Solvent effects on methyl transfer reactions. 2. The reaction of amines with trimethylsulfonium salts

The reaction of ammonia and pyridine with trimethylsulfonium ion has been s tudied in gas phase and solution. Density functional theory at the B3LYP/6- 311-G* level was used to describe the energy changes along the reaction coo rdinate in the gas phase, and the self-consistent isodensity polarizable co ntinuum model (SCI-PCM) was used to calculate the effect of cyclohexane and dimethyl sulfoxide as the solvent on the energy changes. The effect of wat er as the solvent was studied using the Monte Carlo free energy perturbatio n method. The reaction with both ammonia and pyridine follows a similar rat her convoluted path in gas phase, with the formation of several reaction co mplexes before and after the formation of the transition state. All the spe cies found in gas phase persist in cyclohexane, yielding a reaction path ve ry similar to that in gas phase but with significant differences in the rel ative energy of the critical points. In DMSO, the energy profile is greatly simplified by the disappearance of several of the species found in gas pha se and in cyclohexane. The activation free energy increases with the polari ty of the solvent in both reactions. Increasing the polarity of the solvent also increases the exothermicity of the reaction of trimethylsulfonium ion with ammonia and reduces it in the reaction with pyridine. In water, the f ree energy profile follows the same trend as found for DMSO, and free energ y of activation is calculated to be larger by about 2-3 kcal/mol. This is i n good agreement with an experimental measurement of the effect of solvent on the rate of reaction.