Synthesis of Acetaminophen
Introduction
Acetaminophen was first introduced in 1955 (Richman, 2004). It is an over-the-counter drug
that relieves pain and reduced fevers. Acetaminophen is considered an alternate to aspirin
since it does not irritate the stomach (Richman, 2004). It also has very low toxicity is it is used
properly. Acetaminophen is cheap and easily obtainable from any pharmacy. Acetaminophen is
created when the amine group of p-aminophenol is acetylated by acetic anhydride. This creates
an amide functional group and the by-product of this reaction is acetic acid. The crude
acetaminophen will form as a white solid after the acetylated reaction. To turn this crude
acetaminophen into a purified form, the recrystallization technique will be used. The
recrystallization technique is when the solid is dissolved and forced to precipitate as a crystal
solid later on. The crude solid is dissolved through heating with a small amount of solvent, in
this case, deionized water. The solution is then cooled to room temperature and later put into
an ice bath which is when the crystals form. These crystals obtained are more pure since the
impurities are dissolved in the cold solution. When cooling, the solution should remain
undisturbed. The purpose of this experiment is to determine the melting points of the crude
and purified form of acetaminophen using a MelTemp melting point apparatus. Using capillary
tubes, samples of the crude and purified solid will be tested. If the experiment is done properly,
the crude solid should dissolve faster than the purified solid of acetaminophen. One must wear
goggles and gloves at all times while working with acetic anhydride as it is corrosive.
http://de.academic.ru/pictures/dewiki/83/Synthesis_of_paracetamol.png
http://de.academic.ru/pictures/dewiki/83/Synthesis_of_paracetamol.png
Procedure
The experimental procedure used for this experiment was outlined in the CHEM 123L lab
manual, Experiment #1, Synthesis of Acetaminophen, pages 12-15. A slight change was made to
the one material that was used. Instead of a 100mL round bottom flask a 50mL round bottom
flask was used. Other than that, all steps were followed accordingly.
Experimental
*
Observations
Initial
p-aminophenol:
3.00g
* 36mL of deionized water was added to the Erlenmeyer flask for the recrystallization
technique.
Table
1:
Outcomes
of
Crude
and
Purified
Solids
Crude|
Purified|
Erlenmeyer Flask| Total Mass| Mass of Solid| Erlenmeyer Flask| Total Mass| Mass of Solid|
92.68g|
96.28g|
3.60g|
92.82g|
95.66g|
2.84g|
Melting
Point:
162
°C|
Melting
Point:
164
°C|
*This table shows how much of the solid was obtained after the reaction along with their
boiling points. This table can be used to see the difference between crude and purified solids.
Results
and
Calculations
p-Aminophenol + Acetic Anhydride Acetaminophen + Acetic Acid C6H7NO(S) + C4H6O3(l)
C8H9NO2(s)
+
C2H4O2(aq)
Crude|
|
|
Discussion
Purified|
|
|
The objective of this experiment was to find the melting points of the crude and purified solid.
After conducting the experiment, it was found that the crude solid melted faster than the
purified solid. Our values showed that our samples melted at a slightly lower temperature than
what the Merck Index had stated. The Merck Index said that the melting point varies from
169°C -170°C. The melting points we had observed were from 162°C -164°C. This might be due
to the fact that this experiment was not done under perfect conditions. Also, what we found in
terms of how much acetaminophen was obtained, was that the crude product was obtained in
larger amounts than purified. From the initial amount of p-aminophenol, which was 3.00g, we
achieved 3.60g of crude solid and 2.84g of purified solid. This solidifies the theory that the
impurities would have dissolved in the deionized water which is why the mass is lower for the
purified solid. There were very few, if any, errors made during this lab.
Questions
1. a) If 20 mL of water were added for every 1g of crude product then crystallization would
occur in less quantity or not occur at all. As the solution is dissolved, heated, and later cooled,
the impurities of the solution remain in the solution. As more solvent is added, more of the
product will remain in the solution rather than crystallizing; hence, a much lower yield would be
obtained.
b) If 5mL of water were added for every 1g of crude product then one of two things would
happen; the solid would not dissolve or the impurities would still be present within the product.
The solvent is used to dissolve all the impurities of the crude product and if less solvent is
available,
the
impurities
would
remain
within
the
product.
c) If room temperature solvent was used rather than cold solvent then more of the product will
remain in the solution. As temperature increases, solubility also increases in most cases, which
would keep some of the product dissolved resulting in a lower yield.
2. a) An organic compound is any compound that contains carbon, generally, are large chains of
carbon that are covalently bonded. They can be gaseous, liquid or a solid (Seager; Slabaug,
2004).
b) An amine is an organic compound/functional group that is derived by replacing one or more
of its hydrogen atoms in ammonia by another organic group. You may have a primary,
secondary or tertiary amine according to how many hydrogens are reduced (Hine, Elizabeth,
2008).
c) An amide is an organic compound/ functional group that contains nitrogen and is considered
to be a derivative of ammonia. It is grouped with a carbonyl (Newton, 2004).
3. Tylenol got its name from p-aminophenol. Since tynenol is made up of p-aminophenol the
name can be found within the word, “paraceTYLaminophENOL (Richman, 2004). The paminophenol is a crucial part to the creation of acetaminophen; hence, it was appropriate to
name
the
brand
“Tylenol”.
Conclusion
The purpose of this experiment was to determine the melting points of the crude and purified
sample of acetaminophen. Through this, it was found that the crude solid melted faster than
the purified solid that is what is supposed to happen ideally. The recrystallization technique was
also proven affective since the mass of the solid decreased showing that the impurities were
dissolved in the solution. This experimental method is highly effective as the values are
generally accurate. There are not many areas where one can make mistakes as well which
compliment the efficiency of this experiment. The main error possible in this experiment would
be reading the temperature at which the solid melts; however, that is not in the experiment, as
that would depend on the experimenter. Overall, this experiment was constructed fairly well
giving
values
that
solidify
the
theories
behind
this
experiment.
References
1. Hine, R.; Martin, E. A Dictionary of Biology, 6 ed.; Oxford University Press: Oxford, 2008, pp.
13) 2. Newton, D.E. Amides. The Gale Encyclopedia of Science [Online] 2004, 1, pp. 159. 3.
Richman, J.P. Analgesia. The Gale Encyclopedia of Science [Online] 2004, 1, pp. 181. 4. Seager,
S.; Slabaug, M. Chemistry for Today: General, Organic, and Biochemistry, Thomson Brooks/Cole:
Ogden, 2004, pp.342. 5. Stathopulos, S. Department of Chemistry 2013 First Year Chemistry
(CHEM 123L) Laboratory Manual; University of Waterloo: Waterloo, ON, 2013; pp. 12-15.