(112b) Solvent Effects On a Menschutkin Reaction: Experiments, DFT Calculations and Optimal Solvent Design

Most industrial liquid-phase reactions take place in solution. It is known that the solvent can play a determining role to the outcome of the reaction, and that selecting an optimal solvent for a given reaction is crucial. Most of the time, however, the choice of solvent is based on experience, insight and limited heuristics. A desirable goal would be to predict how solvents behave with respect to selected reaction indicators, such as rate of reaction, yield and selectivity. We present a study comparing theoretical rate constants with experimental data for a Menschutkin reaction involving pyridine and phenacyl bromide as the reactants (Barnard and Smith 1981). We then show how this information can be used to identify optimal solvents for this reaction.

The computed rate constants are obtained from quantum mechanical transition-state calculations, using density functional theory to compute the free energy barrier associated with the formation of the activated complex. We use the continuum solvation model IEF-PCM (Tomasi et al. 1999) at the B3LYP/6-31+G* level of theory. The range of solvents chosen is based on their dielectric constant values. Specifically, we investigate: toluene, ethyl acetate, chorobenzene, aniline, tetrahydrofuran, dichloromethane, methanol, nitromethane and DMSO. This theoretical data are contrasted with measured reaction rate constants obtained from solution calorimetry experiments . The reactants were added in different excesses and the heat of reaction measured and subsequently subtracted from the calorimetry measurements to identify the rate of reaction constant. Nitromethane is identified as the best solvent from the experimental set, whereas DMSO and aniline react with the reactants.

The information obtained is then used as the basis for a computer-aided molecular design problem (CAMD) in which the structure of the solvent molecule is optimised to achieve the maximum rate of reaction. This allows solvents outside of the experimental set to be assessed in silico and therefore serves as a guide to further experimentation.

References

Barnard, P. and Smith, B. (1981), ?The Menschutkin Reaction: A group experiment in a kinetic study', Journal of Chemical Education 58(3), 282?285.

Blackmond, D. G. (2005), ?Reaction progress kinetic analysis: A powerful methodology for mechanistic studies of complex catalytic reactions', Angewandte Chemie- International Edition 44(28), 4302-4320.

Tomasi, J., Mennucci, B., Cancès, E. (1999), ?The IEF version of the PCM solvation method : an overview of a new method addressed to study molecular solutes at the QM ab initio level', Journal of Molecular Structure 464, 211-226.