Aldol reaction

An aldol reaction in the organic chemistry, catalyzed by acids or bases, the reaction of aldehydes or ketones. Aldol or aldolisation denotes the addition of an enolate or enolate anion as a nucleophile in a carbonyl component as the electrophile. This produces a β - hydroxy aldehyde or β - hydroxyketone. In an aldol condensation followed by elimination of water takes place and forms an α, β - unsaturated carbonyl. The aldol cleavage or retro-aldol reaction is the reverse reaction in the starting materials.

The name aldehyde - alcohol reaction is derived from the reaction product in the case of reaction with aldehydes, a β - hydroxy aldehyde from.

Aldol reactions are important reactions for the formation of carbon -carbon bonds and a basic principle of reaction in organic chemistry.

History

The aldol reaction was discovered in 1872 by Charles Adolphe Wurtz independently and Alexander Borodin Porfyrevich. Borodin has here the dimerization of acetaldehyde to 3- hydroxybutanal ( other names are aldol or acetaldol ) observed under acidic conditions.

Overview of reactions

Aldol and aldol condensation

In the course of aldol example, acetaldehyde reacts with another molecule of acetaldehyde to a β - hydroxy aldehyde - here: 3- hydroxybutanal, an aldol. In contrast, the product of a Aldolkonsensation same reactant (s ) is an α, β - unsaturated aldehyde - here: crotonaldehyde ( trans-2- butenal ). The reactions can take place both acids as well as base catalysis:

Instead of acetaldehyde, any ketones and aldehydes undergo such a reaction, if at least one of the reactants, an H- atom in α -position to the carbonyl group. The product of such aldol is a β - hydroxy aldehyde or a β -hydroxy ketone. Wherein the aldol condensation is formed, a α, β -unsaturated carbonyl compound ( aldehyde or ketone ).

Cross-aldol reaction

In a crossed or mixed aldol reaction of two carbonyl compounds with different organic radicals with each other. Do the reactants similar Carbonylaktivitäten, then a mixture of four different aldols arise:

Depending on the nature of R1 and R2 is - because of the formation of stereoisomers - the number of aldols formed exactly considered even higher. The cross-aldol reaction often proceeds unselective.

To minimize unwanted reactions between the various carbonyl compounds, strong bases should be used or appropriate reactants are selected. This gives sometimes less than four aldols when the reactivity of carbonyl compounds is different. For example, an aldehyde is more electrophilic than the ketone and thus reacts in a mixture of aldehyde and ketone carbonyl as the ketone reacts as enol, as this stabilizes the alkene because of the extra I effect an alkyl group. If one of the two carbonyl compounds used as starting material contains no α -hydrogen atoms - eg formaldehyde or benzaldehyde - runs the cross-aldol reaction uniformly. Such carbonyl compounds can not form enolates and therefore does not react with itself.

Particularly the cross-aldol reaction proceeds selectively when the ketone (for example acetone), at a low temperature with lithium diisopropylamide (LDA ) is converted into the lithium enolate, and a second carbonyl compound (e.g., acetaldehyde ) is reacted:

Stereoselectivity

In the aldol stereoselectivity can occur in the form of so -called simple diastereoselectivity. This means that the two pre- sp2 -hybridized carbon atoms ( and the enolate of the carbonyl component) which have a common binding in the product and form in each case a chiral center adopt mutually the same relative configuration. This will be explained using the Zimmerman -Traxler model of the transition state in which a pseudo- chair conformation is accepted.

Application

The aldol reaction is a very common procedure and has its application both on a laboratory scale as well as in the large-scale production.

The aldol reaction has gained great importance in the synthesis, especially of natural products. Closely related to the aldol reaction are name reactions such as the Claisen condensation, the Henry reaction and the Knoevenagel reaction. An asymmetric aldol reaction under mild conditions is the Hajos- Parrish -Eder -Sauer- Wiechert reaction.

A key step in the synthesis of atorvastatin, a heart drug from Pfizer, which was introduced in 1996, are two aldol reactions.

Biological Significance

The aldol reaction and its inverse are involved in many enzyme-catalyzed biochemical reactions to the change of the carbon skeleton of natural products. For example, the citrate from oxaloacetate and acetyl -CoA is formed in an aldol addition during aerobic carbohydrate degradation at the beginning of the citric acid cycle.

If the biosynthesis of isoprenoids via the mevalonic acid, then there is the combination of acetyl-CoA and acetoacetyl -CoA to 3-hydroxy -3-methylglutaryl -CoA an aldol reaction.

Gluconeogenesis in the two isomeric Ketotriosen glyceraldehyde-3- phosphate and dihydroxyacetone phosphate to react in the sense of an aldol reaction to fructose -1 ,6- bisphosphate.

The earlier assumption of Adolf von Baeyer and others that an aldol condensation is an important step of plant starch synthesis, is overtaken by more recent findings.