Cyclocondensation of Hydroxylamine with 1,3‐Bis(het)arylmonothio 1,3‐Diketones and 1,3‐Bis(het)aryl‐3‐(methylthio)‐2‐propenones: Synthesis of 3,5‐Bis(het)arylisoxazoles with Complementary Regioselectivity

Abstract

Abstract Efficient routes for the regioselective synthesis of 3,5‐bis(het)arylisoxazoles with complementary regioselectivity have been developed. The methods involve the cyclocondensation of hydroxylamine hydrochloride with either 1,3‐bis(het)aryl‐monothio‐substituted 1,3‐diketones 1 or with 3‐methylthio‐1,3‐bis(het)aryl‐2‐propenones 2 under various reaction conditions. In the first protocol, diketones 1 were treated with hydroxylamine hydrochloride in the presence of sodium acetate/acetic acid (pH 2.2) in refluxing ethanol/benzene to give 3,5‐bis(het)arylisoxazoles 5 , in which the het(aryl) moiety attached to thiocarbonyl group of the monothio‐substituted 1,3‐diketones is installed at the 3‐position. On the other hand, the reaction of hydroxylamine hydrochloride with 3‐(methylthio)‐1,3‐bis(het)aryl‐2‐propenones 2 in the presence of barium hydroxide in refluxing ethanol gave 3,5‐bis(het)arylisoxazoles 6 with complementary regioselectivity in high yields. A probable mechanism for the formation of regioisomeric isoxazoles 5 and 6 from precursors 1 and 2 has been suggested.