This study presents an efficient and sustainable method for synthesizing 1,3-oxathiolan-5-ones, a class of sulfur- and oxygen-containing heterocycles with relevance in medicinal chemistry and organic synthesis.[1] The method employs a novel heterogeneous catalytic system based on magnetite nanoparticles (MNPs) to promote the intramolecular cyclodehydration of commercial ketones with thioglycolic acid under microwave irradiation. Unlike conventional approaches, typically limited to aldehydes, this solvent-free protocol enables the use of ketones, achieving excellent yields in just 40 minutes at 90 °C using 10 mol% of MNPs and 250 W microwave power.

A design of experiments (DoE) approach was used to optimize the reaction parameters, revealing that irradiation time and the presence of MNPs were the most significant factors affecting the yield. Under optimized conditions, different 1,3-oxathiolan-5-ones were obtained in excellent yields and isolated via simple crystallization.

Importantly, the MNPs exhibited remarkable reusability, retaining their catalytic activity over five consecutive cycles with no significant loss in performance. Their magnetic nature enabled straightforward recovery using an external magnet, enhancing the process sustainability.

This work highlights the advantages of microwave-assisted organic synthesis (MAOS) for achieving rapid, clean, and energy-efficient transformations.

The synergy between MNP catalysis, microwave activation, and statistical optimization offers a powerful strategy for the preparation of heterocycles, paving the way for the future development of bioactive molecules.

[1] (a) Al-Majedy, Y.K. et al., Bioorg. Med. Chem. 2016, 24, 317–324. (b) Hassan, M.Z. et al., Bioorg. Chem. 2016, 67, 127–141. (c) Cihlar, T.; Ray, A.S., Antiviral Res. 2010, 85, 39–58.