The syntheses of 1,4-dimethyl-5-azaindole and 4-chloro-1-methyl-5-azaindole were investigated, and undertaken starting from 1-methylpyrrole, and were obtained in overall yields of 32 and 16% respectively. Reactions, based on the known reactivity of the corresponding 2-substituted pyridines, were performed on both compounds in order to gain some insight into the reactivity of the 4-substituted-1-methyl-5-azaindoles. The only 4-substituted derivative of 1,4-dimethyl-5-azaindole obtained was 1-methyl-4-styryl-5-azaindole-which is probably the only example of a reaction involving a methyl group in the pyridine ring of an azaindole. 4-chloro-1-methyl-5-azaindole was aminated directly with ammonia, methylamine and dimethylamine and reacted with the phenoxide ion and organolithium-generated anions. Both 1,4-dimethyl- and 4-chloro-1-methyl-5-azaindole reacted with paraformaldehyde in acidic conditions to give the respective bis(4-substituted-1-methyl-5-azaindol-3-yl) methanes. This synthetic work produced some novel 4-substituted-1-methyl-5-azaindoles, and demonstrated the reduced reactivity, relative to the corresponding pyridine derivatives, as theoretically anticipated due to the combination of the electron rich pyrrole ring with deficient pyridine. All the azaindoles prepared were examined by 13C and 1H spectroscopy and the spectra fully assigned. Ultra-violet and mass spectra were obtained for many of the compounds, which were analysed, and the dissociation constants of some were also measured, showing the compounds to be generally of a basic nature.
|Date of Award||1983|