Oximes in the Isoxazolone, Pyrazolone, and 1,2,3-Triazolone Series: Experimental and Computational Investigation of Energies and Structures of E/Z Isomers of α-Oxo-Oximes in the Gas Phase and in Solution

Article abstract of DOI:10.1071/CH15095

The structures of a series of heterocyclic α-oxo-oximes, viz. 4-oximinoisoxazolone-5(4H)-ones 1 and 2,4-oximino-5(4H)-pyrazolones 3-5, and 4-oximino-1-phenyl-1,2,3-triazol-5(4H)-one 6, were investigated experimentally and computationally. Whereas the intr

Full text of DOI:10.1071/CH15095

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2015, 68, 1329–1335
Full Paper
http://dx.doi.org/10.1071/CH15095
Oximes in the Isoxazolone, Pyrazolone, and
1,2,3-Triazolone Series: Experimental and Computational
Investigation of Energies and Structures of E/Z Isomers
of a-Oxo-Oximes in the Gas Phase and in Solution
A D
,
B
B C D
, ,
Rainer Koch,
Hans-Joachim Wollweber, and Curt Wentrup
A
Institut fur Chemie and Center of Interface Science, Carl von Ossietzky Universitat
¨
¨
Oldenburg, PO Box 2503, 26111 Oldenburg, Germany.
B
Fachbereich Chemie der Philipps-Universitat Marburg, 35037 Marburg, Germany.
¨
C
School of Chemistry and Molecular Biosciences, The University of Queensland,
Brisbane, Qld 4072, Australia.
D
Corresponding authors. Email: rainer.koch@uni-oldenburg.de; wentrup@uq.edu.au
The structures of a series of heterocyclic a-oxo-oximes, viz. 4-oximinoisoxazolone-5(4H)-ones 1 and 2,4-oximino-5(4H)-
pyrazolones 3–5, and 4-oximino-1-phenyl-1,2,3-triazol-5(4H)-one 6, were investigated experimentally and computation-
ally. Whereas the intramolecularly H-bonded ZZ isomers of these oximes are usually the most stable in the gas phase, this
preference is overcome by intermolecular H-bonding to a solvent or another molecule. For 1,3-dimethyl-4-oximino-
5(4H)-pyrazolone 3b a turnaround is seen when going from the solid (predominantly Z isomer) to DMSO solution
(predominantly E isomer), which can be ascribed to an intermolecular H-bond between the oxime OH function and a
DMSO molecule. Such isomerization is not seen in CDCl3, where intermolecular H-bonding is unimportant. The Z/E-
isomerization in DMSO solution is accelerated by photolysis. Calculations of the energies of different conformers, and
of 13C NMR data at the GIAO-vb97xD/6-31G(d)//M06-2X/6-311þþG(d,p) level permit a clear-cut correlation of
conformer structures with observed 13C NMR spectra.
Manuscript received: 26 February 2015.
Manuscript accepted: 2 April 2015.
Published online: 29 April 2015.
Introduction
structures ZZ, ZE, EE, and EZ shown for a-oximinoketones
(monoximes of a-diketones) in Chart 1. It can be important to
distinguish these because, as discussed in this paper, the ZZ
isomer can form intramolecular H-bonds to the C¼O groups, but
the other three can form intermolecular H-bonds, which may be
more important and thus influence the relative energies and
spectroscopic properties.
While the absolute structure of a crystalline oxime may be
determined by X-ray crystallography, this does not necessarily
reveal anything about the structure in solution, because some
oximes have the tendency to crystallize in a form not expected
from thermodynamic considerations. This can be ascribed to
crystal lattice forces overcoming the usually small E/Z energy
difference. Thus, acetaldoxime crystallizes as the Z isomer at
08C,[2] but this material equilibrates in solution to give an E/Z
ratio of ,40 : 60, corresponding to a free energy difference of
0.27 kcal molꢀ1 in favour of Z at 408C.[3]
Although the structures and properties of oximes have been
investigated for over 130 years,[1] there are still important
questions, such as which isomer, E or Z, is the most stable, and
how do we determine this from spectroscopic data? E/Z
isomerization in aldoximes was formerly called syn/anti
isomerization, which was defined with respect to the orientation
of the imine CH (or the smallest group in ketoximes); thus, in
many cases E corresponds to syn (Chart 1).
Four structures are required in order to specify the orientation
of the hydrogen atom in the N–OH function, for example the
OH
N
H
R
H
R
N
OH
E (syn)
Z (anti)
Reva and co-workers were able to vaporize the Z isomer from
the crystalline acetaldoxime, isolate it in an Ar matrix, and
obtain the IR spectrum. If the sample was first melted, Z/E
equilibration occurred, and the resulting Z/E mixture was
observed in the IR spectrum. When a liquid sample was frozen,
the vapour over this solid was enriched in the E isomer.[4]
Phenylacetaldoxime also crystallizes as the Z isomer, which
is therefore obtained initially on dissolution of the solid, but this
H
O
H
O
H
N
N
O
N
N
O
H
Y
Y
Y
Y
O
O
O
O
X
X
X
X
ZZ
ZE
EE
EZ
Chart 1. Oxime structure notations.
Journal compilation Ó CSIRO 2015
www.publish.csiro.au/journals/ajc

1330
R. Koch, H.-J. Wollweber, and C. Wentrup
solution changes to predominately the thermodynamically pre-
ferred E isomer in the course of two days in benzene solution at
room temperature, giving an E/Z ratio of 54 : 46, corresponding
to a free energy difference of 0.1 kcal molꢀ1 in favour of E.[3]
Calculated barriers for pure, intramolecular E/Z isomeriza-
tion in oximes in the gas phase are substantial, of the order of
55–60 kcal molꢀ1, and they take place by nitrogen inversion,[5]
but in the liquid state and in solution they are highly dependent
on solvent polarity, acids and bases, and association.[4,6–8]
Therefore, dramatically lower apparent activation barriers
may be observed in solution. This makes it even more difficult
to determine the preferred structures in solution. In the 1H NMR
spectrum of acetaldoxime, CH3C(H)¼N–OH, the quartet due to
the methine proton of the E isomer resonates at higher field than
that of the Z form in the neat liquid or in benzene solution,[3]
but the opposite is observed in D2O solution.[7] The enthalpy
of activation for E/Z interconversion was determined as
13 kcal molꢀ1 in D2O and about 16 kcal molꢀ1 in CCl4.[7] The
energy difference between the Z and E isomers was determined
to be less than 1 kcal molꢀ1 (E/Z ¼ 0.5–0.8 for various solvents,
concentrations, and temperatures) and the preponderance of the
Z isomer was ascribed not to its lower intrinsic energy but to
preferential self-association of this isomer by intermolecular
H-bonding. The lowest and highest E/Z ratios (0.5 and 0.8) were
found in heptane and water, respectively. In the former, self-
association is the most important; in the latter, intermolecular
H-bonding with the solvent becomes important.[8]
and 1,2,3-triazol-5(4H)-ones[17] as well as the iminoxyl radicals
generated by oxidation (Eqn 1) caused us to examine the nature
of this type of oximes more closely. The results are reported
herein.
OH
N
O
N
ꢂ
ꢀ
FVT
ox
Y
Y
H
C
N
O
N
N
ꢀXCO
ꢀNY
O
O
X
X
ð1Þ
a: X ꢁ O, Y ꢁ CCH3
b: X ꢁ NPh, Y ꢁ N
Results and Discussion
The oximes examined here are shown in Chart 2. The compounds
were examined by 1H and 13C NMR spectroscopy. In addition,
their geometries were optimized at the M06-2X/6-311þþG(d,p)
level of theory both in the gas phase and in a simulated DMSO
solvent field; the respective relative energies are given in Table 1.
HO
N
N
OH
H3C
H3C
N
N
O
O
O
O
1Z
1E
In the 13C NMR spectra, a Z-methyl group in acetone oxime,
(CH3)2C¼N–OH, resonates at higher field (6.5 ppm higher than
the E-methyl), and this was ascribed to a screening effect of the
Z-OH group.[9] In the acetophenone oxime, Ph(CH3)C¼N–OH,
the E(syn)-CH3 group appears at a 9 ppm higher field than the
Z(anti)-CH3 in CDCl3 solution.[10] The imine carbon of the
E isomer appears at lower field than that of the Z isomer. In
isatin-3-oximes (isatoximes) and isatoxime ethers, the E-imine
carbon again resonates at the lower field (147 versus 145 ppm),
and the carbonyl group (C2) in the E isomer also appears at
lower field (163 versus 157 ppm).[11] These oxime derivatives
are reasonably stable configurationally, so that X-ray crystal
structures can be used to aid the analysis of solution NMR data.
In the case of 1,2-naphthoquinone 2-oxime, Z/E isomerization
barriers of 49–52 kcal molꢀ1 (in the gas phase) were calculated
at B3LYP and MP2 computational levels, and the lower-field
C¼O and C¼N signals in the 13C NMR spectrum (181 and
147 ppm, respectively) were assigned to the EE isomer based on
calculations.[12] In a similar study, Ivanova et al. also concluded
that the EE form was the major constituent, with a minor amount
of the ZZ isomer postulated.[13] Here, the 13C¼O signal was
shifted upfield by 1.3 ppm in the ZZ isomer. Both studies[12,13]
emphasized the importance of inclusion of solvent effects
(polarizable continuum model (PCM)) or the explicit inclusion
of a DMSO molecule in the calculations in order to obtain
correct relative energies in solution. In the cases of phenalene-
1,2,3-trione 2-oxime and indane-1,2,3-trione 2-oxime, the lower
field CO resonances were assigned to the ZZ structures for no
obvious reason and probably erroneously; here, the two isomers
equilibrated at 360 K in DMSO solution.[14] These examples
demonstrate the need for great care in deducing structures of
oximes from NMR spectra and in deciding on preferred isomer
structures based on energy calculations.
HO
N
N
OH
N
N
O
O
O
O
2Z
2E
HO
N
NOH
O
N
OH
H3C
H3C
H3C
N
N
N
O
O
N
N
N
R
R
R
3aZ
3bZ
3cZ
3aE
3bE
3cE
3a R ꢁ H
3b R ꢁ CH3
3c R ꢁ Ph
HO
N
Ph
N
NOH
OH
Ph
Ph
N
N
N
O
O
O
N
R
N
N
R
R
4a R ꢁ H
4b R ꢁ CH3
4aZ
4bZ
4aE
4bE
N
OH
O
N
O
Ph
N
Ph
5
HO
N
NOH
N
OH
N
N
N
N
N
N
N
O
O
N
O
N
Ph
Ph
Ph
6
6ZC
6EC
Our interest in the chemistry of isoxazolones and related
heterocycles,[15] in particular the very practical synthesis
of fulminic acid, HCNO, by flash vacuum thermolysis of
4-oximino derivatives of isoxazol-5(4H)-ones,[16] pyrazolones
Chart 2. Oximes investigated in this paper. For compound 6 the same Z/E
convention as for 1–5 is applied; this is indicated by the symbols ZC and EC,
indicating that the stereochemistry is defined with respect to the C¼O group.

Oxime E/Z Isomers
1331
NMR spectroscopic data were calculated at the GIAO-PCM-
vb97xD/6-31G(d)//PCM-M06-2X/6-311þþG(d,p) level, which
has proved its reliability in an extensive test of methods for
the NMR calculation of heterocycles.[18] Calculations at the
B3LYP/6-31G(d) level were also performed for several of the
compounds in the present study, but these did not yield any
further insight and are therefore not included in this paper.
The influence of simulated DMSO and CDCl3 solvation on the
energies and NMR chemical shifts was investigated using the
PCM model. The data are presented in Table 2.
Table 1. Relative energies (kcal mol21) of gas phase and solvated
isomers of compounds investigated herein (M06-2X/6-31111G(d,p))
In the case of 3-methyl-4-oximinoisoxazolone 1 both the Z
and the E form of the oxime are observable by 13C NMR
spectroscopy, and the E isomer dominates. The structural
assignments were made on the basis that the CH3 group of the
Z isomer appears at the higher field in both the 1H NMR
spectrum (2.2 ppm) and the 13C NMR (10.7 ppm). C¼O func-
tions in Z-oxime isomers are expected to be shifted significantly
upfield; for 1Z to 159 ppm compared with 165 ppm for 1E. The
upfield shifts of the Z-C¼O groups in isatin-3-oxime deriva-
tives, where secure X-ray structures are available,[11] are impor-
tant points of reference.
The initial E/Z ratio for 1 measured shortly after dissolution
in DMSO-d6 was 94 : 6. After 48 h the E/Z ratio had fallen to
80 : 20. Therefore, it can be concluded that the solid oxime exists
largely in the E form, but equilibration of the two isomers occurs
in solution at room temperature. The changing E/Z ratio allows a
straightforward correlation of 1H and 13C NMR spectra.
Phenomenologically the upfield shift of the Z-C¼O group
can be rationalized by noting that intramolecular (chelating)
Compound
Gas phase
DMSO
ZE EE
ZZ ZE
EE
EZ
ZZ
EZ
1
0
0
0
0
0
1.5
3.4
1.9
3.2
3.6
0.9
0.0
3.2
2.5
2.9
9.6
8.7
0
0
ꢀ1.3 ꢀ1.7 4.9
1.6 ꢀ1.9 4.8
ꢀ1.2 ꢀ0.2 4.5
Isatin-3-oxime 7
2a
8.0
0
3a
10.4
10.7
0
0.6
0.9
1.7
0.7
0.6
1.3
–
0.0 5.9
0.3 6.2
1.1 7.7
0.1 8.2
1.4 5.6
1.2 5.2
3b
3b (CDCl3)A
0
0
3c
4a
4b
5
0
0
3.5
3.8
4.2
–
2.8
4.9
15.0
9.2
9.0
–
0
0
0
4.7
0
Z 0
0
E 2.3
1.1
Z 0
0
E 0.1
–
6B
1.5
1.6
ꢀ0.7 ꢀ1.7 0.2
AEnergies for CDCl3 instead of DMSO solution.
BFor compound 6 the same Z/E convention as for 1–5 is applied, i.e. the
stereochemistry is defined with respect to the C¼O group (see caption for
Chart 2).
Table 2. Experimental and computed 13C NMR chemical shifts (in ppm, relative to TMS, for DMSO-d6 solutions)
Compound
Experimental dataA
Computed data
1ZZ
1ZE
1EE
1EZ
12.8, 137.7, 155.7 (CO), 158.2 (C(N)–Me)
13.3, 136.4, 150.0 (CO), 157.9 (C(N)–Me)
17.2, 136.1, 151.1 (C(N)–Me), 159.0 (CO)
15.0, 135.2, 147.7 (C(N)–Me), 158.3 (CO)
10.7, 139.6, 156.6, 159.8
15.0, 139.0, 153.6, 165.0
1ZEꢁDMSOB
1EEꢁDMSOB
13.4, 134.2, 150.8, 158.4
17.3, 133.9, 150.8, 160.9
1EEꢁDMSOUHC
16.6, 131.7, 153.2, 174.2
7ZZ
7ZE
7EE
7EZ
26.5, 5 Carom, 139.8, 141.0, 156.3
26.6, 5 Carom, 140.4, 140.8, 151.1
26.9, 5 Carom, 141.6, 142.3, 157.8
27.9, 5 Carom, 141.0, 142.0, 157.2
25.6, 5 Carom, 142.7, 143.2, 163.9
4 Carom, 139.3, 155.5, 158.4
2ZZ
2ZE
2EE
2EZ
6 Carom, 136.8, 156.1, 157.4
6 Carom, 135.4, 150.2, 157.3
6 Carom, 133.6, 153.2, 158.9
6 Carom, 133.9, 150.9, 158.3
3bZZ
3bZE
3bEE
3bEZ
12.1, 30.4, 143.8, 146.0, 152.3
16.0, 30.8, 139.5, 143.6, 160.4
14.2, 33.5, 142.9, 144.6, 152.2
14.6, 33.9, 141.6, 143.1, 147.4
19.1, 34.0, 136.3, 141.5, 155.7
16.9, 34.1, 132.2, 140.5, 155.3
5Z
5E
6 Carom, 141.5, 152.0, 158.4
12 Carom, 136.2, 150.1, 151.8
12 Carom, 134.8, 146.0, 151.9
6ZZD
6ZE
6EE
6EZ
5 Carom, 132.2, 150.4 (CO), 151.1 (CN)
5 Carom, 133.0, 145.7 (CO), 149.0 (CN)
5 Carom, 130.6, 143.3 (CN), 154.2 (CO)
5 Carom, 130.2, 146.5 (CN), 153.2 (CO)
3 Carom, 136.3 (C1-aryl), 145.8 (CN), 160.3 (C¼O)
AAssignment of experimental data to an isomer is based on the calculated relative energies.
BA DMSO molecule is coordinated to the oxime OH-group (see text).
C
˚
A proton has been placed at a fixed distance of 1.45 A from the C¼O group oxygen (see text).
DFor the stereochemical notation for compound 6 see caption for Chart 2.

1332
R. Koch, H.-J. Wollweber, and C. Wentrup
H-bonding in b-dicarbonyl compounds also leads to an upfield
shift of the H-bonded carbonyl carbon atom.[19] However,
following the work of Caldeira and Gil,[8] the effect may be
due to self-association and/or H-bonding with the solvent rather
than intramolecular H-bonding. Therefore, experimentally we
can only determine whether the compounds are E or Z; calcula-
tions are required to determine the relative importance of ZZ,
ZE, EE, and EZ isomers.
isoxazolone 1. In the case of 1,3-dimethyl-4-oximinopyrazolone
3b the E/Z ratio is dependent on the solvent used for crystalliza-
tion as well as the solvent used for the NMR measurement. The
E/Z ratio changes from an initial excess of the Z isomer to an
excess of the E isomer in the course of 5 days in DMSO-d6
solution at room temperature – but it stays largely unchanged
in CDCl3. We ascribe this phenomenon to intermolecular
H-bonding to DMSO, favouring the E isomer. Moreover,
UV-irradiation of a DMSO-d6 solution of 3b for 2 h using a
75 W low-pressure Hg lamp causes a change of the E/Z ratio
from 18 : 82 to 60 : 40, and it then stays at this value for at least
48 h in the dark at room temperature. Similar irradiation of a
CDCl3 solution had no such effect. Presumably, population of
the excited state of the oxime facilitates isomerization from Z to
E in DMSO solution, but any such isomerization would be
thermally reversed in CDCl3 solution, where the Z isomer is
the most stable.[21] Our calculations predict the ZZ form to be
preferred by about 3 kcal molꢀ1 in the gas phase. In a simulated
chloroform environment, it remains the most stable isomer by
1.1–1.7 kcal molꢀ1, in agreement with the unchanged E/Z ratio
in CDCl3. Inclusion of DMSO solvation in the calculations leads
to nearly equally stable EE and ZZ isomers of 3b, in line with the
observed ratio. Thus, this is another example of an oxime that
crystallizes in the intramolecularly H-bonded ZZ form but
changes (in part) to the solvent-stabilized EE form in DMSO
solution (Scheme 1).
For calculations of the gas-phase structures, the ZZ isomer
with an intramolecular H-bond between the OH and C¼O group
is always the lowest energy. In all cases, solvation increases the
relative energy of the ZZ conformer by 2–3 kcal molꢀ1, as the
intramolecular H-bonds become less important. For 1, M06-2X
predicts EE to be the most stable, followed by ZE lying
0.4–0.5 kcal molꢀ1 higher, in both CDCl3 and DMSO, in excel-
lent agreement with the experimental data. Explicit solvation
with an additional DMSO molecule coordinating at the OH
moiety also favours the EE form, and its preference over 1ZZ
remains unchanged (see Table S1, Supplementary Material).
It is striking that none of the computational approaches gave
a value close to the experimental value of 165 ppm for the
carbonyl carbon in 1EE. The deviations are 5–10 ppm, resulting
in too small chemical shifts. Similar trends are observed for most
of the other investigated compounds. However, when a proton is
placed near the carbonyl oxygen atom at a typical H-bond
distance (OꢁꢁꢁH ¼ 1.45 A), simulating H-bond donation from
another oxime molecule, the C¼O carbon shifts to lower field at
,174 ppm (see Table 2). This indicates the importance of
intermolecular H-bonds in 1EE due to either self-association
or solvation (although explicit DMSO solvation does not lead to
significant changes in the 13C chemical shifts). In general, the
calculated spectra for 1EE and 1ZE agree quite well with the
experimental data.
For the reference compound isatin-3-oxime 7 (Chart 3) the
relative energy calculated for the EE isomer (in DMSO) is the
lowest, and the simulated NMR data agree well with this
finding.[20]
It is observed that the C¼O signal in the ZE isomer is shifted
upfield by about 5 ppm compared with all other conformers,
regardless of the computational method and the investigated
molecule. This is probably due to a shielding effect of the
neighbouring HO lone pair, which is closest to the C¼O group
in this isomer.
In 3-phenyl-4-oximinoisoxazolone 2, steric hindrance has
the result that only the Z isomer was detected by 13C NMR
spectroscopy as judged by the upfield chemical shift of the C¼O
group (158 ppm). This is in agreement with the calculations,
which predict the ZE isomer to have the lowest energy in DMSO
(ZZ is most stable in the gas phase). There is also good
agreement between the measured and the simulated NMR data
(both for DMSO solution).
Compound 3c was similar to 3a and 1, affording an E/Z ratio
of ,75 : 25 immediately upon dissolution in DMSO, but this
changed to ,30 : 70 in 7 days at room temperature. The EE and
the ZZ forms are predicted to have similar stabilities.
In the oximopyrazolones 4, the Z forms remain more stable
even in solution, according to the calculations. As in the case of
2, steric hindrance by the phenyl group disfavours E isomers.
The large chemical shifts of the OH peaks in the experimental 1H
NMR spectra point to the presence of the most stable ZZ form
(see the Supplementary Material for details of 1H NMR calcula-
tions). 1,2-Diphenyl-4-oximinopyrazolidin-3,5-dione 5 exists
only in one E or Z conformation due to its symmetry (ZZ ¼ EZ
and EE ¼ ZE). The calculations predict both forms to be equally
stable in DMSO; the simulated NMR data fit the Z form better.
In the case of the oximinotriazole 6 the calculations predict
the lowest energy for the ZZ form in the gas phase (for
compound 6 we have applied the same Z/E convention as for
1–5; see caption for Chart 2). This ordering is – again – reversed
in DMSO solution. In agreement with this, the computed NMR
data clearly indicate that the EE conformer is the observed form
in DMSO-d6.
Conclusion
The preferred configurations of a-oxo-oximes can be under-
stood on the basis of steric hindrance (at C3, disfavouring E
isomers), lone-pair repulsion between C¼O and OH groups
Both E and Z isomers of the 3-methyl-4-oximinopyrazolones
3 are observable by NMR spectroscopy. In the case of 3a the
E isomer dominates, analogously with the situation for the
H
O
HO
N
N
N
H3C
H3C
O
H
DMSO
CDCI3
N
N
O
O
N
N
O
N
CH3
CH3
3bEE
CH3
3bZZ
Chart 3. Isatin-3-oxime 7.
Scheme 1. Solvent-dependent interchange of 3bZZ and 3bEE isomers.

Oxime E/Z Isomers
1333
(disfavouring ZE isomers), and, most importantly, intra-
molecular H-bonding (favouring ZZ isomers) and intermole-
cular H-bonding (favouring EE isomers). Thus, for example,
3-methyl-4-oximinoisoxazolone 1 exists predominantly in the
EE configuration, but the larger phenyl group causes oxime 2 to
exist almost exclusively in the ZE configuration. The dimethyl-
oximinopyrazolone 3b crystallizes to give a preponderance of
the intramolecularly H-bonded ZZ isomer, which is therefore
observed as the major isomer by NMR spectroscopy in either
CDCl3 or DMSO-d6 solution immediately upon dissolution, but
it changes to an excess of the EE isomer in the course of 5 days in
DMSO solution. This process is accelerated by photolysis in
DMSO, but not in CDCl3 solution and is ascribed to inter-
molecular H-bonding of the EE isomer with DMSO molecules.
CDCl3: E/Z ¼ 12/88. Compound 3b recrystallized from H2O,
measured immediately after dissolution, in DMSO-d6: E/Z ¼
31 : 69; in CDCl3: E/Z ¼ 18/82; after 5 d at room temperature: in
DMSO-d6: E/Z ¼ 64 : 36; in CDCl3: E/Z ¼ 23/77. dC (DMSO-
d6) Z-isomer: 12.1, 30.4, 143.8, 146.0, 152.3; E-isomer: 16.0,
30.8, 139.5, 143.6, 160.4.
3-Methyl-4-oximino-1-phenylpyrazol-5(4H)-one 3c was pre-
pared according to Knorr[25] from 3-methyl-1-phenylyrazol-
5(4H)-one (5.30 g; 0.031 mol) and sodium nitrite and obtained
as a yellow solid (5.23 g; 83%), mp 153–1578C from acetic acid
(lit.[25] 1578C). lmax (KBr)/cmꢀ1 3260s (broad), 1695 s, 1615m,
1585m, 1495m, 1420m, 1360 m, 1305m, 1030s, 995 m, 990 m,
750 m. dH (CDCl3) E-isomer (major): 2.60 (s, 3H), 7.4–8.3 (m,
5H); Z-isomer (minor): 2.42 (s 3H), 7.4-8.3 (m, 5H); E/Z ratio
measured immediately after dissolution: 75: 25, and similar in
DMSO-d6. dC (DMSO-d6) 12.4, 151.4 (Z); 17.3, 159.4 (E);
E and Z isomers 118.1, 125.0, 128.9, 137.7, 141.9, 144.0, 148.0.
4-Oximino-3-phenylpyrazol-5(4H)-one 4a was prepared
according to Ponzio and Ruggeri[26] and obtained as a yellow-
orange solid, mp 177–1828C (with mild decomposition) (lit.[26]
1808C); lmax (KBr)/cmꢀ1 3500m (broad), 3230s (broad),
2960m (broad), 2900m (broad), 1695s, 1650s, 1600m,
1455m, 1035 s, 915 s, 755 s, 740 s, 655 m. dH (DMSO-d6) (only
one isomer present): 7.46 (m, 3H), 7.94 (m, 2H), 11.90 (br s).
1-Methyl-4-oximino-3-phenylpyrazol-5(4H)-one 4b was
prepared according to Michaelis[27] and obtained as a yellow-
orange solid, mp 157–1648C (subl. .758C) (lit.[27] 1628C), lmax
(KBr)/cmꢀ1 3120 s (broad), 2970 s (broad), 2820 s (broad),
1660 s, 1600 m, 1455 s, 1395 m, 1030 s, 965 m, 890 s, 740 s,
680 m, 660 m, 640 m. dH (DMSO-d6) (only one isomer present):
3.34 (s, 3H), 7.46 (m, 3H), 7.92 (m, 2H), 14.60 (br s).
Experimental
Note: as described in the text, NMR spectroscopy can only
determine the presence of Z or E isomers, and their ratio. The
NMR calculations are required in order to assign spectra to ZZ,
ZE, EE, and EZ structures. The results of such analyses are
presented in Table 2.
3-Methyl-4-oximinoisoxazol-5(4H)-one 1 was prepared in
84 % yield according to the literature method[22] and obtained
as a white solid, mp 139–1418C (lit.[22] 141–1428C). dH (DMSO-
d6) E-isomer (major): 2.38 (s, 3H); Z-isomer (minor): 2.20 (s,
3H); both isomers: 10.4 (br s, 1H); E/Z ratio 30 min after
dissolution: 94 : 6. E/Z ratio 48 h after dissolution: 80 : 20. dC
(DMSO-d6) E-isomer (major): 15.0, 139.0, 153.6, 165.0;
Z-isomer (minor): 10.7, 139.6, 156.6, 159.8. lmax (KBr)/cmꢀ1
3540–2400 (broad; maximum at 3220), 1755 vs, 1430 s, 1210 s,
1080 s, 1035 s, 855 s. m/z 128 (Mþ, 5 %), 100 (3), 70 (8), 67 (4),
44 (99), 43 (75), 41 (100), 40 (55).
3-Phenyl-4-oximinoisoxazol-5(4H)-one 2 was prepared in
75 % yield according to the literature method[23] and obtained
as yellow crystals, mp 1438C (lit.[23] 1438C). dH (DMSO-d6)
7.4–7.7 (m, 5H), 9.8 (br s, 1H). dC (DMSO-d6) (Z-isomer) 125.4,
127.0, 127.8, 131.7, 139.3, 155.5, 158.4. lmax (KBr)/cmꢀ1
3200–2800 (broad; maxima at 3120 and 2830), 1785 vs,
1460 s, 1380 m, 1165 m, 1045 vs, 950 m, 880 s, 755 m, 735 m,
680 m, 660 m. m/z 190 (Mþ, 3 %), 103 (100), 77 (14), 76 (33),
51 (10), 50 (14), 45 (32), 44 (18). Anal. Calc. for C9H6N2O2:
C 256.85, H 3.18, N 14.73. Found: C 57.10, H 3.54, N 14.75.[21]
3-Methyl-4-oximinopyrazol-5(4H)-one 3a was prepared in
84 % yield by the literature method;[24] mp 234–2358C (lit.[24]
2308C). dH (DMSO-d6) Z-isomer: 2.06 (s, 3H), 11.34 (br s, 1H);
E-isomer: 2.24 (s, 3H), 11.39 (br s, 1H); E/Z ratio immediately
after dissolution: 70 : 30. lmax (KBr)/cmꢀ1 3500–2800 (broad),
1695 s, 1610 s, 1275 s, 1045 s, 1020 s, 970 s, 730 s.
1,3-Dimethyl-4-oximinopyrazol-5(4H)-one 3b was prepared
from 1,3-dimethylpyrazol-5(4H)-one (4.5 g; 0.08 mol) and
NaNO2 by the method of Knorr[25] and obtained as a yellow
solid (8.58 g; 76 %), recrystallized from either CCl4 or H2O, mp
144–1458C; lmax (KBr)/cmꢀ1 3160 s (broad), 3000 s (broad),
2860 s (broad), 1675 s, 1615 m, 1455 m, 1030 s, 770 m. dH
(DMSO-d6) E-isomer (minor): 2.26 (s, 3H), 3.21 (s 3H);
Z-isomer (major): 2.08 (s 3H), 3.19 (s, 3H); both isomers: 15.3
(br s). dH (CDCl3) E-isomer (minor): 2.40 (s, 3H), 2.37 (s, 3H);
Z-isomer (major): 2.26 (s 3H), 3.39 (s, 3H); both isomers: 15.5
(br s). The E/Z ratio is dependent on the solvent used for
crystallization as well as the solvent used for NMR measure-
ment. Compound 3b recrystallized from CCl4, measured
immediately after dissolution, in DMSO-d6: E/Z ¼ 18 : 82; in
1,2-Diphenyl-4-oximinopyrazolidin-3,5-dione 5 was prepared
asdescribedbyTsumaki[28] andobtainedasayellow-orangesolid
containing crystal water, mp 96–998C. The monohydrate melts at
1038C.[29] The red, anhydrous compound melts at 163–1648C.[27]
l
max (KBr)/cmꢀ1 3420m (broad), 2830 m (broad), 1755s, 1720
vs, 1500s, 1310s, 1050s, 770 m, 750 m. dC (DMSO-d6) 123.4,
123.7, 125.9, 128.7, 135.3, 137.1, 141.5, 152.0, 158.4. For other
spectroscopic properties, see Mondelli.[30]
4-Oximino-1-phenyl-1,2,3-triazol-5(4H)-one 6[31] is light-
sensitive and should be shielded from light during preparation
and storage. It was prepared by nitrosation of 1-phenyl-5-oxo-
1,2,3-triazole-4-carboxylate (0.02 mol) with NaNO2 in alkaline
solution. As described by Dimroth and Taub,[31] the initially
formed red-blue dissolved product (probably the isomeric
diazo-nitrosoacetanilide) precipitates on acidification as the
oxime 6 in the form of a yellow powder (4 g; 97 %) with mp
130–1908C, whereby decomposition occurs at 190–2108C with
a colour change from yellow over green to brown. The IR
spectrum (KBr) of the yellow solid (oxime form) shows broad
absorptions with maxima at 3460 and 2640 cmꢀ1 and a strong
C¼O band at 1720 cmꢀ1. The compound is soluble in CHCl3
and diphenyl ether without change. It is sparingly soluble in
acetone and ethanol with complete transformation into the blue-
green 4-nitroso-1,2,3-triazol-5-one isomer. The IR spectrum of
the blue-green solid from acetone shows only a weak, broad
absorption at 3320 cmꢀ1 (NH) and a strong absorption at
1655 cmꢀ1. The blue-green compound was not obtained in a
pure state, and it decomposes above 408C. The yellow solid
dissolves in DMSO with intense green colour, presumably as a
mixture of the yellow oxime and the blue nitroso compound, but
the dissolved material decomposes at room temperature in the
course of a few hours with a colour change to yellow-orange.

1334
R. Koch, H.-J. Wollweber, and C. Wentrup
Yellow (oximino-triazolone), red (diazo-nitrosoacetanilide),
and green (nitroso-triazolone) salts, and yellow (oxime) and
red (diazo) acyl derivatives of 6 have also been described.[32]
dH (DMSO-d6) of compound 6 7.21–7.60 (m, 3H), 7.78–7.89
(m, 2H). dC (DMSO-d6) of compound 6 119.5 (CH), 126.3 (CH),
129.2 (CH), 136.3 (C1-aryl), 145.8 (CN), 160.3 (C¼O).
(b) NMR: W. Holzer, Z. Gyorgydeak, J. Heterocycl. Chem. 1996, 33,
675. doi:10.1002/JHET.5570330326
(c) X-ray (EE structure): Y. Miao, X. Zhang, C. Liu, J. You, Acta
Crystallogr. Sect. E: Struct. Rep. Online 2011, 67, o1291. doi:10.1107/
S1600536811015418
[12] A. Krzan, J. Mavri, Chem. Phys. 2002, 277, 71. doi:10.1016/S0301-
0104(02)00282-3
[13] G. Ivanova, V. Enchev, Chem. Phys. 2001, 264, 235. doi:10.1016/
S0301-0104(01)00245-2
Computational Methods
[14] V. Enchev, G. Ivanova, A. Ugrinov, G. D. Neykov, S. Minchev,
N. Stoyanov, J. Mol. Struct. 1998, 440, 227. doi:10.1016/S0022-2860
(97)00268-8
[15] (a) G. I. Yranzo, J. Elguero, R. Flammang, C. Wentrup, Eur. J. Org.
Chem. 2001, 2209. doi:10.1002/1099-0690(200106)2001:12,2209::
AID-EJOC2209.3.0.CO;2-X
(b) H. S. Rzepa, C. Wentrup, J. Org. Chem. 2013, 78, 7565.
doi:10.1021/JO401146K
[16] (a) C. Wentrup, B. Gerecht, H. Briehl, Angew. Chem. Int. Ed. Engl.
1979, 18, 467. doi:10.1002/ANIE.197904671
Calculations were performed with the program package Gauss-
ian 09.[33] Structures were optimized using the global hybrid
functional M06-2X[34] with the 6-311þþG(d,p)[35] basis set. In
additional optimizations, solvent effects were included via the
PCM[36] with a dielectric constant of 46.826 (DMSO) and 4.7113
(chloroform). Chemical shifts based on the PCM(DMSO)
geometries were computed by using the gauge invariant atomic
orbital method[37–39] (GIAO) and the dispersion corrected
v-B97xD functional[40] with the 6-31G(d) basis set.[41–43] Again,
a simulated DMSO solvent field was applied. The PCM calcu-
lations were performed with the default settings for the respective
solvent (see Supplementary Material for details).
(b) B. Winnewisser, P. Jensen, J. Mol. Spectrosc. 1983, 101, 408.
doi:10.1016/0022-2852(83)90145-5
(c) T. Pasinszki, N. Kishimoto, K. Ohno, J. Phys. Chem. A 1999, 103,
6746. doi:10.1021/JP991394N
(d) G. Schulze, O. Koja, B. P. Winnewisser, M. Winnewisser, J. Mol.
Struct. 2000, 517–518, 307. doi:10.1016/S0022-2860(99)00260-4
(e) W. Feng, J. F. Herschberger, J. Phys. Chem. A 2012, 116, 10285.
doi:10.1021/JP306788R
Supplementary Material
Calculated 1H and 13C NMR data, absolute energies, and
Cartesian coordinates of all computed structures and details of
PCM parameters are available on the Journal’s website.
[17] H. Mu¨ller-Starke, Thermische Reaktionen von (4H)-Isoxazol-5-on-
Derivaten und ESR-spektroskopische Untersuchungen an Radikalen
aus 4-Oximino-(4H)-Isoxazol-5-onen und strukturverwandten Hetero-
cyclen, Diplomarbeit 1979, Universita¨t Marburg, Marburg, Germany.
[18] A. Buß, Evaluation theoretischer Methoden zur Berechnung NMR-
chemischer Verschiebungen von Heterocyclen, Bachelorarbeit 2012,
Universita¨t Oldenburg, Oldenburg, Germany. In this thesis, the level of
theory employed in the current work (vb97xD/6-31G(d)//M06-2X/
6-311þþG(d,p)) has proved to reliably reproduce the ordering of the
chemical shifts.
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft, The
University of Queensland, the National Computing Infrastructure facility
(NC-MAS g01) sustained by the Australian Government, and the Center for
Scientific Computation at the Universita¨t Oldenburg.
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