Esters are prepared by reacting alcohols (or phenols) with carboxylic acids or their derivatives. The reaction of an alcohol with a carboxylic acid, however, is often very slow, and an unfavorable state of equilibrium between reactants and products is often observed. Esters are generally produced quickly and in high yields by reacting alcohols with acid chlorides or acid anhydrides, which are very reactive derivatives of carboxylic acids. In this laboratory you will produce an ester by reacting the alcohol with an acid anhydride. The general reaction is as follows:
R
O
O
O
R
+
H O R
1
R
O
O R
1
+ R
O
OH
Anhydride Alcohol Ester Acid
Aspirin is an ester formed by the reaction of acetic anhydride and salicylic acid. The aspirin will be prepared as follows:
O
OH
O OH
H
3
C
O
O
O
CH
3
+
OH
O
O
CH
3 +
H
3
C
O
OH
Acetic
Anhydride
Salicylic
Acid
Acetylsalicylic Acid
(Aspirin)
Acetic
Acid
Salicylic acid, used as a keratolytic agent in veterinary medicine, has no analgesic value.
When salicylic acid is esterified with acetic acid to form acetylsalicylic acid the product is a valuable pain reliever. Aspirin, since it is an ester, is capable of decomposing to form salicylic acid and acetic acid. The familiar smell of acetic acid in an aspirin bottle suggests that some of the aspirin has decomposed and has lost its effectiveness. In this laboratory you will test the aspirin you produce with an iron(III) chloride reagent for the presence of salicylic acid. This test will give an indication of whether the salicylic acid has been esterified completely. You will also test a sample of your aspirin that has been heated to accelerate decomposition. A positive test for salicylic acid suggests that decomposition has occurred.
1.
Place 250 mg of salicylic acid in a 3 (or 5) mL conical vial equipped with a stirring vane.
Now add two drops of 85% phosphoric acid and 600 µL of acetic anhydride. Mix the reactants and heat for 5 minutes using an aluminum block.
2.
Add 400 µL of water to decompose the excess acetic anhydride. Use caution since this is an exothermic reaction.
CHM 230, Preparation of Acetylsalicylic Acid, Page 1

3.
After this reaction is over, add 600 µL of water and allow the tube to cool to room temperature. To complete the crystallization, cool the tube in ice for an additional 10 minutes. Crystallization may be initiated by introducing a small crystal of aspirin to the reaction mixture, which acts as a "seed" crystal. If no aspirin crystals are available, crystallization can sometimes be initiated by scratching the side of the vial with a glass stirring rod.
4.
Collect the product on a pre-weighed filter paper in a Buchner or Hirsch funnel (see Figure
1). Wash out the conical vial with an additional small quantity of ice cold water to remove the remaining aspirin. Allow the product to dry for one week before weighing.
1.
Place several crystals of your damp aspirin in a small test tube and heat gently over a Bunsen burner. This will cause hydrolysis (decomposition). Carefully note any odor coming from the tube. Set the tube aside and save it for further testing.
2.
To each of four small test tubes add one milliliter of ethyl alcohol and one drop of 1 % FeCI
3
.
- To test tube 1, add several crystals of salicylic acid.
- To test tube 2, add several crystals of your aspirin.
- To test tube 3, add the product from heating the damp aspirin.
- Use test tube 4 as a blank.
3.
Shake each tube. Make note of any color that develops. In the presence of phenols, AROH
(such as salicylic acid), a pink-purple color develops.
Figure 1 - Vacuum Filtration with a Hirsch Funnel
CHM 230, Preparation of Acetylsalicylic Acid, Page 2

Name ____________________________________
Write a balanced equation for the preparation of aspirin:
Amount (in mg) of salicylic acid used:
Millimoles of salicylic acid used:
µL of acetic anhydride used:
Density of acetic anhydride:
Function of the phosphoric acid:
Mass of dry aspirin and filter paper:
Mass of dry aspirin and filter paper:
Mass of pre-weighed filter paper:
Experimental yield (in mg) of aspirin:
Theoretical yield (in mg) of aspirin:
% yield
Describe results of heating moist aspirin:
CHM 230, Preparation of Acetylsalicylic Acid, Page 3

Give an equation to show what occurred when the aspirin was heated:
Describe the results of the FeCl3 test in each of the test tubes
Tube Observation
Salicylic acid
Damp aspirin
Heated aspirin
Blank
Esters
1.
Give an equation for the preparation of the ester known as Oil of Wintergreen:
2.
What compounds would you expect to find present upon the decomposition of Oil of
Wintergreen?
3.
Methyl butyrate has an odor associated with apples. Give an equation to show what happens to it upon hydrolysis. Would the odor improve or get worse? Why?
CHM 230, Preparation of Acetylsalicylic Acid, Page 4