Practical problem 6: The Synthesis of Aspirin and Other Esters

OBJECTIVE
Synthesize aspirin and oil of wintergreen.
Calculate a percentage yield for your prepared aspirin.

INTRODUCTION
Esters are organic compounds that are often pleasant smelling and, in some cases, are responsible for the
flavors and fragrances of fruits and flowers. Fats, oils, and waxes are naturally occurring esters of great
biological importance. Esters can be prepared by reacting an alcohol with a carboxylic acid. However, the
process is reversible and equilibrium is reached slowly unless a catalyst, such as sulfuric acid, is used.

EXPERIMENTAL PROCEDURE
A. Synthesis of Aspirin

Salicylic acid is a carboxylic acid that, along with its derivatives, has long been used as a mild analgesic
(pain reliever) and antipyretic (fever reducer). Salicylic acid molecules contain both a phenol and a
carboxylic acid group. Therefore, it can form esters by behaving as a phenol and reacting with an acid or
by acting as an acid in a reaction with an alcohol. Aspirin (acetyl salicylic acid) is an ester in which a
reaction has taken place between the OH of the phenol of salicylic acid and the carboxyl group of acetic
acid, although it is usually prepared by using the more reactive acetic anhydride in place of acetic acid.
The preparation of aspirin is illustrated by the following reaction:

Procedure
1. Set up a hot water bath with half full of water, until it reaches a temperature of 85 to 90 0C, then remove
from the heat source
2. Use an electronic balance to accurately weigh 0.2 g of salicylic acid. Record the mass of the salicylic
acid sample in Table 1 and put the sample into a clean,dry 10-cm test tube.
3. Carefully add 12 drops of acetic anhydride and 2 drops of concentrated sulfuric acid to the salicylic
acid sample and agitate the tube to mix the contents. Put the tube into the water bath.
4. Allow the tube to remain in the hot water bath for 15 - 20 minutes. Agitate the tube several times
during the first 5 minutes to make certain all the solid is dissolved.
5. When the reaction occurred completly, remove the tube from the bath and add 32 drops of ice water, 5
drops at a time, with agitation between each 5-drop addition. After the water addition is completed, put
the tube into a mixture of ice and water contained in a small beaker. Allow the tube to cool in the ice-and-
water bath for 5 mins.
6. After 5 minutes, remove the tube from the cooling bath and observe its appearance. If you can see
distinct crystals of solid forming, put the tube back into the ice-and-water bath for another 5 to 10
minutes. If the test tube contents appear uniform and milky, it means your aspirin has not crystallized. Try
to get it to crystallize by stirring the mixture with a small spatula or glass stirring rod and, while
stirring,scratching the inside surface of the tube with the spatula or stirring rod. Continue this stirring and
scratching for a minimum of 5 minutes or until the sample begins to crystallize, whichever comes first.
7. If your sample begins to crystallize, return it to the ice-and-water bath for 5 to 10 minutes. If it does not
begin to crystallize after 5 minutes of stirring and scratching, inform your instructor, who will give you
directions for adding a few seed crystals of aspirin to start the crystallization. Once crystallization has
been started, return the tube to the ice-and-water bath for 5 to 10 more minutes of cooling.
8. After the cooling is completed, remove the tube from the cooling bath and filter the crystals by filter
paper pre-weighed (m0) with help of funnel. Pour all the suspension in the flask into the funnel. Wash the
solid in funnel by 15ml of ice water. Wait for 10 mins to be sure that most of the liquid is removed out.
9. Prepare a dish, weigh the dish and record the number in Table 1. Collect the sample in to a dish and
put in oven for totally dried.
10. After the sample has dried for 20 minutes, remove the dish and allow it to cool for 2 to 3 minutes,
weigh again (m1) the dish on the same blance and record the combined mass in Table 1.

B. Synthesis of Oil of Wintergreen

Methylsalicylate (oil of wintergreen) is an ester in which the carboxyl group of the salicylic acid has
reacted with the alcohol group of methyl alcohol. Interestingly, oil of wintergreen is used both as a topical
analgesic in rubs for sore muscles and as a flavoring agent.

Procedure
1. Place 0.1 g of salicylic acid into a clean, dry 10-cm test tube.
2. Add 6 drops of methyl alcohol and agitate the tube until the contents are well mixed.
3. Then add 1 drop of concentrated sulfuric acid.
4. Agitate the tube contents and place the tube in a beaker of boiling water for 3 minutes.
5. After the heating is completed remove the tube from the bath and add 15 drops of water to the tube
contents.
6. Cautiously note the odor of the products in the test tube by passing the tube back and forth under your
nose, slowly bringing it closer to your nose until you can detect the odor. Record the odor in Table 3.

CALCULATIONS AND REPORT

The percentage yield of a synthesis is defined by the following equation:

The actual yield is the mass of product isolated, and the theoretical yield is the mass of product that was
theoretically possible based on the amount of reactants used. In this synthesis, salicylic acid with a
molecular weight of 138 was reacted with an excess of acetic anhydride. Because the acetic anhydride
was used in excess, the amount of aspirin product theoretically possible is determined by the amount of
salicylic acid (the limiting reactant) used. Aspirin has a molecular weight of 180.

According to the equation, 1mol salicylic acid will react to produce 1molaspirin. Thus, if 138 g of
salicylic acid were reacted, the amount of aspirin that would theoretically be produced (the theoretical
yield) would be 180 g. The theoretical yield corresponding to any amount of reacted salicylic acid can be
calculated by multiplying the number of grams reacted by the factor 180 g aspirin/138 g salicylic acid.
Thus, the theoretical yield of aspirin is given by the following equation:

1. Use the mass of salicylic acid used and recorded and calculate the theoretical yield of aspirin. Record
the value in Table 2.
2. Use the mass of the empty filter paper and the filter paper plus aspirin recorded to calculate the mass of
aspirin you isolated. Record this mass in Table 2.
3. Use the results of steps 1 and 2 and equation to calculate the percentage yield for your synthesis of
aspirin. Record the calculated value in Table 2.

B. Synthesis of Oil of Wintergreen

List in Table 3 at least two commercial products in which you have detected the odor of oil of
wintergreen.
 Lab Report: The Synthesis of Aspirin and Other Esters
EXP. NUMBER SUBJECT DATE

NAME COURSE

A. Synthesis of Aspirin (12 pts)

Table 1 (4 pts)

Mass of salicylic acid used

Table 2 (8pts)

Theoretical yield

Mass of aspirin isolated

Percentage yield

B. Synthesis of Oil of Wintergreen (5 pts)

Table 3 (5 pts)

Odor of prepared ester

Commercial products containing oil of

C. Questions (3 pts)

1.Your prepared aspirin probably gave a positive test for phenol. How can this be explained?
a. The aspirin structure contains a phenol group.
b. It is contaminated with salicylic acid.
c. It is contaminated with acetic anhydride.
d. It is contaminated with sulfuric acid.
Explain your answer:
2.Suppose in Part A, a student washed the solid aspirin with hot water instead of ice water. How would
this influence the percentage yield of the isolated aspirin compared to that obtained if ice water had been
used?
a.Increase it. b.Decrease it. c.Would not influence it.
Explain your answer:

3.Suppose in Part A, a student suspended the synthesized aspirin using hot water instead of ice water.
How would this influence the percentage yield of the isolated aspirin compared to that obtained if ice
water had been used?
a.Increase it. b.Decrease it. c.Would not influence it.
Explain your answer:

4. Devise a synthetic route to obtain salicylic acid from benzene.

5. Devise a synthetic route to obtain aspirin from oil of wintergreen.