Aldol addition reaction of aldehydes and ketones

by James

Description: The Aldol reaction is the addition of an enolate ion with an aldehyde or ketone.
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Notes: 

  • The reaction is called called an aldol reaction since the product in the above case contains both an aldehyde and an alcohol.
  • The enolate ion is formed through deprotonation of an aldehyde or ketone with strong base.
  • When  two different aldehydes (or ketones) are used it is called a  “crossed” aldol reaction.
  • When the reaction is heated, a molecule of water can be eliminated from the product, resulting in formation of a new alkene. This is called the “aldol condensation”.

Examples:

Notes: The first example shows a crossed aldol. Note how only one of the aldehydes can form an enolate ion, so the only “crossed aldol” product possible is the one depicted. Likewise in the second case.

The third case shows another way to do a crossed aldol. The use of the strong base lithium diisopropylamide (LDA) leads to selective formation of the less substituted enolate, which can then attack the aldehyde when added.

Mechanism:

The reaction begins with deprotonation of the aldehyde (or ketone) (Step 1, arrows A and B) which gives an enolate ion. The enolate then attacks the carbonyl carbon of a second aldehyde in a 1,2-addition reaction (Step 2, arrows C and D). The product is then protonated on the oxygen (Step 3, arrows E and F) to give the aldol addition product.

 Notes:

Note that as drawn the reaction is catalytic in NaOH. There’s nothing particularly special about the Na here, other salts of hydroxide ion (e.g. KOH or LiOH) perform admirably. It’s also reasonable to use another equivalent of aldehyde/ketone as the acid instead of water.

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{ 4 comments… read them below or add one }

James

Hi,
I am slightly confused about the first two examples as it seems that the enolate formed from the least substituted carbonyl compound without the use of LDA?
Many thanks for an excellent website.

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james

Aha! Look more closely… what enolates are possible here?

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Petr Menzel

Hi, is there possibility to use Na2CO3 like a base? What would be different? Thx, P.

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James

Sure, one could use Na2CO3 as a base – it’s probably reacting with water present in solution to give trace amounts of HO- , which is doing the deprotonation. Na2CO3 isn’t the greatest base in the world however.

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