Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution

Reactions of Nitriles

Overview

• Nitriles typically undergo nucleophilic addition to give products that often undergo a further reaction.
• The chemistry of the nitrile functional group, C≡N, is very similar to that of the carbonyl, C=O of aldehydes and ketones. Compare the two schemes:

        versus 

• However, it is convenient to describe nitriles as carboxylic acid derivatives because:
• the oxidation state of the C is the same as that of the carboxylic acid derivatives.
• hydrolysis produces the carboxylic acid
• Like the carbonyl containing compounds, nitriles react with nucleophiles via two scenarios:

• Strong nucleophiles (anionic) add directly to the C≡N to form an intermediate imine salt that protonates (and often reacts further) on work-up with dilute acid.

            Examples of such nucleophilic systems are :  RMgX, RLi, RC≡CM, LiAlH₄
 
• Weaker nucleophiles (neutral) require that the C≡N be activated prior to attack of the Nu.

     This can be done using a acid catalyst which protonates on the Lewis basic N and makes the system more electrophilic.




            Examples of such nucleophilic systems are :  H₂O, ROH
 

The protonation of a nitrile gives a structure that can be redrawn in another resonance form that reveals the electrophilic character of the C since it is a carbocation.

© Dr. Ian Hunt, Department of Chemistry