Electrochemical Dehydration of Carboxamides to Their Nitriles

An efficient electrochemical strategy for the dehydration of carboxamides to their corresponding nitriles is reported. This method replaces conventional dehydrating reagents with a thiocyanate‐mediated electrochemical activation, providing a safer, milder, and more sustainable alternative. Under optimized conditions in an undivided cell, 18 examples of aromatic and aliphatic carboxamides were smoothly converted to the corresponding nitriles at ambient temperature in good‐to‐excellent yields (up to 84%). Hexafluoroisopropanol proved to be essential for reaction efficiency, while tetrabutylammonium thiocyanate acted as a redox mediator, as confirmed by cyclic voltammetry studies, which revealed an EC‐type‐mediated oxidation process. The method demonstrates broad functional‐group tolerance, including halogenated, methoxylated, and sterically hindered substrates, as well as complex molecules derived from pharmaceuticals and natural products. Importantly, the protocol was successfully scaled up eightfold with minimal loss in yield, illustrating its robustness and practical applicability. Mechanistically, anodic oxidation of thiocyanate generates highly reactive species that activate the amide functionality, leading to nitrile formation via an oxidative dehydration pathway, while hydrogen evolution occurs at the cathode. This work expands the synthetic utility of electrochemical dehydration reactions and offers a valuable, environmentally responsible route to nitrile‐containing compounds of broad relevance for pharmaceuticals, agrochemicals, and materials science.