17O NMR studies of substituted 1,3,4-oxadiazoles

Article abstract of DOI:10.1002/mrc.2804

Three series of substituted 1,3,4-oxadiazoles were studied by ¹⁷O NMR spectroscopy. Chemical shifts values were correlated with empirical Hammett parameters as well as calculated bond lengths and chemical shielding values.

Full text of DOI:10.1002/mrc.2804

Research Article
Received: 25 May 2011
Revised: 5 July 2011
Accepted: 9 July 2011
Published online in Wiley Online Library: 15 September 2011
(wileyonlinelibrary.com) DOI 10.1002/mrc.2804
17O NMR studies of substituted
1,3,4-oxadiazoles
∗
˙
Błazej Gierczyk, Maciej Zalas, Marcin Kaz´mierczak, Jakub Grajewski,
˙
Radosław Pankiewicz and Bozena Wyrzykiewicz
Three series of substituted 1,3,4-oxadiazoles were studied by 17O NMR spectroscopy. Chemical shifts values were correlated
c
with empirical Hammett parameters as well as calculated bond lengths and chemical shielding values. Copyright ꢀ 2011 John
Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: 17O; chemical shifts; 1,3,4-oxadiazoles; substituent effects; DFT calculations
Introduction
in vacuum and the semisolid residue was neutralized with 10%
aqueous Na2CO3. The crude 1,3,4-oxadiazole was purified by
crystallization from ethanol (yield >80%). The structures of the
compounds obtained are summarized in Fig. 1, and the synthetic
pathways were presented in Fig. 2.
The 1,3,4-oxadiazole chemistry has been dynamically developing
because of the importance of this class of compounds. They have
been widely studied as fluorophores in light-emitting devices,[1,2]
electrochromic materials,[3] organic semiconductors[4] or dyes
for dye-sensitized photovoltaic cells.[5] Also the pharmacological
properties of 1,3,4-oxadiazole unit containing compounds have
prompted intense studies of their derivatives.[6,7] As many
propertiesofthesemoleculesdependonthesubstituentcharacter,
much attention has been paid to the correlations between their
spectral parameters and structures.
In our previous papers, we have reported the 13C and 15N
NMR studies of 2-aryl-1,3,4-oxadiazoles[8] and substituted 2-
(phenylamino)-5-phenyl-1,3,4-oxadiazoles.[9] This paper presents
the results of a study of 17O chemical shifts of 2-aryl-1,3,4-
oxadiazoles, 2,5-diaryl-1,3,4-oxadiazoles and 2-(arylamino)-5-aryl-
1,3,4-oxadiazoles. The experimental results were correlated with
Hammett coefficients and calculated values of chemical shifts as
well as with bond lengths. To the best of our knowledge, no 17O
NMR data have been published for 1,3,4-oxadiazoles.
NMR measurements
The 17O NMR spectra were recorded at 298 K on a Bruker
AvanceDRX600spectrometeroperatingatfreque◦ ncy81.339 MHz,
equipped with 5-mm BBO probehead (BB/1H; 90 17O pulse width
5 µs) with a ring 2 sequence from Bruker pulse library and on
Varian Gemini 300 spectrometer, at 40.680 MHz with 10 mm direct
detection probehead (BB/1H; 90◦ 17O pulse width 17 µs) using
ordinary one-pulse sequence (s2pul). The acquisition parameters
were as follows (the values for Varian apparatus were given in
brackets): spectral width 30 kHz (12 kHz), acquisition time 20 ms,
90◦ flip angle (70◦; if 90◦ pulse was used some distortion of
reference signal has occurred). For the nitro group containing
compounds, the spectral width was set to 52 kHz (25 kHz). The
spectra were measured for 0.05–0.1 M solutions in CDCl3. External
H2O in a 1-mm diameter capillary inserted coaxially in NMR
tube was used as a reference (0.00 ppm). On Varian Gemini 300
spectrometer, spectra were recorded without lock to avoid the
disturbance of the signals by the deuterium frequency pulses;
in the case of the measurements on Bruker Avance apparatus,
deuterium lock was used. On Bruker spectrometer 10 000–50 000
transients, while on Varian one, 50 000–200 000 transients were
accumulated to obtain satisfactory S/N ratio. Line broadening
factor of 10–50 Hz was used. The chemical shifts accuracy of
17O NMR shifts of oxadiazole ring oxygen atoms was better than
0.1 ppm, while for NO2 and MeO groups it was only 0.5 ppm,
because of the strong 17O resonance line broadening observed
for the oxygen atoms of these functional groups.
Experimental
Synthesis
The syntheses of 2-aryl-1,3,4-oxadiazoles and 2-(arylamino)-5-
aryl-1,3,4-oxadiazoles were made according to the procedures
described previously.[8–10] The 2,5-diaryl-1,3,4-oxadiazoles were
obtained from the corresponding N, Nꢁ-diaryloylhydrazides as
follows.
To a solution of N-aryloylhydrazide (0.01 mol) in dry pyridine
(10 cm3), 0.011 mol of aryloyl chloride was added dropwise over
30 min, and the mixture was heated on water bath for over 1 h.
Then the solvent was evaporated, and the residue obtained was
crystallized from ethanol to obtain pure N, Nꢁ-diaryloylhydrazides
(yield >90%). The synthesized N, Nꢁ-diaryloylhydrazides (0.01 mol)
were heated under reflux with phosphorous oxychloride (10 ml)
for 10 h. After this time, the excess of the POCl3 was removed
∗
Correspondence to: Błaz˙ej Gierczyk, Faculty of Chemistry, A. Mickiewicz Univer-
´
sity, Grunwaldzka 6, 60-780 Poznan, Poland. E-mail: hanuman@amu.edu.pl
´
Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan,
Poland
c
Magn. Reson. Chem. 2011, 49, 648–654
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

17O NMR studies of substituted 1,3,4-oxadiazoles
Figure 1. General structures of the substituted 1,3,4-oxadiazoles studied.
Figure 2. Synthesis of the compounds studied.
Theoretical calculations
Mulliken and NBO charges, as well as computed geometries (as
Cartesian coordinates) were given in the Supporting Information.
Starting structures were preoptimized by the PM3 semiempirical
method. Conformational search was performed by examining all
torsion angles along acyclic bonds using CAChe 5.0. Except for the
methoxy substituted compounds, one conformer was found in the
range of 4 kcal/mol. The pre-optimized input structures were then
fully optimized by the DFT method at the B3LYP/6-311G∗∗ (2d,
2p) level of theory with Gaussian03.[11] Molecules were allowed
to relax concurrently and without any enforcement of symmetry
restrictions. The optimized structures were used for calculations
of NMR shifts. These calculations were also performed using DFT,
at the same level of theory, which provided a good correlation
with experimental results. For OMe analogues, two conformers
were found to have similar energies. They differ in the value
of the H3C-O-C4ꢁ -C3ꢁ dihedral angle – for one conformer it is 0◦,
for the other −180◦. The 17O NMR parameters as well as bond
lengths and Mulliken charges in oxadiazole ring were calculated
forbothconformations, butthedifferencesinthesevaluesforboth
conformers were insignificant. Because the iodine atom was not
parameterized in this calculation basis set, the computed spectral
and molecular parameters for iodo-substituted oxadiazoles were
not presented. The biphenyl derivatives (1g, 2g, 3e and 4f)
have stacked in fluctuations during geometry optimization. The
spectral data, obtained after computation force stopping, did
not correlate with the other results and were also excluded
from comparisons. The PCM calculations of NMR parameters
were made for compounds of series 1. Two approaches were
applied:(i) calculationofthechemicalshiftwithPCMforgas-phase
optimizedstructuresand(ii)bothgeometryoptimizationandNMR
calculations with PCM. The calculated values of bond lengths,
Results and Discussion
17O NMR chemical shifts of oxygen atom of 2-aryl and 2,
5-diaryl-1,3,4-oxadiazoles
The half-widths of the signals were 80–100 Hz for heterocyclic,
350–450 Hz for MeO and 700–900 Hz for NO2 oxygen atoms;
therefore, the δ 17O data were given to 0.01 ppm for the first
one, whereas to 0.1 ppm for the others. The observed values
of the 17O NMR chemical shifts are summarized in Table 1. For
monosubstituted 1,3,4-oxadiazoles, they are included between
259.44 (1b) and 264.61 ppm (1m) and clearly depend on the
electronic character of the substituent. The electron-withdrawing
groups cause deshielding, while the electron-donating ones, the
shielding. The range of the δ 17O NMR values is 5.17 ppm. Similar
tendencies were observed for diaryl substituted oxadiazoles. The
smallest value of 17O chemical shift was measured for compound
3a (251.28 ppm), whereas the highest one for 4k (255.89 ppm).
The ranges of the chemical shifts for a series of compounds 2, 3
and 4 are 3.20, 2.21 and 4.13 ppm, respectively. The δ 17O values
for 2-aryl-1,3,4-oxadiazoles are about 10 ppm higher than that
observed for 2,5-diaryl-1,3,4-oxadiazoles.
The long-range substituent effects on the 17O NMR chemical
shifts observed are surprisingly small and lower than expected
in the extended π electron systems. They were about one-fifth
of those detected for nitrogen atoms of oxadiazole ring.[8,9] This
is a good experimental proof of the low aromaticity or even
non-aromatic character of 1,3,4-oxadiazoles, postulated by some
c
Magn. Reson. Chem. 2011, 49, 648–654
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

B. Gierczyk et al.
Table 1. Experimental and calculated 17O NMR chemical shifts and CA –O bond lengths for the compounds studied
Experimental 17O NMR chemical
shifts (ppm)
Calculated 17O NMR chemical
shifts (ppm)
´
Comp.
R
Rꢁ
O-1
OCH3
NO2
O-1
OCH3
NO2
CA –O bond lengtha (Å)
1a
1b
1c
1d
1e
1f
H
–
–
263.21
259.44
260.72
261.44
262.28
263.45
262.37
262.94
263.05
262.84
262.80
264.44
264.61
253.15
251.58
252.04
252.75
252.73
254.03
253.20
253.17
253.62
253.36
253.44
254.39
254.78
251.28
251.48
252.03
252.26
253.30
252.17
252.85
252.89
252.81
252.52
253.31
252.49
251.76
252.40
253.84
255.37
254.55
254.08
254.42
254.68
254.27
255.29
255.89
236.24
235.96
235.80
236.04
236.41
236.62
–
–
–
311.98
306.91
307.57
309.11
310.98
313.71
–
–
–
1.3677
1.3702
1.3694
1.3685
1.3682
1.3662
–
N(CH3)2
NH2
OCH3
CH3
CF3
Ph
–
–
–
–
–
–
–
–
–
56.9
–
–
112.91
–
–
–
–
–
–
–
–
–
–
1g
1h
1i
–
–
–
–
–
F
–
–
–
311.31
311.91
311.98
–
–
–
1.3670
1.3670
1.3670
–
Cl
–
–
–
–
–
1j
Br
–
–
–
–
–
1k
1l
I
–
–
–
–
–
CN
–
–
–
314.03
315.20
299.16
294.75
295.35
296.72
298.17
299.56
–
–
–
1.3659
1.3657
1.3652
1.3672
1.3665
1.3658; 1.3664
1.3656
1.3641
–
1m
2a
2b
2c
2d
2e
2f
NO2
H
–
–
581.6
–
635.5
H
–
–
–
–
N(CH3)2
NH2
OCH3
CH3
CF3
Ph
H
–
–
–
–
H
–
–
–
–
H
56.2
–
–
111.84
–
H
–
–
–
H
–
–
–
–
2g
2h
2i
H
–
–
–
–
F
H
–
–
298.34
298.36
298.35
–
–
–
1.3646
1.3646
1.3646
–
Cl
H
–
–
–
–
2j
Br
H
–
–
–
–
2k
2l
I
H
–
–
–
–
CN
H
–
–
299.72
300.50
293.66
293.98
295.45
296.53
297.68
–
–
–
1.3639
1.3638; 1.3650
1.3683
1.3676
1.3669
1.3668
1.3653
–
2m
3a
3b
3c
3d
3e
3f
NO2
N(CH3)2
NH2
OCH3
CH3
CF3
Ph
H
–
580.3
–
634.04
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
H
54.8
54.8
55.2
55.7
56.4
56.0
55.9
56.3
56.0
55.7
56.6
57.4
–
–
109.54
–
–
109.94
–
–
110.64
–
–
–
111.19
–
114.02
–
–
–
–
3g
3h
3i
F
–
296.53
296.56
296.44
–
112.18
–
1.3658
1.3658
1.3658
–
Cl
–
112.63
–
Br
–
113.00
–
3j
I
–
–
–
3k
3l
CN
–
297.48
298.21
295.03
295.44
299.46
301.44
–
114.58
–
632.97
631.42
632.18
633.53
635.55
–
1.3652
1.3651; 1.3655
1.3669
1.3662
1.3653
1.3639
–
NO2
N(CH3)2
NH2
CH3
CF3
Ph
579.8
579.5
579.1
580.3
581.1
580.1
580.0
580.5
580.9
580.6
581.4
581.6
–
115.35
4a
4b
4c
4d
4e
4f
–
–
–
–
–
–
–
–
–
F
–
299.36
299.26
299.47
–
–
634.29
634.65
634.66
–
1.3644
1.3644
1.3644
–
4g
4h
4i
Cl
–
–
Br
–
–
I
–
–
4j
CN
–
301.26
301.76
282.57
280.86
280.92
281.37
282.22
282.08
–
636.02
636.45
–
1.3637
1.3636
1.3817; 1.3603
1.3838
1.3830
1.3824
1.3821
1.3803
4k
5a
5b
5c
5d
5e
5f
NO2
H
–
–
–
–
N(CH3)2
NH2
OCH3
CH3
CF3
H
–
–
–
–
H
–
–
–
–
H
54.3
–
–
110.89
–
H
–
–
–
–
H
–
–
–
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 648–654

17O NMR studies of substituted 1,3,4-oxadiazoles
Table 1. (Continued)
Experimental 17O NMR chemical
Calculated 17O NMR chemical
shifts (ppm)
shifts (ppm)
´
Comp.
R
Rꢁ
O-1
OCH3
NO2
O-1
OCH3
NO2
CA –O bond lengtha (Å)
5g
5h
5i
F
H
H
236.05
236.70
236.63
236.65
236.85
236.93
234.75
234.45
235.63
235.89
238.00
237.19
237.65
237.06
237.08
238.12
238.84
–
–
–
281.89
282.27
281.36
–
–
–
1.3809
1.3808
1.3809
–
Cl
Br
I
–
–
–
H
–
–
–
–
5j
H
–
–
–
–
5k
5l
CN
NO2
H
H
–
–
281.57
282.02
279.42
279.32
280.78
281.73
284.03
281.57
284.63
282.80
–
–
–
1.3802
1.3800
1.3622
1.3619
1.3609
1.3607
1.3582
1.3594
1.3591
1.3590
–
H
–
588.2
–
642.62
6a
6b
6c
6d
6e
6f
N(CH3)2
NH2
OCH3
CH3
CF3
F
–
–
–
–
H
–
–
–
–
H
45.7
–
–
98.20
–
H
–
–
–
–
–
–
–
–
–
–
H
–
–
–
H
–
–
–
6g
6h
6i
H
Cl
–
–
–
H
Br
–
–
–
–
H
I
–
–
–
6j
H
CN
NO2
–
–
284.63
285.22
1.3576
1.3571
6k
H
–
570.7
623.40
a Normal font: C2 –O; italic: C5 –O.
authors on the basis of theoretical calculations and structural
The experimental chemical shifts of the oxygen atoms correlate
data.[12,13] The aromaticity indices published for unsubstituted with global (σp) or inductive (σI) and resonance (σR) Hammett
1,3,4-oxadiazole were 23.6–25.3 (benzene: 100; furan: 28.3–32.2; parameters[15] of the substituents in the aryl ring. The equations
pyrole: 70.9–73.0).[13] Moreover, the substitution of oxadiazole of correlation for single global and two inductive and resonance
ring causes the decreasing of these indices values.[12] According parameters, respectively, areasfollows: δexp 17O = ρσp+ intercept
to Krygowski and Cyran´ski,[14] the heterocycles containing oxygen and δexp 17O = ρIσI + ρRσR+ intercept. The results of statistical
atom are less aromatic than analogous nitrogen or sulfur analysis of the correlation between 17O chemical shifts and
compounds because of the high electronegativity of oxygen. Hammett constants are collected in Table 2. As follows from the
It prevents the interaction of lone electron pair of O atom with presented results, for all groups of the compounds a satisfactory
π-electron system of double bonds. In consequence, the lone correlation of the experimental 17O chemical shift value and the
electron pairs of the oxygen atom do not contribute to the global Hammett parameter (r2 = 0.90–0.97) was obtained. The
delocalized electron system of the compounds studied. The π highest susceptibility constant (ρ) characterizes series 1, whereas
electrons of the aryl substituents are coupled only with C
N
the smallest series 3. It is in accordance with the chemical shifts
electrons, which causes higher sensitivity of 15N chemical shift to ranges discussed above. The Hammett analysis of separated
the substituent character. The shifts observed for oxygen atoms inductiveandresonancecoefficientsshowsdifferentcontributions
must have therefore mainly inductive origin.
of both effects for series 2 and 3 compounds (ρR and ρI values
The variation of the δ 17O values is less pronounced for are similar) in comparison with the analogous contributions for
disubstituted compounds (2–4) than for monosubstituted (1) other ones, for which the ρI values are higher then ρR. This
ones. For disubstituted oxadiazoles, the changes in the electron result supports the earlier discussed mechanisms of the long-
density of the heterocyclic ring atoms are smaller because of the range substituent effects on the 17O chemical shifts. The high
transfer of the electronic effects from the substituent (R) in first aryl contribution of inductive effects for compounds 1 and 4 is in
group (Ar1) via –C N–N C–bonds to the second aryl ring (Ar2). contrast to the contribution of both mechanisms to 15N chemical
If the Ar2 contains an electron-withdrawing substituent (e.g. NO2), shifts. In previous work, we have shown that the δ 15N values
the changes in R (in Ar1) cause more significant variation in the are much more influenced by the resonance interactions (the
electronic densities in all parts of the molecule. Therefore, the 17
O
ρR parameters are about twice higher than the ρI ones).[8] This
chemical shifts range is higher for oxadiazoles 4 than for phenyl confirms the low aromaticity of the 1,3,4-oxadiazole ring and a low
(series 2) or compounds containing (in Ar2) electron-donating coupling of oxygen atom lone electron pairs with the delocalized
group (3). It could be concluded that the electron-donating group electron system, formed by phenyl ring and C N π-electrons.
(e.g. MeO) in Ar2 stops the transfer of information about the
The comparison of the chemical shifts range of the compounds
substituentcharacterinAr1 anddecreasesthedelocalizationofthe studied with the data reported for the others groups of molecules,
π electrons in the molecule. Therefore, the less effective coupling containing the oxygen atom in the β-position to the aryl
of Ar1 ring electrons with C N ones causes a stronger interaction substituent, proves the thesis of the non- (or low) aromatic
with a lone electron pair of the oxygen atom. In consequence, the character of the oxadiazoles. The chemical shifts range for the
contribution of resonance effects in the 17O NMR chemical shifts systems with the oxygen coupled, via the C O double bond, with
should be the highest for series 3 and the smallest for 4.
the π-electrons of the aryl rings is about ten times larger than for
c
Magn. Reson. Chem. 2011, 49, 648–654
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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B. Gierczyk et al.
Table 2. Statistical data for correlation analysis between the 17O NMR chemical shifts of the 1,3,4-oxadiazole ring oxygen atom and Hammett
constants, calculated chemical shifts as well as CA –O bond length for the compounds studied
Compounds
Parameter
ρ
sρ
i
si
n
R2
1a–1m
σp
2.96 0.21
σI: 3.46 0.26
σR: 1.92 0.43
0.59 0.04
−1066 78
1.82 0.09
σI: 1.82 0.14
σR: 1.80 0.24
0.49 0.05
−833 79
262.44 0.01
262.88 0.18
13
13
0.94
0.97
σI and σR
δcalc
LC–O
78 11
1720 110
253 0.04
253 0.18
11a
11a
13
0.97
0.95
0.97
0.95
2a–2m
σp
σI and σR
13
δcalc
LC–O
105 18
1390 109
11a
11a
13
0.88
0.92
0.95
0.91
3a–3l and 2d
4a–4k, 2m and 3l
5a–5l
σp
1.41 0.09
σI: 1.38 0.14
σR: 1.48 0.24
0.51 0.04
−698 29
252.45 0.04
252.43 0.10
σI and σR
13
δcalc
LC–O
102 13
1207 40
11a
11a
13
0.93
0.98
0.93
0.95
σp
2.36 0.20
σI: 2.92 0.18
σR: 1.20 0.31
0.51 0.03
−1148 113
0.69 0.11
σI: 0.68 0.17
σR: 0.69 0.30
–
254.08 0.09
254.57 0.13
σI and σR
13
δcalc
LC–O
102
9
11a
11a
12
0.97
0.92
0.80
0.80
1821 154
236.36 0.05
236.36 0.13
σp
σI and σR
12
δcalc
LC–O
–
11a
11a
12
No correlation
No correlation
0.95
–
–
6a–6k and 5a
σp
2.7 0.19
236.57 0.09
236.18 0.18
σI and σR
σI: 2.28 0.24
σR: 3.60 0.42
0.70 0.08
−837 49
12
0.97
δcalc
40 11
11a
11a
0.84
0.97
LC–O
1375 67
a Compounds with iodine and phenyl substituents were omitted.
1,3,4-oxadiazoles studied, e.g. for four-substituted acetophenones
δ
single Csp2-NH bond[18]) and disturbance in the oxadiazole ring
geometry. The C2 –O bond length increases by about 0.02–0.03 Å
in comparison with the typical values of oxadiazoles. The strong
electron-donating iminoaryl group (NH-Ar2) in compounds 5 and
6 is responsible for a weak π-electron delocalization and coupling
betweentheAr1 substituentandtheheterocyclicring. Thisineffec-
tive delocalization causes the lowest variation in the 17O chemical
shift values of oxadiazoles belonging to series 5, in comparison
with those for the other systems studied (δδ 17O = 1.1 ppm). The
effects observed for compounds 6 are much more pronounced.
The difference between the extreme values of the 17O chemi-
cal shift in this series is about 4 ppm. It could be explained as
the effect of the interaction between the lone pair of the NH
nitrogen atom with the heterocyclic ring electron system. The
values of Mulliken charges of NH atom as well as C5 –NH bond
lengths are significantly affected by the changes in Ar2 substituent
17O (p-NO2) = 564 ppm while δ 17O (p-NH2) = 514 ppm.[16] Also
the molecules with non-coupled electron systems show higher
variation of the oxygen chemical shifts. For para substituted
benzyl alcohols and benzyl acetates, the differences between the
limit values (for nitro- and dimethylamino- derivatives) are 14.0
and 13.0 ppm, respectively.[17]
17O NMR chemical shifts of oxygen atom of 2-arylamino-5-
aryl-1,3,4-oxadiazoles
The oxygen-17 signals observed for NH-substituted 1,3,4-
oxadiazole rings are by about 20 ppm upfield shifted than that
for mono- or diarylsubstituted ones, which is a consequence
of decreasing aromaticity of these compounds and increasing
length of the C2 –O bond. This stay in accordance with the
theoretical calculations of arylamino-1,3,4-oxadiazoles aromatic-
ity. The HOMA indices published for phenylamino substituted
1,3,4-oxadiazoles are about one-third to one-fifth of that for aryl
substituted ones.[12] In consequence, these compounds may be
recognized as non-aromatic. As follows from the geometry calcu-
lation of derivatives 5 and 6, the lone pair of the NH nitrogen atom
interacts with the electrons of the heterocyclic ring. This interac-
tioncausesashorteningofC5 –NHbond(1.35–1.36 Å vs. 1.40 Å for
´
(0.327 vs. 0.349 a.u. and 1.363 vs. 1.351 Å for –NO2 and –NMe2,
respectively). The correlation of δ 17O values with the Hammett
parameters for oxadiazoles 5 is relatively poor (R2 ≈ 0.8), while
the general tendency is still seen. The weak correlation is a result of
small chemical shift range for this group of compounds. The errors
in estimation of the experimental values as well as the effects
of concentration, temperature and sample impurities significantly
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 648–654

17O NMR studies of substituted 1,3,4-oxadiazoles
Table 3. Statistical data for correlation analysis between the 17O NMR chemical shifts of the NO2 and OCH3 substituents oxygen atom and Hammett
constants for the compounds studied
Compounds
Parameter
ρ
sρ
i
si
n
r2
3a–3l and 2d
σp
1.44 0.16
σI: −0.56 0.05
σR: 1.62 0.23
1.47 0.14
55.84 0.07
56.00 0.16
13
13
0.88
0.89
σI and σR
4a–4k, 2m and 3l
σp
580.32 0.06
580.32 0.16
13
13
0.90
0.91
σI and σR
σI: 1.47 0.22
σR: 1.47 0.37
a Compounds with iodine and phenyl substituents were omitted.
influence the 17O chemical shifts, and the magnitudes of these
effects are similar to that of the Ar1 substituent, which worsens the
correlation coefficient. The presence of an NH group, an efficient
hydrogen bond donor and acceptor, makes the chemical shifts
of compounds 5 and 6 much more sensitive to environmental
effects. For the compounds with substituent varying in Ar2 group
(series 6), the correlation of chemical shifts with σ values is much
better (R2 > 0.95).
given for the equation: δexp 17O = ρδcalc 17O + intercept). Gen-
erally, the computed values are by about 50 ppm higher than
the measured but a global correlation, involving all experimen-
tal and calculated chemical shifts is excellent (R2 = 0.999). This
difference may be a result of the calculation procedure, which
does not take into account the solvation of the molecules and
the formation of the intramolecular hydrogen bonds. The sec-
ond effect could play a crucial role for the calculated shielding
of the water oxygen atom, the 17O NMR reference. Addition-
ally, the calculations were performed for frozen molecules at 0 K
and, in consequence, such effects as molecular dynamics and
molecules deformations were not included into the results ob-
tained. Although the relationships between the calculated and
experimental oxygen-17 chemical shifts are linear, the suscep-
tibility constants (ρ) are not equal to 1, which indicates that
the errors in δ 17O calculations depend on the electron-acceptor
character of the substituents. We have not found any simple
correlation between the calculated Mulliken or NBO charges on
oxygen atoms or on neighboring atoms with the experimental
values of chemical shifts. Such correlations between charges and
chemical shifts were observed only for rigid compounds.[20,21]
The molecules studied are able to rotate around single bonds as
well as can undergo inversion at NH nitrogen atoms, and these
processes preclude observation of a simple correlation between
charge and chemical shift. Good correlations (R2 > 0.9) were,
however, found for the calculated values of the CA –O bond length
and the experimental δ 17O NMR results (Table 2; correlation pa-
rameters given for the equation: δexp 17O = ρLC–O+ intercept).
Among the systems studied, only for 2-phenylamino-5-aryl-1,3,4-
oxadizoles (compounds of series 5) no correlation between the
calculated and experimental results or between the observed
chemical shifts and bond lengths was found. The origin of this
effect is unclear. Probably, in the calculations the interactions
of the lone pair on NH nitrogen atoms on the electron system
of oxadiazole ring are overestimated, and the role of the ex-
tended π-electron system including Ar1 ring and C N bonds is
minimized.
17O NMR chemical shifts of the oxygen atom of the NO2
and MeO substituents
The 17O NMR chemical shifts of both nitro and methoxy groups
bonded to aryl moiety undergo changes upon changing the
substituent in the second aryl group (compound groups 3 and
4). The ranges of these values are 2.5 and 2.6 ppm, respectively.
For both the series of compounds, the good correlation of these
values with the Hammett parameters was confirmed (Table 3).
Such significant and systematic, long-range effects indicate the
existenceofcoupled,extendedπ-electronsystems,includingboth
aryl moieties and C N bonds. It should be especially pointed out
that the effects observed on OMe and NO2 oxygen atoms are of the
same order of magnitude as those for oxadiazole ones, which are
located by six (or seven) bonds closer to the substituent changed.
This is in agreement with the earlier postulated explanation that
the heterocyclic oxygen atom lone pairs do not participate in the
resonance and electron delocalization, i.e. the 1,3,4-oxadiazole
system is low or either non-aromatic.
The long-range substituent effect on the δ 17O values is ob-
served for compounds for which no correlation of chemical shifts
of the intermediate carbon or nitrogen atoms with Hammett
parameters was detected.[7,8] For the Cipso –NO2(OMe) atom the
poor correlation (R2 0.75 and 0.81, respectively) of the chemical
shifts with Hammett parameters was assumed. Similar tendencies
were assumed for 1,3,4-oxadiazolines.[19] For these compounds as
well as for 1,3,4-oxadiazoles studied, no resonance formulas, i.e.
the coupled π-electron path allowing the transition of substituent
electronic effect, including all atoms showing the chemical
shift/Hammett constants correlation and omitting these ones,
which do not correlate, can be proposed.
Calculations performed with Polarizable Continuum Model
(PCM) give the worse agreement with experimental results than
these performed for molecules in vacuum. For compound of series
1 the PCM-calculated chemical shifts range is 320.7–331.8 ppm, if
PCM model was used for calculations of NMR parameters only, or
320.5–331.0 ppm if PCM approach was used also on the geometry
optimization stem (vs. experimental: 259.4–264.6 ppm; in gas-
phase calculations: 306.9–315.2 ppm). The correlation coefficient
obtained for equation δexp 17O = ρδcalc(PCM) 17O + intercept is
smaller for PCM calculations than for calculations in gas phase
(0.93 vs. 0.97).
17O NMR chemical shifts – theoretical calculations
The calculated chemical shifts and CA –O bond lengths were col-
lected in Table 1 (CA is an oxadiazole ring carbon atom connected
with the varying substituent in particular series). As follows, the
δ values differ significantly from the experimental ones, although
they correlate well with them (Table 2; correlation parameters
c
Magn. Reson. Chem. 2011, 49, 648–654
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

B. Gierczyk et al.
17ONMRchemicalshiftsofthe1,3,4-oxadiazoles – comparison
with the other heterocyclic compounds
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The observed chemical shifts of the oxadiazole ring are similar
to those found for furans[22] (240.0 ppm for furan, 255.5 ppm for
2,5-dimethylfuran) and oxazoles[23] (247 ppm for 2,5-diphenyl-1,
3-oxazole). These compounds are usually recognized as aromatic,
but the recent studies indicate that their aromaticity is rather
low.[12–14] The 17O NMR 1,3,4-oxadiazole signals occur in the same
region as oxygen of non-aromatic lactone, 5-methylfuran-2(3H)-
one (239 ppm).[16] The oxygen-17 signals of aromatic pyrylium
salts are distinctly deshielded (270–300 ppm).[16]
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M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajama,
Y. Honda, O. Kiato, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchin,
J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Startmann,
O.Yazyev,A. J.Austin,R.Cammi,C.Pomelli,J. W.Octerski,P. Y.Ayala,
K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenbeg, V. G.
Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farks, D. K.
Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz,
Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov,
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Conclusions
The 17O NMR chemical shifts of 72 mono- and disubstituted
oxadiazoles were determined and correlated with Hammett
coefficients, calculated chemical shifts and bond lengths. The
influence of structural parameters on the observed effects was
discussed. The presence of long-range substituent effects on 17O
chemical shifts as well as an unusual transfer of the electronic
effects via sp3 nitrogen atom was observed. The low or either
non-aromatic character of oxadiazole ring was confirmed.
[13] S. I. Kotelevskii, O. V. Prezhdo, Tetrahedron 2001, 57, 5715.
[14] T. M. Krygowski, M. Cyran´ski, Tetrahedron 1996, 52, 10255.
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Acknowledgements
Calculations were performed in Poznan Supercomputing –
Network Centre.
[17] P. Balakrishnan, A. L. Baumstark, B. W. Boykin, Tetrahedron Lett.
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Magn. Reson. Chem. 2011, 49, 648–654