Organophosphorus Chemistry (SPR Organophosphorus Chemistry (RSC)) (v. 8)

A Specialist Periodical Report Organophosphorus Chemistry Volume 8 A Review of the Literature published between July ...

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A Specialist Periodical Report

Organophosphorus Chemistry Volume 8

A Review of the Literature published between July 1975 and June 1976

Senior Reporter S. Trippett, Department of Chemistry, University of Leicester Reporters D. W. Allen, Shefield Polytechnic R. S. Davidson, University of Leicester R. S. Edmundson, University of Bradford J. B. Hobbs, Max Planck lnstitut fiir Experimenfelle Medizin, Gottingen, W, Germany D. W. Hutchinson, University of Warwick R. Keat, University of Glasgow J. A. Miller, University of Dundee D. J. H. Smith, University of Leicester J. C. T e b by, North Stafordshire Polytechnic, Stoke-on- Trent B. J. Walker, Queen’s University of Belfast

0 Copyright 1977

The Chemical Society Burlington House, London, WIV OBN

ISBN : 0 85186 076 1

ISSN : 0306-0713 Library of Congress Catalog Card

No. 73-268317

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

Foreword

The volume of published work in organophosphorus chemistry has again increased, and several Reporters have had great difficulty in keeping within their allotted space. Much, but not all, of the research has been of a routine and predictable nature. The stimulus provided by the discovery of phosphonomycin is still being felt. It would be interesting to know just how many research projects and proposals have been linked, however tenuously, to this phosphorus-containing antibiotic. Six-co-ordinate species are being identified more frequentIy. Some are remarkably stable and have been isolated, whereas the intermediacy of others in reactions has been inferred from kinetic data. Clearly, much more will be heard of these. Finally, on the instrumental front, Fourier-transform 31Pn.m.r. spectroscopy is proving to be a very powerful tool for the detection and study of unstable intermediates, for example in Arbusov reactions, and one can look forward to the solution of many long-standing problems in organophosphorus chemistry using this technique. We hope to report on some of these in Volume 9. S.Trippett

Contents

Chapter 1 Phosphines and Phosphonium Salts By D, W. Allen

1

1 Phosphines Preparation From Halogenophosphine and Organometallic Reagents From Metallated Phosphines By Addition of P-H to Unsaturated Compounds By Reduction Miscellaneous Reactions Nucleophilic Attack at Carbon Carbonyls Miscellaneous Nucleophilic Attack at Halogen Nucleophilic Attack at Other Atoms Miscellaneous

1 1 1 2 5 6 8 10

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

18 18 21 21 23 25

3 Phospholes

27

4 Phosphorins

29

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippetf

10 10 11 12 15 17

31

1 Introduction

31

2 Structure and Bonding

32

3 Acyclic Systems

33

vi

Contents

4 Four-membered Rings

35

5 Five-membered Rings Phospholens 1,2-Oxaphospholans 1,3,2-Dioxaphospholans 1,3,2-Dioxaphospholens 1,3,2-Oxazaphospholidines Miscellaneous

36 36 37 37 39 41 44

6 Six-membered Rings

46

7 Six-co-ordinate Species

46

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

50

1 Halogenophosphines Physical and Structural Aspects Preparation Reactions with Simple Alkenes and Aromatic Compounds Reactions in which Phosphorus is Electrophilic Biphilic Reactions Miscellaneous Reactions Silyl- and Related Phosphines

50 50 51 52 53 54 58 59

2 Halogenophosphoranes Physical and Structural Aspects Preparation of Phosphoranes from Phosphorus(rI1) Compounds Preparation of Phosphoranes by Exchange Methods Reactions of Phosphoranes Synthetic Uses of Phosphine-Halogenocarbon Reactions Miscellaneous

61 61

Chapter 4 Phosphine Oxides and Sulphides By J. A. Miller

62 64 65 68 70

71

1 Preparative Aspects

71

2 Addition Reactions of R,P(X)H

76

3 Reactions involving P-C Bond Cleavage

78

4 Reactioirs at X in the P=X Group

79

vii

Contents

5 Reactions of the Side-chain

80

6 Miscellaneous Physical and Structural Aspects

a2

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker

84

1 Introduction

84

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

84 84 84 86 91 92 93 95 97 98 99

3 Phosphonous and Phosphinous Acids and their Derivatives

Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson 1 Synthetic Methods

General Phosphoric Acid and its Derivatives Phosphonic and Phosphinic Acids and their Derivatives

100

102

102 102 104 109

2 Reactions General Reactions of Phosphoric Acid and its Derivatives Reactions of Phosphonic and Phosphinic Acid Derivatives

114 114 117 124

3 Structure

131

Chapter 7 Phosphates and Phosphonates of Biochemical Interest 133 By D. W, Hutchinson 1 Introduction

133

Contents

viii 2 Coenzymes and Cofactors Nicotinamide Nucleotides Flavin Coenzymes Pyridoxal Phosphate Thiamine Phosphates

134 134 135 135 137

3 Sugar Phosphates

137

4 Phospholipids

141

5 Phosphonates

142

6 Oxidative Phosphorylation

143

7 Enzymology Enzyme Mechanisms Miscellaneous Enzymes Phosphoproteins

144 144 146 147

8 Other Compounds of Biochemical Interest

147

Chapter 8 Nucleotides and Nucleic Acids By J. B. Hobbs

151

1 Introduction

151

2 Mononucleotides Chemical Synthesis Cyclic Nucleotides Affinity Chromatography

151 151 158 159

3 Nucleoside Polyphosphates Chemical Synthesis Affinity Labelling Prebiotic Models

1 60 160 165 167

4 OIigo- and Poly-nucleotides Chemical Synthesis Enzymatic Synthesis Sequencing

168 168 171 173

5 Analytical Techniques and Physical Methods Separation and Quantitation Structure Probes

174 1 74 176

Contents

ix

Chapter 9 Ylides and Related Compounds By 0.J. H.Smith

177

1 Methylenephosphoranes Preparation Structure Reactions Aldehydes Ketones Other Carbonyl Compounds Organometallics Miscellaneous

177 177 179 179 179 181 183 184 186

2 Phosphoranes of Special Interest

187

3 Selected Applications of Ylides in Synthesis Heterocycles Pheromones Prostaglandins Carbohydrates Carotenoids Non-Benzenoid Aromatic Compounds

190

4 Selected Applications of Phosphonate Carbanions General Natural Products

199 199 202

Chapter 10 Phosphazenes By R. Keat

190 193 194 195 196 198

204

1 Introduction

204

2 Synthesis of Acyclic Phosphazenes From Amines and Phosphorus(v) Halides From Azides and Phosphorus(n1) Compounds Other Methods

204 204 206 208

3 Properties of Acyclic Phosphazenes Halogeno-derivatives Amino-, Alkyl, and Aryl derivatives

213 213 214

4 Synthesis of Cyclic Phosphazenes

219

Contents

X

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

220 220 221 223 227

6 Polymeric Phosphazenes

227

7 Phosphazenes as Fire Retardants

229

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

230

Chapter 11 Photochemical, Radical, and Deoxygenation Reactions 232 By R. S. Davidson 1 Photochemical Reactions

232

2 Phosphinidenes and Related Species

233

3 Radical Reactions

234

4 Deoxygenation and Desulphurization Reactions

240

5 Deselenation Reactions

247

Chapter 12 Physical Methods By J. C,Tebby 1 Nuclear Magnetic Resonance Spectroscopy Biological Applications Chemical Shifts and Shielding Effects Phosphorus-31 8p of PI compounds SP of PI11 compounds 8p of PIv compounds SP of P V and PVI compounds Carbon-13 Hydrogen-1 Studies of Equilibria and Shift Reagents Pseudorotation Non-equivalence,Inversion, and Medium Effects

248

248 248 249 249 249 250 250 252 252 253 253 254 255

xi

Contents

Spin-Spin Coupling JPPand JPM JPC

JPC,H JPNH

JPXCH N.Q.R. Studies

255 256 257 258 259 259 259

2 Electron Spin Resonance Spectroscopy

260

3 Vibrational Spectroscopy Band Assignment and Structure Elucidation StereochemicalAspects Studies of Bonding

262 262 263 264

4 Microwave Spectroscopy

264

5 Electronic Spectroscopy Absorption Photoelectron

264 264 265

6 Rotation

266

7 Diffraction X-Ray Electron

266 266 269

8 Dipole Moments, Permittivity, and Polarography

269

9 Mass Spectrometry

271

10 pKa and Thermochemical Studies

272

11 Chromatography and Surface Properties G.1.c. T.1.c. Paper Chromatography Column Chromatography

274 274 274 214 274

Author Index

276

Abbreviations

ADP AIBN AMP ATP CMP DBN DBU DCC DMF DMSO FAD GDP g.1.c. HMPT HMT NAD NADP NBS NMN n.q.r. PPi TCNE TDAP TFAA THF t.1.c. TMPT UDPGal UDPGlc

adenosine 5’-pyrophosphate bisazoisobutyronitrile adenosine 5’-phosphate adenosine 5’-triphosphate cytidine 5’-phosphate

1,5-diazabicyclo[4,3,O]non-5-ene 1,5-diazabicyclo[5,4,O]undec-5-ene dicyclohexylcarbodi-imide NN-dimethylformamide dimethyl sulphoxide flavin-adenine dinucleotide guanosine 5‘-pyrophosphate gas-liqu id chromatography hexamethylphosphoric triamide hexamethylenetetramine nicotinamideadenine dinucleotide nicot inamideadenine dinucleotide phosphate N-bromosuccinimide nicotinamide mononucleotide nuclear quadrupole resonance inorganic pyrophosphate tetracyanoethylene tris(dimethy1amino)phosphine trifluoroacetic acid tetr ahydrofuran thin-layer chromatography trimethylphosphoric triamide uridine 5’-pyrophosphate galactose uridine 5’-pyrophosphate glucose

t BY D. W. ALLEN

1 Phosphines Preparation.-From Halogenophosphine and Organometallic Reagents. The cyclopentadienylphosphines (1) have been obtained from the reaction of cyclopentadienylthallium with chlorophosphines in ether.l Diphenyl(4-pyridy1)phosphine (2) is prepared from 4-pyridyl-lithium and chlorodiphenylphosphine,2and an improved procedure for the synthesisof tri-(2-pyridyl)phosphine (3) from 2-pyridyl-lithium and phosphorus trichloride has been reported.a

PlpR3-n NSPPh,

(1) R = MeorPh; n = 1 or2

(3)

Treatment of phosphorus trichloride with an excess of the Grignard reagent (4) leads to the sterically hindered phosphine (5).4 A sample of 14C-labelledtriethylphosphine has been synthesized from 14C-labelledethylmagnesium iodide and phosphorus trichloride.6 The reaction of chlarodiphenylphosphine with the Grignard

reagent derived from 2,2’-dibromobibenzyl in THF solution leads to the diphosphine (6),which is dehydrogenated by various rhodium complexes to form trans-2,2’diphenylphosphinostilbene (7).6 1 3 4

5 6

F. Mathey and J.-P. Lampin, Tetrahedron, 1975,31,2685. M. A. Weiner and P. Schwartz, Inorg. Chem., 1975,14, 1714. R. K. Boggess and D. A. Zatko, J. Coordination Chem., 1975,4,217. B. I. Stepanov, A. I. Bokanov, A. B. Kudryavtsev, and Yu. G. Plyashkevich, J. Gen. Chem. (U.S.S.R.), 1975,44, 2312. M. Kanska and S. Drabarek, Nukleonika, 1974, 19,977 (Chem. Abs., 1975,83, 10270). M. A. Bennett, and P. W. Clark, J. Organometallic Chem., 1976,110, 367.

1

Organophosphorus Chemistry

2

.(i) RhI complexes (ii) NaCN ' ~

The reaction of halogenophosphines with esters of trialkylstannylacetic acids gives grouping. Diphosphinoacetic acid esters (8) can be prepared from the monophosphino-esters by treatment with sodium and dialkylchlorophosphines.*

a general route to compounds containing the -P(CH,CO,R)n

From Metallated Phosphines. The synthesis of polymeric tertiary phosphines based on the reaction of lithium diphenylphosphide with chloromethylated polystyrenes continues to attract interest. lo Considerable breakdown of the carbon-carbon back-bone of PVC occurs on reaction with lithium diphenylphosphide in THF, and only oligomers of low molecular weight resulf.ll The potassium salt (9) reacts with chloromethylated polystyrene to form the polymeric diphosphine (lO).la g3

CH,PPh,

/

The cu-chloroalkyldiphenylphosphines(1 1) have been prepared by the reaction of equimolar quantities of sodium diphenylphosphide with ao-dichloroalkanes, Whereas the phosphine (11 ;n = 3) can be converted into the Grignard reagent (12), which reacts with dimethylchlorophosphine to form the unsymmetrical diphosphine (1 3), the Grignard reagent (14) undergoes a B-elimination reaction to regenerate diphenylphosphide i011.l~ M. A. Kakli, G. M. Gray, E. G. Delmar, and R. C. Taylor, Synth. React. Inorg. Metal-Org. Chem., 1975,5, 357. 8 Z . S . Novikova, S. Ya. Skorobogatova, and 1. F. Lutsenko, Russ, P. 497307 (Chem. Abs., 1976, 84, 122038). 9 E. Bayer and V. Schurig, Angew. Chem. Internat. Edn., 1975, 14, 493. lo J. Basset, R. Mutin, G. Descotes, and D. Sinou, Compt. rend., 1975, 280, C , 1181. 11 K. A. Abdulla, N. P. Allen, A. H. Badran, R. P. Burns, J. Dwyer, C. A. McAuliffe, and N. D. A. Toma, Chem. and Ind., 1976, 273. 19 I. Tkatchenko, Compt. rend., 1976,282, C , 229. S. 0. Grim and R. C. Barth, J . Organometnllic Chem., 1975, 94, 327. 7

Phosphines and Phosphonium Salts

3

(11) II = 1-3

n

Yh,P~CHH,-CH,-MgC1

--+

Ph,@ + C,H,

+

[MgCl]’

(14)

Similarly, the chloroalkylarsine(1 5 ) (obtained from lithium diphenylarsenide and 1,Zdichloroethane) reacts with lithium diphenylphosphide to form the mixed phosphine-arsine (16).14 Ph,AsCH2CII,C1

Ph,PLi

*

(15)

Ph, AsCH,CH,PPh,

(16)

Organosilylphosphines are conveniently prepared by cleavage of alkyldiarylphosphines with lithium in THF, followed by treatment with chlorotrimethylsilane,15 and tris(trimethylsily1)phosphine has been prepared from the reaction of chlorotrimethylsilanewith a mixture of sodium and potassium phosphides.ls The product of the reaction between lithium diphenylphosphide (or trimethylsilyldiphenylphosphine)and dimethyl 2,3-dichloromaleate has been shown to be the fumarate (17) l7 and not (as previously supposed)l 8 the expected maleate (1 8).

(17)

(18)

Nucleophilic displacement of halide ion from a saturated carbon atom by alkalimetal diphenylphosphide reagents occurs with inversion of configuration at carbon, as is found in normal sN2 displacements.lBThus menthyl chloride or bromide gives the neo-menthyldiphenylphosphine (1 9). An improved procedure has been reported for the synthesis of the C-functionalized tertiary phosphine (20), based on the reaction of potassium diphenylphosphidewith ethyl chloroacetate.20 K. K. Chow and C. A. McAuliffe, Inorg. Chim. Acta, 1975, 14, 5. R. Appel and K. Geisler, J. Organometallic Chem., 1976, 112, 61. 16 G. Becker and W. Hoelderich, Chem. Ber., 1975,108,2484. 1 7 D. Fenske and J. Lons, Chem. Ber., 1975,108,3091. 18 H. J. Becher, D. Fenske, and E. Langer, Chem. Ber., 1973, 106, 177. 19 A. M. Aguiar, C. J. Morrow, J. D. Morrison, R. E. Burnett, W. F. Masler, and N. S. Bhacca, J, Org. Chem., 1976,41, 1545. 80 T. Jarolim and J. Podlahova, J. Znorg. Nuclear Chern., 1976, 38, 125. 14

15

Organophosphorus Chemistry

4

ClCH,CO,Et

Ph,PK

Ph,PCH,CO,Et

(i) OH-

Ph,PCH,CO,II

(20)

Two reports of the hitherto little documented attack of organophosphide anions on halogen have appeared. Addition of 1,Zdibromoalkenes to lithium diphenylphosphide in THF gives an acetylene and tetraphenyldiphosphine21 (Scheme 1).

- fBr-C=C-Br 'u p&P-+

I 1 R R

0 -+ R C E C R + Ph,PBr

PhzF

Ph,PPPh,

(R = H or Ph) Scheme 1

In the corresponding reactions of o-dihalogenobenzenes, attack on halogen, leading to the generation of benzyne, competes with attack at carbon, leading to the a-halogenophenyldiphenylphosphine (21). Further attack of phosphide on the halogen of the latter gives the anion (22), which on treatment with D,O gives the ortho-deuterated phosphine (23) (Scheme 2). Lithium diphenylphosphidereacts with the benzynefuran adduct (24) to give, after dehydration, a mixture of 1- and 2diphenylphosphinonaphthalenes.22

attackon +

(21) Reagents: i, PhaP-; ii, furan; iii, DaO

Scheme 2 a1 22

D. G. Gillespie and B. J. Walker, Tetrahedron Letters, 1975, 4709. D. G. Gillespie, B. J. Walker, D. Stevens, and C. A. McAuliffe, TetrahedronLetters, 1976, 1905.

Phosphines and Phosphonium Salts

5

By Addition ofP-H to Unsaturated Compounds.This route continues to be exploited for the synthesis of polydentate tertiary phosphine ligands. Thus base-catalysed addition of diphenylvinylphosphine to the secondary phosphine (25) affords (26).23 Neopentylpolytertiaryphosphines, e.g. (27), have been similarly prepared 24 by addition of primary or secondary phosphines to vinylphosphines (or the related phosphine sulphides, followed by a desulphurization step). Me,PCH,CH,P(H) Ph

+

Ph,PCH=CH,

--+

Me,PCII,CH,P(Ph) CH,CH,l’l’h,

(25)

(26) S

11 ,CH=CH,

(Me3CC€1,),PH + Me3CCH,P,

(3 KOBut (ij) Na f.

CH=CH,

/

CH2CH2P(C€1,CMe3),

Me3CCH2P

\CH,CH,I’(CH,CMe,

!,

(27)

Free-radical-catalysed additions have also been reported, and provide a genuine alternative to the more familiar base-catalysed addition routes. Thus the secondary diphosphine (28) readily adds to diphenylvinylphosphinein the presence of AIBN to give (29).2sSimilarly, addition of di(pentafluoropheny1)phosphine to diphenylvinylphosphine affords26 the diphosphine (30). Sequential addition of silanes and secondary phosphines to terminal cto-dienes under the influence of U.V. light affords the silylalkylphosphines (31), which may be anchored via silicon to the surface of inorganic oxides and used as polymeric catalysts.27 PhP(H) (CHz)3P(€~) Ph

+ Ph,PCH=CH,

(28)

AIBN

.

+.

Ph,PCH,CH,P(Ph) (CH,),P(Ph) CII,CH,PPh, (29)

Ph,PCH,CH,P(C, F5)2 (30)

(31) n = 1-4

Addition of P-H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones.28 The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35).”9 30 The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienoneto give 23 24

26

26

27

29

3O

R. B. King, J. A. Zinich, and J. C.Cloyd, jun., Inarg. Chem., 1975,14,1554. R. B. King, J. C. Cloyd, jun., and R. H. Reimann, J. Org. Chem., 1976,41,972. D. L. Dubois, W. H. Meyers, and D. W. Meek, J.C.S. Dalton, 1975, 1011. I. Macleod, L. Manojlovid-Muir, D. Millington, K. W. Muir, D . W. A. Sharp, and R. Walker, J. Organometallic Chem., 1975,97, C7. A. A. Oswald, L. L. Murrel, and L. J. Boucher, Preprints Div. Petrol. Chem., Amer. Chem. SOC., 1974,19,155, 162 (Chem. Abs., 1975,83,198225, 1976,84,105 685). I. N . Azerbaev, B. M. Butin, and Y.G. Bosyakov, J. Gen. Chem. (U.S.S.R.),1975,45, 1696. H.0.Berger and H. Noeth, Z . Naturforsch., 1975,30b, 641. G. Markl, D. Matthes, A. Donaubauer, and H. Baier, Tetrahedron Letters, 1975, 3171.

Organophosphorus Chemistry

6 Me0,C

9

C0,Me

I MeCH

CHMe

C0,Me

Me&

KONa+

(i) hydrolysis (ii) -CO,

Me

+

Ph

(33)

R2 R' M

/c-cR2

PhPH:

/-=I

R'M

PPh

both synthe phosphinone (36) has been studied.31Contrary to an earlier and anti-isomers are formed. By Reduction. The first known compounds containing a tervalent phosphorus function and an epoxide ring [(37) and (38)] have been prepared by reduction with phenylsilane of the corresponding phosphine oxides; they are quite stable, showing no

(37) (38) tendency to undergo oxygen transfer to phosphorus, and can be distilled in V ~ C U O The phosphinylacetonitriles (39) undergo selective reduction to the Corresponding phosphinoacetonitriles (40) on treatment with diphenyl~ilane.~~ 0 R,POEt

CICH,CN

+.

II

R,PCH,CN

Ph,SiH2

+ RzPCH,CN (40)

(39)

(K = Et, Pr', But, or Ph)

The isomeric bicyclic phosphines (41) have been obtained by reduction with trichlorosilaneof the related isomeric phosphine oxides, the reaction proceeding with

(41a) 31 32 33 34

(4 1b)

J. R. Wiseman and H. 0. Krabbenhoft, J. Org. Chem., 1976,41, 589. Y. Kashman and E. Benary, Tetrahedron, 1972,28, 4091. C. Symmes,jun. and L. D. Quin, Tetrahedron Letters, 1976, 1853. 0. Dahl and F. K. Jensen, Acta Chem. Scand. ( B ) , 1975,29, 863.

. ~ ~

Phosphines and Phosphonium Salts

7

retention of onf figuration.^^ In contrast, reduction with trichlorosilane of the pure cis- or trans-diazaphospholine oxides (42) gives mixtures of the cis- and transphosphines (43). The lack of stereospecificity is attributed to pseudorotation of phosphorane intermediate^.^^

The A3-phospholen sulphides (44), bearing reactive functional groups, may be reduced to the phosphine using nickelocene in the presence of ally1 iodide.37The intermediate nickel complex is decomposed with cyanide to free the functionalized A3-phospholen (45).

ex

Me

Me Me

Me

Cp,Ni CH,=CHCH,I

~

/ Ph

(44)

/"t

I

PR,

0kh

(45)

-

[X = PhCH(OH), COPh, or C02Et]

A cautionary note has appeared concerning the use of sodium bis(2-methoxyethoxy)aluminium hydride as a reducing agent in phosphorus chemistry. The use of this reagent is severely limited by the enhanced alkylating ability of the ether groups. Thus the reduction of chlorodiphenylphosphine gives a mixture of diphenylphosphine, methyldiphenylphosphine, and 2-hydroxyethyldiphenylpho~phine.~~ Lithium aluminium hydride has been employed in the reduction of the a-phosphinylalkyldiorganostannanes (46) to the phosphines (47), which are useful precursors for the synthesis of heterocyclic compounds containing both tin and phosphorus as ring members.39

(46) (R' = Et or Bu; R2 = EtO or Ph; n = 2or3; X = C l o r B r ) s5

s6 37

38 39

(47) (R' = Et or Ph; R2 = H or Ph; n = 2 or 3)

C. Symmes, jun. and L. D. Quin, J. Org. Chem., 1976, 41, 238. G. Baccolini and P. E. Todesco, J. Org. Chem., 1975, 40,2318. F. Mathey and G. Sennyey, J. Organometallic Chem., 1976,105,13. M. J. Gallagher and G. Pollard, Phosphorus, 1975, 6, 61. H. Weichmann and A. Tzschach, J. Organometallic Chem., 1975, 99, 61.

8

Organophosphorus Chemistry

Miscellaneous. A number of reports of the synthesis of unusual heterocyclic phosphines have appeared. Improved procedures for the synthesis of 1,3,5-triaza-7phospha-adamantane (48) have been r e p ~ r t e d41, ~and ~ ~ the triazaphosphahomoadamantane (49) has also been prepared.42Routes to the large ring phosphacycloalkanes (50) have been described,43and the bicyclic diphosphine (51) has been isolated from the reaction of white phosphorus with o-dichlorobenzene in the presence of transition-metal halidesag4

6;n

N+N

(50)

(R = Ph or PhCH,; n = 3 or 4)

(51)

The heterocyclic acylphosphines (52)and (53) have been prepared by the reaction of phenylbis(trimethylsily1)phosphine with the acid chlorides derived from phthalic and diphenic acids. The reaction of 2,3-dichloromaleic anhydride or thioanhydride with phenylbis(trimethylsily1)phosphine gives derivatives of the 1,4-dihydro-pdiphosphorin system (54).46

0 (5 2)

Ph (5 3)

0 (54)

Ph

0

(X = 0 or S)

&Addition of alkyl cuprate reagents to alkynyl-phosphines occurs to give the vinylphosphines (55).48 40 41 *2 43

44 45

D. J. Daigle and A. B. Pepperman, jun., J. Heterocyclic Chem., 1975, 12, 579. E. Fluck and J. E. Foerster, Chem.-Ztg., 1975, 99, 246 (Chem. Abs., 1975, 83, 97dfi77). D. J. Daigle and A. B. Pepperman, jun., J. Chem. and Eng. Data, 1975, 20, 448. L. Horner, H. Kunz, and P. Walach, Phosphorus, 1975, 6, 63. K. G. Weinberg, J. Org. Chem., 1975, 40,3586. D. Fenske, E. Langer, M. Heymann, and H. J. Becher, Chem. Ber., 1976,109, 35 J. Meijer, H. Westmijze, and P. Vermeer, Rec. Trav. chim., 1976, 95, 102.

.

9

Phosphines and Phosphonium Salts R' R'C

CPPh,

\

(i) R:CuMgX or R'CuBrMgX

(ii) ti+

R' = H o r Me; Rz = Me, Et, Pri, or But The alkynylphosphine (56)reacts with Wilkinson's catalyst to give an intermediate rhodium complex, which, when treated with diphenylacetylene followed by cyanide ion, yields the diphosphine (57), of interest as a rigid chelating ligand of fixed ge~rnetry.~

ti) (Ph,P),RhCl (ii) P h C 3 C P h (iii) CN-

Convenient routes to several new sterically crowded chelating diphosphines have been d e s ~ r i b e d . ~ *Thus, - ~ ~ e.g., rn-xylylene dibromide, on treatment with di-tbutylphosphine,affords a bisphosphonium salt, which on treatment with a weak base affords the diphosphine (58).48 CH,$(H)

Bd Br-

CH,PBU:

acetone

CII,$(H) B< Br-

NaoAc*

CH,PBI~

Rhodium and iridium complexes effect the dehydrogenationof the alkane chain in 1,6-bisdiphenylphosphinohexane to form (after treatment with cyanide ion) 1,6(bisdiphenylphosphino)-trans-hex-3-ene.s1 A new route to compounds claimed to contain the phosphyl P-C linkage has been d e s ~ r i b e dThus, . ~ ~ e.g., cyanogen bromide reacts with phosphine to give (59), which on treatment with isoamyl nitrite gives (60). BrCEN

47 48 49

2 1 -2 2 "C

*

H,N C

PHBr

- A~NO,

5

BrC-P

W. Winter, Angew. Chem. Internat. Edn., 1976, 15, 241. C. J. Moulton and B. L. Shaw, J.C.S. Dalton, 1976, 1020. C. J. Moulton and B. L. Shaw, J.C.S. Chem. Comm., 1976, 365.

so R. Mason, G. Scollary, B. Moyle, K. I. Hardcastle, B. L. Shaw, and C. J. Moulton, J. Organo61 62

metallic Chem., 1976,113,C49. P. W. Clark, J. Organometallic Chem., 1976,110, C13. I. S . Matveev, Khim. Tekhnol. (Kiev), 1974, 49 (Chem. Abs., 1975, 83, 97470).

Organophosphorus Chemistry

10

Reactions.-Nucleophilic Attack at Carbon. (i) Carbonyls. Methyl arylglyoxylates react with trisdimethylaminophosphine(TDAP) to form cis-ccg-dimethoxycarbonylstilbene oxidess3 The initially formed zwitterion (61) reacts with a second molecule of the ester to form a trans-diphenyl-l,4,2-dioxaphospholan intermediate, which undergoes a concerted symmetry-allowed retrograde n2s n4s cycloaddition to give a carbonyl ylide, conrotatory cyclization of which leads to the cis-oxirans (62) (Scheme 3).

+

0-

ArC(0) C0,Me

Me0,C'

I -$ Ar -C-

$(NMe,),

I C0,Me

NMe, Me2N Me,NJP-O Ar CO,hfe Me0,C' 'Ar

I +!, )-

+ (Me,N),PO

0 CO,Me

(62) Reagents: i, (MezN)3P; ii, ArC(0)COaMe

Scheme 3

The 'K-region'-oxirans (63) and (64), of interest in studies of chemical carcinogenesis, have been prepared by cyclization with TDAP of the dialdehydes obtained by oxidative cleavage of the parent hydrocarbon~.~~

The reaction of the phospholen (65) with aromatic acid chlorides in the presence of triethylamine, followed by addition of D20, gives a ready route to aromatic [1-2H]aldehydes with 100% incorporation of d e u t e r i ~ m . ~ ~

53 54 55

G. W. Griffin, D. M. Gibson, and K. Ishikawa, J.C.S. Cliem. Comm., 1975, 595. R . G. Harvey, Swee Hock Goh, and C . Cortez, J. Amer. Chem. SOC.,1975,97, 3468. C . A. Scott, D. G . Smith, and D. J. H. Smith, Synrh. Comm., 1976, 6 , 135.

Phosphines and Phosphonium Salts

11

(ii) Miscellaneous. Nucleophilic attack of dimethylphosphine (or tetramethyldiphosphine) occurs at the terminal olefinic carbon of hexafluoropropene to give a mixture of cis-and trans-dimethylpentafluoropropenylphosphines(66) in proportions which depend on the reaction conditions.s6The products do not arise by dehydrofluorination of a 1:1 adduct.

Further evidence of anchimeric assistance between the oxygen 2p orbitals of the o-methoxyphenyl group and the 3d orbitals of the developing phosphonium centre has been obtained in studies of the rate of quaternization of the phosphine (67). However, the presence at phosphorus of ferrocenyl substituents which are capable of conjugative stabilization of the developing phosphonium centre does not lead to a marked increase in the rate of quaternization of tertiary phosphines [e.g. (68)], supporting the concept that the transition state for the s N 2 reaction of a tertiary phosphine with an alkyl halide lies closer to the reactants rather than to the products in the energy profile diagram.67 Ring opening of diphenylthiiren 1,l-dioxide58 and diphenylcyclopropenonesD occurs on reaction with tertiary phosphines to form the betaines (69) and the keten phosphoranes (70),respectively. Tertiary phosphines react with the thione (71) to form mainly the betaine (72).60 + R,P,

so;

/

Ph/c=c\

Ph

R,P=C(Ph)

-C(Ph)=C=O (70)

(69)

58 57 58 59

6o

P. Cooper, R. Fields, and R. N. Haszeldine, J.C.S. Perkin I, 1975, 702. W. E. McEwen, J. E. Fountaine, D. N. Schulz, and W.4. Shiau, J. Org. Chem., 1976,41, 1684. B. B. Jarvis, W. P. Tong, and H. L. Ammon, J. Org. Chem., 1975, 40, 3189. A. Hamada and T. Takizawa, Chem. and Pharm. Bull. (Japan), 1975,23, 2933. M. G. Miles, J. S. Wager, and J. D. Wilson, J. Org. Chem., 1975, 40, 2577.

12

Organophosphorus Chemistry

Nucleophilic Attack at Halogen. The reactions of tertiary phosphines, in particular triphenylphosphine and TDAP, with tetrahalogenomet hanes continue to attract much interest. Recent progress in understanding the course of the reactions occurring between triphenylphosphine,carbon tetrachloride, and a substrate, and the preparative applications of tertiary phosphine-carbon tetrachloride ‘reagents’, have been reviewed.s1 In reactions employing these reagents, the reactions of the substrate compete with the ‘internal’ reactions of the two-component system, so that the overall course is much more complex than previously assumed. The first isolable product in the reaction of triphenylphosphineand carbon tetrachloride is the salt (73), which reacts rapidly with further phosphine to give the stable phosphorane (74).62In contrast, tris-t-butylphosphinereacts with germanium and tin tetrahalides to form the salts (75);6s compounds of the latter type have long been postulated as arising from the reactions of phosphines with carbon tetrahalides but so far have defied detection. Ph,kCl, C1-

(7 3)

Ph,P

+

Ph,F’=CCCI, + I’h,PCI, J

*I

I’h,P

[But, ;XI MX; (75)

X = Cl or Br M = G e or Sn

[ I’llJ P =c =-PYll,]+ C1

c1-

(74)

Two routes for the reaction of substrate with the triphenylphosphine-carbon tetrachloride reagent are now 62* 64 Direct interaction (76) of the substrate with the initially formed dipolar associate leads to the formation of chloroform and the intermediate phosphonium salt (77).

Direct chlorination of the substrate by the dichlorotriphenylphosphorane present in the reaction mixture competes with the above route. The HCl liberated is taken up by the dichloromethylenetriphenylphosphorane also present to form dichloromethyltriphenylphosphonium chloride (78), which reacts further with triphenylphosphine with the eventual formation of chloromethyltriphenylphosphonium 61 62

R. Appel, Angew. Chem. Internat. Edn., 1975, 14, 801. R. Appel, F. Knoll, W. Michel, W. Morbach, H.-D. Wihler, and H. Veltmann, Chem. Ber., 1976, 109, 58.

63 64

W.-W. du Mont, B. Neudert, and H. Schumann, Angew. Chem. Internat. Edn., 1976,15, 308. 1. Tomoskozi, L. Gruber, and L. Radics, Tetrahedron Letters, 1975, 2473.

13

Phosphines and Phosphonium Salts

J

Ph, P=CM C1 \iii

1[Ph3kH,CI] C1(79) Reagents: i, PhsP; ii, PhsP=CC12; iii, HC1 Scheme 4

chloride (79) (Scheme 4). This route, which does not lead to the formation of chloroform appears to be followed to the extent of 95% in the reactions of enolizable ketones with the triphenylphosphine-carbon tetrachloride reagent.s4 The phosphonium salts (78) and (79) precipitate from the reaction mixtures. Such precipitates observed earlier in other reactions have been referred to as triphenylphosphine oxide and/or triphenylyhosphine hydrochloride without characterization.s6 In spite of the above complexity, exploitation of these reagents in synthesis continues. Thus the triphenylphosphinecarbon tetrachloride combination has been employed as a condensing agent in peptide 6 7 and the TDAP-carbon tetrachloride combination for the synthesis of halogenated and sulphonated carboh y d r a t e ~ .69 ~ ~Other , reactions reported include the use of triphenylphosphinecarbon tetrachloride to chlorinate polyfiydroxyethyl methacrylate) and poly(2hydroxypropyl metha~rylate),~ O and to convert 5‘-alkylthiocarbamates or dithiocarbamates into N-phenylchlorothioformimidates.71Arylhydroxylamines are converted by the triphenylphosphine-carbon tetrachloride reagent into a mixture of the azobenzene and corresponding az~xybenzene.’~ A full report of the reactions of the TDAP-carbon tetrachloride reagent with vicinal diols, to give either trans-epoxides or spirophosphoranes, has appeared.73 The reactions of cro-diols with TDAPcarbon tetrachloride have also been studied 74 and conditions defined for the exclusive formation of monoalkoxyphosphoniumsalts (80), which may then be subjected to a 65

s6 67

69 70

71 72

73 74

N. S. Isaacs and D. Kirkpatrick, J.C.S. Chem. Comm., 1972,443; E. Yamato and S. Sugasawa, Tetrahedron Letters, 1970, 4383; J. B. Lee and T. J. Nolan, Tetrahedron, 1967, 23, 2789. R. Appel, G. Baumer, and W. Striiver, Chem. Ber., 1975,108,2680. R. Appel, G. Baumer, and W. Striiver, Chem. Ber., 1976,109, 801. B. Castro, Y. Chaplew, and B. Gross, Bull. SOC.chim. France, 1975, 875. R.-A. Boigegrain, B. Castro, and B. Gross, Tetrahedron Letters, 1975, 3947. H. I. Cohen, J. Polymer Sci., Polymer Chem. Edn., 1975, 13, 1499. R. Appel and K. Giesen, Chem. Ber., 1976, 109, 810. T. Ohashi and R. Appel, Bull. Chem. SOC.Japan, 1975,48, 1667. R.-A. Boigegrain and B. Castro, Tetrahedron, 1976,32, 1283. R.-A. Boigegrain, B. Castro, and C. Selve, Tetrahedron Letters, 1975, 2529.

14

Organophosphorus Chemistry

range of nucleophilic displacement reactions. Alkylphosphinates (8 1) are formed in good yield by the simultaneous action of alcohols and carbon tetrachloride on chlorophosphines in the presence of an auxiliary base. 75

(80)

iI

= 4-11

(81) R',

R2,K3 = nlkyl

(82)

Applications of the combination of polymer-supported triarylphosphines (82) with carbon tetrachloride for the synthesis of peptides 7 6 and acid ~ h l o r i d e s , ~ ~ involving a simple filtration and evaporation process for product isolation, have been reported. The reactions between PP-diphosphines, carbon tetrachloride, and primary or secondary amines have been studied. In general, diaminophosphonium salts (83) are formed, except for reactions involving sterically hindered aniines, when chloromethylphosphonium salts [e.g. (84)] or methylenebisphosphonium salts [e.g. (85)l

,

[Rii' (N R2R3

1 C1-

*/ Ph,P

(83) R' = Me, Et, PIn, Bun, or 1% R2 = 11, Me, or Et R3 = Et, P r n , Pri, But, or Ph

N(Me) But

+

Me,P -CH2-

el-

\CH,Cl

1

N(Me) Ph

(84)

+

PMe,

I N(Me) Ph

2Cl'

(85)

result. The corresponding reactions of the cyclic diphosphine (86) occur either with ring opening to give (87) or with ring expansion to give (88), depending on the nature of the amine.78 The reactions of cyclopolyphosphines with carbon tetrachloride and with amine-carbon tetrachloride combinations have also been inve~tigated.~~ The rates of dehalogenation of a-bromo- and a-iodo-m-cyanobenzylphenylsulphones (89) by a number of sterically hindered phosphines in aqueous DMF have

2c1-

75

78 77 78

79

R. Appel and U. Warning, Chem. Ber., 1976,109, 805. R. Appel, W. Striiver, and L. Willms, Tetrahedron Letters, 1976, 905. P. Hodge and G. Richardson, J.C.S. Chem. Comm., 1975, 622. R. Appel and R. Milker, Chem. Ber., 1975,108, 2349. R. Appel and R. Milker, 2. anorg. Chem., 1975, 417, 161.

2c1-

Phosphines and Phosphonium Salts

2::s

R,P t X-CHS0,Ph

I

O

C

15 CH,SO,Ph + R,PO + HX

I

O

N

C

N

(89) (X = Br 0x1)

been studied. Variation in the rate data for tri-o-tolylphosphine and tri-o-anisylphosphine is best explained in terms of a steric effect rather than a special electronic effect arising from interactions of the methoxy-group with the phosphonium centre (cf: ref. 57). The use of diphosphines (e.g. 1 ,2-bisdiphenylphosphinoethane),in which a second phosphorus atom might assist in the transition state, produces no special effects. * Nucleophilic Attack at Other Atoms. The adduct (90) from triphenylphosphine and diethyl azodicarboxylate(DAD) catalyses transesterification under neutral and mild conditions (Scheme 5). C0,Et

I

C0,Et

I

.+

/co2Et CH

(90)

-

4

Ph$’+

-NCO,Et I

I

,C+:O EtO,CCH, OEt Me

I

I

11 9 M: e

C0,Et

EtOH

/

f

CH

\/+

TC0,Me

T A

/ \3

EtO,CCH,

+ (90)

OEt

Scheme 5

Unsaturated monosaccharides [e.g. (91)] react with the Ph,P-DAD combination in the presence of phthalimide, with inversion of configuration of C-4, to form the phthalimido-derivatives (92).83 Treatment of carbohydrates having a free anomeric OH group with 6-chloropurine, DAD, and methyldiphenylphosphine gives the purine nucleosides (93).s3

g2

B. B. Jarvis and B. A. Marien, J. Org. Chem., 1975, 40,2587. S. Bittner, Z. Barneis, and S. Felix, Tetrahedron Letters, 1975, 3871. A. Banaszek, B. Szechner, J. Mieczkowski, and A. Zamojski, Roczniki. Chem., 1976, 50, 105

83

(Chem. A h . , 1976, 84, 165150). W. A. Szarek, C . Depew, H. C. Jarrell, and J. K. N. Jones, J.C.S. Chem. Cornm., 1975, 648.

80

81

Organophosphorus Chemistry

16

Q

(91) R', Rz = H, OMe

eOH @Nil*; (92)

CH,OMe

Me0

CH,OMe

6-chloropuiine. Ph,PMe, DAD '

Me0

OMe-

OMe

N==/

(93)

The use of the triphenylphosphine-di(2-pyridyl) disulphide reagent for effecting condensation reactions has been reviewed.84Combination of triphenylphosphine with bis(0-thiocarbonyl) disulphide gives a superior reagent compared to that mentioned above for the preparation of mixed diesters of phosphoric acid from monophosphate esters.86 Further studies of the kinetics of reaction of disulphides with triphenylphosphine and water have been supporting the previously suggested two-step mechanism.88 The reactions of 35S-labelledacetyl aralkyl disulphides with triphenylphosphine have also been investigated.89 The adducts (94) of triphenylphosphine and alkylphenyl-N-p-tosylsulphilimines also act as dehydrating agents, and have been employed in the synthesis of acid anhydrides, esters, and amides. O, O1 R

Nso2tol-p

"SO, tol-p (94)

The diphosphine monosulphides (95) rearrange on heating, the sulphur migrating to the more basic phosphorus centre.92Benzyl methanesulphenate (96) reacts with

(95) R = Me or Ph 84

85 87

88

T. Mukaiyama, Angew. Chem. Znternat. Edn., 1976, 15, 94. H. Takaku, M. Yamana, and Y. Enoki, J. Org. Chem., 1976,41, 1261. L. E. Overman and S. T. Petty, J. Org. Chem., 1975, 40, 2779. L. E. Overman and E. M. O'Connor, J . Amer. Chem. Suc., 1976,98, 771. L. E. Overman, D. Matzinger, E. O'Connor, and J. D. Overman, J . Amer. Chern. Soc., 1974,96, 6081.

89 O0 91

92

S. Kawamura, A. Sato. T. Nakabayashi, and M. Hamada, Chern. Letters, 1975, 1231. T. Aida, N. Furukawa, and S. Oae, Chem. Letters, 1975, 29. S. Oae, T. Aida, and N. Furukawa, Chem. and Pharm. Birll. (Jupnn), 1975, 23, 301 I . S. 0. Grim and J. D. Mitchell, J.C.S. Chem. Comm., 1975, 634.

17

Phosphines and Phosphonium Salts

Bu,P=O

+ MeSCH2Ph

tributylphosphine in toluene at - 20 "Cto give benzyl methyl sulphide and tributylphosphine oxide, the reaction proceeding via an oxythiophosphorane.93 1,2,4-Dithiazol-3-ones(97) react with triphenylphosphine to give almost quantitative yields of thioacyl iso~yanates.~~

+

Miscellaneous. Oxidation of (R)-( )-methylphenylbenzylphosphine with either hydroxylamine or hydrogen peroxide in acetic acid proceeds with retention of configuration.95 The use of transition-metal complexes of chiral phosphines in the homogeneous catalysis of asymmetric synthesis has been reviewed,D6and further reports of such reactions catalysed by complexes of chiral DIOP (98) have appeared.97-100The ferrocenyldiphosphine (99) has also been used as a chiral ligand, promoting high optical yields in the rhodium-complex-catalysed asymmetric hydrogenation of a-acetamido-acrylic acids to a-amino-acids.lO1

MexO--r-CH2PPh, Me

0-CH -CH2PPh,

Oxidation by molecular oxygen of trifluoroacetyldiphenylphosphinein ether in a polythene vessel yields the compound (100),lo2previously suggested as an intermediate in the reaction of chlorodiphenylphosphinewith trifluoroacetic acid which gives (101).lo3In a glass vessel, (100) rapidly isomerizes to (101). 93

D4 95 96

97 98 99

100 lol

D. H. R. Barton, D. Manley, and D. A. Widdowson, J.C.S. Perkin I, 1975, 1568. J. Goerdeler and K. Nandi, Chem. Ber., 1975, 108, 3066. R. Luckenbach, Tetrahedron Letters, 1976, 2017. H. B. Kagan, Pure Appl. Chem., 1975,43,401. G. Gelbard, H. B. Kagan, and R. Stern, Tetrahedron, 1976,32, 233. R. Glaser, S. Geresh, and J. Blumenfeld, J. Organometallic Chem., 1976, 112, 355. C. Botteghi, Gazzetta, 1975, 105, 233. B. R. James, D. K. W. Wang, and R. F. Voigt, J.C.S. Chem. Comm., 1975, 574. T. Hayashi, T. Mise, S. Mitachi, K. Yamamoto, and M. Kumada, Tetrahedron Letters, 1976, 1133.

E. Lindler, H. D. Ebert, and H. Lesiecki, Angew. Chern. Internar. Edn., 1976, 15, 41. lo3 D. J. 14. Smith and S. Trippett, J.C.S. Perkin I , 1975, 963. Io2

Organophosphorus Chemistry

18

'PPh, (102) R = H o r M e

The diphosphines (102) undergo ready degradation to give derivatives of (103) on reaction with oxygen, methyl iodide, bromine, or acetic acid; a mechanistic scheme has been suggested.Io4 The reaction of phosphine (produced in situ from magnesium phosphide and hydrogen chloride in dioxan solution) with 1,Sdiketones gives1.OSthe phosphorinanone derivatives (104). Carbonyl conipounds and heterocumulenes (e.g. C02,CS2) insert into the germanium-phosphorus bond of germaphospholans to form derivatives of the germaphosphepin system [e.g. (105)].1069 lo7

2 Phosphonium Salts Preparation.-The hydroxyalkylphosphines (106) (obtained by the cleavage of THF or tetrahydropyran with lithium diorganophosphides) are converted in good yield into the cyclic phosphonium salts (107), (108) on treatment with hydrogen bromide followed by a weak base.lo8

= 2or3

105

S. M. Nelson, M. Perks, and B. J. Walker, J.C.S. Perkin I , 1976, 1205. V. I. Vysotskii, E. V. Pavlycheva, and M. N. Tilichenko, J. Gen. Chem. (U.S.S.R.),1975, 45,

lo6 1°7 108

C. Couret, J. Escudie, J. Satge, and G . Redoules, J. Organometallic Chem., 1975, 94, C35. C. Couret, J. Escudie, J. Satge, and G . Redoules, J. Organometallic Chem., 1976, 111, 263. W. R. Purdum and K. D. Berlin, J . Org. Chem., 1975, 40, 2801.

104

1434.

Phosphines and Phosphoniiirn Salts

19

The intramolecular cyclization of propenyl or allylphosphonium salts [e.g. (log)] to phosphinolinium or isophosphinolinium salts [e.g. (1 lo)] by polyphosphoric acid (PPA) has been to proceed via a cation-alkylation mechanism, as suggested in the original report.l1°

Quinolylmethylphosphonium salts (111) can be prepared directly from the reaction of triphenylphosphine with 2-methylquinolines and iodine,lll and the reaction of 5-chloromethyluracil with triphenylphosphine gives 112 the salt (112). Both salts behave normally in olefination reactions.

The reaction of triphenylphosphine with 2-acylamino-2-(chloro)acetophenones gives the salts (113), which may be cyclized to the oxazolylphosphonium salts (114).l13 Similarly, the halogenocarboxamides (115) react readily with triphenylphosphine to give the enamide phosphonium salts (1 16), which on treatment with primary or secondary mines give the salts (117).l14 PhC(0) CH(C1) NH.C(O) R

R = Me, E t, Prn,or Ar

ph3p+

Ph&CH-NH

C1'

I 1 PhCO C(0)R

.m+p h 3 i h K J R

c1-

(1 14)

W. R. Purdum, G. A. Dilbeck, and K. D. Berlin, J. Org. Chem., 1975,40, 3763. G. A. Dilbeck, D. L. Morris, and K. D. Berlin, J. Org. Chem., 1975, 40, 1150. ll1 I. N. Chernyuk, V. V. Shelest, M. Yu. Kornilov, and G. T. Pilyugin, J. Gen. Chem. (U.S.S.R.),

lo9 110

1975,45, 1525.

R. A. Sharma and M. Bobek, J. Org. Chem., 1975,40,2377. 113 B. S. Drach, I. Y.Dolgushina, and A. D. Sinitsa, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1229. l14 B. S. Drach, E. P. Sviridov, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1975, 45, 10. 118

20

Organophosphorus Chemistry

Tertiary arylphosphines react with 2,4-dinitrochlorobenzeneto form the salts (118) in good yield under mild conditions.*ls Trimethylphosphine reacts with trimethylsilylcobalt tetracarbonyl to form the silylphosphonium salt (1 19); such compounds are rather unstable, decomposing immediately in air.116The reaction of tertiary phosphines with iodomethyltrimethyltin initially forms the unstable salts (120), which rapidly decompose to ylides. Subsequently, transylidation reactions lead to the eventual isolation of methylphosphonium ~a1ts.l~' + [ Me,Si-PMe,]

[Co(CO>,]'

(119) (118) Ar = Ph or p-tol.

Alkylation of carbonyl-stabilized ylides gives alkoxyvinylphosphoniumsalts (121), which are reported118to rearrange to the ketophosphonium salts (122). In contrast, the thioalkylvinylphosphonium salts (123) appear to be ~tab1e.l'~ 0

It R,P=CHCR'

+

R'I, Ph,P-CH=C

7

0

I-

_ _ f

Ph,i-CH(R2)CR'

ll

I-

R' = Me or Ph; Rz = Me or PhCH, S

PIi,P=

"

CHCIR'

R' = SMe

-%

PII,~-CH=C,

I' 'S R2

Phosphonium salts, e.g. (124), derived from polynuclear hydrocarbons and used as intermediates in helicine synthesis, have been prepared by the reaction of the appropriate benzylic alcohol with triphenylphosphine hydrobromide.12* Similarly, the salt (125), of value as an intermediate in carotenoid synthesis, has been prepared by the reaction of a precursor allylic alcohol with triphenylphosphine hydrobrornide.l2l Bromomethyl or-diketones react with triphenylphosphine to form B. V. Timokhin, L. V. Mironova, andV. I. Glukhikh, J. Gen. Chem. (U.S.S.R.),1975,45,2508 H. Schiifer and A. G. MacDiarmid, Inorg. Chem., 1976,15, 848. R. L. Keiter and E. W. Abel, J . Organometallic Chem., 1976, 107, 73. 118 A. Nesmeyanov, S. T. Berman, and 0. A. Reutov, Zzvest. Akad. Nauk S.S.S.R., Ser. khim., 1975,2845 (Chem. Abs., 1976,84,90227). llDH. Yoshida, H. Matsuura, T. Ogata, and S. Inokawa, Bull. Chem. SOC. Japan, 1975,48, 2907. 1 2 0 A. Moradpour, H. Kagan, M. Baes, G. Morren, and R. H. Martin, Tetrahedron, 1975, 31, 2139. 1 2 1 B. C. L. Weedon, B. P. 1391806 (Chem. Abs., 1975, 83, 97568). 115 116 117

Phosphines and Phosphonium Salts

21

phosphonium salts122[e.g. (126)l. The salt (127) has been prepared, and used as a new synthon for cyclopentanone synthesis, being synthetically equivalent to an a~y1zwitterion.l~~

0

Reactions.-Alkaline Hydrolysis. The first total resolution of a heterocyclic phosphonium salt containing an asymmetric phosphorus atom (128) has been reported, providing ready access to optically active phospholan derivatives of value for studies of the stereochemistry of nucleophilic displacement at phosphorus.124Alkaline hydrolysis of (128) proceeds with retention of configuration at phosphorus to form the oxide (129). Stereochemical studies in the phospholan series have also been facilitated by the X-ray in~estigationl~~ of an isomer of l-iodomethyl-l-pheny1-3methylphospholanium iodide, which is shown to have the structure (130).

Alkaline hydrolysis of methoxyphospholanium salts [e.g.(13l)] occurs with partial retention and partial inversion of configuration at phosphorus, whereas hydrolysis of the corresponding pliosphorinanium salts [e.g. (132)] occurs with complete inversion. In the phosphorane intermediates derived from the former, stereoelectronic strain (which tends to place methoxide in an apical position) and ring strain (which directs the ring to span apical-equatorial positions) are of comparable magnitude when methoxide is the leaving group. In the corresponding phosphoranes lZ2 123 lZ4

125

M. I. Shevchuk, V. N. Kushnir, V. A. Dombrovskii, M. V. Khalaturnik, and A. V. Dombrovskii, Zh. obschei Khim., 1975, 45, 1228 (Chem. Abs., 1975, 83, 131685). J. P. Marino and R. C. Landick, Tetrahedron Letters, 1975, 4531. K. L. Marsi and H. Tuinstra, J. Org. Chem., 1975, 40, 1843. A. Fitzgerald, G . D. Smith, C. N. Caughlan, K. L. Marsi, and F. B. Burns, J. Org. Chem., 1976,41, 1155.

2

22

Organophosphorus Chemistry

Me

Me

I

OH-*

(132)

(100%) inversion

derived from the phosphorinanium salts, the dominant factor is relief of stereoelectronic strain when the methoxide is placed in an apical position with the ring diequatorial.126 In the alkaline hydrolysis of (R)-( )-methyl(pheayl)(ct-naphthy1)allylphosphonium salts, the naphthyl group is cleaved with predominant retention of configuration at phosphorus, whereas the ally1 group is lost with predominant inver~i0n.l~’ Alkaline hydrolysis of the salt (133) occurs with exocyclic loss of phenyl, presumably via an oxyphosphorane in which the ring system spans diequatorial posit ions.128

+

-Me

IY

0-

(1 33)

1d -+

Ph’

\o

A full report has now appeared of solvent effects on the rates of hydrolysis of benzyltriphenylphosphonium bromide. The remarkable increase in rate in media of low polarity is largely attributable to a shift of the pre-equilibrium between phosphonium and hydroxide ions in favour of the intermediate hydroxyphosphorane.lzg In a similar vein, a study of medium and deuterium isotope effects on the rate of hydrolysis of tetraphenylphosphonium chloride in acetone-water mixtures has been lZ6 K.

L. Marsi, J. Org. Chem., 1975, 40, 1779. Luckenback, Z . Nuturfursch., 1975, 30b, 119. M. El-Deek, G. D. Macdonell, S. D. Venkataramu, and K. D. Berlin, J. Org. Chem., 1976,41, 1403. A. Schnell, J. G . Dawber, and J. C. Tebby, J.C.S. Perkin IZ, 1976, 633. F. Y.Khalil and G. Aksnes, 2.Phys. Chem. (Frankfurt), 1975,97, 179 (Chem. Abs., 1976, 84, 42 999).

lZ7R.

128

129 130

23

Phosphines and Phosphonium Salts

Aryl migration reactions in the hydrolysis of vinyl-phosphonium salts (134) continue to be studied, with particular reference to the role played by the substituent Z . When the latter is able to stabilize an adjacent carbanion (e.g. COAr,131 SR132),aryl migration from phosphorus to adjacent carbon occurs to form the rearrangement products (135), as established by earlier workers. When Z is less strongly electron-withdrawing (e.g. OR), rearrangement does not occur, and simple loss of phenyl or the vinylic substituent depending on the conditions. The previously accepted mechanism for aryl migration, involving intramolecular collapse of the phosphorane (136), has been criticized, and an alternative route involving the ylide (137) and the carbenoid phosphorane (138) suggested.132

(138)

The zwitterions (139) (formed by the reaction of the tributylphosphine-carbon disulphide adduct with acetylenic carboxylic acids) undergo hydrolysis to give 1,3dithi01es.l~~The products of alkaline hydrolysis of the salts (140) have been investigated.134

’&(’’-

“us

Bu,P+/

H

(139) R = H or CO,H

lj)

(ii)

H+ + RMcozH sxs I

OH-

R$-CHCH,Br

H

H

Br-

. OR2 (140) R’ = Ph; R2 = E t o r B u R’ = Bu; R2 = Bu

Additions to Vinylghosphoiziurn Salts. Vinyltriphenylphosphonium bromide reacts with the enolate (141) to give a one-stage synthesis of the tricyclic ketone (142) (Scheme 6).135 131 lS2 133 134 13j

M.M.Shevchuk, S. T. Shpak, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.), 1975,45, 2109. H. Christol, H. C. Christau, and M. Soleiman, Brill. SOC.chim. France, 1976, 161. C. U. Pittman, jun. and M. Narita, J.C.S. Chem. Comm., 1975, 960. R. A. Khachatryan, A. M. Torgomyan, M. Zh. Ovakimyan, and M. G. Indzhikyan, Armyon. khim. Zhur., 1975, 28, 34 (Chem. A h . , 1975, 83, 97462). R. M. Corey and D. M. T. Chan, Tetrahedron Letters, 1975, 4441.

0rganoplzosphovus Cherri istry

24

(141) + Reagents: i, Ph3PCH=CH2 Br-

Scheme 6

The use of vinylphosphonium salts in heterocyclic synthesis continues to be exploited. The kinetically controlled reactions of the @-acylvinylphosphoniumsalts (143) with 2-aminopyridine lead to the salts (144); similar reactions occur with 2-aminopyrimidine and cytosine. Under conditions where thermodynamic control prevails, the salts (145) are formed predominantly, resulting from a Dimroth rzarrangement of (lM).136 0

II

RC -CH=CFI-PPh,

+

(143) R = M e o r E t

(144)

(145)

The anion from pyrrole-2-aldehyde adds sequentially to the salt (146), resulting in the py~rolizinel~~ (147) (Scheme 7).

Reagents: i, 0

~

~

0

N -

Scheme 7 l313 137

C.Ivancsics and E. Zbiral, Annalen, 1975, 1934. V. W. Flitsch and E. R. Gesing, Tetrahedrun L e f t u s , 1976, 1997.

25

Phosphines and Phosphoniunz Salts

The reaction of a-mercaptocarbonylcompounds [e.g. (148)] with buta-l,3-dien-lyltriphenylphosphonium salts unexpectedly leads to 3-~inylthiophens,1~~ whereas reaction with vinylphosphonium salts results in the formation of cis-2,5-dialkyl-2,5dihydrothiophens (149).13

rn

+ Ph,P

R', R2,R3 =

alkyl

A number of addition reactions to the salt (150) have been reported.lP0With azide ion, the ylide (151) is formed. Diels-Alder addition of cyclopentadiene occurs to form isomeric adducts (152). With thioamides, a mixture of the salts (153) and (154) results, and with, e.g., 2-aminopyridine, the salt (155) is formed.

Miscellaneous. The reaction of the aminophosphonium salt (156) with thiols and alkoxides affords a convenient, high-yield, single-step synthesis of unsymmetrical thi0ethe1-s.~~~ The key intermediate is the alkoxyphosphonium salt (157), which undergoes nucleophilic attack by RS- at the alkoxy carbon. 138 139 140 141

J. M. McIntosh and F. P. Seguin, Canad. J. Chem., 1975, 53, 3526. J. M. McIntosh and G. M. Masse, J. Org. Chem., 1975, 40, 1294. C. Ivancsics and E. Zbiral, Monarsh., 1975, 106, 839. Y . Tanigawa, H. Kanamaru, and S. I. Murahashi, Tetruherlron Letters, 1975, 4655.

Organophosphorus Chemistry

26

The formation of p-nitro-NN-dimethylaniline(in addition to the expected p nitrophenyl ether) in the reaction of nitrophenate ion with the alkoxyphosphonium salts (158) indicates the intermediacy of the relatively stable interconverting phosphoranes (159). Loss of dimethylamide ion gives the salt (160), which subsequently undergoes SNAr reactions.142

(160)

(159)

High yields of dihydrofurans are obtained from the reaction of the cyclopropylphosphonium salt (161) with sodium ~arboxy1ates.l~~

(161)

Ar

,XR \;I/

Ar

,/

\0-menthyl

PP,

cI;co,I~

Ar

,XR \p'

Ar',

\o

(162) 143 143

I. M. Downie, H. Heaney, and G.Kemp, Tetrahedron Letters, 1975, 3951. W. G. Dauben and D. .I.Hart, Tefrahedron Letters, 1975, 4353.

Phosphines and Phosphonium Salts

27

Trifluoroacetolysis of the optically active salts (162) gives optically active phosphinate esters.144 Long-chain alkyl 146 and polymer-bound phosphonium salts have been used as phase-transfer catalysts. 145s

3 Phospholes A detailed review of the literature relating to the problem of phosphole aromaticity has appeared,148and the past year has seen the publication of several more papers on this theme. A theoretical approach, coupled with the results of photoelectron spectroscopy, confirms that phospholes (163), despite their pyramidal structure at phosphorus, are ‘aromatic’ systems. The ‘aromatic’ stabilization relative to the conjugatively interrupted cis-butadiene and PR sub-units is gained from nn* conjugative and P-C/n* hyperconjugative interactions between the sub-units. These interactions appear not to be accompanied by appreciable n-charge transfer (i.e. electron delocalization) from the PR sub-unit to the diene sub-unit, mainly due to In an alternative theostrong electron acceptance by the phosphorus 3d 0rbita1s.l~~ retical the electronic structure of phosphole itself (163; R = H) has been compared with those of furan, thiophen, and pyrrole by the non-empirical LCGO procedure. The results indicate (i) that phosphole will have a non-planar structure, (ii) that the phosphorus 3d orbitals behave as polarization functions rather than strongly bonding functions, and (iii) that phosphole has no resonance energy, the two most stable n M.O.’s being as in butadiene, suggestingat least a non-aromatic character. It is clear that phosphole is much less aromatic than other heterocyclopentadienes. The low inversion barriers measured for phospholes, previously taken to indicate delocalization of the phosphorus lone pair, can be accounted for without reference to aromatic character. In a related paper,151it is predicted that phosphole is likely to be isolated as a Diels-Alder dimer, due to its high dienic character. Theoretical studies have also been made to compare the valence ionization potentials of phosphole and pyrrole.162 5-Phenyl-dibenzophosphole (1 64) results from the reaction of tetraphenylphosphonium chloride with certain lithium dialkylamides;a free-radical mechanism

R

144 145

146 147 148 148

150

151

152

Ph

Ph,P -NR,

K. E. DeBruin and E. D. Perrin, J. Org. Chem., 1975, 40, 1523. D. Landini, A. M. Maia, F. Montanari, and F. M. Pirisi, J.C.S. Chem. Comm., 1975, 950. T. Sakakibara, M. Yamada, and R. Sudoh, J. Org. Chem., 1976, 41, 736. M. Cinouini, S. Colonna, H. Molinari, F. Montanari, and P. Tundo, J.C.S. Chem. Comm., 1976, 394. A. N. Hughes and D. Kleemola, J. Heterocyclic Chem., 1976, 13, 1. W. Schiifer, A. Schweig, and F. Mathey, J. Amer. Chem. Soc., 1976, 98, 407. M. H. Palmer and R. H. Findlay, J.C.S. Perkin II, 1975, 974. M. H. Palmer and R. H. Findlay, J.C.S. Perkin II, 1975, 1223. W. von Niessen, L. S. Cederbaum, and G. H. F. Diercksen,J . Amer. Chent. SOC.,1976,98,2066.

28

Organophosphorz~sChemistry

is suggested,lK3involving homolysis of the P-N bond of the aminophosphorane (165). Photolysis of the phosphine (166) gives the benzophosphole (167) in good yield.15* The dilithium aldimine (168) reacts with phenyldichlorophosphine to form the benzophosphazole (169).lK6

,But

The products of the reaction of the benzophosphole (170) with dimethyl acetylenedicarboxylate include the ylide (171) and the benzodihydrophosphonin (172).15s The chlorodiazaphospholine (173) readily loses hydrogen chloride, oia the phosphanylium ion (174), to form the diazophosphole (175).lK7

153 154 155 156 15'

N. A. Nesmeyanov, 0. A. Rebrova, V. V. Mikul'shina, P. V. Petrovsky, V. I. Robas, and 0. A. Reutov, J. Organometallic Chem., 1976, 110,49. W. Winter, Tetrahedron Letters, 1975, 3913. P. E. Ronman, Ph.D. Thesis, Florida State University, 1975 (Univ. Microfilms, Order No. 75-17948). A. N. Hughes, K. Amornraksa, S. Phisuthkul, and V. Reutrakul, J. Heterocyclic Chem., 1976, 13, 65. J. Luber and A. Schmidpeter, Angew Chem. Znrernat. Edn., 1976, 15, 11 1.

29

Phosphines and Phosphonium Salts

The co-ordination chemistry of heterocyclic phosphines, including various phospholes, has been reviewed.ls8 4 Phosphorins

The reaction of the stannane (176) with phosphorus trichloride gives the phosphorin (177). The electron-donating methyl group reinforces the ring dipole, the negative end of which is the phosphorus atom.16@ The dibenzo analogue (178) has also been prepared and its electronic structure studied by photoelectron spectroscopy.16o

The synthesis of the planar, tricyclic-P-phosphorin (179) has been described.lal It reacts with methyl iodide to give the salt (180) as a mixture of stereoisomers, and is in equilibrium with the ylide (181), which reacts with benzaldehyde to give the oxide (182).

a Ph’

‘CH,Ph

(179)

& Ph’

15* 159 160

H H \/

‘CHPh

D.G.Holah, A. N. Hughes, and K. Wright, Coordination Chern. Rev., 1975,15,239. A. J. Ashe and W.-T. Chan, Tetrahedron Letters, 1975, 2749. C. Jongsma, H.Vermeer, F. Bickelhaupt, W. Schafer, and A. Schweig, Tetrahedron, 1975,31, 2931. C. Jongsma, F. J. M. Freijee, and F. Bickelhaupt, Tetrahedron Letters, 1976, 481.

30

Organophosphorus Chemistry

Pyrolysis of the dihydrophosphorin (183) occurs with 1,dmigration of a phenyl grouplS2to give (184).

A number of reactions of monocyclic phosphorins have also been described. The A3-phosphorins(185) react with diazoalkanesin the presence of protic nucleophiles163 and with diazonium tetrafluoroborates in the presence of alcohols or phenolslp4to give the A5-phosphorins(186) and (187).

A5-Phosphorins having a phenyl residue at C-4 [e.g. (188)] are arylated in the aryl ring by aryldiazonium ~ a 1 t s .The l ~ ~ethoxycarbonyl group of the P-phosphorin (189) can be hydrolysed, transesterified, or reduced without destroying the ring system.lss

162 163 164 165

1G6

C. Jongsma, R. Lourens, and F. Bickelhaupt, Tetrahedron, 1976, 32, 121. P. Kieselack, C. Helland, and K. Dimroth, Chern. Ber., 1975, 108, 3656. 0. Schaffer and K. Dimroth, Cliem. Ber., 1975, 108, 3271. 0. Schaffer and K. Dimroth, Chern. Ber., 1975, 108, 3281. K. Dimroth and P. Kieselack, Chern. Ber., 1975, 108, 3671.

3

L

Quinquecovalent Phosphorus Compounds BY S. TRIPPETT

1 Introduction Perhaps the most surprising and potentially significant development in the year under review has been the preparation of stable, isolable, phosphoranes of the general formula (1). Examples include (2), formed from dineopentyl phosphonite and pinaco1,l and (3), formed by the addition of phenols to phosphorus(rI1) species.2p3

X = 0 or NH; R1= Me,Et, or Ph; R2= H, 0-NIi,, or 0-OH

Such phosphoranes are potential reducing agents; mild oxidation of (4), or rleat ng, gives the spirophosphorane (5) whereas (6) is slowly transformed into the spirophosphorane (7) at 0 0C.3 In general, cyclic PH-phosphoranes of structure (8) are in equilibrium in solution with the phosphorus(Ir1) species (9).3

Although the phosphoranes (1) so far detected are all stabilized by the presence of a ring, acyclic analoguespresumably exist in solution, and there are clearly interesting 1 2

W. Stec, B. Uznanski, D. Houalla, and R. Wolf, Compt. rend., 1975, 281, C , 727. S . A. Terent’eva, M. A. Pudovik, A. N. Pudovik, and Kh. E. Kharlampidi, J . Gen. Chem. (U.S.S.R.), 1975, 45, 2515. C. Malavaud and J. Barrans, Tetrahedron Letters, 1975, 3077.

31

Organophosphorus Chemistry

32

Me

developments ahead in the general area of the reactions of phosphorus(1n) compounds with alcohols, diols, and related compounds. 2 Structure and Bonding &Ray analysis has revealed trigonal-bipyramidal geometry in pentaphenoxyphosphorane4 and 'distorted' trigonal-bipyramidal geometry in the phosphoranes (10); (11),6(12),7(13),*(14),9and (15).1° The nitrogens in (12), (13), and (14) are planar and in (14) the mesityl ring is orthogonal to the other ring system. Structure (15)

R. Sarma, F. Ramirez, B. McKeever, J. F. Maracek, and S. Lee, J. Amer. Chem. SOC., 1976,98, 581. R. Sarma, F. Ramirez, and J. F. Maracek, J. Org. Chem., 1976, 41, 473. M. Fild, W. S . Sheldrick, and T. Stankiewicz, 2. anorg. Chem., 1975, 415, 43. W. S. Sheldrick, A. Schmidpeter, and J. H. Weinmaier, Angew. Chem. Znternat. Edn., 1975,14, 490. 9 10

J. I. G. Cadogan, R. 0. Gould, and N. J. Tweddle, J.C.S. Chem. Comm., 1975, 773. J. I. G. Cadogan, R. 0. Gould, S. E. B. Gould, P. A. Sadler, S. J. Swire, and B. S. Tait, J.C.S. Perkin I , 1975, 2392. H. A. E. Aly, J. H. Barlow, D. R. Russell, D. J. H. Smith, M. Swindles, and S. Trippett, J.C.S. Clzem. Comm., 1976, 449.

33

Quinquecovalent Phosphorus Compounds

shows how little distortion is required to accommodate a formally diequatorial fourmembered ring; the compound itself is remarkably stable. X-Ray analysis has shownll that the salt (16) is clearly trigonal bipyramidal round phosphorus. ~ J P for H (16) is 791 Hz and the P-N distance 1.986 A.

(16)

Electron diffraction has shown12that (CF3)zPC13is trigonal bipyramidal, with both trifluoromethyl groups apical and the fluorines staggeredwith respect to the equatorial chlorines whereas (CF,),PCl, has distorted trigonal-bipyramidalgeometry, with two apical trifluoromethyl groups. Ab initio SCF calculation^^^ on the series PHnFs-n and extended Huckel calculat i o n ~ on ~ * this series and on PMenF5-n have been reported. The latter trace the increasing apical PF bond length on successive replacement of equatorial fluorines by hydrogen or methyl to an increasing repulsive interaction between fluorine lonepairs and equatorial 0-bonds. Ab initio calculationsl5 on Berry pseudorotation and turnstile rotation in PH5gave free energies of activation of 1.95 and 10.05 kcal mol-1 respectively, and led to the conclusion that, in structurally flexible phosphoranes, turnstile rotation is a vibrationally excited mode of Berry pseudorotation. Calculationsla on phosphoranes of the general structure (17) show that square-pyramidal geometry is favoured by enhanced electronegativity in X and Y and by enhanced electropositivity in Z. Mixed hetero-ring atoms favour trigonal-bipyramidal geometry.

11 12 13 14 l5

J. C. Clardy, D. S. Milbrath, J. P. Springer, and J. G. Verkade, J. Amer. Chem. SOC.,1976,98, 623. H.Oberhammer and J. Grobe, 2.Naturforsch., 1975, 30b, 506. F. Keil and W. Kutzelnigg, J. Amer. Chem. SOC.,1975, 97, 3623. J. M. Howells, J. Amer. Chem. Soc., 1975, 97, 3930. J. A. Altmann, K. Yates, and I. G. Csizmadia, J . Amer. Chem. Soc., 1976, 98, 1450. R. R. Holmes, J. Amer. Chem. Soc., 1975, 97, 5379.

34

Organophosphorus Chemistry

3 Acyclic Systems The difluorophosphoranes(1 8),17 (19),18and (20) l8 have been obtained using xenon difluoride as shown. The most stable conformations of the trifluorophosphoranes (21) l9 and (22) 2o have apical fluorines; pseudorotation was slow on the n.m.r. timescale below - 60 "C(21) and - 40 "C (22). The intermolecular exchanges of fluorines

R,PH

f

XeF2 -+ K,PllF2

R = Ph or CII,CH,CN RPH2+XeFz

-*

R = CJ, or CII,CIIzCN KPC1,i HI?

R = Me, Et, Bu,But, or Ph

(19)

RPH2F2 (20)

RPIIF, (21)

in Me,PF, and in Me3PF2,previously monitored by n.m.r. in Pyrex tubes, have now been shown 21 to be due to impurities in the Pyrex. In Kel-F or Teflon tubes exchange is intramolecular. This, and the previous case of Ph2PF3,22 emphasizes that variabletemperature n.m.r. data on fluorophosphoranes must be treated with caution unless carried out in inert tubes. The trifluoromethylphosphoranes (CF,),PMe, and (CF,),PMe, have been obtained as stable, unreactive, white solids from the reactions of tetramethyl-lead with the corresponding chlorophosphoranes.23Pseudorotation of (CF,),PMe, is slow on the n.m.r. time-scale at 100 "C, indicating a very considerable difference in apicophilicity between methyl and trifluoromethyl groups. Among other acyclic phosphoranes prepared are (23),24(24),25and (25).26 Conductivity measurements on the phenoxyphosphoranes (26; M = 1,2, or 3) in 17

18 19 2o

22 23 24 25 26

S. Trippett and P. J. Whittle, J.C.S. Perkin I , 1975, 1220. J. A. Gibson, R. K. Marat, and A. F. Janzen, Canad. J . Chem., 1975, 53, 3044. R. Appel and A. Gilak, Chem. Ber., 1975, 108, 2693. E. R. Falardeau, K. W. Morse, and J. G. Morse, Inorg. Chem., 1975, 14, 1239. C. G. Moreland, G. 0. Doak, L. B. Littlefield, N. S. Walker, J. W. Gilje, R. W. Braun, and A. H. Cowley, J. Amer. Chem. SOC.,1976,98, 2161. C. G. Moreland, G. 0. Doak, and L. B. Littlefield, J. Amer. Chem. SOC.,1973, 95, 255. K. I. The and R. G . Cavell, J.C.S. Chem. Comm., 1975, 716. E. S. Kozlov, S. N. Gaidamaka, and L. I. Samarai, J. Gen. Chem. (U.S.S.R.), 1975, 45, 458. J. A. Gibson and R. Schmutzler, 2.anorg. Chem., 1975,416,222. U . Utebaev, E. M. Rokhlin, E. P. Lur'e, and I. L. Knunyants, Izoesr. Akad. Nauk S.S.S.R., Ser. khim., 1975, 1463.

Quinquecounlent Phosphorus Compounds (CCl,),ClY=NCOCl

120"('

35 (CCl,),CI,PNCO

+ CO

(23) (CI:,),C=NNLi

(hleO),P

+ F,C=

+ RPF, -+ RF,PN=C(CF,),

C(CF,)CO,Me

-

(24) (McO),PE: -CF= C(CF,:,)CO,Me

(25)

acetonitrile have allowed the calculation, on the basis of a number of necessary assumptions, of the equilibrium constants Kl and K227 [equations (1) and (2)]. For

PhP(OPh), Kl = (3 k 5 ) x 10-lo and K 2< 1 x moll-l. In general, the more oxygens attached to phosphorus the less the dissociation of the phenoxyphosphorane. The rate constants for the dissociation of a number of the phenoxyphosphoranes(26) were obtained from a study of thevariable-temperature n.m.r. of equimolar mixtures of the phosphoranes and the related phosphonium triflates Rnh(OPh)4-nCF3S03-.28 Together with the equilibrium constants Kl for these dissociations, these led to the conclusion that the reactions of the cations Rn$(OPh),-% with phenoxide ion in acetonitrile proceed with the speed of collision. 4 Four-membered Rings Details have appeared of the preparation and variable-temperature n.m.r. of the difluorophosphoranes (27), (29), and (30).29Only with (27) was the conformer (28), with a diequatorial four-membered ring, detected at low temperatures. Interconversion of the cis- and trans-isomers of (30) was slow on the n.m.r. time-scaleat - 90 "C.

* 1'

F

(27)

+

+IPPh

V-Ph

F

I; (28)

--fLp11 p\f:

1

F (2%

PF

P

F (30)

The variable-temperature l9Fand 31Pn.m.r. spectra of the diazadiphosphetidines (31)30 and (32)31have been recorded. Analysis32of the n.m.r. spectra of the phosphorane (33) indicates that the lone fluorine is basically equatorial rather than apical. 27 28

29 30 31 32

C. L. Lerman and F. H. Westheimer, J . Amer. Chern. SOC.,1976, 98, 179. D. I. Phillips, I. Szele, and F. H. Westheimer, J. Amer. Chem. Soc., 1976, 98, 184. N. J. De'ath, D. B. Denney, D. Z . Denney, and Y.F. Hsu, J . Amer. Cliem. SOC., 1976,98, 768. R. K. Harris, M. 1. M. Wazeer, 0. Schlak, and R. Schmutzler, J.C,S. Dalton, 1976, 17. R. K. Harris and M. I. M. Wazeer, J.C.S. Dalton, 1976, 302. R. K. Harris, M. I. M. Wazeer, 0.Schlak, and R. Schmutzlcr, J.C,S, Dalton, 1976, 306.

Organophosphorus Chemistry

36

Mc

(31)

ooLi

R = Me, Et, PI', or Rut

(F3PNMe), +

(3 2)

I:,P-NMe

--+

OLi

1

McN-P-,

I/F

19

5 Five-membered Rings Phospho1es.-Pyrolysis of the bisbiphenylylene-phosplioranes (34) gave the phosphines (35) when R was small, e.g. Me or Ph, but the phosphines (36) when R was

.~~ or ethanolysis of the spirophosphorlarge, e.g. 8-quinolyl or 9 - a n t h r ~ lHydrolysis ane (37), using water or ethanol labelled with laO,followed by acid hydrolysis, gave the labelled oxide (40) and the catechols (39).54Although rationalized in terms of stable, and isolated, hydroxyphosphoranes (38), in view of the 31P chemical shifts recorded for these it is probable that they are hydrogen-bonded complexes of (39) and (40). The migration of ethyl to catechyl-oxygen in the ethanolysis of (37) is noteworthy.

33 34

D. Hellwinkel and W. Lindner, Chem. Ber., 1976, 109, 1497. N. A. Razumova, N. A. Kurshakova, and A, A. Petrov, J. Gen. Chem. (U.S.S.R.), 1975,45, 686.

Quinquecovalent Phosphorus Compounds

37

1,2-Oxaphospholans.-The stable phosphoranes (41) were obtained from ylides and epi~hlorohydrin.3~ The formation of (41 ;R = H) from the action of base on the salt (42) supports a mechanism via the intermediate ylides (43). The crystalline cyclic

acyloxy- or amido-phosphoranes (45) were obtained in high yield from the cyclic phosphonite (44)and acrylic acid or acrylamide respectively under mild c ~ n d i t i o n s . ~ ~

+ CH,=CHCOXH (44)

--+

X=OorNH

0-p

Y

1,3,2-Dioxaphospholans.-l,2-Diols with TDAP and carbon tetrachloride gave either epoxides (46) or, more commonly, spirophosphoranes (47).37cis-Cyclohexane-

h ~CL, + CEICI, Wil

35

36 37

A. Turcant and M. Le Come, Tetrahedron Letters, 1976, 1277. T. Saegusa, S. Kubayashi, and Y . Kimura, J.C.S. Chem. Comm.,1976,443. R. Boigegrain and B. Castro, Tetrahedron Letters, 1975, 3459; Tetrahedron, 1976, 32, 1283.

38

Organophosphorus Chemistry

1,2-diol gives initially one symmetrical isomer, either (48) or (49), which rapidly equilibrates (AG*N" 24 kcal mol-l) with the other two possible isomers. Another account of the condensation of cyclic phosphites with benzoyl cyanide has appeared.38

Details have appeared 3 D of the addition of PH-tetraoxyspirophosphoranes to aldehydes and activated ketones. These phosphoranes also add to activated acetylacetylenedicarboxylatewith (50) gives a mixture of cis- and trunse n e ~e.g. , ~ diethyl ~ (51). Further addition of (50) to (51) at higher temperatures gives the bisphosphorane (52). Metallation of the spirophosphorane (53) followed by reaction with

alkyl halides41or benzoyl chloride17 gives the phosphoranes (54). The anion from (53) is probably an equilibrium mixture of (55) and (56); Me,SiCl gives the trimethylsilyl ether derived from (56). The pseudorotational behaviour of (54;R = PhCO) suggests that the benzoyl group is highly apicophilic.

38

3D 40 41

I. V. Konovalova, E. Kh. Ofitserova, N. P. Anoshina, and A. N. Pudovik, J . Gen. Chem (U.S.S.R.), 1975, 45, 2088. H. Germa and R. Burgada, Bull. SOC. chim. France, 1975, 2607. R. Burgada, Compt. rend., 1976, 282, C , 849. P. Savignac, B. Richard, Y.Leroux, and R. Burgada, J. Organoinetallic Chem., 1975,93, 331.

39

Quinquecovalent Phosphorus Compounds

Pseudorotation in the phosphoranes (57) and (58) has been studied using variabletemperature 13C n.m.r. spectroscopy.4aThe results on (57; R = Me) agree with those previously obtained using proton resonance.

hie

Me (57)

R = H or Me

R =HorMe

(58)

1,3,2-Dioxaphospholens-The condensationof a-diketoneswith tervalent phosphorus compounds has been extended to mon~thiobenzil.~~ Hydrolysis of the resulting adducts (59) gave both P-0 and P-S bond fission. Exchange reactions on the benzil-

PhCOCSPh + RP(OMe)?

'7-

O,/

R/=\ I OMe OMe

(59)

trimethyl phosphite adduct (60) have been carried out with amino-alcohols, ahydroxy-acids, and catechol (Scheme l).44The benzil-TDAP adduct (61) with norephedrine gave (62). This crystallized as one isomer, which equilibrated with the other at 60 "C in solution. The spirophosphorane (64)was obtained in high yield from catechol and phosphorous acid in the presence of DCC.45With [ h y d r o ~ y - ~ H ] catechol there was -=5 % incorporation of deuterium into (a), showing that in the intermediate (63) there was no tautomerism to the PII1species. The reaction of the biacetyl-trimethyl phosphite adduct (65) with acyl isocyanates has been extended to the isocyanates ROCO.NC0 and PhCS.NC0.46 With the thiazolin-4,5-diones (66), (65) gave the thiazol-4-ones (67). 42 43 44 45 46

G. Buono and J. R. Llinas, Tetrahedron Letters, 1976, 749. B. A. Arbuzov, N. A. Polezhaeva, V. V. Smirnov, and A. A. Musina, Bull. Acad. Sci. U.S.S.R., 1975,24, 1548. D. Bernard and R. Burgada, Phosphorus, 1975, 5, 285. M. Gallagher, A. Munoz, G. Gence, and M. Koenig, J.C.S. Chem. Comm., 1976, 321. F. Ramirez, C. D. Telefus, and V. A. V. Prasad, Tetrahedron, 1975, 31, 2007.

OrganophosphorusChemistry

40

Me 0

r-7

Me Me 0, O ,

MeCO+f

X, N , 4

+RCX-NCO

P

RCX = ROC0 ox PhCS

i- (MeO),PO

K

(65)

Me 0

OSvN+(65) H 0

M,CO+( -+

R (66)

R = Ph or PhCH,S

SvN R

+ CO i(MeO),PO

(67)

The phosphoranes, e.g. (69), which are intermediates in the Arbusov reactions of the cyclic phosphite (68) with chlorine, bromine, and benzenesulphenyl chloride have been detected at low temperatures by 31Pn.m.r. spectros~opy.~~ A similar technique revealed the intermediate (71) in the reaction of the thiophosphate (70) with~hlorine.~~ 47 48

A. Skowrohska, J. Mikolajczak, and J. Michalski, J.C.S. Chem. Comm., 1975, 791. A. Skowrohska, J. Mikolajczak, and J. Michalski, J.C.S Chem. Comm., 1975, 986.

Quinquecovalent Phosphorus Compounds

41

a 'P -t35 p.p.m.

(69)

t a

p

<

s

C1,IEtCI) -90°C

C\ { - O E t

OEt (70)

c1

"P + 25 p.p.m.

(71)

1,3,2-Oxazaphospholidines.-The phosphoranes (72) were obtained from phosphineimines and epoxides as shown.4QPyrolysis gave phosphine oxide and aziridines. The

/*\

PhOCH,CII-CH,

+

R

R Ph$

Ph 3P=NR R = Me or Et

PhOCH,CH-CH, CH,OPh

(72)

bicyclic PH-phosphoranes (73) exist as one dl- and two rneso-forms.60In the n.m.r. spectrum of (73; R1,R2 = Me) the P-methyl signals due to the two rneso-forms coalesce at 110 "C, but the mechanism for this is not clear. #R2

R'P(NMe,),

+ HN

130°C

(73)

The spirophosphorane (74) has been identified as an intermediate in the formation of (75) from o-aminophenol and trisdiethylaminophosphine.61With ethylene glycol (75) gave high yields of the phosphoranes (76) and (77). As expected, the phosphoranes (78) have apical fluorine atoms.62The interesting bicyclic phosphoranes (79) and (80) have been prepared as R. Appel and M. Halstenberg, Chem. Ber., 1976, 109, 814. D. Houalla, J. Mouheich, M. Sanchez, and R. Wolf, Phosphorus, 1975, 5, 229. 61 M. A. Pudovik, S. A. Terent'eva, Y .Y . Samitov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.),

*9

6o

1975,45,252. 52

53

H. B. Stegmann, H. V. Dumm, and K. B. Ulmschneider, Tetrahedron Letters, 1976, 2007. A. Schmidpeter and J. H. Weinmaier, Angew. Chem. Internat. Edn., 1975, 14, 489.

42

Organophosphorus Chemistry

HO

1I

(76)

(77)

Details have appeared 64 of the formation, via spirodienyl intermediates, of phosphoranes containing a 1,3,2-0xazaphospholidine ring, e.g. (81), from the deoxygenation of aryl 2-nitrophenyl ethers with tervalent phosphorus compounds. The spirophosphorane (82) was obtained both by an exchange reaction between (81) and ethylene glycol and directly, using ethylene phenylphosphonite as deoxygenating agent. The spirophosphorane (86), produced in the reaction of the ether (83) with diethyl methylphosphonite, was formed from the expected product (84) via an exchange reaction with its hydrolysis product (85). The variable-temperature lH 54

J. I. G. Cadogan, D. S. B. Grace, P. K. K. Limy and B. S. Tait, J.C.S. Perkin I , 1975, 2376

43

(83)

.c.

Ar = p-MeOC,H,

-a:+p Ar

n.m.r. spectra of (8l), (82), and related phosphoranes have been described.66They are complicated by hindered rotation round the N-Ar bond. The deoxygenation of aryl 2-nitrophenyl sulphides with tervalent phosphorus compounds is analogous to that of the corresponding ethers except that in many cases the anticipated. phosphoranes, e.g. (87), are thermally unstable.66The extra stability of spirophosphoranes allows them to be isolated, e.g. (13), if cyclic phosphonites are used in deoxygenation.8 Photolysis of the phosphoranes (88) gave moderate yields of the carbazoles (89).57 55 66

57

J. I. G. Cadogan, D. S. B. Grace, and B. S. Tait, J.C.S. Perkin I , 1975, 2386. J. I. G. Cadogan and B. S. Tait, J.C.S. Perkin I, 1975, 2396 J. I. G. Cadogan, B. S. Tait, and N. J. Tweddle, J.C.S. Chem. Comm., 1975, 847.

44

Organophosphorus Chemistry r.

P(OEt),

A

+

xoz I

O

II

O

NP(OEt),

I

"O2

Y

Y

Miscellaneous.-The formation of the phosphonate (93) from the action of P,Slo on the phosphorane (go),"* and from trimethyl phosphite and the thioketone (91),59 probably involves the intermediate 1 ,2-thiaphosphole (92) in both cases. The forma-

hIe

C0,Et MeS

5.9

59

CHMe.P(OMe),

B. A. Arbuzov, N. A. Polezhaeva, and V. V. Smirnov, Bull. Acad. Sci. U.S.S.R., 1975,24,611. B. A. Arbuzov, N. A. Polezhaeva, and V. V. Smirnov, Bull. Acad. Sci. U.S.S.R., 1975,24,613.

45

Quinquecovalent Phosphorus Compounds

tion of the 1,3,5-oxazaphospholidines(93,in some cases in high yield, from the reactions of sulphonamides with formaldehyde and trialkyl phosphites may involve trapping by formaldehyde of the betaines (94).60 R1S02NH2+ H,CO --+R1S0,NHCH20H

__f

R'SO,N=CH,

(95)

In concentrated solution, trimethyl phosphite and the nitro-olefin (96) gave the phosphorane (97), whereas in dilute solution the phosphonate (98) was produced.61 Compound (97) was stable in refluxing ether but was converted into (98) in the

0

II

(MeO),PCMe(OMe)CMe(:NOH) (9 8)

presence of trimethyl phosphite. The nitrile ylides formed on thermal decomposition of the 1,3,5-oxazaphospholines (99) have now been trapped with vinyl ethers and, when R1 = But, with the ynamine The proton n.m.r. spectra of a series of phosphoranes (99) have been r e p ~ r t e d . ~ ~

(99)

OPh

Me

'NEt,

D. J. Scharf, J. Ore. Chem., 1976, 41, 28. R. D. Gareev, E. E. Borisova, and I. M. Shermergorn,J . Gen. Chem. (U.S.S.R.), 1975,45,929 e2 K. Burger, W.-D. Roth, K. Einhellig, and L. Hatzelmann, Chem. Ber., 1975, 108, 2737. 63 J. Albanbauer, K. Burger, E. Burgis, D. Marquarding, L. Schabl, and I. Ugi, Annalen, 1976,36.

60

61

46

Orgaiiophosphorw Chemistry

6 Six-membered Rings The 1,3,2-dioxaphosphorinans(101; R = C1, NMe,, or OMe), derived from trans2-hydroxymethy1cyc1opentano1, condensed with perfluorobiacetyl to give the expected phosph~ranes.~~ That from (101;R = OMe) probably had the relationship of methoxy to ring junction shown in (102);it slowly isomerized in solution at 40 "C to a 60:40 mixture with the isomer (103). The corresponding isomerizations

were rapid in the case of the chloro- and dimethylamino-analogues. The formation of the phosphorane from (101;R = OMe) and diethyl peroxides was less rapid than in the case of triethyl phosphite. (101; R = OMe) also condensed with o-chloroanil to give a phosphorane, which showed isomerism analogous to that of (102;R = OMe). The 1,3,2-0xazaphosphorines(105)were obtained from triaryl phosphites and the 3-cyano-3-halogenosuccinimides (104).66Because of their negative slP chemical

R' CN

R'

X

shifts, which vary with the solvent, the corresponding adducts (106) from phosphonites and phosphinites are probably in equilibrium in solution with the betaines (107).

7 Six-co-ordinate Species The major absorption in the 31Pn.m.r. spectrum of an equimolar solution of pentaphenoxyphosphorane and sodium phenoxide in DMF-acetonitrile is due to the hexaphenoxyphosphate anion, as predicted from the low equilibrium constant estimated for equation (2) (page 35).27Catechol and phosphorus oxychloride in refluxing benzene gave the spirophosphorane(108),which with triethylamine gave the salt (109).46On the basis of its 31Pchemical shift in DMF solution, (108)was formulatedss as the free six-co-ordinate acid (110), but it seems probable that DMF is 65

F. Ramirez, J. F. Marecek, I. Ugi, P. Lemmen, and D. Marquarding, Phosphorus, 1975, 5, 73. M. F. Pommeret-Chasle, A. Foucaud, M.Leduc, and M. Hassairi, Tetrahedron, 1975,31,2775.

66

J. Gloede and H. Gross, Tetrahedron Letters, 1976, 917.

64

Quinquecovalent Phosphorus Compoiinds

47

(108)

sufficiently basic to give a salt corresponding to (109) in solution. The extraordinarily stable salt (109) hasalsobeen prepared 6 6 in a variety of ways, some of which are shown in Scheme 2.

X = C1, NMe,, or OMe r

1

X = C1 or Ph

S=OorS Y = C1, OEt, or OPli

Scheme 2

48

Organophosphorus Chemistry

The phosphonamidite (1 11) and catechol, in the presence of base, gave initially the salt (112) and o-arninophen~l.~~ If the reaction mixture was allowed to stand at room temperature for a few days the final product was the spirophosphorane (113).

Further six-co-ordinate anions incorporating an a-hydroxy-acid residue, e.g. (114), have been prepared, and the use of salicylic acid has given the anion (1 15), containing

a six-membered ring.68The benzil-TDAP adduct (61) and catechol gave the salt (116).44

67

68

M. A. Pudovik, S. A. Terent'eva, and A. N. Pudovik, J . Gen. Chem. ([J.S.S.R.)1975,45,2292. A. Munoz, G. Gence, M. Koenig, and R. Wolf, Bull. SOC.chint. France, 1975, 1433.

Quinquecovalent Phosphorus Compounds

49

Oxidation of the spirophosphorane (64) in DMF with DMSO gave the phosphonate (63) and the saIt (117).sDThe reaction is thought to involve the hydroxy-

phosphorane (119) as shown, and to provide evidence for an equilibrium between the phosphate (118) and (119) (Scheme 3).

The trifluorophosphorane (120) with caesium fluoride gave the salt (121) and with trimethylphosphine gave the six-co-ordinate species (122), whose configuration was shown by 19Fn.m.r. spectros~opy.~~

69 70

A, Munoz, M. Gallagher, A, Klaebe, and R. Wolf, Tetrahedron Letters, 1976, 673. J. A. Gibson, G.-V. Roschenthaler, and R. Schmutzler, J.C.S. Dullon, 1975, 918.

3 Halogenophosphines and Related Compounds BY J. A. MILLER

1 Halogenophosphines The chemistry of the PIII-halogen bond continues to attract a good deal of attention. Unfortunately, much of the effort is undistinguished, and the best work has often been concerned with tidying up old reactions, rather than with breaking new ground. Physical and Structural Aspects.-Perhaps the most significant theoretical paper comes from an application of pseudopotential SCF methods to PX3 molecules.1 This method neglects core orbitals, and hence shortens computer-time requirements, in comparison with more conventional SCF calculations. The results1are really most encouraging, and compare favourably with standard SCF results, in relation to experimental values for bond angles and lengths, and for dipole moments. Photoelectron spectra have been obtained by three different groups working with halogenophosphine~,~-*and binding energies discussed in terms of electronic structure. Thus, for the trifluoromethyl derivatives(I), the ionization potential for the lone pair on phosphorus decreases steadily as n changes from n = 3 through to n = 0,2 in keeping with the high electronegativity for the trifluoromethyl group. The relatively high binding energy of the lone pair in phosphine is possibly related to its high s-character, as indicated by the small HPH bond angle. Other work in this field has been directed at simple phosphorus trihalides and their oxides and sulp h i d e ~while , ~ various methylphosphine derivatives have also been ~ t u d i e d . ~

Me

XlC

(4)

(3)

4

C. S. Ewig, P. Coffey, and J. R. van Wazer, Znorg. C h ~ m .1975, , 14, 1848. A. H. Cowley, M. J. S. Dewar, and D . W. Goodman, J . Atner. Chew. Sor., 1975, 97, 3653. R. G.Cavell, Znorg. Chem., 1975, 14,2828. S . Elbel and H. Dieck, Z . Naturforsch., 1976, 31b, 178.

50

Halogenophosphines and Re lafed Compoiirids

51

Miscellaneous spectral studies include e.s.r. spectra of chloro-phosphines(2) and vibrational spectra of various phosphines.6-8N.m.r. studies include those of borane complexes of aryldichloropho~phines,~ and studies of the conformation of dichloro(isopropy1)phosphine (3) lo and dichloro(ethy1)phosphine (4).1° These phosphines have the preferred conformations shown. Conformation has also been the theme of electron-diffraction work on the anhydride (3,which appears to have a staggered conformation.ll The electronic implications of a relatively short P - 0 bond and wide POP angle have been discussed.ll The basicity of halogenophosphines has attracted some attention this year. A careful study of the protonation of several halogenophosphines (6) has led to the characterization by 31Pn.m.r. of phosphonium species, such as (7).'* These salts show *lP shifts to relatively high fields, and large ~ J P H values; e.g., (7) has 1190Hz.l2 Attempts have been made to correlate phosphine basicity with ~ J Pvalues B in borane complexe~,~~ and, in turn, to correlate ~JPB with electrostatic interactions in the phosphorus-boron bond.13 From such correlations, the authors deduce that this bond is dominated by electrostatic contributions, and not by other factors, such as n-bonding. Preparation.-Two new synthetic routes to simple iodo-phosphines have appeared this year. Thus phosphorus tri-iodide (8) is produced in fairly good yield when the iodides of lanthanum, strontium, or europium are treated with the corresponding ~h0sphates.l~ Tetraiododiphosphine (9) is formed in 75-80 % yield, by the reaction

of phosphorus trichloride with potassium iodide,16 initially as a suspension in ether. This route appears to offer distinct advantages over those based on elemental phosphorus. The tetraiodide (10) is prepared as shown.ls When diphosphines are heated with carbon tetrachloride at 120-140 "C, chlorophosphines are formed, together with trichloromethyldialkylphosphines (1 1).17 B. W. Fullam and M. C. R. Symons, J.C.S. Dalton, 1975,861. A. I. Fishman, A. B. Remisov, I. Y. Kuramshin, and I. S. Pominov, Spectrochim. Actu, 1976, 32A,651. J. R. Durig and J. E. Saunders, J. Mol. Structure, 1975,27,403. * S. Reichman and J. Schatz, J, Mol. Spectroscopy, 1976,59,502. 9 E. Muylle and G. P. Van-der-Kelen, Spectrochim. Acta, 1976,32A, 599. 10 J. P. Dutasta and J. B. Robert, J.C.S. Chem. Comm., 1975,747. 11 H.Y. Yow, R. W. Rudolf, and L. S. Bartell, J. Mol. Structure, 1975,28,205. l2 L. J. Van de Griend and J. G. Verkade, J . Amer. Chem. SOC.,1975,97,5958. l3 L. F. Centofanti, J. Inorg. Nuclear Chem., 1976,38,265. l4 J. M. Haschke, Inorg. Chem., 1976,15,508. 15 G. R. Newkome, J. D. Sauer, and M. L. Erbland, J.C.S. Chem. Comm., 1975, 885. 1 6 Zh. K. Gorbatenko, I. T. Rozhdestvenskaya, and N. G. Feshchenko, J. Gen. Chem. (U.S.S.R.), 5

l7

1975,45,2325. R. Appel and R. Milker, Chem. Ber., 1975,108,1783.

52

Organophosphorus Chemisfry

3-Chloropropyldichlorophosphine(12) has been prepared as shown in Scheme 1 ,18 and several standard reactions have been carried out on (12).

CICH,CH,CI-I,Br

i-iv

+

C1CH,CH2C€I,PC12 (12)

0

It

Reagents: i, (Et0)PH

+

base; ii, PCk; iii, PZs5; iv, (Ph0)aP.

Scheme 1

Iodo(trBuoromethy1)phosphine (13) has been prepared l9 and found to undergo ligand exchangeas shown. Various reactions of (13) involving loss of iodine have also been describedin the same paper.lSOther workers have drawn attention to the general instability of chloro-phosphines of general structure (14), and found that one such example (14; R = Ph) may be stabilized by complexing to manganese, as in (15).20 Allyldibromophosphine (16) has been synthesized by the unusual route shown.21 2H,PCF,

+ I,

2HP(I)CF3

* H2PCF3

f

I,PCF3

(13) RP(H)Cl

(14) CH2=CIICHzPF'2

C&(CO)2Mn-P(15) HBr

/ph C1 '11

+ CH,=CHCH,PBr,

(16)

Reactions with Simple Alkenes and Aromatic Compounds,-A wide range of conditions continues to be used to form phosphorus-carbon bonds between halogenophosphines and alkenes or benzene derivatives. A selection of such reactions (Scheme 2) is outlined for the preparation of the compounds (17)-(23).22-26 The paper devoted to the phosphetan synthesis26describes optimum conditions for the cyclization process leading to (22), and explains the effects of other conditions in terms of competing reactions, such as alkene polymerization or addition of hydrogen chloride. Assignment of structure (23) to the product from hept-1-ene (24) 1* l9 Zo

21

23 24

25 26

S. G. Fattakhov and V. S . Reznik, Bull. Acad. Sci., U.S.S.R.,1975, 1311. R. C. Dobbie, P. D. Gosling, and B. P. Straughan, J.C.S. Dalton, 1975, 2368. G. Huttner and H.-D. Muller, Angew. Chem. Internat. Edn., 1975, 14, 571. E. R. Falardeau, K. W. Morse, and J. G. Morse, Inorg. Chem., 1975,14, 1239. R. I. Pyrkin, M. M.Gilyazov, and Ya. A. Levin, J. Gen. Chem. (U.S.S.R.),1975, 45, 750. P. A. Zagorets, A. G. Shostenko, and A. M. Dodonov, J. Gen. Chem. (U.S.S.R.),1975, 45, 2322. K. G. Weinberg, J. Org. Chem., 1975, 40,3586. J. Emsley, T. B. Middleton, and J. K. Williams, J.C.S. Dalton, 1976, 979. S. V. Fridland and M. V. Pobedimskaya, J. Gen. Chem. (U.S.S.R.),1975, 45, 227.

53

Halogenophosphines and Related Compormds (ref. 22)

i-i"

PhPCI, + CH,=CH,

*

PhP(C1) CH,CH,Cl

(17) 60% (ref. 23)

-% Cl,PCH,CH(CI)Me + CI,PCH(Me)CH,CI

PC1, + MeCH-CH,

(18) (ref. 24)

O

C

R

l + P

(19)

6 ArPCI, + Ar,PCl (21)

(20)

(white)

(22) (ref. 26) hept-l-ene + PBr,

A Br,PCH,CH(Br) (CH,),Me (23)

(24)

Reagents: i, AICb; ii, HzO; iii, PCb; iv, w a y s from cobalt-60; v, 280-350 vi, AlCb ( > 1 mol); vii, 0 2 , 65 "C.

"C, AlC13;

Scheme 2

continues a mild controversy as to whether oxidation at phosphorus occurs under such conditions. For example, other workers have isolated a phosphonic derivative (25) from a similar reaction.27

Reactions in which Phosphorus is E1ectrophilic.-Further study has been made of the reactions between chlorodialkylphosphines(26) and phosphites or phosphonites.28 By appropriate choice of the alkyl groups in (26), redistribution reactions can be inhibited and good yields of products (27) with P-P bonds are obtained.28 Displacement reactions at PII1have been carried out with the thallium salt of cyclopentadiene, and various phosphinocyclopentadienes(28) Triphenyl-

RiPCl

+ (MeO),PR2

(26) R' = But or C,H,,

-

0

II I R2

MeOPPRi

(27) R2 = Me orOMe 27

28

29

Y.Okamoto and H. Sakurai, Chem. Letters, 1973, 599. K. M. Abraham and J. R. van Wazer, Phosphorus, 1975,6,23. F. Mathey and J.-P. Lampin, Tetrahedron, 1975, 31, 2685.

3

54

Organophosphorus Chemistry

phosphazene (29) reacts with chlorodiphenylphosphe as S ~ O W I I .A ~ ~study of the reaction between phosphorus trichloride and ethanol has been reported?l

-

(28) R = Me or Ph

Ph,P=NH

+ PhzPC1

(29)

Ph,P=NPPh,

Biphilic Reactions.-A most thorough investigation into the cycloaddition of buta1,3-diene with dichloro(methy1)phosphine (30) has revealed some of the factors which influence the composition of the final Thus the A3-phospholen 1-oxide(31) is the product of the cycloaddition at room temperature, but at 90 "Cthe isomeric A2-phospholen1-oxide (32) predominates after work-up. The yields of (31) and (32) are improved by a new work-up involving methanolysis rather than hydrolysis of the intermediate

MePQ (30)

+

CH,=CHCH=CH,

*OoC

0

+ c1M k 'Cl

MeOH

~

0 /

Me

Treatment of phosphorus trichloride with isoprene in the presence of acetone leads to 1-chlorophospholen 1-oxides (33).aaEvidence has been presented that the diene reacts first with the trichloride to produce (34), which then reacts with acetone.331-Bromo-3,4-dimethyl-A3-phospholen (35) does not form a spiro-compound with 2,3-dimethylbuta-l,3-diene,although the bisphospholen derivative (36) has been isolated after hydrolytic w~rk-up.~* Diphenylphosphinoisocyanate(37) undergoes a 1,3-dipolar addition to dimethyl acetylenedicarboxylate,but the adduct (38) could not be isolated in a pure state, and was further hydrolysed to (39).3s 30 31 32 33 94 35

M. Biddlestone and R. A. Shaw, J.C.S. Dalton, 1975,2527. T. Kh. Gazizov, V. A. Karlamov, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1975,45,2295. K. Moedritzer, Synth. React. Inorg. Metal-Org. Chem., 1975,5, 299. B. A. Arbusov, A. 0. Vizel, R. S. Giniyatullin, L. I. Shchukina, and N. P. Anoshina, J. Gen. Chem. (U.S.S.R.), 1975, 45, 507. F. Mathey and D. Thavard, Compt. rend., 1975,281, C, 243. L. S. Rodionova, V. A. Galishev, V. N. Chistokletov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1623.

Halogenophosphines and Related Compounds

55

PCI, +

v Br

(33)

(34)

+

Ph,PNCO (37)

+

MeO,CC-CCO,Me

-

0

0

Ph,P

9@ H20 s

I1 Ph,PC(CO,Me)=C

'CONH,

C0,Me

MeO,C

,CO,Me

(39)

(38)

The phosphine oxide (40) has been confirmed as the product of the reaction of chlorodiphenylphosphine with trifluoroacetic Reasonable speculation has been made about the pathway to (40), although the question of direct addition to the carbonyl oxygen of the ketophosphine oxide (41) remains unanswered,s6as indicated in Scheme 3. Ph,PCl + CF,CO,H

Ph,POCOCF, + HCl

=G==

+==

CF,COCl

+ Ph, H

Ti

0

0

II

Ph,PCOCF3

&?

(41)

\t 0

It

d h l C ( O H ) CF3

Ph,PCH(CF,) OPPh,

rearrangement?

Reagent: i, PhaPHO.

(4Q)

Scheme 3

Chlorodi-t-butylphosphine(42) reacts with benzoates as shown, and evidence has been presented for the initial nucleophilic r81e of (42), with phosphorus attacking at 36

P. Sartori, R. H. Hochleitner, and G . Haegele, 2.Naturforsch., 1976, 31b, 76.

OrganophosphorusChemistry

56

both the alkyl and carbonyl groups of the benzoate.37The formation of t-butyl(dibenzy1)phosphine oxide (43) is believed to result from loss of isobutylene from a phosphonium intermediate, as shown in Scheme 4.

J. 0

CH,Ph

But,P+'

-0COAr

a' 'CNzPh

'f

HOCOAs

ester:

-t.

Bu',PCH,Ph + ArCOCl

I i i Ri?P(CH,Ph),

(43)

The products that were isolated are boxed.

Scheme 4

A study of the reactions of halogeno-phosphines with ketone derivatives has been extended to (44), which forms a heterocycle (45a) with dichloro(pheny1)phosphine 38 under neutral conditions. The analogous oxide (45b) has already been isolated from

SH

I

Me,CCH,COMe (44)

+ PhPC1, --+

xAP11 (45) a;

X = S

b;X = 0 0

RCHO + PCI,

2o OC :

(RCEICI),O (46)

37

'20

"' : RCHCI,

.

'5I'

II

OC

+ P-CHCIPCI,

(47)

N . J. De'ath, S. T. McNeilly, and J. A. Miller, J.C.S. Perkin I , 1976, 741. N. I. Rizpolozhenskii, L. V. Stepashkina, and R. M. Eliseenkova, Bull. Acad. Sci., U.S.S.R., 1974,2039.

57

Halogenophosphines and Related Compounds

the reactions of diacetone Details have appeared of the reactions of phosphorus trichloride with aldehydes, which yield bis(a-chloro-alkyl) ethers (46), gemdichlorides, or a-chloro-alkylphosphonicdichlorides (47), depending upon experimental conditions and the structure of the aldehyde.40 A very elegant analysis has been presented41 of the factors which control the complex reactions known to occur between chloro-phosphines and acetals. In particular, 31Pn.m.r. and thermographic analysis of the reactions of acetaldehyde diethylacetal(48) with a wide range of chloro-phosphines has revealed the stepwise nature of the replacement of the halogens.41Kinetic studies41indicate the following orders of reactivity for the halogeno-phosphines, and imply a change in the r81e of phosphorus when substituted by two ethyl groups : PC13 > PhPClz > PhzPCl PCls > EtPClz < EtzPCl

In Scheme 5 the suggested pathway is shown for the conversion of phosphorus trichloride and (48) into the main product, the phosphonate (49). PCl,

+ MeCH(OEt), =+= EtOPCl, + MeCH(C1)OEt (48)

(EtO),PCl

f

MeCH(C1)OEt

0

II

(EtO),PCH(OE t) Me

t

(E tO),P + MeCH(C1) OEt

(49) Reagent: i, (48).

Scheme 5

The iodo-phosphine (50) decomposes at temperatures above -50 "C to give the phosphorane (51).42 Phosphorus trichloride is oxidized by the sulphenyl chloride (52).45 Aryl- and alkyl-dichlorophosphineshave been converted into the phosphor3PhOP1, (50)

-

(PhO),PI, (51) 54%

PCl,

79% S

0

II + CISP(OR),

+ P,J,

pocl,

I1

+ ClP(OR),

(52) 39 40

41 42

43

B. A. Arbusov, N. I. Rizpolozhenskii, A. 0. Vizel, K. I. Ivanovskaya, F. S. Mukhametov, and E. I. Gol'dfarb, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1971, 117. J. A. Miller and M. J. Nunn, J.C.S. Perkin I, 1976, 535. M. B. Gazizov, D. B. Sultanova, A. I. Razumov, T. V. Zykova, N. A. Anoshina, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1670. N. G . Feshchenko and V. G. Kostina, J . Gen. Chem. (U.S.S.R.), 1975,45, 269. N. I. Gusar and M. P. Chaus, J. Gen. Chem. (U.S.S.R.), 1975, 45, 2384.

Organophosphorus Chemistry

58 RPCI, -% RPF,H

R = alkyl or aryl

(53)

anes (53) by an unusual exchange-addition pathway.44Several difluorophosphoranes (54) have been prepared by the reaction of difluorophosphines with hexafluoroacetone.46Details of these reactions appear in Section 2 of this chapter. Tetraiododiphosphine(9) has been used to remove hydroxy-groups from 1,4diols, Yields of 75 % have been obtained as shown in the preparations of (55)15 and in the conversion of chloro-phosphinesinto phosphinates (57), by treatment with an alcohol-base mixture in carbon tetra~hloride.~' OH

OH I

Ph-b.-C=C-&--Ph

I

I

I

PY

(9)

pyridine

*

PY

Ph(py)C-C=C=C(py)Ph (55)

OH

/R

OH 0

RiPC1 + R'OH

-I-CCl,

base

II

+ R:POR2 + HCC1, + R2c1 + HQ

Miscellaneous Reactions.-The reaction of phosphorus trichloride with toluene in the presence of oxygen is known to yield the hydrocarbon (58) and benzylphosphonic dichloride (59).48 The product ratio is now found to be greatly dependent upon the partial pressure of oxygen,"O and earlier views on the relation between the products have been altered. 44 46 46

*7 48 49

R. Appel and A. Gilak, Chem. Ber., 1975, 108, 2693. J . A. Gibson, G.-V.Roschenthaler, and R. Schmutzler, J.C.S. Dalton, 1975, 918. T. Manafusa, S. Imai, K. Ghkata, H. Suzuki, and Y . Suzuki, J.C.S. Chem. Comrn., 1974, 73. R. Appel and U. Warnung, Chem. Ber., 1976,109,805. T . Okada, Y.Okamoto, and H. Sakurai, Bull. Chem. Soc. Japan, 1974,47,2251. Y . Okamoto and H. Sakurai, Bull. Chem. SOC.Japan, 1975, 48, 3407.

Halogenophosphines and Related Compounds

59

0 -

ii

PhMe + PCl, + 0, + PhCH,PC1,

+

PhCH,Ph(Me)

(59)

(5 8)

(60)

A range of reactions of 2-chlorocyclohexyl(dichloro)phosphine (60)with alcohols and epoxides has been described, largely with a view to the synthesis of polymer intermediates and flame-retardant~.~~ The copolymerization of dichloro(pheny1)phosphine with styrene and vinyl butyl ether in the presence of maleic anhydride has been st~died.~' Silyl- and Related Phosphines.-A new preparation of tris(trimethylsily1)phosphine (61) from white phosphorus has been reported.sa Lithium derivatives of (61) may be prepared by cleavage with butyl-lithi~rn,~~ using glyme as solvent. P(white) + Me,SiCl

(Me,Si),P

Na-K

i;g

:CMe,Si),PLi

(61)

A number of exchange reactions of di-t-butyl(trimethylsily1)phosphine (62) have been described.sp-5 They generally involve cleavage of the silicon-phosphorus bond of (62), and a selection is outlined in Scheme 6. Buf,PCl

Me,Sn(PBu',),

+ Me,SiCf

Buf2PSiMe,

Buf,PMCI3 t. Me,SiCI

(62)

But,PGe(C1) Me,

Me,Sn (PBd, ),

Reagents: i, SnC14 (ref. 54); ii, GeCh or SIC14 (ref. 54); iii, MeeSnCl2 (ref. 55); iv, MezGeCh (ref. 56); v, MezSn(C1)PBu'n (ref. 57). Scheme 6 50 51

62 68

54 55 56

57

Ya. A. Levin, M. M. Gilyazov, and E. I. Babkina, J. Gen. Chem. (U.S.S.R.),1975,44,2586. N. D. Kazakova, L. B. Triskina, and S . R. Fafikov, Izuest. Akud. Nuuk Kuzukh. S.S.R., Ser. khim., 1975,25,56. G. Becker and W. Holderich, Chem. Ber., 1975,108,2484. G. Fritz and W. Holderich, 2.anorg. Chem., 1976,422,104. W.-W. Du Mont and H. Schumann, Angew. Chem. Znternat. Edn., 1975,14,368. H.Schumann and W.-W. Du Mont, 2.Nuturforsch., 1976,31b,90. H.Schumann and W.-W. Du Mont, Chem. Ber., 1975,108,2261. H.Schumann, W.-W. Du Mont, and B. Wobke, Chem. Ber., 1976,109, 1017.

Organophosphorus Chemistry

60

Dimethyl(trimethylsilyl)phosphine (63) reacts with aluminium chlorides with cleavage of the silicon-phosphorus bond,68as shown for aluminium trichloride. The same phosphine (63) reacts with the cobalt derivative (64)as shown.6s AICI,

+ Me,SiPMe,

--+

adduct -% (ChAlPMe,),

(63)

I".";;;(coh

(MqSi),$Me,

co(CO),

Diacylphosphines may be prepared by treatment of bis(trimethylsilyl)phenylphosphine (65) with acid chlorides.6oA diphosphine derivative (66) is formed with benzoyl chloride.6O A series of complex reactions occurs between nitrobenzenes and diphenyl(trimethylsily1)phosphine (67).61 The oxides noted below were the only isolable products, and the yields were not high.ll

I

PkP(SiMe,), + 2RCOCl

(PhCOPPh),

(66)

--w

PhP(COR),

+ 2Me,SiCI

(65)

R = H 01 4-Cl

R = 2-(3

Carbonyl-addition reactions continue to be the speciality of the French group interested in germylphosphines. Thus the germaphospholan (68) adds to aldehydes to give diastereomeric products (69).62Steric factors are believed to control the mode

3

Me,Ge Ph

+ RCHO

* O-CHR

of 1,4-addition of various Group IV phosphines to orp-unsaturated carbonyl compounds, while hard-soft interactions are suggested to determine the balance between 1,2- and 1,4-additi0n.~~ 59 6o

61 62

63

G. Fritz and R. Emul, 2. anorg. Chem., 1975,416, 19. H. Schafer and A. G. MacDiarmid, Znorg. Chem., 1976,15, 848. D. Fenske, E. Langer, M. Heymann, and H. J. Becher, Chem. Ber., 1976,109, 359. D. Fenske, H. Teichert, and H. J. Becher, Chem. Ber., 1976, 109, 363. C. Couret, J. Escudie, J. Satge, and G . Redoules, J. Organometallic Chem., 1975,94, C35. C. Couret, J. Escudie, J. Satge, N. T. Anh, and G . Soussan, J. Organometallic Chem., 1975,91, 11.

Halogenophosphinesand Related Compounds

61

Addition reactions of silylphosphinesto imines have been reportedYs4 as illustrated for diethyl(trimethylsily1)phosphine (70). Organic azides react with germylphosphines by an insertion pathwayYB5 as shown for various phenyl(trimethy1germyl)phosphines (71). The initial products (72) isomerize to phosphine imines on heating.65

\

M%SiPEt, + C=NR (70) / Me,GeP(R‘)Me

(71)

+ RaN,

-

1

Me,SiN(R)CPEt,

I

Me,GeN(Ra)P(R’)Me

6 Me,GeP(R’) Me

ll

(72)

NR’

2 Halogenophosphoranes Physical and Structural Aspects.-Fluorophosphoranes (73) feature prominently in an extensive ab initio SCF study of the bonding in fluoro-derivatives of Group V elements.66Using different basis sets, the authors have demonstrated, yet again, the energetic benefits of including d-orbitals.66A somewhat different application of MO methods has been reported by Howell,67 who has used extended Huckel and CNDO/2 calculations to probe the structural changes in phosphorus pentafluoride (73; n = 0) as the fluorine nuclei are replaced by hydrogen or by methyl groups. In particular, the relatively greater stretching of axial P-F bonds (relative to equatorial P-F) experimentally observed for a number of substituted fluorophosphoranes has been ascribed to a repulsive interaction between the equatorial a-bonds and the axial lone pair of fluorine.67 The question of the energetics of trigonal-bipyramidal (TBP) as against squarepyramidal (SP)structures has been analysed for phosphoranes in which phosphorus is incorporated into a five-membered (or smaller) ring.68Holmes has discussed the importance of the difference between axial and equatorial bond lengths to phosphorus, in a TBP structure, and shown that this induces significant ( 3 - 4 kcal mol-l) strain when the phosphorane possesses an unsaturated five-membered ring bonded by electronegative elements to the phosphorus.68This effect is likely to be enhanced

(74) R = F (75) R = Me 6* 65 66 67 68

Br (76)

C. Couret, F. Couret, J. Satge, and J. Escudie, Helu. Chim. Acta, 1975, 58, 1316. J. Escudie, C. Couret, and J. Satge, Compt. rend., 1975, 280, C, 783. F. Keil and W. Kutzelnigg, J. Amer. Chem. SOC.,1975, 97, 3623. J. M. Howell, J. Amer. Chem. SOC.,1975, 97, 3930. R. R. Holmes, J. Amer. Chem. SOC.,1975,97, 5379.

62

Organophosphorus Chemistry

for four-membered rings, and for bicyclic structures, and is thus in accord with recent observationsQ0 of square-pyramidalgeometry for the structures (74), (75), and (76). Gas electron-diffractionstudieson the phosphoranes(77)and (78)have revealed that the former has a regular TBP structure with axial CFI groups, while the latter has a distorted TBP

(CF,), PC1 -,

Cl,PCH=C(Mc)

N,=C=O

(79)

(77) n = 2 (78) n = 3

Stability calculationson the phosphoranes (79)have appeared.71Various potential functions for phosphorus pentafluoride (73; It = 0) have been r e ~ o r t e d An .~~~~~ e.s.r. study of y-irradiated phosphorus pentachloride has been published.74 New thermochemical data on phosphorus pentabromide have appeared.75 Preparation of Phosphoranes from Phosphorus(II1) Compounds.-Benzoylphosphoranes have been made from xenon difluoride, as shown for (80).76The barrier to rotation of the benzoyl group in (80)is found to be below 8 kcal mol-l, although 0

IIIt PhCPMe, + XeF,

F _t

F

evidence was obtained that at - 100 "C the benzoyl group preferred to be in the equatorial plane. Spirophosphoranes bearing a benzoyl group at phosphorus have been prepared as shown for (81), and an n.m.r. method has been used to estimate the barrier to axial placement of the benzoyl The value of AGS (20.9 kcal 6g

70

71 79

73

'*

75

76

For a recent discussion see R. R. Holmes, J. Amer. Chem. Suc., 1974, 96,4143. H. Oberhammer and I. Grobe, 2. Nuturfursch., 1975, 30b,506. A. A. Kisilenko, Yu. P. Egorov, E. A. Stukalo, and L. N. Markovskii, J. Gen. Chem. (U.S.S.R.), 1975,45, 1688. L. S. Bernstein, J. J. Kim, K. S. Pitzer, S. Abramowitz, and I. W. Levin, J. Chem. Phys., 1975, 62, 3671. L. S. Bernstein, S. Abramowitz, and I. W.Levin, J. Chem. Phys., 1976, 64, 3228. S. P. Mishra and M. C. R. Symons,J.C.S. Dalton, 1976, 139. A. Finch, P. J. Gardner, P. N. Gates, A. Hameed, C. P. McDermott, K. K. Sengupta, and M. Stephens, J.C.S. Dalton, 1975, 967. S. Trippett and P. J. Whittle, J.C.S. Perkin I, 1975, 1220.

Halogenophosphines and Related Compounds

63

mol-l) suggests that the benzoyl group has an apicophilicity comparable to that of the phenoxy-group. Details 77 have appeared of the synthesis of fluorophosphoranes containing fourmembered rings,78 and extensive variable-temperature n.m.r. studies have been described. Thus, for the phosphorane (82), the most stable conformations are (83) and (84), which inconvert to a minor conformer (85), via the intermediate (86).77

This work provides further evidence that axial placement of phenyl accompanied by equatorial placement of fluorine is costly in energy, while diequatorial siting of a fourmembered ring containing only carbon and phosphorus is considerably easier.7 7 Preparative details and extensive Lr., n.m.r., and mass spectra have been described for the phosphoranes (87)?6 These phosphoranes have a TBP structure, and for (87a)-(87c) their n.m.r. spectra are temperature-independent, and indicate that the fluorines bonded to phosphorus are equivalent. The authors have suggested an explanation based on rapid intramolecular isomerization, and discussed the possibility that a facile TR pathway exists for this process.46Octahedral adduct formation between (87) and fluoride ion or trimethylphosphine has also been de~cribed,*~ as shown in (88).

(87) a; R Me b; R = But

c;R=F%

-

d; R = F e; R NEt, f ; R = N(SiMe3),

(88)

Allyltrifluorophosphorane(89) may be prepared as shown, and the n.m.r. spectrum of (89) indicates a TBP structure.21A similar route has been used to prepare the analogous arylphosphoranes (go), which have been found to be quite stable, and

RPBr, + 3HF

*

“-J-R FI‘

F

(89) R = ally1 77 78

RPCL,

+ 3HF

RP(F,)H (90) R = aryl or alkyl

N. J. De’ath, D. B. Denney, D. Z. Denney, and Y.F. Hsu, J. Amer. Chem. SOC.,1976,98,768. N. J. De’ath, D. Z . Denney, D. B. Denney, and C. D. Hall, Phosphorus, 1974,3 205.

64

Organophosphorus Chemistry

isolable in good yields.44The novel di-iodophosphorane (51) has been isolated; see Section 1. Addition of chlorine to tris(amin0)phosphines has been used to prepare the dichlorophosphoranes (91), although the corresponding reaction of dialkylaminoAnalytical data, but no (dipheny1)phosphines (92) gave less stable spectra, have been described for (91).79

Preparation of Phosphoranes by Exchange Methods.-A convenient procedure has been developed for the one-step synthesis of chlorotetrafluorophosphorane(93).** The phosphorane (94) has been prepared as shown.s1Ring opening of the disilacyclobutane (95) by phosphorus pentafluoride affords the bisphosphorane (96), characterized by its spectra.82

Details have been published of the synthesis and spectra of a wide range of monoalkoxyphosphoranes (97), prepared by the silane-exchange method as The 19Fn.m.r. compilation on these phosphoranes is very impressive, and their structures

F MePF,

+ ROSiMe,

M e .. _+

I

Ro'T-F F (97)

79

8o

81 82

83

R*OP(R) F,

Bu*PF,

Et(Ph)PF,

(98) R* = chiralalkyl

(99)

(100)

A. M. Pinchuk, A. P. Marchenko, I. N. Zhmurova, and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1002. R. H. Neilson and A. H. Cowley, Znorg. Chem., 1975,14,2019. H. B. Stegmann, H. V. Dumm, and K. B. Ulmschneider, Tetrahedron Letters, 1976, 2007. W. Althoff, M. Fild, H. Koop, and R. Schmutzler, J.C.S. Chem. Comm., 1975,463. J. G. Riess and D. U. Robert, Bull, SOC.chim. France, 1975, 425.

Halogenophosplzines and Related Compounds

65

have been discussed in terms of TBP geometry for structures undergoing BPR isornerizati~n.~~ The same group have provided further n.m.r. data on a large number of alkoxyfluorophosphoranes(98), in which the fluorines are non-equivalent due to a chiral centre in the alkyl group of (98).84The phosphoranes (99) and (100) have been prepared for the first time.84 Reactions of Phosphoranes.-The reactions of phosphorus pentachloride (101) with simple organic molecules continue to attract attention, notably in the Russian literature. For example, the preparative uses of alkene-addition reactions of (101) have been examined for a-methylstyrene (102), as outlined in Scheme 7.85

a y p M” e>CHp

pcZ + PhC(Me)=CH,

&

-% Me\/C=CHPC1,

cl P(mHaCWV,

Ph (101)

-P(OR),

(102)

-

Reagents: i, mix reactants; ii, PCb-Sb; iii, /-\;iv, 2 ‘ O / ; v, ROH-base.

Scheme 7

Kinetic studies of alkenephosphorus pentachloride reactions in benzene show the effects of substituents when the double bond is terminal.86When the alkene is conjugated, the standard work-up conditions (using sulphur dioxide) produce alk-lenylphosphonyl dichlorides (103), instead of 2-chloroalkylphosphonyl dichlorides (104). 0

0

RCH=CH,

+ pcz

wo~:up

(101)

+

II RCH-CHPCL, (103)

R = arylor

ll

or RCHC~CH~FQ (104)

R = -1

alkenyl

Me

I &COH

+ pcZ (101)

(1W 84 85 86

-+

a 0 I II

&CCHPc1, (18%) (105)

(retained confguration)

D. U. Robert, D. J. Costa, and J. G. Riess, Org. Magn. Resonance, 1975, 7 , 291. V. V. Konnachev, L. V. Krylov, and V. A. Kukhtin, J. Gen. Chem. (U.S.S.R.), 1975,45,2327. V. G. Rozinov. V. V. Rybkina, E. F. Grechkin, and A. V. Kalabina, J. Gen. Chem. (U.S.S.R.), 1975,45, 1609.

V. G. Rozinov, V. V. Rybkina, E. F. Grechkin, and A. V. Kalabina, J . Gen. Chem. (U.S.S.R.), 1975,45, 1610.

Organophosphorus Chemistry

66

The formation of 2-chloroalkylphosphonyldichlorides (105) from tertiary alcohols and (101) has been ascribed to the intermediate formation of alkenes, as showmas Tertiary alcohols are chlorinated by (101), in a mild, efficient procedure which usually occurs with retention of config~ration,~~ as for (106). The reaction between benzyl cyanide (107) and phosphorus pentachloride (101) has been shown to be dependent on both solvent and t e m ~ e r a t u r e .This ~ ~ allows a rationalization of the century-old result of C l a i ~ e nwho , ~ ~isolated the gem-dichloride (108) from this system, while later workers O2 obtained the phosphorimidic derivative (109) instead. The present studyg0describes the isolation of (110), an intermediate in the formation of (109), and distinguishes conditions leading to (110) from those producing (108).

Several papers have been devoted to the subject of reactions of phosphoranes with carboxylic acids and their derivatives. Thus triphenylphosphine dibromide (1 11) in acetonitrile cleaves lactones,03 while the corresponding dichloride (1 12) converts esters into acid chlorides.94 The reactions of esters with phosphorus pentachloride (101) have been studied further,95and the influence of structural changes on the yields of products (1 13) and (1 14) has resulted in minor modifications to the mechanism previously 96 outlined. Ph,PBr2

(111)

+

0

0

:

("' C0,Me

Phosphorus pentachloride (101) chlorinates amides, and the products (1 15) can be reductively dehalogenated with sodium borohydride, thus providing a two-step V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov. J. Gen. Chem. (U.S.S.R.), 1974, 44, 2573. 8 9 R. M. Carman and I. M. Shaw, Austral. J. Chem., 1976, 29, 133. N. D. Bodnarchuk and V. I. Kal'chenko, J. Gen. Chem. (U.S.S.R.),1975,45, 1007. 91 L. Claisen, Ber., 1879,12, 626. 92 E. Fluck and W. Steck, Phosphorus, 1972, 1, 283. 93 E. E. Smissman, H. M. Alkaysi, and M. W. Creese, J. Org. Chem., 1975, 40, 1640. 94 D. J. Burton and W. M. Koppes, J. Org. Chem., 1975,40, 3026. 95 V. V. Moskva, V. M. Ismailov, S. A. Novruzov, A. I. Razumov, T. V. Zykova, Sh. T. Akhmedov, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.),1974, 44, 2574. g6 V. V. Moskva, V. M. Ismailov, S. A. NOVNZOV, A. I. Razumov, T. V. Zykova, Sh. T. Akhmedov, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.),1973, 43, 2071. 88

Halogenophosphinesand Related Compounds

67

conversion of amides into amines.97 The stepwise chlorination of N-cyclohexylacetamide (116) by phosphorus pentachloride (101) has been studied as a model for acetamido-s~gars.~~ Phosphorus pentachloride (101) and tfiethylamine cyclize the amide (117).O@ 0

II

RTH,CNR:

('01) :

R'CH=C(CI)NR;

NaBH,

RICH,C&NR~

OEt PCI,

NHCOPh

+ Et,N

EtOH

+ HCIL

Cyclic 1,3-diketones have been converted into p-halogeno-ketones (1 18) by triphenylphosphine dihalides in benzene or acetonitrile,lOO although this paper adds little to previous work lol in this field. The reactions of phosphorus pentachloride with acetals have been extended to mixed acetals, such as (119).loaOnly one product

(118) X = C1,91%

,OEt MeCH 'OPI'

(i) PCI, (101) (ii) SO,

0 i~

II

PCH=CHOP~~ 82%

(119) A. Rahman, A. Basha, N. Waheed, and S. Ahmed, Tetrahedron Letters, 1976, 219. A. M. Dempsey and L. Hough, Carbohydrate Res., 1975,41, 63. gs B. S. Drach and 0. P. Lobanov, J. Gen. Chem. (U.S.S.R.),1974,44,2730. looE. Piers and I. Nagakura, Synth. Comm., 1975, 5, 193. 101 J. A. Miller in 'Organophosphorus Chemistry', ed. S. Trippett, (Specialist Periodical Reports), The Chemical Society, London, 1973, Vol. 4, pp. 65, 66. 102 V. V. Moskva, T. Sh. Sitdikova, A. I. Razumov, T. V. Zykova, R. A. Salakhutdinov, and G. F. Nazvanova, J. Gen. Chem. (U.S.S.R.),1975,45, 1462. 97

98

Organophosphorus Chemistry

68

is obtained in this reaction, in good enough yield to suggest that this type of transformation may yet be of general synthetic utility. Synthetic Uses of Phosphine-Halogenocarbon Reactions.-This is a field which has attracted an increasing amount of effort in recent years, largely due to the extensive studies by Appel and his colleagues. Much of this work is summarized in a review lo3 which covers the principles and synthetic applications of reactions involving a tertiary phosphine and carbon tetrachloride. Despite the interest generated by this work, little is known about the mechanistic aspects of these reactions, although one might not appreciate this from some of the current papers in the area. This year has witnessed three independent attempt^^^^-^^^ to rectify this situation, and overall a fair measure of agreement can be seen in the conclusions. The first paperlo4is devoted to a study of the intermediates formed in reactions of triphenylphosphinecarbon tetrachloride with compounds possessing acidic hydrogens. Thus the initial interaction of triphenylphosphine (120) with carbon tetrachloride yields the ylide (121) and the phosphorane (112), which, in the presence of protic species (such as ROH in Scheme 8), react further to give the salt (122) and triphenylphosphine oxide. A recycling sequence then converts (122) into the dehalogenated salts (123) and (124), respectively,lo4as shown in Scheme 8. 0 2Ph,P + CCl, --+

(120)

II

Ph,P + Ph3$CHC1, Cl- + RC1

Ph,PCl, + Ph,P=CCl,

(1 12)

(121)

(122)

0

(122) + Ph,P

_.)

II f

A Ph,P

Ph,PCl, + Ph,P=CHCl (112)

Ph,kH,ClCl-

+

RC1

(123)

0

(123)

+

II

Ph,P -k ROH -+ Ph,P + Ph,kH,

a + RCl

(124) Reagent: i, ROH.

Scheme 8

Of these steps, the last is often not observed in practice, although the authors have demonstrated its efficiency by treating triphenylphosphine (120) and the salt (123) with cyclohexan01,1~~ to give the products indicated in Scheme 8. A related studylo5 using dibromodifluoromethane (125) gave similar results, although the authors concentrated on demonstrating the equilibrium between the salt (126) and the derived ylide. The species involved in this equilibriumlo5were either isolated or trapped, as shown by the dotted arrows. R. Appel, Angew. Chem. Internat. Edn., 1975, 14, 801. I. Tomoskozi, L. Gruber, and L. Radics, Tetrahedron Letters, 1975, 2473. lo5 D. G. Naae, H. S. Kesling, and D. J. Burton, Tetrahedron Letters, 1975, 3789. l 0 6 R. Appel, F. Knoll, W. Michel, W. Morbach, H.-D. Wihler, and H. Veltmann, Chem. Ber., 1976,109, 58. 1°3

lo4

69

Halogenophosphines and Related Compounds 2Ph,P + CF,Br,

T Ph,kBrF, + Ph,P -xel+ salt (85%)

Br-

(125)

The third paper in this group106is concerned with the isolated triphenylphosphinecarbon tetrachloride system, and the authors show how these compounds react only in the presence of small amounts of polar impurities, to produce initially the salt (127), which is rapidly converted into (121), as shown in Scheme 8. In the absence of protic material, the ylide (121) reacts further,loSas shown.

Ph,hC(Cl) =PPh,

C1'

Preparative applications of these reactions have included work on peptide synthesis from amino-acids (suitably protected) using triphenylphosphine(120) lo8 or a polymer-bound aryldiphenylphosphine (128).lo9Coupling is generally very efficient,lo7but racemization problems occur in some reactions.1o8,logA typical coupling reaction using (128) is outlined in Scheme 9.

R2

R' polymer

...ArPPh,

I

+ ZHNCHC0,H + HzNd€IC.O2R3,HX

(128)

R'

I

R2

I

ZHNCHCONHCHC02R3

(70-76s) Reagent : i, CC14-EbN.

Scheme 9 R. Appel, G. Baumer, and W. Struver, Chem. Ber., 1975, 108, 2680. R. Appel, G. Baumer, and W. Struver, Chem. Ber., 1976, 109, 801. lo* R. Appel, W. Struver, and L. Willms, Tetrahedron Letters, 1976, 905. 1°7

70

Organophosphorus Chemistry

Other 110-114 synthetic uses of these reactions are summarized in Scheme 10. 0

0

R,POH

(&P)zO

II

I1

ref. 110

(PhP), + CCI, -+ PhP(Cl)CC13

ref. .111

70%

(RP),

+

cct

--

R -- cyclohesyl

R~PPR: + 3 c c 4 + SR:NH

~

RP(Cl)P(CCl,) R

R$(NR;),cI-

ref. 111 ref. 112 ref. 113

X X = lonepairandx = 0 Ph,P + HXPh & Ph,$XPh Cl'(97%)

ref. 114

X = OorS Reagents: i, Ph3P-CCLP-Et3N; ii, CCL-EtaN.

Scheme 10

Miscellaneous.-Hydridofluorophosphates have been prepared for the first time, and the anion (129) has been found to have an octahedral structure, with hydrogens trans.l15 Phosphorus pentafluoride forms an adduct with biscyclopentadienyl titanium difluoride.lleThe phosphorane (1 30) has been prepared as ~h0wn.l~'

Mi

110

113 114 115 116 117

R. Appel and H. Einig, Z . anorg. Chem., 1975, 414, 236. R. Appel and R. Milker, 2. anorg. Chem., 1975,417, 161. R. Appel and R. Milker, Chem. Ber., 1975, 108, 2349. T. Ohashi and R. Appel, Bull. Chem. SOC.Japan, 1975,48, 1667. R. Appel, K. Warnung, and K.-D. Ziehn, Annalen, 1975,406. K. 0. Christe, C. J. Schack, and E. C. Curtis, Inorg. Chem., 1976, 15, 843. H. C. Clark and A. Shaver, J. Coordination Chem., 1975,4, 243. E. S. KOZIOV, S. N. Gaidamaka, and L. I. Samarai, J. Gen. Chem. (U.S.S.R.),1975, 45, 458.

4 Phosphine Oxides and Sulphides BY J. A. MILLER

1 Preparative Aspects Reviews have appeared on synthetic uses of a-diazoalkylphosphoryl compounds,1 and on the synthesis and complexing properties of alkylenediphosphine dioxides2 The diversity of the reactions of a-diazoalkylphosphineoxides is further demonstrated by work from Regitz's Treatment of diazomethyldiphenylphosphine oxide with aldehydes yields the oxides (l), which have been converted into a range of other oxides3as shown. 0

0

II

I1 PbPC(N,) CH(0H)R

RCHO 7

0

=- PbPCHR CHO

0

ll Ph,PCH$OR

I1

WPC-CR

0

II

Compounds possessing a 'PH

/

part-structure undergo a general condensation

reaction, leading to a-aminoalkylphosphorylproducts (2), with amines and carbonyl compounds. A critical analysis of previous mechanistic interpretation of this reaction has a ~ p e a r e dEarly . ~ study of such systems has suggested6that a-hydroxyalkylphosphoryl intermediates were involved (path a), although an attractive alternative view was that a-amino-alcohols were involved (path b), as shown in Scheme 1. The present work4 confirms that path b holds for R = CH,Ph or OBun. Although the first step of path a is fast for R = CH2Ph, it is easily reversed as the temperature is increased, and path b is still the predominant route to (2). 1 2

5 6

M. Regitz, Angew. Chem. Internat. Edn., 1975, 14, 222. T. Ya. Medved, Yu. M. Polikardov, L. E. Bertha, V. G. Kossykh, K. S. Yudina, and M. I. Kabachnik, Rum. Chem. Rev., 1975,44,468. W. Disteldorf and M. Regitz, Chem. Ber., 1976, 109, 546. K. A. Petrov, V. A. Chauzov, and T. S. Erokhina, J. Gen. Chem. (U.S.S.R.),1975,45, 727. M. 1. Kabachnik and T. Ya. Medved, Doklady Akad. Nauk S.S.S.R., 1952,83,689; 1952,84, 717. E. K. Fields, J. Amer. Chem. SOC.,1952,74, 1528.

71

72

Organophosphorus Chernistry 0

II I I

R;P -COH P a t h y

R'

\II PH + \C=O /

R'.

+

/

R2NH,

\

path h

OH

0

II

\I C-NRZ ' I H

I I

GP-CNHR~ (2 1

0

I1

Reagents: i, R2NH2; ii, RiPH

Scheme 1

Ferrocenylphosphines and their oxides (3) have been prepared by standard routes,' and the properties of diferrocenylphosphine oxide (3; n = 2) reported.8 Derivatives of diphenyl(ferrocenylmethy1)phosphine oxide (4) have been prepared by a metallation-alkylation ~equence,~ as shown for the oxide (5). 0

(i) BuLi X 2 (ii) BrCH,CH,Br

II PhzPCH2Fc

0

(4 1

(3) F c = ferrocenyl

Fc (5 1

MePC1,

(i) (ii) MeOH b

Q

+

/ \ Me 0

Q

/ \ Me

0

Synthetic studies of various cyclic phosphine oxides continue to be published. Thus a methanolic work-up leads to an 88% yield of 1-methylphospholen 1-oxides (6) from dichIoro(methyl)phosphine, and detailed slP n.m.r. and mass spectra have been described.l O The oxides (7)and (8) have been prepared l1 as shown. Structural

*

A. N. Nesmeyanov, V. D. Vil'chevskaya, A. I. Krylova, Yu. S. Nekrasov, and V. S. Tolkunova, Bull. Acad. Sci., U.S.S.R.,1975, 706. A. N . Nesmeyanov, V. D. Vil'chevskaya, A. 1. Krylova, and V. S. Tolkunova, Bull. Acad. Sci.,

U.S.S.R.,1975, 1710. G. Marr, B. J. Wakefield, and T. M. White, J. Organometallic Chem., 1975,88, 357. lo K. Moedritzer, Synth. React. Inorg. MetaLOrg. Chem., 1975, 5, 299. l1 F. Mathey and D. Thavard, Compt. rend., 1975,281, C , 243.

73

Phosphine Oxides and Sulphides

studies have appeared on the products (9) formed by cycloaddition of phenylphosphine to the dienone (10).l2Recent years have seen a number of preparations of A2-phospholenl-oxide (11) based on enone additions, and this type of reaction has now been directed towards the synthesis of heterocyclic ~ter0ids.l~

Ph

-0

+

*

PhPH,

+ epimer

0

d

0

‘Rl

(11)

Polyphosphoric acid (PPA) (115 %) has been used in a very convenient preparation of phosphindoline l-oxides and phosphinoline l-oxides by cyclization of various alkenylphosphine oxides (12).14 Isophosphindole oxide (13) has been preMe

1

Ph,PR (12)

R = 180°C 115% PPA

(

ally1

\

R = crotyl or R = but3-eny1

Me I

J. R. Wiseman and H. 0. Krabbenhoft, J. Org. Chem., 1976,41, 589. R. Bodalski, K. M. Pietrusiewicz, and J. Koszuk, Tetrahedron, 1975, 31, 1907. l4 M. El-Deek, G. D. Macdonell, S. D. Venkataramu, and K. D. Berlin, J. Org. Chem., 1976,41, la

1403.

Organophosphorus Chemistry

74

Ph

H

Reagents:. i, NBS; ii, base; iii, MeO,CC=CCO,Me;

iv,

0

; v,

-

Scheme 2

pared as shown in Scheme 2, and Diels-Alder adducts have been obtained with a number of dienophiles.ls Epoxidation of 1-methyl-As-phospholen 1-oxide (6b) yields essentially one isomer (Scheme 3), whose stereochemistry has been confirmed by 13Cn.m.r. studies.16

u -0

/ \Me 0

perocid

~

//

0

’\\

Me

(6b) Scheme 3

Various &substituted vinylphosphine oxides (14) have been made by the Wittig route, and found to be trans-isomers.’? The geometry of these oxides is believed to be 0

0

0

ll II Ph,PCH,P(OPh), + RChO

Wittig k

It

Ph,PCH=CHR

determined by steric effects operating in the transition state for the cyclization step.17 Polyene formation by Wittig reactions of the oxide (15) has been described (Scheme 4).18 l5 l*

l8

T. H. Chan and K. T. Nwe,Tetrahedron, 1975, 31,2537. C. Symmes and L. D. Quin, Tetrahedron Letters, 1976, 1853. D. Gloyna, K. G. Bernot, H. Koeppel, and H. G. Henning, J. prakt. Chem., 1976,318,327. B. Lythgoe, T. A. Moran, M. E. N. Nambudiry, S. Ruston, J. Tideswell, and P. W. Wright, Tetrahedron Letters, 1975, 3863.

75

Phosphine Oxides and Sulphides

Reagents: i, C l d C O C l ; ii, Ph,PLi; iii, H,O,;, iv, Wittig reaction '

Scheme 4

Perfluoroalkylphosphine oxides have been reported to show some interesting surface-active properties. Examples of the synthesis of such oxides are given for (16) and (17).la The oxides (18)*O and (19)21have been prepared by standard routes.

R

0

I1

Me,PH + CH,=CHR,

Me,PCH(Me)R,

*IBN*

RF = perfluoroalkyl Ph,kH=CHCOMe

+' (16)

(17)

:;$+

Ph,PCH(Ph) CH,COMe (18)

Ph,POEt + CH,-CHCH,Br \

/

_j.

(19) 25%

' 0 '

Details have appeared of the conversion of chiral phosphine sulphides (20) into the corresponding inverted oxides, and a rationalization of the stereochemistry has been

S

11

Ph,PSR (22)

(i) BuLi (ii) MeI+

S

11 Pb,PMe

+ RSBu

Ph,PPPh,

(21)

(i) R ~ M Q (ii) S,

*

S

II

PbPC(R)Me, (23) R = CN (24) R = C0,Me

Is

M. Demarcq and J. Sleziona, J. Fluorine Chem., 1975, 6, 129.

20

M. M. Shevchuk, S. T. Shpak, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.),1975, 45, 2 109. A. P. Rakov, E. A. Kosterin, and G . F. Andreev, J. Gen. Chem. (U.S,S,R.), 1975, 45, 1726.

2l

76

Organophosphorus Chemistry

suggested.22An unusual preparation of phosphine sulphides (21) from the phosphinodithioates (22) has been d e s ~ r i b e d The . ~ ~ authors provide evidence that the metal alkyl attacks the ester (22) at sulphur, and that the formation of (21) is the result of a subsequent a l k y l a t i ~ n .The ~ ~ sulphides (23) have been prepared from tetraphenyldiphosphine (24).24 2 Addition Reactions of R,P(X)H The confusing subject of a-keto-phosphine oxides has entered the literature again. Thus the group which originally misassigned the structure of the product formed by trifluoroacetic acid and chlorodiphenylphosphine (25) has now agreed 2s with the revised structure (26) suggested last year.26The key step in the formation of (26) is believed to involve addition of diphenylphosphine oxide (27) to trifluoroacetylphosphine oxide (28), to give (29), although the authors do not rule out the possibility of direct formation of (26).25However, an independent study 27 of the oxidation of trifluoroacetylphosphine(30) shows how the 2: 1 adduct (29) is formed initially [by addition of (27)?], and how contact with glass causes rapid isomerization to (26). Once again, the reversible formation of (29) remains an unanswered aspect of the pathway to (26). 0 CF3C0,H + Ph,PCl

II

Ph,PCOCF,

A further illustration has appeared28of the reactivity of simple a-keto-alkyldiphenylphosphine oxides (31) towards addition reactions, as outlined in Scheme 5. In the same paper, alkylation of chloro(di-t-buty1)phosphine (32) by alkyl benzoates is described see Chapter 3 for details. A similar acylation reaction of tetramethyldiphosphine disulphide (33) has been described, although the acetylphosphine sulphide (34)was not 22

23 24 25 26 27

28 29

R. Luckenbach and M. Kern, Chem. Ber., 1975, 108, 3533. K. Goda, R. Okazaki, K. Akiba, and N. Inamoto, Tetrahedron Letters, 1976, 181. R. Okazaki, Y.Hirabayashi, K. Tamura, and N. Inamoto, J.C.S. Perkin I, 1976, 1034. P. Sartori and R. H. Hochleitner, Z. Naturforsch., 1976, 31b. 76. D. J. H. Smith and S. Trippett, J.C.S. Perkin I, 1975, 963. E. Lindner, H.-D. Ebert, and H. Lesiecki, Angew. Chern. Internat. Edn., 1976, 15, 41. N. J. De’ath, S.T. McNeilly, and J. A. Miller, J.C.S. Perkin I , 1976, 741. A. N. Pudovik, G. V. Romanov, A. A. Lapin, and E. 1. Gol’dfarb, J. Gen. Chem. (U.S.S.R.), 1975,45, 1857.

-

Phosphine Oxides and Sulphides Ph,POMe

+ RCOCl

0

77

+ MeCl

Ph,P(O)COR (31)

0

0

I1 II Ph,PC(R)OPPh,

ll

+

I XI

(Ph;P),C

R = AcorH

0

0

ll + RPBut2

S

1

+

R = Me or benzyl

I1 (Me,P),

R,PBwt R = benzyl S

S

f

MeCOC1

\

\OR

R = MeorPh, X = H R = Ph, X = COPh Scheme 5

Bu',PCk + PhC0,R

/Me

:ty*.*

II Me,PCOMe

(33)

II

+ Me,PCl

(34)

0

II Bu,PH

0

I/ + MeCCN

0 ._)

0

ll Ph,PH

II

Bu,POCH(Me)CN

78%

0

+ R'N=NC0,R2

ll

Ph,PNR'NHC0,R2

(36)

Addition reactions of secondary phosphine oxides to acetyl cyanide (35),30 and to azo-esters (36),81have been described. Complexes of dimethylphosphine sulphide (37) with manganese pentacarbonyl derivatives, in which the new ligand is bonded through sulphur, have been isomerized to complexes in which phosphorus is bonded to the 30

T. M. Sudakova, E. Kh. Ofitserova, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.),1975, 45. 25 12.

31 32

K.-H. Linke and W. Brand, Angew. Chem. Internat. Edn., 1975, 14, 643. E. Lindner and H. Dreher, Angew. Chem. Internat. Edn., 1975, 14,416.

78

Organophosphorus Chemistry

3 Reactions involving P-C Bond Cleavage The phosphine oxide (38) is known to undergo nucleophilic substitution reactions with cleavage of either a phosphorus-phenyl bond, or one of the heterocyclic 0 N - H H*

pJL-?

Ph

+PhH

phosphorus-rbon bonds.ss These processes have now been suggested to depend upon the apicophilicity of the incoming nucleophile (N), as shown for hydride and hydroxide nucleophiles.33 Primary amines react with benzylbis(a-hydroxybenzy1)phosphine oxide (39) to give a-aminoalkylphosphine oxides (40) and (41),34 and the reaction has been 0

It PhCH,P(CHOHPh),

0

II

PhCH,PCH(OH)Ph

bag*

H

I-

(39)

+ PhCHO bNH*

PhCH=NR

'II /

CH(0H)Ph

PhCH,P(CH(NHR) Ph), +repe'

--

PhCH,P

\

CH(Ph) NHR

(40) 88 84

I. Granoth, Y. Segall, and H. Leader, J.C.S. Chem. Comm., 1976, 74. A. B. Pepperman and T. H. Siddall, J. Org. Chem., 1975,40, 1373.

79

Phosphine Oxides and Sulphides

shown34,36to involve release of benzaldehyde from (39), and subsequent addition of the secondary phosphhe oxide to benzalimine. A similar reaction forms the basis of the explanation proposed for the production of (42) from (39).36 Details of various routes to allylphosphineoxides (43) have been reported, and the subsequent synthesis of lY3-dieneshas been illustrated by many examples.37Also described are stereochemical aspects of these diene syntheses and of subsequent Diels-Alder cycloaddition reaction^.^' High regioselectivity is observed in migrations of the diphenylphosphinoyl group from unsymmetrical sites, as in (44),in that both products have a double bond exocyclic to the cyclohexane ring.38 0

I/

Ph2P--c/

‘c=o \ +/

CE;CO,H

\R

P h P ally1

Wittig

dienes

0

I1

Ph,PCl + RMgX

*OH (44)

PPh,

II 0

PPh,

II

0

4 Reactions of X in the P=X Group Migration of sulphur from one phosphorus to another has been when the sulphide (45) is heated. The intermediates(46) and (47) have been detected. Debenzylation of the phosphine sulphide (48) has been shown to be accompanied by a desulphuration, which is believed to result from the interaction of (49) with alkaline DMS0.40 s6 36 87

s8 s8 40

A. B. Pepperman and T. H. Siddall, J. Org. Chem., 1975,40, 2053. A. B. Pepperman, G. J. Boudreaux, and T. H. Siddall, J. Org. Chem., 1975,40,2056. A. H. Davidson and S. Warren, J.C.S. Perkin I , 1976, 639. A. H. Davidson and S. Warren, J.C.S. Chem. Comm., 1976, 181. S. 0. Grim and J. D. Mitchell, J.C.S. Chem. Comm., 1975, 634. R. Luckenbach, Tetrahedron Letters, 1976, 2015.

Organophosphorus Chemistry

80 Ph2PCH,PMe, S

S

(46)

II Ph,FCH,PMe,

+ s

(45)

I1

Ph,PCH,PMe,

--+

s

II ll Ph,PCH,PMe,

Further examples of deoxygenation of epoxides by phosphine sulphides or selenides have appeared,4l as shown in Scheme 6 for simple epoxides (50). Incorporation of phosphorus into a five-membered ring appears to be responsible for the relatively rapid deoxygenations by the phosphole and A3-phospholen derivatives.4l

X = S orSe Reagents: i,

Melr-JMe /

PI1

;

X = Sor Se

(50)

.. Me[-=Me

11,

x/

\

Ph

Scheme 6

Several examples have been reported of rearrangements of arsine oxides (51) to esters, initiated by alkyl 43 Reactions of tertiary arsine oxides with thiols (52) cause de~xygenation.~~ 0

II Ph,AsR’

.O

+ R’X

--+

Ph,AsOR2 + R’X

II

R ~ A s+ R’SH

R2SSR2 + R:As

+

H,O

5 Reactions of the Side-chain Further bisalkynylphosphine oxide (53) cyclizations have been applied to heterocyclic synthesis.46The phosphine oxide (54) has been prepared as shown, and found to undergo Diels-Alder addition by an intramolecular pathway, to give (55).46 41

42 43 44

45

4G

F. Mathey and G . Muller, Compt. rend., 1975, 281, C, 881. Yu. F. Gatilov, B. E. Abalonin, and Z . M. Izmailova, J. Gen. Chern. (U.S.S.R.), 1975, 45, 42. Yu. F. Gatilov, B. E. Abalonin, and Z . M. Izmailova,J. Gen. Chem. (U.S.S.R.),1975,45,2145. N. A. Chadaeva, K. A. Mamakov, and T. V. Arsent’eva, Bull. Acad. Sci., U.S.S.R.,1975,1715. A. Naaktgeboren, J. Meijer, P. Vermeer, and L. Brandsma, REC.Trav. chim., 1975, 94, 92. 0. Schaffer and K. Dimroth, Angew. Chern. Znternat. Edn., 1975, 14, 112.

81

Phosphine Oxides and Sulphides

A0

(5 3)

R'

X = 0,S,or NEt Ph. ,H,CH=CD, 110°C

I

Ph

/ \OCDaCH=CHL

Me

/A \0

Me

p

31

D

CD

Me (55)

Ph

Me '0 (54)

Aromatic substituent effects due to phosphorus groups have been studied for a number of reactions.47Thus ester hydrolysis and fluoride-displacement rates, for (56) and (57) respectively, are enhanced by phosphorus substituents (X = 0 or :), while the rate of hydrolysis of the halide (58) is enhanced for X = :, but slowed for X = 0.47 A perturbation M.O. analysis of these observations has been p r e ~ e n t e d . ~ ~

(56) R = C0,Me (57) R = F

(59) n = 0 or n = 1

(58) R = CHClMe

(60)

Nitration of various p h e n ~ l - *and ~ benzyl-phosphineS0 oxides (59) has been described, and the P=O group found to be meta-dire~ting~~ in the former case. Pyrolysis of the acyl azide (60)61takes the course shown.

50

B. Klabuhn, H. Goetz, P. Steirl, and D. Alscher, Tetrahedron, 1976, 32, 603. B. Klabuhn, Tetrahedron, 1976,32, 609. E. Malinski, A. Piekos, and T. A. Modro, Canad. J. Chem., 1975,53, 1468. V. V. Kormachev, T. V. Vasil'eva, B. 1. Ionin, and V. A. Kukhtin, J. Gen. Chem. (U.S.S.R.),

51

V. A. Shokol, V. V. Doroshenko, and G . I. Derkach, J. Gen. Chem. (U.S.S.R.), 1975,45, 1680.

47 48 49

1975, 45, 293.

82

Organophosphorus Chemistry

6 Miscellaneous Physical and Structural Aspects Extensive 13Cand slP n.m.r. studies have been reported for phosphine oxides and selenides, and the inversion-recovery technique has been used to establish 2J and *J values for 1sG31Pcoupling.62Shift reagents have been used to establish alkene geometry in the oxides (61).53Coupling and shift data have been published for the arylphosphine derivatives (62).64 0

X

ll

Ar,P

(62) Ar = 4-chlorophenyl or 3-chlor ophen yl x = - , 0, S, or Se

X

X

II Me,P

II

Ar,P

(63) a; X = 0 b; X =

-+, S,

or Se

(64) a; X = S or Se b ; X = 0,

Torsional barriers for trimethylphosphine derivatives (63) have been obtained from Raman spectra.66Vibrational spectra for the uranyl nitrate complex of (63a) have been published.66Complexes of triarylphosphine derivatives (64) with iodine,67 and of (64b) with metal halidesYs8 have been the subject of therrnodynami~~~ and spectroscopicti 7, 68 study. X-Ray data have been published for Ah"-phospholenl-oxide (65),60tri-o-tolylphosphine derivatives (66),*O and various halogeno-alkylphosphine oxides.61

(66).X= 0, S, or Se (65)

Further study has been made of the ionization of the phosphinoyl-substituted acids (67), and the substituent at phosphorus has been found to be important in influencing acidity.62Evidence for cyclic solvates was found for (67;n = 1).62 The T. A. Albright, W. J. Freeman, and E. E. Schweizer, J. Org. Chem., 1975,40,3437. H.Koeppel, U. Lachmann, and K. D. Schleinitz, J. prakt. Chem., 1975,317,425. 54 R. F. De Ketelaere and G. P. van der Kelen, J. Mol. Structure, 1975,27, 25. 55 H.Rojhantalab, J. W. Nibler, and C. J. Wilkins, Spectrochim. Acta, 1976,32A,519. 56 Y. B. Kirillov, E. P. Buchikhin, K. I. Petrov, and T. V. Zagorskaya, Zhur. priklad. Spectroskopii, 1975,23,514. 57 F. Lux, R. Paetzold, J. Danel, and L. Sobczyk, J.C.S. Faraday 1 1, 1975,71, 1610. 5 8 E. G.Amarskii, A. A. Shvets, and 0. A. Osipov, J. Gen. Chem. (U.S.S.R.), 1975,45, 881. 59 D. van der Helm, D. M. Washecheck, J. E. Burks, and S . E. Ealick, Acta Cryst., 1976,B32,659. 60 T. S. Cameron and B. Dahlen, J.C.S. Perkin 11, 1975, 1737. 61 V. V. Saatsasov, T. L. Khotsyanova, and S. I. Kuznetsov, Bull. Acad. Sci., U.S.S.R.,1975,839. 62 E. N.Tsvetkov, R. A. Malevannaya, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1975,45, 706.

S2

53

83

Pliosphine Oxides and Sulphides

(67)

(68)

(69)

carbon acidity in diglyme or DMSO of phosphine oxides with general formula (68) has been evaluated by a transmetallation method.64A change of about eight pKa units results from introduction of the phosphinoyl group onto a hydrocarbon site.63 Substituent effects in the benzyl ring of (69) have been observed to influence acidity in the oxides (69),and a good correlation with 0- has been ~ b t a i n e d . ~ ~ The ability of phosphine oxides to enter into intermolecular hydrogen bonding has Since the dipole values of simple oxides been measured by i.r. and dipole (70a), (70b) fit a vector-addition model, the authors suggest that H-bonding is controlled by electrostatic interaction (and not by chargetransfer effects).66 On a related theme, the extracting powers of the oxide (70b) towards thiocyanic acids6 and of the oxide (70a) towards cationss7p68have been measured. The oxides (71) form cyclic complexes with titanium tetrahalides.6B 0 R,P=O (70) a; R = Me b; R = Bun c; R = n-octyl

0

II

(n-alkyl) PMe,

n-Alkyl(dimethy1)phosphine oxides (72) form micelles readily, and a study of the (unexpected) increase in entropy associated with micellization has been made.7b Acetoxymethylphosphine oxides have been investigated as starters in the synthesis of phosphorus-containing polyesters.71 The synthesis of azo dyestuffs containing phosphine oxide groups, as in (73), has been 63 64

s5 86

s7 68

70

72

S. P. Mesyats, E. N. Tsvetkov, E. S. Petrov, M. I. Terekhova, A. I. Shatenshtein, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R., 1974,2399. S . P. Mesyats, E. N. Tsvetkov, E. S. Petrov, N. N. Shelganova, T. M. Shcherbina, A. I. Shatenshtein, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R., 1974, 2406. Yu. Ya. Borovikov, Yu. P. Egorov, and A. A. Matei, J. Gen. Chem. (U.S.S.R.), 1975,45,2563. M. Zakharieva, Khim. i Znd., 1975,47, 66. J. W. Mitchell and J. E. Riley, Radiochem. Radioanalyt. Letters, 1975, 21, 41. M. Mojski and C. Poitrenaud, J. Radioanalyt. Chem., 1976, 29, 89. A. A. Shvets, 0. A. Osipov, 0. A. Moiseeva, and E. L. Korol, J. Gen. Chem. (U.S.S.R.), 1975 45, 1251. J. H. Clint and T. Walker, J.C.S. Faraday I, 1975, 71, 946. G. Borisov, S. G. Verbanov, E. N. Tsvetkov, and M. I. Kabachnik, Vysokomol. Soedineniya, Ser. A, 1975, 17, 1065. V. V. Kormachev, S. N. Chalykh, E. A. Chalykh, A. A. Sazanova, and V. A. Kukhtin, J. Gen. Chem. (U.S.S.R.), 1975,44,2575.

5 Tervalent Phosphorus Acids BY 8.J. WALKER

1 Introduction Although this chapter is somewhat shorter than last year's, it is encouraging to note that several papers have appeared which deal with the synthesis and chemistry of p,-bonded phosphorus compounds. 2 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-At tack on Saturated Carbon. Selected examples of the Arbusov reaction include phosphorylation of the chloroacetophenones (1) to give phosphonates, which cyclized to (2) in the presence of acid chlorides,l formation of the azodiphosphonate (3) from 2,2'-dichloro-2,2'-azopropane,2and the reaction of 2-chloro-3,4-dihydro-3-oxo-2H1,4-benzothiazine (4) with triethyl phosphite to give the 2-phosphonate (9, which is used as an o l e h synthon? Bis(trimethylsily1) trimethylsiloxymethylphosphonite(6) has been synthesized by silylation of hydroxymethylphosphonous acid, and, as expected, undergoes a normal Arbusov reaction with alkyl halides to give the phosphonates (7).4 This series of reactions, followed by 0

I1

PhCOCHClNHCOR'

II

EtOPR:

ph

I

(1 1

- PRi

n

PhCWHNHCOR'

0\2

K'

0

0

ll ll (E t O),PCMe,N=NCMe,P( OEt), (4)

(3)

x

= c1

0

/I

( 5 ) X = P(OEt),

2

B. S. Drach, I. Yu.Dolgushina, and A. D. Sinitsa, Zhur. obshchei Khim., 1975,45,1251 (Chem. Abs., 1975, 83, 131 688). E.g. Ya. A. Levin, I. P. Gosman, A. G. Abul'kanov, and B. E. Ivanov, Izoest. Akad. Narrk S.S.S.R.,Ser. khim., 1975, 983 (Chem. Abs., 1975, 83, 97469). J. W. Worley, K. W. Ratts, and K. L. Commack, J. Org. Chem., 1975, 40, 1731. A. F. Rosenthal, A. Gringauz, and L. A. Vargas, J.C.S. Chem. Comm., 1976, 384.

84

Tervalent Phosphorus Acids 0

(Me,SiO),PCH,OSiMe,

RCW'

t

ll RCH,PCH,OSiMe,

---

85

0

HO

II

RCH,PCH,OH

I

I

OSiMe,

OH

(7)

hydrolysis, provides a method for introducing the hydroxymethylphosphinate group. The Michaelis-Arbusov alkoxyphosphonium salt intermediate (8) has been isolated from a low-temperaturereaction of 2-chlorotetrahydropyran with trimethyl phosphite and antimony pentachloride.s The corresponding trifluoromethyl sulphonate (9) can be prepared independently by trapping the oxocarbenium ion (10) with trimethyl phosphite (Scheme 1). Mild dealkylation of (8) or (9) with hydroxide

+ (10)

1

y

(11)

+oi.CoMe), CF,S03(9 1

Reagents: i, (Me0)3P-SbC15, -78 "C; ii, OH-; iii, Me30+ SbCL-; iv, CFsS03H; v, (MeO)aP, -78 "C.

Scheme 1

ion provides the phosphonate (1 l), which can be re-converted into (8) by alkylation with trimethyloxonium hexachloroantimonate. A kinetic study of the Arbusov contribution in the reactions of triethyl phosphite and aryl-substituted a-bromoacetophenones gives a Hammett p value of -0.22.6 This suggests that the ketophosphonate product is formed via substitution at carbon and that attack on bromine is unlikely. The reaction of phosphites with trialkyloxonium salts in acetonitrile generally gives the corresponding alkyltrialkoxyphosphonium salt (12). However, under the same conditions, the bicyclic phosphite (13) accepts a proton, rather than an alkyl group, to give (14).' Surprisingly, X-ray diffraction shows (14) to possess a trigonalbipyramidal tricyclic structure with phosphorus co-ordinated to nitrogen. N-

ti

7

J. Thiem, M. Gunther, and H. Paulsen, Chem. Ber., 1975, 108, 2279. E. M. Gaydou and J.-P. Bianchini, J.C.S. Cliem. Comm., 1975, 541. J. C. Clardy, D. S. Milbrath, J. P. Springer, and J. G. Verkade, J. Amer. Chem. SOC.,1976, 98, 624.

4

86

Organoyhosphori~sChemistry

Silylated iminophosphines (15) react with alkyl halides to give the iminophosphoranes (16).8 Similar reactions with Main-group IV and VII halides give the heterocycles (17) via the intermediate 1,2-addition products (1 S), which can be isolated in the case of germanium. Attack on Unsaturated Carbon. The annual addition of phosphites to every variety of activated double bond continues. These include nitro-alkenes, ab-unsaturated The carboxylic acid derivatives,lO maleimides,ll fulvenes,12and pyridinium ~a1ts.l~ reaction of diethyl phosphite with keten 0 , N - ,S,N-, and N,N-acetals has been used to prepare the enamine phosphonates (19).14 The ag-unsaturated thioketone (20) undergoes Michael addition of trimethyl phosphite to give (21), which cyclizes to (22).15A similar addition of benzylalkyl (or

*

E. Niecke and W. Bitter, Chem. Ber., 1976, 109, 415. R. D. Gareev, E. E. Borisova, and I. M. Shermergorn, Zhur. obshchei Khirn., 1975, 45, 944 (Chem. Abs., 1975,83,28 337); E. E. Borisova, R. D. Gareev, T. A. Guseva, and I. M. Shermergorn, ibid., p. 943 (Chem. Abs., 1975,83, 43451). lo A. N. Pudovik, E. S. Batyeva, A. S. Selivanova, V. D. Nesterenko, and V. P. Finnik, Zhur. obshchei Khim., 1975, 45, 1692 (Chem. Abs., 1976, 84, 5064); C.-G. Shin, Y. Yonezawa, Y. Sekine, and J. Yoshimura, Bull. Chem. SOC.Japan, 1975,48, 1321. l1 A. N. Pudovik, E. S. Batyeva, and G. U. Zamaletdinova, Zhur. obshchei Khim., 1975, 45, 940 (Chem. Abs., 1975, 83, 43450); A. N. Pudovik, E. S. Batyeva, Yu. N. Girfanova, and V. Z. Kondranina, Zhur. obshchei Khim., 1975, 45, 2618 (Chem. Abs., 1976, 84, 105689). l2 N. R. Vladimirskaya, V. I. Koshutin, and V. A. Smirnov, Izvest. Sev.-Kavk. Nauchn. Tsentra Vyssh. Shk., Ser. Estestv. h'auk, 1975, 3, 24 (Chem. Abs., 1976, 84, 17505). l3 D. A. Predvoditelev, T. G. Chukbar, and E. E. Nifant'ev, Khim. geterotsikl. Soedinenii, 1975, 377 (Chem. Abs., 1975, 83,43447). l4 M. Fukuda, K. Kan, Y. Okamoto, and H. Sakurai, Bull. Chem. SOC.Japan, 1975, 48, 2103. l5 B. A. Arbusov, N. A. Polezhaeva, and V. V. Smirnov, Izvest. Akad. Nauk S.S.S.R., Ser. ktiim., 1975, 688 (Chem. Abs., 1975, 83,43446).

Tervalent Phosphorlrs Acids 0

R'CH=CR2NMe,

I1 + (EtO),PH

R2 = OMe, SEt, or NMe,

-

0

ll

(El-R'CH=C(NMe,)P(OEt), (19)

S

II MeC--C=CHMe I CO,E t

87

Me

+ (MeO),P

--+

0

II

hkS-- C=CCI-IMeP(OMe), CO,E t

aryl) phosphinites to ag-unsaturated ketones has been used to prepare A2-phospholen 1-oxides (23),le The reaction of 2-phenyl-l,3,2-dioxaphospholan with acrylic acid and acrylamide provides the first synthesis of cyclic acyloxy-(24) and amido-(25) phosphoranes.l7 + CH,=CHCOXH

Ph()

4

P 3

0 (24) X = 0 (25) X = NH

(28) R = Me l7

R. Bodalski, K . M. Pietrusiewics, and J. Koszuk, Tetrahedron, 1975, 31, 1907. T. Saegusa, S. Kobayashi, and Y. Kimura, J.C.S. Chem. Comm., 1976, 443.

Organophosphorus Chemistry

88 Ph p h b O Ph

+

R,P

I

R,P=-C--C=C=O

I

Ph (29)

Further studies of the reactions of secondary and tertiary phosphites with cyclopentadienones have included the keto-cyclone (26), which gives the phosphonates (27) and (28), respectively.18 Ketenphosphoranes (29) have been prepared by the reaction of diphenylcyclopropenone with a variety of tervalent phosphorus compound~.~~ Recently reported additions of dibutyl phosphinite2O and tetra-alkoxydiphosphines21to alkenes are probably of free-radical nature, although the reactions only take place with alkenes possessing electron-withdrawing groups. The usual flood of reports concerning the addition of phosphites to imines has appeared. These include the reaction of hypophosphites to give cc-aminoalkylphosphinic acid salts possessing antibacterial activity22and the synthesis of A4-1,4,2A5-oxazaphospholines(30) from phosphites and carbo~amides.~~ The addition of

Ph (31)

dimethyl phosphite to the Schiff base (31) involves attack on nitrogen rather than carbon, presumably because of the aromatic nature of (32).24 Similar additions to 18

l9 2o

21 22 23

24

A. V. Fuzhenkova, A. P. Zinkovskii, and Yu. I. Khramtsov, Zhur. obshchei Khim., 1976, 46, 285 (Chem. Abs., 1976, 84, 164944). A. Hamada and T. Takizawa, Chem. and Phnrm. Bull. (Japan), 1975, 23, 2933. K. Issleib, W. Kitzrow, and I. F. Lutzenko, Phosphorus, 1975, 5, 281. I. F. Lutsenko, M. V. Proskurnina, and A. L. Chekhun, Zhur. obshchci Khim., 1976, 46, 568 (Chem. Abs., 1976, 84, 180349). V. I. Yudelevich, L. B. Sokolov, B. I. Ionin, and L. G . Myasnikova, Zlzur. obshchei Khim.,1975, 45, 1554 (Chem. Abs., 1976, 84, 44278). J. Albanbauer, K. Burger, E. Burgis, D . Marquarding, L. Schabl, and I. Ugi, Annalen, 1976,36. B. A. Arbusov, E. N. Dianova, A. V. Fuzhenkova, and A. F. Lisin, Izoest. Akad. Nauk S.S.S.R., Ser. khim., 1975, 1825 (Chem. Abs., 1975, 83, 206385).

89

Tervalent Phosphorus Acids

azines give the expected product through attack on carbon,26and this reaction, followed by hydrolysis, has been used to prepare or-aminophosphinic acids.26 Diethyl dl-1-aminobenzylphosphonatehas been prepared by a Mannich reaction of diethyl phosphite, benzaldehyde, and ammonia, resolved as its D-mandelate salt, and hydrolysed to give ( )-1-aminobenzylphosphonic acid.27While the tetraethyldiamide (33) reacts with benzaldehyde to give the expected phosphonic diamide (34), the corresponding tetramethyl-diamide reacts, with migration of the dimethylamino-group, to give (35).2*

+

0

(33) 0

(34)

II

A/OH (Me,N),PH + PhCHO --+ Me,NP, CHPhNMe, (35)

cis-a/?-Dimethoxycarbonylstilbeneoxides have been prepared by the reaction of hexamethylphosphorous triamide with aryl glyo~ylates.~@ Electronic and steric effects should favour the formation of the trans-l,4,2-dioxaphospholan(36), and a concerted (allowed) retrograde ,2s + ,48 cycloaddition of (36) followed by conrotatory cyclization of (37) would give the cis-stilbene. The reactions of phosphites and phosphines with the ketone (38) and thioketone (39) are complex, and tetrathiafulvalenes (a), betaines (41), and phosphonates may be formed, depending on the condition^.^ *

I C0,Me

(36) Ar

Me0,C

C0,Me

CO,Me (37)

27

E. E. Nifant’ev, N. V. Zyk, and M. P. Koroteev, Zhiir. obshchei Khim., 1975, 45, 1455 (Chem. Abs., 1975, 83, 179218). J. Rachon and C. Wasielewski, Roczniki Chem., 1975,49, 397 (Chem. Abs., 1975, 83, 10294); E. E. Nifant’ev, N. V. Zyk, M. P. Koroteev, and V. N. Abramov, Zhur. obshchei Khim., 1975, 45, 2162 (Chem. A h . , 1976, 84, 59657). M. K. Rho and Y . J. Kim, Taehan Hwahak Hoechi, 1975, 19, 434 (Chem. Abs., 1976, 84,

28

E. E. Nifant’ev and I. V. Shilov, Zhur. obshchei Khim., 1975, 45, 1264 (Chem. Abs., 1975, 83,

29

147 546). G. W. Griffin, D. M. Gibson, and K. Ishikawa, J.C.S. Chem. Comm., 1975, 595. M. G. Miles, J . S. Wager, J. D. Wilson, and A. R. Siedle, J. Org. Chem., 1975, 40,2577.

25 26

150 703).

3O

90

Organophosphorus Chemistry

(44) R1 = OAlkyl (45) R’ = Alkyl

The isochromanylphosphonate(42) has been prepared by the reaction of triethyl phosphite with 2-(2’-bromoethyl)ben~aldehyde.~~ A related reaction is the one-step synthesis of phosphomycin derivatives from the base-catalysedreaction of secondary phosphites with or-halogenoketonesreported by Haake.32N.m.r. evidence was obtained for a phosphonate halohydrin intermediate (43).by-Epoxyalkyl-phosphonates (44)and -phosphines (45) have also been prepared from epibrorn~hydrin~~ and from ap-epoxy-ketone~.~~ Several unexceptional examples of the Perkow reaction have been reported, including the reaction of trimethylsilyl dimethyl phosphite with diethyl trichloroacetylphosphonate to give (46)35 and of triethyl phosphite with the halogenomethyl heterocyclic ketones (47) to give mixtures of enol- and ketophosph~nates.~~ Insecticidal enol-phosphonates (48) have been prepared from aryl 31 32 33 34

35 36

€1. Gross and I. Keitel, Tetrahedron Letters, 1976, 915. B. Springs and P. Haake, J. Org. Chem., 1976, 41, 1165. A. P. Rakov, E. A. Kosterin, and G. F. Andreev, Zhur. obshchei Khim., 1975,45, 1760 (Chem. Ahs., 1975, 83, 206381). A. N. Pudovik, M. G. Zimin, and A. A. Sobanov, Zhrir. obshchei Khim., 1975,4§, 1232 (Chern. Abs., 1975, 83, 131 686). I. V. Konovalova, L. A. Burnaeva, and A. N. Pudovik, Zlirw. obshchei Khim., 1975, 45, 2567 (Chem. Abs., 1976, 84,44258). A. Arcoria, S. Fisichella, E. Maccarone, and G. Scarlata, J. Heterocyclic Chem., 1975, 17, 215.

Tervalerit Phosphorits Acids

91 0

0 It

Me,SiOP(OEt), + CI,CCOP(OEt)2

--+-

0

It I/ (EtO)?POC----I”(OEt)2 II CCI, (46)

halogenoalkyl ketones, and the effect of the reaction conditions on their stereochemistry has been thoroughly in~estigated.~’ Surprisingly, the Perkow reaction of chloroacetyl chloride proceeds normally to give the enol-phosphonate (49) as the major product,5*although on the basis of the accepted mechanism for the Perkow reaction, other products should be preferred. The reactions of dimethyl phenylphosphonite with acid chlorides, cc-halogenoketones, and N-(bromomethy1)phthalimide have been used to prepare acyl phosphinates, P-keto-alkylphosphinates, and phthalimidomethylphosphinates as intermediates in the synthesis of a-diazophosphinic a-Amino-phosphonateshave also been prepared by the addition of secondary phosphites to nitriles40 and to i~ocyanides.~~ Attack on Nitrogen. A variety of cyclic derivatives of phosphorous acid have been converted into spirophosphoranes (51), using diethyl azodicarboxylate as the condensing probably by initial addition to nitrogen to give (50). Several 37 38 38 40

*l 42

R. Malinowski and M. Mikelajczyk, Pr. Inst. Przem. Org., 1974, 6, 95 (Clzcm. Abs., 1976, 84, 164 949). 0. E. Nasakin, V. V. Kormachev, and V. A. Kukhtin, Zhur. obshchei Khim., 1975, 45, 2374 (Chem. Abs., 1976, 84, 59668). U. Felcht and M. Regitz, Chem. Ber., 1975, 108, 2040. V. V. Orlovskii and B. A. Vovski, Zhur. obshchei Khim., 1976, 46, 297 (Chem. Abs., 1976, 84, 164 946). A. N. Pudovik, V. I. Nikitina, M. G. Zimin, and N. L. Vostretsova, Zliur. obshckei Khim.,1975, 45, 1450 (Chem. Abs., 1975, 84, 179217). S. A. Bone and S. Trippett, J.C.S. Perkin I , 1976, 156.

92

Organophosphorus Chentistry

Me,SiOP(OMe),

f

PhN,

--+

(MeO),&--N=N-NPh

I

OSiMe,

0

0

II

It (MeO),P-N=N-NI1Ph

,SiMe,

(Me0)2P-N=N--N

( 5 3)

P' h (5 2)

reports have appeared on the reaction of phosphites with azides to give the corresponding phosphite imine~,"~ while the addition of dimethyl trimethylsilyl phosphite to phenyl azide gave (52), which on hydrolysis gave the stable phosphonate (53).44 Attack on Oxygen. Nitrones have been deoxygenated to the parent imine with trimethyl phosphite under vigorous conditions.46Virtually quantitative yields of the enol-phosphates (54) and (55) were obtained from the reaction of tris(trimethylsily1) phosphite with or-diketones and p-benzoq~inone.~~ 0

II

,/P(OSiMe.J,

'

0

II

Me,SiOCR=CROP (OSilfeJ, (54)

*x-

:1

(Me,SiO),P O-+ OSiMe,

(5 5 ) 43 44 45

46

E.g. D. E. Arrington, J.C.S. Dalton, 1975, 1221. R. D. Gareev, Zhur. obshchei Khim., 1975, 45, 2557 (Chem. Abs., 1976, 84, 44257). B. A. Arbusov, E. N. Dianova, V. S. Vinogradova, and A. F. Lisin, Izuest. Akad. Nauk S.S.S.R., Ser. khini., 1975, 695 (Chem. Abs., 1975, 83, 28335).

T. Hata, M. Sekine, and N. Ishikawa, Chern. Letters, 1975, 645.

93

Tervalent Phosphorus Acids

Attack on Halogen. Predictably, the 3-bromo-3-cyano-imides (56) and (57) form quasiphosphoniumsalts (58) with aryl phosphites, phosphonites, and ph~sphinites.~' In the case of (56) these salts cyclize to the oxazaphosphorane (59), which is in equilibrium with the iminophosphorane (a), depending on the phosphorus ester used.

(56) n = 1 (57) n = 2

Br

0 Me

Me

In a continuation of his phosphine-carbon tetrachloride reactions, Appel has reported a convenient synthesis of alkyl phosphinates from chlorophosphines, alcohols, carbon tetrachloride, and base.48The reaction presumably takes place via the alkoxyphosphonium salt (61) and an Arbusov reaction. The reaction of nucleophiles with monoalkoxyphosphonium salts (62), obtained from the reaction of glycols with tris(dimethy1amino)phosphine-carbon tetrachloride, provides a highyield route to monofunctionalized alcohols.49The tris(dimethy1amino)phosphinecarbon tetrachloride reagent converts vicinal diols into trans-epoxides or spirophosphoranes, depending on the diol sub~tituents.~ O The proposed mechanism is shown in Scheme 2, and the relative rates of rotation and y-elimination in the intermediate (63) control the products formed. Secondary phosphites react in a similar way with carbon tetrachloride, and further reaction with trimethyl sulphoxonium ylide gives a high yield of the phosphonylsulphoxonium ylide (64).5l 47

48 49

50

51

M. F. Pommeret-Chasle, A. Foucaud, M. Leduc, and M. Hassairi, Tetrahedron, 1975,31,2775. R. Appel and U. Warning, Chem. Ber., 1976, 109, 805. R. Boigegrain, B. Castro, and C. Selve, Tetrahedron Letters, 1975, 2529. R. Boigegrain and B. Castro, Tetrahedron Letters, 1975, 3459; R. Boigegrain and B. Castro, Tetrahedron, 1976,37, 1283; R. Boigegrain, B. Castro, and B. Gross, Tetrahedron Letters, 1975, 3947. V. P. Lysenko, I. E. Boldesskul, Y. G. Cololobov, and R. A. Loktionova, Zhur. org. Khim., 1975,11, 2440 (Chern. A h . , 1976,84,44283).

94

0rganophosphorus Chemistry

Reagents : i, (Me2N)$CI; ii, Cch-; iii, HO(CH&OH.

Scheme 2 0

II (E t O),PH

0

C(1,

0

II II -+ (EtO),PCH=SMe,

II II

(64)

M e,S =CH,

c1 ClPWMe,),

(651

ArCH Oif

Bt,,,

: ArCII,OP(NMe,),

PhCCI,

*

I

ArCH,O~(NMe,), PhCCI,

(66)

A r C E C P h +-

JArCH,CCl$h

B

+ (Me,N),PCII

A new synthesis of diarylacetylenes in moderate yield has been r e p ~ r t e d The .~~ reaction of a benzyl alcohol with the phosphorochloridite (65) gives the phosphorodiamidite (66), which reacts with benzotrichloride to give a 1,1 -dichlorodibenzyI. Finally, dehydrohalogenation gives an arylphenylacetylene. The phosphoruselimination step probably involves an Arbusov-type reaction, and this suggestion is supported by kinetic data. 31P N.m.r. spectroscopy of the Arbusov reaction of halogens or benzenesulphonyl chloride with cyclic phosphites is said to provide the first direct evidence for a five-co-ordinated intermediate in the reaction.53 52

53

J. H. Hargis and W. D. Alley, J.C.S. Chem. Conzm., 1975, 612. A. Skowroska, J. Mikolajczak, and J. Michalski, J.C.S. Chem. Comm., 1975, 791,

TerualentPhosphorus Acids

95

Electrophilic Reactions.-A high-yield conversion of optically active alcohols into the corresponding halides, using a modified phosphorus trichloride reaction, has been The crucial conditions appear to be a low-temperature (-25 "C)initial reaction, followed by prolonged stirring at 4 "C to allow complete cleavage of the intermediate phosphite esters before distillation. Oxetans undergo ring-opening with

R2 = CHJHMe, CHMeCHMe, or CN,CH,CH, (RO),PCl

Me,SiN

f

--+ (Ro),P-Np~

. b N

(69)

the phosphorous acid bromides (67) to give (68), which isomerize to cyclic phosphonates on heating.55 Phosphorous acid chlorides have been used to prepare phosphorous diester triazolides (69), which are excellent condensing agents for peptide synthesis.5 A number of inorganic ring systems containing phosphorus have been synthesized by the reaction of chlorophosphines with silylated amines. These include disilaphospha(m)diazacyclopentanes (70),5 adamantane analogues (71), and four-, six-, and eight-membered rings containing silicon, nitrogen, and p h o s p h o r u ~A . ~variety ~ of new bicyclic hydrazinebis(phosp1iines)(72) has been prepared by the reaction of 3,6-dichloro-l,2,4,5-tetramethylperhydro-l,2,4,5-tetra-aza-3,6-diphosphorine with Me,Si-%Me,

\

. / RN,

,NR

P Me

Me (71)

(70)

Me Me ,N-N CIP Me Me

N-N Me Me (72) X = RN-NR,RN,O,orS

54

55

57

58

R. 0. Hutchins, D. Masilamani, and C. A. Maryanoff, J. Org. Chem., 1976, 41, 1071. B. A. Arbusov, L. Z. Nikonova, 0. N. Nuretdinova, and N. P. Anoshina, Izoest. Akad. Nacrk S.S.S.R., Ser. khim., 1975, 473 (Chem. Abs., 1975, 83, 10288). H. R. Kricheldorf, M. Fehrle, and J. Kaschig, Angew. Chem. Znternat. E d ? . , 1976, 15, 305. U. Wannagat and H. Autzen, 2.anorg. Chem., 1976, 420, 132; ibid., p. 139. U. Wannagat and H. Autzen, Z . anorg. Chem., 1976,420, 119.

96 Li

I

Me2NNSiMe, + (73)

Me,%,

,N---PC1,

-

Organophosphorus Chemistry

Me,N-N-P

I SiMe,

"NCMe,

(74)

Li I

hydrazines and disila~ines.~~ One of several reports of multiply bonded tervalent phosphorus concerns the first synthesis of a phosphatetrazene (74) by the reaction of the lithiated hydrazine (73) with NN-(t-butyltrimethylsilyl)aminodichlorophosphine.60Attempts to prepare the isomer (75) by an analogous method gave only the dimer, presumably due to the lack of the steric effects present in (74). The formation of phosphanylium salts (77) in the reaction of phosphorus trichloride with methylhydrazones, presumably uia the intermediate chlorophosphine (76), may be assisted by aromatic stabilization of the product.g1

J

L (76)

Orthophosphoric and benzylphosphonic acids have been selectively alkylated with triethyl phosphite in a new synthesis of mono-, di-, and triethyl phosphates and of mono- and di-methyl phosphonates.62 N-Methylol carboxamides and sulphonamides react with trialkyl phosphites to give the phosphonate derivatives (78) and (80), respecti~ely.~~ However, the mechanism appears to be quite different in each case; while the carboamides react by a transesterification-rearrangement pathway, the sulphonamides undergo elimination-addition via the imine (79). 59 60

61 62

63

H. Noth and R. Ullmann, Chem. Ber., 1976,109, 1942. 0. J. Scherer and W. Glaebel, Angew. Chem. Znternat. Edn., 1975, 14, 629. J. Luber and A. Schmidpeter, Angew. Chem. Znternat. Edn., 1976, 15, 1 1 1 . A. Markowska, J. Olejnik, and J. Michalski, Chem. Ber., 1975, 108, 2589. D. J. Scharf, J. Org. Chem., 1976, 41, 28.

Tervalent Phosphorirs Acids R'CONHCH,OH 4-

(R20),P

-

97 0

R'CONHCH,OP(ORz), + W'OH

--+

II

R'CONHCH,P(ORZ), (7 8)

R'SO,NHCH,OH

__f

+ R'OH

[R'SO,N=-CH,1 (79)

0

p ) , P

I/

R'SO,NHCH, P(OR2),

t

R'SO,NCH,~(ORz),

(80)

The phosphoranes (81),64 (82),65 and (83),6a each containing a hydrogen ligand, have been prepared by the now standard procedure from amino-phosphines and amino-alcohols.A similar reaction of the amino-alcohol (84) gave oxazaphospholidine derivatives (85).s7 R R'P(NR:), + (HOCHK3CH,)2NH

3 H y \R' f

y

+

uNHz (81)

PhP(NMe,), +

MeCN

OH

H

€1

(82)

-

ArNHCH,CH,OH + PhPX, x = NMe, or c1 (84)

php, (85)

Rearrangements.-Vinyl phosphites (86) undergo catalysed thermal rearrangement to the corresponding phosphonites (87).68 64 65

67 68

D. Houalla, T. Mouheich, M. Sanchez, and R. Wolf, Phosphorus, 1975, 5, 229. C. Malavaud and J. Barrans, Tetrahedron Letters, 1975, 3077. S. A. Terent'eva, M.A. Pudovik, A. N. Pudovik, and Kh. E. Kharlampidi, Zhur. obshchei Khim., 1975, 45, 2559 (Chem. Abs., 1976, 84, 59673). T. T. Dustmukhamedov, M. M. Yusupov, N. K. Rozhkova, and S. R. Tulyaganov, Zhur. obshchei Khim., 1976, 46, 300 (Chem. Abs., 1976, 84, 164947). 2. S. Novikova, S. N. Zdorova, S. Ya. Skorobogatova, and I. F. Lutsenko, Zhur. obshchei Khirn., 1975, 45, 2384 (Chem. Abs., 1976, 84, 74361).

0rganophosp horirs Chemisfry

98

Cyclic Esters of Phosphorous Acid.-A large number of 2-substituted-4-methyl-1,3,2dioxaphospholans (88) have been prepared and their stereochemistry and conformations investigated by lH and 31Pr ~ . m . r .Unlike ~~ the corresponding 1,3dioxans, the trans-isomer (88a) is favoured in all cases, and each isomer is best described in terms of two rapidly equilibrating half-chair conformers with the 4-alkyl group pseudo-axial or pseudo-equatorial. H

Hudson and Verkade have offered an explanation for the conformational preference of phosphorus substituents in both dioxaphosphorinans (89) and their oxides (90).'O In the case of (89) the interactions involved are oxygen-phosphorus lone-pair repulsion, oxygen lone-pair repulsion of electrons in the P-X bond, and a hyperconjugative attraction involving the antibonding orbital of the P-X bond. In some cases, interactions with lone pairs of electrons on the phosphorus substituent also contribute. The variable conformational preference of amino-groups in 1,3,2dioxaphosphorins has been investigated by Stec and his co-workers. While tb~tylarnino-~l and anilino-groups72 are largely axial at equilibrium, the dimethyl-

C1

PhNH 10

90

a

I

Ph NH

(92) O9

7* 7l 72

W. G . Bentrude and H. W. Tan, J. Amer. Cheni. SOC., 1976, 98, 1850. R. F. Hudson and J. G . Verkade, Tetrahedron Letters, 1975, 3231. T. J. Bartczak, A. Christensen, R. Kinas, and W. J. Stec, Tetrahedron Letters, 1975, 3243. W. J. Stec and A. Okruszek, J.C.S. Perkin I , 1975, 1828.

TerunEent Phosphorus Acids

99

I

c1 amino-group72 prefers the equatorial orientation. The results are attributed to varying steric effects. The stereochemistry of (91), prepared from 2-chloro-4-methyl1,3,2-dioxaphosphorin(92), was determined by stereospecific oxidation to the correA similar reaction sponding 2-oxides, the stereochemistry of which is with t-butylamine gave a mixture (26:74 by 31P and 13C n.m.r.) of cis- and trans-2-t-butylamino-4-methyl-1,3,2-dioxaphosphorin (93) which did not change on distillation. Treatment of this mixture with selenium gave the corresponding cis- and trans-selenides (30 :70 by n.m.r.).?l The stereochemistry of the seven-membered cyclic phosphites (94),(99, and (96), prepared from the base-catalysed reaction of triphenyl phosphite and the correThe results suggest sponding diol, has been investigated by lH, 13C,and 31Pr~.m.r.?~ that each of the three heterocycles adopts a different conformation in solution.

Miscellaneous Reactions.-A full report has appeared of the reactions of carbon dioxide and carbon disulphide with tervalent phosphorus aryl esters and amines; the products are ureas and thioureas, respectively.'* The suggested mechanism, previously invoked for similar reactions of carboxylic acids, involves the N-phosphonium salt (97). 0

II

(PhO),PH

+

PfiNH,

+

-

PhNHCONHPh

I I1 H-P-X-C-NHPh

PhNH,

+

PhOH

/o

+

PhOP-H

-0"oPh (97)

I

OH

2,3,4,5-Tetraphenylcyclopent-3-enoneand dimethyl phosphonate are the major products from the base-catalysed reaction of methyl phosphonate with tetracyclone.75 A mechanism involving initial hydride transfer from dimethyl phosphinate anion to the ketone followed by kinetically controlled protonation to give (98) is suggested. 73 74

75

A. C. Guimaraes and J. B. Robert, Tetrahedron Letters, 1976, 473. N. Yamazaki, I. Iguchi, and F. Higashi, Tetrahedron, 1975, 31, 3031. C. J. R. Fookes and M. J. Gallagher, J.C.S. Perkin I, 1975, 1876.

Organophosphorus Chemistry

100 [MeO%]-

+ H

\ MeOP-0

0

+

An unusual rearrangement with elimination of acetonitrile to give (100) occurs on heating the silylated amide (99).7s

(RO),P-N

/

\

SiMe,

COMe

-

(RO),P -0-SiMe, (100)

(99)

The dimer (101) is slowly formed from bis(trimethylsilyl)aminotrimethylsilyliminophosphine on standing at room temperature. The stereochemistry of (101) appears to be fixed, due to a very high (AG;, > 27 kcal mol-l) P-N rotational barrier. 3 Phosphonous and Phosphinous Acids and their Derivatives Gallagher has reported a convenient synthesis of functionalized phosphorinans (102) by Michael addition of methyl hypophosphite to methyl acrylate, followed by baseinduced cyclization.7 8 The secondary phosphine oxide (104) has been reported as an intermediate in the reaction of benzylbis(cc-hydroxybenzy1)phosphine oxide (103) with amines to give (105).7DThe same authors now report the results of direct reaction of (103) with imines * O to give (105) and the reaction of (103) with aldehydes to give acetals (106). M. A. Pudovik, L. K. Kibardina, T. A. Pestova, and M. D. Medvedeva, Zhur. obshchei Khim., 1975,45,2568 (Chem. Abs., 1976, 84,44259). W. Niecke, W. Flick, and S. Pohl, Angew. Chem. Internat. Edn., 1976, 15, 309. 78 M. J. Gallagher and J. Sussman, Phosphorus, 1975, 5, 91. 7 9 A. B. Pepperman and T. H. Siddall, J . Org. Chem., 1975,40, 1373. so A. B. Pepperman and T. H. Siddall, J. Org. Chem., 1975, 40, 2053. A. B. Pepperman, T. H. Siddall, and G . J. Boudreaux, J. Qrg. Chem., 1975, 40, 2056; S. A. Buckler, J. Arner. Chem. SOC.,1960, 80, 4215. 76

77

Tervalent Phosphorus Acids

-

0

11 MeOPH,

+ CH,=CHCO,Me

101 0

It

MeOPCH,CH,CO,Me H lCH,=

C0,Me

r(

0

II PhCH,P(CHOHPh),

CHC0,Me

0

II

+-

-

MeOP(CH,CH,CO,Me),

0

IIH,

PhCH P ’ ‘CH(0H)Ph

CHPhNHR I I/ PhCH P

’ ‘CHOHPh

+ PhCHO

PhCH-NR

In the presence of two moles of reagent, the oxide (103) can act as a source of primary phosphine oxide through loss of both hydroxybenzyl groups.

B u‘,

Optically active phenyl-t-butylphosphine oxide with the same sign of rotation has been prepared by the reaction of Raney nickel with the (+)-selenide (107) and the (+)-sulphide which suggests that the latter compounds have the same sign of rotation for the same absolute configuration. The absolute configuration of (-)phenyl-t-butylphosphine oxide was apparently established by conversion into ( - )methylphenyl-t-butylphosphineoxide, but no details have been given. 82

J. Michalski and Z. Skrzypzynski, J. Organometallic Chem., 1975, 97, C31.

6 Quinquevalent Phosphorus Acids ~

~~

BY R. S . EDMUNDSON

An increase in the output of papers dealing with derivatives of phosphoric, phosphonic, and phosphinic acids during the period under review has required even greater selectivity in the final choice to be included here; about half the published papers are not covered by the present Report. Marked activity has been evident in the general areas of phosphorylation and assignment of configuration in phosphoruscontaining ring systems, but application of these ring compounds to the study of mechanisms of reactions at phosphorus, and in the synthesis of chiral phosphorus compounds, continues to be of particular interest. The final volume of ‘OrganophosphorusCompounds’, edited by Kosolapoff and Maier, contains chapters on phosphonic acids and their derivativesla and organic derivatives of thio- (seleno-, telluro-)phosphoricacids.lb The stereochemistry of optically active phosphorus thio-acids has been reviewed and published lectures have covered such topics as phosphate and phosphonate compounds based on adamantaneS and NN-dihalogeno-amides of phosphoric acids.4

1 Synthetic Methods General.-Triethyl phosphite has been used to achieve stepwise 0-ethylation of phosphoric and benzylphosphonic acids.5 The disulphide linkage in bis(phosphiny1) disulphides is cleaved by ammonia in a suitable solvent to yield the phosphinylsulphenamides (1).

The reaction between phosphorus dichlorides and a-hydroxyiminocarboxylic acids

6

‘OrganophosphorusCompounds’, ed. G. M. Kosolapoff and L. Maier, Wiley, New York, 1976, Vol. 7, (a) Chapter 18, by K. H. Worms and M. Schmidt-Dunker, (b) Chapter 19, by D. E. Ailman and R. J. Magee. M. Mikolajczyk and M. Leitloff, Rum. Chem. Rev., 1975, 44, 670. E. S. Shepeleava, D. M. Oleinik, E. I. Bagri, and P.I. Sanin, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 5th, 1972 (publ. 1974), p. 369 (Chem. A h . , 1975, 83, 147524). A. M. Pinchuk, L. N. Markovskii, T. V. Kovalevskaya, G . S. Fedyuk, T. N. Dubinina, S. I. Zhila, and A. V. Kirsanov, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 5th, 1972, (publ. 1974), p. 51 (Chem. Abs., 1975, 83, 114514). A. Markowska, J. Olejnik, and J. Michalski, Chem. Ber., 1975, 108, 2589. U.S.S.R. P. 483401/1975 (Chem. A h . , 1976, 84, 59738).

102

Qrriiiquevalent Phosphorus Acids

103

or esters yields 1,3,2-0xazaphospholines(2) (see also ref. 49).' Stereoselectivity in the formation of 1,3,2-0xazaphospholidines from phosphorus dichlorides and propanolamines is evidently dependent upon the substituent on nitrogen : a mixture of diastereoisomers of (3) results when R1 = Me but homogeneous isomers are obtained when R1 = Ph.8 ,OR'

Me,,OII

The optically active thiones (4), readily obtainable from ( - )-ephedrine, undergo P-N bond fission, with inversion of configuration at phosphorus, when treated with ethanolic HCl ;this provides a highly recommendable method for the preparation of valuable amounts of optically active acyclic compounds (9,isolable as the S-methyl esters (6).9

E tOII- HCI I'

E'

R"

\

OEt

'H (4)

(6)

not isolated (5)

R*is =S; R2 = Me, or O-alkyl and compounds epimeric at P New, stereospecific syntheses of (+)-(R)- and (-)-(S)-ethyl isopropyl methyl phosphate, (+ )-(R)-0-ethyl 0,s-dimethyl phosphorothioate, and (+)-(R)-ethyl Me

/I$*

0

Em-.

EtO,,

,,Me

MeOIT-IICI

~

c

Me0

0//P\MeNK'

Eta--, ,Me 'P Me0/ \o

Me0 I OMe

(7) 7

U.S.S.R.P. 498313/1976 (Chem. Abs., 1976, 84, 105766).

8

M. A. Pudovik, M. D. Medvedeva, and A. N. Pudovik, Zhur. obshchei Khim., 1975,45, 1390 (Chem. Abs., 1975,83, 131 691). D. B. Cooper, C. R. Hall, and T. D. Inch, J.C.S. Chem. Comm., 1975, 721.

104

Organophosphorus Chemistry

K

R2,R3 = Pri, Et

R1 =

R20, ,OR' "P OH ' h e i ; H,O-H+ ii; MeI(X = S , Rz = PI', R3 = Et)

Me0 OMe

methyl methylphosphonate, starting from the bicyclic compounds (7) and (8) based on D-glucopyranose, have been described.1° Ring opening of the N-methylated 1,3,2-0xaza- and 1,3,2-diaza-phospholidine rings with phosphoric and phosphonic acids yields 2-aminoethyl derivatives of pyrophosphoric and pyrophosphonic acids (9) ; 2-dimethylamino-l,3,2-dioxa-

(9)

X = 0 ox NMe; R = PhO or PI1

phospholans and acyclic dimethylamino-compounds, on the other hand, appear to react very slowly in this manner.ll The interaction of 1,2-dicarbonylcompounds and dihydrazides in 1:1 ratio yields 3,4-dihydro-2H-1,2,4,5,3-tetra-azaphosphepine 3-sulphides (10).l2

R'P(S)(NHNH,),

R?COCORZI (10 )

Phosphoric Acid and its Derivatives.-Triacetyl phosphate l3 and diammonium monoacetyl phosphate14have been obtained by acetylation of phosphoric acid with keten at - 10 to - 15 "Cin diethyl ether and ethyl acetate, respectively; the reaction can be controlled to give 90% yields of either product. Long-chain monoalkyl C. R. Hall, T. D. Inch, G. J. Lewis, and R. A. Chittenden, J.C.S. Chem. Comm., 1975, 720. P. Chabrier and Nguyen Thanh Thuong, Comp -.,rend., 1975, 281, C, 397. l 2 A. F. Grapov, 0. B. Mikhailova, and N. N. Mel'nikov, Zhur. obshchei Khim., 1975, 45, 1392 (Chem. Abs., 1975,83, 131692). l3 A. Ungureanu and C. Liteanu, Rev. Roumaine Chim., 1975,20,721 (Chem. Abs., 1975,83,96367). l4 G. M. Whitesides, M. Siegel, and P. Garrett, J. Org. Chem., 1975, 40, 2516. lo

l1

Quiriquevalent Phosphorus Acids

105

phosphates are obtainable by direct reaction between the alcohol and phosphoric acid at temperatures below 130 "C; at higher temperatures the dehydration of the alcohol becomes more important.ls The phosphoramidic chloride (11) has been employed to phosphorylate phenols and alcohols, including carbohydrates.ls Other activity in phosphorylation chemistry has been mostly concentrated in two main areas. In the first of these, Japanese workers have continued their studies on the use of 2-substituted-4-nitrophenylphosphoric acids. The N-protonated form of the 2-dimethylamino-compound (1 2 ; R = Me) is a better phosphorylating agent than the corresponding 2-diethylaminocompound. The reaction of (12) with hydroxy-amines results in selective O-phos-

phorylation, and with hydroxythiols the S-hydroxyalkyl phosphorothioate is the main product.17Primary hydroxy-groups are selectivelyphosphorylated by the same compounds.ls The pyridinium phenyl phosphate (13) phosphorylates alcohols in pyridine in the presence of triethylamine, but inorganic polyphosphates are formed in the absence of the latter.l* In the second area of interest, the high reactivity of compounds that stems from inherent ring strain in fivemembered ring systems has been exploited in the synthesis of mixed diesters of phosphoric acid. These, for example (15), may be obtained by

cleavage of the corresponding 2-hydroxyphenyl triesters (in turn obtainable from cyclic catechol esters) by lead tetra-acetate or by hydrogenolysis.20Hydrolysis of the benzoxazaphospholines (16; R = alkyl), obtained by transesterification between the corresponding phenoxy-compound and ROH, gives the phosphoramidic acids shown.a1 W. Jasinski and S. Ropuszynski,Przemysl. Chem., 1975,54509 (Chem. Abs., 1975,83,177763). W. S. Zelinski and Z. Lesnikowski, Synthesis, 1976, 185. Y. Taguchi and Y. Mushika, J. Org. Chem., 1975, 40, 2310. la Y. Taguchi and Y. Mushika, Chem. and Pharm. Bull. (Japan), 1975, 23, 1586. l9 Y. Taguchi, Y. Mushika, and N. Yoneda, Bull. Chem. SOC.Japan, 1975,48, 1524. 1o J. Calderon and J. A. Medrano, Anales de Quim., 1975,71,618 (Chem. Abs., 1975,83,178208). 21 T. Koizumi, Y. Yoshida, Y. Watanate, and E. Yoshii, Chem. and Pharm. Bull. (Japan), 1975, l5

l6 l7

23, 1381.

Organophosphoriw Chemistry

106

/

OR OH

H

Ramirez et al. have successfully employed 4,5-dimethyl-1,3,2-dioxaphospholen compounds in their work, summarized in Scheme 1.22 The key intermediate is the

HOCH,

P P OH

o ---P(O) AH

011

"j 0€1

(25) Reagents: i, R1OH-collidine; ii, RCOH; iii, imidazole; iv, dry HCl; v, RZOH-EtsN; vi, COClz; vii, pyridine (R1= Me); viii, MeCN-aq. NazCOs

Scheme 1 22

F. Ramirez and J. F. Marecek, J. Org. Chem., 1975,49,2849; F. Ramirez, J. F. Marecek, and I. Ugi, J. Amer. Chem. SOC.,1975,97, 3809; F. Ramirez, J. F. Marecek, and H. Okazaki, ibid., p. 7181; F. Ramirez, J. F. Marecek, and I. Ugi, Synthesis, 1975, 99; F. Ramirez, H. Okazaki, and J. F. Marecek, ibid., p. 637.

Quinquevalent Phosphorus Acids

107

cyclic R1ester (20), which has normally been obtained by careful hydrolysis of the adduct from biacetyl and the ester (R10)3P,although a better method of preparation of (20) from the same adduct is now available (see ‘Organophosphorus Chemistry’, Vol. 7, p. 106). The same intermediate may be obtained directly from the pyrophosphate (17) and RlOH, or indirectly from the imidazolide (18) or the phosphorochloridate (19). Treatment of (20) with the alcohol R20Hyields the acyclic ester (21), a reaction apparently catalysed by Et,N for primary alcohols but not so for secondary alcohols. Hydrolysis of (21) then yields the desired diester (22). In spite of the ability of all the compounds (17)-(20) to react with primary, secondary, and tertiary alcohols, some selectivity can be achieved. Thus, (17) will phosphorylate (23) and the resultant ester (20) will then react preferentially with the primary hydroxy-group of (24) to give (25). Compound (19) is useful for the phosphorylation of sensitive and (or) poorly nucleophilic alcohols. A new and reliable procedure for the synthesis of 0,s-dialkyl hydrogen phosphorothioates (27) involves the trifluoroacetolysis of the t-butyl esters (26); the method is facilitated by the lack of need to isolate (26).23

The preparation of phosphoramidates from dialkyl phosphites, using the ToddAtherton procedure, has been carried out in two-phase systems containing a phasetransfer agent, for example benzyltriethylammoniumchloride, at 5 mole % concentrati~n.~~ The reaction between dialkyl phosphorocyanatidite and acyl cyanides in dichloromethane at 0 “C parallels that between the same phosphite and 1,Zdicarbonyl compounds, and is probably initiated by attack of tervalent phosphorus on the carbonyl group; the formation of 0-and N-alkyl products, (30) and (29), is an indication of the probable nature (28) of an intermediate.26The extension of the reaction (see ‘Organophosphorus Chemistry’, Vol. 7, pp. 108, 126) to include ethyl phosphorodicyanatidite and 1-keto-estersprovides a route to the 5-phosphabicyclo[3,2,0]heptanes(31) in high yields.28 The reaction between benzoylhydrazineand ethyl or phenyl phosphorodichloridate 5-(2-benzoylhydrazino)-5,6-dihydro-2,8-diphenyl-4~1,3,4,6,7,5-0xatetrayields azaphosphocine 5-oxide (32).27

23 24 25 26

27

A. Zwierzak, Synthesis, 1975, 270. A. Zwierzak, Synthesis, 1975, 507. I. V. Konovalova, L. A. Burnaeva, G. S. Temnikova, and A. N. Pudovik, Zhur. obshchei Khim., 1975, 45, 1003 (Chem. Abs., 1975, 83, 58123). I. V. Konovalova, L. A. Burnaeva, and A. N. Pudovik, Zhur. obshchei Khim., 1975,45, 2558 (Chem. Abs., 1976, 84, 59322). A. F. Grapov, 0. B. Mikailova, and N. N. Mel’nikov, Zhur. obshchei Khim., 1975, 45, 2570 (Chem. Abs., 1976, 84, 59419).

108

Organophosphorus Chemistry 0

I1

R20-PHN

Rz

Me R’ = CN

MeCoR’

(29) ~

4-

m P N C O

Me

CN

R’OP(NCO),

Dialkyl phosphoramidates react with sulphonyl di-isocyanate to give the phosphorylated thiatriazine dioxide derivatives (33),a8 while TMPT and formaldehyde together afford 1,5-dioxo-2,4,6,8,9,11-hexakis(methylamino)-1,5-diphosphabicyclo[3,3,3Jundecane(34) .2

New derivatives and analogues of cyclophosphamide (35; R = H) have been reported so and the diastereoisomeric N-1-phenylethyl derivatives (35 ;

2* 29

3”

Z. Arnold and B. Fiszer, Roczniki Chem., 1975,49, 285 (Chem. Abs., 1975,83, 79203). U.S. P. 3925467/1975 (Chenz. A h . , 1976, 84, 105671). P. B. Farmer and P. J. Cox, J. Medicin. Chem., 1975, 18, 1106.

Quinqiieualent Phosphorus Acids

109

R = PhCHMe) have been prepared and distinguished by n.m.r. spectroscopy.31 Attempts to prepare N-aryl derivatives of cyclophosphamide by cyclization of the phosphoramides (36) proved unsuccessfu1.32 Although this type of reaction has proved to be of great value in the preparation of perhydro-l,3,2-oxazaphosphorines and 1,3,2-oxazaphospholidines when NaOEt, NaOH, or NaH are employed as reagent, in this instance the bis(chloroethy1)amide side-chain presents a further possible reaction site. However, steric effects, also considered as an explanation for instances of failure of the reaction (see ‘Organophosphorus Chemistry’, Vol. 7, p. 111) may be operating adversely. Phosphonic and Phosphinic Acids and their Derivatives.-Further fundamental information on important reactions for preparing phosphonic acid derivatives has

(37)

appeared. The formation of 2,4-dimethyl-l,3,2-dioxaphosphorinan 2-oxide (38) from the sodium salt of the cyclic hydrogen phosphonate (37)and Me1 proceeds stereospecifically, with preservation of configuration of the starting material.33 A recent Russian report discloses that oxidative chlorophosphonation of saturated hydrocarbons may be initiated by hydroperoxides present in the hydrocarb~n.~* Some doubts regarding the relative importance of compounds (39)and (41) uis a uis the carbocation (40) in the phosphorylation of terminal alkenes by PCl, have been resolved, at least partially. Although compounds of types (39) and (41) (after treatRCHClC&P(O)CL, --+ [R6HCH2P(0)CI,] (39)

(40)

--+ RCH=CHP(O)CJ

(41)

ment of the intermediate RCH2CH2k13PCI,complex with SO,) are very often found together as products of this reaction (although there may be a distinct bias towards one or the other), it has not been determined whether (39) and (41) are formed independently or whether (41) is produced via (40)from (39). The rate of phosphorylation appears to be controlled to some extent by the ability of R to conjugate. Electron release by R (R = aryl, alkoxy, or aryloxy) increases the stability of (40)and thus favours the formation of (41).When R = alkyl, elimination of a proton is aided by electron withdrawal by P=O. The initially formed complex RCHClCH2hC13PC&, produced by competing chlorination, must lose HCl more readily than (39), so that (39), which is stable at room temperature, may correspond to (40),that is unstable under the same condition^.^^ 31 32 33 34 35

G. Zon, Tetrahedron Letters, 1975, 3139; R. Kinas, K. Pankiewicz, and W. Stec, Bull. ,4cad. polon. Sci., Skr. Sci. chim., 1975, 23, 981 (Chem. Abs., 1976, 84, 180177). H. Hamacher, Arch. Pharm., 1975, 308, 290. K. Lesiak, B. Uznanski, and W. Stec, Phosphorus, 1975, 6 , 65. T. M. Mal’kovskaya and N. M. Lebedeva, Nefepererab. Nefekhim. (Kazan), 1974, 2 , 42 (Chem. Abs., 1976, 84, 150039). V. G. Rozinov, V. V. Rybkina, E. F. Grechkin, and A. V. Kalabina, Zhur. obshchei Khim., 1975, 45, 1643 (Chem. Abs., 1975, 83, 113490), 1644 (Chern. Abs., 1975, 83, 205443).

110

Organophosphorirs Chemistry

PCI, (followed by SOz) converts ethyl thioethers into alkylthiovinylphosphonic dichlorides (42) 36 and acetals into alkoxy(ary1oxy)vinylphosphonic dichlorides (43).37With the same reagents, t-butyl alcohol yields the phosphonic dichloride (44).3*

Me2CClCH, P(0) cl,

RXCH=CHP(O)Cl,

X =S

(42)

x

(43)

(44).

= 0

Other phosphonic dichlorides (43, (46) have been obtained from phosphorodichloridites and chlorinated dimethyl MeOCHClP(0) Cl,

C1,CHOMe

(ClCH,),O

ROW2

f

*

C I C ~ O c ~ P (cl, 0) (46)

(45)

The reaction between phenylphosphonic dichloride and 2-naphthol in the presence of pyridine to give, ultimately, 2-naphthyl phenylphosphonic acid has been shown to be usefully influenced when DMF is added before the naphthoL40 Amongst the reported syntheses of phosphonic esters, one of cyclohexylphosphonic esters depends on treatment of cyclohexanthione with trialkyl phosphites followed by desulphurization of the intermediate esters (47) with Raney nickel.4L

os

(RO),P_

~

~

~

(

o

R Raney )Nip 2

0; (OR)'

(47)

Improved yields of epoxyphosphonates of type (48) are reported for a developmentof existing synthetic methods, involvingmixing of stoicheiometric amounts of hydrogen phosphonate, m-halogeno-ketone, and a l k ~ x i d e . ~ ~ Bicyclic compounds possessing fused 1,3,2-0xathiaphospholan and tetrahydrothiophen rings are obtainable by reaction between a suitable halohydrin (49) and the anhydride (50), followed by cyclization of the intermediate (51) to give (52).43

37 38 39 40

41 42

43

K. A. Petrov, M. A. Raksha, and Le Dong Khai, Zhur. obshchei Khim., 1975,45, 1503 (Chem. Abs., 1975, 83, 164302). V. V. Moskva, T. Sh. Sitdikova, A. I. Razumov, T. V. Zykova, R. A. Salakhutdinov, and G. F. Namanova, Zhur. obshchei Khim., 1975,45, 1494 (Chem. Abs., 1975,83, 179222). L. Maier, Phosphorus, 1975, 5, 223. T. F. Kozlova, A. F. Grapov, and N. N. Mel'nikov, Zhur. obshchei Khim., 1975, 45, 1392 (Chem. Abs., 1975, 83, 114 562). W. R. Purdum, K. D. Berlin, S. Kelly, and L. G. Butler, J. Org. Chem., 1976, 41, 1 1 60. 2. Yoshida, S. Yoneda, andT. Kawase, Chem. Letters, 1975,279 (Chem. Abs., 1975,83, 10284). B. Springs and P. Haake, J. Org. Chem., 1976, 41, 1165. 0. N. Grishina, L. A. Mukhamedova, N. A. Andreev, and M . A. Nechaeva, Zhur. obshchei Khim., 1975, 45, 731 (Chem. Abs., 1975, 83, 58943).

111

Quiriquevalent Phosphorus Acids S

€IS

II

(49)

A convenient synthesis of ‘half-derivatives’of thiophosphonic acids starts from the corresponding phosphonic dichloride, with isolation of the trimeric thiophosphonic anhydride (53)44a and subsequent reaction of this with amines and alcohol~.~~b S

Treatment of diphenacylphosphinic acid with P,O, in hot toluene leads to 4-hydroxy-2,G-diphenyl-4H-1,4-oxaphosphorin 4-oxide (54) rather than to the phosphinic acid anhydride.45 0

ll

O = P /OYP 70)

Ph (PhCOCH,),P(O) OH

Y*O,\

/-=-7PO,H

Q

0

P-0

Ph

0

w (54)

)P=O

II

(55)

The full dehydration of methylenediphosphonic acid by DCC yields the cage compound (55).46 A useful review of the chemistry of a-aminophosphonicacids has been published.47 Treatment of a-aminomethylphosphonic mono-esters with bromoacetyl halides 44 45

46 47

(a)0. N. Grishina, N. A. Andreev, and E. E. Sidorova, Zliur. obshchei Khiin., 1975, 45, 2344 (Chem. Abs., 1976, 84, 59662); (b) L. Maier, Phosphorus, 1975, 5, 253. L. S. Moskalevskaya and G . K. Fedorova, Zhur. obshchei Khim., 1975,45, 950 (Chem. Abs.,

1975, 83, 43454). T. Glonek, J. R. van Wazer, and T. C. Myers, Inorg. Chem., 1975, 14, 1597. K. Prajar and J. Rachon, Z . Chem., 1975, 15, 209.

112

Organophosphorus Chemistry

yields perhydro-l,4,2-oxazaphosphorin-5-ones(56).48 2-0xo-5,6-dihydro-1,3,2oxazaphosphorines (57) have been prepared as indicated.49

HOC,H,C

P"

RO

CN),<'

MeP(O)C'I,

0

R

(57)

Me

= MeorBu

A synthesis of N-substituted a-aminobenzylphosphinic acids starts from ammonium hypophosphite; this is allowed to react with primary amines together with aldehydes or ketones in the presence of HCl.50 The nature of the products and general success of the Atherton-Todd reaction for the preparation of dialkyl- and diaryl-phosphinic amides from secondary phosphine oxides depends on the order in which reactants are mixed and on the choice of polyhalogen reactant.51 Alkyl(ary1)phosphonites react with NN'-disubstituted ureas and thioureas in the presence of aldehydes to give 1,2,4-diazaphospholidines(58) ; these compounds

(R'O),PRz

+ (MeNH),CX +

R3CH0 --+

p'

M""-/

\R2

R3

X = OorS

x

x

Me

FN\ //

( 5 8)

--+

o

I ll MeNHCNCHR3PI

lRZ

Me

- \

'OH

(59)

undergo ring opening under aqueous conditions with the formation of ureidomethylphosphinic acids (59).52 When acted upon by phosphorous acid, the polymethylenediamides(60) afford the novel diphosphonic acids (61),53while lactams are converted into the related compounds (63).54 The pyrrolidonebis(phosphonic acid) (62) is evidently obtained by ring contraction of the acid (61; y1 = 2).55 48

49 50

U.S.S.R. P. 480713/75 (Chem. Abs., 1975, 83, 19351 1). V. E. Shishkin, Yu. M. Yukhno, B. I. No, and Yu. D. Glinskii, Zhur. obshchei Khim., 1975,45, 2554 (Chem. Abs., 1976, 84, 59672). V. I. Yudelevich and L. B. Sokolov, Zhur. obshchei Khim., 1975,45, 1646 (Chem. Abs., 1975,83,

179 224). E. A. Err and F. I. Kharrasova, Zhirr. obshchei Khim., 1975, 45, 1480 (Chem. Abs., 1975, 83, 179 220). 5 2 U.S. P. 3904654175 (Chem. Abs., 1976, 84, 44349). 5 3 Ger. Offen. 2343 195/75 (Chem. Abs., 1975, 83, 28 372). s4 Ger. Offen. 2343 196/75 (Chem. Abs., 1975, 83, 28371). 5 5 Ger. Offen. 2343147175 (Chcm. Abs., 1975, 83, 28370). 51

Quinquevalent Phosphorus Acids

113

1,3,2,5-0xazadiphospholidines(64) are obtainable from a-aminomethylphosphonic esters as i n d i ~ a t e d . ~ ~

(R‘O), P(0) CH, NHR’

R3 N , 7 / O RiNPCl, + RZNP, ,P O

‘OR

The NN’An example of the diazaphosphoridinering system has been di-t-butyl phosphonic diamide (65), prepared conventionally, is treated with t-butyl hypochlorite to give the mono-N-chloro-derivative(66), which readily loses HCI to give lY3,2-tri-t-butyldiazaphosphoridine 3-oxide (67), which can be isolated by sublimation. Methanolysis of (66) at 100 “C yields the phosphonic hydrazide (68).

(66)

R = But

The initial observations, reported in 1972, on the ring expansions to azaphosphepines which take place when A3-phospholen l-oxides are treated with one molar proportion of each of butyl-lithium and a nitrile have now been extended. The use of two molar proportions of each of butyl-lithium and nitrile results in a further twoatom ring enlargement to give the 1,3,2-diazaphosphacyclonona-4,6,8-trienes (69), albeit in only 3-5 % yields. Alkylation at nitrogen takes place when (69) are treated with NaH and alkyl halides.58 56 57

58

Zh. M. Ivanova, E. A. Suvalova, and Yu. G. Gololobov, Zhnr. obslzchei Kliim., 1975, 45, 949 (Chem. Abs., 1975, 83,43453). H. Quast, M. Heuschmann, and M. 0. Abdel-Rahman, Angew. Chem., 1975, 87,487. J. P. Lampin, H. Laurent, and F. Mathey, Cumpt. rend., 1975, 280, C, 1153.

Organophosphorus Chemistry

114

2 Reactions General.-Pudovik et aZ.59have re-examined some reactions between imines and dialkyl phosphonates reported initially in 1959 by N. Kreutzkamp and G. Gordes, and they have shown that the products of the reactions between dialkyl phosphonates and (70) or (71) are actually (72) and (73), and not the bis(phosphonic acids) (74; R2 = H, Ph) (Scheme 2). They were further able to show that, under milder conditions, the imino-ethers (70) will yield eventually (77), through (75) and (76).

+ H@

Ph-C

\@ (71)

@=

Not (74; R2 = Ph)

C

H’

‘NPh@

(73)

(EtO),P(O) Scheme 2

In their attempts to prepare aminomethanebis- and tris-phosphonic acid derivatives, Gross et aL60 have observed the same phenomena. Both groups conclude that 59

60

A. N. Pudovik, M. G. Zimin, I. V. Konovalova, V. M. Pozhidaev, and L. I. Vinogradov, Zhur. obshchei Khim., 1975, 45, 30 (Chem. Abs., 1975, 82, 140262); A. N. Pudovik, V. I. Nikitina, M. G. Zimin, and N. L. Vostretsova, ibid., 1975,45, 1450 (Chem. Abs., 1975,83, 179217). H. Gross, B. Costisella, T. Gnauk, and L. Brennecke, J. prakt. Chem., 1976,318,116; H. Gross, L. Brennecke, and B. Costisella, ibid., p. 272.

115

Quiizquevalertt Phosphorus Acidr

compounds of type (74) readily undergo rearrangement, with migration of the diethylphosphoryl group from carbon to nitrogen, either in the anion of the compound (Scheme 3) or alternatively in the neutral compound, during distillation.

@ Scheme 3

Many of the reported mechanistic studies have utilized cyclic phosphorus esters, particularly of the 4-methyl-l,3,2-dioxaphosphorinansystem, employed largely by the Polish group (Stec, Michalski et aZ.), and of the bicyclic 1,3,2-dioxaphosphorinan and perhydro-l,3,2-oxazaphosphorinsystems based upon carbohydrates (Inch et aZ.). An interesting comparison has been made between the behaviour of (78)-(80) in their reaction with Cla and SOzClz.81Compounds (78) and (79) react at - 70 "C via phosphonium-like intermediates, with retention of configuration; in the former case the product is the phosphonic chloride (81) whereas (79) yields the cyclic oxophosphoranesulphenyl chloride (82). On the other hand, the benzodioxaphospholan(80) Et

'

~ o \ P 0' ~ o l c l (85)

reacts via the two pentaco-ordinate intermediates (83) and (84),both of which may be detected at -90 "C;a behaviour which is in keeping with the widely recognized ability of this ring system to participate in pentaco-ordination around phosphorus. At higher temperatures only the phosphorochloridate (85) is detectable. 61

A. Skowronska, J. Mikolajczak, and J. Michalski, J.C.S. Chem. Comm., 1975, 986.

I16

Organophosphorus Chemistry

Further elegant studies using bicyclic phosphonamidothionates and phosphoramidothioates based on D-glucopyranose have demonstrated that, with regard to P-S bond fission at least, each type behaves differentlyin nucleophilic displacements (Scheme 4). After the initial ring opening of (86) to give (87) with inversion of conMe I

I

+

MeQ

AcS

Me

MeO-

OMe

OMe

(91)

(92)

Reagents: i, dilute HCI; ii, py-AczO; iii, dilute aq. EtOH-NaOH; iv, MeI; v, NaOMe-MoOH; vi, MeOH-HCl Scheme 4

figuration at phosphorus, the further steps to (88) proceed without fission of bonds attached to phosphorus. (R)p-(88) gives (S)~-(89), the latter also being formed from (90) with configurational inversion. Thus the formation of (89) from (88) must proceed with inversion of configuration. In a similar sequence, (S)~-(91) gives (R)p-(92), indicative of retention of chirality at phosphorus. In base-catalysedhydrolysis, compound (93 ;R1 = R2 = Ph) behaves differently to (93; R1 = Me or Ph, R2 = OMe) not only with respect to reaction rate but also 62

T. D. Inch and G . J. Lewis, Carbohydrate Res., 1975, 45, 65.

Quinquevalent Phosphorus Acids

117

in the nature of the hydrolysis product. The phenylphosphonic amide hydrolyses faster than the other compounds, and also with 100% P-N bond fission, the remainder undergoing P-0 bond fission to various extents. The unusual course of this reaction prompted Hudson et al. to propose an intermediate or transition state having square-pyramidal geometry.63

Me

Ethyl methyl ethylphosphonothionate (94; X = S) and the 4-methyl-l,3,2dioxaphosphorinans (95; X = S; R = OMe or NMe,) are oxidized with 90% HzOzto the phosphoryl analogues with net retention of configuration; phosphine sulphides, in contrast, are oxidized with inversion and racemi~ation.~~ The reaction between phosphoramidate anions and COz, resulting in P-N bond fission, was first reported in the early 1960s; the fate of the phosphorus-containing moiety was not described clearly, nor were any conclusions reached as to the stereochemistry of the reaction. The reaction of the anions (96) and (97) with CO, and CS,

Products (98), (99)

(9 7)

(96)

Me

X

Reagent

Y

0

cs, co, cs, co,

0 s 0 s s s

s

Se

cs2

(98)

0 S

Z

Se Se

(99)

has now been examined further, and the nature and geometry of the phosphoruscontaining products was determined by treatment of the reaction mixtures with iodomethane and isolation of the S-methyl esters (98) and (99). In all cases, the products, as listed, possess the configuration of the starting materials.6s Reactions of Phosphoric Acid and its Derivatives.-Theoretical studies on the conformational properties of cyclic and acyclic phosphate esters, including calculations of angle and torsional strain,6s and on the reactivity of monomeric metaphosphates,67have appeared. 63

64

65 66

67

J. A. Boudreau, C. Brown, and R. F. Hudson, J.C.S. Chem. Comm., 1975, 679. W. J. Stec, A. Okruszek, and J. Michalski, J. Org. Clzem., 1976, 41, 233. W. J. Stec, A. Okruszek, K. Lesiak, B. Uznanski, and J. Michalski, J. Org. Chem., 1976,41,227. D. G . Gorenstein, D. Kar, B. A. Loxon, and R. K. Momii,J. Amer. Chem. SOC.,1976,98,1668. L. M. Loew, J. Amer. Chem. SOC.,1976,98, 1630.

5

118

Organophosphoriis Chemistry

A novel demonstration of the latent reactivity of the phosphoryl bond and the apparent ease with which the number of ligands around the phosphorus atom can change under very mild conditions is provided by the hydrogen phosphonate (loo), prepared from catechol and phosphorous acid or PCl,. When treated with DCC, (100) yields ultimately the spiran (102). An explanation for this relies on the assumption that the phosphoryl bond participates in ring-chain tautomerism involving (101).6*

When the monosodium salts of uracil and similar pyrimidines react with diphenyl phosphorochloridate, phosphorylation takes place on oxygen unless other suitable iiucleophilic centres are present and free.69The reaction between the sodium salt of a 1,3-dicarbonyl compound and diethyl phosphorochloridothionate yields the Zvinylphosphorothionate; if the tetrabutylammonium salt is employed, the product has E geometry. This phenomenon has been interpreted in terms of the shape of the

dicarbonyl anion in different solvents. Equilibria of the type (103)+(104) are also observable in such reaction mixtures. 70 Phosphorylation of phenolate anions with dimethyl phosphorochloridothionate in water-dichloromethane systems normally gives large amounts of dithiopyrophosphate because of extensive hydrolysis of the phosphorus chloride, but in the presence of tetrabutylammonium salts and 1 % imidazole, phosphorylation of the phenolate anion is complete. The explanation lies in an evident combination of activation of acylating agent (by imidazole) and of nucleophile (by phase-transfer catalysis).71 Interest in solvolysis studies of phosphate esters appears to have sagged during the year, but such studies as have appeared include those on the acid-catalysed hydro68 69

70

71

M. Gallagher, A. Munoz, G. Gence, and M. Koenig, J.C.S. Chem. Comm., 1976, 321. V. S. Reznik, Yu. S. Shvetsov, V. S. Bakulin, and I. Sh. Salikhov, Izvest. Akad. Nauk. S.S.S.R., Ser. khim., 1975, 1397 (Chern. Abs., 1975, 83, 164327); V. S. Reznik, V. S. Bakulin, Yu. S. Shvestsov, and B. E. Ivanov, ibid., 1975, 1401 (Chem. Abs., 1975, 83, 164298). H. Kolind-Anderson and S. 0. Lawesson, Acta Chem. Scnnd. ( B ) , 1975, 29, 430. R. W. Ridgway, H. S. Greenside, and H. H. Freedman, J. Amer. Chem. SOC.,1976, 98, 1979.

Quinquevalent Phosphorus Acids

119

lysis of di-4-chlorophenyl phosphate 72 and the neutral hydrolysis of 2,4-dichlorophenyl dihydrogen phosphate 73 and 5‘-aminoalkylthiophosphates and related The spontaneous hydrolytic reactivity of (105; n = 1) approximates to those of other systems which react through six-membered-ring intermediates. Comparison of the compounds (105; n = 0 or 1) suggests that such electrostatic barriers as might exist and resist the formation of cyclic transition states are overcome. An optimal size of metal ion in the catalysis of the former compound is apparent ; specific metal-ion-catalysed hydrolysis of (106) proceeds through a cyclic intermediate (transition state) after expulsion of phenol. 75 NN’-Diaryl-l,3,2diazaphospholidine 2-oxides undergo ring fission in formic acid buffers to give Nformyldiarylethylenediamines.7s Thiophosphate esters in fluorosulphonic acid protonate at (thio)phosphorylbonds, as demonstrated by lH and 31Pn.m.r. spectroscopy. Thionophosphate esters undergo isomerization to the thiolate in the presence of 1-3 molar proportions of TFAA at room temperature, probably by initial protonation at the thiophosphoryl bond. In suitable cases, the reaction can be shown to proceed with inversion of configuration.7 8

Further examples of the effects of added cations on stereochemical pathways have been observed using 5-chloromethyl-5-methyl-2-oxo-1,3,2-dioxaphosphorinans. Under normal conditions, methanolysis of (107; R = SPh) leads to the methoxyester having the same configuration. In the presence of added cations, particularly Li+,both inversion and retention pathways are Phenolysis of the phosphorochloridate (107; R = Cl), normally proceeding with inversion, proceeds with complete retention of configuration in the presence of Li+.80 Diastereoisomeric cyclic isothiocyanates (1 11) are formed when the bromidates (108; X = Br) react with KCNS, and when the hydrogen phosphonates (108; X = H) are treated with (SCN)2; these reactions proceed with predominant retention and with inversion of configuration, respectively.*l This initial study of the formation of the thiocyanatidates (109) was rendered difficult by the rapid epimeriza72 73 74 75

76 77 78

79

81

M. M. Mhala, M. D. Patwardhan, and S. Doebhakta, J. Indian Chem. SOC.,1975, 52, 931. M. M. Mhala, S. S. Bhatawdekar, and R. N. Sharma, Current Sci., 1975,44, 687 (Chem. Abs., 1976, 84, 4080). S . A. Grachev, E. V. Kropachev, and G. I. Litvyakova, Zhur. obshchei Khim., 1975, 45, 1461 (Chem. Abs., 1975, 83, 130828). J. J. Steffens, I. J. Sewers, and S. J. Benkovic, Biochemistry, 1975, 14, 2431. B. A. Amato and S. J. Benkovic, Biochemistry, 1975, 14, 4877. G. A. Olah and C. W. McFarland, J. Org. Chem., 1975,40, 2582. W. J. Stec, B. Uznanski, K. Bruzik, and J. Michalski, J. Org. Chem., 1976, 41, 1291. W. S. Wadsworth, jun., and R. L. Wilde, J.C.S. Chem. Comm., 1976, 93. W. S. Wadsworth, jun. and R. L. Wilde, J. Org. Chem., 1976,41, 1264. A. Lopusinski, J. Michalski, and W. J. Stec, Bull. Acad. polon. Sci., Se‘r. Sci. chim., 1975, 23, 229 (Chem. Abs., 1975, 83, 147457).

120

OrganophosphorusChemistry

Me

(111)

tion of cis-(109) into the trans-form. A more detailed study of the thiocyanate to isothiocyanate rearrangement, (109) + ( l l l), was permitted, however, when it was found that, at - 15 “C, AgCN and the oxyphosphoranesulphenylchloride (108; X = SCl) react to give the thiocyanate (109); trans-(108; X = SCl) yields only the trans-(109), whereas cis-(108; X = SCl) is much less specific in its reaction, yielding a 2:l mixture of isomers, with favoured retention of configuration. The non-stereospecific isomerization (109) +(ll 1) takes place in the presence of the ambident thiocyanate anion, and has been formulated as proceeding through the intermediate (1 Bearing in mind the known tendency of the ‘hard’P=O to be attacked by the ‘harder’ portion of an ambident nucleophile, it may well be that, in the reaction between (108; X = Br) and KCNS, (111) is formed directly rather than through (109). The fission of the disulphide bond in bis(dialkoxyphosphiny1)disulphides by CNto give monothiopyrophosphateshas been interpreted in terms of initial formation of phosphorylthiocyanate (Scheme 5). 83

ii J A

-S--PR,

yp-\

CN

0

I/

R,P-SCN

+

&P

40 1 -

IL

0

II &P-NCS

0

S

II I1 &P-O-PR,

Scheme 5

On the basis of earlier studies on reactions between trialkyl phosphites and oxophosphoranesulphenyl chlorides, Gusar’ et al. predicted that the latter should react with diethyl phosphorochloridite (1 12; X = OR1 = OEt) and ethyl phosphorodichloridite (112; X = C1; R1 = Et) according to pathway (a). The unexpected *2

83

A. Lopusinski, J. Michalski, and W. J. Stec, Bull. Acad.polon. Sci.,S&. Sci. chim., 1975,23,235 (Chem. A h . , 1975, 83,96249). A. Lopusinski and J. Michalski, Bull. Acac?. polon. Sci., Shr. Sci. chim., 1975, 23, 411 (Chem. A h . , 1975, 83, 97476).

Quinquevalent Phosphorus Acids

121

observation that the pathway is (b) was explained in terms of the transformation (1 13)+(114) in an intermediate.s4The corresponding reaction with PCl, yields (1 15)

R’O-P

,’c1 \

-t

(R’OXP

/O

\scl

X

(112)

R’O ‘P”

x’ \cl

-t

(RQ),P

//O

‘a

c1-

and POCl when an acyclic oxophosphoranesulphenyl chloride is employed, taking place with inversion of configuration. Cyclic oxophosphoranesulphenyl chlorides undergo simultaneous desulphurization (with retention of configuration) and deoxygenation (with inversion of configuration).85 Oxophosphoranesulphenamides,obtainable with difficultyfrom oxophosphoranesulphenyl chlorides and amines, are readily obtained from the m i n e and bis(dialkoxyphosphinyl) disulphides deoxygenation and desulphurization of the sulphenamides has been observed (Scheme 6).8 7 (Me,N),PF + (Et,N),P(O)SNEt,

loooc:

(Me,N),P(S)F + (EtO),P(O) NEt,

(Me,N)(Et,N)P(S)F: t (EtO),P(Q)NMe,

Scheme 6 84 85

88

87

N. I. Gusar’, Zh. M. Ivanova, M. G. Tret’yak, V. S. Sergeev, and Yu. G. Gololobov, Zhur. obshchei Khim., 1975,45, 734 (Chem. Abs., 1975, 83, 9087). J. Omelanczuk, P. Kielbasinski, J. Michalski, J. Mikolajczak, M. Mikolajczyk, and A. Skowronska, Tetrahedron, 1975, 31, 2809. N. N. Mel’nikov, B. A. Khaskin, and N. A. Torgasheva, Zhur. obshchei Khim., 1975,45, 1005 (Chem. Abs., 1975, 83, 58008). N. I. Gusar’, M. P. Chaus, and Yu. G. Gololobov, Zhur. obshchei Khim., 1975,45, 1894 (Chem. Abs., 1975, 83, 178212).

122

Organophosphorus Chemistry

When the phosphoramidic difluoride (1 16) reacts with diols, alkanolamines, or diamines, the manner of ring closure is dependent on n in a way which is both novel, and, from the synthetic viewpoint, potentially useful, although for compounds for which n = 2 a mixture of products (117; R = F or Me,N) may result.88

Earlier claims for the preparation of methyl metaphosphate, if only in situ, have received further support by the observation that the species, thought to be (119), will attack NN-diethylaniline at low temperatures to give methyl 4-NN-diethylaminophenylphosphonate.8gThe formation of 00s-triethyl phosphorodithioate together with triethyl thionoformate when triethyl orthoformate is treated with P2S5or diethyl hydrogen dithiophosphate is interpreted in terms of the species (1 20).0°

(E t O), I'(0) N 11Me Me1 11,O

+

~

(Et Q), P(S) NMe,

The ambident nature of the anion (121) affords an explanation for the formation of both 00-diethyl N-methylphosphoramidate and 00-diethyl NN-dimethylphosphoramidothionate when diethyl N-methylphosphoramidothionate anion is treated with iodomethane, followed by aqueous work-up.91 The ambident phosphorothioate anion (122) yields 0-metalloidal derivatives when treated with chlorides of Group IV elements.92

(122)

M = Si, Ge, or Sn; R = Me or I'h

Nitration of diethyl N-phenylphosphoramidate and diethyl phenyl phosphate in acetic anhydride or sulphuric acid yields considerable amounts of the m-nitro88 89

91 92

J. Amos, R. A. Chittenden, and G . H. Cooper, Phosphorus, 1975, 6, 35. C. H. Clapp, A. Satterthwaite, and F. H. Westheimer, J. Amer. Chem. Soc., 1975, 97, 6873. B. K. Athawale, J. B. Chattopadhyaya, and A. V. R. Rao, Indian J. Chem., 1975, 13, 812. M. Drew and P. Savignac, Compt. rend., 1975, 280, C , 297. L. A. Duncan and C. Glidewell, J . Organometallic Chenr., 1975, 97, 51.

Quinquevalent Phosphorus Acids

123

products in addition to o- and p-nitro-compounds.93 Diphenyl phosphorazidate and diethyl phosphorocyanidate are useful reagents for the formation of peptides even in solid-support work.94 Phosphoramidates continue to attract much attention, not only with regard to their interest in organophosphorus chemistry but also in the context of general organic synthesis. Acid hydrolysis of the phosphoramidates (123) and (124) with 0

0

0

II qP-NHR'

II -* R:P-NRzCH$ECH

R' = EtOorMe,N

. Nf

*

II

R:P-NRzCH,C~CR3

\N-HCI

RZNHCH,C

0

II $P-NRZCH=C=CH, (1 25) R' = EtO or M%N

CH

RzN HC&C

CR3

0 -I-~

II

P-NRzC~CMe (126)

R' = Me,N

3N-HCl affords aminopropynes. Treatment of (123) with NaH gives pure (125) when R1 = OEt, but a mixture of (125) and (126) if R1 = Me2N.95 (EtO),P(O) NCI,

R'R'C =CH R'

(EtO),P(0)NCICIIR'CHCIR'RZ

\

i, NaHCO,;

3, alc. KOH

The N-phosphorylated aziridines (127) are conveniently obtained by intramolecular cyclization of N-2-chloroethylphosphoramidateanions. The latter can be obtained by addition of NN-dichlorophosphoramidates to alkenes and hydrolytic removal of the chlorine on n i t r ~ g e n . ~ ~ A synthesis of alkenes from 1,2-diols depends upon the initial formation of the 1,3,2-dioxaphospholans (128), followed by rupture of the heterocyclic ring and removal of phosphorus with Li-NH, or Na-C,,H,. The reaction is reasonably stereo93 g4 95

96

T. A. Modro and J. Pioch, Canad. J. Chem., 1976,74, 560 S. Yamada, Kagaku Kogyo, 1975,26,153 (Chent. A h . , 1975,83,10798); S . Yamada, N. Ikoto, T. Shiori, and S. Tachibana, J. Amer. Chem. SOC.,1975, 97, 7174. B. Corbel, J.-P. Paugam, M. Dreux, and P. Savignac, Tetrahedron Letters, 1976, 835. A. M. Pinchuk, T. V. Kovalevskaya, and G . K. Bespal'ko, Zhur. obshchei Khim., 1975,45,1240 (Chem. Abs., 1975, 83, 178661).

I24

Organophosphorirs Chemistry

selective; threa-2,3-dihydroxydecaneyields a 90 :10 mixture and erythro-decanediol a 20: 80 mixture of E- and 2-2-de~enes.~' Interest in the uses of HMPT has also been maintained, but a warning has been issued (by the E. I. du Pont de Nemours Company and the U.S. National Institute for Occupational Safety and Health) about its potential acute toxicity. HMPT has been as a solvent for reactions used in the synthesis of 2,4-bis(dirnethylamino)q~inolines,~~ between carbonyl compounds and sulphur, 9 9 for the conversion of N-benzylcarboxin reactions between metals or organometallic amides into 3-phenylpropionitrile~,~~~ compounds with a variety of organic substrates,101and as a solvent for alkylation reactions of p-keto-esters and related compounds in which the alkylation reaction is accompanied by de(alkoxycarbony1ation) (Scheme 7).lo2

Scheme 7

Oxirans are converted into thiirans when treated with 00-diethyl hydrogen dithiophosphate.lo3 Reactions of Phosphonic and Phosphinic Acid Derivatives.-The react ions of phosphonic and thiophosphonic amides and chlorides with carboxylic acid chlorides and amides have been discussed.lo4Dialkyl alkylphosphonates and alkyl dialkylphosphinates may be used for the N-alkylation of imidazoles, triazoles, and p y r r o l e ~ . ~ ~ ~ Diethyl perfluoroacylphosphonates, e.g. (129), undergo easy solvolysis and hydrazinolysis with P-C bond fission to give the perfluoroacyl derivatives (13O).lo0 The J. A. Marshall and M. E. Lewellyn, Synrh. Comm., 1975,5, 293 (Chem. Abs., 1975,83,96474). E. B. Pedersen, Acta Chem. Scand. ( B ) , 1976, 30, 133. 99 J. Perregaard, I. Thomsen, and S. 0. Lawesson, Acta Cltem. Scand. ( B ) , 1975,29, 538, 599; J. Perregaard and S. 0. Lawesson, ibid., p. 604. l o o H. J. Meyer, J. Goldman, E. B. Pedersen, and S. 0.Lawesson, Bull. SOC.chim. belges, 1975,84, 735 (Chem. Abs., 1975, 83, 178521). l01 For example R. 0. Hutchins, F. Astone, B. Goldsmith, and P. Herrman, J. Org. Chem., 1975, 40,2018; Y. Ohbe and T. Matsuda, Bull. Chem. SOC.Japan, 1975, 48, 2389; T. Cuvigny, M. Larcheveque, and H . Normant, Annalen, 1975, 719; W. Kotlarek, J. Org. Chem., 1975, 40, 2841. M. Asaoka, K. Miyake, and H. Takei, Chem. Letters, 1975, 1149 (Chem. Abs., 1976, 84, 1671 1). 103 0. N. Nuretdinov, G . A. Bakaleinik, and B. A. Arbuzov, Izoest. Akad. Nauk. S.S.S.R., Ser. khim., 1975,962 (Chem. Abs., 1975, 83,97586). l o 4 A. V. Grapov, L. V. Razvodovskaya, and N . N. Mel'nikov, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 5rh, 1972 (publ. 1974), 254 (Chem. Abs., 1975, 83, 147521). l o 5 M. Hayashi, K. Yamauchi, and M. Kinoshita, Bull. Chem. SOC.Japan, 1976, 49, 283. 106 I. L. Knunyants, E. G . Bykhovskaya, Yu. A. Sizov, and L. I. Zinov'eva, Zhur. he$. Khim. 0-va., 1975, 20,235 (Chem. Abs., 1975, 83, 97463). 97

9R

Quinquevaleat Phosphorus Acids

125

same fluorinated phosphonates also react with dialkyl hydrogen phosphonates; the unusual products, containing both P-C and P-0 bonds to the original acyl carbonyl carbon, are evidently the result of a rearrangement which also takes place when the perfluoroacylphosphonatesare treated with HCN to give phosphates, e.g. (132).lo7 0

0

II II (EtO),P-CC,F,

-% C,F,COR

.t

(EtO),P(O)H

(130)

R = HO, E t 0 , o r NHNHC,H,NO,-4

Aroylphosphonates undergo conversion, in high yield, into aroylmethylphosphonates [(133)+(134)] when they react with diazomethane at 0 O C , l o 8 and they also react photochemically with 3-phenyl-2H-aziridines to give C-phosphorylated oxazolines (135).Io9

R

0

II (EtO),PCOR

+

_hv,

Me,a

R

Ph

Nvo

= PhorOEt

The thermal polymerization of the fluorinated 1,3,2-dioxaphosphorinans(136) I. L. Knunyants, E. G. Bykhovskaya, Yu. A. Sizov, and L. I. Zinov'eva, Zhur. Yses. Khim. O-ua., 1975, 20, 236 (Chem. Abs., 1975, 83, 97464). lo*D. Kost and M. S. Sprecher, Tetrahedron Letters, 1975, 4483. log N.Gakis, H. Heimgartner, and H. Schmid, Helv. Chim. Acta, 1975, 58, 748. 107

126

Orgutlophosphorus C h z i s t r y

takes place with greater ease as the group R becomes increasingly electronattracting.llo

In reactions between the cyclic phosphonic chloride (137) and the diols (138), the composition of the reaction products that have not been thermally treated differ widely, depending on n, the compound (139) that is initially formed evidently undergoing further change. When n=2, the product then consists of either (140) or (141)

(141)

whereas if the hydroxylic starting material is propane-l,2-diol the mixture of reaction products also contains the cyclic phosphonate (142). In general, an increase in the number of substituents in the carbon chain of the diol favours a cyclic product.lll Several addition reactions of mono- and di-enephosphonates have been reported. Diethyl vinylphosphonate reacts at 100 "C with cyclohexanone pyrrolidenamine in a stepwise fashion. Hydrolysis of the initial adduct yields the ketophosphonate (143) but further reaction of the adduct in a Mannich-type process can yield, ultimately, the cyclobutenylphosphonate (144).l12 Diethyl butadienephosphonate condenses 110

111

112

V. N. Sharov, A. L. Klebanskii, V. V. Korol'ko, and G . P. Kondratenkov, Vysoknmnl. Soedineniya, 1975,17, B, 791 (Chem. Abs., 1976, 84, 31 61 1). B. A. Arbuzov, A. 0. Vizel', K. M. Ivanovskaya, and E. I. Gol'dfarb, Zhur. obshchei Khim., 1975,45, 1223 (Chem. Abs., 1975, 83, 131684). S . D. Darling and N. Subramanian, Tetrahedron Letters, 1975, 3279.

Quinquevalent Phosphorus Acids

127

similarly, yielding several products, including a hexahydronaphthalene,this sequence being the first recorded addition of a diene phosphonate to an enamine.l13

N-Aminophthalimide and dimethyl vinylphosphonate interact in the presence of lead tetra-acetate to give the compounds (145) and (146) in approximately equal 0

amounts. It would seem that (146) is formed by thermal rearrangement of (145), the expected product of addition of phthalimidonitrene to the vinylph~sphonate.~~~ Addition of amines to allenephosphonatesyields C-phosphorylated enamines, the stereochemistry of which partly depends on the nature of R2and R3 (147). When R2 is hydrogen, intramolecular hydrogen bonding with the phosphoryl group is possible in the 2-isomer, and indeed this is the isomer which is then produced in greater yield. The carbon-carbon double bond can be reduced with KBH4.llS ll8 11* 115

S. D. Darling and N. Subramanian, J. Org. Chem., 1975,40, 2851. F. V. Bagrov, Zhur. obshchei Khim., 1975, 45, 947 (Chem. Abs., 1975, 83, 43452). J. V. Merour, Nguyen Thanh Thuong, and P. Chabrier, Compt. rend., 1975,280, C, 473.

128

w,/ ! CH-C-CH,

R:

=

(Bu'O), or

+ R2R3NH

c:

-

Organophosphoriis Chemistry

R:P No

\CH=CMeNRZR3 (147)

Other vinylphosphonates, e.g. (148), undergo reactions with hydrazines, hydroxylamines, or amidines to yield C-phosphorylated 1,2-diazoles, 1,2-oxazoles, or 1,30

)=CR'SMe

CN

diazines, e.g. (149).ll6 The pyridines (150) may be dephosphonylated by heating them with 20 % HCl.l17 Reduction of the diazaphospholines (151) by trichlorosilane yields a mixture of cis- (R2= H, R3 = Ph) and trans- (R2= Ph, R3 = H) phosphines, the lack of stereospecificity being attributed to changes in a pentaco-ordinate intermediate. Stereomutation of the starting oxide is brought about by hexachlorodisilane or silicon tetrachloride.ll8

R = alkyl or aryl

(152)

A study of the kinetics and products of the thermolysis of a series of diarylphosphinic azides has been reported.llg Diethyl l-diazomethylphosphonatesundergo an aldol-type reaction with aldehydes to give l-diazo-2-hydroxyalkylphosphonates (152).lZ0Acidificationof the diazophosphonates(153) possessing a chiral phosphorus centre yields mixtures of diastereoisomers (154) and epimers at C. For given R1 and R2,the reaction becomes increasingly stereoselectivefor X= OAc < C1< OTs. It may be argued that protonation of (153) will yield a mixture of diastereoisomeric di116 117 118

119

120

0. Guenther and K. Hartke, Arch. Pharm., 1975, 308, 693. L. Achremowicz, Synthesis, 1975, 653. G. Baccolini and P. E. Todesco, J. Org. Chem., 1975, 40, 2318. F. Weissbach and W. Jugelt, J. prakt. Chem., 1975, 317, 394. W. Disteldorf and M. Regitz, Chem. Ber., 1976, 109, 546.

129

Quinquevalent Phosphonis Acids 0

0

R2 MeO':!

C"

(153)

HX several ' ~

steps

(154)

azonium salts, the relative amounts of these depending on the probabilities of proton approach from one or other diastereotopic side. Loss of nitrogen proceeds with the formation of a planar (at carbon) cation, which then undergoes reaction with the anion X- to give diastereoisomeric products (154), the relative proportions of which will depend on the sizes of R1, R2, and X.121 Further studies on lY3-dipolaraddition reactions of diazophosphonates have been recorded,122and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155; R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbony1)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155; R = Me) does not react in the manner described above.

When a solution of the ester (155; R = H) in dioxan is warmed at 80 "C,the phosphonate (156) is produced together with about 5 % yields of each of dimethyl hydrogen phosphonate and diazoacetoacetic ester (Scheme 8) ; the enol phosphate (157) could not be detected. The explanation for this sequence of reactions also relies on proton mobility, and the reaction is known to be acid-~ata1ysed.l~~ The deselenization of t-butyl phenylphosphinoselenoic acid by Raney nickel is highly stereoselective, allowing a stereochemical correlation between the selenoate and the analogous phosphorothioic acid through a common intermediate.126 121

R. D. Gareev and A. N. Pudovik, Zhur. obshchei Khim., 1975,45,942 (Chem. Abs., 1975,83, 9009).

122 123

H. Cohen and C. Benezra, Canad. J. Chem., 1 9 7 6 , 5 4 4 4 . A. N. Pudovik and R. D. Gareev, Zhur. obshchei Khim., 1975,45, 16 (Chem. Abs., 1975, 82,

124

A. N. Pudovik and R. D. Gareev, Zhur. obshchei Khim., 1975, 45, 22 (Chem. Abs., 1975, 82,

126

J. Michalski and Z. Skrzypzynski, J. Organometallic Chem., 1975, 97, C31.

111231). 171 149).

130

Organophosphorus Chemistry

It .

OEt

OEt

.-

&+AHI

CO, E t

Scheme 8

The acid-catalysed hydrolysis of phosphinic esters (158) is relatively insensitive to the substituent (R = Me, Et, Pri, or But) attached to phosphorus; this contrasts with the base-catalysed process.126The acid hydrolysis of the phosphinic esters (1 59) (see ‘Organophosphorus Chemistry’, Vol. 7, p. 129 for the base hydrolysis) takes place with alkyl-oxygen fission in an S Nprocess.127 ~

R

A range of mechanisms is possible for the acidolysis of phosphorus amides, depending on the nucleophilicity of the departing amine. A recent study of phosphinic amides (160) in acidic media demonstrated that, when R2is aryl, the presence of an o-Me group reduced the hydrolysis rate significantly, and also that the mechanism appears to be of an associative type.12sThe phosphinic halides (161 ;X = CI or F; R = Me) are more reactive, probably for steric reasons, than the corresponding ) with aqueous acetone and with alkali. halides (161 ; R = But) in S N ~ ( Psolvolyses In the case of the t-butyl compounds, the fluoride is more reactive to OH- than is the

126 127 128

lZ9

K. Abbas and R. D. Cook, Tetrahedron Letters, 1975, 3559. A. I. Razumova, I. A. Krivosheeva, B. G . Liorber, T. A. Tarzivolova, and V. A. Pavlov, Zhur. obshchei Khim., 1975,45, 1946 (Chem. Abs., 1976,84,4051). A. C. Clements, M. J. P. Harger, A. Leonard, and M. D. Reed, TetrahedronLetters,1976,493. R. J. Brooks and C. A. Bunton, J. Org. Chem., 1975, 40, 2059.

Quinquevalent Phosphorus Acids

131

Mechanistically, the compounds (162; X = 0 or S ) and (163) represent two extremes in the base hydrolysis of phosphoramidates and phosphoramidothioates; the former hydrolyse in an elimination-addition (EA) process whereas for the latter the sequence is one of addition followed by elimination (AE). Further exploration of

.

.

(163) (164) the borderline between these extremes has been described. The phosphonic derivatives (164) lose ArO- in the presence of base, with mechanisms that are dependent on X. Thus, when X is oxygen, the mechanism is EA whereas for the thioate series the mechanism is In reactions between methylmagnesium iodide and 0-alkyl S-methyl phenylphosphonothiolate, the mechanistic pathway, i.e. displacement of OR or SMe, depends on the bulk of the group R (Me, Pri, or menthyl). The bulkier is R, the more extensive is the P-S bond

3 Structure Using n.m.r. methods and dipole-moment measurements, configurational assignments have been made for a series of 5-alkyl-5-nitr0-1,3,2-dioxaphosphorinans,~~~ cis- and trans-isomers of 2-substit~ted-3-methyl-l,4,2-dioxaphosphorinans,~~~ and of perhydro-1,4,2-0xazaphosphorins,~~~ have been recognized. Other assignments of molecular geometry have been made to various 4-methyl-1,3,2-dioxaphosphoriin the n a n ~ , some l ~ ~ of which have been confirmed by crystallographic same system the axial preference for the a n i l i n ~ - , methylthi~-,l~~ l~~ ~ y a n o - and ,~~~ fluoro- 140 groups has been confirmed. cis- and trans-isomers of the imidazolium salts of C-substituted 2-hydroxy-l,3,2dioxaphospholan-2-thiones have been separated and characterized by both spectral and crystallographic methods.141In the eight-membered ring of 2-methyl-6-phenyl-6 Williams, K. T. Douglas, and J. S. Lovan, J.C.S. Perkin ZI, 1975, 1010. F. DeBruin and D. M. Johnson, J.C.S. Chem. Comm., 1975, 753. 132 B. A. Arbuzov, R. P. Arshinova, T. A. Guseva, T. A. Zyablikova, L. M. Kozlov, and I. M. Shermergorn, Zhur. ubshchei Khim., 1975, 45, 1432 (Chem. Abs., 1975, 83, 179215). 133 M. V. Sigalov, V. A. Pestunovich, V. I. Glukhikh, M. Ya. Khil'ko, V. M. Nikitin, M. F.Larin, and B. A. Trofimov, Zzoest. Akad. Nauk. S.S.S.R., Ser. khim., 1975, 1761 (Chem. Abs., 1976, 84, 4333). 134 Yu. Yu. Samitov, M. A. Pudovik, L. K. Kibardina, and A. N. Pudovik, Zhur. obshchei Khirn., 1975,45,2134 (Chem. Abs., 1976, 84,43 158). 135 W. J. Stec, K. Lesiak, D. Mielczarek, and B. Stec, Z. Naturforsch., 1975, 30b, 710; W. J. Stec, R. Kinas, and A. Okruszek, 2. Naturforsch., 1976, 31b, 393; T. J. Bartczak, A. Christensen, R. Kinas, and W. J. Stec, Tetrahedron Letters, 1975, 3243. 136 T. J. Bartczak, A. Christensen, R. Kinas, and W. J. Stec, Cryst. Struct. Comm., 1975, 4, 701 ; ibid., 1976, 5, 21. 13' W. J. Stec and A. Okruszek, J.C.S. Perkin Z, 1975, 1828. l38 A. Okruszek and W. J. Stec, Z . Naturforsch., 1975, 30b, 430. 13s B. Uznanski and W. J. Stec, Synthesis, 1975, 735. 140 A. Okruszek and W. J. Stec, 2. Naturforsch., 1976, 31b, 354. 141 M. Mikolajczyk, M. Witczak, M. Wieczorek, N. G. Bokij, and Yu. T. Struchkov, J.C.S. Perkin J. 1976, 371. 130 A. 131 K.

132

Organophosphorus Chemistry

aza-l,3,2-dioxaphosphocan2-oxide, bonds attached to phosphorus form a distorted tetrahedron, while those at nitrogen are ~ 1 a n a r . l ~ ~ The addition of oxygen, sulphur, or selenium to 2-hydro-4-methyl-l,3,2-dioxaphosphorinan proceeds stereo~pecifically.~~~

142

143

A. E. Kalinin, V. G. Andrianov, and Yu. T. Struchkov, Zhur. strukt. Khim., 1975, 16, 1041 (Chern. Abs., 1976,84, 164077). W. J. Stec, Khim. Primen. Fosfororg. Soedin., Tr. Konf., 5th, 1972 (publ. 1974), 351 Chem. Abs., 1976, 84, 17295).

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

1 Introduction Magnetic resonance techniques have again been popular for studying enzymes which are involved in phosphate hydrolysis and transfer. 31Por l9F N.m.r.lS2 and spinlabelling3 have all been used to study the interaction of substrates with these enzymes, while affinity labelling4is another technique which has been used to obtain information about the sequence and conformation of amino-acid chains at the active sites of enzymes. Recently, these experimental methods have been applied to the study of cell membrane^,^-^ and these are mentioned in a new series of books concerned with enzymes in biological membranes.s A new journal, Trends in Biochemical Sciences, which contains concise, up-to-date reviews on these and other topics is published by Elsevier on behalf of the International Union of Biochemistry. Affinity chromatography and the insolubilization of enzymes continue to attract attention. Affinity chromatography is now used routinely for the purification of enzymes and other macromolecules; reference to this technique will be made in the various sections of this Chapter. Immobilized enzymes have great industrial potential as, unlike soluble enzymes, they can be re-used, thus reducing significantly the cost of a product. A new development mentioned in last year’s ReportQ is the use of insolubilized enzymes as analytical tools, when advantage can be taken of the sensitivity and selectivity of the enzymic reaction. Immobilized enzyme reactors have been made which can detect inorganic phosphate, organophosphorus insecticides, and other phosphate esters.1° This technique will, no doubt, be used extensively in the future.

W. E. Hull, S. E. Halford, H. Gutfreund, and B. D. Sykes, Biochemistry, 1976, 15, 1547. W. E. Hull and B. D. Sykes, Biochemistry, 1976, 15, 1535. S. J. W. Busby, M. A. Hemminga, G. K. Radda, W. E. Trommer, and H. Wenzel, European J. Biochem., 1976, 63, 33. S. B. Easterbrook-Smith,J. C. Wallace, and D. B. Keech, European J. Biochem., 1976,62, 125. B. de Kruijff, P. R. Cullis, G. K. Radda, and R. E. Richards, Biochim. Biophys. A d a , 1976,419, 411; A. C. McLaughlin, P. R. Cullis, M. A. Hemminga, D. I. Hoult, G. K. Radda, G. A. Ritchie, P. J. Seely, and R. E. Richards, F.E.B.S. Letters, 1975, 57, 213. A. H. Ross and H. M. McConnell, Biochemistry, 1975, 14,2793, 4776. B. E. Haley and J. F. Hoffman, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 3367. ‘The Enzymes of Biological Membranes’, ed. A. Martonosi, Plenum Press, New York, 1976, Vols. 1 and 2. D. W. Hutchinson, Organophosphorus Chem., 1976, 7 , 132. l o L. D. Bowers and P. W. Carr, Analyt. Chem., 1976, 48, 545A.

133

134

Organophosphorus Chemistry

2 Coenzymes and Cofactors Nicotinamide Nuc1eotides.-A number of dehydrogenases have been purified by affinity chromatography, using NAD+ linked to insoluble supports either through the 6-113l2 or the 8-positions13of the adenine nucleus. The reverse process, the use of immobilized dehydrogenases to purify NAD+, has also been described re~ent1y.l~

3-Iodopyridine-adenine dinucleotide (1; X = I, Y = H) has been prepared by transglycosidation with NAD+ using a nucleosidase from pig brain.lS Alternatively, diazotization of 3-aminopyridine-adeninedinucleotide in the presence of the cuprous salt of the appropriate halide ion leads to (1; X = F, C1, Br, or I; Y = H). The halogeno-analogues are competitive inhibitors with respect to NAD+ for several dehydrogenases,and since they bind strongly to these enzymes they could be used as heavy-atom derivatives of NAD+ in X-ray crystallographic studies. An oestradiol 17b-dehydrogenasefrom human placenta will accept NAD+ analogues substituted in either the pyridine (1; X = CN or MeCO, Y = H) or purine (1; X = H, Y = Br or SH) rings.16 The purine-substituted analogues are good hydrogen acceptors for this dehydrogenase, which means that there can be few steric requirements at the active site of this enzyme, as the purine ring must be in the syn- rather than the anti-conformation relative to the sugar in these analogues. Substituted NMN+ derivatives have been prepared by cleaving the corresponding NAD-+or NADP+ with a pyrophosphatase from crude snake ven0m.l' While AMP is completely hydrolysed by this crude enzyme, these NMN+ derivatives are comparatively stable. The binding of NAD+ or NADH to lactate18 or D-glyceraldehyde3-phosphate19 dehydrogenases involves the pyrophosphoryl group. Data recently obtained from 31Pn.m.r. of these enzymes show that the environments of the pyrophosphoryl group N. A . Nwokoro and H. Schachter, J . Biol. Cliem., 1975, 250, 6185. M. J. Comer, D . B. Craven, M. J. Harvey, A . Atkinson, and P. D. G . Dean, Eziropean J . Biochem., 1975, 55, 201. 13 P. Zappelli, A. Rossodivita, G. Prosperi, R. Pappa, and L. Re, European J. Biochent., 1976, 62, 211. 14 K. Das, P. Dunnill, and M. D . Lilly, Biochim. Biophys. Acta, 1975, 397, 277. 15 M. A. Abdallah, J. F. Biellmann. J. P. Samama, and D . Wrixon, EltropeanJ. Biochem., 1976,64,

11 12

16

17 18

19

351. J. F. Biellmann and C. G . Hirth, European J . Biochem., 1975, 56, 557. W. Hensel, D. Rakow, and W. Christ, Analyt. Biochem., 1975, 68, 128. M. J. Adams, M. Buchner, K. Chandrasekhar, G . C. Ford, M. L. Hackert, A. Liljas, M. G , Rossmann, E. I. Smiley, W. S . Allison, J. Everse, N. 0. Kaplan, and S. S. Taylor, Proc. Nut. Acad. Sci. U.S.A., 1973, 70, 1968. M. Buchner, G. C. Ford, D. Moras, K. W. Olsen, and M. G . Rossman, Proc. Nut. Acacl. Sci. U.S.A., 1973, 70, 3052.

135

Phosphates and Phosphonates of Biochemical Interest

of NAD+ and NADH are the same for a given dehydrogenase but are different in the two enzymes.2oSince NADH binds lo3 times more strongly than NAD+ to lactate dehydrogenase, the difference in binding strengths between the reduced and oxidized forms of the coenzyme cannot be due to differences in the conformation of the pyrophosphoryl group. Flavin Coenzymes.-5-Deazaflavin-adenine dinucleotide (2) can be prepared from the 5-dea~aFMN,~l using a FAD pyrophosphorylase from rat liver.22When the apoprotein of D-amino-acid oxidase from pig kidney is reconstituted with (2), no oxidation of D-alanine is observed, although the flavin chromophore in the reconstituted enzyme is reduced on the addition of DL-amino-acids.22This has been interpreted as indicating that hydrogen transfer from the amino-acid to (2) can still CH,(CHOH),CH,OR

CH,(CHOH),C&OR

take place. An alternative synthesis of (2) has been and it has been observed that (2) binds to a number of enzymes in a manner remarkably similar to the natural FAD. The reduction of (2) to (3) can take place both chemically and en~ymically.~~ 2-Hydroxy-but-3-ynoic acid (4) inactivates L-lactate oxidase from Mycobacterium smegmatis and modifies enzyme-bound FMN in this system.26The initial adducts formed from (4) and FMN are unstable, however, and reduction of these adducts with borohydride can lead to the release of ( 5 ) (see Scheme 1). The structure of this adduct is very different from that (6) formed in the reaction of NNdimethylpropargylamine and monoamine oxidase, another flavin enzyme.26This indicates that the substrates may not be bound to the two different enzymes in the same position relative to the flavin moiety, and hence D-amino-acid and monoamine oxidases may function by different mechanisms. Pyridoxal Phosphate.-Analogues of pyridoxal and pyridoxamine 5’-phosphates have frequently been used to probe the size and shape of the active sites of a number of enzymes. For example, the apoenzyme of a tryptophanase from BaciZZus aluei will bind pyridoxal 5’-phosphate as well as the 2-nor, 2’-methyl, 2’-hydroxy, 6-methyl, and N-oxide analogue^.^' No analogue that has been modified at C-4 binds to the enzyme, confirming the absolute requirement for Schiff-base formation between the 2*

21 22

23 24 25

M. Blumenstein, Biochemistry, 1975, 14, 5004. M. S. Jorns and L. B. Hersh, J. Biol. Chem., 1975, 250, 3620. L. B. Hersh and M. S. Jorns, J . Biol. Chem., 1975, 250, 8728. R. Spencer, J. Fisher, and C. Walsh, Biochemistry, 1976, 15, 1043. J. Fisher, R. Spencer, and C. Walsh, Biochemistry, 1975, 15, 1054. A. Schonbrunn, R. H. Abeles, C. T. Walsh, S. Ghisla, H. Ogata, and V. Massey, Biochemistry, 1976,15, 1798.

28

27

A. L. Maycock, R. H. Abeles, J. I. Salach, and T. P. Singer, Biochemistry, 1976, 15, 114. H. C. Isom and R. D. DeMoss, Biochemistry, 1975, 14, 4291, 4298.

Organophosphorus Chemistry

136

CH, (C 140I{)$

I

HCSCCHOHC0,H

€60R

-t FAD

(4)

HC=CC&NMe,

+ FAD

a

R = adenosine 5’-pyrophosphoryl \&Me, (6 ) Reagents: i, L-lactate oxidase; ii, NaBH,; iii, MeOH; iv, monoamine oxidase; v, proteolytic digest

Scheme 1

pyridoxal and the enzyme for the catalytic reaction to occur. Treatment of pyridoxamine 5’-phosphate with an equimolar amount of 1 ,S-difluor0-2,4-dinitrobenzene leads to 4’-N-(2,4-dinitro-5-fluorophenyl)pyridoxamine5’-phosphate (7), which has been used as an affinity label for a number of enzymes, e.g. tryptophanase.28Presumably (7) reacts with an amino-acid other than the catalytically important lysine,

owing to steric considerations, as the latter must lie close to the carbon atom at position 4 of the pyridine ring, and the size of the 2,4-dinitro-S-fluorophenylgroup would mean that the reactive fluorine atom must lie well away from this carbon atom Tryptophanase and tyrosine phenol-lyase have been purified by affinity 28

F. Riva, A. Giartosio, C. Borri Valtattorni, A. Orlacchio, and C. Turano, Biochem. Biophys. Res. Comm., 1975,66, 863.

Phosphates and Phosphonates of Biochemical Interest

137

chromatography, using pyridoxal 5’-phosphate immobilized through the 3-oxygen atom.as A two-component resonance signal has been observed when pyridoxal 5’phosphate was added to phosphorylase The resonance changes dramatically on the addition of the activator AMP or the inhibitor glucose 6-phosphate. If the twocomponent signal is due to a slow interchange between two enzymic conformations, then the addition of a ligand probably fixes the enzyme in one of these conformations. Thiamine Phosphates.-Thiamine thiazolone and thiothiazolone have been phosphorylated in two steps to the corresponding diphosphates (8; X = 0 or S).31

These diphosphates bind very tightly to pyruvate dehydrogenase, which is consistent with the suggestion32that they are transition-state analogues of thiamine pyrophosphate. Complexes formed between magnesium ions and thiamine pyrophosphate may be directly involved in enzymic reactions, and such metal complexes have been studied using paramagnetic manganese(@ions.33* 34 The thiamine pyrophosphate in these complexes exists in a folded conformation at low pH, and as the pH is raised the population of unfolded complex increases, presumably due to the ionization of the pyrophosphate group.

3 Sugar Phosphates The stereospecific synthesis of 1,2-truns-glycosyl phosphates from the reaction between dibenzyl phosphate and the 1,2-0rthoesters of protected gluco-, glacto-, and manno-pyranoses, e.g. (9), has been reported (see Scheme 2).36Removal of the protecting groups gives the 1-glycosyl phosphates in high yield. 3-Deoxy-arubino-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36The synthesis takes place at room temperature and neutral pH 29

30 31 32 33 34

35

36

S. Ikeda, H. Hara, S. Sugimoto, and S. Fukui, F.E.B.S. Letters, 1975, 56, 307. S. J. W. Busby, D. G. Gadian, G. K. Radda, R. E. Richards, and P. J. Seely, F.E.B.S. Letters, 1975, 55, 14. J. A. Gutowski and G. E. Lienhard, J. Biol. Chem., 1976, 251, 2863. G. E. Lienhard, Science, 1973, 180, 149. A. A. Gallo and H. 2.Sable, J . Biol. Chem., 1975, 250, 4986. H. J. Grande, R. L. Houghton, and C. Veeger, European J . Biochem., 1973, 37, 563. L. L. Danilov, L. V. Volkova, and R. P. Evstigneeva, Zhur. obshchei Khim., 1975, 45, 2307 (Chem. Abs., 1976, 84, 105 919); L. L. Danilov, L. V. Volkova, V. A. Bondarenko, and R. P. Evstigneeva, Bioorg. Khim., 1975, 1, 905 (Chem. Abs., 1976, 84, 105 921). K. M. Herrmann and M. D . Poling, J. Biol. Chem., 1975, 250, 6817.

Orgaiiophosphorrrs Chemistry

138

j-j"

*

HO

OH

Me (9) Reagents : i, (PhCH,O),POOH; ii, H,-Pd; iii, hydrolyse

Scheme 2

in the presence of CoII ions, but is not stereospecific at C-4, as both the arabino- and ribo-epimers of (10) are formed. The epimers can, however, easily be separated by chromatography. A 3-deoxyoctulosonic acid 5-phosphate (12) is released from the CHO

YO2H

endotoxin of Bordetella pertussis following acid h y d r ~ l y s i s The . ~ ~ gross structure of (12) was established by degradation, and it was assumed that it was the manno-epimer acid 8-pho~phate.~~ by analogy with the known 3-deoxy-~-manno-octu~osonic An analogue (13) of fructose 1,6-bisphosphate in which the phosphate group on C-6 has been replaced by a phosphonomethyl group has been prepared from the correspondingly substituted 3-phosphoglycerate,using a l d ~ l a s eAlthough .~~ (13) is a substrate for aldolase, which is used in its synthesis, it is not a substrate for fructose 1,6-bisphosphatase,Chemical hydrolysis of (13) gives 6-deoxy-6-(phosphonomethyl)D-fructose (14), which is a substrate for glucose 6-phosphate isomerase and a number of other enzymes. Fructose can be sulphurylated with pyridinesulphur trioxide to fructose 6-sulphate. This can be converted by phosphofructokinase into fructose 37 38 39

R. Chaby and L. Szab6, European J . Biochem., 1975, 59, 277. D. H. Levin and E. Racker, J. Biol. Chem., 1959, 234, 2532. D. Webster, W. R. Jondorf, and H. B. F. Dixon, Biochem. J., 1976, 155, 433.

139

Phosphates and Phosphoriatcs of Biochemical Interest

OH

(13)

OH

(14)

1-phosphate 6-sulphate, which is a substrate for both aldolase anc fructose 1,6bispho~phatase.~~ The anomeric composition of (15) as determined by 31Pn.m.r. was 20 %a and 80 %B, a value which corresponds closely to that obtained by 13Cn.m.r. for fructose 1,6-bi~phosphate.~~ The enthalpies of hydrolysis of glycoside cyclic phosphodiesters have been measured42 by flow microcalorimetry, using a phosphohydrolase from Enterobacter a e r ~ g e n e sas ~ ~catalyst. This phosphohydrolase can hydrolyse a wide variety of phosphodiesters, which enables the enthalpies of hydrolysis of glycoside cyclic phosphodiesters to be compared with those of acyclic and monocyclic phosphodiesters. It was that the phosphohydrolase cleaves the 3’- and 5’-ester bonds with similar enthalpies, which are less negative (- 11.1 f 0.2 kcal mol-l) than the value (- 13.2 k 0.4kcal mol-l) that had been reported previou~ly.~~ A number of new nucleoside diphosphate sugars have been synthesized recently, including UDP- and GDP-2-deoxy-~-glucose,~~ uridine-5’-(5-thio-a-~-glucopyranosyl pyr~phosphate)~~ and UDPGlc derivatives in which the pyrimidine ring has been substituted in the 5-position (16).47The size of the substituent X has a marked influence on the efficiency of (16) to be substrates for UDPGlc-dehydrogenase, and analogues in which X had a van der Waals radius of greater than 2 A showed a decreased affinity for the enzyme.47A spin-labelled analogue (17) of a nucleoside diphosphate sugar has been synthesized by the phosphoromorpholidate route from 2,2,6,6-tetramethyl-4-phosphopiperidinyl-l-oxyl and is a potent inhibitor of bovine galact~syltransferase.~~ A Scatchard plot from e.s.r. data indicates that only one 40

41 42 43 44

45 46

47 48

T. M. Martensen and T. E. Mansour, Biochem. Biophys. Res. Comm., 1976, 69, 844. T. A. W. Koerner, L. W. Cary, N. S. Bhacca, and E. S. Younathan, Biochem. Biophys. Res. Comm., 1973,51, 543. J. A. Gerlt, F. H. Westheimer, and J. M. Sturtevant, J. Biol. Chem., 1975, 250, 5059. J. A. Gerlt and G. J. R. Whitman, J. Biol. Chem., 1975, 250, 5053. P. Grcengard, S. A. Rudolph, and J. M. Sturtevant, J. Biol. Chem., 1969, 244, 4798. R. T. Schwarz and M. F. G. Schmidt, European J. Biochem., 1976, 62, 181. T. L. Graham and R. L. Whistler, Biochemistry, 1976, 15, 1189. V. N. Shibaev, G. 1. Eliseeva, and N. K. Kochetkov, Biochim, Biophys, Actu, 1975, 403, 9. L. J. Berliner and S. S. Wong, Biochemistry, 1975, 14, 4977.

Organophosphorus Cheniistry

140

HO OH (16) R = 0-D-glucopyranosyl-1 (17) R = 2,2,6,6-tetramethylpiperidinyl-l-oxyl-4;X = I1

molecule of (17) binds per molecule of A-protein, and kinetic data suggest that the binding of (17) is through the uridine moiety rather than through the sugar. One of the earliest stages in the biosynthesis of bacterial cell-wall peptidoglycan is the transfer of the enol phosphate residue of phosphoenol pyruvate (PEP) to the oxygen attached to C-3’ of the glucosamine moiety of UDPGlcNAc. Inorganic phosphate is liberated and the double bond of the enol pyruvate is preserved. A covalent enzyme-PEP intermediate has been isolated from Enterobacter cloacae which participates in peptidoglycan synthesis, as it will transfer the en01 pyruvate group to the 3’-hydroxy-group of enzyme-bound U D P G ~ C N A CDuring .~~ the transfer of the enolpyruvate moiety, an intermediate (1 8) is formed with a freely rotating methyl group, and the rotation of this group is unrestricted by the enzyme. (2)-Phosphoenol-a-ketobutyrate,which is an analogue of PEP containing an extra methyl group, can be obtained by the enolase-catalysedisomerization of 2-phosphobut-3-enoic acids0and is a substrate for the transferase. This is confirmatory evidence for there being little steric constraint on the methyl group in (18).

BH

YH

H 4Q

50

R. I. Zemell and R. A. Anwar, J. Biol. Chem., 1975, 250, 4959. J. Appelbaum and J. Stubbe, Biochemistry, 1975, 14, 3908.

Phosphates and Phosphonates of Biochemical Interest

141

4 Phospholipids Polyisoprenyl p-D-mannopyranosyl phosphate (19)y51 rather than the a-anomer, may be the naturally occurring compound in calf pancreas.52Citronellol or dolichol were coupled with 2,3,4,6-tetra-O-acetyl-~-~-rnannopyranosyl phosphate with the aid of tri-isopropylbenzenesulphonylchloride to give (19) after deacetylation and purifica0 CH,OII

I/

(19)

tion.61 The configuration of naturally occurring (19) was inferred from hydrolysis with alkali and an a-mannosidase. Since the latter did not cleave either the /3-anomer or (19) or the natural compound, the configuration of the latter could be deduced.52 A mannosyl 1-phosphorylpolyisoprenol has also been shown to be an intermediate in glycoprotein in Neurospora c r a ~ s a . ~ ~ In the crystalline state CDP-choline is highly folded, with the choline residue lying over the pyrimidine ring.54The cytosine is in the anti-conformation relative to the sugar both in CDP-choline and in CDP itself. Cytidine diphospho-sn-1,2diacylglycerol which has been attached to a support through the sugar residue of the nucleotide has been used for the purification by affinity chromatography of 3-snphosphatidyl-1’-sn-glycero-3’-phosphate synthase from bacteria.65 The cell walls of most Gram-positive bacteria contain (1 +3) poly(glycero1 phosphate) teichoic acids which can bear D-alanyl or glycosyl substit~ents.~~ However, the cell walls of Bacillus stearothermophilusB65 contain a glycerol teichoic acid which is free of sub~tituents.~~ This is contrary to evidence that had been obtained from biosynthetic D-Glucose 6-phosphate is converted enzymically into L-myu-inositol 1-phosphate (20) in a process which requires NADf. The base-catalysed cyclization of D-XJJZOhexos-5-ulose 6-phosphate (21), followed by reduction with borohydride, leads to (20) and epi-inositol 3-phosphate (22) (Scheme 3).59This has been put forward as a chemical model for the enzymic synthesis. The phosphorylation of inositols with polyphosphoric acid has been described and the p&’s of inositol hexaphosphate have been determined by 31Pn.m.r.61 51 52

53 54

55 56 57 58 59

6o

61

C. D. Warren, I. Y. Liu, A. Herscovics, and R. W. Jeanloz, J. Biol. Chem., 1975, 250, 8069. A. Herscovics, C. D. Warren, and R. W. Jeanloz, J. Biol. Chem., 1975, 250, 8079. M. H. Gold and H. J. Hahn, Biochemistry, 1976, 15, 1808. M. A. Viswamitra, T. P. Seshadri, M. L. Post, and 0. Kennard, Nature, 1975, 258, 497. T. J. Larson, T. Hirabayashi, and W. Dowhan, Biochemistry, 1976, 15, 974. H. Hussey and J. Baddiley, ‘The Enzymes of Biological Membranes’, ed. A. Martonosi, Plenum Press, New York, 1976, Vol. 2, p. 227. A. J. Anderson and A. R. Archibald, Biochem. J., 1975, 149, 115. L. D. Kennedy, Biochem. J., 1974, 138,525. D. E. Kiely and W. R. Sherman, J. Amer. Chem. SOC.,1975, 97, 6810. D. J. Cosgrove, Carbohydrate Res., 1975, 40, 380. A. J. R. Costello, T. Glonek, and T. C. Myers, Carbohydrate Res., 1976, 46, 159.

Orpnophosphori~sChemistry

142 CHO

1 I HO-C-H I H-C-OH i c=o 1 H-C-OH

H? i, ii

HO HO

~

OH HO

CHZO~,zE,

(21) Reagents : i, 1 M-NaOH; ii, NaBH,

Scheme 3

The 31Pn.m.r. of phospholipids has been the subject of a number of paper^.^^-^^ These have been primarily aimed at investigating the conformation and motion of phospholipids in bilayers, but information has also been obtained on gel-to-liquid crystal transformations of phospholipid^.^^-^ A P31{'H} nuclear Overhauser effect indicates that there is little tendency for mixed phosphatidylcholine/phosphatidylethanolamine vesicles to segregate in separate domains.6s,6 9 A phosphonium analogue (23) of choline chloride has been prepared and converted chemically into

the phosphorylcholine, CDP-choline, and phosphatidylcholine derivatives.70 These derivatives were incorporated into the lipid fractions of rats, and may be useful probes in 31Pinvestigations of phospholipids. 5 Phosphonates

A new synthesis (Scheme 4) of 2-aminoethylphosphonic acid (24) has been described in which bis(dimethy1amino) phosphorochloridate is condensed with an cr-anion derived from an aliphatic nitrile.'l An advantage of this synthesis is that the intermediate (25) can be alkylated, which constitutes the simplest synthesis so far published for substituted aminoethylphosphonicacids. Both C-3 and the phosphorus atom of PEP are incorporated into (24) in Tetrahymena pyri$~orrnis,~~ which confirms 62 63

64 65 66

67 68

70

'1

R. G. Griffin, J . Amer. Chem. Soc., 1976, 98, 851. S. J. Kohler and M. P. Klein, Biochemistry, 1976, 15, 967. H. U. Gally, W. Niederberger, and J. Seelig, Biochemistry, 1975, 14, 3647. B. de Kruijff, P. R. Cullis, and G. K. Radda, Biochim. Biophys. Acta, 1975, 406, 6. P. R. Cullis and B. de Kruijff, Biochim. Biophys. Acra, 1976, 436, 523. W. Niederberger and J. Seelig, J . Amer. Chem. SOC.,1976, 98, 3704. P. L. Yeagle, W. C. Hutton, C.-H. Huang, and R. B. Martin, Proc. Nut. Acad. Sci., U.S.A., 1975,72, 3477. P. L. Yeagle, W. C. Hutton, C.-H. Huang, and R. B. Martin, Biochemistry, 1976,15, 2121. R. G. Edwards and A. R. Hands, Biochim. Biophys. Acta, 1976, 431, 303. J. Blanchard, N. Collignon, P. Savignac, and H. Normant, Tetrahedron, 1976, 32, 455. M. Horiguchi and H. Rosenburg, Biochim. Biophys. Acta, 1975, 404, 333.

Phosphates and Phosphonates of Biochemical Interest

143

0 (Me,N),POCL

'liii

* \I1/PC&C&&H,

0

II (Me,N), PCHRCN

O

-0

II

(Me,N),PC&CN

0

-0 iiy

iii :

\I1 PCHRCH,&H, /

HO' Reagents: i, LiCH,CN; ii, H,-Ni; iii, 6M-HC1; iv, Bu,NOH-RI

Scheme 4

an earlier hypothesis that the biosynthesis of (24) involves an intramolecular rearrangement of PEP. 73 The unstable 3-phosphonopyruvate (26) is a likely intermediate in this biosynthesis but was not isolated from Tetruhyrnena. 2-Amino-3phosphonopyruvate, the next stage in the biosynthesis, was, however, identified as its 2,4-dinitrophenylhydrazone.

6 Oxidative Phosphorylation The chemi-osmotic theory of oxidative phosphorylation has been reviewed,74 a model for mitochondrial oxidative phosphorylation in which a membrane potential or proton gradient might transmit energy from an oxidation step to ATP synthesis has been and adenine nucleotide transport in mitochondria has been reviewed. 13 In a chemical model for oxidative phosphorylation 7 7 the anaerobic oxidation of N-benzyl lY4-dihydronicotinamideby a pyridine solution of haemin was accompanied by the synthesis of ATP from ADP and inorganic phosphate. In support of an alternative chemical model involving sulphenyl phosphates as the reactive species, lipophilic thioureas have been shown to inhibit mitochondria1 oxidative phos73 74 75

76 77 78

W.A. Warren, Biochim. Biophys. Acta, 1968, 156, 340. P. Mitchell, Biochem. SOC.Trans., 1976, 4, 399. P. D. Boyer, F.E.B.S. Letters, 1975, 58, 1; P. D. Boyer, B. 0. Stokes, R. G. Wolcott, and C. Degani, Fed. Proc., 1975, 34, 1711. P. V. Vignais, Biochim. Biophys. Acta, 1976, 456, 1. A. Ohno, T.Kimura, S. Oka, Y. Ohnishi, and M. Kagami, Tetrahedron Letters, 1975, 2371. T. Wieland and E. Bauerlein, Angew. Chem. Internut. Edn., 1968, 7, 893.

144

Organophosphorus Chemistry

p h ~ r y l a t i o n Mixed . ~ ~ disulphides would be formed in the reaction between a sulphenyl phosphate and a thiourea, which would prevent phosphoryl transfer to ADP. Sulphydryl groups have also been implicated in photosynthetic phosphorylation.80

7 Enzymology Enzyme Mechanisms.-The inert co-ordination complex of CrIII and inorganic pyrophosphate binds strongly to yeast inorganic pyrophosphatase, but is not hydrolysed by the enzyme.81Moreover, this complex does not inhibit the MgIIcatalysed hydrolysis of inorganic pyrophosphate by the enzyme. In contrast, the calcium inorganic pyrophosphate complex is a strong inhibitor of the MgII-catalysed hydrolysis although it is not itself a substrate. This probably means that the CrIII-PPi complex binds to the enzyme via the metal ion rather than through the phosphoryl oxygen atoms. The MgII-catalysed hydrolysis of inorganic pyrophosphate by inorganic pyrophosphatase at pH 7 shows a kinetic solvent isotope effect of 1.45.s2 At least one molecule of water must, therefore, be involved in the transition state of this reaction. Alkaline phosphatase from both prokaryotes and eukaryotes contains a specific serine residue which is phosphorylated during the hydrolysis reaction by noncovalently bound inorganic phosphate.83 The native enzyme requires zinc for activity, but a CdII enzyme can be prepared which on treatment with chelating agents gives an apophosphoryl enzyme. On dialysis of the latter with 32P-labelledphosphate, the phosphoryl enzyme is obtained which contains both covalently and non-covalently bound p h o ~ p h o r u s The . ~ ~ two forms of phosphorus can be distinguished by 31P n.m.r. in the native zinc-containing 8 G The chemical shift of the covalently bound phosphorus cannot be related to that of any known amino-acid analogue, e.g. phosphoserine,8sand it is postulated that the anomalous chemical shift is caused by steric strain with an 0-P-0 angle of under 100". This highly strained intermediate, together with a conformation change caused on binding a MgII ion to the zincenzyme,87may be important features in the hydrolytic reaction (Scheme 5). Phosphoglucoisomerase catalyses the interconversion of glucose 6-phosphate and fructose 6-phosphate via enzyme-bound metastable intermediates (Scheme 6). A stable analogue (28) of the enediol intermediate (27), which has been prepared by the aerial oxidation of fructose 6-phosphate,is the strongest known competitive inhibitor of the enzyme.88 Neutral sugar phosphates, e.g. erythrose 4-phosphate (1 1) or glucitol 6-phosphate, are not inhibitors of phosphoglucoisomerase.8gAlthough (1 1) does bind tightly to the enzyme, the binding does not involve a group on the enzyme which is ionizable at physiological pH, as the binding is invariant in the range E. Bauerlein and R. Keihl, F.E.B.S. Letters, 1976, 61, 68. R. H. Vallejos and C. S. Andreo, F.E.B.S. Letters, 1976, 61, 95. 81 J. W. Sperow and L. G . Butler, J. Biol. Chem., 1976, 251, 2611. 8 2 L. M. Konsowitz and B. S. Cooperman, J . Amer. Chem. SOC.,1976,98, 1993. g 3 T. W. Reid and I. B. Wilson, 'The Enzymes', ed. P. D. Boyer, 3rd edn., Academic Press, New York, 1971, Vol. 4, p. 373. a4 J. F. Chlebowski and J. E. Coleman, J. Biol. Chem., 1976, 251, 1202. 8 5 J. F. Chlebowski, I. M. Armitage, P. P. Tusa, and J. E. Coleman, J . Biol. Cliem., 1976,251,1207. s 6 J. L. Block and B. Sheard, Biochem. Biophys. Res. Comm., 1975, 66, 24. 87 J. Ahlers, Biochem. J., 1975, 149, 535. 88 J. M. Chirgwin and E. A. Noltmann, J. Biol. Cfiem., 1975, 250, 7272. 8 9 J. M. Chirgwin, T. F. Parsons, and E. A. Noltmann, J . Biol. Cfzem., 1975, 250, 7277.

'9

80

Phosphates and Phosphonates of Biochemical Interest H

H’

Ser

CH,

Scheme 5 Dglucopyranose 6-phosphate

D-fructofuranose 6-phosphate

Q ~ ~ O - D ~ ~ U6-phosphate CCW

__L

keto-D-fructose 6-phosphate

Scheme 6

HO

145

146

Organophosphorus Chemistry

pH 6-9. A model for the active site of phosphoglucoisomerasehas been proposed from the known crystal structure of the enzyme. The enediolate is believed to hydrogen-bond strongly to a glutamate residue in the active site. Phosphoribosylpyrophosphate(PRPP) synthetase is one of the very few enzymes which transfer a pyrophosphoryl group from ATP in one step. When the synthesis is carried out in lsO-enrichedwater, l80is incorporated into the PRPP, but not into AMP.g1The lSOin the PRPP arises from a pre-exchange between the H,180 and the ribose phosphate, and hence the results confirm that fission of the p-P-0 bond takes place. PRPP and ATP are starting materials in the biosynthesis of histidine, and Nl-(5’-phospho-~-ribosyl)adenosinetriphosphate (29) is an intermediate. The

NH

II

HO

\OH

HO

OH

(29) several

Histidine

ribosyl-N-1 bond has recently been shown to have the p-configuration, and so the bond was probably formed in a single displacement reaction, with inversion of configuration at C-1 of the PRPP.92 Miscellaneous Enzymes.-Derivatives of 1,3,2-dioxaphosphorinan 2-oxide (30) are

X = F,Cl, -0

NO,,or --SCH$QNEt,

very much less effective anticholinesterase agents than alicyclic compounds such as DFP. Recent kinetic investigations show that there is a slow association between the enzyme and (30), which is followed by a slow phosphorylation step to give a stable phosphorylated derivative of the enzyme.g3It is more likely that these two consecutive slow reactions account for the low reactivity of (30) rather than a rapid dephosphorylation of the cholinesterase, as has been suggested by some 91 92

93

P. J. Shaw and H. Muirhead, F.E.B.S. Letters, 1976, 65, 50. G . A. Miller, jun., S. Rosenzweig, and R. L. Switzer, Arch. Biochem. Biophys., 1975, 171, 732. D. Chelsky and S. M. Parsons, J . Biol. Chem., 1975,250, 5669. D. B. Coult, Biochem. J., 1976, 155, 717. Y. Ashani, S. L. Snyder, and I. B. Wilson, Biochemistry, 1972, 11, 3518.

Phosphates and Phosphonates of Biochemical Interest

147

3-Bromo-l,4-dihydroxybutan-2-one 1,4-bisphosphate(31) has been prepared from the protected bromohydrin of cis-but-Zene-l,4-diol.95 Nucleophiles rapidly displace bromide ion from (31), and the latter has been used as an affinitylabel for ribulosebisphosphate carboxylase. In this case two sites are labelled in each enzyme molecule, the two molecules of (31) being linked to the enzyme by two different lysine residuesB6

H-~--B~

(31)

(32) X = CIorF

1-Fluoro-3-hydroxyacetone3-phosphate (32) has been prepared by the oxidation of 1-fluoro-3-chloropropan-2-ol to 1-fluoro-3-chloroacetone followed by treatment of the latter with silver dibenzyl phosphate and catalytic hydr~genation.~' Glycerol 3-phosphate dehydrogenase will reduce (32) to 1-deoxy-1-fluoroglycerol3-phosphate and (32) is also a weak irreversible inhibitor of triose phosphate isomerase. Phosphoproteins.-A chemical synthesis of partially and fully phosphorylated protamines has been described during the past year,98and structural requirements for the enzymatic phosphorylation of phosvitin have been delineated. Phosphorylated forms of phosphofructokinaselOO and fatty acid SynthetaselOl have been discovered recently; both may be concerned with the regulation of their respective enzymes. The ferrate anion in the oxidizing agent potassium ferrate (K,FeO,) is tetrahedral, with a Fe-0 bond length slightly longer than the P-0 bond length in orthophosphate.lo2 Ferrate ion is negatively charged at neutral pH and ferrate has been suggested as an atfinity label for phosphate-binding sites in enzymes. Incubation of phosphorylase b with potassium ferrate inactivates the enzyme and abolishes its ability to bind AMP.lo3 8 Other Compounds of Biochemical Interest Prenyl transferase, which catalyses the addition of an allylic pyrophosphate to isopentenyl pyrophosphate, also catalyses the hydrolysis of geranyl pyrophosphate.lo4 Inorganic pyrophosphate stimulates this hydrolysis, and the C-0 bond is broken in 95 96

97

F. C. Hartman, J. Org. Chem., 1975,40,2638. L. I. Norton, M. H. Welch, and F. C. Hartmann, J. Biol. Chem., 1975, 250, 8062. J. B. Silverman, P. S. Babiarz, K. P. Mahajan, J. Buschek, and T. P. Fondy, Biochemistry, 1975,14,2252.

L. Willmitzer and K. G. Wagner, European J. Biochem., 1975, 59, 43. g9 L. A. Pinna, A. Donella, G. Clari, and V. Moret, Biochim. Biophys. Acta, 1975, 397, 519. looH. W. Hofer and M. Furst, F.E.B.S. Letters, 1976, 62, 118. lol A. A. Qureshi, R. A. Jenik, M. Kim, F. A. Lornitzo, and J. W. Porter, Biochem. Biophys. Res. Comm., 1975, 66, 344. loa R. J. Audette, J. W. Quail, W. H. Black, and B. E. Robertson,J. Solid State Chem., 1973,8,43. lo3 Y. M. Lee and W. F. Benisek, J. Biol. Chem., 1976, 251, 1553. l o 4 C. D. Poulter and H. C. Rilling, Biochemistry, 1976, 15, 1079. g8

148

Organophosphorus Chemistry

the geranyl pyrophosphate, with inversion occurring at C-1 . A mechanism has been proposed for this reaction involving the possible pre-ionization of geranyl pyrophosphate to a carbonium ion. Presqualene pyrophosphate is well established as an intermediate in the biosynthesis of squalene and derived steroids.lo5Terpene phosphonophosphates, e.g. (33), have recently been synthesized and shown to block the biosynthesis of squalene, as the phosphonophosphate group cannot be eliminated under physiological conditions.lo6This is further evidence that presqualene pyrophosphate is an obligatory intermediate in this biosynthetic pathway.

(33) R = geranyl

(34)

A rigorous structural proof of the insecticidal exotoxin (34) from Bacillus thuringiensis has now been published,lo7confirming the a-configuration of the glucosidic bond, The total synthesis of (34) is further confirmation of the correctness of the structural assignment.lO* The exotoxin inhibits RNA synthesis in insects and animals and affects the incorporation of orotic acid into nuclear RNA.lo8 CND0/2 Theoretical calculations have been used to predict the favoured conformations of creatine and creatine derivatives, including phosphocreatine. These calculations predict that phosphocreatine may adopt conformation (35) to avoid unnecessary steric and electrostatic The possibility also exists that creatine kinase phosphorylates creatine stereospecifically to form the favoured conformation (35) at the active site of the enzyme. When chicks are fed a diet containing cyclocreatine (l-carboxymethyl-2-iminoimidazole),the phosphorylated H

I

F. Musco, J. P. Carlson, L. Kuehl, and H. C. Rilling, J . Biol. Chem., 1974, 249, 3746; G. Popjirk, H. Ngan, and W. Agnew, Bioorg. Chem., 1975,4,279. lo6E. J. Corey and R. P. Volante, J . Amer. Chem. SOC.,1976, 98, 1291. 107 M. PrystaS, L. Kalvoda, and F. Sorm, Coll. Czech. Chem. Comm., 1975,40, 1775. l08 L. Kalvoda, M. PrystaS, and F. Sorm, Coll. Czech. Chern. Comm., 1976,41, 788. log A. Cihirk, K. Horska, and K. Sebesta, Coll. Czech. Chem. Comm., 1975, 40, 2912. 110 G. L. Kenyon, G. E. Struve, P. A. Kollman, and T. I. Moder, J . Amer. Chem. SOC.,1976,98, 105

3695.

149

Phosphates aiid Phosphonates of Biochemical Interest

derivative (36) rapidly accumulates in muscle and other tissue.111 It should be noted that (36) cannot adopt a conformation similar to (35) although it is phosphorylated rapidly. Two mechanisms have been proposed for the ATP-dependent enzymic formylation of tetrahydrofolate at N-10. In the first, ATP and formate react initially to generate forrnylphosphate,which is the active formylating species. In the second mechanism, a cyclic phosphorodiamidate (37) is formed in the initial reaction between ATP and ADP + HCOOP0,H-

HCOO- + ATP

HCOOP0,H- + fH4 @ 10-formyl-fH4 f Pi

Mechanism (i)

0-P-N

/ '

01

10-formyl-fH4 + Pi

G=+

lfk '+/,

HN-\ I

-ol \

OOCH

fH4 = tetrahydrofolate

(3 8)

Mechanism (ii)

tetrahydrofolate. Attack on (37) by formate cleaves the phosphorodiamidate to generate (38), which then formylates the N-10 position of the folate. Cyclic NN'diphenyl ethylenephosphorodiamidates (39) are models for (37) and are readily converted into N-formyl derivatives (40)in formate buffers under conditions when the parent diphenyl ethylenediamines are unreactive.l12Recently, in agreement with observations made in the enzymic reaction, it has been shown that an oxygen atom is transferred from formate to orthophosphate during the reaction of formate with (39).I13However, ring opening of asymmetric (39), e.g. X = MeO, Y = C1, results G. R. Griffiths and J. B. Walker, J . Biol. Chem., 1976, 251, 2049. C . Kutzbach and L. Jaenicke, Annalen, 1966, 692, 26. 113 B. A. Amato and S. J. Benkovic, Biochemisfry, 1975, 14,4877

112

6

Organophosphorus Chemistry

150

X = MeO, Y = C1

in the expulsion of the more basic nitrogen, which is contrary to what is found in the natural reaction. Furthermore, l8O is not incorporated into phosphate from solvent water in the enzyme-catalysed reaction. This is contrary to what would be expected if Mechanism (ii) were foIlowed, but is what would occur during Mechanism (i).

8 Nucleotides and Nucleic Acids BY

J. B. HOBBS

1 Introduction Reviewers’ Canute Syndrome - the hallucination that one is about to be drowned beneath a rising tide of reference cards - has become prevalent during the past year, enforcing stringent selection of material covered. The considerable literature dealing with n.m.r. and X-ray studies of nucleotide structure has been omitted; to repair this deficit, the reader is recommended to two books.lS2 Reports of scientific meetings have also been omitted, since the work presented at these generally appears later in full papers in the literature; however, the Meeting Report of the Third Symposium on the Chemistry of Nucleic Acid Components in 19753 can be recommended as a source of interesting papers. 2 Mononucleotides Chemical Synthesis.-Treatment of cyclopropylmethyl alcohol with dibenzyl phosphorochloridate and subsequent hydrogenolysis of the benzyl groups gives cyclopropylmethyl dihydrogen phosphate. The reaction of 2’,3’-isopropylidene ribonucleosides with this compound and DCC affords phosphodiesters of type (l), from which the protecting groups are removed by boiling in dilute acid to give the nucleoside 5’-monophosphates in moderate yield^.^ The method, envisaged as an 0

p-C%-0-P-0

ll

HO 0

0

Me% (1) B = Ade,’Ura, Cua

(2)

alternative to the cyanoethyl phosphate procedure, seems likely to find only limited application. More use is likely to be made of 2-(NN-dimethylamino)-4-nitrophenyl phosphate (2), which on treatment with acetic acid selectively phosphorylates the 1

3 4

‘Structure and Conformation of Nucleic Acids and Protein-Nucleic Acid Interactions’, ed. M. Sundaralingam and S. T. Rao, University Park Press, Baltimore, 1975. W. Guschlbauer, ‘Nucleic Acid Structure’, Springer-Verlag, New York, 1976. Special Publication No. 1, Nucleic Acid Res., 1975. A. M. Schoffstall, J. Org. Chem., 1975, 40, 3444.

151

0rganophosp hor us Chemistry

152

5’-hydroxy-group of unprotected ribonucleosides in fair yields.6 If 3‘-O-acetylthymidylic acid is treated with excess of a bis(alkyl)dithiobis(thioformate) (3) and triphenylphosphine, the alkyl ester (4) of the nucleotide is obtained in high yield without the formation of symmetrical pyrophosphates as by-products.6 The course of reaction envisaged is indicated in Scheme 1. S

S

S

II II RIO-C-S-S-C--OR1

+ Ph,P

--+

(3) 0

0

II

+ Ph,$-O

R20-P-OR1

I

+--

S

I1

II R’O- -C--S--iph, II

R2Q-P-0

-S--C----OR’

‘1 --6PB,

+ ZR’OH +- 2CS,

0-

OH (4)

R’ = Alkyl, Rz = 3’-0-Acetylthyrnidine-5’ Reagents : i, R20P(O)(OH), Scheme 1

Nucleoside 5’-phosphordiamidates may be prepared by treatment of sugarprotected nucleoside 5’-phosphorodichloridates with ammonia. In alkali these break down, regenerating the nucleoside, but in acid, under controlled conditions, one amide group may be removed, and the resulting phosphoramidate used for polyphosphate synthesis. Formation of [2’(N)-+5’]-phosphoramidate links by the reaction of 2’-amino-2’-deoxyuridine with nucleoside 5’-phosphorimidazolates takes place much faster than the formation of [2’(3’) -+5’]-phosphodiester links when a ribonucleoside is employed, and 2’-amino-2’-deoxyuridine-5’-phosphorimidazolate will correspondingly self-condense to form oligomers (5). * The internucleoside phosphoramidate linkage is fairly stable at neutral pH, and the possibility of such oligomers forming templates for abiotic replication may thus be explored.

(6) n = 1-3; B = Ade, C y t , Thy, Gua;

R = H or oligonucleotide chain (5) 5 6

7

*

Y . Taguchi and Y . Mushika, Chem. and Pharm. Bull. (Japan), 1975,23, 1586. H. Takaku, M. Yamana, and Y . Enoki, J. Org. Chem., 1976,41, 1261. A. Simoncsits and J. Tomasz, Nucleic Acid Res., 1975, 2, 1223. R. Lohrmann and L. E. Orgel, J. Mol. Evol., 1976, 7, 253.

Nucleotides and Nucleic Acids

153

When 3’- or 5’-thymidylic acid is treated with 2,4-dinitrofluorobenzenein DMF, the corresponding phosphofluoridates are formed in good yield. Initially the 2,4dinitrophenyl ester of the nucleotide is formed, and the phenate ion subsequently expelled by fluoride ion. If a nucleoside mono-, di-, or tri-phosphate, or an oligonucleotide bearing a free terminal phosphate, is treated with excess mesitoyl chloride in pyridine, the corresponding mesitoyl phosphates (6) are formed,l0 and are reportedly sufficiently stable for work-up of the reaction on DEAE-cellulose. Presumably steric hindrance inhibits hydrolysis. On treatment with appropriate nucleophiles, mesitoic acid is expelled, yielding amides, thioesters, nucleoside polyphosphates, phosphodiesters, or, if hexamethylenediamine-Sepharose is used, immobilized nucleotides. The yields are generally good. It is interesting to note the choice of agent used for phosphorylation at the 5’position, particularly in unprotected nucleosides. Thus, phosphoryl chloride in various trialkyl phosphates has been employed for imidazole nucleosides and 3-deazaguanosine,11for l-methyl-6-thio-inosine,12 for 9-(2,3-0-isopropylidene-a-~lyxopyranosyl)adenine,13 for certain imidazo[1,Zc]pyrimidine ribonucleosidesl4 (albeit in rather low yields), and for arabinonucleosidesl5(although different solvent mixtures have been employed).la Either this reagent, or pyrophosphoryl chloride in acetonitrile, has been used to phosphorylate pyrazolo[3,4-d]pyrimidine nucleosides.17 Enzymatic phosphorylation has been used for 2-amino-6-chloropurine riboand for 3’-amino-3’side,18 for 5-aminouridine,lBfor 2’-arnin0-2’-deoxyadenosine,~~ deoxy-adenosine20and -guanosine.21It is not clear whether the use of enzymes is dictated by the scarcity of the nucleoside or by the need to avoid potential difficulties due to the presence of extra basic amino-groups. However, 8-aminoguanosine has been phosphorylated with phosphoryl chloride and triethyl phosphate.22 In order to study steric and electronic requirements at the C-5’ position of nucleotides with respect to their ability to bind to enzymes, analogues of TMP or TTP (7)23 have been prepared via condensation of 3’-O-acetylthymidine-5’-aldehydewith nitromethane, reduction, acylation at the resulting amino-group, phosphorylation with 2-cyanoethyl phosphate and DCC, and deblocking with ammonia. The phosphonate analogues (8) and (9), isosteres of AMP, are substrates for AMP kinases from rabbit and pig muscle, suggesting that the C(5’)-O(5’) torsion angle of AMP bound to AMP kinase resembles that in the fixed stereochemistry of (8).24 P. W. Johnson, R. von Tigerstrom, and M. Smith, Nucleic Acid Res., 1975, 2, 1945. V. V. Shumyantzeva, N. I. Sokolova, and Z . A. Shabarova, Nucleic Acid Res., 1976, 3, 903. 11 P. D. Cook, R. J. Rousseau, A. M. Mian, P. Dea, R. B. Meyer, jun., and R. K. Robins, J . Amer. Chem. SOC.,1976, 98, 1492. l 2 A. D. Broom and V. Amarnath, Biochem. Biophys. Res. Comm., 1976, 70, 1029. 13 M. Fuertes, J. T. Witkowski, and R. K. Robins, J. Org. Chem., 1975, 40, 2372. 1 4 D . G. Bartholomew, P. Dea, R. K. Robins, and G. R. Revankar, J. Org. Chem., 1975,40,3708. 15 G. R. Revankar, J. H. Huffman, L. B. Allen, R. W. Sidwell, R. K. Robins, and R. L. Tolman, J. Medicin. Chew., 1975, 18, 721. 16 D. C. Baker and T. H. Haskell, J. Medicin. Chem., 1975, 18, 1041. l7 S. M. Hecht, R. B. Frye, D. Werner, T. Fukui, and S. D. Hawrelak, Biochemistry, 1976,15,1005. 18 C . Janion, Acta Biochim. Polon., 1976, 23, 57. W. Hillen and H. G . Gassen, Biochim. Biophys. A d a , 1975, 407, 347. 20 T. H. Fraser and A. Rich, Proc. Nat. Acad. Sci. U.S.A., 1975, 72, 3044. 21 E. Hamel, European J. Biochem., 1976, 63, 431. 2 2 M. Hattori, J. Frazier, and H. T. Miles, Biopolymers, 1975, 14, 2095. 23 F. Kappler and A. Hampton, J. Carbohydrates Nucleosidcs Nliclcotitlr~s,1975, 2 , 109. 24 A. Hampton, F. Kappler, and F. Perini, Bio-organic Chem., 1976, 5, 31. 9

lo

154

Organophosphorus Chenzistry I40

\/

Ho’

LvA HO OH

OH (7)

0

n = lor 3

1

HO

HO OH (9)

(10)

R

1

OH

= Meor Ph

Several useful transformations of the nucleoside moiety in nucleotides have been described. Treatment of CMP with chloroacetone or phenacyl bromide gives the ethenocytidine compounds (lo), which fluoresce strongly in acidic 2-Azidoinosine-5’-monophosphateexists essentially as the cyclized tetrazolo[5,l-b]6-oxopurine nucleotide in equilibrium with a small quantity of the 2-azido-6oxopurine form, and is thus a potentially useful photoaffinity 3’(2’)-0Thiobenzoyl nucleoside 5’-phosphates (1 1) have been prepared by treatment of the monophosphates with thiobenzoylimidazole, with a view to studying thioacyl exchange between the 2’- and 3’-po~itions.~~ Treatment of IMP, GMP, and XMP with silylating agents, followed by addition of ammonia, or primary and secondary amines in the presence of Lewis acids, gives the corresponding N6-substituted adenosine, 2-amino-, or 2-hydroxy-adenosine derivatives, respectively, in good yields.286-Thio-inosine-5’-monophosphatemay be obtained from AMP by direct sulphydrolysis using hydrogen sulphide, or in higher yields via N6-methoxyadenylic acid.29 The reactivities of the bases and phosphate groups of UMP and TMP with methylating and ethylating agents have been studied as a function of pH and the With methylating agents (e.g. diinethyl sulphate) only nature of the alkyl phosphate alkylation is observed below pH 6 , but the proportion of ring alkylation increases with pH above this value. Ethylating agents behave similarly, with less reaction overall, and higher phosphate :base alkylation ratios. 25

26 0-7

28 29

30

N. K. Kochetkov, V. N. Shibaev, A. A. Kost, A. P. Razjivin, and A. Y. Borisov, Nmleic Acid Res., 1976, 3 , 1341. G. Wiegand and R. Kaleja, European J . Biochem., 1976, 65, 473. A. V. Azhayev, A. A. Krayevsky, V. L. Florentiev, M. K. Kukhanova, and B. P. Gottikh, Nucleic Acid Res., 1975, 2 , 1433. H. Vorbriiggen and K. Krolikiewicz, Anrialen, 1976, 745. K. Miura and T. Ueda, Chem. and Phorm. Bull. (Jopnn), 1975, 23, 2064. B. Singer, Biochemistry, 1975, 14, 4 3 5 3 .

Niicleotides and Nitcleic A c i h

155

A complete series of analogues of ApA has been prepared in which one of the adenosine moieties (at either the 3’- or the 5’-end) is replaced by 1-deaza-adenosine or 3-deaza-adenosine, and the internucleotide bond is either (2’+ 5’) or (3’+ 5’).31 Synthesis follows Khorana-style condensation methods. Hyperchromicity studies indicate that, in a pair of positional isomers, the (2’+5’)-isomer is the more heavily stacked. Treatment of 3-deaza-adenosine with its 2’,3’-cyclic phosphate in the presence of ribonuclease M gives the (3’ --f 5’)-dinucleoside monophosphate. Uridylyl(3’+ 5’)-(3-ribosyl-6-methyluracil)has been prepared similarly 32 by treating uridine2’,3’-cyclic phosphate with (12) in the presence of pancreatic ribonuclease. 4Thiouridine, found in tRNA, is readily derivatized, and is thus a useful nucleoside for structural studies. The preparation of a complete series of dinucleoside (2’+5’)and (3’+ 5’)-nonophosphates in which one nucleoside residue is 4-thiouridine and the other adenosine, uridine, or guanosine has been described.33All are generated by sulphydrolysis of the corresponding cytidine compounds with hydrogen sulphide in pyridine. The position of the internucleotidic link is demonstrated by treatment with ribonucleases, which do not split the (2’ -+5’)-isomer. Hyperchromicity is again larger for the (2’ -+ 5’)-isomers. Diribonucleoside monophosphates containing 4thiouridine have also been prepared via phosphotriester methods,34which define a methodology for the construction of oligonucleotides containing this base. If thymidylyl (3’+ 5’)-thymidine is prepared via the ‘phosphotriester method’, using acyl blocking of the sugar hydroxy-groups and a phenyl group to protect the phosphate, it is found that, if sugar hydroxy-groups become free during deblocking before the phenyl group has been removed from the phosphate, transesterification can take place with isomerization, to form (5’-+5’) and (3’-+3’) internucleotide links as well as the desired product. In a careful study, pure thymidylyl-(3’+3’)-, -(3’+5’)-, and -(5’+ 5’)-thymidine have been prepared by phosphotriester methods, by selectively deblocking the acyl groups while leaving the phosphotriester intact, re-masking the hydroxy-groups with the acid-labile 4-methoxytetrahydropyranyl group, alkaline hydrolysis of the phenyl group, and finally treatment with The intermediates, in which the phosphotriester is intact while the sugar hydroxy-groups are free, were

34

Y . Mizuno, S. Kitano, and A. Nomura, Nucleic Acid Res., 1975, 2 , 2193. A. P. Kavunenko and N . S. Sidorova, Nucleic Acid Res., 1976, 3, 1073. M. Keren-Zur, R . Levy, and Y. Lapidot, Nucleic Acid Res., 1975,2, 2289. J. H. van Boom, P. M. J. Burgers, J. den Hartog, and G . van der Marel, Rec. Trau. chin?.,1976,

35

95, 108. A. Myles, W. Hutzenlaub, G. Reitz, and W. Pfleiderer, Cfiem. Ber., 1975, 108, 2857.

32 33

Orgonophosphorits Chemistry

156

subjected to alkaline hydrolysis to determine the degree of i~omerization.~6 By using spleen phosphodiesterase, which cleaves only (3’ -+ 5’)-internucleotide links, and snake venom phosphodiesterase, which splits (3’+ 5’)- and (5‘+ 5’)-links, isomerization can be quantified. Since presumably 3’,5’-cyclophosphate triester intermediates are involved, one is led to wonder why thymidine is not lost. It is presumed that the intermediate must resemble (13), and that on hydrolysis ring-opening, rather than loss of thymidine, is the best way to relieve the steric strain of three equatorial P-0 bonds in the hypothetical transition state. In similar studies in oligoribonucleotide triester synthesis, treatment of (14) under conditions for hydrolysis of the aryl group gave rise to (15), stereoisomeric purity at the phosphorus atom being maintained.37Hydrolysis of each stereoisomer of (15 ) gave rise to

I

I

0 0

0 0

11

H OMe

XOMe

X

(14)

K = 2chlorophenyl. MeThp = 4-methoxytetrahydropyranyl

uridylyl-(3’-+5)- and -(5’+ 5’)-uridine in the same proportions as those obtained by direct hydrolysis of the ‘parent’ stereoisomer of (14), indicating that hydrolysis of phenyl groups occurs mainly, if not exclusively, via (15), and emphasizing the need to block terminal hydroxy-groups of oligonucleotide phosphotriesters with base-stable substituents before deprotection of the internucleotidic link. Phosphotriester methods employing acyl and benzyl groups to block sugar hydroxy-group have been used to prepare a series of benzyl-substituted diuridyl phenyl phosphotriesters in which the internucleotide link is (2’+2’), (3’-+3’), (5’-+5’), (2’+5’) or (3’-+5’).38In 37

H. Rokos, A. Myles, W. Hutzenlaub, and W. Pfleiderer, Chem. Ber., 1975, 108, 2872. J. H. van Boom, P. M. J . Burgers, P. H. van Deursen, J. F. M. de Rooy, and C. B. Reese,

38

J.C.S. Chem. Comm., 1976, 167. G . Reitz and W. Pfleiderer, Chem. Bcr., 1975, 108, 2878.

36

Nucleotides and Nucleic Acids

157

some cases diastereoisomeric pairs were separable, and in others diastereotopic pairs were formed, for analysis by n.m.r. and ~ . d . ~ ~ With a view to preparing electrically neutral systems capable of passage through cell walls, deoxyuridylyl-(3’+5’)-ribonucleoside [P-(2-hydroxyethyl)esters]of type (16) have been prepared by condensation of the base- and sugar-protected dinucleoside monophosphate with monomethoxytrityl ethylene glycol and 2,3,5-tri-isopropyl benzenesulphonyl chloride (2,3,5-TPS), and deblocking with acid.40Compound (16) which is stable at neutral pH, hydrolyses in alkali, in analogy to oligoribonucleotides. Condensation of N6-benzoyl-9-(1’,3’-dihydroxy-2’-propyl)adenine or N s benzoyl-9-(4’-hydroxybutyl)adenine with Ns,2’,3’-O-triacetyladenosine-5’-monophosphate using 2,3,5-TPS reportedly yields triesters (17) 41 and (18) 43 after deblocking with ammonia, although [at least in the case of (17)] it seems possible that intramolecular transesterification could occur, as discussed above. These compounds were synthesized in order to investigate the effects of non-chiral adenosine HO-I

w

P a

Ad e

1

0

€IOCH,CH,O -l’--O

I I

€ I 0 OH .

(16)

B = Ura, Ade,’Gua 0

Ade

\,//”

h

o

R-(-J--P-O.-

It

‘

HO

yo’

(19)

‘ O HO OH H e

Ade

(1 8)

R =

vo.jnde

CH,OH CH,O€I

(a) H ; ( b ) PO,H,; (c) P,O,H,; ( d ) adenosine-3‘;

(e) uridylyL(3‘ + 5’)-adenosine-3’.

analogues on c.d. spectra. Free conformational analogues of nucleotides and oligonucleotides of type (19) have been prepared by successive periodate oxidation and borohydride reduction of appropriate adenosine compounds, in the expectation that, if a normally conformationally rigid enzyme substrate is rendered flexible, it may show stronger binding and inhibitory proper tie^.^^ The ADP analogue is in fact a strong inhibitor of polynucleotide phosphorylase. 30 40

41 42 43

G. Reitz and W. Pfleiderer, Chem. Ber., 1975, 108, 2895. S. N. Mikhailov and J. Srnrt, Coll. Czech. Chem. Comm., 1975, 40, 3739. S. N. Mikhailov and J. Smrt, Coll. Czech. Chem. Comni., 1975, 40, 3080. S. N. Mikhailov and J. Smrt, Coll. Czech, Chem. Comm., 1975, 40, 2191. J. Smrt, S. N. Mikhailov, S. Hynie, and V. L. Florent’ev, Cull. Czech. Chem. Comm.,1975,40, 3399.

Organophosphorus Cheinistry

158

Using phosphotriester methods, dinucleoside (3’ -+5’)-monophosphates containing 6-methyl-2’-deoxyuridine at the 3’- or 5’-end have been prepared.44N.m.r. spectroscopy indicates that this nucleoside possesses the syn conformation in these compounds, and, on treatment with snake venom phosphodiesterase, d(m6UpT) is degraded, while d(Apni6U) is not, indicating that this enzyme, a 3’-exonuclease, requires the anti conformation to be present in the substrate. Two modified nucleoside-5’-monophosphates, (20) and (21), which are resistant to 5’-nucleotidase, have A synthesis of (20) has been been isolated from tRNA snake venom hydroly~ates.~~ reported.* 0

1,

:C:a

0

I/

€10-P-0

1

€10

%

N-

CII,CII,CI INII,

Lo,,,

II

0

]lo-- P---0-

(11

TIL Np NMe,

Hb €I0

011

I 1 0 OIi

Cyclic Nuc1eotides.-A new method for preparation of nucleoside 3’,5’-cyclic phosphates consists of treating the unprotected nucleoside with trichloromethylphosphonyl chloride in triethyl phosphate and ring closure of the resulting nucleoside 5’-trichloromethylphosphonate (22) with potassium t-butoxide to give the required product (23) in high yield.47Fission of the carbon-phosphorus bond takes place, with loss of the trichloromethyl group, and it is thought that a metaphosphate intermediate may be involved. The 3’-amido-analogue of cAMP (24) has been prepared by ring-closure of 3’-amino-3’-deoxyadenosine-5’-monophosphate, using a watersoluble ~arbodi-imide,~~ and the corresponding 5’-thio-3’-amino-analogue (25) has been prepared similarly49 from 3’-amino-5’-thio-3’,5’-dideoxyadenosine-5’-monophosphate, which in turn was obtained by treatment of 3’-amino-5’-bromo-3’,5’dideoxyadenosine with lithium thiophosphate. The 3’-N-benzyl derivative of (24) was also prepared.48 Compound (25) is more stable than (24), exhibiting no hydrolysis at neutral pH, and binding to rabbit-muscle protein kinase one-tenth as strongly as (24). The 1-deaza-adenosine analogue of cAMP has been prepared by ring-closure of l-deaza-adenosine-5’-monophosphate with DCC,50 but this method gave very low yields for the corresponding 3-deaza-compound, and cyclization of the 4-nitrophenyl ester of 3-deaza-adenosine-5’-monophosphatewith potassium t-butoxide was more effective. The same alkoxide has been used to cyclize thymidine 5’-phosphorofluoridate to cTMP in high yield.51 44

45 46 47

48 49 50

51

K. K. Ogilvie and F. H. Hruska, Biochem. Biophys. Res. Coinm., 1976, 68, 375. M. W. Gray, Canad. J . Biochem., 1976, 54, 413. F. Seela and F. Cramer, Chem. Ber., 1976, 109, 82. R. Marumoto, T. Nishimura, and M. Honjo, Chern. andPhnrnt. Bull. (Japnn), 1975,23, 2295. M. Morr, M.-K. Kula, and L. Ernst, Tetrahedron, 1975, 31, 1619. M. Morr, Tetrahedron Letters, 1976, 2127. Y.Mizuno, S . Kitano, and A. Nomura, Chem. and Pharm. Bull. (Japan), 1975, 23, 1664. R. von Tigerstroin, P. Jahnke, and M. Smith, Nucleic Acid Res., 1975, 2 , 1727.

Niicleotides arid Niicleic Acids

159

0

1I 0

(24) .X = 0 (25) .X = S

A daunting number of analogues of CAMP, cIMP, and cGMP with modification at positions 2,5a8,53and 2',54or disubstitution at 1,8;55 2,8;56and 2',8,53e54have been prepared, for the most part by standard transformations of the parent cyclic nucleotides, and investigated for their ability to activate protein kinases and to act as substrates or inhibitors for cyclic nucleotide phosphodiesterase. The relationships between substituent type and ability to activate protein kinase have been examined by multiple regression analysis.52Disubstitution at the 8- and 2'-positions largely abolishes biological 54 Series of 8-n-alkylamino- and 8-n-alkylthioderivatives of cAMP [(26) and (27)] have been examined for their ability to inhibit cAMP hydrolysis by a phosphodiesterase from hog brain cortex.66Inhibition is maximal for the S-octylamino- and 8-hexylthio-derivativesYand it is thought that these represent optimum 'goodness of fit' at the active site of the enzyme. Similar biochemical studies on alkyl phosphotriesters of cAMP have been des~ribed.~' m i t y Chromatography.-A new method of immobilizing ribonucleotides via their cis-diols has been d e s ~ r i b e d The . ~ ~ appropriate ribonucleoside is condensed with ethyl laevulinate, using triethyl orthoformate and an acid catalyst, and the product is phosphorylated, using phosphoryl chloride, and hydrolysed with alkali to give (28). This may then be coupled to aminohexyl-agarose, using a water-soluble carbodiimide. Model studies indicate that coupling takes place via the carboxylate group rather than the phosphate. 52

R. B. Mayer, jun., H. Uno, R. K. Robins, L. N. Simon, and J. P. Miller, Biochemistry, 1975,14, 3315.

53

s4 55 56

57 58

T . A. Khwaja, K. H. Boswell, R. K. Robins, and J. P. Miller, Biochemistry, 1975,14,4238. J. P. Miller, K. H. Boswell, A. M. Mian, R. B. Meyer, jun., R. K. Robins, and T. A. Khwaja, Biochemistry, 1976, 15, 217. H. Uno, R. B. Meyer, jun., D. A. Shuman, R. K. Robins, L. N. Simon, and J. P. Miller, J , Medicin. Chem., 1976, 19, 419. Y. Sasaki, N. Suzuki, T. Sowa, €2. Nozawa, and T. Yokota, Biochemistry, 1976, 15, 1408. R. C. Gillen and J. Nagyvary, Biochem. Biophys. Res. Comm., 1976, 68, 836. F. Seela and S. Waldeck, Nucleic Acid Res., 1975, 2, 2343.

160

0rganophospho rrrs Chemistry

I I

so2

0-P--0

0 0

X CH,CH,CO, H

CH,

RTP

( 2 8 ) B = Ade,Gua

(29) RTP = 1 -ribofuranosyl-5-triphosphate

UDP, dGTP, and uridine-2’(3’),5’-diphosphate have all been linked to Sepharose through the 5’-phosphate moieties, and used for the purification of galactosyl transf e r a ~ and e ~ ~of ribonucleotide reductase,60 and for quantitative affinity chromatography of ribonucleases.61In each case the terminal phosphate is esterified with an amino-alkyl or -aryl moiety which is coupled to cyanogen-bromide-Sepharose.Most affinity columns bearing immobilized adenine nucleotides use attachment via N “(6aminohexyl) substitution on the purine ring.62A new method permits formation of this linkage by treatment of the 6-methylsulphonylpurine nucleotide (29) with aminohexyl-Sepharose.63 Compound (29) is much more reactive than the corresponding 6-chloropurine derivative, and gives high yields of immobilized nucleotides. Coupling via N6-aminocaproyladenosine-5’-triphosphatehas also been described.63

3 Polyphosphates Chemical Synthesis.-Treatment of 2,2,2-tribromoethyl phosphorodichloridate with morpholine yields 2,2,2-tribromoethyl phosphoromorpholinochloridate (30), which phosphorylates Ns-protected adenosine selectively at the 5’-position to form the corresponding phosphoromorpholidate diesters.64 Treatment with a copper-zinc couple removes the tribromoethyl group to give nucleoside 5’-phosphoromorpholidates, ready for conversion into di- and tri-phosphates by the standard method. 0

II Br,CCH,O -P-Cl

I

2

II . HO -P-0-

HO

Y

II P--0-

H0

X

ll

P-0

I

HO I

HO

1

OH

(31) X = S ; Y = 0 ; Z = 0 (32) X = 0 ; Y = S ; Z = 0 (33) x = 0 ;Y = 0 ;z = s L. J. Berliner and S. S. Wong, Biochemistry, 1975, 14, 4977. P. J. Hoffmann and R. L. Blakely, Biochemistry, 1975, 14, 4804. 61 I. M. Chaiken and H. C. Taylor, J. Biol. Chem., 1976, 251, 2044. a2 L. Anderson, H. Jornvall, and K. Mosbach, Analyt. Biochem., 1975,69,401; P. Brodelius and K. Mosbach, ibid., 1976,72, 629; E. Rieke, N. Panitz, A. Eigel, and K. G . Wagner, 2. physiol. Chem., 1975,356, 1177; A. de Flora, A. Moielli, V. Benatti, and F. Giuliano, Arch. Biuchem. Biophys., 1975, 169, 362. 6 3 F. Eckstein, M. Goumet, and R. Wetzel, Nucleic Acid Res., 1975, 2, 1771. 64 J. H. van Boom, R. Crea, W. C. Luyten, and A. B. Vink, Tetrahedron Letters, 1975, 2779. 59

Nucleotides and Nucleic Acids

161

Adenosine 5’40- 1-thiotriphosphate) (31) and adenosine 5’40- 1-thiodiphosphate) may be prepared from adenosine 5’-phosphorothioate using diphenyl phosphorochloridate and inorganic pyrophosphate or phosphate, respectively, and adenosine 5’-(0-2-thiotriphosphate) (32) from adenosine 5’-(0-2-thiodiphosphate)by coupling with 2-cyanoethyl phosphate and DCC and removal of the cyanoethyl group with alkali. Clearly, (31) and (32) exist as stereoisomers, and it is possible to achieve separation of these by the use of kinases which accept, preferentially or exclusively, one stereoisomer as substrate.66 Unfortunately the stereoisomeric pairs are not distinguishable by 31P n.m.r., and can presently only be distinguished by their behaviour with enzymes. Nevertheless, the use of these compounds renders possible the study of stereochemical aspects of enzymic interaction with the polyphosphate chain, and if crystallization and determination of the absolute configuration can be realized, much valuable information will be obtained. Only one isomer of (31) is a substrate for phenylalanyl tRNA synthetase from baker’s yeast,66and it can be shown that, during the exchange reaction of pyrophosphate with this isomer, the stereochemical configuration is retained. As the result of an extensive study in which 18 analogues of ATP were tested for their ability to act as substrates for amino-acyl tRNA synthetases, substrate suitability was thought to depend on the ability to form .~~ speculative a metal-nucleotide complex (34) of acceptable anti c o n f ~ r m a t i o n A model is depicted in Scheme 2.2’-Amino-2’-deoxy- and 3’-amino-3’-deoxyadenosine5’-triphosphate 2o and 2’- and 3’-deoxyadenosine-5’-triphosphate6 8 s 6 g are substrates 0-

,o-P-0 0,

0-

__

H (34)

Scheme 2

for tRNA nucleotidyl transferase from E. coli, allowing the analogues to be introduced as the 3’-terminal residue in tRNA molecules. Examination of the chargeability of these modified tRNAs by amino-acyl tRNA synthetases shows which hydroxy-group in native tRNA is initially amino-acylated by the enzyme. The 2’and 3’-deoxyadenosine 5’-di- and tri-phosphates have been examined as potential 65 66

67 68 69

F. Eckstein and R. S. Goody, Biochemistry, 1976, 15, 1685. F. von der Haar, F. Eckstein, J. Stahl, and F. Cramer, Z . physiol. Chem., 1976, 357, 295. W. Freist, F. von der Haar, M. Sprinzl, and F. Cramer, European J . Biochem., 1976, 64, 389. M. Sprinzl and F. Cramer, Proc. Nut. Acad. Sci. U.S.A., 1975,72, 3049. S. M. Hecht and A. C. Chinault, Proc. Nut. Acad. Sci. U.S.A., 1976, 7 3 , 405.

Organophosphorus Chemistry

162

substrates for mitochondria1 t r a n ~ l o c a s e ,as ~ ~also have (19a) and (19b) 71 and the diand tri-phosphates of adenosine l - o ~ i d e . ~Only * the 3’-deoxyadenosine nucleotides are substrates, the other analogues being thought to be either conformationally unacceptable 7 0 * 71 or of sufficiently different base electronic structure to alter the binding characteristics. 72 When certain transition metals bind to 1,N6-ethenoadenosinenucleotides (33, the fluorescence intensity of the base is quenched, depending on the strength of the metal binding. Since the metal binding depends on the length of the phosphate chain, enzymatic reactions involving phosphate transfer may be monitored by the change in fluorescence quenching so long as the metal-nucleotide complex is a Fluorescence quenching has been used to study the kinetics of [(35)-triphosphate] binding to G - a ~ t i n .The ? ~ depolymerization of F-actin to give G-actin with a number of ATP analogues [(33), (36)-(39)] modified in the triphosphate chain has been

wAd HO

HO OH (35) t~ = 1-3

(36) X ’ = (37) X = (38) X = (39) X =

OH

NH; Y = 0 ; R = H CH,;Y = 0 ; R = H 0;Y = 0 ;R = Me 0 ;Y = CH,; R = H

All analogues effect depolymerization, but only with ATP and (33) is rapid repolymerization seen, with hydrolysis of the triphosphate and incorporation of ADP into F-actin. ATP labelled with l80in the terminal phosphate group is obtained On by incubating [180]H,P0, with ADP and a suitable phosphorylating incubation with myosin subfragment one, some 75% of this label is exchanged within two seconds, thus establishing a rapid, reversible cleavage reaction as an initial step in the interaction of ATP with myosin. On treatment of guanosine with excess pyrophosphoryl chloride, followed by hydrolysis, the 2’,3’-cyclic phosphate-5’-polyphosphates(40) are formed, along with the corresponding 2’(3’)-phosphate and a trace of N3,5’-cycloguanosine-2’,3’-cyclic phosphate, via expulsion of the polyphosphate moiety.77 Compound (41) is the starting point for a synthesis of guanosine-3’,5’-bis-diphosphate(45).78Compound (41) is coupled with S-ethyl dihydrogen phosphorothioate to give (42), which is cleaved by TI ribonuclease to afford (43). Then, (43) is either oxidized with aqueous 70

71

K.-S. Boos and E. Schlimme, 2.physiol. Cltem., 1976, 357, 290. K.4. BOOS,E. Schlimme, D. Bojanovski, and W. Lamprecht, European J. Biochem., 1975,60, 451.

H. H. Mantsch, I. Goia, M. Kezdi, 0. Bgrzu, M. Diinsoreanu, G. Jebeleanu, and N. G . Ty, Biochemistry, 1975, 14, 5593. 7 3 W. E. Hohne and P. Heitmann, Analyt. Biochem., 1975, 69, 607. 74 F. Waechter and J. Engel, European J, Biochem., 1975, 57,453. 75 H. G. Mannherz, H. Brehme, and V. Lamp, European J. Biochem., 1975, 60, 109. 713 C. R. Bagshaw, D. R. Trentham, R. G . Wolcott, and P. D. Boyer, Proc. Nat. Acad. Sci. U.S.A., 72

1975,72, 2592. 77 78

J. Tomasz and A. Simoncsits, J. Carbohydrates Nucleosides Nucleotides, 1975, 2 , 315. A. F. Cook and M. J. Holman, J. Carbohydrates Nucleosides Nucleotides, 1975, 2, 213.

163

Nucleotides and Nucleic Acids

--O--

OH

8

O 'H

(40) R = OH; n , homologous series' . ( 4 1 ) R = OH; n = 0 (42)' R = EtS;, n = 1

iodine to give (44), which is bis-phosphorylated to the required (45) using carbonyldiimidazole, or (43) is monophosphorylated to (46), which is treated simultaneously with iodine and orthophosphate to give (45). The former route afforded a better yield. Compound (45) is produced in bacteria under conditions of amino-acid starvation, and is thought to operate at the transcriptional level in an operonspecific fashion, adjusting the rate of synthesis of ribosomal RNA and tRNA to the availability of amino-acids for protein synthesis. *O The finding that structurally similar adenosine polyphosphates accumulate in Bacillus subtilis starved of a carbon source, during the onset of sporulation, has led to the suggestion that they may cause changes in gene activity,*land thus the control of gene expressionby purine nucleoside polyphosphates may be a general phenomenon. 799

I

+:

HO-P=O

R2

(43) R' .= EtS; R2 = R3 = OH; n, = n, = 1 (44) R' = R2 = R' = OH; n, = n2 = 1 (45) R' = R2 = R3 = OH; n, = n, = 2 (46) R' = EtS; R2 = R3 = OH; n, ' = 1; n, = 2 (47) R' = 2-cyanoethoxy; R2 = OH; = H ; 11, = 1 ; n2 = 0 (48) R' = OH; Rz = EtS; R3 = H; n, = n, = 1 (49) R',= OH; R2 = EtS; R3 = H ; n, = 2; n2 = 1 ( S O ) R' = OH; R2 = EtS; R3 = H; n, = 3 ; n 2 = 1 (51) R' = Rz = OH; R3 = H; n, = 2; n2 = 2 (52) R' = R2 = OH; R3 = H ; n, = 3 ; n, = 2 (53) R' = R' = OH; R' = H ; n, = 2; n2 = I (54) R' = R2 = OH; R' = H ; n, = 3; n, = 1 79 8o

*l

J. C. Stephens, S. W. Artz, and B. N. Ames, Proc. Nat. Acad. Sci. U.S.A., 1975,72,4389. G.Reiness, H.-L. Yang, G. Zubay, and M. Cashel, Proc. Nat. Acad. Sci. U.S.A., 1975,72,2881. H.-J. Rhaese, R. Grade, and H. Dichtelmuller, European J. Biochem., 1976, 64, 205.

164

Organophosphorus Chemistry

Starting with (47) protected at the N2-position, a set of 2’-deoxyguanosine-3’,5’phosphates has been constructed. 82 Coupling (47) with S-ethyl dihydrogen phosphorothioate, followed by treatment with alkali, generates (48). Standard phosphorylation techniques then afford (49) and (50), which on treatment with iodine and orthophosphate yield (51) and (52), with (53) and (54) as by-products. A number of GTP derivatives (55)-(59) containing modified terminal phosphate groups, mostly

I

HO

I

HO

(55) (56) (57) (58) (59)

I Ho

1,-04

Y OH f

HO

= Me0 R = NH,(CH, ),o R = MeCONH(CHJ,O R = PhO R = F

R

prepared by treating GDP with an activating agent and the appropriate monophosphate derivative, have been described.83 All of these guanosine derivatives, along with the guanine-containing equivalents of (19c), (36), (37), 2’- and 3’-deoxyguanohave been sine-5’-triphosphate, and 3’-a.mino-3’-deoxyguanosine-5’-triphosphate, examined for their substrate properties in the partial reactions of protein synthesis catalysed by initiation factor (IF)2 and elongation factors (EF)-Tu and -G from E. Coli.21182-85 The spin label 2,2,6,6-tetramethylpiperidine-l-oxyl has been attached via its 4position to N-6 of AMP 8 6 and to the end-phosphate of UDP,59and these derivatives have been used to study nucleotide binding to phosphorylase b and galactosyltransferase, respectively. D-Xylose is a non-phosphorylatable inhibitor of yeast hexokinase A, and when this sugar and [Mg ATP2-] are incubated with this enzyme, inactivation occurs. A specific serine residue becomes phosphorylated. 2’-Chloro2’-deoxycytidine-5’-diphosphateand 2’-azido-2’-deoxycytidine-5’-diphosphateare specific inhibitors for subunits B1 and B2, respectively, of ribonucleotide reductase from E. coZi.88The former is decomposed to the free base, chloride ion, and 2deoxyribose-5-diphosphate,with concomitant oxidation of enzyme thiols, and the latter stoicheiometrically quenches an organic free radical, causing loss of enzymic activity. Studies on the dephosphorylation of nucleoside 5’-triphosphates catalysed by Mn2+,Ni2+,and Zn2+have been p e r f ~ r r n e dThe . ~ ~ions Mn2+and Ni2+co-ordinate to 8a

83 84

85 86 87

88 89

E. Hamel, E. P. Heimer, and A. L. Nussbaum, Biochemistry, 1975,14, 5055. F. Eckstein, W. Bruns, and A. Parmeggiani, Biochemistry, 1975, 14, 5225. E. Hamel, Biochim. Biophys. Acta, 1975, 414, 326. J. Modolell, T. Girbks, and D. Vdzquez, F.E.B.S. Letters, 1975, 60, 109. S. J. W. Busby, M. A. Hemminga, G. K. Radda, W. E. Trommer, and H. Wenzel, European J . Biochem., 1976, 63, 33. L. C. Menezes and J. Pudles, European J. Biochem., 1976, 65, 41. L. Thelander, B. Larsson, J. Hobbs, and F. Eckstein, J. Biol. Chem., 1976, 251, 1398. P. E. Amsler and H. Sigel, European J. Biochem., 1976,63, 569.

Nucleotides and Nucleic Acids

165

all three phosphate groups, but Zn2+and Cu2+only to the p- and y-phosphates. In the latter cases, a shift of co-ordination to the 01- and p-phosphates and the base moiety is thought to labilize the y-phosphate for dephosphorylation. The nonenzymatic hydrolysis of ATP by polyamines has also been AflGnity Labelling.-Photoaffinity labelling finds ever more adherents. Pancreatic ribonuclease forms stable complexes with its competitive inhibitors uridine- and cytidine-2’(3’),5’-diphosphate, and on irradiation at > 300 nm, using acetone as photosensitizer, covalent attachment occurs to a part of the polypeptide sequence known to lie close to the binding site for pyrimidine nucleotide~.~~ Other photoaffinity labelling experiments have employed azido-derivatives of nucleotides. 8-Azido-adenosine-3’,5’-cyclic phosphate has been used to label CAMPbinding sites in erythrocyte membranes 92 and in protein k i n a ~ e ,and ~ ~ 8-azidoadenosine-5’diphosphate to label a regulatory binding site on glutamate dehydrogenaseg4 and to inhibit adenine nucleotide transport across mitochondrial membranes. However, this last case illustrates an important point, requiring a word of caution: addition of the photoaffinity label after completion of a phosphorylating cycle induced partial oxidation of respiratory pigments, without irradiation. 96 The azido-group is easily reducible and readily takes up free electrons,88and could thus lead to the formation of oxidized artefacts and a reduced nucleotide derivative of unknown properties. Other azido-derivatives of nucleotides used for photolytic labelling include (60) (for mitochondrial F1 ATPase) 96 and (61).97 The latter illustrates the truth that not all 0 HO -P-O

I1

I

‘HO

0

It HOI

-P--O--P-O

0

II

I

HO

72ij””” 0 OH

I

91 92

93 94 95

S. Suzuki and A. Nakahara, Bio-organic Chem., 1975,4, 250. J. Sperling and A. Havron, Biochemistry, 1976, 15, 1489. B. E. Haley, Biochemistry, 1975, 14, 3852. A. H. Pomerantz, S. A. Rudolph, B. E. Haley, and P. Greengard, Biochemistry, 1975,14,3858. R. Koberstein, L. Cobianchi, and H. Sund, F.E.B.S. Letters, 1976, 64, 176. G. Schgfer, E. Schrader, G. Rowohl-Quisthoudt, S. Penades, and M. Rimpler, F.E.B.S. Letters, 1976, 64, 185.

96

97

J. Russell, S. J. Jeng, and R. J. Guillory, Biochem. Biophys. Res. Comm., 1976,70, 1225; S . J. Jeng and R. J. Guillory, J. Supramol. Structure, 1975, 3, 448. V. N. Ankilova, D. G. Knorre, V. V. Kravchenko, 0. I. Lavrik, and G. A. Nevinsky, F.E.B.S. Letters, 1975, 60, 172.

Organophosphorus Chemistry

166 0

N

,

o

N

H

0

-!-II li I

0-P-0--P-0

Q

0

II

0

that’s sticky is a label, for although (61) is a strong competitive inhibitor of ATP binding to phenylalanyl tRNA synthetase, when irradiated, some 20 molecules of analogue could be bound per molecule of enzyme without depressing the enzymic a~tivity.~’ A galling experience for the experimenters, no doubt, and a lesson worth remembering. Treatment of 9-(/3-D-ribofuranosyluronicacid)adenine with diphenylphosphorochloridate and orthophosphate or tripolyphosphate yields (62) and (63), which, although unstable, inhibit rabbit AMP aminohydrolase and pyruvate kinase, respectively, with behaviour characteristic of active-site-specific reagents.gs Adenylate kinases from several sources are inactivated by N6-[2- and .l-fluorobenzoyl]adenosine-5’-triphosphates, with kinetics characteristic of active-site labelling, although these compounds were without effect on yeast hexokinase and rabbit pyruvate k i n a ~ e . ~ ~

0 O-P-

I1

I

HO

(62) n = 1 (63) n = 3

Two aldehydic nucleotide derivatives have found use as affinity labels. The magnesium salt of (64), formed by oxidation of ATP with periodate, is a competitive inhibitor of pyruvate carboxylase with respect to [Mg. ATP2-],100and (65), obtained from the b-anomer of 5-formyluridine-5’-triphosphateon treatment with alkali, is a non-competitive and reversible inhibitor of DNA-dependent RNA polymerase from E. c01i.~O~ In each case, addition of borohydride gives stoicheiometric covalent linkage of the nucleotide to the enzyme, with irreversible inactivation. It is thought that condensation with lysine occurs to give a Schiff’s base intermediate, which undergoes subsequent reduction. 6,6’-Dithio-bis(inosinylimidodiphosphate)(66) forms mixed disulphides between the 6-thiol group of the purine and cysteine residues on myosin; on binding four A. Hampton, P. J. Harper, T. Sasaki, P. Howgate, and R. K. Preston, Biochem. Biophys. Res. Comm., 1975,65, 945. 9 9 A. Hampton and L. A. Slotin, Biochemistry, 1975, 14, 5438. l o o S. B. Easterbrook-Smith,J. C. Wallace, and D. B. Keech, European J. Biochem., 1976,62,125. 101 V. W. Armstrong, H. Sternbach, and F. Eckstein, Biochemistry, 1976, 15, 2086. Q*

167

Nucleotides and Nircleic A rids 0

0

I1 I1 HO-P-0-P-0-P-0 I HO

0

II

CHO (65)

S-

”

HO OH (66)

thiopurine residues, the ATPase activity is lost completely. However, careful work has shown that the non-hydrolysable (36) still binds tightly to 65-80 % of the ATP binding sites of the modified myosin, and it is surmised that (66) is bound to other, possible regulatory, sites, resulting in the observed loss of ATPase activity.lo2This paper is an excellent example of the care with which affinity-labelling results must be examined. A bromoacetylated derivative of the ‘nonsense’ codon UpGpA has been synthesized and used to label ribosomal proteins.lo3 Prebiotic Models.--If AMP, magnesium ions, and trimetaphosphate are mixed and the solution is allowed to evaporate at room temperature, adenosine 5’-polyphosphates are formed in high yield.lo4If the same reaction is performed in water at pH 8.8 for extended periods, there is a tendency to formation of shorter polyphosphate products, notably ATP, and a convincing case can thus be made for ATP formation under ‘primitive earth‘ conditions. If glycine, ATP, and imidazole are heated together in the solid state, glycine oligomers are formed.lo6Reaction is thought to proceed via formation of adenosine 5’-phosphorimidazolateor 5’-glycine phosphoramidate as intermediate, which on reaction with glycine forms an acyl phosphate of type (67) that is suitable for peptide coupling. Imidazole-catalysed transfer of phenylalanine from (67) to poly(rU) has been examined as a model system for tRNA amino-acylation.106 If thymidylic acid is heated with cyanamide at pH 3, oligomers, for the most part cyclic, are formed, presumably via activated phosphate intermediates such as (68).lo7 On addition of acid salts, the same reactions can be realized at neutral pH.lo8 102

P. D. Wagner and R. G. Yount, Biochemistry, 1975, 14, 5156.

1°3 0. Pongs and E. Rossner, 2.physiol. Chem., lo4 R. Lohrmann, J . Mol. Evol., 1975, 6, 237. lo5 H. Sawai, R. Lohrmann, and L. E. Orgel, J.

lo6 107

108

1975,356, 1297.

Mol. Evol., 1975, 6, 165. A. L. Weber and J. C. Lacey, jun., J. Mol. Evol., 1975, 6 , 309. D. G. Odom and J. T. Brady, J, Mol. Evol., 1975, 6 , 199. D. G. Odom, J. T. Brady, and J. Orb, J. Mol. Evol., 1976, 7 , 151.

168

Organophosphorus Chemistry 0

R-CH-C-

II

0

O-P-

I1

NH,

w

-0-7

I

-0

(67) R = H or PhCH,

Ad c

HO OH

0

I II c-0-P-0 II

+NH,

-0

HO (68)

If (3’ -+ 5’)-linked hexa-adenylic acid bearing a 2’,3’-cyclic phosphate at the 3’-end is annealed to a poly(rU) template in the presence of ethylenediamine hydrochloride at pH 8 for extended periods, the dodecamer and octadecamer are formed. Digestion with Taribonuclease reveals that some 95 % of the new links formed are (2’+5’).lU9 If now the dodecamer containing a single (2’+ 5’)-link and an all-(3’+ 5’)-dodecamer are hydrolysed at pH 8 in aqueous ethylenediamine, the rates of hydrolysis are similar, but addition of two equivalents of poly(rU) causes acceleration of the hydrolysis of the former and retardation of hydrolysis of the latter.l1° Indeed, when the oligomers are fully constrained in the helical form, it is estimated that the (2’+5’)-link is hydrolysed at 900 times the rate of the (3’+5’)-link. The poly(rU) is thought to hold the (2’+ 5’) internucleotide bond in a conformation which favours in-line displacement by the 3’-hydroxy-group. While this poses a ‘chicken-and-egg’ problem, it is clear how a selective advantage for the (3’-+5‘) internucleotide bond can thus be propagated. 4 Oligo- and Poly-nucleotides Chemical Synthesis.-Chemical methods in oligonucleotide synthesis have been reviewed.lll In a comparative study of condensing agents used in oligoribonucleotide synthesis, DCC, TPS, and triphenylphosphine-2,2’-dipyridyl disulphidella were found to be the most effective for joining a protected nucleoside 3’-phosphate to the 5’-hydroxy-group of another protected nucleoside residue, and TPS best for performing the same coupling between oligonucleotide b10cks.l~~ The use of triphenyl phosphite and 2,2’-dipyridyl diselenide as a system of condensing and coupling agents has been described.l14 Yields are high, and no side-reactions are observed during coupling. The reagent may also be used to prepare phosphomonoamidates in high yield. A base-catalysed method for synthesis of the internucleotide link consists of treating a nucleoside 3’- or 5’-phosphorofluoridate with a nucleoside bearing a free 5’- or 3’-hydroxy-group in the presence of potassium t-butoxide.61Yields are good if only pyrimidine bases are present, but are not as good when purine derivatives are used.lls An alternative approach to the synthesis of internucleotide bonds is to use an insoluble condensing agent, such as poly(3,5-diethylstyrene)sulphonyl chloride.ll6 A. Usher and A. H. McHale, Science, 1976, 192, 53. D. A. Usher and A. H. McHale, Proc. Nut. Acad. Sci. U.S.A., 1976, 7 3 , 1149. 111 R. I. Zhdanov and S. M. Zhenodarova, Synthesis, 1975,222. 1 1 2 T. Mukaiyama, Angew. Chem. Znternat. Edn., 1976, 15, 94. 113 E. Ohtsuka, T. Sugiyama, and M. Ikehara, Chem. and Pharm. Bull. (Japan), 1975, 23, 2257. 114 H. Takaku, Y. Shimada, Y . Najajima, and T. Hata, Nucleic Acid Res., 1976, 3, 1233. 115 R. von Tigerstrom, P. Jahnke, V. Wylie, and M. Smith, Nucleic Acid Res., 1975, 2 , 1737. 116 M. Rubinstein and A. Patchornik, Tetrahedron, 1975, 31, 1517. logD. 110

Nucleotides and Nucleic Acids

169

After coupling, the reagent is simply filtered off, and potential by-products such as sulphonate esters are also removed. The reaction is thought to involve initial formation of a sulphonate-phosphate anhydride, which then forms symmetrical pyrophosphates and trimetaphosphate triesters for attack by alcohol. While yields are high for dinucleoside phosphates, steric hindrance seems likely to limit this agent’s usefulness. The use of dichlorophosphoric acid for forming phosphodiesters and internucleotide bonds has also been described.l17 Internucleotidic (3’ --f 5’)phosphoramidate links can be formed by direct coupling of a protected nucleoside 3’-phosphate with 5’-amino-5’-deoxynucleoside derivatives, using triphenylphosphine-2,2’-dipyridyl disulphide.ll* If a deoxyribonucleoside 5’-monophosphate is first esterified with a bulky apolar group, and then used as the 5’-terminus for synthesis of an oligodeoxyribonucleotide, reaction products may conveniently be isolated by solvent-extraction techniques, up to about the tetranucleotide stage. 2-(4-Tritylphenyl)thioethanol (69) and 2-(4tritylphenyl)sulphonylethanol(70)have been used for this purpose.110For deblocking, (69) is first oxidized to (70) with N-chlorosuccinimide and then removed with alkali. 0-

(69) X = S (70) X = SO,

Among several new phosphoramidates investigated as potential protecting groups in oligoribonucleotide synthesis, those derived from 4-methylsulphoxylaniline (71) show promise, being stable under conditions in which the monomethoxytrityl group is removed, but cleaved by isoamyl nitrite.lZ0 Pentadecathymidylic acid has been prepared by the ‘triester method’, using alkalilabile protecting groups for internucleotide and 3’-terminal phosphates, and acidlabile protection of the 5’-hydroxy-group, and extending the chain from the 3’towards the 5’-end.la1 As condensing agents for forming internucleotidic links, the arylsulphonyltriazoles (72) and (73),leaprepared from the corresponding sulphonyl chloride and (1H)-l,2,4-triazole, afford high yields, particularly when purine bases are present, and by-products resulting from the sulphonation of hydroxyl and base moieties are much reduced.lz29l z 3Both (72) and (73) have been employed for lengthy oligonucleotide s y n t h e s e ~la4 . ~ Arylsulphonyltetrazoles ~~~ (74), similarly prepared, 11‘ lL9 120 121

M.Rubinstein and A. Patchornik, Tetrahedron, 1975, 31, 2107. G. L. Greene and R. L. Letsinger, Nucleic Acid Res., 1975, 2, 1123. K. L. Agarwal, Y. A. Berlin, H.-J. Fritz, M. J. Gait, D. G. Kleid, R. G. Lees, K. E. Norris, B. Ramamoorthy, and H. G. Khorana, J. Amer. Chem. Suc., 1976,98, 1065. E. Ohtsuka, T. Miyake, and M. Ikehara, Nucleic Acid Res., 1976, 3, 653. K.Itakura, N.Katagiri, C. P. Bahl, R. H. Wightman, and S. A. Narang, J. Amer. Chem. SOC., 1975,97, 7327.

122 123 lZ4

N.Katagiri, K. Itakura, and S. A. Narang, J. Amer. Chem. SOC.,1975, 97, 7332. T. E. England and T. Neilson, Cunud. J. Chem., 1976, 54, 1714. C. P. Bahl, R. Wu, K. Itakura, N. Katagiri, and S. A. Narang, Proc. Nut. Acud. Sci. U.S.A., 1976, 73, 91.

Organophosphorus Chemistry

170

(72) R‘ = H; R2 = NO, (73) R‘ = R2 = Me

(74)

R = H,Me,orMe,CH

also afford high yields in oligonucleotide coupling, reacting faster than the corresponding triazoles, but tend to decompose on storage.126 New agents have been described for insertion of the phosphate group prior to forming the internucleotide link. Treatment of 2-chlorophenyl phosphorodichloridate with one equivalent of 2,2,2-trichloroethanol affords (75), which reacts with 5’protected thymidine to give the 3’-phosphotriester in high yield.126Removal of the trichloroethyl group and subsequent condensation with the 5’-hydroxy-group of another nucleoside residue using TPS generates a protected internucleotide link. If a suitable min e , e.g. cyclohexylamine or morpholine, is used in place of trichloroethanol, the agents (76) are formed, which may be used to prepare nucleoside or oligonucleotide 3’- or 5’-ary1phosphoramidates.l2?Alternatively, treatment of 4chlorophenyl phosphorodichloridate with (1H)-l,2,4-triazole affords bis(triazolyl)4chlorophenyl phosphate (77),122which on successive treatments with a 5’-blocked

base-protected deoxynucleoside and 2-cyanoethanol affords the monoaryl monocyanoethyl nucleoside-3’-phosphotriester,suitable for deprotection and further coupling as described above. Tetrabutylammonium fluoride in THF rapidly removes cyanoethyl, trichloroethyl, and phenyl groups from the internucleotide link under mild conditions,128a valuable finding which may well eliminate the danger of isomerization described previously. The condensed intermediates produced during oligonucleotide synthesis have been studied by adding TPS or DCC to thymidine phosphate derivatives and observing the resulting 31Pn.m.r. If 8-mercaptoadenosine-2’,3’-cyclic phosphate is treated with a phosphateactivating agent, e.g. diphenyl phosphorochloridate or tetraphenyl pyrophosphate, an oligomer is formed in which each phosphate is esterified by the 2’- and 3’hydroxy-groups of one nucleoside residue and the 5’-hydroxy-group of the next. On J. Stawinski, T. Hozumi, and S. A. Narang, Canad J. Chent., 1976, 54, 670. J. H. van Boom, P. M. J. Burgers, and P. H. van Deursen, Tetrahedron Letters, 1976, 869. lz7 J. H. van Boom, P. M. J. Burgers, R. Crea, W. C. M. M. Luyten, A. B. J. Vink, and C. B . Reese, Tetrahedron, 1975, 31,9253. 12* K. K. Ogilvie, S. L. Beaucage, and D. W. Entwistle, Tetrahedron Letters, 1976, 1255. l Z 9D. G. Knorre, A. V. Lebedev, and V. F. Zarytova, Nucleic Acid Res., 1976, 3, 1401. 125

126

171

Nucleotides and Nucleic Acids

heating, ring-closure takes place in the nucleoside residues, affording low yields of (3’+5’)-linked oligomers of 8,2’-,S’-cycloadenylic acid.130 Dinucleoside monophosphates containing this residue at the 5’-end may be prepared similarly. The simplest method for forming oligomers, however, is treating Ns-benzoyl-8,2’-S-cycloadenylic acid with DCC, and the same method has been used to oligomerize 6,2’-anhydro-6hydroxy-auauridylic acid (79).131The octamer of (79) appears to form 1 :1 or 2: 1 complexes with the octamer of (78), depending on the proportions mixed, and c.d. data suggest the formation of left-handed helices in each case.

0

0

II HO-P-0

I/

HO-P-0

HO

HO

HO

HO (78)

B

(79)

H°Cmde HO

(80)

(81) B = Ade (82) B = Ura

Diester methods have been used to synthesize analogues of the initiator codon ApUpG in which the adenine residue has a fixed torsion angle, as for instance in (78),132and triester methods have been used to prepare dinucleoside phosphates and containing the hydroxyalkyl nucleosides 9-(4’-hydroxybuty1)codon analogues adenine (80),9-(3’-hydroxypropy1)adenine (8l), and 1-(3’-hydroxypropyl)uracil(82), with a view to determining the effect of the achiral residues on the c.d. spectra. Enzymatic Synthesis.-The total synthesis by chemical and enzymatic methods of the structural gene for the precursor of a tyrosine suppressor tRNA from E. coli, a DNA duplex that is 126 nucleotides long, has been described. This, Khorana’s Meisterwerk to date, represents the highest state of the art, and proceeds by methods which are already famous, and the touchstone of those who wish to If A(pA), and (pU),, the latter labelled with 32Pat the 5’-end, are incubated with ATP and TpRNA ligase, it is possible to isolate a product in which AMP is joined to the 5’-end of (pU), by a (5’+5’) pyrophosphate link.13sIf this material is incubated 1339

130

M. lkehara and T. Tezuka, Niicleic Acid Res., 1975,2, 1539.

131 S. Uesugi, T. Tezuka, and M. Ikehara, J. Amer. Chem. SOC.,1976, 98, 969. 132 M. Ikehara, T. Nagura, and E. Ohtsuka, Nucleic Acid Res., 1975, 2, 1345.

135

S. N. Mikhailov, V. L. Florent’ev, and J. Smrt, CON.Czech. Chem. Comm., 1975, 40, 3734. S. N. Mikhailov and J. Smrt, Coll. Czech. Chem. Comm., 1975, 40, 2353. H. G. Khorana, K. L. Agarwal, P. Besmer, H. Biichi, M. H. Caruthers, P. J. Cashion, M.

136

Fridkin, E. Jay, K. Kleppe, R. Kleppe, A. Kumar, P. C. Loewen, R. C. Miller, K. Minamoto, A. Panet, U . L. RajBhandary, B. Ramamoorthy, T. Sekija, T. Takeya, and J. H. van de Sande, J. B i d . Chem., 1976, 251, 565 and following papers. E. Ohtsuka, S. Nishikawa, M. Sugiura, and M. Ikehara, Nuckeic Acid RLY., 1976, 3, 1613,

133

134

172

Organophosphorus Chemistry

with A(p& and the enzyme in the absence of ATP, A(pA),(pU), is formed, strongly indicating that the unsymmetricalpyrophosphate is an intermediate in the mechanism of oligonucleotidejoining by this enzyme. When a mixture of dCTP, dGTP, dATP, and 5’-amino-5’-deoxy-TTP is incubated with DNA polymerase I, T4 DNA ligase, and the (+) strand of bacteriophage $X 174 as template, the (-) strand of the duplex circular DNA so formed contains phosphoramidate links,137demonstrable by chain breakage at pH 3.5, as shown by the effect on the sedimentation coefficient. 2’-0-(1-Methoxyethyl)nucleoside-5’-diphosphatesare ‘single addition’ substrates for polynucleotide phosphorylase for the synthesis of oligoribonucleotidesof defined sequence, and optimum conditions for their preparation have been described.138The polymerization of appropriate nucleoside 5’-diphosphates using this enzyme has led to the description of a number of new homopolynucleotides, including poly(7deaza-8-aza-adenylic acid),17 poly(isoguany1ic acid),139 poly(2’-O-ethylcytidylic acid),140 poly(5-aminouridylic acid),lg poly(8-aminoguanylic acid),141 poly(1methyl-6-thioinosinic acid),12 and poly(6-thioinosinic which was obtained from poly(6-chloropurinylic acid) by sulphydrolysis. 6-Thioinosine-5’-diphoshate,^^^ like N6-methoxy-2-aminoadenosine-5’-diphosphate1~ and 7-carboxamido7-deaza-S-a~a-adenosine-5’-diphosphate,~~ would not form a homopolymer but could be copolymerized with a suitable naturally occurring substrate. The polynucleotide analogues have generally been studied for their stacking properties and for the formation of ordered self-structures or complexes with complementary polynucleotides. Other studies have concerned their ability to inactivate~ornplement,l~~9 144 and to inhibit viral reverse t r a n s ~ r i p t a s e s . l ~While ~ - l ~ ~2’-cNoro-2’-deoxyuridine and -cytidine are easily hydrolysed to arabinonucleosides via intermediate 02,2’-cyclonucleosides, this reaction is much slower in the corresponding 5’-nucleotides, and slower still in the polynu~leotides.~~~ It is thought that the negatively charged phosphate groups stabilize the anti conformation, while formation of the cyclonucleoside derivative requires that a syn conformation be adopted. Several new repeating-sequence polydeoxyribonucleotides have been prepared, using combined chemical and enzymatic synthesis.lso Thus, the base-protected oligonucleotidesd(pApGpC) and d(pCpTpG) are synthesized by standard methods, and each is oligomerized using mesitylenesulphonyl chloride, and the bases are then deblocked. The dodecanucleotide tetramers are then hybridized, and used as templates for DNA polymerase I; the polymers thus generated may in turn be used R. L. Letsinger, B. Hapke, G. R. Petersen, and L. B. Dumas, Nucleic Acid Res., 1976,3, 1053. G. N. Bennett and P. T. Gilham, Biochemistry, 1975, 14, 3152. 130 T. Golas, M. Fikus, Z . Kazimierczuk, and D. Shugar, European J . Biochern., 1976, 65, 183. 140 M. Kielanowska and D. Shugar, Nucleic Acid Res., 1976, 3, 817. 1 4 1 M. Hattori, J. Frazier, and H. T. Miles, Biochemistry, 1975, 14, 5033. 142 A. D. Broom, M. E. Uchic, and J. T. Uchic, Biochim. Biophys. Acta, 1976,425, 278. 143 E. de Clercq, P. F. Torrence, J. Hobbs, B. Janik, P. de Somer, and B. Witkop, Biochenz. Biophys. Res. Comm., 1975, 67, 255 144 E. de Clercq, P. F. Torrence, T. Fukui, and M. Ikehara, Nucleic Acid Res., 1976, 3, 1591. 145 E. de Clercq, A. Billiau, M. Hattori, and M. Ikehara, Nucleic Acid Res., 1975, 2 , 2305. 146 G. F. Gerard, P. M. Loewenstein, M. Green, and F. Rottman, Nature, 1975, 256, 140. 1 4 7 R. Mikke, M. Kielanowska, D. Shugar, and B. Zmudzka, Nucleic Acid Res., 1976, 3, 1603. 148 B. I. S . Srivastava, Biochem. Biophys. Acta, 1975, 414, 126. 149 J. Hobbs and F. Eckstein, Nucleic Acid Res., 1975, 2, 1987. 150 R. L. Ratliff, D. E. Hoard, F. N. Hayes, D. A. Smith, and D. M. Gray, Biochemistry, 1976,15, 168.

137

138

Nucleotides and Nricleic Acids

173

as templates for DNA-dependent RNA polymerase. Thus a set of repeatingsequence polynucleotides may be built from only two trinucleotide starting blocks. Starting with poly(dT) and poly(dC), by elegant enzymatic tailoring and the use of deoxynucleotidyl terminal transferase, it is possible to build block duplexes of the form d(CnAm) d(TmGn),151 The drug netropsin binds specifically to the oligo(dA)* oligo(dT) segment of the duplex, and it is found that the co-operative melting temperature is raised not only for this, but also for the oligo(dG).oligo(dC) segment. Similar results are obtained with actinomycin. It has been proposed that the bound drug stabilizes the helix at a point remote from the actual binding site (‘telestability’)lS1,lS2and that this represents a model for gene regulation at a distance. Sequencing.-With the elucidation of the primary and secondary structure of the replicase gene, the complete 3569-nucleotide-long sequence of the RNA of bacteriophage MS2 is now known.ls3This is the first organism for which theentire nucleic acid structure has been elucidated, and Fiers and his group richly deserve their bouquet. If polyribonucleotides are treated simultaneously with methoxylamine and bisulphite, cytidine residues are converted into 5,6-dihydro-N4-methoxycytidine-6sulphonate,ls4and uridine into 5,6-dihydrouridine-6-~ulphonate.~~~ Treatment with dilute ammonia regenerates the uridine residues, leaving the dihydrocytidine derivatives unaffected. When only the cytidine residues have been derivatized, pancreatic ribonuclease becomes ‘uridyl’ ribonuclease, since it is unable to cleave the chain on the 3’-side of the modified cytidine.lS4This allows the isolation of blocks of modified cytidine residues. T2 ribonuclease may also be used. Alternatively, a ribonuclease from Physavurn polycephalum has been found to hydrolyse CpX links very slowly, allowing the isolation of cytidine b10cks.l~~ If both uridine and cytidine residues are modified, T2 ribonuclease acts as ‘puryl’ ribonuclease, allowing the isolation of cumulative blocks of pyrimidines.155This ability to alter the specificity of nuclease cleavage is a useful tool in sequence analysis. Two very powerful new methods for DNA sequencing have been described in the past two years, and are summarized in a review letter.ls7One useful method in DNA sequencing, ‘ribo-sub~titution’,~~~ consists of allowing a complementary piece of DNA to be synthesized (‘repair’ or ‘copy’ synthesis) using DNA polymerase, manganese ion, three deoxynucleoside triphosphates, and one ribonucleoside triphosphate. Digestion with ribonuclease A then gives oligodeoxynucleotideswith a ribonucleotide 3’-terminus, which can then be sequenced by standard methods. Altering the identity of the ribonucleotide gives different oligonucleotide patterns, 150 Copy synthesis methods using DNA 160 and sequence determination is 151

J. F.Burd, J. E. Larson, and R. D. Wells, J. Biol. Chenz., 1975, 250, 6002.

J. F. Burd, R. M. Wartell, J. B. Dodgson, and R. D. Wells, J. Biol. Chem., 1975, 250, 5109. W. Fiers, R. Contreras, F. Duerinck, G. Haegeman, D. Iserentant, J. Merregaert, W. Min Jou, F. Molemans, A. Raeymaekers, A. van den Berghe, G. Volckaert, and M. Ysebaert, Nature, 1976,260, 500. 154 A. M. Mazo, V. S. Scheinker, and L. L. Kisselev, Mol. Biol. Reports, 1975, 2, 233. l55 A. M. Mazo and L. L. Kisselev, F.E.B.S. Letters, 1975, 59, 177. lS6R. Contreras and W. Fiers, Analyt. Biochern., 1975, 67, 319. 157 G. B. Kolata, Science, 1976, 192, 645. 158 K. J. Marians, R. Padmanabhan, and R. Wu, Arch. Biochem. Biophys., 1975,169, 108. l 5 9 J. E.Donelson, B. G. Barrell, H. L. Weith, H. Kossel, and H. Schott, European J . Biochem., 1975, 58, 383. 160 D. G.Kleid, K. L. Agarwal, and H. G. Khorana, J . Biol. Chem., 1975, 250, 5574.

152

153

174

Organophosplzoriis Chemistry

and RNAIG1primers have been used to analyse DNA sequences preceding transcriptional initiation160and following its terrnination,l6l Terminal deoxynucleotidyl transferase normally adds honiopolydeoxynucleotide tails to single-stranded DNA primers in the presence of a deoxynucleoside triphosphate and magnesium. If cobalt is used instead, not only does double-stranded DNA become an acceptable substrate, but ribonucleotides or homopolymer deoxyribonucleotide tracts may be added to all forms of duplex DNA at their 3’-ends, regardless of whether these are staggered or even.lS2This allows terminal labelling for sequence analysis at the cleavage sites of restriction endonucleases,1621 l e 3 or tail formation for in uitro studies on recombinant DNA.162 If RNA or double-stranded DNA containing some 5’-end phosphate groups is incubated with [Y-~~P]ATP and polynucleotide kinase, only those chains lacking a phosphorylated 5’-end are labelled. In the presence of ADP, however, all 5’-ends are labelled, since the ‘cold’ phosphate is exchanged via the reverse reaction of the enzyme. Comparison of the degrees of labelling with and without ADP gives the proportion of chains initially carrying a 5’-phosphate, and this method has been used to show a preference for the formation of 5’- over 3’-monoesters in high-pressure shearing of double-stranded RNA.16*Base analysis of the 3’-ends of breaking sites indicates that irradiation or mechanical breakage occurs randomly in prokaryotic DNA, but there seems to be a slight tendency for mechanical breakage of eukaryotic DNA to occur in thermodynamically less stable regions, possibly at (dA . dT) spacer Sequence analysis of the 5’-ends of viral and nuclear mRNA molecules reveals that these are frequently ‘capped’, with an unusual structure in which 7-methylguanosine is joined by a (5’-+5’) triphosphate link to a 2’-O-methyl nucleoside moiety which is the first residue in the (3’+5’)-linked polynucleotide chain.166-16gThe presence of this ‘cap’ structure is required for ribosomal binding and translation to take 168 and 7-methylguanosine-5’-pliosphate inhibits translation by preventing formation of the ribosome-niRNA complex.169 5 Analytical Techniques and Physical Methods Separation and Quantitation.-The specific radioactivity of [ p 32P]ATP of very high activity (up to 240 Ci per millimole) may be measured by using it to phosphorylate [dT(pT), 0] quantitatively, using polynucleotide kinase, isolating the labelled undecanucleotide, and measuring its activity.170 Isotope dilution is used to confirm the values. An alternative method of measuring specific radioactivities of ribonucleoside triphosphates utilizes a 3M-labellednucleoside triphosphate (e.g. UTP) of unknown specific activity, a 14C-labellednucleoside (e.g. ATP), a suitable primer (in M. Rosenberg, B. de Crombrugghe,and R. MUSSO, Proc. Nut. Acad Sci. U.S.A., 1976,73,717. R. Roychoudhury, E. Jay, and R. Wu, Nucleic Acid Res., 1976, 3, 863. D. E. Garfin, H. W. Boyer, and EI. M. Goodman, Nucfeic Acid Res., 1975, 2 , 1851. l a 4 G. Chaconas, J. H. van de Sande, and R. B. Church, Biochem. Biophys. Res. Comm., 1975,66, 962. l G 5U. Bertazzoni, Biochim. Biophys. Acta, 1975, 395, 239. 1 6 6 K. Shimotohno and K. Miura, F.E.B.S. Letters, 1976, 64, 204. 16’ D. Canaani, M. Revel, and Y . Groner, F.E.B.S. Letters, 1976, 64, 326. 168 G . W. Both, Y. Furuichi, S. Muthukrishnan, and A. J. Shatkin, Cell, 1975, 6, 185. 169 E. D. Hickey, L. A. Weber, and C. Baglioni, Proc. Nut. Acad. Sci. U.S.A., 1976,73, 19. l7O G. Chaconas, J. H. van de Sande, and R. B. Church, Analyt. Biochem., 1975, 69, 312. lo2 183

175

Nucleotides and Nucleic Acids

this case poly[d(A-T)]} and DNA-directed RNA p01ymerase.l~~~ 172 The ratios of 3H and 14Cincorporated into polymer give the relative specific activities, and isotopedilution techniques afford the absolute values. This method is usefully applicable to determination of sizes of pools of ribonucleoside triphosphate, and a similar method employing DNA polymerase has been described for the determination of picomole amounts of dCMP.173 The quantitative separation of nucleotides on mercurated Sephadex columns has been described.174Oligo(dT)-cellulose forms a complex with the poly(rA) tail of mouse globin mRNA. If deoxyribonucleosidetriphosphates and reverse transcriptase are added to this system, copy synthesis takes place to add the DNA complementary to mouse globin mRNA to the oligo(dT) tract. After washing with dilute alkali to hydrolyse the ribonucleic acid, the resulting complementary DNA column may be used to quantitate globin mRNA, a powerful new analytical method.175DNA columns have been prepared by adding DNA in DMSO to diazotized 3-aminobenzyloxymethylcellulose.1713 The determination of the molecular weight of animal cell RNA, using electrophoresis on exponential polyacrylamide gels under fully denaturing conditions, has been described. Effects due to RNA secondary structure are fully suppressed if dry formamide and high temperatures are used.17 In an elegant method for the isolatim of translating ribosomes, the dihydrazide of dithioglycollicacid is first attached to cellulose, and treated with poly(rU) which has been oxidized at the 3’-terminus with periodate, to form (83). After passage of a 0

II

0-P-0-

Cellulose -CONHNHCOC&-

S-S

[ Poly (rU)]

““2-( A

-C€4CONH-N

H0

HO

Ura

(83)

ribosomal preparation over the column, template-bound non-translating ribosomes are removed by washing with poly(rU), and treatment with dithiothreitol then cleaves the disulphide bond of (83) to release translating ribosomes complete with tem~ 1 a t e . lPoly(rU)-Sephadex ~~ has been used to isolate duplex DNA containing (dA. dT) clusters by selective complexation to form the (dA. dT. rU) triple helix.179 Methods for isolating poly(rA)-containing RNA by precipitation with calcium R. E. Maxson, jun. and R. S. Wu, European J. Biochrm., 1976, 62, 551. A. T. Jamieson and D. R. Webb, Analyt. Biochem., 1976, 72, 212. 173 K. Brynolf, Analyt. Biochem., 1976, 72,238. 17* D. W. Gruenwedel, M. G. Heskett, and J. E. Lammert, Biochim. Biophys. Acta, 1975,402, 7. 175 S. Levy and H. Aviv, Biochemistry, 1976, 15, 1844. 176 B. E. Noyes and G. R. Stark, CelI, 1975, 5, 301. 177 G. Spohr, M.-E. Mirault, T. Imaizumi, and K. Scherrer, European J. Biochem., 1976, 62, 313. l78 N. V. Belitsina, S. M. Elizarov, M. A. Glukhova, A. S. Spirin, A. S. Butorin, and S. K. Vasilenko, F.E.B.S. Letters, 1975, 57, 262. l;‘J R. A. Flavell and F. M. van den Berg, F.E.B.S.Letters, 1975, 58, 90. 171 172

176

Organophosphorus Chemistry

ionslso or by complexation with poly(rU) adsorbed on synthetic mica181 have been described, as also have RNA separation methods employing arginine- lS2 and lysineSe~har0se.l~~ Structure Probes.-On examination of intact muscle, using 31Pn.m.r. spectroscopy, the resonances due to ATP and other phosphorylated metabolites can be identified, and quantitation of these by n.m.r. gives good agreement with chemical analysis. The coupling constants and chemical shifts for ATP suggest that it is present as the magnesium complex.184Using data drawn from the published X-ray structures of nucleoside 2’,3’- and 3’,5’-cyclic phosphates, the variation of 31Pchemical shift with ring size in cyclic phosphodiesters has been interpreted as a function of 0-P-0 bond angle and torsional angles.lSsThe variation with pH of the 31Pchemical shifts in 2’-, 3’-, and 5’-CMP and 3’-UMP, both free in solution and bound to pancreatic ribonuclease, has been studied to gain information about the nature of phosphate binding at the active site.186The influence of lanthanide ions on the shifts of the slP resonances in ATP has been studied with a view to determining its conformation in aqueous In similar studies, the binding of dTTP to DNA polymerase I and the perturbation of the phosphorus relaxation times on adding the paramagnetic manganese ion have been investigated in an attempt to determine the nature of the metal-nucleotide interaction on the enzyme.lS8

lSo

181

lE2 lS3 184 185 186 lS7

lS8

G . M. Landes and P. A. Kitos, Biochem. Biophys. Res. Comm., 1975, 66, 1209. P. Pulkrabek, K. Klier, and D. Grunberger, Analyt. Biochem., 1975, 68, 26. F. T. Jay, C. Coultas, and D. S. Jones, Nucleic Acid Res., 1976, 3, 177. D. S. Jones, H. K. Lundgren, and F. T. Jay, Nucleic Acid Res., 1976, 3, 1569. C. T. Burt, T. Glonek, and M. Biriny, J. Biol. Chem., 1976, 251, 2584. D. G. Gorenstein and D. Kar, Biochem. Biophys. RES. Comm., 1975, 65, 1073. D. G. Gorenstein, A. M. Wyrwicz, and J. Bode, J. Amer. Chem. SOC.,1976, 98, 2308. P. Tanswell, J. M. Thornton, A. V. Korda, and R. J. P. Williams, European J. Biochem., 1975, 57, 135. D. L. Sloan, L. A. Loeb, A. S. Mildvan, and R. J. Feldmann, J . Bid. Chern., 1975, 250, 8913.

9 Ylides and Related Compounds BY

D. J. H. SMITH

1 Methylenephosphoranes Preparation.-It has been shown that the stability of the ylide solution formed from the reaction of dihalogenodifluoromethanes with tertiary phosphines is due to a dynamic equilibrium which lies on the side of phosphine and phosphonium salt (Scheme 1). Ylide solutions generated from chlorodifluoroacetateare unstable since no such equilibrium is possib1e.l

+ Br2CF2 +Ph3kFzBr BrBr- Ph3kF2Br + Ph3P +Ph3P=CFz + Ph3PBrz Ph3P + C F ~ C I C O Z - + P ~ ~ P = C F ~+ C02 + C1Ph3P

Scheme 1

An improved synthesis of dichloromethylenetriphenylphosphorane has been reported.2 It can be isolated from the reaction of (dichloromethy1)triphenylphosphonium chloride with an excess of bis(triphenylphosphorany1idene)methane provided a solvent is used which is unable to donate a proton to the strongly basic ~lide.~ C1- Ph3kHC12

+

C( =PPh&

CaH&l-C6H&e

Ph3P= CCl2

+

[Ph3P-CHxPPh3]+

C1-

A number of preparations of cumulated ylides from methylenetriphenylphosphorane have been described. Reaction with geminal dihal~genoalkenes,~ thiophosgene,6and dichloro-imines (C12C=NR) gave (l), (2), and (3) respectively. Ph3P= C = C =CR2 (1)

Ph3P= C =C= S (2)

Ph3P=C=C=NR (3)

Ketenylidenetriphenylphosphorane and its thio-analogue (2) can be obtained from the corresponding ester ylides by treatment with sodium bis(trimethylsily1)amide (4).' Salt-free solutions of alkylidenetriphenylphosphoranescan be conveni1 2

3 4 5 6

7

D. G. Naae, H. S. Kesling, and D. J. Burton, Tetrahedron Letters, 1975, 3789. B. A. Clement and R. L. Soulen, J. Org. Chem., 1976,41, 556. R. Appel, F. Knoll, and H. Vettman, Angew. Chem. Internat. Edn., 1976, 15, 315. H. J. Bestman and G. Schmid, Tetrahedron Letters, 1975, 4025. Hoechst A.-G., Ger. Offen., 2409357 (Chem. Abs., 1976, 84, 31 240). H. J. Bestman and G. Schmid, Ger. Offen., 2409356 (Chem. Abs., 1976, 84, 31239). H. J. Bestman and D. Sandmeier, Angew. Chem. Internat. Edn., 1975, 14, 634.

177

178

Organophosphorus Chemistry

ently prepared using this base. * Such solutions give predominantly cis-alkenes in Wittig reactions, undergo alkylation with thiolesters, and are useful in cyclization reactions.

+

Ph3P=CHCXMe

II

NaN(SiMe3)a --+ Ph3P=C=C=X

+

NaXMe

+

HN(SiMe3)z

(4)

X

X = OorS Ph3kHzR

+

(4)

-+

HN(SiMe&

+

Ph3P=CHR

The phosphoranylidene ylide (5) has been obtained as shown in Scheme 2. When fluoride ion is exchanged by chloride ion and the compound heated to its melting point with sodium hydride, hydrogen is evolved and the bis-ylide (6) is distilled from the reaction mixture. Me3P=CHSiMes

+

MePF2 +[MeaP=CHbMe3]+ F-

+

Me3SiF

(5)

Me3P=CH2

+

Me3PF2 +( 5 )

+

M e d F-

NaH

(5)

+ CHzClz +[Me3P=CHPMe3]+ CI- +Me3P=C=PMe3 + Hz + NaCl Scheme 2

(6)

The addition of trimethyltinlithium to triphenylvinylphosphonium bromide (Scheme 3) produced a new type of metallo-ylide (7), which on addition to cyclohexanone gave (8), containing a very nucleophilic double bond, which in the +

Ph,PCH==CH,

+ Me,SnLi

-93

"'+ [Ph,P=CHCH,SnMe,

Br-

0

-CH=CH,

Reagents: i,

J

(7 )

&

CHCH, SnMe,

0 (8)

; ii, IICI

Scheme 3

example quoted was treated with hydrogen ch1oride.l O Ylides (9) containing a P-P bond are formed from the reaction of 0-silylenols of malonic esters and diethylphosphinous chloride.ll The preparation of a number of new (alkanoylmethy1ene)triphenylphosphoranes (10) from acyl imidazides has been described.la When

* 9

10

11 12

H. J. Bestman, W. Stransky, and 0. Vostrowsky, Cltem. Ber., 1976, 109, 1694. 0. Gasser and H. Schmidbaur, J . Amer. Chem. SOC., 1975,97,6282. S. J. Hannon and T. G. Traylor, J.C.S. Chem. Comm., 1975, 630. 0. I. Kolodyazhnyi, J. Gen. Chem. (U.S.S.R.), 1975, 45, 2518. M. Miyano and M. A. Stealey, J. Org. Chem., 1975,40, 2840.

Ylides and Related Compounds Me,SiO,

Et,PCI

179 + Et,P=

lto/C=CHco~R-

RCH2COC1

H

I

C(CO,R),

Et,YCH(CO,R), 3. CH,(CO,R),

Ph,P=CH,

RCH,CO

___f

f

~

RCH,COCH=PPh, (10)

Ph,P

+

R'RS=C(CN),

Ph,P=C(CN),

-t R'SR'

(11)

mixtures of triphenylphosphine and sulphonium dicyanomethylides (1 1) are melted, trans-ylidation 0 c ~ u r s . l ~ Structure.-N.m.r. evidence has been presented which shows that the compounds generated by the reaction of butyl-lithium with methylphosphonium salts are not methylenephosphoranes, but lithiumadducts of the ylides,14and that they are planar lS (see Chapter 12). A carbonyl group separated by a benzene ring as in (12) has a weak stabilizing ef€ect.l6 Ph3€'=IICe-

COPh

Reactions.-AIdeltydes. The stereochemistry of the alkene produced from ylides generated by using 18-crown-6 complexes of potassium carbonate or butoxide, depends upon the solvent used. In THF typical 'salt free' distributions are obtained whereas in dichloromethane reversal of product distributions is 0bserved.l' A simplified method (Scheme 4) for preparing para-substituted styrenes in high

(1 3) Reagents: i, CH20; ii, NaOH.

Scheme 4

yield has been described in which a phosphonium salt (13) is suspended in formaldehyde solution and concentrated sodium hydroxide solution added.'* All three isomeric vinylogous pyridine carbaldehydes can be obtained from the corresponding K. Wallenfils, K. Friedrich, and J. Rieser, Annulen, 1976, 656. T. A. Albright and E. E. Schweizer, J. Org. Chem., 1976, 41, 1168. H. Schmidbaur, W. Richter, W. Wolf, and F. H. Kohler, Chem. Ber., 1975, 108, 2649. V. N. Listan, J. Gen. Chem. (U.S.S.R.), 1975,45, 228. l7 R. M. Boden, Synthesis, 1975, 784. l 8 R. Broos and M. Anteunis, Synthetic Comm., 1976, 6, 53. lS l4 l5 16

0rganophosphorus Chemistry

180

pyridine aldehydes and the ylide (14).laAmong ylides shown to react normally with aromatic aldehydes were (15),20 (16),21and (17).21

Ph,C=PPh, (15)

Fh,P=CHCOCOCH=PPh, (1 6 )

MeCOCOCH=PPh, (17)

.1

DMF NaOEt-EtOA

The condensation of the cinnamaldehyde derivative (1 8) with ethoxycarbonylpentyltriphenylphosphorane in DMF gave a mixture of tram-trans- and trans-cisproducts.e2A general method to prepare 1-substituted-cis-9-alkenes(19), using a stereoselective Wittig reaction, has been described.23 2,2-Dimethyl-3-butenal (20)

21

21

23

I. Hagedorn and W. Hohler, Angew. Chem. Internat. Edn., 1975, 14, 486. R. S. Tewari, N. Kumari, and P. S. Kendurkar, 2. Naturforsch., 1975, 30b, 513 (Chem. Abs., 1975, 83, 163764). M. I. Shevchuk, V. N. Kushnir, V. A. Dombrovskii, M. W. Khalaturnik, and A. V. Dombrovskii, J . Gen. Chem. (U.S.S.R.),1975, 45, 1208. N. Viswanathan, V. Balakrishnan, B. S. Joshi, and W. von Philipsborn, Helv. Chim. Acta, 1975, 58, 2026. H. J. Bestman, W. Stransky, 0. Vostrowsky, and P. Range, Chem. Ber., 1975, 108, 3582.

Ylides and Related Compounds

181

reacts with ethylidenetriphenylphosphoraneto yield exclusivelycis-3,3-dimethylhexa1,4-diene.a4The reaction of the epoxy-aldehyde (21) with stabilized ylides proceeds unexceptionally to give trans-alkenes.2sCondensation of the lactams (22) with ylides Ph ,P=C H R2

AJ(OH O R'

+

o-(--q NH R'

NH

l H

R'

affords high yields of alkenylamides (Scheme 5).26 Low-temperature 31Pn.m.r. studies27 indicate that the reaction of ylides with benzaldehyde or formaldehyde under salt-free conditions gives oxaphosphetans (23). In the presence of lithium salts, especially in ether, (24) is formed. The reaction of ylides with substituted benzaldehyde has a Hammett p of 1.1, which the authors suggest shows that the reaction proceeds via a highly polar transition state with the ylide acting as a nucleophile.

Ph,P=CR'R2

+ R3CH0 --+

Ph,P

J$i ' 0

(23)

R'

Ph,kR1R'CHR30Li

= R2 = HorMe

R3 = H o r Ph

(24)

The phosphazinium bromides (25), conveniently prepared from hydrazinotriphenylphosphonium bromide and orthoesters, when treated with base (Scheme 6) give the thermally stable ylides as a mixture of syn- and anti-forms.28These ylides are converted efficiently by various aromatic aldehydes into mixed azines. OMe

Ph,hN H-N=

C/'Me

.R'

i,ii

~

ArCH=N-N=C'

R'

Reagents: i, base; ii, ArCHO.

Scheme 6

Ketones. Treatment of the diketone (26) with methylenetriphenylphosphorane gave a high yield of 1,6-dimethylene~yclodecane.~~ Diphenylcyclobutenedione reacts with ylides, e.g. (27), to yield substituted 4-methylene derivative^.^^ 24 25 26 27

28 29

30

R. G. Salomon and N. E. Sanadi, J. Amer. Chem. SOC.,1975,97,6214. S. Masamune, C. U. Kim, K. E. Wilson, G. 0.Spessard, P. E. Georghiou, and G. S . Bates, J. Amer. Chem. SOC.,1975, 97, 3512. J. J. J. de Boer and W. N. Speckamp, Tetrahedron Letters, 1975, 4039. M. Schlosser, A. Piskala, C. Tarchini, and H. B. Tuong, Chimia (Switz.), 1975, 29,341 (Chem. Abs., 1975, 83, 177729). G. B. Merrill and H. Shechter, Tetrahedron Letters, 1975, 4527. A. K. Koli, J, Indian Chem. Sac., 1974, 51, 1012 (Chem. A h . , 1975, 83, 130678). W. Ried, H. Knorr, and U. Knorr, Chem. Ber., 1976, 109,1506.

7

Organophosphorus Cheniistry

182

The reaction of steviol norketone (28) with [3H]methyltriphenylphosphonium bromide in the presence of potassium t-butoxide (Scheme 7) has been used in the

+

i l

Reagent: i, KOBut-THF.

Scheme 7

preparation of labelled gibberellin derivative^.^' Scrambling of the label occurred between the ylide and (28). The reaction gave equal amounts of the required E3H]steviol and its stereoisomer (29). Epimerization also occurs during the treatment of (30) with methylenetriphenylph~sphorane.~?

31

32

J. R. Bearder, V. M. Frydman, P. Gaskin, J. MacMillan, C. M. Wels, and B. D. Phinney, J.C.S. Perkin I , 1976, 173. M. Deighton, C. R. Hughes, and R. Ramage, J.C.S. Chem. Comm., 1975, 662.

183

Ylides and Related Compounds

P~,~H,RI NaOR2 '

mJ

YhO

(31)

3P-Phenoxy derivatives (31) are formed in substantial amounts, particularly after long reaction times, in the Wittig reaction of pregnenolone using triphenylphosphonium Other Carbonyl Compounds. The reaction of alkylidenetriphenylphosphoranes with lactones (Scheme 8) affords betaines (32), which can be thermally decomposed to eliminate triphenylphosphine, giving lactones in which the alkylidene grouping of the starting ylide is incorporated into the ring.34

c-:>

Ph,kHR'[CH2InCOg -%

/I 0

(32) 0

Reagents: i, Ph3P=CHR1; ii, heat.

Scheme 8

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).36Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).3sQuinoline derivatives, e.g. (35), are obtained from the condensation of dicarboalkoxy-ylides with i~ocyanates.~~ Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide 33 34 35

36

37 38 39

J. P. Schmid, M. Piraux, and J. F. Pilette, J. Org. Chem., 1975, 40, 1586. K. Kise, Y. Arase, S. Shiraishi, M. Seno, and T. Asahara, J.C.S. Chem. Comm., 1976, 299. V. Subramanyam, E. H. Silver, and A. H. Soloway, J. Org. Chenz., 1976, 41, 1272. W. Flitsch, J. Schwiezer, and U. Strunk, Annalen, 1975, 1967. H. Wittmann and D. Sobhi, 2. Naturforsch., 1975, 30b, 766 (Chem. Abs., 1976, 84, 4834). A. F. Tolochko, I. U. Megera, L. V. Zykova, and M. I. Shevchuk, J . Gen. Chem. (U.S.S.R.), 1975,45,2116. W. Lwowski and B. J. Walker, J.C.S. Perkin I , 1975, 1309.

Organophosphorus Chemistry

184 Ph,P=CHCO,Et

f

HC0,Et --+ EtOCH=CHC02Et

(3 3) CH,CO,Et S

Ph,P=CHCOAr

f

+ F%,P=CHCO,Et

SCNCOPh

_+

+

Ph,P=CCOAr

ArCOCOCSNHCQPh

HzSeo3

I S=CNHCOPh (36)

Ph,P=yCONHNMe, Ph,P=CHR

+

7

Me$-N

*&x, But

I

C0,Et

Ph,P=CCONHBut

1

(37)

COPh Scheme 9

Organometallics. Methylenetriphenylphosphoranes form stable 2 :1 complexes (38)"O and 1 : 1 complexes (39)*l when treated with copper(1) o r silver(1) chlorides. Stable adducts (40) can also be obtained from the reaction of methylenetrimethylphosphorane and metal t r i a l k y l ~ . ~ ~ Ph,PCHMCHPPh,

I t R R

Ph,PCH-MCl

[

i,,

(38)

(39)

I.

M = CuorAg Me,P=CH,

+

MR, --+ M&&MR, (40)

M = Ga,In,orTl R = Meor Et 40 41 42

Y . Yamamoto and H. Schmidbaur, J. Organometallic Chem., 1975, 96, 133. Y. Yamamoto and H. Schmidbaur, J. Organornetallic Chem., 1975, 97, 479. H. Schmidbaur, H. J. Fuller, and F. H. Kohler, J. Organometallic Chem., 1975, 99, 353.

185

Ylides and Related Compounds R,P=CHz

+

__t_

[

]

?5

Me,Si-SiMe,

Me

---+ R,P=CHSiCH$iMe, Me (41)

Me, Si=)Sih4e2

R = MeorEt Me,MCH=C=O

+ Ph,P=CHCO,Me

-+ Me,MCH=C=CHCO,Me

(43)

Silylated ylides (41) are produced from alkylidenetrialkylphosphoranes and 1,3disilacyclobutanes.43These reactions are thought to proceed via penta-alkylphosphorane intermediates since cleavage of 1,l-dimethylsilacyclobutanegave only (42). Penta-alkylphosphorane intermediates are also inferred from the products of the reaction of these ylides with silacyclobutane, from which hydrogen is eliminated.44 However, the cyclobutanering is left intact when the reaction is carried out with more bulky ylides (Scheme Silicon- and germanium-substituted allenes have been prepared by the reaction of monometallated ketens with stable ylides, e.g. (43).46 R,P=CH,

+ H,Si

3

"=Y (Me,CH),P=C'

'si3 H'

MeSi

H Scheme 10 43

44 45 46

H. Schmidbaur and W. Wolf, Chem. Ber., 1975,108,2834. H. Schmidbaur and W. Wolf, Chem. Ber., 1975,108,2842. H. Schmidbaur and W. Wolf, Chem. Ber., 1975,108,2851. V. Y.Orlos, S. A. Lebedev, S. V. Ponomarev, and I. F. Lutsenko, J . Gen. Chem. (U.S.S.R.), 1975, 45, 696.

186

Organophosphorus Chemistry

Miscellaneous. An interesting synthesis of 1,l-difluoro-1-alkenes from ylides and chlorodifluoromethane has been described?' The ylide acts both as a carbene generator and trapping agent (Scheme 11). Ph,P=CR1R2

+ HCF,Cl

ph,P=CR'Rz

+

Ph3kHR1RZ+ [:CF,]

-+

Ph,P

[:CF,]

+ F2C=CR1R2 88-100%

Scheme 11

A rather complex mixture of products is obtained from the reaction of benzylidenetriphenylphosphorane and CS2.48The major product from the reaction of diphenyl disulphide with methylenetriphenylphosphorane is tris(pheny1thio)methane (44) and only a trace of the insertion product bis(pheny1thio)methane is isolated.4vPresumably the salt (45) is deprotonated before it can react with the phenylthioate anion (Scheme 12). a-Thiocarbonyl-stabilizedylides (46) are obtained O from the reaction of ylides with S-alkyl thiolcarboxylate~.~ Ph,P=CH,

PhS- + PhSCH2$Ph,

* (PhS),CH,

(45)

(PhS),CH

t--

PhS-

+ (PhS),CH$Ph,

(44) Reagents: i, (PhS)z; ii, Ph3P=CHz.

PhSCH=PPh,

Scheme 12

Alkylidenetriphenylphosphoranes are oxidized by phosphite-ozone ad duct^.^^ Ylides of the general structure (47) afford alkenes (R1or R2 = H) or ketones (R1or R2 # H). N.m.r. evidence suggests that the former reaction proceeds via a quinquecovalent phosphorus intermediate (Scheme 13). The mechanism of hydrolysis of benzylidenetriphenylphosphorane is similar to It is proposed that the low polarities that of the corresponding phosphonium of the solutions in which ylides are usually hydrolysed increase the equilibrium 4' 48 49

50

5l 52

G . A. Wheaton and D. J. Burton, Tetrahedron Letters, 1976, 895. G. Purrello and P. Fiadaca, J.C.S. Perkin I , 1976, 692. L. Field and C. H. Banks, J. Org. Chem., 1975, 40,2774. H. Yoshida, H. Matsuura, T. Ogata, and S. Inokawa, Bull. Chem. SOC.Japan, 1975,48,2907. H. J. Bestman, L. Kisielowski, and W. Distler, Angew. Chem. Znternat. Edn., 1976, 15, 298. A. Schnell, J. G. Dawber, and J. C. Tebby, J.C.S. Perkin If, 1976, 633.

187

Ylides and Related Compounds

R’

/

R’,R2 # 11

R’ ‘C=PPh,

R”

+

A.

+ (PhO),P=O

‘C=O

+ %,Po

R2/

‘2

(Ph0)P

(47)

(PhO),P=O

+ Ph,PO + R2CH0

J

R*HC=PPh,

H R2 ‘\

+-

R2CH=CHR2

P P h ,

R2 Scheme 13

concentration of the hydroxyphosphorane at the expense of the phosphonium hydroxide (Scheme 14). Rate increases of more than lo6 were obtained by reduction of the water content in the medium. P h , k H , Ph Br- \t,

Ph,kH,Ph OHPh,P=CHPh

f

H,O

&

T/i

% Ph,PCH,Ph A

Ph,PO

P

OH I

-ICIi,Ph

Reagents: i, NaOH; ii, OH-.

Scheme 14

2 Phosphoranes of Special Interest The ylide anion (48) reacts with a variety of electrophiles at the terminal carbanion site to form p-keto-ylides, e.g. (49). 63,64 The reaction between the ylide derived from cyclobutyltriphenylphosphonium bromide and cyclobutanone gave a reasonable yield of bicyclobutylidene (50).66 53 54

55

E. A. Sancaktar, J. D. Taylor, J. V. Hay, and J. F. Wolfe, J . Org. Chem., 1976,41, 509. M. Schwarz, J. E. Oliver, and P. E. Sonnet, J. Org. Chem., 1975,40, 2410. L. K. Bee, J. Beeby, J. W. Everett, and P. J. Garratt, J. Org. Chern., 1975, 40, 2212.

188 Ph;P=CHCOCH3

Organophosphorus Chemistry BuLi

*

PIi,P===CHCOCH2-

C'13CH0 t

PII,P=CIICOCH,CI-IOHCI-I, (49)

(48)

(SO) 31% An acid- and base-sensitivesiloxycarboxylicacid was treated with NN'-carbonyldiimidazole and the resulting imidazolide (51) transformed into the desired ylide using one equivalent of salt-free methylenetriphenylphosphorane in benzene, rather than two equivalents as usually recommended. Coupling, under neutral conditions, with two equivalents of aldehyde (52) gave a mixture of diastereomeric epoxythiolates (Scheme 15).66 0

II

ph3P=CHCY

0

Scheme 15

a-Oxo-y-enaminomethylenephosphoranes (53) can be obtained from readily available isoxazole derivative^.^' These ylides show a reactivity comparable to that of those stabilized by a single carbonyl group, reacting with aromatic aldehydes to give compounds (54) which can be hydrolysed by aqueous HCl to the tricarbonyl-substituted alkenes (Scheme 16). Michael additions occur between (diethoxyviny1idene)triphenylphosphoraneand carbonyl compounds which have an a-CHz. The initial products eliminate EtOH to 56

S. Masamune, H. Yamamoto, S. Kamata, and A. Fukazawa, J . Amer. Chem. Soc., 1975, 97,

57

P. Bravo and C. Ticozzi, Chem. and Ind., 1975, 1018.

3513.

189

Ylides and Related Compounds

RT=O

R,C+O R'H *H=cHAr ,N

il I II

0

RCCHCCH=CHAr

0 0 Reagents: i,

H2,Raney

(54) Ni; ii, BuLi-THF; iii, ArCHO; iv, dil. HCI.

Scheme 16

give the ylides ( 5 3 , which with aldehydes give en01 ethers (Scheme 17).68When the a-positions are blocked, allenes may be formed, e.g. (56).6s OEt

Ph,P=C=C(OEt),

f

R'CH,CR2

ll

r

I I II OEt 0

Ph,P=CHCCH@CR*

0

J-E~OH

YEt R3CH=CHd=CR1COR2

<

R3cH0

Ph,P=CHC=CR1CR2

I

OEt

I

0

(55)

Scheme 17

The (aziridin-1-y1imino)phosphoranes (57) react with ketens to give nitrile derivatives, presumably from an intermediate ketenimine by breaking the N-N bond and migration of the aziridinyl group.6oThey also react with acyl halides and 5* 59 60

H. J. Bestman and R. W. Saalfrank, Chern. Ber., 1976, 109, 403. R. W. Saalfrank, Tetrahedron Letters, 1975, 4405. J. Schweng and E. Zbiral, Tetrahedron, 1975, 31, 1823.

0rganophosph o w Chemistvy

190

Ph3P=N(57)

PhCOX I

j.

Scheme 18

isocyanates61 as shown in Scheme 18. The reaction of the phosphorane (58) with aldehydes depends upon the reaction conditions, particularly upon the presence of a base (Scheme 19).62 0

II

Ph,P=CHCOCH:P(OE

<

II

(EtO),PCH,COCH=CHR

0 t),

(58) Reagents: i, RCHO; ii, C6He; iii, NaH-DME.

Ph,P==CHCOCH--CHR

Scheme 19

3 Selected Applications of Ylides in Synthesis Heterocycles.-The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /3-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphosphonium salt (61) and sodium carboxylates (Scheme 21).s4Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y-H bond and a carbonyl or nitroso-function, as shown in Scheme 61 62

63 64

65

E. Keschmann and E. Zbiral, Tetrahedron, 1975, 31, 1817. A. Hercouet and M. Le Corre, Tetrahedron Letters, 1976, 825. J. P. Marino and R. C. Landick, Tetrahedron Letters, 1975, 4531. W. G. Dauben and D. J. Hart, Tetrahedron Letters, 1975, 4353. H. J. Bestman, G. Schmid, and D. Sandmeier, Angew. Chem. Internat. Edn., 1976, 15, 115.

191

Reagent: i, HCI.

Scheme 20

(61)

Reagents: i, RC02Na; ii, HMPT.

Scheme 21

Ph,P= C =C =0

Ph,P=C=C=X

+

Ph,P=

CH

\

_j_

c=x -+ I Z\A/y

o=zvyH o=z\A/y Scheme 22

The addition of stabilized ylides, e.g. (63), to nitrile imides or oxides gave pyrazoles or isoxazoles respectively (Scheme 23), in extremely clean reactions which probably proceed by electrophilic attack of the dipole at the y-carbon of the phosphorane.66 P. Dalla Croce and D. Pocar, J.C.S. Perkin I, 1976, 619.

192

Organophosphorus Chemistry

NC-EH

NC-CH

II CH I

*

+

Ph,P-CH

Ph,P=CH

&-Ar

I CH +

N,

II

II

-0

(63)

Ar

NC-CH-CAr 0 ’ Reagents: i, EtsNHCl; ii, Et3N 60 “C.

Scheme 23

Nitrene intermediates are implicated in the formation of the pyrrole (64) from an azirinyl aldehyde and (65).s7 Treatment of the nitrosouracil (66) with benzylideneylides affords the corresponding theophylline derivatives.6sHydrazonic halides and keto-ylides initially give betaines (67), which ring-close to (68) on heating.sg

[7 Ph

f

PhC-PPh,

I C0,Me

-

Ph

N

CH=C /ph

-

G

1

P

h

‘C0,Me

1-

C0,Me P h o p h

C0,Me

(65)

67

68

69

A. Padwa, J. Smolanoff, and A. Tremper, J. Org. Chem., 1976, 41, 543. K. Senga, H. Kanazawa, and S. Nishigaki, J.C.S. Chem. Comm., 1976, 155. P. Dalla Croce, Ann. Chim. (Italy), 1973, 63, 867 (Chem. Abs., 1976, 84, 58138).

I3

(64)

193

YIides and Related Compounds

Pheromones.-A careful examination of the factors which affect the ratio of the cis-cis- and trans-cis-alkenesformed from thereaction of thealdehyde (69) with a nonstabilized ylide has been described.70Methods were specifically developed to give the

pheromone gossyphure, which is a 1:1 mixture. (2-0xobutylidene)triphenylphosphorane was alkylated with the bromide (70) to give a ketophosphorane, which, on basic hydrolysis (Scheme 24), gave a cockroach sex pheromone (71).64Other pheromones whose syntheses involved Wttig reactions in key steps include (72)71and (73). 73 The phosphonium salt (74)and 5-cyclohexylidene-2-pentanone are reported 73 to undergo a condensation reaction upon addition of sodium hydride. The optically

Me

I C,,H,CH(CHJ,Br

0

I1 + EtCCH=PPh3

Me

Me

I I C,,H,,CH(CH,)&H$CH=PPh, II 0

Me

Me

I

I

C,,HJ,CH(CH,),CHCCH,

II

0

(71) Reagents: i, BuLi; ii, OH-.

Scheme 24

'0

71

R. J. Anderson and C. A. Henrick, J , Amer. Chem. SOC.,1975, 97,4327. H. J. Bestman, K. H. Koschatzky, W. Stransky, and 0. Vostrowsky, Tetrahedron Letters, 1976, 353.

72

73

A. W. Burgstahler, L. 0. Weigel, W. J. Bell, and M. K. Rust, J. Org. Chem., 1975, 40, 3456. J. A. Findlay, U.S.P. 3845088 (Chern. Abs., 1975, 83, 193557).

1 94

--

Organophosphorirs Cheniistry CH(CH,),CBMe 9

Ph,P(CH,),COMe (74)

pure isomers of sulcatol, a population aggregation pheromone, can be obtained from the pure lactols (75) and isopropylidenetriphenylphosphorane.'* Prostaglandins.-Ylides continue to find wide application in the synthesis of prostaglandins, either in reactions with lactols of the general structure (76) or with substituted cyclopentyl aldehydes of the type (77). Among those ylides used with lactols were (78),76(79),76977(80),78 (81),79 and (82)80and among those added to aldehydes was (83).81The six-membered lactol(84) reacts very slowly with the Wittig reagent (79).82The reaction of (85) with the sodium salt of (79) gave (86) as the main

74

75 76

77 78 79

81 g2

83

K. Mori, Tetrahedron, 1975, 31, 3011. M. Hayashi and H. Miyake, Japan Kokai, 74 116068 (Chem. Abs., 1975, 82, 170200). P. A. Grieco, C . S. Pogonowski, and M. Miyashita, J.C.S. Chem. Comm., 1975, 592. M. Hayashi, S. Kori, and H. Miyake, Japan Kokai, 75 49259 (Chem. Abs., 1975,83, 20582). P. Bollinger, Ger. Offen., 2431 930 (Chem. Abs., 1975, 83, 58248). H. J. E. Hess, L. J. Czuba, and T. K. Schaaf, U.S.P. 3928391 (Chem. Abs., 1976, 84,121 292). M. Hayashi, S. Koori, and Y . Iguchi, Japan Kokai, 75 35 133 (Chem. Abs., 1976, 84,43430). M. Hayashi, S. Koori, H. Wakatsuka, M. Kawnmura, and Y . Konishi, Japan Kokai, 75 137961 (Chem. A h . , 1976, 84, 164253). N. Nakamura and K. Sakai, Tetrahedron Letters, 1976, 2049. K. Kojima and K. Sakai, Tetrahedron Letters, 1976, 101.

195

Ylides and Related Compounds

Ph3P= C€I(CH,)3S0,H

Ph3P= CHCHO

Carbohydrates.-The acid (87), an intermediate in the synthesis of oxaprostaglandin derivatives from D-ribofuranose sugars,84is obtained from the aldehyde (88) and the sodium salt of (79). The condensation of 2,5-anhydro-~-allosederivatives with (89) gave the expected products (90).86Similarly, 1,Cfuranoses (91) afford (92).86These unsaturated halides are useful intermediates for further modifications.

6HO

Reaction of the ketones (93) with excess methylenetriphenylphosphorane gave, not only the expected methylene compounds, but also the diene (94) formed by elimina84 85 86

G. J. Lourens and J. M. Koekemoer, Tetrahedron Letters, 1975, 3715. D. B. Repke, H. P. Aibrecht, and J. G. Moffatt, J. Org. Chem., 1975, 40, 248. J. M. J. Tronchet, 0. Martin, J. B. Zumwald, N. Le-Hong, and F. Perret, Helv. Chim. Acta, 1975,58, 1735.

Organophosphorus Chemistry

196

RoH2vHo

,COMe

RO

OR

/X

X\

tion of the 3-alko~y-group.~~ The addition of (chlorofluoromethy1ene)triphenylphosphorane to (95) produced (96) as a mixture of geometrical isomers.88

Carotenoids.-In studies designed to elucidate the configurations of the central triene chromophores of phytoenes, the condensation of allylic phosphonium salts with ag-unsaturated aldehydes (97) gave thenewly formed double bond as a mixture of cisand trans-forms.8gIn a similar way the condensation of (98) with the geometrical isomers of citral gave a mixture, demonstrating that the a-double bond of the salt O Also synthesized by similar reactions were dehydroflexiretains its configurati~n.~ xanthin (99) O1 and ~&carotene-2,2’-diol 87 88

8g 90

91 92

J. M. J. Tronchet, C. Cottet, and F. Barbalat-Rey, Helu. Chim. Actu, 1975, 58, 1501. J. M. J. Tronchet, D. Schwarzenbach, and F. Barbalat-Rey, Carbohydrate Res., 1976, 46, 9 (Chem. Abs., 1976, 84,90440). N. Khan, D. E. Loeber, T. P. Toube, and B. C. L. Weedon, J.C.S. Perkin Z, 1975, 1457. L. Barlow and G. Pattenden, J.C.S. Perkin I , 1976, 1029. R. E. Coman and B. C. L. Weedon, J.C.S. Perkin I , 1975, 2529. K. Tsukida, K. Saiki, M. Ito, I. Tomofuji, and M. Ogawa, J. Nutr. Sci. Vitaminol., 1975,21, 147 (Chem. A h . , 1975, 83, 131 784).

197

Ylides and Related Compounds

X-/\kh,

Br-

+R&+Jo )=/-'"( _.)

.t

(97)

R R = n-C,&,

+

x/\hl

hPh, (98)

Condensations with the dialdehyde (101) have also been used as outlined in Scheme 25. Thus carotenoids of the 1 ,Zdihydro-series (102), thought to be constituents of photosynthetic bacteria,93and those from naturally occurring irones (103) 94 have been successfully prepared.

93

A. Eidem, R. Buchecker, H. Kjosen, and S. Liaaen-Jensen, Acta Chem. Scand. (B), 1975,29,

94

A. G. Andrewes, G. Borch, and S. Liaaen-Jensen, Acta Chem. Scand. (B), 1976, 30, 214.

1015.

Reagents: i, CHz=CHMgBr; ii, PhaPHBr; iii,

1 \/\/\A/\ (101)

l

o

Scheme 25

Non-Benzenoid Aromatic Compounds.-The synthesis of aromatic molecules containing small, medium, and large rings, using the reaction of dicarbonyl compounds and bis-ylides, has been thoroughly reviewed.95

+

95

K. P. C . Vollhardt, Synthesis, 1975, 765.

Ylides and Related Compoirnds

1 99

The interesting hydrocarbon (104), having both aromatic and anti-aromatic character, could be isolated in low yield by treatment of a bis-ylide with freshly distilled g l y o ~ a lPrecursors .~~ for the preparation of helicenes, e.g. (105), have been synthesized in one-step reactions. The yield of the double Wittig reaction is better using a di-aldehyde rather than a bisphosphoniuni salt. The [12]-annulene (106) is obtained from the reaction of the bis-ylide derived from (107) and a d i - a l d e h ~ d e . ~ ~ The condensation of (107) with two moles of 3-methylpent-2-en-4-yn-l-al (108) was also successful.g g

4 Selected Applications of Phosphonate Carbanions General.-The relatively unreactive diethyl arylmethylphosphonateshave been used quite successfully in alkene synthesis with phase-transfer cata1ysis.l O O In a comparative study it was shown that anions derived from b-ketophosphonamides (109) have very low reactivity whereas those from 8-ketophosphonates (110) react quite well with aldehydes to give trans-alkenes.lo1Benzyl dimethyl phosphonoacetate (111) can be used to form alkenes, e.g. (112), from which the benzyl group can be removed by hydrogenolysis without disturbing the C=C bond.Io2The carbanions (1 13) can be

B8

C . F. Wilcox, J. P. Uetrecht, G. D. Brantham, and K. G. Grohman,J. Amer. Chem. SOC.,1975, 97, 1914.

R. H. Martin and M. Baes, Tetrahedron, 1975, 31, 2135. R. H. Wightman and F. Sondheimer, Tetrahedron Letters, 1975, 4179. 99 R. R. Jones, J. M. Brown, and F. Sondheimer, Tetrahedron Letters, 1975, 4183. l o o C. Piechucki, Synthesis, 1976, 187. Io1 W. G. Dauben, G. H. Beasley, M. D. Broadhurst, B. Muller, D. J. Peppard, P. Pesnelle, and C. Suter, J. Amer. Chem. SOC.,1975, 97, 4973. 102 J. C. Bradley and G. Buchi, J. Org. Chem., 1976, 41, 699. 97

g~

200

Organophosphorus Chemistry 0

II

+ (MeO),PCH,CO,CH,Ph

ct

(111)

C -/02Me

(1 12).

R = Ph,SPh

directly or-chlorinated using carbon tetrach10ride.l~~~ lo4 Subsequent treatment with carbonyl compounds gives 1-chloroalkenes.In a similar fashion, 1,l-dibromoalkenes can be obtained (Scheme 26).lo6 0

0

II

(EtO),PCHBr,

(EtO),PCH2Cl

II

R‘ iii’iv*

>C=CBr2 R2

Reagents: i, BuLi; ii, CBr4-LiBr; iii, LiNPi-LiBr; iv, R1R2C=0.

Scheme 26

Among those phosphonates used successfully in alkene synthesis with aromatic aldehydes were (1 14),lo6(1 15),lo7(1 16),lo8(1 17),lo9and (1 18).110The stereochemical 0

lo3 J. Petrova, P. Coutrot, M. Drew, and P. Savignac, Synthesis, 1975, 658. lo4 P. Coutrot, C. Laurenco, J. Petrova, and P. Savignac, Synthesis, 1976, 107. l o 5 P. Savignac and P. Coutrot, Synthesis, 1976, 197. lo6 C. Rivalle, J. A. Louisfert, and E. Bisagni, Tetrahedron, 1976, 32, 829. 107

A. Jurasek, J. Kovac, and J. Prousek, Chem. Zvesti, 1975, 29, 234 (Chem. Abs., 1975, 83, 96900).

lo* M.

Hattori and S. Sato, Nippon Kugaku Kuishi, 1975, 1780 (Chem. A h . , 1975, 84, 4079). and K. L. Cammack, J. Org. Chem., 1975, 40, 1731. and H. Ulrich, J. Org. Chem., 1975, 40, 2243.

log J. W. Worley, K. W. Ratts, 110 G. M. Peters, F. A. Stuber,

201

Ylides and Related Compounds

course of the reaction of 2-furylketones with the phosphonoacetate (119) has been studied in some detail.lll The 1,3,5-trisubstituted benzene derivative (120) was obtained from the tri-anion (121).l12

0

CHAr

II CHY(OEt),

II

CH

I

I

(EtO),PZ]HSMe

II 0I1

0

R'R2c=0+

MeSCH-C

II

0

/

2R'

The synthesis of orp-unsaturated sulphoxides from the anion (122) has been described.llS The reaction is non-stereospecific, but good yields are obtained from cyclopentanones and acetophenones. Good yields of mono-alkylated products are obtained from the reaction of carbanions of diethyl 2-oxophosphonates (123) and reactive halides;ll* alkylation of the compounds (124) has also been achieved.lls The

M. Gernayova, J. Kovac, M. Dandarova, B. Hasova, and R. Palovcik, Coll. Czech. Chem.

ll1

Comm., 1976,41,764. L. Ya. Malkes, L. Ya. Kheifets, and N. P. Kovalenko, Stsintill. Org. Lyuminofory, 1972, 32 (Chem. A h . , 1975, 83,96820). M. Mikolajczyk, S. Grzejszczak, and A. Zatorski, J. Org. Chem., 1975,40, 1979. 114 R. D. Clark, L. G. Kozar, and C. H. Heathcock, Synthesis, 1975, 635. 115 J. Blanchard, N. Collignon, P. Savignac, and H. Normant, Synthesis, 1975, 655.

112

202

Orgunophosphonw Chemistrjy

CHP(OR), + PhCH=NAr

--+

CH-CHPh

+

R

CHP(0Rj,

I

PhCHNHAr (125)

carbanions of 2-thienylmethylphosphonicacid esters react with Schiff bases to form a mixture of (125) and trans-l-pheny1-2-(2-thienyl)ethylene(126).l16A further report on the reaction of the pyrroline N-oxide (127) with the phosphonates (128) shows that the products obtained depend upon the conditions used (Scheme 27).l17 The 0

+

II

1 ,

\

H

\

Reagents: i, NaH-DME; ii, NaOEt-EtOH.

Scheme 27

condensation of phosphonate anions (129) with ketens is the best way of preparing allenecarboxylic acid esters (13O).ll8

Natural Products.-The use of 2-oxoalkylphosphonates still appears to be the method of choice for the preparation of the C ,-side-chain of prostaglandins. Examples reported this year were in the preparation of azaprostaglandin~,~~~ aryl analogues,12oand the analogue (131),la1among others. Royal jelly acid has been

l20

M. Kirilov, J. Petrova, S. Momchilova, and B. Galunski, Chern. Ber., 1976, 109, 1693. E. Breuer, S. Zbaida, J. Pesso, and S . Levi, Tetrahedron Letters, 1975, 3103. W. Runge, G. Kresze, and E. Ruch, Annalen, 1975, 1361. J. W. Bruin, H. de Koning, and H. 0. Huisman, Tetrahedron Letters, 1975, 4599. M. R. Johnson, H. J. E. Hess, T. K. Schaaf, and J. S. Bindra, Ger. Offen., 2353 159 (Chern.

121

A h . , 1975, 83, 58094). 0. G. Plantema, H. de Koning, and H. 0. Huisman, Tetrahedron Letters, 1975, 4595.

l16 117 118

119

203

Ylides aid Related Cornpowids ,OCH,SPh

N

,OCH.$Ph

N

synthesized, using the reaction of the aldehyde (132) with (119) followed by hydrolysis.122Similar reactions also gave exclusively tu~rzs-alkenes.~~~~ 124 Trifluoromethylsubstituted ketones have enhanced reactivity with phosphonate anions, as shown in the synthesis of analogues (133) of juvenile hormones.126The condensation of the phosphonate (135) with the optically active aldehyde (134) is a key step in the synthesis of bacterioreberin carotenoids.126

R = hIe,C=CH(CH,),-

122 123 124 125

(133)

0.P. Vig, A. K. Vig, J. S. Mann, and K. C. Gupta, J. Indian Chem. SOC.,1975,52,538 (Chem. A h . , 1975, 83, 192487). 0. P. Vig, A. K. Vig, M. S. Grewal, and K. C. Gupta, J. Indian Chem. SOC.,1975, 52, 543 (Chem. A h . , 1975,83, 192488). 0. P. Vig, A. K. Vig, A. L. Ganba, and K . C. Gupta, J. Indian Chem. SOC.,1975, 52, 541 (Chem. A h . , 1975,83, 192473). F. Camps, J. Coll, A. Messegner, and A, Roca, Tetrahedron Letters, 1976, 791. J. E. Johansen and S. Liaaen-Jensen, Tetrahedron Letters, 1976, 955.

10 Phosp hazenes BY R. KEAT

1 Introduction Interest in the basic chemistry of these compounds continues at about the same level as last year, except that the number of publications dealing with their applications has again increased. Review articles are mainly limited to the plenary lectures of the 1974 Prague Symposium on Inorganic Phosphorus Compounds, where relevant titles are: ‘Aspects of Structure and Bonding in Inorganic Phosphorus Compounds’,l ‘New Examination of Halides and Chalcogens of Phosphorus’,2 ‘Results and Problems connected with the P-N Bond’,3 and ‘Photoelectron Spectra and Bonding in Phosphorus compound^'.^ An attempt has been made to rationalize the bond angles at nitrogen in phosphazenes in terms of steric interactions. Finally, an excellent account of the properties and applications of polyphosphazenes derived from (NPCI,), has been published. 2 Synthesis of Acyclic Phosphazenes From Amines and Phosphorus(v) Halides.-Given a suitable primary amine, the Kirsanov reaction remains one of the most convenient routes to these compounds, e.g. (1) and (2).8In both investigations the trichlorophosphazenes were characterized by their now familiar reaction with formic acid :

RNzPC13

+

HC02H+RNHP(O)Cl2

+

HCl

+

CO

Where the phosphazene is dimeric, and forms a cyclodiphosphazane, (RNPCI,),, heating in the absence of solvent results in the formation of cyclic phosphazenes (3).9 When R = acyl, the products are a nitrile and phosphoryl chloride. The results for (MeNPCI,), are in agreement with previous work.1°

1 2 3 4

5 6 7

* 9

10

R. A. Shaw, Pure Appl. Chem., 1975,44, 317. H. W. Roesky, Pure Appl. Chem., 1975, 44, 307. H.-A. Lehmann, Pure Appl. Chem., 1975,44, 221. H. Bock, Pure Appl. Chem., 1975,44, 343. C. Glidewell, J . Inorg. Nuclear Chem., 1976, 38, 669. R. E. Singler, N. S. Schneider, and G. L. Hagnauer, Polymer Eng. Sci.,1975, 15, 321. N. P. Pisanenko, I. M. Kosinskaya, and V. I. Shevchenko, J. Gen. Chem. (U.S.S.R.), 1975,45, 1678.

F. V. Bagrov and N. G. Solov’ev, J. Gen. Chem. (U.S.S.R.), 1974,44,934. C. Glidewell, Angew. Chem. Internat. Edn., 1975, 14, 826. H.-G. Horn, 2.anorg. Chem., 1974,406, 199.

204

Phosphazeiies

205

R'NH, + PC1,

-+

+ POCl, + HC1

R2N=PCl,

(2)

(R' = AlkOCOCO-,

R2 = AlkOCCJCO-)

Other examples of the Kirsanov reaction have been provided by the use of aryland alkyl-chlorophosphoranes (4),11 (5),12 (6),'3 (7),14 (8),l4 (9).16 Details of the

+

H~NCO(CF~)~CONHZPhPC14 +PhClzP=NCO(CF2)4CON=PPhC12

+

HC1

(4)

RSNH2

+ Ph3PBr2 -+RSN=PPh3 + HCl (5)

(R

= mono- and di-nitrophenyl)

H2NCaH4NH2-p

EtsN + 2RzPC13 + C ~ R ~ P = N C ~ H ~ ( N = P R ~ C+I ) -HCl E,

(6)

(R = n-C3F,) ClCHzCCl2CONHz

+ C13CPC14

RCONHz

+

ClCHzCC12CON=PC12CC13 (7) Ph2PC13 +RCON=PClPh2 HCl __+

+ C13CPC14

(R = alkyl)

HCl

+

(R = various chloroalkyl groups) RNH2

+

__+

(8)

RN=P(CCI3)C12

+

HCl

(9)

n.m.r. and i.r. spectra of the series of compounds (9) were recorded. A tendency to dimerization was noted only when R = Me. 11 12

V. P. Rudavskii, M. N. Kucherova, and N. A. Litoshenko, Khim. Tekhnol. (Kiev), 1975, 21 (Chem. Abs., 1976, 84, 31 190). T. A. Chaudri and A. R. Aziz, Pakistan J. Sci. Ind. Res., 1975, 12, 192 (Chem. Abs., 1976, 84, 74367).

14

E. I. Sokolov, V. N. Sharov, A. L. Klebanskii, V. V. Korol'ko, and V. N. Prons, J . Gen. Chem. (U.S.S.R.), 1975, 45, 2305. D. M. Zagnibeda and V. P. Rudavskii, Khim. Tekhnol. (Kieu), 1976,60 (Chem. Abs., 1976,84,

l5

E. S. Kozlov and S. N. Gaidamaka, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1904.

1.3

t64 94 1).

206

Orgarrophosphorus Chemistry

Further details of the preparation of (phosphazeny1)fluorophosphines(10) have appeared.16 The products were characterized by i.r., mass, and n.m.r. spectroscopy RPF4

+

(Me3Si)2NPF2 +RF2P=NPF2

+

Me&F

(10)

(R = ForPh)

as well as (in one case) the formation of a molybdenum carbonyl complex, (PhF2P=NPF2)2M~(C0)4. The sign and magnitude of the couplings J(16N-,lP) in the n.m.r. spectra of F,P=NPF, have also been discussed.17 The reaction of fluorophosphoranes RPF., with heptamethyldisilazane results in the formation of cyclodiphosphazanes, rather than phosphazenes:l*7l 9

+

(Me3Si)gNMe RPF4 -+ (RPF2NMe)z (R = Pri, But, or CcF5)

+

MeaSiF

The n.m.r. spectra of the alkyl compounds were studied in detail, and a crystal structure has been completed on the pentafluorophenyl-derivative.la Monomeric phosphazenes are, perhaps unexpectedly, obtained 2o from the reactions of certain lithiated imides with fluorophosphoranes:

+

RPF4 (CF&C=NLi +:RF2P =NC(CF&N(CF& + RF3PN =C(CF3)2 (R = Me, Et, F; phosphazene + LiF formed only when R = Ph).

+

LiF

The imino-nitrogen a t o m in the phosphazenes undergo an ‘isomerization’ process which is of an intermediate rate on the n.m.r. time-scale at ambient temperatures. From Azides and Phosphorus(u1) Compounds.-The reactions of aminophosphines, and of phosphites, with trimethylsilyl azide are not as simple as might be expected, in view of the formation of significant quantities of by-products, (11) and (12), which have been identified.21 (Me2N)3P + MesSiN3 + (MezN)sP=NSiMes (MezN)sP=NP(NMe2)2 =NSiMes N2 MesSiNMe2 (1 1) (Me0)3P + MesSiNs +(MeO)sP=NSiMez N2 (MeO)zP(O)NMeSiMe3 (12)

+

+

+

+

+

The influence of phosphorus basicity on the reactions of aminophosphines with azides has been nicely demonstrated by comparing the reactions of (Me,N),P, MeC(CH,NMe),P, and P(NMeNMe),P with phenyl azide.22It was argued that the base strength of the acyclic phosphine is higher because of the repulsive interactions between the nitrogen lone pairs and the phosphorus lone pair. This stabilizes the intermediate, (Me,N),P=N -N=NPh, and renders its decomposition slower than, for example, that of MeC(CH,NMe),P=N.N=NPh. The base strength of the free l6

l7

G.-V. Roschenthaler and R. Schmutzler, Z . anorg. Chem., 1975, 416, 289. J. R. Schweiger, A. H. Cowley, E. A. Cohen, P. A. Kroon, and S. L. Manatt, J. Amer. Chem.

SOC., 1974, 96, 7122. 18 19

20 21 22

R. K. Harris, M. I. M. Wazeer, 0. Schlak, and R. Schmutzler, J.C.S. Dalton, 1976, 17. M. Fild, W. S. Sheldrick, and T. Stankiewicz, Z . anorg. Chem., 1975,415,43. J. A. Gibson and R. Schmutzler, 2. anorg. Chem., 1975, 416, 222. 0. Schlak, W. Stadelmann, 0. Stelzer, and R. Schmutzler, 2. anorg. Chem., 1976, 419, 275. R . D. Kroshefsky and J. G. Verkade, Inorg. Chem., 1975, 14, 3090.

Phosphazenes

207

phosphine, MeC(CH,NMe),P, is lower because the structure imposes near orthogonality on the nitrogen and phosphorus lone pairs. Other phosphazenes generated = Ph, (PhO),PO, and Ph,PO] included (Me2N),P=NX, from azides XN, MeC(CH,NMe),P=NX, P(NMeNMe),P=NX, and XN=P(NMeNMe),P=NX. The 31Pn.m.r. spectrum of Ph,P(O)N=P(NMeNMe),P=NP(O)Ph, was re-interpreted in terms of an AA’XX’ spin system. Me,Si-SiMe, I \ MeN, p M e

-

-t

P

Me

Me2Si- SiMe, / \ MeN, ,NMe P Me’bMe,

+ N,

(13)

The phosphorus heterocycle (13) has been chara~terized,~ by a reaction with trimethylsilyl azide. Other aminophosphines have been used as precursors of phosphazenes because of interest in the physiological properties of the latter R1CsH4N3

(R2= NMe2, R1

=

+

+

R2P(NMe& +R1CsH4N=PR2(NMe2)z N2 Me, C1, NOe, CF3, or COzEt; R2 = Ph, R1 = Me)

The cyclodiphosphazanes shown in Scheme 1 were thought to have monomeric phosphazene structures, but their dimeric structure has now been established 25 by several spectroscopic methods [31Pn.m.r., s6Cln.q.r. (X = CI), i.r., mass]. Some of

0-P&

R

a

r

--+

[ R a N 3

]

-N’

X (R = H, X = Et, OMe, OEt, NEt,; R = F, X = Et; R = Br, X = ,OEt) Reagents: i, X2PCl; ii, EtsN.

Scheme 1

the compounds have also been synthesized by Kirsanov reactions on o-aminophenol. The reactions of phenolic azides with triphenylphosphine have also been investigated 26 by other workers, and in some cases a tautomerization process, e.g. between (14) and (13,was detected. Phosphazenyl sulphamoyl chloride, Ph,P=NSO,CI, may be converted into the azide either by reduction of the hydrazide Ph3P= NS02NHNH2with sodium nitrite in acid solution, or by reaction with sodium z3 H. Autzen and U. Wannagat, Z . anorg. Chem., 1976, 420, 139. 24 25

26

V. S. Petrenko, A. P. Martynyuk, L. V. Dyrenko, M. P. Kardakova, A. I. Panasyuk, and V. N. Tertyshnyi, Fiziol. Akt. Veshchestca, 1974, 6, 10 (Chem. A h . , 1975, 82, 171 140). N. A. Tikhonina, G . I. Timofeeva, E. I. Matrosov, V. A. Gilyarov, and M. I. Kabachnik, J. Gen. Chem. ( U S S R . ) , 1975, 45, 2372. H. B. Stegmann, G . Bauer, E. Breitmaisr, E. Herrmann, and K . Scheffler, Phosphorus, 1975,5,

208

Organophosphorus Chemistvy Ph

a ~ i d e .The ~ azides were converted into bis(phosphazeny1)compounds by reaction with phosphites, and less readily, thiophosphites:

+

Ph3P=NSOzNa + P(XR)3 +Ph3P=N*SOzN=P(XR)3 (X = 0, R = Alkor Ph; X = S, R = Alk)

Nz

A sulphamoyl azide has also been used in the synthesis of a phosphazenyl-stabilized ylide (16).28Aroyl azides react readily with triarylphosphines to give phosphazenes (17), 2 9 and azidoformadinium chloride may react with triphenylphosphine to give (18) .3 O MezS(0) =CHP(0Et)z

+

--+ MezS(0) =CHP(0Et)z =NSOzCsH4Me-g

p-MeC6H4SOzN3 PhP(O)(CsH*CONs-p)z

+

+ NZ

(16)

P(Cs&X-p)a

__+

(X = OMe, OEt, or Ph) (HzN)zC+N3 C1-

+

P~P(O)[C~H~CON=P(GH~X-E,)~]Z Nz (17)

+ Ph3P +[Ph3P=NN=NC(NHZ)z]+ C1-

1

heat

Ph3P=NC+(NH& C1(18)

+

Nz

Other Methods.-Only one new example of a phospha(rI1)azene has been reported :31

+

Me2N.NRLi R1RzNPC1z (R1 = Me&, R2 = But)

__+

Me2N-NR1P=NR2

+

LiCl

+

RC1

Attempts to synthesize the compound Me,N .N=PNR1R2 resulted in the formation of a cyclodiphospha(rr1)azane (19). Scheme 2 shows the products of reaction of Me,N-NR'Li

+ R1R3NPCb

RzR3NP-Nf NMe, __f

(R* = SiMe,, K2 = But, K3 = Me) 27 28

29

30 31

I

MezN. N-

I

PNR2R3

+

LiCl

+ R'CI

(19)

D, E. Arrington, J.C.S. Dalton, 1975, 1221. V. P. Lysenko, I. E. Boldeskul, R. A. Loktionova, and Yu. G. Gololobov, J . Gen. Chem. (U.S.S.R.),1975, 45, 2297. V. A. Shokol, V. V. Doroshenko, and G. I. Derkach, J. Gen. Chem. (U.S.S.R.), 1975,45, 1680. W. Buder and A. Schmidt, 2. Naturforsch., 1975, 30b, 503. 0. J. Scherer and W. Glassel, Angew. Chem. Znternat. Edn., 1975, 14, 629.

209

Phosphazenes

phosphorus trichloride with methyl hydrazone~.~~ The ionic product, for which three canonical forms are shown, is characterized by NH. -C1hydrogen bonding and by low-field 31P shifts. Chlorophosphines R2PCl and amides H2NY give P-phosphinophosphazenes in benzene solution at ambient temperatures:33 [R2HP =NY]

11

RzPCl

+ H2NY + Et3N+RzPNHY + Et3N+HC1+ R2PCl + EtSN+R2P*PR2=NY + EtsN+HCl-

RzPNHY [R = Me, Y = P(S)Me2, P(S)Ph2, P(S)(OPh)2,P(O)(OPh)2, COPh, or SOztol-p; R = Ph, Y = PPh2, P(S)Me2, P(S)Ph2, P(S)(OPh)2, SO2tol-p, or S02CF31

These, and other derivatives containing both Me and Ph R-substituents, are susceptible to hydrolysis and oxidation; for example, reaction with sulphur gave the phosphinothioyl-derivatives R2P(S)PR2=NY. The lH and 31Pn.m.r. spectra were discussed, particularly with reference to J(PP) and J(PNP), and the former coupling increases with increasing basicity of Y. The conversion of aminophosphitesinto monophosphazeneshas been a subject of particular interest. Compounds (20),34(21),36(22),56 and (23) 3 7 have been prepared. (Et0)zPNHAc

+

CH2=CXR

+(EtO)zPCH2CHXR

(R = H o r M e ; X = COZMe)

II NAc (20)

36

J. Luber and A. Schmidpeter, Angew. Chem. Infernat. Edn., 1976, 15, 111. H. Rossknecht, W. P. Lehmann, and A. Schmidpeter, Phosphorus, 1975, 5, 195. A. N. Pudovik, E. S. Batyeva, A. S. Selivanova, V. D. Nesterenko, and V. P. Finnik, J . Gen. Chem. (U.S.S.R.),1975, 45. 1659. A. N. Pudovik, 8.S. Batyeva, and E. N. Ofitserov, J. Gen. Chern. (U.S.S.R.), 1975, 45, 2057. A. N. Pudovik, 8. S. Batyeva, V. A. Al'fonsov, and Yu. N. Girfanova, J. Gen. Chem. (U.S.S.R.),

37

A. N. Pudovik, E. S. Batyeva, V. A. Al'fonsov, and Yu. N. Girfanova, J. Gen. Chem. (U.S.S.R.),

32 33

34

35

1975,45, 1606. 1975,45, 1606.

210

Organophosphorus Chemistry (Et0)zPNHSiMes

+ CH2 =CHCN --+(EtO)zPCH2CHzCN II

(Et0)zPNPhSiMes

+

NSiMe3 (21) PhCHO --+(Et0)zPCHPhOSiMes

II

NPh (22) (Et0)zPNPhX PhCHO +(Et0)2PCHPhOX II (X = MgBr or SiMe3) NPh (23)

+

It seems probable that these reactions proceed by nucleophilic attack of the phosphorus atom on the carbonyl group or activated olefin with the formation of a dipolar ion intermediate, which rearranges to a phosphazene by migration of a hydrogen atom or silyl group. Oxidation of phosphites to phosphazenes can also be achieved by reactions with diazo-compounds :

+

(RO)zPOSiMe3 N2CHC02Et _t (RO)(Me&O)P = N - N =CHCOzEt (R = Meor Et)

This phosphazene is thermally unstable and, somewhat surprisingly, the silyl group migrates to nitrogen, forming (RO),P(O)NSiMe,N=CHCO,Et at ambient temperatures. A phosphazene of related structure, also obtained from a diazo-compound, exists in tautomeric forms (24).39 N.m.r. spectroscopy shows that the proportion (Et0)zPNHPh (Et0)2P = N * N =CHCOzMe

3-

+(Et0)2PNHN= CHCOzMe

I

NzCHCOzMe

II NPh

NHPh (24)

of the second form increases with increasing solvent polarity. Trisdimethylaminophosphine and triphenylphosphine have also been used as substrates for reactions P(NMe2)3

+

MezAsCRN2 +Me2AsCR=N ’ N =P(NMe&

(R = H or COzEt; no reaction when R = MezAs)

(25)

with diazo-compounds to give (25)40 and (26).41Examples of related reactions are provided by the formation of (27).42

3* 39 40

41 4‘J

A. N. Pudovik and R. D. Gareev, J . Gen. Chem. (U.S.S.R.), 1975, 45, 220. R. D. Gareev and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.), 1974, 45, 513. P. Krommes and J. Lorbeth, J . Organometallic Cliem., 1976, 110, 195. G. Cshvrissy and D. Suciu, Annalen, 1975, 1618. K. Burger, W. Thenn, and H. Schickaneder, Cliern. Bcr., 1975, 108, 1468.

21 1

Phosphazenes jfi-6(CF3),

+ P(OR2), --+

R:C=NCMe,CH,CR:N=P(OR*),

(R' = CF,; R2 = Me, Et, or Pri)

(27)

The chloramine-T synthesis has only been applied in one study, which was directed

\

at the U.V. and i.r. spectroscopic properties of the -P=N

bond,43e.g.

/

MeC(CH20)sP

+ p-MeC6H4S02N NaCl +MeC(CH20)3P=NSOzCeHaMe-p + NaCl

in which a 16N-labelledproduct was also obtained. Comparisons of the spectra of this product with those of related acyclic phosphazenes and of (EtO),P=NC,H,X with Me, P-N MeC(CH,O),P=NC,H,X (X = NO2,N=NPh, N=NCsHaNOz, and CH: C I ) \c,NPh

II

0

indicated that the electron-donor properties of the bicyclic compounds are less than those of analogous acyclic compounds. This conclusion is in agreement with results discussed above,22and probably related by the conformational constraints imposed in the bicyclic structure. Routes to phosphazenes involving the reaction of phosphines with carbon tetrachloride in the presence of amines have been reviewed44and it has been that this type of reaction does not occur with diphosphines.It was, however,successful with a phosphonite and tosylamine (Scheme 3).46 The same product was also obtained with tosyl azide. @t0)2PCH(C02Et)~

i, ii

+ T s N H ~+(Et0)2P =C(C02Et)z I

NHTS iii

-1

(Et0)2PCH(C02Et)2

II

NTs Reagents: i, CCb; ii, Et3N; iii, heat.

Scheme 3

Further examples of the use of dichloro-amines in the synthesis of phosphazenes have appeared :, RNCh 43

-a, + ROPCl2 +[RNClP(OR)Cl2]+CI- + RN=P(OR)C12

8. S. Kozlov, A. I. Sedlov, I. N. Zhmurova, and V. G. Yurchenko, J . Gen. Chem. (U.S.S.R.),

46

1975, 45, 755. R. Appel, Angew. Chem. Internat. Edn., 1975, 14, 801. R. Appel and R. Milker, Chem. Ber., 1975, 108, 2349. L. A. Repina, R. A. Loktionova, and Yu. G. Gololobov, J. Gem Chem. (U.S.S.R.), 1975, 45,

47

A. M. Pinchuk, V. A, Kovenya, and M. I. Povolotskii,J. Gen. Chem. (U.S.S.R.), 1975,45,2352.

44

45

2298.

212

Organophosphorus Cheniistry

This reaction only occurs when the R-group is electron-withdrawing (-CMe,CN or -SO,Ph); when R = alkyl, diphosphinylamines RN[P(O)CI,], are obtained. Other synthetic routes to phosphazenes, using phosphorus(v) compounds as substrates, are more limited. An example of the reaction of a nitrile with a phosphorus(v) chloride is provided by Scheme 4.48In benzene solution, or in the absence ii

i

PhCHzCN

+ PC15 +PhCCl=CClN=PC13 +PhCC12CC12N=PC13

Reagents: i, PhCl or CC14; ii, Clz.

Scheme 4

of solvent, reaction is limited to chlorination of the methylene group to give PhCC12CN and PC13. The synthesis of phosphazenes starting from aminophosphonium salts appears to be conveniently accomplished by the reaction of the phosphonium azide with sodamide in liquid ammonia solution:4Q R3GNH2N3(R = aryl)

+ NaNH2-+NaN3 +

R3P=NH

+

NH3

It was not clear, however, how this reaction compares with other methods of deprotonation, since comparisons were only made with the route : RsP=NSiMea

KSO, __+

MeOH

R3P=NH

+

MeOSiMe3

which is most convenient when R = alkyl. Other reactions in which phosphonium salts provide starting points for phosphazene synthesis include the formation of (28)50 and (29).51The phosphazenes Ph3PNHNH2 Br-

+

++haPNHN=C(OMe)R

Br-

base

+Ph3P=N*N=C(OMe)R

RC(OMe)3

(R

=

H, Me, or Ph) Ph4$C1-

+

LiNHR+PhsP=NR (29) (R = Me, Et, Pri, Bun, but not But)

+

PhH

derived from the hydrazinophosphonium salt, which were present as a mixture of syn- and anti-forms, were subjected to a number of studies, including thermolysis,

hydrolysis, and reaction with aldehydes (to give di-imines). The metaphosphorimidates O=P(=NH)NH, and O=P(=NH)Cl have been postulated 5 2 as intermediates in the formation of imidopolyphosphates from the reactions of HCl with triaminophosphine oxide, (H2N)3P0. 48 49 5O

51 52

N. D. Bodnarchuk and V. 1. Kal'chenko, J . Gen. Chem. (U.S.S.R.), 1975, 45, 1007. A. S. Stepanek, L. M. Tochilkina, and A. V. Kirsanov, J . Gen. Chem. (U.S.S.R.), 1975,45,2085. G. B. Merrill and H. Schechter, Tetrahedron Letters, 1975, 4527. N. A. Nesmeyanov, 0.A. Rebrova, V. V. Mikul'shina, P. V. Petrovsky, V. 1. Robas, and 0.A. Reutov, J. Organometallic Chem., 1975, 110, 49. L. Reisel and R. Somieski, Z . anorg. Chem., 1975, 415, 1.

21 3

Phosphazenes

3 Properties of Acyclic Phosphazenes Halogeno-derivatives.-N-Chloroalkylphosphazenes undergo reactions with tricyanomethylsodium at the carbon, rather than at the phosphorus atom:53

+

RCClzN=PC13 NaC(CN)3 +(NC)2C=CClN=CRN=PC13 (R = C1, CCh, CClzMe, or CClzPh)

+ NaCl

Other chloroalkylphosphazenesundergo thermal decomposition to give isocyanate~,~~ and not a mixture of isomers as previously reported: 120 "C

(CC13)2ClP=NCOCOCl+

- co

(CCl&C12PNCO

Large numbers of derivatives of N-acyl- and N-aroyl-phosphazenes RCON=PCl, have been prepared by reactions with sodium c a r b o ~ y l a t e and s ~ ~o x i m e ~They . ~ ~ are of the general types R1CON=P(C02R2)nC13-nand RCON=P(ON=Z)nC13-n (n = 0-2). The same substrates form bicyclic diphosphazenyl-derivatives RCON=P(NHZNH),P=NCOR (R = CCI, or aryl; Z = o-phenylene, p phenylene, or CH2CH2).s7 The mass spectra of trichlorophosphazenes C13P=NX (X = sulphamoyl, acyl, aryl, or alkyl) and cyclodiphosphazanes(C1,PNX) (X = alkyl) have been described in detaiL6* N.q.r. spectroscopy is proving useful for the study of chlorophosphazenes and their dimers in the solid state. Thus the temperature and pressure dependence of the 35Cln.q.r. frequencies in (CI,PNR), (R = Me or Ph) is diagnostic of axial and equatorial chlorine Activation parameters for molecular reorientation in Cl,P=NCCI,CCI, follow from the temperature dependence of the 35Cl n.q.r. signals.60 The same dependence yields potential barriers for rotation about the 62 C13P=NP(0)(CC13)2,61 and CI3P=N .COP=N bond in C13P=NCCl(CC13)2,61~ CF3 61 of 6.8, 5.1, and 6.2 kcal mo1-1 respectively. Tl Measurements have been made6, from the 35Cln.q.r. spectra of C13P=NR [R = CCI(CCI,),, P(O)(CCI,),, COCF,, SO,N=PCI,, SOzCI,or CCl,CCI,]. 53

54 55 56 57

58 59

60 61

62 G3

N. G. Pavlenko and V. P. Kukhar', J. Gen. Chem. (U.S.S. R.), 1975, 45, 2058. l?. S. Kozlov, S. N. Gaidamaka, and L. I. Samarai, J. Gen. Chem. (U.S.S.R.), 1974, 45, 458. V. P. Rudavskii, D. M. Zagnibeda, M. N. Kucherova, and L. N. Sidlova, Farm Zhur. (Kiev), 1975, 30, 43 (Chem. Abs., 1976, 84, 164356). V. P. Rudavskii, D. M. Zagnibeda, and L. N. Sidlova, Farm Zhur. (Kiev), 1975, 30, 34 (Chem. Abs., 1976, 84, 105148). V. P. Rudavskii, D. M. Zagnibeda, and M. N. Kucherova, Farm Zhur. (Kiev), 1975, 30, 47 (Chem. Abs., 1975,83, 28205). C. Glidewell, Znorg. Chim. Acta, 1976, 18, 51. W. H. Dalgleish and A. L. Porte, J. Magn. Resonance, 1975, 20, 359. V. A. Mokeeva, I. A. Kyuntsel', and G. B. Soifer, Zhur.fit. Khim., 1975,49,1020 (Chem. Abs., 1975, 83, 57634). I. A. Kyuntsel', V. A. Mokeeva, G. B. Soifer, and 8. S . Kozlov, Spectroscopy Letters, 1975,8, 113. I. A. Kyuntsel', V. A. Mokeeva, G. B. Soifer, 8. S. Kozlov, and M. I. Povolotskii, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1954. I. A. Kyuntsel', V. A. Mokeeva, G. B. Soifer, and I. G. Shaposhnikov, J. Magn. Resonance, 1975, 20, 394.

8

0rganophosphorirs Cheinistry

214

The energies of absorptions observed in the U.V. spectra of the phosphazenes R13P=NCR2=C(CN)2 (R1= Ph, R2 = H, C1, or CC13; R1 = C1, R2 = C1 or CCl ,) have been compared with energies obtained from molecular orbital calculations.64 Amino-, Alkyl, and Aryl Derivatives.-Although few results on the synthesis of new phosph(1n)azenes have appeared, the reactions of this interesting group of compounds have been of particular interest. It has now been found that (Me,Si),NP= NSiMe,, the first phosph(r~~)azene to be isolated, undergoes slow dimerization at ambient temperatures. The crystal structure of this dimer, [(Me,Si),NP=NSiMe,],, has been e~tablished.~~ The ring is planar and the silylamino-groups adopt a mutual trans-orientation, with considerable steric crowding affecting the bond angles at nitrogen in these amino-groups. The reactions of the monomer (Me,Si),NP= NSiMe, with halogen compounds have been studied in detail (typical results are shown in Scheme 5).6s Br

\

RNR

/p\ RN, ,NR

RNHP\ Br

cl

/p\

RN\

,NR

cBl

aI

c1

I

R,NP=NR

I

I

Et

(R = SiMe,) Reagents: i, Brz; ii, BCb; iii,

ccb;ivy EtI; v, SiCL; vi, GeC14; vii, Sic14 or Clz. Scheme 5

The products of oxidation of (Me,Si),NP=NSiMe, with sulphur and with the diazo-compound (CF3),CN2 have not been isolated, since they readily undergo addition with the starting material to give cyclodiphosphazanes (Scheme 6).67 Closely related observations have also been reported; (30),6*(31),69 (32).'O 64 65 66 67

68 69

7O

V. V. Pen'kovskii and A. A. Kisilento, Teor. i eksp. Khim., 1975,11,807 (Chem. Abs., 1976,84, 89 380). E. Niecke, W. Flick, and S. Pohl, Angew. Chem. Internat. Edii., 1976, 15, 309. E. Niecke and W. Bitter, Chem. Ber., 1976, 109, 415. E. Niecke and W. Flick, J . Organometallic Chem., 1976, 104, C23. R. Appel and M. Halstenberg, J . Organometallic Chem., 1975, 99, C25. R. Appel and M. Halstenberg, Angew. Chem. Internat. Edn., 1975, 14, 769. R. Appel and M. Halstenberg, Angew. Chem. Internat. Edn., 1975, 14, 768.

Phosphazenes

215

R,NP =NR

-%

R,NPN,C(CF,),(=NR)

N ‘’

R,NP=NR

i

+ Me,S=NR

R,NP (=NR)~ Or

R,NP=NR

+ Ph,P=NMe

-

Me,S

NR

R2Np/N\p//

I

8\p/ NR ’ \

\N/ R

NR,

(31)

-+

[

MeN=P<

(R = SiMe,)

I:

+ Ph,P

(32)

Returning to the phosph(v)azenes, the reactions of Ph,P=NH with various acid halides have been examined in some detail :71 Ph3P=NH

+ XCI +Ph3P=NX + Ph$NH2

[X = Me, COYPhCO, SO2t0l-p~PhZP(S)CI, or PhzP] 71

M. Biddlestone and R. A. Shaw, J.C.S Dalton, 1975, 2527.

C1-

216

Organophosphorus Chemistry

The Ph3P=N- group can produce a strong deactivating effect, and where more than one chlorine atom is to be replaced by these groups in the same molecule, difficulties can arise. For example, reactions with PhP(S)CI2and with C3N,C13gave only PhP(S)CIN=PPh3 and C,N,CI(N=PPh,), re~pectively,~~ although there seems to be no difficulty in obtaining (Ph3P=N)3P0 and (Ph,P=N),PhPO by this route.72 Phosphorus(1n) chlorides do not always give simple products. Thus it was not possible to obtain PhP(N=PPh3)2 by this 72 and PhPC12and Ph,P=NSiMe, gave PhP(N=PPh3)2Me3SiC1.72 The trimethylsilyl-phosphazeneis useful in reactions with Pc13:72

+

PC13 3Ph3P=NSiMe3 -+ (Ph3P=N)3P P(NMe2)3 3Ph3P=NH +(Ph3P=N)3P

+

+ 3MeaSiCI + 3MezNH

Phosphazenes of the type R1R22P=NH (R1 and R2 = alkyl or aryl) readily add to trihalogenoacetonitriles:

+

R1R2zP=NH (X = F or Cl)

X3C. CN +R1R2zP=NC( =NH)CX3

There have been several reports of reactions which involve cleavage of the Si-N bond in N-silylphosphazenes.Thus Et3SiX (X = F or C1) can be used to prepare triethylsilyl-derivativesby trans-silylation:73 AlkaP=NSiMes

+

+

EtsSiX +Alk3P=NSiEts

Me3SiX

Disilanyl-derivatives(33) 74 and (34) 76 may be obtained in a similar way. The series Alk3P =NSiMes

+

Alk3P =NSiMe3

CISiMezSiMezCl+

+

ClSiMezSiMes

+

Alk3P=NSiMezSiMe2C1 Me3SiCl (3 3) Alk3P =NSiMezSiMes + Me3SiCl (34)

(34) of silyl-derivativeshas also been obtained by the reactions in Scheme 7.75 Alk,P=NSiMe,SiMe,Cl

Alk,J?= NLi Alk,P

+

LiMe

\

+

ClSiMe,SiMe,

f

N,SiMe,SiMe, Scheme 7

7

Alk,P=NSiMe,SiMe, (34)

Other reactions include insertion of SO3 into the Si-N phosphazenyl-derivatives (Scheme 8).76 R1R2zP=NSiMe3

i __+

bond and formation of di-

iii

R1R22P=NS02 * OSiMe3 -ii

-1

__+

R*=Ph, Ra=Me

R1R22P=NS02 * O H + (Me3Si)zO (R1 = Me, R2 = Ph; R1 = P h , R 2 = M e o r P h )

(PhMezP=N)2SOz

+

(Me3Si)zO

+

H2O

Reagents: i, SO3; ii, HzO; iii, PhMezP=NH.

Scheme 8 A. S. Stepanek, V. A. Zasorina, I. N. Zhmurova, and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1012. W. Wolfsberger, 2. Naturforsch., 1975, 30b, 900. r4 W. Wolfsberger, Z. Naturforsch., 1975, 30b, 904. 75 W. Wolfsberger, 2.Naturforsch., 1975, 30b, 907. 7 6 R. Appel, I. Ruppert, and M. Montenarh, Cliern. Ber., 1976, 109, 71.

72

73

217

Phosphazenes

A cyclic product (35) incorporating the SO2group was prepared, but this could not be achieved when the phosphazenyl groups were further separated, when (36) was produced instead.

(CH2)2(Ph2P=NSiMe&

+

+ (Me3Si)zO

SO3 -+ (CH&(Ph2P=NSO20H)2 (36)

Another reagent that may be used to effect insertion into the Si-N bond is trichloroacetaldehyde, to give (37).77A series of derivatives of triphenylphosphazenyl(RO)z(MesSiO)P=NSiMes

+

CC13CHO --+ (RO)z(MesSi)P=NCHCC130SiMe3 (37)

(R = Meor Et)

sulphamoyl chloride has been prepared by reactions with alcohols in pyridine, or amines in chloroform solution (Scheme 9).78

Ph,P=N

SO, Cl

Ph3P= NS0,NR'R'

Y Y k

Ph3P=N

SO, OR3

R' = H, R2 = alkyl or aryl; R' = R2 = alkyl; R3'= alkyl or aryl Reagents: i, R1R2NH; ii, R 3 0 H .

Scheme 9

The role of phosphoramidates and phosphazenes as N,O-ambident nucleophiles has been c~nsidered.'~ Thus in the reaction of (EtO),P=NCOPh with hydrogen chloride it appears that nitrogen rather than oxygen undergoes protonation : (Et0)3P=NCOPh

+

HCl -+ (Et0)2P(O)NHCOPh

+

EtCl

No reaction occurs with MeI, or with Me,SiCl. Thermally induced rearrangements of phosphazenes to phosphoramidates (38) 8o and (39) have also been reported. (CH2=CHCH20)(Et0)2P =NN=CHCOzMe + (CH2 =CHCH20)(EtO)P(O)NEtN =CHCOzMe (3 8)

(R0)2P( =NPh)OCsBreOH-p

(R = Me or Et) 77 78 79 8O

R1

+(RO)(PhNH)P(0)OCsBr40R-p (39)

L. V. Nesterov and N . E. Krepysheva, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1975, 2846 (Chem. Abs., 1976,84, 105683). D. E. Arrington, Znorg. Chem., 1975, 14, 1236. C. Glidewell, J . Organometallic Chem., 1976, 108, 335. R. D. Gareev and A. N. Pudovik, J . Gen. Chem. (U.S.S.R.), 1975, 45, 1860. A. N. Pudovik, 8. S. Batyeva, and V. A. Al'fonsov, J . Gcn. Chem. (U.S.S.R.), 1975,45, 2366.

218

Organophosphorus Chemistry

The formation of (39) provides examples of a rearrangement where the rate is related to the acidity of the phenolic proton. N-Arylphosphazenes Ph3P=NC6H4X-p(X = H, Me, hal, or NOz) form adducts with stannic chloride in which the P-N absorption in the i.r. spectra near 1300 cm-l disappears.s2From this it was inferred that the donor atom is nitrogen and that the P-N bond order is reduced. The phosphazene Ph,P=NPh undergoes preferential metallation by phenyl-lithium in the ortho-positions of a P-phenyl group, probably because lithium can be complexed intramolecularly by the phosphazene nitrogen atom in this position.83In the P-alkyl-substituted derivatives Ph2RP=NPh (R = Me or Bun) metallation occurs at the a-carbon atom. R

N

0

Ph,P=NR

i-

Ph/\

-+ Ph,PO

+Y h A

A convenient new synthesis of aziridines (40)from oxirans and phosphazenes has

'

0 been r e p ~ r t e d In .~~ reactions with the oxiran Ph0CH2,' intermediates such as (41) have been identified, which decompose thermally to give aziridines and

R

Ph3P0. N-Aziridinylphosphazenes react with isocyanates and with aroyl compounds (Scheme Numerous reactions have also been carried out with

"aph R'

Ph,P=N

RN=C=N*NI

R!

'--, Ph

+'Ph3P0

Phxc=N-N(l

Ph

+ Ph,PO

Ph

R' = H or Ph; R2 = alkyl or aryl; X = Br, CN, or N, Reagents: i, R2NCO; ii, PhCOX.

Scheme 10 82

83 84

85

N. A. Ivanova, V. A. Kogan, 0. A. Osipov, N . I. Dorokhova, and A. A. Shvets, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2666. C. G. Stuckwisch, J . Org. Chem., 1976, 41, 1173. R. Appel and M. Halstenberg, Chem. Ber., 1976, 109, 814. J. Schweng and E. Zbiral, Tetrahedron, 1975, 31, 1817.

219

Phosphazenes keteqss which also provided a route to nitrifes, e.g. PhzC=C=O

+ Ph3P=N*NR1R2+Ph2C=C=N*NR1R2 +

PhsPO

Ph2C(CN)NR1R2

The reactions of Ph3P=NC6H4X-p(X = NH2 or N=PPh,) with dimethyl acetylenedicarboxylate have been des~ribed.~' Photolysis of phosphazenes ArylSN=PPh, did not yield nitrenes (as indicated by lack of reaction with nitrene-trapping agents), but disulphides ArS - SAr, triphenylphosphine, and tarry materials.12Substituenteffectsin N-aryl-, N-(triarylmethy1)-,and N-(triarylsily1)-phosphazeneshave been investigated by 9Fand 31Pn.m.r. The triarylmethyl derivativessuch as Ph,CN=PPh, were prepared by the reaction of Ph,P=NH with Ph,CCI and the silyl-compounds by the azide route.88 l9F N.m.r. shifts of phosphazenes Ar1Ar2Ar3P=NC6H4Fwere related to effects observed in the U.V. Structure and bonding in the amides R1R2NCON= spectra of these R2 included H, D, and Me) have been discussed in relation to the i.r. and PPh3 (R1, 31Pn.m.r. spectra of these corn pound^.^^ The auxochromic action of aryl-substituted 92 phosphazenes continues to be a source of

4 Synthesis of Cyclic Phosphazenes Yet more improvements in the synthesis of chlorocyclophosphazeneshave appeared. Yields in the PC15-NH4Cl reaction are increased by the use of heavy-metal salts as catalystsYg3 but similar results may also be achieved by the use of acid-treated montmorillonite clay.94The use of surfactants can also improve yields of cycIic products.95 The new phosphazene triazene hybrid ring compound (42) can be obtained from cyanamide by two slightly different routes, A g6 and B 9 7 (Scheme 11). Substitution of ammonia in route B leads to further ring compounds (43) and (Ma, b).97 Methylcyclophosphazenes N3P3Me6 and N,P,Me are more conveniently prepared and separated using methylamine hydrochloride, rather than ammonium chloride, in the reaction with Me2PC13.98The initial product from this reaction is probably (Me,PClNMe),, which on pyrolysis gives a mixture of N,P,Me, * MeCl and 86 87 88 89

91

92 93 94

95

96 97 98

J. Schweng and E. Zbiral, Monatsh., 1976, 107, 537. E. M. Briggs, G. W. Brown, W. T. Dawson, and J. Jirecny, J.C.S. Chem. Comm., 1975, 641. S. Yolles and J. H. R. Woodland, J . Organometallic Chem., 1975, 93, 297. I. N. Zhmurova, V. G. Yurchenko, R. 1. Yurchenko, E. V. Konovalov, and Yu. P. Egorov, J . Gen. Chem. (U.S.S.R.), 1974, 44, 2375. W. Buder and A. Schmidt, Spectrochim. Actu, 1975, 31A 1813. I. N. Zhmurova and V. G. Yurchenko, J. Gen. Chem. (U.S.S.R.), 1975,45, 1924. R. I. Yurchenko, I. N. Zhmurova, and A. I. Sedlov, J . Gen. Cliem. (U.S.S.R.), 1975, 45, 1705. H. Kodama, T. Kodama, M. Senoura, K. Kuda, and H. Aoyama, Japan. Kokai 75 33033 (Chem. Abs., 1976, 84, 121 516). D. Hardy, U.S.P. 3869540 (Chem. Abs., 1975,82, 142252). H. Maki and T. Haitaka, Japan. Kokai 75 43097 (Chem. Abs., 1975,83, 100256). E. Fluck, E. Schmid, and W. Haubold, 2. Nuturforsch., 1975, 30b, 808. R. Taubert, Ger. Offen. 2405399 (Chem. Abs., 1975, 83, 206337). R. T. Oakley and N. L. Paddock, Cunad. J. Chem., 1975, 53, 3038.

220

Organophosphorus Chemistry

N4P4Me,.2MeCl. These can be separated, taking advantage of the solubility of the former compound in acetonitrile. N3P3Me6Is then generated in high yield by the controlled pyrolysis of N3P3Me6* MeCI. 5 Properties of Cyclic Phosphazenes Halogeno-derivatives.-Chlorocyclophosphazenes (NPC12)4-7or bromocyclophosphazenes ( N P B I - ~ )can ~ , ~ be used to advantage in tungsten-cycle incandescent lamps.g9Thin-layer chromatography may be used loo to separate the homologous series of chlorocyclophosphazenes (NPCl,) 3-7. Spectroscopic studies of halogeno-derivatives are limited to the vibrational spectralo1of the series N3P3C16,N3CP2C15,g6 N3C2PC14,and N3C3C13,as well as N3P3C16NHPri,lo2 and (45).lo3The pressure-dependence 35Cln.q.r. work on in the case of the isopropylamino-derivative enables a discrimination to be made between the two kinds of chlorine atoms in the -PCl, groups.1o2

Halogen-replacement reactions on N3P,C16which entail the use of heterogeneous reaction conditions are speeded up, and yields improved, when the crown ether 18-crown-6 is used as a cata1y~t.l~~ Thus K F and KCNS gave N3P3F8 and NsP~(SCN)~ respectively, but KBr and KCN gave NP,Brg and thermally unstable N ,P,Cl SNC. 99 R. B. Johnston and J. M. Rees, U.S.P. 3898500 (Chem. A h . , 1975, 83, 156811). loo V. Novobilskf, V. Kolsky, and W. Wankk, Z . anorg. Chem., 1975, 416, 187. l o 1 J. Weidlein, E. Schmid, and E. Fluck, 2.anorg. Chem., 1976, 420, 288. l o 2 W. H. Dalgleish, R. Keat, A. L. Porte, and R. A. Shaw, J. Magn. Resonance, 1975, 20, 351. Io3 E. A. Romanenko, Teor. i eksp. Khim., 1975, 11, 705 (Chem. A h . , 1976, 84, 104617). 104 E. J. Walsh, E. Derby, and J. Smegal, Inorg. Chim. A d a , 1976, 16, L9.

221

Phosphazenes

Amino-derivatives.-Thermodynamic ammonia and red phosphorus: 4NH3

+

aspects of the synthesis of phospham from 2P+2PN2H

+ 5Hz

have been investigated.lo5At temperatures above 500 "C,equilibrium was established within a few hours. It appears that the phospham so produced can be converted into aminocyclophosphazenes by reaction with ammonia at high pressures:

The aminophosphazenes are still of interest as fertilizers with a high PN content lo6,lo7 and they impart improved flame resistance to cellulosic materialslo8and phenolformaldehyde resinslog(see also Section 7). Other aspects of their chemistry have been reviewed.l1°

Cyclization at a geminal diamino-group can be effectedll1 by the dichlorosilane, MeHSiCl, to give (46). A closely related geminal-diamino-compound is the precursor of a bisphosphazeny 1-derivative:

Chlorocyclophosphazenes are not particularly reactive towards silicon-nitrogen compounds, but the spirocyclic compounds (47) have been prepared .ll, An interesting development in the chemistry of aminocyclotetraphosphazenes is the formation of bicyclic structures. In the first example113the phosphazene ring is 105

106 107 log 109

J. M. Sullivan, Znorg. Chem., 1976, 15, 1055. W. Waniik, Pure Appl. Chem., 1975,44,459. A. P. Conesa, Compt. rend. Acad. Agric. France, 1974, 60, 1353. A. M. Evteev, M. A. Tyuganova, Z. A. Rogovin, and V. V. Kireev, Khim. Voloknu, 1975, 31 (Chem. A h . , 1976,84,60985). Yu. P. Belyaev, M. S. Trizno, and A. F. Nikolaev, Plast. Massy, 1975,7 (Chern. Abs., 1975,83, 11241).

R. Vilceanu, V. Eliu-Ceasescu, D. Ene, P. Schultz, Z . Szababai, and N. Vilceanu, Pure Appl. Chem., 1975,44, 285. 111 M. Kajiwara, M. Makihard, and H. Saito, J. Znorg. Nuclear Chem., 1975, 37, 2562. 112 G. S. Gol'din, L. S. Baturina, A. N. Novikova, and S. G. Federov, J. Gen. Chem. (U.S.S.R.),

110

1975,45, 2525. 113

H.W. Roesky and E. Janssen, Angew. Chem. Ztiternat. Edn., 1976, 15, 39.

222

Organophosphorus Chemistry R R ,N-- X, N-X AN / \ N,P3C1, t MezS;l ,CHz -+ c1,P’ ‘P

FH2f Me,SiCI,

H N-N Me

‘+p/NE-Ee

(R = Me, X = CH,; R = H, X = CH,NMe)

spanned by a sulphur di-imido-groupto form (48). The second example is formed in the reaction of 2,6-N4P4C16(NHEt),with dimethylamine in chloroform solution to form (49).l14 The crystal structure of (49) (see Section 8) reveals that the bridging P-N bonds are very long, and that the bridge nitrogen atom has considerable sp3 character.

The importance of steric effects has been emphasized in understanding the reactions of N3P3Cl,with dibenzylamine and ben~ylarnine.~~~ This is particularly true of reactions with the former amine, which gave only two derivatives,N3P3C1,N(CH,Ph), and non-geminal N3P3C1,[N(CH,Ph),],. The remaining chlorine atoms in these derivatives can, however, be selectively replaced by dimethylamino-groups. These products include N3P3C1N(CH2Ph)2(NMe2)a, the first example of a stable pentaaminomonochloro-derivative, in which reactions at the =PClN(CH,Ph) group are sterically hindered. Benzylamine is, as expected, more reactive, and gives a series of derivatives N3P3Cl,-,(NHCH,Ph)n, n = 1, 2 (two isomers), 4, and 6. Structures were established by lH n.m.r. spectroscopy and by the preparation of mixed benzylamino-dimethylamino-derivatives. Interestingly, the non-geminal isomer predominates when n = 2, but the n = 4 isomer has a geminal structure. The reaction of N3P3CI, with the N-sodio-derivative NaNMeP(O)(OEt), gives a series of derivatives N3P3Cl,-,[NMeP(0)(OEt)2]n, n = 1, 2 (non-geminal), and 3 (surprisingly, gemina1),l16 the structures of which were established by IH and 31P n.m.r. The fluorination of NpP4Cl,(NMe,), and N4P4C15(NMe3)3 114

T.S.Cameron, Kh. Mannan, S. S. Krishnamurthy, A. C. Sau, A. R. Vasudeva-Murthy, R. A.

113 116 117

Shaw, and M. Woo Is, J.C.S. Chem. Comni., 1975, 975. M. U1-Hasan, R. A. Shaw, and M. Woods, J.C.S. Dalton, 1975, 2202. P. Gehlert, H.Schadow, H. Scheler, and B. Thomas, 2. anorg. Chem., 1975, 415, 51. B. Thomas, P. Gehlert, H. Schadow, and H. Scheler, 2. anorg. Chem., 1975, 418, 171.

223

Phosphazenes

by KSO,-KF results in the formation of isomeric mixtures of N4PpF6(NMe2),and N4P4F5(NMe,), respectively.l18 Fluorination of dimethylamino-derivatives of N,P,Cl, by the same reagent only occurs at =PC12 centres. Tris(trimethylstanny1)amine reacts readily with fluorophosphazenes with cleavage of the Sn-N bond:119 e.g. N3P3F6

+ (Me3Sn)sN +N3P3FsN(SnMe& +

Me3SnF

similar reactions occur with N4P4F8119 and N5P5Flo.120 Subsequent reactions with ClMe,SiN=S=NSiMe,Cl gave (5O)llg and with (51) gave (52).120 By contrast,

(50)

(X = N o r NI;;P==N)

(52) (X = NorNF,P=N)

N,P,F,N(SnMe,), gives what may be N,P,F,N=S=NSMe with the same reagent ( 5 1).lZo Basicity measurements have been employed to demonstrate that protonation can occur on endocyclic or exocyclic nitrogen atoms in an extensive series of triphenylphosphazenyl-derivatives of N ,P ,CI, .lZ1Ring protonat ion occurs when (Ph ,P=N)X k (X = C1 or Ph3P=N) groups are present, and exocyclic protonation when (Ph,P=N)XP- (X = NH2, NMe,, or Ph) groups are present. Crystallographic work suggests that the latter behaviour can be correlated with a preferred conformation in which the plane containing the exocyclic P-N-P unit is perpendicular to the phosphazene ring (53). Ring protonation, and better electron transfer to the phosphazene ring, occurs when the Ph3P=N- group in (53) is turned through approximately 90"(see also ref. 1).

Alkoxy- and Ary1oxy-derivatives.-The results of a complete study of the replacement of chlorine in N3P3C16by trifluoroethoxy-groups have appeared.lZ2Sodium trifluoroethoxide gives the series N,P3CI,-n(OCH,CF,)n, n = 1, 2 (two isomers), 3 (two isomers), 4 (two isomers), 5, and 6, and the structures of those derivatives where n = 2, 3, and 4 were established by n.m.r. spectroscopy. Dipole moments were not very useful for distinguishing isomers. The reaction follows a predominantly trans-non-geminal pathway, and the authors suggest that this may be accounted for 118 119 120 lzl

122

D. Millington and D. B. Sowerby, Phosphorus, 1974, 5, 51. H. W. Roesky and B. Kuhtz, Chem. Bcr., 1975, 108, 2536. H. W. Roesky and E. Janssen, Chern. Ber., 1975, 108, 2531. S. N. Nabi, M. Biddlestone, and R. A. Shaw, J.C.S. Dalton, 1975, 2634. J. L. Schmutz and H. R. Allcock, Inorg. Chem., 1975,14, 2433.

224

Organophosphorus Chemistry

in terms of steric effects. Sodium trifluoroethoxide has also been used to effect the replacement of chlorine in trans-N3P3C14(NMeJ2 :123

In N3P3C1,(NMe,),(OCH,CF3), both trifluoroethoxy-groups are bonded to the same phosphorus atom, but it is not clear whether this is the result of steric control also. The structures of the fluoroalkoxy-derivatives N3P3C16-n(OCH2C,F5), (n = 2, 3, or 4), reported previously, have now been shown by 31Pn.m.r. spectroscopy to be n0n-gemina1.l~~ The same technique was used to show that N3P3C14[OCHp(CF2)3CH20] has a spiro-structure (54). A mixture of trimeric and tetrameric heptafluorobutoxy-derivatives (55) has been obtained.126

(54)

(XCH20)XPNH2

CI, __+

Et,N

(XCH20)XPNH2C12--+ [(XCHaO)XPN]3,4 (55 )

tX = C3F7)

The preparation of alkoxy-derivativesof cyclic phosphazenes such as N3P3(OPrn), has been described in two patents,lZstl Z 7and alkoxyphosphazenes [NP(OAIk),],,,, have been separated by g . l . ~ . l ~ ~ Fully substituted phenoxy-derivatives of cyclophosphazenesN3P3(OC6H4-X-p)6 (X = CI, F), N3P3(OCgF6)6, N ~ P ~ ( C ~ H ~ - D - Pand ) B , N4P*(OC6F5)8 have been prepared by reactions with the respective sodium p h e n o x i d e ~ The . ~ ~ ~phenoxide N3P3(OPh),was subjected to a series of reactions with electrophilic reagents which may be summarized: X+

N3PdOPh)6 +N~P~(OCS&X-P)G (X = NOz, C1, or Br) Hydrolysis of these compounds only starts in alkali at 140-160 "C, to give products which are probably present as a mixture of tautomeric forms (56) and (57). Detailed consideration has been given to the role of intermediates in the degradation of M. A. Andreeva, L. M. Gil'man, A. S. Lebedeva, V. V. Korshak, and S. V. Vinogradova, J . Gen. Chem. (U.S.S.R.), 1975, 45, 1261. 124 V. N. Sharov, V. N. Prons, V. V. Korol'ko, A. L. Klebanskii, and G. P. Kondratenkov, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1919. lZ5 V. N. Prons, M. P. Grinblat, and A. L. Klebanskii, J . Gen. Chem. (U.S.S.R.), 1972, 45, 2380 126 J. T. F. Kao, U.S.P. 3939228 (Chem. Abs., 1976, 84, 164146). lZ7 R. Wurmb, D. Werner, G . Wunsch, V. Kiener, and W. Schwarz, Ger. Offen. 2333 746 (Chem. Abs., 1975, 82, 157768). 128 P. Schultz, R. Vilceanu, and D. Ciubotaiiu, J. Chromatog., 1975, 111, 438. 129 P. 0.Gitel', L. F. Osipova, and 0. P. Solovova, J . Gen. Chem. (U.S.S.R.), 1975, 45, 1714. 123

225

Phosphazenes ArO, N//P' ArO 'P,

ArO,

,OAr

I

f;' OH +AIO,

P' 'OAr

ArO"N'

,ho

N ~ \ N H

,P'

I

ArOY'N

(56)

,P/

I/o

(57)

[Ar = C,H.,Xp(X = H, F, 01Cl)]

N3P3C16to phosphoranes by ortho-dinucleophiles such as o-aminophenol and catech01.l~~ Thus it has now been shown that the intermediate (58), in the formation of (59), can be isolated from reactions with the former dinucleophile, but (58) is more conveniently isolated from the reaction of non-geminal N3P3C1,(NMe,), with o-aminophenol.

Reactions with several other dinucleophiles have been studied. These include NaOC,H&H,OH-o, which gives N,P,(OC,H*CH,OH-o)nCl6-la (yt = 2, 3, 4, 6), the latter of which was the precursor of a condensation p01ymer.l~~ Salicylic acid in the presence of triethylamine gives (60), which can be sublimed to give (61).132Aliphatic and aromatic aldoximes can be converted into nitriles by reaction with

130 131

132

H. R. Allcock, R. L. Kugel, and G. Y. Moore, Inorg. Chem., 1975,14, 2831. M. ICajiwara and H. Saito, Polymer, 1975, 16, 1. W. J. Walsh and E. Derby, Inorg. Chim. Acra, 1975, 14, L40.

226

Organophosphorus Chemistry

N3P3C1, (Scheme 12).133The rnass,l3*lH, and 31Pn.m.r. alkoxychlorophosphazenes have been described. i, ii

RlRZC(OH)RW=N * OH __+ R1RzC =0 Reagents: i, Et3N; ii, N3P3C16.

of polycyclic

+ R3C = N

Scheme 12

N3P3C1, and DMSO undergo a complex series of reactions leading to phosphoramidic acids (Scheme 1 3).136 N3P3C13(OH),was isolated and characterized as its i

N3P3C16

__+

[N3P3C15DMSO]+CI-+N3P3(0H)C15

+

ClCHzSCH3

-li

i

N3H3P303(OH)3.CICH2SCH3+N3P,&13(OH)3. ClCH2SCH3 Reagent: i, DMSO.

Scheme 13

trifluoroethoxy-derivative N3H3P303(OCH2CF3)3;[NPF2I3and and N4P4CI8 were subjected to a similar series of r e a ~ t i 0 n s . lThe ~ ~ acid N3P3(OH),(OPh), has

Reagents: i, CCL; ii, K ; iii, heat; iv, (63); v, C4HgLi.

Scheme 14 133 134

135 136

G. Rosini and A. Medici, Synthesis, 1975, 665. H. Rose and H. Specker, Z. analyt. Chem., 1975,273,425 (Chem. Abs., 1975, 83, 70879). H. Manns and H. Specker, 2. analyt. Chem., 1975, 275, 103 (Chem. Abs., 1975, 83, 88129). E. J. Walsh, S. Kaluzene, and T. Jubach, J. Inorg. Nuclear Chem., 1976, 38, 397.

Phosphazenes

227

been used for the extraction of the actinides plutonium(Iv, VI), neptunium(Iv, VI), and uranium(v1) from aqueous The use 138 of non-geminal N3P3F4(SMe)2,geminal N3P3F2(0Me)*,and N3P3FSX [X = N=CMeSP(O)(OEt),, NHCO,Me, and NHNHMe] as insecticides has been suggested. The structural assignments to the first two compounds are somewhat surprising. Alkyl and Aryl Derivatives.-Compounds of this type are limited to the synthesis of a second bis(cyclotriphosphazeny1)-derivative [Scheme 14, compound (62)] containing a P-P bond.139The crystal structure of (62) confirmed the presence of a P-P bond (see also Section 8). It is known that compound (64) is methylated by methyl iodide.

By contrast, compounds (65) undergo methylation at the nitrogen atom to give (66).140The quaternary salts (66) were also isolated with BPh4- or SbC1,- anions.

(65) (X = Y = Me; X = Me, Y = NH,; X = Y = NH,)

(66)

6 Polymeric Phosphazenes Some indication of the increasing importance of this topic is provided by the number of review article^.^^^-^^^ The formation of essentially linear polymers from N3P3CI, and/or N,P,CI 8 is catalysed by and by (CF3S03)2Hg.148Torsional braid analysis on 137 138 139 140 141

142 143 144 145

146

147

148

D. I. Skorovarov, E. I. Filippov, V. V. Shatalov, V. A. Belov, and G. G. Arkhipova, Radiokhimiya, 1976,18,29 (Chem. Abs., 1976, 84, 196295). H. Adolphi, G. Wunsch, and V. Kiener, Ger. Offen. 2334917 (Chem. Abs., 1975,82,156392). A . Schmidpeter, J. Hogel, and F. R. Ahmed, Chem. Ber., 1976, 109, 1911. A. Schmidpeter and H. Eiletz, Chem. Ber., 1976, 109, 2340. G . Pezzin, M. Osellame, L. Busulini, and 1,. Silvano, Chimica e Zndustrin, 1976, 58, 12 (Chem. Abs., 1976, 84, 106095). E. Kobayashi, Shikizni Kyokaishi, 1975, 48, 460 (Chem. Abs., 1975, 83, 164594). M. Kajiwara, Purasuchikkusu, 1975, 26, 63 (Chem. Abs., 1975, 83, 97962). I. Sakurada, Kobunshi Kako, 1975, 24, 356 (Chem. Abs., 1976, 84, 165211). H. R. Allcock, U.S. N.T.I.S. A.D. Rep., 1975, AD-A013537 (Chem. Abs., 1975, 84, 17797). D . P. Tate, Rubber World, 1975, 172, 41. H. R. Allcock, K. M. Smeltz, and J. E. Gardner, U.S.P., 3937790 (Chem. Abs., 1976, 84, 122 595). K. A. Reynard and A. H. Gerber, Ger. Offen. 2517142 (Chem. Abs., 1976, 84, 9Q797).

228

Organophosphorus Chemistry

(NPC12)n149and on (NPX& (X = F, C1, Br, or NCS)150 has given molecular weight and other information, and 31Pshifts of (NPX& (X = F, CI, Br, or NCS) have been determinedl5l on samples in the solid or solvent-swollen state. Some of the properties of polymers derived from (NPC12)nand a l a n i ~ ~and el~~ from a r y l a m i n e ~ have l ~ ~ been described. The former are water-soluble and have potential medical applications. Molar refraction and volume data on NP(NHC,(R = H, Me, OMe, or C1) have been determined.154 Of the alkoxy-substituted polymers, [NP(OCH2CF3)2]nstarts to depolymerize155 at 150 "C, and [NP(OPr*),], has been suggested as a flame retardant for rayon.156 Polymers of the latter type are decolorized by 0z0ne.l~~ Some of the thermomechanical properties of fluoroalkoxy-polymers have been described 158 and when compounded with silica or aluminium silicate they have aircraft seal app1i~ations.l~~ Elastomers which are fluoroalkoxy copolymers and terpolymers have been synthesized,160 and the cross-linking of these polymers with peroxides 161 or di-isocyanides16zis possible. Various aspects of the 16* properties,ls5 and purification of aryloxy-substituted polymers have been the subject of patent applications. These materials also improve the flame resistance of rayon.167 Of a series of phenylhalogeno-cyclotriphosphazatrienes,only N3P3F5Phformed a homopolymer on heating.lss Ammonia can be usefully employed to effect the removal of hydrogen chloride in the condensation of polyols with (NPC12)n.1e9

149

T.M.Connelly and J. K. Gillham, J. Appl. Polymer Sci.,1975, 19, 2641.

N. Buchholtz and H. Specker, Naturwiss., 1975, 62, 530. H.-G. Horn and H. C. Marsmann, Makromol. Chem., 1975, 176, 1359. 152 H. R. Allcock, K. M. Smeltz, and D. P. Mack, U.S.P. 3893980 (Chenz. Abs., 1975, 83, 148 095). l 5 3 J. E.White, R. E. Singler, and S. A. Leone, J. Polymer Sci., Polymer Chem. Edn., 1975, 13, 2531. 154 S. Lora, G. Pezzin, M. Osellame, and L. Busulini, Makromol. Chem., 1976, 177, 299 (Chem. Abs., 1976, 84, 106187). 155 H. R. Allcock and W. J. Cook, Macromolecules, 1974, 7, 284. l 5 6 R. Wnrmb, D.Werner, G. Wunsch, V. Kiener, and W. Schwarz, Ger. Offen. 2333746 (Chem. A h . , 1975, 83, 61 585). 157 V. C.Patel, U.S.P. 3839513 (Chem. Abs., 1975, 83, 60588). 158 T.M.Connelly and J. K. Gillham, J . Appl. Polymer Sci., 1976, 20, 473. 159 R. E. Singler, K. A. Rose, R. W. Sicka, J. C. Vicic, and S. H. Rose, New 2nd. Appl. Adcan. Mater. Technol. Nat. S.A.M.P.E. Symp. Exhib., 1974, p. 129 (Chem. Abs., 1975, 83, 61 174). I6O S. H. Rose and K. A. Reynard, U.S.P. 3888799 (Chem. Abs., 1975, 83, 148778). 161 G. S. Kyker and A. Antowiak, Ger. Offen. 2502333 (Chem. Abs., 1975, 83, 194877). 1 6 2 K.A. Reynard and S. H. Rose, U.S.P. 3844983 (Chem. Abs., 1975, 83, 60614). 1 6 3 K.A. Reynard and S. H. Rose, Ger. Offen. 2427479 (Chem. Abs., 1975, 83, 194113). 164 R. E. Singler, G. L. Hagnauer, N. S. Schneider, B. R. Liberte, R. E. Sacher, and R. W. Matton, J. Polymer Sci.,Polymer Phys. Edn., 1974, 12, 433. 165 G.L. Hagnauer and B. R. Laliberte, J. Polymer Sci.,Polymer Phys. Edn., 1976, 14, 367. 166 K. Nagai, H. Okada, I. Takeuchi, and Y.Nakamura, Japan. Kokai 75 82018 (Chew. Abs., 1975, 83, 206968). 1 6 7 H.Terazawa, T.Kondo, and T. S . Suganama, Japan. Kokai 74 125626 (Chem. Abs., 1975,82, 157 777). 168 H. R. Ailcock and G. Y . Moore, Macromolecules, 1975, 8, 377. 169 W.Walczyk, Z.Jedlinski, K. Brandt, and B. Haszczyc, Pol. P. 75951 (Chem. Abs., 1976, 84, 74889). 150

151

Phosphazenes

229

N,P,Cl,phenol 170 and N,P,CI,Ph,-dihydric alcohol 171mixtures have been used to form condensation polymers containing phosphazene rings. The same objective has also been achieved using N3P3C150Ph-aromaticdiamine,172geminal N3P3CI4Ph2aromatic diamine,l73 and N3P3(NHPh)2(OBut),-Ph,SiCI mixtures.l74 Relatively low molecular weight polymers include R1R2P(0)(N=PR1R2).PR1R20H(R1,R2 included alkyl, aryl, and a l k o ~ y and ) ~ ~phosphoramidic ~ acids from the hydrolysis of (NPC12).,176 the latter of which form hydrophobic materials.

7 Phosphazenes as Fire Retardants A big increase in the number of patent applications on this topic is apparent. The area has been r e v i e ~ e d ,and ~ ~it~is, clear ~ ~ ~that the alkoxycyclophosphazenesfind the widest range of applications, particularly in improving the flame resistance of rayon179-188and polyurethane^.^^^-^^^ Phenoxy-substituted phosphazenes have attracted less a t t e n t i ~ n . ~Oligomeric ~ ~ - ~ ~ ~ chlorocyclophosphazenes also have

K. Doi, H. Kawamura, and T. Maikuma, Japan. Kokai 74 37820 (Chem. Abs., 1975, 83, 165039). 1 7 1 A. A. Kudryshov, V. N. Kitaev, V. V. Kireev, and V. V. Korshak, Vysokomol. Soedineniya, 1975, 17, B, 246 (Chem. Abs., 1975, 83, 59450). 172 G. F. Telegin, V. V. Kireev, and V. V. Korshak, Vysokomol. Soedineniya, 1975, 17, A , 477 (Chem. Abs., 1975, 83, 79763). 173 M. Kajiwara and H. Saito, Angew. makromol. Chem., 1975, 42, 55 (Chem. Abs., 1975, 83, 164613). 174 M. Kajiwara, A. Sakamoto, and H. Saito, Angew. makromol. Chem., 1975,46,63 (Chem. Abs., 1976, 84, 60291). 1 7 5 V. V. Korshak, V. V. Kireev, A. A. Volodin, and S. N. Zelenetskii, Russ. P. 491 669 (Chem. Abs., 1976, 84, 60225). 176 B. N. Laskorin, E. A. Filippov, and D. I. Skorovarov, Russ. P. 497305 (Chem. Abs., 1976,84, 88923). 17' J. Cermak, R. Kopecny, J. Kroupa, J. Kunicky, and A. Novetny, Nehorlaoost. Plast. Hurot, Dreoa Text., 1974, 85 (Chem. Abs., 1975, 83, 80036). l i 8 M. Kajiwara, Sen-i Kako, 1975,27, 195, 319, 381, 507,631,693 (Chem. Abs., 1975,83,98955, 207416, 207420; ibid., 1976, 84, 32397, 91 421, 137022 respectively). 179 Ethyl Corporation, Belg. P. 824079 (Chem. Abs., 1976, 84, 123368). l a o C. W. Lanier and J. T. F. Kao, U.S.P. 3869294 (Chem. Abs., 1975, 82, 157662). 181 C. W. Lanier and J. T. F. Kao, Ger. Offen. 2427879 (Chem. Abs., 1976, 84, 61 097). 182 W. N. Knopka, U.S.P. 3866405 (Chem. Abs., 1975, 82, 157706). 183 R. S. Mahomed and B. C. Gardner, Ger. Offen. 2429254 (Chem. A h . , 1975, 82, 157771). 184 H. G. Braxton, M. E. Griffing, and J. G. Jolly, U.S.P. 3891449 (Chem. Abs., 1975, 83, 149055). 185 H. G. Braxton and A. Lehikoinen, U.S.P. 3891448 (Chem. Abs., 1975,83, 149054). W. B. Tuemmler, J. F. Start, and E. F. Orwoll, Ger. Offen. 2527589 (Chem. Abv., 1976, 84, 107038). l a 7 K. Nagai, H. Okada, I. Takeuchi, and K. Hara, Japan. Kokai 75 82041 (Chem. Abs., 1975,83, 207 144). 188 Y. Kametani and T. Nakahama, Japan. Kokai 75 82019 (Chem. Abs., 1975, 83, 207000). lB9 H. Maki, Japan. Kokai 75 39799 (Chem. Abs., 1975,83, 148477). 190 H. Maki, Japan. Kokai 75 67894 (Chem. Abs., 1975, 83, 207061). 191 H. Rose, H. Vollmer, J. Wortmann, and H. Jastrow, Ger. Offen. 2364337 (Chem. Abs., 1975, 83, 207059). 192 R. J. Clutter, U.S.P. 3865783 (Chem. Abs., 1975, 82, 157773). 1 9 3 H. Kawamura, T. Maikuma, and S. Ikeno, Japan. Kokai 74 33336 (Chem. Abs., 1975, 82, 157223). 194 G. W. McNeely, U.S.P. 3859249 (Chem. Abs., 1975,82, 141475). 170

230

Organophosphorus Chemistry

applications of this type, for p o l y a r n i d e ~ , ~cellulose-based ~~-~~~ fibres,lo8 epoxyresins,199and polyacetal resins.2ooAmino-,201-203 a l k ~ l - , ~and O ~ aryl-lg2> 204 cyclophosphazenes impart flame resistance. 8 Molecular Structures of PhosphazenesDetermined by X-Ray Diffraction Methods Compound

Comments

Plane containing C-N=P coplanar with triazene ring, P=N 1.622(5) A, C-N-P angle 121O Pph,]' [R~,,(co),H,]-' No data on P-N-P skeleton in preliminary publication Layer structure in crystal with extensive N -H * N hydrogen-bonding. Mean P-N(endo) 1.565 A, P-"(exo) 1.601 A Free base of hydrochloride where N,P,C&(NHPri), structure reported previously. Distorted (geminal) boat-shaped ring; protonation does not Naffect geometry of C12Py fragment \N=

[Ph3P=N-

195 196 197 198 199 200 201 202

203 2 04 205 206 207 208

209

Ref.

205

206 207

208

Earlier assignment corrected; irregular puckered ring, mean P -N(exo) 1.633 8,

209

Centrosymmetric, with phosphazene rings in slight boat conformation, with mean P-N 1.599(2) A, P-P 2.210(2) A

139

M. Fukuhara and S . Ozawa, Japan. Kokai 74 132398 (Chem. Abs., 1975, 82, 172556). M. Fukuhara, Japan. Kokai 75 142900 (Chem. Abs., 1976, 84, 107027). M, Fukuhara and S . Ozawa, Japan. Kokai 74 133470 (Chem. Abs., 1975, 83, 29808). K. Nagai, H. Okada, I. Takeuchi, and Y. Okutani, Japan. Kokai 75 139096 (Chem. Abs., 1976, 84, 61 116). V. Frank, E. W. Lard, and E. E. Stahly, U.S.P. 3867344 (Chem. Abs., 1975, 83, 29 151). V. A. Bykov, A. A. Volodin, G. I. Kurochkina, and L. M. Romanov, Russ. P. 455982 (Chem. Abs., 1975, 83, 60681). R. M. Murch and E. E. Stahly, U.S.P. 3933738 (Chem. Abs., 1976, 84, 136659). E. 0. Hook, G. R. Berbeco, and A. S. Obermayer, U.S.P. 3867186 (Chem. Abs., 1975, 82, 157 786). I. Masuda, T. Midorikawa, R. Kawamura, Y. Goto, and H. Kawano, Japan. Kokai 74 124323 (Chem. Abs., 1975, 82, 172465). M. Mizuno, K. Igi, and T. Akasawa, Japan. Kokai 75 48055 (Chem. Abs., 1975,83, 133205). T. S . Cameron, Kh. Mannan, M. Biddlestone, and R. A. Shaw, 2. Nuturforsch., 1975, 30b, 973. V. G. Albano, A. Ceriotti, P. Chini, G. Ciani, S. Martinengo, and W. M. Anker, J.C.S.Chem. Comm., 1975, 859. S . Pohl and B. Krebs, Chem. Ber., 1975, 108,2934. W. Polder and A. J. Wagner, Cryst. Struct. Comm., 1976, 5 , 253. T. T. Bamgboye, M. J. Begley, and D. B. Sowerby, J.C.S. Dalton, 1975, 2617.

Phosp hazenes Compound

210

211 212

23 1 Comments

Ref.

Bicyclic structure with mean phosphazene ring P-N 1.602(8) A. Pyramidal P-NEt-P nitrogen atom with P-N 1.772, 1.693 A

114

Centrosymmetric chair conformation with P-N 1.665(6) and 1.572(7) A

210

Centrosymmetric, with conformation like that of NsPs(0Me)ls. Mean P-N(endo) 1.548(9)A, one very large P-N-P angle 170.2’

21 1

Determined at - 140 “C. Ring has boat conformation with P=NP 1.574(4) A, P=NS 1.606(3) A

212

H. P. Calhoun, R. T. Oakley, N. L. Paddock, and J. Trotter, Canad. J . Chern., 1975,53,2413. H. P. Calhoun, N. L. Paddock, and J. Trotter, J.C.S. Dalton, 1976, 38. F. Van Bolhuis and J. C. Van de Grampel, Acta Cryst., 1976, B32, 1192.

11 Photochemical, Radical, and Deoxygenation Reactions BY R. S. DAVIDSON

1 Photochemical Reactions Further studies have been made of the quenching of excited singlet states by triphenylphosphine1*2and triphenyl phosphite.2 Rate constants were determined for the quenching of the fluorescence of a variety of 9-mono- and 9,lO-di-substituted anthracenes by the ph0sphine.l The constants approached the diffusion-controlled limit when electron-withdrawing substituents were present. The constants were markedly lower for anthracenes containing electron-donating substituents. It was proposed that high rate constants were obtained when quenching occurred by a predominantly electron-transfer process and that the lower rate constants reflected a change in the quenching mechanism to one in which an intermediate complex was formed where binding energy was mainly due to exciton resonance. However, it should be pointed out that the experimentally determined rate constants (k,) are composite rate constants i.e. ArH*(Sl)

k, k, + Ph3P + [ArHPh3P]* +ArH(S0) + PhsP(S0)

k-I

and lower than diffusion-controlled values are often obtained because of the increasing efficiency of the reverse process, i.e. inc~eases.~ Thus, before any real conclusions can be reached about the mechanism of the quenching process, the effect of temperature upon the quenching constants (k,) will have to be determined. Triphenylphosphine and triphenyl phosphite both quench the fluorescence of fluorenone (k, = 4.5 x logand 2.1 x lo81 mol-1 s-l in benzene solution).2 Since the quenching efficiency is insensitive to solvent polarity, it was concluded that the quenching complex had little charge-transfer character. The lower reactivity of the phosphite compared with phosphine and the lack of quenching by triphenylphosphine oxide demonstrated that the efficiencyof quenching was dependent on the availability of the lone pair on phosphorus. There has been the very interesting report that dialkyl(hydroxymethy1)phosphines rearrange to dialkylmethylphosphine oxides on irradiation with U.V. light.4 No mechanistic details are available. Irradiation of the phosphine (1) causes a molecular rearrangement, and it was proposed that the primary chemical reaction is C-P bond cleavage.6 a

5

M. E. R. Marcondes, V. G. Toscano, and R. G. Weiss, J. Amer. Chem. SOC.,1975, 97, 4485. R. H. Lema and J. C. Scaiano, Tetrahedron Letters, 1975, 4361. F. D. Lewis and C. E. Hoyle, J . Amer. Chem. SOC.,1975,97, 5950. B. Lippsmeier and K. Hestermann, Ger. Offen. 2 407460 (Chem. A h . , 1976, 84, 17557). W. Winter, Tetrahedron Letters, 1975, 3913.

232

Photochemical, Radical, and Deoxygenation Reactions

233

I

Ph

Irradiation of dianisyl alkyl phosphates gives alkyl phosphates and 4,4'-dimethoxybiphenyl in yields exceeding 90%.6 As stated by the authors, this type of reaction appears to have promise for the synthesis of nucleotides. The phosphonium compounds (2) normally give the phosphonates (3) quite readily on heating. However, when R = Ph the salts are thermally stable but will rearrange under the influence of U.V. radiation.'

Addition of tristearyl phosphite to polyethylene containing ferric acetylacetonate has been shown to decrease the stability of the polymer towards photo-oxidation.* 2 Phosphinidenes and Related Species A comprehensive review of the chemistry of phosphinidenes has been published,g and topics such as their preparation, spectroscopic properties, and reactions used to trap such species are dealt with. The chemistry of phosphinidene oxides and sulphides is also reviewed. Several reactions, e.g. of (4) (Scheme 1),lo (5),11 and (6),12 have been reported in which phosphinidene oxides are probably produced, although there is no conclusive evidence for the generation of such species. R. A. Finnegan and J. A. Matson, J.C.S. Chem. Comm., 1975, 928. C. Shin, Y. Yonezawa, Y. Sekine, and J. Yoshimura, Bull. Chem. SOC.Japan, 1975,48, 1321. * T. T. Sat0 and D. Hideo, Kobunshi Ronbunshu, 1975, 32, 598 (Chem. Abs., 1976, 84, 44898). U. Schmidt, Angew. Chem. Znternat. Edn., 1975, 14, 523. lo T.H.Chan and K. T. Nwe, Tetrahedron, 1975,31, 2537. l1 A. J. Fry and L.-I,. Chung, Tetrahedron Letters, 1976, 645. l2 C. J. R. Fookes and M. J. Gallagher, J.C.S. Perkin I , 1975, 1876.

Organophosphorus Chemistry

234

Reagents: i, Et3N; ii, R1C-CR2; iii, A.

R' Br

\i/ I

Rz

*

MeO-P=O

A

Scheme 1

MeO--Y-0

d

-

R'RZC=CR'R2

RL Br R2

+

MeOP=O

2Me OPH,

11

0 (6)

MeOP=O

+ H,P-0

+ MeO-+ BH

The reaction of cis- and trans-stilbene oxides with phenylphosphonothioic dichloride in the presence of magnesium gives cis- and trans-stilbene and (7).13 Phenylphosphinidene sulphide is postulated as being an intermediate. The zwitterion (8) bears a remarkable similarity to the controversial perepoxides which are thought to be intermediates in the reaction of singlet oxygen with alkenes.

3 Radical Reactions Several radical anions such as (9) have been prepared and their e.s.r. spectra recorded.'* It was found, from calculations, that dn-pn interactions are of much greater significance than pn-pn interactions. The previous report l5 that U.V. irradiation of phosphine in krypton gives PH, has been criticized.16The e.s.r. spectrum, previously interpreted as being due to PH, radicals, has been re-interpreted as being due to (H,PPH,)+= radicals. The calculated spectrum of this radical is in good agreement with the one obtained experimentally, and also there is a very close resemblance between this and the spectrum of radical (10). The phosphoranyl radical Me,PH has l3 l4

l5

S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, Bull. Chem. SOC.Japan, 1975, 48, 3733. A. G. Evans, J. C . Evans, and D . Sheppard, J.C.S. Perkin II, 1976, 492. C. A. McDowell, K. A. R. Mitchell, and P. Raghunathan, J . Chem. Phys., 1972, 57, 1699. T. A. Claxton, B. W. Fullam, E. Platt, and M. C. R. Symons, J.C.S. Dalton, 1975, 1395.

235

Photochemical, Radical, and Deoxygenation Reactions PhP(S) Cl,

+ Mg

+ Ph,,

- *XPh Ph

.H O-FPh

Ph,

(7) (Mixture of isomers)

.H

H WO+P h

I Ph (8)

M~,LPM~,

I I

s- sbeen prepared by y-irradiation of triinethylphosphine at - 196 O C . 1 7 The radical (Me,PPMe,)+* was also formed in this system. It was noted that the replacement of apical groups by groups less electronegative than RO in phosphoranyl radicals PX., leads to a transfer of spin density from the central atom to the o-orbitals, leading to a destabilization of the radical. Thus, as spin density in the apical bonds is increased, the tendency for phosphoranyl radicals to undergo an a-scission reaction is increased. There is good experimental evidence to support the view that a-scission occurs preferentially from apical positions.18 The kinetics of the a-scission reactions of R1R2P(OBut), have been examined by e.s.r. spectroscopy. In none of the cases examined could the reactivity of the radicals be explained solely on the ease of C-P bond fission, and therefore the conclusion was reached that it is the relative stabilities of the permutational isomers of the phosphoranyl radicals which are of prime importance. Thus in the case of (lla) and (llb), it is the less stable (lla) which undergoes the a-scission reaction. Just the opposite view has been put forwardxgto explain the reactivity of (12) towards the thiyl radicals (13a-c). From the fact that substitution is favoured over oxidation for the series (1 3c) > (13b) > (13a) it was concluded that the relative strengths of the C-P and C-S bonds controlled the outcome of these reactions. From a study of the products of the light-catalysed 17

1s 19

K. Nishikida and F. Williams, J. Amer. Chem. SOC.,1975, 97, 5462. J. W. Cooper and B. P. Roberts, J.C.S. Perkin II, 1976, 808. W. G. Bentrude and P. E. Rogers, J. Amer. Chem. SOC.,1976, 98, 1674.

236

OrganophosphorusChemistry

PhCH,P(OEt), +

(12)

_ . f

KP(OEt),

Oxidation

(13) a: R = Pri b: R = But c: R = 4-MeC,H4CCI, RSP(OEt), Substitution

II

S

addition of thiols to diphenylvinylphosphine(14) it appears that the addition of thiyl radicals to phosphines may well be reversible.20When R = Et, Prn, Bun, or Ph product (15) is exclusively obtained, whereas when R = But or PhCH2, (16) is the Ph,PeHCH,SR

Rp

Ph,KH=CH2 (14)

RSH

*

Ph,PCH,CH,R (15)

Ph,kH=CH,

I

SR

--+ Ph,PCH=CH,

II

sole product. Thermodynamic parameters for pseudorotation of several fluorinecontaining phosphoranyl radicals, e.g. EtOPF3and (EtO),PF,, have been obtained.21 y-Irradiation of trimethyl phosphite, trimethyl and tripropyl phosphorotrithioite, di-isopropylphosphinyl chloride, diphenylphosphinyl chloride, and diethylphosphorochloridodithioite has been shown to give radicals which appear to be derived uia phosphoranyl radicals generated by electron addition to the tervalent phosphorus compounds.22The reactions of these spectroscopically undetected phosphoranyl radicals are shown in Scheme 2. Other reactions observed included the formation of

R

R' + OPL,

II

X = OorS

S

Scheme 2

21 22

D. H. Brown, R. J. Cross, and D. Millington, Inorg. Nuclear Chem. Letters, 1975, 11, 7 8 3 ; J.C.S. Dalton, 1976, 334. I. H. Elson, M. J. Parrott, and B. P. Roberts, J.C.S. Chem. Comm., 1975, 586. B. W. Fullam and M. C. R. Symons, J.C.S. Dalton, 1975, 861.

237

Photochemical, Radical, and Deoxygenation Reactioris +.

species such as L,PPL, and L3P-PL3. The e.s.r. spectra of the radicals derived by photolysis of triethyl phosphite2, have been reinterpreted in the light of these results, and the radicals identified as (EtO),P and EtP(OEt),.,, The observed products of reactions can be easily interpreted as being produced via these radicals. It has been proposed that the radicals derived by y-irradiation of phosphites, phosphates, chlorophosphites, and chlorophosphates, and which have been detected by e.s.r spectroscopy, are radicals derived by an electron-capture reaction, e.g. formation of (17) and (18).24 ?-Irradiation of fluorophosphines in sulphur hexafluoride gives

Me'

+ (MeO),POH

Me'

f

d

o\P/H Me0

No

(MeO),PO

-

f

MeH

(1 7 )

MeH + MeOP(: 0)0(1 8)

fluorine-containing phosphoranyl radicals.26 When phosphorus pentahalides are y-irradiated, phosphoranyl radicals are obtained in addition to -*PCls and 2-'Pc16 radicals.26y-Irradiation of phosphorus oxyhalides2 7 and alkyl and aryl phosphorodichloridates28 at 77 K gives phosphoranyl radicals by an electron-attachment reaction. When polar solvents are used the phosphoranyl radicals can break up either by loss of halide ion or by formation of phosphino radicals.28The radicals obtained by y-irradiation of phenylphosphinic and phenylphosphonic acids have been examined by e.s.r. At room temperature, phenylphosphinic acid gave PhP( :O)OH and cyclohexadienyl radicals having the partial structures (19) and (20). In contrast, irradiation at 77 K gave radical (21). Annealing of the matrix led to the observation of radicals (22). The proton in this radical was shown by

deuterium labelling to have been originally bound to phosphorus. Cyclohexadienyl radicals of the type (19) and (20) were also obtained from phenylphosphonic acid and diphenylphosphinic acid. Attempts have been made to demonstrate that the formation of radicals such as (24) involves prior formation of phosphoranyl radicals such 23 24

25 26 27 28 29

K. Terauchi and H. Sakurai, Bull. Chem. SOC.Japan, 1969, 41, 1736. C. M. L. Kerr, K. Webster, and F. Williams, J. Phys. Chem., 1975, 79, 2650, 2663. A. J. Colussi, J. R. Morton, and K. F. Preston, J. Phys. Chem., 1975, 79, 1855. S. P. Mishra and M. C. R. Symons, J.C.S. Dalton, 1976, 139. A. R. Boate, J. R. Morton, and K. F. Preston, J . Phys. Chem., 1976, 80, 409. D. J. Nelson and M. C. R. Symons, J.C.S. Dalton, 1975, 1164. S. P. Mishra and M. C. R. Symons, J.C.S. Perkin ZI, 1976, 21.

Organophosphorus Chemistry

238

as (23).30Examination of the radicals produced by y-irradiation of dimethyl phenylphosphonous acid in a propan-2-01 matrix gave indications that the sequence (23)+(24) does operate. Radical (25) was also detected. Radicals having a similar

RO + PhP(OMe),

--+--P

OR ,OMe

I

I

\.4r OMe

-

I_f

+ , O R

&-P-OMe ‘ 0 hfe

OMe OMe

structure have been produced by electrochemical oxidation of phosphines in solution31 Well-resolved e.s.r. spectra were obtained. By the use of open-shell CNDO$ calculations, the geometries of a variety of phosphoranyl radicals have been determined.32The validity of using this type of calculation is attested to by the fact that the calculated hyperfine coupling constants for the radicals are in close agreement with the experimentally determined ones. The anion of di-isopropyl phosphorothiolothionic acid (26) reduces hydroxyl radicals, and the radical (27) so produced is detectable by e . ~ . rAttempts .~~ to observe these radicals by photolysis of the free acid were unsuccessful. However, the use of a spin trap (e.g. N-methylene-t-butylamineN-oxide) enabled radicals in this system and other closely related systems [e.g.with (28)] to be observed by e.s.r. spectroscopy.

Photolysis of peroxydisulphate anions in aqueous solution produces the SO,-= sulphate radical. This radical reacts with phosphoric acid and its anions to generate phosphorus-containing radicals which can be trapped by such compounds as fumaric 30

31 32 33 34

M. C. R. Symons, Mol. Phys., 1975, 30, 1921. W. B. Gara and B. P. Roberts, J.C.S. Chem. Comm., 1975, 949. J. M. F. van Dijk, J. F. M. Perrings, and H. M. Buck, J. Amer. Chem. SOC., 1975, 97, 4836. 6. Brunton, B. C. Gilbert, and R. J. Mawby, J.C.S. Perkin I I , 1976, 650. 0. P. Chawla and R. W. Fessenden, J. Phys. Chem., 1975,79, 2693.

239

Photochemical, Radical, and Deoxygenation Reactions

Electron attachment to dinucleoside phosphates leads to the formation of radical ions in which the electron has added to the more easily reduced heterocyclic base.35 Several examples have been reported of the formation of phosphorus-containing persistent radicals, e.g. (29) and (30).36Addition of a variety of radicals to 2,4,6-tri-tbutylphosphorin produces persistent radicals of the type (31). The e.s.r. spectrum of (32) indicates that its preferred conformation is the one in which the half-filled

,But

+ Se-c 'But

(EtO),E;=o

---+

B u y 8 Bu'/,-Se

II

,P(OEt),

(32)

p-orbital eclipses the Se-P bond.37Phosphorins such as (33) react with diazonium salts in methanol to give products (34) and (35).38

bBUt ArN,X

MeOH

*

qAr

But

(3.3)

Several very stable radicals (e.g.those derived from AIBN) react with tetraphenylbiphosphine in a homolytic displacement reaction.39Phosphoranyl radicals, e.g. (36), were postulated as being intermediates. The reaction of the triplet state of olefin (37) is thought to occur via a similar mechanism. In the presence of cuprous chloride, trichloromethylphosphonic dichloride (38) adds to a variety of alkenes and dienes via a free-radical process.4oThere have been 35

36 37 38 4o

M. D. Sevilla, R. Failor, C. Clark, R. A. Holroyd, and M. Pettei, J. Phys. Chem., 1976,80,353. D. Griller, K. Dimroth, T. M. Fyles, and K. U. Ingold, J. Amer. Chem. SOC.,1975, 97, 5526. J. C. Scaiano and K. U. Ingold, J.C.S. Chem. Comm., 1976,205. 0 . Schaffer and K. Dimroth, Chem. Ber., 1975, 108, 3281. R. Okazaki, Y.Hirabayashi, K. Tamura, and N. Inamoto, J.C.S. Perkin I , 1976, 1034. H. Rosin and H. Asscher, J. Org. Chem., 1975, 40, 3298.

240

Organophosphorus Chemistry Ph,PPPh,

A

-t

Me,C-N-N-CMe,

Ph,iPPh,

l

Ph,PCMe, + Ph,P

Me,CCO,Me

I

I

C0,Me

---+

C0,Me

(36)

C0,Me

Ph,C=CH2m

Ph,P-PPh,

Ph,PPI’h,

cuc1,

CUCl

+ CI,CPOCl, (38)

-

+ Cl,CPOCI,

MeCHCH,

*

c1 MeCHCH,L--PCI,

I ll

c1 0

I

CUQ, %

MeCHCH2C-PC1,

I

c1

I II

Cl 0

further investigations of the reaction of phosphorus trichloride with toluene in the presence of oxygen in an attempt to find a satisfactory mechanism to account for the formation of 4-methylphenylphenylmethane.41Other studies include the hydrogenand the electrochemical reduction of abstraction reactions of recoil 32P phosphacyanine dyes.43

4 Deoxygenation and Desulphurization Reactions A review has been published which describes the use of deoxygenation reactions in synthesis.44There have been some interesting uses of the deoxygenation of 1,4endoperoxides, prepared by the addition of singlet oxygen to cyclohexa-l,4-dienes. Epoxide (39)45and the benzene diepoxide (40)4shave been synthesized in this way. Pyrazine (41) reacts with singlet oxygen to give a 1,4-endoperoxide which is reduced by triphenylphosphine to (42).47 The chemistry of arene oxides is of particular interest because of the possible role of these compounds in chemical carcinogenesis. Deoxygenation reactions have been successfully used in the synthesis of these compounds, e.g. (43),4* (44),49 and (45).50 Another application of deoxygenation reactions has been to the polemical problem as to the mechanism of ozonolysis of olefins. An ozonide was allowed to react61awith acetaldehyde labelled at oxygen to give a molozonide, which was deoxygenated by triphenylphosphine. Examination of the products showed that the label was located at the ether oxygen, which once again makes the refined Criegee mechanism51bthe favourite. There is a valuable discussion 41 42 43

44 45 46

*7 48

49

50

51

Y. Okamoto and H. Sakurai, Bull. Chem. SOC.Japan, 1975, 48, 3407. 0. F. Zeck, G. P. Gennaro, and Y.-N. Tang, J . Amer. Cliem. SOC.,1975, 97, 4498. H. Oehling, F. Baer, and K. Dimroth, Tetrahedron Letters, 1976, 1329. T. Mukaiyama, Angew. Chem. Internat. Edn., 1976, 15, 94. M. Oda, M. Oda, and Y. Kitahara, Tetrahedron Letters, 1976, 839. C. H. Foster and G . A. Berchtold, J . Org. Chem., 1975, 40, 3743. J. L. Markham and P. G . Sammes, J.C.S. Chem. Comm., 1976,417. G. W. Griffin, S. K. Satra, N. E. Brightwell, K. Ishikawa, andN. S. Bhacca, Tetrahedron Letters, 1976, 1239. R. M. Moriarty, P. Dansette, and D. M. Jerina, Tetrahedron Letters, 1975, 2557. S. C. Agarwal and B. L. Van Duuren, J . Org. Chem., 1975, 40,2307. (a) K . L. Gallaher and R. L. Kuczkowski, J. Org. Chem., 1976, 41, 892; (b) N. L. Bauld, J. A. Thompson, C. E. Hudson, and P. S. Bailey, J . Anzer. Clzem. SOC.,1968, 90, 1822.

Photochemical, Radical, and Deoxygenation Reactions

241

Ph,P

(Me,N),P

CHO

of the use of labelling techniques in examining the chemistry of ozonides. The ozonide of triphenyl phosphite has found use in the synthesis of alkenes via the oxidation of ylides.62 52

H. J. Bestmann, L. Kisielowski, and W.Distler, Artgew. Chern. Internat. Edn., 1976, 15, 298.

242

Organophosphorus Chemistry

The deoxygenation of some penicillin and cephalosporin sulphoxides has been accomplished by the use of phosphorus p e n t a ~ u l p h i d e .The ~ ~ ~reactive species responsible for deoxygenation was not identified. A particularly mild method for reducing sulphoxides to sulphides involves the reaction of the sulphoxide with 2-chloro-l,3,2-benzodioxaphosphole at room f e m p e r a t ~ r e . ~ Yields ~ in excess of 80 % were reported. Acyl-nitroso-compounds are deoxygenated by triphenylphosphine to give isocyanates, and reaction via the zwitterion (46) was po~tulated.~*

The reaction of several derivatives of N-nitrosoanilines with tervalent phosphorus compounds has been shown to give diazo-benzenes, which in some cases give benzynes in low yield.55A kinetic study has been made of the deoxygenation of 2-nitrobenzylidenederivatives of substituted anilines by several tervalent phosphorus esters and a m i d e ~The . ~ ~reaction is very sensitive to the nature of the deoxygenating agent, and the order of reactivity observed was (Me,N),P > (EtO),PMe z EtOPPh, > EtOP(NEt 2)2 z (Et0)2PNC5Hlo> (MeO)3Pz(EtO),P z (PriO)3P. Tervalent phosphorus compounds having the phosphorus atom contained in a five-membered ring are relatively unreactive. This is attributed to the fact that ring strain in the tetragonal intermediate produced by attack upon the nitro-group is much greater than in the starting phosphorus compound. There has been a series of papers on the deoxygenation of 2-nitrophenyl phenyl ethers and sulphides. Of particular interest has been the role of pentacovalent intermediates (47) in these reactions. These are certainly not the primary intermediates in the reactions but are of great importance in determining the course of the reaction. Their genesis is thought to be that shown in Scheme 3.57 A number of pentacovalent compounds of the type (47) have been isolated from reactions of ether^.^'-^^ The structures of the compounds were established by n.m.r. spectroscopy and X-ray ~rystallography.~~~ 5 9 The stability of these intermediates 53 54

55 S6

57

59

59

(a)R. G . Micetich, Tetrahedron Letters, 1976,971 ;(b) D. W. Chasar and T. M. Pratt, Synthesis, 1976,262. J. E. T. Corrie, G . W. Kirby, and R. P. Sharma, J.C.S. Chem. Comm., 1975, 915. J. I. G . Cadogan, A. G. Rowley, J. T. Sharp, B. Sledzinski, and N. H. Wilson, J.C.S. Perkin I , 1975, 1072. M.-A. Armour, J. I. G . Cadogan, and D. S. B. Grace, J.C.S. Perkin l I , 1975, 1185. J. I. G . Cadogan, D. S. B. Grace, P. K. K. Lim, and B. S. Tait, J.C.S. Perkin I , 1975, 2376. J. I. G . Cadogan, D. S. B. Grace, and B. S. Tait, J.C.S. Perkin I , 1975, 2386. J. I. G . Cadogan, R. 0. Gould, S. E. B. Gould, P. A. Sadler, S. J. Swire, and B. S. Tait, J.C.S. Perlcin I , 1975, 2392.

Photochemical, Radical, and Deoxygenation Reactions - Nitrene

-

Zwitterionic products

X = OorS

243

-+ I.

0

Z

Q

R

3

R'

i

(47)

Scheme 3

accounts for the fact that these reactions failed to give phenoxazenes. The intermediates are photochemically labile, and carbazoles, e.g. (48), have been successfully synthesized by employing this reaction.so Deoxygenation of 2-nitrophenyl phenyl sulphides gives phosphoramidates (49) via

(47)

X T S R' = R2 = Me R3 = OH

R4 = Et Rs = OKt

7

+ a t N-P(OEt),

MeoMe I

OH

(49) J. I. G. Cadogan, B. S. Tait, and N. J. Tweddle, J.C.S. Chem. Comm., 1975, 847.

244

Organophosphorus Cheniistry

intermediates such as (47).61a2 * When the ortho-positions in the ring attacked by the intermediate derived from the nitro-group are free, phenothiazines are produced. Normally the thiazaphosphoranes (47; X = S) rearrange so rapidly that they cannot be isolated."lb However, their intermediacy can be detected by 31Pn.m.r. spectroscopy.61uFurthermore, if the tervalent phosphorus reagent has its phosphorus atom contained in a five-membered ring, stable thiazaphosphoranes can be isolated.61aTheir structures have been verified by X-ray crystallography. Once again, the deoxygenation of nitro-compounds has found use in the synthesis of heterocyclic c o r n p ~ u n d s . ~Several ~ - ~ ~ 2-nitrophenyl-substitutedindoles, e.g. (50) and (51), are deoxygenated on reaction with triethyl phosphite.62The reaction of H

+

\

Me

S-chloro-phosphinothiolateswith phosphorus trichloride leads to desulphurization.65 The reaction of sulphenates with phosphines leads to deoxygenation,66and not (as previously reported) to desulphurization. Even when the ion pair (52; R1 = R2 = Me, RS = Bun) was generated from the sulphide (53), the reaction still led to R'SOR' + R3P --+ R10-PR3,

I SR2

+ I

R'SR2 +

R10$R33 t

SR2

R10$R3,

I

SR2 (52)

R' OR2

+

R3,B (5 3)

61 62

63

65 G6

(a) J. I. G . Cadogan, R. 0. Gould, and N. J. Tweddle, J.C.S. Chem. Comm., 1975, 773; (b) J. I. G. Cadogan and B. S. Tait, J.C.S. Perkin I , 1975, 2396. A. H. Jackson, D. N. Johnston, and P. V. R. Shannon, J.C.S. Chem. Comm., 1975, 911. I. M. McRobbie, 0. Meth-Cohn, and H. Suscliitzky, Tetrahedron Letters, 1976, 925. T. Kametani, Y. Fujimoto, and M. Mizushima, Heterocycles, 1975, 3, 619. J. Omelanczuk, P. Kielbasinski, J. Michalski, J. Mikolajczak, M. Mikolajczyk, and A. Skowronska, Tetrahedron, 1975, 31, 2809. D. H. R. Barton, D. P. Manly, and D. A. Widdowson, J.C.S. Perkin I , 1975, 1568.

245

Photochemical, Radical, and Deoxygenation Reactions

deoxygenation. By means of suitable labelling, it was shown that the disulphides (54) and (55) are desulphurized by triphenylphosphine by different me~hanisms.~? Presumably the ion pair (56b) can collapse to give the phosphine sulphide more readily than can (56a) because of the steric effect of the diphenylmethyl group. PhCH2SS*Ac

Ph3P F

PhCH,S*Ac + Ph,PS

S* = %

(54)

P&CHSS*Ac

W3P

: ph,PS*

+ PhCHSAc

(55)

Ph$HS$Ph, 'SAC (56d

AcSSPh, kHPh,

(56b)

Further use has been made of the reaction of disulphides with tervalent phosphorus compounds in phosphorylation reactions, e.g. in the synthesis of (57).68 S

II

+ Ph,P

0

+ ROCSPPh,

SCOR

II

S

OH

Desulphurization of compounds such as (58) has again attracted attention.6QIn the case of (58), complete desulphurization gives (60), and the reaction was shown by trapping experiments to occur via the zwitterion (59). The desulphurization of disulphides by tervalent phosphorus compounds has been the subject of a review.'O The light-induced desulphurization of benzylic sulphides by phosphites has found further use in the synthesis of cyclophanes which exhibit the formation of intramolecular charge-transfer complexes, e.g. (61) and (62).71 67 68

6Q 70

S. Kawamura, A. Sato, T. Nakabayashi, and M. Hamada, Chem. Letters, 1975, 1231. H. Takaku, M. Yamana, and Y. Enoki, J. Org. Chem., 1976,41, 1261. T. Sat0 and T. Hino, Tetrahedron, 1976, 32, 507. E. J. Griffith and M. Grayson, 'Topics in Phosphorus Chemistry', J. Wiley, New York, 1975, Vol. 8. H. Tatemitsu, T. Otsubo, Y. Sakata, and S. Misumi, Tetrahedron Letters, 1975, 3059.

9

246

Organophosphorus Chemistry

/

.1

EtOCH=CII,

(59)

(63) X = 0 , S, or Se

Another synthesis of olefins has been described in which the desulphurization of thiirans by triphenylphosphine is featured.72There have been many reports of the synthesis of compounds of the type (63). These form charge-transfer complexes with acceptors such as tetracyanoquinodimethane which have metallic properties. The

72

A. 1. Meyers and M. E. Ford, Tetrahedron Letters, 1975, 2861.

Photochemical, Radical, and Deoxygenation Reactions

247

desulphurization of (64), which yields (63; X = 0, R = CN), has been the subject of an intensive ~tudy.7~ Compounds (65) and (66) are proposed intermediates whereas (67) and (68) are compounds which have been isolated from the reaction mixture. 5 Deselenation Reactions The three papers in this section are all concerned with the preparation of compounds such as (63). Compounds (69),74(70a),74(70b),75and (71) 76 were usually converted

(70) a: X = S ; Y = CH, b: X = Se; Y = S

MeSe

(Me01, P f

(63; X = Se, R = MeSe)

MeSe (71)

into derivatives of (63) in quite high yields by reaction with phosphites. Synthesis of these compounds by desulphurization of the correspondingthiocarbonyl compounds often afforded disappointingly low yields of the olefins (63).74

73 74

M. G. Miles, J. S. Wager, J. D. Wilson, and A. R. Siedle, J. Org. Chem., 1975, 40, 2577. H. K. Spencer, M. V. Lakshmikantham, M. P. Cava, and A. F. Garito, J.C.S. Chem. Comm., 1975, 867.

75

76

C. Berg, K. Bechgaard, J. R. Andersen, and C. S. Jacobsen, Tetrahedron Letters, 1976, 1719. E. M. Engler, D. C. Green, and J. Q. Chambers, J.C.S.Chem. Comm.,1976, 148.

I2 Physical Methods BY J. C. TEBBY

The abbreviations PIII, PIV, and PV refer to the co-ordination number of phosphorus and the compounds in each subsection are usually dealt with in this order. A number of relevant theoretical and inorganic studies are included in this chapter. In the formulae the letter R represents hydrogen, alkyl, or aryl, X represents electronegative substituents, Ch represents the chalcogenides (usually oxygen and sulphur), and Y and Z are used to indicate a wide variety of substituents. 1 Nuclear Magnetic Resonance Spectroscopy The very high accuracy which may be obtained by the pulsed Fourier transform method has been demonstrated using o-phenylene phosphorochloridite.l Biological Applications.-Following the extensive n.m.r. studies of the stereochemistry of nucleotides2attention is now being turned to linking the n.m.r. results with circular dichroismS, and other proper tie^.^ Phosphorus n.m.r. spectroscopy has been used to assist oligonucleotide synthesis6and has been applied to model and biological membrane systems.*Procedures have been described for the measurement of an order parameter for the phosphate head group in phospholipid bilayen6 Structural and dynamical studies of mixed chlorophyll-phosphatidylcholinebilayers have been reported. Phosphonium phosphatidylcholine has been prepared from phosphonium choline (1) in which the nitrogen atom of choline is replaced by a

phosphorus atom. It gives a unique and sharp phosphorus-31 signal which is distinct from the phosphate resonances and also sensitive to shift reagents.8There appears to be minimal perturbation of the membranes9 and the derivatives exhibit similar 1 2

3 4

5 6

7 8 Q

L. Ernst and D. N. Lincoln, J. Mugn. Resonance, 1974, 16, 190. C. R. Lee, Diss. Abs. Internnt. ( B ) , 1976, 36, 3928; R. H. Sarma and R. J. Mynott, Jerusalem Symp. Quantum Chem. Biochem., 1973, 5, 591. G. Reitz and W. Pfleiderer, Chem. Ber., 1975, 108, 2895. A. V. Azhaev, A. A. Kraevskii, and V. L. Florent’ev, Nucleic Acids Res., 1975,2, 1433. D. G. Knorre, A. S. Levina, and T. N. Shubina, Izuest. sibirsk. Otdel. Akad. Nuuk, Ser. khim. Nauk, 1975, 118. A. C. McLaughlin, P. R. Cullis, M. A. Hemming, D. I. Hoult, G. K. Radda, G. Ritchie, P. J. Seeley, and R. E. Richaras, F.E.B.S. Letters, 1975, 57, 213. F. Podo, J. E. Cain, and J. K. Blasie, Biochim. Biophys. Actu, 1976, 419, 19. E. Sim, P. R. Cullis, and R. E. Richards, Biochem. J., 1975,151, 555. E. Sim and A. Pasternak, Biochem. J., 1976, 154, 105.

248

Physical Methods

249

temperature-dependent spectra to phosphatidylcholine.* Studies of 5’-guanosine monophosphate,1° tubercidin 5’-phosphate,11 and the hydration of phosphatidylethanolamine12have also appeared. Use of very high magnetic fields, which may be obtained from super-conducting magnets, permits the chemical shielding anisotropy to dominate dipolar broadening. In this way, order parameters have been estimated for lipid phosphates.13 Proton decoupling has been used to remove PH dipolar broadening so as to reveal the tensorial information contained in the chemical shielding anisotropy of rigid or slowly moving phospholipid molecules.14In addition the principal values and orientation of the shielding tensor were determined from the 31Pspectrum of a single crystal of phosphorylethanolamine.The broader 31P signals of t-RNA at high field (65 kG) are attributed to chemical shift anisotropy.16 The 31Pn.m.r. spectra of developing tadpoles showed that the main phosphorus component was yolk phosphoprotein.ls Inorganic phosphate (ca. 30 mmol/embryo) was detected at the swimming tadpole stage. It appeared that the phosphate groups of the nucleotide triphosphates were bound in uiuo to a divalent cation. The middle phosphate groups of polyphosphates have been detected in the 145.7 MHz 31P spectra of intact yeast ce1ls.l’ A preliminary report of high-resolution 31P n.m.r. spectroscopy of normal and malignant tissues discusses the possible use of n.m.r. in cancer therapy.ls Phosphorus n.m.r. has also been used to determine the pKa values of myo-inositol hexaph~sphatel~ and the interactions of phosphates with haemoglobin.2o Chemical Shifts and Shielding Effects.-Phosphorus-3I. The positive shifts ( 8 ~ ) which are reported in this chapter are upfield from 85 % phosphoric acid. 8p of PI Compounds. Methylidynephosphine (2) has dp +32.0 p.p.m.,21 which is approximately 35 p.p.m. upfield of protonated derivatives of this compound.22a Thus the chemical shifts are similar to ordinary phosphines and their salts.

10 11

la 18 14

15 16 17

T. J. Pinnavaia, H. Miles, and E. D. Becker, J. Amer. Chem. Soc., 1975,97,7198. F. E. Evans and R. H. Sarma, Cancer Res., 1975,35, 1458. R. P. Taylor, Arch. Biochem. Biophys., 1976,173, 596. B. De Kruyff, P. R. Cullis, G. K. Radda, and R. E. Richards, Biochim. Biophys. Actu, 1976, 419,411; P. R. Cullis, B. De Kruyff, and R. E. Richards, ibid., 1976,426, 433. S. J. Kohler and M. P. Klein, Biochemistry, 1976, 15, 967. M. Gueron and R. G. Shulman, Proc. Nat. Acad. Sci. U.S.A., 1975,72, 3482. A. Colman and D. G . Gadian, European J. Biochem., 1976,61, 387.

J. M. Salhany, T. Yamane, R. G. Shulman, and S. Ogawa, Proc. Nut. Acad. Sci. U.S.A., 1975, 72, 4966.

l8 19 20

21

K. Zaner and R. Damadian, Physiol. Chem. Phys., 1975, 7 , 437. A. J. R. Costello, T. Glonek, and T. C. Myers, Carbohydrate Res., 1976, 46, 159. C. Ho, Ann. New York Acad. Sci., 1974,241 ;A. J. R. Costello, W. E. Marshall, A. Omachi, and T. 0. Henderson, Biochim. Biophys. Acta, 1976,427, 481. S. P. Anderson, H. Goldwhite, D. KO,A. Letsou, and F. Esparza, J.C.S. Chem. Comm., 1975,

744. 22

‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, (a) 1975, Vol. 7 , Chap. 12; (b) 1970, Vol. 1, Chap. 11; (c) 1973, Vol. 5, Chap. 11.

250

Organophosphorus Chemistry

8~ ofPII1 Compounds. The chemical shifts of the phospholans (3) allow the estimation of the relative configurations in these The cis-2,3-diphenylphospholans, e.g. (3; R = Ph, X = 0),resonate at lower field than the trans-isomers. For other substituents the reverse generally applies. The stereochemistry of the dioxaphosphorinans (4), which has been rationalized in terms of lone-pair interaction^,^^ also manifests itself in stereo-dependent chemical shifts.26The strong dependence of 8~ on the steric disposition of the phosphorus groups on a cyclohexane ring has enabled the determination of conformational free-energy differences between (5) and (6).2s The Me I

PH, and PMe, groups follow the trend for methyl groups, with the axial group appearing more upfield. The opposite is true for the PCI, and four-co-ordinate groups. The reversal of the effect for the PCl, group is most striking (ASP 14.3 p.p.m.), showing that steric compression does not always produce shielding. By lowering the temperature, the individual conformers were observed directly, and AG * values calculated from Tc were in good agreement with those calculated from the averaged chemical shifts. It was evident that replacement of the 4-methyl group by the t-butyl group had only a small effect on 6~ of the equatorial phosphorus groups. The disappearance of the 31Psignal for (5 and 6; R = Me) near Tc occurred as a consequence of the very large difference in 8~ (axial) and 8~ (equatorial). 6~ of PIv Compounds. The reactions of alkyl-lithium reagents with methylphosphonium salts give lithium salt adducts (7) and not pure methylenephosphoranes (8). This accounts for the similarity of the chemical shifts of ylides and corresponding salts which has been observed in several cases. Other salts such as the ethyl and isopropyl compounds give the ylides if the solution of salt and organolithium reagent is stirred for at least 2 h. CND0/2 Calculations indicate that the lithium ion does not significantly alter the electron density or conformation about the methylene group except that the phosphorus atom loses electron density.27The subject of d-orbital

26

A. Zschunke, H. Meyer, and K. Issleib, Org. Magn. Resonance, 1975, 7 , 470. R. F. Hudson and J. G. Verkade, Tetrahedron Letters, 1975, 3231. T. J. Bartczak, A. Christensen, R. Kinas, and W. J. Stec, Tetrahedron Letters, 1975, 37, 3243. M. D. Gordon and L. D. Quin, J. Amer. Chem. SOC.,1976,98,15; J.C.S. Chem. Comm., 1975,

27

T. A. Albright and E. E. Schweizer, J. Org. Chem., 1976, 41, 1168.

23 24 25

35.

Physical Methods

25 1

participation continues to attract much attention.28SCF MO calculations on ylides show that coulombic attraction can account, on its own, for the short C-P bond.29 The trimethylfluorophosphonium ion (9; R = Me) resonates well downfield ( 8 ~ - 142.7 p.p.m.) of the triphenyl analogue (9; R = Ph; 8~ -93.7 ~.p.m.).~O This follows the trend of quaternary salts and phosphine oxides. The pronounced 10 p.p.m. upfield shift upon replacing the ,!?-methylgroup of the phospholen (10; Y = Me; BP -76.0 p.p.m.) by a ,&rnethoxy-group is attributed to a resonance interaction by the methoxy-group in (10; Y = MeO) with the phosphorus atom through the double bond.31The resultant increase in dn-p,, bonding could replace the loss of dn--pnbonding which is thought to be the cause of the downfield shift for cyclic phosphine oxides compared to acyclic oxides. The deviation from a plot of YP-o against 8p for the ethyl esters (11) when the group Y is ethoxy, diethylamino, and acetyl has also been attributed to dn-p, c ~ n j u g a t i o nIn . ~error, ~ it was reported in the previous volume22a that some mixed chalcogenide anhydrides showed unusual shielding. The shifts were downfield, as is usual for mixed ligands and shown also by the thio-esters (12) and the corresponding alkylated derivatives (1 3).33 In the latter work the shifts were rationalized in terms of the electronegativitiesof the ligands. The methyl thiophosphonates (14) have also been The position of the selenide 0

0

II

YP(OEt),

S

I1

(EtO),-,PEt

SEt

I

(EtO), -.P'Et X-

I(/SR MeP, OR

atom in the selenopyrophosphates has a large influence on BP. Thus the symmetrical pyrophosphate (15) has d~ -0.6 whereas for (16) 8p(se) is -43.6 ~ . p . m The . ~ ~cisgeometry of the phosphorocyanates (17) causes the phosphorus atom to resonate 4-5 p.p.m. upfield of the trans-isomer for both the oxides and the ~ e l e n i d e sThe .~~ nitrile group exhibits its usual shielding effect in all the isomers.

28

W. I. Shiau, Diss. Abs. Internat. ( B ) , 1975,36,2817; N. Inamoto, Kagaku No Ryoiki, 1975,29, 254; R. I. Yurchenko, 0. M. Voitsekhovskaya, and I. N. Zhmurova, J. Gen. Chem. (U.S.S.R.),

29

M.-H. Whangbo, S. Wolfe, and F. Bernardi, Canad. J. Chem., 1975, 53, 3040. F. See1 and H. J. Bassler, 2. anorg. Chem., 1975, 418, 263. S. G. Borleske and L. D. Quin, Phosphorus, 1975, 5, 173. V. E. Bel'skii, R. F. Bakeeva, L. A. Kudryavtseva, A. M. Karguzova, and B. E. vanov, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1511. R. Radeglia, J. Schulze, and H. Teichmann, Z . Chem., 1975, 15, 357. A. A. Abduvakhabov, A. A. Sadykov, Kh. A. Aslanov, N. N. Godovikov, and A S. Sadykov, Doklady Akad. Nauk Uzbek. S.S.R., 1974,31, 30. D. S. Rycroft and R. F. M. White, J.C.S. Chem. Comm., 1974, 444. B. Uznanski and W. J. Stec, Synthesis, 1975, 11, 735.

1975,45, 1927. 30 31 32 33 34

35

36

252

Organophosphorus Chemistry

6~ of Pv and PVI Compounds. The chemical shifts of a number of derivatives of the

monocyclic oxyphosphorane (18) have been rec~rded.~' The chemical shifts of the spirophosphoranes (19) varied little (43.7 to 45.0p.p.m.) as R was varied from methyl through a series of aryl substituent~.~~ The resonances at - 19 p.p.m. which appear when DMF or pyridine are mixed with phenylphosphonyl dichloride have been attributed to the complexes (20);39resonances at + 1 and - 1 p.p.m. were assigned to the dissociated molecules. Five-co-ordinate Arbuzov intermediates (21 ;

= OEt) have been detected in the reactions of halogen with a cyclic p h o ~ p h i t e ; ~ ~ the reaction with chlorine gave a resonance at 6~ + 35 and bromine gave a resonance at BP 195 p.p.m. The latter is at higher field than the tribromo-compound (21 ; X = Y = Br; 6~ 189 p.p.m.) and the chlorodibromo-compound (21 ;X = Br, Y = C1; BP 131 p.p.m.). Formation of six-co-ordinate compounds from spirooxyphosphoranes has been reported.41The chemical shifts are to high field of the corresponding oxyphosphoranes. Carbon-13. Steric compression by axial P substituents produces a 'so-called' y-effect by their interaction with the two axial protons on the same side of the ring, and there is a resultant upfield shift of the carbon atoms bearing the axial protons. This effect has been noted for a number of dioxaphosphorinans (22)42143 as well as for phosphorinans.22aA small but significant shift of the C-4 resonance occurs when the

Y

+

+

+

OH (24) phosphorinanone (23) is converted into its PIv derivative^.^^ The effect is observed for the phosphorinanols and phosphorinans, and it is therefore independent of both the hybridization of the C-4 atom and the presence of substituents at C-4. It is also 37

38

39 40

41

42 43

44

C. Malavaud and J. Barrans, Tetrahedron Letters, 1975, 3077. D. Houalla, T. Mouheigh, M. Sanchez, and R. Wolf, Phosphorus, 1975,5, 229. W. R. Purdum, K. D. Berlin, S. J. Kelly, and L. G. Butler, J. Org. Chem., 1976, 41, 1160. A. Skowronska, J. Mikolajczak, and J. Michalski, J.C.S. Chem. Comm., 1975, 791. A. Munoz, G. Gence, M. Koenig, and R. Wolf, Bull. SOC.chim. France, 1975,909; A. Munoz, G. Gence, M. Koenig, and R. Wolf, Compt. rend., 1975,280, C, 485; A. Munoz, M. Sanchez, M. Koenig, and R. Wolf, Bull. SOC.chim. France, 1974, 2193. W. J. Stec and A. Okruszek, J.C.S. Perkin I, 1975, 1828. W. G. Bentrude and H. W. Tan,J. Amer. Chem. SOC.,1972,94,8222; 1973,95,4666. J. J. Breen, S. 0. Lee, and L. D. Quin, J. Org. Chem., 1975,40,2245.

Physical Methods

253

independent of the size of the phosphorus substituent and the position of the conformational equilibrium. The 13Cn.m.r. spectrum of the P I V derivatives of (23) in aqueous solutions indicated that the ketone is in equilibrium with substantial amounts of the diol. In fact, solutions of the oxides at 10 "C were completely in the diol form (24). Several bicyclic phosphorinans such as (25) have been prepared.46 When the P-substituent is an axial phenyl group, as in (25), the y-effect, discussed above, is cancelled and there is a net deshielding effect of the starred carbon atoms. The shielding of the C-1 atom of the vinylphosphonium salts (26) increased with Ph

I

H

Y

PO(OMe),

increased electron-donor power of Y .46 The correspondingslight but definite decrease in the shielding of the C-1 phenyl carbons together with changes in coupling constants supported increased dn-pn conjugation. The chemical shift of the C-1 atom of the phosphonium ylide (8; R = Ph) ( 6 0.4p.p.m.) ~ is at higher field than that previously reported, which was the chemical shift of the lithium adduct (7; R = Ph).27The stereochemical dependence of 6c in phosphonates has been investigated, using models such as (27); the gauche-y shift of the PO(OMe), group was found to be ca. 2 ~ . p . m . ~ ~ Hydrogen-I. The HA signal of the cyclic phosphonates (28) moved upfield to 6 6.2 p.p.m. when the N-aryl ring possessed two ortho-methyl groups.48The shielding effect is even larger for the phosphorane (29), and HA appeared at 6 5.9 p.p.m.

Studies of Equilibria and Shift Reagents.-N.m.r. studies of the exchange of halogen in boron trihalide adducts of trimethylphosphine, its oxide, and ~ u l p h i d e and ,~~ exchange of chloro- and methoxy-groups between methylphosphino and methyl-silyl or -germyl moieties,6ohave been reported. The rates of ionization of phosphoranes 45 46

47 48

49 50

J. R. Wiseman and H. 0. Krabbenhoft, J. Org. Chem., 1976,41, 589. T. A. Albright, S. V. Devoe, W. J. Freeman, and E. E. Schweizer, J. Org. Chem., 1975,40,1650 G . W. Buchanan and C. Benezra, Canad. J. Chem., 1976,54,231. J. I. G. Cadogan, D. S. B. Grace, and B. S. Tait, J.C.S. Perkin Z, 1975, 2386. M. J. Bula and J. S. Hartman, Canad. J . Chem., 1975, 53, 326. K. M. Abraham and J. R. Van Wazer, J . Znorg. Nuclear Chem., 1975, 37, 541.

0rganophosphor us Chemistry

254

such as (30) cannot be determined directly since the salt (31; X = PhO) is not observed in the n.m.r. However, lineshape analysis of the spectrum of a 1 :1 mixture of (30) and (31 ; X = S03CF3)allowed the equilibrium rates to be calculated over a range of temperatures. It was also shown that very fast or-proton +/

MeP(OPh),

MeG(OPh), X-

CH,P-OPh \Y

I’h,$NH ArO-

exchange via ylide intermediates (32) was also occurring. Similar intramolecular A general computer reactions of imino-compounds (33) have also been program has been developed for n.m.r. lineshape analysis of intermolecular exchange in non-first-order multi-spin The program gives detailed mechanistic information. Equilibrium mixtures of condensed phosphates have been studied.54 Shift reagents have been used for the configurational and conformational analysis of cyclic phosphites (34).55 The reagent Eu(fod), moved HA of the vinylphosphine oxide (35) twice as far downfield as the corresponding proton in the spectrum of the

Z - i ~ o m e rThe . ~ ~isomers of the cyclic phosphonate (36) were assigned from the effect of Eu(dpm), on the methyl signal.57Shifts of the butyl signals of tributyl phosphate by europium chloride have also been recorded.58 Pseudorotation.-A number of spirocyclic phosphoranes possess square-pyramidal structures rather than the trigonal-bipyramidal structures previously assumed, and this could have important consequences on the interpretation of their variabletemperature spectra. There is, as yet, no evidence that acyclic or monocyclic phosphoranes favour the square-pyramidal geometry, and the variable-temperature lH 51 52 53

54

55 56

57 58

D. I. Phillips, I. Szde, and F. H. Westheimer, J. Amer. Chem. Sac., 1976, 98, 184. H. €3. Stegmann, G. Bauer, E. Breitmaier, E. Herrmann, and K. Schemer, Phosphorus, 1975,5, 207. A. D. English, P. Meakin, and J. P. Jesson, J. Amer. Chem. SOC.,1976, 98, 414, 422. M. Watanabe, Chubu Kogyo Daigaku Kiyo, 1973,9, 73; W. E. Morgan, T. Glonek, and J. R. Van Wazer, Znorg. Chem., 1974, 13, 1832; A. J. R. Costello, T. Glonek, T. C. Myers, and J. R. Van Wazer, ibid., p. 1225. Yu. Yu. Samitov, A. A. Musina, L. I. Gurarii, E. T. Mukmenev, and B. A. Arbuzov, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1407. H. Koeppel, U. Lachmann, and K. D. Schleinitz, J. prakt. Chem., 1975, 317, 425. M. V. Sigalov, V. A. Pestunovich, V. 1. Glukhikh, M. Ya. Khil’ko, V. M. Nikitin, M. F. Larin, and B. A. Trofimov, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1645. V. Yastrebov, 0. V. Galaktionova, E. N . Lebedeva, and S. S. Korovin, Zhur. neorg. Khim., 1974, 19, 1252.

Physical Methods

255

and 19Fn.m.r. spectra of difluorophosphoranes such as (37), which contain fourmembered rings, indicate that the pseudorotation processes are between t .b.p. structure^.^^ The lH, I3C,and l91F n.m.r. spectra of the metliyltrifluorophosphoranes (38) also indicated that the molecules have t.b.p. structures, but in this case there was

no evidence for pseudorotation below 100 0C.60 Steric effects had an important influence on the pseudorotational barriers of the oxyphosphoranes (29; Y = Me, Ph, or OR), and substitution of the N-phenyl group by N-mesityl increased AG* by 7 to 11 kJ rn01-l.~~The stereoisomerism and pseudorotation of some spirophosphoranes (39) have also been studied.6f Non-equivalence, Inversion, and Medium Effects.-The n.m.r. spectra of the phosphonates (40; Y = CHRCOX) have been investigated in isotropic and anisotropic solvents, and diastereoisomeric anisochronism has been detected.62Low barriers to inversion were found for the diphospholan (41) and diphosphorinans (42) when the bridging group E was changed from carbon to germanium, silicon, or tin.63Dipolar couplings were obtained from the n.m.r. spectra of sodium methylphosphonate (43)

dissolved in a lyotropic liquid crystal; the molecular orientation and bond lengths were estimated.64Similar studies have been carried out on phosphorus oxytriSpin-Spin Coupling.-The relative roles of different coupling mechanisms in organophosphorus compounds have been studied theoretically.6 6 The spin-spin interaction constants for methylphosphine have been calculated by the MO-LCAO method.67Unresolved isotropic coupling to boron caused broadening of the vinyl 59

6o 61 62 63 64

65 66

67

N. J. De’Ath, D. B. Denney, D. Z. Denney, and Y. F. Hsu, J. Amer. Chem. Soc., 1976,98,768 K. I. The and R. G. Cavell, J.C.S. Chem. Cornm., 1975, 716. B. A. Arbuzov, Yu. Yu. Samitov, Yu. M. Mareev, and V. S. Vinogradova, Doklady Akad. Nauk. S.S.S.R., 1972, 205, 1370. M. I. Kabachnik, E. I. Fedin, L. L. Morozov, A. E. Shipov, M. S. Vaisberg, P. V. Petrovskii, and T. A. Mastryukova, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1418. A. Hauser, A. Zschunke, K. Issleib, and W. Bottcher, Phosphorus, 1975, 5, 261. R. C. Long, jun. and J. H. Goldstein, MoZ. Phys., 1975, 30, 681. P. K. Bhattacharyya and B. P. Dailey, MoZ. Phys., 1974, 28, 209. R. Kh. Safiullin, Yu. Yu. Samitov, and R. M. Aminova, Sbornik Aspirantsk. Rabot., Kazan. Un-T. Tochn Nauki Fiz., 1974, 175 (Chern. Abs., 1976, 84, 3962). R. Kh. Safiullin, R. M. Aminova, and Yu. Yu. Samitov, Zhur. strukf. Khinz., 1974, 15, 907.

Organophosphorus Chemistry

256

proton resonances of the trivinylborane-trimethylphosphine adduct rather than quadrupole relaxation effects.6 8 The PH dipolar splitting of solid potassium dihydrogen phosphate has been resolved by a multiple-pulse m e t h ~ d .The ~ sterochemistry of the cyclicphosphite (34) and analogous compoundshas been investigated,using the Overhauser effect,55and 13C hydrogen-satellite spectra were used to determine the structure of the vinylphosphine (44).70

JPPand JPM.Replacement of methyl by t-butyl in tetra-alkyldiphosphines (45) leads to very large negative increments in ~JPP, i.e. from - 179.7 Hz for (45; R = Me) to

-45 1 Hz for (45 ;R = But), which is due to rehybridization rather than a change in conformational populations.71 The changes are rationalized by increases in the bond angles, which reduce the s-character in the hybrid orbitals used to form the n-bond between the two phosphorus atoms. The catenated phosphorus dianions such as the disodium and dipotassium tetraphenylphosphines (46) give spectra with positive and temperature-dependent P-P coupling constants in accordance with the cyclic structures shown.72The direct P1I1-PIV coupling constant for the phosphinophosphinimines (47) was found to increase with decreasing basicity of the N Y As with the diphosphines above, t-butyl groups also greatly increase the magnitude of ~JPP in the disulphides (48).22c* 74 The mixed chalcogenides (49a; R = C,Hll) and (49a; R = But) had lJpp values of 175 and 149.5 Hz re~pectively.~~ The spectra of 0

R

I

R,,P-P=NY

I

R (47)

s s

II II &P -PK, (48)

s o

II II

R,P -P(OMe), (494

(49b)

0

phosphinomethylphosphine sulphides have been studied 76 and 3 J for ~ the ~ ethylene derivatives (49b) has been estimated from linewidths.7 7 Further examples of larger one-bond coupling to equatorial atoms compared to axially orientated atoms have 68 69 '0

71 72

73

74 75 76

77

L. W. Hall, J. D. Odom, and P. D. Ellis, J . Organometallic Chem., 1975, 97, 145. U. Burghoff, H. Rosenberger, R. Zeiss, R. Mueller, and L. N. Rashkovich, Phys. Status Solidi (A), 1974,26, K171. M. L. Sheer, Org. Magn. Resonance, 1974, 6, 85. H. C. E. McFarlane and W. McFarlane, J.C.S. Chem. Comm., 1975, 582. P. R. Hoffman and K. G. Caulton, J. Amer. Chem. SOC.,1975,97, 6370. H. Rossknecht, W. P. Lehmann, and A. Schmidpeter, Phosphorus, 1975,5, 195. Note that ~ J Pof P (40; R = Me) is misquoted on p. 261 of ref. 2212; the correct value is 18.7 Hz. K. M. Abraham and J. R. Van Wazer, Phosphorus, 1975,6, 23. J. D. Mitchell, Dim. Abs. Internat. (B), 1975, 36, 2212. Yu. Yu. Samitov, E. A. Berdnikov, F. R. Tantasheva, B. Ya. Margulis, and E. G. Katatv, J. Gen. Chem. (U.S.S.R.), 1975,45, 2097.

Physical Methods

257

appeared,lJpsebeing 909 Hz for (50), but 883 Hz for the alternative stereoisomer with an axial selenium atom.78 JPC. The selenide (50) and the cyclic phosphonate (51) show larger ~ J P values C to the 79 equatorial carbon atoms than to the axial carbon atoms in the other thus the coupling is 145.0 Hz for (51) but only 132.8 Hz when the methyl group is

axial. It is deduced from the P-C coupling constants from the low-temperature spectra of tetra-alkyldiphosphines (45) that NPC(i.e. ~ J P+ C*JPc)is large when the P--C bond is trans to the phosphorus lone-pair of electrons, as shown in (52), and small when the P--C bond is gauche to the lone pair of electrons, as shown in (53).80 For the diphosphine (45; R = But) it is deduced that NPCis 45.5 Hz for the bond in the tramorientation and 1 Hz for the bond in the gauche-orientation. It is interesting to note that the geminal PCC coupling constant of dichloro-t-butylphosphine (54), measured at - 140 "C, is at a minimum (0 Hz) when the C-C bond is trans to the phosphorus lone-pair of electrons and at a maximum (31.5 Hz) when the C-C bond is gauche to the lone-pair of electrons.81The appearance of averaged coupling constants for isopropyldichlorophosphine (55; R = Me, JPC= 17.5 Hz) and

ethyldichlorophosphine (55; R = H, a J p ~= 13.6 Hz) indicates that the conformers with a methyl group trans to the lone-pair of electrons predominate in a rapidly interconverting conformational equilibrium. The signs and magnitudes of the one-, two-, and three-bond P-C couplings for a series of acetylenic phosphines (56) and some PIV derivatives (57) have been described.82In contrast to the PIV derivatives, orbital coupling and/or spin dipolar mechanisms are probably dominant for the phosphines, due to the negligible s-character in the P - C bonds. The vicinal POCC coupling constants for the phosphite (58; Y = SMe)85and the amino-compound (58; Y = N H B u ~ )in , ~the ~ cis configurations shown, are over double those when the group Y is axial. The similarity of the PC coupling constants (50-65 Hz) of certain methylphosphonium halides and the reagents produced by the action of organolithium 78

79 80

81 88

8s

W. J. Stec, K. Lesiak, D. Mielczarek, and B. Stec, Z . Naturforsch., 1975,30b, 710. K. Lesiak, B. Uznanski, and W. J. Stec, Phosphorus, 1975,6, 65. R. K. Harris, E. M. McVicker, and M. Fild, J.C.S. Chem. Comm., 1975, 886. J. P. Dutasta and J. B. Robert, J.C.S. Chem. Comm., 1975, 747. R. M. Lequan, M. J. Pouet, and M. P. Simonnin, Org. Magn. Resonance, 1975,7, 392. A. Okruszek and W. J. Stec, 2.Naturforsch., 1975,30b, 430.

258

OrganophosphorusChemistry

compounds is attributed to the formation of lithium adducts (7) rather than ylides (8). Methylene ylides prepared by other methods give ~ J P values C in the region of 90-100 H z . ~ The ' P-C couplings through 1-5 bonds of model phosphonates such as (59) and (27) show that the vicinal coupling constants are at a maximum when the bonds are orientated at 180"and severely attenuated by OH substitution, especially when the hydroxy-group is trans-coplanar to the C-terminus of the coupling path. When a cyclopropyl group is part of the CCCP pathway, the coupling constants are much less than those predicted on the basis of dihedral angle. A highly asymmetric dihedral dependence of the vicinal couplings has been suggested. Some long-range C-P couplings through saturated bonds have been found which do not follow a W path.47 JPC,H.The geminal PCH coupling constants of the phosphinoacetonitriles (60) decrease with an increase of the bulk of the alkyl groups; thus 2 J is 5.1 ~ Hz~ for ~ (60; R = Et) and 2.1 Hz for (60; R = But).84The corresponding oxides have

larger coupling constants, 14.2 and 12.6 Hz respectively, the trend in magnitude being the same as in the phosphines. MO-LCAO calculations on the oxides (61) indicate that JPCH is dependent on the orientation of the HCPO bonds. The calculated values varied from 10 to 16 Hz for (61 ;Y = Me) and a remarkable 3 to 31 Hz for (61; Y = Cl).85The CNDO-CP method gave coupling constants closer to a normal Karplus relationship than those deduced experimentally from rigid molecules, whereas the reverse applied when the Pople-Sanky approximation was used. The n.m.r. parameters of thiocarbonyl-stabilized ylides (62; JPCH25-30 H z ) , ~ ~ acrylylphosphonates (63 ; JPCH 14.8-17.5 H z ) , ~propenylphosphonates ~ (64; JPCH

84

85 86

87

0. Dahl and F. K. Jensen, Acta Chem. Scand. ( B ) , 1975,29, 863. Yu. Yu. Samitov, R. Kh. Safiullin, R. M. Aminova, N. D. Chuvylkin, and G . M. Zhidomirov, Phosphorus, 1975, 5, 151. H. Yoshida, H. Matsuura, and T. Ogata, Bull. Chem. Soc. Japan, 1975,48, 2907. F. H. Meppelder and H. C. Beck, Rec. Trav. chim., 1975, 94, 149.

Physical Methods

259

~ ~the cycliccompound (65;JPCH 12 Hz) have been reported. Four-bond 17 H Z ) ,and couplings of 1 and 3 Hz are reported for the propenylphosphonates (64).88 JPNH. The magnitude of geminal PNH coupling constants can vary extensively: e.g. 6 Hz for the phosphonamide (66)yg09-12 Hz for secondary amides and phosphoroamidates, and 29-33 Hz for the phosphorylhydrazides (67).91

JPXGH.The POCH coupling constants of a variety of phosphites and thiophosphatesg2 and cyclic phosphatesg3have been reported. The use of these coupling constants for conformational analysiscontinues,and reports on derivatives of oxazaphospholan (68),04 dioxaphosphorinans (69),06 1,4,2-oxazaphosphorinans (70),06 and the first representatives of dithia- and diaza-phosphorinans (71;X = S or NH) have been published. Long-range PCNCH coupling constants of 1.46 and 1.80Hz have been recorded for (70;Y = OPri; R = Ph).O6

R

I

‘P’

Y

I

NO*

Y

1

H

Nuclear Quadrupole Resonance Studies.-The 3sCl atoms of the chlorotriphenylphosphonium ion (72)have been assigned to the n.q.r. resonance at 31.15 MHz.07At 77 K the trichlorophosphinimines(73)give multiplets which reflect non-equivalence The 36Clfrequency arising from a small barrier to rotation about the P-N of the acid chlorides (74) and (75) rises about 1 MHz as the atomic weight of the L. Maier, Phosphorus, 1975, 5, 223. T. A. Mastryukova, Kh. A. Suerbaev, P. V. Petrovzkii, E. I. Fedin, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1974, 44, 2359. 90 M. J. P. Harger, J.C.S. Perkin I, 1974, 2604. 9 1 R. J. Cremlyn, J. David, and N. Kishore, Phosphorus, 1975, 5, 203. 92 R. Burgada, L. Lafaille, and F. Mathis, Bull. SUC.chim. France, 1974, 341. 93 F. Ramirez, S. L. Glaser, P. Stern, I. Ugi, and P. Lemmen, Tetrahedron, 1973, 29, 3741. 94 J. Devillers, M. Cornus, and J. Navech, Org. Magn. Resonance, 1974, 6 , 211. 95 B. A. Arbuzov, R. P. Arshinova, T. A. Guseva, T. A. Zyablikova, L. M. Kozlov, and I. M. Shermergorn, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1403. 96 Yu. Yu. Samitov, M. A. Pudovik, L. K. Kibardina, and A. N. Pudovik, J. Gen. Chem.

88 89

(U.S.S.R.),1975, 45, 2102. 97

98

E. E. Nifant’ev, A. A. Borisenko, A. I. Zavalishina, and S. F. Sorokina, Doklady Akad. Nauk S.S.S.R., 1974, 219, 881 ; K. B. Dillon, R. J. Lynch, R. N. Reeve, and T. C. Waddington, J. Znorg. Nuclear Chem., 1974, 36, 815. I. A. Kyuntsel, V. A. Mokeeva, G. B. Soifer, E. S. Koslov, and M. I. Povolotskii, J. Gen. Chem.

(U.S.S.R.),1975,45, 1954.

260

Organophosphorus Chemistry CN I

chalcogenide atom increases through oxygen and sulphur to selenium and also upon changing the structure from the monochlorides (74) to the dichlorides (75).@OThe effect of changing the nature of the group Y is basically inductive. A frequencytemperature equation has been developed for the n.q.r. spectra of the phosphadiazines (76) at 77-390 K.lo0

2 Electron Spin Resonance Spectroscopy The e.s.r. spectra of phosphorus compounds have been reviewed.lo1 The phosphorus hyperfine splitting ( a p 33.5 G )of the radical anion (77) is within the 25-36 G range of phosphorin radical anions.lo2 The cis- and trans-isomers of 1,Zbisdiphenylphosphinoethylene gave the same radical anion (78). The unpaired electron is coupled to all the protons in the molecule as well as to the two phosphorus atoms, and shows that the electron is completely delocalized. Only when caesium was used as the gegenion in THF could a metal interaction be detected. The spectrum in this case corresponded to the association of two caesium ions with the radical anion, the third

metal ion being separated.lo3The isotropic 31Phyperfine splittings of &substituted alkyl radicals (79) are in the order expected for hyperconjugative spin transmission for both PII1 and PIv compounds. The magnitude and temperature dependence of ~ Z H Sindicate that the conformation shown in (80) is the most stable.lo4The geometry of the alkylphosphine radical cations (81) is related to the electronegativity of the alkyl groups as in other trigonal radicals. Both the 31Phyperfine coupling constants and the ratios of the calculatedp- and s-spin densities correlated with SP of the respective neutral The triphenylphosphinium radical cation (81 ; R = Ph), generated by the X-irradiation of triphenylphosphine-trihalogenoborane 99

I. A. Nuretdinov, D. Ya. Osokin, and I. A. Safin, Bull. Acad. Sci. U.S.S.R.,1975,24, 263.

looE. A. Romanenko, Teor. ieksp. Khim., 1975,11, 705. 101 ‘Topics in Phosphorus Chemistry’, ed. E. J. Griffith and M. Grayson, Wiley, New York, 1975. 102 C. Jongsma, H. Vermeer, F. Bickelhaupt, W. Schafer, and A. Schweig, Tetrahedron, 1975,31,

293 1. 103

A. G. Evans, J. C. Evans, and D. Sheppard, J.C.S. Perkin 11, 1975, 643.

104

I. G. Neil and B. P. Roberts, J. Organometallic Chem., 1975, 102, C17. M. Iwaizumi, T. Kishi, and T. Isobe, J.C.S. Faraday 11, 1976, 72, 113.

105

PhyJical Methods

261

u R

K,P’

F

I4 0

adducts, has the odd electron mainly localized on the phosphorus atom.1°6 The mechanism of the reaction of t-butoxy radicals with dialkyl phosphites was studied by e.s.r. ~ p e c t r o ~ c o pThe y . ~ cc-proton ~~ hyperfine splittings (absent from deuteriated compounds) of the alkylphosphine dimeric radicals (82) indicated completely restricted rotation of the alkyl groups. The very large (58 G ) P-H isotropic constant observed in the spectrum of (83) has been attributed to the interaction of the unpaired electron with the antibonding a*-orbital of the P-P bond.lo8 The high temperature dependence of the 31Pcoupling constants of iminophosphorane radicals (84)is probably due to restricted rotation about the P-N bond; the splitting is described by a supposition of 226 and hyperconjugative interactions with the free According to the e.s.r. spectra of the radicals (85) and (86), the phosphorus ligands are non-equivalent ;calculations suggest that this is due to a distorted t.b.p. structure with the unpaired electron in a radial orientation. UHF and CND0/2 calculations indicate that the barriers to pseudorotation are very much higher for phosphoranyl radicals than for phosphoranes, e.g. 25.2 kcal mol-l for (87), 26.3 kcal mol-1 for (88), cf. 3.6 kcal mol-1 estimated for phosphorus pentafluoride. The high barriers appear to arise from a high p-character of the radial bonds, which leads to increased rigidity of these bonds. The calculations indicate that for electronegative ligands the orbital of the odd electron has a large contribution from the phosphorus s and p z electrons, but that for ligands of low electronegativity the s spin density decreases and the px density increases.11o The e.s.r. spectra of y-irradiated diethyl phosphate and its salts have been studiedlll and the structuresof the phosphonates(89) 112 and somenucleoside phosphates113have been studied from the e.s.r. spectra of the nitroxide spin-labelled compounds. An e.s.r. study of electron transfer in dinucleoside phosphate anions indicates preferenlo6 T.

Berclaz and M. Geoffroy, Mol. Phys., 1975, 30, 549. G. Brunton and K. U. Ingold, Org. Magn. Resonance, 1975, 7 , 527. lo8 M. Iwaizumi, T.Kishi, F. Watari, and T. Isobe, Bull. Chem. SOC.Japan, 1975, 48, 3483. log K. Scheffler, S. Hieke, R. Haller, and H. B. Stegmann, Z . Naturforsch., 1975, 30a, 1175. Yu. I. Gorlov and V. V. Penkovsky, Chem. Phys. Letters, 1975, 35,25; V. V. Penkovsky and Yu. I. Gorlov, V. Sb., Kuant. Khimiya, 1975,191 (Ref. Zhur., Khim., 1975, Abstr. No. 23B73). ll1 F. S. Ezra, Nuclear Sci. Abs., 1974, 29, 20688. 112 A. V. Il’yasov, Ya. A. Levin, A. Sh. Mukhtarov, and M. S. Skorobogatova, Teor. i eksp. Khim., 1975, 11, 612. 113 A. I. Petrov and B. I. Sukhorukov, Biofizika, 1975, 20, 965.

lo’

10

262

Organophosphorus Chemistry

tial protonation of thiamine in the DMP anions.114y-Radiolysis of deoxythymidine monophosphate gave very complex spectra, requiring computer-assisted ana1~sis.l~~ Phosphate deposits in liver mitochondria have been analysed with the aid of e.s.r.ll* and the spectra of some dihalogenophosphinidine radicals have been ana1y~ed.l~’ 3 Vibrational Spectroscopy Band Assignment and Structural Elucidation.-The infrared and Raman spectra of dimethylphosphine and its deuterium analogue (90) were determined in all phases. The PH stretching and bending regions gave some evidence of weak hydrogen bonding, and torsional modes gave barriers of 2.14 and 2.30 kcal mol-1 for the hydrogen and deuterium compounds respectively.l18 The PN stretching frequency around 900 cm-l for the phosphoramidates (91 ;Y = H, C1, or Me) was identified by 15N isotopic substitution; it was found that the F=O and P-N bond orders varied in a manner similar to the corresponding bonds in carboxamides, which was interpreted in terms of substantial p,-d, bonding.llg The i.r. spectra of carbamoyltriphenylphosphoranes (92; R = H, D, or Me) show bands at 1183i-4 cm-1 which are

assigned to YPN. The carbonyl group has an insulating effect, for the band position varies far less than it does in the phosphinimines (93; R = H, Me, or Ph).120 The i.r. band intensities of the phosphonium cobaltates (94; X = CoHal,) are five times greater than those of the corresponding phosphonium halides.121The structures of 1,3-thiaphosphetans(95) 122 and the cyclic phosphonic anhydride (96) 123 have been studied. The spectra of dichloromethylphosphonic acid (97), and its salts, in water

M. D. Sevilla, R. Failor, C. Clark, R. A. Holroyd, and M. Pettei, J. Phys. Chem., 1976,80,353. S . Gregoli, M. Olast, and A. Bertinchamps, Radiation Res., 1976, 65, 202. 116 K. Ostrowski, A. Dziedzic-Goclawska, A. Sliwowski, L. Wojtczak, J. Michalik, and W. Stachowicz, F.E.B.S. Letters, 1975, 60,410. 1 1 7 A. J. Colussi, J. R. Morton, K. F. Preston, and R. W. Fessenden, J. Chem. Phys., 1974, 61, 1247. 118 J. R. Durig and J. E. Saunders, J. Raman Spectroscopy, 1975, 4, 121. 119 Yu. P. Egorov, Yu. Ya. Borovikov, E. P. Kreshchenko, A. M. Pinchuk, and T. V. Kovalevskaya, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1683. 120 W. Buder and A. Schmidt, Spectrochim. Acta (A), 1975,31, 1813. 1 2 1 M. A. A. Beg, Q. M. Samiuzzaman, and M. Jamal, Proc. Pakistan Acad. Sci., 1974, 11, 57. l Z 2R. R. Shagidullin and I. Kh. Shakirov, Spectroskopiya i Ee Primenenie V. Geojizike i Khimii, 1975, 231 (Chem. A h . , 1976, 84, 43129); I. Kh. Shakirov and R. R. Shagidullin, Doklady Akad. Nauk S.S.S.R., 1974, 219, 917. lZ3L. Maier, Phosphorus, 1975, 5, 253. 114

115

Physical Methods

263

and deuterium oxide have been assigned, and the force constants ~a1culated.l~~ It has been shown that laser Raman spectroscopy provides a far simpler method than tritium labelling for determining the rate constant of C-8-proton exchange in purine nucleotides. It also makes feasible the study of comparative rates of exchange in different nucleic acids to reveal differences in secondary Reduction of trimethyl phosphiteborane is believed to give a new type of diphosphorane (98), possessing YPP 437 cm-1.126 Stereochemical Aspects.-The i.r. and Raman spectra of ethylphosphine and its deuteriated analogue (99) indicate that the fluid phases contain gauche- and transconformers, but the solid phase contains the trans-conformer only. The methyl

II

YJ’ CH,CD,PH,

\

/I1

/C=YOLt

11

S

II

C1,POMe

rotational barrier is estimated to be 3.74 kcal m ~ l - ~The . ~ ~doublet ’ nature of YC=C in the spectra of vinyl-phosphonic and -phosphonous acids (100) has been attributed to rotational isomerism around the =C-0 bond.128The calculated band frequencies for the gauche- and trans-conformers of methyl ester (101) were close to the experimental ~ a 1 u e s .Conformational l~~ analysis of dialkyl and diary1 phosphites (1 02) by the combined i.r. and dipole-moment method has been reported. It was also deduced that P--He .O=P hydrogen bonding was absent.130 The ratio of tgg and ggg conformers of trialkyl selenophosphates (103) in hexane and acetonitrile solutions has been determined131and the dichloride (104) shown to exist mainly in the gaucheconformation when dissolved in non-polar media.132

124 125 126

127 128

129 130 131 132

B. J. Van der Veken and M. A. Herman, J. Mol. Structure, 1975,28, 371. J. Livramento and G. J. Thomas, jun., J . Amer. Chem. SOC.,1974,96, 6529. L. A. Peacock and R. A. Geanangel, Inorg. Chem., 1976,15, 244. J. R. Durig and A. W. Cox, jun., J. Chem. Phys., 1975, 63, 2303. A. V. Chernova, G . M. Dorozhkina, R. R. Shagidullin, V. V. Maskova, and G. F. Nazvanova, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1871. R. R. Shagidullin, 0. A. Raevskii, and I. I. Vandyukova, Bull. Acad. Sci. U.S.S.R., 1975,24, 71. 0. A. Raevskii, Yu. A. Donskaya, F. G . Khalitov, E. L. Vorkunova, and Ya. A. Levin, Phosphorus, 1975, 5, 241.

R. R. Shagidullin, I. I. Vandyukova, I. A. Nuretdinov, and Kh. Kh. Davletshina, Doklady Akad. Nauk S.S.S.R., 1975,225, 886. R. R. Shagidullin, I. A. Vandyukova, and 0. A. Raevskii, Bull. Acad. Sci. U.S.S.R.,1975,24, 1414.

264

Organophosphorus Cheniistry

Studies of Bonding.-Hydrogen bonding of phenol or t-butyl alcohol to the phosphonates (105) has been studied. The hydrogen bond remained with the phosphonyl group when the group R contained nitrile or carboxylic ester groups. The AH values correlated with the Taft constants better than with d ~ and , this was attributed to d, bonding influencing BP where this was p0ssib1e.l~~ The YOH bands of a-hydroxy compounds such as the phosphonamide (106) have been analysed in terms of intermolecular hydrogen-bonded A ring-chain tautomeric equilibrium

between the Pv spirophosphoranes (107) and the PIII open-chain form (108) has been established and phosphorus-hydrogen bonding studied.1351.r. studies indicate that the stability of the iminophosphorane (109) over its methylenephosphorane tautomer (1 10) increases as the electron-withdrawing properties of the group R are Calculations on the tautomerism of the cyanoacetic ester derivatives (1 11) indicated that the inductive effect of the R groups had a dominating

plit RN-P-CII

013

,C02Et

I

RNH--P=C

/Co2E1

(K'O), I'C H

4 Microwave Spectroscopy The microwave spectra of ethylphosphine and its deuteriated analogues (1 12) and (113) show the presence of gauche- and trans-conformers in a ratio of 45 :55. Dipole moments, bond lengths, bond angles, and dihedral angles have been calculated for each conformer.138

5 Electronic Spectroscopy Absorption.-U.v, spectroscopy has been used to study the structure of the orange dianions (114). Plots of B against l/(rc 2) for each cation gave straight lines at 20 and

+

133 134 135 l36 137 13*

V. E.Bel'ski, R. F. Bakeeva, L. A. Kudryavtseva, A. M. Kurguzova, and €3. E. Ivanov, J. Geiz. Chem. (U.S.S.R.), 1975, 43, 2568. R. R. Shagidullin and E. P. Trutneva, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1637. R. Mathis, M. Rarthelat, Y . Charbonnel, and J. Barrans, Compt. rend., 1975, 280, C , 809. 0.I. Kolodyazhnyi, J. Gen. Chem. (U.S.S.R.), 1975, 45, 539. M.Kirilov, G.Petrov, N. Tyutyulkov, and Y. Yotov, Munatsh., 1975, 106, 1533. J. R. Durig and A. W. Cox, jun., J, Chem. Pirys., 1976, 64, 1930.

265

Physical Methods

1 0 0 "C, showing that the anions and cations exist as contact ion pairs.1o3The possibility of p , d , conjugation in arylphosphines has been discussed in terms of overlap integrals and the energies of planar and pyramidal forms.139 Free-electron MO calculations have been applied to the absorption frequencies of unsymmetrical phosphocyanines derived from cyclopentadienylidenetriphenylphosphorane (1 1 5).140 Ar

A study of the influence of the Y substituents on the U.V. spectra of the phosphonium ylides (1 16) and the phosphinimines (1 17) indicated that the transmission factor of the group C,H4P=CH is less than half that of C6H4P=N,which itself is 10-20 times lower than C6H4.141Varying the nature of Z in the phosphinimine (118) had an irregular effect on the anionic chromophore, and a linear relationship between Ymax and Ed is not The effect of varying the nature of the phosphorus substituents Y in the vinyl compounds (100) has been described. It is interesting to note that although the PIv groups are probably the best electron-withdrawing groups to place opposite the donating ethoxy-group, the PII1dichloride (1 19) possesses the best chromophoric propert ies.12* Photoelectron.-n-Orbital energies appear to be unsuitable to discern the aromatic nature of phospholes (120) due to combined nn* and n, interactions. It is concluded that It,* conjugative and P-C,* hyperconjugative interactions stabilize the phosphole system relative to the interrupted cis-butadiene and phosphorus subunits, and that the p.e. spectrum can be interpreted in favour of an aromatic phosphole ring.143 Other workers have and reviewed 145 this aromaticity problem, and there has been a quantum-chemical study of the aromatic nature of phosphorus heteroc y c l e ~ The . ~ ~p.e. ~ spectrum of the ylide (121) contains peaks at 6.19, 8.32, and 139 140

141 142 143 144 145 146

E. N. Tsvetkov, J . Gen. Chem. (U.S.S.R.),1975,45,489. M.K.Rout and L. N. Patnaik, 2.phys. Chem. (Leipzig), 1975,256,785. R. I. Yurchenko, 0. M. Voitsekhovskaya, I. N. Zhmurova, and N. N. Lysova, J . Gen. Chem. (U.S.S.R.), 1975,45, 1700. I. N. Zhmurova and V. G . Yurchenko, J. Gen. Chem. (U.S.S.R.), 1975,45,1924. W.Schaefer, A. Schweig, and F. Mathey, J. Amer. Chem. Soc., 1975,98,407. G.V. Bakulina, Yu. S. Mardashev, and E. V. Borisov, Primenenie Konformatsion. Analiza V Sinteze Novykh Organ. Veshchestv., 1975,66 (Ref. Zhur. Khim., 1975,Abs. No. 20ZH45). A. N. Hughes and D. Kleemola, J. Heterocyclic Chem., 1976,13, 1. E. D. Lavrinenko-Ometsinskaya, V. V. Pen'kovskii, V. V. Strelko, T. L. Krasnova, E. F. Bugarenko, and E. A. Chernyshev, Koant. Khimiya, 1975 L-147 ( R e 5 Zhur., Khitn., 1975, Abs. No.22B60).

Organophosphorirs Chemistry

266

8.90 eV; the inductive effect of the carbanion shifts the nas band of benzene (which has its nodal plane passing through the substituent site) from 9.24 to 8.32 eV whilst the other two bands originate from the interaction of the ZC- carbanion orbital [which is at 6.81 eV for the methylene ylide (122)] with the nsorbital of benzene. The ns + nc- band, which would normally appear at a higher value than 9.24 eV, is also influenced by a strong inductive effect and appears at 8.90 eV. Similar effects occur for the corresponding iminophosphorane, but all three bands appear at higher eV va1~es.l~’ 6 Rotation The optical purity of the phosphonate (123)148and the absolute configuration of the phosphonium bromide (124) 149 have been established. Optical rotatory dispersion and circular dichroism have been used in stereochemical studies of phospholipids 150 and adeno~ine-5’-triphosphate.~~~ 0

I/

(E t O), P<’HI’h NH,

Me,

Ph4‘P+-

/

PhCH,

a-CJ I,

Br-

7 Diffraction X-Ray.-The crystal and molecular structure of tri-o-tolylphosphine, its oxide, sulphide, and selenide (125) have been compared. The mean P-C bond lengths appear to be determined by the 0-electron density along the P-C bond and intramolecular steric interactions. d-Orbital participation was considered to be of little X-Ray diffraction established the structure of diphosphinofumarate (126)153and showed that the phospholanium iodide (127) has an envelope ring with the methyl group at the point of the flap.lS4The bicyclic phosphonium bromide (128) has a distorted half-chair phosphorus-containing ring, one of the P-C bonds in the 147

K.H.A. Ostoja Starzewski, H. Bock, and H. Dieck, Angew. Chem. Znternat. Edn., 1975, 14,

173. Yu. P. Belov, V. A. Davankov, V. A. Tsyryapkin, and S. V. Rogozhin, Bull. Acad. Sci. U.S.S.R., 1975, 24, 1505. 149 R. Luckenbach, Chem. Ber., 1975, 108, 3522. 150 1. A. Vasilenko, G . A. Serebrennikova, and R. P. Evstigneeva, Bio-org. Khim.,1975, 1, 1307; H. Akutsu, Y. Kyogoku, H. Nakahara, and K. Fukuda, Chem. and Phvs. Lipids, 1975, 15, 2 2 2 ; S. G . Batrakov, A. G . Panosyan, G . A. Kogan, and L. D. Bergel’son, Bio-org.Khim., 1975, 1,1593. 151 T.J. Gilligan and G. Schwarz, Biophys. Chem., 1976, 4 , 55. l S 2 T. Cameron and B. Dahlen, J.C.S. Perkin IZ, 1975, 1737. lS3 D. Fenske and J. Loens, Clzern. Rer., 1975, 108, 3091. 15* A, Fitzgerald, G. D. Smith, C. N. Caughlan, K. L. Marsi, and F. B. Burns, J . Org. Chem,, 1976, 41, 1155. 14*

Physical Methods

267

ring being only 177.1 pm.155Thi~cann~t bedueto n-bonding, and inthecyclicsalt(129) the P-C bond involving the sp2 carbon is longer (179.9 pm) than the P-C bond involving an sp3 carbon (178.8 pm). In this case the heterocyclic ring has a nearperfect half-chair c ~ n f o r m a t i o nIt . ~is~ ~interesting to note that even in the phosphonium ylides it is possible to explain the short P-C bond lengths without recourse to d,-p, bonding.29The (+ )-phosphoniumbromide (130) has been shown to have the R configuration.15 The structures of the salts (1 31) 15* and (1 32),159a chelated ylide,lsoand the insecticide coroxonlsl have been determined. The structures of the cis- and trans-isomers of the cyclic phosphonamide (133) differed in that the cis-isomer has a half-chair conformation whereas the trans-isomer has an envelope conformation. Both compounds had hydrogen bonds of approximately 269 pm.lS2The phosphadiazane (1 34)

provides one of the rare examples of a cis-l,4-disubstituted cyclohexane derivative that exists in the twist conformation; the trans-isomer has a slightly flattened chair conformation.la3 The dioxaphospholan (1 35) has a semi-chair conformation; the S. R. Holbrook, D. van der Helm, W. Taylor, R. W. Chesnut, N. N. Durham, M. L. Higgins, T. E. Snider, and K. D. Berlin, Phosphorus, 1975, 6, 7. 156 S. R. Holbrook, M. Poling, D. van der Helm, R. W. Chesnut, P. R. Martin, N. N. Durham, M. L. Higgins, K. D. Berlin, and W. R. Purdum, Phosphorus, 1975, 6, 15. 157 R. Boehme, H. Burzlaff, M. Gomm, H. J. Bestmann, and R. Luckenbach, Chem. Ber., 1975, 108, 3525. 158 H. J. Lindner and B. Kitschke-von Gross, Chem. Ber., 1976, 109, 314. 159 H. Schaefer and A. G. MacDiarmid, Inorg. Chem., 1976,15, 848. 160 H. Takahashi, Y. Oosawa, A. Kobayashi, T. Saito, Y. Sasaki, and Y. Sasaki, Chem. Letters, 1976, 15. M. R. Gifkins and R. A. Jacobson, J. Agric. Food Chem., 1976,24,232. l e 2 V. D. Cherepinskii-Malov, V. G. Andrianov, F. H. Mukhametov, and Yu. T. Struchkov, Bull. Acad. Sci. U.S.S.R., 1974, 23, 1956. le3 U. Engelhardt and H. Hartl, Angew. Chem. Internat. Edn., 1975, 14, 554. 155

Organophosphorus Chc mistry

268 HO

II

0

II

OCf I=CHOP(OMe),

P-S bond is elongated to 196.5 pm and the P-O(H) bond shortened to 148 pm.ls4 The structures of the cis-vinyl carbonate (1 36) 165 and the cyclic phosphonic anhydride (96)123have been determined, and for the latter compound the ring was found to be almost planar. X-Ray diffraction data of deoxyuridine phosphate,ls6 phospholipid m u l t i l a y e r ~nucleotides,168 ,~~~ and skeletal have been analysed. The crystal structure of the phosphazene (137) has been e~tab1ished.l~~ Several interesting five-co-ordinate phosphoranes have been studied. The monocyclic oxazaphosphorane (1 38) has a trigonal-bipyramidal structure with a planar heterocyclicring; the nitrogen atom is sp2-hybridizedand bears an aryl ring which is completely orthogonal to the second benzene ring.171The bicyclic system considerably distorts the thiazaphosphorane (139) towards a square pyramid; the P-S bond length, 218.7 pm, remains closer to that appropriate for an apical bond.172Two

PI1

I

Ph

164

165

M. Mikolajczyk, M. Witczak, M. Wieczorek, N. G. Bokij, and Yu. T. Struchkov, J.C.S. Perkin I , 1976, 371. Mazhar-Ul-Haque, C. N. Caughlan, G. D. Smith, F. Ramirez, and S. L. Glazer, J. Org. Chem. 1976,41, 1152.

166

167 168 169 170

171 172

M. A. Viswamitra, T. P. Seshadri, and M. L. Post, Nuture, 1975, 258, 542. P. B. Hitchcock, R. Mason, and G. G. Shipley, J. Mol. Biol.,1975,94, 297. D. M. L. Goodgame, I. Jeeves, C. D. Reynolds, and A. C. Skapski, Biochem. J., 1975, 151, 467; M. A. Viswamitra, T. P. Seshadri, M. L. Post, and 0. Kennard, Nature, 1975,258,497. R. W. Lyinn, J. Mol. Biol., 1975, 99, 567. T. S. Cameron, Kh. Mannan, S. S. Krishnamurthy, A. R. Vasudeva Murthy, R. A. Shaw, and M. Woods, J.C.S. Chem. Comm., 1975,975. J. I. G. Cadogan, R. 0. Gould, S. E. B. Gould, P. A. Sodler, S. J. Swire, and B. S. Tait, J.C.S. Perkin I, 1975, 2392. J. I. G. Cadogan, R. 0. Gould, and N. J. Tweddle, J.C.S. Chem. Comm., 1975, 773.

Physical Methods

269

fused five-membered rings also distort the trigonal-bipyramidal structure, and in the oxazaphosphorane (140) the OPO bond is bent 8.4" and the two radial phenyl groups become non-equivalent. The P-N bond length lies between the ranges encountered for radial and apical P-N bonds and corresponds to a distortion towards structure (141).173As expected, pentaphenoxyphosphorane (142) has a near-perfect trigonalbipyramidal g e 0 m e t ~ y .The l ~ ~ effect of introducing two five-membered rings into the penta-oxyphosphorane system (143) is to distort it to that corresponding to a 15" turnstile rotation .l 75 Electron.-The determination of the molecular structure of phosphorus heterocycles by electron diffraction has been reviewed.17sThe structures of trimethylphosphine oxide, and the corresponding sulphide in the gaseous phase, have been compared. The rotational freedom of the methyl group appears to be greater for the sulphide, which also has the longer P--C bonds, i.e. 181.8 pm for (144; Ch = S) and 180.9 pm for (144; Ch = O).177The trifluoromethylphosphoranes (145) and (146) adopt the

stereochemistries shown.l7 8 This is an interesting finding because n.m.r. spectroscopy indicates that chlorine atoms are more apicophilic than trifluoromethyl groups in the presence of methyl or dimethylamino-gr~ups.~~~ The aliphatic chain packing in three crystalline polymorphs of a saturated racemic phosphatidylethanolamine has been studied.lsO 8 Dipole Moments, Permittivity, and Polarography The dipole moment of phosphabenzene is reinforced by the methyl group shown in (147) and increases it from 1.46 to 1.77 D; thus it resembles pyridine, which has the heteroatom at the negative end of the dipole.lsl The magnitudes and trends of the dipole moments of the methylphosphines have been investigated by MO studies and the dipoles partitioned into bond moments, bond polarization, and lone-pair moments.ls2The reciprocal effects of the double bond and the phosphorus atom in 173

W. S. Sheldrick, A. Schmidpeter,and J. H. Weinmaier, Angew. Chem. Znternat. Edn., 1975,14, 490. 1 7 4 R. Sarma, F. Ramirez, B. McKeevcr, J. F. Marecek, and S. Lee, J. Amer. Chem. SOC.,1976,98, 581. 1 7 5 R. Sarma, F. Ramirez, and J. F. Marecek, J. Org. Chem., 1976,41, 473. 1 7 6 V. A. Naumov, Kern. Kozlem, 1975,43, 5 1 1. 177 C. J. Wilkins, K. Hagen, L. Hedberg, Q. Shen, and K. Hedberg, J. Amer. Cheni. SOC., 1975,97, 6352. 178 H. Oberhammer and J. Grobe, 2.Nuturforsch., 1975, 30b, 506. 179 R. G . Cavell, D. D. Poulin, K. I. The, and A. J. Tomlinson, J.C.S. Chem. Comm., 1974, 19; D. D. Poulin and R. G . Cavell, Znorg. Chem., 1974, 13, 2324. 180 D. L. Dorset, Biochim. Biophys. Acta, 1976, 424, 396. 1 8 1 A. J. Ashe and W.-T. Chan, Tetrahedron Letters, 1975, 2749. 182 P. M. Kuznesof, F. B. T. Pessine, R. E. Bruns, and D. F. Shriver, Znorg. Chim. Acta, 1975,14, 271.

Organophosphorus Chemistry

270 Me

/

(147)

(148)

(149)

(150)

phospholens (148) and (149) have been studied. It is concluded that there is no p,, interaction of the phosphorus lone-pair of electrons with the double bond in (148) and that the electron-accepting properties of the phosphorus group predominate, regardless of its valency stafe.ls3 The dipole moment of the dioxaphosphorinan (150) corresponds to that calculated for the stereochemistry shown.ls4The moments of the isocyanates (1 5 1 ;Y = C1 or NCO) and the corresponding oxides have been used for their conformational analysis.lS5Variable-temperature dipole-moment studies of the methylphosphonates (152; Y = OPr) and the phosphonamides (152; Y = NHPr) have been interpreted in favour of hindrance to P-0 or P-N rotation. There

I/

C

II

0 (15 1)

(152)

(153)

(154)

appears to be an increase in the extent of rotation on substituting n-propyl by isopropyl in the esters, but not in the amides.186Studies of some stannyl thiophosphates (153)ls7 and phosphorus fluorideslSs have also been reported. Dipole moments, in combination with vibrational spectroscopy, have been used for the conformational analysis of a number of PIv c o r n p o ~ n d s . ~ ~ ~ - ~ ~ ~ Permittivity measurements have been used to study hydrogen bonding of phenol or carboxylic acids with trialkylphosphine oxides (154). The results can be explained in terms of a simple electrostatic model. The properties of trimethylphosphine oxide were different from the general properties of the Polarography has been used to study the structure of thiamine phosphateslgOand for the determination of phosphatase activity of milk.lgl 183

184 185 186

187 188 189 190

191

B. A. Arbuzov, A . 0. Vizel, V. K. Krupnov, and T. A. Zyablikova, Bull. Acad. Sci. U.S.S.R., 1975,24, 1883. B. A. Arbuzov, R. P. Arshinova, and E. T. Mukmenev, Bull. Acnd. Sci. U.S.S.R., 1974, 23, 2395. Yu. Ya. Borovikov, Yu. P. Egorov, V. A . Shokol, and L. I. Molyavko, J. Gen. Chem. (U.S.S.R.), 1975, 45, 2335. P. M. Zavlin. L. A. Ashkinazi, and V. M. Shek, J. Gen. Chem. (U.S.S.R.), 1975, 45, 226. E. A. Ishmaeva, R. A. Cherkasov, L. P. Ivantaeva, and I. V Bykova, J. Gen. Chem. (U.S.S.R.), 1975, 45, 457. R. G. Hyde, J. B. Peel, and K. Terands, J.C.S. Faraday ZZ, 1973, 69, 1563; A. J. van Straten and W. M. A. Smit, J. Mul. Spectroscopy, 1974, 53, 315. Yu. Ya. Borovikov, Yu. P. Egerov, and A. A. Matei, J. Gen. Chem. (U.S.S.R.), 1975,45,2563. N. N. Mosolov, Kokarboksilaza Drugie Tiamitifasfaty, 1974, 229, 241 (Chein. Abs., 1976, 84, 100 924). J. Davidek, P. Herman, and J. Seifert, Milchwissenschaft, 1376, 31, 76.

271

Physical Methods 9 Mass Spectrometry

The appearance potentials of HPCf and DPCf from methylidynephosphine (1 55) and its deuteriated analogue are close to the theoretical values.21The mass spectra and ion-molecule reactions of phosphiran (156) and of mixtures of phosphiran with ammonia and deuterio-ammonia show that all the important product ions are formed by PH group-transferreactions where ethane is generated as a neutral particle.

The molecular ion appears to retain its cyclic structure, but several ions with two or three phosphorus atoms can be detected.lg2The fragmentation patterns of a number of dialkylphosphines (157) show initial loss of an alkyl group as a neutral particle formed by the transposition of hydrogen.lg3Some six-membered cyclic phosphites (158 ;X = OEt, OPh, or C1) have been studied.lg4The mass spectra of a wide variety of phosphine sulphides (159; Z = Ph, Me, CH,Ph, COPh, NH2, N=CHPh, or

CH,SCH,) gave fragmentation patterns which indicate significant migration of phenyl and methyl from phosphorus to sulphur, as shown in the Scheme.lgsWhen

t .,SPh Ph P

R '

-

+

PhPK

--+

+ PhPE-CH

Scheme 192

193 194

195

Z . C. Profous, K. P. Wanczek, and H. Hartmann, 2.Naturforsch., 1975, 30a, 1470. C. Alvarez, A. Cabera, E. Cortes, and L. J. Gomez, Rev. Latinoamer. Quim., 1973, 4, 197 (Chem. A h . , 1974, 80, 101 431). Yu. Ya. Efremov, R. Z . Musin, N. A. Makarova, and E. T. Mukmenev, Khint. gcterotsikl. Soedinenii, 1974, 12, 1620. G. Cauquis, B. Divisia, and J. Ulrich, Org. Mass Spectrometry, 1975, 10, 770.

272

Organophosphorus Chemistry

two such phosphine sulphide groups are linked by a methylene chain or ethene group, as in (160), the phenyl groups migrate from one phosphorus atom to the other or to l ~ ~mass spectra of the the sulphur atom bound to the other phosphorus g r 0 ~ p . The difluorides (161) also provide evidence for the migration of aryl groups, in this case to the oxygen atom. Fragmentations involving loss of carbon monoxide (which are common with phenates) are detected, and therefore the molecular ion is assigned the three-co-ordinate structure (162).Ig7 A wide range of dioxaphosphorinans (163) has been studied. In all cases hydrogen migration from the cyclic alkyl residue is an important feature. Other fragmentations are the result of simple bond fission. Deuteriation shows that the loss of methyl comes entirely from the geminal groups at C-5. The ionization potentials are lowest when a phenyl group is present, i.e. (163; Y = Ph, OPh, or CH,Ph), which is attributed to the removal of an electron from the aryl ring rather than from the usual ester oxygen atom. There is another exception when Y is a dirnethylamino-gr~up.~~~ A range of alkylphosphonic acids (164) which possess hydrogen at the 8-position of the alkyl group eliminate a methyl group or hydrogen to give daughter ions which fragment with loss of water. The methyl and bromomethyl acids (164; R = Me or CH,Br) fragment with immediate loss of water.lggThe mass spectra of a range of

Y

/

phosphorylated derivatives of phenols have also been reported.200Combined gas chromatography and mass spectrometry has been used to analyse the acetolysis products of phosphatidylcholine201and for the determination of l 6 0 to l8O ratios in inorganic phosphates after their conversion into tributyl phosphate.202The g.1.c.mass spectral identification of steroids uiu the dimethylphosphinic esters and the corresponding thiophosphinic esters has been investigated.203 10 pKa and Thermochemical Studies A comparison of the basicities of Group VA element organic derivatives in nitromethane solution showed that trioctylphosphine oxide (165; R = octyl) is a much weaker base than the corresponding amine oxide or hexamethylphosphoric triamide.

l g 6G.

197 198 199

200 201 202

c03

Cauquis, B. Divisia, and J. Ulrich, Org. Mass Spectrometry, 1975, 10, 1021. L. W. Daasch and R. W. Gamache, Phosphorus, 1975,5, 189. G. W. Francis, K. Tjessem, A. Dale, and T. Granstad, Acta C h m . Scand. ( B ) , 1976, 30, 31. W. R. Griffiths and J. C. Tebby, Phosphorus, 1975,5, 273. R. J. Cremlyn and N. Kishore, Phosphorus, 1974, 5, 47. K. Hasegawa and T. Suzuki,Lipids, 1975, 10, 667. D. Barltrop and P. A. Lewis, Analyst, 1975, 100, 862. K. Jacob, W. Schaefer, W. Vogt, and M. Knedel, 2. analyt. Chem., 1976, 279, 163.

Physical Methods

273 0

This is attributed to p,,-d, back-bonding in (165).204A comparison of acidity of the phosphine oxides such as (166) with the sulphides showed that the oxides are far more sensitive to changes in the media, and their pKa’s in diglyme are three to five orders of magnitude higher than they are in DMSO. The comparisons were made by transmetallation relative to the indicator-acid f l u ~ r e n eThe . ~ ~study ~ has been extended to substituted benzylphosphine oxides (167), and it was concluded that the sensitivity of the oxides to changes in the media is due to co-ordination of the cation to the phosphoryl group.2osMeasurement of the base-catalysed deuterium exchange of the a-protons in a series of phosphine oxides, phosphine sulphides, and phosphonium salts showed that their acidities increase in the order given, and that the acidities of the trialkylphosphineoxides increased with shortening of the alkyl chain.2o7The pKa values of the hexamethylenediamine derivatives (168) 208 and the methylenediphosphonic acids (169) 209 have been measured, and Hammett-Taft correlations made in the latter work. The standard enthalpies of combustion and formation of crystalline phosphonic and phosphinic acids (170), (171), and (172) have been determined.210 The reactions of a variety of PI11 chloro-compounds (173; X and Y = Cl, OEt, Et, or Ph) with acetal to give PI11 esters (174) have been followed by thermogravimetry.211

204 205

206 207

208

210

211

B. N. Laskorin, V. V. Yakshin, and L. I. Sokal’skaya, Doklady Akad. Nauk. S.S.S.R., 1975, 223, 1405. S. P. Mesyats, E. N. Tsvetkov, E. S. Petrov, M. I. Terekhova, A. I. Shatenshtein, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1974, 23, 2399. S. P. Mesyats, E. N. Tsvetkov, E. A. Petrov, N. N. Shelganovo, T. M. Shcherbina, A. 1. Shatenshtein, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R., 1974, 23, 2406. N. N. Zatsepina, I. F. Tupitsyn, and A. I. Belashova, Reakts. Sposobn. Org. Soedinenii, 1974, 11,431 ;N. N. Zatsepina, I. F. Tupitsyn, B. B. Alipov, A. Belashova, A. V. Kirova, and N. S. Kolodina, ibid, p. 445. B. V. Zhadanov, I. A. Polyakova, S. P. Ivashchenko, V. Ya. Temkina, and R. P. Lastovzkii, Zhur. fiz. Khim., 1975,49, 3009. L. Maijs and 0. Lukevic, Latv. P.S.R. Zinat. Akad. Vestis, Kim. Ser., 1975, 4, 473. A. Finch, P. J. Gardner, K. S. Hussain, and R. A. Melaugh, J. Chem. Thermodynamics, 1975, 7, 881. M. B. Gazizov, D. B. Sultanova, A. I. Razumov, T. V. Zykova, N. A. Anoshina, and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.), 1975, 45, 1670.

274

Organophosphorus Chemistry

11 Chromatography and Surface Properties G.1.c.-May be used for the analysis of pesticide residues,212phosphates in water,212 phosphamide in milk and 214 and phosphatidyl~holines.~~~ T.1.c.-A modified Jungnickel's reagent has been used for detecting phospholipids 216 and other phosphorus compounds, and pyridine-4-aldehyde-2-benzothiazolylhydrazone (PBH) is recommended for the quantitative determination of cyclophos. ~ ~ ~chromatographic behaviour of phamide (17 9 , ifosfamide, and t r o f o ~ f a m i d eThe 0

(175)

phosphatidylserine and phosphatidic acid has been studied.218Low temperatures (- 70 "C)are recommendedfor theseparation of phosphoglycerides,according to the number and length of the saturated fatty-acid components.21sAnion-exchange t .l.c. separates p-nitrophenyl phosphate, ATP, and inorganic phosphate.22* Paper Chromatography.-A ketonic solvent system has been recommended for the rapid determination of nucleotide-inorganic phosphate mixtures,221and a procedure for the simultaneous determination of metabolites of various chemical classes has been developed.222 Column Chromatography.-High-performance liquid chromatography provides a sensitive analysis of ethanolamine- and serine-containing phosph~glycerides.~~~ Flavine phosphates have been Oligomers of deoxyadenylic acid covalently attached to poly(viny1 alcohol) are strongly adsorbed on DEAE-cellulose and may be used for the separation of deoxythymidylicacid 01igomers.~~~ Anion-exchange high-pressure liquid chromatography provides an excellent method for the determination of adenosine phosphates.226Nucleotide phosphates have been concentrated by ion-exchange ~ h r o m a t o g r a p h y . ~ ~ ~ M. A. Luke, J. E. Froberg, and H. T. Masumoto, J. Assoc. Ofic.Analyt. Chemists, 1975,58, 1020; Y . Aoki, M. Takeda, and M. Uchiyama, ibid., p. 1286. 213 D. A. J. Murray, J . Fish. Res. Board, Canada, 1975, 32, 457. 214 V. V. Leshchev and T. G. Abbasov, Khim. SeI'sk. Khoz., 1975,13,616 (Chem. Abs., 1975,83, 191 430). 215 J. F. Soodsma, L. C. Mims, and R. D. Harlow, Biochim. Biophys. Acta, 1976,424, 159. 216 V. E. Vaskovskii and N. A. Latyshev, J. Chromatog., 1975, 115, 246. 217 K. Norpoth, H. W. Addicks, U. Witting, G. Mueller, and H. Raidt, Arzneim.-Forsch., 1975, 25, 1331. 218 H. Nielsen, J. Chromatog., 1975, 114, 419. 219 R. F. Henderson and M. H. Clayton, Ann. Report Inhalation Toxicol. Res. Inst., 1974, 220. 220 A. S. Hobbs, Analyt. Biochem., 1975, 66, 620. Zz1 J. Heinonen, Finn. Chem. Letters, 1975, 105. 222 N. G. Doman, Metody Sovrem. Biokhim., 1975, 48. 223 F. B. Jungalwala and R. J. Turel, Biochem. J., 1975, 145, 517. 224 P. Betto, R. Gabriele, F. Mazzaracchio, and L. Longinotti, Ann. Ist. Super. Sanita, 1974, 10, 240. 225 H. Schott, J . Chromatog., 1975, 115, 461. 226 S. H. Tsung, T. Y . Wang, E. A. Sasse, and J. V. Stanmfjord, Ann. Clin. Lab. Sci., 1976,6, 193. 227 A. I. Voskoboev, I. P. Chernikevich, and V. V. Grushnik, Vestsi Akad. Navuk B. S.S.R., Ser. Biyal. Navuk, 1975,5, 114 (Chem. Abs., 1976, 84, 1870).

212

Physical Methods

275

The surface tensions of some fatty-acid phosphates have been determined 228 and the surfactant properties of perfluoroalkanesulphonamidoalkanephosphonicacid and corresponding phosphinic acid derivatives

228 229

M. Nakagaki and T.Handa, Bull. Chem. SOC.Japan, 1975,48, 630. R. Schliebs, M. Wechsberg, and J. N. Meussdoerffer, Ger. Offen, 2424243 ,1974 (Chem. Abs., 1976,84, 59 747).

Author Index Abalonin, B. E., 80 Abbas, K., 130 Abbasov, T. G., 274 Abdallah. M. A.. 134 Abdel-Rahman, M.O., 113 Abdulla, K. A., 2 Abduvakhabov, A. A., 251 Abel, E. W., 20 Abeles, R. H., 135 Abraham, K. M., 53, 253, 256 Abramov, V. N., 89 Abramowitz, S., 62 Abul'kanov, A. G., 84 Achremowicz, L., 128 Adams, M. J., 134 Addicks, H. W., 274 Adolphi, H., 227 Agarwal, K. L., 169,171,173 Agarwal, S. C., 240 Aguiar, A. M., 3 Ahlers, J., 144 Ahmed, F. R., 227 Ahmed, S., 67 Aida, T., 16 Ailman, D. E., 102 Akasawa, T., 230 Akhmedov, Sh. T., 66 Akiba, K., 76 Aksnes, G., 22 Akutsu, H., 266 Albanbauer. J.. 45. 88 Albano, V. G.,'230 Albrecht, H. P., 195 Albright, T. A., 82, 179,250, 253

Al'fonsov, V. A., 209, 217 Alipov, B. B., 273 Alkaysi, H. M., 66 Allcock, H. R., 223, 225, 227, 228 Allen, L. B., 153 Allen, N. P., 2 Alley, W. D., 94 Allison, W. S., 134 Alscher, D., 81 Althoff, W., 64 Altmann, J. A., 33 Alvarez, C., 271 Aly, H. A. E., 32 Amarnath, V., 153 Amarskii, E. G., 82 Amato, B. A., 119, 149 Ames, B. N., 163 Aminova, R. M., 255,258 Ammon, H. L.. 11 Amornraksa, K.,28 Amos, J., 122 Amsler. P. E.. 164 Andersen, J. R.,247 Anderson, A. J., 141 Andersson, L., 160

Anderson, R. J., 193 Anderson, S. P., 249 Andreev, G. F., 75, 90 Andreev, N. A., 110, 11 1 Andreeva, M. A., 224 Andreo, C. S., 144 Andrews, A. G., 197 Andrianov, V. G., 132, 267 Anh, N. T., 60 Anker, W. M., 230 Ankilova, V. N., 165 Anoshina, N. A., 57, 273 Anoshina, N. P., 38, 54, 95 Anteunis, M., 179 Antowiak, A., 228 Anwar, R. A., 140 Aoki, Y., 274 Aoyama, H., 219 Appel, R., 3, 12, 13, 14, 34, 41, 51, 58, 68, 69, 70, 93, 177, 211, 214, 216, 218 Appelbaum, J., 140 Arase, Y., 183 Arbuzov, B. A,, 39, 44, 54, 57, 86, 88, 92, 95, 124, 126,131,254,255,259,270 Archibald, A. R., 141 Arcoria, A., 90 Arkhipova, G. G., 227 Armitage, I. M., 144 Armour, M.-A., 242 Armstrong, V. W., 166 Arnold, Z., 108 Arrington, D. E., 92, 208, 217 Arsent'eva, T. V., 80 Arshinova, R. P., 131, 259, 270 Artz, S. W., 163 Asahara, T., 183 Asaoka, M., 124 Ashani, Y., 146 Ashe, A. J., 29, 269 Ashkinazi, L. A., 270 Aslanov, Kh. A., 251 Asscher, H., 239 Astone, F., 124 Athawale, B. K., 122 Atkinson, A., 134 Audette, R. J., 147 Autzen, H., 95, 207 Aviv, H., 175 Azerbaev, I. N., 5 Azhaev, A. V., 154, 248 Aziz, A. R., 205 Babiarz, P. S., 147 Babkina, E. I., 59 Baccolini, G., 7, 128 Baddiley, J., 141 Radran, A. H., 2 Baer, F., 240

276

Baes, M., 20, 199 Bauerlein, E., 143, 144 Baumer, G., 13 Baglioni, C., 174 Bagri, E. I., 102 Bagrov, F. V., 127, 204 Bagshaw, C. R., 162 Bahl, C. P.. 169

Baker, D. C . , 1'5 Bakulin, V. S., 118 Bakulina, G. V., 265 Balakrishnan, V., 180 Bamgboye, T. T., 230 Banaszek, A,, 15 Banks, C. H., 186 BirAny, M., 176 Barbalat-Rey, F., 196 Barlow, J. H., 32 Barlow, L., 196 Barltrop, D., 272 Barneis, Z., 15 Barrans, J., 31, 97, 252, 264 Barrell, B. G., 173 Bartczak, T. J., 98, 13 1 , 250 Bartell, L. S., 5 1 Barth, R. C., 2 Barthelat, M., 264 Bartholomew, D. G., 153 Barton, D. H. R., 17, 244 B%rzu, O., 162 Basha, A., 67 Bashirova, L. A., 66 Basset, J., 2 Bassler, H. J., 251 Bates, G. S., 181 Batrakov, S. G., 266 Baturina, L. S., 221 Batyeva, E. S., 86, 209, 217 Bauer, G., 207, 254 Bauld, N. L., 240 Baumer, G., 69 Bayer, E., 2 Bearder, J. R., 182 Beasley, G. H., 199 Beaucage, S. L., 170 Becher, H. J., 3, 8, 60 Bechgaard, K., 247 Beck, H. C., 258 Becker, E. D., 249 Becker, G., 3, 59 Bee, L. K., 187 Beeby, J., 187 Beg, M. A. A., 242 Begley, M. J., 230 Belashova, A. I., 273 Belitsina, N. V 175 Bell, W. J., 193" Belov, V. A., 227

277

Author Index Belov, Yu. P., 266 Bel'skii, V. E., 251,264 Belyaev, Yu. P., 221 Benary, E., 6 Benatti, V., 160 Benezra, C., 129,253 Benisek, W. F., 147 Benkovic, S. J., 119, 149 Bennett. G. N.. 172 Bennett; M. A.; 1 Bentrude, W. G., 98,235,252 Berbeco, G. R., 230 Berchtold, G. A., 240 Berclaz, T., 261 Berdnikov. E. A.., 256 Berg, C., 247 Bergel'son, L. D., 266 Berger, H. O., 5 Berlin, K. D., 18, 19, 22, 73, 110,252, 267 Berlin, Y. A., 169 Berliner, L. J., 139, 160 Berman, S. T., 20 Bernard, D., 39 Bernardi, F., 251 Bernot, K. G., 74 Bernstein, L. S., 62 Bertazzoni, U., 174 Bertina, L. E., 71 Bertinchamps, A., 262 Besmer, P., 171 Bespal'ko, G. K., 123 Bestman, H. J., 177, 178, 180, 186, 189, 190, 193, 241, 267 Betto, P., 274 Bhacca, N. S., 3, 139, 240 Bhatawdekar, S. S., 119 Bhattacharyya, P. K., 255 Bianchini, J.-P., 85 Bickelhaupt, F., 29, 30, 260 Biddlestone, M., 54, 215, 223,230 Biellmann, J. F., 134 Billiau, A., 172 Bindra, J. S., 202 Bisagni, E., 200 Bitter, W., 86, 214 Bittner, S., 15 Black, W. H., 147 Blakely, R. L., 160 Blanchard, J., 142, 201 Blasie, J. K., 248 Block, J. L., 144 Blumenfeld, J., 17 Blumenstein. M.. 135 Boate, A. R;,237 Bobek, M., 19 Bock, H., 204, 266 Bodalski. R.. 73 Bode, J.,' 176 Boden, R. M., 179 Bodnarchuk, N. D., 66, 212 Boehme, R., 267 Boggess, R. K., 1 Boigegrain, R., 13, 37, 93 Boianovski. D.. 162 Bokanov, A. I.; 1 Bokij, N. G., 131, 268 Boldesskul, I. E., 93, 208 Bollinger. P.. 194 BondGenko,'V. A., 131 Bone, S. A., 91 BOOS,K.-S., 162 ~~

Borisenko, A. A,, 259 Borisov, A. Y., 154 Borisov, E. V., 265 Borisov, G., 83 Borisova, E. E., 45, 86 Borleske, S. G., 251 Borovikov, Yu. Ya., 83, 262, 270 Borri-Valtattorni, C., 136 Boswell, K. H., 159 Bosyakov, Y. G., 5 Both, G. W., 174 Bottcher, W., 255 Botteghi, C., 17 Boucher, L. J., 5 Boudreau, J. A., 117 Boudreaux. G. J.. 79. 100 Bowers, L.'D., 133 . Boyer, H. W., 174 Boyer, P. D., 143, 162 Bradley, J. C., 199 Bradv. J. T.. 167 Brand; W., 77 Brandsma, L., 80 Brandt, K., 228 Brantham, G. D., 199 Braun, R. W., 34 Bravo, P., 188 Braxton, H. G., 229 Breen, J. J., 252 Brehme, H., 162 Breitmaier, E., 207, 254 Brennecke, L., 114 Breuer, E., 202 Briggs, E. M., 219 Brightwell, N. E., 240 Broadhurst, M. D., 199 Broch, G., 197 Brodelius, P., 160 Brooks, R. J., 130 Broom, A. D., 153, 172 Broos, R., 179 Brown, C., 117 Brown, D. H., 236 Brown, G. W., 219 Brown, J. M., 199 Bruin, J. W., 202 Bruns, R. E., 269 Bruns, W., 164 Brunton, G., 238, 261 Bruzik, K., 119 Brynolf, K., 175 Buchanan, G. W., 253 Buchecker, R., 197 Buchholtz, N., 228 Buchi, G., 199 Buchikhin, E. P., 82 Buchner, M., 134 Buck, H. M., 238 Buckler, S. A., 100 Bodalski, R., 87 Buder, W., 208, 219, 262 Biichi, H., 171 Bugerenko, E. F., 265 Bula, M. J., 253 Bunton, C. A., 130 Buono, G., 39 Burd, J. F., 173 Burgada, R., 38, 39, 259 Burger K., 45, 88,210 Burge;, P. M. J., 155, 156, 170 Burghoff, U., 256 Burgis, E., 45, 88

Burgstahler, A. W., 193 Burks, J. E., 82 Burnaeva, L. A., 90, 107 Burnett, R. E., 3 Burns, F. B., 21, 266 Burns, R. P., 2 Burt, C. T., 176 Burton, D. J., 66,68,177,186 Burzlaff, H., 267 Busby, S. J. W.,133, 137,164 Buschek, J., 147 Busulini, L., 227, 228 Butin, B. M., 5 Butler, L. G., 110, 144, 252 Butorin, A. S., 175 Bykhovskaya, E. G., 124,125 Bykov, V. A., 230 Bykova, I. V.,270 Cabera, A., 271 Cadogan, J. I. G., 32,42,43, 242,243,244,253,268 Cain, J. E., 248 Calderon J., 105 Calhoun, H. P., 231 Cameron, T. S., 82, 222, 230,266,268 Cammack, K. L., 84, 200 Camps, F., 203 Canaani, D., 174 Carlson, J. P., 148 Carman, R. M., 66 Carr, P. W., 133 Caruthers, M. H., 171 Cary, L. W., 139 Cashel, M., 163 Cashion, P. J., 171 Castro, B., 13, 37, 93 Caughlan, C. N., 21,266,268 Caulton, K. G., 256 Cauquis, G., 271, 272 Cava, M. P., 247 Cavell, R. G., 34,50,255,269 Cederbaum, L. S., 27 Centofanti, L. F., 51 Ceriotti, A., 230 Cermak, J., 229 Chabrier, P., 104, 127 Chaby, R., 138 Chaconas, G., 174 Chadaeva, N. A., 80 Chaiken, I. M., 160 Chalykh, E. A., 83 Chalykh, S. N., 83 Chambers, J. Q . , 247 Chan, D. M. T., 23 Chan, T. H., 74,233 Chan, W.-T., 29, 269 Chandrasekhar, K., 134 Chaplew, Y., 13 Charbonnel, Y., 264 Chaser, D. W., 242 Chattopadhyaya, J. B., 122 Chaudri, T. A., 205 Chaus, M. P., 57, 121 Chauzov, V. A., 71 Chawla, 0. P., 238 Chekhun, A. L., 88 Chelsky, D., 146 Cherepinskii-Malov, V. D., 267 Cherkasov, R. A., 270 Chernikevich, I. P., 274 Chernova, A. V., 263

Author Index

278 Chernyshev, E. A., 265 Chernyuk, I. N., 19 Chesnut, R. W., 267 Chinault, A. C., 161 Chini, P., 230 Chirgwin, J. M., 144 Chistokletov, V. N., 54 Chittenden, R. A., 104, 122 Chlebowski, J. F., 144 Chow, K. K., 3 Christ, W., 134 Christau, H. C., 23 Christe, K. O., 70 Christensen, A., 98, 131, 250 Christol, H., 23 Chukbar, T. G., 86 Chung, L.-L., 233 Church, R. B., 174 Chuvylkin, N. D., 258 Ciani, G., 230 Cihak, A., 148 Cinouini, M., 27 Ciubotariu, D., 224 Claisen, L., 66 Clapp, C. H., 122 Clardy, J. C., 33, 85 Clari, G., 147 Clark, C., 239, 262 Clark, H. C., 70 Clark, P. W., 1, 9 Clark, R. D., 201 Claxton, T. A,, 234 Clayton, M. H., 274 Clement, B. A., 177 Clements, A. C., 130 Clint, J. H., 83 Cloyd, J. C., jun., 5 Clutter, R. J., 229 Cobianchi, L., 165 Coffey, P., 50 Cohen, E. A., 206 Cohen, H., 129 Cohen, H. I., 13 Coleman, J. E., 144 Coll, J., 203 Collignon, N., 142, 201 Colman, A., 249 Colonna, S., 27 Colussi, A. J., 237, 262 Coman, R. E., 196 Comer, M. J., 134 Conesa, A. P., 221 Connelly, T. M., 228 Contreras, R., 173 Cook, A. F., 162 Cook, P. D., 153 Cook, R. D., 130 Cook, W. J., 228 Cooper, D. B., 103 Cooper, G. H., 122 Cooper, J. W., 235 Cooper, P., 11 Cooperman, B. S., 144 Corbel, B., 123 Corev. E. J.. 148 Corei; R. M.,23 Cornus, M., 259 Corrie, J. E. T., 242 Cortes, E., 271 Cortez, C., 10 Cosgrove, D. J., 141 Costa, D. J., 65 Costello, A. J. R., 141, 249, 254

Costisella, B., 114 Cottet, C., 196 Coult, D. B., 146 Coultas, C., 176 Couret. C.. 18. 60. 61 Couret; F.; 61' ' Coutrot, P., 200 Cowley, A. H., 34, 50, 64, 206 Cox, A. W. jun., 263, 264 Cox, P. J., 108 Cramer, F., 158, 161 Craven, D. B., 134 Crea, R., 160, 170 Creese, M. W., 66 Cremlyn, R. J., 259, 272 Cross, R. J., 236 Csavhssy, G., 210 Csizmadia, I. G., 33 Cullis, P. R., 133, 142, 248, 249 Curtis, E. C., 70 Cuvigny, T., 124 Czuba, L. J., 194 Daasch, L. W., 272 Dahl, O., 6, 258 Dahlen, B., 82, 266 Daigle, D. J., 8 Dailey, B. P., 255 Dale A 272 Dalgieisg, W. H., 21 3, 220 Dalla Croce, P., 191, 192 Damadian, R., 249 Dandarova, M., 201 Danel, J., 82 Danilov, L. L., 137 Dansette, P., 240 Dhsoreanu. M.. 162 Darling, S. D., 126, 127 Das, K., 134 Dauben, W. G., 26, 190, 199 Davankov, V. A., 266 David, J., 259 Davidek, J., 270 Davidson, A. H., 79 Davletshina, Kh. Kh., 263 Dawber, J. G., 22, 186 Dawson, W. T., 219 Dea, P., 153 Dean, P. D. G., 134 D$:$, N. J., 35, 56, 63, 76, LJJ

de Boer, J. J. J., 181 De Bruin, K. E., 27, 131 de Clercq, E., 172 de Crombrugghe, B., 174 de Flora. A.. 160 Degani, C., 143 Deighton, M., 182 De Ketelaere, R. F., 82 de Koning, H., 202 de Kruijff, B., 133, 142 De Kruyff, B., 249 Delmar, E. G., 2 Demarcq M., 75 De Moss: R. D., 135 Dempsey, A. M., 67 den Hartog, J., 155 Denney, D. B., 35, 63, 255 Denney, D. Z., 35, 63, 255 Depew C., 15 Derby,'E., 220, 225 Derkach, G. I., 81, 208

ie Rooy, J. F. M., 156 Descotes, G., 2 ie Somer, P., 172 Devillers, J., 259 Devoe, S. V., 253 3ewar, M. J. S., 50 Dianova, E. N., 88,92 Dichtelmuller, H., 163 Xeck, H., 50, 266 Diercksen, G. H. F., 27 Dilbeck, G. A., 19 Dillon, K. B., 259 Dimroth, K., 30,80,239,240 Disteldorf, W., 71, 128 Distler, W., 186, 241 Divisia, B., 271, 272 Dixon, H. B. F., 138 Doak, G. O., 34 Dobbie, R. C., 52 Dodgson, J. B., 173 Dodonov, A. M., 52 Doebhakta, S., 119 Doi, K., 229 . Dolgushina, I. Y., 19, 84 Doman, N. G., 274 Dombrovskii, A. V., 23 Dombrovskii, V. A,, 21, 75, 180 Donaubauer, A., 5 Donella, A., 147 Donelson, J. E., 173 Donskaya, Yu. A., 263 Dorokhova, N. I., 218 Doroshenko, V. V., 81, 208 Dorozhkina, G. M., 263 Dorset, D. L., 269 Douglas, K. T., 131 Dowhan, W., 141 Downie, I. M., 26 Drabarek, S., 1 Drach, B. S., 19, 67, 84 Dreher H., 77 Dreux,'M., 122, 123, 200 Dubinina, T. N., 102 Dubois, D. L., 5 Duerinck, F., 173 Dumas, L. B., 172 Dumm, H. V., 41, 64 du Mont. W.-W., 12, 59 Duncan, 'L. A., 122 Dunnill, P., 134 Durham, N. N., 267 Durig, J. R., 51, 262, 263, 264 Dustmukhamedov, T. T., 97 Dutasta, J. P., 51, 257 Dwyer, J., 2 Dyrenko, L. V., 207 Dziedzic-Goclawska, A., 262 Ealick, S. E., 82 Easterbrook-Smith, S. B., 133 166 Ebert,' H. D., 17, 76 Eckstein, F., 160, 161, 164, 166, 172 Edwards, R. G., 142 Efremov, Yu. Ya., 271 Egorov, Yu. P., 62, 83, 219, 262, 270 Eidem, A., 197 Eigel, A,, 160 Eiletz, H., 227 Einhellig, K., 45

279

Author Index Einig, H., 70 Elbel, S., 50 El-Dmk. M.. 22. 73 Eliseenkova,’R. ’M., 56 Eliseeva, G. I., 139 Eliu-Ceasescu, V., 221 Elizarov, S. M., 175 Ellis, P. D., 256 Elson, I. H., 236 Emsley, J., 52 Emul, R., 60 Ene, D., 221 Engel, J., 162 Engelhardt, U., 267 England, T. E., 169 Engler, E. M., 247 English, A. D., 254 Enoki, Y.,16, 152, 245 Entwistle, D. W., 170 Erbland, M. L., 51 Ernst, L., 158, 248 Erokhina, T. S., 71 Err, E. A., 112 Escudie, J., 18, 60, 61 Esparza, F., 249 Evans, A. G., 234,260 Evans, F. E., 249 Evans, J. C., 234, 260 Everett, J. W., 187 Everse, J., 134 Evstigneeva, R. P., 137, 266 Evteev, A. M., 221 Ewig, C. S., 50 Ezra, F. S. 261 Fafikov, S. R., 59 Failor, R., 239, 262 Falardeau, E. R., 34, 52 Farmer, P. B., 108 Fattakhov, S. G., 52 Federov, S. G., 221 Fedin, E. I., 255, 259 Fedorova, G. K., 111 Fedyuk, G. S., 102 Fehrle, M., 95 Felcht, U., 91 Feldman, R. J., 176 Felix, S., 15 Fenske, D., 3, 8, 60, 266 Feshchenko, N. G., 51, 57 Fessenden, R. W., 238, 262 Fjadaca, P., 186 Field, L., 186 Fields, E. K., 71 Fields. R.. 11 Fiers, ‘W.,’ 173 Fikus, M., 172 Fild, M., 32, 64, 206, 257 Filippov, E. I., 227, 229 Finch. A.. 62.273 Findlay, J. A:, 193 Findlay, R. H., 27 Finnegan, R. A., 233 Finnik, V. P., 86, 209 Fisher, J., 135 Fishman, A. I., 51 Fisichella, S., 90 Fiszer, B., 108 Fitzgerald, A., 21, 266 Flavell, R. A., 175 Flick, W., 100, 214 Flitsch, V. W., 24 Flitsch, W., 183

Florent’ev, V. L., 154., 157, 171, 248 Fluck, E., 8, 66, 219, 220 Foerster, J. E., 8 Fondy, T. P., 147 Fookes, C. J. R., 99, 233 Ford, G. C., 134 Ford, M. E., 246 Foster. C. H.. 240 Foucaud, A.,’46, 93 Fountaine, J. E., 11 Francis, G. W., 272 Frank, V., 230 Fraser, T. H., 153 Frazier, J., 153, 172 Freedman, H. H., 118 Freeman, W. J., 82, 253 Freijee, F. J. M., 29 Freist, W., 161 Fridkin, M., 171 Fridland, S. V., 52 Friedrich, K., 179 Fritz, G., 59, 60 Fritz, H.-J., 169 Froberg, J. E., 274 Fry, A. J., 233 Frydman, V. M., 182 Frye, R. B., 153 Fiirst, M., 147 Fuertes, M., 153 Fujimoto, Y., 244 Fukazawa, A., 188 Fukuda, K., 266 Fukuda, M., 86 Fukuhara, M., 230 Fukui, S., 137 Fukui, T., 153, 172 Fullam, B. W., 51, 234, 236 Fuller, H. J., 184 Furuichi, Y.,174 Furukawa, N., 16 Fuzhenkova, A. V., 88 Fyles, T. M., 239 Gabriele, R., 274 Gadian, D. G., 137, 249 Gaidamaka, S. N., 34, 70, 205. 213 Gait, ’M. J., 169 Gakis, N., 125 Galaktionova, 0. V., 254 Galishev, V. A., 54 Gallagher, M., 39, 49, 118 Gallagher, M. J., 7, 99, 100, 233 Gallaher, K. L., 240 Gallo, A. A., 137 Gally, H. U., 142 Galunski, B., 202 Gamache, R. W., 272 Ganba, A. L., 203 Gara, W. B., 238 Gardner, B. C., 229 Gardner, J. E., 227 Gardner, P. J., 62, 273 Gareev, R. D., 45, 86, 92, 129, 210, 217 Garfin, D. E., 174 Garito, A. F., 247 Garratt, P. J., 187 Garrett, P., 104 Gaskin, P., 182 Gassen, H. G., 153 Gasser, O., 178

Gates, P. N., 62 Gatilof, Y.F., 80 Gavdou. E. M.. 85 Gaiizov; M. B.; 57, 273 Gazizov, T. Kh., 54 Geanangel, R. A., 263 Gehlert, P., 222 Geisler, K., 3 Gelbard, G., 17 Gence, G., 39, 48, 118, 252 Gennaro, G. P., 240 Geoffroy, M.. 261 Georghiou, P. E., 181 Gerard, G. F., 172 Gerber, A. H., 227 Geresh, S., 17 Gerlt, J. A., 139 Germa, H., 38 Gernayova, M., 201 Gesing, E. R., 24 Ghisla, S., 135 Ghkata, K., 58 Giartosio, A., 136 Gibson, D. M., 10, 89 Gibson, J. A., 34,49,58,206 Giesen, K., 13 Gifkins, M. R., 267 Gilak, A., 34, 58 Gilbert, B. C., 238 Gilham, P. T., 172 Gilje, J. W., 34 Gillen, R. C., 159 Gillespie, D. G., 4 Gillham, J. K., 228 Gilligan, T. J., 266 Gil’man, L. M., 224 Gilyarov, V. A., 207 Gilyazov, M. M., 52, 59 Giniyatullin, R. S., 54 GirbCs, T., 164 Girfanova, Yu. N., 86, 209 Gitel’, P. O., 224 Giuliano, F., 160 Glaebel, W., 96 Glaser, R., 17 Glaser, S. L., 259, 268 Glassel W., 208 Glidewkll, C., 122, 204, 213, 217 Glinskii. Yu.D., 112 Gloede,’J., 46 . Glonek, T., 111, I 41Y 176, 249,254 Gloyna, D., 74 Glukhikh, V. I., 20, 131 254 Glukhova, M. A., 175 Gnauk, T., 114 Goda, K., 76 Godovikov, N. N., 251 Goerdeler, J., 17 Goetz. H.. 81 Goia,I., 162 Golas, T., 172 Gold, M. H., 141 Gol’dfarb, E. I., 57, 76, 126 Gol’din. G. S.. 221 Goldman, J., 124 Goldsmith, B., 124 Goldstein, J. H., 255 Goldwhite, H., 249 Gololobov, Yu. G., 93, 113, 121,208,211 Gomez, L. J., 271 Gomm, M., 267

Author Index

280 Goodgame, D. M. L., 268 Goodman, D. W., 50 Goodman, H. M., 174 Goody, R. S., 161 Gorbatenko, Zh. K., 51 Gordon, M. D., 250 Gorenstein, D. G., 117, 176 Gorlov, Yu. I., 261 Gosling, P. D., 52 Gosman, I. P., 84 Goto, Y., 230 Gottikh, B. P., 154, 248 Gould, R. O., 32, 242, 244, 268 Gould, S. E. B., 32,242, 268 Goumet, M., 160 Grace, D. S. B., 42, 43, 242, 253 Grachev, S. A., 119 Grade, R., 163 Graham, T. L., 139 Grande, H. J., 137 Granoth, I., 78 Granstad, T., 272 Grapov, A. F., 104, 107, 110, 124 Gray, D. M., 172 Gray, G. M., 2 Gray, M. W., 158 Grayson, M., 245 Grechkin, E. F., 65, 109 Green, D. C., 247 Green, M., 172 Greene, G. L., 169 Greengard, P., 139, 165 Greenside, H. S., 118 Gregoli, S.,262 Grewal, M. S., 203 Grieco, P. A., 194 Griffin, G. W., 10, 89, 240 Griffin, R. G., 142 Grlffing, M. E., 229 Griffith, E. J., 245 Griffiths, G. R., 149 Griffiths, W. R., 272 Griller, D., 239 Grim, S. O., 2, 16, 79 Grinblat, M. P., 224 Gringauz, A., 84 Grishina, 0. N., 110, 111 Grobe, J., 33, 62, 269 Grohman, K. G., 199 Groner, Y., 174 Gross, B., 13, 93 Gross, H., 46, 90, 114 Gruber, L., 12, 68 Gruenwedel, D. W., 175 Grunberger, D., 176 Grushnik, V. V., 274 Grzejszczak, S.,201 Guenther, O., 128 Gueron, M., 249 Guillory, R. J., 165 Guimaraes, A. C., 99 Gunther. M.. 85 Gupta, K.C:, 203 Gurarii, L. I., 254 Gusar’, N. I., 57, 121 Guschlbauer, W., 151 Guseva, T. A., 86, 13 ,59 Gutfreund, H., 133 Gutowski, J. A., 137 Haake, P., 90, 110

Hackett, M. L., 134 Haegele, G., 55 Haegman, G., 173 Hagedorn, I., 180 Hagen, K., 269 Hagnauer, G. L., 204,228 Hahn, H. J., 141 Haitaka, T., 219 Haley, B. E., 133, 165 Halford, S. E., 133 Hall, C. D., 63 Hall, C. R., 103, 104 Hall, L. W., 256 Haller, R., 261 Halstenberg, M., 41,214,218 Hamacher, H., 109 Hamada, A., 11, 88 Hamada, M., 16,245 Hameed, A., 62 Hamel, E., 153, 164 Hampton, A., 153, 166 Handa, T., 275 Hands, A. R., 142 Hannon, S. J., 178 Hapke, B., 172 Hara, H., 137 Hara, K., 229 Hardcastle, K. I., 9 Hardy, D., 219 Harger, M. J. P., 130, 259 Hargis, J. H., 94 Harlow, R. D., 274 Harper, P. J., 166 Harris, R. K., 35,206, 257 Hart, D. J., 26, 190 Hartke, K., 128 Hartl, H., 267 Hartman, F. C., 147 Hartman, J. S., 253 Hartmann, H., 271 Harvey, M. J., 134 Harvey, R. G., 10 Haschke, J. M., 51 Hasegawa, K., 272 Haskell, T. H., 153 Hasova, B., 201 Hassairi, M., 46, 93 Haszczyc, B., 228 Haszeldine, R. N., 11 Hata, T., 92, 168 Hattori, M., 153, 172, 200 Hatzelmann, L., 45 Haubold. W.. 219 Hauser, A., 255 Havron, A., 165 Hawrelak, S. D., 153 Hav. J. V.. 187 Haiashi, M.,124, 194 Hayashi, T., 17 Hayes, F. N., 172 Heaney, H., 26 Heathcock, C. H., 201 Hecht, S. M., 153, 161 Hedberg, K., 269 Hedberg, L., 269 Heimer, E. P., 164 Heimgartner, H., 125 Heinonen, J., 274 Heitmann. P.. 162 Helland, C., 30 Hellwinkel, D., 36 Hemminga, M. A., 133, 164, 248 Henderson, R. F., 274

Henderson, T. O., 249 Henning, H. G., 74 Henrick, C. A., 193 Hensel, W., 134 Hercouet, A., 190 Herman, M. A., 263 Herman, P., 270 Herrman, P., 124 Herrmann, E., 207, 254 Herrmann, K. M., 137 Herscovics, A., 141 Hersh, L. B., 135 Heskett, M. G., 175 Hess, H. J. E., 194, 202 Hestermann, K., 232 Heuschmann, M., 113 Heymann, M., 8, 60 Hickey, E. D., 174 Hideo, D., 233 Hieke, S., 261 Higashi, F., 99 Higgins, M. L., 267 Hillen, W., 153 Hino, T., 245 Hirabayashi, T., 141 Hirabayashi, Y., 76, 239 Hirth, C. G., 134 Hitchcock, P. B., 268 Ho, C., 249 Hoard, D. E., 172 Hobbs, A. S.,274 Hobbs, J., 164, 172 Hochleitner, R. H., 55, 76 Hodge, P., 14 Hoechst, A.-G., 177 Hogel, J., 227 Hohne, W. E., 162 Hoelderich, W., 3, 59 Hofer, H. W., 147 Hoffman, J. F., 133 Hoffman, P. R., 256 Hoffmann, P. J., 160 Hohler, W., 180 Holah, D. G., 29 Holbrook, S. R., 267 Holman, M. J., 162 Holmes, R. R., 33, 61, 62 Holroyd, R. A., 239, 262 Honjo, M., 158 Hook, E. O., 230 Horiguchi, M., 142 Horn. H.-G.. 204.228 Horner, L., 8 HorskB, K., 148 Houalla, D., 31, 41, 97, 252 Hough. L.. 67 Houghion,’ R. L., 137 Hoult, D. I., 133, 248 Howell, J. M., 33, 61 Howgate, P., 166 Hoyle, C. E., 232 Hozumi, T., 170 Hruska, F. H., 158 Hsu, Y.F., 35, 63, 255 Huang, C.-H., 142 Hudson, C. E., 240 Hudson, R. F., 98, 117, 250 Huffman, J. H., 153 Hughes, A. N., 27, 28, 29, 265 Hughes, C. R., 182 Huisman, H. O., 202 Hull, W. E., 133 Hussain, K. S., 273 ~

Author Index Hussey, H., 141 Hutchins, R. O., 95, 124 Hutchinson, D. W., 133 Huttner, G., 52 Hutton, W. C., 142 Hutzenlaub, W., 155, 156 Hyde, R. G., 270 Hynie, S., 157 Igi, K., 230 Iguchi, I., 99 Iguchi, Y., 194 Ikeda. S.. 137 Ikehaia, 'M., 168, 169, 171, 172 Ikeno, S., 229 Ikoto, N., 123 Il'yasov, A. V., 261 Imai, S., 58 Imaizumi, T., 175 Inamoto, N., 76, 234, 239, 25 1 Inch, T. D., 103, 104, 116 Indzhikyan, M. G., 23 Ingold, K. U., 239, 261 Inokawa, S., 20, 186 Ionin, B. I., 81, 88 Isaacs, N. S., 13 Iserentant, D., 173 Ishikawa, K., 10, 89, 240 Ishikawa, N., 92 Ishmaeva, E. A., 270 Ismailov, V. M., 66 Isobe, T., 260, 261 Isom, H. C., 135 Issleib, K., 88, 250, 255 Itakura, K., 169 Ito, M., 196 Ivancsics, C., 24, 25 Ivanov, B. E., 84, 118, 251, 264 Ivanova, N. A., 218 Ivanova, Zh. M., 113, 121 Ivanovskaya, K. I., 57 Ivanovskaya, K. M., 126 Ivantaeva, L. P., 270 Ivashchanko, S. P., 273 Izmailova, Z. M., 80 Iwaizumi, M., 260, 261 Jackson, A. H., 244 Jacob, K., 272 Jacobsen, C. S., 247 Jacobson, R. A., 267 Jaenicke, L., 149 Jahnke, P., 158, 168 Jamal, M., 262 James, B. R., 17 Jamieson, A. T., 175 Janik, B., 172 Janion, C., 153 Janssen, E., 22 1, 223 Janzen, A. F., 34 Jarolim, T., 3 Jarrell, H. C., 15 Jarvis, B. B., 11, 15 Jasinski, W., 105 Jastrow, H., 229 Jay, E., 171, 174 Jay, F. T., 176 Jeanloz, R. W., 141 Jebeleanu, G., 162 Jedlinski, Z., 228 Jeeves, I., 268

28 1 Jeng, S. J., 165 Jenik, R. A., 147 Jensen, F. K., 6, 258 Jerina, D. M., 240 Jesson, J. P., 254 Jirecny, J., 219 Johansen, J. E., 203 Johnson, D. M., 131 Johnson, M. R., 202 Johnson, P. W., 153 Johnston, D. N., 244 Johnston, R. B., 220 Jolly, J. G., 229 Jondorf, W. R., 138 Jones, D. S., 176 Jones, J. K. N., 15 Jones, R. R., 199 Jongsma, C., 29, 30 Jongsma, E. J., 260 Jorns, M. S., 135 Jornvall, H., 160 Joshi. B. S.. 180 Jubach, T.,'226 Jugelt, W., 128 Jungalwala, F. B., 274 Jurasek, A., 200 Kabachnik, M. I., 71, 82,83, 207, 255, 259, 273 Kagami, M., 143 Kagan, H., 17, 20 Kajiwara, M., 221, 225,227 229 Kakli, M. A., 2 Kalabina, A. V., 65, 109 Kal'chenko, V. I., 66, 212 Kaleja, R., 154 Kalinin, A. E., 132 Kaluzene, S., 226 Kalvoda, L., 148 Kamata, S., 188 Kanietani, T., 244 Kametani, Y., 229 Kan, K., 86 Kanamaru, H., 25 Kanazawa, H., 192 Kanska, M., 1 Kao, J. T. F., 224, 229 Kaplan, N. O., 134 Kappler, F., 153 Kar, D., 117, 176 Kardakova, M. P., 207 Karguzova, A. M., 251 Karlamov, V. A., 54 Kaschig, J., 95 Kashman, Y., 6 Kataev, E. G., 256 Katagiri, N., 169 Kavunenko, A. P., 155 Kawamura, H., 229 Kawamura, M., 194 Kawamura, R., 230 Kawamura, S., 16, 245 Kawano, H., 230 Kawase, T., 110 Kazakova, N. D., 59 Kazimierczuk, Z., 172 Keat, R., 220 Keech, D. B., 133, 166 Keihl, R., 144 Keil, F., 33, 61 Kejtel, T., 90 Keiter, R. L., 20

Kelly, S., 110, 252 Kemp, G., 26 Kendurkar, P. S., 180 Kennard, O., 141, 268 Kennedy, L. D., 141 Kenyon, G. L., 148 Keren-Zur, M., 155 Kern, M., 76 Kerr, C. M. L., 237 Keschmann, E., 190 Kesling, H. S., 68, 177 Kezdi, M., 162 Khachatryan, R. A,, 23 Khalaturnik, M. V., 21, 180 Khalil, F. Y., 22 Khalitov, F. G., 263 Khan, N., 196 Kharlampidi, Kh. E., 31, 97 Kharrasova, F. I., 112 Khaskin, B. A., 121 Kheifets, L. Ya., 201 Khil'ko, M. Ya., 131, 254 Khorana, H. G., 169, 171, 173 Khotsyanova, T. L., 82 Khramtsov, Yu. I., 88 Khwaja, T. A., 159 Kibardina, L. K., 100, 131, 259 Kielanowska, M., 172 Kielbasinski, P., 121, 244 Kiely, D. E., 141 Kiener, V., 224, 227, 228 Kieselack, P., 30 Kim, C. U., 181 Kim, J. J., 62 Kim, M., 147 Kim, Y.J., 89 Kimura, T., 143 Kimura, Y., 37, 87 Kinas, R., 98, 109, 131, 250 King, R. B., 5 Kinoshita, M., 124 Kirby, G. W., 242 Kireev, V. V., 221, 229 Kirillov, Y.B., 82 Kirilov, M., 202, 264 Kirkpatrick, D., 13 Kirova, A. V., 273 Kirsanov, A. V., 19, 102,212 Kjse,. H., 183 Kishi, T., 260, 261 Kishore, N., 259, 272 Kisielowski, L., 186, 241 Kisilenko, A. A., 62, 214 Kisselev, L. L., 173 Kitaev, V. N., 229 Kitahara, Y., 240 Kitano. S.. 155. 158 Kitos, P. A., 176 Kitschke-von Gross, B., 267 Kitzrow, W., 88 Kjosen, H., 197 Klabuhn. B.. 81 Klaebe, A., 49 Klebanskii, A. L., 126, 205, 224 Kleemola, D., 27, 265 Kleid, D. G., 169, 173 Klein, M. P., 142, 249 Kleppe, K., 171 Kleppe, R., 171 Klier, K., 176 Knedel, M., 272

282

Author Itidex

Knoll, F., 12, 68, 177 Knopka. W. N., 229 Knorr, H., 181 Knorr, U., 181 Knorre, D. G., 165, 170,248 Knunyants, I. L., 34, 124, 17c 1LJ

KO, D., 249 Kobayashi, A., 267 Kobayashi, E., 227 Kobayashi, S., 87 Koberstein. R.. 165 Kochetkov; N.’K., 139, 154 Kodama, H., 219 Kodama, T., 219 Koekemoer, J. M., 195 Koenig, M., 39, 48, 118, 252 Koeppel, H., 74, 82, 254 Koerner, T. A. W., 139 Kossel. H., 173 Kogan; G.-A., 266 Kogan, V. A,, 218 Kohler, F. H., 179, 184 Kohler, S. J., 142, 249 Koizumi. T.. 105 Kojima, K.,’194 Kolata, G. B., 173 Koli, A. K., 181 Kolind-Anderson, H., 118 Kollman, P. A., 148 Kolodina, N. S., 273 Kolodvazhnvi. 0. I.. 178. 264’ Kolsky, V., 220 Kondo, T., 228 Kondranina, V. Z., 86 Kondratenkov, G. P., 126, 224 Konishi, Y., 194 Konovalov, E. V., 219 Konovalova, I. V., 38, 90, 107, 114 Konsowitz, L. M., 144 Koop, H., 64 Kopecny, R., 229 Koppes, W. M., 66 Korda, A. V., 176 Kori, S., 194 Kormachev, V. V., 65, 81, 83, 91 Kornilov, M. Yu., 19 Korol, E. L., 83 Korol’ko, V. V., 126, 205, 224 Koroteev, M. P., 89 Korovin, S. S., 254 Korshak, V. V., 224, 229 Koschatzky, K. H., 193 Koshutin, V. I., 86 Kosinskaya, I. M., 204 Koslov, E. S., 259 Kossyth, V. G., 71 Kost. A. A., 154 Kost; D., 125 Kosterin, E. A., 75, 90 Kostina, V. G., 57 Koszuk, J., 73, 87 Kotlarek. W.. 124 Kovac, J:, 200, 201 Kovalenko, N. P., 201 Kovalevskaya, T. V., 102, 123, 262 Kovenya, V. A., 21 1 Kozar, L. G., 201

-

I

,

Kozlov, E. S.. 34. 70. 205.

Kraevskii, A. A., 154, 248 Krasnova, T. L., 265 Kravchenko, V. V., 165 Krebs, B., 230 Krepysheva, N. E., 217 Kreshchenko, E. P., 262 Kresze, G., 202 Kricheldorf, H. R., 95 Krishnamurthy, S. S., 222, 268 Krivosheeva, I. A., 130 Krolikiewicz, K., 154 Krommes, P., 210 Kroon, P. A., 206 Kropachev, E. V., 119 Kroshefsky, R. D., 206 Kroupa, J., 229 Krupnov, V. K., 270 Krylov, L. V., 65 Krylova, A. I., 72 Kubayashi, S., 37 Kucherova, M. N., 205, 213 Kuczkowski, R. L., 240 Kuda, K., 219 Kudryavtsev, A. B., 1 Kudryavtseva, L. A., 251, 264 Kudryshov, A. A., 229 Kuehl, L., 148 Kugel, R. L., 225 Kuhtz, B., 223 Kukhanova, M. K., i54,248 Kukhar, V. P., 213 Kukhtin, V.A., 65,81,83,91 Kula, M.-R., 158 Kumada, M., 17 Kuniar, A., 171 Kumari, N., 180 Kunicky, J., 229 Kunz, H., 8 Kuramshin, I. Y., 51 Kurguzova, A. M., 264 Kurochkina, G. I., 230 Kurshakova, N. A., 36 Kushnir, V. N., 2 1, 180 Kutzbach, C., 149 Kutzelnigg, W., 33, 61 Kuznesof, P. M., 269 Kuznetsov, S. I., 82 Kyker, G. S., 228 Kyogoku, Y., 266 Kyuntsel’, 1. A., 213, 259 Lacey, J. C. jun., 167 Lachmann, U., 82, 254 Lafaille, L., 259 Lakshmikantham, M. V., 247 Laliberte, B. R., 228 Lammert, J. E., 175 Lamp, V., 162 Lampin, J.-P., 1, 53, 113 Lamprecht, W., 162 Landes, G. M., 176 Landick, R. C., 21, 1I90 Landini, D., 27 Langer, E., 3, 8, 60 Lanier, C. W., 229

Lapidot, Y . , 155 Lapin, A. A., 76 Larcheveque, M., 124 Lard, E. W., 230 Larin, M. F., 131, 254 Larson, J. E., 173 Larson, T. J., 141 Larsson, B., 164 Laskorin, B. N., 229, 273 Lastovzkii, R. P., 273 Latyshev, N. A., 274 Laurenco, C., 200 Laurent, H., 113 Lavrik. 0. I., 165 Lavrinen ko-Ometsinskaya, E. D., 265 Lawesson, S. O., 118, 124 Leader, H., 78 Lebedev. A. V.. 170 Lebedev; S. A.,’ 185 Lebedeva, A. S., 224 Lebedeva, E. N., 254 Lebedeva, N. M., 109 Le Corre, M., 37, 190 Le Dong Khai, 110 Leduc. M.. 46. 93 Lee, 6. R.; 248 Lee, J. B., 13 Lee, S., 32, 269 Lee, S. O., 252 Lee, Y.M., 147 Lees. R. G.. 169 Lehikoinen,’ A., 229 Lehmann, H.-A., 204 Lehmann, W. P., 209,256 Le-Hong, N., 195 Leitloff, M., 102 Lema, R. H., 232 Lemmen, P., 46, 259 Leonard, A., 130 Leone, S. A., 228 Lequan, R. M., 257 Lerman, C. L., 35 Leroux, Y., 38 Leshchev, V. V., 274 Lesiak, K., 109, 117, 131,257 Lesiecki, H., 17, 76 Lesnikowski, Z., 105 Letsinger, R. L., 169, 172 Letsou, A., 249 Levi, S., 202 Levin, D. H., 138 Levin, I. W., 62 Levin, Ya. A., 52, 59, 84, 261, 263 Levina, A. S., 248 Levy, R., 155 Levy, S., 175 Lewellyn, M. E., 124 Lewis, F. D., 232 Lewis, G. J., 104, 116 Lewis, P. A., 272 Liaaen-Jensen, S., 197, 203 Lienhard, G. E., 137 Liljas, A., 134 Lilly, M. D., 134 Lim, P. K. K., 42, 242 Lincoln, D. N., 248 Lindler, E., 17 Lindner, E., 76, 77 Lindner, H. J., 267 Lindner, W., 36 Linke, K.-H., 77 Liorber, B. G., 130

283

Author Index Lippsmeier, B., 232 Lisin, A. F., 88, 92 Listan, V. N., 179 Liteanu, C., 104 Litoshenko, N. A., 205 Littlefield, L. B., 34 Litvyakova, G. I., 119 Liu, 1. Y., 141 Livramento, J., 263 Llinas, J. R., 39 Lobanov, 0. P., 67 Loeb, L. A,, 176 Loeber, D. E., 196 Lons, J., 3, 266 Loew, L. M., 117 Loewen, P. C., 171 Loewenstein, P. M., 172 Lohrmann, R., 152, 167 Loktionova, R. A., 93, 208, 21 1 Long, R. C. jun., 255 Longinotti, L., 274 Lopusinski, A., 119, 120 Lora, S., 228 Lorberth, J., 210 Lornitzo, F. A., 147 Louisfert, J. A., 200 Lourens, G. J., 195 Lourens, R., 30 Lovan, J. S., 131 Loxon, B. A., 117 Luber, J., 28, 96, 209 Luckenbach, R., 17, 22, 76, 79,266,267 Luke, M. A., 274 Lukevic. 0.. 273 Lundgren, 8.K., 176 Lur’e, E. P., 34 Lutsenko, I. F., 2, 88, 97, 185

Luyten, W. C., 160, 170 Lux, F., 82 Lwowski. W.. 183 Lymn, R: W.; 268 Lynch, R. J., 259 Lysenko, V. P., 93, 208 Lysova, N. N., 265 Lythgoe, B., 74 McAuliffe, C. A., 2, 3, 4 Maccarone, E., 90 McConnell, H. M., 133 McDermott, C. P., 62 MacDiarmid, A. G., 20, 60, 267 Macdonell, G. D., 22, 73 McDowell, C. A., 234 McEwan, W. E., 11 McFarland, C. W., 119 McFarlane, H. C. E., 256 McFarlane, W., 256 McHale, A. H., 168 McIntosh, J. M., 25 Mack, D. P., 228 McKeever, B., 32, 269 McLaughlin, A. C., 133,248 Macleod, I., 5 MacMillan, J., 182 McNeely, G. W., 229 McNeilly, S. T., 56, 76 McRobbie, 1. M., 244 McVicker, E. M., 257 Mtirkl, G., 5 Magee, R. J., 102

Mahajan, K. P., 147 Mahomed, R. S., 229 Maier, L., 110, 111, 259,262 Maijs, L., 273 Maikuma, T., 229 Makarova, N. A., 271 Maki, H., 219, 229 Makihara, M., 221 Malavaud, C., 31, 97, 252 Malevannaya, R. A., 82 Malinowski, R., 91 Malinski, E., 81 Malkes, L. Ya., 201 Mal’kovskaya, T. M., 109 Mamakov, K. A., 80 Manafusa, T., 58 Manatt, S. L., 206 Manly, D. P., 17, 244 Mann, J. S., 203 Mannan, Kh., 222, 230, 268 Mannherz, H. G., 162 Manns, H., 226 Manojlovic-Muir, L., 5 Mansour, T. E., 139 Mantsch, H. H., 162 Marat, R. K., 34 Marchenko, A. P., 64 Marcondes, M. E. R., 232 Mardashev, Yu. S., 265 Marecek, J. F., 32, 46, 106, 269 Mareev, Yu. M., 255 Margulis, B. Ya., 256 Marians, K. J., 173 Marien, B. A., 15 Marino, J. P., 21, 190 Markham, J. L., 240 Markovskii, L. N., 62, 102 Markowska, A., 96, 102 Marquarding, D., 45, 46, 88 Marr, G., 72 Marshall. J. A., 124 Marshall, W. E., 249 Marsi, K. L., 21, 22, 266 Marsmann, H. C., 228 Martensen, T. M., 139 Martin, O., 195 Martin, P. R., 267 Martin, R. B., 142 Martin, R. H., 20, 199 Martinengo, S., 230 Martynyuk, A. P., 64, 207, 216 Marumoto, R., 158 Maryanoff, C. A., 95 Masamune, S., 181, 188 Masilamani, D., 95 Masler, W. F., 3 Mason, R., 9, 268 Masse, G. M., 25 Massey, V., 135 Mastryukova, T. A., 255, 259 Masuda, I., 230 Masumoto, H. T., 274 Matei, A. A., 83, 270 Mathey, F., 1, 7, 27, 53, 54, 72, 80, 113, 265 Mathis, F., 259 Mathis, R., 264 Matrosov, E. I., 207 Matson, J. A., 233 Matsuda, T., 124 Matsuura, H., 20, 186, 258

Matthes, D., 5 Matton, R. W., 228 Matveev, 1. S., 9 Matzinger, D., 16 Mawby, R. J., 238 Maxson, R. E. jun., 175 Maycock, A. L., 135 Mazhar-U1-Haque, 268 Mazo, A. M., 173 Mazzaracchio, F., 274 Meakin, P., 254 Med ici, A,, 226 Medrano, J. A., 105 Medved, T. Ya., 71 Medvedeva, M. D., 100,103 Meek, D. W., 5 Megera, I. U., 183 MClJCr, J., 8, 80 Melaugh, R. A., 273 Mel’nikov, N. N., 104, 107, 110, 121, 124 Menezes, L. C., 164 Meppelder, F. H., 258 Merour, J. V., 127 Merregaert, J., 173 Merrill, G. B., 181, 212 Messeguer, A., 203 Mesyats, S. P., 83, 273 Meth-Cohn, O., 244 Meussdoerffer, J. N., 275 Meyer, H., 250 Meyer, H. J., 124 Meyer R. B. jun., 153, 159 Meyers, A. I., 246 Meyers, W. H., 5 Mhala, M. M., 119 Mian, A. M., 153, 159 Micetich, R. G., 242 Michalik, J., 262 Michalski, J., 40, 94, 96, 101, 102, 115, 117, 119, 120, 121, 129, 244, 252 Michel, W., 12, 68 Middleton, T. B., 52 Midorikawa, T., 230 Mieczkowski, J., 15 Mielczarek, D., 131, 257 Mikelajczyk, M., 91 Mikhailov, S. N., 157, 171 Mikhailova, 0. B., 104, 107 Mikke, R., 172 Mikolajczak, J., 40, 94, 115, 121. 244. 252 Mikolajczyk, M., 102, 121, 131, 201, 244, 268 Mikul‘shina, V. V., 28, 212 Milbrath, D. S., 33, 85 Mildvan, A. S., 176 Miles, H. T., 153, 172, 249 Miles, M. G., 11, 89, 247 Milker, R., 14,.51, 70, 211 Miller, G. A., jun., 146 Miller, J. A., 56, 57, 67, 76 Miller. J. P.. 159 Miller; R. C:, 171 Millington, D., 5, 223, 236 Mims, L. C., 274 Minamoto, K., 171 Min Jou, W., 173 Mirault. M.-E.. 175 Mironova, L. V., 20 Mise, T., 17 Mishra, S. P., 62, 237 Misunii, S., 245

Author Index

284 Mitachi, S., 17 Mitchell, J. D., 16, 79, 256 Mitchell, J. W., 83 Mitchell, K. A. R., 234 Mitchell, P., 143 Miura, K., 154, 174 Miyake, H., 194 Miyake, K., 124 Miyake, T., 169 Miyano, M., 178 Miyashita, M., 194 Mizuno, M., 230 Mizuno, Y., 155, 158 Mizushima, M., 244 Moder, T. I., 148 Modolell, J., 164 Modro, T. A., 81, 123 Mcedritzer, K., 54, 72 Moffatt, J. G., 195 Moiseeva, 0. A., 83 Mojski, M., 83 Mokeeva, V. A., 213, 259 Molemans, F., 173 Molyavko, L. I., 270 Momchilova, S., 202 Momii, R. K., 117 Moninari, H., 27 Montanari, F., 27 Montenarh, M., 216 Moore, G. Y., 225, 228 Moradpour, A., 20 Moran, T. A., 74 Moras, D., 134 Morbach, W., 12, 68 Moreland, C. G., 34 Morelli, A., 160 Moret, V., 147 Morgan, W. E., 254 Mori, K., 194 Moriarty, R. M., 240 Morozov, L.L., 255 Morr, M., 158 Morren, G., 20 Morris, D. L., 19 Morrison, J. D., 3 Morrow, C. J., 3 Morse, J. G., 34, 52 Morse, K. W., 34, 52 Morton, J. R., 237, 262 Mosbach, K., 160 Moskalevskaya, L. S., 11 1 Moskva, V. V., 66, 67, 110, 263 --M osolov, N. N., 270 M ouheigh, T., 41, 97, 252 M oulton, C. J., 9 M oyle, B., 9 M ueller, G., 274 M ueller, R., 256 M uir, K. W., 5 M uirhead, H., 146 M[ukaiyama, T., 16, 168, 240 M ukhamedova, L. A., 110 M ukhametov, F. S., 57, 267 M lukhtarov, A. Sh., 261 M[ukmenev, E. T., 254, 270, 171

L I 1

Muller, B., 199 Muller, G., 80 Muller, H.-D., 52 M y y z , A., 39, 48, 49, 118, LJL

Murahashi, S . I., 25 Murch, R. M., 230

Murray, D. A. J., 274 Murrel, L. L., 5 Musco, F., 148 Mushika, Y., 105, 152 Musin, R. Z., 271 Musina, A. A., 39, 254 MUSSO,R., 174 Muthukrishnan, S., 174 Mutin, R., 2 Muylle, E., 51 Myasnikova, L. G., 88 Myers, T. C., 11 1, 141,249, 254 Myles, A., 155, 156 Mynott, R. J., 248 Naae, D. G., 68, 177 Naaktgeboren, A., 80 Nabi, S. N., 223 Nagai, K., 228, 229, 230 Nagakura, I., 67 Nagura, T., 171 Nagyvary, J., 159 Nakabayashi, T., 16, 245 Nakagaki, M., 275 Nakahama, T., 229 Nakahara, A., 165 Nakahara, H., 266 Nakajima, Y., 168 Nakamura, N., 194 Nakamura, Y.,228 Nakayama, S., 234 Nambudiry, M. E. N., 74 Nandi, K., 17 Narang, S. A., 169, 170 Narita, M., 23 Nasakin, 0. E., 91 Naumov, V. A., 269 Navech, J., 259 Nawbudiry, M. E. N., 74 Nazvanova, G. F., 67, 110, 263 Nechaeva, M. A., 110 Neil, I. G., 260 Neilson, R. H., 64 Neilson, T., 169 Nekrasov, Yu. S., 72 Nelson, D. J., 237 Nelson, S. M., 18 Nesmeyanov, N. A., 20, 28, 72, 212 Nesterenko, V. D., 86, 209 Nesterov, L. V., 217 Neudert, B., 12 Nevinsky, G. A., 165 Newkome, G. R., 51 Nguyen Thanh Thuong, 104, 127 Nibler, J. W., 82 Niecke, E., 86, 214 Niecke, W., 100 Niederberger, W., 142 Nielsen, H., 274 Nifant’ev, E. E., 86, 89, 259 Nikitin, V. M., 131, 254 Nikitina, V. I., 91, 114 Nikolaev, A. F., 221 Nikonova, L. Z., 95 Nishigaki, S., 192 Nishikawa, S., 171 Nishikida, K., 235 Nishimura, T., 158 No, B. I., 112 Noeth, H., 5

Nolan, T. J., 13 Noltmann, E. A., 144 Nomura, A., 155 158 Normant, H., 124, 142, 201 Norpoth, K., 274 Norris, K. E., 169 Norton, L. I., 147 Noth, H., 96 Novetny, A., 229 Novikova, A. N., 221 Novikova, Z. S., 2, 97 Novobilskjr, V., 220 Novruzov, S. A., 66 Noyes, B. E., 175 Nozawa, R., 159 Nunn, M. J., 57 Nuretdinov, I. A., 260, 263 Nuretdinova, 0. N., 95, 124 Nussbaum, A. L., 164 Nwe, K. T., 74, 233 Nwokoro, N. A., 134 Oae, S., 16 Oakley, R. T., 219, 231 Oberhammer, H., 33,62,269 Obermaver. A. S.. 230 O’Connbr, ’E. M.,’ 16 Oda, M., 240 Odom, D. G., 167 Odom, J. D., 256 Oehling, H., 240 Ofitserov, E. N., 209 Ofitserova, E. Kh., 38, 77 Ogata, H., 135 Ogata, T., 20, 186, 258 Ogawa, M., 196 Ogawa, S., 249 Ogilvie, K. K., 158, 170 Ohashi, T., 13, 70 Ohbe, Y., 124 Olinishi, Y.. 143 Ohno, A., 123 Ohtsuka, E., 168, 169, 171 Oka, S., 143 Okada. H.. 228. 229.230 Okada;T.,’58 ’ ’ Okamoto, Y., 53, 58,86,240 Okazaki, H,, 106 Okazaki, R., 76,234, 239 Okruszek, A., 98, 117, 131, 252, 257 Okutani, Y.,230 Olah, G. A., 119 Olast, M., 262 Oleinik, D. M., 102 Olejnik, J., 96, 102 Oliver, J. E., 187 Olsen, K. W., 134 Omachi, A., 249 Omelanczuk, J., 121, 244 Oosawa, Y.,267 Orgel, L. E., 152, 167 Orlacchio, A., 136 Orlos, V. Y., 185 Orlovskii, V. V., 91 Oro, J., 167 Orwoll, E. F.,229 Osellame, M., 227, 228 Osipov, 0. A., 82, 83, 218 Osipova, L. F., 224 Osokin, D. Ya., 260 Ostoja Starzewski, K. H. A., 266 Ostrowski, K., 262

Author Index

285

Oswald, A. A., 5 Otsubo, T., 245 Ovakimyan, M. Zh., 23 Overman, J. D., 16 Overman, L. E., 16 Ozawa, S., 230 Paddock, N. L., 219, 231 Padmanadhan, R., 173 Padwa, A., 192 Paetzold, R., 82 Palmer, M. H., 27 Palovcik, R., 201 Panasyuk, A. I., 207 Panet, A., 171 Panitz, N., 160 Pankiewicz, K., 109 Panosyan, A. G., 266 Pappa, R., 134 Parmeggiani, A., 164 Parrott, M. J., 236 Parsons, S. M., 146 Parsons, T. F., 144 Pasternak. A., 248 169

119 PauLen,’ H., 85 Pavlenko, N. G., 213 Pavlov, V. A., 130 Pavlycheva, E. V., 18 Peacock, L. A,, 263 Pedersen, E. B., 124 Peel, J. B., 270 Penades S., 165 Pen’kovikii, V. V., 214, 261, 265

Peppard, D. J., 199 Pepperman A. B., jun., 8,78, 79.100 Perini, F., 153 Perks, M., 18 Perregaard, J., 124 Perret, F., 195 Perrin, E. D., 27 Perrings, J. F. M., 238 Pesnelle P., 199 Pessine,’F. B. T., 269 Pesso, J., 202 Pestova, T. A., 100 Pestunovich, V. A., 131, 254 Peters. G. M.. 200 Petersen, G. R., 172 Petrenko, V. S., 207 Petrov, A. A., 36, 54 Petrov, A. I., 261 Petrov, E. A., 273 Petrov, E. S., 83, 273 Petrov, G., 264 Petrov, K. A., 71, 110 Petrov, K. I., 82 Petrova. J.. 200. 202 Petrovskii,’ P. V., 28, 212, 255 259 Pettei: M., 239, 262 Petty S. T 16 Pezzik G.,’>27, 228 Pfleidirer, W., 155, 156, 157, 248

Phili&

D. I., 35, 254

Phinney, B. D., 182 Phisuthkul, S., 28 Piechucki, C., 199 Piekos, A., 81 Piers, E., 67 Pietrusiewicz, K. M., 73, 87 Pilette, J. F., 183 Pilyugin, G. T., 19 Pinchuk, A. M., 64, 102, 123, 211, 262 Pinna, L. A., 147 Pinnavaia. T. J.. 249 Pioch, J., ’123 ’ Piraux, M., 183 Pirisi, F. M., 27 Pisanenko. N. P.. 204 Piskala, A:, 181 ’ Pittman, C. U. jun., 23 Pitzer, K. S., 62 Plantema, 0. G., 202 Platt, E., 234 Plyashkevich, Yu. G., 1 Pobedimskaya, M. V., 52 Pocar, D., 191 Podlahova, J., 3 Podo, F., 248 Pogonowski, C. S., 194 Pohl, S., 100, 214, 230 Poitrenaud, C., 83 Polder, W., 230 Polezhaeva, N. A., 39,44, 86 Polikardov, Yu. M., 71 Poling, M., 137, 267 Pollard, G., 7 Polyakova, I. A., 273 Pomerantz, A. H., 165 Pominov, I. S., 51 Pommeret-Chasle. M. F., 46,93 Pongs, O., 167 Ponomarev, S. V., 185 Porte, A. L., 213, 220 Porter, J. W., 147 Post. M. L.. 141. 268 Pouet, M. J., 257 Poulin, D. D., 269 Poulter, C. D., 147 Povolotskii, M. I., 211, 213, 259 Pozhidaev. V. Ma, 114 Prasad, V:A. V.,‘39 Prajer, K., 111 Pratt, T. M., 242 Predvoditelev, D. A., 86 Preston, K. F., 237, 262 Preston. R. K.. 166 Profous, Z. C.,‘ 271 Prons, V. N., 205, 224 Proskurnina, M. V., 88 Prosperi, G., 134 Prousek, J., 200 PrvstaS. M.. 148 Pudles,‘J., 164 Pudovik, A. N., 31, 38, 41, 48, 54, 76, 77, 86, 90, 91, 97. 103. 107. 114. 129. 131. 9

48, 110.

252, 267 Purrello, G., 186 Pyrkin, R. I., 52

Quail, J. W., 147 Quast, H., 113 Quin, L. D., 6, 7, 74, 250, 251. 252 Qureshi, A. A., 147 Rachon, J., 89, 111 Racker, E., 138 Radda, G. K., 133,137,142, 164. 248.249 Radeglia, R.,251 Radics, L., 12, 68 Raevskii, 0. A., 263 Raeymaekers, A., 173 Raghunathan, P., 234 Rahman, A., 67 Raidt, H., 274 Rajbhandary, U. L., 171 Rakov, A. P., 75, 90 Rakow, D., 134 Raksha, M. A., 110 Ramage, R., 182 Ramamoorthy, B., 169, 171 Ramirez, F., 32, 39, 46, 106, 259. 268.269 Range, P.,’l80 Rao, A. V. R., 122 Rashkovich, L. N., 256 Ratliff. R. L.. 172 Ratts,’K. W.: 84, 200 Razjivin, A. P., 154 Razumov, A. I., 57, 66, 67, 110, 130,273 Razumova, N. A., 36 Razvodovskaya, L. V., 124 Re, L., 134 Rebrova, 0. A., 28,212 Redoules, G., 18, 60 Reed, M. D., 130 Rees, J. M., 220 Reese, C. B., 156, 170 Reeve, R. N., 259 Regitz, M., 71, 91, 128 Reichman, S., 51 Reid, T. W., 144 Reimann, R. H., 5 Reiness, G., 163 Reisel L 212 Reitz,’G.*,’ 155, 156, 157, 248 Remisov, A. B., 5 1 Repina, L. A., 211 Repke, D. B., 195 Reutov, 0. A., 20, 28, 212 Reutrakul, V., 28 Revankar. G. R.. 153 Revel, M.’, 174 ’ Reynard, K. A., 227, 228 Reynolds, C. D., 268 Reznik, V. S., 52, 118 Rhaese, H.-J., 163 Rho. M. K.. 89 Rich, A., 153 Richard, B., 38 Richards R. E., 133, 137, 248.249 Richardson, G., 14 Richter, W., 179 Ridgway, R. W., 118 Ried, W., 181 Rieke, E., 160 Rieser, J., 179 Riess, J. G., 64, 65 Riley, J. E., 83 Rilling, H. C., 147, 148

Author Index Rimpler, M., 165 Ritchie, G., 133. 248 Riva, F., 136 Rivalle, C., 200 Rizpolozhenskii, N. I., 56, 57 Robas, V. I., 28, 212 Robert, D. U., 64, 65 Robert, J. B., 51, 99, 257 Roberts, B. P., 235,236,238, 2 60 Robertson, B. E., 147 Robins, R. K., 153, 159 Roca, A., 203 Rodionova, L. S., 54 Roschenthaler, G.-V., 49, 58,206 Roesky, H. W., 204,221,223 Rossner, E., 167 Rogers, P. E., 235 Rogovin, Z. A., 221 Rogozhin, S. V., 266 Rojhantalab, H., 82 Rokhlin, E. M., 34 Rokos, H., 156 Romanenko, E. A., 220, 260 Romanov, G. V., 76 Romanov, L. M., 230 Ronman, P. E., 28 Ropuszynski, S., 105 Rose, H., 226, 229 Rose, K. A,, 228 Rose, S. H., 228 Rosenberg, M., 174 Rosenberger, H., 256 Rosenburg, H., 142 Rosenthal, A. F., 84 Rosenzweig, S., 146 Rosin, H., 239 Rosini, G., 226 Ross, A. H., 133 Rossknecht, H., 209, 256 Rossmann, M. G., 134 Rossodivita, A., 134 Roth, W.-D., 45 Rottman, F., 172 Rousseau, R. J., 153 Rout, M. K., 265 Rowley, A. G., 242 Rowohl-Quisthoudt, G., 165 Roychoudhury, R., 174 Rozhdestvenskaya, I. T., 51 Rozhkova, N. K., 97 Rozinov, V. G . , 65, 109 Rubinstein, M., 168, 169 Ruch, E., 202 Rudavskii, V. P., 205, 21 3 Rudolf, R. W., 51 Rudolph, S. A., 139, 165 Runge, W., 202 Ruppert, I., 216 Russell, D. R., 32 Russell, J., 165 Rust. M. K.. 193 Ruston, S., 74 Rybkina, V. V., 65, 109 Rycroft, D. S., 251 ’

Saalfrank, R. W., 189 Saatsasov, V. V., 82 Sable, H. Z., 137 Sacher, R. E., 228 Sadler, P. A., 32, 242 Sadykov, A. A., 251

Saeguss, T., 37, 87 Safin, I. A., 260 Safiullin, R. K.,255 Saiki, K., 196 Saito, H., 221, 225, 229 Saito, T., 267 Sakai, K., 194 Sakakibara, T., 27 Sakamoto, A., 229 Sakata, Y., 245 Sakurada, I., 227 Sakurai, H., 53, 58, 86, 237, 240 Salach. J. I., 135 Salakhutdinov, R. A., 57, 66, 67, 110, 273 Salhany, J. M., 249 Salikhov, I. Sh., 118 Salomon. R. G.. 181 Samama,’ J. P , 134 Samarai, L. I., 34, 70, 213 Sammes, P. G., 240 Samitov, Yu. Yu., 41, 131, 254, 255, 256. 258, 259 Samiuzzaman, Q. M., 262 Sanadi, N. E., 181 Sancaktar, E. A., 187 Sanchez, M., 41, 97, 252 Sandnieier, D., 177, 190 Sanin, P. I., 102 Saphyullin, R. Kh., 258 Sarma, R., 32, 248, 249, 269 Sartori, P., 55, 76 Sasaki, T., 166 Sasaki, Y . , 159, 267 Sasse, E. A., 274 Satge, J., 18, 60, 61 Sato, A., 16, 245 Sato, S . , 200 Sato, T., 233, 245 Satra, S . K., 240 Satterthwaite, A.. 122 Sau, A. C., 222 Sauer, J. D., 51 Saunders, J. E., 51, 262 Savignac, P., 38, 122, 123, 142. 200.201 Sawai; H.,‘167 Sazanova, A. A., 83 Scaiano, J. C., 232, 239 Scarlata, G., 90 Schaaf, T. K., 194, 202 Schabl, L., 45, 88 Schachter, H., 134 Schack, C. J., 70 Schadow, H., 222 Schafer, G., 165 Schafer, H., 20, 60, 267 Schafer, W., 27, 29, 265, 272 Schaffer, O., 30, 80, 239 Scharf, D. J., 45, 96 Schatz, J., 51 Schemer, K., 207, 254, 261 Scheinker, V. S., 173 Scheler, H., 222 Scherer, 0. J., 96, 208 Scherrer, K., 175 Schickenader, H., 210 Schlak, O., 35, 206 Schleinitz, K. D., 82, 254 Schliebs, R., 275 Schlimme, E., 162 Schlosser, M., 18 I Schmii!, E., 219, 220 ’

Schmid, G., 177, 190 Schmid, H., 125 Schmid, J. P., 183 Schmidbaur, H., 178, 173, 184, 185 Scimidpeter, A., 28, 32, 41, 96, 209, 227, 256, 269 Schmidt, A., 208, 219, 262 Schmidt, U., 233 Schmidt, M. F. G., 139 Schmidt-Dunker, M., 102 Schmutz. J. L.. 223 Schmutzler, R:, 34, 35, 49, 58, 64, 206 Schneider, N. S., 204, 228 Schnell, A., 22, 186 Schoffstall, A. M., 15I Schonbrunn, A., 135 Schott. H.. 173. 274 Schrader, E., 165 Schultz, P., 221, 224 Schulz, D. N., 11 Schulze, J., 251 Schumann, H., 12, 59 Schurig, V., 2 Schwartz, P., 1 Schwarz, G., 266 Schwarz, M., 187 Schwarz, R. T., 139 Schwarz, W., 224, 228 Schwarzenbach, D., 196 Schweig, A., 27, 29, 260, 265 Schweiger. J. R.. 206 Schweizer: E. E.. 82. 179, 250, 253 Schweng, J., 189, 218, 2 19 Schwiezer, J. , 183, Scollary, G., 9 Scott, C. A., 10 Sebesta. K.. 148 Sedlov,’A. I., 211, 219 See], F., 251 Seela, F., 158, 159 Seelig, J., 142 Seely, P. J., 133, 137, 248 Sefiullin, R. K., 255 Segall, Y . , 78 Seguin, F. P., 25 Seifert, J., 270 Sekija, T., 171 Sekine, M., 92 Sekine, Y . , 86, 233 Selivanova, A. S., 86, 209 Selve, C . , 13, 93 Senga, K., 192 Sengupta, K. K., 62 Sennyey, G., 7 Seno, M., 183 Senoura, M., 219 Serebrennikova, G . A., 266 Sergeev, V. S., 121 Seshadri, T. P., 141, 26s Sevilla, M. D., 239, 262 Shabarova, Z. A., 153 Shagidullin, R. R., 262, 263, 264 Shakirov, I. Kh., 262 Shannon, P. V. R., 244 Shaposhnikov, I. G., 213 Sharina, R. A., 19 Sharma, R. N., 119 Sharma, R. P., 242 Sharov, V. N., 126, 205, 224 Sharp, D. W. A., 5 I

,

287

Author Index Sharp, J. T., 242 Shalalov, V. V., 227 Shatenshtein, A. I., 83, 273 Shatkin, A. J., 174 Shaver, A., 70 Shaw, B. L., 9 Shaw, I. M., 66 Shaw, P. J., 146 Shaw, R. A., 54, 204, 215, 220, 222, 223,230, 268 Shcherbina, T. M., 83, 273 Shchukina, L. I., 54 Sheard, B., 144 Shechter. H.. 181. 212 Sheer, M.L.; 2% Shek, V. M., 270 Sheldrick, W. S., 32,206,269 Shelganova, N. N., 83, 273 Shelest. V. V.. 19 Shen, Q., 269‘ Shepeleava, E. S., 102 Sheppard, D., 234, 260 Sherman, W. R., 141 Shermergorn, 1. M., 45, 86, 131, 259 Shevchenko, V. I., 204 Shevchuk. M. I. .21.23. . , , 75., 180, I83 Shiau, We-I., 11, 251 Shibaev, V. N., 139, 154 Shilov, I. V., 89 Shimada, Y., 168 Shimotohno. K.. 174 Shin. C.. 86.’ 233 Shiori, T., 123 Shipley, G. G., 268 Shipov, A. E., 255 Shiraishi, S., 183 Shishkin. V. E.. 112 Sh.-Mukhtarov; A., 261 Shokol, V. A., 81, 208, 270 Shostenko, A. G., 52 Showronska, A., 40, 244 Shpak, S. T., 23, 75 Shriver, D. F., 269 Shubina, T. N., 248 Shugar, D., 172 Shulman, R. G., 249 Shuman, D. A., 159 Shumyantzeva, V. V., 153 Shvets, A. A., 82, 83, 218 Shvetsov, Yu. S., 118 Sicka, R. W., 228 Siddall, T. H., 78, 79, 100 Sidlova, L. N., 213 Sidorova, E. E., 111 Sidorova, N. S., 155 Sidwell, R. W., 153 Siedle, A. R., 89, 247 Siegel, M., 104 Siewers, I. J., 119 Sigalov, M. V., 13 1, 254 Sigel, H., 164 Silvano, L., 227 Silver, E. H., 183 Silverman, J. B., 147 Sim, E., 248 Simon, L. N., 159 Simoncsits, A. 152, 162 Simonnin, M. P., 257 Singer, B., 154 Singer, T. P., 125 228 Singler, R. E., ~04, Sinitsa, A. D., 19, 81

Sinou, D., 2 S/tdikova, T. Sh., 67, 110 Sizov, Yu. A., 124, 125 Skapski, A. C., 268 Skorobogatova, M. S., 261 Skorobogatova, S. Ya., 2, 97 Skorovarov, D. I., 227, 229 Skowronska, A., 94, 115, 121,252 Skrzypzynski, Z., 101, 129 Sledzinski, B., 242 Sleziona, J., 75 Sliwowski, A., 262 Sloan, D. L., 176 Slotin, L. A., 166 Smalanoff, J., 192 Smegal, J., 220 Smeltz, K. M., 227, 228 Smiley, E. I., 134 Smirnov, V. A., 86 Smirnov, V. V., 39,44, 86 Smissman, E. E., 66 Smit, W. M. A., 270 Smith, D. A., 172 Smith, D. G., 10 Smith, D. J. H., 10, 17, 32, 76 Smith, G. D., 21, 266, 268 Smith, M., 153, 158, 168 Smrt, J., 157, 171 Snider, T. E., 267 Snyder, S. L., 146 Sobanov, A. A., 90 Sobczyk, L., 82 Sobhi, D., 183 Sodler, P. A., 268 Sohafer, W., 260 Soifer, G. B., 213, 259 Sokal’skaya, L. I., 273 Sokolov, E. I., 205 Sokolov, L. B., 88, 112 Sokolova, N. I., 153 Soleiman, M., 23 Solov’ev, N. G., 204 Solovova, 0. P., 224 Soloway, A. H., 183 Somieski, R., 212 Sondheimer, F., 199 Sonnet, P. E., 187 Soodsma, J. F., 274 Sorm, F., 148 Sorokina, A. A., 259 Soulen, R. L., 177 Soussan, G., 60 Sowa, T., 159 Sowerby, D. B., 223, 230 SDeckamD. W. N.. 181 Specker, -H., 226, 228 Spencer, H. K., 247 Spencer, R., 1 3 5 Sperling, J., 165 Sperow, J. W., 144 SDessard. G. 0.. 181 Spirin, A. S., 175 Spohr, G., 175 Sprecher, M. S., 125 Springer, J. P., 33, 85 Springs, B., 90, 110 Sprinzl, M., 161 Srivastava, B. I. S., 172 Stachowicz, W., 262 Stadelmaon. W.. 206 Stahl, J., 161 ’ Stahly, E. E., 230

Stankiewicz, T., 32, 206 Stanmfjord, J. V., 274 Stark, G. R., 175 Start, J. F., 229 Stawinski, J., 170 Stealey, M. A., 178 Stec, B., 131, 257 Stec, W., 31,66,98, 109, 117, 119, 120, 131, 132, 250, 251,252, 257 Steffens, J. J., 119 Stegmann, H. B., 41, 64, 207, 254, 261 Steirl, P., 81 Stelzer, O., 206 Stepanek, A. S., 212, 216 Stepanov, B. I., 1 Stepashkina, L. V., 56 Stephens, J. C., 163 Stephens, M., 62 Stern, P., 259 Stern, R., 17 Sternbach, H., 166 Stevens, D., 4 Stokes, B. O., 143 Stransky, W., 178, 180, 193 Straughan, B. P., 52 Strelko, V. V., 265 Struchkov, Y. T., 131, 132, 267,268 Struver, W., 13, 14, 69 Strunk, U., 183 Struve. G. E.. 148 Stubbe, J., 140 Stuber, F. A., 200 Stuckwisch, C. G., 218 Stukalo, E. A., 62 Sturtevant. J. M.. 139 Subramanian. N.: 126. 127 Subramanyam, V:, 183 Suciu, D., 210 Sudakova, T. M., 77 Sudoh, R., 27 Suerbaev, Kh. A., 259 Suganama. T. S.. 228 Sugasawa,’S., 13’ Sugimoto, S., 137 Sugiura, M., 171 Sugiyama, T., 168 Sukhorukov, B. I., 261 Sullivan, J. M., 221 Sultanova, D. B., 57, 273 Sund, H., 165 Suschitzky, H., 244 Sussman, J., 100 Suter, C., 199 Suvalova, E. A., 113 Suzuki, H., 58 Suzuki, N., 159 Suzuki, S., 165 Suzuki, T., 272 Suzuki, Y., 58 Sviridov. E. P.. 19 Swee Hock Goh, 10 Swindles, M., 32 Swire, S. J., 32, 242, 268 Switzer, R. L., 146 Sykes, B. D., 133 Symmes, C. jun., 6, 7, 74 Symons, M. C. R., 51, 62, 234, 236, 237, 238 Szabnbai. Z.. 221 Szabo, L:, 138 Sznrek, W. A,, 15

Author Index Szechner, B., 15 Szele, I., 35, 254 Tachibana, S., 123 Taguchi, Y.,105, 152 Tait, B. S., 32, 42, 43, 242, 243.244.253. 268 Takahashi; H., 267 Takaku, H., 16,152,168,245 Takeds, M., 274 Takei, H., 124 Takeuchi, I., 228, 229, 230 Takeva. T.. 171 Takiiawa, T., 11, 88 Tamura, K., 76, 239 Tan, H. W., 98,252 Tang, Y.-N., 240 Tanigawa, Y., 25 Tanswell. P.. 176 Tantasheva,’F. R., 256 Tarchini, C., 181 Tarzivolova, T. A., 130 Tate, D. P., 227 Tatemitsu, H., 245 Taubert, R., 219 Taylor, H. C., 160 Taylor, J. D., 187 Taylor, R. C., 2 Taylor, R. P., 249 Taylor, S. S., 134 Taylor, W., 267 Tebby, J. C., 22, 186, 272 Teichert, H., 60 Teichmann, H., 251 Telefus, C. D., 39 Telegin, G. F., 229 Temkina, V. Ya., 273 Temnikova, G. S., 107 Terands, K., 270 Terauchi, K., 237 Terazawa, H., 228 Terekhova, M. I., 83, 273 Terent’eva, S. A., 31, 41, 48, 97 Tertyshnyi, V. N., 207 Tewari. R. S.. 180 Tezuka, T., 171 Tkavard, D., 54, 72 The, K. I., 34, 255, 269 Thelandei, L., 164 Thenn. W.. 210 Thiem; J., 8 5 Thomas, B., 222 Thomas, G. J., jun., 263 Thompson, J. A., 240 Thomsen, I., 124 Thornton. J. M.. 176 Ticozzi, C., 188 Tideswell, J., 74 Tikhonina, N. A., 207 Tilichenko, M. N., 18 Timofeeva. G. I.. 207 Timokhin.’B. V..’ 20 Tjessem, K.,272 Tkatchenko, I., 2 Tochilkina, L. M., 212 Todesco. P. E.. 7. 128 Tomoskozi, 1,,‘12, 68 Tolkunova, V. S., 72 Tolman, R. L., 153 Tolochko, A. F., 183 Toma, N. D. A., 2 Tomasz, J., 152, 162 Tomlinson, A. J., 269 ’

Tomofuji. I., 196 Tong, W. P., 11 Torgasheva, N. A., 121 Torgomyan, A. M., 23 Torrence, P. F., 172 Toscano, V. G., 232 Toube, T. P., 196 Traylor, T. G., 178 Tremper, A., 192 Trentham, D. R., 162 Tret’yak, M. G., 121 Trippett, S., 17, 32, 34, 62, 76, 91 Triskina, L. B., 59 Trizno, M. S., 221 Trofimov, B. A., 131, 254 Trommer, W. E., 133, 164 Tronchet, J. M. J., 195, 196 Trotter, J., 23 1 Trutneva. E. P.. 264 Tsukida,’K., 196 Tsung, S. H., 274 Tsvetkov, E. N., 82, 83, 265, 273 Tsyryapkin, V. A., 266 Tuemmler, W. B., 229 Tuinstra, H., 21 Tulyaganov, S. R., 97 Tundo, P., 27 Tuong, H. B., 181 Tupitzyn, I. F., 273 Turano, C., 136 Turcant, A.. 37 Turel, R. J.; 274 Tusa, P. P., 144 Tweddle, N. J., 32, 43, 243, 244,268 Tv. N. G.. 162 Tybganova, M. A., 221 Tyutyulkov, N., 264 Tzschach, A., 7 Uchic, M. E., 172 Uchic, J. T., 172 Uchiyama, M., 274 Ueda, T., 154 Uesugi, S., 171 Uetrecht, J. P., 199 Ugi, I.. 45, 46, 88, 106, 259 UI-Hasan, M., 222 Ullmann, R., 96 Ulmschneider, K. B., 41, 64 Ulrich, H , 200 Ulrich, J., 271, 272 Ungureanu, A., 104 Uno, H., 159 Usher, D. A., 168 Utebaev, U., 34 Uznanski, B., 31, 109, 117, 119, 131, 251,257 Vaisberg, M. S., 255 Vallejos, R. H., 144 Van Bolhuis, F., 231 van Boom, J. H., 155, 156, 160, 170 Van de Grampel, J. C., 231 Van de Griend, L. J., 5 1 van den Berg, F. M., 175 van den Berghe, A., 173 van-der-Helm, D., 82, 267 Van-der-Kelen, G. P., 51, 82 van der Marel, G., 155 Van der Veken, B. J., 263 van de Sande, J. H., 171, 174

van Deursen, P. H., 156, 170 van Dijk, J. M. F., 238 Van Duuren, B. L., 240 Vandyukova, I. I., 263 van Straten, A. J., 270 van Wazer, J. R., 50, 53, 111, 254, 256 Vargas, L. A., 84 Vasilenko, I. A., 266 Vasilenko, S. K., 175 Vasil’eva, T. V., 81 Vaskovskii, V. E., 274 Vhsauez. D.. 164 Vasideva-Murthy, A. R., 222, 268 Veeger, C., 137 Veltmann, H., 12, 68 Venkataramu, S. D., 22, 73 Verbanov. S. G.. 83 Verkade, J. G.,’33, 51, 85, 98, 206, 250 Vermeer, H., 29, 260 Vermeer, P., 8, 80 Vettman, H., 177 Vicic, J. C., 228 Vig, A. K., 203 Vig, 0. P., 203 Vignais, P. V., 143 Vilceanu, N., 221 Vilceanu, R., 221, 224 Vil’chevskaya, V. D., 72 Vink, A. B., 160, 170 Vinogradov, L. I., 114 Vinogradova, S. V., 224 Vinogradova, V. S., 92, 255 Viswamitra, M. A., 141, 268 Viswanathan, N., 180 Vizel, A. O., 54, 57, 126, 270 Vladimirskaya, N. B., 86 Vogt, W., 272 Voigt, R. F., 17 Voitsekhovskaya, 0. M., 251, 265 Volante, R. P., 148 Volckaert, G., 173 Volkova, L. V., 137 Vollhardt, K. P. C., 198 Vollmer, H., 229 Volodin, A. A., 229, 230 von der Haar, F., 161 Von Niessen, W., 27 von Phillimborn. W.. 180 von Tigirstrom; R:, 153, 158, 168 Vorbruggen, H., 154 Vorkunova. E. L.. 263 Voskoboev; A. I.,’274 Vostretsova, N. L., 91, 114 Vostrowsky, O., 178, 180, 193 Vovski, B. A., 91 Vysotskii, V. I., 18 Waddington, T. C., 259 Wadsworth, W. S. jun., 119 Waechter, F., 162 Wager, J. S., 11, 89, 247 Wagner, A. J., 230 Wagner, K. G., 147. 160 Wagner, P. D., 167 Waheed, N., 67 Wakatsuka, H., 193 Wakefield, B. J., 72 Walach, P., 8

Author Index Walczyk, W., 228 Waldeck, S., 159 Walker, B. J., 4, 18, 183 Walker, J. B., 149 Walker, N. S., 34 Walker, R., 5 Walker, T., 83 Wallace, J. C., 133, 166 Wallenfils, K., 179 Walsh, C., 135 Walsh, E. J., 220, 226 Walsh, W. J., 225 Wanczek, K. P., 271 WanGk, W., 220,221 Wang, D. K. W., 17 Wang, T. Y., 274 Wannagat, U., 95,207 Warning, U., 14, 58, 93 Warnung, K., 70 Warren, C. D., 141 Warren, S., 79 Warren, W. A., 143 Wartell, R. M., 173 Washecheck, D. M., 82 Wasielewski, C., 89 Watanabe, M., 254 Watanate, Y., 105 Watari, F., 261 Wazeer, M. I. M., 35, 206 Wazer, J. R., 253 Webb, D. R., 175 Weber, A. L., 167 Weber, L. A., 174 Webster, D., 138 Webster, K., 237 Wechsberg, M., 275 Weedon, B. C. L., 20, 196 Weichmann, H., 7 Weidlein, J., 220 Weigel, L. O., 193 Weinberg, K. G., 8, 52 Weiner, M. A., 1 Weinmaier, J. H., 32,41,269 Weiss, R. G., 232 Weissbach, F., 128 Weith, H. L., 173 Welch, M. H., 147 Wells, R. D., 173 Wels, C. M., 182 Wenzel, H., 133, 164 Werner, D., 153, 224, 228 Westheimer, F. H., 35, 122, 139, 254 Westmijze, H., 8 Wetzel, R., 160 Whangbo, M.-H., 251 Wheaton, G. A., 186 Whistler, R. L., 139 White, J. E., 228 White, R. F. M., 251 White, T. M., 72 Whitesides, G. M., 104 Whitman, G. J. R., 139 Whittle, P. J., 34, 62 Widdowson, D. A., 17, 244 Wieczorek, M., 131, 268 Wiegand, G., 154 Wieland, T., 143

289 Wightman, R. H., 169, 199 Wihler, H.-D., 12, 68 Wilcox, C. F., 199 Wilde, R. L., 119 Wilkins, C. J., 82, 269 Williams, A., 131 Williams, F., 235, 237 Williams, J. K., 52 Williams, R. J. P., 176 Willmitzer, L., 147 Willms, L., 14, 69 Wilson, I. B., 144, 146 Wilson, J. D., 11, 89, 247 Wilson, K. E., 181 Wilson, N. H., 242 Winter, W., 9, 28, 232 Wiseman, J. R., 6, 73, 253 Witczak, M., 131, 268 Witkop, B., 172 Witkowski, J. T., 153 Witting, U., 274 Wittmann, H., 183 Wobke, B., 59 Wojtczak, L., 262 Wolcott, R. G., 143, 162 W2is R., 31, 41, 48, 49, 97, LJL

Wolf, W., 179, 185 Wolfe, J. F., 187 Wolfe. S.. 251 Wolfsberger, W., 216 Wong, S. S., 139, 160 Woodland, J. H. R., 219 Woods, M., 222,268 Worley, J. W., 84, 200 Worms, K. H., 102 Wortmann, J., 229 Wright, K., 29 Wright, P. W., 74 Wrixon, D., 134 Wu, R., 169, 173, 174, 175 Wunsch, G., 224,227, 228 Wurmb, R., 224,228 Wylie, V., 168 Wyrwicz, A. M., 176 Yakshin, V. V., 273 Yamada, M., 27 Yamada, S., 123 Yamamoto, H., 188 Yamamoto, K., 17 Yamamoto, Y., 184 Yamana, M., 16, 152, 245 Yamane, T., 249 Yamato, E., 13 Yamauchi, K., 124 Yamazaki, N., 99 Yang, H.-L., 163 Yastrebov, V., 254 Yates, K., 33 Yeagle, P. L., 142 Yokota, T., 159 Yolles, S., 219 Yoneda, N., 105 Yoneda, S., 110 Yonezawa, Y., 86, 233 Yoshida, H., 20, 186, 258

Yoshida, Y., 105 Yoshida, Z., 110 Yoshifuji, M., 234 Yoshimura, J., 86, 233 Yoskii, E., 105 Yotov, Y., 264 Younathan, E. S., 139 Yount, R. G., 167 Yow, H. Y., 51 Ysebaert, M., 173 Yudelevich, V. I., 88, 112 Yudina, K. S., 71 Yukhno, Yu. M., 112 Yurchenko, R. I., 219, 251, 265 Yurchenko, V. G., 21 1,219, 265 Yusupov, M. M., 97 Zagnibeda, D. M., 205,213 Zagorets, P. A., 52 Zagorskaya, T. V., 82 Zakharieva, M., 83 Zamaletdinova, G. U., 86 Zamojski, A., 15 Zaner, K., 249 Zappelli, P., 134 Zarytova, V. F., 170 Zasorina, V. A., 216 Zatko, D. A., 1 Zatorski, A., 201 Zatsepina, N. N., 273 Zavalishina. A. I.. 259 Zavlin, P. M.,270 Zbaida, S., 202 Zbiral, E., 24, 25, 189, 190, 218. 219 Zdorova, S. N., 97 Zeck, 0. F., 240 Zeiss, R., 256 Zelenetskii, S. N., 229 Zelinski, W. S., 105 Zemell, R. I., 140 Zhadanov, B. V., 273 Zhdanov, R. I., 168 Zhenodarova, S. M., 168 Zhidomirov, G. M., 258 Zhila, S. I., 102 Zhmurova, I. N., 64, 211, 216,219, 251,265 Ziehn. K.-D.. 70 Zimin, M. G:, 90, 91, 114 Zinich, J. A., 5 Zinkovskii, A. F., 88 Zinov’eva. L. I.. 124. 125 Zmudzka,’B., 172 ‘ Zon, G., 109 Zschunke, A., 250, 255 Zubay, G., 163 Zumwald, J. B., 195 Zwierzak. A.. 107 Zyablikova, Ti-.A,, 131, 259, 270 Zyk, N. V., 89 Zykova, L. Y., 183 Zykova, T. V. , 57, 66, 67, 110, 273