A competitive reactivity study on the oxidative cyclization of thiosemicarbazones into 1,3,4-thiadiazolidines

Abstract In order to obtain useful insights on the mechanism of formation of 2(3H)-imino-1,3,4-thiadiazoles by oxidative cyclization of aldehyde thiosemicarbazones with Cu(II) or Fe(III) salts, a competitive reactivity study was performed on a suitable set of diversely substituted substrates, by means of HPLC techniques. This approach enabled to exploit Hammett’s equation without performing otherwise difficult-to-run kinetic experiments. The results presented herein support the hypothesis that the formation of the thiadiazole ring is induced by the attack of the oxidizing Lewis acid metal cation onto the imine-like nitrogen atom of the thiosemicarbazone substrate. Beyond mechanistic interpretation, the paper particularly focuses onto the methodological issues implied.