1 Department of Organic Chemistry E.T.

27 - Hipólito Yrigoyen

Practical Work of Organic Chemistry II

Practical Work No. 1: Aldol Condensation

Introduction:
Aldol condensation is one of the so-called 'powerful reactions' in organic chemistry.
well allows the synthesis of compounds with a new C-C bond. The products of this reaction are
alpha-beta unsaturated compounds, which are commonly used in organic synthesis, although also
they have other commercial applications.
Ladibenzalacetone is the product of the aldol condensation between acetone and benzaldehyde.
It is commercially used as an active ingredient in sunscreens due to its chains.
of conjugated double bonds that are capable of absorbing the UV radiation emitted by the Sun:

Theoretical Fundamentals:
The condensations correspond to a set of chemical reactions in which two
molecules join by eliminating a small molecule (usually a water molecule or some
small alcohol); in aldol condensations, a molecule of aldehyde or ketone that presents
alpha hydrogens (hydrogen on the carbon adjacent to the carbonyl carbon) bond with another aldehyde or
ketone, forming an intermediate known as aldol, which is subsequently dehydrated
forming the product of the condensation.
The carbonyl group is an electron attractor due to its high electronegativity.
of the oxygen atom, this causes that by inductive effect, the C-H bonds of
the carbons sp3in the alpha position to the carbonyl are polarized and therefore these
hydrogens present certain acidity:

The pKa values of these hydrogens for aldehydes and ketones range from
16 and 20, much more acidic than the hydrogens of aliphatic hydrocarbons (whose pKa value is
greater than 60 for alkanes.

These hydrogens can be captured with suitable bases, resulting in a carbanion that
stabilizes by resonance, forming an enolate anion (the more stable the conjugate base is
formed, the more acidic the hydrogens of the compound will be):
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This enolate is an excellent nucleophile that is capable of attacking electrophiles, such as a carbon.
carbonyl of a non-enolized aldehyde or ketone, leading to aldol condensation.
Enolates are very good nucleophiles, and once formed they attack any electrophile in the system.
the equilibrium of enolization shifted to the right, forming more enolate available for the reaction. This
explain that the reaction is slow, and that time is needed for it to evolve and for the result to be obtained
a reasonable performance.

In general, this reaction yields better results when trying to condense two compounds.
carbonyls, one with alpha hydrogens and the other without alpha hydrogens, since in this way only one of
these can be enolized. Thus, a cross-condensation compound can be formed (the one that is
generates from the reaction between the carbonyl compound with alpha hydrogens and the one that does not have them), and
the autocondensation product (the one generated by the reaction between two compound molecules
carbonyl, one enolized and the other not enolized.
Autocondensation can be hindered by preparing a mixture of the base and the compound.
carbonyl without alpha hydrogens, and adding to this the enolizable carbonyl compound. It is also
it is reasonable to use the latter as the limiting reagent.

The final dehydration allows for the shift of equilibria. An extraction can also be carried out.
from the aldol of the reaction medium to favor the reaction.

We will study the mechanism of this reaction for the condensation of acetone with benzaldehyde.
catalyzed by sodium hydroxide. Since benzaldehyde is an aldehyde without hydrogens in the
alpha carbon, it cannot be enolized, and therefore only acetone will do so:

Synthesis of Dibenzalacetone
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Reaction mechanism

Formation of the Enolate

This enolate attacks the carbonyl carbon of benzaldehyde, binding and forming the intermediate
known as aldol:

Finally, the aldol is dehydrated.

forming the compound of
aldol condensation.

Since acetone still has an enolizable hydrogen, it can react with another molecule of acetone.
finally forming dibenzalacetone.
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When preparing the reaction mixture, certain experimental considerations must be taken into account.

1.- Do not initially mix sodium hydroxide with acetone as it can self-condense.

2.- Use an excess of benzaldehyde since the excess will not enolize, so that it
condense with the two available alpha hydrogens of acetone to shift the equilibrium of the
reaction to the right.
3.- The reaction can be completed by adding an acid that neutralizes the sodium hydroxide in it.
The form will no longer undergo enolization, and aldol condensation will not be feasible.
4.- Benzaldehyde is not miscible with aqueous solutions, so it is necessary to add some
organic solvent that favors its mixing (such as ethanol).

Experimental Part:
Materials: Erlenmeyer flasks, graduated pipettes, beakers, vacuum filtration equipment,
Filter Paper, Burner, Cans for Double Boiler, Glass Rod, Lighter or match, Ice
Fisher-Jones apparatus or Thiel tubes, thermometers.
Reactivos:Acetona, Benzaldheído, Solución de Hidróxido de Sodio 2 N, Ácido Acético Glacial, Etanol.

Procedure: In a 125 mL Erlenmeyer flask, place 7 mmol of acetone and 20 mmol of

benzaldehyde. Add to this mixture 10 mL of 95% ethanol and 7.5 mL of aqueous solution of
Sodium hydroxide 2 N. Let react, shaking periodically and scraping the walls of
container with a rod to induce crystallization. This procedure can take between 15 to 20
minutes gently heating in a water bath. Let cool, and place in an ice bath, then
filter by vacuum and wash with successive portions of cold 95% ethanol, 4% acetic acid in ethanol
95% cold ethanol and finally 95% cold ethanol.
Recrystallize in 95% ethanol (hot on a heating plate) and calculate the yield of the
reaction. Measure the melting point of the obtained product.

Note: Look up in tables the data for the corresponding molar masses and densities of benzaldehyde.
of acetone to perform the conversion of moles to mL or g depending on whether these reactants are solids or liquids.
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Thin Layer Chromatography (TLC)

Perform chromatography comparing the raw material and the obtained product.
Sample solvent: Acetone or Ethyl acetate.
Mobile phase: Hexane - Ethyl acetate 5:1
Revealer: UV Light.

Characterization reactions

Double bonds: Cold and diluted potassium permanganate.

Carbonyl group: Dinitrophenylhydrazine.
Aldehydes: Tollens test.
Methyl ketones: Lieben test - Haloform

Chalcones are substances used in the synthesis of heterocyclic compounds. How do they
do they obtain?
Alpha, beta-unsaturated ketones are biogenetic precursors of flavonoids in higher plants. They are
known as chalcones and consist of open-chain flavonoids in which two groups
Phenyls are linked by an enone bridge. They are commonly synthesized via reactions of
Claisen-Schmidt condensation between acetophenone and benzaldehyde, under catalytic conditions
acidic or basic homogeneous in organic solvents.
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I.R. Spectra
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Questionnaire:
Describe with balanced chemical equations the synthesis carried out.
limiting factor of the reaction? Explain why it is chosen.

3.- Propose the mechanism for the reaction of one mole of acetone with two moles of benzaldehyde.
catalyzed by sodium hydroxide.
4.- What would happen if a student leaves the acetone - hydroxide mixture for too long without adding?
the aldehyde? Formulate the reaction that would take place.

5.- What advantage does using aromatic aldehydes have over aliphatic ones in aldol condensation?
6.- Why is it necessary to warm up gently for a while?
7.- What is the purpose of scraping the walls of the Erlenmeyer with the rod? What is achieved with this?
8.- Explain the end of the washes to the obtained precipitate.
9.- Calculate the mass of dibenzalacetone that would be obtained if 5 mL of acetone is mixed with 10
mL of benzaldehyde, with the appropriate amount of basic catalyst.
10.- What volume of acetone and benzaldehyde is needed to obtain 10 g of dibenzalacetone?
with a 67% efficiency?
11.- Explain why you should add benzaldehyde first and then acetone to the mixture.
reaction.
12.- Explain why only one product is obtained and not a mixture of products in this practice.

13.- Indicate why the aldol produced easily undergoes crotonization.

14.- Why should the solution not be alkaline during recrystallization?

Bibliography:

Practical Work Guide for Organic Chemistry II 2nd Semester 2014 - FCEN, UBA.
Illustrations made by Facundo Daniel Agostini.