Electrochemically promoted annulation of aldehydes and carbazates: access to 2-alkoxy/aryloxy-5-substituted 1,3,4-oxadiazole and 1,3,4-oxadiazol-2(3H)-one derivatives

Abstract

An efficient and eco-friendly synthesis of chemically and pharmaceutically interesting 2-alkoxy/aryloxy-1,3,4-oxadiazoles, and 1,3,4-oxadiazol-2(3H)-ones has been developed through the annulation of aldehydes and carbazates. The protocol involves electrochemically promoted access to the desired products in good to excellent yields. The method uses NaBr as an electrocatalyst, and MeOH as a solvent. The strategy is oxidant-free and transition-metal free, offering the electrolyte-free completion of the reaction at room temperature. A possible mechanism has been proposed based on control-experiment results and literature reports. The practical utility of this approach is highlighted via the brief synthesis of 5-(4-chloro-3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2(3H)-one, which is a potent inhibitor of Notum carboxylesterase activity.