Imine formation using an aldehyde/ketone and primary amine is acid - catalyzed, yet the rate drops below pH 4.5. Why does the rate drop below this pH?

Options

A. The carbinolamine intermediate is stable at low pH
B. The imine product is hydrolyzed at low pH
C. Protonation of the amine decreases its nucleophilicity
D. The amine is hydrolyzed at low pH

Answer

To understand why the rate of imine formation drops below pH 4.5, we need to analyze the reaction mechanism and the role of pH in the reaction involving an aldehyde or ketone and a primary amine.

### Step-by-Step Solution:

1. **Understanding Imine Formation**:
- Imine formation involves the reaction of an aldehyde or ketone with a primary amine (R-NH2) in an acid-catalyzed medium. The general reaction can be represented as:
\[ \text{RCHO (or RCO-R')} + \text{R-NH}_2 \xrightarrow{\text{acid}} \text{R-C(=N-R')} + \text{H}_2\text{O} \]
- Here, RCHO is an aldehyde, and RCO-R' is a ketone. The product is an imine (R-C=N-R').

2. **Role of Acid**:
- The acid (H+) in the reaction increases the electrophilicity of the carbonyl carbon (C=O) by protonating the oxygen atom. This makes the carbon more susceptible to nucleophilic attack by the amine.

3. **Mechanism Overview**:
- The nucleophile (amine) attacks the electrophilic carbon, forming a carbinolamine intermediate (R-C(OH)(NH2)-R').
- This intermediate can then lose a water molecule to form the imine.

4. **Effect of pH on the Reaction**:
- At low pH (below 4.5), the concentration of H+ ions is high. The primary amine (R-NH2) can be protonated to form R-NH3+.
- The protonation of the amine decreases its nucleophilicity because the positively charged ammonium ion (R-NH3+) is less nucleophilic than the neutral amine (R-NH2).

5. **Conclusion**:
- As the pH drops below 4.5, the increased protonation of the amine leads to a decrease in its nucleophilicity, which in turn slows down the rate of imine formation. Therefore, the main reason for the drop in reaction rate at pH below 4.5 is:
\[ \text{Protonation of the amine decreases its nucleophilicity.} \]