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

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