Preparation of Aspirin

When an organic acid, R-COOH, is heated with an alcohol, R’-OH, in the

presence of a strong acid, the chief organic product is an ester.

The general reaction for the esterfication of an organic acid with an alcohol is:

R-COOH + R’-OH → R-CO-OR’ + H2O

For example, if acetic acid is heated with ethyl alcohol, the esterfication would be:

CH3-COOH + HO-CH2CH3 → CH3-COO-CH2CH3 + H2O

The ester product would be named ethyl acetate.

One common ester is acetylsalicylic acid, commonly known as aspirin. Since

ancient times it has been known that the barks of certain trees had pain- killing and fever-
reducing properties. The active ingredient of the bark was determined to be salicylic
acid. Pure salicylic acid cannot be used medicinally because it is extremely harsh on the
digestive tract. In the late 1800’s, the German company Bayer patented an ester
derivative of salicylic acid that is much less harsh but has the desired pain-killing, and
fever-reducing properties. The word equation for the synthesis of aspirin is:

Salicylic acid + acetic anhydride → acetylsalicylic acid (aspirin) + acetic acid

Procedure

• Half fill a 400 mL beaker with water and warm it on a hot plate to ~70o C.
• Add 1.5 g of salicylic acid (record the exact amount) to a 125 mL Erlenmeyer
flask.
• In the exhaust hood, add approximately 4 mL (record the exact volume)of acetic
anhydride and 3-4 drops of 50% sulfuric acid. Stir until the mixture is
homogenous.
• Transfer the Erlenmeyer to the 70o C water under the ventilations system and heat
for 15-20 minutes stirring occasionally. Monitor the temperature – do not let the
temperature rise above 70o C.
• At the end of the heating period, cool the Erlenmeyer in and ice bath until crystals
begin to form. If the crystallization does not take place, scratch the walls and
bottom of the flask to promote crystal formation.
• To destroy any excess acetic anhydride, add 50 mL of cold water, stir, and allow
the mixture to stand for at least 15 minutes.
• Use a Buchner funnel to filter the crystals. Wash the crystals with two 10-mL
protions of cold water to remove and excess reagent. Record the mass of aspirin
produced.

(This is a crude product of aspirin. A purified sample could be extracted with

more filtration and ethyl alcohol.)

Tests on Aspirin

1. Test with bicarbonate

Acetylsalicylic acid molecules still contain an organic acid group and will react
with sodium bicarbonate to release carbon dioxide gas

H+ + HCO3- → CO2 + H2O

Add a small portion of your aspirin to a test tube. Also add a portion of sodium
bicarbonate. Add a small amount of water and observe. The evolution of carbon
dioxide indicates that aspirin is an acid – but is not a specific test for aspirin.

2. Test with Iron(III)

If the synthesis of aspirin has not been effective, then free salicylic acid will be
present. This would be harmful if ingested. The standard test for salicylic acid is
to treat the sample with a solution of iron(III).If salicylic acid is present, the –OH
group will produce a purple color with iron(III) ions. The intensity of the color is
directly proportional to the amount of salicylic acid.
 Set up three test tubes in a rack. To the first add a small quantity of pure salicylic
acid as a control. To the second test tube add a small portion of your crude
aspirin. To the third test tube add a small sample of pure aspirin.

Add 5 mL of water to each test tube and stir to mix. Add 8-10 drops if iron(III)
chloride solution. Note the appearance and intensity of a pink / purple color.

For the report

Introduction
Write the purpose of the lab. Include definitions of esters, alcohols and organic acids.
Include the formula equation for the reaction, and use ChemId to look up the structures
and Chemsketch to show the structural formulas for the reaction.

Material and methods

Include a reagents table for salicylic acid, acetic anhydride and sulfuric acid. The table
should include the formula, molar mass, density, melting point and boiling point. You
will need to do some Internet research to find these properties.

Results
Record the mass of aspirin produced

Include observations about the synthesis and observations from the tests with bicarbonate
and iron(III).

Include a products table for aspirin and acetic acid. The table should include the formula,
molar mass, density, melting point and boiling point.

Discussion
Discuss the purity of your sample based on the iron (III) test.

Based on the balanced chemical equation, the mass of acetic salicylic acid, the volume
and density of acetic anhydride calculate a theoretical mass of aspirin that should be
produced. Calculate a Percent Yield for the reaction? Show calculations

Calculate the ∆H of the reaction using average bond energies from the text. Show work /
explain your calculations.

Using the structural formulas from the intro, determine the molecular geometry and
hybridization for each of the central atoms in aspirin.