Carbanions nucleophilic aromatic substitution

Nucleophilic Aromatic Substitution. An activated aromatic haUde is heated at 100—200°C with the alkaU metal salt of the nucleophile (ArOy ROy Ey CN /Cu", carbanion, etc) and the catalyst in an inert solvent (toluene, chiorohen2ene) for a few minutes to a day (21—24). 

There are not many successful examples of arylation of carbanions by nucleophilic aromatic substitution. A major limitation is the fact that aromatic nitro compounds often react with carbanions by electron-transfer processes.111 However, such substitution can be carried out under the conditions of the SRN1 reaction (see Section 11.4). 

Nucleophilic Aromatic Substitution. A natural extension of alkene addition processes is aromatic nucleophilic substimtion. Again, the ease of the process is highly dependent on the stability of the intermediate carbanion and strong EWGs are needed to facilitate these reactions in solution. The classic example is the... 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

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... 

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

For reactions involving an intermediate carbonium ion, we have seen that the overall rate depends only on the rate of formation of the carbonium ion. In nucleophilic aromatic substitution an analogous situation seems to exist the first step, formation of the carbanion, largely determines the overall rale of reaction once formed, the carbanion rapidly reacts to yield the final product. 

Figure 25.3. Potential energy changes during course of reaction nucleophilic aromatic substitution. Formation of carbanion is rate-controlling step strength of C--X bond docs not affect over-all rate.

Nucleophilic aromatic substitution on nitrochlorobenzenes. Oniy the ortho and para intermediate carbanions are resonance-stabilized, so only the ortho and para isomers undergo reaction. 

The range of nucleophiles that can participate in nucleophilic aromatic substitution is similar to the range of those that participate in, 1 reactions and includes alkoxides, " phenoxides, sulfides, fluoride ion, and amines. For reaction with aromatic amines with l-chloro-2,4-dinitrobenzene, the value of p is —4.0, indicting a substantial buildup of positive charge at nitrogen in the TS. Substitution by carbanions is somewhat less common. This may be because there are frequently... 

Note the differences between electrophilic and nucleophilic aromatic substitutions Electrophilic substitutions are favored by electron-donating substituents, which stabilize the carbocation intermediate, while nucleophilic substitutions are favored by electron-withdrawing substituents, which stabilize a carbanion intermediate. The electron-withdrawing group that deactivate rings for electrophilic substitution (nitro, carbonyl, cyano. and so on) activate them for nucleophilic substitution. What s more, these groups are meta directors in electrophilic substitution, but are ortho-para directors in nucleophilic substitution. 

Arylchromium complex 733 reacts with carbon nucleophiles via nucleophilic aromatic substitution. As shown in Table 8.29,6 3 organolithium reagents and enolates add to 733 to generate a carbanionic complex... 

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