A Comprehensive Mechanism for Aromatic Nucleophilic Substitution in Aprotic Solvents: Derivation of the Whole Reaction Scheme for Third Order in Amine Kinetic Law

摘要

When aromatic nucleophilic substitutions (ANS) with amines are carried out in solvents of low permittivity, a third order in amine kinetic law is often determined. Initially considered an “atypical” behavior, this and other peculiar findings could be consistently accommodated in a new mechanism for ANS that we called the “dimer nucleophile” mechanism. At present, there are abundant studies in the current literature where the “dimer” mechanism has been observed. Though most of the reported 4^th order ANS occurred with poor nucleophiles, we recently designed special systems that allowed the “dimer” mechanism be observed also with substrates where the first step is rate determining. In the present paper, the kinetic behavior and reactivity for ANS reactions performed with halonitrobenzenes and several bi- and poly-functionalized amines in toluene is reported. Special systems implying nucleophiles of flexible structure and appropriate rigid molecular geometry, regarding their hydrogen bond self-aggregation states were designed; the presence of non-nucleophilic hydrogen bond acceptor additives was also studied. It is shown that the nature of non-covalent weak interactions developed in aprotic media alter the properties of the nucleophile. Our results confirm that the association of amines in aprotic solvents plays an important role in defining the ANS mechanisms. An overall reaction Scheme is presented herewith, including determination of the partial k’s of the individual steps in the complex reaction.