A Practical and Metal-Free Multicomponent Route to Bis(thiazolidinone) Derivatives

A practical and efficient multicomponent synthetic approach has been developed for the preparation of bis(thiazolidin-4-one) derivatives via the reaction of aromatic aldehydes, thioglycolic acid, and benzene-1,4-diamine. This method proceeds under mild, metal-free, and catalyst-free conditions using toluene as the solvent. A diverse library of nine derivatives bearing various substituents on the aromatic ring was synthesized, demonstrating the protocol's broad functional-group tolerance. In addition, high yields of up to 99% were achieved for the target compounds, highlighting the effectiveness of the approach. Noteworthy, the operational simplicity, high atom economy, and absence of transition metals make this methodology particularly attractive for the rapid assembly of thiazolidinone- based scaffolds. These heterocyclic frameworks are of significant interest due to their welldocumented biological activities. Overall, this work provides a valuable contribution to the field of diversity-oriented synthesis and offers a sustainable route for the generation of bioactive heterocycles.