Theoretical study of the neutral hydrolysis of methyl formate via a concerted and stepwise water-assisted mechanism using free-energy curves and molecular dynamics simulation

Abstract

A procedure previously described by us is used for the theoretical study of chemical reactions in solution by means of molecular dynamics simulation, with solutesolvent interaction potentials LJ (12-6-1) derived from ab initio quantum calculations. We apply the procedure to the case of the neutral hydrolysis of methyl formate, HCOOCH 3 ? 3H 2 O ? HCOOH ? CH 3 OH ? 2H 2 O in aqueous solution, via concerted and stepwise water-assisted mechanisms. We use the solvent as reaction coordinate, and the free-energy curves for the calculation of the activation energies. The theoretical calculation for the thermodynamics of this hydrolysis reaction in aqueous solution, assisted by three water molecules, is in agreement with the available experimental information. In particular our study gives values of DG = = 28.88 and 28.17 kcal/mol for the concerted and stepwise mechanisms, close to the experimental activation barrier of 28.8 kcal/mol, and a significant improvement over the values of 48.05 and 45.66 kcal/mol found in another similar study using the PCM model.

Achieving an Order of Magnitude Speedup in Hybrid-Functional- and Plane-Wave-Based Ab Initio Molecular Dynamics: Applications to Proton-Transfer Reactions in Enzymes and in Solution

“…The hydrolysis of carboxylic esters is one of the well-studied reactions in the field of chemistry, biochemistry, and industrial chemistry. Methyl formate hydrolysis serves as the simplest model for the hydrolysis of carboxylic esters and has been well studied experimentally − and theoretically. − In our present work, we modeled the methyl formate hydrolysis reaction in neutral water. This reaction happens through proton-transfer between the solvent and the solute.…”

“…Neutral hydrolysis of methyl formate leads to the formation of formic acid and methanol. It follows a stepwise mechanism, where addition of a solvent water molecule to the carbonyl group results in a stable gem-diol intermediate (see Figure ), followed by the decomposition of the intermediate to the final products. , In our work, we focus only on the elementary step leading to the formation of the gem-diol intermediate. The free energetics for this reaction step was computed using the WS-MTD technique.…”

“…We also note in passing that the previous computational studies have reported a range of free energy barriers for this reaction at 298 K. Gunaydin and Houk reported that autoionization of water is the rate-determining step and the free-energy barrier was predicted to be 23.8 kcal mol –1 (which in turn was taken from experiment data). Tolosa Arroyo et al reported a free-energy barrier of 28.17 kcal mol –1 based on their MD simulations using empirical potentials.…”

Understanding the Hydrolysis Mechanism of Ethyl Acetate Catalyzed by an Aqueous Molybdocene: A Computational Chemistry Investigation

“…Because some steps involve hydrogen shifts and water additions, a discrete–continuum solvent model was also used in order to obtain a more realistic description of the process and of the implied energy barriers. Previous theoretical studies on ester hydrolysis in the absence − and in the presence of metal complexes , as well as those for nitrile hydration catalyzed by aqueous molybdocenes and Pd(II) complexes have shown the adequacy of including explicit water molecules to simulate the most significant features in the rearrangements mentioned above. On the basis of these investigations, we have considered the minimum number of essential water molecules (two explicit water molecules) to reproduce the main features involved in the hydrogen shift and water addition processes found in the present work.…”

“…The aqueous hydrolysis of ethyl acetate is commonly used as a representative procedure for the theoretical study of the hydrolysis of carboxylic acid esters. While the hydrolysis mechanism of this and other esters has theoretically been investigated in considerable detail in the absence of metal complexes, − theoretical works are scarce for organometallic catalysts and practically null for aqueous molybdocene catalysis. , From an experimental point of view, four mechanisms have been considered to account for the hydrolysis of ethyl acetate catalyzed by [Cp′ 2 Mo(OH)(OH 2 )] + (Cp′ = η 5 -C 5 H 4 CH 3 ): , the intramolecular nucleophilic attack, the general base catalysis, the Lewis acid coordination assisted mechanism, and the intermolecular nucleophilic attack (see Scheme ). In the first three proposals the ester bonds to the metal, while in the last one a water ligand saturates Mo coordination and the ester does not coordinate to the metal.…”