Enamine Reactions

1) Addition of Secondary Amines

Aldehydes and ketones react with secondary amines to form enamines.

Like imine formation, the reaction requires a trace amount of an acid catalyst.

The mechanism for enamine formation is exactly the same as that for imine formation until the last step of the reaction.

When a primary amine reacts with an aldehyde or a ketone, the protonated imine loses a proton from nitrogen in the last step of the reaction, forming a neutral imine.

However, when the amine is secondary, the positively charged nitrogen is not bonded to a hydrogen.

A stable neutral molecule is obtained by removing a proton from the -carbon of the compound derived from the carbonyl compound. An enamine is the result.

In aqueous acidic solutions, an enamine is hydrolyzed back to the carbonyl compound and secondary amine, a reaction that is similar to the acid-catalyzed hydrolysis of an imine back to the carbonyl compound and a primary amine.

2) Reactions of Enamines

Enamines react with electrophiles in the same way that enolates do.

Electrophiles can be added to the α-carbon of an aldehyde or a ketone by first converting the carbonyl compound to an enamine (by treating the carbonyl compound with a secondary amine), adding the electrophile, and then hydrolyzing the imine back to the ketone.

Because the alkylation step is an SN2 reaction, only primary alkyl halides or methyl halides should be used.

One advantage to using an enamine intermediate to alkylate an aldehyde or a ketone is that only the monoalkylated product is formed.

3) To Aviod the following byproducts

In contrast, when a carbonyl compound is alkylated directly, dialkylated and O-alkylated products can also be formed.

Using an enamine intermediate to alkylate an aldehyde or a ketone is that only the monoalkylated product is formed.

4) Acylation of Aldehydes and Ketones:

In addition to being able to be alkylated, aldehydes and ketones can also be acylated via an enamine intermediate.

5) Reactions less substituted site only:

This selectivity derives from the fact that the enamine from an unsymmetrical ketone consists mainly of the more-reactive isomer in which the double bond is directed toward the less substituted carbon atom.

In the "more-substituted" enamine, there is decreased interaction between the nitrogen lone pair and the π-system of the double bond because of steric interference between the α-substituent.

6) Conjugate Addition Reactions of Enamines

Formation of enamines and their alkylation reactions.

An alternative type of alkylation occurs on addition of these nucleophiles to electrophilic alkenes, such as α,β-unsaturated ketones, esters.

Examples:

NOTE:

a) Requires secondary amines only.

b) Require catalytic acidic condition.

c) Always prefers less substituted site only.