Water/Alkali-Catalyzed Reactions of Azides with 2-Cyanothioacetamides. Eco-Friendly Synthesis of Monocyclic and Bicyclic 1,2,3-Thiadiazole-4-carbimidamides and 5-Amino-1,2,3-triazole-4-carbothioamides.

The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides with various types of azides in water in the presence of alkali presents an efficient, general, one-step, atom-economic, and eco-friendly method for the synthesis of 1,2,3-thiadiazol-4-carbimidamides and 1,2,3-triazole-4-carbothioamides . This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides. The method was furthermore applied to the reaction of ,'-bis-(2-cyanothiocarbonyl)pyrazine with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles and 1,2,3-triazoles connected via a 1,1'-piperazinyl linker. 2-Cyanothioacetamides were also shown to react with aromatic azides in water in the presence of alkali to afford 1-aryl-5-amino-1,2,3-triazole-4-carbothioamides . In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones react with cyanothioacetamides to form -pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4--l-carbimidamides . A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides.