Synthesis of 2-R-4,6-dinitro-2h-indazoles from 2,4,6-trinitrotoluene

Article abstract of DOI:10.1055/s-2000-7120

An efficient synthesis of 2-R-4,6-dinitro-2H-indazoles (R = aryl or substituted amine) from 2,4,6-trinitrotoluene was elaborated. The proposed method includes formation of C-(2,4,6-trinitrophenyl)-N-R-azomethines 1 (a-g) from TNT or the product of its transformation 2,4,6-trinitrobenzaldehyde (TNBA) with the further regiospecific substitution of the ortho-nitro group in 1 (a-g) by the azido group under the action of NAN₃. Thermolysis of the azides 2 (a-g) gives previously unknown 2-R-4,6-dinitro-2H-indazoles 3 (a-g) in high yields.

Full text of DOI:10.1055/s-2000-7120

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PAPER
Synthesis of 2-R-4,6-Dinitro-2H-indazoles from 2,4,6-Trinitrotoluene
Alexander M. Kuvshinov, Valentina I. Gulevskaya, Vladimir V. Rozhkov, Svyatoslav A. Shevelev*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp., 47, 117913, Moscow, Russia
Fax +7(095)1355328; E-mail: shevelev@cacr.ioc.ac.ru
Received 26 April 2000
2). This method turned out to be more efficient than the al-
ready described condensation of TNBA with anilines in
acetic acid.7 Hydrazones of TNBA 1(e, g) were synthe-
sised by condensation of TNBA with corresponding hy-
Abstract: An efficient synthesis of 2-R-4,6-dinitro-2H-indazoles
(R = aryl or substituted amine) from 2,4,6-trinitrotoluene was elab-
orated. The proposed method includes formation of C-(2,4,6-trini-
trophenyl)-N-R-azomethines 1 (a-g) from TNT or the product of its
transformation 2,4,6-trinitrobenzaldehyde (TNBA) with the further drazines (Scheme 2, Tables 1 and 2).
regiospecific substitution of the ortho-nitro group in 1 (a-g) by the
The interaction of NaN3 with azomethines 1 in DMF at
azido group under the action of NaN3. Thermolysis of the azides 2
(a-g) gives previously unknown 2-R-4,6-dinitro-2H-indazoles 3
(a-g) in high yields.
20 ∞C leads to regiospecific substitution of the ortho-nitro
group with the formation of corresponding azides 2. In the
case of 2(a, f), the azides were isolated and identified
(Schemes 1, 2; Tables 1, 2) while azides 2(e, g) were used
without purification.
Key words: 2,4,6-trinitrotoluene, 2,4,6-trinitrobenzaldehyde,
azomethines, aromatic nucleophilic substitution, aromatic azides,
2-R-4,6-dinitro-2H-indazoles
Thermolysis of azides 2(a, e-g) in ethylene glycol at
150-180 ∞C gives the corresponding 2-R-4,6-dinitro-2H-
Previously, within the framework of the project directed indazoles 3 (a, e-g) (Schemes 1, 2; Tables 1, 2). Ben-
towards the chemical utilisation of the explosive 2,4,6- zylideneanilines 1b-d convert into indazoles even in the
trinitrotoluene (TNT),1 we described a general method for process of the azide formation, which was proven by 1H
the synthesis of 2-aryl-4,6-dinitroindoles. The crucial NMR analysis of the reaction mixture. Thus, the conver-
point in the suggested method was regiospecific substitu- sion of azides 2b-d takes place in DMF at room temper-
tion of the ortho-nitro group in 1-(2,4,6-trinitrophenyl)-2- ature and according to the data obtained, the rate of the
arylethenes (products of condensation of TNT with aro- conversion of the azides is close to that of their formation.
matic aldehydes) by the azido group, under the action of Actually, notwithstanding the fact that the formation of
NaN3.2
azides 2b-d was spectroscopically detected, in all in-
stances the presence of indazoles 3b-d was also observed
before the complete conversion of azomethines 1b-d. To
our knowledge, thermolysis of azides under such mild
conditions with the formation of 2H-indazoles was ob-
served for the first time.
We presumed, that the selectivity of the substitution was
governed by the steric effect of the b-arylvinylic fragment
under the influence of which the ortho-nitro group was
turned through a considerable angle. This phenomenon fa-
cilitates the nucleophilic substitution of the nitro group.2
As a result of our investigation, an efficient synthesis of
previously unknown 2-R-amino-4,6-dinitro-2H-indazoles
(R = aryl or substituted amine) from the readily available
2,4,6-trinitrotoluene has been elaborated.
In accordance with the obtained results, we examined sub-
stitution of the nitro group by N3 in C-(2,4,6-trinitrophe-
nyl)azomethines. In this case, if the selectivity of the
ortho-nitro group substitution was maintained, we could
–
expect that the resulting compounds containing the azido As stated above, such a selective substitution of the ortho-
group ortho to C=N bond, when thermolised, would give nitro group in azomethines 1 can be connected, like in the
corresponding 2-R-2H-indazoles.3,4
case of 1-(2,4,6-trinitrophenyl)-2-arylethenes, with the
considerable turn of this nitro group relative to the aro-
matic ring. Quantum-chemical calculations (AM1,
Chem3D Pro 5.0) show that for 1a and 1e the 2-NO2
group is turned through 35 and 40 degrees, respectively,
the 6-NO2 group is turned by 9 and 20 degrees, and the
4-NO2 group lies in the plane of the aromatic ring. For
2,4,6-(NO2)3C6H2CH=CHC6H5, the same method gives
the following angles: 2-NO2: 63∞, 6-NO2: 29∞ and 4-NO2:
0∞. The method specified, adequately reflects the experi-
mental conformational data for 1-X-2,4,6-trinitroben-
zenes (X = Me8,9 and Cl9,10).
We examined two types of C-(2,4,6-trinitrophe-
nyl)azomethines: N-(2,4,6-trinitrobenzylidene)anilines
1(a-d), their pyrazolic analogue 1e and hydrazones of
2,4,6-trinitrobenzaldehyde6 1(f, g).
Azomethine 1a was synthesised by the condensation of
TNT with para-nitroso-N,N-dimethylaniline in pyridine
in the presence of a catalytic amount of iodine.5,6 Acid hy-
drolysis of 1a leads to 2,4,6-trinitrobenzaldehyde6 (TN-
BA), Scheme 1.
Other N-(2,4,6-trinitrobenzylidene)anilines 1(b-d) and
their heterocyclic analogue 1e were obtained in high
yields by condensation of TNBA with aromatic amines in
benzene in the presence of TsOH (Scheme 2, Tables 1 and
Mps were determined using a Boetius apparatus and are uncorrect-
ed. Mass spectra (EI) were recorded on MS-30 (Kratos) spectrome-
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Synthesis of 2-R-4,6-Dinitro-2H-indazoles from 2,4,6-Trinitrotoluene
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Scheme 1
ter. All reactions were monitored by TLC using Silufol precoated
aluminiun plates, which were visualized with UV light. H NMR
spectra were measured on a Bruker AC 200 spectrometer. Chemical
shifts (d) are reported in ppm downfield from TMS. Organic sol-
vents and reagents were purified by the accepted literature proce-
dures. For all new compounds, satisfactory microanalyses were
1
obtained. 1H NMR and mass parameters along with the yields and
mps are given in Tables 1 and 2. 13C NMR spectra were not mea-
sured due to the poor solubility of the obtained compounds.
Scheme 2
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A. M. Kuvshinov et al.
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Table 1 Yields, Mps and MS Parameters of Azomethines 1, Azides 2 and Indazoles 3
Compounda
Yieldsb (%)
70
Mp (∞C) (Solvent)
MS (EI) m/z (%)
1a
>250 (EtOH)
[M+,359(0)], 330 (84), 313 (9), 299 (11), 147 (22), 135 (100), 121 (64), 77
(69), 63 (66), 76 (46)
1b
1c
1d
1e
1f
63
67
71
75
93
60
70
90
87
68
65
170-171c (EtOH)
190-191 (MeCN)
171-172 EtOH)
189-190 (EtOH)
252-254d (MeCN)
182-183 (iPrOH)
175 (dec) (MeCN)
203 (dec) (MeCN)
196-198 (MeCN)
208 (dec) (EtOH)
243 (dec) (MeCN)
316 (57), 299 (87), 284 (41), 269 (23), 165 (48), 151 (83), 105 (41), 93 (59),
77 (100)
346 (84), 314 (9), 299 (11), 147 (22), 135 (100), 121 (64), 77 (69), 63 (66),
76 (46)
334 (20), 302 (21), 227 (10), 196 (23), 169 (57), 123 (31), 110 (47), 95 (85),
58 (66)
348 (65), 316 (10), 210 (13), 195 (11), 137 (19), 124 (81), 82 (77), 67 (70),
56 (100)
[M+, 376(0)], 329 (100), 299 (11), 237 (18), 207 (11), 191 (21), 164 (20), 88
(15), 76 (16), 63 (15)
1g
2a
2f
[M+, 283(0)], 309 (14), 222 (3), 145 (8), 130 (29), 118 (7), 103 (13), 75 (17),
58 (95), 43 (100)
[M+, 355(0)], 327 (100), 298 (73), 252 (43), 235 (45), 208 (24), 150 (26),
135 (51), 120 (37), 77 (22)
[M+, 372(0)], 329 (100), 299 (29), 253 (9), 236 (12), 207 (11), 191 (18), 164
(16), 88 (13), 76 (17)
3a
3b
3c
[M+, 327(0)], 306 (7), 104 (25), 119 (89), 91 (73), 76 (24), 65 (28), 50 (19),
44 (100)
284 (100), 252 (8), 238 (13), 206 (14), 192 (34), 164 (39), 116 (17), 77 (80),
50 (40)
314 (100), 299 (15), 257 (28), 239 (30), 222 (24), 195 (21), 146 (28), 92
(47), 77 (69)
3d
3e
67
80
222 (dec) (EtOH)
>250 (MeCN)
302 (78), 272 (13), 226 (26), 210 (41), 182 (48), 162 (55), 95 (10), 43 (100)
316 (95), 300 (6), 274 (6), 246 (6), 224 (8), 183 (12), 155 (7), 109 (5), 56
(100)
3f
85
205-206 (MeCN)
[M+, 344(0)], 329 (100), 299 (25), 237 (16), 207 (15), 191 (15), 180 (3), 164
(13), 76 (14), 50 (11)
3g
70
200 (dec) (EtOH)
Non volatile
a Satisfactory microanalyses obtained: C 0.25, H 0.28, N 0.33.
b The yields refer to isolated products without further optimization.
c Lit.,7 mp: 170-171∞C.
d Lit.,11 mp: 247∞C.
2,4,6-Trinitrobenzaldehyde6
p-Nitrophenylhydrazone of 2,4,6-Trinitrobezaldehyde (1f)
p-Nitrophenylhydrazine (2.3 g, 15 mmol) was dissolved in concd
H2SO4 (14 mL) and to this solution H2O (21 mL) was carefully add-
ed, followed by EtOH (100 mL). Then, the solution of 2,4,6-trini-
trobenzaldehyde (3 g, 12 mmol) in hot EtOH (10 mL) was added.
The mixture was stirred for 10 min and the precipitated hydrazone
1f was collected by filtration, washed with H2O, and recrystallised.
1H NMR (DMSO-d6): d = 9.12 (s, 2H, Harom), 10.51 (s, 1H, CHO).
EIMS: m/z = 240 [M+] (2), 213 (15), 209 (28), 148 (14), 135 (14),
120 (50), 107 (16), 91 (52), 74 (100).
Azomethines 1 (b-e); General Procedure
A mixture of 2,4,6-trinitrobenzaldehyde (3 mmol) and aromatic
amine (3.1 mmol) in benzene (50 mL) was refluxed in the presence
of TsOH until the complete conversion of the starting material
(1-2 h, TLC). The solvent was evaporated in vacuo, and the residue
recrystallised from an appropriate solvent. Azomethine 1a was ob-
tained according to the previously described procedure.5,6
N,N-Dimethylhydrazone of 2,4,6-Trinitrobenzaldehyde (1g)
Me2NNH2 (0.8 g, 13 mmol) in EtOH (10 mL) was added to a stirring
warm solution of 2,4,6-trinitrobenzaldehyde (2 g, 8.3 mmol) in
EtOH (10 mL). The reaction mixture was stirred at r.t. for 3 d, then
poured into H2O. The precipitated solid was filtered off and recrys-
tallised.
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Synthesis of 2-R-4,6-Dinitro-2H-indazoles from 2,4,6-Trinitrotoluene
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Table 2 1H NMR Parameters of Azomethines 1, Azides 2 and Indazoles 3
Compound
1H NMR (DMSO-d6, TMS), d (ppm), J (Hz)
3.03 (s, 6H, Me2N), 6.81 (m, 2H, AA¢BB¢, p-Me2NPh), 7.71 (m, 2H, AA¢BB¢, p-Me2NPh), 8.88 (s, 1H, CH=N),
1a
9.04 (s, 2H, Harom
)
1b
1c
7.16 (m, 2H, ABB¢CC¢, Ph), 7.31 (m, 1H, ABB¢CC¢, Ph), 7.42 (m, 2H, ABB¢CC¢, Ph), 8.97 (s, 1H, CH=N), 9.14
(s, 2H, Harom
)
3.80 (s, 3H, MeO), 7.05 (m, 2H, AA¢BB¢, p-MeOPh), 7.26 (m, 2H, AA¢BB¢, p-MeOPh), 8.95 (s, 1H, CH=N),
9.12 (s, 2H, Harom
7.30 (m, 4H, AA¢BB¢X, p-FPh), 8.99 (s, 1H, CH=N), 9.15 (s, 2H, Harom
2.20 (s, 3H, Me-Pyrrazole), 2.22 (s, 3H, Me-Pyrrazole), 3.66 (s, 3H, NMe-Pyrrazole), 8.76 (s, 1H, CH=N), 9.04
)
1d
1e
)
(s, 2H, Harom
7.03 (m, 2H, AA¢BB¢, p-NO2Ph), 8.18 (m, 2H, AA¢BB¢, p-NO2Ph), 8.26 (s, 1H, CH=N), 9.01 (s, 2H, Harom
3.28 (s, 3H, NMe), 3.65 (s, 3H, NMe), 7.52 (s, 1H, CH=N), 8.20 (s, 2H, Harom
)
1f
)
1g
2a
)
3.01 (s, 6H, Me2N), 6.77 (m, 2H, AA¢BB¢, p-Me2NPh), 7.75 (m, 2H, AA¢BB¢, p-Me2NPh), 8.45 (s, 1H, CH=N),
8.45 (d, 1H, Harom, 4J = 2.2), 8.53 (d, 1H, Harom, 4J = 2.2)
2f
8.19 (m, 2H, AA¢BB¢, p-NO2Ph), 8.52 (m, 2H, AA¢BB¢, p-NO2Ph), 8.86 (d, 1H, Harom, 4Jab = 2.2), 9.12 (d, 1H,
Harom, 4Jab = 2.2), 9.12 (s, 1H, CH=N)
3a
3b
3c
3d
3e
3f
3.31 (s, 6H, Me2N), 6.88 (m, 2H, AA¢BB¢, p-Me2NPh), 8.06 (m, 2H, AA¢BB¢, p-Me2NPh), 8.72 (d, 1H, Harom
5J = 0.9), 9.17 (dd, 1H, Harom, 4J = 2.1, 5J = 0.9), 9.49 (d, 1H, Harom, 4J = 2.1)
,
7.64 (m, 2H, ABB¢CC¢, Ph), 8.25 (m, 2H, ABB¢CC¢, Ph), 8.73 (d, 1H, Harom, 5J = 0.8 ), 9.28 (d, 1H, Harom
4J = 2.2 ), 9.72 (dd, 1H, Harom, 4J = 2.2, 5J = 0.8)
,
3.87 (s, 3H, MeO), 7.15 (m, 2H, AA¢BB¢, p-MeOPh), 8.14 (m, 2H, AA¢BB¢, p-MeOPh), 8.69 (d, 1H, Harom
,
5J = 1.0), 9.16 (d, 1H, Harom, 4J = 2.1 ), 9.53 (dd, 1H, Harom, 4J = 2.1, 5J = 1.0)
7.47 (m, 2H, AA¢BB¢X, p-FPh), 8.25 (m, 2H, AA¢BB¢X, p-FPh), 8.67 (d, 1H, Harom, 5J = 0.7), 9.16 (d, 1H, Harom
4J = 2.4), 9.61 (dd, 1H, Harom, 4J = 2.4, 5J = 0.7)
,
2.18 (s, 3H, Me-Pyrrazole), 2.30 (s, 3H, Me-Pyrrazole), 3.74 (s, 3H, NMe-Pyrrazole), 8.72(d, 1H, Harom
,
5J = 0.9), 9.16 (d, 1H, Harom, 4J = 2.1), 9.22 (d, 1H, Harom, 4J = 2.1)
8.18 (m, 2H, AA¢BB¢, p-NO2Ph), 8.50 (m, 2H, AA¢BB¢, p-NO2Ph), 8.86 (d, 1H, Harom, 4J = 1.6), 9.05 (d, 1H,
Harom, 5J = 0.7), 9.08 (dd, 1H, Harom, 4J = 1.6, 5J = 0.7)
3g
3.06 (s, 3H, NMe), 3.23 (s, 3H, NMe), 7.57 (s, 1H, Harom), 8.46 (d, 1H, Harom, 4J = 2.0), 8.84 (d, 1H, Harom
4J = 2.0)
,
Azides 2a, 2 e-g and Indazoles 3b-d
Isolation of indazole 3a: the reaction mixture was poured into H2O
(75 mL), the product filtered off and purified by column chromatog-
raphy (silica gel 35-63, benzene).
NaN3 (3.1 mmol) was added to a solution of azomethine 1a-g
(3 mmol) in DMF (20 mL), and the reaction mixture was stirred at
r.t. until the reaction was complete (approx. 3-6 h, TLC). The solu-
tion was then poured into H2O (100 mL) and the solid was collected
by filtration and dried on air. In the case of azomethines 1a, e-g, the
corresponding azides 2a, e-g were formed, of which azides 2a, f
were recrystallised from MeCN and azides 2e, g were used without
further purification. In the case of azomethines 1b-d, indazoles
3b-d were formed. The isolation of indazoles was analogous to that
of azides.
Acknowledgement
We thank the International Science and Technology Center (Project
#419) for financial support.
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