Hot Melt Extrusion Assisted Synthesis of 3-Methyl-4-arylmethyleneisoxazole-5(4H)-ones: A Continuous and Sustainable Approach

Abstract

A one-pot multicomponent reaction strategy was employed to synthesize 3-methyl-4-arylmethylene-isoxazole-5(4H)-ones from the aromatic/heteroaromatic aldehyde, 1,2-diketone, and hydroxylamine hydrochloride using the hot melt extrusion technique. The use of an extruder eliminates the need for solvents and catalysts, enabling a continuous, scalable, and environmentally friendly process. The protocol has promising features such as shorter reaction times, minimum waste, easy workup and scale-up procedures, broad substrate scope, and moderate to excellent yields. Also, the methodology demonstrates exceptional sustainability, with an E-factor of 0.05, an Eco scale score of 94, and a Process mass intensity of 1.63, thereby showcasing a greener and energy-efficient methodology.