Addition-elimination mechanism for nucleophilic aromatic substitution

The product of this reaction as its sodium salt is called a Meisenheimer complex after the Ger man chemist Jacob Meisenheimer who reported on their formation and reactions in 1902 A Meisenheimer complex corresponds to the product of the nucleophilic addition stage in the addition-elimination mechanism for nucleophilic aromatic substitution... 

The addition-elimination mechanism for nucleophilic aromatic substitution requires strong electron-withdrawing substituents on the aromatic ring. Under extreme conditions, however, unactivated halobenzenes react with strong bases. For example, a commercial synthesis of phenol (the Dow process ) involves treatment of chlorobenzene with sodium hydroxide and a small amount of water in a pressurized reactor at 350 °C ... 

Notice the symmetry in this mechanism. Benzyne is formed from an ortho carbanion and it gives an ortho carbanion when it reacts with nucleophiles. The whole mechanism from bromobenzene to aniline involves an elimination to give benzyne followed by an addition of the nucleophile to the triple bond of benzyne. In many ways, this mechanism is the reverse of the normal addition-elimination mechanism for nucleophilic aromatic substitution and it is sometimes called the elimination-addition mechanism, the elimination step... 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Addition-elimination mechanism (Section 23 6) Two stage mechanism for nucleophilic aromatic substitution In the addition stage the nucleophile adds to the carbon that bears... 

There are two mechanisms for nucleophilic aromatic substitution. Both occur in two important steps. In one mechanism, an addition is followed by an elimination. In the other mechanism, an elimination is followed by an addition. 

Elimination-addition mechanism for nucleophilic aromatic substitution. Benzyne... 

Elimination-addition mechanism Two-stage mechanism for nucleophilic aromatic substitution. In the first stage, an aryl halide undergoes elimination to form an aryne intermediate. In the second stage, nucleophilic addition to the aryne yields the product of the reaction. 

The addition of a nucleophile to an aromatic ring, followed by elimination of a substituent, results in nucleophilic substitution. The major energetic requirement for this mechanism is formation of the addition intermediate. The addition step is greatly facilitated by strongly electron-attracting substituents, and nitroaromatics are the best reactants for nucleophilic aromatic substitution. Other EWGs such as cyano, acetyl, and trifluoromethyl also enhance reactivity. 

This displaces the third fluorine and all that is left is to hydrolyse the ester to the free acid with aqueous base (Chapter 12). Every single reaction in this quite complicated sequence is one that you have met earlier in the book, and it forms a fitting climax to this section on the addition-elimination mechanism for aromatic nucleophilic substitution. We now need to mention two other less important possibilities. 

Whereas electrophilic attack of benzene is both well known and important, the corresponding reaction with nucleophiles is very difficult and is not typical of aromatic compounds. However, if the aromatic ring is TT-electron deficient because an electron-withdrawing group (EWG) is present, then nucleophilic attack can occur. The mechanism for the addition-elimination sequence for nucleophilic substitution is shown in Scheme 2.17. 

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