Amide Hydrolysis

What is an Amide?

An amide is a functional group in which a carbonyl group is linked with the nitrogen atom by a single bond.

Amide is also known as derivatives of carboxylic acids having an OH group of COOH replaced by an NH₂, NHR, NR₂ of an amine.

What is Hydrolysis?

Hydrolysis is a chemical reaction of the interaction of chemicals with water, leading to the decomposition of both the substance and water.

Table of Content

• Hydrolysis of Amide
• Types of Amide Hydrolysis
• Acid Catalysed Amide Hydrolysis
• Base Catalysed Amide Hydrolysis
• Frequently Asked Questions – FAQs

Hydrolysis of Amide

Amide resists hydrolysis; even after prolonged heating, amide does not interact with water molecules to decompose. However, hydrolysis of amide is not impossible. It interacts with water molecules either in an acidic or a basic medium.

In an acidic medium, amide interacts with the water molecule to give a carboxylic acid and the salt of ammonia or amine salt.

In a basic medium, amide interacts with the water molecule to give a carboxylic acid and the salt of ammonia or amine salt.

• In the human body, amide hydrolysis is catalysed by enzymes.

Types of Amide Hydrolysis

Amide interacts with a water molecule in two possible ways i.e.

• Acid Catalysed Amide Hydrolysis
• Base Catalysed Amide Hydrolysis

Acid Catalysed Amide Hydrolysis

In an acidic medium, amide interacts with the water molecule to give a carboxylic acid and the salt of ammonia or amine salt.

Mechanism:

Step 1: Protonation of amide carbonyl

We will activate the amide since we only have a weak nucleophile and a poor electrophile.

Protonation of the amide carbonyl makes it more electrophilic.

Step 2: Nucleophilic Addition

Lone pairs of oxygen would attack the carbonyl group; the electron would move towards oxonium ion, forming a tetrahedral intermediate.

Step 3: Proton transfer

Oxygen loses a proton to neutralise the charge.

Step 4: Proton transfer

Proton attacks on -NHR’ group so that it can leave effortlessly.

Step 5: Elimination of R’-NH₂

Lone pairs of oxygen attack the carbon atom to push out the R’-NH2 group.

Step 6: Deprotonation of oxonium ion

Oxygen loses a proton to neutralise the charge.

Base Catalysed Amide Hydrolysis

In a basic medium, amide interacts with the water molecule to give a carboxylic acid and the salt of ammonia or amine salt.

Mechanism:

• In base catalysed amide hydrolysis, the amide is heated with boiling aqueous NaOH or KOH.
• The nucleophilic hydroxide ion adds to the carbonyl carbon to form a tetrahedral intermediate.
• Proton attacks the NR2 group.
• Oxonium ion attacks the carbon atom.
• HNR2 is cleaved.