12.19:
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Nitrogen nucleophiles like amines undergo addition reactions with carbonyl compounds.
The addition of a primary amine to an aldehyde or a ketone forms a carbinolamine, which loses water to give an imine, also called a Schiff base.
If, instead, a secondary amine is used, the resulting product will be an enamine.
Imines have a C=N double bond, while enamines possess a C–N single bond and an amino group attached to a C=C double bond.
There are two parts common to the formation of imines and enamines: Generation of carbinolamine and elimination of water. Both reactions form a new C=Nu bond.
The two reactions occur under mild acidic conditions. However, unlike imine formation, enamine formation requires a carbonyl substrate with at least one α hydrogen that can be abstracted in the final elimination step.
Imines are biologically important functional groups. Rhodopsin, a visual pigment in the rods of the retina, is an example of a highly conjugated imine.
12.19:
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
Both imine formation and enamine formation are reversible and acid-catalyzed. Maintenance of proper pH of the reaction medium is necessary to control the formation rate. Both reaction mechanisms follow similar steps and can be divided into carbinolamine formation and water elimination. The only difference lies in the final step—imine formation involves proton abstraction from N–H of the iminium ion, whereas enamine formation involves proton abstraction from the α C–H of the iminium ion.
Since the reactions are reversible, both imines and enamines can be converted to carbonyl compounds by hydrolysis. The reaction of carbonyl compounds with hydroxylamines, hydrazines, and semicarbazides results in imine derivatives such as oximes, hydrazones, and semicarbazones, respectively.