Aldol condensation

An aldol condensation is a condensation reaction in organic chemistry in which an enol or an enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), followed by dehydration to give a conjugated enone. An aldol condensation is a condensation reaction in organic chemistry in which an enol or an enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), followed by dehydration to give a conjugated enone. Aldol condensations are important in organic synthesis, because they provide a good way to form carbon–carbon bonds. For example, the Robinson annulation reaction sequence features an aldol condensation; the Wieland–Miescher ketone product is an important starting material for many organic syntheses. Aldol condensations are also commonly discussed in university level organic chemistry classes as a good bond-forming reaction that demonstrates important reaction mechanisms.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 or ketone having an α-hydrogen with an aromatic carbonyl compound lacking an α-hydrogen 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 ((1E, 4E)-1,5-diphenylpenta-1,4-dien-3-one). Quantitative yields in Claisen–Schmidt reactions have been reported in the absence of solvent using sodium hydroxide as the base and plus benzaldehydes. Because the enolizeable nucleophilic carbonyl compound and the electrophilic carbonyl compound are two different chemicals, the Claisen–Schmidt reaction is an example of a crossed aldol process. 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. Depending on the nature of the desired product, the aldol condensation may be carried out under two broad types of conditions: kinetic control or thermodynamic control. Crossed aldol condensation is a result of dissimilar carbonyl compounds containing α-hydrogen(s) undergoing aldol condensation. When 2 dissimilar carbonyl compounds react with each other, there are 4 possible products, they being due to: (a) Carbonyl compound 1 self condensation, or, (b) carbonyl compound 2 self condensation, or, (c) carbonyl compound 1 forming enolate ion and attacking the electrophilic centre of the other carbonyl compound, or, (d) vice-versa. If formation of a β-hydroxy carbonyl compound (aldol) having carbonyl compound 1 contribute as the electrophile in the mechanism is desired, then, it being provided that the said compound does not have an α-hydrogen, the said compound is mixed with a suitable base and another carbonyl compound is slowly added to the said mixture. It must be noted that the concentration of the base must not be to high, nor should the base be too strong, as, if the carbonyl compound 1 is an aldehyde, Cannizaro reaction may result. Crossed aldol condensation between 2 dissimilar aldehydes containing α-hydrogens is rarely attempted as a synthetically useless mixture is formed, comprising 4 aldol products. The above-mentioned case may be referred to when it comes to significant crossed aldol product between two aldehydes, with one not possessing any α-hydrogens. Any crossed aldol condensation between 2 ketones is useless, as the it is useful somuch as it can cause problems for reproductive system so be careful while using equilibrium lies far to the left. In the aldol condensation between an aldehyde and a ketone, the ketone acts as the nucleophile, as its carbonyl carbon, due to +I effect and steric hindrance, does not possess high electrophilic character. Usually, the crossed product is the major one. Any traces of the self-aldol product (that between 2 molecules of the aldehyde itself) may be disallowed to form by first preparing a mixture of a suitable base and the ketone and then adding the aldehyde slowly to the said reaction mixture. It is important to distinguish the aldol condensation from other addition reactions of carbonyl compounds. In industry the Aldox process developed by Royal Dutch Shell and Exxon, converts propene and syngas directly to 2-ethylhexanol via hydroformylation to butyraldehyde, aldol condensation to 2-ethylhexenal and finally hydrogenation. In one study crotonaldehyde ((2E)-but-2-enal) is directly converted to 2-ethylhexanal in a palladium / Amberlyst / supercritical carbon dioxide system: