Hydrolysis of imines to give ketones (or aldehydes)

by James

Description: Treatment of imines with water leads to their hydrolysis back to aldehydes (or ketones) and an amine.

Notes: The reaction is assisted through the use of an acid catalyst.

Examples:

Notes: Note that the third example is intramolecular.

Mechanism: Protonation of the imine nitrogen (Step 1, arrows A and B) results in the formation of the iminium ion, which undergoes 1,2-addition by water (Step 2, arrows C and D). Transfer of a proton (Step 3, arrows E and F) followed by 1,2 elimination of ammonia (Step 4, arrows G and H) lead to an oxonium ion, which is then deprotonated to give the neutral ketone.

Notes:

  • Acid is helpful but not an absolute requirement for this reaction. Reasonable mechanisms can be drawn without acid.
  • The “Cl” here in H3O+ Cl- is completely unimportant, just meant to show a balance of charge for H3O+. Other counter ions such as Br-, HSO3-, etc. would work just as well.
  • Note that this is an equilibrium reaction and goes in this direction because of the large excess of water. It is the exact reverse of imine formation.
  • There are certainly other reasonable ways to draw proton transfer (Step 3) and other species besides H2O that could conceivably act as bases in the last step.

{ 8 comments… read them below or add one }

Ivan December 7, 2012 at 6:07 pm

Great outline! Excellent helping me right before my exam!

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Emily December 10, 2012 at 8:37 pm

Great review, but I’m a little confused as to where the fifth carbon went on the intramolecular imine hydrolysis under examples?

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james December 11, 2012 at 4:43 pm

It’s a typo. Fixed – thanks for spotting it!

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Dani March 31, 2013 at 8:52 pm

Thanks this was really helpful!
Just one thing I’m still confused about… why can’t step 5 happen before step 4? Wouldn’t it be more favorable to deprotonate the oxygen first and then have the lone pair kick down and get rid of LG?

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james March 31, 2013 at 9:03 pm

Sure… but what’s going to deprotonate it? : – )
This is done under slightly acidic conditions.
Compare O-H (pka about 15) with protonated carbonyl (pKa -2)

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Karin January 12, 2014 at 1:19 pm

I’m not sure if this question belongs in this topic. But I’m just wondering is an iminium ion a stronger electrophile than an oxonium ion? It is in the Strecker synthesis, but I don’t exactly understand why.

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manjoorahmed September 20, 2014 at 4:15 am

hi,
is it possible to get imine from cyanide by making the use of grignard reagent?

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James September 23, 2014 at 11:24 am

Yes, but isolating the imine is not always very easy.

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