Claisen-Schmidt Condensation

Claisen-Schmidt Condensation forms α,β-unsaturated carbonyl compounds by reacting aromatic aldehydes with ketones in base.

• The Claisen–Schmidt condensation is a base-catalyzed aldol condensation between an aromatic aldehyde and a ketone (or sometimes another aldehyde) with α-hydrogens, typically resulting in an α,β-unsaturated carbonyl compound.

General Reaction:

Aromatic aldehyde  +  Aliphatic ketone —(Base/heat) →  α,β-unsaturated ketone  +  H₂O

Example of Claisen-Schmidt Condensation:

Benzaldehyde + Acetophenone → Chalcone

Ph–CHO  +  Ph–COCH₃  →  Ph–CH=CH–CO–Ph  +  H₂O

Reaction Conditions

• Base catalyst: Typically, NaOH or KOH
• Solvent: Ethanol or methanol
• Heat: Often required to drive the elimination step

Mechanism (Step-by-Step)

Let’s take benzaldehyde and acetophenone as an example:

• Step 1: Enolate Formation

  • The base abstracts an α-proton from acetophenone, forming an enolate ion.
    • Ph–COCH₃  +  OH⁻  →  Ph–C⁻=CH₂ (enolate)  +  H₂O

• Step 2: Nucleophilic Addition to Aldehyde

  • The enolate ion attacks the carbonyl carbon of benzaldehyde.
  • Forms a β-hydroxy ketone intermediate (aldol addition product).
    • Ph–C⁻=CH₂  +  Ph–CHO  →  Ph–CH(OH)–CH₂–CO–Ph

• Step 3: Aldol Condensation (Elimination)

  • Under heat, the β-hydroxy ketone eliminates water to form an α,β-unsaturated ketone (chalcone).
    • Ph–CH(OH)–CH₂–CO–Ph  →  Ph–CH=CH–CO–Ph  +  H₂O
  • This elimination proceeds via an E1cb mechanism (conjugate base elimination), where:
  • The base removes a proton from the β-carbon.
  • The resulting enolate eliminates the hydroxide (or water) from the α-carbon.

Features of Claisen–Schmidt Condensation

• Crossed aldol: between two different carbonyl compounds (one aldehyde, one ketone).
• One component (aldehyde) usually lacks α-hydrogens to prevent self-condensation.
• Forms conjugated systems: the α,β-unsaturated carbonyl is stabilized by resonance.
• Used in synthesis of:
  • Chalcones
  • Flavonoids
  • Pharmaceuticals
  • Natural products

Key Considerations of Claisen-Schmidt Condensation

• Selectivity: Controlled by using one reactant without α-hydrogens.
• Base choice: Strong enough to form enolate but not so strong to cause side reactions.
• Solvent: Must solubilize both organic and inorganic components.
• Temperature: Higher temperatures favor condensation (dehydration step).

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