Aldol reaction

Not to be confused with Aldol reactions.
Aldol Addition
Reaction type Coupling reaction
Reaction
Ketone or Aldehyde
+
Ketone or Aldehyde
↓
β-hydroxy Aldehyde
or
β-hydroxy Ketone
Conditions
Temperature
-Δ, ~-70°C[a]
Catalyst
-OH or H+
Identifiers
Organic Chemistry Portal aldol-addition
RSC ontology ID RXNO:0000016

The aldol reaction (aldol addition) is a reaction in organic chemistry that combines two carbonyl compounds (e.g. aldehydes or ketones) to form a new β-hydroxy carbonyl compound. Its simplest form might involve the nucleophilic addition of an enolized ketone to another:

Prototype aldol reaction

These products are known as aldols, from the aldehyde + alcohol, a structural motif seen in many of the products. The use of aldehyde in the name comes from its history: aldehydes are more reactive than ketones, so that the reaction was discovered first with them.[2][3][4]

The aldol reaction is paradigmatic in organic chemistry and perhaps the most common means of forming carbon–carbon bonds in organic chemistry.[5][6][7] It lends its name to the family of aldol reactions and similar techniques analyze a whole family of carbonyl α-substitution reactions, as well as the diketone condensations. When the nucleophile and electrophile are different, the reaction is called a crossed aldol reaction; on the converse, when the nucleophile and electrophile are the same, the reaction is called an aldol dimerization.

Aldol structural units are found in many important molecules, whether naturally occurring or synthetic.[8][9] The reaction is used in several industrial syntheses, notably of pentaerythritol,[10] trimethylolpropane, the plasticizer 2-ethylhexanol, and the drug Lipitor (atorvastatin, calcium salt).[11] For many of the commodity applications, the stereochemistry of the aldol reaction is unimportant, but the topic is of intense interest for the synthesis of many specialty chemicals.

A typical experimental setup for an aldol reaction in a research laboratory.
The flask on the right is a solution of lithium diisopropylamide (LDA) in tetrahydrofuran (THF). The flask on the left is a solution of the lithium enolate of tert-butyl propionate (formed by addition of LDA to tert-butyl propionate). An aldehyde can then be added to the enolate flask to initiate an aldol addition reaction.
Both flasks are submerged in a dry ice/acetone cooling bath (−78 °C) the temperature of which is being monitored by a thermocouple (the wire on the left).
  1. ^ Klein, David R. (December 22, 2020). Organic chemistry (4th ed.). Hoboken, NJ: Wiley. p. 1014. ISBN 978-1-119-65959-4. OCLC 1201694230.
  2. ^ Cite error: The named reference Wurtz1872 was invoked but never defined (see the help page).
  3. ^ Cite error: The named reference Wurtz1872b was invoked but never defined (see the help page).
  4. ^ Cite error: The named reference Wurtz1872c was invoked but never defined (see the help page).
  5. ^ Wade, L. G. (2005). Organic Chemistry (6th ed.). Upper Saddle River, New Jersey: Prentice Hall. pp. 1056–66. ISBN 978-0-13-236731-8.
  6. ^ Smith, Michael B.; March, Jerry (2006). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. doi:10.1002/0470084960. ISBN 9780470084960.
  7. ^ Mahrwald, R. (2004). Modern Aldol Reactions, Volumes 1 and 2. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. pp. 1218–23. ISBN 978-3-527-30714-2.
  8. ^ Heathcock, C. H. (1991). "The Aldol Reaction: Acid and General Base Catalysis". In Trost, B. M.; Fleming, I. (eds.). Comprehensive Organic Synthesis. Vol. 2. Elsevier Science. pp. 133–179. doi:10.1016/B978-0-08-052349-1.00027-5. ISBN 978-0-08-052349-1.
  9. ^ Paterson, I. (1988). "New Asymmetric Aldol Methodology Using Boron Enolates". Chem. Ind. 12: 390–394.
  10. ^ Mestres R. (2004). "A green look at the aldol reaction". Green Chemistry. 6 (12): 583–603. doi:10.1039/b409143b.
  11. ^ Jie Jack Li; et al. (2004). Contemporary Drug Synthesis. Wiley-Interscience. pp. 118–. ISBN 978-0-471-21480-9.


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