Abstract

An expeditious, metal-free protocol has been demonstrated for the synthesis of isoxazolone derivatives using domino multi-component strategy. The envisaged methodology involves the L-valine promoted three-component cyclo-condensation reaction of alkylacetoacetates, hydroxylamine hydrochloride and aldehydes in ethanol under reflux. The reaction proceeded to deliver the desired products in good to excellent yields (74–97%), exhibited good functional group tolerance and completed in less than 4 min with most of the substrates. High yields, short reaction time, noncorrosive organocatalyst, mild reaction conditions, clean reaction profiles and the absence of any tedious workup or purification are the beneficial features of this process. Moreover, quantum computational study has been performed at B3LYP/6-311G++(d, p) level to investigate the various DFT based molecular descriptors, HOMO–LUMO energy gap and electrostatic potential surface properties of the synthesized product.

Graphic abstract

An improved protocol for the synthesis of 3,4-disubstituted isoxazol-5(4H)-ones through L-valine-mediated domino three-component strategy

中文翻译：

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通过L-缬氨酸介导的多米诺三组分策略合成3,4-二取代的异恶唑-5（4 H）-ones的改进的协议

摘要

已证明使用多米诺多组分策略可快速合成不含金属的方案，用于合成异恶唑酮衍生物。设想的方法涉及在回流下由L-缬氨酸促进的乙醇酸烷基酯，羟胺盐酸盐和醛在乙醇中的三组分环缩合反应。反应以良好至极佳的收率（74–97％）交付所需的产物，表现出良好的官能团耐受性，并且大多数底物在不到4分钟的时间内完成。高收率，较短的反应时间，无腐蚀性的有机催化剂，温和的反应条件，清洁的反应曲线以及没有繁琐的后处理或纯化是该方法的有益特征。此外，已经在B3LYP / 6-311G ++（d，

图形摘要

通过L-缬氨酸介导的多米诺三组分策略合成3,4-二取代的异恶唑-5（4 H）-ones的改进的协议