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Y.-S. Kim et al. / Bioorg. Med. Chem. 11 (2003) 1709–1714
1.35 g (79%) of red-brown powder. Mp: 168–171 ꢁC; IR
(KBr, cmꢀ1): 1702 (C¼O), 3297 (s, NH); 1H NMR
(CDCl3, d): 8.1 (m, 2H, C5 and C8), 7.7 (m, 2H, C6 and
C7), 7.6 (br, s, 1H, ꢀNH), 7.0 (m, 2H, phenyl), 6.8 (m,
2H, phenyl), 4.6 (m, 1H, ꢀCH(CH3)2), 1.4 (s, 6H,
ꢀOCH(CH3)2).
using 1.71 g (0.5 mmol) of 4c, and the concentrated
residue was purified by column chromatography
(n-hexane/ethyl acetate, 1:5) to give 0.34 g (22%) of
yellow-brown powder. Mp: 242–244 ꢁC; IR (KBr,
1
cmꢀ1): 1670 (C¼O); H NMR (CDCl3, d): 8.5 (m, 2H,
C7 and C10), 8.3 (d, 1H, ꢀCH, C1), 7.9 (m, 2H, C8 and
C9), 7.7 (s, 1H, ꢀCH, C4), 7.6 (d, 1H, ꢀCH, C2), 4.8
(m, 1H, ꢀOCH(CH3)2), 1.5 (d, 6H, ꢀOCH(CH3)2).
Anal. calcd for C19H14N2O3: C, 71.69; H, 4.43; N, 8.80.
Found: C, 71.19; H, 4.69; N, 8.97.
2-(3,4-Methylenedioxyphenylamino)-3-chloro-1,4-naph-
thoquinone (4d). The general procedure was followed
for 6 h using 0.69 g (0.5 mmol) of 3,4-methylenedioxy-
aniline, and the filtered precipitate was crystallized from
ethanol to give 1.25 g (76%) of purple powder. Mp:
238–240 ꢁC; IR (KBr, cmꢀ1): 1715 (C¼O), 3304 (s, NH);
1H NMR (CDCl3, d): 8.1 (m, 2H, C5 and C8), 7.7 (m,
2H, C6 and C7), 7.5 (br, s, 1H, ꢀNH), 6.8 (d, 1H,
phenyl), 6.6 (m, 2H, phenyl), 6.0 (s, 2H, ꢀCH2).
6,11-Dihydro-2,3-methylenedioxy-benzo[2,3-b]phenazine-
6,11-dione (5d). The general procedure was followed for
20 h using 1.64 g (0.5 mmol) of 4d, and the concentrated
residue was purified by column chromatography (n-hex-
ane/ethyl acetate, 1:4) to give 0.28 g (19%) of yellow-
brown powder. Mp: 306–309 ꢁC; IR (KBr, cmꢀ1): 1657
1
2-(3,4-Dimethylphenylamino)-3-chloro-1,4-naphthoqui-
none (4e). The general procedure was followed for 5 h
using 0.61 g (0.5 mmol) of 3,4-dimethylaniline, and the
filtered precipitate was crystallized from ethanol to give
1.33 g (85%) of red-brown powder. Mp: 177–180 ꢁC; IR
(KBr, cmꢀ1): 1724 (C¼O), 3335 (s, NH); 1H NMR
(CDCl3, d): 8.1 (m, 2H, C5 and C8), 7.7 (m, 2H, C6 and
C7), 7.6 (br, s, 1H, ꢀNH), 7.1 (d, 1H, ꢀCH, C5), 6.9 (s,
1H, phenyl), 6.8 (d, 1H, phenyl), 2.3 (s, 6H, 2ꢂCH3).
(C¼O); H NMR (acetone-d6, d): 8.4 (m, 2H, C8 and
C11), 8.0 (m, 2H, C9 and C10), 7.6 (s, 2H, C1 and C5), 6.5
(s, 2H, ꢀCH2, C3). Anal. calcd for C17H8N2O4: C, 67.11;
H, 2.65; N, 9.21. Found: C, 66.77; H, 2.77; N, 9.29.
6,11-Dihydro-2,3-dimethyl-benzo[2,3-b]phenazine-6,11-
dione (5e). The general procedure was followed for 18 h
using 1.44 g (0.5 mmol) of 4e, and the concentrated
residue was purified by column chromatography
(n-hexane/ethyl acetate, 1:5) to give 0.56 g (39%) of yel-
low-brown powder. Mp: 298–299 ꢁC; IR (KBr, cmꢀ1):
General procedure for the preparation of 6,11-dihydro-
benzo[2,3-b]phenazine-6,11-diones (5a–e). A mixture of
0.5 mmol of 4a–e, 50 mL of DMF and 0.65 g (0.01 mol)
of sodium azide, suspended in a little amount of water,
was heated on the steam bath overnight. The reaction
mixture was chilled, the filtered precipitate was extrac-
ted with methylene chloride and concentrated, and then
the residue was purified by column chromatography.
1
1670 (C¼O); H NMR (CDCl3, d): 8.5 (m, 2H, C7 and
C10), 8.2 (d, 1H, ꢀCH, C4), 7.9 (m, 2H, C8 and C9), 7.8
(d, 1H, ꢀCH, C1), 3.0 (s, 3H, ꢀCH3, C3), 2.6 (s, 3H,
ꢀCH3, C4). Anal. calcd for C18H12N2O2: C, 74.99; H,
4.20; N, 9.72. Found: C, 74.62; H, 4.11; N, 9.62.
General procedure for the preparation of 6-arylamino-7-
chloro-5,8-quinolinediones (8a–e). Arylamine (0.05
mmol) was added to a mixture of 6,7-dichloro-5,8-
6,11-Dihydro-2-methoxy-benzo[2,3-b]phenazine-6,11-dione
(5a). The general procedure was followed for 20 h using
1.57 g (0.5 mmol) of 4a, and the concentrated residue
was purified by column chromatography (n-hexane/
ethyl acetate, 1:4) to gꢁive 0.59 g (41%) of yellow-brown
powder. Mp: 330–331 C; IR (KBr, cmꢀ1): 1705 (C¼O);
1H NMR (CDCl3, d): 8.5 (m, 2H, C7 and C10), 8.3 (d,
1H, ꢀCH, C4), 7.9 (m, 2H, C8 and C9), 7.7 (s, 1H,
ꢀCH, C1), 7.6 (d, 1H, ꢀCH, C3), 4.0 (s, 3H, ꢀOCH3).
Anal. calcd for C17H10N2O3: C, 70.34; H, 3.47; N, 9.65.
Found: C, 70.30; H, 3.64; N, 9.63.
.
naphthoquinone (1.14 g, 0.5 mmol) and CeCl3 7H2O
(cerium chloride hepatahydrate) (0.5 g) in ethanol (100
mL) and heated under reflux. The reaction mixture was
cooled and then filtered. The filtered precipitation was
crystallized from 95% ethanol.
6-(3-Methoxyphenylamino)-7-chloro-5,8-quinolinedione
(8a). The general procedure was followed for 8 h using
0.56 mL (0.5 mmol) of 3-methoxyaniline, and the filtered
precipitate was crystallized from ethanol to give 1.29 g
(82%) of dark purple powder. Mp: 152–154 ꢁC; IR (KBr,
cmꢀ1): 1679 (C¼O), 3284 (s, NH); 1H NMR (acetone-d6,
d): 9.0 (d, 1H, ꢀCH, C2), 8.5 (br. s, 1H, ꢀNH), 8.4 (d,
1H, ꢀCH, C4), 7.8 (dd, 1H, ꢀCH, C3), 7.2 (t, 1H,
phenyl), 6.7 (m, 3H, phenyl), 3.8 (s, 3H, ꢀOCH3).
6,11-Dihydro-3-ethoxy-benzo[2,3-b]phenazine-6,11-dione
(5b). The general procedure was followed for 20 h
using 1.64 g (0.5 mmol) of 4b, and the concentrated
residue was purified by column chromatography (n-
hexane/ethyl acetate, 1:3) to give 0.57 g (40%) of yel-
low-brown powder. Mp: 254–255 ꢁC; IR (KBr, cmꢀ1):
6-(4-Ethoxyphenylamino)-7-chloro-5,8-quinolinedione (8b).
The general procedure was followed for 4 h using 0.65
mL (0.5 mmol) of 4-ethoxyaniline, and the filtered pre-
cipitate was crystallized from ethanol to give 1.50 g
(91%) of dark brown powder. Mp: 197–199 ꢁC; IR
(KBr, cmꢀ1): 1713 (C¼O), 3370 (s, NH); 1H NMR
(acetone-d6, d): 9.0 (d, 1H, ꢀCH, C2), 8.5 (br, s, 1H,
ꢀNH), 8.4 (d, 1H, ꢀCH, C4), 7.8 (dd, 1H, ꢀCH, C3), 7.2
(m, 2H, phenyl), 6.9 (m, 2H, phenyl), 4.1 (q, 2H,
ꢀOCH2CH3), 1.4 (t, 3H, ꢀOCH2CH3).
1
1701 (C¼O); H NMR (CDCl3, d): 8.5 (m, 2H, C7 and
C10), 8.3 (d, 1H, ꢀCH, C1), 7.9 (m, 2H, C8 and C9), 7.7
(s, 1H, ꢀCH, C4), 7.6 (d, 1H, ꢀCH, C2), 4.3 (q, 2H,
ꢀOCH2CH3), 1.6 (t, 3H, ꢀOCH2CH3). Anal. calcd for
C18H12N2O3: C, 71.05; H, 3.97; N, 9.21. Found: C,
70.65; H, 4.05; N, 9.22.
6,11-Dihydro-3-isopropoxy-benzo[2,3-b]phenazine-6,11-
dione (5c). The general procedure was followed for 22 h