Synthesis of 3-R-2-aryl-4,6-dinitroindoles and specific features of their reactions with anionic nucleophiles

Article abstract of DOI:10.1007/s11172-007-0250-6

Reaction of different anionic S-nucleophiles with 3-R-2-aryl-4,6- dinitroindoles led to a regiospecific nucleophilic substitution of the nitro group in position 4 with 6-NO₂ group remaining intact. The representatives of some peri-annulated polycyclic systems were synthesized on the basis of the substitution products.

Full text of DOI:10.1007/s11172-007-0250-6

Russian Chemical Bulletin, International Edition, Vol. 56, No. 8, pp. 1603—1607, August, 2007
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Synthesis of 3ꢀRꢀ2ꢀarylꢀ4,6ꢀdinitroindoles and specific features
of their reactions with anionic nucleophiles*
M. A. Bastrakov, A. M. Starosotnikov, V. V. Kachala, E. N. Nesterova, and S. A. Shevelevꢀ
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: shevelev@ioc.ac.ru
Reaction of different anionic Sꢀnucleophiles with 3ꢀRꢀ2ꢀarylꢀ4,6ꢀdinitroindoles led to
a regiospecific nucleophilic substitution of the nitro group in position 4 with 6ꢀNO2 group
remaining intact. The representatives of some periꢀannulated polycyclic systems were syntheꢀ
sized on the basis of the substitution products.
Key words: nitro compounds, indoles, nucleophilic substitution, nitro group.
The interest of researchers to the chemistry of indoles,
to the elaboration of new methods for the synthesis of its
derivatives and their functionalization is connected first
of all with a large number of compounds of indole series
found in the nature. Many of indole derivatives both of
the natural and manꢀmade origin have various biological
activities. Such compounds are of interest from the point
of view of preparation of their synthetic analogs as the
potential chemiotherapeutic medicines. A considerable
part of data on the synthesis and reactivity of indole deꢀ
rivatives is summarized in monograph.1
be substituted upon treatment with thiols.6 As to 2ꢀarylꢀ
4,6ꢀdinitroindoles, to date, there is no information on
substitution of the nitro group in these compounds.
We found that 2ꢀarylꢀ1ꢀmethylꢀ4,6ꢀdinitroindoles 1
without substituents in position 3 do not react with anꢀ
ionic nucleophiles even under drastic conditions. We beꢀ
lieve that this results from the low electrophilicity of these
compounds. To increase the electrophilicity of the heteroꢀ
cyclic system, it was reasonable to introduce electronꢀ
withdrawing substituents, such as CHO, CN, etc., in poꢀ
sition 3 of the indole ring.
Earlier, a preparative method for the synthesis of a
new type of substituted indoles, viz., 2ꢀarylꢀ4,6ꢀdinitroꢀ
indoles, has been developed on the basis of 2,4,6ꢀtrinitroꢀ
toluene (TNT).2 The present research work deals with
functionalization of this type of indoles through the subꢀ
stitution of nitro group upon treatment with nucleophiles
and possible subsequent annulation of the other heteroꢀ
cyclic fragments. Such an approach would have allowed
us to use 2ꢀarylꢀ4,6ꢀdinitroindoles as the basis for the
creation of new indole derivatives with potential useful
biological activity.
Earlier, we have reported the regiospecific nucleoꢀ
philic substitution of 4ꢀNO2 groups in various 4,6ꢀdiꢀ
nitrobenzoꢀannulated heterocycles (3ꢀRꢀ4,6ꢀdinitroꢀ
benzo[d]isoxazoles,3 3ꢀRꢀ1ꢀarylꢀ4,6ꢀdinitroꢀ1Нꢀindazoꢀ
les,4 4,6ꢀdinitrobenzo[b]thiophenes,5 etc.). During this,
the nitro group in position 6 remained intact both when
the excess of nucleophile was used and when the reaction
conditions were made increasingly drastic. However, in
case of highly electrophilic 3ꢀRꢀ4,6ꢀdinitrobenzo[d]isoxꢀ
azoles (R = CN and CH=NOMe), 6ꢀNO2 group can also
Indoles are well known to undergo the formylation at
position 3 under the Vilsmeier reaction conditions. The
isolated examples of such transformations for 4,6ꢀdiꢀ
nitroindoles were described earlier.7 We used a modified
procedure for the introduction of a formyl group to the
dinitroindole core, which enabled us to obtain 2ꢀarylꢀ3ꢀ
formylꢀ4,6ꢀdinitroindoles 2 in high yields (Scheme 1).
Treatment of aldehydes 2 with hydroxylamine hydrochloꢀ
ride in acetic (in case of 2a) or formic (in case of 2b)
acid led to the formation of the earlier unknown 3ꢀcyano
derivatives 3. When the reaction was carried out
with NH2OH•HCl in ethanol, oximes 4 were obtained,
whereas treatment of aldehydes 2 with arylhydrazines led
to the corresponding hydrazones 5. The yield of comꢀ
pounds 2—5 varied from 67 to 83%.
The study on interaction of 3ꢀRꢀ4,6ꢀdinitroindoles 2
and 3 with anionic Sꢀnucleophiles was carried out on
their model reaction with aromatic and aliphatic thiols.
Thus compounds 2 and 3 react with thiophenol, benzylꢀ
mercaptane, 1ꢀthioglycerol, and methyl thioglycolate in
the presence of К2СО3 in Nꢀmethylpyrrolidone (NꢀMP)
already at room temperature (Scheme 2), giving rise to
the products of substitution of the nitro group in posiꢀ
tion 4 (6a—g) in high yields (61—88%). In all cases, deꢀ
* Dedicated to Academician V. A. Tartakovsky in honor of his
75th anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1543—1547, August, 2007.
1066ꢀ5285/07/5608ꢀ1603 © 2007 Springer Science+Business Media, Inc.

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Bastrakov et al.
Scheme 1
Ar = Ph (2a, 3a, 5a,b);4ꢀClC6H4 (2b, 3b); Ar´ = Ph (5a), 4ꢀMeC6H4 (5b)
spite of the use of nucleophilic reagent in excess, no prodꢀ
ucts of substitution of 6ꢀNO2 group were observed acꢀ
cording to the Н NMR spectra of the crude reaction
and the methylеne hydrogen atoms of SCH2Ph substituꢀ
ent (for 6а and 6е) or orthoꢀprotons of SPh substituent
(for 6b) were observed. These facts allowed us to make an
unambiguous conclusion about the substitution of the very
nitro groups in position 4. For the other sulfides 6, the
evidence of substitution of 4ꢀNO2 group was obtained by
chemical methods (see below).
1
product.
Scheme 2
In the reaction of dinitroindole 2a with methyl thioꢀ
glycolate, the intermediately formed product of substituꢀ
tion of 4ꢀNO2 group under the reaction conditions unꢀ
dergoes cyclization through the addition of the acꢀ
tive methylеne unit in SCH2CO2Me substituent at the
formyl group (Scheme 3) to form a representative of the
Scheme 3
Compound
Ar
R
R´
6a
6b
6c
6d
6e
6f
Ph
Ph
Ph
CHO
CHO
CHO
CHO
CN
Bn
Ph
CH2CH(OH)CH2OH
CH2CH(OH)CH2OH
Bn
4ꢀClC6H4
Ph
Ph
4ꢀClC6H4
CN
CN
CH2CO2Me
CH2CO2Me
6g
The direction of substitution of the nitro group was
established by 1Н NMR spectroscopy (2D NOESY). For
compounds 6a,b,e, the interactions between hydrogen
atoms of the Nꢀmethyl group of indole and Н(7)
(8.4—8.5 ppm), as well as between Н(5) (7.9—8.1 ppm)

3ꢀRꢀ2ꢀPhenylꢀ4,6ꢀdinitroindoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
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periꢀannulated tricyclic heteroaromatic compounds 7 of
thiopyrano[4,3,2ꢀcd]indole series.
80—90 °С gave no periꢀannulated tricyclic derivatives
13a,b, too, resulting only in decomposition of the starting
sulfones.
The fact of formation of such a tricyclic system is a
chemical evidence of substitution of the 4ꢀNO2 group.
Compound 7 is a structural analog of the natural antiꢀ
biotic chuansinmycin 8, which has been synthesized8 by
the similar scheme, starting from methyl (3ꢀacetylindolꢀ
4ꢀyl)thioacetate (9) (Scheme 4).
Scheme 6
Scheme 4
It shows activity toward a number of gramꢀpositive
and gramꢀnegative bacteria.8
The products of substitution of the nitro group in
dinitrophenylindoles by the residue of 1ꢀthioglycerol
(6c,d) form cyclic acetals 10a,b upon treatment with cataꢀ
lytic amounts of TsOH (Scheme 5), which is another
evidence of the regiospecific substitution of the nitro
groups in position 4.
In conclusion, a series of 3ꢀRꢀ2ꢀarylꢀ4,6ꢀdinitroꢀ
indoles were synthesized; a study of their reactions with
anionic nucleophiles showed that the nitro group in posiꢀ
tion 4 is regiospecifically substituted upon treatment with
various Sꢀnucleophiles, leaving the 6ꢀNO2 group intact.
The representatives of some periꢀannulated heterocyclic
systems were synthesized on the basis of the products of
substitution of the 4ꢀNO2 group in 3ꢀRꢀ4,6ꢀdinitroꢀ2ꢀ
arylindoles.
Scheme 5
Experimental
1
Н NMR spectra were recorded on a Bruker ACꢀ200 specꢀ
trometer, 13С NMR spectra, on a Bruker AМꢀ300 spectrometer.
Chemical shifts (δ) are given from Me4Si. All the samples for
NMR spectroscopy were prepared in DMSOꢀd6. IR spectra were
recorded on a Specord Mꢀ80 spectrometer in KBr pellets. Mass
spectra were recorded on a Kratos MSꢀ30 (EI, 70 eV). The
reaction progress and the purity of compounds were monitored
by TLC on Silufol UVꢀ254 plates. Dry DMF was used for the
reactions. The other solvents were used without additional dryꢀ
ing. Compounds 1a,b were synthesized according to the proceꢀ
dure described earlier.7
Synthesis of aldehydes 2a,b (general procedure). Dinitroꢀ
indole 1a or 1b (5.75 mmol) was added to a mixture of DMF
(20 mL) and POCl3 (5.3 mL, 57.5 mmol). The mixture was
heated for 15 h at 70—75 °С. Then, the cooled mixture was
poured on ice (100 g) and treated with 58% aq. HNO3 (15 mL).
The precipitate thus formed was filtered off, the filtrate was kept
It should be noted that dinitro derivatives 2 and 3 do
not react with other anionic nucleophiles, such as NaN3,
as well as with phenol in dipolar aprotic solvents in the
presence of К2СО3: the increasingly drastic reaction conꢀ
ditions (100 °С) only cause resinification.
Attempted cyclization of sulfides 6f,g through the adꢀ
dition of the methylеne unit of SCH2CO2Me substituent
at the CN bond to form tricyclic compounds 11a,b simiꢀ
larly to cyclization of indazole4b and benzo[d]isoxazole6
derivatives failed. In order to obtain compounds with the
more active methylеne fragment, sulfides 6f,g were oxiꢀ
dized to the corresponding sulfones 12a,b (Scheme 6).
However, treatment of the latter with К2СО3 in NꢀMP at

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Bastrakov et al.
for 16 h. The precipitate formed from the filtrate was filtered off
and added to 20% aq. NaOH (200 mL). The mixture was reꢀ
fluxed for 1 h, cooled, the precipitate was filtered off and dried
in air.
1ꢀMethylꢀ4,6ꢀdinitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀcarbaldehyde
Nꢀ(4ꢀmethylphenyl)hydrazone (5b). The yield was 0.55 g (82%),
m.p. 230—233 °С. Found (%): C, 64.59; H, 4.72; N, 16.03.
C23H19N5O4 Calculated (%): C, 64.33; H, 4.46; N, 16.31.
1H NMR, δ: 2.85 (s, 3 Н, СМе); 3.85 (s, 3 Н, NМе); 6.70 (d,
2 Н, 4ꢀМеC6H4, JH—H = 10 Hz); 6.95 (d, 2 Н, 4ꢀМеC6H4,
3JH—H = 10 Hz); 7.60—7.70 (m, 5 H, Ph); 7.80, 8.50, 8.95 (all s,
1 H each); 9.95 (s, 1 H, NH).
1ꢀMethylꢀ4,6ꢀdinitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀcarbaldehyde
(2a). The yield was 1.44 g (77%), m.p. 224—226 °C (cf. Ref. 7:
3
1
m.p. 225—228 °С). H NMR, δ: 3.91 (s, 3 Н, Ме); 7.52—7.89
(m, 5 H, Ph); 8.60 (s, 1 Н, Н(5)); 9.03 (s, 1 H, H(7)); 10.65 (s,
1 Н, СНО).
Synthesis of sulfides 6a—g (general procedure). Potassium
carbonate (3 mmol) and the corresponding thiol (3 mmol)
(in case of 1ꢀthioglycerol, thiol (4.5 mmol) and К2СО3 (4.5 mol))
were added to a solution of compounds 2a,b or 3a,b (1.5 mmol)
in NꢀMP (7 mL). The reaction mixture was stirred for 24 h at
20 °С, poured in water (50 mL), acidified with conc. HCl
to pH = 3, the precipitate formed was filtered off, dried in air,
and washed with hot EtOH; in case of oily products, they were
extracted with ethyl acetate (2×50 mL), dried with Na2SO4, and
the solvent was evaporated.
4ꢀBenzylsulfanylꢀ1ꢀmethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ1Нꢀindoleꢀ3ꢀ
carbaldehyde (6a). The yield was 0.47 g (79%), m.p. 185—190 °С.
Found (%): С, 68.87; H, 4.65; N, 6.80. С23H18N2O3S. Calcuꢀ
lated (%): С, 68,64; H, 4,51; N, 6,96. 1H NMR, δ: 3.70 (s, 3 Н,
Ме); 4.50 (s, 2 H, CH2); 7.20—7.50 (m, 5 H, Ph); 8.12 (s, 1 H,
H(5)); 8.48 (s, 1 H, H(7)); 10.31 (s, 1 Н, СНО).
1ꢀMethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ4ꢀphenylsulfanylꢀ1Нꢀindoleꢀ3ꢀ
carbaldehyde (6b). The yield was 0.46 g (81%), m.p. 198—201 °C.
Found (%): С, 68.24; H, 4.18; N, 7.31. С22H16N2O3S. Calcuꢀ
lated (%): С, 68.02; H, 4.15; N, 7.21. 1H NMR, δ: 3.70 (s, 3 Н,
Ме); 7.58 (m, 3 H, Ph); 7.64 (m, 2 H, Ph); 7.80 (s, 1 Н, Н(5));
8.50 (s, 1 H, H(7)); 10.30 (s, 1 Н, СНО).
4ꢀ(2,3ꢀDihydroxypropylsulfanyl)ꢀ1ꢀmethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ
1Hꢀindoleꢀ3ꢀcarbaldehyde (6c). The yield was 0.45 g (79%), m.p.
98—102 °С. Found (%): C, 59.37; H, 4.49; N, 7.01.
C19H18N2O5S. Calculated (%): C, 59.06; H, 4.70; N, 7.25.
1H NMR, δ: 3.10, 3.50 (both m, 2 Н each); 3.70 (s, 3 Н, Ме);
4.80, 5.20 (both br.s, 1 H each, ОH); 7.60—7.80 (m, 5 H, Ph);
8.10 (s, 1 H, H(5)); 8.40 (s, 1 H, H(7)). IR, ν/cm–1: 2924, 2872,
1508, 1452, 1392, 1356, 1328, 1156, 1092, 952, 880, 760,
748, 708.
2ꢀ(4ꢀChlorophenyl)ꢀ1ꢀmethylꢀ4,6ꢀdinitroꢀ1Hꢀindoleꢀ3ꢀcarbꢀ
aldehyde (2b). The yield was 1.6 g (82%), m.p. 244—246 °C.
Found (%): C, 53.31; H, 2.99; N, 11.84; C16H10ClN3O5. Calcuꢀ
lated (%): C, 53.42; H, 2.80; N, 11.68. 1H NMR, δ: 3.89 (s, 3 Н,
Ме); 7.65—7.85 (m, 4 H, 4ꢀClC6H4); 8.65 (s, 1 Н, Н(5)); 9.05
(s, 1 H, H(7)); 10.63 (s, 1 Н, СНО).
1ꢀMethylꢀ4,6ꢀdinitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀcarbоnitrile
(3а). A solution of aldehyde 1а (1.3 g, 4 mmol) and NH2OH•
•HCl (0.42 g, 6 mmol) in АсОН (7 mL) was refluxed for 6 h,
cooled and poured in water (50 mL). The precipitate formed
was filtered off and dried in air to obtain compound 3а (1.0 g,
77%), m.p. 255—259 °C. Found (%): C, 59.37; H, 3.23; N, 17.49.
C16H10N4O4. Calculated (%): C, 59.63; H, 3.13; N, 17.38.
1H NMR, δ: 3.95 (s, 3 Н, Ме); 7.65—7.80 (m, 5 Н, Ph); 8.85 (s,
1 H, H(5).); 9.20 (s, 1 H, H(7)). IR, ν/cm–1: 2300, 1664, 1552,
1536, 1516, 1408, 1368, 1296, 1232, 1140, 1020, 968, 928, 876,
824, 788, 756, 688.
2ꢀ(4ꢀChlorophenyl)ꢀ1ꢀmethylꢀ4,6ꢀdinitroꢀ1Hꢀindoleꢀ3ꢀ
carbоnitrile (3b). A solution of aldehyde 2b (0.54 g, 1.5 mmol)
and NH2OH•HCl (0.16 g, 2.25 mmol) in 95—98% aq. HCOOH
(7 mL) was refluxed for 6 h, cooled and poured in water (50 mL)).
The precipitate formed was filtered off and refluxed in Ас2О
(5 mL) for 4 h. The solvent was evaporated, the residue was
washed with water and dried in air to obtain compound 3b
(0.2 g, 67%), m.p. 231—236 °C. Found (%): C, 54.06; H, 2.32;
N, 15.39. C16H9ClN4O4. Calculated (%): C, 53.87; H, 2.54;
1
N, 15.71. H NMR, δ: 4.03 (s, 3 Н, Ме); 7.71—7.89 (m, 4 Н,
4ꢀClC6H4); 8.80 (s, 1 H, H(5)); 9.2 (s, 1 H, H(7)). IR, ν/cm–1
:
2232, 1508, 1428, 1296, 1060, 828, 716.
1ꢀMethylꢀ4,6ꢀdinitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀcarbaldehyde
oxime (4). A mixture of aldehyde 2а (0.325 g, 1 mmol),
NH2OH•HCl (0.07 g, 1 mmol), and EtOH (10 mL) was reꢀ
fluxed for 30 min, then cooled, the precipitate was filtered off to
obtain compound 4 (0.24 g, 71%), m.p. 225—228 °C. Found (%):
C, 56.19; H, 3.38; N, 16.79. C16H12N4O5. Calculated (%):
C, 56.47; H, 3.55; N, 16.46. H NMR, δ: 3.89 (s, 3 Н, Ме);
7.52—7.54 (m, 5 Н, Ph); 8.0 (s, 1 H, СН); 8.59 (s, 1 H, Н(5));
9.0 (s, 1 H, Н(7)); 11.01 (s, 1 H, ОН).
2ꢀ(4ꢀChlorophenyl)ꢀ4ꢀ(2,3ꢀdihydroxypropylsulfanyl)ꢀ1ꢀ
methylꢀ6ꢀnitroꢀ1Hꢀindoleꢀ3ꢀcarbaldehyde (6d). The yield
was 0.45 g (71%), m.p. 100—105 °С. Found (%): C, 54.50;
H, 3.89; N, 6.87. C19H17ClN2O5S. Calculated (%): C, 54.22;
1
H, 4.07; N, 6.66. H NMR, δ: 3.10, 3.50 (both m, 2 Н each);
1
3.70 (s, 3 Н, Ме); 4.80, 5.20 (both br.s, 1 H each, ОH);
7.50—7.80 (m, 4 H, 4ꢀClC6H4); 8.10 (s, 1 H, H(5)); 8.50
(s, 1 H, H(7)).
Synthesis of hydrazones 5a,b (general procedure). A mixture
of aldehyde 2a (0.49 g, 1.5 mmol), the corresponding arylꢀ
hydrazine hydrochloride (1.5 mmol) and EtOH (10 mL) was
refluxed for 30 min. Then it was cooled, the precipitate formed
was filtered off and dried in air.
1ꢀMethylꢀ4,6ꢀdinitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀcarbaldehyde
Nꢀphenylhydrazone (5a). The yield was 0.52 g (83%), m.p.
220—225 °С. Found (%): C, 63.37; H, 4.28; N, 17.09.
4ꢀBenzylsulfanylꢀ1ꢀmethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ3ꢀ
carbоnitrile (6e). The yield was 0.44 g (75%), m.p. 187—190 °С.
Found (%): C, 68.91; H, 4.49; N, 10.80. C23H17N3O2S. Calcuꢀ
lated (%): C, 69.15; H, 4.29; N, 10.52. 1H NMR, δ: 3.85 (s, 3 Н,
Ме); 4.50 (s, 2 H, CH2); 7.20—7.50, 7.60—7.80 (both m,
5 H each, Ph); 8.10 (s, 1 H, H(5)); 8.50 (s, 1 H, H(7)).
Methyl 2ꢀ[(3ꢀcyanoꢀ1ꢀmethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ
4ꢀyl)sulfanyl]acetate (6f). The yield was 0.47 g (88%), m.p.
205—206 °С. Found (%): C, 59.55; H, 3.79; N, 11.27.
С19H15N3O4S. Calculated (%): C, 59.83; H, 3.96; N, 11.02.
1H NMR, δ: 3.70, 3.90 (both s, 3 Н each, Ме); 4.20 (s,
2 H, CH2); 7.60—7.80 (m, 5 H, Ph); 8.00 (s, 1 H, H(5)); 8.60
(s, 1 H, H(7)).
C22H17N5O4. Calculated (%): C, 63.61; H, 4.12; N, 16.86.
3
1H NMR, δ: 3.85 (s, 3 Н, Ме); 6.65 (t, 1 Н, Ph, JH—H
=
3
8.8 Hz); 6.80 (d, 2 Н, Ph, JH—H = 8.9 Hz); 7.23 (t, 2 Н, Ph,
3JH—H = 8.8 Hz); 7.62—7.70 (m, 5 H, Ph); 7.79, 8.50, 8.95
(all s, 1 H each); 10.05 (s, 1 H, NH).

3ꢀRꢀ2ꢀPhenylꢀ4,6ꢀdinitroindoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1607
Methyl 2ꢀ[2ꢀ(4ꢀchlorophenyl)ꢀ3ꢀcyanoꢀ1ꢀmethylꢀ6ꢀnitroꢀ
1Hꢀindoleꢀ4ꢀyl)sulfanyl]acetate (6g). The yield was 0.42 g (61%),
m.p. 215—216 °С. Found (%): C, 55.12; H, 3.07; N, 10.31.
С19H14ClN3O4S. Calculated (%): C, 54.88; H, 3.39; N, 10.10.
1H NMR, δ: 3.65, 3.90 (both s, 3 Н each, Ме); 4.20 (s, 2 H,
CH2); 7.70—7.80 (m, 4 H, 4ꢀClC6H4); 8.00 (s, 1 H, H(5)); 8.60
(s, 1 H, H(7)).
(50 mL). The precipitate formed was filtered off, washed with
hot EtOH (5 mL) and dried in air.
Methyl 2ꢀ[(3ꢀcyanoꢀ1ꢀmethylꢀ6ꢀnitroꢀ2ꢀphenylꢀ1Hꢀindoleꢀ
4ꢀyl)sulfonyl]acetate (12a). The yield was 0.12 g (20%), m.p.
232—236 °С. Found (%): C, 57.97; H, 4.17; N, 7.02.
C20H16N2O6S. Calculated (%): C, 58.25; H, 3.91; N, 6.79.
1H NMR, δ: 3.60, 4.00 (both s, 3 Н each, Ме); 4.90 (s, 2 Н,
СН2); 7.65—7.80 (m, 5 H, Ph); 8.60 (s, 1 H, H(5)); 9.15
(s, 1 H, H(7)).
Methyl 2ꢀ[2ꢀ(4ꢀchlorophenyl)ꢀ3ꢀcyanoꢀ1ꢀmethylꢀ6ꢀnitroꢀ
1Hꢀindoleꢀ4ꢀyl]sulfonylacetate (12b). The yield was 0.34 g (58%),
m.p. 173—177 °С. Found (%): C, 54.11; H, 3.74; N, 6.61.
C20H15ClN2O6S. Calculated (%): C, 53.76; H, 3.38; N, 6.27.
1H NMR, δ: 3.60, 4.00 (both s, 3 Н each, Ме); 4.90 (s, 2 Н,
СН2); 7.70—7.90 (m, 4 H, 4ꢀClC6H4); 8.60 (s, 1 H, H(5)); 9.15
(s, 1 H, H(7)).
Methyl
5ꢀmethylꢀ7ꢀnitroꢀ4ꢀphenylꢀ5Hꢀthiopyraꢀ
no[4.3.2ꢀcd]indoleꢀ2ꢀcarboxylate (7). A mixture of aldehyde 2a
(0.395 g, 1.2 mmol), methyl thioglycolate (0.17 mL, 3.6 mmol),
К2СО3 (0.5 g, 3.6 mmol), and NꢀMP (10 mL) was stirred for
24 h at 60 °С under argon atmosphere. The reaction mixture
was poured in water and acidified to рН = 2. The precipitate was
filtered off, dried and chromatographed on a column (SiO2
with CHCl3 as the eluent). The yield was 0.25 g (56%), m.p.
205—211 °С. Found (%): C, 62.16; H, 4.49; N, 7.95.
C19H16N2O4S. Calculated (%): C, 61.94; H, 4.38; N, 7.60.
1H NMR, δ: 3.65, 3.70 (both s, 3 Н each, Ме); 7.20 (s, 1 Н,
СН); 7.40 (s, 1 H, H(5)); 7.50—7.70 (m, 5 H, Ph); 8.00 (s, 1 H,
H(7)). IR, ν/cm–1: 1676, 1568, 1476, 1332, 1308, 1220, 1188,
1080, 1004, 836, 744, 716, 676, 1348, 1264, 1136, 1092, 1028,
988, 948, 904, 884, 856, 800, 764, 744.
Synthesis of compounds 10a,b (general procedure). A soluꢀ
tion of the corresponding sulfide (1 mmol) and TsOH (50 mg) in
toluene (35 mL) was refluxed with the DeanꢀStark trap for 14 h.
The precipitate formed after cooling was filtered off. The filtrate
was concentrated, the residue was chromatographed on a column
(SiO2 with CHCl3 as the eluent).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ
00414).
References
1. R. J. Sundberg, Indoles, Academic Press, SanꢀDiego, 1996.
2. V. V. Rozhkov, A. M. Kuvshinov, V. I. Gulevskaya, I. I.
Chervin, and S. A. Shevelev, Synthesis, 1999, 2065.
3. 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].
4. (a) V. M. Vinogradov, A. M. Starosotnikov, and S. A. Shevelev,
Mendeleev Commun., 2002, 198; (b) A. M. Starosotnikov, V. V.
Kachala, A. V. Lobach, V. M. Vinogradov, and S. A. Shevelev,
Izv. Akad. Nauk, Ser. Khim., 2003, 1690 [Russ. Chem. Bull.,
Int. Ed., 2003, 52, 1782]; (с) A. M. Starosotnikov, A. V.
Lobach, and S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim.,
2004, 557 [Russ. Chem. Bull., Int. Ed., 2004, 53, 584].
5. I. L. Dalinger, T. I. Cherkasova, and S. A. Shevelev, Tetraꢀ
hedron Lett., 2001, 42, 8539.
13ꢀMethylꢀ10ꢀnitroꢀ14ꢀphenylꢀ3,16ꢀdioxaꢀ7ꢀthiaꢀ13ꢀazaꢀ
tetracyclo[6.6.1.12,5.012,15]hexadecaꢀ1(14),8(15),9,11ꢀtetraene
(10а). The yield was 0.2 g (50%), m.p. 250—260 °С. Found (%):
C, 62.22; H, 4.70; N, 7.89. C19H16N2O4S. Calculated (%):
1
C, 61.94; H, 4.38; N, 7.60. H NMR, δ: 3.10 (m, 2 Н, СН2);
3.70 (s, 3 Н, Me); 3.90 (m, 1 Н); 4.45 (d, 1 Н, J = 9.8 Hz); 4.60
(br.s, 1 Н); 5.80 (s, 1 Н); 7.45—7.70 (m, 5 H, Ph); 8.15 (s, 1 H,
H(5)); 8.55 (s, 1 H, H(7)).
14ꢀ(4ꢀChlorophenyl)ꢀ13ꢀmethylꢀ10ꢀnitroꢀ3,16ꢀdioxaꢀ7ꢀthiaꢀ
13ꢀazatetracyclo[6.6.1.12,5.012,15]hexadecaꢀ1(14),8(15),9,11ꢀ
tetraene (10b). The yield was 0.2 g (47%), m.p. 252—256 °С.
Found (%): C, 56.37; H, 3.52; N, 7.19. C19H15ClN2O4S. Calꢀ
6. A. M. Starosotnikov, A. V. Lobach, Yu. A. Khomutova, and
S. A. Shevelev, Izv. Akad. Nauk, Ser. Khim., 2006, 523 [Russ.
Chem. Bull., Int. Ed., 2006, 55, 543].
7. V. V. Rozhkov, A. M. Kuvshinov, and S. A. Shevelev, Heteroꢀ
cyclic Commun., 2000, 6, 525.
1
culated (%): C, 56.65; H, 3.75; N, 6.95. H NMR, δ: 3.10 (m,
2 Н, СН2); 3.70 (s, 3 Н, Me); 3.90 (m, 1 Н); 4.40 (d, 1 Н, J =
9.7 Hz); 4.60 (br.s, 1 Н); 5.80 (s, 1 Н); 7.55, 7.70 (both d, 4 H,
4ꢀClC6H4, J = 9.6 Hz); 8.15 (s, 1 H, H(5)); 8.50 (s, 1 H, H(7)).
Synthesis of sulfones 12a,b (general procedure). A 30% soluꢀ
tion of H2O2 (1.0 mL) was added dropwise to a solution of the
corresponding sulfide (1.3 mmol) in CF3CO2H (10 mL). The
mxture was stirred for 15 h at 20 °С, then poured in water
8. A. P. Kozikovski, M. N. Greco, and J. P. Springer, J. Am.
Chem. Soc., 1982, 104, 7622.
Received June 22, 2007