Steric effects in isolated molecules:: Gas-phase basicity of methyl-substituted acetophenones

The energies of 14 methyl-substituted acetophenones and of their protonated forms were calculated within the framework of the density functional theory at the B3LYP/6-311+G(d,p) level. The gas-phase basicities of some members of this series were measured using Fourier transform ion cyclotron resonance mass spectrometry in order to complete the known data. The protonated forms exist in two configurations differing in the position of the hydrogen atom; their equilibrium depends strongly on the substitution pattern. Taking into account all conformational equilibria, the experimental and calculated basicities agreed to within 2.7 kJmol(-1). Substituent effects were tentatively resolved into polar and steric contributions by comparing the corresponding ortho and para derivatives. The steric effect of the ortho-methyl groups defined in this way has a clear physical meaning proven by several correlations; it destabilizes the neutral acetophenone molecules but destabilizes the cations even more. Hence it is base-weakening relative to the steric effect on the acidity of substituted benzoic acids, which is acid-strengthening. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).