TEMPO‐Mediated Electrochemical N‐demethylation of Opiate Alkaloids
Ali Alipour Najmi, Mohammad Faizan Bhat, Rainer Bischoff, Gerrit J. Poelarends, Hjalmar P. Permentier
Abstract
Abstract A new TEMPO‐mediated electrochemical method has been developed for N‐demethylation of opiates using a home‐made batch cell with low‐cost porous glassy carbon electrodes. N‐demethylation of opiates such as thebaine, codeine, morphine and oxycodone is a key step in the semi‐synthesis of opioid medicines. The electrochemical N‐demethylation using TEMPO as mediator enables the synthesis of noropiates, which is not possible with conventional Shono oxidation. Electrolysis was performed at a preparative scale in aqueous solvent at room temperature in a single step, yielding the desired products in good isolated yields (up to 83 %). Mechanistic studies suggest that the electrochemically generated oxoammonium species oxidizes the opiate to an iminium intermediate, which then hydrolyzes to the noropiate. The electrochemical reaction was also performed in a flow‐cell without a supporting electrolyte and represents the first electrochemical N‐demethylation of difficult opiates with an aminoxyl oxidant.