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

Abstract

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.

Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties

“…Due to the hydrolysis of sulfonyl chlorides as a major competing reaction under these conditions (called modi ed Schotten-Baumann conditions), an excess of sulfonyl chloride is necessary to ensure complete conversion of the amine [120]. For both protocols, the isolation and puri cation of the sulfonamide are not always straightforward because of the side products that are formed [121].…”

Synthesis, Characterization and Antimicrobial Activity of N-Pyridin-3-yl-benzenesulfonamide

“…The procedure reported by Almarhoon et al [15] with slight modification was adopted. A mixture of 3-aminopyridine (3.0 g, 0.032 mol) and benzene sulphonylchloride (3.0 mL, 0.032 mol) was gently introduced into a round bottom flask containing (25.0 mL, 2.0 M) Na 2 CO 3 aqueous solution and stirred for 2 hours.…”

Synthesis, structure, hirshfeld surface analysis, non-covalent interaction, and in silico studies of 4-hydroxy-1-[(4-nitrophenyl)sulphonyl]pyrrolidine-2-carboxyllic acid

“…Other methods also exist some of which involve the use of transition metals as catalysts [19], N-chlorosulponyl carbamate as a sulfonylating agent at 0 o C [20][21][22], conversion of methyl sul nates into sul namides, and subsequent oxidation to sulphonamides [23]. Milder synthetic conditions including the use of water as solvents and microwave irradiation for sulphonation of amines have been recently explored [24][25][26][27]. These methods do however suffer some setbacks ranging from low reactivity, use of more catalysts to increase yield, metal contamination, and di culty in catalyst recovery to complex puri cation steps.…”