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

Abstract

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.

[Cp2Mo(OH)(OH2)]+‐Catalyzed Hydrolysis of Mono‐ and Difunctional Ethers: Theoretical Understanding of Their Divergent Reactivity

“…Recent in‐depth theoretical studies on the hydrolysis of ethyl acetate, the acrylonitrile hydration, and the carbon monoxide oxidation catalyzed by [Cp 2 Mo(OH)(OH 2 )] + have been valuable to corroborate and rationalize the experimental belief that the intramolecular nucleophilic attack of the hydroxo ligand on the Mo‐coordinated substrate is the operative mechanism (see Scheme ) , , . In accordance with experimental suggestions,, this mechanism begins with the replacement of the aqua ligand of the catalytically active complex [Cp 2 Mo(OH)(OH 2 )] + by the substrate (XY in Scheme ).…”

“…More interestingly, those theoretical results have also shown that the rate‐determining step of this kind of organometallic processes depends on the organic substrate considered. Specifically, the attack of the hydroxo ligand is the most energy‐demanding step for the substrates acrylonitrile and carbon monoxide , . Kinetic trends found experimentally for the hydration of several nitriles could be satisfactorily rationalized from that theoretical fact .…”

“…Specifically, the attack of the hydroxo ligand is the most energy‐demanding step for the substrates acrylonitrile and carbon monoxide , . Kinetic trends found experimentally for the hydration of several nitriles could be satisfactorily rationalized from that theoretical fact . However, in case of the hydrolysis of the ethyl acetate substrate, the ethanol release from the metallacycle intermediate formed just after the attack of the hydroxo ligand competes with the acetic acid formation to be the rate‐determining step.…”

A Theoretical Investigation on the Oxidation of Carbon Monoxide by an Aqueous Molybdocene

“…As only the product complex in this scheme could be experimentally detected, we also explored the alternative mechanism of general base catalysis, in which an external water molecule, which directly interacts with the hydroxide ligand, acts as a nucleophile for the attack on the Mo‐coordinated CO carbon atom. However, by taking into account experimental findings12,17,18 and our recent theoretical study on [Cp 2 Mo(OH)(OH 2 )] + ‐catalyzed nitrile hydration,40 we discarded other less likely mechanistic possibilities such as the attack of an external water molecule, which does not directly interact with the OH ligand, on the bound CO carbon atom.…”

“…26 kcal mol –1 )50 and more recently in the nitrile hydration catalyzed by [Cp 2 Mo(OH)(OH 2 )] + (ca. 15 kcal mol –1 ) 40. Finally, we also checked the effect of one explicit water molecule on TS3–R2_b along R2.…”