Book Cover Organic Chemistry 4e Carey
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Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution



Summary | Reactions of Acyl Halides | Reactions of Acid Anhydrides | Reactions of Esters | Reactions of Amides | Reactions of Nitriles |


Reactions of Amides

Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution

Interconversion Reactions of Amides

hydrolysis of amides
Reaction type:  Nucleophilic Acyl Substitution

Summary

Hydrolysis of Amides

hydrolysis of amides
Reaction type:  Nucleophilic Acyl Substitution

Summary

Related Reactions Reaction under ACIDIC conditions:
MECHANISM OF THE ACID catalyzed  HYDROLYSIS OF AMIDES
Step 1:
An acid/base reaction. Since we only have a weak nucleophile and a poor electrophile we need to activate the ester. Protonation of the amide carbonyl makes it more electrophilic.
hydrolysis of an ester with acid catalysis
Step 2:
The water O functions as the nucleophile attacking the electrophilic C in the C=O, with the electrons moving towards the oxonium ion, creating the tetrahedral intermediate.
Step 3:
An acid/base reaction. Deprotonate the oxygen that came from the water molecule.
Step 4:
An acid/base reaction. Need to make the -NH2 leave, but need to convert it into a good leaving group first by protonation.
Step 5:
Use the electrons of an adjacent oxygen to help "push out" the leaving group, a neutral ammonia molecule.
Step 6:
An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the carboxylic acid product and regenerates the acid catalyst.

 

Reduction of Amides
(for more detail see Chapter 22)

reduction of amides using LiAlH4
Reactions usually in Et2O or THF followed by H3O+ work-ups
Reaction type:  Nucleophilic Acyl Substitution then Nucleophilic Addition

Summary

hydride reductions of different types of amides
REACTION OF LiAlH4 WITH AN AMIDE
Step 1:
The nucleophilic H from the hydride reagent adds to the electrophilic C in the polar carbonyl group of the ester. Electrons from the C=O move to the electronegative O creating an intermediate metal alkoxide complex.
reduction of an amide using hydride
Step 2:
The tetrahedral intermediate collapses and displaces the O as part of a metal alkoxide leaving group, this produces a highly reactive iminium ion an intermediate.
Step 3:  
Rapid reduction by the nucleophilic H from the hydride reagent as it adds to the electrophilic C in the iminium system. p electrons from the C=N move to the cationic N neutralizing the charge creating the amine product.


 



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