Mechanism of aromatic nucleophilic substitution

The SiiAr2 mechanism of aromatic nucleophilic substitution is theoretically sound and based on experimental evidence, the most decisive of which involves carbocyclic compounds. Strong support for the mechanism has been published by Bunnett and Randall, in particular, the nature of the base-catalysis of the reaction of... 

The SifAr2 Mechanism in Azines The theoretical objections to the synchronous, one-stage bimole-cular mechanism of aromatic nucleophilic substitution are reviewed in Section I,C,4. The two-stage mechanism is illustrated by the... 

Mechanism of aromatic nucleophilic substitution. The reaction occurs in two steps and involves a resonance-stabilized carbanion intermediate. 

The synchronous bimolecular mechanism for aromatic nucleophilic substitution involves unfavorable geometry (bonds made and broken are both in the plane of the ring and backside attack is not possible) and unfavorable energetics (one high-energy step is required... 

There are four principal mechanisms for aromatic nucleophilic substitution. Each of the four is similar to one of the aliphatic nucleophilic substitution mechanisms discussed in Chapter 10. 

The basic concepts of nucleophilic substitution reactions appeared in the first semester of organic chemistry. These reactions follow or Sp 2 mechanisms. (In aromatic nucleophilic substitution mechanism, we use the designation Sp Ar.) In Sfjl and Sp 2 mechanisms, a nucleophile attacks the organic species and substitutes for a leaving group. In aromatic systems, the same concepts remain applicable, but with some differences that result from the inherent stability of aromatic systems. 

By far the most important mechanism for aromatic nucleophilic substitution consists of two steps ... 

Revision of aromatic nucleophilic substitution and a chance to unravel an interesting mechan -... 

There have been a large number of detailed studies, especially involving kinetic measurements, that have helped to determine the reactivity of various nucleophiles, solvent effects, and the finer details of aromatic nucleophilic substitutions proceeding via the addition-elimination mechanism. We will not attempt to summarize these results here, since reviews are available. Carbanions, alkoxides, and amines are all reactive in nucleophflic aromatic substitution and provide most of the cases in which this reaction has been used preparatively. Some examples are given in Scheme 7.7. 

Kinetic studies have shown that the enolate and phosphorus nucleophiles all react at about the same rate. This suggests that the only step directly involving the nucleophile (step 2 of the propagation sequence) occurs at essentially the diffusion-controlled rate so that there is little selectivity among the individual nucleophiles. The synthetic potential of the reaction lies in the fact that other substituents which activate the halide to substitution are not required in this reaction, in contrast to aromatic nucleophilic substitution which proceeds by an addition-elimination mechanism (see Seetion 10.5). 

It is quite reasonable to expect the bimolecular two-stage mechanism Sj Ar ) to predominate in most aromatic nucleophilic substitutions of activated substrates. However, only in rare instances is there adequate evidence to rule out the simultaneous occurrence or predominance of other mechanisms. The true significance of the alternative mechanisms in azines needs to be determined by trapping the intermediates or by applying modem separation and characterization methods to the identification of at least the major portion of the products, especially in kinetic studies. 

The lack of a uniform order of relative reactivity of the halogens in reactions of certain nucleophiles with nitro- and polynitro-phenyl halides led Parker and Read to propose a one-stage mechanism for some aromatic nucleophilic substitutions. An alternative explanation within the framework of the two-stage S Ar2 mechanism had been proposed earlier. A range of mechanisms has been considered in the past by Chapman, who properly points out that only in a limited number of examples is the evidence for the two-stage mechanism compelling even though the balance of evidence favors it. 

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