Reactions of 5-substituted 3-alkyl- and 3-aryl-isoxazoles with tetrasulfur tetranitride antimony pentachloride complex (S4N4·SbCl5): complete regioselective formation of 4-substituted 3-acyl- and 3-aroyl-1,2,5-thiadiazoles and their mechanism of formation

Abstract

The reactions of 3-alkyl- 5a–f, 3-aryl- 5g–m, 3-acylamido- 5n,p, 3-benzamido- 5o and 3-arylamino- 5q -5-alkyl- and -5-aryl-isoxazoles with tetrasulfur tetranitride antimony pentachloride complex (S₄N₄·SbCl₅) in toluene at 90 °C to reflux temperature give 3-acyl- 6a–c, e, n–q and 3-aroyl-4-substituted-1,2,5-thiadiazoles 6d, f–m in 13 to 61% yields as single isomers. The same reactions of 3,4-dimethyl- 5s, 5v, 4-ethyl-3-methyl- 5t -5-alkyl- and/or 5-aryl-isoxazoles under the same conditions give 3-(1-acetyl-1-chloroethyl)- 8a, 3-(1-benzoyl-1-chloropropyl)- 8b, 3-(1-benzoyl-1-chloroethyl)- 8d, or 3-(1-benzoyl-1-chloroethyl)-4-methyl-1,2,5-thiadiazoles 8c, which are a new type of 1,2,5-thiadiazole derivatives. In addition the reactions with 5-aryl-4-bromoisoxazoles (5,w,y,z) having an electron-donating substituent such as methyl, 4-methylphenyl, and 4-methoxyphenyl groups at C3 under the same conditions afford 3-aroyl-4-substituted-1,2,5-thiadiazoles 6d, 6j and 6k, whereas the starting isoxazoles are recovered from the reactions with 5-aryl-4-bromoisoxazoles 5x,z′ having a phenyl or a 4-chlorophenyl group at C3. A plausible mechanism is proposed for the formation of the products.