Physical properties and chemical reactivity of 8-(methylthio)hypoxanthines

Abstract

N-Methyl derivatives of 8-(methylthio)hypoxanthine(1) were synthesised by N-methylation of various 8-(methylthio)-compounds or by S-methylation of appropriate 8-mercaptopurin-6-ones. In 8-(methylthio)hypoxanthines, protonation takes place at the same positions as in the corresponding hypoxanthines. However, the neutral forms of compound (1), its 1- and 7-methyl derivatives and the 1,7-dimethyl homologue are methylated preferentially at N-3, in contrast with the alkylation of the corresponding hypoxanthines which takes place in the imidazole ring. This difference is ascribed to the steric effect of the 8-SMe substituent.

The chemical shift of the S-methyl group is influenced little by protonation of the molecule, unless mesomerism can involve the thioether group. Participation of sulphonium-like resonance forms is, however, strongly hindered in the 7,9-dimethyl derivatives of (1). The latter compounds also undergo ready demethylation, hydrolysis, and thiolysis of the 8-methylthio-group.