, J. Michalski, and A. Zwierzak, Chem. Comm., 1971, 1257.

114

Organophosphorus Chemistry

Miscellaneous Reactions.-Phosphinites are reported to form 2 :1 complexes with tin halides.loO Mercuric chloride initiates the formation of the novel betaine (129) from dialkyl phosphonates and pyridine.lol The betaine is useful in synthesis since treatment with alcohols or amines

-0-P-CI

Q

-0-i-OR2

R'O

I

/ \

OR'

I

-o-P-NHR~ / \ R'O OR'

R3C0,H

I

R3C0,R2

R3C0,H

R3CONHR2

followed by reaction with carboxylic acids provides a high-yield route to esters and amides. The thermally induced polymerization of the mixed anhydrides (1 30) has been investigated.lo2 A variety of hypodiphosphites [e.g. (13 1) ] has been

To\

(CH,),

POCO-Me

LOJ ( 130) 100

lol

l02

A. N. Pudovik, A. A. Muratova, M. D. Medvedeva, and E. G . Yarkova, Zhur. obshchei Khim., 1971, 41, 766 (Chem. Abs., 1971, 75, 49 254); A. N. Pudovik, A. A. Muratova, E. G . Yarkova, and M. D. Medredeva, Zhur. obshchei Khim., 1971, 41, 1481 (Chem. Abs., 1971, 75, 129 888). N. Yamazaki and F. Higashi, Tetrahedron Letters, 1972, 415. A. Munoz, M. T. Boisdon, and R. Wolf, Conipt. rend., 1971, 272, C, 1161.

Tervalent Phosphorus Acids a o \ P C l / 0’

+ Na

-

115

(131)

prepared from the reaction of the corresponding phosphorochloridite with sodium, and their reactions have been studied.lo3 3 Phosphonous and Phosphinous Acids and their Derivatives The rate of hydrolysis of 1-phenylethyl phenylphosphinate (132) as a function of pH has been investigated.lo4 Generally the rate increases with pH, but remains constant below pH7. This is attributed to the existence ~ at low pH, and a p value of -4.25 for 1-arylethyl of an S N mechanism 0 II HPOCHMePh

OH

I

P

/ \

I Ph

Ph OCHMePh

1-:

( 132)

( 1 33)

0

II

HPOH Ph

phenylphosphinates supports this. An alternative to the normal alkaline hydrolysis mechanism is also presented. Slow equilibration with the tervalent species (133), followed by rapid hydrolysis, would give the expected product (presumably there is a mistake in the original paper, which refers to the second step as slow). Some support for this mechanism R,PCI(CO),MO

H,O E[,N

’ RzPOH I

‘y(

Mo(C0)5

134)

l0s

E. E. Nifant’ev, A. I. Zavalishina, and I. V. Komlev, Zhur. obshchei Khim., 1971, 41, 1451 (Chem. Abs., 1971, 75, 140 806). D. S. Noyce and J. A. Virgilio, J. Org. Chem., 1972, 37, 1052.

116

Organophosphorus Chemistry

is available from the high rate of hydrolysis of triethyl phosphite compared with diethyl phosphonate. The first examples of the tervalent tautomer of phosphinous acids have been prepared as transition-metal complexes (134). The structures were assigned on the basis of distinctive spectral evidence and reactions with diazomethane and triethylamine to give (1 35) and (136) respe~tive1y.l~~ Io6

C. S. Kraihanzel and C. M. Bartish, J. Amer. Chem. Soc., 1972, 94, 3572.

6

Q u i nq uevalent Phosphorus Acids ~

~

~~

BY N. K. HAMER

1 Phosphoric Acid and its Derivatives Synthetic Methods.-The preparation of phosphate esters by s N 2 attack of phosphate ester anions on carbon is receiving more attention following the realization that the poor nucleophilicity commonly associated with such anions is due to solvation and ion-pairing effects. Thus tetramethylammonium di-t-butyl phosphate reacts with primary and secondary alkyl iodides in aprotic solvents to give the corresponding triesters (1) from which the t-butyl groups are readily removed by trifluoracetic acid.l The proposal of a similar SN2mechanism in the reaction of triphenylphosphine and ethyl azodicarboxylate with a phosphate diester in the presence of an (But0)2P02-

+

N+CH,

NH,

RI

-

ROPO(OBut),

Br

(1)

H+ d

ROP03H,

H,O I

NHz

alcohol has received support from the finding that octan-2-01 is converted into the phosphate triester with inversion of configuration.2 With the very reactive halide (2), mere aqueous solvolysis in the presence of a high concentration of inorganic phosphate (or pyrophosphate) gave useful conversion to the phosphate (or pyrophosphate) e ~ t e r . ~ Phosphorylation procedures using activated phosphate esters continue to be developed and esters of the type (3) may be conveniently prepared from monoalkyl phosphates and imidazole (or 2-hydroxypyridine) using bis-(2-pyridyl) disulphide and triphenylph~sphine.~ p-Nitrophenyl phosphate (4) and its symmetrical pyrophosphate ( 5 ) have been found to phosphorylate alcohols in the presence of pyridine and it is probable that A. Zwierak and K. Kluba, Tetrahedron, 1971, 21, 3163. 0. Mitsunobu and M. Eguchi, Bull. Chem. SOC.Japan, 1971,44, 3427. G. M. Brown, Methods Enzymol. (A), 1970, 18, 162. T. Mukaiyama and M. Hashimoto, Bull. Chem. Sac. Japan, 1971, 44, 2284. K. J. Chong and T. Hata, Bull. Chem. SOC.Japan, 1971, 44, 2741. 5 117

118

Organophosphorus Chemistry

OH

I

OH

(5)

OH

0 -0,II -O/P--NQ

+NMe

an N-phosphorylated pyridine is an intermediate. The N-phosphorylimidazolium salts (6) (from the parent base and phosphoryl chloride) appears to be a useful phosphorylating agent for amines in aqueous solution.6 The use of phosphoryl and pyrophosphoryl chlorides has been extended and full details of the scope of o-phenylene phosphorochloridate have appeared.8 Alkyl dimethyl phosphates are converted into the corresponding alkyl phosphorodichloridates by reaction with thionyl chloride in the presence of tetraethylammonium chloride (Scheme l ) . O ROPO(OMe)n

+

Mc,NCI

SOCI, A ROPOCI, Scheme 1

Oxidation of hypophosphorous acid with carbon tetrachloride and triethylamine at 90 "C in the presence of an alcohol gives dialkyl phosphates (Scheme 2).1° Monoalkyl phosphites can be converted into H3PO2

lo

+

ROH

+

Et,N

CCld 6 (R0)2PO,H Scheme 2

E. Guibe-Jampel, M. Wakselman, and M. Vilkas, Bull. Soc. chim. France, 1971, 1308. R. J. W. Cremlyn, B. B. Dewhurst, and D. H. Wakeford, Synthesis, 1971, 648. T. A. Khwaja and C. B. Reese, Tetrahedron, 1971, 21, 6189. T. H. Colby, G.P. 2 140 298 (Chem. Abs., 1972, 76, 112 679). E. E. Nifantev, V. S. Blagoveshchenskii,A. M. Sokurenko, and L. S. Skylarskii, Zhur. obshchei Khim., 1971, 41, 1644.

Quinquevalent Phosphor us A cids

119

mixed phosphate diesters under similar conditions, but phosphorous acid itself does not react. Oxidation of the fairly accessible OSS-triesters (7) of phosphorodithious acid with aqueous iodine has been proposedll as an additional route to monoalkyl phosphates. An active phosphorylating species (probably the N-phosphorylquinonimine) is formed when the aminophenol derivative (8) is oxidized with bromine.12 Further examples of oxidative phosphorylation with inorganic phosphate when the thioethers ROP(SEt), ( 7)

I,-H,O

ROP03H2 SMe

OH (9)

(10)

(11)

or thioesters (9)-(11) are oxidized by bromine in the presence of pyridine have been described.13 Preparative studies have been reported on the phosphorylation of a series of hydrazines and hydrazones14 and on the phosphorylation of vicinal diamines with diphenyl phosphor~chloridate.~~ The cyclic phosphoramidate esters (12) and (13) may be obtained by treatment of the appropriate acyclic 0

II

R'O-P-NHR2 I O(CH,), X (14)

O ; CNl

R1

l1

l2 l3

l4

l5

H. Takaku and Y. Shimada, Tetrahedron Letters, 1972, 41 1. E. Ohtsuka, S. Morioka, and M. Ikehara, Tetrahedron Letters, 1972, 2553. E. Bauerlein and T. Wieland, Angew. Chem. Znternat. Edn., 1971, 10, 541. R. J. W. Cremlyn, B. B. Dewhurst, and D. H. Wakeford, J . Chem. SOC.( C ) , 1971,301 1. R. S. Edmunsdon, J. Chem. SOC.(C),1971, 3614.

120

Organophosphorus Chemistry (EtO),PONH,

Hr,

K,CO,~(Et0)2PONBr, (15)

precursor (14) with sodium hydride.16 Diethyl NN-dibromophosphoramidate (15) has been prepared l7 and shown to add to olefins in the expected manner. Attention has been drawn to the danger of explosion in the reaction of dimethyl phosphoramidate with chlorine on a large scale.l* A novel procedure has been developed for the synthesis of phosphate esters of hindered alcohols, and was designed to avoid nucleophilic displacement reactions. It involves photolysis of the alkyl nitrite in the presence of a trialkyl phosphite and proceeds by addition of the alkoxyl radical to phosphorus followed by elimination of an alkyl group (Scheme 3).19

(RZO), PO(OR1) Scheme 3

Diethyl trichloromethylphosphonate (1 6 ) reacts with ribonucleotides, and presumably with other vicinal 1,2-diols, in the presence of triethylamine 2o to give a mixture of the 2’- and 3’-phosphates. The readily available a-hydroxyphosphonate esters (17) rearrange in base to the phosphate C;‘H,OH

CH,OH

HO- P=o I OEt Ar2C-PO(OR)2 I OH (17) l7

l8 lQ

2o

+

2’-isomer

base

+ Ar2CHOPO(OR),

D. Savignac, M. Dreux, and J. Chenault, Compt. rend., 1971, 272, C , 2189. A. Zwierak and S. Zawadzki, Synthesis, 1971, 323. H. D . Block and R. Schliebs, Angew. Chem. Internat. Edn., 1971, 10, 491. D. H. R. Barton, T. J. Bentley, R. H. Hesse, F. Mutterer, and M. M. Pechet, Chem. Comm., 1971, 912. A. Holy, Tetrahedron Letters, 1972, 157.

121

Quinquevalent Phosphorus Acids

triesters and have thus been used in the preparation of substituted benzhydryl phosphates.21 Protection of a phosphate as its 2-phenylthioethyl ester has been shown to be a useful method in the syntheses of phosphate diesters in the nucleotide field.22 This protecting group is fairly stable to acid and base but treatment with periodate converts it into the sulphoxide (18), which undergoes rapid elimination in aqueous base (Scheme 4). R’OP03H2

+

PhSCH,CH,OH

DCC

0 II R1O- P-OCHZCH,SPh I OH

I

ArS0,CI R 2 0 H

H 0 I P-O-CH,-C-SO*Ph PO’
R’O,I

0

HIO,

0 II R’O-P-OCH,CH,SPh I OR2

Scheme 4

Solvolyses of Phosphoric Acid Derivatives.-The solvolysis of organic phosphates has been reviewed.23 A significant lSO isotope effect was observed in the solvolysis of the dianion of 2,4-dinitrophenyl phosphate, and since no such isotope effect is observed in the alkaline solvolysis of the dibenzyl ester this has been adduced as evidence for a monomeric metaphosphate elimination in the former case.24 The nucleophilic attack of hydroxide ion on bis-(2,4-dinitrophenyl) phosphate is inhibited by micelles of non-anionic detergents and this is attributed to binding of the Hydrolysis of 3,4-dimethoxyphenyl phosphate proceeds by way of the monoanion, the neutral molecule, and the conjugate acid, and is thus in accord with earlier results on other methoxyphenyl phosphates.26 21 22

23 24 25 26

H. Timmler and K. Kurz, Chem. Ber., 1971,104, 3740. R. H. Wightman, S. A. Narang, and K. Itakura, Canad. J. Chem., 1972, 50,456. Y. Murakami and J. Sunamoto, Kagaku No Ryoiki, 1971, 25, 989 (Chem. Abs., 1972, 76, 2979). D. G. Gorenstein, J. Amer. Chem. SOC., 1972, 94, 2523. C. A. Bunton, A. Kamego, and L. Sepulveda, J. Org. Chem., 1971, 36, 2566. M. Mhala and S . Prabha, Indian J. Chem., 1970, 8, 972.

122

Organophosphorus Chemistry

Rates of solvolysis of phenyl and methyl polyphosphates in water and alcohols have been measured and the reasons for the enhanced reactivity From of the former relative to the phenyl phosphorochloridate studies on a series of substituted aryl sulphatophosphates (19) it was 0 0 I1 II ArO-P-0-S-OH I I OH OH (19)

+

concluded from the p value of 0.22 28 and the solvent isotope effect that in acidic conditions hydrolysis proceeded by an A 1 mechanism, whereas in alkaline solution ( p = 0.67) bimolecular attack on phosphorus occurs. Several studies on intramolecular catalysis of the solvolysis of phosphate esters have been reported. The larger hydrolysis rate of the zwitterion of 8-hydroxyquinoline phosphate (20) compared with that of pyridyl 3-phosphate (21) was a t t r i b ~ t e d ,on ~ ~ the basis of the kinetic isotope effect, to intramolecular general acid catalysis. A similar general acid catalysis by the hydroxy-group seems to operate in the (3-hydroxy-2pyridy1)methyl phosphate dianion (22),30 which hydrolyses faster than either the monoanion or the neutral molecule. From a study of 4- and 5-substituted derivatives of salicyl phosphate (23) it is suggested 31 that the negligible solvent isotope effect is inconsistent with preliminary proton transfer, and that here also intramolecular general acid catalysis by the

+

I 00 II ,oD

27 28 29

30

H. Berger, 2. Naturforsch., 1971, 26b, 694. W. Tagaki, T. Eiki, and I. Tana, Bull. Chem. SOC.Japan, 1971, 44, 1139. Y . Murakami and J. Sunamoto, Bull. Chem. SOC.Japan, 1971, 44, 1939. Y . Murakami, J. Sunamoto, and H. Ishizo, Bull. Chem. SOC.Japan, 1972, 45, 590. R. H. Bromilow and A. J. Kirby, J . C . S . Perkin II, 1972, 123.

Quinquevalent Phosphorus Acids 123 carboxy-group (which also catalyses the reactions with other nucleophiles) operates. In contrast the carboxy-group participates as a nucleophile in the solvolysis of the mixed phenyl aryl esters (24),32in which the initial attack may be followed by formation of the phthalic anhydride. From these studies it was concluded that a quinquecovalent intermediate (25) was formed from which the best leaving group was expelled, implying that (25) undergoes pseudorotation faster than breakdown (Scheme 5).

0-

Scheme 5

The role of zinc ions as catalysts for phosphoryl transfer between phosphorimidazole and pyridine-2-carboxaldoxime is attributed 33 to a lowering of the electrostatic barrier for attack of the anion of (26) on phosphorus; it may also act as a template for the proper alignment of the entering and leaving groups. With amine nucleophiles it was found that zinc, in common with several bivalent cations, inhibited attack on phosphorimidazole. se 98

R. H. Bromilow, S. A. Khan, and A. J. Kirby, J . C. S. Perkin II, 1972, 911. G. J. Lloyd and B. S . Cooperman, J. Amer. Chem. Soc., 1971, 93, 4883, 4889.

124

Organophosphorus Chemistry

OS-Dimethyl phosphoramidothioate (27) shows unexpected solvolytic behaviour in base,34since reaction with hydroxide leads mainly to P-0 cleavage whereas with alkoxides P- S cleavage predominates. For the NN-dimethyl derivative not only is hydroxide attack much slower but in contrast gives exclusive P-S cleavage. On this basis it was suggested that under strongly basic conditions (27) solvolyses by way of a metaphosphorimidate intermediate resulting from P- S cleavage (Scheme 6). With

MeO-P, 40 N €4

Scheme 6

milder basic conditions an S N 2 displacement of methoxide ion assisted by intramolecular proton transfer was proposed. The solvolysis of the phosphorylated aldoxime (28) is subject to general base catalysis, but proceeds by elimination rather than attack at 0

B:' (28) 34

M. H. Fahmy, A. Khasawinah, and T. R. Fukuto, J . O r g . Chern., 1972, 37, 617.

125

Quinquevalent Phosphorus Acids

p h o ~ p h o r u s .Similarly, ~~ the fully esterified O-phosphorylated benzamidoxime (29), unlike the phosphonate and phosphinate analogues (see later), undergoes a base-catalysed elimination accompanied by rearrangement to N-phenylcyanamide (Scheme 7).36 c , N -0 P O ( 0 P r 1 Ph-CC \N-H

I

(29) H%H

I

d PhN=C=NH

+

(Pri0)2P02-

PhNHCN Scheme 7

Monoanions of N-substituted phosphoramidic acids (30) show an interesting solvolytic rate dependence on the basicity of the amir~e.~’For amines of p K , < 8.0 the rate is independent of basicity, and for these cases it was suggested that the fraction of N-protonated species became rate limiting. From a comparison of the Bronsted /3 values associated with the entering and leaving groups it was proposed that quinquecovalent intermediates are not involved in the solvolysis of (30) or in the solvolysis

(30)

(31) R1,R2,R3 = H or alkyl

of mono- or di-esters of phosphoric acids. The hydrolysis and reactions of orthophosphoric amides have been reviewed 38 and studies reported on the solvolysis of diethyl phosphorimidazole in water and alcohols.39 From investigations on the alkaline solvolysis of fully esterified derivatives of phosphocreatinine (31) and related compounds it was concluded 40 that the ring size did not greatly affect the rate compared with acyclic analogues, but that the presence of N-alkyl groups in the ring did, implying that tautomerism may be important. Substituted styryl diethylphosphates (32) undergo acid-catalysed hydrolysis by an AsE2 mechanism (Scheme 8), the rates correlating with (T+ and p = - 2.1.41 Using l*O-labelled substrate it was established that 35

36

37

38 38 40

41

G. Zimmer and A. Scherer, Arch. Pharm., 1971,304,498 (Chem. Abs., 1971,75,97 920). R. F. Hudson and R. Woodcock, Chem. Comm., 1971, 1050. S. J. Benkovic and E. J. Sampson, J . Amer. Chem. SOC.,1971, 93, 4009. N. N. Preobrazhensjkaya, Uspekhi Khim., 1972, 41, 96 (Chem. Abs., 1972,76, 98 544). E. V. Degterev and L. Nikolenko, Zhur. obshchei Khim., 1970, 40, 2762. M. P. Alimov, V. E. Belskii, and P. I. Alimov, Zhur. obshchei Khim., 1971, 41, 1789. R. D. Frampton, T. T. Tidwell, and V. A. Young, J. Amer. Chem. Soc., 1972,94, 1271.

126

Organophosphorus Chemistry Ar_+ *OPO(OEt),

ArCOCH,

+

(Eto) POzH Scheme 8

exclusive C - 0 cleavage unlike the corresponding carbonate esters where both A s ~ and 2 A ~ c mechanisms 2 operate. Reactions.-The thermal decomposition of phosphorylated hydroperoxides (33) and (34) has been studied and found to proceed by two mechanisms: a radical mechanism involving fission of the 0-0 bond which is observed in non-polar solvents, and an ionic mechanism involving rearrangement which is favoured by polar 44 The latter reaction is observed in (34) even at -60 "C,owing to the high migratory aptitude of the phenyl group. Irradiation of the disulphide analogue (35) results in homolytic cleavage of the S- S bond and leads, in the presence of acetylene, to the vinyl ester (36).45

(35)

(36)

Tetramethylammonium dimethyl phosphate reacts with a-bromoketones in aprotic solvents to give a mixture of products resulting from &2 substitution and elimination, the relative proportions depending on the structure of the ketone.46 a-Bromoaldehydes (37) gave similar produ~ts,~' KCHBr-CHO

0 II /O\ > II-CH-CH-O-P(OMe),

( McO)~PO,-

R-CH-CHO I

(37)

42

43 44

45

46

47

E. P. Lyznicki and T. T. Tidwell, J . Amer. Chem. SOC.,1972, 94, 3676. V. P. Maslennikov, V. P. Sergeeva, and V. A. Shushunov, Kinetika i Kataliz, 1971,12, 575 (Chem. Abs., 1971, 75, 87 912). V. P. Maslennikov and V. P. Sergeeva, Zhur. obshchei Khim., 1970, 40, 2529; Zhur. org. Khim., 1971, 7, 686 (Chem. Abs., 1971, 75, 36242). A. A. Oswald and J. H. Lesser, G.P. 2 032 494 (Chem. Abs. 1971, 74, 124 915). J. Kraus and G. Sturtz, Bull. SOC.chim. France, 1971, 2551, 4006. A, Raphael and G . Sturtz, Bull. SOC.chim. France, 1971, 2962.

127

Quinquevalent Phosphorus Acids

but it is possible here that the epoxy-phosphate esters (38) may be involved as intermediates. At 600 "C in the vapour phase the aryl phosphorodichloridate (39) cyclizes to (40).48 The reaction of dimethyl phosphorochloridate with aniline in nitrobenzene appears to be catalysed by both the reactants and the When the phosphorimidic chloride (41) was treated with

600 "C

O=PO CI,

-

'P-0

4\

0 CI

CI3C.CC1,. N=PCl,

R,NCN

+

Me,NC H 0

Me,NCH=NPOCI,

(43) PCI,

so

R,N-C=NPCI,

(44)

/

c1

R2N, ,C=NPOCI,

c1

(45)

sulphur dioxide (or formic acid) it gave N-dichloromethylenephosphoramidic dichloride (42).50 The related phosphorimidic chloride (43) was found to react with DMF to give the products (44).61Dialkylcyanamides react with phosphorus pentachloride to give, after treatment with sulphur dioxide, the phosphorami dic dichloride (45). HMPT reacts with benzylic halides at reflux temperatures to give NN-dimethylben~ylamines.~~ A 3 :l-adduct is formed from HMPT and terephthaloyl chloride, for which the structure (46) has been 0

0

(Me,N) % - ~ - - C O ~ C O - h !(NMe,),,( Me,N),P=O M e2 Me, 2 c1(46)

48 48

50

61 62

E. A. Chernyshev, E. F. Bugerenko, and V. I. Aksenov, U.S.S.R.P.289 905 (Chem. Abs., 1971, 75, 6089). V. A. Savelova, L. M. Litvinenko, and L. A. Baranovskii, Zhur. org. Khim., 1972, 8, 89 (Chem. A h . , 1972, 76, 112 300). E. S. Kozlov and B. S. Drach, Metody Poluch. Khim. Reaktivov Prep., 1969, 80 (Chem. Abs., 1971, 75, 129 301). V. P. Kukhin, Y. Y . Semenii, and A. V. Kirsanov, Zhur. obshchei Khim., 1971,41,1459. I. M. Kosinkaya, A. M. Pinchuk, and V. I. Shevchenko, Zhur. obshchei Khim., 1971, 41, 2396.

63 54

R. S. Monson and N. Degarry, Chem. Comm.,1971, 1018. T. Rue11 and G. Le Strat, Compt. rend., 1971, 273, C, 1384.

128

Organophosphorus Chemistry

Oxidation of the cyclic selenophosphate ester (47) with both dinitrogen tetroxide or nitric acid appears to be very stereoselective, proceeding with retention of config~ration,~~ and thus contrasts with the behaviour of similar acyclic phosphorothioates and phosphonothioates with these reagents. Heterocyclic N-oxides and the 1 -aminopyridine derivative (48)

\

OMe

OMe

(RO), Pr

Se Se 14

CI,

----+

(RO),PC

Se SeCl

(51)

are reduced by 00-dialkyl phosphorodithioic acids to give (49), but the details of the mechanism including the position of initial attack have not yet been ~ l a r i f i e d . ~The ~ diseleno-analogues are oxidized to (50) by chlorine, but only to the dimer (51) by iodine.57 0-Alkyl phosphorotrithioate salts are converted by treatment with hydrogen chloride and a dihydric phenol into the mixed esters (52).58 Structure (53) has been proposed for the product from reaction of phosphorus pentasulphide with the thiophen derivative (54).59 Studies on the

ROPS3'-

+

HO SH (52)

55 56 57 68

W. Stec, A. Okruszek, and J. Michalski, Angew. Chem. Internat. Edn., 1971, 10, 494. S. Oae, A. Nakanishi, and N. Tsujimoto, Tetrahedron, 1972, 28, 2981. R. D. Gorak and N. I. Zemlyanskii, Zhur. obshchei Khim., 1971, 41, 1994. N. A. Kolesnikova, N. I. Zemlyanskii, and B. P. Kotovich Zhur. obshchei Khim., 1971, 41, 1434.

59

J. Brelivet, P. Apprion, and J. Teste, Bull. Soc. chim. France, 1971, 1344.

Quinquevalent Phosphorus Acids

129

thermal decomposition of metal salts of 00-dialkyl phosphorodithioic acids have been reported.s0 2 Phosphonic and Phosphinic Acids and Derivatives

Synthetic Methods.-There have been conflicting reports in the past concerning the nature of the products from reaction of phosphorus trichloride with olefins in the presence of oxygen. In a careful study with vinyl chloride as the olefin it has been shown that both the phosphonoand phosphoro-dichloridates ( 5 5 ) and (56) are formed.61 On the other CH,=CHCI

+

PCI,

O2

CH,CI~CHCI.POCI,

+

CH,CICHCI-OPOCI,

(54)

(55)

+

j

PO ( O m ,

(59)

hand, cyclohexene gives only the phosphonic acid derivatives (57), (58), and (59).62 It seems likely that the products of this type of reaction may be sensitive to both the conditions and the structure of the olefin. Pyrylium phosphonic acids (60a) have been prepared by the reaction of triethyl phosphite with pyrylium salts followed by oxidation of the product (either before or after hydrolysis) with the triphenylmethyl carbonium ion? This approach has been used to obtain the analogous thiopyrylium phosphonates (60b) and the cyclopropene and tropylidene derivatives (61) and (62).64 The enamine phosphonates (63) are readily accessible from addition 61 62

63

84

B. E. M. Hassan, Chem. Tech. (Leipzig), 1971,23,540 (Chem. A h . , 1971,75, 117 829). C. B. C. Boyce and S. B. Webb, J . Chem. Soc. (C), 1971, 3987. 0. Chikamune, Y. Okamoto, and H. Sakura, Kogyo Kagaku Zasshi, 1971, 74, 132 (Chem. A h . , 1971, 74, 125 800). P. F. Vaziyanova, S. N. Baranov, and S. K. Krivin Zhur. obshchei Khim., 1970,40,1904. S . K. Krivin, 0. F. Moskova, and S. N. Baranov, Zhur. obshchei Khirn., 1972, 42, 58.

130

Organophosphorus Chemistry (Et 01,P =o

(E tO)2P=0

i

I

(a)

x

(h) X

= =

0 S

(60)

R’C =C-PO(OR’)2

R’C-C-NR22

+

It’,

R2,NH

R2?N

,C=CH-PO(OR’),

40

(R30)?P,

(65)

R’CH=C,

H

,N R2* PO(OR~)~ (64)

of the secondary amines to the appropriate acetylenic p h o ~ p h o n a t e sand ,~~ the isomeric analogues (64) may be synthesized by reaction of the ynamines (65) with dialkyl phosphites.66 Arylphosphonic acid esters are produced in the reaction of diary1 iodonium salts with trialkyl phosphites in the presence of copper but despite the simplicity of the procedure yields are low owing to side reactions. The cyclic bisarylphosphinic acid (66) is conveniently prepared by fusion of the phosphine oxide (67) with sodium hydroxide.68 A successful

Ph

Ph

66 66

67 68

‘OEt

Ph

M. S. Chatta and A. Aguiar, J. Org. Chem., 1971, 36, 2892. N. Schindler and W. Ploger, Chem. Ber., 1971, 104, 2021. A. G. Varvoglis, Tetrahedron Letters, 1972, 31. J. L. Suggs and L. D. Freedman, J. Org. Chem., 1971, 36, 2566.

131

Quinquevalent Phosphorus Acids

preparation of the monomeric 1 -alkoxyphosphole 1-oxide (68) involves treatment of (69) with N-bromosuccinimide, followed by base.ss Its rate of saponification was found to be very similar to that of (69). Aryl-substituted acetylenic phosphonic acids are formed by reaction of the appropriate acetylene with phosphorus pentachloride, followed by treatment of the initial adduct (70) with base.70 Improved yields of ArCrCH

+

*r\

PCI,

,C=C,

/H

c1

i , Et,N

pc1,

5ArC=CPO(OH), H2O ‘‘7

acetylenic phosphonates from the reaction of a Grignard reagent with a phosphorochloridate are reported when pyridine is present as a catalyst.71 Improvements have been made in the synthetic procedures for a-hydroxyalkyldiphosphonic acids (71),72 and the preparation of dihalogenomethylenediphosphonic acids (73) from reaction of (72) with hypohalite ion has been The latter may be reduced to the monohalogeno-analogues (74) with hydrosulphides. Treatment of amides

CH,(P03H2), (72)

NaOCl

H,N

y

‘IN

CI,C(P03H2), (73)

NaSH

* CICH(P03H,)2 (74)

O,pfio

(‘OH PO(OHl2

with phosphorus trichloride gives the a-aminoalkylphosphonic acids ( 7 3 , which are useful chelation agents; under similar conditions formamide itself gave the product (76).74 68 70

71 72 73

F. B. Clarke and F. H. Westheimer, J. Amer. Chem. Soc., 1971. 93 4541 A. V. Dogadina, Y. D. Nechaev, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1971, 41, 1662. M. S. Chatta and A. M. Aguiar, J . Org. Chem., 1971, 36, 2719, 2720. D. A. Nicholson and H. Vaughn, J. Org. Chem., 1971,36, 3843. D. A. Nicholson and H. Vaughn, J . Org. Chem., 1971,36, 1835. K. Gutzchebauch, K. Wollmann, G.P. 1958 125; K. Wollmann, W. Ploger and K. H. Worms, G.P. 1958 123 (Chem. A h . , 1971,75, 36 333-4).

132

Organophosphorus Chemistry

A simple synthesis of y-aminoalkylphosphonic acids (77) involves addition of a nitroalkane to vinylphosphonic esters, followed by catalytic hydr~genation.~~ p-Aldehydophosphonic acids (78) are conveniently prepared by acidic hydrolysis of the readily accessible #?-alkoxyvinylp h o ~ p h o n a t e s .Oxidation ~~ of (2-pyridy1)methyl phosphonic acid (79) with R1CH=CHPO(OR2),

+

CH,NO,

R20-

--+

I

0,NCH,.CHR'.CH,PO(OR2), H,-Ni

H,NCH,. CHR1-CH,PO(OR2 )2 (77)

OHC. CH,PO(OEt), (78)

I

I

0-

0-

(80)

peracids provides a general route to the appropriate N - o x i d e ~ since , ~ ~ the 2-isomers cannot be prepared by the reaction of diethyl phosphonate anion on the halide (80). Dithiophosphinic acids are produced in good yield by the reaction of the perthiophosphinic anhydride (81) with Grignard reagents.'* Reaction of H,S with compounds containing a P-Cl bond can, in selected cases, provide a convenient route to phosphonothioates. Thus the adduct of acetal and phosphorus pentachloride gives (82) 79 under these conditions, and the cyclic trimeric anhydride (83) is formed from the phosphonic chloride (84).*O

(MeO),CHCH,

i, PCI,

MeOCH=CHPSCI, (82)

75

76 77

78 79

T. A. Mastryukov, M. V. Lazareva, and V. V. Perekalin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 353 (Chem. Abs., 1971, 7 5 , 76947). V. V. Moskva, V. M. Ismailov, and A. I. Razumov, Zhur. obshchei Khim., 1971,41,90. R. Bodalski, M. Pietrusiewicz, P. Majewski, and J. Michalski, Coll. Czech. Chem. Comm., 1971, 36,4079. K. Diemert and W. Kuchen, Angew. Chem. Internat. Edn., 1971, 10, 508. V. V. Moskva, V. M. Ismailov, and A. I. Razumov, Zhur. obshchei Khim., 1970, 40, 1489. A. Ecker and U. Schmidt, Monatsh., 1972, 103, 736.

133

Quinquevalent Phosphorus Acids

CI I

(84)

Useful preparative procedures have been given for the conversion of phosphonic and phosphinic chlorides to amides and hydrazides.81 The reverse reaction also may be useful in synthesis and is best carried out by treating the appropriate amide with hydrogen chloride in an inert solvent. This latter reaction not unexpectedly proceeds with retention of configuration on (85), whereas the acyclic analogues undergo racemization.82

+'

NHCH,Ph

CI

Solvolyses of Phosphonic and Phosphinic Esters.-The alkaline solvolysis of 0-phosphonic and phosphinic esters of benzamidoxime [ (86a) and (86b) ] differs from that of the phosphorylated derivatives. In the case of

Ph (a) R = EtO (b) R = Ph (86)

(86a) there is a rapid loss of ethanol giving an intermediate (87), which is slowly converted into the thermodynamically more stable (88) (Scheme 9). This is attributed 36 to intramolecular nucleophilic attack leading to a cyclic intermediate which opens to give (87). In contrast, the phosphinic ester (86b) undergoes a straightforward hydrolysis. The difference in behaviour of these compared with the phosphate ester (29) is ascribed to the fact that although the phosphonate is more susceptible to nucleophilic attack at phosphorus, the anion is a poorer leaving group than a dialkyl phosphate anion. It was not possible to exclude a similar type of vicinal nucleophilic catalysis in the solvolysis of (89) in the pH range 2-3.5, but in the full paper the authors still prefer an intramolecular general acid catalysis me~hanisrn.~~ 81 82 89

A. F. Grapov, 0. B. Mikhailova, L. V. Razvodovskaya, and L. L. Melnikov, Zhur. obshchei Khim., 1971, 41, 1644. K. Ellis, D. J. H. Smith, and S. Trippett, J. C. S. Perkin I, 1972, 1184. J. I. G. Cadogan, J. A. Challis, and D. T. Eastlick, J. Chem. Soc. (B), 1971, 1988.

134

Organophosphorus Chemistry P 1-1

HNI ,0“ Ph-P-0I

1-

OEt

Ph

EtO-

/

0 II ,N H2 Ph--P-O-N=C I I OH Ph (88) Scheme 9

Imidazole catalyses the hydrolysis of a series of arylphosphinic esters (90) with p = 2.6, compared with the value of 1.5 for attack by hydroxide.** On this basis, together with the solvent isotope effect, a general base-

R3 I

04

H20:/Io\c”N/ / Ar

0 A,.‘

2P‘OAr

catalysed mechanism was proposed although in certain cases nucleophilic catalysis was also important. In contrast, the reaction of a series of hydroxylamine and hydrazine derivatives with g-nitrophenyl methylphosphonate anion 8 5 does, in general, seem to involve nucleophilic attack, for although there is no large a-effect the rates are very sensitive to steric effects. Hydroxylamine itself was anomalously reactive and it was suggested that either 0-attack was occurring or that the formation of the transition state was assisted by hydrogen-bonding. 84 86

A. Williams and R. A. Naylor J. Chem. SOC.(B), 1971, 1967. H. J. Brass, J. 0. Edwards, and N. J. Fina, J. C. S. Perkin ZZ, 1972, 726.

135

Quinquevalent Phosphorus Acids

The rate of hydrolysis of isopropyl methylphosphonofluoridate (sarin) in sea water has been measured.sa In solvents of low polarity the rate of solvolysis of phosphinyl and phosphonyl halides is catalysed by hydrogen ~hloride,~'the catalytic effect decreasing along the series as shown : Et,POCI

>

EtO-P-Cl /\ Me 0

>

EtS-P-CI /\ Me 0

>

(MeO),POCI

>

POC13

An SNl (P) mechanism appears to operate in the aqueous solvolysis of di-t-butylphosphinic chloride,88whereas studies on the hydrolysis of the phosphinylguanidine derivative (9 1) in sulphuric acid are consistent with an A2 mechanism (in spite of somewhat unusual solvent isotope effect).

At high acid concentrations the mechanism appears to change and may involve diprotonation of the guanidine moiety.89 Relative rates of alkaline solvolysis of a series of S-esters of methylphosphonothioic acid (92) have been measured and a comparison made between the rates of hydrolysis of bischloromethylphosphinic acid (93) and SEt MePl 11 R 0 (92)

(C I C H, 1 P c

X

Y-Et (93) X , Y = 0 or S

0

II

Ph- P-OCHPh I I H Me (94)

diethylphosphinic acid esters, also under alkaline condition^.^^ Although the neutral solvolysis of (94) seems to proceed with alkyl-oxygen fission, the base-catalysed reaction (at pH 7.0) probably involves tautomerism to the p h ~ s p h i t e . ~ ~

=-

86

87

88 89 90

91 92

J. Epstein, Science, 1970, 170, 1396. A. A. Nemysheva, M. V. Ermolaeva, and I. L. Khunyants, Zhur. obshchei Khim., 1970, 40, 2022. P. Haake and P. S. Ossip, J. Amer. Chem. SOC.,1971, 93, 6919. G . Capozzi and P. Haake, J . Amer. Chem. Soc., 1972,94, 3249. V. E. Belskii, N. N. Bezzubova, V. N . Elisenkov, and A. N. Pudovik, Zhur. obshchei Khim., 1970, 40, 2357. V. E. Belskii, N. N. Bezzubova, V. N. Elisenkov, N. I. Rizpolozhenskii, and A. N. Pudovik, Doklady Akad. Nauk S.S.S.R., 1971, 197, 85 (Chem. Abs., 1971, 75,87 764). D. S. Noyce and J. A. Virgilio, J. Org. Chem., 1972, 37, 1052.

136

Organophosphorus Chemistry

It has been shown that the rearrangement of a-hydroxyalkylphosphonic acid diesters to phosphates is subject to general base catalysis and a transition state similar to (95) was Hydrolysis of the aroylphosphonate esters (96) in aqueous dioxan with phosphate buffer is also 0 RO, 11 .O- H ..-B P” I RO’ ‘C(CF,),

(95)

subject to general base catalysis with a p value consistent with attack on the carbonyl group.94 This last observation is in accord with independent observations that nucleophiles attack (96) at the carbonyl group leading, in the case of hydroxylamine, to the formation of benzonitriles (Scheme 0

-

ArCO PO(OR),

NH,OH

II

+

> Arc-P(OR),

II N-OH Scheme 10

(96)

---+

ArCN

+

(RO),PO,H

Solvolysis of the a-haloalkylphosphinic esters (97) and (98) with methoxide ion in methanol leads to the rearranged phosphonate esters (99) and The formation of these products can be readily accommodated in terms of a cyclic phosphinate intermediate. Stereochemical consequences of nucleophilic attack on phosphinate and phosphonate esters continue to attract attention and have produced some unexpected observations. Thus whereas the reaction of methoxide ion 0 II MeCHCl-P-CH,CO,Me I OMe

MeO-

--+

MewCO,Me O -\M !/e Me0 0

MeO,C- CH,.CHMe-PO(OMe), (99) 0 II PhCHBr - P-CHBrPh I

OMe

MeO-

---+

PhCH=C,

, PO(OMe), Ph

(98) s3 O4

86 O8

A. F. Janzen and T. G. Smyrl, Canad. J. Chem., 1972, 50, 1205. W. Jugelt, S. Andreae, and G. Schubert, J. prakt. Chem., 1971, 313, 83. I. Shahak and J. Peretz, Israel J. Chem., 1971, 9, 3 5 . P. Burns, G. Capozzi, and P. Haake, Tetrahedron Letters, 1972, 925.

137

Quinquevalent Phosphorus Acids

with (101) has been proved conclusively to involve loss of thiolate ion and inversion of configurati~n,~~ the corresponding reaction of (102) with SMe I

O=P-.

j 'OR

Ph

SMe O=P-Me \ OPri

phenyl Grignard (also proceeding with loss of mercaptide) gives retention of configuration g8-a result which necessitates revision of several previously accepted configurational assignments. There is at present no adequate theory to account for these observations on mixed OS-esters, but some useful generalizations have been proposed to account for the stereochemical consequences of nucleophilic substitution in phosphetan derivative^.^^ Reactions of Phosphonic and Phosphinic Acid Derivatives.-Diphenylphosphinic peroxide (103) has been shown to undergo a remarkable rearrangement, either thermally or on irradiation, to give the mixed phosphinic phosphonic anhydride (1O4).lo0 Using (103) labelled with ISO

o* o*

4 PhzP,

0-0

\:PPh,

A CH,C,,~

Ph Ph2P-O-P/ II II'OPh o* 0"

in both phosphoryl oxygens it was found that whereas the thermal reaction resulted in rearranged product labelled exclusively in the phosphoryl oxygens, the photo-reaction gave scrambling. This implies that thermal reaction proceeded either by a concerted process or by a very intimate ion pair in which the two oxygens in the anion fragment remain distinguishable. The stereochemistry of the reaction of phosphinate esters with organometallic derivatives has been reviewed.lol Oxidation of the phosphinothioate ester (105) to the P=O analogue with rn-chloroperoxybenzoicacid has been shown to proceed with > 90% retention of configuration, whereas under the

97

88

99

100 101

W. B. Farnham, K. Mislow, N. Mandel, and J. Donohue, J. C. S. Chem. Comm., 1972, 120. J. Donohue, N. Mandell, W. B. Farnham, R. K. Murray, K. Mislow, and H. P. Benschop, J. Amer. Chem. SOC.,1971, 93, 3792. J. R. Corfield, R. K. Oram, D. J. H. Smith, and S. Trippett J. C. S. Perkin ZZ, 1972,713. R. L. Dannley, R. L. Waller, R. V. Hoffmann, and R. F. Hudson, J . Org. Chem., 1972, 37, 418. K. Mislow and G . Zon, Fortschr. Chem. Forsch., 1971, 19, 61.

0rganophosphor us Chemistry

138

more acidic condition of peroxytrifluoroaceticacid inversionpredominates.lo2 This therefore is reasonably consistent with earlier results using dinitrogen tetroxide and nitric acid. Esters of p-carboxyphosphonic acids (106) are broken down by base via P-C rather than C-C cleavage,lo3which doubtless reflects a combination of the greater stability of the latter bond coupled with more efficient stabilization of the expelled carbanion by the C=O relative to the P=O group. The cyclic anhydride (107) is opened by thiols by attack at 0

11 f ,

(EtO),P -CHCO,Et

"o,40 R:IS]{

R'

I<

( 107)

* , I

0

II

R'--P-CH2-CHCOSR3 I I OH R2 (major)

+

0 It R'--P-CH2-CHC0,H I I S R3 R2 (minor)

ArSO,CH, PO(OEt), (108)

both the carbonyl and the phosphoryl group,lo4the former predominating to give a product which readily eliminated a thiol to form a dimeric anhydride. Nucleophilic attack on the ester (log), however, occurs at carbon.lo5 The a-diazoalkylphosphonic esters may be converted into their silver or mercury derivatives by treatment with the appropriate metal oxide.lo6 Thermal addition of (109) to norbornene gives the pyrazoline derivatives (1 lo), which are converted on irradiation into the cyclopropyl derivatives (lll).lo7 It was shown that the product of direct irradiation retained the stereochemistry, whereas the photosensitized reaction was not stereospecific. Studies have been reported on the attack of electrophiles on the P=O and P=N- systems. It was found that there was a good correlation between the reactivity of a series of phosphonates and phosphinates and derivatives (1 12) towards triethyloxonium fluoroborate and the chemical shift of the methyl protons.lo8 Similarly, the reactivity of a similar series 102

103 104

105

106 107

108

A. W. Herriott, J. Amer. Chem. SOC.,1971, 93, 3304. Y. Okamoto and H. Sakurai, Kogyo Kagaku Zusshi, 1970,73,2664 (Chem. Abs., 1971, 74, 125798). M. A. Vasyanima, V. K. Khairullin, and A. N. Pudovik, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 1722 (Chem. Abs., 1971,75, 151 872). R. V. Vizgert and M. P. Volashin, Zhur. obshchei Khim., 1971, 41, 429. M. Regitz, A. Liedhegener, U. Eckstein, M. Martin, and W. Auschutz, Annalen, 1971, 748, 207. H. J. Callot and C. Benezra, Canad. J. Chem., 1972, 50, 1078. L. V. Nesterov, A. Y. Kessel, Y. Y. Samitov, and A. A. Musina, Zhur. obshchei Khim., 1970, 40, 1237.

139

Quinquevalent Phosphor us A cids

x\,P=NR

yz/

of phosphonimides (1 13) towards hydrolysis to the P=O analogues by acid was consistent with the predicted effect of the substituents on the basicity.lo9 The coupling constant J p N C H has been used to determine the position of protonation in a series of NN-dimethylphosphinamides.l1° Chlorine converts the phosphinimide derivative (1 14) into the N-chloro-compound (1 15).ll1 p-Aminoethylphosphonic acid (1 16a), as expected, readily undergoes elimination to ethylene with nitrous acid, but the phosphine oxide analogue (1 16b), which cannot eliminate a metaphosphate intermediate, gives the alcohol under these conditions (Scheme 1 1).l12 Further studies on the ester (1 17) have established that the oximino-group undergoes syn-anti 0 R, II ,P-CCH2CH,NkI, R (a) R = HO (b) R = Ph

I

tINO,

(R = Ho)+

H,PO,

+

CH,=CH,

HNO,

0

(R = Ph)

II Ph P C H2CH ?OH

log

111

112

Scheme 11

M. I. Kabachnik, Phosphorus, 1971, 1, 117, K. E. De Bruin, A. G . Padilla, and D. M. Johnson, Tetrahedron Letters, 1971, 4279. E. S. Kosrov and C. T. Gautzdamaka, Zhur. obshchei Khim., 1972,42, 106. P. Mastalerz and G. Richtaski, Roczniki Chem., 1971, 45, 763.

140

Organophosphorus Chemistry 0

PhC-CH20- P-0 II I NOH Me

isomerization in acidic conditions and thus it seems probable that the unexpectedly rapid solvolysis of the anti-isomer is due to this cause.l13 The aminoacetal derivative (1 18) is converted into the iminium salt (1 19) on treatment with thionyl ch10ride.l~~Acetyl chloride reacts with phosphorous acid to give a compound whose lH n.m.r. is consistent only with structures (120) or (121).l15 0 II ,OMe (RO) P -C H NMe,

,

SOCI,

40 CI (RO)ZP, + CH=NMe,

Phosphinodithioic acids react with stannic chloride at - 25" C to substitute one of the chlorine atoms,lls but the related phosphonochloridothioate gives (1 22) with the same reagent.l17 The bis(phosphin0dithioic) acid (123) forms polymeric complexes with transition-metal ions

S II R - P -(CH,), I

SH

S II - P -R I

SH

123) P. Blumbergs, C . B. Thanwalla, A. B. Ash, C. N. Lieske, and G . M. Steinberg, J. Org. Chem., 1971,36,2623. 114 H. Gross and B. Costisella, Annalen, 1971, 750, 41. 115 G. Brun and C . Blanchard, Compt. rend., 1971, 272, C , 2156. 118 A. A. Muramova, I. Y. Kuramshin, and E. G. Yarkova, Zhur. obshchei Khim., 1971, 41, 1967. n7 A. N. Pudovik, A. A. Muramova, I. Y . Kuramshin, and E. G. Yarkova, Zhur. obshchei Khim., 1972, 42, 317.

113

Quinquevalent Phosphorus Acids 141 (Co2+, Ni2+, or Pd2+) which can form adducts with amines, a property which may make them useful for chromatographic separations.l18

3 Miscellaneous Conformational problems in five- and six-membered rings containing phosphorus continue to attract a t t e n t i ~ n . l l ~ -Care l ~ ~ must be taken in the use of n.m.r. shift reagents to assist in the elucidation of conformational problems since it has been found that for (124), which has a relatively

small free-energy difference between the two possible chair forms, co-ordination to Eu3+is sufficient to change the conformation.123 Diesters of acetaldehydephosphonic acid (125) exist exclusively in the keto-form in carbon tetrachloride solution, whereas in the presence of triethylamine, which can hydrogen-bond, the enol form ~red0rninates.l~~ Similarly, spectral evidence has been presented to demonstrate the existence of tautomerism in the metal derivatives of the cyanomethylphosphonic esters (126).125 OHC.CH2PO(ORJ2 (1 25)

HOCH=CHPO(OR),

NCCH, PO(OR), ( 126)

The binaphthyl phosphate ester (127) has been proposed as a resolving agent and its absolute configuration determined.12s A successful resolution procedure for the 0-methyl ester of t-butylphosphonothioic acid has been rep0~ted.l~'N.m.r. will distinguish between the diastereoisomers of (128) 12* and between the diastereoisomeric salts of (129) with a-phenylethylamine.129 W. Kuchen, J. Deventhal, and K. Heck, Angew. Chem. Znternat. Edn., 1972, 11,435. K. Bergesen and T. Vikane, Acfa. Chem. Scand., 1971, 25, 1147. l Z oJ. P. Majoral and J. Navech, Bull. SOC.chim. France, 1971, 1331, 2609. lZ1 R. Kraemer and J. Navech, Bull. SOC.chim. France, 1971, 3580. l Z 2 D. W. White, G. K. McEwen, R. D. Bertrand, and J. G. Verkade, J. Chem. SOC.(B), 1971, 1454. l Z 3 W. G . Bentrude, H. Tan, and K. C. Yee, J. Amer. Chem. SOC.,1972,94, 3264. l Z 4 A. I. Razumov, G . A. Savicheva, T. V. Zykova, M. P. Sokolov, B. G . Liober, and R. A. Salakhutdinov, Zhur. obshchei Khirn., 1971, 41, 1954. 125 M. Kirilov and G. Petrov, Chem. Ber., 1971, 104, 3073. lZ6 J. Jacques, C. Fouquey, and R. Viterbo, Tetrahedron Letters, 1971, 4617. lZ7B. Krawiecka and J. Michalski, Bull. Acad. polon. Sci., S&. Sci. chim., 1971, 19, 377 (Chem. Abs., 1971,75, 140 944). lZ8 T. A. Mastryukova, A. E. Shipov, M. S. Vaisberg, P. V. Petrovskii,and M. I. Kabachnik, Zzvest, Acad. Nauk S.S.S.R., Ser. khim., 1971, 1841 (Chem. Abs., 1971, 75, 1841). l t 9 M. Mikolajczyk and J. Omelanczuk, Tetrahedron Letters, 1972, 1539. llS

Organophosphorus Chemistry

142

S

II

MeO-P-SCH,CONHCHCO,H I I R OEt ( 128)

The dissociation constants of a- and /3-naphthyl phosphate have been determined.130 Basicity measurements on a series of substituted phosphorimide derivatives (130) have shown that there is generally good agreement between the observed values and those predicted from Kabachnik

x\

Y-P=NAr Z' X, Y, Z = alkyl, aryl, alkoxy, or dialkylamino ( 1 30)

substitution pararneters.l3l The enthalpies of formation of complexes of boron trifluoride with a series of 2-0xo-l,3,2-dioxaphosphorinans have also been ~ e p 0 r t e d . l ~ ~ The complexes of (131) with metals have been investigated by U.V. spectral Unlike its carboxylic analogue, the triphosphonic acid (132) appears to be a poor chelating agent.134

130

lal

Isa 133 134

0. Makitie and S. Mirttinen, Acta Chem. Scand., 1971, 25, 1146. G . K. Genkina, B. A. Korolev, and S. S. Titov, Zhztr. obshchei Khim.,1971, 41, 80. P. C. Maria, L. Elegant, M. Azzaro, J. P. Marjoral, and J. Navech, Bull Soc. chim. France, 1971, 3750. P. Christophliemk, V. V. K. Rao, I. Tossidis, and A. Muller, Chem. Ber., 1972, 105, 1736. L. Maier, Phosphorus, 1971, 1, 67.

7

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

1 Introduction The number of papers published during the past year on biochemically interesting organophosphorus compounds has increased considerably, necessitating some selection on the part of the reporter to keep this chapter to a reasonable length. One of the most interesting features of recently published work has been the increased application of affinity chromatography and insolubilized enzymes to biochemical problems. Cyclic AMP* has continued to justify investigation of its properties and mode of a ~ t i o n and , ~ the organic chemistry of nucleic acids up to 1969 has been summarized by Russian worker^.^ 2 Mono-, Oligo-, and Poly-nucleotides

Mononucleotides.-New mononucleotides have recently been prepared by the phosphorylation of nucleosides by conventional methods [ (1),5 (2),8 (3),’ and (4)*] and by the modification of the base (5)a and (6)1° or sugar (7) l1 residues of nucleotides. The use of phosphorus oxychloride in solution in trimethyl phosphate is a well-established method for the

’ lo l1

P.Cuatrecasas and C. B. Anfinsen, Ann. Rev. Biochem., 1971, 40, 259. H. D. Orth and W. Briimmer, Angew. Chem. Internat. Edn., 1972,11,249; K. Katchalski, I. Silman, and R. Goldman, Ado. Enzymol., 1971, 34,445. G . A. Robison, R. W. Butcher, and E. W. Sutherland, ‘Cyclic AMP’, Academic Press, London, 1971. N. K. Kochetkov and E. I. Budovskii, ‘Organic Chemistry of Nucleic Acids’, Plenum Press, London, 1972. P. F. Torrence and B. Witkop, Biochemistry, 1972, 11, 1737. R. Thedford and D. B. Straus, Biochem. Biophys. Res. Comm., 1972,47, 1237. A. Holf, R. W. Bald, and F. Sorm, Coll. Czech. Chem. Comm., 1972, 37, 592. A. Holy and F. Sorm, Coll. Czech. Chem. Comm,, 1971, 36, 3282. H. J. Brentnall and D. W. Hutchinson, Tetrahedron Letters, 1972, 2595. K. Mureyama, B. J. Bauer, D. A. Schuman, R. K. Robins, and L. H. Simon, Biochemistry, 1971, 10, 2390. K. Geider, European J. Biochem., 1972, 27, 554.

*Abbreviations used in this chapter for biochemical compounds may be found in the Instructions to Authors of the Biochemical Journal.

143

144

Organophosphorus Chemistry

(p~ jN/I A

HN%

oAN

N I R

I

R

= P-D-ri bofuraiiosyl

YYoH HO

OH

(4)

O=P-0 I HO

(3)

(2)

(1)

R

I

R

OH

\

H d

OH

(5)

H‘

H (7)

( 6)

phosphorylation of 2’,3’-O-isopropylidene nucleosides,12ultimately leading to the 5’-nucleotides. However, the direct phosphorylation of unprotected nucleosides by phosphorus oxychloride in aqueous solution in the presence of calcium or strontium hydroxide gives predominately the nucleoside l2

M. Yoshikawa, T. Kato, and T. Takanisji, Tetrahedron Letters, 1967, 5065; K. H. Scheit and P. Faerber, European J. Biochem., 1971, 24, 385; B. Janik, M. P. Kotick, T. H. Kreiser, L. F. Reverman, R. G. Sommer, and D. P. Wilson, Biochem. Biophys. Res. Comm.,1972, 46, 1153; J. Hobbs, H. Sternbach, and F. Eckstein, ibid., p. 1509.

145 2’(3’)-monophosphates.13 Details of the use of o-phenylene phosphorochloridate (8; X = Cl),14 o-phenylene phosphate (8; X = OH),14 or p-nitrophenyl phosphate l6 for the phosphorylation of nucleosides have appeared. In the latter case, the formation of an N-phosphopyridinium intermediate is postulated; similar intermediates are believed to be involved in the catalysis by 2-picoline of the reaction between phosphorus oxychloride and amines.16 The deamination of phosphoramidates by isoamyl nitrite has been mentioned in previous Reports and is the basis of a method for the protection of 5’-phosphoryl groups in the synthesis of oligonucleotide^.^^ The oxidation of nucleoside phosphoramidates with bromine in the presence of alcohols leads to phosphodiesters.l* The N-bromophosphoramidate which is presumably an intermediate should break down by a pathway which is similar to that of the acid-catalysed decomposition of phosphoramidates. A new method for the preparation of 5’-amino-5’-deoxynucleotideshas been described,lg based on the reaction between phosphorus triesters and phenyl azide.20 Treatment of protected 5’-azido-5’-deoxynucleosideswith trimethyl or triphenyl phosphite leads, after removal of the nucleoside protecting groups and one of the esterifying groups from the phosphoryl residue, to the phosphoramidates (9). Snake venom phosphodiesterase hydrolyses (9) to 5’-aminonucleosides.

Phosphates and Phosphonates of Biochemical Interest

PhN,

+

(RO),P w N2

+

(RO),P=NPh

H,O

(RO),PNHPh II

0

II

RIOPNHR~

I

OH (9)

R’ = Ph Or Me R2 = nucleoside-5’

Condensation of N-benzyloxycarbonylaminomethanephosphoric acid with 2’,3’-O-isopropylidene nucleosides in the presence of an aryl sulphonyl chloride gives the corresponding phosphonates, which on treatment with Although aqueous hydrobromic acid lead to the nucleotide analogues ( (10) are resistant to alkaline phosphatase, they are degraded slowly by snake venom 5’-nucleotidase. Uridine 5’-phosphofluoridate is also degraded slowly by the latter enzyme whereas it is resistant to the former.22 la lo

l5 l6

l7

lo 2o

21

aa

Y. Sanno, Y. Kanai, A. Nohara, H. Honda, and Y. Miyata, Takeda Kenkyusho Ho, 1971, 30, 217 (Chem. Abs., 1971,75, 118 522). T. A. Khwaja and C. B. Reese, Tetrahedron, 1971, 27, 6189. T. Hata and K. J. Chong, Bull. Chem. Soc. Japan, 1972, 45, 654. E. Jampel, M. Wakselman, and M. Vilkas, Tetrahedron Letters, 1968, 3533. E. Ohtsuka, M Ubasawa, and M. Ikehara, J. Amer. Chem. Soc., 1970, 92, 5507. E. Ohtsuka, S. Morioka, and M. Ikehara, Tetrahedron Letters, 1972, 2553. W. Freist, K. Schattka, F. Cramer, and B. Jastorff, Chem. Ber., 1972, 105,991. M. I. Kabachnik and V. A. Gilyarov, Izvest. Akad. Nauk S.S.S.R., Otdel. khim. Nauk, 1956, 790 (Chem. Abs., 1957, 51, 1823). N. N. Gulyaev and A. Holy, F.E.B.S. Letters, 1972, 22, 294. Z. Kuderovh and J. Skoda, Biochim. Biophys. Acta, 1971, 247, 194.

146

Organophosphorus Chemistry 0

B

II HO-PO H O-!OVo\/

d

H N H

w

z

y

H2NcHz

HO

o

y

B

OH

Cyanamide, which can tautomerize to carbodi-imide (1 l), is formed by irradiation of ammonium cyanide solutions or by electron irradiation of a mixture of methane, ammonia, and water, conditions which may

U.V.

NH,CN

9 NH=C=NH ( 1 1)

simulate a prebiotic environment. When thymidine 5’-phosphate is heated with cyanamide in neutral aqueous solution, oligomers containing up to four base residues are If a clay, e.g. montmorillonite, is added to the reaction mixture, pentamers are produced, which suggests that inorganic surfaces cause chain elongation and hence could have played an important part in prebiotic syntheses. Deoxyribonucleoside 5’-phosphates polymerize when heated in D M F at reflux t e m p e r a t u ~ e .This ~ ~ process is catalysed by protons or proton donors such as ~-imidazolyl-4(5)-propanoicacid (1 2) or trialkylammonium hydrochlorides. About 90% of the oligonucleotides contain (3’-5’) linkages and 10%at least one (5’-5’) link; no oligomers containing (3’-3’) links could be detected as all of the oligomeric products were degraded by snake venom phosphodiesterase. The oligomerization appears to be reversible in DMF

but if pyridine is used as solvent only the breakdown of oligomers is observed and no polymerization can be detected. It seems likely that in DMF in the presence of protons, a phosphorylating species is formed, possibly an imidoyl phosphate (1 3). This will give rise to P1P2-dinucleoside pyrophosphates which are known to produce oligomers when heated in DMF. It is claimed that this reacion could occur in a prebiotic environment. Polybasic amines, e.g. ethylene diamine and spermidine, stabilize the triple helix formed by adenosine 2’,3’-cyclic phosphate with poly rU, 23 24

J. D. Ibanez, A, P. Kimball, and J. Orb, Science, 1971, 173, 444. 0. Pongs and P. 0. P. Ts’o, J. Arner. Chem. SOC., 1971, 93, 5241.

Phosphates and Phosphonates of Biochemical Interest

147

and these amines will also catalyse the formation of ApA from the cyclic phosphate.25 Although predominately (2'- 5')-internucleotide bonds are formed, it is suggested that this process may have been important in prebiotic conditions. The methyl and ethyl phosphotriesters of both d(TpT) and d(ApA) have been prepared as diastereoisomeric pairs (14) and (1 5), which could not be separated but which could be observed by lH n.m.r. spectroscopy.26 The

,

,

O

W

B

""WB

esterified dinucleoside phosphates form complexes with poly A which are more stable than those formed from the corresponding unesterified dinucleoside phosphates. The esterified compounds are resistant to hydrolysis by nucleases. Cyclic AMP (CAMP) has continued to attract considerable attention during the past year. 5'-Amino-5'-deoxy-derivatives (1 6) 27 and the ara.analogue (17)28 of cAMP have been prepared but their biochemical

HN\wA O=P-O I

OH

properties have not been investigated. It has been observed for a series of 8-substituted cAMP derivatives (6) lo that all except 8-thio-CAMP were appreciably more active than cAMP in stimulating glycolysis in a wholecell system.2BThis increased activity has been attributed to better penetration into the cells by the 8-substituted analogues. 25 26

2' 28

2a

M. Renz, R. Lohrmann, and L. E. Orgel, Biochim. Biophys. Acta, 1971, 240,463. P. S. Miller, K. N. Fang, N. S. Kondo, and P. 0. P. Ts'o, J . Amer. Chem. SOC.,1971. 93, 6657. A. Murayama, B. Jastorff, F. Cramer, and H. Hettler, J. Org. Chem., 1971, 36, 3029. W. W. Lee, L. V. Fischer, and L. Goodman, J . Heterocyclic Chem., 1971, 8, 179.

R. J. Bauer, K. R. Swiatek, R. K. Robins, and L. N. Simon, Biochem. Biophys. Res. Comm., 1971,45, 526.

148

Organophosphorus Chemistry

Under normal conditions, enzyme substrates which bear ‘photoaffinity labels’ react in the expected manner; however, on photolysis they are converted into highly reactive intermediates which can form covalent bonds with amino-acid residues near the active site of the enzyme. O-2’-Diazonialonyl-cAMP (18) is an example of a photoaffinity-labelled

substrate as it is converted on irradiation into a carbene which is incorporated into the CAMP-binding site of rabbit-muscle phosphofructokinase.30 N(6)-Diazomalonyl analogues did not bind to the enzyme under comparable conditions. N(6)-~-Aminocaproyl-cAMPwill react with Sepharose which has been treated with cyanogen bromide to give insolubilized CAMP,^^ which has been used to purify protein kinase. After purification, the kinase does not require cAMP for activation and will not bind CAMP. It is postulated that a subunit which binds cAMP has been removed from the kinase during chromatography and is retained on the insolubilized CAMP. An alternative method 32 for the insolubilization of cAMP is through the 8-position of the purine [6; X = SCH,CH,NHCO(CH,),NH,] a ‘spacer’ being used to hold the cAMP away from the Sepharose surface. It has been shown that in a medium of pH > 5 this sample of bound cAMP releases small amounts of material which contains CAMP, which means that investigations on insoluble hormone activators of this type must be treated with caution as the traces of soluble cAMP could materially effect the results. N(6)-(6-Aminohexyl)-AMP has also been bound to cyanogen bromidetreated Sepharose and has been used to isolate lactate dehydrogenase and glyceraldehyde 3-phosphate dehydr~genase.~~ 6-(Purine-5’-ribonucleotide)-5-(2-nitrobenzoicacid) thioether (19) is an analogue of AMP and has been used as an affinity label in the activation on phosphorylase b from rabbit muscle.34 2-Nitro-4-mercaptobenzoic acid is liberated in this reaction and there is a stoicheiometric relationship between the activation and the amount of nucleotide incorporated into the enzyme. The nucleotide is covalently linked to the protein, presumably near the active site of the enzyme. 30 31 32

33 34

D. J. Brunswick and B. S. Cooperman, Proc. Nat. Acad. Sci. U.S.A., 1971, 68, 1801. M. Wilchek, Y. Salomon, M. Lowe, and Z. Selinger, Biochem. Biophys. Res. Comm., 1971, 45, 1177. G. I. Tesser, H. U. Fisch, and R. Schwyzer, F.E.B.S. Letters, 1972, 23, 56. K. Mosbach, H. Guilford, R. Ohlsson, and M. Scott, Biochem. J., 1972, 127, 625. F. W. Hulla and H. Fasold, Biochemistry, 1972, 11, 1056.

Phosphates and Phosphonates of Biochemical Interest

149

The hydrolysis of a series of 5- and 6-substituted pyrimidine ribonucleoside 2’,3’-cyclic phosphates by pancreatic RNase and T2RNase has been In general, substitution in the 5-position has little effect on the rate of hydrolysis of a cyclic phosphate by either enzyme. However, substitution in the 6-position has an inhibitory effect on hydrolysis by pancreatic RNase and methylation at N(3) has a pronounced inhibitory effect on the hydrolysis by either enzyme. 3-@-~-Ribofuranosyl)uracil 2’,3’-cyclic phosphate is also a poor substrate for these enzymes.38 The sequential removal of single residues from the 3’-hydroxyl end of polyribonucleotides by treatment with first periodate and then a primary amine is an important method for the structure determination of these polymers. A detailed study of this reaction using AMP as substrate has now been p~blished.~’ Products of this reaction which have been isolated are adenine, carbon dioxide, formic acid, and inorganic phosphate. The release of phosphate requires one equivalent each of periodate and the primary amine whereas three additional equivalents of periodate are required before adenine is released. The rate of phosphate release is too great to be accounted for by the formation of an aldimine but is explained (Scheme 1) by the participation of a cyclic enamine (20). After elimination of phosphate from (20), stepwiseoxidation by three equivalents of periodate gives the observed reaction products. The amine-induced cleavage of 3’-phosphodiester bonds in polyribonucleotides (Scheme 2) will only take place if there is a free glycosidic centre /Ito the phosphoryl g r o ~ p . ~Such * a relationship is found in apurinic and apyrimidinic acids, which are known to be degraded by amines. Incubation of UMP with acid phosphatase in an 80% (v/v) solution of ethanol results in the rapid decomposition of substrate and the production of uridine and ethyl p h ~ s p h a t e .Whereas ~~ the latter is the major product 35

36 37

38

39

A. Holy and R. Bald, COIL Czech. Chem. Comm., 1971, 36, 2809. R. W. Bald and A. Holy, CON.Czech. Chem. Comm., 1971, 36, 3657. D. H. Rammler, Biochemistry, 1971, 10, 4699. M. F. Tmchinsky, L. I. Guskova, I. Hazai, E. I. Budowsky, and N. K. Kochetkov, Biochim, Biophys. Acta, 1971, 254, 366. M. Tomaszewski and J. Buchowicz, Biochem. J., 1971, 124, 189.

6

150

Organophosphorus Chemistry

Me Scheme 1

at ethanol concentrations above 15% (v/v), below this concentration orthophosphate is the only product. One of the primary steps in the biosynthesis of proteins is the transfer of aminoacyl residues from an aminoacyl adenylate to tRNA. It has recently

O=P-OH

I

I

! Scheme 2

151

Phosphates and Phosphonates of Biochemical Interest

been shown that N-acetylglycyl adenylate (2 l), like acetyl a d e n ~ l a t ewill ,~~ react with imidazole to give N-acetylglycylimidazolewhich will transfer the aminoacyl moiety to the sugar residues of monon~cleotides.~~ 0 II

A-0-

0 II

P-O-C-CH,NHAc I

OH

(21)

The nucleophilic reactions of deoxyribonucleoside phosphorothioates have been studied 42 and deoxyribonucleotide oligomers have been chemically synthesized43 using an S-ethyl group for protection of the 5’-phosphoryl group of the nucleotide. The synthesis involved the sequential addition of oligomeric units to the growing nucleotide chain which contained the S-ethyl group. The latter was finally removed by oxidation with aqueous iodine. Nucleoside Po1yphosphates.-Adenylyl 44 and guanylyl 45 imidodiphosphates [AMPPNP and GMPPNP (22) 3 have been prepared and their 0 0 11 H 11

HO-P -N-P-0-P OH I OH I

0 II

yoyB

-0 bH

HO AMPPNP B GMPPNP B

= =

OH

Ad G

(22)

reactions with hydrolytic enzymes studied. Snake venom phosphodiesterase cleaves both AMPPNP and GMPPNP with release of imidodiphosphate. However, there appears to be a difference in the behaviour of the two compounds with alkaline phosphatases. Calf intestinal alkaline phosphatase degrades GMPPNP to the n u ~ l e o s i d e whereas ,~~ the phosphatase derived from E. coli degrades AMPPNP to adenine 5’-diphosphoramidate (ADPNH2).44This may be due to a difference in purity of the two enzymes. Analogues of nucleoside di- and tri-phosphates bearing a sulphur atom attached to the terminal phosphorus atom are degraded slowly by the 40

I1 4a

43

44 45

W. P. Jencks, Biochim. Biophys. Acta, 1957, 24, 227; W. P. Jencks and J. Carriuolo, J . Biol. Chem., 1959, 234, 1272. J. C. Lacey, jun., and W. E. White, jun., Biochem. Biophys. Res. Comm., 1972, 47, 565. S. Chladek and J. Nagyvary, J. Amer. Chem. SOC.,1972, 94,2079. A. F. Cook, E. P. Heimer, M. J. Holman, D. T. Maichuk, and A. L. Nussbaum, J. Amer. Chem. SOC.,1972, 94, 1334; E. Heimer, M. Ahmad, S. Roy, A. Ramel, and A. L. Nussbaum, ibid., p. 1707. R. G. Yount, D. Babcock, W. Ballantyne, and D. Ojala, Biochemistry, 1971, 10, 2484. F. Eckstein, M. Kettler, and A. Parmeggiani, Biochem. Biophys. Res. Comm., 1971,45, 1151.

152

Organophosphorus Chemistry

intestinal alkaline phosphatase, presumably to the n u ~ l e o s i d e .Myokinase ~~ and hexokinase will not catalyse the transfer of the terminal phosphoryl residue from AMPPNP 44 and neither myosin nor heavy meromyosin will cleave the terminal bond.47 Like the corresponding methylene derivative (GMPPCH,P), GMPPNP is a competitive inhibitor of ribosome-dependent GTPase from E. coli. Interest in guanylyl 3’,5’-dipyrophosphate [PpGpp (23)] has continued. This nucleotide is implicated in RNA synthesis in E. coli, 48 and ppGpp

/

E-1306P20

‘OH

(23)

levels increase sharply when the bacteria are starved of amino-acids or glucose.4g Early reports 50 that rifampicin, an antibiotic which inhibits RNA chain initiation in bacteria, inhibits the formation of ppGpp have been shown to be incorrect.sl An analogue of ATP (24) in which a stable nitroxide free radical is attached through a sulphur atom to the 6-position of the purine ring will NHCOCH2- S M Me e&.

Me

-Q NvN-R

I

‘0

(24)

bind to both actin and creatine kinase.62 The signals in the e.s.r. spectrum of the actin-bound radical are broad, but with time sharp signals appear in the spectrum, indicating that the nucleotide is released. Conformationally restricted analogues of ribonucleoside triphosphates (e.g. 8-bromo- or 8-keto-guanosine triphosphates) are strong inhibitors of E. coli RNA polymerase while 6-methylcytidine triphosphate is not polymerized at all by the enzyme.53 8-Bromo- and 8-amino-ATP react with hexokinase and glycerokinaseY6* indicating that the conformation of the substrate cannot be important for these enzymes. 46

47 48

48

B1

63

53 64

R. S. Goody and F. Eckstein, J. Amer. Chem. SOC.,1971, 93, 6252. R. G. Yount, D . Ojala, and D. Babcock, Biochemistry, 1971, 10,2490. M. Cashel and B. Kalbacher, J. Biol. Chem., 1970, 245, 2309; R. B. Harshman and H. Yamazaki, Biochemistry, 1971, 10, 3980. G. Edlin and P. Donini, J. Biol. Chem., 1971, 246, 4371. J. T. Wong and R. N. Nazar, J. Biol. Chem., 1970,245,4591. H. Erlich, T. Laffler, and J. Gallant, J. Biol. Chem., 1971, 246, 6002. R. Cooke and J. Duke, J . Biol. Chem., 1971, 246, 6360. A. M. Kapuler and E. Reich, Biochemistry, 1971, 10, 4050. A. Gabbai and T. Posternak, Helv.Chim. Acta, 1971, 54, 2141.

Phosphates and Phosphonates of Biochemical Interest

153

Standard-free-energy maps for the hydrolysis of ATP as a function of pH and bivalent cation concentration have been published.55 Quantum mechanical calculations s6 show that ATP should have a tendency to adopt a folded conformation, in agreement with crystallographic data.57 Oligo- and Poly-nuc1eotides.-Current approaches to the chemical synthesis of oligodeoxyribonucleotideshave been reviewed.58 One solution to the problem of chemical synthesis is to build up an oligonucleotide on an insoluble support and hence avoid difficulties in separation and purification of intermediates. Previous work on this topic has been mentioned in earlier Reports. Polystyrene and cross-linked styrene-divinylbenzene copolymers bearing p-methoxytrityl chloride groups have been used 59-61 to attach the support to the first monomer through its 5’-hydroxy-group. Additional protected nucleosides are then added in a stepwise fashion, the internucleotide bond being achieved by conventional means using a carbodiimide or an arylsulphonyl chloride. The polynucleotide is cleaved from the support at the end of the reaction sequence with acid. In another method, deoxyribonucleosides which have been linked through their 5’-hydroxy-groups to a chloromethylated styrenedivinylbenzene copolymer are phosphitylated using phosphorous trichloride.s2 The 3’-monophosphites are then joined to another nucleoside by treatment with mercuric chloride in pyridine. It is claimed that unprotected nucleosides can be used in this synthetic scheme. Succinylated polystyrene (25) is another support which has been attached to the 5’-hydroxy-group of ribonucleosides and oligonucleotides built up in the conventional manner,s3 the oligomer being

released from the polymer by the action of alkali. Ribonucleotides can be bound to 4‘-aminophenoxymethylstyrene(26) in the presence of a carbodiimide forming a phosphoramidate bond.64 At the end of the synthesis this 66

66 67

68

59 6o

61 62

63 64

K. Shikama. Arch. Biochem. Biophys., 1971, 147, 311. D. Perahia, B. Pullman, and A. Saran, Biochem. Biophys. Res. Comm., 1972,47, 1284. 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. R. di Sanseverino, Nature, 1970, 225, 333. K. L. Agarwal, A. Yamazaki, P. J. Cashion, and H. G. Khorana, Angew. Chem. Internat. Edn., 1972, 11, 451. H. Hayatsu and H. G. Khorana, J. Amer. Chem. SOC.,1967, 89, 3880. V. K. Potapov, 0. G. Chekhmakheva, Z. A. Shabarova, and M. A. Prokof‘ev, Doklady Akad. Nauk S.S.S.R., 1971, 196, 360 (Chem. Abs., 1971, 75,49481). V. F. Zarytova, V. K. Potapov, Z. A. Shabarova, and D. G. Knorre, DokZady Akad. Nauk S.S.S.R., 1971, 199, 1072 (Chem. Abs., 1972,76,4108). M. M. Kabachnik, V. K. Potapov, Z. A. Shabarova, and M. A. Prokof’ev, Doklady Akad. Nauk S.S.S.R., 1971,201, 858, (Chem. Abs., 1972,76, 113480). K. F. Yip and K. C. TSOU, J. Amer. Chem. SOC., 1971, 93, 3272; K. K. Ogilvie and K. Kroeker, Canad. J. Chem., 1972,50, 1211. E. Ohtsuka, S. Morioka, and M. Ikehara, J. Amer. Chem. SOC., 1972, 94, 3229.

154

Organophosphorus Chemistry

bond is cleaved with isoamyl nitrite; the mild conditions used in the last stage avoid the possibility of depurinization or randomization of the internucleotide bonds in polyribonucleotides. Silica,65Sephadex LH 20,6sand poly(ethy1ene glycol) 67 have all been tried as insoluble carriers in polynucleotide synthesis. Chlorination of nonporous glass beads or silica gel activates the surface to which nucleotides and nucleosides can be attached. However, the lability of Si-0-C and Si- 0- P bonds renders this approach unsuitable for nucleotide synthesis. On the other hand, silica gel bearing trityl chloride residues has been used to prepare dimeric Nucleotides have been bound through their phosphoryl groups to hydroxy-groups in Sephadex LH 20 and oligomers synthesized on this support. After the synthesis is complete, the cishydroxy-groups of the Sephadex facilitate the release of the oligomers.66 One advantage of low-molecular-weight poly(ethy1ene glycol) as a support in oligonucleotide synthesis is that it is soluble and all reactions can be carried out in Both nucleosides and nucleotides can be bound to poly(ethy1ene glycol) and in the latter instance adjacent hydroxy-groups again can assist in the removal of the product from the carrier when the synthesis is complete. The phosphotriester method has been successfully used in the synthesis 71 The of U P U P U , ~UpUpUpU,6g ~ and other di- and tri-ribonucle~tides.~~~ phosphotriester intermediates, in which not only the phosphoryl but also the sugar hydroxy-groups are protected by lipophilic groups, can be purified on a large scale using silical-gel chromatography. In general, the phosphoryl hydroxy-groups are protected by alkali-labile aryl 70 or trichloroethyl groups,71 whereas the sugar hydroxyls are protected by acid-labile tetrahydropyranyl or acetal derivatives (27).6s

In a study on the potential of a series of substituted trityl groups in oligonucleotide synthesis,72 the (p-bromophenacyloxypheny1)diphenylmethyl group (28) appeared to have several advantages. On account of its size the chloride derived from (28) reacted only with 5'-hydroxy-groups of nucleosides and could easily be removed by the action of zinc and acetic 65 66

67 68

69

70

'l 72

H. Koster, Tetrahedron Letters, 1972, 1527. H. Koster and K. Heyns, Tetrahedron Letters, 1972, 1531. H. Koster, Tetrahedron Letters, 1972, 1535. J. H. van Boom, P. M. J. Burgers, G. R. Owen, C. B. Reese, and R. Saffhill, Chem. Comm., 1971, 869. J. Smrt, Coll. Czech. Chem. Comm., 1972, 37, 846. T. Neilson and E. S. Werstiuk, Canad. J. Chem., 1971, 49, 3004. E. S. Werstiuk and T. Neilson, Canad. J. Chem., 1972, 50, 1283. A. Taunton-Rigby, Y.-H. Kim, C. J. Crosscup, and N. A. Starkovsky, J . Org. Chem., 1972, 37, 956.

Phosphates and Phosphonates of Biochemical Interest Br

0

155

Ph

C O C H 2 0 0 i Ph

(28)

acid. In acetic acid alone, (28) was not removed at an appreciable rate from nucleosides. The 2-phenylmercaptoethyl group (29) has been put forward as a protecting group for phosphate esters;73oxidation of the sulphide to the sulphoxide makes this protecting group alkali-labile 74 (Scheme 3). 0 11 PhSCH2CH20P< (29)

NaIO,

0 0 f II PhSCH,CH,OP<

f+

Scheme 3

HO-

NN-Dimethyl-p-phenylenediamine(30) has been attached to nucleotides to form basic phosphor amid ate^.^^ These have been polymerized and the products purified by using a cationic rather than an anionic ion-exchange 0 It

Me

H-P

<

resin. The protecting groups can be removed with hot acetic acid, conditions which may be too severe for purine-containing nucleotides. Isoamyl nitrite should be a mild method for cleaving the phosphoramidate bond and should be preferable to acidic treatment in this case. A number of polynucleotides containing atypical bases have been prepared during the past year either by polymerizing ribonucleoside diphosphates with polynucleotide phosphorylase 76--8 or by polymerizing 73 74

n 76

77

'*

R. H. Wightman, S. A. Narang, and K. Itakura, Canad. J. Chem., 1972, 50, 456. S. A. Narang, K. Itakura, and R. H. Wightman, Canad. J . Chem., 1972, 50, 769. T. Hata, K. Tajima, and T. Mukaiyama, J. Amer. Chem. SOC.,1971, 93, 4928. M. Ikehara and M. Hattori, Biochim. Biophys. Acta, 1972, 269,27. P. F. Torrence, J. A. Waters, and B. Witkop, J. Amer. Chem. SOC.,1972, 94, 3638. M. Ikehara and M. Hattori, Biochemistry, 1971, 10, 3585.

Organophosphorus Chemistry

156

ribo- and deoxyribo-nucleoside triphosphates with the corresponding p o I y m e r a ~ e . ~ 5’-Amino-5’-deoxythymidine ~-~~ 5’-N-triphosphate (31), a thymidine triphosphate analogue, can be polymerized using E. coli DNA polymerase I to give a product which possesses internucleotide phosphoramidate bonds ;83 the latter are, not surprisingly, acid-labile. 0 0 0

II

II II

HO-POPOP-N HO OH

HO

I-I

Oligoguanylic acids have been prepared from the 2’,3’-cyclic phosphates with the aid of RNase TI 84 and oligomers of 8-bromoguanylic acid have been obtained in this way.85 The latter are unobtainable by the polymerization of 8-bromoguanosine diphosphate 86 or triphosphate as these substrates adopt the unfavourable syn-conformation. The preparation of polynucleotides with a specific nucleotide incorporated at the 3’-end of the polymer has been achieved with dADP,87 2’(3’)-0isovaleryl-,8s or 2’(3’)-0-(a-methoxyethyl)-nucleoside 89 diphosphates and polynucleotide phosphorylase. The enzyme from Micrococcus Zuteus will catalyse the addition of a single dAMP residue to the 3’-hydroxyl of oligo-rA but further addition of dAMP residues takes place extremely slowly.87 The de nouo polymerization of ADP by polynucleotide phosphorylase is inhibited by dADP and this inhibition is relieved by oligo-rA. This has been taken to suggest that dADP interacts with the enzyme at the chain-initiation However, copolymers containing dAMP and AMP residues have been ~ b t a i n e d .Addition ~~ of bulky ester or ether 89 groups to the 2’(3’)-hydroxy-groups of a nucleoside diphosphate allow one nucleotide residue to be incorporated into a growing oligonucleotide but prevent further incorporation of nucleotide residues. After isolation of the oligonucleotides, the protecting groups can be removed by acidicE9or a1kaline treatment. 7g

8a

83 84 85

87 88

D. C. Ward and E. Reich, J. Biol. Chem., 1972, 247, 705. G. R. Banks, D. M. Brown, D. G. Streeter, and L. Grossman, J . Mol. Biol., 1971, 60, 425. A. G. Lezius and U. Rath, European J. Biochem., 1971, 24, 163. H. Beikirch and A. G. Lezius, European. J . Biochem., 1972, 27, 381. R. L. Letsinger, J. S. Wilkes, and L. B. Dumas, J. Amer. Chem. SOC.,1972, 94, 292. M. J. Rowe and M. A. Smith, Biochim. Biophys. Acta, 1971, 247, 187. R. Yuki and H. Yoshida, Biochim. Biophys. A d a , 1971, 246, 206. M. Ikehara, I. Tazawa, and T. Fukui, Biochemistry, 1969, 8, 736. J. Y. Chou and M. F. Singer, J. Biol. Chem., 1971, 246, 7486. G. Kaufmann, M. Fridkin, A. Zutra, and U. Z. Littauer, Euopean J. Biochem., 1971, 24, 4.

89

ao 91

J. K. Mackey and P. T. Gilham, Nature New Biol., 1971, 233, 551. J . Y.Chou and M. F. Singer, J . Biol. Chem., 1971, 246, 7497. J. Y.Chou and M. F. Singer, J . Biol. Chem., 1971, 246, 7505.

Phosphates and Phosphonates of Biochemical Interest

157

The sequencing of bacteriophage RNA has been reviewedg2 and improved methods for sequencing DNA have been developed. One promising approach depends on the insertion of ribonucleotides into DNA during synthesis by DNA polymerase I.93If a ribonucleotide triphosphate is used in addition to the three other deoxyribonucleotide triphosphates the enzyme will copy accurately a template in the presence of bivalent manganese cations. DNA-like material is obtained which can be cleaved by RNase to give oligomers which terminate at the 3’-end in ribonucleotides. Another approachg4 to DNA sequencing makes use of the ability of terminal deoxynucleotidyl transferase to add ribonucleotides to oligodeoxyribonucleotide primers. Partial degradation of a polydeoxyribonucleotide with snake venom phosphodiesterase gave a mixture of oligomers which were treated without separation with 32P-labelledATP and the transferase. The resulting oligomers which now possessed a 32P-labelledAMP residue at the 3’-end were then separated and degraded with spleen phosphodiesterase. Hence the 32P-labelwas transferred to the nearest neighbour of the AMP residue, enabling the nucleotide at the 3’-end of each oligodeoxyribonucleotide to be determined. A third sequencing method is based on the exonucleolytic degradation of linear duplex DNA by bacteriophage T4 DNA polymera~e.~ If~a single deoxynucleoside triphosphate is added to the enzymic reaction mixture the exonucleolytic activity of the enzyme is suppressed and only a few nucleotide residues are released. In this way information is obtained on the base sequence at the end of the DNA molecules. Polynucleotide ligase from E. coli which have been infected with bacteriophage T4 reacts with ATP to form an isolable AMP-ligase complex.gs When this complex is incubated with duplex DNA containing single strand breaks, the AMP residue is transferred to the 5’-phosphoryl group at the break with the formation of a pyrophosphate bond. Chain repair of the DNA takes place by the 3’-hydroxy-group at the break attacking this pyrophosphate with the release of AMP. Homopolynucleotides which have been covalently bound to cellulose have been used for the chromatographic isolation of globin mRNA 97 and other RNAsg8,99 which are rich in sequences of the complementary nucleotide. The isolation of poly A using untreated cellulose has also Da

D3

94

D5

D6

F. Sanger, Biochem. J., 1971, 124, 833. W. Salser, K. Fry, C. Brunt, and R. Poon, Proc. Nut. Acad. Sci. U.S.A., 1972, 69,

238.

R. Roychoudhury, D. Fischer, and H. Kossel, Biochem. Biophys. Res. Comm., 1971,

45, 430.

P. T. Englund, J. Biol. Chem., 1971, 246, 3269. C. L. Harvey, T. F. Gabriel, E. M. Wilt, and C. C. Richardson, J. Biol. Chem., 1971,

246,4523.

D8

H. Aviv and P. Leder, Proc. Nut. Acad. Sci. U.S.A., 1972, 69, 1408. M. Edmonds, M. H. Vaughan, jun., and H. Nakazato, Proc. Nat. Acad. Sci. U.S.A.,

D9

R. Sheldon, C. Juvale, and J. Kates, Proc. Nut. Acad. Sci. U.S.A., 1972, 69, 417.

n7

1971, 68, 1336.

158

Organophosphorus Chemistry

been reported.loO The homopolynucleotides can be attached through their 5'-phosphoryl groups to the cellulose using a carbodi-imide ;lol alternatively pyrimidine polynucleotides can be attached to cellulose following U.V. i r r a d i a t i ~ n .In ~ ~this case, irradiation of the pyrimidine ring must lead to free radicals being formed at the 5- and 6-positions in the ring which can then react with the cellulose. Polyinosinic acid (polyrI) has been covalently bound through its terminal 5'-phosphoryl group to Sepharose and then annealed with polycytidylic acid (poly rC).lo2 The bound poly rI/rC renders cells resistant to viral infections, as does the comparable hybrid in which the poly rC is bound to Sepharose and the poly rI annealed to it. However, insolubilized poly rI/rC is hydrolysed to an appreciable extent during the biological assay and it is possible that the degraded, soluble nucleotides make the cells resistant to viral infection. An assay for polynucleotide ligase has been described lo3 which employs poly dA/dT covalently linked to cellulose through the poly dT chain. Oxidation of RNA with periodate gives a 2',3'-dialdehyde which can react with hydrazino-groups attached to agarose to insolubilize the RNA.Io4 Analytical Techniques and Physical Methods.-The mapping of oligonucleotides and nucleic acid digests on cellulose lo5 or cellulosepolyethyleneimine lo6 has been described recently, and columns of mercurated dextran lo' or dihydroxyborylcelluloselo* have been used to fractionate nucleotide mixtures. Electrophoresis on polyacrylamide gels has been advocated as a rapid method for desalting and fractionating mixtures of oligonucleotides.10g The slP n.m.r. spectra of E. coli tRNAgIUand yeast tRNAphe are similar but distinct.l1° The spectra change with changing pH or on melting the nucleic acids and evidence has been obtained for the specific binding of magnesium cations to the tRNAs. 3 Coenzymes and Cofactors Nucleoside Diphosphate Sugars.-The biosynthesis of saccharides from sugar nucleotides has recently been reviewed.lll The incorporation of monosaccharides into bacterial cell walls involves the participation of 100 101 102

P. A. Kitos, G. Saxon, and H. Amos, Biochem. Biophys. Res. Comm., 1972,47, 1426. P. T. Gilham, J. Amer. Chem. SOC.,1964, 86, 4982. A. F. Wagner, R. L. Bugianesi, and T. Y. Shen, Biochem. Biophys. Res. Comm., 1971,

45, 184.

U. Bertazzoni, F. Campagnari, and U. De Luca, Biochim. Biophys. Acta, 1971,240,515. D. L. Robberson and N. Davidson, Biochemistry, 1972, 11, 533. l o 6 K. W. Mundry and H. Priess, Biochim. Biophys. Acta, 1972, 269,225. lo6 E. M. Southern and A. R. Mitchell, Biochem. J., 1971, 123, 613. lo' D. W. Gruenwedel and J. C. C. Fu, Proc. Nut. Acad. Sci. U.S.A., 1971, 68, 2002. l o 8 M. Rosenberg and P. T. Gilham, Biochim. Biophys. A d a , 1971, 246, 337. lo9 H. Birnboim, Biochim. Biophys. Acta, 1972, 269, 217. M. GuBron, F.E.B.S. Letters, 1972, 19, 264. 111 H. Nikaido and W. Z. Hassid, Adu. Carbohydrate Chem., 1971, 26, 352. lo3

lo4

Phosphates and Phosphonates of Biochemical Interest

159

polyprenol phosphates as acceptors of sugar residues,l12 and similar polyprenol intermediates have been implicated in glycoprotein biosynthesis.lls For example, dolichol monophosphate (32) can act as a mannose acceptor 0

II H?CH2C (Me) =CHCH2)TVCH,CH( Me)CH,CH,OP -OH I OH

in liver 114or in S. cerevisiae 115 and polyprenol phosphates are involved in GDP-mannose metabolism in A. niger 116and Phaseolus a u r e u . ~ Incuba.~~~ tion of dolichol monophosphate glucose with liver microsomes produces a polysaccharide which is joined to dolichol by either a phosphate or a pyrophosphate group.l18 The enzymic epimerization of UDPGal requires NAD+ as a cofactor ll8 and the NAD+ is reduced during the reaction.120 UDP-4-ketoglucose (33) is an intermediate in this epimerization lal as was originally postulated.120 The conversion of UDPGlc to UDP-glucuronic acid requires two equivalents of NADf, and UDP-a-D-glucohexodialdose [UDPGlc-6-CHO (34) ]

Ho

OPPR

OPPR

CHO

HO* Ho

Ho

OPPR

which has recently been synthesized enzymically is an intermediate in this oxidation.122 The first step in the overall conversion, the oxidation of UDPGlc to (34), is reversible whereas the second oxidation step appears to be rate-limiting as (34)and UDPGlc are oxidized to UDP-glucuronic M. J. Osborne, Ann. Rev. Biochem., 1969, 38, 501. N.H.Behrens and L. F. Leloir, Proc. Nat. Acud. Sci. U.S.A., 1970, 66, 153. 11* J. B. Richards, P. J. Evans, and F. W. Hemming, Biochem. J., 1971, 124, 957. 115 W.Tanner, P. Jung, and N. H. Behrens, F.E.B.S. Letters, 1971, 16, 245. 116 R. M. Barr and F. W. Hemming, Biochem. J., 1972, 126, 1203. 112 113

117

S. S. Alam and F. W. Hemming, F.E.B.S. Letters, 1971, 19, 60. N. H. Behrens, A. J. Parodi, and L. F. Leloir, Proc. Nat. Acad. Sci. U.S.A., 1971, 68, 2857.

E. S. Maxwell, J . Biol. Chem., 1957, 229, 139. D.B. Wilson and D. S. Hogness, J. Biol. Chem., 1964, 239, 2469. U.S. Maitra and H. Ankel, Proc. Nut. Acad. Sci. U.S.A., 1971, 68, 2660. lZ2 G. L. Nelsestuen and S. Kirkwood, J. Biol. Chem., 1971, 246, 3828.

llD

lZo 121

160

Organophosphorus Chemistry

acid at the same rate. UDP-L-arabinose, which has been synthesized by the phosphoromorpholidate method, is identical with the product which is formed in plants from UDP-glucuronic acid or UDP-xy10pyranose.l~~ of pyridoxol and Vitamin B6 and Related Compounds.-Analogues pyridoxal phosphates in which the 5’-methylene (35) or the 5’-phosphate group (36) have been modified have been used to study the substrate specificity of pyridoxine phosphate oxidase.lZ4 The methylene analogues acted as substrates whereas (36) or the 2-cyanoethyl ester of pyridoxol

phosphate did not act as substrates for the enzyme. A pyridoxol phosphonate (37), which was prepared by a modified Wittig reaction from the aldehyde (38), exhibited antivitamin B6 activity in a microbiological assay.126 Pyridoxal phosphate is an essential cofactor for many phosphorylases,lZ6 but whereas pyridoxal phosphate monomethyl ester and the 3’-O-methyl ether bind to apophosphorylase b, the reconstituted enzyme has no activity.lZ7 Some activation of apophosphorylase b is observed with the N-oxide of pyridoxal phosphate (39), but this appears to be due to a deoxygenation reaction which is catalysed by the enzyme and which produces the pyridoxal phosphate. Apophosphorylase b which had been

lZ3 125

lZ6

12’

G. 0. Aspinall, I. W. Cottrell, and N. K. Matheson, Canad.J . Biochem., 1972,50, 574. W. Korytnyk, B. Lachmann, and N. Angelino, Biochemistry, 1972, 11, 722. R. F. Struck, Y. F. Shealy, and J. A. Montgomery, J. Medicin. Chem., 1971, 14, 568. T. Baranowski, B. Illingworth, D. H. Brown, and C. F. Cori, Biochim. Biophys. Acta, 1957, 25, 16. T. Pfeuffer, J. Ehrlich, and E. Helmreich, Biochemistry, 1972, 11, 2125.

Phosphates and Phosphonates of Biochemical Interest

161

reconstituted by pyridoxal phosphate monomethyl ester had physical properties which were very similar to the natural enzyme even though the former was inactive.128 This suggests that pyridoxal phosphate has some function in determining the structure of phosphorylases as well as acting in some catalytic manner. Pyridoxamine phosphate is a cofactor in the reduction of CDP-4-keto-6-deoxy-~-glucose to CDP-4-keto-3,6dideoxy-D-glucose ;Izs the mechanism of this reaction is, however, obscure, although it does not appear to involve a transamination step. The aldehyde group in pyridoxal phosphate is a useful ‘handle’ for attaching this molecule to an insoluble support for use in affinity chromatography. If Sepharose is first activated with cyanogen bromide and then treated with 1,6-diaminohexane, a modified Sepharose is obtained which will react with the aldehyde group of pyridoxal phosphate to give a Schiff base (Scheme 4). Reduction of the C=N group of the Schiff base with Sepharose

i, BrCN ii, H,N(CH,),NH,

’ @NH(CH,),NH,

CH,0P03H, @-NH(CH,,,N=CH

0

/

1 (

L

HO

Me

C,H,0P03H2

@-NH(CH,),NHCH,

-

HO

Me Scheme 4

borohydride gives covalently bound pyridoxal phosphate in which all substituents of the pyridine ring are available for binding to a p o e ~ y m e s . ~ ~ ~ Apotransaminases have been isolated and purified using pyridoxalSepharose as a support in affinity chromatography. Other Cofactors.-NAD+ which has been attached to glass by a diazo-coupling procedure probably through C-8 of the adenine ring 131 las

lZB

130 131

T. Pfeuffer, J. Ehrlich, and E. Helmreich, Biochemistry, 1972, 11, 2136. E. Ryan and P. F. Fottrell, F.E.B.S. Letters, 1972, 23, 73. P. Gonzalez-Porque and J. L. Strominger, Proc. Nat. Acad. Sci. U.S.A., 1972,69,1625. M. K. Weibel, H. H. Weetall, and H. J. Bright, Biochem. Biophys. Res. Comm., 1971, 44,347.

162

Organophosphorus Chemistry

functions as a coenzyme for yeast alcohol dehydrogenase. Another method of linking NAD+ to an insoluble support consists of coupling the coenzyme with the aid of DCC to Sepharose which has been modified by treating it first with cyanogen bromide and then with 6-aminohexanoic 132 The site of attachment of the aminohexanoic acid groups to the NAD+ is unknown, but ribose hydroxy-groups may be involved. Direct coupling of NAD+ to cyanogen bromide-activated cellulose does not give an active A column of Sepharose-bound NAD+ product despite previous will separate a mixture of serum albumen, glyceraldehyde 3-phosphate dehydrogenase, and lactate dehydr~genase.~~ Thiamine pyrophosphate is formed by the direct transfer of a pyrophosphoryl group from ATP to thiamine.134 This reaction is unusual as it is one of the few examples of a pyrophosphoryl group being transferred from ATP in one step. Enzyme systems which will catalyse the formation of thiamine pyrophosphate from thiamine in two stages have now been detected in E. coZi 136 and The phosphorylation reactions appear to follow a more usual course and thiamine monophosphate is an intermediate in a two-stage reaction. The assignment of the stereochemistry of a number of analogues of phosphoenol pyruvate [PEP (40;R1 = R2 = R3 = R4 = H)] has been made by lH n.m.r. spectroscopy.138 No partially or fully esterified derivatives of PEP, e.g. (40; R1 = R4 = H, R2 = R3 = Me), could act as substrates for pyruvate kinase but some activity was found with analogues with small substituents in the 3-position, e.g. (40; R1 = Me or Br, R2 = R3 = R4 = H), in contrast to earlier (Z)-Phospho135s

OP0 -O?cx H' .Me

l32 133 134

135

136 13' 138

13s

q3-

"

+

ADP

ruvate kinase D20-Mg'+

H T M e

+

ATP

co

K. Mosbach, H. Guilford, P. 0. Larsson, R. Ohlsson, and M. Scott, Biochem. J., 1971, 125, 20P. C. R. Lowe and P. D. G. Dean, F.E.B.S. Letters, 1971, 14, 313. G.W. Camiener and G. M. Brown, J. Biol. Chem., 1960,235,2411. H.Nishino, A. Iwashima, and Y . Nose, Biochem. Biophys. Res. Comm., 1971,45, 363. A. Iwashima, H. Nishino, and Y . Nose, Biochim. Biophys. Acta, 1972,258, 333. D. W.Hutchinson and C. W. K. Lam, unpublished observations. J. A. Stubbe and G. L. Kenyon, Biochemistry, 1971,10, 2669. A. E. Woods, J. M. O'Bryan, P. T. K. Mu, and R. D. Crowder, Biochemisrry, 1970, 9,2334.

163

Phosphates and Phosphotiates of Biochemical Interest

enol-a-ketobutyrate (41) is converted by pyruvate kinase into (3R)a-keto[3-2H]butyrate (42) :138 hence the deuterium must add stereospecifically at C-3 on the 2-si,3-re face of (41).140 These results are in accord with earlier observations on the stereochemistry of the reaction of PEP with pyruvate kinase.141 The enzymatic synthesis of 5-enolpyruvylshikimate 3-phosphate (43) from PEP and shikimate 3-phosphate occurs with C - 0 cleavage of the PEP, and when the reaction was carried out in deuterium oxide as solvent, 53% monodeuterio- and 39% dideuterio-(43) were A

@O’.’

YoPo:- 617% bOH ,

+

J

c02-

OH

CO2-

80.” .

//

0-c -OPO,? -

OH

OH (43)

reversible addition-elimination reaction has been proposed to account for these observations. The rate of hydrolysis of acetyl dimethyl phosphate in the pH range 2-7 is some four orders of magnitude greater than that observed for acetyl phenyl phosphate under comparable conditions, although the two compounds are subject to similarly directed isotope effects and methanolysis of both compounds leads to methyl The great dependence of the rate of hydrolysis on the pK, of the leaving group suggests that the transition state for departure is far along the reaction co-ordinate. Since an electrostatically neutral form of acetyl phosphate is a much better acylating agent than an anionic form, if groups on the surface of an enzyme can neutralize the acidic groups of PEP, then enhanced reactivity of the coenzyme should be observed. A detailed study of the kinetics of acyl phosphate hydrolysis by muscle acyl phosphatase has led to development of a chemical mechanism for the enzymic catalysis which differs significantly from those for the non-enzymatic hydrolysis of acetyl The substrate 140 141 142 143 144

K. R. Hanson, J. Amer. Chem. SOC.,1966, 88, 2731. I. A. Rose, J. Biol. Chem., 1970, 245, 6052. W. E. Bondinell, J. Vnek, P. F. Knowles, M. Sprecher, and D. B. Sprinson, J. Biol. Chem., 1971, 246,6191. R. Kluger and P. Wasserstein, Biochemistry, 1972, 11, 1544. D. P. N. Satchell, N. Spencer, and G. F. White, Biochim. Biophys. Acta, 1972,268, 233.

1 64

Organophosphorus Chemistry

group is held to the enzyme surface primarily by the phosphate group through three of the phosphate oxygen atoms. The bound acyl phosphate then undergoes slow nucleophilic attack by an adjacent water molecule (Scheme 5). 0

slow

RC02-

R-C,

,o,

0=P' 'H / \ -0 0-

t

H-X-

0

I

fast

HO-P-OH / \

0

RC0,H

+

0 //

0-

X-

+

€1. PO.,?-

+

BH

Scheme 5

Biotin carboxylase, an enzyme which catalyses the carboxylation of' biotin in E. coli, will catalyse the transfer of phosphate from carbamyl phosphate (44) to ADP.146 Carbonyl phosphate (45), but not acetyl phosphate, can replace (44)in this system, and this has been taken to imply that the carboxylation of biotin is not a concerted reaction but that (45) is an intermediate in this process. 145

S. E. Polakis, R. B. Guchhait, and M. D. Lane, J. Biol. Chem., 1972, 247, 1335.

Phosphates and Phosphonates of Biochemical Interest NHzCO.OPO,H, (44)

165

HOCO .OPO,H, (45)

4 Naturally Occurring Phosphonates In Tetrahyrnena pyriformis the radioactive carbon atom in phosphoenol [3-14C]pyruvate is incorporated into the phosphonate carbon atom in 2-aminoethylphosphonic acid (46),146 contirming an earlier suggestion 147a that an intramolecular rearrangement of PEP takes place during the biosynthesis of (46). The incorporation of label into (46) is inhibited to a greater extent by phosphonoacetaldehyde (47) than by 2-amino-3phosphonopropionic acid (48): hence the latter may not be on the main

*

NH2CHzCHzP(O)(OH)2

biosynthetic pathway to (46). The product initially formed by the intramolecular rearrangement of PEP is probably decarboxylated to (47) before amination to (46) occurs and the latter is then incorporated into phosphonolipids. This biosynthetic scheme for phosphonolipids differs from an earlier scheme147bin which (46) was incorporated into the phosphonolipids before decarboxylation took place. The chemical shifts of phosphonates in 31Pn.m.r. spectra are considerably different from those of phosphates, and with the advent of signal-enhancing techniques, 31Pn.m.r. spectroscopy appears to be an ideal method for the determination of the relative amounts of phosphonates present in biological systems. Spectroscopic methods are preferable to those based on the 146

14'

M. Horiguchi, Biochim, Biophys. Acta, 1972, 261, 102. W. A. Warren, Biochim. Biophys. Acta, 1968, 156, 340; (b) C. R. Liang and H. Rosenberg, Biochim. Biophys. Acta, 1968, 156, 437.

(a)

166

Organophosphorus Chemistry

resistance of the C-P bond towards hydrolysis, owing to the unexpected lability of some phosphonates, e.g. (47). An estimate of the amount of phosphonates occurring in sea anemones has been made by 31Pn.m.r.14* and it is of interest that discrete bands were observed within the phosphate and phosphonate regions of the spectrum. This effect may be due to the presence of choline phospho- and phosphono-lipids, as the quaternary nitrogen atom of choline may cause a shift in the phosphorus resonance. Syntheses of epoxyphosphonates related to phosphonomycin (49) continue to be developed. In one synthetic scheme dimethyl hydroxymethylphosphonate is treated with acetaldehyde in the presence of 0

II

HOCH2P(OMe)2

MeCHO-HCI

0

II

MeCHCIOCH,P(OMe),

0 (49)

hydrochloric acid to give the chloride which is dehydrochlorinated and then treated with a diacyl peroxide to give the dimethyl ester of (49).149 Other epoxyphosphonates with antibacterial activity, (50) and (5 l), have 161 been prepared by the epoxidation of vinylphosphonic

5 Oxidative Phosphorylation Oxidation of thiols or disulphides in pyridine solution in the presence of ADP and inorganic phosphate by two equivalents of iodinelSa or bromine153leads to the formation of ATP. The initial reaction between the disulphide and positive halogen is presumably followed by the displacement of halide by phosphate ion to give a phosphorylating species (52). ADP would react with (52) with the formation of ATP and a thiosulphinic 148 149

150

151

l68

T. 0. Henderson, T. Glonek, R. L. Hilderbrand, and T. C. Myers, Arch. Biochem, Biophys. 1972,149,484. R. A. Firestone and M. Sletzinger, U.S.P. 3 584 014 (Chem. Abs., 1971, 75, 63 977). B. G. Christensen and L. D. Cama, G. P. 2002415 (Chern. Abs., 1971, 7 5 , 77 031). B. G. Christensen and W. J. Leanza, B.P. 1 244 910 (Chern. Abs., 1971,75, 129 940). E. BSiuerlein, M. Klingenfuss, and T. Wieland, European J. Biochem., 1971, 24, 308. T. Wieland and E. Bauerlein, Angew. Chem. Internat. Edn., 1968, 7 , 893.

167

Phosphates and Phosphonates of Biochemical Interest

ester (53). Attack on the latter by inorganic phosphate leads to a mixed anhydride (54) which could function as a phosphorylating agent. Alternatively, attack by phosphate ion on the initial adduct would lead to (54) RSSR

+

Pi

RSgR ----+ RSSR I I

Hal’

lpi I

ATP

+

RS0,-

ADP

0

Pi

RSOPO,H, +--( 54)

RSsR

+ 0

+

ATP

and a sulphenyl halide. Haemin in the presence of oxygen can also function as an oxidizing agent in this system. This oxidative synthesis of ATP has also been reported to occur in buffered aqueous systems if glutathione and cytochrome c are used.lS4 In this last reaction the synthesis of ATP has now been shown lS6to be due to the disproportionation of two molecules of ADP, and in pyridine solution haemin in the absence of thiols can cause the disproportionation of ADP.153 The formation of sulphenic-phosphoric anhydrides156 in aqueous solution is unlikely owing to the extreme instability of these anhydrides in such an Phosphoroimidazoles have been suggested lS8 as possible intermediates in mitochondria1 oxidative phosphorylation, and it has been claimed 150 that irradiation of a solution of imidazole, haematoporphyrin, and phosphate leads to phosphoryl transfer. However, repetition 160 of this experiment using radioactive imidazole failed to show the formation of imidazole phosphate, although cyclization of adenosine 2’(3’)-phosphate was observed. 6 Sugar Phosphates

The syntheses of various glycosyl phosphates have been described in detail,lsl as has the phosphorylation of 5,6-O-isopropylidene-~-ascorbic 164

lS6

166

16’

lS8 lSD

160

A. A. Painter and F. E. Hunter, jun., Biochem. Biophys. Res. Comm., 1970, 40, 369. E. Bauerlein, Biochem. Biophys. Res. Comm., 1972, 47, 1088. A. A. Painter and F. E. Hunter, Biochem. Biophys. Res. Comm., 1970, 40, 387. D. 0. Lambeth and H. A. Lardy, Biochemistry, 1969, 8, 3395. J. H. Wang, Science, 1970, 167, 25. S. I. Tu. and J. H. Wang, Biochemistry, 1970, 9, 4505. M. J. Bishop, Biochim. Biophys. Acta, 1972, 267, 435. ‘Methods in Carbohydrate Chemistry,’ ed. R. L. Whistler and J. N. Be Miller, Academic Press, London, 1972, vol. VI.

168

Organophosphorus Chemistry

acid using phosphoryl chloride in aqueous pyridine.162 In the latter reaction, the 3-phosphate is the only product. Tervalent phosphorus acids and their esters not only esterify but also dehydrate xylitol, leading to a complex mixture of From a 31Pn.m.r. study of D-fructose 1,6-diphosphate and stereochemical analogues, it appears that the /3-furanose form (55) of fructose 1,6-diphosphate predominates in aqueous

,

H?O,P o H CY

\>o

H CH,OPO,H,

HO (55)

s01ution.l~~This observation is in agreement with the results obtained from an earlier n m r . but is in direct contradiction to conclusions based on U.V. spectroscopy.166 Even though the keto-form of (55) is an obligatory intermediate in many enzymic reactions only minute amounts are present in aqueous solution under normal conditions. From the reaction between fructose 1,6-diphosphatase and structural analogues of (%),la'it has been deduced that the furanose ring and the C-3 and C-4 hydroxy-groups of (55) are essential for activity. Oxidation of D-glucuronic acid 6-phosphate by vanadium pentoxide and chlorate ion gives ~-ara.-hex-2-ulosonic acid 6-phosphate (56), which is a known intermediate in carbohydrate metabolism.ls8 In the presence of alkali, (56) is unstable and breaks down by a retro-aldol reaction to a triose phosphate. CO,H I

co

I I HCOH I HCOH I

HOCH

OH-

CHO I HCOH

I

CH,OPO,H,

CH,0P03H,

(56) H. Nomura, M. Shimomura, and S. Morimoto, Chem. andPharm. Bull. (Japan), 1971, 19, 1433. l e 3 E. E. Nifant'ev, L. T. Elepina, and V. N. Bakakhontseva, Zhur. obshchei Khim., 1971, 41, 707 (Chem. Abs., 1971,75, 64 140). 164 G. R. Gray, Biochemistry, 1971, 10, 4705. l65 G. R. Gray and R. Barker, Biochemistry, 1970, 9,2454. 186 G. Avigad, S. Englard, and I. Listowsky, Carbohydrate Res., 1970, 14, 365. 167 S. J. Benkovic, J. J. Kleinschuster, M. M. deMaine, and I. J. Siewers, Biochemistry, 1971,10,4881. 1e8 F. Trigalo and L. Szabb, European J . Biochem., 1972, 25, 336.

lli2

Phosphates and Phosphonates of Biochemical Interest

7H 2 0H

169

CH,OPO,H, I

OP0,H2

HO

HO

HO

(58)

(57)

The syntheses of sucrose 6’-pho~phate,l~~ methyl a-mannopyranoside

4- and 6-pho~phates,l~~ and 3-deoxy-3-fluoro-~-g~ucose 1- and 6-phosphates [ (57) and ( 5 8 ) ] 171have been described. Neither (57) nor (58) was a substrate for UDPGlc-pyrophosphorylase or phosphoglucomutase, although (58) was a poor substrate for glucose 6-phosphate dehydrogenase.171

7 Phospholipids D-1 -Deoxy- 1-fluoroglycerol 3-phosphate (59), a potential anticancer

agent,172 has been prepared from D-mannitol (60) by a stereospecific route which should be suitable for the synthesis of the L-isomer of (59).173Transformation of (60) into D-1-tosyl-2,3-O-isopropylideneglycerol, followed by displacement of tosyl ion by fluoride ion, removal of the isopropylidene group, and treatment with dibenzyl phosphorochloridate gave the dibenzyl ester of (59). A m-mixture of this dibenzyl ester was CH20H

CH20Ts

HO

-

i, KF ii, H 3 0 + i i i , phosphorylate

OH

18

CH,F

HtOH CH20P03H2

3 7 OCHZ

I 18H3’10CH I

CH, I ,oCHzP II ‘CH,CH2&Me3 0 (61) 169

170 171 i m

179

J. G. Buchanan, D. A. Cummerson, and D. M. Turner, Carbohydrate Res., 1972, 21, 283 (Chem. Abs., 1972, 76, 86038). T. N. Cawley and R. Letters, Carbohydrate Res., 1971,19,373 (Chem. Abs., 1971,75, 118 529). J. A. Wright, N. F. Taylor, R. V. Brunt, and R. W. Brownsey, J. C . S. Chem. Comm., 1972, 691. T. P. Fondy, G. S. Ghangas, and M. J. Reza. Biochemistry, 1970, 9, 3272. G. S. Ghangas and T. P. Fondy, Biochemistry, 1971, 10, 3204.

170 Organophosphorus Chemistry obtained from the reaction between epifluorohydrin and dibenzyl phosphoric acid. Diether phosphinate analogues of lecithin, e.g. (61), have also been prepared from (60).17* 2-Chloromethyl-4-nitrophenyl phosphorodichloridate (62) has been used as a bifunctional phosphorylating agent in the preparation of a-glycerophosphorylcholine (63).175The 2-chloromethyl4-nitrophenyl group is readily removed by treatment with aqueous pyridine ;

XI

o/

\OCH,CH,CI

i, C,H,N ii, Me,N iii, H:J) +

-

:o\/H

H

presumably displacement of the benzylic chlorine atom by pyridine is followed by the rapid decomposition of the quaternary compound (64). The synthesis of dl-a-tocopheryl phosphoric diesters using (62) has also been rep orted .l7 The use of arylsulphonyl chlorides in place of DCC in the synthesis of phosphatidyl cholines gives products with a higher molar rotation than has been obtained previ0us1y.l~~ Resolution of 1,2,4,5,6-penta-0-acetyl-myo-inositols has been achieved by means of their acid oxalates; selective removal of the oxalyl residues with base followed by phosphorylation of the hydroxy-groups with phosphoryl chloride and benzyl alcohol produced the dibenzyl phosphates of the inositol penta-acetates. Removal of the protecting groups liberated either 1-D-myo-inositol 1-phosphate (65) or the ~ - i s o r n e r . ~ ~ * 174

175

176 17'

178

A. F. Rosenthal, L. Vargas, and S. C. H. Han. Biochim. Biophys. Acta, 1972,260,369. Y . Mushika and N. Yoneda, Chem. and Pharm. Bull. (Japan), 1971, 19, 696. Y. Mushika and N. Yoneda, Chem. and Pharm. Bull. (Japan), 1971, 19, 687. R. Aneja and J. S. Chadha, Biochim. Biophys. Acta, 1971, 248, 455. J. G. Molotkovsky and L. D. Bergelson, Tetrahedron Letters, 1971, 4791.

171

Phosphates and Phosphonates of Biochemical Interest

Signals in the lH n.m.r. spectra of phosphatidylcholine residues are broadened 17g on the addition of the spin-labelled phosphatidylcholine (66).180 This has been interpreted as indicating that rapid diffusion occurs in the plane of the phosphatidylcholine bilayer as the broadening does not appear to be due to collision exchange of spin-label or fusion of the ve~ic1es.l~~ 31P Nuclear magnetic relaxation times have been determined using several phospholipid dispersions, and from the temperature dependence of the spin-spin relaxation times it has been concluded that these relaxation times reflect the mobility of the hydrophobic lipid head group.lS1 Bacterial glycophospholipidslE2and the metabolism and function of membrane phospholipids of E. coli lS3 have been reviewed.

8 Enzymology The use of paramagnetic probes in magnetic resonance studies on phosphoryl transfer enzymes, e.g. creatine kinase, has been reviewed,ls4 and model reactions with phosphoroguanidates have led to new ideas on the mechanism of action of this enzyme.lS5 The pH-rate profile for the

(67)

NMe,

I

Me R. D. Kornberg and H. M. McConnell, Proc. Nut. Acad. Sci. U.S.A., 1971, 68,2564. R. D. Kornberg and H. M. McConnell, Biochemistry, 1971, 10, 1111. m1 R. W. Barker, J. D. Bell, G. K. Radda, and R. E. Richards, Biochem. Biophys. Res. Comm., 1972,260, 161. 18* N. Shaw and A. Stead, F.E.B.S. Letters, 1972, 21, 249. la3 J. E. Cronan, jun., and P. R. Vagelos, Biochim. Biophys. Acta, 1972, 265, 25. la4 M. Cohn and J. Reuben, Accounts Chem. Res., 1971,4,214. P. Haake and G. W. Allen, Proc. Nut. Acad. Sci. U.S.A., 1971, 68, 2691. 170

la0

172

Organophosphorus Chemistry

hydrolysis of NN-dimethyl-N’-phosphoroguanidate(67) has a maximum at pH 2.0 and the rate of cleavage of the P-N bond in (67) is very high, suggesting that a metaphosphate intermediate may be involved in its reactions. Further support for the involvement of a metaphosphate in phosphoryl transfer from (67) comes from the indiscriminate phosphorylation of alcohol-water mixtures by this compound. It is suggested that the phosphorylation of ADP by phosphocreatine (68) catalysed by creatine kinase also proceeds by a metaphosphate intermediate and that the enzyme functions as a proton-transfer agent in the generation of this intermediate. A phosphoryl-enzyme intermediate is formed during reactions catalysed by alkaline phosphatase.lss 0-4-Nitrophenyl phosphorothioate is hydrolysed 1000 times more slowly by alkaline phosphatase than is its oxygen analogue, suggesting an &2(P) mechanism for the phosphorylation of the enzyme.ls7 From a kinetic study of the reaction between a series of alkyl-, aryl-, and arylamido-phosphates and alkaline phosphatase, it has been shown that steric factors are important in these reactions.la8 Moreover, although amidophosphates [e.g. (69) ] are substrates for this enzyme lg9

they react some 60000 times too slowly for an &1(P) mechanism, which is additional evidence for an &2(P) reaction. Covalent phosphorylenzyme intermediates have also been demonstrated recently for acid phosphatase,lgO acetate kinase,lgl and succinyl CoA synthetase from E. ~ 0 Z i . l ~A~ phosphopeptide containing 25 amino-acid residues and four of the five phosphorus atoms present in p-casein type A1 has been isolated from a tryptic digest of the protein.lg3 The phosphorus atoms are present as phosphoserine residues situated close together and it has been suggested that phosphoserines could be involved in phosphoryl transfer reactions. Under mild conditions, chloro- and bromo-acetol phosphates (70), reactive analogues of dihydroxyacetone phosphate, inactivate yeast fructose XCH,COCH ,OPO,H, (70) X = Br o r C1 J. H. Schwartz, Proc. Nat. Acad. Sci. U.S.A., 1963, 49, 871. I. Katz and R. Breslow, J. Amer. Chem. SOC.,1968, 90, 7376. lS8 A. Williams and R. N. Naylor, J . Chem. SOC.(B), 1971, 1973. lS8 S. L. Snyder and 1. B. Wilson, Biochemistry, 1972, 11, 1616. R. L. VanEtten and M. E. Hickey, Fed. Proc., 1972, 31,451Abs. lgl R. S. Anthony and L. B. Spector, J . Biol. Chem., 1972, 247, 2120. la2 T. Wang, L. JuraSek, and W. A. Bridger, Biochemistry, 1972, 11, 2067. lg3 W. Manson and W. D. Annan, Arch. Biochem. Biophys., 1971, 145, 16.

lS6

Phosphates and Phosphonutes of Biochemical Interest

173

diphosphate aldolase by alkylation of approximately one thiol group per molecule of catalytic subunit, probably near the active site of the enzymes.1s4 a-Glutamyl phosphate (7 l), a possible intermediate in reactions catalysed by glutamine synthetase,ln5cyclizes rapidly to a pyrrolidone (72) with expulsion of phosphate, which renders isolation of (71) difficult. However, when cis-l-amino-l,3-dicarbox~c~clohexane (73), which is an analogue of c02-

I CHz

H3N' C0,(71)

CO,H HQ)C (H , ~N"'

C0.0P03H2

HOC H ,(), ~ N . . (74)

(73)

glutamate, is incubated with glutamine synthetase and ATP, an enzymesubstrate complex can be isolated by gel-fi1trati0n.l~~An acidic compound which has the properties of the mixed anhydride (74) can be isolated from the complex. The effect of a number of oximes derived from pyridines on rat-brain acetyl cholinesterase which had been inactivated by isopropyl methylphosphonofluoridatehas been studied, the most effectiveat restoring enzymic activity being (75).ls7 Acetyl cholinesterase is also inhibited by aryl

2Br(75)

methylphosphonochloridates, both the reactivation and ageing of the enzyme being dependent on the substituents on the aromatic ring.ls8 Reactivation of the phosphonylated enzyme is due to hydrolysis of the phosphonoserine bond, and since substitution in the aryl group of aryl methylphosphonochloridates would have an effect on the electrophilicity of the phosphonyl group, the rate of reactivation would be affected. The lB4

lg5

lQ8 lB7

lg8

Y. Lin, R. D. Kobes, I. L. Norton, and F. C. Hartman, Biochem. Biophys. Res. Comm., 1971,45,34; M. C. Paterson, I. L. Norton, and F. C. Hartman, Biochemistry, 1972,11, 2070. A. Meister, Adv. Enzymol., 1968, 31, 183.

Y. Tsuda, R. A. Stephani, and A. Meister, Biochemistry, 1971, 10, 3186. J. PatoEka, Coll. Czech. Chem. Comm., 1972, 37, 899. J. W. Hovanec and C. N. Lieske, Biochemistry, 1972, 11, 1051.

1 74 Organophosphorus Chemistry ageing of phosphonylated acetyl cholinesterase is due to cleavage of the P-0-aryl bond which should be very sensitive to substitution in the aryl ring. Both tris-(4-nitrophenyl) phosphate and bis-(4-nitrophenyl)carbonate react rapidly with the active site of a-chymotrypsin with the release of one equivalent of 4-nitrophen01.~~~ The resulting phosphorylated or acylated enzyme then releases a second equivalent of 4-nitrophenol in a reaction which involves the participation of a group on the enzyme with a pK, near 7, probably His-57. 9 Other Compounds of Biochemical Interest 2-(Dansy1amino)ethyl triphosphate (76) is a fluorescent substrate for heavy meromyosin-ATPase, behaving like ATP.200 Marked increases in the excitation and emission spectra of (76) on addition of heavy meromyosin are observed and the maximum of the emission spectra undergoes a slight

(76)

(77)

hypsochromic shift. This suggests that (76) is in a hydrophobic environment when bound to the enzyme. L-threo-Neopterin 2',3'-cyclic phosphate (77) has been isolated from Methylococcus capsulatus and its structure proved by degradative means.2o1 Like a similar dihydroneopterin cyclic phosphate which has been isolated from a strain of Comamonus,20athe pteridine moiety and the phosphate group are derived from the same GTP molecule. Further evidence on the structure of presqualene pyrophosphate (78) 203 has been put forward confirming earlier and the enzymic

(78) lgB 201

aoa

203 204

M. L. Bender and F. C. Wedler, J. Amer. Chem. Soc., 1972, 94, 2101. M. Onodera and K. Yagi, Biochim. Biophys. Acta, 1971, 253, 254. T. Urushibara, H. S. Forrest, D. S. Hoare, and R. N. Patel, Biochem. J., 1971,125,141. J. Cone and G. Guroff, J. Biol. Chem., 1971, 246, 979. J. G. Edmond, G. Popjhk, S. M. Wong, and V. P. Williams, J. Biol. Chem., 1971, 246,6254.

H. C. filling, C. D. Poulter, W. W. Epstein, and B. Larsen, J. Amer. Chem. SOC.,1971,

93, 1783; R. M. Coates and W. H. Robinson, ibid., p. 1785.

175

Phosphates and Phosphonates of Biochemical Interest

formation of squalene homologues from homologues of farnesyl pyrophosphate has been reported.20sThe inhibition of enzymic dephosphorylation of a C,,-isoprenyl pyrophosphate by the antibiotic bacitracin is abolished by the addition of chelating agents.2o* Various bivalent metal cations appear to participate in complex formation between the antibiotic and the isoprenyl pyrophosphate, and such metal complexes may be important in the mode of action of bacitracin on membranes. A new microbial metabolite, phosphoramidon (79),has been isolated from a strain of Streptomyces and its structure determined.207 The

CH-CH,CH( I NH I O=P-OH

Me

I

M 4 k O - r HO HO-f-+H OHHO

metabolite, which is hydrolysed by acid to leucyltryptophan, L-rhamnopyranose, and inorganic phosphate, is unusual in possessing a phosphoramidate bond. 205 ao6

207

K. Ogura, T. Koyama, and S. Seto, J . Amer. Chem. SOC.,1972, 94, 307. K. J. Stone and J. L. Strominger, Proc. Nut. Acad. Sci. U.S.A., 1971, 68, 3223. S. Umezawa, K. Tatsuta, 0. Izawa, and T. Tsuchiya, Tetrahedron Letters, 1972, 97.

8

Ylides and Related Compounds BY S. TRIPPETT

1 Methylenephosphoranes Preparation.-The preparation of methylenephosphoranes has been reviewed.l Pure methylenetriphenylphosphorane has been obtained as shown in Scheme 1, together with the pure trimethylsilylmethylene- and

bis(trimethylsilyl)methylene-phosphoranes.2 Ph3P: CH, 85%

+

Ph,PMe Br-

I

iii

I

Me4$ Br-J.

ii ----+

Me4; Br-J.

+ Ph,P: CH. SiMe, 77%, m.p. 12-13

Ph,P: C(SiMe,),

+ Ph,P: CH, 82%

iV

-+=

"C

&

49%,m.p. 139-140 "C

+

P$P. CH(SiMe,), Br-

1-

[ I

Reagents: i, NaH, THF; ii, Me3P:CH,, ether; iii, Me,P:CH.SiMe,, ether; iv, Me,SiBr; v, BuLi; vi, 270-300 "C, 0.1 mmHg

Scheme 1

Further examples have appeared of the use of epoxides as the source of the base in olefin synthesis, among them the synthesis of crocetin dialdehyde (1) shown in Scheme 2., Additional polymeric Wittig reagents have been described and used in olefin ~ynthesis.~ 1 3 4

H. J. Bestmann and R. Zimmermann, Fortschr. Chern. Forsch., 1971, 20, 1. H. Schmidbaur, H. Stuhler, and W. Vornberger, Chem. Ber., 1972, 105, 1085. G.P. 2 037 935-6 (Chem. Abs., 1971, 75, 20 707, 49 365). S. V. McKinley and J. W. Rakshys, jun., J . C . S. Chem. Comm., 1972, 134; W. Heitz and R. Michel, Angew. Chem. Internat. Edn., 1972, 11, 298.

176

177

Ylides and Related Compounds

I

(1) /

0

\

Reagents: i, MeCH,CH-CH,,

CH,Cl,, 75 "C Scheme 2

-

Phosphines and the imine (2) gave the stable ylides (3).5 R3P

+ PhCH: CH-N:C(CF3)Z

R3P:CPh- CH: N - CH(CF3), R = Ph or Pri (3)

(2)

The equilibrium established between methylenetriphenylphosphorane and ethyltriphenylphosphonium bromide in THF has been investigated by quenching with benzaldehyde. Ph3P:CH2

+ + Ph3PEt Br- 7 Ph3$Me Br- + Ph3P:CHMe 15:l

Reactions.-Halides. The stable ylides (4) are C-alkylated by p-nitrobenzyl bromide.' Methyl and ethyl iodides alkylate the formylstabilized ylides ( 5 ) exclusively on oxygen8 to give mixtures of cis- and trans-isomers not necessarily in ratios corresponding to the isomer compositions of the ylides. Dibromo- and di-iodo-methane gave the bisphosphonium salts (6). 2 Ph3P:CH-C 0 . R

+ p-NO,. C,H,. CH,Br

(4; R = OEt or Ac)

-

Ph3P:C(CO.R).CH,.C,H,.NO,-p

+ + Ph,P.CH,.CO*R Br-

Methylenetriphenylphosphorane with 1,Zdibromopropane gave the cyclobutylphosphonium salt (7), which was used in olefin synthesis. The @

K. Burger, J. Fehn, J. Albanbauer, and J. Friedl, Angew. Chem. Internat. Edn., 1972,11,

319.

A. Piskala, M. Zimmermann, G. Fouquet, and M. Schlosser, Coll. Czech. Chem. Comm., 1971,36,1482.

M. I. Shevchuk, A. F. Tolochko, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.),

1971, 41, 534. C. J. Devlin and B. J. Walker, Tetrahedron Letters, 1971, 4923. J. E. Baldwin and R. H. Fleming, J. Amer. Chem. Soc., 1972, 94,2140.

178

Organophosphorus Chemistry

stable a-chloro-ylides ( 8 ) were obtained as shown.lo

R’

‘OMe

PPh, 2 Ph,P:CH,

+

P h 3 k H , C O * R C1-

R

=

+

McCHBr.CH,Br

Br-

p-Me *C6H,.S0,.NHCI -+ Ph,P:CCI*CO*R

OMc, OEt, Me, or Ph

(8) > 70;/,

Carbonyls. The stable ylides (9) react with a-diketones to givell the 1,4-diketones (10). The allenic ketones (11) have been shown12 to be intermediates in the formation of 4-pyrans from diphenylketen and the ylides (9). The acridinium betaines (13) were formed l3 from the 2-aminonaphthoquinones (12) and arylidenephosphoranes under vigorous conditions, oxidation or disproportionation occurring at some stage. Wittig olefin syntheses in hydroxylic solvents may proceed via vinylphosphonium salts (14) and not via the usual oxaphosphetans when the double bond formed is stabilized by a n-bonding substituent.14 In some

(9) R1

10

11

12

lS

14

=

Me or Ph

H. J. Bestmann and R. Armsen, Synthesis, 1970, 590. E. Ritchie and W. C. Taylor, Austral. J. Chem., 1971, 24, 2137. M.Duprt and H. Strzelecka, Cumpt. rend., 1972, 274, C, 1091. H.J. Bestmann, H. J. Lang, and W. Distler, Angew. Chem. Internat. Edn., 1972, 11,59. E. E. Schweizer, D. M. Crouse, T. Minami, and A. T. Wehman, Chem. Cumm., 1971, 1000.

179

YIides and Related Compounds

(13) 11-46x

cases, e.g. (15), the vinylphosphonium salt may be isolated. However, the optically active benzylphosphonium salt (1 6) with benzaldehyde and ethanolic sodium ethoxide gives16 the oxide (17) with almost complete retention of configuration at phosphorus, and the vinylphosphonium salt Ph,P:CHR'

+

R2R3C0

Ph,;*CR': CR2R3 HO-

I

(14)

Ph,PO

+ +

ePh,6-CHR1.C(0)R2R3

-

Ph,6*CHR1.C(OH)R2R3 R40-

R'CH:CR2R3

Ph3P.CH2CH:CH2 +

M e E t P h k H , P h Br-

+

PhCHO

Br-

EtOH EIONa+

EtoH

+

PPh, Br-

o z k * C H : C H 2

Me Et PhPO

+

(17)

(16)

MeEtPh6CPh:CHPh (18)

l*

D. J. H. Smith and S. Trippett, J. C. 5'. Chem. Comm., 1972, 191.

PhCH:CHPh

180

Organophosphorus Chemistry

f

+

I

s3 t

(18) is therefore unlikely to be an intermediate unless it undergoes alkaline hydrolysis with complete retention of configuration at phosphorus. Vinylphosphonium salts have also been implicated in the complex reactions occurring when 2-hydroxyalkylphosphonium salts are treated with base in hydroxylic solvents,16 and l7 in the previously observed formation of the ethers (20) and (21) from the salt (19) and sodium methoxide. The stereospecificity of the /%oxido-ylide synthesis using formaldehyde as one of the aldehyde components is dependent on the order of use of the a1deh~des.l~Thus, starting from the ethylidenephosphorane, use of hexaldehyde and paraformaldehyde in that order gave almost pure isomer (22), while their use in the reverse order gave a mixture of the isomers (22) and (23) in the ratio 36 : 64. 16 '1

l9

J. W. Rakshys, jun., and S. V. McKinley, Chem. Comm., 1971, 1336. E. E. Schweizer, T. Minami, and D . M. Crouse, J , O r g . Chem., 1971, 36, 4028. E. E. Schweizer, C. J. Berninger, D. M. Crouse, R. A. Davis, and R. S. Logothetis, J. Org. Chem., 1969, 34, 207. M. Schlosser and D. Coffinet, Synthesis, 1971, 380.

181

Ylides and Related Compounds C5H11

Ph,P:CHMe

\

CH,OH

I

.'

The unexpected formation of ethyl a-safranate (26) from allylidenetriphenylphosphorane and the keto-ester (24) could involve coupling between the y-carbon of the ylide and the /I-carbon of the unsaturated ketone to give the betaine (25), followed by proton transfer and an intramolecular Ph,P:CH-CH:CH,

+

XC02EI 0

~

R 0 2 E t

f -

Ph,P+

(24)

(25)

Ph,P C0,Me

M~o-> M

e

0

R

Ii

1

(28) PIi,,P: Ct I M C

Meo C0,Me

R H

7

(29)

Organophosphorus Chemistry

182

Wittig reaction.20 Among other unusual olefin syntheses is the formation 21 of the six-membered olefin (29) from the five-membered ketone (27) and an excess of ethylidenephosphorane in DMSO. This probably involves initial base-catalysed isomerization of (27) to the six-membered ketone (28). A full account has appeared22of the use of ylides in the synthesis of cyclopropyl-substituted ethylenes. Among unsuccessful Wittig reactions noted is the failure of cyclohexylidenetriphenylphosphorane to give the olefin (30) on reaction with cycl~hexanone.~~

Ph,P :CCI,

+

PI1C0.CN

- PhC(CN):CCI, (31) 73;!

A full account has appeared 24 of the reactions of polyhalogenoacroleins, keto-acetals, ethyl pyruvate, and various halogenated unsaturated ketones with dichloro- and dibromo-methylenetriphenylphosphoranes generated in situ. This dichloro-ylide reacted 25 with the carbonyl of benzoyl cyanide in a normal olefin synthesis to give the unsaturated nitrile (31).

+ 0

Ph,P:CHR

R

0

(32)

R

=

21

23 24 26

I4

+

CO,E1 o r CN

(33)

2o

*OonC

---+

RR H H

R

(34)

G . Biichi and H. Wiiest, Helu. Chim. Acta, 1971, 54, 1767. E. G. Brain, F. Cassidy, A. W. Lake, P. J. Cox, and G . A. Sim, J. C. S. Chem. Comm., 1972,497. T . Teraji, I. Moritani, E. Tsuda, and S. Nishida, J . Chem. SOC.( C ) , 1971, 3252. J. B. Jones and P. W. Marr, Canad. J. Chem., 1970, 49, 1300. C. Raulet and E. Levas, Bull. SOC.chim. France, 1971, 2598. R. L. Soulen, D. B. Clifford, F. F. Crim, and J. A. Johnston, J. Org. Chem., 1971,36, 3386.

183

Ylides and Related Compounds

The bicyclic imide (32) reacted under vigorous conditions with stable ylides to give mixtures of the mono- and bis-olefins.26 The homologue (33) behaved similarly but no reaction was observed with (34). The sulphonamide (35) reacted normally 27 under vigorous conditions. Whereas the ester ylide (36; R = OEt) with N-p-nitrobenzoylaziridine gave the ylide (38) by proton transfer in the intermediate (37), the aroyl ylides (36; R = Ar') catalysed the conversion of the aziridine into the oxazoline (39), presumably uia the same type of intermediate.28 Ph,P:CHCO- R

+

ArCO-Nl

--+ Ph,kH(CO-R)CH,CH2NCO-Ar

(36)

Ph,P:C(CO, Et).CH,CH,N HCO-Ar

(38)

Ar

=

p-NO,.C,;H,

R

= At'

J.

Ph,P:CHCO.Ar'

+

Ar (39)

Among other carbonyl compounds successfully used in olefin synthesis are (40),29(41),30the optically active dione (42),31the pyrroles (43),32and the xanthone (44).33 In the last case the aldehyde was added rapidly to a large excess of the ylide, followed immediately by acetone to remove the excess reagent. Miscellaneous. The unusual reductions of benzyltriphenylphosphonium salts with sodium to give benzyldiphenylphosphine have been shown 34 to involve reduction of the benzylidenephosphorane. This ylide with sulphur in benzene at 70 "C gave 36 triphenylphosphine sulphide, a pentasulphide formulated as (45) or (46), and only traces of isomeric stilbenes. Previous workers 36 reported high yields of stilbenes from the same reaction carried out in refluxing toluene. Benzoylmethylenetriphenylphosphorane (47) with sulphur gave a polymer of the thioaldehyde (48). 2o 27 28 gs

30

32 33 34 35

36

W. Flitsch and B. Muter, Chem. Ber., 1971, 104, 2852. M. Natsume, M. Takahashi, K. Kiuchi, and H. Sugaya, Chem. and Pharm. Bull. (Japan), 1971, 19,2648. H. W. Heine and G. D. Wachob, J. Org. Chem., 1972, 37, 1049. N. N. Belyaev and M. D. Stadnichuk, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1888. L. D. Quin, J. W. Russell, jun., R. D. Prince, and H. E. Shook, jun., J. Org. Chem., 1971,36, 1495. D. A. Lightener and G. D. Christiansen, Tetrahedron Letters, 1972, 883. W. Flitsch and U. Neumann, Chem. Ber., 1971, 104, 2170. H. D. Locksley, A. J. Quillinan, and F. Scheinmann, J. Chem. SOC.( C ) , 1971, 3804. A. W. Herriott, Tetrahedron Letters, 1971, 2547. H. Tokunaga, K. Akiba, and N . Inamoto, Bull. Chem. SOC.Japan, 1972, 45, 506. H. Magerlein and G. Meyer, Chem. Ber., 1970, 103, 2995.

184

Organophosphorus Chemistry 0

R S i C H:C

H

a

("I

C HO

P

(40)

Me

O NC 0 - R ' H

+

Ph,P:CR'*CO,Et 0

(43)

4 6'X

(44)

Ph,P:CHPh

+

Ph,,PS

S8

83;;

+

/

PhCH

S

\

CIIPh

\

/

s.s.s.s

(45) 14:;

Ph,P:CHCO*Ph (47)

+

s8

+ Ph,,PS 4- (PhCO-CHS), (48)

185

Ylides and Related Compounds

Lithiation of the phosphorane (47) in benzene in the presence of HMPT gave 37 a solution containing the 'enolate ylide' (49), which on prolonged refluxing with ketones gave, after work-up, the ,€+unsaturated ketones (50). (47)

Li

Ph,P:C:C(OLi)Ph (49)

R'CH:CR2. CH2CO*Ph (50) 3 0 4 2 : ;

The phosphonium acetates (51) are soluble in organic solvents, in contrast to the previously prepared chlorides. With base in methanol they gave the bisphosphoranes (53), from which the divinylmercury compounds (52) were obtained on reaction with aldehydes.38 Ph,P:CHR'

+

Hg(OAc),

-

P h 3 k H R 1 * H g O A c AcO(51)

I

McOl1 hasc

K'CHO

R2CH:CR1*Hg*CR':CHR2 C-- Ph,P:CR'*Hg.CR':PPh, (52)

(53)

A full account has appeared3g of the reactions of acyl azides with P-keto-a1kylidenephosphoranes. These phosphoranes with ni trile oxides gave isoxazoles (54) 40* 41 and the stable ylides (56) or (57), formed as shown via the quinquecovalent 1 :1 adducts (55).41 The 3-pyrrolines (59) were formed on refluxing the aziridine (58) with the stable ylides Ph,P: CHR (R = CN or C0,Me) in toluene.42Methylenetriphenylphosphorane with benzoyl isocyanate gave a compound that has been assigned structure (60).43 ' 3

38 39 4O 41 42 43

C. Broquet and M. Simalty, Tetrahedron Letters, 1972, 933. N. A. Nesmeyanov, A. V. Kalinin, and 0. A. Reutov, Doklady Chem., 1970,195, 788. P. Ykman, G. L'AbbC, and G. Smets, Tetrahedron, 1971, 27, 5623. T. Sasaki, T. Yoshioka, and Y. Suzuki, Yuki Gosei Kagaku Kyokai Shi, 1970'28,1054 (Chem. Abs., 1971, 74, 125 528). G. L'Abbt, J.-M. Borsus, P. Ykman, and G. Smets, Chem. and Ind., 1971, 1491. F. Texier and R. CarriC, Tetrahedron Letters, 1971, 4163. Y. Ohshiro, Y. Mori, M. Komatsu, and T. Agawa, J. Org. Chem., 1971, 36, 2029.

186

Organophosphorus Chemistry

I

Ph3P:CHC0.R1

f

R 2 C N 0 --+

I

= PI1 -

PhCH-C(CO,Mc),

P 11

(58)

:5R’ N

~1

= M~

K’= PIl’

[

MeCOC:PPh,

MeCO -C: PPh:, I PhNHCO

---+

PhL:NOH]

I’1iJ1’0

PhCO.CH:C:NPh

\ N/

---+

(54)

R’COCH-PPh, / \ , R’C* o N

K’ = K‘

0 ;Ph, I I R’-C-CH I \ 0, ,,CR2 N

CHCO. I’ll

I’IlJ?

Ph,P:C(CO*Ph)-C(NHPh):CHCO.Fh (57)

+ K

Ph,P:CHR =

+

I cllu.;,

Ph,PCHR

-----+

toliicne

PhLH C(CO,Mc), \ /

CN or CO,Me

N Ph

OMe

I<

PI1,P:CR CO,Mc I I PhCH CHC0,Mc

4 -

\ /

N

Ph

Ph

(59) 70-90‘”

PhCO*NCO + Ph,P:CH,

, O

j

0 \\ CO*Ph C -N

Ph,P=C

/ \

,.”-E (60)

I

C=O

/

+

C,H,

187

Ylides and Related Compounds

The sulphonium chloride (61) reacted with a series of stable phosphoranes to form intermediates from which the sulphonium phosphoranes (63) were formed on hydrolysis and from which the methylthiophosphoranes (62) were obtained on heating.44 The meso-ionic dehydrodithizone (64) with the ester phosphorane gave a compound assigned 45 the betaine structure (65).

h 4 e 2 & b

CI-

R

0

=

+

Ph,P:CHR

__f

CO,Et, Ac, Bz, or CN H 2 0 , KI

(61) P h P :C R. SMe

Ph,P:CR.SMc,

(63)

(62) Ph

Ph

Ph

\

/

+

\

Ph,P:CHCO,Et

I-

--+

Y -N\

P11

/

s(64)

A further account has appeared 46 of the reactions of ylides with nitrosyl chloride, generated in situ from isopropyl nitrite and hydrogen chloride. The synthesis of phosphacyanines 47 has been extended 48 to include the use of vinyl ethers.

2 Phosphoranes of Special Interest Cyclic phosphonium ylides have been reviewed.4DAb initio calculations on methylenephosphorane, H2C:PH3, show no barrier to rotation round the CP bond whether or not d-orbitals are included in the c a l c ~ l a t i o n s .The ~~ energy changes when these orbitals are included are commensurate with p,.-d, feedback. Details have appeared 51 of the semi-empirical MO calculations on cyclopentadienylidenetriphenylphosphorane(66). A kinetic investigation of the reaction of this phosphorane with tetracyanoethylene in the presence 44

O5 46

47

48

49 50

51

E. Vilsmaier, W. Spruegel, and W. Boehm, Synthesis, 1971, 431. P. Rajagopalan and P. Penev, Chem. Comm., 1971, 490. M. I. Shevchuk, E. M. Volynskaya, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.), 1971, 41,2019. A. V. Kazymov, E. B. Sumskaya, K. M. Kirizlova, and E. P. Shchelkina,J. Gen. Chem. (U.S.S.R.), 1971, 41, 2459. H. Depoorter, J. Nys, and A. Van Dormael, Bull. SOC.chim. belges, 1964, 73, 939. M. Davies and A. N. Hughes, J . Heterocyclic Chem., 1972, 9, 1. I. Absar and J. R. Van Wazer, J . Amer. Chem. SOC.,1972, 94, 2382. K. Iwata, S. Yoneda, and Z . Yoshida, J. Amer. Chem. SOC.,1971, 93, 6745.

188

Organophosphorus Chemistry

of an excess of triethylamine52 has led to the establishment of an Elcb mechanism similar to that previously proposed for the reaction of (66) with tricyanovinylbenzene. A further account of the electrophilic substitution of (66) has appeared,53 the preferential substitution at position 2 of the cyclopentadiene ring being rationalized in terms of the greater stability of the Wheland intermediate. Dichlorocarbene also attacks (66) at the 2-position, leading to the aldehyde (67).54 CliO

(68)

(69)

Comparisons based on U.V. spectra, basicity, and reactions with aldehydes and with nitrosobenzene have been made among the betaines (68; R = Ph, X = P, As, Sb, Bi, S , Se, or Te) and the pyridinium betaine (69; R = H),56and among the betaines (68; R = H, X = P or As) and the betaine (69; R = H).56 The 3-phospholenium salt (70) with aromatic aldehydes and potassium t-butoxide in THF gave the trienes (71) in low yield,67presumably via the intermediate phosphine oxides (72). The unsaturated lactones (74) were

0 I L\

I-

+

2 ArCHO

-

Ar(CH:CH),Ar

Mc Me

0:P

/\

Me Me (72) 52

63 54 55 56

67

C. W. Rigby, E. Lord, M. P. Naan, and C. D. Hall, J. Chem. SOC.(B), 1971, 1192. D. Lloyd and M. I. C. Singer, Chem. and Ind., 1971, 786. Z. Yoshida, S. Yoneda, and T. Yato, Tetrahedron Letters, 1971, 2973. B. H. Freeman, D. Lloyd, and M. I. C. Singer, Tetrahedron, 1972, 28, 343. D. Lloyd and M . I. C. Singer, Tetrahedron, 1972, 28, 3 5 3 . D. Lednicer, J . Org. Chem., 1971, 36, 3473.

189

Ylides and Related Compounds

PhjP'

Br(73)

K

=

(74) 24

JJ-NO,-C,H,~,p-Me.C,H,, or Me

.?I",,

OM'

obtained 5 8 as single isomers of unknown geometry from the ylide (73) and aldehydes in refluxing dichloroniethane; (73) is stable for several days at - 15 "C. The phosphonium salt (75) with benzaldehyde and potassium t-butoxide gave the diene (77), as shown in Scheme 3.59 The base alone resulted in Ph,kH,C(:CH,)CO,Et

2 Ph,,kH:CMe.C(OH)Me2

Br-

5

Ph,P,

Br-

PhCH:CH.C(:CH,)C (OH)Mc,

(76) 80':::

(77)

Reagents: i, MeLi; ii, KOBut; iii, KOBut, PhCHO

Scheme 3

the formation of the stable quinquecovalent phosphorane (76), which did not react with benzal dehyde. Triphenylphosphine and diphenylcyclopr openone gave the stable keten-phosphorane (7QSo With methanol, (78) gave methyl a-phenylcinnamate and the phosphine, while a-phenylcinnamic acid led to the anhydride (Scheme 4). The iminocyclobutenone (79) was formed from (78) and 2,6-dimethylphenyl isocyanide. 2-Aminopyridine adds to the /3-acylvinylphosphonium salt (80) to give the salt (81a) or (81b), which has been used successfully in olefin synthesis.s1 The salts (82) with benzaldehyde and ethanolic ethoxide gave 62 the olefins (83), which were isolated when R1and R2 were phenyl, but otherwise gave the isomers (85) and/or the adduct (84) by reacting with a further molecule of aldehyde. 58 59 6o

62

J. E. T. Corrie, Tetrahedron Letters, 1971, 4873. C. F. Garbers, J. S. Malherbe, and D. F. Schneider, Tetrahedron Letters, 1972, 1421. A. Hamada and T. Takizawa, Tetrahedron Letters, 1972, 1849. E. Zbiral and E. Hugl, Tetrahedron Letters, 1972, 439. E. E. Schweizer and C. S. Khim, J. Org. Chem., 1971, 26,4033.

190

pl’yph +

Ph,P

0

(PhCH:CPh-CO),O

0rganophosphorus Chenzist ry

i Ph,P:CPh.CPh:C:O (78) 92‘:/,

J

+

Ph,P

1’11,

H

,C=C

, P 11

+

‘CO,Mc

Ph,P

Reagents: i, CBHB, R.T.; ii, PhCH:CPh*C02H;iii, MeOH

Scheme 4

(78)

+

c$tc hl e

Me

+

01’

Among other interesting phosphoranes used successfully in olefin synthesis are (86),63(87),64 (88; X = Br, OMe, OPh, SPh, or CN),65both geometrical isomers of (89),66(90),67(91),68and (92).69 63 64

65 OG

67 6n 69

B. P. 1250601 (Chem. Abs., 1972,74,4013). M. I. Shevchuk, M. V. Khalaturnik, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2172. M. Le Corre, Compt. rend., 1971, 273, C , 81. R. K. Howe, J . Amer. Chem. SOC.,1971, 93, 3457. M. B. Groen, H. Schadenberg, and H. Wynberg, J. Org. Chem., 1971,36,2797. S . Yoshina and I. Maeba, Chern. and Pharm Bull. (Japan), 1971, 19, 1465. S. Hunig and H.-C. Steinmetzer, Tetrahedron Letters, 1972, 643.

191

Ylides and Related Compounds

Ph

R'

(84)

Ylides have been implicated in the formation of acylcyclopropanes from the y-acyloxyphosphonium salts (93) as and in the very rapid reaction of the tributylphosphine-carbon disulphide adduct (94) with Ph,P:CHCH,NMe,

Ph,P :CR. CO-CO-Ar

(86)

(87)

c1 CH: PPh,

P h , P : C H a x CI

CH: PPh,

7o

E. E. Schweizer and W. S. Creasy, J . Org. Chein., 1971, 36, 2379.

I92

Organophosphorus Chemistry t

Ph3PCH2CH2CR1R2 .0C0.R3 Br-

R3C&Rl

l3LlfOH>

II

(93)

+

Ph3P0

R2 42-59';;:

? I

I

I

I

II

I

0

,

I

+

Bu,PCS,-

+

RCER

+

ArCHO +

Kx l ) = C F I A r

+

Bu,PO

R

(94)

(95)

(96)

electrophilic acetylenes and aromatic aldehydes to give the benzylidene1,3-dithioles (95).71 The speed of the latter reaction was ascribed to the anti-aromatic nature of the postulated intermediate ylide (96), if planar. 3 Selected Applications of Ylides in Synthesis Natural Products.-A number of 'one-step' olefin syntheses have appeared in which phosphine, alkyl halide, and carbonyl compound are allowed to react together in the presence of a suitable epoxide as the source of base. Among them are the synthesis of ( &)-mitorubrin 7 2 and of the polyene (97) (Scheme 5).73 Sirenin (98) has been obtained via an electrocyclic reaction of a cis-divinylcyclopropaneas shown in Scheme 6.74 The trans-olefin synthesis 71 72

73 74

H. D. Hartzler, J. Amer. Chem. Soc., 1971, 93, 4961. R. Chong, R. W. Gray, R. R. King, and W. B Whalley, J. Chenz. SOC. ( C ) , 1971, 3571. G.P. 2 132 032 (Chem. Abs., 1972, 76, 99 874). L. Jaenicke, T. Akintobi, and D. G. Muller, Angew. Chem. Internat. Edn., 1971, 10, 492; A. Ah, D. Sarantakis, and B. Weinstein, Chem. Comm., 1971, 940.

193

Ylides and Related Compounds

+

/

CICH,CMe:CH.CO,Et

Ji

+

Ph:,P

0

\

Reagents: i, MeCH,CH-CH,,

90 "C, 24 h

Scheme 5

6:;"

H * C C - Et

,

11

CHZCH,

+

. CH:CH,

Ph,P:CH*CiC.Et I

6

1

1

J

1

ci C.Et

i, i

li

\

I

(98) Reagents: i, PhJ':CH.CH:CHEt; ii, H2, Lindlar catalyst Scheme 6

i, PhLi ii, MeOlT

194

Organophosphorus Chemistry

of Schlosser, involving stereospecific protonation of a /3-oxido-ylide, has been applied 7 5 to the preparation of a sample of ( k )-progesterone precursor (99) containing only 3% of the cis-isomer. Full details have appeared 76 of the synthesis of chlorobiumquinone, and the 1,Sdiene synthesis 77 involving coupling of allylidenephosphoranes with allylic bromides has been applied to the synthesis of squalene. The dione (100) reacted exclusively at the exocyclic carbonyl in a synthesis 7 9 of methyl 9 4 s - (101) and 9-trans-trisporates B. Although (+)-dihydro-/3-santalol (103) was obtained from (102) in 90% yield if the hydroxy-group was protected as the borate ester, use of unprotected (102) gave predominantly the isomeric olefin (104)?O Similarly the hydroxyketone (105) gave the olefin (106), but similar rearrangements did not occur using the isopropylidene- or ethoxycarbonylmethylene-phosphoranes. 0

( 103)

‘OH

. l .

‘OH

( 103)

( 104) i5

76

77

78

79

W. S . Johnson, M. B. Gravestock, and B. E. McCarry, J . Amer. Chem. SOC.,1971, 93, 4332. C. D. Snyder, W. E. Bondinell, and H. Rapoport, J. Org. Chem., 1971, 36, 3951. E. H. Axelrod, G. M. Milne, and E. E. van Tamelen, J . Amer. Chern. SOC.,1970, 92, 2139. U. T. Bhalerao and H. Rapoport, J. Amer. Chem. Suc., 1971, 93, 5311. S. Isoe, Y. Hayase, and T. Sakan, Tetrahedron Letters, 1971, 3691. W. I. Fanta and W. F. Erman, J. Org. Chem., 1972, 37, 1624.

Ylides and Related Compounds

n

n

195

Among many other syntheses involving extensive use of ylides are those of lycoxanthin,81 P,y- and y,y-carotene,82 10,ll:lo’, 1 1’-bisdehydrorhodoan thin,^, ethyl ( - )-ab~cisate,~~ p r ~ p y l u r eand , ~ ~ of juvenile hormone.86 In the course of the last mentioned, the phosphonium salts (107; X = H or SiMe,) were used successfully in olefin synthesis, but reactions involving the salt (107; X = CH,OH) were not successful. Among hindered ketones reported to give poor yields on methylenation are (108) and (109).s8

+

PhBPCH,CH,CH,Ci C X I‘ ( 107)

[2-3H]Lachnophyllummethyl ester has been obtained using the phosphorane Ph3P: C3H*C02Me,while the phosphorane Ph,P: 14CH-C02Me has been used in the synthesis of 14C-labelledabscisic acid. Macrocyclic Compounds.-Further information has appeared 91 on the oxidation of bifunctional y1ides:with oxygen to give macrocyclic polyolefins. The bisphosphorane (1 10) with the dialdehyde (1 11) gave the cycloheptatriene (112), from which the cation (113) was obtained on treatment with 82

84 86 8*

87 88

88

H. K j ~ s e nand S. Liaaen-Jensen, Acta Chem. Scand., 1971, 25, 1500. A. G. Andrewes and S. Liaaen-Jensen, Acta Chem. Scand., 1971, 25, 1922. U.S.P. 3 624 105 (Chem. Abs., 1972,76, 72 678). T. Oritani and K. Yamashita, Tetrahedron Letters, 1972, 2521. A. I. Meyers and E. W. Collington, Tetrahedron, 1971, 27, 5979. J. S. Cochrane and J. R. Hanson, J. C. S.Perkin I, 1972, 361. E. Piers, W. de Waal, and R. W. Britton, J . Amer. Chem. SOC.,1971, 93, 5113. A. Deljac, W. D. MacKay, C. S. J. Pan, K. J. Wiesner, and K . Wiesner, Canad.J. Chem., 1972, 50, 726. F. Bohlmann and T. Burkhardt, Chem. Ber., 1972,105, 521; G. C. Barley, A. C. Day, U. Graf, E. R. H. Jones, I. O’Neill, R. Tachikawa, V. Thaller, and R. A. Vere Hodge, J . Chem. SOC.,(C), 1971, 3308. J. C. Bonnafous and M. Mousseron-Canet, Bull. SOC. chim. France, 1971, 4551. H. J. Bestmann and H. Pfuller, Angew. Chem. Internat. Edn., 1972, 11, 508.

196

Organophosphorus Chemistry

(1 12)

( 1 13)

trityl f l u o r ~ b o r a t e .Among ~~ other cyclic polyolefins prepared by Wittig olefin syntheses are the [20]annulene (1 14),93 the dianthr[ 14lannulene (1 15),94 and (1 16) 95 (of unknown geometry). ~~ In the first assignment of absolute configuration to a h e l i ~ e n e ,the bisphosphonium periodate (1 18), obtained from the binaphthyl (1 17) of known absolute configuration, reacted with base to give ( +)-(P)-pentahelicene (1 19). Wittig reactions have also been used to obtain the stilbenes required for photochemical cyclization to give [8]heli~ene,~~ and a [Glhelicene of known absolute config~ration.~~

+

( 1 14)

92

93 94 95 86

g7 s8

P. J. Garrett and K. P. C. Vollhardt, Chem. Comm., 1971, 1143. H. Saikachi, H. Ogawa, and K. Sato, Chem. and Pharm. Bull. (Japan), 1971, 19, 97. S . Akiyama and M. Wakagawa, Bull. Chem. SOC.Japan, 1971, 44, 3158. C. D. Tulloch and W. Kemp, Chem. Comm., 1971, 747. H. J. Bestmann and W. Both, Angew. Chem. Internat.Edn., 1972, 11, 296. R. H. Martin and J. P. Cosyn, Synthetic Comm., 1971, 1, 257. J. Tribout, R. H. Martin, M. Doyle, and H. Wynberg, Tetrahedron Letters, 1972,2839.

197

Ylides and Related Compounds 2Br-

P h3P CH,

+

CH2PPh3

+

+-

PhLi

(115) 21%

xcH2fph3 CH2PPh3

+

0

OHC \

CHO

(116) 127;

I

-50 "C LiOEt

198

Organophosphorus Chemistry

The bridged hetero[l llannulenes (120) have been obtained as Evidence from their n.m.r. spectra suggests that they exist in the syn-form (121). The bright red thienocyclobutadiene (122) was obtained looas shown. Among other heteroannulenes synthesized using Wittig olefin syntheses are a thia[l l]annulene,lol an 0xa[l3]annulene,~~~ the oxat1 Slannulene

Ph,6CH2

QCHO - CHO

+

/

X 2BrPh3PCH2 + /

LiOMe

DMFI

x x

P 11

s -

- 7 8 C

/

P ti

t

Ph, I’C H., \ X 2Br-

+ /

P t i .,I’ C H

s, zo::,

0, 2”/,

I:: P I1

Pli,,P: C H \

= =

Ph (122) 3.59,’,

LiOEt, DMF 90 ‘ C

0

x X

= =

/

0, 15.3O,, CH,, 11.2”{, ( 1 23)

E. Vogel, R. Feldmann, H. Duwel, H.-D. Cremer, and H. Gunther, Angew. Chem. Internat. Edn., 1972, 11, 217. l o o P. J. Garratt and K. P. C. Vollhardt, J. Amer. Chem. SOC.,1972, 94, 1022. lol A. B. Holmes and F. Sondheimer, Chem. Comm., 1971, 1434. lo2 A. P. Bindra, J. A. Elix, and M. V. Sargent, Austral. J. Chem., 1971, 24, 1721. 99

YIides and Related Compounds

199

(123 ;X = 0)which is antiaromatic,lo3and thia-[17]- and -[21]-annulenes.lo4 With trityl fluoroborate, (123; X = CH,) gave the aromatic cation (124). The 1,6-dithia[lO]annulene (1 26) lo5 shows no paramagnetic ring-current and is probably non-planar. The synthesis failed with the salt (1 25 ;X = 0).

(126) 4 -6;;

Carbohydrates.-The synthesis of branched-chain sugars containing the gem-hydroxyformyl group has been achieved lo6by the sequence: \

,C:O

+

Ph,P:CHCN

H+

---+

\

,C:CHCN

KMnO,

-.. / * I 4 /C'CHO

The formyl group is attached to the more hindered face of the ring. Among other phosphoranes used in olefin syntheses with protected aldehydo- or keto-sugars are Ph,P: CH-SMe,lo7Ph3P: CH-C02R,lo8and Ph,P: CH*P(:O)(OPh)2.10g 4 Selected Applications of Phosphonate Carbanions Although the magnesium salt (127; M = 4Mg) could be alkylated and acylated on carbon, the potassium salt (127; M = K) in ether-dioxan with chlorotrimethylsilane gave acetonitrile and the phosphate (1 28) as the only identifiable products from a reaction which may involve silylation of the ambident phosphonate carbanion on oxygen.11o Allylic phosphonate

H. Ogawa, M. Kubo, and H. Saikachi, Tetrahedron Letters, 1971, 4859. T. M. Cresp and M. V. Sargent, Chem. Comm.,1971, 1458. l o 6 P. J. Garratt, A. B. Holmes, F. Sondheimer and K. P. C. Vollhardt, Chem. Comm., 1971,947. l o 6 J. M. J. Tronchet, R. Graf, and R. Gurny, Helu. Chim. Acta, 1972, 55, 613. lo' J. M. J. Tronchet and R. Graf, Helu. Chim. Acta, 1972, 55, 1141. l o 8 Yu. A. Zhdanov and L. A. Uzlova, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1401. loS H. Paulsen, W. Bartsch, and J. Thiem, Chem. Ber., 1971, 104, 2545. M. Kirilov and G. Petrov, Chem. Ber., 1971, 104, 3073. lo3 lo4

200

Organophosphorus Chemistry

+ p-O,N -C,H,.CHO

Me,CHCH: C(CN)P(:O)P(OEt), ( 1 29)

NnH

+

PhCMe:C(CN)P(:O)(OEt), ( 130)

I

PhC€IO NaH

PhCH:CH.CPh :C(CN)P(:O)(OEt), 52"o

carbanions react with aldehydes, attack being at either the a- or the y-carbon, depending upon the substituents.lll Thus the anion from (129) reacted entirely at the a-position whereas that from (130) was attacked at the y-position. The phosphonate (1 3 1) with benzaldehyde and sodium hydrogen carbonate gave ll1 the olefins (1 32) and the isomeric phosphates (1 34), formed via the intermediates (1 33). PhCH(CN)*CH(CN)P(:O)(OEt),

+

I

PhCHO ROH NaHCO,,

PhCH(CN)-C(CN):CHPh (132)

+

Ph C H 0P (:0)(0Et )

I

,

PhC(CN)CH,CN

7

( 1 34)

PhCH-6) QWOEt), PhC -CH I I C N CN

I

( 133)

Whether a Michael or a Horner reaction occurs when an @-unsaturated ketone is treated with a phosphonate carbanion depends upon the conditions.l12 Chalcone and the ester phosphonate (135) gave the product of a Horner reaction with sodium hydride in diglyme, but Michael addition occurred with sodamide in ether. The formation of deoxybenzoin on hydrolysis of the product obtained from benzonitrile and the benzylic phosphonate carbanion has been ll1 D. Danion and R. CarriC, Tetrahedron Letters, 1971, 3219. 112

E. D. Bergmann and A. Solomonovici, Tetrahedron, 1971, 27, 2675.

Ylides and Related Compounds

201 PhCH:CH-CPh: CH.CO,Et 52:,;

PhCH:CH.CO.Ph

+

(Et0)2P(:O)CH2C02Et

,

.

( E t 0) P( :0)C H(C0, E t ) C H Ph C H,CO *Ph

42%

rationalized as shown in Scheme 7.113 The ratio of the isomeric unsaturated nitriles (136) and (137) obtained from the nitrile phosphorane and 3,3-dimethylcyclohexanone varies from 28 : 72, using methyl-lithium in benzene, to 60 : 40 when one uses sodium hydride in D M F or DMS0.114

PhCN

+

0 II (Eto), P-

(EtO),P(:O)CHPh

--+

4

72%

I

N=CPh

0 (Et0)Zi /I

PhCH,CO.Ph

CH Ph

iHPh

1120

N-APh

Scheme 7

The same phosphonate with the anhydride (1 38) gave 115 the phosphonate (1 39 ;X = CN), existing as the acid (1 39) in the solid and as an equilibrium between (1 39) and the lactone (140) in solution. The corresponding product from the ester phosphonate is the lactone (140; X = C02Et) both in the solid and in solution. 113

F. Mathey and J.-P.Lampin, Tetrahedron Letters, 1972, 1949.

J. H. Babler and T. R. Mortell, Tetrahedron Letters, 1972, 669. n5 C. Gadreau and A. Foucaud, Compt. rend., 1972, 274, C, 810. 114

202

i“ Ph .C -C H, 7 \ ,C, ,C’ 0’ 0 I

X ‘P(OEt), I1

o,H...o

Among interesting olefin syntheses with ester phosphonates are those with the allenic aldehydes (141) 116 and with the steroidal epoxy-aldehyde (142).l17 The yield of allenic carboxylic esters has been increased118 to RC H :C :C H .C H 0 (141) R

=

+

Pr’ or CSH,,

(M eO), P ( :0)C H,C 0 2 Me (MeOCH,), 60 ‘ c

RCH: C:CH- CH:CH.CO,Me CHO

(EtO),P(:O)CH,CO,Me C H: CH - CO, hlc

92%

70430% by carrying out the reactions between ketens and ester phosphonate at 115 “C. The phosphonate (MeO),P(: 0)14CH,C0,Me has been used in a synthesis of labelled juvenile horrnone.ll9 116

11’

11*

ll9

P. D. Landor, S. R. Landor, and S. Mukasa, Chem. Comm.,1971, 1638. U. Stache, K. Radscheit, W. Fritsch, W. Haede, H. Kohl, and H. Ruschig, Annalen, 1971,750, 149. G. Kresze, W. Runge, and E. Ruch, Annalen, 1972,756, 112. W. Hafferl, R. Zurflueh, and L. Dunham, J. Labelled Compounds, 1971,7, 331.

Ylides and Related Compounds

203

5 Ylide Aspects of Iminophosphoranes The bis(iminophosph0ranes) (143) and (144) have been obtained as shown.120 Electrophilic olefins and the phosphino-imines (145) gave 121 the cyclic iminophosphoranes (146). CCI, + + R',P(CH,),,PR',

+

-

R2NH2

R2NH.PR',. (CH2);PR',*NHR2

2CI-

1

K N Hz,

R2N:PR1,.(CH2),-PR12:NR2 ( 143)

R3P

+

CCI,

H,N(CH2'),NH2 -+

+

+

R,PNH(CH2),NHPR,

2CI-

KNH,

R,P: N(CH,),N:PR, ( 144)

R1,PN :CR2,

+

CH,:CHR3 = >

R12PQR12

( 1 45)

R3 (146)

Additional examples have been obtained122 of the change in the rate-determining step, from betaine formation to betaine decomposition, in the reactions of aromatic aldehydes with the iminophosphoranes R22$(N:PR13)2 RZ2,PF6,- + Me3SiF

(148)

R1,P:NSiMe3

R1 = Me, Pr', or Ph (14')

kF4 R2P(N:PR1,),

R2PF,-

+

Me,SiF

( 149) R. Appel, B. Blaser, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 1971, 104, 1847. 121 A. Schmidpeter and W. Zeiss, Angew. Chem. Internat. Edn., 1971, 10, 396. l Z 2 S . C. K. Wong and A. W. Johnson, J. Org. Chem., 1972, 37, 1850.

120

204 Organophosphorus Chemistry Ph,P: N - C6H4-X as X changes from electron-withdrawing to electronsupplying. d,-p, Bonding between phosphorus and nitrogen in the phosphorane Ph3P:NSO2*CGH4* Me-p is suggested 123 on the basis of its crystal structure. The trimethylsilyliminophosphoranes (147) with tri- and tetra-fluorophosphoranes give the salts (148) and (149), respe~tive1y.l~~ lZ3

lZ4

A. F. Cameron, N. J. Hair, and D. G. Morris, Chem. Comm., 1971, 918. W. Stadelmann, 0. Stelzer, and R. Schmutzler, Z. anorg. Chem., 1971, 385, 142.

9

Phosphazenes BY R. KEAT

1 Introduction Activity in this area continues at about the same level as last year, although an increasing emphasis on the physical properties of the phosphazenes is apparent. On the chemical side, several novel routes to both acyclic and cyclic phosphazenes have been developed, and the aminocyclophosphazenes remain a major source of interest. 2 Synthesis of Acyclic Phosphazenes From Amides and Phosphorus(v) Halides.-Aminodifluorophosphine, FZP*NH2, which was only recently reported, has been shown to undergo the Kirsanov reaction, giving an N-phosphinophosphazene, of which there are few examples known :

A surprising feature of the 31Pn.m.r. spectrum of this derivative was the apparent absence of P-N-P spin-spin coupling, since previous derivatives of this type have been characterized by relatively large coupling constants (ca. 100 Hz). A new and convenient route to the N-phosphinylphosphazene, ClZP(0)~N=PC13, has been

The reaction is general for ammonium salts, but for optimum yields ammonium sulphate is preferred. Further details of the stepwise synthesis of linear oligomeric phosphazenes have appeared.* The introduction of each phosphazene unit is accomplished by reaction of a P-chlorophosphazene with hexamethyldisilazane, (Me,Si),NH, and, subsequently, phosphorus pentachloride. The reactions with N-phosphinothioylphosphazenes are thus : a

*

G. E. Graves, D. W. McKennon, and M. Lustig, Inorg. Chem., 1971, 10, 2083. J. Emsley, J. Moore, and P. B. Udy, J. Chern. Soc. (A), 1971, 2863. J. Emsley and P. B. Udy, G.P. 2 117 055 (Chem. Abs., 1972,76, 101 801). H. W. Roesky, L. F. Grimm, and E. Niecke, Z. anorg. Chem., 1971,385, 102.

205

206 X1X2P(S)-N=PCI,

+ (Me,Si),NH

-

Organophosphorus Chemistry X1X2P(S)-N=PCI,. N H . SiMe,

lgF and 31P n.m.r. spectroscopy showed that pure isomers are difficult to obtain in all cases because of a tendency for exchange of fluorine and chlorine atoms to occur. An analogous P-trifluorophosphazenyl derivative was obtained by a more conventional route:

The linear triphosphazene C12P(S)(N=PCl,)3Cl has also been obtained by the disilazane-phosphorus pentachloride route, and this reacts with a further mole of hexamethyldisilazane to give the precursor of a tetraphosphazene, Cl,P(S)(N=PCl,),NH- SiMe,. The product from the reaction of heptamethyldisilazane and the diphosphazene Cl,P(S)(N=PCl,),Cl eliminates trimethylsilyl chloride on heating to 100 "C to give the novel cyclodiphosphazene (1). Details of the 31P n.m.r. spectra of the foregoing phosphazenes were given. CI,P(S)(N=PCI,),NMe.SiMe,

I1

>-

N,

PCI, I P

,NMe

s4\ c1 (1)

CH,CI I

CH,CI I

The possibility of obtaining compounds with useful physiological activity still prompts investigations into the properties of phosphazenyltriazines such as (3), which was characterized as its trianilino- and triphenoxy-derivatives. Full experimental details of the reaction of sulphamic acid with phosphorus pentachloride to give the phosphazenyl H. W. Roesky, Chem. Ber., 1972, 105, 1439. L. A. Lazukina, N. G . Kotlyar, V. P. Kukhar', and S. N. Solodushenkov, J . Cen. Chetti. (U.S.S.R.), 1971, 41, 2413.

207

Phosphazenes

derivative, Cl,P=N- SO,CI, have a p p e a ~ e d , ~as~well as further information on the nature of the products of the Kirsanov reactions of carboxylic amides with phosphorus pentachl~ride.~~ lo

From Cyano-compounds and Phosphorus(v) Halides.-The products from the reactions of acetonitrile and chloroacetonitriles with phosphorus pentachloride have been re-examined.ll The formation of compounds of structure (4) from the reaction with acetonitriles is confirmed, as well as the intermediates (9,but there was no evidence for the existence of cisand trans-isomers of (4) or ( 5 ) (X = H) as previously postulated. The

(4)

x,,c=c, ,N=PCI,

CI

P(O)CI,

X

=

so,

+-

(5)

(4)

H,S

s, ,N=PC13 ,c=c, c1 P(S)Cl, X

H or C1

=

H or C1 (7)

(6)

reactions of the compounds (4) with sulphur dioxide and with hydrogen sulphide have been shown to give phosphinyl- (6) and phosphinothioyl- (7) olefins, respectively. In the same way, dichloroacetonitrile and phenyltetrachlorophosphorane give an N-chloroalkylphosphazene in which the olefinic linkage can be readily chlorinated : CHC12CN

+ PhPCI,

CI,C=CCl.N=PPhCl,

c C1,C. CCl, * N=PPhCl,

However, nitriles of the type RCH2CN (R = alkyl or aryl) give resinous products with phenyltetrachlorophosphorane,12 possibly because the T. Moeller, T.-H. Chang, A. Ouchi, A. Vandi, and A. Failli, Inorg. Synth., 1972, 13, 9. 1971, 6, 93. V. P. Rudavskii, D. M. Zagnibida, and V. I. Konchatenko, Farm. Zhur. (Kieu), 1971, 26, 14 (Chern. Abs., 1972, 76, 3496). G. I. Derkach, E. S. Gubnitskaya, and V. A. Shokol, Ref. Zhur. Khim., 1970, Abs. No. lOZh 528 (Chem. Abs., 1971,75, 76 053). E. Fluck and W. Steck, 2. anorg. Chem., 1972, 387, 349. N. D. Bodnarchuk, V. Ya. Semenii, V. P. Kukhar’, and A. V. Kirsanov, J . Cen. Chem. (U.S.S.R.), 1971, 41, 989.

* T. Moeller and R. L. Dieck, Prep. Inorg. Reactions, lo

l1 l2

208

Organophosphorus Chemistry

unsaturated compounds formed initially are chlorinated by the phosphorane. These difficulties have been overcome by simultaneous reaction of these nitriles with dichlorophenylphosphine and chlorine : RCH,CN

+ PhPCI, + Cl,

RCCI,CCI,.N=PPhCI,

-

These compounds were converted to imino-derivatives on reaction with arenesulphonamides : RCCI,CC12.N=PPhCI,

+ ArSO,NH,

ArSO,N= C(CCI,R)N=PPhCI,

Malononitriles undergo interesting reactions with phosphorus pentach10ride.l~ For example (8) is cyclized to a monophosphazene (9) in refluxing chlorobenzene solution and may be re-formed by addition of

A'r

(8)

Ar

=

various methyl-, chloro-, or nitro-substituted phenyl groups

(9)

water to (9) under mild conditions. In addition, the reactions of (9) with formic acid give the hydroxy-phosphazenes (1 0) and P-phenoxy-derivatives of (9) can be obtained by treatment with sodium phenoxide. Alkyl derivatives of (9) have been obtained l4 by the same route and show similar reactivity to nucleophiles. They also form molecular complexes with two molecules of phosphorus pentachloride, but the structure of these complexes is not known. The aryl tricyanides ArHC(CN)CH(CN), undergo a cyclization reaction with phosphorus pentachloride l5 to give the azoles (1 1). This contrasts l3 l4

l6

P. P. Kornuta, A. I. Kalenskaya, and V. I. Shevchenko, J . Gen. Chem. (U.S.S.R.), 1971, 41, 993. P. P. Kornuta, A. I. Kalenskaya, and V. I. Shevchenko, J . Gen. Chem. (U.S.S.R.), 1971, 41, 2416. V. I. Shevchenko and N. R. Litovchenko, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1252.

209

Phosphazenes

with the results obtained last year for analogous alkyl tricyanides, which gave phosphazenes with acyclic N-substituents. Compounds of the type (1 1) undergo reactions typical of trichlorophosphazenyl derivatives, including the conversion of the -N=PC13 group into the -NHP(O)Cl, ArCH(CN)CH(CN),

pclj

Ar-C=C-CN I I CI-C, ,C-N=PCI,

N

\ c1

(1 1)

group by reaction with formic acid. Aroylcyanamides have also been shown l6 to produce monophosphazenes on reaction with phosphorus pentachloride : ArCONHCN

PC16

>

ArCO.N=CCI.N=PCl,

It is probable that these derivatives are formed via the imide ArCO-NH. CC1=N-PCl4, because imides of the type Alk2N*CCl=N-PCl, are obtained from the reactions of dialkylcyanamides with phosphorus pentachlori de. Details have been given l7 of the reaction of tetramethylene dicyanide with phosphorus pentachloride, which produces the expected diphosphazene (CH2),(CC1,CCl2 N=PCl,),.

-

From Azides and Phosphorus(II1) Compounds.-The reactions of azides with phosphorus(II1) compounds continue to be an important general route to monophosphazenes : R1N3

+ R2,P

-

R1N=PR2,

+ N2

New variations on this theme have been included in the synthesis of large numbers of N-alkylcarbamates, AlkO- CO. N=PR3 (R included alkyl,18 dialkylaminoJ8, and alkoxy-groups 19). Phosphazenes of structure (12) with N-phenolic (Xl = OH; X2 = ha1 or NO,)20 and N-aminophenyl

10

17 18

19 20

I. M. Kosinskaya, A. M. Pinchuk, and V. I. Shevchenko, J. Gen. Chem. (U.S.S.R.), 1971,41, 2422. V. I. Shevchenko and V. P. Kukhar’, Ref. Zhur. Khim., 1970, Abs. No. lOZh532 (Chem. A h . , 1971,75, 76 046). V. A. Shokol, L. I. Molyavko, N. K. Mikhailyuchenko, and G . I. Derkach, J. Gem Chem. (U.S.S.R.), 1971, 41, 312. V. A. Shokol, L. I. Molyavko, and G . I. Derkach, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2405. I. N. Zhmurova, A. P. Martynyuk, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 787.

210

Organophosphorus Chemistry

(Xl = NH,; X2 = H, hal, or alkyl),l substituents have been similarly obtained, and the basicities of the amino-phenols have been shown to be less than those of the corresponding triphenylphosphazenyl-phenols.20 Monophosphazenes, Ph3P=N. C6H4-p-N=NoC6H4-p-X (X = H, hal, NO,, OH, Me, OMe, NMe,, or N=PPh3) continue to attract attention22 because of the auxochromic action of the triphenylphosphazenyl group, -N= PPh3, which influences colour changes similar to those affected by the dimethylamino-group. N-Phosphinyl phosphazenes, MeP(0)(R1). N=PR2,, have been prepared from the phosphinyl azides Me(R1)P(0)N, and phosphines PR23(R1 included C1, NEt2, NHPh, NH.CO.OAlk, NH- C O . OPh, NH. CO-NHPh, and N=PPh3; R2 included Ph, NEt2, OEt, and OPr').,, N-Trimethylsilylphosphazenesare useful for the characterization 24 of silyl azides, e.g. R1R2Si(N3)2

PPhs

R1R2Si(N=PPh,), (R1 = R2 = Me or Ph; R1 = Me, R2 = Ph)

The crystalline intermediates expected in the reactions of benzoyl azide = 0) and phenylazido formate (n = 1) with tris(dialky1amino)phosphines have been characterized 25 and shown to eliminate nitrogen at 40-90 "C:

(n

R,P

+ N3*CO*(0),Ph

R,P=N*N=N.CO*(O),Ph

-

R,P=N CO * (O),Ph (R = Et,N, piperidino, or morpholino)

The use of monophosphazenes of the type Bu,P=N*C,H,X (X = o-NO,, m-F, m-CF,, or o-CF,), prepared by the azide route, for plant growth retardation has been proposed in a patent application.26 Other Methods.-In an extension of a recently developed synthesis of phosphazenes it has been shown2' that tertiary phosphines react with carbon tetrachloride and methylene diamines to give diaminophosphonium salts: R1,R2P

+ CCI, + H,N(CH2),NH2

-

[R12R2PNH(CH2) ,,NHPR1,R2I2+2 C121

I. N. Zhmurova, A. A. Tukhar', and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1971,

22

I. N. Zhmurova, R. I. Yurchenko, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.),

23

V. A. Shokol, G. A. Golik, and G. I. Derkach, J. Gen. Chenz. (U.S.S.R.), 1971, 41,

24 25 2*

41, 791.

1971, 41, 783.

539. S. S. Washburne and W. R. Peterson, J. Organometallic Chem.. 1971, 33, 153. K. Pilgram, F. Gorgen, and G. Pollard, J . Heterocyclic Chem., 1971, 8, 951. S. J. Kuhn, U.S.P. 3 557 208 (Chem, A h . , 1971, 75, 6096). R. Appel, €3. Blaser, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 1971, 104, 1847.

Phosphazenes 21 1 These salts may be deprotonated by ammonia to give the correspond[n = 0, 2, or 3, ing diphosphazenes, R1,R2P=N(CH,),N=PR1,R2 R1 = R2 = Ph; n = 2, R1 = Ph, R2 = Me,S(O)=N-1, and the dimethylene derivative readily gave a diquaternary salt with methyl iodide. In analogous reactions with tris(dimethylamino)phosphine, deprotonation of the diaminophosphonium salt was best effected by potassamide, leaving the strongly basic diphosphazene (Me,N),P=N(CH,),N=P(NMe,),. This route to phosphazenes was also successful 28 in reactions with sulphonamides :

+

+

EtsN

+ Ph2R1P=N*SOzNR2, Ph,PR1 CCI, H,N.S0,NR2, [R1 included Ph and Me,S(O)=N; R2 included H and Me]

With bis(diphenylphosphin0)-ethane and -propane, diphosphazenes RS02N=PPh2(CH,),,,PPh2=N* SOzR (R included NMe,, Ph, and C,H,-p-Me) were formed, but only a monophosphazene was obtained from bis(dipheny1phosphino)methane : (Ph,P),CH,

+ H,N*SO,R

EtaN CClr

Ph,P. CH,. Ph2P=N*S02R

(R = NMe, or Ph) In a related series of reactions,29 monophosphazenes were prepared from phosphorus(II1) amides and carbon tetrachloride in the presence of a base: CCI,

R,P.NHPh R,=Et,,

YO,

(OEt),, (CH,I2,

R

R

[R 28

ae

=

E12NI-1

But; Ar

=

R,Et,NP=N.Ph C Ef Me -0 -

/

,, or (CH,)2-O-

0

R

R R C,;H4-p-X(X = H, Me, OMe, NMe,, or F)] Scheme 1

R. Appel, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 1971, 104, 2250. E. E. Nifant'ev, G. F. Bebikh, and T. P. Sakodynskaya, J. Gem Chem. (U.S.S.R), 1971, 41, 2032.

212 Organophosphorus Chemistry A new synthesis of phosphazenes from o-aminophenols and tertiary phosphines has been developed,30which is believed to proceed by addition of the phenoxyl radical, formed by reaction with oxygen, to the phosphine. A possible route is shown in Scheme 1. Good evidence for the formation of the phenoxyl radical was obtained by examination of the e.s.r. spectra of reaction mixtures. 3 Properties of Acyclic Phosphazenes Halogeno-derivatives.-Studies of the alcoholysis of halogenomonophosphazenes have provided some interesting chemistry. For example, in the methanolysis 31 of the N-phosphinothioyl derivative F,P(S). N=PF2Cl hydrogen chloride is evolved, suggesting that reaction occurs initially at the phosphazenyl group. This result might also be expected on the basis of previous studies of the reactivity to amines. However, i.r. and 31Pn.m.r. spectroscopy show unambiguously that the product is the methylthiocompound F2P(0).N=PF,SMe, presumably favoured by the presence of the P=O bond. The possibility of formation of the phosphazane isomer F2P(0).NMe. P(S)F, was eliminated since it was characterized from the reaction : F,P(S)-NMe*SnMe,

+ [F,P(O)],O

----+ F,P(O).NMe.P(S)F,

+ Me3Sn.0.P(0)F,

The products of methanolysis and ethanolysis of a range of N-phosphinothioyl-phosphazenes, X1,P(S). N=PX2&1 (Xl and X2 include Cl and F), have since been shown32to have analogous structures. The solvolysis of F,P(S)-N=PF,CI by carboxylic acids may occur in different ways, depending on the nature of the acid employed: F2P(S)*NH.P(0)F, + HCoP

CO

+

HCI

MeCoa +

F, P (S1.N =P F, C1

F,P(S)-NH-COMe

-

P(O)F,CI

N.m.r. and mass spectrometry show that the alcoholysis of N-sulphonylphosphazenes also occurs 33 at the phosphazenyl group: XS02*N=PCI3

+ ROH

XS02. N=PC12 * OR (R = Me, Et, PP, or Bun)

and that, in the presence of catalytic quantities of diethyl ether, these rearrange to the dichlorophosphinyl derivatives, X*SO,. NR- P(O)Cl,. Possible mechanisms for these rearrangements were discussed. In a closely 30 31

32

H. H. H. H.

B. Stegmann, F. Stocker, and G. Bauer, Annalen, 1972, 755, 17. W. Roesky and L. F. Grimm, Chem. Comm., 1971,998. W. Roesky, B. H. Kuhtz, and L. F. Grimm, 2. anorg. Chem., 1972, 389, 167. W. Roesky and W. Grosse-Bowing, Chem. Ber., 1971, 104, 3204.

213

Phosphazenes

related series of reactions the alcoholysis of the monophosphazenes Y*N=PX3 (Y = MeSO,, C1S02,or N3P3F5;X = F or Cl) was followed.34 The alkoxy-phosphazenes again rearranged in the presence of diethyl ether to give derivatives of the type X,P(O)-NR*Y, with the exception of the derivatives of cyclophosphazenes in which the N3P,F5 N=PX20R structure appears to be stabilized by the presence of the formally unsaturated ring system. However, when the phosphazene linkage was more remote from the ring system, the rearrangement was again observed:

By comparison of these and other reactions with water and silylamines, it

was shown that the reactivity to nucleophilic attack at a phosphazenyl phosphorus atom generally decreased in the order : -N=PF,Cl

> -N=PF3

> -N=PCl,

> -N=PF,NMe,

-

> -N=PC12NMe2

The reactions of sodium t-butyl peroxide with N-sulphonylmonochlorophosphazenes follow 35 the expected course: ArSO,. N=PPh,Cl

+ NaOOBut

ArSO,. N=PPh,OOBut (Ar = C,H,-p-X; X = H, C1, Me, or NO,)

However, phosphoramides were obtained in reactions with analogous dichlorophosphazenes, probably as a result of the presence of traces of water in the reaction mixture : ArSO,.N=P(Ph)Cl,

+ NaOOBut + H 2 0

ArSO,.NH.P(O)(Ph). OOBut (same Ar substituents as above)

Large numbers of N-chloroacyl- and N-aroyl-P-amino-monophosphazenes, RCO N=P(NHR)3-nCln and compounds of closely related structure have been synthesized 36-41 from the analogous P-trichlorophosphazenyl derivatives, because of interest in their herbicidal and fungicidal activity. It is worth noting that in certain cases anionic species containing the phosphazenyl group may be obtained 38 by reactions 379

s4

36 36 37

s8 sD

41

H. W. Roesky and W. Grosse-Bowing, Z. anorg. Chem., 1971,386, 191. T. I. Yurzhenko and A. G. Babyak, J. Gen. Chem. (U.S.S.R.), 1971,41, 1460. V. P. Rudavskii, V. I. Kondratenko, and M. N. Kucherova, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1462.

V. P. Rudavskii and V. I. Kondratenko, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2176. V. P. Rudavskii and V. I. Kondratenko, J . Gen. Chem. (U.S.S.R.), 1971,41,2425. V. P. Rudavskii and N. A. Litoshenko, Khim. Tekhnol. (Kiev), 1971, 48 (Chem. Abs., 1972, 76, 45 845q). V. P. Rudavskii, N. A. Litoshenko, and D. M. Zagnibeda, Khim. Tekhnol. (Kieu), 1971, 19 (Chem. Abs., 1971, 75, 129 895y). V. P. Rudavskii, M. N. Kucherova, and D. F. Shirankov, Khim. Sel. Khoz., 1971, 9, 453 (Chem. Abs., 1971, 75, 108 815g). 8

-

214 with aniline and triethylamine: R.CO-N=PCl,

+ PhNH, + Et,N

Organophosphorus Chemistry

[Et,NH]+[R. CO. N=PC12NPh](R = various chloroalkyl groups)

Reactions of P-chlorophosphazenes with aziridine are also facilitated 42 by the presence of triethylamine : R1R2N=CR3*N=PPhCI,

+ HNC2H,

Et3N

R1R2N=CR3* N=PPh(NC,H,), (R1 = CF, or CCl,; R2 and R3 include O-CO-Alk and CN)

The dialkylaminodichlorophosphazenesPhN=PC12NEt2 form diphosphates on reaction with dialkyl- and diaryl-ureas :43 (R'NI-I) CO

PhN=PCI,NR1, (R1= Et, R2 = Me;

PhNH(R1,N)P(O). 0.P(0)(NR1,)NHPh R1 = Et, R2 = Ph; R1 = Bun, R2 = Me)

The i.r. spectra of the reaction mixtures suggest that are carbodi-imides, R2N=C=NR2, are intermediates in these reactions, although their precise function is not clear. The products of these reactions may also be obtained by controlled hydrolysis of the phosphazene : PhN=PC12-NR12

+ H20

EtsN

-

[PhNH P(0)NR1,],O

The reactions between N-chloroalkylphosphazenes and aldehydic compounds are complex, but generally give imides :44 for example, reactions with dialkylformamides may be formulated : CCI,. CCl,-N=PCI,

+ 2R2N*CH0

. +

CCI,. CO C1 R2N.CHCI, (R = Me or Et)

+ R,NCH=N - POCl,

It seems likely that these reactions proceed via the formation of salt-like complexes, related to those formed in the reactions of dialkylcarboxamides with phosphoryl chloride, e.g. [Me2N.CR. 0.P(O)Cl,]+ C1-. The products from these reactions were compared with those from the reactions of various N-arylsulphonylphosphazenes,ArSO,. N=PC13, with DMF. It is surprising that the phosphazene linkage is not retained when PhN=PCl,NEt2 is fluorinated 45 by antimony trifluoride, PhN=PC12NEt2

+ (excess)SbF,

-

Et,NPF4 42

+ SbC13 + Sb + by-products

L. D. Protsenko, N. Ya. Skul'skaya, and N. D. Bodnarchuk, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1250.

43 44

M. Bermann and K. Utvary, Synth. Inorg. Metal-org. Chem., 1971, 1, 171. V. P. Kukhar', V. Ya. Semenii, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1465.

46

M. Bermann and J. R. Van Wazer, Angew. Chem. Internat. Edn., 1971, 10, 733.

21 5

Phosphazenes

since the cyclophosphazene ring system is generally quite stable to this reagent. Relatively little interest has been shown in the chemical properties of the dimeric monophosphazenes (cyclodiphosphazanes) during the past year. The dimer, (MeNPCI,),, is fluorinated46 by boron trifluoride to give the difluoride, (MeNPCI,F),, with fluorine atoms in axial positions of the approximately trigonal-bipyramidal distribution of bonds about the phosphorus atoms. The same substrate reacts with chlorine under the influence of U.V. irradiation to give 47 the analogous trichloromethyl derivative in which the nitrogen atom is too weakly basic for dimer formation : c1,-U.V.

(MeNPC13)2 CCla soh?

CCl,. N=PCl,

An interesting analogy has been drawn48between the existence of the imino-isocyanate equilibrium R2C=N. COCl

R,CCl. NCO

and that which obtains between certain monophosphazenes and phosphorus(v) isocyanates : (CI,C),CI,P* NCO

-

(Cl,C),ClP=N- COCl

The latter tautomeric mixture was obtained by heating the products from the reaction of the monophosphazene (Cl,C),CIP=NH with oxalyl chloride to 120 "C. The i.r. spectrum of the tautomeric mixture showed that the concentration of the phosphazene form increased as the temperature was lowered in carbon tetrachloride solution. Experimental details of the decomposition of the N-sulphonylphosphazene Cl,P=N* S0,Cl to give the sulphur-nitrogen ring compound (NSOCI,) have been given.49 N-Sulphonylphosphazenes of related structure have been prepared60 by the reaction:

+

-

[C12PR1R2]+C1- H2N*S02Cl R1R2P(Cl)=N- S0,Cl [R1 included C1, Me, and Ph; R2 included C1, Me, Ph, N=PCl,, N=PCI, * N=PCI,, N=PCI(N=PCl,),, N=PPh,Cl, N=CCl. N=PCl,, and N=C(N=PCI,),]

A useful compilation of 31Pn.m.r. data for these derivatives, and for acyclic phosphazenes of related structure, was also given. An upfield 46

47

48

4@

H. Binder, 2. anorg. Chem., 1971, 384, 193. E. S. Kozlov and B. S. Drach, Ref. Zhur. Khim., 1970, Abs. No. lOZh 530 (Chem. A h . , 1971, 75, 88 033v). 0. I. Kolodyazhyi, L. I. Samarai, and S. N. Gaidamaka, J. Gen. Chem. (U.S.S.R.), 1971,41, 1879. T. Moeller, T.-H. Chang, A. Ouchi, A. Vandi, and A. Failli, Inorg. Synrh., 1972, 13, 11. W. Haubold and E. Fluck, 2. Naturforsch., 1972, 27b, 368.

216 Organophosphorus Chemistry trend in 31Pchemical shifts for the monophosphazenes (CCl,),ClP=N* Alk has been related to an opening of the P=N-C bond angle, deduced61 from vibrational spectra and from dipole moment measurements. These upfield shifts also corresponded to increases in the P=N bond order. The 19Fn.m.r. spectra of a series of dimeric monophosphazenes, (F,YPNMe), (Y = F, Me, Et, or Ph), have been obtained 62 over a range of temperatures and used to obtain information on P-N-P coupling constants, molecular conformations, and intramolecular exchange processes. An introductory account 53 of the n.m.r. spectra of monophosphazenes and cyclodiphosphazenes has been given, including a discussion of the upfield 31Pchemical shifts observed on passing from monomers, Cl,P=NR, to dimers, (CI,PNR), (R = fluorophenyl). lH and 31Pn.m.r. data on the structurally related dimers (X,PNMe), (X = C1 or F) have also been Alkyl and Aryl Derivatives.-The cleavage of silicon-nitrogen bonds in N-silylphosphazenes by reactions with phosphorus and silicon halides has been studied in some detail. For example, with phosphorus trichloride a novel tri(phosphazeny1)phosphine is obtained :55 Me,P= N Si Me,

Pc13

(Me,P=N),P

0

A similar reaction occurs with dichloromethylphosphine, but with chlorodimethylphosphine an unexpectedly facile quaternization reaction occurs, so that the N-dimethylphosphinophosphazene,Me,P=No PMe,, is not observed: Me,P=N-SiMe, Me,P=N-SiMe,

+ MePCl, + Me,PCl

-

(Me,P=N),PMe

1

[Me,P=N.PMe,] MetPCl

-

Me,P=N(PMe,), C1-

An analogous result is observed with the sulphur imide Me,S(O)=N. SiMe,: Me,S(O)=N. %Me,

+ Me,PCl

+

Me,S(O)=N(PMe,), C1-

In contrast, the reactions of N-silylphosphazenes with methyl- or phenylfluorophosphoranes R,PF5-, (n = 1 or 2) do not give phosphazenyl51 s2 53

66

E. S. Kozlov, S. N. Gaidamaka, Yu. Ya. Borovikov, V. T. Tsyba, and A. V. Kirsanov, J . Gen. Chem. (U.S.S.R.), 1970, 40, 2539. R. K. Harris, J. R. Woplin, R. E. Dunmur, M. Murray, and R. Schmutzler, Ber. Bunsengesellschaft phys. Chem., 1972, 76,44. K.Utvary, Allg. prakt. Chem., 1971, 22, 301 (Chem. Abs., 1972, 76, 52 568e). H.G. Horn, Chem.-Z., 1971, 95, 849. W. Wolfsberger, H. H. Pickel, and H. Schmidbaur, Z . Naturforsch., 1971, 26b,979.

Phosphazenes

-

[RPF(N=PPri,),]+ [RPF,](R = Me or Ph)

-----+

[Me,P(N=PMe,),]+

217

phosphoranes, but phosphonium ~ a l t s57, e.g. ~~~ RPF, RPF,

+ Me,Si. N=PMe,Ph + Me,%. N=PPri3

Me,PF,

+ Me,%. N=PMe,

[RP(N=PMe,Ph),]+ [RPF5](R = Me or Ph)

[Me,PF,]-

The 31Pchemical shifts of these salts suggest that the phosphonium ions are stabilized by conjugation between the phosphazenyl groups and the central phosphorus (P+) atoms. With methylfluorosilanes, N-silylphosphazenes undergo exchange reactions leading to N-methylfluorosilylphosphazenes in high yield Me,P=N.SiMe,

+ Me,SiF,-,

-

Me,P=N. SiMe,F,-, (n = 0, 1, or 2)

The di- and tri-fluorides may be obtained by fluorination of the analogous (n = 0 or l), which were obtained chlorides, Me,P=N*SiMe,CI,-, independently. The mono- and di-fluorides were monomers, but molecular weight and n.m.r. measurements showed that the trifluoride is a dimer with five-co-ordinated silicon atoms (13). Bis(trimethylphosphazeny1)dimethylsilane, (Me,P=N),SiMe,, gives crystalline 1:1 complexes with

I PMc~

M M

=

=

(13)

Zn; R Cd;R

=

=

Me or Et Me

(14)

dimethyl- and diethyl-zinc, as well as with dimethyl~admiurn.~~ Spectroscopic data suggest that the diphosphazene acts as a bidentate ligand, so that structures of the complexes are as shown in (14). The addition of triphenylphosphazene to a large number of isocyanates has been studied.60 Typical examples of these reactions are: Ph,P=NH

+ RNCO

-

RNH.C0.N=PPh3

[R = aryl, PhSO,, Me,Si, Si(NC0)3, Cl,P(O), or (MeO),P(O)]

+ Si(NCO), + Cl,P(O)NCO

Ph3P=NH (excess) Ph,P=NH (excess)

----+

Si(NH. C O . N=PPh,),NCO

(Ph,P=N),P(O)* NH. CO . N=PPh,

66 5' 5* 69

Bo

W. Stadelmann, 0. Stelzer, and R. Schmutzler, Chem. Comm., 1971, 1456. W. Stadelmann, 0. Stelzer, and R. Schmutzler, Z . anorg. Chem., 1971, 385, 142. W. Wolfsberger, H. H. Pickel, and H. Schmidbauer, Chem. Ber., 1971, 104, 1830. H. Schmidbaur and W. Wolfsberger, Synth. Inorg. Metal-org. Chem., 1971, 1, 111. A. S. Shtepanek, V. A. Zasorina, E. N. Tkachenko, and A. V. Kirsanov, Dopouidi Akad. Nauk Ukrain. R.S.R., Ser. B, 1971, 33, 153 (Chem. Abs., 1971, 75, 76944e).

21 8

-

0rganophospho r us Chemistry

The ease with which methyl iodide diquaternizes di(ary1phosphazenes) depends 61 on the separation of the phosphazenyl groups: CH,(Ph,P=NPh),

+ (excess) Me1

(CH,Ph,P=NPh),

+ (excess) Me1

-

(PhN=PPh,. CH,PPh,. NPhMe)+ I(CH,Ph,P- NPhMe),,+ 21-

Pretreatment of the monomethylenediphosphazene with sodium or n-butyl-lithium, followed by methyl iodide, resulted in the formation of a methylenephosphorane, (MePhN. PPh2=CH. PPh,MePh)+ I-. The same compound could also be converted into an imide by reaction with an aldehyde: CH,(PhZP=NPh),

+ 2OZN-p-CGH4CHO

-

CH,(Ph,PO)Z

+ 20,N-p-C,H,CH=NPh

The fact that the monomethylene derivative above only forms a monoquaternary salt may be contrasted with the fact that the diphosphine (Ph,P),CH, forms a diquaternary salt and that the phosphino-phosphazene, Ph,P(=NC6H4X).CH2PPh2 (X = H, p-Br, p-Me, rn-Me, p-OMe, or rn, p-NO,), is preferentially quaternized at the tervalent phosphorus atom.s2 The basicities and quaternization behaviour of these compounds were examined and it was shown that the diphosphazenes [Ph,P(=NC,H,X)],CH, are diacid bases, whereas the diphosphines such as (Ph,P),CH, are monoacid bases. Some of these features are also discussed in an extensive review 63 of the base properties of monophosphazenes, both from chemical and physical standpoints. The P=N bond orders of a series of monophosphazenes have been estimated utilizing 31P chemical shifts.64 As might be anticipated, the order increased with increasing electronegativity of the substituents on phosphorus and decreasing electronegativity of the substituents on nitrogen. The charge distributions and electron energies have been calculated by a self-consistent Hiickel method for phosphazenes of the type (p-X-C,H,),P=N-C,H,-p-NO, (X = H, C1, or NMe,) and (15) and have been Huckel-type MO calculations have compared with their U.V. also been carried out on other N-nitrophenylphosphazenes,66and the 81

62

63 64 85

Yu. V. Kovtun, V. A. Gilyarov, and M. I. Kabachnik, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 2217 (Chem. Abs., 1972, 76, 46454h). V. Yu. Kortun, V. A. Gilyarov, B. A. Korolev, E. I. Matrosov, and M. I. Kabachnik, J . Gen .Chem. (U.S.S.R.), 1971, 41, 777. M. I. Kabachnik, Phosphorus, 1971, 1, 117. A. S. Tarasevich and Yu. P. Egorov, Teor. i eksp. Khim., 1971, 7, 828 (Chem. Abs., 1972, 76 106 144j). H. Goetz and F. Marschner, Tetrahedron, 1971, 27, 3581. Yu. P. Egorov, V. V. Pen’kovskii, and B. N. Kuzminski, Teor. i eksp. Kltim., 1971, 7, 601 (Chem. Abs., 1972,76, 52003s).

219

Phosphazenes

X

=

II, C1, or NMc,

(15)

extent of m--bonding between nitrogen and phosphorus estimated 67 from the e.s.r. spectra of the anion-radicals of these phosphazenes. The polarographic method of producing these radicals has been described,6sin which reduction occurs at the nitro-group before the phosphazene linkage. Reaction of the phosphazenyl salts [Ph,(H,N)P-N=P(NH,)Ph,]+ (= L) C1- with cobalt(@ or copper(I1) chlorides gives 6B salts of the type L,CoCI, and L,Cu,Cl,, as well as some of their addition compounds with methanol or methylene chloride. Their e.s.r., u.v., visible, and i.r. spectra were discussed. Studies of the reactions of alkoxyphosphazenes with acid chlorides continue. Thus ethoxyphosphazenes are converted 70 into phosphinylamines on reaction with both phosphinyl and silyl chlorides:

4 Synthesis of Cyclic Phosphazenes The compounds Bu,SnCl,, (BuO),Ti, and MePhSiCl, act as catalysts for the preparation of chlorocyclophosphazenes from ammonium chloride and phosphorus penta~hloride.~~ Yields of the methylchlorocyclophosphazenes (NPClMe),,, from the reaction nMePC1,

+ nNH,Cl

-

(NPClMe),

have been improved7, to give up to 58% of cyclic products, by the preparation of finely divided ammonium chloride in situ. Similar findings have previously been reported for the series (NPCI,),. Improvements in the synthesis of the dimethylcyclophosphazenes(NPMe2)3,4have also been 67

V. V. Pen’kovskii, Yu. P. Egorov, and I. N. Zhmurova, Teor. i eksp. Khim., 1970, 6, 819 (Chem. Abs., 1971,75, 13 261j). V. V. Pen’kovskii, Yu. P. Egorov, and G. S. Shapoval, J. Gen. Chem. (U.S.S.R.), 1971, 41, 742.

70

71 72

R. M. Clipsham and M. A. Whitehead, Caiiad. J. Chem., 1972, 50, 75. V. A. Gilyarov, N. A. Tikhonina, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1971,41, 2380.

V. V. Kireev, G. S. Kolesnikov, V. P. Popilin, and S. M. Zhivukhin, Trudy Mosk. Khim.-Tekhnol. Inst., 1970, 157 (Chem. Abs., 1971, 75, 94 201q). V. N. Prons, M. P. Grinblat, and A. L. Klebanskii, J. Gen. Chem. (U.S.S.R.), 1971, 41, 475.

220 Organophosphorus Chemistry ~uggested.’~The tetramer is formed via a dihydrochloride, rather than the mixture of acyclic oligomers as previously reported, and yields of ca. 67% have been obtained by flushing the reaction mixture with nitrogen, followed by treatment with triethylamine to remove the last two molecules of hydrogen chloride : NH4Cl

+ Me,PCl,

---+

-

N4P4Me8,2HCl

EtaN

’

-

N4P4Me8

An alternative route to the tetramer (mixed with trimer) is to ammonolyse dimethyltrichlorophosphorane and pyrolyse the product in uacuo : Me,PC13

+ NH,

Me,P(NH,),Cl

A

(NPMe&

Several novel syntheses of new types of cyclophosphazenes have been described. For example, the mono- and di-phosphazenes H2N(R2N)2P=NH (R = Et or Bun) and (16) may be used to insert mono- and di-phosphazene units, respectively, into the triazine molecule (1 7).74 Thus in refluxing benzene solution ammonia was evolved leaving the cyclophosphazatriene (1 8) and the cyclodiphosphazatriene (1 9). lH and 31P NMe,

I

NMe,

I

H,N-I‘=N-I‘=NH I I NMe, NMc,

H N/‘\N II I HC, ,CH N’

H N/C, N II I (R2NN),I‘, ,CH N

n.m.r. spectroscopy showed that both (18) and (19) were quaternized by methyl iodide at the ring nitrogen atom(s) most remote from the phosphorus atom(s). This result would not have been expected had increases in basicity paralleled increased reactivity to methyl iodide, for the cyclotriphosphazatrienes (20) are considerably stronger bases than the triazine (17). The cyclization of linear diphosphazenes can be effected by reaction with trisdirnethylaminoph~sphine.~~ As in the reactions previously reported involving the same diphosphazene and phosphites, (21) was present as the P-H rather than the N-H tautomer. In a related series of reactions it 7s 74 75

F. A. Cotton and A. Shaver, Inorg. Chem., 1971, 10, 2362. A. Schmidpeter and A. Weingand, Angew. Chem. Znternat. Edn., 1971, 10, 397. A. Bermann and J. R. Van Wazer, Znorg. Chem., 1972, 11, 209.

22 1

Phosphazenes

Me,"

(H,N),C=N.C(=NH)(NR'R2)

+

XP(OI'h)2 ---+

'H (21)

H ,N -c/N+c-N R1 KZ II I N y N / \

X H X included Me and Et R1included H and M e R2included H , Me, Ph, Me-p-C,I-I,, and CI-p-C,H,

(22)

was shown76that biguanidines are cyclized by phosphites to give cyclophosphazatrienes (22). It was suggested that the P-H tautomer (22) is stabilized by incorporation of the electrons in the phosphazene rr-bond in the ring rr-system. The P-H bond readily enters into reactions with carbonyl compounds and with carbon tetrachloride, which replaces hydrogen by chlorine. These chlorine atoms may in turn be replaced by amino- or alkoxy-groups : -p<

Me H

+

R3- CO - R4

d

/Me "CR3R40H

(R3and R4include H, CH, and CCI,)

The structure of the major product from the reaction of chlorodiphenylphosphine with hydrazine hydrochloride has now been shown" to be (23 ; X = Cl), rather than the linear phosphazene (H2N.Ph2P=N. Ph,P=N-Ph2PNH2)+C1-. A number of other salts based on [(23); X = I,

76

7'

J. Ebeling, M. A. Leva, H. Stary, and A. Schmidpeter, Z . Naturforsch., 1971,26b,650. A, Schmidpeter and K. Stoll, Phosphorus, 1971, 1, 101.

222

Organophosphorus Chemistry

SCN, BPh4, +CuC14,or I (without H,0)] were also obtained. The elements of hydrogen chloride were removed from (23; X = C1) by sodium methoxide and the hydrated base was quaternized by methyl iodide at the phosphazene nitrogen atom in the resultant -NH. N=PPh2grouping. The sulphonyldiphosphazene SO,(N=PCl,), and some of its bis(dialky1amino)-derivatives are readily aminolysed by trimethylsilylamines to give both acyclic and cyclic p r o d ~ c t s79, ~as ~ ~shown in Scheme 2. A

/

O,S(N=PCI,N R’R’), (R*and R2 include I+ and alkyl groups)

$@-

O,S(N=PCI,),

-

IN= pc12 \ 02S, /NMe

Me ,Si NI I M c

N= PCl,

/

0,S,

\

(R = Me or Et)

NR N=P-CI \ CI /

CI

O,S(N=PCI,NR,),

(Me Fi).NMe

A

N = P-NR., i \ O,S, NMe /

N=P-NR, \

CI

(as a mixture o f geomctrical

isomers)

Scheme 2

monomethylamino-derivative of the diphosphazene is apparently difficult to obtain, since hydrogen chloride is readily eliminated, with simultaneous cyclization, in the reaction with Me,Si NHMe. The six-membered-ring compound (24) has only recently been obtained,80in low yield. The reaction of a salt, containing the same cation, with methylamine hydrochloride has been shown to give a known boron heterocycle (25). The same pro$uct was also obtained from methylamine hydrochloride and C13GNMePCI,. 78 79

U. Klingebiel and 0. Glemser, Chern. Ber., 1972, 105, 1510. U. Klingebiel and 0. Glemser, Chem. Ber., 1971, 104, 3804. U. Klingebiel and 0. Glemser, Z . Naturforsch., 1972, 27b, 467. H. Binder, Z . Naturforsch., 1971, 26b, 616.

(26)

With arsenic trifluoride, [CI,P=N* PC13]+ [BCI4]- is fluorinated to give (26), formulated as an adduct of N3P3F6and three molecules of phosphorus pentafluoride.*, This is an unexpected result, since it was previously indicated that N,P,F, does not form a stable adduct on direct addition of phosphorus pentafluoride. The reactions of the iminophosphines X2P*N= CPh, with electrophilic olefins provides a route to the first examples of phosphazenes (27) contained X2P.N=CPh,

+

CH,=CH.R

-

/N, \ ICPh2 C-CH H, R X included Me, Ph, and OMc R included CN and C0,Me (27)

within a five-membered-ring formed by 1,3-dipolar addition reactions. lH N.m.r. data are consistent with this structure and indicate that both the methylene protons and the X groups are non-equivalent.

5 Properties of Cyclic Phosphazenes General.-A review of the nature of the bonding in cyclophosphazenes has appeared,s4 which still proves to be a controversial subject. Although A the P-N bond lengths and RPR angles in cyclotriphosphazatrienes, N3P3R6,were shown to correlate linearly with Pauling electronegativity 8a 88

84

H. Binder, 2. anorg. Chem., 1971,383, 130. A. Schmidpeter and W. Zeiss, Angew. Chem. Internat., Edn. 1971, 10, 396. D. P. Craig and N. L. Paddock, Nonbenzenoid Aromatics, 1971, 2, 273 (Chem. Abs., 1972, 76, 13 282n).

224

Orgarzophosplzovus Chemistry

values, the same molecular parameters for cyclotetraphosphazatetraenes, N4P&, are best related to orbital electr~negativities.~~ Further details of the electrolytic reduction of aryl- and aryloxy-cyclophosphazenes in nonaqueous media have been given.86 Reduction was accomplished primarily at the organic groups by polarographic means and the resultant radical ions were observed by e.s.r. spectroscopy. Attempts to reduce halogenocycl ophosphazenes resulted in ligand ionization or decomposition. The temperature dependence of the electrical resistivity of a variety of halogenocyclophosphazenes and their derivatives has been

Halogeno-derivatives.-The results of the Faraday effect (rotation of the plane of polarized light in a magnetic field) and MO calculations (CND0/2 approximation) for the halogen derivatives N3P3C16,N3P3Fo, and N4P4F8support 8 8 the localized r-bonding scheme originally proposed by Dewar et al. Molecular d-orbital exponents for the same cyclophosphazenes have also been determined,89 and used to obtain bonded overlap values.g0 The latter correlate favourably with P-N bond lengths and with P-N stretching frequencies for the relevant cyclophosphazenes. These results were also used to predict that the [Cl3P=N*PCl3]f ion A

would have an PNP angle of 150-1 55". New self-consistent-field calculations on N3P3F6 and N4P4F8revealg1 remarkably high P-P intra-ring bond orders, e.g. 0.64 compared with 1.18 for P-N in N3P3F6, which should be important in determining the relatively high stability observed for these compounds. Details O2 of the i.r. spectra of 15N-labelledN3P3C16 have appeared, enabling some ambiguities in vibrational assignments to be clarified. The first example of a metal carbonyl complex of N3P3C16has been obtained 93 by the reaction: By analogy with the structure of hexaethylborazine tricarbonylchromium it was suggested that the bonding to cobalt is of the arene n--complex type. N3P3C16 also forms complexes with pyridine g4 and DMF,95 whose 8B 86

87

88

91

9a

93 94

95

A. J. Wagner, J. Znorg. Nuclear Chem., 1971, 33, 3988. H. R. Allcock and S. J. Birdsall, Znorg. Chem., 1971, 10, 2495. T. Hayashi and H. Saito, Kogyo Kagaku Zasshi, 1971,74, 1348 (Chem. Abs., 1971,75, 113 651e). J.-P. Faucher, J. Devanneaux, C. Leibovici, and J.-F. Labarre, J . Mol. Structure, 1971, 10, 439. R. M. Clipsham and M. A. Whitehead, J . C. S. Faraday ZZ, 1972, 68, 55. R. M. Clipsham and M. A. Whitehead, J. C. S. Faraday IZ, 1972, 68, 72. D. R. Armstrong, G . H. Longmuir, and P. G . Perkins, J. C. S. Chem. Comm., 1972, 464. E. S. KOZIOV, D. P. Khomenko, and G. G . Dyadyusha, Spectroscopy Letters, 1971, 4, 343. N. K. Hota and R. 0. Harris, J . C. S. Chem. Comm., 1972, 407. T. P. Zeleneva, 0. B. Khachaturyan, and B. I. Stepanov, Trudy. Mosk. Khim.-Technol. Inst., 1970, 147 (Chem. Abs., 1972, 76, 18 398q). T. Hayashi and H. Saito, N@pon Kagaku Kaishi, 1972, 314 (Chem. Abs., 1972, 76, 112 628m).

225

Phosphazenes

conductivities and 31P n.m.r. data 95 were reported. A nionoisocyanatoNSO with oxalyl derivative was obtained from the reaction of N3P3F5* chloride :9e N3P3F5* NSO

(CoC1)r>

N3P3F5.NC0

Alcohols add to this isocyanate in the expected way and the products were converted to iminophosphazenes by reaction with phosphorus pentachloride : N3P3F5-NC0

ROH

PCls

> N3P3F5-N=C(Cl)R N3P3F5.NH*COR (R = Me, Et or Prn)

The chloroimine was preferentially ammonolysed and aminolysed at the C-imino-position to give derivatives of the type N3P3F5N=C(NR22)R1 (R1 = Me, R2 = H ; R1 = Et or Prn, R2 = Me). A bis(isothiocyanat0)although it is not yet established derivative of N3P3C16has been ~btained,~' whether the arrangement of isothiocyanato-groups is geminal or non-geminal :

-

MNCS

N3P3C1, N3P,Cl,(NCS)Z (M = NH, or K)

-

This derivative was characterized by its addition products with alcohols and with isopropylamine : N3P3Cl,(NCS)Z

XH

N,P3Cl4[NHC(X)S], (X = OMe, OEt, or NHPr')

N,P3C16may find use as a binder in electrophotographic plates.98

Amino-derivatives.-The monoamino-derivative N3P3F5-NH2reacts with boron trichloride to give the hydrolytically unstable triaminoborane (N3P3FSNH)3B.ggThe thermal decomposition of N3P3CI4(NH2),has been followed by differential thermal analysis :loohydrogen chloride is lost over the range 150-600 "C and the final product has an irregular threedimensional structure of approximate composition (P3N&. During attempts lol to prepare the hexakisamino-derivative N3P3(NH2)6,which is of interest as a flame retardant,loftlo2 a hydrochloride N3P3(NH2)6,HCl was isolated and found to be readily converted to the hydrate, H. W. Roesky and E. Janssen, Z . Naturforsch., 1971, 26b,679. T. Moeller and R. L. Dieck, Synth. Inorg. Metal-org. Chem., 1972, 1, 19. 98 A. B. 4midou, J. Mammino, and R. Radler, U.S.P.,3 607 261 (Chem. A h . , 1971, 75, 146 273m). H. W. Roesky, Chem. Ber., 1972,105, 1726, l o o A. F. Nikolaev, V. M. Bondarenko, and Yu. P. Belyaev, J . Gen. Chem. (U.S.S.R.), 1971, 41, 1032. lol E. Kobayashi, Bull. Chem. SOC.Japan, 1971, 44, 2280. loa D. R. Moore, S. E. Ross, and G. C. Tesoro, U.S.P., 3 317 220 (Chem. Abs., 1972, 76, 60 861k). 96

97

226

Organophosphorus Chemistry

N,P,(NH&H,O. Further examples of the use of aminocyclophosphazenes, [NP(NH2)]3,4,as fertilizers for cereal crops have appeared.lo39lo4 An extensive series of amino-, N,P,F5-NR1R2 (R1 = H, R2 = Et; R1 = RZ = Et, Prn, or Bun), and hydrazino-derivatives, N3P3F5NH. NR3R4 (R3 = R4 = H or Me; R3 = H, R4 = Me) has been obtained lo5by direct reactions of amines and hydrazines with N3P3F6. With derivatives of primary amines, reactions with silylamines occur at the amino-group rather than at the phosphorus atoms:

-

+

N3P3F5*NHR Me,Si.NEt,

-

N,P,F,*NR.SiMe, (R = Me or Et)

The physical properties of these derivatives measured included the P-N-P coupling constants, which were all within the relatively narrow range 109-1 15 Hz. Geometrical isomers of the non-geminal bisdimethylaminoderivative N3P3F4(NMe2)2 have been separated by g.l.c.lo6 and identified by dipole moment measurements. Antimony trifluoride fluorinates lo7 isomeric trisdimethylamino-, N3P3C13(NMe2)3,and tetrakisdimethylamino-, N,P,Cl,(NMe,),, derivatives, although fluorination is accompanied by isomerization. Thus fully fluorinated products were obtained as mixtures of isomers together with some chlorofluorodimethylarnino-derivatives. Purification of these isomers by g.1.c. and examination of their n.m.r. and vibrational spectra enabled structural assignments to be made, including that shown for the chloride-fluoride (28; X = F), which was obtained from the geminal

trichloride (28; X = C1) in 1,2-dichloroethane. This structure (28; X = F) shows that the EPClNMe, group is more readily fluorinated than the rPC1, group, consistent with the fact that the more highly aminolysed chlorides are fluorinated under the mildest conditions. It has also been found lo8that antimony trifluoride can effect the substitution of dimethylamino-groups by fluorine atoms in cyclic phosphazenes, although at a slower rate than the substitution of chlorine atoms. For example, L. Ondracek, K. Haas, and W. Wanek, 2. Pflanzenernaehr. Dueng. Bodenk., 1971, 128, 180 (Chern. Abs., 1971,75, 75 415w). l o 4 L. Ondracek, J. Hampl, F. Mondig, and W. Wanek, Agrochernia, 1971, 11, 177 (Chern. Abs., 1971, 75, 97 777t). lo5 E. Neicke, H. Thamm, and G. Flaskerud, Chern. Ber., 1971, 104, 3729. lo6 E. Niecke, H. Thamm, and D. Bohler, Inorg. Nuclear Chern. Letters, 1972, 8 , 261. lo' B. Green, D. B. Sowerby, and P. Clare, J . Chern. SOC. (A), 1971, 3487. l o * P. Clare, D. Millington, and D. B. Sowerby, J . C. S. Chern. Comm., 1972, 324. lo3

227

Phosphazenes

N,P,Cl,(NMe,), gave three isomeric pentafluorides, N4P4F5(NMe2)3,in addition to the expected tetrafluorides, N3P3F4(NMe2),. Fully aminolysed derivatives also form fluorodimethylamino-derivatives : SbFI

N4P4(NMe2)8

SbFi

N3P3(NMe2)6

' '

N4P4F(NMe2)7

+ N4P4F2(NMe2)tl

N3P3F(NMe2)Li

Reactions are slower with the six-membered-ring system and in both cases there is evidence for the non-geminal replacement of dimethylamino-groups by fluorine atoms. A re-examinationlo9 of the products of the reaction of N3P3C16with dimethylamine by g.1.c. has enabled the trans-tetrakis- and pentakisdimethylamino-derivatives [ (29) and (30), respectively] to be isolated, the

Me,N

NMe, (29)

former by fractional crystallization. Further new examples of the otherwise elusive monochloropentakisaminocyclophosphazenes have been by reactions with two different amines in ether solution: obtained N,P,Cl,NHR

MerNH

> N3P3(NHR)(NMe,),CI (R = PP, Bun, or Pent")

In chloroform solution the fully aminolysed products, N3P3(NHR)(NMe2),, were obtained. It was suggested that the reduced electron supply of the NHR group, relative to that of a dimethylamino-group, is sufficient to prevent a change in mechanism that apparently makes the isolation of the monochloro-derivatives difficult. The monochloro-derivatives were converted to monoalkoxides, and dihydrochlorides of the type N3P3(NMe2)5(NHR),2HCl (R = Prn, Bun, or Pent") were also isolated. New kinetic data on the reactions of chlorocyclophosphazenes with amines have appeared. The reactions of both N3P3C16and N3P3C15.NMe2 with dimethylamine in THF were shown by conductivity measurements to follow a second-order rate law, which was first order in dimethylamine.lll The formation of both mono- and bis-dimethylamino-derivatives was visualized as proceeding by the rapid formation of a five-co-ordinated intermediate, followed by a relatively slow entropy-controlled THFcatalysed dehydrochlorination. It was suggested that the entropy of log ll0 ll1

B. Green and D. B. Sowerby, J. Inorg. Nuclear Chem., 1971, 33, 3687. N. I. Shvetsov-Shilovskii and M. R. Pitina, J . Gen. Chem. (U.S.S.R.), 1971, 41, 1028. J. M. E. Goldschmidt and E. Licht, J. Chem. SOC.(A), 1971, 2429.

228

Organophosphorirs Chemistry

activation increases on going from the mono- to the bis-derivative, mainly because of increased ground-state solvation of the leaving chlorine atom owing to the electron-releasing effects of the substituent, and the participation of the substituent (NMe, group) in the solvation of the chloride ion (necessitating the substituent and the leaving chloride ion to be on the same side of the ring to form a trans-isomer). The reactions of N,P,Cl, with methylaminef12 to give the mono- and bis-methylamino-derivative are also second order and have a lower enthalpy of activation than reactions with dimethylamine, suggesting that steric effects are important. The loss of chloride ion is again entropy controlled and similar solvation effects to those proposed above may be operative here also. These results were compared 113 with those obtained for the reactions: N,P,Cl,- NHMe

N:cye’> N,P,Cl,(NHMe)(N Me,)


N3P,C15- NMe,

(non-geminal, assumed trans) The fact that the rate k, was almost equal to that for the reaction of N,P,Cl,-NMe, with dimethylamine and that k, was very similar to that of N,P,CI,.NHMe and methylamine was taken to indicate that the rate of aminolysis is largely dependent on the nucleophile, and independent of the substituents on the phosphazene ring. In the latter two studies rate measurements were made by potentiometric estimation of the chloride ion released in the reaction. NN’-Dimethylethylenediamine, MeNH(CH,),NHMe, effects the geminal replacement of fluorine1l41115 and chlorine115 atoms in N3P3X6 and N4P4X8(X = C1 or F) to give imidazolidino-derivatives (31; n = 3, x = 1 Me I

or 2; n = 4, x = 1). The analogous silylamine reacts more slowly, but geminal fluorine atom replacement is again observed (Scheme 3).

Alkoxy- and Aryloxy-derivatives.-A series of spirocyclophosphazenes has been prepared 116from the reactions of 1,s-dihydroxynaphthalenewith J. M.E. Goldschmidt and E. Licht, J. C. S . Dalton, 1972, 728. J. M.E. Goldschmidt and E. Licht, J. C. S . Dalton, 1972, 732. 114 T.Chivers and R. Hedgeland, Inorg. Nuclear Chem. Letters, 1971, 7 , 767. 116 T.Chivers and R. Hedgeland, Canad. J . Chem., 1972, 50, 1017. 11* H. R. Allcock and E. J. Walsh, Inorg. Chem., 1971, 10, 1643.

112

113

Phosphazenes

229 Me

Me

I

\

N3P,F,-

+

I

N-CH,

Me,S?-lH2 \ +N3P3F4< N-CH, N-CH, I / Me Me Scheme 3

)

N,P&& [to give (32) ] and N4P4C18,or by reacting 2,2'-dihydroxybiphenyl with N4P4C18[to give (33) 1. The expected spiro-derivative is also obtained from catechol and N3P3C16,but N4P4C18gives the phosphorane (34), as mentioned in a preliminary report. The formation of (34) is attributed

(34)

to the release of ring strain in the conversion of the phosphazene to the phosphorane with its five-co-ordinated phosphorus atom. The reasons for the differences in reactivity between N,P,Cl, and N4P4C18are less clear, but may be related to greater skeletal flexibility in the latter. The catechol derivative (35) is reported 11' to be useful in the purification of hydrocarbons

(35)

such as p-xylene, since it is capable of forming inclusion complexes, The reactions of the sodium salts of xylylene glycols with N3P,C16, to give N3P3(0CH2C6HaCH20)3 and N3P3(0CH2C6H4CH20H)6, are second 117

R. H. Anstey and H. G . Naylor, B.P. 1 257 024 (Chern. Abs., 1972, 76,33 927e).

230

Organophosphorus Chemistry

order.lls 31PN.m.r. data on these and the intermediate products have also been reported. Rate measurements have been carried out on the reaction of N,P,Cl, with benzyl alcohol, which gives 119 two different sets of products, e.g. N3P3C16 + PhCH,OH

/

[P(O)(OH)NH],

+

I'hCH,CI

N,P,(OCH,PII)~

+

I-ICI

The benzoyloxychloro-derivativesN3P3C16-n(OCH2Ph),(n = 1-5) were isolated and structural assignments made from their lH and 31P n.ni.r. spectra. The bis(trifluoromethy1)aminoxy-derivatives N3P3[ON(CF3)2]s and N4P4[ON(CF3)2]4have been prepared 120 by reactions of the sodium salt of bis(trifluoromethyl)hydroxylamine, (CF,),NONa, with N,P,Cl, and N4P4Cls,respectively. Hexakis(alkoxy)cyclophosphazenes, N,P,(OR),, undergo reactions with (chloromethy1)silanes at ca. 16@-180 "C to give silylalkoxycyclophosphazenes,121e.g.

-

+

N3P3(OB~n)6 C1CH,SiR1R2, N,P,(OBU")~OCH~S~R~R~~ (R1 and R2 included alkyl, aryl, and alkoxy-groups)

Although alkoxyphosphazenes rearrange to oxophosphazanes, there was no evidence that the analogous rearrangement :

occurred in this case. This was confirmed by comparison of the lH n.m.r. spectra of the products (R1 = Ph, R2 = Me) with that of N,P,(OBn),(OCH2SiMe2Ph), prepared by an independent route. The fact that the reaction was first order in N3P3(0Bun),and zeroth order in the silane, as well as catalysed by Lewis acids, led the authors to propose a mechanism for the reaction which involves heterolysis of the 0-C bond in the phosphazene as the rate-determining step, followed by rapid displacement /

of chlorine from the silane by the -N=P-0-

group:

\

\I

p-0-R

II N

119

120 121

\I

p-0-

7

II N

/

/

118

slowL

+

\I R';

P-0II

N

/

q CH,Si-/ p

Z

rast

F

\I P-0-CH,Si

+

i

/

-

\

/

M. Kajiwara and H. Saito, Kogyo Kagaku Zasshi, 1971,74, 2324 (Chem. Abs., 1972, 76, 45 4152). M. Kajiwara and H. Saito, Kogyo Kagaku Zusshi, 1971, 74, 619 (Chem. Abs., 1971, 75 , 34923s). P. 0. Gitel', L. F. Osipova, and L. I. Kostikin, J. Gen. Chern. (U.S.S.R.), 1971, 41, 1416.

V. V. Kircev, G. S. Kolesnikov, I. M. Raigorodskii, and P. 0. Okulevich, J . Gen. Chem. (U,,S.S.R.),1971, 41, 798.

23 1

Phosphazenes

Further details of studies concerned with the mechanism of alkaline hydrolysis of fluoroalkoxycyclophosphazenes have appeared.122 The hexakis(trifluoroethoxy)-derivative N,P,(OCH,CF,), was hydrolysed by a non-geminal pathway eventually giving small quantities of (36). The cyclophosphazene (36) rearranged in the presence of acid to give a cyclophosphazane (37; R = CH2CF3). The loss of the first alkoxy-group to

give N,P,(OR),(ONa) or N,P,(OR),(ONa) was second order and the rate was shown to decrease in the order : R = CH,C,F, > CHzCF3 > CH,C,F, in the trimer series. The tetramer derivatives were hydrolysed two to four times as fast as the analogous trimers, and hydrolysis in the presence of HZ1*0did not result in an l*O-containing alcohol. The mechanism of hydrolysis was therefore suggested to be of the S N type ~ involving a trigonal-bipyramidal transition state at phosphorus, with phosphorusoxygen rather than carbon-oxygen bond cleavage (Scheme 4). RO HO-+

OR

/ /

P

4\

OR I

+ HO-PLOR

4\

HO OR ---+

\p/ + J\

OR-

Scheme 4

N3P,Cl, reacts with DMF at 80°C to form a complex, formulated as [N3P3(0CH=NMe2)6]6+ 6C1-, which on further reaction with the sulphonic acid salts RS0,K (R = aryl or chlorosulphonyl) and, subsequently, water, gave N3P3(OH),, DMF, and RSOzC1.123

Aryl and Alkynyl Derivatives.-Full details of the complex range of products obtained from the reaction of N,P&l, with diphenylmagnesium in 1,4-dioxan have been p ~ b 1 i s h e d . l ~These ~ included N3P,Ph6, (38), (39; X = Ph), and (39; X = -N=PPh,). The solvating power of the solvent appears to be responsible for differences in the range of products in these reactions, and for that from the reactions with organomagnesium reagents in diethyl ether. Tentative suggestions for the mechanisms of formation of these products were proposed. The l9Fn.m.r. spectra of the 12a

lZs 12*

H. R. Allcock and E. J. Walsh, J. Amer. Chem. SOC.,1972, 94, 119. G. K. Gryzlova and B, I. Stepanov, Zhur. org. Khim., 1971,7, 619 (Chem. Abs., 1971, 75, 59918).

M. Biddlestone and R. A. Shaw, J. Chem. SOC.( A ) , 1971, 2715.

232

Organophosphorus Chemistry

fluoroaryl derivatives N,P,F2n-1Ar (n = 3-8; Ar = p-F-C,H, or m-F-C,H,) indicate125 that the phosphazene ring is capable of strong inductive and conjugative withdrawal of electron density, comparable with that effected by a cyano-group or a nitro-group. When Ar = C6F5, the difference in chemical shifts between the fluorine atoms in the paraand meta-positions is consistent with conjugation of the homomorphic n--system of the fluorophenyl group with the homomorphic n--system in the phosphazene ring. If the chemical shifts of the fluorine atoms bonded to phosphorus are a reflection of the n-electron densities at these phosphorus atoms, then their variation, as the ring size is increased in the series (NPF2), (n = 3-8), is characteristic of both homo- and hetero-niorphic contributions to the cyclophosphazene n-systems. The fluoroarylphosphazenes were all obtained by reactions of the relevant fluoroaryl-lithium with the fluorocyclophosphazenes in diethyl ether solution. It has previously been shown that the magnitude of the phosphorus-phosphorus coupling constant, 2J(P-N-P), in cyclophosphazenes may be predicted by an additivity relationship in which the coupling constant is a function of the substituents on the phosphorus atoms concerned. However, the 31Pn.m.r. spectra of the isomeric diphenyl derivatives N3P3F4Ph2 and of the geminal N3P3F2Ph4 show 12,that the relationship is not a general one. As in the reactions of N3P3F6with methyl-lithium, replacement of the first two fluorine atoms in the same substrate by phenylethynyl-lithium occurs by a predominantly geminal reaction path :12' N3P3F6

PhCGCLi + -0

N3P3F5C=CPh

0 "C,Eta0

gem-N,P,F,(C=CPh),

r3F5

The monophenylethynyl derivative reacts readily with dicobalt octacarbonyl to give the complex formulated as (40). OC,

/ \

F0

oc-co- -co-co oc/ 'c/ 'co P 11

(40 1 laS 126 12'

T. Chivers and N. L. Paddock, Znorg. Chem., 1972, 11, 848. C. W. Allen, J. Magn. Resonance, 1971, 5 , 435. T. Chivers, Inorg. Nuclear Chem. Letters, 1971, 7 , 827.

Phosphazer-ies

233

6 Polymeric Phosphazenes Further investigations into the nature of the oily -(NPC12)n- polymers 128 and their products with mono- and di-phenols 129 have been reported. In the latter case the initial stage of the reaction with Cl(Cl,P=N)9PCl, was second order and 31P n.m.r. suggested that m-cresol effected geminal replacement of chlorine atoms to give RO[Cl,P=N* (RO),P=N* PC12=N. PCl2=NI3P(OR), (R = m-tolyl). Examples of polymers derived from N3P3C16and biphenols have been 131 as well as the effects of the same phosphazene Lon the cross linking of p o l y c a r b o n a t e ~ ,and ~ ~ ~ the formation of p ~ l y s i l a n e s c, ~y ~ c l~o s i l ~ x a n e sand , ~ ~ branched ~ p01ystyrene.l~~ The presence of metals (incorporated as their salts) in polymers derived from N3P3(OH)6136 and N4P4(NH2)4Ph4 13' improved their thermal stability, and chlorophosphazene polymers containing metals have been obtained 138 by direct addition of the metallic elements to the ammonium chloridephosphorus pentachloride reaction mixture. Propan- 1-01s and propane1,3-diols give esters 139 with N3P3C16which are useful in the flameproofing of cotton and polyester textiles. The formation of copolymers from the hexa-n-butoxy-derivative N3P3(OBun),and the (chloromethy1)disiloxanes [Me(ClCH,),Si],O and [Me(ClCH,)Si],O at 150-170 "C follows 140 a first-order rate law. S. M. Zhivukhin, V. V. Kireev, G. S. Kolesnikov, and V. P. Popolin, U.S.S.R.P. 293 017 (Chem. Abs., 1971, 75, 36 990k). lz9 T. Hayashi and H. Saito, Kogyo Kogaku Zasshi, 1971, 74, 22 (Chem. Abs., 1971, 75, 538511). lSo K. Nakamura, Jap.P., 71 22 224 (Chem. Abs., 1972,76,4475a). lS1 H. Suzuki, Jap.P., 71 20831 (Chem. Abs., 1971,75, 130436f). lSa H. L. Rawlings, U.S.P. 3 597 394 (Chem. Abs., 1971, 75, 152 547v). 13) P. Haussmann and G. Greber, Angew. Makromol. Chem., 1971,16,325 (Chem. Abs., 1971, 75, 37 107q). IS4 S. Nitzsche and J. Burkhardt, G.P. 1955 514 (Chem. Abs., 1971, 75, 50 564f). 135 J. C. Meunier and R. Van Leemput, Makromol. Chem., 1971, 142, 1 (Chem. Abs., 1971, 74, 142 417t). 136 A. F. Nikolaev, N. A. Dreiman, and T. A. Zyryanova, U.S.S.R.P. 295 783 (Chem. Abs., 1971, 75, 64 658b). 13' R. M. Murch and T. Bieniek, U.S.P. 3 563 918 (Chem. Abs., 1971, 74, 126 427r). 138 E. Kobayashi, Jap.P. 71 00 805 (Chem. Abs., 1971, 74, 112 659f). 139 W. Rainer, G.P. 2 062 677 (Chem. Abs., 1972, 76, 101 1 4 2 ~ ) . 140 T. N. Beloglazova, V. V. Kireev, G. S. Kolesnikov, and I. M. Raigorodskii, Vysokomol. Soedineniya, Ser. A , 1971, 13, 1625 (Chem. Abs., 1971, 75, 118 814~). la8

Me,N

CI

/-\

Ph,P=N-SO,C,H,-p-Me

Compound A

P-6-N 1.607 (4) P-6-N 1.641 (4)

P-4-N 1.628 (4)

P-4-Cl 2.051 (2)

P-2-c1 2.014 (2) 1.992 (2)

P-2-N 1.554 (4) P-4-N 1.570 (4)

2.006 (3)

1.582 (5)

at P-6 113.1 (2)

at P-4 119.0 (2)

at P-2 120.7 (2)

-

142

Data consistent with Dsh symmetry. Previous crystal structure gave P-N = 1.57A

at P-6 103.7 (2)

at P-4 104.6 (1)

at P-2 99.6 (1)

Ring has distorted ‘boat’ conformation

144

143

141

Reference

Both P-N and S-N considerably shorter than the sum of the respective single-bond radii

Comments

101.5 (1.5) C,, Symmetry (slightly puckered ring) indicated, which may be a vibrational effect rather than the equilibrium conformation

1.543 (3.5) 121.4 (3.5) 98.0 (3.0)

XPX -

1.590 (13)

-

NSN

S-N 1.586 (4)

P-x

Averagea bond angles/

1.579 (8)

P-N

Averagea bond distanceslA

7 Molecular Structures of Phosphazenes Determined by Diffraction Methods A

-(NPF2)n-

152

151

150

148

14*

14'

146

145

144

143

142

141

1.581 (10)

2.175 (6)

1.57 (1)

1.571 (17)

1.655 (20)

As preliminary report (Vol. 3)

1.600 (10)

As preliminary report (Vol. 3)

1.644 (11)

1.543 (17)

-

120.5 (9) 114.3 (9)

121.0 (6)

120.2 (13)

120.1 (4)

-

103.3 (2)

105.5 (5)

100.1 (10)

103.9 (1)

A

Ring N atoms occupy four of the five co-ordination sites at Co"

Has pseudo-mirror plane passing through PBr, and opposite N atom. Ring puckered with one reentrant angle at N

'saddle' shape; av. POC, 121°, indicates .rr-bond between 0 and P

Ring has slightly distorted

tion av. PNC = 151.1 (9.0)

A

Ring has chair conforma-

Ring intermediate between 'boat' and 'saddle' forms

Standard deviations in parentheses. These structures determined by electron diffraction. All other structures were determined by X-ray diffraction.

A. F. Cameron, N. J. Hair, and D. G. Morris, Chem. Comm.,1971, 918. M. I. Davis and J. W. Paul, J. Mol. Structure, 1971, 9, 478. M. I. Davis and J. W. Paul, J. Mol. Structure, 1972, 12, 249. F. R. Ahmed and D. R. Pollard, Acta Cryst., 1972, B28, 513. H. R. Allcock, M. T. Stein, and J. A. Stanko, J. Amer. Chem. SOC.,1971, 93, 3173. H. Zoer and A. J. Wagner, Acta Cryst., 1972, B28, 252. J. B. Faught, Canad. J. Chem., 1972, 50, 1315. G. B. Ansell and G. J. Bullen, J. Chem. SOC.(A), 1971, 2498. G . J. Hartsuiker and A. J. Wagner, J. C. S. Dalton, 1972, 1069. W. Harrison and J. Trotter, J. C. S. Dalton, 1972, 623. W. Harrison, N. L. Paddock, J. Trotter, and J. N. Wingfield, J. C. S. Chem. Comm., 1972, 23. H. R. Allcock, R. L. Kugel, and E. G. Stroh, Inorg. Chem., 1972, 11, 1120.

(three fused P-N rings)

P6N7C19

2.171 (2)

1.575 (6)

152

151

150

149

148

147

146

10

Radical, Photochemical, and Deoxygenation Reactions BY

R. S. DAVIDSON

1 Radical and Photochemical Reactions The year under review has seen a number of applications of e.s.r. spectroscopy to confirm the formation of radicals postulated in a variety of reactions. Thus, in the reaction of t-butoxyl radicals with triethyl phosphite in cyclopentane solution, both phosphoranyl radicals and cyclopentyl radicals were detected (Scheme 1).l By comparison with ButO.

+ (EtO),P

Bu'OF(OEt),

--+ ButOfi(OEt),,

L

But *

+

(EtO),PO

Scheme 1

the rates of reaction of the t-butoxyl radicals with the phosphite and with cyclopentane, the rate constant for reaction of t-butoxyl radicals with the phosphite was determined as 1.6 x lo8 1 mol-1 s-l (at 30 "C). It was also noted that, in the presence of oxygen, phosphoranylperoxyl radicals were formed.2s3 These radicals have been proposed as intermediates in the autoxidation of alkanes run in the presence of phosphites (Scheme 2).3 The thio-radical (RO),PSi has been generated by irradiation of 00'-dialkyl dithiophosphates contained in a rigid r n a t r i ~ .The ~ structure of the radical was evident from its g-value and hyperfine splitting constants. The reaction of alkoxyl radicals (generated by photolysis of nitrite esters) with phosphites has been exploited in a new synthesis of phosphates of hindered alcohols.6 Another aspect of this radical reaction which has been investigated, has been an evaluation of the ease of 13-cleavage of axial and 1 2 9

4 5

A. G. Davies, D. Griller, and B. P. Roberts, Angew. Chem. Internat. Edn., 1971, 10, 738. A. G. Davies, D. Griller, and B. P. Roberts, J. C . S. Perkin ZZ, 1972, 993. G. B. Watts and K. U. Ingold, J. Amer. Chem. SOC.,1972, 94,2528. M. Sato, M. Yanagita, Y. Fujita, and T. Kwan, Bull. Chem. SOC.Japan, 1971,44, 1423. D. H. R. Barton, T. J. Bentley, R. H. Hesse, F. Mutterer, and M. M. Pechet, Chern. Comm., 1971,912.

236

Radical, Photo chernical, and Deoxygena tion Rea c t ions

-

K ' 0 2 * t P(OR'),, > ---+ RIO,P(OR~):~ K'O. + P(oR~), ---+ K I O F ( O R ~+) ~0, K'O( R'O),P02* + (R20),P ----+ R10(R20),POOP(OR2), R10(R20),PO* R'O- + R2H ~

237

K I 0 ,P(0 I<";{

R'O- t (RYI),IW

RIOP~R'):,

R~o(R~o),Po~. R'O( R20):,POOk(OR2):, R10(R20),PO* + (R20),P0 R'O. + (R20),P0 R'OH + R'* 0, -----+-R'O,* Scheme 2 ___f

R'*

+

equatorial alkoxy-groups contained in phosphoranyl radicak6 Apparently there is a 1.3:l preference for cleavage of axial groups. Examples have been found in which alkoxyl radicals and a few thiyl radicals react with phosphines and phosphites in a displacement reaction (Scheme 3) as well as bringing about oxidation.' Stable phenoxyl radicals, derived from o-aminophenols, have been shown to react with triarylphosphines to give phosphineimines [e.g. (1) Autoxidation (sensitized by AIBN) has been shown to occur more readily with phosphinites than with phosphites, which are in turn more reactive K ~ X . + R'P(OEt),

-

RIXf(OEt), A \

Scheme 3

6

'

--+R'P(:X)(OEt),

R 2

R X P (0Et ).

W. G. Bentrude and T. B. Min, J. Amer. Chem. SOC.,1972,94, 1025. W. G. Bentrude, E. R. Hansen, W. A. Khan, and P. E. Rogers, J. Amer. Chem. SOC., 1972,94,2867.

H. B. Stegmann, F. Stocker, and G. Bauer, Annalen, 1972,755, 17.

238 Organophosphorus Chemistry than triphenylph~sphine.~ In a study of the oxidation of triethyl phosphite by t-butylperoxyl radicals, the most interesting observation was made that methyl radicals (formed by /3-scission of t-butoxyl radicals) attacked the P=O of the phosphate ester at the oxygen atom (Scheme 4).1° Alkyl radicals attack phosphorus trichloride in a displacement reaction.ll The efficiency of this reaction depends on the stability of the radical (e.g. (a-cyanoisopropyl radicals do not react) and on the ease with which the radicals undergo disproportionation and recombination reactions.

Me-

+

(EtO),PO

hleOl%OEt),

MeO@(OEt),

d

MeOP(OEt),

It 0 Scheme 4

The reaction of vinyl chloride with phosphorus trichloride in the presence of oxygen has been re-investigated and the products shown to be (2) and (3).12

0,' CI,PO'

PCI,

Cl,I'(:O)O.CHCI.CH,CI

+

CI.

Several interesting phosphorus-containing radicals have been prepared by y-irradiation. The radical cations of phosphines, generated in this way, have been shown to react with the phosphines to give radicals of the type (4).13 In the case of the disulphide (9, the ejected electron was captured by the disulphide to give radical (6). The g-values and hyperfine coupling constants of a wide variety of radicals derived from phosphines, lo

l1

l2 l3

Y. Ogata and M. Yamashita, J. C. S. Perkin ZI, 1972, 730. Y. A. Levin, E. K. Trutneva, I. P. Goman, A. G. Abul'khanov, and B. E. Ivanov, Bull. Acad. Sci. U.S.S.R., 1970, 2687. L. Dulog, F. Nierlich, and A. Verhelst, Chem. Ber., 1972, 105, 874. C. B. C. Boyce and S. B. Webb, J. Chem. SOC.(C), 1971, 3987. A. R. Lyons, G. W. Neilson, and M. C. R. Symons, J. C. S. Chem. Comnz., 1972. 507.

239

Radical, Photochemical, and Deoxygenation Reactions R ~ P

y-iiiadiation

f

t.

IXJ

2 ’+

Mc,P-PMc, II II

s s

-

K ,I’

+ Rj-bfX3

M~,P-PMc~ II I s s-

(4)

phosphine oxides, and phosphinium salts have been determined.14 Radicals have been obtained from phosphines in which the radical centre is to the phosphorus atom [e.g. 2-(dialkylphosphinyl)ethyl] and strong coupling with the phosphorus was found.16 The coupling was thought to arise through hyperconjugation, i.e. there is interaction of the C-P bond with the radical. This suggestion was taken further l6 and it was very convincingly argued that the reactivity of an aromatic nucleus, having a substitue+nt of the type -CH,-X (where X = positively charged group such as R,P), towards electrophilic attack was due to stabilization of the Wheland intermediate (7) by hyperconjugation. A number of other systems were also

R

on radicals derived by y-irradiation of discussed. In two studies phosphoryl chloride, the radical derived by electron capture by the oxychloride was observed. The reactions of a number of phospholes with alkali metals have been investigated.l8.lo If the temperature of the reaction is kept low, C-P bond cleavage does not occur and radical anions (identified by e.s.r. spectroscopy) are formed.l* Increasing the reaction temperature leads to C-P bond cleavage and the formation of metal phosphacyc1opentadienides.lO Various alkylation reactions were carried out with these compounds. Alkali metals reduce phosphole oxides to their radical anions.2o The radical anions formed by electrochemical reduction of a number of 4-nitrophenyl diphenylphosphinates have been examined by e.s.r. spectroscopy and hyperconjugation invoked to explain the observed coupling of phosphorus 17a3b

l4 l5

l7

l9 2o

A. Begum, A. R. Lyons, and M. C. R. Symons, J . Chem. Sac. (A)., 1971, 2388. A. R. Lyons and M. C. R. Symons, Chem. Comm., 1971, 1068. M. C. R. Symons, Tetrahedron Letters, 1971, 4919. (a) A. Begum and M. C. R. Symons, J. Chem. SOC.(A), 1971,2065; (b) C. M. L. Kerr and F. Williams, J. Phys. Chem., 1971, 75, 3023. D. Kilcast and C. Thomson, Tetrahedron, 1971, 27, 5705. E. H. Braye, I. Caplier, and R. Saussez, Tetrahedron, 1971, 27, 5523. C. Thomson and D. Kilcast, Chem. Comm.,1971, 782.

240

Organophosphorus Chemistry

to the radical centre.21 A further examination of the e.s.r. spectrum of the radical (8) has shown that there is considerable delocalization of the odd electron over the biphenyl system.22

(8)

Irradiation of hexamethylphosphoric triamide in the presence of oxygen leads to a hydroperoxide derived by hydrogen abstraction from a methyl group.23 This same radical was reported last year as being formed electrochemically from the amide (Vol. 3, p. 234). Further products [e.g. (9)] have been isolated from the oxidation of phosphabenzenes by mercuric acetate in the presence of aqueous Replacement of the alcohols by amines has lead to a synthesis of several interesting quinquecovalent compounds [e.g. (10) 1.

iL

P11

L5

Hs(OAc),,

P 11

+.

Ph

/ /

Ph

,

P 11

2% PI1

KOH

PI1

PI1

/P.

Ph

P 11

/4g2jL

P 11

,pi.

PI1

2+ Ph

/ /

fi

Ph

RO OAc P I1

P11

I

1

(9) 21

za 23

W. M. Gulick, J. Amer. Chem. SOC.,1972, 94, 29. R. Rothuis, T. K. J. Luderer, and H. M. Buck, Rec. Trav. chim., 1972, 91, 836. J.-Y. Gal and T. Yvernault, Bull. SOC.chim France, 1972, 839. A. Hettche and K. Dimroth, Tetrahedron Letters, 1972, 829.

Radical, Photochemical, and Deoxygenation Reactions 241 Further evidence has been presented for the reaction of triarylphosphines with 7,7,8,8-tetracyanoquinodimethaneas involving a phosphinium A very short review has appeared on the use of radical reactions in the synthesis of heterocyclic phosphorus compounds.26 On the basis of products formed in trapping experiments, the dechlorination of phenylphosphonothioic dichloride by magnesium is thought to result in the formation of a phosphinidene sulphide (11).27 PhPSCI,

- Mg

EtJ,

PhPS

PhP(S)(SEt),

MPh

Ph

0 0 ‘P’ / \ PI1 s

/

P-s

Ph

It has been previously suggested that Grignard reagents dechlorinate the acid chloride in a similar way (see Vol. 1, p. 259). The heating of pentaphenylcyclopentaphosphine in the presence of biphenylene at high temperatures gives 9-phenyl-9-phosphafluorene and phenylphosphinidene was suggested as being an intermediate.28 Phosphines have been used to trap sulphenes produced by dehydrochlorination of methanesulphonyl chlorides.2s The reaction of tetrazolopyridine with triphenylphosphine to give an iminophosphorane was shown, by kinetic measurements, not to involve a nitrene intermediate, but rather to involve reaction of the phosphine with the azide (12).30a The reaction

CI

Iy \ N

N=&

26 27 28

2s

3

Q,N3%

CI (12)

CI

I

N=N- N =PPh:,

M. P. Naan, R. L. Powell, and C. D. Hall, J. Chem. SOC.(B), 1971, 1683. D. Redmore, Chem. Reu., 1971, 71, 315. S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, Chem. Comm., 1971, 1186 A. Ecker and U. Schmidt, Monatsh., 1971, 102, 1851. J. F. King, E. G. Lewars, and L. J. Danks, Canad. J. Chem., 1972,50, 866. (a) T. Sasaki, K. Kanematsu, and M. Murata, Tetrahedron, 1971, 27, 5359; (6) L. J. Leyshon and D. G. Saunders, Chem. Comm., 1971, 1608.

242

Organophosphorus Chemistry

of o-azidophenyl acetate with triethyl phosphite to give phosphorimidates, which subsequently cyclize to give benzoxazoles (Scheme 5), may occur by a If this is the case, it would explain why the reaction similar of o-nitrophenyl acetate with triethyl phosphite, which probably involves a

+ (EtO),PO Scheme 5

nitrene or nitrene precursor, produces the phosphorimidate much less efficiently. Further examples have been reported of the reactions of diazomethylphosphonates with ole fin^.^' Pyrazolineshave been isolated from the reaction of diazomethylphosphonates with norbornene and norbornadiene. Direct photolysis of the pyrazoline (1 3 ; R = Ph) produced the cyclopropylphos-

n

P ( :0 )(0Me).,

Me

P(:O)(OMe),

81

H. J. Callot and C. Benezra, Cannd. J. Chew., 1972, 50, 1078.

Radical, Photochemical, and Deoxygenation Reactions

243

phonate (1 4), whereas triplet-sensitized decomposition gave compounds (14) and (15). In the former case, the singlet biradical formed by extrusion of nitrogen can ring-close before bond rotation can take place. Sensitized decomposition produces a triplet biradical which cannot undergo ring-closure until intersystem crossing takes place, and consequently bond rotation takes place before ring-closure. Photolysis of (16) results in expulsion of trimethyl phosphate and the formation of a reactive intermediate (probably a nitrile ylide), which can be trapped by alkenes and a l k y n e ~ . ~ ~ COLMe I

F&>( N-\ 11v F K ,P
R

Photolysis of bis(diphenylphosphiny1) peroxide (17) has been shown, by means of oxygen labelling, to result in 0-0 bond h o r n ~ l y s i s . In ~~~ contrast, this compound undergoes thermal rearrangement by either a concerted process or via an intimate i ~ n - p a i r . ~ ~ ~ ~ ~ Ph,POOPPh, II II o* 0" (17)

o*=O'R

-----+ PhzP-0' II IIV

\

O*

II r/o\l/Ph PhzP-0-P, + 7 1 * Ph -0

-

*

Ph

I

*

Ph,P -0- P-OPh II II o* 0" Ph

---+ Ph2P-O-P I1 0"

I

II

-0Ph

0"

The mechanism by which phosphates, e.g. the disodium salts of glycerol1-phosphate and glycerol-2-phosphate, undergo photoinduced hydrolysis

has been the subject of a careful The mechanism of the primary photochemical processes still remains a mystery. 32 33

s4

K. Burger and J. Fehn, Tetrahedron Letters, 1972, 1263, ( a) R. L. Dannley, R. L. Waller, R. V. Hoffman, and R. F. Hudson, J. Org. Chem., 1972, 37, 418; (b) R. L. Dannley, R. L. Waller, R. V. Hoffman, and R. F. Hudson,

Chem. Comm., 1971, 1362. J. Greenwald and M. Halmann, J. C.S. Perkin 11, 1972, 1095.

244

Organophosphorus Chemistry

Photolysis of 1,2-diphenylbut-l-ene-3,4-dione in the presence of trimethyl phosphite produces the phosphonate (19) and the reaction can be visualized as occurring via the radical (18).35 The dione also reacts with the phosphite in a thermal reaction to give (19) and (20).

r'llny pllFo 0

PI1

(MeO),P

/I u

d

(MeO), P*=O (18)

PI1

P (OMe),

4

0

Ph (19) -I-

Ph

(19)

)q:Me P(OMe),

d

(20)

Recently, there has been an interest shown in the way that hetero-atoms (e.g. nitrogen) interact with singlet oxygen.36a The finding that the phosphorin (21) undergoes an addition reaction with this species 36b is therefore

I

0 \OR

t /- \

Me0

OMe

M e 0 OMe

(22) 35 s8

P. R. Ortiz de Montellano and P. C. Thorstenson, Tetrahedron Letters, 1972, 787. (a)For some leading references see 1. B. C. Matheson and J. Lee, J . Amer. Chem. SOC., 1972, 94, 3310; K. Dimroth, A. Chatzidakis, and 0. Schaffer, Angew. Chem. Internat. Edn., 1972, 11, 506.

Radical, Photochemical, and Deoxygenation Reactions

245

particularly significant. When the phosphorin (22) is used, cycloaddition to the ring occurs. The rather surprising observation has been made that gemacrene gives totally different products when it reacts with singlet oxygen, generated in a photosensitization reaction, than when it reacts with the triphenylphosphite-ozone a d d ~ c t . ~There ' does not seem to be a clear-cut rationalization of this odd behaviour. 2 Deoxygenation and Desulphurization Reactions Alkylidenephosphoranes (23) react with t-butyl hydroperoxide to give an adduct which subsequently undergoes homolytic cleavage of the 0- 0 Ph,P=CR'R2 (23)

+ Bu'OOH

__f

Bu'O.

Ph:,P-CHR'R2 I O-OBut

+

Ph3PCHR*R2 I 0.

I

hydrogen abstraction

Ph,PO

+

+ - - - - I

R1R2CH2

Ph,PCHR1R2

OH

bond.38 Kinetic measurements have shown that several alkyl hydroperoxides are deoxygenated by tervalent phosphorus compounds via an ionic and not a radical m e c h a n i ~ r n . ~ Malonyl ~ peroxides (24)40 and 18peroxylactones 41 are also deoxygenated by triphenylphosphine by an ionic mechanism. Further quinquecovalent phosphorus compounds have been prepared by the addition of dialkyl peroxides to p h o ~ p h i n e s .In ~ ~the case 0

37

38 yn

40 41 42

T. W. Sam and J. K. Sutherland, J . C . S . Chem. Comm., 1972, 424. K. Yamada, K. Akiba, and N. Inamoto, Brcll. Chem. Soc. Japan, 1971, 44,2437. R. Hiatt, R. J. Smythe, and C . McColeman, Canad. J. Chem., 1971, 49, 1707; R. Hiatt and C. McColeman, ibid., p. 1712. W. Adam and J. W. Diehl, J . C . S. Chem. Comm., 1972, 797. W. Adam and C. Wilkerson, Chem. Cornm., 1971, 1569. D. B. Denney, D. Z . Denney, C. D. Hall, and K. L. Marsi, J . Amer. Chem. SOC., 1972, 94, 245.

9

246

Organophosphorus Chemistry

of reaction with bis(trifluoromethy1) peroxide, fluorine abstraction occurred with the result that difluorophosphoranes were There have been several synthetic procedures developed for the preparation of alkyl chlorides,44amides 45 (including peptides 46), anhydride^,^^ vinyl halides,47and the alkylation of amines 48 in which the initial reaction is that of triphenylphosphine with carbon tetrachloride. The stereochemical requirements of this reaction have been the subject of a The oxidation of diphenylphosphine by peroxybenzoic acid was shown to occur by an ionic m e c h a n i ~ r n . ~ ~ A convenient synthesis of sulphenyl chlorides has been developed in which a thiol is reacted with chlorocarbonylsulphenyl chloride and the resulting adduct desulphurized by triphenylpho~phine.~~ Further examples 52$ 53 have been enumerated in which olefins are stereospecifically synthesized by a two-fold extrusion process, one of which is the removal of sulphur by a phosphine, e.g. in the synthesis of bicyclobutylidene (25).

The desulphurization of thionocarbonates by phosphines has also been used in a stereospecific olefin synthesis.64 Of the several applications of the desulphurization of d i s ~ l p h i d e s , ~ ~ - ~ ~ that of alkyl ally1 disulphides 67 seems particularly interesting. From the evidence cited it would seem that these disulphides readily rearrange to thiosulphoxides (26) which are desulphurized by the phosphine. The rate enhancement caused by increasing the size of the substituents R2and R3 43 44 45

46

47 48 40

50

51 52

53

54 56

56

67

N. J. De’Ath, D. Z . Denney, and D. B. Denney, J. C. S . Chem. Comm., 1972, 272. B. Castro and C. Selve, Bull. Sac. chim. France, 1971, 2296. B. Castro and J.-R.Dormoy, Bull. SOC.chim. France, 1971, 3034. S. Yamada and Y. Takeuchi, Tetrahedron Letters, 1971, 3595; T . Wieland and A. Seeliger, Chem. Ber., 1971, 104, 3992. N. S. Isaacs and D. Kirkpatrick, J. C. S. Chem. Comm., 1972, 443. B. Castro and C. Selve, Bull. SOC.chim. France, 1971, 4368. R. Aneja and A. P. Davies, J . C . S. Chem. Comm., 1972, 722. R. Curci and F. Di Furia, Tetrahedron, 1971, 27, 4601. D. L. J. Clive and C . V. Denyer, J . C. S. Chem. Comm., 1972, 773. J. W. Everett and P. J. Garratt, J. C . S. Chem. Comm., 1972, 642. D. H. R. Barton and B. J. Willis, J. C. S. Perkin I, 1972, 305. T. M. Dawson, J. Dixon, P. S. Littlewood, B. Lythgoe, and A. K. Saksena, J . Chem. SOC.( C ) , 1971, 2960. D. H. R. Barton, P. G. Sammes, M. V. Taylor, C. M. Cooper, G . Hewitt, B. E. Looker, and W. G. E. Underwood, Chem. Comm., 1971, 1137. T. Mukaiyama and M. Hashimoto, Bull. Chem. SOC.Japan, 1971,44,2284. G. Hofle and J. E. Baldwin, J. Amer. Chem. SOC.,1971,93,6307.

Radical, Photochemical, and Deoxygenation Reactions

247

R2 R3

(26)

was rationalized as being due to the rearrangement relieving some of the strain in the starting disulphides. In a study of the deoxygenation of sulphoxides it was found that the reaction is favoured by increasing the basicity of the tervalent phosphorus compound. With some phosphites a Michaelis-Arbuzov reaction was found to compete,58e.g. in the reaction of the phosphite (27) with methyl

(MeO),POPh

(27)

+ PhSMe II

0

-c

(MeO),POPh II

+

PhSMe

0

MeP(0Me) (OPh)

II

+ PhSMe

0

II

0

phenyl sulphoxide. 00-Diethyl phosphorothiolothionic acid is effective in deoxygenating sulphoxides as well as N - o ~ i d e s . This ~ ~ reagent also regenerates sulphides from sulphilimines and sulphonium ylides. Phosphine oxides were unreactive. A further example of the deoxygenation of a nitrile oxide (generated by thermolysis of a 1,2,5-oxadiazole) to give a nitrile has been reported.60 Several alkyl nitroso-compounds, e.g. (28), are deoxygenated by phosphites, and nitrenes are suggested as being precursors of the reaction products.61 Nitrocyclopropanes [e.g. (29) and (30)] have been found to undergo some interesting rearrangement reactions on deoxygenation, and in the case of

68

6o

S. Oae, A. Nakanishi, and S. Kozuka, Tetrahedron, 1972, 28, 549. S. Oae, A. Nakanishi, and N. Tsujimoto, Tetrahedron, 1972, 28, 2981. S. M. Katman and J. Moffat, J . Org. Chem., 1972, 37, 1842. B. Sklarz and M. K. Sultan, Tetrahedron Letters, 1972, 1319.

=Q--Organophosphorus Chemistry

248

&?

0,N

O=N

(RO),P+-O P?

(29)

I

(30) there is complete removal of nitrogen.62 Further details have been published of the deoxygenation of 2-nitrophenyl phenyl sulphides in which the phenyl ring bears substituents in the ortho positions.63 In the case of

0,N’

Ph

(PriO)3P-O-

N’

3 0

Ph

h

I’ll

the dimethyl compound (32) the reaction took a rather unexpected course and gave the aminotetroxyphosphorane (33).g4 The nitrodiphenylmethane (34) gave the products (35) and (36), which can be visualized as being produced from a nitrene or a nitrene precursor. 62

63 64

S. Ranganathan and C. S. Panda, Tetrahedron Letters, 1971, 3841. J. I. G. Cadogan and S. Kulik, J. Chem. SOC.(0, 1971, 2621. J. I. G . Cadogan, D. S. B. Grace, P. K. Lim, and B. S. Tait, J. C. 5’. Chem. Comm., 1972, 520.

Q&=J+ 249

Radical, Photochemical, and Deoxygenation Reactions ( MeO), P : (MeO),P,

NO, Me

Me

I

Ar

Ar

(33)

(34)

\

I

11

Physical Methods BY J.

C. TEBBY

The abbreviations PIv, and Pv refer to the co-ordination number of phosphorus, and the compounds in each subsection are dealt with in this order. A number of relevant theoretical studies are included in this chapter. In the formulae the letter R will represent hydrogen, alkyl, or aryl, X will represent electronegative substituents, and Y and Z will be used when a wide variety of substituents is indicated. 1 Nuclear Magnetic Resonance Spectroscopy Positive 3lP chemical shifts (6p) are upfield from 85% phosphoric acid.

Chemical Shifts and Shielding Effects.-First it is necessary to bring to your attention the recent suggestions that a scale with chemical shifts positive to increasing frequency should be adopted. Adoption of this suggestion, which is fully discussed in the Specialist Periodical Reports on n.m.r. (Vol. 1),l would mean a reversal of the signs presently used for SP. Clearly it is now very important for authors using any 8 scale to state whether positive shifts are upfield or downfield of the reference signal.

Sp. There has been a marked increase in the use of 31P n.m.r. spectroscopy. The improvements in instrumentation, such as for Fourier transform,2 have increased the scope of this aspect of n.m.r. considerably. Thus there has been a marked advance in the study of phosphoruscontaining natural products. It is now possible to show that in solution (1) predominates (ca. 90%) over its cis-isomer (p-furanose), with negligible amounts of the open-chain forms. Also, well-structured 31Pn.m.r. spectra

'Nuclear Magnetic Resonance', ed. R. K. Harris (Specialist Periodical Reports), The Chemical Society, London, 1971, Vol. 1. R. J. Cushley, D. R. Anderson, and S. R. Lipsky, Analyt. Chem., 1971, 43, 1281. G. R. Gray, Biochemistry, 1971, 10, 4705.

250

25 1

Physical Methods

of two purified transfer RNAs have been ~ b t a i n e dand , ~ discrete peaks in the phosphonate and phosphate regions of the spectra of hydrolysates from the sea anemone are reported.6 Although 31P N.m.r. has been used to study the structure of the signals are necessarily broad, quite accurate estimates of 8p have been obtained, e.g. solid tetrabutylphosphonium iodide has Sp - 35.1 p.p.m., which may be compared with -32 p.p.m. for a solution. There are many examples8 of shielding of the phosphorus nucleus caused by the introduction of electronegative groups on a substituent which may T-bond with the phosphorus atom. A recent example concerned the phosphonates (2).9 This has usually been attributed to an increase in

d,-p, bonding produced by the inductive withdrawal of electrons. However, it must be pointed out that according to the quantum-mechanical treatment developed by Letcher and Van Wazer,loa the introduction of electronegative substituents at phosphorus will cause shielding by a a-bond effect but not by a d,-p, bonding effect. In fact, deshielding is predicted for increased occupation of d-orbitals. This latter effect can be envisaged as being due to increased disturbance of the symmetrical electron distribution around the phosphorus atom with a resultant increase of the paramagnetic effect. Experimental evidence in support of this rationalization is obtained from the downfield position of PS43-, P043-,and $(NR,), compared with the shifts estimated for these groups from the a contribution only. Further support is obtained from the upfield shifts of 8p for the salts (3) and (4) as the electronegativity of X increases.llP l2

(3)

a

’

lo

l1

l2

M . Gueron, F.E.B.S. Letters, 1971, 19, 264. T. 0.Henderson, T. Glonek, R. L. Hilderbrand, and T. C. Myers, Arch. Biochem. Biophys., 1972, 149, 484. K. B. Dillon and T. C. Waddington, Spectrochim. Acta, 1971, 27A, 1381. K. B. Dillon and P.N. Gates, J.C.S. Chem. Comm., 1972, 348. ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London (a) 1970, Vol. 1, Chap. 11; (b) 1971, Vol. 2, Chap.11; (c) 1972, Vol. 3, Chap. 11. C. C. Mitsch, L. D. Freedman, and C. G. Moreland, J . Magn. Resonance, 1971,5, 140. J. H. Letcher and 5. R. Van Wazer, ‘Topics in Phosphorus Chemistry’, Wiley, New York, 1967, Vol. 5 , (a) p. 75; (6) p. 227. D. W. Allen, B. G. Hutley, and M. T. J. Mellor, J.C.S. Perkin IZ, 1972, 63. D. W. Allen and B. G. Hutley, J.C.S. Perkin 11, 1972, 67.

Organophosphorus Chemistry

252

However, there are observations which do not appear to be explained by this theory. For instance, in comparison with a phosphonium salt, the phosphonium ylide possesses considerable d,-p, bonding and has a less electronegative carbon atom bonded to phosphorus. It is predicted that both of these effects should deshield the phosphorus nucleus, which is contrary to the experimental observations. Further, when the carbanion of the ylide is delocalized (which may be achieved with a minimal change in inductive effect), 8p is shifted downfield, and when alkyl groups are introduced on the a-carbon atom of ylides, 8p is shifted upfield. Note that the alkyl groups would be expected to increase the + I effect and the M effect by way of increased p-character of the lone pair of electrons. Similar conclusions may be drawn from a comparison of ylides with phosphine oxides. Calculations of d,-p, bonding in ylides have been based on HMO theory.13 It is claimed that they interpret qualitatively the experimentally measured charge distribution in the ground state. The bond angle of PrI1and PIv compounds is specified l4 to be a suitable parameter for explaining Sp if the appropriate co-ordination number and number of phosphorus electrons are assigned and if a proper discernment between positive and negative values of nuclear magnetic shielding is made. Hyperconjugation is believed to prevent too large a charge developing between bonded atoms.14 Values of Sp for phosphorus halides have been calculated15 to within & 5 p.p.m. of their observed values. The results also suggest that the C1 > I > F in PIII compounds is anomalous order of the shielding Br a consequence of an inductive effect modified by geminal delocalization between halide substituents l5 rather than the operation of a r-bonding effect.16 The calculations were based on the assumption that the paramagnetic term is dominant and controlled by changes in the ionic character of the phosphorus bonds. PrI1 Compounds. A plot of 8p for a series of diphenylphosphines (R-PPPh,) versus a,,, of R-13CH3 follows a steady curve, which shows that the factors affecting the cheniical shifts are closely related. The point for triphenylphosphine, i.e. R = phenyl, falls on the same line as for alkyl groups. It is suggested that this rules out a d,,-p, intera~ti0n.l~ However, the conclusion ought to be that there is no significant change in any d,--pn bonding upon introducing a third phenyl group. Values of 8p for diphenylalkylphosphines (5 ; Y = H) are virtually unaffected when hydrogen is replaced by a second diphenylphosphino-group (5; Y = PPh2) provided the phosphino-groups are separated by one or more methylene groups.l* The effect of directly bonded diphenylphosphino-groups is not

+

N

l3

l4

l5 l6 17

18

H. Goetz and F. Marschner, Tetrahedron, 1971, 27, 1669, 3581. D. Purdela, J. Magn. Resonance, 1971, 5 , 23. L. Phillips and V. Wray, J.C.S. Perkin II, 1972, 214. J. W. Emsley, J. Feeney, and L. H. Sutcliffe, 'High Resolution Nuclear Magnetic Resonance Spectroscopy', Pergamon Press, Oxford, 1966, Vol. 2, p. 1055. B. E. Mann, J.C.S. Perkin II, 1972, 30. H. G . Horn and K. Sommer, Spectrochirn. Acta, 1971, 27A, 1049.

25 3

Physical Methods

normally so different from that of a phenyl group; however, the cyclic tetraphosphine (6) has Sp - 34.6 p.p.m.ls Protonation of tetramethyldiphosphine leads to considerably less deshielding than for dimethylphosphine.20 The effect of heavy atoms such as silicon, germanium, and tin on phosphorus is to produce a large shielding effect. The application of the theory of Letcher and Van Wazer did not give a satisfactory explanation for the shifts.21 The influence of substitution on 8p of the 23 The cyclic delocalization of the lone phospholes (7) has been studied.22* pair of electrons on phosphorus is interpreted within the Letcher-Van Wazer formalism.22 Mixed halides of methylphosphines, e.g. (8), have chemical shifts between those of the appropriate d i h a l i d e ~ .Likewise ~~ 6p X

UY Me-P,

I

R

/

F

Br

MeO-P,

/CF,

Me

y, Z/p-C-N

(9)

of - 118.8 p.p.m. for the mixed methoxyphosphines (9) is intermediate between the chemical shifts - 124 and - 94.8 p.p.m. of the dimethyland bis(trifluoromethyl)-methoxyphosphines.25 The phosphorus atom in PC=N compounds (10) is in the shielding region of the nitrile group. Consequently replacement of a range of P-substituents, such as methyl, phenyl, and methoxy- and dimethylamino-groups, always produces a shielding effect. The amount of shielding tends to increase with the number of nitrile groups already present.26 The effect was very small in one case: the replacement of a methyl group in trimethylphosphine (Sp rose from 62.0 to 62.6 p.p.m.).26 Cyanodimethylphosphine (10; Y = Z = Me) is probably one of the most polarized cyanophosphines (p. 274 of ref. 8c), and therefore pn-pn bonding may be having a compensating deshielding effect.

+

lS 2o 21 22

23 24 25

36

+

M. Baudler, J. Vesper, P. Junkes, and H. Sandmann, Angew. Chem., Internat. Edn., 1971, 10, 940. F. Seel and K. D. Velleman, Chem. Ber., 1971, 104, 2967. G. Engelhardt, 2. anorg. Chem., 1972, 387, 52. F. Mathey and R. Mankowski-Faveli, Org. Magn. Resonance, 1972, 4: 171. L. D. Quin and S. G. Borleske, Tetrahedron Letters, 1972, 299. H. W. Schiller and R. W. Rudolph, Inorg. Chern., 1972, 11, 187. F. Seel and K. D. Velleman, Chem. Ber., 1972, 105, 406. C. E. Jones and K. J. Coskran, Inorg. Chem., 1971, 10, 1536.

254

Organophosphorus Chemistry

PIv Compounds. Estimations of the degree of protonation of phosphine oxides vary, depending on whether conclusions are drawn from lH. n,m.r. or 31P n.m.r. spectra. A comparison of six oxides indicates that 8p reflects , depends also on the direct protonation to a greater extent than 8 ~which state of the molecule as a A comparison of the shielding effects of oxides and sulphides (1 1; X = 0 or S) showed that the deshielding

(1 1)

effect of the sulphide atom is least when the phosphorus atom bears alkyl groups and most when it bears alkoxy-groups. A change in the structure of the alkyl groups had the usual effect, i.e. a decrease in the number of hydrogens on the a-carbon atom led to deshielding.2s A claim for a linear correlation of 8p with the phosphorus 2pelectron binding energies for a series of triphenylphosphonium salts2Bis not convincing. A study of the effects of cyclization on 8p of phosphites, phosphates, and related compounds has shown that the formation of a six-membered ring causes shielding of the phosphorus nucleus for both PI1*and PIv compounds in accordance with a a-bonding effect of steric origin. A five-membered ring also causes shielding for the PI'' compounds, but the PIv compounds are deshielded in accordance with the onset of a stereoelectronic effect such as p,-& bonding.30 The cyano and ethoxycarbonyl derivatives of the 2-troponyl ylide (12; Y = CN or C0,Et) possess 8p -6.8 and Y

+ 66.9 p.p.m., respectively. X-Ray diffraction shows that the ester has much more Pv character than the nit~-ile.~l Pv Compounds. Further triphenyloxyphosphoranes (1 3) have been prepared. The range of chemical shifts are + 52 k 9 ~ . p . m . 33 ~ ~The s effect of cyclization has been studied for tetra- and penta-oxyphosphoranes. The formation of one six-membered ring, as in (14; It = l), and the 28

so 31

32

33

N. K. Skvortsov, A. V. Dogadina, G. F. Tereshchenko, N. V. Morkovin, B. I. Ionin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2839. I. L. Knunyants, V. I. Georgiev, I. V. Galakhov, L. I. Ragulin, and A. A. Neimysheva, Doklady Chem., 1971, 201, 992. W. E. Swartz, jun., and D. M. Hercules, Analyt. Chem., 1971, 43, 1066. G. M. Blackburn, J. S. Cohen, and I. Weatherall, Tetrahedron, 1971, 27, 2903. 1. Kawamoto, T. Hata, Y . Kishida, and C. Tamura, Tetrahedron Letters, 1972, 1611. E. E. Schweizer and W. S. Creasy, J. Org. Chem., 1971, 36, 2244. C. F. Garbers, J. S. Malherbe, and D. F. Schneider, Tetrahedron Letters, 1972, 1421.

255

Physical Methods

(15)

(16)

formation of two six-membered rings, as in (15; n = l), produces consecutive small downfield shifts of up to 4 p.p.m. whereas the formation of one five-membered ring, as in (14; n = 0), and the formation of two fivemembered rings, as in (15; n = 0), produces consecutive large downfield shifts of 17-23 p.p.m. The 8p of + 8 for (15; n = 0) was the lowest of the series.34 It is now possible to make a comparison between the shielding effect of oxygen and sulphur in Pv compounds. It has been found that values of 8p for (16) and for mixed sulphur-oxygen phosphoranes are in the region 0 f 30 p.p.m.lobS36 whereas oxyphosphoranes have shifts in the 36 * Thus the sulphur atom has a marked range +40 f 3 0 ~ . p . m . ~ ~ deshielding effect relative to oxygen, as it does in PIv compounds.1ob Isotope eflects. Deuterium substitution in PH compounds increases the shielding of the phosphorus nucleus. PII1Compounds are changed to a greater extent than PIv compounds and roughly in proportion to the number of protons replaced.37 Deuterium substitution in dialkyl phosphonates (17) shifts 8p by 0.4 p.p.m. upfield, which is commensurate with a decrease of the OPO bond angle of ca, 339

&. The 13C chemical shift ( 8 ~ )for the cis- and trans-vinylphosphines (18) and (19) shows that the P1lr atom deshields both ethylenic carbon atoms. The same trends were observed for the carbon and proton chemical shifts, which suggests that local charge density and not magnetic anisotropy 8p

aa 97 88

B. C. Chang, W. E. Conrod, D. B. Denney, D. Z . Denney, R. Edelman, R. L. Powell, and D. W. White, J. Amer. Chem. Soc., 1971,93,4004. N. J. De'Ath and D. B. Denney, J.C.S. Chem. Comm., 1972, 395. Ref. 8c, p. 257. A. A. Borisenko, N. M. Sergeyev, and Y . A. Ustynyuk, Mol. Phys., 1971, 22, 715. W. J. Stec, N. Goddard, and J. R. Van Wazer, J. Phys. Chem., 1971, 75, 3547.

256

Organophosphorus Chemistry

dominates the hi el ding.,^ The PII1atom of the tris-heteroarylphosphines (20) shifts 6~ downfield for all the carbon The shifts are larger for PIv atoms. The crowding of the methyl and R groups in 3-phospholens, e.g. (21), causes shielding of the carbon nucleus of the methyl group. In fact, relief of this crowding by conversion of the cis-isomer (21) into the corresponding trans-isomer causes a larger downfield shift than its conA 13C n.m.r. study of a wide range of diethyl version into the Y8,

,c=c, 14

(20)

,But

H

(21)

y2p,

,c=c, H

/H Ph

(22)

phosphonate compounds (22) indicates a constant additive effect of -13.2p.p.m. to aC upon replacing a proton in 13CH3Y with the (EtO),P( 0) groups.42 31P and 13C n.m.r. spectroscopy have been used to study the structure of nicotinamide adenine dinucleotide and related compounds in their reduced and oxidized forms. It was concluded that there is an electrostatic interaction between the phosphoryl oxygen in the diphosphate backbone and the quaternary nitrogen of the pyridine ring.43 6 ~ The . PH doublet of the cyclic phosphine (23) in CFCl, at -50 "C disappears when the temperature is raised to +25 "C. Water causes the signal to reappear as a singlet.44 Unlike vinylphosphines and vinylp h o ~ p h o n a t e sthe , ~ ~assignment of the stereochemistry of vinyl phosphates is not assisted by a vicinal coupling constant, and therefore it is necessary to rely on shielding effects. Assignments have been made for the phosphates (24; R = HAor Ph, Y = Hc, Ph, alkyl, C1, or Br) based on the

38

41 42 43 44

46

M. P. Simonnin, R. M. Lequan, and F. W. Wehrli, Tetrahedron Letters, 1972, 1559. H. J. Jakobsen and 0. Manscher, Actu Chem. Scand., 1971, 25, 680. J. J. Breen, S. I. Featherman, L. D. Quin, and R. C. Stocks,J.C.S. Chem. Comnz., 1972, 657. G. A. Gray, J. Amer. Chem. Soc., 1971, 93, 2132. M. Blumenstein and M. A. Raftery, Biochemistry, 1972, 11, 1643. J. B. Lambert and W. L. Oliver, Tetrahedron, 1971, 27, 4245. V. V. Kosovtsev, T. N. Timofeeva, B. I. Ionin, and V. N. Chistokletov, J . Gen. Chem. (U.S.S.R.), 1971, 41, 2671.

257

Physical Methods

known electron-donating property of the phosphate group, which shields Hc more than Hg. The addition of boron trifluoride nullifies this property. In fact it will reverse the shielding effect if an a-phenyl group is present. The shielding constants for the dialkyl phosphate group have been calculated from the chemical shift data; they are - 1.42, geminal; +0.30, cis; and +0.50, trans (to be used with -5.27 as the base value for ethylene).4s The lH n.m.r. spectra of the allylic ylides (25; R = Me R

H

/

'HA

/

d (25b)

(25a)

or H) are in accordance with a very strong deshielding effect on the a-proton, HA, when it is close to the oxygen anion. Thus HA of (25a; R = Me) appears at T 4.42 compared with T 7.1 1 for H ~ i n ( 2 5 bR ; = Me).47 Studies of Equilibria, Reactions, and Solvent Effects.-Lanthanide shift reagents have been found to be effective for phosphines 48 and phosphoryl c o r n p o ~ n d s6o, ~but ~ ~ not for thiophosphoryl c o m p o ~ n d s . 61 ~ * In ~ a comparison of various shift reagents, europium nitrate hexadeuterium oxide (26) was found to give large shifts of 8~ for phosphates and phosphonates. A contact contribution to the 8p shifts was e ~ t a b l i s h e d .When ~ ~ there are two possible sites for co-ordination, as in the aminophosphine (27), steric effects play an important role. Co-ordination occurs at nitrogen in (27; R = H) but at phosphorus in (27; R = Me).48 The n.m.r. parameters 0

H 0 II Ph-P -CH2Ph I

48

47 49

6o

H MeJ&Ms Me

Me It

I. J. Borowitz, S. Firstenberg, E. W. R. Casper, and R. K. Crouch, J . Org. Chem., 1971, 36, 3282. R. K. Howe, J. Amer. Chem. Soc., 1971, 93, 3457. R. C. Taylor and D. B. Walters, Tetrahedron Letters, 1972, 63. J. K. M. Sanders and D. H. Williams, Tetrahedron Letters, 1971, 2813. T. M. Ward, I. L. Allcox, and G . H. Wahl, Tetrahedron Letters, 1971, 4421. K. C. Yee and W. G. Bentrude, Tetrahedron Letters, 1971, 2775.

25 8 Organophosphorus Chemistry obtained using a europium shift reagent with (28) compared favourably with those obtained by the LAOCN analysis of the ordinary second-order Eu(dpm), also developed the non-equivalence of the methylene protons of (29) 5 2 and assisted in the structural studies of the cyclic phosphine oxides (30)53and (31).64 Pr(dpm), was less effective since the shifts must cross over before a good separation is ~ b t a i n e d . ~ , A linear correlation is reported 55 between Gp(phosphine) and the change in chemical shift that occurs upon co-ordination of tertiary phosphines with a number of transition metals. The half-neutralization potential, the Taft o*, and 8p of the complexes of tertiary phosphines and titanium tetrachloride have been found to be related.5s The equilibria involving the co-ordination of phosphoryl compounds and water with metal ions such as A13+are sufficiently slow to be studied by lH n.m.r. and 31Pn.m.r. spectroscopy. Discrete signals from co-ordinated and unco-ordinated ligands are Where this does not occur the equilibrium constant can be estimated from a plot involving chemical shift and concentration of Mono-, di-, and tri-alkyl phosphates have very similar B p values. Separation of the signals may be achieved by the addition of di-(Zethylhe~y1)amine.~~ The methoxide phosphonium salts (32) l1 and (33) have

been shown to be in equilibrium with their Pv oxyphosphoranes, whereas the quasiphosphonium chlorides, bromides, and iodides (34) are not.s1 Many fluoro-oxyphosphoranes, e.g. (35) and (36), are in the Pv form,62

6*

G. P. Schiemenz and H. Rast, Tetrahedron Letters, 1971, 4685. B. D. Cuddy, K. Treon, and B. J. Walker, Tetrahedron Letters, 1971, 4433. J. R. Corfield and S. Trippett, Chem. Comm., 1971, 721. B. E. Mann, C. Masters, B. L. Shaw, R. M. Slade, and R. E. Stainbank, Znorg. Nuclear Chem. Letters, 1971, 7 , 881. F. Calderazzo, S. A. Losi, and B. P. Susz, Helo. Chim. Acta, 1971, 54, 1156. J. J. Delpuech, A. Peguy, and M. R. Khaddar, J. Magn. Resonance, 1972, 6, 325; J. Crea and S. F. Lincoln, Znorg. Chem., 1972, 11, 1131. S. V. Zenin, A. P. Osipov, V. A. Polyakov, and G. B. Sergeev, Russ. J. Phys. Chem.,

58

S. Oshima, K. Asano, T. Nishishita, H. Tsuji, and H. Yokogawa, J. Japan Petrol Inst.,

62

63 64 66

66

67

1971, 45, 867.

6o

61 62

1971, 14, 499. H. Schmidbaur and H. Stuhler, Angew. Chem. Znternat. Edn., 1972, 11, 145. L. V. Nesterov, R. I. Mutalapova, S. G. Salikhov, and E. I. Loginova, Bull. Acad. Sci. U.S.S.R., 1971, 346. S. C. Peake, M. Fild, M. J. C. Hewson, and R. Schmutzler, Znorg. Chem., 1971, 10, 2723.

Physical Methods

259

but the volatility and absence of PF coupling in the tetra-alkyl- and tetraaryl-fluorophosphoranes suggest that these compounds exist as rapidly interconverting mixtures of PIv and Pv species.63

Pseudorotation.-LCAO-MO calculations on the hypothetical molecule PH5 confirm (a) that the trigonal bipyramid (t.b.p.) is the most stable configuration, (b) that the apical orbitals of the t.b.p. are more electropositive than the radial orbitals, (c) that there would be an equilibrium of t.b.p. structures, but those with the most electronegative groups in apical orientations will be more stable and predominate extensively over other t.b.p. configurations, and ( d ) that the lowest fundamental frequency of a t.b.p. corresponds to the equatorial in-plane bending motion as shown in (37), the force constants being nearly four times smaller than those of the

apical bending motion.64 EHMO calculations on the hypothetical molecules HnPFb-n indicate that r-acceptors prefer apical sites of the t.b.p. structure and n-donors prefer radial Pentafluorophosphorane has also been examined separately using LCAO-MO calculations.66 A system of nomenclature, useful for intramolecular exchange processes, has been described. The process leading to positional exchange of identical ligands is called ‘topomerization’, and the indistinguishable species involved are called ‘topomers’. Positional exchange between distinguishable chemical and/or magnetic environments is called ‘heterotopomerization’, e.g. exchange of apical and radial ligands in a t.b.p. phosphorane, and positional exchange between identical environments is called ‘homotopomerization’, e.g. interconversion of staggered conformers of CH3CF3by rotation about the carbon-carbon bond.67 The evidence for Berry pseudorotation and turnstile rotation has been reviewed.68 Further evidence for the turnstile rotation for spiro-pentaoxyphosphoranes has been presented, based on the lowering of the exchange barrier as the distortion of the t.b.p. of the phosphorane increase^.^^ A H. Schmidbaur, K.-H. Mitschke, and J. Weidlein, Angew. Chem. Internat. Edn., 1972, 11,144. O4 A. Rauk, L. C. Allen, and K. Mislow, J. Amer. Chem. SOC.,1972, 94, 3035. IsR. Hoffmann, J. M. Howell, and E. L. Muetterties, J. Amer. Chem. SOC.,1972, 94, 3047. O0 J. B. Florey and L. C. Cusachs, J. Amer. Chem. SOC.,1972, 94, 3040. G. Binsch, E. L. Eliel, and H. Kessler, Angew. Chem. Internat. Edn., 1971, 10, 570. P. Gillespie, P. Hoffman, K. Klusacek, D. Marquarding, S. Pfhol, F. Ramirez, E. A. Tsolis, and I. Ugi, Angew. Chem. Internat. Edn., 1971, 10, 687. OS F. Ramirez, S. Pfohl, E. A. Tsolis, J. F. Pilot, C. P. Smith, I. Ugi, D. Marquarding, P. Gillespie, and P. Hoffman, Phosphorus, 1971, 1, 1.

260 Organophosphorus Chemisiry comparison of intramolecular exchange for five- and six-membered monoand bi-cyclic oxyphosphoranes (14) and (15) has shown that exchange is restricted to radial-apical switching for the five-membered cyclic compounds whereas the compounds with six-membered rings are not so re~tricted.,~A study of the bicyclic oxyphosphorane (38), indicated that non-bonded interactions are also an important factor determining Small ring inhi bits exchange via ionization and thisproexchange cess is absent from the ligand-exchange processes for (38) and (39). As the

ring size increases ionization becomes important and loss of POCH coupling occurs in (40) at 100 "C and loss of coupling in (41) occurs at 25 O C . ? l The exchange process in the bicyclic dioxyphosphorane (42; Y = CF,), which occurs uia the high-energy t. b.p. structure (43 ;Y = CF,), is readily observed. This process involves placing the group Z in an apical position. The exchange

barriers for a series of compounds (43; Y = CF,) with a variety of substituents Z have given estimates of the relative apicophilicities of Z, i.e. the tendencies of the Z groups to occupy an apical position. For carbon substituents the order of apicophilicity decreased with electronegativity, which is the reverse of what might be expected. It appears that the apicophilicity may depend on a balance of electronegativity and ability to back-bond to phosphorus from a radial po~ition.'~Confirmation that the placing of a four-membered ring in a diradial position does not present an insurmountable barrier is obtained from the n.m.r. spectra of (44). The spectrum at - 100 "C corresponded to a mixture of (44) and (45) in a ratio of 2.3 to 1 . In (45) the strain of placing the small ring diradial is balanced by the placing of all the carbon atoms radial and the fluorine 70

71 72

D. W. White, N. 5. De'Ath, D. Z . Denney, and D. B. Denney, Phosphorus, 1971,1,91. D. B. Denney, D. Z . Denney, C. D. Hall, and K. L. Marsi, J. Arner. Chem. SOC.,1972, 94, 245. R. E. Duff, R. K. Oram, and S. Trippett, Chem. Comm., 1971, 1011; R. K. Oram and S. Trippett, J.C.S. Chem. Comm., 1972, 554.

Physical Methods

But Q

oI 0-P'

atoms

F F... I P-N y'l I ..Y N-P, I F F

F

I'F F

Variable-temperature spectra of the fluorophosphoranes

(46),74(47),76and (36)62are also reported. It is believed that the marked

changes which occur in the variable-temperature spectra of (36) may be related to slow rotation about the P-S bond.62 Restricted Rotation.-Several studies have been reported on P-N c o r n p o ~ n d s . ~Restricted ~-~~ rotation about the P-N bond in the dimethylaminophosphines (48) is observed with a variety of phosphorus substituents ; the barrier was largest for (48; Y = C1, Z = Ph).7s However, in the (methoxymethy1amino)phosphines (49) slow rotation was not detected

x,

Y

Me,CH-N

,P-Nl

Me

OMe

/ ii

\ !l

X

down to - 130 "C for the dihalogenophosphines (49;X = Y = halogen) or those with a P-F group, but only for the chloro- or bromodiaminophosphines (49; X = C1 or Br, Y = NMeOMe).77 The PIv 73

'*

75

76

77 78 79

N. J. De'Ath, D. Z . Denney, and D. B. Denney, J.C.S. Chem. Comm., 1972,272. M. Eisenhut and R. Schmutzler, Chem. Comm., 1971, 1452. R. K. Harris, J. R. Woplin, R. E. Dunmur, M. Murray, and R. Schmutzler, Ber. Bunsengesellschaftphys. Chem., 1972, 76, 44. M. P. Simonnin, C. Charrier, and R. Burgada, Org. Mugn. Resonance, 1972, 4, 113. A. Hung and J. W. Gilje, J.C.S. Chem. Comm., 1972, 662. W. B. Jennings, Chem. Comm., 1971, 867. M. J. C. Hewson, S. C. Peake, and R. Schmutzler, Chem. Comm., 1971, 1454. T. T. Bopp, M. D. Havlicek, and 5. W. Gilje, J. Amer. Chem. Soc., 1971, 93, 3051.

262

Organophosphorus Chemistry

compound (50) contains a chiral phosphorus group, which means that slow rotation about the P-N bond would give two diastereotopic isopropyl groups, and indeed four methyl doublets were observed in the spectrum run at -100 "C. The rotational barrier is believed to depend on steric and n-bonding effects.78 The low-temperature 19Fn.m.r. spectra of 2-methylpiperidyltetrafluorophosphorane (5 1) showed distinct apical and radial fluorine atoms, as expected, but in addition non-equivalent radial fluorine

Me

atoms were observed. This is attributed to a preference for the conformation shown in (51). On the other hand, the phenyl derivative (52) shows non-equivalent radial fluorine atoms, in accordance with a preference for the conformation shown in (52), i.e. the one with the methyl group oriented away from the bulky phenyl group.79 The variabletemperature 19Fn.m.r. spectra of the hydrazine derivative (53) are very interesting. The spectra contain a doublet at 160 "C, two doublets at -40 "C, and six doublets at - 145 "C. The spectra may be rationalized

(534

(534

(53b)

if (a) (53) possesses an sp2nitrogen within a planar PNNP framework, (b) there is slow interconversion of (53) and its trans-isomer (AG* = 13.0 kcal mol-l), and (c) there is restricted rotation about the P-N bond (AG* = 6.4 kcalmol-l). Thus at - 145 "C the spectrum shows the presence of three conformations of the cis-isomer (53a-c) and another three similar conformations for the trans-isomer.80 The equilibria involving the cis- and trans-conformations of the stable ylides (54a) and (54b) are dependent on the solvent and on the nature of the a-substituent R, the trans-conformer (54a) being favoured by polar solvents and R = Me.81 Ph3P

\

H

Ph,P

6

R

I

cc-cv

R R! ! o

0

I / \ / / /

c-c -~

/

/

H

(544

C. J. Devlin and B. J. Walker, Tetrahedron Letters, 1971, 4923.

263

Physical Methods

Inversion, Non-equivalence, and Configuration.-Analysis of SCF-LCAO calculations indicates that whereas the inversion of ammonia is dominated by electronic repulsions, the inversion of phosphine is controlled by nuclear repulsion. The phosphorus d-orbital functions markedly affected the properties of both the pyramidal and planar states.82 An n.m.r. study of the inversion of phosphole derivatives such as (55) has shown that even in complex spin systems a relatively accurate estimate of the inversion barrier may be obtained without recourse to a complete lineshape analysis. In this study, alkyl and aryl substituents did not Me /'p'

(55)

OMe

I

OMe

Ph

Ph

(57)

significantly influence the unusually low inversion barriers. The spectra of the phosphindole (56) and the dibenzophosphole (57) show a significant increase in the barrier height (ca. 8 and 10 kcal mol-l, respectively). The increase is attributed to the disruption of the phosphole 'aromaticity' which is responsible for the low inversion barrier in (55).83 Estimates of the influence of bond angles on inversion barriers indicate that the barrier for shallow pyramidal structures is dependent mainly on the ground-state geometry whereas the barrier for deep pyramidal structures is dependent on the bending force c ~ n s t a n t . ~A* limit to the application of free-energy relationships has been found for inversion barriers of less than 5-10 kcal m01-l.~~The lowering of the inversion barrier of the trimethoxysilylphosphine (58) compared to the trimethylsilyl derivative has been attributed to negative hyperconjugation, since the same effect was observed for a similar nitrogen compound (59).86 N.m.r. was used to follow the rate of conversion of (60) into the cis-isomer, which is presumed to occur via the Prrr form (61). The activation energy was estimated to be 23 kcal m01-l.~' Non-equivalence of the methylene protons of (62) was observed for a solution in carbon tetrachloride but not for a solution in deuterium oxide - a solvent which could break up the intramolecular hydrogenbonding shown in (62).88 Also, non-equivalence of the methyl groups was 82

84 86

88

J. M. Lehn and B. Munsch, Mol. Phys., 1972, 23, 91. W. Egan, R. Tang, G. Zon, and K. Mislow, J. Amer. Chem. SOC.,1971, 93, 6205. J. Stackhouse, R. D. Baechler, and K. Mislow, Tetrahedron Letters, 1971, 3437. J. Stackhouse, R. D. Baechler, and K. Mislow, Tetrahedron Letters, 1971, 3441. R. D. Baechler and K. Mislow, J.C.S. Chem. Comm., 1972, 185. E. Ye Nifant'ev and A. A. Borisenko, Tetrahedron Letters, 1972, 309. D. W. White, Phosphorus, 1971, 1, 33.

264 Pri

OMe

\

/

/

\

P-Si-OMe

Ph

OMe

-

Organophosphorus Chemistry Pr'

\+

-OMe

P=Si-OMe

/

Ph

\

OMe

(58)

0

OH

observed in the alkyl phosphinates (63; R = alkyl) but not in the corresponding phenyl phosphinate (63; R = Ph).s9 The diastereomeric salt of (- )-a-phenylethylamine with the (-)-thioic acid (64)has a 8p at lower field than that with the (+)-thioic acid.90 Spin-Spin Coupling.-The use of double-resonance techniques g1 is increasing rapidly. Heteronuclear PH decoupling has been used to determine the structures of p h o ~ p h a t i d e s ,and ~ ~ the Overhauser effect has assisted in conformational studies of dinucleotide~.~~ Some studies of spin systems containing phosphorus are discussed in the Specialist Periodical Report on n.m.r. (ref. 1, p. 205). Jpp and JPM. The PP coupling constants of a stereoisomeric mixture of 1,2-dimethyl-l,2-diphenyldiphosphine(65) and (66) (- 215 and - 234 Hz, respectively) were determined by double irradiation of the weak 31Ptransition. The difference is attributed to a difference in internal rotation about the P-P bond.g4 The couplings between the PIr1and PIv atoms in the corresponding mono- and di-sulphides were remarkably as W. G . Bentrude, W. D. Johnson, W. A. Khan, and E. R. Witt, J. Org. Chem., 1972, s1

sa

s3 s4

37, 631. M. Mikolajczyk and J. Omelanczuk, Tetrahedron Letters, 1972, 1539. W. von Philipsborn, Angew. Chem. Internat. Edn., 1971, 10, 472. M. Kates and A. J. Hancock, Biochem. Biophys. Acta, 1971, 248, 254. M. Kainosho and Y. Kyogoku, Biochemistry, 1972, 11, 741. H. C. E. McFarlane and W. McFarlane, Chem. Comm., 1971, 1589.

265

Physical Methods O

..

Me

Ph

.Me

(65)

Ph

(66)

Y

Y

P11

/ \

Ph

OEt

(67)

similar (-230 and -240 Hz respecti~ely).~~ In contrast, a change from 198 to 78 Hz was observed on co-ordinating nickel carbonyl with the PII1 atom in (67).95 Hydrogen-bonding had a considerable effect on lJpp of the mixed oxide sulphides (68) and (69). Coupling constants of 591 and

401 Hz in deuteriochloroform were raised to 618.5 and 513 Hz in trifluoroacetic acid. CNDO-SCF calculations indicate that hydrogenbonding to the phosphoryl oxygen of (68) (which is expected to predominate) has a small effect on coupling whereas hydrogen-bonding to the sulphur (which presumably occurs to a lesser degree) has a much larger effect. For (69) the maximum calculated effect occurred when both oxygen and sulphur were hydrogen-bonded.ss The magnitude of JpNPvaries from 0 to nearly 500Hz. A larger temperature-dependence of JPNPfor the tetrafluoro-derivatives (70) of ca. 435 Hz at + 60 "C and ca. 470 Hz at - 60 "C suggests that steric 0

FZP,

'N I

R

(70)

PF2

..

II (MeO),P,N,P(OMe), I Me (71)

MeS

0

\

4

/

\

F-P=N-P-F F

F

(72)

interactions are i m p ~ r t a n t .The ~ ~ PNP coupling tends to decrease as P I I I atoms are converted into PIv, e.g. it falls to 54 Hz for (71) and 8.3 Hz for the corresponding mixed oxide sulphide.s8 However, it is high again, J p ~ p= 107 Hz, in (72) and similar compounds with a PN multiple bond.Qg The magnitudes of J p B of borane adducts with PIr1compounds have been 95

g6 @'

O8

@O

G. Bergerhoff, 0. Hammes, J. Falke, B. Tchanyi, J. Weber, and W. Weisheit, Tetrahedron, 1971, 27, 3593. W.J. Stec, J. R. Van Wazer, and N. Goddard, J.C.S. Perkin 11, 1972, 463. E. Niecke and J. F. Nixon, Z . Nuturforsch., 1972, 27b,467. I. A. Nuretdinov, V. V. Negrebetskii, A. 2. Yankelevich, A. V. Kessenikh, L. K. Nikonorova, and E. I. Loginova, Bull. Acad. Sci. U.S.S.R.,1971, 2460; I. A. Nuretdinov, V. V. Negrebetskii, A. Z. Yankelevich, A. V. Kessinikh, E. I. Loginova, L. K. Nikonorova, and N. P. Grechkin, Dokludy Chem., 1971,196,161 ; R. Keat, Phosphorus, 1972, 1, 253. H. W. Roeski and L. F. Grimm, Chem. Comm., 1971, 998.

266

Organophosphorus Chemistry

measured lol and examined as a possible means of measuring dative bond strengths. The coupling was largest (97 Hz) for (73; X = OMe) and smallest (39 Hz) for (73; X = F).lo0 Values of lJpse have been determined for several selenides (74) and fall in the range 840-1100 Hz,lo2and values ~JPc,-J and lJpsn are reported.lo3*lo* loot

X

/

JPc. Values of lJpc and 2 J p ~of trialkylphosphines fall in the range 11-34 Hz, whilst 3 J p ~is 11-13 Hz. The coupling constant lJpc was negative for trimethylphosphine (- 13.6 Hz). This was rationalized in terms of reduced s-character of the phosphorus bonding orbitals as estimated from bond angles. This approach leads to a change in sign from positive to negative when the s-character falls below 0.15. The large magnitude of lJpc (33.9 Hz) for tri-t-butylphosphine may then be attributed to the reverse of this effect. In fact, if the coupling is positive, the calculated bond angle is identical with the experimental However, on examining the coupling constants for a wide range of phosphines, it is disconcerting to find an absence of coupling constants below 12.5 Hz, i.e. there is a rather large gap (25 Hz) in the middle of the range if the couplingconstant passes through zero. A zero l J p ~ ( ~ lis k )reported for the diphosphine (75) and also for the trans-isomer of (76), but a coupling constant of 7.9 Hz is recorded for the cis-isomer of (76) and 25 Hz for Ph2PCH,CH2PPh2

Ph2PCH=CHPPh3

(75)

(76)

6,Me d" (78a)

\*

Me

(7W

R. W. Rudolph and C. W. Schultz, J. Amer. Chem. SOC.,1971, 93, 6821. C. Jouany, G . Jugie, and J. P. Laurent, Bull. SOC.chim. France, 1972, 880. Io2 I. A. Nuretdinov and E. I. Loginova, Bull. Acad. Sci. U.S.S.R., 1971, 2252. lo3 B. E. Mann, Inorg. Nuclear Chem. Letters, 1971, 7 , 595. l o 4 P. G. Harrison, S. E. Ulrich, and J. J. Zuckerman, Znorg. Nuclear Chem. Letters, 1971, 7, 865. lo6 See ref. 17.

loo

lol

267 Physical Methods (77).loS Crowding appears to cause the larger couplings. Thus lJpc is 21.5 Hz for (78a) and 17.5 Hz for its isomer (78b).41 The effect is more dramatic for 2 J p but ~ in reverse. Thus 2 J p to ~ the crowded methyl groups (Me*) in (78a) 41 and (79) lo' is very small ( 0 - 5 Hz), and the coupling to MeB in (78b) and (79) is much larger (27-34 Hz). The corresponding one- and two-bond coupling constants to the vinyl carbon atoms in (18) and (19) also vary considerably (1-33 Hz). As more data become available it will be interesting to see whether the very low magnitude (1.4 Hz) of the cis three-bond PC coupling in (18) is characteristic or The signs of the coupling constants to aromatic sp2 carbon atoms have been determined. Values of lJPc for the tri-2- and 3-thienylphosphines are negative (- 22.7 and - 14.0 respectively) whereas the two-, three-, and four-bond couplings are all positive.40* log Thus the parallel behaviour of the signs of JPc and JFCin aliphatic phosphines and fluorides100also holds for the aromatic series. Likewise, lJpc in the phosphadiazole (80) is also negative. The large negative magnitude of this constant (- 36 Hz) indicates a low s-character for the phosphorus P-C orbita1.ll0

The steric effects of Jpc in PIv compounds are less than in P1Ircompounds but still discernible, as shown by a study of derivatives of the phosphetan (81).ll1 The magnitude of lJpc, which is generally in the region of +30 to + 60 Hz for alkyl phosphonium salts, increases as electronegative substituents are introduced on phosphorus, e.g. lJpc is 88 Hz for (82) 112

+

0 II AcO.CH,.P(CH,Br),

*

+

(82)

+

MeP(OMe)3 BF4(83)

and 132.4 Hz for (83).l13 The effect of carbon substituents has been studied using the phosphonates (22). The values of lJpc were in the range 126-139 Hz and correlated linearly with the calculated P-C s-bond order. H. Marsmann and H. G. Horn, 2. Naturforsch., 1972, 27b, 137. G. A. Gray and S. E. Cremer, J.C.S. Chem. Comm., 1972, 367. lo* H. J. Jakobsen, T. Bundgaard, and R. S. Hansen, Mol. Phys., 1972, 23, 197. log F. J. Weigert and J. D. Roberts, J. Amer. Chem. SOC.,1971, 93, 2361. 110 V. V. Negrebetskii, A. V. Kessenikh, A. F. Vasil'ev, N. P. Ignatova, N. I. ShvetsovShilovkii, and N. N. Mel'nikov, J. Struct. Chem., 1971, 12, 731. G. A. Gray and S. E. Cremer, Tetrahedron Letters, 1971, 3061. J. C. Clardy, G. K. McEwen, J. A. Mosbo, and J. G . Verkade, J. Amer. Chem. SOC.,

loo lo'

1971, 93, 6937.

lla

R. D. Bertrand, F. B. Ogilvie, and J. G. Verkade, J. Amer. Chem. SOC.,1970,92, 1908.

268

Organophosphorus Chemistry

A distinction between the cis and trans geometries of methylphosphinetransition-metal complexes has been possible by considering the triplet nature of the methyl proton signal arising from the virtual coupling in the tmns-isomers, (ref. 8a, p. 293). A similar effect is observed in the 13C n.m.r. spectra, and the effect is not limited to methy1pho~phines.l~~ lJpH. The PrrrH coupling constant tends to increase with P-C conjugation, e.g. 190 i- 10 Hz for dialkylphosphines, 210 rt 10 Hz for phenylphosphines, and ca. 240 Hz for diphenylphosphine. The introduction of trimethyl-silicon, -germanium, and -tin substituents in phenylphosphine (84) lowers l J pto ~ 201, 195, and 187 Hz, in accordance with a

PhPHM Me, (84)

i\

Me H

change in electronegativity The cyclic phosphonium salt (85) possesses l J p ~498 Hz and 2 J p 16.2 ~ ~ Hz. The couplings are opposite in sign, in accordance with positive and negative signs re~pectively.~~ The replacement of a methyl group of trimethylphosphine by SMe or an electronegative group raises 2 J p from ~ ~ 2.7 to 5-9 HZ,,~? 116 and a second such substituent raises it 24 to 8-20 Hz; the largest magnitude is shown by dibromomethylphosphine. Considerable variation of J ~ C H occurs in the vinylphosphines, e.g. 0.1 Hz for (18; Y = NMe,) and +21.4 HZ for (19; Y = NMe2).l17 This reflects the marked dependence of the coupling constant of PI1' compounds on the orientation of the lone pair of electrons, a factor which is absent for PIv compounds.ll* The geminal coupling constant for pure methylenetriphenylphosphorane (86)

JpC,H.

Y

(87; Y = CFJ

in deuteriobenzene 119 is 7.5 Hz, somewhat lower than J ~ C for H trimethylphosphonium ylides or vinylphosphonium salts (ref. 8c, p. 265, and ref. 8a, p. 297). Geminal PCH coupling constants for the oxyphosphoranes (87) were in the range 11-30 Hz.120 114 115 116

11'

118

119 120

B. E. Mann, B. L. Shaw, and R. E. Stainbank, J.C.S. Chem. Comm., 1972, 151. P. G. Harrison, S . E. Ulrich, and J. J. Zuckerman, Inorg. Chem., 1972, 11, 25. F. Seel, W.Gombler, and K. D. Velleman, Annalen, 1972, 756, 181. R. M. Lequan and M. P. Simonnin, Tetrahedron Letters, 1972, 145.

F. A. Carey and A. S . Court, J. Org. Chem., 1972, 37, 939. H. Schmidbaur, H. Stahler, and W. Vornberger, Chem. Ber., 1972, 105, 1084. Mazhar-ul-Haque, C. N.Caughlan, F. Ramirez, J. F. Pilot, and C. P. Smith, J. Amer. Chem. SOC.,1971, 93, 5229.

269

Physical Methods

The vicinal PCCH coupling constants involving the carbon-carbon bond of the cyclopropyl ring in the compounds (88) fall into two ranges, namely 1-4 and 15-17 Hz. The larger couplings are assigned to the cis-compounds, owing to the dihedral angle of O", and the smaller couplings are assigned to the trans-compounds (120" dihedral angle).121 Values of JPCCHare small when a carbonyl group is part of the link (ref. 8b, p. 253) and almost zero when an imino-group interposes, e.g. as in the pyrazolinyl derivatives (89; R = Y = Ph)122 and (89; R = Et, Y = O-).123 The

(88)

(89)

smaller cis PC:CH coupling constants compared to the trans-coupling is well recognized; it is found that an a-halogen substituent reduces the The well-recognized large vicinal coupling cis-coupling further to 7 constants ( 2 8 4 0 Hz) for the PIv compounds apply equally to the dihydroand tetrahydro-derivatives (90) and (91).125 In a study of the methyl derivatives of trithienylphosphines (92) it was found that an ortho-methyl Ph, ,H

Ph

group reduces 3JpH by half, and that 4JpH is more than doubled. The effect was not observed in the sulphide derivatives and therefore appears to be connected with the orientation of the lone pair of electrons on phosphorus.126 A number of derivatives of the oxyphosphoranes derived from (93) have now been prepared. Most of the compounds possessed a value of JPCCH in the range 34-38 Hz or 8-11 Hz. The protons with the larger couplings are attributed to HA, which is anti to the phosphorus atom.32 lZ1

lZs 124

lZ6

H. Gunther, B. D. Tunggal, M. Regitz, H. Scherer, and T. Keller, Angew. Chern. Znternut. Edn., 1971, 10, 563; H. J. Callot and C. Benezra, Cunad. J. Chem., 1972, 50, 1078. E. E. Schweizer and C. S. Kim, J. Org. Chem., 1971, 36, 4033. A. N. Pudovik, R. D. Gareev, A. V. Aganov, 0. E. Raevskaya, and L. A. Stabrovskaya, J . Gen. Chem. (U.S.S.R.), 1971, 41, 1013. V. V. Moskva, T. V. Zykova, V. M. Ismailov, and A. I. Razumov, J . Gen. Chem. (U.S.S.R.), 1971, 41, 89. A. Hettche and K. Dimroth, Tetrahedron Letters, 1972, 829; G. Markl, A. Merz, and H. Rausch, ibid., 1971, 2989; A. Hettche and K. Dimroth, ibid., 1972, 1045. H. J. Jakobsen and M. Begtrup, J . Mol. Spectroscopy, 1971, 40, 276.

0rganophospho rus Chemistry

270

Ph

Cross-conjugation often greatly diminishes spin-spin coupling,122* 123 but this is not without exception because the oxyphosphorane (94) has J ~ C C H= ~ 37 Hz.12’ A long-range coupling has been reported for the phosphine oxide (95); 5JpH is 1.2 Hz, which is not as large as the coupling through an olefinic ~ 5.4 HZ for (96).128 bond, e.g. 6 J p = Me,

I1

,PPh?

,Me C II

H,c\

0 II ,P(OW, CH2

and JPXC,H. The dependence of J p o C H on stereochemistry continues to be used extensively for conformational studies, especially with the cyclic phosphonates (97),12’9 130 and has also been extended to the study of amide derivatives (98).131 Some values of J p s c ~are similar to

JpXH

Me

lZ7 lZ8 lZ9

D. D. Swank, C. N. Caughlan, F. Ramirez, and J. F. Pilot, J . Amer. Chem. SOC.,1971, 93, 5236. T. E. Snider and K. D. Berlin, Phosphorus, 1971, 1, 59. J. P. Majoral, R. Pujol, 5. Navech, and F. Mathis, Tetrahedron Letters, 1971, 3755. W. G . Bentrude and K. C. Yee, J.C.S. Chem. Comm., 1972, 169; J. P. Majoral, R. Pujol, and J. Navech, Compt. rend., 1971, 272, C, 1913. R. Kraemer and J. Navech, Bull. SOC.chim. France, 1971, 3580.

Physical Methods

27 1

those of JPOC~.132 A study of the effect of 0-protonation and -alkylation increases slightly of the oxides (99; Y = OMe or NMe,) showed that JPOCH remains essentially ~ 0 n s t a n t . lThe ~ ~ PNCH coupling constants whilst JPNCH of a wide range of oxides (100) 13* were scattered within the range 8-17 Hz, whereas J ~ N C Hfor the PIr1cyclic compounds (101) fall into two groups, 2.2-3.5 and 5.9-10.9 Hz, depending on the s t e r e ~ c h e m i s t r y .A ~ ~value ~ of the PCNH coupling of 12 Hz is reported for and PNH couplings of 17.7 and 21 Hz for the Pv compounds (103) 13' and (104).138

Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies.-A study of the relaxation times of phosphoryl compounds at two magnetic fields, and of the dependence of spin rotation and dipolar interactions upon viscosity and temperature, led to the approximate separation of dipole-dipole, anisotropy, and spin-rotation interactions, and indicated that second-order paramagnetic shielding was dominant.139 The 31Prelaxation times TI and Tz were determined for several lipid-water phases. Comparisons of changes of T2which occur at the transition temperature for dipalmitoyllecithin indicated that the relaxation times reflect the mobility of the lipid head-group.140 PH Decoupling of trialkyl phosphites and phosphates by paramagnetic reagents only occurs when there is direct co-ordination. In most cases 8p is shifted downfield, but 8~ showed no definite trend. The most effective reagent was cobalt chloride in acetonitrile s01ution.l~~ The H-1 proton of dinucleotide mono- and di-phosphates was identified by the broadening of its resonance that occurred upon the addition of Mn2+ ions.142 A study of the effects of paramagnetic ions on adenosine 5'-monophosphate has also been ~ e p 0 r t e d . l ~ ~ A comparison of the calculated and observed n.q.r. resonances has been used to study the stereochemistry and bonding of chloro-compounds such as (105), (106), and (107). The 35Cl n.q.r. resonances of the thiophosphoryl chlorides were higher than those of the phosphoryl chlorides. This was attributed to reduced p,-d, back-bonding from the sulphur lsa lSs

13' la6 lS6

lS7 lS8 lS9

140

141 143

A. Zwierzak and R. Gramze, Z . Naturforsch., 1971, 26b, 386; B. Krawiecka and J. Michalski, Bull. Acad.polon. Sci., Sbr. Sci. chim., 1971, 19, 377. K. E. DeBruin, A. G. Padilla, and D. M. Johnson, Tetrahedron Letters, 1971, 4279. I. Irvine and R. Keat, J.C.S. Dalton, 1972, 17. J. P. Albrand, A. Cogne, D. Gagnaire, and J. B. Robert, Tetrahedron, 1972, 28, 819. T. Nishiwaki and T. Saito, J. Chem. SOC.(0,1971, 3021. A. H. Cowley and J. R. Schweiger, J.C.S. Chem. Comm., 1972, 560. A. Munoz, M. Koenig, B. Garrigues, and R. Wolf, Compt. rend., 1972, 274, C, 1413. S. W. Dale and M. E. Hobbs, J. Phys. Chem., 1971, 75, 3537. R. W. Barker, J. D. Bell, G. K. Radda, and R. E. Richards, Biochirn. Biophys. Acta, 1972, 260, 161. R. Engel and L. Gelbaum, J.C.S. Perkin I , 1972, 1233. K. N. Fang, N. S. Kondo, P. S. Miller, and P. 0. P. Ts'O, J. Amer. Chem. SUC.,1971, 93, 6647; A. W. Missen, D. F. S. Natusch, and L. J. Porter, Austral. J . Chem., 1972, 25, 129.

272

Organophosphorus Chemistry

atom.143 A similar conclusion was made after a study of the aminophosphine chalcogenides (108; X = 0, S , or Se). It was also found that the occupation number of the nitrogen atom is independent of the phosphorus co-ordination number.144 The 35Cl n.q.r. spectra of alkyldichlorophosphines and their sulphides (109) have been ~ e p 0 r t e d . l N.q.r. ~~ has

also been used to investigate the existence of five-co-ordinate chlorophosphoranes and the orientation of the chlorine atoms in the t.b.p. The phenyl derivatives (1 10) were found to be quasiphosphonium 2 Electron Spin Resonance Spectroscopy y-Irradiation of phosphonium salts and phosphines in sulphuric acid has been studied. The e.s.r. spectra from phosphines corresponded to the radical ( l l l ) , and a comparison with PH3 indicated that the alkyl groups increase the pyramidal character (probably owing to hyperc~njugation).~~~

Although there is chemical evidence for non-equivalence of alkoxy-groups in radicals of the type (112),l4' the e.s.r. resonance of (113) showed no resolvable fine-structure.14* The spectrum of (1 14) indicates that the radical is non-planar, with a phosphorus 3 p character of 0.6 (cf. 0.41 2p character for the planar radical PhzfiO).149The unpaired electron is confined mainly to the sulphur atoms in the thiophosphate radical (115), the spin density in the phosphorus 3s orbital (ca. 0.7%) being similar to that 143 144

146 148 147 148

149

R. M. Hart and M. A. Whitehead, J. Chern. SOC.(A), 1971, 1738. D. Y. Osokin, I. A. Safin, and I. A. Nuretdinov, Doklady Chem., 1971, 201, 981. J. K. B. Bishop, W. R. Cullen, and M. C. L. Gerry, Canad. J . Chem., 1971,49, 3910. A. Begum, A. R. Lyons, and M. C. R. Symons, J. Chem. SOC.(A), 1971, 2290, 2388. W. G. Bentrude and T. B. Min, J. Amer. Chem. SOC.,1972, 94, 1025. A. G. Davies, D. D. Griller, and B. P. Roberts, Angew. Chem. Internat. Edn., 1971, 10, 738. M. Geoffroy and E. A. C. Lucken, Mol. Phys., 1971, 22, 257.

273

Physical Methods

observed for phosphate r a d i ~ a 1 s . lThe ~ ~ reaction of phospholes (1 16) with alkali metals at low temperature gave e.s.r. spectra corresponding to a mono-anion radical. The coupling to the phosphorus nucleus was very large and the spectra support the postulate that there is considerable aromaticity in the phosphole ring.151 The cation-free anion radicals produced by electrochemical reduction of triphenylphosphine, its oxide, and their deuterium analogues had similar e.s.r. spectra, which were independent of solvent. The spectra of the [ 2 H l o ] - ~ ~ m p ~i.e. ~ n(1d17) ~,

and its oxide, did not correspond to superimposed spectra of the [2H15]and [2H,]-compounds in a 2 : 1 ratio, and therefore the electron is delocalized over all three aryl rings in the phosphine and its The e.s.r. spectra of radicals of the type (118) and its PIv derivatives indicated a large, almost isotropic, interaction with the phosphorus atom, which indicates that there is a significant interaction with the valence s-orbital of phosphorus. The interaction is believed to be hyperconjugative 0

and at a maximum for the conformation shown in (118),153 and at a minimum when the p-orbital is at right angles to the C-P bond. The corresponding phosphonite radicals have been examined by e.s.r. spectros c ~ p y . ~In~the * p-dichloro-compounds (1 19) the magnitude of the coupling to H* and the phosphorus nucleus varied in opposite directions, which supports the angular dependence for the i n t e r a ~ t i 0 n . l ~Steric ~ effects 150

161 152

15s

M. Sato, M. Yanagita, Y. Fujita, and T. Kwan, Bull. Chem. SOC.Japan, 1971,44,1423. D. Kilcast and C. Thomson, Tetrahedron, 1971, 27, 5705. A. V. Il'yasov, Y. A. Levin, I. D. Morozova, A. A. Vafina, I. P. Gozman, and E. I. Zoroatskaya, Doklady Chem., 1971, 201, 898. A. R. Lyons and M. C. R. Symons, Chem. Comm., 1971, 1068; J.C.S. Faraday ZI, 1972, 68, 622.

154 156

A. G. Davies, D. Griller, and B. P. Roberts, J. Amer. Chem. SOC.,1972, 94, 1782. W. Damerau, G. Lassmann, and K. Lohs, J. Magn. Resonance, 1971,5,408; 2. Chem., 1971, 11, 182.

274 Organophosphorus Chemistry altering spin transmission, uia hyperconjugation, have also been proposed for the nitroaryl radicals (120; X = 0 or S).156 Spectra are also reported for phosphazenes 15' and for imino-oxyl 15* and peroxyl radi~a1s.l~~ E.s.r. has been used to study paramagnetic proteins which are important in the respiratory chain.160 0

R\

R' 1 20)

3 Vibrational Spectroscopy Band Assignment and Structural Elucidation.-The change in frequency of v(PH) from 2410 to 1753 cm-l upon deuteriation confirmed the presence of a PH bond in (121).lS1 In contrast to v(0H) of acidic and alcoholic OH groups, v(PH) of the phosphonium salt (121) is at higher wavenumber than v(PH) for primary and secondary phosphines (ca. 2300 cm-l), and it is still

(121)

( 122)

higher (ca. 2460 cm-l) for the Pv oxyphosphoranes (122).la2 The fundamental P-C frequencies have been identified in the spectra of difluoroand dichloro-t-butylphosphines and their ~ha1cogenides.l~~ Bands in the OH stretching region, 3200-3300 cm-l, in the spectra of the alcohol (123 ;R = Me or CH,NO,) are assigned to polymeric associates, whereas the bands which appear at 3550-3580 cm-l in dilute chloroform solutions are attributed to monomers with a free hydroxy-group and/or an intramolecular hydrogen-bonded structure. In dilute carbon tetrachloride lS6 lS7

158 159

160 181

le2 163

W. M. Gulick, J . Amer. Chem. SOC.,1972, 94, 29. H. R. Allcock and W. J. Birdsall, Znorg. Chem., 1971, 10, 2495. A. Nakajima, H. Ohya-Nishiguchi, and Y. Deguchi, Bull. Chem. Soc. Japan, 1971,44,

2 120. G. B. Watts and K. U. Ingold, J. Amer. Chem. SOC.,1972, 94, 2528. E. C. Slater, I. Y . Lee, B. F. Van Gelder, S. P. J. Albracht, and J. A. Berden, Biochim. Biophys. Acta, 1972, 256, 14; S. P. J. Albracht and E. C. Slater, ibid., 1971, 245, 508.

R. Churchman, D. G . Holah, A. N . Hughes, and B. C. Hui, J . Heterocyclic Chem., 1971, 8, 877.

A. Schmidpeter and J. Luber, Angew. Chem. Znternat. Edn., 1972, 11, 306. R. R. Holmes and M. Fild, Spectrochim. Acta, 1971, 27A, 1525, 1537.

Physical Methods

275

a band also appears at 3400-3420cm-l,

which may be due to dimeric associates, whereas in THF and acetonitrile bands in the 3450-3480 cm-l region may be due to solute-solvent Similar studies have been reported on the carboxylic acid derivatives (123; R = C02H).166 The CH group in (124) is acidic and gives bands at 2940 and 2875 cm-l. 0

The low frequency is attributed to hydrogen-bonding between the CH group and the phosphoryl oxygen. These bands were weaker in the spectrum of (124) in dichloromethane, and shifted to 3000 cm-l by adding chloroform.les A dilute solution of trimethylphosphine oxide in methanol gives a strong band at 1197 cm-l; bands appear at 1180, then at 1153 and 1120 cm-l as the solution is concentrated.ls7 Donor properties of alkoxy and dimethylamino PI1’ compounds towards hydroxylic solvents have been compared.ls8 A high-wavenumber band at 3615 cm-l in the spectrum of (125) was shown to be due to v(0H) when deuteriation caused P h,P =N Ph (125)

( 126)

a shift to 2665 cm-l.lss The effects of N-protonation, -alkylation, and hydrogen-bonding on the spectra of the phosphinimine (126) have been reported. In all cases the broad and intense band at 1350 cm-l, which these workers attribute to v(PN), is shifted dramatically to low w a v e n ~ m b e r . ~ ~ ~ Some unusual frequencies have been reported for v(C=C) in the spectra of the heterocycles (127) and (128). In (127) it appears 171 at 1565 cm-1 whereas in (128) it occurs as an intense absorption at 1730 k 5 cm-1.172 E. I. Matrosov and M. I. Kabachnik, Spectrochim. Acta, 1972, 28A, 313; E. I. Matrosov, G. M. Baranov, V. V. Perekalin, M. I. Kabachnik, and T. A. Mastryukova, Bull. Acad. Sci. U.S.S.R., 1971, 2439. lt16 A. N. Pudovik, I. V. Gur’yanova, M. G. Zimin, 0. E. Raevskaya, M. A. Shakirova, A. Kh. Mift’akhova, and V. F. Toropova, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1232. 16E E. I. Matrosov, T. Ya. Medved, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1971,

16*

1008. E. V. Ryl’tsev, I. E. Boldeskul, A. M. Pinchuk, L. N. Markovskii, and U. P. Egorov, Zhur. priklad. Spectroskopii, 1971, 15, 889. lE8 L. M. Epshtein, Z. S. Novikova, L. D. Ashkinadze, L. M. Rubasheva, and L. A. Kazitsyna, Bull. Acad. Sci. U.S.S.R., 1971, 884. lB0A. A. Pinkerton and R. G. Cavell, J. Amer. Chem. SOC.,1972, 94, 1870. 170 E. I. Matrosov, V. A. Gilyarov, V. Yu. Kovtun, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1971, 1076. 171 B. A. Arbuzov, A. P. Rakov, and A. 0. Vizel, Bull. Acad. Sci. U.S.S.R., 1971, 1885. 17a W. G. Bentrude, W. D. Johnson, and W. A. Khan, J. Amer. Chem. SOC.,1972, 94, 3058.

16?

276

Organophosphorus Chemistry

( 1 27)

Stereochemical Aspects.-The methyl torsional frequencies have been obtained for a series of fluoro- and chloro-methylphosphines and their chalcogenidesfrom the spectra in the solid and gas The spectrum of (129) is the same in all phases, and it is concluded that the molecules take up a gauche conformation, with the PNCz section ~ 1 a n a r . lThe ~~ far-i.r. and Raman spectra of trimethylphosphine indicate a CPC bond Me, N -P C I (1 29)

angle of 99.1" and P-C bond length of 1.841 A.175 The electronic effect of stannic chloride on the rotational isomers of the phosphinate (130) has been r e ~ 0 r t e d . l ~ A~gauche conformation (131) has been estimated from the i.r. spectra of some dia1kylpho~phinates.l~~ Thermodynamic parameters have been estimated for the conformational equilibria of the R

P S

cyclic phosphonates (97) from i.r. and n.m.r. data.129 The position of the conformational equilibrium for the cyclic thiophosphinates (1 32) was estimated from the absolute integral intensities of the i.r. bands associated with the different conformers. The more polar conformer was identified by its predominance in the more polar media.178Variable-temperature i.r. spectra (+ 30 to - 130 "C) of the thiophosphinates (133), as expected, indicate a very small energy difference between the rotational 17s 17*

176 176 177 178

17s

J. R. Durig and J. M. Casper, J. Phys. Chem., 1971, 75, 1956. J. R. Durig and J. M. Casper, J. Phys. Chem., 1971, 75, 3837. J. R. Durig, S. M. Craven, and J. Bragin, J. Chem. Phys., 1970, 53, 38.

E. G. Yarkova, A. A. Musina, V. P. Plekhov, A. A. Muratova, and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.), 1971, 41, 2608. 0. A. Raevskii, F. G. Khalitov, and M. A. Pudovik, Bull. Acad. Sci. U.S.S.R., 1971, 2468. E. A. Ishmaeva, 0. A. Raevskii, R. A. Cherkasov, F. G. Khalitov, V. V. Ovchinnikov, and A. N. Pudovik, Doklady Chem., 1971, 197, 302. R. R. Shagidullin and I. P. Lipatova, Bull. Acad. Sci. U.S.S.R., 1971, 940.

277

Physical Methods Mc~C--P, I F F ( 1 33)

The gas- and liquid-phase vibrational spectra and dipole moment of t-butyltetrafluorophosphorane are in accordance with the t.b.p. structure (1 34), with only slight distortion towards a square-pyramidal geometry.lgO Studies of Bonding.-Further work is reported on the force constants of the PC1, PO, and PS bonds.lsl Calculations on some compounds containing the phosphoryl bond indicate that the polarity of the PO bond is reduced by inductive donation by the remaining substituents.ls2 A number of reports of calculations on the bonding in various phosphorus halides have also been pub1i~hed.l~~" The intensities of the NH fundamental band in spirophosphoranes such as (1 35) indicate sp2 character for the nitrogen atoms owing to P-N conjugation.1s3b H

The band positions and intensities of v,,(N02) and v,(NO,) in the i.r. spectra of diphenyl p-nitrophenylphosphine (136; Y = PPh2) were compared with those of other p-substituted nitrobenzenes (136) with the aim of comparing the mesomeric effects of the substituents. The comparison was found to be less useful than anticipated.18* Correlations of ,(PO) and

v ( C 0 ) with Hammett o-constants are reported for the silyl phosphonates (137).lB5 R. R. Holmes and M. Fild, Znorg. Chem., 1971, 10, 1109. N. Fritzowsky, A. Lentz, and J. Goubeau, 2. anorg. Chem., 1971,386, 67, 203. R. M. Archibald and P. G. Perkins, Rev. Roumaine Biochim., 1971, 16, 1137. 18s (a) A. Serafini, J. F. Labarre, A. Veillard, and G. Vinot, Chem. Comm., 1971, 996; I. H. Hillier and V. R. Saunders, J.C.S. Dalton, 1972, 21; M. F. Guest, I. H. Hillier, and V. R. Saunders, J.C.S. Furaduy 11, 1972,68, 114. (b) R. Mathis and R. Burgada, Compt. rend., 1972, 274, C, 1156. lB4 G. P. Schiemenz, Phosphorus, 1971, 1, 133. lB5 V. M. D'yakov, G. S. Gusakova, E. I. Pokrovskii, and T. L. D'yakova, J . Gen. Chem. (U.S.S.R.), 1971, 41, 1040. lB0

lS1

lB2

10

278

Organophosphorus Chemistry 4 Microwave Spectroscopy

The radiofrequency spectrum of phosphine has been measured in a molecular beam electric resonance spectrometer. The suspected inversion doubling was not observed; its dipole moment (p) was 0.574 D.lg6 The calculated rotational barrier between the staggered and eclipsed conformers of methylphosphine is 1.83 and 1.71 kcalmol-l, in agreement with the experimental value of 1.96 from microwave measurements. An orbitalby-orbital analysis of the changes which occur upon rotation suggests a hydrogen-bond contribution when the phosphorus lone pair of electrons and a CH bond are appropriately orientated.lE7 The existence of a 1-2" tilt of a methyl group towards the phosphorus lone pair of electrons in methylphosphines (1 38) was a conclusion drawn from a microwave study

of the deuteriated and non-deuteriated phosphines. The CPC bond angle in trimethylphosphine was estimated to be 98.9O.lSs Co-ordination of methylphosphine and trimethylphosphine with borane decreases the P- C bond lengths, especially for methylphosphine. In fact, whereas r(P-C) of trimethylphosphine is normally the shorter bond of the two phosphines, co-ordination reverses this In the rotation of the P-P bond of diphosphine, calculations indicate that the point of minimum energy occurs between the gauche and semi-eclipsed conformers, as shown in (139).lgo Perhaps this is also the result of a balance between vicinal H,H repulsion and vicinal H,lone-electron-pair attraction. The spectra of H

phosphinodifluorophosphine indicate that the staggered conformation (140) is preferred, and it appears that hydrogen-bonding to fluorine is not sufficient to make the gauche conformer the most ~ t a b 1 e . l A ~ ~similar result was obtained for tetrafluorodiph~sphine.~~~ 186

lS7 188

1813

l90 lgl

P. B. Davies, R. M. Neumann, S. C. Wofsy, and W. Klemperer, J . Chem. Phys., 1971, 55, 3564. I. Absar and J. R. Van Wazer, J. Chem. Phys., 1972, 56, 1284; Chem. Comm., 1971, 611. P. S. Bryan and R. L. Kuczkowski, J. Chem. Phys., 1971, 55, 3049. P. S. Bryan and R. L. Kuczkowski, Inorg. Chem., 1972, 11, 553.

I. Absar, J. B. Robert, and J. R. Van Wazer, J.C.S. Faraday IZ, 1972, 68, 799. R. L. Kuczkowski, H. W. Schiller, and R. W. Rudolph, Znorg. Chem., 1971, 10,2505. E. L. Wagner, Tlteor. Chim. Acta, 1971, 23, 127.

279

Physical Methods

The microwave spectrum of aminodifluorophosphine (141) indicates a planar PNHzgroup with a HNH bond angle of 117.2' and total p 2.58 D.193 The spectra of four phosphorus trihalides are also reported.lg4 Phosphabenzene (142) has been studied; the spectrum is consistent with a CPC bond angle of 101-104', and a planar ring with the phosphorus atom involved in conjugation.^^^ An interesting theoretical study of the

hypothetical methylenephosphorane (143) indicates that there is an essentially zero barrier to C-P bond rotation with or without the inclusion of phosphorus d-0rbita1s.l~~ 5 Electronic Spectroscopy The increase in Am= and E which occurs in the U.V. spectra of tertiary phosphines upon the introduction of aryl groups is largest for mesityl groups (144; Ar = mesityl), less for o-toly' 'oups, and least for phenyl

Et ,PAr

-

3-

(144)

groups. pK, Measurements and estimates of bond angles from 8p indicate that the difference in the effects of the aryl groups is not due to an increase in the energy or p-character of the phosphorus lone pair of A charge-transfer complex between triphenylphosphine and TCNE gives intense absorptions at 502 and 374 nm.lSs A regular change occurs in the U.V. spectra of phosphonium salts (145) as alkyl groups are replaced by aryl groups, except for the dialkyldiaryl salts. This aspect has been studied using pyrrole as a readily identified aryl ~ u b s t i t u e n t .The ~ ~ ~main absorption band of aniline and dimethylaniline is strongly shifted to longer wavelengths by para PIv substituents in a manner typical of groups exerting a - M effect.200The U.V. spectra A. H. Brittain, J. E. Smith, P. L. Lee, K. Cohn, and R. H. Schwendeman, J. Amer. Chem. SOC.,1971,93, 6772. 194 A. H. Brittain, J. E. Smith, and R. H. Schwendeman, Inorg. Chem., 1972, 11, 39; K. Kuchitsu, T. Shibata, A. Yokozeki, and C. Matsumura, Inorg. Chem., 1971, 10, 2584. R. L. Kuczkowski and A. J. Ashe, J. Mol. Spectroscopy, 1972, 42, 457. lS6 I. Absar and J. R. Van Wazer, J . Amer. Chem. SOC.,1972, 94, 2382. lS7 B. I. Stepanov, A. I. Bokanov, and V. I. Svergun, J . Gen. Chem. (U.S.S.R.), 1971, 41, 526. lS8 J. R. Preer, F. D. Tsay, and H. B. Gray, J. Amer. Chem. SOC.,1972,94, 1875. lg9 G. P. Schiemenz, Tetrahedron Letters, 1971, 4689. 2 o o G. P. Schiemenz and K. Rohlk, Chem. Ber., 1971, 104, 1722. 193

0rganoph osphor us Chemistry

280

Y

(147)

( 1 45)

of p-methoxyphenyl PIv compounds (146) are not altered by changes in the p-substituents.201 Aziridine PIv compounds (147) exhibit an intense band in the region 220-247 nm and a less well-defined band near 280 f 20 nm. The bathochromic shift produced by halogens increased with the electronegativity of the halogen.202 The far-u.v. region has been used to study phosphate interactions in aqueous s o l ~ t i o n s . Phosphorus ~~~ is now regularly estimated by (a) absorption spectroscopy using the band at 436nm produced by vanadomolybdophosphate,204(b) by fiame-emission spectroscopy using the emission band at 528 nm produced by HP0,205and (c) by fluorimetry using the intense green-blue fluorescence produced by a transient indoleperoxyphosphoric acid.206 A number of photoelectron spectroscopy studies of organophosphorus compounds have been reported. ESCA spectroscopy may be used to detect changes in gross structure but does not appear to be suitable for studying fine stereochemical aspects such as differentiating between the cis- and trans-isomers of (148).207 Similar limitations were observed for the innerMe

(148)

T (1 49)

orbital photoelectron spectra of thiono-thiolo-compounds such as (149; X, Y = 0 or S).208 Also, there was only a small spread of 2p binding energies in a series of phosphonium As expected, there is a larger difference between phosphines, phosphine oxides, phosphonium salts, and phosphonic acids, but there was a poor correlation with the charge on phosphorus (as estimated by EHMO calculations).20s

208

G. P. Schiemenz, Annalen, 1971, 752, 30. L. D. Protsenko and N. Y. Skul’skaya, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1949. M. Trachtman and M. Halmann, Carbohydrate Res., 1971, 19, 245; H. Descroix, S. Puiseux-Dao, and M. Suard, Compt. rend., 1971, 272, D, 2472. J. Tusl, Analyst, 1972, 97, 111; G. Norwitz, M. Galan, and M. E. Everett, Analyt. Chim. Acta, 1971, 56, 385. W. N. Elliott, C. Heathcote, and R. A. Mostyn, Talanta, 1972, 19, 359; A. Syty, Analyt. Letters, 1971, 4, 531. W. Rusiecki, J. Brzezinski, and M. Szutowski, Acta Polon. Pharm., 1971, 28, 385. W. J. Stec, W. E. Morgan, J. R. Van Wazer, and W. G. Proctor, J. Inorg. Nuclear Chem., 1972, 34, 1100. W. J. Stec, W. E. Moddeman, R. G. Albridge, and J. R. Van Wazer, J. Phys. Chem.,

zos

M. Pelavin, D. N. Hendrickson, J. M. Hollander, and W. L. Jolly, J. Phys. Chem.,

201 202

aos 204 205

206

207

1971,75, 3975.

1970, 74, 1116.

28 1

Physical Methods

Photoelectron spectra, in combination with CND0/2 calculations, have been used to assign molecular orbitals and estimate their energies. This technique has been used to compare the electronic structure of the phosphorin (150) with that of the corresponding pyridine.210 Photoelectron But

( 1 50)

spectra have also been reported for phosphine and various phosphorus halides.211 The K spectra of triphenyl phosphite and triphenyl phosphate have been determined by X-ray emission spectroscopy.212A new theory for estimating phosphorus resonance transition probabilities has been 6 Rotation and Refraction Resolution of two heterocyclic compounds is reported. Partial resolution of the phosphonium salt (151) was achieved using silver D(-)- and L(+)dibenz~yltartrates,~~~ and the phosphine oxide (152) was resolved using ( + )-9-camphorsulphonic

(151)

( 152)

The magnetic rotations of the pyrophosphates (153; Y = alkyl or OR, X = 0) show that the linking oxygen atom interrupts the delocalization of r-electrons.216 A comparison of observed and calculated magnetic rotations of the monothiopyrophosphates shows that they have the thionostructure (153; X = S).217 The Faraday effect and diamagnetic susceptibilities of a number of Prrr-Ncompounds reflect a large variation alo

211

212 213 214

215

216 217

H. Oehling, W. Schafer, and A. Schweig, Angew. Chem. Znternat. Edn., 1971, 10, 656. M. Barber, J. A. Connor, M. F. Guest, I. H. Hillier, and V. R. Saunders, Chem. Comm., 1971, 943; P. J. Bassett and D. R. Lloyd, J.C.S. Dalton, 1972, 248; J, P. Maier and D. W. Turner, J.C.S. Furaday IZ, 1972, 68, 71 1. Y. Takahashi, Bull. Chem. Soc. Japan, 1972, 45, 4. D. R. Beck and 0. Sinanoglu, Phys. Rev. Letters, 1972, 28, 945. C. H. Chen and K. D. Berlin, J . Org. Chem., 1971, 36, 2791. G. Ostrogovich and F. Kereh, Angew. Chem. Internut. Edn., 1971, 10, 498. R. Turpin, D. Troy-Lamire, and D. Voigt, Bull. SOC.chim. France, 1971, 3878. D. Troy-Lamire, R. Turpin, and D. Voigt, Bull. SOC.chim. France, 1972, 889.

282

Organophosphorus Chemistry

o

x

of m character upon changing the electronegativities of the phosphorus substituents.21S Optical rotatory dispersion of normal and 2’4-rnethylated diribonucleoside monophosphate at pH 1, 7, and 11.2 has been used to study the conformation of the ribose part of the m o l e c ~ l e . ~ ~ ~ Circular dichroism of pyrophosphate derivatives of some purine nucleosides indicates a symmetrically stacked syn conformation except when there is restricted rotation of the base.220 Circular dichroism has also been used to study the inhibitor action of guanosine 2’(3’)-monophosphate on a ribonuclease.221 7 Diffraction The number of diffraction studies of phosphorus compounds continues to increase. A timely review of the geometric parameters of acyclic organophosphorus compounds has been published.222 The X-ray diffraction of 1,2,5-triphenylphosphole(1 54) indicates that the phosphole has little if any r-electron delocalization. The P-phenyl

group subtends an angle of 116” to the heterocyclic ring, the C-C bonds of which have typical butadiene distances, and the PC bonds correspond to single The phosphorin ring of (155) has a chair conformation with a CPC bond angle of 100” in the ring.224 The alkaline hydrolysis of 1,2,2,3,4,4-hexarnethyl-l-phenylphosphetaniumiodide gives a spiroderivative of a phosphole oxide. The structure of the corresponding spiro1,l-dimethylphospholaniumsalthas beenexaminedand thering proton found 218

21s 230

221 222 223

224

M. C. Labarre, D. Voigt, S. Senges, M. Zentil, and R. Wolf, J . Chim. phys., 1971, 68, 1216. H. Singh and B. Hillier, Biopolymers, 1971, 10, 2445. M. Ikehara, S. Uesugi, and K. Yoshida, Biochemistry, 1972, 11, 836. N. Yoshida, K. Kuriyama, T. Iwata, and H. Otsuka, Biochem. Biophys. Res. Comm., 1971, 43, 954. L. S. Khaikin and L. V. Vilkov, Russ. Chem. Rev., 1971, 40,1014. W. P. Ozbirn, R. A. Jacobson, and J. C. Clardy, Chem. Comm., 1971, 1062. A. T. McPhail, J. J. Breen, J. C. H. Steele, and L. D. Quin, Phosphorus, 1972, 1, 255.

Physical Methods

283

to be in the 2-position, as shown in (156).22bA comparison of the crystal structures of the 2-troponyl carbonyl-stabilized ylide (157) with that of the corresponding+nitrile-stabilized ylide (158) proved to be very rewarding. Whereas the P a - 0 - bond distance is 236pm in (158), it is much shorter EtO

N

Ill C

\

c=o

( 1 57)

(158)

(214pm) in the ester (157), approaching the bond length of an apical PO bond of oxyphosphoranes (176-179 pni). The distance between the phosphorus atom and the oxygen of the ester carbonyl (305pm) is also less than the sum of the van de Waals radii ( 3 3 O ~ m ) . ~The l bisphosphonium ylide (159) has the NCN group twisted 7.7" out of the PCP plane in the Two enantiomorphs were identified in crystals of the carbodiphosphorane (160). The PCP bond angle of 144" and 130" in Ph,P,

,c--c,

PW+

( I601

,NPh NPh

(161)

each enantiomorph is much greater than the 170" observed for the N=C=N group. The large angle allows two of the phenyl groups, one on each phosphorus atom, to have an almost eclipsed conformation, as shown in (160).227Reaction of this compound with Mn(CO),Br gives the complex (161), in which the triple bond (120 pm) is little changed from X-Ray diffraction studies are also reported for (162) 229 and (1 63).230 226 227 228 229

230

J. N. Brown, L. M. Trefonas, and R. L. R. Towns, J. Heterocyclic Chem., 1972,9,463. F. K. Ross, W. C. Hamilton, and F. Ramirez, Acta Cryst., 1971, B27, 2331. A. T. Vincent and P. 5. Wheatley, J.C.S. Dalton, 1972, 617. S. Z . Goldberg, E. N. Duesler, and K. N. Raymond, Chem. Comm., 1971, 826. A. F. Cameron, N. J. Hair, and D. G . Morris, Chem. Comm., 1971, 918. J. C. Williams, J. A. Kuczkowski, N. A. Portnoy, K. S . Yong, 5. D. Wander, and A. M. Aguiar, Tetrahedron Letters, 1971, 4749.

284

Organophosphorus Chemistry

Crystals of the monohydrate of the diphosphonic acid (1 64) have the PO, groups in nearly eclipsed conformations, with an approximate W arrangement of the OPCPO Co-ordination of this acid with calcium ions occurs with the formation of several types of chelate rings, two involving only phosphoryl groups and one, a five-membered chelate ring, involving an alcoholic and phosphoryl group.232 The crystal and molecular structures of the hexahydrate of disodium DL-glyceryl phosphate (165),233 adenosine 3’,5’-monopho~phate,~~~ and tetramethylamidinium phosphonate (166) 235 are also reported.

X-Ray diffraction of the phosphazene (1 67; X = 2,2’-dioxybiphenyl) When the molecular shows that all the PN bond lengths are dimensions are compared with the electronegativity of the substituents, a correlation can be made for the triniers but not the tetramers. However, correlations in both cases can be achieved if orbital electronegativities are The PN cage molecule (168) has each PNNP link planar within 80 pm. The PN bond lengths are 168 pm, in accordance with a limited ~* PN bond lengths are found in the fouramount of ~ - b o n d i n g . ~Similar membered cyclic compound (169).239 The small ring is bent by 1 l o , which is the same as that observed for the four-membered ring in the oxyphosphorane (170). The apical oxygen and phosphorus atoms of (170) were not collinear (OPO bond angle = 160°).120 The PO bond lengths 331

232 233

234

235

236

237

338

239

V. A. Uchtman and R. A. Gloss, J. Phys. Chem., 1972,76, 1298. V. A. Uchtman, J. Phys. Chem., 1972,76, 1304. R. H. Fenn and G . E. Marshall, Chem. Comm., 1971, 984. M. Sundaralingam and J. Abola, Nature New Biol., 1972, 235, 244. J. 5. Daly, J.C.S. Dalton, 1972, 1048. H. R. Allcock, M. T. Stein, and J. A. Stanko, J. Amer. Chem. SOC.,1971, 93, 3173. A. J. Wagner, J. Inorg. Nuclear Chem., 1971, 33, 3988. W. Vandoorne, G . W. Hunt, R. W. Perry, and A. W. Cordes, Inorg. Chem., 1971,10, 2591. E. H. Ibrahim, R. A. Shaw, B. C. Smith, C. T. Thakur, M. Woods, C. J. Bullen, J . S. Rutherford, P. A. Tucker, T. S. Cameron, K. D. Howlett, and C. K. Prout, Phosphorus, 1971, 1, 153.

Physical Methods Me

x x \ /

\

.//"

\

,N&P ,N--P \ Me N'

( 169)

285

'

\

N-Me

(170; Y = CF,)

indicate that there is negligible d,-p, bonding, and a similar conclusion was made for (94).lZ7 Several electron-diffraction studies have been reported. After the estimation of dihedral angles by electron diffraction, there is usually the problem remaining as to whether the estimate represents an average of many rapidly interconverting conformers or not. Thus the dihedral angle for diphosphine (139) converged to a value of 81", but this result is of doubtful significance since other angles corresponded to parameters not significantly different from that for the final refinement.24oIn the case of methoxydichlorophosphine(171) the dihedral angle probabilities, calculated from the electron diffraction measurements, were high for the range 0-27", and a dihedral angle of 17 k 6" was estimated to correspond to the real molecular conformation. The P-Cl bond length (208.4 pm) was the same as that in dimethylaminodichlorophosphine (172).241A study of Me

C1 (171)

Me,N-PCI, (172)

0 II H3CPC 1 (173)

cyanodifluorophosphine showed it to possess very similar stereochemistry to phosphorus trifluoride, and therefore it appears that the cyanide and fluoride groups have similar stereochemical effects.242 In comparison, the P-Cl bond length of the PIv dichloride (173) was 203.2 pm.243 a40 241 243 243

B. Beagley, A. R. Conrad, J. M. Freeman, J. 5. Monaghan, and B. G . Norton, J. MoE. Structure, 1972, 11, 371. V. A. Naumov, N. M. Zaripov, and V. G . Dashevskii,J . Struct. Chem., 1971,12, 135. G . C. Holywell and D. W. H. Rankin, J. MoE. Structure, 1971, 9, 11. V. A. Naumov and V. N. Semashko, J . Struct. Chem., 1971, 12, 289.

Organophosphorus Chemistry

286

8 Dipole Moments, Conductance, and Polarography Dipole moments (p) were calculated for most of the compounds studied by microwave spectroscopy (see Section 4). The P’II-N bond moment has been estimated to be 0.26 D from the dipole moments of trisdimethylaminophosphine ( p = 1.32 D) and derivatives of (174). However, it is difficult to accept that the PIV-N bond moment of the oxide of (174) is

n

0

\p”\Ph

f-7

0 0 ‘P’

still directed towards nitrogen and with increased magnitude (0.991.13 D).244The dioxaphospholan ring (175) was found to be electrondonating to halogen but electron-accepting from a methoxy-group. The dipole moments of the aryl derivatives (175; Y = Ar) indicated that a phenyl group has weak donor properties towards the ring.245 The dipole moments of a series of vinylphosphines (176; Y = MeO, R,N, Ph, or Et) have been determined. The replacement of an ethoxy-group in triethyl phosphite by a vinyl group lowers the dipole moment. The vinyl group appears to be accepting electrons from the (Et0)2P group since the introduction of electron-donating methyl groups and electron-accepting phenyl groups on the vinyl group (176; Y = OEt, R = Me or Ph) lowered and raised p, respectively. The dimethylamino and ethyl substituents on phosphorus had similar properties to an ethoxy-group. In contrast, phenyl groups on phosphorus caused the phosphorus group to accept electrons from the vinyl group.246 The bond polarities of some P-butyl and P-phenyl phospholes (177) were similar to those of acylic phosphines ( p ca. 1.5 D). This is in contrast to pyrroles and amines, which have dipole moments of ca. 2 and 1 D, respectively.247 The dipole moments of triarylphosphines decrease with the electronegativity of the para-

244

245

246

247

E. A. Ishmaeva, M. A. Pudovik, S. A. Terent’eva, and A. N. Pudovik, Dokiady Phys. Chem., 1971, 196, 63. K. S. Mingaleva, N. A. Razumova, A. A. Petrov, Z . L. Evtikhov, and F. V. Bagrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2456. K. S. Mingaleva, Y. N. Chistokletov, V. V. Kosovtzev, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 868. H. Lumbroso, D. M. Berth, and F. Mathey, Compt. rend., 1972, 274, C , 100.

Physical Methods 287 substituents, e.g. p = 1.92, 1.44, 0.65, and 0.61 for (178; Y = Me, H, C1, or F, re~pectively).~~~ Comparisons of measured and calculated dipole moments of formyl-, acyl-, and aroyl-methylenetriphenylphosphoranes(179) are discussed in relation to their conformations and charge delocalizations. The data support a predominance of the cis-forms (179) in benzene Similar comparisons for the ketophosphoryl compounds (180) indicated a predominance (ca. 90%) of the transoid conformation, as shown in (1

,c=c, ,o-

Ph,P(

H

R

o+p-C/ :j Y

R

+o

PhCH=CHPO,Et,

Similar studies have been made on the conformations of alkyl methylphenylphosphinates (131) 177 and on the stereochemistry of the cyclic phosphites (60).251987 The moment for the C(sp2)-P bond is 1.07 D, as estimated from the dipole moments of diethyl styrylphosphonate (1 8 1) and some of its The conductance of quaternary phosphonium salts 253 and diphenylphosphinic acid and its derivatives 254 has been measured, and an indirect polarographic determination of mixed phosphates and arsenates is 9 Mass Spectrometry The mass spectra of methoxydimethylphosphine (182; X = 0 ) and the corresponding sulphur compound (182; X = S) show base peaks corresponding to PO+ and MePSf respectively. Whereas the methoxyphosphine also shows a fragmentation path commencing with loss of a methoxy-group, the positive ions from the sulphur derivative show a strong tendency to

R. F. De Ketelaere, E. G. Claeys, and G. P. Van der Kelen, Bull. Soc. chim. belges, 1971, 80, 253. H. Lumbroso, C. Pigenet, A. Arcoria, and G. Scarlata, Bull. Soc. chim. France, 1971, 3838.

E. A. Ishmaeva, M. G. Zimin, R. M. Galeeva, and A. N. Pudovik, Bull. Acad. Sci.

U.S.S.R.,1971, 473.

E. E. Nifant’ev, A. A. Borisenko, I. S. Nasonovskii, and E. I. Matrosov, Doklady Chem., 1971,196,28. E. A. Ishmaeva, N. A. Bondarenko, and A. N. Pudovik, Bull. Acad. Sci. U.S.S.R., 1971, 2429.

V. M. Tsentovskii, V. P. Barabanov, F. M. Kharrasava, and T. A. Busygina, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1667. D. L. Venezky and J. E. Quick, J. Chem. and Eng. Data, 1972, 17, 23. L. Rozanski, Chem. analit., 1972, 17, 55.

288

Organophosphorus Chemistry

retain the sulphur atom.25 The fragmentation patterns of cyanophosphines showed that loss of a nitrile group is a lower energy process than loss of methoxy, dimethylamino, or phenyl.2s Examination of the spectra of a large number of acetylenic phosphines (1 83 ; R = aryl or alkyl) showed that the fragmentation pathways are strongly dependent on the nature of the

phosphorus and acetylenic s u b s t i t u e n t ~ . ~ The ~ ~ mass spectra of the phosphinoarsines (184) and (1 85) contained ions corresponding to Ph,P+ but not Ph,As+, showing that migration of phenyl to phosphorus is preferred.257 Similar migrations are observed in the spectra of the tetraphospholan (6).Ig The appearance potentials of a series of phosphine oxides (186; R = propyl, propenyl, or propynyl) are all similar to that of acetone, which supports the postulate that the predominant ionization is loss of an electron from oxygen. The fragmentation patterns were examined to see if there is a relationship with alkaline cleavage. The ion at m/e 92 is the base peak in the spectrum of (186; R = propyl) and is attributed to the 0

II Et,PR

fragmentation shown in Scheme 1. The importance of this fragmentation pathway falls for the unsaturated compounds and the rearrangement ion ( M - Et)+ rises in relative intensity. This change is attributed to a lowering of electron density at phosphorus, which stabilizes and retards the fragmentation of the anion leading to [ M - (C2Hp)2]+.258 The spectra of the phospholen oxides (187; X = RO, F, or C1) and the corresponding sulphides in general showed a predominance of heterocyclic ions and few ions resulting from loss of hydrocarbon fragments. This was attributed to the stability of the anion (188). The relative intensity (R.I.) of one such hydrocarbon fragment, C4H6+,correlated (increased) with the susceptibility to hydrolysis of the phosphorus grouping. Possible reasons for this are The relative intensity of the molecular ion of triethylphosphine sulphide is 12.4, nearly six times that of the corresponding oxide 256

257 258

25s

A. J. Carty, N. K. Hota, T. W. Ng, H. A. Patel, andT. J. O’Connor, Canad. J. Chem., 197 1,49, 2706. R. B. King and P. N. Kapoor, J. Amer. Chem. SOC.,1971, 93, 4158. G. M. Bogolyubov, V. F. Plotnikov, V. M. Ignat’ev, and B. I. Ionin, J . Gen. Chem. (U.S.S.R.), 1971, 41, 510. G. M. Bogolyubov, L. I. Zubtsova, N. N. Grishin, N. A. Razumova, and A. A. Petrov, J . Gen. Chem. (U.S.S.R.), 1971, 41, 520.

Physical Met hods

289

0

H+ II Pr -P-CH-CH, 1 Et anion 0

II

R-P-CH,CH, I Et (1 86)

o+

= Prk

-

II Pr-P-H I Et

I

0 II

& Pr-P-H I Et

+ HC-CH,

o+

II Pr-P-H

I

H m/e 92

Scheme 1

0 0 P

/ \

x o (1 87)

P

x o I\

(188)

s s

II II Et,P-PEt, (1 89)

(R.I. = 2.14). Also, the diphosphine disulphide (189) gave a (M/2)+ ion of R.I. 14.2, which is much greater than the R.I. of 1.52 for the parent diphosphine. The energy of the Prv-PIv bond was estimated from the appearance potentials of the (M/2)+ ion of the disulphide (189) and the 01 ion of triethylphosphine sulphide. Its value (2.6 eV) is lower than that (3.7 eV) of the parent diphosphine.260The dissociation energy of the P=S bond was estimated to be 3.7 eV (85 kcal mo1-1).261 The phosphepin (190) gave an abundant ion at m/e 178.262 The fragmentation involves eventual loss of H3P0, to give the ion above with a mass corresponding to that of phenanthrene. The mass spectra of some tertiary-butyl phosphoryl derivatives such as (191; Y = Cl or Ph) can be rationalized if the preferred fragmentations are loss of isobutane from the P-t-butyl groups and loss of a methyl group from the aryl-t-butyl groups.263 260

2e1 262

263

G. M. Bogolyubov, N. N. Grishin, and A. A. Petrov, J . Gen. Chem. (U.S.S.R.), 1971, 41, 817. G. V. Fridlyanskii, V. A. Pavlenko, B. A. Vinogradov, N. N. Grishin, G . M. Bogolyubov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1714. J. L. Suggs and L. D. Freedman, J . Org. Chem., 1971, 36, 2566. M. Yoshifuji, R. Okazaki, and N. Inamoto, J.C.S. Perkin I , 1972, 559.

290

Organophosphorus Chemistry

Y The mass spectra are also reported for the thiophosphates (192),264 derivatives of dimethylphosphinic acid (193),265and the phosphadiazoles (194).266 Mass spectra have been used to identify the position of l80labels in phosphinic acid derivatives 267 and to estimate the lSOcontent of inorganic phosphate after silylation.268 The molecular distance between silylated phosphate groups and/or silylated hydroxy-groups has been estimated from the abundance of the rearrangement ions (195) and (196).26a 4-

+

P(OTMS),

HOP(OTMS),

(195)

( 196)

10 pK and Thermochemical Studies The basicities of triarylphosphines (197) in chloroform-acetic acid follow an excellent Hammett correlation which includes halogen substituents. The dimethylaminophenol derivative (197; Y = Me2N) is first protonated on The pK, values of the dialkylphosphinobenzoic acids (198) suggest, rather surprisingly, that the R2P group is very weakly electronaccepting from the aryl ring; values of om = 0.10 and uD = 0.13 were

264 265 266

2G7

268

R. A. Shaw and M. Woods, Phosphorus, 1971, 1, 41. F. See1 and K. Velleman, Chem. Ber., 1971, 104, 2972. R. G. Kostyanovskii, V. G. Plekhanov, N. P. Ignotava, R. G. Bobkova, and N. I. Shvetsov-Schilovskii,Bull. Acad. Sci. U.S.S.R., 1971, 2486. R. L. Dannley, R. L. Waller, R. V. Hoffman, and R. F. Hudson, J. Org. Chem., 1972, 37,418. J. Bar-Tana, 0. Ben Zeev, G. Rose, and J. Deutsh, Biochim. Biophys. Acta, 1972, 264, 214.

269 270

D. 5. Harvey, M. G. Horning, and P. Vouros, Tetrahedron, 1971, 27, 4231. G.P. Schiemenz, Tetrahedron, 1971, 27, 3231.

Physical Methods

291

obtained.271 Acidities determined by conductance and potentiometric titrations of trichloromethyl- and phenyl-phosphonic, phenyl- and diphenyl-phosphinic, and diethyl dithiophosphoric acids are reported.272 The acidities of the thio-acids (199) were weakest and differentiated most in absolute alcohol because the change in energy of ion solvation is Ph

\

Y-P=NZ Ph'

(20 11

probably the governing From a study of the acidity and tautomerism of a di-fLketophosphonium salt it has been concluded that trans-enolization, to give (200), predominate^.^^^ The phosphinimines (201) are dibasic, with pK,'s in the range 11.5-19.4 and 5.9-9.0, but they are only monomethylated by methyl iodide.l16 The acidifying effects of phosphoryl groups on methylene and methyl protons are also Tentative bond energy values have been obtained from heats of reaction of phosphoryl Heats of reaction have been measured, using flow microcalorimetry, for the estimation of cholinesterase activity and its Free energy and enthalpy inhibition by organophosphorus changes,278heat capacities,270and distribution ratios 280 of quaternary phosphonium salts are reported. 11 Surface Properties The use of mass spectrometry as a detector in g.1.c. has the advantage that isomeric materials with the same retention times may still be distinguished, e.g. a phosphate and phosphonate.281 Mono-, di-, and tri-butyl phosphates may be separated by g.1.c. after conversion of the acidic components into their silyl esters.282A dual flame photometric detector has been described for the simultaneous determination of phosphorus-, sulphur-, and chlorinecontaining compounds. The method is based on the measurement of the 271 272

273 274 275

276 277

278

279 280

281

I. G. Malakhova, E. N. Tsvetkov, D. I. Lobanov, and M. I. Kabachnik, J . Gen. Chem. (U.S.S.R.), 1971, 41, 2837. A. Francina and A. Lamotte, Bull. SOC.chim. France, 1971, 1951. T. A. Mastryukova, L. L. Spivak, A. A. Grigor'eva, E. K. Urzhuntseva, and M. I. Kabachnik, J . Gen. Chem. (U.S.S.R.), 1971, 41, 1953. T. A. Mastryukova, V. Rubashevskaya, I. M. Aladzheva, and M. I. Kabachnik, J . Gen. Chem. (U.S.S.R.), 1971, 41, 2358. E. S. Petrov, E. N. Tsvetkov, M. I. Kabachnik, and A. I. Shatenshtein, J. Gen. Chem. (U.S.S.R.), 1971, 41, 1173. A. S. Kertes, J. Inorg. Nuclear Chem., 1972, 34, 796. J. Konickova and I. Wadsoe, Acta Chem. Scand., 1971, 25, 2360. D. H. Berne and 0. Popovych, J. Chem. and Eng. Data, 1972, 17, 178. R. K. Mohanty and J. C. Ahluwalia, J. Chem. Thermodyn., 1972, 4, 53. N. A. Gibson and D. C. Weatherburn, Analyt. Chim. Acta, 1972, 58, 149. C. B. C. Boyce and S. B. Webb, J . Chem. SOC.(C), 1971, 3987. J. W. Boyden and M. Clift, Z . analyt. Chem., 1971, 256, 351.

292

Organophosphorus Chemistry

emission bands of HPO and S , at 526 and 394 nm and of indium chloride at 360 nni, the indium chloride being formed by passing the vapour over indium metal.2aa Similar methods have been developed for specific pesticides,2s4and an inexpensive gas chromatograph for the determination and collection of labile organophosphorus compounds has been described.285 Many methods are now available for the chromatographic separation of polar compounds. Further work is reported on the high-pressure pellicular anion-exchange chromatographic separation of adenosine derivatives,2ss and the pH dependence of the anion-exchange chromatographic separation of tri- and tetra-phosphates has been clarified.287 Thin-layer chromatographic separation of a vinyl phosphate 288 and a dithiolate 289 and paper chromatography of phosphonates 290 have been reported. Gel chromatography, which depends primarily on molecular weight differences, has been used (a) to separate mono-, di-, and tri-alkylated phosphates 291 and (b) for the estimation of organic phosphates in It is interesting to note a reversal of roles; tri-n-octylphosphine oxidetreated cellulose has successfully separated gold, antimony, and thallium.293

12 Radiochemical Studies A non-destructive and rapid (6-8 min) determination of phosphorus and sodium in organophosphorus compounds may be achieved by fast A rapid method of determining 32P and 33P in neutron aqueous solution utilizes a combination of Cerenkov radiation counting and liquid scintillation counting.205 Adsorption on charcoal before scintillation counting of 32Phas also been used.2D6 283 284

285 28E

287

B. Versino and G. Rossi, Chromatographia, 1971, 4, 331. M. C. Bowman and M. Beroza, J. Assoc. Ofic.Analyt. Chemists, 1971, 54, 1086; M. C. Ivey and H. V. Claborn, J . Agric. Food Chem., 1971, 19, 1256. A. F. Machin and C. R. Morris, Analyst, 1972, 97, 289. G. Brooker, J . Biol. Chem., 1971,246, 7810; S . N. Pennington, Analyt. Chem., 1971, 43, 1701 ; H. W. Shmukler, J. Chromatog. Sci., 1972, 10, 137. T. Nakamura, M. Kimura, H. Waki, and S. Ohoshi, BUN. Chem. SOC.Japan, 1971, 44, 1302.

288 289 290

291 292

293 294

295 290

M. Kotakemori and A. Kawagisi, Japan Analyst, 1971, 20, 709. A. Murano and M. Nagase, Japan Analyst, 1971, 20, 665. W. E. Roop, S. A. Tan, and B. L. Roop, Analyt. Biochem., 1971, 44, 77. H. Tanaka and K. Konishi, J. Chromatog., 1971, 60, 430. J. H. Steward and M. E. Tate, J. Chromatog., 1971, 60, 75. J. Blouri and G. Revel, J. Radioanalyt. Chem., 1972, 10, 121. I. P. Lisovskii and L. A. Smakhtin, J. Radioanalyt. Chem., 1971, 8, 75. L. C. Brown, Analyt. Chem., 1971, 43, 1326. T. Chojnacki and Z. Matysiak, Analyt. Biochem., 1971, 44, 297.

Author Index Abola, J., 284 Abramov, V. S., 109 Absar, I., 187, 278, 279 Abul'khanov, A. G., 238 Adam, W., 245 Aganov, A. V., 82, 269 Agarwal, K. L., 153 Agawa, T., 185 Aguiar, A. M., 82,130,131, 283 Ahluwalia, J. C., 291 Ahmad, M., 151 Ahmed, F. R., 235 Akamsin, V. D., 54 Akiba, K., 22, 183, 245 Akintobi, T., 192 Akiyama, S., 196 Aksenov, V. I., 127 Aladzheva, I. M., 17, 23, 29 1 Alam, S. S., 159 Albanbauer, J., 91, 177 Al'bitskaya, V. M., 49 Albracht, S . P. J., 274 Albrand, J. P., 271 Albridge, R. G., 280 Alekandrova, N. A., 88 Alfonskaya. L. S., 77 Ali, A., i92 Alimov, M. P., 125 Alimov, P. I., 125 Allcock. H. R.. 49. 224, 228, 23 1, 235,274, ' 284 Allcox, I. L., 257 Allen, C. W., 232 Allen, D. W., 6, 19, 33, 251 Allen, G. W., 171 Allen, L. C., 29, 259 Amidou, A. B., 225 Amos, H., 158 Anderson, A. G., 68 Anderson, D. R., 250 Andreae, S., 136 Andrewes, A. G., 195 Andrews, G. C., 106 Aneja, R., 8, 170, 246 Anfinsen, C. B., 143 Ang, H. G., 1 Angelmo, N., 160 Ankel, H., 159 Annan, W. D., 172 Anoshina, N. F., 7 Anschel, M., 77 Anschutz, W., 84 Ansell, G. B., 235 Anstey, R. H., 229 Anthony, R. S., 172

Appel, R., 9, 10, 203, 210, 21 1. Apprion, P., 128 Arbuzov, B. A., 42, 46, 55, 56, 57, 90, 94, 96, 275 Archibald, R. M., 277 Arcoria, A,, 102, 287 Armsen, R., 178 Armstrong, D. R., 224 Asano, K., 258 Ash, A. B., 140 Ashe, A. J., 24, 279 Ashkinadze, L. D., 275 Aspinall, G. O., 160 Auschutz, W., 138 Avigad, G., 168 Aviv, H., 157 Awerbouch, O., 74 Axelrod, E. H., 194 Azzaro, M., 142 Babcock, D., 151, 152 Babler, J. H., 201 Babyak, A. G., 213 Baechler, R. D., 13, 71, 26 3 Bauerlein, E., 166, 167 Bagrov, F. V., 41, 286 Bakakhontseva, V. N., 168 Balasubramanian, S., 110 Bald, R. W., 143, 149 Baldwin, J. E., 177, 246 Ballantyne, W., 151 Banks, G. R., 156 Barabanov, V. P., 287 Baranov, G. M., 275 Baranov, S. N., 87, 129 Baranovskii, L. A., 127 Baranowski, T., 160 Barber, M., 51, 281 Barker, R., 168 Barker, R. W., 171, 271 Barley, G. C., 195 Barr, R. M., 159 Barrans, J., 48, 104 Bar-Tana, J., 290 Bartish, C. M., 116 Barton, D. H. R., 120,236, 246 Bartsch, W., 199 Barycki, J., 87 Bashirova, L. A., 69 Bassett, P. J., 51, 281 Baudler, M., 2, 3, 71, 253 Bauer, B. J., 143 Bauer, G., 212, 237 Bauer, R. J., 147

293

Bauerlein, E., 119 Baukov, Yu. I., 99 Beagley, B., 285 Bebikh, G. F., 211 Beck, D. R., 281 Beck, P., 84 Begtrup, M., 269 Begum, A., 51, 239, 272 Behrens, N. H., 159 Beikirch, H., 156 Bell, J. D., 171, 271 Beloglazova, T. N., 233 Bel'skii, I. F., 56, 69 Belskii, V. E., 125, 135 Belyaev, N. N., 183 Belyaev, Yu. P., 225 Bender, M. L., 174 Benezra, C., 138, 242, 269 Benkovic, S. J., 125, 168 Benrens, N. H., 159 Benschop, H. P., 137 Bensoam, J., 33 Bentlev. T. J.. 120. 236 Bentnide, W: G.,' 41, 47, 48, 74, 101, 141, 237, 257,264, 270, 272, 275 Ben Zeev, O., 290 Berden, J. A., 274 Bergelson. L. D.. 170 Berger, HI, 122 ' Bergerhoff, G., 265 Bergesen, K., 89, 141 Bergmann, E. D., 200 Berlin, K. D., 16, 18, 270, 28 1 Bermann. M.. 64. 214. 220 Bernard, D., 39, 42, 43, _

48.49

,

I

Ber;lk,-D. H., 291 Berninger, C. J., 180 Beroza, M., 292 Bertazzoni, U., 158 Bertin, D. M., 286 Bertrand, R. D., 141, 267 Beslier, L., 44 Bestmann, H. J., 18, 176, 178, 195, 196 Bezzubova, N. N., 135 Bhacca, N. S., 65 Bhalerao, U. T., 194 Bianchini, J. P., 88 Biddlestone, M., 231 Bieniek. T.,233 Bigorgne, M.,112 Bilofsky, H. S., 30 Binder, H., 65, 215, 222, 223 Bindra, A. P., 198

Author Index Binsch, G., 259 Birdsall, W. J., 224, 274 Birnboim, H., 158 Bishop, J. K. B., 51, 272 Bishop, M. J., 167 Bissell, E. C., 49 Blackburn, G. M., 254 Blagoveshchenskii, V. S., 118 Blanchard, C., 140 Blaser, B., 203, 210 Block, H. D., 120 Blouri, J., 292 Blumbergs, P., 140 Blumenstein, M., 256 Bobkova, R. G., 290 Bodalski, R., 89, 132 Bodnarchuk, N. D., 207, 214 Bohler, D., 226 Boehm, W., 187 Boehne, H., 3 Bogatskii, A. V., 88 Bogolyubov, G. M., 73, 74, 288, 289 Bohlmann, F., 195 Boisdon, M. T., 114 Bokanov, A. I., 279 Boldeskul, I. E., 275 Bondarenko, N. A., 287 Bondarenko, V. M., 225 Bondinell, W. E., 163, 194 Bonnafous, J. C., 195 Bonte, B., 13 BODD.T. T.. 261

Borowitz, G. B., 102 Borowitz, I. J., 10, 77, 102, 103,257 . . Borsus, J.-M., 185 Both, W., 196 Bouquet, G., 112 Bowman, M. C., 292 Boyce, C. B. C., 61, 129, 238, 291 Boyden, J. W., 291 Bragin, J., 276 Brain, E. G., 182 Bram. G. M.. 162 Brass; H. J., 134 Braun, H., 1, 15 Braye, E. H., 27, 239 Breen, J. J., 256, 282 Brelivet, J., 128 Brentnall, H. J., 143 Breslow, R., 172 Bridger, W. A., 172 Bright, H. J., 161 Brittain, A. H., 52, 279 Britton, R. W., 195 Brocas, J., 31 Bromilow, R. H., 122, 123 Brooker, G., 292 Broquet, C., 185 Brown, C., 101, 102 '

Brown, D. H., 160 Brown, D. M., 156 Brown, G. M., 117 Brown, J. N., 283 Brown, L. C., 292 Brownsey, R. W., 169 Briimmer, W., 143 Bruenner, H. U., 3 Brun, G., 140 Brunswick, D. J., 148 Brunt, C., 157 Brunt, R. V., 169 Bryan, P. S., 278 Brzezinski, J., 280 Buchanan, J. G., 169 Buchi, G., 15 Buchowicz, J., 149 Buck, H. M., 49, 240 Budovskii, E. I., 143, 149 Biichi, G., 182 Bugerenko, E. F., 127 Bugianesi, R. L., 158 Bullen, G. J., 235, 284 Bundgaard, T., 267 Bunton, C. A., 121 Buono, G., 42, 96 Burg, A. B., 71 Burgada, R., 39, 42, 43, 48, 49, 109, 261, 277 Burger, K., 44,91, 98, 177, 243 Burgers, P. M. J., 154 Burkhardt, J., 233 Burkhardt, T., 195 Burmakina, T. V., 57 Burnaeva, L. A., 37 Burns, P., 87, 136 Burt, D. W., 107 Burtsev, V. A., 90 Bushweller, C. H., 30 Busygina, T. A., 287 Butcher, R. W., 143 Butova, T. D., 88 Byrne, J. E., 71 Cadogan, J. I. G., 48, 133, 248 Calderazzo, F., 258 Callot. H. J.. 138. 242. 269 ' Cama, L. D., 166 Cameron, A. F., 204, 235, 283 Cameron, T. S., 73, 284 Camiener, G. W., 162 Campagnari, F., 158 Cann, P. F., 82, 83 Capka, M., 2 Caplier, I., 27, 239 Capozzi, G., 87, 135, 136 Carey, F. A., 268 Carnduff, J., 65 Carrie, R., 185, 200 Carriuolo, J., 151 Carty, A. J., 2, 288 Casev. J. P.. 71 Cashki, M.,'152 Cashion, P. J., 153 Casper, E. W. R., 103, 257 Casper, J. M., 276 I

,

_

Cassidy, F., 182 Castro. B.. 9. 18, 246 Caughlan,'C. N., 35, 43, 268, 270 Cavell, R. G., 275 Cawley, T. N., 169 Cernv. M.. 2 Chadha, J: S., 170 Challis, J. A., 133 Chan, T. H., 79 Chang, B. C., 32, 44, 49, 255 Chang, T.-H., 207, 215 Charrier, C., 261 Chasle, M.-F., 8 Chatta, M. S., 130, 131 Chatzidakis, A., 27, 244 Chekhmakheva, 0. G., 153 Chemodanova, L. A., 77 Chen, C. H., 16, 67, 281 Chenault, J., 120 Chenery, D. H., 153 Cherkasov, R. A., 276 Chernyshev, E. A., 127 Chikamune, O., 129 Chirkunova, S. K., 69 Chistokletov. V. N., 16,93. 256, 286 Chivers, T., 228, 232 Chladek, S., 151 Chojnacki, T., 292 Chong, K. J., 117, 145 Chone. R.. 192 ChourJ. Y . , 156 Christensen, B. G., 166 Christiansen, G. D., 183 Christol, H., 5 Christophliemk, P., 142 Churchman, R., 28, 274 Claborn, H. V., 292 Claeys, E. G., 287 Clardy, J. C., 267, 282 Clare, P., 226 Clarke, F. B., 27, 131 Clifford, D. B., 182 Clift, M., 291 Clipsham, R. M., 219, 224 Clive, D. L. J., 246 Coates, R. M., 174 Cochrane, J. S., 195 Coerdeler, J., 9 Coffinet. D.. 180 Cogne, A., 271 Cohen, J. S., 254 Cohn, K., 52, 63, 72, 279 Cohn, M., 171 Colbv. T. H.. 118 Collihgton, E. W., 195 Combret, J.-C., 8 Cone, J., 174 Connor, J. A., 51, 281 Conrad, A. R., 285 Conrad, W. E., 32, 255 Cook, A. F., 151 Cook, A. G., 59 Cook, R. J., 71 Cooke, R., 152 Cookson, R. C., 77 Cooper, C. M., 246 ,

,

Author Index Cooperman, B. S., 123, 148 Coppola, J. C., 7, 153 Cordes, A. W., 284 Corfield, J. R., 53, 74, 137, 258 Cori. C. F.. 160 Corre, E., 41 Corrie, J. E. T., 189 Coskran, K. J., 54, 253 Costisella, B., 140 Cosvn. J. P.. 196 Cotion, F. A., 220 Cottrell, I. W., 160 Coulson, C. A., 51 Couret, C., 39, 72 Court, A. S., 268 Cowley, A. H., 31, 63, 27 1 Cox, P. J., 182 Craig, D. P., 223 Cramer, F., 145, 147 Craven, S. M., 276 Crea, J., 258 Creasy, W. S., 23, 42, 191, 254 Cremer, H.-D., 198 Cremer, S. E., 74, 267 Cremlyn, R. J. W., 118, 119 Cresp, T. M., 199 Crim, F. F., 182 Cristau, H.-J., 1, 5 Cronan, J. E., jun., 171 Crosscup, C. J., 154 Crouch, R. K., 10, 103, 257 Crouse, D. M., 19, 178, 180 Crowder, R. D., 162 Cuatrecasas, P., 143 Cuddy, B. D., 74, 258 Cullen, W. R., 51, 272 Cummerson, D. A., 169 Curci, R., 81, 106, 246 Cusachs, L. C., 29, 259 Cushley, R. J., 250 Dahl, J., 65 Dahl, O., 8 Dale, S. W., 271 Daly, J. J., 284 Damerau, W., 273 Daniewski, W. M., 61 Danion, D., 200 Danks, L. J., 15, 241 Dannley, R. L., 86, 137, 243, 290. Dashevskii, V. G., 285 Davidson, N., 158 Davies, A. G., 236, 272, 273 Davies, A. P., 8, 246 Davies, M., 187 Davies, P. B., 278 Davis, M. I., 235 Davis, R. A., 180 Dawson, J. W., 2 Dawson, T. M., 246

295 Day, A. C., 195 Dean, P. D. G., 162 De’ath, N. J., 34, 65, 107, 246, 255, 260, 261 De Bruin, K. E., 139, 271 Degarry, N., 127 Degterev, E. V., 125 Deguchi, Y., 274 De Ketelaere, R. F., 287 Deljac, A., 195 Delpuech, J. J., 258 De Luca, U., 158 de Maine, M. M., 168 Demersemen, B., 112 De Montellano, P. R. O., 97

Denney, D. B., 31, 32, 34, 49, 65, 107, 245, 246, 255. 260. 261 Denney, D.Z.; 31, 32, 34, 65. 245. 246. 255. 260. 261 . . . Denyer, C. V., 246 Depoorter, H., 187 Derkach, G. I., 103, 207, 209. 210 Descroix, H., 280 Deutsch, J., 290 Devanneaux, J., 224 Deventhal, J., 141 Devlin, C. J., 177, 262 de Waal, W., 195 Dewhurst, B. B., 118, 119 Dianova, E. N., 42, 96 Dieck, R. L., 207, 225 Diehl, J. W., 245 Diemert, K., 132 Dietsche, W., 57 Di Furia, F., 81, 106, 246 Dillon, K. B., 251 Dimroth, K., 24, 25, 26, 27, 240, 244, 269 di Sanseverino, L. R., 153 Distler, W., 178 Dixon, J., 246 Dmitrieva, G. V., 60 Doak, G. O., 39 Dobbie, R. C., 61 Dodonov, A. M., 61 Dogadina, A. V., 131, 254 Dombrovskii, A. V., 10, 177, 187, 190 Donini, P., 152 Donohue, J., 137 Dormoy, J.-R., 9, 246 Dorokhova, V. V., 75 Doroshenko, V. V., 70 Doyle, M., 196 Drach, B. S., 127, 215 Drake, G. L., 3 Dreiman, N. A., 233 Drew, M., 120 Drozd, G. I., 52, 64 Druce, P. M., 60 Druet, B., 13 Duesler, E. N., 283 Duwel, H., 198 Duff, R. E., 33,260 Duke, J., 152 ’

Dulog, L., 61, 238 Dumas, L. B., 156 Dunham. L.. 202 Dunmur; R: E., 37, 216, 26 1 Duprk, M., 178 Durig, J. R., 276 Dyadyusha, G. G., 224 D’yakonov, A. I., 49 D’yakonova, N. I., 61 D’yakov, V. M., 101, 277 D’yakova, T. L., 101, 277 Eastlick, D. T., 133 Ebeling, J., 221 Ebert, H.-D., 13, 78 Ecker, A., 132, 241 Eckes, H., 84 Eckstein, F., 144, 151, 152 Eckstein, U., 138 Edelman, R., 32, 255 Edlin, G., 152 Edmond, J. G., 174 Edmonds, M., 157 Edmundson, R. S., 89, 109, 119 Edwards, J. O., 134 Egan, W., 27, 263 Egorov, Yu. P., 218, 219, 275 Eguchi, M., 12, 117 Ehrlich, J., 160, 161 Eichelberger, J. L., 85 Eiki, T., 122 Eisenhut, M., 39, 63, 261 Elegant, L., 142 Elepina, L. T., 168 Eliel, E. L., 259 Eliseenkova, R. M., 54 Elisenkov, V. N., 135 Elix, J. A., 198 Elliott, W. N., 280 Ellis, K., 133 El’natanov, Y. I., 3 Emsley, J., 205 Emsley, J. W., 252 Engel, R., 271 Engelhardt, G., 72, 253 Englard, S., 168 Englund, P. T., 157 Epshtein, L. M., 275 Epstein, J., 135 Epstein, W. W., 174 Erlich, H., 152 Erman, W. F., 194 Ermolaeva, M. V., 135 Ernazarov, M., 56 Escudie, J., 39, 72 Etienne, A., 13 Evans, D. A., 106 Evans, P. J., 159 Everett, J. W., 246 Everett, M. E., 280 Evtikhov, Zh. L., 37, 96, 286 Faerber, P., 144 Fahmy, M. H., 124

296

Author Index

Failli, A., 207, 215 Faizullin, E. M., 56 Falke, J., 265 Fang, K. N., 147, 271 Fanta. W. I.. 194 Farnham, W. B., 177

Faiild, H., 148 Faucher, J. P., 224 Faught. 5. B.. 235 Fearherman, S. I., 256 Feeney, J., 252 Fehn, J., 44, 91, 98, 177, 243 Feldmann, R., 198 Fenn, R. H., 284 Feshchenko, N. G., 54, 68 Fil$,-M., 31, 63, 258, 274, LI I

Fina, N. J., 134 Finkenbine, J. R., 79 Firestone. R. A.. 166 Firstenb&g, S., ' 102, 103, 967

Fi&%, H. U., 148 Fischer, D., 157 Fischer, L. V., 147 Fisichella. S.. 102 Flaskerud, G., 226 Fleming, R. H., 177 Flitsch, W., 183 Florey, J. B., 29, 259 Floyd, A. J., 77 Fluck, E., 207, 215 Foester, R., 63, 72 Fondy, T. P., 169 Forrest, H. S., 174 Fottrell, P. F., 161 Foucaud, A., 8, 41, 201 Fouquet, G., 177 Fouquey, C., 141 Fox, W. B., 63, 72 Frampton, R. D., 125 Francina, A., 291 Frank, A. W., 3 Fray, G. I., 77 Freedman, L. D., 16, 81, 130, 251, 289 Freeman, B. H., 188 Freeman, J. M., 285 Freenor,-F. J., 68 Freist, W., 145 Fridkin, M., 156 Fridland. S. V.. 69 Fridlyanskii, G: V., 289 Frjedl, J., 91, 177 Fritsch, W., 202 Fritz, G., 71 Fritzowsky, N., 52, 277 Frolova. T. I.. 82

42, 94,

Gabbai, A., 152 Gabriel, T. F., 157 Gadreau, C., 201 Gagnaire, D., 271 Gaidamaka, S. N.. 215. 216 Gal, J.-Y., 240 Galakhov, I. V., 254 Galan, M., 280 Galeeva. R. M.. 77. 287 Gallacher, M. J., 77 Gallant, J., 152 Garbers, C. F., 15, 189, 254 Gareev, R. D., 82, 269 Garratt,P. J., 196,198,199, 246 Garrigues, B., 43, 271 Gates, P. N., 251 Gautzdamaka, C. T., 139 Gazizov, M. B., 87 Gazizov, T. Kh., 90 Gelbeland, K., 13 Geider, K., 143 Gelbaum, L., 271 Genkina, G. K., 103, 142 Geoffroy, M., 272 Georgiev, V. I., 254 Germa, H., 109 Gerry, M. C. L., 51 Ghangas, G. S., 169 Gibson, N. A., 291 Gielen, M., 31 Gilham, P. T., 156, 158 Gilje, J. W., 52, 261 Gillespie, P., 29, 259 Gilyarov, V. A., 103, 145, 218,219, 275 Gitel', P. O., 230 Glemser, O., 3, 222 Glonek, T., 166, 251 Gloss, R. A., 284 Goddard, N., 255, 265 Gorgen, F., 210 Goetz, H., 23, 218, 252 Goldberg, S. Z., 283 Gol'dfarb, E. I., 57 Goldman, R., 143 Goldschmidt, J. M. E., 227, 228 Golik, G. A., 210 Gombler, W., 53, 110, 268 Gonzalez-Porque, P., 161 Goodman, L., 147 Goody, R. S., 152 Gorak, R. D., 128 Gorbatemko, Zh, K., 54 Gordon, M., 61 Gorenstein, D. G., 80, 121 Gorzny, K., 90 Goubeau, J., 52,277 Gough, S. T. D., 109 Gozman, I. P., 39, 238, 273 Grace, D. S. B., 48, 248 Graf, R., 199 Graf, U., 195 Gramze, R., 271 Granoth, I., 24, 59, 73 ~~

Grapov, A. F., 133 Graves, G. E., 205 Gravestock, M. B., 194 Gray, G. A., 74, 256, 267 Gray, G. R., 168, 250 Gray, H. B., 279 Gray, R. W., 192 Greber, G., 233 Grechkin, E. F., 1, 75, 76 Grechkin, N. P., 38, 265 Green, B., 226, 227 Greenwald, J., 243 Griffin, C. E., 61 Grigor'eva, A. A., 291 Griller, D., 236, 273 Griller, D. D., 272 Grimm, L. F., 205, 212, 265 Grinblat, M. P., 219 Grishin, N. N., 74, 288, 289 Grobe, J., 4 Groen, M. B., 190 Gross, H., 140 Grosse-Bowing, W., 212, 213 Grossman, L., 156 Gruenwedel, D. W., 158 Grushko, I. E., 69 Gryzlova, G. K., 231 Gubanova, G. S., 38 Gubnitskaya, E. S., 207 Guchhait. R. B., 164 Giinther, .H., 198 GuCron, M., 158, 251 Guest, M. F., 51, 277, 281 Guibe-Jampel, E., 118 Guilford. H.. 148. 162 Gulick, W. M.,240, 274 Gulyaev, N. N., 145 Gunther, H., 269 Gurny, R., 199 Guroff, G., 174 Gur'yanova, I. V., 7, 37, 27 5 Gusakova, G. S., 101, 277 Guskova, L. I., 149 Gutzchebauch, K., 131 Gymer, G. E., 77 Haag, A., 13 Haake, P., 87, 135, 136, 171 Haas, K., 226 Haede, W., 202 Hafferl, W., 202 Hair, N. J., 204, 235, 283 Hall, C. D., 6, 31, 188, 241, 245, 260 Halmann, M., 243, 280 Hamada, A., 6, 189 Hamilton, W. C.. 283 Hammes,-O., 265 Hampl, J., 226 Han, S. C. H., 170 Hancock. A. J.. 264 Hansen, E. R.,'237 Hansen, R. S., 267 Hanson, J. R., 195 Hanson, K. R., 163

Author Index Harman, J. S., 64 Harpp, D. N., 41 Harrjs, R. K., 37, 216, 261 Harris, R. O., 224 Harrison. D. G.. 72 Harrison; P. G.,'266, 268 Harrison, W., 235 Harshman, R. B., 152 Hart, R. M., 272 Hartman, F. C., 173 Hartsuiker, G. J., 235 Hartzler, H. D., 192 Harvey, C. L., 157 Harvey, D. J., 290 Harwood, H. J., 76 Hashimoto, M., 117, 246 Hassan, B. E. M., 129 Hassid, W. Z., 158 Hata, T., 47, 117, 145, 155, 254 Hattaha, T., 1 Hattori, M., 155 Haubold, W., 215 Haussmann, P., 233 Havlicek, M. D., 261 Hayase, Y.,194 Hayashi, T., 224, 233 Hayatsu, H., 153 Hazai, I., 149 Heathcote, C., 280 Heck, K., 141 Hedgeland, R., 228 Heimer, E. P., 151 Heine, H. W., 183 Heitz, W., 176 Hellwinkel, D., 46 Helmreich, E., 160, 161 Hemming, F. W., 159 Henderson, T. O., 166,251 Hendrickson, D. N., 280 Herberg, K., 98 Hercules, D.-M., 254 Herr, M. E., 65 Herriott, A. W., 138, 183 Hesse, R. H., 120, 236 Hetflejs, J., 2 Hettche, A., 25, 240, 269 Hettler, H., 147 Hewitt, G., 246 Hewson, M. J. C., 30, 31, 63, 64, 258, 261 Heyns, K., 154 Hiatt, R., 13, 245 Hickey, M. E., 172 Higashi, F., 114 Hilbert, P., 84 Hilderbrand, R. L., 166, 25 1 Hillier, B., 282 Hillier, I. H., 51, 277, 28 1 Hin, B. C., 28 Hirayama, Y., 1 Hoare, D. S., 174 Hobbs, J., 144 Hobbs, M. E., 271 Hofle, G., 246 Hoffman, R. V., 86, 137, 243, 290 Hoffmann, P., 29, 259

297 Hoffmann, R., 29, 64, 259 Hogness, D. S., 159 Holah, D. G., 28, 274 Hollander, J. M., 280 Holman, M. J., 151 Holmes, A. B., 198, 199 Holmes R. R., 274 277 Holy, 120, 145, 145, 149 Holywell, G. C., 285 Homer, G. D., 79 Honda, H., 145 Horiguchi, M., 165 Horn, H. G., 216, 252, 267 Horner, L.,18, 84 Homing, M. G., 290 Horspool, W. M., 84, 104 Hota, N. K., 2, 224, 288 Houalla, D., 38, 44 Hovanec, J. W., 173 Howe, R. K., 190,257 Howell, J. M., 29, 64, 259 Howells, D., 82, 83 Howlett, K. D., 284 Hudson, H. R., 88 Hudson, R. F., 86, 101, 102, 112, 125, 137, 243,

A.,

290

Hinig, S., 190 Hueske, E. E., 12 Hughes, A. N., 28, 187, 274 Hugl, E., 22, 189 Hui, B. C., 274 Hulla, F. W., 148 Humphrey, R. E., 12 Hung, A., 52,261 Hungerford, L., 73 Hunt, G. W., 284 Hunter, F. E., jun., 167 Huntley, B. G., 19 Hutchins, R. O., 113 Hutchinson, D. W., 143, 162 Hutley, B. G., 33, 251 Ibanez, J. D., 146 Ibrahim, E. H., 284 Ignat'ev, V. M., 73, 288 Ignatova, N. P., 267, 290 Ikehara, M., 119, 145, 153, 155, 156, 282 Il'ina, N. A., 109 Illingworth, B., 160 Il'yasov, A. V., 273 Inamoto, N., 22, 59, 183, 241, 245, 289 Ingold, K. U., 236, 274 Ionin, B. I., 73, 131, 254, 256, 288 Irvine, I., 271 Isaacs, N. S., 8, 66, 246 Isaacs, N. W., 153 Ishizo, H., 122 Ishmaeva, E. A., 77, 276, 286,. 287 Ismagilova, N. M., 52 Ismailov, V. M., 132, 269

Isoe, S., 194 Issleib, K., 3, 4, 7, 78 Itakura, K., 121, 155 Ivanov, B. E., 87, 96, 238 Ivanovskaya, K. H., 57 Ivey, M. C., 292 Ivin, S. Z., 52, 64 Iwashima, A., 162 Iwata, K., 187 Iwata, T., 282 Izawa, O., 175 Jacobson, R. A., 282 Jacques, J., 141 Jaenicke, L.,192 JagodiC, V., 92 Jahns, H.-J., 10, 108 Jakobsen, H. J., 256, 267, 269 Jampel, E., 145 Janik, B., 144 Janssen, E., 225 Janzen, A. F., 136 Jastorff, B., 145, 147 Jencks, W. P., 151 Jenkins, I. D., 77 Jenkins, R. N., 16 Jennings, W. B., 74, 261 Johnson, A. W., 203 Johnson, D. M., 139, 271 Johnson, R. A., 65 Johnson, W. D., 41, 47, 48, 101, 264,275 Johnson, W. S.. 194 Johnston, J. A.; 182 Jolly, W. L., 280 Jones, C. E., 54, 253 Jones, E. R. H., 195 Jones. 5. B.. 182 Jouany, C.,'266 Juds, H., 23 Jugelt, W., 136 Jugie, G., 266 Sung, P., 159 Junkes, P., 3, 253 JuriSek, L., 172 Juvale, C., 157 Kabachnik, M. I., 17, 23, 73,89,103,139,141,145, 218. 219.275. 291 Kabachnik, M.'M., 153 Kainosho, M., 264 Kajiwara, M., 230 Kakurina, V. P., 7 Kalabina, A. V., 75 Kalbacher, B., 152 Kalenskaya, A. I., 208 Kalinin, A. V., 185 Kamai, G. Kh., 52, 56, 57, 58, 69 Kamego, A., 121 Kanai, Y.,145 Kanematsu, K., 11, 241 Kano, T., 4 . Kanter, H., 25 Kapoor, P. N., 4, 288 Kapuler, A. M., 152

Author Index

298 Karimullina, E. Kh., 37 Kashman, Y., 13, 74, 110 Kataeva, V. A., 69 Katchalski, K., 143 Kates, J., 157 Kates, M., 264 Kato, T., 144 Katz, I., 172 Katz, T. J., 30, 46 Katzman, S. M., 93, 247 Kaufmann, G., 156 Kawagisi, A., 292 Kawamoto, I., 47, 254 Kazitsyna, L. A., 275 Kazymov, A. V., 23, 187 Keat, R., 265, 271 Keller, T., 269 Kemp, W., 196 Kennard, O., 7, 153 Kenyon, G. L., 74, 162 Kerek, F., 79, 281 Kerr, C. M. L., 239 Kerr, K. A., 153 Kertes, A. S., 291 Kessel, A. Y., 138 Kessenikh, A. V., 265, 267 Kessler, H., 259 Kettler, M., 151 Khachaturyan, 0. B., 224 Khaddar, M. R., 258 Khaikin, L. S., 282 Khairullin, R. S., 57, 58 Khairullin, V. K., 60, 138 Khalaturnik, M. V., 190 Khalitov, F. G., 276 Khan, S. A., 123 Khan, W. A., 41, 47, 101, 237, 264, 275 Kharrasava, F. M., 287 Khasawinah, A., 124 Khim, C. S., 189 Khomenko, D. P., 224 Khorana, H. G., 153 Khusainova, N. G., 82 Khwaja, T. A., 118, 145 Kifer, E. W., 69 Kilcast, D., 28, 74, 239, 273 Kim, C. S., 19, 21, 269 Kim, Y.-H., 154 Kimball, A. P., 146 Kimura, M., 292 King, J. F., 15, 241 King, R. B., 4, 288 King, R. R., 192 Kirby, A. J., 122, 123, 153 Kireev, V. V., 219, 230, 233 Kirilov, M., 141, 199 Kirizlova, K. M., 187 Kirkpatrick, D., 8, 66, 246 Kirkwood, S., 159 Kirsanov, A. V., 54, 68, 70, 127, 207, 209, 210, 214, 216, 217 Kishida, Y., 47, 254 Kislitsyna, N. M., 99 Kitos, P. A., 158

Kiuchi, K., 183 Kjmen, H., 195 Klebanskii, A. L., 219 Kleinschuster, J. J., 168 Kleinstuck, R., 9, 10, 203, 210,211 Klemperer, W., 278 Klingebiel, U., 222 Klingenfuss, M., 166 Kluba, K., 117 Kluger, R., 163 Klusacek, H., 29 Klusacek, K., 259 Knorre, D. G., 153 Knowles, P. F., 163 Knunyants, I. L., 135, 254 Kobayashi, E., 225, 233 Kobes, R. D., 173 Kochetkov, N. K., 143, 149. Koenig, M., 38, 43, 271 Kosinskaya, I. M., 127, 209 Kosovetsev, V. V., 16,256, 286 Kossel, H., 157 Koster, H., 154 Kottgen, D., 52 Kohl, H., 202 Kolesnik, A. A., 88 Kolesnikov, G. I., 90 Kolesnikov, G. S., 219, 230, 233 Kolesnikova, N. A., 128 Kolodyazhzyi, O., 1, 2, 15 Komatsu, M., 185 Komlev, I. V., 115 Kondo, K., 90 Kondo, N. S., 147, 271 Kondratenko, V. I., 207, 213 Konishi, K., 292 Konickova, J., 291 Konotopova, S. P., 93 Koop, H., 69 Kopay, C. M., 21 Kornberg, R. D., 171 Kornuta, P. P., 208 Korolev, B. A., 142, 218 Korytnyk, W., 160 Kosrov, E. S., 139 Kostikin, L. I., 230 Kostyanovskii, R. G., 3, 290 Kostyuk, A. S., 99 Kotakemori, M., 292 Kotick, M. P., 144 Kotlyar, N. G., 206 Kotovich. B. P.. 128 Kovtun, V. Yu.; 218, 275 Koyama, T., 175 Kozlov, E. S., 127, 215, 216. 224 Kozlova, L. N., 90 Kozuka, S., 112, 247 Kraemer, R., 141, 270 Kraihanzel, C. S., 116 Kranz, E., 18 Krasil’nikova, E. A., 54, 77, 87

Kraus, J., 126 Krawiecka, B., 141, 271 Kreiser, T. H., 144 Kren, R. M., 18 Kresze, G., 202 Kreutzkamp, N., 98 Krivin, S. K., 129 Krivosheea, I. A., 77 Krivun, S. V., 87 Kroeker, K., 153 Krokhina, S. S., 87 Krupnov, V. K., 46 Krutskii, L. N., 56 Kubo, M., 199 KuEerovB, Z., 145 Kuchen, W., 132, 141 Kucherova, M. N., 213 Kuchitzu, K., 279 Kuczkowski, 5. A., 82,283 Kuczkowski, R. L., 278, 279 Kudryavtseva, L. A., 96 Kugel, R. L., 235 Kuhn, S. J., 210 Kuhtz, B. H., 212 Kukhar, V. P., 206, 207, 209, 214 Kukhin, V. P., 127 Kulibaba, N. K., 70 Kulik, S., 248 Kuramshin, I. Y., 140 Kurata, Y., 111 Kuriyama, K., 282 Kurz, J., 98 Kurz, K., 121 Kuwajima, I., 111 Kuzminski, B. N., 218 Kwan, T., 236, 273 Kyllingstad, V. L., 15 Kyogoku, Y., 264 Labarre, J.-F.,51, 224,277 Labarre, M. C., 282 L’Abbe, G., 185 Lacey, J. C., jun., 151 Lachmann, B., 160 Laemmerhir, K., 98 Laffler, T., 152 Lake, A. W., 182 Lam, C. W. K., 162 Lambert, J. B., 256 Lambeth, D. O., 167 Lamotte, A., 291 Lampin, J.-P., 201 Landor, P. D., 202 Landor, S. R., 202 Lane, M. D., 164 Lang, H. J., 178 Lapin, A. A., 7 Lappert, M. F., 60 Lardy, H. A,, 167 Larkin, J., 65 Larsen, B., 174 Larson, A. C., 153 Larsson, P. O., 162 Lassmann, G., 273 Lau, P. T., 1 Laurenco, C., 43 Laurent, J. P., 266 Lavielle, G., 8

Author Index

299

Lazareva, M. V., 132 Lazukina, L. A., 206 Leanza, W. J., 166 Le Corre, M., 190 Leder, P., 157 Lednicer, D., 188 Lee, I. Y., 274 Lee, J., 244 Lee, P. L., 52, 279 Lee, W. W., 147 Lehn, 5. M., 263 Leibovici, C., 224 Leissring, E., 7, 78 Leloir, L. F., 159 Lentz, A., 52, 277 Lequan, R. M., 256, 68 Lesser, J. H., 126 Le Strat, G., 127 Letcher, J. H., 251 Letsinger, R. L., 156 Letters, R., 169 Leva, M. A.. 221 Levas, E., 182 Levin, Y. A., 238, 273 Levy, J. B., 24, 59, 73 Lewars, E. G., 15, 241 Leyshon, L. J., 103, 241 Lezius. A. G.. 156 Liaaen-Jensen, S., 195 Liang, C. R., 165 Licht, E., 227, 228 Liedhegener, A., 84, 138 Lieske, C. N., 140, 173 Lightener, D. A., 183 Lim. P. K. K.. 48. 248 Lin,’Y., 173 Lincoln, S. F., 258 Lindner, C., 9 Lindner, E., 13, 78 Liober. B. G . . 141 Lipatova, 1, P., 276 Lipsky, S. R., 250 Lisovskii, I. P., 292 Listowsky, I., 168 Litoshenko, N. A., 213 Litovchenko, N. R., 208 Littauer, U. Z., 156 Littlewood, P. S., 246 Litvinenko. L. M., 127 Llinas, J., 88 Lloyd, D., 11, 188 Lloyd, D. R., 51, 281 Llovd. G. J.. 123 Lobanov, D: I., 291 Locksley, H. D., 183 Loewengart, G. V., 35, I

105

,

Loginova, E. I., 258, 265, 266 Logothetis, R. S., 180 Lohrmann, R., 147 Lohs, K., 273 Longmuir, G. H., 224 Looker, B. E., 246 Lopez, L., 48, 104 Lord, E., 188 Losi, S. A., 258 Lowe, C. R., 162 Lowe, M., 148 Luber, J., 49, 111, 274

Lucken, E. A. C., 272 Luckenbach, R., 15, 18 Luderer, T. K. J., 49, 240 Lugovkin, B. P., 92 Lumbroso, H., 286, 287 Lustig, M., 205 Lutsenko, I. F., 90, 99 Lynch, D. M., 79 Lyons, A. R., 238, 239, 272, 273 Lythgoe, B., 246 Lyznicki, E. P., 126 McCarry, B. E., 194 McColeman, C., 13, 245 McConnell, H. M., 171 McEwen, G. K., 109, 141, 267

McEwen, W. E., 15 McFarlane, H. C. E., 264 McFarlane. W.. 264 Machin, A: F.,’292 MacKay, W. D., 195 McKennon, D. W., 205 Mackey, J. K., 156 McKinley, S. V., 176, 180 McMurray, T. B. H., 57 McNeilly, S. T., 52, 77, 84, 104 Macomber. R. S.. 111 M cPhail, A. T., 282 M aeba, I., 190 M agerlein, H., 183 M arkl, G., 24 M aichuk, D. T., 151 M aier, J. P., 281 M aier, L., 78, 89, 92, 142 M‘aikova, A. I., 87 M aitra, U. S., 159 M ‘ajewski, P., 132 M[ajewski, P. J., 89 Mjajoral, J. P., 141, 270 M .akitie, O., 142 M ;alakhova, I. G., 291 M[alevannaya, R. A., 89 M[alherbe, J. S., 15, 189, 254 Mammino, J., 225 Mamonov, V. I., 90 Mancuso, A., 112 Mandel, N., 137 Mankowski-Faveli, R., 253 Mann, B. E., 252,258,266, 268 Manscher, O., 256 Manson, W., 172 Mareev, Yu, M., 90 Maria, P. C., 142 Marjoral, J. P., 142 Markl, G 269 Markovskh, L. N., 275 Marquarding, D., 29, 259 Marr, P. W., 182 Marschner, F., 23, 218, 252 Marshall, G. E., 284 Marsi, K. L., 18, 31, 79, 80, 245, 260 Marsmann, H., 267 Martin, M., 138

Martin, R. H., 196 Martynyuk, A. P., 209 Maryanoff, B. E., 113 Mashoshina, S. N., 90 Maslennikov, V. P., 126 Mastalerz, P., 139 Masters, C., 258 Mastryukova, T. A., 17, 23, 132, 141, 275, 291 Matheson, I. B. C., 244 Matheson, N. K., 160 Mathey, F., 33, 201, 253, 286. Mathiaparanam P., 41 Mathis F 109’270 Mathis: R:: 277 Matrosov, E. I., 23, 103, 218, 275, 287 Matschiner, H., 3 Matsumura, C., 279 Matysiak, Z., 292 Maumy, M., 82 Maxwell, E. S., 159 Mazepa, I. K., 68 Mazhar-ul-Haque, 35, 268 Mebazaa, M. H., 19 Medved, T. Ya., 275 Medvedeva, M. D., 114 Meister, A., 173 Mellor, M. T. J., 19, 33, 251, Melnikov, L. L., 133 Mel’nikov, N. N., 267 Merz, A., 24, 269 Meunier, J. C., 233 Meyer, G., 183 Meyers, A. I., 195 Mhala, M., 121 Michalski, J., 89, 113, 128, 132, 141, 271 Michel, R., 176 Mift’akhova, A. Kh., 275 Mikhailova, 0. B., 133 Mikhailvuchenko. N. K.. 209 Mikolajczyk, J., 113 Mikolajczyk, M., 141, 264 Miller, B., 104 Miller, 5. A., 52, 58, 65, 71, 76, 77, 80, 84, 94, ~~

104

Min, T.-B.T 237, 272 Minami, T., 19, 178, 180 Mingaleva, K. S., 286 Mirttinen, S., 142 Mislow, K., 13, 21, 27, 29, 71, 137,259,263 Missen, A. W., 271 Mitchell, A. R., 158 Mitchell, C. M., 46 Mitchell, E. W., 89 Mitchell, H. L., 64 Mitsch, C. C., 251 Mitsch. R. A.. 63 Mitschke, K.IH., 32, 62, 259

300 Mitsunobu, O., 12, 117 Miyata, Y., 145 Mizrakh, L. I., 90 Moddeman, W. E., 280 Moeller, T., 207, 215, 225 Moller, U., 4 Moffat, J., 93, 247 Mohanty, R. K., 291 Moll, E., 44, 98 Molotkovsky, J. G., 170 Molyavko, L. I., 103, 209 Monaghan, J. J., 285 Mondig, F., 226 Monson, R. S., 127 Montgomery, J. A., 160 Moore, D. R., 225 Moore, J., 205 Moreland, C. G., 251 Morgan, W. E., 280 Mori, Y., 185 Morimoto, S., 168 Morioka, S., 119, 145, 153 Moritani, I., 182 Morkovin. N. V.. 254 Morozova, I. D.,*273 Morris, C. R., 292 Morris, D. G., 204, 235, 283 Mortell, T. R., 201 Mosbach, K., 148, 162 Mosbo, J. A., 267 Moskova, 0. F., 129 Moskva, N. A., 77, 87 Moskva, V. V., 69,87,132, 269 Mostyn, R. A., 280 Motherwell, W. D. S., 7, 153 Mousseron-Canet, M., 195 Mu, P. T. K., 162 Muller, D. G., 192 Muter, B., 183 Muetterties, E. L., 29, 64, 259 Mukaiyama, T., 117, 155, 246 Mukasa, S., 202 Mukhacheva, 0. A., 84 Mukhametov, F. S., 57 Mukhametzyanova,. E. Kh., 61 Muller, A., 142 Mundrv. K. W.. 158 Munoi‘A., 38; 43, 114, 371

L.11

Munsch, B., 263 Murakami, Y., 121, 122 Muramova, A. A., 140 Murano. A.. 292 Murata,‘M.; 11, 241 Muratova, A. A., 114, 276 Murayama, A., 147 Murch, R. M., 233 Mureyama, K., 143 Murray, M., 37, 216, 261 Murray; R. -K.,-137 . Mushika, Y., 170 Musina,+A. A., 138, 276 Muslinkin, A. A., 67

Author Index Mutalapova, R. I., 258 Mutterer, F., 120, 236 Myers, T. C., 166, 251 Naan, M. P., 6, 188, 241 Nagase, M., 292 Nagyvary, J., 151 Nakajima, A., 274 Nakamura, A., 4 Nakamura, K., 233 Nakamura, T., 292 Nakanishi, A., 112, 128, 247 Nakayama, S., 241 Nakazato, H., 157 Napier, R. P., 109 Narang, S. A., 121, 155 Nasonovskii, I. S., 287 Natsume, M., 183 Natusch, D. F. S., 271 Naumov, V. A., 285 Navech, J,, 141, 142, 270 Naylor, H. G., 229 Naylor, R. A., 134 Naylor, R. N., 172 Nazar, R. N., 152 Nazarov, Yu. V., 67 Nazvanoya, G. F., 69 Nechaev, Y. D., 131 Negrebetskii, V. V., 265, 267 Neilson, G. W., 238 Neilson, T., 154 Neimysheva, A. A., 254 Nelsestuen, G. L., 159 Nemysheva, A. A., 135 Nesmeyanov, N. A., 185 Nesterov, L. V., 88, 138, 258 Neumann, R. M., 278 Neumann, U., 183 Newman, M. S., 67 Ng, T. W., 2, 288 Nicholson, D. A., 101, 131 Niecke, E., 205, 226, 265 Nierlich, F., 61, 238 Nifant’ev, E. E., 99, 113, 115, 118, 168, 211, 263, 287 Nikaido, H., 158 Nikolaev, A. F., 225, 233 Nikolaeva, V. G., 84 Nikolenko, L., 125 Nikonorova, L. K., 265 Nikonova, L. Z., 55, 56, 1n4

Nishida, S., 182 Nishino, H., 162 Nishishita, T., 258 Ni?$waki, T., 10, 90, 93, L I 1

Nitzsche, S., 233 Nixon, J. F., 265 Nohara, A., 145 Nohira, H., 1 Nomura, H., 168 Nonhebel, D. C., 65 Norman, A. D., 2 Norton, B. G., 285

Norton, I. L., 173 Norwitz, G., 280 Nose, Y., 162 Novikova, Z. S., 90, 275 Noyce, D. S., 115, 135 Nuretdinov. I. A.. 265. 266, 272 ’ Nuretdinova, 0. N.,. 55,56, . 104 Nurtdinov, S. Kh., 52, 57. 5 8 Nussbkum, A. L., 151 Nye, M. J., 77 Nys, J,, 187 Oae, S., 112, 128, 247 O’Bryan, J. M., 162 O’Connor, T. J., 2, 288 Odenwtilder, H., 24 Oehling, H., 27, 281 Oehme, H., 3, 7, 78 Ogata, Y., 13, 31, 78, 97, 23 8 Ogawa, H., 196, 199 Ogilvie, F. B., 267 Ogilvie, K. K., 153 Ogura, K., 175 Ohlsson, R., 148, 162 Ohoshi, S., 292 Ohshiro, Y., 185 Ohtsuka, E., 119, 145, 153 Ohya-Nishiguchi, H., 274 Ojala, D., 151, 152 Okada, T., 13 Okamoto, Y., 129, 138 Okawara, R., 13 Okazaki, R., 59, 241, 289 Okram, R. K., 53 Okruszek, A., 128 Okulevich, P. O., 230 Oliver, W. L., 256 Omelanczuk, J., 141, 264 Ondracek, L., 226 O’Neill, I., 195 Onodera, M., 174 Oppenheimer, A. W., 77 Oram, R. K., 30, 33, 137, 260 Orgel, L. E., 147 Oritani, T., 195 Oro. J., 146 Orth, D., 11 Orth, H. D., 143 Ortiz de Montellano, P. R., 244 Osadchenko, I. M., 79 Osborne, M. J., 159 Oshima, S., 258 Osipov, A. P., 258 Osipova, L. F., 230 Osokin, D. Y., 272 Ossip, P. S., 135 Ostanina, L. P., 87 Ostrogovich, G., 79, 281 Oswald, A. A., 126 Otsuka, H., 282 Otsuka, S., 4 Ouchi, A., 207, 215 Ovchinnikov, V. V., 276

301

Author Index Owen, G. R., 154 Ozbirn, W. P., 282

Pollard, G., 210 Polyakov, V. A., 258 Pomazanov. V. V.. 55. 104 Pongs, O., 146 Poon, R., 157 Popilin, V. P., 219 Popjhk, G., 174 Pouolin. V. P.. 233 Popovych, 0.,’291 Porter, L. J., 271 Portnoy, N. A., 82, 283 Posternak, T., 152 Potapov, A. M., 54 Potapov, V. K., 153 Poulter, C. D., 174 Powell. R. L.., 6., 32. 49. 24 1,‘255 Prabha, S., 121 Preer, J. R., 279 Prmtrazhensjkaya, N. N., ~~

Paddock, N. L., 223, 232, 23 5

Padilla, A. G., 139, 271 Painter, A. A., 167 Pan, C. S. J., 195 Panda, C. A., 248 Pantzer, R., 52 Parmeggiani, A., 151 Parodi, A. J., 159 Patel, H. A., 2, 288 Patel, N. K., 76 Patel, R. N., 174 Paterson, M. C., 173 PatoEka, J., 173 Paul, J. W., 235 Paulsen, H., 199 Pavlenko, V. A., 289 Peake, S. C., 30, 31, 63, 64, 258, 261 Pechet, M. M., 120, 236 Peguy, A., 258 Peiffer, G., 42, 88, 96 Pelavin, M., 280 Penev, P., 187 Pen’kovskii, V. V., 218, -Ai1n7

Pennington, S. N., 292 Perahia, D., 153 Perekalin, V. V., 132, 275 Peretz. J.. 136 Perkins, P. G., 224, 277 Perry, R. W., 284 Peterson, W. R., 210 Petrov, A. A., 16, 37, 42, 60, 74, 93, 96, 131, 254, 286, 288, 289 Petrov, E. S., 29, 73 Petrov, G., 141, 199 Petrova, M. V., 96 Petrovskii, P. V., 23, 141 Pfeuffer, T., 160, 161 Pfohl, S., 29, 259 Pfuller, H., 195 Phillips, L., 52, 252 Phillips, W. G., 107 Pickel, H. H., 216, 217 Piers, E., 195 Pietrusiewicz, M., 132 Pigenet, C., 287 Pilgram, K., 210 Pilot, J. F., 29, 35, 43, 259, 268, 270 Pinchuk, A. M., 127, 209, 275 Pinkerton, A. A., 275 Piskala, A., 177 Pitina, M. R., 227 Plakhanov, V. G., 3, 290 Plekhov, V. P., 276 Ploger, W., 92, 130, 131 Plotnikov, V. F., 73, 288 Pohl, H. H., 26 Pokrovskii, E. I., 101, 277 Polakis, S. E., 164 Pollard, D. R., 235

I

~

1L.J

Priess, H., 158 Prince, R. D., 183 Proctor, W. G., 280 Prokof’ev, M. A., 153 Prons, V. N., 219 Protsenko, L. D., 214, 280 Prout, C. K., 284 Pudovik, A. N., 7, 37, 56, 60, 76, 77, 82, 90, 99, 114, 135, 138, 140, 269, 275, 276, 286, 287 Pudovik, M. A., 276, 286 Puiseux-Dao, S., 280 Pujol, R., 270 Pullman, B., 153 Purdela, D., 252 Pusalkina, A. M., 87 Quick, J. E., 287 Quillinan, A. J., 183 Quin, L. D., 183,253, 256, 282 Radda, G. K., 171, 271 Radler, R., 225 Radscheit, K., 202 Raevskaya, 0. E., 82, 269, 275 Raevskii, 0. A,, 39, 276 Raftery, M. A., 256 Raylin, L. I., 254 Raigorodskii, I. M., 230, 233 Rainer, W., 233 Rajagopalan, P., 187 Rakov, A. P., 275 Rakshys, J. W., jun., 176, 180 Ramel, A., 151 Ramirez, F., 29, 35, 43, 105, 259, 268, 270, 283 Rammler, D. H., 149 Rane, D. F., 57 Ranganathan, S., 248 Rankin, D. W. H., 285 Rao, V. V. K., 142 Raphael, A., 126 Rapoport, H., 194 Rast, H., 258

Rast, M., 74 Rath, U., 156 Ratner, M. A., 51 Ratovskii, G. V., 75 Ratts, K. W., 107 Rauk, A., 29,259 Raulet, C., 182 Rausch, H., 24, 269 Rawlings, H. L., 233 Raymond, K. N., 283 Razumov, A. I., 54 69 77, 84, 87, 132, 141,’266 Razumova, N. A., 37, 41, 42, 46, 60, 74, 96, 286, 288 Razvodovskaya, L. V., 133 Readio, P. D., 10, 77 Redmore, D., 241 Rees, R. G., 88 Reese, C. B., 118, 145, 154 Regitz, M., 84, 138, 269 Reich, E., 152, 156 Reichel, L., 10, 108 Reiss, E., 3 Reiss, J. G., 69 Renz, M., 147 Reuben, J., 171 Reutov 0. A 185 Revel. b..295 Reverman, L. F., 144 Reza, M. J., 169 Rice, V. T., 102 Richards, J. B., 159 Rjchards, R. E., 171, 2 1 Richardson C. C 157 Richtaski, k.. 139’ Rigby, C.*W.; 188 Rilling, H. C., 174 Rjtchie, E., 178 Rizpolozhenskii, N. I., 54, 57, 135 Robberson, D. L., 158 Robert, D. U., 69 Robert, J. B., 271, 278 Roberts, B. P., 236, 272, 273 Roberts, J. D., 267 Robins, R. K., 143, 147 Robinson, W. H., 174 Robison G. A 143 Rockstr&h, C.1’3 Rodnyanskaya E. R 49 Roesky, H. W?., 205;’206, 212, 213, 225, 265 Rogers, P. E., 237 Rohlk, K., 279 Romanov, G. V., 7 Ronen, H., 13 Roop, B. L., 292 Roop, W. E., 292 Rose, G., 290 Rose, I. A., 163 Rosenberg, H., 165 Rosenberg, M., 158 Rosenthal, A. F., 170 Ross, F. K., 283 ROSS, S. E., 225 Rossi, G., 292 Rothius, R., 49, 240 Roundhill, D. M., 77

302 Rowe, M. J., 156 Roy, S., 151 Roychoudhury, R., 157 Rozanski, L., 287 Rubasheva, L. M., 275 Rubashevskaya, V., 17,291 Rudavskii, V. P., 207, 21 3 Rudolph, R. W., 253, 266, 278 Ruell, T., 127 Runge, W., 202 Ruschig, H., 202 Rusek, P. E., 10 Rusiecki, W., 280 RUSS,C. R., 71 Russell, J. W., jun., 183 Ruth, E., 202 Rutherford, J. S., 284 Ryan, E., 161 Ryl’tsev, E. V., 275 Sabherwal, I. H., 71 Sabin, J. R., 51 Saffhill, R., 154 Safin, I. A., 272 Saikachi, H., 196, 199 Saito, H., 224, 230, 233 Saito, T., 93, 271 Sakan, T., 194 Sakodynskaya, T. P., 211 Saksena, A. K., 246 Sakurai, H., 129, 138 Salakhutdinov, R. A., 52, 57, 87, 141 Salikhov, S. G., 258 Salomon, Y., 148 Salser, W., 157 Sam, T. W., 245 Samarai, L. I., 215 Samitov, Y. Y., 138 Sammes. P. G.. 246 Sampson, E. J.; 125 Sanchez, M., 44 Sanders, J. K. M., 257 Sandmann, H., 31, 253 Sanger, F., 157 Sanno, Y., 145 Sano, T., 12 Saran, A., 153 Sarantakis, D., 192 Sargent, M. V., 198, 199 Sasaki, T., 11, 185, 241 Sasse, K., 58 Satchell, D. P. N., 163 SatgC, J., 39, 72 Sato, K., 196 Sato, M., 236, 273 Sato, S.-J., 111 Saunders, D. G., 103, 241 Saunders, V. R., 51, 277, 28 1 Saussez, R., 27, 239 Savchenko, L. Ya., 94 Savelova. V. A.. 127 Savelpevh, N. I.’, 99 Savicheva, G. A., 141 Savignac, D., 120 Savignac, P., 49

Author Index Saxon, G., 158 Scarlata, G., 287 Schadenberg, H., 190 Schafer, H., 71 Schafer, W., 26, 27, 281 Schaffer, O., 27, 244 Schattka, K., 145 Scheider, D. F., 15 Scheinmann, F., 183 Scheit, K. H., 144 Scherer, A., 125 Scherer, H., 269 Schiemenz, G. P., 15, 74, 258, 277, 279, 280, 290 Schiller, H. W., 253, 278 Schindler, N., 92, 130 Schliebs, R., 120 Schlosser, M., 177, 180 Schmidbaur, H., 32. 62, 176, 216, 217, 258, 259, 248 Schmidpeter, A., 49, 89, 91, 111, 203, 220, 221, 223, 274 Schmidt, U., 132, 241 Schmidt-Samoa, E., 98 Schmutzler, R., 30, 31, 37, 39, 63, 64, 69, 70, 204, 216,. 217, 258, 261 Schneider, D. F., 189, 254 Schubert, G., 136 Schuessler, D., 102 Schultz, C. W., 266 Schulz, D. N., 15 Schuman, D. A., 143 Schwartz, J. H., 172 Schweig, A., 27, 281 Schweiger, J. R., 31, 63, 27 1 Schwkzer, E. E., 19, 21, 23, 42, 178, 180, 189, 191. 254. 269 Schwendeman, R. H., 52, 279 Schwyzer, R., 148 Scott, M., 148, 162 Seel, F., 53, 62, 85, 110, 253. 268. 290 Seeliger, A’., 10, 246 Selinger, Z., 148 Selve, C., 18, 246 Semashko, V. N., 285 Semenii, V. Ya., 207, 214 Semenii, Y. Y., 127 Senges, S., 282 Senkler, G. H., 71 Sepulveda, L., 121 Serafini, A., 51, 277 Sergeev, G. B., 258 Sergeeva, V. P., 126 Sergeyev, N. M., 255 Seto, S., 175 Seyferth, D., 84 Shabana, R., 92 Shabarova, Z. A., 153 Shagidullin, R. R., 276 Shahak, I., 136 Shakirova, M. A., 275 Shapoval, G. S., 219 Sharp, D. W. A., 64

Shatenshtein, A. I., 73, 29 1 Shaver, A.. 220 Shaw, B. L., 258, 268 Shaw, N., 171 Shaw, R. A., 231,284, 290 Shchelkina, E. P., 187 Shealy, Y. F., 160 Shen. T. Y.. 158 Sheleton, R:, 157 Shermergorn, I. M., 61 Shevchenko, V. I., 70, 127, 208, 209 Shevchuk, M. I., 10, 177, 187, 190 Shibata, T., 279 Shikanian, K., 153 Shila, S. I., 68 Shilov, I. V., 99 Shimada, Y., 109, 119 Shimomura, M., 168 Shipov, A. E., 141 Shirankov, D. F., 213 Shmukler, H. W., 292 Shokol, V. A., 103, 207, 209, 210 Shook, H. E., jun., 183 Shostenko, A. G., 61 Shpak, S. T., 10 Shtepanek, A. S., 217 Shuikin, N. I., 56, 69 Shukla, R., 98 Shurukhin, B. B., 37, 96 Shushunov, V. A 126 Shvetsov-Shilovsl&. N. I.. 227, 290 Shvetsov-Shilovskii, Y., 267

Sidky, M. M., 92 Siewers, 1. J., 168 Silman, I., 143 Sim, G. A., 182 Simalty, M., 19, 185 Simon, L. N., 143, 147 Simonnin, M. P., 256, 261, 268 Simpson, P., 107 Sinanoglu, O., 281 Singer, M. F., 156 Singer, M. I. C., 11, 188 Singh, H., 282 Sisler, I-I. H., 18 Sklarz, B., 247 Skoda, J., 145 Skul’skaya, N. Ya., 214, 280 Skvortsov, N. K., 254 Skylarskii, L. S., 118 Slade, R. M., 258 Slater, E. C., 274 Sletzinger, M., 166 Smakhtin, L. A., 292 Smets, G., 185 Smith, B. C., 284 Smith. C. P.. 29. 35. 259. 268’ Smith, D. J. H., 133, 179 Smith, D. J. M., 53, 137 Smith. J. E.. 52. 279 Smith; M. A., 156 I

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303

Author Index Smrt, J.. J., 154 Smyrl, T. G., 136 Smythe, R. J., 13, 245 Snider, T. E., 18, 270 Snyder, C. D., 194 Snvder. E. I.. 8 Snider; S. L.’, 172 Sokal‘skaya, L. I., 101 Sokal’skii, M. A., 52, 64 Sokolov, M. P., 141 Sokurenko, A. M., 118 Soliman, F. M., 92 Solodushenkov, S. N., 206 Solomonovici, A., 200 Sommer, K., 252 Sommer, R. G., 144 Sondheimer, F., 198, 199 Sorm, F., 143 Sorokina, T. D., 90 Soulen, R. L., 182 Southern, E. M., 158 Sowerby, D. B., 226, 227 Spector, L. B., 172 Spencer, N., 163 Spivak, L. L., 291 Sprecher, M., 163 Sprinson, D. B., 163 Spruegel, W., 187 Stabrovskaya, L. A., 82, 269 Stache, U., 202 Stackhouse, J., 263 Stadelmann, W., 70, 204, 217 Stadnichuk, M. D., 183 Stade, W., 25 Stahler, H., 268 Stainbank, R. E., 258, 268 Stanko, J. A., 235, 284 Starkovsky, N. A., 154 Stary, H., 221 Stead, A., 171 Stec, W., 128, 207 Stec, W. J., 255, 265, 280 Steele, J. C. H., 282 Stegmann, H. B., 212, 237 Stein, M. T., 235, 284 Steinberg, G. M., 140 Steinmetzer, H.-C., 190 Stelzer, O., 70, 204, 217 Stepanov, B. I., 224, 231, 279 Stephani, R. A., 173 Sternbach, H., 144 Stevenson, G., 94 Stevenson, G. M., 76 Stevenson. R., 65 Steward, J. HI, 292 Stille, J. K., 85 Stockdale, B. R., 65 Stocks. R. C.. 256 Stocker, F., 212, 237 Stoll, H., 52 Stoll, K., 221 Stone, F. G. A., 46 Stone, K. J., 175 Straus, D. B., 143 Streeter, D. G., 156 Strizhov, N. K., 90 Stroh, E. G., 235

Strominger, J. L., 161, 175 Struck, R. F., 160 Strukov, 0. G., 64 Strzelecka, H., 178 Stubbe, J. A., 162 Stuhler, H., 32, 176, 258 Stukalo, E. A., 70 Sturtz, G., 126 Suard, M., 280 Sudakova, T. M., 76, 90 Suerbaev, Kh. A., 23 Sugaya, H., 183 Suggs, J. L., 81, 130, 289 Sukhorukova, N. A,, 75 Suleimanova, M. G., 85 Sultan, M. K., 247 Sultanova, D. B., 87 Sumskaya, E. B., 23, 187 Sunamoto, J., 121, 122 Sundaralingam, M., 284 Suoboda, P., 2 Susz, B. P., 258 Sutcliffe, L. H., 252 Sutherland, E. W., 143 Sutherland, J. K., 245 Suzuki, H., 233 Suzuki, Y., 185 Svergun, V. I., 90, 279 Swan, J. M., 16 Swank, D. D., 43, 270 Swartz, W. E., jun., 254 Swiatek, K. R., 147 Symes, K. C., 77 Symmes, C., 24, 59, 73 Symons, M. C. R., 51,238, 239, 272, 273 Szab6, L.! 168 Szutowski, M., 280 Tachikawa, R., 195 Taft, A., 32 Tagaki, W., 122 Tait. B. S.. 48. 248 Tajima, K:, 155 Takahashi, M., 183 Takahashi, Y.,281 Takaku, H., 109, 119 Takanisji, T., 144 Takeuchi, Y., 10, 246 Takizawa, T., 6, 189 Tamura, C., 47, 254 Tan, H.. 141 Tan; S. A., 292 Tana, I., 122 Tanaka, H., 292 Tang, R., 27, 263 Tani, K.. 4 Tanner, W., 159 Tarasevich, A. S., 218 Tarasova, R. I., 99 Tasaka, K., 35, 105 Tate, M. E., 292 Tatsuta, K.,175 Taunton-Rigby, A., 154 Taylor, M. V., 246 Taylor, N. F., 169 Taylor, R. C., 257 Taylor, W. C., 178 Tazawa, I., 156 Tchanyi, B., 265

rebby, J. C., 6 reraji, T., 182 Terent’eva, S. A., 286 rereshchenko, G. F., 254 Tesoro, G. C., 225 Tesser, G. I., 148 Teste, J., 128 Tewari, R. S., 98 Texier, F., 185 Thakur, C. T., 284 Thaller, V., 195 Thamm, H., 226 Thanwalla, C. B., 140 Thedford, R., 143 Thiem, J., 199 Thompson, A. R., 102 Thomson, C., 28, 74, 239, 273 Thorstenson, P. C., 97, 244 Tidwell, T. T., 125, 126 Tikhonina, N. A., 219 Timmler, H., 98, 121 Timofeeva, T. N., 256 Timokhin, B. V., 1, 75, 76 Titov, S. S., 142 Tkachenko, E. N., 217 Tokunaga, H., 183 Tolochko, A. F., 177 Tomaszewski, M., 149 Tomilov, A. P., 79 Toropova, V. F., 275 Torrence, P. F., 143, 155 Toscano, V. G., 84 Tossidis, I., 142 Towns, R. L. R., 283 Trachtman, M., 280 Tran’kova, N. A., 1, 76 Traynard, J. C., 88 Trefonas, L. M., 73, 283 Treon, K., 74, 258 Tribout, J., 196 Trigalo, F., 168 Trippett, S., 30, 33, 53, 74, 133, 137, 179, 258, 260 Tronchet, J. M. J., 199 Trotter, J., 235 Troy-Lamire, D., 28 1 Trutneva, E. K., 238 Tsay, F. D., 279 Tsentovskii, V. M., 287 Tsivunin. V. S..I 52., 56.I 57, 58‘ Ts’o, P. 0. P., 146,147,271 Tsolis, E. A., 29, 35, 105, 259 Tsou, K. C., 153 Tsuchiva. T.. 175 Tsuda,-E:, 182 Tsuda, Y., 173 Tsuji, H., 258 Tsujimoto, N., 128, 247 Tsvetkov, E. N., 73, 89, 29 1 Tsyba, V. T., 216 Tu, S. I., 167 Tucker, P. A., 284 Tudrii. G. A.. 42. 96 Tukhar, A. A’., 210 Tulloch, C. D., 196

304 Tunggal, B. D., 269 Turchinsky, M. F., 149 Turnblom, E. W., 30, 46 Turner, D. M., 169 Turner, D. W., 281 TurDin. R.. 281 Tusek, ‘Lj.,.92 Tusl, J., 280 Twitchell, D., 32 Tzschach, A., 3 Ubasawa, M., 145 Uchida, M., 111 Uchtman, V. A., 284 Udy, P. B., 205 Uesugi, S., 282 Ugi, I., 29, 259 Ulrich, S. E., 72, 266, 268 Umezawa, S., 175 Underwood, W. G. E., 246 Urushibara, T., 174 Urzhuntseva, E. K., 291 Ustynyuk, Y. A., 255 Utvary, K., 214, 216 Uzlova, L. A., 199 Vafina, A. A., 273 Vagelos, P. R., 171 Vaisberg, M. S., 141 Valitova, L. A., 87 van Boom, J. H., 154 Van der Kelen, G. P., 287 Vandi, A., 207, 215 Vandoorne, W., 284 Van Dormael, A., 187 Van-Dyke, C. H., 69 Van Etten, R. L., 172 Van Gelder, B. F., 274 Van Leemput, R., 233 van Tamelen, E. E., 194 Van Wazer, J. R., 64, 187, 214, 220, 251, 255, 265, 278, 279, 280 Vargas, L., 170 Varvoglis, A. G., 87, 130 Vasil’ev, A. F., 267 Vasyanima, M. A., 138 Vaughan, M. H., jun., 157 Vaughn, H., 101, 131 Vaziyanova, P. F., 129 Vedejs, E., 8 Veillard, A., 51, 277 Velleman, K. D., 53, 62, 85, 110, 253, 268, 290 Venanzi, L. M., 2 Venezky, D. L., 287 Vere Hodge, R. A., 195 Verhelst, A., 61, 238 Verkade, J. G., 109, 141, 267 Versino, B., 292 Vesper, J., 3, 253 Vikane, T., 89, 141 Vilkas, M., 118, 145 Vilkov, L. V., 282 Villieras, J., 8 Vilsmaier, E., 187 Vincent, A. T., 283 Vinogradov, B. A., 289

Author Index Vinogradova, V. S., 42, 90, 96 Vinot, G., 51, 277 Virgilio, J. A., 115, 135 Viterbo, R., 141 Vizel, A. O., 46, 57, 275 Vizgert, R. V., 138 Vnek, J., 163 Vogel, E., 198 Vogt, w., 110 Voigt, D., 281, 282 Volashin, M. P., 138 Vollhardt, K. P. C., 196, 198, 199 Voloboeva, L. V., 69 Volynskaya, E. M., 187 von Philipsborn, W., 264 Vornberger, W., 176, 268 Vouros, P., 290 Voziyanova, 0. F., 87 Voznesenskaya, A. K., 42, 96 Wachob, G. D., 183 Wada, M., 12 Waddington, T. C., 251 Wadsoe, I., 291 Wagner, A. F., 158 Wagner, A. J., 224, 235, 284

Wagner, E. L., 278 Wahl, G. H., 257 Waite. N. E.. 6 Wakagawa, h., 196 Wakeford, D. H., 118, 119 Waki, H., 292 Wakselman, M., 118, 145 Walker, B. J., 74, 177, 258, 262 Waller. R. L.. 86. 137.243. 290 Walsh, E. J., 228, 231 Walters, D. B., 257 Wampler, D. L., 153 Wander, J. D., 82, 283 Wanek. W.. 226 Wang, J. H:, 167 Wang, T., 172 Ward, D. C., 156 Ward, T. M., 257 Warren, S., 82, 83, 153 Warren, W. A., 165 Washburne, S. S., 210 Wasserstein, P., 163 Waters, J. A., 155 Watson, D. G., 153 Watts, G. B., 236, 274 Weatherall, I., 254 Weatherburn, D. C., 291 Webb, S. B., 61, 129, 238, 29 1 Weber, J., 265 Wedler, F. C., 174 Weeks, J. E., 88 Weetall, H. H., 161 Wehman, A. T., 178 Wehrli, F. W., 256 Weibel, M. K., 161 Weichmann, H., 4 Weidlein, J., 32, 62, 259 I

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I

,

Weigert, F. J., 267 Weingand, A., 220 Weinstein. B.. 192 Weisheit, -W.,’265 Weiss, D., 10 Werstiuk, E. S., 154 Westheimer, F. H., 27, 131 Wetzel. R. B.. 74 Whalley, W. B 192 Wheatley, P. J.Y283 White, D. W., 32, 34, 49, 113, 141, 255, 260, 263 White, G. F., !63 White, W. E., jun., 151 Whitehead, M. A., 219, 224, 272 Whitesides, G. M., 64 Wieland, T., 119, 166, 246 Wiesner, K., 195 Wjesner, K. J., 195 Wightman, R. H., 121, 155 Wilchek, M., 148 Wilkerson, C., 245 Wilkes, J. S., 156 Wilkinson, G., 77 Williams, A., 134, 172 Williams, B. C., 76, 94 Willjams, D. H., 257 Williams, F., 239 Willjams, J. C., 82, 283 W/ll!ams, V. P., 174 Willis, B. J., 246 Willson, M., 109 Wilson, D. B., 159 Wilson. D. P.. 144 Wilson; I. B., ’172 Wilt, E. M., 157 Wingfield, J. N., 235 Witkop, B., 143, 155 Wltt, E. R., 41, 101, 264 Wittia. G.. 1. 15 Wofslkjr, S: C., 278 Wolf, R., 38, 43, 44, 114, 271, 282 Wolfsberger, W., 216, 217 Wollmann, K., 131 Wong, J. T., 152 Wong, S. C. K., 203 Wong, S. M., 174 Wood, H. C. S., 65 Woodcock, R., 125 Woods, A. E., 162 Woods, M., 284, 290 Woplin, J. R., 37, 216, 261 Worms, K. H., 131 Wray, V., 52, 252 Wreland, T., 10 Wright, J. A., 169 Wright, S. H. B., 16 Wuest, H., 15, 182 Wynberg, H., 190, 196 Yagi, K., 174 Yakovleva, T. V., 46 Yakshin, V. V., 101 Yakutina, 0. A., 1, 76 Yamada, K., 22, 245 Yamada, S., 10, 246 Yamashita, K., 195

305

Author Index Yamashita, M., 13, 31, 78, 97,238 Yamazaki, A., 153 Yamazaki. H.. 152 Yamazaki; N.; 114 Yanagita, M., 236, 273 Yankelevich, A. Z., 265 Yarkova, E. G., 114, 140, 276 Yato, T., 188 Yee. K. C.. 74. 141. 257.

Yoneda; S.,’187, 188 Yong, K. S., 82, 283 Yoshida, H., 156 Yoshida, K., 282 Yoshida, N., 282 Yoshida, Z., 187, 188 Yoshifuji, M., 59, 241, 289 Yoshikawa, M., 144

Yoshina, S., 190 Yoshioka, T., 185 Young, D. E., 63, 72 Young, I. M., 84, 104 Young, V. A., 125 Yount, R. G., 151, 152 Yuki, R., 156 Yurchenko, R. I., 210 Yurzhenko, T. I., 213 Yvernault, T., 240 Zagnibida, D. M., 207, 213 Zagorets, P. A., 61 Zaripov, N.-M., 285 Zarkadas, A., 2, 71 Zarytova, V. F., 153 Zasorina, V. A., 217 Zavalishina, A. I., 115 Zavlin, P. M., 49 Zawadzki, S., 120 Zbiral, E., 22, 189 Zeiss, W., 89, 91, 203, 223 Zeleneva, T. P., 224 Zemlyanskii, N. I., 128 Zenin, S. V., 258 Zentil, M., 282 Zhdanov, Yu. A., 199

Zhivukhin, S. M., 219, 233 Zhmurova, I. N., 209,210, 219 Zhukov, V. P., 56 Zhuraleva, L. P., 85 Ziehn, K. D., 9, 10, 203, 210,211 Zimin, M. G., 77, 275,287 Zimmer, G., 125 Zimmermann, R., 176, 177 Zinkovskii, A. F., 94 Zmeltukhin, V. F., 67 Zoer, H., 235 Zon, G., 27, 137, 263 Zoroastrova, V. M., 42,96 Zoroatskaya, E. I., 273 Zubtsova, L. I., 46, 60, 74, 96, 288 Zuckermann, J. J., 72, 266, 268 Zurflueh, R., 202 Zutra, A., 156 Zwierzak. A.. 113. 117. 120, 271 Zykova, T. V., 52, 57, 58, 69, 77, 87, 141, 269 Zyryanova, T. A., 233 ~~

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