Aldol condensation

An Aldol condensation is an enone.

Aldol condensations are important in aldehyde to form a β-hydroxy ketone, or "aldol" (aldehyde + alcohol), a structural unit found in many naturally occurring molecules and pharmaceuticals.^[4]^[5]^[6]

The name aldol condensation is also commonly used, especially in condensation reaction because it does not involve the loss of a small molecule.

The reactions between a ketone and an aldehyde (crossed aldol condensation) or between two aldehydes also go by the name Claisen-Schmidt condensation. These reactions are named after two of its pioneering investigators dibenzylideneacetone.

Mechanism

The first part of this reaction is an enol mechanism.

Condensation types

It is important to distinguish the Aldol condensation from other addition reactions to carbonyl compounds.

When the base is an amine and the active hydrogen compound is sufficiently activated the reaction is called a Knoevenagel condensation.
In a Perkin reaction the aldehyde is anhydride.
A ester compounds.
A Dieckmann condensation involves two ester groups in the same molecule and yields a cyclic molecule
A nitro compound.
A Michael reaction prior to the aldol condensation.
In the Guerbet reaction, an aldehyde, formed in situ from an alcohol, self-condenses to the dimerized alcohol.

Aldox process

In industry the Aldox process developed by Royal Dutch Shell and hydrogenation ^[11].

In one study Amberlyst / supercritical carbon dioxide system ^[12]:

Scope

Ethyl 2-methylacetoacetate and campholenic aldehyde react in an Aldol condensation.^[13] The synthetic procedure ^[14] is typical for this type of reactions. In the process in addition to water, an equivalent of ethanol and carbondioxide are lost in decarboxylation.

cis-dienoid structure.^[15]

Occasionally an aldol condensation is buried in a multistep reaction or in catalytic cycle such as the one sketched below:^[16]

In this reaction an alkynal 1 is converted into a cycloalkene 7 with a isotope labeling.^[17]

The reaction between DMSO in the reaction below ^[18]:

Due to epimerization through a common cis configuration and not (R,S) trans as in the starting material. Because it is only the cis isomer that precipitates from solution this product is formed exclusively.

References

^ Wade, L. G. (6th ed. 2005). Organic Chemistry. Upper Saddle River, New Jersey: Prentice Hall, 1056-1066. ISBN 0132367319.
^ Smith, M. B.; March, J. (5th ed. 2001). Advanced Organic Chemistry. New York: Wiley Interscience, 1218-1223. ISBN 0-471-58589-0.
^ Mahrwald, R. (2004). Modern Aldol Reactions, Volumes 1 and 2. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 1218-1223. ISBN 3-527-30714-1.
^ Heathcock, C. H. (1991). Comp. Org. Syn.. Oxford: Pergamon, 133-179. ISBN 0-08-040593-2.
^ Mukaiyama T. (1982). "The Directed Aldol Reaction". Org. React. 28: 203-331.
^ Paterson, I. (1988). "New Asymmetric Aldol Methodology Using Boron Enolates". Chem. Ind. 12: 390-394.
^ L. Claisen and A. Claparede, Ber. 14, 2460 (1881)
^ J. G. Schmidt, Ber. 14,1459 (1881)
^ Advanced organic Chemistry, Reactions, mechanisms and structure 3ed. Jerry March ISBN 0-471-85472-7
^ Nielsen, A. T.; Houlihan., W. J. Org. React. 1968, 16, 1-438. (Review)
^ For example BG patent 881979
^ Continuous catalytic ‘‘one-pot’’ multi-step synthesis of 2-ethylhexanal from crotonaldehyde Tsunetake Seki, Jan-Dierk Grunwaldt and Alfons Baiker Chem. Commun., 2007, 3562–3564 doi:10.1039/b710129e DOI: 10.1039/b710129e
^ (E)-6-(2,2,3-Trimethyl-cyclopent-3-enyl)-hex-4-en-3-one Concepcion Bada, Juan M. Castro, Pablo J. Linares-Palomino, Sofia Salido, Joaquan Altarejos Manuel Nogueras, Adolfo Sanchez, Molbank 2004, M388 Online Publication
^ Ethyl 2-methylacetoacetate (2) is added to a stirred solution of vacuum distillation to give 3 (58%).
^ M. B. Goren, E. A. Sokoloski and H. M. Fales (2005). "2-Methyl-(1Z,3E)-butadiene-1,3,4-tricarboxylic Acid, "Isoprenetricarboxylic Acid"". J. Org. Chem. 70 (18): 7429-7431. doi:10.1021/jo0507892.
^ J. A. Varela, C. Gonzalez-Rodriguez, S. G. Rubin, L. Castedo and C. Saa (2006). "Ru-Catalyzed Cyclization of Terminal Alkynals to Cycloalkenes". J. Am. Chem. Soc. 128 (30): 9576-9577. doi:10.1021/ja0610434.
^ The reductive elimination to form the cycloalkene.
^ Simple and Effective Protocol for Claisen-Schmidt Condensation of Hindered Cyclic Ketones with Aromatic Aldehydes Valeriy Vashchenko, Lidiya Kutulya, Alexander Krivoshey Synthesis 2007: 2125-2134 doi:10.1055/s-2007-983746

Condensation reactions

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Aldol_condensation". A list of authors is available in Wikipedia.