Thermal C2-C6 Cyclization of Enyne-Carbodiimides
10C4H8O2 (353.38): C, 74.28; H, 4.40; N, 11.60. Found: C, 74.29;
H, 3.99; N, 11.54.
175 (30), 153 (11); ESI-MS (C24H22N3+) m/z calcd 352.2, found
352.2. Anal. Calcd for C24H21N3‚0.2H2O (351.44): C, 81.19; H,
6.08; N, 11.84. Found: C, 81.37; H, 6.07; N, 11.82.
11-(p-Cyanophenyl)-9-methyl-6H-indolo[2,3-b]quinoline (12c).
Thermolysis of 7c was carried out in toluene at reflux temperature
for 6.5 h. Column chromatography (silica gel, n-hexane:ethyl acetate
) 4:1) yielded 12c as a yellow solid: yield 65%; mp > 323 °C
dec; IR (KBr) ν˜ ) 3122 (br, m), 3027 (br, m), 2922 (w), 2852 (w),
2228 (m, CtN), 1620 (m), 1606 (m), 1588 (m), 1486 (m), 1402
(m), 1384 (m), 1354 (m), 1301 (w), 1250 (w), 1233 (w), 1218 (w),
9-Methyl-2-nitro-11-phenyl-6H-indolo[2,3-b]quinoline (12g).
Heating of 7g for 5 h under reflux in toluene led to complete
conversion of the reactant. Upon cooling, 12g was isolated by
crystallization as a yellow solid: yield 75%; mp > 340 °C dec; IR
(KBr) ν˜ ) 3145 (br, m), 3088 (br, m), 2923 (m), 2856 (m), 1598
(s), 1503 (m), 1406 (w), 1380 (w), 1330 (s, NdO), 1290 (w), 1250
(m), 1229 (m), 1216 (m), 1093 (m), 841 (w), 830 (w), 704 (m)
cm-1; 1H NMR (100 MHz, DMSO-d6) δ ) 2.21 (3H, s), 6.74 (1H,
s), 7.34 (1H, d, J ) 8.2 Hz), 7.43 (1H, d, J ) 8.2 Hz), 7.62-7.65
(2H, m), 7.77-7.79 (3H, m), 8.16 (1H, d, J ) 9.3 Hz), 8.38 (1H,
dd, J ) 9.3 and 2.5 Hz), 8.63 (1H, d, J ) 2.5 Hz), 12.22 (1H, br
s, NH); 13C NMR (50 MHz, DMSO-d6) δ ) 21.2, 111.3, 117.2,
119.8, 121.4, 121.9, 122.7, 123.0, 128.7, 129.1, 129.2, 129.4, 129.5,
130.1, 134.6, 139.9, 141.9, 143.2, 148.9, 154.5; MS (EI, 70 eV)
m/z (rel intens) ) 353 (100, M+), 323 (18), 307 (23), 292 (43, M+
- NO2 - CH3); HR-MS (C22H15N3O2) m/z calcd for [M]+
353.1164, found 353.1161.
2-Cyano-9-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (12h).
To 25 mL of toluene was added 7h (26.0 mg, 77.9 µmol). After
the reaction mixture was refluxed for 12 h, the product was purified
by column chromatography (silica gel, n-hexane:diethyl ether )
1:1), yielding 25.7 mg of 12h (77.1 µmmol, 98%) as a yellow solid;
mp > 340 °C dec; IR (KBr) ν˜ ) 3302 (br s), 3057 (w), 2919 (w),
2854 (w), 2224 (s, CtN), 1069 (m), 1595 (s), 1577 (m), 1483 (m),
1402 (m), 1378 (m), 1356 (m), 1287 (m), 1257 (m), 1234 (w),
1123 (w), 1033 (w), 822 (m), 805 (m) cm-1; 1H NMR (200 MHz,
CDCl3) δ ) 2.28 (3H, s), 6.85 (1H, s), 7.20-7.26 (1H, m), 7.32
(1H, d, J ) 8.1 Hz), 7.46-7.50 (2H, m), 7.70-7.73 (3H, m), 7.82
(1H, dd, J ) 8.8, 1.8 Hz), 8.11 (1H, d, J ) 1.8 Hz), 8.15 (1H, d,
J ) 8.8 Hz), 10.58 (1H, br s); 13C NMR (100 MHz, CDCl3) δ )
21.4, 106.0, 110.6, 117.7, 119.6, 120.8, 123.4, 123.6, 128.2, 129.2
(2C), 129.3 (2C), 129.9, 130.3, 133.2, 134.9, 138.9, 142.9, 147.7,
154.1; MS (EI, 70 eV) m/z (rel intens) ) 333 (100, M+), 332 (41),
330 (13), 317 (11), 51(21), 39(12). Anal. Calcd for C23H15N3
(333.39): C, 82.86; H, 4.54; N, 12.60. Found: C, 82.24; H, 4.65;
N, 12.42.
1
1023 (w), 843 (w), 783 (m) cm-1; H NMR (200 MHz, DMSO-
d6) δ ) 2.21 (3H, s), 6.65 (1H, s), 7.28 (1H, dd, J ) 8.5, 1.2 Hz),
7.39 (1H, ddd, J ) 8.5, 6.8, 1.2 Hz), 7.40 (1H, d, J ) 8.2 Hz),
7.51 (1H, dd, J ) 8.5, 1.2 Hz), 7.73 (1H, ddd, J ) 8.5, 6.8, 1.2
Hz), 7.79 (2H, d, J ) 8.4 Hz), 8.04 (1H, d, J ) 8.2 Hz), 8.19 (2H,
d, J ) 8.4 Hz), 11.80 (1 H, br s, NH); 13C NMR (50 MHz, DMSO-
d6) δ ) 21.1, 110.9, 111.7, 115.1, 118.9, 119.8, 122.2, 122.3, 123.2,
125.4, 127.4, 128.2, 128.8, 129.5, 130.5, 133.2, 139.4, 139.9, 141.2,
146.2, 152.5. Anal. Calcd for C23H15N3‚1/12C4H8O2 (333.39): C,
82.25; H, 4.63; N, 12.33. Found: C, 82.29; H, 4.41; N, 12.36.
11-(p-Chlorophenyl)-9-methyl-6H-indolo[2,3-b]quinoline (12d).
Thermolysis of 7d was carried out in toluene at reflux temperature
for 6 h. Purification of the product by column chromatography
(silica gel, n-hexane:ethyl acetate ) 7:3) yielded 12d as a yellow
solid: yield 52%; mp 278-280 °C; IR (KBr) ν˜ ) 3135 (m), 3061
(m), 2915 (w), 2852 (w), 1598 (s), 1485 (s), 1379 (m), 1354 (m),
1
1249 (m), 1228 (m), 1089 (s), 839 (s), 816 (m), 757 (s) cm-1; H
NMR (400 MHz, CDCl3) δ ) 2.32 (3H, s), 6.91 (1H, s), 7.24 (1H,
d, J ) 8.3 Hz), 7.38-7.42 (2H, m), 7.49 (2H, d, J ) 8.5 Hz), 7.67
(2H, d, J ) 8.5 Hz), 7.70 (1H, dd, J ) 8.3 and 0.8 Hz), 7.75 (1H,
ddd, J ) 7.5, 6.4, 1.3 Hz), 8.21 (1H, d, J ) 8.1 Hz), 11.41 (1H, br
s, NH); 13C NMR (100 MHz, CDCl3) δ ) 21.5, 110.5, 116.5, 120.9,
123.0, 123.1, 123.5, 126.2, 126.7, 128.9, 129.2 (2C), 130.9 (2C),
134.7, 134.9, 139.5, 141.1, 146.2, 153.3; MS (EI, 70 eV) m/z (rel
intens) ) 342 (100, M+), 341 (41), 305 (20), 153 (30), 75 (39), 63
(34), 52 (43), 50 (44), 39 (84), 28 (47), 27 (93); ESI-MS (C22H16-
ClN2+) m/z calcd 343.1, found 343.1.
11-(p-Methoxyphenyl)-9-methyl-6H-indolo[2,3-b]quinoline (12e).
Thermolysis of 7e was carried out in toluene at 75 °C for 7 h.
Column chromatography (silica gel, n-hexane:ethyl acetate ) 3:1)
afforded 12e as a yellow solid: yield 79%; mp 284-286 °C; IR
(KBr) ν˜ ) 3131 (br, m), 2997 (br, m), 2960 (m), 2930 (m), 2833
(m), 1607 (s), 1507 (m), 1486 (w), 1439 (w), 1381 (w), 1355 (w),
1293 (m), 1249 (s), 1178 (m), 1036 (m), 841 (w), 803 (w), 758
(m) cm-1; 1H NMR (400 MHz, DMSO-d6) δ ) 2.21 (3H, s), 3.92
(3H, s), 6.84 (1H, s), 7.24-7.27 (3H, m), 7.36 (1H, d, J ) 7.8
Hz), 7.37 (1H, dd, covered), 7.47 (2H, d, J ) 7.5 Hz), 7.64-7.61
(2H, m), 8.00 (1H, d, J ) 8.6 Hz), 11.68 (1H, br s, NH); 13C NMR
(100 MHz, DMSO-d6) δ ) 21.2, 55.4, 110.6, 114.5, 115.6, 120.5,
121.7, 122.5, 122.6, 123.2, 125.9, 127.2, 127.8, 128.5, 129.0, 130.6,
139.7, 141.4, 146.4, 152.7, 159.5. Anal. Calcd for C23H18N2O
(338.41): C, 81.63; H, 5.36; N, 8.28. Found: C, 81.41; H, 5.44;
N, 8.39.
9-Methyl-11-[4-(N,N-dimethylamino)phenyl]-6H-indolo[2,3-
b]quinoline (12f). Crude 7f, synthesized from 6f (100 mg, 260
µmol) in 5 mL of dry dichloromethane, was allowed to warm to
room temperature for 30 min. After washing with water, the solvent
was removed under reduced pressure. Column chromatography
(silica gel, n-hexane:diethyl ether 1:4) yielded 41.0 mg of 12f (120
µmol, 45%) as a dark yellow solid: mp 306 °C (DSC); IR (KBr)
ν˜ ) 3019 (s, N-H), 2400 (m, N-H), 1605 (m), 1524 (m), 1482
(w), 1444 (w), 1358 (m), 1216 (s), 1126 (m), 1053 (m), 929 (w),
756 (s), 668 (s) cm-1; 1H NMR (200 MHz, CDCl3) δ ) 2.32 (3H,
s), 3.12 (6H, s), 6.98 (2H, d, J ) 7.8 Hz), 7.16 (1H, s), 7.24 (1H,
m), 7.35-7.45 (4H, m), 7.73 (1H, t, J ) 7.5 Hz), 7.91 (1H, d, J )
8.5, 1.2 Hz), 8.18 (1H, d, J ) 8.5 Hz), 10.81 (1H, br s); 13C NMR
(100 MHz, CDCl3) δ ) 21.5, 42.0, 110.2, 112.4, 116.7, 121.7,
122.5, 123.5, 123.7, 124.4, 126.6, 126.9, 128.6, 128.8, 128.9, 130.4,
139.2, 143.6, 146.5, 150.6, 153.5; MS (EI, 70 eV) m/z (rel intens)
) 351 (100, M+), 350 (20, M+ - H), 335 (12, M+ - H - CH3),
2-Chloro-9-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (12i).
12i was obtained from thermolysis of 7i in refluxing toluene (5 h).
12i was isolated by column chromatography (silica gel, n-hexane:
ethyl acetate ) 7:3) as a yellow solid: yield 54%; mp 256-258
°C; IR (KBr) ν˜ ) 3140 (br, m), 3022 (m), 2917 (m), 2855 (w),
1616 (s), 1484 (m), 1401 (m), 1350 (m), 1290 (w), 1245 (s), 1215
1
(w), 1176 (w), 1081 (w), 817 (m), 703 (s) cm-1; H NMR (400
MHz, CDCl3) δ ) 2.24 (3H, s), 6.73 (1H, s), 7.00 (1H, d, J ) 8.2
Hz), 7.15 (1H, d, J ) 8.2 Hz), 7.38-7.41 (2H, m), 7.48 (1H, dd,
J ) 8.9 and 2.3 Hz), 7.58 (1H, d, J ) 2.3 Hz), 7.65-7.68 (3H, m),
7.97 (1H, J ) 8.9 Hz), 12.55 (1 H, s, NH); 13C NMR (100 MHz,
CDCl3) δ ) 21.3, 110.4, 117.0, 120.4, 123.1, 123.9, 124.9, 127.6,
128.0, 128.8, 128.9, 129.0, 129.1 (2C), 129.4, 135.6, 139.6, 141.4,
144.4, 153.1; MS (EI, 70 eV) m/z (rel intens) ) 342 (100, M+),
341 (36), 305 (21, M+ - Cl), 51 (15); ESI-MS (C22H16ClN2+) m/z
calcd 343.1, found 343.1.
2-Methoxy-9-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (12j).
12j could be obtained from thermolysis of 7j in refluxing toluene
(30 min). 12j was isolated by column chromatography (silica gel,
n-hexane:ethyl acetate ) 1:1) as a yellow solid: yield 76%; mp
249-251 °C; IR (KBr) ν˜ ) 3144 (br, s), 3054 (br, m), 2922 (m),
2832 (w), 1622 (s), 1586 (m), 1516 (m), 1485 (m), 1469 (m), 1450
(m), 1399 (m), 1351 (m), 1296 (m), 1250 (m), 1235 (s), 1225 (s),
1163 (m), 1116 (w), 1036 (s), 883 (w), 819 (s), 795 (m), 732 (s),
1
702 (m) cm-1; H NMR (200 MHz, DMSO-d6) δ ) 2.15 (3H, s),
3.64 (3H, s), 6.66 (1H, m), 6.91 (1H, d, J ) 2.8 Hz), 7.22 (1H, d,
J ) 8.2 Hz), 7.35 (1H d, J ) 8.2 Hz), 7.40 (1H, dd, J ) 9.4, 2.8
Hz), 7.51-7.56 (2H, m), 7.65-7.76 (3H, m), 7.94 (1H, d, J ) 9.4
Hz), 11.56 (1 H, s, NH); 13C NMR (50 MHz, DMSO-d6) δ ) 21.1,
55.1, 104.0, 110.2, 115.5, 120.1, 120.2, 122.4, 123.2, 127.6, 128.6,
J. Org. Chem, Vol. 73, No. 8, 2008 3015