الفهرس 
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Abstract
Nucleophilic Aromatic Substitution Reactions SN Ar of Aryl Compounds:
For neutral nucleophiles (e.g. amines, alcohols, water) there is much evidence that the addition elimination mechanism depicted in Eq (1.1) fits very well most of the intermolecular and intramolecular nucleophilic displacements involving nitro-activated aromatic substrates.2
Some of the most important evidence for the two-step mechanism comes from studies of base catalysis in this regard, reactions involving primary and secondary amines have played a central role.2-6 The initially formed σ-adduct, 1.1, is zwitterionic and contains an acidic proton, which can be removed by a base which may be the nucleophile itself. Conversion of 1.1 to products can then occur via the uncatalysed k2 pathway or via the base-catalysed k3B pathway. The influence of Brønsted base catalysis, the experimental observation of 1,1- and 1,3-σ-adducts, the sensitivity of the system to medium effects, are some experimental evidence of the mechanism depicted in Eq (1.1)
Assuming for simplicity that only a particular base B is an effective catalyst in Eq (1.1), application of the steady-state approximation derives in Eq (1.2) the expression of the second-order rate constant kA, at a given concentration of B.
Eq (1.2)
Three main situations of interest with respect to the reaction shown in Eq (1.1) were earlier considered in Eq (1.2).3b
(a) k2 + k3B [B] >> k-1. In this case, no base catalysis is possible: Eq (1.2) simplifies to kA = k1 and the formation of the intermediate is rate-limiting.
k2 + k3B [B] << k-1. This situation corresponds to a rapid formation of the intermediate 1.1 followed by its rate-determining decomposition. In this case, Eq (1.2) reduces to Eq (1.3), which predicts base catalysis with a linear dependence of kA on [B]:
Eq (1.3)
(b) k2 + k3B [B] ≈ k-1. In this intermediate situation Eq (1.2) indicates that base catalysis should be observed with a curvilinear dependence of kA on [B]. At low [B] the plot of k vs [B] should be a straight line which will change to a plateau at high [B], where formation of the intermediate becomes rate-limiting. A downward curvature is expected on these grounds. Numerous kinetic studies devoted to the reactions shown in Eq (1.1) have demonstrated the validity of Eqs (1.2) and (1.3).3-11
The isolation and/or NMR spectroscopic characterization of σ-complexes have received considerable attention over the past two decades, become of the relationship between the formation of such adducts and that of the metastable cyclohexadienyl intermediates postulated in the SNAr mechanism. These studies constitute an important contribution to the understanding of the intermediate involved in SNAr, furthermore, most of the σ-adducts were formed by the addition of anionic nucleophiles.2a,6,12
Many recent investigations have been also carried out in the field of heterocyclic compounds. As a result of the replacement of a ring carbon atom in arene systems by a more electronegative atom, the greater electron density on that atom and the concomitant reduction in electron density on the remaining carbon atoms make these substrates prone to suffer nucleophilic attack. A 1H and 13C NMR study of substituted nitropyridines and nitrobenzene, and of their SNAr products obtained with amines, demonstrated that the electronic aza and nitro group effects are comparable if conjugation of the nitro group is not hindered.13 Many SNAr reactions with nitro- activated heterocyclic compounds have been reported; however, a peculiar feature of aza-aromatic systems is that nucleophilic displacements of common leaving groups, as well as of hydrogen, can occur through multistep sequences involving ring opening reclosure (RORC) of the hetero-cyclic system.14 These reactions are commonly referred to as SN(ANRORC) because they are promoted by initial addition of the nucleophile (AN) at an activated unsubstituted carbon.2a,14 The feasibility of nucleophilic substitutions at the 4- or 7- position in condensed heterocycles such as nitrobenzofurazans has been also recently proved, and the finding of σ-adducts of the type found in trinitrobenzene analogues gives strong support to the operation of similar mechanisms.15
Numerous kinetic studies devoted to SNAr reactions with amines indicate that the occurrence and efficiency of base catalysis depend on the identity of the amine, the nucleofugue, the base and the solvent. In general, base catalysis is more often observed with secondary than with primary amines, with poor leaving groups and in the less polar solvents; one of the three described kinetic situations is observed. Nevertheless, it will be shown in the forthcoming discussion that a new situation has been recently discovered: for several systems an upward curvature has been found in the plot of kA vs [B], which corresponds to a parabolic dependence of kA on [B], and a fourth-order kinetic law. Several alternative mechanisms have been proposed to account for this new kinetic finding. Most of the more relevant findings related to SNAr reactions in the last decade have been observed in aprotic solvents, and the factors that have been studied with amines in aprotic solvents will be discussed. The first part will deal with works where some of the three kinetic situations described above have been found. In the second part, the systems where ‘anomalous’ kinetics have been observed will be discussed.