Ring transformation of oxazoles to fused imidazoles. New synthetic route for 6-methyl-2,3-diphenyl-7,8-dihydroimidazo[1,2-b]pyridazine and 5-methyl-2,3-diphenyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole, and their perhydrobenzo analogues

Abstract

Fused imidazoles were synthesized by an intramolecular ring transformation of γ-keto-oxazoles with hydrazine and by an intramolecular dehydration of γ-amino-oxazoles. γ-Keto-oxazoles (4) and (6) were prepared by the reaction of lithiated 2-methyl-4,5-diphenyloxazole (1) with the methyl enol ether of an α-bromo ketone, followed by hydrolysis. γ-Keto-oxazoles (4) and (6) gave the 7,8-dihydroimidazo[1,2-b]pyridazine (7) and the 6,7,8,9,9a, 10-hexahydroimidazo[1,2-b]cinnoline (8), respectively, on treatment with hydrazine hydrate in acetic acid. The transformed fused imidazoles (7) and (8) were further converted into the corresponding tetrahydroimidazo[1,2-b]pyridazine (9) and octahydroimidazo[1,2-b]cinnoline (10), respectively, by reduction with NaBH₄. γ-Amino-oxazoles (11) and (12) were prepared from (4) and (6), respectively, on reduction with NaBH₃CN in the presence of ammonium acetate. The pyrolysis of (11) and (12) provided the cyclodehydrated 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (13) and 5,6,7,8,8a,9-hexahydro-4aH-imidazo[1,2-a]indole (14), respectively.