Synthesis of Aspirin (Acetylsalicylic Acid)

Kunjal Patel
TA: Scott Plunkett
May 18, 2010

Purpose: To prepare acetylsalicylic acid via synthesis of salicylic acid

and acetic anhydride.

Procedure: 1 In a conical vial salicylic acid (0.210g, 1.52mmol), acetic

anhydride (0.480ml, 0.519g, 5.08mmol) were added and concentrated
phosphoric acid (1 drop) as a catalyst was added to the vial. The vial
was partially submerged in a (50 °C) hot water bath. The mixture in the
vial was stirred until the dissolution of solid. The vial was cooled to
room temperature (23°C). Once the crystals were evident in the
solution the vial was further cooled in ice water bath for complete
crystallization. The crystals were isolated using vacuum filtration
technique to yield white crystalline of acetylsalicylic acid (0.2143g,
1.189mmol, 78.2%): mp 128°C (lit2 134-136 °C).

Discussion: The synthesis of Acetylsalicylic acid using salicylic acid

and acetic anhydride under basic conditions yielded 78.2% white
crystalline solid. The melting point of the pure product was determined
to be 128°C, This could have some effect on the purity, for the melting
point of the harvested acetylsalicylic acid was not close to the
literature melting point Since the final product was determined not to
be very pure, it is highly likely that less than 0.2143g of the product
was acetylsalicylic acid. Further analysis of the product will have to be
done to determine exactly how pure the product actually was. There
were several problems that could have contributed to the low purity.
When dissolving the initial amount of salicylic acid in the solution of
acetic anhydride and concentrated phosphoric acid, it did not
completely dissolve into the solution, even
when it was heated. This could have a slight impact on the results of
the overall yield of aspirin because it was possible that not all of the
salicylic acid was synthesized. To determine if this affected the
synthesis of aspirin at all, the experiment should have been ran a
second. And the iron (III) chloride test also could have been ran to
determine if
any of the aspirin degraded to salicylic acid or never converted from
salicylic acid3. Another approach to synthesize aspirin would be using
CaCO3 with microwave irradiation during this procedure use of
Brønsted bases as catalysts with microwave irradiation improved the
yield, and reaction time. This seems contradictory because traditional
synthesis involves Brønsted acid as catalyst for higher yield and
reaction time because of the nature of the leaving group in the
reaction mechanism another way to improve yield was when
synthesizing aspirin with microwave irradiation without the use of
catalyst seemed to produce the highest yield (80%) and the reaction
was completed within 10-13minutes4. By omitting the use of solvents
for recrystallization in the previous procedures we can also introduce
the solvent-free principle and introduction to green chemistry.

__________________________________

Refrences

1 Paul,N. Organic Chemistry Lab – Chemistry 254; McGraw‐Hill: New York, 2009;
pp 155–162.
2 Sigma-Aldrich Chemical Catalog Online. http://www.sigmaaldrich.com/united-
states.html (accessed May 2010); Search: Product No. 132926.
3 Susan Baker. University of Main at Augusta.
http://faculty.uma.edu/sbaker/chy%20106%20asa.htm accessed May 2010.
4 David Sanabria, Marilyn García, Joaudimir Castro, and Johanna Fajardo.
University of Puerto Rico,
http://test.scheikundeinbedrijf.nl/content/Modules/Modulenaam/Files/p628.pdf
accessed May 2010.