Green synthesis of novel acylsulfonyl hydrazide derivatives: high regioselectivity in Michael reaction

Abstract In this study, a highly regioselective and green synthetic method was developed for the synthesis of novel N ′-alkylated acylsulfonyl hydrazide derivatives via the aza-Michael reaction between acylsulfonyl hydrazides and α,β-unsaturated esters. This reaction was carried out efficiently under solvent-free conditions at room temperature in the presence of potassium carbonate as a mild base and tetrabutylammonium bromide (TBAB) as an ionic liquid Media. A wide range of substrates, including compounds with electron-donating and electron-withdrawing substituents on the aromatic ring, as well as various alkyl chains in acrylate esters, were successfully converted to the corresponding products in good to excellent yields (58–88%). The method exhibited very high selectivity, directing the alkylation preferentially to the sulfonamide nitrogen atom over the amide nitrogen, which can be explained by charge distribution and stabilization effects. DFT calculations further supported this observation. The structures of all synthesized products were confirmed by IR, 1 H NMR, 13 C NMR spectroscopy, along with Mass spectroscopic data of 7c, 7f., 7i, CHN analysis of derivative 7f., and single-crystal diffraction analysis of compound 7c. This protocol provides a practical, mild, and efficient method for the synthesis of functionalized hydrazide derivatives and contributes to the advancement of green and selective methods for C–N bond formation.