Imine synthesis

Imines are molecules  that contain C=N group.


Imines belong to that class of compounds deriving from the addition reaction to the carbonyl (C=O). Primary imine is obtained for addition of ammonia (NH3) to an aldehyde or ketone, while secondary imine are obtained by adding primary amines (R-NH2) to aldehydes or ketoons. We can further distinguish  in aldoimines or ketoimines, whether the nitrogen nucleophile adds on an aldehyde or a keton.



The reaction mechanism is extremely comprehensible. On one hand we have a strong nucleophile, amine or ammonia and on the other hand the carbonyl group. In the first step of imine reaction synthesis isn't necessary an acid catalysis, the reaction goes quickly anyway. Here is the first step mechanism:


1)  Nitrogen attacks carbonyl δ+ . π breacks and a new carbon-nitrogen σ bond is formed.

2) Tetrahedral intermediate is unstable. Without a proton exchange (H+) the reaction goes back, with the amine leaving. Instead if the protons exchange proceeds we obtain an hemiaminal, an intermediate similar to the hemiacetal structurally talking.

However to synthesize an imine an acid catalysis is required:


Actually we saw that a strongly acid environment disadvantage the first step of the reaction, because tha amine could be protonated (in this case the amine would behave like a base rather than a nucleophile),while the second step requires an acid catalysis, becauese hydroxyl has to be protonated in order to become a good leaving group.

The problem is solved thanks a compromise, the reaction is done in acid environment but not so much, between pH 4 e 6.

Let's have a look again to the overall reaction:


Don't forget that imines, just like acetals, forms with the simultaneous loss of water.


Actually, imines are (just like acetals) quite unstable and can be isolated (practically) only if a coniugated π system comes out. Here it is an example of a very stable imine that could be eventually synthesized.