Synthesis of 14π-electron peri-annelated tricyclic heteroaromatic systems based on 2,4,6-trinitrotoluene

Article abstract of DOI:10.1070/mc2002v012n05abeh001642

Methyl 1-aryl-7-nitro-1H-thiopyrano[4,3,2-cd]indazol-4-carboxylates 2 and 1,5-diaryl-7-nitro-1,5-dihydropyrazolo[3,4,5-de]-cinnolines 4 were prepared based on 1-aryl-3-formyl-4,6-dinitro-1H-indazoles 1, which were synthesised previously starting from 2,4,

Full text of DOI:10.1070/mc2002v012n05abeh001642

Mendeleev Commun., 2002, 12(5), 200–201
Synthesis of 14π-electron peri-annelated tricyclic heteroaromatic systems based on
2,4,6-trinitrotoluene
Aleksei M. Starosotnikov, Vasilii M. Vinogradov and Svyatoslav A. Shevelev*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328; e-mail: shevelev@mail.ioc.ac.ru
10.1070/MC2002v012n05ABEH001642
Methyl 1-aryl-7-nitro-1H-thiopyrano[4,3,2-cd]indazol-4-carboxylates 2 and 1,5-diaryl-7-nitro-1,5-dihydropyrazolo[3,4,5-de]-
cinnolines 4 were prepared based on 1-aryl-3-formyl-4,6-dinitro-1H-indazoles 1, which were synthesised previously starting from
2,4,6-trinitrotoluene.
Previously,1 we prepared 1-aryl-3-formyl-4,6-dinitroindazoles 1
starting from 2,4,6-trinitrotoluene (TNT). We found that the
CO2Me
O
action of anionic N-, O- and S-nucleophiles on compounds 1
under mild conditions resulted in selective substitution for the
nitro group at the 4-position. In this work, we used this property
of compounds 1 for the synthesis of 14π-electron peri-annelated
tricyclic heteroaromatic systems.
S
O
N
O2N
N
Ph
5a
NO2
CHO
i
CO2Me
CO2Me
N
O
S
S
O2N
N
ii
Ar
N
N
N
1a,b
O2N
O2N
N
a
Ar = Ph
b
Ar = 4-ClC6H4
Ph
Ph
iii
2a
6a
ii
i
CO2H
– NO2
S
CO2Me
NO2
NNHPh
S
N
CHO
O2N
N
N
N
Ph
O2N
O2N
N
N
7a
Ar
Ar
Scheme 2 Reagents and conditions: i, 35% H2O2 (8 equiv.), CF3COOH,
20 °C, 0.5 h; ii, 35% H2O2 (120 equiv.), AcOH, 60 °C, 12 h; iii, 10 equiv.
NaOH, H2O, 100 °C, 20 h.
3a,b
1'a,b
– H2O
iii
Thus, the interaction of formyldinitroindazoles 1a,b with the
methyl ester of thioglycolic acid in N-methylpyrrolidone or
DMF in the presence of solid K2CO3 resulted in peri-annelated
heterocyclic compounds, methyl 1-aryl-7-nitro-1H-thiopyrano-
[4,3,2-cd]indazol-4-carboxylates 2a,b (Scheme 1). It is believed
that 4-NO2 is initially replaced under the action of the
thioglycolate–K2CO3 system with the formation of product 1'.
This product undergoes the base-catalysed intramolecular con-
densation of the formyl group with the active methylene unit of
the SCH2CO2Me substituent (Scheme 1). Another reaction path,
precondensation at the methylene unit with the subsequent
intramolecular substitution for 4-NO2 under the action of the
condensation product, seems improbable because substitution for
4-NO2 in formyldinitroindazoles 1 under the action of aliphatic
thiols occurs in milder conditions (~20 °C) than the formation
of tricyclic compounds 2 (at 60 °C).
Under standard conditions, formyldinitroindazoles 1a,b form
phenylhydrazones 3a,b, which undergo intramolecular cycliza-
tion with substitution for 4-NO2 in N-methylpyrrolidone or
DMF in the presence of K2CO3 to give peri-annelated aromatic
heterocycles, 1,5-diaryl-7-nitro-1,5-dihydropyrazolo[3,4,5-de]-
cinnolines 4a,b. It is believed that the reaction occurs via the
deprotonation of phenylhydrazones with the formation of N-anions
3' (Scheme 1).
CO2Me
PhN
NO2
N
S
N
N
N
O2N
N
O2N
Ar
Ar
3'a b
,
2a,b
– NO2
Ph
N
N
N
O2N
N
Ar
4a,b
Scheme 1 Reagents and conditions: i, 1 equiv. HSCH2CO2Me, 2 equiv.
K2CO3, N-MP, 60 °C, 10 h; ii, 1 equiv. PhNHNH2·HCl, EtOH, 78 °C, 3 h;
iii, 1 equiv. K2CO3, N-MP, 80 °C, 10 h.
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Mendeleev Commun., 2002, 12(5), 200–201
Reactions of thiopyranoindazoles 2 were studied using tri-
This work was supported by the Russian Foundation for Basic
Research (grant no. 01-03-32261).
cyclic compound 2a as an example. Compound 2a was readily
and selectively oxidised with aqueous H2O2 in CF3COOH or
AcOH to sulfone 5a or sulfoxide 6a, respectively (Scheme 2).
The alkaline hydrolysis of compound 2a resulted in tricyclic
carboxylic acid 7a (Scheme 2).
References
1 V. M. Vinogradov, A. M. Starosotnikov and S. A. Shevelev, Mendeleev
Commun., 2002, 198.
Thus, starting from 1-aryl-3-formyl-4,6-dinitro-1H-indazoles
1, which in turn were prepared from TNT, we synthesised two
types of 14π-electron peri-annelated tricyclic heteroaromatic
systems: 1H-thiopyrano[4,3,2-cd]indazoles and 1,5-dihydro-
pyrazolo[3,4,5-de]cinnolines.
Note that 14π-electron peri-annelated heteroaromatic systems
containing two six-membered rings and one five-membered
ring are a rare type of heterocycles (e.g., see refs. 2, 3). As for
tricyclic systems prepared in this work, we failed to find pub-
lished procedures for the synthesis of such systems; only the
pharmacological properties of 1H-thiopyrano[4,3,2-cd]indazoles
with other substituents were reported previously.4
2 V. V. Mezheritskii and V. V. Tkachenko, in Adv. Heterocycl. Chem.,
1990, vol. 51, p. 1.
3 S. Tumkevicius, Liebigs Ann. Chem., 1995, 1703.
4 L. M. Werbel, E. F. Elslager and D. F. Worth, Adv. Pharmacol. Ther., Proc.
7th Int. Congr. Pharmacol., 1979, vol. 10, pp. 3–8 (Chem. Abstr., 1980,
92, 215).
The structure and composition of the prepared compounds
1
were supported by H NMR spectroscopy, electron-ionization
mass spectrometry (the formation of molecular ions was detected
in all cases), IR spectroscopy and elemental analysis.†
†
1H NMR spectra were measured on a Bruker AM-300 spectrometer
with TMS as a standard compound.
1
2a: 60% yield, mp 230–231 °C (CHCl3). H NMR (CDCl3) d: 4.0 (s,
3
3
3H, Me), 7.45 (t, 1H, Ph, JH–H 7.2 Hz), 7.6 (t, 2H, Ph, JH–H 7.2 Hz),
3
7.7 (s, 1H, Harom), 7.75 (d, 2H, Ph, JH–H 7.2 Hz), 7.95 (s, 1H, Harom),
8.15 (s, 1H, Harom).
2b: 77% yield, mp > 300 °C (CHCl3). 1H NMR (CDCl3) d: 3.95 (s, 3H,
Me), 7.55 (d, 2H, Harom, 3JH–H 8.8 Hz), 7.6 (d, 3H, Harom, 3JH–H 8.8 Hz),
7.95 (s, 1H, Harom), 8.1 (s, 1H, Harom).
3a: 74% yield, mp 260–261 °C. 1H NMR ([2H6]DMSO) d: 6.8 (t, 1H,
Ph), 7.0 (d, 2H, Ph), 7.2 (t, 2H, Ph), 7.6 (t, 1H, Ph), 7.7 (t, 2H, Ph), 7.85
(d, 2H, Ph), 8.2 (s, 1H, CH=N), 8.55 (s, 1H, Harom), 8.75 (s, 1H, Harom),
10.6 (s, 1H, NH).
3b: 61% yield, mp 267–269 °C. 1H NMR ([2H6]DMSO) d: 6.9 (m, 1H,
3
Ph), 7.1–7.3 (m, 4H, Ph), 7.7 (s, 1H, CH=N), 7.8 (d, 2H, Harom, JH–H
8.0 Hz), 8.05 (d, 2H, Harom, 3JH–H 8.0 Hz), 8.8 (s, 1H, Harom), 8.9 (s, 1H,
H
arom), 11.75 (s, 1H, NH).
4a: 47% yield, mp 257–259 °C. 1H NMR (CDCl3) d: 7.1 (s, 1H, Harom),
7.4–7.55 (m, 2H, Ph), 7.6–7.7 (m, 6H, Ph), 7.8 (d, 2H, Ph, 3JH–H 7.2 Hz),
7.9 (s, 1H, Harom), 8.1 (s, 1H, CH=N).
4b: 52% yield, mp 264–265 °C. 1H NMR ([2H6]DMSO) d: 6.95 (s,
1H, Harom), 7.5 (m, 1H, Ph), 7.6 (m, 6H, Ph), 8.9 (m, 3H, Ph, Harom), 8.2
(s, 1H, CH=N).
5a: 81% yield, mp 218–220 °C (CHCl3). 1H NMR ([2H6]DMSO) d:
4.0 (s, 3H, Me), 7.5–7.8 (m, 3H, Ph), 7.9 (d, 2H, Ph, 3JH–H 7.9 Hz), 8.55
(s, 1H, CH), 8.75 (s, 1H, Harom), 8.9 (s, 1H, Harom).
6a: 38% yield, mp 224–225 °C (CHCl3). 1H NMR ([2H6]DMSO) d:
4.0 (s, 3H, Me), 7.6–7.8 (m, 3H, Ph), 7.9 (d, 2H, Ph, 3JH–H 7.3 Hz), 8.05
(s, 1H, CH), 8.6 (s, 1H, Harom), 8.9 (s, 1H, Harom).
7a: 81% yield, mp 303–304 °C (CHCl3). 1H NMR ([2H6]DMSO) d:
7.45 (t, 1H, 3JH–H 6.7 Hz, Ph), 7.6 (t, 2H, Ph, 3JH–H 7.3 Hz, Ph), 7.8 (m,
3H, Ph, CH), 8.1 (s, 1H, Harom), 8.25 (s, 1H, Harom).
Received: 15th July 2002; Com. 02/1968
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