Eikoh Ito

Synthesis of cyclopentano[c]-s -triazoles by the intramolecular ring transformation of 1,3,4-oxadiazoles

Cyclopentano[c]-s-triazoles were synthesized by intramolecular ring transformation starting from y-keto-l,3,4-oxadiazoles 5 and 9. The required functionality for this intramolecular reaction was established by (i) the reaction of lithiated 2-methyl-l,3,4-oxadiazole 4 with the methyl enol ether of α-bromo ketones followed by hydrolysis; (ii) reductive amination of γ-ketones 5 and 9 to further reorganized hydrazide 7 and y-amino-l,3,4-oxadiazole 9 with NaBH3CN; and (iii) pyrolysis of 7 and γ at 280° (5 mmHg) to the cyclopentano[c]-s-triazoles 8 and 11. By the same treatment, the S-connected analogue 2 afforded the desired fused s-triazole 17.

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

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.