Four syntheses of 4-Amino-3,5-dinitropyrazole

Article abstract of DOI:10.1002/jhet.1725

In this paper, syntheses of 4-amino-3,5-dinitropyrazole from four different starting materials are described. The starting materials were 4-nitropyrazole, 4-nitro-3,5-dimethylpyrazole, 3,5-dinitropyrazole, and 4-chloropyrazole, respectively. They are compared in terms of yield, number of steps and suitability for scale-up into pilot scale production. The overall yield, calculated from commercially available starting materials, ranged from 21% in the case of synthesis via 3,5-dinitropyrazole up to 61% for the one starting from 4-chloropyrazole. With numerous factors taken into account, the latter was chosen for a pilot scale study and the product could be produced in batches of 200 g.

Full text of DOI:10.1002/jhet.1725

Month 2014
Four Syntheses of 4-Amino-3,5-dinitropyrazole
a
Stefan Eka,b and Nikolaj V. Latypov
*
aDepartment of Energetic Materials, Swedish Defence Research Agency, FOI, Grindsjön Research Centre, SE-172 90
Tumba, Sweden
bDepartment of Biosciences and Nutrition, the Karolinska Institute, Novum, 141 83 Huddinge, Sweden
*
E-mail: stefan.ek@foi.se
Received January 12, 2012
DOI 10.1002/jhet.1725
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
In this paper, syntheses of 4-amino-3,5-dinitropyrazole from four different starting materials are described. The
starting materials were 4-nitropyrazole, 4-nitro-3,5-dimethylpyrazole, 3,5-dinitropyrazole, and 4-chloropyrazole,
respectively. They are compared in terms of yield, number of steps and suitability for scale-up into pilot
scale production. The overall yield, calculated from commercially available starting materials, ranged from
21% in the case of synthesis via 3,5-dinitropyrazole up to 61% for the one starting from 4-chloropyrazole. With
numerous factors taken into account, the latter was chosen for a pilot scale study and the product could be
produced in batches of 200 g.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
and nitro groups, which can be found in energetic materials
with low sensitivity, e.g. 1,3,5-triamino-2,4,6-trinitrobenzene
and 1,1-diamino-2,2-dinitroethylene (DADNE, FOX-7) [3].
5-Nitro-1,2,4-triazol-3-one is also a highly insensitive
explosive, but it has no electron donating groups in its
structure. Although it has strong intermolecular hydrogen
bonding that appears to increase the stability towards
thermal and mechanical stimuli.
The aforementioned factors directed our attention towards
nitropyrazoles, which have favorable properties, such
as high thermal stability and high energetic potential.
Furthermore, they can be substituted in no less than four
positions, i.e. on the three carbons and also on one of
the nitrogens, which allows a large variety of derivatives.
This work deals with 4-amino-3,5-dinitropyrazole (1),
which is an example of a pyrazole with alternating nitro and
amino groups (Scheme 1). Protected 1 was first prepared by
Vinogradov et al. [4] in a synthesis with six steps. The parent
compound 1 was later presented by Shevelev et al. [5].
Schmidt et al. [6] published a shorter synthesis in 2001, which
used vicarious nucleophilic substitution (VNS) of hydrogen
Nitroaromatics, such as picric acid and 2,4,6-trinitrotoluene
(TNT), have been used as explosives throughout the last
century. Non-aromatic explosives, mainly cyclic nitramines
such as 1,3,5-triaza-1,3,5-trinitrocyclohexane (RDX) and
1,3,5,7-tetraaza-1,3,5,7-tetranitrocyclooctane (HMX) are also
in use. The different classes of compound have their
advantages and drawbacks, respectively. Compared with
the nitramines, TNT has relatively low sensitivity to
mechanic stimuli and thus to involuntary detonation, but
relatively low oxygen content and heat of formation,
which are important factors in the force of an explosive.
RDX and HMX have higher energy and oxygen content,
thanks to the carbons being exchanged for nitrogen, and
also higher sensitivity to mechanical stimuli.
The combination of higher energy content and lower
sensitivity is often desired. The former can be calculated
[1,2], whereas the latter is difficult to predict. However,
there are some features that seem to have a beneficial
effect. One such is alternating electron donating groups
© 2014 HeteroCorporation

S. Ek and N. V. Latypov
Vol 000
Scheme 1. A schematic view of the four syntheses of 4-amino-3,5-
dinitropyrazole.
product with ammonia at different temperatures add two
steps to the transformation of 3,5-dinitropyrazole into 4-
amino-3,5-dinitropyrazole, in comparison with Schmidt’s
procedure, which only adds one [6]. To allow a full evalua-
tion of a substance, the synthesis should be possible to
perform in at least multigram and preferably in kilogram
scale. This made us look deeper into new, more efficient,
and straightforward synthetic pathways.
RESULTS AND DISCUSSION
Synthesis 1 (Scheme 2): 4-Amino-3,5-dinitropyrazole via
3,5-dinitropyrazole.
One of the major drawbacks in
Schmidt’s synthesis [6] is the use of the toxic 1,1,1-
TMHI. Therefore, other VNS reagents were evaluated.
One first attempt with hydroxylamine in methanol failed.
However, the combination of 4-amino-1,2,4-triazole (6)
and potassium tert-butoxide in anhydrous DMSO
produced 1 in 82% yield (Scheme 2). 4-Amino-1,2,4-
triazole has two advantages in comparison with TMHI. It
is commercially available and considerably less toxic
than the chemicals involved in the production of TMHI.
This reaction worked efficiently with higher yield (82%)
than the previously published procedure [6] (67%) and
provided a pure DMSO solvate of the desired product.
This synthesis has five steps starting from pyrazole. In
our hands, the published procedure [7,10], with minor
modifications, produced 4 in 27% yield from pyrazole.
This resulted in an overall yield of 21%.
in 3,5-dinitropyrazole (4). This last step of this elegant
synthesis involves the toxic reagent trimethylhydrazinium
iodide (TMHI). Another drawback is the tedious synthesis
of the starting material 4, which includes four steps and
was described by Jansen et al. in 1973 [7]. The high ther-
mal stability and moderate sensitivity to impact of 1 makes
it an interesting candidate as a new energetic material. The
synthesis presented by Hervé et al. [8] and Dalinger et al.
[9] in 2010 uses 3,5-dinitropyrazole, whose drawbacks are
mentioned earlier, as their starting material. Nitration of this
product into 3,4,5-trinitropyrazole and reaction of the
Synthesis 2 (Scheme 3): 4-Amino-3,5-dinitropyrazole via 4-
nitropyrazole.
To reduce the number of steps in the
synthesis, another route was envisaged. This synthesis is
outlined in Scheme 3. The nitration of pyrazole into
4-nitropyrazole (2) was nearly quantitative (95%). The
reduction of the latter in aqueous, basic sodium dithionite
solution [11] to afford 4-aminopyrazole (7), protected as
a carbamate (8), had a yield of 60%. The reduction and
protection is a one-pot procedure. Counting this as
one step resulted in four-step procedure starting from
pyrazole, i.e. one step less than Schmidt’s synthesis,
Scheme 2. Synthesis 1, 4-amino-3,5-dinitropyrazole via vicarious
nucleophilic substitution (VNS).
Scheme 3. Synthesis 2, 4-amino-3,5-dinitropyrazole from 4-nitropyrazole.
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vide supra. Nitration resulted in a highly hygroscopic
product (9) in 95% yield.
protected as a carbamate (12), which allowed nitration in
mixed acids, see Scheme 4.
The removal of carbamates, by the use of different
methods [12–17], has been described in the literature.
The hydrolysis was first attempted in refluxing
40% aqueous potassium hydroxide, as indicated by
Shevelev et al. [5] for the corresponding methyl carbamate,
and then 35% hydrochloric acid. In the basic solution, the
conversion was a few percent after 72-h refluxing. The
acidic treatment yielded a complex mixture of products.
To avoid the risk of nitro group substitution by chloride
ions, 9 was heated in 60% sulfuric acid overnight to
remove the protective group. Recrystallization of the
extracted product from water produced the hydrate of the
desired product in 70% yield. The overall yield, from
pyrazole into 1, of this procedure was 40%.
One problem encountered in this synthetic sequence is
the high solubility of the intermediate carboxylic acids
(11 and 12). Oxidation of 3 into 11 proceeded in 60%
yield, when 11 was isolated in its pure form. The oxidation
is carried out in basic potassium permanganate solution.
After the completion of the reaction, the manganese diox-
ide was removed by filtration. The filtrate was concentrated
and neutralized, which resulted in precipitation of 11 in
yields as described earlier, vide supra. However, further
concentration of this filtrated provided more, but impure
product. The major impurity was potassium chloride,
which did not disturb the following step. The yield of 12
from 3 was 72% (two steps), which is considerably higher
than it would have been with isolation of the intermediate.
The nitration-decarboxylation into protected 9 took place in
mixed acids in quantitative yield. Since this procedure
resulted in the same intermediate 9 as described earlier, the
hydrolytic removal of the protective group was performed
in the same way, vide supra. The overall yield from
3,5-dimethylpyrazole to 1 was 37%, which the authors
considered as excellent, considering the number of steps
in the reaction.
Synthesis 3 (Scheme 4). 4-Amino-3,5-dinitropyrazole from
3,5-dimethylpyrazole. The synthesis via decarboxylation-
nitration outlined in the succeeding text, compared with
Scheme 4, had more steps than the ones already described,
vide supra, but it has the advantage to use the inexpensive
and commercially available 3,5-dimethylpyrazole as its
starting material. This compound was readily nitrated in
mixed acids at ambient temperature to give corresponding
4-nitro derivative (3), which could be oxidized [18] to
4-nitropyrazole-3,5-dicarboxylic acid (10) in 60% yield.
The latter compound was reduced with sodium dithionite
to 4-aminopyrazole-3,5-dicarboxylic acid (11), as described
by Redemann [11].
Synthesis 4 (Scheme 5). 4-Amino-3,5-dinitropyrazole from
4-chloropyrazole. In another attempt to reduce the number
of steps, a synthesis starting from 4-halopyrazoles
was outlined, see Scheme 5, where the case of
4-chloropyrazole (5) is shown.
Compound 11 was subjected to nitration by mixed acids
with the intention to supply the desired product. However,
this procedure produced a bright red mixture of unidenti-
fied products. To prevent N-nitration, diazotisation or any
other side reaction, the exocyclic amino group was
One example of synthesis of dinitropyrazoles in a single
step was reported by Coburn [19] in his studies on nitra-
tion of 1-methyl-4-substituted pyrazoles, see Scheme 6.
This can be contrasted to the exclusive formation of
4-nitropyrazole upon nitration of pyrazole itself [7,10,20].
Scheme 4. Synthesis 3, 4-amino-3,5-dinitropyrazole from 4-nitro-3,5-dimethylpyrazole.
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Scheme 5. Synthesis 4, 4-amino-3,5-dinitropyrazole from 4-chloropyrazole.
Scheme 6. Coburn’s dinitrations of substituted pyrazoles [19].
Perevalov [21] et al. studied the product distribution in
the nitration of 1-methyl-4-bromo- (14) and 1-methyl-4-
chloropyrazole (15), see Scheme 7. It was shown that
14 underwent dehalogenation/ipso-nitration in position 4
to different extents depending on the reaction conditions.
15, on the other hand, did not undergo any such side reac-
tion. Therefore, nitration of 5 was evaluated, which yielded
13 in 83% yield.
The sublimed product was white, in comparison with the
commercial brownish product. The NMR spectrum of the
former displayed a doublet peak for the two aromatic
protons, whereas the latter only had a singlet. Heat had to
be applied to merge the doublet of the sublimed product
into a singlet. Only a singlet could be observed when
pyrazole was chlorinated with chlorine gas in acetic acid
in an early, unsatisfactory attempt to obtain pure 5.
The commercially available 5 was only approximately
90% pure. To our delight, the impurities oxidized in the
nitration mixture and the obtained 13 could be used with-
out further purification. To establish the yield, pure 5 had
to be prepared. This was obtained via chlorination of
pyrazole with sodium hypochlorite in dilute hydrochloric
acid, followed by sublimation of the obtained product.
The aromatic, nucleophilic substitution of 13 with
aqueous ammonia into 1 took place in a sealed vessel at
high temperature (130 ꢀC, 11 atm). The reaction produced
the ammonium salt of 1. Recrystallization from acidic
water yielded the hydrate of 1. After azeotropic removal
of the crystal water, the yield of 1 was 73% from 13.
The overall yield of this procedure was 61% from 5.
Scheme 7. Perevalov’s nitrations of 1-methyl-4-halopyrazoles [21].
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Table 1
A brief comparison of the different synthetic procedures.
Synthesis 1: Via 3,5-dinitropyrazole Synthesis 2: Via 4-nitropyrazole
Synthesis 3: From 3,5-dimethyl-
pyrazole (cf. Scheme 4)
Synthesis 4: From 4-chloropyrazole
(cf. Scheme 5)
(cf. Scheme 2)
(cf. Scheme 3)
Five steps
Four steps
Six steps
Two steps
Moderate amount of waste
DMSO used in the last step
Moderate amount of waste
No unfavorable solvents
required
High amount of waste
No unfavorable solvents
required
Small amount of waste
No unfavorable solvents
required
Low overall yield: 21%
Average yield/step: 73%
Moderate overall yield, 40%
Average yield/step: 80%
Moderate overall yield: 37%
Average yield/step: 85%
Moderate overall yield: 61%
Average yield/step: 78%
Comparison of the different syntheses. The choice of
starting point will greatly influence any comparison of
the different syntheses of 4-amino-3,5-dinitropyrazole.
Our choice was to start from readily commercially
available starting materials at the time of the start of this
study. Therefore, pyrazole is considered the starting point
in the two first syntheses, 3,5-dimethylpyrazole in the
third and 4-chloropyrazole in the last, vide supra. The
advantages and disadvantages of the different syntheses
are shown in Table 1 and compared in the succeeding
paragraphs, vide infra.
CONCLUSIONS
Four different syntheses of 1 were developed and
compared in terms of overall yield, number of steps,
and production of waste. One of them, namely the nitra-
tion of 5 followed by aromatic nucleophilic substitution
with ammonia, produced 1 in batches of up to 200 g.
Compound 1 as such could be used as an explosive, or
as a starting material for even more energetic and/or
complex structures.
The longest synthesis by these means is Synthesis 3
(Scheme 4), i.e. the one starting from 3,5-dimethylpyrazole
with six steps. Syntheses 1 and 2 (Schemes 2 and 3), both
starting from pyrazole, have five and four steps, respec-
tively. The shortest is Synthesis 4 (Scheme 5), starting
from 4-chloropyrazole with only two steps.
EXPERIMENTAL
General. The H and 13C NMR spectra were recorded at
1
400 MHz and 100 MHz, respectively, on a Bruker Avance
400 spectrometer (Bruker AG, Fällanden, Switzerland). UV/VIS
spectra were recorded on a Perkin Elmer Lambda 650 (Perkin
Elmer, Bucks, UK). Melting points were determined on a
Mettler DSC30 (Mettler-Toledo, Schwerzenbach, Switzerland).
The overall yields of the different procedure ranged from
21% in the Synthesis 1 (Scheme 2) via 3,5-dinitropyrazole
up to 61% in Synthesis 4 (Scheme 5) from 5. Keeping this in
mind, only Synthesis 1 (Scheme 2) via 4 can be discarded.
The other three procedures, all have yields between 37 and
61%. This little difference means that other factors must
be used in the selection of a procedure suitable for scale-up.
Two such factors, besides the number of steps outlined
earlier, are choice of solvents and production of waste.
DMSO is generally a difficult solvent to purify, because
it is freely miscible with water and must be anhydrous in
many reactions. This renders it less favored by industry.
This is the main obstacle of the synthetic step from 4 to 1
used in the first procedure. Sodium dithionite is used in
Synthesis 2 (Scheme 3) and 3 (Scheme 4). This reagent
has to be used in large excess and cannot be easily reused
or recycled. This reagent can thus only be used in small
scale. Synthesis 3 (Scheme 4) includes an oxidation with
potassium permanganate, which produces much waste.
The only procedure using suitable solvents and not produc-
ing excessive waste is Synthesis 4 (Scheme 5), starting
from 5. This procedure was successfully scaled up to small
pilot plant scale. The limiting factor in this case was the
size of our pressure reactor. Nonetheless, 200 g of 1 could
be produced in one single batch.
3,5–Dinitropyrazole (4). 3-Nitropyrazole (6.9 g, 61 mmol)
[10] was suspended in acetic anhydride (20 mL) and cooled in
an ice-bath. To this suspension, nitric acid (3.8 mL, d 1.52, 91.7
mmol) was added under vigorous mixing and at such a rate that
the temperature was maintained below +10 ꢀC. The mixture was
kept at this temperature for an additional 2 h. The starting
material dissolved completely during this time. The resulting
solution was poured into ice water (100 mL). The oily product
crystallized slowly. The solid was filtered off, washed with
water, and dried in a desiccator over silica gel to give 7.4 g of
1,3-dinitropyrazole.
The latter was suspended in 50 mL of o-dichlorobenzene, and
the suspension was heated to the boiling point of the solvent.
This caused the starting material to dissolve with a noticeable
evolution of nitrogen oxides. After 3 h, the reaction mixture was
cooled to room temperature and the precipitate formed was
filtered off and dried to give a mixture (6.3 g) of 3-nitro (15–20%)
and 3,5-dinitropyrazole (80–85%).
This mixture (2.2 g) was dissolved in 20mL of ethyl acetate and
extracted with 30mL of 3–5% aqueous solution of NaHCO3. The
aqueous phase was concentrated to 10–15 mL and acidified to
pH 1–2 with concentrated HCl. The precipitated 3,5-dinitropyrazole
was filtered off, washed with a minimum amount of ice water,
and dried. The yield of the pure product varied from 0.9 (41%)
to 1.3 g (60%). Tm 172 ꢀC (lit. [7] 173–174 ꢀC) 1H NMR
(DMSO-d6) 7.94 (1H, s).
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3,5-Dinitro-4-aminopyrazole (1) from 3,5-dinitropyrazole
compound. However, the product of its deprotection in 60%
H2SO4 had the same spectral characteristics as described for
4-amino-3,5-dinitropyrazole, vide infra.
(4).
3,5-Dinitropyrazole (1.0 g, 6.3 mmol) and 4-amino-1,2,
4-triazole (0.58 g, 6.9 mmol) were dissolved in DMSO (12 mL)
and then t-BuOK (1.7 g, 15.1 mmol) was added in one portion. The
reaction mixture turned crimson red and was stirred at ambient
temperature for 3 h before being poured onto ice (33 g). The pH of
the brown-red milky solution was adjusted to 3 with 10% HCl.
The resulting yellow precipitate was filtered off to yield the DMSO
solvate of the desired compound (1.3 g, 5.2 mmol, 82.5%).
3,5-Dicarboxy-4-ethylcarbethoxyaminopyrazole (12). The
same procedure was used as in the synthesis of
4-ethoxycarbonylamino-1-ethoxycarbonylpyrazole, vide supra. In
this case, 3,5-dicarboxy-4-nitropyrazole[18] was used as the
1
starting material. Yield 72% of an off-white powder. H NMR
(DMSO-d6) 8.56 (1H, s), 4.01 (2H, J = 7.0 Hz, q), 1.17 (3H,
J = 7.0Hz, t). 13C NMR (DMSO-d6) 162.8, 154.5, 139.0, 122.8,
60.8, 14.9. Satisfactory elemental analysis could not be obtained
for this compound. However, the product of its deprotection in
60% H2SO4 had the same spectral characteristics as described for
4-amino-3,5-dinitropyrazole, vide infra.
1
Tm 160 ꢀC (lit. [6] 160–162 ꢀC) H-NMR (DMSO-d6) d 7.1 (3H,
brs, NH2 and NH). 13C-NMR (DMSO- d6) d 137.8, 128.8.
4-Nitropyrazole (2).
Pyrazole (14 g, 0.206 mmol, 1 equiv)
was dissolved in concentrated H2SO4 (50 mL). The solution was
heated to 60 ꢀC, before the dropwise addition of nitric acid (9.2 mL,
0.226 mL, 100%, 1.1 equiv), which caused the temperature rise
slightly. The reaction was stirred for 1½ h at 60 ꢀC. The solution
was poured into 600 g of an ice/water mixture. A white precipitate
formed and was filtered off, washed with water and dried. This
yielded 12.5 g (54%). The mother liquor was extracted with ethyl
acetate (3 Â 100 mL). The combined organic phases were washed
with 1% NaHCO3 (aq, 100 mL), water (100 mL), and brine
(100 mL). The ethyl acetate solution was dried over Na2SO4 and
concentrated in vacuo, which yielded another 10.5 g (45%) of the
desired product. 155 ꢀC (Lit. [22] 150–160 ꢀC) 1H NMR (DMSO-d6)
12.91 (1H, bs), 8.56 (2H, s), 13C NMR (DMSO-d6) 135.4, 132.2
3,5-Dinitro-4-aminopyrazole (1) from 4-ethylcarbethoxyamino-
3,5-dinitropyrazole (9). 4-Ethylcarbethoxyamino-3,5-dinitropyrazole
(1g, 4.1 mmol) was suspended in H2SO4 (60% w/w, aq) and stirred
overnight at 100ꢀC. Brownish yellow crystals precipitated upon
cooling of the solution to room. This product was filtered off and
dissolved in boiling water. Adjustment of the pH to 1 with
hydrochloric acid resulted in precipitation of 0.78g (70%) of
yellow crystals. The crystals were dissolved in EtOAC (20 mL).
Toluene (200mL) was added to the solution. The resulting
solution was concentrated in vacuo to dryness. The yield was
0.71g (100% from the hydrate) of bright yellow, fine crystals of
1. Tm = 176ꢀC (lit.[6] 175–178 ꢀC) 1H NMR (DMSO-d6) 7.14
(2H, s), 13C NMR (DMSO-d6) 131.75, 128.4
4-Ethylcarbethoxyamino-1-ethylcarbethoxypyrazole (8).
Potassium hydroxide (19.8 g, 85%) was dissolved in 150 mL
H2O. 4-Nitropyrazole (6 g, 53.04 mmol, 1 equiv) was added,
thus producing a yellowish solution. Sodium dithionite (43.2g,
0.212 mol, 85%, 4 equiv) was added in three portions. Much
heat was released during the addition and the color changed
in tones of orange and green. The resulting mixture was
refluxed for 1 h (120–125 ꢀC) and was then left to cool to
ambient temperature. Ethyl chloroformate (12.8 mL, 0.133 mol,
2.5 equiv) was added in one portion. Precipitation of the product
started almost immediately, but the flask was left overnight not
to interrupt the precipitation prematurely. The product was
filtered off, washed with water, and dried at 40 ꢀC. This
procedure resulted in 5.42 g (45%) white powder. Tm = 177 ꢀC
(lit. 175–178 ꢀC [6]) 1H NMR (DMSO-d6) 9.81 (1H, s), 8.09
(1H, s), 7.73 (1H, s), 4.39 (2H, J = 7.2 Hz, q), 4.29 (2H,
J = 6.8 Hz, q), 1.34 (3H, J = 6.8 Hz, t), 1.23 (3H, J = 6.8 Hz, t).
13C NMR (DMSO-d6) 153.94, 149.17, 141.13, 125.44, 64.56,
61.20, 15.05, 14.45. Satisfactory elemental analysis could not
be obtained for this compound. However, the product of its
nitration in mixed acids, followed by deprotection in 60%
H2SO4 had the same spectral characteristics as described for
4-amino-3,5-dinitropyrazole, vide infra.
4-Chloropyrazole (5).
Hydrochloric acid (16 mL, 35%,
0.52 mol) was diluted with 100 g ice water. Pyrazole (6.95 g,
98%, 0.1 mol) was dissolved in the dilute acid. Sodium
hypochlorite (85 mL, 14%, 0.2 mol) was slowly added under
vigorous stirring to the solution with the temperature kept below
5 ꢀC. After 18 h at ambient temperature, the solution was
neutralized with sodium hydroxide. A white precipitate formed
and also some darker solids. The precipitate was filtered and
washed with water. The white solid dissolved and the residual
filter cake was grayish brown. The filtrate was extracted with
3 Â 100 mL diethyl ether, which was dried and concentrated in
vacuo, but not until dryness to avoid losses due to sublimation.
To remove the all traces of ether, air was bubbled through
the solution at ambient temperature and pressure. The sticky
product was transferred to
a sublimation apparatus. The
sublimation provided 8.37 g (81%) white, sticky crystals.
1
Tm =75ꢀC (lit.[23] 75–76 ꢀC) H NMR (DMSO-d6) 13.12 (1H, s),
7.76 (2H, J = 152.4 Hz, d), 13C NMR (DMSO-d6) 108.45, 104.68
Calcd. C 35.15%, H 2.95%, Cl 34.58%, N 27.32%. Found C
35.22%, H 3.05%, Cl 34.43%, N 27.24%.
4-Chloro-3,5-dinitropyrazole (13).
4-chloropyrazole (7.4 g,
4-Ethylcarbethoxyamino-3,5-dinitropyrazole (9).
4-Ethyl-
0.072 mol) was added to oleum (15 mL, 20%) under cooling in
such a rate that the temperature was kept below 25 ꢀC. The
solution was heated to 60ꢀC. A mixture of HNO3 (18 mL) and
oleum (20 mL, 65%) was prepared under cooling. A third of that
mixture was slowly added to the acid solution of 4-
chloropyrazole. The temperature was maintained between 65
and 70 ꢀC throughout the addition. The temperature was then
raised to 85 ꢀC. The remaining nitration mixture was slowly
added with the temperature kept below 95 ꢀC. After 45 min at
this temperature, the flask left in the bath to slowly
cool. The product precipitated and was filtered off and washed
with 8–10mL concentrated sulfuric acid. The filter cake was
suspended in 40–50mL ice water to provide a thick broth. This
carbethoxyamino-1-ethylcarbethoxypyrazole (0.5 g, 2.2 mmol) was
suspended in concentrated sulfuric acid (5mL). A total of 100%
nitric acid (0.20mL, 4.81mmol, 2.2 equiv) was added. The
solution turned yellow-red upon the addition and gas evolved.
After 1 h at ambient temperature, the solution was poured onto ice
(25 g). The aqueous phase was extracted with 3 Â 50 mL Et2O. The
combined organic phases were dried over Na2SO4 and
concentrated in vacuo, thus yielding 0.52 g (95%) of a yellow
1
oily to semisolid product. H NMR (DMSO-d6) 9.85 (1H, s),
4.12 (2H, J = 6.8 Hz, q), 1.21 (3H, J = 7.2 Hz, t). 13C NMR
(DMSO-d6) 153.34, 140.68, 112.31, 31.54, 14.83. No
satisfactory elemental analysis could be obtained for this
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Four Syntheses of 4-Amino-3,5-dinitropyrazole
was filtered to isolate the product, which was washed with
15 mL cold water and dried. This procedure yielded 9.0 g
(57%) of a white, solid product (13). Tm = 158–160 ꢀC. 1H
NMR (DMSO-d6) no peaks, 13C NMR (DMSO-d6) 152.67,
108.46. Calcd. (4-Cl-3,5-DNP) C 18.72%, H 0.52%, Cl
18.42%, N 29.10%. Found C 16.91%, H 1.30%, Cl 16.63%, N
25.69%. Calcd. (4-Cl-3,5-DNP•1½ H2O) C 16.41%, H 1.15%,
Cl 16.15%, N 25.52%.
The diluted nitration mixture and the washing acid and waters
were combined and extracted with 3 Â 100 mL EtOAc. Drying
and concentration of the combined organic phases produced
another 5.7 g (36%) of off-white product 13, which had the same
NMR characteristics as mentioned earlier.
Liu, G.; Liashenko, A.; Piskorz, I. K. P.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, C. Y. P. M. A.; Nanayakkara, A.; Gon-
zalez, C.; Challacombe, M.; Gill, B. J. P. M. W.; Chen, W.; Wong, M.
W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, E. S. R. M.; Pople, J.
A., In Gaussian, Gaussian Inc.: Pittsburgh, PA, 1998.
[2] Jacob, G.; Bénazet, S.; Tryman, R.; Goede, P.; Östmark, H.
Calculation of densities and heats of formations of energetic molecules
for the use in thermochemical codes, New Trends in Research of
Energetic Materials, VIII Seminar, Pardubice, Czech Republic, April
19–21 2005, Vol. 1, p 222.
[3] Latypov, N. V.; Bergman, J.; Langlet, A.; Wellmar, U.;
Bemm, U. Tetrahedron 1998, 54, 11525.
[4] Vinogradov, V. M.; Cherkasova, T. I.; Dalinger, I. L.; Shevelev,
S. A. Russ Chem Bull Int Ed 1993, 42, 1552.
[5] Shevelev, S. A.; Dalinger, I. L. Russ J Org Chem 1998,
34, 1071.
[6] Schmidt, R. D.; Lee, G. S.; Pagoria, P. F.; Mitchell, A. R.;
Gilardi, R. J Heterocycl Chem 2001, 38, 1227.
4-Amino-3,5-dinitropyrazole (1) from 4-chloro-3,5-
dinitropyrazole (13).
4-Chloro-3,5-dinitropyrazole (8 g) was
suspended in concentrated aqueous ammonia (26 mL, 28%) in a
Teflon microwave reactor. The vessel was sealed and inserted
into the microwave oven. It was heated under stirring to 130 ꢀC
for 6 h. The color had changed from off-white to yellow.
The contents of the vessel was transferred to a flask and
concentrated in vacuo. The orange product was dissolved in a
minimum amount of boiling water. The pH of the solution was
adjusted to 1 with hydrochloric acid. The hydrate of the desired
product separated on cooling. The product was filtered off and
dried overnight at 40 ꢀC. It was dissolved in EtOAC (100 mL).
Toluene (100 mL) was added to the solution. The resulting
solution was concentrated in vacuo to dryness. The yield was
4.8 g (73%) of bright yellow, fine crystals of anhydrous 1.
Tm = 177 ꢀC (lit.[6] 175–178 ꢀC) 1H NMR (DMSO-d6) 7.14
(2H, s), 13C NMR (DMSO-d6) 131.75, 128.4 Calcd. C 20.82%,
H 1.75%, N 40.46%. Found C 21.05%, H 1.84%, N 40.28%.
[7] Janssen, J. W. A. M.; Koeners, H. J.; Kruse, C. G.; Habraken,
C. L. J Org Chem 1973, 38, 1777.
[8] Hervé, G.; Roussel, C.; Graindorge, H. Angew Chemie Int Ed
2010, 49(18), 3177.
[9] Dalinger, I. L.; Vatsadze, I. A.; Shkineva, T. K.; Popova, G. P.;
Shevelev, S. A., Mendeleev Commun 2010, 20, 253–254.
[10] Janssen, J. W. A. M.; Habraken, C. L. J Org Chem 1971,
36, 3081.
[11] Redemann, C. T.; Redemann, C. E. Org Synth CV 3, 69, 1955.
[12] Curry, H. M.; Mason, J. P. J Am Chem Soc 1951, 73, 5043.
[13] Gorton, B. S.; Shive, W. J Am Chem Soc 1957, 79, 670.
[14] Raucher, S.; Bray, B. L.; Lawrence, R. F. J Am Chem Soc
1987, 109, 442.
[15] Shono, T.; Matsumura, Y.; Uchida, K.; Tsubata, K.; Makino,
A. J Org Chem 1984, 49, 300.
[16] Wani, M. C.; Campbell, H. F.; Brine, G. A.; Kepler, J. A.;
Wall, M. E. J Am Chem Soc 1972, 94, 3631.
[17] Wenkert, E.; Hudlický, T.; Hollis Showalter, H. D. J Am
Chem Soc 1978, 100, 4893.
[18] Musante, L., Gazz Chim Ital 1942, 73, 537.
[19] Coburn, M. D. J Heterocycl Chem 1971, 8, 153.
[20] Hüttel, R.; Büchele, F. Chem Ber 1955, 88, 1586.
[21] Perevalov, V. P.; Manaev, Y. A.; Baryshnenkova, L. I.;
Kanep, E. E.; Andreeva, M. A.; Stepanov, B. I. Chem Heterocycl Comp
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet