Fischer Esterification Reaction

Introduction

• Purpose: Formation of esters from carboxylic acids, alcohol, and a source of protons.
• Products: Ester and water.
• Equilibrium Considerations: Reaction is at equilibrium. To increase ester yield:
  • Decrease water concentration.
  • Increase alcohol concentration.

Reaction Mechanism

1. Protonation of Carboxylic Acid

   • Protonate the oxygen on carboxylic acid.
   • Increases electrophilicity of the carbon.
   • Carbon becomes more susceptible to nucleophilic attack.

2. Nucleophilic Attack

   • Alcohol acts as a nucleophile.
   • Lone pair on alcohol's oxygen attacks the carbonyl carbon.
   • Forms a bond between carbon and oxygen.

3. Deprotonation

   • Alcohol (acting as a base) deprotonates the oxygen.
   • Removes +1 formal charge on oxygen.

4. Protonation of Hydroxyl Group

   • Hydroxyl group (OH) is protonated to form water, an excellent leaving group.
   • Formation of water leads to elimination from the reaction.

5. Formation of Ester

   • Reform the double bond in carbonyl, releasing water.
   • Final deprotonation step yields the ester product.

Examples of Fischer Esterification

Example 1: Salicylic Acid with Methanol

• Reagents: Salicylic acid, methanol, sulfuric acid (proton source).
• Product: Ester known as wintergreen.
• Significance: Common undergraduate lab experiment due to pleasant aroma.

Example 2: Intramolecular Fischer Esterification

• Characteristics:
  • Carboxylic acid and alcohol present in the same molecule.
  • Free rotation allows bond formation between these groups.
• Process:
  • Alternate conformation allows oxygen to attack carbonyl carbon.
• Product: Lactone (an ester in a ring structure).
  • Specific example: Six-membered ring lactone formed from five-carbon chain.

Summary

• Fischer esterification is a versatile method to synthesize esters.
• Understanding the mechanism helps in manipulating conditions to favor ester formation.
• Intramolecular reactions can result in cyclic esters (lactones).