A solvent-free mechanochemical electrophilic C–H thiocyanation of indoles and imidazo[1,2-a]pyridines using a cost-effective combination of N-chlorosuccinimide-NaSCN and tandem C–C and C–S bond formation

Abstract

Herein, we report a solvent-free and sustainable methodology for the electrophilic C–H thiocyanation of indoles and imidazo[1,2-a]pyridines in a mixer-mill. A combination of commercially available and cheaper precursors N-chlorosuccinimide and NaSCN was used under milling conditions for the in situ generation of N-thiocyanatosuccinimide (NTS) which facilitates the C-3 selective thiocyanation reaction on indoles and imidazo[1,2-a]pyridines. A series of thiocyanated products containing electron-rich and electron-deficient rings were synthesized in silica gel as the solid reaction media and good to excellent yields were obtained. The scalability of the reaction was validated with selected substrates at the gram scale. Moreover, we explored mechanochemical tandem C–C and C–S bond formation reactions by double C–H activation, leading to easy access to C-2 aryl and C-3 thiocyanato compounds from unsubstituted indoles. In addition, mechanochemical conversion of the –SCN precursors into –SCF₃ and 5-substituted sulfenyl tetrazole was also demonstrated in the current methodology.