Question

The optimal pH for condensing an amine with a carbonyl group to create an imine is pH = 5-6. a. Show a predicted reaction mechanism using curved arrows to show how this reaction occurs. b. If the pH were higher, which steps would be more difficult? Explain. c. If the pH were lower, which steps would be more difficult? Explain.

Answer 1

Let us see first the very general reaction of formation of imine from amine and carbonyl group:

The mechanism of imine formation involves various kinds of reactions like nucleophilic addition, elimination which accompanied byprotonation-deprotonation reactions.

We can see that very first step is the nucleophilic attack amine on carbonyl carbon atom. Amines themselve are not very good nucleophile (like -vely charged conjugate bases of weak acid are) i.e. they are relatively weak nucleophiles. There nucleophilicity is associated with the ease of availability of lone pair of electron on N for donation to electrophilic carbonyl carbon. But at lower pH i.e. under high concentration of protons, amines get protonated with donation of lone pair of eletrons to proton and amine becomes +vely charged. Hence amines are no longer nucleophilic and also being +vely charged are electrostatically repelled by carbonyl C and nucleophilic attck step i.e. Step I is obscured.

Hence at pH < 5, step-I will be difficult.

Now let us see conversion of III into IV. Here -OH need to be protonated (-H2O⁺) so that lone pair on N could knock out H2O and form N=C bond. But if proton concentration is less i.e. pH is high then this step will be difficult.

Hence at pH > 6 , step III to IV conversion will be difficult.

Hence the optimal pH range for the imine formation is 5-6 pH unit