[Et3NH][HSO4]-mediated functionalization of hippuric acid: an unprecedented approach to 4-arylidene-2-phenyl-5(4H)-oxazolones

Abstract

A facile, green and stereoselective approach for the synthesis of azlactones/oxazolones 3(a–q) has been developed. The protocol involves reaction of hippuric acid and substituted heterocyclic/aromatic aldehydes in ionic liquid [Et₃NH][HSO₄] to yield the desired 4-arylidene-2-phenyl-5(4H)-oxazolones in excellent yields (94–97%) with a high degree of purity. The remarkable feature of this pathway is that the ionic liquid eliminates the use of toxic and expensive acetic anhydride and is endowed with catalytic and medium engineering ability. This eco-friendly approach improved synthetic efficiency (94–97% yield), minimizing the production of chemical waste without using highly toxic reagents for the synthesis and more notably, it promoted the selectivity for Z-azlactones/oxazolones. Density functional theory (DFT) calculations revealed that the Z-isomer of compound 3a is stabilised by 2.32 kcal mol⁻¹ more than the E-isomer. This synthetic scheme possesses diverse applicability and is compatible to a range of functional groups (electron donating/electron withdrawing).