Exercise No.

11

SYNTHESIS OF ASPIRIN

(Acetylsalicylic acid from salicylic acid)

Jennie Marie. E. Orbiso

Group Number II

CHEM 40.1 – 7L
 I. Introduction

Synthesizing an organic compound is an important knowledge or tool in the organic

industry. Organic synthesis is a means of describing the preparation of a desired organic
compound from materials that are readily available in the laboratory by the modification of
molecules of another organic compound which is called the starting material (Lehman, 2009).
Its main goal is to obtain a pure sample of the product by conducting the simplest, yet most
efficient, steps possible.

One of the most widely used analgesics (pain-relieving drugs) in the market today is
acetylsalicylic acid, popularly known as Aspirin. As an antipyretic, it lowers the body
temperature when one has fever. It also acts as an anti-inflammatory agent thus, reduces pain
(Bailey, 1985).

When taken into the stomach, aspirin is hydrolyzed back to salicylic acid (Laboratory Manual
for a course in Basic Organic Chemistry, 2004). Salicylic acid is used as a disinfectant and is
effective as an antipyretic. However, it causes stomach distress in some users (Bailey, 1985). It
is in the form of white crystalline powder and has a melting point range of 134 - 136˚C (Sigma-
Aldrich, 2014). Aspirin is synthesized when salicylic acid (C7H6O3) reacts with acetic anhydride
(C4H6O3). Phosphoric acid (H3PO4) is added to the solution to act as a catalyst to initiate the
reaction.
 This synthesis of aspirin undergoes a complex mechanism and involves a nucleophilic acyl
substitution.

The beneficial effects of aspirin include its ability to improve blood clotting processes.
According to some studies, continuous, small doses intake of aspirin can help lower the risk of
heart attack (Bailey, 1985). Also, it stops the production of prostaglandins which trigger pain,
fever, and inflammation in the body (Laboratory Manual for a course in Basic Organic
Chemistry, 2004).

II. Objectives

This exercise aims to explain the concept of organic synthesis; synthesize acetylsalicylic acid
(aspirin) from salicylic acid by nucleophilic acyl substitution, and; describe and explain
differences in the properties of aspirin and salicylic acid through simple chemical steps.
III. Materials and Methods
A. Schematic diagram for synthesis and recrystallization of aspirin

1 g of salicylic acid in 125 mL

Erlenmeyer flask

+ 3 mL acetic anhydride
+ 5 drops of 85% phosphoric acid
Swirl to mix

Heat in steam bath for 15 minutes

+ 2 mL dH2O
+ 20 mL ice-cold water
Cool to room temperature

Place in ice bath to complete

crystallization

Collect product through suction filtration

Wash several times with cold water

Crude aspirin

Small quantity

Determine melting point Transfer to 125 mL Erlenmeyer flask

+95% ethanol

+cold water

Place in cool bath

(Cont. of schematic diagram)

Place in cool bath

(Appearance of crystals)

Collect by suction filtration

Wash crystals several times with small

portions of cold water

Transfer to pre-weighed watch glass

Recrystallized aspirin

Determine melting point

B. Setups to be used

(http://www.chem.latech.edu/~deddy/chem104/104Aspirin.htm)

Figure 1.1. Suction filtration setup.

(http://www.oocities.org/capecanaveral/Hall/1410/lab-C-14.html)

Figure 1.2. Melting point determination setup.

 C. Necessary Chemicals

Name and Function in Physical Hazards Precautions

Structure Exercise Properties
Salicylic Acid For deriving MM=138.12 g/mol Mildly irritating Use face mask
(C7H6O3) acetylsalicylic BP = 211˚C Causes skin and gloves
acid MP = 159˚C irritation If skin contact
Density = 1.44g/cm3 occurs,
White crystalline immediately
powder wash with soap
and water
Acetic Anhydride To react with MM=102.05 g/mol Corrosive Wear proper
(C4H6O3) salicylic acid BP = 141.1˚C Causes skin protective
to form MP = 159˚C irritation and equipment
acetylsalicylic Density = 1.1g/cm3 possible burns Keep away from
acid Colorless liquid flame or heat
Phosphoric acid Act as MM=98.02 g/mol Irritating to the Wear proper
(H3PO4) catalyst BP = 407˚C eyes and nose protective
MP = 42.4˚C Dries skin equipment
Density = 1.9g/cm3
Colorless liquid or
crystals
Ethanol To dissolve MM=46.05 g/mol Extremely Keep away from
(C2H6O) aspirin BP = 780˚C flammable sparks, heat, and
MP = 1150˚C Irritating to the open flames
Density = 1.9g/cm3 eyes and skin Wear proper
Colorless liquid protective
equipment
Ferric Chloride To MM=162.2 g/mol Irritating Avoid inhalation
(FeCl3) differentiate BP = 315˚C especially if there Wear proper
synthesized MP = 306˚C is contact protective
from Density = 2.9g/cm3 equipment
commercial Rusty-borwn liquid
aspirin
Iodine (I) To Irritating Avoid inhalation
differentiate Wear proper
synthesized protective
from equipment
commercial
aspirin
Potassium To MM=158.03 g/mol Damaging if Keep away from
Permangate differentiate MP = 240˚C contact occurs sparks, open
(KMnO4) synthesized Density = 2.7g/cm3 flames, and heat
from Pinkish liquid Wear proper
commercial protective
aspirin equipment
 IV. Data

Table 1.1. Appearances of different compounds and chemicals used.

Compound Observations
Salicylic acid White crystalline powder
Acetic anhydride Colorless liquid
Phosphoric acid Colorless liquid
Ethanol Colorless liquid
Ferric chloride Rusty brown liquid
Iodine
Potassium permanganate Pinkish liquid

Table 1.2. Yield in the preparation of aspirin.

Mass (g)
Salicylic acid 1.00
Watch glass 42.50
Synthesized aspirin + watch glass 49.90
Crude Aspirin 7.40
Percent Yield: 469.23%

Table 1.3. Recovery in the recrystallization of aspirin and its melting points.

Mass (g) Melting Points (˚C)

Crude Aspirin 7.40
Watch glass 42.50 N/A
Watch glass + recrystallized 49.90
aspirin
Recrystallized aspirin 7.40
Melting Point Difference
Percent Recovery: 100%

Table 1.4. Reactions of synthesized and commercially available aspirins.

Sample Observations Reaction Reaction Reaction Reaction

Aspirin with water with FeCl3 with I with KMnO4
Commercial White powder Insoluble - Purple + Purple +
Synthesized Soft, smooth Insoluble - Red - Cloudy -
white mixture Orange mixture
 V. Sample Calculations
𝐴𝑐𝑡𝑢𝑎𝑙 𝑦𝑖𝑒𝑙𝑑−𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑦𝑖𝑒𝑙𝑑
Percent yield = 𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙
𝑥 100

𝑚𝑜𝑙 𝑠𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝑎𝑐𝑖𝑑 𝑚𝑜𝑙 𝑝𝑟𝑜𝑑𝑢𝑐𝑡 𝑀𝑀 𝑝𝑟𝑜𝑑𝑢𝑐𝑡

Theoretical yield = (𝑔 𝑠𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝑎𝑐𝑖𝑑)( 𝑚𝑎𝑠𝑠
)(𝑚𝑜𝑙 𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡)(𝑚𝑜𝑙 𝑝𝑟𝑜𝑑𝑢𝑐𝑡)

1𝑚𝑜𝑙 𝑆𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝑎𝑐𝑖𝑑 1𝑚𝑜𝑙 𝑎𝑠𝑝𝑖𝑟𝑖𝑛 180𝑔

Theoretical yield = 1 𝑔 𝑠𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝑎𝑐𝑖𝑑 𝑥 138𝑔
𝑥 (1𝑚𝑜𝑙 𝑆𝑎𝑙𝑖𝑐𝑦𝑙𝑖𝑐 𝑎𝑐𝑖𝑑) 𝑥(1𝑚𝑜𝑙 𝑎𝑠𝑝𝑖𝑟𝑖𝑛)

Theoretical yield = 1.30 g Aspirin

𝑐𝑜𝑙𝑙𝑒𝑐𝑡𝑒𝑑 𝑚𝑎𝑠𝑠
Percent Recovery = 𝑖𝑛𝑖𝑡𝑖𝑎𝑙 𝑚𝑎𝑠𝑠
𝑥100

VI. Results and Discussion

The exercise aimed to synthesize aspirin using salicylic acid and acetic anhydride via
nucleophilic acyl substitution. A gram of salicylic acid was placed in a 125 mL Erlenmeyer flask
then 3 mL of acetic anhydride was added. Phosphoric acid (5 mL) was also added to the
solution to serve as a catalyst. This mixture was then heated in a steam bath for 15 minutes
and recrystallization completed after some time in a cold water bath. The resulting compound
(crude aspirin) was collected through suction filtration. Theoretically, the observed product
(crude aspirin) is in crystalline form however, the actual product is a smooth white mixture that
soft. It did not crystallize. Upon weighing, 7.40 g of crude aspirin was yielded from 1.00 g of
salicylic acid. This shows a 469.23% of percent yield in the experiment.

The obtained crude aspirin was subjected to another recrystallization. It was transferred to
a 125 mL Erlenmeyer flask and 95% ethanol and cold was added. The mixture was placed in a
cold water bath and the solution begins to recrystallize. The resulting product was obtained
through suction filtration. It was placed in a pre-weighed watch glass and the mass of the
product was 7.40 g. The computed total recovered aspirin was 100%. Again, the aspirin
collected were not crystals but a smooth white mixture.

The melting points of the crude and recrystallized aspirin were not measured during the
experiment.
 The possible sources of error in the experiment were: (1) the collected crude aspirin was
not dried and immediately subjected to another recrystallization; (2) the Erlenmeyer flask used
was not clean, and; (3) the solution did not heat in a steam bath for 15 minutes.

If the collected crude aspirin was weighed while it is not dry, its mass would weigh more.
Thus, the experiment cannot clearly say that it recovered 100% of the recrystallized aspirin
from the crude aspirin. Also, the percent recovery in the experiment was a large value
amounting to 469.23%. This was, however, not precise and accurate because the collected
crude aspirin was not air dried. The wet product was put in a pre-weighed watch glass so the
resulting mass is higher compared to the actual value.

The uncleansed Erlenmeyer flask would result to the addition of impurities to the solution.
This may contribute to the additional mass of the resulting product (aspirin). This may also
contribute to the reasons why the product yielded was not in the form of crystals. If the
solution was not heated properly, it may have not undergone complete dissociation and
dissolution of salicylic acid and acetic anhydride. Thus, the resulted product was in the form of
a smooth, milky white mixture.

The synthesized aspirin was compared to the commercially available aspirin via three tests.
The commercially available aspirin was crushed until it is in powdered form. Then, the solubility
in water of both aspirins was tested. Both the synthesized and commercial aspirin were
insoluble in water. Then they were reacted with aqueous FeCl3. The commercial aspirin gave a
positive result with its content being a purple solution. The synthesized aspirin showed a
negative result because its solution became red orange in color. Upon reaction with iodide
solution, the commercially available aspirin showed a positive result, having a purple solution
however, the synthesized aspirin showed another negative result, having a cloudy mixture as
the product.

From the results obtained, the commercial aspirin and the synthesized aspirin did not match
well in terms of their reactions with different compounds. This may be due to the differences in
their chemical structure which can easily be seen by the difference in their appearances. The
commercially available aspirin was in white crystalline form while the synthesized aspirin is a
smooth, milky white mixture.
 VII. Summary and Conclusion

The objectives of the exercise were met. The aspirin was synthesized however; there
are errors in the synthesis process which explains the reason for the differences between the
commercial aspirin and the synthesized aspirin. The percent yield (469.23%) from the
experiment showed an erroneous result because only 1.00 g of salicylic acid was used in the
experiment and the crude aspirin synthesized weighed a total of 7.40 g. The maximum amount
of aspirin that can be yielded was only 1.30 g. Meanwhile, the recrystallized aspirin showed a
100% recovery from the crude aspirin. Overall, the synthesized aspirin was different from the
commercial aspirin in the market.

VIII. References

Bailey, P. S. (1985). Organic Chemistry: A Brief Survey of Concepts and Applications. Massachusetts: Allyn
and Bacon, Inc.

Laboratory Manual for a course in Basic Organic Chemistry. (2004). University of the Philippines LB:
Division of Organic Chemistry and Natural Products.

Lehman, J. W. (2009). Multiscale Operational Organic Chemistry: A Problem Solving Approach to the
Laboratory Course. New Jersey: Pearson Prentice Hall.

Sigma-Aldrich. (2014). Retrieved November 22, 2014, from Sigma-Aldrich:

http://www.sigmaaldrich.com/catalog/product/sigma/a5376?lang=en&region=PH

IX. Remarks and Recommendations

The results obtained from the experiment shows that the synthesized aspirin was not the
same, in terms of its physical properties, with the commercially available aspirin. The
experiment can be further improved by strictly following the steps for the synthesis of aspirin.
The time that the solution must be kept in a hot or cold bath must be followed. Also, the
materials or glass wares that will be used must be kept clean to avoid contamination and
addition of impurity to the resulting product.