Continuous N-Hydroxyphthalimide (NHPI)-Mediated Electrochemical Aerobic Oxidation of Benzylic C-H Bonds.

Abstract

Electroorganic chemistry has emerged as an environmentally benign tool for synthetic chemists to achieve efficient transformations that are challenging with traditional reagent-based methods. Continuous flow chemistry brings pharmaceutical industry numerous advantages, but implementing electroorganic synthesis in flow is challenging, especially for electroorganic reactions with coupled electrode reactions and slow chemical reactions. We present a continuous electrolysis system engineered for N-hydroxyphthalimide (NHPI) mediated electrochemical aerobic oxidation of benzylic C-H bonds. First, a cation-exchange membrane prevents the crossover of the NHPI anion from anolyte to catholyte avoiding reductive decomposition of NHPI at the cathode, and enables the usage of a cost-effective reticulated vitreous carbon (RVC) cathode instead of a platinum electrode. Second, running the electrochemical flow cell with recycle streams accommodates the inherently slow kinetics of the chemical reaction without phthalimide-N-oxyl (PINO) radical self-decomposition at the anode, and allows the usage of gaseous oxygen as co-oxidant.