A sustainable approach to the synthesis of 2-arylimidazo[1,2-a]pyridines followed by sequential amino and bromo functionalization

Abstract

A sustainable and practical protocol has been developed for accessing 2-arylimidazo[1,2-a]pyridine derivatives using 2-aminopyridine derivatives, acetophenones, and carbon tetrabromide under solvent-free conditions. CBr4 has been used for the first time to promote the synthesis of 2-arylimidazo[1,2-a]pyridines. This method enables C3 amino-functionalization under oxidant-free conditions, as well as C3 bromo-functionalization using K₂S₂O₈ in a one-pot sequential manner, thereby enhancing operational simplicity and efficiency. The current protocol does not require an additional bromine source, such as NaBr or N-bromosuccinimide (NBS), for bromine functionalization at the nucleophilic site of imidazopyridine. In contrast, CBr4 serves a dual purpose by acting as a source for the bromination of acetophenones and as a bromine source for the sequential C3 bromo-functionalization. The protocol delivers corresponding products in good to excellent yields, highlighting its efficiency and versatility as a valuable tool in green synthetic chemistry.