Scope and limitation of the inductive effect:: importance of charged substituents

The interaction of two relatively distant charged or dipolar groups was evaluated on 1,4-disubstituted bicyclo[2.2.2] octane derivatives as the reaction energy of the isodesmic-homodesmotic reaction, in which this derivative is formed from two mono derivatives. Energies of the individual compounds were calculated at the B3LYP/ 6-311+G(d,p) level. All combinations of 12 common substituents were investigated, representing 78 reaction energies in a 12 x 12 data matrix. The behaviour of charged and dipolar substituents is considerably different. Interaction with a charged group is described precisely (R > 0.997) by one parameter, essentially identical with the standard inductive constant sigma(1). Interaction of two dipolar substituents depends also on sigma(1), but requires an additional parameter, important particularly in the case of donor substituents (NH2, OH, Cl), less important to insignificant with the others. It is significantly correlated with the electronegativity of the first atom. Alternatively, it can be evaluated as a new parameter characterizing the substituent effect, say a new scale of group electronegativity different from the suggested scales. With two parameters, the interaction of polar substituents is expressed with similar high precision R > 0.99) as with charged substituents and one parameter. Copyright (C) 2004 John Wiley Sons, Ltd.