Small steric effects in isolated molecules: alkyl-substituted benzonitriles

A series of seven alkyl-substituted benzonitriles was investigated as a model for small steric effects (van der Waals tension) excluding any steric inhibition due to resonance. The energies were calculated at a B3LYP/6-311+G(d,p) level and the gas-phase basicities of some compounds were measured by Fourier-transform ion cyclotron resonance. Substituent effects were evaluated separately for neutral molecules and protonated forms by means of isodesmic reactions, and dissected into polar and steric effects by comparing ortho and para derivatives. One or two ortho methyl groups have a relatively small steric effect operating almost exclusively in the protonated form which leads to weakened basicity. An ortho tert-butyl group exerts a strong steric effect both in the protonated and nonprotonated forms, manifested also in a rather strong distortion of geometry. The effect on basicity is then a small difference of two large values and is base strengthening. Acid–base properties are in such cases a poor measure of substituent effects and cannot be interpreted in simple terms.