What is Nucleophilic Aromatic Substitution?

Nucleophilic aromatic substitution is a nucleophilic substitution reaction in which a nucleophile displaces a leaving group bonded to the carbon ring of an aromatic compound. In this reaction, a nucleophile attacks an aromatic ring that is deficient in electrons. The presence of an electron-withdrawing group facilitates the reaction. A typical leaving group is a halide, like fluoride or chloride ^[1-6].

Conditions for Nucleophilic Aromatic Substitution

Here are the facts and conditions for nucleophilic aromatic substitution reaction.

• The attacking species must be a strong nucleophile, i.e., it must have electrons that can bond with the carbon atom of the ring.
• The aromatic ring is poor in electrons, i.e., electron-deficient. The presence of an electron-withdrawing group activates the ring and makes it electron deficient.
• The leaving group is usually a nucleophilic species like a halide (X^–) attached to a carbon atom.
• The nucleophile attacks at a site determined by the leaving group’s position, not by steric and electronic factors.

Examples of Nucleophilic Aromatic Substitution

Here is an example of nucleophilic aromatic substitution ^[2-6].

1-chloro-4-nitrobenzene (Cl-(C₆H₄)-NO₂) reacts with sodium methoxide (CH₃ONa) to produce 1-methoxy-4-nitrobenzene (CH₃O-(C₆H₄)-NO₂).

Cl-(C₆H₄)-NO₂ + CH₃ONa → CH₃O-(C₆H₄)-NO₂ + NaCl

Mechanism of Nucleophilic Aromatic Substitution

There are four main mechanisms for the nucleophilic aromatic substitution involving a benzene ring, nucleophile (Nu), and a leaving group (LG) ^[2-7]. However, the addition-elimination mechanism is very common.

This mechanism is similar to electrophilic substitution, except that an anion instead of a cation intermediate is involved. The introduction of an electron withdrawing group, like nitro (NO₂), makes the system vulnerable to nucleophilic attacks on the aromatic ring. Therefore, the nucleophile adds to the aromatic ring to form a delocalized anion, eliminating the halide leaving group.

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