Computational investigation of the effect of α-alkylation on SN2 reactivity: acid-catalyzed hydrolysis of alcohols

Computed potential energy barriers (HF, B3LYP and MP2/6-31G*; vacuum and PCM water) for simple SN2 identity reactions H2O + R–OH2+→+H2O–R + OH2 tend to decrease along the series R = Me, Et, Pri and But, in contrast with those calculated for Cl− + R–Cl→Cl–R + Cl−. The SN2 reaction profile for H2O + But–OH2+ shows a sequence of three steps, each with a transition structure corresponding to the internal rotation of a single methyl substituent. The same three rotations also appear in the SN2 reaction profile for Cl− + But–Cl, but as distinct stages of a concerted process with a single transition structure; only the second methyl group undergoes internal rotation in the transition vector itself. Simulation of reactions H2O + R–OH2+, using the AM1/COSMO method for treatment of aqueous solvation, illustrates the changing energy surface topography accompanying SN2/SN1 mechanistic changeover along the series R = Me, Et, Pri and But, and permits determination of kinetic isotope effects for both pathways with each alkyl group. Mechanistic change occurs by alteration of the relative energies of the TSs along these competing paths. Computational modelling allows investigation of experimentally unobserved reaction mechanisms, such as SN1 for primary substrates.