Aldol condensation
المؤلف:
University of Missouri System
المصدر:
Organic Chemistry ii
الجزء والصفحة:
.................
13-10-2020
4084
Aldol condensations are important in organic synthesis, because they provide a good way to form carbon–carbon bonds. In its usual form, it involves the nucleophilic addition of a ketone enolate to an aldehyde to form a β-hydroxy ketone, or “aldol” (aldehyde + alcohol), a structural unit found in many naturally occurring molecules and pharmaceuticals.
The name aldol condensation is also commonly used, especially in biochemistry, to refer to just the first (addition) stage of the process—the aldol reaction itself—as catalyzed by aldolases. However, the aldol reaction is not formally a condensation reaction because it does not involve the loss of a small molecule.
The reaction between an aldehyde/ketone and an aromatic carbonyl compound lacking an alpha-hydrogen (cross aldol condensation) is called the Claisen-Schmidt condensation. This reaction is named after two of its pioneering investigators Rainer Ludwig Claisen and J. G. Schmidt, who independently published on this topic in 1880 and 1881. An example is the synthesis of dibenzylideneacetone. Quantitative yields in Claisen-Schmidt reactions have been reported in the absence of solvent using sodium hydroxide as the base and plus benzaldehydes.
Mechanism
The first part of this reaction is an aldol reaction, the second part a dehydration—an elimination reaction (Involves removal of a water molecule or an alcohol molecule). Dehydration may be accompanied by decarboxylation when an activated carboxyl group is present. The aldol addition product can be dehydrated via two mechanisms; a strong base like potassium t-butoxide, potassium hydroxide or sodium hydride in an enolate mechanism, or in an acid-catalyzed enol mechanism. We will focus on the base-catalyzed mechanism, which is more widely used.
Enolate mechanism
If the catalyst is a moderate base such as hydroxide ion or an alkoxide, the aldol reaction occurs via nucleophilic attack by the resonance-stabilized enolate on the carbonyl group of another molecule. The product is the alkoxide salt of the aldol product. The aldol itself is then formed, and it may then undergo dehydration to give the unsaturated carbonyl compound. The scheme shows a simple mechanism for the base-catalyzed aldol reaction of an aldehyde with itself.
Base-catalyzed aldol reaction (shown using −OCH3 as base)
Base-catalyzed dehydration
Although only a catalytic amount of base is required in some cases, the more usual procedure is to use a stoichiometric amount of a strong base such as LDA. In this case, enolate formation is irreversible, and the aldol product is not formed until the alkoxide of the aldol product is protonated in a separate acid-base workup step. Mixtures of stereoisomers (E & Z) are obtained from some reactions, though the E product is generally favored. Overall the general reaction involves a dehydration of an aldol product to form an alkene:
Going from reactants to products simply 
Figure: The aldol condensation example
Example 2: Aldol Condensation
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