A Facile Synthesis of Isoxazolone Derivatives Catalyzed by Cerium Chloride Heptahydrate in Ethyl Lactate as a Solvent: A Green Methodology

Background: Synthesis of heterocyclic compounds containing the isoxazole structural unit is important, as many of these compounds and their derivatives show biological activity. The use of green solvents in organic synthesis is an area of extensive research and several green solvents like water, ionic liquids, polyethylene glycol and some bio based solvents have been reported in the literature. The current paper discusses the synthesis of a series of arylmethylidene isoxazolone derivatives by a one pot three component condensation reaction between ethyl acetoacetate, hydroxylamine hydrochloride and aromatic aldehydes, in the presence of cerium chloride heptahydrate, a mild water tolerant Lewis acid as a catalyst and 70% ethyl lactate as the solvent. Methods: Several isoxazolone derivatives were synthesized by the developed protocol and they were characterized by m.p., IR, 1H NMR, CMR, HRMS and comparison with reported data. Results: Good to moderate yields of the desired isoxazolone derivatives were obtained with aldehydes having electron releasing substituents as well as pi excessive heterocycles. In addition, as compared to previous reports, the reaction yields the desired product in moderate yields with halo substituted aldehydes as well. Conclusion: We have developed a protocol with easy workup for the facile synthesis of isoxazol- 5(4H)- ones using cerium chloride heptahydrate in 70% ethyl lactate which is a biodegradable solvent. The reaction is carried out at room temperature and the catalyst and solvent are recyclable up to three times without appreciable loss in activity.