Synthesis of Aspirin

Eryll Paolo Alea, Patrick Jerome Asutria, Nadine Joy Baccay, Charize Ann Buenavista, Stephanie Dawn Buted, Rafael James
Cabanting
Group # 1, 2F-PH, Department of Pharmacy, University of Santo Tomas

ABSTRACT
Acetylsalicylic acid (C9H9O4), or most commonly known as Aspirin, is one of the most popular
medicine used for it can cure many diseases. This includes its ability to be an antipyretic (reduces fever),
analgesic (reduces pain without producing anesthesia or loss of consciousness), anti-inflammatory
(relieve the pain and swelling with association to arthritis and rheumatism), uricosuric (enhances the
elimination of uric acid), and interfere with the bodys production of prostaglandins and their products
(thromboxanes), which are associated with headaches, platelet aggregation, and vasoconstriction.
Aspirin was the first non-steroidal anti-inflammatory drug to be discovered and is a derivative of
salicylate, which can be found in plants such as willow trees and myrtle. The synthesis of Aspirin aims
to explore the chemical processes in the synthesis of aspirin and to calculate for the percentage yield of
aspirin.

INTRODUCTION
Salicylic acid (C7H6O3) is a fine white and
odorless crystal. It is found and extracted in
plants such as willow trees and myrtle and is
commonly used as an analgesic and an
antipyretic. It has long been used in Europe and
China for the treatment of these conditions after
Hippocrates, Galen, Pliny the Elder and others
have discovered that willow bark could ease
aches and pains and reduce fevers.
The IUPAC Name of Salicylic acid is 2Hydroxybenzoic acid. Its boiling point is 211C
and its melting point is 159C. The density of
salicylic acid is 1.44 g/mol. Salicylic acid is
very reactive in moisture, light, heat, and
incompatibilities such as iron salts, lead acetate,
iodine and nitrous ether. It is used in medicine
such as making aspirin and used as constituents
of rubefacient products such as methyl
salicylate, used a liniment to soothe joint and

muscle pain and choline salicylate, used

topically to relieve the pain of mouth ulcers.
Acetic anhydride (C4H6O3) is a clear colorless
liquid with a strong odor of vinegar. It is the
simplest isolable anhydride of a carboxylic acid
and is widely used as a reagent in organic
synthesis. The boiling point of acetic anhydride
is 140C and the melting point is -73C. Its
density is 1.082 g/ml in liquid state and its
molecular weight is 102.09 g/mol. It is mainly
used for acetylations leading to commercially
significant materials. Also, the largest
application of acetic anhydride is for the
conversion of cellulose to cellulose acetate,
which is a component of photographic film and
other coated materials. It is also used in the
production of aspirin which is prepared by the
acetylation of salicyclic acid.

The objective of this experiment is (1) to

explore the chemical process in the synthesis of
aspirin and (2) to calculate for the percentage
yield of aspirin.
Crystallization is a technique which is use to
purify solid compounds. It is a process of
crystal formation in a solution. Organic
compounds that are solid in room temperature
are usually purified by crystallization.
Crystallization is based on the principles of
solubility: compounds (solutes) tend to be more
soluble in hot liquids (solvents) than they are in
cold liquids. If a saturated hot solution is
allowed to cool, the solute is no longer soluble
in the solvent and forms crystals of pure
compound. Impurities are excluded from the
growing crystals and the pure solid crystals can
be separated from the dissolved impurities by
filtration.
METHODS
To synthesize aspirin, the acetic anhydride was
reacted with salicylic acid. First, 2.00 g of
salicylic acid was weighed out in a watch glass
and transferred into a 20-cm test tube. Then,
5.00 mL of acetic anhydride was dispensed into
the test tube followed by the addition of 5 drops
of concentrated sulfuric acid (H2S04). The
mixture was then stirred until the salicylic acid
dissolved completely using a stirring rod. Then,
a 250-mL beaker filled with three-fourths full of
tap water was brought to boil. The beaker was
heated using a Bunsen burner and is placed on
top of it with the aid of a ring stand. After that,
250-mL plastic wash bottle was filled with
distilled water and packed in ice contained large
beaker. When the water in the beaker begun to
vigorously boil, the burner was turned off and
the test tube was clamped in the hot water bath
with the aid of a iron clamp. Then, the contents
of the test tube were stirred for about a minute.
The reaction mixture was allowed to remain in

the water bath heated at a range of 70-80

degrees Celsius for 20-30 minutes. The test tube
was removed from the water bath and then the
contents of the test tube were cautiously poured
onto 5 mL of water in a 150-mL beaker. After
the reaction inside the beaker had subsided, the
mixture was stirred for a minute then slowly
added room temperature water, a few drops at a
time, until a maximum of 40 drops had been
added or until the solution became cloudy. The
solution became clear again, that is why
addition of water was continued until a cloud of
small crystals of aspirin reappears. The crystals
appeared in the beaker so the test tube was
rinsed with small volumes of ice-cold water
from the wash bottle, adding the rinse to the
solution in the 150-mL beaker. Then 20 mL of
ice cold water was measured and added into the
150-mL beaker. After which, it was stirred and
then the beaker was packed in ice for at least 10
minutes to allow the aspirin to crystallize. The
crystals were filtered using a pre-weighed filter
paper and allowed to dry overnight. Lastly, the
weight of dried aspirin was measure and the
percentage yield was computed.
For the ferric chloride test for salicylic acid, first
1 mL of water was added to each of 6 clean 10cm test tubes. Microspatula was used to place a
crystal of salicylic acid into the first test tube,
powdered commercial aspirin into the second,
synthesized aspirin into the third, benzoic acid
into the fourth, and 1 mL of benzyl alcohol into
the fifth. Nothing is to be added to sixth test
tube, which will act as the control. Then, the test
tubes were shaken to dissolve the solid and 2%
aqueous solution of ferric chloride was dropped
with a Pasteur pipette. The colors produced
were observed and then an inference was
written based on the findings.
For the starch test, 2 mL of water was added to
each of the three 10-cm test tubes. Then, to the
first test tube, a small amount of the synthesized

aspirin was added. To the second, nothing was

added for it acted as a control. To each of the
test tube, a drop of iodine solution was added. A
blue or black color will indicated the presence
of starch. The color produced was observe and
an inference was written based on the findings.
The last test conducted for this experiment was
the preparation of methyl salicylate. Methyl
salicylate was prepared in a manner similar to
Weight of watch
95.0 g
glass + salicylic
acid
Weight of empty
93.0 g
watch glass
Weight of salicylic
2.0 g
acid
Volume of acetic
5.00 mL
anhydride
Volume of
5 drops
concentrated
sulfuric acid
Weight of filter
6.0 g
paper + product
Weight of dry
3.0 g
filter paper
Weight of product
3.0 g
aspirin but a lower temperature. 1.00 g of
salicylic acid was weighed out exactly and
placed in a 20-cm test tube. Then, 5 mL of
methyl alcohol was added and also 3 drops of
concentrated sulfuric acid (H2S04).

MATERIALS
The materials used in this experiment are the
following:

In the reaction of salicylic acid and acetic

anhydride, the hydroxyl group (OH ) on the

For the reaction of acetic anhydride and

salicylic acid, the materials used were 20-mL
test tube, 150-mL beaker, tap water, ice, bunsen
burner (for heating), iron ring and clamp,
stirring rod (for stirring the mixtures and
solutions), 250-mL wash bottle and lastly the
two main components which are the acetic
anhydride and salicylic acid.
For the ferric chloride test for salicylic, the
materials used were 10-cm test tubes,
microspatula, salicylic acid, powdered
commercial aspirin, synthesized aspirin, benzoic
acid, 1 mL benzyl alcohol, 2% aqueous solution
of ferric chloride and Pasteur pipette.
For the starch test, the materials used were 10cm test tubes, synthesized aspirin and iodine
solution.
For the preparation of methyl salicylate, the
materials used were salicylic acid, test tube,
methyl alcohol, concentrated sulfuric acid,
water, beaker and hot plate (for water bath).
RESULTS AND DISCUSSIONS
TABLE 1. Reaction of Acetic Anhydride and
Salicylic Acid

Illustration of the Synthesis of

Acetylsalicylic acid

benzene of the salicylic acid reacted with acetic

anhydride to form an ester functional group.
Thus, the formation of acetylsalicylic acid is
called as an esterification reaction. Esterification
is a reaction wherein refluxing of the carboxylic

group and the primary or secondary hydroxyl

group occurs to prepare an ester. This reaction
requires the presence of an acid catalyst which
was is the sulfuric acid in the experiment.

Theoretical yield:
2.0081 g C 7 H 6 O 3

1 mol
180.

138.12 g C7 H 6 O3 1 mol C

Percentage yield:

To calculate for the actual yield of the

synthesized aspirin, the limiting reagent must
first be identified. Based from the calculations
made, salicylic acid was found out to be the
limiting reagent for it yielded a smaller value
than acetic anhydride. Thus, the theoretical yield
is based from and also equal to the value of the
limiting reagent. This is determine if the
experiment conducted obtained a complete
reaction from the acetic anhydride and salicylic
acid. Based from the calculations, 115% was
synthesized aspirin, thus it had slight impurities
which were later on confirmed using the ferric
chloride test.
Calculations:
Chemical reaction:

3.0 g synthesized aspirin

100=115
2.6082 g C 9 H 9 O4

TABLE 2. Ferric Chloride Test

Test Tube
Salicylic Acid
Commercial
Aspirin
Synthesized
Aspirin
Benzoic acid
Benzyl
alcohol
Control

Observations
Purple
solution
N/A

Inference
Presence of
Salicylic acid
N/A

Purple
solution
Turbid white
solution
Colorless

Presence of
Salicylic acid
Absence of
Salicylic acid
Absence of
Salicylic acid
Absence of
Salicylic acid

Colorless

C7 H 6 O3+C 4 H 6 O3 C 9 H 9 O4 +CH 3 COOH

Limiting reagent:
Acetic anhydride:
5.00 ml C 4 H 6 O3

1.082 g
1 mol
180.16 g

=9.55 g C9 H 9 O 4
1ml
102.09 g C4 H 6 O3 1 mol C9 H 9 O 4

Illustration of the Reaction of Ferric Chloride

Test for Salicylic acid wherein yellow color
Salicylic acid:
indicates the ferric ion and purple color
1 mol
180.16
g
indicated
the reacted
acid.
2.0081 g C 7 H 6 O 3

=2.61
C 9 H 9 Osalicylic
4
138.12 g C7 H 6 O3 1 mol C 9 H 9 O4

According to the results of the test conducted

Salicylic acid and Synthesized salicylic acid
were found to have the presence of salicylic
acid, which was indicated by the purple
coloration of the solution. While the Benzoic
acid, Benzyl alcohol and the control had the
absence of the salicylic acid.

iodine which leaves to the inference that there is

no starch present both to the synthesized aspirin
and the control. However, even if we did not
conduct the experiment with the commercial
aspirin, the expected result was a formation of a
blue-black colored solution which indicates a
positive result.

Thus, this test is used for determination of

purity of a substance. The purple color produced
is caused by the reaction of salicylic acid with
aqueous ferric

( Fe ( H 2 O )6+3 )

ion. The oxygen

atoms of the carboxylic acid group

(COOH ) and hydroxyl group (OH ) on
salicylic acid can form a complex group with
ferric

( Fe ( H 2 O )6+3 )

ion which indicates the

presence of salicylic acid. . In aspirin, the

hydroxyl group (OH ) was replaced by ester

(OCOC H 3) during the process of

esterification and nucleophilic substitution
which prevents the complex formation. This
will yield a yellow solution. However, the
synthesized aspirin reacted in ferric chloride
which implies that salicylic acid is present.
Thus, there are certain impurities in the obtain
aspirin.
TABLE 3. Starch Test
Test Tube
Synthesized aspirin
Control

Observations
Clear colorless
solution
Light yellow solution

Starch is one of the inert binding materials used

in the production of aspirin tablets. Synthesized
aspirin did not reacted with iodine that is why
there was no formation of a blue-black colored
solution. The control did not also reacted with

Illustration of the Preparation of Methyl

Salicylate
Methyl salicylate is a methyl ester of salicylic
acid, commonly called oil of wintergreen. It
has two main functional groups which is the
ester and phenol. Methyl salicylate is also
prepared through the process of esterification
just like the acetylsalicylic acid. Thus, methyl
alcohol was used to dissolve the salicylic acid
and was subjected to water bath afterwards. It
produced a distinct mint-like odor which
confirmed the presence of methyl salicylic acid.
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Retrieved November 30, 2015 from
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