Unexpected reactions of 4-amino-2-methylsulfonyl-5-nitro-6-phenylethynylpyrimidine with nucleophiles

Abstract

Recently, we have reported that 4-amino-6-arylethynyl-5-nitropyrimidines in dry pyridine undergo smooth intramolecular cyclization to give pyrrolo[3,2-d]-pyrimidine 5-oxides [1,2]. The latter compounds, being aza-analogues of isatogens, attracted our attention as potential traps for free radicals in biological milieu [3][4][5]. In continuing our research aimed on the synthesis of polysubstituted pyrrolo-[3,2-d]pyrimidine 5-oxides via cyclization of 6-arylethynyl-5-nitropyrimidines, we decided to perform modification of the 2-position of the starting 6-arylethynyl-5-nitropyrimidines based on oxidation of methylthio moiety followed by nucleophilic substitution reaction. Thus, reaction of 4-amino-2-methylthio-5-nitro-6-phenylethynylpyrimidine (1) with excess of m-chloroperbenzoic acid in dihloromethane at room temperature provided the corresponding 4-amino-2-methylsulfonyl-5-nitro-6-phenylethynylpyrimidine (2) in 70% yield. Unfortunatelly, the reaction of compound 2 with some nucleophilic reagents did not lead to formation of 2-substituted 4-amino-5-nitro-6-phenylethynylpyrimidines 3. We observed that C≡C bond of the title compound appeared to be more reactive towards nucleophiles than the C(2)-SO 2 Me moiety of the pyrimidine ring.