Aldol Condensation

by James

Description: The aldol condensation is a reaction between an enolate (or enol) and an aldehyde or ketone that leads to the formation of a new carbon-carbon double bond. This is the product if an aldol addition reaction is heated for prolonged periods. The reaction is called a “condensation” because one molecule of water is formed from the two reactants.
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Notes: Although base is shown here, the reaction can also be catalyzed by acid.

Examples:

Notes: Example 3 shows an instance where acid is used as the catalyst. Examples 2 and 3 show “crossed” aldol reactions – that is, a reaction between two different aldehydes or ketones. In these cases only one of the two aldehydes has a carbon adjacent to the carbonyl (“alpha-carbon”) that contains a C-H bond; therefore only one enolate can be formed.
Elimination reactions are favored by heat; that is what distinguishes  this from the aldol addition reaction.
Example 4 shows an intramolecular aldol condensation.

Mechanism: Deprotonation of the aldehyde alpha carbon (Step 1, arrows A and B) leads to formation of an enolate, which attacks the carbonyl carbon in an addition reaction (Step 2, arrows C and D). Protonation of the oxygen (Step 3, arrows E and F) followed by subsequent deprotonation of the carbon adjacent to the carbonyl (Step 4, arrows G and H) leads to an enolate, which then eliminates hydroxide ion (HO-) forming an alkene.

Notes: The final elimination step can also be drawn this way (using the resonance form of the enolate):

For the mechanism of the acid-catalyzed version, see this post.

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{ 6 comments… read them below or add one }

David Carnevale

Are there any conditions in which the ketone and alcohol remain and the double bond does not form in the final elimination step?

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James

Yes – that’s “aldol addition”. Typically one avoids using heat in that process.

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Petr Menzel

Hi, is the “heat” always important? Or can I use another way for condensation? Thx, P.

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James

Hi Petr – for aldol condensation, heat tends to favour elimination of water. If one wants to perform the aldol condensation, the best way to go about it is to heat the reaction mixture. To avoid the elimination, and to just perform an aldol addition reaction, typically one uses lower temperatures.

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Rich Aversa

In the intramolecular reaction, the ketone you deprotonated has a primary and a secondary alpha carbon, so it has two different enolate forms. The conditions used would encourage formation of the “thermodynamic enolate”, i.e. the more substituent pi bond. Thus, the cyclic product would look quite different. For instance the remaining ketone would not “straddle” the ring but “hang off”, connected to its now tertiary alpha carbon. As I’ve seen it in other sources, a 1,6-diketone should yield a five-membered ring. Is this correct?

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James

While that enolate is in fact the more stable “thermodynamic” enolate, it would form a 4-membered ring, not a 5-membered ring. That’s why it doesn’t happen.

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