The SN mechanism in aromatic compounds. XXXVII. Reactivity of amines

Abstract

A semi-empirical theoretical procedure utilizing bond-dissociation, solvation, and ionization energies as the main terms is used to calculate reactivity of amines, which constitute the main class of neutral nucleophiles, with some typical neutral aromatic substrates in protic solvents; and their reverse, i.e. reactivity of anionic nucleophiles with cationic (ammonio) substrates. The procedure has previously been used successfully to calculate reactivity of anionic nucleophiles with neutral substrates. In each class the calculations also lead to estimates of other important parameters such as leaving group mobility. The procedure is applicable in principle to reactions of nucleophiles with other organic and with inorganic substrates and to reactions in aprotic solvents.     In this paper, the procedure is applied to some representative reactions of amines with neutral aromatic substrates in protic solvents and predicts, in accordance with experimental data where available, (i) reactivity in the order: NH₃ < MeNH₂ < Me₂NH > Me₃N; PhNH₂ > PhNHMe > PhNMe₂; MeNR₂ > PhNR₂ (R = H or Me); (ii) leaving group mobility in the order: F > Cl (and other heavy halogens) in the reactions of aliphatic amines and aniline; F > Cl in the reactions of N-methylaniline; and F < Cl in the reactions of N,N-dimethylaniline; (iii) small values of ΔE? ( ≈ ΔH? in solution reactions). Small values of log B (very negative values of ΔS?) are predictable on general theoretical grounds, and these are modified by steric factors.     Similar amine reactivity patterns are common with non-aromatic substrates, and the explanations given by the procedure are of general application, apart from differences in the steric factors.