A Facile and Eco-Friendly Method for the Synthesis of Sulfonamide and Sulfonate Carboxylic Acid DerivativesX-ray Structure, Hirshfeld Analysis and Spectroscopic Characterizations

The search for a simple and efficient method for the synthesis of sulfonamide and sulfonate derivatives under mild and eco-friendly conditions is of continuing interest. Sulfonyl chlorides are still the best choice as starting materials for the preparation of target products. Here, we report a simple, efficient and eco-friendly method for the synthesis of sulfonamide and sulfonate carboxylic acid derivatives under green conditions using water and sodium carbonate as HCl scavengers to produce the products with high yields and purities. Two derivatives, 4-(tosyloxy)benzoic acid (5a) and 4-((4-methylphenyl)sulfonamido)benzoic acid (5b), were reacted with 2-morpholinoethan-1-amine under green conditions, where OxymaPure/diisopropylcarbodiimide (DIC) was used as a coupling reagent and 2-MeTHF as a solvent to give the target product with high yield and purity. nuclear magnetic resonance (NMR) and elemental analysis confirmed the structures of all obtained products. X-ray crystallography confirmed the structures of products 4b, 4c and 7a. The molecular packing of the three compounds (4b, 4c and 7a) was analyzed using Hirshfeld topology analysis. Mainly, H...O hydrogen bonding interactions dominated the packing. These methods of preparation and coupling merit further attention for the development of new derivatives that might have significant biological applications.