Structure and synthesis of 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine

Article abstract of DOI:10.1134/S1070363215070087

A new approach to the synthesis of 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine was developed based on condensing 1-amino-2-nitroguanidine with pentane-2,4-dione under alkaline catalysis. The known method of its preparation in the presence of acetic acid was improved. The structure of 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine was characterized by NMR, IR spectroscopy and X-ray diffraction analysis.

Full text of DOI:10.1134/S1070363215070087

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 7, pp. 1623–1628. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © O.Yu. Ozerova, T.P. Efimova, T.A. Novikova, V.V. Gurzhii, V.M. Berestovitskaya, 2015, published in Zhurnal Obshchei Khimii,
2
015, Vol. 85, No. 7, pp. 1099–1104.
Structure and Synthesis
of 3,5-Dimethyl-N-nitro-1H-pyrazole-1-carboxamidine
a
a
a
b
a
O. Yu. Ozerova , T. P. Efimova , T. A. Novikova , V. V. Gurzhii , and V. M. Berestovitskaya
a
Herzen State Pedagogical University of Russia, nab. reki Moiki 48, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
b
St. Petersburg State University, St. Petersburg, Russia
Received February 16, 2015
Abstract—A new approach to the synthesis of 3,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine was
developed based on condensing 1-amino-2-nitroguanidine with pentane-2,4-dione under alkaline catalysis. The
known method of its preparation in the presence of acetic acid was improved. The structure of 3,5-dimethyl-N-
nitro-1H-pyrazole-1-carboxamidine was characterized by NMR, IR spectroscopy and X-ray diffraction
analysis.
Keywords: 1-amino-2-nitroguanidine, 3,5-dimethyl-N-nitro-1H-pyrazol-1-carboxy-amidine
DOI: 10.1134/S1070363215070087
In recent decades, much attention is paid to
nitro-1H-pyrazole-1-carboxamidine. In [2–5] the reac-
tion time was from 7 to 12 h, and the used temperature
varied from 4 to 25°C; the heterocycle was obtained
with a maximum yield of 80% at room temperature
within 7 h [2].
research in the chemistry of guanidine derivatives.
This is due to the biological activity of compounds
containing guanidine fragment [1], and to the prospect
of the use of its derivatives in the organic synthesis. A
large number of linear and heterocyclic compounds
has been synthesized on the basis of 1-amino-2-nitro-
guanidine. Thus, 3,5-dimethyl-N-nitro-1H-pyrazole-1-
carboxamidine is used as protective group in the
synthesis of aliphatic polyamines (spermidines) in-
volved in the cellular metabolism [2] and also as a
carrier of nitroguanidine moiety in the synthesis of
substituted amino nitroguanidines [3]. Compared with
other protecting groups like N,N'-bis-Boc-1-pyrazole-
We first developed a method of the synthesis of
3
,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine II
under alkaline catalysis. The reaction was carried out
at 65°C for 3 h with equimolar amounts of the
reactants; the yield reaches 55%. We also improved
the procedure for obtaining II in acid catalysis
conditions: slow addition of equimolar amounts of the
reactants at room temperature and maintaining the
reaction mixture for 4 h allowed obtaining the target
compound in 88% yield. In both cases, the formation
of a linear osazone was not observed (Scheme 1).
1
-carboxamidine and N,N'-bis-Boc-N'-triflylguanidine,
the synthesis of 3,5-dimethyl-N-nitro-1H-pyrazole-1-
carboxamidine is more convenient and simple (no use
of inert atmosphere), and its yield is significantly
superior to that of analogs [3].
The structure of 3,5-dimethyl-N-nitro-1H-pyrazole-
1-carboxamidine II was characterized by NMR, IR
spectroscopy and X-ray diffraction data.
According to the literature data, the synthesis of
,5-dimethyl-N-nitro-1H-pyrazole-1-carboxamidine in-
1
3
The H NMR spectrum of compound II contained
volves a classical reaction of 1-amino-2-nitroguanidine
with an excess of a dicarbonyl compound (pentane-
the signals of the protons of all structural fragments. In
a weak field there were characteristic broadened
signals of magnetically nonequivalent protons of the
primary amino group (8.21, 9.08 ppm) due to the
participation of one of the hydrogen atoms of the
amino group in the formation of an intramolecular
2
,4-dione) under acid catalysis (acetic acid [2–5]).
Scott et al. [4] detected the formation of linear osazone
along with the target heterocycle, which leads to a
decrease in the yield of the desired 3,5-dimethyl-N-
1
623

1
624
OZEROVA et al.
Scheme 1.
O
O
H N
NH
2
+
NH2
NNO2
I
а
b
−
+
H O/H ,
H O/OH,
2
2
o
o
4
h, 25 C
3 h, 65 C
O
H N
NH
N
2
N
N
NNO2
H N NNO2
2
II
hydrogen bond with the oxygen of the nitro group. The
singlet of the CH proton of the pyrazole ring was
observed at 6.02 ppm. In a strong field (2.23,
probably attributed to the stretching vibrations of the
C=N bond and bending vibrations of N–H bond,
respectively. The absorption at 1408 and 1240 cm is
–
1
2
.60 ppm) there were the singlets of methyl groups.
due to the stretching vibrations of NO -group [6]. In
2
1
3
The C–{1H} NMR spectrum of II contained the
signals at 112.73, 144.92, and 153.81 ppm belonging
to the carbon atoms of the pyrazole ring. The signals of
the methyl groups were recorded at 13.86 and
the high-frequency part of the spectrum (3332,
–
1
3448 cm ) there was absorption of stretching
vibrations of the N–H bond.
According to XRD data, the nitroamidine moiety,
pyrazole ring, and the methyl groups attached to the
ring lie in the same plane (Fig. 1). In the nitroamidine
fragment, as in other nitrimines [7], there is an intra-
molecular hydrogen bond between the oxygen atom of
1
6.05 ppm. In a weak field (155.81 ppm) there was the
signal of the carbon of nitroamidine fragment. These
findings are consistent with those described in [2].
The IR spectrum of 3,5-dimethyl-N-nitro-1H-pyra-
zole-1-carboxamidine II contained a set of the strong
absorption bands in the range of 1240–1622 cm .
12
9
the nitro group and the amino group (O ···H–N ). Also,
–
1
12
9
12A
the formation of the hydrogen bonds O ···Н–N ···O
makes it possible to combine adjacent molecules into
–
1
Thus, the strong bands at 1622 and 1578 cm can be
Fig. 1. General view of the molecule II. The thermal ellipsoids are represented at the 50% probability level.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 7 2015

STRUCTURE AND SYNTHESIS
1625
Fig. 2. Crystal structure of II. Merging of neighboring molecules in trimers by a system of hydrogen bonds (dashed lines)
1
2
9
12A
[
O ···N ···O ].
Fig. 3. Crystal packing of the molecules II.
3
4
4
5
trimers (Fig. 2). The latter stacked in layers parallel to
the crystallographic plane (11–1) (Fig. 3).
unsubstituted pyrazole: С –С 1.410, С –С 1.369,
1
2
1
5
2
3
N –N 1.366, N –C 1.357, N –C 1.329 Å [8].
EXPERIMENTAL
The bond lengths, bond and torsion angles values
are presented in Tables 1–3. The bond lengths between
3
4
4
5
1
2
the atoms of the pyrazole ring (С –С , С –С , N –N ,
In this research were utilized resources of the
Center for Joint Use of the Herzen Russian State
1
5
2
3
N –C , N –C ) are consistent with the data for the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 7 2015

1
626
OZEROVA et al.
Table 2. Bond angles in the structure of II
Table 1. Bond lengths in the structure of II
Bond
d, Å
Bond
d, Å
Angle
ω, deg
Angle
2B 3B 7B
ω, deg
1
2A– 11A
10B– 11B
O
O
N
N
N
N
N
N
N
C
C
C
C
O
O
N
N
N
N
N
N
1.2489(19)
1.2360(18)
1.3821(19)
1.393(2)
N
N
1.364(2)
1.338(2)
1.420(2)
1.496(2)
1.358(2)
1.491(2)
1.2483(18)
1.2372(19)
1.387(2)
1.396(2)
1.394(2)
1.320(2)
1.311(2)
1.3627(19)
1.333(2)
1.415(2)
1.498(2)
1.360(2)
1.490(2)
2A 1A 5A
N N C
111.84(13) N C C
121.32(16)
127.23(16)
106.97(15)
125.66(16)
105.50(15)
128.83(16)
116.05(15)
131.28(17)
112.67(14)
111.54(14)
117.79(14)
130.65(15)
104.60(14)
118.13(14)
123.13(15)
122.09(14)
114.78(14)
111.56(16)
121.45(16)
126.98(16)
107.07(15)
126.06(16)
105.23(16)
128.70(16)
115.75(16)
131.35(16)
112.90(14)
1
1
1
1
2
9
1
1
3A– 11A
10B– 8B
N
N
C
2A 1A 8A
4B 3B 7B
N N C
117.48(14) C C C
130.68(15) C C C
104.49(14) N C C
117.92(15) C C N
122.97(14) C C C
122.35(14) N C N
114.68(14) N C N
111.62(15)
A– 2A
3B– 4B
N
C
C
C
C
C
5A 1A 8A
5B 4B 3B
C N C
A– 5A
3B– 7B
C
C
3A 2A 1A
1B 5B 6B
C N N
A– 8A
4B– 5B
C
1.398(2)
1.322(2)
1.307(2)
1.3667(19)
1.336(2)
1.418(2)
1.496(2)
1.362(2)
C
8A 10A 11A
4B 5B 1B
C N
N
N
O
N
A– 3A
5B– 6B
C
C
12A 11A 10A
4B 5B 6B
O
O
O
N
A– 8A
12– 11
C
O
O
N
13A 11A 12A
9B 8B 1B
N
0A– 11A
13– 11
N
C
C
C
N
N N
13A 11A 10A
9B 8B 10B
N
0A– 8A
1–
2
2A 3A 4A
10B 8B 1B
N C C
N
C N
3
A– 4A
1–
5
8
3
8
N C
N C
N C
2A 3A 7A
2
1
5
N C C
121.17(16) N N C
127.20(16) N N C
106.73(16) C N C
125.99(15) C N N
105.30(15) C N N
128.70(16) O N N
115.93(15) O N O
131.41(16) O N N
3
4
5
A– 7A
1–
4A 3A 7A
2
1
8
C C C
A– 5A
2–
C
5A 4A 3A
8
1
5
C C C
A– 6A
9–
C
N
N
N
C
C
C
C
1.490(2)
N C
1A 5A 6A
3
2
1
N C C
1
1
1
1
1
2
9
2B– 11B
10– 11
1.2478(18)
1.2346(18)
1.3894(19)
1.394(2)
1.393(2)
1.321(2)
N
N
N
4A 5A 1A
8
10 11
C C N
3B– 11B
10–
8
C
4
4A 5A 6A
12 11 10
C C C
B– 2B
3–
C C
9A 8A 1A
13 11 12
N C N
B– 5B
3–
7
5
6
C C
9A 8A 10A
13 11 10
N C N
B– 8B
4–
C C
10A 8A 1A
2
3
4
7
N
C N
112.66(15) N C C
B– 3B
5–
C C
2B 1B 5B
2
3
N N C
111.48(14) N C C
117.67(14) C C C
130.83(14) C C C
104.60(14) N C C
117.86(14) C C N
123.13(14) C C C
122.02(15) N C N
114.85(14) N C N
B– 8B
1.307(2)
2B 1B 8B
4
3
7
3
6
N N C
8
B
1B 5B
5
4
C N C
3
B
2B 1B
1
5
Pedagogical University. X-Ray studies were performed
in the X-ray Diffraction Centre of St. Petersburg State
University.
C N N
8
B
10B 11B
4
5
1
C N
N
N
O
N
1
1
1
2B 11B 10B
4
5
6
O
O
O
N
3B 11B 12B
9
8
1
N
NMR spectra (CDCl ) were recorded on a Jeol
ECX400A instrument operating at 399.78 ( H) and
00.52 ( C) MHz using the residual signals of
undeuterated solvent as internal reference. IR spectra
chloroform) were obtained on a Shimadzu IRPrestige-
3
3B 11B 10B
9
8
10
1
1
N
1
3
2B 3B 4B
10
8
1
N C C
111.44(15) N C N
(
2
Synthesis of starting 1-amino-2-nitroguanidine I
was performed as described in [12].
1 FTIR spectrometer.
XRD studies were performed on a single-crystal
3
,5-Dimethyl-N-nitro-1H-pyrazole-1-carboxamidine
diffractometer Agilent Technologies Excalibur Eos
equipped with a CCD detector. Measurements were
performed at 100 K using monochromated MoKα-
irradiation. The unit cell parameters (Table 4) were
refined by the least squares method based on the 10439
reflections with 2θ in the range of 5.52°–55.00°. The
structure was solved by the direct method and refined
to R 0.047 (wR 0.096) for 4262 independent reflec-
(
II). a. Under acid catalysis conditions. Pentane-2,3-
dione (0.43 mL, 0.0042 mol) and a catalytic amount of
acetic acid were added dropwise to a solution of 0.5 g
(
0.0042 mol) of 1-amino-2-nitroguanidine in 10 mL of
water. The reaction mixture was stirred at 25°C for
h. The resulting precipitate was filtered off, washed
4
successively with water, ethanol, and diethyl ether, and
dried in air. Yield 0.68 g (88%), mp 112–113°C
(
1
2
tions with |F | ≥ 4σ using SHELXL-97 [9] and
0
F
i-PrOH) {mp 127–128°C (EtOH) [2]}. Found N, %:
OLEX2 [10] software. The correction for extinction
was made by CrysAlisPro program [11]. Positions of
the hydrogen atoms were calculated with use of
SHELX package. The crystallographic data were
deposited at Cambridge Crystallographic Data Center
3
8.25. C H N O . Calculated N, %: 38.32.
6
9
5
2
The synthesis by the literature method [2] provided
compound II in a 80% yield , as described; however,
its melting point was 112–113°C, not 127–128°C as
indicated in [2]. The mixed test with the sample
(
CCDC 1,037,784).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 7 2015

STRUCTURE AND SYNTHESIS
Table 4. Crystallographic data of compound II
1627
Table 3. Torsion angles in the structure of II
Angle
τ, deg
Angle
τ, deg
Parameter
Value
1
A
2A 3A 4A
3B 4B 5B 6B
N N C C
0.41(19)
–179.19(15) C N N C
C C C C
178.60(17)
–0.36(18)
–178.50(17)
0.8(3)
–179.35(17)
178.51(15)
–178.18(17)
2.8(3)
Empirical formula
Crystal system
a, Å
C H N O
2
6
9
5
1
A
2A 3A 7A
5B 1B 2B 3B
N N C C
Triclinic
2
A
1A 5A 4A
5B 1B 8B 9B
N N C C
0.96(19)
–178.52(16) C N C N
3.2(2)
–176.96(14) C N N C
0.2(2)
C N C N
8.5457(7)
11.8721(8)
12.6530(7)
105.533(5)
93.338(6)
92.345(6)
1232.61(14)
183.18
2
A
1A 5A 6A
5B 1B 8B 10B
7B 3B 4B 5B
N N C C
b, Å
2
A
1A 8A 9A
N N C N
C C C C
c, Å
2
A
1A 8A 10A
8B 1B 2B 3B
N N C N
α, deg
2
A
3A 4A 5A
8B 1B 5B 4B
N C C C
C N C C
β, deg
1
1A 10A 8A 1A
8B 1B 5B 6B
N
N
N
N
C N 176.25(14) C N C C
C N –3.9(3)
γ, deg
1
1A 10A 8A 9A
8B 10B 11B 12B
C N
N
O
O
–5.4(2)
3
V, Å
3
A
4A 5A 1A
8B 10B 11B 13B
C C C N
–0.66(19)
178.80(18) N N C C
C N
N
174.98(15)
–0.11(19)
178.79(16)
–0.1(2)
–179.52(17)
–1.4(2)
177.70(14)
0.0(2)
177.42(14)
–3.7(3)
М
3
A
4A 5A 6A
1
2
3
4
7
4
6
9
C C C C
Space group
P-1
5
A
1A 2A 3A
1
2
3
C N N C
–0.85(18)
–176.24(17) N N C C
3.6(3)
179.74(17) N N C N
179.63(15) N N C N
–179.60(17) N C C C
0.9(3)
–2.1(2)
N N C C
–
1
μ, cm
Т, K
Z
0.116
5
A
1A 8A 9A
2
1
5
C N C N
100(2)
5
A
1A 8A 10A
2
1
5
C N C N
N N C C
6
7
A
3A 4A 5A
2
1
8
C C C C
8
A
1A 2A 3A
2
1
8
10
d
calc, g/cm
1.481
C N N C
3
8
A
1A 5A 4A
2
3
4
5
Crystal size, mm
Radiation
0.32×0.24×0.15
C N C C
8
A
1A 5A 6A
11 10
8
1
9
MoK
α
C N C C
N N C N
8A
10A 11A 12A
11 10
8
Reflections collected
Independent reflections
2θ range, deg
10439
5663
C N
N
N
O
O
N N C N
8A
10A 11A 13A
3
4
5
1
C N
178.62(15) C C C N
0.0(2)
1B
2B 3B 4B
3
4
5
6
5.52–55.00
4262
N N C C
0.08(19)
179.68(15) C N N C
0.49(19)
–178.57(16) C N C N
2.9(2)
–177.79(14) C N N C
0.2(2)
C C C C
179.44(18)
0.13(19)
176.97(16)
–3.9(3)
–178.77(17)
178.81(15)
–178.56(17)
2.0(3)
1B
2B 3B 7B
5
1
2
3
0 F
Reflections with |F | ≥ 4σ
N N C C
2B
1B 5B 4B
5
1
8
9
R
R
R
int
0.0263
N N C C
C N C N
2B
1B 5B 6B
5
1
8
10
N N C C
σ
0.0521
2B
1B 8B 9B
7
3
4
5
N N C N
C C C C
1
(|F
(|F
(all data)
0
| ≥ 4σ
F
)
0.0475
2B
1B 8B 10B
8
1
2
3
N N C N
wR
2
0
| ≥ 4σ
F
)
0.0961
2B
3B 4B 5B
8
1
5
4
6
N C C C
C N C C
R
1
0.0698
1B
10B 8B 1B
8
1
5
N1 N C N 178.85(14) C N C C
wR (all data)
0.1067
2
1
1B 10B 8B 9B
8
10 11 12
N N C N –2.0(3)
C N N O
1.6(2)
–178.38(16)
S
1.037
3B
4B 5B 1B
8
10 11 13
3
C C C N
–0.41(19)
C N N O
rmin, rmax, e/Å
–0.307, 0.248
obtained via the method a did not show any depression
ACKNOWLEDGMENTS
of the melting point.
This work was financially supported by the
Ministry of Education and Science of the Russian
Federation in the frame of the base part of the
governmental contract.
b. Under alkaline catalysis conditions. Pentane-2,3-
dione (0.43 mL, 0.0042 mol) was added dropwise to a
solution of 0.5 g (0.0042 mol) of 1-amino-2-nitro-
guanidine and 0.23 g (0.0042 mol) of potassium
hydroxide in 10 mL of water. The reaction mixture
was heated to 65°C and stirred for 3 h, then cooled to
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