Revisiting the Passerini Reaction Mechanism: Existence of the Nitrilium, Organocatalysis of Its Formation, and Solvent Effect

The Passerini reaction mechanism is revisited using high-level DFT calculations. Contrary to the common belief, the nitrilium intermediate is found to be stable in solution and its formation is rate-determining. The present results point out that this step is catalyzed by a second carboxylic acid molecule, as the subsequent Mumm rearrangement is. The solvent effect on the reaction rate was investigated: In a protic solvent like methanol, hydrogen bonds are responsible of the increasing barrier of the rate-determining step, compared to the commonly used solvent, the dichloromethane.