Eco-friendly synthesis and antifungal evaluation of N-substituted benzimidazoles

Abstract

A convenient synthesis of N-phenacylbenzimidazoles in high yields (90–95%) by the N-alkylation reaction of 1H-benzimidazole with phenacyl bromides is provided. The carbonyl group reduction in the products offered the respective N-(2-aryl-2-hydroxyethyl)benzimidazoles in yields up to 97%. In the optimization of reaction conditions for preparing these N-substituted benzimidazoles (ketones and alcohols), a comparative study between eco-friendly methods (microwave and ultrasound) and conventional heating is described. These antifungal azoles analogs were tested for in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, where the alcohols chlorine substituted (4-Cl and 2,4-Cl2) showed the best activity (MIC50 = 31.2 × 10–6 g/cm3).