Amide Hydrolysis: Introduction and Types Of Amide Hydrolysis

Amides resist hydrolysis. Even with prolonged heating, the amide does not decompose by reacting with water molecules. However, hydrolysis of amides is not impossible. It interacts with water molecules in either acidic or basic media.

In acidic environments, amides react with water molecules to form carboxylic acids and ammonia or amine salts.

In basic media, amides react with water molecules to form carboxylic acids and ammonia or amine salts. In the human body, amide hydrolysis is catalyzed by enzymes.

Amides

Amides are functional groups with a carbonyl group attached to the nitrogen atom by a single bond. Amides are also known as derivatives of carboxylic acids in which the OH group of COOH is replaced by NH2, NHR, NR2 of amines.

Hydrolysis

Hydrolysis is a chemical reaction resulting from the interaction of a chemical substance with water, resulting in the decomposition of both substances and water. Hydrolysis can react with salts, carbohydrates, proteins, fats and many more. It is the chemical breakdown of substances that takes place with the help of water. It is dependent on the chemistry, and the oxidation–reduction processes of the compound.

Types Of Amide Hydrolysis

Amides interact with water molecules in two possible ways-

• Acid Catalysed Amide Hydrolysis

• Base Catalysed Amide Hydrolysis

Acid Catalysed Amide Hydrolysis

Mechanism:

Step 1: Protonation of the amide carbonyl

It activates the amide since only weak nucleophiles and weak electrophiles are available.

Step 2: Nucleophilic Addition

The lone oxygen pair attacks the carbonyl group. Electrons are transferred to the oxonium ion, forming a tetrahedral intermediate.

Step 3: Proton Transfer

Oxygen donates a proton to neutralize its charge.

Step 4: Proton transfer

The proton attacks the -NHR' group, allowing it to readily leave.

Step 5: Elimination of R'-NH2

The oxygen lone pair attacks the carbon atom and displaces the R'-NH2 group.

Step 6: Deprotonate the Oxonium Ion

Oxygen donates a proton to neutralize its charge.

Base-Catalyzed Amide Hydrolysis

In basic media, amides react with water molecules to form carboxylic acids with ammonia or amine salts.

Mechanism:

• In base-catalyzed amide hydrolysis, the amide is heated with the boiling aqueous solution of NaOH or KOH.

• A nucleophilic hydroxide ion is added to the carbonyl carbon which forms an intermediate that is tetrahedral in shape.

• The NR2 group is attacked by protons.

• The oxonium ion then attacks the carbon atom and cleaves HNR2.