15.23
Ketones with Nonenolizable Aromatic Aldehydes: Claisen–Schmidt Condensation
Benzaldehyde, like formaldehyde, lacks an α hydrogen and cannot enolize to form an enolate. Hence, the reaction of benzaldehyde with a ketone in the p…
Recall that the self-condensation of ketones in basic conditions is not favored.
Accordingly, in an aqueous base and external heating, the ketone reacts with benzaldehyde that lacks an α hydrogen to form a single unsaturated carbonyl product. This reaction is called Claisen–Schmidt condensation.
As for the mechanism, the ketone enolate attacks the benzaldehyde to exclusively form the unsaturated carbonyl product, instead of an aldol. This is attributed to the extended conjugation that stabilizes the product.
Between the cis and trans stereoisomers of the product, the trans isomer is obtained in high yield because it has fewer steric interactions.
Aromatic ketones undergo a similar reaction with benzaldehyde to generate a trans isomer as the major product.
Claisen–Schmidt condensation can also be performed in acidic conditions.
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Q1: Why does Claisen–Schmidt condensation produce a single product instead of self-condensation?
Benzaldehyde lacks an α hydrogen and cannot form an enolate, preventing self-condensation of the ketone. In aqueous base, the ketone enolate attacks benzaldehyde exclusively, forming one unsaturated carbonyl product. Self-condensation of ketones is thermodynamically unfavorable under these basic conditions, so only the crossed product forms.
Q2: What is the mechanism of Claisen–Schmidt condensation?
Base deprotonates the α carbon of the ketone to form a ketone enolate. The enolate then attacks the carbonyl carbon of benzaldehyde, forming an unsaturated carbonyl product rather than an aldol intermediate. Extended conjugation in the unsaturated product stabilizes the molecule, driving the reaction toward this single final product.
Q3: Why is the trans isomer the major product in Claisen–Schmidt condensation?
The trans stereoisomer has fewer steric interactions between substituents compared to the cis isomer. This reduced steric strain makes the trans configuration more stable and thermodynamically favored. Consequently, trans products are obtained in high yield for both simple ketones and aromatic ketones reacting with benzaldehyde.
Q4: How does extended conjugation stabilize the Claisen–Schmidt product?
The unsaturated carbonyl product contains an extended conjugated system that delocalizes electrons across the π bonds and carbonyl group. This delocalization lowers the energy of the product, making it more stable than the aldol intermediate. The conjugation explains why the reaction favors the unsaturated product over other possible intermediates.
Q5: Can Claisen–Schmidt condensation be performed under acidic conditions?
Yes, Claisen–Schmidt condensation can be performed in acidic conditions as well as basic conditions. The reaction mechanism adapts to the acidic environment while still producing the unsaturated carbonyl product. Both aromatic and aliphatic ketones undergo this condensation with benzaldehyde under acidic catalysis.
Q6: What role does benzaldehyde's lack of α hydrogens play in this reaction?
Benzaldehyde cannot enolize because it lacks an α hydrogen, making it unable to form an enolate nucleophile. This property ensures benzaldehyde acts exclusively as an electrophile, accepting the attack from the ketone enolate. The absence of competing enolate formation from benzaldehyde guarantees formation of a single crossed product.
Q7: Do aromatic ketones undergo Claisen–Schmidt condensation differently than aliphatic ketones?
Aromatic ketones undergo similar Claisen–Schmidt condensation with benzaldehyde in basic conditions, generating the trans isomer as the major product. The reaction mechanism and product selectivity remain consistent regardless of whether the ketone is aromatic or aliphatic, with extended conjugation stabilizing the unsaturated carbonyl product.