Synthesis and comparison of the reactivity of 3,4,5-1H-trinitropyrazole and Its N-methyl derivative

Article abstract of DOI:10.1002/jhet.1026

3,4,5-Trinitro-1H-pyrazole (1) has been obtained via nitration of 3,5-dinitropyrazole with mixture of sulfuric and nitric acids. Compound 1 reacts with excess ammonia and aliphatic amines, in the presence of bases with NH-azoles, phenols, thiols, and trif

Full text of DOI:10.1002/jhet.1026

Month 2013
Synthesis and Comparison of the Reactivity of
3,4,5‐1H‐Trinitropyrazole and Its N‐Methyl Derivative
a
a
a
*
Igor L. Dalinger, Irina A. Vatsadze, Tatyana K. Shkineva,
Galina P. Popova,a Svyatoslav A. Shevelev,a and Yuliya V. Nelyubinab
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
119991, Leninsky pr., 47, Moscow, Russia
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian
Academy of Sciences, 119991, Vavilov Str., 28, Moscow, Russia
*
E-mail: dalinger@ioc.ac.ru
Received December 17, 2010
DOI 10.1002/jhet.1026
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
3,4,5‐Trinitro‐1H‐pyrazole (1) has been obtained via nitration of 3,5‐dinitropyrazole with mixture of
sulfuric and nitric acids. Compound 1 reacts with excess ammonia and aliphatic amines, in the presence
of bases with NH‐azoles, phenols, thiols, and triflouroethanol at mild conditions in water. All these reactions
occur as the nucleophilic substitution of the nitro‐group at position 4 in 1 affording 4‐R‐3,5‐dinitropyrazoles.
The product of methylation of 1, N‐methyl‐3,4,5‐trinitropyrazole (4), also reacts with thiols, phenols,
oximes, ammonia, amines, and NH‐azoles. The reactions proceed with high yields but nucleophilic
substitutions in these cases occur regioselectively at position 5 in 4 to afford 5‐R‐3,4‐dinitropyrazoles.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
5‐amino‐3,4‐dinitropyrazole by the mixture of 90% H2O2
and concentrated sulfuric acid in dichloroethane; (ii) via the
diazotation of 5‐amino‐3,4‐dinitropyrazole by sodium nitrite
in 20% sulfuric acid; (iii) and by the nitration of 3,5‐
dinitropyrazole with the mixture of sulfuric and nitric acids
in 60% oleum. In our independent work, TNP was synthe-
sized by the oxidation of 5‐amino‐3,4‐dinitropyrazole but
with the mixture of 84% H2O2 in concentrated sulfuric
acid [10]. Later, Shreeve et al. obtained TNP via the
oxidation of 4‐amino‐3,5‐dinitropyrazole with the mixture
of 30% H2O2 and concentrated sulfuric acid [11]. Because
of all these publications, such an interesting object as TNP
became available for the researchers.
As a part of our ongoing study on nitropyrazoles, it
appeared very interesting to investigate the nucleophilic sub-
stitution in TNP. Herve etal. found that under the action of
ammonia and alkali TNP could undergo the nucleophilic sub-
stitution of 4‐nitro group, although they pointed out “the nitro
at C4 is therefore strongly linked to the ring so that drastic
conditions are required to provoke its displacement” [9]. It
is well known, however, that the twist of aromatic nitro group
in respect to the appropriate ring (which was established in [9]
for the TNP and its anion) accelerates the substitution reaction
due to easier formation of the ipso‐σ‐complex between
Nitropyrazoles and dinitropyrazoles are widely used in
organic synthesis including the synthesis of valuable
biologically active compounds. Effective methods of synthe-
sis 3,4‐dinitropyirazoles and 3,5‐dinitropyirazoles by direct
acid nitration, as well as N‐nitropyrazole N→C rearrangement
in combination with detailed methods of a cycle func-
tionalization based on nucleophilic NO2‐group replacement,
make this type of pyrazoles exclusively attractive as starting
compounds for the synthesis of a wide range of not easily
accessible nitropyrazole derivatives [1–4].
In our previous works [5–8], it was shown that 3,4‐
dinitropyrazoles and 3,5‐dinitropyrazoles react with S‐,
N‐, and O‐nucleophiles to form product of regiospecific
substitution of 3‐nitro or 5‐nitro group, respectively.
The selectivity of substitution was found to depend on
the mutual arrangement of the nitro‐substituents at the
heterocyclic core.
Recently, Herve et al. synthesized N‐unsubstituted
pyrazole which has the nitro groups at all three ring
carbon atoms, i.e., 3,4,5‐trinitro‐1H‐pyrazole (TNP, 1) [9].
In this work, TNP was obtained using three approaches:
(i) through the oxidation of 4‐amino‐3,5‐dinitropyrazole or
© 2013 HeteroCorporation

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
Scheme 1
nucleophile and nitro arene. This stage was found to be the
rate‐determining one in substitution reactions in nitro hetero-
cycles and hexanitrobenzene [12].
different basicity (see Scheme 1) including such a weak
base (pKBH+ = 3.23 [18]) as 4‐amino‐1,2,4‐triazole (prod-
uct 3c, see Scheme 1) [19].
To shed a light on the problems mentioned above, the
more thorough study on the reactivity of TNP and its
simple N‐methylated analog (1‐methyl‐3,4,5‐trinitropyrazole,
MTNP) was initiated. This article summarizes and extends
our preliminary results on the nucleophilic substitution in
TNP [13,14] and MTNP. In addition to the synthetic part,
the article discusses the data of X‐ray single crystal studies
of key products and intermediates.
The structure of TNP 1 and its salt 3c (Fig. 1) was
established by X‐ray diffraction analysis (XRD) of their
single crystals (vide infra).
N‐Methyl‐3,4,5‐trinitropyrazole (MTNP, 4) was synthe-
sized [20] with 95% yield through the methylation of 1
with dimethylsulfate in the presence of NaHCO3; the very
mild conditions of this reaction—20°C, water—should be
stressed here (Scheme 2). The structure of 4 was confirmed
by XRD (Fig. 2, vide infra).
XRD study of TNP, its N‐aminotriazole salt 3c, MTNP,
and ammonium salt of 4‐amino‐3,5‐dinitropyrazole (5a)
[21]. In contrast to the crystallographic data reported by
RESULTS AND DISCUSSION
Herve [9], trinitropyrazole 1 (Fig. 1) crystallizes with three
independent molecules in an asymmetric unit [22]. In all
cases, the geometric parameters of the pyrazole ring fall
into the ranges typical for this class of compounds and are
close to the calculated ones for TNP [23], but the
disposition of the nitro groups in respect to the heterocycle
ring is significantly different. Thus, the twist angle of the
central nitro group in the independent species is 82.5(1)°,
63.8(1)°, and 69.5(1)°. The same value for the moiety N(3)
O(1)O(2) is 0.9(1)°, 14.8(1)°, and 9.7(1)°, and that for the
third nitro group is 2.7(1)°, 7.5(1)°, and 7.7(1)°,
respectively. The salt 3c exhibits the similar tendency: the
The synthesis of TNP, its salts, and MTNP. TNP 1 was
synthesized using the nitration of 3,5‐dinitropyrazole (2)
by the mixture of concentrated nitric and sulfuric acids
(Scheme 1) [15]. Such a mixture is usually being
used forthe transformation of 3(5)‐nitropyrazole into
3(5),4‐dinitropyrazole [16].
Trinitropyrazole 1 is a strong NH‐acid (pKa20°C = 0.05,
H2O, spectrophotometry [17]) being highly soluble in wa-
ter and many typical organic solvents such as ether,
ethylacetate, dioxane, THF, alcohols, acetonitrile, DMF,
and DMSO. Such high acidity makes possible the forma-
tion of salts of 1 with a wide variety of bases possessing
Figure 1 General view of the compound TNP 1 (left) and its salt 3c (right) in representation of atoms via thermal ellipsoids at 50% probability level.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
Scheme 2
for the nitro groups are 10.7(1)°, 69.6(1)°, and 10.2(1)°,
respectively. The nitro groups also participate in the forma-
tion of various intermolecular O···O interactions with the
corresponding interatomic separation being as small as
2.917(1) Å. As in the case of the 1 and 3, a number of
contacts of the O···π and C H···O types also contribute to
the formation of the 3D‐framework.
According to the XRD data (Fig. 3), the substituents in
NH4‐5a (synthesis vide infra) are nearly coplanar with the
pyrazole cycle—the trend that was previously observed for
the 1H‐pyrazole analog and its crystallosolvate with DMSO
[24]. Thus, the twist angle for the nitro groups N(3)O2 and N
(5)O2 in NH4‐5a is 3.5(1)° and 1.8(1)°, respectively [4.0(1)°
and 8.8(1)° in the case of the second independent moiety],
while for NH2 it is equal to 4.0(1)° and 4.6(1)°. Such a
disposition is, apparently, ensured by the intramolecular
interactions—the hydrogen bonds N(4) H(4NA)···O(5) and
N(4) H(4NB)···O(2) [N···O 2.836(1)–2.850(1) Å, NHO 118
(1)–122(1)°]. The groups NH2 also participate in formation
of intermolecular H‐bonds N(4) H(4NA)···O(5A) [N···O
2.934(1)–3.027(1) Å, NHO 156(1)–161(1)°], which assem-
ble the independent anions into dimers. The latter are
involved in the H‐bonds with cations [N···N 2.889(1)–2.933
(1) Å, NHN 166(1)–179(2)°; N···O 2.960(1)–3.044(1)
Å, NHO 125(1)–157(1)°] and water molecules [N···O 3.100
(1)–3.128(1) Å, NHO 139(1)–153(2)°; O···O 3.000(1)–3.213
(1) Å, OHO 138(1)–153(1)°] leading to the formation of the
H‐bonded 3D‐network. The latter is completed by the interac-
tions between the nitro groups; the smallest O···O distance
being 2.941(1) Å.
corresponding twist angle is 11.5(1)°, 55.5(1)°, and 12.9(1)°
in the case of the nitro groups at the atoms C1, C2, and C3.
Apart from the differences in the twist angles of the nitro
groups, comparing the TNP 1 and its salt 3c shows the
variation in the geometry of the central cycle. The greatest
difference [0.014(2) Å] is observed for the bond N N, which
is longer in the case of the salt, apparently, due to the forma-
tion of the strong H‐bond with its counter ion partner. In a
crystal of 1, each molecule of TNP forms only one H‐bond
of the intermediate strength; the latter is N(1) H(1)···N(2)
between the neighboring independent molecules [N···N
2.967(1)–3.059(1) Å, NHN 161(1)–173(1)°]. In a crystal of
3c, the cation is involved in the formation of two H‐bonds:
N(9) H(9NB)···N(1) [N···N 3.064(1) Å, NHN 156(2)°] and
N(7) H(7N)···N(2) [N···N 2.788(1) Å, NHN 179(1)°], whose
action together lead to the greater perturbation of the TNP
moiety than the corresponding H‐bonds in 1 do. The
resulting H‐bonded chains hold together by means of N
(9) H(9NA)···N6 H‐bond [N···N 3.264(1) Å, NHN 154(2)°]
between cations as well as of various contacts between the
nitro groups with the distance O···O as small as 2.940(1) Å.
The smallest intermolecular O···O distance in 1 is 2.912(1)
Å with the independent species being different in a type
and a number of interactions they are involved in. The
formation of the three‐dimensional (3D)‐framework in the
two crystals is accomplished by numerous O···π (1 and 3c)
and C H···O (3c) contacts.
Nucleophilic substitution in TNP. On studying the
reactivity of 1, we have found that TNP exhibits unusual
behavior in the reactions with nucleophiles. It readily
(water, room temperature) reacts with an excess of
ammonia [25] and aliphatic amines to form products 5a–h,
which result from the regiospecific substitution of a nitro
group at position 4 in starting TNP (Scheme 3). The full
Taking into account that the twist angle of the central NO2
group in the sodium salt of TNP is markedly bigger (82°) [9]
than that in 3c, the degree of this twist seems to depend on
the nature of a counter ion: in the case of Na+, which is
a rather small cation and cannot be involved (in contrast
to 3c) in the H‐bonding with the TNP moiety, the twist of
the group 4‐NO2 is more pronounced. One can assume that
in solutions of TNP salts, where cations and anions are
separated by the solvent molecules, the twist angle for this
group is more than 80°; hence, there is no conjugation
between the moiety 4‐NO2 and the pyrazole cycle, while
it is definitely not the case of the nitro groups 3‐NO2 and
5‐NO2 in both the salt 3c and that with sodium cation [9]
as well as in TNP itself.
The XRD investigation of MTNP 4 (Fig. 2) showed that
its molecular geometry (well reproduced in the recent
quantum chemical investigation of MTNP [23]) is close
to that in TNP 1 and its salt 3. In particular, the twist angles
Figure 2 General view of MTNP 4 in representation of atoms via thermal
ellipsoids at 50% probability level.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
8 and 9 (see Scheme 3). The reactions proceed in water
at room temperature in the presence of two equivalents
of NaOH, which means that TNP reacts with RO‐ and
RS‐anions in its own anionic form. The phenols with strong
electron‐withdrawing groups such nitro or cyano group do
not react with TNP at all under these conditions. In the case
of O‐nucleophiles, the full conversion is achieved after 10 h.
It should be noted that TNP itself is easily hydrolyzed even
in the presence of NaHCO3 [29] forming disodium salt 10
(see Scheme 2).
Independently on their nature, the thiols react with TNP
considerably faster them O‐nucleophiles, and the reactions
accomplish in 3 h. The products 8a–f and 9a–f were formed
as simply isolable solids after acidifying the reaction mixture
by 20% H2SO4.
Such an easy course of TNP substitution reactions with
various heteroatom nucleophiles stimulated us to study
reactivity of 1 toward NH‐azoles capable to ionize N H bond,
fully or partially, in water under the action of NaOH.
Figure 3 General view of the salt NH4-5a in representation of atoms via
thermal ellipsoids at 50% probability level.
We have found that TNP indeed reacts with various
nitropyrazoles, 2‐methyl‐4‐nitroimidazole, and 1,2,4‐triazole
conversion of TNP was observed after 10 h of reaction, and
this was visualized by the precipitation of red solid which
proved to be (alkyl)ammonium salt of 4‐NR′R″‐
dinitropyrazole from initially homogeneous solution [26].
The following treating of the intermediate salt with 20%
H2SO4 furnishes the final 4‐substituted 3,5‐dinitro‐1H‐
pyrazoles 5a–h (see Scheme 3).
The formation of 5a [4,27] was confirmed by the XRD
study of the semi hydrate of its ammonium salt NH4‐5a
(see Fig. 3). The additional prove came from the indepen-
dent synthesis of 5a via the alkaline hydrolysis of carba-
mate 7 [28] (Scheme 4).
in water in the presence of two equivalents of NaOH. All
these reactions also represent the nucleophilic substitution
of a nitro group at position 4 in TNP nucleus affording
the previously unknown 3,5‐dinitro‐4‐(N‐azolyl)pyrazoles
11a–f (Scheme 5).
Unlike the case of the discussed above reactions of TNP
with aliphatic amines and anionic O‐ and S‐nucleophiles,
the reactions with azoles require 9 hours of heating at
80–90°C for completion.
At the same conditions, the NH‐azoles having pKa less
than 9, such as 4‐nitro‐5(3)‐carboxamidopyrazole, 3(5),4‐
dinitropyrazole and 3‐nitro‐1,2,4‐triazole do not react with
TNP. Despite these results, the reaction of TNP with azoles
could be regarded as an efficient synthetic procedure,
complementary to the known synthetic approaches to the
In the same manner as with amines, in the presence of
inorganic bases, TNP reacts with phenols, triflouroethanol,
and thiols to form 4‐substituted 3,5‐dinitro‐1H‐pyrazoles
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
Scheme 4
feature has a pronounced effect on the reactivity toward the
nucleophiles—the unusual substitution occurs at the position
4 even in theanionic form of 1. Having this result in mind, it
was quite challenging to study the reactivity of MTNP in the
reactions with various S‐, N‐, and O‐nucleophiles.
We have found that with all aforementioned nucleophiles
MTNP behaves completely different compared to TNP: in
all the cases, the nucleophilic substitution of a nitro group
takes place regiospecifically at the position 5.
4‐(N‐azolyl)pyrazoles [30]. 4‐(N‐Azolyl)pyrazoles them-
selves represent an important class of compounds due to
their diverse biological activity [31] as well as due to
their potential as the polydentate ligands in Pd‐catalyzed
amination reactions [32].
The list of N‐nucleophiles chosen for the study of
MTNP reactivity includes ammonia, aliphatic primary and
secondary amines, aromatic and heteroaromatic amines,
hydrazide, and NH‐azoles (Scheme 6). The reactions were
carried out in methanol at room temperature using two
equivalents of the appropriate nucleophile. Under these
conditions, the products 12 were isolated in 60–90% yields,
and the full conversion of the starting compounds was
achieved after 2 h for the case of amines. For the completion
of the reactions with NH‐azoles, much longer time was
required, in some cases up to 48 h. This fact could be
explained by the very low basicity of the reagents (pKBH+
for alkylpyrazoles 3.04–2.48; for 2‐methyl‐4‐nitroimidazole,
0.86; for 1,2,4‐triazole, 2.45) [18]. The azole‐containing
products 13 are formed in 60–80% yields.
Therefore, the easy nucleophilic substitution of 4‐NO2‐
group in pyrazole family has been established for the first
time based on reactivity study of the wide range of
compounds. It was only known that the substitution in
1‐R‐3,4‐dinitropyrazoles with various nucleophiles occurs
exclusively at the position 3. The products of substitution
at position 4 have never been documented even in trace
amounts despite the activating nature of 3‐NO2 group
[3,5]. Another important noting is that the interaction of
nucleophiles with TNP is virtually the interaction with its
anion which is readily formed at the reaction conditions
(two equivalents of alkali). Thus, such an easy nucleophilic
substitution occurring in the anionic form of TNP looks
hardly possible at the first glance. Hence, the reactions
of TNP open new synthetic challenges in the pyrazole
chemistry through functionalization of position 4 via
nucleophilic substitution in TNP anion.
Nucleophilic substitution in MTNP. From the XRD data
on TNP 1, its salt 3c, and MTNP 4 (vide supra) it is clearly
seen that the main structural feature in all the molecules is
the pronounced tilting of 4‐NO2 group in respect to the
plane of the pyrazole core. This points out to the low degree
of conjugation (if any) between the aromatic heterocyclic
ring and this substituent. In the case of TNP itself, such a
The least basic nitropyrazoles used in our experiments
+
(pKBH for 4‐nitropyrazole, 2.0; for 3‐nitropyrazole, 4.66
[18]) did not react with MTNP without addition of a base
assisting the transformation of a reagent into its more
nucleophilic anionic form (pKa of nitropyrazoles ∼9.6–
9.8 [18]). Thus, the reactions of MTNP with nitropyrazoles
in the presence of one equivalent of NaOH in aqueous
acetonitrile accomplish in one hour affording the products
14a,b in 80–90% yield (Scheme 6).
The anionic forms of O‐ and S‐nucleophiles react with
MTNP much easier than that of N‐nucleophiles (Scheme 7).
Phenols, among them those containing one and two nitro
groups, as well as propargyl alcohol and oximes in the pres-
ence of 1 equiv of NaOH were used as O‐nucleophiles in
Scheme 5
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
Scheme 6
our experiments. The reactions were carried out in aqueous
acetonitrile at room temperature, under these conditions the
full conversions were achieved in 1 h, and the yields of
products 15, 16, and 17 were about 66–85%.
Being the most reactive among used by us, heteroatomic
anionic nucleophiles, S‐nucleophiles, react with MTNP at
room temperature very quickly—the reactions accomplish in
15 min giving the products 18 yields up to 95%. In the case
of ethanethiol, the reaction even needed the external cooling.
Therefore, compounds 12–18 are the products of
regioselective nucleophilic substitution of a nitro group at
position 5 of the pyrazole unit.
Then we have found that one of the remaining in 12
nitro groups, i.e., 3‐NO2, could also be substituted
(Scheme 8). Several example reactions have also shown
that dinitropyrazoles 12 react selectively with nucleophiles
to produce the products of 3‐NO2 substitution. These data
are in agreement with our previous results [5]. But such a
process needs much more drastic conditions—the reflux for
12 h with an excess of the amine in methanol. These reaction
sequence—double nucleophilic substitution of 5‐NO2
and then 3‐NO2—opens a synthetic route to unsymmetrical
core, i.e., C4 and C3,5. This tells us about symmetrical
structure of all products.
The additional proves of the products structures come
from the NMR study of compound 6 which is the product
of 5b N‐methylation (Scheme 2). Two dimensional correla-
tion spectroscopy NMR HMBC allows one to recognize
the long‐range spin‐coupling constant 1H–13C between
NHCH3 proton and carbon atoms C3 (δ 140.80 ppm) and
C5 (δ 133.82 ppm). These data together with chemical
shift of carbon atom adjacent to the NHCH3 fragment
(δ 130.87 ppm) and with the absence of the spin–spin
interactions between NHCH3 and N1 CH3 (NOESY data)
clearly show that the fragment NHCH3 in the product 5b
is located at position 4 of the pyrazole ring.
The structures of the all the products of MTNP substitu-
tion reactions 12–18 were established on the bases of their
13C‐NMR spectra as well as by the comparison of them to
13C‐NMR spectra of products 5, 8, 9, and 11. For the
detailed assignments of the signals, the same rules as for
spectra of 5, 8, 9, and 11 were applied.
The characteristic feature of 1H‐NMR spectra of
the products 12–18 is the position of N‐Me signal, δ
3.60–4.00, compared to isomeric 4‐substituted N‐methyl‐
3,5‐dinitropyrazoles where the signals have δ ≥ 4.15 ppm
(see lit. [8,13,32]). Moreover, the additional characteristic
parameter in the spectra of 12–18 is the existence of
high‐field signal C4–NO2 as well as two low‐field
signals assigned to C3 and C5, one of them (C3–NO2)
being broadened.
The additional prove of the structure 12b which is the
isomer of the product 6 was made using two‐dimensional
NMR techniques HMBC and NOESY. In HMBS spectrum,
the long‐range 1H–13C spin coupling for C5 (δ 147.50 ppm)
is observed not only for the group NHCH3 but also for the
protons of the fragment N1–CH3. Moreover, the NOESY
experiment shows the interaction of NHCH3 protons with
those of N1–CH3 group. This is possible only in the case
3,5‐diamino‐4‐nitropyrazoles 19.
NMR Studies of the synthesized compounds. The structures of
all the products of TNP substitution reactions (5a–h, 8a–f,
9a–f, 10, and 11a–f) were confirmed by 13C‐NMR spectroscopy
with the help of the reference signals of compound 5a
whose structure was unequivocally established by XRD
and by synthetic transformation of 7 (vide supra). For the
correct assignment of carbon signal, the rules well known
for nitropyrazoles has been applied—the consequence of
chemical shift is in the row C3≥C5>C4 [2,3]—together
with quadrupole broadening of the signal of carbons bound
to NO2 groups on 14N nuclei.
Because of the fast NH‐exchange process, in all 13C‐
NMR spectra of the products of TNP substitution reactions
are seen only two signals of carbon atoms of the pyrazole
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
Scheme 7
when NHCH3 group is positioned at the position 5 of the
pyrazole ring (Fig. 4).
activation energies by the difference in positive charges at
positions 3 and 5 [6].
The features of nucleophilic substitution reactions in TNP
and MTNP. The above‐described unusual reactivity of TNP
Without detailed structural data on molecules of TNP
and MTNP, the reasonable explanation of the difference
in their reactivity toward the same nucleophiles could be
the difference in the degree of conjugation of 4‐NO2 group
with the pyrazole nucleus. However, XRD data discussed
above unequivocally and data Herve [9] show that in
TNP, in its salts, and in MTNP, the plane of the 4‐NO2
group is tilted significantly, and the dihedral angles are
nearly the same for three different molecules. This means
that in all the cases, the conjugation between 4‐NO2 and
pyrazole ring is neglectable. At the same time, two other
nitro substituents (3‐NO2 and 5‐NO2) lie almost in the
plane of the central core.
All these data allow us to conclude that the reason for the
unusual substitution of 4‐NO2 group in TNP should be
related to the anionic form of TNP in those reactions. It
is commonly accepted that the nucleophilic substitution in
N‐anions of nitropyrazoles is not possible [7]. It is well‐
accepted knowledge, that the position 4 in pyrazoles is
considered as “electrophilic” and positions 3 and 5 as
“nucleophilic.” This governs the electrophilic nitration on
position 4, and nucleophilic substitution on positions 3
and 5 [1,6–8].
needs the explanation. The mild conditions of the reactions
—generally, room temperature, water—that are not typical
for the aromatic nucleophilic substitution also require the
comment. At the first glance, the reasonable explanation of
the substitution of 4‐NO2 group in TNP is the presence
of two adjacent electron‐withdrawing nitro groups at
positions 3 and 5 of the pyrazole ring which enhance the
reactivity of the internal NO2. If so, one should expect the
same 4‐NO2 substitution also in MTNP. However, our
experiments clearly show that in this case, the only leaving
group is the NO2 at position 5, and 4‐NO2 does not take
any part in the reaction.
This behavior of MTNP follows the course of reactions
found recently in our lab: in the case of N‐substituted 4‐Z‐
1‐R‐3,5‐dinitropyrazoles, the nucleophiles substitute only
5‐NO2 group independent on the nature of 4‐Z and 1‐R
substituents [6–8]. Such a result was confirmed by quantum
chemical calculations which explains the difference in
Scheme 8
Figure 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
Table 1
Crystal data and structure refinement parameters for 1, 3c, 4, and NH4‐5a.
1
3c
NH4‐5a
4
Empirical formula
Formula weight
T (K)
C3HN5O6
203.09
100
C5H5N9O6
287.18
100
C6H14N12O9
398.29
C4H3N5O6
217.11
100
100
Crystal system
Space group
Z
Monoclinic
P21/c
Orthorhombic
P2111
Triclinic
P‐1
Orthorhombic
Pna21
12
4
2
4
a (Å)
b (Å)
c (Å)
α (°)
15.0080 (5)
8.1732 (3)
17.1160 (5)
90.00
92.2510 (10)
90.00
5.11410 (10)
11.5978 (2)
17.5197 (3)
90.00
90.00
90.00
1039.13 (3)
1.836
7.71350 (10)
8.11350 (10)
13.6005 (2)
104.8350 (10)
95.5290 (10)
108.8760 (11)
763.461 (18)
1.733
11.7333 (3)
8.2594 (2)
8.3398 (2)
90.00
90.00
90.00
808.21 (3)
1.784
1.69
β (°)
γ (°)
V (Å3)
2097.89 (12)
1.929
Dcalc (g cm−3
)
Linear absorption, μ (cm−1
F(000)
)
1.88
1224
1.66
584
1.59
412
440
2θmax (°)
60
60
60
59
Reflections measured
Independent reflections
99,797
6120
46,209
1777
50,284
4444
37,641
1252
Observed reflections [with I > 2σ(I)]
5500
1728
4186
1249
Parameters
391
201
304
149
R1
wR2
0.0330
0.0957
1.007
0.0239
0.0665
1.001
0.0300
0.0940
1.008
0.465/−0.321
0.0219
0.0602
1.005
GOF
Δρmax/Δρmin (e Å−3
)
0.524/−0.335
0.360/−0.206
0.279/−0.178
on a Specord UV VIS instrument. Mass spectra were obtained
on a FINNIGAN MAT INCOS 50 and Bruker MicrOTOF II
instruments. Elemental analysis was performed with a Perkin‐Elmer
Series II 2400 analyzer. The course of the reactions was monitored
and the purity of the compounds was checked by TLC on Merck
Silicagel 60 F254 plates.
Our results show the inversion of reactivity of TNP
on going from neutral heterocycle to its anion: the
“electrophilic” position becomes “nucleophilic.”
CONCLUSIONS
X‐Ray diffraction experiments. XRD experiments for 1, 3c, 4,
and NH4‐5a were carried out with a Bruker’s SMART APEX2
CCD diffractometer [λ(MoKα) = 0.71072 Å, ω‐scans]. The
structures were solved by direct method and refined by the full‐
matrix least‐squares technique against F2 in the anisotropic–
isotropic approximation. Hydrogen atoms were located from the
Fourier synthesis of the electron density and refined in the
isotropic approximation. Crystal data and structure refinement
parameters for 1, 3c, 4, and NH4‐5a are summarized in Table 1.
All calculations were performed using SHELXTL PLUS 5.0. [33].
The calculated density of the compounds 1 and MTNP 4 at RT is
1.876 and 1.726 g cm−3, respectively. Note that despite the failure
to obtain the correct space group for 1 [23], the crystal densities
theoretically predicted for TNP 1 and MNTP 4 reproduce those
obtained from XRD data with ∼7% error.
This work shows that fully C‐nitrated pyrazole—TNP—
possesses the intriguing properties which distinguish it
from its congeners: its N‐anion undergoes the nucleophilic
substitution of 4‐nitro group under mild conditions while
its covalent derivative—MTNP—behaves in completely
different way; here, the same nucleophiles substitute only
5‐nitro group. The data obtained in this work clearly show
that TNP is a novel, multipurpose building block in the
pyrazole family. The future applications of this novel
tecton will open unprecedented perspectives in the design
of new polyfunctional pyrazoles.
EXPERIMENTAL
3,4,5‐Trinitro‐1H‐pyrazole (1). A solution of 2 [16] (18.6 g,
0.12 mol) in a mixture of H2SO4 (d = 1.824 g cm−3, 186 mL)
and HNO3 (d = 1.51 g cm−3, 75 mL) was kept at 90–100°C for
10 h. The resulting mixture was poured into ice‐water (1 L),
and extracted with ethyl acetate (2 × 300 mL). The organic
layer was separated, washed with water, and dried over MgSO4.
The solvent was then removed in vacuo, and the residue was
crystallized from toluene. Yield: 20.7 g (87%) 1; mp 186°C
(ref. 9; mp 187.8°C, ref. 10; mp 182–184°C).
Melting points were determined on
a Reichert Kofler
thermopan apparatus and were uncorrected. NMR spectra were
recorded in DMSO‐d6 solutions (unless otherwise is stated) at
298 K on a “Bruker AC‐300” [operating at 300.13 MHz (1H),
75.47 (13C)] and “Bruker DRX‐500” [operating at 500.13 MHz
(1H), 125.77 (13C)] spectrometer. Tetramethylsilane was used as
1
an internal standard for H and 13C, and CH3NO2 was used as
an internal standard for 14N, high‐field chemical shifts are given
with the minus sign. IR spectra were measured on a Bruker
ALPHA spectrometer in KBr pellets and UV spectra were recorded
Synthesis of 3,4,5‐trinitro‐1H‐pyrazole salts 3a‐c (general
procedure). To the solution of trinitropyrazole 1 (0.5 mol) in
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
MeOH (3 mL) was added ammonia (25% solution in water, 1
equiv) or KOAc (1 equiv) or N‐amino‐1,2,4‐triazole (1 equiv) in
MeOH (3 mL). The mixture was stirred for 4 h at room
temperature. The solvent was then removed in vacuo, the
residue was washed with ether and dried over P2O5 in cases 3a
and 3b. In the case of 3c, the precipitate formed was filtered off,
washed with ether, and dried over P2O5.
3,4,5‐Trinitro‐1H‐pyrazole ammonium salt (3a). Yield 89%;
mp 195–198°C; 13C‐NMR: δ 122.06 (C4), 146.90 (C3,5). Anal.
Calcd. for C3H4N6O6: C, 16.37; H, 1.83; N, 38.18. Found: C,
16.52; H, 1.90; N, 40.11.
3,4,5‐Trinitro‐1H‐pyrazole potassium salt (3b). Yield 95%;
mp 199–201°C; 13C‐NMR: δ 122.03 (C4), 147.24 (C3,5). Anal.
Calcd. for C3KN5O6: C, 14.94; K, 16.21; N, 29.04. Found: C,
15.14; K, 16.36; N, 29.63.
3,4,5‐Trinitro‐1H‐pyrazole N‐amino‐1,2,4‐triazolium solt (3c). Yield
90%, mp 165°C. 13C‐NMR: δ 122.06 (C4), 143.97, 146.91 (C3,5). Anal.
Calcd. for C5H5N9O6: C, 20.91; H, 1.76; N, 43.90. Found: C, 21.23; H,
1.88; N, 44.60.
Synthesis of 1‐methyl‐3,4,5‐trinitro‐1H‐pyrazole (4) and
1‐methyl‐4‐methylamino‐3,5‐dinitro‐1H‐pyrazole (6) (general
procedure). To the solution of NaHCO3 (0.51 g, 6 mmol) in
water (10 mL), compounds 1 or 5b (3 mmol) were added. The
mixture was stirred for 10 min, followed by addition of Me2SO4
(0.34 mL, 3.6 mmol). The stirring was continued for 4 h at room
temperature. The precipitate formed was filtered off and dried
over P2O5.
Calcd. for C4H5N5O4: C, 25.68; H, 2.69; N, 37.43. Found: C,
25.90; H, 2.81; N, 37.84.
3,5‐Dinitro‐4‐(pyrrolidin‐1‐yl)‐1H‐pyrazole (5c). Yield 80%;
mp 170–172°C; IR: 3330, 2944 (NH), 1612, 1420, 1366, 1304,
1
(NO2) cm−1; H‐NMR: δ 1.92 (m, 4H), 3.36 (m, 4H); 13C‐NMR:
δ 25.44, 51.92, 125.17 (C4), 141.39 (C3,5); ms: m/z 227 (M)+.
Anal. Calcd. for C7H9N5O4: C, 37.01; H, 3.99; N, 30.83. Found:
C, 37.19; H, 4.05; N, 31.16.
4‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl)morpholine (5d). Yield 74%;
T. decomp. 238°C; IR: 3024, 2972 (NH), 1604, 1500, 1456,
1392, 1368 (NO2) cm−1; 1H‐NMR: δ 3.22 (m, 4H), 3.75 (m, 4H);
13C‐NMR: δ 50.79, 66.43, 126.22 (C4), 143.50 (C3,5); ms: m/z
243 (M)+. Anal. Calcd. for C7H9N5O5: C, 34.57; H, 3.73; N,
28.80. Found: C, 34.74; H, 3.97; N, 29.02.
1‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl)azepane (5e). Yield 87%; mp
188–190°C; IR: 3022, 2980 (NH), 1600, 1556, 1480, 1392, 1336
1
(NO2) cm−1; H‐NMR: δ 1.65 (m, 8H), 3.24 (m, 4H); 13C‐NMR:
δ 27.60, 29.00, 53.74, 128.14 (C4), 144.15 (C3,5); ms: m/z 255
(M)+. Anal. Calcd. for C9H13N5O4: C, 42.35; H, 5.13; N, 27.44.
Found: C, 42.49; H, 5.21; N, 27.68.
1‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl)piperidine (5f). 89%; mp
166–168°C; IR: 3232, 2932, 2848 (NH), 1600, 1404, 1304
(NO2) cm−1; 1H‐NMR: δ 1.61 (m, 6H), 3.12 (m, 4H); 13C‐NMR:
δ 22.68, 25.94, 51.90, 127.60 (C4), 143.06 (C3,5); ms: m/z 241
(M)+. Anal. Calcd. for C8H11N5O4: C, 39.84; H, 4.60; N, 29.04.
Found: C, 40.06; H, 4.77; N, 29.40.
1‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl)‐4‐methylpiperidine (5g). Yield
74%; mp 138–139°C; IR: 3248, 2960, 2932 (NH), 1528, 1464,
4. Yield 92%; mp 90–91°C (CHCl3) (ref. 12; mp 91.3°C); IR:
1587, 1540, 1338 (NO2) cm−1
;
1H‐NMR ((CD3)2CO): δ 4.50
1364, 1300 (NO2) cm−1; H‐NMR: δ 0.93 (d, 3H), 1.30 (m, 2H),
1
(s, 3H); 13C‐NMR ((CD3)2CO): δ 43.86, 124.22 (C4), 139.70
(C5), 143.20 (C3); 14N‐NMR ((CD3)2CO): δ −31.23 (C3NO2),
−32.70 (C5NO2), −35.51 (C4NO2), −76.25 (N2), −182.79 (N1);
HRMS ESI(−): m/z 187.0119 Calc. for (M‐NO)−. 187.0109.
Anal. Calcd. for C4H3N5O6: C, 22.13; H, 1.39; N, 32.26.
Found: C, 22.28; H, 1.56; N, 32.57.
1.55 (m, 1H), 1.64 (m, 2H), 3.08 (m, 2H), 3.21 (m, 2H); 13C‐NMR:
δ 21.14, 28.02, 30.22, 34.02, 43.29, 51.25, 127.51 (C4), 146.86
(C3,5); ms: m/z 255 (M)+. Anal. Calcd. for C9H13N5O4: C, 42.35;
H, 5.13; N, 27.44. Found: C, 42.47; H, 5.28; N, 27.65.
1‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl)‐4‐methylpiperazine (5h). Yield
84%; T. decomp. 247°C; IR: 2960, 2692 (NH), 1596, 1412, 1402,
1372, 1304, 1272 (NO2) cm−1; 1H‐NMR: δ 2.81 (s, 3H), 3.15
(m, 2H), 3.42 (m, 4H), 3.58 (m, 2H); 13C‐NMR: δ 40.33, 47.35,
52.85, 125.08 (C4), 144.99 (C3,5); ms: m/z 256 (M)+. Anal. Calcd.
for C8H12N6O4: C, 37.50; H, 4.72; N, 32.80. Found: C, 37.67; H,
4.71; N, 32.93.
Preparation of 4‐amino‐3,5‐dinitro‐1H‐pyrazole 5a from carbamate
7. The solution of KOH (7.23g , 0.13 mol) and carbamate 7 [28]
(10 g, 0.043 mol) in H2O (100 mL) was heated at 80–90°C for 7
h. The resulting mixture was cooled down and left overnight. The
precipitate of potassium salt was filtered off, washed with ice‐
water, suspended in water, and acidified by 20% H2SO4 to pH 1.
The resulting precipitate was filtered off and dried over P2O5.
Yield 5 g (67%); mp 166–168°C (H2O) (ref. 27; mp 169–171°C).
Synthesis of 3,5‐dinitro‐4‐OR‐1H‐pyrazoles 8a–f and
3,5‐dinitro‐4‐SR‐1H‐pyrazoles 9a–f (general procedure). To
the solution of trinitropyrazole 1 (0.61 g, 3 mmol) in water
(10 mL), NaOH (0.24 g, 3 mmol) was added, and the mixture with
stirred for 10 min, then solution of NaOH (3 mmol) and the
appropriate phenol (or 2,2,2‐trifluoroethanole) (3 mmol) or thiol
(3.6 mmol) in water (10 mL) was added slowly. The stirring was
continued for 10 h in the case of phenols and 3 h in the case of
thiols at room temperature, then the mixture was acidified with 20%
H2SO4 to pH 1. The precipitate formed was filtered off, dried, and
crystallized from MeOH‐H2O. In the case of 8d, the resulting
mixture was extracted with ethyl acetate (2 × 10 mL). The organic
layer was separated and dried over MgSO4. The solvent was then
removed in vacuo, and the residue was washed with hexane.
6. Yield 90%; mp 130–131°C (CH2Cl2); IR: 3365, 3326, (NH);
1615; 1527, 1479, 1438, 1333, 1306 (NO2) cm−1; 1H‐NMR:
δ 2.95 (d, 3H, 3J = 5.3 Hz), 4.16 (s, 3H), 7.26 (br d, 1H, 3J = 4.9
Hz); 13C‐NMR: δ 33.10, 43.04, 130.87 (C4), 133.22 (C5), 140.80
(C3); ms: m/z 201 (M)+. Anal. Calcd. for C5H7N5O4: C, 29.86; H,
3.51; N, 34.82. Found: C, 30.25; H, 3.71; N, 35.44.
Synthesis of 4‐NR′R″‐3,5‐dinitro‐1H‐pyrazole 5a–h (general
procedure). To the solution of trinitropyrazole 1 (0.5 g, 2.5mmol)
in water (5 mL), the appropriate amine (10 equiv in the case of 5a,b
and 3.5 equiv in the case of 5c–h) was added and the reaction
mixture was left for 10 h at room temperature. The precipitate was
filtered off, washed with cold MeOH, suspended in 3 mL of water,
and acidified with 20% H2SO4 to pH 1. The resulting precipitate
was filtered off, dried, and crystallized from EtOH‐H2O (1:1).
4‐Amino‐3,5‐dinitro‐1H‐pyrazole (5a). Yield 80%; mp 166–168°C
(ref. 27; mp 169–171°C); uv: (H2O): λ max 260 nm (ε12,000), λ
max 400 nm (ε 9,600); (aq. NaOH): λ max 306 nm (ε 16,200), λ
max 400 nm (ε 8,400); (aq. H2SO4): λ max 222 nm (ε 12,400);
pKa = 3.42, pKBH+ = −5.43; IR: 3436, 3324, 3172 (NH); 1650,
1525, 1350 (NO2) cm−1; 13C‐NMR: δ 128.96 (C4), 138.84
(C3,5); 14N‐NMR ((CD3)2CO): δ −25.15 (ν1/2 80 Hz, NO2);
−
HRMS ESI(−): m/z 172.0117 (M‐H)−. Calc. for C3H2N5O4
172.0112.
4‐Methylamino‐3,5‐dinitro‐1H‐pyrazole (5b). Yield 87%; mp
170–171°C; IR: 3360, 3144 (NH), 1620, 1488, 1424, 1388, 1352,
1
1304 (NO2) cm−1; H‐NMR: δ 3.00 (c, 3H); 13C‐NMR: δ 33.31
(CH3), 129.83 (C4), 139.39 (C3,5); ms: m/z 187 (M)+. Anal.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
3,5‐Dinitro‐4‐phenoxy‐1H‐pyrazole (8a). Yield 50%; mp
162–164°C; IR: 3492, 3260 (NH), 1620, 1564, 1436, 1372, 1300
C9H5BrN4O4S: C, 31.32; H, 1.46; N, 16.23. Found: C, 31.58; H,
1.55; N, 16.36.
1
(NO2) cm−1; H‐NMR: δ 7.07 (m, 3H), 7.32 (m, 2H). 13C‐NMR:
4‐[(4‐Chlorophenyl)thio]‐3,5‐dinitro‐1H‐pyrazole (9d). Yield
85%; mp 138–139°C; IR: 3580, 3088 (NH), 1552, 1480, 1472,
δ 115.19 (CH), 123.26 (CH), 127.77 (C4), 129.79 (CH), 143.49
(C3,5), 156.73 (CO); ms: m/z 250 (M)+. Anal. Calcd. for
C9H9N4O5: C, 43.21; H, 2.42; N, 22.40. Found: C, 43.60; H,
2.59; N, 22.73.
1
1388, 1316 (NO2) cm−1; H‐NMR: δ 7.15 (d, 2H), 7.45 (d, 2H);
13C‐NMR: δ 103.88 (C4), 119.88, 129.90, 132.02, 133.81,
151.91 (C3,5). Anal. Calcd. for C9H5ClN4O4S: C, 35.94; H,
1.68; N, 18.63. Found: C, 36.41; H, 1.80; N, 18.83.
4‐(2‐Methoxyphenoxy)‐3,5‐dinitro‐1H‐pyrazole (8b). Yield
88%; mp 144–145°C; IR: 3490, 3488 (NH), 1556, 1512, 1372,
4‐[(4‐Chlorobenzyl)thio]‐3,5‐dinitro‐1H‐pyrazole (9e). Yield
95%; mp 166–167°C; IR: 2968, 2924 (NH), 1560, 1488, 1472,
1
1336 (NO2) cm−1; H‐NMR: δ 3.81 (s, 3H, Me), 6.80 (m, 1H),
6.88 (m, 1H), 7.03 (m, 1H), 7.13 (m, 1H). 13C‐NMR: δ 55.95,
113.29 (CH), 115.07 (CH), 120.60 (CH), 124.19 (CH), 128.68
(C4), 142.84 (C3,5), 145.76, 148.69 (C O); ms: m/z 280 (M)+.
Anal. Calcd. for C10H8N4O6: C, 42.87; H, 2.88; N, 20.00. Found:
C, 43.04; H, 2.95; N, 20.32.
1396, 1312 (NO2) cm−1; H‐NMR: δ 4.23 (s, 2H), 7.15 (d, 2H),
1
7.39 (d, 2H); 13C‐NMR: δ 38.19, 105.77 (C4), 128.40, 130.68,
131.15, 136.00, 152.32 (C3,5); ms: m/z 314, 316 (3:2) (M)+.
Anal. Calcd. for C10H7ClN4O4S: C, 38.16; H, 2.24; N, 17.80.
Found: C, 38.55; H, 2.30; N, 17.92.
4‐(4‐Chlorophenoxy)‐3,5‐dinitro‐1H‐pyrazole (8c). Yield 75%;
mp 129–131°C; IR: 3574, 2992 (NH), 1596, 1512, 1402, 1310
(NO2) cm−1; 1H‐NMR: δ 7.09 (d, 2H), 7.38 (d, 2H); 13C‐NMR: δ
117.20 (CH), 127.24, 127.46 (C4), 129.62 (CH), 143.47 (C3,5),
155.58 (C O); ms: m/z 284, 286 (2:3) (M)+. Anal. Calcd. for
C9H5ClN4O5 C, 37.98; H, 1.77; N, 19.69. Found: C, 38.33; H,
1.94; N, 19.78.
S‐(3,5‐Dinitro‐1H‐pyrazole‐4‐yl) hydrogen thiocarbonate
(9f). Yield 78%; mp 114–115°C; IR: 1712, 1680 (COOH),
1560, 1408, 1396, 1324, 1316 (NO2) cm−1 1H‐NMR: δ 3.72
;
(s, 2H); 13C‐NMR: δ 36.13, 106.30 (C4), 151.90 (C3,5),
170.34; ms: m/z 246 (M–2H)+. Anal. Calcd. for C5H4N4O6S: C,
24.20; H, 1.62; N, 22.58. Found: C, 24.42; H, 1.90; N, 22.77.
4‐Hydroxy‐3,5‐dinitro‐1H‐pyrazole disodium salt (10). To
the solution of NaHCO3 (1.05 g, 12.5 mmol) in water (5 mL),
trinitropyrazole 1 (0.5 g, 2.5 mmol) was added. The mixture
was heated at 80–90°C for 9 h. After cooling, EtOH (5 mL)
was added and the resulting mixture was kept at 0–5°C for 2 h.
The precipitate formed was filtered off, washed with EtOH, and
dried in vacuo over P2O5. Yield 0.15 g (28%); IR: 1556, 1488,
1348, 1320 (NO2) cm−1; 13C‐NMR: δ 145.08 (C4), 154.15 (C3,5);
HRMS ESI(–) C3N4O52− Na2+ m/z: 172.9956. Calc. for C3HN4O5−
[M − 2Na + H]− 172.9952. Anal. Calcd. for C3N4Na2O5: C, 16.53;
N, 25.70, Na, 21.09. Found: C, 16.70; N, 25.96, Na, 21.33.
Synthesis of 4‐(N‐azolyl)‐3,5‐dinitopyrazoles 11a–f (general
procedure). A solution of trinitropyrazole 1 (3 mmol), NH‐azole
(3 mmol), and NaOH (6 mmol) in water (10 mL) was stirred
at 80–90°C for 9 h. After cooling, the mixture was acidified
with 20% H2SO4 to reach pH 1. The precipitate formed was
filtered off, washed with cool water, and dried in vacuo over
P2O5. Recrystallization from EtOH‐H2O (1:1) gave analytically
pure samples.
4‐(3,4‐Dimethylphenoxy)‐3,5‐dinitro‐1H‐pyrazole (8d). Yield
67%; mp 206–208°C; IR: 3580, 2992 (NH), 1560, 1488, 1368,
1
1336 (NO2) cm−1; H‐NMR: δ 2.15 (s, 6H, Me), 6.76 (m, 1H),
6.83 (m, 1H), 7.03 (m, 1H); 13C‐NMR: δ 18.46 (Me), 19.39
(Me), 112.24 (CH), 116.13 (CH), 128.11 (C4), 130.37 (CH),
131.17, 138.00, 143.07 (C3,5), 154.81 (C O); ms: m/z 278 (M)+.
Anal. Calcd. for C11H10N4O5: C, 47.49; H, 3.62; N, 20.14.
Found: C, 47.85; H, 3.90; N, 20.41.
3,5‐Dinitro‐4‐[3‐(trifluoromethyl)phenoxy]‐1H‐pyrazole
(8e). Yield 50%; mp 136–138°C; IR: 3628, 3490, 2992 (NH), 1596,
1
1512, 1480, 1316 (NO2) cm−1; H‐NMR: δ 7.38 (m, 1H), 7.45
(m, 2H), 7.57 (m, 1H); 13C‐NMR: δ 112.44 (CH), 119.62 (CH),
120.20 (CH), 123.80 (q, CF3), 127.13 (C4), 131.30 (CH), 143.65
(C3,5), 157.05 (C O); ms: m/z 318 (M)+. Anal. Calcd. for
C10H5F3N4O5: C, 37.75; H, 1.58; N, 17.61. Found: C, 38.02; H,
1.66; N, 17.78.
3,5‐Dinitro‐4‐(2,2,2‐trifluoroethoxy)‐1H‐pyrazole (8f). Yield
49%; mp 133–135°C; IR: 3674, 3490, (NH), 1596, 1560,
1
1478, 1334 (NO2) cm−1; H‐NMR: δ 4.83 (q, 2H); 13C‐NMR: δ
3,5‐Dinitro‐4‐(4‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole (11a). Yield
61%; mp 215–216°C; IR: 3138 (NH), 1625, 1536, 1515,
70.18 (q, CH2), 121.32 (q, CF3), 131.44 (C4), 142.85 (C3,5),
161.06 (C–O); ms: m/z 256 (M)+. Anal. Calcd. for
C5H3F3N4O5: C, 23.45; H, 1.18; N, 21.88. Found: C, 23.62; H,
1.30; N, 22.17.
1
1417, 1325 (NO2) cm−1; H‐NMR: δ 8.45 (s, 1H), 9.24 (s, 1H);
13C‐NMR: δ 110.66 (C4), 133.77 (CH), 135.92 (C4′NO2), 136.69
(CH), 149.52 (C3,5); HRMS ESI(−): m/z 268.0064 (M–H)−. Calc.
for C6H2N7O6− 268.0072.
4‐(Ethylthio)‐3,5‐dinitro‐1H‐pyrazole (9a). Yield 70%; mp
92–93°C; IR: 3544, 3428 (NH), 1556, 1512, 1480, 1400,
3,5‐Dinitro‐4‐(3‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole
(11b). Yield 52%; T. decomp. 290°C; IR: 3162, 3139 (NH),
1557, 1389, 1342 (NO2) cm−1; 1H‐NMR: δ 7.23 (s, 1H), 8.31
(s, 1H); 13C‐NMR: δ 103.78 (CH), 110.78 (C4), 137.64 (CH),
149.45 (C3,5), 156.55 (C3′NO2); 14N‐NMR ((CD3)2CO): δ
−76.27 (br N2), −24.72, −21.62, (NO2); HRMS ESI(−): m/z
268.0060 (M‐H)−. Calc. for C6H2N7O6− 268.0072.
3,5‐Dinitro‐4‐(4‐methyl‐3‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole
(11c). Yield 63%; mp 150–151°C; IR: 3578, 3333 (NH), 1629,
1551, 1528, 1351, 1333 (NO2) cm−1; 1H‐NMR: δ 2.31 (s, 3H,
Me), 8.12 (s, 1H). 13C‐NMR: δ 9.39 (Me), 110.94 (C4), 114.28
(C4′), 136.31 (CH), 148.95 (C3,5), 154.56 (C3′NO2; HRMS ESI
(−): m/z 282.0207 (M ‐ H)−. Calc. for C7H4N7O6− 282.0218.
3,5‐Dinitro‐4‐(4‐chloro‐3‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole
(11d). Yield 80%; mp 135–136°C; IR: 3573, 3422 (NH), 1562,
1545, 1507, 1337 (NO2), 837 (CCl) cm−1; 1H‐NMR: δ 8.73
1
1348, 1320 (NO2) cm−1; H‐NMR: δ 1.15 (t, 3H), 2.95 (q, 2H);
13C‐NMR: δ 14.45, 28.85, 107.54 (C4), 151.62 (C3,5); ms: m/z
218 (M)+. Anal. Calcd. for C5H6N4O4S: C, 27.52; H, 2.75; N,
25.68. Found: C, 27.97; H, 2.92; N, 26.04.
3,5‐Dinitro‐4‐(phenylthio)‐1H‐pyrazole (9b). Yield 98%; mp
155–156°C; IR: 3540, 3428 (NH), 1556, 1512, 1440, 1376, 1320
(NO2) cm−1; 1H‐NMR: δ 7.35 (m, 5H); 13C‐NMR: δ 105.13 (C4),
127.05, 128.15, 129.33, 133.82, 151.58 (C3,5); ms: m/z 266 (M)+.
Anal. Calcd. for C9H6N4O4S: C, 40.60; H, 2.26; N, 21.05. Found:
C, 40.84; H, 2.38; N, 21.22.
4‐[(4‐Bromophenyl)thio]‐3,5‐dinitro‐1H‐pyrazole (9c). Yield
91%; mp 136–137°C; IR: 3588, 3088 (NH), 1552, 1472, 1404,
1
1388, 1316 (NO2) cm−1; H‐NMR: δ 7.17 (d, 2H), 7.45 (d, 2H);
13C‐NMR: δ 103.81 (C4), 119.80, 129.83, 132.02, 133.92,
152.10 (C3,5); ms: m/z 344, 346 (1:1) (M)+. Anal. Calcd. for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
(s, 1H); 13C‐NMR: δ 105.97 (C4′Cl), 110.21 (C4), 135.57 (CH),
149.31 (C3,5), 151.11 (C3′NO2); HRMS ESI(−): m/z 301.9678,
CH2); 13C‐NMR: δ 14.44, 37.62 (NMe), 43.70, 50.04, 60.93,
118.26 (C4), 146.64 (C5), 146.78 (C3), 154.57 (CO); ms: m/z 328
(M)+. Anal. Calcd. for C11H16N6O6: C, 40.25; H, 4.91; N, 25.60.
Found: C, 40.66; H, 5.05; N, 25.72.
−
303.9648 (3 :1) (M‐H)−. Calc. for C6HClN7O7 301.9671,
303.9643.
4‐(2‐Methyl‐4‐nitro‐1H‐imidazol‐1‐yl)‐3,5‐dinitro‐1H‐pyrazole
(11e). Yield 71%; mp 230–232°C; IR: 3162 (NH), 1627, 1506,
1379 (NO2), 1102 cm−1; 1H‐NMR: δ 2.35 (s, 3H, Me), 8.20
(s, 1H); 13C‐NMR: δ 13.68 (Me), 118.97 (CH), 123.75 (C4), 144.73
(C2′Me), 146.70 (C3,5), C4′NO2 signals were not observer; HRMS
ESI(−):m/z 268.0227 (M‐H)−. Calc. for C7H4N7O6− 268.0218.
3,5‐Dinitro‐4‐(1H‐1,2,4‐triazol‐1yl)‐1H‐pyrazole (11f). Yield
89%; mp 245–247°C; IR: 3456, 3138 (NH); 1624, 1533, 1448,
5‐(4‐Fluorophenylamino)‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole
(12g). Yield 71%; mp 160–162°C; IR: 3335 (NH), 1595, 1510,
1
1491, 1371 (NO2) cm−1; H‐NMR: δ 3.59 (s, 3H, NMe), 7.15
(m, 4H), 9.50 (br, 1H, NH); 13C‐NMR: δ 38.07 (NMe), 115.05
(C4), 115.64 (CH), 121.12 (CH), 136.22, 141.95 (C5), 147.17
(C3), 158.35 (d, CF, J = 240 Hz); ms: m/z 281 (M)+. Anal.
Calcd. for C10H8FN5O4: C, 42.71; H, 2.87; N, 24.91. Found: C,
42.96; H, 3.04; N, 25.37.
5‐(4‐Chlorophenylamino)‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole
(12h). Yield 90%; mp 110–111°C; IR: 3342, 3325 (NH), 1601,
1579, 1492, 1242 (NO2), 814 (Cl) cm−1; 1H‐NMR: δ 3.67 (s, 3H,
NMe), 7.02 (m, 2H), 7.32 (m, 2H), 9.60 (br, 1H, NH); 13C‐NMR:
δ 37.87 (NMe), 119.72 (C4, CH), 126.40, 128.92 (CH), 139.31,
141.01 (C5), 147.12 (C3); ms: m/z 297, 299 (1:1) (M)+. Anal.
Calcd. for C10H8ClN5O4: C, 40.35; H, 2.71; N, 23.53. Found: C,
40.49; H, 2.84; N, 23.87.
1
1333 (NO2) cm−1; H‐NMR: δ 8.20 (s, 1H), 8.82 (s, 1H); 13C‐
NMR: δ 142.71 (C4), 144.57 (CH), 148.62 (C3,5), 151.86 (CH);
14N‐NMR ((CD3)2CO): δ −140.73 (br N1), −71.21 (br N2),
−29.80, −24.55 (NO2); HRMS ESI(−): m/z 226.0325 (M–H)−.
Calc. for C5H2N7O−4 226.0319.
Synthesis of 1‐methyl‐3,4‐dinitro‐5‐NR′R″‐1H‐pyrazoles
12 and 13 (general procedure). To the solution of pyrazole 4
(2.0 mmol) in MeOH (10 mL), the 4 mmol of appropriate
amine (or 10 mmol NH3 and MeNH2 in the case of 12a,b as 24
and 40% solutions in water, respectively) was added, and the
reaction mixture was left for 2 h in the case of amines and 48 h
in the case of azoles at room temperature. The resulting mixture
was kept at 0–5°C, the precipitate formed was filtered off, dried
in vacuo over P2O5 and crystallized from MeOH‐H2O.
1‐Methyl‐3,4‐dinitro‐5‐(3‐nitrophenylamino)‐1H‐pyrazole
(12i). Yield 75%; mp 173–174°C; IR: 1577, 1524, 1497, 1350
1
(NO2) cm−1; H‐NMR: δ 3.72 (s, 3H, NMe), 7.34 (m, 1H), 7.56
(m, 1H), 7.85 (m, 2H), 10.0 (br, 1H, NH); 13C‐NMR: δ 37.76
(NMe), 111.60 (CH), 116.58 (CH), 117.12 (C4), 123.31 (CH),
130.40 (CH), 140.10 (C5), 142.12, 147.20 (C3), 148.41; ms: m/z
308 (M)+. Anal. Calcd. for C10H8N6O6: C, 38.97; H, 2.62; N,
27.27. Found: C, 39.36; H, 2.70; N, 27.62.
5‐Amino‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (12a). Yield 70%;
mp 122–123°C; IR: 3431, 3354, 3331 (NH), 1648; 1515, 1363
1
(NO2) cm−1; H‐NMR: δ 3.65 (s, 3H, NMe), 7.87 (br, 2H, NH2);
3‐[(1‐Methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)amino]‐1‐propyl‐1H‐
pyrazole (12j). Yield 60%; mp 120–121°C; IR: 3218, 2969 (NH),
1592, 1527, 1487, 1439, 1366 (NO2) cm−1; 1H‐NMR: δ 0.80
(t, 3H, Me), 1.72 (m, 2H, CH2), 3.62 (s, 3H, NMe), 3.93 (q, 2H,
CH2), 6.00 (m, 1H), 7.65 (m, 1H), 9.65 (br, 1H, NH); 13C‐NMR:
δ 10.69, 22.23, 38.15 (NMe), 52.84, 95.57 (CH), 113.82 (C4),
131.65 (CH), 141.98, 146.62 (C5, C3); ms: m/z 295 (M)+. Anal.
Calcd. for C10H13N7O4: C, 40.68; H, 4.44; N, 33.21. Found: C,
40.98; H, 4.60; N, 33.66.
1‐Ethyl‐N′‐(1‐methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)‐1H‐pyrazole‐
4‐carbohydrazide (12k). Yield 90%; mp 225–226°C; IR: 3226, 2985
(NH), 1666 (CO), 1593, 1552, 1506, 1462, 1343, 1220 (NO2) cm−1;
1H‐NMR: δ 1.36 (t, 3H, Me), 3.76 (s, 3H, NMe), 4.21 (q, 2H, CH2),
7.93 (s, 1H), 8.29 (s, 1H), 9.32 (br, 1H, NH), 10.64 (br, 1H, NH); 13C‐
NMR: δ 15.22, 39.11 (NMe), 46.75, 111.68 (C4), 114.34, 131.47
(CH), 138.66 (CH), 146.77 (C5, C3), 162.42 (CO); ms: m/z 324
(M)+. Anal. Calcd. for C10H12N8O5: C, 37.04; H, 3.73; N, 34.56.
Found: C, 37.30; H, 3.88; N, 35.02.
13C‐NMR: δ 35.81 (NMe), 108.25 (C4), 146.95 (2C, C3, C5);
ms: m/z 187 (M)+. Anal. Calcd. for C4H5N5O4: C, 25.68; H, 2.69;
N, 37.43. Found: C, 25.95; H, 2.84; N, 37.80.
1‐Methyl‐5‐methylamino‐3,4‐dinitro‐1H‐pyrazole (12b). Yield
84%; mp 165–166°C; IR: 3350 (NH), 1629, 1542, 1454, 1331
1
(NO2) cm−1; H‐NMR: δ 3.15 (d, 3H, J = 5.4 Hz, NHCH3), 3.85
(s, 3H, NMe), 7.65 (br q, 1H, J = 5.2 Hz, NHMe); 13C‐NMR: δ
31.05 (NHMe), 39.33 (NMe), 110.05 (C4), 147.50 (2C, C3, C5);
ms: m/z 201 (M)+. Anal. Calcd. for C5H7N5O4: C, 29.86; H, 3.51;
N, 34.82. Found: C, 30.06; H, 3.68; N, 35.15.
1‐Methyl‐3,4‐dinitro‐5‐(pyrrolidin‐1‐yl)‐1H‐pyrazole (12c). Yield
60%; mp 64–65°C; IR: 1586, 1547, 1451, 1396, 1323 (NO2) cm−1;
1H‐NMR: δ 1.96 (m, 4H), 3.50 (m, 4H), 3.86 (s, 3H, NMe); 13C‐
NMR: δ 25.39, 39.49 (NMe), 50.48, 115.07 (C4), 145.28 (C5),
146.96 (C3); ms: m/z 241 (M)+. Anal. Calcd. for C8H11N5O4: C,
39.84; H, 4.60; N, 29.04. Found: C, 40.12; H, 4.68; N, 29.38.
4‐(1‐Methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)morpholine (12d). Yield
64%; mp 92–93°C; IR: 1593, 1550, 1500, 1340 (NO2), 1110 cm−1;
1H‐NMR: δ 3.32 (m, 4H), 3.73 (m, 4H), 3.82 (s, 3H, NMe); 13C‐
NMR: δ 37.61 (NMe), 49.27, 66.31, 118.18 (C4), 146.49 (C5),
146.77 (C3); ms: m/z 257 (M)+. Anal. Calcd. for C8H11N5O5: C,
37.36; H, 4.31; N, 27.23. Found: C, 37.65; H, 4.46; N, 27.54.
1‐(1‐Methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)azepane (12e). Yield
61%; mp 65–66°C; IR: 1569, 1546, 1490, 1332 (NO2) cm−1;
1H‐NMR: δ 1.72 (m, 8H), 3.33 (m, 4H), 3.82 (s, 3H, NMe); 13C‐
NMR: δ 27.18, 29.27, 37.15 (NMe), 52.61, 118.44 (C4), 146.62
(C3), 148.72 (C5); ms: m/z 269 (M)+. Anal. Calcd. for
C10H15N5O4: C, 44.61; H, 5.62; N, 26.01. Found: C, 44.93; H,
5.84; N, 26.30.
1‐Methyl‐3,4‐dinitro‐5‐(1H‐pyrazol‐1‐yl)‐1H‐pyrazole (13a). Yield
76%; mp 104–105°C; IR: 1602, 1554, 1521, 1505, 1380, 1346 (NO2)
1
cm−1; H‐NMR: δ 3.88 (s, 3H, NMe), 6.71 (m, 1H), 8.05 (m, 1H),
8.34 (m, 1H); 13C‐NMR: δ 38.61 (NMe), 108.79 (CH), 119.98 (C4),
134.65 (CH), 136.14 (C5), 144.24 (CH), 145.91 (C3); ms: m/z 238
(M)+. Anal. Calcd. for C7H6N6O4: C, 35.30; H, 2.54; N, 35.29.
Found: C, 35.47; H, 2.63; N, 35.82.
5‐(Imidazol‐1‐yl)‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (13b). Yield
60%; mp 125–126°C; IR: 1556, 1488, 1368, 1316 (NO2) cm−1; 1H‐
NMR: δ 3.80 (s, 3H, NMe), 7.23 (m, 1H), 7.63 (m, 1H), 8.15
(m, 1H); 13C‐NMR: δ 36.99 (NMe), 120.12 (C4), 120.91 (CH),
129.92 (CH), 134.68 (C5), 138.68 (CH), 146.36 (C3); ms: m/z 238
(M)+. Anal. Calcd. for C7H6N6O4: C, 35.30; H, 2.54; N, 35.29.
Found: C, 35.65; H, 2.70; N, 35.72.
Ethyl 4‐(1‐methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)‐piperazine‐1‐
carboxylate (12f). Yield 82%; mp 123–124°C; IR: 1691 (COOR),
1582, 1498, 1432, 1251 (NO2) cm−1; 1H‐NMR: δ 1.20 (t, 3H,
Me), 3.25 (m, 4H), 3.50 (m, 4H), 3.82 (s, 3H, NMe), 4.10 (q, 2H,
1‐Methyl‐3,4‐dinitro‐5‐(1,2,4‐triazol‐1‐yl)‐1H‐pyrazole
(13c). Yield 63%; mp 110–111°C; IR: 1595, 1539, 1510, 1351,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
1279 (NO2) cm−1; 1H‐NMR: δ 3.91 (s, 3H, NMe), 8.62 (s, 1H), 9.23
(s, 1H); 13C‐NMR: δ 38.76 (NMe), 120.51 (C4), 133.30 (C5),
146.21 (C3), 148.44 (CH), 154.13 (CH); ms: m/z 239 (M)+. Anal.
Calcd. for C6H5N7O4: C, 30.13; H, 2.11; N, 41.00. Found: C,
30.28; H, 2.34; N, 41.56.
7.62 (m, 1H), 7.76 (m, 1H), 8.21 (m, 1H); 13C‐NMR: δ 36.49
(NMe), 114.86 (C4), 117.88 (CH), 126.12 (2 CH), 135.41 (CH),
139.04, 144.46 (C5), 145.91 (C3), 146.98. Anal. Calcd. for
C10H7N5O7: C, 38.85; H, 2.28; N, 22.65. Found: C, 39.28; H,
2.45; N, 22.86.
Synthesis of 1‐methyl‐3,4‐dinitro‐5‐(nitropyrazolyl)‐1H‐
pyrazoles 14 (general procedure). To the solution of NaOH
(2 mmol) in water (3 mL), the appropriate nitropyrazole (2 mmol)
was added, and the mixture with stirred for 10 min, then the
solution of pyrazole 4 (2 mmol) in CH3CN (10 mL) was added,
and the reaction mixture was left for 1 h at ambient temperature.
The solvent was then removed in vacuo, and the residue was
extracted with CHCl3 (3 × 5 mL). The organic layers were
combined and dried over MgSO4. The solvent was then removed
in vacuo, and the residue was crystallized from petroleum‐ether
(14a) or chromatographed on silica (eluent CHCl3, Rf 0.35) (14b).
1‐Methyl‐3,4‐dinitro‐5‐(3‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole
(14a). Yield 92%; oil; IR: 1556, 1512, 1472, 1348, 1320 (NO2)
cm−1; 1H‐NMR: δ 3.95 (s, 3H, NMe), 7.50 (m, 1H), 8.15
(m, 1H); 13C‐NMR: δ 38.64 (NMe), 104.86 (CH), 120.98 (C4),
134.40 (C5), 139.26 (CH), 146.05 (C3), 158.67 (C3′NO2); ms:
m/z 283 (M)+. Anal. Calcd. for C7H5N7O6: C, 29.69; H, 1.78; N,
34.63. Found: C, 30.05; H, 2.02; N, 34.92.
1‐Methyl‐3,4‐dinitro‐5‐(3,5‐dinitrophenoxy)‐1H‐pyrazole (15d).
Yield 85%; mp 205–206°C; IR: 1625; 1552, 1519, 1368, 1350
1
(NO2), 1248 cm−1; H‐NMR: δ 3.90 (s, 3H, NMe), 8.67 (s, 2H),
8.71 (s, 1H); 13C‐NMR: δ 36.68 (NMe), 115.25 (C4), 115.31 (CH),
117.83 (2 CH), 144.05 (C5), 146.03 (C3), 148.97, 155.10; HRMS
ESI(+): m/z 377.0088 (M + Na)+, calc. for C10H6N6O9 + Na+
377.0088; m/z 372.0539 (M + NH4)+, calc. for C10H6N6O9 + NH+4
372.0535.
5,5′‐[1,4‐Phenylenebis(oxy)]bis(1‐methyl‐3,4‐dinitro‐1H‐
pyrazole) (15e). Yield 84%; mp 230–232°C; IR: 1566, 1515, 1493,
1366, 1335 (NO2), 1227, 1164 cm−1; 1H‐NMR: δ 3.83 (s, 6H,
NMe), 7.49 (s, 4H); 13C‐NMR: δ 36.41 (NMe), 114.95 (C4),
117.51 (4 CH), 145.53 (C5), 145.86 (C3), 151.87 (CO); HRMS
ESI(+): m/z 473.0408 (M + Na)+, calc. for C14H10N8O10 + Na+
473.0412; m/z 468.0849 (M + NH4)+, calc. for C14H10N8O10
+
NH+4 468.0858.
Acetone O‐(1‐methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)oxime (16a).
Yield 82%; mp 90–92°C; IR: 1588, 1536, 1432, 1336 (NO2) cm−1;
1H‐NMR: δ 1.96 (s, 3H, CMe), 2.17 (s, 3H, CMe), 3.84 (s, 3H,
NMe); 13C‐NMR (CDCl3): δ 16.79, 20.95, 36.91 (NMe), 115.63
(C4), 145.80 (C5), 148.96 (C3), 165.57; ms: m/z 243 (M)+. Anal.
Calcd. for C7H9N5O5: C, 34.57; H, 3.73; N, 28.80. Found: C,
34.76; H, 3.81; N, 29.24.
1‐Methyl‐3,4‐dinitro‐5‐(4‐nitro‐1H‐pyrazol‐1‐yl)‐1H‐pyrazole
(14b). Yield 71%; mp 108–109°C; IR: 1602, 1590, 1549, 1525,
1
1406, 1365, 1311 (NO2) cm−1; H‐NMR: δ 3.97 (s, 3H, NMe),
8.86 (s, 1H), 9.52 (s, 1H); 13C‐NMR: δ 38.67 (NMe), 120.09
(C4), 134.27 (C5), 135.36 (CH), 137.34 (C4′NO2), 139.35 (CH),
146.04 (C3); ms: m/z 283 (M)+. Anal. Calcd. for C7H5N7O6: C,
29.69; H, 1.78; N, 34.63. Found: C, 30.12; H, 1.93; N, 35.06.
Syntheses of 1‐methyl‐3,4‐dinitro‐5‐OR‐1H‐pyrazoles 15a–e,
16a,b, 17 and 1‐methyl‐3,4‐dinitro‐5‐SR‐1H‐pyrazoles 18a–d
(general procedure). To the solution of NaOH (2 mmol) in water
(3 mL), the appropriate phenol, oxime, propargyl alcohol, or thiol
(2 mmol) was added, and the mixture was stirred for 10 min, then
solution of pyrazole 4 (2 mmol) in CH3CN (10 mL) was added
(in the case of 15e: 4 mmol NaOH and 4 mmol of pyrazoles 4),
and reaction mixture was left for 1 h in the case of phenols and
oximes or for 15 min in the case of thiols at ambient temperature.
The solvent was then removed in vacuo, and the residue
was filtered off and washed with water. In the case of 15d,e, the
precipitates formed were filtered off. All compounds were
crystallized from MeOH‐H2O.
1‐Phenylethanone O‐(1‐methyl‐3,4‐dinitro‐1H‐pyrazol‐5‐yl)
oxime (16b). Yield 86%; mp 135–136°C (decomp.); IR: 1591,
1541, 1432, 1337 (NO2) cm−1 1H‐NMR (CDCl3): δ 2.61
;
(s, 3H, CMe), 3.96 (s, 3H, NMe), 7.50 (m, 3H), 7.63 (m, 2H);
13C‐NMR (CDCl3): δ 14.45, 37.09 (NMe), 113.65 (C4), 126.94
(CH), 129.06 (CH), 131.49 (CH), 132.97 (CH), 138.65 (C5),
148.85 (C3), 164.87; ms: m/z 305 (M)+. Anal. Calcd. for
C12H11N5O5: C, 47.22; H, 3.63; N, 22.94. Found: C, 47.36; H,
3.77; N, 23.52.
1‐Methyl‐3,4‐dinitro‐5‐(prop‐2‐yn‐1‐yloxy)‐1H‐pyrazole (17).
Yield 66%; mp 75–76°C; IR: 3286, 3271 (HC=), 1558, 1512,
1377, 1338 (NO2) cm−1; 1H‐NMR: δ 3.71 (s, 3H, NMe), 3.95 (s,
1H), 5.23 (s, 2H); 13C‐NMR (CDCl3): δ 36.31 (NMe), 64.21
(CH2), 75.61 (–C=), 79.98 (HC=), 115.60 (C4), 146.82 (C3),
148.05 (C5); ms: m/z 226 (M)+. Anal. Calcd. for C7H6N4O6: C,
37.18; H, 2.67; N, 24.77. Found: C, 37.34; H, 2.88; N, 25.03.
5‐Ethylthio‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (18a). Yield 80%;
mp 68–70°C; IR: 1556, 1472, 1348, 1326 (NO2) cm−1; 1H‐NMR: δ
1.22 (t, 3H, Me), 3.08 (q, 2H, CH2), 4.05 (s, 3H, NMe); 13C‐NMR
(CDCl3): δ 15.19, 30.15, 38.89 (NMe), 129.85 (C4), 136.96 (C5),
146.14 (C3); ms: m/z 232 (M)+. Anal. Calcd. for C6H8N4O4S: C,
31.03; H, 3.47; N, 24.13. Found: C, 31.15; H, 3.68; N, 24.30.
1‐Methyl‐3,4‐dinitro‐5‐phenylthio‐1H‐pyrazole (18b). Yield
72%; mp 100–101°C; IR: 1546, 1527, 1488, 1355, 1327 (NO2)
cm−1; 1H‐NMR: δ 3.95 (s, 3H, NMe), 7.42 (m, 5H, Ph); 13C‐NMR:
δ 39.19 (NMe), 128.49 (CH, C4), 129.65 (CH), 130.21, 130.31
(C5), 146.72 (C3); ms: m/z 280 (M)+. Anal. Calcd. for
C10H8N4O4S: C, 42.86; H, 2.88; N, 19.99. Found: C, 43.15; H,
3.01; N, 20.37.
5‐(4‐Bromophenoxy)‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (15a).
Yield 82%; mp 118–120°C; IR: 1557, 1514, 1482, 1367, 1234
1
(NO2) cm−1; H‐NMR: δ 3.82 (s, 3H, NMe), 7.31 (d, 2H), 7.63
(d, 2H); 13C‐NMR: δ 36.35 (NMe), 115.08 (C4), 117.15 (CBr),
117.89 (CH), 132.58 (CH), 145.15 (C5), 145.83 (C3), 154.26
(CO); ms: m/z 342, 344 (1:1) (M)+. Anal. Calcd. for
C10H7BrN4O5: C, 35.01; H, 2.06; N, 16.33. Found: C, 35.25; H,
2.18; N, 16.52.
5‐(3‐Methoxyphenoxy)‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (15b).
Yield 80%; mp 91–92°C; IR: 1616; 1560, 1520, 1492, 1434, 1338,
1227 (NO2), 1129 cm−1; 1H‐NMR: δ 3.73 (s, 3H, NMe), 3.81
(s, 3H, OMe), 6.84 (m, 3H), 7.37 (m, 1H); 13C‐NMR: δ 36.30
(NMe), 54.76 (OMe), 102.32 (CH), 107.66 (CH), 110.84 (CH),
115.19 (C4), 130.80 (CH), 145.37 (C5), 145.75 (C3), 155.89,
160.81. Anal. Calcd. for C11H10N4O6: C, 44.90; H, 3.43; N, 19.04.
Found: C, 45.25; H, 3.60; N, 19.18.
1‐Methyl‐5‐(4‐methylphenyl)thio‐3,4‐dinitro‐1H‐pyrazole (18c).
Yield 95%; mp 103–104°C; IR: 1549, 1518, 1491, 1355, 1326 (NO2)
cm−1; 1H‐NMR: δ 2.26 (s, 3H, Me), 3.90 (s, 3H, NMe), 7.21 (m, 2H),
7.36 (m, 2H); 13C‐NMR: δ 20.72, 38.94 (NMe), 129.98 (2C CH, C4),
134.24, 135.91, 137.91 (C5), 146.17 (C3); ms: m/z 294 (M)+. Anal.
1‐Methyl‐3,4‐dinitro‐5‐(2‐nitrophenoxy)‐1H‐pyrazole (15c).
Yield 70%; mp 151–152°C; IR: 1611; 1595, 1558, 1517, 1376,
1
1347 (NO2) cm−1; H‐NMR: δ 3.95 (s, 3H, NMe), 7.51 (m, 1H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis and Comparison of the Reactivity of 3,4,5‐1H‐Trinitropyrazole and Its
N‐Methyl Derivative
[11] Zhang, Y.; Guo, Y.; Joo, Y. ‐H.; Parrish, D. A.; Shreeve, J. M.
Chem Eur J 2010, 16, 10778.
Calcd. for C11H10N4O4S: C, 44.89; H, 3.43; N, 19.04. Found: C,
45.11; H, 3.68; N, 19.40.
[12] (a) Nielsen, A. T.; Norris, W. P.; Atkins, R. L.; Vuono, W. R. J
Org Chem 1983, 48, 1056; (b) Agraval, J. P.; Hodgson, R. D. Organic
Chemistry of Explosives; Wiley: Chichester, 2007; (c) Manelis, G. B.;
Nazin, G. M.; Rubtsov, Yu, I.; Strunin, V. A. Termal Decompozition
and Combustion of explosives and Propellants; Taylor Francis: London,
2003; (d) F. Benedetti, D. Marshall, Ch Stirling, Y. Lend, J. Chem Soc
Chem Commun 1982, 918; (e) Serushkina, O. V.; Dutov, M. D.; Solkan,
V. N.; Shevelev, S. A. Russ Chem Bull (Engl Transl), 2001, 50, 2406; (f)
Shevelev, S. A.; Dalinger, I. L.; Cherkasova, T. I. Tetrahedron Lett 2001,
42, 8539; (d) Rozhkov, V. V.; Kuvshinov, A. M.; Gulevskaya, V. I.;
Chervin, I. I.; Shevelev, S. A. Synthesis 1999, 2065.
[13] The preliminary communication see: Dalinger, I. L.; Vatsadze,
I. A.; Popova, G. P.; Shkineva, T. K.; Shevelev, S. A. Mendeleev
Commun 2010, 20, 253.
[14] The preliminary communication see: Dalinger, I. L.; Vatsadze,
I. A.; Popova, G. P.; Shkineva, T. K.; Shevelev, S. A. Mendeleev
Commun 2010, 20, 355.
[15] In contrast to our data, Herve et al. [9] claimed that the nitric‐
sulfuric acids mixture is not applicable for the nitration of 2, and this
reaction could occur only upon addition to the nitration mixture a great
excess of 60% oleum.
[16] Janssen, J. W. A. M.; Koeners, H. J.; Kruse, C. G.; Habraken,
C. L. J Org Chem 1973, 38, 1777.
[17] In Herve’s paper [9] the value pKa = 2.35 was found by
potenciometry. The differences in two pKa values are due to the
different measurement methods as well as to the sensitivity of TNP to
the alkalis used.
[18] Catalan, J.; Abband, J. L.; Elguero, J. Adv Heterocycl Chem
1987, 41, 187.
5‐(4‐Chlorobenzyl)thio‐1‐methyl‐3,4‐dinitro‐1H‐pyrazole (18d).
Yield 90%; mp 80–82°C; IR: 1556, 1540, 1488, 1348, 1316 (NO2)
837 (CCl) cm−1; 1H‐NMR: δ 3.76 (s, 3H, NMe), 4.30 (s, 2H,
CH2), 7.25 (m, 2H), 7.38 (m, 2H); 13C‐NMR: δ 38.21 (NMe,
CH2), 128.97 (CH, C4), 130.87 (CH), 131.07, 135.25 (C5),
136.38, 145.96 (C3); ms: m/z 328, 330 (3:2) (M)+. Anal. Calcd. for
C11H9ClN4O4S: C, 40.19; H, 2.76; N, 17.04. Found: C, 40.56; H,
2.90; N, 17.22.
1‐Methyl‐3,5‐diamino‐4‐nitro‐1H‐pyrazoles 19a,b (general
procedure). A solution of pyrazoles 12b or 12d (2 mmol) and
morpholine or methylamine (as 40% solution in water) (6 mmol)
in MeOH (10 mL) was refluxed for 5 h. In the case of 19a, the
precipitate formed in the reaction mixture was filtered off. In the
case of 19b, the solvent was removed in vacuo, and the residue
was crystallized.
1‐Methyl‐5‐(N‐methylamino)‐3‐(morpholine‐4‐yl)‐4‐nitro‐1H‐
pyrazole (19a). Yield 50%; mp 185–186°C (CH3CN); IR: 3325,
2969, 2952, 2858 (NH), 1629, 1561, 1530, 1455, 1434, 1410,
1
1326 (NO2), 1161, 1110, 1038 cm−1; H‐NMR: δ 3.07 (t, 4H, J
3.0 Hz), 3.13 (d, 3H, J 5.4 Hz, NHMe), 3.67 (t, 4H, J 4.3 Hz),
3.72 (s, 3H, NMe), 7.56 (d, 1H, J 5.2 Hz, NHMe); 13C‐NMR: δ
30.86 (NHMe), 38.08 (NMe), 49.41, 65.68, 111.16 (C4), 148.61
(C5), 151.06 (C3); ms: m/z 241 (M)+. Anal. Calcd. for
C9H15N5O3: C, 44.81; H, 6.27; N, 29.03. Found: C, 45.30; H,
6.35; N, 29.32.
[19] It should be mentioned that salts 3a and 3c were also obtained
in the work by Shreeve [11].
[20] Herve [9] reported that N‐methylation could be achievedusing
methyliodide and NaH in acetonitrile.
[21] Hereafter, the numeration of atoms in XRD data is
differentfrom that of IUPAC rules.
[22] For more detail, see Nelyubina, Y. V.; Dalinger, I. L.;
Lyssenko, K. A. Angew Chem Int Ed 2011, 50, 2892.
[23] Ravi, P.; Gore, G. M.; Venkatesan, V.; Tewari, S. P.; Sikder,
A. K. J Hazard Mater 2010, 183, 859.
1‐Methyl‐3‐(N‐methylamino)‐5‐(morpholine‐4‐yl)‐4‐nitro‐1H‐
pyrazole (19b). Yield 83%; mp 108–110°C (hexane); IR: 3423,
2955, 2852 (NH); 1593, 1509, 1458, 1348 (NO2) cm−1; 1157,
1
1114; H‐NMR: δ 2.82 (d, 3H, J 5.2 Hz, NHMe), 3.12 (t, 4H, J
3.1 Hz), 3.60 (s, 3H, NMe), 3.75 (t, 4H, J 4.0 Hz), 6.50 (br, 1H,
NHMe); 13C‐NMR: δ 28.50 (NHMe), 35.42 (NMe), 48.47, 66.43,
114.25 (C4), 144.75 (C5), 151.06 (C3); ms: m/z 241 (M)+. Anal.
Calcd. for C9H15N5O3: C, 44.81; H, 6.27; N, 29.03. Found: C,
45.21; H, 6.24; N, 29.44.
[24] Schmidt, R. D.; Lee, G. S.; Pagoria, P. F.; Mitchell, A. R.;
Gilardi, R. J Heterocycl Chem 2001, 38, 1227.
[25] According to Herve’s paper [9], TNP reacts with ammonia
at 120ꢀC during 2 h with 100% yield; however, no experimental details
were presented.
REFERENCES AND NOTES
−
[26] NH+4−‐4a HRMS ESI(–) C3H2N5O4 NH+4 m/z: 172.0117 calc.
[1] Boyer, J. H. Nitroazoles; VCH Publishers: Essen, 1986, 368 pp.
[2] Larina, L.; Lopyrev, V. Nitroazoles. Synthesis, Structure and
Applications; Springer, LLC: New York, 2009; p 196.
−
for C3H2N5O4 172.0112; MeNH+3‐4b HRMS ESI(−) C4H4N5O4
−
CH3NH+3 m/z: 186.0272 calc. for C4H4N5O4 186.0269.
[3] Zaitsev, A. A.; Dalinger, I. L.; Shevelev, S. A. Russ Chem Rev
(Engl Transl) 2009, 78, 589.
[4] Dalinger, I. L.; Shevelev, S. A. Russ J Org Chem 1998, 34, 1071.
[5] Dalinger, I. L.; Vatsadze, I. A.; Shkineva, T. K.; Kortusov, I.
O.; Popova, G. P.; Kachala, V. V.; Shevelev, S. A. Russ Chem Bull Int
Ed, 2010, 59, 1786.
[6] Zaitsev, A. A.; Cherkasova, T. I.; Dalinger, I. L.; Kachala, V.
V.; Strelenko, Yu. A.; Shkineva, T. K.; Solkan, V. N.; Shevelev, S. A.
Russ Chem Bull Int Ed 2007, 56, 2074.
[7] Zaitsev, A. A.; Kortusov, I. O.; Dalinger, I. L.; Kachala, V. V.;
Popova, G. P.; Shevelev, S. A. Russ Chem Bull Int Ed 2009, 58, 2118.
[8] (a) Zaitsev, A. A.; Dalinger, I. L.; Starosotnikov, A. A.;
Kachala, V. V.; Strelenko, Yu. A.; Shkineva, T. K.; Shevelev, S. A. Russ
J Org Chem (Engl Transl), 2005, 41, 1507; (b) Zaitsev, A. A.; Vatsadze, I.
A.; Dalinger, I. L.; Kachala, V. V.; Nelyubina, Yu. V.; Shevelev, S. A.
Russ Chem Bull Int Ed 2009, 58, 2109; (c) Zaitsev, A. A.; Zayko, D.
V.; Dalinger, I. L.; Kachala, V. V.; Shkineva, T. K.; Shevelev, S. A. Russ
Chem Bull Int Ed 2009, 58, 2122.
[9] Herve, G.; Roussel, C.; Graindorge, H. Angew Chem Int Ed
2010, 49, 3177.
[10] Dalinger, I. L.; Popova, G. P.; Vatsadze, I. A.; Shkineva, T. K.;
Shevelev, S. A. Russ Chem Bull Int Ed 2009, 58, 2185.
[27] Synthesis and properties 4‐amino‐3,5‐dinitropyrazoles see: (a)
Dalinger, I. L.; Cherkasova, T. I.; Shevelev, S. A. Mendeleev Commun
1997, 58; (b) Lebedev, V. P.; Matyushin, Yu. N.; Inozemtcev, Ya. O.;
Dalinger, I. L.; Shevelev, S. A.; Fomenkov, I. V. Proceedings of 29th
International Annual Conference of ICT, Karlsruhe, FRG, 1998, 180.
[28] Vinogradov, V. M.; Cherkasova, T. I.; Dalinger, I. L.;
Shevelev, S. A. Russ Chem Bull (Engl Transl) 1993, 42, 1552.
[29] According to Herve’s paper [9], TNP reacts with water solu-
tion of 10 equivalents of NaOH at room temperature to give 4‐hydroxy‐
3,5‐dinitropyrazole with 74% yield.
[30] (a) Huang, Z. ‐N.; Li, Z. ‐M. Synth Commun 1995, 25, 3603;
(b) Huang, Z. ‐N.; Li, Z. ‐M. Synth Commun 1996, 26, 3115; (c) Li, Z.;
Li, J.; Jia, G. Heteroatom Chem 1998, 9, 317; (d) Chen, H. S.; Li, Z. ‐M.;
Wang, Z. W. Chin Chem Lett 1999, 10, 643; (e) Abdel‐Megid, M.; Elnagdi,
M. H.; Negm, A. M. J Heterocycl Chem 2002, 39, 105; (f) Cristau, H. ‐J.;
Cellier, P. P.; Spindler, J. ‐F.; Taillefer, M. Eur J Org Chem 2004, 695;
(g) de la Hoz, A.; Diaz, A.; Elguero, J.; Jimenez, A.; Moreno, A.; Ruiz,
A.; Sanchez‐Migallon, A. Tetrahedron 2006, 63, 748; (i) Gerstenberger, B.
S.; Rauckhorst, M. R.; Starr, J. T. Org Lett 2009, 11, 2097.
[31] (a) Bruno, O.; Ranise, A.; Bondavalli, F.; Schenone, P.;
D’Amico, M.; Filippelli, A.; Filippelli, W.; Rossi, F. Farmaco 1993, 48,
949; (b) Huang, Z. ‐N.; Li, Z. ‐M. Gaodeng Xuexiao Huaxue Xuebao
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, S. A. Shevelev, and Y. V. Nelyubina Vol 000
[32] (a) Singer, R. A.; Dore, M.; Sieser, J. E.; Berliner, M. A. Tet-
1995, 16, 1888; (c) Rochais, C.; Lisowski, V.; Dallemagne, P.; Raulf, S.
rahedron Lett 2006, 47, 3727; (b) Withbroe, G. J.; Singer, R. A.; Sieser, J.
E. Org Process Res Dev 2008, 12, 480.
[33] Coburn, M. D. J Heterocycl Chem 1971, 8, 153.
[34] Sheldrick, G. M. SHELXTL_97, Version 5.10, Bruker AXS,
Inc.: Madison, 1997.
Tetrahedron Lett 2004, 45, 6353; (d) Rochais, C.; Sopkova‐de Oliveira
Santos, J.; Dallemagne, P.; Raulf, S. Heterocycles 2006, 68, 2063;
(e) Moss, N.; Breitfelder, S.; Betageri, R.; Cirillo, P. F.; Fadra, T.; Hickey,
E. R.; Kirrane, T.; Kroe, R. R.; Madwed, J.; Nelson, R. M. Bioorg Med
Chem Lett 2007, 17, 4242.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet