In aldol addition reactions, an enolate and aldehyde react to create the aldol addition product.
An aldol is a molecule formed from the reaction of an enolate with a carbonyl and is composed of a carbonyl and an alcohol. In an aldol addition reaction, aldehydes and/or ketones are treated with a base to yield a solution containing a carbonyl compound and its enolate, which combine through the formation of a C−C bond. An enolate is the anion formed when the alpha hydrogen is removed as a hydrogen ion. The product of the aldol addition is a beta-hydroxy aldehyde. The name aldol is a combination of aldehyde and alcohol. The resultant molecule contains components from both of these compounds.
Aldol Addition
An aldol addition reaction results in the formation of a beta-hydroxy aldehyde.
The mechanism of the aldol addition proceeds through three steps:
1. The aldehyde or ketone is converted to its enolate by abstraction, which is the removal of a proton by a base.
2. The enolate, acting as a nucleophile, is added to the carbonyl group.
3. A proton is abstracted by the alkoxide product in Step 2 from water to make the aldol.
Mechanism of Aldol Addition
The mechanism of aldol addition involves three steps. Step 1 is the formation of an enolate. Step 2 is the nucleophilic attack of the enolate on a carbonyl group. Step 3 is the protonation of the resulting alkoxide to form the aldol product.
When heated, the products of the aldol addition dehydrate, resulting in alpha,beta-unsaturated aldehydes. This is an aldol condensation reaction, which is an aldol addition wherein the beta-hydroxy aldehyde or ketone dehydrates. An alpha,beta-unsaturated molecule has a π bond between the alpha (α) and beta (β) carbons attached to a carbonyl group. A condensation reaction is a chemical reaction that combines two molecules together with the elimination of a water molecule.
Aldol Condensation
When heat adds to the products of an aldol addition, dehydration results in formation of alpha,beta-unsaturated aldehydes.
Crossed and Intramolecular Aldol Addition
Crossed aldol addition reactions are when two different carbonyls mix to form an aldol product. The carbonyls are mixed at the same time (practical) or mixed stepwise (directed). If the two carbonyls are part of the same molecule, an intramolecular aldol reaction occurs.
In a practical crossed aldol reaction, two different carbonyl compounds mix together, and only one can form an enolate, preventing self-condensation of the other compound.
A directed aldol reaction is a reaction in which the enolate is prepared in the first step and the intended reactant is added in the second step to ensure the desired product. In a directed aldol addition, a strong base, such as lithium diisopropylamide (LDA), causes immediate formation of the enolate, and then the compound intended to react to the enolate adds, ensuring the desired product.
Directed Aldol Addition
Use of a directed aldol reaction ensures that the desired compound forms by producing enolate in the first step and adding the compound intended to react in a second step.
An intramolecular aldol reaction can occur when a molecule has two aldehydes or two ketones or an aldehyde and a ketone separated by enough carbons to make a five- or six-membered ring. An intramolecular aldol reaction is a reaction in which the enolate and carbonyl components are parts of a single molecule. Intramolecular aldol reactions favor formation of a more stable five- or six–membered ring.
Intramolecular Aldol Reaction
Intramolecular aldol reactions occur in large molecules that contain both an enolate and a carbonyl component and favor formation of a five- or six-membered ring.
A retro-aldol reaction is the reverse of an aldol reaction. It decomposes a beta-hydroxy carbonyl into an aldehyde or ketone and another carbonyl compound.
Retro-Aldol Reaction
Early in glycolysis, a retro-aldol reaction catalyzed by aldolase converts D-fructose 1,6-diphosphate to D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
