Nucleophilic aromatic substitution activating groups, effects

In nucleophilic as in electrophilic aromatic substitution, then, a substituent group affects reactivity by its ability to attract or release electrons in nucleophilic as in electrophilic aromatic substitution, a substituent group exerts its effect chiefly at the position ortho and para to it. The kind of effect that each group exerts, however, is exactly opposite to the kind of effect it exerts in electrophilic aromatic substitution. In nucleophilic aromatic substitution electron withdrawal causes activation, and electron release causes deactivation. 

There are similarities between nucleophilic aromatic substitution (SnAt) and its more usual counterpart, electrophilic aromatic substitution. Each involves the formation of a resonance-stabilized intermediate, and each involves a temporary loss of aromaticity that is regained in the final step of the reaction. But the similarities are only so deep. The electrophilic reaction involves cationic intermediates the nucleophilic involves anionic intermediates. Use the differing effects of a nitro group, strongly deactivating in the electrophilic substitution and strongly activating in the nucleophilic substitution, to keep the two mechanisms distinct in your mind. 

For the nucleophilic aromatic substitution reaction (SnAt) it has been discussed whether the addition of the nucleophile, the elimination of the leaving group is the rate limiting step or if this depends on the solvent. Taking the SnAt reaction between azide ion and 4-fluoronitrobenzene as an example, QM/MM calculations indicate that solvation effects cause the highest barrier for the elimination step. As a function of the solvent the experimental free energies of activation for these reactions are (values are given in kcal/mol) H2O 28.1/MeOH 27.5/MeCN ... 

Oxazolines (4) are easily prepared from benzoic acids and behave as activating groups in nucleophilic aromatic substitution. Thus, o-methoxy- or o-fluoro-substituents are replaced by the alkyl group of RLi. " The same oxazoline group in the 4-position of pyridine promotes 3-lithiation, whereas in the 3-position it induces nucleophilic alkylation to give 1,4-dihydropyridine derivatives. Benzyl alcohol is lithiated in the 2-position of the benzene nucleus. Solvent effects are suggested to be responsible for the quantitative syn selectivity in the alkylation of lithiated ketimines (5). ... 

Nucleophilic aromatic substitution reactions have been examined in terms of a model based on the combination of a cation with an anion. The reactivities of 2,4-dinitro-halogenobenzenes with nucleophiles have been shown to be related to the basicity and polarisability of the nucleophile and the polarisability of the substrate only atoms and bonds at or near the reaction centre are involved in producing the polarisability effects. Hammett cr values have been measured for unsaturated groups —CH=NX in the 4-position for nucleophilic displacement of chlorine in 2-nitrochlorobenzene derivatives and compared with those for established activating groups. ... 

The primary mechanism for formation of aryl ether linkages involves nucleophilic aromatic substitution of an activated leaving group by phenolate. Polar aprotic solvents, e.g., dimethylsulfoxide (DMSO), N-methylpyrrolidone (NMP) and dimethylacetamide (DMAC) are required to effect the reaction. The use of dimethylproylene urea has been reported as an alternative solvent... 

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