CHEM 3220

Aldol Condensation

Harris/ Dandekar

Aldol Condensation
Chapter 37 37.1: Synthesis of dibenzalacetone
O O O

+ acetone

NaOH 95% EtOH (solvent) dibenzalacetone (E,E isomer)

benzaldehyde

Theory:
Reactivity: o Acidity of alpha hydrogen atoms: pKa of hydrogen atoms to >C=O groups: ~20 SO:
o

In presence of base, proton abstraction affords enolate ions: Resonance stabilized Excellent Nucleophiles Nucleophilic addition to the carbonyl group gives the addition product: aldol adduct Spontaneous dehydration of the adduct: aldol condensation product Why is dehydration so facile? o Conjugated enal or enone E isomers tend to predominate

Different types of aldol condensations: o Normal Same aldehyde (or ketone) as substrate and nucleophile o Crossed Two different aldehydes (or ketones) Up to 4 products obtained under these conditions Synthetically useful when one reactant lacks - hydrogens
o

Claisen-Schmidt (mixed aldol) Condensation reaction between an aldehyde and a ketone The aldehyde carbonyl is moe reactive than that of the ketone, and therefore, reacts rapidly with the anion of the ketone to give a beta-hydroxyketone, which easily undergoes base-catalyzed dehydration Good to use NaOH so that the ketones dont significantly self-condense

CHEM 3220

Aldol Condensation

Harris/ Dandekar

Forms conjugation between carbonyl group, alkene, and benzene ring

Reaction Mechanism:
:O :
H O

:O :
:

:O :

OH

: H 2O

:O :
:

enolate ion

OH

aldol adduct [- H 2O]

O

OH dibenzalacetone (E,E isomer)

repeat all steps at the other - position

aldol condensation product (E isomer)

Note Stoichiometry: o Need 2 moles of benzaldehyde : 1 mole acetone By-product: o Self-condensation product(s): It is possible for the enolate ion (from acetone) to add to the carbonyl group of a second acetone molecule, ultimately leading to the corresponding condensation product(s).
:O: : + :O: :O:
OH

[- H2O] : O :

:O:

CHEM 3220

Aldol Condensation

Harris/ Dandekar

It is often possible to minimize the formation of this type of by-product by careful experimental design By adding acetone (diluted with solvent) dropwise to a mixture of benzaldehyde and base, the statistical possibility of selfcondensation is minimized.

Experiment:
Aldol Condensation: Exp 37.1: Synthesis of Dibenzalacetone Follow the procedure given on pp. 485-486. Stoichiometry is critical: o Insufficient quantity of benzaldehyde (i.e., less than 2 mol equivalents) will decrease yield Note the role of the solvent(s): o Protic solvent: water (from aq NaOH) and/or ethanol is involved in the mechanism o Quantity of ethanol is critical: Enough to allow the reactants as well as the principal intermediate ( benzalacetone ) to be soluble, but not enough to dissolve the product SO: The product precipitates out o Drives the reaction to completion During work-up: o The base residue is removed by thorough washing with water Why not simply neutralize with acid ? Can the product react with aqueous acid?

You dont need to: o weigh your product and o determine the percent yield. Do record the melting point of the product.

Pre-Lab Assignment

LabBook: Q 3- 4 pp. 488

Reading Assignment

LabBook: Chapter Ch 37 Also Read: Aldol condensation and related reactions from an organic textbook (e.g., Jones/Fleming or Solomons/Fryhle)

Post-Lab Assignment

Draw the structures of the (E,Z) and (Z,Z) isomers of dibenzal.

3

CHEM 3220

Aldol Condensation

Harris/ Dandekar

Do you expect dibenzal to have a characteristic UV absorption? Explain.