An Expeditious Synthesis of Ethyl-2-(4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3- yl)acetate Derivatives

Abstract

In this contribution, an operationally simple and efficient synthetic procedure for synthesizing derivatives of 4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3-yl)acetate has been developed. This interesting synthetic protocol involves the one-pot cyclocondensation of diethyl 3-oxopentanedioate, aryl or heteroaryl aldehydes, and hydroxylamine hydrochloride catalyzed in an aqueous medium using an azolium salt as a robust organo-catalyst. In this work, for the first time, 1,3-dibenzyl-1H-benzo[d]imidazol-3-ium chloride was used as the catalyst for the synthesis of ethyl-2-(4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3-yl)acetate derivatives from the commercially available starting materials. Notably, no by-products were observed during the multicomponent reaction. Optimization studies revealed that 5 mol% of 1,3-dibenzyl-1H-benzo[d]imidazol-3-ium chloride is sufficient to perform the experiment. Furthermore, examining the results of the temperature conditions showed that 70 ºC is the best temperature to carry out the reaction. In an optimization study, H2O was the most effective solvent to perform the three-component cyclization reaction. In this method, using H2O as the environmentally benign and inexpensive reaction medium, so from the point of view of the reaction medium, it can be said that this three-component heterocyclization obeys the principles of green chemistry. This procedure has several advantages, such as good to excellent yields, reasonable reaction times, isolation of heterocyclic products without column chromatography or other chromatographic methods, atom-economy, step-economy, and clean reaction profiles. background: Isoxazole-5(4H)-ones are the significant class of isoxazoles, which are used in nonlinear optical materials, filter dyes, molecular devices, and solar cells. Several structures of isoxazole-5(4H)-ones displayed eye-catching biological properties. On the other hand, azolium salts as important nitrogen-containing heterocycles are quaternary ammonium compounds with acidic hydrogen at 2-position, which are used as precursors for N-heterocyclic carbene (NHC) synthesis and also act as the catalyst in organic reactions. conclusion: This procedure has several further advantages, such as good to excellent yields, reasonable reaction times, isolation of heterocyclic products without column chromatography or other chromatographic methods, atom-economy, step-economy, and clean reaction profiles. other: The heterocyclic products characterized using NMR and elemental analysis.