ORGANIC CHEMISTRY II

Mechanism of Acid-Catalyzed Amide Hydrolysis

Acid-catalyzed amide hydrolysis proceeds via
the customary two stages:

                1)            formation of tetrahedral intermediate
                2)            dissociation of tetrahedral intermediate

First stage:  formation of tetrahedral intermediate

water adds to the carbonyl group of the amide

this stage is analogous to the acid-catalyzed addition of water to a ketone

Second stage:  cleavage of tetrahedral
intermediate

Mechanism of formation of tetrahedral intermediate

Step 1

carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance).

Step 2

Step 3

Cleavage of tetrahedral intermediate

Step 4

Step 5

Step 6

Mechanism of Amide Hydrolysis in Base

Involves two stages:

                1)            formation of tetrahedral intermediate
                2)            dissociation of tetrahedral intermediate

First stage:  formation of tetrahedral intermediate

water adds to the carbonyl group of the amide

this stage is analogous to the base-catalyzed addition of water to a ketone

Second stage:  cleavage of tetrahedral intermediate

Mechanism of formation of tetrahedral intermediate

Step 1

 

Step 2

 

Dissociation of tetrahedral intermediate

Step 3

Step 4

Step 5