NMR study of the synthesis of 17O-enriched acetic acid by hydrolysis of acetic anhydride with 17O-enriched water

Article abstract of DOI:10.1002/mrc.1266

¹⁷O-enriched acetic acid (2.5% in ¹⁷O) was synthesized by hydrolysis of acetic anhydride with ¹⁷O-enriched water. The reaction was monitored by ¹⁷O and ¹H NMR spectroscopy. Acetic anhydride, ¹⁷

Full text of DOI:10.1002/mrc.1266

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2003; 41: 959–961
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1266
Note
17
NMR study of the synthesis of O-enriched acetic acid
17
by hydrolysis of acetic anhydride with O-enriched
water
Heidi M. Hultman,1,2 Kristina Djanashvili1 and Joop A. Peters1∗
1
Delft University of Technology, Applied Organic Chemistry and Catalysis, Julianalaan 136, 2628 BL Delft, The Netherlands
Delft University of Technology, Biocatalysis and Organic Chemistry, Julianalaan 136, 2628 BL Delft, The Netherlands
2
Received 4 April 2003; Revised 26 June 2003; Accepted 30 June 2003
17O-enriched acetic acid (2.5% in 17O) was synthesized by hydrolysis of acetic anhydride with 17O-enriched
water. The reaction was monitored by 17O and 1H NMR spectroscopy. Acetic anhydride, 17O-enriched
in both the ether and the carbonyl oxygens, was observed as an intermediate. This can be ascribed to
competition between acetic acid and water for nucleophilic attack on acetic anhydride. Copyright  2003
John Wiley & Sons, Ltd.
KEYWORDS: NMR; 17O NMR; 1H NMR; labelling; hydrolysis; acetic acid; acetic anhydride; water
was studied further by 17O and 1H NMR spectroscopy using
acetonitrile as the solvent. This solvent was selected because
of its miscibility with water.
INTRODUCTION
The natural abundance of 17O is only 0.037%. A large
quadrupole interaction (spin number I D 5/2, Q D ꢀ2.6 ð
10ꢀ30 m2)1 causes efficient relaxation and, consequently,
broadening of 17O NMR resonances, particularly of com-
pounds with high molecular weights.2 Therefore, 17O enrich-
ment is often desirable to obtain 17O NMR spectra within a
reasonable time.
A variety of methods are known for the preparation of
17O-enriched compounds. Starting compounds include 17O-
enriched oxygen, water and carbon monoxide. For example,
the oxygens of carboxylic acids may be isotopically labelled
via saponification of the corresponding esters with labelled
NaOH in methanol or by acid-catalysed O-exchange of the
free acid in labelled water.3
Acetic anhydride can be readily converted into acetic
acid by hydrolysis.4 This reaction is very clean; no side
products are formed. Therefore, it is ideal for the preparation
of 17O-enriched acetic acid. In our recent ligand-exchange
studies on dirhodium catalysts,5 we employed 17O-enriched
acetic acid. During the preparation of this compound by
the hydrolysis of acetic anhydride with a stoichiometric
amount of H217O in CDCl3, we observed some unexpected
results. In the reaction where the 17O-enriched acetic acid was
needed, CDCl3 was the solvent. Therefore, CDCl3 was also
used as a solvent during the preparation of the 17O-enriched
acetic acid. Because of the unexpected results that were
observed in the initial experiments, the hydrolysis reaction
EXPERIMENTAL
Materials
Acetic anhydride and pyridine were obtained from Aldrich,
deuterated acetonitrile from Cambridge Isotope Laboratories
and 17O-enriched water (10% 17O) from Cortec (Paris, France).
Hydrolysis of acetic anhydride
Acetic anhydride (0.0261 g, 0.256 mmol) was weighed into
an NMR tube. Deuterated acetonitrile (0.7457 g) and 17O-
enriched water (46 µl, 2.56 mmol, 10% 17O) were added and,
after shaking the mixture, the tube was placed immediately
°
in the NMR machine, which was maintained at 50 C. The
reaction was followed in time during 5 days by measuring
17O and 1H NMR spectra.
Hydrolysis of acetic anhydride in the presence of
pyridine
Acetic anhydride (0.0221 g, 0.217 mmol) and pyridine
(0.0183 g, 0.0231 mmol) were weighed into an NMR tube.
Deuterated acetonitrile (0.7007 g) and 17O-enriched water
(39 µl, 2.17 mmol, 10% 17O) were added and, after shaking
the mixture, the tube was placed immediately in the NMR
°
machine, which was maintained at 50 C. The reaction was
ŁCorrespondence to: Joop A. Peters, Delft University of Technology,
Applied Organic Chemistry and Catalysis, Julianalaan 136, 2628 BL
Delft, The Netherlands. E-mail: j.a.peters@tnw.tudelft.nl
followed in time during 3 days by measuring 17O and 1H
NMR spectra.
Copyright  2003 John Wiley & Sons, Ltd.

960
H. M. Hultman, K. Djanashvili and J. A. Peters
NMR spectroscopy
1H (300 MHz) and 17O (40 MHz) NMR spectra were recorded
°
on a Varian Inova-300 spectrometer at 50 C using 5 mm
sample tubes. Chemical shifts are reported as υ values.
17O NMR experiments were performed using water as an
external reference. Typically, 3000 scans were collected using
a sweep width of 29 996 Hz and an acquisition delay of 0 s.
The peak positions and intensities of the 17O resonances were
determined by fitting the observed signals with Lorentzian
line functions.
RESULTS AND DISCUSSION
Upon addition of a small amount of 10% 17O-enriched
water to a sample of acetic anhydride in acetonitrile, with
pyridine as a catalyst,6,7 initially only the water resonance
was observable in the 17O NMR spectrum. After about
5 min, three new signals (at 270, 274 and 415 ppm) became
observable (Fig. 1). The resonance at 274 ppm can be assigned
to the 17O nuclei in acetic acid, whereas the resonances at 270
and 415 ppm are due to 17O labelling of the acetic anhydride.
The 17O labelling of the oxygen nuclei in acetic anhydride
can be rationalized by nucleophilic attack of the initially
formed 17O-enriched acetic acid on the residual starting
compound acetic anhydride (see Scheme 1). This reaction is
similar to the well known synthesis of mixed anhydrides by
reaction of a carboxylic acid with acetic anhydride.8
Figure 2. Relative intensities of the 17O NMR signals of acetic
acid (ꢀ) and acetic anhydride (C O, ; C—O—C, ) in the
ꢁ
ž
reaction mixture of the pyridine-catalysed hydrolysis of acetic
anhydride with 10% 17O-enriched water in acetonitrile.
Scheme 1. Reactions that play a role in the 17O-exchange
reaction between acetic anhydride, acetic acid and water.
Figure 3. Concentrations of acetic acid ( ) and acetic
ž
The relative intensities of the various 17O resonances as a
function of time are displayed in Fig. 2. The concentrations
of acetic anhydride and acetic acid in the reaction mixture
anhydride ( ) in the reaction mixture of the pyridine-catalysed
ꢁ
hydrolysis of acetic anhydride with 10% 17O-enriched water in
acetonitrile as determined by 1H NMR.
were determined by integration of the observed resonances
in the corresponding 1H NMR spectra (see Fig. 3).
From the concentrations of the species as obtained from
1H NMR and from the relative 17O intensities (see Fig. 2),
the percentages of 17O in acetic acid and acetic anhydride as
a function of time were calculated. These data are depicted
in Fig. 4, which shows that at each time, the extents of 17O
labelling in acetic acid and acetic anhydride are the same.
Apparently, the rate of reaction between acetic acid and
acetic anhydride is much faster than that between water
and acetic anhydride, which can be explained by the higher
nucleophilicity of acetic acid compared with water.
The reaction was also carried out without pyridine, giving
similar results. However, the hydrolysis was significantly
slower in this case. With pyridine the reaction was finished
within 2 days, whereas it took 5 days in its absence.
It can be concluded that 17O NMR reveals a side reaction
that escapes observation by other techniques.9
Figure 1. 17O NMR spectrum of the reaction mixture of the
pyridine-catalysed hydrolysis of acetic anhydride with 10%
17O-enriched water in acetonitrile after 160 min of reaction. For
conditions, see Experimental.
Copyright  2003 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2003; 41: 959–961

Hydrolysis of acetic anhydride with 17O-enriched water
961
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Figure 4. Percentage of 17O in acetic acid ( ) and acetic
ž
anhydride ( ) in the reaction mixture of the pyridine-catalysed
ꢁ
hydrolysis of acetic anhydride with 10% 17O-enriched water in
acetonitrile (determined by 17O and 1H NMR).
Copyright  2003 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2003; 41: 959–961