Organophosphorus Chemistry

A Specialist Periodical Report

Organophosphorus Chemistry Volume 5

A Review of the Literature Published between July 1972 and June 1973

Senior Reporter

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

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

J. A. Miller, Universify of Dundee

D. J. H. Smith, University of Leicesfer J. C. Tebby, North Staffordshire Polyfechnic B. J. Walker, Queen’s University

of Belfast

0 Copyright 1974

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

ISBN : 0 85186 046 X Library of Congress Catalog Card No. 73-268317

Printed in Great Britain by Adlard & Son Ltd. Bartholomew Press, Dorking

Foreword

The pattern set in previous volumes has been continued, although increasing activity in several areas has required more selectivity on the part of Reporters. The year under review has in general been one of consolidation with few major advances. However, it did see the start of publication of the new ‘Kosolapoff’ replacing the first edition1 which has been an essential hand-book for all organophosphorus chemists since it appeared in 1950. Now edited jointly by Gennady Kosolapoff and Ludwig Maier the new edition,2 so far in four volumes, is a worthy successor to its one-volume predecessor. October 1973 1

a

S. Trippett

G . M. Kosolapoff, ‘OrganophosphorusCompounds’, Wiley, New York, 1950. ‘Organic Phosphorus Compounds’, ed. G. M. Kosolapoff and L. Maier, Wiley-Interscience, New York, 1973, vol. 1 4 .

V

Contents Chapter 1 Phosphines and Phosphonium Salts By D. J. H. Smith 1 Phosphines Preparation From Halogenophosphines and Organometallic Reagent From Metallated Phosphines By Reduction Miscellaneous Reactions Nucleophilic Attack on Carbon Ac:tivated olefins Activated acetylenes Carbonyls Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous 2 Phosphonium Salts

Preparation Reactions Alkaline Hydrolysis Additions to Vinylphosphonium Salts Miscellaneous

1

1 1

1 1 4 5 7 7 7 8 9 10 12 13 15 15 18 18 21 24

3 Phosphorins Preparation Reactions

25 25 28

4 Phospholes Preparation and Reactions Physical Measurements

30 30 32

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett

34

1 Ligand Reorganization and Structure

34

2 Acyclic Systems

35

vi

Contents 3 Three-membered Ring

37

4 Four-membered Rings

37

5 Five-membered Rings Phospholans and Phospholens 1,3,2-Dioxaphospholans 1,3,2-Dioxaphospholens 1,2-0xaphospholens 1,3,2-0xazaphospholens 1,3,5-Oxazaphospholens Miscellaneous

39 39 40 42 44 44 46 47

6 Six-membered Ring

49

7 Six-co-ordinate Species

49

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller

52

1 Halogenophosphines Physical Aspects Reactions Electrophilic Attack by Phosphorus Nucleophilic Attack by Phosphorus Biphilic Reactions Miscellaneous Reactions

52 52 53 53 56 56 59

2 Halogenophosphoranes

60 60 62 63

Structure and Bonding Preparation Reactions

Chapter 4 Phosphine Oxides, Sulphides, and Sefenides By J. A. Milter

70

1 Introduction

70

2 Preparation From Secondary Phosphine Oxides or from Phosphinites

70 70

vi i

Contents By Grignard and Related Reactions By Oxidation of Phosphines By Miscellaneous Routes

3 Reactions and Properties

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

72 73 76 79

83

83

2 Phosphorous Acid and 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

83 83 83 86 98 99 101 103 105 105 109

3 Phosphonous and Phosphinous Acids and Derivatives

111

Chapter 6 Quinquevalent Phosphorus Acids By N. K. Hamer

112

1 Phosphoric Acid and Derivatives Synthetic Methods Solvolyses of Phosphoric Acid Derivatives Reactions of Phosphoric Acid Derivatives

112 112 115 121

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

127 127 130 132 138

...

Contents

Vlll

Chapter 7 Phosphates and Phosphonates of Biochemical Interest 141 By D. W. Hutchinson 1 Introduction

141

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

141 141 150 152 156

3 Coenzymes and Cofactors

157 157 158 158

Nucleoside Diphosphate Sugars Vitamin Be and Related Compounds 0ther Coenzymes 4 Naturally Occurring Phosphonates

160

5 Oxidative Phosphorylation

161

6 Sugar Phosphates

163

7 Phospholipids

164

8 Enzymology

165

9 Other Compounds of Biochemical Interest

167

Chapter 8 Ylides and Related Compounds By S. Trippett 1 Methylenephosphoranes

Preparation Reactions Halides Carbonyls Miscellaneous

170

170 170 172 172 174 179

2 Phosphoranes of Special Interest

181

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

188 188 191 192

ix

Contents

4 Selected Applications of Phosphonate Carbanions

194

5 Ylide Aspects of Iminophosphoranes

197

Chapter 9 Phosphazenes By R. Keaf

200

1 Introduction

200

2 Synthesis of Acyclic Phosphazenes From Amides and Phosphorus(v) Halides From Azides and Phosphorus(m) Compounds 0ther Methods

200 200 202 205

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

207 207 210

4 Synthesis of Cyclic Phosphazenes

213

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

217 217 219 222 223

6 Polymeric Phosphazenes

225

7 Molecular Structures of Phosphazenes Determined by X-Ray Diffraction Methods

226

Chapter 10 Photochemical, Radical, and Deoxygenation Reactions By R. S. Davidson 228 1 Photochemical Reactions

228

2 Phosphinidenes and Related Species

229

3 Radical Reactions Structure a-Cleavage Reactions B-Scission Reactions

230 23 1 232 233

Contents

X

Relative Ease of a- and &Scission Reactions Other Aspects of the Chemistry of Phosphoranyl Radicals

4 Deoxygenation Reactions Ozone and Ozonides Molecular Oxygen Hydroperoxides and Peroxides Oxaziridines and Oxadiazoles Sulphoxides Mono- and Poly-sulphides and Elemental Sulphur N-Oxides, Nitroso- and Nitro-compounds

Chapter 11 Physical Methods By J. C. Tebby

234 234 238 238 239 239 240 241 242 243 247

1 Nuclear Magnetic Resonance Spectroscopy Chemical Shifts and Shielding Effects Pho~phor~s-31 BP of PI1 compounds BP of PII1 compounds BP of P I V compounds BP of Pv compounds Isotope effects on 8p Carbon-13 Hydrogen-1 Studies of Equilibria, Reactions, and Solvent Effects Pseudorotation Restricted Rotation Inversion, Non-equivalence, and Configuration Spin-Spin Coupling JVP) and JPM) JPC) lJ(PH) J(PCnH) JPXCnH) Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies

247 247 247 248 248 250 252 253 253 254 254 256 258 259 260 261 262 263 264 266

2 Electron Spin Resonance Spectroscopy

269

3 Vibrational Spectroscopy Stereochemical Aspects Studies of Bonding

270 273 274

268

xi

Contents

4 Microwave Spectroscopy

275

5 Electronic Spectroscopy

275

6 Rotation and Refraction

278

7 Diffraction

279

8 Dipole Moments, Conductance, and Polarography

282

9 Mass Spectrometry

284

10 pKand Thennochemical Studies

287

11 Surface Properties

289

Author Index

290

Abbreviations

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

TCNE THF t .l.c.

bisazoisobutyronitrile 1,5-diazabicyclo[4,3,0]non-5-ene l,S-diazabicyclo[5,4,0]undec-Sene dicyclohexylcarbodi-imide NIV-dimethylformamide dimethyl sulphoxide gas-liquid chromatography hexamethylphosphoric triamide N-bromosuccinimide nuclear quadrupole resonance inorganic pyrophosphate tetracyanoethylene tetrahydrofuran thin-layer chromatography

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

1 Phosphines Preparation.-Many of the papers published in the year under review on the preparation of phosphines were minor variations of well proven routes. A number were concerned with making novel polyphosphines or cyclic phosphines for use as ligands. The preparation and reactions of phosphinesl and poly(tertiary phosphines) have been reviewed. From Halogenophosphines and Organometallic Reagent. Bis(dialky1aminoph0sphine)acetylenes (1) have been obtained by the reaction of acetylenedimagnesium dibromide with the appropriate chloropho~phine.~ BrMgC-CMgBr

RC-CLi

-I- (R12N)R2PCl

+

Ph,PCI

(RlaN)R2PCrCPR2(NRl,)

(I) Ra = R1,N or Me

* RC-CPFhs ‘B!oHlo (2) R = CHr= CH,H, Me, or Ph

‘B:OH, (3)

Pa14

-

+

/

pyridine

CH,(SH)s

_ _ _ f

CHI

‘s-P-s (4) 24%

The new carbaborane-containing ligands (2) have been synthesized by treatment of chlorodiphenylphosphinewith the carbaboran-1-yl-lithiums (3). Some of these phosphines are stable to atmospheric ~ x y g e n . ~ The reaction of methanedithiol with diphosphorus tetraiodide in the presence of pyridine gave the new phosphorus-sulphur heterocycle (4).6 From Metallated Phosphines. Sodium diphenylphosphide, prepared by the L. Maier, in ‘Organic Phosphorus Compounds’, ed. G. M. Kosolapoff and L. Maier, Wiley-Interscience, 1972, Vol. 1, p. 1. R. B. King, Accounts Chem. Res., 1972, 5, 177. W. Kuchen and K. Koch, 2. anorg. Chem., 1972,394,74. L. I. Zakharkin, M. N. Zhubekova, and A. V. Kazantseu, J. Gen. Chem., (U.S.S.R.), 1972,42, 1013. M. Baudler, K. Glinka, U. Kelsch, H. Sandmann, and W. Heller, Phosphorus, 1972, 2, 161.

1

2

Organophosphorus Chemistry

addition of sodium to a dioxan solution of ethyl diphenylphosphinite, when added to 1,2-dichloroethane gave a high yield of the diphosphine (5).6 The chiral diphosphine (6) containing a dioxolan ring, which has been used as a ligand in asymmetric catalysts, has been synthesized from the corresponding tosylate by reaction with sodium diphenylph~sphide.~ Ph2PNa

ClCHgCH &1

PhPCH2CH2PPh2 (5) 94%

H

H

V

C

N

(7) [Me,N=CHCI]+ Cl- 3. R2PLi + (R2P),CHNMeB (8) R = Me, Et, or Ph (9) Me,NCH(OMe),

+ R2PH

(10)

(2-Cyanophenyl) diphenylphosphine (7) has been prepared by the dropwise addition of 2-chlorobenzonitrile to a stirred, refluxing, solution of lithium diphenylphosphide.8 Aminophosphinomethanes (8) are obtained from the reaction of the corresponding phosphide with the salts (9) or the dimethyl acetals (10). These phosphines can also be made directly from (10) and the secondary pho~phine.~ Dipotassium triphenylcyclotriphosphanecan be prepared by metallation of pentaphenylcyclopentaphosphane (1 1) with a stoicheiometric amount of potassium in benzene.lo Reaction with iodine at - 78 "C followed by decomposition gave pure triphenylcyclotriphosphane (12), which is stable below - 20 "C but rearranges to the more stable (1 1) at higher temperatures. Mann has shownll that the dilithiotriphosphane (13), obtained by the action of lithium on (1 1) or dichlorophenylphosphine, reacts with o-bromo-

K

(PhP),

K,(PhP),

A

KB(PhP)J2

-

(PhP),

(1 1) (12) * H. Nohira, M. Taniguchi, and K. Shimamura, Jap. P. 72 47 014/1972 (Chern. A h . , 1973, 78, 84534). H. B. Kagan and T.-P. Dang, J. Amer. Chem. SOC.,1972,94, 6429. D. H. Payne and H. Frye, Inorg. Nuclear Chem. Letters, 1972, 8, 73. K. Issleib and M. Lischewski, J. Organometallic Chem., 1972, 46, 297. l o M. Baudler and M. Bock, 2. anorg. Chern., 1973, 395, 37. 1 ' F. G. Mann and A. J. H. Mercer, J. C.S. Perkin I, 1972, 1631.

Phosphines and Phosphoniunz Sults

+ PhP-P-PPh

3

+ m ” Y h

B’/PPh Li

(13)

Ph

chlorobenzene in a two-step process to give the triphosphane (14). Similarly, refluxing (11) with potassium in THF followed by addition of 1,2-dichloroethane12 gave the 1,2,3-triphosphane (15). The addition of an equimolar amount of j3-propiolactone to a benzene solution of ethylzinc diphenylphosphide gave a crystalline material, formulated as (16), which probably arises from initial acyl-oxygen bond cleavage followed by 1,4-addition of the ph0~phide.l~ 0

EtZnPPh,

+

CHa-C=O

I

CHa-0

t

II

+ EtZnOCHaCH8CPPh8

J. 0

Ph2PCHBCH=COZnEt

I

ll

f-

CH2=CHCPPhB

+ EtZnOH

PPha (16)

Acylphosphine (17) can be prepared by the reaction of diphenyl(trimethy1sily1)phosphine and oxalyl chloride. The interesting dione (18) was obtained in a similar reaction.14 Aromatic acid chlorides also react with diphenylM. Baudler, J. Vesper, and H. Sandmann, Z. Naturforsch., 1972, 27b, 1007 (Chem, Abs. 1973, 78, 16106). J. Boersma and J. G. Noltes, Rec. Trav. chim., 1973, 92, 229. H. J. Becker, D. Fenske, and E. Langer,!Chem. Ber., 1973,106, 177.

In

la

4

Organophosphorus Chemistry 2Ph2PSiMes

+

2Ph2PSiMe,

+

ClOCCOCl

O

x

c1

ArCOCl

+

o

Ph2PCOCOPPh2 (17)

+ O x o

Ph ZP

c1

PhaPSiMe3

ArCOPPh2

II

II

Ph2P-SPh

+ CH2=C=O O'hCH38'H (20)

+

CFBCOCl

+ Me3SiC1 0

0 PhS02Cl 3. 2Ph2SiMe, -+

PPh2

4- Ph2P-OH

(PhCHJ2PCOCHa . pyridine

(PhCH2)2PCOCFS

(trimethylsily1)phosphine to give acylphosphines, but benzenesulphonyl chloride gave the diphenylphosphinic ester (19).15 Acylation of dibenzylphosphine (20) can conveniently be carried out by reaction with keten or trifluoroacetyl chloride in the presence of pyridine.ls Ketens add to germyl- or silyl-phosphines to give the phosphorylated alkenoxy-germanes or -silanes (21).17 Diketen also reacts to yield (22), by isomerization of the initial adduct ; hydrolysis of (22) gave phosphorylated p-diketones. By Reduction. An improved procedure for the preparation of phenylphospiiine by the reduction of dichlorophenylphosphine with lithium aluminium hydride at - 78 "C has been reported.ls A number of polyphosphines, containing primary, secondary, or tertiary phosphorus, e.g. (23), have been prepared by the addition of a phosphine across the double bond of an unsaturated phosphorus ester, followed by reduction with lithium aluminium hydride.ls H. Kunzek, M. Braun, E. Nesener, and K. Ruhlmann, J. Organometallic Chem., 1973, 49, 149. l6 R. G. Kostyanovskii, Y . I. El'natanov, L. M. Zagurskaya, K. S. Zakharov, and A. A. Fomichev, Bull. Acad. Sci., U.S.S.R., 1973, 21, 1841. 1 7 C. Couret, J. Satge, and F. Couret, J. Organometallic Chem., 1973, 47, 67. la R. C. Taylor, R. Kolodny, and D. B. Walters, Synrh. Inorg. Mefal-org. Chem., 1973, 3, 175. R. B. King and J. C. Cloyd, 2. Naturforsch., 1972, 27b, 1432 (Chem. A h . , 1973, 78, 72 298). 16

5

Phosphines and Phosphonium Salts R'sMPEt2

R'sMPEt,

+ R*ZC=C=O

+ CH,=C-CH, I

I

0-c=o MeCCH2CPEt2

II

0

II

0

10 R1,M-O-C=CHCOpEt2 t

Me (22)

R1= Et or Me; R2= H or Ph; M = Ge or Si Phenylsilane was found to be the best reducing agent for converting the phosphorus acid or ester (24) into the secondary phosphine.aO

Miscellaneous. Silylphosphine (25) has conveniently been prepared in good yield by the reaction of silane and phosphine with a catalytic amount of iodine.21 Tris(hydroxymethy1)phosphine (26) can be produced quantitatively by passing phosphine into a solution of formaldehyde in methanola2or ~ y l e n e ~ ~ at 75-90 "C under pressure. C. N. Robinson, W. A. Pettit, A. William, T. 0. Walker, E. Shearon, and A. M. Mokashi, J. Heterocyclic Chem. 1972, 9, 735. I. H. Sabhenval and A. B. Burg, Inorg. Nuclear Chem. Letters, 1972, 8, 27. la R. F. Stockel and W. F. Herbes, Ger. Offen. 2158823 (Chem. Abs., 1973,78,43702). ** R. F. Stockel and W. F. Herbes, U.S.P. 370432$/1972 (Chem. Abs., 1973, 78,43703).

Organophosphorus Chemistry

6

PH3

+

HCHO

*

(HOCHd3P (26)

Trimethylphosphine can be prepared by passing a mixture of hydrogen chloride, methyl chloride, and phosphorus vapous over a charcoal catalyst at 360 "C and subjecting the resulting trimethylphosphonium chloride to alkaline hydr~lysis.~~, 25 The phosphabicyclo[3,3,1Inonane (27) is formed when a mixture of tris(hydroxymethyl)phosphine, formaldehyde, cyanamide, and polyphosphoric acid is kept at room temperature.26 Mislow has prepared optically active arsines by modification of his phosphine ~ynthesis.~' Treatment of the arsinite (28) with organo-lithium reagents gave the optically active arsines directly.

2PrLi

MeAsPr

I

Ph

Condensation of 1-phenylphosphorinan-4-onewith various phenylhydrazones, followed by cyclization in situ with acid, yielded the phosphorinoindoles (29), which quaternize on phosphorus when treated with alkyl halides.28 A series of phenylphosphorino[3,3-dlpyrimidines, e.g. (30), has been prepared from the phenylphosphine (3 l).29 H. Staendeke, Ger. Offen. 2116439/1972 (Chem. A h . , 1973,78,16309). H. Staendeke, Ger. Offen. 2 116355/1972 (Chem. A h . , 1973, 78, 43704). 8 6 D. J. Daigle, A. B. Pepperman, and F. L. Normand, J. Heterocyclic Chem., 1972,9,715. 3 7 J. Stackhouse, R. J. Cook, and K. Mislow, J. Arner. Chem. SOC., 1973, 95, 953. * e K. C. Srivastava and K. D. Berlin, J. Org. Chem., 1972, 37, 4487. ** T. E. Snider and K. D. Berlin, J. Org. Chem., 1973, 38, 1657.

24

as

Phosphines and Phosphoniurn Salts

+

CH(0Et)s

7

-'

Reactions.-Nucleophilic Attack on Carbon. Activated olefins. Phenylphosphine reacts with terminally unsaturated carboxylic esters to yield diesters from which the carbon-phosphorus heterocycles (32) can be prepared by the acyloin condensation in the presence of trimethylsilyl The structure of the adduct formed from the reaction of trialkylphosphines with para-substituted benzylidenemalononitriles has been shown to be a zwitterionic species (33) by the use of high-resolution n.m.r. spectrosc~py.~~

.(33) R = Et or Bu 'O

s1

J. W. von Reijendam and F . Baardman, Tetrahedron Letters, 1972, 5181. C. A. Fyfe and M. Zbozny, CanadJ. Chem., 1972,50, 1713.

0rganophosphorus Chemistry

8

Several 6-oxa-2-phospha-adamantanes,e.g. (34), have been synthesized using a double Michael addition of a primary phosphine to cyclocta-2,7dienone. The resulting ketones were converted into the corresponding alcohols, which were cyclized to (34) with lead tetra-a~etate.~~

oo 4-

PhCH2PH2 + PhCH,#’

O=P-

I

Q

Pb(OAc),

O=P

I

CHzPh

CHtPh

(34) Activated acetylenes. The reaction of diphenylvinylphosphine with dimethyl acetylenedicarboxylate affords either a 1 : 1 adduct or a 1 : 2 adduct depending upon the reaction conditions. Hydrolysis of the adducts The phosphine oxide (35) was also produced gave (35) or (36), re~pectively.~~ by hydrolysis of the zwitterionic adduct obtained from the reaction of trans-1 ,2-bis(dipheny1phosphino)ethylene and dimethyl acetylenedicarboxylate. The authors also confirmed previous that the cis-isomer gives a 1,4-diphosphorin (37). A preliminary account has appeared of the generation of benzyne in the presence of unsaturated phosphine~.~~ The bisphosphine (38) was surprisingly

X

I

PhzP:>

CI

Ql

_.)

X

X = COzMe

8a

GXX

%

PhZ

X

I1

X

I

PhzPCHzCH=CCH2X (35) 23%

xfix

X

I*

0

Ph 2

Y. Kashman and E. Benary, Tetrahedron, 1972, 28, 4091. M. Davies, A. N. Hughes, and S. W. S. Jafry, Canad. J. Chem., 1972, 50, 3625. M. A. Shaw, J. C. Tebby, R. S. Ward, and D. H. Williams, J. Chem. SOC.(C)., 1970, 504.

Phosphines and Phosphonium Salts

9

X

.X

I

ph2pl C

PhaP

+ 11'1 C

I

X

X = C0,Me

(37)

obtained from diphenylvinylphosphineand o-benzenediazonium carboxylate, whereas trans-l,2-bis(diphenylphosphino)ethylene gave the expected ylide (39) when added to N-nitrosoacetanilide in the presence of potassium acetate.

NO

I

NCOMe

Carbonyls. Another report of the preparation of 1,3-0xaphosphorinans (40),by the acid-catalysed condensation of 3-hydroxypropylphenylphosphine with aldehydes and ketones, has appeared.s6 The reaction of diphenylphosphine with hexafluoroacetone gave an adduct, readily oxidized to the phosphine oxide (41), which isomerizes in the presence of base.36Dialkoxyphosphines have been showns7to add in a similar fashion to aldehydes to form the adducts (42). The full report of the inversion of alkene stereochemistry via epoxides and reaction with lithium diphenylphosphide has appeared.38 K. Issleib, H. Oehme, and M. Scheibe, Synth. Inorg. Metal-org. Chem. 1972, 2, 223. A. F. Janzen and 0. C. Vaidya, Canal. J. Chem. 1973,51,1136. N. B. Karlstedt, M. V. Proskurnina, and I. F. Lutsenko, Zhur. obshchei Khim., 1972, 42,2418 (Chem. Abs., 1973, 78,88475). E. Vedejs and P. L. Fuchs, J. Amer. Chem. SOC.,1973, 95, 822.

*I

sB

s8

Organophosphorus Chemistry

10 PhPH(CH2),0H

+

n

R1R2C0 -+

+

H20

PhpXo R1 R2 (40) R1= Et or Ph; RZ = H or Me; R*-RB = (CH,), or (CH2h

0 OH PhzPH

+

(CF3)zCO

-r)

Ph?PC(CF3), I

II I

(01 _+

Ph2P--C(CFS),

/,

OH

pyridine

Ph2P-O-CH(CFS)

II

2

0 (41)

Nucleophilic Attack at Halogen. The halogenation of nucleoside hydroxygroups by reaction with carbon tetrahalides and triphenylphosphine has been studied in some Primary hydroxy-groups react more rapidly than secondary hydroxy-groups, the stereochemistry of the latter reactions depending upon the halide used. An interesting side-product obtained during the bromination of thymidine in DMF with triphenylphosphine-carbon tetrabromide was the bromide (43). In the absence of thymidine the salt (44)was obtained. The reaction of 1,3-distearoylglycero1 with triphenylphosphine-carbon tetrachloride gave the 2-chlorodeoxy-derivative(45) with only a trace amount of the 3-chlorodeoxy-isomer derived from acylo~y-migration.~~ Aldehydes can be conveniently converted into dibromoalkenes (46) by the use of the triphenylphosphine-carbon tetrabromide reagent.41 Chlorination of epoxides with triphenylphosphine-carbon tetrachloride gave cis-l,2dichloroalkanes. Reaction with ( + )-propene oxide showed that inversion of configuration had occurred at both carbon atoms. Bromination using carbon tetrabromide was also successful, but was much less stere~specific.~~ The salts (47) are formed when bis(dipheny1phosphino)amine and carbon tetrachloride are treated with a m i n e ~ Cyclocondensation .~~ to the triazadiphosphorins (48) takes place when bifunctional amidines are used. *@J. P. H. Verheyden and J. G. Moffatt, J . Org. Chem., 1972, 37,2289. 'O

4a 43

R. Aneja, A. P. Davies, and J. A. Knaggs, J.C.S. Chem. Comm., 1973, 1 10. E. J. Corey and P. L. Fuchs, Tetrahedron Letters, 1972, 3769. N. S. Isaacs and D. Kirkpatrick, Tetrahedron Letters, 1972, 3869. R. Appel and G. Saleh, Annalen, 1972, 766, 98.

Phosphines and Phosphonium Salts

11

CHZOCOR

I CHOH

Ph,P-CCI,

F

I CH~OCOR

RCHO

CHZOCOR I ClCH I

Ph,P-CBr,

(Ph2P)aNH

RCH=CBra (463 R = Ph, n-C,H,,, or

+ 2CC11, + 2RNHa

_.f

NH 4 3RC, 3. (Ph2P)BNH NH!4

[RNH-(PhdP-N-P(PhJ-”R]+ C1(47). R = H, But, or PhNH

+ 2CC14

Pha N-P

R-C,

4

‘“

N=P’ Phz (48) R = H, Me, Ph, ‘Me2N,or EtO

In a full paper the authors withdrew their earlier statement that the azirine (49) had been detected by i.r. spectroscopy in the reaction of azirine derivatives (50) with triphenylphosphine-carbon tetrachloride. However, they still

believe that (49) is an intermediate.44 The kinetics of the reduction of or-halogenobenzyl phenyl sulphones (51) with triphenylphosphine have been studied. Although the bromides react substantially faster than the chlorides, the iodides react slower than the bromides, an effect that may be due to the large drop in energy that can be

I4

T.Nishiwaki and F. Fujiyama, J.C.S. Perkin I, 1973, 817.

Organophosphorus Chemistry

12

H I PhSOaC-X

H I + 4- PhsP * [PhSOaq-XPPha]

HO

PhSO&H&

I

3.

Ar

PhsPO

+ HX

gained by bond formation in going from the phosphorus-bromine to the phosphorus-iodine bond.45 Nucleophilic Attack at Other Atoms. Benzoylation of glycosides has been described, using the diethyl azodicarboxylate-triphenylphosphine complex as the activating agent (see Scheme l).4s

Scheme 1

u

0

0

11

II

"p

BuSC ).c.O

II 0

BU

T-O\

2c\c-o/ 0 II

/ PPhs

\

Bu,d ' 0 'C'

+ PhsPO

II

0

(52)

Bu2C=C=0

+ Ph,PO

Treatment of di-n-butylmalonyl peroxide with triphenylphosphine gave an intermediate phosphorane which breaks down to give the malonyl anhydride (52) and di-n-butylketen.47 The stoicheiometry and the rate constants of the reaction of triphenylphosphine with ozone have been measured at various temperatures (see Chapter 10, Section 2).48 45

47 48

B. B. Jarvis and J. C. Saukaitis, Tetrahedron Letters, 1973, 709. G. Alfredsson and P. J. Garegg, Acta Chem. Scand., 1973, 27, 724. W. Adam and J. W.Diehl, J.C.S. Chem. Comm., 1972,797. S . Razumovskii and G. D. Mendenhall, Canad. J. Chem., 1973,51, 1257.

Phosphines and Phosphoniirm Salts

13

Triarylphosphines react with thionyl chloride to give initially the phosphine oxide and sulphur dichloride. Further reaction affords triarylphosphine dichloride and sulphur, or phosphine sulphide, depending upon the ratio of the reactants.4DTriphenylphosphine forms two 1 : 1 adducts with sulphuryl chloride.6oInfrared spectroscopy indicates that one has phosphorus bound to sulphur and the other, more stable, adduct has phosphorus bound to oxygen. Miscellaneous. Linear free energy correlations have been found for the barriers to pyramidal inversion of phosphines with arsines, amines, sulphonium salts, and other species.61The slopes of the correlation lines are a measure of the relative sensitivities of the inversion centres to structural modification. The inversion barriers of a number of phosphines have been reported. They include the acylphosphines (53) and (54),18the silylphosphine (55),62 the triarylphosphine (56),63 and the phosphines (57).64 Me

(PhCH,),PCOCH, (53) 81.9 kJ mol-I

(PhCH2)2COCF3 (54) 67.7 kJmol-’

I ,Si(OMe)S But Si -P Me I ‘SiMe3 (55)

c 43.5 kJmol-l

(Me,CH),P-X (57) X = CN, CH=CHCN, or CH=CHCO,Me > 109 kJmol-l

(56) 134.6 kJ mol-l

The rates of reaction of a series of triarylphosphines with or-bromoacetophenones have been defe~mined.~~ Tris-m-substituted triphenylphosphines react ‘significantly’ faster than predicted from their Hammett 0 values, an effect that the authors claim is due to steric acceleration of the reaction.

‘@ E. H. Kustan, B. C. Smith, M. E. Sobeir, A. N. Swami, and M. Woods, J.C.S. Dalton, 61

6a 68 64

66

1972,1326. A. J. Banister, B. Bell, and F. Leonard, J. Inorg. Nuckar Chem., 1972,34, 1161. R. D. Baechler, J. D. Andose, J. Stackhouse, and K. Mislow, J. Amer. Chem. Sac., 1972,94, 8060. 0. J. Scherer and R. Mergner, J. Organometallic Chem., 1972,40, C64. R. Luckenbach, Phosphorus, 1973,2,293. R. G. Kostyanovskii, Y . I. El’natanov, L. M. Zagurskaya, and K. S. Zakharov, Bull. Acad. Sci., U.S.S.R.,1973,21, 1844. G. B. Borowitz, D. Schuessler, W. McComas, L. I. Blaine, K. B. Field, P. Ward, P. Rahn, B. V. Rahn, W. Glover, F. Roman, and I. J. Borowitz, Phosphorus, 1972,2,91.

14

OrganophosphorusChemistry

The reaction of secondary phosphines with di-t-butylmercury gave high yields of tetraorganodiphosphines via intermediate (58), which was isolated when di-t-butylphosphine was used.66 2RzPH

+ ButzHg

(R2P)zHg RAP2 (58) R = Ph, Et, or But *

1,2-Diphenyldiphosphine has been found6' to exist in equilibrium with pentaphenylcyclopentaphosphine and phenylphosphine when the latter reagents are heated in pyridine at 100 "C:

+

SPhPH, (PhP)5 f 5(PhPH)2 Ring-opening occurs when the bicyclic phosphines (59) are treated with sulphur in boiling benzene.68 Dichloroketen can be generated from the reaction of the trichloroacetates (60) with triphenylpho~phine.~~ Treatment of the tosylhydrazone (61) with sodium amide in toluene gave 1-phenylphosphorin-3-ene and the oxide (62), which arose from oxidation of the phosphine by the tosyl group.6o

CS~*~-p (59)

R = H, Me, Br, or OMe

RSMOCOCCIS -t- PhaP 4R,MCI+ PhsPO f - [Cl~C=C=O] (60) R3M= Me& Bu,Sn, or Me,Sb

6'

3- NaNH,

Ph

ST

6a

7% 00 +

Ph

Ph

M. Baudler and A. Zarkadas, Chem. Ber., 1972, 105, 3844. J. P. Albrand and D. Gagnaire, J. Amer. Chem. SOC.,1972, 94, 8630. E. S. Kozlov, A. I. Sedlov, and A. V. Kirsanov, J . Gen. Chem., (U.S.S.R.), 1972,42,517. T. Okada and R. Okawara, J. Organometallic Chem., 1972, 42, 117. D. L. Morris and K. D. Berlin, Phosphorus, 1972, 1, 305.

Phosphines and Phosphoniurn Salts

15

The chemical shifts of a number of five-membered cyclic phosphines have been measured and discussed in detail (see Chapter 11, Section 1).61 Ab initiu calculations on phosphine using three different Gaussian basic sets, with and without the addition of d-orbitals, have been compared.62 The factors which control the reactivity of cyclic tervalent phosphorus compounds have been discussed in terms of the effect on the ring strain between ground state and the transition The chemiluminescence of lithium phosphides has been studied (see Chapter 10, Section l).64 2 Phosphonium Salts

Preparation.-A comprehensive review of the preparation of phosphonium salts is now available.6s Markl’s method for the synthesis of cyclic phosphonium salts (Scheme 2) has been found to be generally applicable to the synthesis of C-methylated rings.66 7 BrCH2(CH2)XH Br H CCH2Br

+f“ Ph2P-FPh2

__f

21’

Ph,P+- PPh2

J\

Scheme 2

Cyclic phosphonium salts have been made by cyclization of the esters (63) using phenyl-lithi~m.~~ The pKa values of these salts are more than 4 units lower than the corresponding acyclic compounds. + / (CH2) n CO &t

PhZP, CHS (63) O1 O8

66

+

PhLi

.+/ (CH z)nCO 2 E t --+ Ph2P,

CH2-

+/

(CH,)fa\

-+ PhzP\cH,/c=*

J. J. Breen, J. F. Engel, D. K. Myers, and L. D. Quin, Phosphorus, 1972, 2, 55. J.-B. Robert, H. Marsmann, L. J. Schaad, and R. R. Van Wazer, Phosphorus, 1972, 2, 11. R. Greenhalgh and R. F. Hudson, Phosphorus, 1972, 2, 1. R. A. Strecker, J. L. Snead, and G. P. Sollott, J . Amer. Chem. Soc., 1973,95, 210. P. Beck, in ‘Organic Phosphorus Compounds’, ed. G. M. Kosolapoff and L. Maier, Wiley-Tnterscience, 1972, Vol. 2, p. 189. K. L. Marsi, D. M. Lynch, and G. D. Homer, J . Heterocyclic Chem., 1972, 9, 331. G. Aksnes and H. Haugen, Phosphorus, 1972, 2, 155.

16

Organophosphorus Chemistry

7-Methylhexahelicenehas been resolved by conversion to the phosphonium a pure diastereomeric salt of which was obtained by salt formation salt (a), with silver D( -) hydrogen dibenzoyltartrate. Alkaline hydrolysis gave the pure hydrocarbon.sa

i, NBS ii, MesP

N-(Chloromethy1)carboxamide.s readily react with triphenylphosphine to give high yields of the phosphonium salts (65).69 In a related reaction, the ureidomethylphosphonium salts (66) were prepared by displacement of methanol from the corresponding methoxymethylureas with triphenylphosphine in the presence of acid.'Os71 The tosylate group in (67) was displaced dire~tly'~ by triphenylphosphine at 140 "C. RCONHCH2Cl 3. Ph3P -+

RCONHCH2$PhSC1' (65) R = CF3, CC13,or Ph

.O

0

/ \

/ \

It

I1 C

R1-N

I

R2

C

NCH20R1 +'Ph,P

I

'-% R1-N

R'

PhZPCH20Ts

II 0

+ Ph3P

140 "C

I R2

N-CH2hh3

I

R3

X-

-t

PhZPCHzPPh3 OTSII 0

(67)

1,4-Diphosphoniacyclohexadiene systems (68), having an alkyl and a phenyl group on each phosphorus atom, have been synthesized from acetylenic phosphines and hydrogen chloride in cold acetic The exocyclic dienes (69) could be obtained by thermal isomerization of (68). w 71

M. S. Newman and C. H. Chen, J. Org. Chem., 1972,37, 1312. B. S. Drach, E. P. Suridov, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972,42,942. H. Petersen and W. Reuther. Annulen, 1972, 766, 58. H. Petersen, W. Reuther, U.S.P. 3658804/1972 (Chem. Abs.. 1972, 76, 153923). W. Wegener and P. Scholz, 2. Chem.. 1972, 12, 103 (Chem. Abs., 1972, 77, 34627). M. S. Chattha and A. M. Aguiar, J. Org. Chem. 1973, 38, 1611.

Phosphines and Phosphonium Salts

Bu\

17

HCI

PC-CR

ph'

\

R

\

(69)

R = alkyl

Pr

Acetylenic phosphines and bromoketones form 4-phosphoniapyran derivatives (70).74 Cyclic phosphonium salts (71) are also obtained from acetylenic phosphines by reaction with nitrilimine~.~~ Phosphonium salts, e.g. (72), containing a P-P linkage are formed from tertiary phosphines and phosphorus oxy~hloride.~~

;fFfR8

3. R*COCHBrR8

PhPR4C,CR1

R1 (70)

PhzPCECP'

4-

-

+ R'--C=N-N-Ph

t

Et$H C1-

NPh

-

c1-

C=N

(71)

EtaP ,+POCls

Ra B r' R1= Jkyl or aryl

R'. = H, Me,or Ph R2 = P-OSNC~H~, Et02C, or Ph

+

EtaP-PC12 I1 0

c1-

(72) 74

l6

M. Simalty and M. H. Bebazaa, Bull. SOC.chim. France, 1972, 3532. L. A. Tamm, V. N. Chistokletov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1920. E. Lindner and H. Beer, Chem. Ber., 1972, 105, 3261.

Organophosphorus Chemistry

18

A further report on the isolation of diacylmethyltriphenylphosphonium salts (73) by the action of hydrogen chloride or trifluoroacetic acid on the corresponding phosphorane has appeared." The addition of triphenylphosphine to the methyleneiminium salts (74) gave the phosphonium salts (75), which are in equilibrium with the starting materials but can be isolated at low femperat~res.~~ The phosphonium salts (76) are formed in high yield when a solution of phenol and carbon tetrachloride in ethylene dichloride is treated with triphenylphosphine followed by antimony pentachl~ride.~~ Chloramination of some heterocyclic tertiary phosphines with chloramine has been described.*O

Ph,P=C,

/

COMe

COR

[RaN=CH2]+ X-

HX

S

+ Ph3P

I ,COMe Ph3PCH, XCOR (73) X = C1 or CF3C02 R = Ph, Me, or OMe

+ * R2NCH2PPh3

(74)

PhOH

+ CCI4 + Ph3P

X' (75) X = C1 or Br R2N = morpholino or piperidino

SbC15

(PhO$Ph, SbC1,'(76)

Reactions.-Alkaline Hydrolysis. The sterochemistry of the alkaline hydrolysis of the phosphonium salts (77) has been reported.*l The small energy differences between the possible phosphorane intermediates is emphasized by the fact that the reaction, with loss of R, proceeds with partial inversion or retention of configuration depending upon the nature of R and whether the reaction is run under heterogeneous or homogeneous conditions. Me\,,+ Ph-P-R (77) R = PhCH2, p-CF3CBHdCH2, Ph,CH, or CH,CH=CH,

("y) R' R' (78) R = Et or Me n=4or5

T. A. Mastryukova, I. M. Aladzheva, E. I. Matrosov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1461. l o H. Boehme and M. Haake, Chem. Ber., 1972,105,2233. 7 0 H. Teichmann, M. Jafkowski, and G. Hilgetag, J. prakt. Chem., 1972,314, 129 (Chem. A h . , 1972, 77, 152274). S. E. Frazier and H. H. Sisler, Inorg. Chem., 1972, 11, 1431. ** R. Luckenbach, Phosphorus, 1972, 1, 293.

7 p

Phosphines and Phosphonium Salts

19

The alkaline hydrolyses of several tetra-alkylphosphonium salts using potassium hydroxide in aqueous DMSO have been studied.s2 Ring strain is the major factor governing the rate of reaction and the ratio of ring-opened against ring-retained products for the cyclic salts (78). Hydrolysis of the spirophosphonium salt (79) with lithium hydroxide surprisingly gave the rearranged oxide (80) with only a minor amount of the expected

$4 R I

R

R

LiOH

\

I/

R

R (79) R = H or Me R

R

R

4-

R

Q I

I

R

R

There appears to be a small preference for attack of hydroxide ion opposite the bulky menthyl group in the alkaline hydrolysis of the acyclic dialkoxyphosphonium salts (81). The ability of the intermediate phosphorane to undergo pseudorotation as opposed to direct loss of an alkoxide group is determined primarily by the leaving-group ability of the alkoxide. In these reactions when methoxide is in the apical position of the frst-formed phosphorane, pseudorotation is virtually n~n-existent.~~ The results of a study of the stereochemistry of the reaction of the phosphonium tetrafluoroborate (82) with various nucleophiles indicate that there is reversible phosphorane formation in competition with nucleophilic attack at carbon (the product-forming step). There appears to be a correlation 8s B4

K. L. Marsi and J. E. Oberlander, J. Amer. Chern. SOC.,1973, 95, 200. D. Hellwinkel and H.-J. Wilfinger, Chern. Ber., 1972, 105, 3878. K. E. DeBruin and J. R. Petersen, J. Org. Chern., 1972, 37, 2272.

20

Organophosphorus Chemistry

between the classification of the nucleophile as hard or soft and its ability to induce racemization by nucleophilic attack at p h o s p h o r u ~ . ~ ~ Me,, .,OR1

' h P (81)

P \OR2

R1,Re = Me, Et, or Menthyl

OMenthyl Ph,, I .P-OMe

(82)

Z&

Hydrolysis of alkoxy(methy1thio)phosphonium salts, with displacement of the methylthio-group, proceeds with retention of configuration, which is consistent with attack opposite the alkoxy-group to give the intermediate (83) which loses SMe directly from the equatorial position or pseudorotates before losing the SMe from the apical position.as Ph\

~

Ph\ ,OMenthyl

,OMen thy1

/=\

Me SMe SbClc

P

Me/ O \

..

\

OR

Phi I ;P-SMe

Ph\ ,OMe P But' O \ SbCI;

The presence of a ferrocenyl group bonded to phosphorus causes a marked depression in the rate of decomposition of phosphonium salts compared with the phenyl analogue. The effect is attributed to direct interaction between the electrons occupying an hag orbital of the ferrocenyl group and a 3d orbital on phosphoru~.~' The alkaline hydrolysis of 1,2,2,3,4,4-hexamethyI-l-phenylphosphetani~m bromide leads to a ring-expanded oxide, which has been formulated as (84). However, X-ray diffraction of the product obtained by reduction of (84)and quaternization with methyl bromide indicates a structure (85) in which K. E. DeBruin and S. Chandrasekaran, J. Amer. Chem. SOC., 1973,95,974. N. J. De'Ath, K. Ellis, D. J. H. Smith, and S. Trippett, Chem. Comm., 1971, 714. W. E. McEwen, A. W. Smalley, and C. E. Sullivan, Phosphorus, 1972, 1, 259.

21

Phosphines and Phosphonium Salts

(84)

Me Me

o// 'Me

rearrangement of the methyl groups has taken place.88This is very surprising, especially since X-ray diffraction of the product obtained by aromatization of the oxide with palladium+harcoal has been shown to be (86), in which the original methyl sequence has been maintained.8g The exchange of CH2OH groups between tetrakis(hydroxymethy1)phosphonium chloride and the corresponding phosphine in the presence of a limited amount of NaOD (Scheme 3) has been studied using variabletemperature n.m.r. spectrosc~py.~~ 4-

-OD

(HOCH2),P C1- C (HOCH&P

+ CHaO

Scheme 3

Additions to Vinyt'phosphonium Salts. The use of a number of substituted vinylphosphonium salts for the synthesis of heterocyclic compounds has been in~estigated.~~ The phosphonium zwitterion (87) could be isolated from the reaction of isopropenylmethyldiphenylphosphoniumbromide with sodium salicyloxide. /I-Acylvinylphosphonium salts react with diazomethane to form ylides which yield 4-acylpyrazoles (88) upon addition of potassium hydroxide.92

91

J. N. Brown, L. M. Trefonas, and R. L. R. Towns, J. Heterocyclic Chem., 1972,9,463. Mazha-ul-Haque, J . Chem. Soc. (B)., 1970, 71 1 . S. E. Ellzey, jun., W. J. Connick, jun., G. J. Boudreaux, and H. Klapper, J. Org. Chem., 1972, 37, 3453. E. E. Schweizer, A. T. Wehman, and D. M. Nycz, J. Org. Chem., 1973,38,1583. E. Zbiral and E. Bauer, Tetrahedron, 1972, 28, 4189. B

22

Organophosphorus Chemistry BrPh2P-C=CH2 +

I

I

aCHO '

+

+

0-

Me Me

CH=CH

+/

Ph2P \

Me

(87)

+

+ CH2Na

Ph,P-CH=COR

+

+ PhSP-CH-CHCOR

I

\

NkN,CH2

HqcoR + t

KOH

PhJQ

N\N H (88) R = Me or Ph

Ph,P=C-C-COR /
In the full reportg3 of the condensation of vinylphosphonium salts (89) with nucleosides and nucleoside bases, the structure of the initial adduct has been shown to be (90).

+

Ph$-CH=CH-COR1

+

(89)

R2/ (90) R1= H or Me R2 = H, Me, ribose, or triacetylribose

(Pyrrolylmethy1)phosphonium salts (91) can be prepared from /?-acylvinylphosphonium salts (92) and @-enaminocarbonylcompounds. The addition of various nucleophiles to these salts gave good yields of pyrr01es.~~ Similarly, the imidazoles (93) can be prepared starting from amidines. The phosphonium salts (94), formed from (prop-2-yny1)triphenylphosphonium bromide and aromatic aminocarbonyl compounds, can be converted to substituted quinolines by the addition of sodium h ~ d r i d e (Prop-2-yny1).~~

85

E. Hugl, G. Schulz, and E. Zbiral, Annalen, 1973, 278. E. Zbiral and E. Hugl, Phosphorus, 1972, 2, 29. E. E. Schweizer, C. S. Kim, C. S. Labaw, and W. P. Murray, J.C.S. Chem. Comm., 1973, 7.

23

Phosphines and Phosphonium Salts

+ MeC=CHCOR2

Ph3fCH=CHCOR'

_.f

I

Ph36-eH-CHCOR1 I

NH2

~HCOR~

I + I Me

C=NHB

YCH2

H2Y c"

R1

I

R20C \ R20C

Me

Ph3P--CHe

Y-

t

R20C \ NH

Me

(91)

R1 = Ph or Me, R2 = OEt or Me, Y = CN or (EtO,C),CH

(92)

+ R3-C

HNH \

NH2

-

+

Ph,P-CH2MR1 N\

~

NH

YCH2MR N\

NH

Y R3

Y R3

(93) R3 = Ph or SMe

triphenylphosphonium bromide can also be converted into N-substituted iminotriphenylphosphoranes( 9 9 , which are useful reagents for the preparation of some heterocyclic Thus an intramolecular Wittig reaction gave a pyridazinylphosphonium bromide (96), and formation of a stabilized ylide followed by addition of an aromatic aldehyde gave the pyrazole (97).

HCfC-CH2PPhS +

4-

acoR ocoR ' //CHpph8 +

I_f

\

NH-C,

NH2

Me (94) R = Ph or OMe

R I

24

0rganophosphorus Chenztisry

Miscellaneous. Selective dehydration of secondary alcohols, such as trans-2methylcyclohexanol, without rearrangement and with a high predominance of the Saytzeff product, can be carried out using methyltriphenoxyphosphonium iodide in HMPT. Primary alcohols are converted into the expected iodides.gs Treatment of the phosphonium salt (98) with lithium-HMPT in the presence of benzaldehyde, or with sodium and benzophenone in THF, afforded moderate yields of Wittig products that possibly arise from a cyclic bi~ylide.~' Low-temperature n.m.r. studies indicate that triphenylalkylphosphonium salts (99) are able to adopt a chiral propeller conformation in $.

HCrC-CHzPPh,

+ PhiP=NR

4-

ct

PhaPCHa-CCH=PPh3

II NR

(95) R = CHCOMe, CHCOPh, or N=CHCOPh

(95)

R = N=CHCOPh

q*co, N-N=CHCOPh

II

Me-C-CH=PPh3

CH&OPh (97)

The barrier between enantiomeric conformations, due to H-H repulsion, is about 38 kJ mol-l. Azido-bromo-compounds (100) are obtained when the phosphonium salts (101) are diazotized using ethyl nitriteeg9 There appears to be a critical angle at phosphorus for phosphonium salts in their reactions with phenyl-lithium below which they form phosphoranes, e.g. (102), and above which ylides are produced, e.g. (103).100 R. 0. Hutchins, M. G. Hutchins, and C. A. Milewski, J. Org. Chem., 1972, 37, 4190. E. Vedejs and J. P. Bershas, J. Org. Chem., 1972, 37, 2639. J. M. Brown and K. Mertis, J. Organometallic Chem., 1973, 47, C5. E. Zbiral and E. Keschmann, Annalen, 1972, 758, 72. l o o E. W. Turnblom and T. J. Katz, J.C.S. Chem. Cornm., 1972, 1270. @I 87

Phosphines and Phosphonium Salts

25 P

h

Ph w

Li-HMPT or Na-THF'

~

Ph Ph

The salts (104) have an enolic structure in the solid state but in solution an equilibrium exists with the keto-form.lol

3 Phosphorins Preparation.-The methylenephosphacyclohexadiene (105), formed quantitatively from diphenylketen and the corresponding ketone, was converted lol

T. A. Mastrgukova, Kh. A. Suerbaev, P. V. Petrovskii, E. I. Matrosov, and M. I. Kabachnik, Zhur. obshchei Khim.,1972,42,2620 (Chem. Abs., 1973,78,110416).

Organophosphorus Chemistry

26

PhzCCHaPh I

into the phosphine (106) by salt formation using phosphorus pentachloride followed by reduction with phenylsilane.lo2The phosphine (106) rearranged thermally to the phosphabenzenes (107). This thermal rearrangement has been shown to be an intermolecular radical process by crossover experiments and thermolysis in the presence of diben~ylmercury.~ O3 A 2-phosphanaphthalene(1 08) has been prepared from diethyl benzylphosphonite (Scheme 4). Reaction of the secondary phosphine with phosgene 0

'OH

Br

I

Reagents: i, MeCHCOzEt; ii, HCI-HzO; iii, (HPOdn;iv, NaBH4; vi, COC12; vii, DBU.

Scheme 4 lo' lo8

G . Mark1 and D. E. Fischer, Tetrahedron Letters, 1972,4925. G . Mark1 and D. E. Fischer, Tetrahedron Letters, 1973, 223.

V,

HaSW

27

Phosphiiies aird Phosphonium Salts

Br

l i i , iii

a< a / iv, iii

PhCHSJ

\ CHgPh ph

PhCHa/

\CHgPh Ph

COPh I

Ph

Reagents: i, KOBut; ii, H3P04;iii, NaOH; iv, C&I; v, PhCOCl.

Scheme 5

produced an unstable chlorophosphine which when treated with DBU gave (108) as a white crystalline solid.lo4 The phosphonium salt (109) can be cyclized to (110) by treatment with potassium t-butoxide. Bromination followed by dehydrobromination (Scheme 5) gave the stable phosphanaphthalene (111). The addition of methyl iodide to (111) gave a phosphonium salt which deprotonates in base to give (112). Benzoyl chloride gave the 4-benzoyl derivative dire~t1y.l~~ Hydrolysis of (1lo), followed by bromination and dehydrobromination (Scheme 6), afforded the phosphine oxide (113) which on reduction and thermal cleavage gave 2-phenyl-1-phosphanaphthalene.log The 4-phosphoniapyran (114) in acetic acid gave a diketone which with ammonium acetate gave (115) (Scheme 7). Reduction of the perchlorate with sodium hydride gave the azaphosphabenzene (116), shown to be aromatic by n.m.r. and U.V. In a similar way the diketone (117), when H. G . de Graaf, J. Dubbeldon, H. Vermeer, and F. Bickelhaupt, Tetrahedron Letters, 1973,2397. l o & G . MHrkl and K.-H. Heier, Angew. Chem. Internat. Edn., 1972, 11, 1016. l o * G. Mark1 and K.-H. Heier, Angew. Chem. Internat. Edn., 1972, 11, 1017. lo' M. H. Mebazaa and M. Simalty, Tetrahedron Letters, 1972, 4363.

- rnPhi& aph

28

Organophosphorus Chemistry

(110)

PhCH( O\

,p\ PhCHz

Ph

0

(1 13) Reagents: i,

NBS; ii, LiBr-DMF; iii, HSiCla; iv, A Scheme 6

treated with ammonium carbonate, yielded an aza-oxic,: which cou ,e reduced with phenylsilane. Thermolysis proceeded in the expected way to give 2,6-diphenyl-1-aza-4-phosphabenzene (118). This compound reacts with organometallics and weak nucleophiles by addition at phosphorus.1o8

Reagents: i, MeC02H; ii, MeC02NH4; iii; NaH-DMSO; iv, (NH&C03; PhSiH3; vi, A; vii, RLi; viii, H2O or ROH. Scheme 7

Reactions.-1 -Fluoro- or 1-alkoxy-phosphorins are obtained from 2,4,6-trisubstituted phosphorins (119) and a variety of arenediazonium tetrafluoroborates. The intermediate radical-cations of the phosphorins were detected by e.s.r. lo*

G. MBrkl and D. Matthes, Angew. Chem. Internat. Edn., 1972, 11, 1019. 0. Schaffer and K. Dimroth, Angew. Chem. Internat. Edn., 1972, 11, 1091.

loB

29

Phosphines and Phosphonirm Salts

R2’

ArNa+BF4-

R2

Ph .

PhQ P h

R2 (119) R1 = Me or Ph RB= But or Ph

Ph

Ph

3P h P.o P h RH, P h o P h x’ ‘x (120)

R’

‘R

R = alkoxy or dialkyamino X = Cl or Br

2,4,6-Triphenylphosphorinand one mole equivalent of bromine or chlorine in the presence of light gave 1,l-dihalogenophosphorins(120). Halide ion can be displaced from these molecules by nucleophiles.l1° One of the crystalline products isolated from the oxidation of 2,4,6-triphenylphosphorin with oxygenlll is the peroxy-compound (121). Oxidation with hydrogen peroxide gave (122).

110

H. Kanter and K. Dimroth, Angew. Chem. Internat. Edn., 1972, 11, 1090. A. Hettche and K. Dimroth, Chem. Ber., 1973, 106, 1001.

Organophosphorus Chemistry

30

Phosphorins have been found to have quite strong donor properties in some circumstances and form numerous complexes via the phosphorus lone-pair.l12 The photoelectron spectrum of phosphabenzene has been compared with those obtained for pyridine, arsabenzene, and stibabenzene and the orbital sequence deduced.lla 4 Phospholes The number of papers in this field has risen sharply this year. This is probably due in part to the methods of synthesis now available, which make these compounds readily available. Papers have appeared in which evidence, obtained by physical measurements, for and against some degree of aromatic stabilization of phospholes is presented. Preparation and Reactions.-A series of phospholes, e.g. (123), has been made by dehydrohalogenation of 3,4-dibromophospholanes or l-halogenophospholenic halides.ll* Their rates of reaction with benzyl bromide vary with the substituents on carbon. 3,4-Dimethylphospholes quaternize readily to form monomeric salts, whereas phospholes without a C-substituent form dimeric salts (124).l151 -Benzyl-3,4-dimethylphospholehas sufficient reactivity to form a nickel chloride salt.ll6 1-Phenyloctafluorodibenzophospholehas been obMeO&

Me0,C

Me0,C

)TJH% HJ=)

I

Me

Me

Br-

/ \

DBU,

uH I

Br

Me

(123)

+ PhCHzBr

-+

%

-

I

R PhCH,/ \R (124) R = PhCH, or PhCHzCHz M. Fraser, D. G . Holah, A. N. Hughes, and B. C. Hui, J. Heterocyclic Chem., 1972, 9, 1457. 11* C . Batich, E. Heibrommer, V. Hornung, A. J. Ashe, D. T. Clark, U. T. Cobley, D. Kilcast, and I. Scanlon, J. Amer. Chem. SOC.,1973, 95, 928. 11' L. D. Quin, S. G . Borleske, and J. F. Engel, J. Org. Chem., 1973,38, 1858. 116 L. D. Quin, S. G. Borleske, and J. F. Engel, J. Org. Chem., 1973, 38, 1954. 110 L. D. Quin, J. G. Bryson, and J. F. Engel, Phosphorus, 1973,2,205.

llP

Phosphines and Phosphonium Salts

31

tained from octafluoro-2,2'-dilithiodiphenyl and dichlor~phenylphosphine.~~~ The phenyl group attached to phosphorus in phospholes (125) can be displaced by t-butyl-lithium.lls In the same paper it was shown that trifluoroacetic acid, followed by neutralization, converts phospholes into the corresponding 3-phospholen oxides (Scheme 8).

R

yJMe - qjMe R

ButLi

t

I

But

Ph (1251 R = Me or H

Me

wMe

Me

Me i, CF,CO,H ii, OH-

*

'R O\

R R = But or Ph

Scheme 8

Phospholes react with benzoyl chloride to yield acylphosphonium salts, which on hydrolysis ring-expand to (126). Further ring expansion was accomplished by treatment with sodium hydride.ll@

(rjR1+R1c$R1

R'.

PhCOCI

RI'

a

*

/ \

R' C1-COPh

(126) R1= H or Me R2= Me or Ph 11'

118

11*

R. D. Chambers and D. J. Spring, J. Fluorine Chem., 1972, 1, 309 (Chem. Abs., 1972, 76, 153848). F. Mathey, Tetrahedron, 1972, 28,4171. F. Mathey, Tetrahedron, 1973, 29, 707.

32

Organophosphorus Chemistry

The reaction of 1,2,5-triphenylphospholewith azides gave the phospholimines (127). These compounds are thermally stable with the exception of N-(o-nitrophenyl)-l,2,5-triphenylphospholimine, which decomposes in boiling mesitylene to give 1,2,5-triphenylphospholeoxide and the benzofuran (128).120 Two isomeric [4+2] adducts have been obtained from the addition of 3,4-dimethyl-l-phenylphosphole sulphide (1 29) and tropone.121

Q

Ph \ P=O

Me

+

0

Physical Measurements.-The electronic structure of phospholes has been investigated using extended CND0/2 calculations and comparisons made with arsoles and pyrroles.122The degree of aromaticity of seven phospholes has been determined on the basis of 31Pand lH n.m.r. Reaction withn-butyllithium resulted in nucleophilic attack on the phosphorus atom and on the double bonds, a result thought to be due to enhanced conjugation between the phosphorus atom and diene The 13C n.m.r. spectrum of 1phenylphosphole indicates some degree of electron delocalization (see Chapter 11, Section l).124 J. I. G. Cadogan, R. Gee, and R. J. Scott, J.C.S. Chem. Comm., 1972, 1242. Y. Kashman and 0. Awerbouch, Tetrahedron, 1973, 29, 191. lPa H. L. Hase, A. Schweig, H. Hahn, and J. Radloff, Tetrahedron, 1973, 29, 469. l p 3 F. Mathey and R. Mankowski-Favelier, Org. Magn. Resonance, 1972, 4, 171 (Chem. A h . , 1972, 77, 19040). la4 T. Bundgaard and H. 3. Jakobsen, Tetrahedron Letters, 1972, 3353. 110

la1

Phosphines and Phosphonium Salts

33

Comparison of the photoelectron spectrum of 1-phenylphosphole with that of 1-phenylphospholan and the spectrum of 2,5-dimethyl-l-phenylphosphole with that obtained for 2,5-dimethyl-l-phenylphospholanshows that the lone pairs in the phospholes take no part in cyclic five-membered conjugation.125 There is also no conjugative effect between the five- and six-membered rings in any of the compounds. Therefore phospholes consist of localized diene systems and lone pairs of phosphorus atom electrons in their ground state, i.e. they are not aromatic.

lz6

W. Schafer, A. Schweig, G . Markl, H. Hauptmann, and F. Mathey, Angew. Chem. Internat. Edn., 1973, 12, 145.

2 Quinquecovalent Phosphorus Compounds BY

S.TRIPPETT

1 Ligand Reorganization and Structure

The role of quinquecovalent intermediates in displacement reactions at phosphorus has been critically reviewed.l It is clear that more understanding of those factors determining the relative stabilities of quinquecovalent phosphoranes and the barriers to their interconversions is required before a comprehensive rationalization of this area of chemistry will be possible. Although data on the relative apicophilicities of groups and the strain factors associated with small rings continue to accumulate, a major obstacle both to the reliability of these data and to their application to discussion of ligand reorganizations in phosphoranes is the continuing uncertainty over the precise details of these processes. No new evidence for the turnstile rotation (TR) process has appeared during the year under review and most workers continue to use the Berry pseudorotation (BPR) process for discussion of their results. Ligand reorganization leading to racemization of the phosphoranes (2) formed in parasitic equilibria during demethylation of the menthoxymethoxyphosphonium salt (1) has been invoked2 to account for the loss of stereospecificity observed with some nucleophiles. Me \pH?

Ph’ ‘OR

Me 4- MeNu t

‘6’

Ph’

OMe

+ Nu-+

‘OR (1 1

?>Me

Me-P

I ‘Ph

NU (2)

R = (-)-Menthy1 Analysis of the variable-temperature 19Fn.m.r. spectrum of (NH,),PF, showed3 that rotation about the two PN bonds is essentially uncorrelated. The activation energy for rotation, 46.6 kJ mol-l, gave a minimum value for PN n-bonding in this molecule. The same authors concluded that although the barrier to PN rotation in the phosphoranes R,NPF4 probably makes a

a

P. Gillespie, F. Ramirez, I. Ugi, and D. Marquarding, Angew. Chem. Znfernaf.Edn., 1973, 12, 91. K. E. DeBruin and S . Chandrasekaran, J. Amer. Chem. SOC.,1973, 95,974. E. L. Muetterties, P. Meakin, and R. Hoffmann, J . Amer. Chem. SOC.,1972,94, 5674.

34

Quinquecovalent Phosphorus Compounds

35

major contribution to the observed BPR barrier, it is not possible to disentangle these two processes. A point-on-a-sphere variant of Gillespie-Nyholm theory has been applied4 to calculation of the BPR barriers in phosphoranes. A value of 19.2-23.8 kJ mo1-1 was obtained for PF,. The possibility that bimolecular intermediates, formed either from two molecules of phosphorane or from phosphorane and solvent, could be involved in ligand reorganization has been emphasized.6 However, the observations that fluorine exchange in Ph,PF is intramolecular when monitored by n.m.r. in Teflon tubes but intermolecular in Pyrex suggests that the intermolecular processes observed here and in related cases' may be due to traces of impurities. Ab initio calculations8 on the reaction of H- with silane and CNDO calculations on substituent effects and ligand reorganization processes in SiH,-nXn species have given results entirely analogous to those previously obtainede on similar phosphorus compounds. X-Ray analysis9 of the spirophosphorane (3) shows it to be essentially trigonal bipyramidal with both oxygens apical, but the tetrathiospirophosphorane (4) is reportedlo to have a geometry intermediate between trigonal bipyramidal and square pyramidal.

0 HN-P, , P

2 Acyclic Systems The variable-temperature lH and 1°F n.m.r. spectra of tetrafluorophosphoranell show that below - 120 "C there are, on the n.m.r. timescale, two different fluorine environments of equal abundance. This implies that the pseudorotation (5) + (6) has AG* > 29 kJ rnol-l, which would be the highest barrier yet observed between topomeric phosphoranes. Details have appeared l2of the preparation and low-temperature 1°F n.m.r. L. S. Bartell and V. Plato, J. Amer. Chem. SOC.,1973, 95, 3097. J. I. Musher, Tetrahedron Letters, 1973, 1093. ' C. G . Moreland, G . 0. Doak, and L. B. Littlefield,J. Amer. Chem. SOC.,1973,95,255. ' T. A. Furtsch, D. S. Dierdorf, and A. H. Cowley, J . Amer. Chem. SOC., 1970,92, 5759. (a)D . L. Wilhite and L. Spialter, J. Amer. Chem. SOC.,1973, 95, 2100; (b) A. Rauk, L. C. Allen, and K. Mislow, ibid., 1972, 94, 3035. * M. Sanchez, J. Ferekh, J. F. Brazier, A. Munoz, and R. Wolf, Roczniki Chem., 1971, 45, 131. l o M. Eisenhut, R. Schmutzler, and W. S. Sheldrick, J.C.S. Chem. Comm., 1973, 144. l1 A. H. Cowley and R. W. Braun, Inorg. Chem., 1973,12,491. I * R. G. Cavell, R. D. Leary, and A. J. Tomlinson, Inorg. Chem., 1972,11,2578.

Organophosphorus Chemistry

36

CF3

(CF,),PO 3- (Me,Si),O

-+- F,C--P,

I ,,0SiMe3 I OSiMe,

CF3 (7)

R'PF4 I- Me,SiOR2 -+ R1PF3(OR2)+ Me,SiF (8)

of the phosphorane (7). At - 140 "C the signals due to the apical CF3groups show additional splitting which could be due to restricted rotation of these groups, caused in turn by restricted rotation round the PO bonds. The thermally stable monoalkoxyfluorophosphoranes (8 ; R1= Me or Ph) have been obtained as shown when R2is either an electron-attractinggroup or isobutyl or ne0penty1.l~The barrier to equivalence of the fluorines (ca. 52.3 kJ mol-1 with R2= CH,CCl,) has been contrasted to the higher barriers (> 63 kJ mol-l) found in analogous amino- and alkylthio-derivativesand has been attributed to the high electronegativity of the alkoxy-group. However, in the pseudorotations (9)7-?(11) leading to equivalence of the fluorines, the high-enery y phosphorane in all cases is (10) and the barrier might therefore be expected to be independent of the nature of the substituent X. The preparation and 19Fand 31Pn.m.r. of the phosphoranes (12) have been described.l* Full accounts have appeared of the preparations and properties la

D. U. Robert, G. N. Flatau, C. Demay, and J. G. Riess, J.C.S. Chem. Comm., 1972, 1127.

M. J. C. Hewson and R. Schmutzler, 2. Naturforsch., 1972, 27b, 879.

37

Quinquecovalent Phosphorus Compounds

of the fluoro- 15, alkoxy-, l6 and aryloxy-phosphoranesl6 R13MePX (X = F, OR2, or Oh). 35Cl N.q.r. of the chlorophosphoranes CC13PCl,, (CCl,),PCl,, and (CC13)2PC12NH2shows1’ that in all cases the trichloromethyl groups are apical; J(16NH)in the last compound is consistent with sp2-hybridizednitrogen. 3 Three-membered Ring

The azine (13) reacts with trialkyl phosphites and with trisdimethylaminophosphine to give 1 : 1 adducts of considerable thermal stability, formulated as the phosphoranes (14) on the basis of their lH and leFn.m.r. and their i.r. (CFJ&=N-N=C(CF3)2

+ R3P

(13)

(CF3)2C--N--N=C(CF&

‘4 R3

(1 4) and mass spectra; no 31Pn.m.r. data were given.l8These are the first quinquecovalent phosphoranes reported in which the phosphorus is part of a threemembered ring.

4 Four-membered Rings Two mechanisms have been proposedl9for the decomposition of the phosphite ozonides (15) to give phosphate esters and singlet oxygen. The preferred route is via the phosphorane (17), formed by pseudorotation of the initial ring-

0 I

(1 8)

(1 9)

H. Schmidbauer, K.-H. Mitschke, W. Buchner, H. Stuhler, and J. Weidlein, Chem. Ber., 1973, 106, 1226. l 8 H. Schmidbauer, H. Stuhler, and W. Buchner, Chem. Ber., 1973,106, 1238. l7 E. S. Kozlov S. N. Gaidamaka, G . B. Soifer, Y. N. Gachegov, and A. D. Gordeev, J . Gen. Chem. (U.S.S.R.), 1972, 42, 748. l 8 K. Burger, J. Fehn, and W. Thenn, Angew. Chem. Internat. Edn., 1973, 12, 502. L. M. Stephenson and D. E. McClure, J. Amer. Chem. Soc., 1973,95,3074. l5

38

Organophosphorus Chemistry

opened species (16). The rate of decomposition by this route is affected by substituents; in general, the less apicophilic the apical RO group in (16), the faster the reaction. If, however, the phosphorus is part of a five-membered ring, e.g. (18), then pseudorotation of the initial ring-opened species (19) to a phosphorane analogous to (17) becomes a high-energy process because of the need to force the ring into a diequatorial position. In these circumstances a relatively slow decomposition of (19) occurs, the rate of which is insensitive to substituents. The Witting intermediate (20) has been assigned a 1 ,Zoxaphosphetan structure20on the basis of its positive 31Pchemical shift. Above 5 “C it gave the expected cyclo-octene and phosphine oxide.

BF4-

(20) 31P e62.8 p.p.rn.

The bicyclic phosphoranes (24; X = O or S) were obtained21 from the tervalent phosphorus compounds (21 ; X = 0 or S) and hexafluoroacetone (HFA) via the cyclic iminophosphoranes (22). Diphenylvinylphosphine similarly gave the 1,2-oxaphosphetan (23). The phosphoramidite (25) with HFA gave the 1,3,2-0xazaphosphetan (26), the intermediate iminophosphorane being formed in this case by proton transfer in the initial adduct.

HFA

(Ph0)zPNHPh (25)

HNPh (Ph0)ZP \OCH(CF3)2

HFA

O--C(CF3)2

I I

OCH(CF3)z (26)

ao

I

(PhO),P-NPh

E. Vedejs, K. A. J. Snoble, and P. L. Fuchs, J . Org. Chern., 1973, 38, 1178. E. Duff, P. J. Whittle, and S. Trippett, J.C.S. Perkin I, 1973, 972.

QuinquecovalentPhosphorus Compounds

39

The variable-temperature lSFn.m.r. of the diazadiphosphetidines (27)--(29) prepared as shown are consistent 23 with concerted pseudorotation at the two phosphorus atoms. Me

Me /N \

3 MeLi

/PF,

F,P\

/

N Me

2MePF,

+

,PFMe, N

Me Me N MeF,P, /PF2Me

\

MeF,P,

N

/ \

N

Me (27)

Me N \ PhF,P, /PF2Ph -+ N Me /

+ MeN(SiMe,),

3- PhN(SiMe,),

Me N \ 2MeF,P ,PFIPh \ N Me (28) Me N / \ --+ MeF,P, P F 2 M e N Ph (29) /

The diazadiphosphetidine (30) dimerized23when kept at 130 "C for seven days. The dimer soluble in carbon tetrachloride was formulated as the cubane-like molecule (31) and the insoluble portion as the salt (32). Vacuum sublimation of the latter gave a tricyclic compound thought to be (33). (MeNPF,),

-% (MeNPF8)4

(30)

5 Five-membered Rings

Phospholans and Phospho1ens.-Whereas the strained phosphonium salt (34) with phenyl-lithium gave24the stable quinquecovalent phosphorane (39, the relatively unstrained salt (36) with the same reagent gave only the ylide (37). pp

0. Schlak, R. Schmutzler, R. K. Harris, and M. Murray, J.C.S. Chem. Comm., 1973,23. K. Utvary and W. Czysch, Monatsh., 1972,103,1048. E. W. Turnblom and T. J. Katz, J.C.S. Chem. Comm., 1972, 1270.

OrganophosphorusChemistry

40

Cyclo-octa-l,5-diene and triphenylphosphine were formed on thermolysis of (35).

6 '6 +

+

Ph,P

Br-

__t PhLi

Fragmentation of the cis-3-phospholen (38) gave25a trans,trans-hexa-2,4diene. The reaction was 99% stereospecific and is probably a concerted disrotatory process, as is the corresponding addition of halogenophosphines to d i e n e ~ . ~ ~ * Attempts to detect asymmetric induction in the reaction of the (inactive) phosphonium ion of the optically active salt (39) with 2,2'-dilithiodiphenyl were Similarly, the optically active salt (40) with bromine gave racemic phosphorane (41). The rates of reaction of the o-phenylene phosphonites (42) with butadiene 27 were in the order H>ClzMe%Me,N and were some 80 times greater than for the corresponding ethylene phosphonites. Hydrolysis of the phosphoranes (43; R = H or Me, X=Cl) gave high-boiling compounds regarded as the hydroxyphosphoranes (44) ; acetylation of the analogous compound (44;R or X = H) gave a diacetate formulated as (45). No slP n.m.r. data were given.

1,3,2-Dioxaphospholans.-The equilibria between the spirophosphoranes (46) and the corresponding phosphites (47) have been studied28 at 100 "C. In general the quinquecovalent form is stabilized by substitution of the rings by methyl or phenyl. With unsymmetrically substituted phosphoranes the less*I

*a

aa

(a) C . D. Hall, J. D. Bramblett, and F. F. S. Lin, J. Amer. Chem. SOC., 1972, 94, 9264; (b) A. Bond, M. Green, and S. C. Pearson, J. Chem. SOC.( B ) , 1968,929. D. Hellwinkel and H. J. Wilfinger, Phosphorus, 1972, 2, 87. F. V. Bagrov, N. A. Razumova, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1972,42, 782. D. Bernard, C. Laurenco, and R. Burgada, J. Organometallic Chem., 1973,47,113.

Quinquecovalent Phosphorus Compounds

41

' p =

p+ p-

2p-

p+ p-

(39)

bI+

blx

Reagents : i, 2,2'-dilithiodiphenyl;ii, 2'PtI-

MeCOCIJAr = Ph,R = H

$

3

0

OCOMe

OCOMe

Organophosphorus Chemistry

42

substituted ring opens preferentially. The unsubstituted bisethylenephosphorane is present to the extent of only 50% at 100 "C. For an account of phosphoranyl radicals derived from spirophosphoranes and from other species, see Chapter 10. 1,3,2-Dioxaphospholens.-New 1,2-dicarbonyl compounds used in the formation of quinquecovalent phosphoranes include the o-quinones (48) 29 and

(50)

(51)

(49)30 and perfluor~biacetyl.~~~ 32 Variable-temperature 19Fn.m.r. studies32 on the adducts from pefluorobiacetyl have given data on the energetics of the required to make the CF groups equivalent pseudorotations (50) ;-'(51) when A is more apicophilic than B and hence on the relative apicophilicities of a range of groups A and B. The trimethyl phosphite-biacetyl adduct (52) did not react with isothiocyanates, but with acyl isothiocyanates gave33 the 2-oxazoline-4-thiones(54), presumably via the intermediate betaines (53). With 2-thiazoline-4,Ediones (55) the adduct (52) gave carbon monoxide, trimethyl phosphate, and the thiazolones (57). The carbon monoxide is probably formed by fragmentation

'0

s1

aa

M. M. Sidky and F. H. Osman, J. Chem. U.A.R., 1 9 7 1 , 1 4 , 2 2 5 (Chem. Abs., 1972,77, 139 898). M. M. Sidky, M. R. Mahran, and L. S. Boulos, J. Indian Chem SOC., 1972,49,383. F. Ramirez and H. J. Kugler, Phosphorus, 1973, 2, 203. J. I. Dickstein and S. Trippett, Tetrahedron Letters, 1973, 2203. F. Ramirez, V. A. V. Prasad, and H. J. Bauer, Phosphorus, 1973, 2, 185.

43

Quinquecovalent Phosphorus Compounds

of the intermediates (56) as shown. Reaction of the trimethyl phosphite-biacetyl adduct (52) with ethylene glycol to give the spirophosphorane (58) is exothermica4to the extent of about 8 kJ mol-l. Me Me

m M 0 o, + O N Q P R

0,

@Me),

I

(53)

(52)

+ (HOCHha

(59)

__f

’’ F. Ramirez, K. Tasaka, and R.Hershberg, Phosphorus, 1972, 2.41.

OrganophosphorusChemistry

44

The phosphorane (59) fragments 2Sasterospecifically to trans,trans-hexa-2,4diene and the phosphonite (60) with AG*-105 kJ mol-I. This activation energy was explained in terms of the need to place the phospholen ring diequatorial before the fragmentation becomes a symmetry-allowed process. However, Hoffmann’s reasoning35applied to this case shows that the allowed process for loss of diene is from an apical-equatoriaI position. 1,Z-0xaphosphoIens.-Methyl vinyl ketone reacts 60 times faster with the ethylene phosphonite (61) than it does with the o-phenylenephosphonite (62),

as expected if the phosphonites are acting as nucle~philes.~~ The spirophosphoranes (64; R = H or Me) have been obtained3’ from the six-membered cyclic phosphite (63) and both acrolein and methyl vinyl ketone. The nonequivalence of the methylene protons of the oxaphospholen ring in the n.m.r. spectrum of (64; R=Me) at room temperature led to the suggestion that OMe

(63)

(64)

R

= H o r Me

pseudorotation in this compound is slow under these conditions. However, the lack of symmetry in this molecule precludes these protons from becoming equivalent by normal pseudorotation processes.

1,3,2-Oxazaphospholens.-Improved preparations of the spirophosphoranes derived from ephedrine and norephedrine have been described.38The effects of substituents on the positions of the equilibria between the spirophosphora6

36

87

38

R. Hoffmann, J. M. Howell, and E. L. Muetterties,J. Amer. Chem. SOC.,1972, 94, 3047. N. A. Razumova, M. P. Gruk, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2109. B. A. Arbuzov, Y. M. Mareev, V. S. Vinogradova, and Y. Y. Samitov, Doklady Chem., 1973, 205, 618. R. Contreras, R. Wolf, and M. Sanchez, Synth. Znorg. Metal-org. Chem., 1973,3, 37.

Quinqueco valent Phosphorus Compounds

45

anes (65), (66), and (67) and the corresponding ring-opened species, e.g. (68), have been studied.SgThe unsaturated ring and aryl substituents favour the quinquecovalent form so that there is no evidence for the tervalent form in solutions of the phosphorane (69). H

Me

Me

(67)

(69) The bicyclic phosphoranes (70), obtained as shown, exist entirely in the quinquecovalent form in

(70)

R

= Me or 3,4-Me2C,H,

The spirophosphoranes (71) and (72) derived from ( - )-ephedrine equilibrate in solution by a process involving five successive pseudorotations. The

(71) a@ ‘O

(72)

C. Laurenco and R. Burgada, Compt. rend., 1972,275, C, 237. D. Houalla. J. F. Brazier M. Sanchez and R. Wolf Tetrahedron Letters. 1972.2969.

Organophosphorus Chemistry

46

isomer (71) is obtained in a pure state on crystallization and its mutarotation has been followed in benzene solution at different ternperat~res,~~ leading to activation parameters for the conversion of (71) into (72) of AG*=99.1 kJ mol-l, AH*= 95.3 kJ mol-l, and AS* z 13 J K-l mol-l. These agree with data previously obtained from n.m.r. studies. The quasi-enantiomers (73) and (74), containing one (-)-ephedrine and one (+)-norephedrine residue, are in equilibrium in benzene with a half-life at 30 "C of 11.4 min. Arguments have been presented for assigning the absolute configuration shown in (74) to the pure isomer obtained on crystallization.

(74)

(73)

1,3,5-Oxazaphospholens.-Details have appeared of the trapping with dip~larophiles~~ and with isocyanides44 of the nitrile ylides formed on thermal decomposition of the phosphoranes (75). In the absence of dipolarophiles, the nitrile ylide (76) d i m e r i ~ e dto~ give ~ (73, probably as shown.

(75)

@ NH

\

F,C

CF, (77)

41

4s 44 46

A. Klaebe, J. F. Brazier, F. Mathis, and R. Wolf, Tetrahedron Letters, 1972,4367. R. Contreras, J. F. Brazier, A. Klaebe, and R. Wolf, Phosphorus, 1972, 2, 67. K. Burger and J. Fehn, Chem. Ber., 1972, 105, 3814. K. Burger, J. Fehn, and E. Muller, Chem. Ber., 1973, 106, 1. K. Burger, K. Einhellig, G. Suss, and A. Gieren, Angew. Chem. Internat. Edti., 1973, 12, 156.

47

Quinquecovalent Phosphorus Compounds

Miscel1aneous.-Further examples have appeared of the use of amidoximes 46s 47 and of acyl hydrazides4*in the preparation of spirophosphoranes. The catechol liberated in the reactions of amidoximes with the cyclic phosphoramidite (78; X = Me,N) leads to the formation of stable six-co-ordinate species (see p. 49). In the proton n.m.r. spectrum of (79; R=Ph) at room

H

+ RIC(:NOH)NH,

1

RsC(:NOH)NHI

H

H

ZPNMe,

+ RCONHNH.2

-

H H

' l o 'ilR N" H

temperature, the methyl groups show three signals in the ratio 2 : 1 : 1, which separate into four equal signals in the presence of the shift reagent Eu(fod)3. Four different methyl absorptions would result if pseudorotations which place the five-membered rings diequatorial were, as expected, slow on the n.m.r. timescale. However, the proton n.m.r. spectrum of (79; R=Me) shows only two signals in the methyl region (apart from the hydrazide methyl) even in the presence of shift reagent. L. Lopez, M.-T. Boisdon, and J. Barrans, Compt. rend., 1972,275, C, 295. L. Lopez and J. Barrans, Compt. rend., 1973,276, C, 1211. R. Wolf, M. Sanchez, D. Houalla. and A. SchmidDeter. C o m t . rend.. 1972.275. C, 151.

48

Organophosphorus Chemistry

Amidrazones (80) also 4g give spirophosphoranes with trisdimethylaminophosphine or with cyclic phosphoramidites, e.g. (81).

RC(:NH)NHNH,.

+

MeCN

(MeaN),P

(80)

HHH

NIN 2

R r \p/ R N"/ \ N " N H H

The bis(trimethylsily1) thioether (82) with fluorophosphoranes gave lo the monocyclic phosphoranes (83), except with tetrafluorophosphoranes which gave the spirophosphoranes (84) and PF5, from which the salt (85) was obtained.

+

RnPF5-

PF6 and the sulphur di-imide (86) gave50 a small amount of a phosphorane,

S3N5PFS, to which the structure (87) has been assigned. The compound shows two different fluorine environments in its 19Fn.m.r. spectrum at 35 "C. This would not be expected for a molecule such as (87), in which a rapid pseudorotation to a topomeric trigonal bipyramid would lead to equivalence of the fluorines. Fragmentation of the intermediate phosphorane (88) has been proposed 61 to account for the deoxygenation of methyl p-tolyl sulphoxide by triphenylphosphine catalysed by tosyl isocyanate. 50

61

Y. Charbonnel and J. Barrans, Compt. rend., 1972, 274, C, 2209. H. W. Roesky and 0. Petersen, Angew. Chem. Internat. Edn., 1973,12,415. D. C. Garwood, M. R. Jones, and D. J. Cram, J. Ainer. Chem. SOC.,1973,95,1925.

49

Quinquecovalent Phosphorus Compounds F

PF,

+

I

- N\S=NTF //S=N,.,

Me3SiN=S=NSiMe, (86)

I

N\s4N

(87) 1-5%

ArSOMe

+ TsNCO + Ph,P

-+

,O\C=NT~ PhaP, 'S / \ Ar Me

0

(88)

Ar = p-MeC,H,

.1

Ph3P0

+ ArSMe + TsNCO

For the formation of quinquecovalent phosphoranes in the deoxygenation of nitro-olehs, see Chapter 10.

6 Six-membered Ring Following an investigation of the kinetics of the reduction of styrene ozonide with phosphitesYs2 the oxyphosphoranes (89) were proposed as intermediates in these reactions.

7 Six-co-ordinate Species A growing number of six-co-ordinate phosphorus-containing anions have been prepared. While these undoubtedly owe their stability partly to their spiro-nature, their very existence suggests that six-co-ordinate species may be much more important as reaction intermediates than has so far been recognized. The two by-products obtained from the reactions of amidoximes with the phosphoramidite (90) were also obtained46directly from (90) and catachol in acetonitrile. One (91) was the dimethylammonium salt of the known tris(ophenylenedioxy) phosphate anion; the other was formulated, on the basis of its 31Pchemical shift and PH bond, as the salt (92). This salt, on refluxing in 62

J. Carles and S. Flisziir, Canad.J , Chem., 1972, 50, 2552.

50

0rganophosphorus Chemistry

HO(92) 31P 99 p.p.m.

+

J(PH) = 800 Hz

1

51

Quinquecovalent Phosphorus Compounds

xylene, gave (91) and presumably hydrogen. The triethylammonium analogue (94) of (92) was subsequently in quantitative yield from the spirophosphorane (93) and catechol in the presence of triethylamine. Similar salts (95) were obtained from phenol and from alcohols, while with pyrrolidine the spirophosphorane (93) gave the salt (96). The amidoxime-derived spirophosphorane (97) with the aminoalcohol (98) gave4' the internal salt (99), which decomposed in polar solvents.

cyn PhCHz N H

+ HOCH2CMe2NH2 (981

0

I

(97)

CH2CMe2&H, (99)

Salts (101), similar to the above but containing carbon bonded directly to phosphorus, have been obtaineds4from the phosphonites (loo), catechol, and triethylamine in ether at room temperature. On heating they gave the phosphoranes (102), triethylamine, and hydrogen and were undoubtedly intermediates in previously reported reactions.66 A full account has appeared6sof the X-ray analysis of the salt (103).

(101)

31P

$113.5 p.p.m.

(R =

(103) 68 64 66

6a

Me)

(102)

R. Burgada, D. Bernard, and C. Laurenco, Compt. rend., 1973,276, C, 297. M. Wieber and K. Foroughi, Angew Chem. Internat. Edn., 1973, 12,419. M. Wieber and W. R. Hoos, Monatsh., 1970.101, 776. H. R. Allcock and E. C. Bissell. J. Amer. Chem. SOC.,1973,95,3154.

?

J

Halogenophosphines and Related Compounds BY J. A. MILLER

1 Halogenophosphines No major new developments have been reported this year, and the quantity and content of the literature is very similar to last year. Since publication in the field of Group IV phosphines has dropped this year, the chemistry of these compounds has been included in this section. Two reviews of phosphorushalogen compounds have appeared.’,

Physical Aspects.-& initio calculations on phosphorus trifluoride3 and difluoropho~phine~ have appeared, and the results compared3 with data from photoelectron spectra. An electron diffraction study has been made of the silylphosphines(l), and the Si-P bond length found to decrease slightly in the sequence n = 0 > n = 1 > YE = 2, while the C-P-Si bond angles are consistently 100k 1 o.6 The related silylamines(2) show relatively large changes in Si-N-C bond angle and in basicity, over the series n = 3 to n = 0, and the authors relate these contrasts to differences in bonding between nitrogen and phosphorus.6

Cyanodifluorophosphine (3) has a shortened C-P bond, and the P-C-N atoms are not collinear, as deduced from microwave studies.6 Infrared and Raman spectra have been reported for chlorodi-t-butylphosphine(4a) and fluorodi-t-butylphosphine (4b)’, and for difluoroiodophosphine (5a).8 and of Photoelectron spectra of a series of difluorophosphines (5b)--(5d),Q H. A. Klein and H. P. Latscha, Chem.-Ztg., 1973, 97, 77. R. H. Tomlinson, in Mellor’s ‘Comprehensive Treatise on Inorganic and Theoretical Chemistry’, Longmans, London, 1971, vol. 111, suppl. 111, pp. 438-535. L. J. Aarons, M. F. Guest, M. B. Hall, and I. H. Hillier, J.C.S. Faraday IZ, 1973, 69, 643. I. Absar and J. K. Van Wazer, J. Amer. Chem. SOC.,1972,94,6294. C . Glidewell, P. M. Pinder, A. G. Robiette, and G. M. Sheldrick, J.C.S. Dalton, 1972, 1402. P. L. Lee,K. Cohn, and R. H. Schwendeman, Znorg. Chem., 1972,11, 1917. ’ R. R. Holmes, G. T. K. Fey, and R. H. Larkin, Spectrochim. Acta, 1973 29A, 665. C . R. S. Dean, A. Finch, and P. N. Gates, J.C.S. Dalton, 1972, 1384. S . Cradock and D. W. H. Rankin, J.C.S. Faraday ZI, 1972, 68, 940.

52

53

Halogenophosphines and Related Compounds

the silyl derivatives (6) and (7),1° have been determined. In the latter paperlo the spectra are related to thermodynamic properties, such as basicity, by assignment of the low ionization potential band to the phosphorus lone pair. F,PCN

F,PR

(But),PX

(5) a ; R = I b; R = halogen C ; R = NH, d; R .= pseudohalogen e; R = NHSiH, f; R = Br

(4) a ; X = C1 b;X=F

(3)

.(H3Si)3M (6) M = N, P, or As

H2PSiH3

g;

(7)

R

= C1

The n.q.r. spectra of a series of dichlorophosphines(8) have been described.ll The following halogenophosphines have been subject to detail n.m.r. studies : dichloro(t-buty1)phosphine (9) [lineshape analysis and 3J(PCCH) values],le difluorophosphines (5c) and (5e) (double-resonance studies and sign of .I),'* and the borane complex (10) of tetrafluorodiphosphine (temperature dependence).l* RPCl (8)

R = CI, Ph, CH,Ph, or Me

ButPCl a

FzPPFs,BH,

(9)

(10)

Reactions.-The selection of the contents for the subdivisions of this section is not always clear cut, sometimes being based on mechanistic assumptions (made either by the original author or by the present Reporter), with which the reader may or may not agree. This is especially true of the reactions classified as biphilic. Electrophilic Attack by Phosphorus. Two standard reactions of acetylide reagents with halogenophosphines have been published. The first was used in preparation of difluoro(prop-1-yny1)phosphine (1 l), which was then converted into a phosphorane (see Halogenophosphorane section).ls Similar displacement of both chlorines from dichloro(t-buty1)phosphine (9) gave 75 % of the tertiary phosphine (12), from which the phosphabenzene (13) was prepared.le S. Cradock, E. A. V. Ebsworth, W. J. Savage, and R. A. Whiteford, J.C.S. Faraday 11, 1972, 68, 934. l1 P. Biryukov, K. V. Nikoronov, E. A. Gurylev, and A. Y . Deich, Zhur. obshchei Khim., 1972,42, 1223. J. B. Robert and J. D. Roberts, J. Amer. Chem. SOC.,1972, 94, 4902. l a D. W. W. Anderson, J. E. Bentham, and D. W. H. Rankin, J.C.S. Dalton, 1973, 1215. H. L. Hodges and R. W. Rudolf, Inorg. Chem., 1972.11, 2845. l * E. L. Lines and L. F. Centofanti, Znorg. Chem., 1973, 12, 598. G . Mark1 and D. Matthes, Angew. Chem. Internat. Edn., 1972, 11, 1019. lo

C

Organophosphorus Chemistry

54 F,PBr

+

LiCECMe + F,PC-CMe

(50 ButClz

+ PhC=CMgBr

--+

(1 1) Bu'P(C=CPh),

(9)

(12)

t

(1 3)

1 -Cyclopentadienyldifluorophosphine(1 4)has been prepared and suggested to be a fluxional molecule at temperatures above 25 OC.17 The principal evidence for this comes from n.m.r. studies, which reveal that above 25 "Cthe fluorines show coupling to five equivalent lH nuclei, and the J(FH) value falls from 11.5 to 2.5 H2.l'

A number of ligand-exchange reactions with Groups IV and VI compounds have been described this year. An extensive study of exchange between the difluorophosphines (5f) and (5g) and various silyl and germyl derivatives (15) was undertaken in order to examine the hypothesis that electronegative ligands prefer (in the thermodynamic sense) bonding to silicon rather than to germanium.lS The reactions of (5g) were difficult to interpret, but those of (5f) were generally consistent with theory, e.g. excess bromodifluorophosphine (5f) exchanged with 65% of (15a), but not at all with (15b).ls Bis(trifluoromethy1)chlorophosphineexchangeschlorine to give the ester (16).19Phosphorus trichloride reacts with (17) to exchange all the chlorines, although there are redox side reactions.20 2F,PBr + (H,M)20 BrMH3 -t (FJ')@ (5f)

(CFMCI

+ .(Me,Si),S

CF,N=SF,

-

(15) a; M = Si b; M = Ge

+ PCI:,

_cf

(CF&PSSiMe3 (1 6)

CF,N=SCI,

+ Me,SiCl + PF3

(1 7) J. E. Bentham, E. A. V. Ebsworth, H. Moretto, and D. W. H. Rankin, Angew. Chem. Internat. Edn., 1972, 11, 640. D. E. J. Arnold, J. S. Dryburgh, E. A. V. Ebsworth, and D. W. M. Rankin, J.C.S. Dalton, 1972, 2518. K. Gosling and J. L. Miller, lnorg. Nuclear Chem. Letters, 1973, 9, 355. M. D. Vorobiev. A. S. Filatov, and M. A. Englin, Zhur. obshchei Khim., 1972, 42, 1942.

55

Halogenophosphines and Related Compounds

The reactions of aryl amines with phosphorus trichloride are complex, and are a matter of some controversy.21sa2 A careful study of the reactions with excess phosphorus trichloride has shown that the main pathway involves two stages, and ultimate formation of the 2 : 2 adduct (18).23Phosphorus trifluoride reacts with NN'-dimethylethylenediamine to give the cyclic phosphine (19).24The formation and hydrolysis of the complex of phosphorus trichloride (and oxychloride) with pyridine have been studied.2S ArNH,

+ PC13

250c:

100

ArN(PC19 ) 2

* 20 "C

ArN-PCI

1

1

CIP -NAr

-

N H Me +PF, NHMe

(18)

Me "\F

ld Me

Difluorophosphine a i d e (20) has been prepared from either (5a) or (5f),26927 but there seems to be some disagreement in detail about its stability. Phosphorous acid fluorides (21) result from the hydrolysis of dihalogenophosphines in the presence of hydrogen fluoride.28The products of reactions between phosphorus trichloride and tertiary arsine sulphides are dependent upon the substituents on the ~ u l p h i d eFor . ~ ~example, triphenylarsine sulphide (22) simply desulphurizes, whereas dialkyl analogues (23) are converted into arsoranes.2s F,PX

+

( 5 ) a;

N3- -+

x

F,PN, (20)

= I

f ; X = Br 0

RPCIt

+

HF

+ HzO

R,PhAs(S)

+ PC13

(23) Ph,As(S)

+ PCI,

-

--+

II

RPHF

(21) RJ'hAsCI,

Ph3As

+

+

2HC1 [PSI

+ CI,P(S)

(22) H.-J. Vetter and H. Noth, Chem. Ber., 1963, 96, 1308. * a S. Goldschmidt and H.-L. Krauss, Annalen, 1955,595, 193. ** A. R. Davies, A. T. Bronsfield, R. N. Haszeldine, and D. R. Taylor, J.C.S. Perkin 1, 21

1973, 379. I4

I6

8B

S. Fleming, M. K. Lupton, and K. Jekot, Inorg. Chem., 1972, 11, 2534. R. G. Makitra, M. S. Makaruk, and M. N. Didych, Zhur. obshchei Khim., 197242,1877. E. L. Lines and L. F. Centofanti, Inorg. Chem., 1972,11,2269. S . R. O'Neill and J. M. Shreeve, Inorg. Chem., 1972, 11, 1629. U. Ahrens and H. Falius, Chem. Ber., 1972, 105, 3317. G. M. Usacheva and G. Kh. Kamai, Zhur. obshchei Khim., 1971,41,2705.

56

Organophosphorus Chemistry

Nucleophilic Attack by Phosphorus. The reaction of halogenophosphines with alkyl halides, in the presence of Lewis acids, has been a most useful source of a variety of organophosphorus halides.30A study of the intermediate complex in the reaction of t-butyl chloride with dichloro(methy1)phosphine (24) has confirmed31that it is a 1 : 1 complex, as originally

+ AICI,

BdCl

3- MePCI, -+

[ButMePCI,]~~AICI,-

(24)

Trimethylsilyldiphenylphosphine(25) reacts with aromatic acid chlorides to produce aroyldiphenylphosphines,which are generally not very stable to the reaction conditions32- see Phosphine Oxide chapter. French workers have made further studies of the insertion reactions of silyl- and germylphosphines with carbonyl compounds. Glyoxal is converted into the phosphines (26) and (27),33while keten gives the phosphine (28)34 with Group IV phosphines. 0

Me,,SiPPh,

II + ArCCl

0 d

Me,SiCl

+

I1

ArCPPh,

(25)

PEt,

I

R,MOCHCH=O (26) M = Si or Ge

CH=O

I

.CH2=C=0

+ RjSiPEt,

-

R,SiOC

/

PEt,

\CH, (28)

Biphilic Reactions. The mechanistic complexities of the reactions of halogenophosphines with ambident electrophilic carbonyl compounds are well illustrated by the problem of the reaction of dichlorophosphines (29) with acrylic acid, to produce the tertiary phosphine oxides (30). Two suggestions in the literature have involved an initial nucleophilic phosphorus reaction, I*

*'

'* 14

A. M. Kinnear and E. A. Perren, J . Chem. SOC.,1952, 3437. J. I. Bullock, N. J. Taylor, and F. W. Parrett, J.C.S. Dalton, 1972, 1843. H. Kunzek, M. Braun, E. Nesener, and K. Ruhlmann, J. Organometallic Chem.. 1973, 49, 149. C. Couret, J. SatgC and F. Couret, Inorg. Chem., 1972, 11, 2274. C. Couret, J. Satgt and F. Couret, J. Organometallic Chem., 1973, 47, 67.

57

Halogenophosphines and Related Compounds

or at the acidic However, the either at the @-carbonof the carbonyl oxygen has been suggested to displace halogen from electrophilic phosphorus in the first step.37The electrophilic phosphorus suggestionappears to have been eliminated by the results of competitive reactions for acrylic acid between the phosphines (29; R=Et) and (29; R=Ph), from which the latter was recovered unchanged (85 %).38 Moreover, in reactions of (29; R = Et) with a mixture of acrylic and methacrylic acids, the latter failed to compete.88 Assuming that the reaction pathway does not vary with the phosphine used, and that the first stage is rate-determining, the schemes outlined [for (29; R=Et)] are compatible with the new results.

RPCI,

+ CH,=CHC02H

CI

Nucleophilic P

I+ I

Et PCH,CH=C

H EtTCl, OCCH=CH,

I1

0

OH

CI

Nucleophilic P at acidic H

/O\

I JEt\+ 0 c1, p z o

Cl-

c1 0

I II

EtPOCCH=CH2

+ HCI

0

II

0

It

EtPCH ZCHZCCI I

The reactions of halogenophosphines with aldehydes to yield ct-halogenoalkylphosphoryl compounds present similar difficulties in mechanism. In the reactions of phosphorus trihalides with a range of aldehydes, bis-cc-halogenoalkyl ethers (31) and gem-dihalides (32) have been shown to be successive intermediates leading to the phosphonyl dihalides (33).39The known formation of (31) or (32) from the reactions of aldehydes with electrophilic halides like boron trichloride or thionyl chloride suggests a similar role for the phosphorus trihalides, and the relative rates of the reactions of phosphorus trichloride with p-substituted benzaldehydes have confirmed this ~uggestion.~~ 8b

ao 37 3B

3g

V. K. Khairullin and R. R. Shagidullin, Zhur. obshchei Khim, 1966,36, 289. T. Kh. Gazizov, M. A. Vasyanina, A. P. Pashinkin, N. P. Anoshina, E. I. Gol'dfarb, and A. N. Pudovik, Zhur. obshchei Khim., 1971, 41, 1857. V. S. Tsivunin and N. I. D'Yakonova, Zhiir. obshchei Khim., 1970, 40, 1995. T. Kh. Gazizov, A. P. Pashinkin, G. V. Dmitrieva, L. L. Tuzova, V. K. Khairullin, and A. N. Pudovik, Zhur. obshchei Khim., 1972, 42, 1730. J. A. Miller and M. J. Nunn, Tetrahedrotz Letters, 1972, 3953.

58

RCH=O 4 PX,

--

(RCHXj20

0 RCHX~~X, (33)

Orgarlophosphorus Chemistry

(3 1)

RCHX~ (3 2)

Aryldichlorophosphines react with carboxylic acid acylals to give phosphinic chlorides (34), although no evidence for mechanism has been OEt

ArPCI,

0

I II + MeCHOCOMe + ArPCH(0EtjMe + I

MeCOCl

c1 (3 4)

A detailed investigation of the reaction between tetraiododiphosphine (35) and benzyl chloride (Scheme 1) has enabled the authors to explain the formation of phosphorus trichloride and of polybenzylated phosphorus compounds, after hydroly~is.~~

312PC1

=i= 2PI, +

+ PCIs (PhCHz)zPI2CI

0 PhC€i,C{

H20''*

II

(PhCH,),POH

(PhCH,),fPCI TzCl

1 H,O

f

(PhCH,),P= 0

Scheme 1

Phosphorus tri-iodide is formed in an equilibrium with tetraiododiphosphine P-P bond(35) when the latter is treated with organic ~ u l p h i d e sFurther .~~ 40

41

4a

M. B. Gazizov, D. B. Sultanova, A. I. Razumov, G. N . El'Nikova, and L. P. Ostamina, Zhur. obshchei Khim., 1972, 42, 21 12. L. P. Zhuravleva, and M. I. Z'Ola, Zhur. obshchei Khim., 1972,42, 526. N . G. Feshchenko, Zh. K. Gorbatenko, and T. V. Kovaleva, Zhur. obshchei Khim., 1972, 42, 284.

Halogenophosphines and Related Conzpormds

59

forming and -breaking reactions of amines and of elemental sulphur have also been Cyclic phosphine oxides (36) result from the reaction of a, w-di-iodides with the di-iododiphosphine (37).4'*

(38) X = halogen

Treatment of hexafluoroacetone with halogenophosphines yields 1,3,2dioxapho~pholans,~~ presumably of the general type (38) - details not available. Oxidations of phosphorus trifluoride with oxygen, sulphur, or selenium,46 and of phosphorus tri-iodide and (35) with selenium, 47 have been reported see Phosphine Oxide chapter. Miscellaneous Reactions. Phosphorus trichloride and aluminium chloride ring-open the silacyclobutane (39) to give the phosphonous dichloride (40).48 The equilibrium reaction leading to the mixed diphosphine-p-oxide (41)lies well to the right,49in accordance with the n-acceptor theory of such exchanges.60

(39)

(('F,),POP(CF:,)2

+

F,PC)PF,

(CF,),POPF, (41)

44

46

'' '* Ls

N. G. Feshchenko, T. V. Kovaleva, and A. V. Kirsanov, Zhur. obshchei Khim., 1972, 42, 287. N. Ya Derkach, I. M. Kononenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1971, 41, 2806. V. N. Volkovitskii, I. L. Kununyants, and E. G. Bykhovskaya, Zhur. Vsesoyuz. Khim. obshch. im. D.I. Mendeleeva, 1973, 18, 112. A. P. Hagen and E. A. Elphingstone, Znorg. Chem., 1973, 12, 478. M. Baudler, B. Volland, and H.-W. Valpertz, Chem. Ber., 1973, 106, 1049. E. F. Bugerenko, A. S. Petukhova, and E. A. Chernyshev, Zhur. obshchei Khim., 1972, 42, 168. R. G. Cave11 and A. R. Sanger, Znorg. Nuclear Chem. Letters, 1973, 9,461. A. B. Burg and J. S. Basi, J . Amer. Chem. SOC.,1963, 90, 3361.

60

Organophosphorus Chemistry

Phosphorus trifluoride reacts with the nitroxide radical (42) as shown.61 The effect of FeIII and CuI or CuII additives, and of solvent, on the formation of (43) by y-irradiation of cyclohexene in the presence of phosphorus triN-Silylaminodifluorophosphine (44) has been chloride has been prepared from (5c) and its n.m.r. spectrum

+

(CF,),N6

PF,

-

(CF,),NOPF,

(42)

H,,SiBr

+

(43) H,SiNHPF,

H,NPF,

(44)

(5c)

2 Halogenophosphoranes Structure and Bonding.-The question of 4s and/or 4p orbital participation in bonding in phosphoranes has been investigated in a series of calculations based on phosphorus pentafl~oride.~~ It appears that the promotion energy to the 4s orbital is greater than that for the 3d orbital, and the author concludes that the former are not likely to be important in bonding.54 Two years ago it was suggested66that the temperature dependence of the n.m.r. of the phosphorane (45a) could not be rationalized in terms of Berry pseudorotation (BPR), and that an intermolecular route might be operating. This matter has been re-examined for the phosphorane (45b), and temperature and solvent dependence of its n.m.r. spectrum found to be compatible with a BPR process.68The suggest that the original work56may have been complicated by the presence of hydrogen fluoride, formed via the glass n.m.r. cells. In a more theoretical approach to the same problem, arguments have been made for the intermolecular pathway, via octahedral intermediate^.^' RrPF, (45)

a;

b; c;

R R R

= Me = Ph = NH,

C. S.-C. Wang and J. M. Shreeve, Inorg. Chem., 1973, 12, 81. E. I. Babkina and I. V. Vereshchinskii, Zhur. obshchei Khim., 1972, 42, 1285. s3 D. E. J. Arnold, E. A. V. Ebsowrth, H. F. Jessep, and D. W. H. Rankin, J.C.S. Dalton, 1972, 1681. 6 4 R. G. A. R. Maclagan, J.C.S. Faraday 11, 1972, 68, 1 1 17. l 6 T. A. Furtsch, D. SDierdorf, and A. H. Cowley, J. Amer. Chem. SOC., 1970, 92, 5759. I* C. G. Moreland, G . 0. Doak, and L. B. Littlefield, J . Amer. Chem. SOC.,1973, 95,255. 6 7 J. 1. Musher, Tetrahedron Letters, 1973, 1093.

Halogenophosphines and Re Iated Compounds

61

Further support has appeared for the view5* that x-donors prefer an equatorial site in a trigonal bipyramid, and that, when so placed, the donor will have its donor orbital in the equatorial plane. Thus the n.m.r. of the phosphorane (4%) indicates that the hydrogens are axially oriented, and coupled strongly to the axial fluorines [as in structure (46)69].

(46)

Phosphorus pentachloride (47) has received an unusually high share of attention over the past year. A long overdue study of the effect of solvents on the various equilibria involving (47) and ionic species has appeared.60From laser Raman spectra, and freezing point depression data, it has been shown that, in polar solvents, (47) is ionizing in two different ways, and that the two equilibria are largely dependent upon concentration of (47). In benzene, (47) is monomeric, and the alleged dimer in carbon tetrachloride appears to be non-existent and incorrectly characterized because of solid-solution formation.6O F a g

-

k14

predominant at >0.03 mol 1-

PCI:, -

predominant at 10.03 mol I-' 4

6CI4 El

(47)

A study has been made of the reversible association between (47) and solvents containing carbonyl or ether functions.61Other reports have appeared on the dissociation and stability of (47),62its Raman spectrum in anhydrous hydrochloric its n.q.r. and on the heat capacity of (47).66 The X-ray photoelectron spectrum of phosphorus pentafluoride confirms the trigonal-bipyramidal structure and the relatively longer axial P-F bonds.66An electron diffraction study of the fluorophosphorane (48) has been made.67 Me,PF,

(48) rD .SO

a

'* Oa

Oa

R. Hoffmann, J. M. Howell, and E. L. Muetterties,J. Amer. Chem. SOC.,1972,94,3047. E. L. Muetterties, P. Meakin, and R. Hoffmann, J . Amer. Chem. SOC.,1972,94,5674. R. W. Suter, H. C. Knachel, V. P. Petro, J. H. Howatson, and S. G . Shore, J. Amer. Chem. SOC.,1973,95, 1474. V. G. Rozinov, V. V. Rybkina, and E. F. Grechkin, Zhur. obshchei Khim., 1972, 42, 1167. L. D. Polyachenok and 0. G. Polyachenok, Zhur. $2. Khim., l973,47,498B. P. V. Huong and B. Desbat, Bull. SOC.chim. France, 1972, 2631. H. Chinara and N . Nakamura, Bull. Chem. SOC.Japan, 1973, 46, 94. H. Chihara, M. Nakamura, and K. Masukane, Bull. Chem. SOC.Japan, 1973, 46, 97. R. W. Shaw, T. X. Carroll, and T. D. Thomas, J. Amer. Chem. SOC.,1973, 95,2033. H. Yow and L. S. Bartell, J. Mol. Structure, 1973, 15, 209.

62

Organophosphorus Chemistry

Preparation.-Details have appeared of the preparation of tetra-alkylfluorophosphoranes (49) from ylides, and of the structures of the phosphoranes.68 The related addition of methanol to methylene ylides yields tetra-alkylalkoxyphosphoranes (50),69which are unusual in that one alkyl group is axial in the trigonal-bipyramidal structure. These decompose thermally, but the pathway depends on the substituents. R,P=CH,

M e 0 !I

d R,MeP(OMk)

(50)

R =Me

Me,P=O

R = Ph

McPPh,

+ CzHs

RR,MePF (49)

+

McOPh

Prop-l-ynyltetrafluorophosphorane (5 1) has been prepared from the corresponding ph0~phine.l~ The fluorophosphoranes(45b) and (52) have been prepared using molybdenum hexafl~oride.~~ Phosphorus trichloride converts dialkyl(pheny1)arsine sulphides into the corresponding dichloroarsorane

(53).29 F,PC-CMe

+

SbF,

SbC'3+

F,PCfCMe

(51) Ph,PCl

+

MoF, -+ Ph,PF,

(45b)

Silicon-exchange routes to phosphoranes are being increasingly used in preparative phosphorane work. For example, tetrafluorophosphorane (54) has been synthesized by an improved route via trimethyl~ilane,~~ and its n.m.r. spectrum analysed for a trigonal-bipyramidalstructure with axial f l u o r i n e ~ . ~ ~ The fluorophosphorane (55) can be prepared from N-trimethylsilyl-2-methylp y r r ~ l e and , ~ ~ the n.m.r. spectrum (non-equivalent axial fluorines) appears to conform to the z-donor theories advanced a year

q1

H. Schmidbaur, K.-H. Mitschke, W. Buchner, H. Stiihler, and J. Weidlein, Chem. Ber., 1973, 106, 1226. H. Schmidbaur, H. Stiihler, and W. Buchner, Chem. Ber. 1973, 106, 1233. F. Mathey and J. Bensoam, Compt. rend., 1972, 274, C, 1095. A. H. Cowley and R. W. Braun, Znorg. Chent., 1973, 12, 491. M. J. C. Henson, R. Schmutzler, and W. S. Sheldrick, J.C.S. Chem. Comm., 1973, 190.

Hulogenophosphines and Related Compounds Me,SiI-E

+ PF,

63

+ F,PH

Me,SiF

(54)

A number of alkoxy and related fluorophosphoranes have been prepared by the routes indicated. The alkoxyphosphoranes (56)73 and (57)74are stable only when substituted as shown. The phosphorane (58) has a structure intermediate between a trigonal bipyramid and a square pyramid.75 Me,SiOR2 3. R'PF,

tEpp.fR1PF30R2 R1 = Me or Ph

(56)

R,P(X)Y

+

(Me,Si),O

=

'*

R ,P(Y)(OSiMed 2 (57) stable when

I

R = Y = C F 3

R,P(O)OSiMc, , ,*SSiMe3

'SSiMe,

L"

Reactions.-The cis-addition of phosphorus pentachloride to acetylenes has been confirmed, although the reactions are not always clean, as shown by the additions to propyne (59) and but-l-yne (60),in which the additional products appear to result from reaction of hydrogen chloride with the initial a d d u ~ t . ' ~ 75

74

76 76

D. U. Robert, G. N. Flatau, C. Demay, and J. G. Reiss, J.C.S. Chem. Comm., 1972, 1127. R. G. Cavell, R. D. Leary, and A. J. Tomlinson, Znorg. Chem., 1972, 11, 2578. M. Eisenhut, R. Schmutzler, and W. S. Sheldrick, J.C.S. Chem. Comm., 1973, 144.

A. V. Dogadina, K. S. Mingaleva, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1972,42,2186.

Organophosphorus Chemistry

64

i 3-

0

I1

McCFI= CC1C H 21' C:1

The en-yne (61) reacts with phosphorus pentachloride to give the adduct (62). 77 Styrene and phosphorus pentachloride react to give distyryltrichloroto form the phosphinic phosphorane (63), which has now been chloride (64), and not the corresponding phosphinous ~hloride,'~ on treatment with methyl phosphorodichloridite.

Details of the reaction between phosphorus pentachloride and acetals of or-keto-acids include mechanistic studies. The intermediate oc-chloroaceta1 (65) is formed almost instantaneously at below 0 "C, and CO and HCl simultaneously evolved.goStereochemical studies of the acetal ring-opening indicate that this step involves inversion. The suggested mechanismgois consistent with the original observation that alkaline hydrolysis of the B-chloroacetate (66) gives an epoxide with the same absolute stereochemistry as the diol from which the original acetal was derived.

7'

ao

A. V. Dogadina, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 1919. V. S. Galeev, Ya. A. Levin, Zhur. obshchei Khirn., 1972, 42, 1496. Y.A. Levin, V. S. Galeev and N. V. Evdokimova, Byul. Izohret., 1969, no. 2. M. S. Newman and C. H. Chen, J. Org. Chem., 1973,38, 1173.

Halogenophosphines and Related Compounds

65

0

LO

+ C1- +

II

MeCO\6H

The cleavage of 1,3-dioxolans (67a) by phosphorus pentachloride has been claimeds1 to involve 2-chlorodioxolan intermediates [cf. (66), above]. The products are normally vinylphosphonic dichlorides (68) and their formatione2 from 2,2-dimethyl-l,3-dioxolan(67b) suggests that another route is more likely - as ref. 82 would also indicate. 2-Ethyl-l,3-dioxolan (67c) yields the dichloride (69).8s 0

II

ClCH,CH,OCH=C

/ \

PCl * (69)

Me

For (67Qt

(67)a; R1 = H; R2 = H or alkyl b; R1 = R2 = Me C; R' = H ; R 2 = Et

CI(CH,),OC(Me)= CHPCII (68)

The bisperoxide (70) reacts with phosphorus pentachloride to yield the vinylphosphonic dichloride (71).84 Santonin (72) chlorinates in stages on treatment with phosphorus pentachloride or thionyl chloride.86

86

K. A. Petrov, M. A. Raksha, and V. L. Vinogradov, Zhur. obshchei Khim., 1966, 36, 7151. S. V. Fridland, S. K. Chirkunova, and T. V. Zykova, Zhur. obshchei Khim., 1972, 42, 117. S. V. Fridland, L. K. Dalmatova, and S. K. Chirkunova, Zhur. obshchei Khim., 1972, 42, 1916. A. I. Shreibert, F. V. Mudryi, L. M. Mudraya, and A. K. Brel, Zhur. obshchei Khim., 1972,42, 1867. A. Frohlich, K. Ishikawa, and T. B. H. McMurry, Tetrahedron Letters, 1973, 995.

66

Organophosphorus Chemistry 0

(Bu'OO),CHMe

II

+ PCI,

-% ButOOCH=CHPCI, (71)

(70)

A comparison has been made between the reactions of pyridine N-oxide (73) and nitrosobenzenes (74) with phosphorus pentachloride.86 Neither reaction is clean, but the N-oxide tends to deoxygenate, whereas (74) is halogenated predominantly in the para-position by an unidentified species.ss

1

(mainly)

-0 (73)

o

N

=

O PCI,

(74)

*

n

N

=

O

+ others

c1 (mainly)

Phosphorus pentachloride with hydrogen chloride has been found to be efficient in the cyclization of benzonitrile to the sym-triazine (75).87 Adipic acid diamide (76) reacts with phosphorus pentachloride as shown.ss The reaction of sulphur tetrafluoride with phosphorus pentachloride yields a salt-like product, formulated as (77) or (7Qs9 ** R. C. Duty and G. Lyons, J. Org. Chem., 1972,37,4119. S. Yanagida, M. Yokoe, M. Ohoka, and S. Komori, Bull. Chem. SOC.Japan, 1973, 46, 306.

H. A. Klein and H. P. Latscha, Z . anorg. Chem., 1973,396,261. L. N. Markovskii, E. A. Stukalo, and A. V. Kirsanov, Zhur. obshchei Khim., 1972,42, 2581.

Halogenophosphines and Related Compounds

67

Ph I

PCI,-HCI

PhCSN

x;l

Ph

Ph

(75)

(76)

2PC15

+

+ [C13F6PS] (?) either (77) kF68a,

3SF4

SCI4

or (78) C1,SF SF,

Trifluoroacetamide reacts with phenyltetrafluorophosphorane to give (79).g0The same phosphorane reacts with diphosphine disulphides, but only the disulphide (80) gave one pair of products.B1The N-trirnethylsilylirnide derivatives (81),92 (82),92 and (83) 93 react as indicated with phosphorus

pentafluoride. 0 PhPF,

+

0

II

CF3CNH2

II

__f

PhPF2=NCCF3 (79)

S

PhPF,

l p ,

+ RP,

II

b*

es

+

II

,PR

PhPF2

S

0

Me,S=NSiMe3

II

PF,

-

qs 'S

S

S

+

I

.F

a

PF,

G. Gzieslik and 0. Glemser, 2.anorg. Chem., 1972, 394, 26. R. K. Harris, J. R. Woplin. M. Murray, and R. Schmutzler, J.C.S. Dalton, 1972, 1590. R. Appel, I. Ruppert, and F. Knoll, Chem. Ber., 1972,105,2492. H. W. Roesky and 0. Petersen, Angew. Chem. Internat. Edn., 1973, 12,415.

68

Organophosphorus Chemistry

The reactions of dihalogenophosphoranes, or their chemical equivalent, continue to be exploited in general organic synthesis. Dibromotriphenylphosphorane (84) deoxygenates the ether (85), and the resulting dibromide is readily a r o m a t i ~ e d Benzoins .~~ may be oxidized to benzils by (84).96

0

II

ArCCH(0H)Ar

+ Ph,PBr,

-

00

II II

ArCCAr 3- Ph3P 2HBr

+

wMe mMe (84)

+ Ph3PBr,

+ Ph3P=0

_j

Me

Me

(84)

(85)

Br

rilicap

Epoxides are converted into cis-1,Zdihalides by refluxing with a solution of triphenylphosphine in carbon tetrachloride or tetrabr~mide.~~ The reaction involves inversion at both epoxide carbon atoms, and a reasonable rationale is outlined for cyclohexane epoxide (86) in carbon tetrachloride.

0 0

+ Ph3$CCI, C1-

1 CC13

1

'' J. DeWit and H. Wynberg, Rec. Trav. chim.,1973, 92,281. *' T.-L. Ho, Synthesis, 1972, 697. "

N. S. Isaacs and D. Kirkpatrick, Tetrahedron Letters, 1972, 3869.

69

Halogenophoshines and Related Compounds

The 2-chlorination of 1,3-distearoylglyceroI (87) by triphenylphosphine in carbon tetrachloride proceeds stereospecifically, again with inversion.s7 An extensive investigation of the reaction of triphenylphosphine in carbon tetrahalide-dimethylformamide with nucleoside hydroxy-functions has been published.98 Tris-NN-dimethylaminophosphine in carbon tetrachloride converts methyl a-O-glucopyranoside (88) quantitatively into an isolable alkoxyphosphonium salt.BB CHzOR CHOH I

I

CHzOR PhsP-CCId

*

I I

Cl--CH

CH2OR

CHzOR

(87) R = stearoyl C1- +P(NMe&

HQ

+ (Me,N),P HOQMe OH

w

-

I

0

CCId

HO QMe OH

R. Aneja, A. P. Davies, and J. A. Knaggs, J.C.S. Chem. Comm., 1973,110. J. P. H. Verheyden and J. G. Moffatt, J. Org. Chem., 1972,37, 2289. B. Castro, Y. Chapleur, B. Gross, and C. Selve, Tetrahedron Letters, 1972, 5001.

4 Phosphine Oxides, Sulphides, and Selenides BY J. A. MILLER

1 Introduction

As no significant work on physical aspects of phosphine oxides has appeared over the current year, this section has been omitted. The chapter has been divided into sections on the preparation and on the reactions and pmperties of phosphine oxides, and comment made on spectra or other physical properties where appropriate.

2 Preparation From Secondary Phosphine Oxides or from Phosphinites.-Diphen ylphosphine oxide (l), as its magnesium ester, has been converted into tertiary phosphine oxides by reaction with carbonyl compounds1 such as acetone and crotonaldehyde. With ag-unsaturated ketones,l$ however, the preferred reaction is a 1,4-addition, as with the ketone (2), which yields the bis-oxide (3).l In the same paper,l details have appeared of the generation of the anion of diphenylphosphine oxide from benzyl diphenylphosphinylformate (4). Trapping of this anion by benzoyl chloride yielded diphenylphosphinylbenzyl diphenylphosphinate (3, probably produced via the highly reactive3benzoyldiphenylphosphine oxide (6). Another group4 has obtained the ester (5) from benzoyl chloride and trimethylsilyldiphenylphosphine(7) - see Halogenophosphines, Chapter 3. Further studies of the rearrangement of propargyl and related phosphinites to allenic phosphine oxides have been reported by French workers.sss The rearrangement is known' to be stereospecific, and this has been used to determine the stereochemistry of acetylenic alcohol^.^ The propargyl-ally1 alcohol (8) was found, as expected, to rearrange via the triple bond only.6 The P. F. Cann, S. G. Warren, and M. R. Williams, J.C.S. Perkin I , 1972, 2377. P. F. Cam, D. Howells, and S. G . Warren, J.C.S. Perkin 11, 1972, 304. a See J. A. Miller, in 'Organophosphorus Chemistry' ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1971, vol. 2, pp. 56-58. H. Kunzek, M. Braun, E. Nesener, and K. Ruhlmann, J. Organometallic Chem., 1973, 49, 149. D. Guillerm and M. L. Capmau, Tetrahedron, 1972, 28, 3559. M. Huche and P. Cresson, Tetrahedron Letters, 1972, 4933. ' A. Sevin and W. Chodkiewicz, Bull. SOC.chim. France, 1969, 4016.

70

Phosphine Oxides, Sulphides, and Selenides

71

0

0 0

0 Ph,POEt

+

I1

ClCOCH,Ph

-+

I1 II

Ph2P--COCHfPh

[ph2i]

+

C02 + ICH,Ph

+

Me3SiC1

0

II

Ph2PSiMe, 3- PhCOCl + PhCPPhs

(7)

I

H 2 0 [O]

Y (5)

bis(dipheny1phosphine) oxide (9) has been synthesized and an n.m.r. study made of its hindered rotation (by a variable-temperature method).* A re-examination of the reaction between p-benzoquinone and diphenylphosphine oxide (1) has confirmed the originallostructural assignment to the phosphine oxide product (10). The related reaction of chlorodiphenylphosphine yields p-hydroxyphenyl diphenylphosphinate (1 1). The authors were D. Howells and S. G. Warren, Tetrahedron Letters, 1973, 675. I. M. Magdeev, Y. A. Levin, and B. E. Ivanov, Zhur. obshchei Khim., 1972,42,2415. I. G . M. Campbell and I. D. R. Stevens, Chem. Comm., 1966, 505; J. Chem. SOC.(C), 1971, 1836.

72

Organophosphorus Chemistry

M e C f C C H ( 0 H)CH=C H Mc (8)

Me

CH=CHMe

f

Ph,PC&

.CH=CHMe

0

0

II

Ph ,P--?H-CMe

1

I1

,PPh 2

not able to rationalize the difference in reaction pathway, although there is close analogy in the reactions of tetracyclone (12), which gives conjugate addition products with the oxide (l), but is attacked at the carbonyl oxygen by tertiary phosphines.ll 0

il

PPh 2

Q Q qK 0 ’

@IPh2 OH

i, Ph,PCI ii, H,O

0

OH

Ph

Ph

0

By Grignard and Related Reactions.-1 -Phosphabicyclo[2,2,1Iheptane 1-oxide (13) has been synthesized12 by the route outlined, and detailed europium shift-reagent and 13C n.m.r. studies reported.13 These bridged oxides are See J. A. Miller in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, 1973, vol. 4, p. 77. l’ R. B. Wetzel and G. L. Kenyon, J . Amer. Chem. SOC.,1972,94,9230. l 8 R. B. Wetzel and G. L. Kenyon, J.C.S. Chem. Comm., 1973,237. l1

Phosphine Oxides, Sulphides and Selenides

73

characterized by exceptionally large values of 3J(PCCH) coupling constants, e.g. (13) has a value of 28 Hz (see Physical Methods, Chapter 11). A related cyclization of a dibromide has been used in the preparation1*of novel 1,2,3-triphenyIphosphiren 1-oxide (14), from bis(cc-bromobenzy1)phenylphosphine oxide (1 5), using DBN as a double dehydrobrominating agent. The three-membered ring may be cleaved thermally or by alkali. Vinylphosphine oxides (16) may have been synthesized l6 by Grignard reactions of bis(P-bromoethyl)phosphinyl chloride (17) in the presence of base.

PhC,CPh

0

0

II (BrCH2CH,),PCI

+ RMgX

(1 7)

EtsN

II

+ (CHZ=CH)ZPR (16)

By Oxidation of Phosphines.-Standard

oxidation procedures have been described for the formation of several unusual phosphine oxides, e.g. (18), and hence (19);16(20)17and (21);18(22),lgand (23).20

l4

E. W. Koos, J. P. V. Kool, E. E. Green, and J. K. Stille, J.C.S. Chem. Comm., 1972, 1085.

l6

lB

Y. A. Levin, R. I. Pyrkin, and M. M. Gilyazov, Zhur. obshchei Khim., 1972, 42, 1166. Y. Kashman and E. Benary, Tetrahedron, 1972, 28,4091. K. C. Srivastava and K. D. Berlin, f. Org. Chem., 1972,37,4487. F. Mathey, G. Muller, and H. Bonnard, Bull. SOC.chim. France, 1972, 4021. Z . N. Mironova, E. N. Tsvetkov, L. I. Petrovskaya, V. V. Negrebetskii, A. V. Nikolaev and M. I. Kabachnik, Zhur. obshchei Khim., 1972, 42, 2152. G. Mark1 and D. Matthes, Angew. Chem. Internat. Edn., 1972, 11, 1019.

74

oo v

Organophosphorus Chemistry

+ PhPHz

i, base

____f ii, HIOt

Ph-P

ll

i,BH;

.

ii, Pb(OAc)d

0

i, RZ2NHin

R'nP(CH2OAc) 3 - 8

aq. M~OH-KOH

ii, HzOI

F

11

R1,1P(CH,NR2,),-, (22) R1 = cycloalkyl

ButPCl,

+ PhCECMgBr

-+

ButP(CGCPh), 1HdL

0

II

ButP(C=CPh) (23)

Phosphine Oxides, Sulphides, and Selenides

75

Treatment of the bicyclic phosphine (24) with sulphur results in ring cleavage when Ar=p-MeOC,H,, but in no reaction when Ar=pOZNCeH,! 21 1,2,3-Benzotriphospholesreact with sulphur to produce either a monosulphide or a disulphide, and 31Pn.m.r. was used to assign the structures (25) and (26), respectively.22 ZH,OH

Ph

D t .

V

P

’ Ph

W

P

.S

’ Ph

1

A useful development in this year’s synthetic work on phosphine sulphides is the report of a one-step conversion of a phosphine oxide into the corresponding sulphide by treatment of the former with boron trisulphide.2s It appears that the conversion is highly stereospecific, and the phosphine sulphide product (27) has retained stereochemistry at phosphorus.

Two reports of phosphine selenide preparation from selenium have appeared. Trifluorophosphineselenide (28) is unstable but can be manipulated (mass spectrum given) in a vacuum line in the dark.24The corresponding OP

as 24

E. S. KOZIOV,A. I. Sedlov, and A. V. Kirsanov, Zhur. obshchei Khim., 1972, 42, 519. F. G. Mann and A. J. H. Mercer, J.C.S. Perkin I, 1972, 1631; B. E. Maryanoff, R. Tang, and K. Mislow, J.C.S. Chem. Comm., 1973, 273. A. P. Hagen and E. A. Elphingstone, Inorg. Chem., 1973,12,478.

76

Organophosphorus Chemistry

reactions of phosphorus tri-iodide or tetraiododiphosphine give isolable products, the selenides (29), (30), and (31).25

PF,

+ Se

in vacuo

F,PSe (28)

By Miscellaneous Routes.-Benzyne and pentaphenylphosphole 1-oxide (32) yield the bicyclic oxide (33), which on pyrolysis yields tetraphenylnaphtha1ene.26The other pyrolysis product, phenylphosphinidene oxide (34), was trapped by the reactions outlined below, although trapping with isoprene or acetylenes failed.26

J.

Ph

0

II

PhP(SEt)z 0

II

PhPOMe

I

OH

.

Et,S,

[PhP=O]

+

ph@ Ph

(34)

MeY

J

Ph

CB2=C(OEt),

0 II

(Et 0),PPh

Two rearrangements are described which lead to the phosphepin 1-oxide ( 3 9 , from the bicyclic phospholan 1-oxide (36), or the isomeric phosphepin 1-oxide (37).27 Phospholes have been shown to ring-expand to the oxides (38) on treatment with benzoyl chloride and alkali,28and the reaction found ID

1’

M. Baudler, B. Volland, and H.-W. Valpertz, Chem. Ber., 1973, 106, 1049. J. K. Stille, J. L. Eichelberger, J. Higgins, and M. E. Freeburger, J. Arner. Chem. Soc., 1972,94,4761. G. Mark1 and G. Dannhardt, Tetrahedron Letters, 1973, 1455. F. Mathey, Tetrahedron, 1972, 28, 4177.

Phosphine Oxides, Sulphides, and Selenides

77

to be general except for R = But, in which case the product is the phosphol-3ene 1-oxide (39).29 The rearrangement reaction has been rationalized as shown, and resembles other ring-expansion reactions of p h o s p h ~ l e s31. ~ ~ ~ AI,O, or

Et,N

>

Three papers have appeared on the synthesis and synthetic utility of halogenoalkylphosphine oxides, such as tris-(2-~hloroethyl)phosphineoxide (40) and bis-(2-chloroethyl)chloromethylphosphine oxide (41).32-34 A summary of these reactions is shown. Another reaction leading to a-halogenoalkylphosphineoxides (42) is that between aldehydes and halogenoph~sphines.~~ With phosphorus trihalides, the pathway to the oxides (42)has been shown to be quite complex, and, for simple aldehydes, the oxide products are formed in the final stage of the ao

88

36

F. Mathey, Tetrahedron, 1973, 29, 707. A. N. Hughes and C. Srivanavit, Canad. J. Chem., 1971,49,879. M. Schlosser, Angew. Chem., 1962, 74,291. L. Maier, Phosphorus, 1972, 1,237. L. Maier, Phosphorus, 1972,1,245. L. Maier, Phosphorus, 1972, 1, 249. J. A. Miller and M. J. Nunn, Tetrahedron Letters, 1972, 3953.

0rganophosphorus Chemistry

78 (HOCH,CH&CH,OH

CI-

pH 1 - 3 y

0

II

(HOCH2CH1)3P=0

(HOCH,CH,) 2PCH,0H

k16

p. (40)

\RO- or

R3NJ

(CHZ=CH)3P=O

0

0 (CH,=CH),P, II

(ClCH,CH,),P=O

(RXCH ,CH 2)3P=0 X = SorO

~

II

Et,N

(CICH,CH,) 2PCH2Cl

CH,Cl

(41)

k-

in ether

0

It

(RXCH,CH,) 2PCHzCl

sequence - details of the role of the halogenophosphine appear in the previous chapter. Phosphorus oxychloride and tertiary phosphines react to give complex salts (43), which are decomposed hydrolytically to phosphine An interesting hydrolysis reaction yields the oxide (44)in what appears to be a stepwise rea~tion.~' ArCH=O

+ PX3

-

0

II

(ArCHX),O + ArCHX2 -+ ArCHXPXz

(42)

A compilation of 13Cn.m.r. data on phosphetan and phospholan oxides and 39 The analysis of sulphides has appeared, together with synthetic 13C n.m.r. spectra has been used to determine the number and identity of stereoisomers in reaction mixtures, and details of 13C shifts and l3GS1P a' as

E. Lindner and H. Beer, Chem. Ber., 1972, 105, 3261. F. G. Mann and A. J. H. Mercer, J.C.S. Perkin I, 1972, 2548. G. A. Gray and S. E. Cremer, J. Org. Chem., 1972, 37, 3458. G. A. Gray and S. E. Cremer, J. Org. Chem., 1972, 37, 3470.

Phosphine Oxides, Sulphides, and Selenides

79

coupling appear in the Physical Methods chapter (Chapter 11). Triphenylstibine oxide (45) has been prepared by the two routes outlined, and the oxidation product ~haracterized.~~ The oxide (45) is monomeric in benzene solution. Ph,SbOH

-% Ph,Sb=O

3 Reactions and Properties

The lithium derivative of 3,4-dimethyl-l-phenylphosphol-3-en 1-oxide (46) reacts with benzonitrile to produce the new heterocycle (4nY4l which has been found to rearrange photochemically. Diazomet hyldiphenylphosphine oxide (48) has been shown to add to the carbonyl group of (49), and the resultant adduct converted to the ring-expanded derivative (50).43

0

II

Ph ZPCHN 2

R

c K $ =Ro

R (50)

(49) 40

43

W. E. McEwen, G. H. Briles, and D. N. Schulz, Phosphorus, 1973, 2, 147. F. Mathey, and J.-P. Lampin, Tetrahedron Letters, 1972, 1949. J.-P. Lampin and F. Mathey, Tetrahedron, 1972, 28, 5367. M. Regitz, W. Disteldorf, U. Eckstein, and B. Weber, Tetrahedron Letters, 1972, 3979.

80

Organophosphorus Chemistry

Further study of the oxidation of diarylphosphine oxides (51) by peroxide compounds (52) has shown that the rate-determining step varies with the nature of R in (52).44The 1,3-0xaphosphol-4-en1-oxide (53) is converted into the bicyclic oxide (54) on treatment with an excess of chlorine.21 Ar,P(OjH

+ ROO-

(51)

__f

Ar,P(O)OH

(52)

n

II 0

Ar

Ar

(53)

(54)

Enamines derived from the oxide (55) have been used in the synthesis of the fused heterocycles (56) and (57).45 The reaction between enamines and diazomethylphosphine oxides (58) does not yield the anticipated pyrazoline (by a 1,3-dipolar addition), but instead yields the phosphine oxides (59).48 Ph-N-N

6

R2NH

(R = cycloalkyl))

ON 'Ph

(55)

0

II

RzPCHN2

'4

46

+

\

,N.-CH=CMe,

-

(57)

0

II

RJT(N2)CH-CHMe,

R. Curci and F. Di Furia, Tetrahedron, 1972, 28, 3905. G. Mark1 and H. Baier, Tetrahedron Letters, 1972, 4439. W. Welter and M. Regitz, Tetrahedron Letters, 1972, 3799.

I

81

Phosphine Oxides, Sulphides, and Selenides

A neat deoxygenation of epoxides by triphenylphosphine selenide (60) has been rep~rted.~’ The reaction results in retention of the epoxide geometry, and is therefore complementary to the deoxygenations by diphenylphosphide (61) and other PI11 reagents, which lead to i n v e r s i ~ n . ~Last * ~ ~year ~ it was reported that the related reaction of triphenylphosphine sulphide (62), also catalysed by trifluoracetic acid, gives good yields of thi-irans,&Oand the contrast is clearly a matter of general interest.

R \Ph,P-

(61)

k.4,

7

CFJCO,H

Triarylphosphineoxides form complexes (63) with toluene-p-sulphonamide, and these are the final products of the reactions of triarylphosphines with chloramine-T Tertiary arsine sulphides are desulphurized by phosphorus Ar,P

+

ClNHSO, -Me

_.)

Ar,P=NSO,

(64)

1

//O”-H \ NH Ar3q -.0--s /

Po f--

Ar,P=O

+

H,NS02

@

Me (63)

Ar,As(S)

+ PCI,

(65)

R,ArAs(S)

+

-

PCI, -+

Ar,As

+ Cl,P(S)

R2ArAsC12

+ [PSI

(66)

6o b1

D. L. J. Clive and C. V. Denyer, J.C.S. Chem. Comm., 1973, 253. E. Vedejs and P. L. Fuchs, J. Amer. Chem. SOC.,1971, 93,4070. E. Vedejs and P,L. Fuchs, J. Amer. Chem. SOC.,1973,95, 822. T. H. Chan and J. R. Finkenbine, J. Amer. Chem. SOC.,1972,94,2880. D. W. Allen, F. G . Mann, and J. C. Tebby, J.C.S. Perkin I, 1972, 2793.

82

Organophosphorus Chemistry

trichloride (see Halogenophosphines, Chapter 3), although the reaction pathway is dependent upon the nature of the arsenic ligands, e.g. (65) and

(66).62 The following physical properties of phosphine oxides have been described during the year : electron paramagnetic resonancessand ultraviolet spectra of oxides (67);s4 n.m.r. spectra of the diphosphine disulphide (68);66 i.r. and Raman spectra of the series of compounds (69);66e.s.r. studies of radicals derived from (70);67 infrared studies of the oxides (71);68 dipole moments of the oxides (72);69and an investigation of the pKa values and other dissociation constants of acyclic phosphine oxides and phosphetan oxides.6o

58

s* 64 66 K8

67 K8

Kg

6o

G. M. Usacheva and G. Kh.Kamai, Zhur. obshchei Khim., 1971,41,2705. S . P. Solodovnikov, A. I. Bokanov, L. I. Chekunina, and B. I. Stepanov. Zzuest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 205. L. I. Chekunina, A. I. Bokanov, and B. I. Stepanov, Zhur. obshchei Khim., 1972,42,995. R. Pantzer, W. Schmidt, and J. Goubeau, Z . anorg. Chem., 1973, 395,262. G. Hagele, R. K. Harris, and J. M. Nichols, J.C.S. Dalton, 1973, 79. A. R. Lyons and M. C. R. Symons, J.C.S. Faraday ZI, 1972, 68, 1589. E. I. Matrosov, E. N. Tsvetkov, D. I. Lobanov, R. A. Malevannaya, and M. I. Kabachnik, Zhur. obshchei Khim., 1972, 42, 1218. E. A. Ishmaeva, R. D. Gareev, G. E. Yastrebova, and A. N. Pudovik, Zhur. obshchei Khim., 1972, 42, 73. A. G . Cook and G. W. Mason, J. Org. Chem., 1972,37,3342.

Tervalent Phosphorus Acids BY 6. J. WALKER

1 Introduction Although the inevitable increase in the number of references appearing in this area has continued, the percentage of significant work has reached an all time low; there is probably a correlation between this and the unusual number of reviews which have appeared during the past year. These include coverage of reactions of tervalent phosphorus acid chlorides with unsaturated acids and amidesl and thermal rearrangements of esters of phosphorous and phosphonous acids.2 Oxidative imination of phosphorus(m) compounds has also been re~iewed.~ 2 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-Attack on Saturated Carbon. The Arbuzov reaction has been investigated with a number of halides including chloroethers,4

(5)

(4)

R. K. Khairullin, Probl. Org. Fiz. Khim., 1971, 109 (Chem. Abs., 1972, 77, 126717). a A. N. Pudovik and I. M. Aladzheva, Khim. Primen. Fosfororg. Soedinenii, Trudy Vsesoyuz. Konf., 3rd., 1965, 98 (Chem. Abs., 1972,77, 74329). ' G . I. Derkach and I. N. Zhmurova, Uspekhi Khim. Fosfororg. Seraorg. Soedinenii, 1970, no. 2, 128 (Chem. Abs., 1973,78, 16260). ' T. F. Kozlova, A. F. Grapov, and N. N. Mel'nikov, Zhur. obshchei Khim., 1972, 42, 1282 (Chem. A h . , 1972, 77, 126778).

83

84

Organophosphorus Chemistry

cc-brom~silanes,~ and trichloromethylamines.6 a-Halogenoureas react with trialkyl phosphites to give the expected phosphonates (l), which were also formed in the reaction of a-hydroxyureas with dialkyl phosphites.' NNN'N'tetramethylchloroformamidiniumchloride (2) undergoes the expected initial reaction with tervalent phosphorus esters to give (3), for example, but this is followed by further dealkylation to (4). Finally, (4) and its analogues are converted into the corresponding anhydrides, e.g. (9,by further reaction with chloroformamidiniumchloride.8 The Arbuzov reaction has been extensively used as a preparative method, for example in the synthesis of 2-alkoxyvinylphosphonates(6); isocyanato0

(Et0)aP

+ XCH,CH(OR),

II

_.)

(EtO)zPCH2CH(OR)2

JA

0

II

(EtO),PCH=CHOR (6)

methylphosphonates (7),1° and, in combination with the Curtius reaction, aminophosphonic acids (8).11 Mixtures of geometrical and structural isomers 0 (EtO),P 3- Me&CH,NHCHO Br-

II

__f

(EtO),PCH,NHCHO

(9) were prepared by the reaction of the dibromide (10) with trialkyl phosphites.l%The photo-Arbuzov reaction has been used to prepare13the anilide of diethyl2-carboxyphenylphosphonic acid (1 1). High yields of 1-substituted n-alkyl chlorides and bromides, with no detectable rearrangement, have been

' E.g. Z. S. Novikova, S. N . Zdorova, and I.

F. Lutsenko, Zhur. obshchei Khim., 1972, 42, 112 (Chem. Abs., 1972, 77, 34633). a V. P. Kukhav, V. I. Pasternak, and A. V. Kirsanov, Zhur. obshchei Khim., 1972, 42, 1169 (Chem. A h . , 1972, 77, 101 790). ' H. Petersen and W. Reuther, Annalen, 1972, 766, 58. ' G. H. Birum and J. D. Wilson, J . Org. Chem., 1972,37,2730. L. Maier, 2. anorg. Chem., 1972, 394, 111. l o U. Schollkopf and R. Schroder, Tetrahedron Letters, 1973, 633. J. P. Berry, A. F. Isbell, and G. E. Hunt, J . Org. Chem., 1972, 37,4396. K . Bergesen and A. Berge, Acta Chem. Scand., 1972, 26, 2975. l a R. Kluger and J. L. W. Chan, J. Amer. Chem. SOC.,1973,95,2362.

Tervalent Phosphorus Acids BrCH,CHMeCH,CH,Br

+

(RO),P

(10)

Me Me

d ‘OR

0’ ‘OR (9)

obtained from the reaction of the corresponding diphenylphosphinite (12) with the appropriate halogen or hydrogen halide.l* Optically active octan-2-01 was converted into 2-chloro-octane by this method with no loss of optical purity. Further details of experiments suggesting a five-co-ordinate phosphorus intermediate in the Arbuzov reaction have appeared.l6 The reaction of the cyclic phosphite (13) with a large excess of alkyl iodide gave the expected

phosphonate (15 ) uia the suggested intermediate (14). Similar experiments with trityl tetrafluoroborate in place of alkyl halide, followed by decomposition of the intermediate (16) with iodide, suggest that the five-co-ordinated intermediate is formed directly from alkyl halide and phosphite and not via an alkoxyphosphonium salt. This is supported by the increasing amount of l6

H. R. Hudson, A. R. Qureshi, and D. Ragoonanan, J.C.S. Perkin I., 1972, 1595. C. L. Bodkin and P. Simpson, J.C.S. Perkin ZI, 1972, 2049. D

86

Organophosphorus Chemistry

trans-isomer in the starting phosphite (13) as the reaction proceeds, since reversible formation of a five-co-ordinate intermediate provides a route for cis-trans interconversions. However, similar results would presumably be obtained if a significant rate difference existed between cis- and transphosphites. Salts of dialkyl phosphites have been reacted with chlorosilanesl6and with 2-chl0roethyldiphenylphosphine~~to give the expected phosphonates. Perhaps surprisingly, a similar reaction with 1,2-dibromoethylcyanidegave1*

-

(EtQ), P-0

-

+ BrCH,CHBrCN

0

I1

---+ (EtO),PCH,CH,CN (1 7)

diethyl 2-cyanoethylphosphonate (1 7), presumably via debromination and addition. Attack on Umaturated Carbon. The reactions of tervalent phosphorus acid derivatives with carbonyl compounds have been reviewed.19 Literally dozens of reports of reactions of tervalent phosphorus nucleophiles with activated olefins have appeared, typical of which are additions to a,%unsaturated ketones,20p-benzoquinone,21pyrylium salts,22and to acrylic acid derivative^.^^ Surprisingly, dialkyl phosphites can be added2*to unactivated olefins (18) to give phosphonates (19), although the reaction may be E. F. Bugerenko, A. S. Petukhova, A. A. Borisenko, and E. A. Chernyshev, Zhur. obshchei Khim., 1973,43, 216 (Clzem. Abs., 1973,78, 1 1 1437). l 7 J. Gloede, J,prakt. Chem., 1972,314 281 (Chem. Abs., 1972,77 140222). B. A. Arbuzov, A. D. Novosel'skaya, and V. S. Vinogradova, Izoest. Akad. Nauk S.S.S.R., Ser khim., 1972, 1153 (Chem. Abs., 1972, 77, 101793). l* I. V. Konovalova and A. N. Pudovik, Uspekhi Khim., 1972,41,799 (Chem. Abs., 1972, 77, 48 545). *O E.g. B. A. Arbuzov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 2545 (Chem. Abs., 1973, 78, 84493); B. A. Arbuzov, E. N. Dianova, and V. S. Vinogradova, Zhur. obshchei Khim., 1972, 42, 750 (Chem. Abs., 1972, 77, 126777); R. S. Tewari and R. Shukla, Indian J. Chem., 1972, 10, 823. I1 I. M. Magdeev, Y. A. Levin, and B. E. Ivanov, Zhur. obshchei Khim., 1972, 42, 2415 (Chem. Abs., 1973, 78,72295). a z S. V. Krivun, 0. F. Voziyanova, and S. N. Baranov, Dopouidi Akad. Nauk Ukrain. R.S.R., Ser. B., 1972, 34, 529 (Chem. Abs., 1972, 77, 101765); S. V. Krivun, 0. F. Voziyanova, and S. N. Baranov, Zhur. obshchei Khim., 1972, 42, 58 (Chem. Abs., 1972, 77,48 587). la L. Maier, Helu. Chim. Acta., 1973, 56, 489. F. Bodesheim, E. Velker, F. Bentz, and N. Guenter, Chem.-Ztg., 1972, 96, 581 (Chem. Abs., 1973, 78, 29910). lo

87

Tervalent Phosphorus Acids 0

0

II

(RO) ,PH

+ CH,=C(CH

,OCOMe)

(1 8)

PhCH;

O

‘P/

II

--+(RO) ,P-CH,CH(CH

,OCO Me)

,

(1 9)

+ R3CH=CHC02R2

R1’ ‘H

PhCHz

\#0

R1’

‘CHR3CH,C0,R2

free radical in character. The reaction of benzyl secondary phosphinites with a/?-unsaturated esters in aprotic provides a new synthesis of phospholan-3-ones (21), while a similar reaction in ethanol gives the phosphine oxide (20), probably by the mechanism shown. Azaphosphole (23) and dihydroazaphospholopyridine(24) are the products from the reactions26of aminophosphine (22) with acrylonitrile and acrylic esters, respectively. Secondary phosphites add to b-nitrostyrene to give the expected phosphonate (25) and a highly coloured polymer.27Rather different reactions take place between the unsaturated nitro-ester (26) and tertiary phosphites.28A high-boiling product was shown to be a mixture of tautomers (27) and (28), while a lower boiling fraction gave after irradiation the N-hydroxyaziridine as 2a

17

28

R. Bodalski and K. Pietrusiewicz, Tetrahedron Letters, 1972, 4209. W. Zeiss and A. Schmidpeter, Tetrahedron Letters, 1972, 4229. T. A. Mastryukova, M. V. Lazareva, and V. V. Perekalin, Izuest. Akad. Nauk S.S.S.R., Ser. khirn., 1972, 1164 (Chem. Abs., 1972, 77, 101794). C. Shin, Y . Yonezawa, and J. Yoshimura, Tetrahedron Letters, 1972, 3995.

88

Organophosphorus Chemistry

(29). Reaction mechanisms involving respectively the aci- and nitro-forms of (26) are suggested. CH ,=CHCN

PhZP-N=C(OEt),

c

(22)

CN (23)

0

II

(R0)zPCHPhCHzNO 2 (25)

RCH,C=CHCO,Et I NO2

1-

(Et),OP=O

* RCH,C-CHCOzEt -I-

II

RCHz M r O p E t +RCH2HCOzE -OdN,

0

ihV

,P(OEt), 0 (27)

RCH2wco2Et N

OH (29)

HON, ,P(OEt), 0

(28)

t

89

Tervalent Phosphorus Acids

The addition of dialkyl phosphites to ethylthioacetylene2Bto give (30) occurs in the opposite sense to the analogous addition to ethoxyacetylene,ao which gives (31). A similar,31 but uncatalysed, addition of phosphite to dimethyl acetylenedicarboxylategives the phosphonate (32). 0

(MeO), P - 0

-

EtSC-CH

----+

II

(MeO),P-CH=CHSEt (30)

1

JEtoC-CH 0

II

(MeO),P-C=CH,

I

0

I1

(RO),PH

+

MeO,C-C~C-COzMe

-

0

II

(ROZ)P-C=CH-C02Me

I

C02Me (32)

As usual, the addition of secondary and tertiary phosphites to Schiff bases has been popular in the Russian literature and the references givens2 are typical. Gross and C ~ s t i s e l l ahave ~ ~ used the related reaction of dichloromethyleneaniline with phosphinites to prepare triphosphorylmethane derivatives (33). A highly convenient synthesis of an optically active a-aminophos0 R'2POR2

+ PhN=CCIz

II PhN=C(PR12)2

0 II RS,PH

0

It

0

II + PhNHC(PR 2) zPR3 (33)

phonic acid has been reported34 through the reaction of Schiff base (34), derived from optically pure a-methylbenzylamine, with diethyl hydrogen *@M. L. Petrov and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 2345 (Chem. Abs., 1973, 78, 58 548).

M. L. Petrov and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 1863 (Chem. Abs., a1

88

1973, 78, 29931). D. A. Nicholson, Phosphorus, 1972, 2, 143. E.g. N. S. Kozlov, V. D. Pak, and E. S. Elin, Vestsi Akad. Naouk Belarus. S.S.R., Ser. khim. Nauuk, 1973, 108 (Chem. Abs., 1973, 78, 97765): N. S. Kozlov, V. D. Pak, and E. S. Elin, Trudy Perm. Sel'skokhoz. Znst., 1970, 68, 19 (Chem. Abs., 1972, 77, 19742); E. E. Nifant'ev and 1. V. Shilov, Zhur. obshchei Khim., 1972, 42, 503 (Chem. Abs., 1972, 77, 101 769). H. Gross and B. Costisella, J . prakt. Chem., 1972, 314, 87 (Chem. Abs., 1972, 77, 126 763). W.F. Gilmore and H. A. McBride, J . Amer. Chem. Soc., 1972, 94, 4361.

Organophosphorus Chemistry

90 0

*

PhCH=N-CHMePh

II Wo)LPH ,40"c t

Pht H-NH-CH MePh I

(34)

(EtO),P=O

phosphite followed by acidic hydrolysis and hydrogenation. Although the - )-amine use of (R)-( +)-amine gives (- )-a-aminophosphonic acid, (9-( gives the (+)-isomer. The reaction of nitrilimines with ap-unsaturated phosphonites leads to phosphorus heterocycles; alkenylpho~phonites~~ give diazaphosphorins (39,

I Ar2

Ph,PNCO

+

PhCCI-NNHPh

(37)

Ft'N=

/FN Ph

and ethynylphosphonites36 give analogous products (36). A similar reaction of the 1,3-dipole derived from (37) with diphenylphosphinyl isocyanate3' gives the heterocycle (38). ES

36

s7

V. V. Kosovtsev, V. N. Chistokletov, and A. A. Petrov, Zhiir. obshchei Khim., 1971,41, 2649 (Chem. Abs., 1972, 77, 34630). L. A. Tamm, V. N. Chistokletov, and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 1864 (Chem. Abs., 1973, 78,29920). V. A. Galishev, V. N. Chistokletov, and A. A . Petrov, Zhtr. ohshckei Khim., 1972, 42, 1876 (Chem. Abs., 1973, 78, 29906).

91

Tervnletit Phosphorlis Acids

The reactions of isocyanates with tervalent phosphorus-nitrogen com~ pounds derived from primary amiiies have been extensively investigated3 8 39 by Hudson and Mancuso; a variety of products were isolated, depending upon the nature of both the isocyanate and the phosphorus Diphenylaminophosphines react to give the urea derivatives (39), but with Ph,PNHR

+ ArNCO

Ph,PNR.CO.NHAr (3 9)

(Et0)tPNHR

(40)

+ PhNCO

1

(EtO),PNR* CO *NHPh

(EtO),P NPh CO *NHR *

(41)

dialkyl phosphoramidites (40), rearrangement to the alternative urea (41) appears to be possible. 1-0xazaphospholine (42) undergoes ring-expansion to (43) with ethyl isocyanate; in the case of the reaction of dialkyl N-arylphosphoramidites with aryl isocyanates, yet another pathway is available to give a-aminophosphonates (44), probably via the mechanism shown. Kinetic

(EtO),PNHPh

+

PhNCO

__f

(EtO),P*NPhCO*NHPh

11 .NP h

PhN- C=NPh

0 NPh

I1 II

(EtO),P-C-N

H Ph

(44) aa 38

R. F. Hudson and A. Mancuso, Phosphorirs, 1972, 1,265. R. F. Hudson and A. Mancuso, Phosphorus, 1972, 1, 271.

92

Organophosphorus Chemistry

studies30 suggest that in all cases initial attack on the isocyanate is by phosphorus rather than by nitrogen, unlike similar reactions of phosphorus compounds, e.g. (43, derived from secondary amines, where initial attack appears to be by nitrogen.

0

II

R2PH

+ CH,(CN),

-

0 NH

II II

R,P-C-CH,CN

The addition of phosphinous acids to the cyano-group to give, e.g. (46), has been The now predictable large number of reports 41 of additions of secondary phosphites to aldehydes and ketones have appeared, mainly in the Russian literature. The reaction of diphenylphosphinite, either as its sodium or magnesium salt, with acetone has been thoroughly in~estigated~~ and shown to give the diphosphine dioxide (48) as well as the expected adduct (47); a similar product was obtained from reactions of the benzyl ester (49) with 0

PhzPz'

-

4- MeKO -+

II

Ph,P-C(QH)Me, (47) 0

+

II

(Ph,PCMe,CH .) ,CQ (48)

0

It

PhpPCO2CH,Fh

acetone and sodium iodide, presumably via debenzylation and decarboxylation to give the phosphinite anion. Further Russian on the reaction of A. N. Pudovik, T. M. Sudakova, 0. E. Raevskaya, and V. A. Fedechkina. Zhur. obshchei Khim., 1972, 42, 1727 (Chem. Abs., 1973, 78, 29923): A. N. Pudovik and T. M. Sudakova, Zhur. obshchei Khim., 1972,42, 1646 (Chem. Abs., 1972,77, 126754). d l E.g. R. S. Tewari and R. Shukla, Labdeu. ( A ) , 1971, 9, 112, (Chem. Abs., 1972, 77, 5574); A. N. Pudovik, M. G. Zimin, and A. A. Sobanov, Zhur. obshchei Khim., 1972, 42,2174 (Chem. Abs., 1973,78, 58543). P. F. Cann, S. Warren, and M. R. Williams, J.C.S. Perkin I , 1972, 2377. ** A. V. Fuzhenkova, A. F. Zinkovskii, L. Y . Savchenko, and B. A. Arbuzov, Zhur. obshchei Khim., 1972,42,999 (Chem. Abs., 1972,77,101773); ibid., p. 754 (Chem. Abs., 1972, 77, 101776).

4o

93

Terualent Phosphorus Acids

trialkyl phosphites with phencyclone (50) adds little to that published prev i o ~ s l y The . ~ ~ same authors have a thermographic study of the reaction of trialkyl phosphites with tetracyclone.

(50)

Similar reactions of aldehydes have been studied, for example diethyl phosphonous acid anilides react 46 with p-nitrobenzaldehyde to give the iminophosphites (51), and other similar work4’ by the same authors is noteworthy if only for the mistakes in the abstract. (R0)ZPNHPh

+ p-OzNCsH4CHO

(RO)zP( :NPh)OCH&H4N02-p (51)

Sidky and co-workers have investigated the reactions of both dL4*and triketones49with phosphites. The o-quinone (52) and trialkyl phosphite give the phosphorane (53), and a similar reaction with dialkyl phosphite gives the

phosphonate (54).48In the latter case alternative mechanisms are suggested, involving either attack of phosphite on the ring adjacent to the carbonyl group or attack on the carbonyl carbon itself followed by rearrangement. The triketone monohydrates (55) and (57) react with trialkyl or dialkyl phosphites A mechanism involving to give the phosphates (56) and (58), re~pectively.~~ initial dehydration to the triketone followed by attack of phosphite at carbonyl carbon is suggested. peri-Naphthinadantrione (59) also reacts with dialkyl phosphites to give a phosphate product (60), but with trialkyl phosphites a reduction to (61) takes place. 44

46

46

47

49

B. J. Walker, in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1973, vol. 4, p. 94. A. V. Fuzhenkova, A. F. Zinkovskii, and B. A. Arbuzov, Zhur. obshchei Khim., 1972, 42, 491 (Chem. Abs., 1972, 77, 87367). A. N. Pudovik, E. S. Batyeva, and V. D. Nesterenko, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1972, 510 (Chem. Abs., 1972, 77, 88604). A. N. Pudovik, E. S . Batyeva, V. D. Nesterenko, and N. P. Anoshina, Sbornik Nekot. Probl. Org. Khim.,1972, 6 (Chem. Abs., 1973, 78, 29909). M. M. Sidkey and F. H. Osman, Tetrahedron, 1973, 29, 1725. M. M. Sidky, M. R. Mahran, and W. M. Abdo, Tetrahedron, 1972, 28, 5715.

94

a,:

Organophosphorus Chemistry

0

+ (RO),PII II

Ph 3C

J or \

(RO) ,P=O

Ph,C

(Rh

' OH

Ph :%C

\

OH

'

0-

J (RO) .,P=O

Ph,C

Jk:: 0

(54)

+

\

(RO)3P

or 0 (55)

-

0

It

(RO) ,PH (56)

0

PhCQ-C(OH)z-COPh (57)

+ (RO),P or 0

I1

(R0)ZPH

I1

+ PhCO-CH-O-P(OR)z

I

co Ph

(58)

95

Terualent Phosphorus Acids

Phenacyl chloride reacts50 with dimethyl phosphite in the presence of piperidine to give dimethyl a-chloromethyl-a- hydroxybenzylphosphona te (62) and a-piperidylacetophenone, illustrating the different preferences of nitrogen and phosphorus nucleophiles. An analogous reaction takes place with benzoylacetonitrile. 0 PhCOCHzC1

II

+ (MeO),PH

OH 0

I

II

Ph-C-P(OMe),

I

CHzCi

3

+ PhCOCHzN n

Paulsen and Thiem have studied the reaction of both tertiary phosphites and secondary phosphite salts with a variety of 0-acetylated hexose 52 With heavy-metal salts of dialkyl phosphites the phosphonate 61

s2

M. A. Ruveda and S. A. de Licastro, Tetrahedron, 1972, 28, 6013. H. Paulsen and J. Thiem, Chem. Ber., 1973, 106, 115. H. Paulsen and J. Thiem, Chem. Ber., 1973, 106, 132.

96

Organophosphorus Chemistry

FH,OAc 0

II

BrHgP(OR), ______f.

or

0

II

AgP(OR),

A

OAc

J. CH,OAc

I

OAc (64)

(63) is the major product; however, reactions with trialkyl phosphites lead to mixtures of (63) and olefin (64).In some cases, depending on the orientation of the adjacent acetyl group, phosphates, e.g. (65), are obtained. CH,OAc

I

(65)

The reactions of both tertiary63 and phosphites with acid chlorides to give the expected acetyl phosphonates (66) have been reported. An analogous product (67) is obtained from the reaction of methyl chloroV. M. D’yakov, N. F. Orlov, G. S. Gusakova, and N. M. Zakharova, Kremniiorg. Mafer., 1971, 139 (Chem. Abs., 1973, 78, 43609). I. L. Knunyants,E. G. Bykhovskaya, and Y.A. Sizov, Zhur. Vesesoyuz. Khim. obshch. im. D . I . Mendeleeua, 1972, 17, 354 (Chem. Abs., 1972,77, 114504).

I8

Tervalent Phosphorus Acids

97 0

II

RCO-P(OR)z (66)

0 (RO),PNHAr

+

CIC0,Me

II

_t

ArNHP(OR)CO,Me

(67)

formate with dialkyl phosphorous acid amides.66Prentice et aZ.66have carried out an extensive study of the reactions of tervalent phosphorus acids with acylating agents and have shown that the initial products in a complex reaction are condensates, e.g. (68), of the phosphorous acid used.

Me (68)

The sterochemistry of the enol phosphates produced in the Perkow reaction has been determined.67 When the carbonyl compound is a ketone (69;

0

(R10)3P4 R2COCHXR3

II (RIO),PO’

11

1

/

(R10)2P0

(71)

R3

\C’

\& H I

R3

R2= alkyl) the (a-phosphate (70) predominates,whereas or-halogenoaldehydes (69; R2=H) give mainly (2)-phosphate (71). The isomer ratios are explained by steric effects in the initial intermediate, a conclusion which is supported by the mixtures of (E)- and (2)-phosphates obtained from methyl ketones. 66

67

A. N. Pudovik, E. S. Batyeva, and V. A. Al‘fonsov, Zhur. obshchei Khim., 1972, 42, 1235 (Chem. Abs., 1972,77, 114503). J. B. Prentice, 0. T. Quimby, R. J. Grabenstetter, and D. A. Nicholson, J. Amer. Chem. SOC.,1972,94,6119. E. M. Gaydon, Tetrahedron Letters, 1972, 4473.

98

Organophosphorus Chemistry

Although N-halogenosuccininiide and trialkyl phosphites form the phosphoramidates (72),68a similar reaction with acyclic N-halogenoamides gives

0

(72)

R2CN 3- HX (73)

II

(RIO).,PH

+ RIX

quite different products including the corresponding nitrile (73) and the dehalogenated amide (74). A mechanism involving an initial step identical to that in the Perkow reaction is po~tulated.~*b 0

II

(R'O).,PH

0

+ RTONHX

II

__f

(R'O)2PX 3- R2CONH2 (74)

A further alternative mechanism for the Michaelis-Arbuzov and Perkow reactions is proposed in a recent review ;69 the formation of a five-co-ordinate intermediate (75) would provide a route to both p-ketophosphonate and vinyl phosphate products. Attack on Nitrogen. The reactioneoof triethyl phosphite with the azide (77) provides a new route to 2-substituted quinolines, via the imidophosphorane (76).New, rather unstable, nucleotide derivatives (78) have been prepared61by (a) E. M. Gaydon, G. Peiffer, A. Guillemonat, and J. C. Traynard, Compt. rend., 1972, 275, C , 547; (6) J. M. Desmarchelier and T. R. Fukuto, J. Org. Chem., 1972, 37, 4218. I s P. Gillespie, F. Ramirez, I. Ugi, and D. Marquarding, Angew. Chem. Internat. Edn., 1973, 12, 91. O0 S. A. Foster, U. J. Leyshon, and D. G. Saunders, J.C.S. Chem. Comm., 1973, 29. G. Baschang and V. Kvita, Angew. Chem. Internat. Edn., 1973, 12, 70.

99

Tervalent Phosphorus Acids

R\+

c-0

J

U(OR),

X-

0

0

It

II

RCOCH,P(OR),

RC-O-P(OR)z

II

.

CH2

+ (EtO),P

o +

__t

N3

(77)

R4 N

the reaction of phosphoryl, sulphonyl, or acyl azides with the corresponding phosphite esters. A variety of products (80)--(83) have been isolated from the reaction of the quinonimine (79) with trialkyl phosphites.62Mechanisms involving initial attack of phosphite at nitrogen or at ring carbon account for all the products. Attack on Oxygen. The kinetics of the oxidation of diary1 phosphinites with butyl hydroperoxide, hydrogen peroxide, and p-nitroperoxybenzoicacid under basic conditions have been The bicyclic hydrazinodiphosphine (84) @a

M. M. Sidky and M. F. Zayed, Tetrahedron, 1972, 28, 5157. R. Curci and F. Di Furia, Tetrahedron, 1972, 28, 3905.

100

Organophosphorus Chemistry

MeT7';r

NMe

NMe

"""\,//

+

0-P(0Me)

I9

(MeO),P=O

+

Tervalent Phosphorus Acids

101

shows reduced nucleophilicity at phosphorus compared with tris(dimethy1amino)phosphine and only reacts with methyl iodide and selenium slowly.64 The endo-peroxide (85), prepared by photosensitized oxygenation of l-benzoxepin, is deoxygenated by trimethyl phosphite to give the unstable aldehyde (87), probably via the betaine (86).66 The decomposition of a large number of different phosphite ozonides to give oxygen and phosphate has been studied.66and the results suggest that two mechanisms are involved. Ozonides derived from phosphites with small rings, or bicyclic structures, decompose by simple extrusion of oxygen from the initially formed adduct (88) without rearrangement, but adducts from phosphites (89) without such

0-0

+

RO...I

P-0

0 3

1

L'OR R

\

0

&wo

pseudorotations

I

0

I

(RO)aP=O

+

0 8

restraints appear to decompose by a lower-energy pathway and show a much greater substituent effect. The last result is in agreement with a requirement for pseudorotation before decomposition. Attack on Halogen. In a series of papers a French group has studied the reaction of phosphites with a-halogen~nitriles~~-~~ and with cc-halogeno-

O7

'* 70

R. Goetze, H. Noth, and D. S. Payne, Chem. Ber., 1972,105, 2637. J. E. Baldwin and 0. W. Lever, J.C.S. Chem. Comm., 1973, 344. L. M. Stephenson and D. E. McClure, J. Amer. Chem. SOC.,1973,95,3074. R. Leblanc, E. Corre, and A. Foucaud, Tetrahedron, 1972, 28, 4039. M. Svilarich-Soenen and A. Foucaud, Tetrahedron, 1972, 28, 5149. R. LeBlanc, E. Corre, M. Soenen-Svilarich,M. F. Chasle, and A. Foucaud, Tetrahedron, 1972, 28, 4431. E. Corre, M. F. Chasle, and A. Foucaud, Tetrahedron, 1972, 28, 5055.

0rganophosp horus Chemistry

102

imides.?l*72 In the case of a-halogenonitriles, attack of phosphite appears to be at halogen and the initial products are iminophosphoranes although CN / (RIO),P 3. R2C(CN),Br + R2C \C--Br

I

in favourably substituted cases these may cyclize.6s When the nitrile also contains an adjacent ester group,Sgp7 0 further reaction of the initially-formed ion pair (91) can lead to N-phosphorylketenimines (92) and to vinyl phos-

J

0

II

R2C= C=N--P(OR')

I

+

o

OR^

II

I

R~C=C-O-P(OR

CO,R~ (92)

I

1)

,

CN (93)

phates (93). The same group is guilty of the contemporary, but reprehensible, habit of publishing very similar work in different journals with their study of the reactions of tervalent phosphorus with a-chlor~succinimides.~~~ 72 Initial

(R'O)aP f

Rs;Rsf *

0

OP(0R'))z

0

R4

Rk (94)

attack of phosphorus again appears to be at phosphorus and vinyl phosphates (94) are isolated. Treatment of bis(dipheny1phosphino)arnine (95) with carbon tetrachloride and various amines gave high yields of the imidophosphine (96). Triazadiphosphorines (97) were obtained from a similar reaction of (95) with bifuncn

M. F. Chasle-Pommeret, M. Leduc, A. Foucaud, M. Hassairi, and E. Marchand, Tetrahedron, 1973, 29, 1419. M. F. Chsde and A. Foucaud, Bull. SOC.chirn. France, 1972, 1535.

Tervnlent Phosphorus Acids HN(PPhJ2

103

+ RNH2

-k

‘CI4*

RNHP(Ph,)

II

C1-

N-P( Ph 3NHR

(95)

(96)

PhZ (97) tional amines, e.g. amidinesi and i ~ o u r e a s The . ~ ~ alkoxyphosphonium salts (99) have been prepared74 by the selective reaction of tris(dimethy1amino)phosphine in carbon tetrahalide with the primary hydroxy-group of the or-D-ghcoside (98). CHzOH

Q yy:

x-

CH,O$(NM~~)~

HOQOMe

HO

OMe OH

OH (99)

(98)

Phosphites react with dichlorofluoronitrosomethane to give adducts (100) of varying stability, probably by initial attack on halogen.7K c1

/

(RO),P 3- CC1,FNO + (RO),P,

ON=CFCl (1oo)

Electrophilic Reactions.-Transesterification reactions of both tertiary 76 and sec0nda1-y~~ phosphites with various diols have been studied and in the latter case the diphosphite product (101) reacted with a number of carbonyl compounds. 0 0

II

II

(MeO)PO(CH ,),OP(OMe) H H

(101) 74 76

77

R. Appel and G. Saleh, Annalen, 1972, 766, 98. B. Castro, Y. Cliapleur, B. Gross, and C. Selve, TetrahedronLetters, 1972, 5001. S. I. Malekin, V. I. Yakutin, M. A. Sokal’skii, Y. L. Kruglyak, and I. V. Martynov, Zhur. obshchei Khim., 1972, 42, 807 (Chem. Abs., 1972, 77, 100370). G . Borisov and K. Troev, Izvest. Otdel. Khim. Nauki, Bulgar. Akad. Nauk., 1971, 4, 369 (Chem. Abs., 1972,77, 100338). G. Borisov and K. Troev, Zzuest. Otdel. Khim. Nauki, Bulgar. Akad. Nauk., 1972, 5, 175 (Chem. Abs., 1973,78,43615).

0rganophosphorus Chemistry

104

Spirophosphoranes, e.g. (102), have been obtained from reactions of various phosphorous acid amides with amino-alcohols and aminophen01s.~~~2-Diethylamino-l,3,2-dioxaphospholanreactss1 with whydroxy-carboxylic acids to give phosphites (103), which react further with

(1 04)

excess hydroxy-acid to give spirophosphoranes (104). Treatment of (104) with diethylamine regenerated the phosphite (103). The 3',5'-cyclophosphite (106)

(107)

'*

R. Contreras, R. Wolf, and M. Sanchez, Synth. Znorg. Metal-org. Chem., 1973, 3, 37 (Chem. Abs., 1973,78,97757). A. N. Pudovik, M. A. Pudovik, S. A. Terent'eva, and E. I. Gol'dfarb, Zhur. obshchei Khim., 1972,42, 1901 (Chem. Abs., 1973,78,43606). M. A. Pudovik, S . A. Terent'eva, and A. N. Pudovik, Sbornik Nekot. Probl. Org. Khim., 1972, 10 (Chem. Abs., 1973,78,29908). M. Koenig, A. Munoz, R. Wolf, and D. Houalla, BUN. SOC.chim. Frunce, 1972, 1413.

Tervalent Phosphorus Acids

105

has been prepareds2 by a similar route from thymidine and the phosphoramidite (105). Oxidation of (106) gave thymidine 3',5'-cyc1ophosphates (107), which were mostly stable to phosphatases. Part of the complex maze of reactions of phosphorus trichloride with amines has been reinvestigated and dichlorodiazadiphosphetidines (log), previously not well characterized, have been prepared by reactions with primary aromatic a n ~ i n e s .A~ ~mechanism involving dimerization of an intermediate imine (108) is proposed (see also Chapter 3). The same group ArNHz

+ excessPC1, * AI-N(PCI~)~

I-,,

ArN-PCI

I I

-=

[ArN=PCI J

[ArN=PCI]

(108)

ClP-NAr (109)

has reported 84 a new general route to 1,3-bisarylsulphonyl-1,3,2,4-diazadiphosphetidines (110) from arylsulphonamides and phosphorodiamidous chloride in the presence of pyridine, probably via a similar mechanism. ArSOaNH2

+ (R1R2N)2PCI

pyridine ___+

ArS02N--PNR1R2

I

I

R1R2NP-NS02Ar (1 10)

Rearrangements.-The intermediate phosphinite ester (111) rearranges 86 by attack at the alkynyl rather than the alkenyl group to give the phosphine oxide (112). A similar [2,3J-sigmatropic rearrangement of (113) gave (1 14). Burgada and his co-workers have continued their investigations of ligand rearrangement in phosphoramidites with a study 86 of biphosphorus compounds of the type (1 15). R*CrC-CH(OH)CH=CHR*

+

Ph2PCl

** G. Bashang and V. Kvita, Angew. Chem. Znternat. Edn., 1973,12, 71. 8a

A. R. Davies, A. T. Dronsfield, R. N. Haszeldine, and D. R. Taylor, J.C.S. Perkin I , 1973, 379. F. L. Bowden, A. T. Dronsfield, R. N. Haszeldine, and D. R. Taylor, J.C.S. Perkin Z, 1973, 516. M. Huche and P. Cresson, Tetrahedron Letters, 1972, 4933. R. Burgada, H. Germa, and M. Willson, Tetrahedron, 1973, 29, 727.

Organophosphorus Chemistry

106 MeCR1=C=CHC(OH)MeR2 3- Ph2PCI

/9\ CMeR2

Ph,P..

II

__f

Ph,P-C-CH=CMeR2

II

C

/ \

Me

I

(113)

R1

(114)

R1

(115)

X, Y = 0 or NH CH,CI

I

-0

SPh

(116)

(117)

Cyclic Esters of Phosphorous Acid.-The cis-thiophenoxyphosphorinan(1 17) was formed stereospecifically in the reaction of benzenesulphenyl chloride with the bicyclic phosphite (1 1 6).87 Two groups have investigated the stereochemistry of 2-dimethylamino1,3,2-dio~aphosphorinans.~~~ Mosbo and VerkadeS8have shown that the mixture of phosphoramidites (119) and (120), formed from the reaction of tris(dimethy1amino)phosphine with the diol (118), has the dimethylaminogroup equatorial in the major isomer (120). The stereochemistries were deduced by oxidation to the corresponding oxides and a comparison of their (Me2W3P 3- CH,(CHMeOH), (118)

\ I

NMe, (1 19) 1

..I (120) 10

W. S. Wadsworth, jun., S. Larsen, and H. L. Horten, J . Org. Chem., 1973, 38, 256. J. A. Mosbo and J. G . Verkade, J. Amer. Chem. SOC.,1972, 94, 8224. W. G. Bentrude and H. W. Tan, J. Amer. Chern. Soc., 1972, 94, 8222.

Tervalent Phosphorus Acids

107 Me

PL g z M e

I

Me Meo,

PA z x M e

I1

OMe

0

dipole moments with phosphates (121) and (122) of known configuration. Similar results have been obtained for the 2-dimethylamino-5-butyl-l,3,2dioxaphosphorinans,89where n.m.r. shows the trans-isomer (123) to be more

stable than the cis-isomer (124). Since the equatorial preference of the dimethylamino-group is in contrast to that of other similar sized groups, a px-dn nitrogen-phosphorus interaction is suggested. The stereochemistriesof various halogenation reactions of cyclic secondary

cis

Organophosphorus Chemistry

108

and tertiary phosphites to give 2-chloro-4-methyl-2-oxo-1,3,2-dioxaphosphorinans (125) and (126) have been reported.g0The configuration of (125) and (126) were allocated on the basis of 31Pn.m.r. and J(PH) coupling constants, and the stereochemistry of substitution of halide in (126) was determinedgOsglby a variety of reaction cycles, for example that shown in the Scheme. These otherwise excellent papers are spoilt by the large number of

(-07; Scheme

typographical errors, including the miraculous interconversion of succinimide and phthalimide! Hydrolysis of the halogenophosphite (127) gives a mixture of secondary probably phosphites (128) and (129) which can be equilibrated by

I

OMe (131)

via the tervalent tautomer (130). The reaction of phosphite (131) with hydrogen bromide gave a 1 : 1 mixture of (128) and (129)through isomerization of the product, but allocation of stereochemistries was still possible on the basis of equilibration studies. A reversal of the previous assignment of stereochemistry for the phosphites (132) and (133) is suggested on the basis of comparisons with (128) and (129) and is consistent with proton chemical shifts in the presence of shift reagents. In both of the above cases the isomers so 91 Oa

W. Stec and M. Mikolajczyk, Tetrahedron, 1973, 29, 539. W. Stec and A. Lopusinski, Tetrahedron, 1973, 29, 547. J. A. Mosbo and J. G. Verkade, J. Amer. Chem. SOC., 1973, 95, 204.

109

Tervalent Phosphorus Acids

with equatorial hydrogen [(129) and (133)] react faster with both water and acetone than those with axial hydrogen, although this is not true for the 5,5-dimethyl isomers (134). The authors suggest that (129) and (133) are more readily converted to the tervalent tautomeric form than their isomers. Miscellaneous Reactions.-Both thallium([) and thallium(III) derivatives of diphenylphosphinite have been prepared.03 A variety of salts have been obtained from the dealkylation of dialkyl phosphites with Group I and I1 metal halides.04 A new route to peptides, involving reaction of suitably protected amino-acids (135) and (136) with diphenyl phosphite and pyridine, 0

II

(Ph0)ZPH

+ ZNHCHR’COPH + NHZCHRTOtX (1 35)

1

(136)

pyridine

0

N+ -0Ph I H-P-OCOCHR~NHZ HO’ ‘OPh (1 37) JNH,CHR‘CO,X

0

PhOH

II + CSH,N + ZNHCHR’CONHCHR‘COZX + PhOP-OH I

H

has been reportedQ6and by analogy with earlier workQ6presumably involves an intermediate (137). A new synthesis of allylic alcohols from ally1 sulphoxides (138) has been Oa

B. Walther, J. Organometallic Chem., 1972, 38, 237. and A. E. Mishkevich, Zhur. obshchei Khim., 1972, 42, 1930 (Chem. A h . , 1973,78,42458). N. Yamazaki and F. Higashi, Tetrahedron Letters, 1972, 5047. B. J. Walker, in ‘OrganophosphorusChemistry’, ed. S. Trippett. (Specialist Periodical Reports), The Chemical Society, London, 1973, vol. 4, p. 114.

@‘ V. V. Orlovskii, B. A. Vovsi, O6

110

Organophosphorus Chemistry 0

0

II

I1

i base

PhSCH,CR'=ZCH,

11,

PhS--CH K'-CR'=CH

N-)i

(1 3 8 )

/lMCO,,P

R'CH=CR'--CH,OH

developedg7and involves alkylation followed by reaction with trimethyl phosphite. The photochemical reaction of 2H-azirines (1 39) with diethyl A r p O N HCH ,Ar

NHCH,Ar2

N (139)

'0

1

0

Ar1C0.NHCH,C0.NHCH,Ar2 +&

Ar1-J&NHCH2Arz

(141)

(140)

phosphite gave benzamido-N-benzylacetamides(141).98The intermediacy of the isoxazole (140) is supported by its conversion to (141) on warming with diethyl phosphite. Tetramethylammonium t-butyl phosphonate (142) is a convenient phosphorylating agent for alkyl iodidesg9since the initially formed alkyl t-butyl Bu'O e Me,N

\pH

-*'

But0

0 _t RI

H '

0

\pN

RO/

\H

CF,CO,H

/OH

+ ROP,

11

0 (143)

H

ap;.. a*" (142)

+

0I-I

(144) Et,N

O7

(145) D. A. Evans, G. C. Andrews, T. T. Fujimoto, and D. Wells, Tetrahedron Letters, 1973, 1385; ibid., p. 1389. T. Nishiwaki and F. Fujiyama, J.C.S. Perkin I , 1972, 1456. A. Zwierzak and M. Kluba, Tetrahedron, 1973, 29, 1089.

Tervalent Phosphorus Acids

111

phosphonates readily give monoalkyl hydrogen phosphonates (143) on treatment with trifluoroacetic acid at room temperature. What is claimed to be the first stable intermediate containing six-coordinated phosphorus (145) has been isolated from the reaction of the o-phenylenephosphonite (144) with catechol in the presence of triethylamine.lOO

3 Phosphonous and Phosphinous Acids and Derivatives Extensive reviews of both phosphonousIo1 and phosphinouslo2acid derivatives have appeared. The kinetics of oxidation of phenylphosphonous acid by vanadium(v) have been studiedlo3and the rate of oxidation shown to increase with increasing hydrogen ion concentration. The results of a studylo4of catalysis of tetramethyl-D-glucosemutarotation by oxyacids, including benzenephosphinic acid, suggest that strong oxy-acids act as tautomeric catalysts for the mutarotation in non-polar solvents. 0

I\ I

RPH

F

(146)

Previously unknown phosphonous acid fluorides (146) have been prepared by the simultaneous reaction of dichlorophosphines with hydrogen fluoride and water.Io5The reaction of diphenylphosphinic acid with acetic anhydride 0

II

PhzPH

+ MeCO.O.COMe

pyridine

[Ph,P-O*COMe]

+ AcOH

(147)

0

II

PhZP-PPhz (148)

and pyridine to give tetraphenyldiphosphine monoxide (148) is thought to involve the acetoxyphosphine (147) as an intermediate.lo6 M. Wieber and K. Foroughi, Angew Chem. Internat. Edn., 1973, 12,419. A. W. Frank, Org. Phosphorus Compounds, 1972. 4,255. loa L. A. Hamilton and P. S. Landis, Org. Phosphorus Compounds, 1972, 4, 463. loS K. K. Sen Gupta, J. K. Chakladar, B. B. Pal, and D. C. Mukherjee, J.C.S. Perkin 11, 1973, 926. lo' P. R. Rong and R. 0. Neff, J. Amer. Chem. SOC.,1973,99,2896. I o 6 U. Ahrens and H. Falius, Chem. Ber., 1972, 105, 3317. l o 6 S. Inokawa, T. Tanaka, H. Yoshida, and T. Ogata, Chem. Letters., 1972,469. loo

lol

6 Q ui nquevale nt Phosphorus Acids BY N.

K. HAMER

1 Phosphoric Acid and Derivatives Synthetic Methods.-There has been comparatively little work reported in this area during the past year. A few new active esters have been investigated as phosphorylating agents and there have been some practical extensions in the use of protecting groups. AIso included are examples where either the reaction type or the product have novel features even when the preparative method is severely limited in scope.

(1)

x

= 0

(2)

x

=

s

The phosphorylated derivatives (1) and (2) of N-hydroxy- and N-mercaptosuccinimide, respectively, have been prepared and examined as potential phosphorylating agents.' Although (1) was obtained by condensation of N-hydroxysuccinimideand a dialkyl phosphate with DCC, this procedure was unsuccessful for (2), which is easily produced, however, by reaction of N-chlorosuccinimide on 00-dialkyl phosphorothioates. Compound (1) phosphorylated primary alcohols in the presence of 2,6-lutidine in tolerably good yields but is unfortunately very much less effective for phosphorylating nucleotides. The thio-ester (2) is also a phosphorylating agent but gives mixtures of several products with alcohols, possibly by dealkylation of reactants (or products) by the N-mercaptosuccinimide liberated. Among other reported phosphorylating agents the cyclic ester (3) appears to be an elegantly designed reagent a for the preparation of OS-diesters of phosphorothioic acid and thence, by iodine oxidation, of monoalkyl phosphates. Use of primary amines in the alcoholysis of the triester (4) demonstrates (as has been shown in several solvolytic studies) that amines prefer to react with T.M.Chapman and D. G . Kleid, J. Org. Chem., 1973,38,250. * M. Iio and M.Eto, Agric. and B i d . Chem. (Japan), 1973, 37, 115.

112

113

Quinquevalent Phosphorus Acids

*yyAc Y

(ArO),bO

phosphate esters bearing a relatively poor leaving group by general base catalysis rather than by nucleophilic attack. A phosphorylating intermediate is formed3 from the N-phosphorylated 1,4-dihydropyridine ( 5 ) on oxidation (Ce4+,Ph3C+,or 02-hv), but appears to be of little practical value. Irradiation of (5) under N2 also gives P-N cleavage but results in a much less efficient reaction. An improved procedure has been reported for the removal of the phenylthioethyl protecting group in polynucleotide syntheses.* Use of N-chlorosuccinimide in neutral aqueous solution results in oxidation to the sulphone 0

II R’ SII

0

0

It I

CH2CH20P-OR2

+ R20POa2-

0-

(7) S. Matsumoto, H. Masuda, K . 4 . Iwata, and 0. Mitsunobu, Tetrahedron Letters, 1973, 1733. ‘ K. L. Agarwal, M. Fridkin, E. Jay, and H. G. Khorana, J. Amer. Chem. SOC.,1973,95, 2020.

114

Orgunophosphorus Chemistry

(a,

which undergoes base-catalysed elimination with sodium hydroxide much more readily than the sulphoxide formed by periodate oxidation. A protecting group which is claimed to facilitate product isolation from phosphorylation The arylaminoprocedures by zwitterion formation (7) has been e~amined.~ group is readily removed by treatment with isopentyl nitrite.

Some new phosphorimides have been reported, of which (8) is formed by reaction of o-aminophenol with phosphorus pentachloride and may prove, on further investigation, a useful phosphorylating agent. With alcohols and a tertiary base it gives (9),which can also be made by reaction of o-azidophenol R-CBr(CN),

(R0)3p*

R-C

FN %-Br /

(RO),P=N (10)

and a dialkyl phosphorochloridite. Phosphorimides of the type (10) are also formed in reaction of several bromomalononitriles with trialkyl phosphates.' The most general route to N-phosphorylaziridines appears to be reaction of NN-dibromophosphoramidatediesters with an appropriately substituted olefin followed by treatment of product (1 1) with methoxide.8 ON-Ethanola-

(1 1 )

T. Hata, I. Nakagawa, and N . Takebayashi, Tetrahedron Letters, 1972, 2931. M. I. Kabachnik, N. A. Tikhonina, B. A. Korolev, and V. A. Gilyarov, Doklady Akad. Nauk S.S.S.R., 1972, 204, 1352 (Chem. Abs., 1972, 77, 101767). R. Leblanc, E. Corre, and A. Foucaud, Tetrahedron, 1972, 28, 4039. * A. Zwierzak and S. Zawadzki, Synthesis, 1972, 416.

115

Quinquevalent Phosphorus Acids

H 2 0 3PNHCH2CH20PO3H2

mine diphosphate (12) can be obtained9 in good yield by reacting the parent amine with phosphoric acid with removal of the water formed by distillation.

(13)

When the sulphenyl chlorides (13) are refluxed in toluene, the OOS-triesters are formed in a reaction which is presumably radical in nature.lO This reaction appears to be adaptable to other hydrocarbons which possess readily abstractable hydrogen atoms. Also prepared from the corresponding sulphenyl chloride and silver cyanide is the first reported phosphoryl thiocyanate ester (14)11 which, even at room temperature, isomerizes to the corresponding isothiocyanate(15). (Me $-CH

/p

H0

20) 2P\

(MeK-CH 20)2P\

SCN

NCS

(14)

(1 5 )

Finally, it has been reported that trifluoromethyl phosphorodifluoridate (16) is formed on reaction of trifluoromethyl hydroperoxide with the mixed anhydride (17).12 CFSOOH

+ F2P-O-PF2

II

__f

CFSOPOFS

0

Solvolyses of Phosphoric Acid Derivatives.-There has appeared a detailed review of quinquecovalent intermediates which may be involved in nucleophilic displacements on Pv acids and related While much of the basic material is not new the review makes a systematic attempt to derive some useful generalization on the behaviour of cyclic esters. In particular the authors point out that, in the most general case, the rates, stereochemistry, and position of cleavage are a function of many rate constants (most of which lo

I1 ' I I8

P. V. Laakso, U.S.P. 3697626 (Chem. Abs., 1973,78, 3745). Hercules Inc., Fr.P. 2082884 (Chem. A h . , 1972, 77, 151465). A. Lopusinski and J. Michalski, Angew. Chem. Internut. Edn., 1972, 11, 838. P. A. Bernstein and D. D. Desmarteau, J. Fluorine Chem., 1973, 2, 315. P. Gillespie, F. Ramirez, I. Ugi, and D. Marquarding, Angew. Chem. Internut. Edn., 1973, 12, 91.

116

Organophosphorus Chemistry

cannot be measured) and only with suitable simplifying assumptions can the available experimental data be rationalized. It seems probable that future work in this field will aim at establishing how many of these assumptions will prove to be legitimate. Some aspects of this question have also been discussed briefly by Brown and Hudson,14 particularly in those compounds where the phosphorus is present in a four- or five-membered ring. (Et0)zPOF

* (EtO),PO,H

+ HzO K

+ HF

= 106

Scheme 1

The hydrolysis (Scheme 1) of diethyl phosphorofluoridate has been shown to be reversiblelSwith an equilibrium constant of lo6,which is far larger than the value 4.3 found for phosphorofluoridic acid itself. This difference is plausibly attributed to smaller solvation energy of the diethyl ester relative to the free acid rather than to electronic effects. In this investigation the very small concentrations of diethyl phosphorofluoridate present at equilibrium were measured by its inhibition of cholinesterase. The rates of hydrolysis of several phosphorochloridate esters and amides have also been measured and the effect of substituents on the values of ACp* and AS*for the hydrolysis discussed.la Methanolysis of cyclic trimetaphosphate (18) under acidic conditions gives only monomethyl phosphate,17 suggesting that the linear polyphosphates

0

z :F

+ MeOPO,H,

+

II

MeOPOPO,H,

I

OH

R Y + MeOP--O--~-OP03 I

OH

I

OH

MeQPO,H,

resulting from the initial attack must solvolyse faster than (18). More surprising is the observation that monomethyl phosphate is also a major product under basic conditions; however, here there are also formed considerable quantities of the diphosphate (19) with a little of the linear triphosphate ester l4

l6

l7

R. F. Hudson and C. Brown, Accounts Chem. Res., 1972,5,204. H. C. Froede and I. B. Wilson, J. Amer. Clzem. SOC.,1973, 95, 1987. E. C. F. KO and R. E. Robertson, Cunud. J. Chem., 1973,51, 597. D. B. Trowbridge, D. M. Yamamoto, and G . L. Kenyon, J. Amer. Chem. Soc., 1972, 94, 3816.

Quinquevalent Phosphorus Acids

117

"o\p/o OH

"9( >,OH 04 \/\o (21)

~--a--b :;o: base

OH

b+ MeOP II

0

II

0

0 mH2

II

PhO-P-OSOa-

I

0(22)

(20). The phosphonate analogue (21) behaves as expected to give the same products of P-0 cleavage with both acid and base. Further studies of the mixed anhydride (22) have revealed that in acetonitrile containing a small amount of water the hydrolysis is catalysed by Mgz+, the catalysis falling with increasing water concentration in the medium.l* It appears that (22) forms a 1 : 1 complex with Mgz+, whose formation is inhibited by water which complexes more strongly with the cation. The hydrolysis of tris-2,6-dimethoxyphenylphosphate in the pH range 7M-HCl+ pH 7.5 proceeds through the neutral molecule and the conjugate acid.l9 Similar behaviour is shown by the corresponding diester whose rate, unlike that of diphenyl phosphate, shows a simple dependence on Ho.aoThe elimination of p-nitrophenate anion from (23)in base is strongly catalysed by

micelles of the quaternized ethanolamine (24),21but since the reactions of (23) with fluoride ion is not catalysed under these conditions it seems probable that (24) acts as a nucleophile, deriving assistance from the hydrophobic interactions of the long alkyl chain with the aryl groups. Investigations into the hydrolysis of monoaryl phosphates catalysed by alkaline phosphatase (from E. coli.) at pH 8 have shown22that the reaction is rather insensitive to substituents (p = + 0.43), that tris-buffer is phosphorylated under the conditions of the reaction, and that the enzyme is inhibited by phenylphosphonic acid. It was suggested that this enzyme-catalysed reaction involved co-ordination of the substrate to Zn2+but is different from the Znz+-catalysedsolvolysis of phenyl phosphoramidate, which has a negative p value. The cyclic mixed anhydride (25), prepared by pyrolytic elimination of methyl chloride from (26), is claimedz3 to be more reactive to hydroxylic nucleophiles than any other known phosphate ester. Attack, even by tertiary la

so s1

aa *a

E

W. Tagaki, Y. Asai, and T. Eiki, J. Amer. Chem. SOC.,1973,95, 3037. M. M. Mhala and S. Prahba, Indian J . Chem., 1972, 10, 1073. M. M. Mhala and S. Prahba, Indian J . Chem., 1972, 10, 1002. C. A. Bunton and L. G . Ionescu, J . Amer. Chem. SOC.,1973, 95,2912. A. Williams, R. A. Naylor, and S. G . Collyer, J.C.S. Perkin ZI, 1973, 25. F. Ramirez, S. Glaser, P. Stern, P. D. Gillespie, and I. Ugi, Angew. Chem. Internat. Edn., 1973, 12, 66.

Organophosphorus Chernisfry

118

(26)

OMe

)fJ
(27)

alcohols, occurred exclusively at phosphorus, but tertiary mines gave dealkylation. On heating, (25) underwent decarboxylation to the enediol phosphate (27). Rate and product studies on the hydrolysis of methyl OS-ethylene phosphorothioate (28a) show that as with methyl ethylene phosphate (28b) there are fast acid- and base-catalysed reactions together with

(28) a; X = S

b;X = 0

a much slower water reaction.24 Unlike (28b), no exocyclic cleavage was observed at any pH in therange 0-14.5, but the acid-catalysed reaction, unlike the neutral or base catalysed, did give substantial endocyclic P-0 cleavage. These results were discussed in terms of quinquecovalent intermediates and the relation between these intermediates and those in the base solvolysis of S-2-hydroxyethyl methyl phosphorothioate was considered. There have been reported further studies on intramolecular catalysis of the hydrolysis of phosphate esters. At pH 7.6 the three esters (29), (30), and 0 0

II

NH-P-OPh

(3 1) 25 undergo rapid hydrolysis with loss of phenol. The solvolysis is catalysed by Zn2+ and, to a lesser extent, by Mg2+; moreover, in the presence of D. C. Gay and N. K. Hamer, J.C.S. Perkin 11, 1972, 929. J. J. Steffens, E. J. Sampson, I. J. Siewers, and S. J. Benkovic, J. Amer. Chem. Soc., 1973, 95, 936.

Quinquevalent Phosphorus Acids

119

hydroxylamine small amounts of hydroxamic acid were detectable. These observations imply that nucleophilic catalysis by the neighbouring carboxylate is occurring and that this is assisted by the metal ion - possibly by stabilization of the quinquecovalent intermediate. The proposed cyclic ester from (29) (and probably the others behave similarly) was found to undergo nucleophilic attack almost exclusively at phosphorus,26and this is consistent with the behaviour of these cyclic mixed carboxylic phosphoric anhydrides. Under acidic conditions, (29) underwent the expected P-N cleavage. Intramolecular general acid catalysis by the protonated nitrogen appears to operate in the hydrolysis of (32) when n = 1 or 2, but from a study of several substituted

(3 3)

derivatives it was concluded that when It= 3 the normal phosphate monoester monoanion mechanism occurs.27Further studies on the Cu2+-catalysedsolvolysis of 8-hydroxyquinoline phosphate esters (33) has shown that a fairly reactive phosphorylating intermediate is In pyridine in the presence of a small amount of water the main product was the dialkyl pyrophosphate, whereas in ethanolic solution the mixed phosphate diester was formed. The base hydrolysis of a series of NN-diaryl phosphordiamidate esters (34) shows a rate difference which can be explained in terms of two pathways,

rx(

X (PhNH),Pc ’OAr (34)

x

CH CM

= 0 or S

NH,(C HJ ,NH(CH z ) 3 - ~ -

//O P” / \ NH OH

*( E. J. Sampson, J. Fedor, P. A. Benkovic, and S. J. Benkovic, J. Org. Chem., 1973, 38, 1301.

Y. Murakami, J. Sunamoto, and N. Kanamato, Bull. Chem. SOC.,Japan, 1973,46,871. K. Nagasawa and H. Yoshidorne, Chem. and Pharm. Bull. (Japan), 1972, 20, 1840 (Chern. Abs., 1972,77, 129771).

120

Organophosphorus Chemistry

one of which is first order and the other second order in hydroxide It was shown that the second order term was very sensitive to the nature of the substituents (p = 3.08) and that this term was relatively more important in the P= S compounds. These results are consistent with a mechanism in which the second-order term represents a unimolecular elimination of the dianion whereas the first-order term represents an sN2(P) attack on the neutral molecule by hydroxide. Another phosphordiamidate ester whose hydrolysis has been examined (unfortunately without detailed kinetic studies) is the cytotoxic ester (35).30 At 100 "C the intermediate (36) can be detected after a short time which, on prolonged reaction, is converted into (37); it seems probable, therefore, that the initial step involves an intramolecular alkylation to give (38). Other phosphate esters whose hydrolyses have been studied include 2,2,2trichloroethyl phosphate which, at pH 3.5, hydrolyses by P-0 cleavage of the neutral and diallyl phosphate, which undergoes C-0 fission from both the neutral species and the conjugate The elimination of inorganic phosphate from glyceraldehyde 1-phosphateis catalysed by aromatic amines (39) with the p-substituents being more efficient than 0- or m-subs t i t ~ e n t sIt . ~seems ~ clear that intramolecular catalysis of the p-elimination

+

N H , C H 2 ~ ~ 2 ( ~ ~ ~ ~ 2 ~ ~ z ) (40)n = 3 or 4 (39) R = OH or NH,

from the presumed Schiff base intermediate is unimportant. Polyamines of the type (40) increase the rate of hydrolysis of ATP,34an effect which is attributed to hydrogen-bonding between the amine and the adenine moiety assisting nucleophilic attack on phosphorus. The stereochemical consequences of nucleophilic displacements on phosphates provide important evidence on the intermediates and continue to be

i-T:Q:' Me

(40

a1

ax 83

(42)

A. Williams and K. T. Douglas, J.C.S. Perkin II, 1973, 318. J. K. Chackrabarti and 0. M. Friedman, J. Heterocyclic Chem., 1973, 10, 55. Y.Murakami, J. Sunamoto, and N. Kanamoto, Chem. Letters, 1972, 699. M. M. Mhala and S. B. Saxena, Indian J. Chem., 1972, 10, 703. I. V. Mel'nichenko, N. Y. Kozlova, and A. A. Yasnikov, Ukrain. Khim. Zhur., 1972, 38, 1152 (Chem. Abs., 1973,78, 83540). S. Suzuki, T. Higashiyama, K. Ueda, and A. Nakahara, Bull. Chem. SOC.Japan., 1972, 45, 1579.

Quinquevalent Phosphorus Acids

121

intensively studied. Although both isomers (41) and (42) react stereospecifically with piperidine to give inverted product, with methanol in the presence of triethylamine the isomer (41) gives almost exclusive inverted product whereas the reaction of (42) is less stereospe~ific.~~ It seems likely that this differing behaviour reflects variations in the rates of breakdown : rate of pseudorotation of the quinquecovalent intermediates. A somewhat similar result is observed with nucleophilic substitutions on (43), which proceeds

c1 1

0

Me0

0

OMe OMe (43)

(44)

Me (45)

with > 96 % inversion with ethanol or dimethylamine yet predominant retention is observed with phenylmagnesium bromide.3s In this last case it is probable that co-ordination of oxygen to magnesium may stabilize the quinquecovalent intermediates ; it should in any case increase the apicophilicity and thus the number of favourablc pseudorotations. Related to these questions is the observation that the isomers (44)and (45) are configurationally stable when X is a poor leaving group but readily interconvert when X = C1, p-nitrophenoxy, e t ~ . ~It' is possible, as was suggested, that this interconversion (which is acid catalysed) proceeds through a phosphorylium cation, but until more definite evidence for such intermediates is found it seems preferable to attribute this also to reversible formation and breakdown of a quinquecovalent intermediate. Reactions of Phosphoric Acid Derivatives.-The use of hexamethylphosphoramide (HMPA) as a solvent continues to be developed and it has become clear that, at reflux temperature, it can behave as a rather versatile reactant. Thus cyclic ketones are converted into enaminesS8and primary amides into substituted guanidines (Scheme 2)3g although in the latter case yields are good only if R2=aryl. Under similar conditions primary amines can give fourmembered ring compounds (46) 39 and ketoximes undergo Beckmann

l6

87

a*

C. L. Bodkin and P. Simpson, J.C.S. Perkin 11, 1973, 676. T. D. Inch and G. J. Lewis, Tetrahedron Letters, 1973, 2187. W. S. Wadsworth, jun., J.C.S. Perkin 11, 1972, 1686. R. S. Monson, D. N. Priest, and J. C. Ullrey, Tetrahedron Letters, 1972, 929. E. B. Pedersen, N. 0. Vesterager, and S . - 0 . Lawesson, Synthesis, 1972, 547; N. 0. Vesterager, R. Dyrnesli, E. B. Pedersen, and S . - 0 . Lawesson, ibid. p. 548.

Organophosphorus Chemistry

122

(46) rearrangement,40in a convenient one-stage reaction under non-acidic conditions. Most of these reactions would seem to involve an initial trans phosphorylation of the substrate and it is well established that 0-phosphorylated oximes rearrange thermally to (47).41 Oxidation of the N-methyl groups of Me

\

C=N-

OPO(OEt),

Ar/

4 ArN=C-OPO(0Et) I

,

Me

(47) HMPA to formaldehyde has been observed to occur with oxygen,42presumably by a radical process. Finally the bis(dimethy1amino)phosphoryl group has been proposed as a useful protecting group for alcoholic hydroxygroups or ketones (the latter as a phosphorylated e n ~ l )This . ~ ~can be removed by hydrolysis or may, if required, be reduced to the hydrocarbons with Li-NH 3.

(48) The peroxyphosphoric ester (48) reacts with benzene in the presence of aluminium chloride in the same manner as a trialkyl phosphate to give the alkylbenzene, but with phenylmagnesium bromide attack on oxygen occurs giving t-butyl phenyl ether and dialkyl phosphate anion.44Pyrolysis of the

+,

/9?,Me

m , p \

9-0

(EtO),P02-

--+

+ MeCOEt

Et

(49) 40

41

4z

R. S. Monson and B. M. Broline, Canad. J. Chem., 1973, 51,942. E. M. Bellet and R. Fukuto, J . Agric. Food Chem., 1972, 20, 931. J. Y. Gal and T. Yvernault, Compt. rend., 1972, 275, C, 379. R. E. Ireland, D. C. Muchmore, and U. Hengartner, J . Amer. Chem. SOC.,1972, 94, 5098.

44

G. Sosnovsky, E. H. Zaret, and M. Konieczny, J. Org. Chem., 1972, 37,2267.

123

Quinquevalent Phosphorus Acids

related ester (49) leads cleanly to butan-Zone and dialkyl phosphate, probably through a cyclic transition

,

OAr2

Scheme 3

Irradiation of triaryl phosphates gives diphenyl derivatives (Scheme 3) in a process which appears to be intramolecular since when mixtures of two esters were irradiated, no cross products were formed.4s Electron-donating substituents on the rings increase both the yield and the quantum yields. Although it seems clear that the solvent (EtOH) acts as a reducing agent, no ArH was found in the product and on the data available it was suggested that the coupling involved two axyl radicals in a tight solvent cage. Studies have also been reported on the photolysis of aqueous solutions of glycerol 1- and 2-phosphates at 253 nm.47These reactions have low quantum yields (0=0.01 under N2;0.02-4.03 under 0,) and result in loss of inorganic phosphate to give glycidol (40 %), glyceraldehyde, and dihydroxyacetone (10 %), and a little glycollic acid. It was proposed that the excited substrate broke down by two distinct pathways (Scheme 4), the major one (-80%) giving glycidol and Glycerol I-phosphate

GlyceroI 2-phosphate

Y

Jhy Intermediate

/0-15%

Dihydroxyacetone phosphate

k-s0;4

Glycidol

+ H,P04

Scheme.4

inorganic phosphate and the minor one (10-15 %) giving the labile dihydroxyacetone phosphate, which was detected as an intermediate. The phosphoramidothioate ester (50) undergoes a remarkable rearrangement on oxidation with rn-chloroperbenzoic acid to give (51) and (52).48To account for this it was proposed that initial epoxidation of the P=S occurred to give (53), which may either extrude S or rearrange by migration of the amide group from phosphorus to sulphur. Ketones may be converted into thioketones by reaction with 00-dialkyl phosphorodithioate~~~ in a reaction Is I6

4u 4s

H. Binder and R. Fischer, 2.Naturforsch., 1972, 27b, 153. R. A. Finnegan and J. A. Matson, J. Amer. Chem. SOC.,1972,94,4780. J. Greenwald and M. Halmann, J.C.S. Perkin 11, 1972, 1095. M. A. H. Fahmy and T. R. Fukuto, Tetrahedron Letters, 1972, 4245. S. Oae, A. Nakanishi, and N. Tsujimoto, Chem. and Ind., 1972, 575.

124

Organophosphorus Chemistry

1

ArOCON-P(OMe)z

Me

RC0,H

~

ArOCONSPO(OMe)2

Me

(50)

+ ArOCONPO(OMe), Me (52)

7%

ArOCON-P(0Me)

which is formally similar to the Wittig reaction, and the unstable intermediate (54) was isolated in the reaction with benzophenone. The mixed anhydride (55) undergoes rearrangement to the isothiocyanate (56) with triethylamine,KO

but it was not established whether the reaction was intramolecular. If initial attack of the amine occurs on the carbonyl, an intermolecular reaction seems inevitable; if on the aziridine ring, an intramolecular reaction is possible.

(Et0)2PSCH2CHZNCO

II

S

(56) 6o

E. S. Gubnitskaya, V. F. Gamaleya, and V. A. Shokol, Zhur. obshchei Khim., 1972,42, 21 12.

Quinquevalent Phosphorus

125

Diethyl phosphorocyanidate (57) (from triethyl phosphate and cyanogen bromide) has been proposed as a useful reagent for peptide coupling; yields are good and no racemization is observed.61Diphenyl phosphorazidate (58)

(58)

is useful for performing the Curtius reaction on carboxylic acids under mild condition^.^^ This reaction is best carried out in t-butanol to give the carbamate ester, but for half-esters of malonic acid it was necessary to add the alcohol after reaction of the other components.6SOther active phosphate esters which have been studied are the en01 phosphates (59), which are vinylogous

(59)

mixed anhydrides and undergo facile disproportionation to the symmetrical pyrophosphate and (60).spNucleophiles were found to attack (59) by addition to C=C rather than at phosphorus. Alkyl phosphorodichloridates can be converted into symmetrical dialkyl pyrophosphates by reaction with dimethyl sulphoxide with production of a miscellany of S-containing product^.^^ A tentative mechanism was proposed as shown in Scheme 5. Diethyl phosphorochloridate and its P=S analogue O ROP,

c1

c1.

O Cl

Me,SO*

RO-#/

'05&' I

0 II ROP-C1

@-H

I

OH

0 0 II It RO-P-0-P-OR I i OH OH

+ MeSCH,Cl Scheme 5

6s &4 cK

S. Yamada, Y. Kasai, and T. Shioiri, Tetrahedron Letters, 1973, 1595. T . Shioiri, K. Ninomiya, and S Yamada, J, Amer. Chem. SOC.,1972, 94,6203. S. Yamada, K. Ninomiya, and T. Shioiri, Tetrahedron Letters, 1973, 2343. G. W. Fischer and P. Schneider, Chem. Ber., 1973, 106,435. M. A. Ruveda, E. N. Zerba, and E. M. de Moutier Aldao, Tetrahedron, 1972,28,5011.

126

Organophosphorus Chemistry

H

(61) appear to give a 1 : 1 adduct with the diamines (61),56which is hydrolysed back to the parent amine by water but on standing the adduct is converted into the expected phosphoramidate. These adducts appear to be N-phosphonylated pyridinium chloride species stabilized by hydrogen-bonding. In the reaction of dialkyl phosphorochloridates with trialkyl phosphates (or P=S analogues), scrambling of the alkyl groups occurs to give mixtures of several fully esterified phosphate^.^^ Investigations have been carried out into the mechanism by which the novel product (62) is formed (6% yield) from reaction of thiophosphoryl

NMe, PSCl3

1-

H-

0 - aKcH20

Me,,

,CHZ

d

NMe, /

NMe,

NMe,

Me

Me

-HH-efc.b

/

Me

Me

Me (63)

(64)

with NN-dimethyl-p-toluidine.From these studies it is proposed that initial hydride transfer from the base occurs to give (63), which is converted into (64) and thence into (62). Another reaction which leads to a

(65)

Y.N. Forostyan, E. I. Efimova, E. P. Kukhta, and I. I. Soroka, Zhur. obshchei Khim., 57

1971, 41, 2438. A. Zwierzak, Phosphorus, 1972, 2, 19. T. A. Cameron, C. Y. Cheng, T. Demir, K. D. Howlett, R. Keat, A. L. Porte, C. K. Prout, and R. A. Shaw, Angew. Chem. Internat. Edn., 1972, 11, 510.

Quinquevalent Phosphorus Acids

127

product of unusual structure (65) is that of pyrophosphoryl fluoride with (66).69 The isolation of an anion of a phosphoramidic chloride has been reported reaction of (67) with aniline in the presence of triethylamine gave the salt (68). From a study of a series of the related phosphorimidic chlorides (69) it

was found that the equilibrium favoured the form in which the P=O was attached to the P atom bearing the more electronegative substituents.B1 Trialkyl phosphates may be converted into trialkoxyaryloxyphosphonium salts (70) by treatment with benzenediazonium hexachloroantimonate.6a (RC),PO

+ PhN:

SbCI;

c_f

(RO)$OPh

SbCI,‘

(70) 2 Phosphonic and Phosphinic Acids and Derivatives

Synthetic Methods.-A fairly general synthetic route to aminophosphonic acids has been reported by reaction of esters of an appropriate bromo-acid with triethyl phosphite followed by a Curtius Some of these aminophosphonic acids are reported to show polymorphi~rn.~~ Asymmetric induction is observed in the reaction of the chiral imine (71) with diethyl phosphonate, and removal of the a-methylbenzyl group by hydrogenolysis H

PhCH=N-C,,

/

‘Me Ph

(71) 69

6o

H. W. Roesky and L. F. Grimm, Angew. Chem. Internat. Edn., 1972,11,642. V. P. Rudavskii and V. I. Kondratenko, Zhur. obshchei Khim., 1971,41,2398. A. D. Gordeev, I. A. Kyuntsel, G. A. Golik, and V. A. Shokol, Zhur. obshchei Khim., 1973, 43, 9. H. Teichmann and M. Jatkowskii, J. prakt. Chem., 1972, 314, 118, 125. J. P. Berry, A. F. Isbell, and G. Hunt, J. Org. Chem., 1972, 37, 4396. A. F. Isbell, J. P. Berry, and L. W. Tansey, J. Urg. Chem., 1972, 37, 4399.

128

Organophosphorus Chemistry

gave optically active a-aminophosphonic In attempts to condense N-protected a-aminophosphonic acids with free amino-groups as a route to peptide analogues, it was found that DCC was unsatisfactory.66Instead it was necessary to prepare the protected phosphorochloridate esters (72) to activate the phosphoryl group. A convenient route to o-aminophenylphosphonic acid involves reaction of the o-bromo-acid with cuprous bromide followed by ammonia.67 ROPCIZ

HF

E: I

~ ~ 0 'RO-P=O

1 H (73)

Monoalkyl esters of phosphonofluoridic acid (73) (which exist exclusively in the Pv form) have been obtained by reaction of monoalkyl phosphonodichloridites with hydrogen fluoride and water in ethereal A new route to phosphonic acid dichlorides involves reaction of the P=S analogues with thionyl chloride,ss but is naturally limited to those cases where the latter are the more readily available. Alka-l,3-dienylphosphonothioicdichlorides (74)

ii, H,S

CHZPSClz

CHPSCIZ

may be obtained from the adducts of 1,3-dienes (e.g. isoprene) with phosphorus pentachloride by treatment first with hydrogen sulphide and then with triethyla~nine.~~ The furan derivative (75) was formed by bromine oxidation of the readily available dihydro-compound (76).71

66

'7

60

'0

1'

W. F. Gilmore and H. A. McBride, J. Amer. Chem. SOC.,1972,94,4361. K. Yamauchi, M. Kinoshita, and M. Imoto, Bull. Chem. SOC.Japan, 1972,45,2528. A. M. Lukin, N. A. Bolotina, and G. B. Zavarikhina, Merody. Poluch. Khim. Reactiv. Prep., 1970, 11 (Chem. Abs., 1972,76, 140963). U. Ahrens and H. Falius, Chem. Ber., 1972,105, 3317. L. Maier, Helv. Chim. Acta, 1973, 56, 492. L. N. Mashlyakovskii, T. A. Zagudaeva, B. I. Ionin, I. S. Okhrimenko, and A. A. Petrov, Zhur. obshchei Khim., 1972, 42, 2648. S. V. Fridland, V. P. Shostak, and G. K. Kamai, Zhur. obshchei Khim., 1972, 42, 121.

129

Quinquevalent Phosphorus Acids CIHpC CIHpC

0 0

0 Me MEteh hTT- - t$ -- O M ee

& basc

jP/ / \

/\

R

R' 'OMe OMe

a@-Epoxyalkyl-phosphonic and -phosphinic acid esters (77) may be prepared by a Darzens-type condensation of a-chloromethylphosphonateesters with

s

S

R--P

/s \IIP-R + II \s' S

s

II I F

PhPF,

R-P-S-P-R

(81)

II I F

(82)

s s (RO) zP--P(OR)

II I1

2

S , (RO) P-P(0R)

(84)

(83)

Two new routes to symmetrical trithio-pyrophosphonicacid derivatives (78) have been reported. The fist employs73reaction of the phosphinothioate ester (79) with the sulphenyl chloride (80)and is similar to the route adopted earlier for symmetrical pyrophosphorothioates. The second, which is probably more limited, involves reaction of phenyltetrafiuorophosphorane with the perthiophosphinic anhydride (81) to give (82).74 It was shown in this last case that the product consisted of a 1 : 1 mixture of dl- and meso-forms. A novel dithio-hypophosphonate ester (84) was formed when (83) was treated with sulphur; with oxygen, (83) gave only products containing a P-0-P link.76 Pyrolysis of the diphosphonic acid (85) at 330-370 "Cgives the expected

(85) 7'

74 76

(86 )

(8 7)

I. A. Dormidonov, V. F. Martynov, and V. E. Timofeev, Zhur. obshchei Khim., 1972, 42, 479. L. Almasi, N. Popovici, and A. Hantz, Montash., 1972, 103, 1027. R. K. Harris, J. R. Woplin, M. Murray, and R. Schmutzler, J.C.S. Dalton, 1972, 1590. M. V. Proskurnina, A. L. Chekhun, and I. F. Lutsenko, Zhur. obshchei Khim., 1973, 43, 66.

130

Organophosphorus Chemistry

(86), together with a large amount of the cyclodephosphorylated acid (87).76 In view of the marked reluctance to closure of seven-membered rings in comparison with six-membered rings, this result appears unusual. SolvoIyses of Phosphonic and Phosphinic Esters.-The first kinetic evidence for the involvement of an intermediate - presumed to be quinque covalent - in This was observed the solvolysis of a Pv acid derivative has been rep~rted.~' in the base solvolysis of methyl di-isopropylphosphinate, which shows an induction period and whose rate of hydrolysis is consistent with reversible formation of an intermediate which then undergoes breakdown (Scheme 6)

Scheme 6

with k,N" k, N" 0.1 k-,. Additional, but less unequivocal, evidence for the intervention of such intermediates in other phosphinic esters was claimed from studies on the rates of base hydrolysis of a series of esters of diphenylphosphinic acid, which have p* 8 (carboxylic esters have p* 11) - larger than would be expected if the rate-determining step were hydroxide attack. None of these esters showed l*O exchange with solvent, but this is quite consistent with the unfavourable pseudorotations necessary in the intermediate. Investigations into the rates of acid-catalysed hydrolysis of methyl esters of several phosphinic show that although polar and steric effects are much less important than in the hydroxide reaction they are nevertheless considerably larger than those for comparable carboxylic esters. At high acid concentrations the catalytic rates diminish, presumably by reduction of the activity of the water. MePO(OAr), N

N

'

(88)

Solvolysis of the diary1 esters of methylphosphonicacid (88) in the presence of amines proceeds by general base catalysis.7BEven unhindered amines such as ammonia or aziridine gave no evidence of nucleophilic attack nor was any enhanced rate observed with hydrazine. Fluoride ion and several oxyanions were found to react by nucleophilic attack and, in the absence of any more satisfactory explanation, the preference for a general base mechanism with amines was set down to steric crowding in the transition state for nucleophilic attack. C. N. Robinson and W. A. Pettit, Tetrahedron Letters, 1972, 4977. R. D. Cook, P. C. Turley, C. E. Diebert, A. H. Fierman, and P. Haake, J. Amer. 1972,94,9260. Chem. SOC., R. D. Cook and K. Abbas, Tetrahedron Letters, 1973, 519. I @ H. J. Brass and M. L. Bender, J. Amer. Chem. SOC.,1972,94, 7421. 7'

'I7

Quinquevalent Phosphorus Acids

131

The enhanced hydrolysis rate of the ester (89) under acidic conditions (the neighbouring amide group having little effect under basic conditions) is attributed, by analogy with compounds with an o-carboxy-group, to intramolecular nucleophilic catalysis.s0 However, this view is reinforced by the observation that the loss of the second ester group is much faster than that of the first, which strongly suggests the cyclic ester (90) as an intermediate. Other examples of intramolecular nucleophilic catalysis have been reported from studies of solvolysis rates of several phosphorylated hydroxamic acids (91).81It was found that, unlike attack by an external nucleophile, the rates

HON=CA~ (91)

(92)

X = S, CH2, C0,or SO,

of these intramolecularreactions were relatively insensitive to steric hindrance. A somewhat unusual form of intramolecular nucleophilic catalysis may operate in the hydrolysis of some of the cylic phosphinates (92).82 When X = CO the rate was 100 times faster than when X = CH,; there was also a substantial increase in rate when X = SO,. Although part of these increases is probably due to electronic effects and angle strain it seems possible that, with X = COYhydration of the carbonyl group may be followed by intramolecular nucleophilic attack on phosphorus. Solvolysis of 2-chloro-l-hydroxyethyldiphosphonicacid proceeds rapidly in base with loss of chloride ion to give the rearranged diphosphonic acid CH,CIC(PO,H,),

I

OH

'0

base, H,O,PCH,COPO,H, (93)

0 /\ CH,-C(PO,H,),

OH 1 /R1 ArP-C,

(94)

0 OH

11

1 R2

R. Kluger and J. L. W. Chan, J. Amer. Chem. SOC.,1973, 95, 2362. J. I. G. Cadogan and D. T. Eastlick, J.C.S. Chem. Comm., 1973, 238. R. D. Cook and H. K. Norrish, Tetrahedron Letters, 1973, 521.

132

Organophosphorus Chemistry

(93).83A detailed kinetic analysis was not attempted owing to the fact that the various anionic species rearranged at different rates, but it was suggested that the epoxide (94) might be an intermediate. There seem no grounds on current evidence for preferring such a mechanism over a simple 1 ,Zmigration of phosphorus. Thermographic and conductimetric methods have been used to investigate the rearrangement of a-hydroxyalkylphosphinic acids (95) to pho~phonates.~~ It appears that the reaction proceeds by initial ionization of the alcoholic hydroxy-group and that when R1 and R2are electron-withdrawing, attack on phosphorus occurs to give the rearranged product; when R1and R2are electron-donating or weakly electron-attracting,fragmentation to the ketone and arylphosphinic acid is favoured.

(96)

The expected amide is produced when (96) is solvolysed with a primary amine as nucleophile, but when the solvolysis is carried out with an alcohol or secondary amine, 85 pyrrolidine-2-thione is formed. This intriguing difference in behaviour merits further investigation. Reactions of Phosphonic and Phosphinic Acid Derivatives.-Dimethyl sulphoxide reacts with phosphonochloridates with elimination of chloride, but the nature of the intermediates involved is not at all clear. Thus when (97) is allowed to react with DMSO (1 mole) in dichloromethane, and then treated with methanol, a good yield of methyl phenylphosphonate is obtained.86 With excess DMSO, (97) is converted into the phenylphosphonic acid, RPOClz \M:g(

- i,

DMSO ( I mole) ii,MeOH

/O

* R-pToH OMe

(excess)

ROP0,H2

although it is very probable that pyrophosphonates are formed, at least as intermediates. In contrast, the P=S analogues are converted first to the P=O compounds with loss of sulphur and dimethyl sulphide, the reaction possibly following the route shown (Scheme 7).87

O6

0. T. Quimby, W. A. Cilley, J. B. Prentice, and D. A. Nicholson, J. Org. Chem., 1973, 38, 1867. A. N. Pudovik, I. V. Konovalova, G. V. Romanov, R. G. Fitseva, and N. P. Burmistrova, Zhur. obshchei Khim., 1973, 43, 41. L. V. Razvodovskaya, A. F. Grapov, and N. N. Melnikov, Zhur. obshchei Khim., 1972, 42, 1277. R. J. Brooks and C. A. Bunton, J. Org. Chem., 1973, 38, 1614. M. A. Ruveda, E. N. Zerba, and E. M. deMoutier Aldao, Tetrahedron 1973, 29, 585.

Quinquevalent Phosphorus Acids

133

RPOC12

-+

+

Me,S=S

/ Me,S

+S

Scheme 7

Contrary to some earlier reports, acidic hydrolysis of some ag-unsaturated phosphonic acid esters (98) results not merely in loss of the ester groups but in concomitant dephosphorylation.88 The saturated acid [from borohydride

R1

CN

(99)

reduction of (98)] was found to behave similarly. Under basic conditions the related ester types (99) may undergo retro-aldol or Wittig-type reactions, the proportion following each pathway being dependent on the substitution pattern and conditions of reaction.89

\s 4

L

P

" R

s

P

N"R3 SiMe,

(102)

Further studies of the reactions of perthiophosphinicanhydrides (100) have appeared. The cycloaddition products formed from these and a series of unsymmetrically substituted 1,3-dienes suggest that a two-stage mechanism is It was proposed that the initial addition was such as to give the more stable biradical species; however, there is as yet no clear evidence of the intervention of radicals in this reaction. Compound (100) also undergoes novel cycloaddition reactions with alkynamines to give (101),91whereas with am Dl

C. N. Robinson, P. K. Li, and J. F. Addison. J. Org. Chem., 1972,37,2939. D. Danion and R. Carrie, Tetrahedron, 1972, 28, 4223. A. Ecker, I. Boie, and U. Schmidt, Monatsh., 1973, 104, 503. N. Schindler and W. Ploger, Synthesis, 1972, 421.

134

Organophosphorus Chemistry

trimethylsilyl azide m unusual replacement reaction (claimed to be quantitative) occurs to give (102).9a

(103)

The thiophosphonamide ester (103) is hydrolysed by acid with loss of the ester group rather than P-N cleavageg3and is doubtless a consequence of the low basicity of the nitrogen in this compound. Methylation of (103) with methyl iodide and sodium hydroxide gives exclusively S-methylation (and subsequent loss of methanethiol), whereas diazomethane gives a mixture of Nand S-methylated products. Oxidation of the ester (104) with rn-chloroperbenzoic acid has been shown to give the disulphide ester (105) and not the

Et

0

I\

‘GJ

EtO’

\SPh 0

(106)

sulphoxide (106) previously Formation of (105) is explicable if it is assumed that the initial step is epoxidation of the P=S bond (see earlier) followed by rearrangement of the intermediate. It has been shown that the stereochemistry of reactions of the series of phosphonate esters (107) with phenylmagnesium bromide is dependent on the nature of the leaving group.g6With X = F, inversion of configuration occurs, whereas with X = SMe, retention is observed. When X = CI the reaction proPr’O, &O P / \. Me X (107)

’’ H. W. Roesky and M. Dietl, Angew. Chem. Internat. Edn., 1973, 13,425. *a

L. Almasi, N. Popovici, and I. Zsak6, Chem. Ber., 1973, 106, 1384. R. Fukuto, Life Sci., 1972, 11, 583 (Chem. Abs., 1972, 77, 74984). G. R. Van den Berg, D. H. J. M. Platenberg, and H. P. Benschop, Rec. Trav. chim., 1972, 91, 929.

*‘ D. A. Wustner, J. Dermarchelier, and T. O6

135

Quinquevalent Phosphorus Acids

ceeds with predominant inversion, but this result is more equivocal since it was found that small amounts of the Grignard reagent catalysed racemization of the substrate. The retention with X = SMe was explained on the basis that initial attack gave a bipyramidal intermediate in which the alkoxy-group was apical and that a pseudorotation was necessary to bring this to the conformation required for thiolate to be lost. The nitration of some arylphosphonic acids has been examined.QsPhenylphosphonic acid gave principally m-substitution (80 %) along with o-substitution (20 %), the rate of reaction increasing in aprotic solvents. With substituted aryl acids it was found that the rate increased with increasing pKa of the starting acid, indicating that the free acid rather than the protonated form is involved. Rather surprisingly, the arsenic analogues reacted more slowly but this may well be due to formation of relatively stable and unreactive cationic arsenic species. ArCN,PO(OR)

ArSo 2N3

p - 0 iNCGH4CHiPO(OR)2

a-Diazoalkyl-phosphonic and -phosphinic acid derivatives (108) continue to attract attention. The most general route to these compounds would seem to be reaction of the accessible a-keto-phosphonates with toluene-p-sulphony1 hydrazide followed by base:7 but diazo-group transfer from toluene-psulphonyl azide may be possible when the CH protons are sufficiently acidic as in (109).Q8Reactions of the phosphonylcarbenes formed by irradiation of these diazo-compounds have been further inve~tigated.~~ For the thermal cycloaddition of (108) to olefins it was observed that electron-withdrawing substituents on the aryl ring decreased the rate of reaction, implying that the addition is predominantly nucleophilic in character. However, the p-value for this last reaction was small and steric effects may therefore be more important. Dimethyl a-diazomethylphosphonate reacts with enamines to give (1lO),gQwhereas with cyclic 1,Zdiketones addition may be followed by rearrangement (with loss of nitrogen) to give ring-expanded products (1 1l)?OO 0

R2

RIiN

R-

+ (MeOM':

CHN,

-

(Me0)2P-CN2CH-CHR22

II

0

I

NR'Z

T. A. Modro and A. Piekos, Tetrahedron, 1972, 28, 3867. H. Scherer, A. Hartmann, M. Regitz, B. D. Tunggal, and H. Giinther, Chern. Ber., 1972, 105, 3357. N. Gurudata, C. Benezra, and H. Cohen, Cunad. J. Chem., 1973,51, 1142. W. Welter and M. Regitz, Tetrahedron Letters, 1972, 3799. M. Regitz, M. R. W. Disteldorf, U. Eckstein, and B. Weber, Tetrahedron Letters, 1972, 3979.

136

Organophosphorus Chemistry

do ' L ! L F o -m. CHN,PO(OR),

H

OH

y,0CH,CHMe2 CIICP, OCH,CHMe, (112)

CI,Cb-OCH,kMe,

I

OH

I

--+Cl,CP=O

I

OCH,CHMe,

OCH,CHMe,

+>

Irradiation of the ester (112) appears to result in y-hydrogen abstraction and resultant Norrish type I1 cleavage of the biradical;lo1the stability of the corresponding dimethyl ester to irradiation is explicable on this view. The CMe, I

(114)

(1 13)

unsaturated cyclic phosphinate (1 13) is converted into (1 14) on irradiation in the presence of oxygen.1o2

Base-catalysed condensation of the phosphonate (115) with aldehydes leads to (116) and not (117).lo3The cyclic phosphonate (118) undergoes a novel 0

I/

R CH=CH PCH ,PO(OEt)

I

OEt (1 17) lol lo*

Y. Ogata, Y. Izawa, and T. Ukigai, Bull. Chem. SOC.Japan, 1973,46, 1009. K. Dimroth, A. Chatzidakis, and 0. Schaffer, Angew. Chem., Internat. Edn., 1972, 11, 506.

lo*

W. F. Gilmore and J. W. Huber, tert., J. Org. Chem., 1973, 38, 1423.

137

Quinquevalent Phosphorus Acids

condensation with benzonitrile under strongly basic conditions, forming the ring-expanded product (119).1°*

-b:. P

O4 'OEt (1 19)

Using n.m.r. it has been possible to assign the stereochemistry of the phosphonates (120) resulting from addition of secondary arnines to ethynyl-

( 120)

phosphonates.lo6The allenephosphonic ester (121) undergoes cycloaddition with diphenyldiazomethaneto give a mixture of (122) and (123) when R = H but when the 1-position is substituted (R = Ph), methylenecyclopropane

(121)

(122)

Ph&O(OEl),

Ph

Ph

CN

0

CH,,

PO(OEth (125)

NH2nA

1 , PO(0Et)p

ArCrNLO-

' d

(127)

F. Mathey and J.-P.Lampin, Tetrahedron Letters, 1972, 1949. lD6 M. S. Chattha and A. M. Aguiar, J. Org. Chem., 1973, 38, 820.

lo'

0rganophosphorus Chemistry

138

derivatives (124) are major products.106 Diethyl cyanomethylphosphonate (125) adds to aryl azides and nitrile oxides to form triazoles (126) and oxazoles (127), respe~tive1y.l~~ N(CH,PO,H,),

PasL '

N(CH2CI)Ll

(1 25)

The triphosphonic acid (128) is dephosphonylated by reaction with phosphorus pentachloridelo8 but can be esterified with orthoformate esters. Phosphorus pentasulphide converts the cyclic anhydride (129) into (130), from which triphenylphosphine removes sulphur to give (13 1).loS

Miscellaneous.-The effect of branching of the alkyl chain in a series of dialkylphosphonic acids and the related phosphine oxides is to decrease both the acidity of the former and the basicity of the latter, which effect is attributed to poorer solvation of the ions formed.llO In contrast, it seems probable that electronic effects increase the acidity and decrease the basicity of analogous phosphetan derivatives. It has been found that the basicity of the phosphinate esters (1 32) in sulphuricacid follows H Arather than Hobut, slightly disturbing, Ar-P,

4*

I OMc Me (132)

(1 33)

was the observation that the pKa values from lH n.m.r. shifts of the methyl and methoxy protons were not in agreement.lll The basicity of a series of dioxaphosphorinans (133) with varying R correlates with the Taft (T* value of R. In these compounds the P = O is preferentially equatorial except when R = Ph or NMe,.l12 A. N. Pudovik, N. G. Khusainova, and T. V. Timoshiva, Zhur. obshchei Khim., 1972, 42, 2159. U. Heep, Annalen, 1973, 578. lo8 L. Maier, Helv. Chim. Acta, 1973, 56, 1257. l o o M. A. Vasyanina and V. K. Khairullin, Zhur. obshchei Khim., 1972, 42, 2644. 110 A. G. Cook and G. W. Mason, J. Org. Chem., 1972, 37, 3342. ll1 R. Curci, A. Levi, V. Lucchini, and G . Scorrano, J.C.S. Perkin 11, 1973, 531. 11* J. P. Majoral, R. Pujol, and J. Navech, Bull. SOC.chim. France, 1972, 606. 11' C. M. Frey and J. E. Stuehr, J. Amer. Chem. SOC.,1972,94, 8898; C . M. Frey, J. L. Banyasz, and J. E. Stuehr, ibid., p. 9198.

Quinquevalent Phosphorus Acids

139

Stability constants and pKa values have been measured for the complexes formed by inorganic phosphate and a variety of nucleotide phosphates and polyphosphates with Mg2+ and Ni2+.l13It appears that Mg2+ complexes weakly and unspecifically with all of these phosphates whereas Nia+ shows some selectivity, which may reflect additional interactions with the rings. Crystal structure determinations on imidazolium dihydrogen phosphate give evidence of stacking interactions between the cations and also of a very strong hydrogen-bonding between the cation and the anion.114Hydrogen-bonding in dialkylphosphinodithioic acids and in the related ester (1 34) has been studied115 and, also, in the aziridinylphosphonic ester (135), where it slows the rate of N inversion.ll6

have been prepared from The radical ions Hfi02-, HfiO,-, and fi032reaction of hydroxyl radicals with hyphophosphorus and phosphorus acids. E.s.r. measurements indicate that there is significant delocalization of the unpaired electron spin in these radicals into the 3d orbitals on phosp h o r ~ Attempts ~ . ~ ~ ~to demonstrate the involvement of px-dx bonding in diamagnetic phosphorus compounds has produced conflicting results. Thus although 31P n.m.r. indicates the existence of such bonding in pyridyl-4-

phosphonic esters (136), u.v., i.r., and pKa measurements contradict this.118 The photoelectron spectra of both (137) and (138) have been examined, but this tool proved insufficiently sensitive to distinguish epimers.llg. It has been shown that the signs of rotation of monoesters of alkylphosphonothioic acids are correctly predicted by Brewsters rule.120A rule has also 114 116

117 118 ll0

*O

R. H.Blessing and E. L. McGandy, J. Amer. Chem. SOC.,1972, 94, 4034. R. R. Shagidullin, I. P. Lipatova, L. I. Vachugova, R. A. Cherkasov, and F. K. Khairutdinova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 847. S . Rengaraju and K. D. Berlin, J. Org. Chem., 1972, 37, 3304. A. L. J. Beckwith, Austral. J . Chem., 1972, 25, 1887. D. Redmore, J , Org. Chem., 1973, 38, 1306. W. J. Stec, W. E. Morgan, J. R. VanWazer, and W. G. Proctor, J. Inorg. Nuclear Chem., 1972,34, 1100. M. Mikolajczyk, J. Omelanczuk, and M. Para, Tetrahedron, 1972, 28, 3855.

OrganophosphorusChemistry

140

been given for correlating the sign of the Cotton effect of these compounds with the substitution pattern. Phenyl-l-naphthylphosphinothioicacid has been prepared and resolved by means of its quinine salt.121 Methylphosphonodifluoridate forms complexes with amines (primary amines react) in which the methyl protons appear as a doublet and the fluorines as a single resonance.122This suggests a rapid F exchange, which may occur by way of the bridged dimer (139). Lanthanide shift reagents have been used to assign the stereochemistry of the enol phosphates resulting from the Perkow reaction and the results discussed in terms of the mechanism of this rea~ti0n.l~~

(1 39)

(140)

There have been further n.m.r. studies on conformational questions in six-membered cyclic phosphates and phosphonate Also reported12sis the e.s.r. of the stable radical (140) from oxidation of the corresponding phosphoramidate with p-nitroperbenzoic acid. Calculations have been performed to determine the preferred conformation of the dimethyl phosphate anion.12n

V. A. Chauzov and I. F. Lutsenko, Zhur. obshchei Khim., 1973, 43, 69. R. L. Wintermyer, L. L. Szafraniec, and H. R. Bradford, J. Org. Chem., 1972, 37, 2355. l * a I. J. Borowitz, K. C. Yee, and R. K. Crouch, J . Org. Chem., 1973, 38, 1713. l a 4 J. A. Mosbo and J. G . Verkade, J. Amer. Chem. SOC., 1973, 95, 204. l a b T. D. Inch and G. J. Lewis, J.C.S. Chem. Comm., 1973, 310. K. Bergeson and T. Vikane, Acta Chem. Scand., 1972, 26, 1794. lX7 R. S. Edmundson, J.C.S. Perkin I , 1972, 1660. l a BD. Gagnaire, A. Rassat, J. B. Robert, and P. Ruelle, Tetrahedron Letters, 1972, 4449. l a S M. D. Newton, J. Amer. Chem. SOC.,1973, 95, 256.

lS1

lap

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

1 Introduction The amount of published work on biologically important phosphorus compounds has continued to increase at a prodigious rate during the past year. In the synthetic field, pride of place must go to Khorana’s synthesis1 of the structural gene of tRNAA1&from yeast, details of which, in thirteen successive papers, occupied an entire number of the Journal of Molecular Biology. As mentioned in last year’s Report, insolubilized mono- and polynucleotides have been used extensively in the purification by affinity chromatography of enzymes and nucleic acids, particularly those nucleic acids containing A-rich sequences.a Among the books on nucleic acids and nucleotides which have been published recently are a compilation of synthetic methods for polynucleotidesYsa review of techniques of nucleic acid fra~tionation,~ and a text on experiments with nucleic acids.6 2 Mono-, Oligo-, and Poly-nucleotides

Mononuc1eotides.-The phosphoryl chloride-phosphotriester method has been used to synthesize the 5’-phosphate esters of nucleosides, e.g. or-uridine ( 5-etho~ycarbonyluridine,~ puromycin 3’-peptide derivatives (2),* and

*

Abbreviations used in this Chapter may be found in the Instructions to Authors of the Biochemical Journal. H. G. Khorana, K. L. Agarwal, H. Biichi, M. H. Caruthers, N. K.Gupta, K. Kleppe, A. Kumar, E. Ohtsuka, U. L. RajBhandary, J. H. van de Sande, V. Sgaramella, T. Terao, H. Weber, and T. Yamada, J. MoI. Biol., 1972,72,209. * J. Delarco and G. Guroff, Biochem. Biophys. Res. Comm., 1972,49, 1233; U . Lindberg and T. Persson, European J , Biochem., 1972, 31,246; H. Nakazato and M. Edmonds, J. Biol. Chem., 1972, 247, 3365; J. R. Greenberg and R. P. Perry, J. Mol. Biol., 1972, 72, 91; C. H. Faust, jun., H. Diggelman, and B. Mach, Biochemistry, 1973, 12, 925; Y. Yogo and E. Wimmer, Nature New Biol., 1973,242, 171 ;C. R. Astell and M. Smith, Biochemistry, 1972, 11, 41 14. * G. R. Pettit, ‘Synthetic Nucleotides’, Van Nostrand Reinhold, New York, 1972, Vol. 1. S. R. Ayad, ‘Techniques of Nucleic Acid Fractionation’, Wiley, New York, 1972. ‘ J. H. Parish, ‘Principles and practice of experiments with nucleic acids’, Longmans, London, 1972. ’ A. Hol9, Coll. Czech. Chem. Comm., 1973,38, 100. A. Hol9, Coll. Czech. Chem. Comm., 1972,37, 1555. ’ R. J. Harris, J. F. B. Mercer, D. C. Skingle, and R. H. Symons, Canad. J. Biochem., 1972, 50, 918.

141

Organophosphorus Chemistry

142

NMe, I

(3)

(4)

virazole (l-~-D-ribofuranosy~-l,2,4-triazole-3-carboxamide) (3).g Virazole, an antiviral agent,lo is analogous to aminoimidazole carboxamide riboside (AICAR) (4), which is an intermediate in purine biosynthesis. The antiviral activity of virazole is, however, not reversed by AICAR or its 5’-phosphate, and it appears that the cause of the antiviral activity is the inhibition of GMP synthesis at a step involving the conversion of IMP to XMP. 2-Cyanoethyl phosphate and DCC have been used to prepare nucleotides from orotidine,ll 5-fluorouridine,12 and 2’-azido-2’-deoxyuridine (5).13 Nucleotides derived from (5) have been reduced to 2’-amino-2’-deoxyuridine derivatives. Other phosphorylating agents used in nucleotide synthesis are bis-(2,2,2-trichloroethyl) phosphorochloridate for both anomers of the

D. G. Streater, J. T. Witkowski, G. P. Khare, R. W. Sidwell, R. J. Bauer, R. K. Robins, and L. N. Simon, Proc. Nat. Acad. Sci. U.S.A., 1973,70,1174. l o J. T. Witkowski, R. K. Robins, R. W. Sidwell, and L. N. Simon, J. Medicin. Chem., 1972,15, 1150. l1 2.Kucerovi, A. Hal$, and R. W. Bald, Coll. Czech. Chem. Comm.,1972,37,2052. I’ J. M. Whiteley, J. Galivan, and I. Jerkunico, Fed. Proc., 1973, 32, 591Abs. D. Wagner, J. P. H. Verheyden, and J. G. Moffatt, J. Org. Chem., 1972, 37, 1876.

Phosphates and Phosphonates of Biochemical Interest

I43

ribonucleoside derived from 2(1H)-pyridone (6),14 and 32P-labelledpolyphosphoric acid for the preparation of 32P-labelled5’-ribonucleotides.15 Ester exchange between 4-nitrophenyl phosphate and 2’,3’-O-isopropylidene ribonucleosides in the presence of pyridine has been shown to be a good method for the synthesis of nucleotides.ls Ribonucleoside 5’-hydroxyalkanephosphonates (7), which are prepared from the 2’,3’-O-protected nucleosides,

NN-carbonylbisimidazole,and the hydroxyalkanephosphonic acid, are good substrates for snake venom 5’-nucleotidase, unlike the corresponding 5’-methanephosphonates.17Sulphonyl, phosphoryl, and acyl azides react with

phosphorous esters of nucleosides to give imidophosphates (8).18 The latter decompose readily to give the salt of the cyclonucleoside. Many papers have been published during the past year on the chemistry and biochemistry of cyclic nucleotides, including two reviews on cAMP.l9,2o More evidence is appearing on the role of cGMP as a second messenger, and for example it has been postulated21 that cGMP is involved in mitosis in lymphocytes. Lack of a simple assay system for cGMP has hindered work on this compound but this now seems to have been overcome.2zA new assay for cAMP involving a specific binding protein attached to Sepharose has been Derivatives of cAMP require a free 2’-hydroxy-group for maximum activation of beef brain and beef heart protein k i n a ~ e s as ,~~ 2’-O-esters and l6

l7

ao 91

ga g4

U. Sequin and C. Tamm, Helv. Chim. Acta, 1972,55, 1196. F. R. Zuleski and E. T. McGuinness, Analyt. Biochem., 1972, 47, 315. T. Hata and K. J. Chong, Bull. Chem. SOC.Japan, 1972,45, 654. A. Holf and N. D. Hong, Coll. Czech. Chem. Comm., 1972, 37,2066. G. Baschang and V. Kvita, Angew. Chem. Internat. Edn., 1973, 12, 70. I. Pastan, Sci. Amer., 1972, 227, 97. W. Y . Cheung, Perspect. Biol. Med., 1972, 15, 221. J. W. Hadden, E. M. Hadden, M. K. Haddox, and N. D. Goldberg, Proc. Nut. Acad. Sci. U.S.A., 1972, 69, 3024. G. Schultz, J. G. Hardman, K. Schultz, J. W. Davis, and E. W. Sutherland, Proc. Nut. Acad. Sci. U.S.A., 1973, 70, 1721. H. U. Frisch, V. Pligka, and R. Schwyzer, European J. Biochem., 1972,30, 1. J. P. Miller, D. A. Shuman, M. B. Scholten, M. K. Dimmitt, C. M. Stewart, T. A. Khwaja, R. K. Robins, and L. N. Simon, Biochemistry, 1972, 12, 1010.

Organophosphorus Chemistry

144

ethers of cAMP are less active than free CAMP. 2’-Deoxy-cAMP and ara.cAMP modified at the 2’-position are hydrolysed by cAMP phosphodiesterase more slowly than cAMP itself; on the other hand, analogues modified at the 6-position (e.g. 6-alkylthio-CAMPS)are cleaved by this enzyme more readily than the parent compound.25Analogues of cAMP modified in the 1- and 2-p0sitions,~~ phosphoramidates (9; X = NR),27 and thiophosThymiphates (9; X = S)27have been synthesized, as well as 4’-thio-~AMP.~~ dine 3’,5’-cyclic phosphate has been obtained by oxidation of the 3’,5’-cyclic ph~sphite.~~

X=P-0 mI q

AOHd e

O=P-0 O? I QAde

OH

I

I

NMe,

OH

(9)

(10)

NHCOtEt

EtOZCH N& ,

as

*‘ 8B

ao

‘Y

R. B. Meyer, D. A. Shuman, R. K. Robins, R. J. Bauer, M. K. Dimmitt, and L. N. Simon, Biochemistry, 1972, 11, 2704. B. Jastorff and W. Freist, Angew. Chem. Internat. Edn., 1972, 11, 713. B. Jastorff and T. Krebs, Chem. Ber., 1972, 105, 3192. R. B. Meyer, jun., D. A. Shuman, and R. K. Robins, Tetrahedron Letters, 1973, 269. A. K. M. Anisuzzaman, W. C. Lake, and R. L. Whistler, Biochemistry, 1973,12, 2041. G. Baschnng and V. Kvita, Angew. Chem. Internat. Edn., 1973,12,71.

Phosphates and Phosphonates of Biochemical Interest

145

The modification of adenine and cytosine nucleotides with cc-halogenoaldehydes31gives fluorescent products which should be of use as probes to determine enzyme conformation ; fluorescent CAMP,^^ ADP,33 A TP,33 FAD:* and NAD+35 have been prepared. Polymerization of 1,N6-etheno-ADP (cADP) (ll), the product obtained from chloroacetaldehyde and ADP, with polynucleotide phosphorylase leads to p o l y ( ~ A )Treatment .~~ of poly(A) with chloroacetaldehyde leads to a polymer containing varying amounts of &A residue^.^' Phosphorolysis of poly(EA) by polynucleotide phosphorylase has been monitored by fluorescence spe~troscopy,~~ and the binding of ATP to aspartate transcarbamylase has been studied by similar Although EATP is inactive as a substrate for fkefly luciferase, chemically synthesized luciferyl-CAMP (12) is oxidized by luciferase with the emission of red light, in contrast to the yellow-green emission observed with I~ciferyl-AMP.~~ The change in colour of the emitted light may be due to a change in the protonation of the luciferyl nucleotide. Diethyl pyrocarbonate (13) destroys the infectivity of single-stranded viral RNA by modifying adenine residues when the imidazole ring is cleaved to give (14).40Dinucleoside phosphates derived by the action of (13) on ApU or UpA are digested appreciably more slowly by ribonucleases and phosphodiesterases than the parent compounds, and derivatives from ApA are not attacked at all. It has been suggested that (13) may be a useful tool for detecting exposed A-residues in nucleic acids. The aminecatalysed elimination of the terminal nucleoside from RNA following periodate oxidation, which was mentioned in last year’s Report, has been re-e~amined.~~ The new data do not agree with an earlier proposal4* for the mechanism of this reaction. After the 3’-terminal nucleotide has been eliminated, further oxidation by periodate is required before the free base is eliminated and two equivalents of formic acid are Cleavage of the C-4‘--OC-l’ bond is thought to take place. A possible reaction sequence for N. K. Kochetkov, V. N. Shibaev, and A. A. Kost, Doklady Akad. Nauk S.S.S.R., 1972, 205, 100 (Chem. Abs., 1972,77, 126 991). a * J. A. Secrist, tert., J. R. Barrio, N. J. Leonard, C. Villar-Palasi, and A. G. Gilman, Science, 1972, 177, 279. a8 J. A. Secrist, tert., J. R. Barrio, N. J. Leonard, and G. Weber, Biochemistry, 1972, 11, 3499. 8‘ J. R. Barrio, G. L. Tolman, N. J. Leonard, R. D. Spencer, and G. Weber, Proc. Nat. Acad. Sci. U.S.A., 1973, 70, 941. ab J. R. Barrio, J. A. Secrist, tert., and N. J. Leonard, Proc. Nat. Acad. Sci. U.S.A., 1972, 69, 2039. aE H. Lerach and K. H. Scheit, Biochim. Biophys. Acta, 1973,308,28. R. F. Steiner, W. Kinnier, A. Lunasin, and J. Delac, Biochim. Biophys. Acta, 1973,294, 24. Y. H. Chien and G. Weber, Biochem. Biophys. Res. Comm., 1973,50,538. I@ M. De Luca, N. J. Leonard, B. J. Gates, and W. D. McElroy, Proc. Nat. Acad. Sci. U.S.A., 1973, 70, 1664. 40 N. J. Leonard, J. J. McDonald, R. E. L. Henderson, and M. E. Reichmann, Biochemistry, 1971, 10, 3335; R. E. L. Henderson, L. H. Kirkegaard, and N. J. Leonard, Biochim. Biophys. Acta, 1973,294, 356. ‘l M. Uziel, Biochemistry, 1973, 12, 938. 4 a D . H. Rammler, Biochemistry, 1971, 10, 4699. 81

146

Organophosphorus Chemistry

HC0,H

+ Ade-CHO

*

Adenine

+ HC0,H

Scheme 1 the degradation of AMP is shown in Scheme 1. The sensitivity of this methcd of sequential analysis of RNA has been improved43by the introduction of tritium into the terminal nucleoside fragment after the latter has been released from the polynucleotide chain. This is achieved by reduction of the dialdehyde chain

I

chain

O=P-OH 0

I

O=P- OH 0

VYB

NaBf4+

OHC

vy

HOH,C

H,OH

CHO

(15)

(15) with tritiated borohydride after excess periodate has been removed from

the reaction mixture by the addition of rhamnose. The stereochemistry of the transesterification step of ribonuclease TIhas been shown to proceed by am in-line mechanism with the aid of the two diastereoisomers of guanosine 2’,3’-cyclophosphothioate (16) and (17).44

D. E. Schwartz and P. T. Gilham, J . Amer. Chem. SOC., 1972,94, 8921.

‘‘ F. Eckstein, H. H. Schulz, H. Ruterjans, W. Haar, and W. Maurer, Biochemistry, 1972, 11, 3507.

Phosphates and Phosphonates of Biochemical Interest

147

The mixture of stereoisomers could not be separated, but their 31Pn.m.r. chemical shifts were identical with the endo- and exo-isomers of the known uridine 2’,3’-cyclophosphorothioate.45Only the endo-isomer (1 7) is hydrolysed by RNase TI without loss of sulphur, the resistant exo-isomer being a competitive inhibitor for the enzyme.44Moreover, only the endo-isomer reacts with methanol in the presence of RNase TI to give the O-methyl ester of guanosine 3’-phosphorothioate, thus suggesting the in-line mechanism. 3’-a-Naphthyl nucleotide esters have been proposed as nuclease substrates for the cytochemical detection of these enzymes;46the a-naphthol which is released during the enzymic hydrolysis is detected by coupling with an azo-dye. A cytochemical substrate for phosphodiesterase I1 is thymidine 3’-(5-bromo4-chloroindol-3-yl) phosphate (1 8).47 Aerobic oxidation of 5-bromo-4-

(19)

chloroind-3-01liberated by the enzyme leads to the highly coloured indigo (1 9). The importance of the 2’-hydroxy-group in the binding of substrates to RNase A is underlined in a study of the inhibition of this RNase with ara.nucleotide~.~~ The association constant of ara.-3’-CMP is five-fold greater than that of 3’-CMP and ara.-cytidine itself is a good inhibitor of the enzyme. The 2’-hydroxy-group in ara-nucleotides, which are in the anti-conformation, hinders rotation of the pyrimidine ring about the glycosidic bond. It is suggested that the relative rigidity of the ma.-nucleosides may favour their binding to the enzyme, though it is difficult to see why this should have such a pronounced effect on the association constants. F. Eckstein, J . Amer. Chem. SOC.,1970,92,4718. R. Kole, H. Sierakowska, and D. Shugar, Biochim. Biophys. Acta, 1972, 289, 323. ’’ J. P. Horwitz, C. V. Easwaran, and P. L. Wolf, Biochim. Biophys. Acta, 1972,276,206. 4 e D. R. Pollard and J. Nagyvary, Biochemistry, 1973, 12, 1063. 46

4s

148

OrganophosphorusChemistry

The 5’-phosphates of 2’,8-S-cycloadenosine (20; X = S)49 and 5’,8-cycloadenosine (21)50have been synthesized and examined as enzyme substrates. The hydrolysis of (20; X = S ) by phosphatases occurred generally more slowly

than that of AMP.49A mixture of stereoisomers of (21) was prepared which could not be separated but which could be detected by IH n.m.r. spectrocopy.^^ One of these isomers was a substrate for a number of AMP-requiring enzymes, e.g. AMP aminohydrolase and AMP kinase, indicating that AMP is in the anti-conformation when bound to these enzymes. Evaporation of dilute solutions of uridine and ammonium oxalate in contact with apatite under relatively mild conditions leads to the synthesis of uridine phosphate^.^^ Phosphoryl transfer does not take place if oxalate is omitted from the reaction; on the other hand, addition of low concentrations of condensing agents such as cyanamide or imidazole substantially increases the yield of uridine nucleotides. Doubt has been cast on the role of apatite in prebiotic phosphorylation by a reportK2that struvite (MgNH4P0,,6H,O) rather than apatite is precipitated when phosphate is added to sea water containing more than 0.1M ammonium ion. When struvite is heated with urea in the presence of nucleotides, phosphoryl transfer takes place. The non-enzymic synthesis of oligoadenylates on templates lacking in steric regularity, e.g. poly-(l-vinyluracil), shows that there are little or no structural requirements for this template-directed reaction,Ksan observation which may have a bearing on the synthesis of polynucleotides under prebiotic conditions. An investigation of the thermodynamics of the interaction of bivalent metal ions with inorganic and nucleoside phosphates shows that magnesium behaves similarly with molecules which contain the same number of phosphoryl residues.54This must mean that there is little or no interaction between magnesium ions and the heterocyclic rings of nucleotides. Lactic and alcohol dehydrogenaseshave been purified by affinity chromatography using AMP bound to Sepharose through a six-carbon spacer attached M. Ikehara and S. Uesugi, Tetrahedron, 1972, 28, 3687. A. Hampton, P. J. Harper, and T. Sasaki, Biochemistry, 1972, 11, 4965. I1 A. W. Schwartz, Biochim. Biophys. A d a , 1972, 281, 477. G. J. Handschuh and L. E. Orgel, Science, 1973, 179,483. 6* P. M. Pitha and J. Pitha, Nature New Biol., 1972, 240, 78. C. M. Frey and J. E. Stuehr, J. Amer. Chem. SOC.,1972,94, 8898.

48

Phosphates and Phosphoiiates of Biochemical Interest

149

to the 6-position of the adenine ring.55Thymidylate synthetasessa and galactosyl tran~ferase~~* have been purified by chromatography using columns consisting of uridine nucleotides attached to Sepharose by a similar spacer. The y-phosphoryl group of dATP has been attached to cyanogen bromideactivated Sepharose by conversion into the y-(4-aminophenyl) ester (22):’a and an affinity column of this material has been used to purify ribonucleotide reductase from bacteriophageT4. Ribonucleotidereductase from Lactobacillus Zeichmanii has also been purified by affinity chromatography. In this instance a column of 5’-deoxyadenosylcobalamin-agarose was used in which the cobalamin was joined to the support through a carboxylic acid group linked to a twelve-carbon By a similar technique, the phosphodiesterase from Bothrops atrox venom has been purified using a column of Sepharose-bound 0-(4aminophenyl)-O’-phenylthiophosphate (23).68An alternative method of

linking ribonucleotides to insoluble supports is through the sugar residue. Oxidation of ribonucleotides with periodate gives the 2’,3’-dialdehyde, which which will react with an amino-substituted Sepharose to form insoluble derivatives (24).69This type of insolubilized nucleotide can be used to isolate

enzymes, e.g. meromyosin,60which will bind to both the heterocyclic ring and the phosphoryl residue(s) of the nucleotide. Nucleoside Po1yphosphates.-A number of ATP analogues have been synthe66

68

ao

H. Guilford, P. 0. Larsson, and K. Mosbach, Chem. Scripta, 1972,2,165; R. Ohlsson, P. Brodelius, and K. Mosbach, F.E.B.S. Letters, 1972,25,234. (a) P. V. Dannenberg, R. J. Langenbach, and C. Heidelberger, Biochem. Biophys. Res. Comm., 1972, 49, 1029; (b) R. W. Barker, K. W. Olsen, J. H. Shaper, and R. L. Hill, J. Biol. Chem., 1972, 247, 7135. (a) 0. Berglund and F. Eckstein, European J. Biochem., 1972,28,492; (b) R. H. Yamada and H. P. C. Hogenkamp, J. B i d . Chem., 1972,247,6266. A. Frischauf and F. Eckstein, European J. Biochem., 1973, 32,479. E. A. Wider de Xifra, S. Mendiara, and A. M. del C. Battle, F.E.B.S. Letters, 1972, 27, 275. R. Lamed, Y. Levin, and A. Oplatka, Biochim. Biophys. Acta, 1973, 305, 163. F

150

Organophosphorus Chemistry

sizeds1from the nucleoside monophosphates and pyrophosphoricacid with aid of NN-carbonylbisimidazole,and the same method has been useds2to prepare 3’-deoxynucleoside triphosphates, potential inhibitors of the final stage of (25) is a novel phosphoryRNA synthesis.P1-DiphenylP2-fluoropyrophosphate 0

II

0

(PhO)2P-O-P-F

II

I

000,

II II II + ADP * AdO--OPOPOP-F

I l l HO 0 OH

OH

H (25) (26) lating agent which has been employed for the synthesis of y-fluoro-ATP (26).63The transfer of radioactive phosphate from Y-[~~P]ATP to other nucleoside diphosphates with the aid of nucleoside diphosphate kinase has been proposede4aas a simple, rapid method for the preparation of ~-~~P-labelled nucleoside triphosphates as the enzyme is now commercially available. Other 32P-labellednucleoside triphosphates have been prepared chemically.64bThe transfer of the terminal thiophosphate residue from nucleoside 5’-0-(3thiophosphates) to nucleoside diphosphates is also catalysed by the k i n a ~ e . ~ ~ Analogues of ATP, e.g. (28), have been prepareds6by the action of 2’,3’-0-

0

It AdO--OP-CH I HO

0

0

P-CH

P-OH

II

-I,

HO

II

2-1

OH

isopropylideneadenosineon bis(dihydroxyphosphinylmethy1)phosphinate (27), and 5’-amino-Y-deoxyATP has been prepared from trimetaphosphate and 5’-amino-5’-deoxyadenosine. The zinc ion-catalysed phosphorylations7of 2-hydroxymethyl-1,lo-phenanthroline (29) by ATP is an interesting example of a model of a metallo-

CH20H (29) A. Gabbai, I. Marcus, J. G. Falbriard, and T. Posternak, Helu. Chim. Acta, 1971, 54, 2133. ‘I

a*

J. J. K. Novik and F. iorm, Coll. Czech. Chem. Comm., 1973,38,1173. B. Haley and R. G. Young, Biochemistry, 1972, 11, 2863. (a) R. W. Keenan, M. K. Zishka, and J. S. Nishimura, Analyt. Biochem., 1972,47,601; (b) D. P. Bloxham, M. G. Clark, P. C. Holland, and H. A. Lardy, Biochemistry, 1973,

12, 1596. R. S. Goody, F. Eckstein, and R. H. Schirmer, Biochim. Biophys. Acta, 1972,276,155. ” D. B. Trowbridge, D. M. Yamamoto, and G. L. Kenyon, J. Amer. Chem. SOC., 1972, 94, 3816. D. S. Sigman, G. M. Wahl, and D. J. Creighton, Biochemistry, 1972,11, 2236.

‘I

Phosphates and Phosphonates of Biochemical Interest

151

Ado

(30) (31) enzyme. The reaction is absolutely dependent on the metal ion and proceeds through a ternary complex, (30) or (31), consisting of ATP, (29), and a zinc ion. The last has three probable functions in the phosphoryl transfer, firstly to serve as a template on which both (29) and ATP can co-ordinate at the same time, secondly to alter the pKa of the alcohol so that it is an effective nucleophile at neutral pH, and finally to render the ATP more susceptible to nucleophilic attack. Terminal deoxynucleotidyl transferase from calf thymus requires transition-metal ions for activity and is competitivelyinhibited by l,lO-phenanthroline.s*This has led to the suggestions7that the catalytic function of the metal ions in this case is to interact with the 3’-hydroxy-group on the growing end of the deoxypolynucleotideand assist in the attack by this hydroxy-group on the terminal phosphate of the incoming nucleoside triphosphate. In contrast to these suggestions, 2,2’-bipyridyl stabilizes ATP towards copper-ion catalysed hydrolysi~.~~ Phosphoryl transfer from ATP to either water or inorganic phosphate in 30% aqueous polar solvents is catalysed by magnesium ions and requires the simultaneous presence of a dicarboxylic acid.70Although the function of the latter has not yet been determined, the solvent presumably acts as a hydrophobic cage which assists in bringing the reactants together. The hydrolysis of ATP, which is catalysed by diamines, proceeds with a high degree of specificity to ADP and orth~phosphate.~~ This may be another reaction in which ionic bonds are found with the a- and p-phosphoryl groups of ATP, leaving the y-phosphoryl group susceptible to attack. Guanylyl 3’,5’-dipyrophosphate (32) has been prepared enzymically from rH]GDP and Y-[~~P]ATP.’~ The 3H:32Pratio in (32) was unity, indicating

(32) Es ‘O

71

L. Chang and F. J. Bollum, Proc. Nut. Acad. Sci. U.S.A., 1970, 65, 1041. D. Buisson and H. Sigel, Angew. Chem. Internat. Edn., 1972, 11, 1025. N . Nelson and E. Racker, Biochemistry, 1973, 12, 563. S. Suzuki, T. Higashiyama, K. Ueda, and A. Nakahara, Bull. Chem. SOC.Japan, 1972, 45, 1579. J. Sy and F. Lipmann, Proc. Nut. Acad. Sci. U.S.A., 1973, 70, 306.

152

Organophosphorus Chemistry

that a pyrophosphoryl group had been inserted into the 3’-position of GDP. Although the biological function of (32) in protein synthesis has yet to be determined, it has been suggested that the formation of (32) is coupled to an initiation step in the protein synthesis.73 Oligo- and Poly-nuc1eotides.-As was mentioned in the Introduction, a double-stranded DNA molecule which could possibly act as a gene for tRNAAlafrom yeast has been synthesized by Khorana and his co-workers by a combination of chemical and enzymic rneth0ds.l For the the purposes of this synthesis, it was assumed that all base modifications take place once the tRNA has been synthesized in vivo and hence the base sequence in the gene would be complementary to the base sequence in a tRNA-like molecule which contained only A, G, C, and U. By chemical means, using DCC or triisopropylbenzenesulphonyl chloride to join monomeric deoxyribonucleotides, oligomers were synthesized7, which corresponded to fragments of both the plus and minus strands of the hypothetical gene. Hybridization of the correct oligomers gave short, double-stranded duplexes with single-stranded I

-i-GAGCAGGTGG-i

IIIIII

CCACC A-

CCGGACTCGT

I

TGAGCAGGTGGT

hybridize

IIIIII IIIIII

CCGGACTCGT CCACCA

J

(3 3)

i, phosphorylate ii, TI ligase

I

TGAGCAGGTGG-~

IIIIIIIIIIII

CCGGA CTCGTCCACCA

regions at the 3’- and 5’-ends (33). The 5’-hydroxy-groups were phosphorylated with the aid of polynucleotide kinase prior to the duplexes being joined by bacteriophage T4 ligase into larger segments (34).75 The correct base sequence within the larger segments is controlled by base pairing in the overlapping single-stranded regions of the small duplexes (33). The larger segments (34) were joined together to make the double-stranded gene by T4ligase, once the 5’-hydroxy-groups had been phosphorylated using polynucleotide The importance of T, ligase in the synthesis of oligo- and poly-deoxyribonucleotides has led to further investigations which have shown that the intramolecular joining of two strands of a duplex does not take place77and which D. L. Miller, M. Cashel, and H. Weissbach, Arch. Biochem. Biophys., 1973, 154, 675; E. Lund and N. 0. Kjeldgaard, European J . Biochem., 1972,28,316. 7‘ H. Weber and H. G. Khorana, J. Mol. Biol., 1972,72, 219, and subsequent papers. 7 s V. Sgaramella and H. G. Khorana, J . Mol. Biol., 1972, 72, 427, and subsequent papers. M. H. Caruthers, K. Kleppe, J. H. van de Sande, V. Sgaramella, K. L. Agarwal, H. Buchi, N. K. Gupta, A. Kumar, E. Ohtsuka, U. L. RajBhandary, T. Terao, H. Weber, T. Yamada, and H. G. Khorana, J . Mol. Biol., 1972, 72,475. ’’ V. Sgaramella and H. G. Khorana, J . MoI. Biol., 1972, 72, 493. 18

Phosphates and Phosphonates of Biochemical Interest

153

have also shown that oligothymidylates can be synthesized on a poly(dA) template by the Tdenzyme.78Alkyl phosphorothioates (35) have been used as phosphoryl-protecting groups to prevent the end-to-end joining of segments by T4ligase to give unwanted polymers.79When required, the S-alkyl groups can be removed by treatment with aqueous iodine.80 The role of ligase enzymes in repair processes in DNA has been mentioned in a recent review.81 Developments in the chemical synthesis of oligonucleotides include the use of S-substituted mercaptoethanols, e.g. (36), a new class of phosphoryl protecting groups.82 Oxidation of (36) to the sulphoxide (37) renders the 0

PhSCH CH, 2

2

II

0 Nshlotosuccinimide

II/

+ PhS02CH2CH,0P\

\

0

,

lN-NaOH+ oc

-0-P

11 / \

protecting group very alkali-labile. Another interesting protecting group for sugar hydroxy-groups is the dihydrocinnamoyl residue (38) which can be removed when required by hydrolysis with a-chym~trypsin.~~ Further details have been published8** 86 of 4-(NN-dimethylamino)anilidate (39) as a protect0 PhCH,CH,CO,R (3 8)

ing group for phosphoryl residues. An advantage of (39) is that the purification of intermediates is made easier on account of its basicity. 2-Cyanoethyl-2’,2’,2’-trichloroethylphosphates (40) have been used in the synthesisof oligodeoxynucleotides the phosphoryl groups in the bifunctional (40) can be unmasked either by reduction or by treatment with alkali. Aspects 7’

’*

84 86

C. L. Harvey and R. Wright, Biochemistry, 1972, 11,4012. C. L. Harvey, R. Wright, A. F. Cook, D. T. Maichuk, and A. L, Nussbaum, Biochemistry, 1973, 12, 208. M. S. Poonian, E. F. Nowoswiat, and A. L. Nussbaum, J. Amer. Chem. SOC.,1972,94, 3992. J. Berndt, Angew. Chem. Internat. Edn., 1973, 12, 264. K. L. Agarwal, M. Fridkin, E. Jay, and H. G. Khorana, J. Amer. Chem. SOC., 1973, 95,2020; S . A. Narang, 0. S. Bhanot, J. Goodchild, R. H. Wightman, and S. K. Dheer, ibid., 1972, 94, 6183. A. Taunton-Rigby, J. Org. Chem., 1973, 38, 977. K. Tajima and T. Hata, Bull. Chem. SOC.Japan, 1972, 45, 2608. T. Hata, I. Nakagawa, and N. Takebayashi, Tetrahedron Letters, 1972, 293 1 . J. C. Catlin and F. Cramer, J. Org. Chem., 1973, 38, 245.

154

Organophosphorus Chemistry 0 NC-CH,CH,O$

,P-OR

I1 I

dThd-0-P-CN

C13C-CH20 (40)

SCH ,CH ,CN (41)

of the synthesis of oligoribonucleotides using phosphodi- and phosphotriesters have been d i s c ~ s s e d88, ~and ~ ~ dithymidine OO-phosphorothioate has been prepared from thymidine 5’-S-(2-cyanoethyl) phosphorothioate (41).8s Dinucleoside monophosphates containing 8-bromoadenosinegO or adenine 8-thiocyclonucleoside(20; X = S)91have been prepared from the monophosphates with the aid of DCC. The dinucleoside monophosphate from (20; X = S) and higher oligomersS2have the base residues stacked with a lefthanded screw axis, as do oligomers derived from (20; X = O).93 A number of papers have appeared within the past year on the solid-state synthesis of oligo- and poly-nucleotides. A polymer prepared from styrene and 20% divinylbenzene has been obtained in the form of very small beads with a large surface area.s4This polymer was activated for nucleotide synthesis by benzoylation, treatment with a Grignard reagent derived from 4-bromoanisole, and then chlorination of the resulting 4-methoxytriphenylmethanol groups to give the polymer (42). Displacement of chloride from this modified

polymer occurs during its reaction with the 5’-hydroxy-group of a nucleotide to give the first unit of an oligomer (Scheme 2). Deoxynucleoside phosphorothioates will displace chloride from chlorinated polystyrene to give a monomer bond.s5 After the oligomer attached to the support through a C-S-P has been built up on the insoluble support it can be liberated by the action of aqueous iodine to give an oligodeoxynucleotide with a 5’-phosphoryl

so

J. Smrt, Coil. Czech. Chem. Comm., 1972, 37, 1870. J. Smrt, Tetrahedron Letters, 1972, 3437. A. Malkievicz and J. Smrt, Tetrahedron Letters, 1973, 491. M. Ikehara, S. Uesugi, and M. Kobayashi, Chem. and Pharm. Bull. (Japan), 1972, 20,

O6

2394. S . Uesugi, M. Yasumoto, M. Ikehara, K. N. Fang, and P. 0. P. Ts’o, J, Amer. Chem. SOC.,1972, 94, 5480. M. Ikehara and S. Uesugi, J . Amer. Chem. SOC.,1972, 94, 9189. M. Ikehara, S. Uesugi, and J. Yano, Nature New Biol., 1972, 240, 16. H. Koster and S. Guessenhainer, Angew. Chem. Internat. Edn., 1972, 11, 713; H. Koster and F. Cramer, Annalen, 1972, 766, 6 . H. Sommer and F. Cramer, Angew. Chem. Internat. Edn., 1972, 11, 717.

Phospphates and Phosphonates of Biochemical Interest

155

0

~

C

H

R

C

+ -S-P-OdThd I II I

-0

0 W C H R - s - P - O d TII h d

I

-0

-0 Scheme 2

group. Polylysine has been suggestedssas a polar, insoluble support for the synthesis of oligodeoxynucleotides. The nucleotides are joined to the polylysine side-chains by phosphoramidate bonds, which can be cleaved when required by treatment with isopentyl nitrite. Poly-(3,5-diethylstyrenesulphonyl chloride) has been used in place of tri-isopropylbenzenesulphonyl chloride in nucleotide synthe~is.~? The insoluble poly(styrenesulphony1 chloride) has the advantage that both it and its hydrolysis products are readily removed from a reaction by filtration. A number of polynucleotides containing atypical bases have been prepared recently either by polymerizing ribonucleoside diphosphates with polynucleotide p h o ~ p h o r y l a s e ~or ~ - by ~ ~ ~polymerizing ribo- and deoxyribonucleoside triphosphates with the appropriate polymerase.lo8~ loB An alternative method for the enzymic synthesis of single-stranded polydeoxyribonucleotides involves the use of terminal nucleotidyl transferase.llO The use T. M. Chapman and D. G. Kleid, J.C.S. Chem. Comm., 1973,193. M. Rubenstein and A. Patchornik, Tetrahedron Letters, 1972, 2881. L. L. Gerchman and D. B. Ludlum, Biochim. Biophys. Acta, 1973, 308, 310. 9 B J. Hobbs, H. Sternbach, and F. Eckstein, Biochemistry, 1972, 11, 4336. loo M. A. W. Eaton and D. W. Hutchinson, Biochemistry, 1972, 11, 3162. lol W.Bahr, P. Faerber, and K. H. Scheit, European J , Biochem., 1973, 33, 535. lo8 M. Ikehara, M. Hattori, and T. Fukui, European J . Biochem., 1972, 31, 329. l o 8 M. Ikehara and M. Hattori, Biochim. Biophys. Acta, 1972, 281, 11. lo4 L. Bachner and J. Massoulie, European J. Biochem., 1973, 35, 95. lo5 H. Schetters, H. G. Gassen, and H. Matthaei, Biochim. Biophys. Acta, 1972, 272, 549. lo8 M. Khurshid, A. Khan, and F. M. Rottman, F.E.B.S. Letters, 1972, 28, 25. lo7 J. T. Uchic, M. Uchic, and A. D. Broom, Biochem. Biophys. Res. Comm., 1973,51,494. lo* J. L. Darlix, P. Fromageot, and E. Reich, Biochemistry, 1973, 12,914. l o o W.Rohde and A. G. Lezius, Biochim. Biophys. Acta, 1973, 308, 361. 'lo R. M. Fliigel and F. J. Bollum, Biochim. Biophys. Acta, 1973, 308, 35. ST

156

Organophosphorus Chemistry

for of insoluble polynucleotide phosphorylase,lll or soluble RNase polynucleotide synthesis has also been reported. In an elegant method for the preparation of oligoinosinic IDP and UDP were co-polymerizedwith the aid of polynucleotide phosphorylase (Scheme 3). Hydrolysis of the resulting IDP + UDP polynucleotide

u,

phosphorylase

i, RNase A ii, alkaline phosphatase

(‘P)fl-l‘

i, NaIO, ii, RNH, iii, alkaline phosphatase

(IP)nu

Scheme 3

polymer with RNase A and alkaline phosphatase gave a mixture of oligoinosinic acids bearing a U residue at their 3’-ends. The U-residues were removed by periodate oxidation followed by treatment with a primary m i n e and the oligoinosinic acids were separated by ion-exchange chromatography after their 3’-phosphoryl groups had been removed enzymically. Analytical Techniques and Separation Methods.-Sequence analysis of nucleic acids has continued to receive attention. Although isomeric, free oligodeoxynucleotides cannot be distinguished by mass spectrometry, trifluoroacetylated oligomers are amenable to sequencing by this technique.l14 The phosphodiester bonds in DNA cleave readily in the mass spectrometer and the 3’-terminus of an oligonucleotide can easily be identified. A combination of partial degradation of an oligodeoxynucleotide by snake venom phosphodiesterase followed by the mass spectrometric identification of the fragments has been used to determine its sequence. Other enzymic methods for sequencing polydeoxyribonucleotides involve the successive treatment of the polymer with alkaline phosphatase and a phosphodiesterase,l15 the labelling of the 5’-end of the polymer with polynucleotide kinase followed by DNase digestion and nucleotide ‘rnapping’,lls and the chemical modification of certain C-residues in the polymer with O-methylhydroxylamine followed by partial degradation with an e x o n ~ c l e a s e .In ~ ~ this ~ last instance, exonuclease digestion stops at the modified C-residue and by using exonucleases which digest the oligonucleotide from either the 3’- or the 5’-end, overlapping sequences can be obtained. The stepwise phosphorolysis of oligoribonucleotides by polynucleotide phosphorylase in the presence of 32P-labelledphosphate liberates radioactive J. C. Smith, I. J. Stratford, D. W. Hutchinson, and H. J. Brentnall, F.E.B.S. Letters, 1973, 30, 246. l l a M.J. Rowe and M. A. Smith, Biochim. Biophys. Acta, 1972, 281, 338. 11* S. Tazawa, I. Tazawa, J. L. Alderfer, and P. 0. P. Ts’o, Biochemistry, 1972, 11,3544. 11‘ J. L. Wiebers, Analyf. Biochem., 1973, 51, 542. 116 N. W.Y.Ho and P. T. Gilham, Biochim. Biophys. Acta, 1973. 308, 53. 116 K. Murray, Biochem. J., 1973, 131, 569. 11’ E. D. Sverdlov, G. S. Monastyrskaya, E. I. Budowsky, and M. A. Grachev, F.E.B.S. Letters, 1972, 28, 23 1.

ll1

Phosphates and Phosphonates of Biochemical Interest

157

nucleoside diphosphates from the 3’-end of the oligomer.118 Although this method is promising, its use at present is confined to very short sequences as the successive phosphorolysis steps do not occur quantitatively at each stage. Dihydroxyboryl cellulose11g or polymethacrylate120bind ribonucleotides by the 2’,3’-diol group and have been used to separate mixtures of ribo- and deoxyribo-nucleotides. Lipophilic derivatives of cellulose have been prepared which will retain oligonucleotides which themselves contain lipophilic residues, e.g. 5’-O-trityl groups.121Other analytical techniques which have recently been applied to the separation of nucleic acids are isotachophoresis122 and isoelectric f 0 ~ u s i n g . l ~ ~ 3 Coenzymes and Cofactors Nucleoside Diphosphate Sugars.-The metabolism and function of polyisoprenol sugar phosphates in membrane-associated reactions in vivo have been reviewed.124Early studies on the transfer of glucose from UDPGlc by liver microsomes indicated that dolichol monophosphate (43) was the primary

€

3;,

H CH2C(Me)=CHCH2 CH2CH(Me)CH2CH20PO3H2 (43) acceptor and that the glucose residue was then transferred to an endogenous acceptor. It has now been that this acceptor is an oligosaccharide containing nineteen monomer units which is bound to dolichol by a pyrophosphate link and this glucosylated oligosaccharide is then transferred intact to an endogenous protein. Pyrophosphodiesters of carbohydrates and polyisoprenol alcohols resembling dolichol have recently been synthesized.126 Dolichol phosphate will also accept mannose from GDPMan and transfer it to a pr0tein,1~’and mannophospholipids are formed in cotton fibres.12* The isolation and synthesis of new nucleoside diphosphate sugars has cont i n ~ e d130 , ~and ~ ~ aspects ~ of the biochemistry of poly(ADP-ribose) have been reviewed.131 11s C. Kaufmann, H.Grosfeld, and U. Z . Littauer, F.E.B.S. Letters, 1973, 31, 47. 119 M.Rosenberg, J. L. Weibers, and P. T. Gilham, Biochemistry, 1972, 11, 3629. H Schott, E. Rudloff, P. Schmidt, R. Roychoudhury, and H. Kossel, Biochemistry, 1973, 12, 932. 1111 P. J. Cashion, M. Fridkin, K. L. Agarwal, E. Jay, and H. G. Khorana, Biochemistry, 1973,12, 1985. la* J. L. Beckers and F. M. Everaerts, J . Chromatog., 1972, 71, 380. Ira J. W. Drysdale and P. Righetti, Biochemistry, 1972, 11, 4044. lS4 W. J. Lennarz and M. G. Scher, Biochim. Biophys. Acta, 1972, 265, 417. laL A. J. Parodi, N. H. Behrens, L. F. Leloir, and H. Carminatti, Proc. Nat. Acad. Sci. U.S.A., 1972, 69, 3268. I a 6 C . D. Warren and R. W. Jeanloz, Biochemistry, 1972, 11, 2565. la’ J. B. Richards and F. W. Hemming, Biochem. J., 1972, 130, 77. 1’8 W. T. Forsee and A. D. Elbein, J. Biol. Chem., 1973, 248, 2858. 119 P. K. Kindel and R. R. Watson, Biochem. J., 1973, 133, 227. l a 0 M. Spencer, P. Blackburn, W. Ferdinand, and G. M. Blackburn, Biochem. J., 1973, 131, 421. (a) T. Sugimura, Progr. Nucleic Acid. Res. Mol. Biol., 1973, 13, 127; (6) S. Shall, F.E.B.S. Letters, 1972, 24, 1. 110

158

Organophosphorus Chemistry

Vitamin B6and Related Cornpound~.4’-Ethynylpyridoxine5’-phosphate (44) appears to be a useful reagent for investigating the active site of aspartate as the circular dichroism and ultraviolet spectra of apoaminotran~ferase,~~~ (44)alter on binding to the apoenzyme. The coenzymic activity of several H C

$HO

Ill

C

CH 2~ PO^ H

H O&

AN>

Me

(45)

(44) analogues of pyridoxal 5’-phosphate indicates that the 5’-phosphoryl residue is not essential for activity as the 5’-sulphate (45) shows substantial Insolubilized tryptophanase can be prepared by adding the soluble apo-enzyme to pyridoxal 5’-phosphate which has been attached to Sepharose through an aryl diazo-group (46).13* CHO

kinetics of the reactions between acetyl Coenzyme A

Other Coenzymes.-The

and orth~phosphatel~~ or a r ~ e n a t e suggest l ~ ~ that they are essentially similar and are random bimolecular in type. CoA antagonists, e.g. (47), have been

0

II I

RO-P-0-P, HO

0 ll,*Me OH

(47) R = (Adenos’ine 3’-phosphate)-S’-

HO* HO

OH

I. Y. Yang, P. G . G . Potti, and W. Korytnyk, Fed. Proc., l973,32,589Abs. E. Groman, Y. Z . Huang, T. Watanabe, and E. E. Snell, Proc. Nut. Acad. Sci. U.S.A., 1972, 69, 3297. la‘ S. I. Ikeda and S. Fukui,Biochem. Biophys. Res. Coinm., 1973, 52, 482. S. A. Kyrtopoulos and D. P. N. Satchell, Biochim. Biophys. Acta, 1972, 276, 376. lS0 S. A. Kyrtopoulos and D. P. N. Satchell, Riochim. Biophys. Acta, 1972, 276, 383.

la’

Phosphates and Phosphonates of Biochemical Interest

159

synthesized.13' Analogues of NAD+ which contain formycin (48), 2-aminopurine riboside, or 7-deazapurine riboside in place of adenosine are highly fluorescent in both the oxidized and reduced forms.138Yeast NAD+ pyrophosphorylase will catalyse the synthesis of the 2-amino- and 7-deaza-purine analogues from NMN+ and the respective nucleoside triphosphates. This method was not successful for the synthesis of the formycin analogue, which was finally synthesized chemically from NMN+, formycin 5'-phosphate and DCC; this chemical route was also successfully applied to the preparation of analogues of NAD+ which lack the ribose residue of the adenosine moiety

(49).139All analogues showed catalytic activity with a variety of dehydrogenases, as did a water-soluble, high molecular weight derivative of NAD+ which was prepared by linking the coenzyme to p01yethyleneimine.l~~ From an examination of the crystal structure of thiamine pyrophosphate hydrochloride (50), it has been suggested that the most acidic proton is on the

Me

a-phosphorus atom and that the bridging oxygen atom of the pyrophosphate is not involved in hydrogen-bonding.14132P-labelledphosphoenol pyruvate (51) has been obtained by the trichloroacetonitrile-promoted phosphorylation of b-chlorolactic acid by 32P-labelledorthophosphate in the presence of trieth~1amine.l~~ Presumably, a likely intermediate is (52), which is dehydrochlorinated in situ. M. Shimizu, 0. Nagase, Y. Abiko, T. Hosokawa, and T. Suzuki, Jap. P. 72 05 552 (Chem. Abs., 1972, 76,, 127 382.) la* D. C. Ward, T. Horn, and E. Reich, J. Biol. Chem., 1972, 247, 4014. R. Jeck and G. Wilhelm, Annalen, 1973, 531. 140 J. R. Wykes, P. Dunnill, and M. D. Lilly, Biochim. Biophys. Acta, 1972,286,260. l P 1 J. Pletcher and M. Sax, J. Amer. Chem. Soc., 1972,94,3998. 14' H. F. Lauppe, G. Rau, and W. Hengstenburg, F.E.B.S. Letters, 1972,25, 357. l*'

Organophosphorus Chemistry

160 CICH,CH(OH)CO,H

+

H,32P04

CC'BCN>

4 Naturally Occurring Phosphonates Two new syntheses of 2-aminoethylphosphonicacid (53)have been reported.145 Treatment of the hydrazidate of diethyl phosphonopropionic acid with nitrous acid will yield (53), as does the catalytic reduction of diethyl cyanomethylphosphonate in the presence of ammonia. Although the biosynthesis of (53) has been studied in detail in Tetrahymena p y r i f ~ r m i sno ,~~ studies ~ have been carried out until recently with animals. However, it has now been reported that (53) is not synthesized in rat liver as no incorporation of radioactivity

H O J PCH(OH)C,H H~ ' 0 (54)

(55)

into (53) from known precursors could be On the other hand, large amounts of (53) and the related (2-amino-l-hydroxyethy1)phosphonic acid (54) occur in the plasma membranes of a1110ebae.l~~ The synthesis has been reported of a homologue of an a-monoetherphosphonocephalinwhich occurs in 7'. pyrifo~mis.~'~ The antibiotic phosphonomycin (or, as it now appears to be called,148 14* 144

14'

140

14' 149

A. F. Isbell, J. P. Berry, and L. W. Tansey, J. Org. Chem., 1972, 37, 4399. M. Horiguchi, J. S. Kittredge, and E. Roberts, Biochim. Biophys. Acta, 1968,165, 164. J. A. Alhadeff, J. T. Van Bruggen, and G. D. Daves, jun., Biochim. Biophys. Acta, 1972,286, 103. E. D. Korn, D. G. Dearborn, H. M. Fales, and E. A. Sokoloski, J . Biol. Chem., 1973, 248, 2257. E. Baer and H. Basu, Canad. J . Biochem., 1972,50,988. P. J. Cassidy and F. M. Kahan, Biochemisfry, 1973, 12, 1364.

Phosphates and Phosphonates of Biochemical Interest

161

fosfomycin) (55) inhibits the formation of bacterial cell walls by preventing the transfer of an en01 pyruvate residue from phosphoenol pyruvate (51) to UDP-GlcNAc. Proteolytic digestion of the complex formed between ( 5 5 ) and the transferase enzyme yields (56), and hence (55) is probably bound to the transferase through a cysteinyl residue. Unlike the free enzyme, the transferase(55) complex is no longer inhibited by N-ethylmaleimide, which also indicates that a cysteinyl side-chain is involved in the formation of the complex. It is that covalent addition-elimination of a sulphydryl group across the C=C bond of (51) occurs during the enzymic reaction. Since (55) interferes with the reaction, both (51) and ( 5 5 ) must fit into the active site of the enzyme and it may be that the relatively flexible (51) is distorted during the reaction to assume a shape similar to that of (55). NH2

I

HOzCCHCH2CH2

I

0 II

(PhCH20)2PCHNZ

0

Me

'O\

!(*cli12Ph)2

(58)

New intermediates in the synthesis of ( 5 5 ) include (57)149 and (58).150 The latter reacts with acetaldehyde to give racemic (55). 5 Oxidative Phosphorylation Mitochondria1 electron transport and energy conservation have been reviewed151and the phosphorylation potential of respiring mitochondria has been determined.152In view of the large adverse phosphorylation potential which appears to arise in respiring mitochondria, it has been calculated that a redox potential difference of at least 350 mV between substrate (succinate) and oxygen is necessary for ATP synthesis to take place. An ATP-inorganic phosphate exchange similar to that catalysed by mitochondria can be simulated by a reaction system containing oxidized glyceraldehyde 3-phosphate dehydr0gena~e.l~~ The latter contains a E. J. Glamowski, C. B. Rosas, M. Sletzinger, and J. W. Wantuck, Fr. P. 2 074 329 (Chem. Abs., 1972,77,62 132). l*O R. A. Firestone, U.S.P. 3 668 197 (Chem. Abs., 1972, 77, 114 560). lr1 D. F. Wilson, P. L. Dutton, M. Erecinska, J. G. Lindsay, and N. Sato, Accounts Chem. Res., 1972, 5, 234. 16* E. C. Slater, J. Rosing, and A. Mol, Biochim. Biophys. Acta, 1973,292,534. lba W. S.Allison and L. V. Benitez, Proc. Nut. Acad. Sci. U.S.A., 1972, 69, 3004.

l4#

162

Orgunophosphorus Chemistry

sulfenic acid residue, and a model for mitochondria1 oxidative phosphorylation has been put forward (Scheme 4) which includes a sulfenyl-carboxylate

H2PO;

m

-rl-l--

OP03HADP . 7 ‘--r-rTHS SH C HS SH COZ-

0” ‘oPO3H-

+ B + H20

3. ATP

Scheme 4

anhydride as a non-phosphorylated ‘high energy’ intermediate and an acyl phosphate as a phosphorylated ‘high energy’ intermediate. (59 ; Oxidation of 1,4,5,6-tetrahydro-6-hydroxy-l-n-propylnicotinamide R = C,H,) by NNN’N’-tetramethyl-p-phenylenediamineand oxygen in aqueous pyridine in the presence of orthophosphate is accompanied by phosphoryl A possible reaction sequence is outlined in Scheme 5 and it is suggested that an intermediate similar to (60) may be formed in vivo from NADH.

E.J. H. Bechara and G . Cilento, Biochemistry, 1972,11, 2606.

Phosphates and Phosphonates of Biochemical Interest

163

6 Sugar Phosphates The synthesis and properties of carbohydrates which contain modified phosphate groupsfSShas been recently reviewed, as have methods for the determination of sugar The chemical synthesis of a number of sugar phosphates have been r e p ~ r t e d , and ~ ~ ~acetal - ~ ~ phosphonates ~ (61) have been prepared from 0-acetylglycosyl halides.lsl

I

c=o I

+ H,N -Lys-Aldolase

I

$

C=N-Lys-AAldoIase

I

CH2OH

CHzOH

4-H+

CH~OPO~H~

I I

C=N-Lys CHOH

1

-Aldolase

CH 20P03Hz

I

c=o I

HO-C-H

I I c=o

H-C-OH

E. E. Nifant’ev and I. P. Gudkova, Russ. Chem. Rev., 1972, 41, 850. H. G. Pontis and L. F. Leloir, Analyt. Chem. Phosphorus Compounds, 1972, 617. lK7 J. Stverteczky, P. Szab6, and L. Szab6, J . C . S. Perkin I, 1973, 872. lS8 J. S. Prihar and E. J. Behrman, Biochemistry, 1973, 12, 997. lse G. J. F. Chittenden, Carbohydrate Res., 1972, 25, 35. 160 E. M. Bessell and P. Thomas, Biochem. J. Mol. Aspects, 1973, 131, 77. 161 H. Paulsen and J. Thiem, Chem. Ber., 1973, 106, 115, 132. lS6

164

OrganophosphorusChemistry

The reaction of fructose 1,6-diphosphate with aldolase to give dihydroxyacetone phosphate (62) and glyceraldehyde 3-phosphate has been shown to proceed through the formation of a carbanion derived from aldolase and (62).lS2The aldolase-(62) complex reacts with tetranitromethane to give hydroxypyruvaldehyde phosphate (63), formed by oxidation of the complex, and D-5-ketofructose 1,6-diphosphate(64), which is presumably formed in an aldolase-catalysed condensation of the complex with (63). A phosphoryl enzyme intermediate is formed during the hydrolysis of glucose 6-phosphate by glucose 6-phosphatase,la3and pronase digestion of the intermediate liberates N-3-phosphorohistidine. It is unlikely that the phosphorohistidine transfers its residue to serine, as is commonly found in hydrolytic enzymes, as no phosphorylated serine could be detected in the enzymic digest. The structures have been determined of a cell wall phoso ~ of ~~ a phosphomannan ~~~~ phoropolysaccharideof a strain of S t a p h y Z o ~ and excreted by the yeast Hansenula holstis.lsS

7 Phospholipids The biosynthesis of lipids in bacterial membranes16s and phospholipid metabolismla7have been the subjects of recent reviews. lH N.m.r. studies168 reveal that glycerophosphatidyl choline, unlike glycerophosphatidyl ethanolamine, has the same conformation in solution as in the solid sfate.lS9Addition of praseodymium ions to lecithin vesicles enables phospholipids inside and outside the vesicle membrane to be differentiated,170as the 31Pn.m.r. chemical shifts of the two types of phospholipid are altered to different extents. 12Stearic acid nitroxide has been enzymically incorporated into the membrane phospholipids of rat liver microsomes. The spin-labelled lecithin produced was then isolated and used to examine the ordering of phospholipid layers in the membrane.171 In a simple synthesis of analogues of lecithin derived from ethylene glycol, the cis-glycol group in sn-glycero-3-phosphorylcholineis cleaved with periodate and the resulting phosphorylglycollaldehyde reduced with borohydride.17* A number of other phospholipids has been isolated and characterized during

H. J. Healy and P. Christen, J. Amer. Chem. SOC.,1972, 94, 7911. F. Feldman and L. G. Butler, Biochim. Biophys. Acta, 1972, 268, 698. l e d A. R. Archibald and G. H. Stafford, Biochem. J., 1972, 130, 681. lo6 R. K. Bretthauer, G. J. Kaczorowski, and M. J. Weise, Biochemistry, 1973, 12, 1251. l e e W. J. Lennarz, Accounts Chem. Res., 1972, 5, 361. Ie7 W. C. McMurray and W. L. Magee, Ann. Rev. Biochem., 1972, 41, 29. lea J. Dufourcq and C. Lussan, F.E.B.S. Letters, 1972, 26, 35. l a g M. Sundaralingam, Nature, 1968, 217, 35. V. F. Bystrov, Y.E. Shapiro, A. V. Viktorov, L. I. Barsukov, and L. D. Bergelson, F.E.B.S. Letters, 1972, 25, 337. A. Colbeau, P. M. Vignais, and L. H. Piette, Biochem. Biophys. Res. Comm., 1972, 48, lea

1495.

K. K. Yabusaki and M. A. Wells, Biochim. Biophys. Acta, 1973, 296, 546.

Phosphates and Phosphonates of Biochemical Interest

165

the past year,173-175and the identification of a ceremide aminophosphonate by g.1.c.-mass spectrometry has been achieved.178 8 Enzymology Enzymic phosphoryl group and the interconversion of active and inactive forms of enzymes178have been the subjects of recent reviews. Phosphoryl enzymes have been identified as intermediates in several enzymic reactions. For example, phosphoglycerate mutase, which catalyses the interconversion of 2- and 3-phosphoroglyceraldehyde,has been shown to give a phosphorylated intermediate both for the and human erythrocytelso enzymes. The phosphoryl enzyme in the latter instance is very sensitive to acid and may be a phosphorohistidine. Phosphoglucomutase is another enzyme which is phosphorylated while catalysing an isomerization reaction ;181 furthermore, this enzyme is inactivated by 1,2-anhydrohexitoI 6-phosphates (65).lS2A pyrophosphoryl enzyme, the first to be detected, is formed in pyruvate phosphate dikinase from Propionibacteria.lE3

I

CH20P03H2 (65)

17* 176

170

l7I

170 ‘*O

M. Matsumoto and M. Miwa, Biochim. Biophys. Acta, 1973, 296, 350. N. Shaw, P. F. Smith, and H. M. Verheij, Biochem. J., 1972, 129, 167. P. Kemp, R. M. C. Dawson, and R. A. Klein, Biochem. J , 1972,130,221. T. Matsubara and A. Hayashi, Biochirn. Biophys. Acta, 1973, 296, 171. J. F. Morrison and E. Heyde, Ann. Rev. Biochem., 1972, 41, 29. H. L. Segal, Science, 1973, 180, 25. H. G. Britton, J. Carreras, and S. Grisolia, Biochemistry, 1972, 11, 3008. Z. B. Rose and R. G. Whalen, J. Biol. Chem., 1973, 248, 1513. K. J. Schray, S. J. Benkovic, P. A. Benkovic, and I. A. Rose, J. Biol. Chem., 1973, 248, 2219. E. L. O’Connell and I. A. Rose, J. Biol. Chem., 1973, 248, 2225. Y. Milner and H. G. Wood, Proc. Nat. Acad. Sci. U.S.A., 1972, 69, 2463.

I66

Organophosphorus Chemistry

Yeast inorganic pyrophosphatase has been extensively studied recently. New methods of purification have been developed,184and with the availability of large amounts of crystalline enzyme the existence of two identical subunits has been demonstrated and a partial sequence of their N-terminal ends has been elucidated.186Proton relaxation rates measured by n.m.r. show that manganese can bind directly to the enzyme at two sites186and kinetic together with active-site mapping, have led to a possible mechanism of action for this enzyme.lS8In the active site (66), a pyrophosphate ion is bound to the enzyme by a magnesium ion and an arginine residue. The change in proton relaxation rates of water when manganese binds to pyruvate kinase in the presence of phosphoenol pyruvate (51) or its analogues has been used as a method for studying the active site of the lgo Phosphoryl co-ordination from (51) to an enzyme-bound manganese ion in the active site which was suggested by this n.m.r. technique is confirmed by 31P n.m.r. measurements. It is also suggested that co-ordination of the carboxy-group of (51) to an enzyme-bound potassium ion changes the conformation of the enzyme-Mn2+-(5 1) complex to its catalytically active form. Triose phosphate isomerase is another enzyme which has been studied extensively in the past year, and the isolation,1s1 pH dependence,lg2and active-site labellinglS3of this enzyme have been reported. The involvement of a glutamic acid residue in the active site has been demonstrated by the covalent labelling of the enzyme by bromohydroxy [14C]acetonephosphate.lS3 The importance of a glutamic residue is confirmed by its esterification by Dor L-glycidol phosphates (67)lg4and by the isolation of the active-site peptide containing a glutamate residue.lg5 Thymidylate synthetase catalyses the reductive methylation of dUMP to dTMP with the concomitant conversion of 5,1O-methylenetetrahydrofolic acid (68) into 7,8-dihydrofolic acid. The synthetase in the presence of (68) is rapidly inactivated by 5-fluoro-2’-deoxyuridylic acid,lg6and this is accompanied by the loss of the 5-fluorouridine chromophore in the ultraviolet ln4

B. S. Cooperman, N . Y . Chiu, R. H. Bruckmann, G. J. Bunick, and G . P. McKenna,

Biochemistry, 1973, 12, 1665. R. L. Heinrickson, R. Sterner, C. Noyes, B. S. Cooperman, and R. H. Bruckmann, J. Biol. Chem., 1973, 248, 2521. 1 8 0 B. S. Cooperman and N. Y . Chiu, Biochemistry, 1973, 12, 1670. lS7 J. W. Sperow, 0. A. Moe, J. W. Ridlington, and L. G . Butler, J. Biol. Chem., 1973,248, 2062. B. S. Cooperman and N. Y . Chiu, Biochemistry, 1973, 12, 1676. la9 T.Nowak and A. S. Mildvan, Biochemistry, 1972,11,2813. lSo T. Nowak and A. S. Mildvan, Biochemistry, 1972, 11, 2819. l B 1 S . J. Putman, A. F. W. Coulson, I. R. T. Farley, B. Riddleston, and J. R. Knowles, Biochem. J., 1972, 129, 301. l B f iB. Plaut and J. R. Knowles, Biochem. J., 1972, 129, 311. l B 8S. De la Mare, A. F. W. Coulson, J. R. Knowles, J. D. Priddle, and R. E. Offord, Biochem. J., 1972,129, 321. lo* K. J. Schray, E. L. O’Connell, and I. A. Rose, J. Biol. Chem., 1973, 248, 2214. I s 6 F. C. Hartman and R. W. Gracy, Biochem. Biophys. Res. Comm., 1973,52, 388. D. V. Santi and C. S. McHenry, Proc. Nut. Acad Sci. U.S.A., 1972, 69, 1855. la6

Phosphates and Phosphoitates of Biochemical Interest

167

spectrum. It is suggested that a covalent intermediate is formed between the synthetase and the 6-position of 5-fluorouracil ring (69).

R

(69)

Acetyl cholinesterase is inhibited by diethyl phosphor~chloridate~~~ and the chloridate of 1,3,2-dioxaphosphorinan 2-oxide (70).lg8 In marked contrast to inhibition by diethyl phosphoryl derivatives, inhibition of (70) is spontaneously and rapidly rever~ib1e.l~~ This difference in reactivity between the two phosphoryl enzymes may be due to steric strain in (70) caused by the binding of a comparatively large residue to the active site of the cholinesterase. 9 Other Compounds of Biochemical Interest The incorporation of geranylgeranyl pyrophosphate (71) into lycopene and other carotenoids appears to follow the same pathway as that taken during the incorporation of farnesyl pyrophosphate into ~ q u a l e n e .Head-to-head ~~~ condensation of two molecules of (71) leads to a cyclopropyl derivative, prelycopersene pyrophosphate (72),200which is enzymically converted, in the presence of NADPH, into lycopersene (73), a carotenoid precursor.2o1 Farnesyl pyrophosphate synthetase from pig liver is capable of synthesizing homologues of farnesyl pyrophosphate, e.g. (74), from 3-ethylbut-3-enyl pyrophosphate,202or homofarnesyl pyrophosphate (75) from 3-methylpent-2enyl p y r o p h ~ s p h a t e .A~ ~similar ~ enzyme has been isolated from pumpkin fruit.20* Organic polyphosphates markedly decrease the affinity of haemoglobin for oxygen and, for example, 2,3-diphosphoroglycerate (76) can act as a regulator for oxygen in tissues.206The binding of (76) to human haemoglobin has recently been studied by 31Pn.m.r.206and it has been shown that an a-chain binds to (76) before a p-chain. Pyridoxal phosphate has a similar effect to (76) on haemoglobin but other pyridoxine derivatives are inactive, suggesting that lo'

lo8 loo

aoo

Y.Ashani, P. Wins, and I. B. Wilson, Biochim. Biophys. Acta, 1972,284, 427. Y.Ashani, S. L. Snyder, and I. B. Wilson, Biochemistry, 1972, 11, 3518. E. Beytia, A. A. Qureshi, and J. W. Porter, J. Biol. Chem., 1973, 248, 1856. A. A. Qureshi, F. J. Barnes, E. J. Semmler, and J. W. Porter, J. Biol. Chem., 1973,248, 2755.

*01

F. J. Barnes, A. A. Qureshi, E. J. Semmler, and J. W. Porter, J. Biol. Chem., 1973,248, 2768.

*OS *Oa

lo'

K. Ogura, T. Koyama, and S. Seto, J.C.S. Chem. Comm., 1972, 881. A. Polito, G. Popjak, and T. Parker, J. Biol. Chem., 1972, 247, 3464. T. Nishino, K. Ogura, and S. Seto, J. Amer. Chem. Soc., 1972, 94, 6849. R. Benesch, R. E. Benesch, and C. I. Yu, Proc. Nat. A c ~Sci., . U.S.A., 1967, 59, 526. W. H. Huestis and M. A. Raftery, Biochem. Biophys. Res. Comm., 1972,49,428.

168

Organophosphorus Chemistry

Phosphates and Phosphonates of Biochemical Interest

169

CH,OPO,H,

I

CHOP03H2

I

COtH (76)

both the phosphoryl and the aldehyde groups are essential for binding.*07 Reduction of the haemoglobin-pyridoxal phosphate complex with borohydride gave a haemoglobin in which the pyridoxine residue was attached to the N-terminal valine of a p-chain. Reaction of pyridoxal phosphate with oxyhaemoglobin led to modification of an a-chain. Deuteriohaemin IX dimethyl ester derivatives in which a phosphodiester is the fifth ligand for iron have been prepared and are slowly hydrolysed in neutral aqueous solution to haematin-like OH I

OH

I

HN=CNHCH,OPOCH,CHCO,H

I

NH2

II

0

(1.3

I

HN=CNHCH,OPOCH,CHCO,H

I

NMe,

NH

I

II

NMez

0

H203P' (78)

.O

The stereochemistry of the ionic binding of phosphate to arginine residues in enzymes has been deduced from X-ray crystallographic studies with model guanidinium C O ~ ~ O U An ~ ~arginine-containing S . ~ ~ ~ phosphagen (77) and its N-phosphoro-derivative (78) related to lombricine have been isolated from an echiuroid worm.21o Biocidal organophosphorus compounds have been reviewedalland an antitumour agent, cyclophosphamide (79),has been shown to be metabolized in rabbits to the oxygenated form (80) and its hydrolysis product (81).212 R. E. Benesch, R. Benesch, R. D. Renthal, and N. Maeda, Biochemistry, 1972, 11, 3576. C. S. Russell, J. Landis, and N. Bocian, Arch. Biochem. Biophys., 1972, 153, 398.

F. A. Cotton, E. E. Hazen, jun., V. W. Day, S. Larsen, J. G. Norman, jun., S. T. K. Wong, and K. H. Johnson, J. Amer. Chem. SOC.,1973,95,2367. *la N. van Thoai, Y. Robin, and Y. Guillou, Biochemistry, 1972, 11, 3890. N. N. Mel'nikov, 2.Chem., 1972, 12, 201. ¶ l a A. Takamizawa, Y. Tochino, Y.Hamashima, and T. Iwata, Chem. and Pharrn. Bull. (Japan), 1972, 20, 1612.

*OD

Ylides and Related Compounds BY S. TRIPPETT

1 Methylenephosphoranes Preparation.-Electrolytic reduction at a mercury cathode in acetonitrile,

+

DMF, or HMPT of the cations Ph3PCHR1R2(R1=H, R2=PhC0 or Ph; R1 and R2= Ph) gave ylide, phosphine, and hydrocarbon:'

+

+

2e-

+

-

Ph,PCHR1R2 .-•Ph3P CHR1R2

+

-

Ph3PCHR1R2 CHR1R2+Ph3P=CR'R2 + CH2R1R2 Further examples of the use of epoxides as the source of base in olefin synthesis have appeared.2Particularly noteworthy is the synthesis of the furylolefin (1); previous attempts to prepare this from furfuraldehyde and preformed ylide had failed. Polymeric ylides have been used in stereospecific Ph,;(CH,),Me

Br-

+ O/ C\ H

O

0

PhMeC=CHPr 100%; 97.5% cis

*CHt-CH

+ PhCOMe (2)

Ph MeC=CH Pr 5 9 % ; cis: trans, 14 : 86

olefin ~yntheses.~ Thus the polymer (2) with acetophenonegave almost entirely cis-olefin under salt-free conditions and largely trans-olefin via the p-oxidoylide. Besides the expected olefins, cis- and trans-l-styrylazulenes and l-methyl-

a

J. M. SavCant and S. K. Binh, Bull. SOC.chim. France, 1972, 3549. J. Buddrus, Angew. Chem. Internat. Edn., 1972, 11, 1041. W. Heitz and R. Michels, Annalen, 1973, 227.

170

Ylides and Related Compounds

171

azulene were also obtained4 when the ylide (3) was generated using phenyllithium in DMF or dimethylacetamide and used in olefin synthesis. The benzaldehyde which leads to the styrylazulenes probably comes from the

PhLi

+ HCONMe2 --+PhCH(G)NMe,Li+

._f

PhCHO

+

Me,NLi

(4)

1Azc.*h3 AzMe

t

A z ~ H ,t AzCH,-PPh,-&-CHPh-NMe, ?

-6'.

A z = l-Azulenyl Scheme 1

adduct (4) of phenyl-lithium and a i d e while the l-methylazulene, which was not formed by hydrolysis of unchanged salt, could arise from attack of the adduct (4) on phosphonium salt, as shown in Scheme 1. In alcoholic solution, triphenylphosphine and dimethyl acetylenedicarboxylate gave6 the p-alkoxyphosphoranes (5). The effects of varying the Ph3P

+

MeO,CCECCO,Me -+

Ph,k(CO,Me)=CCO,Me . 0 . 1

Ph ,P=C(CO ,Me)C H(0R)CO ,Me +--

-t-

Ph,PC(CO,Me)=CHCO ,Me RO-

(5)

R1,P

+

R26=NRPh -+ R1,P=CR2-N=NPh (6)

* J. 0. Currie, jun., R. A. LaBar, R. D. Breazeale, and A. G. Anderson, jun., Annalen, 1973, 166.

I. F. Wilson and J. C. Tebby, J.C.S. Perkin I , 1973, 2830.

172

Organophosphorus Chemistry

substituents on the preparation of the azo-phosphoranes (6) from phosphines and nitrile-imines have been studied.g Attempts to generate the methylenephosphorane from trimesitylmethylphosphonium bromide gave7 the benzylphosphine (7), the product of the first recorded Stevens rearrangement of a phosphorus ylide. Similar rearrangements of other ylides are in general catalysed by nickel complexes. Reactions.-The synthesis of cyclic compounds using phosphorus ylides has been reviewed.* Halides. The gold complex (8) with increasing quantities of methylenetrimethylphosphorane gaveQsuccessively the salt (9), the salt (lo), and finally with an excess of reagent the complex (11). Similar products were obtained from the silyl-phosphorane Me,P=CHSiMe,, but the bis-silyl-phosphorane Me,P=C(SiMe,), gave only the analogue of (9). Copper(1) chloride and the silver complex [Me,PAgCl], with methylenetrimethylphosphorane gavelo the copper@ and silver analogues of (1 1) quantitatively. Me,PAuCI

+ Me,P=CH,

(8) +/ Me,P,

CH&CH:,

cH, LC

\+

PMe,

H’2

Ph,P=CHCOAr (12)

+

+

i

-

Me,PAuCH,PMe, CI(9)

1

Me,P=CH,

Me,kH,&CH26Me, CI-

Me,SiCI

(10)

+

Ph,PCH-CAr C1-

I

Me:,Si+O (1 3)

II

The phosphonium salts obtainedll from the stable phosphoranes (12) and trimethylchlorosilane show carbonyl absorption in the i.r. at 1480 cm-l and are formulated as (13). Heating gave back the starting materials and attempts to generate the corresponding ylides failed. Details have appeared12of the reactions of methylene- and silylmethylenephosphoranes with chloro- and dichloro-disilanes. S. P. Konotopova, V. N. Chistokletov, and A. A. Petrov, J . Gen. Chem. (U.S.S.R.), 1972,42,2406. F. Heydenreich, A. Mollbach, G. Wilke, H. Dreeskamp, E. G. Hoffmann, G. Schroth, K. Seevogel, and W. Stempfle, Israel J. Chem., 1972, 10, 293. H. J. Bestmann and R. Zimmermann, Chem.-Ztg., 1972, 96, 649. H. Schmidbauer and R. Franke, Angew. Chem. Internat. Edn., 1973,12,416. l o H. Schmidbauer, J. Adlkofer, and W. Buchner, Angew. Chem. Internat. Edn., 1973, 12, 415. l1 S. Kato, T. Kato, M. Mizuta, K. Itoh, and Y. Ishi, J. Organometallic Chem., 1973, 51, 167. H. Schmidbauer and W. Vornberger, Chem. Ber., 1972, 105, 3173. a

Ylides and Related Compounds 2 Ph,P=CHR

+

173

CGFC

Ph,P=CRC,jFS

+

-b

PhaPCHZR F-

(1 5 )

(14)

Hexafluorobenzene with the reactive phosphoranes (14; R = H or Ph) gavel3the ylides (15), isolated as a stable compound when R= Ph and trapped with p-nitrobenzaldehyde when R = H. A general alkylation of heterocyclic involves the reaction of nuclear-chlorinated heterocyclics with reactive phosphoranes to give ylides which are then hydrolysed. The ylides can also be used in olefin synthesis. In this way 4-chloro-2-methylquinoline CH=PPh

@Me

+ 2Ph3P=CH,

3

_j

CH=CHPh W

M

e

(17)

with methylenetriphenylphosphoranegave the ylide (16), hydrolysis of which gave 2,4-dimethylquinoline (79 %) and which with benzaldehyde gave the olefin (17; 69%). Similar reactions have been used16 in syntheses of quinine and related alkaloids. Full accounts have appearedla of the n.m.r. and alkylation of fomylstabilized phosphoranes. Cyclopropylacetic acid was obtained" as shown in Scheme 2. 2 D C H Z 6 P h , Br-

. .. *

[)C(CO,Me)=PPh,

+DCH,h,

CI-

Reagents: i, PhLi-ether; ii, CIC0,Me; iii, NaOH-H,O.

Scheme 2

*' l1

N. A. Nesmeyanov, S. T. Berman, and 0. A. Reutov, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 605. E. C. Taylor and S. F. Martin, J. Amer. Chem. SOC.,1972, 94, 2874. E. C. Taylor and S. F. Martin, J. Amer. Chem. SOC.,1972, 94, 6218. C. J. Devlin and B. J. Walker, Tetrahedron, 1972, 28, 3501. A. Maercker and W. Theysohn, Annalen, 1972, 759, 132.

174

Organophosphorus Chemistry

Carbonyls. Studies on the kinetics of the reactions of p-nitrobenzaldehyde with phenacylidenetriphenylphosphoranelsand with a number of fluorenylideneph~sphoranes~~ led to the conclusion that the initial, ratedetermining, step involves a four-centred transition state of low polarity leading directly to a 1,2-oxaphosphetanand not to a betaine. However, the similar rates of reaction of benzaldehyde with the cyclic (18; R = P h or

QTO

Ph,P=CHR

Ph/ \CHR

(19)

(18)

C0,Et) and corresponding ‘acyclic’ ylides (19; R = Ph or C0,Et) led2*to the opposite conclusion: direct formation of 1,Zoxaphosphetans would be expected to lead to increased rates of reaction for the cyclic ylides (18) because of relief of angle strain at phosphorus. A high yield of stilbene was obtained21from benzaldehyde and benzyltri(2-fury1)phosphonium bromide in methanolic methoxide solution. Because of the high leaving-group ability of the 2-fury1 group, this implies that the

-I-

Fu,P-CHPh

I

LCHPh

MeO-

+ PhCHO

-I-

Fu,PCHIPhBr-

-

-

M&H

Fu,PO

+ PhCH=CHPh

+ FuaP-CHPh

I

HO-CHPh

*

Fu,$-CPh

II

CHPh (20)

vinylphosphonium salt (20) is not an intermediate. In contrast to the rearrangements observed in the reactions of methyltriphenylphosphonium salts with benzaldehyde in ethanolic ethoxide solution, the furylphosphonium salts (21 ; n= 1, 2, or 3) under the same conditions gave normal olefin syntheses.

Y

Ph2P(:O)CHPh*CH ,Ph

EtOH-NaOEt

Fu,Ph,-,,kH,

+ PhCHO

(21)

FunPh,-nPO

ao s1

+ PhCH=CHZ

G. Aksnes and F. Y. Khalil, Phosphorus, 1972, 2, 105. P. Frayen, A d a . Chem. Scand., 1972, 26,2163. I. F. Wilson and J. C. Tebby, J.C.S. Perkin I, 1972, 2713. D. W. Allen, B. G. Hutley, and T. C. Rich, J.C.S. Perkin I l , 1973, 820.

Ylides and Related Compounds

175

The use of sodium a-hydroxysulphonates (bisulphite addition compounds) in olefin syntheses instead of aldehydes leads to higher yields of purer products.22The t-butyldimethylsilyl group has been to protect hydroxygroups during reactions involving the use of ylides. It is rapidly removed at 25 "C in THF containing tetrabutylammonium fluoride. A striking demonstration that Wittig olefin syntheses using reactive ylides proceed under much milder conditions than normally employed was provided2* in the synthesis of the unstable cis-divinylcyclopropane(23). Addition of the aldehyde (22) to methylenetriphenylphosphorane in DMSO-isopentane at 5 "C,reaction, and quenching in brine at - 20 "Ctook about 1 min.

+

Ph,P=CH2

_.f

(23)

D

D

Ill

Ill

11

i' /

(26)

Besides the expected deuterioallene (25), the isomer (26) was also obtained when the ketone (24) labelled with deuterium at the free acetylenic position was treated with methylenetriphenylph~sphorane.~~ Scrambling of deuterium between the free acetylenic position and the methylenephosphoraae is presumably faster than addition of the phosphorane to the carbonyl. The la

l4 *&

G. Koszmehl and B. Bohn, Angew. Chem. Internat. Edn., 1973, 12, 237. E. J. Corey and A. Venkateswarlu, J. Amer. Chem. SOC.,1972, 94, 6190. J. M. Brown, B. T. Golding, and J. J. Stofko, jun., J.C.S. Chem. Comm., 1973, 319. P. Gilgen, J. Zsindely, and H. Schmid, Hell?.Chim. Acta, 1973,56,681.

176

4 /

0rganophosphor us Chemistry

0:"l \

same phosphorane did not react with the ketones (27) and (28). Among other unsuccessful olefin syntheses reported is that between the tetralone (29) and the ylides Ph3P=CH(CHz),COzR.26

d

+ Ph,P=CHCOMe

Me0

\

-+

(31)

(3 0)

+ 0

(32)

The olefins (32) and (35) were unexpected products from the reactions of the acetonylidenephosphorane (31) with the ketone (30) and the lactone

L (33)

(341,

O (35)

(33), respecti~ely.~~ They may be formed via attack of carbanions, e.g. (36), on ketophosphonium salt followed by elimination of phosphine oxide. CH 2-PPh

3

CH Z-PPha

c-oMe

Me

-

(36) I0

D. Taub, R. D. Hoffsommer, C. H. KUO,H. L. Slater, Z. S. Zelawski, and N. L. Wendler, Tetrahedron, 1973, 29, 1447. H. T. J. Chan, J. A. Elix, and B. A. Ferguson, Svnrheric Comm., 1972, 2, 409.

(32)

Ylides and Related Compounds

177

A new synthesis of terminal acetylenesz8is based on the reaction of aldehydes with dibromomethylenetriphenylphosphorane,formed in situ from carbon tetrabromide and triphenylphosphine, and treatment of the resulting dibromo-olefins with butyl-lithium or lithium amalgam (Scheme 3). 2 Ph3P

+ CBr,

RCHO

+

__f

Ph,P=CBr,

Ph,PBr, 4- Ph,P=CBr,

-+ RCH=CBr,

3RCzCLi 80-95 %

80-!90% 1Li-H.

RC-CH Scheme 3

The reaction between salicylaldehyde and the crotylphosphonium salt (37) in the presence of sodium hydride has now been to give a mixture of all four geometrical isomers of the diene (38). The same mixture was obtained

1 : 1.4

(40)

67%

starting from pure trans-crotyl salt. Among other olefin syntheses worthy of note were the use of muconic dialdehyde in the synthesis of aw-di-l-naphthyland cxw-di-2-naphthyl-polyene~~~ and the preparation31of the aldehydes (39) and (40) from benzylidenetriphenylphosphorane and a five-fold excess of 0-phthalaldehy de. The p-oxidoylide synthesis of allylic alcohols, using formaldehyde as the second carbonyl component, gave32the expected olefins (41) when the first ph3p=CHR1

PdxidoYlide_ synthesis '

R2R3C=CR1CHZOH

+

R2R3C(OH)CR1=CHz

(41)

(42)

Reagents: R2R3C0, -78 "C;BuLi, - 78 OC; H,CO, -78 "C;R.T. lo

ao

E. J. Corey and P. L. Fuchs, Tetrahedron Letters, 1972, 3769. R. Hug, H.-J. Hansen, and H. Schmid, Helu. Chim. Acta, 1972, 55, 1828. A. Yasuhara, S. Akiyama, and M. Nakagawa, Bull. Chem. SOC.Japan, 1972,45, 3638. A. A. Baum, J. Amer. Chem. SOC., 1972, 94,6866. M. Schlosser and D. Coffinet, Synthesis, 1972, 574.

178

Organophosphorus Chemistry

component was a long-chain aldehyde but also the olefins (42), formed by elimination of the oxygen derived from the formaldehyde, when the first component was a hindered aldehyde or a ketone. In extreme cases, e.g. with acetone as the first carbonyl reagent, only the olefins (42)were obtained. The use in analogous /?-oxidoylide syntheses of a nitrile instead of the second carbonyl compound gave the +unsaturated ketones (43).33

Reagents: i, R2RR3CO; BuLi; R4CN; ii, H-+-H20.

The reactive esters [44;X = H, CO,Et, CN or CH(OEt),] gave34the stable phosphoranes (45) with methylenetriphenylphosphorane, but the vinyl

Ph,P=CHR 3- XC0,Et

/ \

Ph,P=CHCQX

+ EtOH

(45)

(4)R = P h ,

PhCH = CH, or C0,Me

Ph,PO 3- RCH=CX(QEt) (46)

ethers (46) with other phosphoranes. Further examples have appeared36of the reaction of dichloromethylenetriphenylphosphoranewith aroyl cyanides to give 2-aryl-3,3-dichloroacrylonitriles.

0

0

I

0 +Ph,P=CHX (47)

\ I

XCH20CH2X (48) 58 -60%

The bipyrroles (48)were from NN-bisuccinimide and the stable ylides (47; X=CN or C0,Me) under vigorous conditions. Chromium hexacarbonyl and salt-free methylenetriphenylphosphorane gave3' the salt (49) in low yield from which the ylide-carbene complex (50) was obtained on 83 a4

M. Schlosser, D. Coffinet, and H. B. Tuong, unpublished work quoted in reference 32. M. Le Corre, Compt. rend., 1973, 276, C , 963. R. L. Soulen, S. C. Carlson, and F. Lang, J. Org. Chem., 1973, 38, 479. W. Flitsch and H. Peeters, Chem. Ber., 1973, 106, 1731. D. K. Mitchell and W. C. Kaska, J. Organometallic Chem., 1973, 49, C73.

Ylides and Related Compounds Cr(CO), 4- Ph,P=CH,

179 THF

---+

(CO),CrC@)CH=PPh, Ph,$Me (49) 0.3 % k&S02F

(CO),CrC(OMe)CH=PPh (50)

methylation. The tungsten analogue of (49) was obtained similarly but in high yield. MisceZZuneous. Metallation of the acetonylidenephosphorane (31) with butyl-lithium gave38 the anion (51), which with benzophenone and alkyl Ph3P=CHCOMe

BuLi-THF

Ph3P=CHCOCH2 Li+

(31)

(51) hh,CO

Ph 3P=CHCOCHZC(OH)Ph 2

y' Ph,P=CHCOCH,R

(52) 65%

RCHACHC0,Me

(53)

+ Ph,P=CMe, (54)

T

C0,Me

(55) 65-75

+ Ph3P=CHC02Et d 0 'R

(56)

-

%

0 C0,Et

a8--&H--6Ph3

R = HorMe

NC0,-

R

(57)

-co2 -EtOH

J. D. Taylor and J. F. Wolf, J.C.S. Chem. Comm., 1972, 876.

180

OrganophosphorusChemistry

halides gave the expected phosphoranes (52) and (53), respectively. The gem-dimethylcyclopropyl esters (55) were obtained39from ap-unsaturated esters and the isopropylidenephosphorane (54). Isatoic anhydrides and the ester phosphorane (56) gave40 the very stable phosphoranes (58), presumably via the intermediates (57). The synthesis of triazoles from azides and /?-ketoalkylidenephosphoraneshas been extended41 to include iV-vinyltriazoles, Both the triazoles (59) and products derived from the quinquecovalent phosphoranes (60) were obtained42from ester phosphoranes and aryl azides.

(59)

t

ArN,

+ Ph3P=CRC02Et

[

ph~>co2E~ ArN /N

--+Ph,P=NAr

+ [N,CRCO,Et]

k= Ph

JR=Me

(60) EtO,CCMe=CMeCO,Et

A rN= NN= CPhCO ,Et

Attack by methylenetrimethylphosphorane at the 3-position of the silacyclobutanes (61) gave43either the ylide (62; R=Me) or, when R=H, the cyclic ylide (63). Similar ring-opening of the disilacyclobutane (64)gave (65).

+O

Me,P=CH, Me,PhSiHMe

i R , --+ [Me,6(CH2),SiR~~H2J

H*

I ) (63) v

40

'l 4*

'*

4R =

Me,P( :CH,)(CH,),SiR,Me (62)

MeaP=CH, 3- M e , S p S i Me

89

-1

(61)

+

+ Me ,P(:CH,)CH ,Si Me &H,SiMe,

P. A. Grieco and R. S. Finkelhor, Tetrahedron Letters, 1972, 3781. D. T. Connor and M. von Strandtmann, J. Org. Chem., 1973, 38, 1047. P. Ykman, G. Mathys, G. L'Abbk, and G. Smets, J. Org. Chem., 1972,37, 3213. P. Ykman, G. L'Abbk, and G. Smets, Tetrahedron, 1973, 29, 195. H. Schmidbauer and W. Wolf, Angew. Chem. Internat. Edn., 1973, 12, 320.

Ylides and Related Cornpowids Ph3P=CH2

181

+ R1R2CHCH=NA1B~',

20 "C - -

(66)

R1R2C=CHCH=PPh,

(67)

+

Bui,AINH2 (68)

The alkylideneaminoaluminium compounds (66), obtained from diisobutylaluminium and nitriles, with methylenetriphenylphosphorane gaveQQ the allylidenephosphoranes (67), which were isolated by crystallization or used directly, sometimes after precipitation of the aminoaluminium (68) (OC),WC(OMe)Ph

+

Ph,P=CHR (70;

-

R = €1 or Me)

Ph (OC),W-C-OMe

4

WC-PPh,

K LA

PhCOCH,R -+!j$-

RCH=C(OMe)Ph

(711

(72)

by the addition of KNH2. The tungsten-carbene complex (69) with the ylides (70) gave45the vinyl ethers (71), from which the acylbenzenes (72) were obtained in high overall yield after hydrolysis. The carbene complex (73) (OC),WC(OMe)CH,

+ Ph,P=CH2

4

(OC),WC(OMe>cH, P h , k H ,

(73) could not be used in a similar reaction sequence because of proton abstracti~n.~~

2 Phosphoranes of Special Interest The structure of the phosphorane (74), obtained from dichlorophenylphosphine and diethyl malonate in the presence of triethylamine, has been confirmed by X-ray analysis.*' The same technique was used to that the product obtained on heating the adduct (77) of the carbophosphorane (76) and diphenylcarbodi-imidehad the structure (75) and was formed by migration of phenyl from phosphorus to nitrogen. 44 45 46 47 48

B. BogdanoviE. and S. Konstantinovi ', Synthesis, 1972, 481. C. P. Casey and T. J. Burkhardt, J . Amer. Chem. SOC., 1972, 94, 6543. C. P. Casey, S. H. Bertz, and T. J. Burkhardt, Tetrahedron Letters, 1973, 1421. W. Saenger, J. Org. Chem., 1973, 38, 253. F. K. Ross, L. Manojlovic-Muir, W. C. Hamilton, F. Ramirez, and J. F. Pilot, J. Amer. Chem. SOC., 1972, 94, 8739.

Organophosphorids Chemistry

182

(74)

Ph,P=C=PPh,

(75)

+ PhN=C=NPh

I

-+

,yc\. PhN

NPh

Reagents: i, Ph,P; ii, KOBu*; iii, RCHO,

Scheme 4

The 'anti-aromatic' phosphorane (78) was stable only below - 30 "C but reacted norinally with aldehydes (see Scheme 4).49 The deep red-violet phosphorane (79) was stable at room temperature under argon but reacted

(79) S . V. Krivun, 0. F. Voziyanova, and S. N. Baranov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 289.

183

Ylides and Related Compounds

rapidly with oxygen to give the corresponding ketone and phosphine The ylide character of the 2-tropylmethylenephosphoranes(80) was by their normal reactions with aldehydes and with peracids (see Scheme 5).

fl

(80) iib = Me = \

O

M

1

H

e

0

-

0

(81) Reagents: i, BuLi-THF; ii, C,HllCHO.

Scheme 5

The olefin (8 1) was presumably formed via the aldehyde. Therquinquecovalent character of these phosphoranes was shownsa in their Diels-Alder reactions with dimethyl acetylenedicarboxylate and with maleimides (Scheme 6).

(80)

R

+

(MeO,CCi),

= Me or Ph

-

C0,Me

Meo+

P R Ph 3

Ar = p-MeOC,H,

%erne 6 61 62

M. Rabinovitz and A. Gazit, Tetrahedron Letters, 1972, 3361. I. Kawamoto, Y. Sugimura, and Y . Kishida, Tetrahedron Letters, 1973, 577. I . Kawamoto, Y. Sugimura, N. Soma, and Y. Kishida, Chern. Letters, 1972, 931.

184

Organophosphorus Chemistry

Well-defined products are obtaineP3 from trimethylsilylmethylenephosphoranes and ketones only if 'salt-free' ylide is used and the reactants are in the molar ratio of 2:3. Under these conditions the phosphorane (82; K1and R2= Ph) and benzophenone gave quantitative yields of diphenylethylene, tetraphenylallene, bis(trimethylsily1)ether, and phosphine oxide. The reactions involve silyl transfer in the initial adducts (83) and reaction of the resulting ylides (84)with more (82) to give ether and the phosphoranes (85) and (86).

R1,P=CHSiMe, 4- R 2 & 0

Ph,C=CH,

P-

__f

R1,PCH--CR2,

OSiMe,

I

+ Rr3P=CHCR2,

+ Ph,C=C=CPhl + 2Ph3P0

When R1and/or R2are methyi, proton transfer in (86) occurs before reaction with ketone. The cumulene (87) was obtaineds4from an olefin synthesis using propargyltriphenylphosphonium bromide and butyl-lithium as base, presumably uin the cumuleneylide as shown in Scheme 7. The same salt has previously been P h 3 k H & E C H Br- i ,Ph:IP=C=C=CH2

CH=C=C=CH,

56 % Reagents: i, ArCHO dioxan; ii, rri-CIC6H,C0,H.

Scheme 7

to give the expected ene-ynes with conjugated aldehydes in liquid ammonia. Silylation of the terminal acetylenic group also led to normal behaviour in olefin 56 b3 54

55 58

H. Schmidbauer and H. Stiihler, Angcw. Chem. Internat. Edn., 1973, 12, 321. E. J. Corey and R. A. Ruden, Tetrahedron Letters, 1973, 1495. K. Eiter and H. Oediger, Annnlen, 1965, 682, 62. N. N. Belyaev, M. D. Stadnichuk, A. A. Petrov, and A. N. Belyaev, J. Gen. Chem. (U.S.S.R.), 1972, 42, 710.

185

Ylides arid Related Compounds P h , k H , C E C H Br-

+

4-

Ph,P=NN=CHCOR

--+ Ph,PCH,CCH=PPh, Br-

II

NN=CHCOR

(88)

R

.f

I

I

Y

RPh,P

+

CH,

k‘

CH2=C=CH2

RPh,Pf

186

Organophosphorus Chemistry

Reaction of the propargylphosphonium salt with the iminosphosphoranes (88) gaves7 the phosphorane-phosphonium salts (89), which show great potential in heterocyclic synthesis. Thus the salt (89; K=Ph) on heating gave the pyridazine (93), and with sodium ethoxide and p-chlorobenzaldehyde the pyrazole (92) was obtained. Addition of the anilines (90; R = Ph or MeO) to the salt (87) gave the adducts (91), from which the quinolines (94) were obtained on treatment with sodium hydride. The Michael-Wittig reaction sequence, involving the addition of nucleophiles to vinylphosphonium salts and trapping of the resulting ylides, has been extended58 to include substituted vinylphosphonium salts. Among anomalous reactions observed were the formation of the 2-methylbenzopyran (100) instead of the expected 3-methyl isomer when the isopropenylphosphonium salts (95; R = Me or Ph) were fused with sodium salicyloxide (96). The corresponding allylidenephosphoranes (99) are known to give (100) under these conditions and they may have been formed from the betaines (97) either via allene or by rearrangements involving the three-membered phospkoranes (98). In solution (DMF or HMPT) only the 3-methylbenzopyran was obtained. The heterocycle (101) reacted as a methylenephosphorane with both p-nitrobenzaldehyde and diinethyl acetylenedicarboxylate (Scheme 8).59

Ph 2P(:O)N=CMeN=PPh ?.CH=CHC,H,NO ?-p Ph,

+

N-P

Me//

‘\jCO,Mc

Reagents: i, McOLCC1 CC0,Me; ii, p-O2NC6H,CHO.

Scheme 8

67

58 Kg

E. E. Schweizer, C . S. Kim, C. S . Labaw, and W. P. Murray, J.C.S. Chenz. C ’ o r m i . , 1973, 7. E. E. Schweizer, A. T. Wehman, and D. M. Nycz, J. Org. Chem., 1973,38, 1583. R. Appel, R. Kleinstuck, and K.-D. Ziehn, Chem. Ber., 1972, 105, 2476.

Ylides arid Related Compounds

187

The dienes obtainedGofrom the bisphosphonium salt (102) and benzaldehyde with lithium in HMPT or benzophenone with sodium in THF could have been formed via two-electron reduction of the salt to give the bis-ylide or by addition of the carbonyl radical anions as shown in Scheme 9 for I

Ph(CH=CH),Ph

(PhCH0)-' 3- (102)

-

0' I

PhCH

Ph, p

7+\

Ph,

0-

I

PhCH Ph(CH=CH),Ph

Phz

p v+\

t

Reagents: i, PhCHO-Li-HMPT; ii, Ph&O-Na-THF.

Scheme 9

benzaldehyde. Support for the latter route is provided by the formation of diene on reaction of the sodium ketyl from benzophenone with vinyltriphenylphosphonium bromide. Full details have appeared of the preparation and use in olefin syntheses of the salts (103),61(104),62(105),63 and of the salts (106)64 formed by the 4-

Ph ,PCH ,CH,CECSi Me,, 1-

(103) 6u 61

6L

64

Ph$a

Br-

R

( 104) E. Vedets and J. P. Bershas, J. Org. Chem., 1972, 37,2639. A. G . Fallis, M. T. W. Hearn, E. R. H. Jones, V. Thaller, and J. L. Turner, J.C.S. Perkin I , 1973, 743. K. Utimoto, M. Tamura, and K. Sisidoi, Tetrahedron, 1973, 29, 1169. J. A. Eenkhoorn, S. 0. de Silva, and V. Snieckus, Cunad. J. Chem., 1973,51,792. E. Hugl, G . Schulz, and E. Zbiral, Annalen, 1973, 278.

188

OrganophosphorusChemistry

(105)

(106) (Ph3P=CC0 2Me)2Hg

(107) addition of nucleosides and nucleoside bases to p-acylvinylphosphonium salts. Further information has been givens5on the use of the bisphosphorane (107) in the synthesis of divinylmercury compounds. Among other interesting phosphoranes used successfully in olefin synthesis (110),68 and (111),69 and those derived from the salts are (108),66 Ph ,P=CH(CH=kH),CO,Et

a:]

(108)

Ph ,P=CRICO

R?\

Ph&'=CRCOC( :NOH)Ar (109)

Ph,P=CHCOCH,Br (1 11)

Ph,;(CH,)60H I(112)

( I 13)

(1 l2)'O and (1 13).'l The last with &anexcess of paraformaldehyde and ethanolic sodium ethoxide gave 83% of 6-vinyluracil, which could not be obtained by methylenation of or0t aldehyde. 3 Selected Applications of Ylides in Synthesis Natural Products.-The synthetic sequence shown in Scheme 10 was de~eloped'~ in order to elaborate the cephalosporin nucleus (115) from the N. A. Nesmeyanov, A. V. Kalinin, V. S. Petrosyan, and 0. A. Reutov, Bull. Acad. Sci., U.S.S.R., 1972, 21, 1142. M. P. L. Caton, T. Parker, and G. L. Watkins, TetrahedronLetters, 1972, 3341. M. V. Khalaturnik, M. I. Shevchuk, and A. V. Dombrovskii, J. G m . Chem. (U.S.S.R.), 1972, 42, 982. A. S. Antonyuk, M. I. Shevchuk, and A. V. Dombrovskii, J . Gen. Chem. (U.S.S.R.), 1972,42, 1695. Y. A. Zhdanov and L. A. Uzlova, J. Gen. Cliern. (U.S.S.R.), 1972,42, 751. 7 0 R. K. Bentley, E. R. H. Jones, R. A. M. Ross, and V. Thaller, J.C.S. Perkfn I, 1973, 141. '' R. S. Klein and J. J. Fox, J . Org. Chem., 1972, 37, 4381. 7 * R. Scartazzini, H. Peter, H. Bickel, K. Heusler, and R. B. Woodward, Welv. Chim. Acta, 1972, 55, 408.

189

Ylides and Related Compounds R'CONH 0JxHslH20R2

I

4 C HIC 0 , B u '

OH

(114) R2 = COzCHZCC13

C1 Jiii

R 1 C o N ~ s ~ 2 0 H L

gJJNCC0,But

)=PPh,

PPh,

O

II

CO,But

R1coNB3CO,But

Reagents: i, CHO * C02 But; ii, SOCI2-pyridine; iii, PhaP-pyridine; ivy Zii-AcOH ; V, AQO-DMSO.

Scheme 10

t ii

P h 3 C N H ~ ' \COCHtPh 0

Reagents: i, reflux, piperidine; ii, reflux, dioxan.

Scheme 11

yPPh3

190

Organophosphorus Chemislry

p-lactams (1 14) obtained by the degradation of penicillins. Similar sequences were applied to the B-Iactams (116; n = Y 3 or 374)and (117)75(Scheme 11).

(1 18) 4-

Reagents: i, Ph,PCH,OMe CI-, KOBu'; ii, 20% HCI; iii, polyphosphoric acid.

Scheme 12

Dictamnine (118) has been synthe~ized'~ as outlined in Scheme 12 and the general route applied to the syntheses of related furoquinoline alkaloids and of oxaphenalene. The first stage in the synthesis of 'pear ester' involved reaction of hexylidenetriphenylphosphorane with the epoxy-aldehyde (1 19), the major product

(1 19)

15 : 85

being the tra~;l~,cis-isomer.~~ The acetylenic ester (121), prepared by pyrolysis of the P-ketoalkylidenephosphorane(120), was an intermediate in the synthesis78of various naturally occurring sulphur compounds from the family Arctotideae. AcO

QCOCI

AcO

+

Ph,P=CHCO,Me

*

Q

COC(CO,Me)=PPh,

(121) 63 7;

74

76 76 77

'*

R. Scartazzini and H. Bickel, Helu. Chim. A d a , 1972, 55, 423. R. Scartazzini, J. Gosteli, H. Bickel, and R. €3. Woodward, Helv. Chim. Acta, 1972,55, 2567. J. H. C. Nayler, M. J. Pearson, and R. Southgate, J.C.S. Chem. Comm., 1973, 5 8 . N. S. Narasimhan and R. S. Mali, Tetrahedron Letters, 1973, 843. G. Ohloff and M. Pawlak, Heh. Chim. A d a , 1973, 56, 1176. F. Bohlmann and W. Skuballa, Chem. Ber., 1973,106,497.

Ylides and Related Compounds

191

Among many other syntheses involving the use of ylides in key steps are those of the macrolide antibiotic ( k)-pyren~phorin,~~ ( - )-ylangocamphor and related compounds,80isomers of phytoene used in the establishment of its stereochemistry,8la number of polyenes related to carotenoids,82and various crepenyate, linoleate, and oleate esters labelled with 14Cand 3H.s3 Macrocyclic Compounds.-Cyclobutane-1 ,Zdione has been used in the synthesiss4of the interesting thiophen (122) and details have appeared86of

(122) 5 %

the synthesis of the corresponding [6,7]benzo-compound. A reinvestigationa6 of the ylide synthesis of the [12]annulene (123) gave both the &,cis (1.1 %)

(123)

and trans,trans (4.2%) isomers. The conformation of the latter has been determined by X-ray analy~is.~' A number of heteroannulenes have been prepared, some by conventional bisylide reactions, e.g. ( 1 2 4 p and others by construction of cco-diacetylenes

+ (Ph,PCH,),X

2Br(124) X = 0,S, or CH,

8s

84

n6 8a

E. W. Colvin, T. A. Purcell, and R. A. Raphael, J.C.S. Chern. Comm., 1972, 1031. E. Piers, M. B. Geraghty, F. Kido, and M. Soucy, Synthetic Comm., 1973,3,39. N. Khatoon, D. E. Loeber, T. P. Toube, and B. C. L. Weedon, J.C.S. Chern. Comm., 1972,996. E.g. U.S.P.3694491 (Chem. Abs., 1973,78,30033); G. W. Francis, Actu Chem. Scand., 1972,26,2969. G . C . Barley, E. R. H. Jones, V. Thaller, and R. A. Vere Hodge, J.C.S. Perkin 1, 1973, 151. P. J. Garratt and D. N. Nicolaides, J.C.S. Chem. Comm., 1972, 1014. P. J. Garratt and K. P. C. Vollhardt, J. Amer. Chem. SOC.,1972,94, 7087. K. Grohmann, P. D. Howes, R. H. Mitchell, A. Monahan, and F. Sondheimer, J. Org. Chem., 1973, 38, 808. I. Agranat, M. A. Kraus, E. D. Bergmann, P. J. Roberts, and 0. Kennard, Tetrahedron Letters, 1973, 1265. H. Ogawa and N. Shimojo, Tetrahedron Letters, 1972, 4129.

OrganophosphorusChemistry

192

+ (Ph$CH,),S

2Br-

LiO Et

(125) 15%

followed by oxidative cyclization. Among these were the bisdehydrothia[l7]annulene (125),89 the bisdehydroaza[l9]annulene (126; n = l),gOand the analogous [21 Iannulene (126; n = 2).91

Other macrocyclic compounds constructed with the use of ylides included (127)02and (128),93obtained as a mixture of geometrical isomers. Miscellaneous.-Further examples have appeared of the reactions of protected aldehydo- and keto-sugars with simple ylides in conventional olefin syntheses.94 89 O0

91

OP O* Or

R. H. McGirk and F. Sondheimer, Angew. Chem. Internat. Edn., 1972,11, 834. P. J. Beeby and F. Sondheimer, Angew. Chem. Internat. Edn., 1973, 12, 411. P. J. Beeby and F. Sondheimer, Angew. Chem. Internat. Edn., 1973,12,410. H. Ogawa, M. Kudo, and I. Tabushi, Tetrahedron Letters, 1973, 361. W. Carruthers and M. G. Pellatt, J.C.S. Perkin I, 1973, 1136. E.g. J. M. J. Tronchet and J. M. Chalet, Carbohydrate Res., 1972, 24, 263; J. M. J. Tronchet, B. Baehler, H. Eder, N. Le-Hong, F. Perret, J. Poncet, and J.-B. Zumwald, HeZv. Chiin. A d a , 1973, 56, 1310; N. Baggett, J. M. Webster, and N. R. Whitehouse, Carbohydrate Res., 1972, 22, 227.

Ylides and Related Compounds

193

Among polyenes synthesized with the use of ylides were a series of aw-diphenanthrylpolyenesg6and the thiophens (129; n=O, 1, or 2).96 An interesting methylenation was that of the nickel porphyrin complex (130).@'The sequence of reagents shown in Scheme 13 has been usedg8for the 'one-pot' conversion

Reagents: i, Ph,P=CHOMe; ii, H+-H,O; iii, Cr03.

sctrme 13 of adamantanone (1 3 1; R = H) into the carboxylic acid in 70-75 % yield and has also been appliedggto the ester (131 ; R = C0,Me). 4 Selected Applications of Phosphonate Carbanions The diastereoisomers of the p-hydroxyphosphonates (132; R = H or Me) have been obtained.loOTheir behaviour when treated with base demonstrated the direct interconversion of the diastereoisomers (132; R = H) and confirmed the reversibility of the reaction of phosphonate carbanions with carbonyl compounds. This was also shownlolin a study of the p-oxidophosphonateions (133), generated as shown in Scheme 14 from a-cyanovinylphosphonates. Protonation of the p-oxidophosphonate carbanion (134) gavelo2exclusively the less stable diastereoisomer of the p-hydroxyphosphonate (1 35). This contrasts with the protonation of p-oxidoylides, which gives the more stable isomers. Y. Takeuchi, A. Yasuhara, S. Akiyama, and M. Nakagawa, Bull. Chem. SOC.Japan, 1973, 46, 909. G . Manecke and M. Hartel, Chem. Ber., 1973,106, 655. Q' H. J. Callot, Tetrahedron, 1973, 29, 899. O 8 A. H. Alberts, H. Wynberg, and J. Strating, Synthetic Comm., 1972, 2, 79. A. H. Alberts, H. Wynberg, and J. Strating, Tetrahedron Letters, 1973, 543. loo B. Deschamps, G . Lefebvre, and J. Seyden-Penne, Tetrahedron, 1972, 28,4209. l o l D. Danion and R. Carrie, Tetrahedron, 1972, 28,4223. G. Lavielle, M. Carpentier, and P. Savignac, Tetrahedron Letters, 1973, 173. O6

194

Organophosphorus Chemistry (EtO),P( :O)CR(CN)CH(OH)Ph (1 32)

R1R2C=C(CN)P( :O)(OEt),

+

OH- --+

RIR*Ce(CN)P(:O)(OEt),

I

HO

11 R1R2C0 3. cH(CN)P( :O)(OEt),

R'R*CCH(CN)P(:O)(OEt),

I

0(133)

(PriO),P( :O)CHCICH(6)Ar

(PriO),P( :O)CClCH(6)Ar (1 34) p.0

(Pr '0) ,P(:0 ) CHCICH(0H)A c (1 35)

Among phosphonates used in conventional olefin syntheses were (136),lo3 (137),loPand the phosphonates (EtO),P(: O)R1 with R1= CH,(CH: CH),R2,lo5 P( :O)(OPh),

n

(EtO),P( :O)CHRN

WY

(136)Y= O o r C H 2

O,N

@ 0 (137)

CHBrC,H,NOz-p,l,Os or CH,SMe in a synthesisfo7 of ( i)-occidental, CH2SOzR,108CH,SMeR,loSa or CH,NC.loSb The last, with aldehydes in ethanolic sodium cyanide and with acetone in the presence of Cu,O, gave oxazolines. The bisphosphonate (138) gave vinylphosphonates,llO and the H. Bohme, M. Haake, and G . Auterhoff, Arch. Pharm., 1972,305,88. A. Yamaguchi and M. Okazaki, Nippon Kagaku Kaishi, 1973, 110 (Chem. Abs., 1973, 78, 84494). Io5 H. De Koning, A. Springer-Fidder, M. J. Moslenaar, and H. 0. Huisman, Rec. Trau. chim., 1973, 92, 237; H. De Koning, G . N. Mallo, A. Springer-Fidder, K. E. C. Subramanian-Erhart, and H. 0. Huisman, ibid., p. 683. Io6 A. Yamaguchi and M. Okazaki, Nippon Kagaku Kaishi, 1972,2103 (Chem. Abs., 1973, 78, 29372). l o * D. S. Watt and E. J. Corey, Tetrahedron Letters, 1972, 4651. l o 8 G. H. Posner and D. J. Brunelle, J. Org. Chem., 1972, 37, 3547. l o S (a) K. Kondo and D. Tunemoto, J.C.S. Chem. Comm., 1972,952; (b) U. Schollkopf and R. Schroder, Tetrahedron Letters, 1973, 633. ' l o W. F. Gilmore and J. W. Huber, tert., J. Org. Chem., 1973, 38, 1423.

loa

lo*

195

Ylides and Related Compounds [(EtO),P(:O)CH,I*P(:O)OEt

+ RCHO

NaH

-:RCH=CHP( :O)(OEt),

+ (EtO)zP( :O)CH,P(O,-)OEt

(138)

carbanion from the diazophosphonate (1 39) with carbonyl compounds gave acetylenes,lll probably formed uia rearrangement of the intermediates (140). BuLi-THF

(MeO),P( :O)CHN

(MeO),P(:O)CN,

____f

-80 "C

(139)

The dianion (142), formed on treatment of the phosphonate carbanion (141) with butyl-lithium, alkylated exclusively on the y-carbon with alkyl

(Ma),P( :O)eHCOCH,

(MeO),P( :O ) ~ H C O ~ H ,

BuLi

(141)

(1 42)

.1=

(MeO),P( :O)CM,COCH,R

xsiMe3

PhCOO P

h

C

Y

Ph

Me,SiCHP( :O)(OEt), hC0,Me

(143)

\p, [PhCOCH(SiMe3)P(:O)(OEt),]

PhCoNMezl

Me,Si-CHP( :O)(OEt),

1

-0-CPhNMe

Me3SiO-

-1

P(:O)(OEt),

(144)

+ PhC(NMe,)==CHP(:O)(OEt),

(145)

I PhCOCH,P(:O)(OEt), (146)

(147) 24%

halides.l12 With benzoyl chloride the phosphonate carbanion (143) gave118 the O-benzoylated product (144) of the expected phosphonate (145), but 118

lIS

E. W. Colvin and B. J. Hamill, J.C.S. Chem. Comm., 1973, 151. P. A. Grieco and C. S. Pogonowski, J. Amer. Chem. SOC.,1973, 95, 3071. F. A. Carey and A. S. Court,J. Org. Chem., 1972, 37,939.

196

Organophosphorus Chemistry

with methyl benzoate the phenacylphosphonate(146) was formed, presumably via desilylation of (145). With NN-dimethylbenzamide and (143) the vinylphosphonate (147) was obtained. To overcome the lack of reactivity of long-chain aldehydes towards the ester carbanion (148), this was acylated and the resulting 8-ketophosphonates reduced and then treated with base as in Scheme 15.114 trans-@-Unsaturated EtO,CCHP(:OXOEt),

A

RCOCH(CO,Et)P(:O)(OEt),

(148)

Jii

RCH(OH)CH(CO,Et)P( :O)(OEt) 2 tii

RCH=CHCO,Et Reagents: i, RCOCl; ii, NaBH, or H,-Pd; iii, NaOEt.

Scheme 15

ester was obtained irrespective of the isomer composition of the intermediate 8-hydroxyphosphonate. The nitrile-phosphorme carbanion (149), generated (EtO),P( :O)cHCN

ArCNO

(149)

(1 50) 25-3 1 %

H,W -P(:O)(OEt),

n

ArN,N9N

(151) 54-81

%

in ethanolic sodium ethoxide, with benzonitrile oxides gave the oxazoles (150) and with aryl azides the triazoles (151).l15Under the same conditions the ester carbanion (148) with aryl azides gave the diazophosphonates (152), and

(148)

+ ArN,

[

HO- P(:O)(OEt), ArNQN

]

--+ ArNHCOCN,P(:O)(OEt),

(1 52)

mixtures of the triazoles (154) and (155) were obtained from the carbanion (153) and aryl azides. 11* 116

G. Durrant and J. K. Sutherland, J.C.S. Perkin I, 1972, 2582. U. Heep, Annalen, 1973, 578.

197

Ylides and Related Compounds

PhCOCHP(:O)(OEt),

-

+ ArN,

(153)

0 P(:O)(OEt), PhftH

Ph/,\P( /N w-

ArN

ArN

:O)(OEt) 2

/N

' I 4

(154)

(155)

The formation of cyclopropanes from epoxides and the carbanion (148) has been shown to involve inversion of configuration at both carbon atoms.116 Terminal epoxides with the phosphonates (156) gave trans-cyclopr~panes.~~~

~

1

8

aF

f1 (EtO)2P(:O)CH2COCHONRa2

2NR'2

5 Ylide Aspects of Iminophosphoranes

Details have appearedlls of the formation of N-styryliminophosphoranesfrom the reactions of 2H-azirines with triphenylphosphine and tetrahalogenomethanes, e.g. (158) from (157). Besides the expected carbodi-imides, the

ArF?co2R

PhaP= C&

Ph,P=NCArl=C(CN)C,H,R-p

Ph,P=NCAr=CXCO *R

+ Ar2NC0

(1 59)

-

Ar*N=C=NCAr1=C(CN)CBH4R-p + NHArZ

Ar2

(161) lla 118

R. A. Izydore and R. G. Ghirardelli, J. Org. Chem., 1973, 38, 1790. M. Baboulene and G. Sturtz, Phosphorus, 1973,2, 195. T. Nishiwaki and F. Fujiyama, J.C.S. Perkin I, 1973, 817.

198

Organophospkorus Chemistry

isoquinolines (160) were obtained from the reactions of the iminophosphoranes (1 59) with aryl isocyanates. The carbodi-imides were not intermediates in the formation of (160) and cyclization of the initial adducts (161) was suggested. R *P(:NAr)OCH*C6H,WO 2-p (163) R2:27Ar R *P(:NAr)OCHPhCOPh

But (1 65)

But (166) 71-78%

The iminophosphoranes (1 63) and (164) were obtainedllDfrom the aminophosphines (162; R1= Ph or OR2) and p-nitrobenzaldehyde and benzil, respectively. The reactions presumably involve initial attack of the phosphines on carbonyl oxygen followed by proton transfer. Pyrolysis of the imines (165) gave the cyclic iminophosphoranes (1 66) and arene.120 The results of a kinetic investigation of the reactions of the iminophosphoranes R,P=NPh with p-nitrobenzaldehyde in various solvents were held121to be inconsistent with the formation of betaine intermediates. Instead the direct formation of four-membered covalent adducts was suggested.

The iminophosphoranes (1 67 ; R1= alkyl or aryl) with acyl halides gave122 the imidoyl halides (168 ; X = C1, Br, or I), whereas (167 ; R1= SiMe,) with A. N. Pudovik, E. S. Batyeva, and V. D. Nesterenko, Bull. Acad. Sci., U.S.S.R.,1972, 21,825; A. N. Pudovik, E. S. Batyeva, V. D. Nesterenko, and N. P. Anoshina, Sbornik Nekot. Probl. Org. Khim., Mater. Nauch. Sess., Inst. Org. Fiz. Khim., Akad. Nauk S.S.S.R.,1972,6 (Chem. Abs., 1973, 78, 29909). l a 0 H. B. Stegmann and G. Bauer, Synthesis, 1973, 162. lS1 P. Frsyen, Acta Chem. Scand., 1972, 26, 1777. E. Zbiral and E. Bauer, Fhosphorus, 1972, 2, 35.

11'

199

Ylides and Related Compounds

both acyl halides and acid anhydrides gave the acyliminophosphoranes (1 69).123The N-lithioiminophosphorane (170) has been treated with chloroand dichloro-disilanes to give a series of disilanyl-substituted amines, e.g. (171).124

Me,P=NLi

+

Me,Si,CI,

+ [Me,P=NSiMe,], (171)

(170) Ph3P=NNH,

% :- :

Ph,PO

+

N,

(172)

Oxidation of the aminoiminophosphorane (1 72) with mercuric oxide gave phosphine oxide and nitrogen,126but attempts to trap the supposed intermediate Ph3PN2were unsuccessful.

H. R. Kricheldorf, Synthesis, 1972, 695. H. Schmidbauer and W. Vornberger, Ckem. Ber., 1972,105, 3187. l a bK. Yamada and N. Inamoto, Bull. Ckem. SOC. Japan, 1972,45, 1559. l** 1*4

9 Phosphazenes BY R. KEAT

1 Introduction The past year has been notable for the number of reviews related to this topic. The most important of these is a monograph,l which gives an excellent comprehensive coverage of phosphazene chemistry, although it might disappoint those interested in the more general aspects of phosphorus-nitrogen chemistry, coverage of which is implied by the title. The same author has also given a review of recent developments in this field. Cyclophosphazene chemistry is covered in a new biannual review s e r i e ~and , ~ analytical aspects of this topic have been s ~ r v e y e dThe . ~ chemistry of linear halogenophosphazenes5 and trihalogenomonophosphazenes has been reviewed. The latter two reviews contain a useful collection of data from the extensive literature on this topic originating in the Soviet Union. 6s

2 Synthesis of Acyclic Phosphazenes From Amides and Phosphorus(v) Halides.-Surprisingly few examples of the Kirsanov reaction have been reported, and in most of these the formation of a phosphazene, X3P=NR, was accompanied by halogenation of the R group. For example, adipamide and phosphorus pentachlorideundergo the reaction :8

In this case it appears that chlorination of the keto- and methylene-groups is preceded by the formation of the -N=PC13 group. Previous observations concerning the formation of a dinitrile from the same reaction, but in the absence of a solvent, were also confirmed: PCI

H2N.CO(CH2)4CO-NH2-i&+ NC(CH,),CN

+

decomposition products

H. R. Allcock, ‘Phosphorus-Nitrogen Compounds’, Academic, New York, 1972. H. R. Allcock, Chem. Rev., 1972,72, 315. * D. B. Sowerby, in ‘MTP International Review of Science, Inorganic Chemistry, Series One’, ed. C. C. Addison and D. B. Sowerby, Butterworths, London, 1973, Vol. 2. J. M. E. Goldschmidt, in ‘Analytical Chemistry of Phosphorus Compounds’, ed. M. Halmann, Interscience, New York, 1972, p. 523. H. W. Roesky, Chem.-Ztg., 1972,96,487. a M. Bermann, Adu. Znorg. Chem. Radiochem., 1972, 14, 1. M. Bermann, Topics Phosphorus Chem., 1972, 7 , 31 1. H. A. Klein and H. P. Latscha, 2.anorg. Chem., 1973,396,261.

200

Phosphazenes

201

Hydroxy-groups in the side-chain R2 of the acetimides R1C(=NR2)NH2 are chlorinated when phosphazenylation of the NH2 group is effected by phosphorus pentachl~ride.~ Phosphinothioylamines are desulphurated by phosphorus(v) chlorides:lo

+

R1R2*P(S)*NH2 2R3PC1,

R1

+

R1RZ*P(S).NH2 2R3R4PC13

__f

R3

-i-

[ g; ] C1-

I =N-P-CI

CI-

+

R3R'P(S)CI

k 4

(Rl, R2, R3, and R4 included Me, Et, and Ph)

The reactions of these phosphazenyl derivatives are typified by that of [R1R2PCl=N.PR3C12]+CI-, which gave [(H2N)R1R2P=N.PR3(NH2)2]fC1-, R1R2PCI=N.PR3(0)CI, and R1R2P(OH)=N.P(0)R3(0H), on reaction with ammonia, sulphur dioxide, and formic acid, respectively. Perfluoroalkyl- and other halogenoalkyl-carboxylic acid amides have also been employed as substrates for somewhat modified Kirsanov reactions:ll. l 2

R*CO*NH2 + 2PhPF4 3. 2EtaN

4

R*CO*N=PF2Ph+ 2Eta&H PhPF5-

(R = CF3or n-C3F,; ref. €1) R*CO.NH, + 2PC15

R*CCI,*N=PC13

(R = CHBr,, ClCH,.CHCl, or ClCH,.CCI,; ref. 12)

Phosphazenes of the type C13P=NR generally give dichlorophosphinylamides, RNH.P(0)C12, on reaction with formic acid, but the latter series of halogenoalkyl derivatives gave N-phosphinylimides, RCCl[=N P(O)Cl,] with this reagent.12 The reaction of phosphorus pentachloride with ammonium chloride in the presence of boron trichloride leads to the formation of chlorophosphazonium V. P. Rudavskii and M. N. Kucherova, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1283. A. Schmidpeter, N. Schindler, and H. Eiletz, Synth. Inorg. Metal-org. Chem., 1972, 2, 187. 1 1 G. Czieslik and 0. Glemser, Z . anorg. Chem., 1972, 394, 26. 1% V. P. Rudavskii and D. M. Zagnibeda, Farm. Zhur. (Kieu), 1972, 27, 35. 0

10

202

Organophosphorus Chemistry

tetrachloroborates, [CI(CI,P= N)12PC13]+ BC14-, rather than to products containing boron-nitrogen bonds.13 The degree of condensation, n, was shown by 31P and llB n.m.r. to be dependent on the temperature employed; thus at 75 "C in dichloroethane n is mainly 1, with some 2, but at ca. 130 "C products with n = 2,3, and higher values have been identified. Similar products were obtained from PCI4+BC1,- and ammonium chloride. Interesting new N-trimethylsilylphosphazeneswith considerable synthetic potential have been obtained from the lithio-derivative LiN(SiMe,), :14,l6 PC15

+ LiN(SiMe&

POC13

+ LiN(SiMe,),

-

C13P=N.SiMe3 .(Me,SiO)CI,P=N~SiMe,

(ref. 14) (ref. 15)

The latter monophosphazene, which may also be obtained in an impure form from the reaction of phosphoryl(v) chloride with N(SiMe&, is obviously isomeric with ClzP(0).N(SiMe3)2and is presumably formed partly as a result of the tendency of silyl groups to bond to oxygen where possible. It is worth noting, however, that the analogous fluoride F,P(O) .N(SiMe,), does not exist in the phosphazene form, so that the tautomer obtained reflects a rather subtle balance of electronic factors. From hides and Phosphorus(m)Compounds.-This class of reaction continues to provide a convenient route to a wide range of novel monophosphazenes. For example, 1,2,5-triphenylphosphole(1) eliminates nitrogen with the azides

RN, (R = Ar, ArSO,, MeS02, Et02C, or Ph,PO) to give the phosphazenes (2).16 The products were all thermally stable except for when R = o-nitrophenyl, which gave the analogous phosphole oxide and benzofurazan (3) on heating. The phosphite (4) may be converted into a phosphazene (3, with complete retention of configuration at phosphorus, on reaction with phenyl a2ide.l' This was deduced from the sequence of reactions shown in Scheme 1. Nucleoside 5 '-phosphite esters have been derivatized as monophosphazenes by reaction with phosphinyl and sulphonyl azides, and the aminophosphite la

l4

l6 l6 lq

lS

K. Niedenzu, I. A. Boenig, and E. B. Bradley, Z . anorg. Chem., 1972,393,88. E. Niecke and W. Bitter, Inorg. Nuclear Chem. Letters, 1973, 9, 127. G. Czieslik, G . Flaskerud, R. Hofer, and 0. Glemser, Chem. Ber., 1973, 106,399. J. I. G. Cadogan, R. Gee, and R. J. Scott, J.C.S. Chem. Comm., 1972, 1242. W. Stec and A. kopusiniki, Tetrahedron, 1973, 29, 547. G. Baschang and V. Kvita, Angew. Chem. Internat. Edn., 1973, 12,70.

Phosphazenes

203

Scheme 1

(MeO),P.N(SiMe,), eliminates nitrogen to give (7) on reaction l9 with trimethylsilyl azide at ca. 110 “C.The two trimethylsilyl signals in the lH n.m.r. spectrum of (7) coalesce at 98 “C,probably as the result of an intramolecular 1,3 trimethylsilyl group shift involving an intermediate of the type (8).

WesW2N, (MeO)2P*N(SiMe3),4- Me,SiN, -+

MeOTP=N-SiMe, Me0

SiMe, I

Me0 N \ / \ P:+ -SiMes

M&/ \.N/ I

%Me,

l8

0.J. Scherer and R. Thalacker, 2.Nuturforsch., 1972, 27b, 1249.

+ N2

204

Organophosphorus Chemistry

The azide synthesis has been used to advantage in the formation20of (9), a derivative which could not be obtained by the elimination of trimethylsilyl chloride between the urea derivative, [(Me,Si)MeN],CO, and PhN= PCI,NEt,. The feasibility of stepwise reactions between diphosphines and azides has The reaction of the tellurium azide been demonstrated, e.g. Scheme Cl,TeN, with triphenylphosphine does not result in the formation of a phosphazenyl-tellurium derivative (Scheme 3). 2 2 This is probably a result of the tendency of the Te-N bond to heterolyse (Scheme 4).

PhN=PYh

2

CH2*PhZP=NPh

Scheme 2

2CI,TeN,

+ 4Ph,P

__f

2[Ph3P-N=PPh,]+TeC1,2-

+ Te + 2N2

Scheme 3

CI,Te-N=N=N

+ Ph3P

-+

[CI,Te-N=N-N=PPh,] .e

C1,Te- 4- N=N=N-PPh,

Scheme 4

Phosphazenes fail to result from the reaction of acyl azides and phosphorus tri-i~ocyanate,~~ which gives instead a uretidinedione (Scheme 5). It is worth noting here that azides and ethoxycarbonylalkylidenetriphenylphosphormes, R0,C -CH=PPh3, form pho~phazenes;~~ this reaction is discussed further in Chapter 8. 30

$1

st a* 94

M. Bermann and J. R. Van Wazer, J.C.S. Dalton, 1973, 813. V. Yu. Kovtun, V. A. Gilyarov, and M. I. Kabachnik, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 2612. N. Wiberg, G. Schwenk, and K. H. Schmid, Chem. Ber., 1972, 105, 1209. E. S. Gubnitskaya and G. I. Derkach, J. Gen. Chem. (U.S.S.R.), 1972, 42, 287. P. Ykman, G. L'Abb6, and G. Smets, Tetrahedron, 1973, 29, 195.

Phosphazenes

205

0

Scheme 5

Other Methods.-The synthesis of monophosphazenes from the reaction of nitriles with phosphorus pentachloride continues to be studied. With benzcitri rile,^^ as with acetonitrile, the products depend on the molar ratios of reactants and with three molar equivalents of phosphorus pentachloride the reaction is: PhCHZ.CN

+ 3PCIb

PhCCIy*CCI,N=-PCI3

With smaller proportions of phosphorus pentachloride, the olefmic deriva-

ph,

,c=c,

H

Cl

Ph,

/

N=PCI,

Cl

C=C

0

h=PCI3

C’l (1 1)

(10)

tives (10) and (11) are formed. PhCCl, CCl, .N=PCI, undergoes expected reactions with formic acid and with boron trifluoride: HCQ2H/

PhCCli C(CI)=N* P(O)C12

PhCCI,* CCIZ*N=PCI, BFh

PhCCl,.CCl,.N(~F,)i;Cl,

Bis(dipheny1phosphino)amines 2 6 and bis(dipheny1phosphino)methane 2 7 have both been utilized as substrates for condensation with ammonia and carbon tetrachloride (Scheme 6) (similar reactions have been carried out with HN(PPh,),

+ CCIJ +

H2C(PPh2), + CCIJ

NH,

+ NH3

-+

[H2NPh2P-NqPh2NH2]+C1[H2NPh2P-N=PMePh,]+Ci-

Scheme 6 p K

za 37

E. Fluck and W. Steck, Phosphorus, 1972, 1, 283. R. Appel and G. Saleh, Annalen, 1972, 766, 98. R. Appel, R. Kleinstiick, and K.-D. Ziehn, Chem. Ber., 1972, 105, 2476.

206

L)i~~aiiopliosphouus Chemistry

t-butylamine and phenylhydrazine in the presence of triethylamine). It was suggested that the latter salt is formed by the mechanism shown in Scheme 7.

Ph H2NPhzP-N=PMePh2

f--

H Phz H,N

Scheme 7

When more than one methylene group bridges the diphenylphosphinogroups, cyclic products are obtained (Scheme 8).

Scheme 8

A closely related method has also been used for the synthesis of cyclic phosphazenes (see Section 5). Interesting possibilities are also suggested by the reaction 38 of phosphines with N-chlorohexamethyldisilazane:

(X = Alk, Ar, or OAlk) By analogy with the reactioiis of N-chlorodialkylamines with phosphines, zB

A. M. Pinchuk, M. G. Suleimanova, and L. P. Filonenko, J . Gen. Chem. (U.S.S.R.), 1972, 42, 2111.

207

Phosphazenes

+

which give stable phosphonium salts R1,N .PR,Cl-, it was suggested that the

+

disilazane reaction proceeds uiu salts of the type (Me,Si),N.PR, C1-. Benzil and (EtO),P .NHPh give the thermally unstable phosphazene (EtO),P( :NPh)OCH(Ph)CH,Ph in diethyl ether solution.29 3 Properties of Acyclic Phosphazenes Halogeno-derivatives.-The alcoholysis30 of the diphosphazene C1,P =NCI,P=N-P(S)Cl, follows a course similar to that observed last year for CIF,P=N .P(S)F, in that a thioalkoxy- rather than an alkoxy-derivative is obtained :

(R = MeorEt)

Initial nucleophilic attack by the alcohol probably occurs at the CI,P=Ngroup, and the product rearranges to the thioalkoxy-derivative by an intramolecular exchange process. The triphosphazene Cl(Cl,P= hT)3P(0)C12 has also been alcoholized: C1(C1,P=N)3P(0)C12

ROH- Et3N +

HO [(RO) aP=N] ,P(O)(OR) 3.

(R = A l k o r A r )

Although the product is represented here as a hydroxyphosphazene, there is infrared evidence that this product is in equilibrium with its tautomer:

Alkyl chlorides were eliminated when the alkoxy-derivativeswere heated with triphenylsilyl chloride, and it was shown that silyloxy-groups are introduced at both terminal and bridging phosphorus atoms :

Thermal decomposition of the N-sulphonyl phosphazenes CIR2P= N * S0,X (R = Cl, Me, or Ph; X = F or C1) results32in the formation of phosphinyl chlorides, R,P(O)Cl, and oligomers of the type [NS(O)XIn, rather than the 29

30

31

32

A. N. Pudovik, E. S. Batyeva, and V. D. Nesterenko, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 871. H. W. Roesky, Z . Nrtturforsch., 1972, 27b, 1569. A. A. Volodin, V. V. Kireev, V. V. Korshak, and E. A. Filippov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 509. W. Naubold, E. Fluck, and M. Becke-Goehring, 2. anorg. Chem., 1973, 397, 269.

208

Organophosphorus Chemistry

phosphazenes (R2PN)nand the sulphuryl chlorides S02C1X. The ring compound (12) was obtained in 20% yield from the thermolysis products of C13P= N - S02C1. When compounds containing longer phosphazene chains were pyrolysed the range of products was more complex, as might be expected, e.g. Scheme 9. Both Cl,P=N - C(C1)= N - Cl,P= N S0,Cl and (CI3P=N)2-

(13)

Scheme 9 C=N.Cl,P=N -SO,CI gave phosphoryl chloride, C13P=N -SO,CI, and other unidentified products, whereas SO,(N= PCl, .N=PCI,), gave CI,P=NP(0)Cl2 and (14). Almost identical results for the decomposition of CI,P=N-Cl,P=N .S02C1have been reported by other workers,33who found that the preparation of (14), which was first reported last year, is best achieved by heating Cl,P=N.SO,Cl and Cl(Cl,P=N),SO,Cl in a 1 : 3 molar ratio, respectively. The infrared spectra of (12), (13), and (14) were also discussed. Thermal methods were also employed in the synthesis3.*of the novel cage compound (1 5) from the dimeric phosphazene (MeNPF3),. The formation of

(15) in a bomb at 130 "Cwas accompanied by the appearance of a salt formulated as (16), insoluble in carbon tetrachloride, which gave (17) on vacuum sublimation. An n.q.r. study 3 5 of the dimeric phosphazenes (1 8 ; R = Me, Et, or Ph) showed that the axial and equatorial chlorine atoms are readily ss

H. H. Baalmann, H. P. Velvis, and J. C . van de Grampel, REC.Trau. chin?., 1972,91,935. K. Utvary and W. Czysch, Monatsh., 1972, 103, 1048. R. Keat, A. L. Porte, D. A. Tong, and R. A. Shaw, J.C.S. Dalton, 1972, 1648.

209

Fhosphazenes .C1

distinguished, with the latter giving the higher-frequency signal, implying the least ionic character. Although it is well established that the foregoing dimeric phosphazenes contain a four-membered ring, the structures of dimeric N-cyanoalkylphosphazenes, WC(Alk),C .NPCl,],, are not necessarily similar 36 because the bulky N-substituent may well inhibit the formation of a ring analogous to that in (18). The N-cyanoalkyl dimers readily add hydrogen chloride to give compounds of structure (19), and in view of this it was suggested that the dimers have CIC-CAlk, II I N,+NH

CI-

structure (20), where the steric effects of the N-substituent may offer less restraint to dimer formation. This is consistent with the fact that absorptions characteristic of C = N and P-N are present in the infrared spectrum of (20). The N-chlorophosphazene (Cl,C),CIP= NCI can be obtained 37 by the route: (C13C),ClP--IUH i- Clz

pyridine:

(CI,C)2ClP=NCI

and is sufficiently thermally stable to be vacuum distilled. It undergocs a number of interesting reactions, which are summarized in Scheme 10. The infrared identification of the vibrational modes associated with the P-N bonds in these derivatives was also discussed. (C1,C),CIP=N

*

C1

pi>

(Cl ,C),ClP=N* PCI,

""*

(C13C),ClP(O)NH,

PCI,

*

(C1,C),CIP(O) N=PCI

3

(Cl,C)2CIP=N* P(0)Cl Scheme 10

aa

A. M. Yinchuk, I. M. Kosinskaya, and V. I. Shevchenko, 3. Gem. Chem. (U.S.S.R.), 1972, 42, 520. E. S. Kozlov and S. N. Gaidamaka, J. Gem Chem. (U.S.S.R.), 1972, 42, 101.

Organophosphorirs Chemistry

210

N-(Chloroalky1)phosphazenes behave 38 like aa-dihalogenoamines in forming adducts with Lewis acids: RCIZC. CIZC. N-PCI,

+

MCI,

--+

[RCItC * CIC=N* PCI,]-' MCIG+,

(MCln included AlCI'3,SbCI,, and FeCl,),

These adducts are extremely electrophilic and readily react with water, or even weakly basic organic compounds, for example, benzene: [C1,C*CIC=N*PCIJ+ SbClG- -I- PhH --+

[Cl,C*ClC(Ph)N=PCl3]SbCI,

The conditions required for the reaction of C13C- C1,C .N =PC13with benzene in the presence of Lewis acids have been studied in and several aryl trichloromethyl ketones have been synthesized by hydrolysis of the complexes formed : ArCO. CCI,

C1,C.ClCAr.N=PCl,.MCI,,

P-Bis(t-buty1dioxy)phosphazenes have been prepared 4o by the route : RN=PCI,Ph

+

2 NaOOBut

_j_

RN=PPh(OOBut),

(R = substituted vinyl group4oor ArSO,*l)

and their hydrolysis and acidolysis followed in detail. Predictable results 4 2 have been observed in the aminolysis, alcoholysis, and thioalcoholysis of N-(monofluoropheny1)phosphazenes : ArCO*N=PCI,

+ RNHz --+

ArCO.N=PCl,

+ XH

Et,N

Aikyl and Aryl Derivatives.-The 38

*

ArCO.N=P(NHR),

+ &H3RC1-

ArC0.N=PX3

N-lithiated phosphazene Me3P=NLi

V. P. Kukhar', V. Ya. Sernenii and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 93.

40

V. P. Kukhar', A. P. Boiko, L. A. Zolotareva, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 270. A. G. Babyak, T. I. Yurzhenko, and N. D. Bodnarchuk, J. Gen. Clzem. (U.S.S.R.), 1972, 42, 533.

41

42

A. G . Babyak and T. I. Yurzhenko, J. Cen. Chem. (U.S.S.R.) 1972, 42, 529. V. P. Rudavskii, L. N. Sedlova, and M. N. Kucherova, J. Gen. Chem. (U.S.S.R.), 1972, 42,961

21 1

Plz ospliazenes

condenses with niethylchlorodisilanes in ether solution at ambient temperatures 4 3 to give N-disilanylphosphazenes: Mc,P=NLi

-t- McjSi,CI

2 Me,P=NLi

+ MelSi,C1,

-+

Me3P=N.Si,Me,

-* Me3P=N*SiMe2*SiMe,.N=PMe3

A disilane terminated by a methylenephosphorane as well as by a phosphazene was also synthesized (Scheme 11). There was no evidence from infrared and IH 1i.m.r. spectroscopy that conjugative effects could be transmitted from in these systems. nitrogen to a P-silicon atom (i.e. N-Si-Si) Me,Si2CI,

- Me,Si ,c, * Me ,P =N - Si Me Si Me ,C1

Me ,P=N Si Me Si Me

Me,P=CH,

/, -

Me,PCl

Me3P=N * Si Me Si Me - CH =PMe, *

Scheme11 The cleavage of silicon-nitrogen bonds in N-silylphosphazenes has also been accomplished44by PF5 and by PhPF,: 2 Ph3P=N.SiMe,

+ 2 RPF,

+

(R = F o r P h )

Suitable modification of the proportions of the reactants has enabled monophosphazeiiyl derivatives to be obtained also : R1,R2P=N-SiMc, + 2 PhPF, --+ [K',R'P=N.PPhF',I+[PhPF,]- + Me,SiF (R1

= R' = P h ; R 1 =

Me,Rz = ph)

N-Sulphinylphosphazenes form the subject of a patent application 4 5 and were synthesized by a simple condensation reaction : Ph,P=NH

+ p-RC,H4*SOCl +

Et,N + Ph,P=N.SO*CGH,R-/)

+ E t , i H C1-

(R = H'or Me)

The hydrolysis of N-sulphonylphosphazenes, Ar,P= N * SO, - C,H,Me-p obtained from the long established reaction of phosphines with chloramine-T, Is 44

H. Schmidbauer and W. Vornberger, Chem. Ber., 1972,105, 3187. R. Appel, I. Ruppert, and F. Knoll, Chem. Ber., 1972, 105, 2492. A. D. Josey, U.S.P. 3 647 856 (Chern. A h . , 1972,76, 141 023).

Organophosphorus Ciierriistry

21 2

results 4 6 in the formation of hydrogen-bonded adducts of the type formulated in structure (21).

91)

The factors affecting the formation of imines from the arylphosphazenes Ar1,P-NAr2 and aldehydes by a route analogous to the Wittig reaction have been examined further.47 Studies of the auxochomic action of the triarylphosphazenyl group, Ar,P=N-, have entailed the synthesis4* of an extensive range of azocompounds, Ar1Ar2Ar3P=N.CsH4-p-N=N.C6H4R, in which variation of the electron-donor properties of the Ar groups has but a marginal effect4'J on the parts of the electronic spectra associated with the azo-function. It is interesting that the Ph,P=CH- group is a better electron donor than the isoelectronic phosphazenyl group, P$P= N-,50 according to comparisons based on the electronic spectra of the azo-compounds Ph3P=X-C6H4-N=NC6H4R( X = N or CH), a finding that may be contrasted with the fact that the following phosphonium salts may be deprotonated by Ph,P=NH: e

I~h,P-CH,-C,l I,.N=N.C6H,R Br- -1- Ph3P=NH

-+

Ph ,P=CM*C,H4*N=N*C ,H i R

+

P ti ,,F"H Hr-

Hammett 0- constants have been calculated51for the K group in the azocompounds RCsHp.N=N.C6H4QM,from the results of titration of these weak acids with base. The CT- constant for the Ph,P=N- group was very similar to that of the NH2 or NMe, groups, 2s might have been expected from previous studies. Related results have been obtained 5 2 for compounds of the type Ar1Ar2Ar3P=N- C6H4K,in which features of the electronic spectra were related to o+ and 0- constants for the substituents in the Ar groups. The electronic spectra of the phosphazenes p-Q2NCGH4Ph,P=NCGH4K-p (R = H, NO2, or NMe,) have been The tautomeric equilibrium : t

1'1 ,P=N. CGH 1 * N=N H CG HJX

I

F?

Ph,%P--NI 1* C6H,*N=N CGH,X

D. W. Allen, F. G . Mann, and J. C . Tebby, J.C.S. Perkiti I , 1972, 2793. S. C. K. Wong and A. W. Johnson, J. Org. Chem., 1972, 37, 1850. I. N. Zhmurova, V. G. Yurchenko, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1938.

I. N. Zhmurova, V. G . Yurchenko, A. P. Martynyuk, and A. V. Kirsanov, J. Gerr. Chcm. (U.S.S.R.), 1972, 42, 1942. R. I. Yurchenko, I. N. Zhmurova, L. N. Shpartun, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.),1972, 42, 2350.

Phosphazenes

213

lies to the left when X = NOz, but is shifted well to the right with most other X s ~ b s t i t u e n t s .Different ~~ results were obtained for the azo-compounds Me2N-C6H4.N=N.C6H4X, which were protonated at the azo-group rather than at the dimethylamino-group. Measurements of pKa values of compounds of the type R1C6H4-CH=N.C6H4R2 indicate 55 that protonation occurs at the azomethine nitrogen atom when R1 = NMe,, but at the phosphazenyl nitrogen atom when R1 = N=PPh,. Molecular orbital calculations have been carried out 56 on monophosphazenes of the type R1,P=NR2, and the results related to the data obtained from electronic and infrared spectra. N-Phenyl-PPP-triphenylphosphazene, Ph,P=NPh, forms5’ a radical species on reaction with sodium dispersed in THF which shows clearly resolved hyperfine coupling to 14N and 31P nuclei, although it was not clear whether the radical present was the anion: Ph,P-A--Ph,

Ph,P-R-Ph

or the neutral species:

=+=

PhzP-N-Ph

PhZP-N-Ph

formed by elimination of phenylsodium. ESCA determination58 of nitrogen 1s and phosphorus 2p binding energies in salts of the type [Ph,P-N-PPh,]+ +

-

+

X- suggests that the cation is better represented as [Ph,P-N-PPh3]

+

rather

than [Ph,P=N=PPh,]. The two types of phosphorus atom in the N-diphenylphosphinylphosphazene Ph,P= N P(O)Ph, could not be distinguished by their 2p binding energies, also obtained 59 by ESCA. 6

4 Synthesis of Cyclic Phosphazenes Further examples6o of monophosphazenes which form part of a five-membered ring have been synthesized from N-phosphinoimines and electrophilic olefins in a 1,3-cycloadditionreaction (Scheme 12). The lH and 31Pn.m.r. spectra of these derivatives show that the tautomeric equilibrium in Scheme 13 lies 61

6a

68 64

55

67

s8

8o

V. P. Kukar’, I. N. Zhmurova, and R. I. Yurchenko, J. Gen. Chem. (U.S.S.R.), 1972, 42, 268. I. N. Zhmurova, R. I. Yurchenko, V. G . Yurchenko, A. A. Tukhar’, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 770. T. G. Edel’man and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1972,42, 1469. I. N. Zhmurova, R. I. Yurchenko, V. P. Kukhar’, L. A. Zolotareva, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1947. V. P. Kukhar’, I. N. Zhmurova, L. A. Zolotareva, and A. A. Tukhar’, Zhur. org. Khirn., 1972, 8, 756. V. V. Penkovskii, Yu. P. Egorov, and D. P. Khomenko, Dopovidi Akad. Nauk. Ukrain. R.S.R., Ser. By 1972, 34, 155 (Chem. Abs., 1972,76, 153 040). T. Kauffmann, G. Ruckelshauss, and D. Glindemann, Chem. Ber., 1973,106, 1618. W. E. Swartz, J. K. Ruff, and D. M. Hercules, J. Amer. Chem. SOC.,1972, 94, 5227. W. J. Stec, W. E. Morgan, J. R. Van Wazer, and W. G . Proctor, J. Inorg. Nuclear Chem., 1972,34, 1100. A. Schmidpeter, W. Zeiss, and H. Eckert, Z . Naturforsch., 1972, 27b, 769. H

214

0rganophosphorus Chemistry

R‘ I

Me,P.N=C-OAlk

+

N, R2-CH=CR3 -+

Me,<

H-C/

f-R1

+

AlkOH

\

R’ included Ph, and OEt

R’ included H, Me, and Ph R3included CN, C02Alk,COMe, COPh, and C0CH:CHPh Scheme 12

Scheme 13

completely to the right, unlike the situation in pyrrole where only the NHbonded form is present. Dipolar additions of the same type with the olehs, CH2= CH * C0,Alk may also result 61 in the formation of products containing the fused ring system (22).

Improvements and modifications of existing synthetic routes to the cyclic phosphazenes, such as N,P,Cl, (23) and its higher homologues, continue to appear with surprising frequency. These include a scheme 6 2 for the continuous preparation of cyclic homologues, (NPCl,)n, using a PC1,-C1,-NH,Cl mixture, where the unwanted linear polyphosphazenesare removed by aqueous extraction, leaving N,P,Cl, in 80 % yield. An earlier patent describes 6 3 how the yields of N,P,Cl, may be optimized by adding most of the phosphorus pentachloride to the ammonium chloride slowly and evenly over greater than 50% of the total reaction time. A similar objective64was achieved by treatment of the cyclic reaction products (NPCl,)n with aqueous sodium or

Ex

6a

W. Zeiss and A. Schmidpeter, Tetrahedron Letters, 1972, 4229. S. Beinfest, Z . Jacura, and P. Adams, U.S.P. 3 669 633 (Chem. Abs., 1972, 77, 75 802). J. E. Proctor, N. L. Paddock, and H. T. Searle, U.S.P. 3 667 922 (Chem. Abs., 1972,77, 75 752). H. Dreifus, U.S.P. 3 694 171 (Chern. Abs., 1973, 78, 45 818).

21 5

Phosphazenes

ammonium hydroxide, which selectively hydrolysed the higher oligomers. N3P3C16 can also be extracteds5 from the (NPCI,), mixture by heating the latter to a temperature of just greater than 140 “C in chlorobenzene, at which temperature the N3P3CIs and some NaPdCla volatilizes. The addition of magnesium chloride is reported 8s to be advantageous in the preparation of the lower cyclic homologues (NPC1z)3r from phosphorus pentachloride and ammonium chloride in chlorobenzene, and the cyclization of linear polychlorocyclophosphazenes has also been The only new methodsa for the synthesis of N3P3CIsreported this year comprises the gas-phase reaction of elemental phosphorus with sulphur and ammonia at 300-700 “C to give PN1-zSo.l-l, which is followed by reaction with chlorine at 500-800 “C:N3P3Clsis left as a condensate from the latter step. As previously noted, the reaction of amines with phosphines in the presence of carbon tetrachloridez6may be used to prepare novel cyclic phosphazenes

R

=

H, Me, Ph, CH,Ph, NMe,, OAlk, or SAlk) Scheme 14

in a simple, one-step, reaction (Scheme 14). The cyclic products were previously obtained by an independent route. The wide scope of the method is demonstrated by the fact that sulphur can also be incorporated into a phosphazene ring in a similar way (Scheme 15).

yNH +

Me

Me/ \ NH

PPh, ‘NH P6h,

CC14-NEtS

Me,

4N-?$hz S +:N C1Me’%-P6hz

Scheme 15

Full detailss9 of the preparation of the cyclophosphazenes (24) have been published. These compounds, which contain the P-H rather than an N-H bond, were obtained by the reaction shown in Scheme 16, as reported last year. OS

O9

J. K. Maund and C. H. G . Hands, U.S.P. 3 677 720 (Chem. Abs., 1973,78, 16 988). S. D. Radosavljevic and J. S. Sasic, Glas. Hem. Drus. Beograd., 1971, 36, 179 (Chem. Abs., 1972, 77, 159 647). H. Schadow, G. Trojna, and H. Scheler, 2.Chem., 1972, 12, 336. H. A. Lehmann, G. Sadowski, and G. Boden, Ger. (East) P. 91 016 (Chem. Abs., 1973, 78, 45 81 1). A. Schmidpeter,J. Ebeling, H. Stary, and C. Weingand, Z . anorg. Chem., 1972,394,171.

216

0rganophosphorus Chemistry

R1, RlzP=N-PR2,

I

NHP

II

NH

+ R3P(OPh)t

--+

N

,R2

q4 N\ N

‘fLR2

R1

+

2PhOH

‘6

H ’

‘R3

(Rl, R2and R3included, Me, Ph, and NMe,) Scheme 16

A new ring system (25) containing sulphur(1v) has been obtained 70 from the reaction of S(NSO), with phosphorus pentachloride [cf. compound (14) which is the sulphur(v~)analogue]. Other products from this reaction included

Scheme 17

‘O

H. W. Roesky, Angew. Chem. Internat. Edn., 1972, 11, 642.

21 7

Phosphazenes

N3P3C1, and CI,P=N-P(O)CI,. Sulphur has also been incorporated 71 into a phosphazene ring system in a more conventional style by way of the reactions shown in Scheme 17. The isomers (26) and (27) were readily distinguished by lH and 31Pn.m.r. spectroscopy.

5 Properties of Cyclic Phosphazenes Halogeno-derivatives.-A series of chloro- and bromo-derivatives of general formula N3P3F,X,-n (X = C1 or Br ;n = 2-4) has been prepared 7 2 by reaction of the dimethylamino-derivativesN3P3Fn(NMe2)6-n with hydrogen chloride or bromide. Some of the more volatile chlorofluoro-compounds could be obtained by reactions with hydrogen chloride in refluxing nitrobenzene at atmospheric pressure, but in most other cases reactions were carried out in sealed tubes. In reactions with hydrogen bromide it appeared more difficult to displace dimethylamino-groups at a =.P(NMe2)2centre than at a =PFNMe, centre, since the non-gerninal isomer (28) gave two of the three possible

(0'

Br

\

NMe,

isomers (29), (30), and (31), in each of which one dimethylamino-group was retained. In general, cis-trans isomer ratios changed during reactions with

,"

N

,P?- ->P, c1 I : + i I c1 MeW, - ,NMe B

MFs

~

- MC1,

72

F'

c1

(3 2)

f

B

/ \

c1

F\ p, /F ,P ,.--..,P F 1: ':I F MeNL- /NMe

(M = AsorSb)

\F (33)

M. Bermann and J. R. Van Wazer, Znorg. Chem., 1972, 11,2515. P. Clare, D. B. Sowerby, and B. Green, J.C.S. Dalton, 1972, 2374.

218

Organophosphorus Chemistry

hydrogen halides, presumably reflecting differences in thermodynamic and/or kinetic control. The fluorination of the inner salt (32) by antimony or arsenic trifluoride to together with details of its lH, llB, 19F,and 31P give (33) has been n.m.r. spectra. 31P N.m.r. spectroscopy showed 7 4 that the bis(isothiocyanato)-derivative N3P3C14(NCS)z,reported last year, contains the EP(NCS)~ grouping, and infrared spectroscopy indicated the presence of a P-N(exo) bond. The same cyclophosphazene structure is retained in its reaction products with alcohols, N3P3Cl4[NH(0R)Sl2 (R = Me or Et). Attempts 7 5 to effect the partial replacement of chlorine atoms in N4P4C18by isothiocyanato-groups resulted in the the formation of a mixture of products N4P,C18-n(NCS)n (n = 1-5), components of which were identified by mass spectrometry. Further details of the preparation and properties of the interesting fusedring compound (34) from phosphorus pentachloride and ammonium chloride

Ci

(35) (3 4)

have a~peared.’~ The n.m.r., mass, and infrared spectra of (34), and of its previously reported dimethylaminolysis product, were discussed and an appraisal made of its structure in terms of c- and n-bonding effects. The relationship between the localized and delocalized models of the n-electronic structures of the cyclophosphazenes has been established.7 7 It was pointed out that both approaches are not fundamentally different and must lead to the same conclusions if energy-optimizedparameters are used throughout. The e.s.r. spectrum of y-irradiated N3P,CI, shows78that the resultant anion has an unpaired electron confined entirely to a single phosphorus and two chlorine atoms. The structure of this anion at 77 K may thus be represented as (35). The 35Cln.q.r. spectra of N3P3CI6,N4P4C18,and several of their derivatives, whose crystal structures have been determined, reveal 7 5 that there is an approximately linear relationship between the 35Cln.q.r. frequency and P-C1 bond length. 7s 74 76 7e

H. Binder, Phosphorus, 1972, 1, 287. R. L. Dieck and T. Moeller, J. Znorg. Nuclear Chem., 1973, 35, 75. R. L. Dieck and T. Moeller, Inorg. Nuclear Chem. Letters, 1972, 8, 763. R. T. Oakley and N. L. Paddock, Canad. J. Chern., 1973,51, 520. G. Doggett, J.C.S. Faraday IZ, 1972, 68, 2075. S. P. Mishra and M. C. R. Symons, J.C.S. Chem. Cornm., 1973, 313.

219

Phosphazenes

No less than three independent studies 79-81 of the oriented single-crystal Raman spectra of N,P,C16 have been made. These are in generd agreement and a reasonably comprehensive assignment of the vibrational modes in this molecule is now possible. Similar work has been carried out 81 on N,P,Br, and, contrary to earlier suggestions, there is also some evidence81that this molecule has a non-planar ring in solution. Force constants have been calculateds2 for N3P3C16and N3P3Br6,but which may require slight revision in view of the new vibrational assignments given in the papers noted above. High-temperature thermodynamic data have been obtained for cyclic chloro- and bromo-cyclophosphazenes. Amino-derivatives.-The monoamino-derivativeN3P3F5NH2 readily eliminates hydrogen chloride on reaction s 4 with oxalyl chloride : 8oy

2 N,P,F,.N€-i,

4-(COCI),

-HC'+

N,P,F,-NH*CQ*CO*NH*N,P,F,

More results have been published which are relevant to an understanding of the factors which determine the mode of replacement of halogen atoms in homologues of the type (NPX2)3,4(X = hal) by ammonia and by amines. Thus the bromide N3P3Br6reacts with ammonia to give the geminal product (36), 8 6

(36) which has a similar structure to the analogous chloride, N,P,Cl,(NH,),. More details of the preparation of the adduct N,P,(NH,),,HCl from N,P,Cl6 and liquid ammonia have appeareds6 and it is also reported that the phospham obtained by heating this adduct has a good flame resistance. In a comprehensive study87of the reactions of N3P3C16with ethylamine, derivatives with the following degrees of chlorine atom replacement have been isolated : N,P3C16-,(NHEt), [n= 1, 2 (two isomers), 3, 4, and 61. Of those derivatives (n = 2, 3,4) where isomers are possible, only when n = 4 was a geminal isomer obtained, as shown by lH n.m.r., basicity measurements, and the preparation of derivatives of the type N,P,(NMe,),(NHEt),_,, starting from dimethylamino-derivatives, N,P,C16-n(NMe,)n, of known structure. A surprising 7s

81

85

D. M. Adams and W. S. Fernando, J.C.S. Dalton, 1972,2503. J. Klosowski and E. Steger, Spectrochim. Acta, 1972, 28A, 2189. J. A. Creighton and K. M. Thomas, Spectrochim. Acta, 1973, 29A, 1077. K. S. Addison, T. R. Manley, and D . A. Williams, Spectrochim. Acta, 1973, 29A, 821. G . M. Neumann, Thermochim. Acta, 1972, 4, 73. H. Thamm, T. P. Lin, 0. Glemser, and E. Niecke, 2. Naturforsch., 1972, 27b, 1431. R. L. Dieck and T. Moeller, J. Inorg. Nuclear Chem., 1973, 35, 737. E. Kobayashi, N@pon Kagaku Kaishi,1972, 38 (Chem. Abs., 1972, 76,94 023). R . N. Das, R. A. Shaw, B. C. Smith, and M. Woods, J.C.S. Dalton, 1973, 709.

220

Organophosphorus Chemistry

feature of this system is that the trisethylamino-derivative contains only monoaminolysed phosphorus atoms, i.e. EPClNHEt groups in a nongeminal structure, whereas the tetrakisethylamino-derivative contains a =PCl2 group. Emphasis has recently been placed on the role of the nucleophile in determining the course of these reactions and it was suggested in this paper that ethylamine, i-propylamine, and t-butylamine produce geminal products partly as a result of hydrogen-bonding effects, such as depicted in (37), which make the phosphorus atoms more electrophilic.

R3

The cis-trans isomer ratio in the non-geminal dimethylamino-derivatives N3P3C14(NMe2)2 is determined by kinetic effects when reactions are carried out in benzene, chloroform, or THF, but in acetonitrile the ratio approximates to that which obtains at equilibrium.88It was also calculated 89 that the transisomer, which generally predominates, is favoured as a result of a higher entropy of formation than the cis-isomer. The fact that the latter isomer is favoured on enthalphy grounds suggests it may have a non-planar ring to accommodate an expected steric interaction between the cis-dimethylaminogroups. It is worth noting, however, that there are little or no steric interactions between dimethylamino-groups in cis-N,P,Cl,(NMe,), in the solid state (see Section 7). The binding energies of the phosphorus (2s and 2p), nitrogen (Is), chlorine (2s and 2p), and fluorine (1s) core electrons have been measuredgoby ESCA methods on a series of dimethylamino- and fluorodimethylamino-derivatives of N,P3Cl,. The results allow a distinction to be made between the binding energies associated with both phosphorus and chlorine in =PCI, and cPClNMe, groups, as well as between endo- and exo-cyclic nitrogen atoms, but do not allow structural assignments to be made where isomers are possible. It was concluded that the phosphazene ring is able to redistribute charge differences accompanying changes in substituent electronegativity, and that the higher nitrogen (1s) binding energies of the dimethylamino-N atoms relative to those in the ring N3P3(NMe&may favour protonation at a ring nitrogen atom. A subsequent crystal structure has shown that this is the case (see Section 7). J . M. E. Goldschmidt and M. Segev, Inorg. Nuclear Cliem. Letters, 1973, 9, 161. J. M. E. Goldschmidt and M. Segev, Inorg. Nuclear Chem. Letters, 1973,9, 163. B. Green, D. C. Ridley, and P. M. A. Sherwood, J.C.S. Dalton, 1973, 1042.

221

Phosphazenes

Distannylamines undergo exothermic reactions with N3P3F6,'l and the products of these reactions subsequently react with pyrophosphoryl fluoride:

(R = MeorSnMe,)

Tri(stanny1)amines may be used to cyclize diphosphazenes in a similar manner to that accomplished with disilazanes: SO,(N=PCI,),

1- (Me3Sn),N --+

N , =PCI \

02S,

,N-SnMe, N=PCI?

The most detailed study, to date, of the reaction of N,P,Cl, with dimethylamine has appeared.g2When dimethylamine was added very slowly at - 78 "C to a solution of N,P,CI, in diethyl ether, non-geminal products, N,P4Cl,-n(NMe2)n (n = 2-6), were mainly obtained. The proportion of geminally substituted products was raised as the rate of dimethylamine addition was increased, so that the number of isomers finally obtained was n = 3 (two), n = 4(four),andn = 5(three).Structuralassignmentsweregenerally possible by lH n.m.r. and infrared spectroscopy. The latter results are dealt with in greater depth elsewhere,93in which isomers were best distinguished by examination of P-NMe, stretching modes in the region 640-740 cm-l. The condensation of N,P,Cl, with o-phenylenediamine and with its acetyl derivative in the presence of a tertiary base has enabled (38)94and (39)96to be

/I\

Cl

c1

COMe

(39)

(3 8) isolated. The diphenyl derivative (39) was considerably more thermally stable than the analogous diamino-derivati~e.~~ N3P,C16 and N,P,CI, react with thiourea or with ammonium thiocyanate to give thio-derivatives of the type (NP[SC(=NH)NH,],},,, which, in turn, give salts of metathiophosphinic acids, [NP(SH)2]3,4,with sodium hydroxide O3

@IL O4

@

H. W. Roesky and H. Wiezer, Chem. Ber., 1973,106,280. D. Millington and D. B. Sowerby, J.C.S. Dalton, 1972, 2035. D. Millington and D. B. Sowerby, Spectrochim. Acta, 1973, 29A, 765. G. F. Telegin, V. V. Kireev, and V. V. Korshak, Doklady Akad. Nauk S.S.S.R., 1972, 206, 1137. G. F. Telegin, V. V. Kireev, and V. V. Korshak, J. Gen. Chem. (U.S.S.R.),1972,42,1490.

222

Organophosphorus Chemistry

Amides may be converted into nitriles in excellent yield by reaction with N,P3C16.g7The initial steps in the reaction may be those shown in Scheme 18. The phosphoramidates formed are also known to dehydrate amides, so ensuring the complete breakdown of the phosphazene ring to a pyrophosphate.

Scheme 18

Alkoxy- and Aryloxy-derivatives-A scheme9 8 for the large-scale production of n-propoxycyclophosphazenes, mP(OPrn)2]n,from the (NPC12)nand propanol in pyridine has been proposed in which the solvent (chlorobenzene)and pyridine are recycled. Details99 of a process whereby flame-resistant properties are imparted on acetate fibres by a similer mixture of n-propoxycyclophosphazenes have been recorded in a patent application. The synthesis and thermal properties of benzyloxycyclophosphazenes, N3P,C16-n(OCH2Ph)n(n = 1-6), have been studied,loOand a series of pentakis(ary1oxy)monofluorocyclophosphazenes has been prepared lol by the route:

(R = H, Me, or OMe)

The 19Fand 31Pn.m.r. spectra of these derivatives were discussed in detail. Alkoxy- lo2and aryloxy- lo3 derivatives of the geminal bis(phosphazeny1)cyclophosphazene N,P,Cl,(N =PC1& have been prepared : N3P3CI,(N=PCI3),

*::

N3P,(OR),[N=P(OR),0H], (R = alkyl)

(R = aryl) B. Yanik and V. Zheshutko, J. Gen. Chem. (U.S.S.R.), 1972, 42, 260. J. C. Graham and D. H. Marr, Canad. J. Chem., 1972, 50, 3857. A.K.Z.O. N.V., Neth. Appl. 106 772 (Chem. Abs., 1972, 77,4870). B. Biehler, Ger. Offen. 2 056 613 (Chern. A h . , 1972,77, 103 237). loo M. Kajiwara and H. Saito, Kogyo Kagaku Zasshi, 1971,74,2583 (Chern. Abs., 1972,76, 141 321). l o l A. A. Volodin, V. V. Kireev, A. A. Fomin, M. G. Edelev, and V. V. Korshak, Doklady Akad. Nauk S.S.S.R., 1973, 209.98. O7

223

Phosphazenes

Both aryloxy- and alkoxy-derivatives were shown to contain a mixture of tautomers :

*

-N*(OR),OH

-NH-P(O)(OR),

and the alkoxy-derivatives underwent reactions with triphenylchlorosilane lo2 which were first order in the phosphazene but which occurred only at the exocyclic phosphazenyl groups : N,P,(oR>,[N=P(OR>20H]2

+ Ph,SiC1

+

N 3P3(0R), [N=P( 0R),OH] [N =P( 0R)(O Si Ph 3)OH]

+ RCI

The allylphenoxy-derivativesN,P,C~[OC,H,_,(cH,CH= CH,),J, (n = 1-3), which are of interest as plasticizers and flameproofing agents, have been obtained from the corresponding sodium phenoxides and N,P,CI,. lo4 The dehydration of amides to nitriles by N3P3Cl,has been noted in connection with amino-derivatives; nitriles may also be obtained in good yield from aldoximes and N,P,Cl, in the presence of triethylamine at ambient temperat u r e ~ It. ~is~possible ~ that the dehydration proceeds by way of a fast 1,4elimination of hydrogen chloride as in (40), since aldoximes of the type (41) were stable under similar conditions.

N3P3CI5* ON H

0

Alkyl and Aryl Derivatives.-N,P,F, reacts with methyl-lithium in diethyl ether solution to give the methylfluoro-derivativesN,P,F,-,Me, [n = 1, 2 (three isomers), 3 (2 isomers), 4, and 81, which were fully identified.lo6Other isomers were detected by g.l.c., but not further investigated. There was a preference for the formation of geminal isomers as shown in Scheme 19. The lH, 19F,and 31Pn.m.r. spectra of these derivatives were discussed in detail and the fluorine-atom replacement pattern described in terms of perturbation theory applied to a delocalized n-electron system. This predicts, for example, A. A. Volodin, V. V. Kireev, V. V. Korshak, E. A. Filippov, and V. M. Chukova, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1493. l o S A. A. Volodin, S. N. Zelentskii, V. V. Kireev, and V. V. Korshak, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1497. l o p H. Kawamura, K. Kotokuma, and S. Ikeno, Jap. P. 72 11 226 (Chem. A h . , 1972, 77, 61 560). l o 6 G. Rosini, G. Baccolini, and S. Cacchi, J. Org. Chem., 1973, 38, 1060. l o * T. N. Ranganthan, S. M. Todd, and N. L. Paddock, Inorg. Chem., 1973,12, 316.

lee

224

Organophosphorus Chemistry

Scheme 19* Me ,Me

F' F'

that the melectron density at the P-6 atom in (42) will be lower than that at P-4, so that further nucleophilicattack would be expected at P-6, as is observed. The octamethyl and decamethyl derivatives, N4P4Mesand N5P5MeI0,form complexes with molybdenum and tungsten hexacarbonyl of stoicheiometry (N,P,Me,)M(CO), and (N5P5Me10)M(C0),(M = Mo or W) in which metalnitrogen bonds are probably formed, although the stereochemistry about the metal atom was not unambiguously e~tab1ished.l~' Other complexesisolated in this study included {N4P4(NMe2)8} W(C0) and [N4P4Me9]+ [M(C0) 5T](M = Cr or Mo), the latter of which appears to have a donor-acceptor action between the ions because the C-0 vibrational modes indicate that the symmetry of the anion is lower than CqVand the lH n.m.r. signals are shifted upfield relative to those of N4P,Me,I. Attempts to prepare stannyl derivatives of cyclophosphazenes were unsuccessful.1oSN,P,Cl, and the lithio-derivative R,SnLi gave good yields of distannanes, R,Sn.SnR, (R = Bun or Ph), and other unidentified products, which may be formed via a lithio-chlorophosphazene, but there was no evidence for an entity containing an Sn-P bond. ESCA measurements on geminal N3P3F2Ph4and on geminal N3P3F3Ph3

* N, P, and F atoms are omitted; incoming methyl groups are indicated by spokes on the N,P, ring. l o ' N. L. Paddock, T. N. Ranganthan, and J. N. Wingfield, J.C.S. Dalton, 1972, 1578. l o 8 H. Prakash and H. H. Sisler, Inorg. Chern., 1972, 11, 2258.

Phosphazenes

225

show that the different types of phosphorus atom may be distinguished59by their 2p binding energies. 6 Polymeric Phosphazenes Interest in this topic is still growing and it has recently been the subject of a useful review. Potential applications of the polychlorophosphazenes have been surveyed logand their production by the controlled polymerization of N,P,Cl, and N4P4Cl,has been described.l1° (NPCl& has also been utilized ll1 in the synthesis of poly[bis(amino)phosphazenes], [NP(NHAlk),ln, and reaction of the same chloropolymer with diethylamine results in the nongeminal replacement of chlorine atoms to give [NPC1(NEt2)ln.The latter polymer was used as the precursor of a number of copolymers derived from primary amines, formulated as [NP(NEt,)(NHR)ln. Considerable effort has been made to explore the properties of potentially useful phosphazene polymers and copolymers with fluoroalkoxysubstituents,112-11eand polymers derived from the reaction of cyclophosphazenes with diols and biphenols have been reported.117-119Unusual polymers have been obtained by heating N,P,Cl,NH(CH,),Si(OEt),-n(OSiEt3)n (n = 1-3), whereupon triethylsilyl chloride is eliminated,lZo N,P3Cl, has been proposed to improve the properties of bitumin-based insulators,121carbon fibres derived from rayon,lZ2 and rotary moulded ny10n.l~~ Other derivatives of cyclophosphazenes are said to be useful in hydraulic fluids,lZ4making burn-resistant polymers, l Z 6and in increasing the wear resistance of a polysiloxane antifriction material.127 l Z 5 9

10 0

110 111 iia 113

114 116 116 117 118

118

120

181

122 iaa 194

126 128

127

B. Laszkiewicz and H. Struszczyk, Polimery, 1972, 17, 401 (Chem. Abs., 1973, 78, 17 144). K. A. Reynard and S. H. Rose, Ger. Offen. 2 220 800 (Chem. Abs., 1973,78,98 262). H. R. Allcock, W. J. Cook, and D. P. Mack, Znorg. Chem., 1972,11,2584. G. Allen and R. M. Mortier, Polymer, 1972, 13, 253. G. L. Hagnauer and N. S. Schneider, J. Polymer Sci., Part A-2, Polymer Phys., 1972, 10, 699. S. H. Rose and K. A. Reynard, U.S.P. 3 702 833 (Chem. Abs., 1973, 78,98 764). S. H. Rose and K. A. Reynard, S. African P. 71 07 092 (Chem. Abs., 1973,78,98 769). K. A. Reynard and S. H. Rose, U.S.P. 3 700 629 (Chem. Abs., 1973,78, 59542). R. Barclay and T. Sulzberg, High Polmer, 1972, 27, 589. M. Kajiwara and J. Saito, Nippon Kagaku Kaishi, 1972, 534 (Chem. Abs., 1972, 77, 20 063). K. Nakamara, Asahi Garasu Kenku Hokoku, 1972, 21, 75 (Chem. Abs., 1972, 76, 154 168). L. M. Volkova, V. V. Pisarenko, N. M. Voichenko, K. A. Andrianov, and M. I. Kabachnik, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1972, 51 8. Yu. V. Pokonova, D. A. Rozental, V. A. Proskuryakov, and E. A. Engberg, U.S.S.R.P. 358 343 (Chem. Abs., 1973, 78, 101 530). A. Fukiya and K. Matsuzawa, Jap. P. 72 29 939 (Chem. Abs., 1973,78, 98 901). M. Oba and M. Takamatsu, Jap. P. 72 23 190 (Chem. Abs., 1973,78,44 664). E. H. Kober, H. F. Lederle, and G. F. Ottmann, U.S.P. 3 627 841 (Chem. Abs., 1972, 77, 20 303). V. S. Frank and E. W. Lard, U.S.P. 3 641 193 (Chem. Abs., 1972, 76, 141 768). V. S. Frank, E. E. Stahly, and R. G. Rice, U.S.P. 3 676 311 (Chem. Abs., 1972, 77, 102 633). K. A. Andrianov, G. N. Bagrov, Yu. N. Vasil'ev, S. A. Kolesnikov, V. A. Fugol, A. V. Petrenko, V. M. Lebedev, A. P. Ovodkov, Ya. I. Mindlin, and L. M. Khananashvili, U.S.S.R.P. 328 159 (Chem. Abs., 1972, 77, 21 015).

2

N3P3C13(NMe2)3 (24s-4-cis-6)

Compound

165.2 (4) (P-NMe,)

162.3-165.8 (P-NMe,)

179.1 (4) (P-C) 199.4 (2) (P-CI)

158.5 (3)

167.5 (5) (N-1-P-2) 156.3 (5) (P-2-N-3) 159.7 (5) (N-3-P-4) 160.6 (4) (P-2-N-3) 156.5 (4) (N-3-P-4) 157.0 (4) (P-4-N-5)

Ring protonated in very 130 distorted ‘chair’ conformation; N-H = 86 (6) Pm

trans Phenyl groups; 131 P-P normal length of 220.8 (3) pm

108.1 (4) (at P-2) 103 .O (at P-4)

104.6 (2) (PP2C) 100.4 (1) (at P-4)

110.1 (4) (at P-2) 114.5 (4) (at P-4)

117.3 (2) (at P-2) 119.9 (2) (at P-4)

116.7 (4) 101.5 (8) Ring has very slight ‘boat’ 129 (in ring) (Me,NPNMe,) conformation; significant a-bond component in exo P-N bond

Averagea bond distanceslpm Averagea bond anglesldegrees Comments Ref. P-x LNPN LXPX P-N 157.9 (3) 161 . O (4) 118.2 (2) 105.0 (2) Ring has slight ‘chair’ 128 (P-NMe3 (in ring) (CIPNMe,) conformation. No steric 205.7 (2) interference between (P-CI) NMe, groups, which supply charge to C1 in a plane perpendicular to the ring

7 Molecular Structures of Phosphazenes Determined by X-Ray Diffraction Methods

.2

1 5

0

5

%

G 9

o\

t3 t3

155.6 (4)

NJ'ICI~(NM~ (2-cis-4-trans-6-trans-8) (P--co

162.6 (6) (P-NMea) 204.3 (3)

(P-m

159,162 (P-NMea 158, 152

(P-Q

178.3

12s

la*

-

119.3102.0122.3 (3) 103.5 (2)

-

120.4104.4121.8 (6) 106.2 (4)

121.3

F. R. Ahmed and D. R. Pollard, Acta Cryst., 1972, B28, 3530. S. J. Rettig and J. Trotter, Canad. J. Chem., 1973, 51, 1295. 110 H. R. Allcock, E. C. Bissell, and E. T. Shawl, J. Amer. Chem. Soc., 1972, 94, 8603. 1 8 1 H. Zoer and A. J. Wagner, Cryst. Structure Comm., 1972, 1, 17. l a * D. Millington, T. J. King, and D. B. Sowerby, J.C.S. Dalton, 1973, 396. 1 3 s G.J. Bullen and P. A. Tucker, J.C.S. Dalton, 1972, 2437. l a 4 H. P. Calhoun, N. L. Paddock, J. Trotter, and J. N. Wingfield, J.C.S. Chem. Comm., 1972, 875. l 1 5 G. J. Bullen and P. A. Tucker, J.C.S. Dalton, 1972, 1651. l a 8 W. Harrison and J. Trotter, J.C.S. Dalton, 1973, 61.

204.1 (P-CI) As preliminary report (Vol. 4)

157.0

155-164 (2) 175 (P-NMe,W)

155

NP4F4(NMe3, (2-cis-4-trans-6-trans-8)

136

P-N Ring has irregular 135 'crown' conformation

and one exocyclic N

cis Positions at W occu- 134 pied by one ring N

Ring has unusual 'crown- 133 saddle' conformation

Molecule has centre of 132 symmetry and ring has chair conformation

2

3 0

10 Photochemical, Radical, and Deoxygenation Reactions BY R. S. DAVIDSON

1 Photochemical Reactions The Norrish type I1 reaction of the phosphonate (1) is the first example of a P= 0 bond undergoing a photo-initiated hydrogen-abstraction reacti0n.l 0

II

(1)

OH

OH

CI,CP(OBui),

--%Cl,CP /

eMe,

/ ‘o?-rc/H,

0 Bui

I I

--+ CI,CP=O OBui

+ CH,=CMe2

Electron withdrawal by the trichloromethyl group is thought to have an activating influence upon the P=O bond by reducing the degree of p,-d, overlap. Irradiation of triaryl phosphates leads to reaction via cleavage of an aryl-oxygen bond and the products of the reaction include biaryls.2Crossover

RC,H,OPO,H,

+

MeCHO

Y. Ogata, Y. Izawa, and T. Ukigai, Buff. Chem. SOC.Japan, 1973, 43, 1009.

’ R. A. Finnegan and J. A. Matson, J. Amer. Chem. Soc., 1972,94,4780. 228

Photochemical, Radical, and Deoxygenation Reactions

229

experiments indicate that the reaction is intramolecular and all attempts to capture free aryl radicals and carbenium ions were unsuccessful. From the observation that electron-donating substituents in the aryl rings enhance the quantum yield of the reaction, it was postulated that a charge-transfer intermediate of the type (2) was involved. Irradiation of the phosphoramidate (3) in Ac

0

(PhO)2POR

+

I (PhO)2P=0 (3)

oxygenated alcoholic solutions leads to phosphorylation of the alcoh01.~Since the quantum yield for phosphorylation is much lower when oxygen is absent, it was proposed that oxygen acts as a hydride acceptor. The reactions can also be catalysed by base. Further details have now been given of the mechanism of photodecomposition of the phosphonium salt (4).4 The rate of product formation is increased

Ph + X

Ph3kH2C0,Et

1 1

*

+ Ph,PCH,CO,Et PhH,PhX,PhPh

PhCH,CO,Et

t /

(CH ,C02Et)

CH2C02Et

+ X'+

Ph3P

as the solvent is changed from protic to dipolar aprotic. Change of the counter ion from chloride to iodide also favours the reaction. These observations led to the proposal that reaction occurs from an incompletely dissociated ion pair and that excitation of the salt initiates electron transfer from the anion to the phosphonium cation, which subsequently undergoes homolysis. Exposure of solutions of lithium phosphides to oxygen causes a chemiluminescent r e a c t i ~ nSince . ~ the emission spectrum corresponds to the fluorescence spectrum of the phosphide, it was suggested that the oxidation reaction produces an excited species which energizes a ground-state phosphide molecule. 2 Phosphinidenes and Related Species Further evidence has been adduced in support of the premise that phenylphosphinidene is produced on thermolysis of pentaphenylcyclopentaphosS. Matsumoto, H. Masuda, K.4. Iwata, and 0. Mitsunobu, Tetrahedron Letters, 1973, 1733. Y . Nagao, K. Shima, and H. Sakurai, Bull. Chem. SOC.Japan, 1972,45, 3122. R. A. Strecker, J. L. Snead, and G. P. Sollott, J. Amer. Chern. SOC.,1973,95, 210.

230

0rganophosphoms Chemistry

I-

PhCrCPh

Ph

ph)+ph ,P-P

+

Ph

Ph

phMph

/ P, P ,P-Ph Ph 1 Ph

\

+

Ph

I

Ph

\

EtSClipCH=CHz

PhP.

\

CH,CH=CH2

+ PhPSEt

+

CH2=CHeH2

JEtSCH,CH=CH,

PhP(SEt)2

+ CH2=CHCH2

phine (5).6 Products formed by thermolysis of the phosphine in the presence of diphenylacetyleneappear to be derived from this intermediate. Decomposition of the phosphine in the presence of ally1 ethyl sulphide gives a product (6) via the phosphinidene apparently inserting into a C-S bond. However, this product may be produced by a purely radical process. Ph

II

0

Thermolysis of the phosphine oxide (7) appears, from trapping experiments, to involve the formation of phenylphosphinidene oxide. Rationalization of the formation of (8) required the free use of mechanistic gymnastics. 3 Radical Reactions The reactions of alkoxyl and thiyl radicals with tervalent phosphorus coma

A. Ecker and U. Schmidt, Chem. Ber., 1973,106,1453.

' J. K. Stille, J. L. Eichelberger, J. Higgins, and M. E. Freeburger, J. Amer. Chem. SOC., 1972,94,4761.

Photochemical, Radical, and Deoxygenation Reactions

231

pounds have been reviewed.8asb During the past year there have been extensive investigations of the structure and reactions of phosphoranyl radicals, in particular by the use of e.s.r. spectroscopy. The results of these investigations are now summarized. Structure.-The identification of a number of phosphoranyl radicals by e.s.r. spectroscopy has enabled the investigation of the energetics of several examples of pseudorotation. Thus in the case of (9a) there is an activation energy of 16-21 kJ mo1-1 for pseudorotation to (9b) with an energy difference between (9a) and (9b) of only 2.9 kJ mol-l. This is remarkable in view of the expected

I

NMe, (94

OBut (9b)

difference in apicophilicity between t-butoxy- and dimethylamino- group^.^ For the phosphoranyl radical (lo), produced by attack of a t-butoxyl radical OBut

H (10)

upon methylphosphine, there is a barrier of 22 kJ mol-l to pseudorotation.1° In the case of the phosphoranyl radicals (12a) and (12b), produced by attack of OBut

ButOP(OEt)2 + Me,”

t-butoxyl radicals upon the amino-phosphine (ll), it was not possible to examine the energetics of their interconversion owing to their susceptibility to A. G. Davies and B. P. Roberts, Accounts Chem. Res., 1972, 5, 387. D. G. Pobedimski, N. A. Mukmeneva, and P. A. Kirpichnikov, Russ. Chem. Rev., 1972, 41, 555. R. W. Dennis and B. P. Roberts, J. Organometallic Chem., 1973, 47, C8. P. J. Krusic, W. Mahler, and J. K. Kochi, J. Amer. Chem. SOC.,1972,94, 6033.

aa

ab

lo

232

Organophosphorus Chemistry

a-scission reactions.ll It appears that interconversion in the direction (12a)+ (12b) is the more favoured. The energy barriers to pseudorotation for radicals (9) and (10) contrast vividly with the very high value for pseudorotation of (13).la From the temperature dependence of the e.s.r. spectrum of (13) it

:. I

/

(J-O

appears that pseudorotation is occurring slowly on the e.s.r. timescale even at 120 "C, i.e. AG* > 54 kJ mol-l. This is an unprecedented barrier to pseudorotation between trigonal bipyramids of identical energies, i.e. topomers. A further surprising feature of this radical is its reluctance to undergo /3scission. The high energy barrier to B-scission was attributed to a build-up of strain in the intact five-membered ring as fragmentation of the other ring occurs. a-Cleavage Reactions.-A study of the comparative stability of the phosphorany1 radicals (14), (15), and (16) has been made.l39l4The order of stability Et

I -'-P< I

OR

(14)

OR

OR

OR

OR

(15 )

(16)

Et Et

was found to be (15) > (16)> (14). This order is in accord with the premise that a-scission occurs more readily from an apical than from an equatorial position. The greater length of apical bonds compared with equatorial bonds favours the a-scission process. Thus in the case of (14) no pseudorotation is necessary to bring an alkyl group into the required position for departure. In the case of (15), pseudorotation is necessary to bring an alkyl group into an apical position and this requires that alkoxy-groups be placed in equatorial positions. Since alkoxy-groups prefer to occupy apical positions, owing to the electronegativity of oxygen, there is a sizeable energy barrier to pseudorotation and consequently radical (15 ) is relatively stable. The process of pseudorotation for R. W. Dennis and B. P. Roberts, J. Organometallic Chem., 1972, 43, C2. D. Griller and B. P. Roberts, J. Organometallic Chem., 1972, 42, C47. l a A. G . Davies, R. W. Dennis, D. Griller, and B. P. Roberts, J. Organometallic Chem., 1972, 40, C33. l 4 A. G. Davies, D. Griller, and B. P. Roberts, J.C.S. Perkin 11, 1972, 2224.

l1

le

Photochemical, Radical, and Deoxygenation Reactions

233

radical (16) is not as unfavourable as that for (15) since it leads to a radical having an alkoxy and an alkyl group in apical positions. Hence radical (16) is less stable than radical (15). f3-Scission Reactions.-The ease of the B-scission reaction increases as the radical produced changes from primary to secondary, to tertiary, to ben~y1ic.l~ When very stable radicals, such as benzyl radicals, are produced, it probably makes little difference whether the benzyloxy-group occupies an apical or equatorial position. However, this is not likely to be the case for formation of less-stableradicals and it is proposed that p-scission occurs preferentially from equatorial p o ~ i t i o n s Thus . ~ ~ ~in~the ~ case where a phosphoranyl radical is produced by attack of a t-butoxyl radical and a &scission reaction ensues in which a t-butyl radical derived from the attacking butoxyl radical is produced, an intermediate pseudorotation step is required. The attacking t-butoxyl group will initially take up an apical position and therefore pseudorotation is necessary to bring it into an equatorial position for B-cleavage to occur. It has been previously reportedl6 that reaction of 13C-labelled radicals with tri-tbutoxyl phosphite produces a phosphate containing 75 % of the label. In this case pseudorotation must have taken place prior to the @-scissionreaction. However, in this particular case the barrier to pseudorotation will be small because identical groups are being exchanged. When a variety of ligands are present in the phosphoranyl radical, the ease of the p-scission reaction will be dependent upon the ease of placing the requisite alkoxy-group in an equatorial position. Thus the radical (15) does not readily undergo a p-scission reaction because this would require pseudorotation to a trigonal bipyramid having the alkyl groups, which are less apicophilic than alkoxy-groups, occupying apical positions. It is also argued that alkoxy-groups which contain a very bulky alkyl group will prefer to occupy apical positions. l4As a consequence,phosphoranyl radicals in which alkoxy-groups of widely differing size are present will undergo a @-scissionreaction to give a product in which the largest alkoxy-group is retained in the phosphorus-containingproduct. The ease with which phosphorany1 radicals undergo B-scission increases as the degree of substitution in the alkyl groups increases, e.g. the stability of the following radicals is in the order ButOP(OMe), > (ButO)P(OEt), > (ButO)P(OPri), > (ButO),P. ,8-Scission reactions of the radicals (17),14 (18),14and (19)9have been observed and in the case of (18) it was suggested that the ring probably occupies a diequatorial position.

I

0'

-"y*<

I'OEt EtO

l6

-+ CH2CH20P(OEt)2

II

0

G. B. Watts, D. Griller, and K. U. Ingold, J. Amer. Chem. Soc., 1972, 94, 8784. W. G. Bentrude and R. A. Wielesek, J. Amer. Chem. SOC.,1969, 91, 2406.

0rganophosphorus Chemistry

234

'\hL

OEt

* CH2CH,CH20P(OEt), II

0

Relative Ease of a- and p-Scission Reactions.-The rather odd situation, that a-scission reactions, e.g. displacement of amino-radicals from amino-phosphines by butoxyl radicals 11$l 7 and displacement of alkyl radicals from trialkylphosphines by t-butoxyl radicals, often occur in preference to the more thermodynamically favourable ,kission reactions, has been the subject of discussion. The thermodynamic favourability of the latter reactions are due to the formation of the relatively strong P=O bond (estimated as being between 500 and 600 kJ mol-l). It is now suggested that the major portion of this stabilizing energy may not be available in the transition state for B-scission.ls From a variety of calculations l8,l9on a number of a- and @-scissionreactions it has been concluded that, to a first approximation, the relative ease of B-scission to a-scission in a reaction initiated by attack of a radical R-A* upon a molecule XP(OEt)2is determined by the relative strengths of the R-A and P-X bonds. As we have seen previously,conformational effects are also of paramount importance in determining the relative ease of the two reactions. The rate of attack of t-butoxyl radicals upon a series of phosphonates XCGH,P(OMe),(X = p-MeO, p-C1, or rn-CF,) is independent of the nature of X.19 Other Aspects of the Chemistry of Phosphoranyl Radicals.-Phosphoranyl radicals have been trapped by olefins and the radicals so produced identified by e.s.r. spectroscopy.12In a number of cases it has been observed that the tervalent phosphorus compound produced in an a-scission reaction reacts with the radicals present in solution to give a phosphoranyl radical.l0* For example, formation of t-butyl dimethylphosphinite was observed in the reaction of t-butoxyl radicals with tetramethylbiphosphine. The phosphinite was found to react with the t-butoxyl radicals to give an identifiable phosphorany1 radical.lo Formation of phosphoranyl radicals by attack of alkyl radicals upon 11913

la

lD

J. R. Roberts and K. U. Ingold, J. Amer. Chem. SOC.,1973, 95, 3228. W. G. Bentrude, E. R. Hansen, W. A. Khan, T. B. Min, and P. E. Rogers, J. Amer. Chem. SOC.,1973,95,2286. W. G. Bentrude, J.-J. L. Fu, and P. E. Rogers, J. Amer. Chem. SOC.,1973,95, 3625.

Photochemical, Radical, and Deoxygenation Reactions

235

tervalent phosphorus compounds has been investigated further. Apparently the reaction of methyl radicals with trimethyl phosphite is rever~ible.~~ Reaction of phenyl radicals with phosphites has been shown to be a very rapid process, e.g. the rate constant for reaction with trimethyl phosphite at 60 "C is approximately 106-107 1mol-1 S - ~ . ~ OBoth kinetic 2o and product 21 studies have confirmed that the photolysis of phenylazotriphenylmethaneand iodobenzene in the presence of phosphites brings about reaction via the intermediacy of phenyl radicals. 31PCIDNP effects have been observedebs2 2 in the reaction of phosphites with t-butoxyl, phenyl, and halogen radicals. This has been taken as further evidence for the formation of phosphoranyl radicals in these reactions. Rate constants for the reaction of phosphites with t-butylperoxyl radicals have been evaluated.23 Reaction with triphenyl phosphite results in displacement of a phenoxyl radical. Chlorine radicals attack phosphorus trichloride to give a phosphoranyl radical, which reacts with oxygen to give a peroxyl radical. Further kinetic measurements have been made on the radical-initiated autoxidation of dialkyl phenylphosphonites.24 The rate was shown to be proportional to the concentration of the phosphorus ester and of the initiator (AIBN). The formation and properties of phosphorus-containing radicals, other than phosphoranyl radicals, have been reported. Dialkoxyphosphonyl radicals are produced by hydrogen abstraction from dialkyl phosphonates by t-butoxyl radicals.25 Another interesting method for the formation of radicals involves reaction of t-butoxyl radicals with tetraethyl pyrophosphite (20). A variety of phosphonyl radicals 26-z7 and related radicals 2 6 s 2 7 have been shown to react ButO'

+ (EtO),POP(OEt)Z

+ ButOP(OEt),

+ (Et0)2PO'

(ButO) ,P'(OE t)

+ CHz=CHC02H

P032t ao I1 z2

a3 84

p6

z8 s7

__f

H02CkHCH2P032-

J.-J. L. Fu, W. G. Bentrude, and C. E. Griffin, J. Amer. Chem. SOC.,1972, 94, 7717. J.-J. L. Fu, and W. G . Bentrude, J. Amer. Chem. SOC.,1972, 94, 7710. Y. A. Levin, A. V. Il'yasov, E. I. Gol'dfarb, and E. I. Vorkunova, Bull. Acad. Sci., U.S.S.R., 1972, 21, 1624. E. Furimsky and J. A. Howard, J . Amer. Chem. SOC.,1973,95, 369. Y. Ogata, M. Yamashita, and T. Ukai, Bull. Chem. SOC.Japan, 1972, 45, 2223. A. G. Davies, D. Griller, and B. P. Roberts, J. Amer. Chem. SOC., 1972, 94, 1782. A. L. J. Beckwith, Austral. J. Chem., 1972, 25, 1887. B. C. Gilbert, J. P. Larkin, R. 0. C. Norman, and P. M. Storey, J.C.S. Perkin IZ, 1972, 1508.

236

Organophosphorus Chemistry

HP03r

+ CHC0,H II

--+

-03PHCHC02H

I

'CHCOzH

CHC0,H

(23)

with olefins to give carbon radicals, e.g. (21),25 (22),26and (23).27In each case hindered rotation about the C-C bond in these radicals has been observed. This is attributed to there being a strong interaction between the half-filled radical orbital and the carbon-phosphorus o-bond, i.e. the stability is due to hyperconjugation. Phosphonyl radicals and related species are also adept at abstracting a halogen atom from carbon-halogen bond^.^^-^^ In the case of the reaction with benzyl bromide, the e.s.r. spectrum of the benzyl radical (24) was Reaction with oximes produced nitroxide radicals, e.g. (25). 2 7 (RO)2PO'

+ PhCH2Br

__f

(RO),PBr

+

II 0

+ PhCH2 (24)

+ CH~CH~CO~-

H P O ~ ~ T ICH~CH~CO~---+IPO~*-

HP027

+ MeCH=NOH

I

OH _t

MeCH-NOH

I

HP02-

T- MeCHNH-0'

I

HPOZ(25)

y-Irradiation of several phosphonium salts has been shown to produce radicals by loss of a hydrogen atom from the carbon atom attached to phosphorus.28In all cases there appeared, from the e.s.r. spectra, to be little conjugation between the radical and the phosphorus, i.e. very little dn-p,, bonding occurs in these compounds. Further details of the formation of dimeric cations by y-irradiation of trialkylphosphines have been given. 29

A. R. Lyons, G. W. Neilson, and M. C. R. Symons, J.C.S. Faraday 11, 1972,68, 807. A. R. Lyons and M. C. R. Symons, J.C.S. Faraday ZI, 1972,68, 1589.

Photochemical, Radical, atid Deoxygenation Reactions

237

y-Irradiation of tetramethylbiphosphine disulphide not only produces a radical anion, but also a radical formed by loss of a hydrogen atom from a methyl group. In this radical there is a strong interaction of the carbon radical with the phosphorus atom to which it is not attached, i.e. a hyperconjugative interaction between the P-P o-bond and the half-filled orbital occurs. The formation of alkanes by reaction of trialkyl phosphates with sodium in toluene is rationalized as involving the radical anion of the ester.30Reaction of the phosphorane (26) and the phosphinimine (27) with sodium was shown to Ph,P=NPh

-% Ph,P-RPh

(27)

xoj( 0

0 0 oxidation

NHBut

XO''NBut

I

0' (28)

lead to the production of radical anions:31 these were identified by e.s.r. spectroscopy. Electron attachment to hexachIorotriphosphazenewas shown to give a radical anion in which the unpaired electron is in an orbital with a high degree of s-character,3 2 i.e. little delocalization through the n-system occurs. Radical cations have been generated by electrolytic reduction of phosphonium compounds. 33 The nitroxide radical (28) was generated by oxidation of the corresponding amine.3 4 Similar radicals have been previously obtained in spin-trapping experiments. yH,Ar

I CH,Ar

3-

ArCH,

(29)

Rearrangement of (29) on heating has been shown to involve homolytic cleavage of the benzyl-phosphorus bond. 35 Crossover experiments demonstrated the intermolecularity of the reaction. a1 3 p 5s

a4 a6

H. Stetter and K. A. Lehmann, AnnuZen, 1973, 499. J. Kauffmann, G. Ruckelshauss, and D. Glindemann, Chem. Ber., 1973,106,1618. S. P. Mishra and M. C. R. Symons, J.C.S. Chem. Comm., 1973, 313. R. D. Rieke, R. A. Copenhafer.A. M. Aguiar, M. S. Chattha, and J. C. Williams, J.C.S. Chem. Comm., 1972, 1130. D. Gagnaire, A. Rassat, J. B. Robert, and P. Ruelle, Tetrahedron Letters, 1972, 4449. G. Mark1 and D. E. Fischer, Tetrahedron Letters, 1973, 223.

238

Organophosphorirs Chemistry

4 Deoxygenation Reactions Ozone and 0zonides.-The rate constants for reaction of ozone with triphenylphosphine and triphenyl phosphite at - 90 "C have been determined as being 3 k 1 x lo4 and 5 _+ 2 x lo31 mol-1 s-l, re~pectively.~~ The instability of, the triphenylphosphineozone adduct is not due to its ready decomposition to the phosphine and ozone. Reaction of the deuteriated olefins, MezC= C(CD,), and MeCD3C= CMeCD, with singlet oxygen, generated by reaction of sodium hypochloritewith hydrogen peroxide and by photosensitization,gives a slightly different ratio of non-deuteriated to deuteriated products than when the triphenyl phosphite-ozone adduct is used as the oxidizing species.3 7 This suggests that the reactive species in the reaction of the latter compound may not be singlet oxygen. A further, more definitive piece of work has shown that the mode of decomposition of phosphite-ozone adducts is determined by the . ~ ~the case of the triphenyl phosphite-ozone structure of the p h o ~ p h i t e In adduct, decomposition via the zwitterion (30) is proposed. This undergoes Of

0'

pseudorotation to give (31), in which the most electronegative groups occupy the apical positions. Little structural reorganization is required for (31) to decompose to give triphenyl phosphate. In the case of phosphites which have their oxygen atoms as part of rings, there is a constraint upon the pseudorotation process of the quinquecovalent adduct. As a consequence, this type of adduct has less tendency to decompose via a zwitterionic intermediate such as (3 1). Certainly, phosphite-ozone adducts are finding increasing use as reagents for bringing about singlet oxygenation reactions. A recent example is

(RO)3P0

38

+ PhCHO + CH,O

S. D. Razumovskii and G. D. Mendenhall, Cunad. J. Chem., 1973, 51, 1257. K. R. Kopecky, J. H. van de Sande, Cunad. J. Chem., 1972, 50,4034. L. M. Stephenson and D. E. McClure, J . Amer. Chem. SOC., 1973, 95, 3074.

Photochemical, Radical, and Deoxygenation Reactions

239

the two-step conversion of benzene monoxide to benzene t r i ~ x i d e The .~~ deoxygenation of styrene ozonide (32) by phosphites is suggested as occurring nia an oxyphosphorane (33).40 Molecular Oxygen.-The stable peroxide (35) has been isolated from reaction of the phosphorin (34) with molecular oxygen.41 Further examples have been Ph

I

OPh 0,

~

benzene

Ph

(34)

enumerated of the reaction of phosphoranes with molecular oxygen to give cyclo-olebs, e.g. for the preparation of cyclopropenes and macrocyclic polyenes.4 2 Hydroperoxides and Peroxides.-Reaction of the phosphite (36), a powerful

8 -1

Me,CO,H

+

a o ) - - O D M e ‘ 0 \ /

But

(3 6)

Me,COH

’

But

Ph

>C=CH, Me

+-

\

1

curnyl peroxide

PhOH

+

Me,CO

4

f:oTi,

Catalytic species

anti-oxidant, with 1-methyl-1-phenylethyl hydroperoxide has been investigated. Products are formed via ionic and free radical p a t h ~ a y s . ~The ~ a ionic character of the rate-determining step is indicated by the sensitivity of the reaction to solvent changes. To account for the observed k i n e t i c ~ , ~it~was b proposed that an unidentified catalytic species was formed between the C . H. Foster and G. A. Berchtold, J. Amer. Chem. SOC.,1972, 94, 7939. J. Carles and S . Fliszar, Canad. J. Chem., 1972, 50, 2552. 4 1 A. Hettche and K. Dimroth, Chem. Ber., 1973, 106, 1001. 4 8 H. J. Bestmann and H. Pfuller, Angew Chem. Internat. Edn., 1972, 11, 508. ‘Iaa K. J. Humphris and G . Scott, J.C.S. Perkin ZZ, 1973, 831. ‘Isb K. J. Humphris and G . Scott, J.C.S. Perkin ZI, 1973, 826. 8a

4o

240

Organophosphorus Chemistry

hydroperoxide and the phosphate formed in the reaction. This species catalyses decomposition of the hydroperoxide by an ionic mechanism to give phenol and acetone. The rate of oxidation of diphenylphosphine oxide by hydroperoxides in basic solution is controlled by the rate of nucleophilic attack of the peroxide anion upon the phosphine Deoxygenation of the peroxy-anhydride (37) by triphenylphosphine leads to a keten as well as an

(37)

\

(38)

Bu,C=C=O

+ +

COz Ph,PO

anhydride;46the intermediate (38) was not isolated. Photo-oxygenation of the benzoxepin (39) gave a peroxide which was deoxygenated to (40) on reaction with trimethyl p h ~ s p h i t e . ~ ~

\

0

hu Methylene Blue-0,

(MeO)J’+

‘

0

\.&-..

0

0-

Oxaziridines and 0xadiazoles.-Oxaziridines are deoxygenated to imines by reaction with trib~tylphosphine.~~ By examining the effects of substituents in the oxaziridine ring upon the kinetics of the reaction, the conclusion was reached that the phosphine initially attacks the oxygen atom of the ring. The lack of a marked solvent effect indicated very little charge separation in the transition state. 1,2,5-0xadiazolesare deoxygenated to give din it rile^,^^^ 49 e.g. R. Curci and F. Di Furia, Tetrahedron, 1972, 28, 3905. W. Adam and J. W. Diehl, J.C.S. Chem. Comm., 1972, 797. J. E. Baldwin and 0. W. Lever, J.C.S. Chem. Comm., 1973, 344. S. Tamagaki, K. Sakaki, and S. Oae, Bull. Chem. SOC.Japan, 1972, 45, 3179. A. J. Boulton and S . S. Mathur, J. Org. Chem., 1973, 38, 1054. S. M. Katzman and J. Moffat, J. Org. Chem., 1972, 37, 1842.

I4

45

4e 4’ 48

OD

241

Photochemical, Radical, and Deoxygenation Reactions

(41)

(41), on heating with p h o s p h i t e ~ .Reaction ~~ is thought to occur via nitrile monoxide. Sulphoxides.-Penicillin sulphoxides are cleanly deoxygenated to sulphides on heating with phosphorus tribr0mide.5~Reaction of triarylphosphines with thionyl chloride produces sulphuryl chloride.51 This product reacts further with the phosphine. From the stoicheiometry of the reaction, the mechanism involving intermediate (42) was preferred to the alternative mechanism, which

c1

Ar,P

/ + S=O \

--+

c1

+ Ar,P-S,

.1

c1

/cl

-/

+ Ar3P0 It c1 \o”cl

(42)

Al“3k1 socl

Ar,PO

(43)

.1 Ar3PCI23- SO

.1+ 1

SCI,

AhP

Ar3PC12 c S

* S + SO2

involves intermediate (43). Phenylphosphine dichloride reacts with dimethyl sulphoxide in methanolic solution to give methyl hydrogen phenylphosphonate.52In a closely related investigation it was reported that alkylphosphonothioic dichlorides react with dimethyl sulphoxide to give the anhydride (44). 53 Alkylphosphonic dichlorides were postulated as intermediates. A new S

Me

II I

RPCl2 DMSO_ R-P-0-S,

II

S

+’

d

s-s,+/ I I R-p-0

Me

CI

c1-

OH

OH

I

RP-0-A-R

II

0

DMSO

II

0

(44)

-

1

c1 RPC12

II

0

Me

Me CI-

+ Me,S=S

+I Me$

60

11

62

63

+

S

P. Claes, A. Vlietinch, H. Vanderhaughe, and S. Toppet, J.C.S. Perkin I , 1973, 932. E. H. Kustan, B. C. Smith, M. E. Sobeir, A. N. Swami, and M. Woods, J.C.S. Dalton, 1972, 1326. R. J. Brooks, and C. A. Bunton, J. Org. Chem., 1973,38, 1614. M. A. Ruveda, E. N. Zerba, and E. M. de Moutier Aldao, Tetrahedron, 1973,29, 585.

242

-

Organophosphorus Chemistry

(Md)d’_

s Ph’

O \ (45)

0

MeOH

S’

I

OH

Ph

synthesis of allylic alcohols, utilizing allylic sulphoxides (45) as starting materials, has as a key step the cleavage of an intermediate sulphenate ~ ester. This is formed by a [2,3]-sigmatropicshift of the s ~ l p h o x i d e5 .5 ~In~this way the natural product nuciferal (46) was synthesized.

Mono- and Poly-sulphides and Elemental Sulphur.-Desulphurization

of sulphides by their irradiation in the presence of trimethyl phosphite has been The success of the reaction is utilized in a synthesis of cyclophanes, e.g. (47).56

(4 7)

probably due to the fact that the sulphides are dibenzylic sulphides. Desulphurization of the disulphide (48), derived from penicillin, to the sulphide (49) has been accomplished by use of trimethyl pho~phite.~‘ The polysulphide (50), which is prepared by heating a-naphthylaminewith sulphur, was shown to be a trisulphide by its reaction with triethyl phosphite; desulphurization produced 64

65

66

67

D. A. Evans, G. C. Andrews, T. T. Fujimoto, and D. Wells, Tetrahedron Letters, 1973, 1385. D. A. Evans, G. C. Andrews, T. T. Fujimoto, and D. Wells, Tetrahedron Letters, 1973, 1389. V. Boekelheide, J. D. Reingold, and M. Tuttle, J.C.S. Chem. Comm., 1973, 406. R. D. Allan, D. H. R. Barton, M. Girijavallabhan, P. G. Sammes, and M. V. Taylor, J.C.S. Perkin I, 1973, 1182.

Photochemical, Radical, and Deoxygenation Reactions

243

PhCH,CONH H H S S R

Yf

0)---~xCOfH2CC13

PhCHzCONHvR

O

Nxc02cH

(49)

(-Jy)yJ-J NHR

NHR

/

NHR

NHR

J-+ J)s& -s

(EtO),P+

(51)

(50)

the disulphide (51).58 Diarylmethylene-triphenylphosphoranes react with sulphur to give thiobenzophenones and triphenylphosphine s ~ l p h i d e . ~ ~ Dialkylmethylene-triphenylphosphoranesreact in a different manner to give polysulphides. N-Oxides, Nitroso- and Nitro-Compounds.-Pyrazine N-oxides are deoxygenated to pyrazines on heating with phosphorus oxychloride.6o A comprehensive review of the rearrangement reactions of axylnitrenes contains references to many deoxygenation reactions involving nitroso- and nitrocompounds.61Further examples of the synthetic utility, e.g. in the synthesis of (52),62 and examples which illustrate the scope of these reactions have been Thus, deoxygenation of suitable nitro-compounds in the presence

(52)

6B O0

OZ

63

A. F. Cockerill, M. J. A. Gutteridge, D. M. Rackham, and C. W. Smith, Tetrahedron Letters, 1972, 3059. H. Tokunaga, K. Akiba, and N. Inamoto, Bull. Chem. SOC.Japan, 1972,45,506. S . Fujii and H. Kobatake, J. Org. Chem., 1972, 37, 2635. J. I. G. Cadogan, Accounts. Chem. Res., 1972, 5, 303. T. Kurihara, E. Okada, and M. Akagi, Yakugaku Zasshi, 1972,92, 1557 (Chem. A h . , 1973. 78, 58 335). F. R. Atherton and R. W. Lambert, J.C.S. Perkin I, 1973, 1079.

244

Organophosphorus Chemistry

of aliphatic amines leads to the formation of nitrene-type products, e.g. azepines (53). Not all the nitro-compounds investigated gave azepines : in R2R3N P(NR*R3)3 HNR*R3 ~

(53)

some cases, amines and hydrazines were obtained. Deoxygenation of nitrosocompounds in the presence of aromatic amines, e.g. NN-dimethylaniline,gave

I

NO

(54)

(55)

substituted dimethylanilines, e.g. (54) and (55).64 Both the azepines and dimethylanilines are postulated as being formed by an insertion reaction of a nitrene intermediate. The finding that pentafluoronitrosobenzene is deoxygenated by phosphites in the presence of olefins to give aziridines in a stereospecific manner is suggestive of the reaction occurring via a singlet nitrene intermediate.65However, as always with these reactions, it is possible that a zwitterionic compound such as (56) is an intermediate. The question as to

R. A. Abramovitch, S. R. Challand, and E. F. V. Scriven, J. Org. Chem., 1972,37,2705. R. A. Abramovitch and S. R. Challand, J.C.S. Chem. Cornrn., 1972, 1160.

Photochemical, Radical, and Deoxygenation Reactions

245

whether nitrenes are intermediates has been tackled in a rather novel way.66 Azides, suitably labelled with deuterium, have been decomposed in a mixture of a nitroso-compound, a phosphite, and solvent. It was arranged so that the azide and the nitroso-compound will give similar products if nitrenes are intermediates. If, indeed, both azide and nitroso-compound react to give a nitrene, then the deuterium label will be distributed in the products in exactly the same way as when the azide is decomposed in the absence of the nitrosocompound. If, however, the nitroso-compound reacts via a complex with the phosphite, the distribution pattern will be different. By this technique it was shown that o-nitrosobiphenyl reacts with phosphites in triethyl phosphate solution via a nitrene, whereas in decalin and chlorobenzene solution an intermediate analogous to (56) is involved. Another application of this technique was to show that aromatic nitro-compounds are deoxygenated via nitrosocompounds. Decomposition of azides in the presence of phosphites can lead to phos-

(63) 66

P. K. Brooke, R. B. Herbert, and F. G . Hollinian, Tetrahedron Letters, 1973, 761.

246

Organophosphorus Chemistry

phorimidates, e.g. (57).s7 Isomerization of the olefinic system by light leads to ring closure to give (58). The deoxygenation of aliphatic nitroso-compounds has attracted attention. The fact that the relative yields of the two isomers (60) and (61) is dependent on whether the precursor is the azide (59) or the nitroso-compound (62) has led to the suggestion that the nitroso-compound is deoxygenated via an intermediate such as (63).gs The greater susceptibility of the aryl group to migrate to the positive nitrogen accounts for the greater yield of the imine (60) in the RCH ,C=CHCO,Et

I NO,

(64)

R C HFC- CHCO BE t

+k

RCHzC=CH-C02Et

I N-0 -0/ \p/

1 -o/ \o-

(Et0)3P =-

‘P(OEt),

Et*’POEt OEt

-+

(EtO),PO

+

RCHZC--CHCO,Et

II II

Nf 0

1 RCH,CH-CHCO,Et \ / I?

deoxygenation reaction. 8-Nitro-olefins of the type (64) react with triethyl phosphite to give N-hydroxyaziridines (65) and the interesting covalent compounds (66) and (67)6g.

S. A. Foster, L1. J. Leyshon, and D. G. Saunders, J.C.S. Cliern. Comm.,1973, 29. R. A. Abramovitch, J. Court, and E. P. Kyba, Tetrahedrort Letters, 1972, 4059. C . Shin, Y. Yonezawa, and J. Yoshimura, Tetrahedron Letters, 1972, 3995.

1I Physical Methods BY J. C. TEBBY

The abbreviations PIII, PIV, and P V 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 31PChemical shifts (BP) are upfield from 85 % phosphoric acid. Chemical Shifts and Shielding Effects.-Phosphorus-3 1. The application of lP n.m.r. to organophosphorus chemistry has been reviewed. The 31Pchemical shifts of primary, secondary, and tertiary phosphines, protonated tertiary phosphines, quaternary phosphonium salts, and phosphine oxides can be predicted using the empirical formula: BP = Bparent + m/?+ ny. Table 1 gives the chemical shift of the ‘all methyl’ parent, dparent, and the constants /3 and y , which have specific values for each type of compound: m is the number of /3 carbon atoms and n the number of y carbon atoms. The presence of p carbon atoms and their appropriate hydrogen atoms produce deshielding of the

P

RPH~ +163.5 -35.5

Y

+7

Type Sparent

Table 1 R~PH R ~ P +62 +99 -22 -13.5 +4 +10

R,~H +3.2 -8.6 +3

R,; -25.3 -3.7 +1.5

&PO -36.2 -4.0

+1

phosphorus nucleus, while y carbon groups cause shielding. The y shielding effect is attributed to the operation of a steric influence apart from bond angles and is probably associated with conformational changes. The high-field shift

E. Fluck, Chem.-Ztg., 1972, 96, 517. I*

247

248

Organophosphorus Chemistry

observed for cyclic compounds, e.g. 6~ = 53.7p.p.m. for (1) compared with 39 (calc.) for (2)and 34 p.p.m. for (3), is attributed to differences in conformation populations.2 Further examples have been published of the use of 31Pn.m.r. spectroscopy to study conformational and binding properties of biologically important phosphorus compounds3 such as nucleotides.* 8p of PI1 compounds. Large negative shifts, SP = -225, -222, and -264 p.p.m., have been used as evidence for the formation of the two-co-ordinate compounds (4),5(5),6 and (6).'

n

MeN+-;;NM e P

PF,(4)

(6)

SP ofP1I1 compounds. A comparison of Gp(obs.) and Gp(calc.), using a formula similar to that above, has been used to study cyclization effects upon the chemical shifts of tertiary phosphines. The observed shifts for phosphines with an unsubstituted five-membered ring were only slightly downfield of those calculated. Although one B-methyl group gave the expected increase in shieldMe

Me

Q I

Me

ing for both cis- and trans-isomers, two methyl groups as in (7) caused exceptionally large shielding, probably owing to large conformational changes.8 The introduction of unsaturation (conjugated to phosphorus) in the fivemembered ring causes deshielding of the phosphorus (see Table 2). In the phospholes, one P-methyl group produces slight deshielding but two p-methyl groups produce a marked shielding, as noted for the saturated compounds.@ L. D. Quin and J. J. Breen, Org. Magn. Resonance, 1973, 5, 17. D. G . Davis and G . Inesi, Biochim. Biophys. Acta, 1972, 282, 180; W. H. Huestis and M. A. Raftery, Biochem. Biophys. Res. Comm., 1972,49,428; D . G . Davis, ibid., p. 1492; R. H. Sarma and R. J. Mynott, Org. Magn. Resonance, 1972,4, 577. R. H. Sarma, R. J. Mynott, D. J. Wood, and F. E. Hruska, J.C.S. Chem. Comm., 1973, 140; R. H. Sarma and R. J. Mynott, J. Amer. Chem. SOC.,1973,95, 1641. A. F. Vasil'ev, L. V. Vilkov, N. P. Ignatova, N. N. Mel'nikov, V. V. Negrebeckij, N. I. Svecov-Silovskij, and L. S. Chajkin, J. prakt. Chem., 1972, 314, 806. a B. E. Maryanoff and R. 0. Hutchins, J. Org. Chem., 1972,37, 3475. ' S. Fleming, M. K. Lupton, and K. Jekot, Inorg. Chem., 1972, 11, 2534. J. J. Breen, J. F. Engel, D. K. Myers, and L. D. Quin, Phosphorus, 1972,2, 55. * L. D. Quin, S. G . Borleske, and J. F. Engel, J. Org. Chem., 1973,38, 1858.

Physical Methods

249 Table 2

I

CHIPh

6p

+14.4

I

CH2Ph

-7.9

0

The BP of the 3-phospholen (8; R = CH2Ph)is 23.5 p.p.m., which can be largely accounted for if it is assumed that the ring is equivalent to two ally1 groups, each of which would have an additional shielding effect of 4 p.p.m. compared with that of an ethyl group. The effect of a- and p-methyl substitution was studied for the derivatives (8; R = Me, CH2Ph, Ph, or Br).* Note that in

0 P

(PhCZC) ,P

acyclic systems the ethyl and vinyl groups appear to have a similar influence on d ~ The . phenylethynyl group, like CN, has a marked shielding effect when bound to phosphorus: dp increases almost linearly by 28 p.p.m. as each phenyl group of triphenylphosphine is replaced, the series finishing with B P = 88 p.p.m. for (9).l0A study of the dp values of 2-phospha-1,3-diazacyclohexanes has shown that the phosphorus atom is shielded most when the nitrogen atoms are orientated with their lone pairs of electrons axial; thus (IO), (ll), and (12; R = Et) have BP values of - 108.8, -94.3, and -86.8

p.p.m., respectively. The shielding is attributed to dn-pn bonding. The introduction of 5,5'-dimethyl substituents in (12) shields the P nucleus by 9-10 p.p.m. Although this could be attributed to the constraint of the N-methyl groups to equatorial sites with subsequent increase in the d,,-pn bonding, this was not confirmed by the geminal H-H coupling constants of the C-4 and C-6 10

L. I. Chekunina, A. I. Bokanov, and B. I. Stepanov, J. Cen. Chem. (U.S.S.R.), 1972,42, 985.

250

Organophosphorus Chemistry

methylene groups. l1 In the compounds R3P, R,PSR, RP(SR),, and P(SR),, successive replacement of R by SR deshields the phosphorus nucleus, e.g. S p = + 20, - 37, - 83.5, and - 115.5 p.p.m., respectively, for the ethyl derivatives. Replacement of SEt by SPh deshields the P nucleus further, which supports the hypothesis that deshielding is due to donation of the phosphorus lone pair of electrons to the d-orbitals of sulphur.12The change in 6r from Et,P to P(SEt), or P(SPh), is not far from linearity, which is similar to the Ph3P to (9) series discussed above but is in contrast to most other series, e.g. Et3Pto P(OEt),, or Me3Pto PF,. When the groups being exchanged have large differences in electronegativities, the intermediate compounds possessing both groups are strongly deshielded relative to that estimated by a linear change. This deshielding effect is therefore associated with a change in electron distribution in the o-bonds. The shielding constants for PCI, and the ethylchloroThe trifluorophosphines (13; Y = C1, Et,N, or Et) have been ca1c~lated.l~ methyl group normally has a deshielding effect compared with methyl, e.g. SP = 2.6,49.3, and 126.2for the tri-, di-, and mono-trifluoromethylphosphinesl4 compared with 62, 99.5, and 163.5 p.p.m. for the corresponding methylphosphines. In contrast, the fluorinated cyclic biphosphine (14) has BP = +90.5 p.p.m.15 Et

b--Y

/ c1

,CF,\ F&-P \cF/p-CF3

(1 3)

(14)

8~ of PIv compounds. A variation of 61, in a series of tetrahalides (15; X = Hal), taking the tetramethyl derivative (1 5 ;X = Me) as zero, bore a closer resemblance to the variation of 6,,c in CX4than of d,,,, in Six4, the deviation of 6si increasing with the electronegativity of X.16 The correlation between dp and the Taft CT* constants for non-conjugated diethyl phosphonates (16) is

0

0

II RP(OEt), (16)

Y

II PCH &HO (17)

0

II

Y,PCH=CHOH (18)

improved if one takes into account the number of a-CH bonds. For conjugated phosphonates in which the cz atom is sp2 carbon or is an atom bearing a lone pair of electrons, there is a possibility ofp,-d, bonding, which has been l1

l*

18

l4

l6

R. 0. Hutchins, B. E. Maryanoff, J. P. Albrand, A. Cogiie, D. Gagnaire, and J. B. Robert, J. Amer. Chem. SOC.,1972,94, 9151. A. I. Razumov, E. A. Krasil’nikova, T. V. Zykova, N. I. Sinitsyna, R. A. Salakhutdinov, and N. N. Bankovskaya, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1245. L. N. Krut-skii, T. V. Zykova, R. A. Salakhutdinov, and V. S. Tsivunin, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1484. R. Demuth and J. Grobe, J. Fluorine Chem., 1972, 2, 263. D. K. Kang and A. B. Burg, J.C.S. Chem. Comm., 1972, 763. H. C. Marsmann and H. G. Horn, Chem.-Zrg., 1972,96,456.

Physical Methods

25 1

estimated by subtracting the 8p calculated from o* from that observed (see Table 3). The results are used as evidence that a rise in d,-p, bonding in PxV

R dp(obs.) = dp(ca1c.)

Table 3 sp= spa sp C=CC=OCrC N 1-1216-18 26 13-19

0 10-17

F 7

c1

S

-7-

-9

0

compounds causes shielding of the P nucleus and that sulphur can act as an electron accept0r.l' Replacement of the ethyl groups in (17;Y = Et) by alkoxygroups decreases the concentration of the enol (18). This is attributed to an increase in d,-p, bonding by the alkoxy-groups, as reflected by the increased shielding of the phosphorus nucleus.18 The deshielding of the P atom in a series of cyclic salts and ylides (19) in comparison with their acyclic analogues (20) decreases as the possibility of dn-pn back-bonding by the substituents on phosphorus increases, i.e. as R 1= Me is replaced by R' = Ph or

R1= PhCOFH. If shielding is due to dn-pn back-bonding the biphenylene group is either increasing back-bonding by the other groups or it does not d,-p, bond efficiently it~e1f.l~ Note that 8p is -25 p.p.m. for (19; R1 = Ph, R2 = Me) and -21.5 for (20; R1 = Ph, R 2 = Me) and not as stated in the paper.lg A wide variety of phosphoryl enol ethers (21) have been compared with the corresponding methyl derivatives Y,P(O)Me. The pronounced shielding of phosphorus observed for the enol ethers was attributed to d,-p, bonding. The shielding is greatest when the double bond also bears a halogen ph,

0

II

Y tPCH=CH

,RH

QCR

2

RC 'hP" (23)

R' (24)

V. E. Bel'skii, L. A. Kudryavtseva, and B. E. Ivanov, J. Gen. Chem. (U.S.S.R.),1972, 42, 2421. l 8 A. I. Razumov, M. P. Sokolov, T. V. Zykova, B. I. Liorber, G . A. Savicheva, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.),1972, 42, 43. l B I. F. Wilson and J. C. Tebby, J.C.S. Perkin I, 1972, 271 3. l7

I*

*

252

Organophosphorus Chemistry

atom.20The upfield shift of d~ values for a series of vinyl compounds (22; Y = Et, Ph, Me2N, RO, or ArO) corresponded with an increase in the P=O stretching frequency.21The effect of having the double bond endo or exo has been studied for the diphosphonia-heterocycles (23) and (24). The exoderivatives (24) were considerably less shielded than the corresponding endocompounds. 2 2 Pyridyl substituents deshield phosphorus relative to phenyl, especially when the phosphorus atom is attached to the c1 position, e.g. BP = -8.2 for (25; R = a-pyridyl) but - 16.7 for (25; R = ~ h e n y l ) Although .~~ 0

Il'

(Eto) Pk (25)

(26)

there is little change in 8p with chain length of R on the series of half esters (26; R = ethyl to n-decyl), a y shielding effect was discernible for the isopropyl ester.24The sensitivity of SP to long-range structural changes makes it possible to analyse mixtures of polyphosphates quantitatively. 2 5 6~ of PV compoimds. The penta-alkylphosphorane (27) has 6~ = +90 p.p.m.26 This is in the same region as other phosphoranes which have five similar substituents, e.g. SP = 80 for PF5.Chemical shifts of dioxyphosphoranes have been reported in the range 39-47 p.p.m. The inclusion of the phosphorus atom as part of two small rings as in (28) reduces SP to + 17 p.p.m.,27 but a quite exceptional decrease is reported for another bicyclic compound

+

22

es

p5 96

T. V. Zykova, V. V. Moskva, A . I. Razumov, G . F. Nazvanova, and R. A . Salakhutdinov, J . Gen. Chem. (U.S.S.R.), 1972,42,1907; A. V. Dogadina, B. I. Ionin, and A. A. Petrov, ibid., p. 1914. A. N. Pudovik, L. A. Strabovskaya, G . I. Evstaf'ev, A. B. Remizov, and R. D . Gareew, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1847. M. S. Chattha and A. M. Aguiar, J. Org. Chem., 1973, 38, 1611. D. Redmore, J . Org. Chem., 1973, 38, 1306. A. A. Abduvakhabov, F. Kamaev, V. B. Leont'ev, K. Inoyatova, A. S . Sadykov, N. N. Godovikov, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R., 1971, 20, 2674. J. G. Colson and D. H. Marr, Analyt. Chem., 1973,45, 370. E. W. Turnblom and T. J. Katz, J. Amer. Chem. SOC.,1971, 93, 4065. E. Duff, S. Trippett, and P. J, Whittle, J.C.S. Perkin f. 1973. 972.

Physical Methods

253

(29): SP = -27 p.p.m.28Another rather low chemical shift (SP = + 2 p.p.m.) has been observed for bicyclic tetraoxyphosphorane (30).29 Replacement of alkoxy-groups by phenoxy had the usual shielding effect on the phosphorus nucleus of oxyphosphorane~.~~

(30)

Isotope eflects on 8 ~Substitution . of all the hydrogens of phenylphosphine by deuterium, which has less electrostatic deformation than H, moved SY upfield: SP is 122.3 for (31) and + 125.2 for (31 ;H = D).31Whereas monodeuteriation increased the SP of (32; n = 2) by 1.2 p.p.m., dideuteriation of (32; n = 1) to give CF3PD2increased SP by 2.9 p.p.m.14 Curbon-13. The 13Catom of the N-methyl group MeAin the aminophosphines The (33; X = C1 or OMe) is upfield of MeB, as is observed for the

+

Me* I

N P’ ‘Me”

Ph’

‘X (33)

9 c;”

4 4

directly bonded phenyl carbon atom in P-phenylphosphole (34) resonates ca. 10 p.p.m. downfield of the corresponding atoms in the phospholen (35) and divinylphenylphosphine. This may be the result of delocalization in the phosphole ring.33Calculations on the electronic structure of phosphole and pyrrole indicate that the electron density on the phosphorus atom of phosphole is considerably less than the electron density on the nitrogen atom of pyrr01e.~~ The effect of the phosphorus oxidation state on SC of four-membered heterocycles (36) has been examined. Conversion of a PII1compound to its salt or oxide shifts the C-2(4) resonance further downfield than in analogous acyclic compounds, but the P-Me 13Cresonance is deshielded less. The effect of the cyclic nature of the compounds could be to place more charge on the exocyclic In *O

ao 31

Is

aa

C. D. Hall, J. D. Bramblett, and F. F. S. Lin, J. Amer. Chem. Soc., 1972, 94, 9264. B. A. Arbuzov, Yu. M. Mareev, V. S. Vinogradova, and Yu. Yu. Samitov, Proc. Acad. Sci. (U.S.S.R.), 1972, 203, 618. D. B. Denney and F. A. Wagner, Phosphorus, 1973,2,281; F. Ramirez, K. Tasaka, and R. Hershberg, ibid., p. 41 ;F. Ramirez and H. J. Kugler, ibid., p. 203. S. J. Seymour and J. Jonas, J. Magn. Resonance, 1972, 8, 376. M. P. Simonnin, R. M. Lequan, and F. W. Wehrli, J.C.S. Chem. Comm., 1972, 1204. T. Bundgaard and H. J. Jakobsen, Tetrahedron Letters, 1972, 3353. H. L. Hase, A. Schweig, H. Hahn, and J. Radloff, Tetrahedron, 1973, 29,469.

254

0rganophosphorus Chemistry

P-Me than on its acyclic counterpart.36Fourier transform carbon-1 3 n.m.r. was used to show that the tautomeric equilibrium of D-fructose phosphate favours the P-furanose form.36

Hydrogen-1. A review of the use of lH n.m.r. spectroscopy for studying organophosphorus compounds includes a section on the chemical shifts of common phosphorus groups.37 The resonances of the phenyl protons in the potassium phosphides (37; R = H or Ph) and the corresponding amides -

PhRN K+ and carbanions PhRCH K+ showed that the two-co-ordinate phosphorus atom is a strong electron donor to the phenyl ring(s). The rnaximum shift of BH is for the para-protons and therefore the para-position accepts most negative charge, as is also the case for the amides and carbanions. However, the shift is greater for the latter compounds, the electron-donor _

_

_

properties to the ortho- and para-positions increasing in the order P < N < C. With regard to their donor properties to the meta-position, the increase is in -

-

-

the order N < P < C . 3 8 The spectra of ten phospholes indicate a definite deshielding of the ring protons compared with 2-phospholens, in accordance with the operation of a ring c ~ r r e n tThe . ~ deshielding effect of the phosphoryl group was used to establish the configuration of (38),39 and the pronounced deshielding of the ethyl protons of diethylamino-derivatives of (PNCI,), after three amino-groups have been introduced was used as evidence for the nongeminal assignments for the mono-, di-, and tri-substituted phosphazenes. 40 The anions of quaternary phosphonium salts have been used as shift reagents, Upfield shifts of up to 3 p.p.m. were produced by the aromatic ring currents of the tetraphenylborane anion. *l Studies of Equilibria, Reactions, and Solvent Effects.-The intermolecular association of biphosphines (39) was studied by n.m.r. Although only one methyl resonance was observed for a mixture of tetramethyl- and tetraphenylbiphosphines, lH-(P} double resonance showed that the resonance was associated with two different compounds with BP of 59 and 16 p.p.m., the new compound being (39; R1= Me, R2= Ph).42Evidence has also been presented ss

s7

40

41

G. A. Gray and S. E. Cremer, J. Org. Chem., 1972, 37, 3470. T. A. W. Koerner, L. W. Cary, N. S. Bhacca, and E. A. Younathan, Biochem. Biophys. Res. Conim., 1973, 51, 543. B. I. Ionin and T. N. Timofeeva, Russ. Chem. Rev., 1972, 41, 390. E. N. Tsvetkov, I. G. Malakhova, P. V. Petrovskii, E. I. Fedin, and M.I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 265. Y . Kashman and E. Benary, Tetrahedron, 1972, 28, 4091. R. N. Das, R. A. Shaw, B. C. Smith, and M. Woods, J.C.S. Dalton, 1973, 709. G. P. Schiemenz, J. Magn. Resonance, 1972, 6 , 2 9 1 . H. C. E. McFarlane and W. McFarlane, J.C.S. Chem. Comm.,1972, 1 189.

Physical Methods

255

for the existence of 1,2-diphenyldiphosphine in equilibrium with phenylyhosphine and pentaphenylcyclopentaphosphine.43The proton-decoupled 31P resonance of 1-methylphosphorinan split into two signals with different intensities when the sample was cooled to -80 "C. The splitting is attributed to slow interconversion of axial and equatorial conformers (40) and (41). Ph

Ph\ ,p-p\

/

R

R

(39)

A comparison with the spectra of a t-butyl derivative indicated that the conformer with an equatorial methyl (41) predominated by 2 : 1. However, this is a much lower preference than occurs in N-methylpiperidineand methylcyclohexane(95 % and 99 % equatorial methyl, respectively). The proportion of (41) decreased linearly as the temperature was raised and extrapolation indicated that the axial conformer (40) predominates at 25 0C.4431Pn.m.r. has also been used to study ester exchange in the phosphite (42),45halogen exchange in (43) 4 6 and (44),47and phosphite-spirophosphorane tautomerism (45) s (46).48 0

BuO,

I'-OPh

B L d (43,

(45)

II

MePX,

MePX,

(43)

(44)

(47)

Use of either S(+)- or R( -)-(47) as a chiral solvent for a mixture of meso and racemic modifications of (48) causes an extra splitting of the higher-field methyl resonance, which is attributed to the racemic modification. S( -)-aPhenylethylamine was not successful, which was attributed to the loss of hydrogen-bonding to the phosphoryl Solvent shifts on the methyl resonance were large for the para- and meta-tolyl esters but not the ortho43

44

47

b0

J. P. Albrand and D. Gagnaire, J. Amer. Chem. SOC.,1972, 94, 8630. S. 1. Featherman and L. D. Quin, J. Amer. Chem. SOC.,1973, 95, 1699. V. P. Evdakov, V. P. Beketov, and V. I. Svergun, J. Gen. Chem. (U.S.S.R.), 1973,43,51. K. Moedritzer, Phosphorus, 1973, 2, 179. J. G. Riess and R. Bender, Bull. SOC.chim. France, 1972, 3700. D. Bernard, C. Laurenco, and R. Burgada, J. Organometallic Chem., 1973, 47, 113. M. D. Joesten, H. E. Smith, and V. A. Vix, J.C.S. Chem. Comm., 1973, 18.

0rganophosphovus Chemistry

256

esters of (49).60The shifts induced by aromatic solvents (SIAS) was used in the conformational analysis of (50).51

0

0

II

II I

Pri- P- O -P-Pri

I

NMe2

Me,N (48)

(49)

Pseudorotation-The various attempts to rationalize the 'pseudorotation' process have been critically discussed. Six basic modes of rearrangement for a trigonal-bipyramidal molecule have been described. Examples of the six types of exchange are given in Scheme 1. The exchange M, produces no change, MI

M1,

% Scheme 1

is Berry pseudorotation or turnstile rotation, M, exchanges one apical and one radial group, M, exchanges either the apical groups or two radial groups (shown), M4 is aee, and M 5is the exchange of the two apical groups for two separate radial groups. The experimental evidence pertinent to distinguishing among these modes is analy~ed.~, The variable-temperature n.m.r. spectra of the alkylphosphorane (27) showed broadening of the methyl doublet below - 158 "C. The barrier to pseudorotation was estimated to be ca. 20 kJ r n 0 1 - l . ~ ~ The methyl resonance in the lH spectra of the fluoromethylphosphorane (51) remained a singlet when the sample was cooled to -70 "C but the fluorine doublet separated to two doublets corresponding to radial and apical fluorines, in accordance with the structure A double triplet was observed in the 31Pn.m.r. spectrum of (52) at 32 "C using Teflon n.m.r. cells. The signals broadened when the temperature was raised and became a quartet above 125 "C (Ea z 80 kJ mol-l). However, the spectra obtained using 10

61

sa 68

b4

R. A. Shaw and M. Woods, Phosphorus, 1972,2, 61. Yu. Yu. Samitov, R. D. Gareev, L. A. Stabrovskaya, and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1222. J. I. Musher, J. Amer. Chem. SOC.,1972, 94, 5662. C . H. Bushweller, H. S. Bilofsky, E. W. Turnblom, and T. J. Katz, Tetrahedron Letters, 1972,2401. R. G . Cavell, R. D. Leary, and A. J. Tomlinson, Inorg. Chem., 1972,11, 2578.

Physical Methods

257

Pyrex tubes showed line broadening, which was attributed to intermolecular fluorine exchange catalysed by products arising from the attack of (52) on the glass.55 It was not surprising that (53; Y = MeCEC) showed equivalent

F,C-P:

CF, I 'OSiMe, I

OSiMe,

F

1 F-P: I

Ph Ph

YP -:

F* I F

I* F

F

fluorine atoms at - 80 oC;6s however, it is interesting to note that two fluorine environments were detected for (53; Y = H) upon cooling the sample to - 140 0C.57 Calculations suggest that the square-pyramidal structure for tetrafluorophosphoranes is ca. 125 kJ mol-l higher than the trigonalbipyramidal structure (53). However, it has been estimated that association to form the dimer (54) would require only 25 kJ mol-1 and this could provide a route for Berry pseudorotation, i.e. (54) could dissociate to the monomer (55). Solvent could play a role similar to the second molecule of YPF4. This could explain the wide range of activation energies observed for these types of phosphoranes, e.g. hG* = 63 kJ mol-1 for (53; Y = NH,) but 38 kJ mol-l for (53; Y = NMe,), and < 17 kJ mol-1 for (53; Y = Me).58In Volume 1, p. 284, of these Reports it was suggested that one important factor which governs the barriers to pseudorotation is the presence of an equatorial substituent which could d,-p, bond to phosphorus. Support for this explanation has been obtained from a variable-temperature 19F n.m.r. study of the diaminotrifluorophosphorane (56), which showed restricted rotation of the NH, groups (see next section). The magnitude of the pseudorotation barriers relative to the P-N rotation barriers in (56) suggests that the resistance to P-N bond rotation may make a major contribution to the Berry rearrangement barrier in these m01ecules.~~ Slow exchange of the fluorine atoms attached to the phosphorus (*) atom in (57) is attributed to rigidity arising from the other phosphorus atom, which strongly favours the radial orientation for the methyl groups and apical orientation for the fluorine atom. 60Thevariable-temperature 66

sa 67

On O0

C. G. Moreland, G. 0. Doak, and L. B. Littlefield, J. Amer. Chem. SOC.,1973,95, 255. E. L. Lines and L. F. Centofanti, Inorg. Chem., 1973, 12, 598. A. H. Cowley and R. W. Braun, Znorg. Chem., 1973,12,491. J. 1. Musher, Tetrahedron Letters, 1973, 1093. E. L. Muetterties, P. Meakin, and R. Hoffmann, J. Amer. Chem. SOC.,1972,94, 5674. 0. Schlak, R. Schmutzler, R. K. Harris, and M. Murray, J.C.S. Chem. Comm., 1973,23.

0rganophosp horus Cheinistry

258

spectra of the spirophosphoranes (58) have been rationalized in terms of pseudorotationsl and a kinetic study of the epimerization and mutarotation of (59) indicated the possibility of an ee pseudorotation exchange of equatorial ligands. Restricted Rotation.-Slow rotation about the P-N bonds of (56) leads to cis and trans FPNH couplings. The lineshapes of the 19Fvariable-temperature spectra during the coalescence process compare favourably with those calculated for completely uncorrelated rotation of the two P-NH2 groups (i.e. there is no 'cog wheel' effect). The activation energy for P-N rotation was Restricted rotation is observed for the axial calculated to be 46.61 kJ m01-l.~~ CF, group in (51) when the compound is cooled to - 140 0C:54this is almost certainly a straightforward steric effect. At - 148 "C,slow rotation about the P-C bond of (60) is This gives a barrier (hG* =27.2 kJ mol-l) lower than that observed at - 109 "Cfor the t-butylamine (61) (AG * = 35.9 kJ m ~ l - l ) lH . ~ ~N.m.r. studies of the ylide (62) at - 100 "C showed no major Me,

Me/

,Me

C ../ I N Me

c '1

Me,P=NMe (63)

(61)

change in the spectrum; thus the barrier to rotation is less than 33 kJ mol-l. 1.r. studies indicated the barrier to be 8.62 kJ m ~ l - l The . ~ ~very low barrier supports the suggestion of Dewar et aLssthat it is always possible to select two hybrid d-orbitals on a four-co-ordinated phosphorus to match the orientation of the adjacent p-orbitals on the nitrogen atom. Variable-temperature studies of restricted rotation about the C-C bond in (63) gave AG* values in L. Beslier, M. Sanchez, D. Houalla, and R. Wolf, Bull SOC.chim. France, 1971, 2563. A. Klaebe, J. F. Brazier, F. Mathis, and R. Wolf, Tetrahedron Letters, 1972, 4367. J. B. Robert and J. D. Roberts, J. Amer. Chem. SOC., 1972, 94, 4902. C. H. Bushweller, W. G. Anderson, J. W. O'Neil, and H. S. Bilofsky, Tetrahedron Letters, 1973, 717. J. Bragin, S. Chan, E. Mazzola, and H. Goldwhite, J . Phys. Clwm., 1973, 77, 1506. M. J. S. Dewar, E. A. C. Lucken, and M. A. Whitehead, J . Chem. SOC.,1960, 2423; A. H. Cowley, M. J. S. Dewar, W. R. Jackson, and W. B. Jennings, J. Amer. Chem. SOC., 1970,92,5206.

259

Physical Methods

the range 69.0-76.9 kJ mol-l, but since this was the same as in the presence of traces of sulphuric acid, the barriers are believed to be due to the acidcatalysed Doubling of the H, resonance in the spectra of (64) has been attributed to rotational isomers.68

Ph3P\

4 0

/c-c,

R

40 C=C

H

Et

'

(63)

HA, ,HB

,H

(RO),P,

C ../ I P Ph PhCIlf 'COR

\

OAc

(65)

(64)

Inversion, Non-equivalence, and Configuration.-Coalescence of the HA and. HB resonances of (65; R = Me) and (65; R = CF,) at 118 and 55 "C,respectively, is attributed to phosphorus i n ~ e r s i o nHigher . ~ ~ barriers (AG* > 108 kJ mol-l) are claimed for (66), non-equivalenceof the methyl groups persisting at 190 O C 7 0 31PSpectroscopy has been used to study the configurations of (67),'l (68j,72 (69; Y = OH),73and (70).74The methylene group in (71) gives two Me,

Me,CH

,Me

..A /p\ CN

'idofg

Me,

\

/ \

Me2N

N H

Me

(66)

0 s

(69)

sII

RP-S-PR

I

F

(68)

sII

H,

I

,H

&OEt

F (70)

NH

,p\ / EtO S R-CH-CO,H

(67)

kp(

/p

,CH2-C

(MeO),P'

c'OH o (71)

doublets owing to the non-equivalence of the methylene protons. Hydrogenbonding is held responsible for holding the molecule in conformations which 67

To

74

C. J. Devlin and B. J. Walker, Tetrahedron, 1972, 28, 3501. V. V. Moskva, G. F. Nazvanova, T. V. Zykova, A. I. Razumov, A. B. Remizov, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.), 1972, 42,497. R. G. Kostyanovskii, Yu. I. El'natanov, L. M. Zagurskaya, K. S. Zakharov, and A. A. Fomichev, Bull. Acad. Sci., U.S.S.R., 1972, 21, 1841. R. G. Kostyanovskii, Yu. I. El'natanov, L. M. Zagurskaya, and K. S. Zakharov, Bull. Acad. Sci.,U.S.S.R., 1972, 21, 1844. R. Contreras, R. Wolf, and M. Sanchez, Syn. Znorg. Metal-org. Chem., 1973, 3, 37. T. A. Mastryukova, A. E. Shipov, M. S. Vaisberg, P. V. Petrovskii, E. I. Fedin, K . Shnaiders, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R.,1972, 21,443. M. Mikolajczyk and J. Luezak, Tetrahedron, 1972, 28, 5411. R. K. Harris, J. R. Woplin, M. Murray, and R. Schmutzler, J.C.S. Dalton, 1972, 1590.

260

OrganophosphorusChemistry

promote the non-equivalence. The non-equivalenceof the isopropyl groups in (72) was temperature dependent. The 31P signal of the ortho-tolylderivative(72; Ar = o-tolyl) appeared as a doublet of triplets. The triplet was attributed to overlapping doublet of doublets - arising from coupling to non-equivalent methines-and the doublet was attributed to the presence of two or more conformers. Comparison of calculated and observed linewidths suggested that the mechanism of conformer interconversion is complex, possibly as shown in Scheme 2.76The similarity of the fine splitting pattern of the 31Psignal of (69; 0

R!!

Me, ,Me L

I

I Pri

Pri

lt *

pq-$o

i r P ; $ q O r A

0

0 Scheme 2

Y = H) and the correspondingP-chloro-compound(69; Y

= C1) was taken as evidence that the two compounds had similar configuration^.^^ Two 31P signals (multiplets) were observed for (73). The possibility that they could be due to diasteriomers was thrown in doubt by the lH n.m.r. spectrum, which showed the compound to be largely en01ic.~~ The configurations of the bicyclic phosphoranes (74) were studied by lH n . ~ . r . ' ~

Spin-Spin Coupling.-The detection of hidden proton magnetic resonance signals by means of INDOR for AMX, ABX, and AXn spin systems and the 75

77

A. N. Pudovik, M. G. Zimin, A. A. Sobanov, L. I. Vinogradov, and Yu. Yu. Samitov, J . Gen. Chem. (U.S.S.R.), 1972, 42, 2163. P. E. Clark, K. D. Berlin, J. Mosbo, and J. G. Verkade, Phosphorus, 1973, 2, 265. W. Stec and M. Mikolajczyk, Tetrahedron, 1973, 29, 539. T. E. Snider and K. D. Berlin, Org. Prep. Proc. Internat., 1972, 4, 237. B. A. Arbuzov, Yu. Yu. Samitov, Yu. M. Mareev, and V. S. Vinogradova, Proc. Acad. Sci. (U.S.S.R.), 1972, 203, 717.

261

Physical Methods

effect of chemical exchange are reviewed.8oNickel chloride complexes of phosphines show complete absence of PH coupling in the phosphine and this can lead to useful simplification of the spectra. Collapsed multiplets are only slightly broadened and chemical shift changes are small.81 Overhauser enhancements have been used to study the stereochemistry and flexibility of the

I HO OH

HO OH

(75)

(76)

nucleotides (75)82and (76).83An improved method of modifying the HA 100 probe for heteronuclear double resonance is described.84 J(PP) and J(PM). Further examples of PIII-PIII and P1I1-PIV coupling constants in the range 235&35 Hz for diphosphine and diphosphine monosulphide groups have been reported,8sbut the disulphides have been found to give widely differing couplings, e.g. lJ(PP) is 187 Hz for (77; R = Me) but 118 Hz for (77; R = A very large PP coupling constant (766 Hz) has also been reported for (78).87 Quite large geminal PCP coupling constants (I 50 and 190 Hz) are obtained for the phosphino-phosphoranes(79; R = H or

Me);88vicinal PP coupling constants trans across a double bond as in (80; R = H) and (80; R = Et) are 61.6 and 77.7 Hz, respecti~ely.~~ Vicinal coupling It is interestacross a carbonyl group as in (81) reduces J(PP) to 16-18 HZ.~O ing to note some earlier work which was carried out on vicinal PP coupling. F. W. van Deursen, Org. Magn. Resonance, 1971, 3, 221. L. D. Quin, J. G. Bryson, and J. F. Engel, Phosphorus, 1973, 2, 205. T. D. Son, W. Guschlbauer, and M. Gueron, J. Amer. Chem. SOC.,1972, 94, 7903. 8 a W. Egan, S. ForsCn, and J. Jacobus, J.C.S. Chem. Comm., 1973, 42. O 4 H. J. C. Yeh, R. G. Tschudin, D. N. Lincoln, and E. Lustig, J. Magn. Resonance, 1973, 10, 235. a 6 F. G. Mann and A. J. H. Mercer, J.C.S. Perkin I, 1972, 1631, 2548. G. Hagele, R. K. Harris, and J. M. Nichols, J.C.S. Dalton, 1973, 79. *' H. Falius and M. Murray, J. Magn. Resonance, 1973, 10, 127. R. K. Harris, J. R. Woplin, K. Issleib, and R. Lindner, J. Magn. Resonance, 1972,7,291. L. Maier, Phosphorus, 1973, 2, 229. 0. T. Quimby, W. A. Cilley, J. B. Prentice, and D. A. Nicholson, J. Org. Chem., 1973, 38, 1867.

*o

262

0r.gariophosphori~sChemistry 0

II

(RO),P,

H'

,Cl

CH ,PO,Na

c= c,

I

COPO,Na,

The POCP coupling constant of (82; Y = Z = lone pair) is - 37.2 Hz. Methylation of the phosphite to give (82; Y = Me, Z = :) raises the coupling to 46.2 and methylation of the phosphine to give (82; Y = :,Z = Me)raises it further to + 114.6. Oxidation of both the P atoms to give (82; Y = Z = 0) gives a J(P0CP) of 139.1 H Z . ~ ~ An interesting phenomenon of spin-spin coupling was observed for P,F4BH3. Spin-spin coupling appeared when the temperature was increased. The effect is attributed to thermal decoupling by spin-lattice relaxation induced by the quadrupole of the boron nucleus at low t e m p e r a t ~ r e . ~ ~ Electronegative substituents can produce values for lJ(P=Se) of up to - 1100 Hz, but three alkyl groups can reduce it to the region of - 650 Hz. The magnitude is lower still for the alkylseleno-phosphorus bond, values for lJ(PSeR) being 477-453 Hz for (83), 341 Hz for (84; X = :), and - 205 Hz for (84; X = S).s3

+

+

x

Ii (Et 0 ),PSeE t (83)

X

hZ c P--Se ?4c (84)

I

J(PC). Triphenylphosphine has lJ(PC) of - 12.51 H Z . The ~ ~ negative direct bonding coupling constants and positive geminal coupling constants of phosphines are attributed to the formation of the P-C bonds from unhybridized p-orbitals of the phosphorus atom. This occurs when the valence s-orbitals are of lower energy than the p-orbitals, which makes hybridization unfavourable. Generally, for PIV compounds, the signs of lJ(PC) and 2J(PC)are positive and negative, respe~tively.~~ The geminal 31P-13C coupling constant in phospholes and phospholens is much larger than the vicinal 31P-13C coupling. Thus ,J(PC) for the 2-methyl compounds, e.g. (85), are in the range 17-22 Hz, but ~ ~ 13C spectra of some 3J(PC) for the 3-methyl compounds are 4-5 H z . The O1

O2 g3

D4

ss a6

R . D. Bertrand, D. A. Allison, and J. G . Verkade, J. Ainer. Chem. Soc., 1970, 92, 71. H. L. Hodges and R. W. Rudolph, Inorg. Chem., 1972, 11, 2845. D. W. W. Anderson, E. A. V. Ebsworth, G . D. Meikle, and D. W. H. Rankin, Mot. Phys., 1973,25, 381 ; W. McFarlane and D. S. Rycroft, J.C.S. Chem. Comm., 1972,902; W. J. Stec, A. Okruszek, B. Uznanski, and J. Michalski, Phosphorus, 1972, 2, 97. T. Bundgaard and H. J. Jakobsen, Acta Chem. Scartd., 1972, 26, 2548. F. J. Weigert and J. D. Roberts, Inorg. Chem., 1973, 12, 313. L. D. Quin, S. G . Borleske, and R. C. Stocks, Org. Magn. Resonance, 1973, 5, 161

263

Physical Methods

PIV heterocycles show that lJ(PC) is smaller for small rings and increased by electron-withdrawing groups on phosphorus ;the geminal coupling constant is useful for determining stereochemistry: thus 2J(PC)across the ring of (86) is about double that of the corresponding trans-i~omer.~~ The 13Cchemical shift . ~ ~ influence and lJ(PC) of (87) confirm that the a-carbon is sp2 h y b r i d i ~ e dThe Me&p,R

I1 0

N2

ArCPO(OMe), (8 7)

(86)

of the lone pair of electrons on 2J(PC) has been studied using substituted triaryl- and trithienyl-phosphines. Like J(PCH), the PCC coupling constant is largest when the carbon atom and phosphorus lone-pair of electrons are closest; thus (88; Y = Me or Hal) has 2J(PC-2)of 3055 Hz, but zJ(PC-6) is >2 H z . ~ The ~ observation of an unusually large "(PC) coupling constant (47 Hz) for the coupling between the bridgehead atoms of (89) suggests that the Karplus relation may apply to the correlation of 3J(PC) values.1oo

lJ(PH). The P-H coupling constant lol of the cyclic alkoxyphosphine (90) is 165 Hz, considerably less than that (203 Hz) for d,imethoxyphosphine.loz Calculations of the factors affecting lJ(PH) of phosphoryl and thiophosphoryl compounds (91) and (92) show that the change in nuclear charge accounts for only 10% of the observed change in coupling constant. Therefore the scharacter of the phosphorus orbital of the P-H bond is probably the main factor governing lJ(PH). In a plot of lJ(PH) against the total electronegativity of the P-substituents, the oxide curve possesses smaller couplings. This is attributed to greater back-bonding, which increases the s-character in the P-0 a-bond and decreases the s-character in the P-H bond. Replacing OEt by OPh decreased lJ(PH), probably for the same reasons.1o3A solvent dependence is observed for (91 ;R = Me, X = 0)and its deuterium derivative. A residual primary isotope effect in dilute cyclohexane solution was estimated G. A. Gray and S. E. Cremer, J. Org. Chem., 1972, 37, 3458. N. Gurudata, C. Benezra, and H. Cohen, Cunad. J. Chew., 1973,51, 1142. O Y S. Sorensen, R. S. Hansen, and H. J. Jakobsen, J. Amer. Cliem. SOC.,1972,94,5900. l o o R. B. Wetzel and G. L. Kenyon, J.C.S. Chem. Comm., 1973, 287. W. J. Stec, B. Uznanski, and J. Michalski, Phosphorus, 1973, 2, 237, 235. l o * L. F. Centofanti, Inorg. Chem., 1973, 12, 1131. l o 3 L. I. Vinogradov, M. G. Zimin, Yu. Yu. Samitov, and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1712. O7

On

264

Organophosphorus Chemistry

(91)

(92)

(93)

to be - 3.7 Hz.lo4The cyclic compound (93) has lJ(PH) of 600 Hz,lo5which is lower than the 640 Hz coupling for the acyclic compound (91 ;R = Et, X = S). The difference is greater between the di- and half-esters of (91; X = 0), lJ(PH) being ca. 700 and 600 Hz, respectively.loG J(PCnH). The geminal PCH coupling constants of dialkylvinylphosphines are quite low (1-5 Hz),lo7* lo*and even replacing the alkyl groups by chlorine does not increase the coupling very much, e.g. 6 Hz for (94).lo9The very large values of J(PCH) which occurs in the spectra of phospholenslo7 have also been observed for several phospholes, where J(PCH) is 33-41 HzV9 In contrast, the geminal coupling constants involving the corresponding PIv system (95) increase markedly as the electronegativity of the P-substituents increase. Inclusion of the PIv atom in a five-membered phospholen ll1 or phosphole ring system increases the coupling constant [J(PCH) is ca. 25 Hz for the cyclic phosphine oxides], but not as dramatically as occurs in the PIII system. In the heterocyclic oxides and salts (96; X = 0 or NH) the PCH coupling depends more on the nature of the substituents on phosphorus than on the nature of X.’13 y\

0

CI,P-CH=CHOEt (94)

II

Y pP- CH=CZ2 (95)

,R

Q (96)

W. McFarlane and D. S. Rycroft, Mol. Pliys., 1972, 24, 893. l o 6 D. A. Predvoditelev, D. N. Aranas’eva, Yu. B. Filippovich, and E. E. Nifant’ev, J, Gen. Chem. (U.S.S.R.), 1973, 43, 70. l o 6 A. Zwierzak and M. Kluba, Tetrahedron, 1973, 29, 1089. J. C. Tebby, in ‘Organophosphorus Chemistry’, ed. S. Trippett, (Specialist Periodical Reports), The Chemical Society, London, 1972, vol. 3, chapter 1I . loS R. G. Kostyanovskii, Yu. I. El‘natanov, and V. G. Plekhanov, Bull. Acad. Sci., U.S.S.R., 1971, 20, 2244. l o g V. V. Moskva, G. F. Nazvanova, T. V. Zykova, A. 1. Razumov, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 305. l 1 0 A. I. Razumov, V. V. Moskva, G. F. Nazvanova, and T. V. Zykova, J. Gen. Chem. (U.S.S.R.),1972, 42, 47; A. V. Dogadina, Yu. D. Nechaev, B. I. Ionin, and A. A. Petrov, ibid., 1971,41, 1670; M. S. Chattha and A. M. Aguiar, J. Org. Chem., 1973,38, Io4

ll1

11* 113

820. F. Kerek and G. Ostrogovich, Reti. Roumaine Chim., 1972, 17, 1881 ; H. M. Priestley and J. P. Snyder, Tetrahedron Letters, 1971, 2433. F. B. Clarke and F. H. Westheimer, J. Amer. Chem. Soc., 1971, 93, 4541. R. Fugnitto, M. H. Mebazaa, and M. Simalty, Conipt. rend., 1972, 274, C, 2206; M. Simalty and M. H. Mebazaa, Tetrahedron, 1972, 28, 3343; M. Maumy, Bull. SOC. chim. Fwice, 1972, 1600; M. H. Mebazaa and M. Simalty, Tetrahedron Letters, 1972, 4363.

265

Physical Methods

The vicinal PCCH coupling constant of the phosphine (97) is only 4.5 Hz.lf4

Two papers have appeared on the angular correlation of J(PCCH); one study was based on the 3- and 5-phosphorylated 1- and 2-pyrazolines, e.g. (50),51 the other study was based on a series of methyl phosphonates such as (98).l15 The angular dependence was used to distinguish the syn-epimer from the anti-epimer of (99)lls and the cis- and trans-isomers of the oxiran

8 I

Ph

(97)

0

(Et 0 )2P4’ Me’

‘C-,CHC02Et ‘O (1W

x OH PhZP,4 ,CHPh 1 C

II

CR2 (101)

Vicinal coupling constants in the range 17-24 Hz were observed for the system (lO1).lla The PHAcoupling1l@ in the ylide (102) was 13 Hz, but in the ylide (103) it was 5 Hz.12*Vicinal PCCH coupling involving the P V atom in

(105) 11’ 11*

G. MIrkl and H. Baier, Tetrahedron Letters, 1972, 4439. L. Evelyn, L.D. Hall, P. R. Steiner, and D. H. Stokes, Org. Magn. Resonance, 1973,5, 141.

116 11‘

H.Cohen and C. Benezra, Org. Magn. Resonance, 1973, 5, 205. A, N. Pudovik and R. D. Gareev, J . Gen. Chem. (U.S.S.R.),1972, 42,

1845.

M. Simalty and J. J. M. Ramos, Compt. rend., 1972, 274, C , 2105. l l @B. Bogdanovic and S. Konstantinovic, Synthesis, 1972, 481. leo Z. Yoshida, S. Yoneda, T. Yato, and M. Hazama, Tetrahedron Letters, 1973, 873. 118

266

Organophosphorus Chemistry

(104) was high (28.8 Hz),121but only 16 Hz in the oxyphosphorane (105).122 Conformational studies of (106) 123 and (107)124were made using the longrange 'W path' stereospecific coupling constants. One must remember, however, that very long-range coupling constants have been observed for phosphorus compounds which do not have a 'W' conformation, e.g. 7J(PH) is - 2.6 Hz for

J(PXCnH). The variations of J(P0CH) and J(HCCH) for derivatives of (109) with solvent and temperature can be rationalized on the basis that the ring possesses an envelope conformation and that the lone pair of electrons on phosphorus does not influence the coupling constant.126 The POCH and PNCH couplings for (110) are ~ e p 0 r t e d . lBoth ~ ~ of these coupling constants have the same sign (and similar magnitude, 8-11 Hz) in the PIV derivative (1 1 1).12* The angular dependence of J(P0CH) was used to determine the

n

o,p/o Y

n

0, ,NMe P I

conformational preferences of sugar and choline phosphates. 129 The spectra of the chalcogenide, borane, and metal derivatives of (112) show that J(POCH2) rises linearly with 6(CH2). Separate correlations are found for acceptors which are largely sigma in nature.130 The relative signs ofJ(POCnH) A. N. Pudovik, M. A. Pudovik, S. A. Terent'eva, and E. I. Gol'dfarb, J. Gen. Chern. (U.S.S.R.), 1972, 42, 1895. l a a I. Kawamoto, Y . Sugimura, N. Soma, and Y . Kishida, Chem. Letters, 1972, 931. p 3 T. Bottin-Strzalko and J. Seyden-Penne, Tetrahedron Letters, 1972, 1945. 1 2 4 A. B. Pepperman and T. H. Siddall, J. Org. Chem., 1973, 38, 160. l z 6 W. McFarlane, Org. Magn. Resonance, 1969, 1, 3. l P 6 R. H. Cox and M. G . Newton, J. Amer. Chem. Soc., 1972,94,4212. l a ' Yu. Yu. Samitov, M. A. Pudovik, A. I. Khayarov, and L. K. Kibardina, J. Gen. Chem. (U.S.S.R.), 1973, 43, 42. l s 8 J. Devilliers, J. Navech, and J. P. Albrand, Org. Magn. Resonance, 1971, 3, 177. l Z o J. Dufourcq and C. Lussan, F.E.B.S. Letters, 1972,26, 35; F . E. Hruska, D. J. Wood, R. J. Mynott, and R. H. Sarma, ibid., 1973, 31, 153. l a 0 D. A. Allison and J. G. Verkade. Phosphorus, 1973, 2, 257.

lz1

Physical Methods

267

for (1 13) are reported 1 3 1 and J(PHa) for (1 14) has been found to be 24 H Z . ~ ~ ~ The angular dependences of J(POCnH) have also been used to determine the preferred conformation of the enol phosphate (115).133 The rise in PH coupling constant [A3J(PH)]which occurs upon conversion of phosphites or thiophosphites to their oxides and sulphides increases with the number of P-S bonds (see Table 4). The sulphur compounds also show a

PIV Compound 3J(PH)/Hz A3J(PH)/Hz

(MeO),PO 11.1 0.1

Table 4 (MeO),PS

(MeS),PO

(MeS)J'S

13.6 2.6

15.6 5.7

17.8

7.9

regular decrease in "(PH) with increasing chain length of R.134This coupling constant increases from 9.9 Hz in (MeS),P to 12.3 Hz in (MeS),PF, but decreases when two fluorine atoms are introduced to 7.3 Hz for MeSPFz.135 Conformational changes may well be more important than the nature of the P substituent for determining the PIIISCH coupling constants because J(PSCH) of (1 16) remains fairly constant (0-2 Hz) for a wide range of substituents Y.136

The PNCH coupling constants in (117; Y = Cl) is 1.7 Hz to the PI11 atom and 15.6 Hz for the PIv atom; the charge on the PIv atom is decreased in (117; Y = NMe,) and this decreases 3J(P1VH)to 9.3 Hz but increases 3J(PIIIH) to 3.4 Hz.13' It is interesting to note that 2J(PNH) in P V compounds of the type (1 18) and (1 19) falls into two ranges, 17-20 Hz and 32-42 Hz. This may be associated with the apical or radial orientation of the nitrogen, or upon the J. P. Majoral, J. Navech, and K. Phhlaja, Phosphorus, 1972, 2, 1 1 1 . D. B. Denney and S. L. Varga, Phosphorus, 1973, 2, 245. l a S E. M. Gaydon, Tetrahedron Letters, 1973, 4469. l a l R. A. Shaw and M. Woods, Phosphorus, 1972, 1, 191. l S 6 R. Foester and K. Cohn, Inorg. Chein., 1972, 11, 2590. l a 6 J. P. Albrand, D. Gagnaire, J. Martin, and J. B. Robert, Org. Magn. Resonance, 1973, 5, 33. R. Keat, Phosphorus, 1972, 1, 253. lS5

268

Organophosphorus Chemistry

nature of the other atoms in the ring.138 No coupling was reported for the NH proton signal of the cyclic phosphine oxides (120; Y =Ph) and (120; Y = 0~t).139 Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies.-Relaxation times of tributyl phosphate have been studied 140 and have been used to calculate lifetimes of tributyl phosphate, phosphinate, and phosphine oxide in the solvent sheaths of uranyl nitrate complexes,141and to study preferential immobilization of parts of the 5-hydroxytryptamine molecule.142 Lanthanide shift reagents have been used to expand the spectra of AMP 143 and a phosphine sulphide; in the latter case, co-ordination probably occurred at an adjacent carbonyl g r 0 ~ p . A l ~review ~ of shift reagents 145 and a report on the effects of solvent on these reagents 146 have been published. Gd(fod), 14' and nickel chloridea1 have been found to be effective as spin-decoupling reagents. N.q.r. has been used to study conjugation effects of some dichlorophosphorus(rI1) compounds C1,PY (Y = R, RO, or R,N) 148 and to determine the structure of (121).140 An approximate linear relation has been found between 35Cl n.q.r. frequencies and P-CI bond lengths in chlorophosphazenes. The lower frequencies in the spectra of (122) were assigned to the apical chlorines.lS0 35ClN.q.r. and 14Nn.q.r. of the aminophosphines (123), which were obtained by a pulsed technique, showed that the dichloro- and diaminocompounds have non-equivalent C1 and N atoms, respectively. Calculated lS8

I3O 140 141

144 143 144

146

147

14@

R. Wolf, M. Sanchez, D. Houalla, and A. Schmidpeter, Compt. rend., 1972, 275, C, 151 ;Y. Charbonnel and J. Barrans, ibid., 1972,274, C, 2209; R. Mathis, M. Barthelat, L. Lopez, and J. Barrans, ibid., 1973, 276, C, 649. F. Mathey and J. P. Lampin, Tetrahedron Letters, 1972, 1949. A. A. Vashman and I. S. Pronin, Zhur. strukt. Khim., 1972, 13, 1008. A. A. Vashman, T. Ya. Vereshchagina, and I. S. Pronin, Zhur. neorg. Khim, 1972, 17, 471. T. Nogrady, P. D. Hrdina, and G. M. Ling, Mol. Pharmacol., 1972, 8, 565. G . R. Penzer, European J . Biochem., 1973, 34, 297. Y. Kashman and 0. Awerbouch, Tetrahedron, 1973, 29, 191. B. C. Mayo, Chem. SOC. Rev., 1973, 2, 49. J. Bouquant and J. Chuche, Tetrahedron Letters, 1973, 493. J. W. Faller and G. N. LaMar, Tetrahedron Letters, 1973, 1381. I. P. Biryukov, K. V. Nikoronov, E. A. Gurylev, and A. Ya. Deich, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1217. A. D. Gordeev, I. A. Kyuntsel, G . A. Golik, and V. A. Shokol, J. Gen. Chem. (U.S.S.R.), 1973, 43, 7. R. Keat, A. L. Porte, D. A. Tong, and R. A. Shaw, J.C.S. Dalton, 1972, 1648.

269

Physical Met hods

(1 22)

orbital populations suggest that the occupation of the N-lone-pair orbital is affected much more by the presence of a P-halogen atom than the conversion of a PIIr compound into its ~ha1cogenide.l~~ N.q.r. has also shown that the trichloromethyl group is apically disposed in the P V compounds (124). The 15N-H coupling constant of (124; Y = NH2) indicated the nitrogen to be sp hybridized.152 CCI

Y-P:

I I

c1

c1

2 Electron Spin Resonance Spectroscopy The e.s.r. spectra of y-irradiated solid trimethyl phosphite has been rationa 1 i ~ e d . Five l ~ ~ radicals are described, one of them analogous to the dimeric radicals (125) observed during the y-irradiation of phosphines at 77 K.154 Temperature dependence of the spectra of the radical cations (126) are attributed to boat-chair conformational changes.155The e.s.r. spectra and structures of phosphoranyl radicals derived from the reactions of t-butoxyl radicals with phosphine 156 and methylphosphines 15' have been studied. The variation of splitting with substitution is described. t-Butoxyphosphoranyl radicals have also been detected by chemical polarization of 31P nuclei.158 E.s.r. has been used to study the decomposition of phosphoranyl radicals derived from trimethyl and triethyl phosphite159and a series of primary, D. J. Osokin, I. A. Safin, and I. A. Nuretkinov, Org. Magn. Resonance, 1972, 4, 831. E. S. Kozlov, S . N. Gaidamaka, G. B. Soifer, Yu.N. Gachegov, and A. D. Gordeev, J. Gen. Chem. (U.S.S.R.), 1972, 42, 748. 1 5 8 M. C. R. Symons, Mol. Phys., 1972,24, 885. 1 5 4 A. R. Lyons and M. C. R. Symons, J.C.S. Faraday 11, 1972, 68, 1589. 1 5 5 R. D. Rieke, R. A. Copenhafer, A. M. Aguiar, M. S. Chattha, and J. C. Williams, J.C.S. Chem. Comm., 1972, 1130. l KP. 6J. Krusic and P. Meakin, Chem. Phys. Letters, 1973, 18, 347; K. U. Ingold, J.C.S. Perkin ZI, 1973, 420. l b P P. J. Krusic, W. Mahler, and J. K. Kochi, J. Atner. Chem. SOC., 1972, 94,6033. 158 Y. A. Levin, A. V. Il'yasov, E. I. Gol'dfarb, and E. I. Vorkunova, J. Gen. Chetn. (U.S.S.R.), 1972, 21, 1624. 1 5 0 G.B. Watts, D. Griller, and K. U. Ingold, J. Amer. Chem. SOC.,1972, 94, 8784; A. G. Davies, R. W. Dennis, D. Griller, and B. P. Roberts, J. Organometallic Chem., 1972, 40, 33C.

151

lSz

270

Organophosphorus Chemistry

secondary, and tertiary alkyl phosphites. 160 It was estimated that the structure of the phosphoranyl radicals (127) deviated from trigonal bipyramidal and become more square pyramidal as Y became more electropositive, i t . in the order F, Cl, OR, Me.lal Slow pseudorotation of the radical (128) at - 100 "C is reported.162A good correlation of the isotropic 31Psplittings of Y4P- with lJ(PH) of YIPH indicates that the odd electron occupies an orbital with hybridization similar to the phosphorus o-bonding orbital forming the P-H bond of the parent.ls3Em-. has shown that the initial radical derived from tris(dimethy1amino)phosphine ejects a dimethylamino-group and reacts with a further t-butoxy-group to form (129).164 OBut -p I -- -NMe,

I

NMe,

"Me, OBut

(128)

(129)

E.s.r. has been used to study the y-radiative decomposition of trimethylphosphine oxide under various conditions.165E.s.r. evidence has been presented which suggests that y-irradiated phosphate esters decompose to alkyl radicals by dissociative electron capture.166 3 Vibrational Spectroscopy The vibrational spectra of tripropynylphosphine (130),167 the fluoro- and chloro-derivatives of (1 3 l),lS8bis(trifluoromethy1)phosphines (1 32; Y = H or D),16uthe trimethylsilyl derivative (132; Y = Me3Si),170and tris(trifluor0methy1)phosphine(1 32; Y = CF3)171 have been analysed. The intensities of the P(C

CMe)

(1 30)

But,PX

(CFMY

(131)

(132)

1.'1600 skeletal vibrations have been compared for a series of aromatic tertiary phosphines 1 7 2 and the decrease of the v(C=O) band has been compared for a

A. G. Davies, D. Griller, and B. F. Roberts, J.C.S. Perkin ZZ, 1972, 2224, A. G . Davies, D. Griller, and B. P. Roberts, J.C.S. Perkin ZI, 1972, 993. I s a R. W. Dennis and B. P. Roberts, J . Organomctallic Chem., 1973, 47, 8C. I f i 3 A. G . Davies, R. W. Dennis, D . Griller, K. U. Ingold, and B. P. Roberts, Mol. Phys., 1973, 25, 989. 1 5 * R. W. Dennis and B. P. Roberts, J. Organometallic Chem., 1972, 43, 2C. I E 1 A. Begum and M. C. R. Symons, J.C.S. Faraday II, 1973, 69,43. l S 6 C. M. L. Kerr, K. Webster, and F. Williams, J. Phys. Chem., 1972, 76, 2848. I E 7 R. E. Sacher, B. C. Pant, F. A. Miller, and F. R. Brown, Spectrochim. Acta, 1972, =A, 1361. Ins R. R. Holmes, G. T. K. Fey, and R. H. Larkin, Spectrochim. Acta, 1973,29A, 665. l G 9 H. Buerger, J. Cichon, J. Grobe, and R. Demuth, Spectrochim. Acta, 1973, 29A, 47. S. Ansari, J . Grobe, and P. Schmid, J. Fluorine Chem., 1972, 2, 281. I 7 l H. Buerger, J. Cichon, J. Grobe, and F. Hoefler, Spectrochim. Acta, 1972, 28A, 1275. 1 7 * D . A. Yakutina, G. V. Ratovskii, B. V. Timokhin, and Yu. L. Frolov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1722.

lfio lf)l

271

Physical Methods 0

series of keto-phosphinimines (133) 17$and cyclic keto-ylides (134) and (135); the band was at lower frequency for ylides (134) than for the heterocyclicylides (135).174It has been suggested that the high frequency of v(C=O) in the heterocyclic ylide (136) compared with the 5,6-dihydro-derivative may be due to delocalization of x-electrons in the ring.175The i.r. spectra of the ketophosphonium salts were studied for evidence of en01ization.~~~ The carbonyl bands of the aromatic acid phosphides (137) appear in the 1650 cm-l ~egi0n.l'~

The position of the P=N bands of (138) appeared either in the region 11001200 or 1300-1500 cm-l, depending on the substituent on This band appears at 1297 cm-l in the spectra of (62). The P-N torsional mode at 112 cm-l was used to estimate the 8 kJ mol-1 rotation barrier about the P-N bond of (62).661.r. data are assigned for the compound (139)179and its chalcogenides.lEO 1.r. has also been used to study the co-ordination properties of methylphosphonic acid chlorides (140), l8 pyridylphosphonium esters

17a

174 176

177

17@ l*O

lS1

H. R. Kricheldorf, Synthesis, 1972, 695. G. Aksnes and H. Haugen, Phosphorus, 1972, 2, 155. M. Davies, A. N. Hughes, and S. W. S. Jafry, Canad. J. Chem., 1972,50, 3625. T. A. Mastryukova, I. M. Alajeva, H. A. Suerbayev, Y.I. Matrosov, and P. V. Petrovskii, Phosphorus, 1972, 1, 159. H. Kunzek, M. Braun, E. Nesener, and K. Ruehlmann, J. Organometallic Chem., 1973, 49, 149. ' E. S. Kozlov and S. N. Gaidamaka, J. Gen. Chem. (U.S.S.R.), 1972, 42, 101. K. Gosling and J. L. Miller, Inorg. Nuclear Chem. Letters, 1973, 9, 355. R. G. Cavell, R. D . Leary, and A. J. Tomlinson, Inorg. Chem., 1972,11,2573. A. N. Pudovik, A. A. Muratova, 1. Y. Kuramchin, and E. G. Yarkova, J. Gen. Cheni. (u.s.s.R.), i972,42,3oa.

272

Organophosphorus Chemistry

(141),lS2and phosphine amides (142),lS3and also the change with temperature of the equilibrium between (143) and (lU).ls* 0

II

Ph ,PNR (142)

P co' (RO),P-S' /rN Ph,C (143)

co

S

II

II

-,N

(RO),P-S,

Pht (144)

Vibrational analysis of methylphosphonic acid (145) 185 and of hydroxymethylphosphonate salts (146) l S 6are reported. In the latter case, (vOH)/ v(0D) was only 1.37. Particular attention was given to v(P-C) assignments in MeP03H, (145)

HOCH2P03Na,

H2O,P(CH,),LPO3H,

(146)

(147)

the spectra of the diphosphonic acids (147; n = 1-4 or 6).lS7The v(P0C) band of the cyclic phosphonic acid (148) assisted in its identification.ls8 Dimeric association of the phosphorylated benzoic acids (149) was deduced from the similarity of their v(0H) i.r. region with that of benzoic acid.lsgThe acids (149) cannot form intramolecular hydrogen bonds, as has been observed for the acetic acid derivatives (150) upon di1ution,lgoso the spectra also show (R0)ZPO I

HO,PNO\C/H

Q

an additional v(C=O) band at 1720-1740cm-1 due to the free carbonyl group. 1.r. studies indicate that strong hydrogen bonds are formed between the stabilized ylides (151) and phenol l g land between phosphine oxides and areneA. N. Speca, L. L. Pytlewski, and N. M. Karayannis,J. Inorg. Nuclear Chem., 1972,34, 3671. G . Vicentini and P. 0. L. Dunstan, J. Znorg. Nuclear Chem., 1972, 34, 1303; G. Vicentini and J. C. Prado, J. Inorg. Nuclear Chem., 1972, 34, 1309. L. I. Samarai, V. I. Gorbatenko, L. I. Kruglik, I. E. Boldeskal, and A. V. Kirsanov, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1160. l BB. 6J. Van der Veken and M. A. Herman, J . Mol. Structure, 1973,15,237; B. J. Van der Veken and M. A. Herman, J. MoE. Structure, 1973, 15, 225. l e a G. Brun and G. Jourdan, Conpt. rend., 1972, 275, C , 821. l e 7 L. Van-Haverbeke, H. 0. Desseyn, and M. A. Herman, Bull. SOC.chim. belges, 1972, 81, 547. l S 8 G . Brun and C. Rlanchard, Rev. Chim. mine'rale, 1972, 9, 453. l e OE. I. Matrosov, E. N. Tsvetkov, D. I. Lobanov, R. A. Malevannaya, and M. I. Kabachnik, J . Gen. Chem. (U.S.S.R.), 1972, 42, 1212. l S 0 E. I. Matrosov, E. W. Tsvetkov, R. A. Malevannaya, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1686. l o t J. Ekrene and T. Gramstad, Spectrochim. Acta, 1972, 28A, 2465.

lea

273

Physical Methods

sulphonamides. The latter adducts are believed to have the cyclic structure (152).lg2Hydrogen-bonding in a series of dithioic acids (153) has been studied at various temperature^.^^^ The use of an orientated single-crystal study has led to a revised assignment for the spectra of (154).19*Symmetric and asymmetric P-H stretching modes are observed in the spectra of the Pv compound (155). lg6

Stereochemical Aspects.-The i.r. spectra have been tentatively assigned for (156) on the assumption that the phosphines have a trans conformation in the solid and mixed trans and gauche conformations in The similarity of the spectra of the aminophosphine(157) in all phases from - 190 to + 150 "C without doubling of any peaks has led to the conclusion that only one conformer Calculations on this aminophosphine suggest the N atom is trigonal.fs8The diphosphine (158) populates two conformers in the fluid state but only the trans-conformer in the solid state.lg9The vibrational spectra and conformations of the heterocycles (159) 2oo and (1 60) 201 are discussed. The Me2NPF, (1 57)

(F3c)2p-p(cF3)2 (158)

n

@-.

/o

P

I

CI (1 59)

D. W. Allen, F. G. Mann, and J. C. Tebby, J.C.S. Perkin Z, 1973, 2793. R. R. Shagidullin, I. P. Lipatova, L. I. Vachugova, R. A. Cherkasov, and F. K. Khairutdinova, Bull. Acad. Sci., U.S.S.R.,1972, 21, 802. 1°* D. M. Adams and W. S. Fernando, J.C.S. Dalton, 1972, 2503. 1 0 6 L. F. Centofanti and R. W. Parry, Znorg. Chem., 1973, 12, 1456. l B 6 M. Bacci, Spectrochim. Acta, 1972, 28A, 2286. 1°' J. R. Durig and J. M. Casper, J. Cryst. Mol. Structure, 1972, 2, 1. l B 8I. G. Csizmadia, A. H. Cowley, M. W. Taylor, L. M. Tel, and S. Wolfe, J.C.S. Chem. Comm., 1972, 1147. 1 0 D J. D. Witt, J. W. Thompson, and J. R. Durig, Znorg. Chem., 1973, 12, 811. A. B. Remizov, R. R. Shaghidullin, D. F. Fazliev, and T. G. Mannofov, Optika i Spektroskopiya, 1973, 34, 252. = 0 1 J. P. Majoral and J. Navech, Spectrochim. Acta, 1972, 2814,2247. 108

1°8

K

274

Organophasphorus Chemistry

dependency of v(P-0) on conformation received particular attention.201 Combined Lr., dipole moment, and n.m.r. studies have been used to investigate the conformations of a wide range of phosphoryl compounds (161), i.e. phosphates and thiophosphates,202 p h o s p h ~ n a t e s ,phosphinates, ~~~ 204 and chloromethylphosphine oxides (162).205In some cases, although the i.r. spectra

(160)

(161)

(1 62)

showed no doubling of peaks the dipole moments indicated that mixtures of conformers were present. Conformational analyses of the keto-phosphoryl compounds (163) by i,r.206and by combined i.r,, n.m.r., and other physical methods are also 207 Studies of Bonding.-The use of vibrational spectra for determining the hybridization of o-bonds, the electronegativities and charges on P-bonded The methods of atoms, and the multiplicity of bonds to P has been reviewed.208 calculation of force constants of phosphorus compounds have also been discussed.209 The variation of v(PS) with calculated charge distributions in the sulphides (164) has been studied.210With regard to chlorophosphoranes such as (1 24 ; Y = Cl), it has been shown that fluorine or CF3have an influence on both the apical and radial P-Cl force constants.211

0. A. Raevskii, A. N. Vereshchagin, and F. G. Khalitov, Bull. Acad. Sci., U.S.S.R., 1972, 21, 305. 2 0 9 0. A. Raevskii, F. G. Khalitov, and T. A. Zyablikova, Bull. Acad. Sci., U.S.S.R., 1972, 21, 300. 0. A. Raevskii and V. D . Akamsin, F. G. Khalitov, and Yu. A. Donskaya, Bull. Acad. Sci.,U.S.S.R., 1972, 21, 2386; 0. A. Raevskii, F. G . Khalitov, and M. A. Pudovik, ibid., p. 161. 0. A. Raevskii, A. N. Vereshchagin, F. G. Khalitov, and Yu. A. Donskaya, Bull, Acad. Sci.,U.S.S.R.,1972,21,680; 0. A. Raevskii, F. G. Khalitov, A. N. Vereshchagin, and I. M. Vetluzhskikh, ibid., p. 2382. 2 0 1 A. B. Remizov, R. D . Gareev, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1972,42, 1232. * 0 7 B. N. Laskorin, V. V. Yakshin, and L. I. Sokal'skaya, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1256. 2 0 8 J. Goubeau, Chem.-Ztg., 1972, 96, 513. B. J. Van der Veken, H. 0. Desseyn, and M. A. Herman, Bull. SOC.chim. beiges, 1972, 81,555. 210 P. Castan, A. M. Alric, M. C. Labarre, and R. Turpin, J. Chim. phys., 1973, 70,411. * 1 1 K. Ramaswamy and B. K. Rao, Z . phys. Chem. (Leipzig), 1972, 246, 309. 202

Physical Methods

275

4 Microwave Spectroscopy The microwave spectra of (165) and its deuterium analogue are consistent with semiplanar structures and not the gauche conformation indicated by an electron diffraction study.212 The barrier to internal rotation of phosphine-borane, calculated from microwave data,213was 10.32 kJ mol-l, slightly less than the barrier estimated for methylphosphine-borane by CND0/2 calculations.214 The following theoretical studies relevant to microwave spectroscopic studies have been published. The moments of inertia of phosphiran have been calculated 215 from microwave bond angles and distances, and theoretical conformational analysis of cyclopropylphosphine (166) agrees well with conformations estimated by microwave spectroscopy.216 CND0/2 calculations of the barrier to methyl rotation in dimethylphosphine were in good agreement with experimental values.217Molecular Zeeman effects for HC=P and D C r P have been studied 218 and the structure of phosphorus oxytrichloride has been studied by microwave spectroscopy.219

5 Electronic Spectroscopy Conjugation effects in PII1 compounds, including U.V. spectroscopic evidence on dialkylarylphosphines, have been reviewed.220 Increasing the bulk of the alkyl group in a series of dialkyl(pheny1)phosphines (167) produced a small bathochromic shift but appreciable reduction in intensity for the 255 nm band.172The U.V. spectra of the p-nitrophenylphosphine (168) and its PIV derivatives are reported.221The introduction of an extra p-methyl group in the phospholes (169; Y = Me or C0,Me) produced a blue shift in both cases, in accordance with a steric interaction affecting conjugation by loss of p l a n a r i t ~ . ~ The electronic spectra of a series of phenylethynylphosphines (1 70) and their oxides demonstrate the powerful chromophoric properties of the phenylethynyl group.lo The auxochromic properties of various phosphorus groups on the styrene chromophore show maximum bathochromic effect by the C12P(S) *ls Ila

al* #15

ple 217

e21

P. Forti, D. Damiani, and P. G. Favero, J. Amer. Chem. SOC.,1973, 95, 756. J. R. Durig, Y. S. Li, L. A. Carreira, and J. D. Odom, J. Amer. Chem. SOC.,1973, 95, 2491. F. Crasnier, J. F. Labarre, and C. Leibovici, J. Mol. Structure, 1972, 14, 405. C. S. Hsu and I. C. Chang, Spectroscopy Letters, 1973, 6, 61. M. Pelissier, C. Leibovici, and J. F. Labarre, Tetrahedron, 1972, 28, 4825. G. Robinet, C. Leibovici, and J. F. Labarre, Chem. Phys. Letters, 1972, 15, 90. S. L. Hartford, W. C. Allen, C. L. Norris, E. F. Pearson, and W. H. Flygare, Chem. Phys. Letters, 1973, 18, 153. Y. S. Li, M. M. Chen, and J. R. Durig, J. Mol. Structure, 1972, 14, 261. E. N . Tsvetkov and M. I. Kabachnik, Russ. Chem. Rev., 1971, 40, 97. G. P. Schiemenz and H. U. Siebeneick, Phosphorus, 1972, 1, 179.

276

Organophosphorus Chemistry

group and the C1,P group.222A number of reports have been published on the electronic spectra of phosphinimines (171), some with extensive conjugation, ,Y

R (149)

e.g. (172). Variation of the phosphorus substituents in (171) had a relatively

small effect compared with variation of the N-phenyl s u b s t i t ~ e n t s The .~~~ maximum transmission of electronic effect through the phosphorus atom was obtained when one of the P-aryl groups was p - n i t r ~ p h e n y lIn .~~ the ~ more conjugated system (172) it was found that the spectra of the methylide derivative (172; Y = CH) had bands at much longer wavelength than the imine derivative (172; Y = N). The methylides were dark green, violet, or blue with a metallic lustre, but tended to be sensitive to The effects of varying Z22s and of protonating (172),,' have also been studied. The conjugative interaction between the benzene ring and the phosphoryl group in (173) was found to be low since a linear correlation between Amax and oowas observed.lll

(173)

(1 74)

The long-wavelengthabsorption of (174) and its rapid dimerization have been attributed to spiroconjugation.228U.V.spectroscopy has also been used in the ,~~~ 230 study of the keto-phosphoryl compounds (1 63),207g l y ~ e r y l pyridoxyl, R. R. Shagidullin, A. V. Chevnova, V. S. Galeev, and Ya. A. Levin, Bull. Acad. Sci., U.S.S.R., 1971, 20, 1082. I. N. Zhmurova, R. I. Yurchenko, V. G. Yurchenko, A. A. Tukhar, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972,42,770; I. N. Zhmurova, V. G. Yurchenko, A. P. Martynyuk, and A. V. Kirsanov, ibid., p. 1042. T. G. Edel'man and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1469. R. I. Yurchenko, I. N. Zhmurova, L. N. Shpartun, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2350. I. N. Zhmurova, V. G. Yurchenko, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1938. I. N. Zhmurova, R. I. Yurchenko, V. P. Kukhar', L. A. Zolotareva, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1947. J. M. Holland and D. W. Jones, J.C.S. Perkin Z, 1973, 927. J. Greenwald and M. Halmann, J.C.S. Perkin IZ, 1972, 1095. N. P. Bazhulina, A. Ya. Lomakin, Yu. V. Morozov, F. A. Savin, L. P. Cherkashinn, and M. Ya. Karpeiskii, Biophysirs, 1971, 16, 847.

Physical Methods

277

and p o l y - p h ~ s p h a t e s and , ~ ~ ~butyl phosphate-phenol hydrogen-b~nding.~~~ A comparison of the absorption and fluorescent spectra of phenylphosphinic acid with those of benzoic acid indicates that the valence shell expansion of phosphorus is weak in the thermally relaxed lowest excited The photoelectron spectra of phosphabenzene (175) have indicated inversion of a2(n) and bl(n) orbitals between pyridine and phosphabenzene. This interpretation is now supported by MO calculations. There is little change in the energy of the a2(n)orbital since this orbital has nodes at the heteroatom. The inversion arises from the large lowering of the b orbitals in pyridine owing to the strong electron-acceptingnature of the nitrogen atom.234The ionization potential of MePH, is lower than that of SiH3PH2,in accordance with donation of the lone pair of electrons into the d-orbitals of silicon.236 The difference between the p.e. spectra of (176) and CH3-Y (Y = cyclopentadiene, CN,

NCO, NR2, etc.) has been attributed to the difference in electronegativity of PF2 and CH3 and possibly R withdrawal involving the 3d-orbitals of phosp h o r ~ P.e. ~ . spectra ~ ~ ~ of PhPCl,, (177; Y = Me, Z = Cl), and (177; Y = Z = Me2N),as well as a number of phosphites, phosphates, and pesticides, have been analysed.237 The bonding energies of cyclotriphosphazenes decrease as Me,N groups replace chlorine. The 1s binding energies of the ring nitrogens are less than those of theexocyclicnitr~gens.~~~ Spectra from powdered calcium salts of phosphoric and phosphorous acids showed that X-ray photon emission spectroscopy will differentiatenon-identical but otherwise very similar ligands, e.g. P-0 and P-OH.23D Core-level binding-energy shifts from X-ray photoelectron spectra have been used to obtain information on the charges on atoms in molecules. An attempt has now been made to extend this technique to study the stereochemistry of PF5. The apical fluorine atoms are expected to carry more negative charge and therefore have lower core-level binding energies. Although the spectrum is not clearly resolved, it coctains one asymmetric peak whose shape is consistent with two apical fluorines.240 Calculated pee. 181

asa aaa

1s7

M. Bennoson and D. J. Williams, J. Phys. Chem., 1972,76,3673. S . M. Petrov, V. S. Pilyugin, Z. A. Eredzhepova, and F. A. Fatkullina, J. Gen. Chem. (U.S.S.R.), 1972, 42, 754. S. G. Schulman and P. Liedke, Analyt. Chim. Acta, 1973, 63, 197. C. Batich, E. Heilbronner, Y. Hornung, A. J. Ashe, and D. T. Clark, J. Amer. Chem. Sac., 1973, 95, 928. S. Cradock, E. A. V. Ebsworth, W. J. Savage, and R. A. Whiteford, J.C.S. Faraday 11, 1972, 68, 934. S. Cradock and D. W. H. Rankin, J.C.S. Faraday II, 1972, 68,940. D. Betteridge, M. Thompson, A. D. Baker, and N. R. Kemp, Analyt. Chem., 1972,44, 2005.

238 a80

24u

B. Green, D. C. Ridley, and P. M. A. Sherwood, J.C.S. Dalton, 1973, 1042. K. Myers and G. Andermann, J . Phys. Chem., 1972,76, 3975. R. W. Shaw, T. X. Carroll, and T. D. Thomas, J. Amer. Chenz. SOC.,1973, 95, 2033.

278

Organophosphorus Chemistry

diagrams for PF3241 and the estimation of phosphorus and organophosphorus compounds by ~ ~ l o ~ r i m e t spectrophot~metric,~~~ ri~,~~~ and emission spectrometry 2 4 4 are reported. 6 Rotation and Refraction The application of circular dichroism to the determination of the configuration of phosphorus thioic acids has been examined in some detail. The correct sign of rotation of the sodium D line is predicted by Brewster’s conformational asymmetry rule, and the sign of the Cotton effect (200-230 nm) is predicted by a ‘planar rule’. Evidence has been obtained for the presence of the tautomeric Dextrostructure (178) when the acids are dissolved in a non-polar rotatory 0-alkyl alkylphosphonothioic acids have the R configuration.246 Optical rotation was used to estimate the absolute configuration of (179).247 Circular dichroism is strongly modified upon acidification of the solution and this has been used on very small amounts of compound to determine protonation equilibria of weak bases such as (180).248The conformation of UMP has also been studied by c.d. s p e ~ t r o s c o p y . ~ ~ ~

Ph

I

x\

Y-P=S 2’ (1 80)

(181)

Ph (1 82)

(183)

A magneto-optical study of aminophosphines and their oxides indicates that there is competition between the 0 and N atoms for n-bonding in the oxides

242

24a

244 246

24e t47

*48

L. J. Aarons, M. F. Guest, M. B. Hall, and I. H. Hillier, J.C.S. Faraday 11, 1973, 69, 643. A. M. Maksudov, U. Tadzhibaev, and S. T. Akramov, Uzbek. khim. Zhur., 1973, 17, 16. E. A. Druyan, Gigiena i Sanit., 1972, 37, 100. G. F. Kirkbright, A. F. Ward, and T. S. West, Analyt. Chim. Acta, 1972, 62, 241. M. Mikolajczyk, M. Para, J. Omelanczuk, M. Kajtar, and G . Snatzke, Tetrahedron, 1972,28,4357. M. Mikolajczyk, J. Omelanczuk, and M. Para, Tetrahedron, 1972, 28, 3855. R. Contreras, J. F. Brazier, A. Klaebe, and R. Wolf, Phosphorus, 1972, 2, 67. P. Bonvicini, A. Levi, and G. Scorrano, Gazzetta, 1972, 102, 621. C. Formoso, Biochemistry, 1972, 11, 4031.

279

Physical Methods

and that the n character is dependent on the effective electronegativity of the phosphorus atom.250A similar study on a wide spectrum of sulphides (181) indicated that the P-S bond character is constant whereas the charges on these two atoms vary significantly.210 7 Diffraction

X-Ray diffraction of the diphosphorin (182) showed that it exists as the half(1 83) possesses chair form, as found in c y c l ~ h e x e n eThe . ~ ~diphosphonia-salt ~ a boat conformation which is slightly flattened compared with the hexaphenyl derivative.252 The cis geometry of the ester-stabilized ylide (184), with partial double-bond character for PC, CC, and CO is in accordance with n.m.r. conclusions. The allylic phosphonium salt (185) has the 3-methyl group

pointing back towards the phosphorus atom in the crystal, which allows the bulkier C-6 side-chain to occupy the less hindered An interesting vinylphosphonium salt (1 86), which has two mesomerically donating atoms bound to the /3-carbon, has its P-C, N-C, and 0-C bond lengths shortened and its a/3 C=C bond lengthened. Thus it appears there is considerable backbonding to the d-orbitals of phosphorus and that the canonical form (187) con-

1

H

tributes significantly to its The structure of (188; X = Br) and (188; X = C1) are very similar. The only discernible difference is the slightly longer P-C bonds in the former.256Crystal structures of the diphosphonic zbo

zal

zsz z5s

25p

z56

M. C. Labarre and Y . Coustures, J. Chim. phys., 1973, 70, 534. F. Sanz and J. J. Daly, Phosphorus, 1972, 2, 135. L. D. Cheung and L. M. Trefonas, J. Heterocyclic Chem., 1972, 9, 991. V. D. Cherepinsii-Mol, G . G . Aleksandrov, A. I. Gusev, and U. T. Struchkov, Zhur. strukt. Khim., 1972, 13, 298. J. Hjortas, Acra Cryst., 1973, B29, 767. L. M. Trefonas and J. N. Brown, J. Heterocyclic Chem., 1972,9, 985. W. Dreissig, K. Plieth, and P. Zaske, Acra Ct-ysr., 1972, B28, 3473, 3478.

280

Organophosphorus Chemistry

acid (189)257 and the complex (190) 258 are also reported. The Ph,N-C group in (191) was unexpectedly planar.259A study of the crystal structures of (192) and (193) showed that the P-N bond length shortens with increased formal Ph Ph pP

'C-C' Ph BP

\N-Ph \NPh

2 ph2p\N/PPh2 H

S

/p It

c1'p\,7c12 Ph

positive charge on the phosphorus atom; the nitrogen atoms are nearly planar.26oThe P-N bond lengths in (194) are equal in length and the ring is planar.261A slight chair form is reported for cyclotriphosphazatriene (195). Shortened P-N bonds and lengthened P-C1 bonds indicate charge transfer from nitrogen to chlorine when they are gemina1.262 A similar conclusion was obtained from a study of the tetraphosphazene (196; Y = NMe,).263The

t 194) tetraphenyl derivative (196 ;Y = Ph) has also been studied.264 Conformational information was sought from the X-ray crystallographic studies of ATP 2 6 s and AMP derivatives.266 The tetrathiophosphorane (197) is distorted from the 267

a68

26x

peK 16e

D. De La Matter, J. J. McCullough, and C. Calvo, J. Phys. Chem., 1973, 77, 1146. S. Z. Goldberg, E. N. Duesler, and K. N. Raymond, Inorg. Chem., 1972, 11, 1397. F. K. Ross, L. Manojlovi'c-Muir, W. C. Hamilton, F. Ramirez, and J. F. Pilot, J. Amer. Chem. SOC.,1972,94, 8738. K. M. Ghouse, R. Keat, H. H. Mills, J. M. Robertson, T. S. Cameron, K. D. Howlett, and C. K. Prout, Phosphorus, 1972, 2 , 4 7 . M. B. Peterson and A. J. Wagner, J.C.S. Dalton, 1973, 106. F. R. Ahmed and D. R. Pollard, Acta Cryst., 1972, B28, 3530. G. J. Bullen and P. A. Tucker, J.C.S. Dalton, 1972, 2437. G. J. Bullen and P. A. Tucker, J.C.S. Dalton, 1972, 1651. D. Perahia, B. Pullman, and A. Saran, Biochem. Biophys. Res. Comm., 1972,47, 1284. M. Sundaralingam and J. Abola, J. Amer. Chem. SOC., 1972,94,5070; S . M. Hecht and M. Sundaralingam, ibid., p. 4314.

28 1

Physical Methods

trigonal-bipyramidal structure, the 'apical' and 'radical' P-S bond lengths being ca. 220 and 214 pm.267A distorted trigonal-bipyramidalstructure is also observed for the tetrafluorophosphoranes (198). A short P - 4 bond suggests

d,-p, bonding, and the narrowing to 108.1' of the angle between the pseudoradial fluorine atoms could be a consequence of increased electron density in the C-P bond.2ss CND0/2 calculations on difluorodiphosphine support the trans-conformation (199).269 There has been a considerable increase in the number of electron diffraction studies. Electron diffraction data on the amino-phosphines (200) and (201) show that the tris(dimethy1amino)-derivative (200) is close to being

(199)

(2@3

(201)

planar whereas the ethylenamino-derivative(201) is pyramidal. Although nonbonding interactions in (201) is less, it has the longer PN bond (175 pm) compared with (200) (170 pm).270The data on the chlorophosphite (202) are in best accord with an envelope hetero-ring with an axial chlorine,271and the data on (203) support a chair conformation with an axial chlorine.272A brief report on phenyldichlorophosphine has also been published.273 Electron diffraction studies have also been carried out on the silylphosphines (204) 274 I

R:YP

H,SiPR2 f3nA)

867

lea

*ID

a70

171

174

M. Eisenhut, R. Schmutzler, and W. S. Sheldrick, J.C.S. Chem. Comm., 1973, 144. M. J. C. Hewson, R. Schmutzler, and W. S. Sheldrick, J.C.S. Chem. Comm., 1973, 190. M. C. Bach, F. Crasnier, J. F. Labarre, and C. Leibovici, J. Mul. Structure, 1972, 13, 171. L. V. Vilkov, L. S. Shaikin, and V. V. Evdokimov, Zhur. strukt. Khim., 1972, 13, 7 . B. A. Arbuzov, V. A. Naumov, S. A. Shaidulin, and E. T. Mukmenev, Proc. Acad. Sci. (U.S.S.R.), 1972, 204, 457. V. A. Naumov and N. M. Zaripov, Zhur. strukt. Khim., 1972, 13, 768. V. A. Naumov, N . M. Zaripov, and N . A. Gulyaeva, Zhur. strukt. Khim., 1972,13,917. C. Gildewell, P. M. Pinder, A. G. Robiette, and G. M. Sheldrick, J.C.S. Dalton, 1972, 1402.

282

Organophosphorus Chemistry

and (205).275The gas phase of chloromethylthiophosphonous dichloride is estimated to contain equal populations of the conformers (206) and (207).276

F,P-NHSiH (205)

(206)

(207)

It has been found that all the bond lengths decrease (P-Fapical most) as the number of fluorine atoms in the fluorophosphoranes (208) increases;277the methyl groups are freely rotating.

8 Dipole Moments, Conductance, and Polarography There has been a substantial increase of papers in which dipole moment studies are included. Studies of alkylphosphines (209) indicate that the lone-pair moments are fairly constant and that the changes in dipole moments are best explained by changes in P-R bond moments. Plots of bond moment against number of P-R bonds give separate lines for odd- and even-chain alkyl groups. The changes could not be correlated with inductive effects.278This is supported by a comparison of the dipole moments of methylphosphine-boranes and methylamine-boranes. A correlation between the two was only obtained after correction for the lone-pair contribution in the amines. 279 A theoretical study of phosphine indicates that the participation of d-orbitals lowers the dipole moment and could reverse it.28oComparison of measured and calculated moments for the arylphosphines (210) suggests that the interaction of the n-orbital of phosphorus with the n-system is weaker than in the amines (211).%*1 The higher moment of 2.28 D for (212; X = Cl) compared with 2.04 D for (212; X = Br) may be due to d,-p, bonding to the PIIratom.282Simple vector analysis was sufficient to explain the relative dipole moments of mixed tria76

z7*

17’ z78

a81

D. E. J. Arnold, E. A. V. Ebsworth, H. F.Jessep, and D. W. H. Rankin, J.C.S. Dalton, 1972, 1681. L. S . Khaikin, L. V. Vilkov, A. F. Vasil’ev, N. N. Mel’nikov, T. F. Tulyakova, and M. G. Anashkin, Proc. Acad. Sci. (U.S.S.R.), 1972, 203, 349. H. Yow and L. S. Bartell, J. Mol. Structure, 1973, 15, 209. J. G. Morse and R. W. Parry, J. Chem. Phys., 1972, 57, 5367. J. G. Morse and R. W. Parry, J. Chem. Phys., 1972, 57, 5365. J. B. Robert, H. Marsmann, L. J. Schaad, and J. R. Van Wazer, Phosphorus, 1972, 2, 11. H. Goetz, B. Klabuhn, F. Marschner, H. Juds, and A. Wahid, Phosphorus, 1973,2,221. N. Saraswathi and S. Soundararajan, J. Organometallic Chem., 1972, 46, 289.

Physical Methods

283

halogenopho~phines.~~~ Dipole moments of the Z and E geometric isomers of Dipole moments also the vinyl compound (213) have been RCH,

\ c1/C=CHPoC‘2

(2 12)

(21 1)

(213)

support the concept that d,-p, conjugation is a competitive process. Conjugation with the vinyl group in (214) decreases as competition from the groups Y increases.285d-Orbital competition has also been studied in a series of aminocompounds (215; Y = NR2, C1, OR, F, or R).286 There have also been many conformational studies using dipole moments. In the dithioic acids and esters (216) the gauche conformation prevails, in

agreement with the concept of the maximum number of gauche interactions between polar Studies in combination with i.r. spectroscopy were discussed in Section 202-206 The plot of log ,u against X Hammett 0 gave a straight line with a negative slope, which suggests that the dipole moments increase with electron-releaseby substituents.288Calculated dipole moments of fluorophosphoranes,289on the assumption that the bonds shorten as the humber of F atoms increases, were in good agreement with observed values, thus supporting the electron diffraction studies.2 7 7 Conductance studies of dissociation have been carried out on adducts of bipyridyl and PI11 compounds. Dissociation occurs in acetonitrile when P-C1 groups are present. Stability constants indicate that the phosphorus compounds act as electron acceptors through the 0 electronic system.290Dissociation of adducts of lanthanides and (142; R = H or Me) depend upon the lanthanide Conductance has also been used to study the transport mechanism of phosphonic acid 3 . 7 6 p

286

189

J. G. Morse and R. W. Parry, J. Chem. Phys., 1972, 57, 5372. A. V. Dogadina, K. S. Mingaleva, B. I. Ionin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2183. E. A. Ishmaeva, R. D. Gareev, G. E. Yastrebova, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 70. M. C. Labarre and Y . Coustures, Compt. rend., 1973, 276, C , 133. 0. Exner, L. Almasi, and L. Paskucz, COIL Czech. Chem. Comm., 1973, 38, 677. D. M. Petkovic, B. A. Kezele, and D. R. Rajic, J. Phys. Chem., 1973, 77, 922. C. Brun, F. Choplin, and G. Kaufmann, Znorg. Chem. Acta, 1972, 6, 77. K. Tanaka and T. Tanaka, Znorg. Chim. Acta, 1972, 6,467. R. A. Wallace, J. L. Crowley, and N. V. Vijayraghavan, J. Polymer Sci., Part A-1, Polynier Chem., 1972, 10, 3447.

284

OrganophosphorusChemistry

Polarography of triphenylphosphonium salts indicates ylide formation by the following equation :2ga

+

Ph,P-CHR,

+ e- +3Ph3P=CR2 + 3 Ph3P + CH2R,

The diphosphoniacyclohexanes(217), (218), and (219) show a dramatic shift in the reduction potential as the number of double bonds are increased. This has been attributed to substantial d,,-pn bonding in the unsaturated salts. It is suggested that diphosphabenzene (220) was generated in the reduction of (219).293 Polarographic studies are also reported on the sulphonamide derivatives of (221) 294 and some polypho~phates.~~~

Ph

I

J-P f)h\

I

Ph

9 Mass Spectrometry The time average of 2000 plots of ionization against electron energy gave29s an ionization energy of 1O.OeV for PH3+, in good agreement with photoelectron spectra. The mass spectra of the triphosphine (222) and its mono-, di-, and tri-sulphide have been i n t e r ~ r e t e dThe . ~ ~ mass spectral fragmentation of

(223)

(224)

loS

J. M. Saveant and S. K. Binh, Bull. SOC.chim France, 1972, 3549. R. D. Rieke, R. A. Copenhafer, A. M. Aguiar, M. S. Chattha, and J. C. Williams,

‘O’

J. Electroanalyt. Chem. Interfacial Electrochem., 1973, 42, 309. G. A. Supin, A. L. Itskova, and Ya. A. Mandel’baum, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1 1 82. S. Shaw and A. Townshend, Talanta, 1973,20,332; F. Al-Sulimany and A. Townshend, Analyst, 1973, 98, 34. J. D. Morrison and J. C. Traeger, J . Mass Spectrometry Ion Phys., 1973, 11, 277.

Ioa

285

Physical Methods

(223; X = 0) and (223; X = S) differ in that the former rearranges to (224) before losing ArPH, whereas (223 ; X = S) rearranges to (225) and then loses

(225)

ArS.297The mass spectra of some five-membered cyclic phosphites gg8 and triphenyl phosphite 299 are reported. In the latter case the fragmentation pattern

/ ' 0P+

base peak

Scheme 3

is described in Scheme 3. Several difluorophosphines300 and the dichlorophos+ phine (226) give P(Hal), as the base peak. 301 In the negative ion spectra, stable ions such as Hal- or CN- tend to dominate the spectra.300The rearrangement of (227) to the phosphabenzene (228) was shown to be intermolecular by mass At-,

,At-

(i I

CH,Ar (227)

*OO

*01

I. Granoth, J. B. Levy, and C. Symmes, J.C.S. Perkin IZ, 1972,697; W. D. Weringa and I. Granoth, Org. Mass Spectrometry, 1973,7,459. U. Y . Efremov, R. Z. Mysin, L. I. Gurarii, and E. T. Mukmenev, Khim. geterotsikl. Soedinenii, 1972, 1329. V. N. Bochkarev, A. N. Polivanov, E. F. Bugerenko, V. I. Aksenov, and E. A. Chernyshev, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2345. D. W. H. Rankin, P. W. Harland, and J. C. J. Thynne, Inorg. Nuclear Chem. Letters, 1972, 8, 1101 ; P. W. Harland, D. W. H. Rankin, and J. C. J. Thynne, Inorg. Chem., 1973,12, 1442. A. R. Davies, A. T. Dronsfield, R. N. Haszeldine, and D. R. Taylor, J.C.S. Perkin I , 1973, 379.

286

Organophosphorus Chemistry

spectral examination of the products from mixed phenyl and tolyl compounds. 302 Phosphonium halides readily lose HHal in the mass spectrometer and molecular ions are often not seen.3o3Fragmentation in the negative ion spectra of the ylide (229) begins with the loss of triphenylphosphine or a phenyl radical. The cyclic ion (230) appears in the spectra, but there are several abundant non-phosphorus-containing ions.3o4 Mass spectra of stabilized arsenic ylides are similar to the phosphorus ylide~.~O~ The mass spectra of the The cyclic diphosphinic ester (231) shows loss of Me, RCHO, and HP02.306

Ph,P=C

TOMe \

greater ease with which the P-C bonds of l-adamantane derivatives are cleaved to give tertiary adarnantyl ions was used in mass spectral studies to distinguish between the l-adamantaneester [232; Y = PO(OMe),, Z = HI and Mass spectral studies the 2-adamantane ester [232; Y = H, 2 = PO(OMe)2].307

are also reported for (233) 308 and (234).309In a comparison of the fragmentation of alkoxy- and alkylthio-phosphate esters (235) it was found that the sulphur-containing compounds gave more abundant molecular ions and that the radicals containing phosphorus and sulphur had lower ionization potentials than those containing phosphorus and oxygen. The methylthio-compounds had a strong tendency to lose MeS radicals in addition to the loss of CH,S. lo

808

807

G . Mark1 and D. E. Fischer, Tetrahedron Letters, 1973, 223. K. C . Srivastava and K. D. Berlin, J. Org. Chem., 1972, 37, 4487; T. E. Snider and K. D . Berlin, ibid., 1973, 38, 1657. R. G . Alexander, D. B. Bigley, and J. F. J. Todd, J.C.S. Chem. Comm., 1972, 553. A. J. Dale and P. F r ~ y e n Phosphorus, , 1973, 2, 297. N. B. Karlstedt, M. V. Proskurnina, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1972,42, 2412. E. S. Shepeleva, P. I. Sanin, D. M. Oleinik, E. I. Bagrii, and A. A. Polyakova, Proe. Acad. Sci. (U.S.S.R.), 1972, 203, 275. T. Nishiwaki, Org. Mass Spectrometry, 1972, 6, 693. Y. Ogata, Y. Izawa, and T. Ukigai, Bull. Chem. SOC.Japan, 1973, 46, 1009. E. Santoro, Org. Mass Spectrometry, 1973, 7 , 589.

287

Physical Methods

(MeX),PX (235)

CH ,OSiMe

CHzOzCR

CHOSiMe,

CHOZCR

CH,OPO,Me,

CH,OPO,CH ,CH

I

I

(236)

I I

,A Me,

(237)

Studies using lSO and the deuterium-labelled silylated glycerol phosphate (236) showed that although extensive intramolecular rearrangements of the SiMe, and OSiMe, groups occurred, it was possible to measure the position and abundance of l80at each oxygen position.311Fragments arising from the amino-alcohol moiety of (237) have been identified in low-voltage spectra. Metastable ions which have a low half-life (but above 3 p)were detected by scanning the first field-free region.312Further work on the mass spectra of cyclic triarylphosphines has been reported, together with a description of the fragmentation of pentaphenylphosphorane and the corresponding bisbiphenylenephosphoranes (238 ; R = Me or Ph).313 Pentaphenylphosphorane readily loses two phenyl groups to give prominent peaks at 262 and 260 mass units. This fragmentation was much less important for (238), whose spectra showed abundant ( M - 1) and ( M - R) ions. Formation of doubly charged ions characterized the spectra of (238; R = Me).313

(239)

10 pK and Thermochemical Studies

The PKa values of some phosphinylated and phosphorylated phenols (239) show that all the P substituents are n-electron acceptors from the phenol ring, even in the case of the Me,P group. Thus donation from the hydroxy-group appears to inhibit donation by the Me,P group.314A PKa study has shown that there is little difference in the effectiveness of the phosphino-group of (240; X = lone pair) and the phosphoryl groups of (240; X = 0) to transmit the . ~ ~pKa ~ values of electronic effects of a nitro-group Y to the a m i n o - g r o ~ pThe ala 31s s14

al6

R. M. Caprioli and E. J. Heron, Biochirn. Biophys. Acta, 1973, 296, 321. R. A. Klein, J. Lipid Res., 1972, 13, 672. D. Hellwinkel, C. Wunsche, and M. Bach, Phosphorus, 1973,2, 167. E. N. Tsvetkov, M. M. Makhamatkhanov, D. I. Lobanov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 761. L. I. Chekunina, A. I. Bokanov, and €3. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1972, 42, 105.

288

Organophosphorus Chemistry

(240)

(241 ;Y = Ph,P=N-) and (241 ;X = NR2, Me, or F) have been compared and correlated with a.316 p-Nitrobenzyltriphenylphosphoniumperchlorate is useful as a reference acid for the determination of PKa values in the range 15-21. The concentration of the ylide produced is readily estimated using the A,, at 510 nrn.,17 The closeness of the PKa values in the ylide series (242) has led to the suggestion that protonation occurs on oxygen.318The protonated species of the diphosphine dioxides (243) is probably (244), since the butyric acid group in

(241) (242) (243) [243 ;R = (CH2),C02Hlties up the second phosphoryl group and considerably decreases the Phosphonic and phosphinic acids behave as monobasic acids in acetone and have a much wider spread of PKa values (5-13) than they do in water (2-8).320 The structure and binding properties of nucleoside phosphates have been investigated by a PKa Thermographic measurements have been used to establish the temperature at which reactions start and also to explore the change in reactivities for a series of related reactions, either by modification of the structure of a reactant or by altering the medi~m.3~2

slo

aal ala

V. P. Kukhar’, I. N. Zhmurova, and R. I. Yurchenko, J, Gen. Chem. (U.S.S.R.), 1972, 42, 268. 0. Vikane and J. Songstad, Acta Chem. Scand., 1973, 27,421. T. A. Mastryukova, I. M. Aladzheva, E. I. Matrosov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 1461. E. I. Matrosov, K. Z. Kulumbetova, L. I. Arkhipova, T. Y. Medved, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R., 1972, 21, 193. V. P. Barabanov, V. M. Tsentovskii, A. Ya. Tret’yakova, D. Sh. Zagidullina, F. M. Kharrasova, E. A. Erre, and G. 1. Rakhimova, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2425. C. M. Freyand J. E. Stuehr, J. Amer. Chem. Soc., 1972,94, 8898. A. N. Pudovik, G. V. Dmitrieva, N. P. Anoshina, T. A. Zyablikova, and V. K. Khairullin, Bull. Acad. Sci., U.S.S.R., 1972, 21, 1109; A. V. Fuzhenkova, A. F. Zinkovskii, and B. A. Arbuzov, J. Gen. Chem. (U.S.S.R.),1972,42,490; A. N. Pudovik and N. G. Khusainova, ibid., p. 2159; T. Kh. Gazizov, A. P. Pashinkin, G. V. Drnitrieva, L. L. Tuzova, V. K. Khairullin, and A. N. Pudovik, ibid., p. 1718; A. N. Pudovik, I. V. Konovalova, and V. P. Kakurina, ibid., p. 323.

289

Physical Methods

Molal voiumes and heat capacities of tetraphenylphosphonium chloride have been measured in water and R

I

(244)

!’,*i PO3*-

Ac

CMe-PO,

/ OCMe \

PO,*-

(245)

11 Surface Properties Sugar phosphates 3 2 4 and aminoalkylphosphonates 25 have been analysed by g.1.c.-mass spectrometric methods. Isomeric bis(dimethy1amino)phosphazenes have been separated by g . l . ~and . ~ phosphate ~~ can be estimated by g.1.c. after silylation.327 Dry column chromatography, with its improved efficiency and saving of time and solvent, has been used to isolate phosphono-lipids328and radiolabelled phosphate polymers.s29 Suitable eluant solvent systems have been established for the t.1.c. separation of phosphites, phosphorothioites, and phosphoramidites using A more detailed study of the relation between the structure of phosphates and the t.1.c. behaviour has also been completed.331The sequential hydrolysis of the chain polyester (245) by two-dimensional t.1.c. showed dramatically the degree of polymerization; six spots were obtained from (245 ;n = 5), five spots from (245; n = 4), etc.332The reactions of phosphates and thiophosphate esters with chlorophosphate esters to give pyrophosphates were followed by t.1.c. The plates were developed by 5 % aqueous silver nitrate followed by 2 % Bromothymol R ~ g a r , phosphatide ~~* lipids,33Sand c-GMP 336 have been separated or estimated by t.1.c. Polyphosphates have been studied by ion exchange chromatography337 and by gel c h r ~ m a t o g r a p h y . ~ ~ ~ 818

8z5

888

8a7 828

3zB 880

881

884

886

C. Jolicoeur, P. R. Philip, G. Perron, P. A. Leduc, and J. E. Desnoyers, Canad. J. Chem., 1972,50,3167. D. J. Harvey and M. G. Horning, J. Chromatog., 1973, 76, 51. D. J. Harvey and M. G. Horning, J. Chromatog., 1973, 79, 6 5 ; T. Matsubara and A. Hayashi, Biochim. Biophys. Acta, 1973, 296, 171. J. M. E. Goldschmidt and M. Segev, Inorg. Nuclear Chem. Letters, 1973,9, 163. P. M. Wiese and R. H. Hanson, Analyt. Chem., 1972, 44,2393. C. V. Viswanathan and A. Nagabhushanam, J. Chromatog., 1973, 75,227. W. B. Burton and T. F. Sullivan, J. Agric. Food Chem., 1972, 20, 1180. N. L. Ivanova, A. I. Zavalishina, I. V. Fursenko, I. S. Nasonovskii, I. P. Konyaeva, I. V. Komlev, and E. E. Nifant’ev, J. Gen. Chem. (U.S.S.R.), 1972, 42, 86. A. Lamotte and M. Viricel, J. Chromatog., 1973, 76, 381. J. B. Prentice, 0. T. Quimby, R. J. Grabenstetter, and D. A. Nicholson, J. Amer. Chem. SOC.,1972,94,6119 A. Zwierzak, Phosphorus, 1972, 2, 19. T. I. Golubev and V. A. Volkova, Gigieria i Sanit., 1971, 36, 69. S. R. Eder, Fette, Seifen, Anstrichmittel, 1972, 14, 519. S. Hynie, J. Chromatog., 1973, 76, 270. C. Benz, Analusis, 1973, 2, 56. N. Yoza, M. Tokuda, T. Inoue, and S. Ohashi, Znorg. Nuclear Chem. Letters, 1973,9, 385.

Author Index

Aarons, L. J., 52, 277 Abbas, K., 130 Abdo, W. M., 93 Abduvakhabov, A. A., 252 Abiko, Y., 159 Abola, J., 280 Abramovitch, R. A., 244, 246 Absar, I., 52 Adam, W., 12,240 Adams, D. M., 219, 273 Adams, P., 214 Addison, J. F., 133 Addison, K. S., 219 Adlkofer, J., 172 Agarwal, K. L., 113, 141, 152, 153, 157 Agranat, I;, 191 Aguiar, A. M., 16, 137, 237, 252, 264, 269, 284 Ahmed, F. R., 227, 280 Ahrens. U.. 5 5 . 111. 128 Akagi, ’M.,‘243 Akamsin, V. D., 274 Akiba, K., 243 Akiyama, S., 177, 193 Akramov, S. T., 278 Aksenov, V. I., 285 Aksnes, G., 15, 174, 271 Aladzheva, I. M., 18, 83, 288 Alajeva, I. M., 271 Alberts, A. H., 193 Albrand, J. P., 14, 250, 255,266,267 Alderfer, J. L., 156 Aleksandrov, G. G., 279 Alexander, R. G., 286 Al’fonsov, V. A., 97 Alfredsson, G., 12 Alhadeff, J. A., 160 Allan, R. D., 242 Allcock, H. R., 51, 200, 225, 227 Aliett, D. W., 81, 174, 212,

Allison; W. S.; 161’ Almasi, L., 129, 134, 283 Alric, A. M., 274 Al-Sulimany, F., 284 Anashkin, M. G., 282 Andermann, G., 277 Anderson, A. G., jun., 171 Anderson, D. W. W., 53, 262

Anderson, W. G., 258 Andose, J. D., 13 Andrews, G. C., 110, 242 Andrianov, K. A., 225 Aneja, R., 10, 69 Anisuzzaman, A. K. M., 144 Anoshina, N. P., 57, 93, 198, 288 Ansari, S., 270 Antonyuk, A. S., 188 Appel, R., 10, 67, 103, 186, 205, 21 1 Aranas’eva, D. N., 264 Arbuzov, B. A., 44, 86,92, 93,.253, 260, 281, 288 Archibald, A. R., 164 Arkhipova, L. I., 288 Arnold, D. E. J., 54, 60, 282 Asai, Y., 117 Ashani, Y., 167 Ashe, A. J., 30, 277 Astell, C. R., 141 Atherton, F. R., 243 Auterhoff, G., 194 Awerbouch, O., 32, 268 Ayad, S. R., 141 Baalmann, H. H., 208 Baardman, F., 7 Babkina, E. I., 60 Babsulene, M., 197 Babyak, A. G., 210 Bacci, M., 273 Baccolini, G., 223 Bach, M., 287 Bach, M. C., 281 Bachner, L., 155 Baechler, R. D., 13 Baehler, B., 192 Bahr, W., 155 Baer, E., 160 Baggett, N., 192 Bagrii, E. I., 286 Bagrov, F. V., 40 Bagrov, G. N., 225 Baier, H., 80, 265 Baker, A. D., 277 Bald, R. W., 142 Baldwin, J. E., 101, 240 Banister, A. J., 13 Bankovskaya, N. N., 250 Banyasz, J. L., 138 Barabanov, V. P., 288 Baranov, S. N., 86, 182 Barclay, R., 225 Barker, R. W., 149 Barley, G. C., 191

290

Barnes, F. J., 167 Barrans, J., 47, 48, 268 Barrio, J. R., 145 Barsukov, L. I., 164 Bartell, L. S., 35, 61, 282 Barthelat, M., 268 Barton, D. H., 242 Baschang, G., 98, 105, 143, 144, 202 Basi, J. S., 59 Basu, H., 160 Batich, C., 30, 277 Batyeva, E. S., 93, 97, 198, 207 Baudler, M., 1, 2, 3, 14, 59, 76 Bauer, E., 21, 198 Bauer, G., 198 Bauer, H. J., 42 Bauer, R. J., 142, 144 Baum, A. A., 177 Bazhulina, N. P., 276 Bebazaa, M. H., 17 Bechara, E. J. H., 162 Beck, P., 15 Becke-Goehring, M., 207 Becker, H. J., 3 Beckers, J. L., 157 Beckwith, A. L. J., 139,235 Beeby, P. J., 192 Beer, H., 17, 78 Begum, A., 270 Behrens, N. H., 157 Behrman, E. J., 163 Beinfest, S., 214 Beketov, V. P., 255 Bell, B., 13 Bellet, E. M., 122 Bel’skii, V. E., 251 Belyaev, A. N., 184 Belyaev, N. N., 184 Benary, E., 8, 73, 254 Bender, M. L., 130 Bender, R., 255 Benesch, R., 167, 169 Benesch, R. E., 167, 169 Benezra, C., 135, 263, 265 Benitez, L. V., 161 Benkovic, P. A., 119, 165 Benkovic, S. J., 118, 119, 165 Bennoson, M., 277 Benschop, H. P., 134 Bensoam, J., 62 Bentham, J. E., 53, 54 Bentlev. R. K.. 188 Bentride, W. G., 106, 233, 234, 235 Bentz, F., 86

Author Index Benz, C., 289 Berchtold, G. A., 239 Berge, A., 84 Bergelson, L. D., 164 Bergesen, K., 84, 140 Berglund, O., 149 Bergmann, E. D., 191 Berlin, K. D., 6, 14, 73, 139, 260,286 Berman, S. T., 173 Bermann, M., 200, 204, 217 Bernard, D., 40, 51, 255 Berndt,.J., 153 Bernstem, P. A., 115 Berry, J. P., 84, 127, 160 Bershas, J. P., 24, 187 Bertrand, R. D.. 262 Bertz, S.-H., 181 Beslier, L., 258 Bessell, E. M., 163 Bestmann, H. J., 172, 239 Betteridge, D., 277 Bevtia. E.. 167 Bhkca, N. S., 254 Bhanot, 0. S., 153 Bickel, H., 188, 190 Bickelhaupt, F., 27 Biehler, B., 222 Bigley, D. B., 286 Bilofsky, H. S., 256, 258 Binder, H., 123, 218 Binh, S. K., 170, 284 Birum, G. H., 84 Biryukov, I. P., 268 Birukov, P., 53 Bissell, E. C., 51, 227 Bitter, W., 202 Blackburn, G. M., 157 Blackburn, P., 157 Blaine, L. I., 13 Blanchard, C., 272 Blessing, R. H., 139 Bloxham, D. P., 150 Bochkarev, V. N., 285 Bocian, N., 169 Bock, M., 2 Bodalski, R., 87 Boden, G., 215 Bodesheim, F., 86 Bodkin, C. L., 85, 121 Bodnarchuk, N. D., 210 Boehme, H., 18, 194 Boekelheide. V.. 242 Boenig, I. A., 202 Boersma, J., 3 Bogdanovit, B., 181, 265 Bohlmann, F., 190 Bohn, B., 175 Boie. I.. 133 Boiko, A. P., 210 Boisdon, M.-T., 47 Bokanov, A. I., 82,249,287 Boldeskal, 1. E., 272 Bollum, F. J., 151, 155 Bolotina, N. A., 128 Bond, A., 40 Bonnard, H., 73 Bonvicini, P., 278 Borisenko, A. A., 86 Borisov, G., 103

29 1 Borleske, S. G., 30, 248, 262 Borowitz, G. B., 13 Borowitz, I. J., 13, 140 Bottin-Strzalko, T., 266 Boudreaux, G. J., 21 Boulos, L. S., 42 Boulton, A. J., 240 Bouquant, J., 268 Bowden, F. L., 105 Bradford, H. R., 140 Bradley, E. B., 202 Bragin, J., 258 Bramblett, J. D., 40, 253 Brass, H. J., 130 Braun, M., 4, 56, 70, 271 Braun. R. W.. 35. 62. 257 Brazier, J. F.; 35, 45, 46, 258,278 Breazeale, R. D., 171 Breen, J. J., 15, 248 Brel, A. K., 65 Brentnall, H. J., 156 Bretthauer. R. K.. 164 Briles, G. H., 79 ' Britton, H. G., 165 Brodelius, P., 149 Broline, B. M., 122 Brooke, P. K., 245 Brooks, R. J., 132, 241 Broom, A. D., 155 Brown, C., 116 Brown, F. R., 270 Brown, J. M., 24, 175 Brown, J. N., 21, 279 Bruckmann, R. H., 166 Brun, C., 283 Brun, G., 272 Brunelle, D. J., 194 Bryson, J. G., 30, 261 Buchner, W., 37, 62, 172 Buddrus, J., 170 Budowsky, E. I., 156 Buchi, H., 141, 152 Buerger, H., 270 Bugerenko, E. F., 59, 86, 285 Buisson, D., 151 Bullen, G. J., 227, 280 Bullock, J. I., 56 Bundgaard, T., 32, 253, 262 Bunick, G. J., 166 Bunton, C. A., 117, 132, 24 1 Burg, A. B., 5, 59,250 Burgada, R., 40, 45, 51, 105, 255 Burger, K., 37, 46 Burkhardt, T. J., 181 Burmistrova, N. P., 132 Burton, W. B., 289 Bushweller, C. H., 256,258 Butler, L. G., 164, 166 Bykhovskaya, E. G., 59, 96 Bystrov, V. F., 164 Cacchi, S., 223 Cadogan, J. 1. G., 32, 131, 202, 243

Calhoun, H. P., 227 Callot, H. J., 193 Calvo, C., 280 Cameron, T. A., 126 Cameron, T. S., 280 Campbell, I. G. M., 71 Cann, P. F., 70, 92 Capmau, M. L., 70 Caprioli, R. M., 287 Carey, F. A., 195 Carles, J., 49, 239 Carlson, S. C., 178 Carminatti, H., 157 Carpentier, M., 193 Carreira, L. A., 275 Carreras, J., 165 Carrie, R., 133, 193 Carroll, T. X., 61, 277 Carruthers, W., 192 Caruthers, M. H., 141,152 Cary, L. W., 254 Casey, C. P., 181 Cashel, M., 152 Cashion, P. J., 157 Casper, J. M., 273 Cassidy, P. J., 160 Castan, P., 274 Castro, B., 69, 103 Catlin, J. C., 153 Caton, M. P. L., 188 Cavell, R. G., 35, 59, 63, 256, 271. Centofanti, L. F., 53, 55, 257, 263, 273 Chackrabarti, J. K., 120 Chajkin, L. S., 248 Chakladar, J. K., 111 Chalet, J. M., 192 Challand, S. R., 244 Chambers, R. D., 31 Chan, H. T. J., 176 Chan, J. L. W., 84, 131 Chan, S., 258 Chan, T. H., 81 Chandrasekaran, S., 20, 34 Chang, I. C., 275 Chang, L., 151 Chapleur, Y.,69, 103 Chapman, T. M.,112, 155 Charbonnel, Y.,48, 268 Chasle, M. F., 101, 102 Chasle-Pommeret, M. F., 102 Chattha, M. S., 16, 237, 252, 264, 269, 284 Chatzidakis, A., 136 Chauzov, V. A., 140 Chekhun, A. L,,129 Chekunina, L. I., 82, 249, 287 Chen. C. H., 16. 64

Cherkashina, L. P., 276 Cherkasov, R. A., 139,273 Chernyshev, E. A., 59, 86, 285 Cheung, L. D., 279 Cheung, W. Y., 143

Author Index

292 Chevnova, A. V., 276 Chien, Y. H., 145 Chinara, H., 61 Chirkunova, S. K., 65 Chistokletov, V. N., 17, 90, 172 Chittenden, G. J. F., 163 Chiu, N. Y.,166 Chodkiewicz, W., 70 Chong, K. J., 143 Choplin, F., 283 Christen, P., 164 Chuche, J., 268 Chukova, V. M., 223 Cichon, J., 270 . Cilento, G., 162 Cilley, W. A., 132, 261 Claes, P., 241 Clare, P., 217 Clark, D. T., 30, 277 Clark. M. G.. 150 Clark; P. E., 260 Clarke, F. B., 264 Clive, D. L. J., 81 Cloyd, J. C., 4 Cobley, V. T., 30 Cockerill, A. F., 243 Coffinet, D., 177, 178 Cogne, A., 250 Cohen, H., 135, 263,265 Cohn, K., 52,267 Colbeau, A., 164 Collyer, S. G., 117 Colson, J. G., 252 Colvin, E. W., 191, 195 Connick, W. J., jun., 21 Connor, D. T., 180 Contreras, R., 44, 46, 104, 259,278 Cook, A. F., 153 Cook, A. G., 82, 138 Cook, R. D., 130,131 Cook, R. J., 6 Cook, W. J., 225 Cooperman, B. S., 166 Copenhafer, R. A., 237, 269, 284 Corey, E. J., 10, 175, 177 184, 194 Corre, E., 101, 114 Costisella, B., 89 Cotton, F. A., 169 Coulson, A. F. W., 166 Couret, C., 4, 56 Couret, F., 4, 56 Court, A. S., 195 Court, J., 246 Coustures, Y.,279, 283 Cowley, A. H., 35, 60, 62, 257, 258,273 Cox, R. H., 266 Cradock, S., 52, 53, 277 Cram, D. J., 48 Cramer, F., 153, 154 Crasnier, F., 275, 281 Creighton, D. J., 150 Creighton, J. A., 219 Cremer, S. E., 78, 254, 263 Cresson, P., 70, 105 Crouch, R. K., 140 Crowley, J. L., 283

Csizmadia, I. G., 273 Curcj, R., 80,.99, 138, 240 Currie, J. O., jun., 171 Czieslik, G., 67, 20 1, 202 Czysch, W., 39, 208 Daigle, D. J., 6 Dale, A. J., 286 Dalmatova, L. K., 65 Daly, J. J., 279 Damiani, D., 275 Dang, T.-P., 2 Danion, D., 133, 193 Dannenberg, P. V., 149 Dannhardt, G., 76 Darlix, J. L., 155 Das, R. N., 219, 254 Daves, G. D., jun., 160 Davies, A. G., 231, 232, 235, 269, 270 Davies, A. P., 10, 69 Davies, A. R., 55, 105, 285 Davies, M., 8, 271 Davis, D. G., 248 Davis, J. W., 143 Dawson, R. M. C., 165 Day, V. W., 169 Dean, C. R. S., 52 Dearborn, D. G., 160 De’Ath, N. J., 20 De Bruin, K. E., 19, 20, 34 de Graaf, H. G., 27 Deich, A. Ya., 53, 268 De Koning, H., 194 Delac, J., 145 De la Mare, S., 166 De La Matter, D., 280 Delarco, J., 141 del C. Battle, A. M., 149 de Licastro, S. A., 95 De Luca, M., 145 Demay, C., 36, 63 Demir, T., 126 de Moutier Aldao, E. M., 125, 132, 241 Demuth, R., 250, 270 Denney, D. B., 253, 267 Dennis, R. W., 231, 232, 269,270 Denyer, C. V., 81 Derkach, G. I., 83, 204 Derkach, N. Ya., 59 Desbat, B., 61 Deschamps, B., 193 de Silva, S. O., 187 Desmarchelier. J. M... 98., 134 Desmarteau, D. D., 115 Desnoyers, J. E., 289 Desseyn, H. O., 272, 274 Devilliers. J.. 266 Devlin, C: J.; 173, 259 Dewar, M. J. S., 258 De-Wit, J., 68 Dheer, S. K., 153 Dianova, E. N., 86 Dickstein. J. I.. 42 Didych, M.N.;5 5 Diebert, C. E., 130 Dieck, R. L., 218, 219

Diehl, J. W., 12, 240 Dierdorf, D. S., 35, 60 Dietl, M., 134 Di Furia, F., 80, 99, 240 Diggelman, H., 141 Dimmitt, M. K., 143, 144 Dimroth, K., 28, 29, 136, 239 Disteldorf, M. R. W., 135 Disteldorf, W., 79 Dmitrieva, G. V., 57, 288 Doak, G. O., 35,60, 257 Dogadina, A. V., 63, 64, 252, 264, 283 Doggett, G.,.218 Dombrovskii, A. V., 188 Donskaya, Yu. A., 274 Dormidonov, I. A., 129 Douglas, K. T., 120 Drach, B. S., 16 Dreeskamp, H., 172 Dreifus, H., 214 Dreissig, W., 279 Dronsfield, A. T., 55, 105, 285 Druyan, E. A., 278 Dryburgh, J. S., 54 Drysdale, J. W., 157 Dubbeldon, J., 27 Duesler, E. N., 280 Duff, E., 38, 252 Dufourcq, J., 164, 266 Dunnill, P., 159 Dunstan, P. 0. L., 272 Durig, J. R., 273, 275 Durrant, G., 196 Dutton, P. L., 161 Duty, R. C., 66 D’Yakonova, N. I., 57 D’yakoy, V. M., 96 Dyrnesli, R., 121 Eastlick, D. T., 131 Easwaran, C. V., 147 Eaton, M. A. W., 155 Ebeling, J., 215 Ebsworth, E. A. V., 53, 54, 60. 262.277. 282 Ecker, A.; 133; 230 Eckert, H., 213 Eckstein, F., 146, 147, 149, 150. 155 Ecksteini -U., 79, 135 Edelev, M. G., 222 Edel’man, T. G., 213, 276 Eder, H., 192 Eder, S. R., 289 Edmonds, M., 141 Eenkhoorn, J. A., 187 Efimova, E. I., 126 Efremov. U. Y., 285 Egan, W;, 261 . Egorov, Yu. P., 213 Eichelberger, J. L., 76, 230 Eiki. T.. 117 Eiletz, H., 201 Einhellig, K., 46 Eisenhut, M., 35, 63, 281 Eiter, K., 184 Ekrene, J., 272

Author Index Elbein, A. D., 157 Elin, E. S., 89 Elix, J. A., 176 Ellis, K., 20 Ellzey, S. E., jun., 21 El'natanov, Yu. I., 4, 13, 259, 264 El'nikova, G. N., 58 Elphingstone, E. A., 59,75 Emundson, R. S., 140 Engberg, E. A., 225 Engel, J. F., 15, 30, 248, 26 Englm, M. A., 54 Erecinska, M., 161 Eredzhepova, Z. A., 277 Erre, E. A., 288 Eto, M., 112 Evans, D. A., 110,242 Evdakov, V. P., 255 Evdokimov, V. V., 281 Evdokimova, N. V., 64 Evelyn, L., 265 Everaerts, F. M., 157 Evstaf'ev, G. I., 252 Exner, O., 283 Faerber, P., 155 Fahmy, M. A. H., 123 Falbriard, J. G., 150 Fales. H. M.. 160 Falius, H., 55, 111, 128, 26 1 Faller, J. W., 268 Fallis, A. G., 187 Fang, K. N., 154 Farley, I. R. T., 166 Fatkullina. F. A.. 277 Faust, C. H., jun:, 141 Favero, P. G., 275 Fazliev, D. F., 273 Featherman, S. I., 255 Fedechkina, V. A., 92 Fedin, E. I., 254, 259 Fedor, J., 119 Fehn, J., 37, 46 Feldman, F., 164 Fenske, D., 3 Ferdinand, W., 157 Ferekh, J., 35 Ferguson, B. A., 176 Fernando, W. S., 219, 273 Feshchenko, N. G., 58, 59 Fey, G. T. K., 52, 270 Field, K. B., 13 Fierman, A. H., 130 Filatov, A. S., 54 Filippov, E. A., 207, 223 Filippovich, Yu. B., 264 Filonenko, L. P., 206 Finch, A., 52 Finkelhor, R. S., 180 Finkenbine, J. R., 81 Finnegan, R. A., 123,228 Firestone, R. A., 161 Fischer, D. E., 26,237,286 Fischer, G. W., 125 Fischer, R., 123 Fitseva, R. G., 132 Flaskerud, G., 202

293 Flatau, G. N., 36, 63 Fleming, S., 55, 248 FliszAr, S., 49, 239 Flitsch, W., 178 Fluck, E., 205, 207, 247 Fliigel, R. M., 155 Flygare, W. H., 275 Foester, R., 267 Fomichev, A. A., 4, 259 Fomin, A. A., 222 Formoso, C., 278 Forostyan, Y. N., 126 Foroughi, K., 51, 111 Forsee, W. T., 157 Forsen, S., 261 Forti, P., 275 Foster, C. H., 239 Foster, S. A., 98, 246 Foucaud, A., 101, 102,114 Fox, J. J., 188 Francis, G. W., 191 Frank, A. W., 111 Frank, V. S., 225 Franke, R., 172 Fraser, M., 30 Frazier. S. E.. 18

Frisch, H: U..-143 Frischauf, A.; 149 Froede, H. C., 116 Frsyen, P., 174, 198, 286 Frohlich, A., 65 Frolov, Yu. L., 270 Fromageot, P., 155 Frye, H., 2 Fu, J.-J. L., 234, 235 Fuchs, P. L., 9, 10, 38, 81, 177

Fuinitto, R., 264 Fugol, V. A., 225 Fujii, S., 243 Fujimoto, T. T., 110, 242 Fujiyama, F., 11, 110, 197 Fukiya, A., 225 Fukui, S., 158 Fukui, T., 155 Fukuto, T. R., 98,122,123, 134 Furimsky, E., 235 Fursenko, I. V., 289 Furtsch, T. A., 35, 60 Fuzhenkova, A. V., 86,92, 93, 288 Fyfe, C. A., 7 Gabbai, A., 150 Gachegov, Yu. N., 37, 269 Gagnaire, D., 14, 140, 237, 250, 255, 267 Gaidamaka, S. N., 37, 209, 269,271 Gal, J. Y., 122 Galeev, V. S., 64, 276 Galishev, V. A., 90 Galivan, J., 142

Gamaleya, V. F., 124 Gareev, R. D., 82, 252, 256, 265, 274, 283 Garegg, P. J., 12 Garratt, P. J., 191 Garwood, D. C., 48 Gassen, H. G., 155 Gates, B. J., 145 Gates, P. N., 52 Gay, D. C., 118 Gaydon, E. M., 97,98,267 Gazit, A., 183 Gazizov, M. B., 58 Gazizov, T. Kh., 57, 288 Gee, R., 32, 202 Geraghty, M. B., 191 Gerchman, L. L., 155 Germa, H., 105 Ghirardelli, R. G., 197 Ghouse, K. M., 280 Gieren, A., 46 Gilbert, B. C., 235 Gilgen, P., 175 Gilham, P. T., 146, 156, 157 Gillespie, P., 34, 98, 115, 117 Gilman, A. G., 145 Gilmore, W. F., 89, 128, 136, 194 Gilyarov, V. A., 114, 204 Gilyazov, M. M., 73 Girijavallabhan, M., 242 Glamowski, E. J., 161 Glaser, S., 117 Glemser, O., 67, 201, 202, 21 9

Glidewell, C., 52, 281 Glindemann, D., 213,237 Glinka. K.. 1 Gloede, J.,'86 Glover, W., 13 Godovikov, N. N., 252 Goetz, H., 282 Goetze, R., 101 Goldberg, N. D., 143 Goldberg, S. Z., 280 Gol'dfarb, E. I., 57, 104, 235, 266,269 Golding, B. T., 175 Goldschmidt, J. M. E., 200, 220,289 Goldschmidt, S., 55 Goldwhite, H., 258 Golik, G. A., 127, 268 Golubev, T. I., 289 Goodchild, J., 153 Goody, R. S., 150 Gorbatenko, V. I., 272 Gorbatenko, Zh. K., 58 Gordeev, A. D., 37, 127, 268, 269 Gosling, K., 54, 271 Gosteli, J., 190 Goubeau, J., 82, 274 Grabenstetter, R. J., 97, 289 Grachev, M. A., 156 Gracy, R. W., 166 Graham, J. C., 222 Gramstad, T., 272

Author Index Granoth, I., 285 Grapov, A. F., 83, 132 Gray, G. A., 78, 254, 263 Grechkin, E. F., 61 Green, B., 217, 220, 277 Green, E. E., 73 Green, M., 40 Greenberg, J. R., 141 Greenhalgh, R., 15 Greenwald. J.. 123. 276 180,’ 195 Grieco, P. A.,‘ Griffin, C. E., 235 Griller, D., 232, 233, 235, 269. 270 Grimm, L. F., 127 Grisolia, S., 165 Grobe, J., 250, 270 Grohmann, K., 191 Groman, E., 158 Grosfeld, H., 157 Gross, B., 69, 103 Gross, H., 89 Gruk, M. P., 44 Gubnitskaya, E. S., 124, 204 Gudkova, I. P., 163 Guenter, N., 86 Giinther, H., 135 Gueron, M., 261 Guessenhainer, S., 154 Guest, M. F., 52, 277 Guilford, H., 149 Guillemonat, A., 98 Guillerm, D., 70 Guillou, Y., 169 Gulyaeva, N. A., 281 Gupta, N. K., 141, 152 Gurarii, L. I., 285 Guroff, G., 141 Gurudata, N., 135, 263 Gurylev, E. A., 53, 268 Gusakova, G. S., 96 Gusev, A. I., 279 Gushlbauer, W., 261 Gutteridge, M. J. A., 243

Hansen, E. R., 234 Hansen, H.-J., 177 Hansen, R. S., 263 Hanson, R. H., 289 Hantz, A., 129 Hardman, J. G., 143 Harland, P. W., 285 Harper, P. J., 148 Harris, R. J., 141 Harris, R. K., 39, 67, 82, 129, 257, 259, 261 Harrison, W., 227 Hartford, S. L., 275 Hartman, F. C., 166 Hartmann, A., 135 Harvey, C. L., 153 Harvey, D. J., 289 Hase, H. L., 32, 253 Hassairi, M., 102 Haszeldine, R. N., 55, 105, 285 Hata, T., 114, 143, 153 Hattori, M., 155 Haubold, W., 207 Haugen, H., 15, 271 Hauptmann, H., 33 Hayashi, A., 165, 289 Hazama, M., 265 Hazen, E. E., jun., 169 Healy, H. J., 164 Hearn, M. T. W., 187 Hecht, S. M., 280 Heep, U., 138, 196 Heidelberger, C., 149 Heier, K.-H., 27 Heilbronner, E., 30, 277 Heinrickson, R. L., 166 Heitz, W., 170 Heller, W., 1 Hellwinkel. D.. 19. 40.

H erbert; R. B., 245 H erbes, W. F., 5 H ercules, D. M., 213 H erman, M. A., 272, 274 H eron, E. J., 287 H ershberg, R., 43, 253 H ettche, A., 29, 239 H eusler, K., 188 H ewson, M. J. C., 36, 281 H eyde, E., 165 H eydenreich, F., 172 H igashi, F., 109 H igashiyama, T., 120, 151 H iggins, J., 76, 230 H ilgetag, G., 18 H 111, R. L., 149 H illier, I. H., 52, 277 H jortas, J., 279 H 0,N. W. Y., 156 H 0,T.-L., 68 H obbs, J., 155 H[odges, H. L., 53, 262 H[oefler, F., 270 H ofer, R., 202 H offmann, E. G., 172

Hoffmann, R., 34, 44, 61, 257 Hoffsommer, R. D., 176 Hogenkamp, H. P. C., 149 Holah, D. G., 30 Holland, J. M., 276 Holland, P. C., 150 Holliman, F. G., 245 Holmes, R. R., 52, 270 Holf, A., 141, 142, 143 Homer, G. D., 15 Hong, N. D., 143 HOOS,W , R., 51 Horiguchi, M., 160 Horn, H. G., 250 Horn, T., 159 Horning, M. G., 289 Hornung, V., 30, 277 Horten, H. L., 106 Horwitz, J. P., 147 Hosokawa, T., 159 Houalla, D., 45, 47, 104, 258, 268 Howard, J. A., 235 Howatson, J. H., 61 Howell, J. M., 44, 61 Howells, D., 70, 71 Howes, P. D., 191 Howlett, K. D., 126, 280 Hrdina, P. D., 268 Hruska, F. E., 248, 266 Hsu, C. S., 275 Huang, Y. Z., 158 Huber, J. W., tert., 136, 194 Huche, M., 70, 105 Hudson, H. R., 85 Hudson, R. F., 15, 91, 116 Huestis, W. H., 167, 248 Hug, R., 177 H;@es, A. N., 8, 30, 77,

~

H aake, M., 18, 194 H aake, P., 130 H aar, W., 146 H adden, E. M., 143 H adden, J. W., 143 H addox, M. K., 143 H artel, M., 193 H agele, G., 82, 261 H agen, A. P., 59, 75 H agnauer, G. L., 225 H ahn, H., 32, 253 H aley, B., 150 H all, C. D., 40, 253 H all, L. D., 265 H all, M. B., 52, 277 H almann, M., 123, 276 H amashima, Y., 169 H amer, N. K., I 1 8 H amill, B. J., 195 H[amilton, L. A , 111 H[amilton, W. C., 181, 280 H[ampton, A., 148 Hlands, C. H. G., 215 H[andschuh, (3.J., 148

Hutchins; R. 0.; 24, 248, 250

Hutchinson, D. W., 155, 156 Hutley, B. G., 174 Hynie, S., 289 Ignatova, N. P., 248 Iio, M., 112 Ikeda, S. I., 158 Ikehara, M., 148, 154, 155 Ikeno, S., 223 Il’yasov, A. V., 235, 269 Imoto, M., 128 Inamoto, N., 199, 243 Inch, T. D., 121, 140 Inesi. G., 248 Ingold, K. U., 233, 234, 269. 270 Inokawa, S., 111 Inoue, T., 289

Author Index Inoyatova, K., 252 Ionescu, L. G., 117 Ionin, B. I., 63, 64, 128, 252, 254, 264, 283

Ireland, R. E., 122 Isaacs, N. S., 10, 68 Isbell, A. F., 84, 127, 160 Ishi, Y., 172 Ishikawa, K., 65 Ishmaeva, E. A., 82, 283 Issleib, K., 2, 9, 261 Itoh, K., 172 Itskova, A. L., 284 Ivanov, B. E., 71, 86, 251 Ivanova, N. L., 289 Iwata, K.-I., 113, 229 Iwata, T., 169 Izawa, Y.,136, 228, 286 Izydore, R. A., 197

295 Karayannis, N. M., 272 Karlstedt, N. B., 9, 286 Karpeiskii, M. Ya., 276 Kasai, Y., 125 Kashman, Y., 8, 32, 73, 254,268

Kaska, W. C., 178 Kato, S., 172 Kato, T., 172 Katz, T. J., 24, 39, 252, 256

Katzman, S. M., 240 Kauffmann, J., 237 Kauffmann, T., 2 13 Kaufmann, C., 157 Kaufmann, G., 283 Kawamoto, I., 183, 266 Kawamura, H., 223 Kazantseu, A. V., 1 Keat, R., 126, 208, 267, 268, 280

Jackson, W. R., 258 Jacobus, J., 261 Jacura, Z., 214 Jafkowski, M., 18 Jafry, S. W. S., 8, 271 Jakobsen, H. J., 32, 253, 262,263

Janzen, A. F., 9 Jarvis, B. B., 12 Jastorff, B., 144 Jatkowskii, M., 127 Jay, E., 113, 153, 157 Jeanloz, R. W., 157 Jeck, R., 159 Jekot, K., 55, 248 Jennings, W. B., 258 Jerkunico, I., 142 Jessep, H. F., 60, 282 Joesten, M. D., 255 Johnson, A. W., 212 Johnson, K. H., 169 Jolicoeur, C., 289 Jonas, J.; 253 Jones, D. W., 276 Jones, E. R. H., 187, 188, 191

Jones, M. R., 48 Josey, A. D., 211 Jourdan, G., 272 Juds, H., 282

Keenan, R. W., 150 Kelsch, U., 1 Kemp, N. R., 277 Kemp, P., 165 Kennard. 0.. 191 Kenyon, G . L., 72, 116, I

,

-

150, 263

Kerek, F., 264 Kerr, C. M. L., 270 Keschmann, E., 24 Kezele, B. A., 283 Khaikin, L. S., 282 Khairullin, R. K., 83 Khairullin, V. K., 57, 138, 288

Khairutdinova, F. K., 139, 273

Khafaturnik, M. V., 188 Khalil, F. Y., 174 Khalitov. F. G . . 274 Khan, A:, 155 ' Khan, W. A., 234 Khananashvili, L. M., 225 Khare, G . P., 142 Kharrasova, F. M., 288 Khatoon, N., 191 Khayarov, A. I., 266 Khomenko, D. P., 213 Khorana, H. G., 113, 141, 152, 153, 157

Khurshid, M., 155 Khusainova, N. G., 138, 288

Kabachnik, M. I., 18, 25,

73. 82. 114. 204. 225. 252, 254, 259, 272, 275; 287, 288 Kaczorowski, G . J., 164 Kagan, H. B., 2 Kahan. F. M.. 160 Kajiwara, M.,'222, 225 Kajtar, M., 278 Kakurina, V. P., 288 Kalinin, A. V., 188 Kamaev, F., 252 Kamai, G . Kh., 55, 82, 128 Kanamato, N., 119, 120 Kang, D. K., 250 Kanter, H., 29

Khwaja, T. A., 143 Kibardina, L. K., 266 Kido. F.. 191

Kinnier,' W., 145 Kinoshita, M., 128 Kireev, V. V., 207, 221, 222, 223

Kirkbright, G . F., 278 Kirkegaard L. H., 145 Kirkpatrick, D., 10, 68 Kirpichnikov, P. A., 231

Kirsanov, A. V., 14, 16,

59, 66, 75, 84, 210, 212, 213, 272, 276 Kishida, Y., 183, 266 Kittredge, J. S., 160 Kjeldgaard, N. O., 152 Klabuhn, B., 282 Klaebe, A., 46, 258, 278 Klapper, H., 21 Kleid, D. G., 112, 155 Klein, H. A., 52, 66, 200 Klein, R. A., 165, 287 Klein, R. S . , 188 Kleinstiick, R., 186, 205 Kleppe, K., 141, 152 Klosowski, J., 219 Kluba, M., 110, 264 Kluger, R., 84, 131 Knachel, H. C., 61 Knaggs, J. A., 10, 69 Knoll, F., 67, 211 Knowles, J. R., 166 Knunyants, I. L., 59, 96 KO, E. C . F., 116 Kobatake, H., 243 Kobayashi, E., 219 Kobayashi, M., 154 Kober, E. H., 225 Koch, K., 1 Kochetkov, N. K., 145 Kochi, J. K., 231, 269 Koenig, M., 104 Koerner, T. A. W., 254 Kossel, H., 157 Koster, H., 154 Kole, R., 147 Kolesnikov, S. A., 225 Kolodny, R., 4 Komlev, I. V., 289 Komori, S., 66 Kondo, K., 194 Kondratenko, V. I., 127 Konieczny, M., 122 Kononenko, I. M., 59 Konotopova, S. P., 172 Konovalova, I. V., 86, 132, 288 Konstantinovik, S., 181, 265 Konyaeva, I. P., 289 Kool. J. P. V.. 73 Koos, E. W., 73 Kopecky, K. R., 238 Korn, E. D., 160 Korolev, B. A., 114 Korshak, V. V., 207, 221, 222, 223 Korytnyk, W., 158 Kosinskaya, I. M., 209 Kosovtsev, V. V., 90 Kost, A. A., 145 Kostyanovskii, R. G., 4, 13,259, 264 Koszmehl, G., 175 Kotokuma, K., 223 Kovaleva, T. V., 58, 59 Kovtun, V. Yu., 204 Koyama, T., 167 Kozlov, E. S., 14, 37, 75, 209, 269, 271 Kozlov, N. S., 89

296 Kozlova, N. Y., 120 Kozlova, T. F., 83 Krasil’nikova, E. A., 250 Kraus, M. A., 191 Krauss, H.-L., 5 5 Krebs, T., 144 Kricheldorf, H. R., 199, 27 1 Krivun, S. V., 86, 182 Kruglik, L. I., 272 Kruglyak, Y. L., 103 Krusic, P. J., 231, 269 Krut-skii, L. N., 250 KiicerovB, Z., 142 Kuchen, W., 1 Kucherova, M. N., 201,210 Kudo, M., 192 Kudryavtseva, L. A., 251 Kugler, H. J., 42, 253 Kukar’, V. P., 84,210,213, 276, 288 Kukhta, E. P., 126 Kulumbetova, K. Z., 288 Kumar, A., 141, 152 Kunzek, H., 4, 56, 70,271 Kuo, C. H., 176 Kuramchin, I. Y., 271 Kurihara, T., 243 Kustan, E. H., 13, 241 Kvita, V., 98, 105, 143,144, 202 Kyba, E. P., 246 Kyrtopoulos, S. A., 158 Kyuntsel, I. A., 127, 268 Laakso, P. V., 115 LaBar, R. A., 171 Labarre, J. F., 275, 281 Labarre, M. C., 274, 279, 283 Labaw, C. S., 22, 186 L’AbbC, G., 180, 204 Lake, W. C., 144 La Mar, G. N., 268 Lambert, R. W., 243 Lamed, R., 149 Lamotte, A., 289 Lampin, J.-P., 79, 137, 268 Landis, J., 169 Landis, P. S., 111 Lam. F., 178 Langenbach, R. J., 149 Langer, E., 3 Lard, E. W., 225 Lardy, H. A., 150 Larkin. J. P.. 235 Larkin; R. H., 52, 270 Larsen, S., 106, 169 Larsson, P. Q., 149 Laskorin, B. N., 274 Laszkiewicz, B., 225 Latscha, H. P., 52, 66, 200 Lauppe, H. F., 159 Laurenco, C., 40, 45, 51, ?CC L-JJ

Lavielle, G., 193 Lawesson, S.-O., 121 Lazareva. M. V.. 8 7 Leary, R: D., 35, 63, 256, 271

Author Index Lebedev, V. M., 225 Le Blanc, R., 101, 114 Le Corre, M., 178 Lederle, H. F., 225 Leduc, M., 102 Leduc, P. A., 289 Lee, P. L., 52 Lefebvre, G., 193 Lehmann, H. A., 215 Lehmann, K. A., 237 Le-Hong, N., 192 Leibovici, C., 275, 281 Leloir, L. F., 157, 163 Lennarz, W. J., 157, 164 Leonard, F., 13 Leonard, N. J., 145 Leont’ev, V. B., 252 Lequan, R. M., 253 Lerach, H., 145 Lever, 0. W., 101, 240 Levi, A., 138, 278 Levin, Y., 149 Levin, Ya. A., 64, 71, 73, 86, 235, 269, 276 Levy, J. B., 285 Lewis, G. J., 121, 140 Leyshon, L1. J., 98, 246 Lezius, A. G., 155 Li, P. K., 133 Li, Y. S., 275 Liedke, P., 277 Lilly, M. D., 159 Lin, F. F. S., 40, 253 Lin, T. P., 219 Lincoln, D. N., 261 Lindberg, U., 141 Lindner, E., 17, 78 Lindner, R., 261 Lindsay, J. G., 161 Lines, E. L., 53, 5 5 , 257 Ling, G. M., 268 Liorber, B. I., 251 Lipatova, I. P., 139, 273 Lipmann, F., 152 Lischewski, M., 2 Littauer, U. Z., 157 Littlefield, L. B., 35, 60, 257 Lobanov, D. I., 82, 272, 287 Loeber, D. E., 191 Lomakin, A. Ya., 276 Lopez, L., 47, 268 Lo_p_u_sinSki,A., 108, 115, LUL

Lucchini, V., 138 Lucken, E. A. C., 258 Luckenbach, R., 13, 18 Ludlum. D. B.. 155 Luezak,‘J., 259’ Lukin, A. M., 128 Lunasin, A., 145 Lund, E., 152 Lupton, M. K., 5 5 , 248 Lussan, C., 164, 266 Lustig, E., 261 Lutsenko, I. F., 9, 84, 129, 140, 286 Lynch, D. M., 15 Lyons, A. R., 82, 236, 269 Lyons, G., 66

McBride, H. A., 89, 128 McClure, D. E., 37, 101, 238 McComas, W., 13 McCullough, J. J., 280 McDonald, J. J., 145 McElroy, W. D., 145 McEwen, W. E., 20, 79 McFarlane, H. C. E., 254 McFarlane, W., 254, 262, 264, 266 McGandy, E. L., 139 McGirk, R. H., 192 McGuinness, E. T., 143 Mach, B., 141 McHenry, C. S., 166 Mack, D. P., 225 McKenna, G. P., 166 Maclagan, R. G. A. R., 60 McMurry, T. B. H., 65 McMurray, W. C., 164 Maeda, N., 169 Maercker, A., 173 Markl, G., 26, 27, 28, 33, 53, 73, 76, 80, 237, 265, 286 Magdeev, I. M., 71, 86 Magee, W. L., 164 Mahler, W., 231, 269 Mahran, M. R., 42, 93 Maichuk, D. T., 153 Maier, L., 1, 77, 84, 86, 128, 138, 261 Majoral, J. P., 138, 267, 273 Makaruk, M. S., 55 Makhamtkhanov, M. M., 287 Makitra, R. G., 55 Maksudov, A. M., 278 Malakhova, I. G., 254 Malekin, S. I., 103 Malevannaya, R. A,, 82, 272 Mali, R. S., 190 Malkievicz, A., 154 Mallo, G. N., 194 Mancuso, A., 91 Mandel’baum, Ya. A., 284 Manecke, G., 193 Mankowski-Favelier, R., 32 Manley, T. R., 219 Mann, F. G., 2, 75, 78, 81, 212, 261, 273 Mannofov, T. G., 273 Manojlovit-Muir, Lj., 181, 280 Marchand, E., 102 Marcus, I., 150 Mareev. Yu. M.. 44. 253. 260 Markovskii, L. N., 66 M t y a r d i n g , D., 34, 98, I

,

I

113

Marr, D. H., 222, 252 Marschner, F., 282 Marsi, K. L., 15, 19 Marsmann, H., 15, 250, 282 Martin, J., 267

I

Author Index Martin, S. F., 173 Martynov, I. V., 103 Martynov, V. F., 129 Martynyuk, A. P., 212,276 Maryanoff, B. E., 75, 248, 250 Mashlyakovskii, L. N., 128 Mason, G. W., 82, 138 MassouliC, J., 155 Mastryukova, T. A., 18, 25, 87, 259, 271, 288 Masuda, H., 113, 229 Masukane, K., 61 Mathey, F., 31, 32, 33, 62, 73, 76, 77, 79, 137, 268 Mathis, F., 46, 258 Mathis, R., 268 Mathur, S. S., 240 Mathys, G., 180 Matrosov, E. I., 18, 25, 82, 271,272,288 Matson, J. A., 123, 228 Matsubara, T., 165, 289 Matsumoto, M., 165 Matsumoto, S., 113, 229 Matsuzawa, K., 225 Matthaei, H., 155 Matthes, D., 28, 53, 73 Maumy, M., 264 Maund, J. K., 215 Maurer, W., 146 Mayo, B. C., 268 Mazhar-ul-Haque, 21 Mazzola, E., 258 Meakin, P., 34, 61, 257, 269

Mebazaa, M. H., 21, 264 Medved, T. Y., 288 Meikle. G. D.. 262 Mel’nichenko.’ I. V.. 120 Mel’nikov, N: N., 83, 132, 169,248, 282 Mendenhall, G. D., 12,238 Mendiara, S., 149 Mercer, A. J. H., 2, 75, 78, 26 1 Mercer, J. F. B., 141 Mergner, R., 13 Mertis, K., 24 Meyer, R. B., jun., 144 Mhala, M. M., 117, 120 Michalski, J., 115, 262, 263 Michels, R., 170 Mikolajczyk, M., 108, 139, 259, 260, 278 Mildvan, A. S., 166 Milewski, C. A., 24 Miller, D. L., 152 Miller, F. A., 270 Miller, J. A., 57, 70, 72, 77 Miller, J. L., 54, 271 Miller, J. P., 143 Millington, D., 221, 227 Mills, H. H., 280 Milner, Y., 165 Min, T. B., 234 Mindlin, Ya. I., 225 Mingaleva, K. S., 63, 283 Mironova, Z. N., 73 Mjshkevich, A. E., 109 Mishra, S. P., 218, 237

297 Mislow, K., 6, 13, 35, 75 Mitchell, D. K., 178 Mitchell, R. H., 191 Mitschke, K.-H., 37, 62 Mitsunobu, O., 113, 229 Miwa, M., 165 Mizuta, M., 172 Modro, T. A., 135 Moe, 0. A., 166 Moedritzer, K., 255 Moeller, T., 218, 219 Moffat, J., 240 Moffatt, J. G., 10, 69, 142 Mokashi, A. M., 5 Mol, A., 161 Mollbach, A., 172 Monahan, A., 191 Monastyrskaya, G. S., 156 Monson, R. S., 121,122 Moreland, C. G., 35, 60, 257 Moretto, H., 54 Morgan, W. E., 139, 213 Morozov, Yu. V., 276 Morris, D. L.,14 Morrison, J. D., 284 Morrison, J. F., 165 Morse, J. G., 282, 283 Mortier, R. M., 225 Mosbach, K., 149 Mosbo, J. A., 106, 108, 140, 260 Moskva, V. V., 252, 259, 264 Moslenaar, M. J., 194 Muchmore, D. C., 122 Mudraya, L. M., 65 Mudryi, F. V., 65 Muetterties, E. L., 34, 44, 61, 257 Mukherjee, D. C., 111 Mukmenev, E. T., 281, 285 Mukmeneva, N. A., 231 Muller, E., 46 Muller, G., 73 Munoz, A., 35, 104 Murakami, Y., 119, 120 Muratova, A. A., 271 Murrav. K.. 156 Murrai; M:, 39, 67, 129, 257,259, 261 Murray, W. P., 22, 186 M:sQer, J. I., 35, 60, 256, LJ I

Myers, D. K., 15, 248 Myers, K., 277 Mynott, R. J., 248, 266 Mysin, R. Z., 285 Nagabhushanam, A., 289 Nagao, Y., 229 Nagasawa, K., 119 Nagase, O., 159 Nagyvary, J., 147 Nakagawa, I., 114, 153 Nakagawa, M., 177, 193 Nakahara, A., 120, 151 Nakamara, K., 225 Nakamura, M., 61

Nakamura, N., 61 Nakanishi, A., 123 Nakazato, H., 141 Narang, S. A., 153 Narasimhan, N. S., 190 Nasonovskii, I. S., 289 Naumov, V. A., 281 Navech, J., 138, 266, 267, 213 Nayler, J. H. C., 190 Naylor, R. A., 117 Nazvanova, G. F., 252, 259, 264 Nechaev, Yu. D., 264 Neff, R. O., 111 Negrebeckij, V. V., 248 Negrebetskii, V. V., 73 Neilson, G. W., 236 Nelson, N., 151 Nesener, E., 4, 56, 70, 271 Nesmeyanov, N. A., 173, 188 Nesterenko, V. D., 93, 198, 207 Neumann, G. M., 219 Newman, M. S., 16, 64 Newton, M. D., 140 Newton, M. G., 266 Nichols, J. M., 82, 261 Nicholson, D. A., 89, 97, 132, 261, 289 Nicolaides, D. N., 191 Niecke, E., 202, 219 Niedenzu, K., 202 Nifant’ev, E. E., 89, 163, 264, 289 Nikolaev, A. V., 73 Nikoronov, K. V., 53, 268 Ninomiya, K., 125 Nishimura, J. S., 150 Nlshino, T., 167 Nishiwaki, T., 11, 110, 197, 286 Noth, H., 55, 101 Nogrady, T., 268 Nohira, H., 2 Noltes, J. G., 3 Norman, J. G., jun., 169 Norman, R. 0. C., 235 Normand, F. L., 6 Norris, C. L., 275 Norrish, H. K., 131 Novak, J. J. K., 150 Novikova, Z. S., 84 Novosel’skaya, A. D., 86 Nowak, T., 166 Nowoswiat, E. F., 153 Noyes, C., 166 Nunn, M. J., 51, 77 Nuretkinov, I. A., 269 Nussbaum, A. L., 153 Nycz, D. M., 21, 186 Oae, S., 123, 240 Oakley, R. T., 218 Oba, M., 225 Oberlander, J. E., 19 O’Connell, E. L., 165, 166 Odom, J. D., 275 Oediger, H., 184

Author Index

298 Oehme, H., 9 Offord, R. E., 166 Oeata. T.. 111 Ogata; Y:, 136, 228, 235, 286 Ohashi, S., 289 Ogawa, H., 191, 192 Ogura, K., 167 Ohloff, G., 190 Ohlsson, R., 149 Ohoka, M., 66 Ohtsuka, E., 141, 152 Okada, E., 243 Okada, T., 14 Okawara, R., 14 Okazaki, M., 194 Okhrimenko, I. S., 128 Okruszek, A., 262 Oleinik, D. M., 286 Olsen, K. W., 149 Omelanczuk, J., 139, 278 O’Neil, J. W., 258 O’Neill, S. R., 55 Oplatka, A., 149 Orgel, L. E., 148 Orlov, N. F., 96 Orlovskii, V. V., 109 Osman, F. H., 42, 93 Osokin, D. J., 269 Ostamina, L. P., 58 Ostrogovich, G., 264 Ottmann, G. F., 225 Ovodkov, A. P., 225 Paddock, N. L., 214, 218, 223, 224, 227 Pak, V. D., 89 Pal, B. B., 111 Pant, B. C., 270 Pantzer, R., 82 Para, M., 139, 278 Parish, J. H., 141 Parker, T., 167, 188 Parodi, A. J., 157 Parrett, F. W., 56 Parry, R. W., 273,282,283 Pashinkin, A. P., 57, 288 Paskucz, L., 283 Pastan, I., 143 Pasternak, V. I., 84 Patchornik, A., 155 Paulsen, H., 95, 163 Pawlak, M., 190 Payne, D. H., 2 Payne, D. S., 101 Pearson, E. F., 275 Pearson, M. J., 190 Pearson, S. C., 40 Pedersen, E. B., 121 Peeters, H., 178 Peiffer, G., 98 Pelissier, M., 275 Pellatt, M. G., 192 Penkovskii, V. V., 213 Penzer, G. R., 268 Pepperman, A. B., 6, 266 Perahia, D., 280 Perekalin, V. V., 87 Perren, E. A., 56 Perret, F., 192

Perron, G., 289 Perry, R. P., 141 Persson, T., 141 Peter, H., 188 Petersen, H., 16, 84 Petersen, J. R., 19 Petersen, O., 48, 67 Peterson, M. B., 280 Petkovic, D. M., 283 Petrenko, A. V., 225 Petro, V. P., 61 Petrosyan, V. S., 188 Petrov, A. A., 17, 40, 44, 63, 64, 89, 90, 128, 172, 184, 252, 264, 283 Petrov, K. A., 65 Petrov, M. L., 89 Petrov, S. M., 277 Petrovskaya, L. I., 73 Petrovskii, P. V., 25, 254, 259, 271 Pettit, G. R., 141 Pettit, W. A., 5 , 130 Petukhova, A. S., 59, 86 Pfuller, H., 239 Phhlaja, K., 267 Philip, P. R., 289 Pickos, A., 135 Piers, E., 191 Pietrusiewicz, K., 87 Piette, L. H., 164 Pilot, J. F., 181, 280 Pilyugin, V. S., 277 Pinchuk, A. M., 206, 209 Pinder, P. M., 52, 281 Pisarenko, V. V., 225 Pitha, J., 148 Pitha, P. M., 148 Platenberg, D. H. J. M., 134 Plato, V., 35 Plaut, B., 166 Plekhanov, V. G., 264 Pletcher, J., 159 Plieth, K., 279 PliSka, V., 143 Ploger, W., 133 Pobedimski, D. G., 231 Pogonowski, C. S., 195 Pokonova. Yu. V., 225 Polito, A.,‘ 167 Polivanov, A. N., 285 Pollard, D. R., 147, 227, 280 Polyachenok, L. D., 61 Polyachenok, 0. G., 61 Polyakova, A. A., 286 Poncet, J., 192 Pontis, H. G., 163 Poonian, M. S., 153 Popjiik, G., 167 Popovici, N., 129, 134 Porte, A. L., 126, 208, 268 Porter, J. W., 167 Posner, G. H., 194 Posternak, T., 150 Potti, P. G. G., 158 Prado, J. C., 272 Prahba, S., 117 Prakash, H., 224 Prasad, V. A. V., 42 ’

Predvoditelev, D. A., 264 Prentice, J. B., 97, 132, 261, 289 Priddle, J. D., 166 Priest, D. N., 121 Priestley, H. M., 264 Prihar, J. S., 163 Proctor, J. E., 214 Proctor, W. G., 139, 213 Pronin, I. S., 268 Proskurnina, M. V., 9, 129, 286 Proskuryakov, V. A., 225 Prout, C. K., 126, 280 Pudovik, A. N., 57, 82, 83, 86, 92, 93, 97, 104, 132, 138, 198, 207, 252, 256, 260, 263, 265, 266, 271, 274, 283, 288 Pudovik, M. A., 104, 266, 214

Pujol; R , 138 Pullman, B., 280 Purcell, T. A., 191 Putman. S. J.. 166 Pyrkin, R. I.,’73 Pytlewski, L. L., 272 Quimby, 0. T., 97, 132, 261, 289 uin L D 15, 30, 248, 255. 261. 562 Qureshi, A. A., 167 Qureshi, A. R., 85 Rabinovitz, M., 183 Racker, E., 151 Rackham, D. M., 243 Radloff, J., 32, 253 Radosavljevic, S. D., 215 Raevskaya, 0. E., 92 Raevskii, 0. A., 274 Raftery, M. A., 167, 248 Ragoonanan, D., 85 Rahn, B. V., 13 Rahn, P., 13 Raj Bhandary, U. L., 141, 149 1J A

Rajic, D. R., 283 Rakhimova, G. I., 288 Raksha. M. A.. 65 Ramaswamy, K.,274 Ramirez, F., 34,42, 43, 98, 115, 117, 181, 253, 280 Rammler, D. H., 145 Ramos, J. J. M., 265 Ranganthan, T. N., 223, 224. Rankm, D. W. H., 52, 53, 54,60,262,277,282,285 Rao, B. K., 274 Raphael, R. A., 191 Rassat, A., 140, 237 Ratovskii, G. V., 270 Rau. G., 159 Rauk, A., 35 Raymond, K. N., 280 Razumov, A. I., 58, 250, 251, 252, 259, 264

299

Author Index Razumova, N. A., 40,44 Razumovskii, S. D., 12,238 Razvodovskaya, L. V., 132 Redmore, D., 139, 252 Regitz, M., 79, 80, 135 Reich, E., 155, 159 Reichmann, M. E., 145 Reingold, J. D., 242 Reiss, J. G., 63 Remizov, A. B., 252, 259, 273, 274 Rengaraju, S., 139 Renthal, R. D., 169 Rettig, S. J., 227 Reuther, W., 16, 84 Reutov, 0. A., 173, 188 Reynard, K. A., 225 Rice, R. G., 225 Rich, T. C., 174 Richards, J. B., 157 Riddleston, B., 166 Ridley, D. C., 220, 277 Ridlington, J. W., 166 Rieke, R. D., 237,269,284 Riess, J. G., 36, 255 Righetti, P., 157 Robert, D. U., 36, 63 Robert, J. B., 15, 53, 140, 237,250,258, 267,282 Roberts, B. P., 231, 232, 235, 269, 270 Roberts, E.., 160 Roberts, J. D., 53,258,262 Roberts, J. R., 234 Roberts, P. J., 191 Robertson. J. M.. 280 Robertson; R. E.; 116 Robiette. A. G., 52, 281 Robin, Y., 169 . . Robinet, G., 275 Robins, R. K., 142, 143, 144 Robinson, C. N., 5, 130, 133 Roesky, H. W., 48, 67, 127, 134, 200, 207, 216, 22 1 Rogers, P. E., 234 Rohde, W., 155 Roman, F., 13 Romanov, G. V., 132 Rong, P. R., 111 Rosas, C. B., 161 Rose, I. A., 165, 166 Rose, S. H., 225 Rose, Z. B., 165 Rosenberg, M., 157 Rosing, J., 161 Rosini, G., 223 Ross, F. K., 181, 280 Ross, R. A. M., 188 Rottman, F. M., 155 Rowe, M. J., 156 Roychoudhury, R., 157 Rozental, D. A,, 225 Rozinov, V. G., 61 Rubenstein, M., 155 Ruckelhauss, G., 213, 237 Rudavskii, V. P., 127, 201, 21 0 Ruden, R. A., 184

Rudloff, E., 157 Rudolph, R. W., 53, 262 Ruhlmann, K., 4, 56, 70, 27 1 Ruelle, P., 140, 237 Ruterjans, H., 146 Ruff, J. K., 213 Ruppert, I., 67, 211 Russell, C. S., 169 Ruveda, M. A., 95, 125, 132, 241 Rybkina, V. V., 61 Rycroft, D. S., 262, 264 Sabherwal, I. H., 5 Sacher, R. E., 270 Sadowski, G., 215 Sadykov, A. S., 252 Saenger, W., 181 Safin, I. A., 269 Saito, H., 222 Saito, J., 225 Sakaki, K., 240 Sakurai, H., 229 Salakhutdinov, R. A,, 250, 251, 252, 259,264 Saleh, G., 10, 103, 205 Samarai, L. I., 272 Samitov, Yu. Yu., 44, 253,256, 260, 263, 266 Sammes, P. G., 242 Sampson, E. J., 118, 119 Sanchez, M., 35, 44, 45, 47, 104, 258, 259, 268 Sandmann, H., 1, 3 Sanger, A. R., 59 Sanin, P. I., 286 Santi, D. V., 166 Santoro, E., 286 Sanz, F., 279 Saran, A., 280 Saraswathi, N., 282 Sarma, R. H.. 248. 266 Sasaki; T., 148 Sasic, J. S., 215 Satchell, D. P. N., 158 Satge, J., 4, 56 Sato, N., 161 Saukaitis, J. C., 12 Saunders. D. G.. 98. 246 Savage, W. J., 53, 277 Savchenko, L. Y., 92 Savtant, J. M., 170, 284 Savicheva, G. A., 251 Savignac, P., 193 Savin, F. A., 276 Sax. M.. 159 Saxena,'S. B., 120 Scanlon, I., 30 Scartazzini, R., 188, 190 Schaad, L. J., 15, 282 Schadow. H.. 215 Schafer, W., 33 Schaffer, O., 28, 136 Scheiber, M., 9 Scheit, K. H., 145, 155 Scheler, H., 215 Scher, M. G., 157 Scherer, H., 135 Scherer, 0. J., 13, 203 '

Schetters, H., 155 Schiemenz, G. P., 254, 275 Schindler, N., 133, 201 Schirmer, R. H., 150 Schlak, O., 39, 257 Schlosser, M., 77, 177, 178 Schmid, H., 175, 177 Schmid, K. H., 204 Schmid, P., 270 Schmidbauer, H., 37, 62, 172, 180, 184, 199, 211 Schmidpeter, A., 47, 87, 201, 213, 214, 215, 268 Schmidt, P., 157 Schmidt, U., 133, 230 Schmidt, W., 82 Schmutzler, R., 35, 36, 39, 62, 63, 67, 129, 257, 259, 28 1 Schneider, N. S., 225 Schneider, P., 125 Schollkopf, U., 84, 194 Scholten, M. B., 143 Scholz, P., 16 Schott, H., 157 Schray, K. J., 165, 166 Schroder, R., 84, 194 Schroth, G., 172 Schuessler, D., 13 Schulman, S . G., 277 Schultz, G., 143 Schultz, K., 143 Schulz, D. N., 79 Schulz, G., 22, 187 Schulz, H. H., 146 Schwartz, A. W., 148 Schwartz. D. E., 146 Schweig, A., 32, 33, 253 Schweizer, E. E., 21, 22, 186

Schwendeman, R. H., 52 Schwenk. G.. 204 Schwyzer, R.',143 Scorrano, G., 138, 278 Scott, G., 239 Scott, R. J., 32, 202 Scriven, E. F. V., 244 Searle, H. T., 214 Secrist, J. A., tert., 145 Sedlov, A. I., 14, 75 Sedlova, L. N., 210 Seevogel, K., 172 Segal, H. L., 165 Segev, M., 220, 289 Selve, C., 69, 103 Semenii, V. Ya., 210 Semmler, E. J., 167 Sen Gupta, K. K., 111 Sequin, U.. 143 Sefo, S., 167 Sevin, A., 70 Seyden-Penne, J., 193, 266 Sevmour. S. J.. 253 Sgaramella, V.; 141, 152 Shagidullin, R. R., 57, 139, 273, 276 Shaidulin, S. A., 281 Shaikin, L. S., 281 Shall, S., 157 Shaper, J. H., 149 Shapiro, Y. E., 164

300 Shaw, M. A., 8 Shaw, N., 165 Shaw, R. A., 126,208,219, 254, 256, 267, 268 Shaw, R. W., 61, 277 Shaw, S., 284 Shawl, E. T., 227 Shearon, E., 5 Sheldrick, G. M., 52, 281 Sheldrick, W. S., 35, 62, 63, 281 Shepeleva, E. S., 286 Sherwood, P. M. A., 220, 277 Shevchenko, V. I., 209 Shevchuk, M. I., 188 Shibaev, V. N., 145 Shilov, I. V., 89 Shima, K., 229 Shimamura, K., 2 Shimizu, M., 159 Shimojo, N., 191 Shin, C., 87, 246 Shioiri, T., 125 Shipov, A. E., 259 Shnaiders, K., 259 Shokol, V. A.. 124. 127.

Shugar, D.,147 Shukla, R., 86, 92 Shuman, D. A., 143, 144 Siddall, T. H., 266 Sidky, M. M., 42, 93, 99 S!dwell,.R. W., 142 Siebeneick, H. U., 275 Sierakowska, H., 147 Sjewers, I. J., 118 Sigel, H., 151 Sigman, D. S., 150 Simalty, M., 17, 27, 264, 265 Simon, L. N., 142, 143, 144 Simonnin, M. P., 253 Simmon. P.. 85. 121 Sinikyna, N. I.,‘ 250 Sisidoi, K , 187 Sisler, H. H., 18, 224 Sizov, Y. A., 96 Skingle, D. C., 141 Skuballa. W.. 190 Slater, El C.,‘161 Slater, H. L., 176 Sletzinger, M., 161 Smalley, A. W., 20 Smets, G., 180, 204 Smith, B. C., 13, 219, 241, 254 Smith, C. W., 243 Smith, D. J. H., 20 Smith, H. E., 255 Smith, J. C., 156 Smith, M., 141 Smith, M. A., 156 Smith, P. F., 165 Smrt, J., 154 Snatzke, G., 278

Author Index Snead, J. L., 15, 229 Snell, E. E., 158 Snider, T. E. 6 260, 286 Snieckus. V.. 187 Snoble, K. A. J., 38 Snyder, J. P., 264 Snyder, S. L., 167 Sobanov, A. A., 92, 260 Sobeir, M. E., 13, 241 Soifer, G. B., 37, 269 Sokal’skaya, L. I., 274 Sokal’skii, M. A., 103 Sokoloski, E. A., 160 Sokolov, M. P., 251 Sollott, G. P., 15, 229 Solodovnikov, S. P., 82 Soma, N., 183, 266 Sommer, H., 154 Son, T. D., 261 Sondheimer, F., 191, 192 Songstad, J., 288 Sorensen, S., 263 Sorm, F., 150 Soroka, I. I., 126 Sosnovsky, G., 122 Soucy, M., 191 Soulen, R. L., 178 Soundararajan, S., 282 Southaate, R.. 190 Sowerby, b. B., 200, 217, 221,227 Speca, A. N., 272 Spencer, M., 157 Spencer, R. D., 145 SDerow. J. W.. 166 Spialter, L., 35 Spring, D. J., 31 Springer-Fidder, A., 194 Srivanavit, C., 77 Srivastava, K. C., 6, 73, 286 Stabrovskaya, L. A., 256 Stackhouse, J., 6, 13 Stadnichuk, M. D., 184 Staendeke, H., 6 Stafford, G. H., 164 Stahly, E. E.. 225 Stary, H., 215 Stec, W., 108,202,205,260 Stec. W. J.. 139. 213. 262. 263 Steffens, J. J., 118 Steger, E., 219 Stegmann, H. B., 198 Steiner. P. R.. 265 Steiner; R. F., 145 Stempfle, W., 172 Stepanov, B. I., 82, 213, 249, 276, 287 Stephenson, L. M., 37, 101, 238 Stern, P., 117 Sternbach, H., 155 Sterner, R., 166 Stetter, H., 237 Stevens, I. D. R., 71 Stewart, C. M., 143 Stille, J. K., 73, 76, 230 Stockel, R. F., 5 Stofko, J. J., jun., 175 Stocks, R. C., 262 *

,

,

,

Stokes, D. H., 265 Storey, P. M., 235 Strabovskaya, L. A., 252 Stratford, I. J., 156 Strating, J., 193 Streater, D. G., 142 Strecker, R. A., 15, 229 Struchkov, U. T., 279 Struszczyk, H., 225 Stuhler, H., 37, 62, 184 Stuehr, J. E., 138, 148,288 Stukalo, E. A., 66 Sturtz, G., 197 Stverteczky, J., 163 Subramanian-Erhart, K. E. C., 194 Sudakova, T. M., 92 Suerbaev, Kh. A,, 25, 271 Suss. G.. 46 Sugimura, T., 157 Sugimura, Y., 183, 266 Suleimanova, M. G., 206 Sullivan, C. E., 20 Sullivan, T. F., 289 Sultanova, D. B., 58 Sulzberg, T., 225 Sunamoto, J., 119, 120 Sundaralinaam. -~ M., 164 280 Supin, G. A., 284 Suridov, E. P., 16 Suter, R. W., 61 Sutherland, E. W., 143 Sutherland. J. K.. 196 Suzuki, S., ‘120,15 1 Suzuki, T., 159.. Svecov-Silovskij, N. I, 248. Sverdlov, E. D., 156 Svergun, V. I., 255 Svilarich-Soenen, M., 101 Swami. A. N.. 13. 241 Swartz; W. E.’, 213 Sy, J., 152 Symmes, C., 285 Symons, M. C. R., 82, Symons; 218, 236,237,269, 270 Symons, R. H., 141 Szabo, L., 163 Szabo, P.. Szabo. P., 163 Szafraniec, L. L., 140 ~

Tabushi, I., 192 Tadzhibaev, U., 278 Tagaki, W., 117 Tagima, K., 153 Takamatsu, M., 225 Takamizawa, A., 169 Takebayashi, N., 114, 153 Takeuchi, Y., 193 Tamagaki S., 240 Tamm, C., 143 Tamm, L. A., 17,90 Tamura, M., 187 Tan, H. W., 106 Tanaka, K., 283 Tanaka, T., 111, 283 Tang, R., 75 Taniguchi, M., 2 Tansey, L. W., 127, 160 Tasaka, K., 43, 253

301

Author Index Taub, D., 176 Taunton-Rigby, A., I53 Taylor, D. R., 55, 105, 285 Taylor, E. C., 173 Taylor, J. D., 179 Taylor, M. V., 242 Taylor, M. W., 273 Taylor, N. J., 56 Taylor, R. C., 4 Tazawa, I., 156 Tazawa, S., 156 Tebby, J. C., 8, 81, 171, 174,212,251, 264, 273 Teichmann, H., 18, 127 Tel, L. M., 273 Telegin, G. F., 221 Terao, T., 141, 152 Terent’eva, S. A., 104, 266 Tewari, R. S., 86, 92 Thalacker, R., 203 Thaller, V., 187, 188, 191 Thamm, H., 219 Thenn, W., 37 Theysohn, W., 173 Thiem, J.,- 95,-163 Thomas, K. M., 219 Thomas. P.. 163 Thomas, T.rD., 61, 277 Thompson, J. W., 273 Thompson, M., 277 Thynne, J. C. J., 285 Tikhonina, N. A., 114 Timofeev, V. E., 129 Timofeeva, T. N., 254 Timokhin, B. V., 270 Timoshiva, T. V., 138 Tochino, Y., 169 Todd, J. F. J., 286 Todd, S. M., 223 Tokuda, M., 289 Tokunaga, H., 243 Tolman, G. L., 145 Tomlinson, A. J., 35, 63, 256, 271 Tomlinson, R. H., 52 Tong, D. A., 208,268 Toppet, S., 241 Toube, T. P., 191 Towns, R. L. R., 21 Townshend, A., 284 Traeger, J. C., 284 Traynard, J. C., 98 Trefonas, L. M., 21, 279 Tret’yakova, A. Ya., 288 Trippett, S., 20, 38, 42, 252 Troev, K., 103 Trojna, G., 215 Tronchet, J. M. J.. 192 Trotter, J., 227 Trowbridge, D. B., 116,150 Tschudin, R. G., 261 Tsentovskii. V. M.. 288 Tsivunin, V. S., 57; 250 Ts’o, P. 0. P., 154, 156 Tsujimoto, N., 123 Tsvetkov, E. N., 73, 82, 254, 272,275, 287 Tucker, P. A., 227, 280 Tudrii, G. A., 86 Tukhar’, A. A., 213, 276 Tulyakova, T. F., 282

Tunemoto, D., 194 Tunggal, B. D., 135 Tuong, H. B., 178 Turley, P. C., 130 Turnblom, E. W., 24, 39, 252,256 Turner, J. L., 187 Turpin, R., 274 Tuttle, M., 242 Tuzova, L. L.,57,288 Uchic, J. T., 155 Uchic, M., 155 Ueda, K., 120, 151 Uesugi, S., 148, 154 Ugi, I., 34, 98, 115, 117 Ukai, T., 235 Ukigai, T., 136, 228, 286 Ullrey, J. C., 121 Usacheva, G. M., 55, 82 Utimoto, K., 187 Utvany, K., 39, 208 Uziel, M., 145 Uzlova, L. A., 188 Uznanski, B., 262, 263 Vachugova, L. I., 139, 273 Vaidya, 0. C., 9 Vaisberg, M. S., 259 Valpertz, H.-W., 59, 76 Van Bruggen, J. T., 160 van de Grampel, J. C.,208 Van den Berg, G. R., 134 Vanderhaughe, H., 241 Van der Veken, B. J., 272, 374

Van Wazer, J: R., 15, 52, 139, 204, 213,217,282 Varga, S. L., 267 Vashman, A. A., 268 Vasil’ev, A. F., 248, 282 Vasil’ev, Yu. N., 225 Vasyanina, M. A., 57, 138 Vedejs, E., 9,24,38,81, 187 Velker, E., 86 Velvis, H. P., 208 Venkateswarlu, A., 175 Vere Hodge, R. A., 191 Vereschchagin, A. N., 274 Vereshchagina, T. Ya., 268 Vereshchinskii, I. V., 60 Verheij, H. M., 165 Verheyden, J. P. H., 10, 69, 142 Verkade, J. G., 106, 108, 140, 260, 62, 266 Vermeer, H., 27 Vesper, J., 3 Vesterager, N. O., 121 Vetluzhskikh, I. M., 274 Vetter, H.-J., 55 Vicentini, G., 272 Vignais, P. M., 164 Vijayraghavan, N. V., 283

Vikane, O., 288 Vikane, T., 140 Viktorov, A. V., 164 Vilkov, L. V., 248,281,282 Villar-Palasi, C., 145 Vinogradov, L. I., 260,263 Vinogradov, V. L., 65 Vinogradova, V. S., 44, 86, 253, 260 Viricel, M., 289 Viswanathan, C. V., 289 Vix, V. A., 255 Vlietinch, A., 241 Voichenko, N. M., 225 Volkova, L. M., 225 Volkova, V. A., 289 Volkovitskii, V. N., 59 Volland, B., 59, 76 Vollhardt, K. P. C., 191 Volodin, A. A., 207, 222, 223 von Reyendam, J. W., 7 von Strandtmann, M., 180 Vorkunova, E. I., 235, 269 Vornberger, W., 172, 199, 21 1 Vorobiev, M. D., 54 Vovsi, B. A., 109 Voziyanova, 0. F., 86, 182 Wadsworth, W. S., jun., 106, 121 Wagner, A. J., 227, 280 Wagner. D.. 142 Wagner; F. ’A., 253 Wahid, A., 282 Wahl, G. M., 150 Walker, B. J., 93, 109, 173, 259 Walker, T. O., 5 Wallace, R. A., 283 Walters, D. B., 4 Walther, B., 109 Wang, C. S.-C., 60 Wantuck, J. W., 161 Ward, A. F., 278 Ward, D. C., 159 Ward, P., 13 Ward, R. S., 8 Warren, C. D., 157 Warren, S. G., 70, 71, 92 Watanabe, T., 158 Watkins, G. L., 188 Watson, R. R., 157 Watt, D. S., 194 Watts. G. B.. 233. 269 Weber, B., 79, 135 Weber, G., 145 Weber, H., 141, 152 Webster, J. M., 192 Webster. K.. 270 Weedon; B.*C. L., 191 Wegener, W., 16 Wehman, A. T., 21, 186 Wehrli,. F. W., 253 Weidlein, J., 37, 62 Weigert, F. J., 262 Weingand, C., 21 5 Weise, M. J., 164 Weissbach, H., 152

302

Author Index

Wells, D., 110, 242 Wells, M. A., 164 Welter, W., 80, 135 Wendler, N. L., 176 Weringa, W. D., 285 West, T. S., 278 Westheimer, F. H., 264 Wetzel, R. B., 72, 263 Whalen, R. G., 165 Whistler, R. L., 144 Whiteford, R. A., 53, 277 Whitehead, M. A., 258 Whitehouse, N. R., 192 Whiteley, J. M., 142 Whittle, P. J., 38, 352 Wiberg, N., 204 Wider de Xifra, E. A., 149 Wjeber, M., 51, 111 Wiebers, J. L., 156, 157 Wielesek, R. A., 233 Wiese, P. M., 289 Wiezer, H., 221 Wightman, R. H., 153 Wilfinger, H.-J., 19, 40 Wilhelm, G., 159 Wilhite. D. L.. 35 Wilke, G., 172 William, A., 5 Williams, A., 117, 120 Williams, D. A., 219 Williams, D. H., 8 Williams. D. J.. 277 Williams; F., 270 Williams. J. C.. 237. 269.

:. R..

, M., 105

70. 92

D. F., 161 1. B.. 116. 167 Wilson; I. F.,' 171,'174, 251 Wilson, J. D., 84 Wimmer, E., 141 Wingfield, J. N., 224, 227 Wins, P., 167 Wintermyer, R. L., 140 Witkowski, J. T., 142 Witt, J. D., 273 Wolf, J. F., 179 Wolf, P. L., 147 Wolf, R., 35, 44,45,46,47, 104, 258, 259, 268, 278 Wolf, w., 180 Wolfe, S., 273 Wong, S. C. K., 169, 212 Wood, D. J., 248, 266

Wood, H. G., 165 Woods, M., 13, 219, 241, 254, 256, 267 Woodward, R. B., 188, 190 Woplin, J. R., 67, 129, 259, 26 1 Wright, R., 153 Wunsche, C., 287 Wustner, D. A., 134 Wykes, J. R., 159 Wynberg, H., 68, 193 Yabusaki, K. K., 164 Yakshin, V. V., 214 Yakutin, V. I., 103 Yakutina, D. A., 270 Yamada, K., 199 Yamada, R. H., 149 Yamada, S., 125 Yamada, T., 141, 152 Yamaguchi, A., 194 Yamamoto, D. M., 116, 150 Yamashita, M., 235 Yamauchi, K., 128 Yamazaki, N., 109 Yanagida, S., 66 Yang, I. Y., 158 Yanik, B., 222 Yano, J., 154 Yarkova, E. G., 271 Yasnikov, A. A., 120 Yastrebova, G. E., 82, 283 Yasuhara, A., 177, 193 Yasumoto, M., 154 Yato, T., 265 Yee, K. C., 140 Yeh, H. J. C., 261 Ykman, P., 180, 204 Yogo, Y., 141 Yokoe, M., 66 Yoneda, S., 265 Yonezawa, Y., 87, 246 Yoshida, H., 11 1 Yoshida, Z., 265 Yoshidome, H., 119 Yoshimura, J., 87, 246 Younathan, E. A., 254 Young, R. G., 150 Yow, H., 61, 282 Yoza, N., 289 Yu, C. I., 167 Yurchenko, R. I., 212,213, 276, 288

Yurchenko. V. G..,212.213 , 276 Yurzhenko, T. I., 210 Yvernault, T., 122 Zagidullina, D. Sh., 288 Zagnibeda, D. M., 201 Zagudaeva, T. A., 128 Zagurskaya, L. M., 4, 13, 259 Zakharkin, L. I., 1 Zakharov, K. S., 4, 13, 259 Zakharova, N. M., 96 Zaripov, N. M., 281 Zaret, E. H., 122 Zarkadas, A., 14 Zaske, P., 279 Zavalishina, A. I., 289 Zavarikhina, G. B., 128 Zawadzki, S., 114 Zayed, M. F., 99 Zbiral, E., 21, 22, 24, 187, 198

Zbozny, M., 7 Zdorova, S. N., 84 Zeiss, W., 87, 213, 214 Zelawski, Z. S., 176 Zelentskii, S. N., 223 Zerba, E. N., 125, 132,241 Zhdanov, Yu. A., 188 Zheshutko, V., 222 Zhmurova, I. N., 83, 212, 213, 276, 288 Zhubekova, M. N., 1 Zhuravleva, L. P., 58 Ziehn, K.-D., 186, 205 Zimin, M. G., 92, 260,263 Zimmermann, R., 172 Zinkovskii, A. F., 92, 93, 288 Zishka, M. K., 150 Zoer, H., 227 Z'Ola. M. I.. 58 Zolotareva, ' L. A., 210, 213, 276 Zoroastrova, V. M., 86 Zsakb, I., 134 Zsindely, J., 175 Zuleski. F. R.. 143 Zumwald. J.-B.. 192