Organophosphorus Chemistry (SPR Organophosphorus Chemistry (RSC)) (v. 3)

A Specialist Periodical Report

Organophosphorus Chemistry Volume 3

A Review of the Literature Published between July 1970 and June 1971

Senior Reporter

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

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

D. J. H. Smith, The University, Leicesfer J. C. Tebby, North Staffordshire Polytechnic 6. J. Walker, Queen's Universify of Belfasf

ISBN : 0 85186 026 5 @ Copyright 1972

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

Organic fornrulue composed b y Wrighr’s Symbolser merhod

I’riiitcd in Grrat Brituin by John Wright uiitl . Y i m l.td, n t The Stonebridge Press, Bristol HS4 5 N / J

Foreword

This third volume continues the pattern set by its predecessors and covers the literature available to the Reporters from July, 1970, to June, 1971. The highlight for many organophosphorus chemists during this period was the EUCHEM Conference organised by Professor Leopold Horner and held at Schloss Elmau in March-April, 1971. Apart from the thriving state of organophosphorus chemistry, the chief impression gained by many of the participants was of a general erosion of the simple mechanistic pictures adequate in this field over the past ten years. The advent of pseudorotation, the precise details of which threaten to become controversial, and the increasing volume of data which cannot be accommodated within the framework of existing ideas promise exciting, if occasionally confusing, developments for report in subsequent volumes. S. T.

Contents

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

I Phosphines 1 Preparation A From Halogenophosphine and Organometallic Reagent B From Metallated Phosphines C By Reduction D Miscellaneous

1

2 Reactions A Nucleophilic Attack on Carbon (i) Activated Olefins (ii) Activated Acetylenes (iii) Carbonyls (iv) Miscellaneous B Nucleophilic Attack on Halogen C Nucleophilic Attack on Other Atoms D Miscellaneous

5 5 5 6

7 8 9 12 14

I I Phosphonium Salts I Preparation

16

2 Reactions A Alkaline Hydrolysis B Additions to Vinylphosphonium Salts C Miscellaneous

20 20 24 25

III Phosphorins and Phospholes 1 Phosphorins A Preparation B Structure C Reactions

26 26 27

2 Phospholes

28

27

vi

Contents

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett 1 Introduction

30

2 Acyclic

30

3 Four-membered

31

4 Five-membered A 2,2’-Bi pheny l ylenep hosp horanes B 1,3,2-Dioxaphospholens C 1,3,2-Oxazaphospholans D Miscellaneous

32 32 34

5 Six-membered

39

35 37

Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller 1 Halogenophosphines A Preparation B Reactions (i) Nucleophilic Attack at Phosphorus (ii) Biphilic Reactions with Dienes or Carbonyl Compounds (iii) Miscellaneous

40

2 Halogenophosphoranes A Preparation and Structure B Reactions

46 46

3 Phosphines containing a P-X

52

Bond (X = Si, Ge, or Sn)

40 42 42 44 45

48

Chapter 4 Phosphine Oxides and Sulphides By J. A. Miller 1 Bonding and Structure

54

2 Preparation A Using Organometallic Reagents B By Hydrolysis Reactions C By Oxidation D Miscellaneous

55 55 57 59 61

Contents

vii 3 Reactions

A Nucleophilic Reactions of the P=O Group B Electrophilic Reactions of the P=O and P=S Groups C Reactions not involving the P=O and P=S Groups

61 61

62 64

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

68

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

68 68 68 71 80 81 83 84 86 86 90

3 Phosphonous Acid and its Derivatives

91

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

95 95 1 00

105

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

I08 108 11 1

3 Miscellaneous

I19

I15

...

Cuntenrs

Vlll

Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W . Hutchinson 1 Mono-, Oligo-, and Poly-nucleotides A Mononucleotides B Nucleoside Polyphosphates C Oligo- and Poly-nucleotides D Nucleoside Thiophosphates E Physical Methods and Analytical Techniques

122 122 127 129 132 133

2 Coenzymes and Cofactors A Phosphoenol Pyruvate B Nicotinamide and Flavin Coenzymes C Nucleoside Diphosphate Sugars D Coenzyme A

134 134 135 136 137

3 Naturally Occurring Phosphonic Acids A Aminophosphonic Acids B Phosphonomycin

137 137 138

4 0xidat ive Phosphory lat ion

139

5 Sugar Phosphates and Phosphonates A Pentoses B Hexoses

141 141 142

6 Inositol Phosphates and Phospholipids A Inositol Phosphates B Phospholipids

144 144 144

7 Enzymology

145

8 Other Compounds of Biochemical Interest

147

Chapter 8 Ylides and Related Compounds By S. Trippett 1 Methylenephosphoranes A Preparation B Reactions (i) Halides (ii) Carbonyls (i ii) M iscell aneous

150 150 152 152 156 163

2 Phosphoranes of Special Interest

166

Contents

ix 3 Selected Applications of the Wittig Olefin Synthesis A Natural Products (i) Carotenoids

(ii) Prostaglandins (iii) Miscellaneous B Macrocyclics C Miscelianeous

170 170 170 173 173 176 178

4 Synthetic Applications of Phosphonate Carbanions

180

5. Ylide Aspects of Iminophosphoranes

183

Chapter 9 Phosphazenes By R. Keat 1 Introduction

187

2 Synthesis of Acyclic Phosphazenes A From Amides and Phosphorus(v) Halides B From Cyano-compounds and Phosphorus(v) Halides C From Azides and Phosphorus(rr1) Compounds D Other Methods

187 187 190 191 194

3 Properties of Acyclic Phosphazenes A Halogeno-derivatives B Aryl Derivatives C Other Derivatives

198 198 203 207

4 Synthesis of Cyclic Phosphazenes

210

5 Properties of Cyclic Phosphazenes A Amino-derivatives €3 Alkoxy- and Aryloxy-derivatives C Alkyl and Aryl Derivatives D Pseudohalogeno-derivatives

213 21 3 21 8 22 1 224

6 Polymeric Phosphazenes

224

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

226

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

230

Contents

X

2 Desulphurization and Deoxygenation Reactions

238

Chapter 11 Physical Methods By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy A Chemical Shifts and Shielding Effects B Studies of Equilibria and Reactions C Pseudorotation D Restricted Rotation E Inversion, Non-equivalence, and Configuration F Spin-Spin Coupling (i) JPP and JPM (ii) JPF (iii) Jpc (iv) JPH (v) JP(',II (4JPO(*,,H,JPN(,,,H, and JPNPH G Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies

248 248 254 255 258 259 262 262 263 263 263 264 267

2 Electron Spin Resonance Spectroscopy

269

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

270 270 27 I 27 3

4 Microwave Spectroscopy

275

5 Electronic Spectroscopy

276

6 Rotation and Refraction

278

7 Diffraction

279

8 Dipole Moments, Polarography, and Other Electrical Properties

283

9 Mass Spectrometry

285

268

10 pK and Thermochemical Studies

288

I1 Surface Properties

290

12 Radiochemical and Miscellaneous Studies

292

Author Index

293

A bbre viations

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

bisazoisobu tyroni tri le

1,5-diazabicyclo[5,4,O]undec-5-en dicyclohexylcarbodi-imide NN-d i met hylformamide di met hyl sulphoxide gas--liqui d chromatography hex a met h y I p h 0 sp ho r ic t ria mi de inorganic pyrophosphate nuclear quadrupole resonance tetracyanoet hylene tetrahydrofuran thin-layer chromatography

1

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

PART 1: Phosphines

1 Preparation A. From

Halogenophosphine and Organometallic Reagent.--Mesitylmagnesium bromide reacts with chlorodiethylphosphine and dichloroethylphosphine at - 10 "C in THF to yield mesityldiethylphosphine and dimesitylethylphosphine respectively.' Bis(dipheny1phosphino)methyl-lithium, from methyl-lithium and bis(diphenylphosphino)methane,gave the compound (1) with chlorodiphenylphosphine., (Ph,P),CHLi

+ Ph,PCl

-

(Ph,P),CH (1)

The six isomeric tris(methylthienyl)phosphines, e.g. (2), have been prepared by the reaction of methylthienyl-lithium derivatives with phosphorus t r i b r ~ m i d e . ~ Arylaluminium compounds (3) are obtained from the reaction of diphenylphosphine and triarylalumini~rns.~ The trimethylstannyl grouping in the phosphine (4) is replaced by diphenylphosphino upon reaction with chlorodiphenylphosphine.6

(Me,Sn),P (4)

'

+ 2Ph,PCI

-

Me,SnCl

+ (Ph,P),P

L. K. Il'ina, K. V. Karvanov, E. N. Karpova, A. I. Bokanov, and B. I. Stepanov, Zhur. obshchei Khim., 1970,40, 581 (Chem. Abs., 1970,73, 25 576). K. Issleib and H. P. Abicht, J . prakt. Chem., 1970, 312, 456 (Chern. Abs., 1970, 73, 109 844). H. J. Jakobsen, Acta Chem. Scund., 1970, 24, 2661. D. Giurgiu, I. Popescu, A. Ciobanu, M. Bostan, N. Voiculescu, and L. Roman, Rev. Roumaine Chim., 1970, 15, 1581 (Chem. Abs., 1971, 74, 53 893). H. Schumann, A. Roth, and 0. Stelzet, J . Organometallic Chem., 1970, 24, 183.

2

Orgumphosphorus Chemistry

A number of (polyhalogenoary1)phosphines have been synthesized by the addition of a chlorophosphine to a polyhalogenoaryl-lithium compound or a Grignard reagent.8 A complex reaction takes place when dichlorobis(tripheny1phosphine)nickel ( 5 ) is treated with excess methylmagnesium bromide in ether.' Detectable amounts of benzene, toluene, and biphenyl are formed, together with mixed phosphines. Nickel appears to be necessary for the substitution reaction since triphenylphosphine alone does not react with the Grignard reagent .

+ MeMgBr

(Ph,P):NiCI,

----+

PhH

(5)

+ PhMe + Ph, + Ph,MeP + PhMe,P

Good yields of phosphines have been obtained* by the simultaneous addition of an organolithium compound and an alkyl chloride to a solution of a cyclopolyphosphane (6). (R'P),

+ nLiR2 + nR3Cl

(6)

-

nR1R2R3P+ nLiCl

R', R2, R3 = alkyl, R3Si, R,Ge, or R3Sn

B. From Metallated Phosphines.--Lithium diphenylphosphide and ethylene oxide produce (7), which when added to chlorodibutyl- or chlorodiphenylphosphine yields 2-diphenylp hosphinoethyl p hosphini tes (8). @

Ph2PLi

+

/

\

H,C-CH,

--+ Ph,PCH2CH20Li

Ph,PCH,CH,OPR, (8)

R

= Ph,

n-C,H,

8-Quinolylphosphines have been prepared from the reaction of 8-chloroquinoline and potassium diphenylphosphide, or the quinolyllithium derivative and a chlorophosphine.1° A phenyl group can be cleaved, with lithium, from alkylphenylphosphines to give lithium alkylphenylphosphides, which with diphenylvinyl-

* lo

S. S. Dua, R. C. Edmondson, and H. Giiman, J . Organometallic Chem., 1970,24, 703. M. L. H. Green, M. J. Smith, H . Felkin, and G. Swierczewski, Chem. Comm., 1971,158. M. Schmidt and W.-R. Neeff, Angew. Chern. Znternat. Edn., 1970, 9, 807. S. 0. Grim, A. W. Yankowsky, and W. L. Briggs, Chem. and Ind., 1971, 575. K. Issleib and M. Haffendorn, 2. anorg. Chem., 1970, 376, 79 (Chem. A h . , 1970, 73, 77 333).

Phosphines and Phosphonium Salts

3

phosphine l1 produce good yields of the expected unsymmetrical di tertiary phosphines (9). RPhPCH2CH2PPh, (9; R = alkyl)

The ditertiary phosphines (1 l), prepared from the corresponding alkyl chloride and lithium diphenylphosphide react with sodium in liquid ammonia to give the phosphines (12).

Phosphides add to the double bond of mp-unsaturated carbonyl compounds l 3 to give the phosphines (13). PhCH=CHCOR1

+ MPHR2

----+

R2PHCHPhCH2COR1 (13)

R1 = Me, Ph; R2 = Ph, C,H,, The organometallic phenylphosphines (14) are obtained from the reaction of lithium phenylphosphide and Group IV chlorides.14 PhPHLi

+ MsMCI

-

PhPHM(Me), (14)

M = Si, Ge, or Sn

Phosphine and lithium aluminium hydride form lithium tetraphosphinoaluminate (1 5 ) which reacts with trimethyltin chloride Is to give the phosphine (16). 4Me3SnC1

+ LiAKPH,), (15)

-

LiCl

+ AICI, + 4Me3SnPH, (16)

The reaction of dipotassium phosphide with dichlorodiphenylsilane and diphenylgermanium dichloride l6 yields the dimers (1 7) and trimers (1 8). 3-Chloroprop-1-yne reacts with sodium diphenylphosphide in liquid ammonia to give diphenylprop-1-ynylphosphine (1 9). However, when the addition is carried out in THF a mixture of the prop-2-ynylphosphine l1 la

lS

S. 0. Grim, R. P. Molends, and R. L. Keiter, Chem. andInd., 1970, 1378. K. Sommer, 2. anorg. Chern., 1970, 376, 37 (Chem. Abs., 1970,73, 77 326). K. Issleib and P. V. Malotki, J . prakr. Chem., 1970, 312, 366 (Chern. Abs., 1970, 73, 77 337).

l4

l5 lo

P. G. Harrison, S. E. Ulrich, and J. J. Zuckerman, J . Amer. Chem. Soc., 1971, 93, 2307.

A. D. Norman, J . Organometallic Chem., 1971, 28, 81. H. Schumann and H. Benda, Chem. Ber., 1971, 104, 333.

4

Organophosphorus Chemistry

(20), the allenylphosphine (21), and the prop-1-ynylphosphine (19) is obtained. If excess diphenylphosphide is avoided, pure diphenylprop-2ynylphosphine (20) is the product. These products presumably arise from an S Nreaction ~ followed by a prototropic rearrangement.”

TI

Diferrocenylphenylphosphine and ferrocenyldiphenylphosphine have been prepared by a modified procedure.ln C. By Reduction.---The cyclic secondary phosphines phospholan and phosphorinan have been prepared by reduction of the corresponding chlorophosphines with lithium aluminium hydride.le The reduction of optically active methylphenyl-n-propylphosphine sulphide with lithium aluminium hydride proceeds with 100% retention,20 whereas the reaction of phosphine oxides with lithium aluminium hydride leads to racemization.21

2o

W. Hewertson, I. C. Taylor, and S. Trippett, J . Chetn. SOC.(C), 1970, 1835. C. E. Sullivan and W. E. McEwen, Org. Prep. Proced., 1970, 2, 157. K. Sommer, 2. anorg. Chem., 1970, 379, 56. R. Luckenbach, Tetrahedron Letters, 197 I , 2 177. P. D. Henson, K . Naumann, and K . Mislow. J . Atuer. Chem. Suc., 1969, 91, 5645.

Phosphines and Phosphonium Salts

5

D. Miscellaneous.- The base-catalysed addition of diphenylphosphine to excess vinyl isocyanide 22 gave (22). However, the reaction of phenylPh,PH

+ CH,=CHNC

THE'

Ph2PCH,CH,NC (22)

phosphine with excess vinyl isocyanide gave the azaphosphole (23). The addition of phenylphosphine to 2,6-cycloheptadien-l-oneat 140 "C gave a mixture of (24) and (25) which can be separated by sublimation or di~tillation.~~ rn-Nitro-substituted triaryl- and alkyldiaryl-phosphines can be prepared by the nitration of methoxymethylphosphonium salts with nitronium tetrafluoroborate.24

2 Reactions A. Nucleophilic Attack on Carbon. -(i) Activated OZeJins. A study of triarylphosphine-catalysed dimerization of acrylonitrile to 2-methyleneglutaronitrile (26) and 1,4-dicyano-l-butene (27) has established a balance between phosphine nucleophilicity and protolytic strength of the solvent.25 The reaction of methyl vinyl ketone with triphenylphosphine in triethylsilanol gave only 3-methylene-2,6-heptadienone(28). CH,=CHCN

Ar3P

NCC(: CH,)CH,CH2CN

+ NCCH=CHCH,CH,CN (27)

(26)

MeCOCH :CH, 22 2a *4

EtsPiOH Ph3P +

MeCOC(: CH2)CH2CH,COCH: (28)

R. B. King and A . Efraty, J. Amer. Cheni. Soc., 1971, 93, 564. Y.Kashman and 0. Awerbouch, Tetrahedron, 1970, 26, 4213. G. P. Schiemenz and K. Rohlk, Chetn. Ber., 1971, 104, 1219. J. D. McClure, J. Org. Cheni., 1970, 35, 3045.

Organophosphorus Chemistry 0-

0

4-Methylene-2,6-di-t-butyl-2,5-cyclohexadien-l-one reacts with tributylphosphine 28 in benzene to form an isolable betaine (29). For the reaction of tetramethyldiphosphine with butadiene see Chapter 10, Section 1. (ii) Acfivafed Acefylenes. The reaction of triphenylphosphine with phenylacetylene has been investigated in more The rearrangement has been shown to proceed via the vinylphosphonium salt (30).

Ph,P

+

HCiCPh

+

H,O ---+

+

OH-

Ph,P*CH:CHPh (30) OH I Ph3PCH:C H Ph

T i In a similar rearrangement dibenzophosphorin oxides (3 1) have been prepared from the reaction of dibenzophosph(rr1)oles with methyl propiolate.28 Some ring expansion occurs even when R = benzyl, presumably because of the difficulty of putting benzyl in an apical position in the intermediate phosphorane. The reaction of triphenylphosphine with an excess of dimethyl acetylenedicarboxylate2g gives not only the phosph(v)ole (32) but also a cyclopen tenylidenephosphorane (33). 26 27

28 29

W. H. Starnes and J. J. Lauff, J . Org. Chem., 1970, 35, 1978. E. M. Richards and J. C. Tebby, J . Chem. SOC.(C), 1971, 1059. E. M. Richards and J. C. Tebby, J . Chem. SOC.(C), 1971, 1064. N. E. Waite, J . C. Tebby, R. S. Ward, M. A. Shaw, and D. H. Williams, J . Chem. SOC. (C), 1971, 1620.

a-0

Phosphines and Phosphonium Salts

\

7

+ HCiC-CO,Me +

/

H,O +

I

/ \

R

R

R

=

CH:CHCO,Me

k-'

Me, Ph, or PhCHz

OH-

dH2c O4 / K

(31)

Ph3P

+

Me0,C - CO.,Me Me0,CC i CCO,Me---+ McO,C (&Me \ p PI1

+

C0,Mc M e 0 2 C p M ' Me0,C 0

PI1*

PPh, (33) 20%

(32) 40";

(iii) Carbonyls. Bifluorenylidenes (34) are formed from tributylphosphine

and fluorenones in the absence of solvent. When the reaction is carried out in a solvent having abstractable hydrogens a complex mixture is produced. Tetraphenylcyclopentadienone and tributylphosphine gave (35) and a hydrocarbon. These reactions are thought to proceed through carbene or carbenoid intermediate^.^^

X PI1

=

-

H or Br Ph

Q1o PI1 -

(34) 4(%

Ph

+ Bu3P --+ Ph

- Ph

Ph - Ph

[Itci + Ph Ph-

C58H40

Ph

( 3 5 ) 28:; ( - )-Methylphenyl-n-propylphosphinereacts with halogenoketones 31 to give ketophosphonium salts (36) with retention of configuration at phos8o 91

I. J. Borowitz, M. Anschel, and P. D. Readio, J . Org. Chern., 1971, 36, 553. I. J. Borowitz, K. C. Kirby, P. E. Rusek, and W. E. R . Casper, J . Org. Chern., 1971,

36, 88.

8

Organophosphorus Chemistry

phorus, and enol phosphonium salts (37) with inversion of configuration at phosphorus, indicating that the former result from S N displacement ~ of halide ion by the phosphine and the latter from phosphine attack on halogen followed by recombination of the resulting ion pair. t

c1

PI<, I PhCUC~II% C1-

I

Z

-

16.1"

Br

Aldehydes and diethyl(triethy1germyl)phosphine give (38) while unsaturated aldehydes and ketones form 1,4-dipolar addition products (39), presumably via ionic cleavage of the germanium-phosphorus bond. Hydrolysis of these compounds produces the y-substituted phosphorus aldehydes or ketone^.^?

(iu) Miscellaneous. trans-2-Et hyl thiolocyclohexylphenylphosphine(40) can be prepared 33 from sodium phenylphosphide and cyclohexanethi-iran, followed by reaction with ethyl iodide. Treatment of 2-thioxo-l,3,2-dioxaphosphorinanswith triphenylphosphine gives (41). The reaction is thought to proceed as 32 33 34

J . Satge, C. Couret, and J. EscudiC, J . Organometallic Chem., 1970, 24, 633. E. Wenschuh and K. P. Rudolph, 2. anorg. Chem., 1970, 380, 7 . N. H. Phuong, N. T. Thuong, and P. Chabricr, Compt. rend., 1970, 271, C, 1465.

Phosphines and Phosphonium Salts

9

' I'I'h,, B. Nucleophilic Attack on Halogen. - -(R)-( + )-2,2-dimethylpropan(*H)ol has been converted to the chloride with inversion of configuration using triphenylphosphine and carbon tetrachloride. The corresponding reaction using carbon tetrabromide gave the bromide with considerable racemizati Geranyl chloride can be prepared from geraniol by the careful use of triphenylphosphine in carbon t e t r a ~ h l o r i d e . ~ ~ Tris(dimethy1amino)phosphine reacts with carbon tetrachloride to form the complex (42) which can be used to form the enol esters (43) from acid anhydride^.^' Similarly,38 aldehydes form the alkenes (44), and esters or amides of trichloroacetic acid are converted to glycidic (Mc,N),P

+

CCll

THF

-- 78

c

f

CI-$(NM~,)~

CCI,

(42) CCI, (KCH,CO)ZO

+ (42)

---+

I

KH2C-C-02CCH,R I 0- 'tP(NMc,),

I

C1

n

CCI, II RH2C-C-O,CCH,

CCI. -Cl

R +--

(43) KCHO 3L 3R

:I7 :In

as

+ (42)

I 2

4 &Iy

R €i2C-C -0 , C CH, R I (OP(N Mc, 1,

- - - - - - - _+

RCH =CC'I,

(44) R. G . Weiss and E. I. Snyder, J. Org. Chetn., 1971, 36, 403. C . B. Hunt. D. I;. MacSweeney, and R . Kamagc. Tetrohedron. 1971, 27, 1491. J. Villioras, Ci. Lavielle, and J.-C. Combret, Coritpt. rend., 1971, 272, C', 691. J.-C'. Combret, J. Villieras, and G. Lavielle, Terrohedron Letters, 1971, 1035. J. Villieras, G. Lavielle, and J.-C. Combret, B i d . SOC.chirn. Frame, 1971, 898.

10

Organophosphorus Chemistry

The simultaneous addition of ammonia or amines and carbon tetrachloride to phosphines *O yields aminophosphonium chlorides (45). Ph,P

+ R'R2NH + CCl,

[Ph3PNR'R2]+ C1-

+ HCCl,

(45)

R', R2 = alkyl, aryl, H The use of the triphenylphosphine-carbon tetrachloride adduct for dehydration reactions appears to be a very simple way of synthesizing ni triles from amide~,~' carbodi-imides from u r e a ~ and , ~ ~isocyanides from monosubstituted f o r m a m i d e ~ . All ~ ~ of these reactions involve the simultaneous addition of triphenylphosphine, carbon tetrachloride, and triethylamine to the compound to be dehydrated. The elimination of the elements of water is stepwise. An adduct, e.g. (46), is first formed, chloroform being eliminated, which decomposes to produce hydrogen chloride and the dehydrated product.

(46)

[HCII

+

RNC

+

Ph3P0

J + CHCI,

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide syntheskq4 Condensation of N-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. /3-Bromo-/3-nitrostyrene and triphenylphosphine in dry benzene gave the phosphonium bromide (47). Using methanol as the solvent, the rearranged product (48) was formed, possibly via an azirine intermediate.46 Substituted p-bromo-p-nitrostyrenes yield the phosphoranes (49) and a phosphonium When the aryl group is electron-donating, the reaction follows a different course to form the styrene (50) by initial attack of the phosphine on halogen. The phosphetans (51) react with one equivalent of chlorine to give but-3-enylhalogenophosphines, which can be cyclized by heating or by treatment with halogen or aluminium chloride to the A3-phospholen 'O

" IZ 43

'' ''

R. Appel, R. Kleinstuck, K. D. Ziehn, and F. Knoll, Chem. Ber., 1970, 103, 3631. R. Appel, R . Kleinstuck, and K . D. Ziehn, Chem. Ber., 1971, 104, 1030. R. Appel, R. Kleinstuck, and K. D. Ziehn, Chem. Ber., 1971, 104, 1335. R. Appel, R. Kleinstuck, and K. D. Ziehn, Angew. Chem. Internat. Edn., 1971, 10, 132. L. E. Barstow and V. J. Hruby, f. Org. Chem., 1971, 36, 1305. C. J . Devlin and B. J . Walker, Chem. Comm., 1970, 917. C. J. Devlin and B. J. Walker, Tetrahedron Letrers, 1971, 1593.

Phosphines and Phosphonium Salts

11

containing a small amount of A2-phospholen.47The use of bromine affords the phospholen hydrobromides, which can be converted to the free phospholens by treatment with one equivalent of alkali. 0I -t PhCH= C = N -0-PPh,

PhCH:C(Br)NO,

Br-

+

I

Ph,P

Ph,I' -CH,-

,OMe

-t

N = C,

Ph, P -CH CN

P 11

Ar

=

McOH

3Ph,P --+ Ph,P=CCHO I Ar p-O,NC,H,,iII-O,NCtiHI (49)

ArCH:C(Br)NO,

4

NO, ArCH:C:

--+

k~ Br

Ph,P:

47

2

ArCH:CNO,

PI1 I

+

Ph,PRr

+

4- Ph3P-N=PPh3

MeOH

Br-

ArCH:CHNO, (50)

J. R. Corfield, M. J. P. Harger, R. K . Oram. D. J. H. Smith, and S. Trippett, Chem. Comm., 1970, 1350.

12

Organophosphorus Chemistry

C. Nucleophilic Attack on Other Atoms.-Amidoximes have been shown to react with tris(dimethy1amino)phosphine 48 by displacing dimethylamine to give the phosphine oxides (52), but some N-substituted aromatic amidoximes give derivatives of (53).49

N-OH KC<

NHR R = H or Ph

0 II

+

P ( N ~ . ~ c , )-, ,

\

NI1R (52)

a-Bromo-a-cyanosucci nimi des condense with triphenylphosp hi ne in benzene at room temperature to form iminophosphoranes (54). The reaction is thought 61 to involve the intermediate ( 5 5 ) . A cyclic intermediate may be involved in the reactions in refluxing benzene, which produce only the phosphonium salt (56). Br i

K2

Ii

R2 = Me

K’,K’

4n 40 6o

51

(54)

=

pJ-0 \

\

L. Lopez and J. Barrans, Compt. rend., 1970, 271, C , 472. L. Lopez and J . Barrans, Compt. rend., 1971, 272, C, 1591. M. F. Chaste and A . Foucaud, Tetrahedron Letters, 1971, 959. M. F. Chasle, E. Marchand, and A. Foucaud, Tetrahedron Letters, 1971, 963.

Phosphines and Phosphonium Salrs

13

A convenient aziridine synthesis using 2-iodoalkyl azides and triphenylphosphine has been The reaction is stereospecific and is thought to proceed by attack of the phosphine on azide:

’

I’Ph, I I 14%.,/N, ,,,ti

t

I*..

/N3

Me+1

c;-.I I

1’11,l’

Me

I{.,,

/

N - N =NPJ’h,

---+

c-c

I hl c

hlc(/C-Ci‘.\{ I hl c

\

Mc

Mercaptans have been oxidized with diethyl azodicarboxylate and triphenylph~sphine.~~ It is suggested that the formation of a chargetransfer complex (57) may be a key step in the reaction.

P Ph,

R

=

(57)

PI-”,PhCH,, Ph

F,C‘

CF, (58)

An ylide ( 5 8 ) is formed when tetrakis(trifluoromethy1)cyclopentadienone and triphenylphosphine are mixed in di~hloromethane.~~ Bis(trifluoromethy1)nitroxide displaces the dimethylamino-group from tris(dimethy1amino)phosphine 55 to form (59). (Me,N),P

+ (CF,),NO

-

(Me,N),PON(CF,),

+

Me,NON(CF,),

(59)

Various thiirans have been desulphurated to the corresponding ethylenes with triphenylphosphines.66 For other desulphuration and related reactions see Chapter 10, Section 2. 62

6s 68

A. Hassner and J. E. Galle, J . Amer. Chern. SOC.,1970, 92, 3833. K. Kato and 0. Mitsunobu, J . Org. Chem., 1970, 35, 4227. 0.M . Roundhill and G. Wilkinson, J . Org. Chem., 1970, 35, 3561. Y . 0. El Nigurni and H. J . Emeleus, J . Inorg. Nuclear Chem., 1970, 32, 3213. M. M. Sidky, M. R. Mahran, and L. S. Boulos, J . prakt. Chem., 1970, 312, 5 1 (Chenr. A h . , 1970, 73, 14 625).

14

Organophosphorus Chemistry

D. Miscellaneous.-A study of the racemization of ( +)-methylphenyl-npropylphosphine has shown that the rate of racemization has no dependence on solvent polarity and could not be correlated with any known solvent parameter^.^'

There is a good correlation between inversion barriers of phosphines and the electronegativity of the ligands. Mislow suggests that the electronegativity of the ligands alone is sufficient to account for the energy barriers for pyramidal inversion.58 The inversion barrier of acylphosphines is much lower than that of trialkylphosphines and is explained as arising from an enhanced ( p p ) z - conjugation of the phosphine lone-pair and the carbonyl group in the planar transition state relative to the pyramidal ground state.6B Optically stable racemic phosphines have been oxidized with one half equivalents of optically active peracid. The remaining phosphine, oxidized with perbenzoic acid, showed low optical activity, but the phosphine oxides obtained in the asymmetric oxidation were optically inactive.so Several t-alkylphosphines have been oxidized by aqueous alkali, resulting in the evolution of hydrogen gas. The only requirement for reduction appears to be the solubility of the phosphine in aqueous alkali R,P

+

7

’

0-€I r-oH

- OH

11,O

s R:,P’+ ;;‘I!

+ R,,PO

+

+ -okr

13~

1

The oxidation of (S)-( + )-methylphenyl-n-propylphosphinewith nitrogen tetroxide led to retention of configuration with considerable racemization, whereas oxidation with nitric acid gave the oxide with inversion of configuration.62 The use of triphenylphosphine and 2,2’-bipyridyl disulphide in oxidationreduction condensations has been extended to the phosphorylation of alcohols and phosphate^,^^ and to the preparation of S(2-pyridyl) phosphorothioates (60) which have been used for the synthesis of pyrophosphatess4 (see Chapter 6, Section 1).

(60) Oi

b8

6o 61

O4

H. D. Munro and L. Homer, Tetrahedron, 1970, 26, 4621. R. D. Baechler and K. Mislow, J . Amer. Chem. SOC.,1971, 93, 773. W. Egan and K. Mislow, J . Amer. Chem. Soc., 1971, 93, 1805. U. Folli and D. Iarossi, Boll. sci. Fac. Chim. ind. Bologna, 1969, 27, 223 (Chem. Abs., 1970, 73, 3984). S. M. Bloom, S. A. Buckler, R. F. Lambert, and E. V. Merry, Chem. Comm., 1970, 870. J. Michalski, A. Okruszek, and W. Stec, Chem. Comm., 1970, 1495. T. Makaiyama and M. Hashimoto, Bull. Chem. SOC.Japan, 1971, 44, 196. T. Makaiyama and M. Hashimoto, Tetrahedron Letters, 1971, 2425.

Phosphines and Phosphoniurn Salts

15

Triphenylarsine oxide transfers its oxygen to triphenylphosphine 65 in dichloromethane at 105 "C. Ph3AsO

+ Ph3P

105 "C

Ph3AS

+ Ph3PO

Trimethylphosphine and dimethylphenylphosphine form crystalline adducts (61) with chlorodiphenylphosphine.66 The adducts are in equilibrium with their starting materials in dichloromethane. Me,PR

+ Ph,PCI 7 [RMe,PPPh,]+ C1(61)

R = Me or Ph

Tertiary phosphines react with difluorophenylphosphine to give the corresponding difluorophosphorane (62) and pentaphenylcyclopentaphosphine. 1-Phenylphospholanand 1-phenylphosphorinan gave 1-chlorophospholan and 1-chlorophosphorinan respectively with phosphorus trichloride at 280 "C. Selective demethylation of (63) to the phenolic ether (64) has been achieved by the use of lithium diphenylph~sphide.~~ Treatment of the N-methylpyridinium salt of (65) with phosphiran 68 gave a solid complex, pentacarbonylphosphiranmolybdenum(0) (66).

(CH,),PH

+ [Mo(CO)J](65)

[(CH,),PH]Mo(CO), (66)

E. Ciganek, J . Org. Chem., 1970,35, 1725. F. Ramirez and A. E. Tsolis, J . Amer. Chem. SOC., 1970, 92, 7553. 13' R. E. Ireland and S. C. Welch, J . Arner. Chem. SOC.,1970, 92, 7232. * i ~R. Bausch, E. A. V. Ebsworth, and D. W. H . Rankin, Amgew. Chen. Internat. Edn., O6

1971, 10, 125.

Organophosphorus Chemistry

16

The addition of hydrogen chloride to the triple bond of alk-1-ynylphosThe ~ rate-determining phines in aqueous solutions is a r r a n s - a d d i t i ~ n . ~ step involves attack of chloride ion on the /I-carbon atom of the protonated a1k- 1-ynylphosphine : I&H)C=CR~

t- C I -

S,tl,\

> &(H)c=c(cI)R~

Thermal decomposition of 1-methyl-A3-phospholen in toluene at 356-

444 “C yielded butadiene as the primary product. The activation parameters are in agreement with a mechanism involving ring opening to a biradical followed by fragmentation into butadiene, phosphorus, and methyl radicals.7o

PART 11: Phosphonium Salts 1 Preparation A variety of aromatic phosphonium salts containing methoxy- and dimethylamino-groups has been prepared by the complex salt method :71 Ar,P

+ Ar’Br

+

NiUrz

Ar3PAr’Br-

The reaction of triphenylphosphine hydrobromide with phenylpropiolic acid gives a mixture of the ( E ) - and (Z)-isomers of 2-carboxy-1-phenylvinyltriphenylphosphonium bromide (67), not just the (2)-isomer as previously (E)-2-Ethoxycarbonyl-l-phenylvinyltriphenylphosphonium bromide (68) can be prepared in a similar reaction from ethyl phenylpropiolate. The addition of bromine to the ylide (69) gave a bromophosphonium salt which could be isolated.73 Dehydrohalogenation with dimethylformamide and lithium bromide afforded 1-phenylvinyltriphenylphosphonium bromide (70). PhCiCC0,IE

+ Phl,;€-I

,COJI

I’ll,

Br---)

t

1’

,C=C,

1’11,

+ l’ll:,l’ ,C==C’

If

Br-

l3r(67)

.s@ io

’I3

I1

4

G. Borkent, and W. Drenth, Rec. Trail. chim., 1970, 89, 1057. K. W. Egger and T. L. James, Trans. Faraday SOC.,1970, 66, 2560. L. Horner and U.-M. Duda, Tetrahedron Lettrrs, 1970, 5177. E. E. Schweizer and A. T. Wehman, J. Chrtn. Soc. ( C ) , 1970, 1901. E. E. Schweizer and A. T. Wehman, J. Chem. SOC.(C), 1971, 343.

‘~CO,t 1

Phosphitres and Phosphoitiunt Salts

17

Quaternization of the phosphine (71) with methyl iodide gave the phosphonium salt in quantitative yield. ( Disu bs t i tu ted-ami no) t ri pheny 1ph ospho n i u ni bromides (72) have been obtained from the reaction of triphenylphosphine dibromide and secondary amines in the presence of trieth~larnine.~~ Imido-bromides yield amidinotriphenylphosphonium salts (73) with iminophosphoranes. The fluxional nature of these salts is shown by the marked temperature dependence of the lH n.m.r. of the alkyl groups.7fi

R = alkyl, aryl

R'

I

N t

l',

-

\

c, \

- --

N

(73)

Quantitative yields of the phosphonium salts (74)are obtained when the salts (75) are heated with triphenylphosphine in polar 76

K. Fukin and R. Sudo, Bull. Chem. Sac. Jrrpan, 1970, 43, 1160. T. Winkler, W. von Philipsborn, J. Stroh, W. Silhan, and E. Zbiral, Chetn. Coinnr.,

76

V. I. Dulenko, N. S. Semenov, S. N. Baranov, and S. V. Krivun, Zhur. obshchei. Khinr..

74

1970, 1645.

1970, 40, 701 (Chem. Abs., 1970, 73, 14 943).

Organophosphorus Chemistry

18

Cyclopropylphosphonium salts are together with the phosphonium salts (76), in reactions of ylides with vinylsulphonium salts (77). The composition of the mixture depends upon the position of the initial attack by the ylide.

B Fa-

(77)

t.

Ph,P -CK / \

PhHC -CH2

BF4-

The reaction of trans-y-bromocrotonaldehyde with triphenylphosphine in ether gave (3-formylallyl)triphenylphosphonium bromide (78) while y-bromo-p-methylcrotonaldehydegave the rearranged salt (79). Acetals of diphenylphosphinoacetaldehydereact with hydrogen bromide in boiling glacial acetic acid 78 to give the cyclic salts (80). A one-step synthesis of the triphenylphosphonium salt (81) from linalool or geraniol and triphenylphosphonium bromide, with simultaneous

+

Ph P C H, C H :C H C i 10

BrCH,C(R):CHCHO

+

=Y

Ph,P

R=&

B I' -

(78)

cH, :c( MC) cH (C H O>

1111

(79) Br77

78

R . Manske and J . Cosselck, Tetrahedron Letters, 1971, 2097. M. J. Berenguer, J . Castells, R . M. Galard, and M. Moreno-Manas, TetrahedroriLc.tters, 1971, 495. K . C. Hansen, C. H . Wright, A. M. Aguiar, C. J. Morrow, R . M. Turkel, and N . S. Bhacca, J . Org. Chem., 1970, 35, 2820.

Phosphines and Phosphonium Salts

19

addition of methanol across the isopropylidene double bond, has been reported.Mo The mixture of salts obtained can be separated by fractional crystallization or t.1.c. The phosphonium salt (82) can be obtained by treatment of the vinyl alcohol (83) with triphenylphosphonium bromide.*'

'11,

Br-

Ferrocenyltriphenylphosphonium perchlorate (84) has been synthesized from iodoferrocene, tetrakis(acetonitrile)copper(I), and triphenylphosphine in nitromethane. The authors suggest 82 that iodoferrocene first forms the complex ( 8 5 ) which then breaks down uia a four-centred transition state to (84).

Polydentate phosphines such as I ,2-bis(diphenylphosphino)ethylene form salts (86) with phosphorus o x y ~ h l o r i d e . ~ ~ (m-Nitropheny1)triphenylphosphonium perchlorate can be prepared by the nitration of tetraphenylphosphonium perchlorate with concentrated nitric acid in sulphuric 8o

82

83

H. Kj~rsenand S. Liaaen-Jensen, Acta Chem. Scancl., 1970, 24,1488. D. E. Loeber, S. W. Russell, T. P. Toube, B. C. L. Weedon, and J. Diment, J . Chem. SOC.( C ) , 1971, 404. M. Sato, I. Motoyama, and K . Hata, Bull. Chem. Suc. Jnpan, 1971, 44, 812. E. Lindner and H . Beer, Chem. Ber., 1970, 103, 2802. T. A. Modro and A. Piekos, Bull. Acad. polon. Sci. SPr., Sci. chim., 1970, 18. 347 (Chenr. A h . , 1970, 73, 130 429).

20

Orgaitophosphorirs Chemistry

(S4) L Ph,PCH : CHPPh,

+

=

CH,,CN a n d ' o r CH,NO,

2POC1,,

-----+

0

0

II

II

[CI,PP(Ph),CH: CHP(Ph),PCI,]'+ 2CI(86)

2 Reactions A. Alkaline Hydrolysis. --The low kinetic isotope effect observed in the protonation of carbanions formed in phosphonium salt hydrolysis leads to the idea that there is little breaking of the phosphorus-carbon bond and correspondingly little transfer of a proton to the incipient carbanion in the transition state (87) of the rate-determining step.85

(87)

It has been suggested that the rate of displacement at phosphorus contained in a four-membered ring relative to displacement at acyclic phosphorus depends upon the electronegativity of the displaced group.86 All displacements at phosphorus are thought to involve the intermediate (88). Substitutions via (88) will involve retention of configuration at phosphorus when X is a highly electronegative group compared to Y, as the preferred pseudorotation will be to (89), followed by loss of the leaving group from the J. R. Corfield, and S. Trippett, Chrm. Conirii., 1970, 1267. J. R. Corfield, N . J. De'ath, and S. Trippett, Chem. Cornm., 1970, 1502.

Phosphines and Phosphonium Salts

21

apical position. If X and Y have comparable electronegativities the alternative pseudorotation to (90) becomes important and leads to loss of stereospecificity. This general idea has been expanded in a number of

I-

I

IPp.:N IY ' X

tl

1.1

Q

x'

Y

cp-x N' 'Y (89)

d

I-

c p: \- Y X N

1-

It has been shown that alkaline hydrolysis of both isomers of (91) gives the same ring-expanded oxide (92) of unknown geometry, presumably because rapid pseudorotation leads to equilibration of the intermediate^.^^ Alkaline hydrolysis of the dialkoxyphosphetanium salts (93) proceeds with almost complete lack of stereospecificity.88 In this case the authors hl c Mc

1' / \

PI1

Mc Mc

-

Mc' '0 (92)

R' = Me, R2 = Et or R1 = Et, K2 = Me (93)

87

J. R. Corfield, M. J. P. Harger, J. R . Shutt, and S. Trippett, J . Chem. SOC.( C ) , 1970, 1855. K. E. DeBruin and M. J. Jacobs, Chem. Comm., 1971, 59.

2

Organophosphorus Chemistry

22

assume that the intermediates are monoanions and hence pseudorotations from the initial phosphoranes would be irreversible and the product ratio a result of initial partitioning of the original phosphoranes. cis- and trans494) are decomposed by aqueous sodium hydroxide under identical conditions to give different mixtures of cis- and trans-4-methyl-1phenylphosphorinan- 1-oxides.8B The different ratios of oxides can be explained by assuming increased steric interactions in some of the pseudorotation pathways. Similar steric arguments are used to explain the ratios of oxides formed when the benzylphosphonium salts (95) are treated with aqueous alkali.23

+

OH___,

/ \

PhH2C

Ph

J j

0

6

Ph

Ph

6

The basic hydrolysis of A2- and A3-phospholenium bromides @O gives mixtures of (96) and (97), the ratio depending upon the conditions used. Ylide (98) formation can compete with phosphorane generation, particularly in media where anions are stabilized by solvation. Under these Me

Me

.....

Ph

K. L. Marsi and R. T. Clark, J . Amer. Chem. SOC.,1970,92, 3792. H. M. Priestley and J . P. Snyder, Tetrahedron Letters, 1971, 2433.

23

Phosphines and Phosphoniuni Salts

conditions thermodynamic control accounts for the conversion of both salts, predominantly to the acyclic products (97). Treatment of the A3-phospholenium salt (99) with aqueous alkali gave predominantly benzene and the oxide (100). It is suggested that here ring constraint leads to poor overlap of the n-bond in the ring with the p-orbital of the incipient carbanion which would lead to ring opening. Pseudorotation of the initial adduct followed by loss of the phenyl from the apical position becomes competitive.B1 Me

Steric crowding of intermediates, preventing groups from attaining correct conformations for maximum stabilization of departing anions, may be responsible for the observation that, in the alkaline hydrolysis of sterically crowded phosphonium the group lost need not be that which is most stable as the anion. Alkaline hydrolysis of 1 -iodomethyl-l,2,5-triphenylphospholium iodide 9 2 gave the bicyclic oxide (101) via the intermediate (102). Treatment of l-alkyl-l,2,5-triphenylphospholiumbromide with base produced a low yield of the phosphole (103).

(103)

The phosphoniaspiroalkane (104)was hydrolysed to the oxide (105)in refluxing aqueous potassium hydroxide 93 whereas the monocyclic analogue gave the oxide (106). 9a ny

J . R. Corfield, N. J . De’ath. and S. Trippett, J . Chem. Sor. ( C ) . 1971, 1930. A . N. Hughes and C. Srivanavit, Cunad. J . Chem., 1971, 49, 879. B. D. Cuddy. J. C. F. Murray, and B. J. Walker, Tetruhedrort Letters, 1971, 2397.

24

Organophosphoriis Chemistry

Considerable deuteriation occurs at the C-methyl group when the salt (107) is treated with methan[2H]ol-sodium meth~xide,'~ indicating that the resonance-stabilized anion (108) is formed as well as the ylide (109).

c;:;;

Me(CH,),P(:O)Et.,

The rates of hydrolysis of a variety of cyclic and acyclic phosphonium salts do not correlate with their 31Pchemical shifts.@* B. Additions to Vinylphosphonium Salts.-Sodium alkoxides react with vinylphosphonium salts (1 10) to give alkoxy-olefins (1 11) which can be hydrolysed to known #I-dicarbonyl Thiazolylmethylphosphonium salts (1 12) are formed in the reaction of vinylphosphonium salts (1 13) with thiourea or thi~acetamide,~~ showing that the initial attack is beta to the phosphonium grouping to give an intermediate immonium ylide.

I -

94

vs

D. W. Allen and J. C . Tebby, J . Chem. Soc. ( B ) , 1970, 1527. E. Zbiral, Tetrahedron Letters, 1970, 5107.

OK?

I‘h:,kH=CHCOK1

+

R2CCSNH2

x-

-

Ph,%6-CH--CHCOK1 I

s,

R ’ -= Me, Et or Ph R2 = N H , o r M c

f i y 2

C I

R2

x-

I

( I 12)

C. Miscellaneous.-Treatment of the phosphonium bromide (1 14) with one equivalent of butyl-lithium gave triphenylphosphine and benzylidenemethylamine via a Hofmann-like decomposition, whereas reaction with two equivalents of butyl-lithium resulted in the production of butyltriphenylphosphonium b r ~ m i d e . ’ ~

,CI l3

+

Ph,l’-N, CH,I’h 13r -

( 1 14)

2 h A A

l’h,PBu Br-

+

hlC

11”

‘TH2 1%

The reaction of organolithium compounds with dibiphenylenephosphonium iodide has been extended g6 to form the phosphoranes (1 15). The phosphonium salt (116) gave the phosphorane (117) with phenyllithium although i t has hydrogen atoms attached to carbon bonded to phosphoru~.~~

96

E. M.Richards and J. C . Tebby, J. Chern. Soc. (0,1970, 1425, Katz and E. W. Turnbloom, J . Amer. Chem. Suc., 1970, 92, 6701.

@’ T. J.

26

Organophosphorus Chemistry P I1

PI1 Ph1.i -__,

( I 17)

( 1 16)

Tributylphosphine displaces tris(hydroxymethyl)phosphine, triphenylphosphine, and, in poor yield, butylbis(hydroxymethy1)phosphine from the corresponding hydroxymethylphosphonium The use of tetra-alkylphosphonium salts to catalyse heterogeneous reactions involving anion transfer has been descri bed.es The crystal structure of the phosphonium salt (118) confirms that the compound is a diene and not a delocalized structure.1oo

( II S )

For the photolysis of phosphonium salts see Chapter 10, Section I . PART 111: Phosphorins and Phospholes 1 Phosphorins

preparation of phosphorins from pyrilium salts and tris(hydroxymethy1)phosphine has been extended to include phosphorins with indolyl and pyrrolyl groups as substjtuents.lol A new heterocyclic system, 1,6-diphosphatriptycene (1 19), has been prepared in a one-step synthesis by treating o-dichlorobenzene with white phosphorus in the presence of ferric chloride.lo2 A. Preparation.-The

( 1 19) OR 8'J

loo

lol

Io3

A. W. Frank and G. L. Drake, J . Org. Chem., 1971, 36, 549. C. M . Starks, J . Anter. Chent. Soc., 1971, 93, 195. R. L. R. Towns, R . Majeste, J . N. Brown, and L. M. Trefonas, J . Heterocyclic Chenz., 1970, 7,835. G . 1. Zhungietu, F. N . Chukhrii, and A. J. Tolmachev, Zhur. Vsesoyuz. Khim. obshch. itn D . 1. Mendeleeoa, 1970, 15, 590. (Chem. Abs., 1971, 74, 22 956). K. G. Weinberg and E. B. Whipple, J . Amer. Chem. Soc., 1971, 93, 1801.

27

Phosphiires and Phosphonium Salts

B. Structure.--The crystal structure of 1,1-bis(dimethylamino)-2,4,6triphenylphosphorin shows that this compound is very similar in structure to the 1-alkyl- and 1-alkoxy-substituted phosphorins.lo3 Theoretical calculations of the electronic structure of phosphorin indicate that the n-charge-distribution is different to that of pyridine and cannot be explained by simple resonance theory.lo4

C. Reactions.-l,2-Dialkylphosphorins rearrange on heating to 1,ldialkylphosphorins (1 20), which on further heating split off the substituents on phosphorus to yield 2,4,6-triphenylphosphorin.lo5 The reaction is not restricted to dialkyl-substituted phosphorins. Thermolysis of 1 -aryl- or 1 -alkyl-dihydrophosphorins (1 21) gives 2,4,6-triphenylphosphorinand the hydrocarbon, by migration of hydrogen. Substituted benzophosphabarrelenes (1 22) have been made from the reaction of phosphorins with benzyne.loG

I’ll I’ll

I

It2

-----f

K.

I ’ h , , ,’t (

ii

PI1

--PI1

120)

R

R

=

Hut or Ph

Substituted benzenes are obtained from the reaction of carbenes with phosphor in^.'^' The phosphepin (1 23) is thought to be an intermediate because the related compound (124) decomposes to a substituted benzene. Inr

loG lo*

lo’

U. Thewalt, C. E. Bugg, and A. Hettche, A t g e w . Chem. Internat. Edn., 1970, 9, 898. H. Oehling and A. Schweig, Tetrahedrott Letters, 1970, 4941. G . Mlrkl and A. Merz, Tetrahedron Letters, 1971, 1215. G. Miirkl, F. Lieb, and C. Martin, Tetrahedron Letters, 1971, 1249. G . Mlrkl and A. Merz, Tetrahedron Letters, 1971, 1269.

28

Organophosphorus Chemistry K'

C'HCI,

1%'

"0 ( 123)

2 Phospholes

A further report of the synthesis of phospholes from the conjugated-dienedi halogenophosphine adduct and DBU has appeared.lo8 Reduction of 1-benzyl-3,4-dibromophospholan oxide (1 25) with trichlorosilane, followed by debromination, gave 1-benzylphosphole. Determination of the molecular structure by X-ray analysis showed slight puckering of the ring with retention of pyramidal configuration at phosp h o r ~ ~ . ~ ~ ~

1-Phenyl-A2-phospholen-1-oxide (1 26) and trans-l,4-diacetoxybutadiene gave (127), which could be converted to the phosphole oxide. Reduction

lo*

F. Mathey, R. Mankowski-Favelier, and R. Maillet, Bull. SOC.chirn. France, 1970, 4433. P. Coggon, J. F. Engel, A. T. McPhail, and L. D. Quin, J. Amer. Chern. Sac., 1970, 92, 5779.

Phosphines and Phosphoniirm Salts

29

with trichlorosilane afforded the phosphindole ( I 28), which is easily oxidized by air and can be readily quaternized by benzyl bromide. The U.V.spectrum of (1 28) resembles that of 1-phenylindole very closely.11o

OAc

(127)

11"

T. H . Chan and L. T. L. Wong, Cunud. J . Chem., 1971, 49, 530.

2 Quinquecovalent Phosphorus Compounds BY S . TRIPPETT

1 Introduction This Chapter has been reorganized to take into account the increasing interest in the interaction of steric and stereoelectronic (electronegativity) factors in determining the relative stabilities of trigonal-bipyramidal phosphoranes and in particular in the preference of small rings for the apical-equatorial position, Quinquecovalent phosphoranes are now divided into categories according to the size of the smallest phosphoruscontaining ring. As before, the chapter deals only with stable compounds; those postulated as intermediates in substitutions at phosphorus are considered elsewhere.

2 Acyclic A simplified route to penta-arylphosphoranesl is by the direct action of

aryl-lithiums on the iminophosphoranes (1). (Ph0)3P:N.S0,.C,H,.Mc-p (1)

+

SArLi

---+

Ar,P (30-497<;)

Quinquecovalent phosphoranes readily undergo ligand exchange on treatment with organolithium compounds.l With alkyl-lithiums the resulting alkylphosphoranes give alkylidenephosphoranes, e.g. (2), by loss of benzene.

The nteta- and para-isoniers of the phosphoranes (FCBH4)3P(OEt)2 have been prepared from the corresponding phosphines and diethyl peroxide. From their l@F chemical shifts it was concluded that the groups a

M. Schlosser, T. Kadibelban, and G. Steinhoff, Annulen, 1971, 743, 25. B. C. Chang, D. Z. Denney, and D. B. Denney, J . Org. Chem., 1971, 36,998.

Quinquecovalent Phosphorus Compounds

31

P(OEt),(C6H,F), are weakly electron withdrawing both by induction and resonance. Tristrifluoromethylphosphineoxide with hexamethyldisiloxane gave the phosphorane (3). From the low-temperature lQFand lH n.m.r. spectra the (CF,),PO

+

(Me,Si),O -+ (CF,),P(OSiMe,), (3)

apical positions in (3) are probably preferentially occupied by trifluoromethyl groups. This is the first synthesis of a five-co-ordinate phosphorane directly from a phosphine oxide.

3 Four-membered The phosphoranes (4) and ( 5 ) have been obtained from the corresponding phosphines and diethyl peroxide. From the variable temperature 'H n.ni.r. spectrum of (9,below - 5 1 "C the phenyl group is locked in an equatorial position as in ( 5 ) , between - 5 1 and 30 "C the pseudorotation ( 5 ) + (6) is rapid on the n.m.r. time scale, and above 30 "C the pseudorotation (6) + (7) is rapid. In the latter pseudorotation the strain involved in Me

H

hle

I 'OEft OEt

Me

Me (7)

placing the four-membered ring diequatorial is partly compensated by the movement of a highly electronegative group from an equatorial to an apical position. Even so, the free energy of activation for this process, about 15 kcal mol-', testifies to the magnitude of the strain factor. The non-equivalence of the fluorine atoms observed5 in the leF n.m.r. spectra of the phosphoranes (8; R = Me or Et) at - 40°C has been

ti

R. G. Cavell and R. D. Leary, Chem. Conim., 1970, 1520. D. Z. Denney, D. W. White, and D. B. Denney, J . Anier. Chern. SOC.,1971, 93, 2066. R. E. Dunmur, M. Murray, R. Schmutzler, and D. Gagnaire, Z. Nururforsch., 1970, 25b, 903.

32

Organophosphorus Chemistry

0 \C-NM~ ,.F* PhN-P,

I

O\

O\C--NMe

I

I P-R I PhNF/ 'F*

I R

F

C-NMe

I

PhN-

IF

'

P, F* F

I1 "C-NMe

I PhN-

I Y-F* Rf

A

"F

C "

-N

I PhN-P,

Me

-

A

I,;F

*

RI F

(W

ON

C-NMe

I

I

Ph N -P.-F

*;

''R

(8b)

attributed to the slowing of those pseudorotations which place both fluorines in equatorial positions. The diazaphosphetidinones (9; R = OMe or NMe,) gave stable phosphoranes (10) with benzil at - 70 "C, but the adduct of (9; R = NMe,) with diacetyl could not be isolated although there was slP n.m.r. evidence for its formation.6

(9)

The bicyclic phosphite (1 1) with ozone gave ' a remarkably stable adduct ( 1 2) which decomposed to form singlet oxygen only above 0 "C. 0

0

0

0

0

(12)

( 1 1)

4 Five-membered A. 2,2'-Bipheny1ylenephosphoranes.--The phosphoranes ( 14) have been from dibiphenylylenephosphonium iodide ( I 3) and the prepared 1v

D. Bernard and R. Burgada, Compt. rend., 1970, 271, C, 418. M.E. Brennan, Chem. Comm.,1970, 956. E. M. Richards and J. C. Tebby, J . Chent. SOC.(C), 1970, 1425.

@riitiqireroimlent Phosphoriis Comporrnds

33

appropriate organolithium reagent in ether. With sodamide in THF the salt (13) gave the aminophosphorane (15) but with N-lithiodiethylamine, i-propyl-lithium, t-butyl-lithium, diphenylmethylsodium, and triphenylmethylsodium, (1 3) gave only the phosphoranyl radical (16).

R

=

BLI,CH:CMe,, CiC-Ru

N

<

Nal\illl ‘I litIIC I I roll

(13

(16)

The phosphoranes (14) readily undergo ligand exchange on treatment with organolithium reagents.l Thus, (14; R = Ph) with butyl-lithium gave an almost quantitative yield of (14; R = Bu) whereas with the less basic methyl-lithium equilibrium was established between (14; R = Ph) and (14; R = Me). The cage-like phosphonium salt (17) with phenyl-lithium in THF gave lo the phosphorane (18) which probably owes its great stability to the relief of strain in the ring structure on changing the bond angle at phosphorus to 90”. For the photolysis of (1 8) see Chapter 10, Section 1.

lo

D. Hellwinkel and H.-J. Wilfinger, Annalen, 1970, 742, 163. T. J. Katz and E. W. Turnblorn, J. Amer. Chem. SOC.,1970, 92, 6701.

34

Organophosphorus Chemistry

B. 1,3,2-Dioxaphospholens.-The kinetics of the addition of trialkyl phosphites to benzil have been investigated spectrophotometrically.ll The second-order reaction of trimethyl phosphite in dioxan has activation paranieters of A H * = 8.4 kcal mo1-l and AS* = - 47.5 e.u. In benzene the rate constant increases linearly with low concentrations of added organic acid and decreases linearly with low concentrations of added base. The Diels-Alder mechanism is considered unlikely on the basis of these data, and the slow step is considered to be nucleophilic addition of the phosphite to the carbon of the carbonyl group (see Scheme).

‘0’L’

‘P

11

Scheme

The pyruvaldehyde and phenylglyoxal adducts (19) with trimethyl phosphite reacted l2 with isocyanates to give the carbamoyl-l,3,2-dioxaphospholens (20), probably as shown. These, with hydrogen chloride, gave phosphate esters of /3-keto-a-hydroxyamides. The isothiocyanate (21) reacted with dienes to give the phosphoranes (22) more rapidly than did the corresponding fluoride and chloride, but less rapidly than did the bromide.13 The rates of reactions of (21) with various dienes were in the order isoprene > butadiene > piperylene > chloroprene. These data support the previous suggestion that attack on the diene is an electrophilic process. The formation of the phosphoranes (23) in the preparation of the phosphonites (24) has been shown l4 to be due to two processes: firstly, the acid-catalysed disproportionation of the phosphonites to give (23) and cyclopolyphosphines; and secondly, the remarkable base-catalysed reaction of the phosphonites with catechol to give (23) and hydrogen. l1 la l3

l4

Y. Ogata and M. Yamashita, J . Amer. Chem. SOC.,1970, 92, 4670. F. Ramirez, J. Bauer, and C. D. Telefus, J. Anier. Chem. SOC.,1970, 92, 6935. N. A. Razumova and F. V. Bagrov, J. Gen. Chem. (U.S.S.R.), 1970, 40, 1232. M. Wieber and W. R. Hoos, Monarsh., 1970, 101, 776.

Quinquecoualent Phosphorus Cornpoitiids

35

(96 - 9 8 O 3

(22)

C. 1,3,2-Oxazaphospholans.-The diastereoisomeric spirophosphoranes (25) and (26) obtained from ( - )-ephedrine and trisdimethylaminophosphine are in equilibrium in benzene their relative proportions varying with temperature. That this equilibration, which requires epimerization at l5

J.-F. Brazier, J. Ferekh, A. Mufioz, and R. Wolf, Compr. rend., 1971, 272, C , 1521

36

Organophosphorus Chemistry

phosphorus, is not due to an intermolecular transfer of ephedrine residues was shown by a study of the diastereoisomers (27) and (28) containing one ( - )-ephedrine and one $-( )-ephedrine.

+

Ph

MeN-P’ I\NMe O d M e

MeN-P’ (“Me

Ph

O A M e

The secondary products formed in the synthesis of spirophosphoranes from trisdimethylaminophosphine and p-amino-alcohols have been identified l6 as the betaines (29), formed from the spirophosphoranes as shown.

A stable adduct (31) has been obtained from the cyclic phosphorodiamidite (30) and benziL6 J. Ferekh, A. Mufioz, J.-F. Brazier, and R. Wolf, Compt. rend., 1971, 272, C, 797.

Quinquecooalent Phosphorus Compounds

+

[:>P*NMe,

37

'(--((

NMe,

N-PJph

Me

PhCO-COPh -+

Me (30)

Ph (31)

D. Miscellaneous.-Low yields of the spirophosphoranes (34) were obtained1' on heating the phosphorane (32) with the aziridines (33). Stable phosphoranes have been obtained from phenanthraquinone monoimine (35) and trialkyl phosphites,18 and from 2-chlorotropone (36) and ~ 1 i d e s . lIn ~ the latter reaction cyanomethylenetriphenylphosphorane gave instead the betaine (37). CH.,.CH,.NH.P(:O)(OR):!

€4

[0,P ,P\ ) +(RO)*P(:0)--N3 0

0

-=[ I

O\ / O 0,p, 0

170'C

(33)

-J

(34) ( 1 9-26%)

(32)

a''+ (35)

Ph,P:CHR

1

--+

0

R

(36)

=

H, Me, C0,Et

CN

(37) N. P. Grechkin and L. N. Grishina, Bull. Acad. Sci. U.S.S.R., 1970, 1549. lUM. M . Sidky and M. F. Zayed, Tetrahedron Letters, 1971, 2313. l 8 1. Kawamoto, Y . Sugimura, and N. Soma, unpublished data quoted in I. Kawamoto, T. Hata, Y . Kishida, and C. Tamura, Tetrahedron Letters, 1971, 2417.

l7

38

Organophosphorus Chemistry

The 1:l-adducts obtained 2o from the ethylene phosphonothioites (38; R = Ph or But) with diacetyl, benzylideneacetylacetone, and phenanthraquinone readily eliminate ethylene sulphide to give the corresponding phosphonate or phosphinate esters. The benzylideneacetylacetone adduct of (38; R = But) contained the two diastereoisomers (39) and (40) which, on elimination of ethylene sulphide at 100 "C,gave isomeric phosphinates.

I

I

H. Ph O......p,~COMe

But'

0

Me

The equilibrium between the conformers (42a) and (42b) of the 1 :1-adduct of dimethyl t-butylphosphonite (41) and benzylideneacetyl-

acetone is so far to one side that the n.m.r. spectrum of the adduct does not vary with temperature.20 The phosphoranes (43) have been obtained from (41), and the corresponding phenylphosphonite, and methylenedeoxybenzoin. In both adducts pseudorotation between (43a) and (43b) became slow on the n.m.r. time scale below - 10 "C.

ButP(OMe),

+

PhCH:C(COMe),

---+

Me0 MeO... I I! Bu'-u;hoMe

(41) MC

(42a) Me0 M e 0... I

Me0

R4T>Ph 0

0

Ph

(43a)

Me0 Bu !.. I ',' P-' PI1 MeO' I

3FoMc Mc

R

=

Ph or But

(43W

A. P. Stewart and S . Trippett, Chem. Comm., 1970, 1279.

Qiririquecovalerit Phosphorits Comportrids

39

A full account has appeared 21 of the reactions of the 2 : 1 fluorenetriet hyl phosphite adducts on heating and with acetonitrile. 5 Six-membered

The bicyclic phosphites (44) and (46) did not react with benzil, even at 60 "C for 20 days.6 With diacetyl at 60 "C for 8 days the l:2-adducts, e.g. (45) from (44), were obtained. The reluctance of these bicyclic phosphites to form stable phosphoranes is remarkable as their geometries appear to be ideal for this purpose. The lH and 19F n.m.r. spectra of the phosphorane (47) indicate rapid positional exchange of the ligands attached to phosphorus.22 This has been quoted 23 as evidence for a (2 + 3)-turnstile process of ligand reorganization, the normal Berry (1 + 4)-pseudorotation being held to be impossible in (47) because of increased strain. Details of this work are awaited with interest .

21

1. J. Borowitz, M. Anschel, and P. D. Readio, J . Org. Chem., 1971, 36, 553.

22

F. Ramirez, S. Pfohl, E. A. Tsolis, I. Ugi, D. Marquarding, P. Gillespie, and P. Hoff-

as

mann, unpublished data quoted in ref. 23. I. Ugi and F. Ramirez, Angew. Chern. Internat. Ecln., 1970, 9, 725.

3 Halogenophosphines and Related Compounds ~~

BY J. A. MILLER

1 Halogenophosphines A comprehensive review of the preparation, reactions, and n.m.r. spectra of phosphorus-fluorine compounds has appeared.l This year's literature has been notable for the first detailed applications of ab initio SCF-MO calculations to the problems of bonding in halogenophosphines and their Comparison of the results of such theoretical calculations with experimental data obtained from photoelectron spectra shows a good correlation in the case of phosphorus trichloride and phosphoryl chloride,2 and of phosphorus trifluoride and its borane c ~ m p l e x . ~ A. Preparation.-Halogen displacement reactions have been used to prepare a number of new aminofluorophosphines. Aminodifluorophosphine ( 1 j has been prepared for the first time, from either bromodifluorophosphine % or chlorodifluorophosphine,6and ammonia. Studies of its n.m.r. spectrum have been made (see Chapter 11). The related NNdifluoroaminodifluorophosphine (2j has been prepared,8 from difluoroiodophosphine, and found to be explosive. Two syntheses of N-alkyl-aminodifluorophosphines have been reported,6* one of which was complicated by the subsequent formation of the phosphorane (3) and the bis-(Nalky1amino)fluorophosphine (4).

a

* 6

7

G . I. Drozd, Russ. Cheni. Rev., 1970, 39, 1. I. H . Hillier and V. R Saunders, Chem. Comm., 1970, 1510. I. H. Hillier, J. C . Marriott, V. R. Saunders, M. J . Ware, D. R. Lloyd, and N. Lynaugh, Chem. Comm., 1970, 1586. D. W. H . Rankin, J . Chem. SUC.( A ) , 1971, 783. J. E. Smith and K. Cohn,J. Amer. C'hem. Suc., 1970, 92, 6185. J . E. Smith, R . Steen, and K . Cohn, J . Amer. Chem. Soc., 1970, 92, 6359. J . S. Harman and D. W. A. Sharp, J . Chem. SOC.( A ) , 1970, 1935.

Halogenophosphines and Related Compounds KNH,

+

PF, --+

RNHPF,

41

+ RAH,.HF,

(3)

t-Butyldifluorophosphine ( 5 ) and di-t-butylfluorophosphine (6) have been prepared from their respective chlorides by different routes,a determined by the ease with which the chloride forms a phosphorane. The mono-t-butyl compound, unlike simple alkyl and aryl a n a l o g ~ e s is , ~stable to disproportionation. Two general routes to 1 -chlorophospholens have been reported,1° and the synthetic utility of these compounds has been developed. Both routes involve the formation of mixtures of 1-chloro-A2-phospholens (7) and 1-chloro-A3-phospholens (8). Grignard reactions of t-pentylmagnesium chloride with phosphorus trichloride have been used I1 to prepare dichloro-t-pentylphosphine (9) and chlorodi-t-pentylphosphine (lo), although the second stage requires more vigorous conditions than the first. RutPCI, 1- SbF, ___> Bu'PF,

Bu',PCI

+

F-

---+

ButzPF

[ , , +) ........-

Ph,P

I

J

PCI3

" lo

+

PetMgC1

PetPCI2

Pe"MgC1

M . Fild and R . Schmutzler, J . Chent. SOC.( A ) , 1970, 2359. H. G . Ang and R. Schmutzler, J . Chem. SOC.,( A ) 1969, 702. D. K. Myers and L. D. Quin, J . Org. Chem., 1971, 36, 1285. P. C. Crofts and D. M . Parker, J . Chem. SOC.(C), 1970, 2529.

Pet,PC1

42

Organophosphorus Chemistry

B. Reactions.-(i) Nucleophilic Attack at Phosphorus. A reinvestigation l2 of the reaction between phosphorus trichloride and t-butylbenzene in the presence of aluminium chloride has shown that the product after hydrolysis is the substituted phosphinic acid (1 l), and not the expected l 3 phosphonic acid (1 2). Bis(N-alky1amino)phosphines have been reported l4 to attack chlorodiphenylphosphine with nitrogen, in the presence of a base, to give bis(N-alkyl-N-dipheny1phosphinoamino)phenylphosphines(1 3). In (1 3), the terminal phosphorus atoms are more reactive14than the central one towards sulphur and towards alkyl halides.

PCI,

(12)

Ph,PCl

-I- PhP(NHR),

EbN ,NRPPh, + PhP, NRPPh,

The product l5 of the base-catalysed reaction between t-butyldichlorophosphine and ethyl alcohol is the expected l6 diethyl t-butylphosphoni te (14), and this quaternizes readily with methyl iodide. An efficient synthesis of carbamic acid halides (1 5 ) , from NN-dialkylformamides, phosphorus trichloride, and thionyl chloride, is reported,” although a full rationalization of the reaction has not been presented. The reactions 18 of phosphorus trichloride with oxetans provide an interesting contrast to those with epoxides, reported several years ago, as shown below. I t appears that the epoxide ring opens at the more highly substituted carbon, to give (16), whereas the comparable oxetan ring opens at the less substituted of the carbon atoms joined to oxygen, to produce (17). A la 13

l4 l6

l6 1’

1’’

R. Brooks and C. A. Bunton, J . Org. Chem., 1970, 35, 2642. G. M. Kosolapoff, J . Amer. Chem. SOC.,1954, 76, 3222. R. Keat, W. Sim, and D. S. Payne, J . Chem. SOC.( A ) , 1970, 2715. P. C . Crofts and D. M . Parker, J . Chem. SOC.(C), 1970, 2342. P. C. Crofts and D. M . Parker, J . Chem. SOC.( C ) , 1970, 332. N . Schindler and W. Ploger, Chem. Bet-., 1971, 104, 969. B. A. Arbuzov, L. Z . Nikonova, 0. N . Nuretdinova, and V. V. Pomazanov, Iire,sr. Akad. Naiik S . S . S . R . , Ser. khirn., 1970, 1426. N. I. Shuikin and I. F. Bel’skii, Zhirr. obshchei. Khint., 1959, 29, 2973.

43

Halogenophosphines and Related Compoundp

possible explanation is that, in the epoxide case, ring-opening precedes carbon-chlorine bond formation, while the same steps in the oxetan reaction are more nearly concerted (see Section 2B). ButP(OEt) (14)

KZNCHO

+

PCl,

+

-

0 II

RZN-C-CI

SOCI,

Me &Me

+

I

PClj --+ Cl,P.O.CH.CH,-CH,CI

Two papers have appeared on the reactions of halogenophosphines with tervalent phosphorus compounds. In a detailed study 2o of the reactions at 20 "C of a range of tertiary phosphines with phosphorus trichloride, dichlorophenylphosphine, and chlorodiphenylphosphine, it has been shown that, in general, 1 : 1 adducts are formed, provided that the tertiary phosphine is a good nucleophile. With diphenylchlorophosphine, for example, an adduct (18) is formed with dimethylphenylphosphine,but not with diphenylmethylphosphine, although the relative importance of steric and electronic factors remains to be established. The related reactions of phosphorus trichloride and of dichlorophenylphosphine are much more complex, and the initial crystalline products are not amenable to analysis. The reactions at 280 "C of a similar system have been shown 21 to lead to halogen exchange, e.g. the conversion of (19) to (20). Ph2PCl

+

20 "C

Me,PPh

2o

F. Kamirez and E. A. Tsolis, J .

a1

K. Sommer, Z . anorg.

Arnpr..

/

Ph2P$MeZPh el

C'hrm. Suc., 1970, 92, 7553.

Chem., 1970, 376, 37.

44

Organophosphorus Chemistry

(ii) Biphilic Reactions with Dienes or Carbonyl Compounds. Stereochemical details have appeared 22 of the reactions between substituted 1,3-dienes and halogenophosphines, such as dichloromethylphosphine (21 a) and dibromophenylphosphine (21 b). In general, both cis- and trans-adducts are formed, and they are not interconvertible via quinquecovalent intermediates. The conversion of these adducts to A3-phospholens or to A3-phospholen- 1-oxides produces cis-trans mixtures. Acetone reacts 23 with neat dichlorophenylphosphine or dichloroethylphosphine to give 3,3,5-trimethyl-A4-1,2-oxaphospholen-2-oxides(22a, b), and other simple methyl ketones have been shown 24 to undergo analogous reactions. Although a rationalization of this process has not been presented, it has been demonstrated 24 that diacetone alcohol with dichloroethylphosphine gives (22b), and that mesityl oxide also reacts 25 similarly with phosphorus trichloride, to give (23). In reactions25 with a number of dichlorophosphines, mesityl oxide forms acyclic products (24), which appear to be the result of ring-opening of the oxides (22), or of their precursors.

<

+

RPX?

(a) R

x

=

=

(b) R = X = (21)

x

CH,, CI Ph Br

Dichloroethylphosphine has been shown 26 to react with methyl vinyl ketone to form 2-ethyl-5-methyl-A4-1,2-oxaphospholen-2-oxide(25), which has been converted to (26) by chlorination in the presence of base. The same phosphine adds2’ to methyl acrylate in the presence of acetic acid to give the phosphine oxide (27). Further exampIes have appeared 28 of the reactions of the phenylhydrazones of methyl ketones with phosphorus trichloride to produce the heterocycles (28). 23 13

24

25

2o

27

**

L. D . Quin and T. P. Barket, J . Amer. Chem. SOC.,1970, 92, 4303. S. Kh. Nurtdinov, V. S. Tsivunin, R. S. Khairullin, V. G . Khashtanova, and Ci. K h . Kamai, Zhur. obshchei. Khim., 1970, 40,36. S. Kh. Nurtdinov, R. S. Khairullin, V. S. Tsivunin, T. V. Zykova, G . Kh. Nurtdinov, and G. Kh. Kamai, Zhur. obshchei Khim., 1970, 40,2377. S. Kh. Nurtdinov, N. V. Dmitrieva, V. S. Tsivunin, and T. V. Zykova, Zhur. obshchei Khim., 1970, 40,2189. A. M. Pudovik, V. K. Khairullin, and R. M. Kondrat’eva, Iziiest. Akad. Nauk S . S . S . R . . Ser. khim., 1970, 2543. V. K. Khairullin, G. V. Dmitrieva, and A. N. Pudovik, Izoest. Akad. Nuuk. S . S . S . R . , Ser. khim., 1970, 871. N . I. Shvetsov-Shilovskii, N. P. Ignatova, and N. N. Mel’nikov, Zhur. obshchei Khim., 1970, 40, 1501.

Halogenophosphines and Related Compounds

45

0

II MeCMe

+

RPCI, OH 0 I I1 Me,C CH,. CMe

-

(a) R

= Ph (b) R = Et

(23) R = C1

+-

EtPCl,

0 II h l e,C =CH C hle

-

0 Me R,II I ,P-CCH

=C(CI)Me

Lle

0

(iii) Miscelkmeoits Renctions. A study 29 of the reactions of halogenoolefins with phosphorus trichloride and oxygen has shown that phosphates [e.g. trans- 1,2-dichloroethylene gives 1,2,2-trichloroethyl phosphorodichloridate, (29)] are the major products. The minor product was identified as the analogous phosphonate (30), which had previously been reported 30 29

so

C . B. C. Boyce and S. B. Webb, J . Chern. Suc. ( C ) , 1971, 1613. L. Z. Soborovskii, Y u . M. Zinov'ev, and J. G. Spiridonova, J . Gen. Chem. ( U . S . S . R . ) , 1959, 29, 1 1 10.

Organophosphorus Chemistry

46

as the only product of this reaction. Phosphorus trichloride and 2-hydroxyethyl phenyl sulphide react 31 to give an 80% yield of the bis-sulphide (31), provided that a base is present. In the absence of base, 2-chloroethyl phenyl sulphide (32) is formed. A complex mixture of products is produced 32 when cyanogen bromide is treated with difluoromethylphosphine (33) at - 20 "C,although the reaction fails when either one of the reagents is replaced, for example, by cyanogen chloride or phosphorus trifluoride, respectively. N.q.r. studies 33 of chlorine compounds have included aryldichlorop hosp h i nes.

P h S . C H , *CH,CI

(33)

hlePF, (33)

+

- ?OCC

BrCN ----+hlcPF4

+

hlcPBr,

+

hlcP(CN),

+

MePBrCN

2 Halogenophosphoranes A. Preparation and Structure.-A study 34 of the i.r. and Raman spectra of t-butyltetrafluorophosphorane (34; n = 1) has indicated that it is a trigonal bipyramid with the t-butyl group equatorial. The preparation 31

ns s3

P. S. Khokhlov, L. A. Kalutskii, Y. A . Nazarov, A. I. Mochalkin, and N. K. Bliznyuk, Zhur. ohshchei Khim.. 1970, 40, 795. R. Foester and K. Cohn, Inorg. Chem., 1970, 9, 1571. J. S. Dewar and M. L. Herr, Tetrahedron, 1971, 27, 2377. R. R. Holmes and M. Fild, Inorg. Chem., 1971, 10, 1109.

Halogenophosphines and Related Compoiinds

47

and n.m.r. spectra of series of t-butylfluorophosphoranes (34; n = 2, 3, or 4) have been described.* For di-t-butyltrifluorophosphorane(34; n = 2), the t-butyl groups are equatorial, and the equatorial fluorine, which has the larger value of Jpp, resonates at higher field than the axial fluorines. The methylfluorophosphines (35a, b) have been prepared 36 and positional exchange between the fluorines has been studied by n.m.r. at different concentrations and temperatures. In the proton n.m.r. of (35b) at low temperatures a doublet of triplets is observed, but at higher temperatures only a doublet is seen, due to the loss of proton-fluorine coupling. This positional exchange does not seem to involve an intramolecular process, such as Berry pseudorotation (which is presumably unfavourable energetically), and possible alternatives are discussed. 2 (b)rt = 3 (35) (a)ii =

A number of preparations of mixed halogenophosphoranes from tervalent phosphorus-fluorine compounds have been reported. For example, acyclic and cyclic fluorine compounds have been converted 36 to phosphoranes, such as (36) and (37), by treatment with chlorine. Similar reactions leading to NN-dialkylaminodichlorodifluorophosphoranes(38) have been described3’ and the stability of (38) to exchange processes commented upon. NN-Dialkylaminotetraiodophosphoranes (39) have been prepared 38 from NN-dialkylaminodichlorophosphinesand lithium iodide, although no detailed physical evidence for the structure of these unusual compounds has yet been reported. The preparation7 of bis(N-alky1amino)difluorophosphoranes (4) has been described above (see Section 1A).

OJ /’\

0,

FC I

M eOPF,CI

(37)

(36)

S

RZNPF2 4- C1,

II

t-- RLNPF,

I<,NPF,CI,

+

C1,

(3s)

I T K,NPCI,

+

LiI

---+

K.,NPI.l

4-

I 1 K , N * P - P -N K 2 , 6 1 . i l

( 39) 311

57

T. A. Furtsch, D. S. Dierdorf, and A. M. Cowley, J. Amer. Chem. SOC.,1970,92, 5759. G . 1. Drozd, M. A. Sokal’skii, and S. Z . Ivin, Zhur. obshchei Khim., 1970, 40,501. G. I. Drozd, M. A. Sokal’skii, 0. G. Strukov, and S. Z. Ivin, Zhiu. nhshchei. Khitii., 1970, 40, 2396.

N. G. Feshchenko, T. V. Kovaleva, and A. V. Kirsanov, Zhur. obshchei Khim., 1970, 40,500.

48

Organophosphorus Chemistry

B. Reactions.-This year has seen the publication of a number of papers on the reactions of olefins and acetylenes with phosphorus pentachloride, to produce new phosphorus-carbon bonds. An investigation sB into the structural requirements of trisubstituted olefins (40)undergoing the above reaction has shown that both steric and electronic factors are important, e.g. an adduct forms with (40; X = CH3) but no reaction occurs for (40; X = Ph). Further examples of the reactions of unsaturated ethers include the formation and decomposition of adducts from a-methoxystyrene (41),*O and from ethyl 2-methylallyl ether (42).41 In general, when these reactions are quenched by sulphur dioxide, the product is a substituted vinylphosphonic dichloride, although the adducts from (41) can be hydrolysed 40 to give p-ketophosphinic acids (43). The formation of f5-chloroalkylphosphonic acids (44) from simple olefins is characterized by only X I

MeC = C H Me

(40) OMe

I PhC=CH,

+

KPCl,

[adduct] so,

/

\ 11.0

(43 1

CH, II

0

II

hlC

I CI,P. CH = C -CHCI I OEt :IR

‘0

V. G. Rozinov, V. V. Mikmnevich, and E. F. Grechkin, Zhrrr. obshchei Khirn., 1970, 40, 935. G. K . Fedorova, Ya. P. Shaturskii, L. S. Moskalevskaya, and A. V. Kirsanov, Zhur. obshchei. Khitn., 1970, 40, 1167. V. V. Kormachev, V. S. Tsivunin, and N. A. Koren, Zhur. obshchei Khirn., 1970, 40, 171 1.

Halogenophosphiiies and Related Compounds

49

moderate yields, and this has been ascribed42 to the competing decomposition of phosphorus pentachloride to phosphorus trichloride and chlorine, and reaction of the latter with the olefin to form 1,2-dichloroalkanes (45). By the addition of two moles of phosphorus trichloride to the reaction mixture, the generation of chlorine has been inhibited, and the phosphonic acids (44) have been isolated 42 in over 90% yield (e.g. using oct- 1-ene.) PCI,,

PCI,

PCI,

+

CI,

I/ (H*),P. CCI,.&IiR

R CHCI CH, C I

(44)

(45)

The stereochemistry of the addition of phosphorus pentachloride to isolated acetylenes in non-polar solvents has been shown 43 by n.m.r. to be cis, as illustrated for the adduct (46) from propyne. This observation has been explained in terms of a four-centre process. Contrary to a previous report,44the reaction 46 of triphenylphosphine hydrobromide with phenylacetylene carboxylic acid (47) yields both the trans- and the known44 cis-adducts.

+

P tl{I’, 1% 42

43 44

,c=c,

,co2 I r Rr-

H

Y . Okamoto and H. Sakurai, Bull. Chem. SOC.Japan, 1970, 43, 2613. A. V. Dogadina, B. I. Ionin, K. S. Mingaleva, and A. A. Petrov, Zhur. obshchei Khini., 1970, 40, 2341. H . Hoffmann and H. J. Diehr, Chem. Ber., 1965, 98, 363.

Organophosphorus Chemistry

50

A reinvestigation l 6 of the reaction p7 of acetals with phosphorus pentachloride has shown that the intermediate adducts give products whose structure is dependent upon the conditions of work-up, as shown below for the formation of (48) and (49). The formation48 of vicinal dihalides from epoxides and triphenylphosphine dichloride (50a) or di bromide (50b) has been studied in detail. With styrene epoxide, the only detectable intermediate was the salt (51), most probably formed as a result of epoxide ring opening to give the more stable carbonium ion, followed by trapping with chloride ion [cf. formation of (16), see Section 1B (i)]. When cyclohexene epoxide was similarly allowed to react, the resultant vicinal dihalide was a mixture of cis- and trans-isomers, and the authors suggest that the latter is formed by halogen participation in the breakdown of the intermediate (52). Me CH (0R) SO,

+

+[adduct] --+

PC15 0

+

(48)

0 II CllP. C € I=C € i ( O R )

I.

(48)

I1

CI,P*C=CH(OR) I C1

(49)

0

/ \

45 40

+

Ph,PX2 - + (a) X = C1 (b)X = Rr

I I KCH-CHR

+

Ph,P=O

E. E. Schweizer and A . T. Wehman, J . Chrm. SOC.( C ) , 1970, 1901. V. V. Moskva, V. M. Ismailov, and A. I. Razumov, Zhur. obshchei Khitti., 1970, 40,

1489.

V. V . Moskva, V. M. Ismailov, and A . 1. Razumov, Zhur. obshchei Khim., 1968, 38, 2587. IH

A. N. Thakore, P. Pope, and A . C. Oehlschlager, Tetrahedron, 1971, 27, 2617.

Halogenophosphines and Related Compounds

51

a::

The dehalogenation of cyclic trihalogenophosphoranes of general formula (53) with triphenylphosphine has been used lo*4@ in the preparation of 1-halogenophospholenes (see Section 1A). Grignard reagents reduce 6 0 the complex (54), formed from triphenylphosphine oxide and phosphorus pentachloride, to give phosphines. A series of reactions between o-phenylenedioxybis(trimethy1silane) ( 5 5 ) and various tri- and tetra-fluorophosphoranes has been described.61 The products are oxyphosphoranes, such as (56) and (57), the latter representing an unprecedented cleavage of axial fluorines from a difluorophosphorane with this type of silicon compound. Reports of further studies62of the reactions of fluoride ion with fluorophosphoranes have included the reactions of trifluorophosphoranes, such as (58).

Ph,$OPCI,

-I- RMgX

---+

Ph,P

+

R,P

(55)

o-"'

PRu3

/

0 '

(57) I0

P. Coggon, J . F. Engel, A. T. McPhail, and L. D. Quin, J . Ariier. Chern. Sor., 1970, 92, 5778.

62

B. V. Timokhim, E. F. Grechkin, and A . V. Kalabina, Zhur. obshchei Khirn., 1970, 40, 2133. G. 0. Doak and R. Schmutzler, J . Chern. Soc. ( A ) , 1971, 1295. S. C. Peake, M. J. C. Henson, and R. Schmutzler, J . Chem. SOC.( A ) , 1970, 2364.

52

Organophosphorus Chemistry RPArF,

+ 6

+ RPArF,

(58)

The reactions of phosphorus pentachloride and diphenyltrichlorophosphorane with amines and related compounds are reported in Chapter 9. The n.m.r. spectra of phosphine-phosphorus pentafluoride adducts have been described 53 (see Chapter 11 for details). 3 Phosphines containing a P-X Bond (X = Si, Ge, or Sn) The ynthesis of alkyl(phenyl)trimethylsilylphosphines (59a, b) and the results of an n.m.r. study of their inversion have been reportede5*The inversion of these compounds has a AG barrier of 19 kcal mol-l, and a comparison of this value with that of methylphenyl-t-butylphosphine(60), which is known to be about 33 kcal mol-1 at 130 "C,has been made. These data have been discussed in terms of a facilitation of inversion by the d-orbitals of silicon. Phenylphosphine and its derivatives have been shown65to react with the dichloro-compounds (61) in which the central atom varies, as shown below. /

R' PI1 -P,

PhP,

/

Me

But (60)

SiMe2R2 (a) R 1 = Pr', R2 = Me ( b ) R 1 = Me, R2 = Ph (59)

A = Sn M

cyclic trimers

Treatment of diethyl(triethylgermy1)phosphine (62) with carbonyl compounds results 56 in cleavage of the phosphorus-germanium bond, although the isolated products are highly dependent upon the structure of 63 G4 G5

C. W. Schultz and R . W. Rudolph, J . Amer. Chem. Soc., 1971, 93, 1898. R. D. Baechler and K. Mislow, J . Atner. Chem. SOC.,1970, 92, 4758. H. Schumann and H . Benda, Chem. Ber., 1971, 104, 3 3 3 .

53

Malogenophosphines and Related Compounds

the aldehyde or ketone used. Some examples are given below. The thermal decomposition of the bis-phosphine (63), in the presence of mercury, gives 57 an unusual product, which is tentatively assigned a cage-like structure. An extension of the reactions of lithium tetraphosphinoThis is aluminate (64) to the synthesis of stannylphosphines is illustrated by the preparation of trimethylstannylphosphine (65) in 68% yield.

R I

Et,P.CH.OGeEt,

L CI,CI1=0

Et,PCHO

+

Et,GeCl

+ [cl,c:l

Me,Ge(PH,),

56

67 5B

J. SatgB, C. Couret, and J. Escudj6, J . Organonietallic Chem., 1970, 24, 633. A. R. Dahl and A. D. Norman, J . Amer. Chem. SOC.,1970, 92, 5525. A. D. Norman, J. Organoinetallic Chem., 1971, 28, 81.

3

4 Phosphine Oxides and Sulphides BY J. A. MILLER

This year’s literature has been characterized by an increasing number of papers devoted to theoretical studies of the bonding in phosphine oxides and related compounds, and these are discussed in Section 1. The chemical aspects of phosphine oxides have not shown any major new developments over the past year, and, once again, these have been sub-divided into sections on the preparation and on the reactions of phosphine oxides.

1 Bonding and Structure Several groups 1-3 have applied self-consistent field molecular orbital (SCF-MO) calculations to phosphine oxide (la), although this compound has yet to be prepared. From these calculations, it is clear that (la) is predicted to derive considerable stabilization from participation of the d-orbitals of phosphorus in the bonding to oxygen. This n-back-donation is much less important in the phosphine-borane complex (2a).2 Comparable calculations o n trimethylphosphine oxide (1 b) indicate that it has a higher binding energy and dipole moment than (la), which may partly explain the failure of attempts to synthesise the latter. The bonding in phosphorus oxyfluoride ( I c) has also been investigated by SCF-MO calculation, and has been compared with that in trifluorophosphineborane (2b) and in the isoelectronic oxides (3) and (4).5 Once again, the d-orbital participation is greater in the oxide than in the borane complex, and there is a marked decrease in the molecular energy of the oxide when d-orbital contributions to the bonding are included. The photoelectron spectrum of

*

H. Marsrnann, L. C. D. Groenweghe, L. J. Schaad, and J. R. Van Wazcr, J. Atner. Chent. SOC.,1970, 92, 6107. J. Demuynck and A. Veillard, Cheni, Conint., 1970, 873. I. H. Hillier and V. R. Saunders, J. Chern. Sor. ( A ) , 1970, 2475. 1. H. Hillier and V. R. Saunders, J. Chern. Soc. ( A ) . 1971, 664. I. H. tlillicr and V. R. Saunders, Cfieni. Corrim., 1970, 1183.

Pliosphitie Oxides mid Siilphides

55

(lc) has been studied,6 and this also indicates that d-orbitals are important in its bonding. X-Ray structure determinations (see Chapter 11 for details) have been reported for triphenylphosphine oxide,' tri-o-tolylphosphine oxide,8 sulphide,* and selenide,8 and for cis-2,2,3,4,4-pentamethyl-l-phenylphosphetan-1 -oxide ( 5 ) . 8 Electron spectroscopic studies lo of phosphorus oxychloride and thiophosphoryl chloride in the gaseous state, and 31P n.ni.r., i.r., and U.V. spectra of phosphine sulphides l1 have appeared. Dipole moments have been used12 to define the stereochemistry of 2-cyanoethylphosphine oxides, such as (6), which is shown in its preferred conformat ion.

2 Preparation

A. Using Organometallic Reagents.-The displacement of a1koxy-groups from phosphinate esters by alkyl-lithium reagents has been used in the preparation l 3 of diastereomerically enriched tertiary phosphine oxides, such as (7), from menthyl phosphinates. A similar reaction l 4 of a number of enol diphenylphosphinates, e.g. (8), leads to the production of an enolate anion, which can be trapped efficiently by alkylation. The heterocyclic rings of the 1,2-oxa-A3-phospholen-2-oxides (9a, b) open l5 with phenylmagnesium bromide to give phosphine oxides, although (9b) also undergoes a conjugate addition reaction to the double bond. No indication is given of the sequence of displacement and addition reactions in the reaction of (9b). The oxides (10) can be metalated and alkylated, or can be treated with Grignard reagents as illustrated.

' lo l1 l2

l3

D. C. Frost, F. G . Herring, K . A. R . Mitchell, and I. A. Stenhouse, J . Amer. Chem. SOC.,1971, 93, 1596. G. Bandoli, G. Bortolozzo, D. A. Clemente, U . Croatto, and C. Panattoni, J . Chem. SOC. (A), 1970, 2778. T. A. Shaw, M. Woods, T. S. Cameron, and B. Dahlen. Chern. a d Ind., 1971, 1 5 1 . Mazhar-ul-Haque, J . Chem. SOC.( B ) , 1971, 117. T. Moritani, K . Kuchitsu, and Y. Morino, Inorg. Chem., 1971, 10, 344. H . Goetz, M. Hadamik, and H. Juds, Annulen, 1970, 742, 59. E. A. Ishmaeva, A. N. Pudovik, and A. N. Vereshchagin, Izrvst. Akad. Nauk S . S . S . R . , Ser. khim., 1970, 2790. W. B. Farnham, R. K. Murray, and K . Mislow, J . Amer. Chem. SOC., 1970, 92, 5809.

l4

I . J. Borowitz, E. W. R . Casper, and R. K. Crouch, Terrnhedron Letters, 1971, 105. I . G. M. Campbell and S. M. Raza, J . Chem. Sor. (0,1971, 1836. L. Mnier, ffelrr. Chim. Acta, 1970, 53, 1948.

56

Organophosphorus Chemistry

P 11

Me

CHPh II C Ph’ ‘0-PPh,

McLi

0 0 II II PhCCHPh +Ph,PMc

R I

PhC CH Ph II 0

R

0 0ti II I Ph2PC( Me)= CHC HPh

A

(b) R

=

Ph

(9)

Grignard reactions have been used l7 in the preparation of 1-(dialkylphosphinyl)-l,3-dienes, e.g. ( 1 l ) , which are intermediates in the synthesis of antiflame polymers. Double-resonance n.m.r. techniques have been applied l 8 to the study of the reactions between thiophosphoryl halides and Grignard reagents. For example, the reaction between methylmagnesium iodide and t-butyldibromophosphine sulphide gave the mixed

I*

L. N. Mashlyakovskii, B. I. Ionin, 1. S. Okhrimenko, and A. A . Pctrov, Zhrrr. ohshchei Khitri., 1970, 40, 804. G. Hagele and W. Kuchen, Chettt. Ber., 1970, 103, 2885.

Phsphiiie Oxides crnd Srtiphides

57

sulphides (12) and (13) as major products, and these were analysed by the above method. The synthesis of silver (or mercury) derivatives of a-diazoalkyldiphenylphosphine oxide (1 4) has been reported.lfi

0

n

L I

0

11'1

( i i ) NaNO,

-

(iii) AgO(Hg0)

€1

,

.

"L'

(14)

B. By Hydrolysis Reactions.-Details have appeared 2o of the synthesis of dibenzophosphorin oxides 21 (1 5 ) from 5-alkyldibenzophospholes, by reaction with methyl propiolate in the presence of water, and of confirmatory syntheses from phosphinic acid chlorides, as shown below. Evidence for the suggested mechanisni of the ring-expansion reaction is presented. The hydrolysis of enamine phosphine oxides is an efficient, although somewhat indirect, method for the preparation 2 2 of /%ketoalkylphosphine oxides (16) [see Section 3(iii), for the preparation of enamine oxides]. Reasonable yields (48-66%) of trialkylphosphine oxides (1 7) have been obtained 23 by the alkaline hydrolysis of the products from the pyrolysis at 220 "C of red phosphorus with alkyl halides, in the presence of iodine. The preparation of diphenylphosphine oxide normally 24 involves the controlled hydrolysis of chlorodiphenylphosphine,but the product has a significant amount of diphenylphosphinic acid impurity, This problem 1D

20

ai aa as 24

M. Rcgitz, A. Liedhegener, U. Eckstein, M. Martin, and W. Anschutz, Annaleti, 1971, 748, 207. E. M. Richards and J. C. Tebby, J . Chem. SOC.( C ) , 1971, 1064, E. M. Richards and J. C. Tebby, Chem. Comm., 1967, 957. N. A. Portnoy, C. J . Morrow, M. S . Chattha, J . C. Williams, and A. M. Aguiar, Tetrahedron Letters, 1971, 1397. N. G. Feshchenko, A. A. Koval, and A. V. Kirsanov, Zhur. obshrhei Khim., 1970, 40, 2385. G. I. Derkach and A. V. Kirsanov, Zhur. obshchei. Khitn., 1959, 29, 1815.

\

-i Oli

F-KO,hl c

4 /

0

CI

Phosphorus -t R1

+ T,

'20

c R 11

R,P=O = C,,li.,,, I = 6-10

,

(17)

can now be overcome25 by vacuum sublimation of the crude oxide. Bisphosphines (18) can be converted 28 to their oxides by hydrolysis of the complexes formed by the dissolution of (1 8) in phosphorus oxychloride. Difluorophosphine oxide (19) has been prepared 27 in good yield by the treatment of phosphorus tribromide with zinc fluoride, in the presence of water, or of phosphorous acid. 26

27

H . J . Brass, R . A. DiPrete, J. 0. Edwards, R. G. Lawler, R . Curci, and G . Modena, Tetrahedron, 1970, 26, 4555. E. Lindner and H. Beer, Chent. Ber., 1970, 103, 2802. E.-A. Dietz and R. W. Parry, Inorg. Chent., 1971, 10, 1319.

Phospliiiie Oxides aird Sulphides

59

i

I I,O

I< L’ I’ (0)(C H, ),,P (O)K,

C. By Oxidation. --This year’s literature has been notable for attempts to study the details of certain phosphine oxidation reactions. In one such investigation 28 nitric acid was found to oxidize phosphines, or phosphine sulphides, to phosphine oxides with inversion of configuration at phosphorus, whereas dinitrogen tetroxide, in the absence of acid, was found to oxidize the same compounds with predominant retention. The partial racemization observed with the latter reagent was probably due to the racemization of the oxides, since methylphenyl-n-propylphosphineoxide (20) was shown independently to racemize fully on prolonged treatment with dinitrogen tetroxide. The stereochemical aspects of these reactions are summarized below, using (20) and its derivatives. MC

hl c

M,C

(20) (S)

”1 The anaerobic oxidation of phosphines to their oxides by hydroxide ion has been shown 29 to involve the liberation of hydrogen, possibly from the intermediate (21). These oxidations were studied with water-soluble phosphines, since solubility was found to be the main factor controlling the rate of oxidation. The p r e p a r a t i ~ n and , ~ ~ detailed n.m.r. spectrum, of PP-dimethyl-P’P’-diphenyldiphosphinedisulphide (22) is a relatively rare example of a study of a mixed disulphide. Many examples of routine oxidation of phosphines to their oxides have appeared. These include the preparation of polyhalogenoarylphosphine oxides using dichromate yu

3u

J. Michalski, A. Okruszek, and W. Stec, Chem. Comm., 1970, 1495. S. M. Bloom, S. A. Buckler, R. F. Lambert, and E. V. Merry, Chem. Comm., 1970,870. J. Koketsu, M. Okamura, Y.Ismii, K . Goto. and S. Shimizu, Inorg. Nuclear Chem. Letters, 1971, 6 , 15.

Organophosphorus Chemistry

60

oxidation,31of the bisphosphine oxide (23) by peracetic acid ~ x i d a t i o nof ,~~ triphenylphosphine oxide with a ruthenium complex (24) as of the bicyclic phosphine oxides (25) by hydrogen of the tertiary phosphine oxides (26) and (27) with chlorine,35and of the sugar diphenylphosphine oxides (28) and (29) by aerial oxidation.96

PI,, -r -CH?

0-ch2

I

t-I

O=PPh, (28) 31 s2

33

S. S. Dua, R. C. Edmondson, and H. Gilman, J . OrganomefafficChem., 1970, 24, 703. K. G . Weinberg and E. B. Wipple, J . Amer. Chem. SOC.,1971, 93, 1802. B. W. Graham, K . R. Laing, C. J . O’Connor, and W. R. Roper, Chem. Comrn., 1970, 1272.

ss 36

(29)

Y. Kashman and 0. Awerbouch, Tetrahedron, 1970, 26, 4213. L. Maier, Helv. Chim. Acra, 1970, 53, 2069. L. 0. Hall and P. R. Steiner, Chem. Comnr., 1971, 84.

Phosphine Oxides and Sulphides

61

D. Miscellaneous.-A further study 37 of the reactions of diphenylphosphine oxide with tetracyclone has confirmed 38 that the reaction yields the oxide (30) under miId, basic conditions, and that the reaction is thermally reversible. The displacement of halogen from phosphorus by aminocompounds has been used in the synthesis of a number of aminofluorophosphine oxides (3 1),39 and of N-methyl-NN-bis(dichlorophosphiny1)amine (32).40

POCl,

+ hle,SiNSiMc,

3 Reactions A. Nucleophilic Reactions of the P=O Group.-Tris(trifluoromethy1)phosphine oxide (33) reacts 41 with hexamethyldisiloxane to give a phosphorane, whose n.m.r. spectrum at - 140 “C shows non-equivalent trifluoromethyl groups. Although this unusual reaction clearly involves nucleophilic attack of the phosphoryl oxygen on silicon at some stage of the reaction, a full study of the mechanism has not been published. Tertiary phosphine oxides can be converted 4 2 cleanly into dichlorophosphoranes (34) by treatment with two moles of phosphorus pentachloride. Alkylation of the sodium salt of tetraphenylmethylenediphosphinedioxide (35) with alkyl halides, in dimethyl sulphoxide, has been reported43 to M. J. Gallacher and I. D. Jenkins, J . Chem. SOC.( C ) , 1971, 210. J. A. Miller, Tetrahedron Leffers, 1969, 4335. H. W. Roesky and W. Kloker, Z . anorg. Chem., 1970, 375, 140. 4 0 R. Keat, J . Chem. SOC.( A ) , 1970, 2732. a R. G. Cave11 and R. D. Leary, Chem. Cotnnz., 1970, 1520. la M. I. Zola, L. P. Zhuravleva, and A. V. Kirsanov, Zhur. obshchei Khim., 1970,40, 1957. Yu. M. Polikarpov, K. Zh. Kulumbetova, T. Ya. Medved, and M . I. Kabachnik, Izuest. Akad. Nauk S.S.S.R., Ser. khitn., 1970, 1326.

37

38

Organophosphorus Chemistry

62

result in the formation of 0-alkylated products, as suggested by their hydrolysis to alkyl diphenylphosphinates and methyldiphenylphosphine oxide. (CF,,):,I’=O

+- (hlc,,Si ).O (33)

-*

(CF,),P(OSihlc,),

(35)

B. Electrophilic Reactions of the P=O and P=S Groups.- Hydrolysis studies with phosphine oxides continue to reveal problems associated with the role of pseudorotational processes in determining mechanism. The failure of benzyldiphenylphosphine oxide (36) to exchange l80when hydrolysed in H,180 under bimolecular conditions has been r e p ~ r t e d . ~ * This has been interpreted in terms of an intermediate which breaks down very rapidly to give the observed products, and possible explanations have been discussed. Hydrolysis of the phosphetan-1-oxides (37a, b) results in predominant ring-cleavage, or ring-retention, according to the nature of R.45By comparison with the results from other cyclic systems, it is clear that, in general, both the ring-size and the stabilities of the potential leaving groups are important in determining the reaction products. 0

IRO

II l’t, ~ ’ I ~ ~ I ~ C*~WI II ~- --+ P I ~ PI~,P-O

+

+ cIr:{iitl

P. Haake and G. W. Allen, Tetrcihedrnti Lctlers, 1970, 31 13. B. R. Ezzell, J . Org. Chem., 1970, 35,2426.

Pliospitinc Oxides and Sulphides

63

Dimethyltrichloromethylphosphine oxide (38) is hydrolysed 46 in alcoholic alkali to give ethyl dimethylphosphinate. A kinetic study4’ of the catalysis by hydroxide ion of the oxidation of diarylphosphine oxides by perbenzoic acids has shown that the peracid anion is involved in nucleophilic attack at phosphorus in the rate-determining step. A pentacovalent intermediate (39) is suggested for these oxidations. The desulphurization of triarylphosphine sulphides (40) by aryl-lithium reagents has been reinvestigated** and shown to involve attack at phosphorus, and not at Evidence for this view includes the partial scrambling of aryl groups (attached to phosphorus) by aryl-lithium treatment of triphenylphosphine sulphide, and the ring opening of the phosphetan-1-sulphide (41) under similar conditions, as shown. 0

II

0

Mc,PCCI, 0

II

ArJ’II

+ EtOH

(38) 0 II

-011

11 hlc,I’OEt

+ CHCI,

-0

__

+ Ar’COU

.Oil

0

I

II Ar,l’-O.O.CAr’ I 11

(39) /-“Il

-0

I Ar,I’=O

+

0 II -0-CAr‘

I I

J.

hIc,C (Ph) CH( hlc) c hlC,PPll2

47 48

48

N. M. Mel’nikov, K . 0. Shvetsova-Shilovskaya, and I. L. Bogatyrev, Zhur. obshchei Khim., 1970, 40, 1650. R. Curci and G. Modena, Tetrahedron, 1970, 26, 4189. J. R. Corfield and S. Trippett, J . Chem. SOC.( C ) , 1971, 334. G. Wittig and H. J . Christau, Bull. SOC.chim. France, 1969, 1293.

64

Organophosphorus Chemistry

Two contrasting conclusions have been reported in the reactions of lithium aluminium hydride in THF with phosphine oxides and phosphine sulphides respectively. The secondary oxide, phenyl-a-phenylethylphosphine oxide (42), has been found 5 0 to be racemized very rapidly by lithium aluminium hydride, and this observation casts some doubt on earlier reports 5 2 of the preparation of optically active secondary oxides by reduction of menthyl phosphinates with this reagent. A similar study of the treatment of (R)-( )-methyl-n-propylphenylphosphinesulphide (43) with lithium aluminium hydride has revealed 5 3 no racemization. These results have been rationalized on the basis of the preferred site of attack of hydride on the complexed intermediate (44), which, in the case of phosphine oxides (X = 0), is at phosphorus, and in the case of the sulphides (X = S), is at sulphur. Such behaviour is comparable to that observed during the reduction of phosphine oxides and sulphides with hexachl~rodisilane.~~~ 55 519

+

C. Reactions not involving P=O or P=S Groups.---Enamhe phosphine oxides (45) have been prepared22 by the addition of amines to l-alkynyiphosphine oxides, and the reactions of their anions with various electrophiles have been 57 With ketones 56 a Wittig-type reaction leads to the formation of @-unsaturated ketones, in 53-70x yield, while with epoxides 5 7 cyclopropyl ketimines are formed. A Diels-Alder reaction of l-phenyl-A*-phospholen-I -oxide (46) with 1,4-diacetoxybutadiene has been used 5 * in the preparation of 1-phenyl-benzo[h]phosphole (47), as W. 9. Farnharn, R. A . Lewis, R . K . Murray, and K. Mislow, J . Amer. Chem. Sor.., 61

63 64

66

6e

67

1970,92, 5808. T. L. Emrnick and R. L. Letsinger, J . Airier. Chem. SOC.,1968, 90, 3459. 0. Cervinka, 0. Belovsky, and M . Hepnerova, Chem. Comrn., 1970, 562. R. Luckenbach, Tetrnhedron Letters, 1971, 2177. K. Naumann, G. Zon, and K . Mislow, J . Amer. Chern. Sac., 1969, 91, 7012. G. Zon, K . E. Debruin, K . Naumann, and K . Mislow, J . Arner. Cherit. Soc., 1969, 91, 7023. N. A . Portnoy, C. J. Morros, M. S. Chattma, J. C. Williams, and A . M. Aguiar, Tetrahedron Letters, 197 1 , 1401 . N. A . Portnoy, K . S. Yong, and A . M . Aguiar, Tetrcihedron Letters, 1971, 2559. T. M. Chan and L. T. L. Wong, Curiud. J . Chern., 1971, 49, 530.

65

Phosphinc Oxides mid Sulphiiies

outlined. Thc unusual phosphine oxide (48) has been prepared6@by irradiation of the bicyclic phosphine (49), and an intermediate tricyclic oxide can be isolated if acetone is omitted from the photolysis.

0 PI7 \/

0 Ph

0 Pi1 \/

\/ 1’

iw

ill^

;:B

T. J. Katz, J. C. Carnahan, G . M. Clarke, and M. Acton, J . Amer. Chem. SOC., 1970, 92, 134.

66

Organophosphorus Chemistry

The preparation 6o of 3,4,5-triphenyl-4-phosphabicycIo[3,1 ,O]hex-2-ene4-oxide (50), by hydrolysis of the salt (Sl), is believed to involve a 1,3migration of the iodomethyl group of (50), since the oxide (52) has been isolated as an intermediate. Photolysis or pyrolysis of (50),or of the oxide (53), yieldss1 a dimeric substance, to which structure (54)has been tentatively assigned. The photolysis of the phosphetan-1-oxides (55) and (56) has been shown 6 2 to yield products arising from both ring-expansion and ring-cleavage processes. In the case of the oxide (56), there was no preference for migration of either the primary or tertiary ring carbon to form the ring-expanded products.

(53)

1’11

82

1I

PI1

A. N. Hughes and C. Srivanavit, Canad. J . Chem., 1971,49, 879. A. N . Hughes and C. Srivanavit, Canad. J . Chem., 1971, 49, 8741. M . J . P. Harger, Chem. Comnr., 1971, 442.

Phosphirre Oxides and Sulphides

67

13;,;

Deamination reactions of (2-amino- 1,l -dimethyl)ethyldiphenylphosphine oxide (57) result 63 in the formation of three products, in each of which the diphenylphosphinyl group has migrated to the primary carbon of the starting material. These reactions are unusual examples of non-assisted migration of a phosphinyl group. The application 84 of p-(diphenylphosphinyI)benzenesulphonic acid (58) to the synthesis of esters of amino-acids has made the work-up much simpler, since the resultant oxide is water-soluble. Diphenylphosphinyl isocyanate (59) can be prepared 65 from diphenylphosphinic amide.

0

il

0 -

T’t~21’-Nl-~

84

O6

/I

+ CI--<‘--Cl

0

II

-+ Ph,I’N=C-O

(59) P. F. Cann and S. G. Warren, Chern. Comm., 1970, 1026. T. Mukaiyama, K . Goto, R. Matsueda, and M. Veki, Tetrahedron Letters, 1970, 5293. G. Tomaschewski and B. Rreitfield, J . prnkt. Chetn., 1969, 311, 256.

3 Tervalent Phosphorus Acids BY B. J. WALKER

1 Introduction Again it has been necessary to operate a policy of selection in preparing this chapter and, in general, unless it has some novelty, purely preparative work has been ignored.

2 Phosphorous Acid and its Derivatives A. Nucleophilic Reactions.-(i) Attack on Saturated Carbon. The Arbusov reaction has been used to prepare organosilicon-substituted phosphonates (1)’ and phosphorylated ethers (2a) and sulphides (2b).2 Bromo- and chloro-derivatives of the cyclic phosphite (3) do not react with ethyl halides RP(OEt)?

+ EtOSiMe,CH,CI

0 11 c>RPCH,Si(OEt)Me, I

4 11 140

to give Arbusov p r o d ~ c t s although ,~ reaction does occur with the corresponding fluoro-compound. This is explained in terms of back donation from fluorine lone pairs to phosphorus d-orbitals, thus enhancing the nucleophilicity of the phosphorus. E. F. Bugerenko, A. S. Petukhova, and E. A. Chernyshev, J. Gen. Chem. (U.S.S.R.), 1970, 40,579.

* H. Gross and H. Seibt, J.prakt. Chem., 1970,312,475 (Chem. A h . , 1970,73, 109 851m). a

N. A. Razumova, Zh. L. Evtikhov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1970, 40, 911.

Terualent Phorphorus Acids

69

The mechanism of the Arbusov reaction has been the subject of some study. Intermediates (4), isolated at low temperatures from the reaction of phosphonites with alkyl halides, show 31Pn.m.r. chemical shifts in the region of - 95 p.p.m. in a wide variety of solvent^.^ RP(OR’)2

+ Me1

-

RMe$(OR’), I(4)

This suggests a large degree of positive charge on phosphorus and so an ionic, rather than a quinquecovalent, structure. Bodkin and Simpson have investigated the stereochemistry of the Arbusov reaction with cis and trans cyclic phosphites (5).6 Some ring opening was observed but the main product is the cyclic phosphonate (6). The reaction shows very low stereospecificity, in contrast to the result expected from the normally accepted mechanism (7) which would give a retained phosphorus conOR

0 R1

I

o’p,

\. /.

0

+RII--+

o/p\ I

c

?

+RI

0

0 CPh,

\*/

figuration. In this important communication the authors suggest that stereochemistry is scrambled through a quinquecovalent intermediate with a sufficient lifetime to allow pseudorotation (see Chapter 2). Reaction of the phosphite ( 5 ) with trityl fluoroborate gives a salt, which on decomposition with iodide can give tritylphosphonate (8) completely stereospecifically. This system presumably acts as a model of the presently accepted mechanism (7) for the Arbusov reaction. In view of these results a new mechanism is suggested with initial reversible formation of a quinquecovalent intermediate (9), followed by

5

A. I. Razumova, B. G . Liorber, T. V. Zykova, and I. Ya. Bambushek, J . Gen. Chern. (U.S.S.R.), 1970, 40, 1996. C . L. Bodkin and P. Simpson, Chern. Comm., 1970, 1579.

Organophosphorus Chemistry

70

decomposition of its ionic equivalent. The reversibility of the formation of (9) is evidenced by the partial isomerization of phosphite obtained from incomplete reactions.

K'

OR I

RO, I ,I L

ONP'O

An earlier report that diethyl t-butylphosphonite (10) did not undergo an Arbusov reaction, presumably for steric reasons, has been withdrawn since the presumed phosphonite is now shown to be the phosphonate. Trippett and Stewart have showne that the phosphonium salts (11) derived from the reaction of phenyl di-t-butylphosphinite (12) with alkyf halides are highly resistant to hydrolysis and they suggest that this is due to the reluctance of phosphorus to accommodate two t-butyl groups in a trigonal-bipyramidal intermediate. Russian workers have shown that alkylation of the P'" derivatives ( I 3) with triethyloxonium fluoroborate takes place at phosphorus rather than @

ButP(OEt), (10)

PhOP(But),

+ RI -+

PhO6R But

(12)

(]

I-

1)

RnP(S R1)3-n

(13) sulphur, although this tendency decreases with decreasing n. The site of alkylation was determined from 31 P n.m.r. chemical shifts and explained in terms of phosphorus lone pair-sulphur d-orbital interactions. P. C. Crofts and D. M. Parker, J . Chem. SOC.( C ) , 1970, 332. P. C. Crofts and D. M. Parker, J . Cheni. Soc. ( C ) , 1970, 2342. S. Trippett and A. P. Stewart, J . Chem. SOC.( C ) , 1970, 1263. E. A . Krasil'nikova, T. V. Zykova, A . I. Razumova, and N. I. Sinitsyna, J . Ceti. Chrrn. (U.S.S.R.), 1970, 40, 2144.

Tervalent Phosphorirs Acids

71

Group 1V substituted phosphinite (14) lo and phosphite (15) l 1 esters have been prepared by the reaction of dialkylphosphinite anions with Group IV halides and amines. R,MX

-

+ R',P-O

W

K'.,P--O-MK:,

-

X M

= =

(14)

Cl. NR', Si. Ge, Sn

(15)

Dialkyl dimethyl phosphoramidites (16) react with /3-propiolactone to give the phosphoramidate (17) and the phosphonate (18).12 A kinetic study suggests a mechanism involving initial attack of phosphorus at saturated carbon to give (17), while a four-centred transition state (19) is invoked to explain the formation of (1 8).

+

Me,NP(OR),

CO--0

I I CH,-CH,

-+

0 II ROP-NMc,

I

C H,.CH,-CO-O R

(16)

(17)

0 I1 Mc,N---C-CH, .

.

RO),I;-O--LH, (19)

+

0

II

( RO)ZP.CH,*CH,*CO*NMc,

(18)

(ii) Attack on Unsaturated Carbon. The addition of dialkyl phosphites to a,P-unsaturated amides (20), followed by Hofmann degradation, has been used to prepare the naturally occurring 2-aminoethylphosphonic acid (21).13 Acrylic acid reacts with the cyclic phosphite (22) to give the ninemembered ring phosphonate (24).14 1.r. studies of the reaction indicate that an intermediate (23) is involved and a mechanism is suggested which, although not unreasonable, is rather complex and contains several steps which at present do not have direct analogies in the literature. N-Acyl salts of nitrogen heterocycles phosphorylate in the hetero-ring, rather than at the carbonyl group, to give, for example, (25).16 The addition of dialkyl phosphites to ynamines has been reported.16 The products lo

I4

K. Issleib and B. Walther, J. Organometallic Chem., 1970, 22, 375. J. F. Brazier and D. Houalla, Bull. SOC.chim. France, 1970, 1079. J. Koketsu, S. Kojima, and Y. Ishii, Bull. Chem. SOC.Japan, 1970, 43, 3232. J. Barycki, P. Mastalerz, and M. Soroka, Tetrahedron Letters, 1970, 3147. J. S. Clovis and F. R. Sullivan, Tetrahedron Letters, 1971, 2263. A. K . Sheinkman, G. V. Samoilenko, and S. N. Baranov, J. Gen. Chem. (U.S.S.R.), 1970, 40,671.

N. Schindler and W. Ploger, Chem. Ber., 1971, 104, 2021.

72

Orgmophospharrrs Chemistry

KCII=CK’.CO.NH,

+ (EtD),P 40 ‘11

EtO- N a ’ 60-70

:c

/I (EtO),P*CHR.CHR’ I C 0 . N H,

I

c1- co hlt2

vary from pure cis-(26) to a mixture of cis- and truns-(27),depending on the ynamine, and were analysed on the basis of differing J p w ~values (1315 Hz for cis and 4 2 4 7 Hz for trans). A number of additions of secondary phosphites to Schiff bases have

Tervalent Phosphorus Acids

X

=

73

OorS

+

It

, P(OR),

I r\ 111

x

/c=c, NR',,

cis

(26)

been reported. In one of these l7 a kinetic study has shown the reaction to be first order in each reagent and acid catalysed. It is suggested that the configuration of the Schiff base is important in controlling its reactivity. Addition-elimination reactions of phosphites with chlorovinyl sulphonium salts (28) have been used to prepare phosphonomycin derivatives (29).18 Another new route to these antibiotics involves the addition of secondary phosphites to chloroacetaldehyde, followed by dehydrohalogenation to give the diethyl phosphonate (30).

0

I1

( Et0)2PH

+

CICH,-CI 10

30)

l9

N. S. Kozlov, V. D. Pak, and 1. N. Levashov, Doklady Akad. Nuuk Behruss. S . S . S . R . , 1970, 14, 243 (Clretn. Abs.. 1970, 73. 13 781h). R. A . Firestone. G . P., 2 004 879 (Cheni. A h . , 1971, 74, 76 5 2 5 y ) . T. Agawa, T. Kubo, and Y . Ohshiro, Syjithrsis, 1971, 27.

74

Orgunophosphoriis Clientistry

A kinetic study 2o of the previously reported 21 substitution of aromatic nitro groups by tervalent phosphorus has established an aromatic SN2 mechanism. Similarities in values of activation energies, and in relative reactivities of phosphite and phosphonite esters, between this displacement and the Arbusov reaction 22 suggest a related mechanism (31), while the lack of reactivity of p-dinitrobenzene is attributed to the need for ‘intramolecular’ solvation (32). The exclusive formation of ethyl nitrite, rather than other isomers, is confirmed from the decomposition of triethoxy(ethy1)phosphonium fluoroborate (33) in the presence of silver nitrite. A mechanism involving quinquevalent phosphorus 23 (34) still seems applicable, particularly in view of the recent mechanistic work on the Arbusov react ion .5

N 0,

‘:I>( 0 R ) 3

(32)

0 II (Et0)zPEt

OEt i .OEt

+

EtONO

OEt

I

-P-OEt II

+ RONO

0

N=O

(34) 2o

2a

J . 1. G. Cadogan and D. Eastlick, J . Chem. SOC.( B ) , 1970, 1314. J . I. G. Cadogan, D. J. Sears, and D. M. Smith, J . Chem. Sor. (C), 1969, 1314. G. Aksnes and D. Aksnes, Acra Chem. Scand., 1964, 18, 38. B. J. Walker in ‘Organophosphorus Chemistry,’ ed. S. Trippett, (Specialist Periodical Reports), The Chemical Society, 1971, Vol. 2, p. 78.

75

Tervalent Phosphorus Acids

The reaction of tetraphenylcyclopentadienone (tetracyclone) with dialkyl phosphites 24 has invoked further interest. Miller 25 has shown that reactions at 20 “C in the presence of sodium bicarbonate lead to products (35) and (36), with phosphorus substituted at carbon rather than oxygen. Quite different products (37) and (38) are obtained at 160 “C, although whether (38) is obtained from initial attack at oxygen or carbon is still unresolved.

l’tl&p,l I’tl’

Y

c‘ ”’l I’ll/-

)$!;

11 +

f ’(0hle ) 2 Ptl

1 ’

I’tl

(37)

The different products obtained from the analogous reaction of diphenylphosphine oxidez6 are explained in terms of the hardness of nucleophilic centres involved. Similar reactions with 2-methyl-3,4,5-triphenylcyclopentadienone gave the phosphonate (39). Gallagher and Jenkins have Ph Ph

@ie P(OMe)2

0

11 0

(39)

investigated reactions of tetracyclone with phosphites, phosphinites, and pho~phonites,~’ and in n o case does a reaction occur unless a base is present. Methyl phenylphosphonite and tetracyclone, in the presence of a tertiary amine at room temperature, form the adduct (40) which could not be purified but was readily acetylated at oxygen by acetic anhydride. The addition of a protic solvent to the adduct (40) gave (41) as one pure isomer, while direct reaction of tetracyclone and methyl phenylphos24

2s

27

B. J. Walker in ‘Organophosphorus Chemistry,’ ed. S. Trippett, (Specialist Periodical Reports), The Chemical Society, 1971, Vol. 2, pp. 8&82. J. A. Miller, Tetrahedron Letrers, 1970, 3427. J. A. Miller, Tetrahedron Letters, 1969, 4335. M. J . Gallagher and I. D. Jenkins, J . Chern. SOC.( C ) , 1971, 210.

76

0rganophosph or us Chemistry

phonite in refluxing benzene, without the isolation of (40), led to a mixture of isomers of (41). The reaction of dimethyl phosphite with tetracyclone in the presence of a base gave a complex mixture of products, including the salt (42). Gallagher and Jenkins suggest that their results are best explained by an enhanced electron density of the cyclopentadienone ring [i.e. a contribution from (43)] although one piece of evidence for this, the absence of products of nucleophilic attack at carbonyl carbon, is no longer viable with the isolation of (35) by Miller.25

Ph

Ph

Ph

Gi<$)i [Base H ]

Ph

+

Ph

Ph

0

0

(42)

-+

(43)

A detailed kinetic study of the reaction of trialkyl phosphites (44) with b e n d has been carried out (see Chapter 2 for the reactions of a-diketones with trialkyl phosphites). The reaction is first-order in both phosphite and benzil and the rate constant increases with the dielectric constant of the solvent. The authors propose initial attack of phosphite at carbonyl carbon (43, in opposition to the original suggestion by Ramirez,2sb who proposed initial attack at carbonyl oxygen.

2ya

Y . Ogata and M . Yamashita, J . Amer. Chem. Soc., 1970,92,4670. Bhatia, and C. P. Smith, Tetrahedron, 1967, 2067.

F. Ramirez, S. B.

77

Tervalerit Phosphorus Acids

Phosphite additions to the diene systems (46) 2 9 a and (47),2abto give the new heterocycles (48) and (49) respectively, have been reported.

(OR?),

(48)

A wide range of addition reactions of phenylphosphonous acid has been studied with a view to determining the structure of phosphorus during the reaction (PI" or P') and the site of initial attack.30 Attack at carbonyl carbon is deduced from the products [a-hydroxyphosphinic acids (SO)] of reactions with aldehydes and ketones (although no account is taken of possible attack at oxygen followed by rearrangement). ap-Unsaturated ketones undergo varying degrees of attack at carbonyl or Michael additions, depending on their substituents. Carbonyl carbon also appears to be the site of initial attack, and rate controlling, in the reaction of acetic anhydride with P1" n u ~ l e o p h i l e s . ~ ~ The structure of the adduct formed from triethyl phosphite and diphenyl keten, which has been the subject of some speculation, is now shown to be (51).32

81

32

K. Burger, J. Fehn, and E. Moll, Chem. Ber., 1971, 104, 1826. M. M. Sidky and M. F. Sayed, Terrahedron Letters, 1971, 23 13. I. G. M. Campbell and S. M. Raza, J . Chem. SOC.( C ) , 1971, 1836. J . Koketsu, S. Kojima, S. Shizuyoshi, and Y. Ishii, Kogyo Kagaku Zasshi, 1970, 73, 1004 (Chem. Abs., 1970, 73, 98 138f). J . E. Baldwin and J . C. Swallow, J . Org. Cheni., 1970, 35, 3583.

Organopkosphoriis Chemistry

78

The various reactions of aminophosphines with ketones have been disReaction of (52) with benzaldehyde presumably takes place by attack at carbonyl carbon followed by a proton shift.34a The same site of initial attack is suggested for the reaction of pyruvate esters with (53),34" although in this case it is followed by rearrangement. The reaction of P"' esters with acid chlorides has been reinvestigated,35 and used as the first step in a new synthesis of a-diazophosphonates (54).36

(RO),P-O-C-HK It I N COOK'

Ar

+ (McO),P

(54)

--

(RO),&O--C-R I I NHAr COOK'

II +(MeO),P.COR

N.NHTS

Horner 37 has applied the same reaction (55) to the continuing problem of converting carboxylic acids to aldehydes, the overall yield varying from 40-90% depending on R. 33

3w

R. Burgada and J. Roussel, Bull. SOC.chim. France, 1970, 192. A. N. Pudovik, E. S. Batyeva, and V. D. Nesterenko, J . Gen. Chenr. (U.S.S.R.), 1970, 40,468. A. N. Pudovik, I. V. Gur'yanova, and L. Kh. Rakhmatullina, J . Gen. Chem. ( U . S . S . R . ) , 1970, 40, 1471. Pudovik and T. M. Sudakova, Doklady Akad. Nauk S.S.S.R., 1970, 190, 1121 (Chem. Abs., 1970, 72, 132 87711). R. S. Marmov and D. Seyferth, J . Urg. Chern., 1971, 36, 128. L. Horner and H. Roder, Chem. Ber., 1970, 103, 2984.

m A. N. 38 37

Tervalent Phosphorus Acids

79

The Perkow reaction3Rhas been the subject of a number of reports. a-Halogenothioketones and trial kyl phosphites react to give (56) and (57), both of which result from initial attack at carbonyl carbon.3B Borowitz and his co-workers have used the Perkow reaction in the regiospecific alkylation of ketones.4o Vinyl phosphates (58), prepared from phosphites and a-halogenoketones, are split by organolithiums, or Grignard reagents, to give lithium, or magnesium, enolates (59) which undergo specific monoalkylation at carbon with alkyl halides. Me ( RO),I’

+ hlcCCH,CI I1

l

---+ (KO),I’--C--CH,CI I S-

S

-1

t

hl c I

c

‘!

( RO) ,i) - -(‘14,

t

l

( I
ci- s

I

.\rbuwv

0 hlc II I

(

S”

38

Ro)2P-c-cl~2 ‘/

II

( RO),PSC=CH,

I

hlC

I. J . Borowitz, H . Parnes, S. Firstenberg, and E. W. R. Casper, U.S. Gort. Reseurdr Development Report, 1970, 70, 66 (Chem. Abs., 1971, 74, 12 374r). E. Gaydou, G . Peiffer, and A. Guillemonat, Tetrahedron Letters, 1971, 239. I. J. Borowitz, E, W. R. Casper, and R. K. Crouch, Tetrahedron Letters, 1971, 105.

80

Organophosphorus Chemistry 0 /I

0

II

\ikJ

4

-

-+ M o-cH=CHR'

(RO)~P-O-CH=CHR'

+ ( RO)21'l<2

(59)

(58)

I

I<' CI I T 1 I 0 I I<

(iii) Attack on Nitrogen. Aziridinyl phosphonates (60) are formed by the reaction of phosphites with 2-iodoalkyl azides, and Hassner suggests that this takes place by initial attack on a ~ i d e . ~Diaziridinones l (61) undergo ring opening with triethyl phosphite to give, initially, isocyanates and the phosphite imide (62).42 However, under the reaction conditions these react further to give carbodi-imide and phosphate. 11 hlc 0

+

I C l I h l ~ * C I I h l e N ~ (RO),,P w

c.4 (0R

).

I I Mc (60)

Aminophosphines and amidoximes are reported to form the phosphoramide derivative (63); however, a similar reaction with amidoxime ethers gives the diazadiphosphetidine (64).43 0

II

c

N Me,

(Me,N),P

+ PhC-NH2 II

NOhIc

'' 42 43

2, *hleON=CPh*N, ,N*CPh=NOMe P NMe, (64)

A. Hassner and J. E. Galle, J . Amer. Chem. SOC.,1970, 92, 3733. F. D. Greene, W. R. Bergmark, and J . P ~ Z O JS ., Org. Chert?., 1970, 35, 2813. L. Lopez and J . Barraus, Cornpt. r e d . , 1970. 271, C, 472.

Tervaletit Phosphorirs Acids

81

The reaction of dialkyl and trialkyl phosphites with p-quinonedisulphonimides ( 6 5 ) has evoked considerable interest. Levy and Sprecher 4 4 isolated the nitrogen phosphorylated product (66) in 80% yield from a reaction with dialkyl phosphite, although other workers 46 claim that attack is at carbon to give (67). 0

II R SO,.N* I’ (OR I ).

0 g, N*SO,R

’

( R 0 ),P,40

II

+

0 R S O , * N H 11

Q””””

__j

N-SO,R ( 6 51

N H-SO,R

N t I *SO,I<

(67)

(66)

(iu) Attack on Oxygen. For many reactions where attack on oxygen is possible, certainly those involving a carbonyl group, opinion about the centre of attack often varies from report to report. Certainly, the nature of the products alone is not sufficient criterion (cf. Perkow reaction3n). Borowitz and his co-workers4s have carried out an extensive study of the reaction between trialkyl phosphites and fluorenone to give the oxyphosphorane (68). Attempts were made to trap the postulated intermediate (69) (similar intermediates have been isolated in other cases 47). Reactions

i

fluorenone

44

4t1

.i7

D. Levy and M. Sprecher, Tetrahedron Letters, 1971, 1909. M . M. Sidky and M. F. Zayed, Bull. Chem. SOC.Japan, 1970, 43, 1970, 3312. 1. J. Borowitz, M. Anschel, and P. D. Readio, J . Org. Chem., 1971, 36, 553. M . J . Gallagher and I. D. Jenkins, J . Chem. SOC.( C ) , 1969, 2605.

82

Organophosphorus Chemistry

at higher temperatures (150-180 " C ) give (70), which is also a decomposition product of (69) at these temperatures, and small yields of (71), which could be formed via a carbene.** Simple ketones, which cannot form a stable anion like (69), do not react and this is used as evidence for initial attack at oxygen. The anhydride (72) gives quite different products, (73) and (74), with tris(dimethy1amino)phosphine 4g to those previously obtained with triethyl p h ~ s p h i t e . ~The * formation of (73) and (74) is suggested to involve keten intermediates and an alternative mechanism is proposed for the phosphite react ion.

0

0

(73)

(74)

0

Isomeric products (75) and (76) are obtained from the reaction of perfluoroacetone with dialkyl p h o ~ p h i t e s . The ~ ~ relative proportions of the isomeric mixture depend on the alkyl group in the phosphite and the results are explained in terms of the polarity of the P-H bond and hence its direction of addition to the carbonyl group. Presumably, the balance in these cases is very finely adjusted, although these reactions are possibly more complicated than the results suggest. 4H

''

C. W. Bird and D. Y. Wong, Chem. Comm., 1969, 932. J. H. Markgraf, C. I. Heller, and N. L. Avery, J. Urg. Chem., 1970, 35, 1588. A. F. Janzen and R . Pollitt, Cnnari. J . C h m . , 1970, 48, 1987.

Terualent Phosphorus Acids

83 0

(RO),P
II + (CF,).?C‘O-+ (RO),I’OCH(CF3), (75)

+

0

II

(RO),PC(OH)(CF,),

(76)

The reaction of aldehydes with carbon tetrachloride in the presence of excess tris(dimethy1amino)phosphine has been used 61 to prepare vinyl It is suggested that the reaction takes dihalides in yields of 50-70%. place uia an intermediate salt (77), although the formation of this salt seems more likely to be analogous to the Perkow reaction than to involve attack on oxygen.

RCHO

+ CClp +

CCI3 I RCH-0+ (Mc,N),P + (Mc,N),P-OCHR + (Mc2N)J’CI3

I

CCI,

(77)

i

( h.lc,N

).j

P

RC H= C CI

Attack on Halogen. The well-known debromination of 1,2-dibrornides by tertiary phosphites has been investigated in terms of the structure of the dihalide.62 The mechanism of the reaction of tertiary phosphites with halogenoacetylenes has been investigated by two groups of 64 Initial attack of phosphite could be on carbon to give the anion (78), which can eliminate halide, or on halogen to give the ion pair (79) which leads to the same intermediate (80). In both cases an Arbusov reaction would give the isolated product (81). A much faster reaction for bromides than chlorides usually suggests attack on halogen, since bromine is more readily attacked by nucleophilic phosphorus. However, for phenyl acetylenes (82; R1 = Ph) these rates are about The presence of ethanol in the reaction mixture resolves this difficulty, since while the products from (82; X = CI) are virtually (0)

G1 *p

*.s

nc

J. C. Combret, J. Villikras, and G. Lavielle, Tetrahedron Letters, 1971, 1035. J. P. Schroeder, L. B. Tew, and V. M. Peters, J . Org. Chem., 1970, 35, 3181. A. Fujii, J. I. Dickstein, and S. 1. Miller, Tetrahedron Letters, 1970, 3435. P. Simpson and D. W. Burt, Tetrnhedron Letters, 1970, 4799.

84

Organophosphorus Chemistry

unchanged, those from (82; X = Br) contain an increasing amount of phenyl acetylene [presumably from the protonation of (79)] as the concentration of ethanol rises.K3These results suggest that both routes can operate in these reactions, depending on the halogen. Simpson and Burt have studied the same reactions in the presence of various amounts of ethanol and have plotted graphs of phosphonate (81 ; R1 = Ph) and phenyl acetylene produced against moles of alcohol added. Acetylene in the product reached a maximum (around 60%) when two moles of ethanol were added and stayed fairly constant beyond this, which suggests that the attack-on-halogen contribution to the mechanism is approximately 60%. The rest of the reaction presumably follows some other mechanism and the authors suggest the addition-elimination route (79) in view of the isolation of the phosphonate (83) from the reaction of tri(isopropy1) phosphite with the bromoacetylene (84).

(83)

B. Electrophilic Reactions.--Transesterification followed by rearrangement is a common route from simple phosphites to more complex phosphonates. This has now been applied 65 to the preparation of cyclic phosphonates (85). Both phosphites (86) and phosphoranes (87) containing phosphorus-hydrogen bonds are obtained from the cyclic biphosphite (88) and b ~ t a n o l . ~ ~ The preparation of the bicyclic phosphite (89) from tri(hydroxymethy1)phosphine and trimethyl phosphite has been reinvestigated 5 7 following reports that it could not be repeated. The reasons for the difficulties s6

s6 67

B. E. Ivanov, L. A. Kudryavtseva, and T. G. Bykova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 2063 (Chem. Abs., 1971, 74, 31 811x). H. Germa, M. Willson, and R. Burgada, Compt. rend., 1970, 270, C , 1474. J. Rathke, J. W. Guyer, and J. G. Verkade, J . Org. Chem., 1970, 35, 2310.

Tervalent Phosphor us A rids

85

+ BuOH

-+

-0Bu

+

appear to stem from the method of preparation of tri(hydroxymethy1)phosphine, by treatment of tetra(hydroxymethy1)phosphonium chloride with sodium hydroxide. This leads to various impurities, mainly water and acid, in the phosphine; however, an excess of base must also be avoided since the phosphine itself decomposes under these conditions. Some confusion still exists since a cautionary note appears in the text warning that the tri(hydroxymethy1)phosphine must be strongly basic (sic) for use in the transesterification reactions. The modified preparation of (89) is now claimed to be repeatable, although the yields are low (20-30%).

The alcoholysis and transamination of various aminophosphines have been studied as functions of the basicity of the attacking nucleophile and the substituents on p h o s p h o r u ~ . ~ As ~ might be expected the reaction is facilitated by electron-withdrawing groups on phosphorus. The hydrolysis of tris(dimethy1amino)phosphine (90) to phosphorous acid has been investigated using thin-layer chromatography and the amides (91) and (92) have been identified as intermediates. 68

6a

L. Fafaille and F. Mathis, Compf. rend., 1970, 270, C, 1138. J . P. Meille and A. Lamotte, Compr. rend., 1971, 272, C, 198.

4

86

The reaction parameters of the alcoholysis of NN’-bis(dipheny1phosphino)-SS-dimethylsulphodi-imine(93), to give SS-dimethylsulphodi-imine (94), have been determined by a kinetic study using n.m.r.60

(93)

(93)

C. Rearrangements.-The thermal rearrangement of di-t-butyl-2-propynyl phosphite (95) has been used in a new synthesis of phosphonomycin (96).’j1 The half salt (97) was obtained optically pure after a single crystallization.

I

Me

0 II ,011 1’.

D. Cyclic Esters of Phosphorous Acid.-There has been some controversy about the stable stereochemistry at phosphorus in cyclic phosphites and phosphonites; this now appears to be resolved by agreement in a series of papers. The stereochemistry of 2-alkoxy-4-methyl-l,3,2-dioxaphosphorins 6o

F. Knoll, K. W. Eichenhofer, K. D. Ziehn, and R. Appel, Chem. Ber., 1970, 103, 3623. E. J. Glamkowski, G . Gal, R. Purick, A. J. Davidson, and M. Sletzinger,J . Org. Chem., 1970, 3510.

Toriwletil Phorpfiorirs Acids

87

(98) has been studied by 1i.m.r. and dipole moment measurements.62 A variety of esters were prepared from the corresponding alcohol and phosphorochloridite and in each case the less stable isomer was obtained, since it could be isomerized (except when R = But) to the more stable one by traces of hydrogen chloride gas. The formation of the thermodynamically less stable isomer by this method of preparation appears to be fairly 66 The more stable isomer was truns-(99), with the alkoxy-group on phosphorus axial, while the less stable cis-compound appeared to be flipping rapidly between the two chairs (100) and (101) at room temperature. Verkade and co-workers come to similar conclusions63from an n.m.r. study of the cyclic esters (102) and (103), the stable configuration at phos-

( 102)

phorus of lone-pair equatorial, alkoxy-group axial, being virtually irrespective of the stereochemistry of other substituents. The temperaturedependent broadening observed in the n.m.r. of (102; R = C1 or Br) is due to intermolecular halogen exchange. Other workers 64 have used the fused ring system (104) and 4,Sdimethyl substitutions (105) to simplify n.m.r. studies by restriction to one chair form. In each case the stable configuration had an axial alkoxy-group at phosphorus. e2 e3

R4

C. L. Bodkin and P. Simpson, J . Chem. Soc. ( B ) , 1971, 1136. D. W. White, R. D. Bertrand, G. K. McEwen, and J. G. Verkade, J . Amer. Chem. SOC.,1970, 92, 7125. M. Haemers, R. Ottinger, J. Reisse, and D. Zimmerman, Tetrahedron Letters, 1971, 461.

Organophosphorits Chemistry

88

Bentrude and co-workers have published a number of papers65-67in which they use a 5-t-butyl group, originally, presumably, as a conformationlocking device. Isomeric mixtures of 5-t-butyl-2-methoxy-1,3,2-dioxaphosphorinanes (106), with a 9 : 1 predominance of the less stable isomer, were prepared from the corresponding phosphorochloridite.s6 Equilibration with acid gave > 90% of the more stable isomer. The stereochemistry of each isomer was determined by stereospecific oxidation to the corresponding phosphate and by an Arbusov reaction to give a phosphonate (however, see ref. 5). X-Ray analysis was used to determine the stereochemistry of these final products, confirming the more stable isomer as cis and the less stable as trans. N.m.r. suggests the conformation (107), with an axial al koxy-group, for the cis-isomer, while the trans-isomer appears to be largely (IOS), with both alkoxy and t-butyl axial (sic). The extreme preference for the axial-alkoxy configuration at phosphorus is explained in terms of anonieric effects and phosphorus oxygen bond parameters. OR

0R

OMe I

’

(108)

In an attempt to isolate the anomeric effects, analogous phosphonites have been studied.66? Equilibration of cis- (109) and trans-2-methyl5-t-butyl-l,3,2-dioxaphosphorinanes (1 10)demonstrated the thermodynamic preference for cis over trans (72% and 28% respectively at 40 oC).60This surprising result must mean that axial P-methyl is more stable than equatorial even when no anomeric effects are present, and the authors interpret their n.m.r. results in terms of two equilibrating conformers for trans-(1 10) us

6i

W. G . Bentrude and J . H. Hargis, J . Amer. Chem. Sot.., 1970, 92. 7136. W. G . Bentrude, K . C. Yee, R. D. Bentrand, and D. M . Grant, J. Airier. Chem. SOL.., 1971, 93, 797. W. G . Bentrude and K . C. Yee, Tetrahedron Lerrers, 1970, 3909.

Tervalerit Phosphorus Acids

89

and a single conformer for cis-( 109). Throughout this investigation the configurations were determined by assuming that oxidation to the phosphonate by nitric oxide at 0 “C involves retention of configuration.ss A

1

( 109)

( 1 10)

Similar results were obtained 6 7 from a study of 2-phenyl-5-t-butyl1,3,2-dioxaphosphorinane( 1 1 1) in that the cis-isomer was thermodynamically more stable than the trans. However, in this case even the transisomer adopts a conformation (1 12) with the P-phenyl group and, perforce, the t-butyl group axial. A similar situation has already been noteds5 in the phosphite (108), and it may be that the special case of a phenyl group produces some type of pseudo anomeric effect.

(Ill)

Russian workers 69 have studied secondary cyclic phosphites ( I 13) and (114). Unfortunately, the situation is far from clear since cis-(115) isomerizes to tmns-(l16) on tand ding,"^ but (1 17) is suggested to be thermodynamically more stable than (1 1 8).‘jgb This apparent contradiction could be explained by either an incorrect assignment of isomers or a 1,3-interaction of the 4-methyl group in (114).

fl

0

( 1 15)

””

( 1 16)

J . Michalski, A . Obruszek. and W. Stec, Cheni.Contrn.. 1970, 1495. E. E. Nifant’ev, A. A . Borisenko, I. S. Nasonovskii, and E. I. Matrosov, Doklady Akad. Nauk S . S . S . R . , 1971, 196, 121 (Client. Ahs., 1971, 74,99 353e). E. E. Nifant’cv, 1. S. Nasonovskii, and A . A. Borisenko, J . Gen. Chent. (U.S.S.R.),1970, 40, 1239.

90

Or~ariaphospharusChemistry

( 1 17) I1 I % ) Cyclic phosphorochloridites are reported to undergo rapid inversion at p h o s p h o r ~ s .This ~ ~ has now been shown to depend on the purity of the sample, and pure samples, which show high barriers to inversion, have been obtained,

E. Miscellaneous Reactions.-Des u I ph uriza t ion of 35Sla be1led benzy 1 trisulphide (1 19) with triphenylphosphine leads to predominant removal of the central sulphur atom, while reaction with tris(diethylamin0)(PhCH,S)? + P ~ I , P = ~ ” S PI1CH, S -33S- Sc‘ H,Ph

I’’Y

(1 19)

T)3p (PhCH,), 35SS+

( EtIN),P=S

phosphine removes a terniinal atom almost e x c l ~ s i v e l y . The ~ ~ formation of tris(trialkylsily1)thiophosphate ( 1 20), from the reactions of the secondary phosphite (121) with sulphur,73is thought to take place via disproportionation of the intermediate (1 22). (Me,SiO),P,

H0

t!

+S

,

135

---+

c-

( Me S i 0),P

(Me,SiO),P=S

4s ‘OH

(122)

A useful new method of preparing arylphosphonates ( I 23) involves the reaction of trialkyl phosphites with aryl halides in the presence of a nickel catalyst.74 The suggested mechanism is via the nickel complex (124), and is non-radical. 0

II + ArX -Ne ArP(OEt), Nix

(EtO),P

ic

(60-9U;J

(123)

X2Ni[P(OR),l, ( 70

’l

n is 74

123)

B. Fontal and H. Goldwhite, Tetrahedron, 1966, 22, 3275. R. H. Cox, M. G. Newton, and B. S. Campbell, J . Amer. Chem. Soc., 1971, 93, 528. D. N. Harpp and D. K. Ash, Chem. Comm., 1970, 81 1. N. F. Orlov, M. S. Sorokin, and E. F. Shestakov,J. Ge~r.Chem. ( U . S . S . R . ) ,1970,40,687. P. TdVS, Chem. Ber., 1970, 103, 2428.

7croulerrt Phosphorits Acids

91

Japanese workers 7 5 have prepared diethyl phosphite in 43';; yield from the reaction of white phosphorus with ethanol and oxygen. Various phosphorylated derivatives of carbohydrates [e.g. ( I 25) and (126)] have been prepared by the reaction of suitable derivatives with dialkyl phosphi t e ~ . ~ ~ CH,OR

CH,OAc

Mi (125)

3 Phosphonous Acid and its Derivatives Two preparations of diesters of phosphonous acid have been r e p ~ r t e d78. ~ ~ ~ One of these,77which claims to be the first preparation of these derivatives, involves the reaction of ammonium hypophosphite with trialkylsilylamines to give bis(trialkylsily1) esters (127) in excellent yield. These compounds are extremely reactive, e.g. they are spontaneously inflammable in air. Dialkyl phosphonites (128) have also been prepared 78 by the reduction of

+ 2R3SiNH2

NH4H2P02

a

(R,SiO),PH (127) the corresponding chloride with organotin hydrides. (RO),PCI

+ R,SnH,_.,

-

+ NH, + 2RNH2

(RO),PH (128) Phenylphosphinic anhydride (1 29) decomposes on heating to give phenylphosphine, phenylphosphonic acid ( 1 30), and pentaphenylcyclopentaphosphine. Phenylphosphinidene (PhP:) has been shown to be an ~ ~trapping with benzil to give the intermediate in this d e c o m p o ~ i t i o n ,by adduct (131) in very low yield. The phenylphosphine is suggested to be formed by a complex ionic reaction between pentaphenylcyclopentaphos-

0

II

phine and phenylphosphonic acid. Phosphorous [HP(OH),] and phos0

II

phonous (H,POH) acids also react with the cyclic phosphine to give phenylphosphine and other products. 76 76

77

7n

@ :

Y . Okamoto and H . Sakurai, Yukagnku, 1970, 19,968 (Chetn. A h . , 1971,74, 12 529v). H. Paulsen, J . Thiem, and M . Moner, Tetrahedrori Letters, 1971, 2105; H . Paulsen, W. Greve, and H. Kulme, ibid., p. 2109. M . G. Voronkov and L. Z . Marmur, J . Gen. Chem. (U.S.S.R.), 1970, 40, 2121. 1. F. Lutsenko, M. V. Proskurnina, and A . A. Borisenko, Organometallic Chem. Synthesis, 1971, 1, 169. M. J. Gallagher and I. D. Jenkins, J . Chetn. SOC.( C ) , 1971, 593.

92

Organophosphorus Chemistry

The kinetics of the oxidation of phenylphosphonous acid (132) to phenylphosphonic acid by chromic oxide have been investigated.R0 The reaction, which is first order in Crv', is catalysed by both acid and pyridine and the mechanism suggested involves the initial formation of a complex between chromic acid and the tervalent form of the starting acid. Ratedetermining decomposition of this complex is followed by rapid oxidation by CrV. In accord with the current interest in stereochemistry at phosphorus a number of optical studies on phosphonous derivatives have been carried out. Benschop and his group 81 have achieved a partial resolution of alkyl alkylphosphinates (1 33) by stereospecific inclusion in cycloarnyloses. Optical purities in the range 20-80"/, were obtained. 0

II RPOR I4

(133)

Isopropyl (R)-(- )-methylphosphinate (1 34) has been prepared n2 in > 90% optical purity by Raney nickel desulphurization of optically pure 0-isopropyl ( S ) - (+ )-methylphosphonothioate (1 35). The phosphonate (134) is rapidly racemized by base, but not by acid, unlike secondary phosphine oxides 83 [although whether these have been prepared optically active now seems doubtful 84 (see Chapter 4)]. The phosphinate (134)can be reconverted into 89% optically pure (S)-( )-(135) by addition of sulphur in dioxan. As shown in the Scheme, a series of interconversions has been used to establish the configurations.

+

R2

83 84

K. K. Sen Gupta, Bull. Chem. SOC.Jclpan, 1970, 43, 590. H. P. Benschop and G. R. Van den Berg, Chem. Comm., 1970, 1431. L. P. Reiff and H. S. Aaron, J . Amer. Chem. SOC.,1970, 92, 5275. 0. Cervinka, 0. BElovskjr, and M . Hepnerva, Chem. Comm., 1970, 562. W. B. Farnham, R. A. Lewis, R. K . Murray, and K . Mislow, J . Amer. Chenr. Soc.. 1970, 92, 5808.

Tcrvalent Phosphorus Acids

93

Optically active O-isopropyl (S)-( - )-methylphosphinothioate(1 36) has been prepared for the first time 85 by reaction of isopropyl(R)-( -)-methylphosphinate ( 1 37) with P,S,,. The retention of configuration at phosphorus during this conversion was established by the formation of the two enantiomers, ( 1 38) and (1 39), of O-isopropyl S-phenyl methylphosphonodithioate by separate routes of known stereochemistry. 0

OH

0

'

y/largely ( 34)

( 1 35)

/retention 1

7

0

PriO

COCI,

CI I

Rs L.

J. Szafraniec, L. P. Reiff, and H. S. Aaron, J .

639 1.

Amer. Chern. So t... 1970, 92,

Benschop and his co-workers A R have shown that ethyl phenylphosphinate (140) may be converted into ethyl alkylphenylphosphonites (141) by a variety of routes based on the Arbusov reaction, with retention of configuration in each case.

G . R. Van den Berg, D. H . J . M. Platenburg, and H . P. Benschop, C'hetn. Cu/rr~n., 1971. 606.

6 Q uinq uevalent

Phosphorus Acids BY N. K. HAMER

1 Phosphoric Acid and its Derivatives A. Synthetic Methods.-There have been no strikingly new approaches to the general problem of phosphorylation, but several ingenious methods of preparing suitable active esters under mild conditions have been reported. Typical of these is the reactive intermediate (1) formed from reaction of a mono- or di-ester of phosphoric acid with (2), itself produced by reaction of triphenylphosphine with bis(2-pyridyl) disulphide (preferably in the presence of mercuric ion as scavenger for the 2-mercaptopyridine liberated).

Ph,P

+

osL

(

ROPO,H,

--+

A

0 11 Ph,POP-OR +

I

OH

OH (3)

Compound (1) phosphorylates phosphate monoesters and alcohols, although with the latter a considerable excess of alcohol is necessary to obtain satisfactory yie1ds.l In the absence of mercuric ions the milder phosphorylating species (3) can be isolated which converts monoalkyl phosphates to pyrophosphate diesters in good yield but does not react appreciably with alcohols unless catalytic amounts of boron trifluoride are added. Amine salts of (3) are converted to phosphoramidates on heating. In the presence of silver ions, 0-esters of thiophosphoric acid behave as phosphorylating agents and a very mild and convenient procedure suitable for preparing labile unsymmetrical pyrophosphate diesters, such as the 'L

T. Mukaiyama and M. Hashimoto, Bull. Chem. Soc. Japan, 1971, 44, 196. T. Mukaiyama and M. Hashimoto, Tetrahedron Letfers, 1971, 2425.

96

Organophosphorus Chemistry

nucleotide coenzymes, involves reaction of the disilver salt of a monoalkyl phosphate with an 0-alkyl phosphorothioate:3

R'OPO.,SH,

0

0

I OH

I OH

II II + Ag,03POR2 + R'O-P-O-P-OR2

ortho-Phenylene phosphorochloridate (4) has been proposed as a powerful and versatile reagent for the preparation of monoalkyl phosphates since the cyclic triesters ( 5 ) are easily hydrolysed with ring opening to give the diesters (6), from which the o-hydroxyphenyl group is readily removed

(4)

by a variety of oxidizing agents (bromine in buffer, periodic acid, or lead tetra-acetate) or by hydrogenolysis.6 Since the intermediate triesters phosphorylate alcohols readily and are accessible from (6) and DCC they have been used as a general route to mixed diesters of phosphoric acid.6 The preparation of phosphate esters has been reviewed and full details have appeared of the use of 2-chloromethyl-4-ni trophenyl esters (reported last year) in the synthesis of monoesters and mixed dialkyl esters of phosphoric acid. S-Alkyl monoesters of thiophosphoric acid have not hitherto been readily accessible compounds owing to indifferent yields and lengthy and difficult isolation procedures. A simple preparative route involves reaction of 00-di-t-butyl hydrogen phosphorothioate with the appropriate alkyl halides followed by elimination of the t-butyl groups with dry hydrogen chloride in dichloromethane :* 0 0 It I 4 IiCI 4 (ButO),POSH --+ (ButO),P ---+(HO),P / \ SK SR Perkov reaction of a trialkyl phosphite with a-chlorothioacetone leads to the S-phosphorylated enol derivative (7).9 Not unexpectedly, the phosphonate ester (8) is formed as a by-product, and in view of studies on the Perkov T. Hata and I. Nakagawa, J . Anter. Chem. Suc., 1970, 92, 5516. T. A. Khwaja, C. B. Reese, and J . C. M . Stewart, J . Chem. Sor. ( C ) , 1970, 2092. J . Calderon and C. Cruz, Te/rahedrurr Le//ers, 1971, 1069. C . Chiglione, Bill/. SOC.Phurm. Mnrseilles, 1969, 18, 1 1 7 (Chenr. Abs., 1970,73, 108 887). Y . Mushika, T. Hata, and T. Mukaiyama, Bull. Chem. Suc. Japnrt, 1971, 44, 232. A . Zwierak and R. Gramze, Z . Nutiirfursch., 1971, 26b, 386. E. Gaydon, G . Peiffer, and A. Guillemonat, TerruheclronLetters, 1971, 239.

Quinquevalent Phosphorus Acids

97

reaction it seems probable that the relative amounts of (7) and (8) would depend on the detailed structure of the thioketone. This, coupled with the relative inaccessibility of the latter, necessarily limits the general utility of the method. The readily available 00-dialkyl phosphorodithioates provide convenient routes to triesters of phosphorotetrathioic acid (9) l o (by treatment with phosphorus pentasulphide) or dialkyl phosphorochloridothioates l1 (by oxidation with chlorine). S

(RO),,P

II + ClCH2CMc --+

0

MC

\

II

C - S -I'(OR)z

//

S

0

II II + McC--CJ-T,--P(OR)~

S

Phosphorylation of cholesterol followed by the normal hydrolytic work-up gives the phosphate monoester,12 not the symmetrical pyrophosphate diester as previously claimed. Cholesteryl phosphorodichloridate and some related steroidal phosphorodichloridates have been prepared from the action of pyrophosphoryl chloride on the appropriate alcohol :12

Several of these steroid derivatives underwent elimination of phosphorodichloridate anion, giving hydrocarbon products, rather than ester formation when treated with methanolic pyridine. Pyrophosphoric acid itself has been used to phosphorylate (2-hydro~ymethy1)pyridine.l~ General preparative procedures for the preparation of N-alkyl phosphoramidic dichlorides (10) and NN'-dialkyl phosphorodiamidic chlorides (1 I ) l4 from the appropriate amine and phosphoryl chloride have been described. With weakly basic amines, pyrophosphoryl chloride was V. S. Blagoveshchenskii and S. N. Vlasova, Zhur. obshchei Khim., 1971, 41, 1032. H. Roszinski and H. Harnish, G. P. 1 801 432 (Chem. Abs., 1970, 73, 34 790). u R. J. W. Cremlyn and N. A. Olsson, J . Chem. SOC.(C), 1970, 1889; ibid., 1971, 2023. l 3 Y. Murakami, H. Sadamori, H. Kondo, and M. Tagaki, Bull. Chem. SOC. Japan, 1970,

*O

l1

l4

43, 25 18. R . J. W. Cremlyn, B. B. Dewhurst, and D. H . Wakeford, J . Chem. Soc. ( C ) , 1971, 300.

98

Organophosphorirs Chemistry

necessary to obtain good yields of (10). Symmetrical pyrophosphoramides (12) were formed from (1 1) on treatment with silver oxide, and other routes to symmetrical and unsymmetrical pyrophosphoramides were also in~estigated.'~

(10)

(12)

( 1 1)

Interest in possible prebiotic phosphorylating agents continues, and a study of the phosphorylation of glucose by cyanogen and orthophosphate in H2180has shown that the formation of the a- and 18- anomers of glucose1-phosphate probably results from activation of the inorganic phosphate.16 The imidoyl phosphate (1 3) was suggested as the active species. In the reaction of glycine with cyclic trimetaphosphate in aqueous solution, which leads to peptide bond formation, it appears that initial phosphorylation of the amino-group occurs, leading to (14). This undergoes intramolecular nucleophilic attack by the carboxy-group to give the cyclic mixed anhydride (1 5 ) , which is proposed l7 as the key acylating species. I I2C),PO, , C-CN

4

14 N (13)

0,

,o-

O/p'O I I 0=P, ,P=O

/ o \ 0-

0-

0

NH,

+ c\/H,

COOtI

7 -+ CH2 \

0

0

II II N H - P- 0-P -0- 1'- 0 I I II

/bL^ A-

(II

c-0II

0

H,C-N

I

0J-O

(14)

I -r

\J

J 0

A O-

Phosphorylation of enolate ions by dialkyl or diary1 phosphorochloridates gives exclusive 0-phosphorylation and it appears that the product geometry in acyclic systems is determined by the polarity of the solvent and R. J. W. Cremlyn, B. B. Dewhurst, and D . H. Wakeford, J . Chern. SOC.(C), 1971,2028. C. Degeni and M. Hallmann, J . Chem. SOC.( C ) , 1971, 1459. N. M. Chung, R. Lohrmann, L. E. Orgel, and J. Rabinowitz, Tetrahedron, 1971, 27, 1205.

Qiririyireccilctrt Pliosplror-us Acids

99

the size of the cation.ln Large cations and non-polar solvents result in predominant formation of the cis-isomers ( I 6) whereas the more stable trans-isomers (1 7) are formed in polar solvents - an effect which is attributed to extensive ion association in the non-polar solvents.

(17)

(16)

The reaction of frans-l,2-dichloroethylenewith phosphorus trichloride in the presence of oxygen has been shown to give the phosphorodichloridate (1 8),lQ not the phosphonodichloridate ( I 9) suggested previously. This reaction is almost certainly free-radical in character and possible chain mechanisms were proposed.

c1

+ c1

0, + rc1,--+

CHCI,CH,

,C'

0 // 0-PCI,

(18)

4

CH CI .C HCI-PCI (19)

N-Chloro- and NN-dichloro-phosphoramidate esters (20) and (21) are readily prepared from the parent phosphoramidate by direct chlorination in mildly acidic solution20 but when R = Ph, the use of t-butyl hypochlorite is preferable,,l to avoid chlorination of the aromatic nucleus. These compounds behave as pseudohalogens, (21) reacting with olefinic compounds such as styrene to give (22), which is also formed by chlorination of the N-phosphorylaziridine (23).21

I

c1

(RO),P=O

(21)

(20)

rth

//0

A

(22)

N-P (OR),

(23) l8

2o 21

B. Miller, H. Margulies,T. Drabb, and R. Wayne, Tetrahedron Letters, 1970, 3801,3805. C. B. C. Boyce and S. B. Webb, J. Chem. SOC.( C ) , 1971, 1612. A. Zwierak and A. Koziara, Tetrahedron, 1970, 26, 3521. L. N. Markovskii, A. M. Pinchuk, and T. V. Kovalevskaya, Zhur. obshchei. Khim., 1970,40, 543, 101 1.

Organophosphorus Chemisrry

100

B. Solvolysis of Phosphoric Acid Derivatives.-Interest continues in neighbouring-group participation in the solvolysis of phosphate esters. As a potential model compound for investigating the mechanism of ri bonuclease action, the phenyl hydrogen phosphate ester of cis-3,4-tetrahydrofurandiol (24) has been the subject of a detailed study.22 Above (and probably also below) pH 4 hydrolysis gives solely the cyclic phosphate (25)

I

Of 1

resulting from intramolecular nucleophilic displacement of phenoxide by the cis vicinal hydroxy-group. In contrast to an earlier tentative suggestion, there is no evidence for a pentacovalent intermediate and the reaction appears, in the pH range studied, to be a straightforward ,S"2 process in which the dianion, the monoanion, and the neutral species participate. Participation of the neighbouring hydroxy-group has also been invoked 23 to account for the increased rate of hydrolysis of the dianion, the monoanion, and the neutral zwitterion (26) compared with 2-pyridylmethyl dihydrogen phosphate itself, but here it appears that intramolecular general-acid rather than nucleophilic catalysis is involved. Intramolecular general-acid catalysis by the carboxy-group accounts also for the hydrolytic lability of the monoanion (27) of o-carboxyphenyl dihydrogen phosphate.24

(26)

(27)

The full paper has appeared on the solvolysis of the dibenzyl ester (28) of phosphoenolpyruvic acid and on the related phosphonate ester (29).26 Reversible phosphoryl migration from the enol oxygen to the carboxygroup occurs readily in (28) and (29) but only to a small extent - and probably not reversibly - in the monoanion (30) and phosphoenolpyruvic acid itself. These observations are readily accounted for in terms of the expected ease of pseudorotation between the various configurations of the 22

UL

D. A. Usher, D. I. Richardson, and D. G . Oakenfull, J . Amer. Chem. Sor., 1970, 92, 4699. Y. Murakami, J . Sunamoto, and H . Ishizu, Chem. Comm., 1970, 1665. Y. Murakami, Nippon Kagaku Zasshi, 1970, 91, 185 (Chem. Abs., 1970, 73, 24 452). K . J. Schray and S. J. Benkovic, J . Amer. Chem. Sor., 1971, 93, 2522.

Quinquevalent Phosphorus Acids

101

pentacovalent intermediates (3 1). Similar observations have been made in a study of the solvolysis of dialkyl phosphate esters (32) of salicylic acid.2R

-

0

HK, ,c-0-P, HO,C (28) X (29) X (30) X

=

= =

II ,OCH,Ph

x OCH,Ph Ph 0-

(35)

The anion of (32) hydrolyses faster than (32) itself but both proceed lo7 times faster than corresponding esters lacking the o-carboxygroup. In the case of the anion it was shown that nucleophilic attack by the o-carboxylate anion occurred, leading [via an intermediate (33)] to the acyl dialkyl phosphate (34), which underwent rapid hydrolysis to salicylic acid and dialkyl phosphate. Although not directly demonstrable, it is probable that a similar intramolecular nucleophilic mechanism operates for hydrolysis of the free acid. In this case the product is the aryl alkyl hydrogen phosphate (39, and it was suggested that the differing products might be accommodated on the basis that phosphoryl migration was reversible whereas the exocyclic loss of ROH from (33) was not. Methyl OS-ethylene phosphorothioate (36) undergoes solvolysis in aqueous base with P-S cleavage whereas US-ethylene phosphorothioate and the phosphonothioate (37) give exclusive endocyclic P- 0 cleavage.27 To explain this it was assumed that initial attack of hydroxide gives the intermediate (38a), in which the more electronegative alkoxy-group is apical, but that when R = OMe pseudorotation to (38b), bringing the better leaving-group to an apical position, is much more favourable than 21 R. H. Bromilow, S. A. Khan, and A. J. Kirby, J . Chem. Soc. ( B ) , 1971, 1091. 27

D. C . Gay and N. K . Hamer, Chetn. Cotnm., 1970, 1564.

when R = 0- or Ph. Such an explanation implies that displacements involving expulsion of thiols from mixed OS-esters of phosphorus acids should not proceed with the inversion expected of a simple SN2(P) reaction, and stereochemical evidence is appearing (see later) to suggest that this is so.

I

(36) R

7

OMC

(37) R

-

Ph

OH (3Xa)

The mono- and di-anions of the mixed anhydride (39) are labile in aqueous solution and, on the basis of the solvent isotope effect and the small value of AS*, it was concluded that unimolecular elimination of sulphur trioxide was occurring.'* However, the selectivity factor for sulphonation of methanol and water in a mixed solvent system was smaller than that exhibited by gaseous sulphur trioxide. Cyanovinyl dihydrogen phosphate (40) (from orthophosphate and cyanoacetylene in aqueous solution) hydrolyses at a rate independent of p H in the range 7-11 and Here again a the rate increases by a factor of only 4 in the range 7-1.3. unimolecular breakdown with elimination of monomeric metaphosphate ion was but since the breakdown of (40) was catalysed by orthophosphate ions, some degree of nucleophilic participation is likely. Nevertheless, it was concluded that (40) was probably not an important prebiotic phosphorylating agent.

From studies of a series of N-arylcarbamoyl dihydrogen phosphates (41)30it was concluded that solvolysis of both the mono- and di-anions proceeds with P-0 cleavage. The small value of p for the monoanions suggests a cyclic hydrogen-bonded transition state but otherwise the general behaviour is similar to that of other acyl dihydrogen phosphates. Cupric ion strongly catalyses (by about lo4 times, at pH 4) the hydrolysis of the aryl dihydrogen phosphate (42) bearing an o-imidazolyl group 31 and as so s1

S. J. Benkovic and R. C . Hevey, J . Amer. Chem. SOC.,1970, 92, 4971. J. P. Ferris, G. Goldstein, and D. J. Beaulieu, J . Amer. Chern. SOC.,1970, 92, 6598. C . M . Allen and J. Jamieson, J . Amer. Chem. SOC.,1971, 93, 1434. S. J . Benkovic and L. K. Dunikowski, J . Amer. Chem. Soc., 1971, 93, 1536.

Quinquei~alet~t Phosphorus Acids

I03

the variation in rate with cupric ion concentration indicates rapid preequilibrium formation of a 1 : 1 complex. The rate enhancement is probably due to the copper acting as a Lewis acid in the complex.

Ar N HCO-OPO,l-l,

(41) (32)

Micelles of cetyltrimethylammonium bromide catalyse the reaction of hydroxide ion with bis(2,4-dinitrophenyl) hydrogen phosphate anion,32 presumably by offering electrostatic assistance to the approach of two negative ions. In support of this view, large anions with bulky organic groups inhibited the catalysis by competing for micelles and the reaction was also inhibited by micelles of an uncharged detergent, possibly due to competitive adsorption of the substrate. The expulson of p-nitrophenate from diphenyl p-nitrophenyl phosphate by hydroxide ion was catalysed by micelles of the cationic detergent (43).33 Since (43) did not catalyse the

reaction of fluoride ion with the substrate, it was concluded that it was probably operating as a nucleophile rather than a general-acid catalyst. Micelle formation can, in itself, influence the rates of hydrolysis of monoalkyl phosphates bearing bulky alkyl groups since, at concentrations < 0.02 mol I - l , the first-order rate constant for the hydrolysis of methylprednisolone-2 1 phosphate is independent of concentration and has a pH-rate profile qualitatively similar to that of monomethyl phosphate; at higher concentrations the rate shows an increase and the pH-rate profile changes.34 The phosphorimide (44) hydrolyses in aqueous solution to the phosphoramidate (45) and the rate dependence is well represented on the basis of a reversible protonation (pK, 6.4) followed by rate-determining formation of However, studies in H2180 indicate that the molar incorporation of l80in the product varies from 0.22 at pH 4 to 0.81 at

-

32

39 34

aa

G. J. Buist, C. A. Bunton, L. Robinson, L. Sepulveda, and M. Stam, J . Amer. Chem. SOC.,1970, 92, 4072. C. A. Bunton, L. Robinson, and M. Stam, J . Amer. Chem. SOC.,1970, 92, 7393. G. L. Flynn and D. J. Lamb, J . Pharm. Sci.,1970, 59, 1433. R. K. Chaturvedi, T. C. Pletcher, C. Ziondrou, and G. L. Schmir, Tetrahedron Lerrers, 1970,4339.

104

Organophosphorus Chemistry

pH 7, indicating that the protonated (44) must decompose by at least two mechanisms. In the absence of further data this could be accommodated on the basis of a pH dependence for the relative rates of attack by water on carbon or phosphorus. (EtO),P=NPh

I"

0 t It.j.3 // (EtO),PNHPIi ---+ (EtO),P \

(44)

N H I'h

(45) An acid-catalysed hydrolysis is observed for diary1 hydrogen phosphates except in those cases where an alkoxy-group is ortho or para to the phosphate. The rate maximum, in perchloric acid 36 of concentration 4 moll-', shown by these latter compounds is a consequence of the combined effects of ionic strength and activity of water on the rates. The rate of hydrolysis of ally1 dihydrogen phosphate in strong acid shows Ho dependence, indicating unimolecular C-0 cleavage, which is also probably involved in the solvolysis of the neutral species.37 This latter is sufficiently fast to mask that rate maximum at pH 4.0, characteristic of monoalkyl phosphates, which is due to P-0 cleavage. The acid-catalysed hydrolysis of isopentenyl dihydrogen phosphate (46)(unlike hydrolysis of the monoanion, which is normal) appears to involve acid-catalysed hydration of the double bond followed by rate-determining elimination to form dimethylallyl dihydrogen phosphate, which undergoes a fast C-0 cleavage under the conditions.38 Although the cyclic ester (47) was considered as a possible intermediate in this solvolysis, it was found to hydrolyse more slowly than (46).

-

In a study of the attack of the ambident nucleophile ethanolamine on a series of phosphorylating agents (48) and related compounds 39 it was observed that the proportion of 0-phosphorylation increased as R1 and R2 varied in the series Me,N, RO, R and as X varied in the series R,PO, CN, F, this last giving exclusive 0-phosphorylation. These results were m M. M. Mhala, C. Holla, and G . Kasturi, Zndiun J . Chem., 1970, 8, 333. ' 1

'9

M. M. Mhala and S. B. Saxena, Indian J . Chem., 1971, 9, 127. B. K. Kidd, J . Chern. SOC.( B ) , 1971, 1168. R. Greenhalgh, R. M. Heggis, and M. A. Weinberg, Cunud. J . Chem., 1970, 48, 1351.

Quinquevalent Phosphorus Acids

105

interpreted on the basis of the semi-empirical treatment devised by Hudson in terms of the relative hardness of the nucleophiles and extent of charge transfer in the transition state. Surprisingly, the relative amounts of Nand O-phosphorylated products were similar to those obtained from reaction of an equimolecular mixture of propan-1-01 and n-propylamine. It',

40

/

\

MeO,

,I<'

z// P \ RZ

x Z

=

(48)

OorS

(49)

Nucleophilic attack of amines on fully esterified derivatives of phosphoric acid and its thio-analogues may in general occur at phosphorus or carbon. In an attempt to correlate the rates with structural factors, a study has been reported on a series of compounds of the type (49).40

C. Reactions.-The N-chloroquinonimine (50) reacts with monoalkyl phosphates in dry pyridine to give symmetrical pyrophosphate esters. If present in excess it can react further, giving an intermediate which is attacked by alcohols or water with cleavage of the pyrophosphate bond.

c y y

Kol'o,l!2

~

C

q

y

KOPO l i

I

0

I1 N-OP-OR I

3-

0

"'(3"

II OH

I OH

OH

0 1€

OH

0 0 ROP-0-P-OR II II

0

NOH

H,O

OR

> 2ROPO,H,

OH

Since symmetrical pyrophosphate diesters are normally rather stable compounds, (50) has been suggested as a useful reagent for cleaving naturally occurring pyroph~sphates.~~ Alkyl diary1 phosphates are converted to diesters by loss of an aryl group on treatment with potassium t - b ~ t o x i d e ,a~ ~ reaction which probably *O

4a

Nguyen Thanh T h o n g , Bull. Sac. chim. Frcirrce, 1971, 928. K . Chong, S. Pong, and T. Hata, Bull. Chem. Soc. Japan, 1970, 43, 2571. R. A. Bartsch and D. G . Wallis, J . Org. Chem., 1971, 36, 1013.

Organophosphorus Chemistry

106

involves nucleophilic attack followed by elimination. Enol dialkyl phophates are cleaved by lithium alkyls to give the lithium salt of the enol. Since these starting materials are readily accessible from Perkov reactions on a-halogenoketones, the method provides a route to enolate ions of determined Alkylation of 00-dialkyl phosphorothioates with diazoalkanes has been studied and it was observed that whereas the dimethyl ester and diazomethane gave exclusive S-methylation, increase in size of the ester groups and use of higher diazoalkanes gave considerable amounts of 0-alkylation The episulphide (51) reacted with dialkyl phosphorodithioate anions to give predominantly (52) with smaller amounts of (53).45 Triphenylphosphine or tetra-alkylammonium iodide, being powerful nucleophiles for saturated carbon, are efficient catalysts for isomerizing the esters of the type (54) to (55).46 The isomerization of the phosphorimide ester (56) to the phosphoramidic chloride proceeds extremely readily, possibly by an intermolecular S N process ~ or an intramolecular 1,3-alkyl shift.47

n

=

2or3

I1 =

2 or 3

(55)

(54) C1

I I

ArSO,N=P-OR

c1

A Et,O

Ar S0,N-POCl,

I

R

(56)

Diesters of phosphoramidic acid are converted to the corresponding isocyanates by phosgene but with N-substituted derivatives the phosphoramidic chlorides are formed.48 In a similar reaction oxalyl chloride 43 44

45

46

47 jS

I. J. Borowitz, E. W. R. Casper, and R. K. Crouch, Tetrahedron Letters, 1971, 105. M. A. Shafik, D. Bradway, F. J. Biros, and H. F. Enos, J. Agric. Food Chem., 1970, 18, 1174. 0. N. Nuretdinova, B. A. Arbusov, and F. Guseva, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 1881 (Chem. A h . , 1971,74, 64 128).

Hoang Phuong Nguyen, Nguyen Thanh Thuong, and P. Chabrier, Compt. rend., 1970, 271, C , 1465; ibid., 272, C, 1145, 1588. H. W. Roesky and W. G. Bowing, Angew. Chem. Internat. Edn., 1971, 10, 344. L. I. Samarai, 0. I. Kolodyazhnyi, and G. I. Derkach, Zhur. obshchei Khim., 1970,

40, 754.

107

Quinqirei~nlentPhosphorirs Acids

reacts with (57) to form ( 5 8 ) when R 1 = alkyl. When R1 = aryl, O-dealkylation cannot occur, and N-dealkylation leading to the isocyanate is observed."o

Trialkyl phosphates form volatile 1 : 1 adducts with acids such as nitric and chloroacetic, from which the esters are recovered by base treatment.5o 1.r. and n.m.r. spectral data suggest that these are hydrogen-bonded complexes. At low temperatures, in FS0,H-SbF,, trialkyl phosphates were shown (by n.m.r.) to give protonated species 51 in which there appears to be considerable pn-dr back-donation from oxygen to phosphorus. These species are not stable; the tri-n-butyl ester decomposing over the course of two days to Me&+ and (HO),P'-. OPSCI,

(60)

Pyrolysis of the phosphorodichloridothioate (59) at 550 "C gives mainly dibenzothiophen and a smaller amount of the cyclic phosphonochloridothioate (60).62 Thermal decomposition of di-t-butyl peroxide in triethyl phosphate gives rise to diethyl methyl phosphate 63 in a reaction which may be interpreted as resulting from attack of methyl radical on the phosphoryl oxygen. An extension of this mechanism accounts for the formation of (61) from tri-isopropyl phosphate under the same conditions. Thiophosphoryl chloride and phenylphosphonothioic dichloride give adducts with &,a'-bipyridyl and ethylenediamine, the stoicheiometry O8

L. I. Samarai, 0. I. Kolodyazhnyi, and G . I . Derkach, Zhur. obshchei Khim., 1970, 40, 944.

61

s2

W. Stec and J. Michalski, Z . Naturforsch., 1970, 25b, 554. G. A. Olah and C. W. McFarland, J. Org. Chem., 1971, 36, 1374. E. A. Chernyshev, E. F. Bugerenkov, and U . I. Aksenov, Zhur. obshchei Khim., 1'970, 40, 1423.

53

Y . A. Levin, E. K. Trutneva, I . P. Gozman, A. G. Abulkanov, and B. E. Ivanov, Izcest. Akad. Nauk S.S.S.R., Ser. khinr., 1970, 2844 (Chem. Abs., 1971, 74, 1 1 1 305).

108

0rganophosp horiis Chemistry

CH,O, Me

I

P(OPri),

4

(PriO),P=O ---+CHI C H,

0

-

CH,O,. I P(OPri ). CHO' I

C H,

depending on the particular component^.^^ Phosphoryl chloride also gives a salt-like 2 : 1 adduct with the diphosphine (62).65 The adduct is hydrolysed by water to the phosphine oxide and phosphorous acid. With thiophosphoryl chloride and (62), S-transfer occurs without the formation of an isolable intermediate. 0

PhZPCH2CH2PPhz

0 + / / + Cl2P-P-CH2CH2P-P-CI2

POCI,{

(62)

II +

/ \

Ph Ph

/ \

2Cl-

Ph Ph

2 Phosphonic and Phosphinic Acids and Derivatives

addition of Pv compounds to olefinic compounds is a well-established route to phosphonic acids, although yields are often disappointing. With phosphorus pentachloride it has been found that yields are greatly improved when phosphorus trichloride is added to the reaction mixture.5s Since the orientation of the addition implies that electrophilic addition to phosphorus rather than chlorine is the initial step, it seems likely that the trihalide participates by decreasing the free concentration of chlorine rather than by a more active role. This

A. Synthetic Methods.-Electrophilic

G4

M. Beg, A. Arshad, and M . S. Siddiquc, Pakistan J . Sci. Itid. Res., 1970, 12, 337 (Chem. A h . , 1970, 73, 56 182).

b5 66

E. Lindner and H. Beer, Chem. Ber., 1970, 103, 2802. Y. Okamoto and H. Sakurai, Bull. Cheni. SOC.Japan, 1970, 43, 2613.

Quinquevalent Phosphorus Acids

109

method has been used as a general route to p-keto-phosphonates from enol Addition of phosphorus pentachloride to dialkylacetylenes, followed by hydrolysis, has been shown to result in formation of cis-2chloroalkene-1 -phosphonic acids (63).58

PClj

RCECR

CI PCll \ / + ,C=C

R

H20

\

R

c1

\

/C=YR

R (63)

Irradiation of thiophosphoryl chloride in alkanes at 260 nm leads to the formation of phosphonothionic dichlorides (63a),5gprobably viu initial P- C1

(631)

fission followed by hydrogen abstraction by CI'. The method is convenient for introducing a phosphonyl group on to simple cycloalkanes. Conjugated dienes add to perthiophosphinic anhydrides (64) - presumably by reaction with the monomer (65) to give the cyclic ester (66)g0 which is cleaved by base treatment to give (67). S S,lt

RP,

S

,PR

s It

S

1

4 RP \

S

2-Pyridylphosphonic acid derivatives (68) have been prepared by addition of dialkyl phosphite anion to N-alkoxypyridinium salts.s1 Similar compounds, it is reported, are formed from trialkyl phosphites with li7

6R

68

OU

G. K. Fedorova, Y. P. Shaturskii, L. S. Moskalevskaya, and A . V. Kirsanov, Zhur. obshchei Khim., 1970, 40, 1167. A. V. Dogadina and B. I. Ionin, Zhur. obshchei Khirn., 1970, 40,2341. U. Schmidt and A. Ecker, Angew. Chem. Internat. Edn., 1970, 9, 458. A. Ecker, I. Boie, and U . Schmidt, Angew. Chem. Internat. Edit., 1970, 10, 191. D. Redmore, J . Org. Chem., 1970, 35, 41 14.

Orgonophosphorus Chernistry

110

N-acyl-pyridinium or -quinolinium systems 6 2 but in this case the addition leads initially to a dihydro-derivative (69), which is presumably oxidized by excess starting material. Although the detailed fate of all the reactants is not yet determined, the modest yields ( - 40%) lend support to the above

Q

0-

/

+ (Wo)?.

>-

[Q,l

N'

I OK2

f'(OR1)2

- (-1

q),{?

\N'

PO (OR

)?

(68)

I ('0

/

li (69)

view. Aminoethyphosphonic acids (70) and various substituted derivatives are readily prepared by addition of diethyl phosphite anion to various acrylamides followed by hydrolysis and Hofrnann reaction.s3 A similarly straightforward route to ar/%epoxyphosphonic acids (71) involves reaction of chloroacetaldehyde with dialkyl phosphite followed by base."* Vinyl-

R1CH=CR2CN

+

(EtO),P\= 0-

-

K'CH-CHK'CN I (EtO),P=O ( i ) t i ' 11,O (ii) Ur,-NaOlf

\

&

PO,,tI2

I RICH-CHNH? PO,H,

(70) phosphonic acid esters are formed from vinyl halides and trialkyl phosphite A similar reaction between in the presence of nickel halide ~atalyst."~ phosphorus trichloride and the aryl bromides (72) 66 with aluminium A. K. Shenkman, G. V. Samoilenko, and S. N. Baranov, Zhur. obshchei Khirn., 1970, 40, 700. J . Barycki, P. Mastalerz, and M. Soroka, Tetrahedron Letters, 1970, 3147. T. Agarai, T. Kubo, and Y. Oshiro, Synrhesis, 1971, 27. EL P. Tars and H . Weitkamp, Tetrahedron, 1970, 26, 5529. I I ~ I. Granoth, A. Khalir, Z. Pelah, and E. D. Bergmann, Israel J . Chern., 1970, 8 , 613. O3

Qiiirtquevnletit Phosphorus Aeid.y

111

chloride as catalyst and hydrolysis of the intermediate gave the corresponding arylphosphonic acid. Phosphorus tribromide reacts with nitriles to give, after treatment with acetic acid, the a-amino-diphosphonic acids (73).67

Polyphosphonic acids are conveniently esterified by treatment with orthoformate esters with distillation of the lower-boiling alcohol. This procedure worked well for the acid (74), which readily dimerizes, and was also used to establish the structure of the dimer (75).68 McC(P0,,fi2)2 I OH

(74)

M t: i i '? 0,P p O=P

/ '0'

OH

Me y PO,,H,

P=O /

OH

( 75)

B. Solvolysis of Phosphonic and Phosphinic Esters.-There has appeared over the past year a considerable amount of work on rates of nucleophilic substitution at phosphorus in phosphonate esters. In a study on the reaction of p-nitrophenyl methylphosphonate anion (76) with various amines I+@ it was argued from the observed Bransted slope of 0.35 and the solvent isotope effect k ~ , ~ /=k 1.17 ~ , that ~ nucleophilic attack of the amine on phosphorus was rate-determining (only piperidine gave any evidence of attack on the aryl ring). This view was supported by the observation that rates were very sensitive to steric effects, aziridine being much more and 2-picoline much less reactive than their respective pK,'s would suggest. A contribution from a general-base-catalysed mechanism could not be ruled out, but since the amines investigated were much more basic than p-nitrophenate ion, such a contribution should not be large. With other nucleophiles 70 it was found that, as with similar phosphate esters, there is a H7

HR

'O

0. Lukevic and L. Maijs, Latc. P.S.R. Zinat. Akad. Vestis., Khim. Ser., 1970, 732 (Chem. Abs., 1971, 74, 42 428). D. A. Nicholson, W. A. Cilley, and 0. T. Quirnby, J . Urg. Chem., 1970, 35, 3149. H. J. Brass, J. 0. Edwards, and M. J. Biallas, J. Atner. Chem. Soc., 1970, 92, 4675. E. J. Behrman, M. J. Biallas, H. J., Brass, J. 0. Edwards, and M. Isaks, J . Urg. Cherrz., 1970,35, 3063, 3069.

112

Organophosphorus Chemistry

large a effect, with peroxide, hypochlorite, and oxime anions being the most reactive. Unexpectedly, thiophenoxide reacted faster (50 times faster) than phenoxide ion, as opposed to the expected order. In contrast, the solvolysis of sarin (77) with a series of amines 71 proceeds by a general-base mechanism for nitrogen nucleophiles but by a nucleophilic mechanism for oxygen nucleophiles. For the former there were no discrepancies in the linear free-energy plot (Brsnsted slope 0.50) and no appreciable a effect was observed.

Gels of yttrium hydroxide are powerful catalysts for the hydrolysis of (76), and it was suggested7, that the hydroxide acts as a bifunctional general acid and nucleophile. The fact that gels of transition-metal hydroxides do not show comparable activity was attributed to their fixed co-ordination number, resulting in more rigid stereochemistty. In the pH range 2-3.5 the phosphonate (78) hydrolyses with loss of ROH at approximately lo7 times the rate of comparable esters lacking the vicinal oxime function 7 3 or in which this function is methylated on oxygen. An intramolecular general-acid catalysis mechanism was proposed, but it was not possible to exclude entirely an intramolecular nucleophilic attack at phosphorus. Intramolecular attack by the vicinal dimethylamino-group takes place preferentially at carbon rather than phosphorus in the phosphonofluoridate (79).74 M c.,

In the solvolysis of a series of derivatives of phosphetan-1-oxide (80) it has been observed that, when X = NMe, or C1, rates were lower than for comparable acyclic analogues 7 5 whereas when X = OR the converse was true. Making the assumption that all these displacements proceed by way 71 7R

"' 74 75

J . Epstein, J. R . Sowa, and P. I-. Cannon. .I. Anrcr. Clierii. Soc., 1970, 92, 7390. F. McRIewctt and P. Watts, J. Cheni. Soc. ( B ) , 1971, 881. J. I. Ci. Cadogan and D. T. Eastlick, Chrm. Conrni., 1970, 1546. El. P. Renschop, G. R. Van den Berg, and C i . W. Kray, Re!?.Trao. chin)., 1970,89, 1025. P. Haake, R. D. Cooke, T. Koizurni, P. S. Ossip, W. Schwartz, and L). A. Tyssce, J . Amer. Chetn. Soc., 1970, 92, 3828.

Quinquevalent Phosphorus Acids

113

of a trigonal-bipyramidal intermediate (in which the ring spans one apical and one basal position) and that entering and leaving groups take up apical positions, it is seen76 that initial attack necessarily places X basal (81).

Since more electronegative groups preferentially occupy apical positions when X is strongly electronegative (C1 or NHMe,), this may be less favourable than the acyclic case where there is no constraint on the two alkyl groups. On this view it is predicted that when X is strongly electronegative substitution should proceed with retention of configuration whereas when X and R have comparable electronegativities the alternative pseudorotation leading to inversion may be favoured. A similar argument has been invoked to account for racemization on the alkaline solvolysis of the ester (82),77 since it was shown that neither the starting material nor S

/I ot I ~ ~ p - s p ___ ~ i

S

II

the product underwent racemization under the conditions. With a relatively poor leaving group (and the less electronegative one) it is reasonable to assume that a pentacovalent intermediate may undergo sufficient pseudorotations to result in racemization prior to breakdown to the product. The authors suggest that reactions assigned metaphosphate-type intermediates on the basis of stereochemical evidence may in fact proceed by a pentacovalent intermediate, but this view is inconsistent with the very large rate enhancements observed in these latter cases. The rate of solvolysis of the phosphinic chlorides (83a, b) in trifluoroacetic acid and aqueous acetone (the composition of the latter solvent being chosen such that the rate of SN1 solvolysis of ButCl was the same in both) have been examined 7 8 to assess the possible operation of an SN~(P) ionization mechanism. In the more nucleophilic aqueous acetone solvent,

'* J. R. Corfield, N. J . De'ath, and S. Trippett, Chem. Cornm., 1970, 1502. L. P. Rieff, L. J . Szafraniec, and H . S. Aaron, Chem. Comm., 1971, 366. '" P. Haake and P. S. Ossip, Terrahedron Letters, 1970, 4841.

''

1 I4

Organophosphorirs Chemistry

(83a) solvolysed 2000 times faster whereas (83b) solvolysed at only twice

the rate, indicating a large degree of &I(P) character in the latter. Nevertheless, no direct evidence for the formation of phosphinylium ions from dialkylphosphinic acids could be obtained even in oleum.

The basicities of some phosphinamides (84) have been measured and the acid-catalysed hydrolysis Unsubstituted and N-alkyl derivatives follow an A 2 mechanism of reversible protonation followed by ratedetermining water attack. However, the rates for the N-aryl derivatives follow H , (but with a slope of OS), and an A1 mechanism was suggested as most consistent with this fact and the solvent isotope effect. The anomalous dependence on H,, together with the large negative value of AS*, while not necessarily excluding an ionization mechanism, leaves the question in some doubt. Phosphonoformic acid (85) decarboxylated in acid solution, and it was proposed that the uncatalysed reaction involved a simple decarboxylation of the zwitterion. The acid-catalysed reaction showed some kinetic similarity to that of mesitoic acid and an elimination of carbon dioxide as trihydroxymethylcarbonium ion was preferred. Participation of the trans vicinal phosphonyl group in the solvolysis of the halides (86) and (87)R1 has been deduced from rate measurements. In the norbornene derivatives, the relative rates of loss of chloride from (87a) and (87b) were 5 x lo4 : 1.

-

Cl (873)

(571))

Rates of hydrolysis of a series of phosphonochloridate esters (88) have been measured and some general deductions on the effect of variation of R1 and R2 on the rates have been proposed.82 An attempt to correlate the 70

n2

P. Haake and T. Koizumi, Tetrahedron Letters, 1970, 4845, 4849. S. Warren and M . R. Williams, J . Chem. SOC.( B ) , 1971, 618. C. E. Griffin, Colloq. Int. Cent. Nut. Rech. Sci., 1970, 182, 95. A. A. Neimyshiva, M. V. Armolaeva, and I. L. Knunyants, Zhur. obshrhei Khim., 1970,40, 798.

Qiiinqir ei.alen t Pliosp ho r irs A c i h

115

rates of solvolysis of a series of P-F compounds with the calculated energies of the lowest unfilled orbitals has met with a fair degree of success.83 The rates of neutral and basic hydrolysis of a series of esters of (chloroalky1)phosphonic acids (89, n = 1, 2, or 3) have been measured, and it was claimed that when n = 2 the alkaline hydrolysis was assisted by the halogen.84 However, the rate enhancement was small ( 10 times) and it is possible that elimination to the vinyl phosphonic ester may also be occurring.

-

cI(CH,),,PO(OR),

C. Reactions of Phosphoric and Phosphinic Acid Derivatives.-The optically active phosphinate ester (90) has been shown to react with benzyl Grignard reagents or lithium anilide with inversion of configuration.s6 Oxidation of (91) and (92) with N-chlorosuccinimide leads to the corresponding acid chlorides,86the reaction proceeding more rapidly with (92). Unlike the compound (91), whose oxidation may be stereospecific, the oxidation of (92) results in extensive racemization.

R

- 7

nienthyl, cholc\tcryl (90)

(91) X (92) X

-=

0

1

S

Phosphinate esters may be converted to the P=S analogues, with retention of configuration, by phosphorus p e n t a ~ u l p h i d e86. ~ ~The ~ converse transformation (93) to (94) may be brought about by oxidation with nitric acid or dinitrogen tetroxide, the former giving inverted product with a high degree of stereospecificity while the latter gives retention with racemizat i ~ n . ~ ~

R6

”’

M. A. Landau, V. V. S. Sheluchenko, and S. S. Duba, Zhur. strukt. Khim., 1970,11, 513 (Chem. A h . , 1970, 73, 65 601). V. E. Belskii, M. V. Efremova, and V. N . Eliseenkov, Izuest. Akad. Nauk S . S . S . R . , Ser. khim., 1970, 561 (Chem. Abs., 1970, 7 3 , 73 747). A. Nudelrnan and D. J. Cram, J . Org. Chem., 1971, 36, 335. L. J. Szafraniec, L. P. Rieff, and H. S. Aaron, J . Amer. Chem. Sac., 1970, 92, 6391. J. Michalski and A. Okruvszak, Chem. Comm., 1970, 1495.

116

Organophosphorus Chemistry

Esters of a-diazoalkylphosphonic acids ( 9 5 ) show considerable thermal stability but react with acids, dienophiles, and triphenylphosphine to give the expected products.** With olefinic compounds in the presence of copper they give cyclopropane derivatives (96), but with no such compounds present vinylphosphonic esters are formed by I ,2-hydrogen shift, or, when this route is not available, products such as (97) or (98)R9are formed, resulting from insertion of a carbenoid intermediate into C-C or C-H bonds. The related phosphonyl (and phosphoryl) azides (99) add to electron-rich alkynes to give 1,2,3-triazole~,~~ from which the phosphoryl group is readily removed by hydrolysis. tic I

R'CN,

I PO(OR')?

---+ R1CHCIPO(OK2).)

M c But

But \ ,c=c / H Me 'C PO (OMe), N2

(99) Hs

"B

1.CU

PO(Ohlc):!

Et,N'

Me

D. Seyfcrth, R. S. Marmor, and P. Hilbert, J . Org. Chem., 1971, 36, 1379. D. Seyferth and R. S. Marmor, J . Org. Chcm., 1971, 36, 128. K. D. Berlin, S. Rengaraja, and T. E. Snider, J . Org. Chem., 1970, 35, 2027.

Qi!inyuei~aletttPhosphorus Acids

117

Diazoalkanes add readily to the double bond of esters of vinylphosphonic acid, giving the pyrazoline derivatives (loo), which can lose nitrogen to give esters of cyclopropylphosphonic acids.B1 In a similar reaction, acylphosphonic acid esters (101) were converted to epoxy-derivatives (1 02p2 N-Phenylsydnone adds to diethyl prop- 1 -ynephosphonate, giving the pyrazole (103).B3The addition of cyclopentadiene to dimethyl vinyl phosphate leads to an exolendo quotient of 1.2, but with hexachlorocyclopentadiene only endo-isomer is formed.g4

0 ( R10),P4*

PI1 S ’ N ,

‘C?

Ph

R2 (101)

I I’ll

The Schmidt reaction of diesters of (substituted-benzoyl) phosphonic acid (104) leads to the result that, when Ar = p-chlorophenyl, 90% of the reaction proceeds by aryl migration, whereas when Ar = p-anisyl (generally considered a better migrating group) only phosphoryl migration was This is consistent with the assumption that it is the group best able to stabilize the developing positive charge on that carbon atom which does not migrate.

92

99

O4

A. N. Pudovik, R. D. Gareev, and 0. E. Raevskaya, Zhur. obshchei Khim., 1970, 40, 1189. A. N. Pudovik, R. D. Gareev, and L. A. Stabrovskaya, Zhur. obshchei Khim., 1970, 40, 698. A. N. Pudovik and N. G. Khusanova, Zhur. obshchei Khim., 1970, 40,697. H. Callot and C. Beneza, Canad. J . Chem., 1970, 48, 3382. D. Kost and M. Sprecher, Tetrahedron Letters, 1970, 2 5 3 5 .

5

118

Organophosphorus Chemistry

(lox)

(107)

S

S II ,s\

RI’,

11J. - 0 - 1 ’

c‘t 1,OJ I

+ hlclC/

,PI< s 5I!

+

1

c‘€1,0 t €

II , I t

\ / S I S \ / HA<’--0- I’

Ilc,I’

(W

I! \I< S (

100)

Reaction of perthiophosphonic anhydrides (64) with amines go leads first to (105) and then, by further attack, to (106). With ammonia itself the second addition proceeds at the same phosphorus atom as the initial attack, giving (107) and (108). The anhydride (64) is also reported to react with 1,3-diols to give cyclic phosphonyl disulphides (109).87 Thermal decomposition of phenylphosphinic anhydride (1 10) may lead to the formation of PhP since in the presence of benzil the formation of the phosphorane (1 1 1) was observed.gn PI1

0 It I’ll

O7

O8

-

1’I

0

I1

0- I> --P h I

l’11-1’--0

0’ ‘0

1

El,,,, _j

( I 12) ( 1 13) ( I 14) E. Fluck and H. Binder, 2. anorg. Chem., 1970, 377, 298. P. N. Grishina. L. M. Kosova, I. P. Lipatova, and R. R. Shagidullin, Zhur. obshchei Khim., 1970, 40, 6 6 . M . J. Gallagher and I. D. Jenkins, J . Chem. Sac. ( C ) , 1971, 593.

Quinquevalent Phosphorus Acids

I19

Irradiation of I-azidophosphetan-I-oxide(1 12) in methanol leads to the phosphonamide esters (1 13) and ( I 14),gn although the stereochemistry of these products is not yet fully settled. Their formation is reasonably consistent with the intervention of a nitrene intermediate which inserts into the P-C and C-H bonds. The rate of reaction of phenylmagnesium bromide with a series of phosphorus esters fell along the series: Ph,PO(OEt) > PhPO(OEt), > Et,PO(OEt) > EtPO(OEt)2 > (EtO),PO attributed to increasing loss of p-d bonding energy on proceeding from a tetrahedral state to a trigonalbipyramidal intermediate.loO 00-Diethyl phenylphosphonothioate did not react with the Grignard reagent but several phosphonothioic chlorides do, and this latter reaction has been used to prepare some sterically hindered phosphine sulphides.lO1 The cyclic phosphonate (1 15) is hydrolysed in acid with loss of MeOH whereas in basic solutions ring-opening occurs almost exclusively -- a result in accord with the greater restriction on pseudorotation in a pentacovalent intermediate under basic conditions.

hi u ( 1 15)

(lI6)X (117)X

=--

0

s

The phosphinic isocyanates (1 16) lo3 and isothiocyanates (1 17) lo4 react with oxygen, nitrogen, and phosphorus nucleophiles by attack at carbon rather than phosphorus. Phenyl phosphonodichloridate has been recommended as a useful reagent for the activation (presumably by mixed anhydride formation) of carboxylic acids for conversion to amides and h ydrazides. lo6 3 Miscellaneous

Conformation problems in five- and six-membered rings containing phosphorus continue to attract attention and, using n.m.r., i.r., and dipole-moment measurements, studies have been reported on 1,3,2dioxaphospholan systems (1 1 8),lo6~ I ,3,2-dioxaphosphorinane systems M. J . P. Harger, Chem. Contm., 1971, 442. H. R. Hays, J . O r g . Chern., 1971, 36, 98. G. Hagele and W. Kucher, Chem. Ber., 1970, 103, 2885. l o a N. I. Rizpolochenskii, F. S. Mukhametov, and Y . Y . Samilov, Izuesf. Aknd. Nouk. S.S.S.R., Ser. khim., 1970, 910 (Chem. Abs., 1970, 73, 35 451). l o s L. I . Samarai, 0. I. Kolodyazhnyi, 0. V. Vishnevskii, and G . I. Derkach, Zhur. obshchei Khini., 1970, 40,754. G . Tomashiewski and Z. Dieter, 2. Chem., 1970, 10, 117. l o b G. Baccolini and G. Rosini, Chimica e Ittdiisrrio, 1970, 52, 583, (Chem. Abs., 1970, 73, 55 777). l o o K . Bergeson, Acfa Chem. Scnnd., 1970, 24, 1122. A. Bousquet and J. Navech, Compr. rend., 1971, 272, C , 246; M. Revel and J . Navech, Compt. rend., 1971, 272, C, 700. no

loo

120

Organophosphorus Chemistry

( I 19),loe-l1O 1,3,2-diazaphospholidine systems (1 20),Io7 and the phosphorinane (1 21).11’ The temperature variation of the JPOC.H spin-spin coupling constants has been used to determine the most stable conformations of trineopentyl phosphate and tris(2-chloroethyl) phosphates.l12

x -0.s I<

I

C‘I, OR, NMc, ( 120)

Detailed interpretations of the n.m.r. spectra of vinylphosphonic acid,l13 p h o s p h o e n ~ l p y r u v a t e ,and ~ ~ ~ some N-phosphorylaziridines have been carried out. The vibrational spectra of ethyl phosphorodichloridate and its 1,l -dideuterio- and 2,2,2-trideuterio-derivativeshave been examined.lls Solvent effects on the magnitude of spin-spin coupling constants in phosphoryl compounds have been reported,lf7 as have the solvent effects on the relative strengths of phosphoric acid and some of its partially esterified derivatives.ll* The variation of i.r. frequencies of (1 22) and (1 23)

llS

C. L. Bodkin and P. Simpson, J . Chem. SOC.(B), 1971, 1136. J.-P. Majolal and J. Navech, Bull. SOC.chim. France, 1971, 95. B. A. Arbusov and R. N. Arshirova, Doklady Akad. Nauk S . S . S . R . , 1970, 195, 835 (Chem. A h . , 1971, 74, 87220). K. Bergeson and A. Bergl, Acta Chem. Scand., 1970, 24, 1844. A. A. Bothner-By and W. P. Trantwein, J . Amer. Chem. SOC.,1971, 93, 2189. T. N . Timofeeva, B. V. Semakov, and B. I. Jonin, Zhur. obshchei Khim., 1970, 40,

11’

M.Cohn, J. E. Pearson, E. L. O’Connell, and I. R. Rose, J . Amer. Chem. SOC.,1970,

lo8 loo

Ila

1169.

ll@

11’ 118

92, 4095. K. D. Berlin, S. Bengaraja, and P. E. Clark, J . Heterocyclic Chem., 1970, 7, 1095, 1215. R. A. Nyquist, W. N. Muelder, and M. N. Wass, Spectrochim. A d a , 1970, 26A, 769. L. I. Vinogradov, Y. Y. Samitov, and A. T. Kessel, Teor. i eksp. Khim., 1970, 6, 103 (Chem. Abs., 1970,73, 55 261). N . Molchanova and V. I. Dulova, Zhur. j z . Khim., 1970,44, 1542 (Chem. A h . , 1970, 73, 55261).

121

Quinquevalent Phosphoriis Acids

on changing the solvent from carbon tetrachloride to deuteriochloroform ll9 is well in accord with the greater basicity of the latter. Quantitative studies on the hydrogen-bonding between HMPA and chloroform have been reported,120 as has an investigation into the mutual solubilities of methyl diphenyl phosphate and aliphatic hydrocarbons.121

(KS),PO 122)

( R N ) P0

( I 23)

0 II MeP -OPr I H ( 1 24)

Cycloamylose forms inclusion complexes stereoselectively with the enantiomers of isopropyl methylphosphinate (124) from which it was possible to isolate one enantiomer with an optical purity of 66%.122The absolute configuration of menthyl methylphosphinate has been revised 123 to the opposite of that previously assigned. 'lo

12?

0.G.Strukov, S. S. Dubov, and M. A. Landan, Zhur. sfrukt. Khim., 1970, 11, 148 (Chem. A h . , 1970, 73, 44 717). T. Olson, Acta Chem. Scand., 1970, 24, 3801. A. Apelbat, J . Chem. SOC.(B), 1970, 1459. H. P. Benschop and G . R. Van den Berg, Chem. Comm., 1970, 1431. W. B. Farnham, R. K. Murray, and K. Mislow, Chem. Comm.,1971, 605.

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

1 Mono-, Oligo-, and Poly-nucleotides A. Mononuc1eotides.-A new journal has appeared in the past year consisting of abstracts of papers published in the nucleotide and nucleic acid fields.’ The use of nucleosides and nucleotides as potential therapeutic agents has been reviewed.2 Nucleotides which have been prepared recently using conventional methods of phosphorylation include those derived from 6-methylthiopurine ri bonucleoside (1 a),3 5-methylsulphonyluridine ( I b),4 1-(p-~-ri bofuranosyl)-2-pyrimidone ( I c ) , ~ 3-(p-~-ribofuranosyl)-4pyrimidone (1 d),5 and various thionucleosides.6e’ 0-Phosphorylated 3’-amino-3’-deoxythymidine (2a) and 5’-amino-5’-deoxythymidine (2b)

Nl12 (?a)

’

0 I’o:i II (2173

Nircleic Acids Abstracts, Information Retrieval Ltd., London. T. Y . Shen, Angew. Chem. Inferrrat. Edn., 1970, 9, 678. F. Perini and A. Hanipton, J. Heterocyclic Chem., 1970, 7 , 969. J. M. Carpenter and G. Shaw, J. Chem. SOC.( C ) , 1970, 2016. H. Pischel and A. Holg, Coll. Czech. Cherri. Cortzrn., 1970, 35, 3584. P. Faerber and K. H. Scheit, Chem. Ber., 1971, 104, 456. S. Irie, J. Biochem. (Jctpan), 1970, 68, 129.

Phosphates and Pliosphnnntcs of’Biochemical Ititerest

I23

have been synthesised by reduction of the corresponding azidonucleotides,* and 5’-amino-5’-deoxy-analogues of 3’,5’-cycIic-AMP* have been prepared.O 4-Nitrophenyl esters of thymidine are substrates for staphylococcal nuclease lo and ribonucleotide 5’-(5-iodoindol-3-ol) (3) and 5’-(4-methylcoumarin-7-01) (4) esters have been used for the histochemical demon-

I

II

(3) nkrc K

(4) -

.5’-riboniic.lec,tidc

stration of nucleases.ll Enzymatic hydrolysis of (3) results in the formation of an insoluble, electron-dense 5,5’-di-iodoindigo dye, while hydrolysis of (4)liberates a fluorescent coumarin. When A M P is heated under reflux in DMF, the 2’,3’-cyclic phosphate is formed,12and cyclic phosphates can also be obtained from nucleosides and ortho-, pyro-, or poly-phosphoric acids under the same conditions. Promotion of phosphorylation by DMF is well known l3 and the reaction with AMP is probably intermolecular as no 3’,5’-cyclic A M P can be detected. Minor products in the latter reaction are the 2’,3’-cyclic 5‘-diphosphate and the 2’(3’),5’-diphosphate. The synthesis of adenosine 2’(3’)-phosphate 5’-pyrophosphate has been achieved 14n by the phosphoromorpholidate method used in a synthesis of CoA.l4* Any discussion of the prebiotic phosphorylation of nucleosides must take into account the probably neutral or alkaline conditions in a prebiotic environment.15 Some model phosphorylating systems have been studied, for example, the synthesis of @-ri bofuranose 1-phosphate from ribose and inorganic phosphate in the presence of cyanogen.le Sodium trimetaphosphate will phosphorylate cis-glycols in good yield under alkaline R. P. Glinski, M. S. Khan, R. L. Kalamas, C. L. Stevens, and M. B. Sporn, Chem. Cotnm., 1970, 915. A. Murayama, B. Jastorff, and H. Hcttler, Angew. Chem. Internat. Edn., 1970, 9 , 640. l o R. P. Glinski, A. B. Ash, C. L. Stevens, M. B. Sporn, and H. M. Lazarus,J. Org. Chem., 1971, 36, 245. L. C. March and K. C. TSOU,J . Heterocyclic Chetn., 1970, 7 , 885. T. Ueda and 1. Kawai, Chern. andPharm. Bull. (Japan), 1970, 18, 2303. F. Cramer and M. Winter, Chem. Ber., 1961, 94, 989; F. Cramcr, S. Rittner, W. Reinhard, and P. Dcsai, Chem. Ber., 1966, 99, 2252. Y. Hosokawa, Y. Yotsui, 0. Nagase, and M. Shimizu, Chem. andPharm. Bull. (Japan), 1970,18, 1052; J. G. Moffatt and H. G. Khorana, J . Amer. Chetn. Soc., 1961, 83, 663. l6 R. M. Lemmon, Chetn. Reo., 1970, 70, 95. l6 M. Halmann, R. A. Sanchez, and L. E. Orgel, J. Org. Chern., 1969, 34, 3702; C. Degani and M. Halmann, J. Chem. Soc. (C), 1971, 1459. * Abbreviations uscd in this chaptcr for biochemical compounds may be found in the Instructions to Authors of the Biochetnical Journul. (L

124

Organophosphorus Chemistry

conditions.l7* The formation of nucleotides in the reaction between nucleosides and basic or neutral inorganic phosphates at 65-100 “C in the presence of urea has been recently reported.In Hydroxyapatite will function as a phosphorylating agent under these conditions, and the reactive species could be an imidoyl phosphate. When cyanoacetylene (9,which is produced when an electric discharge is passed through a mixture of methane and nitrogen,20 is dissolved in a phosphate buffer a stable enol-phosphate (6) is formed.21 Pyrophosphate is produced when neutral aqueous solutions of (6) and orthophosphate are heated, and the phosphorylation of U M P has been achieved. However, from a study of the rate of phosphorylation and a consideration of environmental factors, especially the likely phosphate concentration i n oceans, it is suggested that (6) is not an important intermediate in prebiotic phosphorylation. The conversion of the 3’-phosphate of 02:2’-cyclocytidine (7) into 2’,3’-cyclic C M P under mild conditions in aqueous solution has

NH

HO ( 7)

been put forward 22 as a possibility for the prebiotic formation of cytidine nucleotides, and conditions have been found in which there is little or no formation of the am-nucleotide. The 5’-phosphate and 3’,5’-diphosphate of (7) can be prepared from CMP and partially hydrolysed phosphorus o x y c h l ~ r i d e . ~Phosphoribosyl ~ transfer from pyrimidine nucleotides to purines occurs at elevated temperatures24 and this reaction may be of interest as a possible method for the prebiotic formation of nucleotides. Another prebiotic source of nucleotides may be the phosphorylation of nucleosides by neutron-activated ~ i l i c a t e s . ~ ~ W. Feldman, Chem. Ber., 1967, 100, 3850. R. Saffhill, J . Org. Chem., 1970, 35, 2881. R . Lohrmann and L. E. Orgel, Science, 1971, 171, 490. 2 o R . A. Sanchez, J . P. Ferris, and L. E. Orgel, Science, 1966, 154, 784. 21 J. P. Ferris, G. Goldstein, and D. J. Beaulieu, J . Amer. Chem. SOC.,1970, 92, 6598. aa C. M. Tapiero and J . Nagyvary, Nature, 1971, 231, 42. *s T.Kanai and M . Ichino, Tetrahedron Lerters, 1971, 1965. 2 4 M. Miyaki, A . Saito, and B. Shimizu, Chem. and Pharm. Bull. (Japan), 1970, 18, 2459, 26 M . Akaboshi, K . Kawai, and A. Waki, Biochirn. Biophys. Acta, 1971, 238, 5 . la

Phosphates and Phosphonates of Biochemical Interest

125

Ri bonucleoside 5’-O-hydroxymethylphosphonates (8 ; R = OH) are resistant to the action of phosphatases and phosphodiesterases. They are, however, good substrates for snake venom 5’-nucleotidase, unlike (8; R = H).26 Isosteric phosphonate analogues of nucleoside 3’- (9) 27 and 5’-phosphates (10) 28 have been prepared using the reaction between stabilized carbanions and ketosugars. The synthesis of (10) is comparatively simple as nucleoside

(9)

5’-aldehydes are readily accessible;28 however, the instability of 3’-ketonucleosides under basic conditions renders the synthesis of (9) more difficult. The key step in the preparation of (9) was the condensation of (11) with a chloromercuri-salt of a purine. Intramolecular cyclization of (10; B = adenosine) gave the analogue of 3’,5’-cyclic AMP (12). Analogues of nucleoside 2’,3’-cyclic phosphates (1 3) and dinucleoside phosphates derived from both (9) and (10) have also been made.29

Attention has been drawn to the potential of phosphoric acid anhydrides of nucleoside 5’-carboxylic acids (14) as specific reagents for investigating the binding sites of enzymes.3o For example, (14; B = adenosine) inactivates adenylosuccinate lyase from E. coli almost completely, but has little effect on rabbit muscle AMP deaminase. The rate of hydrolysis of (14) is considerably faster than that of acetyl phosphate, suggesting intramolecular assistance by the 3‘-hydroxyl group or the 3-nitrogen atom. z‘ z7

as

**

3O

A. Holy and N. D. Hong, Cull. Czech. Chem. Cumm., 1971, 36, 316. H. P. Albrecht, G. H. Jones, and J. G . Moffatt, J . Amer. Chem. Soc., 1970, 92, 5511. G . H. Jones and J . G . Moffatt, J . Amer. Chem. Suc., 1968, 90, 5337. G . H. Jones, H. P. Albrecht, N. P. Damodaran, and J. G. Moffatt, J . Amer. Chem. SOC.,1970, 92, 5510. A. Hampton and P. J. Harper, Arch. Biochem. Biuphys., 1971, 143, 340.

126

Organophosphorits Chemistry

The association between RNase A and 3’-UMP or 3’-dUMP has been studied by 31P r ~ . m . r . ~ and l kinetic respectively. In both cases the participation of two dissociable groups at the active site of the enzyme was demonstrated, in agreement with ‘H n . r n . ~ -and . ~ ~ X-ray 35 studies on the binding of 3’-CMP to RNase. In the binding of TI RNase to purine nucleotide nionophosphates, the phosphate group appears to have an important effect while the ribose ring is relatively ~ n i m p o r t a n t . ~ ~ The sequential removal of single residues from the 3’-OH end of polyri bonucleotides is extensively used in the determination of their structure.3’ For example, oxidation of the cis-glycol function at the 3‘-OH end of the polynucleotide with periodate can lead to elimination of the terminal nucleo~ide.~ The ~ latter reaction is promoted by primary amines, and phosphate release which occurs at a maximum rate around neutrality is dependent on amine concentration. While the nucleoside fragment formed by elimination of phosphate has not been isolated, a difference spectrum has been obtained which suggests the presence of a C=C-C=N ~ h r o m o p h o r e .The ~ ~ carbinolamine (1 5 ) is probably formed initially and then loses water to give the Schiff base (16). Elimination of phosphate from (16) can occur following removal of the 4’-proton by excess amine. This reaction is the basis of a chemical method for the specific cleavage of tRNAs at 7-methylguanosine residues.3B Alkaline treatment of the tRNA opens the five-membered ring of 7-MeG to give (17); cleavage of the nucleic acid occurs when this is treated with aniline under mildly acidic conditions. Presumably the aldehyde (18) is an intermediate in this reaction. 341

31 33 s3

s4 s6

37 3R

:I8

G . C. Y . Lee and S. I . Chan, Biochent. Biophys. Res. Cornm., 1971, 43, 142. F. G. Walz, jun., Biochemistry, 1971, 10, 2156. D. H. Meadows, ti. C. K. Roberts, and 0. Jardetsky, J . Mol. Biol., 1961, 45, 491. G. B. Kartha and D. Harker, Nufirre, 1967, 213, 862. H. W. Wyckoff, K. D . Hardman, N . M . Allewell, T. Inagami, L. N. Johnson, and F. M. Richards, J . Biol. Chem., 1967, 242, 2398. M. K. Campbell and P. 0. P. Ts’o, Biochim. Biophys. Acto, 1971, 232, 427. P. T. tiilham, Ann. Reg. Biochent., 1970. 39, 226. A . Stcinschneider, Biochernisrry, 1971, 10, 173. W. Wintermeyer and H . G . Zachau, F.E.B.S. L e / / r r s , 1970, 1 1 , 160.

Phosphates and Phosphonates of Biochemical Interest

T

O I

I Yf

127

A

0

Me

0

B. Nucleoside Po1yphosphates.-In a critical discussion, the role of the ~~ 'high energy phosphate bond' in ATP in viuo has been q ~ e s t i o n e d .The concept of the 'high energy bond' is only appropriate for a closed system containing energy-linked reactions, and since living organisms are not closed systems in the thermodynamic sense, the direction of flow of matter through any individual metabolic step cannot be predicted from standard free energy data. GTP is an essential component in protein synthesis, and it has been shown recently that another guanosine polyphosphate, guanosine 3',5'40

B. E. C . Banks and C . A. Vernon, J . Theoret. Biol.,

1970, 29, 301.

128

Organophosphorus Chemistry

dipyrophosphate lppGpp (1 9)] inhibits the transcription of bacterial ribosomal RNA genes by interaction with one of the transcription Several analogues of GTP have been used in the past to study the role of GTP in protein synthesis. For example, guanylyl 5’-methylenediphosphonate (20) is a competitive inhibitor in polypeptide ~ y n t h e s i s , ~ ~ and it appears that the cleavage of the fl-y phosphate groups in GTP is necessary for peptide fo~mation.‘~This is supported by the observation 44 that guanylyl 5’-phosphohypophosphate (21) is a competitive inhibitor in polypeptide synthesis. 8-Bromo-GTP, which is presumably in the synconformation (22),46 has little activity in protein synthesis 46 as the altered 0

0 0

HO OH

0

conformation of the polynucleotide probably renders it incompatible with the binding site of the enzyme. Diguanosine 5’-tetraphosphate 4 7 and 5’-triphosphate4*are known to occur in the underdeveloped eggs of the brine shrimp (Arfemia salina) and have been located in the embryos of this organism.4e These polyphosphates may play an important part during morphogenesis and differentiation of Artemia. 41

42

13 44

A. A. Travers, R. I. Kamen, and R. F. Schlief, Nature, 1970, 228, 745. J. W. B. Hershey and R . E. Monro, J . Mol. B i d . , 1966, 18, 68. J . W. B. Hershey and R . E. Thach, Proc. N o t . Acad. Sci. U.S.A., 1967, 57, 759. P. Remy, M. L. Engel, G. Dirheimer, J. P. Ebel, and M. Ravel, J . Mu/. B i d . , 1970,

48, 173. S. S. Travale and M . Sobell, J . Mol. B i d . , 1970, 48, 109. H. Uno, S. Oyabu, E. Ohtsuka, and M . Ikehara, Biochitpt. Biophys. Acto, 1971, 228, 282. (’ A . H . Warner and F. J. Finamore, Biochim. Biophys. Acta, 1965, 108, 525. 4u F. J. Finamore and A. H. Warner, J . B i d . Chem., 1963, 238, 344. 48 A. Sillero and S. Ochoa, Arch. Biochem. Biophys., 1971, 143, 548. 45

Phosphates and Phosphonates of Biochemical Interest

129

Adenosine 5’-hypophosphate (23), an analogue of ADP, can undergo phosphorylation by PEP and pyruvate kinase to yield (24).50 Adenylate kinase which catalyses the scission of the bond between the 01 and 18 phosphorus atoms in ADP is, not surprisingly, inhibited competitively by (23). 00 \\ II

AdOPP(OI1), 1

+ PEP

pyru\ntc hinase

,

1-10

00 0

\\I1 II AdOPPOP(OH), / I 1 4 0 OH

(23)

(24) uhcrc Ad

-

ndcnocinc-5’

C. Oligo- and Poly-nuc1eotides.- - The stepwise enzymatic synthesis of internucleotide bonds has been reviewede51 A number of polynucleotides containing modified bases have been synthesised52-55 in the past year from nucleoside triphosphates with the aid of a polymerase enzyme, and the enzymatic synthesis of oligodeoxyribonucleotides using terminal deoxynucleotidyl transferase has been studied.66 Primer-independent polynucleotide phosphorylase from Micrococcus luteus has been attached to cellulose after the latter has been activated with cyanogen bromide.67 The preparation of insolubilized enzyme has enabled large quantities of synthetic polynucleotides to be made. The soluble enzyme has been used to prepare various modified polycytidylic acids.S**6* In the synthesis of polynucleotides with soluble polynucleotide phosphorylase the products are generally homogeneous in size. In a recent study,60it was suggested that elongation of the polynucleotide takes place without dissociation of the growing chain from the enzyme as no oligonucleotides could be detected in the reaction mixture. This suggestion is supported by electron microscopy which shows the presence of cocoon-li ke enzyme molecules during the polymerization reaction.61 Apparently, the polymer can coat the entire enzyme before it is released on completion of the chain. J. Setondji, R. Remy, J. P. Ebel, and G. Dirheimer, Biochim. Biophys. Acta, 1971, 232, 585. 61 S. M. Zhendarova, Russ. Chem. Rev., 1970, 39, 695. 62 G. F. Gerard, F. Rottman, and J . A. Boezi, Biochemistry, 1971, 10, 1974. 63 F. Cramer, E. M. Gottschalk, H. Matzura, K. H. Scheit, and H. Sternbach, European J . Biochenr., 1971, 19, 379. J. Smrt, Coll. Czech. Chem. Comm., 1970, 35, 2314. ss K. Ikeda, J. Frazier, and H. T. Miles, J. Mol. Biol., 1970, 54, 59. 6e L. M. S. Chang and F. J . Bollum, Biochemistry, 1971, 10, 536. b7 C. H. Hoffmann, E. Harris, S. Chodroff, S. Michelson, J. W. Rothrock, E. Peterson, and W. Reuter, Biochem. Biophys. Res. Comm., 1970, 41, 710. 6n J. Smith, P. Strehlke, U. Niedballa, H. Vorbriiggen, and K. H. Scheit, Biochim. Biophys. A m , 1971, 228, 654. D. B. Ludlum, Biochim. Biophys. Acta, 1970, 213, 142. 6 O M. N. Thang, R. A. Harvey, and M. Grunberg-Manago, J. Mol. Biol., 1970, 53, 261. O1 R. Valentine, M. N. Thang, and M. Grunberg-Manago, J . Mol. Biol., 1969, 39, 389.

6o

Organophosphorus Chemistry

130

Polynucleotide ligase from E. coli which have been infected with T4bacteriophage will repair single-stranded breaks in double-stranded DNA, and the total synthesis62 of a gene for the principal alanine tRNA in yeast depends on the use of this enzyme to join base-paired oligodeoxyri bonucleotide duplexes with protruding single-stranded ends. The ligase enzyme can also catalyse the joining of DNA duplexes which do not possess protruding single strands, provided the deoxynucleoside at the 5’-end is phosphorylated and the complementary deoxynucleoside opposite to it has a free 3’-hydro~y-group.~~ The enzyme will also catalyse the joining of oligodeoxyribonucleotides on ribonucleotide templates and uice A synthetic, bihelical polydeoxyribonucleotide containing repeating dinucleotide sequences has been prepared with the aid of T4polynucleotide l i g a ~ e . Circular ~~ polynucleotides so obtained have been observed by electron microscopy. As mentioned in last year’s Report, aromatic phosphoramidates have been used to protect 5’-phosphoryl groups in the stepwise synthesis of oligodeoxyri bonucleotides.66 The appropriate monomer units are coupled with DCC and the phosphoramidate protecting group is removed when required with isoamyl nitrite.s7 A rapid and general preparative method for oligonucleotides has been developed 6* based on phosphoramidates of the highly lipophilic 4-aminophenyltriphenylmethane(25). Purification of ROP(O)(OH)NHPh

C H ON0

ROP(O)(OH),

intermediates can be achieved by solvent extraction rather than timeconsuming anion-exchange or gel-filtration methods. The spectroscopic and chromatographic properties of a large number of trinucleoside diphosphates have been published, and a general approach to the synthesis of oli gori bonucleo t i des out lined The amino-acid acceptor ends of a number of tRNAs terminate with H. G. Khorana, Piire Appl. Chem., 1971, 25, 91. V. Sgaramella, J . H . van de Sande, and H . G. Khorana, Proc. Nut. Acad. Sci. U.S.A., 1970, 67, 1468. K. Kleppe, J. H. van de Sande, and H. G. Khorana, Proc. Nut. Acad. Sci. U.S.A., 1970, 67, 68. V. H. Paetkau and H. G . Khorana, Biochentistry, 1971, 10, 1511. E. Ohtsuka, M. Ubasawa, and M. Ikehara, J . Amer. Chem. SOC.,1970, 92, 5507. E. Ohtsuka, K . Murao, M. Ubasawa, and M. Ikehara, J . Amer. Chem. Soc., 1969, 91, 1537. K . L. Agarwal, A . Yarnazaki, and H. G. Khorana, J . Anier. Chem. SOC., 1971, 93, 2754. A. Holjr, Coll. Czech. Chent. Comni., 1970, 35, 3686.

Phosphates and Pliosphotinres of’ Biocheniica f Interest

131

CpCpApCpCpA and this hexanucleotide has been prepared from appropriately protected trinucleotides using a sulphonyl chloride as condensing agent.70 2’(3’)-0-Glycyl esters of Cpl and dCpA have been prepared as potential substrates of ribosomal peptidyl t r a n s f e r a ~ e .While ~~ the glycyl ester of CpI released the polypeptide chain from polylysyl-tRNA in a ribosomal system from E. coli, the dCpA derivative showed little activity. Phosphoramidate analogues of dideoxyribonucleoside phosphates (26) and trideoxyribonucleoside phosphates are acid labile and can be hydrolysed e n ~ y m i c a l l y . ~Snake ~ venom phosphodiesterase cleaves (26) to thymidine and 5’-deoxy-5’-aminothymidine (27; R = H). The latter presumably arises by spontaneous decomposition of the phosphoramidate (27; R = PO,H,) and P - 0 fission must have occurred during the initial hydrolysis. With acid or spleen phosphodiesterase, (26) gave Tp and (27; R = H), i.e. P-N fission occurred.

Hydrolysis of RNA by alkali or pancreatic RNase leads initially to fragments which terminate in 2’,3’-cyclic phosphodiesters. Micrococcal nuclease, on the other hand, gives rise to fragments terminating in 3’-phosphomonoester groups which facilitate their isolation, and this enzymic hydrolysis has been used to prepare 3’-ri bodinu~leotides.~~ The degradation of RNA catalysed by Zn” ions at neutral pH does not occur in a random manner.74 At high zinc concentrations there is preferential cleavage next to cytidine residues but little cleavage next to guanosine. 2’,3’-Cyclic phosphates are intermediates in this degradation and the opening of the cyclic phosphates to the 2’(3’)-phosphates is also catalysed by zinc ions.76 The interconversion of 2’- and 3‘-phosphates, however, does not take place under conditions of the degradation. Liquid 70

71

74 7G

E. Ohtsuka, M. Ubasawa, and M. Ikehara, J . Amer. Chem. SOC.,1971, 93, 2296. J. Zemlicka and S. Chladek, Biochemistry, 1971, 10, 1521. R. L. Letsinger and W. S. Mungall, J. Org. Chem., 1970, 35, 3800. E. Sulkowski, A. M. Odlyzko, and M. Laskowski, Analyt. Biochem., 1970, 38, 393. G . L. Eichhorn, E. Tarien. and J. J. Butzow, Biochemistry, 1971, 10, 2014. J . J . Butzow and G . L. Eichhorn, Biochemistry, 1971, 10, 2019.

132

Organophosphorus Chemistry

hydrogen fluoride will liberate heterocyclic bases from DNA and RNA 7 7 and, moreover, pyrimidine nucleotides which are normally stable to acid are broken down. The conformations of ~-adenylyl-(3’+ 5’)-~-adenosine (28) and ~-adenylyl-(2’-+ 5’)-~-adenosine(29), as deduced from circular dichroic spectra, are different from the corresponding ~ ~ - d i n u c l e o t i d e78s . ~The ~~ ‘H n.m.r. and U.V. absorption spectra of (28) and (29) are the same as the DD-dimers and their chromatographic and electrophoretic properties appear identical. While (28) and (29) are resistant to enzymic hydrolysis they form complexes with polyU. 781

(‘8)

D. Nucleoside Thioph0sphates.-Information on the mechanism of action of enzymes, e.g. pancreatic RNase,’O has been obtained with the aid of nucleoside thiophosphates. Moreover, polyribonucleotides with a phosphorothioate backbone are good inducers of interferon :al hence there has been considerable interest in nucleoside thiophosphates in recent years. The synthesis of nucleoside 5’-phosphorothioates has been described in detail,a2 thiophosphorylation of the nucleoside being achieved with tri-imidazolyl-1-phosphine sulphide (30). Intramolecular cyclization of adenosine 5’-phosphorothioate with an aryl sulphonyl chloride gave the 3’,5’-OO-cyclic phosphorothioate. In this instance, DCC could not be used as desulphurization occurred leading to NN-dicyclohexylthiourea. The cyclic phosphorothioate shows no enzymic activity with either cyclic 3’,5’-nucleotide phosphorodiesterase 83 or phosphorylase b kinase. Thiophosphoryl chloride will also react with protected nucleosides to give 77

D. Lipkin, B. E. Phillips, and J. W. Abrell, J . Org. Chem., 1969, 34, 1539. I. Tazawa, S. Tazawa, L. M. Stempel, and P. 0. P. Ts’o, Biochemistry, 1970, 9, 3499. N. S. Kondo, H. M. Holmes, L. M. Stempel, and P. 0. P. Ts’o, Biochemistry, 1970, 9 ,

70

Y. Kanaoka, K. Itoh, E. Sato, A. Nomura, and Y. Mizuno, Chem. and Pharm. Bull.

81

(Japan), 1970, 18, 1475. D. A. Usher, D. I. Richardson, jun., and F. Eckstein, Nature, 1970, 228, 663. E. De Clercq, F. Eckstein, H. Sternbach, and T. C. Merigan, Virology, 1970, 42,421. F. Eckstein, J. Amer. Chem. SOC.,1970, 92, 4719. F. Eckstein and H. P. Baer, Biochim. Biophys. Acta, 1969, 191, 316.

3419.

8a

Phosphates and Phosphonates of Biochemical Interest

133

5’-pho~phorothioates;~~~ 85 however, the yields of product are lower than with (30). 5’-Deoxy-5’-thioinosine phosphate (3 1) has been prepared by treating 5’-deoxy-5’-iodoinosine (32) with trisodium phosphorothi~ate.~~

KOH + P(S)CI3 + ROP(S)CI,

11J)

ROP(S)(OH),

+ NaI Silver ions will oxidatively desulphurize nucleoside and other phosphorothioates to generate a phosphorylating agent. This reaction has been utilized for the preparation of nucleotide coenzymes 88 and has the advantage that it can be carried out on a large scale without the formation of contaminating symmetrical pyrophosphates.

OAg

HO

OH

E. Physical Methods and Analytical Techniques.-Nucleotide ‘maps’ of enzymic digests of DNA have been obtained 87 using the same ionophoretic techniques as have been developed 88 for RNA digests. Pancreatic DNase and Neurospora crassa endonuclease produce very similar ‘maps’ with E. coli DNA but this technique still awaits the discovery of specific DNases. 84 86

T. Hata and I. Nakagawa, Bull. Chem. SOC.(Japan), 1970, 43, 3619. K. Haga, M. Kainosho, and M . Yoshikawa, Bidl. Chem. SOC.(Japan), 1971, 44, 460. T. Hata and I. Nakagawa, J . Amer. Chern. SOC.,1970, 92, 5516. K . Murray, Biochem. J., 1970, 118, 831. G. G. Brownlee and F. Sanger, EuropeanJ. Biochem., 1969,11, 395; G . G. Brownlee, F. Sanger, and B. G, Barrell, J . Mol. Biol., 1968, 34, 379.

134

Organophosphorus Chemistry

Oligodeoxyribonucleotides of known structure have been linked to insoluble cellulose or agarose supports with the aid of either a watersoluble carbodi-imide 8Q or cyanogen bromide activation.OO Chromatographic columns consisting of cellulose-bound oligonucleotides preferentially retain complementary oligodeoxyribo- and oligori bo-nucleotides, and these can be eluted using a linear temperature gradient.8QIt is claimed that such chromatographic systems are of sufficient resolution to separate oligonucleotides differing by one nucleotide residue. The successful separation of oligonucleotides on hydroxyapatite columns in the presence of 7 M urea has also been re~0rted.O~ A method for the direct spectrophotometric determination of dinucleoside monophosphates has been developed which relies on changes in U.V. absorbance after enzymic h y d r o l y ~ i s . Hydrolytic ~~ fission of the dinucleoside monophosphate with a phosphodiesterase causes a change in the U.V. absorbance of the solution allowing the 5'-nucleoside to be estimated. Addition of a phosphomonoesterase to the hydrolysate causes a further change in U.V. absorbance, allowing the 3-nucleoside to be estimated. 2 Coenzymes and Cofactors

A. Phosphoenolpyruvate. -The mechanisms of hydrolysis of phosphate esters of phosphoenol pyruvic acid (33) have been described in detail,O3 and lHOstudies confirm an earlier postulateg4that attack by water on the cyclic acyl phosphate (34) occurs at phosphorus and not at carbon. I n the enolase reaction, the reversible interconversion of 2-phosphoglyceric acid(35)

(34)

(35)

and PEP (33), abstraction of hydroxide occurs anti to the C-2 proton, e.g. (3R)-phosphoglyceric acid-3-d (36) is converted into PEP-3-d (37).05 Hence, in the reverse reaction the hydroxide comes from below the plane and the proton is added from above the plane of (33). There are two classes of enzymes which interact with PEP, those in which there is a tautomeric C. Astell and M. Smith, J. Biol. Chem., 1971, 246, 1944. M. S. Poonian, A. J. Schlabach, and A. Weissbach, Biochemistry, 1971, 10, 424. K. W. Mundry, Bull. SOC.Chim. biol., 1970, 52, 873. R. A. Felicioli, S. Cervelli, P. L. Ipata, and C. A. Rossi, European J . Biochem., 1970, 17, 533. w

K. J. Schray and S. J. BenkoviC, J. Amer. Chem. SOC.,1971, 93, 2522. V. M. Clark and A. J. Kirby, J. Amer. Chem. SOC.,1963,85, 3705. M.Cohn, J. E. Pearson, E. L. O'Connell, and I. A. Rose,J. Amer. Chem. Soc.. 1970,92, 409 5.

Phosphates and Phosphonates of Biochemical lnterest

135

shift of electrons to C-3 during the reaction, e.g. pyruvate kinase or PEP carboxykinase, and those in which there is a tautomeric shift of electrons in the opposite sense towards C-2, e.g. enolase. Pyruvate kinase interacts strongly with D-phospholactate (38) but only weakly with the L-isomer,

Me, / H C HOOC' 'OPO,H,

presumably because of steric interaction between the methyl group of ~ - ( 3 8 )and the proton-donating group of the enzyme.Q6PEP carboxykinase interacts strongly with ~ - ( 3 8 )and weakly with the D-isomer; an explanation is that the methyl group of ~ - ( 3 8 )can lie in the carbon dioxide binding site of the enzyme. Enolase shows no preference for either enantiomer of (38). B. Nicotinamide and Flavin Coenzymes.-High-frequency (220 M Hz) 'H n.m.r. spectroscopy shows that there are differences in conformation between oxidized and reduced pyridine c o e n ~ y m e s . A ~ ~preliminary report on the 31Pn.m.r. spectra of NAD+ and NADH confirms these observations,QHas the spectrum of NADf consists of an AB quartet while there is only a single resonance discernible in the spectrum of NADH. Catalysis by flavoenzymes has been reviewed gg and various analogues of FAD have been prepared (e.g. P1-adenosine-P3-riboflavintriphosphate * O 0 and flavin-nicotinamide dinucleotide lol) which show little enzymic activity. The kinetic constants of the interaction between nicotinamide-4-methyl-5acetylimidazole dinucleotide (39) and lactic dehydrogenase suggest the presence of an anionic group near the adenine residue at the coenzyme binding site of the enzyme.lo2 u6 n7 gu

loo

lo2

T. Nowak and A. S. Mildvan, J . Biol. Chem., 1970, 245, 6057. R. H. Sarma and N. 0. Kaplan, Biochemis/ry, 1970, 9, 539,557. R. H. Sarrna, Fed. Proc., 1971,30, 1087 Abs. A. H. Neims and L. Hellerman, Ann. Rea. Biochem., 1970, 39, 867, E. D. Khomutova, T. A. Shapiro, and V. M . Berezovskii, Zhur. obshchei Khim., 1970, 40, 470 (Chem. Abs., 1970, 73, 4133). L. M. Mel'nikova and V. M. Berezovskii, Zhur. obshchei Khim., 1970, 40, 918 (Chem. Abs.. 1970, 73, 56 355). C. Woenckhaus, R . Kaleja, and P. Heik, L . Nn//trfursch., 1970, 25b, 1252.

136

Organophosphorirs Chemistry

(39) \+licre R

--

n i c o t i n a m i d c - I -( 3-p-11-t~ b n f u ~ ~ i n o s ~ 1 ) - . 5 ' - ~ l y r I~ ~ ~ ~ I l o s ~ ~ I ~ ~ ~ t

C. Nucleoside Diphosphate Sugars.- A polyprenol phosphate containing eleven isoprene units is involved in the biosynthesis of various bacterial cellwall components.lo3As mentioned in last year's Report, another isoprenoid phosphate, dolichol monophosphate (40), is an intermediate in sugar 0

I1 H-fCH,C( hfC)yCt I C H 2 J ~ C * H , C H hlc)CH,CH,Of'OR ( I

OH

transfer in animal tissues lo4when UDPGlc, UDPGlcNAc, and GDPMan can act as donors with the formation of the respective dolichol monophosphate sugars.1o5 UDPGal and UDPGalNAc do not function as sugar donors with this enzyme system suggesting that there are differences in glucose and galactose metabolism in animals. A particulate, cell-free enzyme of Mycobacterirrm tuberculosis catalyses the incorporation of mannose from GDPMan into several lipids. The major product of this reaction has been identified as the mannose 1-phosphate ester of decaprenol (41).lo6 CH,OH

~ ~ * ~ ~ ~ ~ - * f CI i i ; C H = I : o C H l j ; I I I4 0 € 10

(-I])

In animal tissues the synthesis of UDPGlc from UTP and glucose-1phosphate is catalysed by a pyrophosphorylase of widespread o c c ~ r r e n c e . ' ~ ~ With the enzyme from human liver, there is no specificity for either the 103

104

106

106

107

A. Wright, M. Dankert, P. Fennesey, and P. W. Robbins, Proc. Nat. Acad. Sci. U.S.A., 1967, 57, 1798; Y. Higashi, J. L. Strominger, and C. C. Sweeley, Proc. Nut. Acad. Sci. U.S.A., 1967, 57, 1878; M. Scher, W. J. Lennartz, and C. C. Sweeley, Proc. Nut. Acud. Sci. U.S.A., 1968, 59, 1313. N. H. Behrens and J. F. Leloir, Proc. Nut. Acud. Sci. U.S.A., 1970, 66, 153. N. H. Behrens. A. J. Parodi, L. F. Leloir, andC. R. Krisman, Arch. Biuchem. Biophys., 1971, 143, 375'. K. Takayama and D. S . Goldman, J . Biof. Chem., 1970, 245, 6251. S. Levine, T. A. Gillett, E. Hageman, and R. G. Hansen, J. Biof. Chem., 1961, 244, 5729.

Phosphates and Phosphonates of Biochemical Interest

137

nucleoside or the hexose components of the coenzyme.lo8 The activity ratios of UDPGlc and UDPGal remained constant throughout the isolation of the enzyme and, hence, the human liver does not appear to contain a separate UDPGal pyrophosphorylase.

D. Coenzyme A.-Succinyl phosphate (42) lo9 reacts rapidly and nonenzymatically with CoA in the pH range 3-8 to yield succinyl CoA (43).llo This reaction is dependent on the presence of a suitably situated free carboxy-group as such nucleophilic attack at carbon is not known with other acyl phosphates.lll Moreover, maleyl phosphate reacts rapidly with CoA while fumaryl phosphate fails to react under the same conditions. Hence the formation of a cyclic intermediate (44) from succinyl phosphate is 0 I1 COPO, € 1,

-0 OPO,H,

--Q P

-:COOH

(42)

P

CoA'S'fI

++CoASCOCH,C€I,C'OOI 1 (43)

+

~r,ro.,

(44) probable. From kinetic evidence it is thought that succinic anhydride is not a likely intermediate in this reaction. Analogues of CoA with modified pantetheine residues have been synthesised by the phosphoromorpholidate method,l12 but no mention is made of their biological activity. 3 Naturally Occurring Phosphonic Acids A. Aminophosphonic Acids.-The Michael addition of a dialkyl phosphite to acrylonitrile leads to C-P bond formation and the production in high yield of derivatives of 2-aminoethylphosphonic acid (45).l13 This synthetic method appears to be preferable to those already described.'14 The chemical shift of phosphorus in phosphonates occurs in a region removed from the shift in phosphates115 and 31Pn,m.r. has been used to detect phosphonates in lipids.'lR Phosphonates have also been detected by l H n.m.r. spectroscopy as P-CH, protons appear at higher field than P-0- CH2 lo8 lo* 110 112

l1:I

'I4 115

J. K. Knop and R. G . Hansen, J . Biol. Chetn., 1970, 245, 2499. J. G. Hildebrand and L. B. Spector, J . Biol. Chem., 1969, 244, 2606. C. T. Walsh,jun., J . G. Hildebrand, and L. B. Spector,J. B i d . Chem., 1970, 245, 5699. G. DiSabato and W. P. Sencks, J . Atner, Chetn. SOC.,1961, 83, 4393. M. Shimizu, 0. Nagase, Y . Hosokawa, H . Tagawa, and Y . Yotsui, Chetn. arid Phurtn. Bull. (Japan), 1970, 18, 838. J . Barycki, P. Mastalerz, and M. Soroka, Tetrahedrott Letters, 1970, 3147. L. D. Quin, Topirs in Phosphnriis Chertiisrry, 1967, 4, 23. V. Mark, C . H. Dungan, M. M . Crutchfield, and J . R . Van Warer, Topics i/i Pliosphorris Chetnistr.v, 1967, 5, 227. T. Glonek,T.O. Hcnderson. R . L. Hilderbrand,andT. C. Myers,Scienc.e,1970. 169, 192. C. Benezra, S. K. Pavanaram, and E. Baer, Cmtrd. J . Biocheni., 1970, 48, 99 I .

138

Organophosphorus Chemistry

A glyceryl 2-aminoethylphosphonolipid has been isolated from Tetrahymenapyr~ormis11* and (45) has been detected by g.1.c.-mass spectrometry in both the lipid and proteinaceous fractions of human brain."@ The zwitterionic (45) was converted into volatile (46) by acetylation and met hy I a t ion. Phosp honol i pids derived from N-met hyl-(45) have been synthesised by acetylation of N-methyL(45) and subsequent conversion to the phosphorochloridate for the phosphorylation step.lZ0

Bacillus cerciis degrades (45) to acetaldehyde with fission of the C--P lZ2 An enzyme which catalyses the decomposition of phosphonoacetaldehyde (47),123an intermediate in this degradation to acetaldehyde, has been characterized.lZ2 The enzyme will only degrade (47) and will not breakdown a number of other phosphonates, including phosphonomycin (48).lZ4 "'r'llvatc

;I I;]ti; ric

0. Phosphonomycin.-Since the publication of the synthesis of (48),126 which was described in last year's Report, numerous patents have been filed of syntheses of this antibiotic.lZs The isomerization of the transiin 118 120 121

122

123

iza

126

120

H. Bcrger and D. J. Hanahan, Biochim. Biuphys. Acra, 1971, 231, 584. J . A. Alhadeff and G . D. Daves, jun., Biochemistry, 1970, 9, 4866. E. Baer and S . K. Pavanaram, Canad. J. Biuchem., 1970, 48, 979, 988. J. M. La Nauze and H. Rosenberg, Biochim. Biophys. A d a , 1968, 165, 438. J. M. La Nauze, H. Rosenberg, and D. C. Shaw, Biochim. Biophys. Acra, 1970, 212, 332. A. F. Isbell, L. F. Englert, and H. Rosenberg, J. Org. Chem., 1969, 34, 755. D. Hendlin, E. 0.Stapley, M. Jackson, H. Wallick, A. K. Miller, F. J. Wolf, T. W. Miller, L. Chaiet, F. M. Kahan, E. L. Foltz, H. B. Woodruff, J. M. Mata, S. Hernandez, and S. Mochales, Science, 1969, 166, 122. B. G. Christensen, W. J. Leanza, T. R. Beattie, A. A. Patchett, B. H. Arison, R. E. Ormond, F. A . Kueld, jun., G. Albers-Schonberg, and 0. Jardetsky, Science, 1969, 166, 123. B. G. Christcnsen and R. A. Firestone, G.P., I 924 135 (Chent. Abs., 1970,72,43 870); J. M.Chemerdaand E. J. Glamkowski, G.P., 1 924 173 (Chem. A h . , 1970,72,43 871); R. A. Firestone, G.P., 1924098 (Chem. Abs., 1970, 72, 90629); P. I. Pollak, B. G. Christensen, and N. L. Wendler, G.P.. 1924 169 (Chem. Abs., 1970, 72, 100882); R. A. Firestone, G.P., 1 924 138 (Chem. Abs., 1970, 72, 111 613); R. A. Firestone and E. J . Clamkowsky, G.P., 1924 105 (Chem. Abs., 1970, 72, 132 952); J. M. Chernerda and E. J. Glamkowsky, G.P., 1 924 118 (Chem. Abs., 1970, 72, 132 953).

Phosphates and Phosphonates of Biochemical Interest

139

isomer of (48) by U.V. irradiation has been reported.127 It is interesting to note that 2-halogenoethylphosphonates(49) are biologically active and function as plant growth stimulators.12B

4 Oxidative Phosphorylation I n a chemical model for mitrochondrial oxidative p h o s p h ~ r y l a t i o n ,it~ ~ has been proposed that the mitochondria1 membrane, to which ATP and

inorganic phosphate are attached, is held in an extended inactive form (50) by coulombic repulsion of positive charges. On reduction of the membrane by NADH one positive centre is removed, and folding of the membrane can occur with extrusion of water. This creates a non-aqueous environment around the ADP (51) and a metal ion can now catalyse the formation

n

+ ATI' of ATP. The latter is released by a membrane-bound ATPase. Oxidation of the membrane by the next component in the electron transport chain regenerates a positive charge and the membrane reassumes the extended inactive form. A dynamic model has been proposed for the synthesis of ATP during oxidative phosphorylation in which ADP and inorganic phosphate combine directly to give a quinquecovalent intermediate.12QWhile such a model may be valuable in drawing attention to the possible participation of quinquecovalent intermediates in ATP synthesis, no mention is made of the role of oxidation in this reaction. The synthesis of ADP and ATP by the aerial oxidation of ferro-haeniochrome solutions is known 13') and the participation of an imidazole lz7 13@

lz9

E. E. Harris, U.S.P. 3 496 080 (Chr*rir.Ahs.. 1070, 72,90 633). D. E. Randall, Fr. P. 1 569 694 (Chem. A h . , 1970, 73. 35 507). E. F. Korman and J. McLick. Proc. Nor. Acad. Sci. U.S.A., 1970, 67, 1130. W . S. Brinigar, D. €3. Knaff, and J . ii. Wang, Biochenristr.v, 1967, 6. 36; 1'.A . C'oopcr, W. S. Brinigar, and J . El. Wang. J . Biol. Chcnr., 1968, 243. 5854

140

Organophosphorus Chemistry

phosphate (52) in this reaction has been suggested.131 The formation of (52) when visible light is absorbed by haematoporphyrin solutions in phosphate buffers containing imidazole has been An anion-radical e.g. (53), may be an intermediate, and oxidation of (53) followed by expulsion of water could lead to (52). E.s.r. studies on the frozen reaction medium show the presence of free radicals which may be related to (53).

During the auto-oxidation of 1,4-dihydronicotinamides catalysed by NNN’N’-tetramethyl-4-phenylenediamine (TM PD), 5,6-nicotinamide hydrates can be The auto-oxidation of pyridine solutions of 1-n-propyl-6-hydroxy-1,4,5,6-tetrahydronicotinamide(54; R = OH) is also catalysed by TMPD provided that phosphate or arsenate is Pyrophosphate and pyridinium ions are produced and a phosphorylating species must be generated. It is suggested that (54; R = OPO,H,) is an intermediate which is oxidized to (55). Phosphoryl transfer from (55) involves P-0 bond cleavage giving rise to (56). Formation of pyridinium ions from (55) requires C-0 cleavage and so both P-0 and C-0 cleavage must occur during this oxidative reaction. Hydroquinone phosphates (57)transfer phosphate to substrates following

WMe ‘ ’ Me

OH

(57) 131

lsa lS3

13’

J . H. Wang, Accounts Chem. Res., 1970,3, 90. S.-I. Tu and J. H. Wang, Biochemistry, 1970,9, 4505. E. J. H. Bechara and G. Cilento, Biochemistry, 1971, 10, 1831. E. J. H. Bechara and G. Cilento, Biochemistry, 1971, 10, 1837.

Phosphates and Phosphonates of Biochentical Interest

141

chemical oxidation 136 and they are also oxidized by mitochondria with release of inorganic p h 0 ~ p h a t e . lWhile ~ ~ the phosphate release is dependent on oxygen uptake by the mitochondria, addition of ADP does not stimulate the oxidation of (57). It seems unlikely, therefore, that ADP is a specific phosphoryl acceptor in this reaction. 5 Sugar Phosphates and Phosphonates

A. Pentoses.-L-Ascorbic acid 2- and 3-phosphates, together with their phosphate esters, give a characteristic colour with ferric chloride 13' and this colour reaction has been used in a study of the hydrolysis of L-ascorbic acid 3-phosphate (58). The acid-catalysed, pseudo-first-order hydrolysis proceeds with P-0 bond as does the bromine oxidation of its phenyl Both of these observations can be rationalized if ( 5 8 ) is

1t o

\

0PO:,H 2

t 58) regarded as a P-XYZ system 135a which undergoes electron withdrawal from the C=C bond by either protonation or attack by a bromonium ion. The molar ratio of methyl phosphate to orthophosphate formed during the solvolysis of the monoanion of ( 5 8 ) in methanol-water mixtures is close to the molar ratio of the solvents, indicating the presence of a nonspecific phosphorylating agent.138 During the hydrolysis of the dianion, however, relatively little methyl phosphate is produced but condensed phosphates can be detected in the reaction products. Isomers of D-apiofuranosyl 1-phosphate have been prepared by treating a mixture of fl-D-apio-D-furanosyl and fl-D-apio-L-furanosyl tetra-acetates with crystalline phosphoric acid.140 a-D-ApiO-D- (59) and a-D-apio-Lfuranosyl- 1-phosphate (60) and their cyclic phosphates were separated by chromatography and identified by lH n.m.r. D-Apiose is metabolized in parsley and Lemna minor 141 with the possible formation of UDP-D-apiose. L . minor will convert UDP-a-glucuronic acid into a-D-apio-D-furanosyl1,2-cyclic phosphate (61) but no evidence of UDP-D-apiose was found,140 although it is possible that (61) arose from the rapid hydrolysis of UDP-Dapiose. 1360

136

137

138

158

l(o 141

V. M. Clark and D. W. Hutchinson, Progr. Org. Chem., 1968, 7 , 75; Ir V. M. Clark, D. W. Hutchinson, G. W. Kirby, and A. R. Todd, J. Chem. Soc., 1961, 715. J. M. Young, Biochem. J . , 1970, 118, 719. H. Nomura and S. Morimoto, Chem. and Pharm. Bull. (Japan), 1971, 19, 335. H . Nomura, M. Kuwayarna, T. Ishiguro, and S. Morirnoto, Chem. and Pharm. Bull. (Japan), 1971, 19, 341. V. M. Clark, J. W. B. Hershey, and D. W. Hutchinson, Experienfia, 1966, 22, 425. J. Mendicino and R . Hanna, J. Biol. Chem., 1970, 245, 6113. J. M. Picken and J. Mendicino, J . Biol. Chent., 1967, 242, 1629.

142

Orgnnnphosphorus Chemistry

Crystalline phosphoric acid has also been used to prepare sugar diphosphates, e.g. a-D-ribose 1,5-diphosphate (62) and hexose 1 , 6 - d i p h o ~ p h a t e s . ~ ~ ~ In this reaction the fully acetylated sugar 5- or 6-phosphates were phosphorylated and the protecting groups removed by alkali. Only a-Iphosphates were isolated and no evidence of the /?-anomers could be detected.

HO

OH

(59)

Hd

OH

B. Hexoses.-Muramic acid 6-phosphate (63), which occurs in the cell walls of bacteria,143has now been ~ y n t h e s i s e d thus , ~ ~ ~confirming the structure of this acid-stable compound.

(r> CFJ,OPO,I I,

\ltb(,t 7 )t )I I

OH

1 IC.,

N H, (63)

Tetra-0-acetyl-a-D-glucopyranosylbromide (64) does not undergo the Michaelis-Arbusov reaction with trialkyl phosphites, instead 2-acetoxy3,4,6-tri-0-acetyl-~-glucal (65) is formed in high yield. The tetra-0-methyl phosphonates (68) have been ether gives a similar p r 0 d ~ c t . l ~Sugar ~ prepared from (64) using mercuribromide derivatives of dialkyl phosphites (66). Presumably the cation (67) is an intermediate in this reaction. The addition of phosphites to keto sugars is another reaction which has been Ira

146

R. Hanna and J. Mendicino, J . Biol. Chem., 1970, 245, 4031. Y . Araki, T. Nakatani, R. Makinio, H. Hayashi, and E. Ito, Biochem. Biophys. Res. Comm., 1971, 42, 684. Y . Konami, T. Osawa, and R. W. Jeanloz, Biochemistry, 1971, 10, 192. H . Paulsen, J. Thiem, and M. Moner, Tetrahedron Letters, 1971, 2105.

Phosphates and Phosphonates of Biochemical Interest

143

used to prepare sugar p h o s p h o n a t e ~14’ , ~ ~and ~ ~ lithium diphenylphosphide reacts with epoxides or sulphonate esters of carbohydrates, e.g. (69), with A mixed anhydride of carbamic and the formation of C-P phosphorous acids (70) reacts with alcohols and sugars to give the corresponding phosphite CH,OAc

AcO

€1-

14* 14’ 148

‘0

I

I H

H. Paulsen, W. Greve, and H. Kuhne, Tetrahedron Lerters, 1971, 2109. Y. A. Zhdanov and L. A. Uzlova, Zhur. obshchei Khim., 1970, 40, 2138 (Chem. Abs., 1971, 74, 42 579). L. D. Hall and P. R. Steiner, Chem. Comm., 1971, 84. N. K. Kochetkov, E. E. Nifant’ev, I. P. Gudkova, and M. P. Koroteev, Zhur. obshchei Khirn., 1970, 40,2199 (Chern. Abs., 1971, 74, 112 328).

144

Organophosphorus Chemistry

6 Inositol Phosphates and Phospholipids A. Inositol Phosphates.-Phosphatidyl inositol (71) is hydrolysed in mammalian tissues to myo-inositol 1,2-cyclic phosphate (72).150 myoInositol 1-phosphate (73) is released simultaneously but is not converted into (72) by the enzyme system. Periodate oxidation of (73) liberates orthophosphate quantitatively, the unstable dialdehyde phosphate (74) being an intermediate.151 Little or no orthophosphate is released from glucose 6-phosphate under the same oxidative conditions, and this reaction has been used to assay (73). 0H

B. Phospholipids.--Phosphorylation of monoacyl propane-l,3-diols with 2-bromoethyl or 5-bromopentyl phosphorodichloridate (75; n = 2 or 5 ) followed by treatment of the product with triethylamine leads to deoxylecifhins,lS2 and other lecithin analogues have been synthesised in a similar manner.163 Five of the six possible isomers of rnonoacyl glycerol-3phosphoryl choline are known;154 the synthesis of the sixth isomer using (75) has been This isomer is, however, biologically inactive. The phosphatidyl glucose, p-D-glucopyranosyl-( I -myristoyl-2-oleoyl-synglycero-3-phosphate) (76), can be prepared by coupling acetobromoglucose (64) with the silver salt of the corresponding benzyl phosphatidic The acetyl groups can be preferentially removed from the glucose moiety by the action of buffer at pH 9.7. The chemical and chromatographic R. M. C . Dawson, N. Freinkel, F. B. Jungalwala, and N. Clarke, Biochem. J., 1971, 122, 605. 151 J. E. G . Barnett, R. E. Brice, and D. L. Corina, Biochem. J., 1970, 119, 183. l a a H. Eibl and 0. Westphal, Annulen, 1970, 738, 170. lh3 H. Eibl and 0. Westphal, Annulen, 1970, 738, 174. lK4 G. H. De Haas and L. L. M. Van Deenen, Biochim. Biophys. Actu, 1965, 106, 315. lsS H. Eibl and 0. Westphal, Annulen, 1970, 738, 161. 166 H. M. Verheij, P. F. Smith, P. P. M. Bonsen, and L. L. M. Van Deenen, Biochim. Biophys. Actu, 1970, 218, 97.

160

Phosphates and Phosphoriotes of Biocheniicul Interest

CH20"

145

R'COOCH, I

110

I10 ( 7 6 )where RCO

==

0

myristoyl aiid K ' C O

-

olcovl

properties of (76) are different from those of a glucose-containing phospholipid isolated from Mycoplasmu l a i d l n ~ ~ i iThreonine .~~~ phosphoglycerides have been prepared by coupling a protected glycerol-3-phosphatidic acid (77) with the t-butyl ester of N-t-butyloxycarbonyl-L-threonine(78) using an aryl sulphonyl chloride as condensing agent,15*and phosphatidic acids derived from dihydroxypropylphosphonic acid (79) have been descri bed.160

7 Enzymology Glutamine synthetase from E. coli is regulated in part by the covalent binding of AMP to the enzyme when the specific activity is altered.lB0 Digestion of the adenyl enzyme with trypsin liberates a henecosapeptide containing covalently-bound AMP.lsl This peptide has been sequenced and the AMP is bound to tyrosine (80) confirming an earlier postulate.le2 Edman degradation of a phosphoglycopeptide which had been isolated from a pronase digest of phosvitin, shows that the peptide contains eight successive phosphoserine residues (81).le3 lS7 16* log 1e0

lel

la2 16s

P. F. Smith and C. V. Henrikson, J . Lipid. Res., 1965, 6, 106; N. Shaw, P. F. Smith, and W. L. Koostra, Biochem. J., 1968, 107, 329. J. W. Moore and M. Szelke, Tetrahedron Letters, 1970, 4423. E. Baer and H. Basu, Cunad. J . Biochern., 1970, 48, 1010. D. Mecke, K. Wulff, K. Liess, and H. Holzer, Biochem. Biophys. Res. Comm.,1966, 24, 452. R. L. Heinrikson and H. S. Kingdon, J . Biol. Chem., 1971, 246, 1099. B. M. Shapiro and E. R. Stadtman, J . Biol. Chem., 1968, 243, 3769. R. Shainkin, Fed. Proc., 1971, 30, 1223 Abs.

146

Chemistry

Dihydroxyacetone phosphate (82) is a substrate for a-glycero-phosphate dehydrogenase, aldolase, and triose phosphate i ~ o m e r a s e , and ~ ~ ~ its O-alkyl ethers are intermediates in the biosynthesis of phospholipid^.^^^ In neutral aqueous solution at 20 "C, dihydroxyacetone phosphate exists as an equilibrium mixture of the keto (82), gem-diol (83), and enol (84) forms, as shown by 'H n.m.r. spectroscopy. The proportion of (82) to (83) HOC€12COCH,0P0,tl 2

t 10CH2CCH,0P0,~~,

AOH

HO

(82)

HOCH= C H0 H C H, 0 PO,H, (84)

is temperature dependent and at high temperatures (82) is the major component. This is the primary reactive species with the three enzymes, and it may be relevant that fructose phosphate also reacts enzymically in the keto form.166 1-Fluoro- 1-deoxy-~~-glycerol-3-phosphate ( 8 5 ) is a substrate for glycerol-3-phosphate dehydrogenase but the 1-bromo and 1-chloro analogues are not.le7 The halogeno derivatives were prepared by treating the corresponding epihalogenohydrins with a phosphoric acid and the structure of ( 8 5 ) was elucidated by lH n.m.r. l-O-Alkyl ethers of (82) have been prepared by a route in which the key step was the oxidation of the 2-hydroxy-group of a 1-0-alkyl-3-O-acyl glycerol with DCC-DMS0.1s8 Removal of the acyl group and subsequent phosphorylation gave 1-O-alkyl- (82). 1I p o ' FCH,CHO H CH,OPO, H +--

(85) lo' lab

lo7

len

FCH,CH-CH,

\0/

S. J. Reynolds, D. W. Yates, and C. I. Pogson, Biochem. J., 1971, 122, 285. F. Snyder, M . L. Blank, and B. Malone, J . Biol. Chem., 1970,245,4016; R . L. Wykle and F. Snyder, J . Biol. Chem., 1970, 245, 3047. G. R. Gray and R. Barker, Biochemistry, 1970, 9, 2454. T. P. Fondy, G. S. Ghangas, and M. J. Reza, Biochemistry, 1970, 9, 3272. C. Piantadosi, K . S. Ishaq, R. L. Wykle, and F. Snyder, Biochemistry, 1971, 10, 1417.

Phosphates and Phosphoriates of Biochemical Interest

147

8 Other Compounds of Biochemical Interest Metal ions have a profound influence on the hydrolysis of acetyl phosphate.lee>170 Thus, in the magnesium(i1)-catalysed system P - 0 bond fission is the predominant reaction, while C - 0 bond fission is the major process in the calcium(r1)-catalysed rea~ti0n.l~'It may be that the nature of the acetyl phosphate-metal ion complex has an important bearing on this reaction, and an intermediate such as (86) would favour C - 0 cleavage while (87) might be expected to favour P - 0 cleavage in a bimolecular ~ e a c t i 0 n . l ~ ~ 4-

(86)

(87)

Acetate kinase is phosphorylated by acetyl phosphate and it has been shown that the phosphoenzyme can synthesise ATP from ADP, and acetyl phosphate from The mode of decomposition of carbamyl phosphate in aqueous solution is pH dependent and can proceed with either the production of ammonia and carbon dioxide (equation l), or cyanate (equation 2).'74 No cyanate could be detected during the hydrolysis Nl12C0,P0,H2 NCO-

+ HI'O,= + Ii,O

(2)

of carbamyl phosphate by acyl phosphatase, suggesting that the hydrolysis proceeds as in equation 1, unless an unusually rapid decomposition of cyanate occurs in this ~eacti0n.l'~ Interest in 'presqualene pyropho~phate'l~~ continues and it is claimed 177 that the structure (88) assigned178 to a squalene precursor is incorrect. Presqualene pyrophosphate has been shown to contain a cyclopropyl ring ~~~ (89),177and both (89) and its parent alcohol have been s y n t h e ~ i s e d . 'le0 Mechanisms for the conversion of (89) into squalene have been published.181pla2 C. H. Ostreich and M . M. Jones, Biochemistry, 1966, 5 , 2926. P. J. Briggs, D. P. N. Satchell, and G. F. White, J. Chem. SOC.( B ) , 1970, 1008. 171 J. P. Klinman and D. Samuel, Biochemistry, 1971, 10, 2126. 172 F. J. Farrell, W. A. Kjellstrom, and T. G. Spiro, Science, 1969, 164, 320. l i Y R. S. Anthony and L. B. Spector, J. Biol. Chem., 1970, 245, 6739. 17' C. M. Allen, jun., and M. E. Jones, Biochemistry, 1964, 3, 1238. 176 D. Diederich, G. Ramponi, and S . Grisolia, F.E.B.S. Letters, 1971, 15, 30. 176 H. C. Rilling, J. Biol. Chem., 1966, 241, 3233. W. W. Epstein and H. C. Rilling, J. Biol. Chem., 1970, 245, 4597. 17* G. Popjik, J. Edmond, K. Clifford, and V. Williams, J. Biol. Chem., 1969, 244, 1897. 17B L. J. AItman, R. C. Kowerski, and H. C. Rilling, J. Amer. Chem. SOC., 1971, 93, 1782. l n 0 R. M. Coates and W. H. Robinson, J. Amer. Chem. SOC., 1971, 93, 1785. 181 H. C. Rilling, C. D. Poulter, W. W. Epstein, and B. Larsen, J. Amer. Chem. SOC., 1971.93, 1783. l R 2 E. E. van Tamelen and M. A. Schwartz. J. Amer. Chem. Soc., 1971, 93, 1780. lB0 lio

148

Organophosphorus Chemistry

RC H, C ( h.1 e 1=C I I C H,C H, C H-

/

0

04p’\ H0

c-C H I< \

o /

H y T i O p Z O G I 1,

0

‘r)-oij \\ 0

(88) where K gcranyl

c Mc, // c Mc / 14

Cf1,R

CH,R

‘

(89)

The substrate specificity of farnesyl pyrophosphate synthetase has been studied using 3-methyl-2-alkenyl pyrophosphates (90) as m0de1s.l~~When (90) bears a large side-chain (i.e. R = CIHg),the reaction with isopentenyl pyrophosphate ceases after the formation of (91) and this reaction has been

(90)

(91)

used to synthesise 16,16’-bisnorgeranylgeranyl pyrophosphate.ls4 The acid-catalysed hydrolyses of isopentenyl phosphate and pyrophosphate proceed with P-0 bond fission; on the other hand, hydrolysis of the allylic dimethyl ally1 pyrophosphate occurs with C-0 Neopterin cyclic phosphate (92) has been isolated as an intermediate in the biosynthesis of pteridines from GTP in Comamonas.186 Tracer studies show that the phosphoryl group in (92) originates from the

(92)

a-phosphorus atom in GTP. Neopterin triphosphate which is synthesised from GTP in E. coli does not appear to be an intermediate in Comamonas. Clindamycin (93; R = H), an antibiotic obtained by chlorinating lincomycin, is converted by a species of Streptomyces into inactive phosphoruscontaining These have been shown to be nucleoside 5’-phosphates derived from adenosine, cytidine, guanosine, and uridine. K. Ogura, T. Nishino, T. Koyama, and S. Seto, J . Amer. Chem. SOC.,1970, 92, 6036. T. Nishino, K. Ogura, and S. Seto, J . Amer. Chem. SOC.,1971, 93, 794. B. K. Tidd, J . Chem. SOC.(B), 1971, 1168. 18a J. Cone and G. Guroff, J . Biol. Chem., 1971, 246, 979. lB7 A. D. Argoudelis and J . H . Coats, J . Amer. Chem. SOC.,1971, 93, 534.

lB3

lB4

Phosphates and Phosphonates of Biochemical Interest

149

OH (93)

where R

==

ribonucleosidc 5'-phosphoryl or 14

A new, heat-stable, coenzyme concerned with methyl group transfer has been isolated from Methunobacterium.188 The coenzyme, which is involved in transmethylation reactions prior to methane formation by the organism, contains phosphorus and has a U.V. absorption at 260 nm, suggesting that it may be a nucleotide. The presence of inorganic polyphosphate in electron-dense particulate structures of M. Iuteus has been demonstrated by 31Pn.m.r.,le9 confirming an earlier observation based on chemical 180

B. C. McBride and R. S. Wolfe, Biochemistry, 1971, 10, 2317. T. Glonek, M. Lunde, M. Mudgett, and T. C. Myers, Arch. Biochem. Biophys., 1971,

loo

I. Friedberg and G. Avigad, J . Bacteriol., 1968, 96, 544.

18a

142, 508.

6

8 Ylides and Related Compounds BY S. TRIPPETT

1 Methylenephosphoranes A. Preparation.--The first reverse Wittig olefin synthesis has been rep0rted.l Triphenylphosphine oxide and dicyanoacetylene at 160 "C gave the stable ylide (1 ; 78%); the reaction was reversed at 300 "C. No comparable reaction was observed with a variety of other activated acetylenes but triphenylarsine oxide gave the corresponding stable arsoranes with dicyanoacetylene ( - 70 "C), methyl propiolate, hexafluorobut-2-yne, dimethyl acetylene dicarboxylate, and ethyl phenylpropiolate (1 30 "C). Ph3P0

+ NC*CIC*CN

300 "C p

Ph3P:C(CN)*CO*CN

160 'C:

(1)

Phosphonium fluorides have been used in olefin synthesis without additional base, the fluoride anion being sufficiently strong a base to remove the a-proton from the salts (2; R = Ar or COR') in acetonitrile. Ph,P+*CH,R F-

f- Ph3P:C H R p-N02'C6I14*C3

(2)

p-NO,*C,H,*CH:CHR (31-86%)

Salt-free ylides have been prepared from phosphonium chlorides and bromides by treatment with sodamide in refluxing THF. The sodium halide precipitates and is removed by filtration, Allylidene- and benzylidenetrimethylphosphoranes have been obtained as low melting distillable solids from the phosphonium chlorides and butyl-lithium in ether. The allylidenephosphorane on standing at room temperature slowly decomposed to give methylenetrimethylphosphorane. Previous difficulties in the generation of the ylide from the spiro-phosphonium salt (3) have been overcome by treating the salt with sodium hydride in DMSO in the presence of a carbonyl compound or by refluxing 1 2

s 4

a

E. Ciganek, J . Org. Chem., 1970, 35, 1725. G . P. Schiemenz, J. Becker, and J . Stockigt, Chem. Ber., 1970, 103, 2077. R. Koster, D. SimiC, and M. A. Grassberger, Annalen, 1970, 739, 211. W. Malisch, D. Rankin, and H. Schmidbauer, Cheni. Ber., 1971, 104, 145. N. Ya. Derkach and A. V. Kirsanov, J . Gen. Chern. (U.S.S.R.), 1970, 40, 1411.

YIides arid Related Compoirrids

151

a solution of the salt in t-butanol with benzaldehyde and potassium t-butoxide.8 The resulting unsaturated phosphine oxides were obtained in 18-23% yield.

(3)

( 1 8-2373

The formation of the azo-ylides ( 5 ) from the chlorohydrazones (4) as shown may have involved addition of triphenylphosphine to intermediate 1,3-dipoles or directly to the chlorohydra~ones.~ PhsP

+ RCCl:N*NHPh + Et3N

r:'.,:

+

Ph,P: CR*N:NPh

(4)

(5)

R = COMe, CO,Et, or p-NO,*C,H,

Alkylation of the metallated bis(triphenylphosphiny1)methane (6) with benzyl or methyl chlorides occurred on phosphorus to give the ylides (7). That from benzyl chloride reacted with chlorodiphenylphosphine to give the stable ylide (8).

The dangers of using alkyl-lithiums to generate highly reactive ylides are illustrated by the use of butyl-lithium to prepare the chloromethylene ylide (9). When the resulting solution was treated with the aldehyde (10) the olefins (1 1) and (12) were obtained, in addition to the expected olefin. Presumably the ylides leading to (1 1) and (12) were formed via the quinquecovalent phosphorane (13); migration of a group from phosphorus to the methylene with expulsion of chloride ion would give the salts corresponding to these ylides. For the formation of ylides from triphenylphosphine with dimethyl acetylene dicarboxylate and with halonitroalkenes see Chapter I , Section 2. B. D. Cuddy, J. C. F. Murray, and B. J. Walker, Tetrahedron Letters, 1971, 2397. V. V. Kosovtsev, V. N. Chistokletov, and A. A. Petrov, J . Gen. Chem. (W.S.S.R.), 1970.40, 21 16.

K. Isslieb and H. P. Abicht, J . prakt. Chem., 1970, 312, 456. G . W. Pilling and F. Sondheimer, J . Amer. Chern. SOC.,1971, 93, 1970.

a'",

Organophosphorus Chemistry

152

CTH

Ph,P. + CH,CI BuLi THF, - 70 C

CHO

>

a

C

X

+

H

CH:CHCI

CH:CH Ph

,

Ph P :C HC 1 (9)

+ BuPh,kH,Ph

(I3)

CI-

B. Reactions.-(i) Halides. Whereas ylides are alkylated in the normal way on treatment with a-bromo- or a-iodo-esters, quite different reactions occur with a-fluoro- and a-chloro-acetates. When salt-free ylides were refluxed in benzene with ethyl fluoroacetate or trifluoroacetate l o normal Wittig olefin synthesis took place with the carbonyls of the ester groups to give vinyl ethers, e.g. (14). On the other hand, methyl chloroacetate with Ph3P:CHPh

+ CF3*COzEt

-

PhCH:C(OEt)CF, (14) (78%)

+ Ph,PO

ylides gave l1 only the cyclopropane (1 5 ) , presumably via the anion (16). This anion was partly trapped as the cyclopropane (17) by carrying out the reaction in the presence of an excess of methyl crotonate. Ph:,P:CHR

+ CICH,CO,Me

+ Ph,{;.CH,K

+ CICHC0,Mc (16)

CICH,CO,Me

+ (16) -+

MeO,C*CHCI-CH,-CO,Mc Ph,,P: CHR

C0,Mc ( 1 6 ) hle02C~ c-- h.lcO,C.CH:CH.CO,Mc C0,Mc (15) M e CO,Me

C0,Me

(17) lo

l1

H. J. Bestmann, H. Dornauer, and K. Rostock, Chem. Ber., 1970, 103, 2011. H. J. Bestmann, H. Dornauer, and K. Rostock, Annalen, 1970, 735, 52.

Ylides and Related Compounds

I53

The 1,Sdiene (1 9) was obtained l2 from the salt (1 8) by alkylation of the ylide with ally1 bromide and reduction of the resulting salt with lithium in ethylamine.

The reaction of ylides with phosphorus(1rr) halides has been extended l 3 to the ylides (Me,N),Me,-,P:CH,, n = 1, 2 , or 3. Alkylation of the resulting stabilized ylides (20) with methyl iodide took place on the tervalent phosphorus, e.g. (Me,N),P: CH,

+ Et,PCl

----+

(Me,N),P: CH-PEt, (20) McI

(Me2N)3P:CHOP+-MeEt,I -

Full accounts have appeared of the exchange of trimethylsilyl for chlorosilyl groups on treatment of trimethylsilylylides with chlorosilanes l4 and of the stabilizing effects of the simple silyl (SiH,) group on ~ 1 i d e s . I ~ The exchange process involves nucleophilic attack of the ylide on the silicon of the chlorosilane, e.g.

Me,,P:C(SiMc,),

+ Me,SiCI,

{

SiMe,

I -+Mc,P-C-SiMegI 13

fSiMe3

-C1

J-

,SiMe, hle,P:C, SiMc,CI

+ Me3SiC1 l2 I:’

K . E. Harding and K. A. Parker, Tetrahedron Lerrers, 1971, 1633; see E. H. Axelrod, G. M. Molne, and E. E. van Tamelen, J . Amer. Chem. Soc., 1970, 92, 2139. K. Isslieb and M. Lischewski, J . prclkr. Chem., 1970, 312, 135. H. Schmidbauer and W. Malisch, Chem. Ber., 1971, 104, 150. H. Schmidbauer and W. Malisch, Chern. Ber., 1970, 103, 3007.

154

0rgnnophosphorids Chemistry

Silyl migrations readily occur in silylated ylides to give the ylides of optimum stability.16 Thus, deprotonation of the salts (21) and (23) gave the ylides (22) and (24), respectively. Intermolecular silyl transfers, from one ylide (or the corresponding phosphonium salt) to another, also lead to maximum stabilization. Silyl transfer does not occur l7 in the product (26) from methylenetrimethylphosphorane and the chlorodisilane (25), pre-

Sihlc:,

(32)

(21 1 hl c t

I

hlc31’--C‘ t 4

-

--

tI

- f

I Sihlc,,

(23)

n sumably for the same steric reasons which lead to the formation of (26) rather than the expected am-disilylated ylide. The same phosphorane with the dichlorodisilane (27) gave the cyclic bis-ylide (28), while the cyclic ylide (29) was obtained from (27) and trimethylsilylmethylenetrimethylphosphorane followed by butyl-lithium. 3 hlc, P C H ,

+ 2 Mc,Si.SiMe,C‘I (25)

C, -+ Mc,P,

H *, Si M c2-Si hl e:, CH-SiMc,-SiMe:,

+

(26) 2 Mc.,f’I (’I

PMe, I1 C hle,Si’ ‘SiMe, 6 Me,P:CH, + 2 C1Mc2Si-SiMc,CI -+ I I Me,Si, ,SiMe, (27) C I1

PMe, (28) l7

H. Schmidbauer and W. Malisch, Chem. Ber., 1970,103, 3448. H . Schmidbauer and W. Vornberger, Angew. Chent. Internat. Edn., 1970, 9, 737.

Ylides arid Related Compounds

155

(I)

hle,P:CH.SiMe,

(27)

(11) BuLi

1 “ ‘SiMe,

+ Me,P Nc,

I S i Me,

I SiMc, (?9)

A full account has appeared l* of the reactions of the ester phosphoranes (30; R3 = H) with acyl chlorides. Equimolecular proportions gave the salts (3 1) from which 15-ketoesters were obtained on electrolytic reduction. A 2 : 1 excess of phosphorane gave the allenic esters (32), presumably via the betaines (33).

The absolute configurations of carboxylic acids can be determined l 9 from the sign of rotation of the phosphonium salt precipitated when the corresponding acyl chlorides are treated with the optically active ylide (34) in THF. It is found that the sign of the specific rotation of the precipitated salt agrees with the sign of the chirality product x when the absolute configuration of the acyl chloride is as in (35). The chirality product is given by the equation:

where the ligand constants, A, are assigned as described by Ugi and Ruch.20

‘Lo

H. J. Bestmann, G . Graf, H . Hartung, S. Kolewa, and E. Vilsmaier, Chern. Ber., 1970, 103, 2194. H. J. Bestmann, H. Scholz, and E. Kranz, Amgrw. Chem. Iiiternat. Edn., 1970, 9, 796. E. Ruch and I . Ugi, Topics Stereochem., 1969, 4, 99.

Organophosphorus Chemistry

156

Me

M t:

I 2 Ph--P=CH.Pti 1 Pr (34)

+ R’K2RR:’C.COCI

7 I1F

I Ptl--P=CPti.CO.CK’K’RR“ I

Pr

hf c

Pr

(35)

(ii) Carbonyls. The stereochemistry of the Wittig olefin synthesis has been reviewed.21 trans-Stereoselective olefin synthesis via /3-oxido-ylides is possible only in the presence of soluble lithium salts.2a Protonation of p-oxido-ylides prepared from salt-free ylides leads to mixtures of erythroand threo-betaines and hence to mixtures of cis- and trans-olefins. Large concentrations of halide ions, preferably iodide, favour the formation of trans-stil bene from benzaldehyde and benzyltriphenylphosphoniunl halides in methanol with methoxide as base, whereas large concentrations of methoxide ions slightly favour formation of the ~ i s - i s o r n e r . ~These ~ effects have been explained by the preferential solvation of P+ by halide ions, leading to greater reversi bility of betaine formation. Methoxide ions, on the other hand, are preferentially solvated by methanol. The quality of phenyl-lithium used to generate ylides can have a pronounced effect on the stereochemistry of olefin synthesis. In the reactions of the ylide (36) with the aldehydes (37) cis-olefins were obtained using a phenyl-lithium solution containing one equivalent of total base while trans-olefins resulted from the use of an amount of this solution containing one equivalent of genuine phenyl-lithium together with six equivalents of other, unspecified, base.24

M . Schlosser, Topics Stereochem., 1970, 5 , 1. x M. Schlosser, K.-F. Christmann, and A. Piskala, Cheni. Ber., 1970, 103, 2814. z y T. Bottin-Strzalko, J . Seyden-Penne, and B. Tchoubar, Compt. rend., 1971,272, C,778. a 4 E. J. Reist and P. H. Christie, J . Org. Chem,, 1970, 35, 4127. z1

157

Yiides and Related Compounds

A polymer containing side-chain benzylphosphonium residues has been prepared and used in olefin synthesis.25 A suspension in THF was treated with base and benzaldehyde overnight and the polymeric phosphine oxide was then removed by filtration. The yields of stilbenes, 40% with potassium t-butoxide and 60% with sodium hydride, were not improved by using an excess of base or of aldehyde. The aldehyde group of laevulinic aldehyde reacted preferentially with the ester phosphorane (38),26 while the 2-acetyl groups of the benzofurans (39) were selectively methylenated 27 with methylenetriphenylphosphorane. The aldehyde group was protected as the dimethylacetal in the synthesis 28 of the steroidal a-methylene-aldehyde (40).

R

=

ti, OH. o r OMe

R

2

OH (73",,)

(39)

CH(OMe),

CHO

CO

C:CH,

I

I

(40)

The carbonyl group of the keto-acid (41) is remarkably unreactive2@ towards methylenetriphenylphosphorane. Only 10% of unsaturated acid was obtained using a large excess of reagent in DMSO at 58 "Cfor several days.

(41) 25

2R 27 2H

28

(43)

F. Camps, J. Castells, J. Font, and F. Vela, Tetrahedron Letters, 1971, 1715. A. J. Birch, J. E. T. Corrie, and G. S. R. Subba Rao, Austral. J . Chem., 1970, 23, 1811. J. A. Elix, Austral. J . Chem., 1971, 24, 93. W. Haede, W. Fritsch, K. Radschett, U. Stache, and H. Ruschig, Annalen, 1970,741,92. D. F. MacSweeney and R. Ramage, Tetrahedron, 1971,27, 1481 ; F. Kido, H. Uda, and A. Yoshikoshi, Chem. Comm., 1969, 1335.

Organophosphoriis C hernist ry

158

Scrambling of tritium was observed 30 in reactions of the bisphosphonium salt (42) with geranylacetone in t-butanol containing potassium t-butoxide. Recovered ketone had incorporated tritium and the resulting squalene had a maximum of 32.8% of scrambling. Scrambling in methylenation of the a-deuterioketone (43) was avoided 31 by using the ether (EtOCH2CH2)20 as solvent and butyl-lithium as base. The isomerization observed in the methylenation of cis-a-decalones has been turned to good advantage. Mixtures of cis- and trans-isomers of the a-decalones (44) 32 and (46) 33 gave only the trans-decalins (45) and (47).

(47)

(46)

Quantitative yields of allenes were obtained 34 from keten and the stable phosphoranes (48). Addition of similar phosphoranes occurred 35 at the p-position of the allenic ketones (49) to give the phosphoranes (50). The compound (50; R1 = COPh) eliminated phosphine oxide under the conditions of the reaction to give the acetylene (51).

+

c l r 2c:12

Ph,P:CR’R2 CH,:C:O + R1R2C:C: CH, (48; R1 = H or Me; R2 = CN, COR, or C0,Et)

2H-Pyran-2-ones were obtained 36 in low yield on heating p-diketones, e.g. (52), with the ester phosphorane (53) under severe conditions. In refluxing benzene the cyclopropenones (54) with the phosphoranes ( 5 5 ) gave 37 triphenylphosphine and the pyran-2-ones (58) (50%). At room so

D. H. R. Barton, G. Mellows, D. A. Widdowson, and J. J. Wright, J . Chem. Suc. (C), 1971, 1142.

81

3a 33 34

36 30

37

T. B. Malloy, jun., R. M. Hedges, and F. Fisher, J . Org. Chem., 1970, 35, 4256. J. W. Huffman and M. L. Mole, Tetrahedron Letters, 1971, 501. C. H . Heathcock and R . Ratcliffe, J. Amer. Chern. Soc., 1971, 93, 1746. Z. Hamlet and W. D. Barker, Syrrrhesis, 1970, 2, 543. G. Buono, G. Peiffer, and A. Guillemonat, Cumpt. rend., 1970, 271, C , 937. A. K. Soerensen and N. A. Klitgaard, Acta Chem. Scand., 1970, 24, 343. T. Eicher, E. v. Angerer, and A.-M. Hansen, Annafen, 1971, 746, 102.

Ylides and Related Compounds

159

temperature (54; R1 = Ph) and (55; R2 = OMe) also gave the normal Wittig product (57). The methylenecyclobutanes (60) were formed from the same phosphoranes and the methylenecyclopropene (59). The formation of the pyran-2-ones may involve the intermediate cyclobutenones (56) as shown.

5%

160

Organophosphorirs Chemistry

Zincke's aldehyde (61) and cyanomethyltriphenylphosphonium chloride in acetic anhydride at 100 "Cgave 38 the salt (62), isolated as the perchlorate, whereas the same reagents in pyridine gave the phosphorane-phosphonium salt (63), presumably via nucleophilic addition of cyanomethylenephosphorane to the terminal carbon of (62). PhNMeOCH: CH*CH:CH-CHO

+

Ph,Pi *CH,CN CI-

(61)

PhN Me*CH:CH : CH :CH*CH:C(CN)*P+Ph, (62) 1' y r i (1 i ti (!

1

1 L.T.

Ph,P: C(CN)-CH:CH*CH: CH-CH :C(CN)*P Ph, I (63)

The allylidenephosphorane (64) with phenanthraquinone gave 39 the pyran (65) together with small amounts of (66) and (67). Similar pyrans were also obtained from (64) and a-naphthoquinone and tetrachloro-obenzoquinone. Among other olefins prepared in conventional ylide reactions with carbonyls are (68),40(69),41(70),42and (71).43 38

Bp O0 41 42 43

A. V. Kazymov and E. B. Sumskaya, Zhur. org. Khirn., 1970, 6, 1944 (Chern. A h . , 1970, 73, 109 842). G. Cardillo, L. Merlini, and S. Servi, Ann. Chim. (Italy), 1970, 60, 564. B. Miller and K.-H. Lai, Tetrahedron Letters, 1971, 1617. J. Meinwald and D. A. Seeley, Tetrahedron Letters, 1970, 3739. J . Meinwald and D. A. Seeley, Tetrahedron Letters, 1970, 3743. M. I . Shevchuk, A. S. Antonyuk, and A. V. Dombrovskii, Zhrrr. org. Khitn., 1970, 6, 2579 (Chew. A h . , 1971,74, 64276).

YIides and Related Compounds

I61

g. I

/

CH,.CH,OH CH:C Me,

CH: C Me,

Ph:,t’: (‘Me,

CH:CMe,

P$P:CX*COR

+ ArCHO

PhMe

ArCH:CX-COR (71)

X = H, C1, Br, or I R = a-benzofuranyl or 3-dibenzofuranyl

162

Organophosphorus Chemistry

The formation of the naphthalene (73) from the bis-ylide (72) and diethyl ketomalonate 4 4 involves an unusual olefin synthesis on the carbonyl of an ester group. The methylene-pyrans (75) were formed46 when the diethyl malonates (74) were refluxed with /I-keto-ylides in xylene or decalin. Possible intermediates are the ketens (76) and the allenes (77). Addition of ylide to the allenes gives the betaines (78) which form methylene-pyrans either directly or via acetylenes as shown.

a

C H :P Ph,

+ (EtO,C),CO

CH :PPh,, (72)

2 Ph,P:CIi.C'OK'

-

m I E ;t (73)

+ R'CH(C0,Et)2

-+ 2 Ph3P0

R? = I1 o r M e

(55)

+ R1 (75)

(74)

/R'

Et02C liC=C, \ / 0C=C K'

I Et0,C

\

HC=C /

.

A

I-

pt':'''O

R' /

E l 01.c

\

\

HC=C,

c=c/

/

R' OH

(75) 44 45

W. H. Ploder and D. F. Tavares, Cunad. J . Chem., 1970, 48, 2446. H. Strzelecka, M. Dupre, and M. Simalty, Tetrahedron Letters, 1971, 617.

163

Ylides and Related Corripouiids

(iii) Miscellaneous. Symmetrical olefins were obtained Q6 from reactive ylides and sulphur under fairly vigorous conditions. Yields were high when R = Ar, but the ethylidenephosphorane gave only 28% of hex-3-ene at 150 “C in 1 -methylnaphthalene. Ph,P:CHR

+ S8

RCH:CHR

+ Ph,PS

The triazoles previously obtained from 6-keto-ylides and acyl azides or ethyl azidoformate are 47 the 2-acyltriazoles (80) formed by isomerization under the basic conditions of the initially formed 1-substituted triazoles (79). The latter can be isolated in some cases if the reactions are interrupted. Aryl mono- and bis-azides have also been used 4 s in the preparation of the triazoles (81).

I

H

R1

R2

N%N-Ar

The reaction between benzylidenetriphenylphosphorane and benzonitrile has been reinvestigated and the primary product (82) isolated. Stable ylides react similarly with activated nitriles, e.g. cyanogen and trifluoroacetonitrile, but cyanomethylenetriphenylphosphorane with methyl cyanoformate gave largely the vinyl ether (83), the product of a normal olefin synthesis on the carbonyl of the ester group. Diphenylcarbodi-imide reacts with ylides 50 to give, in general, the iminophosphorane (86) and the imines (85). The latter usually react with a second mole of ylide to give the stable phosphoranes (87) although the imine (85; R1 = R2 = Ph) was isolated. Hydrolysis of the solution M 41

O@

H. Mtigerlein and G . Meyer, Chem. Ber., 1970, 103, 2995. P. Ykman, G. L’AbbC, and G. Smets, Tetrahedron Letters, 1970, 5225. P. Ykman, G. L’AbbC, and G . Smets, Tetrahedron, 1971, 27, 845. E. Ciganek, J . Org. Chem., 1970, 35, 3631. Y. Ohshiro, Y . Mori, T. Minami, and T. Agawa, J . Org. Chew?., 1970, 35, 2076.

164

Organophosphorus Chemistry

resulting from treatment of the carbodi-imide with methylenetriphenylphosphorane in DMSO gave the amidine (88), presumably formed via proton transfer in the intermediate (84; R1 = R2 = H).

J

Ph,P:N-C(CN):CH.CN 2 isomers

(c”Y Ph,P:CH.CN (h Me(),(-.

Ph,PO

+ NC.CH:C(OMe).CN (83) -t

Ph,P:C R’K’ + PhN:C :NPh +Ph3P-C R’R2 PhN-&:NPh (84)

R* = R? =

[Ph,P:CH.C ( N HPh) :NPh]

I

/ I

Ph,P:NPh

H,O

Me(NHPh):NPh

+ Ph,PO

(86)

+ R’R2C:C:NPh (85)

I PIi,P:CR’-C (CH,R’):NPh

(87)

Ethylidenetriphenylphosphorane and N-methyl-N-phenylthioacetamide (89) in THF gaveK1a suspension from which the vinyl thio-ethers (91) were obtained on treatment with carbonyl compounds. The suspension O1

T. Mukaiyama, T. Kumamoto, S. Fukuyama, and T. Taguchi, Bull. Chem. SOC.Japan, 1970,43, 2870.

Ylides and Related Compounds

165

was probably the salt (90) in equilibrium with the phenylthio-ylide. Methylenetriphenylphosphorane with the same reagent (89) gave the bis(pheny1thio)-ylide (92). Ph,P:CH Me

+ PhS-NMe-COMe -+Ph,&CHMe-SPh (89)

(90)

+ (89) --+

Ph,P:CH,

MeN-COMe

Ph,P:C(SPh), (92)

Vinylsulphonium salts and ylides gave 6 2 cyclopropylphosphonium salts (95) via proton transfer in the initial adducts (94). C-Methylation of the

ylides also occurred with dimethylvinylsulphonium salts, whereas the ylides (93; R1 = H, COPh, or p-NO,*CBHI) gave only the corresponding phosphonium salts.

+

Ph,P.CHMeR' X+

Ph,P:CHR' (93)

u2*

u'

=

+ K2CH:CH.SR3R4 X-

R'

\

= 14.

+

+ R2CH:CH.SMe

COPh. p-NO,.C,HI

i-

+ Ph3P.CH,R1 X-

Ph3P*CHR1 R2&H.CH. i R 3R4 (94)

I

A normal olefin synthesis took place53 between a carbonyl ligand of bromopentacarbonylmanganese and hexaphenylcarbodiphosphorane to give an organometallic ylide. ba

bs

R. Manske and J. Gosselck, Tetrahedron Letters, 1971, 2097. D. K. Mitchell, W. D. Korte, and W. C. Kaska, Chem. Comm., 1970, 1384.

I66

Organophosphorirs Chemistry Ph,P:C:PPh,

+

MnBr(CO),

('sllo, Mn(CO),Br(:C:C: PPh,) 4 0 "C'

Semi-empirical molecular orbital calculations have been carried out 64 on the model phosphorane H3P:CH2. Besides the expected transfer of charge, the inclusion of the phosphorus 3d orbitals showed a significant hyperconjugative interaction between the CH2 orbitals and a 3d orbital of appropriate symmetry on phosphorus. Calculations on cyclopropylidenephosphorane revealed 65 a similar interaction between the Walsh orbitals of the ring and an in-plane phosphorus 3d orbital. For the n.m.r. spectra of /3-keto-ylides see Chapter 1 I , and for their photolysis see Chapter 10.

2 Phosphoranes of Special Interest A kinetic investigation 66 of the reaction between cyclopentadienylidenetriphenylphosphorane (96) and tricyanovinylbenzene to give the phosphorane (97) has identified the slow step as nucleophilic attack of the phosphorane on the olefin. This is then followed by a rapid intramolecular proton transfer. An Elcb mechanism has been postulated 67 for the basecatalysed elimination of hydrogen cyanide from (97), rapid proton loss giving an ion-pair from which cyanide ion is lost in the rate-determining step. The reactions between the phosphorane (96) and a series of benzylidenemalononitriles have also been carefully investigated 6H and a mechanism proposed involving n-complex formation between the phosphorane and the cyano-olefins. Semi-empirical molecular orbital calculations on the phosphorane (96) p h l P/ O

(96)

6K 66

67

6R

+ PhC(CN):C(CN),

'Q

d Ph,P

PhC (CN )

- c (CN

12

R. Hoffman, D. B. Boyd, and S. Z. Goldberg, J. Amer. Chem. SOC., 1970, 92, 3929. D. B. Boyd and R. Hoffman, J. Amer. Chem. SOC.,1971, 93, 1064. E. Lord, M. P. Naan, and C. D. Hall, J. Chem. SOC.(B), 1970, 1401. E. Lord, M. P. Naan, and C. D. Hall,J. Chem. SOC.(B), 1971, 220. E. Lord, M. P. Naan, and C. D. Hall, J. Chem. SOC.( B ) , 1971, 213. Z. Yoshida, K. Iwata, and S. Yoneda, Tetrahedron Letters, 1971, 1519.

YIides and Related Compounds

I67

and its U.V.spectrum show that in the ground state it has 88% of P+-C character and 12% of P: C character. This is not due to aromatic stabilizaion of the cyclopentadiene anion, as calculations on the rnethylene ylide give a similar result. The phosphorane (96) readily undergoes electrophilic substitution at the 2-position and adds to electrophilic olefins also at this position.s1 Thus, nitration with ethyl nitrate and aluminium chloride or with nitronium borofluoride gave the 2-nitrophosphorane (98), Vilsmeier formylation gave the 2-aldehyde (99), and diethyl acetylene dicarboxylate gave the phosphorane (100). No Diels-Alder adduct was obtained from (96).

Ally1 vinyl ethers have been prepareds2 using the ylide (101) but only from non-enolizable carbonyl compounds. The ethers rearrange on heating to give a-ally1 aldehydes, e.g. (102).

I

Ph<'llO

5.

PhCH (C 1-10}-CH,*Cl I:CH, (102) (70:; O0

62

f--

PhC H:CH*O-CH,*C H :C H,

ovcrall)

Z. Yoshida, S. Yoneda, Y. Murata, and H. Hashimoto, Tetrahedron Letters, 1971, 1523. Z . Yoshida, S, Yoneda, H. Hashimoto, and Y . Murata, Tetrahedron Letters, 1971 1527. E. J. Corey and J. I. Shulman, J . Amer. Chem. SOC.,1970, 92, 5522.

I68

Organophosphorus Chemistry

Full details have appeared 63 of the generation and use in synthesis of the chlorofluoromethylene-ylide (I 03). Fluoromethylenetriphenylphosphorane (104) has been prepared as shown 64 and among other unusual ylides used in normal olefin synthesis are (105),s5(106),6s (107),ss(108),67 and (109)? The latter gave acyclic phosphine oxides (1 10) in up to 50% yield.

Ar

M C,

O3 64 O5

e7

Al-

I

D. J. Burton and H. C. Kruzsch, J. Org. Chem., 1970, 35, 2125. M. Schlosser and M. Zimmermann, Synthesis, 1969, 1, 75. M . Schlosser and A. Piskala, Synthesis, 1970, 2, 22. M. J. Berenguer, J. Castells, R. M. Galard, and M. Moreno-Mafias, Tetrahedron Letters, 1971, 495. J. A. Eenkhoorn, 0. S. de Silva, and V. Snieckus, Chem. Comm., 1970, 1095. D. Lednicer, J . Org. Chem., 1970,35, 2307.

Ylides arid Related Compounds

169

The seven-membered exocyclic phosphorane (1 11) with the fluorenealdehyde (1 12) gave triphenylphosphine and the aldehyde (1 14) instead of the expected ~ l e f i n .Compound ~~ (1 14) could have been formed as shown, the phosphorane functioning as a base to generate the anion (1 13).

+

+

Xh3

3m

4vvvw-P

1

( I 13)

(1 14)

Methoxy-olefins were obtained 'O when the allenic phosphonium salt (1 15) was used in olefin synthesis with sodium methoxide as base. Sodium t-butoxide gave the enynes (1 16) except with p-nitrobenzaldehyde from which the cumulene (1 17) was formed. I

-

PhCH: C (OMe) CH:CHR

PhCiCCH:CHR (116)

PhCH:C:C:CH*C6H,N02-p ( 1 17) RR

L. Salisbury, J . O r g . Client., 1970, 35,4258. H . Saikachi, N. Shimoyo, atid H . Ogawa, Ydugtrktr Zosshi, 1970, 90, 581 (Chew. Ah.%., 1970, 73, 35 456).

0rganophosphor its Cheniistry

170

3 Selected Applications of the Wittig Olefin Synthesis

A. Natural Products.-(i) Carotenoicis. Corey has now applied his stereospecific synthetic route 7 1 to trisubstituted olefins via p-oxido-ylides to the synthesis 7 2 of C17- and C18-Cecropiajuvenile hormones and related compounds. Ethylidenetriphenylphosphorane on successive treatment with butyl-lithium, the aldehyde (118) at - 78 "C, butyl-lithium, and formaldehyde gave the pure alcohol (1 19). This was converted as shown into the phosphonium salt (120) which in a /3-oxido-ylide synthesis using the aldehyde (1 2 1) and formaldehyde gave the unsaturated alcohol ( 1 22) free from stereoisomers. This alcohol was then used in the synthesis of dl-C,, and d/-C18juvenile hormones. s-Butyl-lithium i n T H F is the reagent of choice for the generation of /?-oxido-ylides from Wittig betaines.

-

p o ( 1 , 1'11,i' l 1 C'11Mc

C'HO

_((_ 11 11 1_ ) 1 13111 c II:O I

( I IS)

G H o I H (

GI;)''

I 19) (hO",,) l'tlS1'

(

11:

CH,O I

The p-oxido-ylides synthesis of trisubstituted olefins has also been applied 73 to the synthesis of farnesol (127). The phosphonium salt (123) with the aldehyde (124) and formaldehyde gave the hydroxy farnesol derivative (125) which was transformed into farnesol (1 27) and into ( I 26), a position isomer of CI7juvenile hormone. 71

72

7:1

'Organophosphorus Chemistry', ed. S. Trippett, (Specialist Periodical Reports), The Chemical Society, London, 1971, Vol. 2, p. 165. E. J. Corey, H. Yamamoto, D. K. Herron, and K. Achiwa, J . Amer. Cherii. Soc., 1970, 92, 6635; E. J. Corey and H. Yamamoto, ibid., p. 6636. E. J. Corey and H. Yamamoto, J . Amer. Chetn. Soc., 1970, 92, 6637.

Ylides and Related Compounds

171

HOH2C CH@n

+ CH,O

---+

CHO '

(

125) (46",,) II

V

k'

(127)

( 126) ,/'\.,

11

-

j

1

trans-p-Sinensal ( 1 29) has been obtained '* from the aldehyde ( 1 28) as shown. The aldehyde was formed on selective ozonolysis of transfarnesenes.

A number of keto-carotenoids have been prepared 7 5 from the bisphosphonium salt ( 1 30) and substituted CIS-aldehydes,the keto-functions " 7u

Swiss P. 493 451 (Chern. Abs., 1970, 73, 120 775). J. D. Surmatis, A. Walser, J. Gibas, U. Schwieter, and R. Thommen, Helv. Chirn. A d a , 1970, 53, 974.

172

Organophosphorus Chemistry

being protected as ethylene acetals or as vinyl ethers. Illustrated is the synthesis of an unsymmetrical keto-carotenoid (131) from (130) and a mixture of aldehydes. Keto-carotenoids with the keto-groups incorporated in the unsaturated chain have also been obtained, e.g. (1 32).

(I)

PhLi-Et,O

(ii) 11+

Zeaxanthin (135) was synthesized 76a from the salt (133) and the dialdehyde (134) in 1,2-epoxybutane, a reagent superior to ethylene oxide particularly for polyenedialdehydes. The same salt was also used to prepare p-cryptoxanthin and zeinoxanthin. Phenolic carotenoids 76b from Streptomyces rnediolani and 1,2-dihydro- and 1,2,1',2'-tetrahydro-lycopene 76c have also been obtained by conventional olefin synthesis. D. E. Loeber, S. W. Russell, T. P. Toube, B. C. L. Weedon, and J. Diment, J. Chern. Suc. (C), 1971, 404. F. Arcamore, B. Camerion, G . Franceschi, and S. Penco, H. Kjoesen and S. Liaaen-Jensen, Acta Chem. Scand., Gazzerra, 1970, 100, 581.

1970, 24, 2259.

Ylides and Related Compounds

173 I

I

100 "C

J

(ii) Prostaglandins. Stereospecific total syntheses of prostaglandins E3 and F,, have appeared.77 The (S)-(+)-phosphonium salt (136) with methyllithium gave the p-oxido-ylide (137) which with the aldehyde (138) gave the alcohol (139). The sequence shown led to the hydroxy-acid (140) from which prostaglandin F3cy was obtained on removal of the protecting groups. The salt (136) was prepared as shown from the aldehyde (141), itself obtained from (S)-(- )butane-l,2,4-triol. Wittig olefin syntheses have also been used in syntheses of (k )-A8(12)-15dehydroprostaglandin El 78 and of ( k )-prostaglandin In the course of the latter, coupling of the salt (142) with methyl 6-formylheptanoate followed by acid-catalysed isomerization gave the ester (143). (iii) Miscellaneous. The predominant formation of cis long-chain olefins has been applied to the synthesis of crepenynic acid (144),*O cis-capsaicin ( 1 4 y cis-jasmone (146),82and the pheromone ( 147).83 The widely varying conditions leading to cis-olefins are remarkable. In the course of a synthesis 84 of (+)-nootkatone the keto-ester (148) with ethylidenetriphenylphosphorane gave the cyclohexanone ( 149), a Dieckmann condensation having occurred under the basic conditions. Among other natural products synthesized using Wittig reagents are 77

79

no

R1

E. J. Corey, H. Shirahama, H. Yamamoto, S. Terashima, A. Venkateswarlu, and T. K . Schaaf, J . Amer. Chem. Soc., 1971, 93, 1490. M. Miyano, C. R. Dorn, F. B. Colton, and W. J. Marsheck, Chem. Comm., 1971, 425. D. Taub, R. D. Hoffsommer, C. H. Kuo, H . L. Slates, Z. S. Zelawski, and N. L. Wendler, Chem. Comm., 1970, 1258. R. W. Bradshaw, A. C. Day, E. R. H . Jones, C. B. Page, V. Thaller, and R . A . Vere Hodge, J . Chem. SOC.( C ) , 1971, 1156. R. Rangoonwala and G . Seitz, Deut. Apotheker-Z., 1970, 110, 1946 ( C h e m . A h . , 1971, 74, 99 541).

ws 84

B.P. 1 202 343 (Chem. Abs., 1970, 73, 120 490). H . J. Bestmann, P. Range, and R . Kunstmann, Chem. Ber., 1971, 1 0 4 , 6 5 . J. A, Marshall and R. A. Ruden, J . Org. Chem., 1971, 36, 594.

174

Organophosphorus Chemistry

LHW

01I

I 1 0 H

.

.

(70"")

1'11

I'

(136) I ICH,

H

-

O

T

Ylides and Related Compounds

175

(CH, ),.CO,Me

+

-

Mc(CH,),C~C.CH,.CH,.PPh, Br

+ OHC.(CH,)i.CO,Me

lc (1)

(11)

HUI 011

I

It-0

~

M e (CH,) Ci C .CH,*CH :CH-(C H, ) ;*CO,H (144) (SI]',,ot'c\tcr.)

Ph,6-(CH,),.CN Br-

+ Me,CH.CHO

N OMe

I;Lhl,

(*

Me,CH-CH:CH.(CH,),.CN ( 8 5" [,)

176

Organophosphorus Chemistry

piperovatine,85 d- and Z-sirenin,8s the polyene (150) from the alga Fircus vesiculosus,87and ( f )-presqualene alcohol.8X Methylenation of carbonyls has become a routine operation and these are not mentioned unless they have features of special interest MCO,C’,,

,c

Mc 0

0

, , /

0 (139) (401‘:)

(1 48)

Me(CH,)

3 - (CH,.CH:CH),-

,CMC,

+

(CH,) 3-CH2.PPhjBr-

( 150)

B. Macrocyc1ics.- -Full details have appeared 89 of the synthesis of the bicycl o [6,2,0]decapentaene (152). Benzocyclobu tanedi one and the bi s-yli de (1 53) gave only acyclic compounds. The dibenzocyclononatetraene (1 55) has been obtained from the dialdehyde ( I 51) and the bis-ylide (1 54). The bis-phosphonium salt (156) has been condensed with various dialdehydes to give potentially aromatic and anti-aromatic systems, while fully unsaturated 11- (158), 12- (1 59), and 13-membered (160) sulphur heterocycles have been prepared as These showed no appreciable ring current and are presumably non-planar. Cyclopentene, cyclohexene, and cycloheptene were obtained by intramolecular oxidative couplings of the bis-ylides (161; n = 3, 4, or 5 ) but oxidation of (161; n = 2) gave cyclo-o~ta-l,5-diene.~~ Oxidation of the bis-ylide (161 ; n = 8) gave cyclic polyenes containing 20, 30, 40, 50, and 60 atoms. nL

x7

O0 O1

82 O5

S. J. Price and A . R. Pinder, J . Org. Chem., 1970, 35, 2568. U. T. Bhalerao, J. J. Plattner, and H. Rapoport, J . Amer. Chem. Suc., 1970, 92, 3429. T. G . Halsall and I. R. Hills, Chem. Comm., 1971, 448. R. M. Coates and W. H. Robinson, J . Amer. Chem. Suc., 1971, 93, 1785. A . A. Shamshurin, D. G. Kovaler, and A. P. Donya, DukIudy Chem., 1970, 190, 169. ‘ G . Pattenden, J . Chem. SOC.( C ) , 1970, 1404. P. J . Garratt, K. P. C. Vollhardt, and R. H. Mitchell, J . Chem. SUC.( C ) , 1970, 2137. P. J . Garratt and K . A . Knapp, Chem. Cumin., 1970, 1215. J . A . Elix, M . V. Sargent, and F. Sondheimer, J . Amer. Chpm. Sor., 1970, 92, 973. A. B. Holmes and F. Sondheimer, f. Amer. Chem. Soc., 1970, 92, 5284. H. J. Bestmann and H. Pfuller, unpublished data reported in H. J. Bestmann, Bid/. SUC.chim. France, 1971, 1619.

I77

Ylides and Related Compounds

2 Rr\D

M F-T:t 0 1 I

178

Organophosphorus Chemistvy

CH:PPh, I (CH,),

I

CH:PPh,

C. Miscellaneous.-Among ylides, Ph3P:CHR, used in conventional olefin synthesis with protected keto-sugars are those with R = H,04 CN,85SMe,9s and COR.g7 Optically pure quinic and shikimic acids have been synthesized 9* starting from D-arabinose. The key steps involved treatment of the bistosylate (162) with 3 rnol of methylenetriphenylphosphorane to give the ylide (163) which with formaldehyde gave the olefin (164) in 82% yield overall. The stilbenes (165) loo and (166) lol were prepared as shown. Polyhydroxystil benes, e.g. (1 67), were obtained lo2 using dihydroxybenzalA. Rosenthal and M. Sprinzl, Canad. J . Chern., 1970, 48, 3253. J. M. J. Tronchet, J.-M. Bourgeois, J.-M. Chalet, R. Graf, R. Gurny, and J. Tronchet, Helu. Chim. Acta, 1971, 54, 687. J. M. J. Tronchet and J. M,Bourgeois, Helu. Chim. Acfa, 1970, 53, 1463. Yu. A. Zhdanov, L. A. Uzlova, L. P. Leskina, and 0. A. Gavrilenko, Zhur. oshchei Khim., 1970,40, 666 (Chem. Abs., 1970,73, 25 772). H. J. Bestmann and H. A. Heid, Angew. Chem. Internaf. Edn., 1971, 10, 336. G. Jones and S. Wright, J . Chem. SOC.( C ) , 1971, 141. l o o W. Bell, D. Holland, and G . Jones, J . Chem. SOC. (0,1971, 143. I o l H. Blaschke, C. E. Ramey, I . Calder, and V. Boekelheide, J . Amer. Chem. Soc., 1970, p5

92, 3675. lop

E. Reimann, Tetrahedron Letters, 1970, 405.

YIides and Related Compounds

179

dehydes protected with triinethylsilyl groups. The stilbazole ( 1 68) was prepared lo3as shown.

”-/---: R

+ 3Ph,P:CH,

=

--+

PPh,

CH,Ph

0, xylcne

0 0

MeOCH, \

CH:CH \

CH,OMe

OH

OH lo8

( 167) V. Boekelheide and W. Pepperdine, J . Amer. Chem. SOC.,1970, 92, 3684.

180

Organophosphorus Chemistry

4 Synthetic Applications of Phosphonate Carbanions A study of the decomposition in basic media of the erythro- and threoisomers of the p-hydroxyphosphonate (169) showed lo4 that the first step in the phosphonate olefin synthesis is reversible and that the diastereoisomers of (1 69) can also interconvert directly, presumably via the a-carbanion. (EtO),P(: O)*CH(CN)*CH(OH)Ph (1 69)

(EtO),P(: O)*CH,R (170)

Among phosphonate esters (1 70) used in olefin synthesis were those with R = S.CeH4. Br-p,lo5SO2*CsH,- Br-p,lo5 CO. NHR,lo6and S. CH,. CH: CH2.S2 The ally1 vinyl thio-ethers (171) obtained using the last of these gave a-allyl-aldehydes on pyrolysis in the presence of red mercuric oxide.

lo4 Io6

G. Lefebvre and J. Seyden-Penne, Chem. Comm., 1970, 1308. I. Shahak and J. Almog, Synthesis, 1970, 2, 145. I. Shahak, J. Almog, and E. D. Bergmann, Israel J. Chem., 1969, 7, 585.

YIides and Related Compounds

181

Enamine phosphonates (1 72) have been prepared by the addition of amines to alkynylphosphonates and used as shown in the synthesis of ap-unsaturated ketones.lo7 The corresponding diphenylphosphine oxides have been prepared and used in a similar rnanner.lo8 (Et0)2P(:O)CiCK1 t K ' N H , --+ (r'rO),P(:O).CH:CRl.NHR' (

172)

Corey's phosphonamide olefin synthesis has been extended lo9 to the synthesis of vinyl ethers using the phosphonamides (Me,N),P(: 0)-CH'OR. A new pteridine synthesis is based on the reaction of 4-amino-5-nitrosopyrimidines with the phosphonate carbanions (173; R1 = C02Et,1101l l 1 CN,ll1or CORS1ll).

Benzylphosphonates have been used in the synthesis of polymethoxystilbenes 112 and of (1 74) 113 and (1 75).11' The hydrocarbon (1 75) obtained in this way was much easier to purify than that prepared using the bisphosphonium salt. lo'

lo*

'lo 11*

M. S . Chatta and A. M. Aguiar, Tetrahedron Letters, 1971, 1419. N. A. Portnoy, C. J. Morrow, M. S . Chatta, J. C. Williams, jun., and A. M . Aguiar, Tetrahedron Letters, 1971, 1401. G. Lavielle and D. Reisdorf, Compr. rend., 1971, 272, C, 100. R. D. Youssefyeh and A. Kalmus, Chem. Comm., 1970, 1371. E. C. Taylor and B. E. Evans, Chem. Comm., 1971, 189. F. W. Batchelor, A. A. Loman, and L. R. Snowdon, Canad. J . Chem., 1970, 48, 1554.

E. Muller, M. Sauerbier, D. Streichfuss, R. Thomas, W. Winter, G . Zountsas, and J. Heiss, Annalen, 1970, 735, 99. J. Meinwald and J. W. Young, J . Atner. Chetn. SOC., 1971, 93, 725.

lls

7

182

D M T NaOMe

______, J'hC 1iO

&'

*'

(

/

17.5) (40",,)

The phosphonate (176) has been used 115 for the addition to aldehydes of a masked /3-keto-ester function and applied in the synthesis of ( ? )-7(r),9(c)-trisporic acid B methyl ester. The isomerically pure phosphonate (177) has been used in a synthesis of dehydro-C,, juvenile hormone,*16the anion being generated by treatment with lithium di-isopropylamide in THF-HMPT at - 65 "C for 1 min.

Meo2cXMe Ii CH,.P(:O)(OEt), (

177)

The diketones (178; n = 0, 2, 4, 6, or 7) reacted normally with the phosphonate anion (1 79) to give unsaturated kefo-esters.ll7 However, lls

J. A. Edwards, V. Schwarz, J. Fajkos, M. L. Maddox, and J. H . Fried, ChPm. Cornrn.,

116

E. J. Corey, J. A. Katzenellenbogen, S. A. Roman, and N. W. Gilman, Tetrahedruir

117

Letters, 1971, 1821. B. G. Kovalev, E. M. Al'trnark, and E. S. Lavrinenko, Zhur. org. Khim., 1970, 2187 (Chenr. A h . , 1971, 74, 41 827).

1971, 292.

183

Ylides nnd Reln fed Compounds

acetylacetone gave only its enolate anion and the diketone (178; n = 5 ) underwent intramolecular aldol condensation. The same phosphonate anion with glutaric dialdehyde gave the cyclohexenol (180) as shown,*18 and the nitrile phosphonate behaved similarly. Normal olefin synthesis with the phosphonate anion (179) has become a routine reaction and only examples having features of unusual interest will be recorded. MeCO-(CH,);COMe

+ ( Et0)2P(:O).CH.C0,Et (179)

(178) I?

OHC.(CH,),*CHO

+ (179)

= 0, 2 . 4 . 6 7

4 McCO.(CH,),;CMe:C~-~.CO,E1

---+ t : I OHC9

0

-

Ol~C/-lOH

+

HC

/\

(EtO),P:O C0,Et

/"\

(EtO),P:O C 0 , E t

5 Ylide Aspects of Iminophosphoranes A general synthesis of the secondary amines RNHMe and RNHEt has been developed 119 starting from the iminophosphoranes (1 81). Alkylation with methyl or ethyl iodides (all other halides gave olefins) gave the salts ( 1 82) from which secondary amines were obtained on alkaline hydrolysis.

Ph3P:NR' i- R21 ---+ (181)

+

Ph3P.NR1R2 1(182)

R1 = alicyclic

1

EiOtI KOIi

R'R'NH

+ Ph,PO

(65- Q30,,) IlR

B. G. Kovalev and N . P. Dormidontova, J . Gen. Cheni. (U.S.S.R.), 1970, 40.910. H. Zimmer, M. Jayawant, and P. Gutsch, J . Org. Cheni., 1970, 35, 2826.

184

Organophosphorus Chemistry

The iminophosphoranes ( I 81) with imide bromides gave l Z o the amidinophosphonium bromides (1 83) which, it appears from their temperaturevariable n.m.r. spectra, are interesting fluxional molecules. The free energy of activation for the interconversion of (183a) and (183b) (Rl,R2 = Pr ; R3 = Ph) is 17.2 k 0.9 kcal mol-l.

K‘

(181)

+ K 2 N : C B r R 3 --

I +,N\ + Ph,P C-R:’ Br-N+ I K2

(183a)

R’ I

+

Pti,P,

N, N

,C-R3

f3r

(183h)

trans-Silylation occurs on treatment of silyliminophosphoranes with polyhalogenosilanes.‘21 The resulting irninophosphoranes (1 84) may exist as such or dimerize to give the salts (186) previously prepared lZ2 from the bisiminophosphorane (1 85 ; R = Me) and dihalogenodirnethylsilanes.

Mt..Si ’ N I1 I’Me, L...

lP1

+ X,SiM 1

T. Winkler, W. Von Philipsborn, J. Stroh, W. Silham, and E. Zbiral, Chem. Comm., 1970, 1645. W. Wolfsbergcr, H. H. Picker, and H. Schmidbauer, J . Organotnetallic Chem., 1971, 28, 307. W. Wolfsbergcr and H . Schmidbauer, J . Orgcitiotnetnllic Cherrt.. 1971, 28, 301.

Ylides and Related Compoirnds

185

Mixtures of a-phenyliminoesters (1 87) and the tautomeric enamines (1 88) resulted lZ3 from the reaction of phenyliminotriphenylphosphorane with a-keto-esters.

+ R'R'C:C(NHPh)*CO,EI (188)

Oxazoles (191) are produced 124 when triphenylphosphine is treated simultaneously with an a-azidocarbonyl compound and an acyl halide. The intermediate iminophosphoranes (1 89) react with the acyl halide before they can react with themselves to give pyrazines. Elimination of phosphine oxide from the resulting salts may give the intermediate halogenoimines (190), or the oxazoles may be formed via the betaines (192).

K' -- ti o r Me KS = Ar or OK

Trifluoroacetonitrile and the iminophosphorane (193) gave 4g the adduct ( 195) presumably via the four-membered intermediate (1 94). lz3

C. Shin, H . Ando, and J. Yoshimura, Bull. Cham. Sac. Japan, 1971, 44, 474.

lZ4

E. Zbiral, E. Bauer, and J. Stroh,

Monarsh., 1971, 102, 168.

186

-

Organophosphorus Chemistry

Ph,P:N.N:CPh2

+ CF3.CN

(193)

Ph,P:NC(CF3):N.N:CPh2 +--(195)

+

Ph3P-N.N:CPh2 i N=C*CF,

[

1

Ph3P-N .N :C Ph2 lyLl N=CCF, (194)

For the formation of iminophosphoranes from triphenylphosphine and a-bromo-a-cyano-succinimides see Chapter 1 , Section 2C.

9 Phosphazenes BY R. KEAT

1 Introduction One of the most significant developments in phosphazene chemistry during the past year has been the reported' application of alkoxycyclophosphazenes, [NP(OR)2]3,a,as flame retardants in rayon. This development has, in turn, provided a stimulus for improvements to be made in the largescale production of chlorocyclophosphazenes. Interest in the properties of the monophosphazenes has again increased considerably. An important comprehensive review of the cyclophosphazenes (including dimeric monophosphazenes) has appeared.

2 Synthesis of Acyclic Phosphazenes A. From Amides and Phosphorus(v) Halides.-The Kirsanov reaction remains one of the most important routes to acyclic phosphazenes; some recent examples of this reaction are summarized below: n-C4FB.S0,.NH, Rl-CO-NH,

i

+ PCI,

+ R2PCI,

R' = CHCI, CCI,

110 "C

4&60

CF,

"C:

n-C,F,.SO,.N=PCI, R1.C0.N=PCI,R2

CHCI, CCI,

CF,

+ 2HCI (ref. 3)

+ 2HC1 (ref. 4)

1

R2 = CH,CI CH,CI CH,Cl CHCI, CHCI, CHCI, The latter group of compounds are thermally unstable, giving RlCN and R2P(0)CI, at 60-150 "C. As expected, solvolysis occurs with water, formic acid, and methanol giving R'. C O . NH. P(0)(R2)0H, R1.CO*NH.P(0)(R2)Cl, and R1.CO*NHP(0)(R2)0Me respectively. Other amides react similarly: Ar.CH=C(CN).CO-NH,

goo(' > ArCH=C(CN)-CO- N=PCI, + PCI, y+ 2HCI (ref. 5)

(Ar includes aryl groups with C1, NO,, Me, or OMe substituents)

"

L. E. A. Godfrey and J. W. Schappel, Ind. and Eng. Chetn., Product Res. and Development, 1970, 9, 426. I. Haiduc, 'The Chemistry of Inorganic Ring Systems,' Wiley-Interscience, London, 1970, Part 2, p. 624. H. W. Roesky, Inorg. Nuclear Chem. Letters, 1970, 6 , 807. V. A. Shokol, V. F. Gamaleya, and V. P. Kukhar', Zhur. obshchei Khim., 1970, 40, 554 ( J . Getz. Chem. (U.S.S.R.), 1970, 40, 5201. V. I . Shevchenko, M. El Dik, and A . M. Pinchuk, Zhur. obshchei Khitri., 1970, 40, 1949 [ J . Gen. Chem. (U.S.S.R.),1970, 40, 19341.

188

Orgntiophosphorrrs Chemistry

An interesting feature of the i.r. spectra of these compounds was that the intensity of the C=N absorption was relatively low and, to account for this, an interaction of the type shown with (1) was suggested. With phos-

(1)

phorus pentachloride at 130-140 "C, the carbonyl group in (1) may be converted into a dichloromethylene group :

+

(1)

+ POCI,

ArCH=C(CN).CCI,-N=PCI,

PCI,

Monophosphazenes may also be obtained 13 by elimination of hydrogen fluoride in the presence of a tertiary base: PhPF,

+ XNH, + 2Et3N

------+

PhPF,=N*X

+ + 2Et3NH F-

(X = PSF,, PSFCI, PSCI,, SO,NH,, or N,P,F,)

Diamides, R(CONH,), [R = -CC12-, -CCI,(CH,),,,CCI,-], phazenes in a predictable manner :' R(CONH,),

+ 2PC1,

PhMe

R(CO-N=PCI3),

A

8G-100O

C

give diphos-

+ 4HCI

The products were further characterized by their hydrolysis [initially to R(CONHPOCI,),], aminolysis, alcoholysis, and thioalcoholysis products. The products of the Kirsanov reaction are not always those expected. For example, the following reaction* might be expected to give (2), but on the basis of i.r., 31Pn.m.r., and 35CC1n.q.r. spectroscopy, the product was the isomer (3): 0

Mc,I II Mc.

CI/P-N

c1

// =p-c' \

CI

MeP(O)(OEt)NH,

+ 2PCI,

---+

0

c'1

I1 /- c-1, P-N=P-Me I1 -N=P-Me /

C'I

/\

<,I'

CI

[(2)]

+ POCI, + EtCl + 2HCI

I (3)

'

H . W. Roesky, Z . Naturforsch., 1970, 25b, 777. V. P. Rudavskii, N. A. Litoshenko, and V. P. Kukhar', Zhur. obshchei Khim., 1970, 40, 1002 [ J . Gen. Chem. (U.S.S.R.), 1970, 40,9871. V. A. Shokol, G. A. Golik, V. T. Tsyba, and G. I. Derkach, Zhur. obshchei Khim., 1970, 40,931 [ J . Chem. Gem. (U.S.S.R.), 1970, 40, 9091.

Phosphazeries

189

This result also follows from that reported last year where alkyl groups were found to be most favourably bonded to phosphazenyl-phosphorus atoms rather than phosphoryl-phosphorus atoms, and means that revision of a number of previously reported structures is necessary. In some cases, the Kirsanov reaction may be modified so that an excess of the amine removes the hydrogen chloride formed: (CCI,),PCI,

+

+ 3RNH2

2RNH3Cl-

+ (CCI,),CIP=N-R

(R = Me, Et, Pr’, Bu”, or cyclo-C,H,,)

In all cases the products appeared to be monomeric and on hydrolysis gave a series of compounds, (CCI,),P(O)NHR. Although hydrazine monohydrochloride and phosphorus pentachloride give the bistrichlorophosphazene, CI,P= N . N = PCI,, an analogous product cannot be obtained with Ph,PCI,. Instead, a complex reaction occurs lo in which nitrogen and hydrogen chloride are eliminated, leaving a previouslycharacterized linear phosphazene:

+ 3N,H4,HCI

8Ph,PCI,

4[Ph,PCI.N=PCIPh2]+CI-

+ N, +

15HC1

This product was cyclized by NN’-bis(trimethylsilyl)hydrazine to give (4) :

[Ph,PCl- N = PCIPh,] +CI-

+

M e,Si * NH NH SiMe,

-----+ (4)

+ 2Me3SiC1

Few examples of N-(phosphino)phosphazenes, R,P. N= PR,, are known, but aminophosphines with P-perfluoroalkyl substituents have now been converted l1 into N-phosphinophosphazenes by reaction with phosphoranes in the presence of triethylamine: RZPNH,

+ CI,PXX’2 + 2Et3N

R = C3F7 CF, x = CI Cl*

X1 = C1

Ph

---+ R,P-N=PXX’,

C3F7 CF, c1* c1*

C,F, CI

Ph

Et

Et

+ 2Et,NHC1

1

E. S. Kozlov, S. N. Caidamaka, and A. V. Kirsanov, Zhur. obshchei Khitn., 1970, 40, lo

991 [ J . Gen. Chem. ( U . S . S , R . ) , 1970, 40, 9761. W. Haubold, D. Karnmel, and M. Becke-Goehring, 2. anorg. Chem., 1971, 380, 2 3 . V. N. Prons, M . P. Grinblatt, and A. L. Klebanskii, Zhur. obshchei K h i h . , 1970, 40, 589 [ J . Gen. Chem. ( U . S . S . R . ) ,1970, 40, 5591.

Organophosphorus Chemistry

190

Derivatives of the type, R2P.N=P(NH,)X1,, were obtained by displacement of the chlorine atoms marked with an asterisk by ammonia. The parent halides decomposed at ca. 150 "C giving, amongst other products, cyclophosphazenes, (NPR,),, and phosphazene polymers.

B. From Cyano-compounds and Phosphorus(v) Halides.---Continued reports of the reactions of alkyl cyanides with phosphorus pentachloride appear. With dicyanides12 the formation of phosphazenes occurs via a series of intermediates whose stability varies with the nature of X: X,C(CN )a

l'('1.5

+

X2C(CN)2,2PCI, >

[X,C(CN)CCI=N * PCI,] PC1,+

X,C(CN)CCI,N=PCI, (X = Me, Et, or Cl)

The second cyano-group reacts with PCI, at 150-160 e.g.

+ 3PC1,

3CI,C(CN)CCI,N=PCI,

?-

3PC13

t PCI,

"C:

+ 3CC13CCIa*N=PCI, + C,N,CI:,

Analogous reactions with tricyanides have also been reported :13 RR'C(CN)=CH(CN),

+ PCI,

RR'C(CN).C(CN)=CCI.N=PCI,, + HCI

( R and R1 include a variety of alkyl groups)

The latter products readily add chlorine at the olefinic linkage and are hydrolysed by aqueous sodium hydroxide to give ( 5 ) in good yield. RR'C-CCN I I1 ,CCl

HZN-C,

N

With 3-aminopropionitrile hydrochloride, phosphorus pentachloride produces l4 phosphazene linkages at both ends of the alkyl chain, as might be expected from the foregoing discussion : l2 l3

l4

P. P. Kornuta and V. 1. Shevchenko, Zhrrr. ohshchei Khitn., 1970, 40, 788 [ J . Goti. Chem. ( U . S . S . R . ) , 1970, 40, 7641. V. 1. Shevchcnko, N. R . Litovchenko, and V. P. Kukhar', Zhur. nbshchri Khitti., 1970, 40, 1229 [ J . Geti. Chrni. ( U . S . S . R . ) , 1970, 40, 12211. A . M . Pinchuk and 1. M . Kosinskaya, Zhrir. oh7hchei Khitti., 1970, 40. 546 [ J . GCII. Chenr. ( U . S . S . R . ) , 1970, 40, 51 21.

191

Phosphuzerres NC*CH,*CH,-NH,CI 80 "C

------+

+ 4PC1,

CI,P=N.CCI,.CCI,.CH,.N=PCI,-t 5HCl

Cl63If3

+ 2PCI3

The product is thermally unstable, however, and at 150-1800 "C in i w u o a molecule of phosphorus pentachloride is lost, leaving NC. CCI,. CH,. N=PCI3. With N-arylaminopropionitriles, the reaction is more complex and cyclic products, e.g. (6), are obtained :

(6)

+

NC.CH,CH,.NH,PhCl-

+ 4PC1,

----+

Compound (6) also decomposes at 160-170 HCI

(6)

+ PCI? f

5HC1

+ 21'CI, + (6)

"C:

PhN=CCl*CCI=CCI-N=PCI,

The products from the reactions with phosphorus pentachloride vary even with the nature of the aryl group. Thus, the p-chlorophenyl compound gave a product analogous to (6), but it was accompanied by the dimeric phosphazene, [p-CIC,H,NPCI,],.

C. From Azides and Phosphorus(Ir1) Compounds.-Typical

syntheses, which

generally proceed smoothly at 2 0 - 5 0 "C, include :15

+

Me,P(S)N, P(OR),X ----+ Me,P(S)-N=P(OR),X + N, (R = Et, X = OEt; R = Pr', X = OPr'; R = Pr", X = Me)

N-p-Vinylphenyl phosphazenes have also been obtained

by this route:

(X includes H, CN, C0,Et; Y includes CN, NO,, CO,H, CONH,, CO,Et, and CF,)

Their electronic spectra were reported to be similar to the spectra of NN-dimethyl-p-vinylanilines,Me,NC,H,-p-CH=CXY. Although azides l5

S. Z. Ivin, N. D. Shelakova, and V. K. Promonenkov, Zhiir. obshchei Khim., 1970, 40, 561 [ J . Gen. Chern. ( U . S . S . R . ) , 1970, 40, 5281. 1. N. Zhmurova, A . A. Tukhar', and A. V. Kirsanov, Zhrrr. obshchei Khittr. 1970, 40, 2154 [ J . Geti. Chem. (U.S.S.R.), 1970, 40, 21391.

192

Organophosphorus Chemistry

and phosphines generally form phosphazenes, hydrazoic acid gives azide salts :17 4HN3

+ Ph,P. C,H,-p-PPh,

------+ (H,N * PPh,. C,H,-p-PPh,NH,)2

2N3-

Only on reaction of this salt with sodamide in liquid ammonia is the expected diphosphazene obtained : (H,N. PPh,. C6H,-p-PPh,NH,)2+ 2N3- + 2NaNH, HN=PPh,-C,H,-p-PPh,=NH

+ 2NH3 + 2NaN3

Not surprisingly, this diphosphazene is a strong base (p& = 22.58, rf. Et,N = 18.35, both in MeNO,) and its basic properties are typical of those of Ph3P= N H . The addition products of hydrazoic acid and isocyanates have been used l 8 as intermediates in the synthesis of monophosphazenes: R,P(O)NCO

+

R = C1

OEt

OPh

OEt

R1 = Ph

Ph

Ph

OMe

HN,

R,P(O)*NH*CO.N,

OPr' OPhl

Phosphazenyl carbamates may also be obtained RO.CO.N,

+

20

MeP(OR1),

oc

l9

in a similar way:

RO.CO.N=P(OR'),Me

+ N,

(R and R1 include a variety of alkyl groups)

At higher temperatures ( 1 20-140

"C) the carbamates decompose:

.

R O C O N =P ( 0 Rl), Me

----+

R O - C O -NRIP(0)(OR1)Me

+

MeP(0)(OR1),

Numerous examples of C-phosphazenyl-s-triazines continue to be synthesised because of interest in their physiological properties. Most of these have been obtained by the azide route: (7)

+ R,P

(8)

+

N,

X includes NHAlkyl and NHAryl substituents

\

(ref. 20)

R, = Ph,, (AlkO),, or (Et,N),(EtO)

2o

A. S. Shtepanek, E. N. Tkachenko, and A . V. Kirsanov, Zhirr. obshrhei Khinr., 1970, 40, 1677 [J. Gen. Chem. ( U . S . S . R . ) , 1970, 40, 16651. L. I. Samarai, 0. I . Kolodyazhnyi, 0. V. Vishnevskii, and G . I. Derkach, Zhrtr. obshchei Khim., 1970, 40,750 [ J . Gen. Chern. ( U . S . S . R . ) , 1970, 40, 7261. V. A. Shokol, L. I. Molyarko, and G . I. Derkach, Zhur. obshchei Khim., 1970, 40, 998 [J. Gen. Chem. ( U . S . S . R . ) , 1970, 40, 9831. M. I . Bukovskii, S. N. Solodushenkov, A. I . Mosiichuk, and V. P. Kukhar', Zhrrr. obshchei Khim., 1970, 40, 782 [J. Gen. Chenr. (U.S.S.R.), 1970, 40, 7581.

Pliosphozcnrs

193

X includes OAlkyl, OAryl, NH,, and NHEt

\

N=PR, I

y 3

&" II

I

(ref. 21)

I

R includes Ph, OPh, and Alkyl

I

/ c ,N , qX S

II

s /C+N/C\

( 7)

X

(8)

Typically, the phosphazenyl groups in these derivatives may be hydrolysed to phosphoramides: -N= P(OA1k),

-

1120-11

'+

-NH*P(O)(OAIk),

+ AlkOH

When the phosphazene produced by the decomposition of an azide contains an N-phosphoryl group with an alkoxy-substituent, isomerization may occur on heating. Examples of such phosphazenes were produced:22

+

XCH,P(O)(OR)N,

i

R1R2,P ----+

XCH,P(O)(OR)N= PR1R2,

+

R includes Et and P h ; R1 includes OMe, OEt, OPr', Me, Ph, and NMe, R2 includes OMe, OEt, OPr', Ph, and NMe,

N,

1

To show that these phosphazenes had not isomerized (in the way shown below), the following series of reactions was carried out: Me(EtO),P(O).N,

+ (EtO),P

20 o c

---+

Me(EtO),P(O).N=P(OEt),

I

+ N,

165--175O('

Me(EtO)P(O). NEt * P(O)(OEt),

Me(EtO)P(O). NHEt

+ (EtO),P(O)CI + Et,N

The phosphoramide, Me(EtO)P(O). NEt P(O)(OEt),, independently synthesised by the route shown, was obtained only on heating the phosphazene at 165-175 "C for several hours. 31P N.m.r. and i.r. spectroscopy confirmed these findings and were used to show that the formation of XCH,P(O)(OR). N=PR1R2, was never accompanied by isomerization. el

24

V. P. Kukhar', M. I. Bukovskii, T. N. Kasheva, V. S. Paleichuk, A. A. Petrachenko, and S . N. Solodushenkov, Zhur. obshchei Khim., 1970, 40, 1226 [J. Gen. Chem. (U.S.S.R.), 1970,40, 12171. V. A. Shokol, G . A. Golik, V. T. Tsyba, Yu. P. Egorov, and G. I. Derkach, Zhur. obshchei Khim.,1970, 40,1680 [ J . Cen. Cheni. (U.S.S.R.),1970,40,16681.

Organophosphorus Chemistry

194

Potentiometric titration methods have been used to study the tautonierism of certain arylaininophosphazenes produced by the azide route :23

a The position of the equilibrium could be correlated with the Hammett a-constants of the substituents X and Y . D. Other Methods.-Last

year it was shown that the equilibrium:

7R2P(H)=N.Y

R,P*NHY

lies to the right only when electron-supplying substituents are bonded to phosphorus and electron-withdrawing substituents are bonded to nitrogen. Further examples of phosphazenes confirming these generalizations have since been synthesised:24 R,PCI

+ HNY

R = Me

a Me

R,P(H)=N*Y Me

Y = S02CF3 SO,C,H,Me

PS(QPh), Ph SQ,CF,

I

Using R = Ph, Y = S0,C,H4Me or PS(OPh),, the aminophosphine form was detected. A second mole of chlorophosphine was added and in all cases P-phosphinophosphazenes were obtained : R,P(H)=N.Y (or R,P.NHY)

+ R,PCI + GHY

R2(R,P)P=N-Y

There was no evidence for the alternative diphosphinoamines, R,P-N(Y)PR2, in the 31Pn.m.r. spectra, which revealed relatively large P-P spin-spin coupling constants (225-300 Hz), characteristic of directly-bonded phosphorus atoms. It is interesting to note that the two groups of compounds gave different types of sulphide on reaction with sulphur : R,P(H)=N,Y (or R,P-NHY) R,(R,P)P=N*Y

+ $3,

+ +S8

-----+

-----+ R,P(S).NHY

R,(R,PS)P=NY

Apparently, the second product did not react further with sulphur, by a reaction which might be possible if any R2P-NY-R2PS were present. 23 24

M. I. Kabachnik, V. A. Gilyarov, B. A. Korolev, and T. A. Raevskaya, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 772 (Chem. Abs., 1970, 73, 35 449n). A. Schmidpeter and H. Rossnecht, Z . Naturforsch., 1971, 26b, 81.

Phosplinzeries

195

I n view of the above findings, it is not surprising that no evidence was obtained for the presence of a phosphazene in aminodifluorophosphine, which was recently obtained by the reactions: PF2X

+ ZNH,

+ PF2NH2 + NH,X

~

(X = (21%or Br25~2s)

The reactions of boron trifluoride adducts of ammonia,27and priniary,z8 ~ e c o n d a r y and , ~ ~ tertiary amines 29 with phosphorus pentachloride have been studied and in the first two cases acyclic phosphazenes were obtained. With the ammonia-adduct, a previously characterized phosphazene salt was obtained:27 BF3.NH3

+ 3PC1,

[C13P=N*PC131tBC14-

+ 3HCl + PF,CI,

Analogies between this reaction and the initial stages of the reaction between ammonia and phosphorus pentachloride were drawn, where one of the initial products may be the adduct [H3N.PCl,]+. Reaction of [CI,=N. PC13]+BCI,- with sulphur dioxide gave products of uncertain identity in spite of the fact that [CI,P=N.PCl,]+PCI,- gives CI,P=N.POCI, under the same conditions. The 31P n.m.r. spectra of these products (from the BCl,- salt) suggest that (9) and (10) may be

-BC13 (9) present. I n order to shed more light on these findings, the reactions of CI,P=N.POCl, with BCI,, BF,, and PF, were followed by 31P n.m.r. With BCI, two products were obtained one of which was identical to one of the compounds (9) or (10). However, the spectra were relatively simple in the cases of BF, and PF,, and the products were formulated: CI,P=N.kl,-O-%

(X = BF, or PF,)

The reaction between [CI,P=N- PCI,] +BC14-and hydrogen sulphide was also straightforward : [CI,P=N.PC13]+BC14-

+ H2S

----+

C13P=N*PSC12

+ 2HC1 + BCIB

The methylamine adduct of boron trifluoride and phosphorus pentachloride gives 28 a zwitterionic product (1 1) which may also be formulated as a monophosphazene (12): F,B,NH,Me z6

28 27 28 %@

+ ZPCI,

---+

( 1 1)

e(12) + PCI,F,

J. E. Smith and K. Cohn, J . Amer. Chem. Soc., 1970, 92, 6185. D. W. H. Rankin, J . Chem. Soc. ( A ) , 1971, 783. H. Binder and E. Fluck, Z . anorg. Chern., 1971, 381, 21. H. Binder and E. Fluck, Z . nnorg. Chem., 1971, 381, 116. H . Bindcr and E. Fluck, 2. anorg. Chem., 1971, 381, 123.

+ 2HCI

196

Organophosphorus Chemistry

Coinpound (1 1) undergoes an interesting series of reactions which are summarized below: (I I) (11)

(11)

+ 2PCI5 + 2C6H5N + H,S

+ PCI,+BCI,+ 2C5H,N,BC13 MeNHP(S)CI, + BCl,

--+

(MeNPCI,),

----+

(MeNPCl,),

----+

With one mole of phosphorus pentachloride, MeNH,,BF, gives a series of mixed halides (13) of which only one (n = I ) was isolated, In each halide the fluorine atoms were shown to be bonded to boron by the appearance of llB-lQFand absence of 31P-1QFspin-spin coupling. An analogous N-phenyl compound (14) was obtained from PhNH,,BF3 and phosphorus penta-

+ /

MeN,(n

=

+

pc13

/

PhN,-

BCI,-,F, I , 2, o r 3 ) (13)

PCI3 BCI,

(14)

chloride. I n this case the more weakly basic nitrogen atom could be displaced by diethyl ether, leaving a dimeric monophosphazene: 2(14)

+ 2Et20

> 2CI,B,OEt,

-

+ (PhNPCIJ2

Further examples of tribromophosphazenyl derivatives, which are not available from the Kirsanov reaction, have been reported :,O RS0,NSO

+ PBr,

RSO,N=PBr,

+ SOBr,

(R = Me, CF,, Ph, Me-p-C,H,, or C1-p-C6Hp)

These derivatives undergo ready reactions with silylamines : RSO,.N=PBr,

+ Me,SiNR1R2

----+

Ph CF, Me H

p-Me-C,H,

R1 = Me R2 = Me

Me SiMe,

SiMe,

R = Me

H

RS0,N=PBr,NR1R2

1

+ Me,SiBr

A series of methylenaminophosphines, R2P.N= CR',, has been obtained 31 by condensation of a chlorophosphine, R,PCI, with an imine, s1

H. W. Roesky and G . Remmers, Z . Nutitrforsch., 1971, 26b, 75. A. Schmidpeter and W. Weiss, Chenz. Ber., 1971, 104, 1199.

Phosphazenes

197

HN=CR12, in the presence of triethylamine. When at least one of the R1 groups is alkoxy, these phosphines may be converted into monophosphazenes by a quaternization and subsequent pyrolysis: e.g. Ph,P-N=CR(OMe)

+ Me1

-

+

Ph,MeP.N=CR(OMe) I-

1

(R = Ph or OEt)

lieat

+ Me1

Ph,MeP=N.CO.R

These N-acyl phosphazenes also decompose further on heating to Ph,MePO and RCN. The elimination of methyl iodide probably occurs by a course closely related to the elimination of alkyl halides in the Arbusov reaction, where the alkoxy-group undergoes nucleophilic attack by halide ion. Another new route 32 to monophosphazenes (1 6 ) involves the reaction of N-(phenylsulphony1)phosphinous amide with benzaldehyde : Ph,PNHSO,Ph

+ PhCHO

------+

-

Ph 1 Ph.,P-CH.OH

Ph

+

[(15)]

I

PhDP-CH-0-

II

I H N -S0,Ph

N.SO,Ph

(15)

(16)

(16)

1120

(17)

Ph

I

Ph P C

II

Ha

0H

0 (17)

This reaction may be visualized as proceeding by nucleophilic attack of tervalent phosphorus at the carbonyl group to give an intermediate such as (1 5 ) . The structure of (1 6 ) was deduced from the fact that it was hydrolysed to the known phosphine oxide (1 7). Methylenephosphoranes (phosphorus ylides) may also be converted into monophosphazenes by reaction 33 with benzonitrile : Ph3P=CHPh

+ PhCN

------+

Ph,P=N-CPh=CHPh (mixture of two geometrical isomers)

A mechanism for this reaction involving nucleophilic attack of the ylide on the cyanide group and formation of the P=N linkage via a four-centred intermediate was formulated. The structure of this phosphazene was confirmed by its synthesis from the vinyl azide, Ph(N,)C=CHPh, and triphenylphosphine. Phosphoranes stabilized by electron-withdrawing

33

A. N. Pudovick, E. S. Batyeva, and V. D. Nesterenko, Zhur. obshchei Khim., 1970, 40, 502 [ J . Gen. Chem. (U.S.S.R.), 1970, 40, 4681. E. Ciganek, J . Org. Cherrl., 1970, 35, 3631.

198

Organophosphortrs Chemistry

substituents, R, on the P=CR2 group were unreactive to benzonitrile, but the more electrophilic nitriles cyanogen and trifluoroacetonitrile readily gave phosphazenes in high yield :

+ NC-CN Ph,P=N.N=CPh, + CF3CN Ph,P=CHCN

Ph,P=N-C(CN)=CHCN Ph,P=N.CCF,=N.

N=CPh,

Phosphazenes were also obtained from phosphoranes, Ph,P= CR,, with a wide range of R substituents including H, Me, CO,Me, COPh, p-fluorenyl, and CO,(CH,),CO,-. An unusual group of phosphazenes, said to be useful as fabric softeners, has been obtained 34 from various dichlorophosphoranes and N-lithiated sulphur imides : RMe2PCl,

+

R = C,,-C,,

R'MeS(O)=NLi

+ -----+ [RMe,P=N=S(O)MeRl] C1-

+ LiCl

alkyl

R1 = Me or C16H33 3 Properties of Acyclic Phosphazenes A. Halogeno-derivatives.-Interest in the reactivity of trichlorophosphazenyl derivatives, RN= PCl,, which may exist as monomers or cyclic dimers, has been sustained. Previous findings on the reactivity of the dimers (1 8) to sulphur dioxide in polar solvents have been c ~ n f i r m e d and ,~~ it is found that the cyclic dioxides (19) formed are readily cleaved by R I

(R = Me, Ph, p-Me-C,H,, or p-Cl-C,H4)

hydrogen chloride to give open-chain phosphoramides. Monomeric phosphazenes, Cl,P=NR, with more electron-withdrawing nitrogen substituents (R = RlCOArSO,, p-o2NC6H4,2,6-C12C6H3,or RlCCl,. CCl,) do not react with sulphur dioxide and hydrogen chloride 34 T.J. Logan and T. W. Rave, U.S.P., 3 524 881 (Chem. A h . , 1970, 7 3 , 88 016a). 36

V. P. Kukhar', Zhur. obshchei Khim., 1970, 40, 785 [J. Gen. Chem. (U.S.S.R.), 1970, 40,7611.

Phosphazeiies

199

under similar conditions. It may be noted that the enthalpy of formation of the dimer shown above [( l8), R = Me] has been determined 36 by combustion calorimetry leading to P-N bond energies of 69 and 77.5 kcal mol-l for axial and equatorial P-N bonds respectively (in the phosphorus trigonalbipyramid). This may be with P-N bond energies of 79 and 69 kcal mol-1 for [PhNHP(O)NPh], and P,(NMe), (tervalent P) respectively. N-(Phosphinothioy1)phosphazenes have recently been employed 37 as precursors of novel compounds containing the P-N-P skeleton : XX'P(S)-N=PF,Cl

+ HC0,H ----+

XXIP(S)*NH.P(0)F, + CO

+ HCI

(X = X' = F; X = F, X' = C1; X = X' = C1)

I.r,, n.m.r., and mass spectroscopy showed that the N-H bonded compound was present, rather than its isomers, e.g. F2P(S).N=PF20H or HS. F,P=N. POF,. The N-deuteriated analogues, XXlP(S). ND. POF,, were obtained by solvolysis with deuteriated formic acid. Reactions of the same halogenophosphazenes with ammonia were also described, in which halide-ion displacement took place at the phosphazenyl group rather than at the thiophosphoryl group : XX'P(S).N=PF,CI

+ 2NH3

XX'P(S)*N=PF,NH,

+ NH,CI

In one of the ammonolysis products, halide ion exchange occurred: 2FCIP(S) - N=PF,NH, F,P(S)-N=PF,NH,

+ CI,PS-N=PF2NH2

A related form of isomerization to that described above has been studied 3* in the case of the esters (20) C13P=N*POC12

11ONa

(20)

R = Bun, Bd, Hex", Oct", C,H40C2H6,C,H,CI, CH(CH,Cl), CH,CH,CF,, or C2H4F

1

Compound (20) may be converted into (RO),P(O)NHP(O)(OR), by reaction with hydrogen chloride, and these same compounds may be obtained from C13P=N. POCl,, ROH, and triethylamine. These results indicated that an equilibrium of the type:

s8 s7

3n

H. FIeig and M. Becke-Goehring, 2. anorg. Chem., 1970, 376, 215. H. W. Roesky and L. F. Grimm, Chem. Ber., 1970, 103, 3114. V. V. Kireev, G . S. Kolesnikov, and S. S. Titov, Zhur. obschei Khim., 1970, 40, 2015 [ J . Gm. Chem. (U.S.S.R.),1970, 40, 20021.

200 OR

/

(RO),P=N.P=O \ OR

\I1 I ,P-N-P,

OH 0 I II -p=N-p-

/I,

1

I

obtains for these esters, and that it lies well to the left in acidic or basic solution, as shown by spectroscopic methods. The reactions of the esters, (RO),P(O)- NH. P(O)(OR),, with chlorosilanes have also been followed.3* As was found in the hexakisalkoxycyclotriphosphazatrienes, one of the P--0-C links is replaced by a P-0-Si link : (RO),P(O). NH * P(O)(OR), ----+

+ Ph3SiC1 (RO),P(O).NH*P(O)(OR)(OSiPh,)

+ RCI

(R includes various alkyl groups)

However, in no case was any evidence obtained that isomerization to a phosphazene had occurred. Alcoholysis of the diphosphazene, CI,P=N. PCl,=N.POCI,, was also effected 40 by alcohols in the presence of triethylamine, but in this case i.r. spectroscopy indicated that both isomers were present :

-

HO * P(OR),= N P(OR),= N * P(O)(O R), O=P(OR),.NH*P(OR),=N.P(O)(OR), ~

(R = Bun, C,H,OC,H,, or C2H4CI)

Reactions of these mixtures with triphenylchlorosilane, leading to the formation of one P*0.SiPh3 group per molecule, probably takes place at a terminal phosphorus atom. An alkyl-group migration has been observed 41 in some N-sulphonylphosphazenes : XS0,*N=PC13

+ ROH

--

X.SO,*N=PCI,*OR

+ HCI

I

distil

XSO,. N R . P(0)Cl2

A parallel may be drawn between this rearrangement and that observed in Me(EtO),P(O)- N=P(OEt), (Section 2). The intermediate alkoxyphos-

41

V. V. Kireev, G . S. Kolesnikov, and S. S. Titov, Zhur. obshchei Khirn., 1970, 40, 2634 [ J . Gen. Chem. ( U . S . S . R . ) , 1970, 40, 26271. A, A. Volodin, V. V. Kireev, G. S. Kolesnikov, and S. S. Titov, Zhur. obshchei Khim., 1970, 40, 2202 [ J . Geit. Chern. (U.S.S.R.), 1970, 40,21891. H . W. Rocsky and W. Grosse-Bijwing, Atigew. Chein. Internat. Edn., 1971, 10, 344,

20 1

Phosphnzenes

phazenes were identified by n.m.r., but rearranged on distillation. A dimethylamino-derivative, FSO,. NMeP(0)CIN Me,, of one of the rearrangement products was obtained by reaction with Me,Si -NMe,. N-Sulphonylphosphazenes may also be converted 4 2 into phosphazanes in the presence of certain protic acids: CF,S0,*N=PC13 FSO, N=PCI,

+ HC0,H

+ CF,S03H

CF,SO,*NH-POCl, + HCI

+ CO

FS02*NH-P(0)C12+ O(S02CF3)2+ HCI

With fluoro- or chloro-sulphonic acids the P=N linkage is replaced4? by an S-N bond: CF,SO,*N=PCI,

+ XSO3H

A

CF,S02.NH.S02X

+

POCI,

(X = F or CI)

This same class of compound undergoes 43 ready reaction with silylaniines at the phosphorus atom rather than at the sulphur atom:

-

CISO, N = PCI,

+ (Me,Si),N Me _I__,

CISO,.N=PCI,.NMe-SiMe,

+ Me,SiCl

Subsequent reactions with phosphorus pentachloride and with its monophenyl derivative lead to the dimer (C1,PN Me), and N-sulphonylphosphazenes : 2CISO2.N=PCI,.NMe.SiMe, + 2XPC1, ----+ 2C1S0,.N=PC12X (CI,PNMe),

+

+ 2Me,SiC1

(X = C1 or Ph)

The 35CC1n.q.r. spectra of CISO,.N=PCI, have been followed44over a range of temperatures, thus enabling barriers to rotation about S-N and P-N bonds to be calculated as 0.940 and 6.3 kcal mol-1 respectively. Many typical reactions of chlorophosphazenes, R ( C 0 . N=PCI,), [R = -CCI2- or -CCI,(CH2)5CCI,-] with nucleophiles have been reported :45

+

R(CO*N=PX,), + 6HCI R(CO.N=PCI,), 6XH (X = OC,H,-p-N02, NHC,H,-ni-Me, NHCH,Ph, or NHC,H,-p-OMe) As expected, reactions with anhydrous formic or acetic acid in benzene

-

gave 4 6 a series of phosphoramides, R(CO*N H POCI,),. I2 43

p6

H. W. Roesky and H . H . Giere, Inorg. N i d e o r Chem. Letters, 1971, 7, 171. U. Bieller and M. Becke-Goehring, Z . onorg. Chern., 1971, 381, 209. R. M. Hart and M . A . Whitehead, M o f . Phys., 1970, 19, 383. V. P. Rudavskii, N. A. Litoshenko, and V. P. Kukhar', Zhur. obshchei Khim., 1970, 40, 1002 [ J . Gen. Chem. ( U . S . S . R . ) , 1970, 40,9871. V. P. Rudavskii and N. A . Litoshenko, Khim. Prom., 1970, 24 (Chem. A h . , 1971, 74, 52 965s).

Organophosphorils Chemistry

202

N-Chloroalkylphosphazenes generally undergo preferential chlorine atom replacement at phosphorus with alcohols and amines. However, it has now been shown4' that the weakly basic arylsulphonamides may preferentially attack the a-dichloromethylene group : CCl,.CCI,.N=PCI,

+ NH,SO,Ar 120-1343 "C -

I _ _ _

f

ArS02.N=C(CCI,)N=PCI,

+ 2HCI

(Ar = Ph or substituted phenyl group)

The products are monomeric in benzene and are characteristically hydrolysed at the phosphazene grouping: -N=PCI3

11.0

-NH.POCI,

Indirect confirmation of the structures of these products is provided by the fact that arylsulphonarnides do not react with phosphazenes, R.N=PCI,, where R does not contain an a-dichloromethylene group. During attempts to esterify chloroalkylbiphosphazenes, reaction took place at dichloromethylene and phosphazene groups, but their relative reactivity was not determined :4* (CH,),(CCI,CCI,N=PCI,),

+ 8AlkOH

(CH,~.[CCI,-C(OAlk),=N~P(O)(OAlk),],(n = 2, 4, 5 , or 6) Several examples have already been noted where the phosphazene group rearranges to the energetically more favourable phosphoryl group. Since chlorine dioxide effects such a change in N3P,C&, the effect of chlorine dioxide on monophosphazenes has now been investigated :4a ArS0,-N=PCI,

+ CI,O

-

C1,

+ ArCI,NO,PS

I t seems likely that the latter product may have the structure,

-

A rS(0)(OCI)= N POCI, (Ar = Ph, C,H,-p-Me, C,H,-p-CI, or C,H,-m-NO,)

The infrared spectra of N-chloroalkylphosphazenes, Cl,C. N= PCI3, CCI,. CCI,. N=PC13, and (CI,C),CCI* N=PCl,, have been studied.60 These spectra suggest an increase in the C-N-P bond angle in the above 47

4u

40

V. P. Kukhar', V. Ya. Semenii, and N. P. Pisanenko, Zhur. obshchei Khirn., 1970, 40, 557 [ J . Gen. Chem. (U.S.S.R.), 1970, 40, 5241. V. P. Kukhar' and A. A. Koval', Zhirr. obshchei Khim., 1970, 40, 776 [ J . Gen. Chem. (U.S.S.R.), 1970, 40, 7531. P. P. Kornuta and V. I. Shevchenko, Zhur. obshchei Khirn., 1970, 40, 551 [ J . Gen. Chem. (U.S.S.R.), 1970, 40, 5171. D. P. Khomenko, G. G . Dyadyusha, and E. S. Kozlov, Z h w . stnrkt. Khim., 1970, 1 I , 660 (Chem. A h . , 1971, 74, 8002a).

Phosphazenes

203

order, mainly as a result of steric effects. Normal co-ordinate calculations 51 on the compounds, CF,. CCI,. N=PC13, (CF,),CCl. N=PC13, and (CCl,),C. N= PCl,, show that the out-of-phase P-N-C stretching mode, at 1400--1500cm-* in the i.r. spectrum, may be related to changes in the P-N-C bond angle. Fluorination 5 2 of C13P.NMe- BCI, (Section 2) by arsenic trifluoride results in the formation the well-characterized dimeric phosphazene (23) : +

C136.NMe.kJ ,

+ 2AsF,

--+

[F,i!-NMe.EF,]

+ 2AsC1,

B. Aryl Derivatives.-The Ph,P=N group imparts high nucleophilic reactivity to the tervalent phosphorus atom in N-(dipheny1phosphino)triphenylphosphazene, Ph,P=N. PPh,. Ready reactions occur 63 with methyl iodide, phosphorus(rr1) halides, and bromine : Ph,P=N

*

PPhz

I

+ RX

R = Me PhzP Ph,P

X = I

Cl

Br

[PhaP:

’-

N Z PPhZR] X

1

PhPCI

Br

C1

Br

With phosphorus trichloride, a rather complex reaction results partly in the formation of [ P h , P ~ N z P P h , .PPhCI] +C1-. The reactivity of the phosphorus(ir1) atom is also demonstrated by its ability to desulphurize thiophosphoryl chloride, and its ready reactions with Group VI elements, diborane, and carbon disulphide: Ph,P=N.PPh,

+

PSCI,

__c_,Ph,P=N*P(S)C12

+ PCI,

(X = 0, S, Se, Te, or BH,) D. P. Khomenko, E. S. Kozlov, and G. G. Dyadyusha, Specrroscopy Letters, 1970, 3, 120. H . Binder and E. Fluck, Z . attorg. Chent., 1971, 382, 240. H . G . Mardersteig and H . Niith, Z . onorg. Chmt., 1970, 375, 272.

204

Organophosphorus Chemistry

+-

With carbon disulphide a betaine-type structure Ph,PzNIrrPPh,-C(S)S, may be formulated for the reaction products. The 31P n.m.r. spectra of these compounds were discussed in detail. The reactions of triphenylphosphazenyl derivatives with many other electrophilic species have been described. With sulphur tetrafluoride, sulphur imines are formed,64 possibly via the four-centred intermediate (24) : Ph,P-NR

[

Ph3P=N*R

+ SF4

-

Ti,,] (24)

[(24)]

Ph3PF2

+ F,S=N*R

(R = H, Et, Ph, or SiMq)

With cobalt(1r) chloride, complexes of the monophosphazene, Ph,P=NH (= L), of stoicheiometry CoCI,L,TH F and CoCl,L, have been

Their i.r. and U.V. spectra were compared with analogous complexes of triphenylphosphine oxide. The scope of the reactions of phosphazenes with alkyl halides and, subsequently, water, as a preparative route to secondary amines (as their hydrohalides) has been investigated :5e Ph,P=N*R

-

+ R'X

[Ph,P-NRR']+Xxr20

>

Ph,PO

+ + H,NRRIX-

R = Me, Et, Pr", Bun, But, or 1-adamantyl; R1 = Me or Et; X = CI, Br, or I

-

This route was limited to R1 = Me or Et, since the use of higher alkyl groups resulted in HX elimination and olefin formation : Ph,P=N.R

+ R'X

[Ph,P.NHR']+ X(R' = Pr and higher alkyl)

Mono(tripheny1)phosphazenes readily C-bromoimides :57 Ph,P=N.R +R'N=C,

/

Br

displace

+ olefin

bromide

--+(25)

ion

from

(26)

R

(R O4

65

*'

=

Me, R'

=

Ph; R

=

Pri, R1

.=

Ph)

R. Appel and E. Lassmann, 2. Naturforsch., 1971, 26b,73. K . B. Yatsimirskii, Z . A. Sheka, and E. I. Sinyavskaya, Zhur. neorg. Khirn., 1970, 15, 1552 (Russ. J . Inorg. Chem., 1970, 15, 796). H . Zimmer, M. Jayawant, and P. Gutsch, J . Org. Chern., 1970, 35, 2826. T. Winkler, W. von Philipsborn, J. Stroh, W. Silhan, and E. Zbiral, Chem. Comm., 1970. 1645.

Phosphareries

205

The lH n.m.r. spectra of (25) and (26) are interesting in that exchange of the triphenylphosphonium moiety between the non-equivalent nitrogen atoms is slow on the n.m.r. time scale at ca. - 60 "Cand fast at ca. 60 "C. N-Imidophosphazenes readily undergo reactions 5 8 with acid halides in the presence of triethylamine:

+

RC(=NH).N=PPh,

+ XCI

Et3N ~

RC(=NX)*N=PPh,

+

R includes CCI,, CF,, and CH,CCI, X includes SO,Ph, COPh, COMe, CO,Me, SOC,H,-p-NO,

SC, H,-p-NO,, and P( 0)(0Ph),

+

HCI

I

Generally, these derivatives were stable in air, but the acetyl and benzoyl derivatives were readily hydrolysed at the imide rather than at the phosphazene linkage:

-

R C( =N * CO R1) N =PPh,

1120

>

RCO*N=PPh3

+ H,N.COR1

The imide nitrogen atom was also most reactive to a variety of electrophilic species (hydrogen halides, pseudohalogens, and alkyl halides) in the parent N-imidophosphazenes, R(C=NH)- N= PPh,. With t-butyl hypochlorite the N-chloro-derivatives, R(C=NCI). N= PPh,, were obtained. N-p-Vinylphenylphosphazenes have been prepared by condensation of aldehydes with active methylene compounds: Ph,P=N+C,H,-p-CHO

+ CH2XY

These were also obtained by the azide route, which proved to be more versatile : Ph,P

+ N,C,Hd-p-CH=CXY

Ph,P=N.Cp,Hd-p-CH=CXY

+

N,

(X and Y include H, CO,H, CO,Et, NO,, CN, and CF,) sR Kn

A. S. Shtepanek, E. N. Tkachenko, and A. V. Kirsanov, Zhur. obshchei Khim., 1970, 40, 766 [ J . Gen. Chem. ( U . S . S . R . ) , 1970, 40, 7421. I . N. Zhmurova, A. A . Tukhar, and A . V. Kirsanov, Zhur. obshchei Khitrt.. 1970, 40, 2154 [ J . Gen. Chern. ( U . S . S . R . ) , 1970, 40, 21391.

206

Orgonophosphorus Chemistry

t-Butylperoxyphosphazenes have been obtained 6o in good yield by simple nucleophilic displacement reactions : ArSO,N=PPhCI,

+ 2Na0,But 8-- 10 "C1

ArSO,N=PPh(O,But),

+ 2NaCI

(Ar = Ph, C,H,-p-CI, C,H,-p-Me, or C,H,-p-NO,)

These peroxides have also been described 61 in a recent patent application. In attempts to synthesise compounds with alternating phosphazene linkages, an unusual preference for the formation of a triphosphazene became apparent :62 Ph,P(O)- N=PPh,CI

NIT3

>

Ph,P(O).N=PPh,*NH,

PhzPC13

(27)

A similar result had previously been observed using the azide synthesis, and the unusual stability of these triphosphazenes has now been rationalized in terms of conversion of (27) into the relatively stable cyclic product (28). Evidence for the structure (28) was deduced from its 31P n.m.r. spectrum

and from the fact that the chloride ion was readily replaced by other large anions, e.g. BPh4-, Clod-, SbF6-, without significant changes in the i.r. or n.m.r. spectra. Ammonia, methylamine, and dimethylamine effect ring cleavage to give derivatives, Ph2P(0)(.N=PPh2)3NRR1 (R = R1 = H; R = H, R1 = Me; R = R1 = Me), Compound (28) was most readily prepared : Ph,P(O)*N=PPh,.NH,

+ CIPPh,=N.PPh,CI

(28)

+ 2HC1

The dipole moments, u.v., and lH n.m.r. spectra of a series of N-sulphonyl-P-aryl-phosphazenes (29) (X = H, Cl, OMe, NMe,, Br, COMe, or

6o

u2

T. I . Yurzhenko and A. G . Babyak, Zhrtr. ohshchei Khim., 1970,40, 1662 [ J . Gen. Cheni. ( U . S . S . R . ) , 1970, 40, 16511. T. 1. Yurzhenko and A. G . Babyak, U.S.S.R.P., 271 519 (Chetn. A h . , 1970, 73, 120 757f). A. Schmidpeter-and K. Stoll, Angeir.. Cheni. Internat. Edn., 1971, 10, 131.

Pitosphazenes

207

NO,) have been reported.63 The basicities of triphenylphosphazenes, Ph3P=N.C6H4X, with a wide range of rnetn- and para-substituents X, have been determined 64 in alcohol and in nitromethane. An interesting feature of these measurements was that when X = m-N=PPh,, the pK, was higher than when X = rn-NMe,, but the pK, when X = p-N=PPh3 was lower than when X = p-NMe,. In related work the auxochroniic action of the Ph,P=N group was further explored.65 In compounds of the type Ph,P=N. C6H4-p-CH=CH. R (R = various heterocyclic groups) the phosphazene linkage was produced by the azide method. The electronic spectra of these derivatives were described.

C. Other Derivatives.- An extensive compilation of the 31P chemical shifts of compounds (mainly linear and cyclic phosphazenes), where phosphorus is surrounded by four nitrogen atoms, has appeared.66 These shifts have been correlated with expected states of nitrogen hybridization. For example, increasing s-character in the nitrogen hybrid orbitals, as in a change P-N --f P=N, generally results in an upfield 31Pshift. The 31P shift also appears to be linearly related to the degree of substitution when ami no-groups are replaced by phosphazenyl groups. The kinetics of the alkyl-halide-promoted phosphazene phosphoramide rearrangement : --f

A \ B--P=N--Ph /

A

+ AlkX

Alk

\

/

+ II-P-N-Ph // 0

OAlk

+ AlkX

have been followed.67 Rate measurements were made using the intensity of the band in the i.r. spectrum associated with the P=O stretch. The pure phosphazenes were obtained by the azide route: AB(Et0)P

20 o c

+ N,Ph

A = EtO

Ph

Me

Et

B = EtO

EtO

EtO

EtO

AB(EtO)P=N*Ph

Ph

+ N,

Et

The rearrangement follows first-order (in the phosphazene) kinetics and the rate increases as the electron density supplied by the substituents A and B increases. It was suggested that the reaction proceeds via a sixmembered transition state such as (30). O3 64

H. Goetz and J. Schmidt, Tetrahedron Letters, 1971, 23, 2089. V. P. Kukhar’, A. A. Petrashenko, 1. N. Zhmurova, A. A. Tukhar’. and S. N. Solodushenkov, Zhur. obshchei Khim., 1970, 40, 1696 [J. Gen. Chem. (U.S.S.R.), 1970, 40, 16821.

65

66

67

1. N. Zhmurova, R. 1. Yurcenko, and A . V. Kirsanov, Zhur. ohshchei Khirn., 1970, 40, 982 [ J . Cen. Chem. (U.S.S.R.),1970, 40,9671. A. Schmidpeter and K. Schumann, Z. Nnturforsch., 1970, 25b, 1364. G. K. Genkina, V. A. Gilyarov, E. I. Matrosov, and M. I. Kabachnik, Zlirrr. ohshdwi Khini., 1970, 40, 1496 [J. Geti. Chent. (U.S.S.R.), 1970, 40, 14821.

208 (RO),P=N.Ph

+

-

Organophosphorus Chemistry

R'Y

(RO),P(O)*NRlPh

[(30)1

+ RY

Mention has already been made of the aminophosphine -j phosphazene rearrangement (Section 2). It has been noted that some of these phosphazenes, (31) and (32) [Y = S02.CF3, SOz-C6H4-p-Me, P(O)Ph,, P(S)Ph2, or PS(OPh),], exhibit 68 significant differences in the magnitude

of P-H coupling constants. For the derivatives (3 1) Jp-lI was in the range 564--606 Hz, and in (32) the range was 599-641 Hz, where phosphorus is part of a strained ring system. These differences in coupling constants were suggested to be related to changes in the state of hybridization at phosphorus. Interesting cyclic ionic species are obtained from the reactions of di(phosphazeny1)silanes with silicon halides at room temperature :

+

R,P=N-SiMe,.N=PR, (R

=

Me,SiX,

-

(33)

Me, X = CI; R = Me, X = Br; R = Me, X = 1)

The same products were obtained from the reactions of certain N-silylmonophosphazenes with organosilicon dihalides: ZR,P=N.SiMe,

(R = Me, X

+ 2Me,SiX,

= CI, Br, or

-----+

(33)

+ 2Me,SiX

I ; R = Et, X = Br or I ; R = Bun, X = Br o r I ) It

Me,Si,

/N\

,SiMe,

2X-

N I1

PR,

(33)

However, the following monophosphazenes and silicon halides underwent straightforward exchange reactions :'O O8

OD

io

A. Schmidpeter, H. Rossnecht, and K . Schumann, Z . Naturforsch., 1970, 25b, 1 182. W. Wolfsberger and H. Schmidbaur, J . Organometallic Chem., 1971, 28, 301. W. Wolfsberger, H . H . Pickel, and H . Schmidbaur, J . Organometallic Chem., 1971, 28, 307.

Phosphazenes

209

+

R,P=N-SiMe,

n = 1 X = CI

R',SiX,._,

-___

+ R,P=N-SiR',X,_,

Et

Bu"

Ph

Ph

Ph

-

Me Et

Me

0

0

1

2

Me 2

Me 2

Me 2

Me 2

CI

Br

CI

CI

C1

CI

Br

I

R = Me Me R'= Me -

Me

+

Me,SiX

1

Consideration was given to effects, such as the acceptor properties of silicon and the silicon-halogen bond energies, which determined whether monomeric structures were retained. A mechanism for the exchange reactions was as formulated in which an intermediate, e.g. (34), was involved. hl c :I I' =N - S i hl c 3

,r

4

hlc-Si-CI I \

CI

CI

(34)

It has been found'l that the product of the following reaction sequence exists in the phosphazene (shown) rather than the aminophosphine form: Li Bu',P.NH-SiEt, +- Bu'II-i -+ But,P.N.SiEt,

Me,MCI

(hl = SI. CIC. h n )

MMe, I But,P=N Si Et

-

The l H n.m.r. spectra of these phosphazenes are straightforward when M = Ge or Sn, but when M = Si, two silicon-methyl signals appeared at room temperature. A likely reason for this observation is that the rotation of the SiMe, group is hindered and that the rate of this rotation is slow on the n.ni.r. time scale. A series of related derivatives was prepared in which the nature of the N-substituent determined whether the product was a phosphazene or aminophosphine: Li ButMeP. N. SiMe,

+ Me,SiCl

1

-

ButMeP-N(SiMe,),

Me,MCI

M Me,

I

ButMeP=N.SiMe,

Li ButMeP. N. GeMe,

1

M = G e Sn As Sb

n =3 Me3MCl

3

2

2

ButMeP- N(GeMe,)(MMe,)

(M = Si, Ge, or Sn) 0.J . Scherer and W. Gick, Chern. Eer., 1971, 104, 1490.

Orgaiiophosphorirs Chemistry

210

A novel demonstration of the strength of the Si-0 bond relative to the Si-S bond was provided during attempts to obtain the oxide and sulphide of ButMeP-N(SiMe,),:

ButMeP(S).NH .Si Me,

ButMeP.NH.SiMe,

But MeP(0)N H,

ButMeP(OSiMe,)=N. SiMe,

4 Synthesis of Cyclic Phosphazenes A re-exan~ination~~ of the reaction of ammonia with phosphorus pentachloride, which may be expressed : rlPCIb -t nNH,

-----+ (NPCI,),

+ 3HC1

has k e n reported with a view to improvement upon known routes to the chlorocyclophosphazenes. By careful control of the rate and temperature at which ammonia was added to the phosphorus pentachloride in chlorobenzene or sym-tetrachloroethane solution, it was found that the formation of unwanted linear chlorophosphazenes could be avoided completely. The overall yield of the cyclic products was therefore improved and the proportions of the lower homologues was typically: (NPCI,), Proportion

(x)

n = 3

n = 4

n = 5

66

23

6

n = 6 n = 7 3

2

The reaction was followed by 31Pn.m.r. and visualized as proceeding in stages. In the first stage, [CI,P(N=PCI,),CI]+[PCI,]- (n = 1) was formed and precipitated. This salt gradually redissolved and linear species with n = 2, 3, 4, etc. were formed. Almost immediately, N3P,C1, began to form. Yields of N3P3C16were maximized by stopping the reaction after about 5 h, by which time relatively little of the homologues, (NPCI,),, (n = 5-7), had formed. These procedures have been described in two patent applications,73*7 4 in both of which phosphorus pentachloride was prepared in situ, from white phosphorus and chlorine. In another study, 31P n.m.r. was used to follow the progress of the reaction between ammonium chloride and phosphorus pentachloride in sym-tetrachloroethane, and the mechanism of the reaction considered in some detail.75 The rate of hydrogen chloride evolution and changes in the 72

7y

74

75

G. Wunsch, R. Schiederrnaier, V. Kiener, E. Fluck, and G. Heckmann, Chew?.-Zfg., 1970, 94, 832. R. Schiedermaier, K. Wintersberger, and G. Wunsch, G.P., 1 918 697 (Chrnr. A h . , 1971, 74, 5144n). G. Wunsch, R. Schiederrnaier, and K. Wintersberger, G.P., 1 918 947 (Chen?. A h . , 1971, 74, 515Om). J. Emsley and P. B. Udy, J . Chem. Soc. ( A ) , 1970, 3025.

211

Pliosphazeries

conductivity of the solution were also used to monitor the progress of the reaction. Again the same salt was initially precipitated: 3PC15

+ NH4CI

[CI,PN=PCI,]'- [PClJ

+ 4HCI

The way in which this salt is formed is still not known with any certainty, but it may involve transient formation of a monophosphazene, CI,P=N H. It may then be that CI,P=NH effects expansion of cationic phosphazene chains: [CI,P( N= PC&) CI ] i-

+ H N =PCI, [CI,P(N=PCI,), +lCI]+

+ HCI

+

Cyclization could then occur by PCI, elimination : [CI,P(N= PCI,) ,CI]

'- -+

(NPCI,),

+ PCI,

+

The factors affecting the preparation of the cyclic chlorophosphazenes from phosphorus pentachloride and ammonium chloride continue to receive attention. For example, the yields and reaction times for the preparation of the series, (NPCI,), (n = 3-7), varied 78 with the fineness of the ammonium chloride, the nature and volume of the solvent, and added 'catalysts' such as phosphoryl chloride. A procedure, giving due consideration to these factors, was described 76 for the preparation of N,P,CI, in good yield (88% of cyclic products) and in a relatively short time (24 h). The cyclic chlorophosphazenes can be obtained in even shorter times (cn. 10 min) by addition 7 7 of four moles of pyridine to remove the hydrogen chloride formed : PCI5

+ NHdCI + 4CsHbN

1 -(NPCI,),

+ + 4C5HSNHCI-

The reaction was, of course, very exothermic, and was initiated by heating the neat reactants. A 65% yield of cyclic products was obtained. Using chlorobenzene as a solvent, the reaction was moderated and, surprisingly, took as long as 5-8 h to complete. In a comparative study 7 8 of the effects of metal halides it was found that in most cases the presence of a metal halide reduced the yield of N,P,CI,. Only in the cases of manganese(i1) chloride and molybdenum(v) chloride were improved yields obtained (39.9 and 50.0% respectively, compared with an average of 32.1% in the absence of a metal halide). A new method of purifying N,P,CI, and N,P,CI, is reported7e in a patent, whereby the hot vapours of an inert solvent such as chlorobenzene are passed through a melt (at 90 - I10 'C) i6

77

7H

J . Emsley and P. B. Udy, J . Chem. SOC.( A ) , 1971, 768. S. M. Zhivukhin, V. V. Kireev, V. P. Popilin, and G. S. Kolesnikov, Russ. J . Inorg. Chem., 1970, 15, 630. R. W. Jenkins and S. Lanoux, J . Inorg. Nuclenr Chem., 1970, 32, 2453. J . K. Maund and C. H. G . Hands, B.P., 1213 716 (Chem. A h . , 1971, 74, 89 268s).

212

Orgartophosphorirs Chemistry

of the cyclic homologues. The trimer and tetramer are preferentially vapourized and can be condensed out prior to further purification. Although no examples of iodocyclophosphazenes have yet been reported, the P=N stretching frequencies for the compounds in the series NSP3X6-,I, (X = F, CI, or Br; n = 1-6) have been estimated *O from the partial charges on the phosphorus atoms and may be useful in their identification. There is good agreement between P=N stretching frequencies calculated by this method and those observed for the halides N,P,X,-,Y, (X = F, Y = CI; X = F, Y = Br; X = CI, Y = Br; n = l--6). Previous attempts to obtain perfluoroalkylcyclophosphazenes by reactions of perfluoroalkylphosphorus(v) halides with ammonium chloride have been unsuccessful, possibly because of reactions involving carbon-phosphorus bond cleavage. However, it has now been shownE1 that the temperatures at which the reaction

proceeds can be reduced by ca. 20-30 "C using finely-dispersed ammonium chloride and that the trimeric and tetrameric products (n = 3 or 4) can be obtained in good yields. Examples of cyclophosphazenes with ring systems containing elements other than phosphorus or nitrogen continue to be reported. The linear phosphazene [Ph,(H,N)P~NllrP(NH,)Ph,]+CI- is cyclized 8 2 by antimony pentachloride to give the compound (35). This result contrasts with

that obtained with phosphorus pentachloride which gave the cyclotriphosphazatriene, N,P,CI,Ph,. The difference in reactivity was attributed to the higher base strength of the nitrogen atoms adjacent to antimony in (35) [lack of (2p5d)rr bonding] making it difficult to remove the last two moles of hydrogen chloride. This result is also analogous to the cyclization of the same phosphazene (reported last year) by Me,PCI,, where a monoprotonated species was obtained. An unusual ring system containing a phosphazene linkage was obtained 83 by the route shown in Scheme 1.

82

S. Lanoux, J . Inorg. Nuclear Chem., 1971, 33, 279. V. N. Prons, M . P. Grinblat, and A. L. Klebanskii, Zhur. obshchei Khint., 1970, 40, 2127 [ J . Gen. Chem. ( U . S . S . R . ) , 1970, 40, 21081. C. D. Schmulbach and C. Derderian, J . Inarg. Nuclear Chem., 1970, 32, 3397. H. P. Latscha and W. Klein, Z . rrnorg. Chem., 1970, 377, 225.

Phosphazenes

C1,P’

213 CI,

Me N,

CISO,NCO ,c=o---+

- 80’c

-

c1-

\N Mc

P

-L

MeN/ I

c ,1

‘ h I

o=c, ,c=o N Me

Scheme 1

5 Properties of Cyclic Phosphazenes

A. Amino-derivatives.-The reactions of sulphur halides with the monoamino-derivative, N,P,F, .NH2, have been described 83 in which the phosphazene ring stays intact despite very forcing conditions :

+

N8P3F6*NH2 SF4

90 O C ‘

N,P,F,-N=SF,

+ 2HF

The sulphur imide is hydrolytically unstable and, on standing, gives N,P3F, :

+ “=SF’

N3P3F6-N=SF2

N3P3F6

An analogous reaction occurs with thionyl chloride :

+

N ~ P S F ~ * N H ,SOCI,

reflux

N,P,F,*NSO

+ 2HCI

Several reactions of the latter product are known:

I

pyridine

N3P3F,,and ammonia are known to form a monoamino-derivative at low temperature; the same result has now been obtained with N4P4FS: N4P4F,

+ 2NH,

- 80 “C

----+ EtzO

+

N4P4F7*NH2 NH4F

This derivative readily undergoes the Kirsanov reaction and the abovenoted type of reaction with thionyl chloride: N4P4F,*NHz

+

SOCI,

N4P4F,*NS0

E. Niecke, 0. Glemser, and H. Thamm, G e m . Ber., 1970, 103, 2864. n* H . W. Roesky and W. Grosse-Bowing, Inorg. Nuclear Chem. Letters, 1970, 6, 781.

8

Orgnnophosphorrrs Chemistry

214

The possibility of using thc hexakisamino-compound, N,P,(NH,), (obtained by aninionolysis of N3P3C16),as a fertilizer for barley has been In most respects it is superior to the ammonium phosphates, although not as far as costs are concerned. There are obvious links between this application and the course of hydrolysis of N3P3(NH2),, which has recently been followed by paper chromatographic methods. An interesting series of ammonolysis and aminolysis products has been obtainedae from the cyclophosphazene (36) (see Scheme 2). I t is note-

RR1

(36)

t-

c1R R

= ==

Me R* -- ir 14, R' Mc

hl c

I Scheme 2

worthy that both dimethylamine and aniline replace chlorine by a nongeminal route to give (37) as shown by n.m.r. spectroscopy and by the properties of the fluorination product (38). The result obtained with aniline contrasts with the results of the reaction of N3P3C16and aniline, where a predominantly geminal chlorine-atom replacement pattern was observed (see below). A P-phenyl-derivative (39) of structure similar to (36) was also obtained : H,N.SO,-NH,

+ 2PhPC14

PhPCl,=N.SO,.N=PPhCl,

(39)

8p

I

+ 4HC1

(hfe38i )ZNRfr

+ 2Me3SiC1

L. Ondracek and W. Wanek, Biol. Plant., Acad. Sci. Bohemoslou., 1970, 12, 71 (Chem. Abs., 1970, 73, 3 0 6 1 ~ ) . L. Ondracek, J. Hampl, and W. Wanek, Rosrl. Vyroba, 1970, 16, 441 (Chem. A h . , 1970, 73, 76 2 8 8 ~ ) . L. Riesel, E. Herrmann, H. Patmann, R. Somieski, H . Kroschwitz, D. Schroter, and H.-A. Lehmann, Z . Chem., 1970, 10, 466. U . Bieller and M . Becke-Goehring, Z . anorg. Chem., 1971, 380, 314.

Phosplmzenes

21 5

The reactions of alkylaminofluorocyclophosphazenes with hydrogen halides have provided a route to cyclophosphazenes with mixed halogen substituents :

N,P,F,(NMe,),

+ 2HX + 4HX

N,P,F,CI(NMe,)

+ 2HBr

N3P3F4(NMe,),

--+

-

----+

N,P,F,XNMe,

+

+

+ H,NMe,X+

N,P,F,X, 2H,NMe,X(X = C1 or Br) N,P,F,CIBr

+ H,NfMe,Br-

Preparative routes to N3P3F,(NHMe),, N3P3F4(NMe2),,and N3P3F3(NMe2),,compounds with non-geminal structures, were also given. Further experiniental details, n.m.r., and i.r. data on the compounds, = 3-6, x = 1-3) and their reaction products N,P,F,,-,(NMe,),(n with hydrogen halides, already reported in preliminary form, have been given.91 Dimethylamine and Me,SiNMe, form bisdimethylamino-derivatives, predominantly with non-geminal structures. In the tetramer series, the bisdirnethylamino-derivativehas structure (40),rather than (41). The F

halides, N,,P,F,,-,X(X cy a n at o-d er iva t i ves : N,P,F,,-,X

Nh

=

C1 or Br), wcrc converted into their isothio-

+ KCNS

ITcTN _I_f

N,P,F2,-,CNS (n = 3-6)

+ KX

An extensive series of fluorocyclophosphazenes with phosphazene sideProgressive lengthening of the side-chains chains has been

@*

O9

0. Glemser, E. Niecke, and H . Thamm, Z . Narurforsch., 1970, 25b, 754. T. Chivers, R. T. Oakley, and N . L. Paddock, J . Chem. SOC.( A ) , 1970, 2324. H . W. Roesky, W. Grosse-Bowing, and E. Niecke, Chern. Eer., 1971, 104, 653.

21 6

Organophosphorus Chemistry

can be effected by successive reactions with (Me,Si),NH and phosphorus pentachloride (Scheme 3). Reactions with the more basic amine,

-

N,P, F, N H,

rC1283>

N,P,F,*N=PX3 -(Me# i )2NH ~

N3P3F,.N=PX2N=PC12.N=PCI,

N,P,F,. N=PX,NHSi Me:,

(X = F or CI)

Scheme 3

(Me,Si),NMe, not only took place at the trichlorophosphazenyl groups e.g. N,P,F, -N=PCI,

-

+ (Me,Si),NMe N,P,F,.N=PCI,*NMeSiMe,

+ Me3SiCI

but also at the phosphazene ring fluorine atoms. Methylamine, a n even stronger nucleophile, was able to displace two of the chlorine atoms in the N=PCI(NH Me),. The trichlorophosphazenyl group to give, e.g., N3P3Fb* related derivatives, N,P,F2n-1R (n = 5 ; R = NH2 or N=PCl,), were also reported. Dimethylaminolysis B3 of the novel fused ring compound (42), whose crystal structure has just been reported (see Section 7), gave a derivative of probable structure (43) on the basis of lH and 31P n.m.r. data. On the Mc,N

NMe,

/ /

NMc,

CI

N Me2

c1 Me,N (42) DS

/\

NMe,

(43)

W. Harrison, R. T. Oakley, N. L. Paddock, and J. Trotter, Chcm. Comm., 1971, 357.

Phosphazenes

217

other hand, attempted fluorination and methoxylation of (42) resulted i n the breakdown of the ring system. The donor properties of N3P3C16appear to be too weak to allow complex formation with metal halides, but it has been reported B4 that complex formation between N,P,CI, -NHBu" and Cu" or Co" chlorides in acetonitrile solutions can be detected by U.V. spectroscopy. Attempts to isolate the complexes were unsuccessful. The previously-reported alkylation reactiys of aminocyclophosphazenes by trimethyloxonium fluoroborate, Me,0BF4-, have been e ~ t e n d e d . * ~ With the dimethylamino-derivatives, N3P3Cl,-,(NMe,), (n = 1--4, or 6), a series of monomethylated derivatives, e.g. (44), was obtained, in which

/ \

CI

c1

'H n.m.r. spectroscopy showed that methylation took place on an exocyclic nitrogen atom. The salt-like nature of these products was confirmed by conductivity measurements. In contrast, the isopropylamino-derivatives, N3P3CI2( NH Pr9, and N,P3( N Me2)z(N H PI-*)^, were preferentially met hylated on the ring nitrogen atoms (the latter was also methylated at an NMe, group). The formation of (45) is interesting, since protonation of

the same base was shown by X-ray crystallography to take place at the identical ring nitrogen atom. N3P,Ph6 was, as expected, methylated at a ring nitrogen atom to give [N,P,Ph,Me]+ BF,-. Reactions of N,P,Cl, with aniline in benzene were showns6 to take the predominantly geniinal chlorine atom replacement route shown in Scheme 4. The structures were established by basicity measurements, and by the 84

R. W . Jenkins and S. Lanoux, J . Inorg. Nuclear Chem., 1970, 32, 2429. J. N. Rapko and G . Feistel, Inorg. Chern., 1970, 9, 1401. V. B. Desai, R. A. Shaw, and B. C. Smith, J . Chenr. Suc. ( A ) , 1970, 2023.

21 8

Orgcrnopliosphoriis Chemistry

(

= phosphorus atom; spokcs on rings represent incoming anilino-groups)

Scheme 4

preparation of the mixed amino-derivatives, N3P3(NMe,)6-,(NHPh),h (n = 1-5), whose lH n.m.r. spectra were examined in detail. These derivatives were obtainedfrom eitherchloroanilino- or chlorodimethylaminoderivatives, the latter being of known structure. The use of n-butylamino-derivatives of cyclophosphazenes in flameproofing cellulose-based fabrics has been described in a patent applicat i ~ n . ~The ' topic of flame retardants is also covered in a recent review,*8 where phosphazenes are important because of their relatively high phosphorus and nitrogen contents. B. Alkoxy- and Aryloxy-derivatives.-The preparation and physical properties of a series of thermally stable monoalkoxy (or aryloxy) fluorocyclophosphazenes have been reported :e9 N,P,F,

+ NaOR

Et2O

>

N,P,F,OR

+ NaF

(R = Me, Et, or Ph) Thiolysis by NaSR under the same conditions gave 9D N3P3F,SR (R = Me or Ph). Ligand-exchange reactions between a series of organo-substituted cyclotriphosphazatrienes have been studied loo and their synthetic potential demonstrated. Typical of these reactions is : Nap3(0C6H, -p-NOz)a

+ 6Na OCH,C F, N,P,(OCH,CFJ,

+ 6NaOC,H4-p-N02

(70% yield)

loo

P. Braune, H. Pohlemann, J . Swoboda, and R . Wurmb, G . P. 1 904 427 (Chenr. A h . , 1970,73, 89 052w). S. J. O'Brien, Textile Chemist and Colourisf, 1970, 2, 201. E. Niecke, H. Thamm, and 0. Glemser, Z . Nururforsch., 1971, 26h, 366. H. R. Allcock, R. L. Kugel, and E. J. Walsh, Chem. Comm., 1970, 1283.

Phosphazenes

219

An order of reactivity for a series of nucleophiles towards a given substrate could be drawn up and, in general, this follows the order: amines < alkoxides, aryloxides c organometallic reagents The latter group, including reagents such as methyl magnesium iodide and phenyl-lithium, had a considerable disadvantage in that cleavage of the phosphazene ring often occurred. Reactivity to nucfeophiles was generally increased when a five-membered ring was present at the phosphorus atom (in the phosphazene ring) so that, for example, the P-0 bond in

may be cleaved by weaker nucleophiles than in

The lability of certain alkoxy-groups has also been shown101 in the reactions:

Similar reactions with heptafluorobutoxy-derivatives have also been demonstrated. In order to obtain compounds with Ti-0-P and Zr-0-P units, the hexaethoxy-derivative, N3P3(OEt)6, was treated lo2 with titanium and zirconium tetrachlorides. I n each case, hygroscopic solids of the type N,P3(0Et),02MC12 (M = Ti or Zr) and ethyl chloride were obtained. The degree of polymerization of these solids was 1.6-1.8, and on the basis of their i.r. and 'H 1i.m.r. spectra, two alternative structures, (46) and (47), were proposed. In an alternative route to the same type of compound, N,P,Cl, was treated lo3 with tetra-n-butoxytitanium in o-xylene. Butyl chloride was liberated and a solid was obtained which has been assigned the structure (48). Its thermal decomposition was studied by differential thermal analysis. The synthesis and properties of cyclodiphosphazatrienes of type (49) and (50) are well documented. A series of P-alkoxy- and -aryloxy-derivatives V. N. Prons, M. P. Grinblat, A. L. Klebanskii, and G . A. Nikolaev, Zhur. obshchei Khim., 1970,40, 2128 [J. Gen. Chem. (U.S.S.R.L 1970, 40,21091. l o o Yu. A. Buslaev, B. V. Levin, Z. G . Rumyantseva, S. P. Petrosyants, and V, V. Mironova, Russ. J . Inorg. Chem., 1969, 14, 1711. lUs Yu. A. Buslaev, B. V. Levin, Z . G. Rumyantseva, and V. V. Mironova, Russ. J . Iitorg. Chenr., 1970,:15, 1690.

220

Organophosphorus Chemistry

OBu“ I .Ti

I

0Ru“

K

R

( 50)

(51)

of (49) and (50) has been obtained (49)

+ 4R10H + 4C5H5N (R = Ph;

lo4

by two routes. The first route:

----+

(51)

+ 4C5H,6H 61

R L = Pr” or Bu”)

was not generally satisfactory, since proton transfer from the pyridine hydrochloride to the more basic derivatives, e.g. (51 ; R = Me, R 1 = Bu”) resulted in cleavage of the ring system: (51)

H +-I?

U”OII+

--___

+

(Bu”O),P=N. P(O)(OBU~ )~ [H,N=C(Me)NH,]+ C1-

The second route:

was generally more satisfactory and was used to obtain the following derivatives : R = Me

Me

Me

R1 = Me Bun p-MeC,H,

Ph

Ph

Ph

Me

Et

p-MeC,H,

Me Et NMe2

In many cases, trialkoxy-derivatives of (49) were obtained using suitable quantities of sodium alkoxides. The 31Pn.m.r. spectra of this latter group of compounds were simpler than the tetrakisalkoxy-derivatives, enabling lflJ

A. Schmidpeter and N. Schindler, Z . ariorg. Cherti., 1970, 372, 214.

22 1

Phosphazenes

the P-N-P spin-spin coupling constants (50-64 Hz) to be obtained, which were typical of those values obtained in cyclotriphosphazatrienes. Alkoxy- and aryloxy-derivatives of (50) were obtained by both routes as mixtures of cis- and trans-isomers. It was found lo5 that N,P,CI, was progressively dehydrochlorinated by reactions with increasing molar proportions of hydroquinone. Reactions in acetone, DMF, and dioxan gave a series of decomposition products, but the addition of HOC,H,ONa to the solution enabled crystalline products, N3P3(O2C,H5),(mol. wt. 760) and N,P,(O,C,H,), (mol. wt. 940) to be isolated. The use of N,P,CI, in the synthesis of amides has been described,Ios although the fate of the phosphazene ring system was not clear: R'NIT2

R = alkyl or aryl

>

RCO-NHR'

+ 'decomposition products'

1

R1 = Et or cyciohexyl

The addition of aldehydes to N,P,CI, in the presence of pyridine has also been studied.lo7 Mention has already been made of the application of alkoxycyclophosphazenes, [NP(OR),],, as flame retardants in rayon.' Although the methoxy-derivatives, with their high phosphorus content, were expected to be most efficient in this respect, their water solubility proved a major shortcoming. However, the n-propoxy series, [NP(OPrn),],, (n' mainly 3--6), were found to impart excellent flame resistance and were well retained by rayon. The cyclophosphazene alkoxides were obtained by the addition of sodium-n-propoxide to the chloride homologues, (NPCI2),, and were added to the viscose dope before the rayon was spun. The flame resistance imparted by various amino- and thioalkoxy-derivatives was also tested, but found to be inferior to the results obtained with alkoxy-derivatives. Several patent applications have resulted from work on this topiC~lO"ll~

C. Alkyl and Aryl Derivatives.-Reactions of organometallic reagents, such as methyl-lithium, with fluorocyclophosphazenes are, in general, In5 loo

10) lo8 log

lln 111

M. Kajiwara and H . Saito, Kogyo Kagaki4 Zasshi, 1970, 73, 1947 (Chem. Abs., 1971, 74, 88 340x). G. Baccolini and G . Rosini, Chim. Ind. (Milan), 1970, 52, 583. V. K. Taksidi and B. I. Stepanov, Zhur. org. Khim., 1970, 6, 815. L. E. A. Godfrey, G . P. 2016 153 (Chem. Abs., 1971, 74, 3 2 6 2 0 ~ ) . H. Pohlemann, R. Wurmb, and P. Braun, G . P. 1906 381 (Chem. Abs., 1970, 73, 99 962g). Badische Anilin- and Soda-Fabrik A.-G., Fr. P. 2 012440 (Chem. Abs., 1970, 73, 121 501e). R. Wurmb, J. Swoboda, H. Pohlemann, and M . Jacobi, G . P. 1926 169 (Chem. Abs., 1971,74, 43 489m). R. C. Harrington, U.S.P. 3 530 204 (Chem. Abs., 1970, 73, 99 963h).

222

0rgnrr ophosph o rus Che m is t r y

cleaner than with chlorocyclophosphazenes, because ring-cleavage reactions are minimized. This feature has enabled the following derivatives to be obtained looin reasonable yields: N3P3F6

+ RLi

-

N,P3F,R

+ LiF

(R = M e o r CH=CH,)

The stepwise replacement of fluorine atoms in fluorocyclophosphazenes, (NPF,),(n = 3-9, by methyl groups has been followed.113 lH and lVF n.m,r. spectroscopy showed that methyl-lithium in diethyl ether generally effects a geminal replacement pattern. With N3P3F6, only mono- and di-methyl derivatives were obtained, but with N4P4FBthe dimethyl (52), trimethyl (53), and octamethyl derivatives were noted. The formation of Mc

Me

/ \

F

1-‘

Me

Me

/I

F Me

(53)

compounds of structure (52) and (53) is unexpected on simple electrostatic grounds, since reactions with nucleophilic species would be expected at fluorinated rather than at methylated phosphorus atoms. I t has been suggested that the formation of these two structures may be understood in terms of substitution at the phosphorus atoms with the least n-induced negative charge, Huckel-type molecular orbital calculations show that increasing r-induced negative charge on the phosphorus atoms in (52) follows the order: P-1 < P-3 < P-2, i.e. so that P-2 is least attractive to nucleophiles, as found. A decamethyl derivative, N5P5Me10, was also reported.

The first example of an optically active cyclophosphazene (54) has been obtained 114 by elegant experimental work. The route chosen is summarized in Scheme 5.

114

N. L. Paddock, T. N. Ranganthan, and J. M. Todd, Cunad. J . Chetn., 1971, 49, 164. C. D. Schmulbach, C. Derderian, 0. Zeck, and S. Sahuri, Inorg. Chenr., 1971, 10, 195.

223

Phosphazenes

Scheme 5 A detailed description of the experimental aspects of the preparation of the fluorophenylcyclotriphosphazatrienes(56) and (57) has been given.ll’

(55)

I’Ill,i

I’IIII- 4lC‘la

( 5 6 ) ---A (57)

The near-u.v. absorption spectra of a series of halogenophenylcyclotriphosphazatrienes, N3P3X6-,Ph, [X = F, n = 2 (3 isomers), n = 4 (geminal isomer); X = F, n = 5 ; X = Cl, n = 2 (geminal isomer), n = 4 (geminal isomer); n = 61 have been compared 116 and suggest that weak conjugation takes place between the phenyl groups and the phosphorus atoms. A new borohydride derivative of a cyclophosphazene has been obtained

116 ‘17

C. W. Allen and T. Moeller, Inorg. Synth. 1970, 12, 293. A. J. Wagner and T. Moeller, J . Inorg. Nuclear Chetn., 1971, 33, 1307. N. T. Kuznetsov and G . S. Klimchuk, Russ. J . Inorg. Chern., 1970, 15, 1496.

224

Organophosphorus Chemistry

D. Pseudohalogeno-derivatives.-Little work has been carried o u t in this area. Isocyanates of cyclic phosphazenes, previously unknown, are thought lr8 to be formed in the reaction of N,P,Br, with AgOCN in nitromethane. They were detected by i.r. spectroscopy, and underwent ready polymerization, which precluded their isolation. On the other hand, isothiocyanates, [NP(NCS),], (n = 3 or 4), are well known and a detailed study of their spectra has been reported.llQ The azide, N3P3(N3),,has been the subject of an i.r. study which suggests120that the molecule has D3,, symmetry. 6 Polymeric Phosphazenes

Linear phosphazene polymers, obtained from the reaction of ammonium chloride with phosphorus pentachloride in chlorobenzene, may be rendered hydrolytically stable by reaction 131 of one of the terminal chlorine atoms with, for example, sodium phenoxide: C1[N=PCI2].PCI4

+ NaOPh

(mol. wt. -800)

-

CI[N=PCI,],PCI,OPh

+ NaCI

Dimethylamine, aniline, phenol, and ethanol have also been used with similar effect. The monophosphazenes, CI,P=N. P(OjCI,, and Ph,PCl= N P(O)CI,, give polymers of the type CI[CI,P=N],,* [PCI=N],,; P(O)CI,

(X = Ph, Y = CI)

I

N=PX,Y

when heated together.*22 When Et,P=N P(O)CI, was used, a similar polymer (X = Y = Et) was obtained. The thermal decomposition of (NPCI,), (linear polymer) follows first-order kinetics and has an activation energy of 22.5 kcal mol-l. Decomposition is thought to be initiated at the ends of the macro-chain and gives products which include a wide range of cyclic and linear phosphazenes. The properties of fluoroalkoxyphosphazene polymers and copolymers [N=P(OR),], (R = fluoroalkoxy-group) have been described.124 Condensation of the phosphazenes, (CI,PNPhj, and C,N,(N= PCI,),, with 6

lln 118

IZ0

lz3 lZ4

E. Steger and G . Bachmann, Z . Chem., 1970, 8, 306. A. J. Wagner and T. Moeller, J . Chem. SOC.( A ) , 1971, 596. F. Rauchie and M. Gayoso, Ann. Fis., 1970, 66, 241 (Chem. Ahs., 1971, 74, 58 865e). R. G. Rice, R. M . Murch, and D. C. De Vore, U.S.P. 3 545 942 (Chetn. Abs., 1971, 74, 54 398g). A. Ya. Yakubovich, I. M. Filatova. E. L. Zaitseva, and V. S. Yakubovicli, Vysokond. Soedineriii Ser. A , 1970, 12, 585 (Chmi. Ahs., 1970, 73. 458 935s). J . R. MacCulluni and A. R . S. Wernick, J . Mncmriiol. Sci. Clierri., 1971, 5,6 5 I (C'/wtii. Abs., 1971, 75, 64 569c). S. H . Rose, K . A. Reynard, and J. R . Cable, US. Clearinghouse Fed. Sci. Tech. Inform., A D 1970, No. 704 332 (Chetn. Abs., 1970, 73, 99 778b).

Phosphazenes

225

urea or with melamine gave a new series of polymers whose thermal stability has been examined.lZ6 The reactions of chlorosilanes with alkoxyphosphazenes have already been mentioned (Section 3). This type of reaction has been exploited 126 to obtain polymers containing

I

I

I

I Me

-N=P-O-CH2-Si-O-

units from alkoxycyclophosphazenes, N3P3(OR)6,and oligomeric chloromethylsiloxanes. Other polymers have been reported from the reactions of N3P3C16with alkoxyboron the sodium salt of hydroquinone,128 and 4,4'-dihydroxybiphenyl . l Z 9 n6 S. M. Zhivukhin, V. V. Kireev, S. S. Titov, and G. S. Kolesnikov, Trudy Mosk. Khim.-Techknol. Inst., 1969, 200 (Chem. Abs., 1970, 73, 15 3542).

127 la8

128

V. V. Kireev, I. M . Raigorodskii, and G. S. Kolesnikov, Plust. Massy., 1970, 26 (Chenr. Abs., 1971, 74, 32 246d). A. V. Deryabin, S. M. Zhivukhin, V. V. Kireev, and G. S. Kolesnikov, Trudy Mosk. Khinr.-Teckhnol. Inst., 1969, 206 (Chem. Abs., 1970, 73, 15 630m). T. Okuhashi and Y. Watanabe, Kogyo Kugaku Zasshi, 1970, 73, 1164 (Chem. Abs., 1970, 73, 1 I0 187f). M. Kajiwara and H . Saito, Kogyo Kagaku Zasshi, 1970, 73, 1954 (Chenr. Abs., 1971, 74, 76916b).

1.567 (6)

P-N

(A)*

P

,NCS

D

,CI

13'

133

13*

131

130

1.581 (5)

1.575 (7)

P-c

P-N 1.63 119

121

102.1 ( I )

1 1 8.5 (5)

2.162 (4)

P-Br

121.4 (3)

142 (1)

1 1 8.4 (2)

d

XNX

/\

124.2 (5)

("I*

1.993 (2)

P-CI

1.79

-

I

NPN

I\

Comments

plane. PNC = 152"

/\

Ring planar except for one N atom which is 0.15 8, out of

ficantly different PNP angles (119.3 and 122.4")

/'A

Improved structure determination. Slight chair conformation, signi-

Improved structure determination. Greatest difference from previous results is in P-CI bond lengths (before 1.97 A)

Four of the phenyl groups bonded to P-N-P unit have conformations similar to the phenyl groups in N3P3C12Ph4

P-N shorter than in Ph,FP=NMe (1.641 A). N-Aryl group 35" out of P-N-C plane

Diffraction Methods

Average bond annles -

M. J. E. Hewlins, J . Chem. Soc. (B), 1971, 942. L. B. Handy, J. K. Ruff, and L. F. Dahl, J. Amer. Chem. SOC.,1970, 92,7312. L. B. Handy, J. K. Ruff, and L. F. Dahl, J. Amer. Chem. Soc., 1970, 92,7327. G. J. Bullen, J. Chem. SOC.( A ) , 1971, 1450. H. Zoer and A. J. Wagner, Acra Cryst., 1970, B26, 1812. J. B. Faught, T. Moeller, and I. C. Paul, Inorg. Chem., 1970, 9, 1656.

*Standard deviations in parentheses.

SCN\

Cl,

[Ph3PIIINEPPh3]+[Cr2(CO),,l]-

1.80

P-c

1.809 (8)

P-x P-c

Average bond distances

[Ph3PIIINfflPPh3]2+[M2(CO),,]2-CH,CI, 1.570 (15) (M = Cr or Mo)

Compound

7 Molecular Structures of Pbosphazenes Determined by &Ray

135

I34

133

132

131

130

Ref.

P

,OPh 117.3 (3)

118.5

P-0 1.584

NPN

1.582 (2)

P-0

P-x

P-F 1.52 (1) P-C 1.81 (1)

P-8N-1 1.59 (1) P-2N-1 1.53 (1)

N- 1P-2N-3 125.9 (9)

XNX

134.6 (7)

121.0

121.9 (3)

6

NP-8N-1 117.5 ( 5 )

As preliminary report (Vol. 1 )

1.575 (2)

P-N

/\

("I*

(A)* /\

Acerage bond angles

Arerage bond distances

Me 'Me *Standard deviations in parentheses. la6 W. C. Marsh and J. Trotter, J. Chew?.Soc. ( A ) , 1971, 169. l S i H. R. Allcock, M. T. Stein, and J. A. Stanko, Chem. Comm., 1970, 944. 138 N. V. Mani and F. H. Ahmed, Acta Crysf., 1971, B27, 51. l J 0 W. C. Marsh, T.N. Ranganthan, J. Trotter, and N. L. Paddock, Chem. Comni., 1970, 815. I4O W. C. Marsh and J. Trotter, J. Chern. SOC.( A ) , 1971, 573. 141 W. C. Marsh and J. Trotter, J.Chern. Soc. (A), 1971, 569.

Me, ,Me

N,P,CI,( NHPr'),HCI

PhO,

Compound

Ring has 'saddle' conformation. Variation in P-N bond lengths consistent with n-bonding theory

Three independent P-N bond lengths. OPO = 102.7"' exocyclic groups twisted at 48" to average plane of phosphazene ring

P-0-C = 123", ring slightly nonplanar with two N atoms 0.15 8, out of plane of other four atoms

Comnients

139, 141

138

137

136

Ref.

5

3

Z,

$

b

3-

N

CI

\

F

14'

143

14*

P-x

1.601.65 (2) (N-CU bonded) 1.531.57 (2)

i

P-N 1.621.68 (2)

P-F P-8N-1 1.4811.584 P-2N-1 1.495 (8) 1.470 (6) P-c P-2N-3 1.794 (8) 1.532 P-4N-3 1.487

P-N

(A)*

Acerage bond distances (O)*

XNX

/\

97.2115.4

119.G 122.4

Others 124.6, 126.1

NP-8N-1 116.9 ( 5 )

132.4137.6

133.2141.8

Other 143.3 (6)

P-8N-1P-2 146.7 ( 5 )

nA

NPN

/\

Average bond angles

G. J. Bullen and P. A. Tucker, Chem. Comm., 1970, 1185. W. C. Marsh, N. L. Paddock, C. J. Stewart, and J. Trotter, Chem. Conrm., 1970, 1190. W. C. Marsh and J. Trotter, J . Chem. SOC.( A ) , 1971, 1482.

*Standard deviations in parentheses.

[N,P,( N Me,) ,,CuCI]-CuCI,-

/L

Ph

C1

Ph

F

/ P\

\a/

3

/F

'2P\ /

IN\

F

F \ /N P / \ F N

/ 8 \

P

Me\ / Me

Compound

5-co-ordinated Cu on C, axis. NMe, groups nearly planar

Flattened crown conformation

Contains shortest known P-N bond (1.470 A). Alternation of P-N bond lengths may be explained in terms of .rr-bonding

Comments

143, 144

142

139, 140

Ref.

-4

.=.

2

3

2

s

h

2 g

0

00 w

t3

c ,1

I

x

Ph

II Ph

P' \

14'

146

PN-P 1.597 (2) CN-P 1.608 (2)

PN-P 1.567 (3) CN-P 1 A20 (3)

P- 1N-2 1.571 P-3N-2 1.558 P-3N-4 1,723

P-N P-x

-

P-c 1.802 (2)

P-c 1.801 (2)

P-3-Cl 2.004

P-1-CI 1.979

(A>*

Average bond distances (O)*

XNX

/\

Comments

115.4 (2)

-

-

117.1 (lo) 115.4 (10)

116.5 (2)

F

/ \

F

One form has cis-frans orientation in repeating unit, i.e. F F, / /P=N, N P=

Skew boat conformation. NMe, group planar and in plane of phosphazene ring

Slightly non-planar, in skew boat conformation

P-IN-2P-3 Central NP, almost planar, but other N and P atoms puckered 125.5 A out of this plane N-2P-3N-4 104.0

NP-1N-2 116.9

NPN

/\

Average bond angles

D. R. Pollard and F. H. Ahmed, Acta Crysf., 1971, B27, 163. D.R. Pollard and F. H. Ahmed, Acta Crysr., 1971, B27, 172. H.R. Allcock, G . F. Konopskii, R. L. Kugel, and E. G . Stroh, Chem. Comm., 1970, 985.

*Standard deviations in parentheses.

N

/

N//C'N

Ph\l yh/P+

Ph

II /Ph /p\ N Ph NMe,

2,

Pl1,I

N//C"

I

Me

CI

P N/l>N C1,II 3 iC ,1 2% /p+. " N C1i, I

CI,

Compound

147

146

145

93

Re; b

:

tu

$-

0

s

I0 Rad ical, Photochemical, and Deoxygenation Reactions BY R. S . DAVIDSON

1 Radical and Photochemical Reactions The formation of diphenylphosphino radicals on photolysis of triphenylphosphine,'. diphenylphosphine,l and tetraphenylbiphosphine 1 r has been verified. In the case of the reactions of the phosphines, the radicals were trapped with t-nitrosobutane and the resultant nitroxyl radical [Ph2PN(b)But]was identified by e.s.r. The nitroxyl radical has a small 31P splitting constant, demonstrating that there is no extensive delocalization onto the phosphorus atom. The e.s.r. spectrum of diphenylphosphino radicals, generated by photolysis of tetraphenylbiphosphine in benzene at 77 K, has been o b ~ e r v e d .When ~ methanolic solutions of the biphosphine or triphenylphosphine are flash-photolysed, a transient species having A,,,,, = 330 nm and which decays by first-order kinetics (k 4 x 10 -3 s-l) is observed. The absorption spectrum was assigned to the diphenylphosphino radical. The validity of the previous claim that diphenylphosphino radicals abstract hydrogen from the 0 - H bond of alcohols has been questioned, Irradiation of the biphosphine in deuteriated methanol (MeOD) was found to produce unlabelled methanol. Reaction by abstraction of hydrogen from the a-C-H bond of the alcohol was postulated as N

ill.

Ph2P-PPh, -+ Pt1,P.

+ CH,OL) + Ph,PII + .CH,OI> Ph,Pli + CH3013 --+ Ph,PD + CFl,OIi

Ph,P-

shown. However, products derived from the hydromethyl radical (.CH,OH) have not been detected. In the case of the reaction of the radicals (produced from triphenylphosphine) with propan-2-01, it was conclusively shown that acetone was not produced. Formation of this compound would be expected if abstraction from the a-C-H bond had occurred, Clarification of this situation is awaited with interest. a

H. Karlsson and C. Lagercrantz, Acta Chem. Scand., 1970, 24, 3411. S. K. Wong, W. Sytnyk, and J. K. S . Wan, Canud. J. Chem., 1971, 49, 994. S. K. Wong and J. K. S. Wan, Spectroscopy Letters, 1970, 3, 135. R. S. Davidson, R. Sheldon, and S. Trippett, J . Chem. SOC.( C ) , 1966, 722; Chem. Comm., 1966, 99.

Radical, Photochemicd, and Deoxygetiririon Recrcfioiis

23 1

The formation of the biphosphines ( 1 ) and (2) by reaction of tetramethylbiphosphine with buta-l,3-diene has been rationalized in terms of participation of dimethylphosphino radicals as intermediates.5 Reaction

(2)

(1)

by the concerted addition of the biphosphine to the cis-diene could be ruled out since only (1) should have been formed by this route. It was shown that (1) and (2) are not equilibrated under the reaction conditions. The reaction with isocyanides of phosphino radicals, generated by the reaction of secondary phosphine with AIBN, gives the nitrile (4) as well as the expected product (3).6

Et,P*

+ RNC

t t-l’t I

---+

EtLPC=NR -+

I

P-rLi\sion

Et,PCN

+ R.

I t ,PI!

I’tLPCH:NR (3)

RII

+ T3t,P-

(4)

Phosphinyl radicals, obtained by hydrogen abstraction from dialkyl phosphites, have been trapped with t-nitrosobutane and the resultant nitroxyl radicals examined by e.s.r.l The reaction of phosphinyl radicals, e.g. ( 5 ) and (6), with olefins has been shown to occur with retention of configuration at p h o s p h o r u ~ . ~These - ~ ~ radicals have also been postulated as intermediates in the reactions of dialkyl disulphides and diary1 disulphides with pho~phinates.~-l~ From the reaction of diphenyl disulphide 0

0 I1 .I’

Pr’0‘‘I ‘1 1 MC

0

-

0

I1

/If,

p

priO.

hl c

--+

0 II

~ i ~ ~ p - l - t ~p,.iO../’\ iic

hl c

GH,5

(6)

’ lo

W. Hewerston and I. C. Taylor, J . Chem. SOC.( C ) , 1970, 1990. T. Saegusa, Y. Ito, N. Yasuda, and T. Hotaka, J . Org. Chem., 1970, 35, 4238. G. R. Van den Berg, D. H. J . M. Platenburg, and H. P. Benschop, Chem. Conim., 1971, 606; H. P. Benschop and D. H. J. M. Platenburg, Chem. Comm., 1970, 1098. L. P. Reiff and H . S. Aaron, J . Amer. Chem. SOC.,1970, 92, 5275. W. B. Farnham, R. K . Murray, and K. Mislow, Chem. Comrn., 1971, 146. W. B. Farnham, R. K. Murray, and K. Mislow, Chern. Cornm., 1971, 605.

232

0rganophosphor11s Chemistry

it appears that the reaction with thiyl radicals also occurs with retention at phosphorus.8 Since the products from reaction of phosphinyl radicals with olefins can be correlated with those from reaction of dialkyl phosphites with disulphides, e.g. (7), by means of a Grignard reaction it follows that this latter reaction occurs with retention of configuration at phosphoru~.~1 lo 0 P

RO"j '€1 Me

0

0 II

II

R'S'

1'

RO,.l

hl c

II

R' S S I<'

.P

RO"I 'SRl hle

--+

+

(7)

R'SI 1

I

The peroxide-catalysed addition of dimethyl phosphonate to norbornadiene gives nortricyclenes as well as norbornenes." Usually, radicals react with this diene to give only nortricyclene derivatives. The ease of hydrogen abstraction from the parent phosphonate undoubtedly favours trapping of radical (8). Further evidence has been adduced for the configurational stability of phosphoranyl radicals.12 Thus photolysis of iodobenzene in the presence of (11) gave a 95% yield of (12). Reaction of the phosphonium salt (13) with lithium alkyls produces the phosphoranyl radical (14).13 The formation and reaction of peroxyl radicals derived by reaction of tervalent phosphorus compounds with oxygen have attracted interest. Photolysis of trialkyl phosphites in oxygenated solutions of aromatic hydrocarbons gives phen01s.l~'~Phosphorus trichloride reacts with I ,2dichloroethylene, in the presence of oxygen, to give (17).14*It is tempting to suggest that both reactions occur via similar intermediates, e.g. (15) and (16). Anodic oxidation of the diphenylmethylenephosphorane (1 8) has been shown to give the radical (19).15 The 31Pcoupling constant for the radical shows that little delocalization of the unpaired electron onto the phosl1 la

lS I&

H. J. Callot and C. Benezra, Canad. J . Chem., 1971, 49, 500. W. G . Bentrude and K. C. Yee, Tetrahedron Letters, 1970, 3999. D. Hellwinkel and H.-J. Wilfinger, Annalen, 1970, 742, 163. R. Higgins, K. M. Kitson, and J. R. L. Smith, J . Chem. Suc. (B), 1971, 430. C. B. C. Boyce and S. B. Webb, J . Chem. Soc. ( C ) , 1971, 1613. H. M. Buck, A. H. Huizer, S. J. Oldenburg, and P. Schipper, Rec. Trav. chim., 1970, 89, 1085.

Radical, Photochemical, and Deoxygenntioti Reactiotts

233

234

Organophosphorus Chemistry

I

phorus atom occurs. Electrolytic reduction of methyldiphenylphosphine gives a radical ion by addition of an electron to the phenyl group.lG The 31Pcoupling constant for this radical was found to be temperature dependent. The use of HMPT as a solvent for the electrolysis of sodium diethyl malonate was found to lead to (20) and (21).17 l8

P. Gerson, G . Plattner, and H. Bock, Helo. Chim. Acto, 1970, 53, 1629. R . Brettle and D. Seddon, J . Chern. SOC. ( C ) , 1970, 1153.

Radicd, Photochemical, and Deoxygentltion Reactions

23 5

Tri-( 1-naphthy1)phosphine is cleaved by alkali metals in TH F solution.lH Reaction with sodium gives the naphthalene radical-ion, with lithium the perylene radical-ion, and with potassium the radical-ion (22). Hydrocarbon radical-ion formation was thought to occur via naphthalene derived from the metal naphthalenide. E.s.r. spectra of further examples of phosphorussubstituted picrylhydrazyl radicals have been reported.lB

Phosphinidenes have been postulated as intermediates in the addition of cyclopolyphosphines to conjugated dienes 2o and in the thermal decomposition of (23).21 Isolation of the adduct (24) from decomposition of (23) in Ph ir

11

I 1 I’hP, ,,PPh II 0 II 0 0 (23)

---+

1

PhP(OH), II 0

+ PhP:

twwil

MPh

0, ,O ,P,Ph 0 0 Ph

M PI1 (24)

In ‘Lo

M . H . Hnoosh and R . A. Zingaro, J . Amer. Chem. SOC.,1970, 92, 4388. K. Leibler, K. Okon, and E. Checinski, J . Chim. phys., 1970, 67, 746. A. Ecker, I. Boie, and U. Schmidt, Angew. Chem. Infernat. Edn., 1971, 10, 191. M . J. Gallagher and I. D. Jenkins,J. Chem. SOC. (C), 1971, 593.

Organophosphorus Chemistry

236

the presence of benzil was taken as evidence for the intermediate. Decomposition of cyclopolyphosphines in the presence of sulphur gave the anhydrides (25) which react with dienes to give products of the type (26) in high yield. R

The reactions of benzyne 2 2 and carbenes 23 with phosphabenzenes and of carbenes with p h o ~ p h o l e have s ~ ~ been investigated. Whereas benzyne reacted in the anticipated manner with (27) to give (28), carbenes, or their precursors, reacted in a curious manner to give substituted benzenes (30). Good evidence for the intermediacy of the phosphepin (29) came from the finding that closely related compounds, such as (31), also decomposed to give substituted benzenes. The nature of the eliminated phosphorus entity has still to be determined.

Photolysis of the phosphonium salt (32) ( A > 200nm) gives products derived by paths A and B.25 The mechanisms of formation of other isolated products, e.g. ethyl phenylacetate and biphenyl, are not so obvious. The relative efficiency of the two reaction paths is solvent dependent, path B being favoured by solvents of low polarity. Irradiation and thermolysis of the quinquecovalent phosphine (33) result in the elimination of triphenylphosphine.2s The azido-phosphetan oxide (34) gives both ring-expansion and ring-cleavage products on p h o t o l y ~ i s . The ~ ~ two ring-expansion products (35) and (36) are obtained in about equal yield. If the reaction is occurring via a nitrene intermediate, it is peculiar that there is little preference for the migration of the tertiary carbon atom compared with the primary carbon atom. 22

23 24 26

*II 27

G . MBrkl, F. Lieb, and C. Martin, Tetrahedron Letters, 1971, 1249. G . MBrkl and A. Merz, Tetrahedron Letters, 1971, 1269. A. N . Hughes and C. Srivanavit, Canad. J . Chem., 1971,49, 874. Y . Nagao, K. Shima, and H. Sakurai, Tetrahedron Letters, 1971, 1101. T. J. Katz and E. W. Turnblom, J . Amer. Chem. SOC., 1970, 92, 6701. M. J . P. Harger, Chem. Comm., 1971, 442.

Radical, Photochemical, and Deoxygeriation Reactions

1’11

237

238

Orgutlophosphorits Chemistry

2 Desulphurization and Deoxygenation Reactions

Dialkyl thiosulphonates (37) are desulphurized by tris(diethy1aniino)phosphine to give sulphoxides.28 In some cases sulphinate esters are formed as minor products. Diary1 thiosulphonates gave 1 : 1-adducts of the type (38). Desulphurization of sulphenimides (39) by tris(dimethy1amino)phos-

ii

ii

(37)

phine has been used as a method for the conversion of thiols into alkyl arnines.2g Deoxygenation of sulphenate esters, derived by reaction of (39) with alkoxides, with trialkylphosphines gives sulphides.sO Surprisingly, this reaction is not affected by the use of alcohols as solvents and intermediate (40) is thought to exist as a tight ion-pair. This contrasts with the previous finding that the intermediate (41), produced in the reaction of

30

D. N. Harpp, J. G. Gleason, and D. K. Ash, J . Org. Chern., 1971, 36, 322. D. N. Harpp and B. A. Orwig, Tetrahedron Letters, 1970, 2691. D. H. R. Barton, G. Page, and D. A. Widdowson, Chern. Comni., 1970, 1466.

RCtdicul, Photo diemical, rmd Deoxyget ICI t io ti R ca c t iot is

239

+

(Mc,N),P S K s I< (41)

dialkyl disulphides with tris(dimethylamino)phosphine, exists as a dissociated phosphoniuni salt rather than as a tight ion-paira31 The fact that trialkyl phosphites deoxygenate sulphenates to give thiols has been used to show that the penicillin derivative (43) is produced from (42) by a thermal sigmatropic shift.32

ot1 I

\

'-I

(43)

Desulphurization of the disulphide (44) has been shown to result in epimerization at the asymmetric carbon Synthetic applications of

31 33

53

D. N. Harpp, J. G . Gleason, and J. P. Snyder, J . Arner. Chem. SOC.,1968, 90, 4181. L. D. Hatfield, J . Fisher, F. L. Jose, and R. D. G . Cooper, Tetrahedron I>etters, 1970, 4897; R. D. G. Cooper and F. L. Jose, J . Amer. Chem. SOC., 1970, 92, 2575. S. Safe and A. Taylor, J . Chem. SUC.(C), 1971, 1189.

240

Organophosphorus Chemistry

desulphurization reactions include the formation of the thietone (46) from (45) 34 and of olefins from oxathiolan-5-ones (47) 35 and azo-sulphides, r.g. (48).36 For reaction with oxathiolan-5-ones to be effective, the R

groups have to be aryl, presumably because they facilitate the loss of carbon dioxide. The thiepin (49), a stable 877 system, is desulphurized on heating with triphenylphosphine to give (50).37

34

s5

:Ii

A . Padwa and R . Grubber, J . Org. C‘hciri., 1970, 35, 1781.

D. H . R. Barton and B. J. Willis, Chenr. Conrni., 1970, 1225. D. H. R. Barton, E. H. Smith, and B. J. Willis, Chem. Comm., 1970, 1226. J . M . HofTmann and R. H . Schlessinger, J . Amer. Chem. Soc., 1970, 92, 5263.

Ph,P

R

(51)

I

R'

=

allql or aryl

XNHCHCo2H rc'action B

spy

Y =

protecting group

R1 + I Ph,POCO*CHNHX

(51)

+ PgS-SPY +Ph,PSPy

+ (51)

I

R

I

0

I1 II R'OP-0-P-OR I I OH OH

0

R I XNHCHCO-NHCHCO, Y

reaction A

4-

Ph,PSPy

0

I1 ROP(OH); ~

0

OH

I

II R'OP-OR

0

It Ph,POP(OH) OR

+

$

b

>

242

Or~nrtophosphorirsChemistry

The reaction of dipyridyl disulphide with triphenylphosphine to give the stable phosphonium salt ( 5 1) has been used in new methods of phosphorylation (reaction A),3Hin peptide synthesis (reaction B),39and in the formation of active esters of or-amino-acids (reaction C).40 These reactions appear to have synthetic potential. The deoxygenation of peroxycarbonates (53) with phosphines and phosphites has been e x a n ~ i n e d Reaction .~~ with phosphites favours pyrocarbonate formation (Path A) whilst phosphines favour carbonate formation (Path B). Secondary phosphine oxides are oxidized to phosphinic acids by perbenzoic acid.42 The kinetics of the deoxygenation of hydroperoxides by triphenylphosphine have been examined and the reaction shown to be catalysed by strong R'OCO*OCR'

I/

I1

-

0 0 S -= R or RO \\,here K alkyl or nryl T

x $1'

0

I1 X,PO-C,-O~* 4-

\

d X,P=O

.A ; ; , ' 6: - - -'I3

Rl

~

I1

+

R'OCOCORl II It

0 0

0

(53)

R'OCOR' I1

0

+ CO,

+ X,PO

There is a continuing interest in the use of phosphite-ozone adducts as sources of singlet oxygen and as reagents for mimicking the reactions of this species. The commercially available phosphite (54) forms an ozone adduct of striking stability.44 Decomposition of the adduct only becomes appreciable at temperatures > 0 "C; the decomposition exhibits first-order kinetics, so that at 10 "C k = 9.10 x niin-' and t i = 76.2 min. These

3R

38 40

4a 43 44

T. Mukaiyama and M. Hashimoto, Bull. Chern. SOP.Japan, 1971,44, 196; Tetrahedron Letters, 1971, 2425. T. Mukaiyama, R. Matsueda, and M. Suzuki, Tetrahedron Letters, 1970, 1901. T. Mukaiyama, K . Goto, R. Matsueda, and M. Ueki, Tetrahedron Letters, 1970, 5293. W. Adam and A. Rois, J . Org. Chern., 1971, 36, 407. R. Curci and G. Modena, Tetrahedron, 1970, 26, 4189. R. Hiatt and C. McColeman, Cunud. J . Chern., 1971, 49, 1712. M. E. Brcnnan, Chern. Cornm., 1970, 956.

Rndicnl, Pliotocliemicnl, nnd Deoxygeriotion Renctions

243

values differ considerably from those for the triphenyl phosphite--oLone adduct, k = 1.47 n1in-l and t i = 0.47 niin at 10 " C . Decomposition of the adduct in the presence of tetraphenylcyclopentadienone gives products typical of the intermediacy of singlet oxygen. Reaction of the triphenyl phosphite-ozone adduct with cis- and trans- 1,2-diethoxyethylene has been shown to give a mixture of 1,2-dioxetans of very similar omp position.^^ Since the starting olefins are not isomerized under the reaction conditions, isomerization is proposed as occurring in intermediates ( 5 5 ) and (56). The

+

I

OEt (55)

+

p-(O El0

qO-[ +-

OEt

OEt 1 7(':,

0-0 EtO *on

(56)

83:;

efficiency of rotational equilibration would be hard to rationalize on the basis of a single 1,4-biradical or 1,4-dipolar species. Dialkyl disulphides are oxidized to thiosulphinates and thiosulphonates by the triphenyl phosphite-ozone adduct at temperatures below that required for singlet oxygen formation, and therefore it is probable that this reaction also involves ionic interrnediate~.~~ Trifluoroethanol has been shown to promote the addition of nitrenes, generated by the reaction of nitroso-compounds with phosphites, to aromatic hydrocarbons, e.g. (57), (58), and (59) are formed from the reaction

(57)

(58) 3-

yH,NHPh

46

4e

A. P. Schaap and P. D. Bartlett, J . A m w . Chem. Soc., 1970, 92, 6055. R. W. Murray, R. D. Smetana, and E. Block, Tetrahedron Letters, 1971, 299.

244

Organophosphorirs Chemistry

of nitrosobenzene with triethyl phosphite in the presence of mesitylene and the Reaction of nitroso-compounds with phosphites in alcoholic solutions containing acid gives products derived by reduction of the nitroso-group and substitution of the alcohol into the aromatic ring.** It is suggested that reaction occurs via an intermediate of the type (60). This may either be protonated, eventually to yield substitution products, or else decompose to give a nitrene. Kinetic measurements of the reaction of triethyl phosphite with a variety of substituted nitrosobenzenes have been made4e and these indicate that the rate-determining step is nucleophilic attack of the phosphite upon the oxygen atom of the nitroso-group to give an intermediate like (60). L

t

H NOP(0 K )3

The kinetics of formation of phosphonates by reaction of o-dinitrobenzene with phosphites have been examined.60 The energy of activation for the reaction increases as the nucleophilicity of the phosphite decreases, e,g, ethyl diphenylphosphinite 14 kcal mol-l, diethyl phenylphosphonite 16 kcal mol-I, and triethyl phosphite 21 kcal mol-I. An intermediate of the type (61), formed by nucleophilic attack of the phosphite, was proposed. In (61) there is a particularly favourable electrostatic interaction. That p-dinitrobenzene is unreactive, is thought to stem from the fact that this compound cannot form an intermediate with such a stabilizing factor. It has been pointed out,61 in the full paper describing the formation of (64) by deoxygenation of the nitrobenzoxazole (62), that the reaction can be rationalized in terms of an intermediate nitroso-compound (63) or compound (65). Further synthetic applications of the deoxygenation of nitro-compounds have been described, e.g. the syntheses of (66) 62 and (67).63 There has been " " 4s 6o 61 62

63

R. J. Sundberg and R. H. Smith, Tetrahedron Letters, 1971, 267. R. J. Sundberg and R. H. Smith, J . Org. Chem., 1971, 36, 295. R. J. Sundberg and C.-C. Lang, J . Org. Chem., 1971, 36,300. J. I . G . Cadogan and D. T. Eastlick, J . Chem. SOC.(B), 1970, 1314. A. J. Boulton, I. J. Fletcher, and A. R. Katritzky, J . Chem. SOC.( C ) , 1971, I 93. K. E. Chippendale, B. Iddon, and H. Suschitzky, Chem. Comm., 1971, 203. J. I. G . Cadogan, R . Marshall, D. M . Smith, and M. J.Todd,J. Chem. SOC. ( C ) , 19 0,244 I .

Radical, Photochemical, and Deoxygenation Reactions

245

I

R

9

246

Organophosphorus Chemistry

I! (67)

further interest in the rearrangement reactions which take place on the formation of phenothiazines by cyclization of nitrenes derived from 2-nitrophenyl phenyl sulphides, e.g. in the formation of (68) and (69).54*66 0M c

o.2Me

-xz-+ /

'N: 0' Mc

,.'

../' J 0@I-

;,

I

bhlc

(69) b4 65

J . I. G . Cadogan and S. Kulik, Chem. Cotnm., 1970, 792. J . 1. G . Cadogan, S. Kulik, C. Thomson, and M. J. Todd, J . Chem. Soc. (C), 1970, 2473.

Rriclictrl, Plioroclieaiictrl, arid Deoxygencrtion Reactions

247

The efficient conversion of the furazans (70) into 1,4-dinitriles (71) is thought to occur #in the nitrile oxides (72).6s Thermal decomposition of the diaziridones (73) in the presence of triethyl phosphite gives the phosphine-imine (75) and the isocyanate (74), which subsequently react together to give the carbodi-imide (76).67

0 I1 C /\

IIN-N-R

(73)

6E G7

(EtO),P __J

RNCO (74)

+

(EtO),P=NR (75)

T. Mukai and M . Nitta, Chent. Conim., 1970, 1192. F. D. Grecne, W. R. Bergmark, and J. F. Pnzos, J . Org. Chem., 1970, 35, 2813.

1I Physical Methods BY J. C. TEBBY

As in previous volumes, the abbreviations PI1', PIv, Pv, efc. refer to the co-ordination number of phosphorus. Where convenient the compounds in each section are dealt with i n this order. A number of theoretical studies such as MO calculations are briefly discussed. They are placed in the sections where they are of most relevance.

1 Nuclear Magnetic Resonance Spectroscopy

The 31P chemical shifts (6,) are relative to 85% phosphoric acid.

A. Chemical Shifts and Shielding Effects.-Semi-empirical SCF-CI calculations of net charges for methyl and ethyl primary, secondary, and tertiary phosphines correlate well with experimental values of 6p.l The shielding effects of para-orientated substituents on the arylphosphine series ( l ) , (2), and (3) showed some interesting trends2 Whilst fluorine showed the strongest shielding effect of the halogens, electron-donating groups increased the shielding still further. This has been interpreted as the direct operation of a mesomeric effect increasing p,.,-d,, conjugation. Another phosphine system (4;R = Ph or OMe, Y = CI or OMe) has been ~ t u d i e d . ~ The large difference in the type of substituent makes it difficult to distinguish inductive and mesomeric effects on 6p.*

The reverse mesomeric effect (p,-p, conjugation) is believed to be very favourable in the A2-phospholen system (5).4 Compared with the corresponding A3-phospholens (6), the conjugated system ( 5 ) shows both Y and the phosphorus atom to be deshielded, and the vinyl proton is shielded. The cyclic nature of the molecule is important because the analogous R. Friedemann, W. Gruendler, and K. Issleib, Tetrahedron, 1970, 26, 2861. H. Goetz, H. Hadamik, and H. Juds, Annulen, 1970, 737, 132. A. Schmidpeter and W. Zeiss, Chem. Ber., 1971, 104, 1199. L. D. Quin, J. J. Breen, and D. K . Myers, J . Org. Chern., 1971, 36, 1297. *Throughout this chapter, where X, Y, etc. are not specified, they may be taken as representing any of a variety of groupings, e.g. halogen, alkyl, alkoxy, ptc.

a

Physical Methods

249

acyclic vinylphosphines do not show these effects. It is possible that part of the cause of the differences between the series ( 5 ) and ( 6 ) may be a shielding effect in the latter compounds (see Section 7 for discussion of stereochemical differences). Such a shielding effect (of the order Sp 2- 6 p.p.m.) has been observed for the allylic compounds (7, Y = NMe,, OPr’, or CI).s

(5)

(6)

(7)

Bulky groups tend to have a deshielding effect on SP for phosphines. Further examples have been reported.0 The effect can be considered to be opposite to the increase in electron lone-pair s-character which is produced by angular restraint,’ i.e. the bulky groups tend to increase the bond angles and increase the p-character of the electron lone-pair. The substituted trisanisylphosphines (8) show interesting differences in 8p according to the orientation of the methoxy-group in each ring.s In accordance with the mesomeric effects noted above,2 the ortlto- and para-isomers show the largest shielding of the phosphorus atom but the extra large shielding effect observed for the ovtho-isomer (where steric and inductive forces should be inducing a deshielding effect) may be due to an anisotropic effect by a methoxy-group. Further efforts have been made to produce one set of parameters which can estimate Sl. for phosphines and phosphonium salts.s The group contribution depends on the number of /land y carbon atoms, but extra shielding by phenyl and allyl, benzyl, or cyclohexyl groups has to be taken into separate account in the equation.

(8)

The chemical shifts, Sp, of substituted arylphosphonic acids (9) have been found to be linearly related to the Hammett 0 and Taft ult and 01 parameters.@ The shielding of the phosphorus nucleus increases with the electron-withdrawing properties of the substituents, which is analogous

a

A. I. Razumov, B. G. Liorber, T. V. Zykova, and I. Ya. Bambushek, Zhur. obshchei. Khim., 1970, 40, 1704. S. 0. Grim, A. W. Yankowski, S. A. Bruno, W. J. Bailey, E. F. Davidoff, and T. J. Marks, J. Chent. and Eng. Data, 1970, 15, 497. ‘Organophosphorus Chemistry’ (Specialist Periodical Report), ed. S. Trippett, The Chemical Society, London, 1971, Vol. 2, Chapter 1 I . S. 0. Grim, E. F. Davidoff, and T. J. Marks, Z . Natrrrforsch., 1971, 26b, 184. C. C. Mitsch, L. D. Freedman, and C. G . Morcland, J . Mngn. Resoric~nce,1970, 3, 446.

250

Orgnnophospiror~sChemistry

to the previously observed effect of fluorine substituents.I0 It appears therefore that electron-withdrawing groups in general tend to shield tri-, tetra-, and penta-co-ordinate phosphorus atoms, probably by increasing p,,-d, conjugation. I t is of interest that M O calculations on F3P0 indicate that P - 0 n-bonding tends to block P-F bonding and this results in an increase in the (T character as well as the creation of some T character of the P-F bond.ll When the phosphorus atom bears a group which normally shows appreciable d,-p, bonding, e.g. the oxyanion of phosphonic acids or the sulphur atom in (lo), it is possible for electron-donating groups on the aryl ring to have a deshielding effect because they reduce P=O or P=S p,-d, bonding.12 In these cases substituents which act mesonierically with the phenyl ring have the strongest effects. An effort has been made to calculate Sp non-empirically for a wide series of fluoro- and chlorophosphoryl compounds, with varied degrees of success.13

(9)

In a study of cyclic phosphoniuin salts14 it was found that, compared with acyclic compounds, a six-membered ring, as in ( l l ) , had a marked shielding effect on the phosphorus nucleus whereas a five-membered rjng had a deshielding effect. Thus relatively small deviations from tetrahedral arrangement produce a shielding effect whereas a deshielding effect is predominant when there is gross distortion of the bonds. The sensitivity of to d-orbital occupation is demonstrated by a series of alkylidenephosphoranes ( I 2).15 Shielding increases with the increase of electrondonating power of the C,-substituent (see Table I ) but decreases with increase of the electron-donating power of the P-substituents, i.c. in the order Me,P < Et,P < Pr3P.

Table 1 Phosphorane

8P lo

ll

l2 la l4

Is

Et,P=CH, - 23.6

Et,P=CHMe - 16.9

Et,P=CHEt - 14.8

E:t,P=CHPr - 14.6

‘Organophosphorus Chemistry’ (Specialist Periodical Report), ed. S. Trippett, The Chemical Society, London, 1970, Vol. 1, Chapter 11. F. Choplin and G . Kaufmann, Bull. SOC.chitti. France, 1971, 387; F. Acloquc, 0. Kahn, and A. Dniestrowski, Cotnpf. rend., 1970, 271, C, 1062; I. Absar and J. R. Van Wazer, J . Phys. Chew., 1971, 75, 1360. H . Goetz, H. Hadamik, and H. Juds, Annalen, 1970, 742, 59. A. Mueller, E. Niecke, R. Kebabcioglu, and R. Schmutzler, 2. Chent., 1970, 321. D. W. Allen and J. C. Tebby, J . Chem. SOC.( B ) , 1970, 1527. R. Kmtcr, D. Simic, and M . A. Grassbergcr, Annulen, 1970, 739, 21 1 .

Physical Methods

25 1

c

-

A series of iminophosphoranes (13) has been studied in detail.Ig The strong electron-withdrawing P-substituents were expected to encourage occupation of a second phosphorus d-orbital, i.e. overlap of the sp2 nitrogen lone electron pair with the d,, and dxs-vaorbitals of phosphorus, as shown in (14). Variation of R produced a very wide range of shifts from a 6 r value of - 28 for (13, R = H) to + 36.5 for (13, R = c-C,H,,). There c was also a decrease in the PN bond moment and an increase in v p ~ upon increasing the electron-donating power of R. Values of 6p for iminophosphoranes with phosphorus and silicon substituents and for cyclic derivatives (1 5 ) Is have also been measured. Me

c1,c

C13C

\

\-

C1--P EN, C1,C

R

/

-c

Cl-PEN-R /

C13C

(14)

(13)

Me (15)

The 31P n.m.r. parameters have been tabulated for a wide range of Prll amino-compounds 21 and Pv compounds.21 The value of aP for compounds with four P-N bonds correlates with the hybridization of the nitrogen atom,22moving to higher field in the order p 3 .c sp3 < sp2 < sp. In contrast to the phosphines, the effect of angular restraint in phosphites is to cause shielding (see Table 2).23 However, the effect is not continuous because 8 p decreases again when the restraint is severe. Possibly the increase in d-orbital occupation upon angular restraint goes through a maximum. 2op

Table 2 Phosphite SP

l8 2o 'L1 22

23

P(OEt), - 137

P(OCH,),CMe

- 91.5

/O\ P(OCH,),CH - 105

E. S. Kozlov, S. N. Gaidamaka, Yu. Ya. Borovikov, V. T. Tsyba, and A. V. Kirsanov, Zhur. obshchei Khim., 1970, 40,2549. A. Schmidpeter and H. Rossknecht, 2. Nufurforsch., 1971, 26b, 81. 0. J . Scherer and W. Gick, Chem. Ber., 1971, 104, 1490. A. Schmidpeter, H. Rossknecht, and K . Schumann, Z . Nururforsch., 1970, 25b, 1182. R. Burgada, Bull. SOC.chim. France, 1971, 136. D. Bernard and R. Burgada, Cornpi. rend., 1970, 271, C, 418. A. Schmidpeter and K. Schumann, Z . Nuturforsch., 1970, 25b, 1364. R. D. Bertrand, J. G. Verkade, D. W. White, D. Gagnaire, J. B. Robert, and J. Verrier, J . Mngn. Resonunce, 1970, 3, 494.

252

Organophosphorus Chemistry

The 31Pchemical shifts for P-F compounds have been reviewed.24 The compounds differ from most other organophosphorus compounds because 8p becomes more positive as the electronegativity of the atoms attached to phosphorus increases. The effect is at a maximum for P"l compounds. They behave normally with regard to an increase in shielding with increase in co-ordination number and therefore the PI1' compounds are the least shielded. Thus the largest negative values ( - 190 to - 250) are observed for compounds of the type YPF,. With the new value of aP of 80 for PF,, the variation of 8p with the number of fluorine atoms in Pv compounds is now shown to be fairly consistent. The value of 8p has also been reported for a series of aminohalogeno Pv c o m p ~ u n d s26. ~ ~ ~ The relative insensitivity of aP to changes in electronegativity of substituents which is observed for Pv fluoro-compounds ,* is also evident for penta-arylphosphoranes. Thus the placement of para-substituents on the phenyl rings of pentaphenylphosphorane has very little effect and 8p is + 88 f 1 p.p.m. for (16; Y = H, Me, or Cl).27 The effect on 81, of the introduction of an amino-group in the bis-biphenylenephosphorane system ( I 7) is similar to that of an alkyl group (see Table 3).28

+

Table 3 Compound

8I'

17,Y = H + 112

17,Y = Me 97

+

1 7 , Y = NH, 92

+

1 7 , Y = Bu 90

+

17,Y

=

+ 85

Ph

The leF n.m.r. spectra of the Pv compounds (18) indicate that the PAr,(OEt), group has very weak electron-withdrawing properties both inductively and mesomerically.2u This is to be contrasted with (19) where the PF, group was found to be the most strongly withdrawing group in a range of P1ll,PIv, and Pv compounds. This more recent result shows that 24

*s 28

27

2B

G . S. Reddy and R . Schmutzler, Z . Natiirforsch., 1970, 25, 1199. G . I . Drozd, M . A. Sokal'skii, 0. G . Strukov, and S. Z . Ivin, Zhrrr. obshchei Khim., 1970, 40, 2396. S. C. Peake, M . J. C. Hewson, and R . Schmutzler, J . Chern. SOC.( A ) , 1970, 2364. M . Schlosser, T. Kadibelban, and G . Steinhoff, Annalen, 1971, 743, 25. D . Hellwinkel and H. J . Wilfinger, Annalen, 1970, 742, 163. B. C. Chang, D. Z. Denney, and D. B. Denney, J. Org. Chern., 1971, 36, 998.

253

Pliysical Methods

the large CJR effect in (19) is triggered by the large inductive effect of the fluorine atoms on phosphorus. F

F

Some interesting shielding effects have been reported for the substituted A3-phospholen (20).30 The shielding effect of a P-phenyl group on the a-methyl group shifts 7hIe from 8.83 in (20, Y = :) to 9.29 p.p.m. in (21, Y = :). The oxide shows a similar effect. On the other hand, the P-benzyl group in the salts (22, R = Me) and (22, R = Ph) can achieve a conformation in which the phenyl group shields the vinyl protons so that they appear at T 4.2. The a-methylene protons of the P-chloro- and P-bromoderivatives of A3-phospholens are at unusually low field, and their equivalence suggests that there is loss of configurational integrity at phosphorus.gl Cooling or dilution in hexane raises the chemical shift and produces a multiplet signal. These results are consistent with a rapid intermolecular halogen exchange reaction.

Y

The 'H chemical shifts of the P-H group have been tabulated for 150 Like many other heteroatom-bound protons, the chemical shift range is large (7 0 -12 p.p.m.). In this case shielding of the proton increases with decrease in co-ordination number at phosphorus. The 30

31

L. D. Quin and T. P. Barkett, J . Anter. Cheni. SOC.,1970, 92, 4303. D. K. Myers and L. D. Quin, J . Org. Chem., 1971, 36, 1285. D. Houalla, R. Marty, and R. Wolf, 2. Nntrrrforsch., 1970, 25b, 451.

Organophosphorus Chemistry

2 54

presence of P-aryl groups causes deshielding of the proton, as does its attachment to a phosphonium centre.33 There is an upfield shift upon dilution (AT 0.2 p.p.m.) which is intermediate between that (AT 0.05 p.p.m.) for SiH and that (AT 0.5 p.p.m.) for SH. This trend also parallels the hydrogen-bonding abilities of the groups. 31P N.m.r. studies are reported on the triethylphosphine 34 and trisdimethylaminophosphine 35 complexes with boron halides, and triethylphosphine complexes with aluminium chloride.3s A correlation of aP with the number of phosphorus ligands in metal carbonyl complexes has led to a qualitative rationalization of 8p in terms of u- and ~ b o n d i n g . ~ '

B. Studies of Equilibria and Reactions.-N.m.r.

spectroscopy is being increasingly employed to study the mode and course of reactions. Thus 31P n.m.r. has been used to unravel the mechanism of the reaction of phosphorus trichloride and ammonium chloride to give p h o ~ p h a z e n e s , ~ ~ and to follow the kinetics of alcoholysis of phosphoramidite~.~~ Its use in the study of the interaction of nucleotides and enzymes has obtained valuable information on binding sites and conformations 40 and work on the line-widths of the 31Presonance has enabled the calculation of dissociation rate-constants and activation energies to be p e r f o ~ r n e d . ~ ~ lH N.m.r. spectroscopy has been used to identify phosphorus pesticides 4 2 but the complexity of the spectra would make it difficult to analyse mixtures. 31P N.m.r. spectroscopy is better adapted to this task, especially when the compounds differ in the groups immediately attached to phosphorus. Thus 81, values of the commonly used pesticides fall into eight well-separated regions (see Table 4).43 It is also possible to estimate the chain length of linear polyphosphates using 31P n.m.r. The P,, P,, and P6-80 middle 22 p.p.ni. respectively, whilst phosphate groups have aP + 19, + 21, and 5, + 8, + 9 and the PZp3, P,, Po, and P,o end-groups give peaks at + 10 p.p.m. re~pectively.~~ The 6p values also depend upon the p H of the solution. This method has also been used for the direct determination of

+

33

s4 56

s6 s7

s*

40

" 42

'' 44

+

J. R. Cortield, M . J . P. Hargcr, R. K . Oram, D. J . H . Smith, and S. Trippctt, C ' h t t i . Corntn., 1970, 1350. G . Jugie, J . P. Laussac, and J. P. Laurent, B i d . SOC.chim. Fruticc.. 1970, 2542. G . Jugie, J. P. Laussac, and J . P. Laurent, J . Inorg. Nuclear Chem., 1970, 32, 3455. W. H. N. Vriezen and F. Jellinek, Rec. Trm. chim., 1970, 89, 1306. R. Mathieu, M. Lenzi, and R. Poilblanc, Inorg. Chem., 1970, 9, 2030. J. Emsley and P. B. Udy, J . Chem. Soc. ( A ) , 1970, 3025. E. E. Nifant'ev, N. L. Ivanova, and A. A. Borisenko, Zhur. obshchei Khirn.,1970,40, 1420. D. H. Meadows, G. C. K . Roberts, and 0. Jardetsky, J . Mol. Bid., 1969, 45, 491. G . C. Y . Lee and S. I. Chan, Biochetn. Biophys. Res. Cotnm., 1971, 43, 142. L. H. Keith, A. W. Garrison, and A. L. Alford, J . Assoc. Offir. Atrn1J.t. Chetnists, 1968, 51, 1063; H . Babab, W. Herbert, and M . C . Goldberg, AnnlJIt. Chint. Actn, 1968, 41, 259; L. H. Keith and A. L. Alford, ihid., 1969, 44, 447; L. H . Keith and A . L. Alford, J . Assoc. Ofic . Anolyt. Chemists, 1970. 53, 1018. R. T. Ross and F. J . Biros, Annlyf. Chittt. Acto. 1970, 52, 139. M . Kawabe, 0. Ohashi, and I. Yamaguchi, Blrll. Chern. Soc. Jrrprirl, 1970. 43, 3705.

Physical Methods

255

Table 4 Class of compound SP

Class of compound

Sr Class of compound SP

phosphates 6 + 3

phosphoramidates - 8

phosphoramidothioates -64+7 phosp horot ri t hioates - 118

phosphonates - 18

phosphorothioates -64+_3

phosphonothioates

phosphorodithioates

- 85

-95k3

phosphites - 140

linear phosphates in biological extracts,46and to distinguish phosphonates and phosphates occurring in lipid fractions.46 Metaphosphates gave separate signals with and without the addition of magnesium The stereospecific nature of the dehydration of 2-phosphoglycerate to give (23) was established after the assignment of the chemical shifts of HA and HB had been d e t e ~ m i n e d . ~ ~

A fluxional amido-salt (24), in which the y-nitrogen atom acts as an internal nucleophile, has been identified by variable-temperature n.m.r. s p e c t r o s ~ o p y . ~At ~ - 63 "C two methyl signals are observed, one a singlet, one a doublet (J = 11 Hz) whereas at + 60 "C there is only one signal, a doublet with J = 5.5 Hz (the average of the low-temperature coupling constants). The solvent extraction of organophosphorus compounds has also been studied by 31Pand 'H n.m.r.4e

C. Pseudorotation.-An alternative intramolecular exchange process to Berry pseudorotation has been suggested, which also occurs with conservation of angular momentum.60 It has been called a 'turnstile-rotation process' because it involves the rotation of an apical-radial pair of ligands 4.5

T. Glonek, M. Lunde, M. Mudgett, and T. C . Myers, Arch. Biochem. Biophys., 1971,

40

T. Glonek, T. 0. Henderson, R. L. Hilderbrand, and T. C. Myers, Science, 1970, 169,

47

M. Cohn, J. E. Pearson, E. L. O'Connell, and I. A. Rose, J . Amer. Chem. SOC.,1970,

142, 508.

192. 92, 4095. 48

T. Winkler, W. Von-Philipsborn. J. Stroh, W. Silhau, and E. Zbiral, Chem. Comm.,

49

A. M. Rozen, P. M . Borodin, U. I. Mitchenko, and Z . I. Nikolotova, Radiokhimiya, 1970, 12, 510. I. Ugi, D. Marquarding, H . Klusacek, G . Gokel, P. Gillespie, and F. Ramirez, Angeiv. Chrm. Inttmwt. Edn., 1970, 9, 725.

1970, 1645. 60

256

Organophosphorits Chemistry

in the opposite direction to a rotation of the remaining three ligands. The result is the same as that of Berry pseudorotation, i.e. interchange of apical and radial pairs of ligands. The turnstile rotation is believed to be the cause of the rapid positional exchange of the ligands about the phosphorus atom in (25); the exchange was indicated by its 'H and 19Fn.ni.r. spectra. The barrier to Berry pseudorotation and the turnstile rotation could be different for molecules such as dimethyl trifluorophosphorane ; however, it is claimed that the exchange process is intermolecular and has a very low activation energy,51a similar to that observed for difluorotrimethylphosphorane (26, R = Me). Details are reported for this latter compound. The spectrum was concentration dependent (second-order in phosphorane) and whereas PCH coupling was maintained upon raising the temperature or concentration, the FPCH coupling was lost. Also, an estimate of the coalescence temperature for the fluorine resonances (made from Jpp i n the instantaneous structure) agreed with that observed. More recently, the variable-temperature spectrum of (26, R = Me) was studied in a wide range of In tetramethylsilane the activation energy was 15 f 2 kcal mol-l, indicative of an intraniolecular exchange process in this solvent. Also, at high temperature J F ~= I 4(2J~,11 J I , - ~ I where I) F, = apical fluorine and F, = radial fluorine.

+

F

The orientation assumed by bulky groups is of great interest since i t would assist the assessment of steric effects in Pv molecules. The spectra of some t-butylfluorophosphoranes have been d e t e r ~ i n e d .The ~ ~ spectrum of t-butyltetrafluorophosphorane was unchanged down to - 100 " C , indicating rapid positional exchange (cf. PhPF4).10 Like other dialkyltrifluorophosphoranes, the t-butyl compound (26, R = But') exhibits two types of fluorine atoms in its 19F 1i.m.r. spectrum, with chemical shifts and coupling constants characteristic of one radial and two apical fluorine atoms. The character of the n.m.r. parameters of the tributyl derivatives also supports the presence of two apical fluorine atoms, which shows that 51

52

( a ) T. A . Furtsch, D. S. Dierdorf, and A . H . Cowley, J . Artrer. Cherir. S'oc., 1970, 92, 5759; ( h ) H . Dreeskamp and K . Hitdenbrand, Z . Nofurforsch., 1971, 26b, 269. M . Fild and R. Schmutzler, J . Cherji. SOC.( A ) , 1970, 2359.

any steric compression between the three t-butyl groups is not sufficient to displace fluorine from its apical orientation. Dynamic processes in fluorophosphoranes have been reviewed.53 Variable-temperature lH n.m.r. spectroscopy on the oxyphosphoranes (27) and (28) has shown that a t-butyl group has a thermodynamic preference for a radial o r i e n t a t i ~ n .Thus ~ ~ whereas pseudorotation between the isomers (28a) and (28b), which maintain a radial t-butyl group, is observed, the steric repulsion between the t-butyl group and the or-phenyl group in (27) is sufficient to destabilize the isomer in which these groups are crowded together, and consequently no pseudorotation is observed. Had it been energetically favourable for the t-butyl group to occupy an apical orientation, pseudorotation would still have been observed. Me

Ph

Ph

McCO

H OMC

* OMe

OMe

The possibility that small rings may be able to increase rates of pseudorotation was advanced in Volume 1 of these Reports.lO Recent results add weight to this suggestion. Thus fast pseudorotation is reported for (29) G 5 and (30).66As in the previous examples, the small rings haveidenticalatoms bound to phosphorus and two other atoms or groups are identical, both of which encourage competition for the electronically preferred orientations. The pseudorotation process for (30) which maintains the phenyl group in a radial orientation has a very low barrier. Above - 5 1 "C pseudorotation uia (31) also becomes allowed and above 30 "C pseudorotation vicr (32), which has the ring spanning both radial positions, is possible. In this case the attainment of axial orientations for the two electronegative ethoxygroups and a radial orientation for the phenyl group probably offsets some of the ring strain in (32). Similar observations were made on its isomer (33). The room-temperature lQFn.m.r. spectrum of (34) contains a doublet, indicating equivalence of the trifluoromethyl groups. This signal collapses upon cooling the sample, to give a spectrum corresponding to apical and radial trifluoronlethyl groups.57 The 'H n.m.r. spectrum is unchanged upon cooling, which supports the suggestion of formation of the structure shown in (34). 63

b4 66 68

67

S. C. Peake and R. Schmutzier. Colloq. l u r . Cent. Nat. Rech. Sci., 1970, 101. A. P. Stewart and S. Trippett, Chem. Cotnni., 1970, 1279. G. 0. Doak and R. Schmutzler, J . Cheni. SOC.( A ) , 1971, 1295. D. Z. Denney, D. W. White, and D. B. Denney, J . Amer. Chem. Sac., 1971, 93, 2066. R. G. Cavell and R. D. Leary, Chem. Cumtrz., 1970, 1520.

258

Organophosphorus Chemistry

OEt

Ph

(30)

(31)

OE t .I.

I

(32)

(33)

(34)

36Cl Nuclear quadrupole resonance (n.q.r.) studies s8 on PhPCI, and Ph,PC13 indicated non-equivalence of the chlorine atoms. However, a more recent report6@states that the spectra of these compounds and PCI, all contain two signals corresponding to apical and radial chlorine atoms and that replacement of chlorine by phenyl occurs in the radial position. D. Restricted Rotation.-A study on solvent and stereochemical effects on the restricted rotation of the stabilized ylides (35) has shown 6o that although the cisoid ( 2 ) conformation (35a) is generally predominant there is an increase in the amount of the transoid (E) conformation (35b) as the size

(35a)

(35W

of the ester alkyl group increases. It also increases as the polarity of the solvent increases, especially if the solvent has hydrogen-bonding properties. When both effects are combined, e.g. (35, R = t-butyl) in methanolic solution, the spectrum shows a predominance of the transoid conformer. The results were rationalized in terms of increased solvation of the oxyanion. The absence of a rotational process for the y-conjugated ester group in (36) was confirmed by the lack of variable-temperature spectra for (37).61 That this is due to lack of rotation is supported by the low carbonyl frequency of the y-methoxycarbonyl group and the strong r,t~ 69

uo

M. Kaplansky, R. Clipsham, and M. A. Whitehead, J. Chem. SOC.( A ) , 1969, 584. V. I. Svergun, V. G. Rozinov, E. F. Grechkin, V. G. Timokhin, Yu. K. Maksyutin, and G. K. Semin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 1918. J. P. Snyder, Tetrahedron Letters, 1971, 215. N. E. Waite, J. C. Tebby, R. S. Ward, M. A . Shaw, and D. H. Williams, J. Chem.

SOC. (C), 1971, 1620.

Physical Methods

259

conjugational effects on the stereocheniistry in the crystal (see Section 7 of this chapter). Y

The extent of restricted rotation about the amide band of (38) was used to compare the electron-withdrawing process of phosphonium salts (38, Y = alkyl) and chalcogenides (38, Y = 0 or S) with the more conventional electron-withdrawing groups.sz These phosphorus groups were found to exert a - M effect comparable with that of a nitro-group. Restricted rotation has been observed in tris-o-tolylphosphine sulphide and selenide (39).'j3 The spectrum of the selenide shows two methyl environments in the ratio 2 : 1 at 30°C but the methyl signals of the sulphide resolved to this pattern only upon cooling the sample. The corresponding oxide and the parent phosphine showed only one methyl environment down to - 60 "C. X-Ray diffraction of the selenide showed that the methyl group on one aryl group is directly behind the phosphorus atom in the crystal, as shown in (39).

M'e (38)

(39)

E. Inversion, Non-equivalence, and Configuration.-The inversion of phosphines is much slower than that of amines, and optical isomers of dissymetric phosphines can be isolated. Studies of the factors which affect the rates of inversion are advancing our knowledge of inversion processes in general. Delocalization of the lone electron pair lowers the barrier to inversion, and one way of achieving this is to have a silicon atom bonded directly to the inversion centre, as in (40).64 The coalescence temperature of the two methyl signals from the isopropyl group showed A c t to be 18.9 kcal mo1-l. The suggestion that pn-dn conjugation is the dominant effect is supported by the slightly higher barrier (AG: 21.4 kcal mol-l) to 82

84

G. P. Schiemenz and G. Stein, Tetrahedron, 1970, 24, 2007. R. A. Shaw, M . Woods, T. S. Cameron, and B. Dahlen, Chem. and Itid., 1971, 151. R. D. Baechler and K. Mislow, J . Amer. Chern. SOC.,1970, 92, 4758.

260

Orgarzophosphoriis Chemistry

inversion for the corresponding germanium derivative (which involves the less effective 3p-4d .rr-orbital overlap). The lower electronegativity and absence of lone electron pairs also makes silicon more effective at lowering the inversion barrier than sulphur or phosphorus.

The non-equivalence of two atoms or groups in the close proximity of an asymmetric centre may vary with concentration, temperature, and solvent. When the asymmetry is provided by a PI'' atom, loss of nonequivalence may be due to (a) inversion at phosphorus, as above,G4 ( b ) conformational changes, e.g. the fluorine atoms in (41),G5or (c) an intermolecular exchange process at phosphorus. Some examples of this latter type have recently been uncovered in which the exchanging atom is chlorine or bromine. Thus the methyl signals of the isopropyl group in (42,Hal = CI) merge at 50 "C whereas in the corresponding P-F conipound (42, Hal = F) the non-equivalence persists on raising the temperature.ss There was no doubling of the N-methyl groups at low temperatures, which shows that there is free rotation about the P-N bond. When the asymmetric centre is on a carbon atom it is possible to observe nonequivalence of P-substituents, e.g. in (43).67

The non-equivalence of the ester protons in the monomethyl- and monophenyl-phosphinic ester function, as in (44, Ch = chalkogen), has been studied.68 Compounds of type (45) have some interesting stereochemistry. They are prepared from racemic secondary butyl alcohol, and the presence of three signals in the 31P n.m.r. spectrum confirms that the phosphorus atom is the centre of pseudo-asymmetry.G8 A 1 : 2 : 1 triplet is observed which is attributed to the presence of equal amounts of two rnem forms, (45) and (46),which have different values of 8p (outer peaks), and two racemic forms, (47)and (48),which have identical values of 8p (central peak). e6

e7

du

H. Goldwhite and D. G . Rowsell, J . Mol. Spectroscopy, 1968, 27, 364. J. E. Bissey, H. Goldwhite, and D. G . Rowsell, Org. Mugn. Resonatice, 1970, 2 , 81. R. Fields, R. N. Haszeldine, and J. Kirman, J . Chem. Soc. (C), 1970, 197. R. Marty, D. Houalla, R. Wolf, and J . Riess, Org. Magn. Resonance, 1970, 2, 141.

Pliysical M e tliods

26 I

c 11

When a second asymmetric centre is present in the molecule in addition to an asymmetric phosphorus centre, diastereomers are produced whose n.ni.r. parameters may be used to identify the configuration. The second asymmetric group may be an inherent part of the molecule, as in (49), or may be introduced in the alcoholic part of an ester or the counter-ion of a salt. Thus the POCH signals of the ( R ) p isomer in (49) are downfield by 2--3 Hz from those of the (S)p the doublet methyl signal of the isopropyl group of the phenylphosphinates (50) is downfield for the ( R ) l , e~inier,~O and in the phenylethylamine salts of thiophosphonates ( 5 1 ) the degree of non-equivalence of the P-methyl signal is related to its absolute c~nfiguration.~’ 0 II P - - - C6H1

”’/ \o JPCH21< 0 0

(49)

(50)

Mcnthyl

S II Mc-P-OR I + 0- N H , C H P h M e (51)

N.m.r. spectroscopy has played an important part in determining the stereochemistry of the 1,3-dioxaphosphorinanes (52). The presence of the saturated six-membered ring means that there are usually conformational effects to be unravelled before configurational assignments can be made. The chair conformation is generally d ~ m i n a n t . ’ Phosphorus ~ substituents which exhibit shielding effects show that in many PIr1phosphorinanes this has been used to establish substituent occupies an axial position 7 2 and L(the equatorial conformation of a t-butyl substituent at C(5).’, Even in PIv derivatives the isomer possessing the bulkiest P-substituent in an axial K . E. DcBruin and M. J . Jacobs, Clret)i. Con:t?i.,1971, 59. W. B. Farnham, R . K . Murray, and K . Mislow, Chem. Comtn., 1971, 146. M . Mikolajczyk, M. Para, A . Ejchart, and J. Jurczak, Cheni. Cotiim.. 1970, 654. i2 W. G. Bentrude and K . C. Yee, Tetmhedroti Letters, 1970, 3999; M . Haemers, I<. Ottinger, J . Reisse, and D . Zimmermann, ihid., 1971, 461. 73n W. G . Bentrude and J . H . Hargis, J . Atiier. Chem. SOC.,1970, 92, 7136; W. G . Bentrudc, K . C. Yec, R. D. Bertrand, and D. M . Grant, ibid., 1971, 93, 797. HI

70

262

0rganophospho r us Chemistry

orientation is formed prefer en ti all^.^^ Broadening of the signals with rise in temperature for the P-halogeno-compounds (52, Y = C1 or Br) has been attributed to intermolecular halogen ex~hange.'~ Y

F. Spin-Spin Coupling.- -(i) Jpp arid J p g ~ . The coupling constant between directly bonded tetrahedrally and octahedrally bonded phosphorus atoms, e.g. P, and Pp in (53), was shown to be very large and po~itive.'~ The signs of the coupling constants were obtained from their INDOR spectra. These were obtained manually, by systematically increasing the decoupling frequency in the region of phosphorus resonances by 20 H z increments whilst observing the resonance of the radial fluorine atom. When the nucleus Pp was irradiated at its exact resonance frequency, the decoupled regions were spaced apart by 720 +_ 20 (lJpp) and 180 k 20 Hz (2Jr,v; known to be negative in sign). The signs were opposite since the lowfield P and high-field F resonances were connected, and therefore lJP1.is positive. This is by far the largest magnitude so far recorded. This result fits in with previous data in that negative constants are only observed if one or both phosphorus atoms are trico-ordinated. A further example of a very low value for ' J I ' p (22.5 Hz) was observed for (54).77 Me Me, I ,Me

'i" (54)

FP

(53) The value of J P N P ,92.5 Hz for ( 5 3 , is intermediate between those of difluoro- and monofluoro-PI" The magnitude is 74 76

76

77

78

C. L. Bodkin and P. Simpson, J. Chern. Sac. ( B ) , 1971, 1136. D. W. White, R. D. Bertrand, G. K. McEwen, and J. G. Verkade, J. Amer. Chem. Soc., 1970,92, 7125. C. W. Schultz and R. W. Rudolph, J. Arner. Chem. Soc., 1971, 93, 1898. J. Koketsu, M. Okamura, Y. Ishii, K. Goto, and S. Shimuzo, Znorg. Nuclear Chem. Letters, 1971, 7 , 15. J. F. Nixon and B. Wilkins, 2. Naturforsch., 1970, 25b, 649.

Physical Met kods

263

considerably lower when the phosphorus atoms are tetraco-~rdinated.~~ Studies on the spin-spin coupling constant between directly bonded Si and Prrl atoms indicate that 'Jpsi is 42.2 ('Kpsi is - 43.7) for P(SiH3)3;80 ' J ~ Sis, ~of a much larger magnitude, being 443 Hz for Me3117SnPH2and 463 Hz for Me3119SnPH2.81Measurements of Jppt in phosphine-platinum complexes have been used to determine the order of the trans influence of the ligands.82

+

It (ii) JPF. A large number of data now exist on this coupling is generally very large (often over 1000 Hz) for a wide range of compounds of P I 1 , P'v,84and P v e 5 co-ordination. In a recent report on some Pvl compounds, J p l ? was rather more variable than usual. (iii) Jp(.. ~ J ~ IisIin IC the range 0-26 Hz for compounds in which this carbon atom is sp2 hybridized*7 and a little higher for sp3 carbons, e.g. (56) and (57).74 A change in configuration also alters 8p and the coupling constants, i.e. J p c 42.8 Hz, 8p - 185.2 p.p.m. for (56) and Jpc 32.2 Hz, 8r - 161.6 p.p.m. for (57). lJp(: is + 56.5 for Me,P+ and 85.1-1 13 Hz for heteroaromatic derivatives such as (58, Y = O).87 The rise is consistent with a dominant contact term which depends on the s-character of the bonds. This is supported by the further increase for Me3PF2 ('JpC: + 128 Hz), where the three radial phosphorus orbitals have nearly sp2 character.s3 'Jpc increases further still for MePF,- to + 1262 Hz, in accordance with concentration of s-character towards the electropositive groups. All the PC coupling constants have been determined for the furanyl and thienyl phosphorus series (58, Y = 0 or S). 3Jp1~~c correlates quite well with k 3 J p = of trivinylphosphine. On the other hand, although values of SlSc roughly correspond to the 'H shifts, their magnitude is several times greater. 7ep86

(57)

The coupling constant ' J ~ Hfor phosphine-borane adducts (355-385 Hz) is intermediate between those of Prrrand PIv compounds.88 This coupling constant is not much higher for the phosphinimine (59)17

(iv)

lJp~.

H. W. Roesky, 2. Naturforsch., 1970, 25b, 777. K. D . Crosbie and G. M. Sheldrick, Mol. Phys., 1971, 20, 317. A. D. Norman, J . Orgatiometallic Chetn., 1971, 28, 81. F. H. Allen, A. Pidcock, and C. R. Waterhouse, J . Chem. SOC.( A ) , 1970, 2087. H. Dreeskamp, C. Schumann, and R. Schmutzler, C h e w . Comm., 1970, 671. L. F. Centofanti and R . W. Parry, Inorg. Chent., 1970, 9, 2709. G. I. Drozd, M. A. Sokal'skii, and S. 2. Ivin, Zhrrr. obshchei Khim., 1970, 40, 502. J . F. Nixon and J . R. Swain, J . Chem. Sue. ( A ) , 1970, 2075. H . J . Jakobsen and 0. Manscher, Acta Chetn. Scand., 1971, 25, 680. J. Davis, J . E. Drake, and N. Goddard, J . Chem. Soc. ( A ) , 1970, 2962.

2 64

Ol-~arrophosphorlrsClieniistry

and for cyclic phosphine hydrobroniides.33 The presence of a P-halogen group increases the magnitude, as expected, and I J ~ His 772 Hz for (60).84 This overlaps with the lower end of the range of Pv coupling constants, e.g. lJp~1 768 Hz for (61).89 Likewise ‘Jp11 for the Pv and Pvl compounds 86 overlap around 1000 Hz.

J ~ ( ~ , I I The . influence of the orientation of the lone electron pair on is well established. It is found that the dependence is similar for P-alkyl and P-aryl compound^.^^ This study also revealed that homoallylic coupling ( . l ~ ( * l > ( ~ I xthrough ) a P1”atom is also affected by the lone electron pair orientation, being larger when the protons and the lone electron pair are on the same side of the ring, as in (62). The geminal coupling constants, J l , c y ~ r A and JI>C-Qfor (63, Hal = F) are of the same sign (13.5 and 4.2 Hz) when there is free rotation about the P-N bond,6s whereas in the chloride (63, Hal = CI) rotation about the P-N bond is more restricted and the coupling constants are of opposite sign (26 and 3 Hz). (0)

2 J I m ( l ~ ~

H

The very large geminal coupling constant involving sp2 carbon atoms which is observed in compounds of the type (64) has been discussed previously (ref. 10, p. 298). The presence of a P-Cl group had its usual effect and increased the coupling constant. Thus Jpc-11 for (64; Y = CI) is 46.5 H z . ~ ‘The large magnitude of these interactions may also be connected with pn-pn conjugation, a suggestion which is supported by the large magnitude of this coupling in the heteroaromatic derivatives (65) g 1 and (66).e2 These geminal couplings are to be contrasted with those of vinyldialkylphosphines which are of a very low magnitude, 1---2 H z , ~(cJ~ 80

00

611 92

93

M. Sanchez, J. Ferekh, J . F. Brazier, A. Munoz, and R . Wolf, Roczniki Chem., 1971, 45, 131. J. P. Albrand, D . Gagnaire, M. Picard, and J . B. Robert, Tetrahedron Letters, 1970, 4593. T. H. Chan and L. T. L. Wong, Canad. J . Chern., 1971, 49, 530. F. Mathey and R. Mankowski-Favelier, Bull. Soc. chitn. France, 1970, 4433. G . Borkznt and W. Drenth, Rec. Trot.. chinr., 1970, 89, 1057.

Physical Methods

265

+

J P C ~ I I 1 1.74 Hz for trivinylphosphine). These fascinating changes were also discussed in Volume 2 of these report^.^

Y

I’ll

(6.1)

(65)

The sign of J f c ,for ~ ~I”” compounds of the type (67), although ncgative when Y i s alkyl, dimethylamino, or methoxy, appears to be positive when Y is fluorine or c h l ~ r i n e .However, ~~ there is little difference in the magnitude of these constants. The spectra of the corresponding vinyl compounds (68) are also reported.95 In this case the magnitude of Jp( 11 for the dichloroand dianiino-derivatives is very large (41.6 and 30.9 Hz respectively), which is well above the usual range of 5 --25 Hz (ref. 7, p. 254).

Accurate values of J P , - H for methylenephosphoranes are difficult to obtain because tvctns-ylidation tends to decouple the nuclei. The spectra of the ylides (69) and (70) indicate Jp(‘11to be 22 and 12.7 Hz respectively,06 which is consistent with the .rp2character of the carbon bonds (ref. 10, p. 296). Similarly, Jp(.rI in the cyclic salts (71) is also

+

Some interesting Pv compounds have been prepared. The value of 13 Hz for (72) gg and 11 Hz for (73) but increases to the range 15 -20 Hz for the fluorophosphoranes ( 2 6 ) and cyclic oxyphosphoranes such as (29).55

Jp(’1.1is

94

1’. N. Timofeeva, U . L. Kleirnan, and B. I . Ionin, Zhrtr. obshchei Khin!., 1970, 40, 1046.

m no

RN

T. N . Timofeeva, €3. V. Semakov, and B. I. Ionin, Zhrtr. obshchei Khim., 1970, 40, 1169. W. Malisch, D. Rankin, and H. Schmidbaur, Chem. Ber., 1971, 104, 145. M . L. Filleux-Blanchard, M. Simalty, M. Berry, H . Chahine, and H . M . Mebazau, Brill. SOC.chiin. Frorice, 1970, 3549. ’r.J. K a t ~and E. W. Turnhloni, J . A m v - . C/rc.ui. Sot.., 1970, 92, 6701.

266

Urganophosphorw Chemistry HH

OE t (73)

The vicinal coupling constants in phosphines depend not only on the angles subtended by the three bonds but also on the orientation of the lone electron pair. Change in the former is limited in cyclic phosphines such as (20, Y = :) and (21, Y = :) and the effect of the orientation of the lone electron pair can be distinguished. The PCCH, coupling is much larger when the methyl group and lone electron pair are cis. Thus in (20, Y = :) and the corresponding P-methyl compound, J ~ c c ' His, 17-18 Hz, whereas J p c , ; ~is , 10 Hz for the phosphines with the other c o n f i g ~ r a t i o n . ~ ~ The range of 3Jpn is 14-20 Hz for the tetraco-ordinate PIv cyclic derivatives (20 and 21, Y = Ch or R) and 15-24 Hz for the PIv-ethyl series of compounds (67) in which there are quite large changes in the environment of the phosphorus atom, e.g. from (67, Y = F) to (67, Y = alkyl). The magnitude of this parameter is slightly larger for the t-butylthiophosphoryl halides (74).88 When the vicinal coupling involves a Pv atom the magnitude of coupling is similar to PIv compounds, e.g. 3 J p ~= 16 Hz for (30) and 19 Hz for (73).66 The rapid pseudorotation reported for these compounds means that these values are the average of coupling through apical and radial bonds. S

II McSC-PXY (74)

Some high vicinal coupling constants have been reported for vinyl systems. The trans PC=CH coupling constants for (68, Y = NMe,) and (68, Y = CI) are 57.0 and 77.6 Hz respectively. This is well above the usual range (28-51 Hz).l09 loo The cis PC=CH coupling constants of (68, Y = NMe, or C1) were also high (28.7 and 35 Hz respectively) thus maintaining the usual ratio between the cis and trans constants. More n.m.r. studies on the trifuranylphosphine system are reported.lol The couplings to the ring protons are all positive whether the phosphorus atom is bound to the a or position of the furan ring.lo2 However, longrange coupling to the C(5)-methyl group of the series (75) is positive for the phosphine but negative for the PIv compounds. 99

loo

Io1 lo*

G. Huegele and W. Kuchen, Chem. Ber., 1970, 103, 2 8 8 5 . P. Taw and H. Weitkamp, Tetrahedron, 1970, 26, 5529. F. Taddei and P. Vivarelli, Org. Magn. Resonance, 1970, 2 , 319. H . J . Jakobsen and M. Begtrup, J . Mol. Spertroscopy, 1970, 35, 158; H . J. Jakobscn, ibid., 1971, 38, 243.

Physical Methods

267

The thiazole ring is not renowned for its ability to transmit coupling effects, and therefore the report that the phosphonium derivative (76) exhibits long-range coupling of the magnitude 5 J p ~ 4e Hz and 6 J p ~ 3e Hz is quite surprising.1o3 If the structure is correct, then presumably throughspace coupling to the C(4)-methyl and coupling transmitted through the lone electron pairs on sulphur to the C(3)-methyl could be invoked. hl e N 4

( u i ) J,ioc,,ri, JpIVcnII,and J,i.vr'fi. The variation of J ~ O C with H dihedral angle has been used by many workers to estimate the stereochemistry of phosphorus heterocycles such as the dioxapho~phorinanes.~~-~~ A comparison of the angular dependence of J P O ( ~in H PI" and PIv compounds has been made, based on the cyclic phosphite (77, Y = :) and the corresponding phosphate and thiophosphate (77, Y = Ch), for which the dihedral angles can be fairly accurately estimated.lo4 The coupling constant of the PVcompounds rose steadily from 0 Hz at 60" to 24 Hz at 180" whereas in the phosphites J p o c ~ was l ~ at its lowest magnitude (0 Hz) at 120°, rising to a maximum of 16 H z at 180". The effect of the nature of the phosphorus atom on PVOCH coupling in the acyclic compound (78) has been studied in detail.Io5 I t is found that the coupling increases with the number of electronegative substituents, the largest magnitude being 17.2 Hz for (78; Ch = 0, X = Y = CI). A correlation of a2 (a measure of s-character which is obtained from 'Jp(; = 500d Hz) withJpoc.Ilshowed that the increase is due to increased s-character. The coupling constants of the chalcogenides of (78) increased with the mass of the chalcogenide, i.e. 0 < S < Se. Since little change of s-character is expected in this series, a variation in d,,-pn bonding may be an important factor. Jt is interesting to note that the range of J L , O ( ' ~ for l freely rotating POCH groups is quite similar for P'" and PIv compounds, i.e. about 7-14 Hz.

In8

F. Zbiral, Tetrahedron Letters, 1970. 5107. I). W. White and J. G . Verkade, J . Magti. R~.coiiaiirc,1970, 3, 1 1 1. M. Kainosho, J . Phys. Chein., 1970, 74, 2853.

268

Orgatiuphosphorirs Chemistry

Protonation studies of diphenylphosphinic esters and amides show that i .crcascc upon protonation of the esters but that J ~ N ( -decreases H up,,ri protonation of the amides.lo6 Values of JPN(.II have been tabulated for a number of P I ' ' compounds.20~ 21 The cyclic aminophosphine (79) has all four J P S ( - Hconstants with the same sign, probably positive.lo7 Attachment of the proton to an sp2 carbon atom, as in (SO), does not enhance JpN('I[; in fact the reverse occurs.1o8 The PNPH coupling constant, which is 3-4 Hz for the acyclic phosphinimine (SI), is quadrupled (13-14 Hz) when the amino-groups are included in a small ring, as in (82).19

JIl,,

0

II

( E t O), I'

c 11

t1 I

N H C =C Ph

( M e,N )

I1 P H =N 1% 'I

I

hl e

(82) G. Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies.-lH and 31Prelaxation studies of some arylphosphines indicate that both dipolar and spin-rotation interactions contribute to the 31P relaxation in PhzPCl and PhPCl,, the spin-rotation interaction being more important at high temperature^.^^^ As expected, spin-rotation relaxation (estimated to occur only above 400 " C )was not observed for Ph,P. The phenyl rotation must be restricted, for although a cogwheel concerted rotation is energetically possible, such perfectly geared rotation of rings is improbable. Spin relaxation times have also been used to study enzyme-inhibitor interactions.l1° The shifts produced by the addition of a paramagnetic complex have been used in the assignment of the aromatic protons in (83).11' Several 35Cc1 nuclear quadrupole resonance (n.q.r.) studies have been carried out on chlorophosphorus c o m p o ~ n d s5.9~ ~The ~ frequencies observed for phenyldichlorophosphine are similar to those of phosphorus lo6 lo7 Ion loo

P. Haake and I. Koizumi, Tetrahedron Letters, 1970, 4849. J. Devillers, J. Roussel, R. Bugada, and J. Navech, Buff. SOC.chitn. France, 1971, 676. A. Zwierzak and A. Koziara, Tetrahedron, 1970, 26, 3527. S. J. Seymour and J. Jonas, J. Chetn. Phys., 1971, 54, 487.

B. D. Sykes,J. Atner. C'hetn. Soc., 1969,91, 949; B. D. Sykes, P. G. Schmidt,andG. R. Start, J . Biof. Chctn., 1970, 245, 1180. J. C. Kotz and R. J. Humphrey, Znorg. Nuclear Chem. Letters, 1970, 6 , 827.

Physical Methods

269

trichloride. The p-chlorophenyldichlorophosphine (84) has an absorption frequency (35.018 MHz) corresponding to the chlorine atom on the phenyl ring, which indicates that the PClz group is electron-withdrawing.ll2 The variable-temperature n.q.r. spectrum of the phosphinimine (85) shows a change in the frequencies of the absorptions at about - 188 "C. This is probably related to a phase transition in which the lattice deformation alters N-S p,-d, bonding.l13

2 Electron Spin Resonance Spectroscopy The e.s.r. spectra of stable phosphorin radicals have been reviewed.l14 Radical anions may be formed from phosphines with or without P-C cleavage. The PIv radical (86) is easier to prepare than the nitrogen analogue. It has a spectrum in which the coupling to phosphorus is strongly temperature dependent, probably due to a variation of the geometry of the lone electron pair.l15 The n-spin populations indicate that the Me$ group is electron-attracting, probably due to p,-d, bonding. The spectrum of the radical (87), which is prepared from tris-a-naphthylphosphine, has also been described.l16

The e.s.r. spectrum of the phosphonium radical (88, Y = H) resembles that of Ph&H except that the splitting produced by the phosphorus atom is over three times that produced by the methine proton.l17 The spectrum of (88, Y = COMe) was also determined. The formation of the triradical 115 113

118 117

J. S. Dewar and M. L. Herr, Tetrahedron, 1971, 27, 2377. R. M. Hart and M. A. Whitehead, Mol. Phys., 1970, 19, 383. K. Dimroth, Colloq. Int. Cent. Nut. Rech. Sci., 1970, 139. F. Gerson, G. Plattner, and H. Bock, Helu. Chim. Acra, 1970, 53, 1629. M. H. Knoosh and R. A. Zingaro, J. Amer. Chern. Soc., 1970, 92, 4388. H. M. Buck, A. H . Huizer, S. J. Oldenburg, and P. Schipper, Rec. Trm. chirtt., 1970, 89, 1085.

270

0rganophosphor.us Chemistry

(89) was confirmed by e.s.r. studies on the solid and on a solution.l18 The spectra of phenacite 4-phosphate,llB thiophosphate,120 and vanadyl chloride-phosphine 121 radicals have also been described. Calculations on the hypothetical diradical (90) indicate that interaction with the d-orbitals on phosphorus could produce a singlet state.122

3 Vibrational Spectroscopy A. Band Assignments and Structural Elucidation.- The vibrational frequencies associated with the PF2 group 123 and PC12 group 124 in the i.r. and Raman spectra of the phenyl Pi" compounds are described and the band assignments for triphenylphosphine and its arsenic and antimony analogues are Reassignments of the deformation region for monosilylphosphines have been made.12s Depolarization data on trimethylphosphine oxide are now available and the relationship between the symmetric and asymmetric POP vibrations has been equated for diphosphates, and some halogen and metal salt derivatives.128 The polarization of a carbonyl group produced by its conjugation with an ylide causes a large decrease in V(Q. This shift to lower frequency is increased further when a double bond is interposed, lZ9 thus increasing the extent of The i.r. spectra of two crystal forms of aminomethylphosphonic acid (91) and its 15Nand 211analogues have been A Fermi resonance between Y Y ; H and vx1) vibrations and certain binary combinations can explain most of the spectra. The related aminophosphinic acid (92) and 11*

119

K. Leibler, K.Okon, and K. Checinski, J. Chirn. phys., 1970, 67, 746. M. C. R. Symons, J. Chern. Phys., 1970, 53, 857.

G. Lassmann, W. Damerau, K. Lohs, N. Klimes, and Z. Baldjeva, Z. Chem., 1970, 10, 297. lZ1 G. Henrici-Olive and S. Olive, Angew. Chetri. Internat. Edn., 1970, 9, 957. na R. Hoffmann, Accounts Chem. Res., 1971, 4, 1. l Z 3J. H. S. Green, D. J. Harrison, and H. A . Lauwers, Bull. SOC.chirn. helges, 1970, 79, 567. 1 3 p H. Schindlbauer and H. Stenzenberger, Spectrochim. Acta, 1970, 26A, 1707. l Z 6 A. H. Norbury, Spectrochitn. Acto, 1970, 26A, 1635. 126 J. E. Drake and C. Riddle, Spectroi.hirn. Acto, 1970, 26A, 1697. lZ7 J. H. S. Green and H. A. Lauwers, Bull. Soc. chint. belges, 1970, 79 571. lZ8 A. Muck and F. Petru, 2. Chenr., 1971, 11, 29. l m M. J. Berenguer, J. Castells, R. M . Galard, and M. Moreno-Manas, Tetrahedron Letters, 1971, 495. 1 3 0 C. Garrigou-Lagrange and C. Destrade, .I. Chini. phj.s., 1970, 67, 1646; C. Destradc and C. Garrigou-Lagrange, ibid., p. 2013.

27 I

PI1ysicnl Methods

its conjugate acid and base have been studied.131 The spectrum of the hydrochloride is typical of very strongly hydrogen-bonded systems, there being four very broad humps dominating the whole region from 200 to 3600 cm-l. The spectra of two amino-acids of the type (93) 132 and of some pyrimidylal kylphosphonic acids 133 are also reported.

+

I I3NCH,PO3H

Id NI PhCH,

(91)

C H-P I C3H,

0,I Ph

H + I Id3N-CMe2CH,O*PO2(93)

(92)

Metal-ligand vibrations have been identified using metal isotopes, e.g. the Ni-P stretching band which appears at 273.4 cm-1 for 68NiC1,(PEt3)2 is shifted to 267.5 cm-l for the s2Ni c0mp1ex.l~~ B. Stereochemical Aspects.-The i.r. spectrum of the bis-trifluoromethylphosphinite (94) has been determined in the gas, liquid, and solid phases.13K The doubling of the H or D bending and stretching bands is attributed to rotational isomerism, thought to arise from intramolecular hydrogenbonding and lone-pair repulsions, which gives a mixture of the conformers (94a) and (94b). 7r-Bonding in (99, and therefore the planarity of the NP3 skeleton, should be encouraged by electron-withdrawing substituents on the phosphorus atom. However, the i.r. and Raman spectra of (95) are difficult to explain convincingly on this basis and a pyramidal structure with a weak N-P bond is preferred.136 The stereochemistry of the phosphazenes (96) has been estimated from their vibrational

(95)

(94)

R. Tyka and H. Ratajczak, Bull. Acad, polon. Sci., SPr. Sci. chitn., 1971, 19, 21. J, Ferekh, A. Munoz, J. F. Brazier, and R. Wolf, Compt. rend., 272, C, 797. V. S. Reznik and Yu. S. Shvetzov, Izoest. Akad. Nnuk S.S.S.R., Ser. khim., 1970, 2254. l:le

K. Nakarnoto, Itwtritment News, 1970, 20, 1. R. C. Dobbie and B. P. Straughan, Spectrochim. Acfa, 1971, 27A, 255. P. J. Hendra, R. A. Johns, C. T. S. Miles, C. J. Vear, and A. B. Burg, Spectrachiin. Actri, 1970, 26A, 2169. D. P. Khomenko, G . ti. Dyadyusha, and E.S. Kozlov,Zhur.strukt.Khim., 1970,11,660.

272

Organophosphorus Chemistry

The configuration of dioxaphosphorinanes (97) has been estimated from ~ p - 0 An . ~ equatorial ~ ~ P=O group usually gives a band at higher frequency than an axial P=O group. Absorption bands due to POC, PO, and PMe groups appear as doublets in the spectra of neat and dilute carbon tetrachloride solutions of methyl d i m e t h y l p h ~ s p h i n a t e . ~The ~ ~ changes in intensity with solvent and temperature indicate that the doubling is due to the existence of two conformations, the more stable one having bands at 1042, 1230, and 1310cm-l and the other at 1062, 1246, and 1300cm-1. The dipole moment in carbon tetrachloride indicates that the conformers are (98a) and (98b), the former predominating. The effect of orientation on v ~ for - cyclic ~ thiophosphates has also been briefly d i s c u s ~ e d14* . ~ ~The ~ i.r. and Raman spectra of the difluoro- and chlorofluoro-compounds (99, X = CI or F) are also compatible with the presence of two discrete conformers with nearly the same energy.141 Me I

Y

?/"\..

I

I

Me

/p\

Me

(%a)

(97)

S II ,F MCOP, X (9Xb)

(99)

The vibrational spectra of the fluorophosphorane (I 00) have been analysed and assignments have been made which are consistent with a trigonal-bipyramidal structure with a radial PhS g r 0 ~ p . l The ~ ~ nonequivalence of the axial fluorine atoms in the lBFn.m.r. spectrum may be due to the phenyl ring lying over one of the axial fluorine atoms. The spectrum of PhAsCI, is also consistent with a trigonal-bipyramidal structure with a radial phenyl group.*43See also studies on the trichloromethylphosphorane (10f).144A new theoretical approach has been made, aimed ly8

lag

140 141 Ira 143

J. P. Majoral and J. Navech, Bid/. Sac. chitti. France, 1971, 1331; J. P. Majornl and J. Navech, ibid., 1971, 95; J. P. Majoral, R. Kraemer, J. Devillers, and J. Navech, ibid., 1970, 3917. 0. A. Raevskii, R. R. Shagidullin, I. D. Rorozova, L. E. Petrova, and F. G. Khalitov, Izuest. Akad. Natrk S.S.S.R., Ser. kliim., 1970, 1725. H. P. Nguyen, N. T. Thuong, and P. Chabrier, Compt. rend., 1970, 271, C , 1465. J . R. Durig and J. W. Clark, J . Chem. Phys., 1969, 50, 107. A. H. Norbury, S. C. Peake, and R . Schmutzler, Specfrachim. Acta, 1971, 27A, 151. D. M . Revitt and D. B. Sowerby, Spectrochitii. Acfn, 1970, 26A, 1581. R . R. Holmes and M . Fild, J . C/ieni. P h y s . , 1970, 53, 4161.

Physical Methods

273

at identifying the manner in which processes like pseudorotation occur (see Section 4 of this Chapter). The vc-o bands appear as doublets in the spectra of metal carbonyl phosphite complexes. The intensities of the two peaks vary with temperature and they are therefore attributed to conformational differences within the P(OR), 1igar1d.l~~ 1 .-

C . Studies of Bonding.-Force constants have been determined for a wide range of thiophosphates (102).146 The force constants are lowered for all the bonds to phosphorus when oxygen is replaced by sulphur or when chlorine is replaced by sulphur. When the methoxy-group is replaced by M ~ fp(.l ) decrease whilst fpo and fps increase. Here the chlorine, ~ I ’ o ~ and influence of the decreased electronegativity is compensated by the change from a First to a Second Period element. A set of Urey-Bradley force constants were refined from the vibrational frequencies of OPHal,, Me,PO, etc. and used to calculate the spectra of other related molecules such as OPFClBr.147 The force constants and bond orders for the oxides (103, M = N, P, or As) have been compared. The force constant and bond order for the P - 0 group were easily the largest amongst the three compounds - a result which may be rationalized in terms of d,-p, bonding.14* An extremely interesting theoretical study on d,,-p, bonding in the PO group indicates that non-bonded interactions, which act to stretch bonds, tend to increase as the .rr-bonding order decreases, i.e. n-bonding also decreases non-bonded interactions.14u This study, like several other similar studies involving d-orbitals, suggests that the most important effect of including d-orbitals in the calculation is to alter the electron distributions. (See also Section 7 of this chapter.) The total 3d population indicated by the EHMO study was entirely comparable to that obtained from the valence-bond model; however, the usage of the various d-orbitals was different. The i.r. and Raman spectra of the cyclic phosphate (104) and its SbCI, complex have been assigned and force constants and bond orders calculated.160 The high frequency of vp-0 (1308 cm-l) may be due to a strong 145

140

14’

lo8 Id@ 150

D. A. Brown, H. J. Lyons, and A. R. Manning, Inorg. Chim. Actn, 1970, 4, 428. 0. A. Wafa, A. Lentz, and J. Goubeau, Z. niiorg. Chem., 1970, 378, 273; 0. A. Wafa, A. Lentz, and J. Goubeau, ibid., 1971,380,128; V. Hornung, 0. A. WaFd, A. Lentz, and J. Goubeau, ibid., 1971, 380, 137. S. T. King and R. A . Nyquist, Specfrochitn. Actn, 1970, 26A, 1481. F. Choplin and G. Kaufmann, Spectrochitn. A c f a , 1970, 26A, 21 13. L. S. Bartell, K. S. Su, and H. Yow, Inorg. Chpiti., 1970, 9, 1903. J. Hildbrand and G. Kaufmann, Spectrochitn. Acto, 1970, 26A, 1407.

274

Orgnrrophosphor~usChemistry 0

(107)

( 104)

n-bonding contribution. A similar explanation was advanced to explain the high shielding of the phosphorus atom in the corresponding phosphite. It will be interesting to study the relationship between v p = o and 8p and to compare the results with those for the phosphites (see Table 2). In this regard, calculations based on the so-called ‘energy-rich’ pyrophosphate bonds suggested that the 3d-orbitals of phosphorus are able to contribute more to the m-bond strengths of the terminal P - 0 bonds.Is1 A correlation between vp=o and Sp would not be expected when the electronegativity of the P-substituents alters.13 Correlations are observed when the structural changes are well removed from the phosphorus atom, e.g. Sp and vPNctfor the phosphazenes (13).16 The bands at 1600 and 1490 cm- are strong and weak respectively for arylarsonium salts, with the intensities reversed for the a r ~ i n e .The ~ ~ ratio ~ for aromatic amine salts is the same as for the arsine. This could reflect the absence of conjugation in the amine salts and in the arsine but the presence of conjugation in the amine and in the arsonium salts. The possibility of both pn-p,, conjugation and d,,-p,, conjugation in phosphines with aromatic, vinylic, and other m-bonded groups has led to some interesting work aimed at differentiating the two effects. When the phosphorus substituent is a nitrile group it would be surprising if p,,-p,, conjugation did not occur. Thus the higher magnitude of f l > - ~ (and ~) lower f C - for ~ the phosphine (105) compared with the corresponding oxide and sulphide is best rationalized in this way.153 However, the similar effects observed for the triacetylenic phosphines (106) (i.e. increase in fpc and decrease in f,-cl compared with non-conjugated models) could equally be due to d,,-p,, In fact, deshielding of the acetylenic proton observed in the lH n.m.r. spectrum suggests this may be the case. However, this is countered by the crystal structure, which shows that the PCCX atoms are not linear (see Section 7). Comparison of calculated i.r. frequencies for linear and non-linear PCCX molecules with those observed was not h e 1 p f ~ l . lA ~ ~comparison of solid and solution spectra might help ascertain the relevance of the X-ray work. In the A2-phospholens, conjugation is assisted by the cyclic nature of the system and vc-c is lower than in the corresponding As-phospholens. The ’H and 31Pn.m.r. spectra supported a + A4 effect rather than a - A4 effect (d,,-p,, conj~gation).~* 31 IK9 163

IG4

D . B. Boyd, Theor. Chim. Acra, 1970, 18, 184. M. A. A. Beg and Samiuzzaman, Pakistan J . Sci. Ind. Res., 1970, 12, 330. W. Koch, €3. Blaich, and J. Goubeau, Reu. Chim tninPraIe, 1970, 7 , 1 1 13. W. M. A. Smit and G. Dijkstra, J . Mol. Structure, 1971, 7 , 223.

Physicnl M Pt hods

275

The hydrogen-bonding ability of triethylphosphine with pyrrole, [see (107)], and phenol has been studied in hexane solution by i.r. spectroscopy and compared with that of other electron Equilibrium constants were estimated from the relative intensities of free and hydrogen-bonded N H or OH. The equilibrium constants with pyrrole were 1.53 (Bu,P), 0.89 (Et,P), and 0.37 (Et,As). There was a significant decrease as the temperature was raised. The better hydrogen-bonding ability of tri butylphosphine must be due to increased inductive donation to phosphorus since it cannot be due to solvation effects in hexane solution. Although the s-character of the electron lone pair on I?'" atoms is believed to be very high, this work shows that they have sufficient p - or &orbital character to give the lone pair the directional properties required for the hydrogen bonding. A wider range of electron-pair donors was studied, with phenol as the hydrogen donor 156 [see (108)]. It was found that the decrease in absorptivity of the O H band, as the atomic weight of M increases, is at a maximum for Group V and at a minimum for Group VII elements, which parallels the change in s-character of the lone electron pair in each Group.

( 107)

(108)

The force constants of the Ni-P bond in Prrnickel carbonyl complexes increase in the order Me,P < PH, < P(OMe), < PF3.15' This order is different from that of the donor-acceptor character, as estimated from ~ ( - 0 . The lengthening of the P - 0 bond of triphenylphosphine oxide upon complexation with uranium oxide has been estimated by i.r. However, X-ray diffraction shows little difference in the P-0 bond lengths (see Section 7). Some SCF-MO calculations on the donor-acceptor properties of Me,PO and H,PO have been ~ e p 0 r t e d . l ~ ~ 4 Microwave Spectroscopy

EHMO calculations on the phosphiran (109) are relevant to microwave studies of compounds in this series.'~lo The calculations suggest that inversion involves all the atoms of the ring, including the hydrogens, and that although the 3d-orbitals of phosphorus do not participate very much IG5 loo lb7

Ion

J . Chojnowski, Bull. Acad. polon. Sci., Sdr. Sci. chim., 1970, 18, 309. J. Chojnowski, Bull. Acad. polon. Sci., SPr. Sci. chit)]., 1970, 18, 317. M. Bigorgne, A. Loutellier, and M. Pankowski, J . Organometallic Chent., 1970, 23, 201. G. Bandoli, G. Bortolozzo, D. A. Clemente, U. Croatto, and C. Panattoni, Inorg. Nuclear Cheni. Lerrers, 1971, 7 , 401. I. H.Hillier and V. R. Saunders, J . Cheni. Sou, ( A ) , 1970, 2475.

276

Organophosphorus Cheniistry

in the filled molecular orbitals, their presence does alter the charge distribufion.lso There appears to be considerably less localization of the lone electron pair on phosphorus compared to nitrogen in aziridine and nearly 90% of this is in the p z orbital. The equilibrium comformations of cyclopropylphosphine (1 10) and its deuteriated analogues have been estimated from their microwave spectra.lG1 The P-C bond length (183.4 pm) is shorter than that of dimethylphosphine ( I 84.8 pm), in accordance with the presence of conjugation between the phosphorus atom and the cyclopropyl ring. It would be interesting to establish the type of conjugation which is involved. EHMO calculations on (1 11) indicate the presence of an in-plane interaction between the Walsh orbitals of the cyclopropyl ring and the phosphorus 3d-orbitals ( 3 4 , and 3dZz).lG2 H

H H , m H P €4,

A model which takes into account the spin-rotation interaction has been found to satisfactorily explain the v21 +- 0 rotation band of PH2.1s3 The millimetre-wave spectra of HCP and DCP have been compared with those of HCN and DCN.le4 A method of estimating frequencies of bands in this region due to processes such as pseudorotation has been suggested. This new approach involves calculation of the rovi bronic energy levels from the effects of quantum-mechanical Microwave spectra obtained from PH2D and PHDz in a magnetic field of about 25 kG showed Zeeman effects, from which molecular g values were calculated.166 They were 20 times smaller than those for ammonia. The molecular quadrupole moments of phosphine and ammonia were approximately the same. Magnetic susceptibilities and molecular quadrupole moments were also compared. 5 Electronic Spectroscopy The U.V. maximum at 330nm obtained after flash photolysis of tetraphenyldiphosphine has been attributed to the Ph2P' radical.lB7 The spectrum of the benzophosphole system (65), like that of methylphosphole, resembles the spectrum of the corresponding pyrrole analogue.Q1 The H. Petersen and R. L. Brisotti, J . Amer. Chern. SOC.,1971, 93, 346. L. A. Dinsmore, C. 0. Britt, and J. E. Boggs, J . Chem. Phys., 1971, 54, 915. la2 D. B. Boyd and R. Hoffmann, J . Amer. Chem. SOC.,1971, 93, 1064. leS J. M. Berthou and B. Pascat, Compt. rend., 1970, 271, C, 799. J. W. C . Johns, J. M . R. Stone, and G. Winnewisser, J . Mol. Spectroscopy, 1971, 38, 437. 165 B. J. Dalton, J . Chem. Phys., 1971, 54, 4745. l E e S. G. Kukolich and W. H. Flygare, Chem. Phys. Letters, 1970, 7 , 43. I e 7 S. K. Wong, W. Sytnyk, and J. K. S. Wan, Cunud. J . Chem., 1971,49,994.

leD

la1

Physical Methods

277

conclusion that a phosphino-group acts as an electron donor when conjugated through a phenyl group to an acceptor group, but that it acts as an electron acceptor when opposed to a mesomerically donating group [see (1 12)] has been based on dipole, n.m.r., i.r., and U.V. spectroscopic evidence.2 Part of the latter evidence involving the optical excited state has been questioned because the opposing substituents have dominant effects on the spectra.lss When the opposing group is kept constant, e.g. Me,N, it is asserted that variation of the P-substituent does not indicate an interaction with the phosphino-group. In reply, the theoretical aspects of interpreting the spectra have been challenged,1ss in particular the assignment of bands using the one-electron-transition approach.

( 1 12)

Electronic spectroscopy, in combination with other physical evidence, has also been used to study PIv conjugation. There is agreement that the phosphorus atoms in phosphine sulphides (10) l2 and the phosphinimines (1 13) 170 act as electron acceptors. There is a corresponding enhancement of the U.V. absorption with increase in the donor properties of the opposing group Y. HMO calculations have been used to estimate the extent and type of d,,-p, conjugation inv01ved.l~~Although U.V. spectroscopy has problems of band assignment and the fact that it involves excited states, it is an attractive area of spectroscopy to which to apply MO calculations. For example, see work on (114).172 The spectra of sulphonyl phosphinimines (1 15) have also been examined.173a

Y&NX

R

R

0 1 \

P=NJJ

( 1 13)

I A r --P =N: S0,Ar

RI

(1 15) (1 14)

The spectra of stabilized methylenetriphenylphosphoranesindicate that the Ph,P= C- C= 0 and Ph3P=C- C= C- C= 0 chromophores give maxima in the regions 275-305 and 350-400 nm, respectively.s1 The G. P. Schiemenz, 7etrahedron Lefters, 1970, 4309. H. Goetz, Tetrahedron Lerrers, 1971, 1499. H. Goetz, B. Klabuhn and H. Juds, Annulen, 1970, 735, 88. H. Goetz and F. Marschner, Tetrahedron 1971, 27, 1669. H. Goetz, B. Klabuhn, and H. Juds, Annulen, 1970, 735, 88. M. I. Shevchuk, A. F. l f J a H. Goetz and J. Schmidt, Tetrahedron Letters, 1971, 2089; Tolochko, and A. V. Dombrovskii, Zhur. obshchei. Khim., 1971, 41, 540. IG9

10

278

Organophosphorirs Chemistry

effect of changing the structure of the group R in compounds of the type ( 1 16) is r e ~ 0 r t e d . l ' ~The ~ pH dependence of the spectra of phosphine~ ~ bonding quinone adducts ( 1 17) has been used to aid i n t e r ~ r e t a t i 0 n . l The of nucleotides to enzymes has also been studied using U.V.

?Ph,P=C

I

,CH2C, H,N O2 'COR

R QPR3 OH

( 1 16)

The simultaneous analysis of orthophosphate, glycerol phosphates, and inositol phosphates has been achieved by spectrophotometric analysis of the molybdovanadate complexes.17s Also, a sensitive and selective chemiluminescent molecular emission method for the estimation of phosphorus and sulphur is described,177which is based on passing solutions into a cool, reducing, nitrogen-hydrogen diffusion flame. For organic compounds it was usually necessary to prepare test solutions by an oxygen-flask combustion technique. 6 Rotation and Refraction The racemization of the phosphine (118) has been followed by optical rotation. The lack of a solvent effect indicates that there is little change in Circular dipole moment in the formation of the planar transition dichroism has been used to study the interactions of nucleotides with proteins170 and DNA with a histone.l*O Faraday effects have been reviewed.lal Refraction studies on chloro-amino-phosphines,la2fluoroand some chalcogenides lS4 are reported. PI,'

..P.

\-w Me

( 1 18) M. A. A. Beg and M. S. Siddiqui, Reu. Roumaitie Chim., 1970, 15, 1653; M. A. A. Beg and M. S. Siddiqui, Pukistan J. Sci. Ind. Res., 1970, 12, 334. 175 C. Roustan, L. A. Pradel, R. Kassub, A. Fattoum, and N. V. Thoai, Biochim. Biophys. Acta, 1970, 206, 369. 176 E. M. Bartlett and D. H. Lewis, Analyt. Biochetn., 1970, 36, 159. 17' K. M. Aldous, R. M. Dagnall, and T. S. West, Analyst, 1970, 95, 417. 178 H. D. Munro and L. Homer, Tetrahedron, 1970, 26, 4621. 1 7 @ K. Wulff, H. Wolf, and K. G. Wagner, Biochern. Biophys. Res. Cotntn., 1970, 39, 870. l a 0 T. E. Wagner, Nature, 1970, 227, 65. D. Voigt, M. C. Labarre, and J. F. Labarre, Colloq. Znt. Cent. Nar. Rech. Sci., 1970, 17(

115.

S . Senges, M. Zentil, and M. C. Labarre, Bull. Soc. chim. France, 1971, 351. M. Zentil, S. Senges, J. P. Fancher, and M. C. Labarre, Bull. Soc. chim. France, 1971, 376. lY4 V. Baliah, C. Srinivasan, and M. M. Abubucmer, Indian J. Appl. C'hern., 1970, 8, 981.

279

Physical Methods

7 Diffraction Although the aminodifluorophosphine (1 19) is planar about the nitrogen atom in the c r y ~ t a l electron ,~ diffraction shows that in the gaseous phase the molecules are slightly pyramidal, the angle between the RNR plane and the N-P bond being 32" for (1 19, R = Me), 35" for (1 19, R = H).la5 The P-N bond (168 and 166 pm long, respectively) is longer, but the P-F bond (158-9 pm) is shorter than in the crystal. Whereas these P-N compounds appear to possess a staggered conformation, electron diffraction studies on tetramethyldiphosphine indicate that it deviates by 16" [see (120)] from the staggered conformation.la6 This may be due to a shrinkage effect involving low torsional frequency oscillation about the P-P bond, which would also explain the slight non-equivalence of the methyl groups in the n.m.r. spectrum. With the interest in estimating the relative importance of pn-p,, and d,,-p,, conjugation in P'" compounds, it is of significance that the P--C=C-Y group in (106, Y = H) deviates from linearity by about 10" in the c r y ~ t a 1 . lThis ~ ~ cannot be explained by d,,-p,, conjugation and parallels a similar deviation for P(CN)3. An electron diffraction study on the monoacetylenic and mononitrile compounds should be very rewarding. 61.

Me

(120)

The crystal structures of a number of diphosphine disulphides ( 1 21) and (122) show a remarkable constancy in the bond Iengths.laa Two types of molecule are observed in the crystal of the tetramethyl compound (1 21, X = Y = Me).ls9 The crystal structure of triphenylphosphine oxide (P-C 176pm, P - 0 164pm) varies little from that observed in the uranium oxide complexes,1goand does not confirm P-0 bond lengthening in complexes, as indicated by vp-0 (see Section 3C).

(121) IR6

lg0

(1 22)

G . C. Holywell, D. W. H. Rankin, B. Beagley, and J. M. Freeman, J . Cheiti. SOC.( A ) , 1971, 785. A. McAdam, B. Beagley, and T. G . Hewitt, Trans. Faraday SOC.,1970, 66, 2732. J. Kroon, J. B. Hulscher, and A. F. Peerdeman, J . Mol. Structure, 1971, 7,217. J. D.Lee, J . Inorg. Nuclear Chem., 1970, 32, 3209. J . D.Lee and G. W. Goodacre, Acta Cryst., 1971, B27, 302. G. Bandoli, G . Bortolozzo, D. A . Clemente, U . Croatto, and C. Panattoni, J . Cheijr. SOC.( A ) , 1970, 2778.

Organophosphorus Chemistry

280

The phosphinimine (123) has a 156.7 pm P-N bond length and 124.2" PNC bond angle,lgl which indicates a large P-N double-bond character. The angle is much larger (137") in the phosphinimine (124), probably due to steric crowding. However, the P-N bond is shorter (153 pm) in (124), which may mean that the sterically induced increase in PNC angle permits additional .rr-bonding - possibly d,-p, bonding. The P-N bond is shorter still (146.9 pm) when the phosphorus atom bears a fluorine atom and the nitrogen atom bears an electron-donating methyl group,1g2as in (125); however, the PNC bond angle (1 19O) shows no evidence of widening due to d,,-pn bonding. Br

0 02yJ02 Me

Ph,P=N

(1 23)

Ph,P=N

'

Ph,FP=N

N PPh,

/

( 125)

NO2 ( 1 24)

The crystal structure of the cyclopentenylidenephosphorane ( 1 26) shows significant shortening of the bonds 'a' and 'b' and the 'b' ester group is co-planar with the central ring.lg3 This is in accordance with a strong conjugative interaction. This conformation is probably also dominant in solution (see Section 1 D). There was no evidence of shortening of the P+-0- distance by electrostatic attraction. X-Ray data on the minor isomer of the phosphetan oxide (1 27) show that it has a bent conformation, with the P-phenyl and C(3)-methyl groups as far apart as possible.194 Electron diffraction has shown a large difference in stereochemistry between A2-phospholens and A3-phospholens. The ring is planar in the A2-phospholen (128)Ig5with a CPC bond angle of ca. 94.2" whereas the As-phospholen (129)loShas an envelope shape with a CPC bond angle of ca. 98.5". A large difference in physical properties would not be surprising for they differ in stereochemistry, conjugation, and (since the CPC bond angles are different) in hybridization too. X-Ray diffraction has shown that the phosphole (130) has ring angles which are similar to those of thiophen.lo7 Evidence has been presented which shows that this molecule has aromatic character similar to that of pyrrole, yet unlike pyrrole derivatives the hetero-substituent is not in the plane of the ring. This is believed to be associated with the different barriers to inversion. lQ1 loa

lQ3 la4

Io8

lg7

M. J. E. Hewlins, J . Chem. SOC.(B), 1971, 942. G. W. Adamson and J. C. J. Bart, J . Chem. SOC.( A ) , 1970, 1452. 0. Kennard, W. D. S. Motherwell, and J. C. Coppola, J . Chem. SOC.( C ) , 1971, 2461. Mazhar-ul-Haque, J . Chem. SOC.( B ) , 1971, 117. V, A. Naumov and V. N. Semashko, Doklady Akad. Nauk S.S.S.R., 1970, 193, 348. V. A. Naumov and V. N. Semashko, J . Struct. Chem., 1970, 11,919. P. Coggon, J. F. Engel, A. T. McPhail, and L. D. Quin, J . Amer. Chem. Soc., 1970, 92, 5779.

Physical Methods

28 1

c=o

/

Me0

Me0 ( 126)

Me

Ph

Like other derivatives, the PIv phosphorin (131) has an almost planar ring in the crystal. The NPN bond angle (101.6') is larger than that of the corresponding dimethoxy-compound, probably because of spatial dernands.lB8 A very interesting comparison of the electronic structures of the PIr and PI" phosphorins and pyridine has been carried out by means of CNDO The results indicate that (a) unlike the nitrogen atom in pyridine the P" and PIv atoms donate cr charge to the ring, (6) the phosphorus atom withdraws about the same amount of 7~ charge as nitrogen but takes it from the /%carbon atoms, not the a and y atoms. The different charge distribution produced by the participation of d-orbitals has been found before, but this present example serves to show the dramatic effect that can be produced.

Yh

Ph

APh

Mc,N

lgU lpB

:p\

NMe,

U . Thewalt, C. E. Bugg, and A. Hettche, Attgew. Chem. Internat. Edn., 1970, 9, 898. H. Oehling and A. Schweig, Tetrahedron Letters, 1970, 4941.

282

Orgaiiophosphoriis Chemistry

An X-ray diffraction study on the phosphorinone (132) showed that it has a chair conformation which is slightly flattened about the phosphorus atom compared with cyclohexanone.200 Also, the P-phenyl group is tilted outwards away from an axial position. If the compound favoured a conformation with a truly axial phenyl group as shown in (133), J l > ( l f f A and J P C Hwould ~ be expected to be the same since the two protons would be equidistant from the lone electron pair on phosphorus. The observation of different constants at first suggested that the molecule preferred a conformation with an equatorial phenyl group, but it is now clear that a conformation similar to that in the crystal would also possess different coupling constants, and must now take preference as the most likely conformation in solution. The structure of dimethyl 1-hydroxycyclododecylphosphonate is also reported.201

Tn the triethylammonium salt of uridine-2’,3’-00-cyclophosphatothioate the bond lengths to the terminal oxygen and sulphur atoms of the phosphate group (PO 148 pm; PS 194.6 pm) indicate that there is no delocalization of charge on to the sulphur atom,202and the cation is situated close to the oxygen atom. Crystals of sodium cytidine-2’,3’-phosphate contain two types of molecule; one has a planar ribose ring whereas in the other molecule the ring is puckered.203 It is found that the tetra-isoamylphosphonium cation does not take a roughly spherical shape but accommodates an iodide ion 480 pm from the phosphorus atom.204 Neutron diffraction of phosphonium bromide crystals shows no evidence of h y d r o g e n - b ~ n d i n g . The ~ ~ ~ structures of bis(trimethy1phosphine)silicon tetrachloride 206 and the iridium salt (1 34)207 are also reported.

201 202

203 204

2os

207

A. T. McPhail, J. J. Breen, and L. D. Quin, J . Amer. Chem. SOC., 1971, 93, 2574. G. Samuel and R. Weiss, Tetrahedron, 1970, 26, 3951. W. Saenger and F. Eckstein, J . Amer. Chern. SOC.,1970, 92, 4712. C. L. Coulter and M. L. Greaves, Science, 1970, 169, 1097. U . P. Krasan, U. P. Egorov, and N. G. Feshchenko, J . Struct. Chem., 1970, 11, 879. L. W. Schroeder and J. J. Rush, J . Chem. Phys., 1971, 54, 1968. H. E. Blayden and M. Webster, Inorg. Nuclear Chem. Letters, 1970, 6, 703. J. M. Guss and R. Mason, Chem. Comm., 1971, 58.

283

8 DipoIe Moments, Polarography, and Other Electrical Properties The dipole moment of tributylphosphine varies from 1.49 to 2.4 D according to the solvent used.2o8 Inductive effects in phosphines have been estimated by comparing the calculated and observed dipole moments,209and the apparent dipole moment due to the lone electron pair on phosphorus has been estimated.210 A method of calculating the hybridization of the phosphorus atom in terms of bond angles is suggested which leads to a linear relationship between hybridization ratio and lone electron pair The difference between experimental and calculated dipole moments for para-substitued arylphosphines,2 phosphine sulphides,12 and phosphinimines 170 has been used to estimate mesomeric transfer of electrons to phosphorus. The Debye method of calculating dipole moments is found to be unsuitable for strongly polar substances ( p above 3-5 D depending on its molar volume). Values of k 5% accuracy are claimed by using the Onsager formula and taking atomic polarization into account.211 Thus dipole moments of long-chain phosphine chalcogenides and phosphonium salts were 1 and 10 D higher (respectively) by the second method. Dielectric constants of these compounds decreased with increased concentration, presumably due to association in antiparallel form. The bond moments, P=Ch and Pfl-, were tabulated. The presence of d,-p, bonding between vinyl groups and phosphonic ester groups was confirmed by dipole moment studies.212 The presence of a strong dipolar group (a nitrile group) in the a-position (e.g. 135) appeared to strongly influence the relative stabilities of the conformers. Dipole moments for some related chloro-compounds have also been 208

Zo9

210

211 21a

213

J. P. Fayet, M. Pradayrol, and P. Mauret, Compc. rend., 1970, 271, C, 1033. 0.A. Raerskii and F. G. Khalitov, Itvest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 2368. J. P. Fayet and P. Mauret, J . Chim. phys., 1971, 68, 156. Yu. Ya. Borovikov, E. V. Ryl'tsev, I. E. Boldeskul, N. G. Feshchenko, Yu. P. Makovetskii, and Yu P. Egorov, Zhur. obshchei Khim., 1970, 40, 1957. E. A. Ishmaeva, A. N. Vereshchagin, B. A. Bondarenko, G. E. Yastre'ova, and A. N. Pudovic, Izoest. Akad. Nauk S.S.S.R., Ser. khim., 1970, 2695. A. V. Dogadina, B. I. Ionin, K. S. Mingaleva, and A. A. Petrov, Zhur. obshchei Khim., 1970, 40, 2341.

284

Organophosphorus Chemistry 0 II ( E t 0 )%P -C =C HA r

I

CN (135)

Conformational populations of cyanomethylphosphine oxides (1 36) have been estimated from dipole moments and indicate a preference for the t r a n s - c o n f ~ r m a t i o n . The ~ ~ ~moments of the 0-,rn- and p-chloro- and tolylderivatives of triaryl phosphites (1 37, Y = :) and triaryl phosphates (1 37; Y = 0) indicate that the oxygen atom in the latter series causes the aryl rings to rotate further away from a position in which their planes all meet along the molecular symmetry axis.215 Conformational studies have also been carried out on the dioxaphosphorinanes.216 The moments of the isomeric series (138a) and (138b) were in the ranges 3 . 7 4 . 2 and 5.4-5.5 D respectively.75

Not surprisingly, the dipole moments of 1 : 1-complexes of phosphines and aluminium chloride are very large. Triethylphosphine also forms a 2 : I complex whose very low dipole moment suggests a symmetrical structure such as (1 39).36 Polarographic studies are reported on thioesters, mainly of the type (140) and (141),217 and on trichloroethylphosphonites.2** In the field of nucleotides and nucleosides it is found 219 that ATP has a very high surface activity at the mercury electrode, which is strongly dependent upon complex formation with transition metals, The polarographic behaviour of cobalt complexes with triphenylphosphine and its oxide 220 has been studied in order to estimate extraction efficiencies. Et,P I /Cl S S CI-AI II II I 'CI PEt,

(13%

( R10)2PR2

140)

(R10)?POR2

(141)

E. A. Ishmaeva, A. N. Pudovik, and A. N. Vershchagin, Izoest. Akad. Nauk S.S.S.R., Ser. khirrt., 1970, 2790. 216 C. W. N. Cumper and A. P. Thurston, J . Chem. SOC.( B ) , 1971,422. 21a B. A. Arbuzov and R. P. Arshinova, Doklndy Aknd. Nauk S.S.S.R., 1970, 195, 835. 217 G. S. Supin and V. V. Ivanchenko, Gigiena i Sanit., 1971, 36, 76. al* T. Giovanoli-Jukubczak, B. Fitak, and J. Chodkowski, Chem. analif., 1971, 16, 3 8 3 . "lo H. Sohr, K . Lohs, and G . Koenig, J . Electronnal~~t. Chem. Interfacial Electrocherii., 1970, 21, 421. l a o P. Broquet and M. Parthault, Conipf. rend., 1970, 270, C, 1798. 214

Physical Methods

285

Dielectric relaxation studies of phosphorylated polyethers from - 180" to 200 "C have been used to study their structures.221The magnitude of the dielectric constants of high-phosphonic-acid-contentpolymers is much larger than predicted, which suggests a microphase-separated structure. Conductance studies on some aryl- and alkyl-phosphonium salts showed a higher conductance for the halides than for the nitrate.222 9 Mass Spectrometry

1-Methylphosphorinone upon electron bombardment tended to undergo P-C and C-H bond cleavage rather than the C(2)-C(3) cleavage observed for the nitrogen analogue.223 A summary of the fragmentation is shown in Scheme 1. The transferance of oxygen from carbon to phos-

0

Q I

Me

+:$M -e

1

H

Mc,P -o+ Scheme 1

phorus may occur via a bridge species as shown. The ready formation of phosphinylium ion (142) and phosphonylium ion (143) (phosphacylium ions) has been observed for dialkylphosphinic This type of fragmentation is also very important for the cyclic aromatic phosphinic ester (144; R = H, Y = NH, Z = OMe) and for the oxides (144; R = H,

221

22s 224

P. J. Phillips, F. A. Emerson, and W. J. MacKnight, Macromolecules, 1970. 3, 771. A. Fidlcr and J. Vrestal, Coll. Czech. Chem. Comm., 1970, 35, 1905. L. D . Quin and T. B. Taube, J . Chem. SOC.( B ) , 1971, 832. P. Haake and P. S. Ossip, Tetrahedron, 1968, 24, 565.

286

Organophosphorus Chemistry

Y = NH, Z = H or Et) (see Scheme 2).,,, The phosphinylium ion (145) then loses PO to give a dibenzopyrrolium ion (146; R = H, Y = NH). The corresponding sulphur-bridged ester (144; R = Me, Y = S, Z = OR) has a similar fragmentation pathway.22s Since sulphur is more easily expelled than NH, the ion (147) is also observed. In the acid (144; R = Me, Y = S, Z = OH) the phosphinylium ion is by-passed and loss of P 0 2 H gives (146, Y = S) directly. The acid also has a strong tendency to

a:n

R

P

R

R

Scheme 2

lose SH, presumably after protonation of sulphur by the acidic group. I n the sulphones (144; R = Me, Y = SO2, Z = Me) there is once again a strong tendency to give the phosphinylium ion (145; R = Me, Y = SO,). The phosphine oxide (144; R = Me, Y = SO2, Z = Ph) also shows loss of PhO to give (148; R = Me) possibly via the phosphinite, and the phosphines (149) fragment with loss of ArPH.

228

R, A. Earley and M. J, Gallagher, Org. Mass Spectrometry, 1970, 3, 1287. I. Granoth, A. Kalir, Z . Pelah, and E. D. Bergmann, Org. Mass Spectrometry, 1970, 3, 1359.

Physical Methods

287

The mass spectra of some t-butylphosphinic acids, e.g. (150), are extremely The t-butyl groups fragment in two ways, either by elimination of a methyl group or by elimination of isobutylene. The latter process is only observed when a P-t-butyl group is present whereas loss of a methyl group, although relatively slow for a P-t-butyl group, is important when the t-butyl group is bound to a phenyl group. Work on stabilized alkylidenephosphoranes of the type (1 51) shows 22* that the usual cyclization across the ortho-positions of two of the P-phenyl groups to give (152) may be followed by phenyl migration and PC cleavage to give (153), a strongly stabilized carbonium ion. As steric crowding around the PPh3 moiety increases, so the intensity of the Ph3P+ion increases to bcconie the base peak at the expense of the molecular ion and M - 1 ion [Ox for (154)]. The presence of an electron-withdrawing group on the fluorene grouping has the opposite effect. The mass spectrum of N-phenyltriphenylphosphinimine (1 55) has been the main feature being the resistance of its molecular ion to fragmentation.

\

/

p/Pll

I’ll (153)

CyD (151)

( I 5’)

Most of the ions in the spectrum of isothiocyanate derivatives of cyclophosphazenes are cyclic.23o The CNS group fragments to give abundant ions M - S, M - S2,and M - CS,. A great deal of interest has been shown in the mass spectral analysis of natural products. In most cases it is desirable to develop techniques incorporating g.1.c. to enable the separation of the components obtained in extracts from natural products. The volatility required for g.1.c. is la’

la*

230

R. Brooks and C. A. Bunton, J . Org. Chem., 1970, 35, 2642. E. D. Bergmann, M. Rubinovitz, C. Lifshitz, D. Shapiro, and I. Agranat, Org. Muss Spectrometry, 1970, 4, 89. L. Tokes and S. C. K. Wong, Org. Muss Spectrometry, 1970, 4 (suppl.), 59. A. J. Wagner and T. Moeller, J. Chern. SOC.( A ) , 1971, 596.

28%

Organophosphorus Chemistry

frequently achieved by making trimethylsilyl (TMS) derivatives of the hydroxylic functions. In the phosphoryl-ethylamines and ethanolamines the POH and NH functional groups are silylated to give (156) and (157).231 0

0

II

II

( T M SO)2 P -0-C H, C H2N( T hl S )

( TMS0)2PCH,CH2N(ThIS),

( 156)

( 1 57)

OH I HOCH,.CHOH*CH,OP-Y II 0 (1 58)

The base peak is due to (M - TMS)+ and ions arising from cleavage of the CC and PC or PO bonds are also common. The glycerophospholipids tend to undergo pyrolysis on g . 1 The ~ ~spectra ~ ~ of TMS derivatives of (158, Y = OH, glycerol, ethanolamine, serine, or inositol) possess a very low abundance of molecular ions. However, peaks at (M - Me)+, (M - TMS)+, (A4- TMSOH)+, and (A4 - TMSOCH,)+ serve to identify the molecular The fragmentation of the /?-isomer of the glycerophosphate is sufficiently different from that of the a-isomer to enable their differentiation. In work towards a method of obtaining sequence information, a number of volatilizing derivatives of the furanose system have been examined, e.g. TMS, acyl, trifluoroacetyl, acetonyl, and boronyl The latter, combined with TMS derivatization, was found to be the most suitable for determining the type of base at the 3' position. The spectra of trimethylsilyl derivatives of the nucleotides RNA, DNA, AMP, etc., and derivatives deuteriated in the TMS group showed that phosphate-bound TMS groups were the most resistant to cleavage.236 Nu9eotides with a total of four TMS groups gave P(OTMS), and HOP(OTMS)s ions. Major ions consisted of the intact base plus certain portions of the sugar skeleton and of fragments derived from the phosphate ester. Atomization energies of CP, C2P, CP2, and CzPz have been determined using high-temperature Knudsen cell mass spectrometry.2S6 10 pK and Thermochemical Studies

The energies of protonation of the complete series of methyl and ethyl phosphines have been calculated.' pKa values for the hydroxyphenylK. A. Karlsson, Biochem. Biophys. Res. Comm., 1970, 39, 847. M. G. Horning, G. Casparrini, and E. C. Horning, J. Chromatog. Sci., 1969, 7 , 267. J. H. Duncan, W. J. Lennarz, and C. C. Fenselau, Biochemistry, 1971, 10, 927. 23d J. J. Dolhun and T. L. Wiebers, Org. Mass Spectrometry, 1970, 3, 669. a s s A. M. Lawson, R. N. Stillwell, M. M. Tacker, K. Tzuboyama, and J. A. McCloskey, f. Amer. G e m . Soc., 1971, 93, 1014. IY6 S. Smoes, C. E. Myers, and J. Drowart, Chem. Phys. Letters, 1971, 8, 10.

231 132

289

Physical Methods

phosphines (159; Y = :) and phosphine chalcogenides (159; Y = 0 or S ) have been used to estimate Hammett constants.237 The results show that the phosphonyl group enters into direct polar electron-acceptor conjugation.

The acid strengths of a series of phosphonic acid derivatives in a variety of solvents have also been used to estimate Hammett constants.2R8In contrast to carboxylic acids, the phosphonic acids are stronger in ketonic solvents than in hydroxylic solvents, which may be attributed to the dissociation of phosphonic acids without the necessity to disrupt the dimeric nature of the acid (see Scheme 3).

B

’I--O \ C-K 4 ‘0-ll 0

I<-c

..

0

+-

2 Sol\!.

2R-C

4 \

+

2SO~V H+ .

0-

Scheme 3

The diphosphonic acid (160) has been estimated by titration against a thorium complex.239 The complexing of this acid with calcium ions has also been studied 240 by titrimetric methods and indicates that polynuclear complexes are formed, resulting ultimately in the formation of a micelle or solid-like phase at high calcium-ion concentration. Another study came to the same conclusions using light scattering, sedimentation, electrophoretic mobility, and dialysis measurements.241 Potentiometric titration of the aminophosphonic acid (161) and its complexes with avariety of metals indicates that the complexes are more resistant to cleavage by alkali than the monophosphonic acid (162; R = Me), which confirms the importance E. N. Tsvetkov, M. M. Makhamatkhanov, D. I. Lobanov, and M. I. Kabachnik, 298

z39 240

Zhur. obshchei Khim., 1970, 40, 2387. N. R. Molchanova, V. I. Dulova, L. P. Zhuraleva, and A. T. Pavlin, Zhur. obshchei Khim., 1970, 40,263 1 . S. J. Liggett and R. A. Libby, Tuluntu, 1970, 17, 1135. R. J. Grabenstetter and W. A. Cilley, f. Phys. Chem., 1971, 75, 676. B. H. Wiers, J . Phys. Chern., 1971, 7 5 , 682.

290

Organophosphorus Chemistry

of two POSH2groups in the chelation.242Studies of the pK, of aminomethylphosphonic acid (162; R = H) and its metal complexes 243 and aminomethylphosphine oxides 244 have also been reported. The valinoniycin-based K l--selectivemembrane electrodes have been used to measure K + activity in equilibrium with ATP.245 OH I McC (PO,H,

7 )?

H2

PhC( PO,H, 1

Heats of formation of tributyl-, trihexyl-, and triphenyl-phosphine adducts with Lewis acids, such as aluminium tribromide, have been used to estimate the extent of p,-conjugation in t r i p h e n y l p h ~ s p h i n e . The ~ ~ ~ dipole moments of the adducts were fairly constant for each Lewis acid but AH was always smallest for triphenylphosphine. This is believed to be due to the interruption of p,-conjugation, the energy of which is estimated to be 1 1.7 f 2 kcal mol-l. This is substantial, but less than the figure of 14.9 for Me2NPh and evidently much smaller than that for Ph,N. The thermochemical and other physical methods of studying bonding and stereochemistry of phosphonitrilic compounds are briefly reviewed.247 The changes of heat capacity in the phase transition of Ph,MeP+(TCNQ)2have been determined.248

11 Surface Properties G.1.c. studies of tributylphosphine,208 dialkyl phosphites, and dialkyl alkylphosphonates 24g are reported. Tributyl phosphate in nitric acid can Tetraethyl pyrophosphate be estimated by g.1.c. if a glass column is ~l it has been directly determined on a nanogram scale by g . l . ~ . , ~whereas was found most convenient to first convert the tetra-aryl pyrophosphates by methanolysis to diarylmethyl phosphates.252 Phosphorochloridates were converted by t-butyl alcohol into t-butyl chloride before analysis. G.1.c. studies of pesticides have been reported 253 and the isomeric thiophosphates (138a) and (138b) have quite different retention times.75 24a

244

246 24e

249

2L1 2ba

263

N. M. Dyatlova, V. V. Medynstev, T. M. Balashova, Ya. Medvedt, and M. I. Kabachnik, Zhur. obshchei Khim., 1969, 39, 329. D. Giron, G. Duc, and G. Thomas, Compt. rend., 1971, 272, C, 1022. A. V. Nikolaev, N. S . Blishchenko, Z. N. Mironova, U. A. Dyadin, and I. I. Yakovlev, Zhur. f i z . Khim., 1970, 44, 2412. G. A. Rechnitz and M. S. Mohan, Science, 1970, 168, 1460. I. P. Romm, E. M. Sadykova, E. N. Gur'yanova, I. D. Kolli, and K. A. Kocheshkov, Doklady Akad. Nauk S.S.S. R., 1970, 195,372. R. H.Cragg, Essays in Chemistry, 1970, 1, 77. A. Kosaki, Y. Iida, M. Sorai, H. Suga, and S. Seki, Bull. Chem. SOC.Japan, 1970, 43, 2280. E. J. Quinn and D. H. Ahlstrom, Analyt. Chem., 1971, 43, 587. G. Grossi and R. Palombari, J. Znorg. Nuclear Chem., 1970, 32, 2743. J. Crossley, J. Assoc. Ofic.Analyt. Chemists, 1970, 53, 1036. J. W. Boyden and M. T. Deacon, Analyst, 1970, 95, 935. B. D. Gibenko and M. A. Klisenko, Gigiena i Sanit., 1970, 35, 77.

29 1

Physical Metiiods

The use of t.1.c. for separating organophosphorus compounds has been reviewed.254 In a study of phosphoryl compounds it was shown that Rhf values {i.e. log [( 1 - R F ) / R F ]on ) silica gel using hexane-acetone as eluant, depend upon the polarity of the P=O group.255 The migration order found was R3PO < R,(RO)PO < R(R0)ZPO < (RO),PO d (RO),HPO

The chromatographic behaviour of condensed phosphates was found to be strongly influenced by water content and pH.25s The RF of tris(dimethy1amino)phosphine chalcogenides is generally lower than those of the trialkylphosphine chalcogenides but the difference is greatest for the Prrlcompounds, and whereas the trialkylphosphines have the highest RP values in the whole series, tris(dimethy1amino)phosphine has the Paper chromatography of inositol phosphates obtained from soil extracts is described.258 Chromatography on ion-exchange resins is another way of separating very polar compounds. The polyphosphates have been separated using gradient elution,259as have aminophosphonic acids.260 The R y values of the latter, which decrease with the size of the alkyl chain, are generally higher than those of aminocarboxylic acids. The electrophoretic behaviour of the aminophosphonic acids is also described. Ion-exchange resins have also been used in the analysis of nucleotides, and 40 pmole each of CAMP, AMP, ADP, and ATP have been separated on a column of triethylaminoeth yl-Sephadex. 261 A method of separating complex mixtures of non-volatile organic compounds, similar in speed, resolution, and quantitative range to g.l.c., has been descri bed.2s2 It is described as high-pressure capillary ‘pellicular’ ion-exchange chromatography. The pellicular column packing is prepared by coating minute glass beads (dp 50pm) with ion-exchange resin or other solid phases. The coating is obtained by carrying out the polymerisation on the surface of the beads. Using this method, picomole amounts of AMP,2s3 ADP, ATP, and ppi264have been separated within 25 minutes using a linear concentration gradient. N

264

A. Lamotte, A. Francina, and C. J. Merlin, Colloq. Int. Cenf. Nut. Rech. Sci.,1970,

333. A, Lamotte and J. Auvray, J . Chromatog., 1971, 56, 264. 2116 T. Iida and T. Yamabe, J . Chromatog., 1971, 54, 413. 2b7 J. P. Meille and A. Lamotte, Compt. rend., 1971, 272, (C), 198. Bsa R. L. Halstead and G. Anderson, Canad. J . Soil Sci., 1970, 50, 111. 269 N. Matsuura, T. K. Lin, and Y. Kobayashi, Birll. Chem. SOC. Japan, 1970, 43, 2850; S. Ohashi, N. Tsuji, Y. Ueno, M. Takeshita, and M. Muto, J . Chromatog., 1970, 50, 2K6

349. 280

2e1

2es

L. Lepri, P. G. Desideri, and V. Coas, J . Chromatog., 1970, 52, 421. T. Rosett, J. G. Smith, I. Mutsuo, P. A. Bailey, D. B. Smith, and S. Surakiat, J . Chromatog., 1970, 49, 308. C. G. Horvath, B. A. Preiss, and S. R. Lipsky, Analyr. Chem., 1967, 39, 1422. G . Brooker, Analyr. Chent., 1970, 42, 1108. H. W. Shmukler, J . Chromatog. Sci., 1970, 8, 653.

Organophosphorus Chemistry

292

The effect of organophosphorus compounds on the lubricating properties of oils is of considerable interest. It has been found that esters of strong acids, e.g. phosphoric acid or nitrophenylphosphonic acid, give the best antiwear properties, reducing wear by half or more.266 It is believed that the esters degrade to acid, which then reacts with the metal surface. The free acids were insoluble in oil. However oil-soluble salts such as (163) also gave very good antiwear properties and were better in ‘initial seizure load tests’. A wide range of amine salts of dialkyl phosphites (164) has been tested and their effectiveness at different concentrations of various additives examined.2ss Tests on a variety of phosphine sulphides have also been reported.267

/*

(RO)?P ‘0-

AR,

(RO),P

A -

+

NR,

12 Radiochemical and Miscellaneous Studies Several radiochemical studies have been reported, such as the analysis of phosphorus and chlorine by fast neutron activation 288 and synthesis by radiochemical A differential vapour-pressure technique has been used to determine the molecular weights of phosphonic and phosphinic acids in 95% Cryoscopic and n.m.r. studies have been made on solutions of phosphinic acids in sulphuric acid and 0 1 e u m . ~Mass ~ ~ spectrometry has indicated the ready formation of phosphinylium ions after electron bombardment of phosphonic and phosphinic acids and their derivatives. However, the cryoscopic results in sulphuric acid indicated that reaction did not proceed beyond protonation, and the n.m.r. study on oleum solutions suggested that sulphonation occurred. ao6 206

Za7

zd8 z68

270

E. S. Forbes and H. B. Silver, J. Inst. Petroleum, 1970, 57, 90. K. Suga, S. Watanaba, A. Miyashige, and M. Moriyama, Yukugaku, 1970, 19, 910. A. F. Pavlenko, V. D. Zozula, Y. N. Ivashchenko, V. N. Chernyshev, and V. P. Akkerman, Khim. Prom., 1970, 70, 55. I. P. Lisovskii and L. A. Smakhtin, Zhur. analit. Khim., 1970, 25, 1625. H. Drawe, Radiochim. Acta, 1970, 13, 81. L. D. Freedman, G. 0. Doak, and B. R. Ezzell, Michrochem. J., 1971, 16, 311. P. Haake and P. S. Ossip, Tetrahedron Letters, 1970, 4841.

Author Index Aaron, H. S., 92, 93, 113, 115. 231 Abicht, H. P., 1, 151 Abrell, J. W., 132 Absar, I., 250 Abubucmer, M. N., 278 Abulkanov. A. G.. 107 Achiwa, K:, 170 ‘ Acloque, F., 250 Acton. M., 65 Adam, W., 242 Adamson, G. W., 280 Agarai, T., 110 Agarwal, K. L., 130 Agawa, T., 73, 163 Agranat, I., 287 Aguiar, A. M., 18, 57, 64, 181 Ahlstrom, D. H., 290 Ahmed, F. H., 227, 229 Akaboshi, M., 124 Akkerman, V. P., 292 Aksenov, U. I., 107 Aksnes, D., 74 Aksnes, G., 74 Albers-Schonberg, G., 138 Albrand, J. P., 264 Albrecht, H. P., 125 Aldous, K. M., 278 Alford, A. L., 254 Alhadeff, J. A., 138 Allcock. H. R.,. 218.. 227.. 229 Allen, C. M., jun., 102, 147

Allen, C. W., 223 Allen, D. W., 24, 250 Allen, F. H., 263 Allen, G. W., 62 Allewell, N. M., 126 Almog, J., 180 Altman, L. J., 147 Al’tmark, E. M.,182 Anderson, G., 291 Ando, H., 185 Ang, H.G., 41 Anschel, M., 7, 39, 81 Anschutz, W., 57 Anthony, R. S., 147 Antonyuk, A. S., 160 Apelbat, A.. 121 Appel, R., 10, 86, 204 Araki, Y., 142 Arbuzov, B. A,, 42, 106, 120, 284 Arcamore, F., 172 Argoudelis, A. D., 148 Arison, B. H., 138 Armolaeva, M. V., 114

Arshad, A., 108 Arshinova, R. P., 120,284 Ash, A. B., 123 Ash, D. K., 90, 238 Astell, C., 134 Auvray, J., 291 Avery, N. L., 82 Avigad, G., 149 Awerbouch, O., 5, 60 Axelrod, E. H., 153 Babab, H., 254 Babyak, A. G., 206 Baccolini, G., 119, 221 Bachmann, G., 224 Baechler, R. D., 14, 52,259 Baer, E., 137, 138, 145 Baer, H. P., 132 Bagrov, F. V., 34 Bailey, P. A., 291 Bailey, W. J., 249 Balashova, T. M., 290 Baldjeva, Z., 270 Baldwin, J. E., 77 Baliah, V., 278 Bambushek, 1. Ya., 69,249 Bandoli, G., 55, 275, 279 Banks, B. E. C., 127 Baranov, S . N., 17, 71, 110 Barker, R., 146 Barker, W. D., 158 Barket, T. P., 44, 253 Barnett, J. E. G., 144 Barrans, J., 12, 80 Barrell, B. G., 133 Barstow, L. E., 10 Bart, J. C. J., 280 Bartell, L. S., 273 Bartlett, E. M., 278 Bartlett, P. D., 243 Barton, D. H. R., 158, 238, 240 Bartsch, R. A., 105 Barvcki. J.. 71. 110. 137 . Basu, H., 145’ Batchelor, F. W., 181 Batyeva, E. S., 78, 197 Bauer. E.. 185 Bauer; J.,’ 34 Bausch, R., 15 Beagley, B., 279 Beattie, T. R., 138 Beaulieu, D. J., 102, 124 Bechara, E. J. H., 140 Becke-Goehring, M., 189, 199, 201, 214 Becker, J., 150 Beer, H., 19, 58, 108

Beg, M. A. A., 108, 274, 278 Begtrup, M., 266 Behrens. N. H.. 136 Behrman, E. J.,‘ 111 Bell, W., 178 Bi5lovsk9, O., 64, 92 Bel’skii. 1. F.. 42 Belskii,’V. E.; 115 Benda, H., 3, 52 Benezra, C., 117, 137, 232 Bengaraja, S., 120 Benkovic, S. J., 100, 102, 134 Benschop, H. P., 92, 94, 112, 121, 231 Bentrude, W. G., 88, 232, 26 I Berenguer, M. J., 18, 168, 270 Berezovskii, V. M.,135 Berger, H., 138 Bergeson, K., 119, 120 Bergl, A., 120 Bergmann, E. D., 110, 180, 268, 287 Bergmark, W. R., 80, 247 Berlin, K. D., 116, 120 Bernard, D., 32, 251 Berry, M., 265 Berthou, J. M., 276 Bertrand. R. D..I 87., 88.I 251, 261, 262 Bestmann, H. J., 152, 155, 173, 176, 178 Bhacca. N. S.. 18 Bhalerao, U. T., 176 Bhatia, S. B., 76 Biallas, M. J., 1 1 1 Bieller, U., 201, 214 Bigorgne, N., 275 Binder, H., 118, 195, 203 Birch, A. J., 157 Bird, C. W., 82 Biros, F. J., 106, 254 Bissey, J. E., 260 Blagoveshchenskii, V. S., 97 Blaich, B., 274 Blank, M. L., 146 Blaschke, H., 178 Blayden, H. E., 282 Blishchenko, N. S., 290 Bliznyuk, N. K., 46 Block, E., 243 Bloom, S. M., 14, 59 Bock, H., 234, 269 Bodkin, C. L., 69, 87, 120, 262

Boekelheide, V.. 178, 179 Boezi, J. A., 129 Bogatyrev, 1. L., 63 Boggs, J. E., 276 Boie, I., 109, 235 Bokanov, A. I . , 1 Boldeskul, 1. E., 283 Bollurn, F. J., 129 Bondarenko, N. A., 283 Bonsen, P. P. M., 144 Borisenko. A . A., 89, 91, 254 Borkent, G., 16, 264 Borodin, P. M., 255 Borovikov, Yu. Ya., 251. 283 Borowitz, 1. J., 7, 39, 55, 79, 81, 106 Bortolozzo, G., 55, 275, 279 Bostan, M., 1 Bothner-By, A. A., 120 Bottin-Strzalko, T., 156 Boulos, L. S., 13 Boulton, A. J., 244 Bourgeois, J.-M., 178 Bousquet, A., 119 Bowing, W. G., 106 Boyce, C. B. C., 45,99,232 Boyd, D. B., 166, 274, 276 Boyden, J. W., 290 Bradshaw, R. W., 173 Bradway, D., 106 Brass, H. J., 58, 11 1 Braun. P.. 218. 221 Brazier, J: F.,’35, 36, 71, 264, 271 Breen, J. J., 248, 282 Breitfeld, B., 67 Brennan. M. E.. 32. 242 Brettle, R.,234 ‘ ’ Brice, R. E., 144 Briggs, P. J., 147 Briges, W. L., 2 Brinigar, W. S., 139 Brisotti, R. L., 276 Britt, C. O., 276 Bromilow, R. H., 101 Brooker, G., 291 Brooks, R., 42, 287 Broquet, P., 284 Brown, D. A., 273 Brown, J. N., 26 Brownlee, G. G., 133 Bruno, S. A., 249 Buck, H. M., 232,269 Buckler, S. A., 14, 59 Bugerenkov, E. F., 68, 107 Bugg, C. E., 27, 281 Buist, G. J., 103 Bukovskii, M. I., 192, 193 Bullen, G. J., 226, 228 Bunton, C. A., 42, 103,287 Buono, G., 158 Burg, A. B., 271 Burgada, R., 32, 78, 84, 251, 268 Burger, K., 77 Burt, D. W., 83 Burton, D. J., 168

Buslaev, Yu. A., 219 Butzow, J. J., 131 Bykova, T. Ci., 84 Cable, J. R., 224 Cadogan, J. 1. G., 74, 112, 244, 246 Calder, I., 178 Calderon, J., 96 Callot, H., 117, 232 Camerion, B., 172 Cameron, T. S., 5 5 , 259 Campbell, B. S., 90 Campbell, I. G. M., 55, 77 Campbell, M. K., 126 Camps, F., 157 Cann, P. F., 67 Cannon, P. L., 1 1 2 Cardillo, G . , 160 Carnaham, J. C., 65 Carpenter, J. M., 122 Camarrini. G.. 288 Casper, E.‘ W.’ R., 7, 55, 79, 106 Castells, J., 18, 157, 168, 2 70 Cavell, R. G., 31, 61, 257 Centofanti, L. F., 263 Cervelli, S., 134 Cervinka, O., 64, 92 Chabrier, P., 8, 106, 272 Chahine, H., 265 Chaiet, L., 138 Chalet, J. M., 178 Chan, S. I., 126, 254 Chan, T. H., 29, 64, 264 Chang, B. C., 30, 252 Chang, L. M. S., 129 Chasle, M. F., 12 Chattha, M. S., 57, 64, 181 Chaturvedi, R. K., 103 Checinski, K., 235, 270 Chemerda, J. M., 138 Chernyshev, E. A., 68, 107 Chernyshev, V. N., 292 Chiglione, C., 96 Chippendale, K. E., 244 Chistokletov, V. N., 151 Chivers, T., 215 Chladek, S., 131 Chodkowski, J., 284 Chodroff, S., 129 Chojnowski, J., 275 Chong, K., 105 Choplin, F., 250, 273 Christau, H. J., 63 Christensen, B. G., 138 Christie, P. H., 156 Christmann, K.-F., 156 Chukhrii, F. N., 26 Chung, N. M., 98 Ciganek, E., 15, 150, 163, 197 Cilento, G., 140 Cilley, W. A., 111, 289 Ciobanu, A., 1 Clark, J. W., 272 Clark, P. E., 120 Clark, R. T., 22 Clark, V. M., 134, 141

Clarke, G. M., 65 Clarke, N., 144 Clemente, D. A., 5 5 , 275, 2 79 Clifford, K., 147 Clipsham, R., 258 Clovis, J. S., 71 Coas, V., 291 Coates, K. M., 147, 176 Coats, J. H., 148 Coggon, P., 28, 51 280 Cohn, K., 40, 46, i95 Cohn, M., 120, 134, 255 Colton, F. B., 173 Combret, G., 9 Combret, J. C., 83 Cone, J., 148 Cooke, R. D., 112 Cooper, R. D. G., 239 Cooper, T. A., 139 Coppola, J. C., 280 Corey, E. J., 167, 170, 173, I82 Corfield, J. R., 1 I , 20, 21, 23, 63, 11 3, 254 Corina, D. L., 144 Corrie, J. E. T., 157 Cosselck, J., 18 Coulter, C. L., 282 Couret, C., 8, 53 Cowley, A. H., 47, 256 Cox, R. H., 90 Cragg, R. H., 290 Cram, D. J., 115 Crarner, F., 123, 129 Cremlyn, R. J. W., 97, 98 Croatto U 55 275 279 Crofts, b. 4 i , 42,’70 Crosbie, K. D., 263 Crossley, J., 290 Crouch. R. K.. 5 5 . 79. 106 Crutchfield, M’. M., 137 Cruz, C., 96 Cuddy, B. D., 23, 151 CurnDer. C. W. N.. 284 C u r d , R., 58, 63, 242

c.,

Dagnall, R. M., 278 Dahl, A. R., 53 Dahl, L. F., 226 Dahlen, B., 55, 259 Dalton, B. J., 276 Damerau, W., 270 Damodaran, N. P., 125 Dankert, M., 136 Daves, G. D., jun., 138 Davidoff, E. F., 249 Davidson, A . J., 86 Davidson, R. S., 230 Davis, J., 263 Dawson, R. M. C., 144 Day, A. C., 173 Deacon, M. T., 290 De’ath, N. J., 20, 23, 113 D e Bruin, K. E., 21, 64, 26 1 D e Clerq, E., 132 Degani, C., 98, 123 D e Haas, G. H., 144 Demuynck, J., 54

A ut ho Y Index

295

Denney, D. B., 30, 31, 252, 257 Denney, D. Z., 30, 3 1, 252 257 Derderian, C., 212, 222 Derkach, G. I., 57, 106, 107, 119, 188, 192, 193 Derkach, N. Ya., 150 Deryabin, A. V., 225 Desai, P., 123 Desai, V. B., 217 Desideri, P. G., 291 de Silva, 0. S., 168 Destrade, C., 270 Devillers, J., 268, 272 Devlin, C. J., 10 De Vore, D. C., 224 Dewar, J. S., 46, 269 Dewhurst, B. B., 97, 98 Dickstein, J. I.. 83 Diederich; D., .147 Diehr, H. J., 49 Dierdorf, D. S., 47, 256 Dieter. 2.. 119 Dietz,’E. A., 58 Dijkstra, G., 274 Diment, J., 19, 172 Dimroth, K., 269 Dinsmore, L. A., 276 Di Prete, R. A., 58 Dirheimer, G., 128, 129 Di Sabato, G., 137 Dmitrieva, G. V., 44 Dmitrieva, N. V., 44 Dniestrowski, A., 250 Doak, G. O., 51, 257, 292. Dobbie, R. C., 271 Dogadina, A. V., 49, 109, 283 Dolhun, J. J., 288 Dombrovskii, A. V., 160, 277 Donya, A. P., 176 Dormidontova, N. P., 183 Dorn, C. R., 173 Dornauer, H., 152 Drabb, T., 99 Drake, G. L., 26 Drake, J. E., 263, 270 Drawe, H., 292 Dreeskamp, H., 256, 263 Drenth, W., 16, 264 Drowart, J., 288 Drozd. G. I.. 40, 47, 252, 121

289 Dungan; C. H:, 137 Dunikowski, L. K., 102 Dunmur, R. E., 31 Dupre, M., 162 Durig, J. R., 272 Dyadin, U., 290

Dyadyusha, G. G., 202, 203, 271 Dyatlova, N. M., 290 Earley, R. A., 286 Eastlick, D., 74, 112, 244 Ebel, J. P., 128, 129 Ebsworth, E. A. V., 15 Ecker, A., 109, 235 Eckstein, F., 132, 282 Eckstein, U., 57 Edmond, J., 147 Edmondson, R . C., 2, 60 Edwards, J. A., 182 Edwards, J. O., 58, 1 I I Eenkhoorn, J. A., 168 Efratv. A.. 5 Efremova,. M . V., 1 15 Egan, M., 14 Egger, K. W., 16 Egorov, Yu. P., 193, 282, 283 Eibl, H., 144 Eichenhofer, K. W., 86 Eicher. T.. 158 Eichhorn, ‘G. L., 13I Ejchart, A., 261 El Dik, M., 187 Eliseenkov, V. N., I15 Elix, J. A., 157, 176 El Nigurni, Y.O., 13 Emeleus, H. J., 13 Emerson, F. A., 285 Emmick, T. L., 64 Emsley, J., 210, 21 I , 254 Engel, J. F., 28, 51, 280 Engel, M. L., 128 Englert, L. F., I38 Enos, H. F., 106 Epstein, J., 112 Epstein, W. W., 147 Escudik, J., 8, 53 Evans, B. E., 181 Evtikhov, Zh. L., 68 Ezzell, B. R., 62, 292 Faerber, P., 122 Fajkos, J., 182 Fancher, J. P., 278 Farnham, W. B., 55, 64, 92, 121, 231, 261 Farrell, F. J., 147 Fattoum, A., 278 Faught, J. B., 226 Fayet, J. P., 283 Fedorova, G. K., 48, 109 Fehn, J., 77 Feistel, G., 217 Feldman, W., 124 Felicioli, R. A., 134 Felkin, H., 2 Fennesey, P., 136 Fenselau, C. C., 288 Ferekh, J., 35, 36, 264, 271 Ferris, J. P., 102, 124 Feshchenko, N. G., 47, 57, 282, 283 Fidler, A., 285 Fields, R., 260 Filatova, I. M., 224

Fild, M., 41, 46, 256, 272 Filleux-Blanchard, M. L., 265 Finamore, F. J., 128 Firestone, R. A., 73, 138 Firstenberg, S., 79 Fisher, F., 158 Fisher, J., 239 Fitak, B., 284 Fleig, H., 199 Fletcher, I. J., 244 Fluck, E., 118, 195, 203, 210 Flygare, W. H., 276 Flynn, G. L., 103 Foester, R., 46 Folli, U., 14 Foltz, E. L., 138 Fondy, T. P., 146 Font, J., 157 Fontal, B., 90 Forbes, E. S., 292 Foucaud, A,, 12 Franceschi, G., 172 Francina, A., 291 Frank, A. W., 26 Frazier, J., 129 Freedman, L. D., 249, 292 Freeman. J. M.. 279 Freinkel,’ N., 144 Fried, J. H., 182 Friedberg. I., 149 Friedemann, R.. 248 Fritsch. W.. 157 Frost, D. C:, 5 5 Fujii, A., 83 Fukin, K., 17 Fukuvama. S.. 164 Furtsch, T.’ A.; 47, 256 Gagnaire, D., 31, 251, 264 Gaidamaka, S. N., 189, 25 1 Gal, G., 86 Galard, R. M., 18, 168, 270 Gallagher, M. J., 61, 75, 81, 91, 118, 235, 286 Galle, J. E., 13, 80 Gamaleya, V. F., 187 Gareev, R. D., 117 Garratt. P. J.. 176 Garrigou-Lagrange, C., 270 Garrison, A. W., 254 Gavrilenko, 0. A., 178 Gay, D. C., 101 Gaydon, E., 79, 96 Gayoso, M., 224 Genkina, G . K., 207 Gerard. G. F.. 129 Germa,’ H., 8 4 Gerson, F., 234, 269 Gibas, J., 171 Gibenko, B. D., 290 Gick, J., 209 Gick, W., 251 Giere, H. H., 201 Gilham, P. T., 126 Gillespie, P., 39, 255

A I / t h or Index Gillett, T. A., 136 Gilman, H., 2, 60 Gilman, N. W., 182 Gilyarov, V. A., 194. 207 Giovanoli-Jukubczak, T., 284 Giron, D., 290 Giurgiu, D., 1 Ghangas, G. S., 146 Glamkowski, E. J., 86, 138 Gleason. J. G.. 238. 239 Glemser; O., 213, 215, 218 Glinski, R. P.. 123 Glonek, T., 137, 149, 255 Goddard, N., 263 Godfrey, L. E. A., 187,221 Goetz, H., 5 5 , 207, 248, 250,277 Gokel, G., 255 Goldberg, M. C., 254 Goldberg. S. 2.. 166 Goldman; D. S:, 136 Goldstein, G., 102, 124 Goldwhite, H., 90, 260 Golik. G. A.. 188. 193 Goodacre, G: W.; 279 Gosselck, J., 165 Goto, K., 59, 67, 242, 262 Gottschalk. E. M.. 129 Goubeau, J., 273, 274 Gozman, 1. P., 107 Grabenstetter, R. J., 289 Graf, G., 155 Graf, R., 178 Graham, B. W., 60 Gramze, R., 96 Granoth, I., 110, 286 Grant, D. M., 88, 261 Grassberger, M. A., 150, 250 Gray, G. R., 146 Greaves, M. L., 282 Grechkin, E. F., 48, 51, 258 Grechkin, N. P., 37 Green, J. H. S.,270 Green, M. L. H., 2 Greene, F. D., 80, 247 Greenhalgh, R., 104 Greve, W., 91, 143 Griffin, C. E.. 114 Grim, S. O., 2, 3, 249 Grimm, L. F., 199 Grinblat, M. P., 189, 212, 219 Grishina, L. N., 37 Grishina, P. N., 118 Grisolia. S.. 147 Groenweghe, L. C. D., 54 Gross, H., 68 Grosse-Bowing, W., 200, 213. 215 Grossi,G., 290 Grubber, R., 240 Gruendler, W., 248 Grunberg-Manago, M., 129 Gudkova, I. P., 143 Guillemonat, A., 79, 96, 158

Gurny, R., 178 Guroff, G., 148 Gur'yanova, E. N., 290 Gur'yanova, 1. V., 78 Guseva, F., 106 Guss, J. M., 282 Gutsch, P., 183, 204 Guyer, J. W., 84 HIaake, P., 62, 112, 113, 114, 268, 285, 292 Hladamik, H., 5 5 , 248, 250 Hlaede, W., 157 HIagele, G., 56, 119 Hlaemers, M., 87, 261 Hlaffendorn, M., 2 Hlaga, K., 133 Hlageman, E., 136 Hlaiduc, I., 187 H[all, C. D., 166 Hlall, L. D., 60, 143 Hlalmann, M., 98, 123 Hlalsall, T. G., 176 HIalstead, R. A., 291 Hlamer, N. K., 101 Hlamlet, Z., 158 Hlampl, J., 214 H'ampton, A., 122, 125 H anahan, D. J., 138 H ands, C. H. G., 2 1 1 H andy, L. B., 226 H anna, R., 141, 142 H ansen, A.-M., 158 H ansen, K. C., 18 H ansen, R. G., 136, 137 H arding, K. E., 153 H ardman, K. D., 126 H arger, M. J. P., 11, 21, 66, 119, 236, 254 H argis, J. H., 88, 261 H arker, D., 126 H arman, J. S., 40 H arnish, H., 97 H arper, P. J., 125 H arpp, D. N., 90, 238, 239 H arrington, R. C., 221 H arris, E., 129 H arris, E. E., 139 H arrison. D. J.. 270 Harrison, P. G.; 3 Harrison, W., 2 16 Hart. R. M.. 201. 269 Hartung, H.: 155 Harvey, R. A., 129 Hashimoto, H., 167 Hashimoto, M., 14,95,242 Hassner, A., 13, 80 Haszeldine. R. N.. 260 Hata, K., 19 Hata, T., 37, 96, 105, 133 Hatfield, L. D., 239 Haubold, W., 189 Hayashi, H., 142 Hays, H. R.,119 Heathcock, C. H., 158 Heckmann. G.. 210 Hedges, R.' M.; 158 Heggis, R. M.. 104 Heid, H. A., 178 Heik, P., 135

H einrikson, R. L., 145

H eiss, J., 181 H eller, C. I . , 82 H ellerman, L., 135 H ellwinkel, D., 33, 232, 252 H enderson, T. O., 137,255 H endlin, D., 138 H endra, P. J., 271 H enrici-Olive, G., 270 H enrikson, C. V., 145 H enson, M. J. C., 51 H enson, P. D., 4 H epnerova, M., 64, 92 H erbert, W., 254 H ernandez, S., 138 H err, M. L., 46, 269 H erring, F. G., 55 H errmann, E., 214 H erron, D. K., 170 H ershey, J. W. B., 128, 141 H ettche, A., 27, 281 H ettler, H., 123 H evey, R. C., 102 H ewertson, W., 4, 231 H ewitt, T. G., 279 H ewlins, M. J. E., 226, 280 H ewson, M. J. C., 252 H iatt, R., 242 H igashi, Y., 136 H iggins, R., 232 H ilbert, P., 116 H ildbrand, J., 273 H ildebrand, J. G., 137 H ildenbrdnd, K., 256 H ilderbrand, R. L., 137, 255 H illier, I. H., 40, 54, 275 €1ills, 1. R., 176 H noosh, M. H., 235 H oang Phuong Nguyen, 106

Hoffmann, C. H., 129 Hoffmann, H., 49 Hoffmann, J. M., 240 Hoffmann, P., 39 Hoffmann, R., 166, 270, 276 H offsommer, C. R., 173 H olla, C., 104 H olland, D., 178 H olmes, A. B., 176 H olmes, H. M., 132 H olmes, R. R., 46, 272 H oly, A., 122, 125, 130 H olywell, G. C., 279 H olzer, H., 145 H ong, N. D., 125 H oos, W. R., 34 H orner, L., 14, 16, 78, 278 H orning, E. C., 288 H ornlng, M. G., 288 H ornung, V., 273 H orvath, C. G., 291 H osokawa, Y., 123, 137 H otaka, T., 231 H oualla, D., 71, 253, 260 H ruby, V. J., 10 H uegele, G., 266 H uffman, J. W., 158

Author Index Hughes, A. N., 23, 66, 236 Huizer, A. H., 232, 269 Hulscher, J. B., 279 Humphrey, R. J., 268 Hunt, C. B., 9 Hutchinson, D. W., 141 Iarossi, D., 14 [chino, M., 124 Iddon, B., 244 Ignatova, N. P., 44 lida, T., 291 lida, Y., 290 lkeda K., 129 Ikehaia. M.. 128, 130, 131 Il’ina, L. K.; I Inagami, T., 126 lonin, B. I., 49, 56, 109, 120. 265. 283 Ipata,’P. L‘., 134 Ireland, R . E., 15 lrie, S., 122 Isaks, M., 111 Isbell. A. F.. 138 Ishaq; K. S . ; 146 Ishiguro, T., 141 Ishii, Y., 71, 77, 262 Ishizu, H., 100 lshmaeva, E. A., 5 5 , 283, 284 Ismailov, V. M., 50 Ismii, Y.,59 Issleib, K., 1, 2, 3, 71, 151, 153. 248 Ito, E:. 142 Ito; Y : , 231 Itoh, K., 132 Ivanchenko, V. V., 284 Ivanov. B. E.. 84, 107 Ivanova, N. L., 254 Ivashchenko, Y.N., 292 Ivin, S. Z., 47, 191, 252, 263 Iwata, K., 166 Jackson, M., 138 Jacobi, M., 221 Jacobs, M. J., 21, 261 Jakobsen. H. J., I , 263, 266 James, T. L., 16 Jamieson, J., 102 Janzen. A. F.. 82 Jardetskv. _ . 0:. . 126, 138, 2 54 Jastorff, B., 123 Jayawant, M., 183, 204 Jeanloz. R. W.. 142 Jellinek; F., 254 Jencks, W. P., 137 Jenkins, I. D., 61, 75, 81, 91, 118, 235 Jenkins, R. W., 21 I , 217 Johns, J. W. C., 276 Johns, R. A., 271 Johnson, L. N., 126 Jonas, J., 268 Jones, E. R . H., 173 Jones, G., 178 Jones, G. H., 125

297 Jones, M. E., 147 Jones, M. M., 147 JosC, F. L., 239 Juds, H., 5 5 , 248, 250, 277 Jugie, G., 254 Jungalwala, F. B., 144 Jurczak, J., 261 Kabachnik, M. I., 61, 194, 289, 290 Kadibelban, T., 30, 252 Kahan, F. M., 138 Kahn, O., 250 Kainosho, M., 133, 267 Kajiwara, M., 221, 225 Kalabina, A. V., 51 Kalamas, R. L., 123 Kaleja, R., 135 Kalir, A., 286 Kalmus, A., 181 Kalutskii, L. A., 46 Kamai, G. Kh., 44 Kamen, R . I., 128 Kammel. D., 189 Kanai, T., 124 Kanaoka, Y., 132 Kaplan, N. O., 135 Kaplansky, M., 258 Karlsson, H., 230 Karlsson, K. A., 288 Karpova, E. N., 1 Kartha, G. B., 126 Karvanov, K. V., 1 Kasheva, T. N., 193 Kashman, Y.,5 , 60 Kaska, W. C., 165 Kassub, R., 278 Kasturi, G., 104 Kato, K., 13 Katritzky, A. R.. 244 Katz, T. J., 25, 33, 65, 236, 265 Katzenellen bogen, J. A ., 182 Kaufmann, G., 250, 273 Kawabe, M., 254 Kawai, I., 123 Kawai, K., 124 Kawamoto, I., 37 Kazymov, A. V., 160 Keat, R., 42, 61 Kebabcioglu, R., 250 Keiter, R. L., 3 Keith, L. H., 254 Kennard, O., 280 Kessel, A. T., 120 Khairullin, R. S., 44 Khairullin. V. K.. 44 Khalir, A., I10 . Khalitov, F. G., 272, 283 Khan, M. S., 123 Khan. S. A.. 101 Khashtanova, V. G., 44 Khokhlov, P. S., 46 Khomenko, D. P., 202, 203, 271 Khomutova, E. D., 135 Khorana, H. G.. 123, 130 Khusanova, N. G . , 117 Khwaja, T. A., 96

KIdd, B. K., 104 Kido. F.. 157 Kiener V 210 King R. B 5 King: S. T.1’273 Kingdon, H. S., 145 Kirby, A. J., 101, 134 Kirby, G. W., 141 Kirby, K. C., 7 Kireev, V. V., 199, 200, 21 I . 225 Kirman, J., 260 Kirsanov, A. V., 47, 48, 57,61, 109, 150, 189, 191 192,205,207,251 Kishida, Y.,37 Kitson, K. M., 232 Kjellstrom, W. A., 147 Kjmen, H., 19, 172 Klabuhn. B., 277 Klebanski, A. L., 189, 212, 219 Kleiman, U. L., 265 Klein, W., 212 Kleinstuck, R., 10 Klimchuk, G. S., 223 Klimes, N., 270 Klinman, J. P., 147 Klisenko, M. A., 290 Klitgaard, N. A., 158 Kloker, W., 61 Klusacek, H., 255 Knaff. D. B., 139 Knapp, K. A., 176 Knoll, F., 10, 86 Knoosh, M. H., 269 Knop, J. K., 137 Knunyants, I. L., 114 Kobayashi, Y., 291 Koch, W., 274 Kocheshkov, K. A., 290 Kochetkov, N . K., 143 Koenig, G., 284 Koster, R., 150 Koizumi, l., 268 Koizumi, T., 112, 114 Kojima, S., 71, 77 Koketsu, J., 59, 71, 77, 262 Kolesnikov, G. S., 199, 200, 21 1, 225 Kolewa, S., 155 Kolli, I. D., 290 Kolodyazhnyi, 0. I., 106, 107, 119, 192 Konami, Y., 142 Kondo, H., 97 Kondo, N. S., 132 Kondrat’eva, R. M., 44 Konopskii, G. F., 229 Koostra, W. L., 145 Koren, N. A., 48 Kormachev, V. V., 48 Korman, E. F., 139 Kornuta, P. P., 190, 202 Korolev, B. A.. 194 Koroteev, M. P., 143 Korte, W. D., 165 Kosaki, A., 290 Kosinskaya, I. M., 190 Kosolapoff, G. M., 42

Kosova, L. M., 118 Kosovtsev, V. V., 151 Kost, D., I17 Koster, R., 250 Kotz, J. C., 268 Koval, A. A., 57, 202 Kovaler, D. G., 176 Kovalev, B. G., 182, 183 Kovaleva, T. V., 47 Kovalevskaya, T. V., 99 Kowerski, R. C., 147 Koyama, T., 148 Koziara, A., 99, 268 Kozlov, E. S., 189, 202, 203, 251, 271 Kozlov, N. S., 73 Kraemer, R., 272 Kranz, E., 155 Krasan, U. P., 282 Krdsil'nikova, E. A., 70 Kray, G. W., 112 Krisman, C. R., 136 Krivun, S. V., 17 Kroon, J., 279 Kroschwitz, H., 214 Krutzsch, H. C., 168 Kubo, T., 73, 110 Kuchen, W., 56, 119, 266 Kuchitsu, K., 55 Kudryavtseva, L. A., 84 Kueld. F. A.. iun.. 138 Kugel; R. L.; 3 18,' 229 Kuhne, H., 143 Kukhar, V. P.. 187, 188, 190, 192, 193, 198, 201, 202,207 Kukolich, S . G., 276 Kuhk, S., 246 Kulme. H.. 91 Kulumbetova, K., Zh., 61 Kumamoto, T., 164 Kunstmann, R., 173 Kuo, C. H., 173 Kuwayama, M., 141 Kuznetsov, N. T., 223 Labarre, J. F., 278 Labarre, M. C., 278 L'AbbC, G., 163 Lafaille, L., 85 Lagercrantz, C., 230 Lai, K.-H., 160 Laing, K. R., 60 Lamb, D. J., 103 Lambert, R. F., 14, 59 Lamotte, A., 85, 291 La Nauze, J. M., 138 Landau, M. A., 115, 121 Lang, C. C., 244 Lanoux, S., 211, 212, 217 Larsen, B., 147 Laskowski, M., 131 Lassmann, E., 204 Lassmann, G., 270 Latscha, H. P., 212 Lauff, J. J., 6 Laurent, J. P., 254 Laussac, J. P., 254 Lauwers, H. A., 270 Lavielle, G., 9, 83, 181

Lavrinenko, E. S., 182 Lawler, R. G., 58 Lawson, A. M., 288 Lazarus, H. M., 123 Leanza, W. J., 138 Leary, R. D., 31, 61, 257 Lednicer, D., 168 Lee, G. C. Y., 126, 254 Lee, J. D., 279 Lefbbvre, G., 180 Lehmann, H.-A., 214 Leibler, K., 235, 270 Leloir, L. F., 136 Lemmon, R. M., 123 Lennartz, W. J., 136 Lennarz, W. J., 288 Lentz, A., 273 Lenzi, M., 254 Lepri, L., 29 I Leskina, L. P.. 178 Letsinger, R. L., 64, 131 Levashov, I. N., 73 Levin, €3. V., 219 Levin. Y. A., 107 Levine, S., 136 Levy, D., 81 Lewis, D. H., 278 Lewis, R. A., 64, 92 Liaaen-Jensen, S . , 19, 172 Libby, R. A., 289 Lieb, F., 27, 236 Liedhegener, A., 57 Liess, K., 145 Lifshitz, C., 287 Liggett, S. J., 289 Lin, T. K., 291 Lindner, E., 19, 58, 108 Liorber, B. G., 69, 249 Lipatova, I. P., 118 Lipkin, D., 132 Lipsky, S. R., 291 Lischewski, M., 153 Lisovskii, I. P., 292 Litoshenko, N. A,. 188,201 Litovchenko, N. R., 190 Lloyd, D. R., 40 Lobanov, D. l . , 289 Loeber, D. E., 19, 172 Logan, T. J., 198 Lohrmann, R., 98, 124 Lohs, K., 270, 284 Loman, A. A., 181 Lopez, L., 13, 80 Lord, E., 166 Loutellier, A., 275 Luckenbach, R., 4, 64 Ludlum, D. B., 129 Lukevic, O., 1 1 I Lunde, M., 149, 255 Lutsenko, I. F., 91 Lynaugh, N., 40 Lyons, H. J., 273 McAdam, A., 279 McBlewett, F., 112 McBride, B. C., 149 McCloskey, J. A,, 288 McClure, J. D., 5 McColeman, C., 242 MacCullum, J. R., 224

McEwen, G. K., 87, 262 McEwen, W. E., 4 McFarland, C. W., 107 MacKnight, W. J., 285 McLick. J.. 139 McPhail, A. T., 28, 51, 280, 282 MacSweeney, D. F., 9, 157 Maddox, M. L., 182 MBaerlein. H.. 163 MaFkl, G.; 27; 236 Mahran, M. R., 13 Maier, L., 5 5 , 60 Maijs, L., 11 I Maillet, R., 28 Majeste, R., 26 Majoral, J. P., 120, 272 Makaiyama, T., 14 Makhamatkhanov, M. M., 289 Makinio, R., 142 Makovetskii, Yu. P., 283 Maksyumin, Y. U. K., 258 Malisch, W., 150, 153, 154, 265 Malloy, T. B., jun., 158 Malone, R., 146 Malotki, P. V., 3 Mani, N. V., 227 Mankowski-Favelier, R., 28, 264 Manning, A. R., 273 Manscher, O., 263 Manske, R., 18, 165 March, L. C., 123 Marchand, E., 12 Mardersteig, H. G., 203 Margulies, H., 99 Mark, V., 137 Markgraf. J. H., 82 Markovskii, L. N., 99 Marks, T. J., 249 Marmor, R . S., 78, 116 Marmur, L. Z., 91 Marquarding, D., 39, 255 Marriott, J. C., 40 Marschner, F., 277 Marsh, W. C., 227, 228 Marshall, J. A., 173 Marshall, R., 244 Marsheck, W. J., 173 Marsi, K. L., 22 Marsmann, H., 54 Martin. C.. 27. 236 M artin; M:, 57 M;arty, R., 253. 260 Mrashlyakovskii, L. N., 56 Mlason. R.. 282 Mlastalerz,'P., 71, 110, 137 Mlata, J. M., 138 Mlathey, F., 28, 264 Mlathieu. R.. 254 M lathis, F., 85 M latrosov, E. I., 89, 207 MIatsueda, R., 67, 242 Mlatsuura. N.. 291 Mlatzura. 'H.. '129 Mlaund, J. K.. 21 1 Mlauret, P., 283 Mlazhar-ul-Haque, 5 5 , 280

Airttior Index Meadows, D. H., 126, 254 Mebazaa, M. H., 265 Mecke, D., 145 Medved, T. Ya., 61, 290 Medynster, V. V., 290 Meille, J. P., 85, 291 Meinwald, J., 160, 181 Mellows, G., 158 Mel’nikov, N. N., 44, 63 Mel’nikova, L. M., 135 Mendicino, J., 141, 142 Merigan, T. C., 132 Merlin, C. J., 291 Merlini, L., 160 Merry, E. V., 14, 59 Merz, A., 27, 236 Meyer, G., 163 Mhala, M. M., 104 Michalski, J.,~.14, 59. 89, 107, 115 Michelson, S., 129 Mikmnevich, V. V., 48 Mikolaiczvk. M.. 261 Mildvan, k.’S.,135 Miles, C. T. S., 271 Miles, H. T., 129 Miller, A. K., 138 Miller. B.. 99. 160 Miller; J. A., ’61, 75 Miller, S. I., 83 Miller, T. W., 138 Minami. T.. 163 Mingaleva, ’K. S., 49, 283 Mironova, V. V., 219 Mironova, Z. N., 290 Mislow, K., 4, 14, 52, 55, 64,92, 121,231,259,261 Mitchell, D. K., 165 Mitchell, K. A. R., 5 5 Mitchell, R. H., 176 Mitchenko, U. I., 255 Mitsch, C. C., 249 Mitsunobu, O., 13 Miyaki, M., 124 Miyano, M., 173 Miyashige, A., 292 Mizuno, Y., 132 Mochales, S., 138 Mochalkin, A. I., 46 Modena, G., 58, 63, 242 Modro, T. A., 19 Moeller, T., 223, 224, 226, 287 Moffatt, J. G., 123, 125 Mohan, M. S., 290 Molchanova, N. R., 120, 289 Mole, M. L., 158 Molends, R. P., 3 Moll, E., 77 Molne, G. M., 153 Molyarko, L. I., 192 Moner, M., 91, 142 Monro, R. E., 128 Moore, J. W., 145 Moreland. C. G.. 249 Moreno-Mafias, . M., 18, 168, 172 Mori, Y., 163 Morimoto, S., 141

299 Morino, Y., 55 Moritani, T., 55 Moriyama, M., 292 Morrow, C. J., 18, 57, 64, 181. Mosiichuk, A. I., 192 Moskalevskaya, L. S., 48, 109 Moskva, V. V., 50 Motherwell, W. D. S., 280 Motoyama, I., 19 Muck, A., 270 Mudgett, M., 149, 255 Muelder, W. N., 120 Mueller, A., 250 Mukai, T., 247 Mukaiyama, T., 67, 95, 96, 164, 242 Mukhametov, F. S., I19 Muller, E., 181 Mundry, K. W., 134 Mungall, W. S., 131 MuHoz, A., 35, 36, 264, 27 1 Munro, H. D., 14, 278 Murakami, Y., 97, 100 Murao, K., 130 Murata, Y., 167 Murayama, A., 123 Murch, R. M., 224 Murray, J. C. F., 23, 151 Murray, K., 133 Murray, M., 31 Murray, R. K., 5 5 , 64, 92, 121, 231, 261 Murray, R. W., 243 Mushika, Y., 96 Muto, M., 291 Mutsuo, I., 291 Myers, C. E., 288 Myers, D. K.. 41, 248, 253 Myers, T. C., 137, 149, 255 Naan, M. P., 166 Nagao, Y.,236 Nagase, O., 123, 137 Nagyvary, J., 124 Nakagawa, l., 96, 133 Nakamoto, K., 271 Nakatani, T., 142 Nasonovski, I. S., 89 Naumann, K.. 4, 64 Naumov, V. A., 280 Navech, J., 119, 120, 268, 272 Nazarov, T. A., 46 Neeff, W.-R., 2 Neims, A. H., 135 Neimysheva, A. A., I14 Nesterenko, V. D., 78, 197 Newton, M. G., 90 Nauven. H. P.. 272 Nguyen’ Thnnh Thuong, 105, 106 Nicholson, D. A., I 1 I Niecke. E.. 213. 215. 218. 250 Niedballa, U., 129 Nifant’ev, E. E., 89, 143, 254 ,

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I

I

Nikolaev, A. V., 290 Nikolaev, G. A., 219 Nikolotova, Z. I., 255 Nikonova, L. Z 42 Nishino, T., 148’ Nitta, M., 247 Nixon, J. F., 262, 263 Noth, H., 203 Nomura, H., 132 141 Norbury, A. H., 370 272 Norman, A. D., 3, 5 3 , 263 Nowak, T., 135 Nudelrnan, A., 115 Nuretdinova, 0. N., 42, 106 Nurtdinov, S. Kh., 44 Nyquist, R. A., 120, 273 Oakenfull, D. G., loo Oakley, R. T., 215, 216 O’Brien, S. J 218 Obruszek, A:,’ 89 Ochoa, S., 128 O’Connell, E. L., 120, 134, 255 O’Connor C. J. 60 Odlyzko, M ’ 131 Oehling, H., 27; 281 Oehlschlager, A. C., 50 Ogata, Y., 34, 76 Ogawa, H., 169 Ogura, K., 148 Ohashi, O., 254 Ohashi, S., 291 Ohshiro, Y., 73, 163 Ohtsuka, E., 128 130 Okamoto, Y., 49: 91 108 Okamura, M., 59, 26‘2 Okhrimenko, I. S., 56 Okon, K., 235, 270 Okruszek, A., 14, 59, 115 Okuhashi, T., 225 Olah, G. A., 107 Oldenburg, S. J., 232, 269 Olive, S., 270 Olson, T., 121 Olsson, N. A., 97 Ondracek, L., 214 Oram, R. K., 1 I , 254 Orgel, L. E., 98, 123, 124 Orlov, N. F . , 90 Ormond, R . E., I38 Orwig, B. A., 338 Osawa, T., 142 Oshiro, Y., 110 Ossip, P. S., 112, 113, 285, 292Ostreich, C. H., 147 Ottinger, R., 87, 261 Oyabu, S., 128

k.

Paddock, N. L., 215, 216, 222, 228 Padwa, A., 240 Paetkau, V. H., 30 Page. C. B.. I73 Page; G., 238 Pak, V. D., 73 Paleichuk, V. S. , 193

300 Palombari, R., 290 Panattoni,.C., 55, 275, 279 Pankowski. M., 275 Para, M., 261 Parker, D. M., 41, 42, 70 Parker, K. A., 153 Parnes. H.. 79 Parodi; A.’J., 136 Parr R. W., 58, 263 Partkwlt, M., 284 Pascat, B., 276 Patchett, A. A., 138 Pattenden, G., 176 Patzmann; H . , 214 Paul I. C., 226 Paulken, H., 91, 142, 143 Pavanaram, S. K., 137,138 Pavlenko, A . F., 292 Pavlin, A. T., 289 Payne, D. S., 42 Pazos, J. F., 80, 247 Pe,a,k,e, S. C., 51, 252, 257, L I L

Pearson, J. E., 120, 134, 255 Peerdeman, A. F., 279 Peiffer, G., 79, 96, 158 Pelah, Z . , 110, 286 Penco, S., 172 Pepperdine, W., 179 Perini, F., 122 Peters, V. M., 83 Petersen, H., 276 Peterson, E., 129 Petrachenko, A. A., 193, 207 Petrosyants, S. P., 219 Petrov, A. A., 49, 56, 68, 151, 283 Petrova, L. E., 272 Petru. F.. 270 Petukhova, A. S., 68 Pfohl, S., 39 Pfuller, H., 176 PhilliDs. B. E.. 132 Phillips; P. J.,’285 Phuong, N. H., 8 Piantadosi, C.. 146 Picard, M., 264 Pickel, H. H., 184, 208 Picken, J. M., 141 Pidcock, A., 263 Piekos, A., 19 Pilling, G. W., I51 Pinchuk, A. M., 99, 187, 190 Pinder, A. R., 176 Pisanenko, N . P., 202 Pischel, H., 122 Piskala, A., 156, 168 Platenburg, D. H. J. M., 94, 231 Plattner, G., 234, 269 Plattner, J. J., 176 Pletcher, T. C., 103 Ploder, W. H . , 162 Ploger, W., 42, 71 Pogson, C. l., 146 Pohlemann, H., 218, 221 Poilblanc, R., 254

Author Index Polikarpov, Yu. M., 61 Pollak, P. I., 138 Pollard, D. R., 229 Pollitt, R., 82 Pomazanov, V. V., 42 Pong, S., 105 Poonian, M. S., 134 Pope, P., 50 Popescu, I., 1 Popilin, V. P., 21 1 Popjak, G., 147 Portnoy, N. A., 57, 64, 181 Poulter, C. D., 147 Pradayrol, M., 283 Pradel, L. A., 278 Preiss, P. A., 291 Price, S. J., 176 Priestley, H. M., 22 Promanenkov, V. K., 191 Prons, V. N., 189, 212, 219 Proskurnina, M. V., 91 Pudovik, A. N., 44,55, 78, 117, 197, 283, 284 Purick, R., 86 Quimby, 0. T., 1 1 1 Quin, L. D., 28, 41, 44, 51, 137, 248, 253, 280, 282, 285 Quinn, E. J., 290 Rabinowitz, J., 98 Radschett, K., 157 Raerskii, 0. A., 283 Raevskaya, 0. E., 117 Raevskaya, T. A., 194 Raevskii, 0. A., 272 Raigorodskii, 1. M., 225 Rakhmatullina, L. Kh., 78 Ramage, R., 9, 157 Ramey, C. E., 178 Ramirez, F., 15, 34, 39,43, 76, 255 Ramponi, G., 147 Randall, D. E., 139 Ranganthan, T. N., 222 Range, P., 173 Rangoonwala, R., 173 Rankin, D., 150, 265 Rankin, D. W. H., 15, 40, 195, 279 Rapko, J. N., 217 Rapoport, H., 176 Ratajczak, H., 271 Ratcliffe, R., 158 Rathke, J., 84 Rauchle, F., 224 Rave,T. W., 198 Raza, S. M., 5 5 , 77 Razumov, A. I., 50, 249 Razumova. N. A.. 34. 68, 69, 70 Readio, P. D., 7, 39, 81 Rechnitz. G. A.. 790 Reddy, 6. S., 257 Redmore, D., 109 Reese, C. B., 96 Regitz, M., 57

Reiff, L. P., 92, 93, 231 Reimann, E., I78 Reinhard, W., 123 Reisdorf, D., 181 Reisse, J., 87, 261 Reist, E. J., IS6 Remmers, G., 196 Remy, P., 128, 129 Rengaraja, S., 116 Reuter, W., 129 Revel, M., 119, 128 Revitt, D. N., 272 Reynard, K. A., 224 Reynolds, S. J., 146 Reza. M. J.. 146 Reznik, V. S., 271 Rice, R. G., 224 Richards, E. M., 6, 25, 32, 57 Richards, F. M., 126 Richardson, D. I., jun., 100, 132 Riddle, C., 270 Rieff, L. P., 113, I IS, 231 Riesel, L.,214 Riess, J., 260 Rilling, H. C., 147 Rittner, S., 123, Rizpolochenskii, N. I., 119 Robbins, P. W., 136 Robert, J. B., 251, 264 Roberts, G. C. K., 126,254 Robinson, L., 103 Robinson, W. H., 147, 176 Roder, H., 78 Roesky, H. W., 61, 106, 187, 188, 196, 199, 200, 201, 213, 215, 263 Rohlik, K., 5 Rois, A., 242 Roman, L., 1 Roman, S. A., 182 Komm, 1. P., 290 Roper, W. R., 60 Rorozova, I. D., 272 Rose, I. A., 120, 134, 255 Rose, S. H., 224 Rosenberg, H., 138 Rosenthal, A., 178 Rosett, T., 291 Rosini, G., 119, 221 Ross, R. T., 254 Rossi, C. A., 134 Rossnecht, H., 194, 208, 25 1 Rostock, K., 152 Roszinski, H., 97 Roth, A., 1 Rothrock, J. W., 129 Rottman, F., 129 Roundhill, D. M., 13 Roussel, J., 78. 268 Roustan, C., 278 Rowsell, D. G., 260 Rozen, A. M., 255 Rozinov, V. G., 48, 258 Rubinovitz. M., 287 Ruch. E., 155 Rudavskii, V. P., 188, 201 Ruden, R. A., 173

Author Index Rudolph, K. P., 8 Rudolph, R. W., 52, 262 Ruff. J. K.. 226 Rum antseva Z. G., 219 Rusciig, H., i57 Rusek, P. E., 7 Rush. J. J.. 282 Russell, S.’W., 19, 172 Ryl’tsev, E. V., 283 Sadamori, H., 97 Sadykova, E. N., 290 Saegusa, T., 231 Saenger, W., 282 Safe, S., 239 Saffhill, R., 124 Sahuri, S., 222 Saikachi, H., 169 Saito, A., 124 Saito, H., 221, 225 Sakurai._ H.. . 49, _91. . 108,236 Salisbury, L., 169 Samarai, L. I., 106, 107, 119. 192 Samitov, Yu. Yu., 119, 120 Samiuzzaman, 274 Samoilenko, G. V., 71, 1 10 Samuel, D., 147 Samuel, G., 282 Sanchez, M., 264 Sanchez, R. A., 123, 124 Sanger, F., 133 Sargent, M. V., 176 Sarma, R. H., 135 Satchell, D. P. N., 147 SatgC, J., 8, 53 Sato, E., 132 Sato, M., 19 Sauerbier, M., 181 Saunders, V. R., 40, 54, 275 Saxena, S. B., 104 Schaad, L. J., 54 Schaaf, T. K., 173 Schaap, A. P., 243 Schappel, J. W., 187 Scheit, K. H., 122, 129 Scher, M., 136 Scherer, 0. J., 209, 251 Schiederrnaier, R., 210 Schiernenz. G. P., 5 , 150, 259, 277 Schindlbauer, H., 270 Schindler, N., 42, 71, 220 Schip er P., 232, 269 Schlapaih, A. J., 134 Schlessinger, R. H., 240 Schlief, R. F., 128 Schlosser, M., 30, 156, 168, 252. Schmidbaur, H., 150, 153, 154, 184, 208, 265 Schmidpeter, A., 194, 196, 206, 207, 208, 220, 248, 25 1 Schmidt, J., 207, 277 Schmidt, M., 2 Schmidt, P. G., 268

30 1 Schmidt, U., 109, 235 Schmir, G. L., 103 Sctryulbach, C. D., 212, LLL

Schmutzler, R., 31, 41, 51, 250, 252, 256, 257, 263, 272 Scholz, H., 155 Schray, K. J., 100, 134 Schroeder, J. P., 83 Schroeder, L. W., 282 Schroter, D., 214 Schultz, C. W., 52, 262 Schumann, C., 263 Schumann, H., 1, 3, 52 Schumann, K., 207, 208, 25 1 Schwartz, M. A., 147 Schwartz, W., 112 Schwarz, V., 182 Schweig, A., 27, 281 Schweizer, E. E., 16, 50 Schwieter, U., 171 Sears, D. J., 74 Seddon, D., 234 Seeley, D. A., 160 Seibt, H.,68 Seitz, G., 173 Seki, S., 290 Semakov, B. V., 120, 265 Semashko, V. N., 280 Semenii, V. Ya., 202 Semenov, N. S., 17 Semin, G. K., 258 Senges, S., 278 Sen Gupta, K. K., 92 Sepulveda, L., 103 Servi, S., 160 Seto, S., 148 Setondji, J., 129 Seyden-Penne, J., 156, 180 Seyferth, D., 78, 116 Seymour, S. J., 268 Sgaramella, V., 130 Shafik, M. A., 106 Shagidullin, R. R., 118, 272 Shahak, I., 180 Shainkin, R., 145 Shamshurin, A. A., 176 Shapiro, B. M., 145 Shapiro, D., 287 Shapiro. T. A., 135 Sharp, D. W. A., 40 Shaturskii, Ya. P., 48, 109 Shaw, D. C., 138 Shaw, G., 122 Shaw. M. A.. 6. 258 Shaw; N., 145 Shaw, R. A., 5 5 , 217, 259 Sheinkman, A. K., 71, 110 Sheka. Z. A.. 204 Shelakova, N. D., 191 Sheldon, R., 230 Sheldrick, G. M., 263 Sheluchenko, V. V. S., 115 Shen, T. Y.,122 Shestakov, E. F., 90 Shevchenko, V. I., 187, 190,202 ’

Shevchuk M. I., 160, 277 Shima, KI, 236 Shimizu, B., 124 Shimizu, M., 123, 137 Shimizu, S., 59, 262 Shirnoyo N 169 Shin, C.,’18< Shirahama, H., 173 Shizuyoshi, S., 77 Shmukler, H. W 291 Shokol, V. A., ‘i87, 188, 192, 193 Shtepanek, A. S., 192, 205 Shuikin, N. I., 42 Shulman, J. I., 167 Shutt. J. R.. 21 Shvetsova-Shilovskaya, K. O., 63 Shvetsov-Shilovskii, N. I., 44 Shvetzov, Yu. S., 271 Siddiqui, M. S., 108 278 Sidky, M. M., 13, j7, 77, 81 Silhan, W., 17, 184, 204, 255 Sillero, A., 128 Silver, H. B., 292 Sim, W., 42 Simalty, M., 162, 265 Simid, D.. 150. 250 Simpson,’ P., ’69, 83, 87, 120, 262 Sinitsyna, N. I., 70 Sinyavskaya, E. I., 204 Slates, H. L.. 173 Sletzinger, M.,86 Smakhtin, L. A., 292 Smetana, R. D., 243 Smets, G., 163 Srnit, W. M. A,, 274 Smith, B. C., 217 Smith, C. P., 76 Smith, D. B., 291 Smith, D. J. H., 1 1 , 254 Smith, D. M., 74, 244 Smith, E. H., 240 Smith, J., 129 Smith, J. E., 40, 195 Smith, J. G., 291 Smith, J. R. L., 232 Smith, M., 134 Smith, M. J., 2 Smith, P. F., 144, 145 Smith, R. H., 244 Smoes, S., 288 Smrt, J., 129 Snider, T. E., 116 Snieckus, V., 168 Snowdon, L. R., 181 Snyder, E. I., 9 Snyder, F., 146 Snyder, J. P., 22, 239, 258 Sobell, M 128 Soborovskli, L. Z., 45 Soerensen, A. K., 158 Sohr, H., 284 Sokal’skii, M. A., 47, 252, 263

302 Solodushenkov. S. N., 192, 193, 207 Soma, N., 37 Somieski. R.. 214 Sommer,’K.,’ 3, 4, 43 Sondheimer, F., 151, 176 Sorai, M., 290 Soroka, M., 71, 110, 137 Sorokin, M. S., 90 Sowa, J. R., 112 Sowerby, D. B., 272 Spector, L. €3.. 137, 147 Spiridonova, J . G., 45 Spiro, T. ti., 147 Sporn, M. B., 123 Sprecher, M., 81, I17 Sprinzl, M., 178 Srinivasan, C., 278 Srivanavit, C., 23, h6, 236 Stabrovskaya, L. A . , 117 Stache, U., 157 Stadtman, E. R., 145 Stam, M., 103 Stanko, J. A., 227 Stapley, E. O., 138 Starks, C. M., 26 Starnes, W. H., 6 Start, G. R., 268 Stec, W., 14, 59, 89, 107 Steen. R.. 40 Steger, E.’, 224 Stein, G., 259 Stein, M. T., 227 Steiner, P. R., 60, 143 Steinhoff. G., 30, 252 Steinshneider, A:, 126 Stelzer, O., I Stempel, L. M., 132 Stenhouse, I. A., 55 Stenzenberger, H., 270 Stepanov, B. I., I , 221 Sternbach, H., 129, I32 Stevens, C. L., 123 Stewart, A. P., 38. 70, 257 Stewart, C. J., 228 Stewart, J. C. M., 96 Stillwell, R. N., 288 Stockigt, J.. 150 Stoll, K., 206 Stone, J. M. R., 276 Straughan, B. P., 271 Strehlke, P., 129 Streichfuss, D., 18 1 Stroh, E. G., 229 Stroh, J., 17, 184, 185, 204, 255 Strorninger, J. L., 136 St$$IyV, 0. G., 47, 121, LJL

Strzelecka, H., 162 Su, K. S., 273 Subba Rao, G . S. R., 157 Sudakova. T. M., 78 Sudo, R., 17 Suga, H., 290 Suga, K., 292 Sugimura, Y., 37 Sulkowski, E., 131 Sullivan, C. E., 4 Sullivan, F. R., 71

Author Index Surnskaya, E. B., 160 Sunamoto, J., 100 Sundberg, R. J., 244 Supin, G. S., 284 Surakiat, S., 291 Surmatis, J . D., 171 Suschitzky, H., 244 Suzuki, M., 242 Svergun, V. I., 258 Swain, J. R., 263 Swallow, J. C., 77 Sweeley, C. C., 136 Swierczewski, Ci., 2 Swoboda, J., 218. 221 Sykes, B. D., 268 Symons, M. C. R., 270 Sytnyk, W., 230, 276 Szafraniec, L. J., 93, 1 13, 115 Szelke, M., 145 Tacker, M. M.. 288 Taddei, F., 266 Tagaki, M., 97 Tagawa, H., 137 Taguchi, T., 164 Takayama, K., 136 Takeshita, K., 291 Taksidi, V. K., 221 Taniura, C., 37 Tapiero, C. M., 124 Tarien, E., I31 Tars, P., 110 Taub, D., 173 Taube, T. P., 285 Tavares, D. F., 162 Tavs, P., 90, 266 Tazawa. I.. 132 Tazawa; S.; 132 Taylor, A., 239 Taylor, E. C., 181 Taylor, 1. C., 4, 231 Tchoubar. €3.. 156 Tebby, J. ‘C.,’6,24, 25, 32, 57, 250, 258 Telefus, C. D., 34 Terashima. S.. 173 Tew, L. B.; 83 Tidd, B. K., 148 Thach, R. E., 128 Thakore, A. N., 50 Thaller, V., 173 Thamm, El., 213, 215, 218 Thang, M. N., 129 Thewalt, U., 27, 281 Thiem, J., 91, 142 Thoai, N. V., 278 Thomas, G., 290 Thomas, R., 181 Thommen, R., 171 Thornson, C., 246 Thuong, N. T., 8, 272 Thurston, A. P., 284 Timofeeva, T . N., 120, 265 Timokhini, R . V., 51 Timokhin, V. G., 258 Titov, S. S.,199, 200, 225 Tkachenko, E. N., 192,205 Todd, A. R., 141 Todd, J. M., 222

Todd, M. J., 244, 246 Tokes, L., 287 Tolrnachev, A. J., 26 Tolochko, A. F., 277 Tomaschewski, G., 67, I19 Toube, T. P., 19, 172 Towns, R. L. R., 26 Trantwein, W. P., 120 Travale, S. S., 128 Travers, A. A., 128 Trefonas, L. M., 26 Trippett, S., 4, 1 I, 20, 21, 23, 38, 63, 70, 113, 230, 254, 257 Tronchet, J., 178, 21 6, 227, 228 Tronchet, J. M. J., 178 Trutneva, E. K., 107 Tsivunin, V. S., 44, 48 Ts’o, P. 0. P., 126, 132 Tsolis, E. A., 15, 39, 43 TSOU,K. C., 123 Tsuji, N., 291 Tsvetkov, E. N., 289 Ts;3y,b~, V. T., 188, 193, LJ 1

Tu, S. I., 140 Tucker, P. A., 228 Tukhar’, A. A., 191, 205, 207 Turkel, R. M., 18 Turnblom, E. W., 25, 33, 236, 265 Tyka, R., 271 Tyssee, D. A., I 1 2 Tzuboyama, K., 288 Ubasawa, M., 130, 131 Uda, H., 157 Udy, P. B., 210, 211, 254 Ueda, T., 123 Ueki, M., 242 Ueno, Y., 291 Ugi, I., 39, 155, 255 Ulrich, S. E., 3 Uno, H., 128 Usher, D. A., 100, 132 Uzlova, L. A., 143, 178 Valentine, R., 129 Van Deenen, L. L. M., 144 Van den Berg, G. R., 92, 94, 112, 121, 231 van d e Sande, J. H., 130 v. Angerer, E., 158 van Tamelen, E. E., 147, 153 Van Wazer, J. R., 54, 137, 250

Vear, C. J., 271 Veillard. A.. 54 Veki, M’., 67 Vela, F., 157 Venkatcswarlu, A., 173 Vere Hodge, R . A., 173 Vereshchagin. A. N., 55. 283, 284Verheij, H. M., 144 Verkade, J . G., 84, 87, 251, 262, 267 ’

Author Index

303

Vernon, C. A., 127 Verrier, J., 251 Villieras, J., 9, 83 Vilsmaier, E., 155 Vinogradov, L. I., 120 Vishnevskii. 0. V.. 119. 192 Vivarelli, P., 266 Vlasova, S. N., 97 Voiculescu, N., 1 Voint. D.. 278 Volrhardt; K. P. C., 176 Volodin, A. A., 200 von Philipsborn, W., 17, 184, 204, 255 Vorbruggen, H., 129 Vornberaer. W.. 154 Voronk&, M . G., 91 Vrestal, J., 285 Vriezen, W. H. N., 254 I

,

Wafa, 0. A., 273 Wagner, A. J., 223, 224, 226, 287 Wagner, K. G., 278 Wagner, T. E., 278 Waite, N. E., 6, 258 Wakeford, D. H., 97, 98 Waki, A., 124 Walker, B. J., 10, 23, 74, 75, 151 Wallick, H., 138 Wallis, D. G., 105 Walser, A., 171 Walsh, C. T., jun., 137 Walsh. E. J.. 218 Walther, B.,'71 Walz, F. G., jun., 126 Wan, J. K. S., 230, 276 Wanek, W., 214 Wann. J. H.. 139. 140 W a d , ' R. S.; 6, 258 Ware, M. J., 40 Warner, A. H., 128 Warren, S., 114 Warren, S. G., 67 Wass, M. N., 120 Watanaba, S., 292 Watanabe, Y., 225 Waterhouse, C. R., 263 Watts, P., 112 Wayne, R., 99 Webb, S. B., 45, 99, 232 Webster, M., 282 Weedon, B. C. L., 19, 172 Wehman, A. T., 16, 50 Weinberg, K. G., 26, 60 Weinberg, M. A., 104 Weiss, R., 282 Weiss, R. G., 9 Weiss, W., 196

Weissbach, A., 134 Weitkamp, H., 110, 266 Welch, S. C . . 15 Wendler, N. I-.. 138, I73 Wenschuh. E., 8 Wernick, A. K. S., 224 West, T. S., 278 WestDhal. 0.. 144 Whipple, 'E. B., 26 White, D. W., 31, 87, 251, 257, 262, 267 White. G. F.. 147 Whitehead. 'M. A.. 201. 258, 269. Widdowson, D. A., 158, 238 Wiiber, M., 34 Wiebers, T. L., 288 Wiers, B. H., 289 Wilfinger, H.-J., 33, 232, 252 Wilkins, B., 262 Wilkinson, G., 13 Williams, D. H., 6, 258 Williams, J. C . , jun., 57, 64,181 Williams, M. R., 114 Williams. V.. 147 Willis, B: J.,'240 Willson, M., 84 Winkler, T., 17, 184, 204, 255 Winnewisser, G., 276 Winter, M., 123 Winter, W., 181 Wintermeyer, W., 126 Wintersberger, K., 2 10 Wipple, E. B., 60 Wittig, G., 63 Woenckhaus, O., 135 Wolf, F. J., 138 Wolf, H., 278 Wolf. R.. 35. 36. 253, 260. 264, 271 ' ' . Wolfe, R. S., 149 Wolfsberger, W., 184, 208 Wong, D. Y., 82 Wong, L. T. L., 29, 64, 264 Wong, S. C. K., 287 Wong, S. K., 230, 276 Woodruff. H. B.. 138 Woods, M.,55, 259 Wright, A., 136 Wright, C. H., 18 Wright, J. J., 158 Wright, S., 178 Wulff, K., 145, 278 Wunsch, G., 210 Wurmb, R., 218, 221 Wyckoff, H. W., 126 Wykle, R. L., 146 ,

,

'

Yakovlev, I. I., 290 Yakubovich, A. Ya., 224 Yakubovich, V. S., 224 Yamabe, T., 291 Yamaguchi, I., 254 Yamamoto, H., 170, 173 Yamashita, M., 34, 76 Yamazaki, A., 130 Yankowski, A. W., 2, 249 Yastre'ova, G. E., 283 Yasuda, N., 231 Yates, D. W., 146 Yatsimirskii, K. B., 204 Yee, K. C., 88, 232, 261 Ykman, P., 163 Yoneda, S., 166, 167 Yong, K. S., 64 Yoshida, Z., 166, 167 Yoshikawa, M., 133 Yoshikoshi, A., 157 Yoshimura, J., 185 Yotsui, Y., 123, 137 Young, J. M., 141 Young, J. W., 181 Youssefyeh, R. D., 181 Yow, H., 273 Yurcenko, R. I., 207 Yurzhenko, T. I., 206 Zachau, H. G., 126 Zaitseva, E. L., 224 Zayed, M. F., 37, 77, 81 Zbiral, E., 17. 24, 184, 185, 204, 255, 267 Zeck, O., 222 Zeiss, W., 248 Zelawski, Z. S., 173 Zemlicka. J.. 131 Zentil, M'., 278 Zhdanov, Y. A., 143, 178 Zhendarova, S. M., 129 Zhivukhin, S. M., 21 1, 225 Zhmurova, I. N., 191, 205, 207 Zhungietu, G. I., 26 Zhuraleva, L. P., 61, 289 Ziehn, K. D., 10, 86 Zimmer, H., 183, 204 Zimmermann, D., 87, 261 Zimmermann, M., 168 Zingaro, R. A., 235, 269 Zinov'ev, Yu. M., 45 Ziondrou, C., 103 Zoer, H., 226 Zola, M. I., 61 Zon, G., 64 Zountsas, G., 181 Zozula, V. D., 292 Zuckerman, J. J . , 3 Zwierzak, A., 96, 99, 268 Zykova, T. V., 44, 69, 70, 249