91Ó°ÊÓ

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.

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.