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.
Highlights
Since the commercialization of Prontosil [1] as a drug in 1935, intense surveys have been made and a huge number of sulfonamide derivatives and their biological applications have been reported [2,3,4,5,6,7,8,9,10,11]
Searching for a simple and efficient method for the synthesis of novel sulfonamides under mild conditions is of ongoing concern [21,22]
The desired products 4a–c and 5a–c were isolated by normal acidification with 10% HCl with excellent yields and purities as observed by spectral data (Figures S1–S6, Supplementary Materials) and single crystal X-ray diffraction (Scheme 1)
Summary
Since the commercialization of Prontosil [1] as a drug in 1935, intense surveys have been made and a huge number of sulfonamide derivatives and their biological applications have been reported [2,3,4,5,6,7,8,9,10,11]. Several methods for the synthesis of sulfonamide from different substrates have been reported, for example, using sulfonyl chloride and amines [12,13] using a chlorinating agent with the corresponding sulfurated starting materials [14,15,16,17] or using non-conventional methods such as transition metals [18] or Grignard reagents [19]. Searching for a simple and efficient method for the synthesis of novel sulfonamides under mild conditions is of ongoing concern [21,22]. The use of sulfonyl chlorides and amines as starting materials still is the method of choice [23], where organic solvents and organic amine bases are used to scavenge the HCl generated from the reaction [24,25]. Water has been used as a green solvent for several chemical reactions because of safety and environmental concerns [28,29]
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