Electrochemical Synthesis of an N-Arylpyridazinone: Discovery and Scale-Up

An electrochemical NH/CH-coupling of a functionalized pyridazinone with veratrole was developed to create the central C-N bond of an agrochemical intermediate. Electrolysis was performed in methanol using potassium pivalate, which served a dual role as both a mild catalytic base and a supporting electrolyte; H2 is generated as the sole stoichiometric byproduct. Mechanistic studies suggest the formation of a N-centered radical on the pyridazinone nitrogen that adds to the veratrole pi-system; closure of the catalytic cycle involves further one-electron oxidation and deprotonation. Initial optimization in a batch electrochemical cell was followed by optimization of a loop-flow process that provided significant yield improvements from batch. The loop-flow electrochemical process was successfully scaled to a reaction volume of 2 L.