20.7.1. Review: Preparation of enolates
The enolate has two resonance forms: the negative charge can be on carbon or oxygen, but enolates generally react as carbon nucleophiles, as we saw.Section 9.7. with enolate S alkylationnorte2 reactions.
When we studied the chemistry of the enolate beforeSection 9.7we used LDA to generate enolates, which were then used as nucleophiles in Snorte2 reactions. For these alkylation reactions to be useful, the enolate anions must be generated in high concentration in the absence of other nucleophiles and strong bases. Aqueous base (eg, aq. NaOH) and alkoxides (eg, NaOCH2CH3) are generally unsuitable because they produce only low concentrations of the enolate anions and the remaining -OH or -OR can cause unwanted side reactions. In other words, these nucleophilic bases simply react directly with the alkyl halide through an Snorte2 reaction.
If the enolate formed is stabilized with more than one carbonyl, it is possible to use a weaker base, such as sodium ethoxide, to form the enolate almost quantitatively.
NaOCH2CH3= that+ –mi2CH3= NaOEt
Enolates are very useful in synthesis because they are a stabilized nucleophilic form of carbon. This diagram shows the range of reactions that can be used:
Next, we look at the aldol reaction. The Claisen condensation is discussed later inSection 22.2.
20.7.2. basic aldol reaction
general aldol reaction
When a base is added to an aldehyde or ketone containing an alpha hydrogen at low temperatures, an enolate is formed which immediately undergoes nucleophilic addition via the C=O of another aldehyde or ketone molecule. While the reaction is kept cool, a beta hydroxy aldehyde (often referred to as an "aldol") or beta hydroxy ketone product can be isolated. Since the only electrophile present is the aldehyde/ketone, a weaker base such as NaOH or NaOCH3It can be used.
When the reaction is heated, it can lose a molecule of water to form an alkene aldehyde or alkene ketone known as an alpha-, beta-aldehyde, or unsaturated ketone. In this case, the overall response is known as inaldol condensation.
aldol condensation
Aaldol condensationis a condensation reaction in organic chemistry in which an enol or enolate ion reacts with a carbonyl compound to form a β-hydroxy aldehyde or β-hydroxyketone, followed by dehydration to give an enone conjugate.
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-hydroxyketone or "Aldol”(alternativepure + alcoholHola), a structural unit found in many natural pharmaceuticals and molecules.
Namealdol condensationit is also commonly used, especially in biochemistry, to refer only to the first step (addition) of the process, the aldol reaction itself, catalyzed by aldolases. However, the aldol reaction is not formally a condensation reaction, since it does not involve the loss of a small molecule.
The reaction between an aldehyde/ketone and an aromatic carbonyl compound without an alpha hydrogen (aldol cross condensation) is called a reaction.Claisen-Schmidt condensation. This reaction is named after two of its pioneering researchers, Rainer Ludwig Claisen and J.G. Schmidt, who independently published on the subject in 1880 and 1881. An example is the synthesis of dibenzylideneacetone. Quantitative yields have been reported in Claisen-Schmidt reactions in the absence of solvent using sodium hydroxide as the base plus benzaldehydes.
Mechanism
The first part of this reaction is an aldol reaction, the second part is dehydration, an elimination reaction (involves removing either a water molecule or an alcohol molecule). Dehydration can be accompanied by decarboxylation when an activated carboxyl group is present. The aldol addition product can be dehydrogenated via two mechanisms; a strong base such as potassiumT-butoxide, potassium hydroxide or sodium hydride in an enolate mechanism or in an acid-catalyzed enol mechanism. We focus on the base-catalyzed mechanism, which is more widespread.
enolate mechanism
yes orCatalystis a moderate base likeHydroxideion o onealkoxide, the aldol reaction occurs through nucleophilic attack bystabilized resonanceEnolate on the carbonyl group of another molecule. the product is thealkoxidesalt of the aldol product. The aldol itself is then formed and can then be subjected to dehydration to give the unsaturated carbonyl compound. The schematic shows a simple mechanism for the base-catalyzed aldol reaction of an aldehyde with itself.
base catalyzed aldol reaction(shown with−mi3as a basis)
base catalyzed dehydration
Although in some cases only a catalytic amount of base is required, the most common method is to use astoichiometricamount of a strong base, such asLDA. In this case, enolate formation is irreversible and the aldol product is not formed until the alcoholate of the aldol product is protonated in a separate acid-base processing step. Mixtures of stereoisomers (E and Z) are obtained from some reactions, although product E is generally preferred. In general, the general reaction involves dehydration of an aldol product to form an alkene:
Simply from reactants to products
Figure: The example of aldol condensation
Example 2: Aldol condensation
intramolecular aldol reaction
Molecules containing two carbonyl functionalities have the potential to form a ring through an intramolecular aldol reaction. Here the “head” of the molecule “bites its tail”. In most cases, two sets of hydrogen atoms [latex] α [/latex] must be considered. As with most ring-forming reactions, five- and six-membered rings are preferred.
As in other aldol reactions, the addition of heat causes aldol condensation.
Mixed aldol reaction and condensations.
The previous examples of aldol reactions and condensations used a common reagent as both an enol donor and an electrophilic acceptor. The product in such cases is always a dimer of the carbonyl compound of the reaction. aldol condensations between different carbonyl reactantscrossedomixedreactions, and under certain conditions such aldol cross condensations can be effective.
Example 4: mixed aldol reactions
The success of these mixed aldol reactions is based on two factors. First, aldehydes are more reactive acceptor electrophiles than ketones, and formaldehyde is more reactive than other aldehydes. Second, aldehydes lacking alpha hydrogens can only act as acceptor reagents, and this halves the number of possible products. Mixed aldols, where both reactants can serve as donor and acceptor, often produce complex mixtures of (homo)dimeric and cross-aldols. For this reason, most mixed aldol reactions do not normally take place unless a reactant has no alpha hydrogens.
The following abbreviated formulas illustrate the possible products in such a case, where the red letters represent the acceptor fraction and the blue letters the donor fraction. If all reactions proceeded at the same rate, equal amounts of all four products would be obtained. It would be difficult to separate and purify the components of such a mixture.
AACH2A +BCH2CHO + NaOH → A–A + B–B + A–B + B–A
The aldol condensation of ketones with aryl aldehydes to give α,β-unsaturated derivatives is calledClaisen SchmidtReaction. This is because adding an enolate to a ketone is not particularly favorable, while adding an enolate to an aldehyde is; that is, the aldehyde is consumed while the ketone serves to provide the enolate moiety for the reaction.
Example 4: Claisen-Schmidt reaction
Another approach is to use LDA in a ketone to quantitatively form the enolate and then react this enolate with the other carbonyl compound. Here, the use of LDA gives control over which compound forms the enolate, although it cannot be used to form aldehyde enolates.
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FAQs
What is aldol reaction in organic chemistry? ›
Aldol Condensation Reaction
Aldol Condensation can be defined as an organic reaction in which enolate ion reacts with a carbonyl compound to form β-hydroxy ketone or β-hydroxy aldehyde, followed by dehydration to give a conjugated enone.
The product formed for aldol condensation is called β-hydroxy aldehyde or β-hydroxy ketone.
How many aldol reaction products may be formed by the reaction of ch3ch2cho? ›Thus, The four possible products are formed when Acetaldehyde and Propanal undergo Aldol condensation.
What is the aldol reaction between two ketones? ›Aldol condensation: An addition reaction between two aldehydes, two ketones, or an aldehyde and a ketone, resulting in a β-hydroxy aldehyde or a β-hydroxy ketone. Subsequent dehydration produces an α,β-unsaturated aldehyde or ketone. The addition step without subsequent dehydration is an aldol reaction.
What are the 2 reactants in the aldol reaction? ›'Aldol' is an abbreviation of aldehyde and alcohol. When the enolate of an aldehyde or a ketone reacts at the α-carbon with the carbonyl of another molecule under basic or acidic conditions to obtain β-hydroxy aldehyde or ketone, this reaction is called Aldol Reaction.
What is the formula for aldol? ›Aldol | C4H8O2 - PubChem.
What are the four steps in the aldol reaction? ›Step 1: The hydroxide ion deprotanates the aldehyde reversibly. Step 2: Enolate ion 1 adds to the unreacted aldehyde. Step 3: Alkoxide ion 2 is protonated by water. Step 4: Aldol 3 is an enolizable aldehyde.
How do you predict the product of aldol condensation? ›Here, the base will abstract the hydrogen to form enolate ion and it will attack the other ketone group to form aldol followed by dehydration to form α,β-unsaturated ketone.
Why is the aldol reaction important? ›Aldol reaction is one of the most important methods for the formation of carbon-carbon bonds. Because of its significance and usefulness, asymmetric versions of this reaction have been realized with different approaches in the past. Over the last decade, the area of organocatalysis has made significant progresses.
What is the maximum number of aldol reaction? ›There are four possible products of aldol condensation between acetaldehyde and propanal.
How many aldols will be formed by ch3cho and ch3ch2cho? ›
Solution : Total four products of aldol condensatio ( excluding steroisomers).
What is the max number of possible major products from a crossed mixed aldol? ›Mixed aldol reactions involve two different carbonyl compounds. Up to four products are possible (two “self-addition” and two “crossed-addition” products).
What is the equation of aldol condensation? ›Aldol condensation of propanone: 2(CH3)2CO dil NaOH (CH3)2C−OH−CH2−CO−CH3H+ Δ(CH3)2C=CH−CO−CH3+H2O.
How many types of aldols are formed in following reaction? ›There are 2 possible enolate ions formed from 2-butanone which attacks on propionaldehyde, to form 4-hydroxy-3-methylhexan-2-one which has 2 chiral carbons, and 5-hydroxyheptan-3-one which has 1 chiral carbon. So there are 6 total possible products.
What is difference between aldol reaction and aldol condensation? ›The reaction of carbonyl compound enolates with aldehydes and ketones to form a β-hydroxy carbonyl compound is the Aldol Reaction, if conditions result in a subsequent dehydration to form the α,β-unsaturated compound, then the reaction is termed the Aldol Condensation (loss of a molecule of water).
What are the reactants of 2 h2 O2? ›For example: hydrogen and oxygen can react to form water as shown in the equation below. 2H2 + O2 → 2H2O (You can disregard the numbers in the equations during this activity.)
What functional group is aldol? ›Aldol: A molecule containing an aldehyde (or ketone) and alcohol functional groups separated by one carbon (i.e., a β-hydroxy aldehyde or β-hydroxy ketone). A contraction of aldehyde alcohol.
How do I know the product of two reactants? ›Reactants are starting materials and are written on the left-hand side of the equation. Products are the end result of the reaction and are written on the right-hand side of the equation.
Why is it called aldol? ›The word aldol is a portmanteau of "aldehyde" and "alcohol". However, it is more generally applied to both beta-hydroxy aldehydes and beta-hydroxy ketones, which are the possible products of the aldol reaction.
What does an aldol addition form? ›An aldol addition is a reaction that occurs between the enolate of an aldehyde or ketone and the alpha-carbon of another aldehyde or ketone to form a beta-hydroxy aldehyde or ketone.
How many steps are in the aldol reaction? ›
Aldol reaction: its chemistry and mechanism. Typically, aldehydes and ketones undergo an aldol reaction. This reaction involves 3 basic steps: Step 1: Electrophilic attack of a base at the alpha-carbon (C αstart subscript, α, end subscript) of the aldehyde or ketone to generate an “enolate” carbanion.
What is the correct order of steps in the aldol mechanism? ›The three steps in this mechanism are: Enolate formation. Nucleophilic attach by the enolate. Protonation.
What is the rate determining step in aldol condensation? ›We now conclude that the rate-limiting step in the base-catalyzed aldol condensation of benzaldehydes with acetophenones, to produce chalcones, is the final loss of hydroxide and formation of the CC bond.
What product results when an aldol is dehydrated? ›The overall reaction is a combination of two major steps, an aldol reaction followed by a dehydration to form the enone.
What is the crude product of aldol condensation? ›Although a β-hydroxyaldehyde (or a β-hydroxyketone) is produced in an aldol condensation, the ultimate product of these reactions (as shown above) is usually the α,β-unsaturated aldehyde (or ketone) and a separate molecule of water.
What happens when aldols readily lose water? ›It readily loses water molecule and undergo aldol condensation.
What is the role of water in aldol condensation? ›Analysis of the reaction mechanism shows that a water molecule eases the condensation process, and may be considered as a catalyst.
What is meant by aldol give an example? ›Aldol structural units are found in many important molecules, whether naturally occurring or synthetic. For example, the aldol reaction has been used in the large-scale production of the commodity chemical pentaerythritol and the synthesis of the heart disease drug Lipitor (atorvastatin, calcium salt).
Which of the following is an example of an aldol reaction? ›C6H5CH2OH.
What are steps for aldol reaction? ›- Step 1: Enolate formation.
- Step 2: Nucleophilic attack by the enolate.
- Step 3: Protonation.
Why is the aldol reaction useful? ›
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.
How many types of aldol are there? ›So there are 6 total possible products.