Rima Laroum, R. Boulcina, C. Bensouici
Nov 2, 2019
Citations
0
Influential Citations
10
Citations
Quality indicators
Journal
Organic Preparations and Procedures International
Abstract
Isoxazolone derivatives show significant biological and medicinal properties. They constitute excellent intermediates for the synthesis of numerous heterocycles and undergo several chemical transformations. A literature review shows that the best method for the synthesis of these molecules is a three-component reaction among aromatic aldehydes, ethyl acetoacetate and hydroxylamine hydrochloride under different catalysts and conditions. In continuing our research on new simple and environmentally friendly procedures for the preparation of heterocycles by multi-component reactions, we now report the synthesis of 4-arylmethylideneisoxazol-5(4H)-ones by the reaction among aromatic aldehydes, ethyl acetoacetate and hydroxylamine hydrochloride catalyzed by K2CO3. This commonly available base is very inexpensive, well-tolerated in organic agriculture, and safe; it has found wide use in numerous chemical transformations. Scheme 1 below shows the approach taken. We chose as our model system an equimolar mixture of 4-hydroxybenzaldehyde, ethyl acetoacetate and hydroxylamine chloride in a reaction catalyzed by different amounts of K2CO3. The selected model was subjected to different solvent and temperature conditions, as shown in Table 1. The best result was observed in Entry 8, with 5mol% catalyst in water at reflux for an hour (see Experimental Section). The optimum reaction conditions were applied to a number of aromatic and heteroaromatic aldehydes bearing different substituents. The results are summarized in Table 2. Reaction times were determined by thin layer chromatography in each case. Whatever the position of the substituent, yields were generally good to very good (between 64% and 85% and an average of 69%). Compounds 4k-4m are novel and reported here for the first time.