Question

Write the mechanism for the acid-catalyzed reaction of an amide with an alcohol to form an ester.

Short answer

Amides react with alcohol to form ester when the reaction mixture is heated in the presence of an acid shown as follows:

Three times tetrahedral intermediate is formed in the reaction mechanism of acid-catalyzed amide alcoholysis, which are :

• Tetrahedral intermediate I formed when nucleophiles attacked the carbonyl carbon.
• Tetrahedral intermediate II is formed when the conjugate base deprotonates the positive atom of the nucleophile.
• Tetrahedral intermediate III is formed when leaving group gets protonated.

Step-by-step solution

Acid-catalyzed amide alcoholysis

Amides react with alcohol to form ester when the reaction mixture is heated in the presence of an acid shown as follows:

Three times tetrahedral intermediate is formed in the reaction mechanism of acid-catalyzed amide alcoholysis, which are :

• Tetrahedral intermediate I formed when nucleophiles attacked the carbonyl carbon.
• Tetrahedral intermediate II is formed when the conjugate base deprotonates the positive atom of the nucleophile.
• Tetrahedral intermediate III is formed when leaving group gets protonated.

Mechanism of acid-catalyzed reaction of the amide with alcohol

The mechanism of the acid-catalyzed reaction of the amide with alcohol to form the ester follows the following step:

• The acid protonates the carbonyl oxygen, which increases the susceptibility of the carbonyl carbon to nucleophilic addition.
• Adding the nucleophile (ROH ) to the carbonyl carbon leads to tetrahedral intermediate I, which is in equilibrium with its non protonated form, tetrahedral intermediate II.
• Re-protonation can occur either on oxygen to re-form tetrahedral intermediate I or on nitrogen to form tetrahedral intermediate III. Protonation on nitrogen is favoured because the group is a stronger base than the ROH group.
• Of the two possible leaving groups in tetrahedral intermediate III (RO and ), it is the weaker base (good leaving group), so it is the one eliminated.
• Ammonia() is protonated after it is eliminated from the tetrahedral intermediate; it prevents the reverse reaction because the ammonium ion is not a nucleophile.