Synthesis of 3-substituted 1-aryl-4,6-dinitro-1H-indazoles based on picrylacetaldehyde and their behavior in nucleophilic substitution reactions

Article abstract of DOI:10.1023/A:1026008821698

A method for the synthesis of 1-aryl-3-formyl-4,6-dinitro-1H-indazoles by the reaction of picrylacetaldehyde with aryldiazonium salts followed by intramolecular cyclization of the resulting picrylglyoxal monoarylhydrazones was developed. Various 4,6-dinitro-1-phenyl-1H-indazoles substituted in position 3 were prepared via transformations involving the formyl group of 3-formyl-4,6-dinitro-1-phenyl-1H-indazole. 3-R-4,6-Dinitro-1-phenyl-1H- indazoles (R = CHO, CN, 1,3-dioxolan-2-yl) react regiospecifically with anionic O-, S-, and N-nucleophiles, in particular, with replacement of only the 4-NO₂ group. Thus previously unknown 3-R-4-Nu-6-nitro-1-phenyl-1H- indazoles were synthesized (Nu is a nucleophile residue).

Full text of DOI:10.1023/A:1026008821698

1782
Russian Chemical Bulletin, International Edition, Vol. 52, No. 8, pp. 1782—1790, August, 2003
Synthesis of 3ꢀsubstituted
1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles based on picrylacetaldehyde and
their behavior in nucleophilic substitution reactions
ꢀ
A. M. Starosotnikov, V. V. Kachala, A. V. Lobach, V. M. Vinogradov, and S. A. Shevelev
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: shevelev@mail.ioc.ac.ru
A method for the synthesis of 1ꢀarylꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles by the reaction of
picrylacetaldehyde with aryldiazonium salts followed by intramolecular cyclization of the
resulting picrylglyoxal monoarylhydrazones was developed. Various 4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀ
indazoles substituted in position 3 were prepared via transformations involving the formyl
group of 3ꢀformylꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole. 3ꢀRꢀ4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazoles
(R = CHO, CN, 1,3ꢀdioxolanꢀ2ꢀyl) react regiospecifically with anionic Oꢀ, Sꢀ, and Nꢀnucleoꢀ
philes, in particular, with replacement of only the 4ꢀNO2 group. Thus previously unknown
3ꢀRꢀ4ꢀNuꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazoles were synthesized (Nu is a nucleophile residue).
Key words: picrylacetaldehyde, 1Hꢀindazoles, formyl group, nitro group, nucleophilic
substitution, condensations, cyclizations.
Previously,1 we reported on the development of a
To prepare 1ꢀarylꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles,
PAA was first introduced in the reactions with arylꢀ
diazonium salts in a weakly acid medium; this gave
azo coupling products, namely, monoarylhydrazones of
picrylglyoxal 3a—c (Scheme 1).
method for the preparation of picrylacetaldehyde (PAA)
from 2,4,6ꢀtrinitrotoluene. Within the framework of our
research dealing with PAA as a multipurpose synthon, we
found that this compound can serve as a precursor for the
synthesis of diverse heterocyclic products with a new comꢀ
bination of functional substituents. In particular, we deꢀ
veloped PAAꢀbased syntheses of 6ꢀnitrobenzo[d]isoxazoꢀ
les 1 2 and 2,4ꢀdisubstituted 1,2,3ꢀtriazoles of type 2.3
Scheme 1
Pic = 2,4,6ꢀ(NO2)3C6H2
Compound
Ar
Yield (%)
3a
3b
3c
Ph
79
66
71
4ꢀClꢀC6H4
4ꢀMeOꢀC6H4
It should be noted that the рH of the diazonium salt
solution plays an important role in these reactions. The
maximum product yields were attained at рH 5 when
AcONa was used to neutralize excess acid. Compounds
3a—c are relatively unstable and decompose during puriꢀ
fication. Therefore, they were not fully characterized and
were used in the subsequent reactions without additional
purification.
Here we developed a convenient method for the prepaꢀ
ration of 1ꢀarylꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles from
PAA (for preliminary communication, see Ref. 4) and
used these products to obtain various 3,4ꢀdisubstituted
1ꢀarylꢀ6ꢀnitroꢀ1Hꢀindazoles.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1690—1697, August, 2003.
1066ꢀ5285/03/5208ꢀ1782 $25.00 © 2003 Plenum Publishing Corporation

Synthesis of 1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1783
Previously unknown 1ꢀarylꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀ
indazoles (4a—c) (Scheme 2) were formed upon treatꢀ
ment of hydrazones 3a—c with alkalis or alkali metal
carbonates; the best results were attained with K2CO3 in
EtOH at room temperature. Cyclization of hydrazones
3a—c is due to intramolecular nucleophilic replacement
of the nitro group (see Scheme 2).
up to complete conversion of the starting indazole 4a and
was carried out at ∼20 °C in the case of NaN3 and
benzenethiol or at 80 °C in the case of phenol. In the case
of alkanethiols, the reaction does proceed at 20 °C but
conducting it at 60 °C is more convenient. It should be
noted that the outcome does not depend on whether alꢀ
dehyde 4a or its hemiacetal 5a is used as the starting
compound.
Scheme 2
Scheme 3
i. K2CO3, EtOH, 20 °C, 24 h.
Compound
Ar
Yield (%)
Reagents and conditions: i. NaN3, DMF, 20 °C; ii. PhOH,
K2CO3, NMP, 80 °C; iii. RSH, K2CO3, NMP, 20—60 °C.
4a
4b
4c
Ph
91
86
82
4ꢀClꢀC6H4
4ꢀMeOꢀC6H4
Compound
R
Yield (%)
8a
8b
8c
Ph
CH2Ph
cycloꢀC6H11
95
90
89
Dinitroformylindazoles 4 can also be obtained in satisfacꢀ
tory overall yields without isolation of intermediate
hydrazones 3.
A characteristic feature of formyldinitroindazoles 4,
containing no electronꢀdonating groups in the Nꢀaryl subꢀ
stituent, is transformation into stable hemiacetals 5a,b,
which occurs to some extent even during the synthesis of
compounds 4 (see Scheme 2). Complete transformation
into hemiacetals 5a,b takes place on refluxing in EtOH
for 30 min. On heating in air (80 °C, 8 h), crystalline
hemiacetal 5a splits off an ethanol molecule to recover
formyldinitroindazole 4a.
The formation of only one of the two possible prodꢀ
ucts of replacement of the nitro group was proved by
1H NMR spectroscopy of the crude reaction product,
both for this reaction and for other 3ꢀsubstituted dinitroꢀ
indazoles. The fact that the 4ꢀNO2 group is replaced was
confirmed in the following way. For the starting 3ꢀformylꢀ
4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole (4a), all the carbon and
1
hydrogen signals observed in the H and 13C NMR specꢀ
1
tra were assigned using 1D NOE and 2D H—13C techꢀ
3ꢀFormylꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole (4a) was
taken as an example to study the transformations of
formyldinitroindazoles. This compound was found to have
an interesting feature, namely, it reacts with anionic Nꢀ,
Oꢀ, and Sꢀnucleophiles (in DMF or Nꢀmethylpyrrolidone
(NMP)) to replace only the nitro group in position 4
giving rise to previously unknown 4ꢀsubstituted 3ꢀformylꢀ
6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazoles 6—8 as the only products
(Scheme 3). The nucleophiles used were phenol and thiꢀ
ols in the presence of solid K2CO3 (equimolar amount) as
a deprotonating agent and NaN3. The reaction proceeded
niques (HSQC, HMBC). In the case of formylmonoꢀ
nitroindazoles 6—8, formed upon replacement of the nitro
group, the signal of the C(4) atom substantially shifts
upfield compared to that in the spectrum of the initial
formyldinitroindazole 4a, while the chemical shift of C(6)
remains virtually the same. An additional and indepenꢀ
dent piece of evidence for the replacement of the 4ꢀNO2
group is the fact that the NOESY spectrum of formylꢀ
mononitroindazole 8a reflects throughꢀspace interacꢀ
tion between the formyl group proton and the phenyl
orthoꢀprotons in the SPh substituent. The pattern of reꢀ

1784
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Starosotnikov et al.
Scheme 5
placement of the nitro group was also demonstrated by a
chemical procedure. The reaction of 4a with thioglycerol
gave glycol 9, which was converted into intramolecular
cyclic acetal 10 in the presence of paraꢀtoluenesulfonic
acid as a catalyst (Scheme 4). This product could form
only in the case of replacement of the nitro group located
in the periꢀposition to the formyl group, i.e., in position 4.
Scheme 4
The reaction of aldehyde 4a with hydroxylamine
hydrochloride in AcOH gave oxime 13 (Scheme 6), which
splits off a water molecule on treatment with Ac2O to give
previously unknown 3ꢀcyanoꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀ
indazole (14).
Scheme 6
Reagents and conditions: i. HSCH2CH(OH)CH2OH, K2CO3,
NMP, 20 °C; ii. TsOH, C6H6, 80 °C.
In order to prepare new 3ꢀsubstituted 4,6ꢀdinitroꢀ1Hꢀ
indazoles, we studied transformations of formyldinitroꢀ
indazole 4a involving the formyl group. On treatment
with ethylene glycol in chloroform in the presence of
catalytic amounts of TsOH, dinitroindazole 4a is conꢀ
verted into cyclic acetal 11 in a good yield (Scheme 5).
The reaction with phenylmethanethiol was used to
demonstrate that the nitro group in dioxolane derivaꢀ
tive 11 can also be substituted on treatment with a nuꢀ
cleophile but under more drastic conditions than that
in 3ꢀformylꢀ4,6ꢀdinitroindazoles. The reaction with
PhCH2SH proceeds only at 80 °C (in NMP in the presꢀ
ence of К2CO3, see Scheme 5), whereas in the case of 4a,
it can be carried out at ∼20 °C. It should be noted that the
process is regiospecific, i.e., only the nitro group in posiꢀ
tion 4 is replaced. This is indicated by the substantial
change in the chemical shift of the C(4) atom in prodꢀ
uct 12 compared to that in the starting dinitro deꢀ
rivative 11, for which full assignment of the hydroꢀ
gen and carbon signals was performed using NOE and
1H—13C 2D NMR techniques. The chemical shifts of the
other carbon atoms in compound 12 remained virtually
the same.
Reagents and conditions: i. NH2OH•HCl, AcOH; ii. Ac2O,
140 °C.
We found that in the case of nitrile 14, too, the nitro
group in position 4 is highly reactive. In particular, only
the 4ꢀNO2 group is replaced on treatment with anionic
Nꢀ, Oꢀ, and Sꢀnucleophiles (in NMP or DMF). This
gives 4ꢀsubstituted 3ꢀcyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindꢀ
azoles 15—17 usually in high yields and under mild conꢀ
ditions (Scheme 7). The nucleophiles used included pheꢀ
nol, 2,2,3,3ꢀtetrafluoropropanꢀ1ꢀol, and thiols in the presꢀ

Synthesis of 1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1785
ence of К2CO3, and NaN3 (see Scheme 7). In the case of
NaN3 and thiols, the reaction proceeds at ∼20 °C and in
the case of Oꢀnucleophiles, at 80 °C.
spectroscopy, as in the case of formyldinitroindazole 4a
(see above). Due to the low solubility of nitrile 14, we
were unable to record a satisfactory 13C NMR spectrum
for this compound. In the case of derivative 17c, throughꢀ
space interaction between the protons of the methylene
fragment and H(5) was detected by 1H NMR spectroꢀ
scopy using the NOE procedure. In addition, interaction
between H(7) and the phenyl orthoꢀprotons was found in
molecule 17c. These facts provide the conclusion that the
group replaced is the nitro group in position 4. We asꢀ
signed all the carbon signals from derivative 17c using a
number of NMR techniques (NOE, HMBC) and found
the chemical shifts for the C(4) (132.2 ppm) and C(6)
(147.7 ppm) atoms. The 13C NMR spectra of any of
cyanomononitroindazoles 15—17, formed upon replaceꢀ
ment of the nitro group, exhibit signals in the region of
δ 147—149 for C(6) and in the region of δ 132—135 for
C(4). These results allowed us to conclude unambiguꢀ
ously that only the nitro group in position 4 was substiꢀ
tuted under the action of any nucleophile. The rates of
replacement of the nitro group in nitrile 14 and in
3ꢀformylindazole 4a do not probably differ much, as comꢀ
plete conversion of these compounds on treatment with
the same nucleophile (NaN3, PhSH/K2CO3) under idenꢀ
tical conditions requires nearly equal time periods.
Thus, we developed a general method for the synthesis
of 3ꢀcyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazoles with various
substituents in position 4.
Scheme 7
Reagents and conditions: i. NaN3, DMF, 20 °C; ii. ROH, K2CO3,
NMP, 80 °C; iii. RSH, K2CO3, NMP, 20 °C.
Compound
R
Yield (%)
16a
16b
17a
17b
17c
Ph
CH2CF2CHF2
Ph
CH2Ph
CH2CO2Me
87
18
98
98
98
The formation of stable hemiacetals 5a,b from formylꢀ
dinitroindazoles 4a,b (see Scheme 2) attests to high elecꢀ
trophilicity of the formyl group in these molecules. This
feature of formyldinitroindazoles 4 was used to study the
reactions of dinitro derivative 4a with compounds conꢀ
The regiospecificity of the nucleophilic substitution (reꢀ
placement of only the 4ꢀNO2 group) was proved by NMR
Scheme 8
Reagents and conditions: i. CH2(CN)CO2Et (1 equiv.), NH4OAc (10 mol. %), AcOH (10 mol. %), benzene, 80 °C, 6 h; ii. CH2(CO2H)2,
NH4OAc (2 equiv.), EtOH, 78 °C, 5 h; iii. CH2(CO2H)2, NH4OAc (3 equiv.), AcOH, 118 °C, 10 h; iv. CH2(CO2H)2, piperidine
(10 mol. %), Py, 115 °C, 5 h.

1786
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Starosotnikov et al.
taining an activated methylene fragment. Reactions of
this type proceed very easily, for example, the reaction
with ethyl cyanoacetate yields unsaturated compound 18
(Scheme 8). Of special note are the results of reaction of
formyldinitroindazole 4a with malonic acid. Different
products can be formed depending on the conditions.
The reaction carried out in EtOH in the presence of
NH4OAc gave a methylenemalonic acid derivative 19,
while heating in pyridine in the presence of piperidine as
the catalyst gave an acrylic acid derivative 20, i.e., under
these conditions, dicarboxylic acid 19 is decarboxylated.
If the reaction is carried out in the presence of excess
NH4OAc but in acetic acid (Rodionov reaction condiꢀ
tions5), two products are formed in roughly the same
amounts, namely, acrylic acid derivative 20 (yield 28%)
and 3ꢀaminopropionic acid derivative 21 (yield 20%). It
was found that acid 20 does not add ammonia under the
reaction conditions and amino acid 21 is not formed.
Meanwhile, methylenemalonic acid 19 is converted unꢀ
der these conditions to give a mixture of acids 20 and 21
in 20 and 32% yields, respectively. Thus, one can conꢀ
clude that the reaction of formyldinitroindazole 4a with
malonic acid in the presence of NH4OAc in acetic
acid gives first dicarboxylic acid 19. Under the reaction
conditions, this product is either decarboxylated to give 20
or adds ammonia and is subsequently decarboxylated to
give amino acid 21, the rates of these reactions being
similar.
In this respect, 4a resembles aliphatic aldehydes (CH2O,
Х3CCHO, Х = F, Cl), which also react with TNT to give
alcohols, rather than aromatic aldehydes.7 This fact conꢀ
firms once again the high reactivity of the carbonyl group
in 3ꢀformylindazoles 4.
3ꢀFormylindazoles 4a and 8c react with ethyl acetoꢀ
acetate under the Hantzsch reaction conditions8 (refluxing
in an alcohol solution of ammonia) to give 1,4ꢀdihydroꢀ
pyridine derivatives 23a,b (Scheme 10).
Scheme 10
23a: R = NO2, yield 13%
23b: R = Sꢀ(cyclo)ꢀC6H11, yield 70%
Formyldinitroindazole 4a reacts with 2,4,6ꢀtrinitroꢀ
toluene (TNT) in an unusual way. Heating aromatic and
heteroaromatic aldehydes with TNT in the presence of
bases is known to give the corresponding stilbenes or their
heteroaromatic analogs (see Ref. 6 and references cited
therein). Indazole 4a reacts with TNT even at room temꢀ
perature (in the presence of К2CO3 in EtOH) to give
alcohol 22 in a high yield (Scheme 9). No dehydration
product of alcohol 22 was detected.
However, the reaction of mononitroꢀsubstituted forꢀ
mylindazole 8c with acetylacetone under the same condiꢀ
tions follows a different route, giving rise to unsaturated
compound 24 (Scheme 11).
Scheme 11
Scheme 9

Synthesis of 1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1787
400 mL of water. The precipitate was filtered off, dried in air,
and used without further purification.
Formyldinitroindazole 4a is smoothly oxidized by 30%
hydrogen peroxide in acetic acid to give the correspondꢀ
ing acid, namely, 4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazoleꢀ3ꢀ
carboxylic acid (25) (Scheme 12).
2ꢀ(2ꢀPhenylhydrazono)ꢀ2ꢀ(2,4,6ꢀtrinitrophenyl)acetaldehyde
1
(3a). H NMR: 7.05 (m, 1 H, Ph); 7.30 (m, 4 H, Ph); 9.21 (s,
2 H, Pic); 9.53 (s, 1 H, CHO); 11.11 (s, 1 H, NH).
2ꢀ[2ꢀ(4ꢀChlorophenyl)hydrazono]ꢀ2ꢀ(2,4,6ꢀtrinitropheꢀ
nyl)acetaldehyde (3b). 1H NMR: 7.32 (m, 4 H, pꢀClC6H4); 9.21
(s, 2 H, Pic); 9.56 (s, 1 H, CHO); 11.12 (s, 1 H, NH).
2ꢀ[2ꢀ(4ꢀMethoxyphenyl)hydrazono]ꢀ2ꢀ(2,4,6ꢀtrinitropheꢀ
Scheme 12
1
nyl)acetaldehyde (3c). H NMR: 3.79 (s, 3 H, CH3); 6.90, 7.25
(both d, each 2 H, pꢀMeOC6H4); 9.20 (s, 2 H, Pic); 9.47 (s, 1 H,
CHO); 11.10 (s, 1 H, NH).
Preparation of 1ꢀarylꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles
(4a—c) (general procedure). Potassium carbonate (2.76 g,
20 mmol) was added to a solution of picrylglyoxal monoarylꢀ
hydrazone (20 mmol) in 220 mL of EtOH. The mixture was
stirred for 24 h and the precipitate was filtered off, washed with
water, recrystallized from EtOH, and dried at 80 °C (drying in
air at 20 °C results in hemiacetals 5a and 5b).
3ꢀFormylꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole (4a). M.p.
190 °C (EtOH). Found (%): C, 53.44; H, 2.76. C14H8N4O5.
Calculated (%): C, 53.85; H, 2.58. 1H NMR: 7.60—7.80 (m,
3 H, Ph); 7.90 (m, 2 H, Ph); 8.75 (s, 1 H, H(5)); 8.85 (s, 1 H,
H(7)); 10.35 (s, 1 H, CHO). 13C NMR: 113.2 (C(7)), 114.8
(C(5)), 115.9 (C(3a)), 124.5 (оꢀPh), 129.9 (pꢀPh), 130.2 (mꢀPh),
137.2 (ipsoꢀPh), 140.7 (C(7a)), 141.7 (C(4)), 142.0 (C(3)), 146.0
(C(6)), 185.4 (CHO).
The structures of the obtained compounds were proved
by 1H and 13C NMR spectroscopy, mass spectrometry
(a molecular ion was recorded in all cases), and IR specꢀ
troscopy (νas(NO2) at 1540—1560 cm–1, νs(NO2) at
1340—1360 cm–1, ν(CN) at 2220—2240 cm–1, and
ν(CHO) 1695—1715 cm–1) and confirmed by elemental
analysis.
Thus, as a result of this research, we developed conveꢀ
nient methods for the synthesis of previously unknown
3ꢀsubstituted 1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles, which
were used to prepare a number of new 3ꢀRꢀ4ꢀR´ꢀ6ꢀnitroꢀ
1ꢀphenylꢀ1Hꢀindazoles.
1ꢀ(4ꢀChlorophenyl)ꢀ3ꢀformylꢀ4,6ꢀdinitroꢀ1Hꢀindazole (4b).
M.p. 218—220 °C (EtOH). Found (%): C, 48.21; H, 2.43.
C
14H7ClN4O5. Calculated (%): C, 48.50; H, 2.04. 1H: 7.70,
7.90 (both d, each 2 H, 4J = 8.8); 8.60 (s, 1 H, H(5)); 8.80 (s,
1 H, H(7)); 10.40 (s, 1 H, CHO).
Experimental
3ꢀFormylꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ4,6ꢀdinitroꢀ1Hꢀindazole
(4c). M.p. 210—212 °C (EtOH). Found (%): C, 52.81; H, 3.23.
1
15H10N4O6. Calculated (%): C, 52.64; H, 2.94. 1H NMR: 3.92
H NMR spectra were recorded on a Bruker ACꢀ200 specꢀ
C
trometer and 13C NMR spectra were run on a Bruker AMꢀ300
instrument. The chemical shifts (δ) are referred to tetramethylꢀ
silane. The spinꢀspin coupling constants are given in Hz. All the
samples for NMR spectroscopy were prepared in a 1 : 1
DMSOꢀd6—CCl4 mixture. IR spectra were measured on a
Specord Mꢀ80 instrument for KBr pellets. Mass spectra were
run on a MSꢀ30 Kratos mass spectrometer (always EI, 70 eV).
The mass spectrum of compound 22 was obtained on a Finnigan
LCQ instrument (electrospray ionization in the negative ion
mode). The reactions were monitored and the purity of comꢀ
pounds was checked by TLC on Silufol UVꢀ254 plates. The
solvents were not specially dried.
(s, 3 H, OCH3); 7.22, 7.75 (both d, each 2 H, 3J = 8.85 Hz);
8.76 (s, 2 H, H(5) and H(7)); 10.32 (s, 1 H, CHO).
Hemiacetals 5a,b were not obtained in an analytically pure
state. Their melting points were not determined either, as during
heating, they lose an EtOH molecule before melting.
(4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀyl)(ethoxy)methanol
(5a). 1H NMR: 1.14 (t, 3 H, Me, 3J = 6.96 Hz); 3.54, 3.87
(both m, each 1 H, CH2); 5.95, 6.69 (both d, each 1 H, OCH
3
and OH, JH,H = 9.11 Hz); 7.50—7.90 (m, 5 H, Ph); 8.53, 8.77
4
(both d, each 1 H, H(5) and H(7), J = 1.60 Hz).
[1ꢀ(4ꢀChlorophenyl)ꢀ4, 6ꢀdinitroꢀ1Hꢀindazolꢀ3ꢀ
yl](ethoxy)methanol (5b). 1H NMR: 1.13 (t, 3 H, Me, 3J =
6.99 Hz); 3.50, 3.82 (both m, each 1 H, CH2); 5.89, 6.83 (both d,
each 1 H, OCH and OH, 3J = 9.32 Hz); 7.68, 7.89 (both d,
each 2 H, pꢀClC6H4, 3J = 8.85 Hz); 8.53, 8.80 (both s, each 1 H,
H(5) and H(7)).
Preparation of 4ꢀazidoꢀ6ꢀnitroꢀ1ꢀphenylindazoles 6 and 15
(general procedure). A mixture of compound 4a or 14 (1 mmol),
NaN3 (0.07 g, 1 mmol), and 5 mL of DMF was stirred for 24 h at
20 °C. The reaction mixture was poured in water and acidified
to рH 2. The precipitate was filtered off and recrystallized
from EtOH.
Preparation of picrylglyoxal monoarylhydrazones 3a—c (genꢀ
eral procedure). A solution of NaNO2 (0.7 g, 10 mmol) was
added dropwise at 0—5 °C to a solution of ArNH2•HCl
(10 mmol) in a mixture of 3 mL of concentrated HCl and 3 mL
of water. The mixture was stirred for 5 min and AcONa (2.8 g)
was added portionwise at 0—5 °C (solution рH ∼5). A suspenꢀ
sion of finely ground* picrylacetaldehyde (2 g, 7.8 mmol) in
40 mL of EtOH was added to the resulting solution. The reacꢀ
tion mixture was stirred for 1 h at 0—5 °C and poured into
* Caution! Picrylacetaldehyde is a potentially explosive subꢀ
stance. Grinding should be carried out with caution. For exꢀ
ample, this can be done in an agate mortar with an agate pestle.
4ꢀAzidoꢀ3ꢀformylꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazole (6). M.p.
194—195 °C (EtOH). Found (%): C, 54.81; H, 2.38. C14H8N6O3.
Calculated (%): C, 54.55; H, 2.62. 1H NMR: 7.60—7.90 (m,

1788
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Starosotnikov et al.
5 H, Ph); 8.02 (s, 1 H, H(5)); 8.35 (s, 1 H, H(7)); 10.50 (s,
1 H, CHO).
4ꢀBenzylthioꢀ3ꢀformylꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazole (8b).
M.p. 152—153 °C (EtOH). H NMR: 4.52 (s, 2 H, CH2); 7.29
1
4ꢀAzidoꢀ3ꢀcyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazole (15). M.p.
170—172 °C (EtOH). Found (%): C, 55.01; H, 2.49. C14H7N7O2.
Calculated (%): C, 55.09; H, 2.31. 1H NMR: 7.50—7.90 (m,
5 H, Ph); 8.05 (s, 1 H, H(5)); 8.35 (s, 1 H, H(7)). 13C NMR:
105.1, 107.9, 112.7, 118.7, 120.6, 124.3, 130.1, 130.7, 135.3,
137.9, 139.5, 148.9.
Preparation of 6ꢀnitroꢀ1ꢀphenylꢀ4ꢀphenyloxyꢀ1Hꢀindazoles 7
and 16a (general procedure). A mixture of compound 4a or 14
(1 mmol), phenol (0.094 g, 1 mmol), К2CO3 (0.14 g, 1 mmol),
and NMP (5 mL) was stirred for 8 h at 80 °C. After completion
of the reaction, the mixture was poured in water and acidified
to рH 2. The precipitate was filtered off and recrystallized
from EtOH.
(m, 2 H, Ph); 7.50—7.80 (m, 8 H, Ph); 8.03 (s, 1 H, H(5)); 8.25
(s, 1 H, H(7)); 10.42 (s, 1 H, CHO).
4ꢀCyclohexylthioꢀ3ꢀformylꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazole
(8c). M.p. 173—175 °C (EtOH). 1H NMR: 1.30—1.90,
2.00—2.20 (both m, 10 H, (CH2)5); 3.61 (m, 1 H, SCH);
7.50—7.90 (m, 5 H, Ph); 8.01, 8.30 (both d, each 1 H, H(5) and
H(7), 4J = 1.40 Hz); 10.58 (s, 1 H, CHO).
4ꢀ(2,3ꢀDihydroxypropylthio)ꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazoleꢀ
3ꢀcarboxaldehyde (9). A mixture of compound 4a (0.312 g,
1 mmol), 1ꢀthioglycerol (0.09 mL, 1.1 mmol), К2CO3 (0.14 g,
1 mmol), and NMP (4 mL) was stirred for 24 h at 20 °C. The
reaction mixture was poured in water and acidified to рH 2. The
resulting oil was separated and dried to give 0.24 g of comꢀ
pound 9, which was used without further purification. 1H NMR:
3.10, 3.40 (both m, each 2 H); 3.80 (m, 1 H, CH); 4.50, 5.00
(both br.s, each 1 H, OH); 7.50—7.90 (m, 5 H, Ph); 8.07 (s,
1 H, H(5)); 8.21 (s, 1 H, H(7)); 10.51 (s, 1 H, CHO).
10ꢀNitroꢀ13ꢀphenylꢀ3,16ꢀdioxaꢀ7ꢀthiaꢀ13,14ꢀdiazatetraꢀ
cyclo[6.6.1.12,5.012,15]hexadecaꢀ1(14),8(15),9,11ꢀtetraene (10).
A mixture of compound 9 (0.23 g, 0.63 mmol) and TsOH (50 mg)
in 20 mL of toluene was refluxed for 6 h. The solvent was
evaporated and the residue was washed with water, dried in air,
and recrystallized from an EtOH—benzene mixture (1 : 3) to
give 0.1 g of compound 10. M.p. 175—177 °C (EtOH—benzene,
1 : 3). 1H NMR: 3.20 (s, 2 H, CH2); 4.05 (m, 1 H); 4.52 (d, 1 H,
J = 8.6 Hz); 4.81 (m, 1 H); 6.32 (s, 1 H); 7.50—7.80 (m, 5 H,
Ph); 8.13 (s, 1 H, H(5)); 8.39 (s, 1 H, H(7)).
3ꢀ(1,3ꢀDioxolanꢀ2ꢀyl)ꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole
(11). A mixture of 4a (1.2 g, 3.85 mmol), ethylene glycol
(0.43 mL, 7.7 mmol), TsOH (50 mg), and 30 mL of chloroform
was refluxed for 6 h with a water trap. The reaction mixture was
cooled, the solvent was evaporated, and the residue was chroꢀ
matographed on a column (SiO2, elution with CHCl3) to give
1.15 g of compound 11. M.p. 192—194 °C. Found (%): C, 53.43;
H, 3.14. C16H12N4O6. Calculated (%): C, 53.94; H, 3.39.
1H NMR: 4.02 (s, 4 H, OCH2CH2O); 6.48 (s, 1 H, OCHO);
7.57 (t, 1 H, Ph, J = 7.5 Hz); 7.68 (m, 2 H, Ph); 7.80 (d, 2 H,
Ph, J = 7.5 Hz); 8.63 (s, 1 H, H(5)); 8.78 (s, 1 H, H(7)).
13C NMR: 64.3 (OCH2CH2O), 98.1 (OCHO), 112.1 (C(7)),
112.9 (C(5)), 115.9 (C(3a)), 123.7 (oꢀPh), 128.6 (pꢀPh), 129.7
(mꢀPh), 137.4 (ipsoꢀPh), 140.1 (C(7a)), 141.9 (C(4)), 142.3
(C(3)), 145.3 (C(6)).
3ꢀFormylꢀ6ꢀnitroꢀ1ꢀphenylꢀ4ꢀphenyloxyꢀ1Hꢀindazole (7).
M.p. 192—194 °C (EtOH). Found (%): C, 66.70; H, 3.72.
C
20H13N3O4. Calculated (%): C, 66.85; H, 3.65. 1H NMR:
7.20—7.40 (m, 4 H, Ph); 7.50—7.80 (m, 5 H, H(5), Ph); 7.91
(m, 2 H, Ph); 8.32 (s, 1 H, H(7)); 10.53 (s, 1 H, CHO).
3ꢀCyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ4ꢀphenyloxyꢀ1Hꢀindazole (16a).
M.p. 196—199 °C (EtOH). Found (%): C, 67.71; H, 3.14.
C20H12N4O3. Calculated (%): C, 67.41; H, 3.39. 1H NMR:
7.20—7.50 (m, 4 H, Ph); 7.50—7.90 (m, 7 H, H(5), Ph); 8.33 (s,
1 H, H(7)). 13C NMR: 103.0, 103.5, 113.3, 119.0, 120.9,
121.3, 124.6, 127.0, 130.3, 131.0, 131.5, 138.3, 140.3, 149.5,
152.0, 154.6.
Preparation of compounds 8a and 17a—c (general proceꢀ
dure). A mixture of compound 4a or 14 (1 mmol), the correꢀ
sponding thiol (1 mmol), К2CO3 (0.14 g, 1 mmol), and NMP
(5 mL) was stirred for 24 h at 20 °C. After completion of the
reaction, the mixture was poured in water and acidified to рH 2.
The precipitate was filtered off and recrystallized from EtOH.
3ꢀFormylꢀ6ꢀnitroꢀ1ꢀphenylꢀ4ꢀphenylthioꢀ1Hꢀindazole (8a).
M.p. 199—200 °C (EtOH). Found (%): C, 63.71; H, 3.74;
S, 8.40. C20H13N3O3S. Calculated (%): C, 63.99; H, 3.49;
S, 8.54. 1H NMR: 7.59 (s, 1 H, H(5)); 7.50—7.90 (m, 10 H,
2 Ph); 8.25 (s, 1 H, H(7)); 10.42 (s, 1 H, CHO). 13C NMR:
103.9, 114.7, 120.2, 122.2, 123.8, 129.1, 129.6, 129.8, 130.2,
134.5, 136.5, 137.5, 139.8, 144.3, 147.1, 184.1.
3ꢀCyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ4ꢀphenylthioꢀ1Hꢀindazole (17a).
M.p. 196—198 °C (EtOH). 1H NMR: 7.50—7.80 (m, 11 H,
H(5), Ph); 8.42 (s, 1 H, H(7)).
4ꢀBenzylthioꢀ3ꢀcyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazole (17b).
M.p. 165—168 °C (EtOH). 1H NMR: 4.59 (s, 2 H, CH2);
7.20—7.40 (m, 3 H, Ph); 7.50 (m, 2 H, Ph); 7.60—7.80 (m, 5 H,
Ph); 8.07 (s, 1 H, H(5)); 8.35 (s, 1 H, H(7)).
4ꢀBenzylthioꢀ3ꢀ(1,3ꢀdioxolanꢀ2ꢀyl)ꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀ
indazole (12). Potassium carbonate (0.125 g, 0.9 mmol) was
added to a solution containing compound 11 (0.31 g, 0.87 mmol)
and BnSH (0.1 mL, 0.9 mmol) in NMP (5 mL), and the mixture
was stirred for 8 h at 80 °C. The reaction mixture was poured in
water and acidified to рH 3. The precipitate was filtered
off, washed with water, and recrystallized from EtOH to give
0.23 g of compound 12. M.p. 145—147 °C (EtOH). 1H NMR:
4.00—4.30 (m, 4 H, OCH2CH2O); 4.47 (s, 2 H, CH2); 6.62 (s,
1 H, OCHO); 7.20—7.80 (m, 10 H, Ph); 7.91 (s, 1 H, H(5));
8.22 (s, 1 H, H(7)).
Methyl
2ꢀ[(3ꢀcyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ4ꢀ
1
yl)thio]acetic acid (17c). M.p. 132—135 °C (EtOH). H NMR:
3.75 (s, 3 H, CH3); 4.34 (s, 2 H, CH2); 7.60—7.90 (m, 5 H, Ph);
8.10 (s, 1 H, H(5)); 8.38 (s, 1 H, H(7)). 13C NMR: 33.7 (CH2S),
52.4 (OCH3), 105.6 (C(7)), 112.9 (CN), 115.4 (C(5)), 118.7
(C(3)), 123.8 (оꢀPh), 125.4 (C(3a)), 129.4 (pꢀPh), 129.9 (mꢀPh),
132.2 (C(4)), 137.2 (ipsoꢀPh), 137.8 (C(7a)), 147.7 (C(6)),
168.4 (C=O).
Preparation of compounds 8b,c (general procedure). A mixꢀ
ture of compound 4a (2.6 g, 8.3 mmol), the corresponding thiol
(8.3 mmol), К2CO3 (1.15 g, 8.3 mmol), and NMP (30 mL) was
stirred for 24 h at 60 °C. After completion of the reaction, the
mixture was poured in water and acidified to рH 2. The precipiꢀ
tate was filtered off and recrystallized from EtOH.
4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazoleꢀ3ꢀcarboxaldehyde oxime
(13). A mixture of 4a (0.62 g, 2 mmol) and hydroxylamine
hydrochloride (0.21 g, 3 mmol) in 10 mL of acetic acid was
refluxed for 6 h. The solution was cooled, the precipitate was
filtered off, washed with water, and dried in air to give 0.55 g of
compound 13. M.p. 218—220 °C. 1H: 7.60—7.90 (m, 5 H, Ph);

Synthesis of 1ꢀarylꢀ4,6ꢀdinitroꢀ1Hꢀindazoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1789
8.45 (s, 1 H, CH=N); 8.62 (s, 1 H, H(5)); 8.78 (s, 1 H, H(7));
11.70 (s, 1 H, NOH).
0.14 g (19%) of compound 21. M.p. 217—218 °C. Found (%):
C, 52.21; H, 3.38. C16H13N5O6. Calculated (%): C, 51.76;
H, 3.53. 1H NMR: 2.90—3.10 (m, 2 H, CH2); 5.76 (m, 1 H,
HCNH2); 7.50—7.90 (m, 6 H, NH2, Ph); 8.30 (d, 1 H, NH2);
8.61, 8.79 (both d, each 1 H, H(5) and H(7), 4JH,H = 1.40 Hz).
13C NMR: 22.84, 44.98, 112.90, 113.70, 117.46, 124.21, 129.17,
130.57, 138.42, 140.62, 143.30, 145.81, 146.16, 172.39. MS,
m/z: 371 [М]+.
1ꢀ(4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀyl)ꢀ2ꢀ(2,4,6ꢀtrinitroꢀ
phenyl)ethanol (22). Potassium carbonate (0.14 g, 1 mmol) was
added to a suspension of TNT (0.23 g, 1 mmol) and 4a (0.32 g,
1 mmol) in 10 mL of EtOH and the mixture was stirred for 24 h
at 20 °C. The precipitate was filtered off, washed with water,
dried in air, and recrystallized from benzene to give 0.49 g of
compound 22. M.p. 204—206 °C (C6H6). Found (%): C, 46.83;
H, 2.38. C21H13N7O11. Calculated (%): C, 46.76; H, 2.43.
1H NMR: 3.85 (dd, 1 H, CH2, J = 14 Hz); 4.10 (dd, 1 H, CH2,
J = 14 Hz); 5.40 (m, 1 H, CH); 5.90 (d, 1 H, OH, J = 6.1 Hz);
7.50—7.80 (m, 3 H, Ph); 7.85 (d, 2 H, Ph, J = 7.3 Hz); 8.60 (s,
1 H, H(5)); 8.80 (s, 1 H, H(7)); 9.00 (s, 2 H, Pic). MS, m/z:
538 [M]–, 226 [C6H2(NO2)3]–.
3ꢀCyanoꢀ4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazole (14). A mixture
of 13 (3 g, 9.2 mmol) and 75 mL of acetic anhydride was reꢀ
fluxed for 6 h. After cooling the solution, the precipitate was
filtered off and washed with ethanol to give 2.46 g of compound
14. M.p. 275—277 °C (Ac2O). Found (%): C, 54.71; H, 2.14.
C14H7N5O4. Calculated (%): C, 54.38; H, 2.28. 1H NMR:
7.60—7.90 (m, 5 H, Ph); 8.95 (s, 2 H, H(5) and H(7)). 13C NMR:
112.5, 115.1, 116.0, 124.5, 130.1, 136.7, 139.7, 146.1.
3ꢀCyanoꢀ6ꢀnitroꢀ1ꢀphenylꢀ4ꢀ(2,2,3,3ꢀtetrafluoropropyloxy)ꢀ
1Hꢀindazole (16b). A mixture of nitrile 14 (0.31 g, 1 mmol),
2,2,3,3ꢀtetrafluoropropanol (0.09 mL, 1 mmol), and К2CO3
(0.14 g, 1 mmol) in 6 mL of NMP was stirred for 7 h at 80 °C.
The reaction mixture was poured in water and acidified to рH 2,
and the precipitate was filtered off and recrystallized from EtOH
to give 0.07 g of compound 16b. M.p. 198—200 °C (EtOH).
Found (%): C, 51.77; H, 2.63. C17H10F4N4O3. Calculated (%):
C, 51.79; H, 2.56. 1H NMR: 5.05 (t, 2 H, OCH2, J = 18 Hz);
6.65 (tt, 1 H, CHF2); 7.55—7.85 (m, 5 H, Ph); 7.91 (s, 1 H,
H(5)); 8.28 (s, 1 H, H(7)).
Ethyl
2ꢀcyanoꢀ3ꢀ(4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀ
Diethyl 2,6ꢀdimethylꢀ4ꢀ(4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀ
yl)ꢀ1,4ꢀdihydropyridineꢀ3,5ꢀdicarboxylate (23a). A mixture of
compound 4a (1.05 g, 3.37 mmol), ethyl acetoacetate (0.93 mL,
6.75 mmol), conc. aqueous NH3 (0.6 mL), and EtOH (15 mL)
was refluxed for 6 h. After cooling the reaction mixture, the
precipitate was filtered off and the filtrate was poured in water.
The resulting precipitate was filtered off and dried in air to give
yl)acrylate (18). A suspension of compound 4a (1 g, 3.2 mmol),
cyanoacetic ester (0.36 g, 3.2 mmol), AcOH (0.04 g), and
NH4OAc (0.025 mg) in 20 mL benzene was refluxed for 5 h with
a water trap. After cooling, the precipitate was filtered off, washed
with benzene, and dried in vacuo to give 0.6 g (46%) of comꢀ
pound 18, m.p. >300 °C (dec.). Found (%): C, 55.81; H, 3.13.
C19H13N5O6. Calculated (%): C, 56.02; H, 3.22. 1H NMR: 1.41
(t, 3 H, CH3, J = 6.57 Hz); 4.40 (q, 2 H, CH2, J = 6.57 Hz);
7.60—7.80 (m, 3 H, Ph); 7.95 (m, 2 H, Ph); 8.92 (s, 1 H);
8.98 (s, 2 H).
1
0.22 g of compound 23a. M.p. 112—114 °C. H NMR: 1.05 (t,
3
3
6 H, 2 CH3, J = 6.7 Hz); 2.25 (s, 6 H, 2 CH3); 3.95 (m, 4 H,
2 CH2); 5.60 (s, 1 H, CH); 7.50—7.70 (m, 5 H, Ph); 8.61 (s,
1 H, NH); 8.69 (s, 2 H, H(5) and H(7)).
(4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀylmethylene)malonic
acid (19). A mixture of compound 4a (1.25 g, 4 mmol), malonic
acid (0.42 g, 4 mmol), NH4OAc (0.78 g, 10 mmol), and EtOH
(40 mL) was refluxed for 5 h. The reaction mixture was cooled
and the precipitate was filtered off, washed with EtOH and
water, and dried in air to give 1.34 g (84%) of compound 19.
M.p. >300 °C (dec.). Found (%): C, 51.39; H, 2.44. C17H10N4O8.
Calculated (%): C, 51.27; H, 2.53. 1H NMR: 7.00—7.50 (m,
5 H, Ph); 8.10 (s, 1 H, CH); 8.83 (s, 1 H, H(5)); 9.01 (s, 1 H,
H(7)); 12.90 (br.s, 2 H, 2 OH). 13C NMR: 117.8, 114.5, 119.4,
124.6, 129.6, 130.8, 131.7, 134.0, 138.5, 140.4, 141.9, 143.3,
145.9, 167.6, 167.8. MS, m/z: 398 [M]+.
3ꢀ(4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀyl)acrylic acid (20).
A solution of compound 4a (1 g, 3.2 mmol), malonic acid (0.4 g,
3.8 mmol), and piperidine (0.03 mL, 0.32 mmol) in 5 mL of
pyridine was stirred for 5 h at 80—90 °C. The mixture was
cooled and the precipitate was filtered off, washed with pyriꢀ
dine, 5% HCl, and water, and dried in vacuo to give 0.5 g (44%)
of compound 20. M.p. >300 °C (dec.). Found (%): C, 54.31;
H, 3.03. C16H10N4O6. Calculated (%): C, 54.24; H, 2.85.
1H NMR: 6.75 (d, 1 H, CH, 3JH,H = 15.26 Hz); 7.50—7.70 (m,
3 H, Ph); 7.90 (m, 1 H, Ph); 8.04 (d, 1 H, CH, 3JH,H = 15.26 Hz);
8.78 (s, 1 H, H(5)); 8.84 (s, 1 H, H(7)); 12.43 (br.s, 1 H, OH).
3ꢀAminoꢀ3ꢀ(4,6ꢀdinitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀyl)propionic
acid (21). A mixture of compound 4a (0.624 g, 2 mmol), malꢀ
onic acid (0.26 g, 2.5 mmol), NH4OAc (0.48 g, 6.2 mmol), and
AcOH (20 mL) was stirred for 6 h at 100 °C. After cooling the
reaction mixture, the precipitate was filtered off, the filtrate was
poured in water, and the acid precipitated was filtered off to give
Diethyl 2,6ꢀdimethylꢀ4ꢀ[4ꢀ(cyclohexylthio)ꢀ6ꢀnitroꢀ1ꢀpheꢀ
nylꢀ1Hꢀindazolꢀ3ꢀyl]methyleneꢀ1,4ꢀdihydropyridineꢀ3,5ꢀdiꢀ
carboxylate (23b). A mixture of compound 8c (1.53 g, 4 mmol),
ethyl acetoacetate (1.1 mL, 8 mmol), conc. aqueous NH3
(0.5 mL), and EtOH (15 mL) was refluxed for 16 h. After coolꢀ
ing, the reaction mixture was poured in water and the precipiꢀ
tate was filtered off and dried in air to give 1.7 g of compound
23b. M.p. 271—272 °C. Found (%): C, 63.31; H, 6.03; S, 5.57.
C
32H36N4O6S. Calculated (%): C, 63.56; H, 6.00; S, 5.30.
1H NMR: 0.95 (t, 6 H, 2 CH3, J = 6.9 Hz); 1.30—1.90 (m,
cycloꢀC6H11); 2.32 (s, 6 H, 2 CH3); 3.60 (m, 1 H, CHS); 3.95
(m, 4 H, 2 CH2); 5.88 (s, 1 H, CH); 7.41 (m, 1 H, Ph); 7.60—7.70
(m, 4 H, Ph); 7.80 (s, 1 H, H(5)); 8.22 (s, 1 H, H(7)); 8.63
(s, 1 H, NH).
3ꢀ[4ꢀ(Cyclohexylthio)ꢀ6ꢀnitroꢀ1ꢀphenylꢀ1Hꢀindazolꢀ3ꢀ
yl]methyleneꢀ2,4ꢀpentanedione (24). A mixture of compound 4a
(1.15 g, 3 mmol), acetylacetone (0.62 mL, 6 mmol), conc. aqueꢀ
ous NH3 (0.4 mL), and EtOH (15 mL) was refluxed for 5 h.
After cooling the reaction mixture, the precipitate was filtered
off and recrystallized from EtOH to give 1 g of compound 24.
M.p. 167—169 °C (EtOH). Found (%): C, 64.23; H, 5.46;
S, 6.97. C26H25N3O4S. Calculated (%): C, 64.68; H, 5.44;
S, 6.92. 1H NMR: 1.30—1.90 and 2.00—2.30 (both m, 10 H,
SC6H11); 2.40 (s, 1 H, CH3); 2.52 (s, 1 H, CH3); 3.61 (m, 1 H,
CHS); 7.50—7.80 (m, 5 H, Ph); 8.13 (s, 1 H, H(5)); 8.36 (s,
1 H, H(7)); 8.51 (s, 1 H, CH).
4,6ꢀDinitroꢀ1ꢀphenylꢀ1Hꢀindazoleꢀ3ꢀcarboxylic acid (25).
A 30% solution of H2O2 (3 mL) was added to a solution of
compound 4a (0.624 g, 2 mmol) in 20 mL of AcOH. The mixꢀ

1790
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Starosotnikov et al.
ture was stirred for 6 h at 60 °C. After cooling to 20 °C, the
mixture was poured in water and the precipitate was filtered off
and washed with CHCl3 to give 0.48 g of compound 25. M.p.
216—219 °C. Found (%): C, 51.31; H, 2.67. C14H8N4O6. Calꢀ
culated (%): C, 51.23; H, 2.46. 1H NMR: 7.60—7.90 (m, 5 H,
Ph); 8.65 (s, 1 H, H(5)); 8.82 (s, 1 H, H(7)). 13C NMR: 112.5,
113.6, 116.1, 124.0, 129.1, 129.9, 137.3, 139.8, 141.8, 145.7,
151.9, 162.0.
2. V. M. Vinogradov, I. L. Dalinger, A. M. Starosotnikov, and
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2001, 445 [Russ.
Chem. Bull., Int. Ed., 2001, 50, 464].
3. A. M. Starosotnikov, V. M. Vinogradov, V. V. Kachala, and
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2002, 1399 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 1519].
4. V. M. Vinogradov, A. M. Starosotnikov, and S. A. Shevelev,
Mendeleev Commun., 2002, 198.
5. V. M. Rodionov and B. I. Kurtev, Izv. Akad. Nauk SSSR, Otd.
Khim. Nauk [Bull. Acad. Sci. Chem.], 1952, 113.
6. A. M. Kuvshinov, V. I. Gulevskaya, I. I. Chervin, and S. A.
Shevelev, Synthesis, 1999, 2065.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ
32261).
7. V. V. Rozhkov, A. M. Kuvshinov, and S. A. Shevelev, Izv.
Akad. Nauk, Ser. Khim., 2000, 569 [Russ. Chem. Bull., Int.
Ed., 2000, 49, 654].
References
8. A. Hantzsch, Liebigs Ann. Chem., 1882, 215, 1.
1. V. M. Vinogradov, I. L. Dalinger, A. M. Starosotnikov, and
S. A. Shevelev, Mendeleev Commun., 2000, 140.
Received April 3, 2003