Synthesis, Characterization and Anti-Microbial Evaluation of Substituted Isoxazole Derivatives

The prevalence of isoxazole cores in natural and biologically active molecules has stimulated the need for elegant and efficient ways to make these heterocycles as lead. A systematic investigation of this class of heterocycle revealed that isoxazole containing pharmacoactive agent's possess analgesic, anti-inflammatory and antimicrobial activities. 4-(5'- substituted-aryl-4,5'-dihydro-isoxazole-3'-yl-amino) phenols possessing potent biological activities. N-(4'- hydroxyphenyl) acetamide (2) was synthesized by the condensation of p-amino phenol (1) with acetyl chloride by refluxing in alkaline medium for 20 minutes. 3-substituted N-(4'-hydroxyphenyl) propanamides (3a-g) were prepared by the reaction of N-(4-hydroxy phenyl) acetamide with various substituted aryl aldehydes by refluxing for 6 hours in ethanol. The resultant compounds on refluxing for 6 hours with hydroxylamine hydrochloride gave the title compounds 4-(5'-substituted-aryl-4', 5'-dihydro-isoxazole-3'-yl-amino) phenols (4a-g). The synthesized derivatives have been characterized by FT-IR, 1HNMR and Mass spectral analysis. All the derivatives synthesized were screened for their anti-bacterial and antifungal activities at the concentration level of 100 μg/ml by cup-plate method. Some of the compounds such as 4a, 4b, 4c, 4d and 4f have shown significant antibacterial and antifungal activity when compared to standard drugs Ciprofloxacin (antibacterial activity) and Clotrimazole (antifungal activity). The results obtained indicate that, when the phenyl group at 5^th position of isoxazole nucleus contains the substituents as electron withdrawing atoms/groups particularly at ortho and meta positions could be a decisive factor for the compounds to have the increased potency over the other positions.