A straightforward synthesis of some fused aza-arenes via nucleophilic displacement of a ring hydrogen atom in nitroarenes by aromatic hydrazone anions

Article abstract of DOI:10.1039/b105230f

6-Nitroquinoline 6 undergoes direct cyclocondensation with aromatic aldehyde hydrazones 9 in the presence of sodium hydride in DMF at low temperature, giving the corresponding 3-aryl-1H-pyrazolo[3,4-f]quinolines 10 and/or 3-aryl[1,2,4]triazino[6,5-f]quino

Full text of DOI:10.1039/b105230f

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A straightforward synthesis of some fused aza-arenes via
nucleophilic displacement of a ring hydrogen atom in nitroarenes
by aromatic hydrazone anions
1
Koji Uehata, Takehiko Kawakami and Hitomi Suzuki*
Department of Chemistry, School of Science, Kwansei Gakuin University, Gakuen 2-1,
Sanda 669-1337, Japan. E-mail: hsuzuki@ksc.kwansei.ac.jp
Received (in Cambridge, UK) 14th June 2001, Accepted 2nd January 2002
First published as an Advance Article on the web 8th February 2002
6
-Nitroquinoline 6 undergoes direct cyclocondensation with aromatic aldehyde hydrazones 9 in the presence of
sodium hydride in DMF at low temperature, giving the corresponding 3-aryl-1H-pyrazolo[3,4-f ]quinolines 10 and/or
3
2
-aryl[1,2,4]triazino[6,5-f ]quinolines 11 in low to moderate yield. With aromatic keto hydrazones 7, 3,3-disubstituted
,3-dihydro[1,2,4]triazino[6,5-f ]quinoline-4-oxides 8 are obtained in moderate to good yield. The mode of cyclo-
condensation is considerably dependent on the electronic nature of a ring substituent of the aromatic hydrazones;
electron-donating substituents favor the formation of 11, while electron-withdrawing substituents work favorably for the
formation of 10. Monocyclic nitroarenes 15 react similarly with 4-nitrobenzaldehyde hydrazone 9a to give another
type of cyclocondensation product, 3-aryl-1H-indazoles 16, in moderate yield. In contrast, nucleophilic substitution
of a ring hydrogen atom takes place with 4-methylbenzaldehyde hydrazone 9f to yield N-arylated hydrazone 22b,
which, however, fails to cyclize to 16 under the conditions employed. The reaction has been suggested to proceed
through the initial attack of a hydrazone anion on the position adjacent to the nitro group, followed by migration of
2
an ipso hydrogen atom to the nitro group in the Meisenheimer intermediate 18. The resulting N -arylated hydrazone
anion would undergo ring closure via either addition to the nitroso group or displacement of this moiety, eventually
leading to the fused aza-arenes 8, 10/11, 13 or 16.
Introduction
triazine-5,7(6H,8H )-dione (fervenulin) 4 is a broad-spectrum
antibiotic isolated from natural source. 3-Methoxy-2-methyl-
6
Fused [1,2,4]triazines are important as the basic framework for
a variety of pharmaceuticals and agrochemicals. Representative
examples are shown in Chart 1, where 3-aminobenzo[1,2,4]-
triazine 1,4-dioxide 1 (SR4233) received considerable attention
as a new class of anti-tumor agent owing to its selective toxicity
toward hypoxic cells both in vitro and in vivo. The mechanism
of DNA cleavage by this type of compound is of biochemical
and pharmaceutical interest. 7-Chloro-3-aminobenzo[1,2,4]-
triazine 1-oxide 2 is long known for its activity as antimalarial,
2
H-pyrazolo[4,3-e][1,2,4]triazine 5 is a red pigment of a unique
7
chromophore produced by a microorganism. Although a few
methods are available in the literature for the construction of
this type of polycondensed aza-arenes, most of them involve a
8
multi-step procedure starting from inconvenient materials.
1,2
We have recently reported that a strong base such as sodium
hydride can promote the displacement of a ring hydrogen atom
of nitroarenes by nucleophiles, providing a straightforward
route to a variety of functionalized arenes. Typical examples are
3
4
while 3-dimethylamino-4H-[1,2,4]triazino[5,6-b]indazole
exhibits a herbicidal effect. 6,8-Dimethylpyrimido[5,4-e][1,2,4]-
3
shown in Scheme 1, taking 6-nitroquinoline 6 as the common
5
9–14
substrate.
As part of our ongoing programme, we have
extended this new type of aromatic nucleophilic substitution to
the single-step construction of the pyrazolo[3,4-f ]quinoline
and [1,2,4]triazino[6,5-f ]quinoline structures 10 and 11.
Results and discussion
Reaction of 6-nitroquinoline with aromatic hydrazone anions
When 6-nitroquinoline 6 was treated with benzophenone hydra-
zone 7a in the presence of sodium hydride (NaH) in N,N-di-
methylformamide (DMF) at low temperature, a new type of
cyclocondensation took place to produce 3,3-diphenyl-2,3-
dihydro[1,2,4]triazino[6,5-f ]quinoline 4-oxide 8a in a moderate
yield (Scheme 2). Best results were obtained when nitroarene 6
and hydrazone 7a were treated in a 1 : 1 molar ratio in the
presence of 4 equiv. of NaH (Table 1, Entry 6). Considerable
amounts of undefined polar by-products accompanied the
reaction, but they were easily removed by simple filtration over
a thin bed of silica gel. Elevated temperature promoted side
reactions and resulted in a diminished yield of 8a. When a
t
weaker base such as BuOK or LiH was used, compound 8a
Chart 1
could not be obtained. The use of N-methylpyrrolidin-2-one
6
96
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b105230f

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a
Table 1 Reaction of 6-nitroquinoline 6 with benzophenone hydrazone 7a
b
Entry
7a (equiv)
NaH (equiv)
Temp. (ЊC)
Solvent
Yields of 8a (%)
1
2
1
1
1
1
2
1
2
1
2
1
4
4
4
8
4
4
4
4
4
4
rt
rt
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
NMP
THF
17
3
c
d
3
4
5
6
7
8
9
Ϫ25
Ϫ25
Ϫ25
Ϫ10
Ϫ10
Ϫ10
Ϫ10
Ϫ10
32e
38f
35
g
61 (59)g
60 (53)
14
15
35
1
0
a
b
c
All reactions were carried out in a given solvent (15 mL) for 24 h, unless otherwise stated. HPLC yield. To a DMF solution (5 mL) of 6 was added
d
e
dropwise a solution of 7a in the same solvent (10 mL) during 5 h. Substrate 6 was recovered in 13, 3 and 2% yield, respectively. Substrate 6 was
f
g
recovered in 13, 3 and 2% yield, respectively. Substrate 6 was recovered in 13, 3 and 2% yield, respectively. Numeral in parenthesis refers to isolated
yield.
Table 2 Reaction of 6-nitroquinoline 6 with benzaldehyde hydrazones
9
a–g
a
Yield (%)
Hydrazone
10
11
9
9
9
9
9
9
9
a
b
c
d
e
f
50
trace
6
—
—
—
—
—
19
27
24
16
28
24
b
g
a
b
Isolated yield. Detected by NMR.
9
Scheme 1 Reagents and conditions: a) Me SiCF , KF, DMF, ; b)
3
3
1
0
t
11
MeCN, NaOEt, DMF; c) MeNO , Bu OLi, DMF; d) Guanidine,
2
t
12
13
14
Bu OK, THF; e) KOR, THF; f ) RSH, NaH, THF.
Scheme 3
electronic nature of a ring substituent on the aromatic hydra-
zones 9. Electron-donating groups such as methyl and methoxy
favored the ring closure with a nitrogen atom of the nitro group
of 6 to afford the [1,2,4]triazino[6,5-f ]quinoline ring system
Scheme 2
1
1d–g, while the electron-withdrawing nitro group led to the
(
NMP) or tetrahydrofuran (THF) as the solvent gave less satis-
ring closure involving replacement of the nitro group of 6, pro-
ducing the pyrazolo[3,4-f ]quinoline ring system 10a. With the
inductively positive to electron-withdrawing but mesomerically
negative to electron-donating 4-chlorine substituent, both types
of cyclocondensation took place in parallel to yield aza-arenes
10c and 11c, the latter predominating in amount over the
former (Table 2). With the fluorine substituent, however, com-
pound 11b was much preferred. The reason is not clear. Both
types of product were readily separated by chromatography on
silica gel using a mixture of hexane and EtOAc as the eluting
solvent. Unfortunately, all attempts to improve the product
yield have failed; a different combination of base and solvent as
factory results (Table 1, Entries 8–10). To our knowledge, this
type of cyclocondensation between nitroarenes and hydrazones
has not previously been reported. Therefore, the use of the
hydrazone anion as an ambident C,N-nucleophile may provide
an attractive new tool for the single-step construction of multi-
functionalized aza-arene structures.
6
-Nitroquinoline 6 reacted with benzaldehyde hydrazones
a–g under similar conditions to afford 3-aryl-1H-pyrazolo[3,4-
f ]quinolines 10 and/or 3-aryl [1,2,4]triazino[6,5-f ]quinolines
1 (Scheme 3). The results are listed in Table 2. The mode of
cyclocondensation was found to depend considerably on the
9
1
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702
697

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Table 4 Reaction of monocyclic nitroarenes 15 with hydrazones 9
Table 3 Reaction of 6-nitroquinoline 6 with hydrazones 12a–d
a
a
Yield (%)
Nitroarene
Hydrazone
Temp.(ЊC)
Yield of 16 (%)
Hydrazone
13
14
1
1
1
5a R = 3-NO
9a
9a
9a
9f
Ϫ10
rt
rt
rt
Ϫ10
Ϫ10
37
21 (35)
36
2
1
b, c
5b R = 4-Cl
1
1
1
1
1
2a
2b
2c
2d
26
13
35
—
—
—
—
13
15c R = 4-NO
2
1
d
15a R = 3-NO
—e
2
1
15b R = 4-Cl
9f
—
1
f
15c R = 4-NO
9f
—
2
a
a
b
c
Isolated yield.
Isolated yield. Starting material was recovered in (40%). Numeral in
d
2
parenthesis refers to conversion. N -(2, 4-dinitrophenyl)hydrazone
e
f
2
2a was obtained. Dehalogenation product was obtained. Denitra-
well as a prolonged reaction time proved to be fruitless. Since
benzaldehyde hydrazones were partly lost as the corresponding
azines under the conditions employed, this may also have
caused the diminished yield.
tion product was obtained.
When compound 6 was treated with hydrazones 12a–d
bearing a substituent on the terminal nitrogen atom, different
results ensued (Scheme 4; Table 3). When a nitro group was
Scheme 5
Scheme 4
zone 9f resulted in the displacement of a ring hydrogen atom
at the 4-position by the hydrazone anion, giving the N -(2,4-
2
present on the aromatic ring of the hydrazone, the cyclization
involving the replacement of the nitro group of 6 took place
to give pyrazolo[3,4-f ]quinolines 13a,b. In contrast, when the
corresponding substituent is a methyl group, compound 6
simply underwent nucleophilic displacement of a ring hydrogen
atom at 5-position by the hydrazone anion to yield N-arylated
hydrazone 14. Interestingly, when a phenyl group was present
on the terminal nitrogen atom of the hydrazone, ring closure
took place again via the replacement of the nitro group to
afford the corresponding 3-arylpyrazolo[3,4-f ]quinoline 13b,c,
irrespective of the electronic nature of the ring substituent
groups on the hydrazone.
dinitrophenyl) derivative 22a of the original hydrazone as the
main product.
Copper salts are known to catalyze the addition of O-methyl-
hydroxylamine to nitroarenes. Thus, Seko et al. carried out
the reaction of nitroarenes with O-alkylhydroxylamines in the
presence of some copper catalyst and obtained the correspond-
15
ing nitroanilines in high yield. In the hope of similar catalysis,
nitroarene 6 was treated with the anion of 9f in the presence
of several metal salts such as CuCl, CuCl or ZnCl . To our
2
2
disappointment, however, only nucleophilic displacement of
a hydrogen atom took place at the 5 position of 6, giving
N-nitroaryl derivative 17 of the original hydrazone as the sole
main product (Scheme 6). Little or no cyclocondensation
Reaction of monocyclic nitroarenes with aromatic hydrazones
When substituted nitrobenzenes 15 were similarly treated with
aromatic hydrazones 9, a different type of cyclocondensation
took place to produce 3-arylindazoles 16, though the yield of
the products was not satisfactory (Scheme 5; Table 4). Thus,
1
,3-dinitrobenzene 15a underwent cyclocondensation with 4-
nitrobenzaldehyde hydrazone 9a via the replacement of the
nitro group of 15a, giving 5-nitro-3-(4-nitrophenyl)indazole 16a
as the sole product in 37% isolated yield. A similar reaction of
4
-chloronitrobenzene 15b led to 6-chloro-3-(4-nitrophenyl)-
indazole 16b in 21% isolated yield. Interestingly enough, the
chlorine atom remained intact despite of its presence at the
most activated position of the substrate. In contrast, when 4-
methylbenzaldehyde hydrazone 9f was employed as the nucleo-
phile, preferential displacement of the chlorine atom took place
and no cyclocondensation product was obtained. A similar
attempt to cyclocondense 1,3-dinitrobenzene 15a with hydra-
Scheme 6
product was obtained under these conditions (Table 5). All
attempts to cyclize 17 with sodium hydride in DMF failed, thus
ruling out the possible role of this hydrazone as an intermediate
to the triazino[6,5-f ]quinoline 11f.
6
98
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702

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Table 5 Reaction of 6-nitroquinoline 6 with hydrazone 9f in the pres-
ence of metal salt
a
Yield (%)
Metal salt
Time (t/h)
11f
17
b
CuCl
CuCl2
ZnCl2
PdCl2
3
3
6
3
trace
3
—
14
6
12c
—
—
a
b
c
Isolated yield. Detected by NMR. A tarry material was obtained.
Table 6 The reaction of 6-nitroquinoline 6 with hydrazones 7a–e
Hydrazone
a, b
R
Ar
Yield of 8 (%)
7a
7b
7c
7d
7e
C H5
4-MeC H
Me
Me
Me
C H
4-MeC H
59
6
6
5
48 (51)
61 (68)
63 (70)
63 (68)
6
4
6
4
4
C H
6
5
4-MeC H
4-BrC H
6
6
4
a
b
Isolated yield. Numeral in parenthesis refers to conversion.
Possible reaction mechanism
Although the mechanism for the formation of compounds 10
and 11 is not clear at present, a possible reaction sequence is
outlined in Scheme 7. In the initial stage, the hydrazone anion
attacks the 5-position of 6-nitroquinoline 6 to form a Meisen-
16,17
heimer intermediate 18.
This intermediate anion undergoes
the nitro–aci-nitro isomerization followed by dehydration to
18
form the anion 19, which then would cyclize via two com-
peting pathways depending on the electronic nature of the ring
substituent group of the original chemical aromatic hydrazone.
When the substituent is electron-withdrawing, such as nitro,
the hydrazone anion is stabilized and undergoes an ordinary
addition–elimination sequence to displace the NO moiety (path
19
a). On the other hand, electron-releasing substituent groups
such as methyl and methoxy destabilize the anion by increasing
the electron density at the anionic center, which will be readily
trapped by the nearby nitroso group to form the triazino-
[6,5-f ]quinoline structure 8 or 11 (path b). The reduction of
the nitro group to a nitroso group has often been observed in
the strong-base-assisted nucleophilic aromatic substitution of
20,21
nitroarenes.
Due to steric bulkiness, the hydrazone anion
generated from keto hydrazones 7 undergoes exclusive ring
closure with the nitroso group. Thus, the reaction of 6 and 7
under similar conditions produces triazino[6,5-f ]quinoline
oxides 8 in good yield (Table 6).
The formation of 3-arylated indazoles 16 is somewhat tricky
to explain. We depict a possible route from 15b to 16b in
Scheme 8. Nitroarene 15b reacts with a benzaldehyde hydrazone
anion to form a Meisenheimer intermediate 20 via the kinetic-
ally controlled addition of the anion to a position adjacent to
the nitro group in 15b. The electron-withdrawing nitro group of
Scheme 7
quinoline, and indazole frameworks, which is based on the
direct cyclocondensation of nitroarenes with aromatic hydra-
zones in the presence of sodium hydride. It can be carried out
under mild conditions using readily accessible or commercially
available inexpensive materials. The yields of the products are
moderate, but this disadvantage would be compensated for by
readily accessible starting materials, simple manipulation,
economy, a one-pot procedure, and mild conditions.
9
a would facilitate the generation and attack of the hydrazone
anion, resulting in the formation of the indazole 16b via the
displacement of the nitro group (path c). On the other hand,
the electron-donating methyl group in 9f does not stabilize the
hydrazone anion and consequently the Meisenheimer inter-
2
mediate 21 is reluctant to cyclize and eventually leads to N -
Experimental
arylated hydrazone 22b (path d).
Melting points were determined on a Yanaco MP S3 apparatus
1
13
and are uncorrected. H and C NMR spectra were recorded in
Conclusions
CDCl and/or DMSO-d on a JEOL JNM-A400 NMR spectro-
3
6
We have developed a new, straightforward method for the con-
meter using tetramethylsilane as internal reference, unless
struction of the [1,2,4]triazino[6,5-f ]quinoline, pyrazolo[3,4-f ]-
otherwise mentioned. J-values are given in Hz. IR measure-
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702
699

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Ϫ1
(
31); νmax (KBr)/cm 3484br, 3183, 2923, 1447, 1235, 1084, 691
(
Found: C, 73.58; H, 5.02; N, 14.63. C H N Oؒ1/2EtOH
22
16
4
requires C, 73.58; H, 5.10; N, 14.92%.)
3
,3-Bis-(4-methylphenyl)-2,3-dihydro[1,2,4]triazino[6,5-f ]-
quinoline 4-oxide 8b. Mp 135–137 ЊC; δH (CDCl ) 2.35 (s, 6H),
3
7
6
.17 (d, 4H, J = 7.8), 7.22 (dd, 1H, J = 4.6, 8.1), 7.24–7.31 (m,
H), 7.63 (d, 1H, J = 10.0), 8.30 (d, 1H, J = 4.6), 8.60 (d, 1H,
J = 8.1); δ (CDCl ) 21.2, 21.7, 23.7, 116.7, 120.8, 122.0, 122.6,
C
3
1
1
27.9 (2C), 128.6 (4C), 129.0 (4C), 132.7 (2C), 140.0, 141.1,
ϩ
48.5, 150.0, 150.7; m/z (EI) 349 (5%), 334 (M Ϫ 46, 68), 319
Ϫ1
(
95), 159 (100); νmax (KBr)/cm 3491 br(NH), 1512, 1445, 1373,
1
227, 1179, 1074, 1059, 1032, 856, 801, 762, 681, 550 (Found:
C, 75.74; H, 5.36; N, 14.63. C H N O requires C, 75.77; H,
24
20
4
5
.30; N, 14.73%).
3
-Methyl-3-phenyl-2,3-dihydro[1,2,4]triazino[6,5-f ]quinoline
4
-oxide 8c. Mp 121–123 ЊC; δH (DMSO-d ) 1.90 (s, 3H), 7.22–
6
7
.37 (m, 7H), 7.53 (d, 1H, J = 10.0), 8.24 (d, 1H, J = 7.6), 8.59
(
d, 1H, J = 4.4), 10.49 (s, 1H); δC (CDCl ) 23.9, 80.8, 120.4,
3
1
1
22.5, 125.0 (2C), 126.4, 128.5 (2C), 128.9, 130.4, 130.8, 132.6,
ϩ
35.2, 138.1, 148.7, 149.8; m/z (CI) 245 (M Ϫ 45, 100%), 246
Ϫ1
(
36), 244 (14), 120 (6) νmax (KBr)/cm 3187 br(NH), 1466,
1
7
445, 1400, 1368, 1254, 1084, 997, 826, 764, 702 (Found: C,
0.14; H, 4.90; N, 19.25. C H N O requires C, 70.33; H, 4.86;
Scheme 8
17
14
4
N, 19.30%).
ments were made on a JEOL FTIR-5300 spectrophotometer
for KBr pellets and only prominent peaks in the region 2000–
Ϫ1
3
-Methyl-3-(4-methylphenyl)-2,3-dihydro[1,2,4]triazino[6,5-
7
7
00 cm were recorded. CI mass spectra were determined at
0 eV on a Shimadzu GCMS-QP5000 mass spectrometer using
f ]quinoline 4-oxide 8d. Mp 123–125 ЊC; δH (DMSO-d ) 1.87
6
(
7
s, 3H), 2.18 (s, 3H), 7.09 (d, 2H, J = 8.0), 7.20–7.30 (m, 3H),
.35 (dd, 1H, J = 4.8, 7.6), 7.51 (d, 1H, J = 10.0), 8.23 (d, 1H,
J = 7.6), 8.59 (d, 1H, J = 4.8), 10.44 (s, 1H); δ (CDCl ) 20.9,
isobutane as ionizing gas. All reagents excepting hydrazones
were reagent-grade commercial products and used as received.
DMF was distilled from CaH prior to use. Progress of the
C
3
2
2
1
(
3
6
3.8, 80.7, 120.4, 122.5, 125.0 (2C), 126.4, 129.1 (2C), 130.3,
reaction was monitored by thin-layer chromatography (TLC)
on a glass plate coated with silica gel 60 F254 (Merck). Prepara-
tive chromatography was performed on a column packed with
Merck Silica Gel (230–400 mesh), using a mixture of EtOAc
and hexane as the eluent. Gradient HPLC was carried out on a
Shimadzu LC-10 apparatus using a mixture of methanol and
water. Microanalyses were performed at Advanced Instru-
mentation Center, Ehime University. [1,2,4]Triazino[6,5-f ]-
quinolines 8 and 11 and pyrazolo[3,4-f ]quinolines 10 are poorly
soluble in common organic solvents and were recrystallized
from EtOH–dichloromethane or pyridine. With some com-
pounds, small amounts of solvent were strongly retained in
crystals and could not be removed even after drying under
vacuum.
30.6, 132.7, 135.0, 135.1, 138.8, 148.8, 149.8; m/z (CI) 259
ϩ
Ϫ1
M Ϫ 45, 100%), 258 (18), 216 (5), 160 (17); ν (KBr)/cm
max
264 br(NH), 1512, 1465, 1445, 1370, 1246, 1208, 1082, 812,
87, 592, 473 (Found: C, 70.82; H, 5.59; N, 18.05. C H N O
requires C, 71.04; H, 5.30; N, 18.41%).
18 16
4
3-(4-Bromophenyl)-3-methyl-2,3-dihydro[1,2,4]triazino[6,5-
f ]quinoline 4-oxide 8e. Mp 133–134 ЊC; δ (DMSO-d ) 1.89
(s, 3H), 7.25 (d, 1H, J = 10.0), 7.28 (d, 2H, J = 6.8), 7.37 (dd, 1H,
J = 4.8, 7.6), 7.50–7.53 (m, 3H), 8.24 (d, 1H, J = 7.6), 8.61 (d,
1H, J = 4.8), 10.51 (s, 1H); δ (CDCl ) 9.7, 117.1, 122.9 (2C),
126.4, 126.8, 128.5, 128.6, 129.1, 129.3, 131.8, 132.0, 133.3
H
6
C 3
ϩ
(2C), 137.2, 143.7, 151.0; m/z (CI) 325 (M Ϫ 44, 100%), 324
ϩ
ϩ
Ϫ1
(
M Ϫ 45, 37), 323 (M Ϫ 46, 73); ν (KBr)/cm 3192 (NH),
max
Synthesis of 3,3-disubstituted 2,3-dihydro[1,2,4]triazino[6,5-f ]-
quinoline 4-oxides 8a–e. Typical procedure
1514, 1466, 1399, 1368, 1254, 1084, 1009, 826, 806 (Found:
C, 54.87; H, 3.64; N, 14.91. C17 O requires C, 55.30; H,
.55; N, 15.17%).
H
13BrN
4
3
A mixture of 6-nitroquinoline 6 (0.30 g, 1.7 mmol), NaH
(
0.29 g, 7.0 mmol) and DMF (15 mL) was cooled to Ϫ10 ЊC and
Synthesis of 3-aryl-1H-pyrazolo[3,4-f ]quinolines 10a–c/13a–c
and 3-aryl[1,2,4]triazino[6,5-f ]quinolines 11b–g. Typical
procedure
benzophenone hydrazone 7a (0.40 g, 2.0 mmol) was added
in one portion. The resulting dark red solution was stirred at
this temperature for 24 h and then diluted with water (50 mL).
The organic phase was collected with EtOAc (50 mL × 3),
dried over anhydrous MgSO , and evaporated under reduced
pressure. The residue was chromatographed on silica gel using
a mixture of EtOAc and hexane (1 : 3 to 1 : 1) to give the
A suspension of NaH (0.29 g, 7.0 mmol) in DMF (15 mL) was
cooled to Ϫ10 ЊC and 6-nitroquinoline 6 (0.30 g, 1.7 mmol)
followed by 4-chlorobenzaldehyde hydrazone 9c (0.31 g,
2.0 mmol) were added. The resulting dark red solution was
stirred at this temperature for 24 h and then diluted with water
(50 mL). The aqueous phase was extracted with EtOAc (50 mL
× 3) and the combined extracts were dried over anhydrous
4
[1,2,4]triazino[6,5-f ]quinoline-4-oxide 8a as an orange-colored
solid (0.35 g, 59%), which was recrystallized from ethanol to
give crystalline 8a as an ethanol solvate.
MgSO . The solvent was removed under reduced pressure and
4
3
,3-Diphenyl-2,3-dihydro[1,2,4]triazino[6,5-f ]quinoline
4-
the residue was chromatographed on silica gel using a mixture
of EtOAc and hexane (1 : 3 to 1 : 1) to elute 3-(4-chlorophenyl)-
1H-pyrazolo[3,4-f ]quinoline 10c (0.028 g, 6%) and 3-(4-chloro-
phenyl)[1,2,4]triazino[6,5-f ]quinoline 11c (0.13 g, 27%) in that
order.
oxide 8a. Mp 136–137 ЊC; δ (DMSO-d ) 7.27 (d, 1H, J = 10.0),
H
6
7
(
1
.32–7.34 (m, 3H), 7.37 (dd, 1H, J = 4.6, 8.1), 7.40–7.56
m, 8H), 8.26 (dd, 1H, J = 1.7, 4.6), 8.26 (dd, 1H, J = 1.7, 8.1),
0.45 (s, 1H); δC (DMSO-d ) 86.1, 120.1, 123.1, 126.0, 128.1
6
(
(
4C), 128.4 (4C), 129.2 (2C), 129.6, 130.9, 132.5, 132.7, 136.4
2C), 147.8, 149.9; m/z (CI) 339 (5.4%), 307 (M Ϫ 45, 100), 182
Other 3-aryl-1H-pyrazolo[3,4-f ]quinolines 10/13 and 3-aryl-
[1,2,4]triazino[6,5-f ]quinolines were obtained similarly.
ϩ
7
00
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702

View Online
3
-(4-Nitrophenyl)-1H-pyrazolo[3,4-f ]quinoline 10a. Mp 281–
J = 4.4, 8.4), 8.15 (d, 1H, J = 9.2), 8.50 (d, 1H, J = 9.2), 8.75 (d,
2H, J = 8.0), 9.18 (dd, 1H, J = 1.6, 8.4), 9.77 (dd, 1H, J = 1.6,
2
8
1
(
1
82 ЊC; δ (DMSO-d ) 7.51 (dd, 1H, J = 4.0), 7.96–7.99 (m, 2H),
.04 (d, 2H, J = 8.0), 8.39–8.44 (m, 3H), 8.83 (d, 1H, J = 4.4),
4.03 (s, 1H); δ (DMSO-d ) 113.8, 115.2, 121.8, 122.0, 123.9
2C), 129.5, 129.8, 130.4 (2C), 139.3, 141.4, 144.8, 145.8,
47.3, 147.9; m/z (CI) 290 (M ϩ 1, 100%), 244 (39), 190 (51);
H
6
8.4); δ (CDCl ) 123.1, 123.2, 123.9, 124.3, 128.2 (2C), 128.9,
C
3
129.3, 130.0 (2C), 130.5, 130.8, 132.0, 138.2, 139.7, 153.0;
C
6
ϩ
ϩ
m/z (CI) 295 (M ϩ 2, 3.3%), 293 (M , 10.7) 266 (27), 264 (82),
ϩ
Ϫ1
132 (34), 127 (100); νmax (KBr)/cm 1561, 1381, 1343, 1263,
Ϫ1
νmax (KBr)/cm 3110 br(NH), 1601, 1545, 1516, 1350, 968, 855,
1090, 1067, 1015, 835, 810, 785, 409. This compound was
8
08 (Found: C, 65.82; H, 3.76; N, 18.94. C H N O requires C,
difficult to obtain in a form completely free from 10c.
16
10
4
2
6
6.20; H, 3.47; N, 19.30%).
3
-Phenyl[1,2,4]triazino[6,5-f ]quinoline 11d. Mp 178–179 ЊC;
3
-(4-Fluorophenyl)-1H-pyrazolo[3,4-f ]quinoline 10b. δ (CD-
δ
H
(CDCl ) 7.55–7.65 (m, 3H), 7.81 (dd, 1H, J = 4.4, 8.4),
3
H
Cl ) 7.06 (d, 1H, J = 9.6), 7.10 (d, 2H, J = 9.2), 7.41 (dd, 1H,
8.44 (d, 1H, J = 10.0), 8.62 (dd, 2H, J = 1.6, 7.2), 8.67 (dd, 1H,
J = 10.0), 9.19 (dd, 1H, J = 1.6, 4.4), 9.69 (dd, 1H, J = 1.6, 8.4);
3
J = 4.2, 9.2), 7.46 (d, 1H, J = 9.6), 7.66 (d, 2H, J = 9.2), 8.32 (d,
H, J = 9.2), 8.93 (d, 1H, J = 4.2), 12.48 (s, 1H). This compound
was difficult to obtain in a form completely free from 11b.
1
δ
C
(DMSO-d
6
) 123.5, 124.4, 128.0 (2C), 128.5 (2C), 129.0,
131.0, 131.2, 134.7, 139.1, 141.9, 143.5, 148.0, 152.4, 160.9;
m/z (CI) 259 (M ϩ 1, 100%), 149 (27); ν (KBr)/cm 1583,
ϩ
Ϫ1
max
3
-(4-Chlorophenyl)-1H-pyrazolo[3,4-f ]quinoline 10c. Mp
1516, 1435, 1389, 1345, 1277, 1196, 1053, 1022, 855, 804, 748,
2
3
62–263 ЊC; δH (DMSO-d ) 7.48–7.53 (m, 3H), 7.60–7.67 (m,
H), 8.03 (d, 1H, J = 9.2), 8.99 (d, 1H, J = 4.3), 9.15 (d, 1H,
J = 8.8), 11.66 (s, 1H); m/z (CI) 281 (M ϩ 2, 12%), 279 (M ,
9), 277 (85), 140 (100). This compound was difficult to obtain
in a form completely free from 11c.
694, 550 (Found: C, 73.88; H, 4.02; N, 21.48. C16H N requires
10 4
6
C, 74.40; H, 3.90; N, 21.69%).
ϩ
ϩ
3
-(3-Methylphenyl)[1,2,4]triazino[6,5-f ]quinoline 11e. Mp
5
1
78–180 ЊC; δ (CDCl ) 2.54 (s, 3H), 7.43 (d, 1H, J = 7.2), 7.51
H
3
(
t, 1H, J = 7.2), 7.82 (dd, 1H, J = 4.4, 8.2), 8.16 (d, 1H, J = 9.6),
8
9
1
1
.49 (d, 1H, J = 9.6), 8.61 (m, 2H), 9.17 (dd, 1H, J = 1.6, 4.4),
1
-Methyl-3-(4-nitrophenyl)-1H-pyrazolo[3,4-f ]quinoline 13a.
.78 (dd, 1H, J = 1.6, 8.2); δ (CDCl ) 24.6, 117.7, 119.9, 124.3,
Mp 291–293 ЊC; δ (CDCl ) 4.26 (s, 3H), 7.39 (dd, 1H, J = 4.0,
.0), 7.78 (d, 1H, J = 9.2), 7.97 (d, 2H, J = 8.8), 8.08 (d, 1H,
J = 9.2), 8.43 (m, 3H), 8.88 (d, 1H, J = 4.0); δ (CDCl ) 36.18,
08.9, 113.5, 121.7, 124.1 (2C), 130.2 (2C), 130.4, 135.2, 139.3,
41.3, 144.2, 146.2, 147.9, 148.2, 148.3; m/z (EI) 304 (M ,
00%), 303 (12), 257 (16), 243 (17), 231 (8), 214 (14), 203 (8);
νmax (KBr)/cm 1599, 1514, 1346, 1146, 1105, 972, 808 (Found:
C, 67.23; H, 4.04; N, 18.14. C H N O requires C, 67.10; H,
C
3
H
3
25.9, 129.9, 131.9, 132.6, 134.6, 135.2, 139.0, 142.7, 143.9,
8
ϩ
48.6, 152.8, 162.1, 168.3; m/z (CI) 273 (M ϩ 1, 100%), 244
C
3
Ϫ1
(
5), 117 (6); νmax (KBr)/cm 1591, 1514, 1462, 1389, 1343, 1296,
1
1
1
ϩ
1
240, 1181, 1152, 1057, 806, 775, 696 (Found: C, 74.84; H, 4.50;
N, 20.46. C H N requires C, 74.98; H, 4.44; N, 20.58%).
17 12
4
Ϫ1
3
-(4-Methylphenyl)[1,2,4]triazino[6,5-f ]quinoline 11f. Mp
17
12
4
2
1
99–201 ЊC; δ (CDCl ) 2.50 (s, 3H), 7.43 (d, 2H, J = 8.2), 7.81
3
.97; N, 18.41%).
H
3
(
8
dd, 1H, J = 4.4, 8.4), 8.15 (d, 1H, J = 9.0), 8.48 (d, 1H, J = 9.0),
.69 (d, 2H, J = 8.2), 9.16 (dd, 1H, J = 1.6, 4.4), 9.77 (dd, 1H,
J = 1.6, 8.4); δ (CDCl ) 21.6, 118.5, 122.3, 122.9, 123.2, 128.5,
3
-(4-Nitrophenyl)-1-phenyl-1H-pyrazolo[3,4-f ]quinoline 13b.
Mp 213–214 ЊC; δ (CDCl ) 7.42 (dd, 1H, J = 4.4, 8.8), 7.51 (t,
H, J = 7.4), 7.63 (t, 2H, J = 7.4), 7.79 (d, 2H, J = 7.6), 8.01–8.12
m, 4H), 8.40–8.47 (m, 3H), 8.91, (d, 1H, J = 4.4); δ (CDCl )
14.7, 116.6, 121.8, 122.7, 124.01 (2C), 124.03 (2C), 128.2,
29.7 (2C), 130.3, 130.5 (2C), 130.9, 138.5, 139.0, 140.9, 146.1,
46.5, 148.1, 148.6; m/z (EI) 366 (M , 100%), 365 (11), 319 (29),
59 (32); νmax (KBr)/cm 1599, 1522, 1348, 1136, 968, 856 810,
56, 694; (Found: C, 71.74; H, 4.05; N, 15.05. C H N O
requires C, 72.12; H, 3.85; N, 15.29%).
C
3
H
3
1
1
28.7 (2C), 129.5 (2C), 132.5, 135.3, 139.5, 142.2, 149.3, 154.0,
56.8; m/z (CI) 273 (M ϩ1, 100%), 245 (2), 136 (4), 135 (4);
1
(
1
1
1
1
7
ϩ
C
3
Ϫ1
νmax (KBr)/cm 1609, 1580, 1507, 1427, 1397, 1345, 1317, 1263,
1
188, 1065, 847, 818, 542 (Found: C, 74.85; H, 4.50; N, 20.45.
ϩ
C H N requires C, 74.98; H, 4.44; N, 20.58%).
17 12
4
Ϫ1
3
-(4-Methoxyphenyl)[1,2,4]triazino[6,5-f ]quinoline 11g. Mp
22
14
4
2
2
7
8
37–238 ЊC; δH (DMSO-d ) 3.80 (s, 3H), 7.02 (d, 2H, J = 8.8),
.44 (d, 1H, J = 9.4), 7.61 (d, 2H, J = 8.8), 7.65 (dd, 1H, J = 3.8,
.8), 8.07 (d, 1H, J = 9.4), 9.00 (d, 1H, J = 3.8), 9.32 (d, 1H,
6
3
-(4-Methylphenyl)-1-phenyl-1H-pyrazolo[3,4-f ]quinoline
J = 8.8); δ (CDCl ) 55.4, 114.2 (2C), 114.6, 120.1, 121.0, 125.1,
C
3
1
3c. Mp 206–207 ЊC; δH (CDCl ) 2.50 (s, 3H), 7.35 (dd, 1H,
J = 4.4, 8.5), 7.39 (d, 2H, J = 8.0), 7.52 (m, 3H), 7.70 (d, 2H,
J = 8.0), 7.80 (dd, 2H, J = 1.5, 7.3), 8.01 (d, 1H, J = 9.5), 8.06
d, 1H, J = 9.52), 8.54 (d, 1H, J = 8.5), 8.85 (d, 1H, J = 4.4);
δ (CDCl ) 21.5, 114.7, 116.8, 121.5, 123.4, 123.9 (2C), 127.6,
29.4 (2C), 129.5 (2C), 129.6 (2C), 130.3, 130.8, 131.1, 138.0,
38.7, 139.4, 146.3, 148.1, 148.6; m/z (EI) 335 (M , 100%), 334
49), 319 (8), 167 (23); νmax (KBr)/cm 1597, 1522, 1503, 1393,
134, 965, 808, 770, 694 (Found: C, 82.30; H, 5.25; N, 12.57.
3
1
27.0, 129.0, 130.1 (2C), 132.1, 139.1, 147.4, 153.2, 161.0, 162.0;
ϩ
m/z (CI) 289 (M ϩ 1, 100%), 263 (14), 190 (32), 136 (41);
νmax (KBr)/cm 1603, 1507, 1474, 1432, 1406, 1333, 1229, 1254,
Ϫ1
(
1
177, 1026, 831, 540, 442. This compound crystallized from
C
3
EtOH–dichloromethane as fine plates, which retained part of
the solvent even after drying under vacuum over CaCl2.
1
1
(
ϩ
Ϫ1
2
Synthesis of N -(nitroaryl) derivatives of 4-methylbenzaldehyde
hydrazones 9f and 12d. Typical procedure
1
C H N requires C, 82.36; H, 5.11; N, 12.53%).
2
3
17
3
To a mixture of 6-nitroquinoline 6 (0.30 g, 1.7 mmol), NaH
(0.29 g, 7.0 mmol) and DMF (15 mL) cooled to Ϫ10 ЊC were
added 4-methylbenzaldehyde hydrazone 9f (0.27 g, 2.0 mmol)
and CuCl (10 mol%). The resulting deep purple solution was
stirred at this temperature for 3 h and then diluted with water
(50 mL). The aqueous phase was extracted with EtOAc (50 mL
× 3) and the combined extracts were dried over anhydrous
3
-(4-Fluorophenyl)[1,2,4]triazino[6,5-f ]quinoline 11b. Mp
1
61–163 ЊC; δH (CDCl ) 7.30 (d, 2H, J = 8.8), 7.83 (dd, 1H,
J = 4.4, 8.4), 8.15 (d, 1H, J = 9.2), 8.50 (d, 1H, J = 9.2), 8.82 (d,
H, J = 8.8), 9.18 (dd, 1H, J = 1.6, 4.4), 9.77 (dd, 1H, J = 1.6,
.4); δC (CDCl ) 116.1 (2C), 123.9, 125.2, 129.5, 130.9 (2C),
3
2
8
1
3
31.9, 139.7, 142.6, 143.9, 148.7, 152.9, 161.1, 164.1, 166.6;
ϩ
m/z (CI) 277 (M ϩ 1, 100%), 251 (22), 190 (30); νmax (KBr)/
MgSO . The solvent was removed under reduced pressure and
4
Ϫ1
cm 1599, 1514, 1450, 1391, 1225, 1157, 1053, 853, 768, 596,
the residue was chromatographed on silica gel using a mixture
of EtOAc and hexane (1 : 3 to 1 : 1) as the eluent to obtain the
5
6
50 (Found: C, 69.47; H, 3.32; N, 20.21. C H FN requires C,
9.56; H, 3.28; N, 20.28%).
16 9 4
2
N -(6-nitroquinolin-5-yl) derivative of 9f (0.073 g, 14%).
2
1
2
3
-(4-Chlorophenyl)[1,2,4]triazino[6,5-f ]quinoline 11c. Mp
N -Methyl-N -(4-methylbenzylidene)-N -(6-nitroquinolin-5-
yl)hydrazine 14. Mp 225–227 ЊC; δ (CDCl ) 2.33 (s, 3H), 3.56
2
54–255 ЊC; δH (CDCl ) 7.59 (d, 2H, J = 8.0), 7.83 (dd, 1H,
3
H
3
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702
701

View Online
(
s, 3H), 7.14 (d, 2H, J = 7.9), 7.43 (d, 2H, J = 7.9), 7.55 (dd, 1H,
6-Chloro-3-(4-nitrophenyl)-1H-indazole 16b. Mp 203–204 ЊC;
δ (CDCl ) 7.45 (dd, 1H, J = 1.8, 8.8), 7.52 (d, 1H, J = 8.8), 8.02
(d, 1H, J = 1.8), 8.14 (d, 2H, J = 8.8), 8.39 (d, 2H, J = 8.8), 10.34
J = 4.1, 8.5), 7.61 (s, 1H), 8.00 (d, 1H, J = 8.4), 8.03 (d, 1H,
J = 8.4), 8.53 (dd, 1H, J = 1.2, 8.5), 9.03 (dd, 1H, J = 1.2, 4.1);
H
3
δC (CDCl ) 39.9, 41.3, 123.6, 125.3, 125.5, 127.1 (2C), 128.6
(s, 1H); δC (DMSO-d ) 112.8, 119.6, 120.9, 124.2 (2C), 126.6,
3
6
ϩ
(
1
2C), 130.2, 132.5, 132.8, 134.5, 136.5, 138.1, 138.6, 140.7,
126.9, 127.4 (2C), 139.5, 140.3, 140.8, 146.5; m/z (EI) 274 (M ,
ϩ
Ϫ1
43.3; m/z (EI) 320 (M , 100%), 274 (36), 259 (22); ν (KBr)/
21%), 273 (100), 243 (32), 192 (32), 164 (37); νmax (KBr)/cm
max
Ϫ1
cm 1599, 1532, 1478, 1393, 1356, 1316, 1065, 897, 843, 812,
3245 (NH), 1599, 1518, 1478, 1346, 1316, 1109, 922, 856, 789,
718 (Found: C, 57.14; H, 3.08; N, 15.51. C H ClN O requires
7
77, 519 (Found: C, 67.20; H, 5.06; N, 17.35. C H N O
18 16 4 2
13
8
3
2
requires C, 67.49; H, 5.03; N, 17.49%).
C, 57.05; H, 2.95; N, 15.35%).
1
2
N -(4-Methylbenzylidene)-N -(6-nitroquinolin-5-yl)hydrazine
7. Mp 191–192 ЊC; δH (CDCl ) 2.42 (s, 3H), 7.28 (d, 2H,
6
-Nitro-3-(4-nitrophenyl)-1H-indazole 16c. Mp >300 ЊC;
1
3
δ (DMSO-d ) 7.27 (d, 2H, J = 8.8), 7.99 (d, 2H, J = 8.8), 8.13
s, 1H), 8.18 (d, 1H, J = 9.2), 8.27 (d, 1H, J = 9.2), 11.65 (s, 1H);
δC (DMSO-d ) 112.0 (2C), 124.1, 124.4, 126.1 (2C), 127.1,
127.9, 139.0, 139.3, 141.2, 147.0, 150.0; m/z (EI) 284 (M ,
00%), 254 (26), 192 (40), 164 (42); νmax (KBr)/cm 3374 (NH),
603, 1526, 1470, 1348, 1319, 1111, 1074, 858, 814, 789, 750,
698 (Found: C, 54.77; H, 3.35; N, 19.34. C H N O requires C,
4.93; H, 2.84; N, 19.71%).
H
6
J = 8.4), 7.47 (dd, 1H, J = 4.4, 8.8), 7.49 (d, 1H, J = 9.6), 7.63
d, 2H, J = 8.4), 8.39 (d, 1H, J = 9.6), 8.98 (dd, 1H, J = 1.2, 4.4),
.86 (dd, 1H, J = 1.2, 8.8), 12.64 (s, 1H); δC (CDCl ) 22.21,
20.3, 122.0, 124.1, 125.8, 126.5 (2C), 128.1 (2C), 129.0, 130.6,
38.2, 139.8, 141.2, 146.8, 148.3, 152.3; m/z (CI) 307 (M ϩ 1,
00%), 247 (22), 190 (27); νmax (KBr)/cm 3121 (NH), 1609,
512, 1460, 1408, 1370, 1279, 1233, 1171, 1144, 1098, 804, 772,
69, 511 (Found: C, 66.36; H, 4.65, N, 18.04. C H N O
(
(
9
6
ϩ
3
1
1
1
Ϫ1
1
1
ϩ
Ϫ1
13
8
4
4
1
5
6
17
14
4
2
requires C, 66.66; H, 4.61; N, 18.29%).
Acknowledgements
1
2
N -(2,4-Dinitrophenyl)-N -(4-methylbenzylidene)hydrazine
2a. Mp 203–204 ЊC; δH (CDCl ) 2.39 (s, 3H), 7.12 (d, 1H,
We are thankful to Professor Hidemitsu Uno, Advanced
Instrumentation Center, Ehime University, for elemental
analysis.
2
3
J = 9.2), 7.22 (d, 2H, J = 8.0), 7.59 (d, 2H, J = 8.0), 7.79 (s, 1H),
8
1
1
.02 (br, 1H), 8.15–8.20 (m, 2H); δ (CDCl ) 21.6, 116.8, 123.5,
C 3
27.6 (2C), 129.8 (2C), 130.0, 130.4, 138.1, 141.6, 144.8, 148.0,
ϩ
References
48.1; m/z (EI) 300 (M , 68%), 152 (38), 121 (100); ν (KBr)/
max
Ϫ1
cm 3287 (NH), 1618, 1586, 1507, 1422, 1331, 1136, 1084
1
J. M. Brown, Br. J. Cancer, 1993, 67, 1163.
(
Found: C, 55.96; H, 4.07; N, 18.27. C H N O requires C,
2 D. I. Edwards, J. H. Tocher, L. D. Dale, D. Widdick and N. S. Virk,
Selective Activation Drugs by Redox Process, ed. G. E. Adams,
Plenum, New York, 1990, p. 275.
14
12
4
4
5
6.00; H, 4.03; N, 18.66%).
1
2
3 J. S. Daniels and K. S. Gates, J. Am. Chem. Soc., 1996, 118,
N -(4-Methylbenzylidene)-N -(4-nitrophenyl)hydrazine 22b.
3
380.
Mp 236–238 ЊC; δ (CDCl ) 2.39 (s, 3H), 7.12 (d, 2H, J = 8.8),
H
3
4
F. J. Wolf and K. Pfister, US Pat, 2 489 352, 1949 (Chem. Abstr.,
950, 44, 3536g).
7
1
.22 (d, 2H, J = 8.0), 7.59 (d, 2H, J = 8.0), 7.78 (s, 1H), 7.99 (br,
H), 8.18 (d, 2H, J = 8.8); δ (CDCl ) 13.5, 110.8 (2C), 112.4
1
C
3
5 Y. Sanemitsu, Y. Nakayama, Y. Tanabe and H. Matsumoto, Agric.
Biol. Chem., 1990, 54, 3367.
(
2C), 125.4 (2C), 125.9, 127.0 (2C), 127.5, 128.7, 130.3, 131.4;
ϩ
m/z (EI) 255 (M , 100%), 240 (3), 225 (4), 208 (13); ν (KBr)/
cm 3258 (NH), 1610, 1595, 1495, 1480, 1300, 1275, 1173,
6
G. D. Daves, Jr., R. K. Robins and C. C. Cheng, J. Org. Chem., 1961,
26, 5256.
max
Ϫ1
7
8
H. J. Lindner and G. Schaden, Chem. Ber., 1972, 105, 1949.
For details, see Comprehensive Heterocyclic Chemistry II, ed.
A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press,
New York, 1996, vols. 6 and 7; Comprehensive Heterocyclic
Chemistry I, ed. A. R. Katritzky and C. W. Rees, Pergamon Press,
New York, 1984, vols. 3 and 5.
1
107, 837, 818, 750, 513 (Found: C, 65.82; H, 5.15; N, 16.46.
C H N O requires C, 65.87; H, 5.13; N, 16.46%).
14
13
3
2
Synthesis of 3-aryl-1H-indazoles 16. Typical procedure
A mixture of 1,3-dinitrobenzene 15a (0.29 g, 1.7 mmol) and
NaH (0.29 g, 7.0 mmol) in DMF (15 mL) was cooled to Ϫ10 ЊC
and 4-nitrobenzaldehyde hydrazone 9a (0.33 g, 2.0 mmol) was
added in one portion. The resulting deep purple solution was
stirred at this temperature for 12 h and then diluted with water
9
Y. Morioka, E. Matsumoto, T. Kawakami and H. Suzuki, to be
published.
10 Y. Fukumoto, K. Uehata and H. Suzuki, to be published.
1
1
1
1 T. Kawakami and H. Suzuki, Tetrahedron Lett., 1999, 40, 1157.
2 H. Suzuki and T. Kawakami, J. Org. Chem., 1999, 64, 3361.
3 T. Kawakami and H. Suzuki, J. Chem. Soc., Perkin Trans. 1, 2000,
(
(
50 mL). The aqueous mixture was extracted with EtOAc
50 mL × 3) and the combined extracts were dried over
1
259.
1
4 T. Kawakami and H. Suzuki, J. Chem. Soc., Perkin Trans. 1, 2000,
anhydrous MgSO and evaporated under reduced pressure. The
3640.
4
residue was chromatographed on silica gel using a mixture of
EtOAc and hexane (1 : 5 to 1 : 1) as the solvent to give 3-aryl-
15 S. Seko, K. Miyake and N. Kawamura, J. Chem. Soc., Perkin
Trans. 1, 1999, 1437.
1
6 M. Wozniak, A. Baranski, K. Nowak and H. C. van der Pals, J. Org.
Chem., 1987, 52, 5643.
1
H-indazole 16a as a light brown powder (0.18 g, 37%).
1
7 M. Makosza and K. Sienkiewicz, J. Org. Chem., 1998, 63,
5
-Nitro-3-(4-nitrophenyl)-1H-indazole 16a. Mp 210–212 ЊC;
4
199.
δ (DMSO-d ) 7.71 (m, 3H), 8.07 (d, 1H, J = 8.0), 8.14 (d, 1H,
18 A. Halama, J. Kavalek, V. Machacek and T. Weidlich., J. Chem.
Soc., Perkin Trans. 1, 1999, 1839.
H
6
J = 8.0), 8.31 (d, 2H, J = 8.5), 14.38 (s, 1H); δC (DMSO-d6)
1
2
2
9 E. Tomitori, T. Okamoto and T. Ido, Yakugaku Zasshi, 1983, 103,
1
1
17.8, 119.1, 122.9 (3C), 126.2, 130.0 (2C), 140.8, 141.7, 141.8,
ϩ
601.
43.2, 146.8; m/z (EI) 284 (M , 100%), 254 (18), 208 (50), 179
0 N. R. Ayyangar, S. N. Naik and K. V. Srinivasan, Tetrahedron Lett.,
Ϫ1
(
44), 152 (43); νmax (KBr)/cm 3349 (NH), 1599, 1516, 1346,
1
990, 31, 3217.
1
326, 1105, 988, 858, 795, 733, 704 (Found: C, 54.88; H, 2.94;
1 M. K. Stern, F. D. Hileman and J. K. Bashkin, J. Am. Chem. Soc.,
1992, 114, 9237.
N, 19.44. C H N O requires C, 54.93; H, 2.80; N, 19.71%).
13
8
4
4
7
02
J. Chem. Soc., Perkin Trans. 1, 2002, 696–702