Separation of Active Components from Excedrin ES
Purpose:
The purpose of this lab is to isolate the active components present in Exedrin ES tablets,
namely acetaminophen, aspirin, and caffeine. 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 a basic N atom (circled). 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.
O
HN
HO
O
N
O
O
CH3
H3C
N
N
O
N
CH3
O
OH
CH3
caffeine
aspirin
(acetylsalicyclic acid)
CH 2Cl 2 soluble
CH3
acetaminophen
(p-hydroxyacetanilide)
CH 2Cl 2 soluble
CH 2Cl 2 insoluble
The acetaminophen contains a phenol (OH directly attached to an aromatic ring) and an
amide functionality. At first glance, the amide group may appear to be basic because it
contains a nitrogen atom. However, contributing resonance forms for amides results in
decreased electron density on the N atom, making the N less basic than amines. In
addition, acetaminophen has additional resonance forms which distribute the electron
density to carbon atoms, further reducing the basicity of the N atom. Phenols are slightly
O
H
N
O
CH3
H
+
N
-
CH3
H
O
O
O
H
+
N
CH3
H
+
N
+
N
CH3
-
HC
-
CH
-
C
OH
OH
OH
OH
OH
resonance forms of acetaminophen, showing increased positive charge on N atom compared to amines
acidic and many phenols are acidic enough to react with NaOH to form water soluble
salts. However acetaminophen and aspirin have different solublities in methylene
chloride and this difference can be used to separate acetaminophen from the other two
active ingredients in Excedrin ES.
CH3
Methylene chloride is not soluble in water and will form a separate liquid layer when
shaken with water and allowed to settle in a separatory funnel. The two phases can be
separated, thereby creating two fractions: one containing substances soluble in
methylene chloride and one containing substances soluble in water. By adjusting the pH
of the aqueous phase by adding NaOH or HCl, the nature of organic substance, and hence
its solubility in water, can be manipulated.
HO
+
O
Na
O
O
CH3
O
-
O
NaOH
O
CH3
HCl
water soluble
CH 2Cl 2 soluble
Cl
O
N
N
N
+
NH
N
H3C
O
O
CH3
CH 2Cl 2 soluble
CH3
HCl
NaOH
H3C
O
N
N
N
CH3
O
CH3
water soluble
.
You will use the properties described above to separate the components of
Excedrin ES. As you follow the procedure, you will use your knowledge of the
properties of each substance to determine the effect of each step on the separation scheme
and the identity of the component(s) present at each step of the scheme.
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.
Equipment/supplies
ExcedrinES:
2 tablets/student
3M NaOH
(~10mL/student)
25mL E. flasks
5/student
TLC plates
Methylene chloride
(~27ml/student)
aspirin standard
Ethanol
(~5 mL/student)
caffeine standard
small beaker
5/student
iodine chamber
1 hot plate/stirrer
stir bar
acetic acid/butyl
acetate developing
solvent
5% HCl
(~10mL/student)
acetaminophen
standard
boiling stick
(3/student)
Procedure
I
Sample Preparation
1. Carefully weigh 2 Excedrin ES tablets and grind the tablets into powder using a
mortar and pestle.
2. Transfer the resulting powder into a clean, 25 mL Erlenmeyer flask and add ~7
mL methylene chloride. (Note: methylene chloride is a suspected carcinogen,
handle with care!-keep the flask under a snorkel hood)
3. Add a magnetic stir bar and stir the contents on a magnetic stirrer/hot plate for 5
minutes with gentle warming. The caffeine and aspirin are soluble in the
methylene chloride whereas the acetaminophen and binders are not.
II Isolation of crude acetaminophen
4. Filter the material through a small Buchner funnel (pre-weigh the filter paper) and
wash the solids with ~5mL additional methylene chloride. (this helps remove any
methylene chloride soluble material still entrained (trapped) in the solids). Allow
the solids to dry for 5 minutes and then weigh the filter paper/solids. Determine
the mass of the solids. Label the solids ‘A’
5. While the solids in step 4 are drying, transfer the filtrate from step 4 to a
separatory funnel (make sure the stopcock is in the closed position). Label the
filtrate ‘B’
6. Transfer the solids ‘A’ in the funnel to a clean 25 mL Erlenmeyer flask and add
~5-7 mL ethanol. Add a boiling stick (provided) and gently boil the contents on a
hot plate. Filter the contents while still warm by gravity filtration (pre-weigh the
filer paper) into a small pre-weighed beaker and wash the contents of the filter
paper with ~ 5mL warm ethanol. Place the filter paper on a watch glass and allow
to air dry. Label the solids ‘C’. Obtain the weight of solids ’C’ when dry.
7. Concentrate the ethanol solution in the beaker to dryness by gently heating to a
boil. Be careful not to over heat the material. After cooling, weigh the contents of
the beaker. Calculate the amount of crude acetaminophen recovered. Label this
‘D’
III Isolation of aspirin
9. Add ~5mL 5% HCl to the separatory funnel described in step 5. Cap the
separatory funnel and invert the funnel. While in the inverted position, open the
stopcock to release any pressure buildup. Repeat this process once more, and
then agitate the funnel to thoroughly mix the contents. Open the stopcock once
more in the inverted position. Then close the stopcock and place the separatory
funnel in a ring support and allow the layers to separate.
10. Drain the methylene chloride layer into a clean 25mL Erlenmeyer flask; drain the
aqueous layer into another 25mL Erlenmeyer flask. Label the methylene chloride
layer ‘E’ and the aqueous layer ‘F’
11. Return the methylene chloride layer ‘E’ to the separatory funnel and repeat step 9.
12. Drain the aqueous layer from step 11 into flask ‘F’. Return the methylene chloride
layer to flask ‘E’
13. Remove trace amounts of water from the methylene chloride layer (E) by adding
small amounts of anhydrous magnesium sulfate (MgSO4) until the MgSO4 easily
disperses and remains suspended in the liquid. Allow the mixture to stand for 5
minutes.
14. Filter the MgSO4 suspension through a Kim-wipe placed in a short gravity funnel
suspended over a pre-weighed beaker. The Kim-wipe should remove the
magnesium sulfate. The filtrate in the beaker should be clear. If not, re-filter.
15. Evaporate the methylene chloride on a hot plate at low setting (2-3). Weigh the
solids that remain in the beaker (‘E’)
IV Isolation of caffeine
16. Transfer the contents of flask ‘F’ to the separatory funnel. Slowly add 10%
NaOH(aq) with gentle swirling until the solution is basic to litmus paper. (use a
glass rod to sample the mixture and touch the end of the rod to a piece of litmus
paper)
17. Add 5mL methylene chloride to the separatory funnel and shake the contents to
mix the contents. Allow the contents to settle into two phases.
18. Drain the methylene chloride layer into flask ‘G’
19. Add 5mL fresh methylene chloride to the contents of the separatory funnel and
repeat step 17.
20. Drain the methylene chloride layer into flask ‘G’; drain the aqueous layer into
flask ‘H’
21. Dry the methylene chloride layer and filter as described in steps 13-14 (make
sure to pre-weigh the beaker.)
22. Evaporate the methylene chloride layer as described in step 15 . Weigh the
residue (‘G’)
VI Purification of crude substances.
23. Re-crystallize the crude solid ‘D as follows: Add ~2-3mL water and heat to
near boiling. Add additional water slowly until the solids dissolve. Allow the
solution to cool and then place in an ice bath. Recover the solids by vacuum
filtration (Buchner funnel). Allow the solids to dry and obtain the mass.
24. Recrystallize the crude aspirin as follows: Add 2-3 mL of 95% ethanol to the
beaker containing the crude aspirin and warm (do not boil) the mixture to
dissolve the crystals. If the crystals do not all dissolve, add 2-3 mL more of the
ethanol and continue to warm the mixture. When the crystals are all dissolved,
add 8-10 mL of warm water, cover the beaker with a watch glass, and let the
solution cool slowly. Crystals of aspirin will form. Complete the
recrystallization by cooling in an ice bath.
25. Recrystallize the crude caffeine by adding just enough hot water to dissolve the
crude material. Allow the resulting solution to cool to room temperature. Place
the mixture in an ice bath to complete the recrystallization.
VII Charactaerization of isolated substances
26. Obtain melting points for each of the separated components of Excedrin ES.
Since caffeine sublimes readily, the capillary holding the caffeine sample
should be sealed by melting the end of the capillary tube in a flame.
Process Scheme
Asp=aspirin
asp, acet, caf, bind
Acet=acetaminophen
Caf=caffeine
CH 2Cl 2
bind=binders
insoluble
B
A
soluble
(filtrate)
HCl/ H2O
ethanol
aq sol
CH 2Cl 2
insoluble
C
D
soluble
(filtrate)
sol
E
F
NaOH/H2O/ CH2Cl 2
CH 2Cl 2
sol G
aq sol
H




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
or why not?
(Updated 10/18/2010)