SYNTHESIS OF 4-DISUBSTITUTED 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 H-1 nmr spectrum of a solution of 1,2-dihydropurine 9b in deuteriochloroform. 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.