ADDITION OF AMINES TO CARBONYLS

15/07/2017

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Amines are good nucleophiles. We've already seen how they might attack a compound with a good leaving group.
Amines may also attack a carbonyl group whose carbon is electron defficient.
The product of the reaction is an imine with a C=N double bond.

How is the reaction mechanism?
To see it in movement might be very instructive but it maybe is very complex to the eye.

The mechanism of the formation of an imine through the attack of an amine to a carbonyl is named addition-elimination.

Let's break it down into its different steps.

Acid catalysis produces the protonation of some ketone molecules. These few protonated ketones have their carbon electrophilicity enhanced.
The nucleophile addition of the amine nitrogen is thus highly facilitated.
The former carbonyl carbon changes from planar sp2 to tetrahedral sp3.

The protonated tetrahedral intermediates give up one proton to the amine molecules that didn't react yet, producing a geminal aminoalcohol (geminal = both functions bonded to the very same carbon) of high stability.

Part of the aminoalcohol molecules suffer protonation on the OH which is feebly basic, leading to an intermediate with an excellent leaving group: water.

The weakened C-O bond, due to the protonation, heterolytically breaks up leading to an intermediate immonium ion.
The former carbonyl carbon, that changed from sp2 to sp3, recovers the sp2 hybridization.

The excess of amine deprotonates the immonium salt, yielding the final imine.

Unfortunately, the overall reaction is not thermodynamically favored in many cases. Therefore, it is necessary to shift all the equilibria by removing the produced water with either a drying agent (molecular sieves, etc.) or a Dean-Stark apparatus.