Synthesis of 4- and 5-disubstituted 1-benzylimidazoles,important precursors of purine analogs

(Z)-N-(2-amino-1,2-dicyanovinyl)-N'-benzylformamidine 6 has been prepared both from the reaction of benzylisonitrile with the hydrochloride salt of diaminomaleonitrile and from reaction of ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate with benzylamine. Based-catalyzed cyclization of amidine 6 led to imidazoles 7 and 8 depending on the reaction conditions. Compound 7 reacts with acetone and butane-2,3-dione to give the 2,2-disubstituted-6-carbamoyl-1,2-dihydropurines 9a and 9b respectively. 2-Methyl-6-carbamoylpurine 12 was obtained from the reaction of imidazole 7 with pentane-2,4-dione. The same compound was observed in the ¹H nmr spectrum of a solution of 1,2-dihydropurine 9b in deuteriochloro-form. Benzylimidazole 7 can be acetylated with acetic anhydride leading to compound 14 . This, in solution, undergoes an acyl migration reaction to give imidazoles 15 and 17 . Imidazole 15 cyclizes in the presence of base to the corresponding 6-cyanopurine 16 . A solution of 14 in methanol is slowly converted into the 6-methoxypurine 18 , possibly via a methoxymidoyl intermediate. A similar intermediate 13 has been isolated from 7 in methanol.