C-5 selective chlorination of 8-aminoquinoline amides using dichloromethane

An oxidant-free electrochemical regioselective chlorination of 8-aminoquinoline amides at ambient temperature in batch and continuous-flow was achieved. Inert DCM was used as the chlorinating reagent. Owing to the continuous-flow setup, the reaction scale up can be achieved conveniently with higher productivity. Moreover, this method has good position-control, and water and air tolerance. Costly quaternary ammonium salts were avoided. Radical-trapping, H/D exchange, KIE and cyclic voltammetry experiments were conducted to gain insight into the reaction mechanism.