Title: Aldol Condensation Reaction

Objectives:

1. To synthesize p-methoxybenzalacetophenone from p-methoxybenzaldehyde and

acetophenone with Aldol condensation reaction.

2. To purify the product by crystallization

Introduction

Carbonyl compounds are everywhere. In additon to their uses as reagents and

solvents, they are constituents of fabrics, flavorings, plastics and drugs. Naturally
occuring carbonyl compounds include proteins, carbohydrates and nucleic acids that
make up all plants and animals (Wade 2014).
The aldol condensation is a reaction that involves two carbonyl compounds to be
condensed together to give a new carbon-carbon bond, which is a double bond. This
reaction is used extensively in organic synthesis to build large molecules from smaller
ones. When an α-carbon of the first carbonyl molecules become attached to the
carbonyl carbon of the second, a product known as the Aldol product is formed. This
product can react further with base to lose water and give an α,β-unsaturated
aldehyde ( or ketone).
However, dehydration generally occurs under slightly more vigorous conditions,
such as higher temperature, compared to the condensation reaction. Thus at higher
temperatures and under basic conditions, the Aldol reaction will go directly to the
conjugated enone without any isolation of the Aldol intermediate. Aldol products can
be formed through either acidic or basic conditions and since they are usually
exothermic the reaction will be driven to completion.
P-methoxybenzaldehyde is a compound with a molecular formula of C8H8O2
and consists of a benzene ring with an aldehyde and methoxy functional group
attached to it. It is found in fennel and anise plants naturally and exists as a clear to
slightly yellow liquid at room temperature. It is soluble in alcohol and ether and is
most often used in the fragrance and perfume industry due to its aroma.
P-methoxybenzaldehyde and its derivatives are also often used in chemical reactions
as intermediates to obtain products such as dyes and agrochemicals and also used in
preparation of other organic compounds such as pharmaceuticals.
Apparatus and materials
Conical bottom flask
Beaker
Pasteur pipette
Filtering flask
Glass rod
Suction glass funnel
Three-way pipette rubber bulb

Chemicals
P-Methoxybenzaldehyde
Acetophenone
Ethanol
Sodium hydroxide (60% NaOH)

Procedure

1. 0.27 g or 0.24 ml (2mmol) of p-methoxybenzaldehyde, 0.28 g or 0.18 ml (2.4mmol)

of acetophenone and 0.8 ml of ethanol have been placed in 5-ml conical bottom flask.
The mixture has been stirred well with a glass rod.
2. 0.2 ml 0f 60% NaOH was added and the mixture was stirred for another 5 minutes.
3. A colour change of the mixture and a precipitate beginning to appear were
observed. 2 ml of cool water has been added into the mixture. Stir well. The mixture
was poured into a small beaker containing 3 ml of cold water and stir vigorously.
4. The produst was collected by suction filtration. The product was washed with cool
water and continue suction to air-dry.
5. The melting point of the product was determined.
6. The rest of the product was recrystalized from ethanol. The crystals was filtered by
suction filtration as described in step 4.
7. The crystals of the product was weighed and its melting point was determined
compared to the previous one.
 Clean up
1. The aqueous filtrate has been neutralized with the acetic acid before flushing them
down the drain with copious amount of water.
2. Waste ethanol has been poured into the appropriate waste container.

Results:

Sample Appearance Melting Moleular Weight Mole Volume

point/Boiling Weight (g) (mmol) (mL)
point (°C)
p-methoxybenzaldeh Slightly 0/248 136.148 0.27 2 0.24
yde yellow
Acetophenone Slightly 19 – 20/202 120.15 0.28 2.4 0.28
yellow
Ethanol Colorless -114/78.37 46.07 0.63 14 0.80
Sodium hydroxide Slightly 318/1388 39.99 0.426 11 0.20
yellow
p-methoxybenzaacet Yellow 69-74 238.28 0.85 2 -
ophenone

Before recrystallization
Mass of product + filter paper + petri dish: 10.61 g
Mass of filter paper : 0.03 g
Mass of petri dish : 9.72 g
Mass of product : 0.86 g
Appearance of the crude mixture : Oily yellow
Melting point range : 70.76°C

After recrystallization
Mass of product + filter paper + petri dish: 9.87 g
Mass of filter paper : 0.04 g
Mass of petri dish : 9.44
Mass of product: 0.39 g
Melting point range : 89.90°C
Percentage yield
[Mass of pure sample / mass of impure sample]% = [0.39g / 0.86 g] % = 45.35%

Discussion

Aldol condensation reaction is the name given to an organic reaction of an enol or

enolate ion with a carbonyl compound, resulting in the formation of a
β-hydroxyketone or β-hydroxyaldehyde. This is succeeded by a dehydration that gives
a conjugated enone. The process is also simply known as Aldol reaction. It is an
example of electrophilic replacement at the alpha carbon present in enolate or enols
anions.

The name of this process comes from the fusion of two words, “Aldol” and
“Condensation”. The term “Aldol” refers to a colorless, oily liquid produced due to
the condensation of two acetaldehyde molecules. The substance manufactured in this
way consists of an aldehyde group (-CHO) and an alcohol group (-OH). The word
“Condensation” means a reaction characterized by the combination of two molecules
to produce a larger product accompanied by the loss of a water molecule.

In this experiment, P-methoxybenzaldehyde is a compound with a molecular

formula of C8H8O2 and consists of a benzene ring with an aldehyde and methoxy
functional group attached to it. It is found in fennel and anise plants naturally and
exists as a clear to slightly yellow liquid at room temperature. It is soluble in alcohol
and ether and is most often used in the fragrance and perfume industry due to its
aroma. P-methoxybenzaldehyde and its derivatives are also often used in chemical
reactions as intermediates to obtain products such as dyes and agrochemicals and also
used in preparation of other organic compounds such as pharmaceuticals.
Acetophenone exists as a clear to yellow liquid or crystals and is the simplest
aromatic ketone. It has a molecular formula of C6H5COCH3.
 It can be obtained through the Friedel-Crafts process by reacting benzene with
acetyl anhydride or alternatively acetyl chloride for commercial uses. Like
p-methoxybenzalacetophenone, it can also be used as an intermediate in chemical
reactions to obtain pharmaceuticals and other organic products. Acetophenone and its
derivatives are also used in fragrances like perfumes and soaps.
methoxybenzalacetophenone exists as a yellow crystalline powder in room
temperature and can be used to produce
3-(4-methoxy-phenyl)-3-morpholin-4-yl-1-phenyl-propan-1-one by reacting with
morpholine. It is usually prepared through aldol condensation between
p-methoxybenzaldehyde and acetophenone, which is what was conducted in this
experiment. NaOH was added to the reactants and the reaction was performed under
vigorous conditions, allowing dehydration to occur and the enone product to be
formed without an intermediate.

The crude product then under went recrystallization for purification purposes. The
crude product will be dissolved in a solvent and undergo gentle boiling and after
complete dissolution the solution will be cooled to room temperature. The crystals
will reform again after being cooled down, which will be purer than the crude crystal
product. The mechanism of the synthesis of p-methoxybenzalacetophenone can be
illustrated as follow:

O O-
O

CH2 + H2O
CH2 CH2

H
OH-

The condensation reaction is a base-catalysed aldol condensation due to the use of the
base, NaOH. The partial deprotonation of the acetophenone produces a low
equilibrium concentration of the enolate anion which will be served as the
nucleophilic site for the reaction.
 O
O O
O-

CH2 H

OMe

OMe

Next, the addition step occurred in slow rate, which will be the rate-determining step
of the process.
O
H
H
O- O
OH O

MeO +
MeO

OH-

The nucleophilic site will protonates and produces the hydroxide ion, which will be
used as the catalyst.

OH O
H OH O
H

H
MeO
MeO
OH-

H O

H
MeO

Finally, the β-hydroxy carbonyl will undergo dehydration and produce the α,
β-unsaturated ketone, which is the p-methoxybenzalacetophenone.

The summary of the reaction of this condensation reaction can be described as follow:
 H O
O O

NaOH
H + H3C
H2O
H
MeO
MeO

p-Methoxybenzaldehyde Acetophenone p-Methoxybenzalacetophenone

From this experiment, the percentage yield of the compound was 45.35%, and this
show us that the product still have impurities. The presence of impurities can be
decreased by careful handling of suction filtration. Make sure that all the solid is fully
filtered without any traces. Sodium hydroxide is hygroscopic in nature. The vial
should be capped immediately after every use. Do not over heat it in the
recrystallization process, because over heating may cause a black tar substance that is
due to the decomposition of our product to form.

Questions
1. Show the mechanism of the synthesis of p-methoxybenzalacetophenone in this
experiment.

First step is the base-catalysed formation of enolate anion.

O O-
O

CH2 + H2O
CH2 CH2

H
OH-

Second step is the aldol addition of enolate to carbonyl, which is the rate determining
step.
 O
O O
O-

CH2 H

OMe

OMe

O
H
H
O- O
OH O

MeO +
MeO

OH-

The third step is the irreversible base-catalysed dehydration of addition product.

OH O
H OH O
H

H
MeO
MeO
OH-

H O

H
MeO
2. Will there be any difference in using m-nitrobenzaldehyde as a starting
material instead of p-methoxybenzaldehyde? Explain.
The function of m-nitrobenzaldehyde will give a higher yield in the synthesis of aldol
product. This is because introducing the electron-withdrawing groups onto aromatic
aldehydes favors the nucleophilic addition of a ketone enolate to the aldehydes to
form the aldol products. Therefore, the aldol condensation process will run efficiently,
giving the corresponding product α,β-unsaturated ketones in excellent yields (close to
100%).

Conclusion:
Froom this experiment we are know p-Methoxybenzalacetophenone can be
synthesized via aldol condensation reaction which involves two carbonyl starting
materials, which is the acetophenone and p-Methoxybenzaldehyde. The mechanism of
the aldol condensation reaction will give a synthetic idea on the synthesis of the aldol
product. The purification of the aldol product can be done via recrystallization to get a
higher percentage yield.

References
1. McMurry, J. 2008. Organic chemistry. Pacific Grove, CA: Brooks/Cole Pub.

2. Wade, L. G. 2014. Organic chemistry. Upper Saddle River, NJ: Prentice Hall.

3. Kalsi, P. S. 2006. Organic reactions stereochemistry and mechanism: Through

solved problems. New Delhi: New Age International (P) Limited.