PAPER
A Convenient Synthesis of Benzopyrroloquinolines
905
Anal. Calcd for C14H15Cl2NO2 (300.19): C, 56.02; H, 5.04; N, 4.67.
Found: C, 56.20; H, 5.10; N, 4.65.
13C NMR (50 MHz, CDCl3): d = 20.1 (2 q), 22.7 (q), 103.7 (d),
118.1 (s), 124.6 (2 d), 127.4 (d), 127.6 (d), 128.2 (d), 128.9 (2 d),
129.8 (s), 130.6 (s), 131.7 (s), 135.3 (s), 136.5 (d), 142.1 (s), 143.5
(s), 143.7 (s), 144.0 (s), 158.0(s), 182.6 (s), 182.9 (s).
HRMS: m/z calcd for C24H19N2O2: 367.14464 (MH+); found
367.14466.
2,3-Dihydro-6,9-dimethoxy-4-methyl-1-phenyl-1H-pyrrolo[3,2-
c]quinoline (7b)
A solution of 6 (300 mg, 1.0 mmol) and aniline (190 mg, 2.0 mmol)
in EtOH (30 mL) was refluxed for 2 h, and the solvent was removed
in vacuo. The residue was taken up in aq NaHCO3, and the crude
product was extracted with CHCl3. The organic solution was
washed with H2O, dried, and evaporated. Recrystallization from
EtOH gave 7b (225 mg, 70%); mp 188–190 °C.
4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyrrolo[3,2-c]quinoline-
6,11-dione (11) and 4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyr-
rolo[3,2-c]quinoline-6,11-dione (12)
To a solution of quinone 9 obtained from pyrroloquinoline 8 (70
mg, 0.20 mmol) as above, was added penta-1,3-diene (25 mL, 0.25
mmol) and the mixture was heated at 120 °C in a sealed tube for 18
h. After cooling to r.t., the cycloadduct was aromatized by stirring
24 h in the presence of DBU (100 mL). Column chromatography of
the residue, obtained after evaporation of the solvent, on silica gel
(CH2Cl2) gave the aromatized adducts 11 and 12 (50 mg, 64%).
IR (KBr): 1262, 1065, 1090 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.64 (s, 3 H, OCH3), 3.06 (s, 3 H,
CH3), 3.20 (t, J = 9.0 Hz, 2 H, NCH2CH2), 4.00 (s, 3 H, OCH3), 4.23
(t, J = 9.0 Hz, 2 H, NCH2CH2), 6.41 (d, J = 8.7 Hz, 1 H, 7-H or 8-
H), 6.80 (d, J = 8.7 Hz, 1 H, 8-H or 7-H), 6.95 (m, 3 H), 7.20 (m, 2
H).
13C NMR (50 MHz, CDCl3): d = 23.1 (q), 27.0 (t), 54.4 (q), 56.0 (q),
57.7 (t), 102.6 (d), 106.1 (d), 111.4 (s), 120.0 (2 d), 123.0 (d), 123.6
(s), 128.6 (2 d), 142.0 (s), 147.9 (s), 149.2 (s), 150.5 (s), 150.8 (s),
154.4 (s).
HRMS: m/z calcd for C23H17N2O2: 353.12899 (MH+); found:
353.12907.
The mixture of aromatized adducts 11 and 12 was purified by two
consecutive flash chromatography on silica gel (CH2Cl2) to afford
11 and 12.
Anal. Calcd for C20H20N2O2 (320.40): C, 74.98; H, 6.29; N, 8.74.
Found: C, 75.10; H, 6.32; N, 9.04.
11
Yield: 9.0 mg (11%); mp 220–222 °C.
IR (KBr): 1675 cm–1 (C=O).
6,9-Dimethoxy-4-methyl-1-phenyl-1H-pyrrolo[3,2-c]quinoline
(8)
A mixture of 7b (150 mg, 0.47 mmol), 10% Pd/C (30 mg) and mes-
itylene (25 mL) was heated at 200 °C in an autoclave for 24 h. After
removal of the catalyst on Celite, the solvent was evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy using EtOAc–CH2Cl2 (1:1) as eluent to afford pyrroloquino-
line 8 (85 mg, 57%); mp 155–157 °C.
1H NMR (200 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 3.00 (s, 3 H,
CH3), 6.93 (d, J = 3.3 Hz, 1 H, 3-H), 7.32 (m, 2 H, ArH), 7.52 (m,
5 H, ArH), 7.54 (d, J = 3.3 Hz, 1 H, 2-H), 8.21 (d, J = 7.3 Hz,1 H,
7-H).
13C NMR (50 MHz, CDCl3): d = 21.6 (q), 23.1 (q), 103.9 (d), 120.6
(s), 125.0 (2 d), 126.3 (d), 128.1 (d), 129.6 (2 d), 130.0 (s), 132.8 (s),
132.9 (d), 134.5 (s), 135.4 (s), 136.1 (d), 137.6 (d), 139.9 (s), 141.8
(s), 143.0 (s), 158.2 (s), 183.5 (s), 185.8 (s).
IR (KBr): 1615, 1510, 1493, 1260 cm–1.
1H NMR (200 MHz, CDCl3): d = 3.00 (s, 3 H, OCH3), 3.01 (s, 3 H,
CH3), 4.06 (s, 3 H, OCH3), 6.58 (d, J = 8.6 Hz, 1 H, 7-H or 8-H),
6.88 (d, J = 8.6 Hz, 1 H, 8-H or 7-H), 6.89 (d, J = 3.3 Hz, 1 H, 6-H
or 7-H), 7.28 (m, 2 H, ArH), 7.40 (m, 3 H, ArH).
12
Yield: 21 mg (26%); mp 228–230 °C.
13C NMR (50 MHz, CDCl3): d = 23.1 (q), 54.0 (q), 56.2 (q), 103.2
(d), 103.5 (d), 105.0 (d), 110.6 (s), 123.9 (s), 124.4 (2 d), 126.5 (d),
128.7 (2 d), 131.7 (d), 134.2 (s), 137.0 (s), 144.9 (s), 147.0 (s), 149.5
(s), 153.9 (s).
IR (KBr): 1670 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 2.87 (s, 3 H, CH3), 3.00 (s, 3 H,
CH3), 6.91 (d, J = 3.3 Hz, 1 H, 3-H), 7.24 (m, 2 H, ArH), 7.48 (m,
5 H, ArH), 7.51 (d, J = 3.3 Hz, 1 H, 2-H), 7.75 (m, 1 H, 7-H).
Anal. Calcd for C20H18N2O2 (318.38): C, 75.45; H, 5.70; N, 8.80.
Found: C, 75.15; H, 5.95; N, 8.60.
13C NMR (50 MHz, CDCl3): d = 23.2 (q), 23.8 (q), 104.2 (d), 117.5
(s), 125.1 (2 d), 125.4 (d), 128.1 (d), 129.3 (2 d), 129.8 (s), 131.0 (s),
133.2 (d), 135.3 (s), 135.8 (s), 136.5 (d), 137.9 (d), 142.2 (s), 142.3
(s), 144.9 (s), 158.7 (s), 183.5 (s), 184.6 (s).
4,8,9-Trimethyl-1-phenyl-1H-benzo[g]pyrrolo[3,2-c]quinoline-
6,11-dione (10)
To a solution of pyrroloquinoline 8 (70 mg, 0.22 mmol) in MeCN
(5 mL), were added AgO (150 mg, 1.2 mmol) and 6 N HNO3 (0.4
mL). The suspension was stirred for 5 min at r.t., and H2O (10 mL)
was added. The mixture was extracted with CHCl3 (2 × 15 mL), the
combined organic extracts were dried (MgSO4) and filtered. To the
solution was added 2,3-dimethylbuta-1,3-diene (25 mL, 0.22 mmol)
and the mixture was heated at 120 °C in a sealed tube for 18 h. After
cooling to r.t., the cycloadduct was aromatized by stirring 24 h in
the presence of DBU (100 mL). The residue obtained after evapora-
tion of the solvent was purified by flash column chromatography on
silica gel (CH2Cl2) to give compound 10 (65 mg, 81%); mp 233–
235 °C.
Acknowledgment
We are grateful to FONDECYT (Research Grants 2010084 and
1020874) for financial support.
References
(1) Fendrich, G.; Zimmermann, W.; Gruner, J.; Auden, J. A. L.
Eur. Pat. Appl. EP 304400, 1989; Chem. Abstr. 1990, 112,
75295.
(2) (a) Gore, M. P.; Gould, S. J.; Weller, D. D. J. Org. Chem.
1991, 56, 2289. (b) Gore, M. P.; Gould, S. J.; Weller, D. D.
J. Org. Chem. 1992, 57, 2774. (c) Mohri, S.; Stefinovic, M.;
Snieckus, V. J. Org. Chem. 1997, 62, 7072.
(3) (a) Tapia, R. A.; Salas, C.; Morello, A.; Maya, J. D.; Toro-
Labbé, A. Bioorg. Med. Chem. 2004, 12, 2451. (b) Tapia,
R. A.; Prieto, Y.; Pautet, F.; Walchshofer, N.; Fillion, H.;
IR (KBr): 1670 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): d = 2.34 (s, 3 H, CH3), 2.40 (s, 3 H,
CH3), 3.02 (s, 3 H, CH3), 6.92 (d, J = 3.3 Hz, 1 H), 7.28 (m, 2 H,
ArH), 7.50 (m, 3 H, ArH), 7.52 (d, J = 3.3 Hz, 1 H), 7.63 (s, 1 H,
ArH), 8.08 (m, 1 H, ArH).
Synthesis 2005, No. 6, 903–906 © Thieme Stuttgart · New York