Reactions of Thioacetamide Derivatives with Sulfonyl Azides: An Approach to Active‐Methylene N‐Sulfonylacetamidines

Abstract

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.

Progress in intermolecular and intramolecular reactions of thioamides with diazo compounds and azides

“…However, this novel reaction remains the only example of formation of amidines from the reaction of thioamides with aryl azides. In contrast to aromatic azides, the highly electrophilic sulfonyl azides were shown by Zelenskaya et al [63] and other groups following up on this report [64][65][66][67][68][69] to be more prone to react with thioamides to form N-sulfonyl amidines. Thus Zelenskaya et al discovered that thioamides of acetic and benzoic acid 80 reacted with tosyl azide 81 in pyridine to form N-tosylamidines 82 in 73-86% yields (Scheme 23) [63].…”

Design and Synthesis of N-Sulfonylamidines of Modafinic Acid

“…The known method for the synthesis of N-sulfonylamidines by alkylation reaction followed by treatment of alkyl thioimidates with amines 25 and then with sulfonyl chlorides was shown to give moderate overall yields and was ruled out from consideration. Therefore, we used the sulfonylimination approach 17,18 for the synthesis of N-sulfonylamidines of BSA. To generate sulfonylimino group, thioamides 2a-d were treated with a variety of sulfonyl azides 3a-e bearing methyl, aryl, or heteroaryl moieties either in boiling ethanol (Scheme 2) ( Table 1, entries 1, 3, 5, 6, 8, 10, 11, 13, 14, 16, 17, 19, 20) or without using any solvent (entries 2, 4, 7,9,12,15,18,21).…”

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

“…However, no efficient and general method to prepare a series of heterocyclic N -sulfonyl amidines has been elaborated so far. A new approach to N -sulfonyl amidines has been published recently, based on the reaction of thioamides with sulfonyl azides [ 33 , 41 – 42 ] ( Fig. 2 ).…”