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.