23.8 Mixed Claisen Condensations
2 min read•may 7, 2024
Mixed Claisen condensations bring together two different to create new carbon-carbon bonds. This reaction pairs an or as the with a or as the , forming β-diketones under carefully controlled conditions.
The process hinges on formation from the ketone, which then attacks the ester's carbonyl. Strong bases, , and specific solvents and temperatures are crucial. The resulting β-diketones feature two carbonyls separated by a group.
Mixed Claisen Condensations
Components of mixed Claisen condensation
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- Two different carbonyl compounds react together
- Ester (ethyl acetate) or formate serves as the electrophilic carbonyl acceptor
- Ketone (acetone) or aldehyde acts as the nucleophilic carbonyl donor providing the enolate
- Strong base deprotonates the α-carbon of the ketone to form the enolate nucleophile
- Common bases include or
- Anhydrous conditions prevent hydrolysis of the ester or the product
- Moisture can react with the ester or product leading to undesired side reactions
- Polar aprotic solvent facilitates the reaction by stabilizing charged intermediates
- Examples include (THF) or
- Typical reaction temperature range from 0°C to room temperature (25°C)
- Low temperatures favor formation of the and minimize side reactions
Products of ester-ketone condensations
- The enolate of the ketone acts as a nucleophile attacking the electrophilic carbonyl carbon of the ester
- The group of the ester is eliminated forming a new carbon-carbon bond
- Bond forms between the α-carbon of the ketone and the carbonyl carbon of the ester
- The resulting intermediate undergoes to form the product
- The of the ketone is more acidic than the α-hydrogen of the ester
- Favors formation of the ketone enolate and the β-diketone product
- The β-diketone product has two carbonyl groups separated by a methylene () group
- Reaction between and ethyl acetate yields
- Two carbonyl groups flank the central in the product
Effective electrophilic acceptor esters
- has a highly electrophilic carbonyl carbon
- Electron-withdrawing effect of the aromatic ring
- Resonance effect of the benzene ring delocalizes electrons away from the carbonyl group
- Increased electrophilicity makes it more susceptible to nucleophilic attack
- has a highly electrophilic carbonyl carbon
- Absence of an α-carbon prevents competing enolate formation
- Carbonyl group is more electrophilic compared to other esters
- Effective acceptor in mixed Claisen condensations
- The group is a good
- Facilitates the elimination step
- Enables efficient formation of the β-diketone product
Reaction Mechanism and Key Concepts
- is a type of
- It is a involving nucleophilic addition followed by elimination
- The enolate acts as the nucleophile, while the ester carbonyl serves as the electrophile
- The alkoxide group of the ester functions as the during the reaction
Key Terms to Review (31)
1-phenylbutane-1,3-dione: 1-phenylbutane-1,3-dione is a diketone compound with a phenyl group attached to one of the carbonyl carbons and two ketone groups separated by two methylene groups. This compound is relevant in the context of mixed Claisen condensations, a type of carbon-carbon bond forming reaction.
1,3-diketone: A 1,3-diketone is a type of organic compound that contains two carbonyl (C=O) groups separated by a single carbon atom. These compounds exhibit unique chemical properties that make them important in various organic chemistry reactions and applications.
Acetophenone: Acetophenone is an aromatic ketone compound with the chemical formula C6H5COCH3. It is a colorless liquid with a characteristic floral odor and is widely used in the production of various organic compounds and as a fragrance in personal care products.
Aldehyde: An aldehyde is a class of organic compounds containing a carbonyl group (C=O) where the carbon atom is bonded to one hydrogen atom and one alkyl or aryl group. Aldehydes are important functional groups in organic chemistry and are involved in various reactions and synthesis pathways.
Alkoxide: An alkoxide is a functional group consisting of an alkyl group (R-) bonded to an oxygen atom (O-). Alkoxides are important intermediates in many organic chemistry reactions, including Grignard reactions, elimination reactions, and carbonyl condensation reactions.
Anhydrous Conditions: Anhydrous conditions refer to the absence of water or moisture in a chemical reaction or process. This term is particularly important in the context of certain organic chemistry reactions where the presence of water can interfere with the desired outcome.
Base-Catalyzed Reaction: A base-catalyzed reaction is a type of chemical reaction in which a basic substance (a proton acceptor) accelerates the rate of the reaction by providing an alternative pathway with a lower activation energy. This term is particularly relevant in the context of 23.8 Mixed Claisen Condensations, where a base is used to facilitate the formation of new carbon-carbon bonds.
Carbonyl Compounds: Carbonyl compounds are a class of organic compounds that contain a carbon-oxygen double bond (C=O), known as the carbonyl group. This functional group is found in a variety of important molecules, including aldehydes, ketones, carboxylic acids, esters, and amides, which are all integral to many organic chemistry topics and reactions.
Condensation Reaction: A condensation reaction is a type of chemical reaction where two molecules combine to form a single molecule, often with the elimination of a small molecule such as water or ammonia. This process is fundamental in the formation of many organic compounds, including polymers, peptides, and various condensation products.
Diethyl Ether: Diethyl ether is a colorless, highly volatile, and flammable liquid ether that has been widely used as an anesthetic, as a solvent, and in various organic chemistry reactions. It is an important compound that is closely tied to several key topics in organic chemistry.
Electrophile: An electrophile is a species that is attracted to electron-rich regions and seeks to form new bonds by accepting electron density. Electrophiles play a crucial role in many organic reactions, including polar reactions, electrophilic aromatic substitution, and nucleophilic acyl substitution, among others.
Enolate: An enolate is a negatively charged oxygen-containing species that arises from the removal of a proton from the α-carbon of a carbonyl compound. Enolates are important reactive intermediates in various organic reactions, including aldol condensations, Claisen condensations, and α-substitution reactions.
Ester: An ester is a chemical compound formed by the reaction between an organic acid and an alcohol, resulting in the replacement of the hydrogen atom of the acid by an alkyl or aryl group. Esters are widely encountered in various topics in organic chemistry, including functional groups, oxidation-reduction reactions, alcohol formation, and spectroscopy.
Ethoxide: Ethoxide is a functional group consisting of an ethyl group (CH3CH2-) bonded to an oxygen atom. It is an important intermediate in various organic reactions, particularly in the context of E2 reactions, ester chemistry, and Claisen condensations.
Ethyl Benzoate: Ethyl benzoate is an ester compound formed by the reaction between benzoic acid and ethanol. It is a colorless, aromatic liquid with a sweet, fruity odor, commonly used as a flavoring agent and in the synthesis of other organic compounds.
Ethyl Formate: Ethyl formate is an organic compound with the chemical formula HCOOC₂H₅. It is a colorless, volatile liquid ester that is commonly used as a flavoring agent and solvent in various industries.
Formate: Formate is the conjugate base of formic acid, the simplest carboxylic acid. It is a key intermediate in various metabolic pathways and chemical reactions, including the Claisen condensation.
Ketone: A ketone is a functional group in organic chemistry that consists of a carbonyl group (a carbon-oxygen double bond) bonded to two alkyl or aryl groups. Ketones are widely encountered in various organic chemistry topics, including the hydration of alkynes, oxidative cleavage of alkynes, organic synthesis, oxidation and reduction reactions, and the chemistry of aldehydes and ketones.
Kinetic Enolate: A kinetic enolate is a reactive intermediate formed in organic chemistry reactions involving carbonyl compounds. It is a negatively charged oxygen-containing species that is generated under kinetic conditions, typically through the use of a strong base, and can undergo further transformations to form new carbon-carbon bonds.
Leaving group: A leaving group in organic chemistry is an atom or group that detaches from the parent molecule during a nucleophilic substitution (SN2) reaction, forming a lone pair or negative ion. The ease with which a leaving group departs affects the rate and success of the reaction.
Leaving Group: A leaving group is a functional group or atom that is displaced or removed from a molecule during a chemical reaction. It is a key component in many organic reactions, particularly substitution and elimination reactions, as it facilitates the formation of a new bond or the creation of a new product.
Methylene: Methylene refers to a chemical group with the formula -CH2-, which consists of a carbon atom bonded to two hydrogen atoms. This group is crucial in organic chemistry as it serves as a building block for larger molecules and can influence the structure and reactivity of compounds, particularly those with sp² hybridization, such as ethylene. Understanding methylene's role is essential in areas like NMR spectroscopy and reactions involving carbonyl compounds.
Mixed Claisen Condensation: A Mixed Claisen Condensation is a type of organic reaction in which two different carbonyl compounds, typically an ester and a ketone or aldehyde, undergo a condensation reaction to form a new β-keto ester product. This reaction is a variation of the Claisen condensation, which involves the reaction of two ester compounds.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
Proton Transfer: Proton transfer is a fundamental chemical process in which a proton (H+) is donated from one species to another. This process is central to understanding acid-base reactions, reaction mechanisms, and the behavior of biological systems involving acids and bases.
Sodium Ethoxide: Sodium ethoxide is an alkoxide compound with the chemical formula C₂H₅ONa. It is a strong nucleophile and base used in various organic reactions, including the preparation of alkenes, the Wittig reaction, and Claisen condensations.
Sodium Hydride: Sodium hydride (NaH) is a chemical compound consisting of a sodium cation (Na+) and a hydride anion (H-). It is a strong reducing agent and a powerful nucleophile, making it a versatile reagent in organic chemistry.
Tetrahydrofuran: Tetrahydrofuran (THF) is a cyclic ether compound with the chemical formula (CH2)4O. It is a colorless, volatile, and flammable liquid that is widely used as a solvent and as a building block in organic synthesis.
α-Hydrogen: α-Hydrogen refers to the hydrogen atom that is directly bonded to the carbon atom adjacent to a carbonyl group (a carbon-oxygen double bond). This term is particularly relevant in the context of various organic chemistry topics, including the names and properties of ethers, the oxidation of aldehydes and ketones, carbonyl condensations, and mixed Claisen condensations.
β Diketone: A β-diketone is an organic compound containing two ketone groups separated by a carbon atom, which is the beta (β) position relative to each ketone group. These molecules are characterized by the presence of hydrogen atoms on the carbon between the two carbonyl (C=O) groups, making them acidic and prone to enolate ion formation.
β-diketone: A β-diketone is a type of organic compound that contains two carbonyl (C=O) groups separated by a single carbon atom. This structural feature allows for unique reactivity and tautomeric behavior, making β-diketones an important class of compounds in organic chemistry, particularly in the context of the Claisen condensation reaction and mixed Claisen condensations.