Hydrogen halides as nucleophilic agents for 3,4,5-trinitro-1H-pyrazoles

Article abstract of DOI:10.1016/j.mencom.2012.01.017

1-R-3,4,5-Trinitropyrazoles (R = H, Me) undergo nucleophilic substitution on treatment with concentrated hydrogen halide solutions to give 5-halo-1-R-3,4-dinitropyrazoles.

Full text of DOI:10.1016/j.mencom.2012.01.017

Mendeleev
Communications
Mendeleev Commun., 2012, 22, 43–44
Hydrogen halides as nucleophilic agents for 3,4,5-trinitro-1H-pyrazoles
Igor L. Dalinger,* Irina A. Vatsadze, Tatyana K. Shkineva,
Galina P. Popova and Svyatoslav A. Shevelev
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: dalinger@ioc.ac.ru
DOI: 10.1016/j.mencom.2012.01.017
1-R-3,4,5-Trinitropyrazoles (R = H, Me) undergo nucleophilic substitution on treatment with concentrated hydrogen halide solutions
to give 5-halo-1-R-3,4-dinitropyrazoles.
NO2
NO2
An increasing interest in pyrazoles is due to the fact that they can
find use for peaceful1 and military purposes.2 Previously, we have
shown that replacement of NO2 group in 3,4- and 3,5-dinitropyr-
azoles is a versatile approach to molecules containing C(pyrazole)–
X(O,S,N) bonds.3 This reaction pathway is characteristic of
dinitropyrazoles containing no additional groups capable of nucleo-
philic substitution. In 3,4-dinitropyrazoles, irrespective of the
capability to undergo ionization under the reaction conditions,
i.e. in the presence or absence of a substituent at the N1 ring
atom, only the 3-NO2 group is selectively replaced on treatment
with nucleophiles. On the other hand, N1-substituted 3,5-dinitro-
pyrazoles react with nucleophiles with selective replacement
of the 5-NO2 group, whereas in the case of N1-unsubstituted
analogues the reaction stalls in salt formation due to ionization
of the N(ring)–H bond.
O2N
NO2
O2N
Hal
N
N
N
N
R
R
1 R = H
2 R = Me
3 R = H, Hal = Cl
4 R = H, Hal = Br
5 R = Me, Hal = Cl
6 R = Me, Hal = Br
Scheme 1 Reagents and conditions: HCl (35%) or HBr (48%), 60–70°C.
pyrazole.9 Additional proof of the structures of compounds 3
and 4 was obtained by comparison of their 13C NMR chemical
shifts with those in 3,5-dinitro-4-chloropyrazole 7,‡ i.e. 103 and
150 ppm.
Recent studies carried out by our group4,5 as well as those
by Herve et al.6 provided 3,4,5-trinitro-1H-pyrazole 1 and its
N-methyl derivative, namely, 1-methyl-3,4,5-trinitro-1H-pyrazole
2, the first representatives of pyrazoles completely nitrated at the
carbon atoms.
We have found that the features of nucleophilic substitution in
polynitropyrazoles of this type differ from the previously known
behaviour. With O-, S-, N-anionic (RX–, X = O, S, N) and
covalent N-nucleophiles, trinitropyrazole 1 reacts in anionic
form due to the high NH-acidity of compound 1 (pKa = 0.05,5
pKa = 2.356). This involves reactivity reversal, and it is the 4-NO2
group that undergoes selective nucleophilic substitution.5,7 On
the other hand, the nucleophilic substitution in N1-substituted
compound 2, conforms to the general regularities for 3,4- and
3,5-dinitropyrazoles described above, i.e., the 3(5)-nitro group is
replaced.8
To confirm our viewpoint that the regiospecificity of nucleo-
philic substitution in the trinitropyrazole series is primarily
governed by their ionisation capability, we studied the reac-
tion of compounds 1 and 2 with hydrogen halides. Note that
trinitropyrazole 1 is not ionised in concentrated hydrogen halide
solutions.
In fact, heating of trinitropyrazole 1 at 60–70°C in con-
centrated aqueous HCl and HBr solutions gives compounds 3
and 4; complete conversion is reached within 15 h and the yields
are 90 and 60%, respectively (Scheme 1).† 13C NMR data showed
that these compounds are 5-chloro-3,4-dinitropyrazole 3 and
5-bromo-3,4-dinitropyrazole 4, respectively, since they contained
three signals at 116–118, 125–127 and 150 ppm, which corre-
spond to three different carbon atoms of unsymmetric structures,
two of these signals are broadened (C–NO2). Furthermore, these
spectra were identical to those of the specimens of compounds
3 and 4 that we obtained previously from 5-diazo-3,4-dinitro-
N-Methyl-substituted trinitropyrazole 2 reacts with aqueous
hydrogen halides in a similar manner and faster than compound
1: the complete conversion is attained within 5 h of heating at
60–70°C. The reaction gives 5-chloro-1-methyl-3,4-dinitropyrazole
5 and 5-bromo-1-methyl-3,4-dinitropyrazole 6 in 90% and 80%
yields, respectively (Scheme 1).§
The structures of these compounds were established based
on the differences in the NMR spectral characteristics of 5 and 6
†
The structures of all the compounds were determined using 1H and
13C NMR spectroscopy in [2H6]DMSO (Bruker AC-300) and confirmed
by IR (Bruker ALPHA) and mass (Finnigan MAT Incos 50) spectra as
well as by elemental analyses. All the compounds have absorption bands
at 1325 and 1520 cm–1 (NO2) in the IR spectra and a molecular ion peak
[M]+ in the mass spectra.
5-Halo-3,4-dinitropyrazoles (general procedure). A solution of 2 mmol
trinitropyrazole 1 in 4 ml conc. HCl (d = 1.175 g cm–3) or HBr (d =
= 1.48 g cm–3) was heated for 15 h at 60–70°C with stirring. The mixture
was diluted with H2O (15 ml) and extracted with diethyl ether (3×5 ml);
the organic layer was dried with Na2SO4. The solvent was removed in vacuo
and the residue was crystallized from CCl4.
5-Chloro-3,4-dinitro-1H-pyrazole 3: yield 95%, mp 110–111°C (lit.,9
mp 110–112°C). 13C NMR, d: 148.63 (C3), 130.68 (C5), 122.69 (C4).
5-Bromo-3,4-dinitro-1H-pyrazole 4: yield 63%, mp 120–121°C (lit.,9
mp 118–120°C). 13C NMR, d: 149.97 (C3), 125.38 (C4), 117.76 (C5).
‡
4-Chloro-3,5-dinitropyrazole was first mentioned in our study,10 but we
did not provide experimental details of its synthesis at that time.
4-Chloro-3,5-dinitro-1H-pyrazole 7. Nitric acid (20 ml, d = 1.51 g cm–3)
was added dropwise with stirring to a solution of 4-chloropyrazole (15.6 g,
0.12 mol) in H2SO4 (190 ml, d = 1.824 g cm–3) at 15–25°C. The reaction
mixture was kept for 5 h with stirring at 100–105°C, poured into 1 liter
of ice water and extracted with ethyl acetate (2×300 ml). The organic
layer was washed with water and dried with MgSO4; the solvent was
removed in vacuo and the residue was crystallized from water to give
16.9 g (70%) of compound 7. Mp 157–159°C. 13C NMR, d: 148.97 (C3,5),
103.09 (C4).
© 2012 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2012, 22, 43–44
the N1 ring atom and obeys the rule of selective substitution at
Cl
Cl
Br
positions 3 or 5 that is common to 3,4- and 3,5-dinitropyrazoles.
This confirms our supposition that regiodirection of nucleo-
philic substitution in 3,4,5-trinitropyrazoles is determined by
whether they are N–H ionized or not.
O2N
NO2
O2N
NO2 O2N
NO2
N
NH
N
N
N N
Me
Me
7
8
9
References
from those of known 4-chloro-1-methyl-3,5-dinitropyrazole 8¶
and 4-bromo-1-methyl-3,5-dinitropyrazole 9.12 A typical distinc-
tion consists in the upfield shifts of the 1H (4.02; 3.95 ppm) and
13C NMR signals corresponding to the methyl group of compounds
5 and 6 in comparison with similar shifts (4.25 and 4.33 ppm)
in compounds 8 and 9. Additionally, compound 5 was studied
by 2D HMBC NMR experiment, which displayed correlation
between NMe protons and carbon atom at 130.6 ppm. Since this
signal had no quadrupole broadening typical of nitrogen action,
it was assigned to C–Cl.
1 A. Schmidt and A. Dreger, Curr. Org. Chem., 2011, 15, 1423.
2 (a) J. P. Agrawal and D. L. Hodgson, Organic Chemistry of Explosives,
John Wiley & Sons, Chichester, 2007, pp. 332–334; (b) High Energy
Density Materials, ed. T. M. Klapötke, in Series Structure and Bonding,
ed. D. M. P. Mingos, Springer, 2007, vol. 125, pp. 123–151.
3 (a) A. A. Zaitsev, I. L. Dalinger and S. A. Shevelev, Usp. Khim., 2009, 78,
643 (Russ. Chem. Rev., 2009, 78, 589); (b) I. L. Dalinger, I. A. Vatsadze,
T. K. Shkineva, I. O. Kortusov, G. P. Popova, V. V. Kachala and S. A.
Shevelev, Izv. Akad. Nauk, Ser. Khim., 2010, 1739 (Russ. Chem. Bull.,
Int. Ed., 2010, 59, 1786).
4 I. L. Dalinger, G. P. Popova, I. A. Vatsadze, T. K. Shkineva and S. A.
Shevelev, Izv. Akad. Nauk, Ser. Khim., 2009, 2120 (Russ. Chem. Bull.,
Int. Ed., 2009, 58, 2185).
5 I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova and S. A.
Shevelev, Mendeleev Commun., 2010, 20, 253.
In summary, the regiospecificity of nucleophilic substitution
in trinitropyrazole derivatives on treatment with hydrogen halides
does not depend on the presence or absence of a substituent at
6 G. Herve, C. Roussel and H. Graindorge, Angew. Chem. Int. Ed., 2010,
49, 3177.
7 I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova and S. A.
Shevelev, Mendeleev Commun., 2010, 20, 355.
8 I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova and S. A.
Shevelev, Mendeleev Commun., 2011, 21, 149.
9 I. L. Dalinger, I. A. Vatsadze, T. K. Shkineva, G. P. Popova, B. I. Ugrak
and S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2010, 1589 (Russ. Chem.
Bull., Int. Ed., 2010, 59, 1631).
§
5-Halo-1-methyl-3,4-dinitropyrazoles (general procedure). Aqueous HCl
(4 ml, d = 1.175 g cm–3) or HBr (4 ml, d = 1.48 g cm–3) were added to a
solution of compound 2 (2.62 mmol) in MeOH (4 ml); the reaction
mixtures were heated for 5 h at 60–70°C with stirring. The solvent was
removed in vacuo and the residue was crystallized from CCl4.
5-Chloro-1-methyl-3,4-dinitro-1H-pyrazole 5: yield 89%, mp 59–61°C.
1H NMR, d: 4.02 (s, 3H, Me). 13C NMR, d: 146.59 (C3), 130.61 (C5),
123.20 (C4), 38.47 (NMe).
10 V. M. Vinogradov, I. L. Dalinger and S. A. Shevelev, Mendeleev Commun.,
5-Bromo-1-methyl-3,4-dinitro-1H-pyrazole 6: yield 79%, mp 53–55°C.
1H NMR, d: 3.95 (s, 3H, Me). 13C NMR, d: 147.20 (C3), 125.32 (C4),
119.76 (C5), 39.38 (NMe).
1993, 111.
11 V. P. Manaev, M. A. Andreeva, V. P. Perevalov, B. I. Stepanov, V. A.
Dubrovskaya and V. I. Seraya, Zh. Obshch. Khim., 1982, 52, 2592 [J. Gen.
Chem. USSR (Engl. Transl.), 1982, 52, 2291].
¶
4-Chloro-1-methyl-3,5-dinitro-1H-pyrazole 8. Compound 7 (0.58 g,
3 mmol) was added to a solution of NaHCO3 (0.51 g, 6 mmol) in H2O
(10 ml). The reaction mixture was stirred for 10 min, then Me2SO4
(0.34 ml, 3.6 mmol) was added. The mixture was stirred for 4 h at room
temperature. The precipitate formed was filtered off and dried with
P2O5 to give 0.54 g (87%) of compound 8. Mp 101–103°C (lit.,11
mp 101.5–102.5°C). 1H NMR, d: 4.25 (s, 3H, Me). 13C NMR, d: 148.10
(C3), 143.15 (C5), 105.92 (C4), 43.83 (NMe).
12 M. D. Coburn, J. Heterocycl. Chem., 1971, 8, 153.
Received: 11th July 2011; Com. 11/3759
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