Solvent Effects on the Menshutkin Reaction

TL;DR

This study uses reactive molecular dynamics to explore how different solvents affect the energetics and mechanisms of the Menshutkin methyl transfer reaction, revealing solvent-dependent catalytic effects and structural dynamics.

Contribution

It provides detailed computational insights into solvent effects on the Menshutkin reaction, including barrier heights and solvent distribution changes during the reaction pathway.

Findings

Polar solvents catalyze the reaction more effectively.

Barrier heights closely match experimental data in key solvents.

Solvent distributions change significantly between reactant and transition states.

Abstract

The Menshutkin reaction is a methyl transfer reaction relevant in fields ranging from biochemistry to chemical synthesis. In the present work, energetics and solvent distributions for NH$_{3}$+MeCl and Pyr+MeBr reactions were investigated in the gas-phase, in water, methanol, acetonitrile, benzene, and in cyclohexane by means of reactive molecular dynamics simulations. For polar solvents (water, methanol, and acetonitrile) and benzene, strong to moderate catalytic effect for both reactions is found whereas apolar and bulky cyclohexane interacts weakly with the solute and does not show pronounced barrier reduction. Calculated barrier heights for the Pyr+MeBr reaction in acetonitrile and cyclohexane are 23.2 and 28.1 kcal/mol compared with experimentally measured barriers of 22.5 and 27.6 kcal/mol, respectively. The 2-dimensional solvent distributions change considerably between reactant and TS but comparatively little between TS and product conformations of the solute. The simulations also suggest that as the system approaches the transition state, correlated solvent motions that destabilize the solvent-solvent interactions are required to surmount the barrier. Finally, the average solvent-solvent interaction energies in the reactant, TS, and product state geometries are correlated with changes in the solvent structure around the solute.