Separation of Active Components from Excedrin ES
Purpose:
The purpose of this lab is to determine the amount of acetaminophen, aspirin, and
caffeine in Excedrin ES tablets. To accomplish this, you will take advantage of the
different chemical characteristics of these three components. From the structures below,
you can see that aspirin contains a carboxylic acid group, while the caffeine contains
several amine functionalities. So it should be relatively easy to dissolve these two
components in an organic solvent and then extract them with an aqueous acid or base.
amine
nitrogens
The acetaminophen on the other hand, only contains a phenol (OH directly attached to an
aromatic ring) and an amide functionality. Both of these functionalities tend to be neutral
under acid/base conditions. At first glance, you might look at the amide group and think
it should be basic because it contains an amine like nitrogen. However, a contributing
resonance form for amides, shown below, causes the nitrogen to be electron deficient
compared to amines. The electropositive nature of amide nitrogens makes them much
less basic than amines.
Based on these two properties, we can develop a scheme to separate these three
compounds. First, use an organic solvent to dissolve the aspirin, and the caffeine. Since
the acetaminophen is less soluble in organic solvents, it has effectively been isolated from
the other two. Now we will extract the organic layer with an aqueous acid. The acid will
react with the caffeine to produce a salt that is water soluble. Remove the aqueous layer
and make it basic to regenerate the caffeine. The caffeine is once again soluble in
organic solvent and so can be separated from the aqueous phase. Finally, extract the
original organic layer with an aqueous base. It will react with the aspirin to produce a
salt that is water soluble. Remove the aqueous layer and make it acidic to regenerate the
aspirin. The aspirin is once again soluble in organic solvent and so can be separated from
the aqueous phase.
Unfortunately, there is no such thing as a 100% efficient extraction. Because of this you
will not extract all of the original components. In addition, each crude product you
collect will contain small amounts of one or more of the other compounds. To further
purify you crude compounds, you will need to recrystallize them using the procedures
you learned in previous labs.
Procedure:
Isolation of Components (Solvent Extraction):
1. Accurately weigh a tablet of Excedrin ES and pulverize it with a mortar and
pestle.
2. Transfer 400 mg of this powder into a clean, dry 15 mL conical centrifuge tube.
Label this tube ‘EXCEDRIN’.
3. Add 5 mL of methylene chloride (Note: methylene chloride is a suspected
carcinogen, handle with care!), cap securely, and shake for a minute with
occasional venting. Not all of the material will dissolve (acetaminophen, and any
binders and fillers).
4. Filter the resulting suspension through a ‘ChemWipe’ loosely placed at the top of
a glass funnel into a small beaker. Wash the trapped solids with two 2mL
portions of CH2Cl2 and collect the washing in the beaker. Save the ‘ChemWipe’
containing the acetaminophen and binders for step 6
5. Carefully transfer all of the liquid in the beaker to another clean, dry 15 mL
conical centrifuge tube. Label this tube '
ASP/CAF'
.
6. Place a small (50mL) beaker under the funnel containing the ‘ChemWipe’ and
add ~2mL acetone to the ‘ChemWipe’ to dissolve any acetaminophen. Allow the
acetone to collect in the beaker. Repeat 2X with 2mL portions of acetone.
Transfer the combined acetone fractions in the beaker to a large (pre-weighed)
watch glass and allow the acetone to evaporate on a warm hot plate (setting ~ 2).
7. Obtain the weight of the solid that remains on the watch glass.
8. Add 2 mL of 5% hydrochloric acid to the combined methylene chloride in the
'
ASP/CAF'centrifuge tube from step 5. Cap securely, and shake for a minute
with occasional venting.
9. Centrifuge the tube and use a disposable pipet to transfer the aqueous layer into a
clean, dry 15 mL conical centrifuge tube. Label this tube '
CAF'
. Save the
methylene chloride portion is the original tube.
10. Repeat Steps 12 - 13 two more times and combine the aqueous extracts in tube
'
CAF'
.
11. Add 10% sodium hydroxide to the hydrochloric acid extract in '
CAF'until it is
basic. Remember: do not dip pH paper into your solution, instead, use a
disposable pipet and place a drop on the pH paper.
12. Add 2 mL of methylene chloride to the '
CAF'tube, cap securely, and shake for a
minute with occasional venting.
13. Use a disposable pipet to transfer the methylene chloride to another clean, dry 15
mL conical centrifuge tube. Label this tube '
CAF-2'
.
14. Repeat Steps 12-13 two more times and combine the methylene chloride extracts
in tube '
CAF-2'
.
15. Dry the methylene chloride extracts with a small amount of anhydrous
magnesium sulfate. When the solvent is dry, a small amount of the solid should
easily disperse in the solvent. If not, add an additional amount of MgSO4.
Centrifuge to separate the drying agent.
16. Use a disposable pipet to transfer the liquid to a pre weighed watch glass.
17. Gently heat the watch glass to remove the methylene chloride (Note: be sure to
position your snorkel hood to remove the methylene chloride vapors).. Weigh to
constant dryness. This solid is your crude caffeine.
18. Since the caffeine has been removed, the methylene chloride from step 9 in the
'
ASP/CAF'tube now only contains aspirin. Dry it with magnesium sulfate,
centrifuge, and gently heat to remove the methylene chloride. This is your crude
aspirin
19. Recrystallize your crude products and check their identity and purity using m.p.
(normal and mixed), and FTIR.
20. Turn in your recrystallized products in labeled, tightly sealed containers. Be sure
to include the following information on each label:
Your Name:
Class/Section:
Compound:
M.P./ B.P.:
Actual Yield (g):
Theoretical Yield (g):
Date:
Percent Yield:
Remember: because caffeine sublimes so readily, you must seal your melting point tube
to determine the proper melting point.
Results:
•
•
•
•
Report the amount and weight percent of aspirin in Excedrin ES. Also comment
on its purity by comparing its m.p. and IR to literature values.
Report the amount and weight percent of acetaminophen in Excedrin ES. Also
comment on its purity by comparing its m.p. and IR to literature values.
Report the amount and weight percent of caffeine in Excedrin ES. Also comment
on its purity by comparing its m.p. and IR to literature values.
Did the weight of all three components add up to the weight of the tablet? Why?
(Updated 10/24/2004)