High yield solvent-base-controlled, transition metal-free synthesis of 4,5-functionalized 1,2,3-thiadiazoles and 1,2,3-triazoles from 2-cyanothioacetamides and sulfonyl azides is described. Under diazo transfer conditions in the presence of a base in an aprotic solvent 2-cyanothioacetamides operating as C-C-S building blocks produce 5-amino-4-cyano-1,2,3-thiadiazoles exclusively. The use of alkoxide/alcohol system completely switches the reaction course due to the change of one of the reaction centers in the 2-cyanothioacetamide (C-C-N building block) resulting in the formation of 5-sulfonamido-1,2,3-triazole-4-carbothioamide sodium salts as the only products. The latter serve as good precursors for 5-amino-1,2,3-thiadiazole-4-carboximidamides, the products of Cornforth-type rearrangement occurring in neutral protic medium or under acid conditions. According to DFT calculations (B3LYP/6-311+G(d,p)) the rearrangement proceeds via intermediate formation of a diazo compound, and can be catalyzed by acids via the protonation of oxygen atom of the sulfonamide group.

The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides 1 with various types of azides 2 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 5 and 1,2,3-triazole-4-carbothioamides 4. This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines 2′o 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 N,N′-bis-(2-cyanothiocarbonyl)­pyrazine 1h with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles 8 and 1,2,3-triazoles 9 connected via a 1,1′-piperazinyl linker. 2-Cyanothioacetamides 1 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 11. In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones 2o–q react with cyanothioacetamides to form N-pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4-N-l-carbimidamides 12. A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides.

The reactions of primary and tertiary malonothioamides with aryl and sulfonyl azides can take place in three directions, depending on the nature of the thioamides and azides. Ethoxycarbonylthioacetamide reacts with aryl azides with the formation of ethyl 5-amino-1-aryl-1,2,3-triazole-4-carboxylates. In reaction with aryl azides tertiary thioamides of cyanoacetic acid form 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides, and in reaction with tosyl azide they form 5-amino-4-carboxamidino-1,2,3-thiadiazoles. Hypothetical mechanisms for the transformations are discussed.

Reactions of functionalized [CN, CO2Et, C(O)NHR, C(S)NR1R2] derivatives of thiomalonic acid and 2‐arylthioacetamides with sulfonyl azides were shown to give active‐methylene N‐sulfonylamidines in 62–98 % yields. Various procedures for the reactions, including the use of pyridine, boiling ethanol, and water, or running the reactions in the absence of a base and solvent at 80 °C, were carried out and compared. The solvent‐free variant was the best in terms of yield, and also because it does not require the use of an excess of the toxic and hazardous azides. The reaction was shown to tolerate electron‐withdrawing substituents such as carbonyl, cyano, and aryl groups at the C‐2 position. The presence of alkyl and phenyl groups on the nitrogen atom of the thioacetamide fragment, and the presence of substituents on the sulfonyl group were also tolerated. Thus, an efficient solvent‐free, catalyst‐free, and base‐free synthetic approach for the synthesis of N‐sulfonylmalonacetamidines and 2‐arylacetamidines was found.

A design and a convenient approach for the synthesis of novel N-sulfonyl-2-diphenylmethylsulfinylacetamidines have been demonstrated by starting from benzhydrylsulfanylacetic (BSA) acid. This approach involves a sequential amidation with amines, thionation with Lawesson's reagent, iminosulfonylation with sulfonyl azides, and oxidation of sulfide fragment with hydrogen peroxide. The key step of this transformation (reaction of thioamides with sulfonyl azides) was carried out either in ethanol or in the absence of any solvent. The synthesized compounds were tested in cells for inhibition of dopamine transporter. Among the synthesized compounds, two products were found to be in a similar range of activity as the well-known dopamine transporter inhibitor, modafinil.