CM134L-A7

Experiment No. 4
Group No. 4
MAPUA UNIVERSITY
ROYAL JOURNAL OF ORGANIC CHEMISTRY II

SYNTHESIS VIA ALDOLA AND MIXED ALDOL CONDENSATION

Dr. Kathlia De Catsro-Cruz1, Gerald C. Domingo2, Sean Irvine San Luis3
1 Professor, School of Chemical, Biological and Material Engineering and Sciences, Mapua University
2 Student, CM134L/A7, School of Chemical, Biological and Material Engineering and Sciences, Mapua

ABSTRACT

The synthesis of dibenzalacetone proceeds by the reaction of acetone and benzaldehyde using
sodium hydroxide as base. The process involves deprotonation of the α-hydrogen forming an
enolate anion, nucleophilic attack of the enolate (Aldol addition), and deprotonation of the α-
hydrogen losing the hydroxyl group forming a conjugated compound, benzalacetone. With the
presence of excess base, benzalacetone reacts with benzaldehyde under the same process to
form dibenzalacetone. The IR spectra show the presence of carbonyl compound and
monosubstituted aromatic ring. However, a hydroxyl group can be observed in the spectra
signifying the excess base that results in an experimental error. The product yield is 0.42 g
resulting to 36.88% yield. In the same principle, p-Anisaldehyde and methyl ethyl ketone are
reacted to form (1E, 4E)-1, 5-Bis (4-methoxyphenyl)-2-methyl-1, 4-pentadien-3-one. However, the
product resulted in a mixture with unknown impurity which can be hardly isolated using some
separation techniques. As a result, the product remains a mixture.

Keywords: a Aldol addition, Aldol condensation, dibenzalacetone, enolate ion

INTRODUCTION
For compounds having carbonyl group, carbons are
designated using Greek letters (α, β, γ, δ) to establish
their proximity to the carbonyl atom. The hydrogen
atoms are called based on the carbon they are
connected to such as alpha hydrogen on alpha
carbon. (Klein, Alpha Carbon Chemistry: Enols and
Enolates, 2013)
Figure 1. Greek letters representing carbon atom
beside carbonyl atom
Alpha carbon is the first carbon adjacent to the
carbonyl atom. Due to the electron-withdrawing
nature and resonance structure of the carbonyl group,
the alpha carbon is considered to be highly acidic.
This acidity makes it easy to be deprotonated to form
enolate and enols. (Reactions at the a-carbon in
carbonyl compounds)
Enol is a combine word of alkene ‘en’ and alcohol ‘ol’.
Enolate, on the other hand, is an enol with ionic
charge. Enols are formed by tautomerization of the

carbonyl group under either acidic or basic
conditions.
Scheme 1. Reaction mechanism for carbonyl to enol
Under acid-catalyzed tautomerization, the reaction
proceeds via (refer to Scheme 14): a) proton transfer
of the acid to the carbonyl oxygen to activate the
carbonyl group; b) the compound resonates to form a
more resonance-stabilized cation called enolate; and
c) deprotonation of the alpha hydrogen to form enols.
For basic-catalyzed tautomerization (refer to Scheme
15), the reaction proceeds by: a) deprotonation of the
alpha hydrogen by the base; b) the intermediate
resonates to form enolate; and c) protonation of the
oxygen to form an alcohol moiety.
The keto-enol tautomerization occurs at equilibrium.
Normally, the equilibrium favors the carbonyl
tautomer due to its stability. Although, there are cases
where the enol tautomer is favored due to the
following:
 Aromaticity. The enol tautomer is favored due
to aromatic stabilization.
Figure 2. Effect of aromaticity in equilibrium of keto-
enol tautomerization
 Hydrogen bonding. Hydrogen bond acceptors
stabilized the enol form due to internal
hydrogen bonding stabilization
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SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION
Figure 3. Effect of Hydrogen bonding in equilibrium of
keto-enol tautomerization
Some other minor factors that affect the equilibrium
includes the solvent utilized in the reaction,
conjugation of the pi bonds and more substitution
present in a ring assuming that steric effect is
minimal. (Ashenhurst, 2019)
The addition of enols and enolates to the carbonyl
group is a process for aldol addition reaction. Aldol,
from aldehyde ‘al’ and alcohol ‘ol’, is considered as
the end product of the aldol additions. This reaction is
a good step in forming a new C-C bond formation.
The stepwise mechanistic process is as follows:
(Klein, Alpha Carbon Chemistry: Enols and Enolates,
2013)
 The reaction starts with enolate formation
(refer to Scheme 15)
 Nucleophilic attack of the of the enolate anion
to the carbonyl group to form an alkoxide
anion (refer to Scheme 16)
 The alkoxide anion is then protonated to form
the aldol product (refer to Scheme 17)
However, the equilibrium favors the precursor of the
aldol product due to the steric hindrance of the
carbonyl oxygen and hydroxyl group. To favor the
product formation, aldol condensation is performed.
During this process, the hydroxyl group is protonated
to form an oxonium ion, and then later dehydrated to
form a conjugated unsaturated carbonyl system
called enal (alkene aldehyde) or enone (alkene
ketone). The conjugation makes the product more
stable, thus more favored.
The mechanism for aldol condensation is as follows
(refer to Scheme 18):
 Deprotonation of the alpha carbon of the
aldol addition product

 The alkoxide anion resonates losing the
oxonium cation forming a conjugated pi
system
One good example of aldol condensation is the
synthesis of dibenzalacetone from benzaldehyde (two
equivalents) and acetone (one equivalent). These
reactions proceeds by forming benzalacetone then
reacts with benzaldehyde to form Dibenzalacetone.
(Kokv, 2011)
Scheme 2. Mechanism for Dibenzalacetone
The IR spectra of dibenzalacetone is as follows:
(chegg.com)
Figure 4. IR spectra of dibenzalacetone
On the other hand, crossed aldol condensation
focuses on two different reactants undergoing aldol
reactions such that a mixture is a possible product.
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SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION
EXPERIMENTAL SECTION
Chemical Reagents and Apparatuses
The experiment is divided into two parts: a) Synthesis
of dibenzalacetone and b) Synthesis of (1E, 4E)-1, 5-
Bis (4-methoxyphenyl)-2-methyl-1, 4-pentadien-3-
one.
On synthesis of dibenzalacetone, the reagents
needed are benzaldehyde (2 equivalents), acetone (1
equivalent), sodium hydroxide (base), 95% ethanol
(solvent) and cold water.
Table 1. Reagent table for synthesis of Dibenzalacetone
On the second part, the reagents needed are p-
Anisaldehyde (2 equivalents), methyl ethyl ketone (1
equivalent), potassium hydroxide (base), 95% ethanol
(solvent), ice-cold 95% ethanol, glacial acetic acid
and toluene or 2-propanol.
Table 2. Reagent table for synthesis of (1E, 4E)-1, 5-Bis (4-
methoxyphenyl)-2-methyl-1, 4-pentadien-3-one
Each reagents exhibits harmful effects when handed
improperly. Personal protective equipment should
highly be observed when handling the chemicals.

The materials needed are vial, Erlenmeyer flask,
Buchner funnel, magnetic stirrer, hot plate and funnel
and filter paper.
Methodology
The first part of the experiment, where
dibenzalacetone is synthesized, proceeds by mixing
benzaldehyde and acetone in an Erlenmeyer flask.
The volume used is as follows calculated based on
the given mole equivalencies of the reactants.
Table 3. Scale of the reactants
The solution is then added with 5mL sodium
hydroxide (5 molar) and 5 mL 95% ethanol. The
solution is capped and stirred for about 30-45 minutes
until precipitates formed. The precipitate formed is
collected by vacuum filtration and recrystallize using
95% ethanol as solvent. The dried product is weighed
to determine the percent yield.
On the second part of experiment, p-Anisaldehyde
and methyl ethyl ketone are prepared using the
calculated volume from the given mole equivalency.
(Scale: 1 mL aldehyde)
Table 4. Scale for the designated aldehyde and ketone
P-Anisaldehyde is mixed with 95% ethanol until the
solution is homogenous. The 8.75 mL of the base,
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SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION
which is of potassium hydroxide (2 molar), is then
added to the solution. Afterwhich, the methyl ethyl
ketone is added until the formation of precipitate. The
precipitate is isolated by vacuum filtration then later
rinsed with 10% acetic acid to neutralize the possible
presence of excess base. The product is air-dried and
weighed for percent recovered.
Results and Discussions
The synthesis of benzalacetone occurs via reaction of
benzaldehyde (as the aldehyde) and acetone (as the
ketone) using sodium hydroxide as a base.
The first reaction of the experiment deals with the
deprotonation of the alpha-hydrogen of the acetone
forming an enolate anion.
Due to the electron withdrawing property of the
carbonyl oxygen and resonance structure of the
carbonyl group, the alpha-hydrogen of the acetone is
considered to be highly acidic which can readily be
deprotonated by sodium hydroxide, a base. Under
basic condition, the formation of enol proceeds via
deprotonation of the α-hydrogen where enolate is
formed.
Scheme 3. Formation of enolate anion from acetone
This enolate anion can now attack due to its strong
nucleophilicity. As the aldehyde carbonyl is more
reactive than the ketone, the anion reacts with the
carbonyl group forming a hydroxyl ketone, in our
case, is 4-Hydroxy-4-phenyl-2-butanone.
Scheme 4. Nucleophilic attack of the enolate anion
 SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION

Scheme 5. Protonation of the alkoxide

Scheme 9. Formation of conjugated enone

The Aldol addition product, 4-Hydroxy-4-phenyl-2-
butanone, is unstable due to the steric hindrance of The amount of the product recovered is 0.42 g out of
the hydroxyl group and carbonyl oxygen. As a result, the theoretical 1.139 g. These results in 36.88%
the reaction proceeds to Aldol condensation where percent recovered. In comparison with the other
the base deprotonates the α-hydrogen, which is more groups, the tabulated actual and percent yield is as
acidic due to the presence of two oxygen atom. follows:
Therefore, the hydroxyenolate intermediate resonates
losing the hydroxyl group to form a conjugated enone,
in this case, called benzalacetone which is more
stable.

Scheme 6. Formation of benzalacetone

The formation of a conjugated enone is more stable Table 5. Actual and Percent yield for dibenzaldehyde synthesis
than that of the precursor, thus, the reaction favors
the product formation. Moreover, the conjugation
To verify the presence of the enone in the product, IR
makes the compound highly stable because the
spectra test is utilized.
alkene is conjugated not only to the carbonyl group,
but of benzene ring also.
Due to the presence of excess benzaldehyde, the
benzalacetone reacts again to form a
dibenzalacetone.

Figure 5. IR spectra of starting material, benzaldehyde

Scheme 7. Formation of enolate anion

Scheme 8. Nucleophilic attack of enolate anion

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 SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION

Scheme 11. Nucleophilic attack of enolate

Figure 6. IR spectra of the product, dibenzalacetone

The hydroxy-ketone formed is unstable due top steric
hindrance of the two oxygen atom. In effect, the
reaction proceeds to Aldol condensation.
The strong stretch peaks in 1650.42 cm -1 shows the
presence of the carbonyl (C=O) compound in the
product. The peaks around 3054-3026 cm-1 show the
presence of alkene functional group. These two
stretch peaks can be observed in both starting
material and the product. Below 1500, we can
observe that the presence of conjugated alkenes of
product is more than that of the starting material.
Moreover, we can also observe the presence of
Scheme 12. Formation of the conjugated bond
hydroxyl group in the product which can possibly
signifies the presence of impurities.
The conjugated enone is far more stable than the
The formation of dibenzalacetone begins by precursors utilized in this reaction, thus, would favor
deprotonating the α-hydrogen of ketone with base, product formation. The excess p-Anisaldehyde would
nucleophilic addition of enolate, eliminating the then react again to form the product.
hydroxyl group to from a conjugated enone. This
process follows the principle of Aldol addition and
Aldol condensation.
This two Aldol process can also be utilized in the
reaction of p-Anisaldehyde and methyl ethyl ketone.
The α-hydrogen of ketone would be deprotonated to
form an enolate.

Scheme 13. Formation of the product

The actual amount recovered is 20.72 out of 1.305

Scheme 10. Formation of enolate
(theoretical). Errors occur in the dissolving the
compound and remaking the synthetic route due to
Enolate is a good nucleophile and can attack the the properties of the reactant.
carbonyl group, p-Anisaldehyde, to form a hydroxy-
ketone.
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 SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION

CONCLUSION: Ashenhurst, J. (2019, March 26). Enols and Enolates.

The synthesis of dibenzalacetone proceeds via
reaction of acetone and excess benzaldehyde
through the process of deprotonation the alpha
hydrogen forming an enolate ion, nucleophilic attack
of the enolate (Aldol addition), deprotonation of the
alpha hydrogen losing the hydroxyl group to form a
conjugated bonding (Aldol condensation) for more
stable product. The product of Aldol addition cannot
be isolated due to the instability brought by the steric
hindrance of the hydroxyl and carbonyl oxygen. In
effect, Aldol condensation is performed to form a
conjugated bonding which is more stable. Moreover,
the conjugation of the product makes it highly stable
because the conjugation exists not only on the alkene
to carbonyl group but also to benzene ring.
Retrieved from Master Organic Chemistry.
chegg.com. (n.d.).
Klein, D. (2013). Alpha Carbon Chemistry: Enols and
Enolates. In D. Klein, Organic chemistry, 2e
(pp. 1044 - 1068). Wiley.
Kokv, G. (2011, November 16). Synthesis of
Dibenzalacetone by Aldol Condensation.
Retrieved from One Part of Chemistry.
Parkinson, D.-R. (2014). Analytical Derivatization
Techniques. Reference Module in Chemistry,
Molecular Sciences and Chemical
Engineering.

Reactions at the a-carbon in carbonyl compounds.

As excess benzaldehyde is used, the product (n.d.). Retrieved from Faculty Pages:
(benzalacetone) will react again with benzaldehyde www.faculty.umassd.edu
through enolate formation, Aldol addition, and Aldol
condensation to form a dibenzalacetone. The Smith, B. C. (n.d.). The C=O Bond, Part VI: Esters
presence of the carbonyl group with monosubstituted and the Rule of Three. Spectroscopy.
aromatic ring can be observed in the IR spectra of the
product. However, the presence of hydroxyl group Z, E. (2015, December 23). Retrieved from Socratic
can be observed which signifies impurities. The Q&A.
actual yield of the product is 0.42 g with 36.88 % yield
. Errors occurred on the stirring process as excess
base is used making the product to be more in liquid
state that the desired solid (precipitate) as the base
continuously dissolving the supposed precipitate
formed. The hydroxyl group in the product may signify
SUPPORTING INFORMATION
the presence of excess base.

On the other hand, the same principle is used in the Mechanism for enolization at two separate conditions:
reaction of p-Anisaldehyde and methyl ethyl ketone.
Formation of enolate, Aldol addition and Aldol
condensation are the mechanistic process involved in
the synthesis. However, the problem occurs when the
product contains undetected impurity which cannot be
easily removed by some separation techniques. As a
Scheme 14. Acid-catalyzed enolization
result, the product remain impure.

REFERENCES:

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 SYNTHESIS VIA ALDOL AND MIXED ALDOL CONDENSATION

Scheme 15. Base-catalyzed enolization

The Aldol addition mechanism is as follows:

1. Enolate formation (refer to Scheme 15)

2.
Scheme 16. Formation of alkoxide anion

3.
Scheme 17. Formation of aldol addition product

The Aldol condensation mechanism process is as follows:

Scheme 18. Aldol condensation mechanism