´
M. Kratký et al.
European Journal of Pharmaceutical Sciences 159 (2021) 105732
8.05-8.01 (2H, m, H2, H6), 7.74 (1H, d, J = 8.1 Hz, H6′), 7.52-7.49 (2H,
m, H3, H5), 7.08-7.04 (2H, m, H3′, H5′), 3.86 (3H, s, Me). 13C NMR
(DMSO, 126 MHz): δ 165.94, 163.85, 161.26, 152.46, 138.24, 133.84,
130.77, 127.87, 121.90, 119.82, 118.68, 116.76, 52.34. Anal. Calcd. for
H6′), 7.50 (2H, d, J = 8.3 Hz, H3, H5), 7.44 (1H, td, J = 7.8, 1.7 Hz, H4′),
7.02-6.97 (2H, m, H3′, H5′), 4.32 (2H, q, J = 7.1 Hz, CH2), 1.33 (3H, t, J
= 7.1 Hz, Me). 13C NMR (DMSO, 126 MHz): δ 165.45, 165.03, 160.48,
152.64, 134.05, 132.75, 130.71, 128.00, 121.83, 121.78, 119.49,
116.87, 60.91, 14.34. Anal. Calcd. for C16H15NO3 (269.30): C, 71.36; H,
5.61; N, 5.20. Found: C, 71.22; H, 5.72; N, 5.06.
C
15H12ClNO3 (286.72): C, 62.19; H, 4.18; N, 4.83. Found: C, 62.30; H,
4.07; N, 4.91.
Methyl (E)-4-[(5-chloro-2-hydroxybenzylidene)amino]benzoate 4d.
Yellow solid; yield 83%; mp 190.9-192.0◦C. IR (ATR): 3076, 2963, 1719
(COO), 1619, 1599 (CH=N), 1563, 1478, 1433, 1349, 1311, 1283,
1276, 1184, 1169, 1104, 1015, 953, 873, 831, 786, 769, 715, 702, 655
cmꢀ 1. 1H NMR (500 MHz, DMSO-d6): δ 12.48 (1H, s, OH), 8.91 (1H, s,
CH=N), 8.00 (2H, d, J = 8.6 Hz, H2, H6), 7.74 (1H, d, J = 2.7 Hz, H6′),
7.47-7.41 (3H, m, H3, H5, H4′), 6.98 (2H, d, J = 8.7 Hz, H3′), 3.83 (3H,
s, Me). 13C NMR (DMSO, 126 MHz): δ 166.31, 163.68, 159.40, 153.04,
133.85, 131.32, 131.15, 128.32, 123.32, 122.26, 121.28, 119.30, 52.70.
Anal. Calcd. for C15H12ClNO3 (286.72): C, 62.19; H, 4.18; N, 4.83.
Found: C, 62.07; H, 4.29; N, 4.90.
Ethyl (E)-4-[(3-chloro-2-hydroxybenzylidene)amino]benzoate 5b.
Pale orange solid; yield 68%; mp 116.5-117.8◦C. IR (ATR): 2983, 1705
(COO), 1618, 1594 (CH=N), 1565, 1446, 1366, 1307, 1273, 1238,
1206, 1183, 1168, 1141, 1125, 1105, 1025, 857, 835, 813, 736, 702,
691 cmꢀ 1. 1H NMR (500 MHz, DMSO-d6): δ 13.94 (1H, s, OH), 9.07 (1H,
s, CH=N), 8.07-8.02 (2H, m, H2, H6), 7.67-7.56 (4H, m, H3, H5, H4′,
H6′), 7.01 (1H, t, J = 7.8 Hz, H5′), 4.32 (2H, q, J = 7.1 Hz, CH2), 1.33
(3H, t, J = 7.1 Hz, Me). 13C NMR (DMSO, 126 MHz): δ 165.36, 165.31,
156.68, 151.04, 133.82, 132.24, 130.74, 128.55, 122.01, 120.57,
120.18, 119.87, 60.99, 14.33. Anal. Calcd. for C16H14ClNO3 (303.74): C,
63.27; H, 4.65; N, 4.61. Found: C, 63.14; H, 4.59; N, 4.88.
Methyl (E)-4-[(2-hydroxy-5-iodobenzylidene)amino]benzoate 4e.
Yellow solid; yield 86%; mp 221.7-223.3◦C. IR (ATR): 2949, 1708
(COO), 1616, 1596 (CH=N), 1557, 1470, 1433, 1347, 1310, 1280,
1181, 1169, 1103, 1015, 983, 954, 914, 868, 861, 845, 825, 784, 768,
703, 696 cmꢀ 1. 1H NMR (500 MHz, DMSO-d6): δ 13.12 (1H, s, OH), 8.99
(1H, s, CH=N), 8.08-8.03 (3H, m, H2, H6, H6′), 7.67 (1H, dd, J = 8.7,
2.4 Hz, H4′), 7.58-7.54 (2H, m, H3, H5), 6.83 (1H, d, J = 8.7 Hz, H3′),
3.87 (3H, s, Me). 13C NMR (DMSO, 126 MHz): δ 166.24, 163.58, 160.27,
152.97, 142.16, 140.27, 131.08, 128.20, 122.44, 122.20, 119.94, 81.37,
52.64. Anal. Calcd. for C15H12INO3 (381.17): C, 47.27; H, 3.17; N, 3.67.
Found: C, 46.99; H, 3.21; N, 3.81.
Ethyl (E)-4-[(4-chloro-2-hydroxybenzylidene)amino]benzoate 5c.
Yellow-orange solid; yield 76%; mp 131.2-132.3◦C. IR (ATR): 3001,
1715 (COO), 1620, 1593 (CH=N), 1558, 1507, 1367, 1270, 1175, 1166,
1097, 1080, 1014, 933, 842, 858, 799, 771, 690 cmꢀ 1
.
1H NMR (500
MHz, DMSO-d6): δ 12.98 (1H, s, OH), 8.99 (1H, s, CH=N), 8.04-8.00
(2H, m, H2, H6), 7.73 (1H, d, J = 8.0 Hz, H6′), 7.52-7.48 (2H, m, H3,
H5), 7.08-7.03 (2H, m, H3′, H5′), 4.32 (2H, q, J = 7.1 Hz, CH2), 1.33
(3H, t, J = 7.1 Hz, Me). 13C NMR (DMSO, 126 MHz): δ 165.43, 163.77,
161.27, 152.36, 138.23, 133.84, 130.72, 128.15, 121.85, 119.81,
118.66, 116.76, 60.94, 14.34. Anal. Calcd. for C16H14ClNO3 (303.74): C,
63.27; H, 4.65; N, 4.61. Found: C, 63.36; H, 4.72; N, 4.49.
Methyl
(E)-4-[(3-bromo-5-chloro-2-hydroxybenzylidene)amino]
Ethyl (E)-4-[(5-chloro-2-hydroxybenzylidene)amino]benzoate 5d.
Orange solid; yield 82%; mp 144.8-146.1◦C. IR (ATR): 2981, 1699
(COO), 1598 (CH=N), 1564, 1484, 1363, 1284, 1188, 1169, 1127,
benzoate 4f. Orange solid; yield 82%; mp 174.5-176.5◦C. IR (ATR):
3069, 2957, 1703 (COO), 1596 (CH=N), 1561, 1452, 1433, 1414, 1363,
1294, 1206, 1191, 1166, 1121, 1016, 971, 873, 858, 772, 739, 726, 712,
694 cmꢀ 1. 1H NMR (500 MHz, DMSO-d6): δ 14.10 (1H, s, OH), 9.03 (1H,
s, CH=N), 8.07-8.04 (2H, m, H2, H6), 7.88 (1H, d, J = 2.6 Hz, H4′), 7.79
(1H, d, J = 2.6 Hz, H6′), 7.60-7.56 (2H, m, H3, H5), 3.87 (3H, s, Me). 13C
NMR (DMSO, 126 MHz): δ 165.82, 164.34, 156.86, 150.57, 135.67,
131.81, 130.83, 128.57, 122.89, 122.10, 120.41, 111.37, 52.41. Anal.
Calcd. for C15H11BrClNO3 (386.61): C, 48.88; H, 3.01; N, 3.80. Found: C,
48.74; H, 3.13; N, 3.77.
1111, 1024, 871, 855, 773, 714, 696, 650, 635 cmꢀ 1
.
1H NMR (500
MHz, DMSO-d6): δ 12.49 (1H, s, OH), 8.91 (1H, s, CH=N), 8.01-7.98
(2H, m, H2, H6), 7.75 (1H, d, J = 2.6 Hz, H6′), 7.46-7.41 (3H, m, H3,
H5, H4′), 6.98 (1H, d, J = 8.9 Hz, H3′), 4.28 (2H, q, J = 7.1 Hz, CH2),
1.29 (3H, t, J = 7.2 Hz, Me). 13C NMR (DMSO, 126 MHz): 165.80,
163.62, 159.40, 152.97, 133.83, 131.31, 131.10, 128.60, 123.32,
122.22, 121.27, 119.28, 61.31, 14.70. Anal. Calcd. for C16H14ClNO3
(303.74): C, 63.27; H, 4.65; N, 4.61. Found: C, 63.11; H, 4.79; N, 4.70.
Ethyl (E)-4-[(2-hydroxy-5-iodobenzylidene)amino]benzoate 5e. Or-
ange solid; yield 79%; mp 154.2-156.1◦C. IR (ATR): 3001, 1717 (COO),
1592 (CH=N), 1556, 1475, 1369, 1353, 1272, 1221, 1169, 1096, 1013,
Methyl (E)-4-[(5-chloro-2-hydroxy-3-iodobenzylidene)amino]ben-
zoate 4g. Pale orange solid; yield 89%; mp 182.1-183.9◦C. IR (ATR):
3071, 1713 (COO), 1592 (CH=N), 1551, 1436, 1359, 1290, 1277, 1202,
1163, 1102, 873, 773, 738, 719, 703, 691 cmꢀ 1
.
1H NMR (500 MHz,
873, 860, 811, 785, 771, 691 cmꢀ 1
.
1H NMR (500 MHz, DMSO-d6): δ
DMSO-d6): δ 14.20 (1H, s, OH), 8.95 (1H, s, CH=N), 8.06-8.03 (2H, m,
H2, H6), 7.97 (1H, d, J = 2.5 Hz, H4′), 7.77 (1H, d, J = 2.6 Hz, H6′),
7.59-7.55 (2H, m, H3, H5), 3.86 (3H, s, Me). 13C NMR (DMSO, 126
MHz): δ 165.81, 164.27, 159.31, 150.52, 141.29, 132.52, 130.81,
128.51, 123.35, 122.10, 119.22, 87.49, 52.40. Anal. Calcd. for
13.15 (1H, s, OH), 9.00 (1H, s, CH=N), 8.08-8.02 (3H, m, H2, H6, H6′),
7.66 (1H, dd, J = 8.7, 2.3 Hz, H4′), 7.59-7.54 (2H, m, H3, H5), 6.84 (1H,
d, J = 8.7 Hz, H3′), 4.33 (2H, q, J = 7.1 Hz, CH2), 1.33 (3H, t, J = 7.1 Hz,
Me). 13C NMR (DMSO, 126 MHz): δ 165.42, 163.22, 159.98, 152.59,
141.84, 139.98, 130.73, 128.18, 122.13, 121.86, 119.63, 81.07, 60.95,
14.34. Anal. Calcd. for C16H14INO3 (395.20): C, 48.63; H, 3.57; N, 3.54.
Found: C, 48.70; H, 3.44; N, 3.70.
C
15H11ClINO3 (415.61): C, 43.35; H, 2.67; N, 3.37. Found: C, 43.50; H,
2.58; N, 3.49.
Methyl (E)-4-[(2-hydroxy-3,5-diiodobenzylidene)amino]benzoate
4h. Orange solid; yield 90%; mp 224.1-226.5◦C. IR (ATR): 3061, 2952,
1703 (COO), 1585 (CH=N), 1542, 1437, 1353, 1311, 1292, 1275, 1205,
1158, 1117, 1103, 950, 869, 864, 776, 739, 695, 706, 695, 659 cmꢀ 1. 1H
NMR (500 MHz, THF-d8): δ 14.10 (1H, s, OH), 8.77 (1H, s, CH=N), 8.22-
8.07 (3H, m, H2, H6, H4′), 7.92-7.89 (1H, m, H6′), 7.51-7.46 (2H, m,
H3, H5), 3.89 (3H, s, Me). 13C NMR (DMSO, 126 MHz): δ 166.38,
164.20, 161.36, 152.13, 150.45, 142.24, 131.71, 130.13, 122.31,
121.78, 87.56, 80.60, 52.18. Anal. Calcd. for C15H11I2NO3 (507.07): C,
35.53; H, 2.19; N, 2.76. Found: C, 35.70; H, 2.12; N, 2.83.
Ethyl (E)-4-[(3-bromo-5-chloro-2-hydroxybenzylidene)amino]ben-
zoate 5f. Orange solid; yield 75%; mp 160.5-162.7◦C. IR (ATR): 3067,
2988, 1698 (COO), 1595 (CH=N), 1557, 1449, 1413, 1362, 1250, 1199,
1166, 1123, 1106, 1023, 869, 857, 773, 741, 722, 697 cmꢀ 1. 1H NMR
(500 MHz, DMSO-d6): δ 14.09 (1H, s, OH), 9.03 (1H, s, CH=N), 8.08-
8.03 (2H, m, H2, H6), 7.88 (1H, d, J = 2.6 Hz, H4′), 7.79 (1H, d, J =
2.6 Hz, H6′), 7.60-7.55 (2H, m, H3, H5), 4.33 (2H, q, J = 7.2 Hz, CH2),
1.33 (3H, t, J = 7.1 Hz, Me). 13C NMR (DMSO, 126 MHz): δ 165.32,
164.26, 156.91, 150.51, 135.66, 131.79, 130.78, 128.84, 122.85,
122.06, 120.41, 111.40, 61.04, 14.33. Anal. Calcd. for C16H13BrClNO3
(382.64): C, 50.22; H, 3.42; N, 3.66. Found: C, 50.28; H, 3.59; N, 3.40.
Ethyl (E)-4-[(5-chloro-2-hydroxy-3-iodobenzylidene)amino]benzo-
ate 5g. Orange solid; yield 74%; mp 184-186.5◦C. IR (ATR): 3064, 2981,
1698 (COO), 1590 (CH=N), 1550, 1429, 1367, 1358, 1300, 1199, 1162,
Ethyl (E)-4-[(2-hydroxybenzylidene)amino]benzoate 5a. Yellow
solid; yield 71%; mp 87.9-89.2◦C (85-86.5◦C, Kuder et al., 1975). IR
(ATR): 2976, 1705 (COO), 1619, 1598 (CH=N), 1573, 1284, 1269,
1188, 1166, 1099, 1012, 912, 855, 840, 815, 787, 768, 751, 739, 699,
680 cmꢀ 1. 1H NMR (500 MHz, DMSO-d6): δ 12.65 (1H, s, OH), 8.98 (1H,
s, CH=N), 8.02 (2H, d, J = 8.2 Hz, H2, H6), 7.70 (1H, dd, J = 7.7, 1.8 Hz,
1099, 1016, 876, 854, 774, 740, 717, 694 cmꢀ 1
.
1H NMR (500 MHz,
DMSO-d6): δ 14.23 (1H, s, OH), 8.96 (1H, s, CH=N), 8.07-8.03 (2H, m,
5