The alkylation of 8-hydroxy-6-methylthiopurine and the reactivity of 8-hydroxy-3-methyl-6-methylthiopurine

Abstract

In aprotic solvents, 6-alkylthio-8-hydroxypurines are alkylated in position 3. In 8-hydroxy-3-methyl-6-methylthiopurine (II) the alkylthio-group exhibits low reactivity; e.g., it undergoes thiohydrolysis only with difficulty. Treatment of (II) with chlorine causes oxidation to the methylsulphonyl derivative (IV), in which nucleophilic substitution at C-6 proceeds much more readily than in (II). However, replacement of the 8-hydroxy-group in (II) by chlorine to yield 8-chloro-3-methyl-6-methylthiopurine (VI), restores the reactivity of the 6-alkylthio-group. For example elemental chlorine converts (VI) into 6,8-dichloro-3-methylpurine (X). In the latter, the halogen in position 6 rapidly exchanges with nucleophilic reagents.