Aldol condensation

Source: Wikipedia, the free encyclopedia.
Aldol condensation
Reaction type Condensation reaction
Reaction
Ketone or Aldehyde
+
Ketone or Aldehyde
α,β-unsaturated Aldehyde
or
α,β-unsaturated Ketone
Conditions
Temperature
+Δ, ~100°C[a]
Catalyst
OH or H+
Identifiers
Organic Chemistry Portal aldol-condensation
RSC ontology ID RXNO:0000017

An aldol condensation is a

enone
.

The overall reaction equation is as follows (where the Rs can be H) Aldol condensation overview

Aldol condensations are important in organic synthesis and biochemistry as ways to form carbon–carbon bonds.[2][3][4][5]

In its usual form, it involves the

pharmaceuticals.[6][7][8]

The Aldol reaction
The Aldol reaction

The term aldol condensation is also commonly used, especially in

aldolases. However, the first step is formally an addition reaction
rather than a condensation reaction because it does not involve the loss of a small molecule.

Mechanism

The first part of this reaction is an

Both ketones and aldehydes are suitable for aldol condensation reactions. In the examples below, aldehydes are used.

Base-catalyzed aldol condensation

A mechanism for aldol condensation in basic conditions, which occurs via enolate intermediates and E1CB elimination.
A mechanism for aldol condensation in basic conditions, which occurs via enolate intermediates and E1CB elimination.

Acid-catalyzed aldol condensation

A mechanism for aldol condensation in acidic conditions, which occurs through enol intermediates and an elimination reaction.
A mechanism for aldol condensation in acidic conditions, which occurs through enol intermediates and an elimination reaction.
Animation zum basenkat. Reaktionsmechanismus der Aldolkondensation Animation zum säurekat. Reaktionsmechanismus der Aldolkondensation
animation, base catalyzed animation, acid catalyzed

Crossed aldol condensation

A crossed aldol condensation is a result of two dissimilar carbonyl compounds containing α-hydrogen(s) undergoing aldol condensation. Ordinarily, this leads to four possible products as either carbonyl compound can act as the nucleophile and self-condensation is possible, which makes a synthetically useless mixture. However, this problem can be avoided if one of the compounds does not contain an α-hydrogen, rendering it non-enolizable. In an aldol condensation between an aldehyde and a ketone, the ketone acts as the nucleophile, as its carbonyl carbon does not possess high electrophilic character due to the

steric hindrance. Usually, the crossed product is the major one. Any traces of the self-aldol product from the aldehyde may be disallowed by first preparing a mixture of a suitable base and the ketone and then adding the aldehyde slowly to the said reaction mixture. Using too concentrated base could lead to a competing Cannizzaro reaction.[12]

Examples

The Aldox process, developed by

2-ethylhexanol via hydroformylation to butyraldehyde, aldol condensation to 2-ethylhexenal and finally hydrogenation.[13]

Aldox process

Pentaerythritol is produced on a large scale beginning with crossed aldol condensation of acetaldehyde and three equivalents of formaldehyde to give pentaerythrose, which is further reduced in a Cannizzaro reaction.[14]

Pentaerythritol Synthesis

Scope

Ethyl 2-methylacetoacetate and campholenic aldehyde react in an Aldol condensation.[15] The synthetic procedure[16] is typical for this type of reaction. In the process, in addition to water, an equivalent of ethanol and carbon dioxide are lost in decarboxylation.

Aldol condensation of Ethyl 2-methylacetoacetate and campholenic aldehyde.

methyl group and the carboxylic group in the cis-dienoid structure.[17]

Isoprenetricarboxylic acid
Isoprenetricarboxylic acid

Occasionally, an aldol condensation is buried in a multistep reaction or in catalytic cycle as in the following example:[18]

Ru Catalyzed Cyclization of Terminal Alkynals to Cycloalkenes
Ru Catalyzed Cyclization of Terminal Alkynals to Cycloalkenes

In this reaction an alkynal 1 is converted into a

isotope labeling.[b]

The reaction between

steric shielding of the ketone group. This obstacle is overcome by using a strong base such as potassium hydroxide and a very polar solvent such as DMSO in the reaction below:[19]

A Claisen–Schmidt reaction
A Claisen–Schmidt reaction

The product can

equilibrium reaction
to form this as the major product.

Other condensation reactions

There are other reactions of carbonyl compounds similar to aldol condensation:

See also

References

  1. .
  2. .
  3. ^ .
  4. .
  5. .
  6. .
  7. .
  8. ^ Paterson, I. (1988). "New Asymmetric Aldol Methodology Using Boron Enolates". Chemistry and Industry. 12. London: Paterson Group: 390–394.
  9. .
  10. .
  11. .
  12. .
  13. ^ Graduated hydrogenation of aldox aldehydes to alcohols US US3118954A 
  14. ; Collected Volumes, vol. 1, p. 425.
  15. .
  16. dioxane. Then campholenic aldehyde (1) is added and the mixture refluxed for 15 h. Then 2N hydrochloric acid is added and the mixture extracted with diethyl ether. The combined organic layers are washed with 2N hydrochloric acid, saturated sodium bicarbonate and brine. The organic phase is dried over anhydrous sodium sulfate and the solvent evaporated under reduced pressure to yield a residue that is purified by vacuum distillation
    to give 3 (58%).
  17. .
  18. .
  19. .

Notes

  1. aldol addition side product would be formed alongside the aldol condensation product.[1]
  2. chemical yield. The first step is formation of the Transition metal carbene complex 2. Acetic acid adds to this intermediate in a nucleophilic addition to form enolate 3 followed by aldol condensation to 5 at which stage a molecule of carbon monoxide is lost to 6. The final step is reductive elimination
    to form the cycloalkene.

External links