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 Nitriles

Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution

nucleophilic addition of nitriles
Reaction type:  Nucleophilic Addition

Overview

        versus nucleophilic addition of aldehyes and ketones
Addition of strong nucleophiles to nitriles

Hydrolysis of Nitriles

hydrolysis of nitriles
Reaction type:  Nucleophilic Addition then Nucleophilic Acyl Substitution

Summary

Related Reactions
 
MECHANISM OF THE ACID catalyzed HYDROLYSIS OF NITRILES
Step 1:
An acid/base reaction. Since we only have a weak nucleophile so activate the nitrile, protonation makes it more electrophilic.
hydrolysis of a nitrile with acid catalysis
Step 2:
The water O functions as the nucleophile attacking the electrophilic C in the CºN, with the electrons moving towards the positive center. 
Step 3:
An acid/base reaction. Deprotonate the oxygen that came from the water molecule. The remaining task is a tautomerization at N and O centers.
Step 4:
An acid/base reaction. Protonate the N gives us the -NH2 we need.... 
Step 5:
Use the electrons of an adjacent O to neutralise the positive at the N and form the p bond in the C=O. 
Step 6:
An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the amide intermediate....halfway to the acid..... 
What about the rest



 

Reduction of Nitriles
(for more detail see Chapter 22)

reduction of nitrile to primary amine
Reactions usually in Et2O or THF followed by H3O+ work-up
Reaction type: Nucleophilic Addition

Summary

Reactions of RLi or RMgX with Nitriles

reaction of RLi or RMgX with nitriles
Reaction usually in Et2O or  THF
Reaction type:  Nucleophilic Acyl Substitution then Nucleophilic Addition

Summary:

addition of a Grignard to a nitrile giving the ketone
REACTION OF RMgX WITH AN NITRILE
Step 1:
The nucleophilic C in the organometallic reagent adds to the electrophilic C in the polar nitrile group. Electrons from the CºN move to the electronegative N creating an intermediate imine salt complex.
addition of Grignard reagent to an nitrile
Step 2:
An acid/base reaction. On addition of aqueous acid, the intermediate salt protonates giving the imine.
Step 3:
An acid/base reaction. Imines undergo nucleophilic addition, but require activation by protonation (i.e. acid catalysis)
Step 4:
Now the nucleophilic O of a water molecule attacks the electrophilic C with the p bond breaking to neutralize the change on the N.
Step 5:
An acid/base reaction. Deprotonate the O from the water molecule to neutralize the positive charge.
Step 6:
An acid/base reaction. Before the N system leaves, it needs to be made into a better leaving group by protonation.
Step 7:
Use the electrons on the O in order to push out the N leaving group, a neutral molecule of ammonia.
Step 8:
An acid/base reaction. Deprotonation reveals the carbonyl group of the ketone product.


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