We present here a new proposal for the “one pot” generation of new 4-thiazolidinones (9a–e) through a multicomponent reaction under microwave irradiation conditions, using aromatic and heteroaromatic amines (8a–e), absolute ethanol as a “green” solvent and modifying the aldehyde group in the glycosidic residue, synthesized from D-mannitol. The study is focused in the variation of the irradiation times and the concentration of thioglycolic acid in order to study the possibility of controlling the structure and/or stereochemistry of the products formed in the reaction. Thiazolidinones 9a–d were obtained with a 69–82% The generation of the corresponding reaction products were monitored by TLC and CG-MS, taking reaction aliquots. The conditions reaction proved to be chemoselective depending on the excess of acid and irradiation times.

We report a solvent-free, microwave-assisted protocol for the synthesis of 2,2-disubstituted 1,3-oxathiolan-5-ones catalyzed by magnetite nanoparticles (MNPs). A design of experiments (DoE) approach was employed to optimize reaction parameters using the model reaction between acetophenone and 2-mercaptoacetic acid. Temperature, catalyst loading, and stoichiometry emerged as the most influential factors. Although the aromatic model substrate afforded modest yields (up to 24% by GC), the optimized conditions applied to aliphatic and cyclic ketones led to significantly higher yields, reaching up to 92%. This study highlights the value of combining heterogeneous nanocatalysis, microwave irradiation, and DoE to streamline optimization in heterocyclic synthesis.