الفهرس 
Chapter 1Only 14 pages are availabe for public view
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Abstract
Sulfonamide unit has attracted synthetic organic chemists due to its expanded applications in medicinal chemistry1 as anticancer, anti-inflammatory, antimicrobial, anticonvulsant, and antiviral agents.2Being of a crystalline nature is another vital property of sulfonamides, which renders easier handling, purification, and characterization. Furthermore, sulfonamides are crucial catalysts in asymmetric synthesis.3 Moreover, tosylated derivatives are the reactive intermediates to synthesize various molecules including heterocycles containing N and O atoms.4Thus, discovering original routes for their synthesis is essential.
Sulfonylation is also used as a protective method for OH and NH functionalities as it permits crystallization and the protecting group can beeffectively removed under placid conditions.5 Moreover, the 2,4-dinitrobenzenesulfonamides (dNBS) of various peptides and amino acids have received massive attention as they are extremely important synthetically6 and biologically.7 To date, the majority of these changes have been accomplished from sulfonyl chlorides and the consistent amines in the presence of inorganic/organic bases, which produces stoichiometric amounts of HCl.8 It is important to develop a method that acid-labile protecting groups can tolerate, due to the synthetic importance of sulfonamides of peptides and amino acids, as they can be used as the precursors for original chemoselective ligation (NCL).9 Besides, dNBS are of great significance as they are useful synthons for ureas, thioureas, and thioamides.10 They have recently drawn attention as anti-tuberculosis drugs as they act as pro-drugs for the in vivo generation of SO2in addition to their synthetic importance.11
An intensive literature survey for the HCl-free synthesis of sulfonamides showed that merely five such synthetic strategies have been revealed, that includes the methods in which the sulfonic acids have been activated as the corresponding 3-methylimidazolium triflates,12 pentafluorophenolates,13 sulfonyl benzotriazoles,14 p-nitrophenolate esters15 and trichlorophenolates.16 Still, all the previously stated methods need either tedious heating conditions, severe reagents like trifluoromethanesulfonic anhydride (Tf2O), or the use of harsh bases. Moreover, strong bases as lithium hexamethyldisilylamide (LHMDSA) or nBuLi are used for less nucleophilic aniline derivatives.
Therefore, it is important to evolve a method where the sulfonic acid moiety is activated and goes through amidation under ambient conditions such that there will be no HCl production; a method like that would be in harmony with all acid-labile groups and resins for Fmoc-based SPPS (Solid Phase Peptide Synthesis). A method was recently reported in which the sulfonic acid is activated as the corresponding N-hydroxybenzotriazole ester.17 On the other hand, this technique is limited because triazoles are explosive on heating, although it serves the purpose well.
Sulfonamides as potent therapies for disease
Since the revelation of the first sulfonamide antibiotic prontosil and its dynamic metabolite sulphanilamide 1the significance and assorted qualities of sulfonamide medications has developed, setting them at the leading edge of drug design.18Although at first they were used as antibiotics, they subsequently showed incorporate diuretic, antitumour, antithyroid, hypoglycaemic and protease inhibitory activity.