Chapter 24 Experiment B:

Aspirin Synthesis and Analysis

OBJECTIVES:

To synthesize aspirin
To determine the purity of the synthesized aspirin or a commercial aspirin tablet

INTRODUCTION:
Pure aspirin, chemically called acetylsalicylic acid, is both an organic ester and an organic acid. It is used extensively as a
painkiller (analgesic) and as a fever-reducing drug (antipyretic). When ingested, acetylsalicylic acid remains intact in the
acidic stomach, but in the basic medium of the upper intestinal tract, it hydrolyzes forming the salicylate and acetate
ions.

The analgesic action of aspirin is undoubtedly due to the salicylate ion; however, its additional physiological effects and
biochemical reactions are still not thoroughly understood. It is known that salicylate acid has the same therapeutic
effects as aspirin; however, due in part to the fact that it is an acid, salicylic acid causes a more severe upset stomach
than does aspirin.
Aspirin (molar mass of 180.2 g/mol) is prepared by reacting salicylic acid (molar mass of 138.1 g/mol) with acetic
anhydride (molar mass of 102.1 g/mol). Aspirin, like many other organic acids, is a weak monoprotic acid.

Qualitatively, the purity of an aspirin sample can be determined from its melting point. The melting point of a substance
is essentially independent of atmospheric pressure, but it is always lowered by the presence of impurities. The degree
of lowering the melting point depends on the nature and the concentration of the impurities.
Quantitatively, the purity of an aspirin sample can be determined by a simple acid-base titration. The acetylsalicylic acid
reacts with hydroxide ion, from a standardized sodium hydroxide solution, accordingly.

The volume and molar concentration of a standardized NaOH solution titrate the acetylsalicylic acid to the
phenolphthalein endpoint, where:
volume of NaOH (L) molar concentration of NaOH (mol/L) = mol NaOH
According to the diagram of the acetylsalicylic acid/hydroxide reaction, one mole of OH reacts with one mole of
acetylsalicylic acid: thus, the moles of acetylsalicylic acid in the prepared sample are calculated. Using the known molar
mass of acetylsalicylic acid the measured mass of the acid and the percent purity of the aspiring sample can be
calculated:
mol acetylsalicylic acid 180.2 g/mol = g acetylsalicylic acid
% purity

g acetylsalicylic acid

g aspirin sample

100

In the final part of this experiment (part C), the analysis for the percent acetylsalicylic acid in an aspirin sample can be
performed on the aspirin prepared in part A or on a commercial aspirin tablet.

PROCEDURE OVERVIEW:
Crystalline aspirin is synthesized and then purified by the procedure of recrystallization. The melting point and the
percent purity of the aspirin are measured, the latter by titration with a standardized NaOH solution.
A. Preparation of Aspirin
It is safest to prepare the aspirin in a fume hood. Set up a boiling water bath in a 400-mL beaker. Prepare about 100 mL
of deionized ice water. Also, set up an ice bath.
1. Mix the starting materials and heat.
Measure about 2 g ( 0.01 g) of
salicylic acid (caution: this is a skin
irritant) in a dry 125-mL Erlenmeyer
flask. Cover the crystals with 4-5 mL
of acetic anhydride (caution: acetic
anhydride is a severe eye irritant
avoid skin and eye contact). Swirl the
flask to wet the salicylic acid crystals.
Add 5 drops of concentrated sulfuric
acid to the mixture and gently heat
the flask in a boiling water bath for 510 minutes (caution: sulfuric acid
causes severe skin burns).
2. Cool to crystallize the aspirin. Remove
the flask from the hot water bath and,

to the reaction mixture, add 10 mL of deionized ice water to decompose any excess acetic anhydride. Chill the
solution in an ice bath until crystals of aspirin no longer form, stirring occasionally to decompose residual acetic
anhydride. If an oil appears instead of a solid, reheat the flask in the hot water bath until the oil disappears
and again cool.
3. Separate the solid aspirin from the solution. Set up a vacuum filtration apparatus and turn it on. Seal the
filter paper with water in the Buchner funnel. Decant the liquid onto the filter paper; minimize any transfer of
the solid aspirin. Some aspirin, however, may be inadvertently transferred to the filter; thats okay.
4. Wash and transfer the aspirin to the filter paper and wash. Add 15 mL of ice water to the flask, swirl, and chill
again. Repeat until the transfer of the crystals to the vacuum filter is complete; maintain the vacuum to dry the
crystals as best as possible. Wash the aspirin crystals on the filter paper with 10 mL of ice water. Keep all of the
filtrate until the aspirin has been transferred.
If aspirin forms in the filtrate, transfer the filtrate and aspirin to a beaker, chill in an ice bath, and vacuum filter
as before, using a new piece of filter paper.
Disposal: Dispose of the filtrate in the sink or as directed by your laboratory instructor.
5. Recrystallize the aspirin. Transfer the crystals from the filter paper to a 100 mL beaker. Add repetitive small
volumes of ethanol (e.g. 3 mL volumes) to the aspirin until the crystals just dissolve (20 mL is required). Warm
the mixture in a 60 C water bath (caution: no flame use a hot plate or a hot water bath). Pour 50 mL of 60 C
water into the solution. If a solid forms, continue warming until the solid dissolves. Cover the beaker with a
watchglass, remove it from the heat, and set it aside to cool slowly. Set the beaker in an ice bath. Beautiful
needle like crystals of acetylsalicylic acid form.
6. How much did you prepare? Vacuum filter the crystals on filter paper, the mass of which has been previously
measured ( 0.01 g). Wash the crystals with two 10 mL volumes of ice water. Place the filter paper and aspirin
sample on a watchglass and allow them to air-dry. The time for air-drying the sample may require that it be left
in your lab drawer until your next laboratory period. Determine the mass of the dry filter paper and sample.
Dispose of the filtrate in the sink.
7. Correct for residual solubility. The solubility of acetylsalicylic acid is 0.25 g per 100 mL of water. Correcting for
this inherent loss of product, calculate the percent yield.
8. What do you do with it? Dont use it for a headache! Place the sample in a properly labeled test tube, stopper,
and submit it along with your report sheet to your laboratory instructor at the conclusion of the experiment.
B. Melting point of the Aspirin Sample
1. Prepare the sample. Fill a capillary
melting point tube to a depth of 1 cm with
the recrystallized aspirin prepared in part
A6. Attach the tube to a 360 C
thermometer with a rubber band. Place
the sample alongside the thermometer
bulb. As the melting point for aspirin is
greater than 100 C, oil must be used for
the heating bath.
2. Determine the melting point. Slowly and
gently heat the oil bath at a rate of 5 C
per minute until the aspirin melts

(caution: the oil bath is at a temperature greater than 100C do not touch!). Cool the bath and aspirin to just
below the approximate melting point until the aspirin in the tube solidifies; at a slower 1 C per minute rate,
heat again until it melts; this is the melting point of your prepared aspirin.
3. Repeat the melting point measurement. Again, cool the bath and aspirin to just below the melting point until
the aspirin in the tube solidifies; at a 1C per minute rate, heat again until it melts.
Disposal: Ask your instructor about proper disposal of the oil. Be sure the oil is cool when handling it. Dispose of the
capillary tube in the Waste Glass container.
C. Percent Acetylsalicylic Acid in the Aspirin Sample:
Three trials are to be completed in the analysis of the aspirin. Prepare three clean 125 or 250 mL Erlenmeyer flasks and
determine the mass of three aspirin samples while occupying the balance. Obtain a 50 mL buret.
1. Prepare the aspirin sample for analysis. Assuming 100% purity of your aspirin sample, calculate the mass of
aspirin that requires 20 mL of 0.1 M NaOH to reach the stoichiometric point. On weighing paper measure the
calculated mass ( 0.001 grams) of the aspirin you have just prepared (or a crushed commercial aspirin tablet)
and transfer it to the flask. Add 10 mL of 95% ethanol, followed by about 50 mL of deionized water, and swirl to
dissolve the aspirin. Add 2 drops of phenolphthalein indicator.
2. Prepare the buret for titration. Prepare a clean buret, rinse, and fill it with standardized 0.1 M NaOH solution.
Be sure that no air bubbles are present in the buret tip. After 10-15 seconds, read and record the volume, and
the actual molar concentration of the NaOH solution.
3. Titrate the sample. Slowly add the NaOH solution from the buret to the dissolved aspirin sample until the
endpoint is reached. The endpoint in the titration should be within one-half drop of a faint pink color. The color
should persist for 30 seconds. Read and record the final volume of NaOH the buret.
Disposal: Discard the test solution in the waste acids container or in the sink followed by a generous supply of tap
water. Ask your instructor.
Cleanup: Discard the NaOH titrant into a properly labeled bottle; rinse the buret with several 5 mL volumes of tap
water, followed by two 5 mL volumes of deionized water.

Prelaboratory Assignment

NAME: __________________________

Answer the following questions.

1. A 0.409 g sample of aspirin prepared in the laboratory is dissolved in 95% ethanol, diluted in water, and titrated to
the phenolphthalein endpoint with 22.1 mL of 0.0994 M NaOH.
a. How many moles of acetylsalicylic acid are present in the sample?

b. What is the percent purity of acetylsalicylic acid in the aspirin sample?

2. The aspirin that is synthesized in the experiment is purified by a recrystallization procedure. In general terms
describe what is involved in a recrystallization procedure.

3. What is the active ingredient in aspirin? Why is it not ingested directly?

4. In this experiment 2.00 g of salicylic acid reacts with an excess amount of acetic anhydride. Calculate the theoretical
yield of acetylsalicylic acid for synthesis.

5. By using a handbook or the World Wide Web, look up the melting point of pure aspirin. Reference the location of
your source.

6. Describe the procedure for seating the filter paper in the funnel for a vacuum filtration.