Synthesis of Aspirin
Synthesis of Aspirin
Synthesis of Aspirin
A General Chemistry Experiment
John Olmsted III
Department of Chemistry and Biochemistry, California State University, Fullerton, Fullerton, CA 92834
recognition, as the reactions modify the periphery of a structural core common to the starting material, intermediate
product, and final product (Fig. 1).
Viewed from another perspective, this sequence exemplifies two of the most common types of chemical reaction,
hydrolysis and condensation:
HOC6H4 CO2CH3 + H2O HOC6H4 CO2H + CH3OH
Hydrolysis
As illustrated in Figure 2, the hydrolysis reaction proceeds in several steps involving deprotonation and protonation as well as cleavage of a CO bond (7). These encompass examples of Brnsted acidbase proton transfer, another
major class of chemical reactions.
These structural changes manifest themselves through
readily observed macroscopic changes as the synthesis proceeds. Addition of aqueous base to syrupy, fragrant oil of
wintergreen yields a white odorless solid. Upon heating, this
I. Deprotonation of oil of wintergreen
O
H
C
H
O
H
OH
H
H
CH3
C
H2 O
C
C
CH3
C
CH3
C
C
O
C
OH
O
H
C
H
Compound
R1
Oil of Wintergreen
CH3 H
R2
Reactive
sites
R2
C
H
Salicylic Acid
Aspirin
CH3
C
C
C
H
O
C
H
CH3OH
C
H
R1
C
The two-step conversion of oil of wintergreen (methyl 2hydroxybenzoate) into salicylic acid (5) and then into aspirin
(6 ) serves as an introductory example of multistep sequential synthesis. It also provides practice in molecular pattern
CH3
C
O
H
C
CH3
O
H
Common Core
C
C
O
C
2 H3O+
C
H
C
H
H
C
2 H2 O
C
H
Figure 2. Reaction mechanism for the conversion of oil of wintergreen into salicylic acid.
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In the Laboratory
1262
In the Laboratory
Infrared Characterization
Prepare a solution of each solid (salicylic acid and aspirin)
by placing about 1 mL of ethyl acetate in a clean, dry test
tube, adding a spatula-tip amount of solid, and stirring to
dissolve. Using a Pasteur pipet, transfer 45 drops of this
solution to a salt plate and allow the solvent to evaporate.
Place the salt plate on the mount in the sample compartment
of an FTIR spectrophotometer. Scan the spectrum and print
a copy. Clean the salt plate three times by placing several
drops of ethyl acetate on its surface and wiping thoroughly
with a clean lint-free tissue.
Include in your report for this experiment a one-paragraph
abstract, brief procedure, data and results, and discussion. In
the procedure, describe the details of what you did and
observations you made, but do not reproduce the procedure
from the laboratory manual. Data and results should include
all masses used, the theoretical yields of products, and the
percent yields of products. In the discussion, answer the
question What explains why my yields are different from
theoretical yields? Also compare the IR spectra of oil of
wintergreen and your two products and identify the peaks
that are unique to each of the products.
The use of FTIR in undergraduate laboratories is becoming increasingly prevalent as this technique becomes routine
and instruments are more affordable. Others have described
experiments using FTIR spectroscopy in general chemistry
for smog analysis (9) and for exploring Lewis structures (10).
The technique also finds applications in the organic laboratory
(11) and throughout the undergraduate curriculum (12). At
Fullerton we make use of FTIR not only in general chemistry
laboratory but also in our undergraduate organic, analytical,
and physical chemistry laboratories; and our students often
use the instruments in the course of their undergraduate
research projects.
The use of FTIR spectroscopy to differentiate aspirin from
other substances is not unique to this instructional exercise
in chemical synthesis. Procedures for quantitative analysis of
aspirin using FTIR have been reported for pharmaceutical
preparations (13) and drug testing (14). Furthermore, contemporary research utilizes FTIR to study aspirinDNA (15)
and aspirinRNA interactions (16 ). Thus, the qualitative
identification of aspirin by FTIR serves as a representation
of how modern spectroscopic techniques facilitate analytical
and physical research work.
Discussion
Acknowledgments
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