Atomic-Level Mechanism, Solvent Effect, and Potential of the Mean Force of the F^– + CH₃CH₂Cl S_N2 Reaction in Aqueous Solution

Abstract

We investigate the bimolecular nucleophilic substitution (S N 2) reaction of F − with CH 3 CH 2 Cl in aqueous solution using combined multilevel quantum mechanism (ML-QM) theories with molecular mechanics (MM). The synchronized, atomic-level structural and charge evolutions are analyzed along the reaction path. The potential mean force along the reaction path in water is calculated at high-accuracy CCSD(T)/aug-cc-pVTZ/MM level of theory with a free energy barrier of 16.8 kcal/mol and a free energy of reaction of −9.7 kcal/mol. The water solvent hinders the reactivity by raising its reaction barrier by 15.1 kcal/ mol, of which 13.6 kcal/mol comes from solvent energy contribution and 1.5 kcal/ mol comes from the polarization effect. This indicates that the water solvent plays an essential role on this reaction in aqueous solution. We also predict the potential mean force profile based on the gas-phase reaction path and the solvation free energies of the stationary points; the comparison between our calculated result at CCSD(T)/ MM level shows an excellent agreement with the predicted one with the free energy barrier at 16.2 kcal/mol and the free energy of reaction at −8.3 kcal/mol.

Solvent-induced dual nucleophiles and the α-effect in the SN2 versus E2 competition

“…For nearly 50 years, the mechanism of the S N 2 reaction has been extensively studied experimentally and theoretically, including its temperature dependence, 1–3 benchmark studies, 4–11 steric effects, 12–21 and solvent effects. 14,15,22–29 Solvation can have a tremendous effect on chemical reactions. 14,15,22,30–32 Rate constants, for example, can be reduced by up to 16 orders of magnitude from the gas phase to aqueous solution.…”

Effects of Methyl Substitution and Leaving Group on E2/SN2 Competition for Reactions of F− with RY (R = CH3, C2H5, iC3H7, tC4H9; Y = Cl, I)

“…In this regard, theoretical approaches have played an important role in probing the mechanisms. Extensive theoretical investigations have mainly focused on the reactions of the type of X − + CH 3 CH 2 Y (X = F, Cl, OH, ClO, et al; Y = F, Cl, Br, I) over the years [13,14,16,17,[21][22][23][24][25][26][27][28][29]. The competition between E2 and S N 2 reaction pathways caused by multiple factors, such as nucleophile, leaving groups, substrate characteristics, and environment, has been investigated in detail [10,16,17,25,[28][29][30][31].…”