Return to Contents Chapter 20: Carboxylic Acid Derivatives. NucleophilicAcyl Substitution Ch 20 contents Hydrolysis of Esters

hydrolysis of esters Reaction type: Nucleophilic Acyl Substitution

Summary

Carboxylic esters hydrolyse to the parent carboxylic acid and an alcohol. Reagents : aqueous acid (e.g. H2SO4) / heat,or aqueous NaOH / heat (known as "saponification"). These mechanisms are among some of the most studied in organic chemistry. Both are based on the formation of a tetrahedral intermediate which then dissociates. In both cases it is the C-O bond between the acyl group and the oxygen that is cleaved. Related Reactions Fischer esterification Hydrolysis of Amides Reaction under BASIC conditions: The mechanism shown below leads to acyl-oxygen cleavage (see step2). The mechanism is supported by experiments using 18O labeled compounds and esters of chiral alcohols. This reaction is known as "saponification" because it is the basis of making soap from glycerol triesters in fats. The mechanism is an example of the reactive system type. MECHANISM OF THE BASE HYDROLYSIS OF ESTERS

Step 1: The hydroxide nucleophiles attacks at the electrophilic C ofthe ester C=O, breaking the π bond and creating the tetrahedral intermediate. hydrolysis of an ester using hydroxide Step 2: The intermediate collapses, reforming the C=O results in the loss of the leaving group the alkoxide, RO-, leading to the carboxylic acid. Step 3: An acid / base reaction. A very rapid equilibrium where the alkoxide,RO- functions as a base deprotonating the carboxylic acid, RCO2H, (an acidic work up would allow the carboxylic acid to be obtained from the reaction).

Reaction under ACIDIC conditions:

Note that the acid catalysed mechanism is the reverse of the Fischer esterification. The mechanism shown below also leads to acyl-oxygen cleavage (see step 5). The mechanism is an example of the less reactive system type. MECHANISM OF THE ACID CATALYSED HYDROLYSIS OF ESTERS Step 1: An acid/base reaction. Since we only have a weak nucleophile and a poor electrophile we need to activate the ester. Protonation of the ester carbonyl makes it more electrophilic. hydrolysis of an ester with acid catalysis Step 2: The water 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 oxygen that came from the water molecule to neutralise the charge. Step 4: An acid/base reaction. Need to make the -OCH3 leave, but need to convert it into a good leaving group first by protonation. Step 5: Use the electrons of an adjacent oxygen to help "push out" the leaving group, a neutral methanol molecule. Step 6: An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl C=O in the carboxylic acid product and regenerates the acid catalyst.