Chapter 27: Amino Acids, Peptides and Proteins

Summary

• This reaction is also known as the Fischer esterification.
• Esters are obtained by refluxing the parent carboxylic acid with the appropraite alcohol with an acid catalyst.
• The equilibrium can be driven to completion by using an excess of either the alcohol or the carboxylic acid, or by removing the water as it forms.
• Alcohol reactivity order :  CH₃OH > 1^o > 2^o > 3^o (steric effects)
• Esters can also be made from other carboxylic acid derivatives, especially acyl halides and anhydrides, by reacting them with the appropriate alcohol in the presence of a weak base (see chapter 20)
• If a compound contains both hydroxy- and carboxylic acid groups, then cyclic esters or lactones can form via an intramolecular reaction. Reactions that form 5- or 6-membered rings are particularly favourable.

Study Tip: The carboxylic acid and alcohol combination used to prepare an ester are reflected by the name of the ester,  e.g. ethyl acetate (or ethyl ethanoate), CH3CO2CH2CH3  can be made from CH3CO2H, acetic acid (or ethanoic acid) and HOCH2CH3 (ethanol).  This general "disconnection" is shown below:

MECHANISM FOR REACTION FOR ACID CATALYSED ESTERIFICATION
Step 1: An acid/base reaction. Protonation of the carbonyl makes it more electrophilic.
Step 2: The alcohol O functions as the nucleophile attacking the electrophilic C in the C=O, with the electrons moving towards the oxonium ion, creating the tetrahedral intermediate.
Step 3: An acid/base reaction. Deprotonate the alcoholic oxygen.
Step 4: An acid/base reaction. Need to make an -OH leave, it doesn't matter which one, so convert it into a good leaving group by protonation.
Step 5: Use the electrons of an adjacent oxygen to help "push out" the leaving group, a neutral water molecule.
Step 6: An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the ester product.

© Dr. Ian Hunt, Department of Chemistry