C. G. Hızlıateş and S. Gülle
Vol 000
100°C for 30 min. Then the reaction mixture was poured
into water (100 mL) and extracted with ethyl acetate
(300 mL). The organic extracts were washed with
sodium bicarbonate (5%) and brine (5%) solutions and
dried over anhydrous magnesium sulfate. The solvent
was removed under reduced pressure, and the
crude product was purified by column chromatography
using silica gel, ethyl acetate/hexane (1:1). The solvents
were evaporated, and the residue was recrystallized
from methanol to afford nitrile 7 [26] (400 mg, 55%);
4.0 Hz), 7.28 (d, 2H, J = 8.4 Hz), 7.32–7.39 (m, 2H),
7.76 (d, 2H, J = 8.0 Hz), 8.14–8.19 (m, 2H); 13C-NMR
(DMSO-d6): 17.3, 21.5, 24.2, 28.5, 42.6, 114.2, 116.5,
119.8, 121.3, 125.4, 125.5, 125.9, 127.3 (2C), 131.0
(2C), 134.6, 135.5, 146.7, 152.1, 193.6; HRMS (ESI+):
Calcd for C21H18N2SO3 ([M + H]+) 378.2247. Found:
378.2241.
Synthesis of hexahydropyrido[3,2-c]carbazoles and
hexahydropyrrolo[3,2-c]carbazoles.
A
solution of
compounds 7, 8, 11, and/or 12 (1.5mmoles) in ethanol
(25mL) was hydrogenated at room temperature for 36h at
100psi in the presence of Raney Ni (0.50mmoles). The
catalyst was removed by filtration through Celite (Merck),
and the solvent was removed under reduced pressure.
Then, the residue was chromatographed using silica gel
and ethyl acetate/hexane (1:1). The solvent was removed,
and then the product was recrystallized from ethyl ether to
yield hexahydropyrido[3,2-c]carbazoles (9a and 9b) and
mp: 221°C.
2-(4-Oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl)acetonitrile (11).
To a solution of 10 (5.0g, 23.8mmoles) in tetrahydrofuran
(50mL, 90%), a solution of 2,3-dichloro-5,6-dicyano-p-
benzoquinone (10.8g, 47.6mmoles) in tetrahydrofuran
(25mL) was added dropwise at 0°C under nitrogen
atmosphere. The reaction mixture was stirred for 4h at
room temperature, then the solution was poured into
sodium hydroxide solution (500mL, 10%) and extracted
with ethyl acetate. The organic layer was dried with
anhydrous magnesium sulfate, and the solvent was
removed. The residue was purified by chromatography
using silica gel and ethyl acetate/hexane (1:1). After the
solvent was evaporated, the product was recrystallized
from methanol to afford oxonitrile 11 (3.20g, 60%); mp:
125°C; IR (KBr, νmax, cmꢀ1): 3238 (NH), 2938 (CH),
2246 (CN), 1619 (C¼O); 1H NMR (DMSO-d6): δ
1.96–2.08 (m, 1H) , 2.30–2.34 (m, 1H), 2.78–2.90
(m, 2H), 2.96 (dd, 1H, J = 15.2 and 4.4 Hz), 3.06–3.14
(m, 1H), 3.18 (dd, 1H, J =15.2 and 4.0Hz), 7.12–7.18
(m, 2H), 7.40 (d, 1H, J= 8.0 Hz), 7.93 (d, 1H, J=8.0Hz),
11.93 (s, 1H); 13C-NMR (DMSO-d6): 17.8, 22.7, 29.2,
42.8, 111.4, 112.1, 120.2, 120.5, 122.2, 123.1, 124.9,
136.7, 152.8, 191.4; HRMS (ESI+): Calcd for C14H12N2O
hexahydropyrrolo[3,2-c]carbazoles (13a and 13b).
3,4,4a,5,6,7-Hexahydro-2H-pyrido[3,2-c]carbazole (9a).
Yield: 165mg, 49%; mp: 227°C; IR (KBr, νmax, cmꢀ1):
1
3227 (NH), 2950 (CH), 1620 (C¼N); H-NMR (DMSO-
d6): δ 1.24–1.32 (m, 1H), 1.41–1.48, (m 1H), 1.53–1.60
(m, 1H), 2.11–2.24 (m, 2H), 2.30–2.37 (m, 1H),
2.64–2.74 (m, 3H), 2.57–2.64 (m, 1H), 3.92 (dd, 1H,
J=15.2 and 8.0Hz), 7.08–7.15 (m, 2H), 7.38 (d, 1H,
J=7.6Hz), 7.90 (d, 1H, J=7.6Hz), 11.27 (s, 1H); 13C-
NMR (DMSO-d6): 23.20, 25.62, 28.67, 30.29, 46.90,
59.51, 107.62, 111.72, 120.15, 121.03, 121.87, 124.52,
136.82, 146.72, 169.84; HRMS (ESI+): Calcd for
C15H16N2 ([M+H]+) 224.3010. Found: 224.3002.
7-Tosyl-3,4,4a,5,6,7-hexahydro-2H-pyrido[3,2-c]carbazole (9b).
Yield: 130mg, 55%; mp: 205°C; IR (KBr, νmax, cmꢀ1):
2930 (CH), 1626 (C¼N); 1H-NMR (DMSO-d6):
δ
1.26–1.34 (m, 1H), 1.57–1.64 (m, 2H), 1.65–1.71 (m, 1H),
1.82–1.92 (m, 1H), 2.05–2.09 (m, 1H), 2.30 (s, 3H), 2.32
(m, 1H), 3.03–3.12 (m, 1H), 3.37 (dd, 1H, J=18.4 and
4.4Hz), 3.53–3.60 (m, 1H), 3.83 (dd, 1H, J=16.8 and
4.8Hz), 7.22 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz),
7.35 (d, 2H, J=8.0Hz), 7.76 (d, 2H, J=8.0Hz), 8.02 (d,
1H, J=8.0 Hz), 8.25 (d, 1H, J=8.0 Hz); 13C-NMR
(DMSO-d6): 21.69, 22.96, 25.02, 26.98, 30.58, 36.75,
50.08, 114.21, 118.21, 123.02, 124.72, 125.26, 127.06
(2C), 127.48, 131.07 (2C), 135.30, 136.26, 143.46,
146.30, 163.82; HRMS (ESI+): Calcd for C22H22N2SO2
([M+H]+) 378.4562. Found: 378.4551.
([M+ H]+) 224.1168. Found: 224.1161.
2-(4-Oxo-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl)aceto
nitrile (12). A solution of nitrile 11 (2.0g, 8.9mmoles) in
chloroform (25mL) was cooled at 0°C. Then sodium
hydroxide (5mL, 40%), tetrabutylammonium hydrogen
sulfate (50mg), and p-toluene sulfonyl chloride
(10.5mmoles) were added. The reaction mixture was
stirred for 2h and then washed with hydrochloric acid
(50mL, 10%), and organic layer was dried with anhydrous
magnesium sulfate. The solvent was evaporated under
reduced pressure, and the resulting residue was
chromatographed using silica gel and ethyl
acetate/hexane (1:1). After the evaporation of solvents,
the crude product was recrystallized from methanol to
afford N-protected cyano tetrahydrocarbazolone 12
(2.90 g, 86%); mp: 125°C; IR (KBr, νmax, cmꢀ1): 2931
2,3,3a,4,5,6-Hexahydropyrrolo[3,2-c]carbazole (13a).
Yield:
120 mg, 51%; mp: 125°C; IR (KBr, νmax, cmꢀ1): 3225
1
(NH), 2925 (CH), 1609 (C¼N); H NMR (DMSO-d6): δ
1.27–1.39 (m, 1H), 1.52–1.63 (m, 1H), 2.09–2.16 (m, 1H),
2.28–2.31 (m, 1H), 2.77–3.01 (m, 3H), 2.54–2.62 (m, 1H),
3.94 (dd, 1H, J= 14.4 and 8.8Hz), 7.01–7.10 (m, 2H), 7.32
(d, 1H, J= 7.6 Hz), 7.85 (d, 1H, J= 7.6 Hz), 11.45 (s, 1H);
13C-NMR (DMSO-d6): 23.57, 29.77, 30.28, 47.09, 59.53,
107.51, 111.67, 120.55, 120.63, 121.98, 124.87, 136.73,
1
(CH), 2243 (CN), 1675 (C¼O); H NMR (DMSO-d6):
δ 2.04–2.15 (m, 1H) , 2.38 (s, 3H), 2.53–2.62 (m,
2H), 2.79–2.87 (m, 1H), 2.99 (dd, 1H, J = 15.2 and
4.4 Hz), 3.18–3.27 (m, 1H), 3.66 (dd, 1H, J = 15.2 and
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet