A simple, convenient, environmentally friendly, and sustainable green protocol has been developed for the synthesis of biologically significant 5-substituted 1,2,4-triazolidine-3-thiones in excellent yields (72–97%). This green method involves a one-pot condensation between aldehydes or ketones with thiosemicarbazide at 70 °C, employing sustainable aqueous onion extract as a green catalyst in water as the reaction medium. A wide range of substrates, including aryl, heteroaryl, and aliphatic aldehydes or ketones, were efficiently transformed into the corresponding 1,2,4-triazolidine-3-thiones 3 or spiro 1,2,4-triazolidine-3-thiones 5 with high yields. Water, as a green solvent, enables the reaction to proceed smoothly while supporting a sustainable synthetic protocol. The present methodology aligns well with green chemistry principles by utilizing a biodegradable catalyst, an eco-friendly solvent, avoiding column chromatography, reducing reaction time, and achieving high yields with improved atom economy. Furthermore, in silico ADME profiling of all synthesized triazolidine-3-thione derivatives was performed using the SwissADME online tool to evaluate their drug-likeness, including BBB permeability, oral bioavailability, compliance with Lipinski’s rule of five, and synthetic accessibility. Among the synthesized compounds, the selected derivatives, such as 3a , 3c , 3d , 3q , and 5a , demonstrate a more balanced pharmacokinetic profile. Aqueous Onion Extract Catalyzed Sustainable and Green Synthesis of 5-Substituted 1,2,4-Triazolidine-3-thiones in Water and In silico ADME Evaluation
Ramasamy et al. (Thu,) studied this question.