Enamine Hydrolysis

by James

Description: Enamines are hydrolyzed to ketones/aldehydes by treatment with aqueous acid. This is often performed after the Stork enamine reaction.

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Notes: Acid catalyst here is sometimes just written as H+/H2O, or “aqueous acid”, or H3O+, or H2SO4/H2O ; there are many ways of depicting the same thing. A secondary amine is released as well as the ketone/aldehyde. Note that the oxygen of the ketone/aldehyde comes from water.

Examples:

2-examplesNotes: Note that “aqueous acid” can be shown several different ways. If a stereocenter is formed (as it is in example 3) it will be formed as a racemic mixture. Hydrolysis of examines is common after the Stork enamine reaction, of which Example 3 could be an example.

Mechanism: Hydrolysis of examines is the exact opposite of their formation! In the first step, protonation on carbon (Step 1, arrows A, B, and C) leads to an iminium ion. Addition of water to the iminium ion (Step 2, arrows D and E) leads to a protonated “hemiaminal”, which then undergoes proton transfer (Step 3, arrows F/G and Step 4, arrows H/I) to give the ammonium ion, which then undergoes elimination (Step 5, arrows J and K). This is then deprotonated by weak base (Step 6, arrows L and M) to give the neutral ketone.

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Notes: Note that sometimes the proton transfer step (steps 3 and 4) can be shown as a single step. Also the exact identity of the base used to deprotonated in step 6 is not crucial – there are many species in solution basic enough to remove this proton (such as water, counter-ion of acids, etc). This is just one possibility.

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