Nitropyrazoles: XII. Transformations of the 4-methyl group in 1,4-dimethyl-3,5-dinitropyrazole and cyclization of the transformation products

Article abstract of DOI:10.1007/s11178-005-0374-9

A preparative procedure for the synthesis of 1,4-dimethyl-3,5- dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl-(dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5- dinitropyrazol-4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl-3,5- dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K₂CO₃ to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K₂CO₃ in acetonitrile; in the reaction with K₂CO₃ in ethanol, the 5-nitro group was replaced by ethoxy.

Full text of DOI:10.1007/s11178-005-0374-9

Russian Journal of Organic Chemistry, Vol. 41, No. 10, 2005, pp. 1507–1515. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 10, 2005,
pp. 1538–1546.
Original Russian Text Copyright © 2005 by Zaitsev, Dalinger, Starosotnikov, Kachala, Strelenko, Shkineva, Shevelev.
Dedicated to Full Member of the Russian Academy of Sciences
N.S. Zefirov on His 70th Anniversary
Nitropyrazoles: XII.* Transformations of the 4-Methyl Group
in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization
of the Transformation Products
A. A. Zaitsev, I. L. Dalinger, A. M. Starosotnikov, V. V. Kachala, Yu. A. Strelenko,
T. K. Shkineva, and S. A. Shevelev
Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia
e-mail: shevelev@mail.ioc.ac.ru
Received June 14, 2005
Abstract—A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-di-
methylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl-
(dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitro-
pyrazol-4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetalde-
hyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl-
3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with
K2CO3 to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-
4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-
acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenyl-
hydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of
K2CO3 in acetonitrile; in the reaction with K2CO3 in ethanol, the 5-nitro group was replaced by ethoxy.
Pyrazole derivatives are very important from the
practical viewpoint; the chemistry of pyrazoles has
been well documented, and various convenient methods
for the synthesis of these compounds have been de-
veloped [2]. On the other hand, there exists some
deficiency in general synthetic approaches to bicyclic
structures in which pyrazole ring is fused to other five-
membered aromatic heterocycles. Known examples
concerning preparation of such systems cannot be
regarded as universal, and synthesis of each type of bi-
cyclic compounds requires special selection of approp-
riate substituents and their introduction into pyrazole
ring or the second heterocycle with subsequent cyclo-
condensation [3].
methyl-3,5-dinitropyrazoles. It includes preliminary
modification of the 4-methyl group in 1-R-4-methyl-
3,5-dinitropyrazoles via reactions with electrophiles or
oxidants, followed by transformation of the modified
compounds into the target bicyclic products through
either intramolecular replacement of the nitro group
or its substitution or reduction and subsequent
cyclization.
The feasibility of the proposed scheme follows
from specific chemical properties of nitropyrazoles,
including their accessibility, high reactivity of the nitro
group in nucleophilic substitution processes, strong
activation of methyl group by the neighboring nitro
groups in reactions with electrophiles, and the pos-
sibility for further functionalization of the bicyclic
product via transformations of the remaining nitro
group [4]. Moreover, we previously showed [1] that
the nitro group in position 5 of 3(5)-nitropyrazoles is
much more reactive toward nucleophiles than the
3-nitro group. Therefore, the 5-nitro group should be
replaced with high selectivity both inter- and intra-
molecularly.
Our studies are aimed at developing universal syn-
thetic approaches to bicyclic structures in which pyr-
azole ring is fused to various five-membered O-, S-,
and N-heterocycles. We believe that such a general
approach may involve the use as starting compounds
only one type of substituted pyrazoles, namely 1-R-4-
* For communication XI, see [1].
1070-4280/05/4110-1507 © 2005 Pleiades Publishing, Inc.

ZAITSEV et al.
1508
Scheme 1.
Me
OEt OEt
CH(OEt)3, ZnCl2
MeNHNH2 ·HCl
Et2O, 40–50°C, 2 h
H2O, 70°C, 3 h
OEt
N
Me
EtO
OEt
N
Me
Me
III
II
O2N
Me
HNO3 (d = 1.5), concd. H2SO4
100°C, 6 h
N
NO2
N
Me
I, 50–55%
1H NMR spectrum of IV indicates trans configuration
of the exocyclic double bond. Iy should be noted that
this reaction is the first example of direct modification
of the methyl group in position 4 of pyrazole ring,
leading to formation of a new carbon–carbon bond.
The present article reports on the development of
a preparative procedure for the synthesis of 1,4-di-
methyl-3,5-dinitropyrazole (I) as the simplest and con-
venient model of 1-R-4-methyl-3,5-dinitropyrazoles,
purposeful transformation of the 4-methyl group in
compound I, and cyclization of the products thus
formed.
Scheme 2.
Ha
NMe2
Katritzky et al. [5] described the synthesis of com-
pound I by nitration of 1,4-dimethylpyrazole (II) with
a mixture of sulfuric and nitric acids. However, the
yield of dinitropyrazole I was poor (24%), and the
reactant ratio did not allow the reaction to be per-
formed on an enlarged scale under laboratory condi-
tions. By varying the reactant ratio, we succeeded in
selecting acceptable conditions for the nitration of
1,4-dimethylpyrazole (II), which (1) ensured prepara-
tion of dinitropyrazole I in a considerably larger yield
(50–55%, Scheme 1) and (2) made it possible to obtain
40–50 g of the product in a single run. The optimal
reactant ratio II–HNO3 (d = 1.5)–H2SO4 was 1:2:20
by volume. As starting compound for the synthesis of
1,4-dimethylpyrazole (II) we used commercially avail-
able 1-ethoxypropene (III) [6, 7] (Scheme 1).
O2N
(MeO)2CHNMe2, DMF
150°C, 1 h
Hb
N
I
NO2
N
Me
IV, 75%
We compared the reactivity of compound I and
some nitrotoluenes toward dimethylformamide di-
methyl acetal (see table). The results showed that the
activity of the 4-methyl group in pyrazole I is most
similar to that of the methyl group in 2,4-dinitro-
toluene [9].
Hydrolysis of enamine IV with hydrochloric acid
gave 1-methyl-3,5-dinitropyrazol-4-ylacetaldehyde
(V). The reaction of IV with sodium nitrite in con-
centrated hydrochloric acid involved both hydrolysis
and nitrosation; as a result, hydroxyimino(1-methyl-
3,5-dinitropyrazol-4-yl)acetaldehyde (VI) was obtain-
ed (Scheme 3).
We believed it reasonable to build up an enamine
fragment in position 4 of dinitropyrazole I by modif-
ication of the 4-methyl group and examine transforma-
tions of that fragment to obtain compounds capable of
unergoing intramolecular cyclization (i.e., intramolec-
ular substitution of the nitro group). Just the same
approach turned out to be successful in the synthesis
of benzo-fused heterocycles (benzisoxazoles and in-
dazoles) from 2,4,6-trinitrotoluene [8]. We found con-
ditions ensuring reaction of I with dimethoxymethyl-
(dimethyl)amine (N,N-dimethylformamide dimethyl
acetal) to produce enamine IV (Scheme 2). The 1H–1H
spin–spin coupling constant Jab = 13.2 Hz in the
It is known [10] that compounds like A are capable
of undergoing intramolecular nucleophilic substitution
of the nitro group to give benz[d]isoxazoles B under
basic conditions (Scheme 4). We anticipated that ana-
logous cyclization should also occur with oximes of
the pyrazole series, in which the hydroxyimino group
is adjacent to nitro group. By treatment of oxime VI
with potassium carbonate in ethanol we obtained hy-
droxypyrazolecarbonitrile VIII (Scheme 5). In keeping
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

NITROPYRAZOLES: XII.
1509
Scheme 3.
OCH
N
NMe2
O2N
O2N
O2N
CHO
N
NaNO2, concd. HCl
25°C, 5 h
HCl–H2O–CHCl3, 25°C
OH
NO2
N
N
N
NO2
NO2
N
N
Me
Me
Me
V, 69%
IV
VI, 94%
Scheme 4.
X
X
Base
–NO2
N
R
R
N
O
OH
NO2
A
B
Scheme 5.
OCH
O2N
CHO
O2N
O2N
CN
N
K2CO3, EtOH
OH
NO2
N
N
N
N
N
OH
O
N
N
Me
Me
Me
VI
VII
VIII, 39%
with published data [8], the reaction involves inter-
mediate formation of pyrazolo[4,3-d]isoxazole VII
which undergoes deformylation and opening of the
isoxazole ring by the action of a base. The position of
the hydroxy group in the pyrazole ring of VIII was
determined by the HMBC two-dimensional correlation
substitution of nitro group in compound VI occurs just
at position 5.
To avoid opening of isoxazole ring like in VII,
protection of the aldehyde group is commonly used.
Many derivatives of such aldehydes are stable in basic
medium, and they can be isolated and subjected to
isoxazole ring closure [8]. We synthesized derivatives
of hydroxyimino(pyrazolyl)acetaldehyde VI at the
formyl group, O-methyloxime IX and phenylhydra-
zone X, by reactions with O-methylhydroxylamine and
phenylhydrazine, respectively (Scheme 6). Treatment
of compound IX with potassium carbonate in ethanol
gave the corresponding 3-substituted 6-methyl-4-nitro-
pyrazolo[4,3-d]isoxazole (XI) (Scheme 7). The struc-
ture of XI was established as follows. The data of
1
technique, on the basis of long-range H–13C coupling
constants. In the HMBC spectrum of VIII, protons of
the N-methyl group showed the only cross peak with a
carbon atom whose signal is located at įC 159.27 ppm.
According to published data [11], this signal belongs
to the carbon atom attached to the hydroxy group
(the CNO2 carbon atom gives a broadened signal at
įC 150.46 ppm). Thus the COH carbon atom is closer
to the NCH3 group than CNO2, i.e., intramolecular
Reactivity of nitrotoluenes and 1,4-dimethyl-3,5-dinitropyrazole (I) toward dimethoxymethyl(dimethyl)amine
Temperature,
°C
Reaction
time, h
Excess of dimethoxymethyl- Yield of
Compound
Solvent
(dimethyl)amine, mol %
enamine, %
2,4,6-Trinitrotoluene
1,4-Dimethyl-3,5-dinitropyrazole
2,4-Dinitrotoluene
Toluene
DMF
DMF
DMF
DMF
20
24
01
02
09
26
000
150
200
100
000
70
75
99
91
86
Reflux
Reflux
Reflux
Reflux
2,6-Dinitrotoluene
2-Nitrotoluene
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

ZAITSEV et al.
1510
Scheme 6.
Ph
MeO
NH
N
N
OCH
PhNHNH2 ·HCl, EtOH
80°C, 1 h
NH2OMe, EtOH
80°C, 1 h
O2N
O2N
O2N
N
N
N
OH
NO2
OH
NO2
OH
NO2
N
N
N
N
N
N
Me
Me
Me
X, 89%
VI
IX, 98%
Scheme 7.
MeON
O2N
NOMe
O2N
N
K2CO3, EtOH, 80°C, 30 min
or 25°C, 8 h
OH
NO2
N
N
N
N
O
N
Me
Me
IX
XI, 65%
The structure of XI was also proved by X-ray anal-
ysis. These results will be reported elsewhere, but we
can note that the N–O bond in pyrazoloisoxazole XI is
appreciably longer than the corresponding bond in
substituted benz[d]isoxazole [13]: 1.443 and 1.411 Å,
respectively. This means that the N–O bond in XI is
weaker than in the benzo-fused analog.
elemental analysis and mass spectrometry (m/z 225,
M+) were consistent with the formula C7H7N5O4. The
1H NMR spectrum of compound XI contained only
three signals at į 8.23 (CH), 4.13 (NCH3), and
4.05 ppm (OCH3). On the basis of the HMBC spec-
1
trum (by long-range H–13C coupling constants) we
identified all 13C signals and proved that the nitro
group in position 5 rather than 3 in compound IX was
replaced, in keeping with our previous data [1]. In fact,
the HMBC spectrum of XI revealed two cross peaks
due to coupling between protons of the N-methyl
group and carbon nuclei with chemical shifts įC of
142.60 and 168.25 ppm; the latter carbon atom gives a
much stronger cross peak. The signal at įC 142.60 ppm
belongs to the carbon atom linked to nitro group
(a typical range of chemical shifts of pyrazole carbon
atoms attached to a nitro group is 140–155 ppm [12]).
In addition, this signal is strongly broadened, which
is also typical of quaternary carbon atoms linked to
a nitro group. Insofar as the correlation between the
NCH3 protons and the CNO2 carbon atom is consider-
ably weaker than that between NCH3 and CO, the
CNO2 carbon atom is more distant from the N-methyl
group than CO, and hence compound XI has structure
C rather than D.
Under similar conditions, the cyclization of phenyl-
hydrazone X afforded substituted 1,2,3-triazole XIII
instead of expected pyrazoloisoxazole XII (Scheme 8).
Obviously, compound XIII is formed via rearrange-
ment of XII. An analogous recyclization was recently
observed in the series of benz[d]isoxazoles [14]; how-
ever, in our case, it occurred much more readily, and
(unlike benzo-fused analog) intermediate pyrazolo-
isoxazole XII could not be isolated or even detected.
Obviously, the rate of its rearrangement is considerably
higher than the rate of formation. As we noted above,
the N–O bond in XI is weaker than the corresponding
bond in the benzo-fused analog. Undoubtedly, the N–O
bond in structurally related pyrazoloisoxazole XII is
also weakened, which facilitates its cleavage via intra-
molecular nucleophilic substitution at the isoxazole
nitrogen atom (Scheme 8).
According to the data of elemental analysis and
mass spectrometry (the mass spectrum contained the
molecular ion peak with m/z 286), compound XIII has
the composition C12H10N6O3. In the 1H NMR spectrum
of XIII, signal from the N-methyl group appeared at
į 3.77 ppm (cf. į 4.35 ppm for compound X; įǻ §
0.6 ppm). Protons in the N-methyl group of O-methyl-
oxime IX give a signal at į 4.33 ppm, while the corre-
NOMe
NOMe
O2N
N
O2N
4
3
3a
6a
N
Me
N
N
N
O
N
O
Me
C
D
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

NITROPYRAZOLES: XII.
1511
Scheme 8.
PhNH
N1'
N
Ph
O2N
N
5'
N2'
Ph
N
K2CO3, EtOH
80°C, 2 h or 25°C, 24 h
O2N
N
O2N
N3'
N
4'
H
3
N
N
4
OH
NO2
N
O
2N
5
OH
N
N1
Me
XIII, 45%
Me
Me
X
XII
sponding signal of pyrazolo[4,3-d]isoxazole XI is
located at į 4.13 ppm, i.e., the upfield shift is only
0.2 ppm. Compound VIII possessing a hydroxy group
in the pyrazole ring is characterized by a chemical shift
of the N-methyl protons of į 3.65 ppm, which is
tween the methyl protons and carbon atom linked to
the nitro group was present (a broadened signal from
that carbon atom was located at įC 149.6 ppm). These
data indicate that, like in compound IX, just the nitro
group in position 5 of pyrazole X is replaced via intra-
molecular nucleophilic attack.
1
similar to that found for XIII. The H NMR spectrum
recorded from a solution of XIII in DMSO-d6 lacked
signal from NH proton, which is typical of phenylhy-
drazones (į 10.70 ppm for compound X). In CDCl3,
the OH proton characteristically gives a broadened
signal at į 9.5–10 ppm.
By reaction of pyrazolylacetaldehyde V with ben-
zenediazonium chloride we obtained 2-(1-methyl-3,5-
dinitropyrazol-4-yl)-2-phenylhydrazonoacetaldehyde
(XIV) (Scheme 9) as a result of azo coupling at the
activated methylene group. Like oximes derived from
aromatic ketones having a nitro group in the ortho
position (structure A in Scheme 4), the corresponding
arylhydrazones are also capable of undergoing intra-
molecular substitution of the ortho-nitro group by
the action of bases to produce N-arylindazoles [17].
An analogous intramolecular cyclization might be ex-
pected for hydrazone XIV with formation of pyrazolo-
[3,4-c]pyrazole XV. However, heating of hydrazone
XIV with potassium carbonate in ethanol resulted in
replacement of the 5-nitro group by ethoxy to give
compound XVI (Scheme 9). Obviously, the system
EtOH–K2CO3 is a stronger nucleophile than the ter-
minal hydrazone fragment (PhNH) in the presence of
K2CO3 as deprotonating agent. In the latter case,
nucleophilic substitution also occurs at the 5-position
In the 13C spectrum of compound XIII in DMSO-d6,
the C5 (COH) signal appears at įC 151.8 ppm, which is
consistent with published data [15]. The chemical shift
of C5 in pyrazolo[4,3-d]isoxazole XI (see above) is
168.25 ppm. The 15N NMR spectrum of XIII contains
only two signals from the triazole ring, at įN –69.44
(N1') and –133.36 ppm (N2') (relative to CH3NO2); the
signals were assigned on the basis of the HSQC two-
dimensional correlation spectrum using long-range
1H–15N coupling constants (cf. [16]). No signal from
N3' was detected. An analogous pattern was observed
in [14] for a benzo-fused analog. We also recorded the
HMBC spectrum of compound XIII, which showed
a correlation between the methyl protons and carbon
atom bearing the hydroxy group; no cross peak be-
Scheme 9.
O2N
N
CHO
4
K2CO3, MeCN
80°C, 2 h
3
3a
6a
N
OCH
N
N
O2N
O2N
CHO
NNHPh
Me
Ph
XV, 75%
PhN2Cl–, HCl, 0–5°C
N
N
NO2
NO2
OCH
N
N
O2N
NNHPh
Me
Me
K2CO3, EtOH
80°C, 1 h
V
XIV, 73%
N
OEt
N
Me
XVI, 56%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

ZAITSEV et al.
1512
of the pyrazole ring. This follows, e.g., from the fact
below 35°C. Nitric acid (d = 1.5 g/cm3), 50 ml, was
added to the mixture under vigorous stirring at 30–
40°C. The mixture was vigorously stirred for 6 h at
90–100°C, cooled, and poured into 1 kg of ice water.
Air was bubbled through the resulting suspension on
slight heating to remove nitrogen oxide, the mixture
was extracted with ethyl acetate (3×400 ml), the ex-
tract was washed with aqueous ammonia until neutral
reaction and dried over Na2SO4, the solvent was dis-
tilled under reduced pressure, and the solid residue was
recrystallized from ethanol. Yield 25.6 g (55.1%),
colorless crystals, mp 107–108°C (from EtOH); pub-
lished data [5]: mp 101–102°C. IR spectrum, Ȟ, cm–1:
1
that the H–13C HMBC spectrum contains cross peaks
due to correlation of the NCH3 and OCH2 protons with
the same carbon nuclei while no other cross peaks
for the NCH3 protons are observed. In addition, the
NOESY spectrum revealed coupling between the
NCH3 and OCH2 protons, which is possible only when
the ethoxy group is located at position 5 of the pyra-
zole ring. We succeeded in effecting intramolecular
cyclization of hydrazone XIV to expected 6-methyl-4-
nitro-1-phenylpyrazolo[3,4-c]pyrazole (XV) by car-
rying out the reaction with K2CO3 in acetonitrile in-
stead of ethanol (Scheme 9). In the NOESY spectrum
of XV we observed correlation between the NCH3
protons and ortho-protons in the benzene ring on N1;
this means that the nitro group in position 5 was
replaced via nucleophilic attack by the PhNH group.
The structure of compound XV was also proved by
X-ray analysis (the crystallographic data will be
reported elsewhere).
1
1532, 1524, 1328, 1316 (NO2). H NMR spectrum
(DMSO-d6), į, ppm: 4.23 s (3H, NCH3), 2.57 s
(3H, CH3). 13C NMR spectrum (DMSO-d6), įC, ppm:
150.38 (C3), 144.02 (C5), 114.30 (C4), 42.52 (CH3),
9.64 (NCH3). Mass spectrum: m/z 186 [M]+. Found, %:
C 32.34; H 3.20; N 29.92. C5H6N4O4. Calculated, %:
C 32.27; H 3.25; N 30.10.
Thus transformation of the 4-methyl group in
1,4-dimethyl-3,5-dinitropyrazole (I) with the use of di-
methylformamide dimethyl acetal leads to compounds
capable of undergoing intramolecular cyclization (intra-
molecular substitution of the nitro group) to afford
bicyclic systems consisting of two five-membered
aromatic heterocycles or products of their subsequent
transformations. In all cases, only the 5-nitro group is
replaced. In the subsequent communications we will
report on other ways of transformation of the 4-methyl
group in compound I with a view to obtain systems
containing a pyrazole ring fused to five-membered
aromatic heterocycles.
(E)-N,N-Dimethyl-2-(1-methyl-3,5-dinitropyr-
azol-4-yl)ethenylamine (IV). 1,4-Dimethyl-3,5-di-
nitropyrazole (I), 30.0 g (0.161 mol), was dissolved in
250 ml of DMF, 55 ml (0.414 mol) of dimethoxy-
methyl(dimethyl)amine was added, and the mixture
was heated to the boiling point and kept for 1 h at that
temperature. The mixture was cooled, the solvent was
distilled off under reduced pressure, and the solid
residue was recrystallized from ethanol. Yield 29.1 g
(74.8%), dark green crystals, mp 114–115°C (from
EtOH). IR spectrum, Ȟ, cm–1: 1552, 1380 (NO2).
1H NMR spectrum (DMSO-d6), į, ppm: 7.93 d (1H,
Hb, J = 13.2 Hz), 5.62 d (1H, Ha, J = 13.2 Hz), 4.19 s
(3H, NCH3), 2.99 s [6H, N(CH3)2]. 13C NMR spec-
trum, įC, ppm: in DMSO-d6: 151.62 (CHb), 146.90
(C3), 139.43 (C5), 120.19 (C4), 80.00 (CHa), 43.28
(NCH3); in CDCl3: 151.71 (CHb), 147.70 (C3), 139.56
(C5), 120.71 (C4), 81.04 (CHa), 43.42 (NCH3), 40.78 br
[N(CH3)2]. Mass spectrum: m/z 241 [M]+. Found, %:
C 39.60; H 4.53; N 28.43. C8H11N5O4. Calculated, %:
C 39.84; H 4.60; N 29.04.
EXPERIMENTAL
The IR spectra were recorded on a Specord M-82
spectrometer from samples prepared as KBr pellets
or solutions in CHCl3 (c = 0.01 mol/l, d = 3 mm). The
1H and 13C NMR spectra were recorded on Bruker
WM-250, Bruker AC-300, and Bruker AC-500 instru-
ments. The chemical shifts were measured relative to
tetramethylsilane. The mass spectra (electron impact,
70 eV) were obtained on a Kratos MS-30 mass spec-
trometer. The progress of reactions and the purity of
products were monitored by TLC on Silufol UV-254
plates.
(1-Methyl-3,5-dinitropyrazol-4-yl)acetaldehyde
(V). Compound IV, 20.0 g (0.083 mol), was dissolved
in 200 ml of chloroform, 300 ml of 2 M hydrochloric
acid was added, the mixture was stirred for 1 h, and the
aqueous phase was separated and extracted with ethyl
acetate (3×100 ml). The extracts were combined with
the organic phase and dried over Na2SO4, and the
solvent was distilled off under reduced pressure. The
oily residue was crystallized from carbon tetrachloride.
Yield 12.3 (69.3%), light brown solid substance,
1,4-Dimethyl-3,5-dinitropyrazole (I). 1,4-Dimeth-
ylpyrazole [6, 7], 25.0 ml (d = 0.96 g/cm3, 0.250 mol),
was added dropwise under stirring to 500 ml of con-
centrated sulfuric acid, maintaining the temperature
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

NITROPYRAZOLES: XII.
1513
mp 89–90°C (from CCl4). IR spectrum, Ȟ, cm–1: 1724
75 ml of ethanol, the mixture was stirred for 30 min,
and 5.00 g (0.021 mol) of compound VI was added.
The mixture was heated for 1 h under reflux and
cooled, the solvent was distilled off under reduced
pressure, the solid residue was treated with water, and
the undissolved material was filtered off, washed with
cold water, and dried. Yield 5.48 g (97.9%), light yel-
low crystalline substance, mp 85–86°C (from CHCl3–
CCl4, 1:1). IR spectrum, Ȟ, cm–1: 3360 br (OH);
1
(C=O); 1528, 1344 (NO2). H NMR spectrum
(DMSO-d6), į, ppm: 9.69 s (1H, CHO), 4.33 s (2H,
CH2), 4.28 s (3H, CH3). 13C NMR spectrum
(DMSO-d6), įC, ppm: 196.84 (CHO), 150.60 (C3),
144.39 (C5), 109.57 (C4), 42.59 (CH3), 38.31 (CH2).
Mass spectrum: m/z 186 [M – CO]+. Found, %:
C 33.73; H 2.80; N 25.96. C6H6N4O5. Calculated, %:
C 33.65; H 2.82; N 26.16.
1
1704 (C=O); 1536, 1336 (NO2). H NMR spectrum
2-Hydroxyimino-2-(1-methyl-3,5-dinitropyrazol-
4-yl)acetaldehyde (VI). A solution of 17.5 g
(0.254 mol) of sodium nitrite in 100 ml of water was
added dropwise over a period of 1.5–2 h at room tem-
perature to a solution of 30.0 g (0.124 mol) of com-
pound IV in 300 ml of concentrated hydrochloric acid.
The mixture was stirred for 3 h and was left overnight.
It was then diluted with 1000 ml of water and stirred
for 30 min. The precipitate was filtered off, washed
with cold water (3×100 ml), and dried. Yield 28.3 g
(93.6%), light yellow crystals, mp 163–167°C
(decomp.). IR spectrum, Ȟ, cm–1: 3265 br (OH);
(DMSO-d6), į, ppm: 12.75 s (1H, OH), 8.13 s (1H,
CH), 4.32 s (3H, NCH3), 3.74 s (3H, OCH3). 13C NMR
spectrum (DMSO-d6), įC, ppm: 149.00 (C3), 145.80
(C=NOH), 143.18 (C5), 140.90 (C=NOMe), 104.31
(C4), 62.27 (OCH3), 42.31 (NCH3). Mass spectrum:
m/z 272 [M]+. Found, %: C 31.96; H 2.77; N 28.01.
C7H8N6O6. Calculated, %: C 30.89; H 2.96; N 30.88.
2-Hydroxyimino-2-(1-methyl-3,5-dinitropyrazol-
4-yl)acetaldehyde phenylhydrazone (X). Compound
VI, 2.00 g (8.2 mmol), was dissolved in 30 ml of
ethanol, 1.19 g (8.2 mmol) of phenylhydrazine hydro-
chloride was added, and the mixture was heated for
1 h under reflux. It was then cooled and poured into
300 ml of water, and the precipitate was filtered off,
washed with water, and dried. Yield 2.44 g (89.0%),
orange solid substance, mp 178–179°C. IR spectrum,
Ȟ, cm–1: 3320 br (NH, OH); 1528, 1336 (NO2).
1H NMR spectrum (DMSO-d6), į, ppm: 12.00 s (1H,
OH), 10.58 s (1H, NH), 7.75 s (1H, CH), 7.15 br.m
(2H, m-H), 6.72 br.m (3H, o-H, p-H), 4.32 s (3H,
CH3). Mass spectrum: m/z 333 [M]+. Found, %:
C 42.70; H 3.40; N 28.70. C12H11N7O5. Calculated, %:
C 43.25; H 3.33; N 29.42.
1
1704 (C=O); 1536, 1336 (NO2). H NMR spectrum
(DMSO-d6), į, ppm: 14.00 s (1H, OH), 9.73 s
(1H, CH), 4.33 s (3H, CH3). 13C NMR spectrum
(DMSO-d6), įC, ppm: 188.76 (CHO), 149.03 (C3),
146.29 (C=NOH), 143.44 (C5), 102.14 (C4), 42.52
(CH3). Mass spectrum: m/z 243 [M]+. Found, %:
C 29.61; H 2.04; N 28.62. C6H5N5O6. Calculated, %:
C 29.64; H 2.07; N 28.80.
5-Hydroxy-1-methyl-3-nitropyrazole-4-carbo-
nitrile monohydrate (VIII). Compound VI, 1.00 g
(4.1 mmol), was dissolved in 20 ml of ethanol, 0.57 g
(4.1 mmol) of potassium carbonate was added, and the
mixture was stirred for 15 h at room temperature. The
mixture was poured into 100 ml of water, hydrochloric
acid was added to a weakly acidic reaction, and the
precipitate was filtered off, washed with cold water
(2×20 ml), and dried. Yield 0.27 g (39.0%), light
yellow substance, mp 70–80°C (loss of H2O), 215–
220°C (decomp.). IR spectrum, Ȟ, cm–1: 3460 br (OH);
6-Methyl-4-nitropyrazolo[4,3-d]isoxazole-3-
carbaldehyde O-methyloxime (XI). Compound IX,
2.00 g (7.3 mmol), was dissolved in 30 ml of ethanol,
1.01 g (7.3 mmol) of potassium carbonate was added,
and the mixture was heated for 30 min under reflux. It
was then cooled, the solvent was distilled off under
reduced pressure, and the solid residue was treated
with 150 ml of water. The undissolved material was
filtered off, dried, and recrystallized from ethanol.
Yield 1.08 g (65.3%), yellow crystalline substance,
mp 138–140°C (from EtOH). IR spectrum, Ȟ, cm–1:
1
2248 (CŁN); 1540, 1352 (NO2). H NMR spectrum
(DMSO-d6), į, ppm: 3.64 s (3H, CH3). 13C NMR spec-
trum (DMSO-d6), į, ppm: 159.28 (C5), 150.48 (C3),
112.32 (CN), 69.52 (C4), 34.36 (CH3). Mass spectrum:
m/z 168 [M]+. Found, %: C 32.34; H 3.27; N 28.90.
C5H6N4O4. Calculated, %: C 32.27; H 3.25; N 30.10.
1
1544, 1336 (NO2). H NMR spectrum (acetone-d6), į,
ppm: 8.23 s (1H, CH), 4.13 s (3H, NCH3), 4.05 s (3H,
OCH3). 13C NMR spectrum (acetone-d6), įC, ppm:
168.25 (C6a), 150.42 (C3), 142.60 (C4), 138.02
(C=NOMe), 103.33 (C3a), 63.72 (OCH3), 37.50
(NCH3). IR spectrum, Ȟ, cm–1: 1544, 1336 (NO2).
Mass spectrum, m/z: 225 [M]+, 227 [M + 2H]+. Found,
2-Hydroxyimino-2-(1-methyl-3,5-dinitropyrazol-
4-yl)acetaldehyde O-methyloxime (IX). O-Methyl-
hydroxylamine hydrochloride, 1.89 g (0.023 mol), and
sodium hydroxide, 0.82 g (0.021 mol), were added to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 10 2005

ZAITSEV et al.
1514
%: C 37.54; H 3.24; N 30.72. C7H7N5O4. Calculated,
%: C 37.34; H 3.13; N 31.10.
(1.57 mmol), was dissolved in 20 ml of acetonitrile,
0.22 g (1.57 mmol) of potassium carbonate was added,
and the mixture was heated for 2 h under reflux. The
mixture was cooled, poured into 150 ml of water, and
neutralized with hydrochloric acid, and the precipitate
was filtered off, washed with water, dried and purified
by column chromatography. Yield 0.32 g (75.1%),
light brown substance, mp 241–243°C. IR spectrum, Ȟ,
1-Methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-
yl)pyrazol-5-ol (XIII). Compound X, 1.00 (3.0 mmol),
was dissolved in 15 ml of ethanol, 0.41 g (3.0 mmol)
of potassium carbonate was added, and the mixture
was heated for 2 h under reflux. It was then cooled,
poured into 150 ml of water, hydrochloric acid was
added to a weakly acidic reaction, and the precipitate
was filtered off, washed with water, dried, and recrys-
tallized from methanol. Yield 0.39 (45.4%), yellow
crystalline substance, mp 193–194°C (from MeOH).
IR spectrum (CHCl3), Ȟ, cm–1: 3220 br (OH); 1528,
1352 (NO2). 1H NMR spectrum, į, ppm: in DMSO-d6:
8.22 s (1H, CH), 8.08 d (2H, o-H), 7.57 t (1H, p-H),
7.45 t (2H, m-H), 3.75 s (3H, CH3); in CDCl3: 9.70 br.s
(1H, OH), 8.50 s (1H, CH), 7.98 d (2H, o-H), 7.52 t
(1H, p-H), 7.42 t (2H, m-H), 3.87 s (3H, NCH3).
13C NMR spectrum (DMSO-d6), įC, ppm: 151.76 (C5),
149.57 (C3), 139.20 (Ci), 138.57 (C4'), 136.81 (C5'),
129.70 (Cm), 127.72 (Cp), 118.45 (Co), 88.72 (C4),
34.73 (CH3). 15N NMR spectrum (DMSO-d6, MeNO2),
įN, ppm: –69.44 (N1'), –111.40 (N2), –133.36 (N2'),
–204.95 (N1). Mass spectrum: m/z 286 [M]+. Found,
%: C 49.69; H 3.48; N 28.79. C12H10N6O3. Calculated,
%: C 50.35; H 3.52; N 29.36.
1
cm–1: 1704 (C=O); 1532, 1364 (NO2). H NMR spec-
trum (DMSO-d6, 80°C), į, ppm: 10.16 s (1H, CHO),
7.79 d (2H, o-H), 7.63 t (2H, m-H), 7.60 t (1H, p-H),
3.91 s (3H, CH3). 13C NMR spectrum (DMSO-d6,
80°C), įC, ppm: 183.52 (CHO), 149.55 (C6a), 140.96
(C4), 136.84 (C3), 135.99 (Ci), 129.33 (Cm, Cp), 124.49
(Co), 108.04 (C3a), 38.30 (CH3). Mass spectrum:
m/z 271 [M]+. Found, %: C 52.43; H 3.47; N 25.33.
C12H9N5O3. Calculated, %: C 53.14; H 3.34; N 25.82.
2-(5-Ethoxy-1-methyl-3-nitropyrazol-4-yl)acet-
aldehyde phenylhydrazone (XVI). Compound XIV,
0.50 g (1.57 mmol), was dissolved in 20 ml of ethanol,
0.22 g (1.57 mmol) of potassium carbonate was added,
and the mixture was heated for 1 h under reflux. The
mixture was cooled, poured into 150 ml of water, and
neutralized with hydrochloric acid. The precipitate was
filtered off, washed with water, and dried. Yield 0.28 g
(56.2%), bright yellow substance, mp 198–200°C.
IR spectrum, Ȟ, cm–1: 3256 (NH); 1684 (C=O); 1540,
2-(1-Methyl-3,5-dinitropyrazol-4-yl)acetalde-
hyde phenylhydrazone (XIV). A solution of 0.70 g
(10.1 mmol) of sodium nitrite in 3 ml of water was
added under stirring to a mixture of 1.22 g (9.4 mmol)
of aniline hydrochloride, 4 ml of concentrated hydro-
chloric acid, and 4 ml of water, maintaining the tem-
perature at 0–5°C. The mixture was stirred for 5 min,
and sodium acetate was added to pH 5, and a solu-
tion of 2.00 g (9.3 mmol) of compound V in 45 ml of
ethanol was added at 5°C. The mixture was stirred
for 1.5 h and poured into 400 ml of water, and the
precipitate was filtered off, washed with cold water,
and dried. Yield 0.74 g (73.0%), dark orange solid,
mp 173–175°C. IR spectrum, Ȟ, cm–1: 3244 (NH);
1
1344 (NO2). H NMR spectrum (DMSO-d6), į, ppm:
10.75 s (1H, NH), 9.61 s (1H, CH), 7.39 d (2H, o-H),
7.32 t (2H, m-H), 7.05 t (1H, p-H), 4.05 q (2H, CH2),
3.81 s (3H, NCH3), 1.28 t (3H, CH3). 13C NMR spec-
trum (DMSO-d6), įC, ppm: 189.03 (CHO), 152.05
(C5), 150.32 (C3), 142.89 (C=NNHPh), 132.68 (Ci),
129.16 (Cm), 122.82 (Cp), 114.71 (Co), 88.30 (C4),
68.92 (CH2), 35.11 (NCH3), 14.33 (CH3). Mass spec-
trum: m/z 317 [M]+. Found, %: C 52.67; H 4.79;
N 21.77. C14H15N5O4. Calculated, %: C 52.99; H 4.76;
N 22.07.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-33097).
1
1660 (C=N); 1548, 1528, 1348, 1332 (NO2). H NMR
spectrum (DMSO-d6), į, ppm: 10.88 s (1H, NH), 9.56 s
(1H, CH), 7.35 m (4H, o-H, m-H), 7.08 t (1H, p-H),
13
4.42 s (3H, CH3). C NMR spectrum (DMSO-d6), įC,
REFERENCES
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m/z 318 [M]+. Found, %: C 45.50; H 3.21; N 26.14.
C12H10N6O5. Calculated, %: C 45.29; H 3.17; N 26.41.
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