BioOrg.Chem. By Alaa.J.Mahrath
BPreparation
alajm68@uobabylon.edu.iq
of acetylsalicylic acid (aspirin)
Background:
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
anti-inflammatory 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:
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
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 acetic
anhydride and an acid catalyst, like sulfuric or phosphoric acid, to
speed up the reaction with salicylic 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.
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
rocedure
Preparation of Aspirin:
1. Prepare a bath using a 400-mL beaker filled about half way with
water. Heat to boiling.
2. Take 2.0 g of salicylic acid and place it in a 125-mL Erlenmeyer
flask. Use this quantity of salicylic acid to calculate the
theoretical or expected yield of aspirin . Carefully add 3 mL of
acetic anhydride to the flask and, while swirling, add 3 drops of
concentrated phosphoric acid.
CAUTION!
Acetic anhydride will irritate your eyes. Phosphoric acid will cause burns to the
skin. Use gloves with these reagents. Handle both chemicals with care. Dispense
in the hood.
3. Mix the reagents and then place the flask in the boiling water
bath; heat for 15 min. (Fig. 1). The solid will completely dissolve.
Swirl the solution occasionally.
4. Remove the flask from the bath and let it cool to approximately
room temperature. Then, slowly pour the solution into a
150-mL beaker containing 20 mL of ice water, mix thoroughly,
and place the beaker in an ice bath. The water destroys any
unreacted acetic anhydride and will cause the insoluble aspirin
to precipitate from solution.
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
5. Collect the crystals by filtering under suction with a Büchner
funnel. The assembly is shown in Fig. 1
6. The Büchner funnel is inserted into the filter flask through either a
filtervac, . Filter paper is then placed into the Büchner funnel. Be
sure that the paper lies flat and covers all the holes.
7. Wash the crystals with two 5-mL portions of cold water, followed
by one 10-mL portion of cold ethanol.
8. Using a spatula, place the crystals between several sheets of
paper toweling or filter paper and press dry the solid.
9. Weigh the filter paper with crystals. Calculate the weight of crude
aspirin . Determine the percent 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 X 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.
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
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.
Chemicals and Equipment
1.
Acetic anhydride
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Concentrated phosphoric acid, H3PO4
Commercial aspirin tablets
95% Ethanol
1% Iron(III) chloride
Salicylic acid
Boiling chips
Büchner funnel, small
250-mL filter flask
Filter paper
Filtervac or neoprene adapter
Hot plate
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
PRE-LAB QUESTIONS:
v List four medicinal applications for aspirin.
v Draw the structure of aspirin. Should this compound test
positive with 1% iron(III) chloride solution? Explain your
answer.
v Aspirin can irritate the stomach. What functional group in
the molecule is responsible for this effect?
v How do the buffering agents that are added to aspirin
tablets relieve the irritating side effects?
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
NAME
SECTION
PARTNER
GRADE
DATE
REPORT SHEET
1. Theoretical weight :
180 g aspirin
1 mole
_____________g salicylic acid X --------- X -----------1 mole
138 g salicylic acid
=-------------g
Percentage Yield of Aspirin = (Exp. Wt / Thero. Wt ) × 100%
aspirin
2. Weight of 50-mL beaker
_________ g
3. Weight of your aspirin and beaker.
_________ g
4. Weight of your aspirin: (3) — (2)
_________ g
5. Percent yield: [(4)/(1)] X 100 = %
_________ %
6. Iron(III) chloride test.
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
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?
BioOrg.Chem. By Alaa.J.Mahrath
alajm68@uobabylon.edu.iq
AJM .BioorgChem.