Green electrochemical late-stage sulfonylation of clonazepam an anticonvulsant benzodiazepine drug.

The electrochemical synthesis of new benzodiazepine derivatives, via late-stage modification of clonazepam (CZP), a benzodiazepine anticonvulsant drug, is one of the two main objectives of this research. To achieve this goal, electrochemical oxidation of this drug was carried out in the presence of arylsulfinic acid derivatives (ASA) in an undivided cell equipped with a graphite anode and cathode, in a water/ethanol mixture, under controlled potential conditions. In this method, new benzodiazepines were synthesized under easy workup and environmentally friendly conditions without the need for catalysts, reagents, or toxic solvents, at room temperature and pressure. In another part of this research, the electrochemical behavior of CZP was thoroughly investigated and new information was reported on the electrochemical reaction mechanism, the major metabolite of CZP, and the relationship between potential and pH. The proposed mechanism for the late-stage modification of CZP involves the sequential reduction and oxidation of CZP at the cathode and anode, respectively, followed by reaction with the nucleophile (ASA). In addition, docking studies were performed on the synthesized compounds and it was found that the synthesized derivatives can interact well with the gamma-aminobutyric acid agonist (GABA).