Aldol reaction
In organic chemistry, an aldol reaction is a reaction of aldehydes or ketones catalyzed by acids or bases . Aldol addition or aldolization refers to the addition of an enolate or enolation as a nucleophile to a carbonyl component as an electrophile . This creates a β-hydroxyaldehyde or β-hydroxyketone. In the case of an aldol condensation , water is then eliminated and an α, β-unsaturated carbonyl is formed. The aldol cleavage or retroaldol reaction is the reverse reaction into the starting compounds.
The name Ald ehyd alcoh- ol reaction is derived from the reaction product in case of a reaction with aldehydes, a β-hydroxy aldehyde , from.
Aldol reactions are important reactions for the formation of carbon-carbon bonds and a fundamental reaction principle in organic chemistry.
history
The aldol reaction was discovered independently by Charles Adolphe Wurtz and Alexander Porfyrevich Borodin in 1872. Borodin has observed the dimerization of acetaldehyde to 3-hydroxybutanal (other names are aldol or acetaldol) under acidic conditions.
Overview reactions
Aldol addition and aldol condensation
In the course of an aldol addition, for example, acetaldehyde reacts with another molecule of acetaldehyde to form a β-hydroxyaldehyde - here: 3-hydroxybutanal , an aldol . In contrast, the product of an aldol condensation of the same starting material (s) is an α, β-unsaturated aldehyde - here: crotonaldehyde ( trans -2-butenal). The reactions can take place with either acid or base catalysis:
Instead of the acetaldehydes, any ketones and aldehydes can enter into such a reaction if at least one of the starting materials has an H atom in the α-position to the carbonyl group. The product of such an aldol addition is a β-hydroxyaldehyde or a β-hydroxyketone. During the aldol condensation, an α, β-unsaturated carbonyl compound (aldehyde or ketone) is formed.
Crossed aldol reaction
In a crossed or mixed aldol reaction, two carbonyl compounds with different organic radicals react with one another. If the starting materials have similar carbonyl activities, a mixture of four different aldols can result:
Depending on the nature of the radicals R 1 and R 2 - because of the formation of stereoisomers - the number of aldols formed is even higher, if considered more closely. The crossed aldol reaction is often unselective.
In order to minimize unwanted reactions between the different carbonyl compounds, strong bases must be used or appropriate starting materials must be selected. Sometimes fewer than four aldols are obtained if the reactivity of the carbonyl compounds is different. For example, an aldehyde is more electrophilic than a ketone and thus reacts in a mixture of aldehyde and ketone as a carbonyl component, while the ketone reacts as an enol, as this stabilizes the alkene due to the additional + I effect of an alkyl group . If one of the two carbonyl compounds used as starting material contains no hydrogen atoms in the α position - z. B. formaldehyde or benzaldehyde - the crossed aldol reaction proceeds uniformly. Such carbonyl compounds cannot form enolates and therefore cannot react with themselves.
The cross-aldol reaction proceeds particularly selectively if the ketone (e.g. acetone ) is converted into lithium enolate with lithium diisopropylamide (LDA) at low temperature and reacted with a second carbonyl compound (e.g. acetaldehyde):
Stereoselectivity
In the case of aldol addition, stereoselectivity can occur in the form of what is known as simple diastereoselectivity . This means that the two previously sp 2 -hybridized carbon atoms (of the enolate and the carbonyl component), which have a common bond in the product and each form a stereocenter , have the same relative configuration to one another. This is explained using the Zimmerman-Traxler model of the transition state, in which a pseudo-chair conformation is assumed.
application
The aldol reaction is a very widespread process and is used both on a laboratory scale and in large-scale production.
The aldol reaction has gained great importance in synthesis , especially of natural products . Name reactions such as the Claisen condensation , the Henry reaction and the Knoevenagel reaction are closely related to the aldol reaction . An asymmetric aldol reaction under mild conditions is the Hajos-Parrish-Eder-Sauer-Wiechert reaction .
Biological importance
The aldol reaction and its reversal are involved in many enzymatically catalyzed biochemical reactions in changing the carbon structure of natural products. For example, in aerobic carbohydrate breakdown at the beginning of the citric acid cycle, the citrate is formed from oxaloacetic acid and acetyl-CoA in an aldol addition.
If the biosynthesis of the isoprenoids takes place via the mevalonic acid , then the linkage of acetyl-CoA and acetacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA is an aldol reaction.
During gluconeogenesis , the two isomeric ketotrioses glyceraldehyde-3-phosphate and dihydroxyacetone phosphate react in the form of an aldol reaction to form fructose-1,6-bisphosphate.
The earlier assumption by Adolf von Baeyer and others that an aldol condensation is an important step in plant starch synthesis is outdated by more recent findings.
literature
- Thomas Laue, Andreas Plagens: Name and catchword reactions in organic chemistry. 5th revised edition, unchanged reprint, Vieweg + Teubner, Wiesbaden 2009, ISBN 978-3-8351-0091-6 .
- Jürgen Falbe, Manfred Regitz (ed.): Römpp compact basic lexicon chemistry. Thieme, Stuttgart a. a. 1998, ISBN 3-13-115711-9 .
Web links
Individual evidence
- ↑ Joachim Buddrus: Fundamentals of organic chemistry . 4th revised and updated edition, Walter de Gruyter, Berlin / New York 2011, ISBN 978-3-11-024894-4 , p. 616 ff.
- ↑ Ulrich Lüning: Organic reactions . 2nd edition, Elsevier, Munich 2007, ISBN 978-3-8274-1834-0 , p. 114.
- ↑ a b Joachim Buddrus: Fundamentals of organic chemistry . 4th edition, de Gruyter, Berlin / New York 2011, ISBN 978-3-11-024894-4 , pp. 620–622.