Design, eco-friendly synthesis, spectroscopic characterization and DFT studies of fluorinated aryl sulfonyl-DMAP salts

This work describes an efficient synthesis of fluorinated sulfonylating reagents. This report is specially based on the design, synthesis and characterization of three fluoro substituted sulfonamide synthons. These regio-isomeric synthons could be useful to prepare various sulfonamides. In this synthesis, dimethyl amino pyridine (DMAP) and corresponding fluoro substituted phenyl sulfonyl chlorides as a synthon, cyclopentylmethyl ether as a solvent have been used to accomplish higher yields (up to 96%). The reagents can be prepared under mild reaction conditions: (i) synthons are novel which may probably contain some synthetic advantages (ii) reaction operate in mild reaction conditions (iii) synthons are commercially available, solid, and stable in nature. Spectroscopic analysis indicates common singlet peak in the 19F-NMR spectra around −113 ppm for three novel synthons. DFT results have shown that the ortho and para halo synthons are more stable than meta substituted synthon as the value of ΔEHOMO-LUMO was higher for the ortho and para substituted synthon. To evaluate the scalability, the methodology was tested for multi-gram scale reactions and the results had shown that the precipitate was higher with optimized reaction condition and stoichiometric ratios up to a 5 g scale of the sulfonyl chlorides. We have synthesized novel regio-isomeric sulfonyl synthons ([DMAP-o/m/p-FPhSO2]+Cl−) and these are predicted to act as useful reagents while synthesizing active sulfonamide derivatives with various biological properties.