Acid-Catalyzed Synthesis of Aspirin from Salycylic

Acid and Acetic Anhydride

Ristovska, Anastazija*
Chemistry Department, Rice University, Houston, Texas
77005, USA
ar24@rice.edu
Received date

Salicylic acid was reacted with acetic anhydride under

acidic conditions to produce aspirin and acetic acid with
85.4% yield with respect to salicylic acid as the limiting
reagent. In an alcohol-anhydride esterification process, the
hydroxyl group of the salicylic acid formed an ester with
the acetic anhydride, leaving acetic acid as byproduct. A
three-fold recrystallization procedure was used to purify the
product. The 1H NMR analysis showed 97.35% purity of
the aspirin obtained.

The NMR analysis of 2-acetyloxybenzoic acid showed five

unique hydrogen atoms, three of which were very up-field
and thus shielded, coming from the methyl group of the
acetyl substituent. The hydroxyl hydrogen atom did not
appear at all in our 1H NMR analysis (whereas otherwise it
would had peaked around =12 ppm. The benzene ring
hydrogen ortho to the carboxyl group was found at =8.11
ppm, the one on the neighboring carbon was found at =7.6
ppm, and the hydrogen ortho to the ethanoate substituent to
the benzene ring was found at =7.14 ppm. The methane
hydrogens of the ethanoate substituent were noticed at
=2.35 ppm, not split by any other neighboring hydrogen
atoms, since there are none.
2-acetyloxybenzoic acid. 1H NMR (CDCl3, 400 MHz) :
2.35 (s, 3H), 7.14 (dd, J(H,H)=8, 0.8Hz, 1H), 7.26(s, 1H),
7.36 (td, J1(H,H)=7.6, 0.8Hz, J2(H,H)=8, 1.2Hz, 1H), 7.62
(td, J1(H,H)=8, 1.6Hz, J2(H,H)=8, 2Hz, 1H), 8.1 (m, 1H).

Scheme 1. Synthesis of Aspirin

8g of salicylic acid was heated in a 250-mL Erlenmeyer

flask with acetic anhydride and 3 drops of 85% phosphoric
acid for 2h. The temperature was controlled at 80-95C and
the solution was stirred at x350rpm. After 2h 10 mL
deionized water was added. The flask was removed from
the hot stir plate and was cooled first to room temperature
on the bench, and then to 0C in an ice-bath. The
precipitated product in the Erlenmeyer flask was vacuum
filtered. The aspirin product was isolated in vials that were
kept open in the drawer for one week, allowing more of the
water to evaporate. The purification recrystallization
procedure consisted of dissolving the aspirin crystals in 100
mL deionized water in a 250-mL beaker using a hot stir
plate to stir and heat the solution, bringing it to boiling
point at 95C and allowing it to boil for several minutes
until no more of the white solid crystals were observed. The
solution was removed from the hot stir plate and was left on
the bench to cool at room temperature. It was then added to
a water ice-bath, causing the formation of new crystals. The
aspirin was then vacuum filtered for a second time. The
steps of recrystallization were repeated three times, using a
temperature of 90-100C to dissolve the crystals each time.
The pure sample of aspirin was then placed in a desiccator
for 1H NMR analysis.

Figure1. 1H NMR (CDCl3, 400 MHz) Analysis of Aspirin Product

Supporting Information Available: For complete tables of

physical properties of the chemicals used, please visit
http://pubchem.ncbi.nlm.nih.gov.
Acknowledgements. We are grateful to V. Farrukh for NMR
data.
References. An example of the General Chemistry
Experiment for the synthesis of aspirin can be found at
http://pubs.acs.org/doi/abs/10.1021/ed075p1261
Olmsted III, John A. J. Chem. Educ., 1998, 75 (10), p 1261.
Publication
Date
(Web):
October
1,
1998
DOI:
10.1021/ed075p1261

Figure 2: 1H NMR (CDCl3, 400 MHz) Analysis of Aspirin Product