Mechanistic studies of the interactions of hexamine and some derivatives with electrophiles

Abstract

Mechanistic studies of the nitration of hexamethylene- tetrajnine (1) and some derivatives are reported and are compared with acetylation reactions. Nitration reactions, with nitric acid, were carried out using mixtures of [(^15)N(_4)] - and [(^14)N(_4)] - compounds, and the destination of the nitrogen isotopes in the products was determined mass spectro- metrically. The results show that in nitration of (1) to give 3,7-dinitro-l,3,5,7-tetraazabicyclo[3.3.l]nonane (DPT) extensive ring cleavage occurs to give species containing amino-nitrogen fragments. However, the nitration of 3,7- diacetyl-1,3,5,7-tetraazabicyclo[3.3.1]nonane (DAFT) to 1,5- diacetyl-3,7-dinitro-1,3,5,7-tetraazabicyclo[3.3.1]- nonane (DADN) involves selective cleavage of the methylene bridge. Kinetic studies are reported of the pH-dependence of the decomposition of DPT in aqueous media. The results show that at all acidities two stages are observed. The first stage, k(_1), involves catalysis by protons and hydroxide ions, and it is suggested that reaction occurs via a low concentration, ring-opened structure which is in equilibrium with DPT. In acidic solution an intermediate is observed which is identified as nitramide (NH(_2)N0(_2)). Methylenedinitroamine is shown not to be an intermediate in the decomposition of DPT, since its rate of decomposition is too slow. Mechanistic studies were also carried out on the synthesis and decomposition of 3,7-dinitroso-1,3,5,7- tetraazabicyclo[3.3.1]nonane (DNPT). Experiments using mixtures of [(^15)N(_4)] - and [(^14)N(_4)]-compounds showed that relatively little isotopic mixing occurs during nitrosation of (1) to DNPT, and hence the predominant reaction involves cleavage of a methylene bridge with the ring structure remaining intact. Data obtained for the decomposition of DNPT in acid solutions suggested that the rate-determining step of this process involves C-N bond cleavage, and were consistent with the intermediate formation of nitrosamine (NH(_2)N0) .Kinetic studies were conducted on the decomposition of 3,7-bis(arylazo)-1,3,5,7-tetraazabicyclo[3.3.1] nonanes in acid solution to the corresponding aniline. Evidence was found for the formation of an intermediate methyleniminiumion, the UV/visible spectra of which could be observed in acetonitrile solutions containing only minute quantities of water. (^1)H NMR studies of solutions of hexamine in DMSO-d(_6) containing electrophilic species suggested that under these conditions quaternary salts of hexamine were formed, rather than cleavage of the molecule to form N-substituted six- and eight-membered ring species.