S _N Ar Reactions of Amines in Aprotic Solvents

Abstract

Introduction Systems Showing Classical Kinetics Systems Showing ‘Anomalous’ Kinetics Concluding Remarks Acknowledgements

Aromatic nucleophilic substitution in aprotic solvents using hydrogen‐bonded biological amines. Kinetic studies and quantum chemical calculations

“…Hirst's interpretation is common to dimer mechanism, reflecting different parts of a spectrum of methods for the formation of the intermediate. [6] For a given nucleophile, dimer formation increases with increases of concentration and hence increases the reaction rate as observed in the present study.…”

“…[4] Self-association of amines to form mainly dimers by H bonds is a long-known phenomenon, and there is abundant information in the literature about dimers that are responsible for the 'dimer nucleophile' mechanism when amines are used in ANS carried out in aprotic solvents. [5,6] Intermolecular hydrogen bonding increases the nucleophilicity of the dimer compared with the monomer, as confirmed by semi-empirical [45] and ab initio calculations. [24] On the other hand, when two amino groups are in a rigid appropriate geometry, strong intramolecular H bonding is easily established, and such compounds exhibit unusually high basicity.…”

“…For arginine, agmatine, lysine and dopamine, the second-order rate coefficients, k A , were found to increase rapidly with the amine concentration, The protonated dimer catalyses the nucleofuge departure in low-permittivity solvents. [6] For arginine and agmatine, the intercept in Fig. 3 is null, indicating that these reactions proceed fully by the 'dimer nucleophile' mechanism.…”

“…With chlorine as the nucleofuge, usually the first step is ratedetermining; nevertheless, a third-order-in-amine kinetic law was observed, as it has been recently reported using alicyclic diamines and polyamines that form intramolecular or intermolecular hydrogen bond in aprotic solvents. [6,8,20,21] As shown in Table 1, the reactions with histamine and 2-GB are the slower ones, reflecting the effects of sterically demanding polyamines for reacting with the substrate; in contrast, the flexible structure polyamines that form intermolecular homo-dimers have the nucleophilic atom more available and form stable dimers (see theoretical calculations), leading to faster reactions.…”

“…In 1,2diaminobenzene, intramolecular H bond prevents the intermolecular H-bonded dimer, while in the reactions carried out in aprotic-protic solvents, the formation of nucleophile/co-solvent, mixed aggregates prevents the H bond self-aggregation of the nucleophile, as we previously reported. [17][18][19] Preferential solvation can be responsible for dramatic changes in reaction mechanisms in ANS, as it has been shown experimentally [6,8,18] and recently confirmed by quantum chemical calculations. [1] Previous works reported by Hirst et al [50] proposed that the upward curving plots observed in ANS reactions carried out in aprotic solvents can be explained via cyclic transition state formation and electrophilic catalysis expulsion of the leaving group by homo-(or hetero)conjugated acid of the nucleophile by proton transfer from the intermediate.…”