Synthesis and characterization of some n-aryl-4-nitroimidazoles as potential insensitive energy materials

Article abstract of DOI:10.1002/cjoc.201201001

N-Aryl derivatives of 4-nitroimidazole have been synthesized under CuI/TBAB catalytic system in excellent yields, using KOH as base in DMF solvent. N-Aryl derivatives of 4-nitroimidazole have been synthesized under CuI/TBAB catalytic system in excellent y

Full text of DOI:10.1002/cjoc.201201001

FULL PAPER
DOI: 10.1002/cjoc.201201001
Synthesis and Characterization of Some N-Aryl-4-nitroimid-
azoles as Potential Insensitive Energy Materials
Kehui Hou and Zuliang Liu*
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
N-Aryl derivatives of 4-nitroimidazole have been synthesized under CuI/TBAB catalytic system in excellent
yields, using KOH as base in DMF solvent.
Keywords organic chemistry, synthesis, CuI-catalyzed, N-arylation, 4-nitroimidazole
Introduction
tocols for the experimentally simple transition metal-
catalyzed N-arylation of free (NH)-imidazoles with aryl
The synthesis and development of new, insensitive
energetic materials that contain aromatic nitrogen-con-
taining heterocyclic core units have attracted attention
due to their more favorable elemental composition with
relatively higher energetic performance in regard to
oxygen balance, density, and other thermodynamic
properties when compared to their carbon-only analo-
gous aromatic compounds.[1-7] It is with this background
and in continuation of our program aimed at synthesis
of new nitroimidazole-based energetic materials that we
have undertaken the synthesis of N-aryl-C-nitroimid-
azoles.
Scheme 1 Synthesis scheme of N-aryl-4-nitroimidazoles
Route 1:
R2
NO2
R1
N
MeOH: H2O
H2N
R2
+
N
O2N
R1 = H, CH3
R1
N
25 ℃, 24 h
R2 = Br, OCH3, Cl
N
O2N
It has been reported in the literature[8] that when
1,4-dinitroimidazole reacted with anilines in aqueous
methanol at ambient temperature, degenerated ring
transformation occurred, thereby providing 1-aryl-4-
nitroimidazoles, in high yields, containing electron-do-
nating or relatively weak electron-withdrawing sub-
stituents like OH, OR, R, Cl, Br, COOR etc. in aryl
group. Very weak nucleophiles (e.g. 2,4-dinitroaniline)
do not react with 1,4-dinitroimidazole (Scheme 1, Route
1). In order to introduce 2,4-dinitrophenyl substituent on
the pyrrole type nitrogen atom in C-nitro-1H-azoles,
Searcey and co-workers[9] utilized tetraalkyl ammonium
salts of nitroimidazoles to react with halo compounds.
Walczak and co-workers[8] used a reaction of 1-fluoro-
2,4-dinitro- or 1-fluoro-4-nitrobenzene accordingly with
nitroazole-1,8-diaza-bicycle[5.4.0]-7-undecenium salts
(Scheme 1, Route 2). Dissolution of 4-nitroimidazole
(4-NI) in DMF and treatment with picryl fluoride at
ambient temperature, followed by quenching in water,
afforded 4-nitro-1-picrylimidazole in 68% yield.[10] All
of these either used active fluoride compounds as sub-
strate or had a low yield, chloride compounds are little
reported. In the past few years, a wide number of pro-
Route 2:
H
THF
R1
N
N
+
, 2 h
25 ℃
N
R1 = H, CH3
N
O2N
NO2
, DMF
25 ℃
R2
R1
O2N
F
N
R2
N
O2N
R2 = H, NO2
This work:
O2N
O2N
N
Cl
O2N
NO2
NH2
N
N
CuI/TBAB
KOH
O2N
NO2
NH2
+
N
H
NO2
DMF, 25 ℃
NO2
yields up to 98%
*
E-mail: liuzl@mail.njust.edu.cn; Tel.: 0086-025-84318865; Fax: 0086-025-84315030
Received October 14, 2012; accepted December 6, 2012; published online January 8, 2013.
Supperting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201201001 or from the author.
Chin. J. Chem. 2013, 31, 243—246
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243

Hou & Liu
FULL PAPER
halides has been described,[11,12] but nitroimidazoles are
little reported. Nitroimidazoles have been used as anti-
fungal, antibacterial, antiviral, antitumor drugs and their
intermediates[8,13] and recently as high energy materials,
respectively.
In this work, we utilize chloronitroarenes to react
with 4-nitroimidazoles under the catalytic system CuI/
TBAB, which gives N-aryl-4-nitroimidazoles in excel-
lent yields. This is a new and practical route to synthesis
of nitroimidazole-based energetic materials.
Experimental
A general procedure for the preparation of N-aryl-
4-nitroimidazoles
A mixture of 4-nitroimidazole (1a 0.45 g, 4 mmol),
KOH (0.22 g, 4 mmol) and DMF (15 mL) was stirred at
ambient temperature for 1 h, followed by CuI/TBAB
(0.03 g/0.06 g, 0.16 mmol/0.19 mmol), then chloroni-
troarene (1b, 2b, 3b, 4b, 5b, 4 mmol) was added in
small lots with stirring. The contents were kept stirring
for 2－4 h at room temperature. The reaction mixture
was poured onto ice-water mixture. The precipitations
were collected and dried on air, recrystallized from ace-
tone/methol, giving 1c－5c, respectively.
Figure 1 ORTEP view of 3c.
3,5-Di-(4'-nitroimidazole)-2,4,6-trinitro-benzenamine
(5c)
Yield: 75%; m.p. 235－238 ℃; 1H NMR (500 MHz,
DMSO-d6) δ: 8.85 (s, 1H), 8.78 (s, 1H), 8.54 (s, 2H),
8.27 (s, 1H), 8.22 (s, 1H); 13C NMR (125 MHz,
DMSO-d6) δ: 121.51, 123.16, 126.30, 130.83, 134.87,
137.34, 139.04, 169.84. Anal. calcd for C12H6N10O10: C
32.01, H 1.34, N 31.11; found C 31.96, H 1.31, N 31.12.
MS (ESI) m/z: 448.82 (M−H).
1-(2',4'-Dinitrophenyl)-4-nitroimidazole (1c)
Yield: 80%; m.p. 150－152 ℃ (153－154 ℃[8]);
1H NMR (500 MHz, DMSO-d6) δ: 9.01 (d, J＝2.5 Hz,
1H), 8.91 (d, J＝1.15 Hz, 1H), 8.79 (dd, J＝2.5, 8.7 Hz,
1H), 8.30 (d, J＝1.15 Hz, 1H), 8.19 (d, J＝8.7 Hz, 1H).
Results and Discussion
4-NI reacted with 1-chloro-2,4-dinitrobenzene (1b)
in DMF using pyridine as base, no reaction occurred at
room temperature. Rising the temperature (80 ℃), we
just obtained hydrolysis product. However, hydrolysis
occurred when 4-NI reacted with picryl chloride (2b) at
room temperature. Using inorganic base such as K2CO3
and KOH, the results were unchanged. Fortunately, we
got 3c in moderate yield (65%) when 4-NI reacted with
3b in DMF under KOH condition, comparing to the
virtually quantitative yield (98%) when under CuI/
TBAB catalysis, which can actually avoid the self-reac-
tion of 3b (Table 1).
1-(2',4',6'-Trinitrophenyl)-4-nitroimidazole (2c)
Yield: 83%; m.p. 280－282 ℃ (286－287 ℃[10]);
1H NMR (500 MHz, DMSO-d6) δ: 9.37 (s, 2H), 8.86 (d,
J＝1.45 Hz, 1H), 8.29 (d, J＝1.45 Hz, 1H).
1-(3'-Amino-2',4',6'-trinitrophenyl)-4-nitro-imidaz-
ole (3c)
Yield: 98%; m.p. 246－248 ℃; 1H NMR (500 MHz,
DMSO-d6) δ: 9.12 (s, 1H), 8.76 (d, J＝1.3 Hz, 1H), 8.75
(s, 2H), 8.18 (d, J＝1.3 Hz, 1H); 13C NMR (125 MHz,
DMSO-d6) δ: 122.63, 126.33, 127.96, 129.63, 137.93,
147.31. MS (ESI) m/z: 337.86 (M−H). Structure of this
product was established unambiguously via single crys-
tal X-ray crystallography (Figure 1). Selected X-ray
data:[14] crystal system, monoclinic; space group, P21/N;
volume, 1302.1 A3; Z, 4; density, 1.73 g/cm3.
Table 1 The results under different conditionsa
Substrate Procedure modification
Yieldb/%
Without CuI/TBAB, reaction at r.t. No reaction or
1b
or 80 ℃ using pyridine as base
Hydrolysis
80
Under CuI/TBAB, reaction at r.t.
2b
3b
Without CuI/TBAB, reaction at r.t. Hydrolysis
Under CuI/TBAB, reaction at r.t. 83
Without CuI/TBAB, reaction at r.t. 65
Under CuI/TBAB, reaction at r.t. 98
1-(3',5'-Diamino-2',4',6'-trinitrophenyl)-4-nitro-imid-
azole (4c)
Yield: 83%; m.p. 296－298 ℃; 1H NMR (500 MHz,
DMSO-d6) δ: 8.77 (d, J＝1.3 Hz, 1H), 8.18 (d, J＝1.3
13
a All reactions carried out using KOH as base unless otherwise
stated; b Isolated yield.
Hz, 1H), 8.21 (s, 4H); C NMR (125 MHz, DMSO-d6)
δ: 121.09, 121.69, 123.26, 129.29, 137.03, 138.81,
141.21, 146.24, 147.23. Anal. calcd for C9H6N8O8: C
30.52, H 1.71, N 31.64; found C 30.48, H 1.76, N 31.62.
MS (ESI) m/z: 352.86 (M−H).
4-NI and 3-chloro-2,4,6-trinitro-benzenamine (3b)
were used as model substrates to optimize the reaction
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Chin. J. Chem. 2013, 31, 243—246

Synthesis and Characterization of Some N-Aryl-4-nitroimidazoles as Energy Materials
conditions. Effects of parameters such as catalyst, base,
and additive were studied (Table 2). In our initial
experiment, 3b (1 equiv.) was treated with 4-NI (1
equiv.) in DMF at room temperature for 2 h in the
presence of KOH (1 equiv.); only moderate yield of 3c
was obtained (Table 2, Entry 1). Adding TBAB to the
reaction led to only a slight increase of yield (Table 2,
Entry 2), but a good yield was obtained in the presence
of CuI (Table 2, Entry 3). It was found that CuI/TBAB
catalyst with KOH afforded an excellent yield (98%)
whereas K2CO3 gave moderate yields (69%) and
KHCO3 showed equal activity as NaOH (84% and 80%,
respectively) (Table 2, Entries 4, 7－9). Other copper
compounds (CuO and Cu(OAc)2) were also evaluated
but proved inferior to CuI (Table 2, Entries 5 and 6).
Scheme 2 The possible catalytic cycle driven by CuI
As described in Scheme 2, we have formulated a
possible catalytic cycle for the copper catalyzed
N-arylation of nitro-imidazole based on the previously
reported mechanism.[11] There are two ways to lead to
the intermediate (II) which undergoes a reductive
elimination to provide the target product and to regener-
ate the Cu(I). First way described as A: Chelation of Cu(I)
with potassium salt of 4-NI occurs to form the (I) and
the subsequent oxidative addition of the (I) with aryl
chloride leads to the intermediate (II); Another way
described as B: Oxidative addition of Cu(I) with aryl
chloride leads to the Cu(III), then chelation of it with po-
tassium salt of 4-NI occurs to form the intermediate (II).
To confirm the possible catalytic cycle, we designed the
following reactions (Table 4).
Table 2 Optimization of conditions for the synthesis of
N-aryl-C-nitroimidazolesa
Entry Catalyst
Additive
－
Base
Yieldb/%
1
2
3
4
5
6
7
8
9
－
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
K2CO3
KHCO3
65
－
TBAB
－
70
CuI
84
CuI
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
98
CuO
Cu(OAc)2
CuI
71
61
80
CuI
69
CuI
84
a Reaction condition: 4-NI (4 mmol), base (4 mmol), 3b (4 mmol),
It showed that the product of the reaction of 4-NI,
KOH and CuI (Table 4, Entry 2, corresponding to A)
gave equal activity as CuI (Table 1, Entries 3, 7, and 9);
b
Cat. (0.16 mmol), TBAB (0.19 mmol), DMF (10 mL); Isolated
yield.
Table 3 Preparation of some N-aryl-4-nitroimidazoles
Substrate Product
Entry
1
Nitroimidazole
Yield/%
80
O2N
N
Cl
O2N
N
NO2
N
NO2
N
H
NO2
1a
1b
NO2
1c
O2N
O2N
N
N
Cl
O2N
NO2
NO2
2
3
1a
83
NO2
2b
NO2
2c
O2N
O2N
N
N
Cl
O2N
NO2
NH2
NO2
NH2
1a
98
NO2
3b
NO2
3c
Chin. J. Chem. 2013, 31, 243—246
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
245

Hou & Liu
FULL PAPER
Continued
Yield/%
Entry
Nitroimidazole
Substrate
Product
O2N
N
Cl
O2N
NO2
NH2
N
O2N
H2N
NO2
NH2
4
1a
83
75
H2N
NO2
4b
NO2
4c
N
N
Cl
NO2
O2N
N
O2N
H2N
NO2
Cl
N
NO2
5
1a
O2N
NO2
NH2
NO2
5b
5c
Table 4 The results under different conditions to confirm the possible catalytic cyclea
Procedure and result
1
2
3
4
without CuI, yield 70%
Separating the product of the reaction of 4-NI, KOH, CuI and then using it as the catalyst, yield 80%
making ArX and CuI react first, then adding salt of 4-NI, yield 65%
under CuI, yield 98%
a Using 1c as the substrate and TBAB as the additive.
Table 5 Some explosive properties of new compounds
Density/(g/cm3)
Oxygen balance/%
VOD/(km/s)
7.58
Impact sensitivity (H50)/cm
3c
4c
5c
1.73
－
−59
−59
−60
109
167
103
7.72
－
7.62
[4] Jadhav, H. S.; Talawar, M. B.; Sivabalan, R.; Dhavale, D. D.; Ast-
hana, S. N.; Krishnamurthy, V. N. J. Hazard. Mater. 2007, 143, 192.
[5] Duddu, R.; Dave, P. R.; Damavarapu, R.; Surapaneni, R.; Parrish, D.
Synthetic Commun. 2009, 39, 4282.
however, when we changed the order of adding
materials (Table 4, Entry 3, corresponding to B), the
yield decreased to 65%, the same as no catalyst and
additive (Table 1, Entry 1). Thus, we believed that the
possible catalytic cycle was carried out by the way A.
The impact sensitivity of new compounds was cal-
culated according to the reference.[15] VOD was calcu-
lated theoretically with the help of the reference [16].
[6] Duddu, R.; Dave, P. R.; Damavarapu, R.; Gelber, N.; Parrish, D.
Tetrahedron Lett. 2010, 51, 399.
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[9] Searcey, M.; Pye, P. L.; Lee, J. B. Synthetic Commun. 1989, 19,
1309.
Conclusions
In summary, we have investigated and established
that the CuI/TBAB catalytic system is efficient and has
a good yield for preparation of N-aryl-4-nitroimidazole
as potential insensitive energy materials, using chloro-
nitroarene as substrate.
[10] Coburn, M. D.; Neuman, P. N. J. Heterocycl. Chem. 1970, 7, 1391.
[11] Bellina, F.; Rossi, R. Adv. Synth. Catal. 2010, 352, 1223.
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[13] Nair, M. D.; Nagarajan, K. Prod. Drug. Res. 1983, 27, 163.
[14] Complete crystallographic information files for compound 3c has
been deposited with the Cambridge Crystallographic Data Center as
supple-mentary publications CCDC 883593. Copies of this data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ (UK); Tel.: (＋44) 1223-336-408, Fax: (＋44)
1223-336-033, or E-mail: deposit@ccdc. cam. ac. uk.
[15] Lai, W. P.; Lian, P.; Wang, B. Z.; Ge, Z. X. J. Energ. Mater. 2010,
28, 45.
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Chin. J. Chem. 2013, 31, 243—246