23.7 The Claisen Condensation Reaction
3 min read•may 7, 2024
The forms new carbon-carbon bonds between two molecules. It's a powerful tool for creating larger, more complex organic compounds from simpler starting materials.
This reaction showcases key organic chemistry concepts like formation, , and elimination. Understanding its mechanism and products is crucial for grasping how molecules can be built up step-by-step.
Claisen Condensation Reaction
Mechanism of Claisen condensation
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- of by strong base () abstracts an α hydrogen from the ester forming an enolate anion
- Nucleophilic addition of the enolate anion attacks the carbonyl carbon () of another ester molecule forming a
- Proton transfer from the conjugate acid of the base protonates the tetrahedral intermediate forming a
- Deprotonation of α carbon in β-ketoester by the strong base deprotonates the α carbon adjacent to the ketone group
- Elimination of from the resulting enolate anion expels an alkoxide group and forms a carbon-carbon double bond
- Protonation of alkoxide by the conjugate acid of the base regenerates the alcohol
Claisen vs aldol condensation
- Similarities
- Both form a new carbon-carbon bond ()
- Both create an enolate intermediate
- Both result in the formation of a β-hydroxy carbonyl compound (aldol) or β-ketoester (Claisen) before dehydration
- Differences
- Reactants: Claisen uses two ester molecules while aldol uses two aldehyde or ketone molecules
- Base strength: Claisen requires a strong base (sodium ethoxide) while aldol can use a weaker base (sodium hydroxide)
- Products: Claisen forms a β-ketoester which can undergo further deprotonation and elimination to form a while aldol forms a β-hydroxy aldehyde or ketone which can dehydrate to form an α,β-unsaturated aldehyde or ketone
- Reaction conditions: Claisen typically requires heating and anhydrous conditions while aldol can often be carried out at room temperature and in the presence of water
Predicting Claisen condensation products
- Esters with two or more α hydrogens will undergo to form a β-ketoester which can further react via deprotonation and elimination to form an α,β-unsaturated ester
- Esters with only one α hydrogen will form a β-ketoester but cannot undergo further deprotonation and elimination stopping the reaction at the β-ketoester stage
- Esters with no α hydrogens cannot undergo Claisen condensation due to the lack of acidic α hydrogens
- Cyclic esters can undergo Claisen condensation if they possess α hydrogens resulting in a product which may undergo further reactions depending on the number of remaining α hydrogens
- Unsymmetrical esters will preferentially deprotonate the more acidic α carbon with the resulting enolate acting as the nucleophile in the reaction
Additional Concepts in Claisen Condensation
- The Claisen condensation is a type of , where two molecules combine to form a larger molecule with the loss of a small molecule (typically water or alcohol)
- of the enolate intermediate contributes to the driving force of the reaction
- plays a role in the reactivity of the β-ketoester product
Key Terms to Review (31)
Aldaric acid: Aldaric acid is a type of dicarboxylic acid obtained by oxidizing both the aldehyde and primary alcohol groups of an aldose to carboxylic acids. It represents the fully oxidized form of a monosaccharide where all potential reactive sites have been converted to carboxyl groups.
Aldol Condensation: Aldol condensation is a type of organic reaction where an aldehyde or ketone undergoes a nucleophilic addition reaction with another aldehyde or ketone, followed by a dehydration step to form an α,β-unsaturated carbonyl compound known as an enone.
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.
Aprotic Solvent: An aprotic solvent is a type of organic solvent that does not contain an active hydrogen atom and does not participate in hydrogen bonding. These solvents are commonly used in various organic chemistry reactions, including the E1 and E1cB reactions, the reduction of carbonyl compounds, the Wittig reaction, and the Claisen condensation reaction.
Base-Catalyzed: Base-catalyzed refers to a chemical reaction where a basic compound, such as a hydroxide ion or an amine, acts as a catalyst to increase the rate of the reaction. This term is particularly relevant in the context of organic chemistry, specifically in the reactions of epoxides and the Claisen condensation reaction.
Carbon-Carbon Bond Formation: Carbon-carbon bond formation is a fundamental process in organic chemistry that involves the creation of new carbon-carbon bonds, which are the backbone of organic molecules. This term is particularly relevant in the context of various reactions and mechanisms that facilitate the construction of more complex organic structures from simpler starting materials.
Carbonyl group: A carbonyl group is a functional group characterized by a carbon atom double-bonded to an oxygen atom, represented as C=O. This group is pivotal in organic chemistry as it forms the backbone of various important classes of compounds, influencing their chemical properties and reactivity.
Claisen Condensation: The Claisen condensation is a carbon-carbon bond-forming reaction that occurs between the α-carbon of one carbonyl compound and the carbonyl carbon of another carbonyl compound, resulting in the formation of a β-keto ester or β-diketone. This reaction is a key step in many organic synthesis pathways and is closely related to the concepts of functional groups, enolate ion formation, and biological carbonyl condensation reactions.
Claisen condensation reaction: A Claisen condensation reaction is an organic chemical reaction where two esters or one ester and another carbonyl compound react in the presence of a strong base, leading to the formation of a β-keto ester or a β-diketone. It's a key method for forming carbon-carbon bonds in organic synthesis.
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.
Cyclic β-Ketoester: A cyclic β-ketoester is a type of organic compound that contains a cyclic structure with a carbonyl group (ketone) and an ester group at the β-position. These compounds are important intermediates in various organic reactions, particularly the Claisen condensation reaction.
Deprotonation: Deprotonation is the process of removing a proton (H+) from a molecule or ion, resulting in the formation of a negatively charged species. This chemical reaction is central to various organic chemistry topics, as it allows for the generation of reactive intermediates and the manipulation of molecular structures.
Dieckmann Cyclization: The Dieckmann cyclization is an intramolecular Claisen condensation reaction that forms cyclic β-keto esters from linear diester precursors. It is a powerful synthetic tool for the construction of carbocyclic and heterocyclic compounds.
Dieckmann cyclization reaction: The Dieckmann cyclization reaction is an intramolecular chemical process in Organic Chemistry where a dicarboxylic acid ester undergoes condensation to form a cyclic β-keto ester under the influence of a base. It serves as a specific example of intramolecular Claisen condensation, crucial for synthesizing five- or six-membered rings.
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.
Keto-Enol Tautomerism: Keto-enol tautomerism is the reversible chemical equilibrium between a keto (carbonyl) form and an enol form of a compound. This process is particularly relevant in the context of carbonyl chemistry, as it affects the reactivity and properties of these compounds.
LDA (Lithium Diisopropylamide): LDA, or lithium diisopropylamide, is a powerful organometallic base commonly used in organic chemistry for the deprotonation of alpha-hydrogen atoms, generating highly reactive enolate ions. This key term is closely related to various topics in the study of carbonyl chemistry, including enolate ion formation, reactivity, and subsequent reactions.
Nucleophilic Addition: Nucleophilic addition is a fundamental organic reaction in which a nucleophile, a species that donates electrons, adds to an electrophilic carbon center, typically a carbonyl carbon, to form a new product. This reaction is central to understanding many important topics in organic chemistry, including functional groups, polar reactions, carbocation stability, reaction stereochemistry, and the chemistry of aldehydes, ketones, alcohols, and other carbonyl-containing compounds.
Nucleophilic addition reaction: A nucleophilic addition reaction is a chemical process where a nucleophile forms a bond with an electrophilic carbon atom of a compound, typically found in aldehydes and ketones. This reaction results in the conversion of the carbonyl group into a more complex, often larger, molecule.
Polar aprotic solvents: Polar aprotic solvents are solvents that have a net dipole moment but do not possess hydrogen atoms capable of forming hydrogen bonds. They are used in organic reactions to dissolve electrolytes and facilitate reactions without participating in them.
Rainer Ludwig Claisen: Rainer Ludwig Claisen was a German chemist who made significant contributions to the field of organic chemistry, particularly in the development of the Claisen condensation reaction, an important carbon-carbon bond forming reaction.
Resonance Stabilization: Resonance stabilization is a phenomenon where the delocalization of electrons in a molecule or ion leads to a more stable configuration compared to a single Lewis structure. This concept is crucial in understanding the behavior and properties of various organic compounds, including their acidity, basicity, reactivity, and stability.
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.
Tetrahedral Intermediate: A tetrahedral intermediate is a key reaction step that occurs in many organic chemistry reactions, where a trigonal planar carbonyl carbon temporarily becomes a tetrahedral carbon with four bonded atoms. This transient intermediate is crucial for understanding the mechanisms of various nucleophilic addition and substitution reactions.
α Carbon: The α carbon is the carbon atom directly bonded to the carbonyl carbon in organic compounds. It plays a crucial role in various chemical reactions, including the Claisen condensation reaction, due to its unique reactivity and position within the molecule.
α,β-unsaturated ester: An α,β-unsaturated ester is a type of organic compound that features a carbonyl group (ester) directly attached to a carbon-carbon double bond. This structural arrangement creates a system of conjugated double bonds, which gives rise to unique reactivity and properties.
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.
β-Keto ester: A β-keto ester is an organic compound containing a ketone functional group (carbonyl) and an ester group, where the carbonyl carbon is positioned two carbons away from the ester oxygen. This structure makes the hydrogen atoms on the carbon between the carbonyl and ester groups (alpha hydrogens) particularly acidic, facilitating their removal and formation of enolate ions.
β-keto ester: A β-keto ester is a type of organic compound that contains a ketone group (C=O) at the β-carbon position relative to an ester functional group. These compounds are important intermediates in various organic reactions, particularly in the context of enolate ion reactivity, the Claisen condensation reaction, and certain biological carbonyl condensation reactions.
β-ketoester: A β-ketoester is a type of organic compound that contains both a ketone group and an ester group, with the ketone group located at the β-carbon position relative to the ester group. This structural feature allows β-ketoesters to participate in a variety of important organic reactions, including the Claisen condensation, Dieckmann cyclization, and Michael addition.