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.

{ 15 comments… read them below or add one }

Ivan

Great outline! Excellent helping me right before my exam!

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Emily

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

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

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Dani

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

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

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

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

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James

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

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P. Naveen kumar

Imines are not stable it will undergo hydrolysis to get carbonyl compounds

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Alen

I don’t quite get it. Isn’t H2O a better leaving group then NH3 or in other words, isn’t the latter a better nucleophile? Why does then reaction proceed towards the ketone? Just because water is in excess?
Thank you for the clarification in advance…

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James

Yes – the reaction is in equilibrium, but the high concentration of H2O pushes the reaction toward the hydrolysis product.

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Alen

Thank you for your fast reply. Let me just say that this site is exceptionally educational and helpful!
Cheers…

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jeroen

Hello,

I want to transfer carvone semicarbazone (an imine of carvone) back to carvone using this reaction. Which concentrations are suitable to do this? Is it reasonable to use 0,1 M HCl for example?

In other words: at wich pH has the reaction maxiumum efficiency?

Kind regards
Jeroen Vandervelde

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Mahfuzul Hoque

Hi
Thanks for the nice illustration.
My query is after removal of water is the resultant imine air stable?

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James

Air stable? Absolutely. However in the presence of water it will hydrolyze.

Reply

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