ALKYLATION OF SUBSTITUTED SULFONAMIDES WITH BENZOTRICHLORIDE AND IPSO-SUBSTITUTION OF THE p-TOLUENESULFONAMIDE GROUP WITH NUCLEOPHILIC REAGENTS
DOI:
https://doi.org/10.15421/jchemtech.v33i3.332919Keywords:
sulfonamides, N-alkylation, benzotrichloride, ipso-substitution, aluminum chloride (AlCl₃), electrophilic catalysis, amines, pharmaceutical chemistryAbstract
Substituted alkyl and aryl sulfonamides have attracted increasing research interest due to their distinctive chemical reactivity. In particular, the arylsulfonyl moiety functions as an excellent leaving group (hypernucleofuge), making these compounds highly electrophilic and suitable for various aromatic substitution and transfer reactions. In this study, we explored the alkylation of substituted sulfonamides using polyhaloalkanes such as benzotrichloride. This reaction yielded imidoyl chlorides, which are important intermediates in the synthesis of natural products, pharmaceuticals, biologically active compounds, and advanced materials. Additionally, under specific conditions - including the presence of AlCl₃, 1,2-dichloroethane, and strong amines - we observed the replacement of the sulfonamide group by an amine via ipso-substitution. We investigated the synthesized compounds using infrared (IR) and nuclear magnetic resonance (NMR 1Н) spectroscopy, thin-layer chromatography (TLC) and elemental analysis. These techniques confirmed the structures and purity of the reaction products. Alkylation proceeded efficiently only in the presence of benzotrichloride and AlCl₃; other polyhalogenated reagents and Lewis’s acids exhibited no reactivity under comparable conditions. Furthermore, ipso-substitution of the sulfonamide group by strong nucleophilic amines (pKa > 10), such as dimethylamine and piperidine, occurred even in the absence of benzotrichloride. A nitro group in the para position of the arylamine moiety was essential for selective ipso-substitution, due to its activating effect on the aromatic system. Both electronic and steric factors were found to significantly influence the reaction pathway. Substituting the nitro group with other electron-withdrawing groups or placing it in non-para-positions significantly reduced the rate of the substitution process.
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