SYNTHESIS OF ASPIRIN

De Gucena C., Deparine, N., Dimayuga, M., Gabinete, A., Garcia, J., Gomez, L.
2A-PH, Faculty of Pharmacy, University of Santo Tomas

ABSTRACT
Acetylsalicylic acid is a drug formulated by the Bayer Company; since then, it has been called as aspirin
and is the most widely used medication in the world. Aspirin, a derivative of salicylic acid, is best known
for its use as a key ingredient in topical anti-acne product. Aspirin can be prepared by the esterification of
the phenolic hydroxyl group of salicylic acid with the acetyl group from acetic anhydride or acetyl
chloride. Ferric chloride test differentiates the salicylic acid from benzoic acid and its derivatives and the
starch test verifies the purity of the synthesized aspirin. Both the salicylic acid and the commercialized
aspirin produced a positive result toward the FeCl 3 while only the commercialized aspirin changed in
color proof of the presence of starch in the tablets of aspirin.

I.

INTRODUCTION

II.

Salicylic
acid,
a
monohydroxybenzoic acid, is a
colorless crystalline organic acid
widely used in organic synthesis. It
is an active metabolite of aspirin. It
is poorly soluble in water. Salicylic
acid and its derivatives are the most
widely known drugs used to reduce
pain and fever. The best known
salicylic acid derivative is salicin.
Aspirin was first produced 110 years
ago but the natural form, salicylic
acid found in plants like willow and
myrtle, has been used for thousands
of years [1]. In 1899, the Bayer
Company formulated a new drug,
acetylsalicylic acid. It was called
first acetyl-spiric-acid and then
aspirin [2].

III.

The basic conditions in the small

intestine break down aspirin into
salicylic acid which is then absorbed
into the bloodstream. Aspirin tablets
consist of acetylsalicylic acid and a
binder that keeps the tablet from
breaking up [3]. Acetylsalicylic acid
belongs to the group of medications
called analgesics which relieve pain,
antipyretics which reduce fever,

anti-inflammatories which lessen

inflammation,
and
platelet
aggregation inhibitors which are
anticlotting agents.
IV.

The objective of the experiment is to

explore the chemical process in the
synthesis of aspirin. At the end of
the synthesis, mass of the
synthesized aspirin, mass of the
filtered aspirin, volume of the acetic
anhydride used, and etc. are
expected to be measured. Another
aim of the experiment is to calculate
for the percentage yield of the
aspirin.

V.
VI.

MATERIALS AND METHODS

VII.

Three different and separate

procedures were done for the
experiment. For the reaction of
acetic anhydride and salicylic acid,
the
materials
needed
were
Erlenmeyer
flasks,
serological
pipette, Pasteur pipette, filter paper,
evaporating dish and cold distilled
water for the ice bath. After
weighing 1 gram of salicylic acid, it
was combined with 5 mL of acetic

anhydride
in
an
Erlenmeyer
flask.
5
drops
of

concentrated H2SO4 was added with

caution. The mixture was stirred
using a long stirring rod until the
salicylic acid completely dissolved.
It was then placed in an ice bath. To
synthesize the aspirin, the mixture
was filtered and the residue was
used as the synthesized aspirin for
the differentiating tests.
For the ferric chloride test, six test
tubes were prepared. The first test
tube contained pinch amount of
salicylic acid, triturated commercial
aspirin (Aspilet is the brand of the
aspirin used) on the second,
synthesized aspirin on the third,
benzoic acid on the fourth, and 5
drops of benzyl alcohol on the fifth.
The sixth test tube acted as the
control, containing only distilled
Figure 1.
water. Samples
Formation of
in powder form
intense violet
were dissolved
color
first in 1 mL of
distilled water and then 5 drops of
2% aqueous FeCl3 was introduced. A
change to violet in color was noted
for some of the samples.

X.
XI.

DISCUSSION
XII.

VIII.

IX.

For the starch test, the synthesized

aspirin
and
powdered
commercialized aspirin were put
into two separate test tubes. Only
distilled water was put in the third
test tube as a control. To each test
tube, 3 drops of potassium iodide
solution was added. The change in
colors after the addition of KI was
noted.
Figure 2.
Verification of
presence of
starch

RESULTS
AND

Aspirin is produced in a one-step

chemical process by reacting
salicylic acid with acetic anhydride
forming acetylsalicylic acid and
acetic acid. In the chemical reaction
(see Fig. 1), salicylic acid, a
carboxylic acid derivative, is
converted to another carboxylic
derivative by a process known as
nucleophilic
acyl
substitution.
Nucleophilic
acyl
substitution
implies that a nucleophile is an
electron rich species that will react
with an electron poor species, an
acyl group is R-C=O, and the
substitution note that the leaving
group
is
replaced
by
the
nucleophile. Formation of the new s
bond to the nucleophile and
breakage of the s bond to the
leaving group happen in the said
substitution reaction. Acid chlorides
react the most toward nucleophilic
acyl substitution, followed by
anhydrides, esters, then, amides[4].

XIII.

XIV.

Figure 3. Acyl Substitution of Salicylic

Acid (Source: Google Images)

XV.

The purity of the synthesized aspirin

is can be tested by the addition of
Fe3+ to as suspension of the product.

Only the salicylic acid and the

commercialized aspirin produced an
intense violet color among the four
other samples (see Tab. 1). The
color is caused by the reaction of
salicylic acid with aqueous ferric
ion. Most d-transition ions act as
Lewis acids by forming coordinate
covalent bonds with Lewis bases.
The color of complex depends on
which metals and ligands are
present.
XVI.

Test tube

XVIII. Salicylic acid

XX.

Commercial
aspirin

XXII. Synthesized
aspirin
XXIV. Benzoic acid

XXVI. Benzyl
alcohol
XXVIII.
XXX.

Control

XVII. Observations
XIX.

Intense violet
solution with
white ppt
XXI. Violet
to
black
solution with
canary
yellow ppt
XXIII. Light yellow
solution with
white ppt
XXV. Old
rose
solution with
white ppt
XXVII. Yellow
solution with
oily layer
XXIX. Clear yellow
solution

pharmaceutical companies add

starch in preparation of aspirin to
help maintain the shape of the
tablet. Since the synthesized aspirin
did not change in color, it is pure
(see Tab. 2).
XXXII. Test tube
XXXIV.
Commerci
al aspirin
XXXVI. Synthesize
d aspirin
XXXVIII. Control
XL.
XLI.

REFERENCES
[1]

XLII.

History of Aspirin. Retrieved

November
3,
2014
from
http://www.aspree.org/AUS/aspreecontent/aspirin/history-aspirin.aspx

XLIII.

[2]

XLIV.

[3]

XLV.

[4]

XLVI.

[5]

Table 1. Ferric Chloride Test

XXXI. Starch test determines whether

starch is present in the sample being
testes with the use of iodine. Iodine
is an element that turns dark blue or
black when it is mixed with starch
[5]
. Among the synthesized aspirin,
commercial aspirin, and control,
only the commercial aspirin turned
from yellow solution to black
solution. This holds the truth that

XXXIII.
Observatio
ns
XXXV. Yellow
solution
to
black solution
XXXVII. No change
in color
XXXIX. Clear
solution

XLVII.

Hayat, S., Ahmad, A., &

Alyemeni, M. (2013). Salicylic
Acid:
Plant
Growth
and
Development.
Heidelberg,
Germany: Springer Science &
Business Media
Ault, A. (1998). Techniques and
Experiments for Organic Chemistry.
(1998). California, United States of
America: University Science Books
Macomber, R. (1996). Organic
Chemistry vol. 2. (1996). California,
United
States
of
America:
University Science Books
Carter, P., Badenhorst, C.,
Damerell, C., Dawson, C., &
Centaur-Harris, O. (2006). Natural
Sciences Grade 8. Claremont, South
Africa: New Africa Books