Microhydration effects on a model SN2 reaction in a nonpolar solvent

Abstract

Using a recently developed empirical valence bond model for the nucleophilic substitution reaction (S(N)2) in solution, we examine microhydration effects on the benchmark Cl(-) + CH(3)Cl reaction in liquid chloroform. Specifically, the effect of the hydration of the reactive system by one to five water molecules on the reaction-free energy profile and the rate constant is examined. We find that the activation-free energy is highly sensitive to the number of water molecules hydrating the nucleophile, increasing the barrier by about 4 kcal/mol by the first water molecule. With five water molecules, the barrier height is 10 kcal/mol larger than the barrier in bulk chloroform and only 3 kcal/mol below the barrier in bulk water. A number of properties vary monotonically with the number of water molecules, including the rate of change in the system's electronic structure and the solvent stabilization of the transition state. These and other properties are a rapidly varying function of the reaction coordinate. Deviation from transition state theory due to barrier recrossing is not large and falls between the behavior in bulk water and bulk chloroform.

Structure and Dynamics of Host/Guest Complexation at the Liquid/Liquid Interface: Implications for Inverse Phase Transfer Catalysis

“…The data described above and our previous MD studies of a model S N 2 reaction at interfaces , suggest that the presence (or absence) of water and β-CD hydroxyl groups in the vicinity of the αC should have a large impact on the reaction barrier. The precise locations of the reactive site relative to the β-CD molecule and surrounding water molecules in the IPTC system is helpful for quantifying the β-CD catalyst’s potential enhancement of the S N 2 reaction rate.…”

“…Previous studies of a model S N 2 reaction in solvents of varying polarity, at the water/organic interface, and in the case of microhydration (one to five water molecules near the reactive site) revealed that the S N 2 reaction center is very sensitive to the presence of water. If the β-CD/1-bromooctane complex effectively “dehydrates” the reaction site, the reaction rate should increase.…”

Radiofluorination of diaryliodonium tosylates under aqueous–organic and cryptand-free conditions

“…We previously determined the Arrhenius activation energy for the reaction of [ 18 F]fluoride ion with (2-methylphenyl)(phenyl)iodonium chloride in DMF-0.25% H 2 O medium and obtained a value of 18.3 kcal/mol [18]. Microhydration of chloride ion by as few as five water molecules has been calculated to increase the activation energy for reaction with chloromethane in chloroform by 10 kcal/mol [39]. A similar influence of microhydration of fluoride ion on its nucleophilicity may be reasonably expected, as evidenced by the effect of hydration of fluoride ion on rates of reaction with 4-chlorobenzonitrile [31].…”

Reaction Dynamics at Liquid Interfaces

“…For example, at Z = 15Å, ΔA* = 22 kcal/mol, which is similar to ΔA* = 21 kcal/mol calculated for the reaction in bulk chloroform with n = 1. As n increases, the activation free energy increases monotonically to the value in bulk water (147). However, when the reactants are near the Gibbs surface another effect is at play, which is related to the dependence of the reaction barrier on the reactants' orientation (142).…”