470 Journal of Chemical Education • Vol. 75 No. 4 April 1998 • JChemEd.chem.wisc.edu
In the Laboratory
A Guided Inquiry Approach to NMR Spectroscopy
Laura E. Parmentier, George C. Lisensky, and Brock Spencer
Department of Chemistry, Beloit College, Beloit, WI 53511
We have developed a novel way to introduce NMR spec-
troscopy into the general chemistry curriculum as part of a
week-long aspirin project in our one-semester introductory
course entitled “The Structure and Properties of Materials”.
In a guided-inquiry-based experiment, students use research-
quality instruments and work in collaboration with other
students to develop a correlation chart for NMR chemical
shifts. Using this chart, they are able to interpret the NMR
spectra of their aspirin product.
The Experiment
Aspirin is synthesized by reacting salicylic acid and acetic
anhydride in the presence of a phosphoric acid catalyst (eq
1).1 Salicylic acid (2.00 g), 5.0 mL of acetic anhydride, and
5 drops of 85% phosphoric acid in a 125-mL Erlenmeyer
flask are maintained at 75 ° C in a water bath for 15 min.
Two milliliters of water is added to decompose any unreacted
acetic anhydride, producing some hot acetic acid vapor; then
the flask is removed from the water bath and 20 mL of water is
added to the reaction mixture. After cooling for a few minutes
in air, during which time crystals of aspirin should begin to
form, the flask is put in an ice-water bath to hasten crystalli-
zation. The product is isolated by vacuum filtration, washed
with three 5-mL portions of ice-cold water, and then dried
at 70 ° C. Purity, as percent acetylsalicylic acid content, is
determined by titration with NaOH to the phenolphthalein
endpoint. Purity of the aspirin product is also determined
qualitatively using IR and NMR spectroscopy.
OH
C
O
OH C CH3
O
O
C
O
CH3
O
C
O
OH
C
O
CH3 CH3 C
O
OH+ +
H3PO4
salicylic acid acetic anhydride aspirin acetic acid
(1)
WARNING: Acetic anhydride and phosphoric acid are cor-
rosive. Avoid skin contact and wear eye protection.
Students obtain and compare the IR and NMR spectra
of the aspirin product they synthesized to a series of refer-
ence spectra obtained by the class as a whole. IR spectra were
obtained using a Mattson Galaxy Series 3000 FTIR spectrom-
eter. Samples were run in mineral oil (or neat, for some ref-
erence compounds), and scans were from 4000 to 500 cm{1.
A Varian Gemini 200 MHz NMR spectrometer was used
for 1H spectra. Samples were run in CHCl3-d as solvent and
scans were from 0 to 12 ppm. From earlier experiments, our
students have some experience identifying major C–H, C–O,
and O–H stretching and bending frequencies in the IR
spectrum. Using the tables of IR vibrational frequencies
from previous experiments, they are able to identify the major
peaks in the IR spectrum of their aspirin product. NMR spec-
troscopy, however, is a new concept.
To facilitate interpretation of the aspirin spectrum, we
start the NMR portion of the experiment by having the stu-
dents collect 1H NMR spectra of a series of reference com-
pounds chosen to include some of the structural features
of aspirin: benzoic acid, acetic acid, propionic acid, phenol,
ethanol, salicylic acid, phenyl acetate, benzene, cyclohexane,
acetone, 3-pentanone, ethyl acetate, benzaldehyde, propion-
aldehyde, and acetophenone. IR and NMR spectra are posted
in a common study room so that students have access to all
class data. Each student obtains both an NMR and an IR
spectrum of the aspirin product and either an NMR or IR
spectrum of one of the reference compounds to post for class
use. Spectra are run by the student under the supervision of
the instructor or a teaching assistant. Students weigh out 20
mg of their aspirin product into an NMR tube, fill the tube
to the specified depth with CHCl3-d, and place the sample
in the spectrometer. The instrument has been previously
shimmed by the instructor, so usually no additional shimming
is necessary. The spectrometer collects the data; students ad-
just amplitude and phase of the peaks and plot the spectrum.
With modern FTIR and FT-NMR instruments, indi-
vidual spectra can be obtained in five minutes or less. In our
experience, 24 students in a laboratory section have obtained
all of the needed spectra in less than 4 hours of lab time with
only modest waits to use an instrument (which also provides
time to discuss the instrument and spectral interpretation
while waiting for spectra to be printed). Since students run
the IR, NMR, or titration portions of the experiment in any
order, efficient use of the instruments is maximized, and
students spend less time waiting in line.
Figure 1. Student-run 200 MHz 1H NMR spectra in CHCl3-d for (top,
1a) acetone and (bottom, 1b) acetic acid. See questions 1–-5 in
the text.
a
b
JChemEd.chem.wisc.edu • Vol. 75 No. 4 April 1998 • Journal of Chemical Education 471
In the Laboratory
Students are then asked to analyze the data and develop
a correlation chart for chemical shifts in the NMR spectrum
(note that we are only interested in chemical shifts here and
do not introduce spin–spin splitting, which is largely obscured
by the chosen wide scan range anyway). The process, which
is done in small groups of students working together, is guided
by the following series of questions.
1. Based on its chemical structure, how many different
kinds of hydrogen atoms are present in acetone?
2. How many peaks are there in the NMR spectrum of
acetone (Fig. 1a)?
3. Based on its chemical structure, how many different
kinds of hydrogen atoms are present in acetic acid?
4. How many peaks are there in the NMR spectrum of
acetic acid (Fig. 1b)?
5. Based on your answers for questions 1 & 2, match the
peaks in the acetic acid spectrum with the appropriate
portion of the acetic acid chemical structure by drawing
the structure of acetic acid and labeling each group of
hydrogen atoms with the ppm of the corresponding
peak.
6. Look at the chemical structures of benzoic acid and
phenol. What structural feature do they have in common?
7. Look at the NMR spectra of benzoic acid and phenol
(Fig. 2). What range of peaks do the two spectra have
in common? Give the range in ppm.
8. Based on your answers to questions 6 & 7, give the
ppm value for the carboxylic acid peak in benzoic acid.
9. Based on your answers to questions 6 & 7, give the
ppm value for the alcohol peak in phenol.
This same type of reasoning is applied to the remainder
of the reference compounds. In doing so, students can iden-
tify the peaks in the NMR spectrum that correspond to some
Figure 2. Student-run 200 MHz 1H NMR spectra in CHCl3-d for
(top) benzoic acid and (bottom) phenol. See questions 6–9 in the
text.
Figure 3. Student-run 200 MHz 1H NMR spectrum in CHCl3-d for
aspirin. The broad carboxylic acid peak at 9.5 ppm is not always
observed
of the common functional groups, with particular emphasis
on those present in aspirin. Students are then asked to assign
the peaks in the NMR spectrum of their aspirin product and
to identify any impurities. They are further asked to relate
percent purity by titration with spectral results and percent-
age yield.
Discussion
We have found this discovery-based approach to NMR
spectroscopy to be very successful. Students are able to assign
unambiguously the peaks in their aspirin spectra (Fig. 3)
based on the compiled class data. Furthermore, common
impurities such as water, salicylic acid, or acetic acid can be
readily identified. Liquids (water) that do not mix with
CHCl3-d and adhere to the sides of the tube may lead to a
broad peak in the NMR spectrum between 4 and 5 ppm.
This may account for an overall yield calculated to be greater
than 100% and a calculated purity of less than 100%. The
presence of unreacted salicylic acid may be indicated by sev-
eral (usually small) peaks in the aromatic region of the NMR
spectrum that are not due to aspirin, and can often explain
why the titration calculations led to a purity of greater than
100%. The aromatic peaks of salicylic acid fit between the
aromatic peaks of acetylsalicylic acid in a 200-MHz spectrum.
Acetic acid CH3 also shows up nicely in some samples.
Relating spectral results with percent purity by titration
and percentage yield is an integral component of this experi-
ment. This focus encourages students to analyze their data by
applying concepts such as polarity, limiting reactant and acid–
base titration, which were learned in previous experiments.
This project is particularly appealing in that it involves the
synthesis and detailed analysis of a familiar material, aspirin, using
some of the powerful tools that practicing chemists routinely
use. Factors such as electronegativity and electron shielding
that affect NMR chemical shift are fairly well understood at
the introductory level. Combined with IR spectroscopy
(which we have found does not lend itself as well to this type
of inquiry analysis) and acid–base titration, the classic aspirin
synthesis experiment becomes a larger project that is well-
suited to the guided-inquiry-based introduction of NMR
spectroscopy.
Note
1. Experimental procedures for the synthesis of aspirin are avail-
able in most standard organic laboratory manuals—for instance
Campbell, B. N., Jr. & Ali, M. M. Organic Chemistry Experiments,
Microscale and Semi-Microscale; Brooks/Cole: Pacific Grove, CA, 1994.
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