Inductive effect of uncharged groups:: dependence on electronegativity

Substituent effects in rigid non-conjugated systems were followed on the series of 3-substituted 1-fluoro-bicyclo[1.1.1]pentanes and 2-substituted 1-fluoroethanes in the fixed ap conformation. Their energies were calculated within the framework of the density functional theory at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-311++G(3df,3pd) level and the substituent effects were expressed in terms of isodesmic homodesmotic reactions. The results were confirmed by the energies of 1,4-disubstituted bicyclo [2.2.2] octanes reported in the literature and calculated at a lower level. Interaction of two common substituents of low or medium polarity cannot be described as the classical inductive effect by one term, proportional in all series, but an additional parameter is necessary, which depends only on the first atom of the substituent and may be identified with its electronegativity. The second term decreases with the distance more steeply than the first term and is always much less important. Nevertheless its statistical significance was proved by several sensitive tests at the highest level used in statistics. When one of the substituents is charged (or at least strongly polar as NO2 or CN), the first term is much increased and the second becomes less significant or insignificant. Therefore, the standard definition of the inductive effect with a uniform, universally valid constant can be retained as far as one treats only the ionization equilibria, both in solution and in the gas phase, or kinetics with a strongly polar transition state. In contrast to the firm statistical proofs, the physical meaning of the electronegativity term was not established. Any relation to various group electronegativities does not exist, similarity to the C-13 NMR shifts is merely qualitative. Copyright (c) 2006 John Wiley & Sons, Ltd.