October 20

CHM 337 Friday Section C 08

Separation and Purification of the Components of an Analgesic Powder

Purpose
This experiment aims to separate the three main active components (acetaminophen, aspirin, and
caffeine) and the inactive ingredients of a headache power by a combination of solubility differences
and a chemically active extraction.

Figure 1. The scheme of ingredient separation.

Procedure
The Organic Puzzle Book, pp. 10 -19. Method B was used in this experiment.

Observations and Data

(1) Melting point quality control and yield analysis:
Compound Name Mass (g) Observed M.P. (°C) Corrected M.P. (°C) Ideal M.P. (°C)
Analgesic Powder Mix 1.012 N.A. N.A. N.A.
Inactive Ingredients 0.140 N.A. N.A. N.A.
Acetaminophen 0.120 169 - 170 169 - 170 169 – 170.5
Aspirin 0. 223 139 - 140 139 - 140 138 - 140
Caffeine 0.012 220 - 222 220 - 222 235 - 237
Table 1. Melting point and mass of reactants and products. Benzoic acid was used as the calibration
standard. Observed m.p. was 122 – 123 °C while the ideal m.p. is 121 – 123 °C. Thus, no adjustments
were made to the observed m.p. in the Table 1.

Compound Name Mass (g) Expected Mass (g) Percent Recovery

Inactive Ingredients 0.140 1.012 – 0.52 – 0.26 – 0.0325 = 0.1995 0.140 / 0.1995 = 0.70
Acetaminophen 0.120 0.520 0.120 / 0.520 = 0.23
Aspirin 0.223 0.260 0.223 / 0.260 = 0.86
Caffeine 0.012 0.0325 0.012 / 0.0325 = 0.37

Table 2. Percent recovery of active and inactive ingredients

(2) Thin layer chromatography:

Solvent front: 7.25 cm

Rf = 6.75 cm / 7.25 cm = 0.93

Rf = 4 cm / 7.25 cm = 0.55

Rf = 1 cm / 7.25 cm = 0.14
0 cm

Figure 2. Thin layer chromatography result. The four columns are (a) analgesic powder mix, (b)
acetaminophen, (c) aspirin, and (d) caffeine. Rf values are calculated by (distance travelled by
component)/(distance travelled by solvent front).

As can be seen from Fig. 1, the spot is most intense for acetaminophen (Fig. 1b), followed by aspirin
(Fig. 1c) and caffeine (Fig. 1d). In the column of the power mix (Fig. 1a), the spot of the acetaminophen
is also the darkest, while caffeine and aspirin spots are much lighter. Similar relative spot intensity was
observed after TLC plate was stained in the iodine tank.

(3) Ferric chloride test:

Figure 3. Comparison of Method A (left) and Method B (right) aspirin product in the ferric
chloride test.

Discussion
1. Acetaminophen
As in Table 1, the m.p. for acetaminophen was within the ideal m.p. range, suggesting a relatively high
purity. Based on TLC (Fig. 2), the spot for acetaminophen (Fig. 2 b) corresponds well to one of the spot
in the power mix column (Fig. 2a). In addition, only one spot was observed for acetaminophen. This
confirms the high purity of acetaminophen. See Fig. 2 for Rf value of acetaminophen.

2. Caffeine
The caffeine m.p. was significantly lower than the ideal range. However, this might be because of the
small amount of caffeine that that was packed into the melting point capillary. Since the amount of
caffeine obtained was low and caffeine was spread out in the flask, it was difficult to pack enough
material for m.p. measure, which made the observation difficult and made the observed m.p. less
reliable. Thus, we cannot conclude that caffeine is impure using only the m.p. data.

In Fig. 2, Based on TLC (Fig. 2), the spot for caffeine (Fig. 2 d) corresponds well to one of the spot in
the power mix column (Fig. 2a). In addition, only one spot was observed for caffeine. This suggests that
caffeine is also pure, supporting the point that the caffeine m.p. was unreliable due to the small amount
packed in the capillary. See Fig. 2 for Rf value of caffeine.

3. Aspirin
As in Table 1, the m.p. for aspirin was within the ideal m.p. range, suggesting a relatively high purity.
Based on TLC (Fig. 2), the spot for aspirin (Fig. 2 b) corresponds well to one of the spot in the power
mix column (Fig. 2a). In addition, only one spot was observed for aspirin. After iodine visualization,
only one spot was visible in the aspirin column, and it still corresponded to the spot in the powder mix
column. TLC UV illumination and I2 visualization both suggest the high purity of aspirin. See Fig. 2 for
Rf value of aspirin.

Ferric chloride test (Fig. 3) further confirms that aspirin, instead of salicylic acid, was isolated. The
resulting solution of ferric chloride test would turn deep purple if salicylic acid is present. Ferric
chloride result (Fig. 3 right) showed that the aspirin that I obtained through method B did not contain
salicylic acid.

Overall, method B successfully separates and purifies acetaminophen, aspirin, and caffeine, and the
products are of high purity.

4. Percent recovery
Overall, the experiment yields decent percent recovery of inactive ingredients and aspirin (Table 2). The
percent recovery of acetaminophen and caffeine, the percent recovery is a bit low. For acetaminophen,
the relatively low percent recovery might be a result of insufficient recrystallization: under time
constraint, I was not able to wait for the acetaminophen to complete the recrystallization. For caffeine, I
did not finish the caffeine isolation in one lab section, and I left it in the methylene chloride layer over
the week. Since I didn’t dry the solution, the remaining base in water might have broken down some
caffeine, leading to the relatively low percent yield.
In conclusion, the experiment successfully separated the acetaminophen, caffeine, and aspirin with good
purity and yield.

Discussion Questions
1. My partner obtained salicylic acid (Fig. 3 left) through method A while I obtained aspirin through
method B. The main difference between the methods is that method A turns aspirin into salt by adding a
strong base, while method B turns caffeine into salt with a strong acid. Thus, adding NaOH to the
solution to produce sodium acetylsalicylate and then adding HCl to acidify the solution are the two steps
that are mostly likely responsible for the hydrolysis of aspirin.

From the mechanism of the hydrolysis of aspirin above, we can see that after aspirin is turned into salt
by strong base, the salt is unstable in water and would slowly reacts to form salicylic acid. By leaving
the salt in aqueous solution for too long, aspirin might be decomposed. To determine in which step the
hydrolysis happens, we can make two samples: For the first sample, we acidify the solution immediately
after mixing the solution with strong base. For the second sample, we acidify the solution after a delay.
If the second sample shows an increase of salicylic acid (which we can test by melting point or TLC),
then leaving the sodium acetylsalicylate salt in aqueous solution is indeed responsible for the hydrolysis
of aspirin.

2. When encounter water in the air, aspirin (acetylsalicylic acid) decomposes to salicylic acid and acetic
acid. Aspirin in an old bottle might have reacted with water in the air. The vinegar smell is from acetic
acid which is a product of the hydrolysis of aspirin.

3. If acetaminophen were soluble in methylene chloride, it would dissolve in DCM along with caffeine
and aspirin. After adding NaOH, there would be both the conjugate base of acetaminophen and sodium
acetylsalicylate salt in the aqueous layer since both are water soluble. To avoid this problem, we can
utilize the difference of acetaminophen and aspirin in their pKa. Since acetaminophen is a phenol and
aspirin has a carboxylic group, aspirin is a much stronger base and can be deprotonated with a relatively
weaker base. The pKa of aspirin is ~ 3.5 while the pKa of acetaminophen is ~ 9.9. Thus, we can use a
weak base (e.g. ammonia) to first deprotonate aspirin first. The acetylsalicylate salt will be in the aqeous
layer, leaving only acetaminophen and caffeine in the DCM layer. To further separate caffeine and
acetaminophen, we treat the solution with a strong base (e.g. NaOH) to deprotonate acetaminophen.
Then acetaminophen will be in the water layer and caffeine will be the only ingredient in the DCM
layer.

DCM: Aspirin,
acetaminophen, caffeine

Treat with weak base

e.g. ammonia

aqueous layer DCM layer

acetylsalicylate Acetaminophen & caffeine

salt
Treat with strong base
e.g. NaOH
Treat with HCl
aqueous layer DCM layer

Aspirin

Acetaminophen Caffeine in
conjugate base DCM

Evaporate
Treat with HCl DCM

Acetaminophen Caffeine