New reaction of thiourea derivatives with dinitrogen tetroxide

Abstract

The thicurea derivatives have two active sites of both sulfur and nitrogen atom to be attacked by electrophile of nitrosonium ion (NO$^+$). We have found that treatment of thiourea derivative with dinitrogen tetroxide afford the corresponding disulfide or thiourea-S,S-dioxide. 1,3-Dicyclohexylthiourea reacts with dinitrogen tetroxide in dry acetonitrile under the nitrogen atmosphere to give 1,3-dicyclohexylthiourea-S,S-dioxide as major product. The reactions of cyclic thioureas such as 2-mercaptobenzimidazole, 2-mercaptopyrimidine, 2-mercaptobenzothiazole, 2-mercaptobenzoxazole, 6-ethoxy-2-mercaptobenzothiazole and 4,6-dimethyl-2-mercaptopyrimidine with half equimolar amount of dinitrogen tetroxide give the corresponding disulfides quantitatively in dry acetonitrile under mild conditions. Interesting reactions appear to proceed via the initial S-nitrosation by an attack of nitrosonium electrophile, and then a nucleophilic attack of sulfur atom of the remained substrates. Thus, dinitrogen tetroxide was found to be an excellent oxidizing agent for the synthesis of disulfides of heterocyclic compounds.