Mechanochemical Approach for Metal‐Free Regioselective C5‐Sulfenylation of Imidazo[2,1‐b]thiazoles

The development of sustainable and selective methodologies for heterocyclic functionalization remains a key challenge in organic synthesis. In this study, we report a novel, metal‐free bis(trifluoroacetoxy)iodo]benzene (PIFA)‐mediated strategy for the regioselective C5‐sulfenylation of imidazo[2,1‐b]thiazoles using aryl methyl sulfides under mechanochemical conditions. This solvent‐free approach offers a rapid, efficient, and environmentally friendly alternative to current methods, achieving yields of up to 86% while completely avoiding hazardous solvents. The method exhibits broad substrate scope, with tolerance to both electron‐donating and electron‐withdrawing functional groups. This mechanochemical strategy provides a valuable synthetic tool for the functionalization of imidazo[2,1‐b]thiazole scaffold, with potential applications in medicinal and materials chemistry.