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Esterification Reaction: Preparation of aspirin Report Analysis

Technical Report · September 2022

DOI: 10.13140/RG.2.2.27577.03681

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Esterification Reaction:
Preparation of aspirin
Report Analysis
 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

Title: ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

Introduction: Aspirin is the single most manufactured drug in the world. It is the
most widely sold and used over-the-counter drug. Sometimes, it is referred to as
Empirin, Bayer or St. Joseph.
It is one of a series of salicylic acid esters that has been cognized since ancientness
to have curative effects. The use of aspirin had its origin in the 18th century, when
it was found that an extract from the bark of willow trees was useful in reducing
pain and fever. The active ingredient in willow barks was later established to be
salicylic acid. Due to the unpleasant irritating side effects of the salicylic acid, in
1899, the Bayer Company in Germany manifested a drug they called aspirin, a
modification of the salicylic acid, which has the chemical name and generic form
as acetylsalicylic acid (ASA).
Aspirin is used as an analgesic drug (to relieve pain), as an antipyretic drug (to
reduce fever) and as an anti-inflammatory drug (to decrease inflammation and
swelling).
In addition to the three main uses, aspirin has been found also to have other uses
which are beneficial. These are; at low daily doses, it can lessen the chance of heart
attack in a patient with a certain heart problem and it`s dosage appears to reduce
the occurrence of stroke in some men.
Nevertheless, due to the acidic nature of the compound, aspirin has been found to
cause irritation of the stomach or ulcers in many people. As a result of this, many
people take a buffered form of aspirin to neutralize the acid as the tablet dissolves.
This entails using buffering agents; like antiacids, in the form of magnesium
hydroxide, magnesium carbonate and aluminum glycinate when mixed with the
aspirin (Buffering). Aspirin is also not advised as a medication within two weeks
of surgery, childbirth or dental extractions as it may cause serious bleeding
problems.
In this experiment, aspirin was prepared by the reaction of 2g salicylic acid with an
excess 3mL acetic anhydride. A small amount of exactly 1 drop of concentrated
sulfuric acid was used as a catalyst which sped up the reaction. The excess acetic
acid was quenched by the addition of water, which was also used to precipitate the
aspirin.

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 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

The aspirin obtained from this process was referred to as “crude product”. The
reaction for the synthesis of aspirin was as shown in the equation below:
C4H6O3 + C7H6O3 H2SO4 C9H8O4 + HC2H3O2
(Acetic Anhydride) (Salicylic acid) (Aspirin) (Acetic Acid)

This can be expanded to the following structures:

Objective: To prepare aspirin from salicylic acid by acetylation.

Apparatus Used: A 50 mL beaker, a glass rod, a bain-marie heater, vacuum
filtration, an electronic weigh balance, 3 test tubes, tit-pipette dropper, a
thermometer, Buchner funnel filter paper,
Chemical Reagents Used: 2g salicylic acid, 3mL acetic acid, 1 drop concentrated
sulfuric acid, 6 mL methanol
Procedure:
2g of salicylic acid was precisely weighed in a beaker using an electric weigh
balance and put into a 50mL beaker. 3mL of acetic acid were measured in a small
graduated cylinder and added into the 50mL beaker containing the 2g salicylic
acid.
Exactly 1 drop of concentrated sulfuric acid was at that point added to the
substances in the 50mL beaker through utilizing the tit-pipette dropper and the
mixture stirred vigorously using a glass rod. The contents in the glass beaker were
then heated by use of a bain-marie for 15 minutes till reaching 500C – 600C, while
been stirred continually with the glass rod.
These temperatures were confirmed to be so by dipping a thermometer into the
heated mixture in the beaker. 35 mL of water were thereupon added into the
mixture and the solution swirled. This mixture was put on a Buchner funnel, filter
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 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

paper and carried to the vacuum filtration pump for a filtration, which resulted to
the obtention of the “crude product”.
The amount of the crude product of aspirin obtained was thence weighed on the
electronic weigh balance and the mass recorded as M1. The crude acetylsalicylic
acid (aspirin) was on that occasion purified by recrystallization.
This implied dissolving the crude product in a hot solvent, which was 6mL of
methanol and the resulting solution poured into 20mL of hot water. Since
precipitation occurred, the mixture was heated until complete dissolution and soon
after allowed to cool down slowly (in air and in water).
After recrystallization, the solid was filtered and then dried by rubbing it between
filter papers. Using an electronic weigh balance, the mass of the pure product of
aspirin obtained was determined and recorded as M2.

Results and Observations:

The observations made were as follows:
~the contents on the beaker fully dissolved on heating after about 1 minute with
production of a pungent smell. With time, these fumes solidified on the walls of
the beaker. On addition of the water, the solidified fumes on the walls slightly
dissolves and the sticky substance doesn`t dissolve. After vacuum filtration the
filtrate was found to be slightly lower than the crude filtrate obtained at first:
M1>M2.
The following tabulated results were obtained on weighing the filtrates:

Mass of the crude product (aspirin) obtained [M1] 0.894g

Mass of the pure product (aspirin) obtained [M2] 0.345g

Discussion: Aspirin is synthesized by the reaction of salicylic acid and acetic

anhydride with production of acetic acid as the by-product.
During this reaction, a small amount of a strong acid is used as a catalyst which
speeds up the reaction: (though it`s not being a reactant nor a product in the overall
reaction).
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 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

This salicylic acid used, whose name comes from Salix, the willow family of
plants, was derived from willow bark extracts. In traditional medicine, willow bark
teas were used as headache remedies (cephalgia redresses) and other tonics, since
they contained salicylic acid which had those analgesic properties.
However, salicylic acid was found to be more acidic since it caused irritation of the
lining of the mouth, esophagus and stomach, and can cause hemorrhaging of the
stomach lining. The irritation of the salicylic acid was because it contained the
phenol group which are known to be irritating. The Bayer Company replaced the
phenol group with an ester group. This esterified compound (acetylsalicylic acid,
also called aspirin) was seen and found to be much less irritating than salicylic
acid. Unfortunately, aspirin is still irritating to the stomach and causing
hemorrhaging of the stomach walls.
In this experiment, 2g salicylic acid were reacted with excess 3mL acetic
anhydride to produce aspirin (acetylsalicylic acid) and acetic acid in the presence
of an acid catalyst, which was 1 drop of concentrated sulfuric acid.
This was an esterification reaction since an alcohol reacts with acyl chlorides or
acid anhydrides to give esters. Considering that these reactions are both
irreversible and slow, the catalyst helped to speed up this reaction.
The advantage of using acetic anhydride is that you do not produce water which
can be used for hydrolysis of the newly formed ester. Acetic anhydride is also the
most preferred acid derivative to synthesize aspirin commercially because the
acetic acid produced in this reaction can be used again, by converting it back into
acetic anhydride.
Concentrated sulfuric acid added was also used to keep everything in the acidified
protonated state.
During this experiment, the salicylic acid was the limiting reactant and the acetic
anhydride was in excess. After the heating of the mixture by the means of the bain-
marie was over, the water added reacted with acetic anhydride to form two moles
of acetic acid. This resulted to the weight of the crude product of aspirin being
higher. This reaction is as shown in the reaction below:
When the esterification reaction was over, water was added to the mixture during
the recrystallization process. Because the aspirin product is not very soluble in

4.
 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

water, this caused the precipitation of the acetylsalicylic acid and the reaction with
any remaining acetic anhydride. Since acetic acid is very soluble in water, it is
easily separated from the aspirin product through filtration.
The weight of the pure product reduced as compared with that of the crude product
because of the separation of the acetylsalicylic acid from the byproducts through
filtration.
Due to the production of the pungent fumes, and the fact that acetic anhydride is
irritating to the nose and sinuses, it`s advisable to have this practical done in a
fume chamber to avoid breathing the vapors.
Conclusion: Having done the experiment, pure product of aspirin was obtained
which measured up to 0.345g. Further tests were done to ensure the purity of the
aspirin.
Reference:
1. William H. Brown| Brent L. Iverson| Eric V. Ansyln| Christopher S. Foote, (2014), Organic
Chemistry 7th Edition, Mary Finch, United States of America, page 674.

2. Leroy G. Wade Jr, (2013), Organic Chemistry 8th Edition, GEX Publishing Services, United
States, page 802.

3. https://www.bellevuecollege.edu/wp-
content/uploads/sites/140/2014/06/161Lab_AspirinSynthesisupdatedPSGF3-27-2016.pdf

4. https://www.lahc.edu/classes/chemistry/arias/exp 5 - aspirinf11.pdf

5. https://www.csun.edu/~alchemy/Chem51-LACC/Labs/C51F07L12.pdf

5.
 ESTERIFICATION REACTION: PREPARATION OF ASPIRIN

6. https://laney.edu/cheli-fossum/wp-content/uploads/sites/210/2012/01/8-Synthesis-of-Aspirin.pdf

7. https://www.nitjsr.ac.in/course_assignment/CH31CH-33053. Aspirin Synthesis.pdf

8. https://home.miracosta.edu/dlr/pdf/102exp7.pdf

6.

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