The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution

In contrast to nucleophilic substitution in alkyl halides, where alkyl fluorides are exceedingly unreactive, aryl fluorides undergo nucleophilic substitution readily when the ring bears an o- or a p-nitro group. 

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the 

Relative reactivity toward sodium methoxide in methanol (50°C)  

Kinetic studies of these reactions reveal that they follow a second-order rate law Rate = [Aryl halide] [Nucleophile] 

Second-order kinetics is usually interpreted in terms of a bimolecular rate-determining step. In this case, then, we look for a mechanism in which both the aryl halide and the nucleophile are involved in the slowest step. Such a mechanism is described in the following section. 

21 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution 

Nucleophilic substitution, with inversion of configuration, is blocked by the benzene ring of an aryl halide. 

The generally accepted mechanism for nucleophilic aromatic substitution in nitro-substituted aryl halides, illustrated for the reaction of p-fluoronitrobenzene with sodium meth-oxide, is outlined in Mechanism 12.6. It is a two-step addition-elimination mechanism, in which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group. The mechanism is consistent with the following experimental observations  

Kinetics Consistent with the observed second-order rate law, the rate-determining step (step 1) involves both the aryl halide and the nucleophile. 

This mechanism is sometimes called N Ar substitution-nucleophilic-aromatic). 

Most stable contributing structure negative charge is on oxygen 

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THE ADDITION-ELIMINATION MECHANISM OF NUCLEOPHILIC AROMATIC SUBSTITUTION... 

The reaction of benzenesulfonic acid with sodium hydroxide (first entry in Table 24.3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 23.6). Hydroxide replaces sulfite ion (S03 ) at the carbon atom that bear s the leaving group. Thus, p-toluenesulfonic acid is converted exclusively to p-cresol by an analogous reaction ... 

FIGURE 23.3 The addition-elimination mechanism of nucleophilic aromatic substitution. 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 12.21). 

Nucleophilic Aromatic Substitution 490 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution 492 Related Nucleophilic Aromatic Substitutions 494 12.22 Summary 496 Problems 500... 

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