Experiment 4: Preparation of Aspirin

Requirements:
Reagents: Acetyl Chloride (CH3COCl), Pyridine, Concentrated Sulfuric Acid, commercial
Aspirin tablets, Ethanol, Salicylic Acid,
Apparatus: Buchner Funnel (small), 100 mL or 250 mL filter flask, Filter paper, Filtervac or
neoprene adapter, Hot plate, Boiling Chips

Theory:
One of the most widely used nonprescription drugs is aspirin. In the United States, more than
15,000 pounds are sold each year. It is no wonder there is such wide use when one considers
the medicinal applications for aspirin. It is an effective analgesic (pain killer) that can reduce
the mild pain of headaches, toothache, neuralgia (nerve pain), muscle pain, and joint pain
(from arthritis and rheumatism). Aspirin behaves as an antipyretic drug (it reduces fever) and
an antiinflammatory agent capable of reducing the swelling and redness associated with
inflammation. It is an effective agent in preventing strokes and heart attacks due to its ability to
act as an anticoagulant by preventing platelet aggregation.
Early studies showed the active agent that gave these properties to be salicylic acid.
However, salicylic acid contains the phenolic and the carboxylic acid groups. As a result, the
compound was too harsh to the linings of the mouth, esophagus, and stomach. Contact with the
stomach lining caused some hemorrhaging. The Bayer Company in Germany patented the ester
acetylsalicylic acid and marketed the product as aspirin in 1899. Their studies showed that this
material was less of an irritant; the acetylsalicylic acid was hydrolyzed in the small intestine to
salicylic acid, which then was absorbed into the bloodstream. The relationship between salicylic
acid and aspirin is shown in the following formulas:
COOH
OH

COOH
O
O

Salicylic Acid

Acetylsalicylic Acid
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Aspirin still has side effects. Hemorrhaging of the stomach walls can occur even with normal
dosages. These side effects can be reduced through the addition of coatings or through the use
of buffering agents. Magnesium hydroxide, magnesium carbonate, and aluminum glycinate,
when mixed into the formulation of the aspirin (e.g., Bufferin), reduce the irritation.
This experiment will acquaint you with a simple synthetic problem in the preparation of
aspirin. The preparative method uses acetyl chloride and a base (sodium carbonate).
COOH
OH

Base
Cl

Salicylic Acid

COOH
O
O

Acetyl Chloride

Acetylsalicylic Acid

If any salicylic acid remains unreacted, its presence can be detected with a 1% iron(III)
chloride solution. Salicylic acid has a phenol group in the molecule. The iron(III) chloride gives
a violet color with any molecule possessing a phenol group. Notice the aspirin no longer has the
phenol group. Thus a pure sample of aspirin will not give a purple color with 1% iron(III)
chloride solution.

Preparation of Aspirin
1. Place 1.0 g of salicylic acid in a 100 mL Erlenmeyer flask.
2. Add 2.0 mL of pyridine (just sufficient to dissolve the salicylic acid), keeping the Erlenmeyer
flask in an ice-bath. Keep the Erlenmeyer flask in the hood while doing this addition.
Use gloves so as to avoid any contact with your skin.

Fig. 1 Assembly for the synthesis of aspirin.

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3. Add 2.0 mL of acetyl chloride and 0.1 mL of concentrated H2SO4 to the solution in the
beaker. Stir the solution thoroughly using a glass rod. (Keep the mixture in the hood).
4. Add 15 mL of cold distilled water to the mixture and heat to 60 C on a hot plate to ensure
total dissolution.
5. Cool to room temperature. Place in an ice-bath until crystals begin to form.
6. Filter the mixture by obtaining a 250-mL filter flask and connect the side arm of the filter
flask to a water aspirator with heavy wall vacuum rubber tubing. (The thick walls of the
tubing will not collapse when the water is turned on and the pressure is reduced)

Fig 2. Filtering using Buchner funnel

7. The Bchner funnel is inserted into the filter flask through a filtervac or a neoprene adapter,

or a one-hole rubber stopper, whichever is available. Filter paper is then placed into the
Bchner funnel. Be sure that the paper lies flat and covers all the holes. Wet the filter paper
with water.
8. Turn on the water aspirator to maximum water flow. Pour the solution into the Bchner
funnel.
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9. Wash the crystals with cold distilled water, and dry between pieces of filter paper.
10. Transfer the crystals into a 50 mL beaker. Add 10 mL of ethanol and 10 mL of water.
11. Heat the mixture until the mixture evaporates.
12. Cool the solution to the room temperature.
13. Place this solution in an ice bath so as to induce crystallization.
14. Filter the solution. Wash the crystals with cold distilled water.
15. Dry the crystals between pieces of filter paper and weigh.

Report the yield and yield %

Yield =
Yield % =

Determine the Purity of the Aspirin

1. The aspirin you prepared is not pure enough for use as a drug and is not suitable for
ingestion. The purity of the sample will be tested with 1% iron(III) chloride solution and
compared with a commercial aspirin and salicylic acid.
2. Label three test tubes (100 13 mm) 1, 2, and 3; place a few crystals of salicylic acid into
test tube no. 1, a small sample of your aspirin into test tube no. 2, and a small sample of a
crushed commercial aspirin into test tube no. 3. Add 5 mL of distilled water to each test tube
and swirl to dissolve the crystals.
3. Add 10 drops of 1% aqueous iron(III) chloride to each test tube.
4. Compare and record your observations. The formation of a purple color indicates the
presence of salicylic acid. The intensity of the color qualitatively tells how much salicylic
acid is present.

PRE-LAB QUESTIONS
1. List four medicinal applications for aspirin.

2. Draw the structure of aspirin. Should this compound test positive with 1% iron(III)
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chloride solution? Explain your answer.

3. Aspirin can irritate the stomach. What functional group in the molecule is responsible for
this effect?

4. How do the buffering agents that are added to aspirin tablets relieve the irritating side
effects?

REPORT SHEET
Theoretical yield:
______________ g salicylic acid

180 g aspirin
1 mole

1 mole
138 g salicylic acid
______________ g aspirin

Weight of 50-mL beaker

______________ g

Weight of your aspirin and beaker

______________ g

Weight of your aspirin: (3) - (2)

______________ g

Percent yield: [(4)/(1)] 100 = %

______________ %

Iron(III) chloride test

No.

Sample

Salicylic acid

Your aspirin

Commercial
aspirin

Color

Intensity

POST-LAB QUESTIONS
1. How was the rate of the reaction increased?

2. What would happen to your percent yield if in step no. 11 of the procedure you failed to dry
completely your aspirin preparation by omitting the drying between filter paper?

3. A student expected 12.0 g of acetylsalicylic acid, but obtained only 7.5 g. What is the
percentage yield?

4. Two nonprescription pain relievers are available as substitutes for aspirin: Ibuprofen and
Naproxen. Would each of these drugs give a positive phenol test? Explain your answer.
What functional group is common to each of these drugs?

COOH
O
COOH

Ibuprofen

Naproxen