Important reactions for carboxylic acid derivatives include nucleophilic substitution, transesterification, and hydrolysis of amides.
The direct conversion of a carboxylic acid to an amide is difficult because amines are very basic and tend to convert carboxylic acids to their highly unreactive carboxylate ions. Therefore, DCC (Dicyclohexylcarbodiimide) is used to drive this reaction.
A carboxylic acid first adds to the DCC molecule to form a good leaving group, which can then be displaced by an amine during nucleophilic substitution to form the corresponding amide. The reaction steps are shown below:
Step 1: Deprotonation of the acid.
Step 2: Nucleophilic attack by the carboxylate.
Step 3: Nucleophilic attack by the amine.
Step 4: Proton transfer.
Step 5: Dicyclohexylurea acts as the leaving group to form the amide product.
Transesterification or Fischer esterification is when a carboxylic acid and an alcohol react in acidic conditions to give an ester.
Below is the mechanism of the process:
The hydrolysis of amides generally does not occur in water, but with the presence of an acid or base, it can proceed at a moderate rate.
Hydrolysis of an amide in acid solution actually gives a carboxylic acid and the salt of ammonia or an amine (the ammonia or amine initially formed is neutralized by the acid). Basic hydrolysis gives a salt of the carboxylic acid and ammonia or an amine.
Enzymes also catalyze amide hydrolysis:
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Key Points
• The direct conversion of a carboxylic acid to an amide is difficult, so dicyclohexylcarbodiimide is used to drive this reaction.
• Amides can be made from carboxylic acids through nucleophilic substitution.
• Esters can be made through transesterification by reacting a carboxylic acid with an alcohol in acidic conditions.
• The hydrolysis of amides will produce a carboxylic acid.
Key Terms
Nucleophilic substitution: A fundamental class of reactions in which a leaving group is replaced by an electron-rich compound.
Transesterification: The process of exchanging the organic group R″ of an ester with the organic group R′ of an alcohol.
Hydrolysis of amides: When amides are hydrolysed in the presence of dilute acids such as dilute hydrochloric acid. The acid acts as a catalyst for the reaction between the amide and water.