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. Issue 9 (23rd January 2014)

• Record Type: Journal Article
• Authors: Raghava, Byregowda; Parameshwarappa, Gangajji; Acharya, Anand; Swaroop, Toreshettahally R.; Rangappa, Kanchugarakoppal S.; Ila, Hiriyakkanavar
• Is Part Of: European journal of organic chemistry. Issue 9(2014)
• Page Start: 1882
• Page End: 1892
• Publication Date: 2014-01-23
• Subjects: Synthetic methods -- Nitrogen heterocycles -- Oxygen heterocycles -- Regioselectivity -- Cyclization; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201301667
• Languages: English
• ISSNs: 1434-193X

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‐diketones1 or with 3‐methylthio‐1, 3‐bis(het)aryl‐2‐propenones2 under various reaction conditions. In the first protocol, diketones1 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)arylisoxazoles5, 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‐propenones2 in the presence of barium hydroxide in refluxing ethanol gave 3, 5‐bis(het)arylisoxazoles6 with complementary regioselectivity in high yields. A probable mechanism for the formation of regioisomeric isoxazoles5 and6 from precursors1 and2 has been suggested. Abstract : The synthesis of 3, 5‐unsymmetrically substituted isoxazoles with complementary regioselectivity is reported. The reaction occurs by cyclocondensation of hydroxylamine with suitably substituted monothio β‐diketones and 3‐(methylthio)‐2‐propenone precursors, which act as 1, 3‐electrophilic building blocks, under various reaction conditions, and the products are formed in excellent yields.