Nucleophilic Substitution in Solution: Activation Strain Analysis of Weak and Strong Solvent Effects

We have quantum chemically studied the effect of various polar and apolar solvents on the shape of the potential energy surface (PES) of a diverse collection of archetypal nucleophilic substitution reactions at carbon, silicon, phosphorus, and arsenic by using density functional theory at the OLYP/TZ2P level. In the gas phase, all our model S_N2 reactions have single-well PESs, except for the nucleophilic substitution reaction at carbon (S_N2@C), which has a double-well energy profile. The presence of the solvent can have a significant effect on the shape of the PES and, thus, on the nature of the S_N2 process. Solvation energies, charges on the nucleophile or leaving group, and structural features are compared for the various S_N2 reactions in a spectrum of solvents. We demonstrate how solvation can change the shape of the PES, depending not only on the polarity of the solvent, but also on how the charge is distributed over the interacting molecular moieties during different stages of the reaction. In the case of a nucleophilic substitution at three-coordinate phosphorus, the reaction can be made to proceed through a single-well [no transition state (TS)], bimodal barrier (two TSs), and then through a unimodal transition state (one TS) simply by increasing the polarity of the solvent.