What is the base catalyzed amide hydrolysis mechanism?

1 Answer
Apr 18, 2017

To make this very simple, I will try not to go into details and explain the basics.

Explanation:

Amides are molecules that can form from a carboxylic acid and an amine group. In our body, when two amino acids come together to react, they form an amide bond, releasing H2O in the process. This type of bond is also called a peptide bond.

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1.
https://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial2.htmhttps://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial2.htm

To begin, we know that in the first step, a strong base is going to be used like NaOH, where the OH will act as the nucleophile and attack the electrophile, the partial positive carbon of the carbonyl group.

Now, when the bond forms between the oxygen of the OH group and the carbon, the π bond of the carbonyl is broken and the electrons are pushed toward oxygen, leaving it with a negative 1 charge.

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2.https://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial3.htmhttps://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial3.htm

Oxygen will try to remove this negative charge by reforming a double bond with the carbon. But since we know that the carbon atom cannot form more than 4 bonds, the bond between it and the amine's nitrogen has to be broken. The electrons will be pushed onto the nitrogen of the amine and the amine will act as the leaving group (a poor one at that)

*The reason the amine is a poor leaving group is because the amine is a strong base, and strong bases are very unstable. Leaving groups are based off their stability in solution, like the halides, tosylate, H2O

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3.
https://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial4.htmhttps://chemistry.boisestate.edu/richardbanks/organic/amidehydrolysisbasictutorial4.htm

Here, the NH2will act as a base and pluck off the H from the carboxylic acid - type of acid-base reaction. When this happens, a carboxylate anion forms and NH3.