Depto. Química Orgánica

REACTIVITY OF AMIDES

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15/07/2017
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Amides are the least reactive among all carboxylic acid derivatives because the electrophilicity of the C=O group is heavily reduced by the electron-donor nitrogen. Despite that, there are some interesting reactions...
Acidic or Basic Hydrolysis
The hydrolysis of an amide is usually difficult a process that requires strong acids or bases and high temperatures.
IMPORTANT: If there are other functions present, they wouldn't endure the reaction.
As it is customary, the addition-elimination mechanism applies.
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Hydride Reduction
Amides can only be reduced with strong hydrides like LiAlH4 (LAH).
NaBH4 DOES NOT REACT.
IMPORTANT: Beware other groups' competition!Image
Hofmann Rearrangement
The reaction of amiDes ("with D") with bromine in basic medium induces the C=O loss and the formation of an amiNe ("with N").
IMPORTANT: DO NOT BE CONFUSED...
with the Hofmann Degradation.
Click here to remember it.
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The mechanism is rather complex but maintains the usual logic. It implies the rearrangement of a carbon towards nitrogen.
Click here to recall another mechanism involving carbon rearrangement:

Baeyer-Villiger oxidation of aldehydes and ketones.
Click here to recall another mechanism involving carbon rearrangement:

 Amides from oximes by  Beckmann rearrangement.
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Remember that amines can be hardly prepared by simple nuclophilic substitution. Hofmann rearrangement is an excellent alternative as it is shown in the following retrosynthetic scheme:
 Click here to recall the inconveniences.
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Reaction with Nitrous Acid Sodium nitrite is a common food additive. It can react with the HCl from the stomach leading to the highly reactive nitrosyl cation.
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Nitrosyl cation can react with the amide and amine groups of proteins and enzimes of our body, giving rise to dangerous carcinogenic compounds.
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