Switchable Synthesis of 4,5-Functionalized 1,2,3-Thiadiazoles and 1,2,3-Triazoles from 2-Cyanothioacetamides under Diazo Group Transfer Conditions

Abstract

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.

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

“…The synthesis of complexes of bis(sulfonyl amidines) 3aj-an with metals is in progress. 154.1-159.7 ppm which is close to 156 ppm which is the value found for N-sulfonyl amidines of 1,2,3-thiadiazole-4-carboxylic acid prepared by another method [22] and was clearly different from the thioamide carbon signal at 185-187 ppm in the 13 C NMR spectra of starting materials 1. A final proof of the structures of the prepared compounds comes from the X-ray data for 3e,t,ag (Schemes 2, 3, and 5).…”

“…An N-sulfonyl amidine was recently found to be a key group in acid-base-induced rearrangements of 1,2,3-triazoles and thiadiazoles [22]. A variety of methods have been developed for the synthesis of N-sulfonyl amidines.…”

“…A variety of methods have been developed for the synthesis of N-sulfonyl amidines. The most commonly used methods to prepare these compounds include the Cu-catalyzed multicomponent reaction of alkynes, sulfonyl azides and amines [23][24][25][26][27][28][29][30][31], the reaction of thioacetamide derivatives and cyclic thioamides with sulfonyl azides [22,32,33], the chlorophosphite-mediated Beckmann reaction of oximes with p-toluenesulfonyl azide [34], the sulfonyl ynamide rearrangement by treatment with amines [35], the sodium iodide catalyzed reaction of sulfonamide with formamide [36], and the condensation of sulfonamide derivatives with DMF-DMA [37].…”

“…A few representatives of N-sulfonyl amidines of heteroaromatic acids have been prepared and applied [22,32,[38][39][40]. However, no efficient and general method to prepare a series of hetero-cyclic N-sulfonyl amidines has been elaborated so far.…”

Design and synthesis of N-benzimidazol-2-yl-N'-sulfonyl acetamidines

“…Thioamides 2c,d did not react with sulfonyl azides 1a,b in water, though this solvent was successfully used to prepare other types of amidine. 14,16 The reason may involve the very low solubility of thioamides 2 in water. Luckily, the reaction of (benzimidazol-2-yl)ethanethioamides 2a-h with azides 3a-g occurred when the mixture of thioamides 2 and sulfonyl azides 3 in equivalent ratio (for the reaction of thioamide 2f with azide 3c 5.0 equiv.…”