L. de Carvalho Tavares et al. / European Journal of Medicinal Chemistry 46 (2011) 4448e4456
4453
143.91, 136.48, 134.37, 134.34, 132.96, 131.16, 131.06, 130.31, 130.08,
128.30, 127.25, 122.62, 121.91, 115.92, 115.70; Anal. Calcd. for C18
H12FNO: C, 77.97; H, 4.36; N, 5.05. Found: C, 77.53; H, 3.68; N, 5.11.
135.53, 135.16, 130.77, 129.53, 129.43 (two C, Ar), 128.69 (two C, Ar),
128.19, 125.98, 124.51, 121.85, 120.67, 21.67; Anal. Calcd. for C19
H15NO2: C, 78.87; H, 5.23; N, 4.84. Found: C, 78.38; H, 5.43; N, 4.88.
4.1.1.6. (2E)-1-(4-Bromophenyl)-3-(6-quinolinyl)-2-propen-1-one
4.1.2.3. (2E)-1-(4-Methoxyphenyl)-3-(1-oxide-6-quinolinyl)-2-
propen-1-one (4c). Chromatography: 45% EtOAc-hexane; yield
73%; pale yellow solid; m.p. 187e189 ꢁC; IR (KBr, cmꢀ1) 1655 (C]
(3f). Yield 61%; yellow solid; m.p. 199e200 ꢁC; IR (KBr, cmꢀ1) 1657
(C]O), 1573 (C]C); 1H NMR (400 MHz, CDCl3, ppm):
d
8.9 (dd,
J ¼ 4.2, 1.5 Hz, 1H, Ar-Qn), 8.2 (d, J ¼ 7.8 Hz, 1H, Ar-Qn), 8.1 (d,
J ¼ 8.8 Hz, 1H, Ar-Qn), 8.0 (m, 3H, (2 Ar-Qn, 1H )), 7.9 (d, J ¼ 8.6 Hz,
), 7.5 (dd,
O), 1568 (C]C), 1260 (N-O); 1H NMR (400 MHz, CDCl3, ppm):
d
8.8
(d, J ¼ 9.0 Hz,1H, Ar-Qn), 8.5 (d, J ¼ 5.9 Hz,1H, Ar-Qn), 8.0 (m, 4 H, (2
Ar-Qn, 2 Ar)), 7.9 (d, J ¼ 15.7 Hz, 1H, H ), 7.8 (d, J ¼ 8.3 Hz, 1H, Ar-
b
2H, Ar), 7.7 (d, J ¼ 8.3 Hz, 2 H, Ar), 7.6 (d, J ¼ 15.7 Hz,1H, H
a
b
J ¼ 8.3, 4.4 Hz, 1H, Ar-Qn); 13C NMR (100 MHz, CDCl3, ppm):
Qn), 7.7 (d, J ¼ 15.7 Hz, 1H, H ), 7.3 (dd, J ¼ 8.3, 6.1 Hz, 1H, Ar-Qn),
a
d
189.01,151.52,149.24,144.28,136.76,136.49,132.91,131.99 (two C,
7.0 (d, J ¼ 8.8 Hz, 2 H, Ar), 3.9 (s, 3 H, OCH3); 13C NMR (100 MHz,
Ar), 130.38, 130.19, 130.02 (two C, Ar), 128.31, 128.11, 127.25, 122.51,
121.95; Anal. Calcd. for C18 H12BrNO: C, 63.92; H, 3.58; N, 4.14.
Found: C, 63.29; H, 3.66; N, 4.09.
CDCl3, ppm): d 187.90, 163.72, 141.96, 141.45, 136.22, 135.62, 130.90
(two C, Ar), 130.77, 130.64, 129.42, 128.19, 126.00, 124.38, 121.83,
120.65, 113.96 (two C, Ar), 55.49; Anal. Calcd. for C19 H15NO3: C,
74.74; H, 4.95; N, 4.59. Found: C, 74.66; H, 5.01; N, 4.62.
4.1.1.7. (2E)-1-(4-Chlorophenyl)-3-(6-quinolinyl)-2-propen-1-one
(3g). Yield 51%; yellow solid; m.p. 196e198 ꢁC; IR (KBr, cmꢀ1) 1658
4.1.2.4. (2E)-1-(4-Nitrophenyl)-3-(1-oxide-6-quinolinyl)-2-propen-
1-one (4d). Chromatography: 5% EtOH-CH2Cl2; yield 70%; yellow
solid; m.p. 256e257 ꢁC; IR (KBr, cmꢀ1) 1664 (C]O), 1571 (C]C),
(C]O), 1570 (C]C); 1H NMR (400 MHz, CDCl3, ppm):
d
9.0 (dd,
J ¼ 4.3, 1.6 Hz, 1H, Ar-Qn), 8.2 (d, J ¼ 7.3 Hz, 1H, Ar-Qn), 8.1 (d,
J ¼ 8.8 Hz, 1H, Ar-Qn), 8.0 (m, 5H, (2 Ar-Qn, 2 Ar, 1H )), 7.6 (d,
J ¼ 15.7 Hz, 1H, H ), 7.51 (d, J ¼ 8.6 Hz, 2H, Ar), 7.5 (dd, J ¼ 8.3,
4.2 Hz, 1H, Ar-Qn); 13C NMR (100 MHz, CDCl3, ppm):
188.73,
b
211 (NeO); 1H NMR (400 MHz, CDCl3, ppm):
d
8.8 (d, J ¼ 9.5 Hz, 1H,
Ar-Qn), 8.6 (d, J ¼ 6.1 Hz,1H, Ar-Qn), 8.4 (d, J ¼ 8.8 Hz, 2H, Ar), 8.2 (d,
J ¼ 8.6 Hz, 2H, Ar), 8.0 (m, 2H, Ar-Qn), 8.0 (d, J ¼ 15.7 Hz,1H, H ), 7.8
a
d
b
151.48, 149.19, 144.16, 139.37, 136.45, 136.28, 132.86, 130.32, 130.14,
129.87 (two C, Ar), 128.97 (two C, Ar), 128.26, 127.21, 122.46, 121.90;
Anal. Calcd. for C18 H12ClNO: C, 73.60; H, 4.12; N, 4.77. Found: C,
73.10; H, 4.13; N, 4.84.
(d, J ¼ 8.3 Hz, 1H, Ar-Qn), 7.6 (d, J ¼ 15.7 Hz, 1H, H ), 7.4 (dd, J ¼ 7.8,
a
6.4 Hz, 1H, Ar-Qn); 13C NMR (100 MHz, CDCl3 þ CD3OD, ppm):
d
188.39, 150.33, 143.10, 142.09, 139.50, 136.01, 135.03, 131.08,
130.72,129.97 (two C),129.55 (two C, Ar),124.83,123.92 (two C, Ar),
122.20, 119.71. Anal. Calcd. for C18 H12N2O4: C, 67,50; H, 3.78; N,
8.75. Found: C, 67.88; H, 3.52; N, 8.55.
4.1.2. General procedure for synthesis of 6-quinolinyl N-oxide
chalcones (4aeg)
To a solution of 6-quinolinyl chalcones 3aeg (2 mmol) in
dichloromethane (CH2Cl2) (8 mL) at 0 ꢁC was added a solution of
77% m-chloroperoxybenzoic acid (m-CPBA) (0. 85 g, 3.69 mmol) in
4 mL of CH2Cl2 dropwise over a period of 10 min. After that, the
reaction was stirred at room temperature for 13 h. To a mixture was
added 1 mL of 10% aqueous sodium sulfite solution and was stirred
for 1e2 min. The reaction was filtered and solid residue was
washed with several small portions of CH2Cl2. The combined
organic layers were washed with 10% Na2CO3 solution (3 ꢄ 15 mL).
The solution was dried over anhydrous MgSO4. All the compounds
were purified by column chromatography on silica gel to give the
pure analytically 6-quinolinyl N-oxide chalcones 4aeg.
4.1.2.5. (2E)-1-(4-Fluorophenyl)-3-(1-oxide-6-quinolinyl)-2-propen-
1-one (4e). Chromatography: 30% EtOAc-hexane; yield 73%; pale
yellow solid; m.p. 216e218 ꢁC; IR (KBr, cmꢀ1) 1668 (C]O), 1566
(C]C), 1222 (NeO); 1H NMR (400 MHz, CDCl3, ppm):
d
8.8 (d,
J ¼ 8.8 Hz, 1H, Ar-Qn), 8.6 (d, J ¼ 2.9 Hz, 1H, Ar-Qn), 8.1 (m, 4H, (2
Ar-Qn, 2 Ar)), 8.0 (d, J ¼ 15.7 Hz, 1H, H ), 7.8 (d, J ¼ 8.8 Hz, 1H, Ar-
Qn), 7.7 (d, J ¼ 15.7 Hz, 1H, H ), 7.4 (m, 1H, Ar-Qn), 7.2 (m, 2H, Ar);
13C NMR (100 MHz, CDCl3, ppm):
188.10, 167.17, 164.62, 142.44,
b
a
d
141.93, 136.87, 135.54, 134.14, 134.11, 131.29, 131.19, 130.81, 129.70,
128.58, 127.16, 124.29, 121.93, 120.78, 116.08, 115.87. Anal. Calcd.
for C18 H12 FNO2: C, 73.71; H, 4.12; N, 4.78. Found: C,73.58; H, 4.23;
N, 4.87.
4.1.2.1. (2E)-3-(1-oxide-6-quinolinyl)-1-phenyl-2-propen-1-one
(4a). Chromatography: 30% EtOAc-hexane; yield 65%; pale yellow
solid; m.p. 148e150 ꢁC; IR (KBr, cmꢀ1) 1674 (C]O), 1571 (C]C),
4.1.2.6. (2E)-1-(4-Bromophenyl)-3-(1-oxide-6-quinolinyl)-2-propen-
1-one (4f). Chromatography: 30% EtOAc-hexane; yield 67%; pale
yellow solid; m.p. 186e188 ꢁC; IR (KBr, cmꢀ1) 1663 (C]O), 1567
1204 (N-O); 1H NMR (400 MHz, CDCl3, ppm):
d
8.9 (d, J ¼ 5.4 Hz,1H,
Ar-Qn), 8.8 (d, J ¼ 9.0 Hz, 1H, Ar-Qn), 8.2 (d, J ¼ 9.3 Hz, 1H, Ar-Qn),
8.1 (m, 4 H, (2 Ar-Qn, 2 Ar)), 7.9 (d, J ¼ 15.7 Hz,1H, H ), 7.7 (d,
J ¼ 15.7 Hz, 1H, H ), 7.6 (m, 1H, Ar), 7.5 (m, 2 H, Ar), 7.4 (m, 1H, Ar-
Qn); 13C NMR (100 MHz, CDCl3, ppm):
189.83, 142.32, 137.80,
(C]C), 1208 (N-O); 1H NMR (400 MHz, CDCl3, ppm):
d
8.8 (d,
J ¼ 9.0 Hz, 1H, Ar-Qn), 8.6 (d, J ¼ 6.1 Hz, 1H, Ar-Qn), 8.1 (m, 1H, Ar-
b
Qn), 8.0 (m, 3H, (1H
b
, 2 Ar)), 7.8 (d, J ¼ 8.6 Hz,1H, Ar-Qn), 7.7 (m, 3H,
a
(1H
a
, 2 Ar)), 7.4 (dd, J ¼ 8.3, 6.1 Hz, 1H, Ar-Qn); 13C NMR (100 MHz,
d
CDCl3, ppm): d 188.68, 142.91, 142.19, 136.46, 136.39, 135.24, 132.09
136.49, 135.56, 133.21, 129.63, 128.79, 128.70 (two C, Ar), 128.59
(two C, Ar),128.37,128.07,126.37,124.65,121.92,120.81. Anal. Calcd.
for C18 H13NO2: C, 78.53; H, 4.76; N, 5.09. Found: C, 78.55; H, 4.74; N,
5.13.
(two C, Ar), 130.80, 130.06 (two C, Ar), 129.85, 128.41, 128.11, 125.91,
123.89, 122.00, 120.87; Anal. Calcd. for C18 H12BrNO2: C, 61.04; H,
3.41; N, 3.95. Found: C, 61.13; H, 3.36; N, 3.93.
4.1.2.7. (2E)-1-(4-Chlorophenyl)-3-(1-oxide-6-quinolinyl)-2-propen-
1-one (4g). Chromatography: 30% EtOAc-hexane; yield 77%; pale
yellow solid; m.p. 180e182 ꢁC; IR (KBr, cmꢀ1) 1668 (C]O), 1566
4.1.2.2. (2E)-1-(4-Methylphenyl)-3-(1-oxide-6-quinolinyl)-2-
propen-1-one (4b). Chromatography: 30% EtOAc-hexane; yield
78%; pale yellow solid; m.p.176e177 ꢁC; IR (KBr, cmꢀ1) 1661 (C]O),
(C]C), 1222 (NeO); 1H NMR (400 MHz, CDCl3, ppm):
d
8.8 (d,
J ¼ 8.8 Hz,1H, Ar-Qn); 8.6 (d, J ¼ 5.9 Hz,1H, Ar-Qn), 8.0 (m, 4H (2 Ar-
Qn, 2 Ar)), 7.9 (d, J ¼ 15.7 Hz, 1H, H ), 7.8 (d, J ¼ 8.6 Hz, 1H, Ar-Qn),
7.7 (d, J ¼ 15.7 Hz, 1H, H ), 7.5 (d, J ¼ 8,55, 2H, Ar), 7.4 (dd, J ¼ 8.6,
6.1 Hz, 1H, Ar-Qn); 13C NMR (100 MHz, CDCl3, ppm):
188.36,
1567 (C]C), 1294 (N-O); 1H NMR (400 MHz, CDCl3, ppm):
d 8.8 (d,
J ¼ 9.0 Hz, 1H, Ar-Qn), 8.5 (d, J ¼ 6.1 Hz, 1H, Ar-Qn), 8.1 (dd, J ¼ 9.0,
b
1.7 Hz,1H, Ar-Qn), 8.0 (s, 1H, Ar-Qn), 8.0 (d, J ¼ 8.1 Hz, 2H, Ar), 7.9 (d,
a
J ¼ 15.7 Hz, 1H, H
1H, H
(100 MHz, CDCl3, ppm):
b
), 7.8 (d, J ¼ 8.3 Hz, 1H, Ar-Qn), 7.7 (d, J ¼ 15.7 Hz,
d
a
), 7.3 (m, 3 H, (1 Ar-Qn, 2 Ar)), 2.5 (s, 3H, CH3); 13C NMR
189.22, 144.14, 142.00, 141.87, 136.23,
142.75, 142.09, 139.62, 136.30, 135.97, 135.16, 130.72, 129.90 (two C,
Ar), 129.77, 129.02 (two C, Ar), 128.04, 125.84, 123.84, 121.93,
d