Hydrolysis of nitriles with aqueous acid to give carboxylic acids

by James

Description: Addition of water and acid to a nitrile leads to formation of a carboxylic acid.
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Notes:

  • This reaction is referred to as “acidic hydrolysis”.
  • The reaction is generally used with water as solvent, so an excess of water is present. The acid used is often written as “H3O(+)”

Examples:

Notes: Note that example 4 is a cyanohydrin, so this produces an “alpha hydroxy carboxylic acid”

Mechanism: Protonation of the nitrile nitrogen by acid (Step 1, arrows A and B) makes the nitrile carbon a better electrophile. Attack at the carbon by water (Step 2, arrows C and D) followed by proton transfer (Step 3, arrows E and F) gives a species that is in resonance with a protonated amide (arrows G and H). Addition of water to the protonated amide (Step 4, arrows I and J) followed by proton transfer (Step 5, arrows K and L) result in formation of NH3(+) which is an excellent leaving group. Expulsion of NH3 through 1,2-addition (Step 6, arrows M and N) followed by deprotonation (Step 7, arrows O and P) give the carboxylic acid.

3-mech

Notes:

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{ 3 comments… read them below or add one }

mohammadreza

do you have a convenient metod based on articles for this reaction??

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Stephanie Honig

missing a H on NH4+ -OSO3 in product??

Reply

James

Oops – yes. Sorry, let me fix that. Thanks for spotting

Reply

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