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Synthesis of Aspirin (Acetylsalicylic acid)

Authors: ABESAMIS, M., ACOSTA, M., AGUSTIN, F., *AQUITANIA, M.,


BAGSICAN, M.

Abstract
Acetylsalicylic acid , known as Aspirin, is one of the popular and
versatile medicines that cure diseases. It is considered a powerful drug for
relieving pain (analgesic), reducing fever (antipyretic), and reducing swelling
(anti-inflammatory). The synthesis of acetylsalicylic acid is derived from
salicylic acid which can be extracted in willow trees and allowing it to react
with acetic anhydride and a catalyst through the principle of crystallization.

I. Introduction
Salicylic anhydride decomposes. The
acid is density of acetic anhydride is 1.082
a fine white g/ml in liquid state and its
crystal and molecular weight is 102.09 g/mol.
odorless. It is Acetic anhydride is most widely
extracted in used for the conversion of cellulose
willow and to cellulose acetate, which is a
poplar bark that component of photographic film
has been used and other coated materials. It is
as an analgesic Figure 1 Structural also known as acetyl ether.
for centuries. formula of Salicylic
The boiling Acid
point of
salicylic acid is 211°C and the
melting point is 159°C. 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, Figure 2 Structural formula of
lead acetate, iodine and nitrous Acetic anhydride
ether. It is used in medicine such Crystallization is one of the
as making aspirin and most used purifying methods in
pharmaceutical applications, organic experiments. It is a
including methyl salicylate. process of crystal formation in a
solution. Organic compounds that
Acetic anhydride is are solid in room temperature are
a colorless liquid with a pungent usually purified by crystallization.
vinegar-like odor when it reacts The substance to be purified is
with water to form acetic acid. The dependent to its solubility in
boiling point of acetic anhydride is change of temperature whether in
140°C and the melting point is a hot or cold solvent. It is the main
-73°C. It is soluble in ether, factor that affects crystallization.
chloroform and benzene. It is The substance to be crystallized
soluble in water when acetic should show the ideal solubility
behavior in solvent. A substance slowly and cautiously in 150-ml
can be purified when both the beaker filled with 5 ml distilled
desired substance and the impurity water. When the mixture subsided,
have similar solubility at its boiling the mixture was stirred in 1 minute
point temperature, and when the while a drop of room temperature
impurity represents only a small water was added at a time, until it
fraction of total solid. The desired reached a maximum of 40 drops or
substance will crystallize on the solution became cloudy. When
cooling, but the impurities will not. the solution became clear, a few
drops of water were added
The objectives obtained in dropwise until crystals of aspirin
this experiment are the following: reappeared. When there are no
(1) to be able to explore the crystals found, the inner walls of
chemical process in the synthesis the beaker was scratched gently
of aspirin; (2) and to calculate for using the stirring rod to induce
the percentage yield of the crystal formation. Once the crystals
synthesized aspirin. of aspirin appeared, the test tube
was rinsed with a small volume of
II. Methodology ice-cold water from the wash
To synthesize aspirin, a 250- bottle. A 20-ml of ice cold water
ml beaker filled with three-fourths was added into the 150-ml beaker
of tap water was subjected to boil. then the beaker was packed in ice
The beaker is supported by the for at least 10 minutes to allow the
iron ring and iron stand. A 250-ml aspirin to be crystallized. The
plastic wash bottle filled with aspirin crystals were filtered using
distilled water was packed ice a pre-weighed filter paper and it
which was placed in a larger was dried overnight. Then, dried
beaker. While boiling, exactly aspirin crystals were weighed.
2.00 g salicylic acid was tared in a
watch glass and it was transferred To test the purity of the
in a clean, dry 20-cm test tube. synthesized aspirin, it was
Exactly 5.00 ml acetic anhydride subjected to ferric chloride test for
was dispensed to the test tube and salicylic acid. 1 ml water was
5 drops of concentrated sulfuric placed in 6 10-cm test tubes. A
acid was added. The small amount of each sample was
mixture is stirred using a stirring added in every test tube using a
rod until the salicylic acid was microspatula. Salicylic acid was
dissolved. The burner was turned placed in the first test tube,
off when the water in the beaker powdered commercial aspirin in the
began to boil vigorously. The test second test tube, synthesized
tube was placed in a hot water aspirin in the third test tube,
bath to allow the mixture the react benzoic acid in the fourth test tube
within a temperature range of 70°C and 1 ml of benzoic acid in the fifth
to 80°C in 20-30 minutes. The test tube. The sixth test tube filled
content of the test tube was stirred with 1 ml water was the control
well in 1 minute. Then, the test used. The sample used was
tube was removed from the water dissolved in 1 ml water then a drop
bath and its contents were poured of 2% aqueous solution of ferric
chloride was added using a Pasteur
pipette. The observed color
produced was noted.

Another test of purity used


was starch test. A 2 ml of water
was placed in 3 10-cm test tube. A
small amount of each sample was
added in every test tube. The
powdered commercial aspirin was
placed in the first test tube and
salicylic acid in the second test Figure 3 Structural formula
of Aspirin (Acetylsalicylic The
tube. The third test tube with 2 ml
acid)
water was the control used. A drop
synthesized acetylsalicylic acid is
of iodine solution was added in
prepared by allowing salicylic acid
each test tube. The observed color
to react in acetic anhydride with a
produced was noted.
strong acid as a catalyst such as
concentrated sulfuric acid and
Methyl salicylate was
phosphoric acid. The principles in
prepared in a similar manner as
crystallization are applied to obtain
aspirin but at a lower temperature.
the desired product, aspirin. The
Exactly 1.00 g of salicylic acid was
difference in solubility of the
placed in a 20-cm test tube. A 5 ml
synthesized acetylsalicylic acid to
of methyl alcohol and 3 drops of
its mother liquor at a lower
concentrated sulfuric acid
temperature will crystallize to
was added to the test tube. The
obtain the desired substance. In
mixture is stirred until the salicylic
Table 1, the used materials and
acid is dissolved in alcohol. Then,
substances are presented with
the test tube was subjected in
their corresponding weight or
70°C water bath for 15 minutes.
volume. The weight and volume
The mint aroma produced inferred
were accurately measured using
the presence of methyl salicylate.
the apparatus.

III. Discussion
Table 1. Reaction of Acetic Anhydride and Salicylic Acid
Weight of watch glass + salicylic acid…….55.9455 g
Weight of empty watch glass………………....53.9374 g
Weight of salicylic acid…………...………….......2.0081 g
Volume of acetic anhydride……………………....….5.00 ml
Volume of concentrated sulfuric acid…...…….…....5 drops
Weight of filter paper + product ...…………..2.8310 g
Weight of dry filter paper....…………..…...……0.2000 g
Weight of product ...…………..…………………....2.6310 g

Figure 4 Synthesis of Acetylsalicylic acid

Salicylic acid has two anhydride reacts slowly with


important functional groups salicylic acid. A need for a catalyst
present, the carboxylic group and is required to hasten the reaction.
the phenol group. In the reaction In this experiment, concentrated
of salicylic acid and acetic sulfuric acid is used as the acid
anhydride, the hydroxyl group catalyst. The formation of ester is
on the benzene of the also referred as a nucleophilic
salicylic acid reacted with acetic substitution reaction wherein
anhydride to form an ester the catalyst attracts the of
functional group; thus, the hydroxyl group. The salicylic acid
formation of acetylsalicylic acid is becomes more negative that it will
referred to as an esterification attract the acyl group of
reaction. Esterification is a reaction the acetic anhydride. Since acetic
wherein refluxing of the carboxylic anhydride is polar, it has a partially
group and the primary or positive group and a partially
secondary hydroxyl group occurs negative group. The partially
to prepare an ester. This reaction positive acyl group attaches to the
requires the presence of an acid salicylic acid to synthesize
catalyst. It can be expressed by acetylsalicylic acid. The by-product
the H+ in the equation. Acetic of this reaction is acetic acid.
Figure 5 Hydrolysis of Aspirin (Acetylsalicylic acid)

When the reaction is crystallization process of


completed, unreacted salicylic acid acetylsalicylic acid. Upon cooling, it
and acetic anhydride will be was packed with ice, acetylsalicylic
present with the acetylsalicylic acid became insoluble as its
acid, acetic acid and the catalysts. solubility decreased and eventually
Crystallization method is used to formed the crystals. The crystals
purify the acetylsalicylic acid from were obtained in acetic anhydride,
other substances in the mixture. At the mother liquor. Ice-cold distilled
room temperature, the water was used in filtering to rinse
acetylsalicylic acid is insoluble in the mixture to obtain the desired
water. During heating when the substance, aspirin. The aspirin was
salicylic acid is subjected to warm dried overnight and weighed
water bath, it dissolves. This will accurately.
let the reaction of the mixture to
occur at a temperature range of To calculate for the actual
70°C to 80°C in 20-30 minutes. yield of synthesized aspirin,
Acetic anhydride is used as the limiting reagent should be
solvent in this experiment because identified first. In the calculations,
it has relatively low boiling during the limiting reagent in the reaction
heating. In the principle of le is salicylic acid. The theoretical
Chatelier, the presence of excess yield of acetylsalicylic acid will be
acetic anhydride forces the based on the limiting reagent. This
equilibrium towards the desired is to identify if the actual
product. Through heating the experiment obtain a complete
solution, there will be acceleration reaction of salicylic acid and acetic
of the reaction to approach anhydride. From the calculation,
equilibrium. Water is not used as a 100.45% was synthesized aspirin
solvent for this experiment which presents that the
because water may hydrolyze the demonstrated experiment has
obtain aspirin to decompose into slight impurities obtain. These
salicylic acid and acetic acid. After impurities refer to the presence of
transferring the mixture in the salicylic acid. Ferric chloride test
beaker, addition of ice-cold water clarifies the purity of the obtain
was done dropwise to form cloud of substance.
small crystals. This will hasten
Calculations:
Chemical Equation:

Limiting reagent:
Acetic anhydride:

Salicylic acid:

Theoretical yield:

Percentage yield:

Table 2. Ferric Chloride Test


Test Tube Observations Inference
Salicylic acid Purple solution (+) Salicylic acid present
Commercial Pink solution (–) No presence of salicylic
aspirin acid
Synthesized Purple solution (+) Salicylic acid present
aspirin
Benzoic acid Light orange solution (–) No presence of salicylic
(cloudy) acid
Benzyl alcohol Yellow oily solution (–) No presence of salicylic
acid
Control Light yellow solution (–) No presence of salicylic
acid

Figure 6 Reaction of Ferric chloride test


(Yellow – Ferric ion; Purple – Reacted salicylic acid)
Ferric chloride is used for
determination of purity of a
substance. The intense purple color
produced is caused by the reaction of
salicylic acid with aqueous ferric
ion. The oxygen atoms of Figure 7 Preparation of Methyl salicylate
the carboxylic acid group and
hydroxyl group on salicylic acid Methyl salicylate is obtained
can form a complex group with ferric from winter green oil, an aromatic
ion. It indicates the liquid distilled from the leaves of the
wintergreen plant (Gaultheria
presence of salicylic acid. In aspirin,
procumbens) or from the bark of
the hydroxyl group was replaced
sweet birch trees (Betula lenta). It has
by ester during
two main functional groups, the ester
esterification and nucleophilic
group and phenol group. Like,
substitution which prevents the
acetylsalicylic acid, methyl salicylate
complex formation. This will emanate
acid is prepared through the process
a yellow solution. However, the
of esterification. Methyl alcohol reacts
synthesized aspirin reacted in ferric
with salicylic acid in the presence of
chloride which implies that salicylic
an acid catalyst to form methyl
acid is present, as presented in Table
salicylate and a by-product of water.
2. Thus, there are impurities in the
This reaction occurs at a low
obtain aspirin.
temperature. In this experiment,
methyl alcohol was used to dissolve
Table 3. Starch Test
salicylic acid. It was subjected to
Test Tube Observation
water bath for it to produce an odor.
Commercial (+) Blue-black
The presence of methyl salicylic acid
aspirin colored solution
was confirmed in the mixture when it
Synthesized (–) No reaction produced a mint-like odor.
aspirin
Control (–) No reaction Methyl salicylate and
acetylsalicylic acid are derivatives of
Aspirin tablets are acetylsalicylic salicylic acid.
acid pressed together with a small
amount of inert binding material, such
as starch, methylcellulose and
microcrystalline cellulose. Commercial
aspirin reacted to iodine. Formation of
blue-black colored solution indicates a
positive result. In the synthesized
aspirin, there was no reaction
occurred. The control did not reacted
in iodine. This infers that there is no
starch present in the synthesized
aspirin and control which is water.
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ETHER). (n.d.). Retrieved
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http://chemicalland21.com/pe
trochemical/ACETIC
%20ANHYDRIDE.ht