Substituent effects on15N and13C NMR chemical shifts of 5-phenyl-1,3,4-oxathiazol-2-ones: A theoretical and spectroscopic study

Article abstract of DOI:10.1002/mrc.2082

The synthesis and assignment of ¹⁵N and ¹³C NMR signals of the 1,3,4-oxathiazol-2-one ring in a series of para-substituted 5-phenyl derivatives are reported. DFT calculations of ¹⁵N and ¹³C chemical shifts correspond closely to observed values. Substituent effects are interpreted in terms of the Hammett correlation and calculated bond orders. Copyright

Full text of DOI:10.1002/mrc.2082

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2007; 45: 985–988
Published online 26 September 2007 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/mrc.2082
Note
Substituent effects on 15N and 13C NMR chemical shifts
of 5-phenyl-1,3,4-oxathiazol-2-ones: a theoretical and
spectroscopic study
J. Hodge Markgraf,1† Lu Hong,1 David P. Richardson1∗ and Mark H. Schofield2∗
1
Department of Chemistry, Williams College, Williamstown, MA 01267-2692, USA
Department of Chemistry, Haverford College, Haverford, PA 19041-1392, USA
2
Received 22 February 2007; Revised 10 August 2007; Accepted 13 August 2007
The synthesis and assignment of 15N and 13C NMR signals of the 1,3,4-oxathiazol-2-one ring in a series
of para-substituted 5-phenyl derivatives are reported. DFT calculations of 15N and 13C chemical shifts
correspond closely to observed values. Substituent effects are interpreted in terms of the Hammett
correlation and calculated bond orders. Copyright  2007 John Wiley & Sons, Ltd.
KEYWORDS: 13C NMR; 15N NMR; chemical shifts; DFT calculations; electronic effects; Hammett correlation;
5-phenyl-1,3,4-oxathiazol-2-ones
in this table. The calculated and experimental 15N shifts fit
the relation,
INTRODUCTION
The transmission of substituent effects in selected azole
systems has been studied by a combination of 15N NMR
and 13C chemical shift data for 3-phenylisoxazoles1 and
2-phenyl-1,3,4-oxadiazoles.2 Hammett correlations estab-
lished the nature of electronic delocalization, and density
functional theory calculations predicted chemical shifts and
heterocyclic ring bond orders. We report, herein, the appli-
cation of these methods to 5-phenyl-1,3,4-oxathiazol-2-ones
(1a–1h), for which substituent effects have not previously
been assessed. These compounds are used in antimicrobial,
herbicidal, and polymer cross-linking applications,3 and they
are the precursors of choice for the generation of benzonitrile
N-sulfides.4 The synthesis of the desired series was carried
out by a standard procedure (Scheme 1).5
υcalcd D ꢁ1.28 š 0.03ꢂυexpt C ꢁ52.3 š 4.1ꢂ
N D 8, R2 D 0.999
ꢁ1ꢂ
Consistent with our previous studies of substituted 3-
phenylisoxazoles,1 the range of chemical shifts is fairly
narrow (calculated: 22.2 ppm; experimental: 17.1 ppm) and
the trend in shifts is consistent with the electron-releasing or
electron-withdrawing ability of the phenyl para substituent
(Y). In keeping with expected electronic effects, electron-
withdrawing groups cause 15N signals to appear more
deshielded (i.e. less negative values, since CH3NO2 is the
chemical shift reference) while electron-releasing groups
cause 15N signals to appear more shielded. Also consistent
with our earlier work, the calculated chemical shifts are
regularly higher than the experimental values (υave.
D
RESULTS AND DISCUSSION
15N NMR chemical shift analysis
7.28) but their variation is small (υst.dev D 1.51). In
accordance with the work of Cheeseman et al.,7 this small
systematic deviation derives from the calculated chemical
shift of the reference compound (CH3NO2), but does not
compromise the excellent correlation between theory and
experiment. Likewise, the calculated natural charge of
the 1,3,4-oxathiazol-2-one ring nitrogen (N-4) is entirely
consistent with the increasing electron-donating ability of the
Y group and mirrors the observed (and calculated) chemical
shifts nicely.
The calculated and experimentally determined 15N chemical
shifts for compounds 1a–1h are listed in Table 1, arranged
according to ꢀp values.6 A set of calculated chemical
shifts, determined for geometry-optimized compounds, and
referenced to the calculated chemical shift of CH3NO2 (see
experimental section for complete details) are also included
ŁCorrespondence to: David P. Richardson, Department of
Chemistry, Williams College, 47 Lab Campus Drive, Williamstown,
MA 01267-2692, USA. E-mail: david.p.richardson@williams.edu.
Mark H. Schofield, Department of Chemistry, Haverford College,
370 Lancaster Avenue, Haverford, PA 19041-1392, USA.
E-mail: mschofie@haverford.edu
The 15N chemical shifts in Table 1 also display the
expected response to ꢀp Hammett values and fit the relation,
υexpt. D ꢁ14.48 š 1.22ꢂꢃ ꢀ ꢁ162.02 š 0.45ꢂ
†In memoriam; deceased 11 January 2007.
N D 8, R2 D 0.97
ꢁ2ꢂ
Copyright  2007 John Wiley & Sons, Ltd.

986
J. H. Markgraf et al.
Table 2. Experimental and calculated 13C NMR chemical shift
(υ) data and Hammett substituent constants of C-2 and C-5 for
5-phenyl-1,3,4-oxathiazol-2-ones 1a–1h
The strongly positive ꢃ value is entirely consistent with
our observation that 15N chemical shifts are highly sensitive
to the electronic nature of the Y group.8
These results are congruent with our results for
3-phenylisoxazoles,1 while also showing some important
differences. In the 3-phenylisoxazoles, the polarizing effects
of the Y group are attenuated by the isoxazole ring oxygen,
resulting in a smaller range of 15N chemical shifts (9.0 ppm)
than in the 5-phenyl-1,3,4-oxathiazol-2-ones (17.1 ppm). We
attribute this to an increase in the N–O bond order in
the 3-phenylisoxazoles as supported by Wiberg bond index
calculations.1
C-2
Calcdb
C-5
Calcdb
a
Compd.
Y
ꢀp
Expt.c
Expt.c
1a
1b
1c
1d
1e
1f
OMe ꢀ0.27
164.03
164.40
164.30
163.27
163.51
163.45
163.25
162.85
157.23
157.49
157.36
156.39
156.41
156.55
156.01
155.33
181.74
181.50
181.27
181.08
180.98
180.90
180.50
180.06
174.13
173.94
173.80
173.59
173.40
173.40
173.03
172.60
Me
H
F
Cl
Br
ꢀ0.17
0.00
0.06
0.23
0.23
0.54
0.78
1g
1h
CF3
NO2
13C NMR chemical shift analysis
The data presented in Table 2 for the corresponding 13C
chemical shifts of compounds 1a–1h indicate that, once
again, the calculated and experimental ranges of chemical
shifts agreed closely. Although the range of 13C shifts
observed is small, the correlation between the measured
chemical shifts and the Hammett ꢀp constants for phenyl
para substituents is good (R2: C-2, 0.87) or excellent
(R2: C-5, 0.99), with electron-withdrawing substituents
causing increased deshielding at both C-2 and C-5, as
expected. However, as with the 1,3,4-oxathiazol-2-one ring
nitrogen, C-2 and C-5 are more strongly affected by the Y
a Ref. 6.
b B3LYP/6-311CCg(2d,2p); relative to calculated tetramethyl-
silane D 183.37 ppm.
c relative to CDCl3 D 77.00 ppm.
Y
O
1O
5
ClCOSCl
100oC, toluene
2
Y
C
NH2
N4
O
3S
Table 1. Experimental and calculated 15N NMR chemical shift
(υ) data, Hammett substituent constants, and natural atomic
charges of N-4 for 5-phenyl-1,3,4-oxathiazol-2-ones 1a–1h
1a
1b 1c 1d 1e 1f 1g
1h
Y
OMe Me
H
F
Cl Br CF3 NO2
Scheme 1. Synthesis of 5-phenyl-1,3,4-oxathiazol-2-ones
(1a–1h).
Natural
charge
a
Compd.
Y
ꢀp
Calcd.b
Expt.c
1a
1b
1c
1d
1e
1f
Ome
Me
H
F
Cl
Br
CF3
NO2
ꢀ0.27
ꢀ0.17
0.00
0.06
0.23
0.23
0.54
0.78
ꢀ162.53
ꢀ156.22
ꢀ153.17
ꢀ155.22
ꢀ152.35
ꢀ152.00
ꢀ145.93
ꢀ140.37
ꢀ167.46
ꢀ162.90
ꢀ160.67
ꢀ161.69
ꢀ159.38
ꢀ159.02
ꢀ154.49
ꢀ150.39
ꢀ0.645
ꢀ0.637
ꢀ0.633
ꢀ0.636
ꢀ0.633
ꢀ0.632
ꢀ0.626
ꢀ0.621
group. In an attempt to understand some of these trends, we
performed Wiberg bond index calculations (Table 3).
Several interesting features emerge. First, there is a
significant bonding interaction between C-2 and S-3 (greater
than O-1/C-2) that is consistent with the participation
of the sulfur lone pair in the 2-one carbonyl ꢄ system,
producing an aromatic system (as shown in resonance
structure II, Fig. 1). As the Y group becomes increasingly
electron-withdrawing, the electron density at sulfur moves
toward nitrogen, leading to a slight increase in the S-3/N-4
bond order, a slight decrease in the C-2/S-3 bond order,
and a concomitant increase in the C-2/O-6 bonding in the
1g
1h
a Ref. 6.
b B3LYP/6-311CCg(2d,2p); relative to calculated CH3NO2
D
ꢀ153.31 ppm.
c Relative to CH3NO2 D 0.00 ppm.
Table 3. Calculated Wiberg bond orders of 5-phenyl-1,3,4-oxathiazol-2-ones 1a–1h
a
Compd.
Y
ꢀp
O-1/C-2
C-2/S-3
S-3/N-4
N-4/C-5
C-5/O-1
C-2/O-6
C-5/C-10
1a
1b
1c
1d
1e
1f
OMe
Me
H
F
Cl
Br
CF3
NO2
ꢀ0.27
ꢀ0.17
0.00
0.06
0.23
0.23
0.54
0.78
0.926
0.922
0.921
0.920
0.916
0.916
0.916
0.914
1.094
1.093
1.091
1.090
1.091
1.090
1.090
1.087
1.008
1.009
1.011
1.013
1.011
1.013
1.013
1.015
1.670
1.684
1.692
1.695
1.693
1.694
1.694
1.698
0.962
0.971
0.973
0.975
0.976
0.977
0.977
0.980
1.762
1.770
1.772
1.775
1.777
1.778
1.779
1.783
1.091
1.071
1.064
1.060
1.062
1.061
1.060
1.055
1g
1h
a Ref. 6.
Copyright  2007 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2007; 45: 985–988
DOI: 10.1002/mrc

Substituent effects on 15N and 13C NMR chemical shifts of 5-phenyl-1,3,4-oxathiazol-2-ones
987
O–
O
O
O
N
O
N
O
N
Y–
Y
Y
S+
S+
S
I
II
III
Figure 1. Resonance effects in 5-phenyl-1,3,4-oxathiazol-2-ones.
solvent. 15N data were acquired at natural abundance. 15N
chemical shifts were measured directly using a standard
inverse gated decoupling pulse sequence (zgig), while 13C
chemical shifts were measured using a standard power gated
decoupling pulse sequence (zgpg30), both from the Bruker
pulse sequence library.
Spectral windows were set at 240 ppm for 13C and
500 ppm for 15N. For 15N acquisitions, a total of ca. 15 k scans
of 16 k data points were collected and then zero-filled to 32 k
points prior to Fourier transformation (FT). The recycle delay
(D1) was set at 5 s, and total acquisition time per sample was
ca. 21 h. 13C acquisitions collected a total of ca. 300 scans
of 32K data points and then zero-filled to 64K points prior
to FT. The recycle delay (D1) was set at 2 s. Chemical shift
measurement accuracy for all experiments was estimated at
š0.1 ppm.
carbonyl group (structure III). As the 1,3,4-oxathiazol-2-one
ring becomes increasingly electron-deficient, the remaining
ring bonds, N-4/C-5 and C-5/O-1, show a bond order
increase that is significant in magnitude.9 Although this
increase, particularly for N-4/C-5, is not what might be
expected from a simple resonance picture (Fig. 1), it is
consistent with an overall ring contraction arising from
a lowering (by induction) of the C-5 orbital energy,
thus enhancing the ꢄ character of the N-4/C-5 (and C-
5/O-1) bonds. Moreover, this pattern was observed in
our studies on 3-phenylisoxazoles.1 However, unlike the
3-phenylisoxazole ring, which attenuates both electron-
donating and -withdrawing substituents, the bond orders in
the 1,3,4-oxathiazol-2-one ring system change monotonically
over the range of Y groups we studied. For this reason, all of
the chemical shifts (15N and 13C) of the oxathiazol-2-one ring
system are more profoundly influenced by the nature of the
phenyl substituent.
Computational methods
All computations were carried out using the Gaussian 03
program10 andemployedtheB3LYPfunctional.11 Substituted
5-phenyl-1,3,4-oxathiazole geometries were optimized in the
gas phase using the very tight convergence criteria (the 6-
311CCg(2d,2p) basis set was used for all models) and with
an ultrafine integration grid. Frequency calculations were
performed to demonstrate that the structures represented the
minimum energy (no imaginary frequencies were observed).
15N and 13C chemical shifts were calculated using the GIAO
method12–15 and were referenced to the calculated chemical
shift of nitromethane (ꢀ153.31 ppm) or tetramethylsilane
(183.37) optimized at the same level of theory. Wiberg Bond
indices16 and Natural Population Analysis Charges17 were
calculated using NBO 3.1.18
EXPERIMENTAL
Melting points were determined on a MelTemp apparatus.
Extracts were dried over Na2SO4, and solvents were
removed by rotary evaporation at reduced pressure. Product
purities were determined by gas chromatography–mass
spectrometry analysis on a Hewlett Packard HP 6890
system equipped with a HP-5MS cross-linked diphenyl
(5%) dimethyl (95%) polysiloxane capillary column (30 m ð
0.25 mm ð 0.25 µm film), a 5973 mass selective detector, and
a HP Kayak XA computer.
Compounds
Preparation of 5-phenyl-1,3,4-oxathiazol-2-ones (1a–1h)
5-Phenyl-1,3,4-oxathiazol-2-ones were prepared by a stan-
dard procedure employing treatment of substituted ben-
zamides with chlorocarbonylsulfenyl chloride; compounds
1a–1h have been reported previously.5 They were purified by
recrystallization from an appropriate solvent; their physical
constants and spectral data matched literature values.
Acknowledgements
This work was supported by a Senior Scientist Mentor Initiative
Award from The Camille and Henry Dreyfus Foundation, Inc.
(Award SI-00-031 to J.H.M.). Computer resources provided by
Haverford College and the National Computer Science Alliance
(Grant CHE050033N to M.H.S.) are gratefully acknowledged.
Additional support was provided by the Williams College and
Haverford College Faculty Research Funds. We thank Deborah
Morandi for assistance with preparation of the manuscript.
NMR spectroscopy
NMR spectra were measured at 298 K with a Bruker Avance
DRX 500 MHz NMR spectrometer operating at frequencies
of 500.630 (1H), 125.884 (13C), and 50.748 (15N) using a
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DOI: 10.1002/mrc