A concise and efficient synthesis of amino-substituted (1H-benzo[d]imidazol-1-yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of six examples.

A concise and efficient synthesis of a series of amino-substituted benzimidazole-pyrimidine hybrids has been developed, starting from the readily available N-(2-aminophenyl)-6-methoxy-5-nitrosopyrimidine-2,4-diamine. In each of N-benzyl-6-methoxy-4-(2-phenyl-1H-benzo[d]imidazol-1-yl)pyrimidine-2,5-diamine, CHNO, (I), 6-methoxy-N-(4-methoxybenzyl)-4-[2-(4-methoxyphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, CHNO, (III), 6-methoxy-N-(4-nitrobenzyl)-4-[2-(4-nitrophenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, CHNO, (IV), the molecules are linked into three-dimensional framework structures, using different combinations of N-H...N, N-H...O, C-H...O, C-H...N and C-H...π hydrogen bonds in each case. Oxidative cleavage of 6-methoxy-N-(4-methylbenzyl)-4-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, (II), with diiodine gave 6-methoxy-4-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, which crystallized as a monohydrate, CHNO·HO, (V), and reaction of (V) with trifluoroacetic acid gave two isomeric products, namely N-{5-amino-6-methoxy-6-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidin-2-yl}-2,2,2-trifluoroacetamide, which crystallized as an ethyl acetate monosolvate, CHFNO·CHO, (VI), and N-{2-amino-6-methoxy-4-[2-(4-methylphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidin-5-yl}-2,2,2-trifluoroacetamide, which crystallized as a methanol monosolvate, CHFNO·CHO, (VIIa). For each of (V), (VI) and (VIIa), the supramolecular assembly is two-dimensional, based on different combinations of O-H...N, N-H...O, N-H...N, C-H...O and C-H...π hydrogen bonds in each case. Comparisons are made with some related structures.