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

Abstract

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.