Abstract
In this work, we present the modified synthetic approaches that enables the efficient preparation of novel sulfonamides containing Schiff-base moieties. This is done by applying four modification process to the basic sulfanilamide SA 2 that initially transformed into its diazonium salt 21 under cold circumstances, which was then coupled with Active Methylene compounds (AMCs) 67(a-e) containing (Ethyl cyanoacetate (ECA), Ethyl acetoacetate (EAA), Ethyl benzo acetate (EBA), Dimethyl Malonate (DMM), and Methyl Thioglycolate (MTG) to form the unique azo-linked derivatives of SA 68 (a-e). The third phase was hydrazinolysis of this intermediate 68a, followed by nucleophilic addition of hydrazine hydrate 41 and intramolecular cyclization to produce a novel pyrazolone-based hydrazide molecule 69. Subsequently, the main amine group of the pyrazolone hydrazide linked to SP2 carbon was condensed with different aromatic aldehydes 70 (a-e) to produce structurally new Schiff bases 71 (a-e). The synthetic compounds were fully characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry with elemental analysis (CHN). The final Schiff bases have been evaluated for the biological activity, including antibacterial effectiveness. Molecular docking experiments were also performed to anticipate their binding interactions with target proteins with low and high biological activity (71a and 71e). Several of the newly synthesized Schiff base derivatives showed a strong biological activity, indicating their potential as multifunctional medicinal agents.
