Imagine a cyclic β-fluoro-enone reacting with a secondary amine in a conjugate substitution reaction. The normal addition to form the enolate followed by return of the negative charge to expel the fluoride ion gives the product.

Now imagine just the same reaction with two extra double bonds in the ring. These play no part in our mechanism; they just make what was an aliphatic ring into an aromatic one. Conjugate substitution has become nucleophilic aromatic substitution.

The mechanism involves addition of the nucleophile followed by elimination of the leaving group—the addition–elimination mechanism. It is not necessary to have a carbonyl group—any electron-withdrawing group will do—the only requirement is that the electrons must be able to get out of the ring into this anion-stabilizing group. Here is an example with a para-nitro group.

Everything is different about this example—the nucleophile (HO−), the leaving group (Cl−), the anion-stabilizing group (NO2), and its position (para)—but the reaction still works. The nucleophile is a good one, the negative charge can be pushed through on to the oxygen atom(s) of the nitro group, and chloride is a better leaving group than OH.

● A typical nucleophilic aromatic substitution has:

 • a carbonyl, nitro, or cyanide group ortho and/or para to the leaving group.

 • a halide for a leaving group

• an oxygen, nitrogen, or cyanide nucleophile

Since the nitro group is usually introduced by electrophilic aromatic substitution (Chapter 21) and halides direct ortho/para in nitration reactions, a common sequence is nitration followed by nucleophilic substitution.

This sequence is useful because the nitro group could not be added directly to give the fi nal product as nitration would go in the wrong position. The nitrile is meta-directing, while the alkyl group (R) is ortho, para-directing. Two activating electron-withdrawing groups are better than one and dinitration of chloro benzene makes a very electrophilic aryl halide. Reaction with hydrazine gives a useful reagent.

مواضيع ذات صلة

How to reduce carboxylic acids to alcohols

How to reduce amides to amines

The benzyne mechanism

Other nucleophiles

The SN1 mechanism for nucleophilic aromatic substitution: diazonium compounds

The activating anion-stabilizing substituent

The leaving group and the mechanism

The intermediate in the addition–elimination mechanism

Nucleophilic aromatic substitution

Nucleophilic epoxidation

Conjugate substitution reactions

Unsaturated nitriles and nitro compounds