Synthesis of a novel tetracyclic pyrido[3',2':4,5]thieno[3,2-b]indole system

Full text of DOI:10.1007/s10593-013-1226-0

Chemistry of Heterocyclic Compounds, Vol. 48, No. 12, March, 2013 (Russian Original Vol. 48, No. 12, December, 2012)
SYNTHESIS OF A NOVEL TETRACYCLIC
PYRIDO[3',2':4,5]THIENO[3,2-b]INDOLE SYSTEM
E. A. Kanishcheva1, V. K. Vasilin1*, D. R. Kasimova1,
T. A. Stroganova1, and G. D. Krapivin1
Keywords: 3-aminothieno[2,3-b]pyridines, azides, pyrrole, condensed system, thermolysis.
The thermal decomposition of aromatic azides is one of the widely used methods in organic synthesis
for the formation of pyrrole-containing condensed systems. This method has been used for the preparation of
such heterocyclic systems as indolopyridocarbazolones [1], carbazoles [2], indoloisoquinolines [3], including
the alkaloids cryptotackieine and cryptosanguinolentine [4, 5], pyrazino[3,4]indoles [6, 7], pyrimidino[5,4-b]indol-
ones [8], dinitroindoles [9] and furopyrroles [10, 11], benzothienoindoles [12], and thieno- and pyrrolo-
containing -carboline analogs [13].
Within the framework of studying the synthetic potential of 3-aminothieno[2,3-b]pyridine derivatives,
we report in this work the results of the synthesis of the novel tetracyclic pyrido[3',2':4,5]thieno[3,2-b]indole
system via thermolysis of 2-aryl-3-azidothieno[2,3-b]pyridines.
The 3-azido-2-(4-nitrophenyl)thienopyridines 2a,b were prepared from the corresponding amines 1a,b
in 92 and 90% yield by the successive reactions given below.
R
+
N
NH2
R
N
–
N
HSO4
NaNO2
NO2
NO2
H2SO4
AcOH
S
1a,b
Me
N
S
Me
R
N
H
N
R
N3
NO2
m-Xylene
NaN3
NO2

S
2a,b
S
Me
Me
N
3a,b
a R = Me, b R = H
The thermal decomposition of azides 2a,b was carried out by refluxing their solutions in m-xylene for
0.5-1.0 h. The yields of products 3a,b were 85 and 81%, respectively.
_______
*To whom correspondence should be addressed, e-mail: vasvk@mail.ru.
1Kuban State University of Technology, 2 Moskovskaya St., Krasnodar 350072, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 2005-2008, December, 2012.
Original article submitted November 11, 2012.
0009-3122/13/4812-1883©2013 Springer Science+Business Media New York
1883

IR spectra were recorded on a Perkin-Elmer Spectrum II instrument using an ATR accessory. The
1H and 13C NMR spectra were recorded on Agilent 400-MR (400 and 100 MHz, respectively) and Bruker AM-
300 (300 and 75 MHz, respectively) instruments using DMSO-d6 with TMS as internal standard. Mass spectra
were recorded on a Kratos MS-30 instrument using EI ionization (70 eV). Melting points were determined on a
Stuart SMP 30 instrument and were not corrected. TLC was performed on Silufol UV-254 and Sorbfil plates
(Sorbpolymer Co. Ltd.) using PhMe–EtOH (20:3) as eluent and visualized using iodine and bromine vapors.
The starting 3-aminothienopyridines 1a,b were prepared via the reaction of the corresponding
3-cyanopyridine-2-thiones with 4-nitrobenzyl bromide in the presence of aqueous KOH solution using the
method reported in [14].
4,6-Dimethyl-2-(4-nitrophenyl)thieno[2,3-b]pyridin-3-amine (1a). Yield 93%. Red-orange needles.
Mp 222-224°C. IR spectrum, , cm-1: 3473, 3440, 3362, 3340, 1584, 1544, 1521, 1502, 1448, 1433, 1382,
1329, 1311, 1261, 1185, 1106, 1069, 1030, 967, 847, 750. 1H NMR spectrum (300 MHz), , ppm (J, Hz): 2.52
(3H, s, CH3); 2.77 (3H, s, CH3); 5.42 (2Н, br. s, NH2); 6.99 (1H, s, Н-5); 7.78 (2Н, d, J = 9.0, Н-2,6 Ar); 8.26
(2Н, d, J = 9.0, Н-3,5 Ar). Mass spectrum, m/z (Irel, %): 301 [M+2Н]+ (12), 300 [M+Н]+ (17), 299 [M]+ (100),
282 (8), 269 (9), 253 (13), 220 (6), 205 (11), 177 (6), 132 (7), 107 (7), 78 (5), 59 (8), 43 (12). Found, %:
C 60.23; H 4.28; N 14.01. C15H13N3O2S. Calculated, %: C 60.19; H 4.38; N 14.04.
6-Methyl-2-(4-nitrophenyl)thieno[2,3-b]pyridin-3-amine (1b). Yield 89%. Bright-orange powder.
Mp 229-231°C. IR spectrum, , cm-1: 3318, 3231, 1629, 1589, 1566, 1529, 1500, 1391, 1326, 1285, 1258,
1
1186, 1105, 1062, 952, 849, 821, 750. H NMR spectrum (400 MHz), , ppm (J, Hz): 2.53 (3H, s, CH3); 6.19
(2Н, br. s, NH2); 7.22 (1H, d, J = 8.3, Н-5); 7.74 (2Н, d, J = 9.0, Н-2,6 Ar); 8.14 (2Н, d, J = 9.0, Н-3,5 Ar); 8.29
(1H, d, J = 8.3, Н-4). Mass spectrum, m/z (Irel, %): 286 [M+Н]+ (18), 285 [M]+ (100), 255 (5), 239 (7), 238 (4),
224 (8), 206 (6), 195 (5), 121 (9), 119 (8), 105 (5), 91 (5), 77 (7), 69 (10). Found, %: C 58.88; H 3.78; N 14.75.
C14H11N3O2S. Calculated, %: C 58.93; H 3.89; N 14.73.
Synthesis of 3-Azidothieno[2,3-b]pyridines 2a,b (General Method). Conc. H2SO4 (1 ml, 17 mmol)
was added with stirring to a solution of the 3-aminothienopyridine 1a,b (33 mmol) in glacial acetic acid
(100 ml). The mixture obtained was cooled to +12°C, and a solution of NaNO2 (3.5 g, 50 mmol) in water (3 ml)
was added. The mixture was stirred for 15 min, the excess NaNO2 was neutralized using urea, and a solution of
NaN3 (3.3 g, 50 mmol) in water (3 ml) was added. After 15 min, the mixture was poured into water (300 ml).
The precipitated crystals were separated by filtration, thoroughly washed with water, and dried in a vacuum
1
desiccator. The synthesized azides 2a,b are unstable materials and their characterization by H NMR
spectroscopy and elemental analysis was hindered by decomposition. The thermolysis stage of the obtained
azides 2a,b was carried out immediately following their preparation without additional purification.
3-Azido-4,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-b]pyridine (2a). Yield 9.87 g (92%). Red powder.
Mp 157-159°C (decomp.). IR spectrum, , cm-1: 2109, 1592, 1521, 1374, 1341, 1318, 1267, 1200, 1108, 1023,
1008, 962, 856, 842, 749, 694.
3-Azido-6-methyl-2-(4-nitrophenyl)thieno[2,3-b]pyridine (2b). Yield 9.23 g (90%). Red crystals. Mp
151-152°C (decomp.). IR spectrum, , cm-1: 2115, 1589, 1575, 1556, 1504, 1477, 1438, 1372, 1340, 1256,
1227, 1154, 1117, 1105, 1034, 939, 855, 844, 818, 751.
Thermolysis of Compounds 2a,b (General Method). A solution of azide 2a,b (30 mmol) in
anhydrous m-xylene (100 ml) was refluxed for 0.5-1.0 h until full conversion of the starting compound. The
reaction mixture was evaporated at reduced pressure to one third volume and left to crystallize. The precipitated
crystals were separated by filtration, washed with petroleum ether, and recrystallized from DMF to give
compounds 3a,b.
2,4-Dimethyl-7-nitro-5H-pyrido[3',2':4,5]thieno[3,2-b]indole (3a). Yield 7.58 g (85%). Red needles.
Mp 322-323°C. IR spectrum, , cm-1: 3599, 3331, 1645, 1612, 1548, 1507, 1479, 1436, 1378, 1337, 1311,
1296, 1239, 1191, 1065, 883, 808, 749, 730. 1H NMR spectrum (400 MHz), , ppm (J, Hz): 2.56 (3H, s, CH3);
2.83 (3H, s, CH3); 7.18 (1H, s, Н-3); 7.91 (1Н, d, 3J = 9.1, Н-9), 8.00 (1Н, dd, 3J = 9.1, 4J = 2.0, Н-8), 8.46 (1Н,
d, J = 2.0, Н-6); 12.22 (1Н, br. s, NH). 13C NMR spectrum (100 MHz), , ppm: 19.9; 24.2; 109.4; 112.1; 119.1;
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119.2; 121.4; 126.3; 139.4; 139.7; 141.7; 143.4; 156.8; 164.4. Mass spectrum, m/z (Irel, %): 299 [M+2Н]+ (12),
298 [M+Н]+ (25), 297 (100) [M]+, 267 (96), 252 (18), 251 (91), 250 (30), 249 (11), 239 (11), 235 (12), 224
(18), 211 (11), 209 (18), 178 (10), 164 (20), 139 (11), 119 (11), 101 (16), 98 (12), 91 (25), 77 (12), 76 (15), 75
(13), 69 (30), 65 (10), 63 (34), 51 (24), 45 (20), 43 (57), 42 (27), 41 (23). Found, %: C 60.71; H 3.62; N 14.07.
C15H11N3O2S. Calculated, %: C 60.59; H 3.73; N 14.13.
2-Methyl-7-nitro-5H-pyrido[3',2':4,5]thieno[3,2-b]indole (3b). Yield 6.88 g (81%). Bright-orange
needles. Mp 331-332°C. IR spectrum, , cm-1: 3605, 3318, 1654, 1616, 1577, 1566, 1499, 1474, 1444, 1381,
1
1326, 1306, 1289, 1159, 1065, 997, 934, 875, 808, 748. H NMR spectrum (300 MHz), , ppm (J, Hz): 2.62
(3H, s, CH3); 7.37 (1H, d, J = 8.1, Н-3); 7.91 (1H, d, J = 9.4, H-9); 7.96 (1Н, dd, 3J = 9.4, 4J = 2.1, Н-8), 8.32
(1Н, d, J = 8.1, Н-4); 8.43 (1Н, d, J = 2.1, Н-6); 12.37 (1Н, br. s, NH). 13C NMR spectrum (75 MHz), , ppm:
24.4, 109.3, 112.3, 115.1, 118.8, 119.4, 120.3, 126.8, 129.4, 138.1, 139.7, 143.5, 157.0, 161.5. Mass spectrum,
m/z (Irel, %): 284 [M+Н]+ (16), 283 [M]+ (100), 253 (30), 238 (11), 237 (62), 210 (5), 118 (6), 105 (8), 91 (8),
69 (12), 63 (6), 44 (24), 40 (7). Found, %: C 59.54; H 3.13; N 14.77. C14H9N3O2S. Calculated, %: C 59.35;
H 3.20; N 14.83.
This work was carried out with the support of the Ministry of Education and Science of the Russian
Federation (state contract Nos. 14.740.11.1187 and 14B37.21.0829)
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