Organophosphorus Chemistry (SPR Organophosphorus Chemistry (RSC)) (v. 6)

A Specialist Periodical Report

Organophosphorus Chemistry Volume 6

A Review of the Literature Published between July 1973 and June 1974

Senior Reporter

S. Trippett, Department of Chemistry, University of Leicester Reporters

R. S. Davidson, Universify of Leicester

N. K. Hamer, University of Cambridge J . B. Hobbs, Max Planck lnstitut fur Experimentelle Medizin, W. Germany

D. W. Hutchinson, Universify of Warwick R. Keat, University of Glasgow J. A. Miller, University of Dundee

D. J. H. Smith, University of Leicester J. C. Tebby, North Staffordshire College of Technology

B. J . Walker, Queen’s Universify of Belfast

0Copyright 1975

The Chemical Society Burlington House, London W I V OBN

ISBN : 0 85186 056 7 Library of Congress Catalog Card No. 73-268317

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

Foreword

For the first time since the inception of this series there has been a noticeable fall in the volume of publication in organophosphorus chemistry in the year under review. While this may be due in part to the general recession in chemistry as a whole in the western world, it is also a reflection of the relative lack of significant advances in organophosphorus chemistry in recent years. The tremendous stimulus given by the Wittig olefin synthesis is now almost exhausted. Until the next major advance leads to an influx of new workers, the process of consolidation, particularly in the understanding of mechanism, continues, but at a lower level.

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

1

1 Phosphines 1 Preparation 1 From Halogenophosphines and Organometallic Reagents 1 From Metallated Phosphines 2 By Reduction 4 Miscellaneous 5 Reactions 6 Nucleophilic Attack on Carbon 6 Activated Olefins and Acetylenes 6 Carbonyls 7 Nucleophilic Attack at Halogen 9 12 Nucleophilic Attack at Other Atoms Miscellaneous 14 2 Phosphonium Salts Preparation Reactions Alkaline Hydrolysis Additions to Vinylphosphonium Salts Miscellaneous

16 16 19 19 21

3 Phospholes and Phosphorins

24

Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippeft

23

27

1 Introduction

27

2 Acyclic Systems

28

3 Three-membered Rings

30

4 Four-membered Rings

30

Contents

vi 5 Five-membered Rings Phospholans and Phospholens 173,2-Dioxaphospholans 1,3,2-Dioxaphospholens 172-Oxaphospholens 1,3,2-0xazaphospholans 1,3 5-Oxazaphospholens Miscellaneous

31 32 32 35 35 36 38 39

6 Six-co-ordinate Species

40

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

42

1 Halogenophosphines Physical and Theoretical Aspects Preparation Reactions Electrophilic Attack by Phosphorus Biphilic Reactions Miscellaneous Reactions

42

2 Silylphosphines and Related Compounds

52

3 Halogenophosphoranes

53

Physical and Theoretical Aspects Preparation Reactions

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

42 44 45 45 49 51

53 55 55

62

1 Preparation

62

2 Reactions

66

3 Physical and Structural Aspects

71

Contents

vii

Chapter 5 Tervalent Phosphorus Acids By B. J. Walker

74

1 Introduction

74

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

74 74 74 76 82 84 87 90 92 93 94

3 Phosphonous and Phosphinous Acids and their Derivatives

96

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

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

97

97 97 101 106 111

111 Synthetic Methods 114 Solvolyses of Phosphonic and Phosphinic Esters Reactions of Phosphonic and Phosphinic Acid Derivatives 118 Miscellaneous 121

Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson 124 1 Introduction

124

2 Coenzymes and Cofactors Nicotinamide Nucleotides Coenzyme A Pyridoxal Phosphoenolpyruvate

124 124 126 126 128

viii

Contents

3 Sugar Phosphates Synthesis Spectroscopic Properties

128 128 129

4 Phospholipids Isoprenoid Lipids Inositols

130 130 131

5 Biochemically Active Phosphonates Aminoethylphosphonate Phosphonomycin

133 133 133

6 Oxidative Phosphorylation

133

7 Enzymology Phosphoproteins Active Site Labelling Cholinesterases

135 135 135 136

8 Other Compounds of Biochemical Interest

137

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

141

1 Introduction

141

2 Mononucleotides Chemical Synthesis Cyclic Nucleotides AfEnity Chromatography

141 141 144 146

3 Nucleoside Polyphosphates Chemical Synthesis Enzymatic Synthesis Thiophosphates and Phosphoramidates Metal Complexes Other Polyphosphates

147 147 148 149 152 152

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

153 153 156 157

ix

Contents 5 Analytical Techniques and Physical Methods Molecular Weights Separation Structure Probes

Chapter 9 Ylides and Related Compounds By S. Trippett 1. Methylenephosphoranes

Preparation Reactions Carbonyls Mechanism Reaction at y-position of allylic ylides General Miscellaneous

158 158 158 159

160

160 160 160 160 160 161 163 167

2 Phosphoranes of Special Interest

170

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

173 173 174 176

4 Selected Applications of Phosphonate Carbanions

178

Chapter 10 Phosphazenes By R. Keat

182

1 Introduction

182

2 Synthesis of Acyclic Phosphazenes

182 182 184 185

From Amides and Phosphorus(v) Halides From Azides and Phosphorus(1n) Compounds Other Methods 3 Properties of Acyclic Phosphmenes Halogeno-derivatives Alkyl and Aryl Derivatives

188 188 189

4 Synthesis of Cyclic Phosphazenes

191

Contents

X

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

193 193 195 198 200

5 Polymeric Phosphazenes

202

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

202

Chapter 11 Photochemical, Radical, and Deoxygenation Reactions 204 By R. S. Davidson 1 Photochemical Reactions

204

2 Phosphinidene Oxides and Related Species

207

3 Radical Reactions

208

4 Deoxygenation Reactions Peroxides and Related Compounds N-Oxides and Nitro-compounds

216 216 217

5 Desulphurization Reactions

218

Chapter 12 Physical Methods By J. C. Tebby 1 Nuclear Magnetic Resonance Spectroscopy Chemical Shifts and Shielding Effects Phosphorus-31 (SP of PI11 compounds (SP of PIV compounds (SP of PV compounds Carbon-13 Fluorine-19 Hydrogen-1 Studies of Equilibria, Shift Reagents, and Solvent Effects Pseudorotation

221

221 221 221 221 222 224 224 225 225 225 227

xi

Contents

Restricted Rotation Inversion, Non-equivalence, and Configuration Spin-Spin Coupling JPPand JPM JPC

JPC,H JPCXH

JPXCH Relaxation Times, Paramagnetic Effects, and N.Q.R. Studies

228 229 229 230 231 232 234 235 236

2 Electron Spin Resonance Spectroscopy

238

3 Vibrational Spectroscopy

24 1 242 243

Stereochemical Aspects Studies of Bonding

4 Microwave Spectroscopy

246

5 Electronic Spectroscopy Absorption Photoelectron Fluorescence

246 246 248 248

6 Rotation and Refraction

249

7 Diffraction

249 249 252

X-Ray Electron 8 Dipole Moments, Conductance, and Polarography

253

9 Mass Spectrometry

255

10 pKa and Thermochemical Studies

256

11 Surface Properties (Chromatography)

25 7

Author Index

259

Abbreviations

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

Adenosine 5’-pyrophosphate bisazoisobutyronitrie adenosine 5’-phosphate Adenosine 5’4riphosphate 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-liquid chromatography hexamethylphosphoric triamide Nicotinamide-adenine dinucleotide Nicotinamide-adenine dinucleotide phosphate N-bromosuccinimide Nicotinamide mononucleotide nuclear quadrupole resonance inorganic pyrophosphate tetracyanoethylene tetrahydrofuran thin-layer chromatography Uridine 5’-pyrophosphate galactose Uridine 5’-pyrophosphate glucose

I Phosphines and Phosphonium Salts BY

D. J. H. SMITH

1 Phosphines Preparation.-From Halogenophosphine and Organometallic Reagents. An improved synthesis of trimethylphosphine from phosphorus trichloride and methyl-lithium at - 78 "Chas been described.l Another 'improved high yield' synthesis of the same phosphine uses the reaction of triphenyl phosphate with methylmagnesium iodide. Other trialkylphosphines have also been prepared by this latter method. Triarylphosphines with formyl or acetyl groups substituted into the aromatic rings can be prepared by a Grignard reaction using ethylene keta derivatives. The resulting phosphines (1) are treated with toluene-p-sulphonic acid. The acetyl derivatives may also be prepared by oxidation of the ethyl derivatives (2) followed by reduction with trichloro~ilane.~ Ph, -,PCI,

+ nBrMgC,H,--pCq

--+

Ph,-, P(C6H4-,CQ,

0

U P

O U O

R = Me, or H

n = 0,1,012 0

0

II

Ph,-nP(C, H4Et)n

KMno**

II

Ph,-,P(C,H,COMe),

HSiCI, f

Ph,_,P(C,H,COMe),,

A series of phosphines (3) containing alkenyl groups has been prepared by reaction of the chlorophosphine with the appropriate Grignard reagent.6 Tertiary arylethynylphosphines, e.g. (4), can be easily prepared by heating R. Markham. E. A. Dietz, and D. R. Martin, J . Inorg. Nuclear Chem., 1973, 35, 2659. W. Wolfsberger and H. Schmidbaur, Syn. React. Inorg. Metal-Org. Chem., 1974, 4, 149.

GLP. Schiemenz and H. Kaack, Annalen, 1973, 1480. G . P. Schiemenz and H. Kaack, Annalen, 1973, 1494. P. W. Clark, J. L. S. Curtis, P. E. Garron, and G. E. Hartwell, Canad.J. Chem., 1974,52, 1714.

1

2

Organophosphorus Chemistry

copper arylacetylides with the corresponding chlorophosphine in a polar aprotic solvent containing a lithium

Bu'PCl,

+ 2Me,SiCl +

2Mg

But P(SiMe,),

+ 2MgC1,

(5)

Organosilylphosphines, e.g. (3, are obtained directly from the reaction of chlorophosphines and trimethylchlorosilanes in the presence of magnesium. From Metalfated Phosphines. The preparations of a number of flexible aliphatic ligands, e.g. (6),containing the dimethylphosphino-group have been described, in which the sodium dimethylphosphide used was prepared from tetramethyldiphosphine. Me,P-PMe,

+ 2Na

-

2Me,PNa

ClCH,CH,CI +

Me,P(CH,),PMe,

(6 )

Me- - c)-.i ---Qpri

PPh,

(7)

'PPh,

(81

The chiral phosphines (7) and (8) have been obtained by the reaction of sodium diphenylphosphide with menthyl chloride and neomenthyl chloride, respectively.lo (Mercaptoalkyl)phenyIphosphines, e.g. (9) and (lo), may be prepared by treatment of chloro-thiols or episulphides with sodium phenylphosphide. The S-H is more acidic than the P-H in these compounds. B. I. Stepanov, L. I. Chekunina, and A. I. Bokanov, J. Gen. Chem. (U.S.S.R.), 1973,43, 2627. ' B. I. Stepanov, L. I. Chekunina, and A. I. Bokanov, U.S.S.R.P.370212 (Chem. A h . , 1973, 79, 53 572). H. Schumann and L. Rosch, Chem. Ber., 1974, 107, 854. G. Kordosky, B. R. Cook, and J. C. Cloyd, Inorg. Synth., 1973,14, 14. l o J. D. Morrison and W. F. Masler, J. Org. Chem., 1974, 39, 270. l1 K. Issleib and K. D. Franze. J. prakt. Chem., 1973, 315, 471 (Chem. Abs., 1973, 79, 78 892).

Phosphines and Phosphonium Salts

3

PhPHNa + CI(CH,),SH

PhPHNa +

--+PhPH(CH,),SH

apHp (91

0

--+

SH

(10)

Michael addition of sodium phosphides to alkenes containing nitro- or sulphonyl-groups gave the expected (2-nitroaIky1)- and (2-sulphonylalky1)phosphines. The reaction of potassium phenyl(trimethylsily1)phosphine with bromine or iodine in benzene gave pentaphenylpentaphospholan and the phosphine (11).13 This phosphine can also be obtained from dipotassium phenylphosphide, prepared by ring cleavage of pentaphenylpentaphospholan with potassium, and trimethyl~hlorosilane.~~ 10Ph(Me3Si)PK + 5X,

__f

(PhP),

+

5Ph(Me3Si),P

+ lOKX

(11) PhPK,

+ 2Me3SiC1

-+

PhP-PPh phi-kph

(11) j,

K

ii, CH,CI,

*

PhP-PPh I t PhPPPh

The phosphane (12) is ring-expanded by metallation and subsequent reaction with dichloromethane.l5 Dialkylphosphinobis(dimethylamino)methanes (13) are prepared from

/

( 1 3 ) R’ = MeorEt

(Me2N),CHOR2 + LiPR;

(14)

l4 l6

R2 = Me

K. Tssleib and P. von Malotki, J. prakt. Chem., 1973, 315, 463 (Chem. Abs., 1973, 79, 78 881). M. Baudler, M. Hallab, and A. Zarkadas, Chem. Ber., 1973, 106, 3962. M. Baudler and A. Zarkadas, Chem. Ber., 1973, 106, 3970. M. Baudler, J. Vesper, and H. Sandmann, 2. Naturjorsch., 1973, 28b, 224 (Chem. Abs., 1974, 80, 15 006).

4

Organophosphorus Chemistry

formamidinium salts or the ethers (14) by addition of lithium phosphides.16 Bis(dipheny1phosphino)amine (1 5) was the unexpected product from the reaction of 1,2,4,5-tetrabrornobenzene and sodium diphenylphosphide in liquid ammonia.l7 Ph,PNa

+

C,H,Br,

NH,

--

(Ph,P),NH (15) 5 5 %

(R'O),PH

+

RWl

Et,N

(R'O),P-PR:

(16) R' = Et, Bu,or Ph RZ = Pri or Ph

Alkylalkoxydiphosphines (1 6) are obtained by the addition of dialkoxyphosphines to dialkylchlorophosphines or, less satisfactorily, from the condensation of dialkoxychlorophosphines and dialkylphosphines in the presence of triethylamine.ls By Reduction. Phenylsilane reduces cyclic and acyclic phosphine oxides to the corresponding phosphines with complete retention of configuration and in high yields. l9 Phosphine oxides and phosphonium salts containing a t-butyl group can be reduced satisfactorily with lithium aluminium hydride, also with retention of configuration.2o The reduction of triphenylphosphine oxide with chlorodisilanes has been discussed.21 The synthesis of polyphosphines containing combinations of primary, secondary, and tertiary phosphorus atoms by the base-catalysed addition of P-H across the carbon-carbon double bond of vinyl phosphonates, followed by reduction with lithium aluminium hydride, has again been described.22The preparation of 1 ,Zbis(phosphino)ethane from the bis-phosphonate (1 7) by reduction with lithium aluminium hydride has been reported in (EtO),P + BrCH,CH,Br

+ (EtO),PCH,CH,P(OEt),

II

"

0

+

H,PCH,CH,PH,

0

(1 7 )

Methylated poly(tertiary)phosphines, e.g. (18), can be made by the base~ ~ protecting catalysed addition of P- H to vinylphosphine ~ u l p h i d e s .The sulphur atom(s) are removed by treatment with lithium aluminium hydride. M. Lischewski, K. Issleib, and H. Tille, J. Organometallic Chem., 1973, 54, 195. J. Ellermann and W. H. Gruber, 2. Naturforsch., 1973,28b, 310 (Chem. Abs., 1974, 80, 96 108). lB V. L. FOSS, Y . A. Veits, V. V. Kudinowa, A. A. Borisenko, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1973, 43, 994. l o K. L. Marsi, J. Org. Chem., 1974, 39, 265. l o R. Luckenbach, Phosphorus, 1973, 3, 77. I1 G. Deleris, J. Dunogues, and R. Calas, Bull. SOC.chim. France, 1974, 672. R. B. King, J. C. Cloyd, and P. N. Kapoor, J.C.S. Perkin I, 1973, 2226. 1a R. C. Taylor and D. B. Walters, Inorg. Synth., 1973, 14, 10. O1 R. B. King, J. C. Cloyd, and P. K. Hendrick, J . Amer. Chem. Soc., 1973, 95, 5083. l'

l7

5

Phosphines and Phosphonimn Salts

The desulphurization of diphosphine disulphides with tributylphosphine has been used to prepare tetramethyldiphosphine (19). Ph,PH + Me,PCH=CH,

I1 S

Me,P-PMe,

I1 II

--+ --+ Ph,PCH,CH,PMe,

(18)

+ 2Bu,P

MezP--PMe,

s s

+

2Bu,P=S

(19)

The effects of temperature and cathode material 25 and the use of aluminium electrodes26 on the electrolysis of phosphonium salts have been studied. Miscellaneous. Patent specifications have appeared for the convenient resolution of tertiary phosphines by complexation with the asymmetric palladium(rr) complex (20).

Carbonyl bis(dipheny1phosphide)(21), which is stable at room temperature, has been isolated 28 from the reaction of phosgene with diphenyl(trimethy1si1yl)phosphineat - 110 "C. Bis(trifluoromethyl)(trimethylsilyl)phosphine (22) has been prepared by an exchange reaction using bis(trifluoromethyl)phosphine.2 Fluoroalkylphosphines (23) may also be obtained by treatment of (fluoroalky1)iodophosphines with trifluoromethyl iodide in the presence of antimony powder.3o @

Me,SiPMe, + (CF,),PH

__f

Me,SiP(CF,),

+

Me,PH

(22 1

R,PI,,,

+ CF,I

--+

R,P(CF,),-,

(23) R = CF,or C3F, n = lor2 a6

*'

L. Horner, J. Roder, and D. Gammel, Phosphorus, 1973, 3, 175. P. Walach, D. H. Skaletz, and L. Horner, Phosphorus, 1973, 3, 183. S. Ootsuka and K. Tani, Jap. P., 56 628, 1973 (Chern. Abs., 1974, 80, 15 070). H. J. Becher and E. Langer, Angew. Chem. Internal. Edn., 1973, 12, 842. J. E. Byrne and C. R. RUSS,J. Inorg. Nuclear Chem., 1974, 36, 35. A. N. Laurent'ev, I. G. Maslennikov, and E. G. Sochilin, J. Gen. Chem. (U.S.S.R.), 1973,43, 2641.

Organophosphorus Chemistry

6

A convenient preparation of phosphine from the addition of aqueous sulphuric acid to aluminium phosphide has been described in detail.31 Reactions.-Niicleophilic Attack on Carbon. Activated olefins and acetylenes. The full paper describing addition of P-H bonds to vinyl isocyanides has been published.3 2 The reaction of diphenylphosphine with vinyl isocyanide in the presence of base proceeds normally, whereas the corresponding reaction with phenylphosphine gave the 1,3-azaphosphole(24). Ph,PH + CH,=CHNC

-+ Ph,PCH,CH,NC

PhPH, + CH,=CHNC

--+

I

Ph (24)

RPH,

+

PhCH=CHCOR

_ _ f

\

RP[CH(Ph)CH,COR], RPHCH,(Ph)CH, COR

The reactions of primary phosphines and the corresponding alkyl phosphides with ag-unsaturated ketones (25) have been discussed in some detaiL3" Tetrafluoroethylene with an excess of dimethylphosphine in the gas phase gives (26) by a reaction which is thought to be initiated by the bimolecular abstraction of a hydrogen atom from dimethylphosphine by tetrafluoroethylene.34Tetrafiuoroethylene also reacts with tetramethyldiphosphine by a radical process to give 1,2-bis(dimethylphosphino)tetrafluoroethane (27). C,F, + Me,PH -+ Me,P'

+ 'CF,CHF, -+

Me,PCF,CHF, (26)

C,F, + Me,PPMe,

Me,PCF,CF,PMe,

~ _ f .

(2 7) Tertiary phosphines have been shown to be very effective catalysts for Michael reactions. They appear to participate by nucleophilic addition to the activated 01efin.~~ The cyclic phosphine (28) has been prepared by a double Michael addition of phenylphosphine to 1-propenylcyclohexenyl ketone. a1 32

33

34 36

R. C. Marriott, J. D. Odom, and C. T. Sears, Inorg. Synth., 1973, 14, 1. R. B. King and A. E. Fraty, J.C.S. Perkin I, 1974, 1371. K. Issleib and P. Malotki, Phosphorus, 1973, 3, 141. R. Brandon, R. N. Haszeldine, and P. J. Robinson, J.C.S. Perkin If, 1973, 1295. R. Brandon, R. N. Haszeldine, and P.J. Robinson, J.C.S. Perkin If, 1973, 1301. D. A. White and M. M. Baker, Tetrahedron Letters, 1973, 3597. Y. Kashman and H. Ronen, Tetrahedron, 1973, 29, 4275.

Phosphines and Phosphonium Salts

7

Similarly, the dihydrophosphepin (29) can be obtained from cycloaddition of phenylphosphine and hexa-l,5-di~ne.~*

+ PhPH,

---+

I

Ph

Ph

(29)

Triphenylphosphine has been reported30 to react with TCNE at room temperature to give (30). Ph,P

+

(NC>$=C(CN),

4

Ph,P=C(CN), (3 0)

Carbotzyls. Several papers have appeared this year from Issleib’s group describing the synthesis of heterocyclic phosphorus compounds by acidcatalysed condensations of phosphines with carbonyl compounds. (Mercaptoalky1)phenylphosphines (31) react with aldehydes or ketones to form 1,3thiaphospholans40 or 1,3-thiapho~phorinans.~l The intermediate compound (32) can be isolated from a similar reaction with phenylisothiocyanate and is converted into a thiaphospholan by intramolecular loss of hydrogen sulphide.

+

PhPH(CH,),SH

R*CR2

II

_t

ph-d

0 (31) n = 2 o r 3

PhPH(CH,),SH

$.

R’ = H o r M e RZ = alkyl or Ph PhNCS -+ PhP(CSNHPh)CH,CH,SH (3 2)

38

41

-HzS+

PhP

f

G. Mark1 and G. Dannhart, Tetrahedron Letters, 1973, 1455. N. S. Zefirov and D. I. Makhon’kov, Zhur. org. Khim., 1973, 9, 851 (Clzem. Abs., 1973, 79, 5408).

40

,A

NPh

K. Issleib and H. J. Hannig, Phosphorus, 1973, 3, 113. K. Issleib and H. J. Hannig, 2. anorg. Chem., 1973, 402, 189.

8

Organophosphorus Chemistry

In similar reactions 1,3-azaphosphorinans4 2 and 1,3-azaphosphepans4s have been obtained from the condensation of aminophosphines (33) and carbonyl compounds. 1,2-Azaphospholans (34) are produced by oxidation of the aminophosphines with P~PH(CH,),NHR'

+

RZCR3

It

-

/(CH,)n, PW'

0 (33) R' = H,Et,or Ph n = 3or4

R2,R3 = H,Me,Ph

PhPH(CH,),NHR

-%-

)

Phb N '

I

R R = H, Et, or Ph

(34)

The addition of the (carboxymethy1)phosphine(35) to Schiff bases or semicarbazones44 gives 1,3-azaphospholan-5-0nes(36). PhPCH,CO,H

I H

f

Rt C=NR1

/ R3

-

(35) (36)

Bis(hydroxymethy1)phosphines catalyse the polymerization of phenylisocyanate. However, high yields of (37) are also obtained.46 RP(CH,OH), + PhNCO

RP(CH,O,CNHPh),

(37)

The addition of trimethylsilyl keten to diphenylphosphine results in the formation of the acyl phosphine (38) which is stable at room temperature but rearranges on heating.46

'a 44

H. Oehme and R. Thamm, J. prakt. Chem., 1973,315, 526 (Chem. Abs., 7 9 , 7 8 882). K. Issleib, H. Oehme, and K. Mohr, 2. Chem., 1973, 13, 139 (Chern. Abs., 1973, 79, 66 483). H. Oehme, K. Issleib, and E. Leissring, Phosphorus, 1973, 3, 159. R. K. Valetdinov, S. I. Zapirov, and M. K. Khasanov, J. Gen. Chem. (U.S.S.R.),1973, 43, 1021. A. S. Kostynk, N. T. Savel'eva, Yu. I. Baukov, and I. F. Lutsenko, Dakl. Vses. Konf. Khim. Atsetilena 4th, 1972, 2, 134 (Chem. Abs., 1973, 79, 78 890).

Phospkines and Phosphonium Salts

9

The reaction of germyl- or silyl-phosphines with biacetyl leadsQ7to cyclic products as well as acyclic derivatives derived from 1,l- and 1,Zaddition (see Scheme 1). Condensation of hydrometal-phosphines (39) with biacetyl gives mono-insertion products which cyclize in the presence of H,PtCl, into germaor sila-dioxolan derivatives. Et,P

Me,M(PEh),

+ MeC-CMe I1 II

PEt,O

I

--i)

1 1

Me,M-0-C-CMe Me

0 0

EhP

Me,M-PEt,

I H

+ MeC-CMe

II

0

II 0

-+

II

0

I II Me,M-0-C-CMe I I H

(3 9 )

Me

1

H,PtCI,

/o -c Me,M

‘0-

/Me

...

c,

+ Me,M

‘H

Scheme 1

Treatment of epoxides with lithium diphenylphosphide48 followed by oxidation gives p-hydroxydiphenylphosphine oxides which can be fragmented to olefins stereospecifically, thus constituting an olefin inversion (Scheme 2).

Scheme 2

Nucleophilic Attack at Halogen. Tertiary phosphine-carbontetrahalide adducts continue to be exploited for halogenation or dehydration reactions. Among those described this year is the addition of triphenylphosphine-carbon 47

C. Couret, J. Satge, J. Escudie, and F. Couret, J. Organometallic Chem., 1973, 57, 287. A. J. Bridges and G. H. Whitham, J.C.S. Chem. Comm., 1974, 142.

10

Organophosphorus Chemistry

tetrachloride to cholesterol or i-cholesterol to give a complex mixture of products which suggests 4 9 that both reactions are proceeding via an ion-pair (39a).

&

-+

products

OH

Aziridine can be obtained in good yields50 by the simultaneous action of triphenylphosphine, carbon tetrachloride, and triethylamine on N-substituted p-amino-alcohols(40). Ph,P + CCI, + HOCHR’

I H2CNHR2

Ph,P-0-CHR’

(40) R’ = H, Me, or Ph R2 = PhCH,, Ph, or But

N

I

RZ

A simple one-step preparation of cyclotriphosphazenes(41) and cyclotetraphosphazenes (42), which uses condensation of bis(dipheny1phosphine)amine

R. Aneja, A. P. Davies, and J. A. Knaggs, Tetrahedron Letters, 1974, 67. R. Appel and R. Kleinstiick, Chem. Ber., 1974, 107,5.

Phosphines and Phosphonium Salts

11

in the presence of carbon tetrachloride and triethylamine, has been described.51 Substituted ureas can be converted into chloroformamidines (43) by treatment with tertiary phosphinexarbon tetrachl~ride.~~

(43)

R', R2, R3 = alkyl, aryl

French workers prefer the use of tris(diniethy1amino)phosphine-carbon tetrachloride for reactions of this type. These reagents are used to substitute one hydroxy-group in 1,3-di0ls.~~ Heating the salt (44) gives the chloride directly, or the phosphine oxide may be displaced by added nucleophiles. Addition of sodium methoxide 54 gives the oxetans (45). The same reagents can be used to activate selectivelythe primary hydroxy-group of hexoses and hence allow it to be displaced by added nu~leophiles.~~ CI-I,OhNMe,),

Me, C(C HOH),

*

(Me2N)3P-CC*4 THF

/

c1-

Me$, 'CH,OH

(44)

/NaOMe

1 145

\

,CH,Cl Me2C'

CH,OH

'CH,OH

that benzoic acid may be conIn a similar reaction it has been verted into its anhydride by addition of tris(dimethy1amino)halogenophosphonium salts (46). +

PhC0,H

(Me,N),P-X

PhC0,H

~

r

PhCO,$(NMe,),

*

(PhCO),O

+

(Me,N),P = 0

PF,(46) X = C1,Br

Triphenylphosphine or tris(dimethy1amino)phosphine in aqueous solvents reduces benzyl aa'-dichlorobenzyl sulphoxide to a mixture of diastereomeric

hP Gs G4

65

6a

R. hppel and G. Salet, Cliem. Ber., 1973, 106, 3455. R. Appel, K. Warning, and K . D. Ziehn, Chem. Ber., 1974, 107, 698. B. Castro, M. Ly, and C. Selve, Tetrahedron Letters, 1973, 4455. B. Castro and C. Selve, Tetrahedron Letters, 1973, 4459. B. Castro, Y. Chapleur, and B. Gross, Bull. SOC.chirn. France, 1973, 3034. B. Castro and J. R . Dormay, Tetrcihedron Letters, 1973, 3243.

12

Organophosphorus Chemistry

benzyl a-chlorobenzyl sulpho~ides.~~ Full details of a kinetic study of the reduction of a-halogenobenzyl phenyl sulphoxides have been published. 68 The mechanism of the formation of betaines from the reaction of triphenylphosphine with pyrrolidine dione derivatives (47) has been

Cl

PPh,

(47)

R = Ph,PhCH,

Difluorocarbene can be generated8O by treatment of the phosphonium salt (48) with sodium methoxide or more conveniently by the reaction of tertiary phosphines with dihalogenodifluoromethane and potassium fluoride (Scheme 3). +

[Ph,PCF,Br]Br- + NaOMe

Ph,P + CF,X,

+ MF

X = Br,C1

M = K,Cs Scheme 3

Nucleophilic Attack at Other Atoms. A Lossen rearrangement occurs when aromatic hydroxamic acids are allowed to react with the triphenylphosphinediethyl azodicarboxylate complex in the presence of ethanol,61 to give the hydroxamates (49). ArCOKHOH + Ph,P + EtQ,CN=NCO,Et

ArCQNHOCQNHAr (49)

Attempted 1,3-dipolar additions of acetylenic phosphines to sodium azide gave only iminophosphoranes(50). No cyclic compounds were isolated.62The 67 68

O0

Oa

B. B. Jarvis and M. M. Evans, J . Org. Chem., 1974, 39, 643. B. B. Jarvis and J. C. Saukaitis, J . Amer. Chem. SOC.,1973, 95, 7708. D. Leyern, G. Morel, and A. Foucaud, Tetrahedron Letters, 1974, 955. D. J. Burton and D. G. Naae, J . Amer. Chem. SOC.,1973, 95, 8467. S . Bittner, S. Grinberg, and I. Kartoon, Tetrahedron Letters, 1974, 1965. V. A. Galishev, V. N. Chistokletov, A. A. Petrov, and L. A. Tamm, J. Gen. Chem. (U.S.S.R.),1973, 43, 1460.

Phosphines and Phosphonium Salts

13

formation of iminophosphoranesfrom reaction of diazocyclopentadienes (51) and triphenylphosphine continues to be studied.63 Ph,PC=CR'

f

R2N,

,C-CR'

Et$H C1' c'

php\

NR2

Solvent effects on the oxidation of triphenylphosphine by perbenzoic acid have been reported.6 4 The second-order rate constants are directly proportional to the dielectric constant of the solvent. Oxidation of methylphenylpropylphosphine with 3-chloroperbenzoic acid or ozone proceeds with retention of configuration.6 6 The reaction of alkyl- or aryl-phosphines with dialkyl peroxides or polyperoxides in aqueous solvents leads to the formation of alcohols or glycols, respectively. Desulphurization of p-keto-sulphides by tris(dimethy1amino)phosphine is thought to proceed via a phosphonium salt intermediate, e.g. (52), which cafl collapse to give a variety of products depending upon the substrate used and the reaction condition^.^^ 0

0

II

(Me,N),P+

I1

PhC 'CH-

PhCYSVPh I

Ph

I

Ph

PhCH S; (NMe, 1 (52)

0

II

0

+ PhC-Ph II

+ (Me,N),PS

p h c y P h Ph

Sulphimides (53) are reduced by the corresponding sulphides by triphenylphosphine in DMF.68 The kinetics of the reaction indicate that the initial a*

a6

Oe

B. H. Freeman, D. Lloyd, and M. I. C. Singer, Tetrahedron, 1974, 30, 211. S. A. Khan, N. Shakir, Z. Habib, and S. Begum, Pakistan J. Sci. Ind. Res., 1973,16,20 (Chem. Abs., 1974,80, 36 590). A. Skowronska, Bull. Acad. polon. Sci., Ser. Sci. chim., 1973, 21,459 (Chem. Abs., 1973, 79, 145 880). H. D. Holtz, P. W. Solomon, and J. E. Mahan, J . Org. Chem., 1973, 38, 3175. D. N. Harpp and S. M. Vines, J. Org. Chem., 1974, 39, 647. T. Aida, N. Furakawa, and S. Oae, Chem. Letters, 1973, 805 (Chem. Abs., 1973, 79, 104 481).

14

Organophosphorus Chemistry

reaction is nucleophilic attack by phosphorus at the sulphinyl sulphur atom. In the presence of alcohols a complex mixture of products is obtained 6 9 which, the authors claim, indicates the initial formation of a 1,3-dipole. The related reactions of sulphoxides and sulphimides with triphenylphosphine in the presence of p-tosyl isocyanate have also been Ph,P + R'S-NTs

I

DMF+

Ph,P=NTs

+ R'SPh

Ph (53) y o H PMR' + PhSR' + Ph,P=NTS

+ Ph,P-NHTs

It

0

Ts = O,SC,H,Me-p R1,R2 = PhCH,,.Me

ArS-NTs

I

+ Ph,P + TsNCO

_

~

Ph,P=NTs

f

+ Ph,PO + MeSAr + ArSO,NH,

Me Several tervalent phosphorus compounds readily remove selenium from triphenylmethyl isoselenocyanate (54) at room temperature forming the isocyanide quantitatively. Ph,CNCSe + R,P

-+

Ph,CNC + R,PSe

(54 1

Miscellurreous. The barriers to pyramidal inversion of a series of acyl phosphines ( 5 5 ) [RCOP(CHMe,),] have been measured. 7 2 Electron-withdrawing substituents in R facilitate the inversion whereas electron-donating groups hinder it because of the increase or decrease of interaction of the phosphorus lone-pair with the carbonyl group. The Hammett p constant for the inversion of phosphines has been determined using substituent constants derived from the inversion of 1-aryl-2,2-dimethylaziridines.73 The pyramidal inversion barriers for phosphines and arsines have been reviewed.7 4 Tertiary phosphines substituted at the a-carbon by electronegative groups, e.g. (56), react with boron trihalides to give products derived from carbonphosphorus bond cleavage.7 5 Phosphines containing only hydrocarbon groups do not react.

70

72

74 75

T. Aida, N. Furukawa, and S. Oae, Chem. Letters, 1974, 121 (Clrem. Abs., 1974, 80, 108 136). D. C. Garwood, M. R. Jones, and D. J. Cram, J. Amer. Chem. SOC.,1973, 95, 1925. L. J. Stangeland, T. Austad, and J. Songstad, Actu Chern. Scand., 1973, 27, 3919. R. G . Kostyanovskii, A. A. Fomichev, L. M. Zagurskaya, and K. S. Zakharov, Bull. Acad. Sci. U.S.S.R., 1973, 22, 1871. J. S. Splitter and M. Calvin, Tetrahedron Letters, 1973, 41 1 1 . K. Mislow, Trans. New York Acad. Sci., 1973, 35, 227 (Chem. Abs., 1973, 78, 158 447). K. C. Hansen, G. B. Solleder, and C. L. Holland, J. Org. Chem., 1974, 39, 267.

15

Phosphines and Phosphonium Salts

Triphenylphosphine reacts with styrene in the presence of palladium(rr) acetate to give trans-~tilbene.‘~

’”*

Ph,PCH,OCH, + BCl,

Ph,P(O)H

(56) Pd(OAc),

Ph,P + PhCH=CH,

*

Hxph

Ph

H

64%

Full details of the demethylation of the pentacyclic diether (57) with lithium diphenylphosphide have been published. Selective cleavage of the methoxy-group is achieved even when a four-fold excess of phosphide is present.

Me Ph,PLi

r”‘roEt

~

(5 7)

Calculations show that the hypothetical reaction of phosphine with acetylene to give (58; X = Ph) should be possible in the ground state whereas the reaction of ethylene with phosphine to give (58; X = PH,) requires a photochemically excited state.78

(58)

Various structural parameters and the conformation of biphosphine have been determined from the microwave spectra of biphosphine and deuteriated derivatives.’@ Rotational isomerism in tetramethyldiphosphine has been detected using photoelectron spectroscopy.8o The dipole moments of a series of methyl-substituted triarylphosphines have been measured.81 R. Asano, I. Moritani, Y.Fujiwara, and S. Teranishi, Bull. G e m . SOC.Jupaii, 1973, 46, 29 10.

R. E. Lreland, M. I. Dawson, S. C. Welch, A. Hagenbach, J. Bordner, and B. Trus, J . Amer. Chem. SOC.,1973, 95, 7829. 7 8 R . Vilceanu, Z . Simon, and A. Chiriac, Rco. Roumairie Chim., 1973, 18, 1353 (Clrern. A h . , 1973, 79,145 802). ’@ J. R. Durig, L. A. Carreira, and J. D. Odom, J. Amer. Chern. Soc,, 1974, 96, 2688. A. H. Cowley, M. J. S. Dewar, D. W. Goodman, and M. C. Padolina, J . Amer. Cliem.

77

SOC.,1974, 96,2648.

*’ I. P. Romm, N. A. Roznael’skaya, E. N. Gur’yanova, A. 1. Bokanov, and B. I. Stepanov, J . Gen. Cliem. (U.S.S.R.), 1973, 43, 1633.

Organophosphorus Chemistry

16

2 Phosphonium Salts Preparation.-The reaction of triphenylphosphine with l-bromoalkyl ketones has been describeds2in which the initially formed labile enolic salts (59) are converted irreversibly into phosphonium salts via ion-pairs (Scheme 4). When R is larger than ethyl the ion-pair is not formed and the enol salts decompose in the presence of atmospheric moisture to give alkyl aryl ketones. No en01 phosphonium salts are isolated from the reaction of bromo-diketones with triphenylphosphine in ether. The phosphonium salts (60) are precipitated directly.

Ph,gO

ph,P + O=C-CHBr

I 1

+

__f

A r R

Ar

RCH,C=O

I

Ar

Ph3$-O-C=CHR

I,

Br‘

‘I

RCH’C’--O

4.

-+.

Ph3P-CHRC=0

I

Ar

Ar 0

Br

C

CHR + Ph,P

I

It

As’

‘c’

-

0

II

0

Br-

-

Ph3i&RCOCO& Br(60)

Scheme 4

8-Bromo-B-nitrostyrenes undergo deoxygenation with triphenylphosphine in aprotic solvents to give high yields of cyanomethylphosphonium salts (61).s3 When this reaction is carried out in methanol the salts (62) are the products.84 Different products, thought to be derived from an azirine intermediate, are also obtained if electron-withdrawing substituents are present in the styrene aromatic nucleus. Cyanoethylphosphonium salts can be prepared by the addition of phosphines to acrylonitrile in the presence of a dialkylanilinium salt.ss The diuretic phosphonium salts (63) are obtained by cleavage of oxaphos-

88

M. I. Shevchuk, M. V. Khalaturnik, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.), 1973, 43, 756. C. J. Devlin and B. J. Walker, J.C.S. Perkin I, 1973, 1428. C. J. DevIin and B. J. Walker, J.C.S. Perkin I, 1974, 453. H. Teichmann, W. Thierfelder, and W. Kochmann, Ger. (East) P., 100 960 (Chem. A h . , 1974, 80, 83 236).

Phosphines and Phosphonium Salts ArCH=CBrNO,

+ 3Ph,P

17 __f

Ph,kHArCN + 2Ph,PO (61)

ArCH-CBrNO,

+ 3Ph,P

MeOH + Ph,kH,N=C(Ar)OMe

(62)

Ar

= Ph,4-MeC6H,

ArCH=CBrNO,

+ 3Ph,P

MeOH

+

Ph,P=CArCHO

+ + Ph,P=NPPh,

Ar = 3-N02C6H4 4-N02C,,Ha

pholes by dry hydrogen chloride in benzene.8sTreatment of trioctylphosphine with benzyl chlorides gives a series of salts which are anti-spasmodicand antiulcerogeni~.~~

Reaction of 7-chloronorbornadienewith triphenylphosphine in the presence of silver tetrafluoroborate gives the phosphonium salt (64)and a tricyclic salt (65) which is unstable at room temperature.88 iPh,

,6 & (64) 30%

(65)

PPh,

35%

A mixture of isomers of 7-chloro-7-methoxynorbornenegives an isomeric mixture of phosphonium salts (66) and (67) on reaction with triphenyl phosphine in liquid sulphur dioxide at -60 "C. Both salts can be converted into the non-classical dication (68). The salt (67) isomerizes to (66) at temperatures above - 14 0C.8g *a

*O

N. Soma, H. Takagi, I. Kawamoto, and K. Endo, Jap. P., 13 538/1973 (Chem. A h . , 1974, 80, 83 234). J. Diamond and K. Auyang, U.S.P. 3 742 064 (Chem. Abs., 1973,79, 53 546). P. Schipper and H. M. Buck, Phosphorus, 1973, 3, 133. P. Schipper, W. A. M. Castenmiller, J. W. DeHaan, and H. M. Buck, J.C.S. Chem. Comm., 1913, 574.

18

Organophosphorus Chemistry

The spiro-phosphonium salts (69) can be prepared by the reaction of the dilithio-derivatives (70) with triphenyl phosphate, followed by addition of sodium tetrafluorob~rate.~~

(69’)

Cyclopropyltriphenylphosphonium bromide is conveniently prepared from 3-bromopropyltriphenylphosphonium bromide (71) by treatment with equimolar sodium ethoxide in absolute ethanoLS1 +

Ph,PCH,CH,CH2Br (7 1)

--+Ph,P-Cq

Br-

Several a-(trisubstituted-stannyl)phenacyltriphenylphosphoniumsalts (72) have been isolated from the reaction of acylphosphoranes with chloro-tin compounds.y2

0e

R. Rothuis, J. J. H. M. Font Freide, and H. M. Buck, Rec. Trav. chim., 1973, 92, 1308. K. Utimoto, M. Tamura, and K. Sisido, Tetrahedron, 1973, 29, 1169. S. Kato, T. Kato, M. Mizuta, K. Itoh, and Y. Ishii, J. Organometaliic Chem., 1973, 51, 167.

19

Phosphines and Phosphonium Salts ,COh

Ph&-?HCOAr

+ R3SnC1 -+- ph3k€i

c1-

'SnR,

(72) R = MeorPh

The bis(dimethy1amino)phosphoniw-n cation (73) can be obtained by simply adding bis(dimethy1amino)chlorophosphine to aluminium chloride. The free energy of rotation about the P-N bond is 14.2kcal mol-1 clearly indicating a pn-pn P-N multiple bond.93 (Me,N),Xl + AlC&

MeZ?\ OoC>

+) P

A1CW

Me2Ny

(73) The primary product from the reaction of chlorodiphenylphosphine and benzaldehyde has been described 94 as a stable 1,4,2-dioxaphospholanium salt (74). Fh,PCl

f

+;I:-

2PhCHO --+ P h p

Ph (74)

Phosphetanium tetrachloroantimonates(75) can be isolated from the reaction of the corresponding dichlorophosphine and 2,4,4-trimethylpent-2-ene in the presence of aluminium chloride.95 WCl,

+ Me,C=CHCMe,

AIC1, 2CH,CL,

q i

Mcq

(75 1

Reactions.-Alkaline Hydrolysis. Ligand metathesis reactions of phosphines and phosphonium salts have been placed into monoligostatic and oligostatic reaction cycles.9s The alkaline hydrolysis of the phosphonium bromides (76) gives both furan and thiophen in a 1 : 3 molar ratio whereas the salt (77) gave 2-methylfuran and 2-methylthiophen in a 1.3 : 1 molar ratio.Q7 M. G. Thomas, R. W. Kopp, C. W. Schultz, and R. W. Parry, J. Amer. Chem. SOC., 1974,96,2646. O 4 N. J. De'Ath, J. A. Miller, and M. J. Nunn, Tetrahedron Letters, 1973, 5191. OLT S. E. Cremer, F. L. Weitl, F. R. Farr, P. W. Kremer, G. A. Gray, and H. Hwang, J. Org. Chem., 1973,38, 3199. R. Luckenbach, Tetrahedron Letters, 1974, 789. D. W. Allen, S. J. Grayson, I. Harness, B. G . Hutley, and I. W. Mowat, J.C.S. Perkin IZ, 1973, 1912. 2

20

Orgaizoplzosphorus Chemistry

The cleavage of acyclic phosphoiiium salts (78) with base, using homogeneous or heterogeneous conditions, with competing loss of the two aromatic ligands has been shown to proceed with some retention of config~ration.~~

The alkaline hydrolysis of various alkoxy(alky1thio)methylphenylphosphoniurn hexachloroantimonates (79) has been studied.ggThe nature of the product is affected by the nature of the substituent in the alkoxy grouping but is insensitive to substitution in the alkylthio-group. As expected cleavage of the alkoxy-group proceeds with inversion whereas retention of configuration at phosphorus is observed with loss of the alkylthio-group. The addition of methoxide ion to the related phosphonothiolate (80) has also been studied loo (see Chapter 6).

(79)

(80)

A detailed analysis of the stereochemistry of the alkaline hydrolysis of the cis- and trans-l-alkoxy-phosphctaniumsalts (81) has been carried out.lol The ability of the ligands X to undergo positional exchange from an equatorial position to an apical one in the intermediate phosphoranes was found to be in the order C1 E SMe > OPri > OEt, OMe > NMe2, which is due to the ability of the lone pairs of electrons in the heteroatom of the ligand to overlap with phosphorus as well as to the electronegativity of the ligand (see Chapter 2). The rate of hydrolysis of the phosphonium salt (82) is proportional lo the hydroxide ion concentration when the pH > 9. The change in rate with pH between pH’s 3 and 8 is ascribed to a change from rate-limiting hydration Q* Dg loo

lol

R. Luckenbach, Phosplzorus, 1973, 3, 117. I<. E. DeBruin and D. M. Johiison, J. Amer. Chem. SOC.,1973, 95, 4675. K. E. DeBruin and D. M. Johnson, J. Amer. Chem. Sac., 1973, 95, 7921. K. E. DeBruin, A. G. Padilla, and M. T. Campbell, J. Amer. Chem. SOC.,1973,95,4681.

21

Phosphines and Phosphonium Salts

around neutral pH to rate-limiting breakdown of the quinquecovalent intermediate in acidic so1ution.lo2 Me

II

";1----&OMe

+p/OMe

SbF;

'X

PF,'

(:81) X = Cl, SMe,OPri, OEt, OMe, or NMe,

'Ph

(82)

Alkaline hydrolysis of the spiro-phosphonium salt (83) gave the oxide (84) with no product derived from an expected Wittig-Stevens rearrangement.lO* Base-catalysed decomposition of the salts (85) gave varying amounts of ethylene and triphenylphosphine oxide.lo4

(84)

Ph,kH,CH, OR

OH+

Ph,PO

f

CH,=CH2

Br(85)

R

= Ph,4-NO,C6H4,

or C1CH2CH2

Solvent effects and the deuterium isotope effect of the alkaline hydrolysis of tetraphenylphosphonium chloride have been described.lo5 The reaction is strongly accelerated by increasing amounts of dioxan in the dioxan-water solvent. Additions to Vinylphosphonium Salts. Two reports of the reaction of amercaptoketones with triphenylvinylphosphoniurnbromide in the presence of base to yield 2,5-dihydrothiophens(86) have appeared.log#lo' R3

D. Gorenstein, J. Amer. Chem. SOC.,1973, 95, 8060. C. N. Robinson and R. C. Lewis, J. Heterocyclic Chem., 1973, 10, 395. l o 4 M. Zh. Ovakimyan, R. A. Khachatryan, and hl. G. Indzhikyan, Armyan. khim. Zhur., 1973, 26, 1051 (Chem. A h . , 1974, 80, 133 554). l o 6F. Y.Khalil and G. Aksnes, Acta Chem. Scnnd., 1973, 27, 3832. l o o J. M. McIntosh, H. B. Goodbrand, and G . M. Masse, J. Org. Chern., 1974, 39, 202. J. M. McIntosh and H. B. Goodbrand, Tetrahedron Letters, 1973, 3157. loo

loS

22

Organophosphorus Chemistry

Vinylphosphonium salts such as (87), which bear a leaving group in the /%position, can give, by reaction with acyloins in the presence of base, good yields of furans via the isolable 2-ethoxy-2,5-dihydroful'ans.lo* Ph (EtO)2CHCH2$Ph, + PhC-CHPh

NaH*

II OH I

Br:

()--oE~

ph 0

0

Ph

&p

h h o 0

(8 7)

The reaction of triphenylvinylphosphonium bromide with substituted diazoacetophenonesleads only to the formation of the 3-substitutedpyrazoles (88), as outlined in Scheme 5, presumably because of the high acidity of the 5-proton in the intermediate (89).lo9

I

Ar = Ph,MeC,H,, or NO,C,H,

0

II

Arc, Ph,kH,CH,;Ph,

4

Ph,kH==CH,

Ph,$HBr-

2Br-

+

9

'YN

H

(88)

Scheme 5

Triphenylvinylphosphonium bromide undergoes cycloaddition with a variety of dienes to give phosphonium salts, e.g. (90).l1O

(90)

Addition of sodium a i d e to arylethynyltriphenylphosphonium salts in DMF gives the phosphonium ylides (91) which can be hydrolysed to 1-H,2,3triazoles by aqueous base.lll M. E. Garst and T. A. Spencer, J. Org. Chem., 1974, 39, 584. E. E. Schweizer and C. S. Labaw, J. Org. Chem., 1973, 38, 3069. 110 R. A. Ruden and R. Bonjouklian, Tetrahedron Letters, 1974, 2095. ll1 Y.Tanaka and S. I. Miller, J. Org. Chern., 1973, 38, 2708. lo8

23

Phosphines and Phosphonium Salts +

ArC=CPPh,

OH'

+ NaN3 -+

~

X'

I

H

X

= CIorBr

At = ClC6H,orPh Miscellaneous. The phosphonium salt (92) has been shown to be an excellent reagent for the carboalkenylation of carbonyl compounds.ll* For example, the sodium enolate (93) and (92) give a cyclic product (94) which is thought to arise from a stabilized ylide by cyclization via an intramolecular Wittig reaction.

Et0,C

+ Ph,PO MenC02Me (94)

Chlorophenylphosphonium hexachloroantimonates (95) react with sodium azide in dichloromethane to give the corresponding azido-phosphonium salts.llS + nNaN,

Ph, -&!la

SbCI,'

-

Ph,

-nkN3),, SbCI;;

(95)

Peptide bonds can be formed with very little racemization by the use of the azido-phosphonium salt (96). The reagents are simply mixed in DMF at 0 OC. Acyl azides can also be obtained from the intermediate salt (97) by raising the temperature.ll4 1.r. studies on the interaction of phosphonium halides with carboxylic acids 112

11'

P. L. Fuchs, J. Amer. Chem. SOC.,1974, 96, 1607. W. Buder and A. Schmidt, Chem. Ber., 1973, 106, 3812. B. Castro and J. R. Dormoy, Bull. SOC.chim. France, 1973, 3359.

24

Organophosphorus Chemistry

R’CON,

R’CON HR2

+

I-

have been reported.llS The first stage of the reaction is the formation of a stable hydrogen bond between the carboxy-group and the halide ion, followed by displacement of the halide ion by the carboxylate anion. 1.r. spectroscopy has been used to show that the salts (98) exist as trans-enols whereas (99) exist in the dicarbonyl form.116Similarly, the acidity and tautomerism of diphosphacyclohexenone salts (100) have been described.ll

Ph,kH

,COR’

Phs

\c=.c

A 7

‘COR’

R’CO’ (98)

,OH

‘RZ

+/

CH +’\

Ph, kH(C0,E t)*

(99)

0 (100)

31PN.m.r. data of phosphonium salts do not reveal any electron delocalization through phosphorus.ll* 3 Phospholes and Phosphorins Electrophilescondense with the anion generated by treatment of the phosphole sulphide (101) with butyl-lithium either in the ring or at the methyl group depending upon the reagents used (Scheme 6).llB The chemistry of phosphorins and related compounds has been critically reviewed.120 The 4-monosubstituted phosphabenzene (102) has been obtained from the corresponding 1,4-dihydrostannin by reaction with phosphorus tribromide.121 Phosphorins having one carbon- and one oxygen-linked substituent on phosphorus may be made directly by the reaction of phosphorins (103) with diazo-alkanes in the presence of alcohols or phenols.122 I. E. Boldeskul, Y. P. Egorov, Y.P. Makovostskii, E. V. Ryl’tsev, and N. * G. Feshchenko, Teor. i eksp. Khim., 1973, 9, 350 (Chem. Abs., 1973, 79, 77 583). lie T. A. Mastryukova, I. M. Aladzheva, P. V. Petrovskii, E. I. Matrosov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1973, 43, 985. 11’ T. A. Mastryukova, Kh. A. Suerbaev, E. I. Matrosov, P. V. Petrovskii, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2593. 118 G. P. Schiemenz, Phosphorus, 1973, 3, 125. l l @ F. Mathey, Tetrahedron Letters, 1973, 3255. l a 0 K. Dimroth, Fortschr. Chem. Forsch., 1973, 38, 1. 111 G. Markl and F. Kneidd, Angew. Chem. Internat. Edn., 1973, 12, 931. P. Kieselack and K. Dimroth, Angew. Chern. Internat. Edn., 1974, 13, 148. 116

25

Phosphines and Phosphonium Salts

+ RZR3GNz Ph

Ph

(103) R’ = PhorPhCH, R2 = H or Ph R3 = H, Ph, or C0,Et

A

a

Ph ~

Ph

/’\ C H,R2, ~ ,

4

0

R4 = PhorMe

Electrophilic substitution reactions at C-4 of phosphorins have been described.la3For example (104) reacts with diazonium salts in the presence of water (Scheme 7), to give an azo-compound, which can be protonated on the b-nitrogen atom. In the presence of polarizable anions phosphinic acid derivatives (105) are formed. Anhydrous gold(1) chloride or iodide gave crystalline 1 : 1 complexes with 2,4,6-triphenylphosphabenzenein which the ring is attracted to gold via the lone-pair of electrons on the h e t e ~ 0 a t o m . l ~ ~ laa

I**

W. Schafer and K. Dimroth, Angew. Chem. Internat. Edn., 1973, 12, 753. K. C. Dash, J. Eberlein, and H. Schmidbaur, Synth. Inorg. Metal-org. Chemistry, 1973, 3, 375.

26

Organophosphorus Chemistry

Ph Me0

P MeO’ ‘OMe

OMe

NAr

,c1‘

Scheme 7

A comparative study of the photoelectron spectra of (106) and (107) indicates a similarity in the electronic effects produced by an spa hybridized carbon atom substituted by hydrogen and an sp2 phosphorus atom.12s

W. Schilfer, A. Schweig, F. Bickelhaupt, and H. Vermeer, Rec. Trau. chim., 1974,93,17.

2 Quinquecovalent Phosphorus Compounds BY S. TRIPPETT

1 Introduction

Oxyphosphorane chemistry has been reviewed,l with emphasis being placed on the importance of ligand sub-set symmetry in determining the relative stabilities of isomeric trigonal-bipyramidal phosphoranes, the effect being more pronounced for the equatorial than for the apical system. Applications of oxyphosphoranes in synthesis have also been reviewed.2 The spirophosphoranes (1 ;R = H or Me)3and (2; R = Me)* have been shown by X-ray analysis to be essentially square-pyramidal while (2 ;R = F) is distorted trigonal-bipyramidal. Although reflecting on the usual assumption

that quinquecovalent phosphoranes, both isolable and postulated as intermediates, will be trigonal-bipyramidal, these results also emphasize the small energy difference and fine balance between trigonal-bipyramidal and squarepyramidal geometries. Equally, there is a fine distinction between square pyramidal and 0" (2 3) geometries, and 'essentially square-pyramidal' could be read as 'essentially 0" (2 + 3)'. Doubtless these structures will refuel discussion on the precise pathways for the permutational isomerhations of phosphoranes. For an account of phosphoranyl radicals see Chapter 10.

+

a

a

F. Ramirez and I. Ugi, Bull. SOC.chim. France, 1974, 453. F. Ramirez, Synthesis, 1974, 90. J. A. Howard, D. R. Russell, and S. Trippett, J.C.S. Chem. Comm., 1973, 856. H. Wunderlich, D. Mootz, R. Schmutzler, and M. Wieber, 2.Nuturforsch., 1974,294 32.

27

28

Organophosphorus Chemistry 2 Acyclic Systems

Ab initio calculations on PF5 and on a variety of substituted fluorophosphoranes assign a significant role top,--d, bonding and support the BPR route for ligand exchange in PF5 and in PF,H,. The different ,JFPcoupling constants to apical and equatorial CF, groups allow the stable conformations at low temperatures of a variety of trifluoromethylphosphoranesto be established. This leads to ihe partial apicophilicity series F, CI>CF,>OSiMe,, OMe, SMe, NH,, H, Me. The phosphoranes (CF,),PH,, CF,PF,H, and (CF3),PF2Hhave been prepared by reduction of the corresponding fluorophosphoraneswith trimethylsilane in the vapour phase. The stable conformations at low temperatures of the first two are (3) and (4) CF-

F

F

respectively, in agreement with an order of apicophilicity F > CF, > H. The activation parameters for permutational isomerization in (4) and in PF3H2 have been determined through dynamic lH n.m.r. studies.* Dialkylaminosulphur trifluorides have been proposed as more convenient alternatives to SF, in the synthesis of difluorophosphoranesfrom phosphines and phosphine sulphides. The phosphoranes (5 ;X = 0 or S), obtained from difluorophosphine and alcohols or thiols,lowere stable only below 0 "C. Their n.m.r. spectra at - 60 "C showed them to be trigonal-bipyramidal with apical fluorines. HPFa + RXH + RXPFaHa (5)

Non-equivalent apical fluorines were observed l1in the low-temperature lBF n.m.r. spectra of the phosphoranes R1PF3(OR2)when the alkoxy-group was asymmetric, e.g. R2 = MeEtCH, ClCH,MeCH, etc. The effect was not due to slowing of rotation iound the equatorial P-0 bond as it was not observed in the phosphoranes RlaPF2(OR2). Ethyl benzenesulphenate (6) reacts with a variety of tervalent phosphorus compounds to give initially ethoxythiophenoxyphosphoranes(7), which can react with a second mole of (6) to give diethoxyphosphoranes and diphenyl a

A. Strick and A. Veillard, J . Amer. Chem. SOC.,1973, 95, 5574. R. G . Cavell, D. D. Poulin, K. I. The, and A. J. Tomlinson, J.C.S. Chem. Comm., 1974, 19.

J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1973, 813. J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1974, 15. L. N. Markovskij, V. E. Pashinnik, and A. V. Kirsanov, Synthesis, 1973, 787. l o L. F. Centofanti and R. W. Parry, Inorg. Chem., 1973,12, 1456. D. U. Robert, D. J. Costa, and J. G . Riess, J.C.S. Chem. Comm., 1973, 745.

29

Quinquecovalent Phosphorus Compounds ,OEt R,P + EtOSPh -+ R P (6) 'SPh (7)

R,P(OEt), + (PhS),

disulphide.l 2In some cases, e.g. starting with mixed alkylarylphosphines, the intermediates (7) decompose to give phosphine oxide and ethyl phenyl sulphitle. Alkoxytetra-alkylphosphoranes(8 ; R1 = Me or Et) react with alcohols to give distillable phosphonium salts containing the hydrogen-bonded anions (9; n := 1-3).13 The kinetics of the hydrolysis of penta-aryloxyphosphoranes

in 3 : 1 dimethoxyethane-water have been investigated l4 using stopped-flow techniques and interpreted in terms of six-co-ordinate intermediates or transition states. Full accountshave appeared of the use of dialkylaminotrimethylsilanes in the synthesisof dialkylaminofluorophosphoranes,l5 of the preparation and spectra of arninotetrafluorophosphorane,ls and of the X-ray analysis of the fluorophosphorane (lo).l7 The photoelectron spectra of aminophosphoranes are

consistent with preferled orientation in the equatorial plane of the lone pair on equatorial nitrogen.l* No evidence for slowing of rotation round the equatorial P-aryl bonds was found in the low-temperature 19F (-90 "C) or lI-3 (-80 "C)n.m.r. spectra of the difluorophosphoranes (11) and (l2).l9 la

la

l4

l6

l7 l8

L. L. Chang and D. B. Denney, J.C.S. Chem. Comm., 1974, 84. H. Schmidbauer and H. Stuhler, Chem. Ber., 1974, 107, 1420. W. C. Archie, jun. and F. H. Westheimer, J . Amer. Chem. SOC.,1973, 95, 5955. R. Schmutzler, J.C.S. Dalton, 1973, 2687. A. €I. Cowley and J. R. Schweiger, J. Amer. Chem. SOC.,1973, 95, 4179. W. S. Sheldrick, J.C.S. Dalton, 1973, 2301. A. H. Cowley, M. J. S. Dewar, D. W. Goodman, and J. R. Schweiger, J. Amer. Chem. SOC.,1973, 95, 6506. R. K. Oram and S. Trippett, J.C.S. Perkin I, 1973, 1300.

Organophosphorus Chemistry

30

3 Three-membered Rings The 1 : 1 adducts formed from phosphites and hexafluoroacetone wine, originally considered to be quinquecovalent phosphoranes containing phosphorus as part of a three-membered ring, have now been shown by X-ray analysis to be iminophosphoranes(13). 2o (RO),P + (CF,)2C=N-N=C(CF3)2

--+ (RO),P=N-C(CF,)2-N=C(CF,), (13)

A highly unstable phosphorane (16) is presumably an intermediate in the reaction of the phosphiran (14) with the dithieten (15) at -78 "C to give ethylene and the dithiophosphonite (17).21The reaction is stereospecific, cis-2,3-dideuteriophosphirangiving cis-1,2-dideuterioethylene.

4 Four-membered Rings

Details have appeared l@ of the preparation and variable-temperature l@F n.m.r. spectra of the phosphetan-hexafluoroacetone adducts (18). The transdimethylaminophosphorane (18; R = Me,N) on dissolving in hexafluoropropan-2-01 gave the hexafluoroisopropoxyphosphorane [18;

R = (CF,),CHO] as a pure isomer but it was not possible to determine the stereochemistry of this substitution. The spirophosphorane (20) was the only product from the reaction of the trans-l-benzylphosphetan(19) with hexafluoroacetone.In chloroformsolution in the presence of hexafluoropropan-2-01, equilibrium was established between (20) and its isomer (21). so

K. Burger, W. Thenn, J. Fehn, A. Gieren, and P. Narayanan, Chem. Ber., 1974, 107, 1526.

D. B. Denney and L. S. Shih, J. Amer. Chem. SOC.,1974,96,317.

Quinquecovalent Phosphorus Compounds

31

5 Five-membered Rings Strong e.s.r. evidence has been obtained 22 for the intermediacy of radicals in the formation of phosphoranes from tervalent phosphorus compounds and activated carbonyl compounds such as a-diketones, quinones, and a#?unsaturated ketones. The phosphinium radical reacts rapidly with a second molecule of the ketone as shown in the Scheme.

R,P

+ ' X

R,h*

+

ox 2

The barriers to permutational isomerizations in five-membered spirophosphoranes have been rationalized 2 s in terms of BPR processes involving diequatorial five-membered rings and preferred lone-pair orientations. The energy difference between (22) and (23) is composed of a general strain term due to the increased bond angle at phosphorus, the energy required to rotate the lone pairs on both X and Y from the preferred equatorial orientation to an G . Boekestein, W. G . Voncken, E. H. J. M. Jansen, and H. M. Buck, Rec. Truv. chim., 1974, 93, 69. S. Bone, S. Trippett, M. W. White, and P. J. Whittle, Tetrahedron Letters, 1974, 1795.

32

Organophosphorus Chemistry

apical plane, and the difference in apicophilicity between Y and R as determined from acyclic systems in which the lone pair on Y is free to take up its preferred orientation. Although conceived in terms of ideal trigonal bipyramids, there can be little doubt that phosphoranes such as (23) containing diequatorial small-membered rings will be considerably distorted, perhaps towards 0" (2 3) geometry. Phospholans and Phospholens.-Details have appeared 24 of the preparation and properties of homocubylphosphoranes, e.g. (24), and related compounds. An improved synthesis of (24)is as shown. A full account has been given 25 of the dynamic n.m.r. of the spirophosphoranes (25) in which the naphthyl

+

MeSO,F+

@/*

@$<

OMe OMe SO,F-

'Me

2 MeLi

WPMe3 (24) 44.5%

(25)

residues are, for steric reasons, confined to the equatorial plane. EquivaIence of the four methyls is achieved by Berry pseudorotation coupled to rotation round the P-naphthyl bond, and the barrier to this depends on the size of the substituent Y . 1,3,2-Dioxaphosph~Ians.-Triphenylphosphine and the 1,Zdioxetan (26) give 26 a high yield of the phosphorane (27), which decomposesat 55 "Cto give phosphine oxide and epoxide. The dihalogenophosphoranes (28) and (29) were obtained as s4

aE

E. W. Turnblom and T. J. Katz, J. Amer. Chem. SOC.,1973, 95,4292. D. Hellwinkel, W. Lindner, and H.-J. Wilfinger, Chem. Ber., 1974, 107, 1428. P. D. Bartlett, A. L. Baumstark, and M. E. Landis, J. Amer. Chem. SOC.,1973,95, 6486. V. N. Volkovitskii, I. L. Knunyants, and E. G. Bykhovskaya, Zhur. Vsesoyuz. Khirn. obshch. im. D . I. Mendeleeva, 1973, 18, 236 (Chem. Abs., 1973, 79, 42615).

33

Quinqueccvnlent Phosphorus Compounds

Pf

Ph,I’ + 0

Me ’Ie

Me

benzene 6”c

~

I’h3Pp$g:

550c* Ph3P0

‘ 0

Me

E:

+0

Me

The variable-temperature 19F n.m.r. of the diary1 phosphoramiditehexailuoroacetone adducts (30) have been interpreted2*in terms of a substantial difference in apicophilicity between aryloxy- and amino-groups, changing substituents on nitrogen having little effect. The variable-temperature lac,laF,and lH n.m.r. spectra of the caged polycyclic phosphorane (31) have now been studied down to - 165 0C.29 Permutational isomerization is still rapid at this temperature.

‘8

S. Trigpett and P. J. Whittle, J.C.S. Perkin I, 1973, 2302. Ramirez, I. Ugi, F. Lin, S. Pfohl, P. Hoffman, and D. Marquarding, Tetrahedron, 1974, 30, 371.

a @ F.

Organophosphorus Chemistry

34

Ph (34)

(32) + Me,C(OH)C(OH)Me,

-+

(35)

Quinquecovalent Phosphorus Compounds

35 Diniethylaminotetraoxyspirophosphoranesundergo methanolysis, either in refluxing benzene or chlorobenzene 30 or at room temperature in the presence of an equivalent of acid;31e.g. (32) gives (33). The use of 1,Zdiols leads to some interesting ring-exchange reactions. Thus (32) with pinacol gave the phosphorane ( 3 9 , also obtained from the tetraoxyphosphorane (36) and benzil. The benzoyloxyphosphorane (34) was obtained from (32) by treatment with two equivalents of benzoic acid, the reaction being reversed on addition of dimethylamine. 1,3,2-Dioxaphospholens.4-Trityl-o-benzoquinonehas been condensed with phosphites 3 2 to give pentaoxyphosphoranes. With tetrachloro-o-benzoquinone the chlorophosphine (37) gave an adduct formulated as (38).38 1 : 1 Adducts of hexafluorobiacetyl with trimethyl phosphite, the caged phosphite

(39)

F (RO),POP(:O)(OEt), + CFgOCOCF, (40) R = Me or Et

._)

3

C

0

0-P

/OR

I ‘OR ON:OMOEt),

(41)

(39),34and the anhydrides (40)35have been described. The adducts (41) are regarded as models of the hypothetical intermediate derived from addition of nucleophiles to the phosphorus of pyrophosphates such as ADP and ATP. Details have appeared 38 of the formation of cyclopropanes from arylidenemalononitriles and the biacetyl-trimethyl phosphite adduct. 1,2-Oxaphospholens.-Among ag-unsaturated ketones used in the formation of 1 : 1 adducts with tervalent phosphorus compounds are the sulphone (42) 37 so

aa a4

s8

D. Bernard and R. Burgada, Compt. rend., 1973, 277, C, 433. D. Bernard and R. Burgada, Tetrahedron Letters, 1973, 3455. M. M. Sidky and F. H. Osman, Tetrahedron, 1973, 29, 1725. M. Wieber and B. Eichhorn, Chem. Ber., 1973, 106, 2733. F. Ramirez, J. Marecek, I. Ugi, and D. Marquarding, Phosphorus, 1973, 3, 91. F. Rarnirez, Y. F. Chan, J. F. Marecek, and I. Ugi, J. Amer. Chem. SOC.,1974,96,2429. A. Foucaud and E. Corre, Bull. Soc. chim. France, 1973, 1574. B. A. Arbuzov, Y. V. Belkin, and N. A. Polezhaeva, Bull. Acad. Sci., U.S.S.R.,1973,22, 1062.

36

Organophosphorus Chemistry PhCH=C(SO, Ph)COPh (42)

Ph (PhCH= CH),CO

+ (MeO),P

loo

%

( M e O ) \ , P ~Ph= c H P h

and dibenzylideneacet~ne.~~ At 100 "Cthe latter with trimethyl phosphite gave the 2 : 1 adduct (43). Details have appeared3Dof the addition of phosphites to dibenzylidenecyclohexanone. Ethylene and o-phenylene ethylphosphonites react with but-3-en-2-one more rapidly than do the corresponding phenylpho~phonites,~~ and ethylene arylphosphonites react more rapidly than do o-phenylene arylphosphonite~.~~ The 1,2-oxaphospholens from trimethyl phosphite and but-3-en-2-one (44) and benzylideneacetylacetone (45) are powerful O-alkylating agents, converting acids and phenols into esters and ethers, re~pectively.~~ Mesitoic acid is esterified at room temperature. The mechanism is probably as shown in (46).

forty new spirophosphoranes containing a 1,3,2-oxaza-phospholan or -phospholen ring and a P-H bond have been prepared 4s and their equilibria with the conesponding tervalent phosphorus species studied. Symmetry is an important factor in determining the position of these equilibria. Further examples have been described of second-order asymmetric induction in the crystallization of spirophosphoranes derived

1,3,2-Oxazaphospholans.-About

a*

'l

B. A. Arbuzov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Izoest. Akad. Nauk S.S.S.R.,Ser. khim., 1973,2581. B. A. Arbuzov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Bull. Acud. Sci., U.S.S.R., 1972, 21, 2473. M. P. Gruk, N.A. Razumova, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.),1973,43,941. N. A. Razumova, M. P. Gruk, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1466.

W. G. Voncken and H. M. Buck, Rec. Trav. chim., 1974,93, 14. R. Burgada and C. Laurenco, J. Organometallic Chem., 1974,66, 255.

37

Quinquecovalent Phosphorus Compounds

from optically active /3-amino-al~ohols,~~ i.e. the crystallization of one pure isomer from a solution containing the two diastereoisomers (47)and (48) in equilibrium. The addition of a chiral shift reagent to solutions of (49) in deuteriated toluene caused splitting of the lH n.m.r. signals of (49) owing to the chirality of the spirophosphorane

(50)

t

:x-l

MeCH(0H)CONHMe + CP,

Me

Spirophosphoranes (50) containing a 4-keto-l,3,2-oxazaphospholanring have been prepared as shown.46In other cases, e.g. (51) and (52), only the tervalent form was obtained.

44 46

48

J.-F. Brazier, A. C. Carrelhas, A. Klaebe, and R. Wolf, Compt. rend., 1973,277, C,183. D. Houalla, M. Sanchez, and R. Wolf, Org. Magn. Resonance, 1973, 5, 451. C. Liurenco and R. Burgada, Compt. rend., 1974, 278, C, 291.

38

Organophosphorus Chemistry

The spirophosphorane (53) has now been obtained 47 in 48 % yield from triphenyl phosphite and o-aminophenol at 160-175 "C. It was previously postulated as an intermediate in the formation of (54) from o-aminophenol and tris(dialky1amino)phosphines and has now been shown48 to give (54) on heating with these phosphines.

H H (53)

(54)

1,3,5-Oxazaphospholens.-The nitrile ylides formed on thermal decomposition of the phosphoranes (55) have now been trapped49 with nitriles, with

(55)

dimethyl azodicarboxylate, and with carbonyl compounds such as benzaldehyde and ethyl pyruvate. slPn.m.r. evidence has been found for the formation of an unstable phosphorane, formulated as (57), in the reaction of trimethyl phosphite with the acylimine (56) at -40 "C.

47

48

4B

so

N. A. Tikhonina, V. A. Gilyarov, and M. I. Kabachnik, Bull. Acad. Sci., U.S.S.R., 1973, 22, 1393. M. A. Pudovik, S. A. Terent'eva, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.), 1973,43, 1838. K. Burger and K. Einhellig, Chem. Ber., 1973, 106, 3421. B. A. Arbuzov, N. A. Polezhaeva, and V. S. Vinogradova, Bull. Acad. Sci., U.S.S.R., 1973, 22, 1067.

39

Quinquecovalent Phosphorus Compounds

Miscellaneous.-N-AryI-N’-aroyldi-hides give the phosphoranes (58) with p h o s p h i t e ~ The . ~ ~ structure of an adduct with the caged phosphite (39) has been determined by X-ray analysis. It is a distorted trigonal bipyramid.

11

Spirophosphoranes (59) containing a 1,3,4,2-dioxazaphospholennucleus have been obtained from hydroxamic acids.62They are in equilibrium with the tervalent phosphorus species (60). Additional examples of spirophosphoranes derived from amidrazones have been described.63Unstable phosphoranes, e.g. (61), were obtained from cyclic chlorophosphites and o-phenylenediamine.5 3 They polymerized rapidly at

H (61) 31P + 64.4 p.p.m.

40 “C. ‘Thecompound formed from PF6 and the sulphur di-imide (62), previously thought to be a quinquecovalentphosphorane, has been shown 6 4 to be the irninophosphorane (63). s1

64

W. C . Hamilton, J. S. Ricci, jun., F. Ramirez, L. Kramer, and P. Stem, J. Amer. Chem. SOC.,1973, 95, 6335. A. Munoz, M. Koenig, R. Wolf, and F. Mathis, Compt. rend., 1973, 277, C, 121. Y.Charbonnel and J. Barrans, Compt. rend., 1973, 277, C, 571. R. Appel, I. Ruppert, R. Milker, and V. Bastien, Chem. Ber., 1974, 107,380.

40

Organophosphorus Chemistry

6 Six-co-ordinate Species Hydroxamic acids and the cyclic phosphoramidite (64) in the presence of triethylamine gave the salts (65).Sa The first six-co-ordinate phosphate anions (66) containing three different bidentate oxygen ligands were obtained as shown.6 5

[PNEt2

+ RCONHOH

Et,N

(64)

0

.=,,,-do) 1 \

0

(65)

6s

R = Me; 3’P+ 88 p.p.m.

M. Koenig, A. Munoz, D. Houalla, and R. Wolf, J.C.S. Chem. Comm., 1974, 182.

41

QuinquecovalentPhosphorus Compounds

Details have appeared 56 of the formation of six-co-ordinate species from o-phenylenephosphonites and catechol in the presence of triethylamine and of the remarkable properties of these salts. The formation of the phosphorane (68) in small yield from the reaction of the cyclic phosphoramidate (67) and

+

'O' Ph w

0""[a;)p NH2

%.-

H

2

(67) (68) 5 %

o-aminophenol in refluxing THF in the presence of triethylamine, and the formation in 37% yield of the salt (70) from the reaction of the cyclic phosphate (69) and catechol under the same conditions, are helds7 to be the first

+ (69)

0:: %* [

a

l

p

-

Et,kH

3 (70) 37%

direct evidence for the intermediacy of five-co-ordinate species in displacement reactions of five-membered cyclic phosphates.

68

I7

M. Wieber, K. Foroughi, and H. Klingl, Chem. Ber., 1974, 107, 639. T. Koizumi, Y.Watanabe, Y.Yoshida, and E. Yoshii, Tetrahedron Letters, 1974, 1075.

3 Halogenophosphines and Related Compounds BY J. A. MILLER

1 Halogenophosphines

This branch of organophosphorus chemistry continues to attract a great deal of effort, although the general pattern of the literature in recent years has been continued. Thus a number of significant theoretical papers have appeared, while experimental studies are clearly being devoted more to mechanistic than purely preparative chemistry. A comprehensivereview of the latter aspects of the subject has appeared.l Physical and Theoretical Aspects.-Perhaps the most interesting development of the year has been concerned with the varying levels of sophistication which have been applied to theoretical work on halogenophosphines. For example, extended Huckel calculations on cyanodiiluorophosphine (1) have been found2 to predict the observed non-linear P-C=N system. Using s- and porbitals only in the basis set, it was calculated that the cyanide group of (1) has a tilt of 9.4" (away from the fluorines), which compares favourably with the observed value of 8.8 k 0.8°.3 The same phosphine has been the subject of a semi-empirical SCF CND0/2 s t ~ d y and , ~ the results were compared with those obtaineds by ab initio

calculations. Although the former gives fair prediction of dipole and molecular structure, there are differences in atomic populations for both PF, and (1). Similar SCF CND0/2 calculations* with the isocyanate (2) also give geometric parameters in agreement with those determined by spectroscopy. In particular, these calculations predict the observed linearity of the isocyanate group in (2). Phosphorus trifluoride and pentafluoride have been studied by nonM. Fild and R. Schmutzler, in 'Organic Phosphorus Compounds', ed. G. M. Kosolapoff and L. Maier, Wiley-Interscience, New York, 1973, Vol. 4, p. 75. * C. Lejbovici, J . Mol. Structure, 1973, 18, 343. a P. L. Lee, K. Cohn, and R. H. Schwendeman, Inorg. Chem., 1972, 11, 1917. W. R. Hall and H. F. Hameka, Znorg. Chem., 1973,12, 1878. L. J. Aarons, M. F. Guest, M. B. Hall, and I. H. Hillier, J.C.S. Furaduy ZI, 1973,69,643. * B. M. Rode, W. Kosmus, and E. Nachbaur, Monatsh., 1974,105, 191. R. G . Hyde, J. B. Peel, and K. Terauds, J.C.S. Faruduy ZZ, 1973, 69, 1563.

42

43

Halogenophosphines and Re Iated Compounds

empirical methods, and the results compared both with experimental data and with predictions from more the-consuming MO SCF ab initio studies. Photoelectron spectra of a series of phosphines, including (3) and (4),have been reported,* and used to assess lone-pair effects on torsional barriers. It is Me,NP(Cl)CF,

(3) (4) (6) n = 2 found that the nitrogen ionization potentials remain relatively constant, whereas those found for the phosphorus lone-pairs vary with structure. The results are attributed* to a balance between steric effects and lone-pair repulsions. Photoelectron spectra of the phosphines ( 5 ) and (6) have been measured. The phosphines (7)'O and (8)-(lO)l1 have been studied by vibrational spectroscopy, and barriers to rotation (about C-P bonds) determined.

RE4 (7) R = Ph (8) R = CH,CI

EtP(C1)R (9) R = Et (10) R = Ph

Microwavespectra have been determined for methoxydifluorophosphine(11) l2 and methyldifluorophosphine (12),13and rotation barriers and dipole moments MeOPF, MePF, (1 1) measured. The determination of dipole moments from gas-phase heterodyne beat data has been reported1*for a range of difluorophosphines (13) and for dichlorofluorophosphine(14).

XPF, (13) X = CI,Br,orI

CAPF

Other physical aspects of halogenophosphines include a conformational study of the phosphetan (15),l5 and of the phosphines (16),lS from variable-

(15)

*

(16) n = 1,2, or 3

A. H. Cowley, M. J. S. Dewar, J. W. Gilje, D. W. Goodman, and J. R. Schweiger, J.C.S. Chem. Contm., 1974, 340. A. H. Cowley, M. J. S. Dewar, D. W. Goodman, and J. R. Schweiger, J. Amer. Chem. SOC.,1973,95,6506.

l1

A. B. Remizov and I. Ya. Kuramshin, Zhur. priklad Spektroskopii, 1974,20, 324B. A. B. Remizov, I. Ya. Kuramshin, and A. I. Fishman, Zhur. obshchei Khim., 1973,43, 1406.

E. G.Codding, C. E. Jones, and R. H. Schwendemann, Inorg. Chem., 1974,13,178. la E .G.Codding, R. A. Creswell, and R. H. Schwendemann, Znorg. Chem., 1974,13,856. I*

l4

J. G. Morse and R. W. Parry, J. Chem. Phys., 1972,57,5372.

la

R. P. Arshinova, A. N. Vereshchagin, and S. G. Vul'fson, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 2240. C. H.Bushweller and J. A. Brunelle, J. Amer. Chem. SOC.,1973,95,5949.

Organophosphorus Chemistry

44

temperature n.m.r. studies. The ion-molecule reactions of phosphorus trichloride have been studied,17 as has the ionization of (1) and phosphorus trifluoride under electron irnpact.l* An analysis of the 13C n.m.r. satellite spectrum of chlorovinylphosphinous dichloride has been published. Preparation.-A short review has appeared of the chemistry of dichloro(methy1)phosphine(17) and chlorodimethylphosphine(18), and the established, but not wholly satisfactory, preparations have been discussed. In a more recent paper, several minor, but significant, improvements are suggested 21 in two of the better known routes to (17)22and (18).23 @

MePCL,

Me,PC1

(1 7)

(18)

Improvement of old procedures is also the theme of a paper24 on the synthesis of trimethylphosphine (19), which was purified via its silver iodide 3MeLi+PCb

_t

Me,P

__f

[AgI,Me,PJ,

(20 1

(19)

complex (20). The preparation and reactions of chloro(chloromethy1)methylphosphine (21) have been reported.26 C!lCH,PCI,

+

MePCL,

3

MeCl

ClCH,P(Cl)Me < *IC1’ (21)

+

CH,Cf,

The NN-dimethylaminofluorophosphines(22) have been synthesized 26 by two routes, and bromochlorofluorophosphine (23) has been prepared as (Me,N),PF

(61

+ 2HX

-

Me,NPFX

f--

Me,NH

+ FPX,

(22) X = C1,Br HB*b =

c1

BrPClF (23)

shown. In the same paper, an extensive analysis of l0Fand 31P n.m.r. spectra of R. J. Mathews, Internat. J. Mass Spectrometry Ion Phys., 1974, 14, 75. P. W. Harland, D. W. H. Rankin, and J. C. J. Thynne, Internat. J. Mass Spectrometry Ion Phys., 1974, 13, 395. lD M. L. Sheer, Org. Magn. Resonance, 1974, 6, 85. g o H. Staendeke and H.-J. Kleiner, Angew. Chem. Internat. Edn., 1973, 12, 877. R. T. Markham, E. A. Dietz, and D. R. Martin, J. Inorg. Nuclear Chem., 1974,36, 503. G . W. Parshall, J. Inorg. Nuclear Chem., 1960, 12, 372. A. B. Burg and P. J. Slota, J. Amer. Chem. SOC.,1958, 80, 1107. R. T. Markham, E. A. Dietz, and D. R. Martin, J. Inorg. Nuclear Chem., 1973,35,2659. M. Wieber and B. Eichhorn, Chem. Ber., 1973,106,2733. R. G . Montemayor and R. W. Parry, Inorg. Chem., 1973,12, 2482. l7

45

Halogenophosphines and Related Compounds

u

0AN-SiMe,+PI,

-+

[

0E N ) P 1 3 - n (24) n = 1 or 2

(22) is presented.z6 The morpholinophosphines (24) ale the first substituted derivatives of phosphorus tri-iodide to be prepared, and, not surprisingly, are foundz7to be very air- and moisture-sensitive. The synthesis of the important chlorophospholan (25) has been improved,z8

CJI,=CH,

+ F2PPF2

-

(25 1

F,PCH,CH,PF, (26)

and (25) alkylated by Grignard reactions. New routes to the bisphosphine (26) have been and a study was made of complex formation with

(27) diborane. Lead tetraethyl has been used to prepare30 the phosphine (27) as outlined. Reactions.-Electrophilic Attack by Phosphorus. This year has seen a resurgence in Friedel-Crafts and related chemistry of the halogenophosphines, with the general objective of establishing mechanisms. For example, the conversion of phosphorus trichloride into complexes of either dichlorophenylphosphine (28) or chlorodiphenylphosphine(29) has been studied in order to establish the PhH + PCI, + AICl,

a PhPCl,, AlCl, (28)

n
PhJCl,AlCI,

(29)

kH ArPhPCl

experimental factors which control yield and product balance. Most critical is the reagent ratio, in particular the ratio PC13 : PhH, designated by n : 1 in the I7

A. M. Pinchuk, Zh. K. Gorbatenko, and N. G. Feshchenko, Zhur. obshchei Khirn.,

1973,43, 1855. B. Fell and H. Bearmann, Synthesis, 1974, 119. '' K. W. Morse and J. G. Morse, J. Amer. Chem. SOC.,1973, 95, 8469. a O V. K. Khairullin and R. Z. Aliev, Zhur. obshchei Khim., 1973, 43, 1921. 81 K. A. Petrov and G. Ya. Legin, Zhur. obshchei Khim., 1973, 43, 37.

46

Organophosphorus Chemistry

scheme shown. Addition of a different hydrocarbon to the complex of (28) provides a route to mixed diarylphosphinous derivatives.31 A similar treatment 32 of the ethylene-phosphorus tribromide reaction has been published. When aluminium tribromide is used as catalyst, the AlBr, : PBr, ratio is important, and determines whether the product is the dibromophosphine (30) (ratio 1 : 320), or whether the complex (31) predominates PBr, + AIBr,

-

Br,;

-

BrCH,CH,PBr,, AlBr,

CH,=CH,

J

ll

\

CH,=CH2

0 (BrCH,CH,),POR

...B r h r ,

i, Nter u, ROH

(BrCH,CH,),$Br,, ilBr,

BrCH, CH,PBr, (30)

(31)

(ratio 1 : 6). The complex (31) is found to yield bis-(2-bromoethyl)phosphinic acid derivatives as shown. The related reaction of ethylene with phosphorus trichloride in the presence of aluminium halides has had a chequered history. The original paper on this route to P-C bonds made no mention of the use of ethylene as olehic Subsequently, Russian workers reported 34 the isolation of the phosphines (32) and (33) from ethylene-phosphorus trichloride reactions, CH,=CH,

+ PCI,

m3b

ClCH,CH,PCl, + complex

-#-k

(33)

8 II

(ClCH, CH,),PCl

ClCH,CH,P(OH),

(33)

(34)

+ 0

II

(ClCH,CH,), POH (35)

although this work was claimed36to be unreproducible. A further study3sof the reaction has now confirmed the formation of (32), and described the isolaR. I. Pyrkin, Ya. A. Levin, and E. I. Gol'dfarb, Zhur. obshchei Khim., 1973, 43, 1705. E. Jungermann, J. J. McBride, R. Clutter, and A. Mais, J. Org. Chem., 1962, 27, 606. I b A. I. Titov, M. V. Sizova, and P. 0. Gitel', Doklady Akad. Nauk S.S.S.R., 1964, 159, I*

385. L. Maier, Helu. Chim. Acta, 1969, 52, 1337.

I6

** Ya. A. Levin and R. I. Pyrkin, Zhur. obshchei Khim., 1973,43, 77.

47

Halogenophosphines and Related Compounds

tion of a complex, which on work-up yielded the acids (34)and (35), [although the latter was not formed via a complex of (33)] but did not give any (33). The authors36have come to the conclusion that small experimental differences, such as the state of the aluminium chloride, are responsible for the confusion! The addition of phosphorus trichloride to olefins in the presence of perchloryl fluoride (36) has been further 38 The olefinic component of

(37) X = ForCl

the reactants seems to be limited to simple acyclic and cyclic o l e h (ethylene 37 or cycIohexenea8)and the products have the general structure (37). Two papers have been devoted3e~Po to stereochemical aspects of the synthesis of phosphetans from 2,4,4-trimethylpent-2-ene (38). The stereochemistry of the reaction of (38) with dichlorophosphines is determined8eby RPCI,

(R =

+

Me, Ph, Cl)

(38)

stereomutation (R = Me,Ph)

)$<;

isomeric oxides

C1

the mode of quenching of the intermediate complexes (39) with water. The complexes (39) are shown to consist of two isomers, which may be interconverted by chloride ion (present in the aqueous quenching medium), presumably via phosphorane intermediates. The synthesis and reactions 40 of (40) have been described, a detailed discussion being devoted to stereochemical aspects of its reactions.

* @

40

S. V. Fridland, N. V. Dmitrieva, I. V. Vigalok, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 1494. S. V. Fridland, N. V. Dmitrieva, I. V. Vigalok, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 572. S. E. Cremer, F. L. Weitl, F. R. Farr, P. W. Kremer, G. A. Gray, and H. 0. Hwang, J. Org. Chem., 1973, 38, 3199. J. Emsley, T. B. Middleton, and J. K. Williams, J.C.S. Dalton, 1973, 2701.

Organophosphorus Chemistry

48

(40)

The reaction 41 of phosphorus trihalides with lY3-dienesand phosphorus pentasulphide leads to a one-step synthesis of the phospholens (41) and (42).

(41)

(42)

Both phospholens are usually formed, except for the case of 2,3-dimethylbuta1,3-dieneYwhich gives only the A3-phospholen.41 Intermediate acetoxychlorophosphines (43) have been detected 4 2 * 43 when the reaction between acetic anhydride and the phosphines (7) and (44)are carried out below 50 "C. The phosphines (43) have also been trapped by reaction with a-halogeno-ethers, as shown. It would appear that these reactions of (7) and (44)involve electrophilic phosphorus, whereas the corresponding reactions of dialkylchlorophosphines, such as (45),44 are more complex mechanistically, and lead to quite different products. 0 (MeCO),O + R'PCI,

<

i

It

R'P(C1)OCMe + AcCl

(7) R' = Ph (44) R' = Et 0

II , PCH (0Ra)Me c1 R'\

(MeCO),O + Et,PCl --+

Ail

Et,PC(OCMe)--CH,

(45) B. A. Arbuzov, V. K. Krupnov, and A. 0.Vizel, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 1176. M. B. Gazizov, D. B. Sultanova, A. I. Razumov, L. P. Ostanina, and A. A. Galyautdinova, Zhur. obshchei Khim., 1973, 43, 213. M. B. Gazizov, D. B. Sultanova, A. I. Razumov, L. P. Ostanina, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 2160. V. S. Tsivunin, Yu. N. Afanas'ev, R. G. Ivanova, T. A. Zyablikova, and G. Kh. Kamai, Zhur. obshchei Khim., 1968, 38, 1523.

49

Halogenophosphines and Related Compounds

The ring-opening reactions of oxetans by phosphorus trichloride have been further studied, and the effects of changing reagent ratios assessed;4s the pathway to the esters (46)is outlined below. Chlorodi-isopropylphosphine (47) PC1, + 2

q

-+ ClP(OCHMeCH,CH,Cl),

Me

oxctan

P(OCHMeCH,CH,Cl), 0

4

ClCH,CH,CHMeOP (46)

+ ClCH,CH,CHMeCI

reacts 4Eiwith dibutyl phosphonite as shown; the same product was unexpectedly formed by oxidation of the phosphine (48). 0

I1 PrfPCl + HP(OBU),

0

I1

base, PrfPP(OBu), sHB0 PrjPP(OBu), (48)

(47)

The reactions of phosphorus trichloride with gly~erol,~' and of phosphorus tribromide with the 2-bromocyclohexanols,48have been investigated. Biphilic Reactions. Reactions between carbonyl compounds and halogenophosphines continue to be prominent in the literature. Thus hexafluoroacetone has been converted into halogenophosphoranes by reaction with (45),49chlorodi-n-propylphosphine(49),4D or 1-chloro-2,2,3,4,4-pentamethylphosphetan (50).60By contrast, the analogous reactions of benzaldehyde with

0

I1

2F,CCCF, + R,PCl (45) R = Et (49) R = Pr

'?

4s

B. A. Arbuzov, 0. N. Nuretdinova, L. Z. Nikonova, and E. I. Gol'dfarb, Izoest. Akad. Nauk S.S.S.R., Ser. khirn., 1973, 627. Yu. A. Veits, A. A. Borisenko, V. L. FOSS,and I. F. Lutsenko, Zhur. obshchei Khim., 1973, 43, 440. N. A. Makarov, E. T. Mukmenev, and B. A. Arbuzov, Doklacly Akad. Nauk S.S.S.R., 1973, 213, 1331. G. Bellucci, G. Ingrosso, F. Marioni, A. Marsili, and I. Morelli, Gazzetta, 1974,104, 69. V. N. Volkovitskii, I. L. Knunyants, and E. G. Bykhovskaya, Zhur. Vsesoyuz. Khim. obshch. im. D. I. Mendeleeva, 1973, 18, 112. R. K, Oram and S. Trippett, J.C.S. Perkin I, 1973, 1300.

Organophosphorus Chemistry

50

-x-

F3C CF,

chlorodiphenylphosphine(29), or the phosphetan (51), appear to give phospholanium saltsY6lalthough these structures would be expected to be more strained than the correspondingphosphoranes. Taken together, these reactions establish that formation of 1,3,2- and 1,4,2-dioxaphosphoranesyor the related phospholanium salts, from carbonyl compounds is not restricted to tervdent phosphorus esters and a i d e s 6 *Further reactions of these products, and their relationship to phosphineoxides, are discussed below in the section on Halogenophosphoranes, and in the chapter on Phosphine Oxides (Chapter 4). The phosphine (27) reacts as shown with chloralSO and with substituted

iiilil S

PCHRCH,CO,Me

I

4

i. RCH=CHCO,H u, McOH

Et

Et ‘I

N.J. De’Ath, J. A. Miller, and M.J. Nunn, Terrahedron Letters, 1973, 5191. P. Ramirez, Accounts Chern. Res., 1968, 1, 167.

51

Halogenophosphines and Related Compounds

(53) acrylic The hindered propargyl alcohol (52) reacts 5 4 with phosphorus tribromide to form the novel ester (53), and the mechanism of the reaction has been discussed. Difluorophosphine (54) and alcohols form phosphoranes F ROH + F,PH (54)

_+_

RO-P’,

I3

I H

F

(55 1

(55),55the chemistry of which is discussed below in the section on Halogeno-

phosphoranes. Exchange reactions of substituents attached to phosphines are well known, but the principles that govern either the kinetic or thermodynamic aspects of scrambling are not well defined. Two attemptss6S5?have been made to document such exchanges, and they are noteworthy for their clear distinction between rate and equilibrium data. In one of these papers,66the exchange of halogens between MeP, MeP(O), MeP(S), and MGSi centres is described, and the results show a clear dependence upon the other ligand attached to the central atom. A similar approach to the exchange of ligands between the phosphorus centres (56) and (57) is described in the second paper.67 0

MePXY (56)

II + MePXY

0

I1

MePX, + MePY,

(57)

Miscellaneous Reactions. The complexes between halogenophosphines and boron halides have been investigated for a range of reactants. For example, dichloro(methy1)phosphine (17) forms 1 : 1 adducts with all the boron halides except the trifluoride,68a result confirmed by another group.21With boron tribromide or tri-iodide, halogen exchange is observed.68The second paper 21 reports that complex stability follows the order of basicity Me3P> MqPCl> MePCl, > PCI,. The formation and breakdown of phosphoranyl radicals (58) 69 64

65

6e 67 6*

V. K. Khairullin and R. 2. Aliev, Zhur. obshchei Khim.,1973, 43, 2165. R . C. Elder, L. R. Florian, E. R. Kennedy, and R. S. Macomber, J. Org. Chem., 1973, 38, 4177. L. F. Centofanti and R. W. Parry, Znorg. Chem., 1973, 12, 1456. K. Moedritzer and 3. R. Van Wazer, Znorg. Chem., 1973, 12, 2856. K. Moedritzer, Phosphorus, 1973, 2, 179. R. M. Kren, M. A. Mathur, and H. H. Sisler, Inorg. Chem., 1974, 13, 174.

3

Organophosphorus Chemistry

52 MeFCl, + BX,

X = cT,Br,I

: MePCl,,BX,

(17) R,PCl,-,

+ Bu'O'

-+

R,~CI,-,(OBU~) (58)

J

0 II

X* + ButOPRnX2+,

But' + Rn+X3-,, by interaction of various halogenophosphines with t-butoxyl radicals are described.69

2 Silylphosphines and Related Compounds Several syntheses of trimethylsilylphosphineshave been described. Thus the silylphosphines (59) have been prepared O0 by a Grignard-type reaction. Me,SiCl

i' Mg ii, Ram+

Me,SiPR,

*

Me,MPR,

(59)

(60)

R = C1 or But M = Ge or Sn Treatment of (59) with halides of the higher Group IV elements leads 6o to the analogous phosphines (60). Phosphides continue to be of use in the preparation PhPK,

+ 2Me3SiC1

(Me,Si),PPh (61)

of silylphosphines, as with (61).61A similar route to silylphosphineshas been used in the synthesis of the potential bis-ligands (62) and (63).62 ClCH,SiMe,Cl + Me,PLi Me,PCH,SiMe,PMe, (62) Me,NCH,SiMe,NMe,

i. PCI, ii,Me,pfi+

Me,NCH, SiMe, PMe,

(63)

Silylphosphineshave been applied to the synthesis of other phosphines and that of silanes containing no phosphorus. For example, the bisphosphine (64)

c1 "$0

0

+ 2Ph,PSiMe, (59)

ph2p)40

Ph,P

(64 1 I*

D. Griller and B. P. Roberts, J.C.S. Perkin ZZ, 1973, 1339. H.Schumann and L. Rosch, Chem. Ber., 1974,107, 854. M.Baudler and A. Zarkadas, Chem. Ber., 1973, 106, 3970. J. Grobe and G. Heyer, J. Orgammetallic Chem., 1973,61, 133.

0

53

Halogenophosphines and Related Compounds

looks like a potentially useful ligand, and its synthesis from (59) has been reported.63The anion of phenyl(trimethylsily1)phosphine has been used to

prepare (61) and (65). The acylphosphines (66)65and (6ng6have been prepared from (59) by reaction with acetyl chloride and phosgene, respectively. Treatment of silylphosphine (68) with amines in the gas phase givesg7 quantitative yields of silylamines. Pyrolysis of (68) (using deuterium labelling) H3SiNR, (R = Meor Et) I H,SiPH,

HCNO

*-

H,SiNCO

(68) pyrolysis

H,Si + [PHI (69)

H,Si

+ PH,

has provided evidencess for the pathways outlined, including the first generation of phosphylene (69). The molecular structure of trifluorosilylphosphine (70) has been studied.sD

3 Halogenophosphoranes Physical and Theoretical Aspects.-Phosphorus pentafluoride continues to attract attention from those interested in theoretical aspects of structure, and from those more inclined to test the predictions of others. The most detailed ub initio calculations 70 of the year lead to confirmation of Berry pseudorotation @a

'7

as

D. Fenske and H. J. Becher, Chem. Ber., 1974,107, 117. M. Baudler, M. Hallab, A. Zarkadas, and E. Tolls, Chem. Ber., 1973, 106, 3962. H. J. Becher, D. Fenske, and E. Langer, Chem. Ber., 1973,106, 177. H. J. Becher and E. Langer, Angew. Chem. Internat. Edn., 1973, 12, 842. C. Glidewell, Inorg. Nuclear Chem. Letters, 1974, 10, 39. L. E. Elliott, P. Estacio, and M. A. Ring, Inorg. Chem., 1973, 12, 2193. R. Demuth and H. Oberhammer, 2.Nuturforsch., 1973, 28a, 1862. A. Strich and A. Veillard. J. Amer. Chem. SOC.,1973, 95, 5574.

Organophosphorus Chemistry

54

as the likely permutational mechanism, and to confirmation of the prediction 71 that equatorial n-donors will have the donor orbitals in the equatorial plane. This work 70 also leads to estimates of phosphorus d-orbital participation in bonding, and of the energetic consequencesof placing groups such as -SH or -NH, in the equatorial, as opposed to axial, positions. On the experimental side, phosphorus pentafluoride has been investigated, and photoelectron Raman 7 4 and gas-phase recoil studies 75 have been reported. The conformational preference of n-donors in phosphoranes has also been discussedgin a paper on the photoelectron spectra of the phosphoranes (71). An X-ray analysis of the phosphorane (72) shows 7 6

(71) n = 1,2,or 3

(72)

the pyrrole ring to lie in an axial plane of the trigonal bipyramid. Fluorine and chlorine are placed at the top of the apicophilicity table determined 7 7 from low-temperature n.m.r. studies of trifluoromethylphosphoranes (see Chapter 2 for details). The phosphoranes (73) show 7 8 diastereotopic axial fluorines when the F,P(OR)R (73 1

alkoxy-group bears a chiral carbon. If the alkoxy-group is achiral, then the axial fluorines become equivalent. N.m.r. studies of the fluxional phosphoranes (74) have been and variable-temperature data analysed to give activation parameters for intramolecular exchange. F,PHR

(74) R = HorCF,

The 31Pn.m.r. shifts of a range of fluorophosphoraneshave been reported.80 Other physical aspects of halogenophosphoranes include the U.V. spectra of phosphorus pentafluoride-ether complexes,81 n.q.r. spectra of the R. Hoffmann, J. M. Howell, and E. L. Muetterties, J. Amer. Chem. Soc., 1972,94, 3047. D. W. Goodman, M. J. S. Dewar, J. R. Schweiger, and A. H. Cowley, Chem. Phys. Letters, 1973, 21, 474. 'I3 R. S. Gay, B. Fontal, and T. G. Spiro, 1t:org. Chem., 1973, 12, 1881. '' J. D. Witt, L. A. Carreira, and J. R. Durig, J . ,4401. Structure, 1973, 18, 157. ' I G G . P. Gennaro and Y.-N. Tang, J . Inorg. Nuclear Chem., 1973, 35, 3087. 7 * W. S. Sheldrick, J.C.S. Dalton, 1973, 2301. 7 7 R. G. Cavell, J.C.S. Chem. Comm., 1974, 19. D. U. Robert, D. J. Costa, and J. G. Reiss, J.C.S. Chem. Comm., 1973, 745. ' I p J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1974, 15. M. A. Landau, A. S. Kabankin, and A. V. Fokin, Zhrtr. fir. Khim., 1973, 47, 2916. 81 H. Pobiner, Analyt. Chim. Acta, 1973, 67, 448.

'I1 'Ix

55

Halogenophosphinesand Related Compounds

phosphoranes ( 7 9 ,82 which appear to have axial trichloromethyl groups, and a study of N-alkylfluor~phosphoranes.~~ (C1,C),PCl,-, (75) n = 1 or 2

Preparation.-Lit tle significant preparative work has appeared this year. The preparation 49-51 of phosphoranes from halogenophoaphines and carbonyl compounds is discussed above, and the conversion49g51 of certain of these into phosphine oxides is discussed in Chapter 4. The perfluorophenylphosphorane (76) has been prepared.84 Dichlorotriethylphosphorane (77) is formed as a

F

F

Et,P

.t

2CuCI,

* Et,PCl,,CuCl (77)

(76)

copper complex as outlined, although it may exist as the isomeric phosphonium A re-investigation by e.s.r. of the product of y-irradiation of (78) suggestss6that the anion (79) is formed, and not the radical (80).87s88 PF,

(79)

f-

KPF,

+ PF4

(78)

(80)

Reactions.-This year’s literature reflects a welcome interest in attempts to understand the reactions of halogenophosphoranes with relatively simple organic molecules. Such a trend has produced unsuspected problems in mechanism for the organophosphorus chemist, and, fui thermore, yielded a number of synthetic reactions of potential use to organic chemists in general. The reaction of phosphorus pentachloride (81) with acetaldehyde under mild conditions is believed 89 to yield a 1 : 2 complex, which on treatment with 0 MeCHO + 2 x 1 ,

MeCHCIOkl,

%I,

II

C1,POCHClMe

E. S. Kozlov, S. N. Gaida-Maka, G. B. Soifer, Yu. N. Gachegov, and A. D. Gordeev, Zhur. obshchei Khim., 1913, 43, 156. M. Hausard, M. C. Labarre, and D. Voigt, J . Fluorirte Chem., 1973, 3, 375. G . G. Jakobson, G . G. Furun, and T. V. Terenmeva, Zhur. arg. Khim., 1973, 9, 1707. D. D. Axtell and J. T. Yoke, Znorg. Chem., 1973, 12, 1265. S. P. Mishra and M. C. R. Symons, J.C.S. Chem. Comm., 1974, 279. J. R. Morton, Canad. J. Phys., 1963, 41, 706. P. W. Atkins and M. C. R. Symons, J . Chem. SOC.,1964, 4363. V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 677.

56

Organophosphorus Chemistry 0

II

PhCCbMe -+ PhC(CI)=CH,

PhCMe

ms*PhC(Cl)=CHPC1,

0

II

PhC(Cl)=-CHFC1, (84 1

sulphur dioxide forms the phosphate derivative (82), albeit in poor yield. An examination of the complex reactions of methyl ketones with (81) has resulted in a rationalizationg0which appears to bear only slight resemblance to that suggested for acetaldehyde. For example, acetophenone with excess (8 1) gives predominantly the complex (83), which yields (84) in low yield. The problems of isolation of intermediates and products from these reactions appear to be substantial, and a better description of reaction pathways will depend upon fuller investigation of these problems. Ethyl acetate reacts with excess phosphorus pentachloride (81) to give 91 the acid chloride (85), after work-up with sulphur dioxide. When the molar proportion of ester is increasedyQ2 work-up yields (86), and its formation has 0

I1

MeCOEt

pas

MeCC1,OEt --+CH,=C(Cl)OEt

(87) 0

II

Cl,PCH=C(Cl)OEt

(86)

so, Cl,kH,CCl,OEt, PCI,

I iiR

i, XI,

ii,

so,

Cl,PCH,CCl + EtCl (85)

been rationalizedg2as shown. The intermediate vinyl ether (87) was not isolated, but its suggested reactions with (81) are analogous to several other addi-

#*

A. V. Fokin, A. F. Kolomiets, and V. S. Shchennikov, Zhur. obshchei Khim., 1973, 43, 801. V. M. Ismailov, V. V. Moskva, S. A. Novruzov, A. I. Razumov, Sh. T. Akhmedov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 212. V. M. Ismailov, T. V. Zykova, V. V. Moskva, S. A. NOV~LIZOV, A. I. Razumov, Sh. T. Akhmedov, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 1247.

Halogenophosphines and Related Compounds

57

tions of (81) to vinyl ethers 93 (seealso ref. 103). The acid chloride (86) has also been isolated 9 4 in similar fashion by another group, although the yield (5 %) is extremely low. On a more successful preparative note, a number of reactions of carboxylic acids or their derivatives with halogenophosphoranes appear to be of interest to synthetic chemists. For example, a simple reaction 96 between /I-keto-acids and (81) in benzene gives good yields of vinyl chlorides, such as (88), usually as

0

II

ArCCH,CO,H + PCl,

-+ ArC(Cl)=CHCO,H (88)

mixtures of geometric isomers. Related reactions of p-diketones O6 and simple ketones 9 7 have been described previously. Three papers have been devoted to a study of ester dealkylation by halogenophosphoranes to form alkyl halides. Thus alkyl salicylates (89) are

(89) converted Q8 in good yields (75-100 %) into alkyl chlorides by (81). A hightemperature reaction 9 9 of triphenylphosphine dibromide (90) with acyclic esters gives alkyl bromides. When (90) or (91) and esters or lactones are heated 0

1I R'COR2 + Ph,PBr,

0

II

lmoc, R'CBr + R2Br + Ph,P=O

(90)

Ph,PX,

+ PhCH=CHCO,Et

--+ PhCH=CHCOX,+

EtX

(90) X = Br (91) x = c1

in acetonitrile, carboxylic acid halides and alkyl halides are produced,loOas shown for ethyl cinnamate. These have been discussed in previous volumes - see J. A. Miller, in 'Organophosphorus Chemistry', ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1971, Vol. 2, p. 51; 1972, Vol. 3, p. 48. g 4 S. V. Fridland and Ya. A. Gorin, Zhur. obshchei Khim., 1973, 43, 946. M A.-H. Youssef and H. M. Abdel-Maksoud, J.C.S. Chem. Comm., 1974, 288. J. Carnduff, J. Larkin, J. A. Miller, D. C. Nonhebel, B. R. Stockdale, and H. C. S. Wood, J.C.S. Perkin I, 1972, 692. s 7 N. S. Isaacs and D. Kirkpatrick, J.C.S. Chem. Comm., 1972, 443. s* A. G. Pinkus and W. H. Lin, Synthesis, 1974, 279. A. G . Anderson and D. H. Kono, Tetrahedron Letters, 1973, 5121. l o oD. J. Burton and W. E. Koppes, J.C.S. Chem. Comm., 1973, 425.

Organophosphorus Chemistry

58

Other reactions of phosphorus pentachloride (81) with carboxylic acid derivatives include those with acrylonitrile (92),lo1as outlined, and with the lactone (93).loa 0

CH,=CHCN

+ PCl,

_.f

ii

ClCH,CCI,CC~N=PCl,

0

II

(92)

CICHzCC1,C(C1)~N-P(0)C1,

C~CH,CCl,C~-N

(93)

The reactions of phosphorus pentachloride (81) with olefins continue to be studied, notabIy by Russian groups. These reactions generally result in formation of a complex, the nature of which is not always clear, followed by decomposition of the complex either thermally or by the action of a chemical such as sulphur dioxide. For example, the vinyl ether (94) reacts lo3with (81) in 0

+ PCl,

ClCH=CClOMe

'*bjIcE:

(81)

(94)

It

=- Cl, PC(C1) =C (C1)O Me (95)

benzene to give the acid chloride (95) after work-up, and reactions of this type are believed to be involved in the later stages of the ester reactions 9 2 discussed above. A related study104has been directed towards an investigation of the role of phosphorus oxychloride in these reactions. Both isomeric allylic chlorides (96) and (97) yield lo6 the vinyl phosphonate

"'>i//

,

i. XI,

ii, so,

,f

(97)

(98) after treatment with phosphorus pentachloride (81), followed by the usual work-up procedures. Isoprene yields lo8the olefin (99) when treated with (81) if +

y:;

i,solvent ii,pin m, :

ClCH,CH=C(Me)CH,PCl, (99)

E. Fluck and F. Horn, Z . anorg. Chem., 1973, 398, 273. A. A. Avetisyan, A. N . Dzhanddzhadanyan, L. E. Astsatryan, and M. T. Dangyan, Khim. geterotsikl. Soedinenii, 1974, 310. * 0 3 V. M. Ismailov, V. V. Moskva, T. A. Babaeva, A. 1. Razumov, Sh. T. Akhmedov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 1011. l o * S. V. Fridland and Yu. K. Malkov, Zhiir. obshchei Khim., 1973, 43, 2169. l o 6 V. M. Ismailov, S. A. Novruzov, A. M. Krasilov, and Sh. T. Akhmedov, Zhur. obshchei Khim., 1973, 43, 1197. l O 6 V. V. Kormachev, A. V. Merkulov, and V. A. Kukhtin, Zhur. obshchei Khim., 1973,43, 21 57. lol

lo*

Halogenophosphines and Related Compounds

59

the resultant complex is quenched with white phosphorus in phosphorus trichloride. The reactions of (81) with olefins are often complicated by the presence of phosphorus trichloride, and a study107of this problem has been published. Further studies of 1,3-dioxolan ring-opening by phosphorus pentachloride (81) have appeared, and include a description10Bof new quenching conditions for the reaction of 2-methyl-l,3-dioxolan (100). With 2-methyl4chloromethyl1,3-dioxolan (101), the second stage of the reaction with (81) is slow, and the

I

(100) R = H (101) R = CH,C1

i, PCI, ii, so*

0

II

(CICH,),CHOCH=CHPCI, (103)

ether (102) may be isolated and then converted into the expected product (103). log Mechanistic evidence has been presented on the reactions of sily1:ethers with phenyltetrafluorophosphorane (104), and the scope of the reaction

-

RO

PhPF,

(104)

+ ROSiMe,

F

\!?---F Ph’

I

---+-

further exchanges

F

0

RF +--

II + I? k .t PhPF,

leading to alkyl fluorides discussed. The phosphoranes (55) have been found 5 5 to decompose as shown, and n.m.r. data on (55) published.55 Alcohols are known 111 to be converted into alkyl fluorides by reaction with either of the phosphoranes (105) or (lo@,and an investigation of the analogous V. V. Rybkina, V. G. Rozinov, and E. F. Grechkin, Zhur. obshchei Khim., 1973,43,62. S . V. Fridland, S. K. Chirkunova, and Yu. K. Malkov, Zhur. obshchei Khim., 1973,43, 279. l o o S. V. Fridland, S. K. Chirkunova, and T. V. Zykova, Zhur. obshchei Khim., 1973,43,51. 1 1 0 D. U. Robert, G. N. Flatau, A. Cambon, and J. G. Reiss, Tetrahedron, 1973,29, 1877. lo’

lo8

ll1

Y. Kobayashi, I. Kumadaki, S. Taguchi, and Y . Hanzawa, Chem. and Pharm. BUN. (Japan), 1972, 20, 1047.

Organophosphorus Chemistry

60 F

RO-PI

I3

--+

[ROPHF]+dHF

H ' I F

(55)

Ph"PF5-n

+ ROH

(104) n = 1 (105) n = 2

(106) n = 3

A

n = 2,3

olefin

*

RF

/

reaction of (104) has been presented.l12 It would appear that with (105) or (106) the alkyl fluoride is formed directly, but with (104), the authors present evidence that the alkyl fluoride is formed uia an olefin.l12When diols containing both a primary and a secondary alcohol group are treated with triphenylphosphinedibromide in DMF, the secondary hydroxyl is acylated, while the primary hydroxyl is halogenated, e.g. (107) to (108).'13

782

OCH=O I

bH (107)

F:

(108)

The products of the reactions of phosphorus pentachloride with the alcohols (109) are highly dependent upon the nature of R114 as outlined

pcI,

RCHOHCCI, (109)

EtCHClCCl, 18%

+ EtCCl=CCl, 13%

PhCHClCC1, 85%

R = CH,CH=CH,

ClCH,CH=CHCCl, 48%

(main products only). Cholesterol and i-cholesterol react with triphenylphosphine in carbon tetrachloride to give 116 mixture of 3-chlorides, dienes, and an unknown product retaining a phosphorus atom. The same reagent has been uSedlls in the Beckmann rearrangement, in 50-70% yield, of alkanone oximes (110) in THF. 11$

Y. Kobayashi, I. Kumadaki, A. Ohsawa, and M. Honda, Chem. and Pharm. Bull.

114

(Japan), 1973, 21, 867. R. K. Boeckman and B. Ganem, Tetrahedron Letters, 1974, 913. E. W. Reeve and T. F. Steckel, Canad. J . Chem., 1973,51,2017. R. Aneja, A. P. Davies, and J. A. Knaggs, Tetrahedron Letters, 1974, 67. R. M. Walters, N. Wakabayashi, and E. S. Fields, Org. Prep. Proc. Internat., 1974,6,53.

11'

61

Halogenophosphines and Related Compounds 0 Ph,Pin.

cct,

‘OH

I1

RCNHR

Triphenylphosphine in carbon tetrachloride, or the phosphorane (91), convert ll7, 118 ureas (111) into chloroformamidines(112), and the method can 0

II

Ph,P-CCl, oI Ph,PCZ +

R,NCNHAr (111)

R,NCCI=NAr (112)

(91)

be applied to products which are otherwise inaccessible. Phosphorus pentafluoride reacts ll0 with the condensation products of phenylglyoxd and amides. Phosphorus pentachloride has been treated120 with the silylamine derivatives (113) and (1 14) as shown. PF,

+ R,NSiMe, -+ R,NPF, + FSiMe, (113)

PF, + (Me3SiI2NR (114)

-

F3P-NR

I I

RN-PF,

The ammonolysis of bis(trifluoromethy1)trichlorophosphorane (115) has

been investigated.121Treatment of the phosphoranes (116) and (117) with trimethylsilane yields 122 derivatives of phosphorane (PH5). The reactions of F,CPF,

Me’SM

F3CPF, H,

phosphorus pentachloride or pentabromide with iodine r n o n ~ c h l o r i d eand ,~~~ of phosphorus pentafluoride with antimony p e n t a f l ~ o r i d e ,have ~ ~ ~ been described. R. Appel, K.-D. Ziehn, and K. Warning, Chem. Ber., 1973, 106, 2093. R. Appel, K. Warning, and K.-D. Ziehn, Chem. Ber., 1974, 107, 698. l l @ B. S . Drach, I. U. Dolgushina, and A. D. Sinitsa, Zhur. org. Khim., 1973, 9, 2368. l a 0 R. Schmutzler, J.C.S. Dalton, 1973, 2687. ln1 V. N. Prons, M. P. Grinblat, and A. L. Klebanski, Zhur. ubshchei Khim., 1973,43,692. l a * J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1973, 813. laa A.-R. Grimmer, Z . anorg. Chem., 1973,400, 105. la* G. S. H. Chen and J. Passmore, J.C.S. Chem. Cumm., 1973, 559. 11’

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

Phosphine oxides have fallen upon hard times, judging by the current literature, which this year has provided fewer publications on the subject than were reviewed in the first volume of this series! A timely reminder that the subject is nevertheless alive comes from the thorough reviews of phosphine oxidesY1 sulphides,2 selenides,2 and tellurides in the new edition of Kosolapoff’s compilation.s These chapters are likely to be of particular value to chemists requiring a quick guide to known structures and their preparation. 1 Preparation The synthesis of chiral phosphine oxides has stimulated effort in a number of laboratories in recent years. An elegant new approach to the problem involves the use of sugar-derived phosphorus heterocycles. These are 1,3,2-dioxaphosphorinan-Zones, such as (l), formed from glucosides and various phosphonic dihalides, such as (2). The preparation of chiral phosphine oxides Me 0 -0~ Me0

OMe

+

MeO

(2)

OMe

+ isomer at P Et.

.Me

(3 1 results from the separation and reaction of one isomer (at phosphorus) of (1) with two different Grignard reagents in succession, as outlined for ethylmethylpheny1phosphine oxide (3). H. R. Hays and D. J. Peterson, in ‘Organic Phosphorus Compounds’, ed. G. M. Kosolapoff a!d L. Maier, Wiley-Interscience, New York, 1973, Vol. 3, P. 341. L. Maier, in Organic Phosphorus Compounds’, ed. G. M. Kosolapoff and L. Maier, Wiley-Interscience, New York, 1973, Vol. 4, p. 1. ’ G. M. Kosolapoff, ‘Organophosphorus Compounds’, Wiley, New York, 1950. ‘ D. B. Cooper, T. D. Inch, and G. J. Lewis, J.C.S. Perkin I, 1974, 1043.

62

Phosphine Oxides, Sulphides, and Selenides

63

Another route to chiral phosphine oxides begins with tertiary phosphine sulphides, which, on treatment with acidic dimethyl sulphoxide, yield the correspondingphosphine oxides. When chiral phosphine sulphides (4) are used the products are oxides of inverted configuration.

Details6 have appeared of the preparation of phosphine oxides from phosphonic or phosphinic esters using hydride sources and alkyl halides.' The method is claimed to be convenient and give good yields, and is illustrated by the preparation of benzyldibutylphosphine oxide (5).

Syntheses in the phospholan series include the oxides (6),8 (7), and (8).g Of these, 1-methyl-3-phospholanone 1-oxide (6) has been studied in considerable detail.8 It is a keto-enol mixture, and the reactions outlined here reflect the reactivity of the hydrogens at C-2.8 The isomeric oxides (7) and (8) were prepared by photochemical methods. The A2-phospholen 1-oxide (8) undergoes an unusual photochemical reduction in alcoholic solution9 (see ref. 41).

0

It

TIo (CH,CH,CMe)2 O& 'Me

0

R. Luckenbach, Synthesis, 1973, 307. R. B. Wetzel and G. L. Kenyon, J. Org. Chem., 1974, 39, 1531. R. B. Wetzel and G. L. Kenyon, J. Amer. Chem. SOC.,1972,94, 1774. L. 33. Quin and R.C. Stocks, J. Org. Chern., 1974, 39, 686. H. Tomioka and Y . Izawa, Tetrahedron Letters, 1973, 5059.

Organophosphorus Chemistry

64

I

i,

B

U

~

H

5. -OH

+

eMe

OH ‘Ph

(8 1 (7) Diphenyltrifluoromethylphosphine oxide (9) and diphenyltrifluoroacetylphosphine oxide (10) have been reported lo to be produced by the pyrolysis of the tervalent ester (11). This observationcontrasts with the elusive behaviour of

(10) describedl1some time ago, and the isolation and fuller characterizationof the products from (11) are therefore eagerly awaited. The phosphine oxides (12) have been shown12 to be intermediates in the

R,PC1

+ PhCHO -+

0

II R,PCHPhCl

c1-

R

0

+ PhCHO

A

II

R,PCHPhOCHPhCl

formation of a-chloroalkylphosphine oxides (13) from phosphinous chlorides and benzaldehyde. The conversion of (12) into (13) appears to be a fragmentalo

l1

P. Sartori and R. Hochleitner, 2.anorg. Chem., 1974, 404, 164. E. Lindner, H.-D. Ebert, and P. Junkes, Chem. Ber., 1970, 103, 1364. N. J. De’Ath, J. A. Miller, and M. J. Nunn, Tetrahedron Letters, 1973, 5191.

Phosphine Oxides, Sulphides, and Selenides (PhCHCl),O

A

65

PhCHCI, + PhCHO

(14)

tion related to that previously observed13 for the ether (14), formed in the reaction of phosphorus trichloride with benzaldehyde. Similar results have been reported1* in the reaction of hexafluoroacetone with chlorodi-npropylphosphine (15), although the oxide (16) was found to be stable at

100 "C.In each of these systems, the oxides (12) and (16) are formed by reactions which resemble Arbusov-type dealkylations; the steps leading to (12) and (16) are discussed in Chapter 3. The preparation of a number of aminoalkylphosphineoxides from carbonyl compounds has been reported this year. For example, a Mannich-type reaction between the diamines (17), diphenylphosphine,and paraformaldehydeyields l5 Ph2PH + R2NCbCH2NHR + (CKO),,

_.t

P&PCH,NRCH,CH,NR,

(17)

Ph,

iL

H,NRCH,CH,NR,

(18)

the oxides (18), after an oxidation step. The oxides (18) are unusual in having three potential ligands. Related reactions with dialkylaminesl6or ureas lead to the oxides (19) and (20), respectively, which are of interest in the metal (rare earth) extraction and fire-retardant fields. 0

Ph,PCl + R2NH + CH20

II

Ph,PC&NR, (19)

J. A. Miller and M. J. Nunn, Tetrahedron Letters, 1972, 3953. V. N. Volkovitskii, I. L. Knunyants, and E. G. Bykhovskaya, Zhw. Vsesoyuz Khim. obshch. im. D. I. Mendeleeoa, 1973, 18, 112. l6 S. 0. Grim and L. J. Matienzo, Tetrahedron Letters, 1973, 2951. l o M. N. Rusina, Yu. M. Polikarpov, G. F. Yaroshenko, and L. M. Timakova, Zhur. obshchei Khim., 1973, 43, 238. l7 G. H . Birum, J . Org. Chem., 1974,39,209.

Organophosphorus Chemistry

66

0

R,POR' + PrCHO + (H,N),CO

H*,

0

II II R,PCHNHCNH, I Pr

(20)

Conjugate addition reactions to activated olefins have also been used to prepare phosphine oxides and sulphides. In general these reactions have been quite standard, as illustrated by the syntheses of the oxides (21),18(22),19and (23).lS

+ RCH=CHCO,H

Q

adduct

--+

Et I

/Et

0 i'CHRCH,CO,Me

S

S

II

II

Ph,PH + Me,PCH=CH,

base : Ph, PCH,CH,PMe,

0

II

Ph,PCH=CH,

$-

IZ- C,H,,NH,

ti

__f

Ph,PCH,CH,NHC,H,,

(23)

The synthesis of bisphosphine oxides, e.g. (24),20has attracted attention in this year's literature. 21 The object of much of this work is the application of 2os

Ph,kH,CH,OH

i, KOH ii, P a , iii, BqP(0)H*

+ lithium

0

0

II tl Yh,PCH,CH,PBu, (24)

bis-oxides to problems in complexation and extraction.22 A study of the formation of phosphine oxides by polyperoxide oxidation of phosphines in aqueous media has appeared.23

2 Reactions A detailed account 24 of the reduction of phosphine oxides by phenylsilane (25) has been published. This reagent is commercially available, gives 85-96 % V. K. Khairullin and R. Z. Aliev, Zhur. obshchei Khim., 1973, 43, 2165, R. B. King, J. C. Cloyd, and P. K. Hendrick, J. Amer. Chem. SOC.,1973, 95, 5083. J. Gloede, J. prakt. Chem., 1972, 314, 281. V. K. Khairullin, G. V. Dmitrieva, I. A. Aleksandrova, and M. A. Vasyanina, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 2744. K. B. Yatsimirskii, M. I. Kabachnik, Z . A. Sheka, T. Y. Medved, E. I. Sinyavskaya, N. P. Nesterova, and M. Konstantinovskay, Dokiady Akad. Nauk S.S.S.R.,1973,212, 428. H. D. Holtz, P. W. Solomon, and J. E. Mahan, J. Org. Chem., 1973, 38, 3175. K. L. Marsi, J. Org. Chem., 1974, 39, 265.

lB

ao p1

*a

ad

Phosphine Oxides, Sulphides, and Selenides -p\I T

........0

H...,....Si-Ph

H

67

7

,rn

I\

I I H

/Ph OSi-H

H ‘

H H

H-Si-Ph (25 1

yield of phosphine, and is extremely convenient to use compared with other silanes. However, perhaps even more significant, it also gives phosphines of 100% optical purity from chiral phosphine oxides. The same paper also contains a discussion of the mechanism of deoxygenation by phenylsilane, and the author’s conclusions are outlined here. Stereochemical aspects of the formation of phosphineirnines by reaction of p-tosyl isocyanate (26) with phosphine oxides have been The oxide

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

\(.

TsN=C=O = O)

I

+ TsN=C=S (50%) (5 0%)

(27a) gives the imine (28) with retention of configuration at phosphorus [shown by comparison with (28) made via tosyl azide], whereas chiral acyclic phosphine oxides give racemic i r n i n e ~This . ~ ~ difference has been ascribed 26 to the ease with which the initial 1 : 1 adduct (29) from the strained oxide (27a) 95

C . R. Hall and D. J. H. Smith, Tetrahedron Letters, 1974, 1693.

Orgmtophosphorus Chemistry

68

cyclizes. The sulphide (27b) is found to react with (26) as shown, and both this exchange and the results with acyclic oxides are rationalized26 in terms of intermediate 2 : 1 adducts. Epoxide deoxygenation by or via phosphine oxides or selenides continues to attract attention. Further study 26 of deoxygenation by triphenylphosphine selenide (30) 27 has implicated episelenide intermediates, and n.m.r., chemical,

and stereochemical evidence has been presented,26 although various episelenides have defied isolation. On a related theme, a new variant2* of the diphenylphosphide deoxygenation of epoxides is claimed to be experimentally more convenient than the previous method.2eThe new sequence is outlined here, and rests upon the easy formation, isolation, and thermal decomposition

T of the 8-hydroxyalkylphosphineoxides (31). As shown, the sequence may be used to invert olefin geometry. The addition of HX reagents to dialkyl(methylthioethyny1)phosphine oxide (32) under acidic or basic conditions results 30 in protonation of the triple bond on the carbon adjacent to phosphorus, It would appear 30 that the phosphoryl 0

(32)

'I IT

'8

' I 8o

\

Ha

li'

Me,PCH=C(Cl)SMe (34)

T. H. Chan and J. R. Finkenbine, Tetrahedron Letters, 1974, 2091. D. L. J. Clive and C. V. Denyer, J.C.S. Chem. Comm., 1973, 253. A. J. Bridges and G. H. Whitham, J.C.S. Chem. Comm., 1974, 142. E. Vedejs and P. L. Fuchs, J. Amer. Chem. Soc., 1973,95, 822. W. Hagens, H. J. T. Bos, and J. F. Ahrens, Rec. Trav. chim., 1973,92, 762.

Phosphine Oxides, Sulphides, and Selenides

69

group is the dominant factor controllingthese additions, as in the formation of the vinylphosphineoxides (33) and (34). Similar conjugate Grignard additions to the oxide (35) have been applied 31 to a neat synthesis of allenes in yields between 60 and 85%. After conjugate

0

II

Ph,PC=CR'

-t

R2MgX

i, Cur-ether U. PhCHO iii, H,O

(351

&

\

II ,CHPh

> Ph,PC 'CR1R2

0 PhCH=C=CR'R*

II

+ Ph,PONa

addition, the incipient carbanion is trapped by benzaldehyde and the resultant @-hydroxyphosphineoxides (36) treated with base to generate the allene. A more routine addition of malonate carbanions to the ethynylphosphineoxide (37) has been described.3a 0

0

I1

Ph,PC=CPh

+ CH,(CO,Et),

base

*

II

Ph,PCH=C(Ph)CH(CO,Et),

(3 7)

The phosphine oxides (38) and (39) rearrange33as shown. These reactions involve only phosphinyl migration, and this has been ascribed33to the 0

""x TsO

solvolysis

CD,

0

' y

PPh,

ACH,

CH,Br

M. B. Marszak, M. Simalty, and A. Seuleiman, Tetrahedron Letters, 1974, 1905. M. Dupre, Compt. rend., 1973, 277, C, 891. D. Howells and S. G. Warren, J.C.S. Perkin 11, 1973, 1472.

70

Organophosphorus Chemistry

unfavourability of alternativemethyl migration in each case. A further paper 3 4 in this series has been devoted to an examination of the problem of migratory aptitude and its assessment. The authors pinpoint succinctly the oversimplifications made in our current conception of migratory aptitude, and suggest that in carbonium rearrangements the dominant factor is the ability of the non-migrating group to support a positive charge. Generation and trapping of organophosphorus intermediates has been a favoured topic this year. For example, 2-phenylisophosphindole2-oxide (40)

1

McO,CCrCCO,Me

has been converted 36 into the corresponding phosphole (41), which undergoes ready Diels-Alder reactions as shown. The electron-deficient oxide (42) has previously36 been postulated as an intermediate in a-diazoalkylphosphine oxide photolysis, and (42) has now been trapped3' as a novel phosphinate (43) by reaction with benzaldehyde. Details have appeared of the trapping of

0

II

PhP=CPhR (42)

0 phcHo;

II

PhP-CPhR

I

I

O-CHPh (43)

s5

37

D. Howells and S. G . Warren, J.C.S. Perkin II, 1973, 1645. T. H. Chan and K. T. Nwe, Tetrahedron Letters, 1973, 4815. M.Regitz, A. Liedhegener, W. Anschutz, and H. Eckes, Chem. Ber., 1971, 104, 2177. M. Regitz, H. Scherer, W. Illger, and H. Eckes, Angew. Chem. Internat. Edn, 1973, 12, 1010.

M. Yoshifuji, S. Nakayama, R. Okazaki, and N . Inamoto, J.C.S. Perkin I , 1973, 2065.

71

Phosphine Oxides, Sulphides, and Selenicies 0

II

RPX,

0

a RP=O

EbS

*

II

RP(SEt),

(W Phccph

+

phosphinidene oxides (44)generated 3 y from phosphonyl dihalides. A further paper40 describes the reduction of one of these adducts. P h o t ~ l y s i sof~ ~ 3-alkyl-l-phenyl-A3-phospholen l-oxide (45) in alcoholic solution gives the esters (46) in good yield, apparently the result of photochemical generation of phenylphosphinidene oxide (cf. ref. 9).

(46)

(45)

3 Physicai and Structural Aspects Several attempts have been made to relate the basicity of phosphine oxides to spectroscopic parameters. For example, the lH n.m.r. shifts of phosphoryl compounds of general structure (47) have been used to measure the basicity of the P==Ogroup and its variation with the functions X and Y.42 0

Il/X MeP

‘ Y (47)

Protonation of phosphine oxides in aqueous sulphuric acid has been studied43by lH and 31P n.m.r., and the correlation of basicity with oxide structure used to set up a new HP-0 acidity function. Chemical studies on a related matter have revealed**the structure of the 1 : 1 adducts formed by a@ 40

41 4a

44

S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, J.C.S. Chem. Comm., 1971, 1186. S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, J.C.S. Perkin f, 1973, 2069. H. Tomioka, Y. Hirano, and Y. Izawa, Tetrahedron Letters, 1974, 1865. A. G. Cook and G. W. Mason, J . Inorg. Nuclear Chem., 1973, 35, 2090. N. K. Skvortsov, G. F. Tereshchenko, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim., 1973, 43, 981. H. Schmidbaur and K.-H. Riithlein, Chern. Ber., 1974, 107, 712.

Organophosphorus Chemistry

72 0

II

Me,P + RCO,H (48)

(49)

trimethylphosphine oxide (48) and acetic or formic acids. It is possible to distill and crystallize these adducts, for which structure (49) has been suggested. The phenolic ionization of phosphorus derivatives of general structure (50) 0

It

Me,PAr(OH) (50)

reveals 46 that all the phosphorus substituents are n-acceptors, as suggested by earlier work 47 in this area. Phosphine selenides (51) have been studied4*by 469

Se

II

GPR2

(51) R1 = R2 = Me R1 = R2 = Ph R1 = Me, R2 = Ph, OMe, or NMe, R' = Ph, R2 = OMeor NMe,

heteronuclear triple-resonance techniques. The 7Sen.m.r. shifts suggest that the P- Se bond has appreciable dipolar form. Ethynyldiphenylphosphine oxide (52) has 'J, 2J,and 3Jall positive.4Q

(52)

(53)

X-Ray data have been reported 6ov 61 for tetraphenylcyclotetraphosphine monosulphide (53), as have far4.r. spectra of triphenylphosphine oxide and E. N. Tsvetkov, M. M. Makhamatkhanov, D. I. Lobanov, and M. I. Kabachnik, Zhur. obshchei Khim.,1973, 43, 769. E. N. Tsvetkov, M. M. Makhamatkhanov, D. I. Lobanov, and M. I. Kabachnik, Zhur. obshchei Khim., 1970, 40, 2387. 4T E. N. Tsvetkov, D. I. Lobanov, M. M. Makhamatkhanov, and M. I. Kabachnik. Tetrahedron Letters, 1969, 5623. 48 W. McFarlane and D. S. Rycroft, J.C.S. Dalton, 1973, 2162. R.-M. Lequan, M.-J. Pouet, and M.-P. Simonnin, J.C.S. Chem. Comm., 1974, 475. I 0 H. P. Calhoun, M. R. LeGeyt, N. L. Paddock, and J. Trotter, J.C.S. Chem. Comm., 1973, 623. 61 H. P. Calhoun and J. Trotter, J.C.S. Dalton, 1974, 386. 'I

46

Phosphine Oxidks, &&hides,

and Selenides

73

1.r. and dipole measurements on the cyanomethyltriphenylarsine phosphine oxides (54) have been used53to determine their preferred conformation. Details of some of these papers appear in Chapter 12. 0

II

R,PCH,CN (54) R = Ph or Et

S . Milicev, Spectrochim. Acta, 1974,30A,255. 0. A. Raevskii, Y. A. Donskaya, V. G. Khalitov, and L. A. Antokhina, Izuesr. Akud. Nauk S.S.S. R., Ser. khim., 1973, 1339.

is 6s

5 Tervalent Phosphorus Acids BY B. J. WALKER

1 Introduction For the first time since the inception of this Report the total number of references appearing in this area has shown a significant decrease. Phosphinic acids and their derivatives have been reviewed. 2 Phosphorous Acid and its Derivatives Nucleophilic Reactions.-Attack on Saturated Carbon. The Arbusov reaction has been widely used in phosphonate synthesis.2This has been extended to the preparation of the unsymmetrical diphosphine ligand (2) through reaction of 0

(Pr’O),PPh

f

II Br(CH,),P(OPri),

0

1700c:

0

II II Ph(Pr’0) P(C€i2)2P(OPri)2

the bromophosphonate (1 ) with di-isopropyl phenylphosphonite, followed by hydride r e d ~ c t i o n ,and ~ to the synthesis of macrocyclic diphosphines from polymethylene dibromides. 2-Chlorometl~yloxazine(3) reacts with phosphines and phosphites to give Me

Me

I

I

P. C. Crofts, in ‘Organic Phosphorus Compounds’, ed. G. M. Kosolapoff and L. Maier, Wiley-Interscience, New York, 1973, 6, 1. E.g. A. I. Razumov, P. A. Gurevich, and S . Y u . Baigil’dina, Zhur. obshchei Khim., 1974, 44, 458 (Clzem. Abs., 1974, 80, 121 059); S. V. Kruglov, V. M. Ignat’ev, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khirn., 1973, 43, 1480 (Chem. Abs., 1974, 80, 15 021). R. B. King, J. C . Cloyd, jun., and P. N. Kapoor, J.C.S. Perkin I, 1973, 2226. T. H. Chan and B. S . Ong, J. Org. Chem., 1974, 39, 1748.

74

Terualent Phosphorus Acids

75

phosphonium salts and phosphonates (4), respectively, which through Wittigtype reactions provide routes to unsaturated aldehydes, ketones, and acids.s A new route to the relatively rare isophosphindole ring system (5) has been

(5)

reported through reaction of o-xylylene dibromide with triethyl phosphite. Phosphoryl sulphides (6),and hence the corresponding sulphoxides, have been prepared by a similar Arbusov reaction of a-chloro-sulphides. 0

ti

(R'O), PCH, SR2

A variety of Arbusov intermediates have been prepared from phosphites and alkyl halides and studied by n.m.r. spectroscopy.* In cases with simple alkyl substituents the intermediates (7) could not be detected; however, (8) +

(neo- C, H,, O),PR

X-

(8)

could be isolated and kept indefinitely in the absence of air and moisture. 31P n.m.r. spectroscopy showed the adducts to have phosphonium salt structures, and molecular weight, conductivity, and kinetic measurements all support ion-pairs rather than dissociated ions in chloroform. a-Ureidophosphonates (10) have been synthesized from ureas, aldehydes, and phosphite esters, and the proposed mechanism involves initial formation of the adduct (9), followed by attack of phosphite.

RCHO

" 1

(RO),PCHR* NH 2CQ

I)

rp"

+ H,NCONH, H*, RCHNHCONH, --+ 1

(RO&HRNHCONH,

0 RCHO- (RO),P

II

(RO),PCHRNH .CONH,

G. R. Malone and A. I. Meyers, J . Org. Chem., 1974, 39, 623. C. N. Robinson and R. C. Lewis, J. Heterocyclic Chem., 1973, 10, 395. M. Mikolajczyk and A. Zatorski, Synthesis, 1973, 669. H. R. Hudson, R. G. Rees, and J. E. Weekes, J.C.S. Perkin I, 1974, 982. G . H. Birum, J. Org. Chem., 1974, 39, 209.

76

Organophosphorus Chemistry

A new synthesisof @-unsaturated acids has been developed lothrough alkylation of dibenzyl phosphite anion followed by carboxylation to give the phosphonate (ll), which gives the olefin on reaction with aldehydes and two

(1 1)

moles of base. The reaction of diethyl phosphite with 1,3,5-tribenzylhexahydro-sum-triazine to give the aminophosphonate (12) has been used as the first step in a developing synthesis of 6H-~ephalosporins.~l 0

+ (EtO),PHo PhCH,N-NCH,

-+

PhCH,NHCH2P(OEtI2 II

Ph

H' (1 2) Attack on Unsaturated Carbon. Numerous reports of addition of tertiary phosphites,l2 secondary phosphites,13 and silyl phosphites l4 to activated olefins have appeared. The addition of secondary phosphites to acryloyl chloride in the presence of trhethylsilyl azide provides a route to 2-isocyanatoethylphosphonates(13).16 0

II

(RO),PCH, CH,NCO (13)

Cycloalkenyldiphosphonates (14) have been prepared from the corresponding dichloride by reaction with tertiary phosphites.ls A similar 0

(14)

reaction l7 with dimethyl a-bromovinylphosphonate gave the] trans-diphosG. A. Koppel and M. D. Kinnick, Tetrahedron Letters, 1974, 711. R. W. Ratcliffe and B. G. Christensen, Tetrahedron Letters, 1973, 4645. l a E.g. B. A. Arbuzov, T. D. Sorokina, A. V. Fuzhenkova, and V. S. Vinogradova, Zzuest Akad. Nauk S.S.S.R., Ser. khim., 1973, 2577 (Chem. Abs., 1974, 80, 60 003). I* E.g. M . M. Sjdky, F. M. Solirnan, and R. Shabana, Egypt. J . Chem., 1972,15,79 (Chem. Abs., 1973, 79, 92 327). l4 E.g. A. N. Pudovik, E. S. Batyeva, and G. U. Zamaletdinova, Zhur. obshchei Khim., 1973,43, 947 (Chem. Abs., 1973,79, 66 461). l' V. A. Shokol, V. F. Gamaleya, and L. I. Molyavko, Zhur. obshchei Khim., 1974,44,90 (Chem. Abs., 1974, 80,96 094). l a J. D. Park and 0. K. Furuta, Daehan Hwahak Hwoejee, 1973,17,67 (Chem. A h . , 1973,

lo 'l

79, 5418). l'

A. N. Pudovik and G. E. Yastrebova, Zhur. obshchei Khim., 1973,43,1647 (Chem. Abs., 1974, 80, 3585).

Tervalent Phosphorus Acids

77

phonate (15). The reaction of pentachloropyridine with trialkyl phosphites 0

0

0

I1 (MeO),PCBr=CH,

II It (MeO),P-CH=CH-P(OR),

+ (RO),P ---+

(15)

gives the expected Arbusov-type product (16) and 1,2,4,5-tetrachloropyridine, the latter presumably through attack on halogen.18

+ (RO),P --+

a

\

N

c1

ci

(16)

Paulisen has continued his investigation of the addition of secondary phospl~itesto unsaturated carbohydrates. The same mixture of a- and Bphosphonates is obtained from the reaction of either triacetate (17) or (18)

AcO (17)

CH,OAc I

\ H' '

/p/

AcO

yH,OAc

(RO)P4

BF,-E\O

1

2

I

OAc (18)

with dialkyl phosphites l9 and the results support a carbonium ion rearrangement mechanism. A similar, but base-catalysed, reaction of the p-glycoside (19) gave preferentially the phosphonate (20) ; however, an analogous reaction

J. Bratt and H. Suschitsky, J.C.S. Perkin I , 1973, 1689. H. Paulsen and J. Thiem, Chem. Ber., 1973, 106, 3850.

Organophosphorus Chemistry

78

02N

(22)

with the corresponding a-glycoside gave the phosphonates (21) and (22) in approximately equal amounts.2o Base-catalysed reaction of dialkyl phosphites with various carbonyl-containing carbohydrates [e.g. ( 2311 gave a-hydroxyphosphonates, generally stereoselectively.21

-&q *+l(q CH,-0

CH,-0

4 O

//P(OR), 0 The reaction of tervalent phosphorus amides containing a NH with activated olefins predictably gives phosphine imines, e.g. (24), through addition and

0

(23)

proton transfer.22 (E to), PN H Ph

+ CH,=CH C O * NHPh

__f

(Eto),PCH,CH,CONHPh

II

NPh (241

The phosphonate (25) has been obtained in moderate yield from the reaction 0

PhCH=CHNO,

(Meo)3p ButOH f

R.T.

II

(MeO),PCPhCH=NOH

I

OMe (25)

2u

H. Paulsen and W. Greve, Chem. Bcr., 1973, 106, 2114. H. Paulsen and W. Greve, Chem. Ber., 1973, 106, 2124. A. N. Pudovik, E. S. Batyeva, and N. V. Yastremskaya, Zhur. obshchei Khim., 1973,43, 437 (Chem. Abs., 1973,79, 5411); M. A. Pudovik, S. A. Terent’eva, and A. N. Pudovik, ibid., p. 2619 (Chem. Abs., 1974, 80, 83 139); A. N. Pudovik, E. S. Batyeva, and N. V. Yastremskaya, ibid., p. 2631 (Chem. Abs., 1974, 80, 83 134).

Tevvalent Phosphorus Acids

79

of B-nitrostyrene with trimethyl phosphite.23 No mechanism of formation is suggested, but, unlike aromatic nitro-compounds, nitro-alkenes are known to react in a very complex manner with tervalent phosphorus cornpo~mds.~* As with secondary p h o s p h i t e ~ ,tertiary ~~ phosphites add to ethyl thioacetylene to give the B-ethylthioalkenylphosphonate (26) rather than the a-analogue.26 (RO),P + E t S C E C H

ROH

0

II

(RO),PCH=CHSEt

(26)

The predictable reports of phosphite additions to Schiff bases have appeared.27Perhaps surprisingly, the imine (27) is sufficiently basic to form the salt (28) rather than the more usual addition product (29) on reaction with dialkyl

0

I1

(RO),PCHArNHMe (29)

phosphites.2 8 Optically active diethyl a-aminobenzylphosphonate has been prepared by reaction of the Schiff base (30) with diethyl phosphite and resolution of the resulting salt (31) as its diben~oyltartrate.~~ PhCH=N PhCH=N

0

\ CHPh + (EtO),P /P / \H

(30)

Et,N_ KO-

II

(EtO),PCHPh

I

+NH,

c1(31)

Interest in the addition of stcondary phosphites to aldehydes and ketones 43 24

as 26

P7 28

20

W. E. Krueger and J . R. Maloney, J. Org. Chem., 1973, 38, 4208. C. J. Devlin and B. J. Walker, J.C.S. Perkin I, 1973, 1428; C. J. Devlin and B. J. Walker, ibid., 1974, 453. B. J. Walker, in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1974, Vol. 5, p. 89. M. L. Petrov and A. A. Petrov, Zhur. obshchei Khim., 1973, 43, 691 (Chern. Abs., 1973, 79, 42 614). E.g. B. P. Lugovkin, Zhur. obshchei Khim., 1974,44, 106 (Chern. Abs., 1974, 80, 96 088). N. S. Kozlov, V. D. Pak, G. A. Gartman, and I. A. Balykova, Zhur. obshchei Khim., 1973, 43, 2360 (Chern. Abs., 1974, 80, 60 000). S. V. Rogozhin, V. A. Davankov, and Yu. P. Belov, Iruest. Aknd. Nauk S.S.S.R., Ser. khini., 1973, 955 (Chem. Abs., 1973, 79, 42 610).

Organophosphorus Chemistry

80

has decreased this year, although reports still appear.3o The reaction of aryl chloro-phosphites with cyclic ketones gives the corresponding cycloalkenylphosphonates (32).81 Chloral undergoes attack at the carbonyl group on

reaction with trimethylsilyl dialkyl phosphites 32 to give the phosphonate (33), which, on pyrolysis, forms the vinyl phosphate (34), possibly via the dipolar 0

0

(EtO),POSiMe,

+ C1,CCHO

II --+(EtO),PCHCCl,

140 "C

I

II

(EtO),POCH=CCI,

(34)

OSiMe, (33) OSiMe,

I

(EtO),!-CH--CCI3

I

0 (35)

form (35). A similar addition to the carbonyl group occurs33with biacetyl to give the phosphonate (36). 0

II

(EtO),POSiMe, + MeCOCOMe -+ (Eto), PCMe(0 SiMe,)CO Me' (36)

Several reports have appeared 36 of reactions of phosphites with acid chlorides to give acyl phosphonates (37), and in one case this reaction has been used 36 as a new route to a-amino-phosphonic acids through the oxime (38) and 349

E.g. R. S. Tewari and R. J. Shukla, Zhur. obshchei Khim., 1973, 43, 997 (Chem. Abs., 1973, 79, 66 476). I1 S. Kh. Nurtdinov, N. M. Ismagilova, V. S. Nazarov, T. V. Zykova, R. A. Salakhutdinov, R. B. Sultanova, and V. S. Tsivunin, Zhur. obshchei Khim., 1973,43, 1251 (Chem. Abs., 1973, 79, 66 478). aa A. N. Pudovik, T. Kh. Gazizov, and Yu. I. Sudarev, Zhur. obshchei Khim., 1973, 43, 2086 (Chem. Abs., 1974, 80, 3581). aa A. N. Pudovik, A. M. Kubardin, A. P. Pashinkin, Yu. I. Sudarev, and T. Kh. Gazizov, Zhur. obshchei Khim., 1974,44, 522 (Chem. Abs., 1974, 80, 133 552). E.g. V. M. D'yakov and M. G. Voronkov, Zzvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 399 (Chem. A h . , 1973, 79, 5402). a b S. Asano, T. Kitahara, T. Ogawa, and M. Matsui, Agric. and B i d . Chem. (Japan), 1973, 37, 1193 (Chem. Abs., 1973, 79, 66468). *O

81

Tervalent Phosphorus Acids 0 (R'O),P + RzCOCl --+

It

(R'O),PCOR* (3 7)

reduction. Pyrophosphites 36 react differently with acyl chlorides to give a mixture of acyl phosphite and halogenophosphite (39).

+

A number of examples of the cycloaddition of phosphites to ap-unsaturated ketones to give the expected adducts (40) have been de~cribed.~'However,

reactions of tervalent phosphorus compounds with hexafluoroacetone azine give therearranged product (42);58 two possible mechanisms are discussed for the formation of (42), each involving the dipolar intermediate (41). E. E. Nifant'ev, I. V. Konlev, I. P. Konyaeva, A. 1. Zavalishina, and V. M. Tul'chinskii, Zhur. obshchei Khim., 1973,43, 2368 (Chem. Abs., 1974,80, 59 998). B. A. Arbuzov, V. M. Zoroastrova, G. A. Tudrii, and A. V. Fuzhenkova, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 2581 (Chem. Abs., 1974, 80, 48 100); B. A. Arbuzov, Yu. V. Belkin, and N. A. Polezhaeva,'ibid., p. 1107 (Chem. Abs., 1973, 79, 66 472); M. P. Gruk, N. A. Razumova, and A. A. Petrov, Zhur. obshchei Khim., 1973, 43, 945 (Chem. Abs., 1973,79, 66 466). K. Burger, W. Them, and J. Fehn, Chem. Ber., 1974,107, 1526.

82

Organophosphorus Chemistry

"YF3 N

"

f

R,P

ACF3

CF,

Borowitz and his co-workers have carried out a detailed comparative study of the reactions of phosphinites, phosphonites, and phosphites with ahalogenoketones.39 The balance between keto-phosphorylation and enolphosphorylation favours the former with increasing oxygen content of the phosphorus compound, higher temperature, more polar solvents, and bromorather than chloro-ketones. ma'-Dibromobiacetyl reacts with two moles of phosphite to give the double Perkow product (43)and no trace of the alternative Arbusov product or of the phosphorane (45). The rate of the first Perkow BrCH,CO*COCH,Br

+ 2(RO),P

k , P

-

\c-cGH2

CH, (RO),PO

CH,= C-

I

II 0

COCH,Br

'

'OP(OR1,

It

0

(po)3p
reaction must be much greater than that of the second since a high yield of the mono product (44)is obtained with one mole of phosphite. Attack on Nitrogen. The kinetics of the reaction of diazonium salts with dimethyl phosphonate have been studied.*lThe almost third-order behaviour supports the mechanism shown, involving a phosphonate anion rather than a as 40 41

I. J. Borowitz and R. K. Crouch, Phosphorus, 1973, 2, 209. M. L. Honig and M. L. Sheer, J. Org. Chem., 1973, 38, 3434. E. S. Lewis and E. C. Nieh, J . Org. Chenr., 1973, 38, 4402.

83

Terualent Phosphorus Acids

phosphite intermediate. From U.V. spectra the aryl azophosphonate (46) appears to be formed with syn stereochemistry. 0

II

+ Base

(MeO),P-H

+ HBase

(MeO)2P-6

0

+ ArN;

(MeO),P-O-

I1

--+ArN=N-P(OMe),

(46)

The betaine (47),derived from the reaction of tris(dimethy1amino)phosphine and dialkyl azodicarboxylate, has been used 4 2 to prepare monosaccharide

+ (Me,N),P

R'O,CN=NCO,R1

--+

R'O,CN-NCO,R'

I

(Me,N),P + (47) HO./

OR'

n'

R'O~CN-NHC-OR'

J [R'O,CN=NH]

+ (Me,N),P + R'OCOR2

II

8 (4 8)

carbonates (48) from the corresponding alcohols. In N-aryl-N'aryoldi-imides (49) react readily with tervalent phosphorus esters to give cyclic Ph Ph

\/

\

0

I N

/c=Y

+

++N

I

Ph

43

G. Grynkiewicz, J. Turczak, and A. Zamojski, J.C.S. Chem. Comm., 1974, 413. W. C. Hamilton, J. C. Ricci, jun., F. Ramirez, L. Kramer, and P. Stern, J. Amer. Chem. Sor., 19'13, 95, 6335. 4

84

Organophosphorus Chemistry

tetraoxyazaphosphoranes, e.g. (50). In the case of (50), X-ray crystallography shows the structure to be largely trigonal bipyramidal, with some modification to accommodate the constraint imposed by the adamantanoid ring system. Attack on Oxygen. The stoicheiometry and rate constants of the reactions of

0

It O-P(OR),

q, \ /

8 i OH

I

0-P(OR),

I

\

OH

J

\OH

OH

Terualent Phosphorus Acids

85

triphenylphosphineand triphenyl phosphite with ozone have been The rate was first-order in each reagent and ca. 10 times faster with the phosphine than with the phosphite. Trialkyl phosphitesreact with diphenoquinoneto give a variety of all thought to be formed by initial attack of phosphorus at oxygen to give (51). A similar reaction with diphenoquinonedibenzenesulphonimide gives the phosphoramidate (52) as the only product. 0

II

R~SO,NP(OR~), I

NS0,R’

In the reaction of isocyanato-phosphites46 with hexafluoroacetone, attack on oxygen gives the intermediate (53), which on cyclization and further

(RO),PNCX + (CF3)2C0 X = SorO

_.+.

reaction with ketone gives the isolable bicyclic phosphorane (54).A similar reaction with diphenylvinylphosphinegives the analogous product ( 5 3 , which undergoes a Wittig elimination on pyrolysis to give the unsaturated phosphinate (56). The amino-phosphite(57) reacts with hexafluoroacetone via the ** S . D. Razumovskii and G. D. Mendenhall, Canad. J. Chem., 1973,51, 1257. u

M. M. Sidky, M. R. Mahran, and Y. 0. El-Khoshnieh, Tetrahedron, 1974,30, 47. E. Duff,S. Trippett, and P. J. Whittle, J.C.S. Perkin I, 1973, 972.

Organophosphorus Chemistry

86

imine (58) to give the phosphordne (59), which also undergoes a Wittig-type elimination on pyrolysis.

Tris(dimethy1amino)phosphine desulphurizes @-keto-sulphides(60) to give ketones and enol ethers as major products;47a mechanism involving initial 0

0

It

II

Ph

(Me,N),P+

Ph

ph/c\/ph

(Me,N),kEt

(Me,N),P=S

displacement at sulphur is suggested. A similar reaction with benzyl thiocyanate gave a variety of products, including benzyl cyanide and dibenzyl sulphide. Desulphurization with trialkyl phosphites has been used 4 8 to convert p-lactam disulphides (61), formed from trapping sulphenic acids with thiols, into the corresponding sulphide (62), although some ring-opened product (63) was also formed. 47

D. N. Harpp and S. M. Vines, J. Org. Chem., 1974, 39, 647. R. D. Allan, D. H. R. Barton, M. Girijavallabhan, P. G. Sammes, and M. V. Taylor, J.C.S. Perkin I, 1973, 1182.

Tervalent Phosphorus Acids

87

+ (RzO),P

(61)

PhCH,CONH NH

C02CH,CCI,

(62)

SEt

(63)

Attack on Hcrlogeiz. The expected ethynylphosphonates, e.g. (64),are the products of the reaction of bromoacetylenes with dialkyl phosphite anions.49

1,2-Dihalogenoethyl cyanides undergo dehalogenation to acrylonitrile on reaction with either secondary or tertiary phosphites,60presumably through initial attack of phosphorus on halogen. Surprisingly,bis(diphenylphosphiny1)amine (65) is the product of the reaction of sodium diphenylphosphide and

BrxxBr + 4Ph2PNa

Br

Br

Ph,P),NH (65 1

1,2,4,5-tetrabromobenzenein liquid ammonia.61 o-Dihalogenobenzenes are known to undergo dehalogenation with metal phosphides, 5 2 and in this case initial attack of phosphorus on bromine followed by reaction with ammonia seems a likely mechanism. 49

51

62

I. N. Azerbaev, T. A. Yagudeev, Zh. K. Konysbaev, and T. G. Sarbaev, Doklady Vses. Konf. Khirn. Atsetilena, 4th, 1972, 2, 3 (Chem. Abs., 1973,79, 92 337). B. A. Arbuzov, A. D. Novosel'skaya, and V. S. Vinogradova, Zhur. obshchei Khim., 1973, 43, 2604 (Chem. Abs., 1974, 80, 70 892). J. Ellermann and W. H. Gruber, Z . Naturforsch, 1973, 28b, 310 (Chem. Abs., 1974, 80, 96 108). R. L. Stevens and B. J. Walker, unpublished results.

88

Organophosphorus Chemistry

The factors controlling the site of attack of halogenophosphonium cations

on ambident anions have been i n ~ e s t i g a t e dfor ~ ~(66) and shown to be quite

different for phosphines as compared with tervalent phosphorus compounds containing oxygen or nitrogen. The reactions of N-chloroguanidine6 4 and trichloromethyl isocyanate65 with tertiary phosphites give the salt (67) and the phosphonate (69) respectively. RNHC-NCl

I

+

(PhO),P

C13CNC0

-

+

(PhO),P-N=C-NHR

I

C1'

R

In the latter case the isocyanate exists largely as its tautomer (68) and the extent of phosphorw substitution depends on the ratio of the original reactants. Predictably, aminophosphonium salts are the products of the reaction of aminophosphines with chloramines.66 Several reports dealing with the use of halogenophosphonium salts in synthesis have appeared. Castro's group has extensively investigated the reaction of tris(dimethy1amino)phosphine with carbon tetrachloride in the presence of various hydroxyl-containing compounds. lY3-Diols give the alkoxyphosphonium salt (70), which can give the oxetan (71)67or provide a route to a variety of 3-substituted alcohols (72),68depending on the conditions used. One advantage of this system is that rearrangement of the neopentyl 6a

64 L6

6e

67

M. F. Pommerat-Chable, F. Tonnard, M. Hassairi, and A. Foucaud, Tetrahedron, 1973, 29, 4219. A. Heesing and G . Imsieke, Chem. Ber., 1974, 107, 1536. V. A. Shokol, B. N. Kozhushko, and A. V. Kirsanov, Zhur. obshchei Khim., 1973,43, 544 (Chem. Abs., 1973,79, 42 617). K. Issleib and M. Lischewski, Synth. Inorg. Metal-org. Chem., 1973,3,255 (Chem. Abs., 1973, 79, 92 331). B. Castro and C. Selve, Tetrahedron Letters, 1973, 4459. B. Castro, M. Ly, and C. Selve, Tetrahedron Letters, 1973, 4455.

89

Tervalernt Phosphorus Acids

/

RzOH/R20Na

CH

/ R2c\

T*

/ CH2

F-

= pF')

(71)

'CH,OH (72) Y = Br,i,N,,orPhS

group does not occur. The use of N-chlorodi-isopropylamine has many advantages over carbon tetrachloride in all of these reaction^.^^ The biomophosphonium salt (73), derived from tris(dimethy1amino)phosphine and bromine, reacts rapidly with carboxylic acids to give the corresponding anhydrides and hexamethylphosphorictriamide.60

km*H Me,N),PO + RCO,COR

The reaction of tervalent phosphorus compounds with N-bromosuccinimide in the presence of alcohols provides an alternative route to the alkoxyphosphonium salt (74)and hence to alkyl halides.61In the absence of alcohols,

JPOH (PhO),P=O

+ RBr

quite different reactions take place depending on the alkyl phosphite used.62 In all cases initial attack appears to be at phosphorus to give (73, which can 6s 6o 61

B. Castro, Y . Chapleur, and B. Gross, Tetrahedron Letters, 1974, 2313. B. Castro and J. R. Dormoy, Tetrahedron Letters, 1973, 3243. A. K. Bose and B. Lal, Tetrahedron Letters, 1973, 3937. D. J. Scharf, J. Org. Chem., 1974, 39, 922.

Organophosphorus Chemistry

90

react in three ways. If the phosphite alkyl group has no a-branching, attack of nitrogen on phosphorus takes place followed by an Arbusov reaction to give N-(dia1kylphosphonyl)succinimide (76). In the case of trimethyl phosphite or

+6 + (RO),P

0

-

/ 31

n&yl

Xi(OR),

c + i 6 0 (75)

\R

= Me

\

X

I

N-TM&(OMe),

0

But, rtc.

0

0

II

NMe + (MeO),PX

0

1 0

It

0

alkyl phosphites with a-branching, only a low yield of the Arbusov product (76) is formed; the main pathways involve, in the former case, attack on methyl to give N-methylsuccinimide and, in the latter case, elimination to give succinimide and olefin. Electrophilic Reactions.-Various substituted diarylphosphine oxides have been prepared by the reaction of dibutyl phosphite with the corresponding aryl Grignard reagent. as

M. I. Shandruk, N. I. Yanchuk, and A. P. Grekov, Zhrtr. obshchei Khim., 1973,43,2194 (Chem. Abs., 1974, 80, 37 222).

91

Tervalent Phosphorus Acids

Various studies of transesterification of phosphorous esters have been reported.64The hexaco-ordinate phosphorus anion (78) has been prepared 66

(77)

Et&H

(78)

by the base-catalysed reaction of 2-alkyl-l,3,2-benzodioxaphosphole(77) with pyrocatechol. Ph Ph

2-Oxo-3-phenyl-l,3,2-oxazaphospholan (79) has been prepared by mild hydrolysis of the corresponding 2-chloro-compound.

Dialkyl chlorophosphites react with silylamines (80) and (82) to give the aminophosphites (81) and (83), re~pectively.~~ It is also possible to prepare (84) through a similar route by removing two silyl groups. Japanese workers have developed68a new synthesis of ureas and thioureas through the reaction of carbon dioxide or carbon disulphide with diphenyl phosphite and primary amines. The reaction is thought to take place via an intermediate (85), followed by elimination to give isocyanate or direct displacement by amine. The principles of this new synthesis have also been applied 6 9 to the preparation of peptides and amino-acid esters. O4

as

E.g. P. N. Zavlin, D. N. D’yakonov, V. M. Al’bitskaya, and E. I. Babbina, Zhur. obshchei khim., 1973,43, 1651 (Chem. Abs., 1974, 80, 15 018). M. Wieber and K. Foroughi, Angew. Chem., 1973, 85, 444; M. Wieber, K. Foroughi, and H. Klingl, Chem. Ber., 1974,107, 639. M. A. Pudovik and A. N. Pudovik, Zhur. obshchei Khim., 1973, 43, 2144 (Chem. Abs., 1974, 80, 48 109). H. Binder and R. Fischer, Chem. Ber., 1974, 107, 205. N. Yamazaki, F. Higashi, and I. Iguchi, Tetrahedron Letters, 1974, 1191. N. Yarnazaki and F. Higashi, Tetrahedron, 1974, 30, 1323.

Organophosphorus Chemistry

92

R:

N+ (PhO),PHo

+ R'NH, + CX, -%

I

R'NHCX*X-P-OPh

H '

H/ H O '

RIN=C=O

R'NHCONHR'

+

PhOH

Attempts to brominate the acetylenic alcohol (86) with phosphorus tribromide give low yields of either 2-bromo-3,5-di-t-butyl-l,2-oxa-A3-phospholen2-oxide (87) or the allene (88), depending on the availability of protons PBr, + +C-C-CH+

I

CHCl,

Br

OH

I

(86)

+

+CH=C=C

+

% 'Br

from the The intermediacy of the cyclic salt (89) in the formation of (87) was established by low-temperature n.m.r. Rearrangements.-Both propargyl alcohol and propargyl mercaptan give the corresponding allenylphosphonates (90) and (91) on reaction with tervalent phosphorus acid ~ h l o r i d e sIn .~~ the case of a similar reaction with the acetylenic diol(92) a double rearrangement occurs 72 to give the diphosphonate (93), 'O

R. C.Elder, L. R. Florian, E. R. Kennedy, and R. S. Macomber, J. Org. Chem., 1973, 38, 4177.

71

R. M. Eliseenkova, N. I. Rizpolozhenskii, and V. D. Akamsin, liuest. Akad. Nuuk S.S.S.R., Ser. khim., 1973, 2755 (Chem. Abs., 1974, 80, 83 143). M. Huche and D. Cresson, Tetrahedron Letters, 1973, 4291.

Tervalent Phosphorus Acids

93 0 HC=CC&OH

R1PClSR2 -

I

*

HCECCKSH

II

R1(R2S)PCH=C=CH, (90)

S

II

R1(R2S)PCH=C=CH2 (91)

2(RO),PCl + HOCH,C=CCH,OH

while the enyne system (94) undergoes a very slow conjugated rearrangement to the allene (95).

Cyclic Esters of Phosphorous Acid.-Two groups 73* '* have investigated the conformational preference of amino-substituents on phosphorus in 1,3,2dioxaphosphorinans. Dipole moment and n.m.r. measurements show 73 that

'' J. A. Mosbo and J.

G. Verkade, J. Amer. Chem. SOL, 1973,95, 4659. W. G. Bentrude and H.-W. Tan, J. Amer. Chem. SOC.,1973,95,4666.

94

Organophosphorus Chemistry

dinitrogen tetroxide oxidation of the cyclic phosphites (96) and (97) occurs with retention of configuration at phosphorus. This information is used to

OM0 (96)

(9 7)

determine the configuration at phosphorus of 2-oxo-2-dimethylamino-l,3,2dioxaphosphotinans (98) and (99), formed by oxidation of the parent phosphoramidites (100) and (101). The results indicate that, in contrast to most other substituted dioxaphosphorinans, an equatorial dimethylamino-group is the more stable conformation. An explanation based on steric effects through vicinal interactions along the P-N bond is offered. Results obtained 7 4 from n.m.r. studies of 5-t-butyI-2-dimethylamino-l,3,2-dioxaphosphorinans (102)

and their derivatives support the preferred equatorial orientation of the dimethylamino-group in (102), and a similar explanation is put forward. Miscellaneous Reactions.-Mixed alkylalkoxydiphosphines (103) have been prepared 76 from secondary phosphites and chlorophosphines under basic conditions; the alternative reaction between secondary phosphine and chlorophosphite gave much lower yields. Surprisingly, oxidation of (103) with rS

V. L. Foss, Yu. A. Veits, V. V. Kudinova, A. A. Borisenko, and I. F. Lutsenko, Zhur. obshchei Khim., 1973,43, 1000 (Chem. Abs., 1973,79, 53 471).

Terualent Phosphorus Acids

95 0

(R'O),PH + RiPCl

Et,NL

I

(R'O),P--PR:

(R'O),P-PR:

mercuric oxide gave (104); the preferential oxidation at the phosphite centre is thought 7 6 to involve rearrangement of the intermediate (105) as shown. Phosphites have been used to cyclize peptides, e.g. in the synthesis of valinomycin. The reaction of chlorophosphites78 with the phosphinate (106) gave dialkyl 0

(R'O),PCl

II + R'(EtO)PCH,CH(OEt),

0 --+

11

(R'O),POEt + R'(EtO)PCH,CHClOEt

(106)

J 0

I1 (R'O),PH + EtCl

(107) 0

II

+ R'(EtO)PCH=CHOEt (108)

phosphite, alkyl chloride, and the vinylphosphinate (108). The initial reaction is thought to be formation of trialkyl phosphite and chloro-ether (107).

The cyclic phosphinates (110) are the products of the cycloaddition of nitrilimines to acetylenylphosphonites (109) regardless of the substituents.79 76

77 78

79

Yu. A. Veits, A. A. Borisenko, V. L. Foss, and 1. F. Lutsenko, Zhur. obshchei Khim., 1973, 43, 440 (Chem. Abs., 1973,79, 5416). M. Rothe and W. Kreiss, Angew. Chem. Internat. Edn., 1973, 12, 1012. M. B. Gazizov, A. I. Rammov, L. P. Syrneva, and L. G. Rudakova, Zhur. obshchej Khim., 1973,43, 2787 (Chem. Abs., 1974, 80, 70 896). L. A. Tamm, V. N. Chistokletov, and A. A. Petrov, Zhur. obshchei Khim., 1973,43,2178 (Chem. A h . , 1974, 80, 48 108).

96

Organophosphorus Chemistry

3 Phosphonous and Phosphinous Acids and their Derivatives The selenide (111) has been prepared from t-butylphenylphosphineoxide and resolved via its salt with (+ )-l-aminoethylbenzene.so Ph B ~ ~ P+ HSe

II

0

EtaN

*

Ph B ~ P - OH

II

B. Krawiecka, Z. Skzypczynski, and J. Michalski, Phosphorus, 1973, 3, 177.

6 Quinquevalent Phosphorus Acids BY

N. K. HAMER

1 Phosphoric Acid and its Derivatives Synthetic Methods.-No substantially new developments have appeared in this field during the past year. Among active esters investigated as practical phosphorylating agents is tris-(8-hydroxyquinolyl)phosphate,1v which, in pyridine solution, reacts with unpi otected nucleosides to give, after hydrolysis with aqueous cupric ion, good yields of the 5’-phosphates (Scheme 1).

I

OH ‘ O w a s e

OH

OH Scheme 1

Another, and seemingly very powerful, reagent is the cyclic mixed anhydride (la), which is very readily opened by attack at phosphorus by alcohols or The anion (lb), from dealkylation of (la) phenols even in the absence of with a tertiary amine, is also an active phosphorylating agent for alcohols. Since the residual ketol group is easily removed, these compounds may prove to be useful additions to existing reagents. NN’-Diphenylphosphorodiamidicchloride has been recommended as a convenient phosphorylating reagent for the preparation of nucleoside 3’phosphates since it is stable, it gives very high yields, and the resulting esters l

H. Takaku, Y . Shimada, and K. Arai, Bull. Chem. SOC.Japan, 1974,47, 779.

* H. Takaku and Y. Shimada, Tetrahedron Letters, 1974, 1279.

* F. Ramirez, S. L. Glaser, P. Stern, I. Ugi, and P. Lemmen, Tetrahedron, 1973,29, 3741.

97

Organophosphorus Chemistry

98

w 0

O\

/o

P

+

R’oH

ON ‘RI

+O-LoR2

0

(1)a; R’ = Me0 b; R’ = 0-

+ co,

I R’

are converted into phosphate monoesters by nitrosation.* Of less practical use owing to indifferent yields is the cyclic phosphorodiamidate ester (2), which reacts with simple alcohols to give products of both exocyclic and endocyclic

\

I

1

0

II

NH-P-OR NH2

(3 1 0

II aNH-I;OPh NH2

0

It 1 OH

RO-P-OPh

(51

cleavage (3) and (4), the latter being converted in part into the former by prolonged reaction. The related ester (5) in its free acid (or zwitterion) form gives phosphate diesters with alcohols.6 Full details of the synthesis of unsymmetrical diesters of pyrophosphoric acid by the reaction of the disilver salt of a monoester of phosphorothioic acid and a phosphate monoester have been published.’ In view of the good yields, the mild conditions, and the absence of synimetrical pyrophosphate byproducts it appears to be superior to previous routes to the nucleotide pyrophosphate coenzymes. Further, the findings that the procedure is insensitive to

a

J. Smrt, Tetrahedron Letters, 1973, 4727. T. Koizumi, Y.Arai, and E. Yoshii, Tetrahedron Letters, 1973,4763. T. Koizumi, Y.Arai, and E. Yoshii, Chem. and Pharm. Bull. (Japan), 1972, 22,468. I. Nakagawa and T. Hata, Bull. Chem. Soc. Japan, 1973,46,3275.

Quinquevalent Phosphorus Acids

99

small amounts of water and does not need to be carried out in homogenous solution represent additional advantages in nucleotide work. The 9-fluorenylmethyl group (6) has been suggested as a useful addition to 0

(61

the phosphate-protecting groups for the synthesis of deoxyribonucleotides. It is easily introduced, removed by mild base (aqueous ammonia), and increases the solubility in organic solvents. Another protecting group which is claimed to be much preferable to others in the synthesis of chains of more than six nucleotides via the triester method is the 4-methylthiophenyl ester (7), which, R20

M ~ (-)S-o[o;,

NaOl-Base

-

~

I

0R' (7 )

like several protecting groups containing a thioether link, is removed by oxidation (hypoiodite or N-chlorosuccinimide)followed by base. The related phenolic ester group (8), also removed by oxidation, has been used successfully for protecting phosphate mon~esters.~ 0

ROPO,H, + Ph,C++ 0

Ph,CNI-! 0(8)

1,4-Dibromobutane-2,3-dione reacts with triethyl pliosphite in a double Perkow reaction, giving the novel ester (9) lo while reaction of butane-2,3-dione

BrCH,*COCOCH,Br + (EtO),P

_.f

+fOP(OE II

t)*

* K. Itakura, C. P. Bahl, N. Katagiri, J. J. Michniewicz, R. H. Wightman, and S. A. Narang, Canad. J. Chem., 1973,51, 3649. E. Ohtsuka, S. Morioka, and M. Ikehara, J . Amer. Chem. SOC.,1973, 95, 8437. l o M. L. Honig and M. L. Sheer, J . Org. Chem., 1973, 38, 3434.

100

Organophosphorus Chemistry

itself with dimethyl phosphorochloridite gives directly the cyclic phosphate (l0).l1 Phosphorus pentachloride with methyl vinyl ketone gives, after treat-

(1 1)

ment with sulphur dioxide, the enol phosphate (11).12 In a similar reaction with acetaldehyde, phosphorus pentachloride gives 1-chloroethyl phosphorodichloridate (12). MeCHO

+;:,:

,OPOCL, MeCH ‘Cl (1 2)

//”

R’CN + (R20),P \SH (1 3)

(RzO),P\Ns + R’CSNH, OH

The readily available 00-dialkyl phosphorodithioicacids (13) are converted into the corresponding phosphorothioic acids by reaction with nitriles in the presence of limited amounts of water.14 In view of the initial difficulty encountered in preparing the sulphur analogue, the simple synthesis of the selenopyrophosphate ester (14) from seleniousacid and the cyclic phosphonate (15 ) is remarkable. l5

E. M. Gaydou, R. Freze, and G. Buono, Bull. SOC.chim. France, 1973, 2279. V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1974, 44, 707. V. V. Moskva, L. A. Bashirova, A. I. Razumov, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1973, 43, 677. l4 A. Nakanishi and S . Oae, Chem. and Ind., 1973, 274. l 6 D. S . Rycroft and R. F. M. White, J.C.S. Chem. Comm., 1974, 444. l1 I*

101

Quinquevalent Phosphorus Acids

o-Iodosophenyl phosphate has been prepared by peracid oxidation of the corresponding iodo-compound and shown to exist in the cyclic form (16).18 .O

(1 7)

(16)

Another unusual phosphate ester reported is that of the en01 from:malonic ester (17), formed by reaction of sodio diethyl malonate with diethyl phosphorochloridate.l7 The preparation and configurational assignments of a series of cyclic 4,6phosphate esters of 1,2,3-trimethylglucopyraoside(18a) and the corresponding esters of 1,2,3-trimethylgalactopyranoside(18b) have been described.l* In x(0)P:

0 ‘

OMe (18a)

* both epimers

O

‘453-j

Me0 (18b)

OMe

* both epimers

addition, related 00-and OS-phosphorothioates and some phosphonates and phosphonothioate esters were also characterized.lgAlthough these were prepared by essentially standard methods they have provided (see p. 105) a very convenient system for examining the behaviour of six-membered cyclic phosphate esters with nucleophiles. Solvolyses of Phosphoric Acid Derivatives.-There has been relatively little work reported on the solvolysis of simple phosphate esters. Instead, attention has been given to situations where intramolecularparticipation or other special features are likely to be important. Using a phosphodiesterase, it has been possible to measure directly the enthalpies of hydrolysis of ethylene phosphate, trimethylene phosphate, and diethyl phosphate (all as their sodium salts).2o As expected, that of the first was found to be appreciably more negative than the latter two. From a detailed comparison of the rates of aqueous hydrolysis of a very wide range of phosphate monoester monoanions it was found that there exists lo l7

J. E. Leffler and H. Jaffe, J. Org. Chem., 1973, 38, 2719. 0. I. Kolodyazhnyi, G. A. Kalyagin, and Y . G. Gololobov, Zhur. obshchei Khim., 1973, 43, 1859.

l8 lD

D. B. Cooper, T. D. Inch, and G . J. Lewis, J.C.S. Perkin I, 1974, 1043. D. B. Cooper, J. M. Harrison, T. D. Inch, and G. J. Lewis, J.C.S. Perkin I, 1974, 1049. J. M. Sturtevant, J. A. Gerlt, and F. H. Westheimer, J. Amer. Chem. SOC.,1973,95,8168.

Organophosphorus Chemistry

102

a good correlation of rate with both the second pKa of the acid and the chemical shift of the hydroxyl proton in ROH.21Although this adds little to a mechanistic understanding of the hydrolytic process it appears to be useful for predicting rates and hence assessing the importance of intramolecular catalysis effects. Thus, in the pH range 1-3, 2-chloropyridyl-3-methylphosphate (19) solvolysesfaster than expected ;moreover, loss of chloride ion, which accomTo panies the solvolysis, is considerably faster than from the parent

account for this it was suggested that hydrogen-bonding to chlorine assists attack of water at the 2-position, giving the intermediate (20), which is known to break down rapidly to inorganic phosphate. Catalysis of the hydrolysis of 0-phosphoryl threonine in the presence of pyridoxal is observed with CuII and VIV but not with other transition-metal ions; there is further rate enhancement when an organic base is added.23It seems clear that these two metal ions form a 1 : 1 complex (21) with the

(21)

M = Cu2+ or V 4 +

threonine-pyridoxal adduct, which undergoes a rate-determining basecatalysed elimination. Polyethylenimine catalyses the breakdown of pnitrophenyl phosphate in aqueous solutions of pH >6,24and the available evidence implies that nucleophilic attack by the free NH group of the catalyst is an important contributor. Y.Murakami and J. Sunamoto, J.C.S. Perkin II, 1973, 1235. Y.Masamuni, J. Sunamoto, and N. Kanamoto, Bull. Chem. Soc. Japan, 1973,46, 1730. ** Y. Murakami, H. Kondo, and A. E. Martell, J. Arner. Chem. Soc., 1973,95, 7138. es R. Fernandez-Prini and D. Turyn, J.C.S. Faraday I, 1973, 69, 1326. p1

Quinquevalent Phosphorus Acids

103

The oxidative hydrolysis of quinol phosphate (22) and its mono- and diAt pH 7-8 the methyl esters with aqueous periodate has been 0

\ /OR

V P \ 0 R

(22)

OH R = H o r Me

dianion proceeds at the fastest rate and probably involves a unimolecular elimination of PO;; at low pH the methyl esters react faster but the position of cleavage was not determined. No periodate ester intermediates could be detected, and it seems therefore probable that their formation is rate-limiting. Related studies on the naphthalene series (23) with a variety of oxidizing

OH (23)

agents (oxygen, iodine, periodate, FeIII) have shown 2 6 that the anions react faster than the free phenols, and that the rate is decreased when R is electronwithdrawing. This, too, is consistent with a rate-determining attack by the electrophile on the substrate.

(24)

Acid-catalysed hydrolysis of phosphoroguanidates (24) shows a bellIt appears that the shaped pH-rate profile with a maximum around pH most reactive species is the neutral zwitterion (25) (both the cation and monoanion forms ale a factor of lo4 less reactive), which undergoes a unimolecular elimination. On the basis of these results a tentative model for the *5

ze e7

R. J. Brooks, C. A. Bunton, and J. M. Hellyer, J . Org. Chem., 1973, 38, 2151. V. A. Batyuk, S. A. Bitko, and G. B. Sergeev, Kinetika i Kataliz, 1973, 14, 853 (Chem. Abs., 1973, 79, 136210). G. W. Allen and P. Haake, J. Amer. Chem. Soc., 1973, 95, 8080.

104

Organophosphorus Chemistry

action of creatine kinase was proposed. The acid-catalysed hydrolysis of hexamethylphosphoric triamide has also been examined, and from the values of AH* and AS* it has been suggested that loss of the first dimethylamine occurs from 0-protonated substrate whereas subsequent ones are lost from N-protonated species.28 In water at pH < 7.0 the hydrolysis of triethyl phosphate proceeds by water attack on the CH', group, and there is no acid catalysis observed up to 0.5 mol 1-l; in contrast, an acid-catalysedmechanism, A A L ~does , appear to operate in 35 % dio~an-water.~~ Hydrolysis of some dimethyl vinyl phosphates (26) by

R

acid in aqueous dioxan appears to follow the expected A s ~ 2mechanism.3o The related vinyl ester (27) is readily solvolysed by hydroperoxide ion, presumably by attack on phosphorus, but the reaction shows complex kinetics

(27)

owing to dimerization of the substrate.31 This last reaction is catalysed by the addition of acetone, but the mechanism of this catalysis is not yet clear. Rates of hydrolysis of the trimethyl esters (28) in aqueous alkali decrease in (MeO),P=X (28)

X = 0,S , or Se

the sequence P=Se> P=O > P-S whereas in aprotic solvents the relative order is P=Se>P=S>P=0.82 The decrease in relative reactivity of the P=O compound in protic solvents may be due to their ability to hydrogenbond. Alkoxide ions appear to attack the pyrophosphorothioate ester (29) a*

so

J. Y. Gal, J. P. Martinat, and T. Yvernault, Compt. rend., 1973, 277, C, 1105. E. P. Lyznicki, K. Oyama, and T. T. Tidwell, Canad. J. Chem., 1974,52, 1066. C. Triantaphylides, G. Peiffer, and R. Gester, Bull. Soc. chim. France, 1973, 1756. M. Marcantonatis and L. Genoud, Analyt. Chim. Acta, 1974, 68, 277. V. E. Bel'skii, N. N. Bezzubova, M. V. Efremova, and I. A. Nuretdinov, Zhur. obshchei Khim., 1973, 43, 1255.

Quinquevalent Phosphorus Acids

105

(29)

preferentially at the phosphoryl centre whereas thiolate anions attack preferentially at the thiophosphoryl centre.33Solvolysis of the cyclic ester (30) in ethanol gives, eventually, diethyl phosphate and the thioether (31).34

(31)

Some interesting stereochemical results have emerged from studies of nucleophilic displacements on 2-0x0- (and 2-thio-) 1,3,2-dioxaphosphorinan The degree of inversion of (32) was found to depend on the nature yH,Cl

I

Y (32) X = O o r S

both of the leaving group and of the incoming nucleophile, strongly basic nucleophiles and good leaving groups giving inversion whereas weakly basic nucleophiles and poor leaving groups gave predominant retention. In addition, added inorganic salts increased the degree of inversion. Similar conclusions were arrived at from the 4,6-glucose derivatives (18a).36It was suggested36that two distinct mechanisms operate (an s N 2 and a pseudorotation mechanism) but it is not clear whether the distinction between an sN2 process and one involving a phosphorane intermediate whose rate of breakdown is faster than its rate of pseudorotation is a useful one on current evidence. as

s6

B. Mlotkowska, Zeszyty Nauk. Politech. lodz. (Chem.), 1973, 163, (Chem. Abs., 1974, 80, 132388). M. Sasaki, H. Ohkawa, and M. Eto, J. Fac. Agric. Kyushu Univ., 1973, 17, 173, (Chem. Abs., 1973, 79, 42458). W. S. Wadsworth, J. Org. Chem., 1973, 38, 2921; W. S. Wadsworth, and Y.-G. Tsay, ibid., 1974, 39, 984. J. M. Harrison, T. D. Inch, and G. J. Lewis, J.C.S. Perkin I, 1974, 1053.

106

Organophosphorus Chemistry

A remarkable demonstration of the ease of formation of six-co-ordinate Pv species from four-co-ordinateprecursors is the o b ~ e r v a t i o nthat ~ ~ both phenyl phosphorodichloridateand the cyclic ester (33) give the salt (34) when treated

(34)

(33)

with catechol and triethylamine ;o-aminophenol behaves in a similar manner. The ready formation of compounds (34) does suggest that six-co-ordinate phosphorus intermediates may be more important in substitution reactions of phosphate and phosphonate derivatives than has hitherto been assumed. Reactions of Phosphoric Acid Derivatives.-Interest in HMPT both as a solvent and as a reactant continues. In this solvent &unsaturated carboxylic acids are reduced by lithium to mixtures of the saturated analogues and symmetrically substituted adipic acids; addition of lithium acetate gives reasonable yields of substituted glutaric acids, probably by initial metallation by lithium diethylamide38 (Scheme 2). Butyl-lithium, however, cleaves CO, H Li HMPT

CO, H

Li HMPT-LiOAc

Scheme 2

HMPT to the phosphonic amide derivative (35).3BThe blue colour produced on pulse radiolysis of HMPT, initially thought to be due to solvated electrons,

is now considered to be due to U.V. absorbance of an excited state (or, possibly, a decomposition Further studies on the behaviour of aliphatic amides in refluxing HMPT suggest that the initial intermediate is the nitrilium cation (36), whose sub37 38

39 40

T. Koizumi, Y. Watanabe, Y. Yoshida, and E. Yoshii, Tetrahedron Letters, 1974, 1075. G . P. Chiusoli and F. Gasparoni, Gazzetta, 1973, 103, 619. E. M. Kaiser, J. D. Petty, and L. E. Solter, J. Organometallic Chem., 1973, 61, C1. A. M. Koulkes-Pujo, L. Gilles, B. Lesigne, J. Sutton, and J. Y . Gal, J.C.S. Chem. Comm., 1974, 71.

Quinquevalent Phosphorus Acids

107

R’C-N sequent fate can give a variety of The formation of (37) from Nbenzylacetamide under these conditions may arise from rearrangement of (38). PhCH,CH,CN

PhCH,N=C=CH,

(38)

(37)

Of more practical interest is the observation that amides such as (39) are converted into a1kylpyridines (40) 4 2 under these conditions, since the generality

of this reaction and the accessibility of the starting materials amply compensate for the modest yields ( 1 5 4 % ) . The use of HMPT for replacing aromatic substituents with a dimethylamino-group has been extended 4 3 and similar reactions have been reported to occur with 2- and 4-pyrid0nes.~~ The nature of the products of oxidation of cyclophosphamide with Fenton’s reagent has been further investigated and it now appears that the crystalline isolable product is the dimer peroxide (41).45Both (41) and the hydroperoxide (ClCHzCH2),N

o\p,N(cH~cH2cl~,

\/ 0

0 ’

‘N

U

-

N’ O

- O (41)

‘ 0

U

undergo hydrolysis in aqueous solution to 4-hydroxycyclophosphamide, which itself readily eliminates a ~ r o l e i n and , ~ ~ it seems clear that the earlier 41 42

43 41

45

40

E. B. Pedersen and S . - 0 . Lawesson, Tetrahedron, 1973, 29, 4205. T. Frejd, E. B. Pedersen, and S.-0. Lawesson, Tetrahedron, 1973, 29, 4215. E. B. Pedersen, J. Perregard, and S . - 0 . Lawesson, Tetrahedron, 1973, 29, 4211. H. Vorbruggen, Synthesis, 1973, 301. A. Takamizawa, S. Matsumoto, and T. Iwata, Tetrahedron Letters, 1974, 517; R. F. Struck, M. C. Thorpe, W. C . Coburn, and W. R. Laster, J . Amer. Chem. SOC., 1974,96, 313. J. Van der Steen, E. C. Timmer, J. G. Westra, and C. Benkhuysen, J . Amer. Chem. SOC., 1973, 95, 7535.

Organophosphorus Chemistry

108

conflicting reports arose from the ready interconvertibility of these products under the oxidation conditions. The reaction of hydroxyl radicals with glycol phosphates has been examined by e.~.r.,~' and it was observed that, when the radical centre resulting from initial hydrogen abstraction was /3 to the phosphate group, rapid elimination of the latter occurred. A free-radical mechanism involving hydrogen abstraction must also occur in the thermal reaction of olefins with esters of t-butylperoxyphosphoric acid to give the allylic phosphates (42).48 YP(OR), /O

AIkylation of thiophosphate dianion (43; R = HO) with diazomethane gives both S- and O-methylation in the ratio of 4 : 1 ; the analogous phosphonothioate (43;R = alkyl) gives a similar ratio.49 In its reaction with 0

II

R-P-0-

s(43)

R = HOoralkyl

1-diazopropan-2-one, however, which presumably has much more S N ~ character, only S-alkylation was observed. Similarly, ring-opening of substituted oxetans with 00-dialkyl phosphorodithioic acids occurs at the less substituted of positions 2 or 4, implying that an s N 2 mechanism is followed here also.6oIn contrast, studies on the addition of 00-dialkyl phosphate and phosphorothioates to electron-rich olefins (44) suggest that initial proton

(44) X, Y = 0,S, or N

transfer gives an intimate ion pair which collapses to 47

49

Rate

A. Samuni and P. Neta, J . Phys. Chem., 1973, 77, 2425. G. Sosnovsky, G. Karas, and D. J. Rawlinson, Phosphorus, 1973, 3, 87. T. A. Mastryukova, L. S. Butorina, and M. I. Kabachnik, Zhur. obshchei Khim., 1973, 43, 2083. B. A. Arbuzov, 0. N. Nuretdinova, F. Guseva, R. G. Gainullina, and L. Z. Nikonova, Izvest. Akad. Nauk S.S.S.R.,Ser. khim., 1973, 2342 (Chem. Abs., 1974, 80, 36929). P. G . Le Griis, R. L. Dyer, P. J. Clifford, and C. D. Hall, J.C.S. Perkin II, 1973, 2064.

Quinquevalent Phosphorus Acids

109

measurements have also been made on the addition of 00-diethyl phos= phorodithioic acid to a series of electron-deficient olefins (45).52

/CO& RC,H,CH=C,

Dimethyl 4-methoxybenzyl phosphate (46) is converted by treatment with butyl-lithium into the hydroxyphosphonate ester (47).63A similar reaction has

(47)

OH

been reported earlier for cyclic phosphinate esters, and the reverse reaction, which is intramolecular, is well established. It would be interesting to know whether this reaction of (46) is intramolecular or whether it involves initial dissociation of the anion to the substituted benzaldehyde and dimethyl phosphonate anion followed by recombination. In this connection it has been observed that whereas (48; R = NMe,) gives a stable carbanion with butyllithium the corresponding ester (48; R = EtO) undergoes elimination to the imine and diethyl phosphonate anion.54

N-EHPh

I

Me The reduction of aryl diethyl phosphates to aromatic hydrocarbons (first reported several years ago) has been investigated further and found to be a convenient and reasonably general procedure giving consistently high yields.ti Reduction of the phosphorodithioate ester (49)with zinc and acid is reported to give a mixture of phosphate and phosphinothioite esters together with some s8

A. N. Pudovik, R. A. Cherkasov, and G . A. Kutyrev, Zhur. ubshchei Khim., 1973, 43, 1466. G . Sturtz and B. Corbel, Cumpt. rend., 1973, 276, C, 1807. P. Savignac and Y. Leroux, J. Organometallic Cheni., 1973, 57, C47. R. A. Rossi and J. F. Bunnett, J. Org. Chent., 1973, 38, 2314.

110

Organophosphorus Chemistry

(49) 0 phosphine.5 6 Diethyl NN-dibromophosphoramidateappears to be reduced by zinc to diethoxyphosphorylnitrene (50),57since when the reduction is carried out in benzene solution the anilide (51) is isolated.

'NHPh (51)

The sulphenyl chloride (52) reacts with strongly activated aromatic rings to give S-aryl phosphorothioateesters; the selenium analogue behaves similarly.5 8

(52) X = S or Se

Secondary amines cleave the disulphide (53) to the NN-dialkylsulphenamide derivative (54) but tertiary amines under similar conditions give only products from dealkylation.59

(54) 56 s1 68

b-

I

0-

M. Y . Lee, Yakhalc Hoeji, 1972, 16, 47 (Chem. Abs., 1974, 80, 14676). A. Zwierzak and S. Zawadzki, Tetrahedron, 1973, 29, 3899. A. Markowska and W. Buchowiecki, Bull. Acad. polon. Sci., Se'r. Sci. chirn., 1973, 21, 455 (Chem. Abs., 1973, 79, 115245). B. A. Khaskin, N. A. Torgasheva, N. N. Mel'nikov, and G . S. Supin, Zhirr. obshchci Khim.,1974, 44, 224.

Quinquevalent Phosphorus Acids

111

Trimethyl phosphate has been suggested as a coavenient reagent for esterifying hindered carboxylic acids and was used in this manner to convert 1,l’binaphthyl-8-carboxylic acid into its methyl ester.so Trialkyl phosphates have also been investigated as reagents for alkylating heterocyclic nitrogen bases.g 2 Phosphonic and Phosphinic Acids and Derivatives

Synthetic Methods.-Direct routes to phosphonic acid derivatives from olefins and phosphorus halides continue to be explored. In the presence of oxygen, phosphorus tribromide reacts with olefins by a radical mechanism in a manner analogous to the corresponding chloride, giving 2-bromoalkyl-lphosphonyl dibromideses2The reaction of phosphorus trichloride and perchloryl fluoride with hex-1-ene gives moderate yields of ( 5 9 , the direction of

addition suggesting that an ionic mechanism involving attack on the olefin by an electrophilic phosphorus species operates here. 6 3 Thiophosphoryl chloride in the presence of aluminium chloride reacts with ethylene to give modest yields of (56) but phosphoryl chloride is inert under these conditions.04The CH,= CH, + PSCl,

AICI,

CH,=CHPSCL, (56)

phosphonic dichloride obtained from butadiene and phosphorus pentachloride followed by sulphur dioxide has been shown to possess the E configuration (57).65

HYcH2*c4

ClCH,+h (57)

Dichloroacetylene undergoes a doiible Arbusov-type reaction with trialkyl phosphites, giving the ethynyldiphosphonic ester (58).s6 The ready availability 6o 61

8e

43

64

R6

66

M. M. Harris and P. K . Patel, Chem. and I d . , 1973, 1802. K. Yaniauchi and M. Kinoshita, J.C.S. Perkin I , 1973, 2506. Y . Okamoto and H. Sakurai, Chern. Letters, 1973, 599. S. V. Fridland, N. V. Dmitrieva, I. V. Vigalok, T. V. Zykova, and R. A. Salakhutdinov, Zhur. obshchei Kliim., 1973, 43, 572, 1494. Y . A. Levin and R. 1. Pyrkin, Zhur. obshchei Khim., 1973, 43, 281. V. I. Zakharov, A. V. Dogadina, L. N. Mashlyakovskii, B. I. Ionin, and A. A. Petrov, Zhur. obshchei Khim.,1974, 44, 98. S. V. Kruglov, V. M. Ignat’ev, B. I. Ionin, and A. A. Petrov, Zhur. obshchci Khim., 1973, 43, 1480.

Organophosphorus Chemistry

112 0

0

II II (EtO),PC--CP(OEt), (58)

of acetylenic phosphonate esters suggests that they may prove convenient routes to &ketophosphonate esters (59), into which they are converted by RC=C-PO(OEt),

+

_j.

//O R,C=CHP(OEt),

R"H,

treatment with a primary alkylamine followed by acid.s7 Reaction of propargyl alcohols with phosphorus tribromide may, depending on the conditions, give (60) 0r1(6l).~~

Derivatives of aziridinyl-l-phosphonic acid esters have been prepared by reaction of primary amines with the bromo-ester (62);69 unfortunately these //O

MeCH=CBrP(OEt), (62)

RNH,

/p

MeCH-CHP(OEt),

'N'

I

'' M. S. Chattha and A. M. Aguiar, J. Org. Chem., 1973, 38, 2908. W.

a*

R. C.Elder, L. R. Florian, E. R. Kennedy, and R. S. Macomber, J. Org. Chem., 1973, 38, 4177. K. D.Berlin and S. Rengaraju, Proc. OkZahoma Acad. Sci., 1973, 53, 73 (Chem. Abs., 1973, 79, 136918).

Quinquevalent Phosphorus Acids

113

esters could not be hydrolysed without cleavage of the three-membered ring. 1-Aminoalkylphosphonic acid esters (63) are conveniently prepared by addition of a dialkyl phosphite to azines followed by hydr~genation.~~ Another

R' NH,

XP(OEt)%

R2

/O

general route to these compounds is by hypobromite on The related 1-ureidoalkylphosphonates(65) are formed by treatment of an appropriate

-

(R'O),P(O)CHR* NHCONH, (65)

aldehyde with urea and a trialkyl phosphite in the presence of acid.7aAddition of trimethyl phosphite to l-acetamidoacrylicacid has been used to prepare the P-aminoalkylphosphonic acid derivative (66).78

Esters of 1-alkoxyvinylphosphonicacid (67) may be obtained in one step by reaction of a trialkyl orthoacetate with trialkyl phosphite and phosphorus

t r i ~ h l o r i d e .The ~ ~ preparative route to l-ethoxycarbonylvinylphosphonates (68) by aldol-type condensation of triethyl phosphonoacetate with an appropriate carbonyl compound has been improved using titanium tetrachloridetriethylamine 7 5 as condensing agent. 7o

71

'8

74

75

J. Rachon and C.Wasielewski, 2. Chem., 1973, 13, 254. M. Soroka and P. Mastalerz, Tetrahedron Letters, 1973, 5201. G. H. Birum, J . Org. Chem., 1974,39,209. M. K.:Rho and Y . J. Kim, Daehan Hwahak Hwoejee, 1973,17,135 (Chem. Abs., 1973, 79, 5552). P. Golborn, Synthesis, 1973, 547. W. Lehnert, Tetrahedron, 1974,30, 301.

114

Organophosphorus Chemistry

The sulphoxide derivative (69) cannot be obtained by phosphorylation of the sulphoxide but has been prepared from the corresponding sulphide by oxidation with periodic acid.'"

Solvolyses of Phosphonic and Phosphinic Esters.-The full paper has appeared on the alkaline hydrolysis of some phosphinic esters for which there is kinetic evidence of a phosphorane intermediate (reported last year).77It was observed that the phosphetan (70) hydrolysed faster than acyclic analogues, and this is

consistent with the view that here ring strain assists the formation of the phosphorane intermediate. Acid hydrolysis rates of some methyl esters of arylmethylphosphinic acids have been reported but no strikingly novel features have yet emerged.78 Acid hydrolysis of N-arylphosphinamides (71) appears, in general, to proceed by an A2 mechanism, although some support for an A1 mechanism was noted

when R = Ar.79Thus when R = Me it was found that methanolysis proceeded with inversion at phosphorus, while the relative rates of a series with varying R suggest that the steric effect of R is much more important than its ability to stabilize a developing phosphinylium In contrast to the corresponding ester, the dimethylamide (72) hydrolysed in acid lo3 times more slowly than comparable acyclic analogues, suggesting that phosphoranes are not intermediates and that a direct displacement mechanism probably 76

M. Mikolajczyk and A. Zatorski, Synthesis, 1973, 669.

77

R.D. Cook, C. E. Diebert, W. Schwarz, P. C. Turley, and P. Haake,J. Amer. Chern. SOC.,

78

1973, 95, 8088. .I.F. Bunnett, J. 0. Edwards, D. V. Wells, H. J. Brass, and R. Curci, J. Org. Client., 1973,38, 2703.

7y

D. A. Tyssee, L. P. Bausher, and P. Haake, J. Amcr. Chern. Soc., 1973, 95, 8066. M. J. P. Harger, J.C.S. Chem. Cornin., 1973, 774.

115

Qisinqueualent Phosphorus Acids

operates.s1Under alkaline conditions a small amount of l 8 0 exchange occurs during the hydrolysis of these amides but the rate is considerably slower than that of loss of amine. The effect of cycloamylase on the hydrolysis of several diary1 methylphosphonates in the pH range 5-11 appears to be due to an initial nucleophilic attack binding the phosphonyl group to the carbohydrate followed by a fast intramolecular nucleophilic attack by an adjacent hydroxy-group expelling a second mole of phenol.s2 Under weakly acid condition intramolecular catalysis of the hydrolysis of (73) occurs, giving stepwise elimination of both OH

0

CO,H

CO, H

0

0

(73)

ethoxy-groups by P-0 cleavage.83Similarly, in basic solution, attack of the oxime hydroxyl on phosphorus occurs in (74), giving migration of the phosphinyl group to give ( 7 3 , which undergoes a Lossen The

Ar

Relativerates: R' = R2 = Et 1 R' = EtO, R2 = Et 10 R' = R' = EtO 140

rate increases observed on replacement of Et by EtO in R1and R2may, if the initial attack is reversible, be plausibly attributed to facilitation of the neces-

83

T. Koizumi and P. Haake, J. Amer. Chem. SOC.,1973, 95, 8073. H. J. Brass and M. L. Bender, J . Amer. Chem. SOC.,1973, 95, 5391. J. P. J. Van der Holst, C. Van Hooidonk, and H, Kienhuis, Rec. Trau. chim.,1974, 93, 40. J. I. G. Cadogan, D. T. Eastlick, J. A. Challis, and A. Cooper, J.C.S. Perkin 11, 1973, 1798.

dl

5

Organophosphorus Chemistry

116

sary pseudorotations in the intermediate phosphorane, as a consequence of the higher apicophilicity of the ethoxy-group. Although the dianion of 2-chloroethylphosphonic acid (76) undergoes a

No

CICH2CH,P-O-

(76)

pH9-12

CH,=CH,

+ C1- + HFQ; (95%)

'0-

+. HOCH,CH,P //O -0'

(5%)

'0rapid elimination in solution, the solid disodium salt may be prepared using to elimination of inorganic phosphate. hydrocarbon ~ ~ I v e n tIn s . addition ~~ from the dianion in aqueous solution it has been found that small amounts (ca. 5 % ) of 2-hydroxyethylphosphonic acid are formed in the pH range 9-12.8s In view of the poor nucIeophilicity of water to saturated carbon it may possibly be that this arises by intramolecular nucleophilic participation,.

n

O-P=O

I

0-

(77) giving an unstable oxaphosphetan intermediate (77). Another facile #Ielimination of this type is provided by the monosodium salt of propan-2-one1-phosphonic acid (78), which gives acetone and sodium polyphosphate a t 150 "C - possibly via a cyclic transition 0

Ho

& L O

-

15ooc

1 t

(PO,),"'

O\

(78)

Some further intriguing results have been reported in connection with nucleophilic displacements on OS-esters of phosphonothioic acids.88From measurements of the rates of exchange and racemization of (79) it was shown that if it is assumed that the intermediate (80) with S apical does not survive long enough to pseudorotate, then, contrary to some earlier suggestions, this process is favoured by a factor of 5 over the alternative mode of attack giving (81). Methoxide attack on the cyclic OS-phosphonothioateesters (8%) gives P- 0 fission with inversion of configllrationBgwhereas the corresponding

87

G. K. Fedorova, L. G. Anan'eva, I. M. Kononenko, L. I. Maksyutina, and A. V. Kirsanov, Zhur. obshchei Khim., 1973'43, 538. B. G. Audley and B. L. Archer, Chem. and fnd., 1973, 634. R. Kluger, J. Org. Chem., 1973, 38, 2721. K. E. DeBruin and D. M. Johnson, J. Amer. Chem. SOC.,1973,95,7921. D. B. Cooper, J. M. Harrison, T. D. Inch, and G . J. Lewis, J.C.S. Perkin I, 1974, 1058.

117

Quinquevalent Phosphorus Acids

-

SMe Ph-P,

I _,..oI OMe

OCD,

OMe

(82)a; R = alkyl; X,Y = 0,s b; R = alkoxy; X , Y = 0 , s

phosphorothioate (82b) gives P- S fission, probably with retention. It seems, from recent studies on phosphoranes, that part at least of the reason for these and earlier observations on the anomalous behaviour of such esters lies in the very similar apicophilicities of RO and RS groups. Hence relatively small structural variations may be sufficient to direct the configuration of the firstformed phosphorane, whose subsequent fate is determined by the relative rates of pseudorotation/loss of one ligand. Rates of solvolysis of a series of phosphinic and thiophosphinic chlorides in aqueous acetone mixtures have been determined.O0 It would appear that the rates show a second-order dependence with respect to water concentration, but whether this is merely a medium effect or whether it represents a general basecatalysed process is not clear. The solvolysis of the chloride (83) is catalysed by silver ion, giving inversions at phosphorus with a high degree of stereospecificity.

%I

EtO' (83)

Hydrolysis of diethyl benzoylphosphonate (84) proceeds by C- P cleavage in both phosphate and imidazole buffers. The rates in the two buffers are so I'

A. A. Neimysheva, M. V. Ermolaeva, and I. L. Knunyants, Zhur. obshchei Khim., 1973, 43, 2608. W. J. Stec, Biiii. Acad. poion. Sci., Skr. Sci. chim., 1973, 21, 709 (Chem. Abs., 1974, 80,

36 606).

118

Organophosphorus Chemistry

comparable despite the very different nucleophilicities, and it therefore seems probable that a general base-catalysis mechanism operates.92 Reactions of Phosphonic and Phosphinic Acid Derivatives.-The products (85) and (86) obtained by the reduction of phosphonic dichlorides and their P=S analogues with magnesium in tetrahydrofuran in the presence of a trapping agent (benzil or diethyl disulphide) are explicable in terms of an intermediate

k'4

Mg-THF*

[ RP=X]

PhC=CPh

R

PhC=CPh

o

--+

P h C E C P h + RP,HX

/

R' X '

0-

0-

(87). However, it is possible that they arise by initial reduction of the trapping agent followed by reaction of the products with unreduced chloride.83The formation of small amounts of diphenylacetylenefrom the reductions carried out in the presence of benzil may result from an elimination from the dianion (88). The lithium derivative (89) has been claimed to be an excellent reagent for +

/p

(EtO), P,

BrxBr -"x"'

'CH, Li (89)

the monodebromination of gem-dibroniocyclopropanes.v4 Butyl-lithium reacts with diethyl trichloromethylphosphonate at low temperature to give

O9

s4

S . Andreae and W. Jugelt, Z . Chem., 1973, 13, 136. M. Yoshifugi, S. Nakayama, R. Okazaki, and N. Inamoto, J.C.S. Perkk I, 1973, 2065, 2069. K. Oshimo, T. Shirafuji, H. Yamamoto, and H. Nozaki, Bull. Chem. Suc. Jupan, 1973, 46, 1233.

119

Quinquevalent Phosphorus Acids

(90).9 5 Under similar conditions the epoxyphosphonate ester (91) undergoes ring-opening.g6 Pure alkali-metal salts (93) of diethyl phosphonoacetone have CCl,PO(OEt),

BuLi

LiCCJPO(OEt), (90)

(93)

been pre~ared.~' In the solid state they exist as cis-enolates but in solution an equilibrium exists between the cis- and trans-enolates and the C-metallated derivative. The dianion of diethyl phosphonoacetone has also been prepared for use in synthesis by treatment of the sodium salt in tetrahydrofuran with butyl-lithi~m.~~ Further studies have been reported on a-phosphonyl carbenes. Under irradiation, (94) (from the corresponding diazo-compound) is in equilibrium

\

R2

\

RZ

(97) 95 g6 97

D. Seyferth and R. S. Marmor, J. Organometallic Chem., 1973, 59, 237. A. P. Kakov and A. V. Alekseev, Zhur. obshchei Khim., 1973,43, 276. G. Petrov, I. Velinov, and M. Kirilov, Monatslz., 1973, 104, 1301. P. A. Grieco and R. S. Finkelhor, J. Org. Chem., 1973, 38, 2909.

120

Organophosphorus Chemistry

with the cyclopropen-l-ylphosphonateester (95);99 the allenic compound (96) is also produced and probably results from a thermal insertion reaction of (94). When R1or R2 = Ph, intramolecular cyclization is observed, giving the indene (97). Nitration of benzyl- and 2-phenylethyl-phosphonicacids under the usual conditions gives, as expected, the u- and p-nitro-derivatives.lO0 Diesters of benzylphosphonic acid may be alkylated at the benzylic position by treatment with strong base and alkyl halide;lo1mercuric acetate, however, cleaves the C-P bond, giving (98) lo8and benzyl acetate. The related phosphinate (99) is PhCH,PO(OR), (98)

+ Hg(OAc),

-

PhCH,OAc

+ (RO),P,

/O

'HgOAc

converted by base into the novel dibenzocyclo-octatrienephosphinic ester (100) - possibly through dimerization of an intermediatequinodimethide(l01) and subsequent elimination.lo3

(101)

Acetylphosphonate diesters undergo an aldol-type condensation with diazoacetic ester to give (102).104 Another novel substituted phosphonate ester OH

PO(0Et 1,

A. Hartmann, W. Welter, and M. Regitz, Tetrahedron Letters, 1974, 1835. T. A. Modro and A. Piekos, Tetrahedron, 1973, 29, 2561. I o l V. Lachkova and M. Kirilov, Annalen, 1974, 496. l a ' W. I. Awad, M. El-Deek, and E. El-Sawi, Tetrahedron Letters, 1973, 4663. lo* T. H. Chan and K. T. Nwe, Tetrahedron Letters, 1973, 3601. A. N. Pudovik, R. D. Gareev, A. B. Remizov, A. V. Aganov, G. I. Evstaf'ev, and S. E. Shtil'man, Zhur. obshchei Khim., 1973,43, 559. OD

loo

Quinquevalent Phosphorus Acids

121

reported is the isocyanide (103) formed by dehydration of the corresponding formamide.lo6With aldehydes and ketones in the presence of base, (103) give cycloaddition products (104).

(104)

Dithiophosphinic anhydrides (105) are formed from the parent acid by reaction with nitriles.106The cyclic perthiophosphinic anhydrides (106) react

S

S

&P<

+ PhCN

It

It

R,P-S-PR,

I_+_

S

+ %C4 -+

S

RP-S-S-S-S-PR It

ti

I

I

c1 (106)

Cl (107)

with disulphur dichloride to give (107).107In the reaction of sulphoxides with phosphonodichloridates, giving pyrophosphonic acids, the order of reactivity of a series of sulphoxides was Me,SO > PriSO > MeSOPh > Ph,SO. lo8 Reaction of the cyclicthiophosphonic anhydride (108) with dialkyl cyanamides gives (109) and not the corresponding P T= 0 compound.loo

(108)

(109)

Miscellaneous-There have been several studies (mainly by i.r. spectra and dipole measurements) of donor complexes formed by derivatives of various U. Schollkopf, R. Schroder, and D. Stafforst, Annalen, 1974, 44. A. N. Pudovik, R. A. Cherkasov, T. M. Sudakova, and G. I. Evstaf'ev, Doklady Akad. Nauk S.S.S.R., 1973, 211, 113 (Chem. Abs., 1973,79,92330). l o ' E. Fluck, F. Ibaiiez, and H. Binder, 2 .anorg. Chern., 1973, 397, 147. l o 8 M. A. Ruveda, E. N. Zerba, and E. M. De Moutier Aldao, Anales Asoc. quim. argentina, 1973, 61, 233 (Chem. Abs., 1974, 80, 83 140). l o S L. Maier, Helv. Chirn. Acta, 1973, 56, 2490.

lo5

122

Organophosphorus Chemistry

P-acids, including those between (1 10) and nitric acid and phenols,11o phosphonic chlorides and phenols,ll1 and trialkyl phosphates and propan-2-01. 112

1.r. studies have also shown that in non-polar solvents dithiophosphinicacids form cyclic hydrogen-bonded dimers in addition to intramolecular hydrogenbonding.l13 The exchange of fluorine by chlorine in compounds (111) has been studied

(111) X = S, Se, 0,or lone pair

by lH n.m.r. and it was observed that the equilibrium in favour of the P-F compound decreased in the series X = O>S>Se% lone pair.l14 Other n.m.r. studies have shown that boron trifluoride co-ordinates preferentially to equatorial P= 0 groups in 2-0x0-1,3,2-dioxaphosphorinans.115 Radical species formed by y-irradiation of phenylphosphonic dichloride and the P=S analogue have been studied by e.s.r.,l16 as has the radical (1l2).ll7 Several spin-labelled derivatives of phosphinic acid incorporating the stable radical (1 13) have also been reported.ll*,119

0

II

Ph-r-OH

ll0

11=

11*

114

116

116

11' 118

ll@

B. N. Laskorin, V. V. Yashkin, E. P. Buchikin, L. I. Sokalskaya, and V. I. Medvedev, Teor. i eksp. Khim., 1973, 9, 245 (Chem. Abs., 1973, 79, 31 326). 0. A. Raevskii, Y. A. Donskaya, A. Y. Kessel, L. V. Nesterov, and A. N. Pudovik, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 536 (Chem. Abs., 1973, 79, 4523). W. Waclawek and L. Adamowski, Bull. Acad. polon. Sci., S&. Sci. chim., 1973, 21, 233 R. R. Shagidullin, I. P. Lipatova, 0. A. Raevskii, L. T. Vachugova, R. A. Cherkasov, F. G. Khalitov, and S. A. Samartseva, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 541 (Chent. Abs., 1973, 79, 4524). J. G. Riess, J.-C. Elkaim, and A. Thoumas, Phosphorus, 1973, 3, 103. J. P. Majoral, C. Bergounhou, J. Navech, P. C. Maria, L. Elegant, and M. Azzaro, Bull. SOC.chim. France, 1973, 3142. S. P. Mishra and M. C. R. Symons, J.C.S. Dalton, 1973, 1494. S. P. Mishra and M. C. R. Symons, Tetrahedron Letters, 1973, 4919. G. Sosnovsky, M. Konieczny, and H. L. Lin, Phosphorus, 1973, 2, 241. E. G. Rozantsev, V. I. Suskina, Y. A. Ivanov, and B. 1. Kaspruk, Izvest. Akad. Ncruk S.S.S.R., Ser. khim., 1973, 1327 (Chem. Abs., 1973, 79, 105352).

Quinquevalent Phosphorus Acids

123

There have appeared several studies on the conformation of acyclic phosphonic and phosphinic esters 120-122 and some calculations on the equilibrium conformation of a series of enol phosphates have been reported.123Crystal structure determinationson the very reactive cyclic phosphate (1 ;R1 = MeO) have shown that the five-membered ring is almost planar and that the carbonyl bond is short.124

P. E. Clark, K. D. Berlin, J. Mosbo, and J. G. Verkade, Phosphorus, 1973, 2, 265. Y. Y. Borovikov, Y. P. Egorov, A. M. Pinchuk, and T. A. Khimchenko, Zhur. obshchei Khim., 1973, 43, 2476. l a r A. B. Remizov, I. Y. Kuramshin, A. V. Aganov, and G. G. Butenko, Doklady Akad. Nauk S.S.S.R., 1973,208, 1118 (Chem. Abs., 1973,78, 147228). l a 3 E. Gaydou, J . Chim. phys., 1973,70, 1199 (Chem. Abs., 1973,79, 145748). G. D. Smith, C. N. Caughlin, F. Ramirez, S. L. GIaser, and P. Stern, J . Amer. Chem. SOC.,1974, 96, 2698. 120 lal

7 Phosphates and Phosphonates of Biochemical Interest BY

D. W. HUTCHINSON

1 Introduction Regular readers of this series of Reports will notice that this Chapter has undergone fission. This is principally due to the ever increasing number of papers on organophosphorus compounds in the chemical and biochemical literature. As a consequence, topics concerning nucleotides and nucleic acids are discussed in Chapter 8 while other topics relating to the reactions of biochemically interesting phosphorus compounds remain in this chapter. The most interesting developments in this field during the past year have been the increasing use of affinity chromatography for the purification of enzymes and the use of lSC and 31P n.m.r. for the study of the properties of enzymes in solution. Specific active site reagents, which are often phosphate esters, have also been popular tools for obtaining data on the shape and reactivity of enzymes. Among the many recent books and reviews are the latest volume of the third edition of ‘The Enzymes’,l a medically oriented text on calcium and phosphorus metabolismY2and a review on the bio-organic chemistry of phosph~rus.~ The last is not, however, as far-reaching as its title would suggest but is confined to phosphate ester hydrolysis.

2 Coenzymes and Cofactors Nicotinamide Nuc1eotides.-The reaction between phosphorothioates and disilver salts of phosphoric acids has been used to synthesize FAD, UDPGlc, and UDPGal in high yield.4 An advantage of this method is that by-products such as symmetrical pyrophosphates are not formed. Simple procedures for the preparation of NMN+ by chemical or enzymic methods have been reported and although the phosphorylating agent ‘metaphosphoric acid’ used in the chemical phosphorylation of nicotinamide 2’,3’-O-isopropylidene ribofuranoside is relatively unsophisticated, the synthesis can be carried out on a large scale with moderate yields. The stereo1

‘The Enzymes’, ed. P. D. Boyer, 3rd Edn., Academic Press, New York, 1973, Vol. 8.

* J. T. Irving, ‘Calcium and Phosphorus Metabolism’, Academic Press, New York, 1973. a

R. Singleton, jun., J . Chem. Educ., 1973, 50, 538. I. Nakagawa and T. Hata, Bull. Chem. SOC. Japan, 1973,46, 3275. R. Jeck, P. Heik, and C. Woenckhaus, F.E.B.S. Letters, 1974, 42, 161.

3 24

Phosphates and Phosphonates of Biochemical Interest

125

chemistry of the reduction of NAD+ and a number of analogues containing 3-substituted pyridine rings [e.g. (l)] is identical.6 These analogues are readily An alkylated analogue (2) available with the aid of pyridine transglyc~sidase.~ of NAD+can be prepared by the action of hydrochloric acid on 3-diazoacetylpyridine adenine dinucleotide but not directly by transglycosidation as (2) inactivates the transglycosidase.Although (2) is active as a hydrogen acceptor with glutamate dehydrogenasewith no detectable inhibition of enzyme activity, it is inactive as an acceptor with yeast alcohol dehydrogenase and inhibits the enzyme. It is suggested that (2) may be of use for the affinity labelling of some dehydrogenases.

R R = adenosine4'-pyrophosphoryl-S-@-D-ribofuranosyl)

I

CH,CH,OH

The drug most commonly used to treat Trichomonas vaginalis and some entamoebal infections, 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole[Flagyl, (3)] can also produce an aversion to ethanol in patients. It has now been shownBthat while (3) will displace the nicotinamide moiety of NADf or NADP+ in the presence of pyridine transglycosidase to produce new nucleotides, there is no reaction between (3) and NADH. lo It is not, however, believed that the toxicity towards anaerobic organisms is due to the new adenosine pyrophosphates derived from (3). Two new derivatives of NAD+have been prepared l1, l 2for the purification of dehydrogenasesby affinity chromatography. In these derivatives the adenine residue is joined at the 6-position to an insoluble support by means of a spacer a

J. F. Biellmann, C. G. Hirth, M. J. Jung, N. Rosenheimer, and A. D. Wrixon, European J. Biochem., 1974, 41, 5 17. N. 0. Kaplan, Methods in Enzymol., 1955, 2, 660. J. F. Biellmann, G. Branland, B. Y.Foucaud, and M. J. Jung, F.E.B.S. Letters, 1974,40, 29.

lo

l1

G . H. Coombs and B. R. Rabin, F.E.B.S. Letters, 1974, 42, 231. G . H. Coombs and B. R. Rabin, F.E.B.S. Letters, 1974, 42, 105. M. Lindberg, P. 0. Larsson, and K. Mosbach, European J. Biochem., 1973, 40, 187.

Organophosphorus Chemistry

126

arm. In one case the arm is obtained by chemically modifying the adenine residue of NAD+,lland in the other the synthesis of N6-(6-aminohexyl)-AMP is coupled with NMN+ using trifluoroacetic anhydride.12 Coenzyme A.--Coenzyme A when immobilized on cyanogen bromideactivated Sepharose has a strong affinity for a specific protein from a number of bacteria, notably Sarcina 2utea.l8 By covalently linking a dialysed extract from this micro-organism to cyanogenbromide-Sepharose, a chromatographic column can be obtained which will purify crude CoA to a high degree. The enzymic synthesis of CoA from dephospho-CoA and ATP has been adapted for the preparation of the 32P-labelledmaterial. l 4 Pyridoxal.-Oxidation of o-hydroxypyridoxal methyl hemiacetal (4) by manganese dioxide followed by phosphorylation of the intermediate dialdehyde with polyphosphoric acid affords (5) l5 (Scheme 1). The latter should be a useful reagent for affinity labelling enzymes requiring pyridoxal phosphate as cofactor since there are two reactive aldehydegroups in the molecule. Pyridoxal phosphate itself can be used as a probe for the investigation of the active sites of enzymes because of its reaction with lysine residues l6,l7 and its ability to act as a sensitizer for the photo-oxidation of neighbouring amino-acids, e.g. histidine.l6 ,OH

,oPo,H,

H*$oH

i, ii

HOCH,

OHC (4 1

(5 1

Reagents: i, MnO,-H+; ii, PPA.

Scheme 1

The non-enzymic dephosphorylation of O-phosphorothreonine which is brought about by pyridoxal in aqueous media has been investigated and a mechanism for the reaction has been propoSedla (Scheme 2). Copper(rI) and oxovanadium(rv)ions exert a strong catalyticeffect and the dephosphorylation proceeds with C-0 fission. The initial formation of a Schiff base may occur, followed by the loss of a proton from the a-carbon atom of the threonine. O-Phosphoro-a-methylserine, which does not possess an a-proton, does not dephosphorylate readily in aqueous solution. l2

D. B. Craven, M. J. Harvey, and P. D. G. Dean, F.E.B.S. Letters, 1974, 38, 320.

l5

Y.Matuo, T. Tosa, and I. Chibata, Biochim. Biophys. Acta, 1974, 338, 520. E. A. Siess and 0. H. Wieland, Analyt. Biochem., 1974, 58, 310. A. Pocker, J. Org. Chem., 1973, 38, 4295.

l7

P. Greenwell, S. L. Jewett, and G. R. Start, J. Biof. Chem., 1973, 248, 5994. A. Venegas, J. Martial, and P. Valenzuela, Biochem. Biophys. Res. Comm., 1973, 55,

lo

lP

1053.

Y. Murakami, H. Kondo, and A. E. Martell, J. Amer. Cliem. SOC.,1973, 95, 7138.

Phosphates and Phosphonates of Biochemical Interest

127 Me H

q

H,O,P-0-C-C-C

//

CHO HO&H20H\ HO,CCHCH(Me)OPO,H,

I

NH2

I JI I I H N

+ Me

pyridoxal + CH,CH,CCOi

II

NH

NH, + CH,CH,COCO; Scheme 2

+PPi

ii ,CO,, phosphoenolpyruvate carboxytransphosphorylase

Scheme 3

\o

/ "*cu

HC

Reagents : i, H', phosphoe nolpy ruva t e c arhox y t rinsp hosphorylnse:

//O

\

128

Organophosphorus Chemistry

Ph~sphoenolpyruvate.-Phosphoenolpyruvate carboxytransphosphorylasecatalyses two separate conversions of phosphoenolpyruvate (6) (Scheme 3). In the absence of carbon dioxide pyruvate and inorganic pyrophosphate may be formed; enzymic dephosphoiylation of (6) to enolpyruvate is probably followed by the non-enzymic protonation of the latter giving rise to pyruvate.lS In the presence of carbon dioxide, the carboxytransphosphorylase converts (6) into oxalacetate. In this case this reaction is stereospecific and the carbon dioxide adds on to only one side of ( 0 . 2 0 A quinquecovalent pyrophosphoenolpyruvate intermediate (7) is proposed in this reaction and P--0. fission occurs with no incorporation of l 8 0 into the reaction products when the reaction is carried out in H,1*0. A similar lack of incorporation of isotope from solvent into products has been observed in the reaction catalysed by phosphoenolpyruvate carboxykinase2 1 (Scheme 4), and it is thought 2o that this reaction might also involve a quinquecovalent intermediate analogous t o (7) with ADP in place of inorganic phosphate. (6)

+ ADP

--+

HO,CCH,COCO,H

+

ATP

Reagents: CO,, phosphoenolpyruvate carboxykinase

Scheme 4

Details of the flavin mononucleotide binding have been discerned from the crystal structure of the oxidized form of flavodoxin, a flavoprotein isolated from DesuIfouibrio vuZgaris.22The two carbonyl groups and the two N atoms of the pyrimidine ring in the isoalloxazinemoiety are hydrogen-bonded to the peptide chain while the two methyl groups are exposed on the surface of the protein. The phosphate group is inside the protein and is extensively hydrogenbonded to it. 3 Sugar Phosphates

Synthesis.--Comprehensive reviews on glycosyl esters of nucleoside pyrophosphatesz3 and teichoic acids24have appeared in the past year as have details of the preparation of xylulose-5-phosphate using transketolase.2 5 Phosphorylation of glucose by inorganic phosphate in the presence of histidine occurs under simulated primitive earth conditions and the reactive species is probably an N-phosphorylated histidine.26 Phosphorylation of sugars by heating them with 100% phosphoric acid in cacuo is a novel experimental!

ao *1

pa

J. M. Willard and I. A. Rose, Biochemistry, 1973, 12, 5241. W. E. O’Brien, R. Singleton, jun., and H. G. Wood, Biochemistry, 1973, 12, 5247. R. S. Miller and M. D. Lane, J. Biol. Chem., 1965, 243. 6041. K. Watenpaugh, L. C. Sieker, and L. H. Jensen, Proc. Nut. Acad. Sci. U.S.A., 1973,70 3857. N. K. Kochetkov and V. N. Shibaev, Adv. Carbohydrate Cliem., 1973,28, 307, J. Baddiley, Essays in Biochem., 1972, 8, 35. T. Wood, Preparative Biochem., 1973, 3, 509. W. Stillwell, G. Steinman, and R. L. McCarl, Bio-org. Chem., 1972, 2,, 1 ,

Phosphates and Phosphonates of Biochemical Interest

129

technique which has been describedrecently 28 some form of polyphosphoric acid must be the phosphorylating agent in this instance. Diphenyl phosphorochloridate has been used in the synthesis of D-glycero-L-manno-heptose dihydrogen phosphate (8), an enantiomorph of the naturally occurring L-glycero-D-manno-heptose phosphate.30 ;279

CH,OPO,H,

I

c=o

I

I

HO

1

OH

C HOPO,H, ~

Skeletal muscle and yeast phosphofructokinases will catalyse the phosphorylation of 5-keto-D-fructose-1,6-bisphosphate (9).31The latter has been isolated chromatographicallyand identified by its phosphorus content and the rather doubtful method of acid lability of the phosphate groups.32The bisphosphate is a competitive inhibitor of the reaction between aldolases and fructose-l,6-bisphosphateprobably because of Schiff base formation with the enzyme. Spectroscopic Properties.-The phosphomannan of the yeast Hansenula capsulata is too viscous for spectroscopic studies. Partial hydrolysis, however, affords a phosphate of 2-0-/3-~-mannopyranosyl-~, /3-D-mannose which has been studied. From 13C-O-31Pcouplings in the lSC n.m.r. spectrum of this phosphate and a comparison with the spectrum of the dephosphorylated This has mannobiose, the structure of the phosphate was deduced to be YH,OH

CH2OPO,H2

V. N. Shibaev, Y. Y . KUSOV, S. Kuchar, and N. K. Kochetkov, Iszvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 430 (Chem. Abs., 1973, 79, 18 963). N. K. Kochetkov, V. N. Shibaev, Y .Y . Kusov, and M. F. Troitskii, Zszuest. Akad. Nauk S.S.S.R., Ser. khim, 1973, 425 (Chem. Abs., 1973, 79, 18 964). P. Szab6, J.C.S. Perkin Z, 1974, 920. In M. W. Slein and G. W. Snell, Proc. SOC.Exp. Biol. Med., 1953, 82, 734. G. Avigad and S. Englard, Biochim. Biophys. Acta, 1974, 343, 330. L. L. Leloir and C. E. Cardini, Methods in Enzymol., 1957, 3, 840. 8 a P. A. J. Gorin, Canad. J. Chem., 1973, 51, 2105. 97

130

Organophosphorus Chemistry

led to a revision of the structure of the phosphomannan which is now thought to be more branched than originally Unlike other techniques of mass spectrometry, field desorption does not require vaporization of the sample prior to ionization. The field desorption technique has been suggested35 as a method to determine the molecular weights of sub-milligram quantities of involatile substances such as sugar phosphates without derivatization. Addition of dialkyl phosphites to 3-nitro-2,3-dideoxyhexenopyranose (1 1),3s or 1,2-dideoxyhexenopyranose(1 2) 37 gives rise to phosphonates. An alternative route to sugar phosphonates involves the addition of dialkyl phosphites to 2-keto-sugars.8 8

CH,O, CMe

CH,O,CMe

MeCO,

-

ll

0 4 Phospholipids Isoprenoid Lipids.-Lipids which contain a mono- or pyro-phosphate link between a polyisoprenoid alcohol and a carbohydrate residue are important intermediates in the biosynthesis of bacterial cell walls. The monophosphate derivatives are probably involved in the addition of single carbohydrate residues to existing polysaccharide chains while the pyrophosphates are probably intermediates in the biosynthesis of the main chain.3BFicaprenyl farnesyl (13; n = 2),40 dolichyl (14; n = 18),41 and citro(13; n = nellyl (14; n = 1) 41 a-D-mannopyranosyl phosphates have now been 84

as

so

4o 41

M. E. Slodki, Biochim. Biophys. Acta, 1963, 69, 96. H. R. Schulten, H. D. Beckey, E. M. Bessell, A. B. Foster, M. Jarman, and J. H. Westwood, J.C.S. Chem. Comm., 1973, 416. H. Paulsen and W. Greve, Chem. Ber., 1973, 106,2114. H. Paulsen and J. Thiem, Chem. Ber., 1973, 106,3850. H. Paulsen and W. Greve, Chem. Ber., 1974, 106,2124. M. Scher and W. J. Lennarz, Biochim. Biophys. Acta, 1972, 265, 417. C. D. Warren and R. W. Jeanloz, Biochemistry, 1973, 12, 5031. C.D. Warren and R. W. Jeanloz, Biochemistry, 1973, 12, 5038.

131

Phosphates and Phosphonates of Biochemicial Interest

synthesized and characterized. These phosphate esters were obtained by conphosphate with the densation of 2,3,4,6-tetra-O-acetyl-cc-~-mannopyranosyl corresponding alcohol in the presence of tri-isopropylbenzenesulphonyl chloride. Deacetylation of the resulting phosphodiesters was achieved by the action of sodium methoxide. An active intermediate of mannan biosynthesis in Micrococcus luteits and (I 3 ; n = 10) were chromatographically indistinguishable. In the case of (14) low yields of phosphodiester were obtained with the sulphonyl chloride, and DCCD was found to be more effective for this

CH3

HOCH,CH=C-CH,

4

CH3

r

F3

HOCH,CH,CH-CH,

H

CH,CH=C--CH,

i; 1

CH3

CH,CH=C-CH,

H

~ y n t h e s i sComparison .~~ of (14;n = 18) and a mannolipid from calf pancreas showed them to be identical and the synthetic material stimulated the incorporation of [14C]mannosefrom GDP-[14C]mannoseinto endogenous mannolipid in the presence of the microsomal preparation. Calf pancreas micro2-dolicholpyrosomes also produce P 1-2-acetamido-2-deoxy-~-glucosyl-P phosphate42 which has been identified by comparison with the synthetic compound.4 3 Glycosyl phosphoryl polyprenols have been identified in extracts of Mycobacterium smegmatis 44 and a dolichol pyrophosphate is thought to be involved in the biosynthesis of NN’-diacetyl-chitobiosein liver microsomes. 1nositols.-The enzyme which converts glucose-6-phosphate (1 5) into I-L-myoinositol-1-phosphate (16) removes the pro-S rather than the pro-R hydrogen atom from the C-6-position in the glucose p h o ~ p h a t e .5-Keto~~ glucose-6-phosphate (1 7) is an intermediate in this c o n ~ e r s i o n .In ~ ~the suggested mechanism 4 6 (Scheme 5 ) the loss of the p r o 4 hydrogen from (17) gives an intermediate with an s p 2 carbon atom at C-6. Cyclization of this intermediate followed by reduction then affords (1 6). Several multivalent anions, including inositol hexaphosphate (18), lower the oxygen affinity of haemoglobin. The crystal structure of the complex of

43 44 46

47

M. A. Ghalambor, C. D. Warren, and R. W. Jeanloz, Biochem. Biophys. Res. Comm., 1974, 56, 407. C. D. Warren, Y.Konami, and R. W. Jeanloz, Carbohydrate Res., 1973, 30, 257. J. Schutz and A. D. Elbein, Arch. Biochem. Biophys., 1974, 160, 311. L. F. Leloir, R. J. Staneloni, H. Carminatti, and N. H. Behrens, Biochem. Biophys. Res. Comm., 1973, 52, 1285. S. M. Byun, R. Jenness, W. P. Ridley, and S. Kirkwood, Biochem. Biophys. Res. Comm., 1973, 54, 961. J. E. G. Barnett, A. Rasheed, and D. L. Corina, Biochem. J., 1973, 131, 21.

132

Organophosphorus Chemistry

HO

L

OH

OH

OH

OH (16) Reagents: i, NAD'; 2, NADH

Scheme 5

deoxyhaemoglobin with (18) has now been published48and it shows many similarities with the ~-2,3-diphosphoglycerate-haemoglobincomplex.49In avian erythrocytes, inositol 1,3,4,5,6-~entaphosphate(19) functions as a regulator of oxygen affinity50 and it has been predicted 4 8 that (19) takes up the same position in chicken deoxyhaemoglobin as (18) does in human deoxyhaemoglobin. The 31Pn.m.r. of phospholipids and lipoproteins has been studied extensively in the past year. The phosphorus resonances of phosphatidylethanolamine, phosphatidylserine, and related phospholipids occur in the same region of the spectrumS1downfield of the resonance of phosphatidylcholine. This difference in chemical shifts is probably due to deshielding of the phosphorus by intramolecularhydrogen-bonding at the phosphoryl oxygens. In the case of phosphatidylcholine, there are no protons available on the N-atom for hydrogen-bonding with the phosphoryl oxygens and this deshielding does not occur. Highly resolved 31Pn.m.r. spectra of human serum lipoproteins that have been obtained have shown the influence of the nature of the counter cation on the polar phosphate head This technique has been used to show the presence of artefacts in old phospholipid samples. A. Arnone and M. F. Perutz, Nature, 1974, 249, 34. A. Arnone, Nature, 1972, 237, 146. b o L. F. Johnson and M. E. Tate, Canad. J. Chem., 1969,47, 63. I1 T. 0. Henderson, T. Glonek, and T. C. Myers, Biochemistry, 1974, 13, 623. b z T. Glonek, T. 0. Henderson, A. W. Kruski, and A. M. Scanu, Biochim. Biophys. Acta, 1974,348, 155; G. Assmann, E. A. Sokoloski, and H. B. Brewer, jun., Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 549.

4*

4u

Phosphates and Phosphonates of Biochemical Interest

133

5 Biochemically Active Phosphonates ArninoethyIph~sphonate.-~~Pn.m.r. measurements indicate that 78 % of the phosphorus present in a water-soluble glycoprotein from the sea anemone Metridiurn dianthus is in the phosphonate form and includes 2-aminoethylphosphonic acid (20).5331PN.m.r. for the identification of naturally occurring phosphonates appears to be a technique superior to chromatography, which has been used hitherto.54 -0

I

+

NH,CH,CH,P-=O

I

OH

(20)

CH, (CH, ),CH=CH

(CH,),CII=CHCHO

I + HCHCH,0PCH,CH,NH3

I

CH,(CH, ),,CONH

II

0

(21)

The structure of a ceramide aminoethylphosphonate from Metridiurn senile has been shown to be (21).55Hydrolysis of (21) by phospholipase gave (20) which was identified by g.1.c. and mass spectrometry. The ceramide fraction after this hydrolysis was itself hydrolysed by alkali, and the fatty acids together with the long-chain bases were also identified by g.1.c.-m.s. The composition of the long-chain bases was found to differ between anemones captured in April and in August; the former lacked sphingosine. Phosphonomycin.-Yet another synthesis of phosphonomycin (22) has appeared 56 (Scheme 6). The phosphonoaldehyde(23) was treated with pentan3-one and cyclohexylamine to give (24), which was then converted into its oxime. Tosytdtion of this oxime followed by treatment with bicarbonate caused the molecule to fragment, liberating the dimethyl ester of (22). Disodium phosphonoacetic acid when administered orally or topically to mice infected with Herpes simpkx virus will reduce significantly the mortality of mice caused by this virus.5 7 N-Phosphonomethyl-glycine58 is a promising herbicide. Recent work has shown that it exerts its effect by inhibiting the biosynthesis of aromatic amino-acids.6 9 6 Oxidative Phosphorylation As mentioned in Chapter 8, a mechanism for ATP synthesis involving a quinquecovalent intermediate has been put forward6* in a review which emphasizes that the phosphorylation mechanism is mechanistically indepen6s

54 66

56

6'

5s

R. L. Hilderbrand, T. 0. Henderson, T. Glonek, and T. C. Myers, Biochemistry, 1973, 12, 4756. D. S. Kirkpatrick and S. H. Bishop, Biochemistry, 1973, 12, 2829. K. A. Karlsson and B. E. Szmuelsson, Biochim. Biophys. Acta, 1974, 337, 204. R. A. Firestone, U.S.P. 3 784590 (Chem. Abs., 1974, 80, 60031). N. L. Shipkowitz, R. R. Bower, R. N. Appell, C. W. Nordeen, L. R. Overby, W. R. Roderick, J. B. Schleicher, and A. M. Von Esch., Appl. Microbiol., 1973, 26, 264. P. C. Crofts and G. M. I
Organophosphorus Chemistry

134

0

0

Meo\I

/

PCHO

I1

4 (MeO),P-CHOH

I

Me0

EtCHCMe

(23)

0

II

Reagents: i

,

v

, C,HllNH,; ii, NH,OH; iu, p-CH,C,H,SO,CI;

0

iv, NaHCO,; v, demethylation

Scheme 6

dent of the oxidation-reduction reactions in oxidative phosphorylation. The synthesis of ATP by mitochondria1 ATP synthetase may also involve a quinquecovalent intermediate. In a solid-state theory of oxidative phosphorylation which invokes lattice vibrations or phonons for energy transfer, it has been suggested that the phonons released during redox reactions of the electron-transport chain can be propagated by solid-state processes to the site of initial bond formatioas2Possible experimental tests for this theory have also been presented, e.g. direct excitation of the proteins by i.r.-active vibrational modes may result in the necessary lattice vibrations for phosphorylation, ion transport, etc. Since the exchange of oxygen between orthophosphate (Pi) and water in oxidative phosphorylation differs in its sensitivity to uncouplers compared with exchanges involving ATP, it has been proposeds3that the Pi-water exchange may result from a rapid reversible hydrolysis of a tightly but non-covalentIy bound ATP at the catalytic site of oxidative phosphorylation. Evidence has been presented that the energy source for motility in bacteria is an intermediate in oxidative phosphorylation and not ATP itself.s4This is in contrast to eukaryotes where ATP is utilized directly, s1

E. F. Korman and J. McLick, Bio-org. Chern., 1973, 2, 179. 1974, 44, 191. P.D. Boyer, R. L. Cross, and W. Momsen, Proc. Nat. Acad. Sci. U.S.A., 1973,70,2837. S . H. Larsen, J. Adler, J. J. Gargus, and R. W. Hogg, Proc. Nat. Acad. Sci. U.S.A., 1974, 71, 1239.

'' K. D. Straub, J. Theoret. Biol., 'a

''

Phosphates and Phosphonates of Biochemical Interest

135

e.g., in muscle contraction. Since arsenate-treated bacteria swim normally but

fail to show evidence of chemotaxis, some additional factor is required for the latter process. This factor may be ATP itself or one of its degradation products, e.g. CAMP or S-adenosylmethionine. A simple chemi-osmotic molecular mechanism for reversible proton-translocating ATPases has been put forward together with ideas for testing some of the postulates in the mechani~rn.~~

7 Enzymology Phosphoproteins.-Cleavage of ATP coupled to ion transport in microsomal preparations proceeds with the phosphorylation of an enzyme carboxy-group6 6 and it has now been established that the bridge oxygen of the enzyme acyl phosphate is derived from the carboxy-group of the enzyme.67Reduction of the acyl phosphate with sodium [3H]borol.lydrideto form a labelled aminohydroxy residue is a new method for characterizingphosphorylated proteins.6 8 This technique has been used to show that the phosphoryl group of sarcoplasmic reticulum ATPase is attached to the P-carboxy-group of an aspartyl residue at the active site. Enterobacteria aerogenes can be grown when dimethyl phosphate is the sole source of p h o s p h o r u ~ and , ~ ~ under these conditions a phosphodiesterase can be isolated from the micro-organism which utilizes dialkyl esters of phosphoric acid as substrates.70 Phosphodiesterases which have been isolated hitherto utilize nucleoside 2',3'- or 3',5'-phosphates and 4-nitrophenyl esters as substrates. A study 71 has confirmed the hypothesis 7 2 that phosphate binds to uridine phosphorylase before uridine, and that uracil leaves the enzyme before ribose-1-phosphate. Active Site Labelling.-Treatment of ethanolamine phosphate with bromoacetyl bromide affords (25), which is an active-site reagent for aldolases even though it is not a particularly close structural analogue of aldolase substrate~.~" Alkylation of aldolases by (25) does not result in total inactivation of the enzyme as the reagent is not specific for a single amino-acid residue. The inactivation does, howevei, take place primarily by alkylation of a histidine residue, which has been identified as the one adjacent to the penultimate residue.7 4 Phosphoglycollohydroxamic acid (26) is a close structural analogue of dihydroxyacetone phosphate (27) but is unlikely to form a Schiff base with lysine residues owing to electron delocalization over the carbonyl group. 65

P. Mitchell, F.E.B.S. Letters, 1974, 43, 189.

'' T. Kanazawa, S. Yamada, T. Yamomoto, and Y. Tonomura, J. Biochem. (Japan), 197 1 b7

'O

'I1

'I8

'Iq

70, 95; A. N. Neufeld and H. M. Levy, J. Biol. Chem., 1970,245,4692. A. S. Dahms, T. Kanazawa, and P. D. Boyer, J. Biol. Chem., 1973, 248, 6592. C . Degani and P. D. Boyer, J . Biol. Chem., 1973, 248, 8222. R. Wolfenden and G. Spence, Biochim. Biophys. Acta, 1967, 146, 296. J. A. Gerlt and F. H. Westheimer, J . Amer. Chem. SOC.,1973, 95, 8166. R. Bose and E. W. Yamada, Biochemistry, 1974, 13, 2051. A. Kraut and E. W. Yamada, J . Biol. Chem., 1971, 246, 2021. F. C. Hartman, B. Suh, M. H. Welch, and R. Barker, J. Biol. Chem., 1973, 248, 8233. F. C. Hartman and M. H. Welch, Biochem. Biophys. Res. Comm., 1974, 57, 85.

136

Organophosphorus Chemistry

However, (26) should bind strongly to class I1 aldolases on account of its chelating ability and this has been found to be the case with rabbit muscle fructosediphosphate aldolase where (26) functionsas a competitive inhibitor.76 Triose phosphate isomerase is also strongly inhibited by (26);7617 6 this may be due to its similarity to the cis-enediolate (28), which is an intermediate in the reaction pathway of this enzyme.7 7 Acyldihydroxyacetone phosphates are important intermediates in the biosynthesis of glycerolipids7 8 and the acyl HONHCOCH,OPO,H, BrCH,CONHCH,CH, OPO, & (25 1

(26) HOCH=CCH,OPO,H,

I

HOCH, COCH, OPO&

-0 (281

(27)

H+ 0

II I -0

+ RCOOPOCH,COCH,OH

(30)

group can be transferred enzymically in mitochondria to various phospholipid receptor~.~@ This ready transfer of the acyl group may be due to the intermolecular formation (29) of an acyl phosphate (30), which then reacts with lipid substrates. 3-Bromo-2-butanone-l,4-bisphosphonate has been prepared and used as an affinity label for ribulose biphosphate carboxylase.80 Cho1inesterases.-The inactivation of acetylcholinesterase by phosphorofluoridates is well knowns1 and it has recently been shown that phosphorochloridates and 0-isopropyl-S-(di-isopropylaminoethyl)methylthiophosphonate (31) 83 are inactivators of this enzyme. Phosphorochloridates are hydrolysed much more rapidly than the corresponding phosphorofluoridates and have a rather higher activity as cholinesterase inactivators.82The effect of 7s

7p 78

8a

D. J. Lewis and G. Lowe, J.C.S. Chem. Comm., 1973, 713. K. D. Collins, J. Biol. Chem., 1974, 249, 136. S. V. Rieder and I. A. Rose, J. Biol. Chem., 1959, 234, 1007. A. K. Hajra, Biochem. Biophys. Res. Comm., 1968, 39, 1037. A. K. Hajra, Biochem. Biophys. Res. Comm., 1974, 57, 668. F. C. Hartman, M. H. Welch, and I. L. Norton, Proc. Nat. Acad. Sci. U.S.A., 1973,70, 3721. B. C. Saunders, ‘Some Aspects of the Chemistry and Toxic Action of Organic Compounds containing Phosphorous and Fluorine’, Cambridge University Press, Cambridge, 1957. P. Wins and I. B. Wilson, Bioclzim. Biophys. Acta, 1974, 334, 137. J. Patocka and J. Bajgar, Coll. Czech. Chem. Comm., 1973, 38, 3940.

Phosphates and Phosphonates of BiochemicalInterest

137

various parameters on the ageing of phosphorylated cholinesterases has been studied.a4

The chemical shift of the phosphorus resonance of various nucleotides has been studied as a function of pH in the presence and absence of RNase A.85 The 31Psignal shifts upfield on protonation of the phosphate and the apparent PKa of the phosphate group in 2’-CMp complex with RNase is the same as the PKa of histidine-119 in this enzyme as determined by lH n.m.r.88From 31P n.m.r. relaxation rates for the ternary complex manganese@)-phosphateE. coli alkaline phosphatase, it has been concluded that an outer-sphere complex is formed which has a shorter lifetimethan the enzyme turnover rate.87 The latter conclusion is consistent with the participation of the complex in the enzymic reaction. 8 Other Compounds of Biochemical Interest

Presqualene pyrophosphate (32), a compound whose structure has caused considerable controversy in the past, has been isolated from intact rat liver and a yeast microsomal system.aa Previously, (32) had been detected only in systems which have been starved of NADH and hence the new findings demonstrate that (32) is not an artefact. Despite earlier evidencea9 that lycopersene is a precursor of phytoene, a recent stereochemical analysis of phytoene synthesisg0makes this appear to be unlikely, and a mechanism has been proposed for the synthesis of cis- and trans-phytoene directly from prephytoene pyrophosphate (33) (Scheme 7). This mechanism is similar to one proposed for squalene s y n t h e ~ i s . ~ ~ Among new polyphosphate esters which have been isolated recently are retinol pyrophosphate from rat thyroid 92 and trans-farnesyl triphosphate from Gibberellafujikuroi. B3 In each case the terminal phosphoryl residue in ATP was incorporated into the polyphosphate, but in neither case has a biological J. H. Keijzer, G. Z. Wolring, and L. P. A. de Jong, Biochim. Biophys. Acta, 1974, 334, 146. W. Haar, J. C. Thompson, W. Maurer, and H. Ruterjans, European J. Biochem., 1973, 40, 259. B6 D. H. Meadows, 0. Jardetzky, R. M. Epaud, H. H. Ruterjans, and H. A. Sheraga, Proc. Nut. Acad. Sci. U.S.A., 1968, 60,766. R. S. Zukin, D. P. Hollis, and G . A. Gray, Biochem. Biophys. Res. Comm., 1973,53,238. F. Muscio, J. P. Carlson, L. Kuehl, and H. C . Rilling, J. Biol. Chem., 1974, 249, 3746. F. J. Barnes, A. A. Qureshi, E. J. Semmler, and J. W. Porter, J . Biol. Chem., 1973, 248, 2768. e o D. E. Gregonis and H. C. Rilling, Biochemistry, 1974, 13, 1538. C. D. Poulter, 0. J. Muscio, and R. J. Goodfellow, Biochemistry, 1974, 13, 1530. K. Gaede and P. Rodriguez, Biochem. Biophys. Res. Comm., 1973, 54, 76. I. Shechter, Biochim. Biophys. Acta, 1973, 316, 222.

84

Organophosphorus Chemistry

138

‘H

HR

‘R

-Y

Y MeH M $e /

R cis-phytoene

R trans-phytoene

Scheme 7

function been found. Mono- and pyro-phosphate esters of phytanol and phytol have been prepared by the phosphorochloridate method and their degradation studied in aqueous methanolic acid.04The degradation products of the labile phytyl phosphateswere consistent with the formation of carbonium ion intermediates. The saturated phytanol pyrophosphate was hydrolysed rapidly to the phosphate which was comparatively stable. The reaction of a number of monoterpenes with diethyl hydrogen phosphite affords phosphonates which have flame retardant properties. 95 A total synthesis of the insecticidal exotoxin (34;R1 = R2 = R3 = H, R4 = POSH2)was achieved Q6 by the action of phosphorus oxychloride on the protectednucleoside(34;Rl = PhC0,R2 = MeC0,R3 = Me,R4 = H); hydrolysis of the initial phosphorylation product with sodium hydroxide gave u4

96

96

C . N. Joo, C. E. Park, J. K. G . Kramer, and M. Kates, Canad. J. Biochem., 1973, 51, 1527. R. L. Kenney and G. S. Fisher, J . Org. Chem., 1974, 39, 682. L. Kalvoda, M. Prystgs, and F. Sorm, Tetrahedron Letters, 1973, 4671.

139

Phosphates and Phosphonates of Biochemical Interest

the exotoxin. It is remarkable that no intramolecular migration of the phosphate was observed during the alkaline hydrolysis. COOR3

NHR’

I

I

R&H

I I R’WH I C RWH

0

I

A blue fluorescent compound isolated from Photobacterium phosphoreiim has been identified as ~-evythro-neopterin-2’,3’-cyclicphosphate (35) by degradation and comparison with the synthetic cyclic ph~sphate.~’ The latter was obtained by treatment of the 3’-phosphate with DCCD.97 0

Np/OH

’ 0 0 ‘

I

-CH-CH,

I

Cyclophosphamide (36; R = H) is an effective agent for the treatment of many animal and human tumours 9 8 and is oxidized in vivo by a mixed function oxidase of liver microsomes to produce a cytotoxic form of the drug.99It was reported earlier loo that 4-hydroxy-cyclophosphamide (36; R = OH), a product of the oxidation of (36; R = €1) with Fenton‘s reagent, was the

A. Suzuki and M. Goto, Biochim. Biophys. Acta, 1973, 304, 222. K . Sugiura, H. Yamashita, and M. Goto, Brill. Cliem. Soc. Japan, 1972, 45, 3564. D. L. Hill, W. R. Laster, jun., and R. F. Struck, Cancer Res., 1972, 32, 658. l o o A. Takamizawa, S. Matsumoto, T. Iwata, K. Katagiri, Y. Tochino, and K. Yamaguchi, J. Amer. Chem. Sac., 1973, 95, 985.

140

Organophosphorus Chemistry

active cytotoxic agent but this has now been challenged.l0lPlo2 The product of the oxidation of (36; R = H) with ferrous sulphate and hydrogen peroxide is the dimer (37). This is an active anti-tumour agent.

lol lo8

A. Takamizawa, S. Matsumoto, and T.Iwata, Tetrahedron Letters, 1974, 517. R. F. Struck, M. C. Thorpe, W. C. Coburn, jun., and W. R. Laster, jun., J . Amer. Chem. SOC.,1974,96, 313.

8 Nucleotides and Nucleic Acids BY J.

B. HOBBS

1 Introduction The papers published during the past year in the field of nucleotide and polynucleotide chemistry have been less remarkable for innovative chemistry than for biochemical application, and sheer volume has necessitated much pruning of the material available. The appearance of a new journal - NucZeic Acid Research - is symptomatic of the increasing publication in this area. Cyclic AMP research, Sutherland’s monument, has yielded many new compounds, and no attempt has been made to cover the huge quantity of biochemical and pharmacological data available on these, for which the reader is advised to seek specificreviews. Affinity labelling and affinity chromatography continue to justify the wide research effort they command. 2 Mononucleotides Chemical Synthesis.-Two new methods for 5’-phosphorylation of nucleosides have been described. In the first,l phosphorous acid and mercuric chloride are heated at 80 “C in N-methylimidazole,and a 2’,3’-O-isopropylidene-protected nucleoside is added. On work-up the 5’-phosphate is obtained in -70% yield. The phosphorylating agent is presumed to be an N-phosphory1-N’methylimidazolium species (1). The second method employs tris-(8-quinolyl)

’

-0

-\

phosphate (2),prepared from 8-hydroxyquinolineand phosphorus oxychloride. Heating unprotected nucleosides with (2) in pyridine affords bis-(8-quinolyl)nucleoside5’-phosphates,from which the quinolyl groups can be removed with cupric ion to give the nucleotide in 40-60 % yield. The use of phosphorus oxychloride in trimethyl phosphate continues to be a popular procedure for H. Takaku, Y.Shimada, and H. Oka, Chem. and Pharm. Bull. (Japan), 1973,21, 1844. H. Takaku and Y . Shimada, Tetrahedron Letters, 1974, 1279.

141

Organophosphorus Chemistry

142

phosphorylating protected or unprotected nucle~sides.~-~ However, the method is not universally applicable; using xylonucleosides, the 3’,5’-cyclic phosphate is obtained and when 1-(2,3-dihydroxypropyl)thymine (3) is treated with this reagent, the 3’-phosphate is formed.8However, if unprotected

I

CH(0H)

NH, (3)

(4 1

9-a-0-mannofuranosyladenine (4) is so treated, the 5’-phosphate is formed as sole p r o d ~ c tSimilar .~ treatment of the 2’,3’-@isopropylidene derivative of (4) gives a mixture of 5’- and 6’-phosphates. Thus the one case shows preferential phosphorylation at the secondary hydroxy-group, the other at the primary. Specific protection of a hydroxy-group by intramolecular hydrogen-bonding may be the decisive factor in these reactions. Phosphorus oxychloride has also been used for direct phosphorylation of 2’-deoxy- lo and other 2’-substituted nucleosides,6for cyclonucleosidescontaining sulphur l1and oxygen l2 bridges l3 5’-Protected to the 2’-position, and for 3’-amino-3’-deoxyadenosine. deoxynucleosides may be phosphorylated directly at the 3’-hydroxy-group using equimolar quantities of phosphorus oxychloride and pyridine in dioxan at room temperature, and protecting groups which are iiormally acid-sensitive stay intact.14 Phosphoramidates may be phosphorylated thus. The intermediate phosphodichloridate formed may be used for further coupling to give a dinucleoside phosphate, if required. The 6’-phosphonate analogue of ribavirin (5 ; l-~-~-ribofuranosyl-1,2,4triazole-3-carboxamide) has been synthesized by oxidizing the 5’-hydroxyA. Hanipton, P. Howgate, P. J. Harper, F. Perini, F. Kappler, and R. K. Preston, Biochemistry, 1973, 12, 3328; C. I. Hong and G. B. Chheda, J . Medicin. Chem., 1973, 16, 956. ’ M. Ikehara, T. Fukui, T. Koide, and J. Inaba, Nucleic Acid Res., 1974, 1, 53. M. Hattori, M. Ikehara, and H. T. Miles, Biochemistry, 1974, 13, 2754. J. Hobbs, H. Sternbach, M. Sprinzl, and F. Eckstein, Biochemistry, 1973, 12, 5138. ’I A. Holy and I. Votruba, CON.Czech. Chem. Comm., 1974, 39, 1646. A. Holy and G. S. Ivanova, Nucleic Acid Res., 1974, 1, 19. * M. J. Taylor, B. D. Kohn, W. G. Taylor, and P. Kohn, Carbohydrate Res., 1973,30, 133. A. Holy, Coll. Czech. Chem. Comm., 1973, 38, 3912. l 1 K . K. Ogilvie and L. A. Slotin, Canad. J. Chem., 1973, 51, 2397. l a M. Ikehara and T. Tezuka, Nucleic Acid Res., 1974, 1, 479. l a M. Morr and M.-R. Kula, Tetrahedron Letters, 1974, 23. l 4 W. S. Mungall, G. L. Greene, P. S. Miller, and R. L. Letsinger, Nucleic Acid Res., 1974, 1, 615. @

143

Nucleotides and Nucleic Acids H,NOC

methyl group of 2’,3’-O-isopropylideneribavirinwith DCCD and DMSO and condensing the resulting aldehyde with a Wittig reagent.16The phosphonate is an inhibitor of IMP dehydrogenase from Escherichiu coli. 6’-Cyano-6’deoxyhomoadenosine-6’-phosphonic acid (6) has been prepared l 6 by condensing protected 5’-deoxy-5’-iodoadenosinewith the sodium salt of diethyl cyanomethylphosphonate. The corresponding ADP and ATP analogues were also prepared. The acid (6)is a substrate for rabbit and pig AMP kinases, but

0

I[

HO-P-CH(CN)

OH HO OH (6)

only one 6’-epimer is a phosphoryl acceptor, and for the reverse reaction only one epimer of the ATP analogue was a phosphoryl donor. Donor and acceptor had opposite configurations. When 5’-O-tritylthymidine-3’-phosphate is treated with excess tri-isopropyl benzenesulphonylchloride (TPS) and thymidine, and then deprotected, the trinucleoside monophosphate (7a) is obtained.l 7The 5-bromo- and 5-flUOrOdeoxyuridine analogues (7b) and (7c) are prepared similarly. All are resistant to snake venom and spleen phosphodiesterases, and hydrolyse too slowly under physiological conditions for the cytotoxic moiety to be effective.When protected UpU is treated with bis-(4-nitrophenyl) phosphorochloridate, and subsequently with an amine or amino-acid ester, the dinucleoside phosphoramidates (8) are formed.l* Although the compounds investigated split the P-N bond under the conditions required for protecting-group removal, the method has potential for the preparation of easily fissionableneutral phosphotriesters.

lo

l8

M. Fuertes, J. T. Witkowski, D. G . Streeter, and R. K. Robins, J . Medicin. Cliem., 1974, 17, 642. A. Hampton, T. Sasaki, and B. Paul, J. Amer. CIiem. SOC., 1973, 95, 4404. E. J. Norman and J. Nagyvary, J. Medicin. Chent., 1974, 17, 473. €3. A. Juodka and J . Smrt, Coil. Czech. Chem. Comm., 1974, 39, 963.

144

Organophosphorus Chemistry

ve 0

HN

ANY

0

9

,,Lx 0 OR’ R4NH-P=0

I

0

’

I

- - *-

II

I O % ”

‘ 0 ’

X = Me b; X = Br

(7)a;

c;X=F

1 1

0 0

= dimethoxytrityl etrahydropyranyl Ahoxymethylidene = C,H, or EtO,CCH,

Cyclic Nuc1eotides.-Many new analogues of cyclic 3’,5’-AMP (CAMP)have 2o some in which the sugar been prepared, some in which the base is modified,lS~ ring is modified at the 2’- 21 and 5’- 2 2 s 28 positions, and others in which the phosphate ring is altered to give a cyclic phosphonate 23 (of 1,N6-ethenoadenosine), cyclic phosphoramidates in which the nitrogen atom is located at the 3’- 84 or 5’- 2s position, or a cyclic thiophosphate in which the sulphur atom is located at the 5’-positi0n.~~ Some neutral esters of CAMP, which should have enhanced lipid solubility, have also been A systematic study of the effects of CAMP analogues in stimulating CAMP-dependent protein kinase suggests that the catalytic effect is dependent on the steric and electronic requirements of the cyclophosphate ring, with alterations elsewhere in the molecule largely affecting binding parameters. 2 8 3’,5’-Cyclic nucleotide phosphodiesterasesshow similar requirements for binding and reactivity. The ability of cell-bound CAMP-phosphodiesterasefrom Dictyostelium discoideum to bind 2os

K. H. Boswell, J. P. Miller, D. A. Shuman, R. W. Sidwell, L. N. Simon, and R. K. Robins, J. Medicin. Chem., 1973, 16, 1075; R. B. Meyer, jun., D. A. Shuman, R. K. Robins, J. P. Miller, and L. N. Simon, ibid., p. 1319; S.-Y. Chu, ibid., 1974, 17, 406; J. P. Miller, K. H.Boswell, K. Muneyama, R. L. Tolman, M. B. Scholten, R. K. Robins, L. N. Simon, and D. A. Shuman, Biochem. Biophys. Res. Comm., 1973, 55, 843. ‘O B. Jastorff and W. Freist, Bio-organic Chem., 1974, 3, 103. I1 A. M. Mian, R. Harris, R. W. Sidwell, R. K. Robins, and T. A. Khwaja, J. Medicin. Chem., 1974,17, 259. aa R. S . Ranganathan, G. H. Jones, and J. G. Moffatt, J. Org. Chem., 1974, 39, 290. G. H. Jones, D. V. IS. Murthy, D. Tegg, R. Golling, and J. G. Moffatt, Biochem. Biophys. Res. Comm., 1973, 53, 1338. ’’ M. Morr, M.-R. Kula, G. Roesler, and B. Jastorff, Angew. Chem., 1974, 86, 308. * I A. Murayama, B. JastorR, H. Hettler, and F. Cramer, Chem. Ber., 1973, 106, 3127. a* D. A. Shuman, J. P. Miller, M. B. Sholton, L. N. Simon, and R. K. Robins, Biochemistry, 1973, 12, 2781. t 7 J. Nagyvary, R. N. Gohil, C. R. Kirchner, and J. D. Stevens, Biochem. Biophys. Res. Comm., 1973, 55, 1072. B. Jastorff and H.-P. Blr, European J. Biochem., 1973,37,497. la

145

Nucleotides and Nucleic Acids

CAMP analogues correlates closely with their ability to trigger chemotactic response in amoebae.29Suspicion that cGMP is a cellular regulatory agent whose concentration is correlated, and may vary inversely, with that of cAMP30 has spurred interest, and a number of derivatives of cGMP, cIMP, and cXMP have been reported.26s31 cGMP itself is formed on heating GTP at neutral pH, a reaction catalysed by bivalent metal ions and creatine phosphate. 32 A new method for forming 2’,3’-cyclic phosphates of ribonucleosides using very mild conditions has been described.33It may also be used to introduce a terminal cyclic phosphate in protected oligonucleotides. When 2’,3’-cyclic AMP is evaporated from solution at alkaline pH in the presence of aliphatic diamines, and maintained dry at elevated temperatures, polymerization occurs. Oligomers up to the hexanucleotide are formedY3* preferentially with 3’+5’ internucleotidic links. This may have been an important process in prebiotic synthesis. Several reports have appeared concerning phosphates of cyclonucleosides in which the base is cyclized to the sugar ring. Phosphornonoesters and dinucleoside monophosphates containing 8,2’-thioanhydro-adenosine (9),

HO (9) R’ = NH,, R2 = H (10) R’ = OH, R2 = NH2 (11) R’ = OH, R2 = H

HO (12)

Hi) OH

D. Malchow, J. Fuchila, and B. Jastorff, F.E.B.S. Letters, 1973, 34, 5. G. B. Kolata, Science, 1973, 182, 149. I1 J. P. Miller, K. H. Boswell, K. Muneyama, L. N. Simon, R. K. Robins, and D. A. Shuman, Biochemistry, 1973, 12, 5310. H. Kimura and F. Murad, J . Biol. Chem., 1974, 249, 329. I*J. H. van Boom, J. F. M.deRooy, and C. B. Reese, J.C.S. Perkin I, 1973,2513. M. S. Verlander, R. Lohrmann, and L. E. Orgel, J. Mol. Evol., 1973, 2, 303. ao

Organophosphorus Chemistry

146

-guanosine (lo), and -inosine (11),l1 02,2’-cyclouridine (i2),35 and OS,2’anhydro-6-oxy-ara-uridine(13)12 have been described, and an ApUpG analogue containing 8,5’-O-cycloadenosine(14) has been synthesized 36 using standard methods. Because of their fixed conformation, these compounds provide interesting information on the substrate specificity of hydrolytic enzymes. The 5’-phosphates of (9), (lo), (ll), and (13) are not hydrolysed by snake venom 5’-nucleotidase. The dinucleoside (3’+ 5’) monophosphates of (12) and (13) are not degraded by spleen phosphodiesterase,1z+35 and are hydrolysed slowly,12 or not at all,36 by snake venom phosphodiesterase. Dinucleoside monophosphates in which (1 2) forms the 5’-end are degraded by snake venom phosphodiesterase, but not spleen, and zke versa when (1 2) is at the 3’-end.12 Affinity Chromatography.-If 6-mercaptopurine riboside-5’-phosphate (1 5 ) is heated with a large excess of aqueous 1,6-diaminohexane,NG-(6-aminohexy1)5’-AMP is formed. This couples quantitatively to cyanogen-bromide-activated Sepharose, forming an affinity column for several dehydrogenases and kina~es.~’ This system has been studied extensively with respect to the nature of the support, influence of concentration of enzyme and ligand,38length and nature of spacer arm,39and other parameters. These insoluble AMP derivatives have been used to separate the isozymes of lactate dehydrogenase40and SR

tz = I , R = 11 (16) n = 3, R = 2,4-dinitrophenyl

(15)

to immobilize glycogen phosphorylase b.lf AMP is an effector for this enzyme, which thus becomes immobilized in its active conformation. A general method for preparing immobilized analogues of AMP, ATP, NAD+, etc. consists of treating the 6-mercaptopurine nucleotide with bromoacetamidohexyl Sepharose, subsequently quenching unreacted groups with mercaptoethan01.l~An alternative method for the same ATP analogue uses a spacer 35

36 37

B8

as 40

4z

K. K. Ogilvie and D . J. Iwacha, Canad. J . Chem., 1974, 52, 1787. M. Ikehara, T. Nagura, and E. Ohtsuka, Chem. andPharm. Birll. (Japan), 1974,22, 123. D. B. Craven, M. J. Harvey, C. R. Lowe, and P. D. G . Dean, European f. Biocheni., 1974, 41, 329 and following papers. C. R. Lowe, M. J. Harvey, D. B. Craven, and P. D. G. Dean, Bioclrem. J., 1973,133,499. M. C. Hipwell, M. J. Harvey, and P. D . G. Dean, F.E.B.S. Letters, 1974, 42, 3 5 5 . P. Brodelius and K. Mosbach, F.E.B.S. Letters, 1973, 35, 223. K. Mosbach and S. Gestrelius, F.E.R.S. Letters, 1974, 42, 200. S. Barry and P. O’Carra, F.E.B.S. Letters, 1973, 37, 134.

Nucleotides and Nucleic Acids

147

arm terminating in a sulphydryl group, which is used to displace 2,4-dinitrothiophenolate from 6-(2,4-dinitrothiophenyl)purine riboside-5’-triphosphate (16).43This has been used successfullyfor Na+, K+-ATPasefrom bovine brain. By studying the binding of staphylococcal nuclease to thymidine-5’-phosphate3’-aminophenylphosphateSepharose, methods have been defined for determining binding constants for the affinity matrix, or for soluble Iigand~.*~ A broad review on affinity chromatography, covering methods for attaching nucleotides and polynucleotides, has appeared.46 The photoaffinity label O2-(ethyl-2-diazomalonyl)adenosine-3’,5’-cyclic phosphate (17) has been used to label rabbit muscle phosphofructokinase.If

the a 5 i t y label is constantly renewed by a dialysis system during the labelling experiment, some 70-75 % of the binding sites can be labelled.46Compound (17) has also been used to label the CAMPreceptor in intact human erythrocyte Only the regulatory subunit of endogenous CAMP-dependent protein kinase is thought to be labelled. When 3H-labelIed CAMP itself is incubated with tissue extracts for which it shows high affinity, and then irradiated, the tissue becomes labelled.4 8 Incorporation is inhibited by cold CAMP, and competing analogues, and it thus seems that cAMP may be used directly for photoaffinity labelling. 3 Nucleoside Polyphosphates Chemical Synthesis.-The phosphorimidazolidate method for the preparation of nucleoside di- and tri-phosphates has been re-examined and extended.4 9 For instance, ATP may be prepared either by activating ADP with carbonyl di-imidazole and treating the resulting phosphorimidazolidate with inorganic B. H. Anderton, F. W. Hulla, H. Fasold, and H. A. White, F.E.B.S. Letters, 1973, 37, 338. 44 B. M. Dunn and I. M. Chaiken, Proc. Nat. Acad. Sci. U.S.A., 1974, 71,2382. 411 H.Guilford, Chem. SOC. Rev., 1973, 2,249. 4 8 D.J. Brunswick and B. S. Cooperman, Biochemistry, 1973, 12, 4079. *’ C. E. Guthrow, H. Rasmussen, D. J. Brunswick, and B. S. Cooperman, Proc. Nat. Acad. Sci. U.S.A., 1973, 70, 3344. 4 8 R. S. Antonoff and J. J. Ferguson, jun., J. Biol. Chem., 1974, 249, 3319. J. W. Kozarich, A. C. Chinault, and S. M. Hecht, Biochemistry, 1973, 12,4458. 6

148

Organophosphorus Chemistry

phosphate, or by activating inorganic phosphate with the same reagent and adding ADP. The synthesis of ‘pseudo-ATP’ (18; adenosine 5’-~1,&16/triphosphate) by treating adenosine 5’-phosphordi-imidazo1idate with inorganic phosphate has been The material gives the required analysis, and behaves chromatographically and electrophoretically as expected. It shows no substrate properties for hexokinase, and is ineffectivein promoting tRNA aminoacylation. No 31Pn.m.r. data were given, however, to confirm the structure. Enzymatic Synthesis.-The phosphorimidazolidate method may be used to. prepare [y-32P]ATP.soHowever, an enzymatic method which permits synthesis of [Y-~~P]ATP with specific activity as high as 1 Ci pmol-l seems likely to be preferreds1 (Scheme 1). The system involved has been used for a number of yearssa but has been improved by adding oxidizing dyes - thiazolyl blue or phenazine methosulphate - to oxidize the NADH produced in the first step of

n

H, 3 2 PO,

CH,0P0,2-

NAD’

4

CH,0POJ2-

CH,OPO,*ADP

[T-~~P]ATP

NADH + H+

dyes

Scheme 1

61

S. M. Hecht and J. W. Kozarich, Biochim. Biophys. Acta, 1973, 331, 307. P. F. Schendel and R. D. Wells, J. Biol. Chem., 1973, 248, 8319. I. M. Glynn and J. B. Chappell, Biochem. J., 1964, 90, 147.

Nucleotides and Nucleic Acids

149

the reaction (the dehydrogenation of glyceraldehyde-3-phosphate)and render it irreversible. The ADP cofactor for the second, 3-phosphoglycerate kinasecatalysed step is thus phosphorylated to give [y-32P]ATPof the same activity as the Hs32P04supplied to the mixture. When E. coli cells in log phase are subjected to simultaneous osmotic and temperature shock, they can be rendered permeable. If ribonucleoside triphosphates are incubated with Hs32P04and shocked cells, the label is introduced as the P-ph~sphate.~~ With ATP the y-phosphate also becomes labelled. The mechanism is thought to involve polynucleotide phosphorylase, and although the levels of labelling are not very high, the procedure may be synthetically useful. The mechanism of ATP synthesis in oxidative phosphorylation has been argued in terms of a pseudorotation model,s4which allows two entry points for water oxygen. In the critical step, two oxonium functions, linked to ‘proton transfer groups’ are situated apically in a five co-ordinate intermediate. Allegedly the enzyme active site simultaneously undergoes a conformational and protonation-state change, and only the conformation attained after ATP hydrolysis can independentlycatalyse the H3P04-H20oxygen isotope exchange observed concomitantly. Thiophosphates and Phosph0ramidates.-Adenosine 5’-0-(1-thiodiphosphate) (19a) and adenosine 5’-0-(2-thiodiphosphate)(19b) are not phosphorylated by ATP synthetase in oxidative phosphorylation, but are potent inhibitors of NH,

I

X

-0-p-

I1 I -0 HO OH (19)a; X = 0, Y = S b;X=S, Y = O

HO OH (20)a; x = 0, Y = s b;X=S, Y = O *a s4

H. A. Rauk and M.Cashel, Analyt. Biochem., 1973,56, 129. J. H. Young, E. F. Korman, and J. McLick, Bio-organic Chem., 1974, 3, 1.

150

Organophosphorus Chemistry

mitochondria1 state-3 r e ~ p i r a t i o nUnlike . ~ ~ (19a), (19b) is not a substrate for nucleoside diphosphate kinase. Adenosine 5’-0-(1-thiotriphosphate) (20a) can replace ATP as substrate in hexokinase-catalysed glucose phosphorylation, but adenosine 5’-0-(3-thiotriphosphate)(20b) is inactive. Compounds (19a) and (19b) are substrates for ribonucleotide reductase from E. coli, but the rate of reduction is markedly lessened compared with ADP, particularly for (19a).66Compound (20b) is a substrate whereas (20a) is a strong competitive inhibitor 6 7 for adenylate cyclase from Ehrlich ascites cells. The stereoisomers of (20a) are equally potent, suggesting that there are no stringent structural requirements at the triphosphate group regarding binding. In the presence of phosphorylase kinase and Mg2+, (20b) phosphorylates rabbit muscle phosphorylase b to a thiophosphate analogue of phosphorylase a, which is resistant to phosphorylase phosphatase and behaves as a competitive inhibitor.s8 Protein kinase can also use (20b) to activate phosphorylase kinase (cf. hexokinase, above) and is hydrolysed rapidly by sarcoplasmic reticulum ATPase. Adenylyl imidodiphosphate (21) is a strong competitive inhibitor for mitochondrial A T P ~ SG-Actin ~ . ~ ~ binds one molecule of (21) and one bivalent

HO

bH

cation, and polymerizes to F-actin without dephosphorylating (21).60 The energy released during the ATP hydrolysis which occurs when F-actin ATP polymerizes to G-actin is thus not used for the polymerization process. 2-Methylthio- and 2-chloro-ATP and 2-chloroadenylylmethylenediphosphonate have been synthesized and tested for their ability to relax mammalian gut.61 All are more active than ATP. When ATP and 2,4,6-trinitrobenzenesulphonicacid are mixed at pH 9.5, 2’- (or 3’-) 0-(2,4,6-trinitrophenyl)adenosine-5’-triphosphate(22) is formed,6* which binds to, and is hydrolysed by, heavy meromyosin. This ATP derivative exhibits reversible formation of a Meisenheimer complex, with pK 5.1. The 66

E. Schlimme, W. Lamprecht, F. Eckstein, and R. S. Goody, European J. Biochem., 1973, 40, 485.

U. von Dobeln and F. Eckstein, European J . Biochem., 1974, 43, 215. H.-P. Bar, L. P. Simonson, and F. Eckstein, F.E.B.S. Letters, 1974, 41, 199. b8 D. Gratecos and E. H. Fischer, Biochem. Biophys. Res. Comm., 1974, 58,960. b e H. S. Penefsky, J. Biol. Chem., 1974, 249, 3579. * O R. Cooke and L. Murdoch, Biochemistry, 1973, 12, 3921. *l G. R. Gough, M. H. Maguire, and D. G. Satchel], J. Medicin. Chem., 1973, 16, 1188. I’ T. Hiratsuka and K. Uchida, Biochim. Biophys. Acta, 1973, 320, 635. 66

b7

151

Nucleotides and Nucleic Acids 0

0

il 0-P-0-P-0 I I -0 -0

II HO-P--

0

II

I

-0

wAd

0 0

I

NO2

(22) Ad = adenine

resulting marked spectral change allows the trinitrophenyl residue to act as a ‘reporter’group, giving information on the microenvironment at enzyme active sites. The reaction of 5’-amino-S-deoxyadenosinewith trimetaphosphate affords the 5’-N-triphosphate (23). When (23) is employed as substrate with glucose in the hexokinase-catalysedreaction, the 5’-N-diphosphate(24) is obtained;63the latter is cleaved by snake venom phosphodiesteraseto the 5’-phosphoramidate, and hydrolyses in acid to the amino-nucleoside. It does not appear to be polymerized by polynucleotide phosphorylase. In this context it is noteworthy that uridine 5’-S-thiopyrophosphate (25) is a competitive inhibitor for polynucleotide phosphorylase from E. coli, but not a substrate, and that the 5’4thiotriphosphates (26) and (27) show neither substrate nor inhibitory properties for RNA polymerase or DNA polymerase I, re~pectively.~~ However, (23) can be polymerized using the latter enzymeYg6 showing that the introduction of a 5’-heteroatom does not completely exclude these modified nucleotides as substrates for the polymerizing enzymes. ga

g6

J. S . Wilkes, B. Hapke, and R. L. Letsinger, Biochem. Biophys. Res. Comm., 1973, 53, 917. A. Stiitz and K.-H. Scheit, 2.physiol. Chem., 1973, 354, 1248. R. L. Letsinger, J. S. Wilkes, and L. B. Dumas, J . Amer. Chem. SOC.,1972, 94, 292.

152

Organophosphorus Chemistry

(23) n = 2 (24) n = 1 Ad = Adenine

(25) n = 1, (26) n = 2, (27) n = 2,

X X X

=

OH, Y = H Y = H Y = Me

= OH, = H,

Metal Complexes.-Metal-ion complexes of nucleotides continue to arouse interest. Chromium(m) exchanges oxygen ligands rather slowly, and a series of complexes with nucleotides has been prepared.66These are stable in acid, hydrolysing above pH 7. The complex with ATP exhibits a single negative charge, pK 2.2, suggesting that all three phosphates co-ordinate to the metal ion. These complexes inhibit a wide variety of kina~es,~' binding to the enzymes as well as, or better than, the magnesium complexes, and appear useful probes for the geometry of nucleotide binding sites. A cobalt(m)-ATP complex containing o-phenanthroline has been used as an affinity label for myosin from rabbit muscle.it Other Po1yphosphates.-The hydrolysis of the fluorescent 1,N 6-ethenoadenosine triphosphate (28) by myosin, and the fluorescence change observed on binding to heavy rneromyosin, have been inve~tigated,~~ along with equili-

(28) I I = 3 (29) n = 2

brium dialysis binding studies of the corresponding diphosphate (29) to these species.'O Myosin appears to hydrolyse (28) faster than ATP. a8

70

M. L. DePamphilis and W. W. Cleland, Biochemistry, 1973, 12, 3714. C. A. Janson and W. W. Cleland, J. Biol. Chem., 1974, 249, 2572. M. M. Werber, A. Oplatka, and A. Danchin, Biochemistry, 1974, 13, 2683.

H. Onishi, E. Ohtsuka, M. Ikehara, and Y. Tonomura, J. Biochem. (Japan), 1973, 74, 435. G. E. Willick, K. Oikawa, W. C. McCubbin, and C. M. Kay, Biochem. Biophys. Res. Comm., 1973, 53, 923.

153

Nucleo f ides and Nucleic Acids

The possible role of guanosine 3’-pyrophosphate-5’-triphosphate(30) in Although it can substitute for protein synthesis in E. coli has been GTP reactions catalysed by initiation factor (IF)2 and elongation factor 0

I

-0-P=O

I I -o---p=o 0

I

OH

(30) n = 3 (31) n = 2

(EF)T, (30) supports polyphenylalanine synthesis poorly. It is hydrolysed to guanosine-3’,5’-dipyrophosphate(31) by EF G and ribosomes. A chemical synthesis of (31) has been described.72 4 Oligo- and Poly-nucleotides

Chemical Synthesis.-Pursuit of a high-yield method for the synthesis of oligodeoxyribonucleotideson a polymeric carrier has led to the use of soluble y01ymers.~~~ 7 4 Thus, a copolymer of N-vinylpyrrolidone and vinyl acetate is formed and the ester groups are hydrolysed to give vinyl alcohol residues, to which the 5’-cNoroformate ester of the required terminal nucleoside is attached.73 The chain is built up by standard methods, the unconsumed reagents being dialysed away after intermediate steps. Cleavage from the polymer is effected with ammonia. Another liquid-phase method uses w,o‘-diaminopolyethylene glycol, the first nucleotide residue being coupled to the support as a phosphoramidate. The P-N bond is split with isoamyl nitrite after chain synthesis is completed. Other groups 76-77 have used insoluble macroporous styrene-divinylbenzene polymers substituted with trityl chloride groups to provide anchor points for the terminal nucleoside. Alternatively the chloro71 f1

?‘

76 76 77

E. Hamel and M. Cashel, Proc. Nat. Acad. Sci. U.S.A., 1973, 70, 3250. A. Simoncsits and J. Tomasz, Biochim. Biophys. Acta, 1974, 340, 509. H. Seliger and G . Aumann, Tetrahedron Letters, 1973, 291 1 . F. Brandstetter, H. Schott, and E. Bayer, Tetrahedron Letters, 1973, 2997. H. Koster and F. Cramer, Annalen, 1974, 946. H. Koster, A. Pollak, and F. Cramer, Annalen, 1974, 959. H. Sommer and F. Cramer, Chem. Ber., 1974, 107, 24.

154

Organophosphorus Chemistry

methylated polymer is treated with a 5’-phosphorothioate to form the 5’terminus,77cleavage after chain synthesis being effected with iodine. Protected nucleotide blocks can be used in the chain-lengthening process.7S~T 6 If a large, non-polar moiety is used as a protecting group for terminal phosphate in oligonucleotide synthesis, a degree of solubility in organic solvents is conferred on the initial intermediate compounds, facilitating isolation. 9-Hydroxymethylfluorene (32) has been used for this purpose.78

Q(

CHN,

I

-0

~H,OH (32)

(33)

Nucleotides in aqueous solution can be alkylated at the phosphate (and in some cases the nucleoside also) by the action of 1-0xidopyridin-2-yldiazomethane The protecting group may be removed from the phosphate with snake venom phosphodiesterase, or generally by acetic anhydride treatment, followed by ammonia. Phosphoramidates have been described previously as phosphate-protecting groups, and if 2-naphthylamine is used as its anilidate for this purpose, organic solvent extraction (as above) is possible.81 A variation on this theme is to use dianilidophosphochloridate (34) as a (33).789

Q NH

c1 (34)

phosphorylating agent,82 the bisanilidate triesters thus formed being deprotected with arnyl nitrite. N-Trityl-4-aminophenol has also been used for terminal phosphate protection.83Again, solvent extraction of intermediates is possible. The group is removed by aqueous iodine, and the putative mechanism (Scheme 2) is reminiscent of the oxidation of hydroquinone phosphates and suggests that this reaction may also be used for phosphorylation.

‘O

*I

N. Katagiri, C. P. Bahl, K. Itakura, J. Michniewicz, and S. A. Narang, J.C.S. Chem. Comm., 1973, 803. T. Endo, K. Ikeda, Y. Kawamura, and Y. Mizuno, J.C.S. Chem. Comm., 1973, 673. Y. Mizuno, T. Endo, T. Miyaoka, and K. Ikeda, J. Org. Chem., 1974,39, 1250. E. Ohtsuka, A. Honda, H. Shigyo, S. Morioka, T. Sugiyama, and M. Ikehara, Nucleic Acid Res., 1974, 1, 223. J. Smrt, Tetrahedron Letters, 1973, 4727. E. Ohtsuka, S. Morioka, and M. Ikehara, J. Amer. Chem. SOC.,1973, 95, 8437.

155

Nucleotides and Nucleic Acids 0 TrNH-(-)--O-y--OR

w

II I

-0

Tr = Trityl R = 5'-ribofuranosylnucleoside

0

II 1 OH

RO-P-OH

H2O

Scheme 2

Arylsulphonyl 1,2,4-triazolides (35), prepared from the appropriate arylsulphonyl chloride and 1H-1,2,4-triazoleYcan be used to activate phosphomonoesters or -diesters for condensation reactions in polynucleotide synthesis. 84 Yields for condensations involving guanosine residues are better than those obtained using aryl sulphonyl chlorides.

R (35) R = MeorPri

The synthesis of tRNA fragments has been reviewed.86 Most reports concerning synthesis of sizeable oligoribo-8u or oligodeoxyribo-nucleotides which have appeared have used the block condensation methods defined by Khorana. However, the anticodon loop of E. coli tRNAMethas been synthesized using the triester method.02In this procedure, previous prao tice has been to condense a protected nucleoside bearing a free 3'-hydroxygroup with the monophosphate of a subsequently removable protecting group (phenyl, trichloroethyl, 2-cyanoethyl), and to condense the resulting B4

N. Katagiri, K. Itagura, and S . A. Narang, J.C.S. Chem. Comm., 1974, 325. M. Ikehara, Accounts Chem. Res., 1974,7, 92. E. Ohtsuka, M. Ubasawa, S . Morioka, and M. Ikehara, J. Amer. Chem. Soc., 1973,95, 4725.

89

9=

M. S. Poonian, E. F. Nowoswiat, L. Tobias, and A. L. Nussbaum, Bio-organic Chem., 1973, 2, 322. M. T. Doe1 and M. Smith, F.E.B.S. Letters, 1973, 34, 99. R. Padmanabhan, E. Jay, and R. Wu, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 2510. H. Schott and H. Kossel, J. Amer. Chem. Soc., 1973, 95, 3778. R. Wu, C. D. Tu, and R. Padmanabhan, Biochem. Biophys. Res. Comm., 1973,55,1092. T. Neilson and E. S . Werstiuk, J. Amer. Chem. Sac., 1974, 96, 2295.

Organophosphorus Chemistry

156

phosphodiester with the 5’-hydroxy-group of another protected nucleoside. However, cleaner reactions and better yields are obtained if the triester is formed subsequent to the establishment of the internucleotidic link. Treatment of the phosphodiester with TPS and 2-cyanoethanol93s 9 4 or 2,2,2-trichloroethanol 96 gives the phosphotriester quantitatively. In deoxyoligonucleotide synthesis, 2-(phenylthio)ethanol has been used.g*It is removed by treatment with periodate and alkali. Nucleoside 0-phosphorothioates react with acrylonitrile at pH 8-9 to give S-cyanoethyl derivatives, which may then be condensed with other nucleosides.D7 Treatment with ammonia eliminates the cyanoethyl group, giving a dinucleoside 0,O-phosphorothioate. A number of these compounds, including 98 TpSTpST,have been Enzymatic Synthesis.-A number of homopolynucleotidescontaining atypical bases or sugars have been ~ r e p a r e d6 v. ~ ~gg-104 In each case the corresponding nucleoside-5’-diphosphatewas polymerized with polynucleotide phosphorylase. The polymers have largely been studied with respect to the effect of the modification on single-strand stacking and on the ability to form helical selfstructures and duplexes with complementary polynucleotides. Thus, p0ly-(8bromoadenylic acid), in which the base has the syn conformation, forms a stable helical self-structure, but does not interact with p ~ l y ( r U ) In . ~ com~~ parative studies on poly (2’-O-alkyladenylic acids) it is found that base stacking decreaseslo6 but helical self-structure is stabilizedlo’as the size of the alkyl group increases, presumably owing to the steric requirements imposed. Single-stranded heteropolymers containing some 2’-O-methyl nucleotides are hydrolysed by exoribonuclease much more slowly than similar polymers containing only ribose residues, and hence it is suggested that 2’-O-methylation is used in the cell to stabilizeribosomal RNA sequences, prior to processing.lo6 ApAp and ApApAp are converted into the cyclo-oligonucleotideson treatment with DCCD.loSC.d. measurements show a different conformation from the linear compounds, which is probably dictated by backbone structural 6p

** K.:Itakura, C. P. Bahl, N. Katagiri, J. J. Michniewicz, R. H. Wightman, and S. A Narang, Canad. J. Chem., 1973, 51, 3649. J. Smrt, Coll. Czech. Chem. Comm., 1973, 38, 3189. ‘ I J. Smrt, Coll. Czech. Chem. Comm., 1973, 38, 3642. *’ J. Smrt, Coll. Czech. Chem. Comm., 1974, 39, 972. O7 A. Malkievicz and J. Smrt, Coll. Czech. Chem. Comm., 1973, 38, 2953. @*J. Smrt and A. Malkievicz, Coll. Czech. Chem. Comm., 1973, 38, 2962. s* F. Ishikawa, J. Frazier, and H. T. Miles, Biochemistry, 1973, 12, 4790. l o o J. 0. Folayan and D. W. Hutchinson, Biochim. Biophys. Acta, 1974, 340, 194. lol J. 0. Folayan and D. W. Hutchinson, Tetrahedron Letters, 1973, 5077. lo¶ M. A. W. Eaton and D. W. Hutchinson, Biochim. Biophys. Acta, 1973, 319, 281. l o $ P. F. Torrence, A. M. Bobst, J. A. Waters, and B. Witkop, Biochemistry, 1973,12,3962. lo‘ J. T. Kusmierek, M. Kielanowska, and D. Shugar, Biochem. Biophys. Res. Comm., *I

1973, 53, 406.

F. B. Howard, J. Frazier, and H. T. Miles, J. Biol. Chem., 1974, 249, 2987. l o ( J. L. Alderfer, I. Tazawa, S . Tazawa, and P. 0. P. T’so, Biochemistry, 1974,13, 1615. l o ? F. Rottman, K. Friderici, P. Comstock, and M. K. Khan, Biochemistry, 1974,13,2762. lo* S . E. Stuart and F. M. Rottrnan, Biochem. Biophys. Res. Comm., 1973, 55, 1001. l o oE. Ohtsuka, H. Tsuji, and M. Ikehara, Chem. andPharm. Bull. (Japan), 1974,22, 1022 loo

Nucleotides and Nucleic Acids

157

requirements rather than base stacking. Two new repeating trinucleotide DNA complexes, d(T-C-Qn - d(G-G-A)n110 and d(A-A-T)n d(A-T-T),,ll1 have been reported. The trinucleotide segments are polymerized chemically to form short chains, which are then used as templates for DNA polymerase I. If thymidine-5’-phosphate is polymerized in the presence of N 6 , 0 2 ’ , 0 3 ’ triacetyladenosine using TPS, and the resulting mixture treated with ammonia and passed over dihydroxyborylcellulose, a series of oligonucleotides (pdT)%pAcan be isolated. These can then act as primers for polynucleotide phosphorylase, and with ADP a series of compounds (pdT)n(pA)n is prepared, model substrates for studyingthe action of nucleases on polynucleotides containing hybrid sequences.112 Single-stranded DNA can be extended at the 3’-terminus using terminal deoxynucleotidyl transferase; with dCTP as substrate, a poly(dC) adduct is formed. This can be annealed to poly(r1)Sephadex, and forms the basis of a new technique for isolating DNA-RNA hybrids. The enzyme tRNA nucleotidyl transferase may be used to incorporate 5’triphosphates of adenosine analogues into the -CpCpA end of tRNA, and 2’- and 3’-deoxyadenosine have been thus inserted into yeast tRNAPhe. Only the tRNA with the 3’-dA terminus is chargeable with phenylalanine, i.e. a substrate for yeast phenylalanyl tRNA synthetase, but the charged tRNAPhe-3’-dA will not act as acceptor for a growing polynucleotide chain in the peptidyl transferase reaction. 11* However, 3’-aminoacylated tRNAPh@carrying 3’amino-3’-deoxyadenosine at the terminus will act as acceptor. 116It thus seems that in protein synthesis, tRNA is first aminoacylated on the terminal adenosine at the 2’-position, and 2’-+3’ transacylation then takes place, the 3’acylated species then acting as acceptor in chain elongation. Similar conclusions 116have been drawn from studies on CpA analogues containing 2’- or 3’-O-methyladenosine, in which the remaining free adenosine hydroxy-group was aminoacylated. Sequencing.-The technique of polynucleotide sequencing by continuous directional degradation, in which incubation with alkaline phosphomonoesterase and periodate gives sequential release from the 3’-end of nucleoside dialdehydes, which are reduced with borotritide and identified chrornatographically, has been refined at micromolar concentrations,117and a better A. R. Morgan, M. B. Coulter, W. F. Flintoff, and V. H. Paetkau, Biochemistry, 1974, 13, 1596. 111 R. L. Ratliff, D. L. Williams, F. N. Hayes, E. L. Martinez, jun., and D. A. Smith, Biochemistry, 1973,12, 5005. T.F. McCutchan and P. T. Gilham, Biochemistry, 1973, 12, 4840. 11* J. M. Coffin, J. T . Parsons, L. Rymo, R. K. Haroz, and C. Weissmann, J. MoZ. Biol., 1974,86, 373. 11* M. Sprinzl and F. Cramer, Nature New Biol., 1973,245, 3. llP T .H.Fraser and A. Rich, Proc. Nat. Acad. Sci. U.S.A., 1973,70, 2671. ll6 S. Chladek, D. Ringer, and K. Quiggle, Biochemistry, 1974, 13, 2727. 11’ K.Randerath, R. C. Gupta, E. Randerath, and L. S. Y. Chia, F.E.B.S. Letters, 1973,36, 301.

158

Organophosphorus Chemistry

mapping procedure described.118 In a new method for fingerprinting nonradioactive RNA,lle cleavage with T,RNAse and dephosphorylation with alkaline phosphatase reduce the molecule to oligonucleotide fragments with guanosine at the 3’-termini. These are used as primers for polynucleotide phosphorylase using [CZ-~~PIGDP as substrate, in the presence of TIRNAse,thus labelling all terminal 3’-hydroxy-residues with radioactive phosphate. The fragments are separated and treated with spleen phosphodiesterase (a 5’exonuclease), and the sequential degradation products analysed by mobility shifts on a two-dimensionalmap obtained by homochromatographicmethods. Alternatively, fragments produced by pancreatic RNAse digestion can similarly be labelled using [cx-~~PIUDP and polynucleotide phosphorylase. 5’-End labelling of fragments with polynucleotide kinase and sequential degradation from the 3’-end with snake venom phosphodiesterase allows the sequence data to be checked. Similar methods have been used for DNA sequence analysis.12oT4Polynucleotide kinase quantitatively phosphorylates oligodeoxyribonucleotides at the 5’-nucleoside, even if N-protecting groups are present, and may thus be synthetically The 3’-end regions of RNA may be isolated by T,RNAse cleavage, and isolation of the cis-diolbearing fragments may be achieved using dihydroxyborylcellulose.122 The fragments may then be labelled and analysed as described above. Treatment of the guanine bases in oligoribonucleotides with kethoxal (8-ethoxy-a-ketobutyraldehyde) protects the chain from cleavage by T2RNAse adjacent to these residues 123 and may be used to detect poly(rG) sequences and determine (GP)~XPratios 124 in chain analysis. 5 Analytical Techniques and Physical Methods

Molecular Weights.-Polyacrylamide gel electrophoresis of poly(rA) has been described as a rapid method for molecular weight deter1ninati0n.l~~ A new method of molecular weight determination in nucleic acids relies on endphosphate analysis.les Monoesterified phosphate is removed from the polynucleotide enzymatically and isolated quantitatively. Then this sample, and that obtained by hydrolysis of the remainder of the polynucleotide, are subjected to simultaneous neutron activation, and the ratios of 32P thus formed give the molecular weight (in conjunction with base analysis data). Chain lengths up to 3.6 x lo4 residues can be estimated, and agreement with values obtained by sedimentation is reasonable. Although facilities to practice K. Randerath, E. Randerath, L. S. Y.Chia, and B. J. Nowak, Analyt. Biochenz., 1974, 59,263. l l B K. S. Szeto and D. So11, Nucleic Acid Res., 1974, 1, 171. l a 0 E. Jay, R. Bambara, R. Padmanabhan, and R. Wu, Nucleic Acid Res., 1974, 1, 331. l a l J. H. van de Sande and M. Bilsker, Biochemistry, 1973, 12, 5056. 11’ M. Rosenberg, Nucleic Acid Res., 1974, 1, 653. lBa T. A. Avdonina and L. L. Kisselev, Mol. Biol. Reports, 1974, 1, 283. I a 4 T. A. Avdonina and L. L. Kisselev, F.E.B.S. Letters, 1974, 39,283. l a 6J. C. Pinder and W. B. Gratzer, Biochim. Biophys. Acta, 1974, 349, 47. I*( L. Clerici, E. Sabbioni, F. Campagnari, S. Spadari, and F. Girardi, Biochemistry, 1973, 12, 2887. 118

Nucleotides and Nucleic Acids

159

this method are somewhat limited, it is valuable for those polynucleotides in which the partial specific volume (required with sedimentation data for a molecular weight) is likely to differ appreciably from normal values. Separation.-Double-stranded DNA is adsorbed more strongly on hydroxyapatite than double-stranded RNA or DNA-RNA hybrids, in which the phosphate groups stick out less from the helix. This forms the basis of a fractionation method.127On eluting double-strandedDNA, strands containing a higher proportion of G-C base pairs are eluted earlier, and use of a basespecific intercalating agent can improve this resolution. 12*Single-stranded poly(rA) and single-stranded DNA bind to cellulose at high ionic strength.129 Poly(rA) may then be specifically eluted with poly(rU), which constitutes a useful separation for poly(rA) tracts. The use of high-performance liquid chromatography on reversed-phase columns at elevated pressures is becoming increasingly popular for separating nucleic acid constituents at subnanomole levels,130 and, for example, oligonucleotide condensation 131 and the reaction of hexokinase with ATP and analogues132have been studied by this technique. Structure Probes.-The introduction of fluorescing labels into nucleic acids can yield valuable structural information, and both organic compounds 133-135 and metal ions Pb1I1 (ref. 136) and EuIII (ref. 137)] have been used as fluorescent probes for tRNA 134*13' and other polynucleotides. The degree of secondary structure in RNA has been estimated from Raman scattering by the phosphate group ~ i b r a t i 0 n s . lA~ ~ number of lH n.m.r. studies have appeared, but discussion of these is more suited to a review on lH n.m.r. spectroscopy. Lanthanide ions have been used as contact shift reagents to probe tRNA structure.139 133p

H. G. Martinson, Biochemistry, 1973, 12, 2737. W. Pokroppa and W. Muller, Proc. Nut. Acad. Sci. U.S.A., 1974, 71, 699. l a g P. A. Kitos and H. Amos, Biochemistry, 1973, 12, 5086. l P 0 C. Horvath, Methods Biochem. Analysis, 1973, 21, 79. lS1 A. F. Cook, A. de Czekala, T. F. Gabriel, C. L. Harvey, M. Holman, J. E. Michaelewsky, and A. L. Nussbaum, Biochim. Biophys. Acra, 1973, 324,433. l a p K.-W. Stahl, E. Schlimme, and F. Eckstein, F.E.B.S. Letters, 1974, 40,241. 188 A. Maelicke, M. Sprinzl, F. von der Haar, T. A. Khwaja, and F. Cramer, European J. Biochem., 1973,43, 617. la4 S. A. Reines and C. R. Cantor, Nucleic Acid Res., 1974, 1, 767. F. Pochon and M. Perrin, European J . Biochem., 1974, 43, 107. 1 8 0 C. Formoso, Biochem. Biophys. Res. Comm., 1973, 53, 1084. lS7 J. M. Wolfson and D. R. Kearns, J. Amer. Chem. SOC.,1974, 96, 3653. l P 8 G. J. Thomas, jun. and K. A. Hartman, Biochim. Biophys. Acta, 1973, 312, 31 1. l p S C. R. Jones and D. R. Kearns, J. Amer. Chem. SOC., 1974,96, 3651. la'

laB

9 Ylides and Related Compounds BY S. TRIPPETT

1 Methylenephosphoranes Preparation.-A historical account of the development of the synthesis of methylenephosphoranes has been given.l Details have appeared 2* of the use of epoxides in the generation of ylides from phosphonium salts. Weakly acidic salts are deprotonated by the anions such as XCH,CH20- formed by attack of the phosphonium counter-anion on epoxide, but strongly acidic phosphoniun salts are deprotonated more rapidly than these species are produced.2The base in these cases must be either epoxide or original anion. Side-reactions in olefin syntheses using epoxides as base include acetal formation from aldehyde and epoxide, cyclopropane formation from ylide and epoxide, and decomposition of quinquecovalent phosphoranes, e.g. (l), formed from phosphonium salt and

epoxides. In general, these competing reactions are slower than. olefin synthesis. Meclinnism. Additional evidence is appearing that Reactions.-CCavbonyfs. 1,Zoxaphosphetans are formed directly from ylides and carbonyl compounds. Further studies on the kinetics of the reactions of phenacylidenetriphenylphosphoranes with substituted benzaldehydes in non-polar aprotic solvents and in glycols support the concept of a highly oriented transition state of low polarity. 31Pn.m.r. spectroscopy on solutions in which ylides and carbonyl compounds had been allowed to react at - 70 "Cshowed the presence of only 49

G. Wittig, Accounts Chem. Res., 1974, 7 , 6 . J. Buddrus and W. Kimpenhaus, Chem. Ber., 1974,107, 2062. a J. Buddrus, Chem. Ber., 1974, 107, 2050. N. A. Nesmeyanov, E. B. Binshtok, and 0. A. Reutov, DokZady Chern., 1973,210,499.. * G. Aksnes and F. Y . Khalil, Phosphorus, 1973, 3, 79. G. Aksnes and F. Y . Khalil, Phosphorus, 1973, 3, 109.

160

Ylides and Related Compounds

161

+

1,2-0xaphosphetans.~Orthogonal approach of the reactants, i.e. J12a n2s, has been suggested. This would lead to the more sterically hindered 1,2oxaphosphetan and hence to cis-olefin, as found in general under conditions in which the first stage is irreversible. CNDO-MO calculations suggest that the Wittig olefin synthesis proceeds via 1,2-oxaphosphetans, which undergo P -C bond cleavage considerably in advance of P-0 bond cleavage. A fine balance between steric and electronic efiects in attempted olefin synthesis in protic solvents has been revealed in experiments involving furyland pyrrolyl-phosphonium salts. Thus although the salt (2; R = Ph) gave a ,~ high yield of styrene with benzaldehyde in ethanoIic ethoxide s o l ~ t i o n the t-butyl salt (2; R = But) under the same conditions gave the styrylphosphine

(5)

(4)

oxide (3) as the major product.1° Similarly the pyrrolylphosphonium salt (4) gave the phosphine oxide (3, although styrene was the major product from the corresponding tri(2-fury1)phosphonium salt. Reaction at y-position of nllylic ylides. More examples are appearing in which allylidenephosphoranesundergo reaction at the y-position. The allylidenephosghorane (6), generated using DBU, with benzaldehyde in refluxing THF gave ph;P=CH--cH=----cH, (6)

+ PhCHO /

\

PhCH=CH-CH=C& P&H==CHCH~CH(OH)P~

(7) DBU1

PhCH=CH-CH=CHCH(OH)Ph

< PhCHo

Ph,P=CH-CH=CHCH(OH)Ph

(8)

' E. Vedejs and K. A. J. ' llo

Snoble, J. Amer. Chem. SOC.,1973, 95, 5778. C. Trindle, J.-T. Hwang, and F. A. Carey, J. Org. Chern., 1973, 38, 2664. D. W. Allen, B. G. Hutley, and T. C. Rich, J.C.S. Perkin IZ, 1973, 820. D. W. Allen, P. Heatley, B. G. Hutley, and M. T. J. Mellor, Terruhedron Letfers, 1974, 1787.

162

Organophosphorus Chemistry

the expected diene and the alcohol (8), probably formed via the salt (3." In methanol, the alcohol (8) was the major product. a- and y-Condensations also occurred in the reaction of the phosphorane (9) with hexanal, leading to the dienes (10) and (11) respectively.12The latter could have been formed via the

+ C,H, ,CHO

Ph,P=CH-CMe=CHCO,Me

-+ C,H, ,CH=CH-CMe=CHCO,MI

(9)

(12)

six-membered phosphorane (12). The ratio of a- to y-condensation varied, and conditions were defined leading to > 90 % of one or the other. The formation of a cyclohexa-1,3-dienefrom an &unsaturated ketone and an allylidenephosphorane,first noted by BUchi,l3 has been extended l4*l6 to a general synthesis of these compounds (see Scheme l), and other examples have

Po f

y

n

_If

3

GiPh3 + X

X

X

J.

X = H, CO,Me, CONC,H,,, CN

y+

Ph,PO

X Scheme 1

been reported.16Cyclic afl-unsaturatedketones lead in the same way to bicyclic dienes, which may be highly strained.17 That from cyclopentenone was l1

l4 l6

l7

E. Vedejs, J. P. Bershas, and P. L. Fuchs, J . Org. Chew., 1973, 38, 3625. E. J. Corey and B. W. Erickson, J. Org. Chem., 1974, 39, 821. G. Buchi and H. Wuest, Helv. Chim. Acta, 1971, 54, 1767. F. Bohlmann and C. Zdero, Chem. Ber., 1973, 106, 3779. W. G. Dauben, D. J. Hart, J. Ipaktschi, and A. P. Kozikowski, Tetrahedron Letters, 1973, 4425. A. Padwa and L. Brodsky, J. Org. Chem., 1974,39, 1318. W.G.Dauben and J. Ipaktschi, J. Amer. Chem. SOC.,1973, 95, 5088.

163

Ylides and Related Compowzdr

8

+ Ph,P=CH-CH=CH,

__f

trapped as the adduct (13) with furan. Increasing y-substitution in the allylidenephosphorane inhibits y-condensation,ll, l6 as exemplified in Scheme 2.

R

m

=y

+ Ph,P=CH-CH=CR,

25%

R=M&

Scheme 2

Similar y-condensations of allylidenephosphoranes involving Michael addition to conjugated dienoic esters lead to bicyclo[4,1,O]heptanes, as shown in Scheme 3.18 General. A number of olefin syntheses have been carried out in aqueous 2o Thus isopropyltriphenylphosphonium solution or in two-phase iodide and benzaldehyde in methylene chloride50 % aqueous sodium hydroxide gave 30% of the olefin (14).20 W. G. Dauben and A. P. Kozikowski, Tetrahedron Letters, 1973, 371 1. M. Butcher, R. J. Mathews, and S. Middleton, Austral. J. Chem., 1973, 26, 2067. G . Mark1 and A. Merz, Synthesis, 1973, 295.

lU

lo *O

164

Organophosphorus Chemistry

R

R

R

R

R Scheme 3

Ph3kHMe, I-

+ PhCHO

>&?i!:2H

PhCH-CMe, (14)

Undesirable side-reactions in olefin synthesis can often be avoided by judicious choice of conditions. Problems associated with epimerization in methylenation of the diastereoisomeric aldehydes (15) and (16) were overcomea1 by using DMSO as solvent at low temperature, with an excess of Me

Me

I

I

H H

I

H (16)

H

phosphonium salt and potassium rather than sodium dimsylate. Scrambling of deuterium in the synthesisof the olefins RCH= CD, using trideuteriomethyltriphenylphosphonium iodide was avoided 2 2 by using t-butyl-lithium as base and quenching the reaction mixtures with D20. Among aldehydes used successfully in olefin synthesis are glyoxal (in the p1

V. Ark, J. M. Brown, and B. T. Golding, J.C.S. Perkin ZI, 1974, 700.

4s

G. W. Buchanan and A. E. Gustafson, J. Org. Chem., 1973, 38, 2910.

165

Ylides and Related Compounds 0

H

(EtO),CHCHO

CH,=CH CMe(0Ac)CH,CHO

Ph,kHRCHO Br-

(20)

(21)

form of trimeric glyoxal d i h ~ d r a t e )the , ~ ~protected glyoxals (17) and (18),24 5-(formylmethyl)uracil (19),25the acetate (20),28the phosphonium salts (21),27 and the cyclopropylaldehyde (22). 2 8 De-formylation is a problem with some

+

Ph,P=CHR

-+

nickel-porphyrin meso-aldehydes.29 Further examples have appeared 30 of the synthesis of trans-olefins via the stereospecific protonation of p-oxido-ylides. Many S-polyketones have been methylenated to give 6-polyenes.s1 Although the cyclohexadienone (23) with methylenetriphenylphosphorane gave the expected triene, the isomeric ketone (24) somewhat surprisingly failed to react. Reactive ylides absorb carbon dioxide to give betaines (25), which on ps 24

26 *6

Pf

s8 a0

ao

G. Kossmehl and B. Bohn, Chem. Ber., 1974,107, 710. A. I. Meyers, R. L. Nolen, E. W. Collington, T. A. Narwid, and R. C. Strickland, J. Org. Chem., 1973, 38, 1974. D. E. Bergstrom and W. C. Agosth, Tetrahedron Letters, 1974, 1087. F. Bohlmann and D. Kornig, Chem. Ber., 1974,107, 1780. M. Le Corre, Tetrahedron Letters, 1974, 1037. J. P. Marino and T. Kaneko, Tetrahedron Letters, 1973, 3975. H. J. Callot, Bull. SOC.chim. France, 1973, 3413. R. L. Markezich, W. E. Willy, B. E. McCarry, and W. S. Johnson, J . Amer. Chem. SOC., 1973,95, 4414.

a1

J. Ferard, M. Keravec, and P.-F. Casals, Compt. rend., 1973, 277, C, 1261. L. A. Paquette, R. P. Henzel, and R. F. Eizember, J. Org. Chem., 1973, 38, 3257.

OrganophosphorusChemistry

166

6 alkaline hydrolysis followed by acidification give carboxylic acids.33 Thermolysis of the betaines leads either to the phosphoranes (26) when R1 = H or to the allenes (27), ketens being the probable intermediates.

a

Ph,P=CRLR2 + CO, ---+ Ph,kR1R2CO;

y \ ;f5)

Ph,P=C RZCOCH,R2

R',R*

A

#

Ph,PO + R'R2CHC0,H

M

R' R2C=C=CR1

(26)

R2

(27)

The formation of acrylonitriles from the reaction of dihalogenomethylenephosphoranes with aroyl cyanides has now been extended34 to include the use of aliphatic acyl cyanides, although the conditions need to be closely defined. Perfluoroisocyanates with diphenylmethylenetriphenylphosphorane give the expected keten-imines(28) or their rearrangement products (29).3sFormylation of both reactive and stable ylides has been achieved using the mixed anhydride of formic and acetic (CFS)&NCO

-IPhsP--zPn2

*

(CF,XCN=C=CPh, (28) 72%

CF,CF,CF,NCO + Ph,P=CPh,

+ CF,CF,CF=N-CF=CPh,

(29) 92%

Ylides are intermediates in the synthesis of dihydrothi~phens,~~ as shown in Scheme 4, and of a range of heterocycle^,^^ e.g. (31), using the cyclopropylphosphonium salt (30) as shown in Scheme 5. 88

s6

H. J. Bestmann, J. Denzel, and H. Salbaum, Tetrahedron Letters, 1974, 1275. B. A. Clement and R. I. Soulen, J. Org. Chem., 1974, 39, 97. D. P. Del'tsova, N. P. Gambaryan, and I. L. Knunyants, Doklady Chem., 1973,212,767. J. M. McIntosh and H. B. Goodbrand, Tetrahedron Letters, 1973, 3157. P. L. Fuchs, J. Amer. Chem. SOC.,1974, 96, 1607.

I67

Ylides and Related Compounds + R'COCRzR3SH -t F'h,PCH=CH,

Br- --+

Scheme 4

O C H O N PPh3 H

.

O C 0 2 E t

B C 0 , E t (31)

92%

Scheme 5

Miscellaneous. Tetramethylphosphonium salts have been generated from methylenetrimethylphosphoraneby treatment with acid in inert solvent, or with ammonium salts in inert solvents or in aqueous ethanoLs8Details have appeared of the preparation of By-unsaturated ketones using lithiated phenacylidenetriphenylphosph~rane.~~ Alkylation of the metallated ylide (32) has

=

Ph,P=CHCOCH3 -78°C

Ph,P=CHCOCH,Li (32) k"d

Ph,PO + RCH,COCH3

Hzo

Ph,P-CHCOCH,R

now been applied in a general synthesis of the ketones RCH2COCHs.40The ylide (33) can be similarly metallated and subsequently alkylated on one or 88

40

H. Schmidbaur and H. Stuhler, 2.anorg. Chem., 1974, 405, 202. C . Broquet, Tetrahedron, 1973, 29, 3595. M. P. Cooke,jun., J . 0 - g . Chem., 1973,38,4082.

Organophosphorus Chemistry

168 /CoCH2Li

Ph,P=C

/cOCHzR

“’

A Ph,P=C

‘COCH3

Ph,P=C(COCH,

l2

Y

‘cwH3/

x Ph,P=C(COCH,Li),

(33)

iii

-% Ph,P=C(COCH,R),

(34)

27

Ph3P

(35) 25% Reagents: i, 1 RW; ii, 2 R U ; iii, 1 RHal; iv, 2 RHal; v, (CH&.

Scheme 6

both of the methyl groups, as shown in Scheme 6.*l Although no identifiable products were obtained from the dimetallated ylide (34) and di-iodomethane or 1,2-dibrornoethaney treatment with 1,3-di-iodopropane gave the eightmembered phosphorane (35). A full account has appeared of the alkylation of the ester phosphorane Ph3P= CHCOzEtwith triethyloxonium borofluoride and of the reactions of the resulting ylide PhBP=C= C(OEt)2.42The cumulated phosphoranes (36) and 3Ph3P=CH2

+ RN=CCl,

3Ph,P=CH,

+ Cl$S

-

__f

+

+ 2Ph,PCH3Cl-

Ph,P=C=C=NR (36) 70-80%

+

Ph,P=C=C=S

+ 2Ph3PCH3Cl-

(37) 60% (37) have been obtained from methylenetriphenylphosphorane and isocyanide dichlorides and thiophosgene, respectively. Further examples have appeared of the formation of A3-pyrrolinesfrom the PhCH-

C(CO,Me),

‘d Ph

(38) 41

‘1

f

Ph,P=CHCOPh

+ Ph,PO

--+ Ph (39)

M. P. Cooke,jun., and R. Goswami, J. Amer. Chem. SOC.,1973, 95, 7891. H. J. Bestmann, R. W. Saalfrank, and J. P. Snyder, Chem. Ber., 1973, 106, 2601. H. J. Bestmann and G. Schmid, Angew. Chem. Internat. Edn., 1974,13, 273.

169

Ylides and Related Compounds

reaction of stable phosphoranes with a ~ i r i d i n e sThe . ~ ~ A3-pyrroline(39) was the unexpected product from the aziridine (38) and phenacylidenetriphenylphosphorane; it is not clear how it is formed. A3-Pyrrolineswere also obtained from phosphoranes and the oxazolidine (40).

(40)

Methylenetrimethylphosphorane with mercury(@ chloride and methylmercury chloride gave the salts (41) and (42), respectively, from which it was Me,kH,HgCH,;Me,

2Cl-

(41) Me,P==CH,

Me,kH,HgMe

C1'

(42)

not possible to generate the corresponding y l i d e ~ However, .~~ the mercurycontaining ylide (43) was obtained as shown in Scheme 7. Details have Me,P=CHSiMe,

+ MeHgCl

--+Me,kH(SiMe,)HgMe

C1'

I?(c,P=CHSiMc,

Me,P(CH,Li)=CHSiMe,

+ MeHgCl --+

Me,P=C(SiMe,)HgMe

(43) Scheme 7

appeared of the reactions of ylides with the complexes Mn(CO),Br and Rh(C0)6Br,46and complexes of methylenetrimethylphosphorane with nickel alkyls have been described.*' The interesting complexes (44),48(45),4g and (46)4 9 have been prepared using ylides as shown in Scheme 8. 44

M. Vaultier, R. Danion-Bougot, D. Danion, J. Hamelin, and R. Carrie, Compt. rend., 1973, 277, C, 1041.

46 46

H. Schmidbaur and K.-H. Rathlein, Chem. Ber., 1974, 107, 102. W. C. Kaska, D. K. Mitchell, R. F. Reichelderfer, and W. D. Korte, J. Amer. Chern. SOC.,1974, 96, 2847.

47

4B

H. H. Karsch, H.-F. Klein, and H. Schmidbaur, Chem. Ber., 1974, 107, 93. H. H. Karsch and H. Schmidbaur, Angew. Chem. Internat. Edn., 1973, 12, 853. E. Kurras, U. Rosenthal, H. Mennenga, and G. Oehme, Angew. Chem. Internat. Edn., 1973, 12, 854.

Organophosphorus Chemistry

170

NppM Ni

Ph,P=CH,

+ Ph,Cr(THF),

CH2

$I ‘PPh,

\ I (45)

2 Phosphoranes of Special Interest The product obtained from triphenylphosphine and periluorocyclobutene has been shown by X-ray analysis to be the ylide (47).60 The same technique has

li0

M. A. Howells, R. D. Howells, N. C . Baenziger, and D. J. Burton, J. Amer. Chem. Soc., 1973,95, 5366.

171

Ylides and Related Compounds

shown that the ylide (48) is not linear,s1 the PCC bond angle being 125.6".

This ylide, with the diones (49), gave the allenes (SO), isolated as such when X = CH2 but dimerizing when X = 0.62

+

II

PPh, (51) R = HorBr

The fluorenylidenephosphoranes (5 l), which had not previously been observed to react with ketones, reacted exothermically with the central carbonyls of the triones (52) and (53) to give the corresponding olefins,6s Photoelectron spectroscopy and X-ray analysis suggest that the phos, ~ agreement ~ phorane (54) has 20% of ylene and 80% of ylide c h a r a ~ t e r in with previous calculations. Phosphorane (54) couples with benzaldehyde in

-fi3€'a+ ==? I

(54)

F'hCHO

Ph3P

CH(0H)Ph

(55)

THF at room temperature to give the alcohol (55),55 emphasizing the susceptibility of (54) to electrophilic substitution at the 2-position. A kinetic investigation of the base-catalysed reaction between (54) and the cyano-olefin (56) led to the postulate of a reversible first stage, with an Elcb elimination from the intermediate (57) via an ion-pair involving hydrogen bonding between the conjugate acid of the base and the departing cyclohexyloxy-anion.66 I1 bB

64

H. Burzlaff, U. Voll, and H. J. Bestmann, Chem. Ber., 1974, 107, 1949. R. W. Saalfrank, Tetrahedron Letters, 1973, 3985. A. Schonberg, E. Singer, and H. Schulze-Pannier, Chem. Ber., 1973, 106, 2663. H. L. Ammon, G. L. Wheeler, and P. H. Watts, jun., J. Amer. Chem. SOC.,1973, 95, 6158.

s6

2. Yoshida, S. Yoneda, and Y. Murata, J. Org. Chem., 1973,38, 3537. M. P. Naan, A. P. Bell, and C. D. Hall, J.C.S. Perkin ff, 1973, 1821.

Organophosphorus Chemistry

172

(5 7)

p

n3p?

+

C(CN)=C(CN), C,H1loH

The betaines (58) did not react with benzaldehydeeven in refluxing DMSO, but with other electrophiles they reacted readily on the central nitrogen.57

-

Thermolysis of the tungsten-ylide complex (59) in cyclohexene gave the hydrocarbon (60),perhaps via the carbene C20.58 W(CO),(MeCN) + Ph3P=C=C0

(OC),WC(Pph,)=CO (59)

(60) No evidence was found for the phenolic form (62) in the i.r. and n.m.r. spectra of the diphosphacyclohexadienone(61).59The triboluminescenceof the phosphorane Ph3P= C = PPhs has been investigated.60

s7

Y.Tanaka and S. I. Miller, J. Org. Cliem., 1973, 38, 2708.

OD

H. Berke and E. Linder, Angew. Chem. Znternat. Edn., 1973, 12, 667. T. A. Mastryukova, K. A. Suerbaev, E. I. Fedin, P. V. Petrouskii, E. I. Matrosov, and M. I. Kabachnik, J. Cen. Chem. (U.S.S.R.), 1973, 43, 1185. J. I. Zink and W. C. Kaska, J. Amer. Chem. SOC.,1973, 95, 7510.

Ylides and Related Compounds

173

3 Selected Applications of Ylides in Synthesis General.-A synthesis of ag-unsaturated aldehydes uses the ylide from the salt (63) followed by hydrolysis of the resulting acetals.61 Vinyloxazines (65),

P

Ph3kH2CF$

Bf + RCHO

=*

RCH=CHC$D

p

,

0

RCH-CHCHO

which are useful in the synthesis of unsaturated aldehydes, ketones, and acids, have been prepared using the phosphonium salt (64).62

15

85

(64)

(65)

Among other interesting phosphoranes used successfully in olefin synthesis are (66) 63 and those derived from the salts (67),64(68),66 (69),66(70),67(71),68 and (72) together with analogues of (72) prepared using other d i e n e ~ . ~ ~ QCHZCONPJ

0 (66) as 64

6a

w O0

, / CH-PPh, CO,CHPh,

Ph3kH2C(:CH2)COR C1(67)

T. M. Cresp, M. V. Sargent, and P. Vogel, J.C.S. Perkin I, 1974, 37. G. R. Malone and A. I. Meyers, J. Org. Chem., 1974, 39, 623. B.P. 1 342 242 (Chem. Abs., 1974, 80, 120 975). M. I. Shevchuk, I. V. Megera, N. A. Burachenko, and A. V. Dombrovskii, Zhur. org. Khim., 1974, 10, 167. Z. Tozuka, T. Otsubo, Y. Sakata, and S. Misumi, Mem. Inst. Sci. Ind. Res., Osaka Unia., 1973, 30, 83 (Chem. Abs., 1974,79, 66092). Jap. P. 73 08 108 (Chem. A h . , 1973,79,42 363). S. 0. de Silva and V. Snieckus, Canad. J. Chem., 1974, 52, 1294. E. C. Taylor and T. Kobayashi, J . Org. Chem., 1973, 38,2817. R. A. Ruden and R. Bonjouklian, Tetrahedron Letters, 1974, 2095.

174

Organophosphorus Chemistry + Ph,PCH,CH=CMeC-CH

(68)

Br'

+ Ph,P(CH,CH=CMeCH,),H

X-

(69)

The stilbene obtained from the salt (73) and the aldehyde (74) in methanol was predominantly trans whereas it was predominantly cis when the reaction was carried out in DMF.'O

Natural Products.-Details have appeared of the oxidation of axerophthylidenetriphenylphosphorane(75) to give @-carotene.71 Whereas oxygenation of the phosphorane in EtOT gave ditritio-bcarotene, showing that protonation

+ EtOH (75)

of (75) is more rapid than reaction with oxygen, treatment of the phosphonium periodate with ethoxide in EtOT gave p-carotene containing very little tritium. The phosphorane (75) must be oxidized by periodate ion faster than it is protonated by ethanol. 7O

I '

T. M. Cresp, R. G. F. Giles, and M. V. Sargent, J.C.S. Chem. Comm., 1974, 11. H. J. Bestmann, 0. Kratzer, R. Armsen, and E. Maekawa, Annalen, 1973, 760.

175

Ylides and Related Compounds

Aleuriaxanthinacetate(77) has been synthesized as shown, via the salt (76).7a A full account has appeared of the synthesis of &carotene and of optically

H

OAc

(77) 93%

inactive yy-carotene. 73 Among other syntheses of carotenoids using ylides are those of 7,8-didehydroi~orenieratene,~~ 7,8-dideh~drorenieratene,~* and a range of deuteriated ~arotenoids,~~ including 11,ll '-dideuterio-&-caroteneand [19,19'-2HJ#karotene. A range of polyenes has been prepared from crocetin dialdehydeand various benzylidenephosphoranes.76 Among labelled compounds synthesized using ylides are [2-14C]abscisic methyl tran~-[lO-~Qetinoate,~~ and trans[10-14Cjretinol.78 Details have appeared of the use of the ylide Bu,P:CHCO(CH2),CH3 in prostaglandin synihesis7Band of the synthesis of ectocarpen and related cycloheptadienes.aO Among other syntheses involving the use of ylides in key steps are those of acyclic analogues of trisporic acids,s1urushio1,82a sesquiH. K j ~ s e nand S . Liaaen-Jensen, Acta Chem. Scand., 1973,27,2495.

A. G . Andrewes and S . Liaaen-Jensen, Actu Chem. Scand., 1973,27, 1401. 74

7e

'?

O0

*I

T. Ike, J. Inanaga, A. Nakano, N. Okukado, and M. Yamaguchi, Bull. Chem. SOC. Jupan, 1974,47,350. A. Eidem and S . Liaaen-Jensen, Actu Chem. Scand., 1974,B28,273; J. E.Johansen and S . Liaaen-Jensen, ibid., pp. 301, 349. T.Hamasaki, K. Chin, N. Okukado, and M. Yamaguchi, Bull. Chem. SOC.Japan, 1973, 46, 1553. H.Lehmann, H. Repke, D. Gross, and H. R,Schuette, 2.Chem., 1973,13,255. J. D. Bu'Lock, S. A. Quarrie, and D. A. Taylor, J . Labelled Compounds, 1973,9,311. N.Finch, L. D. Vecchia, J. J. Fitt, R. Stephana, and I. Vlattas, J. Org. Chem., 1973,38, 4412. L. Jaenicke, T. Akintobi, and F.4. Marner, Annalen, 1973, 1252. L. N.Polyachenko, L. P. Davydova, V. V. Mishchenko, and G. I. Samokhvalov,J. Gen. Chem. (U.S.S.R.), 1973,43,409. M. Sato, Yukagaku, 1973,22, 349 (Chem. Abs., 1973,79,136 684).

Organophosphorus Chemistry

176

terpene from Elviva bijora DC.,83model compounds, e.g. (78), used in the identification of pigments from Wallemiu ~ e b i , ~freelingyne * (79),86 and a number of insect sex-attractants, e.g. (80).86 QCHO

+ Ph,P=CMeCHO

1400c*

wcHo I \ H

H

65% 6:4

(79) CH,CH~=CHCH,CH2h’h3 Br-

K

H M ~ CH,CH=CHCH,CH=PPh,

~~cHl~80a. CH,CH&HCH2CH’CH(CH3,OAc (80) 40%

Further examples have appeared of the reactions of protected aldehydo- and keto-sugars with simple ylides in conventional olefin ~ y n t h e s e s . ~ ~ Macrocyclic Compounds.-Further examples have appeared of two general approaches to the synthesis of annulenes. Ylides have been used for the

** F. Bohlmann and D. Korning, Chem. Ber., 1974,107, 84

O1

0’

1777.

Y. Badar, W. J. S. Lockley, T. P. Toube, B. C. L. Weedon, and L. R. G. Valadon, J.C.S. Perkin I, 1973, 1416. D. W. Knight and G. Pattenden, J.C.S. Chem. Comm., 1974, 188. H. J. Bestmann, 0. Vostrowsky, and A. Plenchette, Tetrahedron Letters, 1973, 779; H. J. Bestmann and 0. Vostrowsky, ibid., 1974, 207. J. M. J. Tronchet, C. Cottet, B. Gentile, E. Mihaly, and J.-B. Zumwald, Helu. Chim. A d a , 1973, 56, 1802; J. M. J. Tronchet, J. M. Bourgeois, and D. Schwarzenbach, Carbohydrate Res., 1973,28, 129; J. M. J. Tronchet and D. Schwarzenbach, ibid., 1973, 30, 395.

Ylides and Related Compounds

177

construction of aw-diacetylenes, e.g. (81), which have then been oxidatively cyclized,88whereas conventional bis-ylide cyclizations have been used in the synthesis of oxygen-bridged 1191- and [21]-annulenes, e.g. (82).89

(81) 30%

0-0-0

Ph,PCH,

(82) 12%

Full accounts have been given of the syntheses of heteroatom-bridged and of the reactions [17]annulenesO0 and of thia-[l7]- and -[21]-ann~lenes,@~ between the dialdehyde (83) and the bis-ylide (84), in which the thiopyran (85) was formed as well as the expected t h i ~ n i n s . ~ ~ P. J. Beeby, R. T. Weavers, and F. Sondheimer, Angew. Chem. Internat. Edn., 1974,13, 138; R. T. Weavers and F. Sondheimer, ibid., p. 141;J. M. Brown and F. Sondheimer, ibid., p. 337. T. M. Cresp and M. V. Sargent, J.C.S. Chem. Comm., 1974, 101. n o T. M. Cresp and M. V. Sargent, J.C.S. Perkin I , 1973, 2961. T. M. Cresp and M. V. Sargent, J.C.S. Perkin I, 1973, 1786. ** P. J. Garratt, A. B. Holmes, F. Sondheimer, and K. P. C. Vollhardt, J.C.S. Perkin I, 1973, 2253.

178

Organophosphorus Chemistry

+

+

(83)

4 Selected Applications of Phosphonate Carbanions

The Homer synthesis of olefins using phosphonate carbanions has been reviewed.gsSeveral careful investigationsg4of the mechanism of the Homer reaction have identified the effects of changing phosphonate, solvent, tem-

fl

R'

0 R3

R2

+ (EtO),P(0)CH,C0,R4

$:;+ !

R'

)4

R2

COMe

0 R3

(86)

CMe =CHC0,R4

53-9276 (MeO),P(O)CHRCHO

(87) RCOCH,OH + (EtO),P(O)CHCO,Et

(88)

-

0

J. Boutagy and R. Thomas, Chem. Rev., 1974, 74, 87. B. Deschamps, G. Lefebvre, A. Redjel, and J. Seyden-Penne,ibid., p. 2437; A. Redjel and J. Seyden-Penne, Tetrahedron Letters, 1974, 1733.

'' T. Bottin-Strzalko, Tetrahedron, 1973,29,4199;

Ylides and Related Compounds

179

perature, and the cation associated with the base on the relative rates of the various steps leading to isomeric olefins. Among carbonyl compounds used in olefin syntheses were (86),96 (8nYa6 and steroidal a-hydroxy-ketones (88) leading to cardenolide~.~~

fJ)fj

CH*P(O)(OEt)*

(90) (PhCH,O),P(O)CH,CO,H

X = OorS

2d2NLi THF

*

(PhCH,O),P(O)~HCO,Li

-80°C

(91)

R,C =CHC0,H C&CP(O)(OEt),

;iy

f-

LiCl,CP(O)(OEt),

RzCo:

RZC =CCI2

-80°C

(92)

Among phosphonates used in o l e h syntheses were (89) and (90),98the acid (91),99(92) and (93),lo0(94),62and (95),lo1Details have appeared of the use of *6

L. S. Stanishevskii,I. G. Tishchenko, V. I. Tyvorskii, and T. I. Prikota, Zhur. org. Khim., 1973, 9, 1369.

J.-L. Kraus and G. Sturtz, Bull. SOC.chim. France, 1974, 943. @' W. Kreiser, H.-U. Warnecke, and G. Neef, Annalen, 1973, 2071. A. Yamaguchi, T. Inada, and M. Okazaki, Nippon Kagaku Kaishi, 1973, 991 (Chem. Abs., 1973, 79,42 399). G. A. Koppel and M. D. Kinnick, Tetrahedron Letters, 1973, 711. l o oD. Seyferth and R. S. Marmor, J. Organornetallic Chem., 1973, 59, 237. lol M. Mikolajczyk and A. Zatorski, Synthesis, 1973, 669. 7

180

Organophosphorus Chemistry

the phosphonates (EtO),P(O)CHRNC lo2 and (EtO),P(O)CH,iMeR.lo8 Thiazines (97), intermediates in total syntheses of p-lactam antibiotics, were (EtO),P(O)CH(CO,R')NHCHS

+

RZCOCH,CI

A

3K,C03

1.1K2C03

C0,R'

(97)

(96)

obtained lo4by intramolecular olefination in the phosphonates (96). y-Alkylation of the dianions (98) has been used in the synthesis of (k )-ar-turmeronelo6 and of cyclohexenones, as shown in Scheme 9.1°a (MeO),P(O~HCOCH,R

A

(MeO),P(OEHC&HR (98)

(MeO),P(0)CH,CoCHRCH2CH2COMe

(MeO),P(0)CH2COCHRCH2CH=CClMe

R 0 Reagents: i, BuLi; ii, ClCH,CH=CClMe; ifi, W-H,O; iv, NaH-DME.

Scheme 9

The a-lithiophosphonate(99) is an excellent reagent for the half-reduction of gem-dibromocyclopropanes.lo U. Schollkopf, R. Schroder, and D. Stafforst, Annalen, 1974,44. K. Kando, Y. Liu, and D. Tunemoto, J.C.S. Perkin 1, 1974, 1279. R. W. Ratcliffe and B. G. Christensen, Tetrahedron LRtters, 1973, 4645, 4649, 4653. * 0 6 P. A. Grieco and R. S. Finkelhor, J. Org. Chem., 1973,38, 2909. l o ( P. A. Grieco and C. S. Pogonowski, Synthesis, 1973, 425. lo7 K. Oshima, T. Shirafuji, H. Yamamoto, and H. Nozaki, Bull. Chem. SOC. Japan, 1973,

lo' lo'

46, 1233.

Ylides and Related Compounds

+Br,

181

+ (EtO),P(O)CH,Li --+ (99)

HH Br

For ylide aspects of iminophosphoranes see Chapter 10.

I0 Phosphazenes BY

R. KEAT

1 Introduction An overall decrease in the number of publications on this topic is apparent, although the volume of patent literature is still increasing. Notable developments include the synthesis of a monophosphazene, (Me,Si),NP= NSiMe3, containing tervalent phosphorus and of a three-co-ordinated quinquevalent phosphorus compound (Me3Si)zNP(=NSiMe3),, and the incorporation of a phosphazene unit in a four-membered ring.4 A comprehensive survey of the synthesis and properties of cyclophosphazenes has appeared (already somewhat dated), and the importance of phosphazenes in the inorganic polymer field has been emphasized.6 2s

2 Synthesis of Acyclic Phosphazenes From Arnides and Phosphorus(v) Halides.-The Kirsanov reaction has been used to advantage in the synthesis of certain P-aryl-phosphazenes:

-- HCI

Cl,PC,I~FCl, + PhN+H, C1-

+

PhN=PCI,C,H,P(CIz)=NPh

Further phenylation can be accomplished by reaction with phenylmagnesium bromide to give products only previously obtained by the potentially hazardous azide route. Sulphamic acid also reacts with phenylchlorophosphoranesin a similar way :* H,NSO,OH

-t

PhnPCl,-,

-HCl

*

Ph,PCl,

-n

P=NSO,Cl

(n = 1,2, or 3),

E. Niecke and W. Flick, Angew. Chem. Internat. Edn., 1973, 12, 585. 0. J. Scherer and N. Kuhn, Chem. Ber., 1974,107,2123. a E. Niecke and W. Flick, Angew. Chem. IntGrnat. Edn., 1974, 13, 134. V. P. Kukhar’, T. N. Kasheva, and E. S. Kozlov, J . Gen. Chem. (U.S.S.R.),1973, 43, 741. 6 R. Keat and R. A. Shaw, in ‘Organic Phosphorus Chemistry’, ed. G . M. Kosolapoff and L. Maier, John Wiley, New York, 1973, Vol. 6, p. 883. a H. R. Allcock, Chem. in Britain, 1974, 10, 118; Scientific American, 1974, 230, 66. V. V. Kireev, V. V. Korshak, M. A. Eryan, and R. M. Minas’yan, J. Gen. Chem. (U.S.S.R.), 1973, 43, 430. a D. E. Arrington, Synth. Inorg. Metal-org. Chem., 1974, 4, 107.

*

182

183

Phosphnzenes

although for n = 2 the phosphazene was difficultto purify. The reactions of amides of the type RP(O)(OAlk)NH, with chlorophosphoranes have been the subject of an extensive study,Qparticularly to determine which of the two possible isomeric phosphazenes is formed. For example, of the products formulated as RONP2C14,structures (1) or (2) are possible. lH and 31Pn.m.r. spectroscopy showed that when R = Me the isomer present is (l), but when R = CCI, the preferred isomer is (2) (see also ref. 30).

The mechanism of the reaction of the diphosphinylamide [CI,P(O)],NH with phosphorus pentachloride has been studied,1° with the latter reagent labelled with 32P[marked with an asterisk in (3) and (4)]. A probable intermediate is (3), rather than (4), since radioactive POCI, is eliminated, leaving

the monophosphazene Cl,P=NP(O)CI,. Full details l1 of the preparation of cyclodiphosphazenes (5), which may be considered as dimeric phosphazenes,

Rz ( 5 ) R' = Foraryl;

R2 = Me, Et, or Ph from fluorophosphoranes and disilazanes have been published. The only monomeric phosphazene obtained in this way was MeN=PFPh,, whose crystal structure had previously been reported. * V. A. Shokol, G. A. Golik, Yu. N. Levchuk, Yu. P. Egorov, and G. I. Derkach, J. Gen. Chem. (U.S.S.R.),1973, 43, 266. lo

L. Riesel, M. Mauck, and E. Herrmann, 2. anorg. Chem., 1974,405, 109. R. Schmutzler, J.C.S. Dalton, 1973,2687.

Organophosphorus Chemistry

184

From h i d e s and Phosphorus(m) Compounds.-The azide synthesis of phosphazenes has been used to obtain 2v a novel trico-ordinate quinquevalent phosphorus compound, of the general type often postulated as an intermediate in nucleophilic displacements at phosphorus(v) : R,NP=NR

*

+ 2RN3

R,NP(=NR),N,R

(refs. 2 and 3) /-RN3

=% R2NP(=NR)2

(R,N),PN, (ref. 2)

(R = SiMe,)

As might be anticipated, the phosphorus atom is very electrophilic, so that rapid reactions occur with water and with alcohol^,^ e.g. R,NP(==-NR),

+ MeOH

-

(R,N)(MeO)(RNH)P=NR

Interesting products have also been obtained l2 from the reactions of phenyl a i d e with the 'birdcage'-type phosphorus(m) compounds P4(NMe)6 and I?&,. The former substrate gave P,(Nhfe),n(=NPh) [n = 1 or 4, e.g. structure (611, and products with n = 2 or 3 were identified by slP n.m.r. The NPh

II

(6)

relative concentrations of these four derivatives were estimated and used to calculate their relative rates of formation, which steadily decreased with increasing values of n. Only P,O,(=NPh) could be identified from a similar reaction with P406,and no reaction occurred with P4or P4S3.The cage aminophosphine (7) may be oxidized by phenyl azide and diphenylphosphinyl azide in a similar manner.13 When R = Ph,P(O), two sets of 31P signals were observed, and tentatively attributed to the presence of geometrical isomers. It :P(NMeNMe),P + 2RN3

la

+

RN=P(NMeNMe),P=NR

M. Bermann and J. R. Van Wazer, Inorg. Chem., 1973,12,2186. M. Bermann and J. R. Van Wazer, Inorg. Chem., 1974,13, 737.

f

2N2

185

Phosphazenes

is surprising that the 31Pspectrum did not constitute an example of an AA’BB’ spin system. The azide-induced oxidation of tervalent phosphorus incorporated in sixmembered rings (9) is readily accomplished. Phosphazenyl-derivativesof penicillins (11) have also been obtained l6 in this way. Me,Si’/ I

Y

M ~ , ~ ~ Me,qi’’\!jiMe, ~ ,

‘SiMe, I

Meh, ,hMe ,p.

Mek,

,NMe

/p\

Me

Me (9)

NSiMe,

(10)

(X = 0,ref. 14 X = NMe, ref.15)

Other Methods.-The stabilizing influence of the trimethylsilyl group has been nicely demonstrated l, in the synthesis of the first phosph(m)azane: KNPF, + LiNR,

--+

-t LiF

R2NP=NR

+ RF

(R = MSSi)

The same product has since been obtained2 by a somewhat simpler route: R,NLi

+ PX,

-2Lix :

(R,N),PX

-Rx

* RJW=“P

(R = Me,Si; X = Cl or Br) This phosphazene is characterized by fairIy ready reactions with nucleophiles, e.g.

H &NP=NR

+ HOR

I I OR

R,NP=NR

and by its very low-field 31Pchemical shift of 6 = 325 p.p.m., relative to phosphoric acid. The reaction of hexamethyldisilazane with chloro-phosphites provides a l4

l6 la

l7

U. Wannagat, K.-P. Giesen, and H. H. Falius, Monarsh., 1973, 104, 1444. H. H. Falius, K.-P. Giesen, and U. Wannagat, 2. anorg. Chem., 1973, 402, 139. J. P. Clayton and R. Hubbard, Ger. Offen. 2 335 721 (Chem. Abs., 1974,80, 108 512j). H. Binder and R. Fischer, Chem. Ber., 1974, 107, 205.

186

Organophosphorus Chemistry

novel route to certain phosphazenes, since it involves a tautomerization step: (RO),PCI + (Me,Si),NH

+ (RO),PNHSiMe,

+ (RO),HP=NSiMe,

(R = Me or Et) The synthesis of phosphmnes by the reactions of nitriles with chlorophosphoranes continues to receive attention. Thus methanecarbonitrile gives N-vinylphosphazenes,ls whose structures were assigned by 3sCI n.q.r. measurements: (NC),CNa + Ph,pc1,-.

_+

Ph,Cl,-, P=NC(Cl)=C(CN),

(n = 0, 1, or 3) All the chlorine atoms in these derivatives can be replaced by anilino-groups, and hydrolysis gives the parent primary amine, e.g.

+

Ph,PO

Ph,P=NC(Cl)=C(CN),

H,NC(Cl)==X(CN),

It was reported last year that tricyclic structures are obtained when N-cyanoallcylphosphazenesClsP=NCAlk2CN are treated with hydrogen chloride. It is now shown lothat replacement of one chlorine atom by a phenyl group results in the same type of product (12), but with two phenyl groups the acyclic

(12)

phosphazene ClPh2P= N - Alk2CN,which is unreactive to hydrogen chloride. However, phosphorus pentachloride, in the presence of hydrogen chloride, reacts with aromatic nitriles with no hydrogen atom on the a-carbon to the CN group, to give imine salts;20these salts are readily converted into phosphoryl compounds on reaction with sulphur dioxide, e.g. PhCN + PC1, + HCl --+ [PhC(Cl)=NPCl,N=C(Cl)Ph]' PC&

PhC(C1) =NPClN=C(CI)Ph

II

0

+ Pocl, + SOCl, Is

V. P. Kukhar', N. G. Pavlenko, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.), 1973,43, 1883.

I. M. Kosinskaya, A. M. Pinchuk, V. I. Shevchenko, and G. K. Bespalko, J. Gen. Chem.

(U.S.S.R.),1973, 43, 1890. *O

E. Fluck and F. Horn, Phosphorus, 1973,3, 59.

Phosphazenes

187

More examples of phosphazene synthesis by the reaction of carbon tetrachloride with primary amine derivatives of phosphines have appeared: Bu'RPNHNMe,

+

Cct

-CHC,,

Bu'RCIP=NNMe,

(R = Me or But) (ref. 21)

On standing at room temperature for some time, the phosphazene ButMeClP=NNMe2gives a polymer formulated as

A similar reaction with carbon tetrachloride has been observeda2with Nsilylated amino-phosphines, but sublimation of the products gives the cyclodiphosphazanes (13) as a mixture of cis- and trans-isomers. The cyclodiphosphazane (13; R = Ph) could also be obtained by treatment of ButP(NHR)(NRSiMe,)

-:iic

ButCI(Me,SiNR)P=NR

p R

BU~(RN=)P, ,N\

, P(=NR)BU'

N R (13) R = Me or Ph

ButCl(PhNH)P=NPh with triethylamine. Compound (13; R = Me) was converted into the analogous dithio-derivative, [ButP(S)NMe],, on reaction with phenyl isothiocyanate. It was recently reported that chloramination of bis(diphenyIphosphin0)mines (Ph,P),NR results in the formation of salts in which a rearrangement of the R group occurs: (Ph,P),NR

Nha* [H,NPh,P-N-PPh,NHR]+

cf-

The same type of rearrangement product has now23been obtained with

a

wider variety of N-substituents, and the mass spectra of these derivativeshave been discussed at length. The presence of a four-memberedring has a marked effect24 on the conversion of phosphine oxides into phosphazenes by tosyl (Ts) isocyanate.Thus (14) 0. J. Scherer and W. Gick, 2. Naturforsch., 1974, 29b, 129. 0. J. Scherer, P. Klusmann, and N. Kuhn, Chem. Ber., 1974,107, 552. ** D. F. Clemens and W. E. Perkinson, Inorg. Chem., 1974,13, 333. '4 C. R. Hall and D. J. H. Smith, Tetrahedron Letters, 1974, 1693.

1'

*s

188

Organophosphorus Chemistry

is smoothly converted into (15) with retention of configuration, probably because of relief of steric strain in the five-co-ordinated intermediate, but acyclic phosphine oxides R1R2R8P=0 are converted into R1R2R3P=NTs much more slowly, and with racemization at phosphorus. Further studies 26 of the reactions of quinones with phosphorus(rrr) amides, which give monophosphazenes (16), have been reported. A new synthesisas of (RO),P=Nth

-

(RO)$”HPh + O

a

e

~

O

H

(16)

monophosphazenes involves the reaction of phosphorus(m) amides, or of phosphites, with hexafluoroacetone-azine: + PR,

(CFd,C =NN=C(CF,),

-+

R3P=NC(CF,),N=

C(CF,),

(R included OAlk, NMe,, and Ph)

3 Properties of Acyclic Phosphazenes Halogeno-derivatives.-Anhydrous formic acid generally converts chlorophosphazenes into phosphinyl compounds, and the reaction with CI,P= NP(0)C12 is no exception:27 Cl,P=NP(O)Cl,

+ HC0,H +

Cl,P(O)NHP(O)Cl, + CO + HCl

A surprising feature of this product is that it does not readily eliminate hydrogen chloride (see also ref. lo), and can be converted into the N-methyl analogue on reaction with diazomethane. These results may be contrasted with those observed as for related compounds with P-alkyl substituents: AlkClRP=NP(O)Cl,

+

HCO,H

*

AlkClRP=NP(O)Cl(OH)

+ HC1 + CO

(R = C1 or OAr) A. N. Pudovick, 8. S. Batyeva, V. D. Nesterenko, and N. P. Anoshina, J. Gen. Chem. (U.S.S.R.),1973, 43, 29. K. Burger, W. Thenn, J. Fehn, A. Gieren, and P. Narayanan, Chem. Ber., 1974, 107, 1526. L. Riesel, H. H. PBtzmann, and H.-P. Bartich, 2.anorg. Chem., 1974, 404, 219. V. A. Shokol, G. A. Golik, Yu. N. Levchuk, Yu. P. Egorov, and G. I. Derkach, J. Gen. Chem. (U.S.S.R.), 1973, 43, 745.

189

Phosphazenes

Acidolysis can, however, be re-directed to the phosphazenyl-phosphorusatom when Alk is CHCI, or CCI,. The i.r. spectra of CI,P=NP(O)CI, and its l5N-1abelledanalogue have been and compared with the spectra of the [C13P~N9C13]-anion. * T I n.q.r. spectroscopy played an important ro1e30 in enabling isomers (17)

(R' = (3, R2 = Me; R' = OPh, R2 = CH2CI) and (18) to be distinguished (see also ref. 9). Both derivatives have structure (17) in the solid state. 36Cln.q.r. data have also been reported31for the dimeric phosphazene (C13PNMe)2. The N-chloroethylphosphazene CC13CC12N=PCls generally undergoes reactions with aromatic amines at both phosphorus and a-carbon atoms:3a CCl,CCI,N =PCl,

ArNH,

cc1,c/

N=P(NHAr),

\NAr

However, aromatic amine hydrochlorides and weakly basic aromatic amines effect selective reactions at the a-carbon atom to give derivatives of the type CC13C(=NAr)N= PCI,. Products of closely related structure were also obtained 33 on reaction with NN-dichloro-amines: RCCI,N=PCI,

+

Cl,NSO,Ar

-

RC(=NSO,Ar)N=PCl,

+ C1,

The hydrolysis of the acyclic chlorophosphazenes C14P(N=PCla3CI (obtained from N3P3Cls and PCIJ occurs faster at terminal than at the bridging phosphorus atoms. Further hydrolysis gives (HO),P(O)[NHP(O)(OH)],OH, and finally ammonium phosphate. Alkyl and Aryl Derivatives.-Potassium a i d e has been showna6to cleave benzyl groups from phosphorus in liquid ammonia at 120 "C: (PhCH2),P=NH I9

*l 8a

aa

+ 4KNH2 + K,[N=P(NH),],%NH,

+

3PhMe + %NH3

G. G. Dyadusha, E. S. Kozlov, and D. P. Khomenko, Teor. i eksp. Khim., 1973,9,535 (Chem. Abs., 1973,79, 145 572d). A. D. Gordeev, I. A. Kyuntsel', G.A. Golik, andV. A. Shokol, J. Gen. Chem. (U.S.S.R.), 1973, 43, 7. A. D. Gordeev, 8.S. Kozlov, and G. B. Soifer, J. Gen. Chem. (U.S.S.R.),1973,43,878. V. P. Kukhar', T. N. Kasheva, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.),1973,43,

18. V. P. Kukhar', M. V. Shevchenko, and A. M. Pinchuk, J. Gen. Chem. (U.S.S.R.),1973, 43, 1632. M. Kajiwara, H.Saito, and T. Saito, Nippon Kagaku Kaishi, 1973, 1432 (Chem. Abs., 1973,79,126 889w). B. Ross, 2. Naturfursch., 1973,28b. 359.

190

Organophosphorus Chemistry

The resulting pyrophoric potassium salt is of interest since it contains an azaanalogue of the phosphate anion. Further, this salt may be converted into a pyrophosphate analogue, formulated as K,[(HN),(N=)PNHP( =N)(NH),], in liquid ammonia. The cleavage of the Si -N bond in N-silylphosphazenes generally provides a versatile means of changing the N-substituents. However, reactions with chloro-phosphines are more complex in that a rapid quaternization step may occur, e.g. Me,P=NSiMe,

f

2Me2PC1

+

Me,P=NPMe,PMe,

C1-

+

Me,SiCl

Many new examples of these salts have now been reported,36including cases where quaternization was accomplished by chloro-arsines to give salts of the

+

type R3P=NPR2AsR2C1-. Si-N bond cleavage can also be effected3' by germanium chlorides and bromides to give monomeric phosphazenes, e.g. Me,P =NGeMeCI,, covalent dimers (19), and formally ionic dimers (20). Adducts formulated as C1,

Me,P=N

/% N-PMe, ' G e l

2R3P=NSiMe,MezGeIz were obtained with the only germanium iodide investigated, Me,GeI,. The reactions of the N-silylphosphazene Ph,MeP= NSiMe, with acid anhydrides or alkyl isocyanates all occur 38 with Si-N bond cleavage, e.g. Ph,MeP=NSiMe,

+ (MeCO),O

Ph,MeP=NSiMe,

+ MeNCO

-

Ph,MeP=NCOMe

+ MeCOOSiMe,

Ph,MeP=NCONMeSiMe,

By contrast, phenyl isocyanate and isothiocyanate and carbon disulphide led to addition4imination reactions of the Wittig type. The isocyanate reaction in particular gave a complex mixture of products, with ring-closure in the probable intermediate (21) occurring by P-N rather than P - 0 bond formation. Ph2PMe, + /Me,

I

W. Wolfsberger, 2.Naturforsch., 1974, 29b, 35. W. Wolfsberger and W. Pickel, J. OrganomefallicChem., 1973, 54, C8. IS. Itoh, M. Okamura, and Y . Ishi, J. Organornetallic Chem., 1974, 65, 327.

191

Phosphazenes

A large number of derivatives of the N-sulphuryl-phosphazene Ph3P=NS0&I have been obtained 39 from reactions with water, alcohols, amines, and sodium azide. Several potential routes to phosphazenyl-mercury compounds have been exarnined,'O but only the transamination reaction : MeHgN(SiMe,),

+

HN=P(NMe,),

--+

MeHgN=P(NMe,),

+ HN(SiMe,),

was found to give satisfactory yields. The physical properties of the monophosphazenes have attracted considerable attention recently. The vibrational spectra of Me,P=NMe and its N-deuteriomethyl derivative are interpretable 41 in terms of Cs symmetry, consistent with a non-linear P=N-C group. It is also interesting to note that the barrier to rotation about the P = N bond is less than 8 kcal mo1-I. The photoelectron spectra of Me,P= NH, Me,P= NSiMe3, and Me,P= NSiMe,SiMe,CH=PMe, have been compared4awith the spectra obtained for other phosphorus ylides. The electronic spectra of N,P-arylphosphazenes Ar,P=NAr are still the subject of intensive 4 Synthesis of Cyclic Phosphazenes The first synthesis of a phosphazene that forms part of a four-membered ring has been accomplished:

Some of the reactions of this novel ring compound are given in Scheme 1. It is to be anticipated that unusual chemical reactivity might be conferred by the presence of a small ring system, but the only comment to this effect concerns its relatively slow reaction with sulphur dioxide and hydrogen chloride. Its i.r. and 36CIn.q.r. spectra were also reported. Examples of phosphazenes which form part of a five-membered ring have

*' A. S. Shtepanek, V. A. Zasorina, and A. V. Kirsanov, J. Gen. Chem. (U.S.S.R.),1973, 43, 21. 4o

41

44 46

J. Lorberth, J. Organometallic Chem., 1974, 71, 159. J. Bragin, S. Chan, E. Mazzoia, and H. Goldwhite, J. Phys. Chem., 1973,77, 1506. K. A. Ostoja Starzewski, H. Tom Dieck, and H. Bock, J. Organometallic Chem., 1974, 65, 311. I. N. Zhmurova, V. P. Kukhar', A. A. Tukhar, and L. A. Zolotareva, J. Gen. Chern. (U.S.S.R.), 1973, 43, 79. I. N. Zhmurova and V. G. Yurchenko, J. Gen. Chem. (U.S.S.R.),1973, 43, 83. I. N. Zhmurova, R. I. Yurchenko, and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.), 1973,43, 1032.

40

47

I. N. Zhmurova, V. G. Yurchenko, R. I. Yurchenko, and T. I. Pavelko, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1772. T. G . adelmann and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.), 1973, 43, 554.

192

Organophosphorus Chemistry

c13cF-i

CC13CONH,

N-P(OAr),

CCI,C -N

II PC1, ll

N-

Reagents: i, NaOR; ii,.H,O; iii, EtOH; iv, HC0,H or HCl + SO,

Scheme 1

been known for some time, and a further instance is now provided:4s BdpYNSiMe,

Cl/ \NSiMe3 I

I Me

+

But\p/N-qiMez

ClSiMe,

I

ClSiMe,

t

Cl/

\N-SiMe, I

I

Me

A new route to a cyclic monophosphazene in a six-membered ring (22) involves the addition49of an isocyanate to a nitrilimine. Hydrolytic studies on these cyclophosphazeneswere also reported.

Further variations on the theme of the preparation of chlorocyclophosphazenes are describeds0 in a recent patent. This involved the formation of ammonium chloride in situ, before heating to effect the reaction with phosphorus pentachloride. Very neat preparations of alkyl- and aryl-cyclotri- and arylcyclotetra0. J. Scherer, W. Glassel, and R. Thdacker, J. Organometallic Chem., 1974, 70, 61.

** V. A. Galishev, V. N. Chistokletov, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1463. 6o

C. R. Bergeron and J. T. F. Kao, U.S.P. 3 780 162 (Chem. Abs., 1974,80, 85 3150.

Phosphazenes

193

phosphazenes have been devised,61 using the condensation of amides with phosphines in the presence of carbon tetrachloride (Scheme 2). [R’R2P(NH2),J+C1-+ (Ph,P),NH + CC14 + Et,N

‘u N-P R’R’f

Ph* \\

N

\

N=P

/

+ CHCl, + E&H

C1’

(R’and RZ = alkyl or Ph) + (Ph2P),NH + CCi4 + Et,N

R,(H,N)P=NP(=NH)R,

Scheme 2

5 Properties of Cyclic Phosphazenes

Halogeno- and Pseudohalogeno-derivatives.-Silver difluoride can be used fluorinate (23) selectively.

(23)

to

(24)

The chlorocyclophosphazenes (NPCl,), or are found s3 to be exceIlent reagents for the conversion of acyl halides into nitriles:

(R = Alkyl or aryl X = F, C1, or Br) R. Appel and G. Saleh, Chem. Ber., 1973, 106, 3455.

I1

H.H.Baalmann and H. C. Van de Grampel, Rec. Trav. chim., 1973.92, 1237. Ia J. C. Graham, Tetrahedron Letters, 1973,3825. 6a

Organophosphorus Chemistry

194

No solvent was used, and typically the reaction mixture was heated to 150200 "C (lower when R = Alkyl), when the phosphoryl halide distilled off, leaving the nitrile in 50-90% yield. The preparation of monoisocyanato- and monoisothiocyanato-derivatives. N3P3F5Zand N4P4F7Z(Z = NCO and NCS) from reactions of N3P3F5Cland N,P4F7Cl with ClS0,NCO and AgSCN, respectively, has been reported.64 These pseudohalogen derivatives undergo reactions with chlorine and dimethylamine: c1

XNCY -4- XN-CC1,

XNHCYNMe,

XNCY

(X = N,P,F, or N.,P,F,; Y = 0 or S)

Earlier correlations, relating the magnitude of the spin-spin coupling constant J E - N - ~to the properties of the phosphorus substituents in cyclotriphosphazenes, have been extended66to include a wider range of endo- and exo-cyclic substituents. When carbon replaces phosphorus in rings of the type (25), JZ-N-Eis reduced by a constant factor for a given substituent, and it was

I

R3 (25)

pointed out that this is paralleled by a reduction in the PNP bond angle. 31P n.m.r. data have been reported6* for N3P3F6,N3P3C16,and N4P4C18in the nematic phase, from which the respective molecular symmetries were deduced. The 31P shift anisotropy suggests that electron delocalization is most effective in N3P3F6.Dynamic nuclear polarization studies 5 7 of the lgFand 31Pnuclei in the series (NPF2)3-7show that scalar coupling between free radicals and 31P nuclei is less in the fluorocyclophosphazenes than in the chlorocyclophosphazenes. It was reported last year that 36CIn.q.r. frequenciesmay be related to P-Cl bond lengths in chlorocyclophosphazenes. This point has been re-stated,68 64 66 60

67

bn

H. W. Roesky and E. Janssen, 2.Naturforsch., 1974,29b, 174. K.Schumann and A. Schmidpeter, Phosphorus, 1973,3,51. N . Zumbulyadis and B. P. Dailey, J. Magn. Resonance, 1974, 13, 189. E. H.Poindexter, R. D. Bates, N . L. Paddock, and J. A. Potenza, J. Amer. Chem. SOC., 1973,95,1714. V. E. Belskii, V. A. Naumov, and I. A. Nuretdinov, Doklady Akad. Nauk, S.S.S.R., 1974,215, 355.

195

Phosphazenes

and it was also noted that these frequencies are related to the ClPCl bond angle. n.q.r. measurements have also been made69on compounds of the type (26). CND0/2 calculationsgoon N,P,F,, give a lower total energy when the

results of the most recent electron-diffractionstudy (see these Reports, Vol. 4) are used than do the results obtained in earlier work. Similar calculations were performed for N3P3CI,. Amino-derivatives.-Practical details of the preparation of N,P,CI,jNH, and geminal N3P3CI,(NH2)2have been published.61 The reactionsBa of the hydrazino-derivativeN3P3F6NHNH2 are given in Scheme 3. XNHNHCOMe

XNHNHX

\ XNHN=CHPh

1

XNHNH,

\

XNHN=CMe,

EtHC-N

/NHX

I I

/N-CHEt XNH

(X = NJ,F,) Reagents: i, MeCOCl; ii, N,P,F,Br; iii, EtCHO; iv, Me,CO; v, PhCHO

Scheme 3

The pentakisdimethylamino-derivative N3P3Cl(NMe2)5, only recently ~ Bbeen , isolated by detected in the dimethylaminolysisproducts of N ~ P ~ Chas g . l . ~and . ~ ~characterized as the fluoride N3P8F(NMea)5. Antimony trifluoride is a useful reagent for both the fluorination of dimethylaminochlorocyclotetraphosphazatetraenesB 4 and for the replacement of dimethylamino-groups E. A. Romanenko, Yu. P. Egorov, and P. P. Kornuta, Teor. i eksp. Khim., 1973,9,635 (Chem. Abs., 1974, 80, 42 654y). ' O J.-P. Faucher and J.-F. Labarre, J. Mol. Structure, 1973, 17, 159. G. R. Feistel, M. K. Feldt, R. L. Dieck, and T. Moeller, Inorg. Synth., 1973, 14, 23. @*H. W. Roesky and E. Janssen, 2.Nuturforsch., 1974, 29b, 177. 6 a P. Clare and D. B. Sowerby, J. Inorg. Nuclear Chem., 1974, 36, 729. ** D. Millington and D. B. Sowerby, J.C.S. Dalron, 1973, 2649.

Organophosphorus Chemistry

196

by fluorine atoms in the octakisdimethylamino-derivativeN4P4(NMe2)8. Thus a mixture of three isomeric non-geminal tetrachloro-derivatives N4P4C14(NMe2)4 were converted into a similar number of tetrafluorowas also converted derivatives (27)-(29). A pentachloride N4P4C15(NMe2)3

(30)

into (30). The replacement of dimethylamino-groups by fluorine atoms was observed in both cases, and this led to the formation of complex reaction mixtures, separable by g.1.c. The structures of these products were assigned on the basis of lH and lSFn.m.r. spectroscopy.The same techniqueswere applied 65 to the fluorination products of N4P4(NMe&, from which fourteen nongeminally substituted derivatives N4P4F,(NMe,)8-, [n = 1 ,2 (four isomers), 3 (three isomers), 4 (three isomers), or 5 (three isomers)]were obtained. Larger amounts of trans- than cis-isomers were generally obtained. Fluorination is believed to proceed by initial co-ordination of a phosphazene-ring nitrogen atom to SbF3, and evidence was obtained for an adduct of approximate composition N4P4(NMe&,4SbF,. The appearance of virtual coupling effects in the lH n.m.r. spectra of the two dimethylamino-derivatives N4P4C1,(NMe2), and N4P4C1z(NMe2)shas been usedBsfor structural assignments, which are in agreement with X-ray crystallographic studies (see also refs. 86, 115, and 116). A study of the Faraday effect of some dimethylamino-, isopropylamino-, and t-butylamino-derivatives of N,P,CI, shows that molecular magnetic rotations (of polarized light) increase with increasing degree of aminolysis. I6

67

D. Millington and D. B. Sowerby, J.C.S. Dalton, 1974, 1070. G. J. Bullen, P. E. Dann, V. B. Desai, R. A. Shaw, B. C. Smith, and M. Woods, Phosphorus, 1973, 3, 67. M. F. Bruniquel, J.-P. Faucher, J.-P. Labarre, M. Hasan, S. S. Krishnamurthy, R. A. Shaw, and M. Woods, Phosphorus, 1973, 3, 83.

197

Phosphazenes

The electrical conductivity of a series of amino-derivatives of N3P3C16is greater than that of N3P3Cl, itself.68 No more than two of the chlorine atoms in N3P,C16 can be replaced by triphenylphosphazenyl groups in reactions with Ph3P=NH,6s leading to a mono-derivative N3P3ClS(N=PPh,) and two non-geminal bis-derivatives N3P3C14(N=PPh,),. A number of dimethylamino-derivatives of N3PSc1,(N=PPh,) were prepared, and an unexpected result was that initial dimethylaminolysis occurs at the =PCl(N=PPh3) group to give a geminal product

(31). However, the reaction of N,P,Cl,NMe, with Ph,P=NH gave the nongeminal product (32). The tetramer N4P4C18also gave a mono- and two bistriphenylphosphazenylderivatives. Structureswere assigned on the basis of lH n.m.r. spectroscopy and basicity measurements. The tetrachloro-derivative N3P3Cl,(NC,HsO)(NC2H,), a product of the reaction of the monomorpholino-derivativeN,P,Cl,(NC,H,O) with aziridine, has a non-geminal structure.70 A novel cyclophosphazene-substitutedtin-nitrogen ring compound (33) has been identified 71 from the reaction:

N3P3F, (33)

Several investigations have been undertaken to assess the reactivity of the =PC12 group relative to that of other electrophiliccentres. The replacement of chlorine atoms in the cyclophosphazene(34) by primary and secondary amines occurs72in the order shown.

70

’*

T. Hayashi and H. Saito, Nippon Kagaku Kaishi, 1973, 2191 (Chem. Abs., 1974, 80, 41 930y). M. Biddlestone and R. A. Shaw, J.C.S. Dalton, 1973, 2740. L. E. Mukhina, A. A. Kropacheva, T. S. Safonova, and V. A. Chernov, U.S.S.R.P. 220 983 (Chem. Abs., 1973,79, 78 849j). H. W. Roesky and H. Wiezer, Chem. Ber., 1974, 107, 1153. V. I. Shevchenko, A. I. Kalenskaya, and P. P. Kornuta, J. Gen. Chem. (U.S.S.R.), 1973, 43, 13.

Organophosphorus Chemistry

198

The sulphur-containingheterocycles (38) both undergo preferential reactions at the phosphorus atom with primary and secondary amines (including silylamines). It is interesting to note that the monoamino-derivatives were obtained on reaction with ammonia, whereas only diamino-derivativescan be obtained from a similar reaction with N,P&& (cf. ref. 61). By contrast, (38; 0

0 NHR’R2

X = C1, ref. 7 3 X = F,ref. 74 X = CI) is preferentially fluorinated 73 at the sulphur atoms by AgF, to give (38; X = F). Alkoxy- and Aryloxy-derivatives.-The lH n.m.r. spectra of cyclotriphosphazatrienes with alkoxy-substituents, including the series N3P3C16-n(OBun)n (n = 1, 2, 3, or 6) have been d e ~ c r i b e d ,with ~ ~ particular regard to the appearance of ‘virtual coupling’ effects. Group refraction data have been tabulated 76 for chloroalkoxycyclotriphosphazatrienes with OCHzC2F6and OCH2C3F7substituents. In connection with studies of the relative reactivities of cyclotriphosphazenes, a large number of pentakisaryloxy-derivatives N,P,CI(OAr), have been

74

Is 7’

U. Klingebiel, T.-P. Lin, B. Buss, and 0. Glemser, Chem. Ber., 1973, 106, 2969. W. Heider, U. Klingebiel, T.-P. Lin, and 0. Glemser, Chem. Ber., 1974, 107, 592. T. P. Zeleneva, I. V. Antonov, and B. I. Stepanov, J . Gen. Chem. (U.S.S.R.), 1973, 43, 1000. V. V. Korol’ko, V. N. Sharov, V. N. Prons, and A. L. Klebanski, J. Gen. Chem. (U.S.S.R.), 1973, 43, 586.

199

Phosphazenes

prepared.77In some cases these derivatives have been a m m ~ n o l y s e dand , ~ ~the following sequence of reactions has been carried out: N,P,Cl(OAr),

5 N,P,(NH,)(OAr),

pc4 h

N,P,(N-PPCl,)(OAr),

N,P,[ N=P(OR),OH]

(OAr),

The 31Pn.m.r., u.v., and i.r. spectra of some of these derivatives were reported, and basicity measurements discussed. The major product from the ammonolysis of the non-geminal triphenoxy-derivative N,P,CI,(OPh), is N3P3CI(NH,),(OPh),. The triamino-derivative N,P,(NH,),(OPh), was only obtained in 5 % yield.79 The reactions of the alkoxycyclophosphazenes [NP(OCH,CF,)aJ,, with diphenyl ketone result in the formation of the acid (CF,CH,O),P(O)(OH) and organic imines.80, The cyclophosphazene N3P3C16(and N4P4C18)reacts with formamide and thioformamide to give metaphosphimic and metathiophosphimic acids, respectively.82These acids appear to be in tautomeric equilibrium, e.g.

/I

HX

\

XH

(X = 0 or S ) The thioalcoholysis of N4P,C18generally results 8 3 in the replacement of four chlorine atoms to give derivatives of probable structure (42), based on evidence

I. B. Telkova, V. V. Kireev, V. V. Korshak, A. A. Volodin, and A. A. Fomin, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1247. 78 A. A. Volodin, V. V. Kireev, V. V. Korshak, and A. A. Fomin, J. Gem Chem. (U.S.S.R.), 1973,43,2198. 7 s H. Schadow and H. Scheler, 2.Chem., 1973,13, 223. 8 0 R. A. Shaw and E. T. Mukmenev, Doklady Akad. Nauk S.S.S.R., 1973, 208, 379. 81 R. A. Shaw and E. T. Mukmenev, Khim. geterotsikl. Soedinenii, 1973, 945. ** B. Yanik and V. Zheshutko, J. Gen. Chem. (U.S.S.R.), 1973, 43, 273. A. P. Carroll, R. A. Shaw, and M. Woods, J.C.S. Dalton, 1973, 2736.

71

200

Organophosphorus Chemistry

from vibrational and 31Pn.m.r. spectroscopy. Further evidence for this assignment comes from a consideration of the IH n.m.r. spectra of the products of dimethylaminolysis of (42), namely N4P4(NMe2)4(SR)4 (see also ref. 86). A geminal chlorine-atom replacement pat tern was previously reported for thioalcoholysis reactions with N3P3C16,and the reaction pattern in both trimeric and tetrameric ring systems may be rationalized in terms of interactions between ‘hard’ and ‘soft’ acids and bases. Aryl Derivatives.-The lH n.m.r. spectra of the arylfluorocyclophosphazenes N,P,F6-nPhn [n = 1,2 (3 isomers), and 41 have been studied.84By deuteriation at the meta-position in the phenyl groups it was possible to measure ortho- andpara-proton shifts accurately, and hence to estimate the conjugative eIectron withdrawal by the cyclophosphazenering, using previous correlations on this topic. The electron withdrawal decreases with increasing degree of phenylation, and significant differences are observed between cis- and transisomers. The aluminium-chloride-catalysedFriedel-Crafts phenylation of chlorodimethylaminocyclotriphosphazatrienesN,P3Cl,-n [n = 1’2 (two isomers), and 3 (three isomers)] occurs more rapidly at EPClNMe, groups than at =PCI, groups,85an observation that may be rationalized in terms of the better + stabilization of the =PX ion when X = NMe2 than when X = C1. Triphenylmethane and diphenylmethane were minor by-products from these reactions, but these hydrocarbons were major by-products in the phenylation of non-geminal cis-N3P,Cl,(NMe,),. The appearance of ‘virtual coupling’ effects in the lH n.m.r. spectra of the two geminal isomers of N4P4(NMe2)4Ph4, (43) and (44),has enabled them to be

distinguished.86The lH n.m.r. spectrum of (43) shows a typical dimethylamino-proton doublet (by coupling to 31P),but that of (44)shows a doublet enclosing a ‘hump’ (virtual coupling effect). These assignments are confirmed by an X-ray study of the precursor of (43), i.e. N4P,C14Ph4(see Section 7). Octahedral chromium(m) chelate complexes CrL, (43, CrL,(acac), and

aa

C. W. Allen and A. J. White, Inorg. Chem., 1974, 13, 1220. S. Das, R. A. Shaw, and B. C. Smith, J.C.S. Dalton, 1973, 1883. M. Biddlestone, G. J. Bullen, P. E. Dam, S. S. Krishnamurthy, R. A. Shaw, and M Woods, Phosphorus, 1973, 3, 179.

Phosphazenes

CrL(acac), (acac = acetylacetonate) have been obtained Ph,P(O)NHP(O)Ph,.

201

from the ligand

6 Polymeric Phosphazenes

Two general reviews on this topic have been previously noted.g The polymerization of cyclic chlorophosphazenes, and the separation of chlorophosphazene oiigomers8 9 and their subsequent ammonolysis have been described. These ammonolysis products constitute a useful flameproofing agent for cellulose fibre.91 Amino-derivatives of oligomeric cyclic and linear phosphazenes have been usedaa in the preparation of a catalyst for the stereospecific polymerization of a-olefins. N,P,Cl, rings are cleaved by phenyl-lithium in diethyl ether solution to give oligomeric acyclic phosphazenes in which the terminal phosphorus atoms are phenylated. The remaining =PCla groups in the chain are easily aminolysed by dimethylamine. The flame-proofing of textiles by oligomeric n-propoxyphosphazenes has been further in~estigated,~~ and other alkoxypolyphosphazenes have been reported,95-100 with those containing fluoroalkoxy-groupscurable at room g8, or elevated lootemperatures. Polymeric phosphazenes containing aryloxy- or amino-groups are useful additives to high-pressure lubricating oils.1o1 The formation of siloxanes containing phosphazene rings has been J. P. King and B. P. Block, US. Nut. Tech. Inform. Service, A . D . Rep., 1971, No. 763 694 (Chem. Abs., 1973, 79, 121 364m). K. A. Reynard and S. H. Rose, Ger. Offen. 2 220 800 (Chem. Abs., 1973,78,98 2624. 8 D J. E. Hall and A. F. Halasa, Fr. Demande 2 159 493 (Chem. Abs., 1974, 80,4648s). s o E. Kobayashi, Y.Ono, and H. Sahara, Japan. Kokai 73 51 899 (Chem. A h . , 1974,80, 85 319k). T. Kadokura, M. Saito, and T. Miyagi, Japan. Kokai 72 45 636 (Chem. Abs., 1974,80, 28 405m). ** J. Rybicky, J. Mejzlik, and K. Dostal, Czech. P. 147 511 (Chem. Abs., 1973, 79, 147 020w). M. Biddlestone and R. A. Shaw, Phosphorus, 1973, 3, 95. *' B. R. Franko-Filipasic, E. F. Orwoll, and V. C. Patel, Ger. Offen. 2 306 510 (Chem. Abs., 1974, 80, 97 282f). s K V. V. Kireev, A. V. Lomonosov, D. I. Skorovarov, and E. A. Filippov, U.S.S.R.P. 385 980 (Chem. Abs., 1974,80,71 337c). ** E. Tsuchida, Japan. Kokai 73 05 721 (Chem. Abs., 1973,79, 19 39813). E. Tsuchida, Japan. Kokai 73 05 723 (Chem. Abs., 1973,79, 19 655v). S. H. Rose and K. A. Reynard, U.S.P. 3 702 833 (Chern. Abs., 1973,78, 98 764k). B o S. H. Rose and K. A. Reynard, S. African P. 71 07 092 (Chem. Abs., 1973,78,98 769r). l o o Horizons Research Inc., Fr. P. 2 157 217 (Chem. Abs., 1973, 79, 147 289r). Y.Ito and M. Kajiura, Japan. Kokai 72 48 483 (Chem. Abs., 1973,79, 147 946~). 87

Organophosphorus Chemistry

202

studied,lo8# lo3and much effort has been directed 104-10a to the production of phenol-based resins, whose heat- and flame-resistant properties are improved by the presence of cyclic and linear phosphazenes. Acids derived from the hydrolysis of polyalkylchlorophosphazenes make useful extraction agents for Cu2+,Zn2+, and Ca2+ions.11o 7 Molecular Structures of Phosphazenes Determined by X-Ray Difhction Methods Compound

PhsP =NSO2CaH4-p-Me

Ph

Comments As preliminary report (Vol. 4) Two exo P-N bond lengths of a prox. and equal length [1.578and 1.585(7) shorter than nearest endo P-N bond lengths [1.625(7)A]

11,

Ref.

111 112

[N3P3mMe8)6H+12 [M0601b2-1

As preliminary report (Vol. 5), spectroscopic properties also discussed

113

~~p(,)~

Host : guest ratio = 1 : 3 Benzene molecules tumbling within ‘channels’ formed by guest molecules

114

Centrosymmetric ‘chair’ conformation, approx. C2h symmetry. P-N (endo) 1.580and 1.558(2) A, P-N (exo) 1.618(4)A

115

(clathrating benzene) N24C16(NMe2)2 (2,4,4-trans-6,8,8 :4,6)

N. N. Kolmykova, V. V. Kireev, V. V. Korshak, I. M. Raigorodskii, and V. I. Gorokhov, Vysokomol. Suedinenii, 1973, 15, A, 2188 (Chem. Abs., 1974,80,48 618m). Ioa V. V. Kireev, I. M. Raigorodskii, and G. Telegin, Trudy Moskov. Khim. Tekhnol. Ins?., 1972, 197 (Chem. A h . , 1973,79, 19 484p). lo4 T. Maikuma, H. Kawamura, and M. Oota, Japan. Kokai 73 40 900 (Chem. A h . , 1974, 80,48 684e). IDS H. Kawamura and S. Ikeno, Japan. Kokai 73 08 267 (Chem. Abs., 1974,80,37 783k). l o 6 H. Kawamura and S. Ikeno, Japan. Kokai 73 08 269 (Chem. A h . , 1974, 80, 37 920c). K. Doi, H. Kawamura, and S. Ikeno, Japan. Kokai 73 08 268 (Chem. A h . , 1974, 80, 37 921d). I o 8 H. Sat0 and R. Yoshie, Japan. Kokai 72 47 877 (Chem. Abs., 1974,80,37 927k). l o BK. Nakamura and H. Yamaguchi, Japan. Kokai 73 08 600 (Chem. Abs., 1974, 80, 37 634n). A. N. Asabin, 0.P. Avramova, V. S. Shizhko, and M. D. Ivanovskii, Zzuest. V. U.Z., Tsuet. Met., 1973, 16, 25 (Chem. Abs., 1974, 80, 5925s). A. F. Cameron, N. J. Hair, and D. G. Morris, Acta Cryst., 1974, B30, 221. M. Biddlestone, G. J. Bullen, P. E. Dann, and R. A. Shaw, J.C.S. Chem. Comm., 1974, 56. 11* H. R. Allcock, E. C. Bissell, and E. T. Shawl, Inorg. Chem., 1973, 12, 2963. 114 H. R. Allcock and M. T. Stein, J. Amer. Chem. Soc., 1974, 96, 49. l16 G. J. Bullen and P. E. Dann, J.C.S. Dalton, 1973, 1453. lo*

203

Phosphuzenes N4P4Cl,O\TMe!J 8

(2-trans-6 :2,4,4,6,8,8)

116

11'

l*O

Centrosymmetric 'chair' conformation, approx. C 2 k symmetry. P-N (endo) 1.586 and 1.555(3) A, P-N (exo) 1.640-1.669(3) 8, Saddle-shaped ring close to D 2 h symmetry Co-ordination to W by exo- and endocyclic N. Preliminary report (Vol. 5) Ring nearly planar with five ring atoms within possible bonding distance. Poor quality crystals gave data of low accuracy Ring has unusual distorted 'tub' conformation. Extra methyl group bound to N as expected H bound to ring N in 1 and 5 positions, but not located accurately Centrosymmetric, with double tub conformation, P-N bonds of equal length, 1.567 A

116

86

117

118

119

120 121

G.J. Bullen and P. E. DaM, J.C.S. Dalton, 1974, 705. H. P. Calhoun, N. L. Paddock, and J. Trotter, J.C.S. Dalton, 1973, 2708. F. A. Cotton, G. A. Rusholme, and A. Shaver, J. Co-ordination Chem., 1973, 3, 99. H. P. Calhoun and J. Trotter, J.C.S. Dalton, 1974, 377. H. P. Calhoun and J. Trotter, J.C.S. Dalton, 1974, 382. M. W.Dougill and N. L. Paddock, J.C.S. Dalton, 1974, 1022.

11 Photochemical, Radical, and Deoxygenatio n Reactions BY R. S. DAVIDSON

1 Photochemical Reactions Irradiation of the phospholen (1) in alcoholic solutions containing xylene as a triplet sensitizer gives the isomeric phospholen (2) and the addition product (3).l The relative yields of (2) and (3) are dependent upon the alcohol used. Thus t-butyl alcohol, by comparison with methanol, favours product (2).

GMe

ROH-Xylene hv

~

P

fiMe \* P

Pr’OH hv

Ph/

oMe

ph’

\b

(4)

Although these reactions of the phospholen parallel the well-known photoreactions of cyclohexenes with alcohols,2a it is interesting to note that 1methylcyclopentene does not undergo such reactions but leads to products derived by radical processes.2b This has been attributed to cyclopentene having a very rigid structure and being unable to form a ‘twisted triplet’. It would therefore appear that in the case of the phospholen the phosphorus atom enables a greater degree of flexibility in the ring. By way of contrast to the phospholen (l), the phospholen oxide (4) gives reduction products on irradiation in hydrogen-donating solvents. A definitive study has been made of the photodecomposition of the ylide (5).3 It was shown that the relative yields of the two products (6) and (7) are l

a a

H. Tomioka and Y . Izawa, Tetrahedron Letters, 1973,5059. (a) J. A. Marshall, Accounts Chem. Res., 1969, 2, 33; (b) P. J. Kropp, J. Amer. Chem. SOC.,1969, 91, 5783. R. R. da Silva, V. G . Toscano, and R. G . Weiss, J.C.S. Chem. Comm., 1973, 567.

204

Photochemical, Radical, and Deoxygenation Reactions

205

dependent upon whether decomposition occurs from either the excited singlet or triplet state of (5). When triplet sensitizationconditions were employed, the relative yields of the products were the same as when triplet diazoacetophenone Ph,P: CHCOPh (5 1

+L

Me2S :CHCOPh

PhCOCH:

-5-7

-

PhCOMe

(8)

+

kCo

or the ylide (8) were decomposed in cyclohexene. This evidence conclusively demonstrates that the excited ylide ( 5 ) decomposes to give a carbene and triphenylphosphine. Full details have now been published of the products obtained on direct irradiation and triplet-sensitized photoreactions of (9).4

(9)

A most interesting observation is that, in the crystalline form, (10) exhibits tribol~minescence.~ Thus on grinding the crystals, or on plunging them into (Ph,P),C :

(10)

liquid nitrogen, light is emitted. The emission has been characterized as phosphorescence. Further photoreactions of diazomethylphosphonates, e.g. (1l), have been reported, and the products formed have been interpreted as being produced via

R' /OMe .P-OMe

hu

Benzene

\\D

R2&P(0Meh

It

= R'/ = Ph

R'

0

J

0

R'

E. W. Turnblom and T. J. Katz, J. Amer. Chem. SOC.,1973,95,4292.

J. I. Zink and W. C. Kaska, J. Amer. Chem. SOC.,1973,95,7510.

Organophosphorus Chemistry

206

an intermediate carbems If one of the R groups in (11) is a phenyl group, product formation appears to occur via intramolecular insertion of the carbene into the phenyl group to give (12). The cyclopropene (13) ring-opens to give a carbene on photolysis and reacts with diphenyldiazomethaneto give

(15)

the pyrazoline (14). Photolysis of this compound ultimately gives the bicyclo[l,l ,O]butane (15). Attempts have been made to record the absorption spectra of radicals produced by flash photolysis of several fluorophosphines and tetrafluorobiphosphine.' Well-resolved spectra were not obtained. Irradiation or thermolysis at 300 "Cof tetrafluorobiphosphinein the presence of ethylene leads to tetrafluoroethylenediphosphine. Presumably reaction involves homolysis of the P- P bond to give difluorophosphino radicals. Irradiation of biphosphine disulphides and dioxides in the presence of oxygen gives products derived by initial cleavage of the P-P bond.Q This hypothesis appears to be substantiated by the observation that (17) is formed on decomposition of (16) in

& Ph,PH + Ph,POMe II II

S

S

A. Hartmann, W. Welter, and M. Regitz, Tetrahedron Letters, 1974, 1825.

' E. G. Skolnik, R. J. Salesi, C. R. RUSS, and P. L. Goodfriend, J. Phys. Chem., 1973,77, 1126.

K. W. Morse and J. G. Morse, J. Amer. Chem. Soc., 1973, 95, 8469. * T. Emoto, R. Okazaki, and N. Inamoto, Bull. Chem. Soc. Japan, 1973,46, 898.

PhotochemicaI, Radical, and Deowygenation Reactions

207

the presence of AIBN. Irradiation of (16) in the presence of methanol gives (18) and (19). 2 Phosphinidene Oxides and Related Species The reaction of the relatively unstable phosphine oxide (20) with dimethyl acetylenedicarboxylate gives dimethyl naphthalene-2,3-dicarbo~yIate.~~ This

reaction presumably involves (21), which undergoes expulsion of phenylphosphinidene oxide with concomitant aromatization of the bicyclic system. Photolysis of the phospholen oxide (22)was shown to give initially phenylphosphinidene oxide by trapping this with alcohols.11 From the fact that the reaction proceeded less readily in t-butyl alcohol solution, it was proposed that the phosphinidene oxide can react with the diene (23) to regenerate (22).

A similar electrocyclic reaction of the oxide with a-diketones is well documented. This reaction, utilizing benzil, has in fact been recently used to trap phosphinidene oxides and sulphides generated by the action of such metals as magnesium and zinc on phosphonic and phosphonothioic dichlorides. l8 The adducts, e.g. (24), react with magnesium in the presence of magnesium

T. H. Chan and K. T. Nwe, Tetrahedron Letters, 1973, 4815. H. Tomioka, Y.Hirano, and Y. Izawa, Tetrahedron Letters, 1974, 1865. l a M. Yoshifuji, S. Nakayama, R. Okazaki, and N. Inamoto, J.C.S. Perkin I, 1973,2065. I * S. Nakayama, M. Yoshifuji, R. Okazaki, and N. Inamoto, J.C.S. Perkin I, 1973,2069.

lo

l1

208

Organophosphorus Chemistry

chloride to generate, amongst other products, diphenylacetylene.l3Quite high yields (63 %) of the acetylenewere realized. Phosphinidene oxides and sulphides have also been trapped by adduct formation with alkyl disulphides.12 3 Radical Reactions A review has recently been published on the subject ‘Phosphorus Radicals’.14 Once again e.s.r. spectroscopy has proved to be an invaluable tool for investigating the kinetics of reactions of phosphorus radicals. Thus the rate constants for the bimolecular reactions of several types of phosphorus radicals, e.g. phosphinyl, phosphonyl, and phosphoranyl radicals, with like species have been determined and shown to be of the same order as, or very close to, the diffusion-controlled limit. l6 These annihilation reactions presumably involve formation of a P- P-bonded dimer. An interesting observation recorded in the paper reporting this work was that t-butoxyl radicals react with (25) to give phosphinyl radicals. But0’ + (EtO),PP(OE t), --+

Bu‘O (Eto), @P(OEt),

Bu‘OP(OEt), + (EtO),P*

Other reported reactions involving phosphinyl radicals include the reaction

of dimethylphosphinelS and tetramethylbiphosphinel7 with tetrafiuoroethylene. The gas-phase reaction of dimethylphosphine with the olefin occurs quantitatively, and a free-radical chain mechanism was postulated. Detailed kinetic analysis of the reaction indicated that a rather unusual type of initiation reaction occurs, in which, it is thought, the olefin (26) reacts as a biradical. The dF,kF, + Me,PH

__f

dF,CHF,

+

Me,@

InitiationReaction

(26) Me,@ .+ CF2=CF2 Me,PCF,kF, + Me,PH

-+ Me2PCF,eF,

--+ Me,PCF,CHF, + Me,@

biphosphine also reacts with the olefin in the gas phase but in this case the initiation reaction is the homolytic cleavage of the biph0~phine.l~ The reactions of diethoxyphosphonyl radicals with a variety of olefins have been reported. For example, with limonene they react to give (27) and (28).le l4

W. G. Bentrude in ‘Free Radicals’, ed. J. K. Kochi, Wiley, New York, 1973, Vol. 2,

p. 595. D. Griller, B. P. Roberts, A. G . Davies, and K. U. Ingold, J . Amer. Chem. SOC.,1974, 96, 554. l o R. Brandon, R. N. Haszeldine, and P. J. Robinson, J.C.S. Perkin 11, 1973, 1295. I7 R. Brandon, R. N. Haszeldine, and P. J. Robinson, J.C.S. Perkin 11, 1973, 1301. R. L. Kenney and G. S. Fisher, J. Org. Chem., 1974, 39, 682. l6

Photochemical, Radical, and Deoxygenation Reactions

(BUtO), Et,POH

209

Q,, +

(&(o'Et)z

P(OEt1,

P(OEt),

0

0

II

(28 1

(27)

y-Irradiation of diphenylphosphine sulphide gives the diphenylthiophosphinyl radical.l9 The e.s.r. spectrum of the radical was analysed. y-Irradiation of phenylphosphinic acid also produces radicals by P-H bond cleavage. Besides the expected radical (29), cyclohexadienyl radicals [having structure either (30a) or (30b)l and (31) were formed. From the *lPhyperfine coupling data for (31) it is evident that there is a strong hyperconjugative interaction between the C-P bond and the radical system. Despite this stabilizing factor,

radical (31) appears to be less stable than (30). y-Irradiation of glasses of phenylphosphonic acid does not produce radicals akin to (30) or (31) but radical (33).20This is presumably formed by deprotonation of the initially Phi(0)OH -+ (32)

Ph6O; (33)

formed radical (32). On annealing the glass, a process which allows radicalradical interactions to occur, cyclohexadienylradicals having a similar structure to (30) are formed. The energetics and reactions of phosphoranyl radicals still continue to attract attention. One of the rather surprising features of the energetics of phosphoranyl radicals is that the usual order of apicophilicity of substituent groups in phosphoranyl radicals is often very different to that observed for lo

M. Geoffroy, Helu. Chim. Acta, 1973,56, 1552. S . P. Mishra and M. C . R. Symons, Tetrahedron Letters, 1973, 4061.

Organophosphorus Chemistry

210

quinquecovalent-phosphorus compounds. For example, in radical (34),21the t-butoxy-group has been unequivocally shown to occupy the apical position. OBut

-P

I ,/dH

H ’I

H

For an analogous quinquecovalent compound a proton would have taken preference to the t-butoxy-group for occupation of the apical position. In other cases the substituent groups do not appear to have the same degree of apicophilicity in the radicals as they do in quinquecovalent compounds. Thus, as was reported last year,22the radicals (35a) and (35b) differ by only 2.9 kJ

(35a)

(35b)

mol-1 in energy. A value approaching 20 kJ mol-1 would be expected for an analogous quinquecovalent compound. These observations lead one to question the validity of trying to apply the rules which work for quinquecovalent compounds to phosphoranyl radicals. For quinquecovalentphosphorus compounds it has been pointed out that through-bond interactions which may involve lone-pair-lone-pair or lone-pair-c-bond interactions play a very important part in determining the energetics of a particular trigonal-bipyramidal structure. Now in the case of the phosphoranyl radicals we must consider lone-pair-half-filled-orbital interactions. Thus factors which are destabilizingfor the quinquecovalent compounds may in fact be stabilizing factors for phosphoranyl radicals. An analogous case taken from the chemistry of nitrogen compounds can be used to illustrate this point. Photoelectron spectroscopy23@ and n.m.r. methods 23b have demonstrated that in the lowenergy conformation of hydrazines, lone-pair-lone-pair interactions are avoided. On the other hand, in the radical cations of hydrazine, lone-pairhalf-filled-orbitalinteraction became of paramount importance as a stabilizing f a c t ~ r . ~Consideration ~c of the e.s.r. spectrum of (35a) shows that there is a very strong interaction between the lone-pair electrons of the nitrogen atom and the half-filled orbital of the phosphorus atom. For radical (35b) the *I

P. J. Krusic and P. Meakin, Chern. Phys. Letters, 1973, 18, 347.

** R. W. Dennis and B. P. Roberts, J. Organornetallic Chem., 1973, 47, C8. 9a

(a)S. F. Nelsen and J. M. Buschek, J. Arner. Chem. SOC.,1973, 95, 2011; (6) M. J. S. Dewar and W. €3. Jennings, ibid., p. 1562; (c) S. F. Nelsen and P. J. Hintz, ibid., 1972,94,

7108.

Photochemical, Radical, and Deoxygerzation Reactions

21 1

nitrogen hypedine coupling constant indicates that interaction is much weaker. The strong interaction in radical (35a) may either be a through-bond or through-space interaction. If it is in fact a through-space effect then one can understand why the nitrogen lone-pair in (35b) interacts with the half-filled orbital to a lesser extent than in (35a). Although in (35b) the lone-pair lies in the equatorial plane, it is not parallel to the half-filled orbital. From the e.s.r. spectra of (35a) and (35b) it is clear, as has already been discussed, that the amino-group in (35a) has a greater stabilizing effect upon the radical than in (35b). This effect will work in opposition to normal apicophilicityfactors. Thus in (35a) and (35b) these will favour the t-butoxy-group being apical, whilst the radical-stabilizingfactors will favour the amino-group being apical. These two effects, working in opposition, will tend to reduce the energy differencebetween the two species. With regard to the radical-stabilizingfactor, we predict from a knowledge of p-orbital sizes that amino-groups will stabilize phosphoranyl radicals more effectively than thio-groups, which in turn should be more effective than alkoxy-groups. Full details have now been published of the preparation and properties of the spirophosphoranyl radicals (36) and (37). 24 The structures were assigned

from a study of the e.s.r. spectra of the radicals. As was noted last year, radicals of the type (36) undergo pseudorotation only very slowly at temperatures as high as + 120 "C.As yet there is no explanation for this unprecedently high activation energy barrier to pseudorotation between trigonal pyramids of identical energies. It was also reported that phosphoranyl radicals can be trapped with the well-known spin trap 2-rnethyl-2-nitrosopropaney to give nitroxide radicals. Also, phosphoranyl radicals react with olefins, e.g. vinyl ethers, to give radicals that adopt the preferred conformation depicted by

D. Griller and B. P. Roberts, J.C.S. Perkin II, 1973, 1416. 8

212

Organophosphorus Chemistry

formula (38). This conformation is stabilized by a hyperconjugative interaction of the P-C bond with the half-filled orbital. Phosphoranyl radicals, e.g. (39), derived from ally1 phosphites undergo a cyclization reaction, e.g. to f

(39)

BU~OP(OCH,CH=CH~)~

J.

II

0

(40)

give (N),in addition to the more usual 8-scission reaction.26At temperatures around - 120 "C the phosphoranyl radicals are sufficiently stable for their e m . spectra to be recorded. By means of the reaction of t-butoxyl radicals with chlorophosphines, a wide variety of chlorophosphoranyl radicals have been prepared. 26 These radicals were characterized by their e.s.r. spectra, which showed slP and 3sCl and hyperfine splitting. For radicals such as (41) it could be shown that not only was the chlorine group in an apical position but

OBut (41)

also that, on the e.s.r. time-scale, the radical had a rigid structure. In all the other radicals studied, the chlorine atoms were found to occupy apical positions. Apparently chlorophosphoranyl radicals undergo the j3-scission reaction much less readily than non-halogenated phosphoranyl radicals. Thus (42) undergoes the reaction at low temperatures whereas (43)gives detectable amounts of butyl radicals only at temperatures as high as 25 "C.Even under these circumstances the butyl radicals may be generated via a sequence of

ButO$(OEt),CI -+ Bu'P(OEt), + C1' (43) Bu'OP(OEt), B''o'b (ButO),6(OEt), (44) w

B;'

+ (EtO),POBut

I1

0

A. G. Davies, M. J. Parrott, and B. P. Roberts, J.C.S. Chem. Comm., 1974, 27. D. Griller and B. P. Roberts, J.C.S. Perkin ZZ, 1973, 1339.

Photochemical, Radical, and Deoxygenation Reactions

21 3

reactions involving (44).The authors rationalized this reluctance of halogenophosphoranyl radicals to undergo /I-scission reactions as being due to the halogeno-group decreasing the electron density at the phosphorus atom. The e.s.r. spectra of phosphoranyl radicals bearing aryl substituents, e.g. (49, have been studied, and the conclusion has been reached 27 that, since most of the electron density is located in the aryl ring, such radicals have a structure more like (46) than (43, i.e. the radicals have a tetrahedral rather than a

OBu'

;/

.

,OMe

Ib

h

OMe (45)

(46)

trigonal-bipyramidal structure. A similar situation exists for the spirophosphoranyl radicals (47)28and ( 4 8 a - - ~ ) .In ~ ~the case of (49) the electron becomes localized on the n i t r o - g r o ~ p . ~ ~ A well-known reaction, which is often used for the preparation of phosphoranyl radicals, is of course the reaction of alkoxyl radicals with phosphites.

(47) R = OMe or NMe,

+q /f-+qi +qz P-.

P/kh (4W

P-.

Me

Me'Ae

Ph

(48b)

(48~) Ph

I

_3

$fi$\ *'

(49)

NO2

iFQ NO:

G. Boekestein, E. H. J. M. Jansen, and H. M. Buck, J.C.S. Chem. Comm., 1974, 118. R. Rothuis, J. J. H. M. Font Freide, and H. M. Buck, Rec. Trao. chim., 1973,92, 1308. R. Rothuis, J. J. H. M. Font Freide, J. M. F. van Dijk, and H. M. Buck, Rec. Trav. chim., 1974, 93, 128.

Organophosphorus Chemistry

214

It is therefore surprising to find that perfluoro-t-butoxyl radicals react with tridkyl phosphites to give radicals derived by hydrogen abstraction from a methylene group situated adjacent to an oxygen atom.**These products were characterized by e.s.r. spectroscopy. Hydrogen abstraction from the alkoxy-groups of alkyl phosphates by radicals is a well-documented reaction. Hydroxyl radicals have been shown, by means of e.s.r. spectroscopy, to react with glycerol-1-phosphate in this manner.31 However, the position at which radical attack occurs is pHdependent. Thus, at pH 5.4, (50) is formed, whereas at pH 8.5-11 (51) is

CH,OPO,H I

CH, OPO,H I I

pH5.4

CHOH

I CHOH 1

~

'OH

I

CH,OH

~HOH (50)

CH,OPO,'

CHOP0,'-

I CHOH I CH,OH

pH 8.5 - 11

'OH

+

CH,OP0,'-

I CHOH I CH,OH

-'CH

I I cHOP0,z? L CHOP0,2I I CH,OH CH,OH

I

CHO

~HOH

CH,OH

I

CHO

1

-+ 'CH

I CH,OH

+HPO,Z-

(553)

produced. This latter radical undergoes an elimination reaction to give (52). Radical (53), which is derived from glycerol-2-phosphate, undergoes elimination of the phosphate di-anion. Other alkyl radicals containing phosphorus substituents have been prepared by y-irradiation of silver diethylphosphate3z and magnesium diethylphosphate.33 y-Irradiation of (54) in either the powder form or as a single crystal at room

(H0)2PCH2CH2P(0H)2

I1

I1

0

0

yirradjation

'

OH ,--OH

I

2-p'

I

'CH,CH,P(OH), OH I1

0 (55 1 A. G . Davies, R. W. Dennis, B. P. Roberts, and R. C. Dobbie, J.C.S. Chem. Comm.,

(54)

1974,468.

A. Samuni and P. Neta, J. Phys. Chem., 1973, 77, 2425. a n W. A. Bernhard and F. S. Ezra, J. Phys. Chem., 1974, 78, 958. IaW. A. Bernhard and F. S. Ezra, J. Chem. Phys., 1974, 60, 1707; F. S. Ezra and W. A. Bernhard, ibid., p. 1711.

Photochemical, Radical, and Deoxygenation Reactions

21 5

temperature has been shown to give the phosphoranyl radical (55) in addition to two other radicals, which were not ~haracterized.~~ On the other hand, yirradiation of solutions of phosphoric acid in sulphuric acid gave the radical cation of phosphorous acid rather than the expected tetrahydroxyphosphoranyl radical.86 y-Irradiation of trimethyl phosphate gave the radical anion of the ester in addition to the (MeO)2P- 0radical. The previously reported formation of the tetrafluorophosphoranyl radical by y-irradiation of ammonium hexafluorophosphate has been shown to be in error; the radical formed was identified as the PF; radical.38The radical anions of phenylphosphonothionic dichloride and phenylphosphonic dichloride have been shown to lose chlorine atoms 3 7 to yield PhP(C1)S and PhP(C1)O radicals. Pulse radiolysis of HMPT in the presence of sodium bromide gives rise to a species having an absorption spectrum that is ascribed to a charge-transfer complex between the bromide anion and the HMPT radical cation.s8 As in past years, there have been reports of the reactions of quinones with ph~sphites.~@ It has been supposed that these reactions initially involve transfer of an electron from the phosphite to the quinone. Support for this postulate has come from the observation of the formation of paramagnetic species in the reactions by e.s.r. spectroscopy. A quantitative study has now shown that the rate of the electron process correlates with the reduction potential of the q~inone.~O The actual structures of the radicals produced in some of these reactions have also been e l ~ c i d a t e d .For ~ ~ example, triethyl phosphite reacts with 2,7-dinitrophenanthraquinone to give the quinone radical ion and ethyl radicals. Tris(dimethy1amino)phosphine reacts with phenanthraquinone to give the radical cation (56). This was identified by use of

the technique of spin trapping. Use of excess of the phosphine led to the formation of (57). Reaction of the phosphine with a@-unsaturatedketones gives the radical anions of the ketones, which can be trapped with 2-methyl-2nitrosopropane. Production of radical species in the reaction of trimethyl phosphite with acenaphthaquinone has been demonstrated by the fact that the quinone-phosphite mixture initiates the polymerization of styrene.4 2

as as ' 0

1 '

42

D. J. Whelan, Austral. J . Chem., 1973, 26, 1357. I. S. Ginns, S. P. Mishra, and M. C. R. Symons, J.C.S. Dalton, 1973, 2509. S . P. Mishra and M. C. R. Symons, J.C.S. Chem. Comm.,1974, 279. S . P. Mishra and M. C. R. Symons, J.C.S. Dalton, 1973, 1494. A. M. Koulkes-Pujo,L. Gilles, B. Lesigne, J. Sutton, and J. Y .Ga1,J.C.S. Chem. Comm., 1974, 71. M. M. Sidky, M. R. Mahran, and Y . 0. El-Khoshnieh, Tetrahedron, 1974, 30, 47. Y. Ogata and M. Yamashita, J . Org. Chem., 1973, 38, 3423. G. Boekestein, W. G. Voncken, E. H. J. M. Jansen, and H. M. Buck, Rec. Trau. chim., 1974, 93, 69. Y. Ogata and M. Yamashita, Bull. Chem. SOC.Japan, 1973, 46, 2208.

216

Organophosphorus Chemistry

Radical intermediates have also been detected in the reactions of tris(dimethy1amino)phosphine with ha loge no carbon^.^^ Thus the reaction of bis(p-nitrosopheny1)methyl bromide with the phosphine in solvents of relatively low polarity gave a benzylic radical, which was identified as (58) by Br

I

(Me,N),P-NBuf

I

0'

(59)

spin-trapping with 2-methyl-2-nitrosopropane. Radical (59) was also detected in these systems. When polar solvents were used for these reactions, radical intermediates could not be detected, and it was suggested that increasing the polarity of solvent leads to a greater preponderance of reaction via a heterocyclic process. The reactions of phosphites with peroxy radicals continue to attract attention because of the use of phosphites as anti-~xidants.~~ The autoxidation of a variety of hydrocarbons, e.g. tetralin, cumene, styrene, and cyclohexane, is inhibited by zinc dialkyldithiophosphates(60).4sIn order to assess the reactivity

of these compounds, rate constants for their reactions with t-butylperoxy radicals were determined. These quantitative data suggest that the mechanism of inhibition involves attack of the peroxy radical upon the zinc atom in a s H 2 process. The radical anion of 2-phosphanaphthalenehas been prepared by reduction of the parent heterocycle with potassium. Its e.s.r. spectrum was fully analysed.46 4 Deoxygenation Reactions Peroxides and Related Compounds.-Triphenylphosphine has been shown to react with the dioxetan (61) to give the quinquecovalent compound (62).*' This

decomposesto give an epoxide on heating. Several peroxides and polyperoxides react with alkyl- and aryl-phosphines in the presence of water.48Alcohols are

45

'7

G . Boekestein and H. M. Buck, Rec. Trav. chim., 1973, 92, 1095. K. J. Humphris and G . Scott, J.C.S. Perkin 11, 1974, 617; E. G . Chebotareva, G. D. Pobedimskii, D. G. Kolyubakina, N. A. Mukmeneva, P. A. Kirpichnikov, and A. G. Akhmadullina, Kinetics and Catalysis (U.S.S.R.), 1973, 14, 891 (Chem. Abs., 1974, 80, 2857). J. A. Howard, Y. Ohkatsu, J. H. B. Chenier, and K. U. Ingold, Canad. J. Chem., 1973, 51, 1543. C. Jongsma, H. G. de Graaf, and F. Bickelhaupt, Tetrahedron Letters, 1974, 1267. P. D. Bartlett, A. L. Baumstark, and M. E. Landis, J. Amer. Chem. SOC.,1973,95,6486. H. D. Holtz, P. W. Solomon, and J. E. Mahan, J. Org. Chem., 1973, 38, 3175.

Photochemical, Radical, and Deoxygenation Reactions Ph

Ph,P

f

M e G M e Me Me (6 1)

-

p t I ,Ph

P

0-0

I I )

217

MeXMe

Me 0 Me

+

Ph,PO

produced in these reactions. Ethyl benzenesulphenate reacts with tervalent phosphorus compounds, e.g. (63), to give diphenyl di~ulphide.~~

N-Oxides and Nitro-compounds.-Once again there have been reported several examples of the deoxygenation of N-oxides and nitro-compounds by tervalent phosphorus compounds. Compounds studied include (65),61(66),61and (67).62 0

phqv J* Ph&

II

\

(RO),P_

(RO),P:

+N-N+

* *

-4 \o(64)

(EtO),P+

c

N--N

nTH

NO2

0

(65 1

\

NO2 (661

‘ R

* R N\N Ar

oNo2 (67)

L. L. Chang and D. B. Denney, J.C.S. Chem. Comm., 1974, 84. B. A. Arbuzov, E. N. Dianova, and V. S. Vinogradova, Bull. Acad. Sci., U.S.S.R., 1973,

In

22, 1388. 61

**

T. Kametani, F. F. Ebetino, and K. Fukumoto, Tetrahedron Letters, 1973, 5229; J.C.S. Perkin I, 1974, 861. T. Nishiwaki, G. Fukuhara, and T. Takahashi, J.C.S. Perkin I, 1973, 1606.

Organophosphorus Chemistry

218

The substituted biphenyl (68) readily forms a carbazole (69), whereas (70) reacts to give a pho~phineimine.~~

Ph,P . Cumene

*

(-=j& H

'N=PPh,

5 DesulphurizationReactions The desulphurizationof benzylic sulphides by irradiating them in the presence of tervalent phosphorus compounds has again been used in the synthesis of paracy~lophanes.~~~ 65 A particularly elegant use of this reaction was made in the synthesis of (71), a compound which exhibits an intramolecular chargetransfer absorption band.5sThere have been several reports of the synthesis of

ha ti4

D. E. Ames, K. J. Hansen, and N. D. Griffiths, J.C.S. Perkin I, 1973, 2818. J. Bruhin and W. Jenny, Tetrahedron Letters, 1973, 1215. W. Rebafka and H. A. Staab, Angew. Chem. Internat. Edn., 1973, 12, 776.

Photochemical, Radical, and Deoxygenation Reactions

219

olefhs in which a crucial step was desulphurization of an intermediate, e.g. an episulphide,66or a thiadiazine.67, 6 8 Biquadricyclene (72) was synthesized by such a reaction.67

i, H,S-H,NNH, ii, Pb(OAc),

The reductive cleavage of several aryl disulphides to thiols by their reaction with triphenylphosphine in aqueous dioxan has been reported.6DSeveral examples have been reported of the cleavage by phosphines and phosphites of S -S and S-N bonds contained in heterocyclicring systems. Examples include (73) and (74).60

Other desulphurization reactions which probably involve ionic intermediates include those of (75)61and p-ketosulphides.6aThe reaction of the latter type of compounds is thought to involve enolate carbanions, and this (PhS),N

Ph,P

+

Ph,PN(SPh), --+

Ph,P=NSPh

SPh

68 69

6o

R. H. Mitchell, Tetrahedron Letters, 1973, 4395. H. Sauter, H.-G. Horster, and H. Prinzbach, Angew. Chem. Internat. Edn., 1973,12,991. A. P. Schaap and G. R. Faler, J. Org. Chem., 1973, 38, 3061. L. E. Overman, J. Smoot, and J. D. Overman, Synthesis, 1974, 59. 3. Goerdeler, J. Haag, C. Lindner, and R. Losch, Chem. Ber., 1974, 107, 502. J. Almog, D. H. R. Barton, P. D. Magnus, and R. K. Norris, J.C.S. Perkin I, 1974,853. D. N. Harpp and S. M. Vines. J. Org. Chem., 1974. 39. 647.

Organophosphorus Chemistry

220

idea appears to be substantiated by the isolation of 0-alkylationproduct (77) from the reaction of (76).

(76)

(77)

12 Physical Methods BY J. C.TEBBY

The abbreviations PIII, PIV, and P V refer to the co-ordination number of phosphorus, and the compounds in each subsection are 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 subst it uents, Ch represents chalcogenide 0 or S, and Y and 2 are used to indicate a wide variety of substituents. 1 Nuclear Magnetic Resonance Spectroscopy The difficult task of determining the preferred conformations of nucleotides and other complex naturally-occurring organophosphorus compounds has been studied by combined lH and 31P n.m.r. spectroscopy assisted by MO calc~lations.~ A review of 31Pn.m.r. spectroscopy has been p~blished.~ Chemical Shifts and Shielding Effects.-Phosphorus-3I. In this section, positive 31P chemical shifts (SP) are upfield from 85% phosphoric acid. A linear relationship between 8p and vapour pressure for elemental phosphorus in the gas phase has been r e p ~ r t e d Solvent .~ effects have also been 8p ofPIII compounds. The n.m.r. parameters of various protic and deuteriated phosphanes (1) at low temperatures have been reported.' The dn-pn contribution to SP of PIIr compounds has been estimated, and it decreases for the halogen derivatives with increase in atomic weight.8The relative importance of p - and d-orbitals in determining 8~ for several PIII, PIV, and P V compounds . ~ chemical shifts of comhas been calculated using the CNDO r n e t h ~ d The pounds of the type (2) are only slightly upfield of the corresponding methyl L. S. Kan, J. C. Barrett, P. S. Miller, and P. 0. P. Ts'O, Biopolymers, 1973, 12, 2225; R. H. Sarma, R. J. Mynott, F. E. Hruska, and D. J. Wood, Canad. J. Chem., 1973,51, 1843;R. H.Sarma and R. J. Mynott, J . Amer. Chem. Soc., 1973,95,7470. R. H.Sarma, C.-H. Lee, F. E. Hruska, and D. J. Wood, F.E.B.S. Letters, 1973, 36, 157;J. L. Alderf and S. L. Smith, J. Amer. Chem. Soc., 1971,93, 7305. F.Jordan, J. Theor. Biol., 1973,41,23;H. Cable, A. Rauch, and L. Pedersen, J. Pharm. Pharmacol, 1973,25,509. J. R. Van Wazer, Determination Org. Struct. Phys. Methods, 1971,4,323. G.Heckmann and E. Fluck, Mol. Phys., 1972, 23, 175. ' G . Krabbes and G . Grossmann, 2.Chem., 1971,11,470. ' P.Junkes, M. Baudler, J. Dobbers, and D. Rackwitz, 2. Naturforsch., 1972,27b, 1451. * A. S. Tarasevich and U. P. Egorov, Teor. i eksp. Khim., 1972,8, 235. M. A. Landau, A. S. Kabankin, and A. V. Fokin, Izvest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 10,2244.

221

222

Organophosphorus Chemistry

analogue Y2PMe or MePZ,,l0v l1 although it is claimed that the Ph2P group shields the phosphorus atom of the (R0)2Pgroup by 100 p.p.m.l0 The shielding effects on phosphorus of cyclic polyphosphines (3) were considerably less for the four-membered rings than the five-membered rings.12 Ring size had only a small effect on the amido- and thio-compounds (4; X = S or NMe), and BP remained in the range - 150 to - 163 p.p.m.13 8~ of PIV compounds. 31P n.m.r. evidence covering a wide range of salts has been presented to show that there is no delocalization through onium phosp h o r ~The ~ . series ~ ~ of ylides (5 ; n = 0-3) had dp values of - 70.8, - 62.5, - 35.6, and 2.1, re~pective1y.l~ The contribution of d,,-p,, conjugation in

+

iminophosphoranes (6), as estimated by the application of the Letcher-Van Wazer theory, increased with (a) increasing electronegativity of the Psubstituents and (b) decreasing electronegativity of N-substituents.l 6 These conclusions were challenged when experimental data showed an upfield shift of BP with increasing n-bond-order of the PN b0nd.l‘ See also p. 251 of ref. 18d. Refinements were introduced into the calculations which eliminated some of the problems without altering the basic concepts of the theory.19 The modifications have been extended to symmetrical phosphorus compounds and cyclic chlorophosphazenes.20The similarities of 6p (- 25.8 and - 26.1 p.p.m.) for the cyano-stabilized imino- and methylene-phosphoranes (7) and (8) have U. L. FOSS, Yu. A. Veits, V. V. Kudinova, A. A. Borisenko, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.),1973, 43, 9984. l1 Yu. A. Veits, A. A. Borisenko, V. L. Foss, and I. F. Lutsenko, J. Gen. Chem. (U.S.S.R.), 1973, 43, 439; E. E. Nifant’ev, A. I. Zavalishina, and I. V. Komlev, J. Gen. Chem. (U.S.S.R.),1971, 41, 1457. l a H. G . Ang, M. E. Redwood, and B. 0. West, Austral. J. Chem., 1972,25, 493. l 8 E. E. Nifant’ev, A. A. Borisenko, A. I. Zavalishina, D. A. Predvoditelev, I. V. Komlev, and S. F. Sorokina, Zhur. obshchei Khim., 1971, 41, 2841. l4 G. P. Schiemenz, Phosphorus, 1973, 3, 125. l 6 H. Schmidbaur, W. Buchner, and D. Scheutzow, Chem. Ber., 1973, 106, 1251; K. Issleib, M. Lischewski, and A. Zschunke, Org. Magn. Resonance, 1973, 5, 401. l o A. S. Tarasevich and Yu. P. Egorov, Teor. i eksp. Khim., 1971, 7 , 828. lT E. S. Kozlov and S. N. Gaidamaka, Teor. i eksp. Khim., 1972, 8, 420. ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, (a) 1970, Vol. 1, Ch. 11; (6) 1971, Vol. 2, Ch. 11; (c) 1972, Vol. 3, Ch. 11; ( d ) 1973, Vol. 4, Ch. 11; (e) 1974, Vol. 5, Ch. 11. Yu. P. Egorov and A. S. Tarasevich, Teor. i eksp. Khim., 1972, 8, 422. A. S. Tarasevich and Yu. P. Egorov, Teor. i eksp. Khim., 1973, 9, 73. lo

Physical Methods

223

(7 1

(8)

(9 1

(10)

been discussed.21 As expected, the phenylethynylgroup shields the phosphorus atom in Prv compounds, e.g. (9) and (10),22as already noted for PII1 compounds.lse The different chemical shifts of thiolo- and thiono-isomers were amply demonstrated by (11) and (12), which had 6p of -74.6 and - 120.6

zrSEt

Z = S

I OEt

0

(11)

(12)

Ch

I l p

Ch

II

MeP ‘OR

RP(SEt),

(13)

(14)

p.p.m., re~pectively.~~ In a series of methylphosphonyl chlorides (13) the number of B-carbon atoms in the alkoxy-group exerted a major effect on the chemical shifts.24The replacement of phenyl by cyclohexyl in the compounds (14; Ch = 0) caused 8p to shift 47.5 p.p.m. downfield to appear at -100 p.p.m., but in the corresponding sulphides (14; Ch = S) the downfield shift ~ ~ parameters are was only 21.5 p.p.m. (from - 80.5 to - 102 p . ~ . m . ) .N.m.r. also reported for a series of PIV compounds (15 ) , 26 cyclic phosphonates (16), 27

(15)

(16)

and a-hydroxymethyl- and a-hydroxybenzyl-phosphonyl compounds.28 The n.m.r. data on monoalkyl and alkylenediphosphoryl compounds and their complexes have been reviewed.29The phosphorus atom in phospholipids is deshielded compared to that in phosphatidylcholine, an effect attributed to hydrogen-bonding to the phosphoryl group in the former.3o H. Koehler and B. Kotte, 2. Chem., 1973, 13, 350. E. Fluck and N. Seng, 2. anorg. Chem., 1972, 393, 126. J. R. Corfield, R. K. Oram, D. J. H. Smith, and S. Trippett, J.C.S. Perkin I, 1972, 713. A. A. Abduvakhabov, A. A. Sadykov, and K. M. Zuparova, Doklady Akad. Nauk Uzbek. S.S.R., 1973,30,41; A. A. Abduvakhabov, K. Inoyatova, A. A. Sadykov, and A. S. Sadykov, Doklady Akad. Nauk Uzbek. S.S.R., 1973,30,48. M. Yoshifuji, S. Nakayama, R. Okazaki, and N. Inamoto, J.C.S. Perkin Z, 1973, 19, 2065. S. P. Khranenko, L. K. Chuchalin, A. I. Rezvukhin, Z . N. Mironova, B. I. Peshchevitskii, and E. A. Gal’tsova, Zzuest. sibirsk. Otdel. Akad. Nauk, Ser. khim. Nauk, 1972, 72, 3. B. A. Arbuzov, A. 0. Vizel, K. M. Ivanovskaya, and E. I. Gol’dfarb, J. Gen. Chem. (U.S.S.R.), 1973, 43, 2125. L. Maier, Z . anorg. Chem., 1972, 394, 117; H. Timmler and J. Kurz, Chem. Ber., 1971, 104, 3740. W. E. Stewart and J. H. Siddall, Ion Exchange, Solvent Extr., 1973, 3, 83. T. 0. Henderson, and T. Glonek, Biochemistry, 1974, 13, 623.

I1

=4

z5

pe

‘7

*a

224

Organophosphorus Chemistry

6~ of P V compounds. The oxaphosphetan intermediates of the Wittig reaction, such as (19,have 6~ in the region 63-74 p.p.m., which is upfield of themual range of acyclic alkyltriphenyloxypho~phoranes.~~ This contrasts with the 18d Chemical shifts of downfield shift produced by five-membered

(1 7)

(19)

(18)

fluorophosphoranes (18) agreed with those calculated from the relationship dp = 1430.8-(734Pp)-(132.2Pd), where P p and Pa are the paramagnetic components of the magnetic shielding constant due to p- and d-electron~.~~ The chemical shifts of some mixed chlorofluorophosphoranes (1 9) have been reported.34 Carbon-I3. Aromatic methyl resonances have been assigned by singlefrequency decoupling of the adjacent aromatic protons.35The phosphorinanol (20) was identified by the steric compression between the axial P-methyl group and the axial &protons, which shield the methyl, C-3, and C-5 carbon atoms.S6 The tautomers (21) and (22; 2 = 0 or lone-pair electrons) were readily

(20)

(21)

(22)

(23)

distinguished by the chemical shifts of the enolic carbon The acarbons of the ylides (23) have 6 g M S values in the range 29-33 p.p.m., which are comparable with those of the corresponding salts but well upfield of those of a vinyl model compound. The triphenylphosphonium group has its own characteristic shielding effect on 6~ but it does not interact with other substituents to produce non-linear effects.3813Cn.m.r. spectroscopy has also been used to determine the position of phosphate groups in natural a1 8'

aa a6

*'

E. Vedejs, K. A. J. Snoble, and P. L. Fuchs, J . Org. Chem., 1973,38,1178; E. Vedejs and K. A. J. Snoble, J. Amer. Chem. SOC.,1973, 95, 5778. G. Buono and G. Peiffer, Tetrahedron Letters, 1972, 149. M. A. Landau, A. S. Kabankin, and A. V. Fokin, Zhur.$z. Khim., 1973, 47, 2916. H. Binder, 2.anorg. Chem., 1971, 384, 193. S. Sorenson, M. Hanson, and H. J. Jakobsen, J. Magn. Resonance, 1973, 12, 340. S. I. Featherman and L. D. Quin, Tetrahedron Letters, 1973, 1955. L. D. Quin and R. C. Stocks, J. Org. Chem., 1974, 39, 686. G. A. Gray, J. Amer. Chem. SOC.,1973, 95, 5092, 7736. P. A. J. Gorin, Canad. J . Chem., 1973, 51, 2105; J. R. Que, M. Cashel, G . R. Willie, J. W. Bodley, and G. R. Gray, Proc. Nut. Acad. Sci. U.S.A., 1973, 70, 2563.

Physical Methods

225

Fluorine-19. Fluorine chemical shifts have been used with some effect to study bonding in organophosphorus compounds.lsa*1 s A ~ comparison of the shifts + + for the compounds (24; Y = Me3P, Me3N, or Br) showed least electron

(24 1

(25 1

withdrawal by the phosphonium group, which was accounted for by its possessing the smallest negative hyperconjugation of the three groups, i.e. smallest contribution of (25) to its resonance hybrid.40 Hydrogen-1. Bases such as phosphites deshield the acidic proton of phenols, alcohols, and chloroform. Exceptions are bases like pyridine, which have a large magnetic anisotropy. One possible explanation is that the shift is due primarily to the distortion of charge around the proton produced by the donor’s lone pair of electron^.^^ The reactivity of orthophosphate monoesters Further to hydrolysis was related to 6011 of the protonated leaving work has been completed on the stereochemical assignments of substituted 0 0

\

H

/c=c\,

/H

vinyl phosphates, i.e. derivatives of 44a In any pair of isomers the proton cis to the phosphoryl group resonates to lower field than the corresponding trans-proton. The additive substituent chemical shift (S.C.S.) for a group on the carbon-carbon double bond is -0.7 p.p.m. for a h C t 8 and -0.41 p.p.m. for a h trans.43 Studies of trinucleoside diphosphates have shown that the methyl protons on the terminal residues are shielded relative to those of dimers 4b Studies of Equilibria, Shift Reagents, and Solvent Effects.-Several studies of halogen-exchange equilibria have been reported, e.g. the exchange between phosphoryl, phosphonyl, and phosphinyl halides,4 s PI11 and PIV halides (27)

.

W. Adcock, M. J. S. Dewar, and B. D. Gupta, J. Amer. Chem. SOC.,1973,95, 7353. F. L. Slijko and R. S. Drago, J. Amer. Chem. SOC.,1973, 95, 6935. 4 a Y.Murakami and J. Sunamoto, J.C.S. Perkin ZI, 1973, 1235. C. B. C. Boyce, S. B. Webb, L. Phillips, and P. A. Worthington, J.C.S. Perkin I, 1973, 288 1. ’* (a) E. M. Gaydou, Canud. J. Chem., 1973, 51, 3412; (b) L. S. Kan, J. C. Barrett, and P. 0. P . Ts’O, Biopolymers, 1973, 12, 2409. 46 J. G. Riess, J. C. Elkaim, and S. C. Pace, Inorg. Chem., 1973, 12, 2874. 40

41

226

Organophosphorirs Chemistry

and (28),4sand PI11 or PIV halides with dihalogeno~ilanes.~~ Reports on the self association of various monothio-acids (29) p8 and the proton-exchange rates of Y

0

0

0

II

II

ll

CH,PF, + CH,PCL, @ CH,PF, + CH,PFCl (27)

+ CH,PCI,

' 2

(28) PTvCHY-COZ

S

\p/

H O ' (29)

=F+

P"CY=CZOH

Y,PHO

(32)

(30)

(31)

(30) with deuterium oxidePehave also appeared. Several studies of keto-enol systems (3 1)~ ( 3 2 )have been described for phosphonates,60 phosphine oxides,61and phosphonium salts.62The large upfield shift of the OH resonance upon dilution, which indicates reduced intermolecular hydrogen bonding, was used as evidence for a trans geometry for the enol of the phosphonium salts.62 An equilibrium involving the spirophosphoranes (33; Y = NMe,) and (33;

(3 3)

(34)

(35)

Y

= PhCO,) has been reported.53The changes of 8~ of phosphine oxides (34) in aqueous sulphuric acid were described by the amide acidity function HA, but the changes of 8~ required a new function, which increased more slowly than HAor H o . Dimethyl ~ ~ sulphoxide strongly hydrogen-bonds to alcoholic protons and inhibits proton exchange. Coupling often appears, and SOH can be used as a structural parameter in linear free-energy relationships, e.g. in the hydrolysis of the phosphate (35).65Separate signals for the amino-protons of aqueous 2',3'-cyclic cytidine monophosphate were observed below 0 "C.One is attributed to a proton which is hydrogen-bonded to free solvent; the other is

J. G. Riess, J. C. Elkaim, and A. Thoumas, Phosphorus, 1973, 3, 103. K. Moedritzer and J. R. Van Wazer, Inorg. Chem., 1973, 12, 2856. 4 8 V. K. Pogorelyi, I. I. Kukhtenko, L. S. Butorina, and T. A. Mastryukova, Doklady. Akad. Nauk S.S.S.R.,1974, 214, 385. I. V. Shilov and E. E. Nifant'ev, J. Gen. Chem. (U.S.S.R.),1973, 43, 583. r 0 A. N . Pudovik, R. D. Gareev, and S. E. Shtil'man, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1628. lil A. I. Razumov, B. G. Liorber, M. P. Sokolov, V. V. Moskva, G. F. Hazvanova, T. V. Zykova, L. A. Chemodanova, and R. A. Salakhutdinov,J. Gen. Chem. (U.S.S.R.), 1973, 43, 570. I * T. A. Mastryukova, I. M. Aladzheva, P. V. Petrovskii, E. I. Matrosov, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.),1973,43, 985. D. Bernard and R. Burgada, Tetrahedron Letters, 1973, 3455. N . K. Skvortsov, G. F. Tereshchenko, B. I. Ionin, and A. A. Petrov, J. Gen. Chem. (U.S.S.R.), 1973, 43, 976. Y.Murakami and J. Sunamoto, J.C.S. Perkin II, 1973, 1231. w

227

Physical Methods

attributed to a proton involved in an intermolecular complex.66Resonances corresponding to protons adjacent to nitrogen and protons adjacent to the phosphate group appeared in the spectrum of lecithin after water had been added.67Solute-solvent interactions involving tetraphenylphosphonium ions are also reported.68 Shift reagents have been used to study the stereochemistry of the cyclic phosphites (36)69 and (37).60 In the latter case it was concluded that the

0 "

'OMe (36)

(38 1

(3 7)

reagent induced a shift of the equilibrium towards the conformation with a pseudo-axial phosphoryl group. A study of ketonic phosphine oxides indicated that Eu(dpm), forms complexes preferentially with the PO group, producing larger shifts for the protons a to the PO group.61 The splitting produced by tris-[3-trifluoromethylhydroxymethylene]-d-camph estabished the chirality of the spirophosphorane (38),62 Pseudorotation.-The methoxyphosphorane (39; X = OMe) is sufficiently stable at - 80 "Cto exhibit non-equivalent methyl groups and PH coupling to the methoxy protons. However, upon raising the temperature, dissociation occurs before any pseudorotation effects can be The corresponding fluorophosphorane (39; X = F) is dissociated at -85 oC.04Studies of a

Me

(39)

(40)

number of trifluoromethylphosphoranes(40) had established that fluorine and chlorine atoms are more apicophilic than the trifluoromethyl group, which in turn is more apicophilic than hydrogen or alkoxy- or amino-groups.6s It has B. McConnell and P. C. Seawell, Biochemistry, 1973, 12, 4426. Y . H. Shaw, L. S. Kan, and N. C. Li, J. Magn. Resonance, 1973,12,209. J. F. Coetzee and W. R. Sharpe, J. Phys. Chem., 1971,75, 3141. 6 0 J. A. Mosbo and J. G . Verkade, J. Amer. Chem. SOC.,1973,95,4659. g o T . Sat0 and K. Goto, J.C.S. Chem. Comm., 1973, 494. Y . Kashman and 0. Awerbouch, Tetrahedron, 1971, 27, 5593. I* D. Houalla, M. Sanchez, and R. Wolf, Org. Magn. Resonance, 1973, 5, 451. ga H. Schmidbaur, H. Stuehler, and W. Buchner, Chem. Ber., 1973, 106, 1238. H. Schmidbaur, K. H. Mitschke, W. Buchner, H. Stuehler, and J. Weidlein, Chem. Ber., .SO

67

1973, 106, 1226. g6

J. W. Gilje, R. W. Braun, and A. H. Cowley, J.C.S. Chem. Comm., 1973, 813; R. G. Cavell, D. D. Poulin, K. I. The, and A. J. Tomlinson, J.C.S. Chem. Comm., 1974, 19.

228

Organophosphorus Chemistry

been pointed outss that the variable-temperature spectra of (41; R = Me, Y = H) and (41; R = H, Y = OEt) indicate that hydrogen is more apicophilic than oxygen, and that this evidence has been supported by

calculations on H2PF3.The barriers to pseudorotation in the aminotetraoxyphosphoranes (42; Y = CF3) have been found to be remarkably insensitive to the nature of the R groups compared to the changes of the basicity of the secondary amines R2NH.67MO calculations are reported to favour a Berry mechanism for the pseudorotation of pentafluorophosphorane.68 Restricted Rotation.-A series of PI11 and PIV mono-, di-, and tri-t-butyl compounds have been Evaluated AG* values for restricted rotation of the tertiary butyl group were in the range 6-10.5 kcal mol-l; the sulphide (43) had the highest barrier. The restricted rotation reported earlier 18c for triso-tolylphosphine selenide has been retracted.70 Non-equivalent N-methyl groups were observed for (44)71 and (45),72 indicating restricted rotation 0

.c(

,MeA

Me "$$jut S (43)

Me

N

I

MeB (441

I

Me (45 1

about the P-N bond. MO calculations suggest that rotations about the P-N bond of PHINHBand PF,NH2 are coupled to inversion at the nitrogen atom.s8 It is also interesting to note that it was found unnecessary to invoke PN d,-p, bonding for compounds such as (46) and similar PI11 compounds in order to explain changes in the 16NHcoupling constants of these compounds and the corresponding silylamines.73This does not rule out the presence of n-bonding, and indeed theoretical and n.m.r. studies of pseudorotation indicate significant

7a

R. K. Oram and S. Trippett, J.C.S. Perkin I, 1973, 1300. S . Trippett and P. J. Whittle, J.C.S. Perkin I, 1973, 2302. A. Strich and A. Veillard, J. Amer. Chem, SOC.,1973, 95, 5574. C. H. Bushweller and J. A. Brunelle, J. Amer. Chem. SOC.,1973,95, 5949. R. A. Shaw, M. Woods, W. Egan, and J. Jacobus, Chem. and Znd., 1973, 532. J. Ernsley and J. I<. Williams, J.C.S. Dalton, 1973, 1576. R. G.Cavell, R. D. Leary, A. R. Sanger, and A. J. Tomlinson, Inorg. Chem., 1973,12,

7a

1374. A. H. Cowley and J. R. Schweiger, J. Amer. Chem. SOC.,1973, 95, 4179.

OD 70 T1

229

Physical Methods

(4 7)

(46)

(48)

dn-pn bonding to radial groups of Pv compounds. However, the failure to detect restricted rotation about the P-aryl bonds of (47) and (48) 66 may be due to insufficient difference between back-bonding by the aryl groups in the apical and radial planes. Inversion, Non-equivalence, and Configuration.-Lowering of the inversion barrier of the acylphosphine (49)by conjugation of the phosphorus lone pair of electrons with the carbonyl group was confirmed by the sensitivity of inversion to the nature of R.74Non-equivalence of the apical fluorine atoms in F

RCOPPr',

a series of fluorophosphoranes (50) at - 30 to - 100 "C was attributed to the asymmetry of the CHMeY group when Y is an alkyl group other than methyl.7s Spin-Spin Coupling.-Subtraction of the 31P-decoupled spectrum from the single-resonance spectrum using a digital accumulator was used to reveal the hidden vinylic protons of ~is-(51).?~ The Overhauser effect has been used to 0

II

(MeO),FCH=CHPh (51)

study the conformations of adenosine monophosphates.7 7 Examples of 'through-space' coupling are more common for fluorine78 than phosphorus,18b and a previously quoted example of 'through-space' PH coupling in a tungsten complex was ruled out when the signs of the coupling constants of model compounds were taken into R. G. Kostyanovskii, A. A. Fomichev, L. M. Zagurskaya, and K. S . Zakhorov, Bull. Acad. Sci. U.S.S.R.,1973, 1870. 7 6 D. U. Robert, D. J. Costa, and J. G. Riess, J.C.S. Chem. Comm., 1973, 745. U. D. Nechaev, Yu. V. Belov, Yu. L. Belov, Yu. L. Kleiman, N. V. Morkovin, and B. I. Ionin, Teor. i eksp. Khim., 1971, 7 , 424. '' D. Z. Tran and C. Chachaty, Biochim. Biophys. A m , 1974, 335, 1. F. B. Mallory, J. Amer. Chem. SOC.,1973, 95, 7747. 7 9 J. D. Kennedy, W. McFarlane, and D. S . Rycroft, Inorg. Chem., 1973, 12, 2742. ?4

230

Organophosphorus Chemistry

JPPand JPM.The differences of IJpp from -236 to - 310 Hz in the cyclic phosphine (52) were attributed to stereochemical effects.80The a-alkoxy 13C

Me

I

fir

P/Me M>p

/q-p\ Me Me

(RcH20), PCH, P(OCH2R),

(52)

(53)

signal of neat (53) corresponded to an AA’X system (quintets), and upon dilution with benzene or cyclohexane it changed to a clear doublet. Spectral simulations indicated that JPCPdecreased from 5 to 0.5 Hz upon dilution.81 The proton signals of MezN or RCHzO groups of cyclophosphazenessuch as (54) 83 and (55) 8 3 exhibit virtual coupling (i.e. they appear as a mound flanked

c1

“,y

/p=N\ N

/ c1

\

N=P\

/

c1

/

Ap\

NMe,

/

NMe,

(54)

(55)

(56)

by two peaks) when the adjacent phosphorus atom($ have identical environments to the phosphorus atom bearing the Me,N or RCHzOgroups. The effect has been used to assist structural assignments. Derivatives such as (56)84 do not possess suitable lH resonances. Phosphorus substituent parameters ;E have ~ triphosphazenes. been defined and evaluated for estimating 2 J of~ cyclic Values of R are approximately proportional to the electronegativity of the substituent.8 5 Although JPSPdid not vary from 71 k 1 Hz when the spectrum of (57) was determined in different solvents, BP varied by 34.5 p.p.m.86The P-Se and P-Te coupling constants are governed mainly by the inductive

a1 8s

84

P A

Me,PSe

F,HPSe

F,PNH,

(5 7)

(58)

(59)

(60)

J. P. Albrand, D. Gagnaire and J. B. Robert, J. Amer. Chem. SOC.,1973, 95, 6498. M. Fild and W. Althoff, J.C.S. Chem. Comm., 1973, 933. G. J. Bullen, P. E. Dann, V. B. Desai, R. A. Shaw, B. C . Smith, and M. Woods, Phosphorus, 1973, 3, 67. T. P. Zeleneva, I. V. Antonov, and B. I. Stepanov, J. Cen. Chem. (U.S.S.R.), 1973, 43, 1000. 1. B. Telkova, V. V. Kireev, and V. V. Korshak, J. Gen. Chem. (U.S.S.R.),1973, 43, 1247; A. A. Volodin, V. V. Kireev, V. V. Korshak, and A. A. Fomin, J. Gen. Chem. (U.S.S.R.),1973, 43, 2198. K. Schumann and A. Schmidpeter, Phosphorus, 1973, 3, 51. G. Heckmann and E. Fluck, 2. Naturforsch., 1971, 26b, 982.

Physical Methods

231

effects of the P-substituent~.~~* 8s The coupling constants of the selenides varied from - 684 for (58) to - 1046 Hz for (59).87The P-16N coupling constant of (60) was +73 Hz, which corresponds to a reduced value for KPNof - 148 Hz." JPC.One-, two-, and three-bond P-C coupling constants have been reviewed ~ for a wide range of organophosphorus In general, 2 J is~lowest (2-11 Hz) and ~ J Phighest C (35-150 Hz)for P I V compounds and halogenophosphines. However, all three coupling constants fall in the range 9-28 Hz for acyclic aliphatic phosphines. The value of 2 J for ~ (61) ~ was +32.9 Hz, which is larger than the usual range (18-28 Hz) for aromatic phosphines.@l

(61)

(62)

A study of the cyclic phosphine (62) showed that the one-bond P-C coupling constants were all larger for the configuration shown but that couplings through two bonds were observed only for the isomers with an equatorial ~ ~ methyl The enolic P I V compound (22; Z = 0)possessed a 2 J value of 45 Hz, which is more than double that (21 Hz) of the keto-form (21; Z = 0),which is itself above the usual range for acyclic P I V The P-C couplings to the phenyl carbon atoms of the ylides (63) and their salts are similar, indicating that the electronic differences lie mainly in the ylidic +

+

Ph,&-kRCO,Et

(63)

Ph,P-CH,CO (64)

ZEt

Ph, PCH=CHOH

(65 1

(66)

carbon.38This is supported by the much larger values of ~ J P(120-130 C Hz) of the ylides compared to the salts, e.g. ~ J PisC55.5 Hz for (64).sp Hybridization C 99.2 Hz for (65), must be largely responsible of the a-ylidic carbon, if ~ J P is for the magnitude of the coupling constant. HMO calculations on the ylide (66) agreed with a predominantly ylidic structure, as shown, rather than an ylene structure.9a W. McFarlane and D. S. Rycroft, J.C.S. Dalton, 1973, 2162. I. A. Nuretdinov and E. I. Loginova, Izuest. Akad. Nauk S.S.S.R., Ser. khim., 1973, 2827. D. W. W. Anderson, J. E. Bentham, and D. W. H. Rankin, J.C.S. Dalton, 1973, 1215. B o J. R. Llinas, E. J. Vincent, and G. Peiffer, Bull. SOC.chim. France, 1973, 3209. O 1 S. Sorensen, R. S. Hansen, and H. J. Jakobsen, J. Amer. Chem. SOC.,1973, 95, 5080. B9 Z . Yashida, S. Yoneda, and Y. Marata, J. Org. Chem., 1973, 38, 3537.

87

232

Organophosphorus Chemistry

Stereochemical effects have been observed for JPOCand used to estimate the conformations of derivatives of (67).93s9 4 The coupling constant for the

P-methoxy-4,5-dimethyl derivativewas large and positive when the phosphorus lone pair of electrons and the C - 0 bond were cis orientated and small for the trans orientation. J P C ~The H . dependence of PCH coupling constant on dihedral angle was used to assign diastereomers of heterocyclic phosphines such as (68; Y = CH, or

(68)

CO, X = 0 or NR).96A very low value of 2 J (+0.1 ~ Hz) ~ for ~ the vinyl compound (69) was attributed to the trans orientation of the lone pair of electrons to the E-CHbond. The vinylphosphine(70), which is not restricted to the above conformation, shows a geminal coupling constant of 15.7 Hz.gs Calculations indicate that this coupling constant can be negative for antiparallel orientation^.^' Also, methylation of (69) and (70) gave salts possessing

+

H

\/’” =P?=“\ H

H Me&. Me,N-P:

\/c-c/ \”

BLlt

(69)

Me,”

“Me, (70)

Ph

Ph

I I+ PhMeNP=N-PNMePh

I

I

Ph

Ph

(71)

+

JPCH values of 15.7 and +20.6 Hz, respectively. The geminal coupling constant to the proton on the ylidic carbon of ( 5 ; n = 0 ) is + 6.5 Hz and steadily increases in magnitude as P-methyl groups are replaced by dimethylamino-groups, which suggests that JPCHis also positive for the ylides ( 5 ;

O6

9g OT

E. E. Nifant’ev, A. A. Borisenko, and N. M. Sergeev, Doklady Akad. Nauk S.S.S.R., 1973,208,651. M. Haemers, R. Ottinger, D. Zimmermann, and J. Reisse, Tetrahedron Letters, 1973, 2241. A. Zschunke, A. Hauser, and H. Oehme, 2.Chem., 1973,13, 310. R. M.Lequan and M. P. Simonnin, Bull. SOC.chim. France, 1973,2365. R. M.Lequan and M. P. Simonnin, Tetrahedron, 1973,29,3363.

Physical Methods

233

1-3).16 The PCH coupling constant was 9 H z for the related ylide (71).9sIt has been reported that JPCH is only positive for fluoro- and chloroderivatives of (72).lScIn contrast, JPCH of the vinyl analogue (73) is negative if It =

0

II EtPY, (72)

0 &C=CHPF,

Me,PFi (74 1

(73 1

(75 1

~JPF is Geminal PCH coupling constants in PVI compounds (74)loo and (75)lo1were 10.7 and 20.5 Hz, respectively. The large PCCH coupling constants that have been observed for phosphines when the lone pairs of electrons are close to the @-hydrogens16Cwere also demonstrated by the spectra of t-butyl phosphines (76) at low temperature. At

(76 1 - 125 "Cthe coupling was 13.4 Hz to the MeBprotons and 2.4 Hz to the trans MeAprotons in tri-t-butylpho~phine.~~ Other t-butyl phosphines gave similar spectra. The assignment of stereochemistry of the silyl compound (77) was made on the basis of 3JPH = 8.5 Hz, which was compared with the cis- and trans-couplings of 7.5 Hz (JPHA) and 0.5 Hz (JPHB)for the phosphonate (78).lo2Neither the effect of the lone pair of electrons nor any changes in the conformation of the ring of the alternative isomer of (77) were considered. Further work on the dependence of the PCCH coupling constants of phos-

k (77 1

H (78)

phonates on the dihedral angle has been based on norbornyl derivatives.lo3 The coupling constant is 18 Hz when the dihedral angle is 0", zero at go", V. Yu. Kovtun, V. A. Gilyarov, and M. I. Kabachnik, Bull. Acad. Sci. U.S.S.R.,Chem. Sci., 1971, 2095. V. I. Zakharov, Yu. V. Belov, B. I. Ionin, and A. A. Petrov, Doklady Akad. Nauk S.S.S.R., 1973, 209, 1343. l o o M. Wieber and K. Foroughi, Angew Chem. Internat. Edn., 1973, 12, 419. l o l W. Stadelmann, 0. Stelzer, and R. Schmutzler, J.C.S. Chem. Comm., 1971, 1456. l o * C. Couret, J. Satge, J. Escudie, and F. Couret, J. Organometallic Chem., 1973, 57, 287. l o a C. Benezra, J. Arner. Chem. SOC.,1973, 95, 6890. pa

234

Organophosphorus Chemktry

and rises to a maximum of 41 Hz at 180". For vinylphosphonates (79) the considerably larger trans-PCCH coupling across the double bond compared to the cis-coupling can be complicated by the coupling constant's additional dependence on the position and electronegativityof substituentson the double lsb. l a c Another fairly high value for the trans-PCCH coupling constant l 8 c has been observed, i.e. 56.5 Hz for the bromophosphonate

The coupling constants to aromatic protons have been recorded for (81)lo6 and (82),lo7and four-bond PHA coupling constants of 13 Hz for (83) lotiand 1.5 Hz for (84) have been noted.los JPCXH. The n.m.r. spectra of phosphonyl-containing carbohydrates in dimethyl sulphoxide exhibit splittings, due to JPCOH, which are dependent on the PCOH dihedral angles. The coupling constant is 14 Hz at 0",falling to zero at 90" and rising to a maximum of 31 Hi at 180°.109In other solvents the coupling is dependent upon dilution, which alters intermolecular hydrogen bonding, as has been observed for (85).110 L. Maier, 2. anorg. Chem., 1972, 394, 111; D. Danion and R. Carrie, Bull. SOC.chim. France, 1972, 1130; C . E. Griffin and W. M. Daniewski, J . Org. Chem., 1970, 35, 1691. l o 6 R. C. Elder, L. R. Florian, E. R. Kennedy, and R. S. Macomber, J. Org. Chem., 1973,

lo4

38, 4177.

P. Dembech, G. Seconi, P. Vivarelli, L. Schenetti, and F. Taddei, Org. Magn. Resonance,

log

1972, 4, 185. l08 10s

l1O

G. Haegele, K. Diemert, and W. Kuchen, 2. Naturforsch., 1973, 28b, 185. Z. Yoshida, S. Yoneda, and T. Yato, Tetrahedron Letters, 1971, 2973. H. Paulsen, and W. Greve, Chem. Ber., 1973, 106, 2124. A. N. Pudovik, R. D. Gareev, A. B. Remizov, A. V. Aganov, G. I. Evstaf'ev, and S. E. Shtil'man, J. Gen. Chem. (U.S.S.R.), 1973, 43, 562.

235

Physical Methods 0

It

(RO),PCMeC(N, )CO,R

I

OH (85 1

JPXCH. The POCH coupling constant of (86) is 19.6 Hz, which is nearly double that of its isomer with an axial amino-group. Thus, like JPCCH, the coupling is dependent on the orientation of the lone pair of electrons on phosphorus as well as the dihedral angle of the POCH group.lll This complication is absent

from the PIv compounds (87). In this series of compoundsJ ~ Hand A JPHB were usually ca. l O H z , but extreme values of 8 and 14Hz, respectively, were observed for (87; X = S, Y = Me,") and 22 and 5 Hz, respectively, for (87; X = S, Y = C1 or PhO).ll2 Conformational analysis of (88)ll5 and

(89) 114 has utilized JPXCH. It has been reported that the methyl resonance of (90) is a simple triplet, whereas for (91) it appears as a p s e ~ d o - t r i p l e tThe .~~w ~ RNP(NMeNMe),PNR (90)

P(NMeNMe),P

(9 1)

orientated POCCH coupling in the phosphate esters (92) had a maximum value of 2.7 Hz.l16 In vinyl phosphates (93) that cisoid POCCH coupling constant (maximum -2.8 Hz) was always larger than the transoid The PSCH couplingconstants of (94; Ch = 0 or S) were 14.1 and 15.8 H Z . ~ ~ 111

11* 11*

116

11'

W. G. Bentrude and H. W. Tan, J. Amer. Chem. SOC.,1973, 95, 4666. M. Revel and J. Navech, Bull. SOC.chim. France, 1973, 1195. E. E. Nifant'ev, A. A. Borisenko, and I. S. Nasonovskii, Mater. Vses. Kunf. Din. Stereokhim. ConformatsionnomuAnal., Ist, 70, 71, 112, (Chem. Abs., 1974, SO, 95 097). J. Durrieu, R. Kraemer, and J. Navech, Org. Magn. Resonance, 1973, 5 , 407. M. Bermann and J. R. Van Wazer, Inorg. Chem., 1974, 13, 737. R. H. Sarma, R. J. Mynott, D. J. Wood, and F. E. Hruska, J. Amer. Chem. SOC.,1973, 95, 6457.

236

Organophosphorus Chemistry 0

Relaxation Times,Paramagnetic Effects, and N.Q.R. Studies.-A study of the IsC n.m.r. spectra of the phosphetans (95) has shown that the tertiary carbon atoms have TI values of 0.6-4s whereas other carbon atoms have longer

Y (95)

relaxation times (8-18 s). Pseudo-equatorial methyl carbon atoms at C-2 and C-4 have shorter relaxation times than the corresponding pseudo-axial methyl g r 0 ~ p s . Variations l~~ of the effective distance between phosphorus atom and protons in adjacent molecules were calculated for tributyl phosphate from Tl values.l18Spin-rotation interactionshave also been calculated for a number of phosphorus halides.llg The 13Crelaxation times of lipids indicate that a fattyacid spin label stays in the vicinity of the phosphate groups.1zo N.q.r. parameters have been used to calculate the electronic properties of the nitrogen atoms in (96; Y = alkyl or halogen). The population of the electronpair orbital on nitrogen was at a minimum when Y = Br, and the population

.JOY Ch

Y2PNMe2

(96)

C JY -2P I-(

-

(97)

-

(981

of the PN 0-orbital was at a maximum when Y = F.121The W l n.q.r. spectra of (97) and (98) indicated that d,-p, interactions in the P-Cl bonds were small in the groundstate.la2The 36Cln.q.r. frequency and P- C1bond length of (99) have been compared with the data for compounds of the type (100) and chloropho~phazenes.~~~ Changes of the P-substituents over-ride the linear

11'

la1 la'

lSa

G. A. Gray and S. E. Cremer, J . Magn. Resonance, 1973, 12, 5. A. A. Vashman and I. S. Pronin, Zhur. strukt. Khim., 1972, 13, 1008. A. D. Jordan, R. G. Cavell, and R. B. Jordan, J. Chem. Phys., 1972, 56, 483; K. T. Gillen, ibid., p. 1573; N. I. Liu and J. Jonas, ibid., 1971, 55, 463. P. E. Godici and F. R. Landsberger, Biochemistry, 1974, 13, 362. D. Ya. Osokin, I. A. Safin, and I. A. Nuretdinov, Teur. i eksp. Khim., 1973, 9,404. V. V. Dorokhova, G. V. Ratovskii, Yu. K. Maksyutin, B. V. Timokhin, E. F. Grechkin, and G. K. Semin, Izuest. V.U.Z. Fiz., 1972, 15, 75. T. S. Cameron, C. Y. Cheng, T. Demir, K. D. Howlett, R. Keat, A. L. Porte, C. K. Prout, and R. A. Shaw, Angew. Chem. Internat. Edn., 1972, 11, 510.

237

Physical Methods

Ch

Ch

I1 II ChP-NR-PCh (99 1

(100)

relationship between bond length and n.q.r. frequency that has been found to exist for chlorophosphazenes. N.q.r. data have been reported for the compounds (101) 124 and (102).126A plot of n.q.r. frequencies of chloroarylphos-

(101)

(102)

phoranes (103) against the aggregate value of Hammett inductive constants indicated that the main transmission of inductive effect is born by the axial C1,P -NMe

I

I

Ar,PCI, -n

MeN -Pel,

(103)

(104)

chlorines and is about twice as great as that which occurs in the RaPCl series.12sN.q.r. data are also reported for the cyclic phosphorane (104).12’ Chemically induced dynamic nuclear polarization (CIDNP) has been used to study the mechanism of the reaction of radicals with dimethyl phosphite (105).12*The action of a t-butoxyl radical on tributyl phosphite (106; R = Bu) (MeO),PHO

(RO),P

(RO),kBd

C1,ChOE t),

Phi(OR),

(105)

(106 1

(107)

(108)

(109)

gave a negative polarization of the tributyl phosphate resonance, which is attributed to its formation from a pair of radicals one of which is the phosphorany1 radical (107).l2@Similar evidence indicated the intermediacy of (108) in E. A. Romanenko, Yu. P. Egorov, and P. P. Kornuta, Teor. i eksp. Khim., 1973,9,635. 0 . A. Raevskii, A. N. Vereshchagin, F. G. Khalitov, and E. N. Tsvetkov, Bull, Acad. Sci. U.S.S.R., 1973, 960. la@ I. P. Biryukov and A. Ya. Deich, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1918. A. D. Gordeev, E. S. Kozlov, and G. B. Soifer, Zhur. strukt. Khim., 1973, 14, 934. l B 8 Ya. A. Levin, A. V. Il’yasov, E. I. Goldfarb, and E. I. Vorkunova, Org. Magn. Resonance, 1973,5,487; D. G . Pobedimsky, P. A. Kirpichnikov, Yu. Yu. Samitov, and E. I. Goldfarb, ibid., p. 503. l a ( Ya. A. Levin, A. V. Il’yasov, and E. I. Goldfarb, Org. Magn. Resonance, 1973,5, 497.

l’4

lP6

238

Organophosphorus Chemistry

the photolysis of a mixture of triethyl phosphite and bromotrichloromethane, and the intermediacy of (109) in the reaction of phenyl radicals with trialkyl phosphites.l2 2 Electron Spin Resonance Spectroscopy

The e.s.r. spectra of y-irradiated phosphonyl dichlorides (1 10) in dilute solution indicated the formation of dimers, which may have structure (1 1l).130The

c1

ch

ch

II

PhPCL, (111)

(1 10)

y-irradiation of the phenylphosphinic acid (112) and the ylide (113) gave, in addition to (114), the less stable cyclohexadienyl radical (115). The 31Phyperfine couplings of (115) were similar to those of the radical (116), which

I' (1 12)

(1 13)

(114)

(115)

(1 16)

indicated strong hyperconjugation across the P- C bond.lsl The e.s.r. spectra of the radicals (117)13aand (118)133have been recorded. U.V.irradiation of R O ~ R

I1 0

(117)

PhfiPh

II

S (1 18)

trialkyl phosphate glasses gives a three-line spectrum corresponding to (119) after the decay of the alkyl r a d i ~ a 1 . lThe ~ ~ absence of splitting by the phosphorus atom in the hydrazyl radical (120) was attributed to a small contribuThe splitting for twelve phosphazo anion radicals (121) tion of the 3s 0rbita1.l~~ 0

II

*

R2PNNPh

S. P. Mishra and M. C. R. Symons, J.C.S. Dalton, 1973, 1494. S. P. Mishra and M. C. R. Symons, Tetrahedron Lerrers, 1973, 4061. la* C. M. L. Kerr, K. Webster, and F. Williams, Mol. Phys., 1973, 25, 1461. lS8 M. Geoffroy, Helv. Chim. Acta, 1973, 56, 1552. la' M. Sato, T. Katzu, Y. Fujita, and T. Kwan, Bull. Chem. SOC. Japan, 1973, 46, 2875. 186 F. G. Valitova, Yu. M. Ryzhmanov, and N. G. Gazetdinova, J. Gen. Chem. (U.S.S.R.), la0

lS1

1973,43, 1479.

239

Physical Methods

was minimal when Y = Z = Me,N. An increase in the number of electrondonating groups increased the 14Nsplitting constant of the nitro-group without affectingthe 31P~p1itting.l~~ MO calculationson the electron properties of

similar anion radicals gave hyperfine splittings in agreement with experimental r e s ~ 1 t s . lIt~ ~has been found that the electron in radicals (122) is localized on only one arylalkynyl The 31Phyperfine splitting in the spectrum of (123) was 81.4mT, which is close to that estimated for the

structure shown by extrapolating from the data for monoalkoxy (63 mT) and dialkoxy (70 mT) corn pound^.^^^ Some e.s.r. and CIDNP data are included in a review of phosphite and phosphine radical reactions.14*When phosphites possessing olefhic groups react with t-butoxyl radicals the initial spectrum of the phosphoranyl radical decays to give a new radical showing coupling to phosphorus and three protons, in accordance with the structure (124).141Very

Y-P,

c1 /Et

I

I .

Bu‘O (124)

(125)

large 31Phyperiine splittings (ca. 1000 G) and readily resolvable 36Cland splittings (ca. 40 G) are reported for (125; Y = Et or Cl).14aThe kinetics of the decay of PI1,PIII, and PIv phosphorus-centred radicals were measured at V. V. Pen’kovzkii, Yu. P. Egorov, I. N. Zhmurova, A. P. Martynyuk, and A. K. Shurubura, Teor. i eksp. Khim., 1973, 9, 112. lS7 Yu. P. Egorov, V. V. Pen’kovzkii, and B. N. Kuz’minzkii, Teor. i eksp. Khim., 1971, 7 , 601. la* S. P. Solodovnikov,A. I. Bokanov, L. I. Chekunina, and B. I. Stepanov, Bull. Acad. Sci. U.S.S.R., 1973, 215. la@ D. J. Whelm, Austral. J. Chem., 1973, 26, 1357. 140 D. G. Pobedimskii, N. A. Mukmeneva, and P. A. Kirpichnikov, Russ. Chem. Rev., 1972, 41, 555. 141 A. G. Davies, M. J. Parrott, and B. P. Roberts, J.C.S. Chem. Cornm., 1974, 27. 14* D. Griller and B. P. Roberts, J.C.S. Perkin 11, 1973, 1339. ls0

Organophosphorus Chemistry

240

-20 and -90 "C.143 It was concluded that the radicals undergo self-reactions at rates close to the diffusion-controlled limit. Pseudorotation of the spirophosphoranyl radical (126) using the unpaired electron as pivot gives an

(126)

identical configuration. If the odd electron had the properties of a proton, rapid pseudorotation would occur.However, the e.s.r. spectra of the phosphorany1 radicals indicate that pseudorotation is slow relative to the e.s.r. timescale. The e.s.r. spectrum of (126) is particularly revealing, for it shows separate triplet splittings of 3.3 and 1.0 G by two different pairs of hydrog e n ~The . ~ larger ~ ~ splitting is attributed to coupling to the apical protons cis to the odd electron, the smaller coupling to the radial protons cis to the odd electron, and zero coupling to all the trans-protons. The spectra of (127) and

(127)

(128)

(129 1

(128) show splittings of 4.0 and 3.5 G, respectively, each by one pair of hydrogens, i.e. the cis-apical protons (starred). The monocyclic radicals (129) showed splittings by one pair of hydrogens, i.e. the cis-protons (starred). The splitting is intermediate between those for apical and radial protons in (126), which is consistent with rapid pseudorotation. Note that retention of configuration in the radical oxidation of a cyclic phosphite implies that pseudorotation in the The intermediate (130) is slower than its rate of decomposition to e.s.r. spectrum of (131) rapidly changed from that of a phosphoranyl radical to one which possessed a small 31Psplitting (- 20 G),which indicates that the odd electron is localized on the aryl rings of one half of the molecule (relative to the e.s.r. time-scale) and that the two biphenylene groups are at right angles.146 D. Griller, B. P. Roberts, A. G. Davies, and K. U. Ingold, J. Amer. Chem. Soc., 1974, 96, 554. u4 D. Griller and B. P. Roberts, J. Organometallic Chem., 1972, 42, C47; J.C.S. Perkin II, 1973, 1416. l d b W. G . Bentrude, J. H. Hargis, and P. E. Rusek, Chein. Comm., 1969, 296. R. Rothuis, J. J. H. M. Font Freide, and H. M. Buck, Rec. Trau. chim., 1973,92, 1308.

14*

Physical Methods

241

E m . spectra have also been used to study the photolysis of spin-labelled natural phosphates 14' and charge-transfer reactions involving tris(dimethy1amino)phosphine14*and triphenylmethylphosphoniumsalts.149

3 Vibrational Spectroscopy The differing reports of the doublet or singlet nature of the PH, stretching bands of primary phosphines are probably due to a combination of the closeness in energy of the symmetric and asymmetric modes combined with slight broadening of the peaks by hydrogen-bonding. Thus although v(PH) of (132) appears as a singlet at 2286 cm-1,160the spectrum of trifluoromethylphosphine

(133) in the gas phase contains a doublet at 2339 and 2347 c 1 ~ 1 - l .Deuteriat~~~ ed (133) gave v(PD,) 1696 and 1705 cm-l.151 The intensity of the PC(a1iphatic) band for a series of phosphonium salts (134) decreased with increase in chain length of R. The band position and intensity were also dependent on the nature of the anion, appearing at 765 k 5 for the bromides and at 780k 10 cm-1 for the iodides.lS2The YQ8 (POP) band of (135) appears in the expected region of 951 cm-l, which leaves vsym (POP) as the only possible assignment for a strongly polarized band at 611 cm-1.163 The average frequency of the split v ( N C 0 ) bands of (136) coincides with the band position of the corresponding

1 . 7

141 14'

111

lSa

J. C. Seidel and J. Gergely, Arch. Biochem. Biophys., 1973, 158, 853; Y.Lion and A. Van de Vorst, Photochem. and Photobiol., 1973, 18, 169. G. Boekestein and H. M. Buck, Rec. Trav. chim., 1973, 92, 1095. Y. Suzuki and Y. Iida, Bull. Chem. Sac. Japan, 1973, 46, 2056. R. B. King, J. C. Cloyd, jun., and P. N. Kapoor, J.C.S. Perkin I, 1973, 2226. €3. Buerger, J. Cichon, R. Demuth, and J. Grobe, Spectrochim. Acra, 1973, 29A, 943. M. A. A. Beg, and Samiuzzaman, Pakistan J. Sci. Ind. Res., 1973, 16, 1. J. Emsley, T. B. Middleton, and J. K. Williams, J.C.S. Dalton, 1973, 2701.

242

Organophosphorus Chemistry

monoisocyanate~.~~~ A range of v(P= S) frequencies for thiophosphonic amides (137) have been reported and can be used to distinguish between S- and N-alkylated compounds.16S The change in frequency of v(PH) (3430247Ocm-l) and v ( N H ) for a number of spirophosphoranes (138) has been recorded for a wide range of 1.r. spectroscopy has also been used to study the isomerization of (139),lS7the dissociation of phosphonic acids,lSs the phosphonylation of cellulose,169and changes in the secondary structure of uridine derivatives.160 Stereochemical Aspects.-The barrier to inversion of phosphiran (140) has been estimated to be 33 kcal mol-l.lsl The Raman spectrum of gaseous tetramethylphosphine (141) contained a peak at 426 cm-l, which disappeared on

/cF

CH2-PH (140)

solidification and was therefore assigned to a gauche conformer.16a The intensity of the band indicated that 60 % of the molecules had a gauche conformation. The vibrational spectra of (142) correspond to a trigonal-pyramidal molecule. There was no evidence of hindered rotation of the trifluoromethyl Chlorophosphinesand chlorophosphiteshave attracted the attention

(142)

(1431

(144)

(145)

of many workers. Conformational analysis of alkyl- and dialkyl-chlorophosphines (143),la4,lBS thioesters (144),ls6 and of the cyclic phosphites (145; Yu. P. Egorov, A. A. Kisilenko, and V. A. Shokol, Teor. i eksp. Khim., 1973,9, 813, J. Boedeker, J. Organometallic Chem., 1973, 56, 255. Iko M. Barthelat, B. Garrigues, and R. Mathis, Compt. rend., 1973, 277, C,415. B. A. Arbuzov, A. 0. Vizel, R. R. Shagidullin, R. S. Giniyatullin, L.I. Shchukina, and L. Kh. Ashrafullina, Doklady. Akad. Nauk. S.S.S.R., 1973, 209, 349. la@ B. V. Zhadanov, A. M. Lukin, N. A. Bolotina, I. A. Polyakova, and G. B. Zavarikhina, Doklady. Akad. Nauk. S.S.S.R., 1973, 208, 124; A. Yu. Kireeva, B. V. Zhadanov, B. I. Bikhman, and N. M. Dyaltona, Tr. Vses. Nauch.-Issled. Inst. Khim. Reaktivov Osobo Chist. Khim. Veschesty, 1972, 12, (Chem. Abs., 1974, 80, 95 039). l * * M. M. Sadykov, A. A. Adylov, A. Yuldashev, and Yu. T. Tachpulatov, Vysokomol. Soedineniya, 1972, 14, B, 196. loo V. M. Lobachev, E. I. Sukhorukov, and N. M. Gusenkova, Siojkika, 1973,18, 586. J. Bragin and L. W. Dennis, J. Mol. Structure, 1973, 18, 75. 18* J. R. Durig and R. W. MacNamee, J. Mol. Structure, 1973, 17,426. D. H. Lemmon and J. A. Jackson, Spectrochim. Acta, 1973, 29A, 1899. A. B. Remizov, I. Ya. Kuramshin, and A. I. Fishman, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1393. I. Ya. Kuramshin, E. A. Ishmaeva, A. A. Muratova, and A. N. Pudovik, Doklady. Akad. Nauk S.S.S.R., 1974,214, 349. 164

243

Physical Methods

it = 1 and 2 ) l G G lG $ have 7 been completed. The spectrum of the last compound ~~ indicated that the chlorine atom occupies an equatorial p 0 ~ i t i o n . lSimple group-frequency correlations cannot be made for all the bonds of the triAuoromethylphosphines (146; Y = CF,, Hal, or H) owing to substantial

S 0

F,C ‘P-Hal

Y/

(146)

II

II

Ch

RPCH C1

I1

I

R,PCH,CN

Me,PChMe

CI

(147)

(148)

(149)

mixing of the co-ordinates of vibration.168The conformations of a number of phosphine oxides (147),IG9(lO2),lZ5phosphinates (148; Ch = 0 or 171 and (149)172have also been studied by i.r. spectroscopy, sometimes in combination with dipole measurements. The vibrational spectra of (150) 173 and S),1709

ClCH, Po,Na, (150)

But,PF, (15 1)

(151) 17*were in best accordance with Cssymmetry; for the latter compounds preference was given to a trigonal bipyramid (tbp) with radial t-butyl groups.174 Studies of Bonding.--p,-p, Bonding in aryl PIII compounds (152)175and (153)17G and their corresponding oxides has been studied through their aryl

A. B. Rcniizov, R. I. Kozlova, N. N. Vaklirusheva, and T. G. Mannafov, Zhur. priklad. Spektroskopii, 1973, 19, 109. l e 7 A. B. Remizov, R. R. Shagidullin, D. F. Fazliev, and T. G. Mannafov, Optika Spectroskopiya, 1973, 34, 252. 16* J. D. Brown, R. C . Dobbie, and B. P. Straughan, J.C.S. Dalton, 1973, 1691; R. C. Dobbie and B. P. Straughan, J.C.S. Dalton, 1973, 2754. l a D 0. A. Raevskii, Yu. A. Donskaya, F. G . Khalitov, and L. A. Antokhina, Bull. Acad. Sci. U.S.S.R., 1973, 1293. 1 7 0 A. B. Remizov, E. G. Yarkova, I. Ya. Kuramshin, and A. A. Muratova, Zhur. priklad. Spektroskopii, 1973, 18, 491. I 7 l A. B. Remizov, 1. Ya. Kuramshin, A. V. Aganova, and G. G. Butenko, Doklady. Akad. Nauk S.S.S.R., 1973, 208, 1118. 1 7 8 0. A. Raevskii, F. G. Khalitov, Yu. A. Donskaya, and I. M. Shermergorn, Bull. Acad. Sci. U.S.S.R., 1973, 774. 1 7 ? G. Brun and G. Jourdan, Compt. rend., 1973, 277, C , 507. 1 7 4 R. R. Holmes, G. T. K. Fey, and R. H. Larkin, Irzorg. Chem., 1973, 12, 2225. 1 7 5 V. V. Dorokhova, G. V. Ratovskii, B. V. Timokhin, E. F. Grechkin, and A. V. Kalabina, Izvest. V.U.Z. Fiz., 1972, 15, 25; R. €2. Shagidullin and A. V. Chevnova, Bull. Acad. Sci. U.S.S.R., 1912, 693. 1 7 e 0. A. Yakutina, G. V. Ratovskii, Yu. L. Frolov, L. M. Sergienko, and V. G . Rozinov, Teor. i eksp. Khim., 1971, 7, 514.

9

244

Organophosphorus Chemistry

frequencies and integral intensities J* of the Raman lines. Carbonyl frequencies were used in similar studies of acyl phosphines (154) and their PIv Force constants have been evaluated for the diphosphine (155),178 the dithiophosphinates (156),170 the isocyanate (157),lao the phos0

Y zps;

II C1,PNCO

Ch

Ch

II MeP ( S Me

)2

II

Me,PSMe

phazene (101),ls1and the thio-esters (158) and (159).lS2 In the thio-esters, P and M ~ P S M were ~ nearly constant but ~ P = Oand ~P,S increased as Me replaced SMe.lS2 An i.r. and n.m.r. study of Y-substituent effects in (160)

~

(160)

revealed large shifts of v[CC(Ar)] to low frequency for the halogen derivatives. MO calculations indicated that the halogen atom was more strongly nconjugated to the aryl ring than the carbonyl group, and that when both groups are present the carbonyl group may be rotated out of Hydrogen-bonding studies of organophosphorus compounds continue to be of wide interest. The absence of shifts of v(PH) for phosphiran upon condensation to the solid ruled out the presence of hydrogen-bonding.161The electron-donor capacities of phosphine oxides (161) have been compared with those of s ~ l p h o x i d e s Studies . ~ ~ ~ of the phosphine sulphide-phenol mixtures showed that hydrogen-bonded complexes are formed, the enthalpy of formation increasing with the number of P-alkyl groups.185It has been found that + p a

+Ich.'.'f

(RO),P,

R,$-eh.. (161) 177 170

179

180 181

lan laS

-.HOY

--y

(RO) P\c/ 0

O ,

CR2 (162)

'eM

'C(N,)CO,R (163)

T. Osaki, J. Otera, and Y. Kawasaki, Bull. Chem. SOC.Japan, 1973, 46, 1803. H. Buerger, J. Cichon, R. Demuth, J. Grobe, and F. Hoefler, 2. anorg. Chem., 1973, 396, 199. H. W. Roesky, R. Pantzer, and J. Goubeau, Z . anorg. Chem., 1972, 392, 42. Yu. P. Egorov, A. A. Kisilenko, and V. A. Shokol, Zhiir. strukt. Khim., 1973, 14, 240. E. A. Rornanenko, Yu. P. Egorov, and P. P. Kornuta, Spectroscopy Letters, 1973, 6, 363. R. Pantzer, W.Schmidt, and J. Goubeau, 2. anorg. Chem., 1973, 395, 262. V. M.D'Yakov, M. G. Voronkov, and V. F. Sidorkin, J. Gen. Chem. (U.S.S.R.),1973, 43, 1520. S. M. Petrov and V. S. Pilyugin, Zhur. priklad. Spektroskopii, 1972, 17, 541. R. R. Shagiddin, I. P. Lipatova, L. I. Vachugova, and S. A. Sarnartseva, Doklady. Akad. Nauk S.S.S.R.,1972, 202, 617.

PhysicaI Metlzods

245

the shift of v(0H) of intramolecularly hydrogen-bonded compounds is greater for the sulphide (162; Ch = S) than for the oxide (162; Ch = 0). The difference was attributed to the larger sulphur atom.las Studies of the 8-diazo-phosphonate (163) showed that the intensities of the OH band at 3220-3250 cm-1 decrease upon dissolution and then dilution, whilst a new band at 3390-3400 cm-1 intensifies. The bands were assigned to inter- and intra-molecularly hydrogen-bonded OH, respectively.f1oA number of ketoenol equilibria have been studied. It was concluded that the lower frequency band of (164) at 2700 cm-I was also due to intermolecular hydrogen-bonding, 0

(166)

(165)

(164)

in this case involving the trans-enol (165).lS7 The trans-enol had v(C=C) 1630 cm-1 whilst the cis-enol had v(C=C) 1600 and v(0H) 3100 crn-l, the latter band also being attributed to an intermolecularly hydrogen-bonded species.187The aldo-form (164; R = Me) and the keto-form (166)la8 were observed only in solution. In fact for (164; R = H) lag and the corresponding phenylphosphonatel D O the aldo-form predominated in solution. The enolic forms of (167) were considered to have their OH groups intermolecularly hydrogen-bonded to anions.6 2 Intramolecular hydrogen-bonding was present

.Ph,PCH + /mMe

‘COR

Ph, P=CH-

C -CAr

//

0

H-0

\\

Y

in the ylide (168) and its salt.lgl The shifts of the v(0H) bands of (169) could be correlated with Y substituent constants,1g2but neither v(P0C) nor v ( P 0 ) gave R. R. Shagidullin, N. I. Rizpolozhenskii, F. S. Mukhametov, I. P. Lipatova, and L. I. Vachugova, Bull. Acud. Sci. U.S.S.R., 1972, 2728. l n 7 E. 1. Matrosov, S. T. Ioffe, and M. I. Kabachnik, J. Gen. Chem. (U.S.S.R.), 1972, 42, 2617.

T. A. Mastryukova, Kh. A. Suerbaev, P. V. Petrovskii, E. I. Matrosov, and M. I. Kabachnik, Zhur. obslzchei Khim., 1972, 42, 2620. l S 9 A. I. Razumov, G. A. Savicheva, T. V. Zykova, M. P. Sokolov, B. G. Liorber, and R. A. Salakhutdinov, Zhur. obshchei Khim., 1971, 41, 1954. l S 0 A. I. Razumov, G. A. Savicheva, T. V. Zykova, M. P. Sokolov, G. G. Smirnova, B. G. Liorber. and R. A. Salakhutdinov, J. Gen. Chem. (U.S.S.R.), 1971, 41, 2189. I e 1 M. I. Shevchuk, M. V. Khalaturnik, and A. V. Dombrovskii, J. Gen. Chem. (U.S.S.R.),

lSs

1972, 42, 2621. lB2

R. R. Shagiduflin, A. V. Chernova, F. S. Mukhametov, and N. I. Rizpolozhenskii, Izvest. Akad. Nauk S.S.S.R., Sei.. khim., 1972, 2585.

246

Organophosphorus Chemistry

satisfactory relationships with the rate constants of the hydrolysis of orthophosphate m o n o e ~ t e r s .Further ~~ reports have appeared on the effects of phosphonium salts on hydrogen bonding in 4 Microwave Spectroscopy

The microwave spectra of phosphine l g 4 and methyldifluorophosphine (170) l g 5have been recorded. The dipole moment, the P-C bond length, and the barrier to methyl rotation of (170) were estimated to be 2.056 D, 182 pm, CH,PF,

(1 70)

and 2.3 kcal mol-l, respectively. The borane adducts of phosphine l g 6and (170)la7have also been studied, and the barrier to internal rotation has been estimated in the former case.lg6 5 Electronic Spectroscopy Absorption.-Interest in the conjugation effects of aryl PIr1compounds is still keen. The large intensifications and shifts to longer wavelengths of the benzenoid bands that are characteristic of anilines, phenolic compounds, and aryl thiols and sulphides, are much weaker in the U.V. spectra of monoarylphosphines. The interaction of the phosphino-group is sufficiently weak that second substituents are liable to dominate the spectra and obliterate any arylphosphine chromophoric properties.18c Also, recent work on the PE spectrum of an arylphosphine (see below) has shown that there is very little interaction in the ground state. However, the bathochromic shift of the main band of arylphosphines upon increasing the number of aryl rings,175the effect of para-substituents on the spectra of arylphosphines (1 53), (1 71), and their

corresponding oxides,lgsand the transformation of the spectrum of triphenylphosphine, upon complexation, to that of benzene,lg9have all been used as evidence for the existence of pA-pnconjugation, at least in the excited state of P. R. Philip and C. Jolicoeur, J . Phys. Chem., 1973, 77, 3071; E. V. Ryl'tzev, I. E. Boldeskul, A. F. Pavlenko, Yu. P. Egorov, and V. P. Akkerman, Zhur. priklad. Spektroskopii, 1972, 16, 513. lo' F. Y.Chu and T. Oka, J. MoZ. Spectroscopy, 1973, 48, 612. lS6 E. G. Codding, R. A. Creswell, and R. H. Schwendeman, Znorg. Chem., 1974, 13, 856. J. R. Sabin, Chem. Phys. Letrers, 1973, 20, 212. l o ' R. A. Elzaro, Dim. Abs. Znternat. ( B ) , 1973, 34, 1052. lS8 V. V. Dorokhova, G. V. Ratovskii, B. V. Timokhin, G. A. Pensionerova, and E. F. Grechkin, Izuest. V.U.Z. Fiz., 1973, 16, 31. l a BI. P. Romm, E. M. Sadykova, E. N. Gur'yanova, and I. D. Kolli, J. Gen. Chem. (U.S.S.R.), 1973, 43, 727. lea

247

Physical Methods

aryl PIr1 compounds. Calculated n-overlap integrals also supported p n overlap, and heats of complexation have indicated that the conjugation in triarylphosphines is of a similar order to that in sulphur corn pound^.^^^ Calculations of the electronic structures of the triphenyl derivatives of Group VB elements have been completed.200Conjugation in acylphosphines (154) and some of their PIv derivatives was investigated using the carbonyl n+n* bands1'' Studies of the spectra of a range of sulphides (172),201the isocyanates (173;

(172)

(173)

(1 74)

Y = Me or C1),202and styryl and vinyl ethers (174)203have been reported. Further studies of N-arylphosphinimines (175) have shown that, although changes in Y have little effect on the U.V. spectrum, they greatly affect the pKa.'04 When one of the aryl groups which are bonded to phosphorus is

(1 76)

(175) 4-

replaced by the phosphinimine group Ar,PN, as occurs in (176), the bands appear at much longer wavelength. It has also been found that an increase in the donor properties of the aryl rings of the phosphinimine group has an auxochromic effect on the spectra of (176).205 The correlation of the absorption maxima of (175; Y = H) with Hammett substituent constants of Z has also been studied.206 The bathochromic effects of intramolecular hydrogenbonding on the 260 and 390 nm bands of (163) are reported.ll*

201

aoa

eo4

t06

lo' 208 *OS

210

N. P. Borisova, L. N. Petrov, and N. S. Voronovich, Spektrosk., Tr. Sib.Soueshch., dth, 68, 1973, 198. V. V. Dorokhova, G. V. Ratovskii, N. A. Sukhorukova, and E. F. Grechkin, Izuest. V.U.Z. Fiz., 1973, 16, 150. Yu. P. Egorov, A. A. Kisilenko, and V. V. Pen'kovskii, Teor. i eksp. Khim., 1972,8,612. V. V. Dorokhova, G. V. Ratovskii, V. E. Kolbina, E. F. Grechkin, and A. V. Kalabina, J. Gew. Chem. (U.S.S.R.), 1973, 43, 2164. 1. N. Zhmurova, V. G. Yurchenko, V. P. Kakhar, and L. A. Zolotareva, J . Gen. Chem. (U.S.S.R.), 1972, 42, 2646. I. N. Zhmurova, R. I. Yurchenko, and A. P. Martynyuk, J. Gen. Chem. (U.S.S.R.), 1973, 43, 1032; T. G. Edel'man and B. I. Stepanov, ibid., p. 554. I. N. Zhmurova, R. I. Yurchenko, V. G. Yurchenko, and A. A. Tukhar', J. Gen. Chem. (U.S.S.R.), 1973, 43, 1028. W. Schafer and A. Schweig, Angew. Chem. Internat. Edn., 1972, 11, 836. H. Bock, G. Wagner, and J. Kroner, Tetrahedron Letters, 1971, 3713. P. Baybutt, M. F. Guest, and I. H. Hillier, Mol. Phys., 1973, 25, 1025. W. Schafer, A. Schweig, F. Bickelhaupt, and H. Vermeer, Angew. Chem. Internat. Edn., 1972, 11, 924.

248

Organophosphorus Chemistry

Photoelectron.-The photoelectron (PE) spectrum of (177) is similar to the added spectra of benzene and trimethylphosphine, which indicates that there

(177)

is little interaction between the dimethylphosphino-group and phenyl ring in the ground This is in contrast to the situation in dimeth~laniline,~~~ anisole, and thioanisole.208The limitations of using MO methods to predict orbital ordering of phosphines have been The phosphorin (178) and pyridine PE spectra are also quite different.l*C Unambiguous proof that, in

But

6

MeO’

p/ But ‘OMe

(180)

contrast to pyridine, the phosphorin br (n)MO (179) is occupied (has a low total energy) before the a,(n) MO (180) has been obtained from the PE spectra of the anthracene derivatives.210The PE spectrum of (181) has been compared with that of the tris-t-butyl derivative of (178).211One of the MO’s is raised in energy by interacting with the lone pairs of electrons on oxygen, which are orientated above the plane of the aryl ring. Similar studies have been completed on phosphanaphthalene derivatives.212 The 2p electron energies of phosphorus of triphenylphosphine, methyltriphenylphosphonium bromide, and (66) were 127.6,130.5, and 129.2 eV. These data and the P-C bond lengths were used to estimate the amount of ylide character of (66).21sThe relationship of the binding energies of 2p electrons with the effective charge on phosphorus has been determined.214Reports have also appeared on the PE spectra of TCNQ-phosphine complexes216 and pentafluorophosphorane. In the spectrum of the latter compound one of the bands exhibited fine structure, corresponding to PF2 stretching of the apical bonds, which indicates the involvement of a c-bonding orbital.216 Fluorescence.-A preliminary study has been made on elemental phosphorus. 217 A. Schweig, W. Schafer, and K. Dimroth, Angew. Chem. Internat. Edn., 1972, 11, 631. W. Schafer, A. Schweig, G . Maerkl, and K. H. Gottfried, Tetrahedron Letters, 1973, 3743. sla H. L. Ammon, G . L. Wheeler, and P. H. Watts, J. Amer. Chem. SOC.,1973, 95, 6158. L. Maijs, L a t u . P.S.R. Zinat. Acad. Vestis., Khim Ser., 1973, 394. l l 8 I. Ikemoto, J. M. Thomas, and H. Kuroda, Faraday Discuss. Chem. SOC.,1972,54, 208. *la D. W. Goodman, M. J. S. Dewar, J. R. Schweiger, and A. H. Cowley, Chem. Phys. Letters, 1973, 21, 474. *17 T. Kariya and Y. Noguti, Kochi Daigaku Gakujutsu Kenkyu Hokoku Shizen Kagakic, 1972, 21, 295. *l2

Physical Methods

249

Simultaneous determination of ATP and NADPH by fluorescence spectromol 1-1.21s scopy is reported to be sensitive to

6 Rotation and Refraction Physicochemical studies, which include magneto-optical studies, have been reported for a series of diethylamino-compounds (1 82) 219 and alkylfluorophosphoranes (1 83). 220 It is concluded that the electronegativity of the neutral Pv atom (x" 2.8) is slightly greater than that of the neutral PIIr atom (x" 2.1)

and that the Pv atom possesses unambiguous n character.220The magnetooptical rotation of the cyclotriphosphazenes (184) increased linearly with an increase in the number of P-amino-groups. It also depended on the orientation of the groups, decreasing in the order trans > cis > geminal.221The electronic structures of cyclotriphosphazenes and phosphadiazenes have been studied by EHMO calculations.222 The phosphonate (185) was resolved using dibenzoyld-tartaric acid.223

7 Diffraction X-Ray.-There has been an increase in the number of X-ray diffraction studies. The molecular structures of the phosphadiazole (186),224the phosphole (1 87),225and the aminophenylphosphine(188) 22* have been determined.

2aa

A. B. Makarov and V. A. Protashchik, Fiziol. Rast., 1973, 20, 646. Y. Coustures, M. C. Labarre, and M.F. Bruniquel, Bull. SOC.chim. France, 1973, 926. M. Hausard, M. C . Labarre, and D. Voigt, J. Fluorine Chem., 1973, 3, 375. M. F. Bruniquel, J. P. Faucher, J. F. Labarre, M. Hasan, S. S. Krishnamurthy, R. A. Shaw, and M. Woods, Phosphorus, 1973, 3, 83. V. V. Pen'kovskii, Yu. P. Egorov, and D. P. Khomenko, Teor. i eksp. Khim., 1973, 9,

2sa

445. S. V. Rogozhin, V. A. Davankov, and Yu. P. Belov, Bull. Acad. Sci., U.S.S.R., 1973,

'lS 2po lal

pz4

aa6

azs

926. V. G. Andrianov, Yu. I. Struchkov, N. I. Shvetsov-Shipvskii, N. P. Ignatova, R. G. Babkova, and N. N. Mol'nikov, Doklady. Akad. Nauk S.S.S.R., 1973,211, 1101. P. Coggon and A. T. McPhail, J.C.S. Dalton, 1973, 1888. W. Dreissig and K. Plieth, 2. Krist., 1972, 135,294.

250

Organophosphorus Chemistry

The short N-C(Ph) bond (138 pm) found for (188) indicated partial doublebond character owing to electron donation by the amino-group. The conformations of triphenylphosphine in the free and solid states 2 2 7 and the nitrile tilt angle for (189) 228 have been calculated. The five-membered ring of (190) has been found to be significantly n ~ n - p l a n a rCrystal . ~ ~ ~ and molecular structures of the ylides (191),230(192),231and (181) 213 have been determined. The

(192)

PCC and CCC bond angles (126.6 and 127.7') involving the a- and P-carbon atoms of the ally1 group of (191) are considerably increased compared to sp2 angles.23oIt has been concluded that the ylide character cannot be estimated from the P-C bond length on the basis of complete ylene structure for methylenetriphenylph~sphorane.~~~ Studies are also reported for the iminophosphorane (193),232(194),233monoclinic triphenylphosphine oxide,2 3 4 the Ph,iNSO, eQ . 1193)

Ph,iMe (TCNQ);

(194)

'X

OS 'kh,

(195)

tritolylphosyhine s ~ l p h i d e s ,and ~ ~ ~other para-substituted triarylphosphine sulphides (195).236The X-ray diffraction results of the extractants (196) have been reviewed. 2 3 7 The molecular structure of diphenylphosphinic acid 2 3 8 and aa7

2so

s31

p32

*36

lS7

*sB

C. P. Brock and J. M. Ibers, Acta Cryst., 1973, B29, 2426. C. Leibovici, J. Mol. Structure, 1973, 18, 343. H. P. Calhoun, M. R. LeGeyt, and N. L. Paddock, J.C.S. Chem. Comm., 1973, 623. B. L. Barnett and C. Krueger, Cryst. Struct. Comm., 1973, 2, 427. M. A. Howells, R. D. Howells, N. C. Baenziger, and D. J. Burton, J. Amer. Chem. SOC., 1973, 95, 5366. A. F. Cameron, N. J. Hair, and D. G. Morris, Acra Cryst., 1974, B30, 221. M. Konno and Y. Saito, Acta Cryst., 1973, B29, 2815. A. I. Gusev, N. G. Bokii, N. N. Afonina, T. V. Timofeeva, A. E. Kalinin, and Yu. T. Struchkov, Zhur. strukt. Khim., 1973, 14, 116. T. S. Cameron, K. D. Howlett, R. A. Shaw, and M. Woods, Phosphorus, 1973, 3, 71. W. Dreissig and K. Plieth, Acta Cryst., 1972, B28, 3478; W. Dreissig, K. Plieth, and P. Zaeske, ibid., p. 3473. A. V. Nikolaev, L. N. Mazalov, E. A. Gal'tsova, and A. P. Sadovskii, Zzvest. sibirsk. Otdel. Akad. Nauk S.S.S.R., Ser. khim. Nauk, 1972, 72, 7 . D. Fenske, R. Mattes, J. Loens, and K. F. Tebbe, Chem. Ber., 1973, 106, 1139.

251

Physical Methods

the cyclic phosphonic acid (197) lo6have been determined. The five-membered ring of (197) is essentially planar, which distorts the bond angles to phosphorus. The P - 0 bond lengths for the two exo-oxygensare identical (151 pm),

(RO), R,-,m (196)

(197)

suggestingthat the acidic proton is intramolecularlyhydrogen-bonded equally to both atoms. Several other cyclic phosphonyl compounds have been studied the thioamide (198), 239 the cyclic thiophosphonic anhydride (1 99) (which has a planar heterocyclicring, probably owing to repulsions between the phosphorus

(199)

(198)

(200)

s u b s t i t ~ e n t s )and , ~ ~the ~ cyclic ester (200), which possesses a hydrogen-bonded PH The cyclic phosphate (201) possesses an axial phenoxy-group trans to the axial chloromethyl Both of these groups have shown a OPh

(20 1)

(202 1

preference to occupy the axial position. In the isomer of (201) it is the phenoxygroup that dominates the axial position, forcing the chloromethyl group into an equatorial orientation.242b The crystal structures have been reported of several biologically involved phosphates,243 the cancer drug cyclophosphamide 239 ppO

4pa

G.J. Bullen, J. S . Rutherford, and P. A. Tucker, Acta Cryst., 1973, B29, 1439. J. J. Daly, L. Maier, and F. Sanz, Helv. Chim. Acta, 1972, 55, 1991. W. Saenger and M. Mikolajczyk, Chem. Ber., 1973, 106, 3519. (a) P. Wagner, W. Jensen, W. Wadsworth, and Q. Johnson, Cryst. Struct. Comm., 1973,2,507; (b) W. Wadsworth, J. Org. Chem., 1973,38,256; R. Wagner, W. Jensen, W. Wadsworth, and Q. Johnson, Cryst. Struct. Comm., 1973, 2, 327. A. K. Chwang and M. Sundaralingam, Nature New Biol., 1973, 244, 136; D. Suck, P. C. Manor, G. Germain, and C. H. Schwalbe, Nature New Biol., 1973, 246, 161; A. R. Hagen, Acta Odontol. Scand., 1973, 31, 149.

252

Organophosphorus Chemistry

(202),244and its keto-deri~ative.~~~ The molecular structures of a triphosp h a ~ e n e a, ~tetraphosphazene, ~~ 2 4 7 and the triphosphaborane (203) 2 4 8 have been determined. The latter compound had a chair conformation and P-B

(203)

(204)

bond lengths compatible with o-bonds. The combination of four- and fivemembered rings in the cyclic phosphorane (204; Y = CF,) was shown to produce square-pyramidal geometry.2 4 9 Another phosphorane, the adamantane derivative (205), had a distorted tbp geometry.z50An X-ray study of the

(205 1

(206)

pyrroletetrafluorophosphorane(206) revealed a fairly short PC bond (173 pm ; cf. 178pm for MePF,), in accordance with the considerable n-donating properties of the pyrrole ring.a51 Electron.-The electron-diffractionspectrum of phenyldichlorophosphine is in agreement with damped The gulch method of non-local search of the minima of a many-variable function has been used to find preliminary models for (207).253CNDO/2 calculations of the conformations of the difluorophosphine (208) 264 corresponded to the X-ray results. Studies have been reported on trifluorosilylphosphine265 and the cyclic phosphites (209; *‘$

S. Garcia-Blanco and A. Perales, Acta Cryst., 1972, B28,2647. N. Camerman and A. Camerman, J. Amer. Chem. Soc., 1973, 95, 5038. H. R. Allcock and M. T. Stein, J. Amer. Chem. Sot., 1974, 96, 49. G . J. Bullen and P. E. Dann, J.C.S. Dalton, 1973, 1453. G . J. Bullen and P. R. Mallinson, J.C.S. Dalton, 1973, 1295. J. A. Howard, D. R. Russell, and S. Trippett, J.C.S. Chem. Comm., 1973, 856. W. C. Hamilton, J. S. Ricci, F. Ramirez, L. Kramer, and P. Stern, J. Amer. Chem. Soc., 1973,95, 6335.

W. S. Sheldrick, J.C.S. Dalton, 1973, 2301. B b a V. A. Naumov, N. M. Zaripov, and N. A. Gulyaeva, Zhur. strukt. Khim., 1972,13,917 a68 N . M. Zaripov, V. A. Naumov, and L. L. Tuzova, Acta Cryst., 1973, B29, 2186. *b4 M. C. Bach, C. Brian, F. Crasnier, and J. F. Labarre, J. Mot. Structure, 1973, 17, 23. l S 6 R. Demuth and H. Oberhammer, 2. Naturforsch., 1973, 28a, 1862. lbl

253

Physical Methods

I

c1 (21 1)

n = 1 or 2),256s 2 5 7 the chlorophospholen (210),267 and the chlorophosphates (21 1 ; Ch = 0 or S).268 The phosphates were in half-chair conformations. Data for the catechol derivative (212) were compared with those for a related methyl ester. 2 5 9 The trimethyl phosphate spectrum corresponded to two

(212)

(213)

conformers with C, symmetry, present in a ratio of 3 : 1. 260 The spectrum of the isocyanate (213) indicated that it had the trans conformation shown, with a slightly lengthened P-Cl bond (200.6 pm).261 8 Dipole Moments, Conductance, and Polarography A method of evaluating dipole moments has been devised which takes into account d,-p,, contributions.2 6 2 The decrease in dipole moment which occurs when ortho methyl groups are present in triarylphosphines,e.g. (214), indicates

pK@

367

268

2SD

V. A. Naumov and N. M. Zaripov, Zhur. strukt. Khim, 1972, 13, 768; N . M. Zaripov and V. A, Naumov, ibid., 1973, 14, 588. V. A. Naumov, N. M. Zaripov, and V. N. Semashko, Mater. Nauch. Konf. Znst. Org. Fiz. Khim. Akad. Nauk S.S.S.R.,1969, 78. V. A. Naumov, V. N. Semashko, A. P. Zav’yalov, R. H. Cherkasov, and L. N. Grishina, Zhur. strukt. Khim., 1973, 14, 787. V. A. Naumov and S. A. Shaidulin, Zhur. strukt. Khim., 1974, 15, 133. H. Oberhammer, 2. Naturforsch., 1973, 28a, 1140.

V. A. Naumov, V. N. Semashko, and L. F. Shatrukov, Doklady Akad. Nauk. S.S.S.R., 1973, 209, 118. A. S. Tarasevich and Yu. P. Egorov, Teor. i eksp. Khim., 1971, 7 , 747.

254

Organophosphorus Chemistry

considerable changes in geometry.2 6 3 A comparison of measured and calculated dipole moments indicates that the changes are due to increases in CPC bond angles and d,-p, bonding.264Dipole moments have been used in conjunction with i.r. spectroscopy to study conformational preferences of thioesters (215),165(148),171 and (149).172Dipole moments of a number of

RSP,

/y Z

(215)

F (216)

halogenophosphorus compounds have been measured,2 6 5 and for difluorocyanophosphine (216) the data indicated a non-linear PCN group owing to interactions of the phosphorus 3p electrons with the cyano-group.2 6 6 Studies of the cyclic amide (217; Y = NMe,) indicated that the PN bond moment is directed towards the nitrogen atom 287 and that (217;Y = Cl) has the chlorine in an equatorial position.268The PC bond moments changed from 0.4 D for

the dichloro-compounds (218 ;Ch = 0)to only 0.09 D for (218 ;Ch = S) ;2 6 the dipole moments of the corresponding diethyl- and diethoxy-vinyl compounds were also determined.2 6 9 Graphical treatment of dipole moments and Kerr constants showed that the ring of (219; Y = OR) is bent 140 to 165"and that the alkoxy-group is p s e ~ d o - a x i a l Studies . ~ ~ ~ of the halogeno-derivatives (219; Y = F or CI) were more complicated, and mixtures of conformers may be Kerr constants were also used in a study of (220) z 7 2 and (102).125 a6s

I. P. Romm, N. A. Romanel'skaya, E. N. Gur'yanova, A. I. Bokanov, and B. I. Stepanov, J. Gen. Chem. (U.S.S.R.),1973, 43, 1633. I. P. Romm, E. N. Gur'yanova, and K. A. Kocheshkov, Doklady Akad. Nauk S.S.S. R., 1973, 212, 112.

a@6

*06

*W

Yu. P. Egorov, V. I. Katolichenko, and U. Y. Borovikov, Teor. i eksp. Khim., 1972, 8, 761; R. G. Hyde, J. B. Peel, and K. Terauds, J.C.S. Faraday ZI, 1973, 69, 1563. W. R. Hall and H. F. Hameka, Inorg. Chem., 1973,12, 1878. E. E. Nifant'ev, I. S. Nasonovzkii, and A. A. Kryuchkov, Zhur. obshchei Khim., 1973, 43, 71.

B. A. Arbuzov, R. P. Arshinova, A. N. Vereshchagin, S. G. Vul'fson, 0. N. Nuretdinova, and L. 2.Nikonova, Khim. geterotsikl. Soedinenii, 1971, 7, 1324. E. A. Ishmaeva, G. A. Kutyrev, and A. N. Pudovik, J. Gen. Chem. (U.S.S.R.),1973,43, 2315.

B. A. Arbuzov, R. P. Arshinova, A. N. Vereshchagin, and S. G. Vul'Fson, Bull. Acad. Sci. U.S.S.R.,1973, 1913. R. P. Arshinova, A. N. Vereshchagin, and S. G. Vul'fson, Bull. Acad. Sci. U.S.S.R., 1973, 2185.

A. N. Vereshchagin, R. P. Arshinova, S. G. Vul'fson, R. A. Cherkasov, and V. V. Ovchinnikov, Khim. geterotsikl. Soedinenii, 1971, 7 , 1464.

255

Physical Methods

The endo PS bond moment in (221 ;X = C1) was estimated to be 0.58 D and directed from sulphur to The dipole moments of fourteen enol

f'l o,

0,

R S : p

YP\Y

/s 'x

S

(220)

(22 1)

phosphates were all about 3 D and did not agree with moments calculated by CND0/2. Better correlations were obtained using parameters proposed by D. P. Santry for the phosphorus atom.274 The polarographic reduction of triphenylphosphine oxide and trioctylphosphine oxide at low concentration in nitroethane has been The estimation of phosphate insecticides by polarography has been reported,27s and the rearrangement of a-hydroxyphosphinates has been followed by conductance.277 9 Mass Spectrometry In general, cleavage of P- C bonds of organophosphorus compounds occurs fairly readily upon electron bombardment, even to the extent that the 2phosphanaphthalene (222) gives an M-PH ion which is the second most abundant ion (94 % R.A.) in the spectrum.2 7 8 Dialkylphosphines (223) are no

(222)

(223)

(224)

exception,279and for the acylphosphine (224) it is the CO-P bond that is cleaved the fastest.2soThe spectra of a series of acylphosphines show that the elimination of olefin from the alkyl groups and the formation of hydrocarbon ions become more important as the branching in the alkyl groups increases.280 The cis- and trans-isomers (225) gave identical mass spectra, from which it was Ph,PCH=CHPPh, (225)

a74 a76

a78

(R,N), P C E C P ( N R , Iz (226)

E. A. Ishmaeva, R. A. Cherkasov, V. V. Ovchinnikov, and A. I. Pudovik, J . Gen. Chem. (U.S.S.R.), 1972, 42, 2633. E. M. Gaydou and M. Rajzmann, J. Chim. phys., Physicochim. Biol., 1973, 70, 1207. D. Jannakoudakis, P. G. Mavridis, and N. Missaelidis, Chem. A h . , 1974,80, 103 198. J. Seifert and J. Davidek, 2.Lebensm-Unters. Forsch., 1971, 146, 17. A. N. Pudovik, I. V. Konovalova, G. V. Romanov, and R. G. Fitseva, J. Gen. Chem. (U.S.S.R.), 1973, 43, 38. H. G. De Grad, J. Dubbeldam, and H. Vermeer, Tetrahedron Letters, 1973, 2397. C. Alvarez, A. Cabrera, E. Cortes, and L. J. Gomez, Rev. Latinoamer. Quim., 1973, 4, 197. & R. G. Kostyanovsky, V. G. Plekhanov, Kh. Khakov, L. M. Zagurskaya, G. K. Kadorkina, and Yu. I. Elnatanov, Org. Mass Spectrometry, 1973, 7, 1113.

256

Organophosphorus Chemistry

assumed that there is free rotation about the central C-C bond in the molecular ion.2s1Many of the fragments in the spectra of the bis-phosphinoacetylenes (226) and their chalcogenidesretain the PCCP group. 282 Formation of Hal,P+ is particularly easy for (227), and this ion is responsible for the base

F, PCH, CH, PF, (227)

peak in its spectrum.283Full details of the negative-ion spectra of stabilized ylides have In addition to P- C cleavage, the diphosphonates (228) exhibit C-C bond cleavage when n = 3,4, or 5.286The mass spectra of the thioalkyl phosphonates (229) show that, in contrast to the alkoxy-derivatives, the McLafferty rearrangements are more important than the double hydrogen rearrangements. The metastable defocussing technique was used to show that the ion (230) in the spectra of (229) is derived directly from the

(230)

molecular ions. 286 This fragmentation corresponds to loss of thioaldehyde, which presumably could occur by transfer of an a-hydrogen as shown in (231). The general fragmentation modes for some a-hydroxy-phosphonateshave been determined.287 10 pKa and Thermochemical Studies Some phosphonic acids in alcohols or acetone behave as though they are monobasic when titrated potentiometrically. However, they give two welldefined deflections of the titrimetric curve when DMI? is the solvent.288The pKa values of the first ionization of alkylphosphonic acids (232) increased with 0

II

RP(OH), (232) 881 p8s

OS8

886 486 a87

K. K. Chow and C. A. McAuliffe, J. Organometallic Chem., 1973, 59, 247. W. Kuchen and K. Koch, 2.anorg. Chem., 1972,394,74. K. W. Morse and J. G. Morse, J. Amer. Chem. Soc., 1973, 95, 8469. R. G. Alexander, D. B. Bigley, and J. F. J. Todd, Org. Mass Spectrometry, 1973,7,963. D. J. Whelm and J. C. Johannessen, Austral. J. Chem., 1971, 24, 887. Z. Tashma, J. Katzhendler, and J. Deutsch, Org. Mass Spectrometry, 1973, 7 , 955. K. G. Das and S. K. Saudi, Indian J. Chem., 1973, 11, 552. V. P. Barabanov, V. M. Tsentovskii, A. Ya. Tret’yakova, F. M. Kharrasova, and V. Breenkova,J. Gen. Chem. (U.S.S.R.), 1973,43, 1138.

257

Physical Methods

increasing chain length of the alkyl group but the second ionization constant stopped increasing at hexy1.289The first determinations of the heats of hydrolysis of the very readily hydrolysed phosphate diesters have been reported, and they were in the range 2.7-7.1 kcal m01-1.290 Thermogravimetric analysis has been used to follow the reactions of phosphoroisocyanates (233) with methyl p y r ~ v a t eand , ~ ~the ~ decomposition

I1

Y,PCRZ

I

OH

(233)

(234)

and isomerization of a-hydroxyphosphinates(234).292s 293 Activation energies, specific heats, and enthalpy changes were evaluated for (234).293 11 Surface Properties (Chromatography) The estimation of phosphorus by g.1.c. has been reviewed.294Cyclic phosp h i t e ~ p, h~ o~s~p h o n a t e ~ and ,~~~ phosphates 297 have been analysed by g.1.c. The zinc, gold, and cadmium chelates of dialkyl dithiophosphinates (235 ;

R = Et, Pr, or Bu) are sufficiently volatile for g.1.c. analysis.298A flameionization-flame-emission apparatus for the specific determination of organophosphorus compounds has been described.299 The influence of the adsorbent on the t.1.c. of phosphates and some related P. A. Demchenko and N. A. Yaroshenko, Ukrain. khim. Zhur., 1972,38, 359. J. M. Startevan, J. A. Gerlt, and F. H. Westheimer, J. Amer. Chem. SOC.,1973,95, 8168. A. N. Pudovik, I. V. Konovalova, V. P. Kakurina, and L. A. Burnaeva, J. Gen. Chem. (U.S.S.R.),1973, 43, 556. A. N. Pudovik, I. V. Konovalova, M. Sh. Yagfarov, E. I. Gol'dfarb, and G. V. Romanov, J. Gen. Chem. (U.S.S.R.),1973, 43, 559. G. V. Romanov, M. Sh. Yagfarov, A. I. Konovalov, A. N. Pudovik, I. V. Konovalova, and T. N. Yusupova, J. Gen. Chem. (U.S.S.R.),1973, 43, 2363; A. N. Pudovik, I. V. Konovalova, N. P. Anoshina, and G. V. Romanov, J. Gen. Chem. (U.S.S.R.),1973,43, 2145. M. S. Vigdergauz and Sh. M. Rakhmankulov, Gazov. Khromatogr., 1971, 34; R. F. Addison, Int. Symp. Ident. Meas. Environ. Pollut. (Proc.), 1971, 386. * s 6 R. Vilceanu and P. Schulz, J. Chromatog., 1973, 82, 279. * I e R. Vilceanu, P. Schulz, R. Draghici, and P . Soimu, J. Chromatog., 1973, 82, 285. 2 * 7 A. D. Horton, J. Chromatog. S ci.,1972, 10, 125; A. Brignocchi and G. M. Gasparini, Analyt. Letters, 1973, 6, 523; J. C. Saey, J. Chromatog., 1973, 87, 57; A. Apelblat, J. Inorg. Nuclear Chem., 1973,35,4279. *@ A.I Kleinmann and R. Neeb, Naturwiss., 1973, 60,201. 'Or H. Frostling, J. Phys. (E), 1973, 6, 863.

a8a

258

Organophosphorus Chemistry

phenyl compounds (236) has been examined,300and a number of aqueousorganic solvent mixtures have been recommended as eluants for the t.1.c. of

phosphoric monobasic acids (237).301T.1.c. conditions for determining phosp h ~ r a m i d e sN-acyl-0-methyl ,~~~ derivativesof phosphatidylethanolamines,303 and codeine phosphate 304 have been described. Continuous-flow t.1.c. has been used to measure 32P-labelleddeoxyribonucleosidetriphosphate pools. 305 Ascending paper chromatography has been used to estimate ribonucleoside phosphates,3o6and a new solvent is recommended for the separation of polyphosphates by paper chromatography.307 High-pressure chromatographic separation of phosphates such as glycerophosphates has been achieved using an ammonium formate eluent containing t e t r a b ~ r a t e An . ~ ~amino-acid ~ analyser has been used to estimate L-aminoethylphosphonic The quantitative separation of phosphorus acids and esters by ion-exchange chromatography has been reviewed.310 The separation of nucleoside polyphosphates by anion-exchange chromatography311 and the affinity chromatography of enzymes on immobilized adenosine monophosphate 312 have also been described.

H. Thozet and A. Lamotte, Bull. SOC.chim. France, 1973, 1245. A. Lamotte and A. Francina, J. Chromatog., 1974, 88, 109. a o a R. Reissbrodt, R. Fleischer, and H. J. Fiedler, Arch. Acker-PJanzenbau Bodenk., 1973, 17, 567. I o SR. Sundler and B. Akesson, J. Chromafog., 1973, 80, 233. 1 0 4 W. Schlemmer and E. Kammerl, J. Chromafog., 1973, 82, 143. C. D. Yegian, Analyt. Biochem., 1974,58,231. nag Z . Milewska and H. Penusz, Analyt. Biochem., 1974, 57, 8. T. C. Woodis, J. R. Trimm, and R. D. Duncan, Analyt. Chim. Acta, 1973, 65, 469. * O n D. Lairon, J. Amic, H. Lafont, G. Nalbone, N. Domingo, and J. Hauton, J. Chromatog., I D a *01

so* s10

ala

1974, 88, 183. R. I. Mackie, J. Dairy Sci., 1973, 56, 939. P. Jandera and J. Churacek, J. Chromatog., 1973, 86, 423. V. M. Chernaenko, Priklad. Biokhim. i Mikrobiol., 1973, 9, 918. M. J. Harvey, C. R. Lowe, D. B. Craven, and P. D. G. Dean, European J. Biochem., 1974, 41, 335.

Author Index

Aarons, L. J., 42 Adcock, W., 225 Addison, R. F., 257 Abdel-Maksoud, H. M., 57 Abduvakhabov, A. A., 223 Adamowski, L., 122 Adler, J., 134 Adylov, A. A., 242 Afanas’ev, Yu. N., 48 Afonina, N. N., 250 Aganov, A. V., 120, 234, 243 Agostha, W. C., 165 Aguiar, A. M., 112 Ahrens, J. F., 68 Aida, T., 13, 14 Akamsin, V. D., 92 Akesson, B., 258 Akhmadullina, A. G., 216 Akhmedov, Sh. T., 56, 58 Akintobi, T., 175 Akkerman, V. P., 246 Aksnes, G., 21, 160 Aladzheva, I. M., 24,226 Al’bitskaya, V. M., 91 Albrand, J. P., 230 Alderfer, J. L., 156, 221 Aleksandrova, I. A., 66 Alekseev, A. V., 119 Alexander. R. G.. 256 Aliev, R. Z., 45, 51, 66 Allan, R. D., 86 Allcock, H. R., 182, 202, 252 Allen, C. W., 200 Allen, D. W., 19, 161 Allen, G. W., 103 Almog, J., 219 Althoff, W., 230 Alvarez, C., 255 Ames, D. E., 218 Amic, J., 258 Ammon, H. L., 171, 248 Amos, H., 159 Anan’eva, L. G., 116 Anderson, A. G., 57 Anderson, D. W. W., 231 Anderton, B. H., 147 Andreae, S., 118 Andrewes, A. G., 175 Andrianov. V. G.. 249 Aneja, R., -10, 60 . Ang H. G., 222 Angshina, N. P., 186, 257 Anschutz, W., 70 Antokhina, L. A., 73, 243 Antonoff, R. S.,147 Antonov, I. V., 198, 230

Appel, R., 10, 11, 39, 61, 133, 193 Ape!blat, A., 257 Arai. K.. 97 Arai; Y.; 98 Arbuzov, B. A., 35, 36, 38, 48, 49, 76, 81, 87, 108, 217, 223,242, 254 Archer, B. L., 116 Archie, W. C. jun., 29 Aris, V., 164 Armsen, R., 174 Arnone, A., 132 Arrington, D. E., 182 Arshinova R. P 43, 254 Asabin, Af N., ii)2 Asano, R.. 15 Asano; S.,-80 Ashrafullina, L. Kh., 242 Assmann. G.. 132 Astsatryan, L. E., 58 Atkins, P. W., 55 Audley, B. G., 116 Aumann, G., 153 Austad, T., 14 Auyang, K., 17 Avdonina T. A., 158 Avetisyan: A. A., 58 Avigad, G., 129 Avramova, 0. P., 202 Awad, W. I., 120 Awerbouch, O., 227 Axtell, D. D., 55 Azerbaev, I. N., 87 Azzaro, M., 122 Baalmann, H. H., 193 Baarmann. H.. 45 Babaeva, T. A., 58 Babbina, E. I., 91 Babkova. R. G.. 249 Bach, M: C., 252 Badar, Y.,176 Baddiley, J., 128 Baenziger, N. C., 170, 250 Biir, H.-P., 144, 150 Bahl, C. P., 99, 154, 156 Baigil’dina, S. Yu., 74 Baizer, M. M., 6 Bajgar, J., 136 Balykova, I. A., 79 Bambara, R., 158 Barabanov, V. P., 256 Barker, R., 135 Barnes, F. J., 137 Barnett, B. L., 250 Barnett, J. E. G., 131

259

Barrans, J., 39 Barrett, J. C., 221, 225 Barry, S., 145 Barthelat, M., 242 Bartich, H.-P., 186 Bartlett, P. D., 32, 216 Barton, D. H. R., 86, 219 Bashirova, L. A., 55, 100 Bastien, V., 39 Bates, R. D., 194 Batyeva, E. S., 76, 78, 188 Batyuk, V. A., 103 Baudler, M., 3, 52, 53, 221 Baukov, Yu. I., 8 Baumstark, A. L., 32, 216 Bausher, L. P., 114 Baybutt, P., 247 Bayer, E., 153 Becher, H. J., 5, 53 Beckey, H. D., 130 Beeby, P. J., 177 Ben, M. A. A.. 241 Begum, S., 13 Behrens, N. H., 131 Belkin, Y.V., 35, 81 Bell. A. P.. 171 Bellucci, G., 49 Belov, Yu. P., 79,229, 233, 249.. Bel’skii, V. E., 104, 194 Bender, M. L., 115 Benezra. C.. 233 Benkhuysen, C., 107 Bentham, J. E., 231 Bentrude, W. G., 93, 208, 235.240 Bergeron, C. R., 192 Bergounhou, C., 122 Berastrom. D. E.. 165 BerEe, H.,-172 ’ Berlin, K. D., 112, 123 Bermann. M.. 184. 235 Bernard, ’D., 35, 226 Bernhard, W. A,, 214 Bershas, J. P., 162 Bespalko, G. K., 186 Bessell. E. M.. 130 Bestmbn, H.’J., 166, 168, 171, 174, 176 Bezzubova, N. N., 104 Bickelhaupt, F., 26, 216, 247 Biddlestone, M., 197, 200, 201,202 Biellmann. J. F.. 125 Bigley, D.’B., 256 Bjkhman, B. I., 242 Bilsker, M., 158

260 Binder, H., 91, 121, 185, 223 Binshtok, E. B., 160 Birum, G. H., 65, 75, 113 Biryukov, I. P., 237 Bishop, S. H., 133 Bissell, E. C., 202 Bitko, S. A., 103 Bittner, S., 12 Block, B. P., 201 Bobst, A. M., 156 Bock, H., 191, 247 Bodley, J. W., 223 Boeckman, R. K., 60 Boedeker, J., 242 Boekestein, G., 31, 213, 215, 216, 241 Bohlmann, F., 162,165,176 Bohn, B., 165 Bokanov, A. I., 15, 239, 254 13okii, N. G., 250 13oldesku1, I. E., 24, 246 13olotina, N. A., 242 13one, S., 31 13onjouklian, R., 22, 173 13ordner, J., 15 I3orisenk0, A. A., 4, 49, 94, 95, 222, 232, 235 13orisoya, N. P., 247 130rowitz, I. J., 82 130s. H. J. T.. 68 Bose, A. K., 89 Bose, R., 135 Boswell, K. H., 144, 145 Bottin-Strzalko. T.. 178 Bourgeois, J. hi., 176 Boutagy, J., 178 Bower, R. R., 133 Boyce, C. B. C., 225 Boyer, P. D., 134, 135 Bragin, J., 191, 242 Brandon, R., 6, 208 Brandstetter, F., 153 Branland. G.. 125 Brass, H.*J., i 14, 115 Bratt, J., 77 Braun, R. W., 28, 54, 61, 997 LL I

Brazier, J.-F., 37 Breenkova, V., 256 Brewer, H. B. jun., 132 Brian, C., 252 Bridges, A. J., 9, 68 Brignocchi, A., 257 Brock, C. P., 250 Brodelius, P., 145 Brodsky, L., 162 Brooks, R. J., 103 Broquet, C., 167 Brown, J. D., 243 Brown, J. M., 164, 177 Bruhin, J., 218 Brun, G., 243 Brunelle J. A., 43, 228 Bruniquh, M. F., 196, 249 Brunswick, D. J., 147 Buchanan, G. W., 164 Buchikin, E. P., 122 Buchner, W., 222,227 Buchowiecki, W., 110

Author Index Buck H. M., 17, 18 31, 36,’ 213, 215, 216, ’240, 24 1 Buder, W., 23 Buddrus, J., 160 Biichi. G.. 162 Buerger, H., 241, 244 Bu’lock, J. D., 175 Bullen G. J., 196 200, 202.’203. 230. 25lI 252 Bunnett, J: F., 109, 114 Bunton, C. A., 103 Buono, G., 100, 223 Burachenko, N. A,, 173 Burg, A. B., 44 Burgada, R., 35,36,37,226 Burger, K., 30, 38, 81, 186 Burnaeva, L. A., 257 Burton, D. J., 12, 57, 170, 250 Burzlaff, H., 171 Buschek, J. M., 210 Bushweller, C. H., 43, 228 Buss, B., 198 Butcher, M., 163 Butenko, G. G., 243 Butorina, L. S., 108, 226 Bykhovskaya, E. G., 32,49, 65 Byrne, J. E., 5 Byun, S. M., 131 Cable, H., 221 Cabrera, A., 255 Cadogan, J. I. G., 115 Calas, R., 4 Calhoun, H. P., 72, 203, 205 Callot, H. J., 165 Calvin, M., 14 Cambon, A., 59 Camerman, A., 252 Camerman, N., 252 Cameron, A. F., 202, 250 Cameron, T. S., 236, 250 Campagnari, F., 158 Campbell, M. T., 20 Cantor, C. R., 159 Cardini, C. E., 129 Carey, F. A., 161 Carlson, J. P., 137 Carminatti, H., 131 Carnduff. J.. 57 Carreira,’L.‘A., 15, 54 Carrelhas, A. C., 37 Carrie, R., 169, 234 Carroll. A. P.. 199 Casals,’P.-F., -165 Cashel, M., 149, 153, 223 Castenmiller, W. A. M., 17 Castro, B., 11, 23, 88, 89 Caughlin, C. N., 123 Cavell, R. G., 28, 54, 227, 228.236 Centofanti, L. F., 28, 51 Chachaty, C., 229 Chaiken, I. M., 147 Challis, J. A., 115 Chan, S., 191 m a n , T. H., 68, 70, 74, 120, 207

Chan, Y. F., 35 Chang, L. L., 29, 217 Chapleur, Y., 11, 89 Chappell, J. B., 148 Charbonnel, Y.,39 Chattha, M. S., 112 Chebotareva, E. G., 216 Chekunina, L. I., 2, 239 Chemodanova, L. A., 226 Chen, G. S. H., 61 Cheng, C. Y., 236 Chenier. J. H. B.. 216 Cherkasov, R. -A., 109, 121, 122,253, 254,255 Chernaenko, V. M., 258 Chernov, V. A., 197 Chevnova. A. V.. 243. 245 Chheda, G. B., 142 ’ Chia, L. S. Y.,157, 158 Chibata, J., 126 Chin, K., 175 Chinault, A. C., 147 Chiriac, A 15 Chirkunov;, S. K., 59 Chistokletov, V. N., 12, 95, 192 Chiusoli, G. P., 106 ChlPdek, S., 157 Chow, K. K., 256 Christensen, B. G., 76, 180 Chu, F. Y.,246 Chu, S.-Y., 144 Chuchalin, L. K., 223 Churacek, J., 258 Chwang, A. K., 251 Cichon, J., 241,244 Clare, P., 195 Clark, P. E., 123 Clark, P. W., 1 Clayton, J. P., 185 Cleland, W. W., 152 Clernens, D. F., 187 Clement, B. A., 166 Clerici L., 158 Clifforb, P. J., 108 Clive, D. L.J., 68 Cloyd, J. C., jun., 2, 4, 66, 74,241 Clutter, R., 46 Coburn, W. C. jun., 107, 140. Coddmg, E. G., 43, 246 Coetzee, J. F., 227 Coffin, J. M., 157 Coggon, P., 249 Cohn, K., 42 Collington, E. W., 165 Collins, K. D., 136 Comstock, P., 156 Cook, A. F., 159 Cook. A. G.. 71 Cook; B. R.,‘2 Cook, R. D., 114 Cooke, M. P. jun., 167, 168 Cooke R., 50 Coomh, G. H.,125 Cooper, A., 115 Cooper, D. B., 62, 101, 116 Cooperman, B. S., 147 Corbel, B., 109 Corey, E. J., 162

Author Index Corfield, J. R., 223 Corina, D. L., 131 Corre, E., 35 Cortes, E., 255 Costa, D. J., 28, 54, 229 Cottet, C., 176 Cotton, F. A., 203 Coulter, M. B., 157 Couret, C., 9, 233 Couret, F., 9, 233 Coustures, Y.,249 Cowley, A. H., 15, 28, 29, 43, 54, 61, 227, 228, 248 Cram, D. J., 14 Cramer, F., 144, 153, 157, 159 Crasnier, F., 252 Craven, D. B.,_126. .145. , 258 Cremer, S. E., 19, 47, 236 Cresp, T. M., 173, 174, 177 Cresson, D., 92 Creswell. R. A.. 43. 246 Crofts, P. C., 74, 133 Cross, R. L., 134 Crouch, R. K., 82 Curci, R., 114 Curtis, J. L. S., 1 Dahms, A. S., 135 Dailey, B. P., 194 Daly, J. J., 251 Danchin, A., 152 Dangyan, M. T., 58 Daniewski, W. M., 234 Danion, D., 169, 234 Danion-Bougot, R., 169 Dann, P. E., 196,200, 202, 203, 230, 252 Dannhart, G., 7 Das, K. G., 256 Das, S., 200 Dash, K. C., 25 Da Silva, R. R., 204 Dauben, W. G., 162, 163 Davankov, V. A., 79,249 Davidek, J., 255 Davies, A. G., 208, 212, 214,239,240 Davies, A. P., 10, 60 Davydova, L. Y., 175 Dawson, M. I., 15 De’Ath, N. J., 19, 50, 64 Dean, P. D. G., 126, 145, 258 De Bruin, K. E., 20, 116 de Czekala, A., 159 Degani, C., 135 de Graaf, H. G., 216,255 De Haan, J. W., 17 Deich, A. Ya., 237 de Jong, L. P. A., 137 Deleris, G., 4 Del’tsova, D. P., 166 Dembech, P., 234 Demchenko, P. A., 257 Demir T.,236 D q f i h i e r Aldao, E. M., ILI

Demuth, R., 53, 241, 244, 252

261 Deiiney, D. B., 29, 30, 217 Dennis, L. W., 242 Dennis, R. W., 210, 214 Denyer, C. V., 68 Denzel, J., 166 De Pamphilis, M. L., 152 Derkach, G. I., 183, 186 de Rooy, J. F. M., 145 Desai, V. B., 196, 230 Deschamps, B., 178 de Silva, S. O., 173 Deutsch, J., 256 Devlin, C. J., 16, 79 Dewar, M. J. S., 15, 29, 43, 54, 210, 225, 248 Diamond, J., 17 Dianova, E. N., 217 Diebert, C. E., 114 Dieck, R. L., 195 Diemert, K., 234 Dietz, E. A., 1, 44 Dimroth, K., 24, 25, 248 Dmitrieva. G. V.. 66 Dmitrieva; N. V.; 47, 111 Dobbers, J., 221 Dobbie, R. C., 214, 243 Doel, M. T., 155 Docradina. A. V.. 111 Doc K., 202 ’ Dolgushina, I. U., 61 Dombrovskii, A. V., 16, 173, 245 Domingo, N., 258 Donskaya, Y.A., 73, 122, 243

D&&ay, B., 11 Dormoy, J. R., 12, 23, 89 Dorokhova. V. V.. 236, 243, 246,‘247 . Dostal, K., 201 Dougill, M. W., 203 Drach, B. S., 61 Drarzhici. R.. 257 Drago, R. S., 225 Dreissig, W., 249, 250 Dubbeldam, J., 255 Duff, E., 85 Dumas, L. B., 151 Duncan, R. D., 258 Dunn, B. M.,147 Dunogues, J., 4 Dupre, M., 69 Durig, J. R., 15, 54, 242 Durrieu, J., 235 Dyadusha, G. G., 189 D’yakov, V. M., 80,244 D’yakonov, D. N., 91 Dyaltona, N. M., 242 Dyer, R. L., 108 Dzhanddzhadanyan, A. N., 58 I

Eastlick, D. T., 115 Eaton M. A. W., 156 Ebitinb, F. F.,217 Ebert, .H.-D., 64 Eberlein. J.. 25 Eckes,-H., 70 Ekkstein F 142 150 159 fidel’m&, ’?. G.,’191,’247 Edwards, J. O., 114

Efremova, M. V., 104 Egan, W., 228 Egorov, Yu. P., 24, 123, 183, 186, 195, 221, 222, 237, 239, 242, 244, 246, 247, 249, 253, 254 Eichhorn, B., 35, 44 Eidem, A., 175 Einhellig, K., 38 Eizember, R. F., 165 Elbein, A. D., 131 El-DWk, M., 120 Elder. R. C.. 51. 92. 112. 234 Elegant, L.: 122 Eliseenkova, R. M., 92 Elkaim. J.-C.. 122.225.226 El-Khoshnieh, Y: 0..~ :85. 215 Ellermann, J., 4, 87 Elliott, L. E., 53 Elnatanov. Yu.I.. 255 El-Sawi.-E.. 120 ’ Elzaro, R. A., 246 Emoto, T., 206 Emsley, J., 47, 228, 241 Endo. K.. 17 Endo: T..? 154 Englard, ’S., 129 Epaud, R. M., 137 Erickson B. W., 162 Ermo1ae;a. M. V.. 117 Bryan, M.’A., 182 Escudie, J., 9,233 Estacio, P., 53 Eto, M.,105 Evans, M. M., 12 Evstaf’ev, G. I., 120, 121, 234 Ezra, F. S., 214 ,

I

,

,

Faler, G. R., 219 Falius, H. H., 185 Fan, F. R., 19,47 Fasold, H., 147 Faucher, J.-P., 195,196,249 Fazliev. D. F.. 243 Featheknan S. I., 223 Fedin, E. I.,’ 172 Fedorova, G. K., 116 Fehn, J., 30, 81, 186 Feistel, G. R., 195 Feldt, M.K., 195 Fell. B.. 45 Fenske D., 53,250 Ferard,’ J., 165 Ferguson J. J., jun., 147 FernandGz-Phi, R., 102 Feshchenko, N. G., 24, 45 Fey, G. T. K., 243 Fjedler, H. J., 258 Fields E. S 60 Fild M 4iy230 Filiipo; E.’A 201 Finch, d. 175” Finkelhoi R. S., 119, 180 Finkenbine. J. R.. 68 Firestone, R. A., -133 Fischer, E. H., 50 Fischer R., 91, 185 Fisher, ’G.S., 138, 208

Author Index

262 Fishman, A. I., 43, 242 Fitseva, R. G., 255 Fitt, J. J., 175 Flatau. G. N.. 59 Fleischer, R., 258 Flick, W., 182 Flintoff, W. F., 157 Florian, L. R., 51,92, 112, 234 Fluck, E., 58, 121, 230, 186, 221, 223 Fokin, A. V., 54, 56, 221, 223 Folayan, J. O., 156 Fomichev, A. A., 14, 229 Fomin, A. A., 199, 230 Fontal, B., 54 Font Freide, J. J. H. M., 18, 213, 240 Formoso, C., 159 Foroughi, K., 41, 91, 233 Foss, V. L., 4, 49, 94, 95, 222 Foster, A. B., 130 Foucaud, A., 12, 35, 88 Foucaud, B. Y., 125 Francina, A., 258 Franko-Filipasic, B. R., 20 1 Franze, K. D., 2 Fraser, T. H., 157 Fraty, A. E., 6 Frazier, J., 156 Freeman, B. H., 13 Freist, W., 144 Frejd, T., 107 Freze, R., 100 Frolov, Yu. I., 243 Frostling, H., 257 Friderici, K., 156 Fridland, S. V., 47, 57, 58, 59,111 Fuchila, J., 145 Fuchs, P. L., 23, 68, 162, 166,224 Fuertes, M., 143 Fukuhara, G., 217 Fukui, T., 142 Fukumoto, K., 217 Fujita, Y., 238 Fujiwara, Y., 15 Furukawa, N., 13, 14 Furun, G. G., 55 Furuta, 0. K., 76 Fuzhenkova, A. V., 36,76, 81 Gabriel, T. F., 159 Gachegov, Yu. N., 55 Gaede, K., 137 Gagnaire, D., 230 Gaidamaka, S. N., 55, 222 Gainullina, R. G., 108 Gal, J. Y.,104, 106, 215 Galishev, V. A., 12, 192 Gal’tsova, E. A., 223, 250 Galyautdinova, A. A., 48 Gamaleya, V. F., 76 Gambaryan, N. P., 166 Gammel, D., 5 Ganem, B., 60

Garatt, P. J., 177 Garcia-Blanco, S.. 252 Gareev. R. D..~.120, 226. 234 Gargus, J. J., 134 Garrigues, B., 242 Garron, P. E., 1 Garst. M. E.. 22 Gartman, G..A., 79 Garwood, D. C., 14 Gasparini, G. M., 257 Gasparoni, F., 106 Gay, R. S., 54 Gaydou, E. M., 100, 123, 225 Gazetdinova, N. G., 238 Gazizov, M. B., 48, 95 Gazizov, T. Kh., 80 Gennaro. G. P.. 54 Genoud,‘L., 104 Gentile, B., 176 Geoffroy, M., 209, 238 Gergely, J., 241 Gerlt. J. A.. 101. 135. 257 Germain, G., 251 ’ Gester, R., 104 Gestrelius, S., 145 Ghalambor, M. A., 131 Gick, W., 187 Gieren, A., 30, 186 Giesen, K.-P., 185 Giles, R. G. F., 174 Gilham, P. T., 157 GiAjzAJ. W., 28, 43, 54, 61, LL I

Gillen, K. T., 236 Gilles, L., 106, 215 Gilyarov, V. A., 38, 233 Giniyatullin, R. S., 242 Ginns, I. S., 215 Girardi, F., 158 Girijavallabhan, M., 86 Gitel’, P. O., 146 Glaser. S. L.. 97. 123 Glassel, W., 192‘ Glemser, O., 198 Glidewell, C., 53 Gloede, J., 66 Glonek, T., 132, 133, 223 Glynn, I. M., 148 Godici, P. E., 236 Goerdeler, J., 219 Gohil, R. N., 144 Golborn, P., 113 Gol’dfarb, E. I., 46, 49, 223.237.257 Golding, B. T., 164 Goldwhite, H., 191 Golik, G. A., 183, 186, 189 Golling, R., 144 Gololobov, Y. G., 101 Gomez, L. J., 255 Goodbrand, H. B., 21, 166 Goodfellow; R. J., 137 Goodfriend, P. L., 206 Goodman, D. W., 15, 29, 43. 54. 248 Goody, R. S., 150 Gorbatenko, Zh. K., 45 Gordeev, A. D., 55, 189, 237 -

7

-

7

-

Gorenstein, D., 21 Gorin, P. A. J., 129, 223 Gorin, Ya. A., 57 Gorokho?, V. I., 202 Goswami, R., 168 Goto, K., 227 Goto, M., 139 Gottfried, K. H., 248 Goubeau, J., 244 Cough, G. R., 50 Graham, J. C., 193 Gratecos. D.. 150 Gratzer, ‘W. B., 158 Gray, G. A., 19, 47, 137, 223, 236 Grayson, S. J., 19 Grechkin, E. F., 59, 236, 243. 246. 247 Greene, G: L., 142 Greenwell, P., 126 Gregonis, D. E., 137 Grekov, A. P., 90 Greve, W., 78, 130, 234 Grieco. P. A.. 119. 180 Griffin; C. E.; 234’ Griffiths, N. D., 218 Griller, D., 52, 208, 211, 212. 239. 240 Grim.-S. 0.. 65 Grimmer, A.-R., 61 Grinberg, S., 12 Grinblat, M. P., 61 Grishina. L. N.. 253 Grobe, J:, 52, 241, 244 Gross, B., 11, 89 Gross, D., 175 Grossman, G., 221 Gruber, W. H., 4, 87 Gruk, M. P., 36, 81 Grynkiewicz, G., 83 Guest, M. F., 42, 247 Guilford, H., 147 Gulyaeva, N. A., 252 Gupta, B. D., 225 Gupta, R. C., 157 Gurevich, P. A., 74 Gur’yanova, E. N., 15, 246,254 Gusenkova, N. M., 242 Gusev, A. I., 250 Guseva, F., 108 Gustafson, A. E., 164 Guthrow, C. E., 147 Haag, J., 219 Haake, P., 103, 114, 115 Haar, W., 137 Habib, Z., 13 Haegele, G., 234 Haemers, M., 232 Hagen, A. R., 251 Hagenbach, A., 15 Hagens, W., 68 Hair. N. J.. 202. 250 Hajra, A. K., 136 Halasa, A. F., 201 Hall, C. D., 108, 171 Hall, C. R., 67, 187 Hall, J. E., 201 Hall, M. B., 42 Hall, W. R., 42, 254

263

Author Index 1Kallab, M., 3, 53

1Hamasaki, T., 175 1Hameka, H. F., 42, 254 1Hamel, E., 153 1Hamelin, J., 169 1Hamilton. W. C.. 39. 83. 252 1Kampton, A., 142, 143 1Hansen, K. C., 14 1Hansen. K. J.. 218 IHansen; R. S.; 231 1Hanson, M., 223 1Hanzawa, Y., 59 1Hapke, B., 151 1Yarger, M. J. P., 114 1Hargis, J. H., 240 1Tarland, P. W., 44 IFIarness, I., 19 1Yaroz, R. K., 157 1Harper, P. J., 142 1Harpp, D. N., 13, 86, 219 1Harris. M. M., 111 1Harris; R., 144 1Harrison, J. M., 101, 105, 116 1!Iart, D. J., 162 1Hartman, F. C., 135, 136 1Hartman, K. A., 159 1Hartmann, A., 120, 206 1Hartwell, G. E., 1 13arvev. C. L.. 159 13arve$; M. J., 126, 145, 258 I?[asan, M., 196, 249 1lassairi, M., 88 1laszeldine. R. N.. 6.208 ‘ 1lata, T., 98, 124 . 1lattori, M., 142 1lausard, M., 5 5 , 249 1lauser, A., 232 1-Tauton,J., 258 Ilayashi, T., 197 Ilayes, F. N., 157 Ilays, H. R., 62 Ilazvanova, G. F., 226 Ileatley, P., 161 Ilecht, S. M., 147, 148 I3eckmann, G., 221,230 I3eesing, A., 88 Iieider, W., 198 I3eik P., 124 I-Iell&nkel, D., 32 Ilellyer, J. M., 103 IJenderson. T. 0. ,.132.133, 223‘ Hendrick, P. K., 4, 66 Hennig, H. J., 7 Henzel. R. P.. 165 Herrmann, E., 183 Hettler, H., 144 Heyer, G., 52 Higashi F., 91 Hilderbiand, R. L., 133 Hill, D. L., 139 Hjllier, I. H., 42, 247 Hintz, P. J., 210 Hjpwell, M. C., 145 Hirano, Y.,71, 207 Hjratsuka, T., 50 Hirth, C. G., 125 Hobbs, J., 142 _

I

,

Hochleitner, R., 64 Hoefler, F., 244 Horster, H.-G., 219 Hoffman. P.. 33. 54 Hogg, R.’ W:, 134 Holland, C. L., 14 Hollis, D. P., 137 Holman, M., 159 Holmes, A. B., 177 Holmes, R. R., 243 Holtz, H. D., 13, 66, 216 Holy, A., 142 Honda, A., 154 Honda, M., 60 Hong, C. I., 142 Honig, M. L., 82, 99 Horn, F., 58, 186 Homer, L., 5 Horton, A. D., 257 Horvath, C., 159 Houalla, D., 37, 40, 227 Howard, F. B., 156 Howard, J. A., 27,216,252 Howell, J. M., 54 Howells, D., 69, 70 Howells, M. A., 170, 250 Howells, R. D., 170, 250 Howgate, P., 142 Howlett, K. D., 236, 250 Hruska, F. E., 221, 235 Hubbard, R., 185 Huche, M., 92 Hudson, H. R., 75 Hulla, F. W., 147 Humphris, K. J., 216 Hutchinson, D. W., 156 Hutley, B. G., 19, 161 Hwang, H.-O., 19,47 Hwang, J.-T., 161 Hyde, R. G., 42,254 Ibaiiez, F., 121 Ibers, J. M., 250 Ignat’ev, V. M., 74, 111 Ignatova, N. P., 249 Iguchi, I., 91 Iida, Y.,241 Ike, T., 175 Ikeda. K.. 154 Ikehah-M., 99, 142, 146, 152, 154, 155, 156 Ikemoto, I., 248 Ikeno, S., 202 Illger, W., 70 Il’yasov, A. V., 237 Imsieke, G., 88 Inaba, J., 142 Inada, T., 179 Inamoto, N., 70, 71, 118, 206, 207, 223 Inanaga, J., 175 Inch, T. D., 62, 101, 105, 116 Indzhikyan, M. G., 21 Ingold, K. U., 208, 216, 240 Ingrosso, G., 49 Ioffe, S. T., 245 Ionin, B. I., 71, 74, 111, 226. 229.233 Ipaktschi, J., 162

Ireland, R. E., 15 Irving, J. T., 124 Isaacs, N. S., 57 Ishii, Y., 18, 190 Ishikawa, F., 156 Ishmaeva, E. A., 242, 254, 255 Ismagilova, N. M., 80 lsmailov. V. M.. 56. 58 Issleib, K.,2, 3,’4, 6, 7, 8, Itakura, 88,222K., 99, 154, 155, 156 Ito, Y., 201 Itoh, K., 18, 190 Ivanov, Y. A., 122 Ivanova, G. S., 142 Ivanova, R. G., 48 Ivanovshaya, K. M., 223 Ivanovskii, M. D., 202 Iwacha, D. J., 146 Iwata, T., 107, 139, 140 Izawa, Y.,63, 71, 204, 207 Jaenicke, L., 175 Jackson, J. A., 242 Jacobus, J., 228 Jaffe, H., 101 Jakobsen, H. J., 223, 231 Jakobson, G. G., 55 Jandera, P., 258 Jannakoudakis, D., 255 Jansen, E. H. J. M., 31, 213, 215 Janson, C. A., 152 Janssen, E., 194, 195 Jardetzky, O., 137 Jarman, M., 130 Jarvis, B. B., 12 Jastorff, B., 144, 145 Jay E., 155 158 Jeahlor R.’W., 130, 131 Jeck, R:, 124 Jenness, R., 131 Jennings, W. B., 210 Jenny, W., 218 Jensen, L. H., 128 Jensen, W., 251 Jewett, S. L., 126 Johannessen J. C., 256 Johansen, J.’E., 175 Johnson D. M 20, 116 Johnson: L. F.,”132 Johnson Q., 251 Johnson’ W. S., 165 Jolicoeu;, C., 246 Jonas, J., 236 Jones, C. E., 43 Jones, C. R., 159 Jones, G. H., 144 Jones, M. R., 14 Jongsma, C., 216 Joo, C. N 138 Jordan, AYD., 236 Jordan F., 221 Jordan: R. B., 236 Jourdan G., 243 Jugelt, W., 118 Jung, M. J., 125 Jungermann, E., 46 Junkes, P.,64, 221

Author Index

264

Khalil, F. Y.,21, 160 Khalitov, F. G., 73, 122,

Kossel, H., 155 Koster, H., 153 Kohn, B. D., 142 Kohn, P., 142 Koide, T., 142 Koizumi, T., 41, 98, 106,

Khan. M. K.. 156 Khan; S. A., ‘13 Kharrasova, F. M., 256 Khasanov, M. K., 8 Khaskin, B. A., 110 Khimchenko, T. A., 123 Khomenko, D. P., 189,249 Khranenko, S. P., 223 Khwaja, T. A., 144, 159 Kielanowska, M., 156 Kienhuis, H., 115 Kieselack, P., 24 Kim, Y. J., 113 Kimpenhaus, W., 160 Kimura, H., 145 King, J. P., 201 King, R. B., 4, 6, 66, 74,

Kolata, G. B., 145 Kolbina, V. E., 247 Kolli, I. D., 246 Kolmykova, N. N., 202 Kolodyazhnyi, 0. I., 101 Kolomiets, A. F., 56 Kolyubakina, D. G., 216 Komlev, I. V., 222 Konami, Y., 131 Kondo, H., 102, 126 Konieczny, M., 122 Konlev, I. V., 81 Konno, M., 250 Kono, D. H., 57 Kononenko, I. M., 116 Konovalova, A. I., 257 Konovalova, I. V., 255,

Kinnick, M. D., 76, 179 Kinoshita, M., 111 Kirchner, C. R., 144 Kireev, V. V., 182, 199,

Konstantinovskay, M., 66 Konyaeva, I. P., 81 Konysbaev, Zh. K., 87 Kopp, R. W., 19 Koppel, G. A., 76, 179 Koppes, W. E., 57 Kordosky, G., 2 Kormachev, V. V., 58 Korman, E. F., 133, 134,

Juodka, B. A., 143

Khairullin, V. K., 45, 51,

Kaack, H., 1 Kabachnik, M. I., 24, 38,

Khalaturnik, M. V., 16,

66, 72, 108, 172, 226, 233, 245 Kabankin, A. S., 54, 221, 223 Kadokura, T., 201 Kadorkina, G. K., 255 Kaiser, E. M., 106 Kajiura, M., 201 Kajiwara, M., 189 Kakhar, V. P., 247 Kakurina, V. P., 257 Kalabina, A. V., 243, 247 Kalenskaya, A. I., 197 Kalinin, A. E., 250 Kalvoda, L., 138 Kalyagin, G. A., 101 Kamaguchi, K., 139 Kamai, G. Kh., 48 Kametani, T., 217 Kammerl, E., 258 Kan, L. S., 221, 225, 227 Kanamoto, N., 102 Kanazawa, T., 135 Kando, K., 180 Kaneko, T., 165 Kao, J. T. F., 192 Kaplan, N. O., 125 Kapoor, P. N., 4, 74, 241 Kappler, F., 142 Karas, G., 108 Kariya, T., 248 Karlsson, K. A., 133 Karsch. H. H., 169 Kartoon, I., 12 Kasheva, T. N., 182, 189 Kashman, Y.,6, 227 Kaska. W. C.,. 169,. 172,205 Kaspruk, B. I., 122 Katagiri, K., 139 Katagiri, N., 99, 154, 155, 156 Kates, M., 138 Kato, S., 18 Kato, T., 18 Katolichenko, V. I., 254 Katz, T. J., 32, 205 Katzhendler, J., 256 Katzu, T., 238 Kawamoto, I., 17 Kawamura, H., 201 Kawamura. Y..154 Kawasaki, Y., 244 Kay, C. M., 152 Kearns, D. R., 159 Keat, R., 182, 236 Keijzer, J. H., 137 Kennedy, E. R., 511, 92, 112,234 Kennedy, J. D., 229 Kenney, R. L., 138, 208 Kenyon, G. L.,63 Keravec, M., 165 Kerr, C. M. L.,238 Kessel, A. Y.,122 Khachatryan, R. A.,I 2 1 Khafizov, Kh., 255 ‘

66

245

237, 243

24 1

201, 202, 230

Kireeva, A. Yu., 242 Kirilov, M., 119, 220 Kirkpatrick, D., 57 Kirkpatrick, D. S., 133 Kirkwood, S., 131 Kirpichnikov, P. A., 216, 237, 239

Kirsanov, A. V., 28, 88,

116 186, 189, 191 Kisilgnko, A. A., 242, 244, 247 Kisselev, L. L., 158 Kitos, P. A., 159 Kitahara. T., 80 Kjmen, H., 175 Klaebe A. 37 Kleba&ki,’A. L., 61, ,98 Kleiman, Yu. L., 229 Klein, H.-F., 169 Klelner, H.-J., 44 Kleinmann. A.. 257 kleinstuck,’ R.,’ 10 Klingebiel, U., 198 Klingl, H., 41, 91 Kluger, R., 116 Klusmann, P., 187 Knaggs, J. A., 10, 60 Kneidd, F., 24 Knight, D. W., 176 Knunyants, I. L., 32 49, 65, 117, 166 Kobayashj, E., 201 Kobavashi. T.. 173 Kobaiashi; Y.;59, 60 Koch. K., 256 Kocheshkov, K. A., 254 Kochetkov, N. K., 128, 129 Kochmann, W., 16 Koehler H., 223 Koenig,’M., 39, 40 Kornig, D., 165, 176

115

257

149

Komuta, P. P., 195, 197, 237, 244

Korol’ko, V. V., 198 Korshak. V. V.. 182. 199. 202,230

Korte, W. D., 169 Kosinskaya, I. M., 186 Kosmus. W.. 42 Kosolapoff, G. M., 62, 133 Kossmehl, G., 165 Kostyanovskii, R. G., 14, 229.255

Kostynk, A. S., 8 Kotte, P., 223 KZyLkes-Pujo, A. M., 106, L1-l

Kovtun, V. Yu., 233 Kozarich, J. W., 147, 148 Kozhushko, B. N., 88 Kozikowski, A. P., 162, 163

Kozlov, E. S., 55, 182, 189, 237

Kozlov, N. S., 79 Kozlova, R. I., 243 Krabbes, G., 221 Kraemer, R., 235 Kramer, J. K. G., 138 Kramer, L., 39, 83, 252 Krasilov, A. M., 58 Kratzer, O., 174 Kraus, J.-L., 179 Kraut, A., 135 Krawiecka, B., 96 Kreiser, W., 179 Kreiss, W., 95

Author Index Kremer, P. W., 19, 47 Kren, R. M., 51 Krishnamurthy, S. S., 196, 200, 249

Kroner, J., 247 Kropacheva, A. A., 197 Kropp, P. J., 204 Krueger, C., 250 Krueger, W. E., 79 Kruglov, S. V., 74, 111 Krupnov, V. K., 48 Krushi, A. W., 132 Krusic, P. J., 210 Kryuchkov, A. A., 254 Kubardin, A. M., 80 Kuchar, S., 129 Kuchen, W., 234.256 Kudinova, V. V., 4,94,222 Kuehl, L., 137 Kukhar’, V. P., 182, 186, 189, 191

Kukhtenko, I. I., 226 Kukhtin, V. A., 58 Kula, M.-R., 142, 144 Kumadaki, I., 59, 60 Kuramshin, I., Ya., 43, 123, 242, 243

Kuroda. H.. 248 Kurras,‘E., -169 Kurz, J., 223 Kusmierek, J. T., 156 Kusov Y. Y., 129 Kutyriv, G. A., 109, 254 Kwan. T.. 238 Kyuntsel’; 1. A., 189 Kuz’minzkii, B. N., 239 Labarre, J.-F., 195, 196, 249, 252

Labarre, M. C., 55, 249 Labaw, C. S., 22 Lachkova. V.. 120 Lafont, H;,258 Lairon, D., 258 Lal, B., 89 Lamotte, A., 258 Lamprecht, W., 150 Landau, M. A,, 54, 221, 223

Landis, M. E.. 32, 216 Landsberger, F. R., 236 Lane, M. D., 128 Langer, E., 5, 53 Larkin J., 57 Larkin: R. H., 243 Larsen, S . H., 134 Larsson, P. O., 125 Laskorin, B. N., 122 Laster, W. R. jun., 107, 139, 140

Laurenco, C., 36, 37 Laurent’ev, A. N., 5 Lawesson, LO.,107 Leary, R. D., 228 Le Come, M., 165 Lee. C.-H. 221 Lee; M. Y.,110 Lee, P. L., 42 Lefebvre, G., 178 Leffler, J. E., 101

265 Le Geyt, M. R., 72, 250 Legin, G. Ya., 45 Le Griis, P. G., 108 Leguern, D., 12 Lehmann, H., 175 Lehnert, W., 113 Leibovici, C., 42, 250 Leissring, E., 8 Leloir, L. F., 131 Leloir, L. L., 129 Lemmon, D. H., 242 Lemmen, P., 97 Lennarz, W. J., 130 Lequan, R.-M., 72, 232 Leroux, Y., 109 Lesigne, B., 106, 215 Letsinger, R. L., 142, 151 Lewis, D. J., 136 Lewis, E. S., 82 Lewis, G. J., 62, 101, 105, 116

Lewis, R. C., 21, 75 Levchuk, Yu. N., 183, 186 Levin, Ya. A., 46, 111, 237 Levy, H. M., 135 Li, N. C., 227 Liaaen-Jensen, S., 175 Liedhegener, A., 70 Lin, F., 33 Lin, H. L., 122 Lin, T.-P., 198 Lin. W. H.. 57 Lindberg, M.,125 Linder, E., 172 Lindner, C., 219 Lindner, E., 64 Lindner, W., 32 Lingens, F., 133 Lion, Y.,241 Liorber, B. G., 226, 245 Lipatova, I. P., 122, 244,

245

Llinas, J. R., 231 Lloyd, D., 13 Lischewski, M., 4, 88, 222 Liu, N. I., 236 Liu, Y., 180 Lobachev, V. M., 242 Lobanov, D. I., 72 Lockley, W. J. S., 176 Loens, J., 250 Loginova, E. I., 231 Lohrmann, R., 145 Lomonosov, A. V., 2011 Lorberth. J.. 191 Losch, R:, 219 Lowe, C. R., 145,258 Lowe, G., 136 Luckenbach, R., 4, 19, 20, 63

Lugovkin, B. P., 79 Lukin, A. M., 242 Lutsenko, I. F., 4, 8, 49, 94,95, 222

Ly M 11 88 Lyki&i, 6. P., 104 McAuliffe, C. A., 256 McBride, J. J., 46 McCarl, R. L., 128 McCarry, B. E., 165

McConnell, B., 227 McCubbin, W. C., 152 McCutchan, T. F., 157 McFarlane, W., 72, 229, 23 1

Mclntosh, J. M., 21, 166 Mackie, R. I., 258 McLick, J., 133, 134, 149 MacNamee, R. W., 242 Macomber, R. S., 51, 92, .

112, 234

McPhail, A. T., 249 Maekawa, E., 174 Maelicke, A., 159 Markl, G., 7, 24, 163, 248 Magnus, P. D., 219 Maguire, M. H., 50 Mahan, J. E., 13, 66, 216 Mahran, M. R., 85, 215 Maier L., 46, 62, 121, 223, 234, 251

Maijs, L., 248 Maikuma. T., 201 Mais, A.,-46 . Majoral, J. P., 122 Makarov, A. B., 249 Makarov. N. A.. 49 Makhamatkhanov, M. M., 72

Makhon’kov, D. I., 7 Makovostskii, Y. P., 24 Maksyutin, Yu. K., 236 Maksyutina, L. I., 116 Malchow, D., 145 Malkievicz, A., 156 Malkov, Yu. K.,58, 59 Mallinson, P. R., 252 Mallory, F. B., 229 Malone, G. R., 75, 173 Maloney, J. R., 79 Malotki, P., 6 Mannafov, T. G., 243 Manor, P. C., 251 Marata, Y., 231 Marcantonatis, M., 104 Marecek, J., 35 Maria, P. C., 122 Marino, J. P., 165 Marioni, F., 49 Markezich, R. L., 165 Markham, R. T., 1, 44 Markovskij, L. N., 28 Markowska, A., 110 Marmor, R. S., 119, 179 Marner, F.-J., 175 Marquarding, D., 33, 35 Marriott, R. C.,6 Marshall, J. A., 204 Marsi. K. L.. 4. 66 Marsili, A,, 49 ’ Marszak, M. B., 69 Martell, A. E., 102, 126 Martial. J.. 126 Martin ’D: R. 1, 44 Martinkt, J. P., 104 Martinez, E. L., jun., 157 Martinson, H. G., 159 Martynyuk, A. P., 191, 239, 247

Masamuni, Y.,102 Mashlyakovskii, L. N., 111

Author Index

266 Maslennikov, I. G., 5 Masler, W. F., 2 Mason, G. W., 71 Masse, G. M., 21 Mastalerz, P., 113 Mastryukova, T. A., 24, 108, 172, 226, 245 Mathews, R. J., 44, 163 Mathey, F., 24 Mathis, F., 39 Mathis, R., 242 Mathur, M. A., 51 Matienzo. L. J.. 65 Matroso;, E. I., 24, 172, 226, 245 Matsumoto, S., 107, 139 140 Matsui, M., 80 Mattes, R., 250 Matuo, Y., 126 Mauck, M., 183 Maurer, W., 137 Mavridis, P. G., 255 Mazalov, L. N., 250 Mazzola, E., 191 Meadows, D. H., 137 Meakin, P., 210 Medved, T. Y.,66 Medvedev. V. I.. 122 Megera, I.‘ V., 173 Mejzlik, J., 201 Mellor, M. T. J., 161 Mel’nikov. N. N.. 110 Mendenhall, G. D., 85 Mennenga, H., 169 Merkulov, A. V., 58 Merz, A., 163 Meyer, R. B., jun., 144 Meyers, A. I., 75, 165, 173 Mian, A. M., 144 Michaelewsky, J. E., 159 Michalski, J., 96 Michniewicz, J. J., 99, 154, 156 Middleton, S., 163 Middleton, T. B., 47, 241 Mihaly, E., 176 Mikolajczyk, M., 75, 114 179, 251 Mjles, H. T., 142, 156 Milewska. Z.. 258 Milicev, S., 73 Milker, R., 39 Miller, J. A., 19, 50, 57, 64, 65 Miller, J. P., 144, 145 Miller, P. S., 142, 221 Miller. R. S.. 128 Miller; S. I.,’22, 172 Millington, D., 195, 196 Minas’yan, R. M., 182 Mironova, 2.N., 223 Mishchenko, V. V., 175 Mishra, S. P., 55, 122, 209, 215, 238 Mislow, K., 14 Missaelidis, N., 255 Misumi, S., 173 Mitchell, D. K., 169 Mitchell, P., 135 Mitchell, R. H., 219

M itschke, K. H., 227 M iyagi, T., 201 M iyaoka, T., 154 M lizuno, Y., 154 M izuta, M., 18 M lotkowska, B., 105 M odro, T. A., 120 M ‘oedritzer, K., 51, 226 M Ioeller, T., 195 M offatt, J. G., 144 M ohr, K., 8

M,ol’nikov, N. N., 249 M lolyavko, L. I., 76 M [omsen, W., 134 M ontemayor, R. G., 44 M jootz, D., 27 M orel, G., 12 M [orelli, I., 49 M [organ, A. R., 157 M orioka, S., 99, 154, 155 M oritani, I., 15 M orkovin, N. V., 229 M orr, M., 142, 144 M orris, D. G., 202, 250 M orrison, J. D., 2 M orse, J. G., 43, 45, 206, 256 M orse, K. W., 45, 206,256 M orton, J. R., 55 M osbach, K., 125, 145 M osbo, J. A., 93, 123, 227 M oskva, V. V., 55, 56, 58, 100, 226 M owat, I. W., 19 M uetterties, E. L., 54 M ukhametov, F. S., 245 M ukhina, L. E., 197 M ukmenev, E. T., 49, 199 M ukmeneva, N. A., 216, 239 M uller, W., 159 M uneyama, K., 144, 145 M unpall. W. S.. 142 Munoz, A., 39,‘40 Murad, F., 145 Murakami, Y., 102, 126, 225, 226 Murata, Y., 171 Muratova, A. A., 242, 243 Murayama, A., 144 Murdoch, L., 50 Murthy, D. V. K., 144 Muscio, F., 137 Muscio, 0. J., 137 Myers, T. C., 132, 133 Mynott, R. J., 221, 235

Naae, D. G., 12 Naan, M. P., 171 Nachbaur, E., 42 Nagura, T., 145 Nagyvary, J., 143, 144 Nakagawa, I., 98, 124 Nakamura, K., 202 Nakanishi, A., 100 Nakano. A.. 175 Nakayama,’S., 70, 71 118, 207, 223 Nalbone, G., 258 Narang, S. A., 99, 154, 155, 156 9

Narayanan, P., 30, 186 arwid, T. A., 165 Nasonovskii, I. S., 235,254 Naumov, V. A., 194, 252, 253 Navech, J., 122, 235 Nazarov, V. S., 80 Nechaev, U. D., 229 N e b , R., 257 Neef, G., 179 Neilson, T., 155 Neimysheva, A. A., 117 Nelsen, S . F., 210 Nesmeyanov, N. A., 160 Nesterenko, V. D., 188 Nesterov, L. V., 122 Nesterova, N. P., 66 Neta, P., 108, 214 Neufeld, A. N., 135 Niecke, E., 182 Nieh, E. C., 82 Nifant’ev, E. E., 81, 222, 226,232, 235,254 Nikolaev, A. V., 250 Nikonova, L. Z., 49, 108, 254 Nishiwaki, T., 217 Noguti, Y.,248 Nolen, R. L., 165 Nonhebel, D. C., 57 Nordeen, C. W., 133 Norman, E. J., 143 Norris, R. K., 219 Norton, I. L., 136 Novosel’skaya, A. D., 87 Novruzov, S. A., 56, 58 Nowak, B. J., 158 Nowoswiat, E. F., 155 Nozaki, H., 118, 180 Nunn, M. J., 19, 50, 64, 65 Nuretdinov, I. A., 104, 194, 231, 236 Nuretdinova. 0. N.. 49. 108,254 Nurtdinov. S. Kh., 80 Nussbaum, A. L., 155, 159 Nwe, K. T., 70, 120, 207 ~I

Oae, S., 13, 14, 100 Oberhammer, H., 53, 252, 253 O’Brien, W. E., 128 O’Carra, P., 145 Odom, J. D., 6, 15 Oehme, G., 169 Oehme, H., 8, 232 Ogawa, T., 80 Ogata, Y., 215 Ogilvie, K. K., 142, 146 Ohkatsu, Y., 216 Ohkawa, H., 105 Ohsawa, A., 60 Ohtsuka, E., 99, 145, 152, 154, 155, 156 Oikawa. K.. 152 Oka, H:, 141 Oka, T., 246 Okamoto, Y., 111 Okamura. M.. 190 Okazaki, ’M., ’179

267

Author Index Okazaki, R., 70, 71, 118, 206, 207, 223 Okukado. N., 175 Ong, B. S., 74 Ontshi, H., 152 Ono, Y.,201 Oota. M.. 201 Ootsuka,‘S., 5 Oplatka, A., 152 Oram, R. K., 29, 49, 223, 228 Orgel, L. E., 145 Orwoll, E. F., 201 Osaki, T., 244 Oshima, K., 118, 180 Osman, F. H., 35 Osokin, D. Ya., 236 Ostanina, L. P., 48 Ostoja-Starzewski, K. A., 191 Otera, J., 244 Otsubo, T., 173 Ottinger, R., 232 Ovakimyan, M. Zh., 21 Ovchinnikov, V. V., 255 Overby, L. R., 133 Overman, J. D., 219 Overman, L. E., 219 Oyama, K., 104 Pace, S. C., 225 Paddock, N. L., 72. 194, 203, 250 Padilla, A. G., 20 Paetkau, V. H., 157 Padmanabhan, R., 155,,158 Padolina. M. C.. 15 Padwa, A., 162 . Patzmann, H. H., 186 Pak, V. D., 79 Pantzer. R.. 244 Paquette, L’. A., 165 Park, C. E., 138 Park, J. D., 76 Parry, R. W., 19, 28, 43 44, 51 Parshall, G. W., 44 Parrott, M. J., 212, 239 Parsons, J. T., 157 Pashinkin, A. P., 80 Pashinnik. V. E.. 28 Passmore,‘ J., 61. Patel, P. K., 111 Patel, V. C., 201 Patocka, J., 136 Pattenden, G., 176 Paul, B., 143 Paulsen. H.. 77. 78. 130. 234 Pavelko, T. I., 191 Pavlenko, A. F., 246 Pavlenko, N. G.. 186 Pedersen; E. B., ‘107 Pedersen, L., 221 Peel. J. B.. 42. 254 Peiffer, G.; 104, 224, 231 Penefsky, H. S., 50 Pen’kovzkii, V. V., 239, 247. 249 Pensionerova, G. A., 246 Penusz, H., 258 ~,

9

,

*

,

,

I

Perales, A., 252 Perini, F., 142 Perkinson, W. E., 187 Perregard, J., 107 Perrin, M., 159 Perutz, M. F., 132 Peshchevitskii, B. I., 223 Peterson, D. J., 62 Petrov, A. A., 12, 36, 71, 74, 79, 81, 95, 111, 192 226, 233 Petrov, G., 119 Petrov, K. A., 45 Petrov, L. N., 247 Petrov, M. L., 79 Petrov, S. M., 244 Petrovskii, P. V., 24, 172, 226, 245 Petty, J. D., 106 Pfohl, S., 33 Philip, P. R., 246 Phillips, L., 225 Piekos, A., 120 Pickel, W., 190 Pilyugin, V. S., 244 Pinchuk, A. M., 45, 123, 186. 189 Pinder, J. C., 158 Pinkus, A. G., 57 Plekhanov, V. G., 255 Plenchette. A.. 176 Plieth, K.: 249, 250 Pobedimskii, D. G., 216, 237, 239 Pobiner, H., 54 Pochon, F., 159 Pocker, A., 126 Pogonowski, C. S., 180 Pogorelyi, V. K., 226 Poindexter, E. H., 194 Pokroppa, W., 159 Polezhaeva, N. A., 35, 38, 81 Polikarpov, Yu. M., 65 Pollak, A., 153 Polyachenko, L. N., 175 Polyakova, I. A., 242 Pommerat-Chable, M. F., 88 Poonian, M. S., 155 Porte, A. L., 236 Porter, J. W., 137 Potenza, J. A., 194 Pouet. M.-J.. 72 Poulin, D. ~ ~ ..28. 28, , .227 Poulin. Poulter, C. D:, D., 137 Predvoditelev, D. A., 222 Preston. R. K.. 142 Prikota; T. I., 179 Prinzbach, H., 219 Pronin, I. S., 236 Prons, V. N., 61, 198 Protashchik, V. A., 249 Prout, C. K., 236 PrystXs, M., 138 Pudovik, A. I., 255 Pudovik, A. N., 38, 76, 78, 80,91, 109, 120,121,122, 188, 226, 234, 242, 254, 255,. 257 Pudovik, M. A., 38, 78, 91

Pyrkin, R. I., 46, 1 1 1 Quarrie, S. A., 175 Que, J. R., 223 Quiggle, K., 157 Quin, L. D., 63, 223 Qureshi, A. A,, 137 Rabin, B. R., 125 Rachon, J., 113 Rackwitz D., 221 Rathlein,’K.-H., 71, 169 Raevskii, 0. A., 73, 122, 237, 243 Raigorodskii, I. M., 202 Rajzmann, M., 255 Rakhmankulov, Sh. M., 257 Rakov, A. P., 119 Ramirez F., 27, 33, 35, 39, 50: 83, 97, 123, 252 Randerath, E., 157, 158 Randerath, K., 157, 158 Ranganathan, R. S., 144 Rankin, D. W. H., 44, 231 Rasheed, A., 131 Rasmussen M., 147 Ratcliff, R.’L., 157 Ratcliffe, R. W., 76. 180 Ratovskii, G. V., 236, 243, 246, 247 Rauch, A., 221 Rauk, H. A., 149 Rawlinson, D. J., 108 Razumov, A. I., 48, 55, 56, 58, 74, 95, 100, 226, 245 Razumova, N. A., 36, 81 Razumovskii, S. D., 85 Rebaflca, W., 218 Redjel, A., 178 Redwood, M. E., 222 Rees, R. G., 75 Reese, C. B., 145 Reeve, E. W., 60 Regitz, M., 70, 120, 206 Reichelderfer, R. F., 169 Reines, S. A., 159 Reissbrodt, R., 258 Rejsse, J., 232 Remizov, A. B., 43, 120, 123, 234, 242, 243 Rengaraju, S., 112 Repke, H., 175 Reutov, 0. A., 160 Revel, M., 235 Reynard K. A., 201 Rezvukhh, A. I., 223 Rho. M. K.. 113 252

59,

92,

Author Index

268 Robert, D. U., 28, 54, 59, 229 Roberts, B. P., 52, 208, 210, 211, 212, 214, 239, 240 Robert, J. B., 230 Robins, R. K., 143, 144, 145 Robinson, C. N., 21, 75 Robinson, P. J., 6, 208 Rode, B. M., 42 Rod&, J., 5 Roderick, W. R., 133 Rodriguez, P., 137 Rosch. L.. 2. 52 Roesky, 8.,W., 194, 195, 197, 244 Roesler, G., 144 Rogozhin, S. V., 79, 249 Roisch, U., 133 Romanenko, E. A., 195, 237,244 Romanov, G. V., 255 Romm, I. P., 15, 246, 254 Ronen, H., 6 Rose, I. A., 128, 136 Rose, S. H., 201 Rosenberg, M., 158 Rosenheimer, N., 125 Rosenthal, U., 169 ROSS,B., 189 Rossi, R. A., 109 Rothe, M., 95 Rothuis, R., 18, 21 3, 240 Rottman, F. M., 156 Rozantsev, E. G., 122 Rozinov, V. G., 59, 243 Roznael’skaya, N. A., 15, 254 Rudakova, L. G., 95 Ruden, R. A., 22, 173 Ruterjans, H., 137 Ruppert, I., 39 Rusek, P. E., 240 Rusholme, G. A., 203 Rusina. M. N.. 65 RUSS,C. R., 5,-206 Russell, D. R., 27, 252 Rutherford. J. S.. 251 Ruveda, M: A., 121 Rybicky, J., 201 Rybkina, V. V., 59 Rycroft, D. S., 72, 100, 229 231 Ryl’tskv, E. V., 24, 246 Rymo, L., 157 Ryzhmanov, Yu. M., 238 Saalfrank, R. W., 168, 171 Sabbioni, E., 158 Sabin, J. R., 246 Sadovskii, A. P., 250 Sadykov, A. A,, 223 Sadykov, A. S., 223 Sadykov, M. M., 242 Sadykova, E. M., 246 Saenger, W., 251 Saey, J. C., 257 Safin, I. A., 236 Safonova, T. S., 197 Sahara, H., 201

Saito, H., 189, 197 Saito, M., 201 Saito, T., 189 Saito, Y., 250 Sakata, Y., 173 Sakurai, H., 111 Salakhutdinov, R. A,, 47, 48, 55, 56, 58, 80, 100, 111, 226, 245 Salbaum, H., 166 Saleh, G., 193 Salesi, R. J., 206 Salet, G., 11 Samartseva, S. A., 122,244 Samitov, Yu. Yu., 237 Samiuzzaman, 241 Sammes, P. G., 86 Samokhvalov, G. I., 175 Samuelsson, B. E., 133 Samuni, A., 108,214 Sanchez,.M., 37, 227 Sandmann, H., 3 Sanger, A. R., 228 Sanz, F., 251 Sarbaev, T. G., 87 Sargent, M. V., 173, 174, 177 Sarma, R. H., 221, 235 Sartori, P., 64 Sasaki, M., 105 Sasaki, T., 143 Satchell, D. G., 50 Satge, J., 9, 233 Sato, H., 202 Sato, M., 175, 238 Sato, T., 227 Saudi, S. K., 256 Saukaitis, J. C., 12 Saunders, B. C., 136 Sauter H., 219 Savel’&a N. T., 8 Savichev;, G. A., 245 Savignac, P., 109 Scanu, A. M., 132 Schaap, A. P.,219 Schadow H., 199 Schlfer, ’W., 25, 26, 247, 248 Scharf, D. J., 89 Scheit, K.-H., 151 Scheler, H., 199 Schendel, P. F., 148 Schenetti, L., 234 Scher, M., 130 Scherer H., 70 Scherer: 0.J., 182, 187,192 Scheutzow, D., 222 Schiemenz, G. P., 1, 24, 222 Schipper, P., 17 Schleicher, J. B., 133 Schlemmer, W., 258 Schlimme. E.. 150, 159 Schmid, G., 168 . Schmidbaur, H., 1, 25, 29, 71, 167, 169, 222, 227 Schmidpeter, A., 194, 230 Schmidt, A., 23 Schmidt, W., 244 Schmutzler, R., 27, 29, 42, 61, 183, 233

Schollkopf, U., 121, 180 Schonberg, A., 171 Scholten, M. B., 144 Schott, H., 153, 155 Schroder, R., 121, 180 Schuette, H. R., 175 Schulten, H.-R., 130 Schultz, C. W., 19 Schulz, P., 257 Schulze-Pannier, H., 171 Schumann, H., 2, 52 Schumann, K., 194, 230 Schutz, J., 131 Schwalbe, C. H., 251 Schwarz, W., 114 Schwarzenbach, D., 176 Schweig, A., 26, 247, 248 Schweiger, J. R., 29, 43, 54, 228,248 Schweizer, E. E., 22 Schwendeman, R. H., 42, 43, 246 Scott, G., 216 Sears, C. T., 6 Seawell, P. C., 227 Seconi G., 234 Seide1,’J. C., 241 Seifert, J., 255 Seliger, H., 153 Selve, C., 11, 88 Semashko, V. N., 253 Semin, G. K., 236 Semmler, E. J., 137 Seng, N., 223 Sergeev, G. B., 103 Sergeev, N. M., 232 Sergienko, L. M., 243 Seuleiman, A., 6 Seyden-Penne, J., 178 Seyferth, D., 119, 179 Shabana, R., 76 Shagidullin, R. R., 122, 242, 243,244,245 Shaidulin, S. A., 253 Shakir, N., 13 Shandruk, M. I., 90 Sharov, V. N., 198 Sharpe, W. R., 227 Shatrukov, L. F., 253 Shaver, A., 203 Shaw R A 182 196 197 196 200 ”201 ’202,’ 228: 230: 236,’ 249,’ 250 Shaw, Y. H., 227 Shawl, E. T., 202 Shchennikov, V. S., 56 Shchukina, L. I., 242 Shechter, I., 137 Sheer, M. L., 44, 82. 99 Sheka, Z. A., 66 Sheldrick, W. S., 29, 54, 252 Sheraga, H. A., 137 Shermergorn, I. M., 243 Shevchenko, M. V., 189 Shevchenko, V. I., 186,197 Shevchuk, M. I., 16, 173, 245 Shibaev, V. N., 128, 129 Shigyo, H., 154 Shih, L. S., 30

269

A uthor Index Shiiov, I. V., 226 Shimada, Y.,97, 141 Shipkowitz, N. L., 133 Shirafuji, T 118, 180 Shizhko, V:’S., 202 Shokol, V. A., 76, 88, 183, 186, 189, 242,244 Shtepanek, A. S., 191 Shtil’man, S. E., 120, 226, 234 Shugar, D., 156 Shukla, R. J., 80 Shuman, D. A., 144, 145 Shurubura, A. K., 239 Shvetsov-ShiDvskii. N. I.. 249 Siddall, J. H., 223 Sidky, M. M., 35, 76, 85, .

I

21 5

Sidoikin, V. F., 244 Sidwell, R. W., 144 Sieker. L. C.. 128 Siess, 8. A., 126 Simalty, M., 69 Simon, L. N., 144, 145 Simon. 2.. 15 Simoncsits, A., 153 Simonnin, M.-P., 72, 232 Simonson, L. P., 150 Singer, E., 171 Sinitsa, A. D., 61 Singer, M. I. C., 13 Singleton, R., jun., 124,128 Sinyavskaya, E. I., 66 Sisido, K., 18 Sisler, H. H., 51 Sizova, M. V., 46 Skaletz, D. H., 5 Skolnik, E. G., 206 Skorovarov, D. I., 201 Skowronska, A., 13 Skvortsov. N. K.. 71. 226 Skzypczynski, Z.; 96 Slein, M. W., 129 Slijko, F. L., 225 Slodki, M. E., 130 Slota, P. J., 44 Slotin, L. A., 142 Smith, B. C., 196, 200. 230 Smith. D. A.. 157 Smith: D. J.’ H., 67, 187, 223 Smith, G. D., 123 Smith, M., 155 Smith, S. L., 221 Smoot, J., 219 Smrt, J., 98, 143, 54, 156 Snell, G. W., 129 Snieckus, V., 173 Snoble, K. A. J., 61, 224 Snyder, J. P., 168 Sochilin. E. G.. 5 So11, D.; 158 ’ Smensen, S., 224, 231 Soifer, G. B., 55, 189, 237 Soimu. P.. 257 Sokalskaya, L. I., 122 Sokoloski, E. A., 132 Sokolov, M. P., 226, 245 Soliman, F. M., 76 Solleder, G. B., 14

Solodovnikov, S. P., 239 Solomon, P. W., 13, 66, 216 Solter, L. E., 106 Soma, N., 17 Sommer, H., 153 Sondheimer, F., 177 Songstad J., 14 Sorm, F.: 138 Soroka, M., 113 Sorokina, S. F., 222 Sorokina, T. D., 76 Sosnovsky, G., 108, 122 Soulen, R. I., 166 Sowerby, D. B., 195, 196 Spadari, S., 158 Spence, G., 135 Spencer, T. A., 22 Spiro, T. G., 54 Splitter, J. S., 14 Sprinzl, M., 142, 157, 159 Staab, H. A., 218 Stadelmann, W., 233 Staendeke, H., 44 Stahl, K.-W., 15 Stafforst, D., 121, 180 Staneloni, R. J., 131 Stangeland, L. J., 14 Stanishevskii, L. S., 179 Start. G. R.. 126 Startevan, J: M., 257 Stec, W. J., 117 Steckel, T. F., 60 Stein, M. T.. 202, 252 Steinman. G.. 128 Stelzer, O., 233 Stepanov, B. I., 2, 15, 191, 198,230,239,247,254 Stephana, R., I75 Stern, P., 39, 83, 97, 123, 252 Sternbach, H., 142 Stevens, J. D., 144 Stevens, R. L., 87 Stewart, W. E., 223 Stillwell, W., 128 Stockdale, B. R., 57 Stocks, R. C., 63, 223 Straub, K. D., 134 Strauzhan. B. P.. 243 Street&, D. G., 143 Strick, A,, 28, 53, 228 Strickland, R. C., 165 Struck, R. F., 107, 139, 140 Struchkov, Yu. J., 249,250 Stuart, S. E., 156 Stuhler, H., 29, 167, 227 Stiitz. A,. 151 Sturtevant, J. M., 101 Sturtz, G., 109, 179 Suck, D., 251 Sudakova, T. M., 121 Sudarev, Yu. I., 80 Suerbaev, Kh. A., 24, 172, 245 Sugiura, K., 139 Sugiyama, T., 154 Suh, B., 135 Sukhorukov, E. I., 242 Sukhorukova, N. A., 247 Sultanova, D. B., 48

Sultanova, R. B., 80 Sunamoto, J., 102,225,226 Sundaralingam, M., 251 Sundler, R., 258 Supin, G. S., 110 Suschitsky, H., 77 Suskina, V. I., 122 Sutton, J., 106, 215 Suzuki, A., 139 Suzuki, Y..241 Symons, M. C. R., 55, 122, 209, 215, 238 Syrneva, L. P., 95 Szab6, P., 129 Szeto, K. S., 158 Tachpulatov, Yu. T., 242 Taddei, F.,234 Taguchi, S., 59 Takagi, H., 17 Takahashi, T., 217 Takaku, H., 97, 141 Takamizawa, A., 107, 139, 140 Tamm, L. A., 12, 95 Tamura, M., 18 Tan, H.-W., 93, 235 Tanaka, Y.,22, 172 Tang, Y.-N., 54 Tani, K., 5 Tarasevich, A. S., 221,222, 253 Tashma, Z., 256 Tate, M. E. 132 Taylor, D. A., 175 Taylor, E. C., 173 Taylor, M. J., 142 Taylor, M. V., 86 Taylor, R. C., 4 Taylor, W. G., 142 Tazawa, I., 156 Tazawa, S., 156 Tebbe, K. F., 250 Tegg, D., 144 Teichmann, H., 16 Telegin, G., 201 Telkova, I. B., 199, 230 Teranishi, S., 15 Terauds, K., 42, 254 Terenmeva, T. V., 55 Terent’eva, S. A., 38, 78 Tereshchenko, G. F., 71, 226 Tewari, R. S., 80 Tezuka, T., 142 Tidwell, T. T., 104 Tikhonina. N. A.. 38 Tille, H., 4 Timakova, L. M., 65 Timmer, E. C., 107 Timmler, H., 223 Timofeeva T. V 250 Tirnokhin,’B. V.i’236, 243, 246 Tishchenko, J. G., 179 Titov, A. I., 46 Thalacker, R., 192 Thamm, R.,8 The, K. I., 28, 227 Thenn, W., 30, 81, I86 Thierfelder, W., 16

Author Index

270 Thiem, J., 77, 130 Thomas, G. J. jun., 159 Thomas, J. M., 248 Thomas, M. G., 19 Thompson, J. C., 137 Thorpe, M. C., 107, 140 Thomas, R., 178 Thoumas, A., 122, 226 Thozet, H., 258 Thynne, J. C. J., 44 Tobias, L., 155 Tochino, Y., 139 Todd, J. F. J., 256 Tolls, E., 53 Tolman, R. L.. 144 Tomasz; J., 153 Tom Dieck, H., 191 Tomioka, H., 63, 71, 204, 207 Tomlinson, A. J., 28. 227. 228 Tonnard, F., 88 Tonomura. Y.. 135. 152 Torgasheva, M.A.,' 110 Torrence, P. F., 156 Tosa, T., 126 Toscano, V. G., 204 Toube, T. P., 176 Tozuka, Z., 173 Tran, D. Z., 229 Tret'yakova, A. Ya., 256 Triantaphylides, C., 104 Trimm, J. R., 258 Trindle, C., 161 Trippett, S.. 27, 29, 31, 33, 49, 85, 223, 228. 252 Troitskii, M. F., 129 Tronchet, J. M. J., 176 Trotter, J., 72, 203 Trus. B.. 15 T s a i Y-G., 105 Tsentovskii, V. M., 256 Tsivunin, V. S., 48, 80 T'so. P. 0. P.. 156.221.225 Tsuchida, E.,' 201' ' Tsuji, H., 156 Tsvetkov. E. N... 72., 237 Tu, C. D:, 155 Tucker, P. A., 251 Tudrii. G. A.. 36. 81 Tukhar,-A. A., 191, 247 Tul'chinskii, V. M., 81 Tunemoto, D., 180 Turczak, J., 83 Turley, P. C., 114 Turnblom. E. W.. 32, 205 Turyn, D.; 102 Tuzova, L. L., 252 Tyssee, D. A., 114 Tyvorskii, V. I., 179 -

,

~

~~

Ubasawa, M., 155 Uchida, K., 50 Ugi, I., 27, 33, 35, 97 Utimoto, K., 18 Vachugova, L. I., 122,244, 245 Vakhrusheva, N. N., 243 Valadon, L. R. G., 176 Valenzuela, P., 126

Valetdinov, R. K., 8 Valitova, F. G., 238 van Boom, J. H., 145 Van de Grampel, J. C., 193 Van der Holst, J. P. J., 115 Van der Steen, J., 107 van de Sande, J. H., 158 Van de Vorst, A., 241 van Dijk, J. M. F., 213 Van Hooidonk, C., 115 Van Wazer, J. R., 51, 184, 221, 226, 235 Vashman, A. A., 236 Vasyanina, M. A., 66 Vaultier, M., 169 Vecchia, L. D., 175 Vedejs, E., 68, 161, 162, 224 Veillard, A., 28, 53, 228 Veits, Yu. A., 4,49,94,222 Velinov, I., 119 Venegas, A., 126 Vereshchaain. A. N.. 43. 237, 254Verkade, J. G., 93, 123 Verkade, W. R., 227 Verlander, M. S., 145 Vermeer. H.. 26. 247. 255 Vesper, i,3' ' ' Vigalok, I. V., 47, 111 Vigdergauz, M. S., 257 Vilceanu, R., 15, 257 Vincent, E. J., 231 Vines, S. M., 13, 86, 219 Vinogradova, V. S., 38, 76, 87, 217 Vivarelli, P., 234 Vizel, A. O., 48, 223, 242 Vlattas, I., 175 Vogel, P., 173 Voigt, D., 55, 249 Volkovitskii, V. N., 32, 49, 65 Voll, U., 171 Vollhardt, K. P. C., 177 Volodin, A. A., 199, 230 Voncken, W. G., 31, 36, 215 von der Haar, F., 159 von Dobeln, U., 150 Von Esch, A. M., 133 von Malotki, P., 3 Vorbruggen, H., 107 Vorkunova, E. I., 237 Voronkov, M. G., 80, 244 Voronovich. N. S.. 247 Vostrowsky; O., 176 Votruba, I., 142 Vul'fson, S. G., 43, 254 I

,

Waclawek, W., 122 Wadsworth, W. S., 105, 25 1 Wagner, G., 247 Wagner, P., 251 Wakabayashi, N., 60 Walach, P., 5 Walker, B. J., 16, 79, 87 Walters, D. B., 4 Walters, R. M., 60 Wannagat, U., 185

Warnecke, H.-U., 179 Warning, K., 11, 61 Warren, C. D., 130, 131 Warren, S. G., 69, 70 Wasielewski, C., 113 Watanabe, Y., 41, 106 Watenpaugh, K., 128 Waters, J. A., 156 Watts, P. H. jun., 171, 248 Weavers, R. T., 177 Webb, S. B., 225 Webster K., 238 Weedon: B. C. L., 176 Weekes, J. E., 75 Weidlein, J., 227 Weiss, R. G., 204 Weissmann, C., 157 Weitl, F. L., 19, 47 Welch, M. H., 135, 136 Welch, S. C., 15 Wells, D. V., 114 Wells, R. D., 148 Welter, W., 120, 206 Werber, M. M., 152 Werstuik, E. S., 155 West, B. O., 222 Westheimer, F. H., 29, 101, 135, 257 Westra, J. G., 107 Westwood, J. H., 130 Wetzel, R. B., 63 Wheeler, G. L., 171, 248 W k m , D. J., 215, 239, White, A. J., 200 White, D. A., 6 White, H. A., 147 White, M. W., 31 White. R. F. M.. 100 Whitham, G. H.; 9, 68 Whittle, P. J., 31, 33, 85, 228

Wieber, M., 27, 35, 41, 44, 91, 233 Wieland, 0. H., 126 Wiezer. H.. 197 Wightman,' R. H., 99, 156 Wilfinger, H.-J., 32 Wilkes, J. S., 151 Willard, J. M., 128 Williams, D. L., 157 Williams, F., 238 Williams, J. K., 47, 228, 24 1 Willick. G. E.. 152 Willie, G. R., '223 Willy, W. E., 165 Wilson, I. B., 136 Wins. P.. 136 Witkop, 'B., 156 Witkowski, J. T., 143 Witt, J. D., 54 Wittig, G., 160 Woenckhans, C., 124 Wolf, R., 37, 39, 40, 227 Wolfenden, R., 135 Wolfsber~er.W. I.. 190 Wolfson,-J. 'M., 159 Wolring, G. Z., 137 Wood, D. J., 221, 235 Wood, H. C. S., 57

27 1

Author Index Wood, H. G., 128 Wood, T., 128 Woodis, T. C., 258 Woods, M., 196, 199, 200, 228, 230, 249, 250 Worthington, P. A., 225 Wrixon, A. D., 125 Wu, R., 155, 158 Wuest, H., 162 Wunderlich, H., 27 Yagfarov, M. Sh., 257 Yagudeev, T. A., 87 Yakutina, 0. A., 243 Yamada, E. W., 135 Yamada, S., 135 Yamaguchi, A., 179 Yamaguchi, H., 202 Yamaguchi, M., 175 Yamamoto, H., 118, 180 Yamomoto, T., 135 Yamashita, H., 139, 215 Yamashita, M., 215 Yamauchi, K., 111 Yamazaki, N., 91 Yanchuk, N. I., 90 Yanik, B., 199 Yarkova, E. G., 243 Yaroshenko, G. F., 65 Yaroshenko, N. A., 257 Yashkin, V. V., 122

Yastrebova, G. E., 76 Yastremskaya, N. V., 78 Yato, T., 234 Yatsimirskii, K. B., 66 Yegian, C. D., 258 Yoke, J. T., 55 Yoneda, S., 171, 231, 234 Yoshida, Y., 41, 106 Yoshida. Z., 171. 231. 234 Yoshie, R.,202 ' Yoshifuji, M., 70, 71, 118, 207, 223 Yoshii, E., 41, 98, 106 Young, J. H., 149, 133 Youssef, A.-H., 57 Yvernault, T., 104 Yuldashev, A., 242 Yurchenko. R. I.. 191. 247 Yurchenko; V. 'G., ' 191, 247 Yusupova, T. N., 257 Zaeske, P.. 250 Zagurskaya, L. M., 14, 229, 255 Zakharov, IS. S., 14, 229 Zakharov, V. I., 111, 233 Zamaletdinova. G. U.. 76 Zamojski, A., 83 Zapirov, S. I., 8

Zaripov, N. M., 252, 253 Zarkadas, A., 3, 52, 53 Zasorina, V. A., 191 Zatorski, A., 75, 114, 179 Zavalishina, A. I., 8 1, 222 Zavarikhina, G. B., 242 Zavlin, P. N., 91 Zav'yalov, A. P., 253 Zawadzki. S.. 110 Zdero, C.; 162 Zefirov, N. S., 7 Zeleneva, T. P., 198, 230 Zerba, E. N., 121 Zhadanov. B. V.. 242 Zheshutko, V., 199 Zhmurova, I. N., 191, 239, 247 Ziehn, K: D., 11, 61 Zimmermann, D., 232 Zink J. I., 172, 205 Zolofareva, L. A., 191,247 Zoroastrova, V. M., 36, 81 Zschunke, A., 222, 232 Zukin, R. S., 137 Zumbulyadis, N., 194 Zumwald, J.-B., 176 Zwierzak, A., 110 Zyablikova, T. A., 48 Zykova, T. V., 47, 48, 56, 55, 58, 59, 80, 100, 111, 226, 245