Synthesis of 2-trifluoromethyl benzimidazoles, benzoxazoles, and benzothiazoles via condensation of diamines or amino(thio)phenols with CF3CN.

A new and efficient method is developed for the synthesis of 2-trifluoromethyl benzimidazoles, benzoxazoles, and benzothiazoles in good to excellent yields by the condensation of diamines or amino(thio)phenols with in situ generated CF3CN. Additionally, the synthetic utility of the 2-trifluoromethyl benzimidazole and benzoxazole products is demonstrated via gram scale synthesis. The mechanistic study suggests that the reaction proceeds via the nucleophilic addition of trifluoroacetonitrile to the amino group of the diamine derivatives to form an imidamide intermediate, followed by intramolecular cyclization.

Synthesis of 2-trifluoromethyl thiazoles via [3 + 2] cycloaddition of pyridinium 1,4-zwitterionic thiolates with CF3CN.

2,2,2-Trifluoroacetaldehyde O-(aryl)oxime was employed for the [3 + 2] cycloaddition of pyridinium 1,4-zwitterionic thiolates for the synthesis of 2-trifluoromethyl 4,5-disubstituted thiazoles. The reaction works well with various substituted pyridinium 1,4-zwitterionic thiolates in moderate to good yields. The synthetic potential of the obtained 2-trifluoromethyl 4,5-disubstituted thiazoles was demonstrated.