The Claisen condensation reaction forms new carbon-carbon bonds between two ester 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 enolate formation, nucleophilic addition, 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

• Deprotonation of α carbon by strong base (sodium ethoxide) abstracts an α hydrogen from the ester forming an enolate anion
• Nucleophilic addition of the enolate anion attacks the carbonyl carbon (carbonyl group) of another ester molecule forming a tetrahedral intermediate
• Proton transfer from the conjugate acid of the base protonates the tetrahedral intermediate forming a β-ketoester
• Deprotonation of α carbon in β-ketoester by the strong base deprotonates the α carbon adjacent to the ketone group
• Elimination of alkoxide 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 (carbon-carbon bond formation)
  • 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 α,β-unsaturated ester 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 Claisen condensation 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 cyclic β-ketoester 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 condensation reaction, where two molecules combine to form a larger molecule with the loss of a small molecule (typically water or alcohol)
• Resonance stabilization of the enolate intermediate contributes to the driving force of the reaction
• Keto-enol tautomerism plays a role in the reactivity of the β-ketoester product