Synthesis of Acetylsalicylic Acid through Esterification

Helen Rowi M. Tolentino, Jose Angelo S. Trinidad, Maria Cherisse P. Tuazon. Maria Christine P.
Tuazon**
College of Science, Department of Biological Sciences, University of Santo Tomas, Espaa
Blvd., Manila

Abstract
The experiment seeks to synthesize and purify acetylsalicylic acid from a reaction of salicylic acid and acetic
anhydride. Recrystallization was the technique used in purifying and a Hydoxamic test was used to characterize
Aspirin. The researchers were able to obtain a 70.3313 percentage yield after the experiment.
Keywords: Acetylsalicylic Acid, Aspirin, Salicylic acid, Acetic anhydride, Recrystallization

Introduction
Acetylsalicylic acid or aspirin is one of the oldest drugs known to Medicine. It is
commonly used as an analgesic. Its history dating back since ancient Greek times. Salicylic acid
was first used as an analgesic for centuries. However, using Salicylic acid alone caused various
negative results such as gastric pains that would cause more problems rather solving the original
problem. Salicylic acid was corrosive, therefore, adding an acetyl group would help solve this
problem. The term Aspirin then was used to reflect its acetic nature and its natural occurrence in
the spirea plant.
Salicylic acid, also known as 2-Hydroxybenzoic acid, is a phenolic phytohormone. Its
chemical structure is composed of a carboxylic group with a phenol whose hydroxyl group
attached to the second carbon. Acetic, also known as ethanoic anhydride, is commonly used for
acetylations in the production of commercial products.
The synthesis of Aspirin is made possible by Esterification. Esterification is simply the
reaction between a carboxylic acid and an alcohol with the presence of an acid catalyst.
Recrystallisation is a technique used to purify an organic compound. The goal is to find a solvent
1

that dissolves the product more readily at a high temperature than at a low temperature. This
would help remove impurities obtained during the synthesis proper. A Hydroxamic test is used to
test for amides and esters by the production of hydroxamic acids.
The experiments objective is to synthesize, isolate and purify aspirin from a one-step
reaction of salicylic acid and acetic anhydride. It also aims to characterize aspirin to confirm its
molecular structure.

Methodology
In choosing the crystallizing agent, a micro-spatula of pure aspirin was placed in 3
separate test tubes. 1 ml of water, hexane, and methanol was added to the first, second and third
tube respectively. The mixtures were heated in boiling water and their solubility were recorded.
The mixtures were then placed in a beaker of ice water to cool. Their solubility was recorded as
well. Based on the observations, the best solvent was chosen.
For the synthesis of Aspirin, 2 grams salicylic acid, 4 acetic anhydride and 5 drops of
concentrated

H 2 SO 4

were mixed in an Erlenmeyer flask. The mixture was heated in a

80

C water bath. The heated flask was then cooled through a running tap. 20 ml ice water was added
to the flask and was then placed in an ice bath. A vacuum filter was then used for the aspirin
crystals.
Purification was done by transferring all the solids in a beaker and adding just enough of
the recrystallizing solvent. The solids were then boiled and let cool in an ice bath. The mixture
was then subjected to a vacuum filter again. After vacuum filtration, grain-sized aspirin crystals
2

were separated from the filtrate. The grain-sized aspirin was dissolved with ethanol and
subjected to the Hydroxamic Test. The aspirin crystals left were then transferred to a filter paper
and let dry in the locker. After several days, the filtered aspirin crystals on the pre-weighed filter
paper. And the percentage yield was calculated.

Results and Discussion

Salicylic acid
Round filter paper
Pre-weighed square filter paper
Post-weighed square filter paper
Actual yield
Theoretical yield
Percentage yield

2.0080g
0.1681g
0.9821g
2.4151g
1.4330g
2.0294g
70.61%

Table 1

2.008 g Salicylic acid .

1mol SA
1 mol Aspirin 140.146 g Aspirin
.
.
=2.0375 g Aspirin
138.118 g SA
1 mol SA
1mol Aspirin

1.4330 g
.100=70.3313
2.0375 g
Hydroxamic Test:
Sample
Standard Aspirin
Experimental Aspirin

Result
Dark Purple
Dark Purple with colorless bottom

Table 2

Salicylic acid, acetic anhydride, and an acid catalyst

2
( SO 4 )

are mixed and

heated briefly. This process is commonly known as Esterification. In the process, the hydroxyl

group from salicylic acid is cleaved from the carboxylic acid by replacing it with the ester group
from the acetic anhydride, forming acetylsalicylic acid. The hydroxyl group attached to the other
ester from acetic anhydride and forms the other product; Acetic acid. The reaction is optimized
when done at a temperature of

800 C, using a temperature higher than this could decompose

the reactants. Adding ice water aids in the solidification of the product. The solid produced after
this is the acetylsalicylic acid. The other contents that are left should be separated from the solid
that is why a vacuum filter was used. However, the solid product is not pure since there may be
some of the reactants left.

Figure 1

Adding the crystallizing solvent (water) dissolves the salicylic acid and converts the
excess anhydride to acetic acid. This purifies the product. Vacuum filtering it finally separates
the aspirin from the impurities.
Esters react with hydroxylamine with the aid of sodium hydroxide to form the sodium
salt of the corresponding hydroxamic acid. On acidification (addition of HCl) and addition of
ferric chloride, the purple-colored iron (III) complex of the hydroxamic acid is formed. That is

why the hydroxamic acid test gave a positive result. The standard aspirin and the experimental
aspirin showed similar results, confirming to have the same product present.
The actual yield was calculated by subtracting the weight of the pre-weighed square
filter paper from the weight of the post-weighed square filter paper. The theoretical yield was
calculated by dividing 2.008g of salicylic acid by the molecular weight of salicylic acid. Next
step was to multiply it with the molecular weight of acetylsalicylic acid, resulting to the
theoretical yield. The percentage yield was computed by dividing the actual yield by the
theoretical yield and multiplying it to 100.

Conclusion
Acetylsalicylic acid was successfully synthesized by reacting salicylic acid and acetic
anhydride. The researchers were able to compute a 70.3313 percentage yield. Both the standard
aspirin and experimental aspirin tested positive in the Hydroxamic acid test, confirming the
presence of esters, thus the presence of Acetylsalicylic acid.

References
Ebbing, D. & Gammon, S. (2016). General Chemistry (11th ed.). New York, NY:
Cengage Learning
Lewis, D. (2003). Aspirin. London: Royal Society of Chemistry
Mwaniki, J. (2015). Chemistry 2. University of Nairobi: Department of Chemistry

Pavia et al. (1998). Introduction to Laboratory Techniques. USA: Harcourt Brace & Company

Williamson K. et al. (2011) Macroscale and Microscale Organic Experiments.

Cengage Learning
Basic Organic Chemistry Laboratory Course. (2013). University of Helsinki: Laboratory of
Organic Chemisrty

Esterification: Preparation of Aspirin (Acetylsalicylic acid).

http://fog.ccsf.cc.ca.us/pherrman/documents/aspirin.pdf (May 12, 2016)
Esterification: The Synthesis of Aspirin (ASA)
http://www.drcarman.info/kem220lb/01lab220.pdf (May 12, 2016)