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Reactions of Aromatic Compounds - Nucleophilic Aromatic Substitution Ar-SN

Nucleophilic Aromatic Substitution (Ar-SN)

Electrophilic aromatic substitution is considerably promoted by electron-donating first substituents. That is, the electron density of the π electron system is increased. Thus, the π electron cloud's nucleophilic attack on the electrophile is easily made possible. On the other hand, the question is, whether or not strong electron-withdrawing first substituents may enable a nucleophilic attack on a carbon of the aromatic ring.

In fact, the halogen atom (Cl, Br, or I) of substituted halobenzenes that carry two nitro groups in ortho and para position, for instance, is actually substituted by a nucleophilic attack of a good nucleophile, such as OCH3.

Nucleophilic substitution of chloride for methoxide in chloro-2,4-dinitrobenzene.

Electrostatic potential surface of chlorobenzene.


Electrostatic potential surface of chloro-2,4-dinitrobenzene.

Comparison of the electrostatic potential surfaces illustrates the considerably stronger chlorine-carrying carbon's positive polarization by the electron-withdrawing nitro groups, which enables a nucleophilic attack on this carbon (red means a more negative potential, blue means a more positive potential).

The reaction proceeds more easily according to the number of electron-withdrawing substituents the aromatic compound possesses. However, substituents in ortho and para position, above all, promote a nucleophilic attack, while substituents in meta position almost never do. These observations may be explained by a mechanism that resembles the electrophilic aromatic substitution's mechanism and that represents, so to speak, its "nucleophilic counterpart".

Mechanism of the nucleophilic aromatic substitution.

Analogous to electrophilic aromatic substitution, the mechanism of nucleophilic aromatic substitution is an addition-elimination mechanism. However, in the first, rate-determining step, the aromatic π system is broken by the attack of a nucleophile (Nu) on the aromatic ring and not by a nucleophilic attack of the aromatic compound's π electron cloud on an electrophile. Consequently, it is not a carbocation but an intermediate carbanion that is formed. The negative charge of the carbanion is delocalized. It is distributed among the five remaining, formerly aromatic, sp2-hybridized ring carbons. Finally, the aromatic π system is recovered when the leaving group "X" is split off. The conceivable elimination of the nucleophile, which would lead back to the starting products, hardly ever occurs, as a good nucleophile is usually also a poor leaving group.

An additional delocalization and, thus, stabilization of the intermediate carbanion's negative charge through conjugation with -M and -I substituents is possible when these substituents are in ortho or para position regarding the sp3 ring carbon. Stabilization by a -I substituent is at its highest when the substituent is bound to the center that possesses the largest negative charge density, that is, if it is in para position. However, stabilization by a -I substituent in ortho position is merely a bit smaller.

Resonance structures of intermediate carbanions with a -M substituent in nucleophilic aromatic substitution.

If the nucleophile (Nu) as well as the desired nucleofuge (X) are poor leaving groups and the aromatic compound possesses three nitro groups in ortho and para positions, the intermediate carbanion of a nucleophilic aromatic substitution is stable enough to be isolated. These stable carbanions are known as Meisenheimer complexes, while nonisolable intermediate carbanions of nucleophilic aromatic substitutions are termed Meisenheimer complex-analogous intermediates.

Meisenheimer complex and Meisenheimer complex-analogous intermediate.

The electrostatic potential surface of the Meisenheimer complex illustrates the stabilization by the strong delocalization (no position with considerable charge localization, that is, no intensively red or blue coloured areas, which would indicate strongly negative or positive electrostatic potentials).

The reactivity of nucleophilic anions may be noticeably increased when the reaction is carried out in a polar, aprotic solvent. In such solvents, the anion is soluble, though it cannot be stabilized by hydrogen bridge bonds. Under these conditions, nucleophilic aromatic substitution may also occur with halobenzenes that are not further activated through additional substituents.

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