The Meisenheimer model for predicting the principal site for nucleophilic substitution in aromatic perfluorocarbons — Generalization to include ring-nitrogen atoms and non-fluorine ring substituents

Abstract

Our recent simple model for predicting the principal site for nucleophilic substitution in aromatic perfluorocarbons (J. Fluorine Chem. 2005, 126, 727) is generalized to include both ring-nitrogen atoms and non-fluorine ring substituents. The model is based on the relative stabilities of the Meisenheimer complexes as calculated using Hartree–Fock theory with a modest basis set. Calculations on a wide range of fluorine-containing aromatics demonstrate the general applicability of the model; in over 70 systems examined, we found only one where the predicted primary substitution site did not agree with the experimental findings. We demonstrate that criticism by Chambers et al. to the effect that the model is incapable of reproducing experimental substitution patterns, and, in particular, cannot distinguish between the different activating effects of ortho- and para-fluorines, are entirely unfounded. The observed substitution patterns for six reactions involving attack by aniline on perfluoropyridine and various non-fluorine-substituted derivatives, selected by Chambers et al. to highlight the failings of our model, are, on the contrary, accurately predicted by it.