An Improved Synthesis of 3-Methyl-4-nitro-5-heteroarylethenylisoxazoles

A high yielding synthesis of polyfunctional scaffold 3-methyl-4-nitro-5-heteroarylethenylisoxazole is described.The novel condition allowed the preparation of reactive title compounds in high yield.N O NO 2 Ar O NO 2 N O Ar 1 electrophilic centres E 1 + E 2 + 2 3 Figure 1 Polyfunctional scaffold 5-styryl-4-nitroisoxazole 1Compounds 1 could be prepared from the condensation of commercially available 3,5-dimethyl-4-nitroisoxazole 2 and an aromatic aldehyde 3 (Figure 1).HETEROCYCLES, Vol.71, No. 5, 2007 1173While several compounds 1 have been reported in which Ar is represented by a substituted phenyl ring, 7,8 only a few examples have been described in which Ar is of heterocyclic nature. 9,10][9][10] This procedure failed at producing in particular compounds bearing additional electron-withdrawing groups.For example, while isoxazole 2 was efficiently reacted with furfural 3a to give 5-styrylisoxazole 1a in good yield, the reaction of 2 with 5-nitrofurfural gave a complex mixture of products.Therefore the synthesis of 1b, which was found possessing antibacterial activity, required the condensation of 2 and 3a and successive nitration of the resulting 1a (Scheme 1).