42
S.-Y. Li et al. / European Journal of Medicinal Chemistry 71 (2014) 36e45
4.1.1. General procedures for the preparation of compounds 1e20
Compounds 1e20 were easily prepared as described in the
literature with some modification [34]. In brief, the mixture of aro-
matic aldehyde and aniline were stirred in a small amountof ethanol
at reflux condition for about 2 h then followed by filtration and
recrystallization in EtOAc or MeOH to obtain the pure compounds.
4.1.1.6. (E)-2-((3-Fluorobenzylidene)amino)phenol (6). Yield 72%,
lightyellowsolid,m.p. 77e78ꢅC;IR(KBr)
3065.33,2929.95,2319.34,
1625.97, 1585.56, 1488.55, 1384.77, 1288.43, 1245.13,1173.88, 1152.07,
811.78, 786.77, 752.55 cmꢀ1. 1H NMR (500 MHz, DMSO-d6)
9.04 (s,
n
d
1H, OH), 8.75 (s,1H, CH]N), 7.96 (ddd, J ¼ 10.1, 2.6,1.3 Hz,1H, AreH),
7.81 (dt, J ¼ 7.8, 1.0 Hz, 1H, AreH), 7.56 (td, J ¼ 8.0, 5.8 Hz, 1H, AreH),
7.42e7.31 (m, 1H, AreH), 7.25 (dd, J ¼ 7.8, 1.6 Hz, 1H, AreH), 7.11 (td,
J ¼ 7.7, 1.6 Hz, 1H, AreH), 6.91 (dd, J ¼ 8.1, 1.4 Hz, 1H, AreH), 6.85 (td,
4.1.1.1. (E)-2-(Benzylideneamino)phenol (1). Yield 85%, pale white
solid, m.p. 88e89 ꢅC; IR (KBr)
n
2924.32, 2319.87, 1626.93, 1482.50,
1401.37, 1250.65, 1125.20, 1098.78, 764.98, 689.28 cmꢀ1 1H NMR
(500 MHz, CDCl3) 8.70 (s, 1H, CH]N), 8.01e7.86 (m, 2H, AreH),
J ¼ 7.6, 1.4 Hz, 1H). 13C NMR (125 MHz, DMSO-d6)
d 161.97, 158.20,
.
151.95, 139.41, 137.62, 131.13, 128.36, 126.06, 119.93, 119.47, 118.35,
d
116.64, 114.69. ESI-MS m/z: 216.1 [M þ H]þ; HRMS: calcd for
7.59e7.42 (m, 3H, AreH), 7.36e7.27 (m, 1H, AreH), 7.22e7.15 (m,
1H, AreH), 7.02 (d, J ¼ 8.0 Hz, 1H, AreH), 6.95e6.85 (m, 1H, AreH).
C
13H11FNO [M þ H]þ, 216.0819, found 216.0819.
13C NMR (125 MHz, CDCl3)
d
157.13, 152.38, 135.93, 135.56, 131.68,
4.1.1.7. (E)-2-((4-Fluorobenzylidene)amino)phenol (7). Yield 75%,
light yellow solid, m.p. 86e88 ꢅC; IR (KBr)
2088.22, 1633.80,
1511.49, 1484.66, 1402.99, 1243.96, 1197.59, 1150.22, 1096.65,
1833.55, 753.72 cmꢀ1. 1H NMR (500 MHz, CDCl3)
8.66 (s, 1H, CH]
128.95, 128.88, 128.82, 120.11, 115.86, 115.04. ESI-MS m/z: 198.1
[M þ H]þ; HRMS: calcd for C13H12NO [M þ H]þ, 198.0913, found
198.0911.
n
d
N), 7.92 (ddd, J ¼ 8.6, 5.6, 2.6 Hz, 2H, AreH), 7.28 (dd, J ¼ 7.9, 2.7 Hz,
1H, AreH), 7.19 (qd, J ¼ 10.0, 8.8, 5.3 Hz, 4H, AreH), 7.02 (dd, J ¼ 8.1,
2.7 Hz, 1H, AreH), 6.91 (td, J ¼ 7.7, 2.5 Hz, 1H, AreH). 13C NMR
4.1.1.2. (E)-2-((2-Hydroxybenzylidene)amino)phenol (2). Yield 78%,
red solid, m.p. 191e192 ꢅC; IR (KBr)
n
2026.29, 1632.31, 1530.02,
1486.68, 1463.01, 1401.52, 1275.86, 1223.37, 1139.51, 764.38,
741.84 cmꢀ1. 1H NMR (500 MHz, DMSO-d6)
13.77 (s, 1H, OH), 9.71
(125 MHz, CDCl3)
d 157.13, 152.38, 135.93, 135.56, 131.68, 128.95,
d
128.88, 128.82, 120.11, 115.86, 115.04. ESI-MS m/z: 216.1 [M þ H]þ;
(s, 1H, OH), 8.96 (s, 1H, CH]N), 7.61 (dd, J ¼ 7.7, 1.7 Hz, 1H, AreH),
7.41e7.33 (m, 2H, AreH), 7.15e7.10 (m, 1H, AreH), 6.99e6.91 (m,
3H, AreH), 6.88 (td, J ¼ 7.6, 1.3 Hz, 1H, AreH). 13C NMR (125 MHz,
HRMS: calcd for C13H11FNO [M þ H]þ, 216.0819, found 216.0820.
4.1.1.8. (E)-4-(((2-Hydroxyphenyl)imino)methyl)benzene-1,3-diol
DMSO-d6)
d
161.64, 160.63, 150.99, 134.96, 132.72, 132.20, 127.91,
(8). Yield 65%, light yellow solid, m.p. 125 ꢅC; IR (KBr)
n
2923.92,
2026.36, 1627.05, 1589.11, 1455.52, 1401.44, 1384.01, 1247.28,
1124.52, 786.74, 755.93, 683.51, 605.68 cmꢀ1 1H NMR (500 MHz,
DMSO-d6) 9.63 (s, 1H, OH), 8.97 (s, 1H, OH), 8.59 (s, 1H, CH]N),
119.57, 119.52, 119.46, 118.63, 116.60, 116.46. ESI-MS m/z: 212.1
[M ꢀ H]ꢀ; HRMS: calcd for C13H10NO2 [M ꢀ H]ꢀ, 212.0717, found
212.0714.
.
d
7.47e7.37 (m, 2H, AreH), 7.30 (t, J ¼ 7.8 Hz, 1H, AreH), 7.15 (dd,
J ¼ 7.7, 1.6 Hz, 1H, AreH), 7.07 (td, J ¼ 7.7, 1.6 Hz, 1H, AreH), 6.91
(ddd, J ¼ 15.8, 8.0, 1.9 Hz, 2H, AreH), 6.82 (td, J ¼ 7.6, 1.4 Hz, 1H, Are
4.1.1.3. (E)-2-((3-Hydroxybenzylidene)amino)phenol (3). Yield 75%,
dark yellow solid, m.p. 215e216 ꢅC; IR (KBr)
n 3202.40, 1637.18,
1579.88, 1494.34, 1466.45, 1351.71, 1309.31, 1273.61, 1245.80,
H). 13C NMR (125 MHz, DMSO-d6)
d 160.08, 158.09, 151.38, 138.71,
1174.31,1118.09, 794.23, 733.38 cmꢀ1. 1H NMR (500 MHz, DMSO-d6)
138.23, 130.09, 127.59, 120.77, 119.94, 119.85, 118.96, 116.46, 115.16.
ESI-MS m/z: 228.1 [M ꢀ H]ꢀ; HRMS: calcd for C13H10NO3 [M ꢀ H]ꢀ,
228.0666, found 228.0665.
d
14.21 (s, 1H, OH), 10.14 (s, 1H, OH), 9.63 (s, 1H, CH]N), 8.77 (s, 1H,
AreH), 7.37 (d, J ¼ 8.5 Hz,1H, AreH), 7.30 (dd, J ¼ 8.0,1.6 Hz,1H, Are
H), 7.07 (td, J ¼ 7.6,1.6 Hz,1H, AreH), 6.94 (dd, J ¼ 8.0,1.4 Hz,1H, Are
H), 6.85 (td, J ¼ 7.6,1.4 Hz,1H, AreH), 6.35 (dd, J ¼ 8.4, 2.2 Hz,1H, Are
H), 6.24 (d, J ¼ 2.3 Hz, 1H, AreH). 13C NMR (125 MHz, DMSO-d6)
4.1.1.9. (E)-4-(((2-Hydroxyphenyl)imino)methyl)benzene-1,2-diol
(9). Yield 55%, red solid, m.p. 188e190 ꢅC; IR (KBr)
n 3280.68,
d
165.23,162.89,160.88,150.95,135.21,134.59,127.50,120.08,119.66,
2715.09, 2562.30, 1635.81, 1564.80, 1495.10, 1445.20, 1397.83,
116.85, 112.78, 107.99, 103.14. ESI-MS m/z: 212.1 [M ꢀ H]ꢀ; HRMS:
1300.99, 1283.82, 1173.21, 1160.54, 804.67, 769.71, 748.84 cmꢀ1. 1H
calcd for C13H10NO2 [M ꢀ H]ꢀ, 212.0717, found 212.0715.
NMR (500 MHz, DMSO-d6)
d 9.39 (s, 2H, OH), 8.85 (s, 1H, OH), 8.44
(s,1H, CH]N), 7.47 (d, J ¼ 2.0 Hz,1H, AreH), 7.25 (dd, J ¼ 8.3, 2.0 Hz,
1H, AreH), 7.10 (dd, J ¼ 7.7, 1.6 Hz, 1H, AreH), 7.02 (td, J ¼ 7.6, 1.6 Hz,
1H, AreH), 6.90e6.82 (m, 2H, AreH), 6.80 (t, J ¼ 7.6 Hz, 1H, AreH).
4.1.1.4. (E)-2-((4-Hydroxybenzylidene)amino)phenol (4). Yield 53%,
dark yellow solid, m.p. 163e165 ꢅC; IR (KBr)
n
2311.09, 1629.83,
1513.49, 1469.62, 1401.43, 1267.91, 1222.44, 1099.40, 765.71,
742.60 cmꢀ1. 1H NMR (500 MHz, DMSO-d6):
10.13 (s, 1H, OH), 8.81
13C NMR (125 MHz, DMSO-d6)
d 159.11, 150.71, 149.00, 145.47,
d
138.59, 128.30, 126.36, 122.35, 119.38, 118.93, 115.61, 115.31, 114.75.
ESI-MS m/z: 228.1 [M ꢀ H]ꢀ; HRMS: calcd for C13H10NO3 [M ꢀ H]ꢀ,
228.0666, found 228.0664.
(s, 1H, OH), 8.54 (s, 1H, CH]N), 7.86 (d, J ¼ 8.5 Hz, 2H, AreH), 7.13
(dd, J ¼ 7.6, 1.2 Hz, 1H, AreH), 7.05e7.01 (m, 1H, AreH), 6.89e6.86
(m, 3H, AreH), 6.82e6.79 (m, 1H, AreH). 13C NMR (125 MHz,
DMSO-d6):
d
161.05, 159.18, 151.51, 138.80, 131.45, 128.31, 127.08,
4.1.1.10. (E)-2-((4-(Dimethylamino)benzylidene)amino)phenol (10).
120.04, 119.17, 116.21, 116.02. ESI-MS m/z: 212.1 [M ꢀ H]ꢀ; HRMS:
Yield 42%, yellow solid, m.p. 121e122 ꢅC; IR (KBr)
n
2906.70,
2818.38, 1614.68, 1587.91, 1537.52, 1485.03, 1374.95, 1245.54,
1230.85, 1170.60, 1150.57, 811.24, 750.86, 739.60 cmꢀ1 1H NMR
(500 MHz, DMSO-d6) 8.69 (s, 1H, OH), 8.52 (s, 1H, CH]N), 7.91e
calcd for C13H10NO2 [M ꢀ H]ꢀ, 212.0717, found 212.071.
.
4.1.1.5. (E)-2-((2-Fluorobenzylidene)amino)phenol (5). Yield 70%,
d
light yellow solid, m.p. 105 ꢅC; IR (KBr)
n
2311.29, 1619.78, 1586.13,
1488.44, 1455.19, 1384.28, 1215.37, 1202.92, 1091.32, 763.02,
755.45 cmꢀ1. 1H NMR (500 MHz, DMSO-d6)
9.14 (s, 1H, OH), 8.90
7.78 (m, 2H, AreH), 7.16 (dd, J ¼ 7.9, 1.6 Hz, 1H, AreH), 7.03 (td,
J ¼ 7.7, 1.6 Hz, 1H, AreH), 6.87 (dd, J ¼ 8.0, 1.4 Hz, 1H, AreH),
6.82e6.78 (m, 3H, AreH), 3.04 (s, 6H, N(CH3)2). 13C NMR
d
(s, 1H, CH]N), 8.32 (td, J ¼ 7.8, 1.9 Hz, 1H, AreH), 7.62e7.53 (m, 1H,
AreH), 7.38e7.31 (m, 2H, AreH), 7.23 (dd, J ¼ 7.8, 1.6 Hz, 1H, AreH),
7.14e7.07 (m,1H, AreH), 6.93 (dd, J ¼ 8.1,1.4 Hz,1H, AreH), 6.85 (td,
(125 MHz, DMSO-d6) d 158.49, 152.26, 150.91, 138.50, 131.43,
130.40, 126.10, 124.10, 119.35, 115.38, 111.30, 41.20. ESI-MS m/z:
241.1 [M þ H]þ; HRMS: calcd for C13H10NO3 [M þ H]þ, 241.1335,
found 241.1336.
J ¼ 7.6, 1.4 Hz, 1H, AreH). 13C NMR (125 MHz, DMSO-d6)
d 161.57,
152.28, 151.63,138.24,133.79,133.72,128.68,128.25,125.20,120.22,
120.03, 116.69, 116.33. ESI-MS m/z: 216.1 [M þ H]þ; HRMS: calcd for
4.1.1.11. (E)-2-((4-Methoxybenzylidene)amino)phenol
(11).
C
13H11FNO [M þ H]þ, 216.0819, found 216.0817.
Yield 60%, yellow solid, m.p. 90e92 ꢅC; IR (KBr)
n
2969.79, 2925.81,