Unraveling the Reaction Mechanism on Nitrile Hydration Catalyzed by [Pd(OH₂)₄]²⁺: Insights from Theory

Density functional theory methodologies combined with continuum and discrete-continuum descriptions of solvent effects were used to investigate the [Pd­(OH₂)₄]²⁺-catalyzed acrylonitrile hydration to yield acrylamide. According to our results, the intramolecular hydroxide attack mechanism and the external addition mechanism of a water molecule with rate-determining Gibbs energy barriers in water solution of 27.6 and 28.3 kcal/mol, respectively, are the most favored. The experimental kinetic constants of the hydration started by hydroxide, k(OH), and water, k(H₂O), attacks for the cis-[Pd­(en)­(OH₂)₂]²⁺-catalyzed dichloroacetonitrile hydration rendered Gibbs energy barriers whose energy difference, 0.7 kcal/mol, is the same as that obtained in the present study. Our investigation reveals the nonexistence of the internal attack of a water ligand for Pd-catalyzed nitrile hydration. At the low pHs used experimentally, the equilibrium between [Pd­(OH₂)₃(nitrile)]²⁺ and [Pd­(OH₂)₂(OH)­(nitrile)]⁺ is completely displaced to [Pd­(OH₂)₃(nitrile)]²⁺. Experimental studies in these conditions stated that water acts as a nucleophile, but they could not distinguish whether it was a water ligand, an external water molecule, or a combination of both possibilities. Our theoretical explorations clearly indicate that the external water mechanism becomes the only operative one at low pHs. On the basis of this mechanistic proposal it is also possible to ascribe an ¹H NMR signal experimentally detected to the presence of a unidentate iminol intermediate and to explain the influence of nitrile concentration reported experimentally for nitriles other than acrylonitrile in the presence of aqua–Pd­(II) complexes. Therefore, our theoretical point of view on the mechanism of nitrile hydration catalyzed by aqua–Pd­(II) complexes can shed light on these relevant processes at a molecular level as well as afford valuable information that can help in designing new catalysts in milder and more efficient conditions.