12.20:
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imine formation is acid-catalyzed and reversible, and its mechanism has two parts.
The first part begins with a nucleophilic attack of the amine to generate a dipolar intermediate.
Mildly acidic ammonium ion, generated from the amine and a strong acid, further catalyzes the reaction by protonating the intermediate, followed by deprotonation to give a carbinolamine.
In the second part, the hydroxyl group is protonated to make a better leaving group to facilitate the further reaction. The loss of water forms an iminium ion, which subsequently deprotonates to produce an imine.
The pH of the solution dictates the overall rate of imine formation.
The first step proceeds slowly under strongly acidic conditions where most amine molecules are protonated and non-nucleophilic, incapable of attacking the carbonyl group.
Under strongly basic conditions, the fourth step is slow due to excess base and no proton donors, thereby inhibiting protonation of the carbinolamine and consequently the formation of iminium ions.
To summarize, imine formation is the slowest at low and high pH values and fastest at around pH 4.5.
12.20:
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the first step—this is when the lone pair on the nitrogen atom of the amine attacks the carbonyl carbon of the substrate. A low pH indicates a high concentration of the protonated form of amine. The protonated amine cannot function as a nucleophile, slowing down this step’s rate.
If the pH is high or the solution is too basic, the fourth step of the reaction mechanism is affected. This is when the hydroxyl group of the carbinolamine is protonated to generate the leaving group, water. Highly basic conditions inhibit the process of water elimination by making the protonated amine, the proton donor in this step, less available for the reaction.
