Studies on Isoxazoles. XII. Novel Syntheses of 4-Isothiazolin-3-thiones and Bis (3-isoxazolyl) Disulfides from 4-Isoxazolin-3-thiones

• Published in: Chemical & pharmaceutical bulletin Vol. 28; no. 2; pp. 487 - 492
• Main Authors: SUGAI, SOJI, TOMITA, KAZUO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1980; Japan Science and Technology Agency
• Subjects: thermal oxidation
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.28.487

Heating of 2, 5-dimethyl-4-isoxazolin-3-thione (IIa) in acidic media gave 2, 5-dimethyl-4-isothiazolin-3-thione (IIIa) and bis (5-methyl-3-isoxazolyl) disulfide (IVa) in poor yields. On the other hand, 2-methyl-5-phenyl-4-isoxazolin-3-thione (IIe) afforded only bis (5-phenyl-3-isoxazolyl) disulfide (IVb). The reactions of 4-isoxazolin-3-thiones (IIa-d) with hydrogen sulfide or thioacetic acid in 48% hydrobromic acid gave 4-isothiazolin-3-thiones (IIIa-d) in moderate yields, while 5-phenyl-4-isoxazolin-3-thiones (IIe, f) afforded 3-imino-5-phenyl-1, 2-dithiols (VIe, f) in addition to 5-phenyl-4-isothiazolin-3-thiones (IIIe, f). A reaction mechanism is proposed. The thiol (VIe) was treated with base to give IIIe. An improved synthesis of the disulfides (IVa, b) was developed by the reaction of 2-methyl-4-isoxazolin-3-thiones (IIa, b) or 2-benzyl-4-isoxazolin-3-thiones (IIg, h) with bromine.