SOJIE HETEBOCYCLIC COMPOUNDS OP NITROGER, PHOSPHOBUS AID ARSENIC

By R.A. Earley, B.Sc.

Tbis Thesis is submitted in fulfilment of tbe requirements fer the degree of Master of Science.

Superviaor: Dr. K.J. Gallagher, Department of Organic Chemistry, School of Chemistry, The University ot New South Wales.

Pebruary 1969. i '- . .. / '--~~- PREFACE

The work described in this thesis was carried out in the Organic Chemistry Laboratories at The University ot New South Wales from February 1967 to Pebruar;y 1969, under the supervision of Dr. K.J. Gallagher. It is original except in those parts ao indicated. !hie thesis has not been submitted tor a higher degree at a.n.r other university.

R.A. Earley. (1)

!ABLE OP COMD!S

Pase• W ABSTRACT (111) SECTI01' 1. THE 1'.K.R., ULTRAVIOLE! AND MASS SPECTRAL PROPER!IES 01 SOME PBENARSAZINE DERIVATIVES AND BELA!ED COKPOUimS. 1 .1 Introduction 1 Resulte and Discussion 1.2 Preparative Chemistry 10 1. 3 N.:M.R. Spectra 28 1 .4 Ultraviolet Spectra 34 1 .5 Mass Spectra 38 1. 6 Experimental Section 51

SECTION 2. SYNTHESIS OP HE!EROCYCLES WITH A STEREOCH!J1ICALLY RIGID HE'.rEBO A!O:M

2.1 Introduction 77 2.2 Result• and Discussion 84 2.3 Experimental Section 101

SECTION J• lfEW APPBOACHES TO 10-SUllSTITUTED- 5,10-DIHYDROPHDOPHOSPBAZIIIES 3.1 Introduction 112 3.2 Results and Diecuasion 117 3.3 Experimental Section. 123 (11)

!ABLE OP CONTENTS (contimled) Page Bo

SECTION 4. THE WITTIG REACTION WITH HE!EROCYCLIC PBOSPHOBIUM SALTS 4.1 Introduction 128

4.2 Results and Discussion 133 4.3 Experillental Section 140

REPERERCES 146

ACDOWLEDGEMEITS 152 (111)

The ~.M.R., u.ltraTiolet and mass spectral properties or aoae pbenaraazine derivatives baTe been studied. A aeries er related compounds bas been prepared,an.d strong evidence bas been presented which suggests that d~-p~ bonding occurs in the metbiodides or 10-substi'tuted dibydropbenareazines. The novel beteroc1c1e,azarsatr7PtyceneJbas been prepared and a number or its reactions have been studied. Several new approaches to 10-substituted-5,10- dibydropbenophosphazines are described. The use of beterocyclic pbosphonium salts in the Wittig reaction has been studied. Attempts to develop a usetu.l unsymmetrical diene synthesis using these salts ia described. ,..,,:.::-...,11 .. •tit / ;' I • \~· --.:: ..... s,,.,..oT SECTION I \ . '---...... _ C •·~Af'

THE N.r.1.R., ULTRAVIOLET AND MASS SPECTRAL PROPERTIES OF SOME PHENARSAZINE DERIVATIVES AND RELATED COMPOUNDS

1 .1 Introduction Arsenic trichloride reacts with diphenylamine to give 10-chloro-5,10-dihydrophenarsazine (I) in quantitative yield. 1

(I) This reaction, which was developed independently in several centres during World War I, was extensively investigated in subsequent years. 2 The reaction fails if a tertiary amine is used or if a substituted haloarsine is employed. Thus it was found3 that when N-methyldiphenylamine was reacted with arsenic trichloride, the only product isolated was (I) in low yield, obtained presumably through demethylation of the amine and subsequent reaction of the diphenylamine produced. - 2 -

10-Chloro-5,10-dihydrophenarsazine was also isolated in low yield, together with a small amount of benzene, when phenyldichloroarsine was reacted with diphenylamine. 4 No other products were obtained and the mechanism suggested involved disproportionation of the phenyldichloroarsine to give arsenic trichloride and benzene.

2PhAsC1 2 ) Ph 2AsCl + AsCl 3 AsC1 3 + Ph 2NH ) (I) + 2HC1 HCl + Ph 2AsCl ) PhAsC1 2 + PhH

These results led to the suggestion5 that the mechanism of the reaction between arsenic trichloride and diphenylamine involves as a first step, the formation of species (II), which then rearranges intramolecularly or reacts with another molecule of diphenylamine.

(II) While 10-substituted dihydrophenarsazines cannot be prepared directly, they can be prepared by the reaction of (IJ with Grignard reagents. 6 The resulting tertiary arsines (III) react with methyl iodide to form quaternary arsonium methiodides (IVJ. - 3 -

(l)

(III) (IV) In the course of a synthetic investigation (reported in Section 2) the N.M.R. spectra of several 10-substituted- 5,10-dihydrophenaxsazines and their methiodides were determined. Table 1 shows the position of the NH proton signal in the N.M.R. spectrum of three phenaxsazines and their methiodides.

TABLE 1 NH Proton Signal (b)*in a Series of 10-R-5,10-Dihydrophenaxsazines and Their Methiodides

R Arsine Salt t:, b Ref. o-Chlorophenyl 6.27 10.43 4.16 This study p. Phenyl 6 .17 10.40 4-23 6 Methyl 6.23 10. 35 4-12 6

* In ppm downfield of TMS in cnc1 3 except 10, 10-dimethyl- 5,10-dihydrophenazaxsonium iodide which was run in - 4 -

In each case the shift of the NH proton observed on quaternisation was approximately 4 ppm downfield, which seemed far greater than would be expected on electrostatic grounds alone. For example, quaternisation of the phosphorus atom of a tertiary phosphine results in a downfield shift of the N.M.R. spectrum which varies from .2,g. 1.5 ppm for the protons a to phosphorus to only~- 0.1 ppm for the Y protons. 7 Some form of interaction of the nitrogen lone pair with the contracted 4d orbitals on the quaternary arsenic atom, to eive resonance structures such as (V), could be contrib­ uting in the phen~rsazine methiodides.

CIV) ...<_..,.,

( V) Such a delocali8~tion of the positive charge over the ring could account for the downfield shift of the NH proton in the N.M.R. spectrum of the quaternary methiodides. The NH proton signal in pyrrole, for example, is at b7.538 compared to b1.5-1.8 in pyrrolidine; 9 this shift being due to aromatisation of the ring system. If the deloctlisation suggested by (V) was the case, - 5 - then the phenarsazine methiodides would provide a further exam:ple of d -n bonding, which is believed to occur in '11: - '11: several other classes of organometallic compounds of the group V elements. It should be noted here that represent­ ation of d'11:-p'11: bonding by resonance structures such as (V) is an oversimplification of this type of~ bonding and presents an inaccurate picture. However, it is the only representation which is readily depicted and this inadequacy should be borne in mind when structure (V) is referred to throughout this Section. Involvement of the nitrogen lone pair in the bonding of (I) has been suggested to account for some of the anomalous properties of that compound. Early workers noted the intense yellow colour of (I), its high melting point, and low solubility in most organic solvents. When compared with 10-substituted-5,10-dihydrophenarsazines (III), which are colourless, and chloroarsines, which are usually readily soluble in organic solvents, (I) seemed in contrast, to possess physical properties similar to a salt, though its chemical properties were those of a chloroarsine. The anomalous properties of (IJ led the early workers to suggest several possible resonance structures (VI, VII, VIII) for (I), 1, 10 , 11 which in effect meant some delocalisation of the nitrogen lone pair over the ring system. - 6 -

+~ ) ©(00 Cl-

( VI) ( VII) !

Cl - OGD+~ h H

( VIII) A recent X-ray crystallographic study of (I) by Cameran and Trotter12 showed that the As-C bonds (1.917 + 0.007 j) are significantly shorter than the normal As-C single bond distance,, [e.g. 1.99 ± 0.019 i in cacodyl sulphide (IX)] and the C-N-C angle of 128° is larger than normal.

(CH 3) 2AsSAs(CH 3) 2 (IX) Cameran and Trotter concluded that "these features suggest an extended aromatic system in phenarsazine chloride (I), involving interaction of the arsenic and nitrogen lone

pairs with the o-phenylene ~ electrons, with in addition possible ¾-P~ bonding between the~ electrons and the vacant - 7 -

4d orbitals of the arsenic atom". 12 The type of interaction suggested in the methiodides of the phena.rsazine derivatives also bears some similarities to the bonding in the phosphazene series, of which the cyclic trimeric compound (XJ is a typical member.

( X) There has been considerable conjecture as to the nature of the bonding in this class of compounds. One school of thought 13 maintains that "pseudoa.romatici ty" exists in this series of compounds and that continuous overlap of the~ electron system a.round the ring is possible, using the 3d orbitals of phosphorus, conferring aromatic character on the system. The other schoo1 14 maintains that because of orbital symmetry considerations it is not possible to obtain continu­ ous overlap except in special cases, the~ electron system being interrupted at each phosphorus atom in most phosphazene compounds. This theory considers that the~ electron system is restricted to "islands of aromatic character" interrupted at each phosphorus atom. Chemical and physical evidence is inconclusive and both theories a.re currently held. - 8 -

In a recent paper, 15 Aguiar et al. reported evidence of d~-p~ bonding in a group of heterocyclic phosphonium salts. The 31P N.M.R. spectrum of (XI) gave a signal for the phosphorus atom at +3-5 ppm, relative to 85% phosphoric acid.

28r

(XI) This was the first phosphonium salt reported to have a positive 31 P N.M.R. shift, the usual value being .Qa• -20 to -30 ppm. This large shielding effect led Aguiar --et al. to suggest that a 4~ aromatic system, involving overlap of the~ electrons with the contracted d orbitals on phosphorus, was present. These examples bear obvious similarities to the type of behaviour suggested by the N.M.R. spectra of the phen­ arsazines and their methiodides. To investigate the extent of this effect in the phenarsazine series it was decided to prepare a series of arsenic-nitrogen and related compounds in which the possibilities for the type of conjugation suggested in structure (V) were of differing magnitude, i.e. - 9 -

pathways and path where different possible conjugation N.I.1.R., ultraviolet lengths were present and to study their and mass spectral properties. - 10 -

RESULTS AND DISCUSSION

1.2 Preparative Chemistry With the exception of the o-chlorophenyl compound (XII; and its derivatives, the phenarsazines used in this study 6 16 were known compounds. ' 10-(o-Chlorophenyl)-5,10-dihydro- phenarsazine (XII) was prepared in 76% yield by the reaction of (IJ with o-chlorophenylmagnesium bromide. The arsine oxide (XIV) was prepared by the conversion of the arsine to the diiodide (XIII J with alcoholic iodine, followed by hydrolysis and dehydration. OC©J 0~ ~ c1-Q/ (XII) (XIII) (XIV) Mann et al. 17 prepared a seven-membered ring heterocycle (XV) by the reaction of 2,2'-dilithiodibenzyl with phenyldichloroarsine. - 11 -

It was thought that treatment of the 2,2'-dilithio compound from N-(o-bromobenzyl)-o-bromoaniline (XVI; with phenyldichloroa.rsine would produce a seven-membered ring arsenic-nitrogen heterocycle (XVII).

~ i>BuLj ©()QJ ii)PhAsCl2 As I Ph

(XVI) (XVII) Such a compound would provide a shorter possible conjugation pathway than in the phena.rsazines themselves, and the methiodide of this heterocycle would be expected to exhibit a smaller downfield N.M.R. shift of the NH proton relative to the NH position in the arsine, if the type of d~-p~ bonding suggested in structure (V) was operating. Reaction of o-bromobenzyl bromide with o-bromoaniline gave (XVI) in 67% yield. Carboxylation experiments were carried out to determine the optimum conditions for

lithiation. When 2.7 moles of n-butyl lithium-N,N,N 1 ,N 1 - tetramethylethylenediamine, a powerful metallating agent, 18 was added to (XVI), followed by treatment with solid carbon dioxide, a 53% yield of a monocarboxylic acid was obtained. The N.M.R. spectrum of the methyl ester of this acid showed - 12 -

a broad NH singlet at b 4-91, suggesting that lithiation had occurred on the phenyl ring attached to the benzyl group to give (XVIII).

(XVIII) If lithiation had occurred on the phenyl ring attached to the amine group to give (XIX), then the NH proton signal would be expected to be further down.field due to deshielding b,r the ortho carboxyl group.

Br ~ eOO:©J

(XIX) This was later confirmed when (XIX) was synthesised by an unequivocal route, by the reaction of methyl anthranilate with o-bromobenzyl bromide. The NH proton signal in the N.M.R. of (XIXJ appeared at o 8. 24. - 13 -

(XIX)

When 5.8 moles of n-butyl lithium-diamine complex was reacted with (XVI), followed by carboxylation, an 89% yield of the dicarboxylic acid (XX;, was obtained.

(XX) When the 2,2'-dilithiobenzylaniline was treated with phenyldichloroarsine, the seven-membered ring heterocycle (XVIIJ was obtained in low yield after vacuum distillation of the product and chromatography.

A large amount of a sticky insoluble gum was precipi­ tated when the phenyldichloroarsine was added to the dilithiobenzylaniline. This material was insoluble in water and most organic solvents and was probably a complex mixture of polymerisation products, obtained through the formation of As-N bonds. Such products would be readily formed since lithiation of (XVIJ results not only in lithiation of the - 14 - phenyl groups, but also in N-lithiation. Treatment of this insoluble material with ethanolic hydrogen chloride, followed by digestion with ethanol­ chloroform (1:1), left an insoluble crystalline solid shown to be N,N,N',N'-tetramethylethylenediamine bishydrochloride. Chromatography of the organic solubles on alumina gave a low yield of a crystalline arsine, isomeric with the previously isolated seven-membered ring heterocycle (XVII;. The infrared spectrum of this arsine showed no NH absorption. The N.M.R. spectrum showed an AB quartet at o 4. 9 3 and an aromatic multiplet at o 7. 28. The ratio of the two signals was 1:7. The mass spectrum showed a parent ion at m;e 333 and elemental analysis was satisfactory for c19tt 16NAs. The compound was hence the azarsoline (XXI), which arises presumably through ring closure by reaction with the N-lithio group rather than with the aryl lithio group. ©Ct?~o t{Nv,~ Ph Li Ph (XXIaJ (XXI1 It is not clear why this arsine was present in the insoluble polymeric material and not in the organic solubles. It is possible that some complex is formed by intermediate (XXIa) which rend-9rs the product insoluble. - 15 -

2-Arr.i r:oethyl pho sp~~-re s have been prepared in high yield by the reaction of aziridine with lithium dipher..yl­ phosphine. 19 Treatment of N-phenylaziridine with lithium diphenylarsenide should also cause cleavage of the aziridir.e ring to give, on hydrolysis, a 2-aminoethylarsine (XXII).

(XXII) (XXIII)

Quaternisation of such an arsine would give an arsonium salt (XXIII) in which there was no possibility for conjugation of the type suggested for the phenarsazine methiodides by structure (V). Thus there should be no marked downfield shift of the NH proton in the N.M.R. spectrum on quaternis­ ation of (XXII), if as suggested, d~-p~ bonding is responsible for the shifts in the phenarsazine methiodides. 2-(N-Phenylamino)ethyldiphenylarsine (XXII) was prepared in 66% yield by this route. However, treatment of the arsine vii th methyl iodide failed to produce the arsoniu □ iodide (XXIIIJ. A mixture of products was formed which could not be separated. The N.M.R. spectrum of the crude mixture showed four singlets in the region 02.5-3-2, suggesting that N-methylation was proceeding at a rate competitive with quaternisation of the arsenic atom. No such problem arose with the analogous phosphorus - 16 - compound, prepared by the action of lithium diphenylphos­ phide on N-phenylaziridine. The methiodide was readily prepared. Arsenic quaternises at a relatively slow rate compared to phosphorus, 20 (several hours reflux with methyl iodide often being required), and it is perhaps not unexpected that N-methylation of the secondary amine proceeds at a competi­ tive rate. Several attempts were made to prepare the desired quaternary arsonium methiodide (XXIII). No suitable protecting group could be found which would survive quater­ nisation and could then be removed without destroying the quaternary centre. A p-toluenesulphona.mide was prepared which seemed to survive quaternisation, but the vigorous conditions required to hydrolyse the sulphonamide group destroyed the quaternary centre. An attempt to quaternise triphenylarsine with 2-bromo­ ethylaniline hydrobromide (XXIV) failed to produce a quaternary salt, even after prolonged reflux in benzene.

PhNHCH 2CH 2Br.HBr ( XXIV) The benzylamino arsine (XXV) was proposed as an alternative arsine containing a saturated centre between the nitrogen and arsenic atoms. - 17 -

(XXV) o-Bromobenzylaniline (XXVI) was prepared by reaction of aniline with o-bromobenzyl bromide. An 8% yield of bis-N-(o-bromobenzyl)aniline was also obtained in this reaction. Treatment of (XXVI) with lithium diphenylarsenide failed to produce (XXV). Benzylaniline was isolated, suggesting that a halogen-metal interchange had occurred in the reaction.

CXXVI)

The tetraphenyldiarsine postulated as the by-product was not isol8.ted. The diarsine is readily oxidised to diphenyla.rsinic acid 2nd the arsine oxide 21 and, if present, it would have been oxidised to these products during workup. There have been several instances of halogen-metal interchange reactions of this type reported in the literature, - 18 - though the factors governing this type of reaction are not fully understood. Beeby et al. 22 isolated a 40% yield of phenyldichloroarsine when they reacted phenyl~sinebis­ (magnesium bromide) with o-xylylene dichloride in a prepar­ ation of the isoarsindoline ring system (XXVII).

Ph +PhAsCti

(XXVII) They suggested a halogen-metal interchange to account for this reaction.

When phenylarsinebis(magnesium bromide) was reacted with ethylene dibromide, a high yield of arsenobenzene (XXVIII) was obtained. 23

PhAs(MgBr) 2 + BrCH 2CH 2Br ~ (Ph-As=As-Ph)n (XXVIII) A similar reaction of potassium diphenylarsenide with ethylene dibromide gave ethylene and tetraphenyldiarsine. 24 When diphenylchloroarsine was added to o-lithiobenzyl­ aniline, the desired arsine (XXV) was obtained in 28% yield. - 19 -

Attempted quaternisation of this arsine also gave a mixture of arsonium salts; N-methylation again presumably being a competing reaction. It is perhaps not unexpected that N-methylation is a competing reaction with this arsine since the benzylamino group is particularly reactive. It is however surprising, in view of this result, that the quaternisation of the seven-membered ring heterocycle (XVII) proceeded without any sign of N-methylation, since it also contained a benzylamino group. The concept of inductive deactivation, introduced by Menn, could be invoked to explain this apparent anomaly. Mann prepared a number of tertiary arsines and phosphines which could not be quaternised or which required forcing conditions for quaternisation. 25, 26 Thus o-phenylenebisdimethylarsine (XXIX) only forms a monomethiodide when refluxed with methyl iodide. 25

(XXIX) The dimethiodide can be prepared by heating the diarsine with methyl iodide in a sealed tube at 100° for several hours, Mann explained these results by suggesting that the development of one quaternary centre deactivated the - 20 - adjacent terti8.ry centre and m8de quaternisation of the second centre difficult. It is possible that the development of a quaternary centre at the arsenic atom in the seven-membered ring heterocycle (XVII) results in deactivation of the adjacent amino group and retards N-methylation. No such deactivation

can occur in the benzyl arsine (X:XV) and hence N-methylation is a competing reaction. (X:XXJ was also proposed as a suitable alternative arsine with a saturated centre between the arsenic and nitrogen atoms. In this case quaternisation of the benzylic arsine group would be expected to occur at a far more rapid rate than N-methylation of the diphenylamino group.

(XXX) It was proposed to form (o-bromobenzyl)diphenylarsine (XXXIJ first, and then to react this arsine with aniline to give ( XXXJ .

(XXX)

(XXXI) - 21 -

The PYI'Olysis of a.rsonium salts is a well known route to terti:i.ry arsines, the most labile alkyl group usually being expelled t~ give the alkyl halide and the tertiary arsine. 27 (o-Bromobenzyl)diphenylmethylarsonium bromide (XXXII) was prepared in high yield from o-bromobenzyl bromide and diphenylmethylarsine.

(XXXII) Pyrolysis of this salt was expected to give methyl bromide and (XXXI). When the pyrolysis was carried out, however, o-bromobenzyl bromide was eliminated and the distillate, on standing, gave the starting salt (XXXII), the o-bromobenzyl bromide and diphenylmethylarsine distilling at about the same temperature. Several previous cases of these types of pyrolyses proceeding by an unexpected route have been reported. (XXXIII;, for example, did not eliminate methyl bromide as expected, but gave phenyldimethylarsine and 4-bromobutyro­ nitrile.28 This route was not pursued.

Me I + Phf s CH 2CH 2CH 2CN Me (XXXIII) - 22 -

A suitable arsonium salt was finally prepared directly, by the reaction of 2-iodoethylaniline hydriodide with phenyldimethylarsine. 2-Iodoethylaniline hydriodide was prepared by the acti~n of hydriodic acid on N-phenylethan­ olamine. Prolonged reflux of this hydriodide with phenyldimethylarsine in methanol gave a low yield of 2-(N-phenylarnino)ethylphenyldimethylarsonium iodide (XXXIV) after workup. Me I PhAs+cH2CH2NHPh I- I Me (XXXIV)

This salt is closely related to the 2-aminoethyl arsine (XXII; which was previously prepared, though its parent arsine has a methyl group in place of one of the phenyl groups in (XXII). 2-N',N'-Dimethylaminodiphenylamine (IlXV) was prepared to provide a compound in this series where d~-p~ bonding was not possible.

~NHPh ~NHPh _

~NMe2 ~Me3 X

(XXXV) (XXXVI) - 23 -

Quaternisation of (XXXVJ to give (XXXVIJ would give a salt in which d'll:-p?C bonding could not possibly occur, since the 3d orbitals on nitrogen are at too hi0h an energy to permit any overlap with the o-phenylene '7C electrons. Hence, if d?C-p'll: bonding is responsible for the NH proton shifts in the phenarsazine methiodides, then no marked downfield shift of the NH proton should occur in the N.M.R. of (XXXVI). Dimethylphosphonate has recently been proposed as an efficient N-methylating agent for aryl amines, 29 and it was hoped to obtain (XXXV) from 2-aminodiphenylamine with this reagent as the diphenylamino group was expected to react only slowly. When the reaction was carried out however, the tris methylated product (XXXVII) was obtained exclusively.

( XX.XVII) When 2-aminodiphenylamine was reacted with an excess of methyl iodide and potassium carbonate in refluxing benzene for 28 hr. , ( XXXV) vrg,s obtained in 62% yield. Another route to this compound was also attempted. Secondary and tertiary amines have been recently obtained in good yield by the reaction of primary or secondary - 24 - aromatic amines with halobenzenes and sodamide in hexamethylphosphoramide (XXXVIII). 30

Thus triphenylamine was prepared in 65% yield from bromobenzene and aniline, while diphenylamine was obtained in 30% yield by varying the quantities of reactants. A benzyne-type intermediate was proposed for these reactions, the relatively high yields being due to the use of the very powerful dipolar aprotic solvent, (XXXVIII).30

i >PhNH- Na+> Ph2NH iDH2o

2-Chloro-N,N-dimethylaniline was reacted with sodamide and aniline in hexamethylphosphoramide and a 37% yield of an N',N'-dimethylaminodiphenylamine was obtained. However, this product had different physical properties to (XXXV;, obtained by the unequivocal route described above, and was hence the meta isomer, which could arise from the benzyne intermediate (XXXIX).

©(~e2 NaNH2 > q:NMe2_1 ~NMe2

HNPh HNPh (XXXIX) - 25 -

This isomer would be expected on steric grounds but not on electronic grounds. N-Methylation also proved a problem when (XXXVJ was reacted with methyl iodide to give the salt (XXXVI). A mixture was obtained and no salt could be isolated. The desired salt was obtained, however, when equimolar quantities of the amine and methyl p-toluenesulphonate were heated in the absence of solvent.

A para amino arsine (XL) and its methiodide (XLI) were also prepared in order to eliminate the possibility that the shift observed in the phenarsazine methiodides was simply an electrostatic effect of the proximity of the NH proton to the positive arsonium centre.

r

(XL) (XLI) In the para compound d~-p~ bonding of the type suggested by structure (V) is still possible, but electro­ static f~ctors should not be important. p-(AminophenylJdiphenylarsine (XLII) was prepared by the reaction of phenylmagnesium bromide with p-aminophenyl­ diiodoarsine hydriodide (XLIIIJ. - 26 -

(XLIII) (XLII) (XLII; was then reacted with sodamide and bromobenzene in hexamethylphosphoramide. A mixture of two arsines was obtained. The less polar arsine showed no NH absorption in the infrared and its methiodide showed a methyl:aromatic ratio in the N.M.R. spectrum of 3:24 and was hence the N,N-diphenyl product (XLIV).

Ph 2N-@-AsPhz

(XLIV) The other arsine was the desired product (XL). Difficulty was again experienced in obtaining the methiodide (XLI). When the arsine was refluxed with an excess of methyl iodide, a mixture of arsonium salts was obtained and the N.M.R. spectrum indicated a 2:1 mixture of N-methylated arsonium salt (XLV):unmethylated salt (XLI).

(XLV) - 27 -

By allowing the arsine to stand at room temperature for two weeks with 1.2 moles of methyl iodide in aceto­ nitrile, (XLI) was eventually obtained. - 28 -

1.3 N.M.R. Spectra

The NH proton positions in the 10-substituted phenarsazines studied and in their methiodides, were reported in Table 1 (see Introduction). The effect of

solvent on the NH proton position was determined for the 10-(o-chlorophenyl) compound (XII) and its methiodide (Table 2J.

TABLE 2 Effect of solvent on the NH proton signal position

(b) in 10-(o-chlorophenyl)-5,10-dihydrophenarsazine and its methiodide

' Solvent Compound CDC1 3 d6-DMSO Methanol

Arsine 6.21 9.33 8.40 Meth iodide 10.43 10.76 10. 23

There is a strong solvent effect in the arsine, more polar solvents shifting the NH proton signal downfield quite markedly. The effect of solvent on the NH position in the methiodide is significant, though small by comparison to the effect in the arsine. - 29 -

The spectra of all the arsines prepared were determined in CDC1 3 and unless otherwise noted, the methiodides were also determined in this solvent. Where the methiodides were not sufficiently soluble in CDC1 3, d6-DMSO was used. The spectra of the arsine oxides were determined in methanol, as these compounds were insoluble in both cnc13 and mso. Concentrations were kept very approximately equal in all cases and appeared to have a negligible effect on the spectra. The shift of the NH signal in the N.M.R. spectra of the phenarsazine methiodides relative to the position in the arsines was of the order of 4 ppm down.field. The NH signal position in the seven-membered ring heterocycle (XVII) was at b).91. In the methiodide of (XVII), the NH signal was hidden under the aromatic envelope when determined on the 60 M/cs instrument. Fre­ quency sweep decoupling experiments on a 100 M/cs instrument showed that the NH proton was coupled with the benzylic protons and that the NH-CH 2 grouping constituted an ABX pattern. Irradiation at the frequency of the NH signal caused the collapse of the CH 2 signal from an eight-line multiplet to a four-line multiplet. Irradiation of the benzyl signal caused the NH signal to collapse from an apparent triplet to a singlet. In this way the NH signal was established at b6.89. - 30 -

Thus the downfield shift of the NH proton on quaternisation of (XVII) was 2.98 ppm. This is considerably less than the 4.1-4.2 ppm shift observed in the phenarsazine methiodides. This would be expected if d'K-p 7~ bonding is responsible for the shifts in the methiodides since the possible conjugation pathway in the methiodide of (XVII) is considerably less than the pathway possible in the phenarsazine methiodides. The NH proton signal in the N.M.R. of the aminoethyl arsine (XXII) was at oJ.48 while the NH signal in 2-(N-phenylamino)ethylphenyldimethylarsonium iodide (XXXIV) was at 04.99; a downfield shift of 1.51 ppm. These two spectra are not strictly comparable since the parent arsine (XLVI) of (XXXIV) has an -A~~ePh grouping, whereas (XXII) has an -AsPh2 grouping.

Ph-NHCH 2CH 2-AsMePh (XLVI)

How·ever the effect of the extra phenyl group in (XX:IIJ would be expected to be comparitively slight. In the methiodides of these arsines no d'K-p'K bonding is possible since there is~ satur~ted centre between the nitrogen atom and the ~i~t~r~ary centre. The shift observed in these compounds couJd therefore be taken as a b'},se figure for t~~s whole series of compounds. The NH proton si6-nal ir. the aminoc-thyl phosphine

(Y.LVII) was at o 3 .83 and in the corresponding methiodide the position was 06.00; a downfield shift of 2.17 ppm.

PhNHCH 2CH 2PPh2

(XL VII)

The rm signal in 2-N 1 ,N 1 -dimethyl2.1I1inodiphenylamine

(XXXV) was at o 6.56. In the metho-p-toluenesulphonate of

(Y..XXVJ tr..e NH Rignal was hidden under the aromatic envelope which was in the region b 6. 55-7 .9. n2o exchange showed a one proton decrease i:r. the integral in the region between o 7.42-7.63 and hence the NH signal shift on quaternisation of (XXXV; was s, maximum of 01.07. This would also be expected if dTC-pTC bonding is responsible for the NH shifts in the phenarsazine methiodides since in the salt of (XXXV) the ~d orbitals on nitrogen are at too high an energy to

permit any overlap with the o-phenylene TC electrons. The sm9ll shift observed on quaternisation of (XXXVJ also provides evidence that the shift in the phenarsazine

methiodides is not due to electrostatic effects alone. If it were simply the proximity of the NH proton to the out1tern.~ry centre which caused the down.field shift of the NH proton jn the N.M.R. of the phenarsazine methiodides, then a simila~ shift would be expected in the methiodide

of (XXXV). The NH shift in p-( diphenylarsino) diphenylamine - 32 - methiodide ( XLI) .3lso indicated that electrostatic effects alone could not account for the downfield shifts observed in the phena.rsazine methiodides. The NH position in the

8rsir.e (XL) was b5.45. The position in the methiodide (XLIJ,

which was determined in d6-llv'IS0, was o 9 .00; a downfield shift of o 3. 55. This shift would be expected if d-r.-P?'i. bonding was occurring in the methiodide but not if electro­ static effects were responsible. The spectra of the oxide of the 10-(o-chlorophenylJ compound (XII; and the 10-methyl phena.rsazine were

determined in methanol. The NH signe.l was at b 10. 00 in the oxide of (XII) and at b10.11 in the oxide of the 10-methyl compound. The oxide of the 10-phenyl compound was too insoluble, even in methanol, for the N.M.R. spectrum to be determined. It is difficult to make meaningful comparisons using these spectra as the extent of solvent effects in the oxides could not be determined since they were insoluble in

DMS0 and cnc1 3 . However if the effect in the oxides is of

~ simil8r order to the solvent effect in the methiodides (see TGble 2), then the downfield shift of the NH proton in the oxides rel2ti ve to the position in the tertiary arsines is quite large and reflects the possible d?'i.-p?'i. bonding which could occur in these compounds. Finally it should be noted here that the NH signal

position in the 10-chloro compound (I) in CDc1 3 could not be Accurately determined. The signal was hidden under the - 33 - aromatic envelope between 06.80-8.00 and n2o exchange was not possible in this case because of the ready hydrolysis of (I). The NH signal is, however, further downfield than its position in 10-substituted phenarsazines (ca. 06.2), though only slightly compared to the shift in the phenars­ azine methiodides. This result indicates that, as has been suggested in earlier studies (see Introduction), some d -p ~ ~ bonding may occur in (I), the chloro group presumably being sufficiently electronegative to contract the d orbitals on arsenic to permit overlap.

- 34 -

1.4 Ultraviolet Spectra The ultraviolet spectra of a number of aryl arsines have been studied in some detail. 27 Figu.re 1 shows the ultraviolet spectra of triphenylarsine and its methiodide. There is a marked difference in the spectra and this difference has been ascribed to the presence of the lone pair on the arsenic atom in the case of the arsine and its absence in the arsonium compound. 31

The strong absorption band at 247 mµ in the arsine has been attributed to an n ➔ ~ * transition involving extensive conjugation between the lone pair on the arsenic atom and the phenyl groups, 32 and giving rise to an electronic change which may be represented by (XLVIII).33 Ph+s=g--, I'A 1-1\ .-__ ,,'I Ph

(XLVIII) The absence of the lone pair in the methiodide results in each phenyl group making an independent contribution to the spectrum, which consequently resembles benzene. The ultraviolet spectra of some nitre-substituted phenarsazines were recorded by Gibson and Johnson34 and rfohler and his co-workers15 also examined the ultraviolet

- ?5 - spectrum of (I). Apart from this early work, no other studies of the ultraviolet spectra of dihydrophenarsazines and their methiodides have been reported. The origin of the principal absorption bands in these compounds has not been determined. In the 10-substituted dihydrophenarsazines there is a lone pair present on both the arsenic atom and on the nitrogen atom and, by analogy with the type of interaction postulated in aryl amines and aryl arsines, 31 it might be expected that the interaction of both of these lone pairs with the phenyl rings would be responsible for the principal absorption bands in their spectra. In the phenarsazine methiodides the lone pair on arsenic is absent and, again by analogy with the spectra of arylarsonium methiodides, some diminution in the spectra of phenarsazine methiodides compared to the spectra of the phenarsazines themselves, at least in the intensity of the absorption bands, if not a considerable alteration in the spectra altogether, might be expected. Figure 2 shows the ultraviolet spectra of 10-(o-chlorophenylJ-5,10-dihydrophenarsazine (XII), its methiodide and oxide. In contrast to the marked difference in the spectra of triphenylarsine and its methiodide (Fi~re 1), the spectrum of the methiodide of (XIIJ is very similar to that of the arsine itself. There is a significant

- 36 -

increase in the extinction coefficient of the principal absorption band from 12,100 in the arsine to 15,500 in the methiodide. The arsine oxide shows similar behaviour. A similar pattern is aJ.so exhibited by 10-phenyl-5,10- dihydrophenarsazine, its methiodide 2nd oxide. The similarity in the spectra of the arsine and the rnethiodide would seem to indicate that some form of interaction between the arsenic atom and the phenyl rings is occurring in the methiodide, in a similar manner to the conjugation involving the arsenic lone pair in the arsine. Since the lone pair on arsenic is not present in the methiodide, then it seems likely that in the methiodides,

overlap of the nitrogen lone pair with the o-phenylene ~ electrons and the contracted 4d orbitals on arsenic, to give the type of d~-p~ bonding suggested to explain the N.M.R. spectra of the phenarsazine methiodides, is occurring. A similar argument can be applied in the case of the arsine oxide. 10-Methyl-5,10-dihydrophenarsazine and its methiodide show slightly different behaviour (Fieure 3), an extra band appearing to slightly longer wavelength in the methiodide. Essentially the same type of behaviour was observed in the spectra of 5-phenyl-10-rnethyl-5,10-dihydrophenarsazine and its methiodide, which were prepA.red in the course of the synthetic study reported in Section 2.

p-(Diphenylarsino)diphenylamine (IlJ and its methiodide also show ul tr~violet spectr3.l characteristics which suggest that d -p bonding is occurring in the 7C 'TC methiodide (Fir;ure 4). By analogy with the behaviour of triphenylarsine 211d its methiodide, the spectrum expected for the methiodide of (XLJ should essentially resemble diphenylamine ( which has "-max 284 mµ). Instead there is a

1 5 ffll.-l shift to longer wavelength of the absorption maximum, rel~tive to its position in the arsine, and a slight increase in the extinction coefficient. These features, combined with the overall similarity in the spectra,suggest that, in the methiodide, d~-p~ bonding, which can be represented by resonance structures such as (XLIX), is OCCll!'ring.

Ph _;==\_+ N-Ph -<->

(XLIX) ThP- spect~a of the seven-membered ring heterocycle (XVII) and its methi'.)dide also gave support to the d'it-p~ bonding nostulated in the methiodides of this series of compounds

(Figure 5). The shift of th~~ band at 320 mµ in the arsine te> :n1 mp in the rnethi0dide seems unaccountable unless sor.ie form of interaction involving the arsenic atom is occurring in the methiodide. 40 Figure 5

• 'I I and I I I oc.:)QJ Methiodicle ' I Ph '

' 'I I I 10 I I 'I I I ,,•,, Solt • ' I I \ I , \ ' Arsine '\ I,' I \ I I \ I I I \ ,... ,' ' \ \ \ ' '' \ \ \ \ \ \ \ I \ I I \ I \ I \ I I I '\ I \ I \ I \ I \ I I

l)Q 200 1.5 Mass Spectra There have been very few mass spectral studies of organoarsenic compounds reported in the literature. 36 Buu-~·foi et al. 37 examined the mass spectrg, of 10-chloro- 5, 10-dihydrophenarsazine (I) and 10-methyl-5,10-dihydro­ phenarsazine and assigned the principal peaks. In the course of this study and the synthetic study reported in Section 2, the mass spectra of a number of dihydrophenarsazines and related compounds were determined. The fragmentation patterns observed gave supporting evidence to the view that d~-p~ bonding can occur in the phenarsazine ring system. Table 3 shows the relative abundance of the parent ion, and of the most abundant and second most abundant ions, and t~eir assignments in a series of related compounds (L, LI, LIIJ investigated in this study.

(1) (LIJ (LII) - 41 -

The bonds to the arsenic atom are the weakest bonds ii the phenarsazine system (see Table 4) and it might be expected that fragments arising from rupture of these bondi would be prominent in the spectrum.

TABLE 4 Bond Energies (Kcal/mole)

Bond Bond Energy Ref.

C-C 80 38 C-N 66 38 N-H 92 38 As-C 60 39 As-I 49 40

In every substituted dihydrophenarsazine which was studied, the most abundant ion was species (LIII), where

I R WRS H, Ph or Me. +

(LIIIJ - 42 -

This assignment was confirmed by accurate mass matching in the case of (L, R = Me, R' = HJ and it is reasonable to assume that the assignment is correct in the other compounds studied. The appropriate metastable peak was observed in every phenarsazine studied for the fragmentation of the parent molecular ion to (LIII). It is difficult to see why the exocyclic bond should 8lways cleave preferentially, particularly when R = phenyl in (L), unless the resonance stabilisation of the species formed involves not only the o-phenylene ~ electrons, but also the nitrogen lone pair. The ion (LIII) could be stab­ ilised by contributing resonance structures such as (LIV;.

(LIV) As in the case of the phenarsazine methiodides where d -p bonding hns been postulated to account for the NH ~ 'JI". signRl position in the N.M.R. spectrum of these salts, the lone pair on nitrogen is contributing to the stabilisation of the positive charge on arsenic in structure (LIV;. It is not necessary to invoke the involvement of the d orbitals on arsenic in this case, though with the co~traction of the - 43 - d orbitqls by the positive charge, involvement of the arsenic d orbitals in resonance structures such as (LIV) is a possibility. The second most abundant ion in the phenarsazines studied was, in most cases, the carbazole species (LV) resulting from extrusion of the arsenic atom in (LIII).

+•

(LV) (R' = H, Ph or Me; This assig~ment was also confirmed by accurate mass matching in the case of (L, R = Me, R' = HJ and the appro­ priate metastable peak was observed in all the phenarsazines studied for the fragmentation of (LIII; to (LVJ. With the similarity in results obtained in such a vaxiety of compounds of the dihydrophenarsazine series, it is possible to draw up a general fragmentation pattern for the phenarsazine series (Figure 6). In view of the fragmentation pattern observed in the phenarsazines it seems reasonable to localise the charge in the molecular ion on the arsenic atom. +• R' >©Qg) t,~ ~ R 1 R' R' )OC:© + R• q~< + ~ R'

a~As •• l R'

+ As

Figure 6 - 45 -

The view that the ion (LIIIJ which arises in the phenarsazine mass spectra is particularly stable received support from the mass spectrum of the seven-membered ring heterocycle (XVIIJ. Here the phenarsazine ring system is not present and the ion resulting from fission of the exocycJic As-Ph bond (LVIJ was of only 5~~ relative abundance. +

(LVI) It should be noted here that the mass spectrum of (I) reported by Buu-Hoi et a1. 37 showed a very weak parent ion (0.2% relative abundance) and the most abundant ion was m/e 241, which they attributed to the phenarsazine ion (LVII) obtained by loss of HCl from the parent ion.

+

(LVIIJ In contrast to their result, the mass spectrum of (I) obtained in our study showed a different order of peak intensities Rltogether (Table 5). - 46 -

TABLE 5 Mass Spectrum of (I) at 70 eV

! Buu-Hoi et al. This Study m/e Relative Abundance Relative Abundance ( %) ( %) , 7 -0.2 64 { c1 279 35c1 2 277 ,,.,,o. 1 2 243 -

I 100 40 I 242 ! 100 24 I 241 2 214 3.5 15 36 I 167 20 166 31.5 3 151 6 4 140 6.7 4 139 6.5 129 1 - 1 120. 5 4-5

study was of 48% The parent ion observed in this 35c1), while m/e 241 relative abundance (m/e 277 using Metastable peaks were was of only 20% relative abundance. 212 and m/e 115. These observed in the spectrum at m/e m/e 277 --+m/e 242 and correspond to the transitions - 47 - m;e 242 ~ m/e 167, respectively. A low energy (11 eVJ spectrum of (I; gave the peaks indicated in T~ble 6.

TABLE 6 11 eV M~ss Spectrum of (I)

m/e Rel8tive Abundg,nce (~)'I·

279 34 278 16 277 100 243 2

242 18 241 18 167 2

Buu-Hoi et al. cornnented on the ease of rupture of the As-Cl bond on electron impact; the low energy spectrum observeo by U:'l would not seem to support this conclusion. Instrument differences are known to cause marked variati~ns in spectra in somP. cases and could account for thP. vg_riqt;_on in the mass spectra o~ (I). 4·1 :Buu-Hoi et al.

determined their ~"Jpectre1 on qn Atlas CE4 instrument at

1 0 e 'I ~.nd qt ."n unspecified probe temper':',tu.re. The spectra - 48 - in this study were determined on qn AEI ~S9 instrument, and in tl-ie case of (IJ the probe temperature was 200°. The peak intensities in the mass spectrum of 10-methyl-5, 10- dihydrophenarsazine reported by Buu-Hoi et al. were in good agreement with those observed for that compound in this study. It is of interest that even in the phenarsazine oxides which were studied, the most abundant ion was species (LIII). This is in contrast to the phenophosphazine compounds studied. Here the most abundant ion was (LVIII) and this result would seem to indicate that the As=O bond is much weaker than the

P=O bond (128 Kcal/mole in Ph3Po), 42 though no thermo­ chemical data on the strength of the As=O bond are available. +

(LVIIIJ - 4q -

1.6 Experi~ental General: Mel ting ...Q.Q_ints were determined on a Kofler hot stage apparatus Rnd are uncorrected. Unless otherwise stated all compounds are colourless. Infra-red SRectra were recorded on a Perkin-Elmer 137 Infracord or a Hilger and Watts Infrascan instrument. Ultra-violet spectra were recorded on a Perkin-Elmer 1.~7 UV model instrument. 95% Ethanol was used as solvent in all cases.

Nuclear Magnetic Resonance spectra ( N.M.R.) were recorded on a Varian A60 N.M.R. instrument or a Varian HA100 N.M.R. instrument. Peak positions were recorded as parts per million (b) downfield from tetramethylsilane and are accurate to =0.01 ppm. The position of multiplets is recorded as the central point of the integral. Singlets are abbreviated, s., end multiplets, mult. Mass spectra were determined on an AEI MS9 double focussing instrument. Relative abundance measurements are accurate to ~5%- Gas-liquid chromatography (g.l.c.J was carried out on a Perkin-Elmer model 800 using a 6 ft. x fin. column rrncked with SE]0 (5f) on Chromosorb G, usine a flame ionisation detector. - 50 -

So_l_'{_ents were distilled before use. T.b,y and Baker br8.nd "Anhydrous Jther" was used where anhydrous ether was required. Tetrahydrofuran (T.H.F.; was refluxed over lithium aluminium hydride and distilled immediately before use. Light petroleum refers to the fraction b.p. 60-80°. Anhydrous sodium sulphate was used for drying organic solutions and evaporations of solvents were carried out in vacuo. All reactio~s involving aryl or alkyl lithium reagents were carried out under dry, oxygen free nitrogen. Aryl and alkyl lithium reagents were titrated by the double titration method of Gilman and Cartledge43 using 1,2-dibromoethane. Peter Spence (Grade HJ alumina or BDH silica gel was used for column chromatography. Preparative thin layer chromatoGraphy (T.L.C.; was carried out on 9" x 9" plates which were coated with a slurry of Merck silica gel Hor

HF254 (30 g) in water (65 ml). Microanalyses were performed by Dr. E. Challen of this department or by the Australian Microanalytical Service, Melbourne. - 51 -

Section 1. Exnerimental Index Page 1. Known Compounds 52

2. 10-(o-Chlo~ophenylJ-5,10-dihydrophenarsazine 53 (XII) and its methiodide 3. 10-0xo-10-(o-chlorophenylJ-5,10-dihyd.rophenars- 55 azine (XIV) 4. N-(o-Bromobenzyl)-o-bromoaniline (XVI) 56 5. Lithiation of N-(o-bromobenzylJ-o-bromoaniline - 56 carboxylation experiments 6. 5-Phenyl-10,11-dihydrodibenz(b.fJ[1,4]­ 58 azarsepine (XVII) and its methiodide

7. Isolation of 1,2-diphenyl-2,1-benzazarsoline (XXI) 60 8. 2-(N-Phenylamino)ethyldiphenylphosphine and 61 its methiodide 9. 2-(N-Phenylamino)ethyldiphenylarsine (XXII) 62 and attempted methiodide preparations 10. N-(o-Bromobenzyl)aniline (XXVI) 64 11. N-(o-Diphenylarsinobenzyl)aniline (XXVJ 66 12. (o-Bromobenzyl)diphenylmethylarsonium bromide 68 (XXXII)

13. N-(2-Iodoethyl)aniline hydriodide 68

14. 2-(N-Phenylamino)ethyldimethylphenylarsonium 69 iodide (XXXIV) 15. 2-(N',N'-Dimethylamino)diphenylamine (XXXV), 71 acetamide and metho-p-toluenesulphonate

16. (p-Aminophenyl)diphenylarsine (XLII) and 73 acetamide. 17. (p-Diphenylarsino)diphenylamine (XL) and its 74 methiodide. - 52 -

Known Compounds

10-Chloro-5,10-dihydrophenarsazine (I) was prepared from arsenic trichloride and diphenylamine by the method of

Burton and Gibson. 3 m.p. (CC1 4 ) 192°. lit. 3 193°.

10-Substituted-5,10-dihydrophenarsazines were prepared by the reaction of excess Grignard reagent with (I) accord­ ing to the method of Aeschlimann. 6 10-Phenyl. m.p. 148°. lit. 6 m.p. 148-9°. Methiodide. m.p. 150-152°. decomp. lit. 6 m.p. 158°. Oxide. m.p. 365-370°. decomp. lit. 16 m.p. 280-300°. decomp. 10-Methyl. m.p. 104°. lit. 6 m.p. 105°. Methiodide. m.p. 263-265°. decomp. lit. 6 m.p. 268°. Oxide. m.p. 199°. lit. 16 m.p. 239.0

Phenyldichloroarsine was prepared in 60% yield by the reduction of phenylarsonic acid with sulphur dioxide and hydrochloric acid and a trace of iodine. b.p. 2 88-90°. lit. 21 250-255 0 .

Diphenylchloroarsine was prepared by the reaction of phenyldichloroarsine with triphenylarsine at 300° for 4 hr. b.p.0 .~ 110-115°. lit.44 b.p. 15 185°. - 53 -

Phenyldimethyla.rsine was prepared by the reaction of phenyldichloroarsine with an excess of methylmagnesium 21 iodide. b.p. 30 118-122°. lit. b.p. 14 85°.

Diphen.ylmethylarsine was obtained in an analogous manner by the action of methylmagnesium iodide on diphenyl- o 21 6 o chloroarsine. b.p.0 _7 114-122. lit. b.p. 15 1 3-170.

o-Bromobenzyl bromide was obtained by the bromination of o-bromotoluene according to the method of Shoesmith and 45 84 860 . 45 o Slater. b.p. 1 - . lit. b.p. 12_16 120-140.

2-Bromoethylaniline hydrobromide was prepared by the action of hydrobromic acid on N-phenylethanolamine. m.p. 135°. lit. 46 137-138°.

N-Phenylaziridine was obtained in 53% yield by the action of sodium hydroxide on 2-bromoethylaniline hydro­ bromide according to the method of Heine et ai. 47 b.p. 8 70-72°. lit.47 b.p. 13 70-70.5°.

10-(o-Chlorophenyl;-5,10-dihydrophenarsazine (XII) 10-Chloro-5,10-dihydrophenarsazine (30 g) was added in small portions to a solution of o-chlorophenylmagnesium bromiae48 (47.5 g, 2 mole) in anhydrous ether (90 ml). After - 54 -

completion of the addition the mixture was refluxed for 15 min. The mixture was cooled and hydrolysed with aqueous ammonium chloride solution and the ether layer was decanted and dried. Evaporation of the solvent gave a viscous oil which crystallised on prolonged scratching. The product was recrystallised from ethanol (29 g, 76%) m.p. 110°. It was difficult to obtain good analytical figures for this compound. The mass spectrum showed peaks at 397 and ?-99, each of relative abundance 1. 5%, indicating the presence of some 10-(o-bromophenylJ-5,10-dihydrophenarsazine. The parent ion for the 10-(o-chlorophenyl) compound was at 353 and of relative abundance 42~;. The best analytical figures obtained were: Found: C, 60. 4%; H, 3. 6%; N, 4-2% Cale. for C18 H13 AsNCl: c, 61 . 1%; H, 3 • 7c1-,o, N, 4.0% b(CDC1 3) 6.97 (12H, mult., ArH); 6.21 (1H, s., NH, exchanged with D20 J. }..max (E.J 216 (35,400), 284 (12,100), 311 (shoulder; (8,100), 330 (7,?00).

10-Methyl-10-(o-chlorophenylJ-5,10-dihydrophenazarsonium iodid The arsine (1 g) was refluxed with methyl iodide (2 mlJ

in benzene (2 ruJ for 3 hr. The brown ~ITT nhich separated was recrystn.llised from □ eth8-'11ol-ether ( 1 g, 71fJ m.p. 136°. - 55 -

Found: C , 4 5 • 2~'; 3 , 3 • 6%; N, 3 • 1% •

Cale. for c19H16HAsClI: C, 46.0f; H, J.2%; N, 2.8%. b(CD~l 3 ) 10.43 (1H, s., NH, exchanged r,ith D20); 7.52 (12H, nul t. , ArH); 2.

>-..m (t) 219 (48,900), 275 (15,500), 331 (10,100) . . 8.X

1 0-0xo-10-( o-chloronhenyl )-5, 10-dih,yr'lrophenarsazine ( XIV)

The oxi-l~ ":r ~ :r:rep8re a -:iccording to the generol method

~f Razuvrev and Malinovski 16 as follows. A solution of the rirsine (0.5 ~) in ethanol (15 ml) was diluted with water until the soJu~ion was cloudy. The solu~ion was titrated with alcoholic iodine solution (0.1M) until a bright yellow colour persisted in the solution. Water was added period­ ically durir:.; the ti tr at ion such that the total volume at the end point was ~- 80 ml. The solution vms neutralised

':ri th aqueous sodium hydroxide ( 0. 1M) using phenolphthalein ind i C8tor. The re suJ. tine precipitate was filtered and dried ot 150°/0.2 mm for 1 hr. The product was recrystallised from aqueous methanol ( 0. 3 g, 58%; m. p. 294-298° ( de comp.) • Tbe oxide v,as insoluble in chloroform and only sparingly 801uble in dirrethyl sulfhoxide.

") 501 Found: C, 58.1;:; H, - : • I('

Cnlc. for c18H13 NAs0Cl: C, 58.5~; H, J.51; N, ~-8%. b(!,!e0H) 10.J0 (1H, bro-::1d s., !'TE); 8.3: (1H, mult., ArH);

,.., • 4 1 ( 11H, mul t. , ArF) .

(l) 218 ( 10 ,200), 275 (16,200;, 320 (::',400), 345 - 56 -

(shoulder) 7,600.

l': -( o-Bromobenz.yl J-o-bromoanilir.e (XVI) Anhydrous potassiun carbonate (12.6 g), o-bronobenzyl bromide ( 2_:>, .4 g) 8nd o-bromooniline ( 16.1 g) in isoamyl ,:ilcohol (50 mlJ containing a trace of copper powder, were refluxed for 16 hr. The mixture was cooled ond the isoamyl ~lcohol was removed by steam distillation. The residue was extr~cted with chloroform and the extract was washed with vrater and dried. Evaporation of the solvent gave a crystal­ line mass which was recrystallised from ethanol ( 18 g, 6776) rn.. p. 67 0.

Found: C, 45-7%; H, 3-4%; N, 3.8%. Cale. for c13H11 NBr 2: C, 45.8%; H, 3.2%; N, 4.1%. b(CDC1 3) 7.19 (8H, rrrult., ArH); 4.85 (1H, broads., NH); 4.43 (2H, doublet J 5.5 Hz, CH 2).

Lithiation of N-(o-bromobenzyl)-o-bromoaniline

A. With 2.7 mole of n butyl litr~ium-diamine complex n Butyl lithium in petrol (4.7 ml, 1.7M, 2.7 mole) vras added to a solution of N-(o-bromobenzyl)-o-bromoaniline (1 g) in ether (10 ml) containing N,N,N 1 ,N 1 -tetramethylethylene­ di3mine (0.91 g, 2.7 mole). The solution ITas stirred for 15 min. n.nd poured onto solid carbon dioxide. '.'later ( 20 ml) ~~s added ~nd the solution was extracted with ether. The - 57 - ethereal extract was extracted with sodium bicarbonate solution and the bicarbonate extract was acidified and extracted with ether. The ethereal extract was dried and evaporated to ,'.::ive 0.42 g (53%) of crystalline acid, m.p. (eth2.nol) 151°. Found: C,55.0%; H,4.2%; N,4.6% Eq.wt. 28C

Cale. for c14H12NBr0 2: C,54.95%; H,3-9%; N,4.6% Eq.wt. 28E A sample was esterified with ethereal diazomethane solution for the N.M.R. study, m.p. (ethanol) 71°. b(CDC1 3) 7.37 (8H, rrru.lt., ArHJ; 4.97 (1H, s., NH); 4.75 ( 2H, s. , CH 2 ) ; 3 • 90 ( 3H, s. , COOMe) .

B. With 5.8 mole of n butyl lithium-diamine complex n Butyl lithium in petrol (10 ml, 1.7M, 5.8 mole) was added to a solution of N-(o-bromobenzyl)-o-bromoaniline (1 g) in ether (10 ml) containing N,N,N',N'-tetramethylethylene­ diamine (1.95 g, 5.8 mole). The solution was stirred for 30 min. and poured onto solid carbon dioxide. Water (20 ml) was added and the acidic fraction isolated as before, to give 0.69 g (87%) of the diacid, m.p. (ethanol) 208°.

Equiv. wt. 147- Cale. for c15H13 No 4 135.5. A sample was e sterified with ethereal diazomethane solution, m.p. (ethanol) 104°. Found: C, 68.2%; H, 5.8%; N, 4.8%

Cale. for c17H17 No 4: C, 68.25%; H, 5-7%; N, 4.7%• - 58 - b(CDC1 3J 7.39 (9H, mult., ArH and NH); 4.83 (2H, s., CH 2); J. 89 ( 3H, s. , COOMe) ; 3. 8 3 ( 3H, s. , COOMe) .

Methyl H-( o-bromo benzyl) anthranilate ( XIX) Anhydrous potassium carbonate (1.77 g), methyl anthrani­ late (1.93 g) and o-bromobenzyl bromide (3.2 g) in isoamyl alcohol (10 ml) were warmed at 80° for 7 hr. The mixture was cooled and filtered and the residue was washed with chloroform. The filtrate and chloroform washings were combined and evaporated and the isoamyl alcohol was removed by steam distillation. The residue was recrystallised from ethanol (2.6 g, 64%) m.p. 130°. Found: C, 56.5%; H, 4.45%; N, 4-3% Cale. for c15H14NBr0 2: C, 56.3%; H, 4-4%; N, 4.4%­ b(CDC13) 8.24 (1H, s., NH); 7.30 (8H, mult., ArH); 4.52 (2H, doublet J 6 Hz, CH 2); 3.86 (3H, s., COOMe).

5-Phenyl-10,11-dihydrodibenz(b,f)[1,4]azarsepine (XVII) N-(o-Bromobenzyl)-o-bromoaniline (7 g) in anhydrous ether (100 ml) was added dropwise to a solution of n butyl lithium in petrol (70 ml, 1.7M, 5.8 mole) containing N,N,N',N'­ tetramethylethylenediamine (14.4 g, 5.8 mole). The mixture was stirred for 30 min. and phenyldichloroarsine (12.5 g) in ether (40 ml) was added dropwise. The mixture was stirred for 1 hr and hydrolysed with water (150 ml). A large amount - 5g - of the precipitate formed during the dichloroarsine addition did not dissolve on hydrolysis. The organic layer was decanted, washed with water and dried. Evaporation of the solvent gave a brown oil (12 g). Trituration with ether precipitated a small amount (0.8 g) of phenylarsenoxide, identified by comparison with an authentic sample. 21 The oil was vacuum distilled and three fractions were collected. 1. b-P·o.3 68-80° (2.3 g). 2. b-P·o.3 80-120° (0.9 g).

3. b.p.0 _3 180-210° (3.1 g). Fraction 1 was (by t.l.c.J the least pola.r product. N.M.R. of this fraction showed a high aliphatic:aromatic ratio (6.9:1) This fraction was not further investigated. Fraction 3 was (t.l.c. in 1:9 chloroform-benzene) a mixture of three products. These included some material of similar R.F. to fraction 1, a product of R.F. 0.6 and some baseline material Chromatography on alumina (100 g) using petrol-benzene (7:3) as eluent gave 0.4 g (4.5%) of the desired heterocycle which had an R.F. of 0.6 (t.l.c. in 1:9 chloroform-benzene). The compound was recrystallised from ethanol, m.p. 117°. l,!nss spectral analysis - Found: Parent 333.0492

Cale. for c10H16NAs: Parent 333.0498. b(CDC1 3) 7.27 (13H, mult., ArH); 4.27 (2H, s., CH 2); 3.91 ( 1H, s. , NH) .

}-.m~x(t) 221 (28,000), 240 (shoulder; (16,400), 320 (3,300). - 60 -

5-Phenyl-10,11-dihydrodibenz(b.f)[4,1]azarsepine methiodide The arsine (45 mg) and methyl iodide (1 ml) were refluxed

in benzene (2 mlJ for 1 hr, the solvent was removed and the residue was recrystallised from methanol-ether (28 mg, 45%) m.p. 132 0 • b (cnc1 3) ( 100 M/c with frequency sweep decoupling) 7.60 ( 13H, mult., ArH); 6.89 (1H, triplet J 6Hz, NH); 4.59 (2H, 8 line

mult., JAB 16.5 Hz, JAX 6.5 Hz, JBX 5Hz, CH 2); 2.80 (3H, s., CH 3). "'max(£) 223 (1.5,400), 260 (7,100), 330 (3,100).

Acid treatment of ether insolubles in heterocycle preparation Isolation of 1,2-diphenyl-2,1-benzazarsoline (XXI) The ether insoluble gum which separated during the heterocycle preparation was refluxed in a mixture of ethanol ( 50 ml) and hydrochloric acid ( 50 ml, 10MJ for 4 hr. Evapor­ ation of the solvent and digestion of the residue with chloroform-ethanol (1:1) left 1 g of insoluble crystalline material shown to be N,N,N',N'-tetramethylethylenediamine bishydrochloride by comparison with an authentic sample. The ethanol-chloroform solution was evaporated and the residue dissolved in benzene. Some benzene insoluble material was discarded. The benzene solubles (1.3 g) were chromatographed on alumina (50 g) using petrol-benzene (1:1) as eluent. The first product eluted (0.26 g) was recrystallised from ethanol - 61 -

333 Found: C, 68.1%; H,4-7;~; E,4.0% Parent N,4.2% Parent 333 c~_lc. for c10H16NAs: C, 68.5%; H,4.8f; ArH); 4-93 (2H, AB quartet J 14.8 Hz b(CDC1 5 ; 7.28 (14H, mult.,

CH 2 J. a Further elution of the material on the column gave mixture comprising at least 7 spots (t.l.c.J.

2-(N-Phenylrunino)ethyldiphenylphosphine (XLVII) g) was A solution of lithium diphenylphosphide (6.45

prepared by stirring a solution of diphenylchlorophosphine g) for 5 hr. (7.4 g) in dry T.H.F. (30 ml) with lithium (0.47 added dropwise N-Phenylaziridine ( 4 6; in dry ether ( 75 ml) v,as was cooled over 1 hr. The mixture was refluxed for 1.5 hr, ether layer C1nd hydrolysed ,.-,i th air-free water ( 30 ml). The atmosphere and dried. Evaporatior 1::1.:=i dec:=rnted under a nitrogen distillec of the sol vent gave a colourless oil which rms vacuum phosphine slowly b.p. 0 _6 202-206° (7.3 g, 71%). The m.p. 42°. crystR.llised 8-'Yl.d was recrystallised from methanol, Found: C, 78.6~; H, 6.5~; N, 4.45% N, 4.6%. Cale. for c20H20NP: C, 78.7f; H, 6.6%; s.' NH); j. 25 ( 2H' b ( ~n0.1.,) 7.:: ( 1 ~-:~' 111.ll t. ' ArH); 3. g l ( 1H' .J

ide .'2-( N-:_P_h_e_I1Y_l_c015F:.o)_e_"t~l dirhenylmetJ!.Y_:lpho sphoni l!l!. _t._o_d were The pho3phine (0.65 g; and me+,i1yl iodije (0.32 gJ

✓ oil ·Nhich '"·efluxed in ben,"..e"l:.~ ( '.? ml .1 for 2 hr. Tha yellO\' - 62 -

:Jeprirated could not be crystallieed 2.nd the N.i'.1.R. s-pectrum

·.,'.18 run o!'l the crude oil. o(COC1 1 1 7.56 (15H, mult., ArH); 6.00 (1H, s., NH, exchanged ':1ith D2o); l.66 (4H, mult., CH 2CH 2 ); 2.80 (3H, doublet J 14 Hz, CH 3 J. The crude oil ·aas dtssolved in methanol and treated with n..queous sodi'..tm tetraphenylborate solution. A white gum separ~ted which could not be crystallised. Standing of the solvent-free gum for one month induced crystallisation. The snlt was recrysttllised from aqueous methanol, m.p. 123°. ,., Found: v, 84. 1%; H, 6 • 7d•;o, N, 2.4%

Cale. for c45H43 NPB: c, 84.5%; H, 6 . 7,', .: '• N, 2.2%.

2-(N-Phenylamino)ethyldiphenylarsine (XXII) A solution of lithium diphenylarsenide was prepared according to the method of Aguiar 8..Ild Archibald49 as follows.

TriphenylA.rsine (7.68 g) in dry T.H.F. (30 ml) was stirred under nitrogen with lithium (0.35 g) for 5.5 hr. tert-Butyl chloride ( 2. )2 0 ; in dry ether ( 5 ml) was added to destroy the phenyl lithium formed. N-Phenylaziridine (3 g) in dry ether (50 mlJ was added dropwise over 0.5 hr and the solution

\.'3.S refluxed for 1. 5 hr. The mixture was cooled and hydrolysec with water ( 1,0 ml) and the ether layer was decanted and dried . ..:vaporation of the solvent gave an oil which was vacuum nistilled, b.p.1 200-206°. 6.8 g. - 61 -

T.l.c. showed the presence of a snall amount of triphenylarsine ( presumably carried throuGh from the arsenide preparation), together with the desired product. This was removed by chromatography on alumina using petrol-benzene (7:3J as eluent. The triphenylarsine was eluted first and comprised 15% of the crude product. The aminoethyl arsine ( 5. 8 g, 66~1-) was a colourless oil. Found: c, 69. 2%; H, 6. 1%; N, 4-1% Cale. for c20H20NAs: c, 68.8%; H, 5-7%; N, 4.0%. b ( CDCl 3) 7.28 (15H, mul t., ArH); J.48 (1H, s.' NH, exchanged

Attempted £reparation of 2-(N-phenylamino)ethyldi£henyl­ methylarsonium iodide (XXIII)

The arsine (O.16 g) was refluxed with a slight excess of methyl iodide in benzene (4 ml) for 19 hr. The brown oil which separated could not be recrystallised. N.:M.R. ( cnc1 3) of the crude oil showed the presence of four singlets in the region 02.5-J.2. Warming equimolar amounts of the arsine and methyl p-toluenesulphonate, either neat or in benzene, gave

2 mixture of salts (by t.l.c.).

N-(2-Diphenylarsinoethyl)-N-phenyl-p-toluenesulphonamide p-Toluenesulphonyl chloride (2 g) was added to a solution of the ar3ine (1 gJ in anhydrous pyridine (6 ml) and the - 64 - mixture was warmed qt 80° for 0.5 hr. The mixture was cooled and poured onto ice. The resulting crystalline mass was filtered and recrystallised from aqueous ethanol (1 g, 69%), m.p. 227°.

~(CDC1 3J 7.46 (19H, mult., ArH); 3.93 (2H, mult., CH 2N); 2. 79 ( 2H, mul t., CH 2As) ; 2. 3 6 ( 3H, s. , CH 3) .

Attempted prepar2tion of 2-(N-phenylamino)et~ldiphenyl­ methylarsonium iodide via sulphonamide A solution of the sulphonamide (0.5 g) in chloroform (2 ml) was refluxed with methyl iodide (2 ml) for 20 hr. The solvent was evaporated and the residue was boiled with 80% sulphuric acid (5 ml) for 10 min. The black solution was cooled and made alkaline with aqueous sodium hydroxide solution. The solution was extracted with chloroform and the chloroform extract was washed with water, dried and evaporated to give 0.13 g of a darkly coloured oil. T.l.c. in methanol-chloroform ( 1: 19J showed at least three spots .. n-( o-Bromobenzyl) aniline ( XXVI) o-Bromobenzyl bromide (21.2 g), aniline (7.9 g) and ~nhydrous potassium carbonate (11.7 g) in isoamyl alcohol (50 ml) were refluxed for 4 hr. The mixture was cooled and fi1 tered and the residue was washed with chloroform. The - 65 -

filtrate and chloroform ,.,ashings were combined and evaporated a,nd the isoamyl alcohol was removed by steam distillation. The residual oil w2,,s dissolved in hot ethanol. On cooling

1.4 g of white crystals (Fraction A) separated. The mother liquors were evaporated and vacuum distilled. 0 1 • b.p.0 _2 120-140, 1.5 g. 2. b.p.0 _2 140-144°, 7.2 g ( Fraction B).

Frnction A. rn.p. 135°. The infrared spectrum showed no NH absorption and A was hence the bis-benzylated compound ( 1.4 g, 8%,). &(CDC1 3) 7.20 (13H, mult., ArH); 4.67 (4H, s., CH 2). Found: : C, 55.6%; H, 4-3%; N, 3.2% Cale. for C2J-I 17NBr 2: C, 55-7%; H, 3-9%; N, 3-2%. Fraction B crystallised slowly on cooling. m.p. 42-44° ( 7. 2 g, 3 3%) •

G(CDC1 3) 7.11 (9H, rnult., ArH); 4-35 (2H, s., CH 2); 4.23 ( 1H, s., NH, exchanged with D20). The compound darkened quite rapidly on exposure to air and. it was difficult to obtain good analytical figures. The compound was hence converted to its benzamide by the Schotten­ Baumann technique. m.p. (ethanol) 98°.

Found: C, 65-3%; H, 4.5%; N, J.9% Cale. for C20H16NOBr: C, 65.6%; H, 4.4%; N, 3.8%. - 66 -

Attempted preparation of N-(o-diphenylarsinobenzyl)aniline (XXV) via lithium diphenylarsenide on N-(o-bromobenzyl)anili

N-(o-Bromobenzyl)aniline (2.5 g) in dry T.H.F. (20 ml) was added dropwise to a solution of lithium diphenylarsenide

(4.4 g) in T.H.F. (20 ml). The solution was refluxed for 1 hr, was cooled, hydrolysed with water and extracted with ether. The ethereal extract was dried and the solvent removed, to give 6.4 g of a brown oil which was chromato­ graphed on alumina (240 g) using benzene-petrol (1:9) as solvent. Fraction 1. 0.51 g Triphenylarsine (t.l.c.). The eluent was changed to benzene-petrol (3:7). Fraction 2. 0.56 g Triphenylarsine and a more polar product The eluent was changed to benzene. Fraction 3. 1.05 g. m.p. (ethanol) 37°. lit. 50 m.p. for benzylaniline 37°. Mixed m.p., infrared spectrum and N.M.R. spectrum were identical with benzylaniline. Further elution of the column gave a mixture of polar products.

Preparation of N-( o-diphenylar sinobenzyl) ani_line vi a diphenylchloroarsine on N-(o-lithiobenzJ:l)aniline

N-(o-BromobenzylJaniline (2.5 g) in dry ether (40 ml) wo.8 added dropwi se to a solution of n butyl lithium in petro

('.?\.4 ml, 1.6M, 4 mole) containing N,N,N',T'T'-tetramethyl- - 67 -

ethylenediamine (4.4 g;. The solution was stirred for 1 hr,

dirhenylchloroarsine (7.5 gJ in ether (20 ml) added dropwise,

and the mixture was stirred for a further 1 hr. The mixture

w::i.s hydrolysed with water and the ether layer decanted and

dried. Evaporation of the solvent gave a brown oil (8.2 g) which was vacuum distilled.

0 Fraction 1. b.p.0 _3 120-150 , 1.02 g. Fraction 2. b • p • O • 3 190-220 o , 5 • 1 g. The N.M.R. spectrum (CDC1 3) of fraction 1 showed a high 2.liphatic: aromatic ratio ( 1: 3 .4). Fraction 1 was not further investigated.

Fraction 2 was (t.l.c.) a mixture of three products and was chromatoGraphed on alumina (170 g) usinG benzene-petrol (1:9)

3.S eluent.

Fr·1ction A. 0.47 g. T.l.c. identical with fraction 1 fro: the v~cuum distillation. Fraction B. 0.2 g was a mixture of fr'1ction A and a more polar product. The eluent wc"s ch~need to benzene. Fr~ction C. 1.1 g. Further elution

_---;~,ve polar products. Fraction C was a crystalline solid. r:1.p. (ethanol) 135° ( 1.1 g, 285'). b ( COC 1 J J 7 • 2 9 ( 19 II , r:u 1 t . , Ar H ) ; 4 . 4 2 ( 2H , s • , CH 2 ) ; 3 . 6 7 ( 1H, s., NH, ezch:1r1ced rlith D2o;. ::3.s~ spec trr'..l ~119.lysi s.

Fo'-.md: Parent 411 .0~)78

c~ le. for C IT ~TA • '.?5 "22·· 3 • Pnrent 411.0~68 ':'r2--i.tment of tf:i.s '.lrsi~e with either methyl iodide or methyl - 68 -

::i-toluenesulphon1te produced a mixture of r-:r sonium salts (t.l.c.J.

( o-Bromobenz.yl) di -phe n,ylmet qyla.rso nium bromide (X,UII)

Diphenyl~et'rylar sine ( 2. 7 g) was refluxed with o-bromo­

benzyl bro:n.ide (2.9 i) in benzene (2 ml) for 3 hr. The

nixture •:,as cooled and tri turated with ether and the crystql-

1 i ne mas8 'VB~ 4:il tered. The stl t wo_s re crystallj sea from n ~- t h '.1 no 1 - c t ho. r r ., ., c , 61 %) , m •r . 1 5 4° . Found: C, 48.25;:c; H, C, 48.6%; H, ~(CDG1 ) 7.61 (14H, 5 mnJt., ArHJ; 5.17 (2H, s., CH 2); 2.81 (:'.H, s., CH 3J. r.:rrolysis of ~!ie solt 2.t 2. bath temperature of 200° gave a colourless oil b.p. 0 _6 100-110°, which slovrl_y crystallised ~nd was identical to the starting salt.

N-(2-Iodoethyl)eniline hydriodide

N-PhenylethMola.mine ( 40 g) was added clropwi se to hydriodic :,cicl ( 114 ml, 55~{) at o0 • The mixture was fraction­

:0lly distilled until 65 ml of distillfde was collected. The residu'Jl liquid vms cooled and the resultir.;; cry3tPlline mass ,..,.,s filtered .'lnd washed repeotedly with et:1er. m.:r. (etl:.'.lnol­ c~~her) 112° (60 g, 55~'). - 69 -

Found : C, 2 5 .8 %; H , 2 • 9 ;~ N, 4 . 1 ;: .

2-( N-Phenyl ci.r:1ino) ethyl dimeth.yl phenyl arsoniurn. iodide ( XXXIV) 2-Iodoethylaniline hydriodide (1.5 g) and phenyldimethyl­ arsine (0,7 g) in eth2.nol (2 ml) were refluxed for 4 da.ys.

Tb c solution w:J.s tri tur8.ted vii th ether, the etr:er layer was decanted, and the residual .;;run was dissolved in chloroform.

The chloroform solution was washed in turn vrith water (x 3), 10f sodium carbonate solution (x 1), and water (x 1). The chloroform extr2,ct was dried and the sol vent removed. The residual gum was recrystallised from chloroform-ethyl acetate. m.p. 158° (0.21 g, 13~).

Found: C, 44.7%; H, 4.8%.

Cale. for c16H21 NAsI: C, 44.8%; H, 4.95"~. 6 (CDC13) 7.30 (10H, nult., ArH); 4,99 (1H, very broads., NH, exchanged with D20); 3.56 (4H, broad s., CH 2CH 2); 2.45 (6H, s., CH 3;.

Attempted prepar~tion of 2-(N',N'-dimethylamino)diphenyl­ amine (XXXV) via the reaction of 2-aminodiphenylamine with dimflt~.yl rhosnhone.te

o-Aminodiphenyl anine ( 2. 5 gJ and di met '.:yl phosphonate (7.5 G, 5 mole) were refluxed under nitrogen for 4 hr. The

::roduct W3.S cooled 8.lld poured into aqueous sodium hydroxide ;::olution ( 10f, 100 ril) 2nd the solution ,·:as •:,armed at 80° - 70 - for 1 hr. After coolinc, the mixture ·w2.s extracted with chloroform and the chloroform extract was dried and evaporated

The residual oil was vacuum distilled. b.p. 0 _4 122° (1.5 g, 49%).

' ( CDCl J) 6. 9 3 ( 9H, rrrul t. , ArH) ; 3 • 10 ( 3H, s. , Ax 2NMe) ; 2. 67

( 6H, s., ArNMe 2 ). o-Chloro-N, N-dimethylB.ni line o-Chloro8niline (25.7 g) and dimethyl phosphonate (44 g) were refluxed for 4 hr. The product was cooled, poured into aqueous sodium hydroxide solution ( 10%-, 400 ml) and the solution was warmed at 80° for 1 hr. After cooling, the mixture was extracted with ether and the ether extract was dried and evaporated. The residual oil was distilled. b.p. 206-208° (18 g, 58f) lit. 50 b.p. 208°.

Attempted preparation of 2-(N\N'-dimet~ylamino)diphen.ylamine via the reaction of 2-Chloro-N,N-dimet~ylaniline with aniline. Isolation of m-(N',N'-dimethylamino)diphenylamine Aniline ( 9. 3 g) was added dr opwi se to a suspension of sodamide (3.9 g) in a mixture of hexamethylphosphoramide (25 fil

nnd dry T.H.F. (30 ml) at 10-15° under nitrogen. The mixture w.qs stirred "..t room temperriture for 3.5 hr. o-Chloro-N,N­

dimethylaniline ( 7. 77 g) was added e.nd then sodamide ( 3. 9 g)

\·:rs added in small portions over 2 hr. The mixture ws:s - 71 - waxmed ~t 40° for 8 hr. After coolins, the mixture was poured onto ice and extracted with ether. The ethereal extract was washed with water, dried and evaporated. The residual oil was vacuum distilled. 1. b.p. 0 _4 42-46°, 7.8 g. 2. b.p.0 _4 60-150°, 0.2 g. J. b.p.0 _4 156-180°, 3.9 g. Fraction 3 crystallised on cooling, m.p. (petrol) 64° (3.9 g, 37%) lit. 51 m.p. 65-66°.

'(CDC1 3; 6.94 (9H, mu.lt., ArH); 5.50 (1H, s., NH, exchanged with D2 o) ; 2. 81 ( 6H, s. , NMe 2) •

Preparation of 2-(N',N'-dimethylamino)diphenylamine via the reaction of methyl iodide with 2-aminodiphe~ylamine Anhydrous potassium carbonate (5.2 g), 2-aroinodiphenyl­ amine (1.5 g) and methyl iodide (40 g) in benzene (40 ml) were refluxed under nitrogen and in the dark for 28 hr. The mixture was cooled and filtered and the residue was washed with benzene. The filtrate and benzene washings were combined and evaporated and the residual oil (3.2 g) was chromato­ graphed on alumina (140 g) using petrol-benzene (4:1) as eluent. Fraction 1. 2.5 g Pale yellow oil. The eluent was chaneed to benzere to sive fraction 2, 0.3 g, yellow gum. The eluent was changed to chloroform-benzene ( 1: 9 J to give fraction 3, 0.3 g, red oil. Fraction 1 was the desired product ( 2.5 g, 62%). It - 72 - could not be crystallised and was unstable in air and was hence characterised as its acetamide (see below).

£(COC1 3J 7.18 (9H, rrru.lt., ArH); 6.56 (1H, s., NH, exchanged with D20); 2.67 (6H, s., NMe 2). Fraction 2 was the monomethylate d amine.

~(CDC1 3J 6.89 (9H, rm1lt., ArH); 4.91 (1H, broads., Ar 2NH); 4.08 (1H, broads., ArNHMe); 2.80 (3H, s., ArNHMe). Fraction 3 was starting material (m.p., t.l.c.).

N-Acetyl-2-(N',N'-dimethylamino)diphenylamine

n Butyl lithium in petrol (1.6M, 5.2 ml) was added to

2-(N',N'-dimethylamino)diphenylamine (1.4 g) in ether (20 ml). The solution was stirred for 0.5 hr. and acetyl bromide (1.9 g) was added dropwise. The mixture was stirred for a further 0.5 hr. and hydrolysed with water. Sodium carbon~te vrns added to the mixture until the solution was basic to litmus. The ether layer was decanted, dried and evaporated. The residual oil was recrystallised from ethanol ( 1.0. g, 60%) m. p. 67 0. Found: C, 75.8%; H, 7-1%; N, 10.9%·

Calc. for C1f58 18N20: C, 75.6%; H, 7.1%; N, 11.0%. b(CDC1 3J 7.25 (9H, mult., ArH); 2.70 (6H, s., NMe 2); 2.09

( :m , s • , CH 1 CO ) . _) When the acetylatio n was 8.ttempted with acetic anhydride­ pyridine, only startine material was recovered. - 73 -

2-(N',N',N'-Trimethylammonium)diphen;ylamine p-toluenesulphonate 2-(N',N'-dimethylamino)diphenylamine (0.7 g) and methyl p-toluenesulphonate (0.61 g) were warmed at eo 0 under nitrogen for J.5 hr. The resulting crystalline mass was recrystallised from rnethaml-ether (0.5 g, 38%), m.p. 191°. Found: C, 65.9%; H, 6.5%; N, 6.6%.

Cale. for c 22H26N2so 3: C, 66.3%; H, 6.6%; N, 7.0%. b(CDc13; 7.26 (14H, mult., ArH and NH;; 3.71 (9H, s., NMe 3); 2.27 (3H, s., toluene CH 3;. Deuterium oxide exchange showed a one proton decrease in the integral in the aromatic region between f> 7. 63-7-42.

(p-Aminophenyl)diphenylarsine (XLII) (p-Arninophenyl)diiodoarsine hydriodide (12 g) 52 was ci.dded in small portions to a solution of phenylmagnesium bromide (69.2 g, 20 mole) in ether (300 ml). The mixture was stirred for 1 hr. and hydrolysed with aqueous ammonium chloride solution. The ether layer was decanted, evaporated to 100 ml and was washed with 10% hydrochloric acid. An oil, insoluble in either phase, separated. Benzene was added to Ji ssol ve the oil and the organic layer v,as separated, dried 2nd the solution was triturated with ether. The hydrochloride separated on cooling and was recrystallised f:rom methanol­ ether, m.p. 127° (5.0 g, 64;'). Found: C, 60.4fo; H, 4.7%; N, 4.1%. - 74 -

(:,0 ml) The hydrochloride ( 1.• 8 g) was dissolved in ethanol

.'"Jnd tre8t..:d with aqueous potassium hydroxide solution (20fj.

Thi'! mixture wr,s diluted with ,,.mter and extr~cted with ether.

The ethereal extract was washed 'Ni th 7ratcr, dried and evaporR.ted to r;ive a colourless oil ( :• .1 g, 91%) which could

!'lot be crystallised. (2H, s., NH , exchanged ~(CDC1 3; 7.25 (14H, mult., ArH); 3.53 2 rrith D')O). L

(n-Acetamidophenyl)diphenylarsine The arsine (0.26 g) and acetic anhydride (2 ml) in pyridine (2 ml) were warmed at 80° for 0.5 hr. The mixture was filtered \'TD s poured into water and the crystalline solid

0.nd recrystallised from aqueous ethanol (0.18 g, 61%,J, m. p.140° Found: 3-9%­ Cale. for c20H18NAs0: C, 66.1%; H, 5.0%; N, b(CIXa); 7.34 (15H, mult., ArH and NH); 2.10 (JH, s., cn 3co).

r-(Diphenylnrsino) diphen,vlamine (XL)

Sodqmide ( O. 24 6 ) wn :J added to ( p-mninophenyl) diphenyl­

arsine (2 gJ i!'l hexameth,7lphosphoramide (5 rrJ.J and dry T.H.F.

( 5 ml) and the mixtnre was stirred under ni troe;en for 2 hr. J-..omoben::ene ( 1 G, 1 r:io1e ,l in T. H.F. ( 2 !'il ) •."rts aided a_v:::3.

c:•.)l•o__•nide (0. 73 g; •::,..,,:-,, "CTd.ed in mmll rortions over 2 h:r. The The mixture :Jolu-t:iori ·vr:i;-, ·.·, 0 r-,1>:.~d ":J 45° ·-:mJ 3tirred for 1~' h:".'. The ···:--:2 cool:?d, ponred onto ice wd extracted with 'benzene. - 75 -

e.nd evaporated. b~nzene extrg_ct wg,s washed ·.vith water, dried on alumina ~h13 residual oil (2.4 6 ) was chromata-72.phed as eluent. Fraction 1, ( 100 g, 1.1.sing vetrol-benzene (9:1) to benzene­ :) • 45 g, white cr:,rstals. The eluen t ,'/3-S changed crystals. petrol (]:?J. Frriction 2, 0.5 g, pale yellow p!"oducts. Further elution gave a mixture of more pole...r g, 15%). Fraction 1. m.:). (light petroleum) 110° (0.45 NH absorption and the N.tT.R. T 11P. infrared 8pectru.m showed no spectrum showed only s.rom9ti,~ protons.

~~ss spectral 2n~lysis- Found: Parent 473-1132

Cale. for c1OH24NAs: Parent 473.1124. of fraction 1 A met hi odide was prepared by refluxing a sample m. p. · ( meth-?.nol-ether) 178°. 1vi th methyl iodide for 1 t; h.:r.., 3.05 (JH, s., CH ). '(CDC1 1) 7-3? (24H, mult., ArHJ; 3 Found: C, 6O.7~; H, 5.05%. H, 4.4 '.. c.,_1c. for c 31H27NAsI: c, 6O.5~; 7 diphf:mylarsine Fr 8.ct ion 1 r,as hence ( p-N, N-diphenylaminoph9nyl) 69° (0.5 g, Fr.·1ction 2 wa.s the desired arsine, m.p. (ethanol) -1 'NH stretch \>3360 cm •

Foun,1: Parent 397 .0817

C'.:'lc. for c24n20RAs: Pa.rent 397.0811. 5.45 (1H, s., NH, exchan,c;ed ~(CDCJ 3; 7.2,3 (1qH, rmtlt., ArH); ·:: i t h D,, 0 ; • 300 (24,800;. :\:-:lA.X (E., 211 ( 14,200), '.?40 (shoulderi(12,4OOJ, - 76 -

( p-F-PhP.nyl ami no;)heny:_l J diphenylmethylar so.n.t2!T~- iodide ( XLI; p-(DiphenylarsinoJdiphenylamine (JO me) and methyl iodide

( 42 mg; in qcetoni trile ( 2 ml) were all owed to stand R.t room temper 0 ture in a se:iled flask for 13 days. The solvent was removed ~nd the residue recrystallised from methanol-ether, m. p. 215° ( 110 mg, 885"'). The salt was insoluble in chloroform. Found: Cale. for c25tt 23 NAsI: C, 55.6%; H, 4.2%; N, 2.6%. 0); 7. 19H, b( d6 U1SO) 9 .00 ( 1H, s., NH, exchanged with D2 80 ( mult., ArH); J.01 (3H, s., CH 3). ( 4 6 9, oo ) , 3 1 5 ( 27 , 100 ) • }-. mnx (l ) 214 When the arsine was refluxed with excess methyl iodide for 1.5 hr., t~e product had m.p. 184-190° and contained 67% N-methylnted arsonium salt (from N.M.R.). - 77 -

SECTION 2

SYNTH:SSIS OF HETEROCYCL:ss WITH

A STEREOCHEHICALLY RIGID HET2RO ATOM

2.1 Introduction

Tryptycene (LIX) is a novel molecule in which the phenyl rings are mutually inclined at an angle of 120°, and the bridgehead carbon atoms are rigidly held in a tetrahedral configuration. It should be noted here that the systematic n.,,me for tryptycene is 9, 10-dihydro-9, 10-o-benzenoanthracene; however the tryptycene nomenclature, introduced by Bartlett 53 et. al. will be used thl'oughout this Section vrhen naming compounds of this class, to better illustrate the inter­ relntionships between the various members.

(LIX)

Only two members of this class of compounds a.re known ( see below; in which one or both bridc;ehead CH groups a.re repl"l.ced by h8tero atoms~ and it was of interest to synthesise other heterocyclic members of this class. - 78 -

The ph0sphorus compounds were of particular interest because the quaternary se,l ts from such phosphines should be stereochemically rieid, being fixed in a tetrahedral config­ urriti0n. Hence t(1e reactions of these salts should provide ,'?.n interesting study, particularly those reactions which are believed to proceed via a trigonal-bipyramidal five-membered transition state or intermediate, such as alkaline hydrolysis. 54 The dihydrophenophosphazine system (LX) appeared to be a useful starting point, since it seemed likely that an intermediate such as (LXI) could be cyclised to give azaphosphatryptycene (LXII).

(LXJ (LXI) (LXII) 10-Substituted-5,10-dihydrophenophosphazines (LX, R = H, R' = alkyl or arylJ have not been reported in the literature

8.nd some new synthetic 9-pproaches to this class of compounds were examined (see Section 3). 10-Substituted-5,10-dihydrophenarsazines (LXIII) are readily prep:-tred ( see Section 1), and it was decided to develop 1. suitable cyclisation reaction with the phenarsazine - 79 -

system as a model for the phenophosphazine system.

(LXIII)

A number of heterocyclic syntheses have been reported in which an aryl h,q,logen group was cyclised onto a secondary

a::1ine f3rrup, utilising a benzyne-type reaction. Thus, for example, N-methyl-2-(o-chlorophenyl)-ethylamine (LXIV) was converted to N-methylindoline (LXV) in 71% yield by a nixture of lithium diethylamide and phenyl lithium. 55

PhLi

(LXIV) (LXV)

Wittig and Steinhoff prepared azatryptycene (LXVI) by the action of potassium amide in liquid amnonia on n_ ( o-chlol"ophenyl) acridan ( LXVII) in a similar react ion. 56 - 80 -

H

(LXVII) (LXVI) 10-(o-ChlorophenylJ-5,10-dihydrophenarsazine (XII) seemed a useful and readily accessible starting material (see Section 1) for the preparation of the azarsatryptycene ( LXVIII) .

(LXVIII) Sodrunide in hexamethylphosphoramide has been recently reportea10 to give high yields of secondary and tertiary [1J!'lines from halobenzenes and aromatic amines via a benzyne­ type reaction wd it was proposed to attempt the cyclisation of (XIIJ with this rea[;ent. If it could be prepared, (LXVIII) would be the second n.rsenic analog of tryptycene. Diarsatryptycene (LXIX) was first reco~nised by McCleland and Whitworth, 57 several years before tryptycene itself was prepared. - 81 -

(LXIX) Several routes to (LXIX) are known. 1.1cCleland and Whitworth found that when phenylene-1, 2-diphenylarsinic acid (LXX; was heated with phosphorus trichloride and the product was vacuum distilled, (LXIXJ sublimed out of the reaction in 33~ yield.

Ph I As-Cl ©( ~CLXIX) Pel~ ) As-Cl ~h (LXX) (LXXI) Phosphorus trichloride presumably reduced the acid to phenylene-1,2-diphenylchloroarsine (LXXI) which was cyclo­ dehydrohalogenated on heating. "Arsanthrene oxide" (LXXII), which is prepared by the action of base on 5,10-dichloro-5,10-dihydroarsanthrene (LXXIII), 58 (and whose structure is in doubt), 2 gave (LXIX) and arsenious oxide when it was heated in a current of carbon dioxide at pressures slightly less thnn atmospheric. 57 - 82 -

(LXXIII) (LXXII) Diarsatryptycene was also formed in the preparation of (LXXIIIJ. Kqlb first prepared (LXXIII) by the reduction of o-arsonodiphe~ylarsinic acid (LXXIV) with sulphur dioxide 8nd hydrochloric acid. 58

sCL ~COXOH>2 2 S02/HCl > CLXXIID+CLXIX) + roc ~CO)OH Cl I I Ph Ph

(LXXIV; A small amount of an insoluble compound was formed as rr by-product of this reduction, but was not identified. !,lcCleland and Whitworth showed that this compound was (LXIXJ, ond the reaction vras later modified by Chatt o.nd Mann59 to increase the yield of both (LXXIII) and (LXIX). Benzoazatryptycene (LXXV), 60 which is closely related to the tryptycene cl3ss of compounds, is the only other compound of this type which has a hetero atom at the bridge­ he qd. Its syn thesis is briefly outlined in the fol lowing - 83 -

Poly-phosphoric acid

(LXXV) - 84 -

2.2 Results and Discussion Several experiments were carried out to determine the optimum conditions for the reaction of (XIIJ with sodamide in hexamethylphosphoranide. When 2 moles of sodamide were reacted with (XII) for 67 hr. at 45°, starting material was recovered in 70% yield. Starting material was also recovered in high yield when 4 moles of sodamide was used and the reaction was heated at 45° for 3 hr. However, when 4 moles of sodamide was used ~nd the reaction was heated at 45° for 67 hr., only a trace of material of Rf identical to starting material (by T.L.C.J remained. Four compounds could be distinguished and these were isolated by column chromatography. The least polar fractions consisted of two compounds r1hich comprised Sl· 1~:' of the reaction product. T.L.C. and

:-r .I-LR. and ultraviolet spectra suggested that the two

compounds were biphenyl 8nd triphenylanine, and G.L.C. provided supporting evidence. The origin of these products rcmnins obscure though it is clear that cleava6e of As-C bonds is involved. 10-Phenyl-5, 10-dihydrophenar sazine r.ras also isolated

from this re~ction in Q.g_. 2% yield. The origin of this ?roduct is '.1.lso unknown, thouc;h it should be noted th9.t .'ii tti: e:.nd Stei!'Ihoff isol'.:l.ted a small yield of 9-phenylacridan - 25 - i r. the y;rep'"l.!'2-tion of 2,z~tryptycene (L~·:'lIJ fron r:· - ( o-chlo:rophenyl J c:cri de 11. 5 6

Th2 m~jor ~.roduct of the reaction of (XII) vrith

.: od ..,midc, i ~olo.t ed in 70:, _yield, was not the de sired tr~n~tyr:ene (I.T'TIII) but was identified as the secondary

":r:: in'? oxi <"le ( LLXVI 1 •

~h ©C© I 0 ©J::)gI I Ph

( LXXVI)

The m2.ss 2p,2ctrum of (LXXVI) h8.d a molecular ion peak ~t m/2 65~ ind nccurate mnss mqtchinc on this peak confirmed

1~e mo t Jr cuJ ~r f or!nulr. as C., 6H26N 2As 2o. The compound was converted into 5-p~en~-10-ethoxy-5,10-dihydrophen~~sP~inc - :6 -

(LY.XVII)

The identity o: (LXXVI J w~s confirmed by its conversion n,-, follo·.v~, +c_, e compound synthesised uner-uivocally. The e tr..oxy deri v~J ti,., e ( LXXVII) was r2 acted with m0thylmagne sium

i c dicle to give the 10-methyl derivative (LXXVIII) which was

quaternised v.'i th methyl iodide to give the arsoniurn salt (LXXIXJ. The salt (LXXIX) was prep91•cd unequivocally by the re action o:: 10-methyl-5, 10-dihydrophenar S8.zirie with sod amide

~na bromoben~ene to ~ive the 5-phenyl derivative which was q_u~.1.ternised with methyl iodide to give the salt (LXXIX).

The sc1,l ts o bt3.ined b:,r these two routes rrere identic ol in every respect. Thi.s series of reactions is outlined .in the ~h

ILXXVI) EtOl::I > ~)QJ I Me (LXXVIII) 1Mel Ph H I 2+Ph8r > ~~ 0 ~N'r()t -~)NoNH r ~~ 11) Mel ~j ~e Me Me

(LX:XIX) with in the reaction of (XII) Tf:.e i~ol3_tion of (LXXVIJ the sphor9Jl1ide suggests that so dnmide in hex8,methylpho must have been an interm edia.te ,,., ~ar s3tryptyc8ne o.nion ( lX:XXJ

j r. tte re '.:let ion.

(LXXXJ It i~ difficult tc see how the phenyl 3roup could (LXXX) i::.i::r0te froT!l 8..rrienic to ni~ror~en unless tf,.e o.nion The •;r3.s formed i1: the roo.ction and then reacted further. colour 2.·o?.ction mixture prior to hydrolysis ·.vas a deep red that arsenide end it •,-r2s thow;ht 1.JOssible, though unlikely, In ,' Dions r.1ight have been pre sent to cause the rod colour. of formation -;n 8.ttempt to 6ain an insight into the mechanism mixture of ( LXXVI), methyl iodide was added to tho reaction the just prior to hydrolysis. The dark red colour of rras still the major ''lixture "J8.S disch2.r ged, however (LXXVI) nroduct isol~ted after hydrolysis. There appeared to be some differences in the mir:.or T.L.C. products o:)t"tir:.cd by this variation of the reaction. s- indicate a th8.t bi phenyl and 10-phenyl-5, 10-dihydrophenar absent and c zine, which were both isolated previously, were minor th8t triphenylGmine was still present. The principal of the minor ~ roduct was different (by T.L.C. J from any (LXXXI; products obt!l.ined previously and was shown to be c c ont9.1llin8.ted with a small amount of '.:>n unknoYm dimeri

~e ©r:)QJ I Ph - eg -

The !7-met:i.yl compound (LXXXI; was prey.red independently with by the reactio!'l of 10-phenyl-5, 10-dihydrophen2..rsazine in a sod8mide "lnd methyl iodide 9,nd presumably arises ':ti sodaJ!lide s imil -:1r m~nner in the reaction of (XII) th followed by methyl iodide workup. the In the light of these results it seems likely that in the azarsatryptycene 8nion (LXXXJ is an intermediate formation o~ (LXXVI) from the reaction of (XII) with excess of sod2~mide. The anion is presumably cleaved by the which on sodamide to ~ive the aminoar sine dianion (LXXXII J hydrolysis 8ives

{XII )

( LXXXII)

Cleava~e of terti~:1.ry arsines by sodamide does not The form- ~: ppe8.I' to h3.ve been investigated to any extent. sodamide 8.tion of N-phenylpii:;eridine from the reaction of been in boiling piperidine with phenylarsonic acid has of ~eportea. 61 This reaction obviously involves cleavage forward. the As-C bond but n detailed mechanism was not put Aminoarsines nre readily hydrolysed. Diphenylamino­ on nrsine, for exan~le, formed by the action of ammonia - 90 - diphenylchlora.rsine, gives diphenylsxsine oxide (LXXXIII) very readily on hydrolysis. 62

Ph 2As0AsPh2 (LXXXIII) The seconds.ry arsine oxide (LXXVI) ,,.,as converted to the 10-chloro compound (LXXXIV) by treatment with hydro­ chloric acid. ~

~Cl

( LXXXIV) Chloroarsines of this type have often been cyclised by elimination of hydrogen chloride and in fact this type of reaction was proposed to explain the formation of dinrsatryptycene (LXIX) from phenylene-1,2-diphenylarsinic ~.cid (LXX). 2 However, (LXXXIV) was recovered unchanged rrhen vacuum sublimed or heated at 200° for 6 hr. at atmos­ pheric pressure. The aza~satryptycene (LXVIIIJ was eventuaJ.ly obtained in 48~- yield when (XII) was refluxed in ether with 1.25 moles of lithium diethylamide and 1.75 moles of butyl lithium for 5 d~ys. Support for the tryptycene structure was gained from the infrared spectrum which showed no HR stretching - 91 - b -::.nd, 9.11d the mass spectrum which showed a strong parent ion at m;e 317. The product showed T.L.C. behaviour expected of an arsine, had a hi~h melting point (233°) and vacuum sublimed very readily. The ultraviolet spectrum showed a strong end absorption

~t 218 mµ and no other bands were present in the spectrum. This is in marked contrast to the spectra of triphenylamine 8.nd triphenylarsine where strong absorption bands are observed due to interaction of the lone pair on the hetero 2-torn with the phenyl rings. 31 The spectrum of ( LXVIII) hence indicates that no such interaction occurs in azarsatryptycene. This would be expected since the hetero atoms, which are in an Rpproxim8tely tetrahedral configuration, should be rigidly held in the cage structure of (LXVIII), such that no inter­ action of the lone pairs, (which occupy the fourth position of the tetrahedron), with the phenyl rings is possible. It should be noted here that the ultraviolet spectrum of ( LXVIII) shows some differences from the ultraviolet spectrum of tryptycene (LIX) and azatryptycene (LXVI). 56 The ultraviolet spectra of these two compounds are virtually identical qnd show two weRk bands (£ ~- 3,500) at 270 mµ 2.nd 278 mp. No such bRnds are visible in the azarsatrypty­ ccne spectrum, though some structure is visible on the low energy t..,i1 of the 218 rnµ band, at ~- 265-280 rnµ. - 92 -

Azarsatryptycene reacted with sodamide in hexamethyl­ phosphoramide to give a high yield of the arsine oxide

(LXXVI) after aqueous workup. This reaction provides strong supporting evidence for the mechanism proposed for the formation of the arsine oxide (LXXVI; from the reaction of

10-(o-chlorophenyl)-5,10-dihydrophenarsazine (XII) with sodamide in hexamethylphosphoramide. Sasse and Jackson have demonstrated that triphenyl­ phosphine and triphenylarsine are quantitatively cleaved by Raney nickel to give benzene, while triphenylamine is unaffected. 63 When (LXVIII) was reacted with Raney nickel, a 31% yield of triphenylamine was obtained and 50% of starting material was recovered. The compound was unaffected by 3 do,ys reflux with an excess of sodium ethoxide and, rather surprisingly, was unaffected by reflux for 3 hr. with 485;; aqueous hydrogen bromide or with 485"{ hydrogen bromide in acetic acid, reasents which usually cleave aryl arsines quite readily. 27

Reaction of (LXVIII) with concentrated nitric acid gave the arsine oxide (LXXXV).

( LXXXV) - 93 -

The resistance of (LXVIII) to nitration under these conditions also provides evidence that the lone pairs on both the nitrogen and arsenic atoms do not interact at all ·:,i th the phenyl rings, for triphenylarsine and triphenyl­ nmine are both nitrated v1hen treated with nitric acid. 64 , 65 Azarsatryptycene reacted with an excess of bromine in chloroform to give a very unstable oranr.;e crystalline product which smelt strongly of bromine and which decolourised on standing in air. On attempting to obtain a melting point, the comnound. decolourised at -ca. 180° and the residue melted at the melting point of the azarsatryptycene. The compound reacted with alcoholic potassium hydroxide or even with aqueous ethanol to give the oxide (LXXXV). A bromine Gnalysis (as AeBrJ indicated that three bromine atoms were present and the formation of the arsine oxide on hydrolysis indicates that two of the bromine atoms were attached to the arsenic atom. The position of the third bromine atom can only be a matter for speculation, but it is possible that it is bonded to the nitrogen atom to give an aminium salt; 66 such thnt the product has structure (LXXXVI).

( LXXXVI) It might be expected th~t (LXVIII) ,7oulu be considerably morR b~sic th::1n triphenyl 3,mine, since the lone pairs on the hetero ato □ s do not inter a.ct with the phenyl rings, and mic'.":ht form e quaternary sru. t fairly readily. However, 22'U'satryptycene resisted ~11 attempts at quaternisation. Ar; noted 8bove the compound was unaffected by 48~i hydrobromic

2.cid, a reaeent which is usually used to cleave a.ryl 2.r sines. It might have been expected that, even if cleavage did not occur, aZ8Xsatryptycene might have formed a hydro­ bromide salt under these conditions. The compound ~as recovered unchan3ed ~hen refluxed with methyl iodide for 20 hr., or when allowed to stand for 2 d2ys with 9.n excess of triethyloxonium fluoroborate in c1 ichloromathane. :,Yi ttL:-; 9nd Steinhoff used silver fluoro­ bor2te-methyl iouide to successfully form an N-methyl fluoroborate of azatryptycene (LXVI). 56 Ho\':ever (LXVIIIJ

··r.'"' s recover ad unchan0ed ,·,hen treated r.ri th this reagent. Di8.1's'3try_0tycene (LXIX) is also very resistant to

GU.'.:. tcr:r.i :J'"'tio n, be in:3 nn r:ffe etc d by ~)rol on.~ed reflux \"Ti th :.:8thyl ioL1ide. 57 ::ann and Bqker were c-.ble to form 2 y:-,cno-:::etho p-tclluenesulphonr!.te of (LXL(J by heating it nith o G'7 0 xc,) s s of mot!iyl )-tol nene sul;_)hon2.te at 180 for 4 hr. ' ·,·,·11en the .'1'.3:::.r;;n.tr:rpt::,rcene ,·:ns reacted un(er these corn1i tion.:; of the "':;,,1 tro.hedral con:'i,--;t1ra tion on cd the r -:;'.-le ,3.rseni c or

-:;hn, nitroP,~n a,~'.)r:1, \·rhich is necessary for quaternis-3.tion,

is m·1de very di.fficul t by the stereochemistry of azarsa­ tryptycene. o The norm,u C-T,r bond 1 1:::!nt;ths [,2.,:_;. 1.37 A in 12 1C--ch"]1wo-5, 1O-dihyurophenarsazine (I) J are small compared 0 to ~he A:=,-C bond 1~n~ll [e.g. 1.99 + O.•)19 A in cacodyl ( , ] 68 su1phiie IX) . Hence, because of th,:; :-:,re sence of the 2m2ll C-N bond lengths ~tone apex of the cage structure of 2.'.3D..r sa tryptycene ond the lar ~e As-C bond len[;ths at the other apex, 2zarsatryptycene would be exp9cted to be c1 i st orte d sor:1e 1.vh~: t from the ideal c:eome try ob served in tryptycene itself. This distortion wm1ld be expected to

:1~·.ve the result of mfcdtin.s the C-As-C bond an:~les less than n0rm 0 1. The C-As-C angle in 1O-chloro-5, 1O-dihydrophenars-

2.zine (I; is 0 7°, 12 i=md if the angles in 8,zarsatryptycene

~r•? sm'?ller thf'n this, then the rigid st8reochemistry of the molecnl8 1·1ould m,dw the assumption of the tetrahedral c onfi:~UI'7: tion on m.· se n:i.c energetically very unfavourable, r,nd coulu ;X~)l 0 in the difficulty in qu2,ternisin& azi=t.I'S8.­ tryptycene.

Sir:1iln.r re'."\.son:i.nc; c'.Ul be a1::ip1ied in the c.:,,se of the

S-!'J-C bonJ an.::;L~s in n.zarsatryptycene wd miGht explain why C'U~.ternis?ti.;r.. of tbJ nitro_:en atom does not occur either. If the 2bovc rcnsoning is valid, it perhaps explains the difficulty in formj_ne R quaternary :3riJ. t~ but it is rlifficul t to see ,.·rhy azarsatryptycene forms e. compound with bromj_ne in which t'.'lo o:: the bromine atoms 2.re att2.ched to the ?J' se ni c ?tor.1, :.-ire sumably conferri.n c:: t:\ tri <3on,Jl bipyrRITiid8.l confi;:_,'Ur1tion on the arsenic atom. This compound ··,oulcJ be e·{pected to be considerably more strained than a '!uatern::try sRl t vtht~re the arsenic atom is in a tetrahedral c onfi0ur ." t ion. Diar S8t!'YlJtycene ( LXIXJ shows a similo.. r set of o.pparently anomalous properties. It forms a tet!'abromide

\'rhich ,~iv(~s 8 dioxide on hydrolysis, 57 but only forms a mono sr1l t even under very forcing conditions. 67 An X-ray study of both q7,arsatryptycene 3.nd (LXIX:J and of their ue ri vri.ti ve s would clearly be of consider'.:'.ble int ere st. The mass spectru1:1 of ( LXVIII) sho'.'.'ed some interesting fec1tnres 8nd the principal peaks 8re listed in Table 7. The P-1 peak is the most abundant ion in the spectrum ~nd in this respect the spectru.,n is like that of tryptycene ( lIX) itself wh=:;re the P-1 ion is the most abundant. 69, 70 'r!F] P-1 pen.k i.n t!'yl)tyce ne was originally assigned to a ,: tr1.1cture in which "· hydrogen rc1d ical h8.d been lo st from the b!'id,~ehead CH 7our to .'~ive a brids~eh8ad ccU'bonium ion. 69 TABLE 7

70 eV :iP._ss S"9'?c-4;rum of A~arsatry;;itycene (LXVIIIJ

------·----- Relative Abund811ce

70 -, 15 100

242 5 241 25 240 6 158.5 4 158 4 157 4 120. 5 4 ------·------

However, a recent study using deuteriu.rn labelling has shown that the hydro:en radical is lost, not from the bridgehead, but from one of the phenyl rin:;;s and an ion sue h as ( LXXXVII)

suggested to 2ccount for the P-1 peo.k. 70

HC=C-CH=CH-C~C-

or I-:IC=C-C=CH-C=CH I

( LX)CX'!II) - 98 -

The doubly chn.r~ed ions at m/e 158.5 (P/2) and probably m/e 158 (P-1/2) in the :nass spectru;n of az3.rsatryptycene indicate the st'J.bili ty of the ring system. Similar doubly ch2rged ions are observed in the spectrum of tryptycene. The rn/e 241 pe~k is of considerable interest, for this is the molecular wei.r;ht of the phenA.rsazine ion (LVII) which

W? s postulated by Buu-Hoi et al. 37 in the m,g,ss spectrum of 10-chloro-5,10-dihydrophenarsazine (I). Accurate mass matching of the 241 peak in azarsatryptycene showed that the ion was not (LVII; but corresponded to c1sR 11N+. This peak h::ts been tentatively assigned as (LXXXVIII). +•

(LXXXVIII)

This ion bears some similarities to a product (LXXXIX) isolated by Wi ttii 2nd Steinhoff from the photochemical renction of azatryptycene (LXVI). 56

(LXXXIX) - 99 -

J... met ?.st9.ble ion at .£g_. m/e 186 could correspond to

either P ➔ (LXXXVIII) or to P-1 ➔ (LXXAVIIIJ. If the P-1 io!'l of azarsatryptycene is of a similar structure to the P-1 ion ( LXXXVII) postulated in the mass spectrum of tryptycene, then it is difficult to see how this ion could fragment to ( LY..XXVIII). A possible fragmentation pat!-n·,2-y from the parent ion to (LXXXVIII) is outlined below. ~- ©( 0 ) ©C© t ~ + 1 ~- 0. C(~I~ < As •• ~As 0.

)

\. (LXXXVIII) - 180 -

If the P-1 ion of r,_zers8.try ptycene is not of 2. simil ':U"

tyre to ( LXXXVII J , but is ~~ structure such 9.3 ( ZC 1, then it

is possible to ::ormul::~te r1 pathway from (ZC) to (LXXXVIII)

Jimply by extrusion of the arsenic atom, by a similar process to that outlined in the previous scheme. +

(XC) - 101 -

2.3 Section 2. Experimental Index Page Attempted cyclisation of 10-(o-chlorophenyl)-5,10- 102 dihydrophen8.rsazine with sodamide in haxamethylphos­ phormnide. 2. Authentic 5-phenyl-10,10-dimethyl-5,10-dihydrophenazar-104 sonium iodide (LXXIX). 3. 5-Phenyl-10-methyl-5, 10-dihydrophenar sazine and its 105 methiodide via 5-phenyl-10-ethoxy-5,10-dihydrophenars~ azine. 4. t1ethyl iodide workup of attempted azarsatryptycene 105 preparation using sodamide in hexamethylphosphoramide. 5. 5-Methyl-10-phenyl-5,10-dihydrophenarsazine (LXXXI). 107 6. 5-Phenyl-10-chloro-5,10-dihydrophensxsazine (LXXXIV). 108 7. Azar satryptycene ( LXVIII) . 108 8. Azarsatryptycene oxide (LXXXV). 109 g. Reaction of azarsatryptycene with bromine. 109 10. Attempted quaternisation of azarsatryptycene. 110 11. Reaction of azarsatryptycene with sodamide. 110 12. Reaction of azarsatryptycene with Raney nickel. 111 - 102 -

Attempted cyclis8.tion of 10-(o-chlorophenyl)-5, 10-dihydro­ phenars2zine with sodamide in hexameth.ylphosphorarnide. Sodamide (0.55 g, 1 moleJ was added to 10-(o-chlorophenyl-

5,10-dihydrophenarsazine (5 gJ in hexamethylphosphoramide

( 2 5 ml) and T. H.F. ( 10 ml) • The mixture was stirred under nitrogen for 2 hr. and sodamide (1.65 g) was added in small portions over 2 hr. T. H.F. ( 10 ml) was added and the mixture was warmed at 45° for 65 hr. The dark red solution was poured onto ice and acidified with 2M hydrochloric acid. The solution was extracted with chloroform and the chloroform extrn.ct was washed with v,ater and dried. Evaporation of the sol vent ~ave a brown gum ( 4. 9 gJ which was chr omatogr aphed on alumina ( 200 g) using benzene-petrol ( 1: 4) as eluent. Fraction 1, 0.086 g, colourless crystals. The eluent was gradually increased in polarity to benzene to elute fraction 2, 0.12 g, pale yellov1 crystals. The eluent was further incre~sed in polarity to benzene-chloroform ( 1: 1) to .elute frnction 'l., 3.25 g, pale yellow crystals. Further elution ~sve fraction l toeether with base-line material. Fraction 1. T.L.C. in benzene-chloroform (9:1J gave only one spot. In bern:ene-petrol ( 3:7) it separated into two spots which corresponded to biphenyl and triphenylamine. G.L.C. confirmed this observ~tion and the ratio of peak hei.n;hts indic::ted a 5:2 rntio of biphenyl to triphenylnnine. - 1U J -

:7.M.R. (CDC1 3; of the mixture supported this ratio. The triphenylcmine was isolated by recrystallis-:1tion of the ~ixture ~rom petrol, m.p. 127° lit. 50 m.p. 129°. No depression of mixed n.p. The ultraviolet spectrum of the mixture exhibited \ 243 mp and 29 3 JIil (lit. 8 A. 246 mµ ·max max 31 for biphenyl ~nd A.max 297 mµ for triphenylamine). Fraction 2, m.p. (ethanol) 147° lit. 16 m.p. for

10-phenyl-5,10-dihydrophenarsazine, 148°. No depression of 7ixed m.p. Infrared and ultraviolet spectr::', were identical

':ii th an authentic sample. Fraction J, m.p. ( ethyl acetate)' 253 0 . Colourless n e e d 1 e s ( ? • 2 5 g, 70 r;'c) • E::; s s spectral annlysis. Found: Parent 652.0481

Cnlc. for c36H26N2As 20: Parent 652.0476. A s~unple recryst'.tllised from ethMol gave 5-phenyl-10- ethoxy-5, 10-dihydrophenoxsazine (LXXVII), m.p. 144°, colour­ less fl2.kes which slowly turned yellow. Found: C,66.J5; H, 5.0; n, 3. Gf Parent ion 36:,

Cal c. for c20H18~1As0: C,66.15; H, 5.0; I'T,J.9% Parent ion 3 63 ~ ( CDCl J) ( 1 JH, mul t., ArH); ( 2H, J Qf"'JT '. 7.30 3.27 ou2.rtet 7IIz, ,., ·2 I ' C • n 5 ( 3H , tr i 1• l ct J 7 E '.:: , CH J J •

T!1e ethoxy conpo'..lnd r,•r:s converted h'lc\: to tl--ie o..rsine

::.·'"'d'u'in~ the voJu:.:e 0f :-:olvent to :,ne-thi1•r1. ~he oxide - 104 -

.'.uthentic 5-nhP.11;rl-12·, 1C-dio0th.yl-5, 10-c1ih,ydroi,hen3.z-

:-:-r::::;on1um• • lO a·l d e (-'r7TV'lw.. 1.. ... ,',)

Sor3...,mir1c (C). 1 --;J w:1_:' -:ldded to 10-netbyl-5, 10-dihydr-J-

,.,_.. _3 ~.f11Jed ir ~n,,lJ r,orticn:J over 2 hr. The r.1ixture w2s

::-:tirrea r't room tenpcr -:,_4-;-ure for 18 hr. ~~nc the r:iroduct vms poured onto ice ~na extracted with ether. The ether extract

·:,;'.1..s wnshcd with w3t2r, dried and evapor2ted to give an oil v:hich was chrom.'"'to:-:;raphcd or: Rlumina ( 16 g) using benzene­ petrol (1:4) as eluent. 0.22 g of a colourless of Rf 0.8

( chloroform) '>'ras eluted. Ful'tber elution cave 0.1 g of startin:; materiol ~md some more pol2.r p1•oducts.

The Rf 0.8 mc:1terinl w.qs quaternised rlith an excess of methyl j odide ?,nd the soJ t was re cryst:c_,_llise d fro:r.i methanol-

( ~- 0 ether ,0.22 c, over~:ll yi?.ld 31 1 '.J), m.p. 245-246. Fonnc1:

6(C:Y~l 3 J 8.5: (2II, mult., ArE); 7,42 (0H, nillt., ArH); C.57 ('.?~!, ri1U~t., ArH); '.?,?5 (6H, s., CH 3).

/'.T:1~"{ (£) 209 (50,400), 276 (22,100), 305 (14,900), 323

( 1C,400), 1 ~5 (shoulder) ~,900. - :05 -

1 0-ethoxy-5, 10-dihyclro phenar s8.zine

The etr..oxy compound (0. 27 gJ nas ~clded to a solution of r.-:ethylm'1r,nesiur.i iodide (0. 62 e, 5 mole) in ether ( 10 mlJ.

The mix+,ure ,·,~s reflu:i:ed for 1 hr'., cooled Dnd hydrolysed nith aqueous amr.1oniur.1 chloride solution. The mixture was diluted Yri th ether end the ether layer ,·rns dec.:i11ted, washed

1:ri th vmte:r <1nd dried. 3vaporation of the solvent gave a solid which was rAcrystalJised from ethanol (0.13 g, 50f),

:T:.p. 114°.

Found: C, 68.4%; H, 4 ■ 9%; N, 4 ■ 4%-

C8lc. for c1~H 16NAs: C, 68.45%; H, 4.8fo; N, 4.2%. d(CDC1 5J 7.31 (1:,H, mult., ArH); 1.17 (3H, s., CH 3). "'max (E) 213 (~2,200), 281 (23,000), 307 (shoulder) (9,400).

A met hi odide was prA pared by ref luxinz a sample of the arsine ,·,i th m0thyl iodide for 1. 5 hr'., m. p. ( methc.nol-ether) 248-9°.

No depression of mixed m.p. with 3Uthentic 5-phenyl-10, 10- dir.iethyl-5, 10-c1ihydro:1henazarsoniun iodide. N.I

'i,:ethyl iodide workup of attempted cyclisati.9_~ of

10-( o-chloro rhenyl; -5, 10-dihydrophens.r s2.zine nit h sod amide in h~xametcylphosphorBmide

The re qction ,·.rr.s cn.rrie d out as previously described

"l'lc1 1,·1i th the S"'T'le ouantities of reactqnts. After stirring

.,_.. c r 6 5 hr . ~- t 4 5 O, !TI et hyl iodide ( 4 . 1 5 ~-:; in T . H. F . ( 1 5 ml J - 106 - was added to the dark red solution. The colour lightened to yellow. Tbe mixture was stirred for 15 min. at room temperature, hydrolysed with water and extracted with ether. The ether extract was washed with water, dried and evaporated

to give a brown gum (5.0 g). T.L.C. in benzene-chloroform (9:1) showed spots ot Rr o.8 and Rf 0.3. The Rf 0.8 material was ot similar Rf to triphenylamine and the Rf 0. 3 spot corresponded to the previously isolated arsine oxide. There was no spot corresponding to starting material or to tbe 10-phenyl-5,10-dihydl'ophenarsazine which was isolated in the previous experiment. The product was chroma.tographed on alumina (200 g) using petrol-benzene (4:1) to elute fraction 1, 0.34 g. T.L.C. in benzene-chloroform (9:1) gave one spot Rf 0.8. The eluent was increased in polarity to benzene­ chlorotorm (1:1) to elute fraction 2, 3.6 g. T.L.C. in benzene-chloroform (9:1) gave one spot Rf 0.3. Purtber elution gave baseline material. Fraction 2, m.p. (ethyl acetate) 252°. No depression of mixed m.p. with preYiously isolated bis(5-pbenyl-5,10- dihy-dl'ophenarsazine) oxide. The ethoxy derivatiTe was also identical. to tbe previously isolated ethoxy compound. Praction 1. T.L.C. in benzene-petrol (3:7) showed this fraction to be a mixture of at lean four products. None of these corresponded to biphenyl, while one had similar Rf to triphenylamine. The major spot (Rf 0.3) was isolated by - 107 - preparative T.L.C. 0.16 g, m.p. (eth2.nol) 102-105°.

6(CDC1 3) 7.13 (11.6 sq., mult., ArH); 3.34 (2.4 sq., two nlmost co-incidental sinelets, m1e). The mass spectrW!l gave peaks at.£@:· 648, relative Qbundance 1%; and at 333, relative abundance 88%. These results suggest a mixture of 5-methyl-10-phenyl-5,10- dihydrophenar sazine (I.1. W. 333) and an unknown, probably dimeric product.

5-Methyl-10-phenyl-5,10-dihydrophenarsazine (LXXXI;

Sodamide (0.1 [!,) was added to 10-phenyl-5, 10-dihydro­ phenarsazine (0.8 g) in hexamethylphosphoramide (5 ml) and the mixture was stirred under nitrogen for 2 hr. Methyl iodide (0.25 ml) in ether (2 ml) was added to the orange-red solution and the colour was discharged. The mixture was stirred for 0.5 hr., hydrolysed with water and extracted with chloroform. The chloroform extract was dried and evap­ orated and the residue was recrystallised from ethanol (0.42 g,

5o r;f);' ' m.p. 140°. Found: C, 68.2%; H, 4-9%; N, 4.6%.

Cale. for c19H16NAs: C, 68.45%; H, 4.8%; N, 4.2%. 6 ( CDCl J) 7. 12 ( 13H, mul t. , ArH); 3. 3 3 ( 3H, s., NMe) . "'r.1.a.X (c) 221 (32,100), 213 (11,000;, 300 (9,900), 335 (6,600). - 10~ -

5-Phenyl-10-c hloro-5, 10-:-dihydroph enar so.zine ( 1:0..xr ·r J Hydrochloric 8-Cid ( 10::J was added clropYr.i.se to a

::nsponsion of bis( 5-phenyl-5, 10-dihydropheno..rsazine) oxide

( 0. 1,4 ::;J in acetone ( 10 ml). A pale yelloi:r solution resulted

~na the 0_ddi tion of further acid precipitated the chloro­

~rsine. The product WRs filtered and recrystallised from cnrbon tetrachloride (0.26 g, 70%), m.p. 178°.

Found: c, 61.05".;; H, 3. 9 5;~; N, 3-95%- ") 7

Azar sRtr.yPtycene ( LXVIII)

n Butyl lithium in petrol ( 81 ml, 1. 6LI, 3 mole) was added to 10-( o-chloro:7henyl J -5, 10-dihydrophenarsazine ( 15 g) in ether ( 750 ml) containing diet-hylar.iine ( 3. 7 g, 1. 25 mole) . Tile mixture wc1.s refluxed for 5 days, hydrolysed with water

~nd the ether layer w~.s decanted wd dried. Evaporation of the sol vent gave '.1 crystalline mass which rr8.S recryst2J. li sed :rom eth'lnol (6.5 g, 485.·), m.p. 233°. The compound was

·.r 0 cuum sublimed f'.t 160-180° /0.4 mm for ['11alysis.

Found: C,67.9; H,J.9; N,4.7f Parent ion 317

C~lc.for c18H12NAs: C,68.2; H,J.8; N,4.4;,"{. Parent ion 317. The infrared spectru.rri showed no !\"I{ stretch.

/\J'l~X (E) 218 (30,100). - lU~ -

.P.:30,rsatr.vrtycene oxide (1rn·,r;

Azars8.tryptycene ( O. 2 gJ was boiled. with nitric acid

( 1 5~1, 3 ml I for 45 min. The solution r12.s cooled and the oxide was filtered and dried (0.2 g, 95~~), m.p. (aqueous ethanol) 284-285°.

Found: C, 64.9%; H, 3-9%; N, 4.1%.

C8.l c. for c18H 12NAsO: C, 64. 9%; H, 3. 6%; N, 4. 2%­ Parent ion 333 (Cale. 333).

Reaction of azarsatryptycene with bromine

Azarsatryptycene (0.2 g) in dry chloroform (3 ml) was treated with a slight excess of bromine in chloroform. A small amount of c1n orange crystalline subst2,nce separated on cooling and was completely precipitated on the addition of dry ether (:', mlJ. The compound was filtered an:l washed with dry ether (O.] gJ. m.p. At .£Q.· 180° the ore.n.:;e colour disappeared and the residue remaining had m.p. 233° (T.L.C. identical to azCU"satryptyceneJ. Bromine analysis (as A13Br). Found: 42.8%

Cnlc. for c18H12NAsBr 3: 43.1%. The compound rr:-s decolourised on the addition of et h,.,nolic pot-...ssiun hydroxide and the re sul tin-• solution, on dilution with water, 2ave azarsatryptJcene oxide, m. p.

280-28:, 0 • !11ixed m.p. with S'<.mple prepared by nitric acid oxid,,tion of azars:itryptycene 0ave no de~-iression. - 110 -

A similg,r result ;·:as obse:r-ved when 2. s8l1lple of the bromine conq1ound ·,v:l s treP..ted with aqueous ethanol.

Attempted quate:r-nis'3tion of azarsatry1)tycene with silve:r­ fluorobor~te-methyl iodide

Azars'.l.tryptycene (0. 3 gJ was added to silver fluoro­ bo:r-ate ( 0 .1. 0 gJ in dry 1, 2-dichloroet~ ne ond methyl iodide

("< ml) W2.S added. Tl1e mixture was stirred for 15 min. and

2.llowed to stand overnijlt. The precipitate was filtered o.nd digested rri th eth.s.nol. Evaporation of the solvent left

!1 0 organic m2"terinl. The original 1, 2-dichloroethane filtrate r::-: s evapor2ted nnd the residue was recryste1lised from cthrinol, m.p., mixed m.p. and T.L.C. were identicql to

'.'. :--.QI' satryptycene.

Startins m'3terinl wqs also recovered when azars11.trypty­ ccne •.vro s boiled rri th methyl iodide for 20 hr. or allowed to

:1t 0 nd :1.t room temper,.,ture with a 5 mole excess of triethyl­ oxoniu1r1 fluorob orate in die hl oromet h...':..ne for 2 doys.

·,'lhen the com~·,ound w:1_s he8ted at 180° Hi t::i 2.n excess of

(0.2 G, 2 mole; - 1 11 -

d.2.· i ed.

~~: r;ln?nt. 0.7 r; (2'5;·; of r, colourless ·:i.rrn rr 0 s eluted

refluxed 1·1itb ~- 1,-,X'E':e e:ccess of mett1"'.nol-w2shed RMey nickel

-for 2 hr. T1w TTlixture ,·,~'.s cooled, filtered n.nd tho sol vent

,··'.:1 1:v8por-:-1ted. T:1e resichi_e w2,s chron,1 tographed by prep- o..r:..,tivc T.L.C. 11.:oin··s bensene-petrol ( 1: 1) as elucnt.

··:r.c1 infl'C>red T1 rorertie::; \'!ere identic8.l Pith 2.n :Juthen"':;i.c - 112 -

1J-STJ"B3TI'.::1U1ED-5, 10-DIHYDR0PH:2:TOi:'!IO SPHA znrns

~1 In 1890 it W'.l8 re;)orted I that diplrnn,yln.nine and

1hnsrhorus trichloride reacted 8t 250° in a se~led tube in

G 11e nresence of zinc chloride to give, on h,vdrolysis, a

,t~hle heterocycle of com,)osi tion c12H 10:NPO in low yield.

2he structu::'.'e of the product V/8,S sugcested 88 c:cr) or ©J:)QJH ru-Ph I ~ OH OH

(XCI)

The re?.ction w·~ s reinvestigated by Sergeev and

·(uury't'3hov, 72 ·:rho shor.red th,:,t tre NH ~roup was present and

~rn;:,~e 3te d th '1 t ( XGI J ·:ms the correct st:-ncture. They al so

:Jho1•1,?d thot zinc chloride vras unnecess2.ry for the condens­

"tion ~nd thnt the S"ffie rroduct W8S obt~ined ~hen fo~ ~ix ~ou~s. They obt~inert the phos,hinic ~cid (XGIII) - 1n -

"b.Y aerio.,l oxic18.tio!l of (XCIJ in tetr:_-,lir.. Gt 200°, and cJaimed to ~r8pr>.re the 10-chloro com;>ound C.::CIVJ by t:r-eg_tme of (X~IJ with thionyl chloride. The latter reaction does not seem to h~ve been repeated by later ·.vorkers (no reactic wo,s obtained when the reaction was attempted in this laboratory J.

(XCIIIJ (XCIV)

Haring73 subsequently investigated (XCI) in detail and ,repared a number of derivatives. On the basis of infrared evidence he su_

(XCV)

No 10-mlb sti tute d-5, 10-dihydropheno,hosphgzine s have been !'eported. Jo!'lc~s :-no T,hnn74 ;,repared. 2,2'-dibromo- - 114 -

,}irhenylamine (X:C'!III) by s'. Chqpman !'e~l.'ro_YlL-::ement of 2-bromo2heY1yl-H-2-b!'omophenyl benzimidoate (xc·n:) .

( XCVI) ( XCVII) (XCVIII)

'.'Then (XC'IIII) ,,,3,::3 tre8ted with butyl lithium a dili thio deri v,1 ti ve was obtained. However when phenyldichloropho sphine

·_-,., ~~ .·H3 df?d to the dil i thi o derivative an intractable polymeric

::1-:1teri ,.,,l vr'J.s obt -:1inrJd. Jones and M1:m.n sug,:::e sted that the presence of the s~conr10ry 8mine group was responsible for the fnilure of the re2-ction, as it allowed the possibility of extensive polymerisation when the ?.JTiine was treated with butyl lithium followed by phenyldichlorophosphine. They c ommP,nted that the reactio!'l may not have failed if a suitable rrotecting grou:;-:i for the amine was available. This su:;~estion later received confirmation when Baum et ~1. 75 rr2pnred n-2.lkyl-2,2'-dibromocliphenylamine by the r0nction of (XCVIII) with sodium hydride in the presence of

"TI ~1 kyJ iodide. When the N-alkyl :::unine rr.:J.s treated with hnt.vl lithium followed by phenyldichlorophosrhine, good

yields of 5,10-disubstituted-5,10-dihydrophenophosphazines - 115 -

·.·1i th N-methyldiphenylamine no reaction occurred. This behaviour reflects the similar results obtqin,3d when arsenic trichloride was reacted with N-methyldiphenylamine3 and supports the view5 th~t the first step in these cyclisation reactions involves the formation of an I.1-N bond to give a compound such as (XCIXJ which either rearranges intra­ molecularly or reacts with another diphenyla.mine molecule.

(XCIX)

It was decided to investigate two new routes to 10-substituted-5,10-dihydrophenophosphazines. H8rin8 prep8.red the acid chloride of (XCIII) by reacting it with thionyl chloride. 73 Phosphinic acid chlorides react vii th Grignard reacents to give good yields of tertiary phosphine oxides. 76 It was proposed to prepare tertiary phosphine oxides of the phenophosphazine system nnd to subsequently reduce them to the tertiary phosphines usinr: a raa~ent such as trichlorosilane which has been shown to sive, in ~en3ral, excellent yields of phosphines from phosphine oxides.77

It ,·ms recently reported tflat the trimethylsilyl group - 116 -

was P, useful protecting group for o.min~s in organometallic syntheses. 78 It was shown to be stable to alkyl lithium reagents and could easily be removed at the end of the reaction by treatine the product with methanol. It was hoped to reinvestigate the route of Jones and Mann to 10-substituted-5,10-dihydrophenophosphazines by first preparing N-trimethylsilyl-2, 2' -dibromodiphenylamine (CJ and then reacting this derivative with butyl lithium followed by phenyldichlorophosphine.

(C) - 117 -

i.2 Results and Discussion 10-0xo-10-chloro-5,10-dihydrophenophosphazine (CI), prepared by Haring' s method, 73 Wf',S found to be almost completely insoluble in all common orgQnic solvents.

H ©J:;© O Cl

(CI) The acid chloride was reacted with ethylmagnesium bromide in ether in a heterogeneous reaction. Even after sixteen hours reflux, a considerable amount of insoluble material was present. The ethyl phosphine oxide (CII) was isolated in 25% yield. The low yield is almost certainly due to the heteroc;eneous nature of the reaction and may have been improved if a higher boilinc solvent such as tetrahydrofuran or o-xylene had been used.

(CIIJ - 118 -

The oxide ( CII) •:,as also insoluble in most organic solvents and in this respect resembled the secondary

phosphine oxide (XCVJ. It was insoluble in ether, benzene

and acetonitrile ftlld it seemed that the trichlorosilane re duct ion would be impractical be C['_use of these solubility

ch8racteristics and hence this route to 10-substi tuted- 5, 10-dihydrophenophosphazines was not pursued. When diphenylamine was treated with butyl lithium followed by trimethylchlorosilane, N-trimethylsilyldiphenyl­ amine (CIII) was obtained in 61% yield.

fiMe 3 N / Ph ' Ph

(CIII)

However, all attempts to protect the NH group of

2,2'-dibromodiphenylemine (XCVIII) vd.th a trimethylsilyl group met with failure. When butyl li thi um-trimethylchlorosil ane was used, a white solid which could not be distilled was left when the solvent wns evapornted. In view of later results it is

1 i kely th~.t this solid was the N-li thio compound.

''/hen .-:i threefold excess of bis(trimethylsilyl)acetamide ( CIV), ~ rowerful silyl?ting agent, 79 w~_s he2.ted at 80° with ( XCVIII) in 2cetoni trile for sixt~en hours, only - 11? -

stnrti nc r1nt eri ~l W:-ls recovered.

( CIV)

It seems from these results that the llli group in (XC7IIIJ is too sterically crowded by the ortho bromo atoms to permit ingress of the trimethylsilyl group. It is surprisint; tlrn. t no reaction at all occurred with bis( trimethyl silyl) acetamide since this rea:::;ent has been successfully used to silylate the highly hindered 2, 6-di-t-butyll)henol in quantitative yield where other r ea·;ent s ~ave only poor yields. 79 Gilm2.n fonnd th'?t diph8nylamine could be converted to ?-lithiodirhenylomine by reaction nith butyl lithium. 80

The yield however was only 15%- It vras thought that a more r,ov1erful bn.se, sue h as the butyl li thium-tetramethylethyl- 0nediri.r1ine complex, 18 night convert diphenylamine to the 2,2'-dilithio deriv,..,tive and make it possible to circumvent the flrobler1 of the Jrotection of ( ::cvIII) by using ( CIII)

.,'hen ( CIII; 1:::-- :J tre8t

Thi s ,., Ci a i C De', t Ori r 1 ',','as n O t ch<:X'.'_ctcriscd ,.,_2 the yield obt2.in?C. r.:rJ,o this route to the

10-'Jub sti tu te:d-5, 10-dihyc1rophenopho 211h:::.c:i 112 s seem

One f 1_1:_•th8r re.-;cticn rras 0 ttemptod.. Alkyl lithium l'cn_:;ents h:::'1e hocrn shcwm to react ,;ith aJn:iue s to give, in

P:<.· ~;'JP., 1T, ·~-h::'c~hyJ-Jcetr•_lide ,:,ith n b1J_tyl ] ithiwa .:_;'.)V(? r,

--:"~' .'.·::i~lr:l of 11-:--~· :-"'---,·c.~ 1 Th0 u:.;chc>nism prt,1:10~-;cd for

OLi '.::R"li I p I 1\"U ~-~-irI:t' ) :2-C-N-R' RCR" + .I.I. J..\112 II I I II r\ \) R"l ::i 0

ond did not

trc~ted with 1.5 moles 8f

(CVI1 - 121 -

with the excess butyl li thi u:-:i to ~~i ve ( CVI) . Thus i r. te rmer3i =1.-te ( l]V; r.ru. st, with ~r, 17-di ~1h en~rl be nzarni des, col] ~tpse to t'.1e dir:henyl8mide ion E1.nd tl:.e ketone prior to hydroly:,L::, 2nc1 hence the amide '3rou;:i •:,as not suit2.ble for the ::.,rotectio:1 of the NH group in (X8VIII).

2, 2 '-Di bromodipl1enyl2r:tine ben?:cinice (XC7II) was treated

1'.'itb butyl 1ithiun followed by phenyldichlorophosphine

(Jespite the c1dverse results obtained rrith the diphen;ylamine b onzr~mic1e ree.,ction, in the hope that sone ( CVII) might be oble to be isol~ted even if only in low yield.

( CVII)

.,,.., C, A com11l2x ri1iztlu·e of rroduct s \ 'u....., ootci.il!ed on workup.

The l~•''"t rolnr fr~!Ction (by T.L.C. in

;r·?::-•?nt r:t 65.47. The -::lirh~tic protons comprised n larce - 122 -

cnvelo1,e 1t 6C.7-1.,3 8,!1d a six-line r:rultiplet w:1s visible

0n the low field cd:_;e of this rmiltiplet centred at 62.05,

9ugge,3tin_:; the presence of a CH 2-P '.;roup. It wa,s concluded th~t the ~ixture prob9bly consisted of phenyldibutylphosphine r=rnd r,n 3.ronati.c e:,mine which may h8,VG be:m the desired h0terocycle (c,nr). The yield of thi3 F1.ixture 'Nas so low ho·:,ever ( < 5~') o,s to m2ke separation of the two compounds seen of little value. - 123 -

") ") - . _) .2xperir.riental

10-Ethyl-5,10-dihydrophenophosphazine oxide (CII)

A 2uspension of 10-oxo-10-chloro-5,10-dihydropheno­ phosph0zine73 (1.5 g) in 1,2-dimethoxyeth~ne (50 ml) was

0 dde d to ethylr12.gne sium iodide ( 4. 3 g) in ether ( 40 ml) . The mixture ,,,r;_s stirred and refluxed for 16 hr., was cooled r, nd h 'ldrol,1'' sed with 2 one ous ammonium chlo:·ide solution. V • The product ·:,as extrrtcted with cr.loroforrn ( 300 m1) and the chloroform extract vras washed with w2.ter, dried and evapor­

~ ted. The residue (0.8 gJ was recrystallised from chloroform (0.36 g, 25%), m.p. 248°. The compound was insoluble in ether, benzene or acetoni trile.

Found: Parent 243.0826

Cqlc. for c14H14NPO: P?rent 243.0813.

~(a6 l11SO ,:it 100°J 9.91 (1H, s., NH); 7.35 (8H, mult., ArH);

1 .09 (2H, ~nnlt., CH 2J; 0.80 (3H, doublet of triplets JPH 19 Hz J!-IH 7.5 Hz, CH~).

"'max(£) 218 (24,600), 242 (shoulder) (7,800), 275 (16,800), ~10 (10,000;, ?47 (shoulder) (6,100).

!J-Trim•?thyl :;iJ yl di phenyl8Jiline ( CII I)

n Butyl lithinr:1 in petrol (18.5 ml, 1.6MJ was added to diphcnyl-,r.iine (5 .:;, 1 mole) in dry ether (30 mlJ and the - 124 - solution was stirred for 0.75 hr. Trimethylchlorosilane

( 3. 1 g; •112,s e.dded and the solution was stirred for 3 hr. The solution was filtered through celite, evaporated and the residu~l oil vacuum distilled to cive a pale yellow oil. b-P·o.8 112-114° (4.3 g, 61%).

S(CDC1 3) 7.08 (10H, mult., ArH); 0.23 (9H, s., SiMe 3).

Attempted preparation of N-trimethylsilyl-2,2'-dibromo­ diphenylamine. A. With n butyl li thiurn-trimetb,ylchlorosilane n Butyl lithium in petrol (4.7 ml, 1.6M) was added to

2,2'-dibromodiphenylarnine74 (2.5 g, 1 mole) in ether (25 ml). The solution was stirred for O. 5 hr., trirnethylchlorosilane

(0.86 gJ added and the solution was stirred for 3 hr. The solution was evaporated and the residue vacuum distilled. When all the sol vent was removed, the residue solidified.

Only 2-3 drops of a colourless oil distilled, b.p.0 _9 136°. The bath temperRture wns increased to 250° and no liquid. distilled. The pot residue was a black solid.

B. 'tYith bis(trimeth.ylsilyl)acetamide 2,2'-Dibromodiphenylamine (3 g) and bis(trimethylsilyl)­ Rcetamide (5.7 g, 3 roole) in dry acetonitrile (15 ml) were warmed at 80° for 16 hr. The solvent was removed and the residue was vetcuum distil led. A small amount of monosilyl­ qcetqmidc snblimed nt a bath temper?ture of 50°. The bulk - 125 - of the material distilled at b.p. 0 _2 122-132° (2 g). M.p., mixed m.p. and infrared spectrum were identical with the

starting amine.

Lithiation of N-trimethylsilyldiphe~ylrunine

The silyl deri va ti ve ( 1 g) in ether ( 25 ml) was stirred with N,N,N',H'-tetramethylethylenediamine (2.9 g, 3 mole) and n butyl 1 i thium in petrol ( 15. 6 ml, 1. @11, 3 mole) for

2 hr. The product was poured onto dry ice o.nd methanol

( 20 ml J was added. The solution wo.s warmed at 80° for 1 hr., acidified and extra.cted with aqueous sodium bicarbonate solution. The bicarbonate extract was acidified, extracted with ether, dried and evaporated to give 0.3 g of acidic mi::iterial vrhich was recrystallised from aqueous ethanol ( 0 • 1 2 g, ca. 1Of) , m• p . 1 8 3° .

Reaction of n butyl lithium with N,N-diphenylbenzamide n Butyl lithium in petrol ( 17 ml, 1. 6T1lj was added to a

suspension of N,:T-diphenylbenzamide (5 g, 0.66 mole) in dry

ether ( 100 ml). The mixture was re fluxed for 4 hr., and hydrolysed ·ai th w::iter. A small a.mount of r1hi te solid

separated and w2s filtered ( 1.4 gJ and shown to be identical with the startinz benzamide. The filtrate was washed with water and the ether layer was dried and evaporated to give

n bro•.·m oil ( 4. 2 [!,J which was chr omc..togrci.:phed on alumina - 126 -

( 160 z; usin_::; petrol-bem~ene (4: 1J 8-S eluent. 2.2 g of

di::>henylamin:: ( 100%, based on :- . 6 ,: of ben~8.mide consumed)

,.,,,., 2 clu ted. The elue nt was ch--? n,32 cl to bcn7,ene 2J1d 1. 2 g

(41;') of di-(n butyl)phenylcarbinol nas eluted. N.M.R.,

infrn.red ri.nd T.L.C. ,.,,ere identic8l with an authentic sample

obtain?d as described below.

Di-(n butyl)phenylco..rbinol

nonan-5-one ( 3 g1 in ether ( 20 ml) was added to phenyl lit!lium in ether (30 ml, 1.1M, 1.7 mole) and the mixture wn.s stirred for 2 hr. The solution v,as hydrolysed with

W'1 ter, the ether loyer was de canted, dried and evaporated.

The residual oil W8.s vacuum distilled, b. p. 0. 8 107° ( 3. 2 g, ,, 83 O o 6) C1; J 1 it • b. p. 1 1 2 -12 2 .

Attemptecl preparation of 10-phenyl-5 2 10-dihydrophenophos­

phazine (CVII) vin 2 1 2'-dibromodiphenylamine benzamide

A suspension of the benz::unide ( 3 (!,J in ether (50 ml)

W8.S stirred with N,N,N',rT'-tetramethylethylenediamine (3.2 g, 4 r.1ole) '1nd n butyl lithium in petrol (16.8 ml, 1.6M, 4 mole)

for 1C1 min. Phenyldichlorophosphine (1.24 g, 1 mole) in

ether ( ?O ml) ··.r?.G ::dded and the mixture vrn s refluxed for

1 hr. The mixture ',?:=ts hydrolysed ·;1i th ·:1.0.tcr and the ether

1 ~yer ·::n.s de c~•ntc d, clrie d 3.nd evnpornte d 0 nd the residual - 127 -

b~nzene-chloroformJ '-'IRS collected (0.22 f!,). T.L.C. in benzene-petrol (J:7) shov,ied the.t this fraction consisted of two compounds.

c5 ( C"!)C 1 3 ) of the mixture : 7 • 7 - 5 • 8 ( 100 sq. , bro ad mu 1 t • , ArH); 5.47 (4 sq_., broR.d s., NH); 2.05 (10 sq., 6 line mult., CH 2P); 1.8-0.7 (60 sq., broad J:IUlt., aliphatics). Further elution of the column gave e, mixture of products. - 128 -

SECTION 4

TH:8 WITI'IG REACTION WITH

HET2ROCYCLIC PH08PII"1IUUI:I SALTS

4.1 Introduction

The Wi ttir~ olefin synthesis, in ':rhi ch a phosphonium s~lt is treated vrith a b8se and then with a carbonyl compound, to ~ive an olefin (Reaction 1), is one of the most widely used m•2thods for preparin:-: olefins. 84

+ base +- R"R"' CO R 3PcH 2R•x- --➔) R1 PCIIR' > R~PO + R'CH = CR"R"' -' Re:1ction 1

A l8r,<3e number of phosphonium salts h3,Ve been used to prepA.re the intermJdi['_te yli ds. The reaction has been externled so that :-> number of other cl2,sses of phosphorus compoun~s, includin1 phosphonate esters, 85 phosphor8m1dntes, 86 ~na phosphine oxides 87 have been used in 1. ;)i tti!;-tyrie olefin synthesis.

?,:''I stud.i? s h-:vc h2 ?n re:r;:orted of the use of hetero-

o,q on 'h~ "1A o:cide:3i '. - bnt ri WittL:-tYL'-~ react;:in is !Wt - 1 20 -

Bose l R-CHO

(C'lIII)

Bose ) R'CHO

~hen used in a Witt!~

Tf )/'(~ ve r, O ?1 the "rld it ion of bn :-;P,, ( c;n unr1erwent :-in e limin­

') t; J!'l r,,-.e~io1, t'_) ~:i'.'•"' " :ho3phine (C~:I) . 90

Bose ) Ph

( 0 .'TI \ J ..... ~'- • hy ~h8 re2ction o~ tr8ns ~Ar~nyl2cet~ne 7ith the bis ylid i'rorn hu t·rne-1, 4-1-Ji 2tri pht~~ho sphonium di bromide. 91

:iowever onl:,' s?:rrrn.etrical di2nes c9.n. be prepo.red by this route.

Compounds such ns 1,1-diphenylphosphorinanium bromide

( C~GI) coulc1 ':ive an uns8turated phosp11ine oxide if used in n '.'Ti ttig re8cti-:m, !'nd the resul tin,c; unsaturated phosphine oxide co1..1.lJ unde-!'.'co 8 fu.rther Wi tti~;-tY1Je reaction to give n die ne, "l.S :Ln Sc lh~me 1.

GJ>P, Ph Ph

( CXII;

Scheme 1

If tf~is sequence was practicable, then it should be possible to ~rcp~re un~~unetrical dienes, ~nd by alkylqtion

be synthesised. In theory at Jeri.st, it should be possible t:J C"r1..·y out ::-inch '.' rnul ti step re:1ction in the one reP~ti.on - 1: 1 -

h0t0r0cyclic J~lts were readily ~ccesJiblc. The five, by !,:8-rkl by the r,~r,ction of the appropri2te a., w dihnlide ~ith tetr~~h8nyldiphosphine. 92

H2> ( 2 Ph2PCl ...... L..__i -> Ph2PP Ph2 Brn8c> + +Ph2PBr /p\ Br Ph Ph CCXIII> n=S, 6, 7.

The scheme mc1,y '.:1.lso have provided a route to squalene which used more readily available sta:rtinc materials then th0se used in previous syntheses, as shown in the following serinence. - 1: 2 -

\:>BasetMel

i)Base ii)Q.5 mole

Alkyl:1.tion with hr-ilides other than methyl would provide unnatural squ!'tlenes which would be of considerable biologicql interest.

Scheme 1 1:1ns hence investigated as a potential high yield route to a,W dicnes. - 133 -

4. 2 Results Gnd Discussion

The five- and six-membered rinc s2,l ts ( CiCIII, n =

5, 6) were prepr-tred by a modification of l.Iarkl' s 92 method.

It wris found unnecessary to isolate the intermediate tetraphonyldirihosphine in this reaction .-:;,nd a slight improvement in the yield resulted. The perchlorates of these S."'llts were used in our study as the bromides were found to be deliquescent. Sodium dimsyl ( cxrva), the compound formed by the ':\.Ct ion of sodium hydride on dimethyl sulphoxi de, has been sugGested as a powerful base, superior to organolithium reagents, for Wittig reactions. 93

CH 3 - S - CH 2 Na+ ,1 0 (CXIVa)

However, when sodium dimByl was rencted with

1,1-diph~nyJphosphorinanium perchlorate (CXII) and benznldehyde ndded, n mixture of phosphine oxides was formPd ... na ~7.r.T .R. indic3ted only a snu-

-:it 56. 27. The m8jor product was isol2ted by chromatography nnd wqs sho'7n to be 1-phenylphosp!1orin?cn oxide (CXIVJ, the known s2..ponific..,tion product of the heterocyclic salt (('YIIJ q4 \ V _. Ir,. • - 134 -

0 /~ Ph 0

( CXIV J

Evidently there were traces of water or sodium hydroxide present in the sodium dimeyl rea~ent; even when fre sh1y di st illcd ( ex CGlcium hydride) dimethyl sulphoxide w~s used, (CXIV) was the major product.

Vfhen phenyl lithium in ether was used as the base and the resultint; ylid was treated with benzaldehyde and warmed for trio hours, the alkene phosphine oxide (CXV) was isol~ted in 56% yield.

~Ph

( CXVJ

'.'fhen the r2"J_ction ·.·ms worked up after stirring at 20° for O. 75 hr., 2, sm::-.11 amount of a phos1)honium salt was isoln.ted which v.1ns identified as (CXVI).

( CXVI J - 135 -

The salt exhibited 9n OH stretchin~ b~nd in the infrared at 3410 cm- 1 and the N.i·-I.R. s~;ectrum showed a quartet at 6 4. 90, integrating for one proton and corres­ ponding to the benzylic hydrogen. The N.M.R. spectrum integrated for (CXVI) and microanalysis of the picrate confirmed the structure. Isolation of such p hydroxyphosphonium salts from 'Ni ttig reactions occurs if the intermedi2.te betaine is relatively st~ble. The presence of substituents which decrease the positive charge on phosphorus, can lead to betR ines which are relatively stable, since they decrease the driving force for betaine decomposition. Thus the~ hydroxyphosphonium salt (CXVII) has been isolated in the reaction of tri-(o-methoxyphenyl)methylphosphonium iodide with benza1dehyde. 95 In this case the electron-donating o-methoxyphenyl groups decrease the positive charge on phosphorus and hence decrease the driving force for betaine (CXVIII) decomposition.

OMe OMe

( CXVII) ( CJCVIII) - 1:,6 -

Electronic facto~s would not seem to be responsible for the st~bility of the betaine fron the heterocyclic s11.l t ( CXII) and stereo chemical factors were considered. Models of the betaine, however, did not indicate any obvious stereochemical factors to account for its stability When (CXVI; was warmed with sodium hydride in 1,2-dimethoxyethane, T.L.C. indicated quantitative conver­ sion to a product of identical Rf to (CXV). When the five-membered ring salt (C.LIXJ was treated \'ti th phenyl li thiun followed by benztldehyde and the product was warmed for two hours, (CX:X:) was isolated in 67% yield.

C - CPh w/pp l04 Ph h / vJ Ph Ph (CXIX) (CXX) These results indicated that the first step of the proposed diene synthesis proceeded in reasonable yield with phenyl lithiu:r.1 as the base. Phosphine oxides such as (CXV; 8nd (CXX) would form non-stabilised carbanions when an a proton was abstracted. The next step of the proposed diene synthesis, namely the formation of the carbanion of

An nlkyl phosphine oxide and its subsequent alkylation or re:::i.ctiol'! with a carbonyl compound, was investigated using - n7 - ethyldiphenylphosphine oxide as a Model compound, since it would also form a non-stabilised carbanion on met:::.llation. Unless the a proton is particularly labile, as for example in benzyldi:Jhenylphosphine oxide, visorous conditions have generally been used to obtain the inter­ medi?.te carbanion from phosphine oxides. 87 Reagents such as l)Ot:1ssium tert-butoxide or sodarnide, in refluxing benzene or toluene, have been used. Decomposition of the carbonyl co~pound-phosphine oxide adduct also requires vi~orous conditions. Consequently the use of phosphine oxides in a Wi tti[s-type syn the sis has not been widely applied, since other substrates, rei;uiring less vigorous conditions, have been available. A number of experiments were carried out in an Qttempt to metallate ethyldiphenylphosphine oxide in hish yield. The reaction was followed by the addition of methyl iodide to the metallation mixture and subsequent analysis of the products by N.M.R. Bases used in the metgllation e:rperiments included sodium dime_yl o.t room temperature, sodium hydride in N, N-dimethylform'.:'JTI.ide-methyl iodide at 60°, phenyl lithium at ro:::>m temrier ::i.ture nnd n butyl lithium 8.t room temper ?tur e In ~11 these cnses, no alkylation of the phosphine oxide - 1_"'8 - was observed. With e_n excess of phenyl li t::.ium at -70°, a 75~ recovery of a mixture of phosphine oxides was obtaine?d am 11.l~.R. of the mixture indicated 60;; alkylation

The hi~hest yield vras obtained when one mole of n butyl li thium-N, l;, N', N' -tetra."!1.ethylethylenediamine complex at -70° was used; a 71~ recovery of a mixture of phosphine oxides w2s obtained and N.I.:.R. indicated 90% n.lkylation. ThG 1: 1 adduct formed betrreen butyl lithium

'ind the dici_mine h2~s b2en shown to be ? very powerful metsllating agent 18 and appears to be of promising value in this study. Ho'.'lever, for the proposed diene synthesis to be 2. :practicPble method, it woald be necessary to obtain virtu.~lly 100f r:wt1-ll2_tion in •3ach step if the reaction w·,s to be used ns envisa0ed - a nml tistep process in the one reaction vessel.

When (CXII) •72,s treated ·.vith n butyl lithium in nimethy1 sulrihoxide followed by methyl iodide, a. 63)~ yield of n mixture of phosphonium salts nas isol~_ted. N.M.R. injic,,ted th.,_t -:;he mixture cont•~jnod So:· c_ methyl salt ~na 20~ (CXII). ~hen this crude a methyl heterocyclic

:~"lt 1:-r'ls tre-._.tcd ,-rith on2 mole of butyl lithium follor.•ed

-·rour ..\ -1:1·~1:t 8t h1.79 corre:__,~)01v1cd to:-:_ m0thy] your - po -

(CXXII)

~as obtained i~ the

since tr.:e ylid lc?.l1inc3 to (CX::I)

At thin stn.:c, ~ork on this proj2ct ~as suspended ·. ir:c'2 t!lr: rosul ts obtclin2d ,:,ere not suffic:i<:!ntly Gncoure.g-

~rct, CO:'.lbin~d ·,,it'.1 th2 dis::1,vpointin~--: 1'0'.JUlts from tho 1 • 141 2. 141 Sodiun dims.1,rl 0~1 1, 1-diphe:r:yl'-:.-,ho::-;~·-ihorinaniun 142 r,?l'r:!U or·1tr.:. I--:Cll·,tiCJn of 1-i,h0nylphosphorir.2.n ozid0 ( c-:Gv).

4 . 142 144 I :::orro11yl di ~>h en_ylpho sphine oxide fr01:i 144 e th.1,rl ,_l i ;J/1,:: :r1yl ·1)ho s1)hi ne oxide.

7 . 1, 1-Di 1~hen;,rl-2-m.::thylpho sphorin':·.nh1r1 145 perchlo::'..':".te ~na its reaction Fi th. butyl Jithiu1.1-b2nsc.ilc1chyde. - 141 -

1,1-Dipben,ylphosphorinanium percblorate Cblorodiphenylphospbine (97.8 g) in ch-y T.H.r. (80 ml) was added dropwise to a suspension of lithiu:na (3.3 g) in T.H.r. (220 ml). The mixture was refiwced for 4 hr., cooled and filte~ed under nitrogen. o-Dichlorobenzena (300 Ill) was added to the solution and the T.H.P. was removed by distillation. 1,5-Dibrouopentane (60 g) was added to tbe solution which was then added ch-opwise to refluxing o-dicblorobenzene (100 ml). The :mixture was refluxed for 20 min. and allowed to stand at room temper­ ature overnight. Tbe salt was filtered and recrystallised from metbanol-etb.er, m.p. 259° lit.92 261-262°, 48.5 g (84% based on an expected tetraphenyldiphosphine yield of 100%). Tbe bromide was converted to the perchlorate by metatbeeis with aqueous methanolic sodiWD perchlorate solution, m.p. (aqueous methanol) 208°. Pound: c, 57.3%; H, 5-9%­ Calo. for c1.,a20PC104: C, 57.5%; H, 5.6%. o(CP 3C00H) 7.81 (10H, mu.lt., ArH); 3.00 (4H, mult., a CH 2); 2.33 (2H, Dllll.t., Y CH 2); 1.95 (4H, ml.t., ~ CH 2).

11 1-Dipben.ylpboapholanium perchlorate Tbie aal t was prepared in an analogous manner in 71% yield (based on tetraphenyldiphoaphine), m.p. 114° lit.92 114-1150. - 142 - b (CDC1 3) 7.70 (10H, mul.1., ArH); 2.97 (4H, llllt., a CH 2); 2.25 (4H, lllllt., ~ CH 2).

A11empted preparation of 1-pheDYl-6-dipheylphoaphiDYlhex-

1-ene via sodium 41•Vl on 11 1-dipbeDYlphoephorinanium perchlorate 1,1-D1phe117lphoephorinanium perchlorate (4 g) in dl'7 dimetby'l su.lphoxide ( 15 ml) was added to a fleeshl7 prepared solution of aodium dime7l ( 1.13 g, 1 mole). The deep orangt solution was stirred for 10 min. and benzaldeh7de (1.37 g) added. The mixture was warmed at 50° for 0.5 hr., waa cooled and poured into wa1er ( 200 ml). The solution was extracted with chloroform and the chloroform extract washed with water and dried. EYaporation of the solvent gave an oil (2.5 g). R.M.R. (CDC13) of 1he crude oil showed: b7.56 (22 sq., ArH); 6.27 (0.5 aq., mul.t., olefinic); 1.94 (30 aq., IIDll.t., aliphatic). Preparative f.L.C. on a 200 mg sample using ethyl acetate as eluent gave 140 mg of a crystalline phosphine oxide, ••P• 127° identical in every reapect with 1-pbenylpboephorinan oxide.94 lo other crystalline coapeund could be isolated.

1-Pbegl-6-dipben;,lphoephin,rlbex-1-ene (CXV) via pben,rl

lithium on 11 1-dipheulphoaphorinanium perchlorate 1,1-Dipbenylpbosphorinanium perchlorate (5 g) was adde~ to a solution of phenyl lithium in ether (15 ml, 1M, 1 mole) !be eolu11on wae stirred for 10 min. and bensaldeb7de - 143 -

(1.5 g) in 1,2-d1aetboxye1bane (20 ml) added. !be aolution wae war11ed at 70° tor 2 br., poUl'ed into water and extracted with benzene. !be benzene en»ac1 waa waebed with water, dried and evaporated to give an oil (4.2 g) wbicb. wa• cbro11atograpbed on alumina ( 80 g) uaing benzene­ chloroform (1:1) as eluent. A brown oil (2.8 g, 56%) was eluted which slowly crystallised, ••P• {benzene-petrol) so•. Pound: C, 79.8%; H, 7.05%• Cale. tor c24a25PO: C, 80.0%; H, 6.9~. &(CDC1 3) 7.43 (15H, mult., ArH); 6.24 (2H, mu.lt., CH=CH); 2.21 {4H, Dllllt., PCH2 and CH2-0=C); 1.64 (4H, aut., CH2>· When the reaction llixture was stirred at room temperatlll'e tor 0.75 hr. after the benzaldehyde addition, and then worked up as before, an oil was obtained (5 g) which wa■ dissolved in acetone and tr11u:rated with benzene to give a crystalline B hydroxnboapbonium salt (CXVI) (0.3 g), ••P• (methanol-ether) 239°.

&(CP3COOH) 7.72 {15H, mult., ArH); 4.90 {1H, quarte1 JPH 9.5 Hz JHH 7 Hz, cg_oH); 2.16 {9H, very broad JDlllt., ali­ pha11os). Microanalyaia was performed on the picrate, ••P• 190° yellow needles. Pound: C, 61.2%: H, 4.5% Y(OB) 3410 __ ,

Cale. tor C20H28w3o8P: C, 61.1%; H, 4.8% • .l ••11 ••ple of the P bydroxn,bospbonium aal t waa war■ed at 50° with an excess of sodium hydride in - 144 -

1 , 2-dinletboxye1ibaDe tor 2 hr. under n1vogen and 1ihe produc1i waa hydrolysed w11ih water. !.L.C. (2% aa1ibanol in oblerotor■) ahowed a single spot ot identical Bt to the alkene pboapbille oxide.

1-Pheul-5-diphe:n;rlpbosphiylpent-1-ene (en) !hie waa prepared in 6~ yield in an analogoua manner to the phosphine oxide from the ■ ix-membered ring aa11i, uaing phenyl li1ih1Ulll-benzaldeh7de on 1 1 1-diphell,Jlphe ■pholaniua perchlerate, ••P• (benzene-petrol) 161°. Pound: C, 80.1%; H, 6.9%. Cale. tor c23H23PO: C, 79-75%; H, 6.~. b(CDC1 3) 7.44 (10H, llllllt., ArB); 6.28 (2H, m.11., CB•CH); 2.17 (6H, broad nmlt., alipha1iics).

Converaion ot etb.yldiphen,ylphoaphine oxide to iaeprop,:ldiphen.ylphoaphine oxide via but7l li1ihiWl-diaaine co■plex and ae1ib,Jl 1od14e n Butyl lithium in petrol (5.4 Ill., 1.611) waa added to a auapenaion ot ethyldiphe:nylphoaphine oxide ( 2 g, 1 mole) in ether (20 Ill) containing K,K,K 1 ,B•-teu-811leth7letbylene• diaaine (1 g, 1 mole) at -10•. !be Dlixtul'e waa stirred at -10• fer 2 hr. and ■ethyl iedide (2 ml) added and the teaper­ ature waa raiaed 1io 20•. !be mixture was poured into water and extracted with benzene. !he benzene extract was washed - 145 - witb water, dried and evaporated to give a white solid (2 g) wbicb was recryatalliaed from benzene-petrol, ••P• 138-142°. lit.96 142° (1.5 g, 71~). b ( CDC1 3) 7. 50 ( 26. 5 sq., mu.l:t., ArH); 2.38 (3 eq., mu.1 t., CH); 1.20 ( 13 • 7 sq. , quartet superi■po ae d on sextet, CH 3) • Estimated as 90% iaopropyl and 10~ ethyl compounds.

11 1-Diphevl-2-methflphosphorinanium perchlorate n Butyl lithium in petrol (8.8 ml, 1.6M) was added to 1,1-diphenylphoaphorinanium perchlorate (5 g, 1 mole) in dimethyl sulphoxide (15 ml). The aolQtion was stirred tor 10 min. and methyl iodide (3 ml) added. ~he solution was poured into water and extracted with chloroform. The chloro­ form extract waa washed with water, dried and evaporated. !he residue was dissolved in aqueoua methanol and aqueous sodium perchlorate was added. The mixture was stirred for 1 hr. and was diluted with water. !he salt was filtered and recrystallised from methanol-ether, m.p. 181-185° (3.3 g, 63"). b(CP3COOH) 7.80 (78 sq., mult., ArH); 2.90 (30 aq., Dm.lt., a protons); 2.06 (50 sq., lllllt., other ring protons); 1.43 ( 20 sq., quartet JPH 17 .9 Hz JHH 7.1 Hz, CH3). Eatimated aa 80" methylated salt. - 14f>e. -

Reaction of 11 1-diphen,rl-2-metbJ'lphosphorinaniwa perchlo~ate with butyl lithiUll-bensaldehYde n Bu.t7l lithiWll in petrol (16 ml, 0.5)() was added to crude 1,1-diphenyl-2-aeth7lphoephoriDaD1wa perchlorate (2 g, 1 mole) in diMtbyl sulphoxide ( 10 ml). !he solution was stirred for 10 min. and benzaldeh7de (0.6 g) added. !he solution was stirred at room temperature tor 1 hr. and was then heated at 60° for 1 hr. !he lliriure was poured into water, extracted with benzene and the benzene extract was washed with water, dried and evaporated. The reaidual oil ( 2.1 g) was ohromatograpbed on aluaina (80 g) using chloro­ form-benzene (7:3) as eluent. 1.7 g of a colourless oil was obtained. R. ■ .B. (CDC13) of the oil showed: b 7.39 (118 sq., JIUl.t., A.rH); 6.20 (9 sq., mu1t., CH=CH); 2.17 (32 sq., mult., C!!,P and CH 2-C=C); 1.79 (12 sq., a., CH3-C=C); 1.62 (25 sq., Dllll.t., CH 2); 1.18 (14 aq., quartet JPH 17 Hz JHH 7 Hz, CH3-C-P). Eatillated a■ a mixture of .£1.· 10% ( CXV) and 45% each of (CXXI) and (CXXII). - 146 -

Reterencee

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ACKNOWLEDGEMENTS

The author wishes to thank his superviaor, Dr. M.J. Galla.gb.er, tor man., helpful discussions and suggestions throughou"t the course of this work. The staffs of the N.M.R. units at this University­ and at the University of Sy-dney are thanked tor the K.M.R. spectra and the start ot the Mass Spectrometry unit at the University of Sy-dney is thanked tor the mass spectral data. Dr. E. Challen, of this Department, is thanked tor many of the microanalytical figures quoted in this thesie. The award of a Colllllonweal th Postgraduate Scholar­ ship is gratefully acknowledged. Pinally, the author would like to thank his parents tor their continued support, encouragement and patience during his years at the University.