On the Mechanism of the [Cp₂Mo(OH)(OH₂)]⁺-Catalyzed Nitrile Hydration to Amides: A Theoretical Study

Nitrile hydration to amides catalyzed by [Cp₂Mo­(OH)­(OH₂)]⁺ has been theoretically investigated by using acrylonitrile as a model and performing density functional theory calculations (B3LYP), both in the gas phase and in water solution. In both media, our results confirm the experimental belief that, among four plausible proposals, the intramolecular nucleophilic mechanism is the most favored for this kind of process. A hydrogen migration from oxygen to nitrogen atoms is the rate-limiting step in the gas phase. In the continuum solvation model the most significant energy barriers become larger than in the gas phase due to the relatively large solvation of the [Cp₂Mo­(OH)]⁺ complex, which is taken as reference to measure such barriers. However, the inclusion of explicit water molecules in the hydrogen migration between oxygen and nitrogen atoms notably stabilizes this step; thus the attack of the catalyst hydroxide to the nitrile becomes the rate-limiting step in water solution with a Gibbs energy barrier of 33.8 kcal/mol, in agreement with the slow reaction rate experimentally observed. The replacement of acrylonitrile by lactonitrile, isobutyronitrile, acetonitrile, propionitrile, and 3-hydroxypropionitrile also gives rise to rate-determining Gibbs energy barriers in water solution consistent with experimental trends for the effect of electron-withdrawing substituents and for the effect of enlargement of the backbone of the nitrile, thus corroborating the reaction mechanism found for the title hydration process investigated.