Abstract

Benzimidazoles are core scaffolds in numerous pharmacologically active compounds. Their synthesis typically involves acid-catalyzed condensation of o-phenylenediamine with carboxylic acids or aldehydes under batch conditions, often resulting in low atom economy and high energy use. This study presents a continuous flow process for benzimidazole synthesis using a sulfonated polystyrene resin as a heterogeneous acid catalyst. Reaction parameters including residence time, flow rate, and temperature were optimized to achieve high yields with minimal by-product formation. The continuous process yielded benzimidazole derivatives in 90–97% yield within residence times of less than 10 minutes, with excellent scalability and catalyst recyclability over 20 cycles. This method offers a sustainable, intensified route suitable for industrial manufacturing of benzimidazole-based APIs.