Synthesis and anti-tuberculosis activity of N-aryl-C-nitroazoles

Article abstract of DOI:10.1016/j.ejmech.2004.06.014

Twelve N-aryl derivatives of 4-nitroimidazole, 2-methyl-4-nitroimidazole, 4-nitropyrazole or 3-nitro-1,2,4-triazole have been synthesized either by a degenerated ring transformation reaction of 1,4-dinitroimidazoles with 4-substituted anilines or by a condensation of fluoronitrobenzenes with salts prepared from C-nitro-1H-azoles and 1,8-diazabicyclo[5.4.0]-7-undecene. The Tuberculosis Antimicrobial Acquisition and Coordinating Facility has provided anti-mycobacterial data concerning inhibition activity of 12 compounds.

Full text of DOI:10.1016/j.ejmech.2004.06.014

European Journal of Medicinal Chemistry 39 (2004) 849–853
www.elsevier.com/locate/ejmech
Original article
Synthesis and anti-tuberculosis activity of N-aryl-C-nitroazoles
Krzysztof Walczak, Andrzej Gondela, Jerzy Suwin´ski *
Department of Organic Chemistry, Biochemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland
Received 4 November 2003; received in revised form 14 May 2004; accepted 23 June 2004
Available online 11 September 2004
Abstract
Twelve N-aryl derivatives of 4-nitroimidazole, 2-methyl-4-nitroimidazole, 4-nitropyrazole or 3-nitro-1,2,4-triazole have been synthesized
either by a degenerated ring transformation reaction of 1,4-dinitroimidazoles with 4-substituted anilines or by a condensation of fluoronitro-
benzenes with salts prepared from C-nitro-1H-azoles and 1,8-diazabicyclo[5.4.0]-7-undecene. The Tuberculosis Antimicrobial Acquisition
and Coordinating Facility has provided anti-mycobacterial data concerning inhibition activity of 12 compounds.
© 2004 Elsevier SAS. All rights reserved.
Keywords: Arylnitroazoles; Synthesis; Tuberculosis inhibition
1. Introduction
2. Chemistry
For a long time N-aryl derivatives of C-nitro-1H-azoles
have been scarcely known due to serious limitations of
methods potentially useful in the compounds preparation.
The first approach involved nitration of 1-arylazoles. Carbon
atoms of azole rings are less susceptible to electrophiles than
those of benzene. Thus, during nitration of 1-phenylazoles,
nitronium cation is attacking preferably benzene to azole’s
rings [15]. The second approach involved nucleophilic subs-
titution of chlorine or fluorine atom in benzene derivatives by
nitroazoles. Low nucleophilicity of C-nitro-1H-azoles and
poor solubility of their Na or K-salts limited the latter method
to the syntheses of N-(2,4-dinitro- or 4-nitrophenyl)-C-
nitroazoles. Additionally, yields of the obtained products, at
least according to known procedures, are low and purifica-
tion of the derivatives is troublesome [16,17]. We have ela-
borated general methods for the preparation of 1-aryl-4-
nitroimidazoles [18,19] and of 1-aryl-4-nitropyrazoles [20].
Both methods involve degenerated ring transformation (an-
rorc) in reactions of 1,4-dinitroimidazoles or 1,4-
dinitropyrazoles with anilines or phenylhydrazines, respecti-
vely. A detailed anrorc mechanism of the formation of
1-substituted 4-nitroimidazoles has been established
[18,19,21]. The method can be successfully applied to the
synthesis of 1-aryl-4-nitroazoles containing electron-
donating or relatively week electron-withdrawing substitu-
The recent substantial increase in tuberculosis incidence
throughout the world is caused, in many cases, by the drug-
resistant Mycobacterium tuberculosis. The anti-tubercular
strategies based on isoniazid, pyrazin amide, ethambutol,
rifampicin and streptomycin are very often insufficient [1].
This is the major problem in curing tuberculosis in HIV-
infected patients what causes an urgent need for new active
agents. A special interest has been focussed on five membe-
red heterocyclic compounds used very often in the pharma-
cological and medicinal applications. The anti-tuberculosis
activity of pyrrole [2–4], oxadiazole [5], imidazole [6,7],
triazole [8–11] and other heterocyclic systems [12–14] deri-
vatives has been reported. Several of the tested derivatives
have shown promising properties. Nevertheless, none of the
compounds screened as Mycobacterium tuberculosis inhibi-
tors belonged to N-aryl-C-nitroazoles, thus to a group of
compounds synthesized and screened during this work.
* Corresponding author. Tel.: +48-32-2371839; fax: +48-32-2371549.
E-mail address: suwinski@polsl.gliwice.pl (J. Suwin´ski).
0223-5234/$ - see front matter © 2004 Elsevier SAS. All rights reserved.
doi:10.1016/j.ejmech.2004.06.014

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K. Walczak et al. / European Journal of Medicinal Chemistry 39 (2004) 849–853
ents like OH, OR, R, Cl, Br, COOR etc in aryl group [18,20].
The reactions occur under very mild conditions in aqueous
methanol and usually at ambient temperature affording
1-aryl-4-nitroazoles in high yields [18,20]. Very weak nu-
cleophiles (e.g. 2,4-dinitroaniline or 2,4-dinitrophenyl-
hydrazine) do not react with 1,4-dinitroazoles.
In order to introduce 2,4-dinitrophenyl or 4-nitrophenyl
substituent on the pyrrole type nitrogen atom in C-nitro-1H-
azoles we used a reaction of 1-fluoro-2,4-dinitro- or 1-fluoro-
4-nitrobenzene accordingly with nitroazole-1,8-diaza-
bicyclo[5.4.0]-7-undecenium salts [22,23]. This method,
being a modification of a known approach [16], provided the
desired pure derivatives in high yields.
nitroimidazole (3a) and 1-(4-methoxyphenyl)-4-nitro-
imidazole (3b), respectively. A similar treatment of
2-methyl-1,4-dinitroimidazole (1b) with 2a,b or
4-chloroaniline (2c) gave appropriate 1-(4-substituted)-2-
methyl-4-nitroimidazoles (Scheme 1). After a single crystal-
lization analytically pure products were obtained in yields
exceeding 75%.
Eight 2,4-dinitrophenyl- or 4-nitrophenyl derivatives of
4-nitroimidazole (4a–b), 4-nitropyrazole (4c) and of 3-nitro-
1,2,4-triazole (4d) were obtained by a two-step synthesis. At
first suspensions of 4a–d in tetrahydrofuran were treated
with equimolar amounts of 1,8-diazabicyclo[5.4.0]-7-
undecene (5) at about 25 °C for 2 h. On cooling the reaction
mixtures deposited solids of the forming salts 6. The salts
were collected, rinsed with n-pentane and dried to give 6a–d,
ready for the use in a next step.
3. Biological tests
Dry salts 6a–d were dissolved in dimethylformamide and
treated with fluoronitrobenzenes 7a–b at 25 °C for 24 h. The
reaction mixtures on dilution with icy water deposited
gummy solids, which were crystallized to afford pure prod-
ucts 8a–h (Scheme 2). All the obtained compounds were
characterized by sharp melting points, correct elemental
analyses, 1H NMR and 13C NMR spectra.
Anti-mycobacterial data concerning 12 N-aryl-C-
nitroazoles tested as inhibitors against Mycobacterium tu-
berculosis are collected in Table 1. In the primary assay four
compounds shown distinctive activity. Among 1-aryl-4-
nitroimidazoles without nitro groups at 1-aryl substituent
only 1-(4-chlorophenyl-2-methyl-4-nitroimidazole (3c)
Biological primary in vitro tests against Mycobacterium
tuberculosis H37Rv (ATCC 27294) for 12 N-aryl-C-
nitroazoles at concentrations of 6.25 µg/ml were carried out
in Southern Research Institute in BACTEC 12 B medium,
using a broth micro dilution assay, the Micro plate Alamar
Blue Assay (MABA). Data from the primary assay (level 1)
revealed four active compounds (effecting >90% inhibition).
Afterwards they have been tested in minimum inhibitory
concentration (MIC) assay (level 2). Three of them, namely
3c, 8e and g were also tested at level 2 in cytotoxicity (IC50)
assays. MIC and IC50 values for those three 1-aryl-
nitroazoles to VERO cell line in culture media were deter-
mined and selectivity indexes (SI = MIC/IC50) were calcu-
lated. The Tuberculosis Antimicrobial Acquisition and
Coordinating Facility (TAACF) provided all biological data
through a research and development contract with the US
National Institute of Allergy and Infectious Diseases.
4. Results and discussion
Five 1-aryl-4-nitroimidazoles were obtained by the anrorc
reaction. Treatment of 1,4-dinitroimidazole (1a) with
4-bromoaniline (2a) or 4-methoxyaniline (2b) in aqueous
methanol at 25 °C for 24 h afforded 1-(4-bromophenyl)-4-
Scheme 1
.
Scheme 2
.

K. Walczak et al. / European Journal of Medicinal Chemistry 39 (2004) 849–853
851
Table 1
Tuberculosis inhibition test (Alamar) preliminary results
Compound
Azole
Azole ring
substituents
4-NO2
4-NO2
4-NO2
2-CH3
Benzene
substituents
4-Br
ring MIC a
(µg/ml)
>6.25
Inhibition (%)
and activity
No.
3a
3b
8c
Imidazole
Imidazole
Imidazole
Imidazole
76
0
4-CH3O
4-NO2
>6.25
>6.25
0
3c
4-Cl
<6.25
99
+
4-NO2
2-CH3
3d
3e
8b
8d
8e
8f
Imidazole
Imidazole
Imidazole
Imidazole
Pyrazole
4-CH3O
4-Br
>6.25
>6.25
<6.25
>6.25
<6.25
>6.25
<6.25
>6.25
0
4-NO2
2-CH3
–
85
4–NO2
2-CH3
2,4-diNO2
4-NO2
91
+
4-NO2
2-CH3
83
–
4-NO2
4-NO2
2,4-diNO2
4-NO2
96
+
Pyrazole
4-NO2
3-NO2
3-NO2
11
–
8g
8h
1,2,4-Triazole
1,2,4-Triazole
2,4-diNO2
4-NO2
99
+
7
–
a MIC at a single concentration 6.25 µg/ml (by MABA in BACTEC 12B medium against Mycobacterium tuberculosis H37Rv); inhibition over 90% indicates
activity designated by +.
Table 2
demonstrated sufficient activity (99% of inhibition at
Tuberculosis inhibition activity and cytotoxicity assays summary a concer-
ning compounds 3c, 8e and g
6.25 µg/ml), others derivatives were considered as inactive
though bromo derivatives 3a and 3e were characterized by
76% and 85% inhibition, respectively.
Compound
MIC assay (level 2) and cytotoxicity assay
Inhib. (%) MIC (µg/ml) IC50 (µg/ml) SI
Three N-(2,4-dinitrophenyl)-C-nitroazole derivatives
(8b,e and g) proved to be active in the primary screen with
inhibition over 90%. In contrast to that four tested N-(4-
nitrophenyl)-C-nitroazoles (8c,d,f and h) shown inhibition
ranging only from 83% for 8d (2-methyl-4-nitroimidazole
derivative) to 0% for a similar compound 8c lacking
2-methyl group at imidazole ring. Thus, inhibition activity of
8b,e and g can rather be attributed to the 2,4-dinitrophenyl
fragment than to C-nitroazolyl ones, (Table 1) [11].
3c
8e
8g
INH
99
0.39
>62.5
0.40
>160
0.06
96
6.25
99
6.25
0.39
0.06
>99
<0.05
<0.125
>1 000
>100
>40 000
>800
RMP
>99
a Inhib.—inhibition; MIC—minimum inhibitory concentration (generally
MIC <1 µg/ml is an excellent lead); IC50—toxicity to a VERO cell line;
SI—selectivity index defined as the ratio of IC50 to MIC (it should be >10
for further testing).
It is not easy to draw further conclusions concerning
structure–inhibition activity relationship basing on the ob-
tained results. Nevertheless, it seems clear that electron-
donating substituent on 1-nitrogen atom in C-nitro-
imidazoles diminishes inhibition activity of the compounds.
Surprisingly, it also appears that 2-methyl-4-nitroimidazoles
are more active than 4-nitroimidazoles. These assumptions
can be supported by results of the similar tests on a series of
N-alkyl-C-nitroimidazoles (containing additional substitu-
ents in the N-alkyl chain) among which unfortunately none
demonstrated inhibition activity over 20%.1
the data for control drugs INH and RMP. Discouraging low
solubility of N-(2,4-dinitrophenyl)-C-nitroazoles 8e and g
restrained their further screening.
5. Conclusions
None of the tested compounds demonstrated tuberculosis
inhibition activity and cytotoxicity results better or at least
similar to the control drugs isoniazid (INH) and rifampicin
(RMP). Microphage assay (level 3) probably will not be
carried out even with 1-(4-chlorophenyl)-2-metyhyl-4-
nitroimidazole (3c). Nevertheless, the results obtained with
the latter compound has encouraged us to the preparation of
other N-aryl-C-nitroazoles particularly containing N-(halo-
phenyl)- and N-(dihalophenyl) substituents, which can bring
more promising results. Syntheses and tuberculosis inhibi-
tion activity of these new compounds will be published in
due time.
More promising tuberculosis inhibitors 3c, 8e and g were
tested at level 2 in MIC and cytotoxicity assays. Important
results of those assays are disclosed in Table 2 together with
1 Examples: 1-(2-Hydroxy-3-methoxypropyl)-2-methyl-4-nitro-1H-imi-
dazole and (R)-(+)-1-(2,3-dihydroxypropyl)-2-methyl-4-nitro-1H-imi-
dazole exhibit inhibition of 2% and 16%, respectively.

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K. Walczak et al. / European Journal of Medicinal Chemistry 39 (2004) 849–853
6. Experimental
J = 8.7 Hz, H-2, H-6), 2.33 (s, 3H, CH3); 13C NMR: d (ppm):
146.17, 144.74, 134.98, 132.60 (2C), 127.98 (2C), 122.62,
122.56, 13.41 (CH3). Anal.: C10H8BrN3O2.
Melting points are uncorrected. Elemental analyses were
performed on Perkin-Elmer 240C apparatus and were correct
1
within acceptable errors. H and 13C spectra were recorded
6.2. A general procedure for preparation
of C-nitroazole-DBU salts 6a–d
on a Varian (300 and 75.5 MHz) spectrometer in DMSO-d6
solutions with TMS as an internal standard.
Dinitroimidazoles 1a–b were prepared as described by us
elsewhere [24]. 4-Nitropyrazole was prepared according to
the reported procedure [25]. 3-Nitro-1,2,4-triazole and other
starting reagents and solvents were purchased form Aldrich.
1,8-Diazabicyclo[5.4.0]-7-undecene (5, 10 mmol) was
added dropwise into a stirred solution of C-nitroazole (4a–d,
10 mmol) in tetrahydrofuran (5 ml) at 25 °C. Ten minutes
later the resulting mixture (containing already some precipi-
tations) was cooled down to circa –10 °C and left at this
temperature for 1 h. The precipitations were collected,
washed with cold n-pentane (10 ml) and dried in vacuum
desiccator over solid sodium hydroxide.
6.1. A general procedure for the synthesis
of arylimidazoles (3a–e)
A solution of dinitroimidazole (1a or 1b, 5 mmol) and
amine (2a–c, 5 mmol) in aqueous methanol (10 ml, 1:9) was
stirred in a closed vessel at 25 °C for 24 h and then poured
into cold water. The precipitated solids were separated and
crystallized from methanol or acetone to yield pure products
3a–e.
6.2.1. (4-Nitropyrazole)-DBU salt (6c)
Yield 94%, m.p. 114–115 °C. It was analysed and used
without further purification. Anal.: C12H19N5O2.
6.1.1. 1-(4-Bromophenyl)-4-nitro-1H-imidazole (3a)
Yield 92%, m.p. 213–214 °C. 1H NMR: d (ppm): 8.99 (d,
1H, J = 1.5 Hz, H-5imid), 8.47 (d, 1H, J = 1.5 Hz, H-2imid),
7.76 (m, 4H, C6H4); 13C NMR: d (ppm): 148.12, 135.42,
134.69, 132.65, 123.20, 122.94, 121.26, 119.43. Anal.:
C9H6BrN3O2.
6.2.2. (3-Nitro-1,2,4-triazole)-DBU salt (6d)
Yield 77%, m.p. 143–144 °C. Anal.: C11H18N6O2.
6.2.3. (C-Nitro-NH-azoles)-DBU salts 6a–b
They had properties as described by us earlier (6a: m.p.
75–76 °C, lit. [23] 74–75 °C; 6b: m.p. 102–103 °C, lit. [22]
103–104 °C).
6.1.2. 1-(4-Methoxyphenyl)-4-nitro-1H-imidazole (3b)
Yield 90%, m.p. 189–190 °C. 1H NMR: d (ppm): 8.91 (d,
1H, J = 1.5 Hz, H-5imid), 8.37 (d, 1H, J = 1.5 Hz, H-2imid),
7.72 (dd, 2H, J = 2.1 Hz, 6.8 Hz, H-3, H-5), 7.12 (2H,
J = 2.1 Hz, 6.8 Hz, H-2, H-6), 3.83 (s, 3H, OCH3); 13C NMR:
d (ppm): 159.25, 147.87, 135.65, 128.69, 122.96 (2C),
119.90, 114.93 (2C), 55.60 (OCH3). Anal.: C10H9N3O3.
6.3. A general procedure for the preparation
of N-aryl-C-nitroazoles 8a–g
To nitroazole-DBU salt (6a–d, 10 mmol), dissolved in
dimethylformamide (7 ml), fluoronitroarene (7a–b,
10 mmol) in dimethylformamide (3 ml) was added. Samples
of the resulting solution, stirred at ambient temperature, were
analysed from time to time by TLC. When a reaction was
completed (30 min to 24 h—the times of a decay of the
starting material spots on TLC plate), the reaction mixture
was poured onto ice–water mixture (50 g: 50 ml). The pre-
cipitations were collected, crystallized from ethyl acetate–
methanol (1:3) mixture and dried on air. Crude gummy
1-(2,4-dinitrophenyl)-4-nitropyrazole (8e) before crystalli-
zation was dissolved in ethyl acetate. The latter solution was
dried over magnesium sulphate; then the solvent was re-
moved and the residue crystallized as usual.Yields and prop-
erties of crystallized products 8a–g are given below.
6.1.3. 1-(4-Chlorophenyl)-2-methyl-4-nitro-1H-imidazole
(3c)
Yield 84%, m.p. 107–108 °C. 1H NMR: d (ppm): 8.59 (s,
1H, H-5imid), 7.72–7.66 (m, 4H, Ar), 2.32(s, 3H, CH3); 13
C
NMR: d (ppm): 146.17, 144.80, 134.57, 134.12, 129.66 (2C),
127.75 (2C), 122.64, 119.02, 13.41 (CH3). Anal.:
C10H8ClN3O2.
6.1.4. 1-(4-Methoxyphenyl)-2-methyl-4-nitro-1H-imidazole
(3d)
Yield 92%, m.p. 124–125 °C. 1H NMR: d (ppm): 8.50 (s,
1H, H-5imid), 7.54 (d, 2H, J = 9.0 Hz, H-3, H-5), 7.11 (d, 2H,
J = 9.0 Hz, H-2, H-6), 3.84 (s, 3H, OCH3), 2.28 (s, 3H, CH3);
13C NMR: d (ppm): 159.73, 145.95, 144.98, 128.52, 127.16
(2C), 122.79, 114.70 (2C), 55.56 (OCH3), 13.30 (CH3).
Anal.: C11H11N3O3.
6.3.1. 1-(2,4-Dinitrophenyl)-4-nitro-1H-imidazole (8a)
Yield 80%; m.p. 153–154 °C, (154–156 °C dec. [17]) 1H
NMR: d (ppm): 9.09 (d, 1H, J = 2.7 Hz, H-3), 8.88 (d, 1H,
J = 1.5 Hz, H-5imid), 8.79 (dd, 1H, J = 2.7 Hz, 8.7 Hz, H-5),
8.28 (d, 1H, J = 1.5 Hz, H-2 imid), 8.19 (d, 1H, J = 8.7 Hz,
H-6). 13C NMR: d (ppm): 147.95, 147.81, 137.78, 133.52,
131.60. 129.26, 122.61, 121.44. Anal.: C9H5N5O6.
6.1.5. 1-(4-Bromophenyl)-2-methyl-4-nitro-1H-imidazole
(3e)
Yield 89%, m.p. 124–125 °C. 1H NMR: d (ppm): 8.59 (s,
1H, H-5imid), 7.80 (d, 2H, J = 8.7 Hz, H-3, H-5), 7.60 (d, 2H,

K. Walczak et al. / European Journal of Medicinal Chemistry 39 (2004) 849–853
853
6.3.2. 1-(2,4-Dinitrophenyl)-2-methyl-4-nitro-1H-imidazole
(8b)
J = 9.0 Hz, H-3, H-5). 13C NMR: d (ppm): 147.21, 145.95,
140.11, 125.58, 121.02, tiazole C-3 not observed.
Yield 83%, m.p. 191–192 °C (194–196 °C [17]); 1H
NMR: d (ppm): 9.03 (d, 1H, J = 2.4 Hz, H-6), 8.80 (dd, 1H,
J = 2.4 Hz, 8.7 Hz, H-5), 8.66 (s, 1H, H-5imid), 8.23 (d, 1H,
J = 8.7 Hz, H-3), 2.41(s, 3H, Me). 13C NMR: d (ppm):
148.33, 146.71, 145.70, 144.99, 133.30, 132.72, 129.49,
122.98, 121.52. Anal.: C10H7N5O6 (C, H, N,O).
Acknowledgements
Anti-mycobacterial data were provided by the Tuberculo-
sis Antimicrobial Acquisition and Coordinating Facility
(TAACF) at Southern Research Institute in Alabama through
a research and development contract with the US National
Institute of Allergy and Infectious Diseases.
6.3.3. 1-(4-Nitrophenyl)-4-nitro-1H-imidazole (8c)
Yield 77%; m.p. 190–191 °C (188–190 °C dec. [17]). 1H
NMR: d (ppm): 9.18 (d, 1H, J = 1.5 Hz, H-5imid), 8.66 (d,
1H, J = 1.5 Hz, H-2), 8.43 (dd, 2H, J = 2.1 Hz, 9.0 Hz, H-3,
H-5), 8.14 (dd, 2H, J = 2.1 Hz, 9.0 Hz, H-2, H-6). 13C NMR:
d (ppm): 148.43, 146.58, 140.14, 135.84, 125.29, 121.90,
119.56. Anal.: C9H6N4O4 (C, H, N, O).
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d (ppm): 9.74 (s, 1H, H-5pyr), 8.94 (d, 1H, J = 2.4 Hz, H-3),
8.74 (dd, 1H, J = 2.4 Hz, 8.7 Hz, H-5), 8.66 (s, 1H, H-3pyr),
8.28 (d, 1H, J = 8.7 Hz, H-6). 13C NMR: d (ppm): 147.09,
143.37, 138.38, 137.41, 134.91, 132.10, 128.41, 127.84,
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(1994) 1141.
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[17] R. Kilnk, L. Hepding, Brit. Pat. 1 (133) (1969) 408 ((13 Nov 1968);
CA: 70:47456p).
6.3.6. 4-Nitro-1-(4-nitrophenyl)-1H-pyrazole (8f)
Yield 90%, m.p. 162–163 °C. 1H NMR: d (ppm): 9.86 (s,
1H, H-5pyr), 8.64 (s, 1H, H-3pyr), 8,41 (d, 2H, J = 8,4 Hz,
H-2, H-6), 8.24 (d, 2H, J = 8.4 Hz, H-3, H-5). 13C NMR: d
(ppm): 146.29, 142.62, 137.89, 137.54, 129.26, 125.31.
119.97. Anal.: C9H6N4O4.
[18] (a) E. Salwin´ska, J. Suwin´ski, Polish J. Chem. 64 (1990) 813;
´
(b) J. Suwin´ski, W. Pawlus, E. Salwin´ska, K. Swierczek, Heterocycles
6.3.7. 1-(2,4-Dinitrophenyl)-3-nitro-1H-[1,2,4]-triazole
(8g)
37 (1994) 1511; (c) J. Suwin´ski, W. Szczepankiewicz, M. Wideł,
Archiv. Pharm. 325 (1992) 317 (Weinheim, Ger.).
[19] J. Suwin´ski, W. Szczepankiewicz, J. Labelled Comp. Radiopharm. 38
(1996) 395.
[20] J. Suwin´ski, M. Sawicki, P. Wagner, Communicate on 10th Blue
Danube Symposium on Heterocyclic Chemistry (PO-181), September
2003, Vienna/Austria.
[21] H. Llempen, E. Salwin´ska, J. Suwin´ski, W. Szczepankiewicz, Polish J.
Chem. 66 (1992) 943.
Yield 75%, m.p. 103–104 °C (98–100 °C [16]). 1H NMR:
d (ppm): 9.55 (s, 1H, H-5triazole), 9.02(d, 1H, J = 2.4 Hz,
H-3), 8.33(dd, 1H, J = 2.4 Hz, 8.7 Hz, H-5), 8.34(d, 1H,
J = 8.7 Hz, H-6). 13C NMR: d (ppm): 162.97, 148.52, 148.12,
143.17, 132.32, 129.78, 129.08, 121.53. Anal.: C8H4N6O6.
[22] K. Walczak, J. Suwin´ski, Polish J. Chem. 70 (1996) 861.
[23] K. Walczak, J. Suwin´ski, Polish J. Chem. 72 (1998) 1028.
[24] J. Suwin´ski, E. Salwin´ska, Polish J. Chem. 61 (1987) 913.
[25] R. Huttle, F. Buchele, Chem. Ber. 88 (1955) 1586.
6.3.8. 3-Nitro-1-(4-nitrophenyl)-1H-[1,2,4]-triazole (8h)
Yield 34%, m.p. 200–201 °C dec. 1H NMR: d (ppm): 9.78
(s, 1H, H-5), 8.51(d, 2H, J = 9.0 Hz, H-2, H-6), 8.25 (d, 2H,