Synthesis of Imidazo[4, 5-e][1, 4]diazepine and Imidazo[4, 5-e][1, 4]-oxazepine Derivatives Using Caffeidine, a Hydrolysis Product of Caffeine

Abstract

Synthesis of imidazo[4, 5-e][1, 4]diazepines using caffeidine (1) was studied. Caffeidine was condensed with various α, β-unsaturated carboxylic acid derivatives to give N-(α, β-unsaturated acyl)caffeidines (4). Intramolecular Michael addition of 4 having an electron-withdrawing group at the β-position of the α, β-unsaturated acyl group afforded imidazo[4, 5-e][1, 4]diazepines (5, 6). Compounds of the same type (14) were also prepared by treatment of N-(α-halogenoacyl)caffeidines (13) with EtONa in abs. EtOH. On the other hand, heating of 13 in H₂O gave imidazo[4, 5-e][1, 4]oxazepines (15). Compounds 5d, 15b, and 15c showed arterial relaxing activities.