We have seen that all the steps in the Fischer esterification are reversible and the equilibrium is shifted toward the ester product by using an excess of alcohol.

This nature of the reaction allows to hydrolyze esters back into a carboxylic acid and alcohol when the water is now used in a large excess:

 

 

The reaction works even better by base catalysis (saponification) because it makes the process irreversible. We will see why this happens when discussing the mechanism of each hydrolysis.

 

Acid-Catalyzed Hydrolysis of Esters

Let’s start with the mechanism of acid-catalyzed hydrolysis of esters. Essentially, we are drawing the reverse order of Fischer esterification so, in the first step the ester is protonated promoting the nucleophilic attack of water:

 

 

Notice that just like the Fischer esterification, the process is an equilibrium which makes the reaction a little challenging as it may require higher temperatures and removal of the alcohol as it is formed to push the equilibrium forward.

 

Base-Catalyzed Hydrolysis of Esters

And this is when the base-catalyzed ester hydrolysis turns to be more beneficial. The carboxylic acid formed during the reaction is deprotonated by the alkoxide or the hydroxide ions making the overall reaction irreversible.

Lets’ see how that happens by drawing the complete mechanism of the reaction:

 

 

After the addition of the ^–OH and elimination of the ^–OR, a carboxylic acid is formed. And it quickly reacts with the ^–OH or ^–OR strong bases transforming into a carboxylate ion which is less electrophilic than carboxylic acids and cannot be attacked by the R’O^– alkoxide anymore.

The base-catalyzed ester hydrolysis is also known as saponification because it is used in the production of soaps from fats. Remember, soap is a salt of a fatty acid and can be formed when a fat (an ester derived from a glycerol and three molecules of fatty acid) is hydrolyzed by base catalysis:

 

 

More About the Ester Hydrolysis Mechanism

One interesting question here;

How do we know this is the correct mechanism of base-catalyzed ester hydrolysis?

Let’s consider a specific example of an ester with methyl or primary alkyl derivative:

Can this S_N2 reaction be a suitable alternative to the addition-elimination mechanism we discussed above?

 

 

We have a primary carbon and the acetate is not the worst leaving group – certainly better than the ethoxide. So, does the ethoxide attack the carbonyl carbon or the CH₂ of the ethyl group?

This can be tested by isotope labeling. We take an ester containing ¹⁸O isotope in the alkoxy part and react it with a hydroxide. Now, if the reaction was S_N2, then the ¹⁸O oxygen should still appear in the carboxylate ion:

 

 

However, experimental studies have indicated that the reaction goes by addition-elimination mechanism as the oxygen in the carboxylate comes from the hydroxide ion:

 

 

Hydrolysis of An Ester with a Tertiary Alkyl Group

The isotope labeling and other studies confirming the addition-elimination path wouldn’t be complete if we didn’t find one exception, right?

And that is the acid-catalyzed hydrolysis of esters containing a tertiary alkyl group:

 

 

The products are a carboxylic acid and alcohol just as expected. However, the mechanism is a little different. After the protonation of the carbonyl, instead of the nucleophilic addition to the carbonyl, we have a loss of a leaving group by an S_N1 mechanism:

 

 

This C-O bond cleavage occurs because it produces a relatively stable tertiary alkyl group just like we have seen in the S_N1 mechanism.

To summarize, yes, the nucleophilic addition-elimination mechanism predominates in ester hydrolysis, however, you should not exclude the possibility of S_N2 and S_N1 reactions depending on the structure of the ester.

 

Need some good practice on the reactions of carboxylic acids and their derivatives?

Check this 45-question, Multiple-Choice Quiz with a 50-min Video Solution covering the reactions of acids, esters, lactones, amides, acid chlorides and etc. 

 

Check Also

• Preparation of Carboxylic Acids
• Naming Carboxylic Acids
• Naming Nitriles
• Naming Esters
• Naming Carboxylic Acid Derivatives – Practice Problems
• Fischer Esterification
• What is Transesterification?
• Esters Reaction with Amines – The Aminolysis Mechanism
• Ester Reactions Summary and Practice Problems
• Preparation of Acyl (Acid) Chlorides (ROCl)
• Reactions of Acid Chlorides (ROCl) with Nucleophiles
• R₂CuLi Organocuprates – Gilman Reagent
• Reaction of Acyl Chlorides with Grignard and Gilman (Organocuprate) Reagents
• Reduction of Acyl Chlorides by LiAlH₄, NaBH4, and LiAl(OtBu)₃H
• Preparation and Reaction Mechanism of Carboxylic Anhydrides
• Amides – Structure and Reactivity
• Naming Amides
• Amides Hydrolysis: Acid and Base-Catalyzed Mechanism
• Amide Dehydration Mechanism by SOCl₂, POCl₃, and P₂O₅
• Amide Reduction Mechanism by LiAlH4
• Reduction of Amides to Amines and Aldehydes
• Amides Preparation and Reactions Summary
• Amides from Carboxylic Acids-DCC and EDC Coupling
• The Mechanism of Nitrile Hydrolysis To Carboxylic Acid
• Nitrile Reduction Mechanism with LiAlH4 and DIBAL to Amine or Aldehyde
• The Mechanism of Grignard and Organolithium Reactions with Nitriles
• The Reactions of Nitriles
• Converting Nitriles to Amides
• Carboxylic Acids to Ketones
• Esters to Ketones
• Carboxylic Acids and Their Derivatives Practice Problems
• Carboxylic Acids and Their Derivatives Quiz
• Reactions Map of Carboxylic Acid Derivatives