The Synthesis of Adamantane Ring Containing Benzimidazole, Benzoxazole, and Imidazo[4,5-e]benzoxazole Derivatives from 3-Aminophenol

Adamantane derivatives containing heterocycles such as benzimidazoles, benzoxazoles, and fused imidazo[4,5-e]benzoxazoles were synthesized from 3-aminophenol. The route started with amidation of adamantane-1-carboxylic acid chloride with 3-aminophenol furnishing N-(3-hydroxyphenyl)adamantane-1-carboxamide. Subsequent nitration gave three regioisomers. After reduction of the nitro groups, the respective aniline derivatives were used in the formation of benzimidazole and benzoxazole rings. The cyclization of the 2-substituted benzoxazole ring was performed using two methods: via condensation of N-(2-amino-3-hydroxyphenyl)adamantane-1-carboxamide with carbonitriles in the presence of a Lewis acid or via Cu(II)-catalyzed oxidative coupling of aminophenol with aromatic aldehydes. The benzimidazole ring formed by acid-catalyzed cyclization of N-(2-amino-5-hydroxyphenyl)adamantane-1-carboxamide was then converted to a tricyclic system after three synthetic steps.