New synthetic route to diaminonitropyrazoles as precursors of energetic materials

Article abstract of DOI:10.1016/S0040-4039(03)01301-7

Treatment of nitropyrimidine derivatives with (N-substituted) hydrazines (2 equiv.) gave 1-(substituted)-3,5-diamino-4-nitropyrazole, providing a very mild conversion of pyrimidines into pyrazoles. This reaction provided a convenient route to precursors for new efficient and insensitive explosives.

Full text of DOI:10.1016/S0040-4039(03)01301-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5943–5945
New synthetic route to diaminonitropyrazoles as precursors of
energetic materials
J e´ r oˆ me Guillard, Fanny Goujon, Perrine Badol and Didier Poullain*
CEA Le Ripault BP 16 37260 Monts, France
Received 4 March 2003; revised 12 May 2003; accepted 26 May 2003
Abstract—Treatment of nitropyrimidine derivatives with (N-substituted) hydrazines (2 equiv.) gave 1-(substituted)-3,5-diamino-4-
nitropyrazole, providing a very mild conversion of pyrimidines into pyrazoles. This reaction provided a convenient route to
precursors for new efficient and insensitive explosives.
©
2003 Elsevier Ltd. All rights reserved.
Currently, in the field of explosives research, emphasis
is given to high quality simple compounds with high
energy, high density, heat resistance and low sensitivity.
Synthesis and structural characterization of new insen-
sitive energetic compounds with these properties is the
4-methyl-s-triazine by potassium amide in liquid
ammonia.
6
In this paper, we describe the reaction of N-substituted
hydrazines with 4-(substituted)-6-chloro-5-nitropyrim-
idines in order to discover new precursors of energetic
compounds (Scheme 1).
1
focus of studies in our laboratory.
A literature survey reveals that many energetic com-
1
2
pounds containing pyrimidine and pyrazole rings are
of multi-purpose interest since the heterocyclic skeleton
with nitrogen content confers a high enthalpy of forma-
tion and thermal stability. Many papers were devoted
to reactions of substituted pyrimidines with nucle-
The attack on 4,6-dichloro-5-nitropyrimidine by (N-
substituted)-hydrazines gave the dihydrazino com-
pounds A , A and A with low to moderate yields,
1
2
4
except with the benzylhydrazine A (Table 1). In this
3
latter case, only one chlorine atom was substituted by
benzylhydrazine. The action of (N-substituted)-hydrazi-
nes on 4-amino-substituted pyrimidines derivatives led
to ring opening and 1-substituted-3,5-diamino-4-
nitropyrazoles were obtained. This ring transformation
proceeded by a mechanism not get reported in pyrim-
3
–5
ophiles causing ring contraction such as conversion
4
of urazil into pyrazolone and urea by hydrazine, con-
version of 4-methoxy-5-nitropyrimidine into 3-amino-4-
5
nitropyrazole by the same reagent, and transformation
of 2-substituted-4-chloropyrimidine into 2-substituted-
Scheme 1.
Keywords: hydrazine; nitropyrazoles; nitropyrimidines.
*
Corresponding author. Fax: 02 47 34 51 42; e-mail: poullain@ripault.cea.fr
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01301-7

5
944
J. Guillard et al. / Tetrahedron Letters 44 (2003) 5943–5945
Table 1. Synthesis of 4,6-di(substituted)hydrazino-5-nitropyrimidines and 1-substituted-3,5-diamino-4-nitropyrazoles from 4-
substituted)-6-chloro-5-nitropyrimidines
(
R1
R2
R3
Product
Time (min)
Yield (%)
Mp (°C)
Temperature of decomposition (°C)
7
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
CH3
Bn
SO Ph
H
CH3
H
H
A1
30
30
30
60
80
180
60
40
60
54
11
97
37
57
54
21
27
61
186
189
225
212
A2
A3
A4
2
8
N(CH3)2
N(CH3)2
Morpholino
NH(CH ) CH
3
B1
260–262
186–188
B2
B1
A5
B1
255–256
2
3
N(CH3)2
OMe
H
idine chemistry (Scheme 2). The yields of pyrazoles
obtained from 4-N,N-dimethyl substituted pyrimidines
showed that this is the better leaving group used.
In view of these results, the impact sensitivity of A and
1
A was measured with a drop weight impact test (11
4
9
kg). Under these test conditions, Octogene (HMX) was
readily detonated with a hammer’s height of 12 cm.
Compounds A and A could not be detonated with this
Moreover, with a butylamino group in position 4, the
reaction stopped at the first step of the rearrangement,
i.e. the substitution of hydrazine in position 6. The
butylamino group may stabilize the pyrimidine system
to prevent the second attack of hydrazine in position 2.
The rearrangement of 4-N,N-dimethyl-5-nitro-6-
methoxypyrimidine with hydrazine hydrate shows that
a methoxy group instead of a chlorine atom in position
1
4
test despite numerous attempts, and are thus less sensi-
9
tive to impact than Pentrite or Octogene.
In conclusion, we have described the reactivity of N-
substituted hydrazines with nitropyrimidines. The reac-
tion between 4-(substituted)-6-(chloro or methoxy)-
pyrimidines and hydrazine hydrate leads, in one step
with a previously undescribed mechanism, to 1-(substi-
tuted)-3,5-diamino-4-nitropyrazoles. As a result, this
reaction provides a convenient route to some precursors
for new insensitive explosives.
6
does not affect the yield of 3,5-diamino-4-nitropyra-
zole that much. Therefore, a chlorine atom and a
methoxy group have the same reactivity in this
rearrangement.
Experimental section
The opening of the pyrimidine ring involves a nucle-
ophilic attack by hydrazine on position 2 of the hydra-
zino derivatives, with scission of the 2–3 bond and
generation of a cyano group. The resulting acyclic
intermediate undergoes an intramolecular nucleophilic
attack on the cyano group by the 6-hydrazino group,
which results in the formation of a pyrazole ring.
Melting points were determined on a Kofler melting
point apparatus and are uncorrected. Differential Scan-
ning Calorimetric (DSC) analyses were recorded with a
DSC 822 Mettler apparatus by heating a sample at a
rate of 10°C/min in the presence of static air. IR spectra
were recorded on a Perkin–Elmer Spectrum One FT-IR
spectrometer with a Perkin Elmer Universal ATR sam-
pling accessory. NMR spectra were recorded on a
Br u¨ ker Avance 200 MHz NMR. The chemical shifts in
CDCl and DMSO-d are reported in l (ppm). Mass
Differential Scanning Calorimetric (DSC) analyses of
A and A have shown that compound A exhibits a
1
4
1
broad exothermic peak at 186°C, while compound A4
exhibits a high energetic single sharp exothermic peak
at 212°C.
3
6
spectra were recorded on a HP 5973 mass spectrometer
in the Faculty of Pharmacy of Tours, France.
Scheme 2.

J. Guillard et al. / Tetrahedron Letters 44 (2003) 5943–5945
5945
General procedure for the synthesis of dihydrazino
zine hydrate (4.5×2 mmol). The mixture was stirred
under reflux until the starting material was fully con-
verted (TLC). After cooling the mixture, the precipitate
obtained was filtered off, and washed with hot ethanol.
compounds:
To a solution of a 4,6-dichloro-5-nitropyrimidine (500
mg, 2.6 mmol) in methanol was added dropwise hydra-
zine hydrate (0.63 mL, 4.5×2.6 mmol). The mixture was
stirred at room temperature for 30 min. The precipitate
obtained was filtered off and purified by recrystalliza-
tion from isopropanol.
1-Methyl-3,5-diamino-4-nitropyrazole B2 (R =CH ).
6
3
−
1
Yellow needles, mp 186–188°C; wmax (cm ) 3411, 3293,
1614, 1571, 1493, 1413, 1380, 1225, 1166, 1126, 1087;
lH (200 MHz, DMSO-d ) 3.34 (s, CH ), 5.87 (s, 2H,
6
3
NH ), 7.20 (s, 2H, NH ); l (50.47 MHz, DMSO-d )
2
2
C
6
+
+
4
,6-Dimethylhydrazino-5-nitropyrimidine A (R =R =
34, 108, 145, 149; 160 m/z 157 (M , 55%), 127 (M −
[NO], 9), 96 (M −[NO +Me], 20), 65 (100), 43 (41).
2
4
5
−
1
+
NHNHCH ). Orange needles, mp 189°C; wmax/cm
3
2
3
8
4
335, 3285, 1630, 1567, 1521, 1506, 1484, 1398, 936,
63; lH (200 MHz, DMSO-d ) 3.20 (s, 6H, 2×CH ),
6
3
.62 (s, 4H, 4×NH), 7.91 (s, 1H, Harom).
Acknowledgements
4
-Benzylhydrazino-5-nitro-6-chloropyrimidine A (R =
3
4
NHNHBn, R =Cl). Yellow needles, mp 225°C; wmax/
cm 3333, 2921, 1643, 1565, 1531, 1495, 1465, 1454,
We thank the Laboratoire de caract e´ risation Physico-
Chimique (LPC) for the assistance in recording the
NMR spectra, the Laboratoire de Caract e´ risation
R e´ active (LCR) for the impact sensitivity tests and
DGA for financial support.
5
−
1
1
3
5
407, 1345, 1300, 1255, 1027; lH (200 MHz, CDCl3)
.65 (s, 2H, CH Ph), 5.02 (s, 2H, 2×NH), 7.18–7.39 (m,
2
+
H, Harom), 8.33 (s, 1H, H
); m/z 279 (M , 4%), 216
arom
+
(
9), 91 ([CH Ph] , 100), 65 (25).
2
4
,6-Dibenzylsulfonylhydrazino-5-nitropyrimidine
A4
References
(
R =R =NHNHSO Ph). Yellow needles, mp 212°C;
wmax/cm 3338, 3254, 3061, 1576, 1521, 1497, 1448,
408, 1350, 1301, 1229, 1212, 1180, 1167, 1090; l (200
4
5
−
2
1
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1
H
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4
NHNH , R =NH(CH ) CH ). Orange needles, mp
2
5
2 3
3
−
1
2
1
1
55–256°C; wmax/cm 3334, 3272, 2953, 2935, 2871,
587, 1553, 1525, 1506, 1477, 1458, 1366, 1347, 1262,
245, 1223, 1159, 1122, 1076, 967, 946, 782; lH (200
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3
CH ), 1.57 (s, 2H, NH ); 1.68 (sextuplet, 2H, CH ),
2
2
2
3
.67 (quadruplet, 2H, CH -N), 8.24 (s, 1H, Harom), 9.37
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2
(d, 1H, NH-CH ), 12.37 (s, 1H, NH-NH ); l (50.47
2
2
C
MHz, CDCl ) 14, 20, 31, 42, 149, 160.
3
7. Knakov, M. H.; Christensen, B. E. J. Org. Chem. 1963, 28,
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compounds:
2677.
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To a warm solution of 4,6-substituted-5-nitropyrim-
idine (2 mmol) in ethanol was dropwise added hydra-