Draw the mechanism of the synthesis of benzocaine from 4-aminobenzoic acid and ethanol. Does the mechanism occur by bimolecular nucleophilic substitution or unimolecular nucleophilic substitution and explain why.
The correct answer and explanation is:
Mechanism of the Synthesis of Benzocaine from 4-Aminobenzoic Acid and Ethanol
Overall Reaction:
4-aminobenzoic acid + ethanol → benzocaine (ethyl 4-aminobenzoate) + water
This is an esterification reaction known as Fischer esterification, catalyzed by acid (usually H₂SO₄ or HCl), where a carboxylic acid reacts with an alcohol to form an ester.
Step-by-Step Mechanism:
1. Protonation of the carboxylic acid:
The carbonyl oxygen of the 4-aminobenzoic acid is protonated by an acid catalyst, making the carbon more electrophilic.
2. Nucleophilic attack by ethanol:
Ethanol acts as a nucleophile and attacks the carbonyl carbon, forming a tetrahedral intermediate.
3. Proton transfer:
A proton shifts within the tetrahedral intermediate to prepare for water elimination.
4. Elimination of water:
A water molecule is eliminated, forming a protonated ester.
5. Deprotonation:
The protonated ester loses a proton to form the final product: ethyl 4-aminobenzoate (benzocaine).
Does it occur by SN1 or SN2?
Answer: Neither SN1 nor SN2.
This reaction does not proceed by either bimolecular nucleophilic substitution (SN2) or unimolecular nucleophilic substitution (SN1).
Explanation:
- SN1 and SN2 mechanisms apply to alkyl halides or similar electrophiles, not carboxylic acids.
- In this case, the reaction is a Fischer esterification, which proceeds through an acid-catalyzed addition-elimination mechanism, not substitution.
- The key intermediate is a tetrahedral intermediate, not a carbocation or backside attack.
- SN1 involves a carbocation intermediate; SN2 involves a concerted backside attack—neither is observed here.
- The reaction requires acid catalysis to activate the carboxyl group and make the carbonyl carbon more electrophilic.
Conclusion:
The synthesis of benzocaine from 4-aminobenzoic acid and ethanol occurs via an acid-catalyzed esterification mechanism, not by SN1 or SN2. The mechanism involves protonation, nucleophilic attack, elimination of water, and deprotonation—typical of a Fischer esterification.