1890
Biol. Pharm. Bull.
Vol. 40, No. 11 (2017)
with 65–83% yield.
νcm−1): 3170 (NH) and 1658 (C=O); 1H-NMR (DMSO-d6)
6-(4-Bromophenyl)-N′-(2,4-dichlorobenzylidene)-2- δ ppm: 2.52, 2.65 (2s, 3H, CH3), 7.04, 7.15 (2t, 1H, Ar-H,
methylnicotinohydrazide (8a)
J=4.40 & 4.76Hz), 7.37, 7.48 (2d, 1H, Ar-H, J=3.00 &
2.64Hz), 7.69–7.72 (m, 3H, Ar-H), 7.81–7.98 (m, 2H, Ar-H),
White crystals (yield 70%), mp 269–271°C.30)
6-(4-Bromophenyl)-N′-(2,6-dichlorobenzylidene)-2- 8.09 (d, 2H, Ar-H, J=8.52Hz), 8.28, 8.53 (2s, 1H, Ar-H),
methylnicotinohydrazide (8b)
11.87, 11.95 (2s, 1H, NH, D2O exchangeable); 13C-NMR
White crystals (yield 73%), mp 261–263°C; IR (KBr, (DMSO-d6) δ ppm: 23.45, 23.55 (CH3), 117.12, 117.58, 123.46,
νcm−1): 3167 (NH) and 1651 (C=O); 1H-NMR (DMSO-d6) 123.67, 128.31, 128.39, 129.00, 129.18, 129.26, 129.60, 129.70,
δ ppm: 2.53, 2.65 (2s, 3H, CH3), 7.35–7.42 (m, 3H, Ar-H), 130.25, 130.93, 131.73, 132.25, 137.35, 137.53, 137.60, 137.69,
7.71 (d, 2H, Ar-H, J=8.40Hz), 7.85–8.00 (m, 2H, Ar-H), 139.15, 139.33, 139.82, 143.48, 154.77, 155.15, 155.49, 156.47,
8.09 (d, 2H, Ar-H, J=8.48Hz), 8.34, 8.62 (2s, 1H, Ar-H), 164.21, 170.08; Anal. Calcd for C18H14BrN3OS: C, 54.01; H,
11.96, 12.03 (2s, 1H, NH, D2O exchangeable); Anal. Calcd for 3.53; N, 10.50. Found: C, C, 53.82; H, 3.56; N, 10.33.
C20H14BrCl2N3O: C, 51.87; H, 3.05; N, 9.07. Found: C, 51.54;
H, 3.09; N, 9.15.
6-(4-Bromophenyl)-2-methyl-N′-(pyridin-3-ylmethylene)-
nicotinohydrazide (8g)
6-(4-Bromophenyl)-N′-(3,4-dimethoxybenzylidene)-2-
methylnicotinohydrazide (8c)
White crystals (yield 80%), mp 247–249°C; IR (KBr,
νcm−1): 3190 (NH) and 1662 (C=O); 1H-NMR (DMSO-d6)
White crystals (yield 83%), mp 233–235°C; IR (KBr, δ ppm: 2.53, 2.66 (2s, 3H, CH3), 7.34, 7.48 (2dd, 1H, Ar-H,
νcm−1): 3150 (NH) and 1651 (C=O); 1H-NMR (DMSO-d6) J=7.76, 4.84Hz), 7.70 (d, 2H, Ar-H, J=8.44Hz), 7.85–8.01 (m,
δ ppm: 2.53, 2.65 (2s, 3H, CH3), 3.58, 3.72, 3.81 (3s, 6H, 2H, Ar-H), 8.10 (d, 2H, Ar-H, J=8.44Hz), 8.15 (d, 1H, Ar-H,
2-OCH3), 6.92–7.20 (m, 2H, Ar-H), 7.37 (s, 1H, Ar-H), 7.70 J=8.56Hz), 8.38 (s, 1H, Ar-H), 8.62 (d, 1H, Ar-H, J=4.80Hz),
(d, 2H, Ar-H, J=8.44Hz), 7.85–8.00 (m, 2H, Ar-H), 8.09 (d, 8.88 (s, 1H, Ar-H), 12.09, 12.16 (2s, 1H, NH, D2O exchange-
2H, Ar-H, J=8.52Hz), 8.24 (s, 1H, Ar-H), 11.80, 11.91 (2s, able); 13C-NMR (DMSO-d6) δ ppm: 23.42, 23.49 (CH3), 117.22,
1H, NH, D2O exchangeable); 13C-NMR (DMSO-d6) δ ppm: 117.58, 123.49, 123.70, 124.40, 124.49, 129.22, 129.27, 129.45,
23.43 (CH3), 55.52, 55.92 (OCH3), 55.98, 56.04 (OCH3), 108.73, 130.23, 130.29, 130.52, 132.20, 132.25, 133.54, 134.03, 137.42,
109.28, 111.93, 112.10, 117.06, 117.58, 120.89, 122.49, 123.41, 137.51, 137.66, 142.09, 145.72, 148.78, 149.30, 150.97, 151.33,
123.63, 127.25, 129.11, 129.24, 129.85, 132.24, 137.31, 137.51, 154.86, 155.08, 155.58, 156.54, 164.50, 170.52; Anal. Calcd for
137.56, 137.79, 144.24, 148.58, 149.26, 149.55, 150.88, 151.35, C19H15BrN4O: C, 57.74; H, 3.83; N, 14.17. Found: C, 58.08; H,
154.72, 155.16, 155.41, 156.40, 164.21, 170.21; Anal. Calcd for 3.87; N, 14.08.
C22H20BrN3O3: C, 58.16; H, 4.44; N, 9.25. Found: C, 58.34; H,
4.48; N, 9.16.
5-Bromo-2-(2-(4-chlorophenyl)-2-oxoethoxy)benzalde-
hyde 11 To a stirred mixture of 5-bromosalicylaldehyde 9
6-(4-Bromophenyl)-N′-(2,5-dimethoxybenzylidene)-2- (0.2g, 1mmol) and anhydrous potassium carbonate (0.27g,
methylnicotinohydrazide (8d) 2mmol) in absolute ethyl alcohol, a solution of 2-bromo-1-
White crystals (yield 80%), mp 235–237°C; IR (KBr, (4-chlorophenyl)ethan-1-one 10 (0.23g, 1mmol) in absolute
νcm−1): 3170 (NH) and 1662 (C=O); 1H-NMR (DMSO-d6) ethyl alcohol was added. The reaction mixture was stirred for
δ ppm: 2.52, 2.66 (2s, 3H, CH3), 3.51, 3.81 (2s, 3H, OCH3), 2h at room temperature. The solid product was collected by
3.77 (s, 3H, OCH3), 6.79–7.39 (m, 3H, Ar-H), 7.70 (d, 2 H, filtration, washed with water and ether, and crystallized from
Ar-H, J=8.52Hz), 7.83–8.00 (m, 2H, Ar-H), 8.10 (d, 2H, isopropanol to afford white crystals of compound 11 (yield
Ar-H, J=8.40Hz), 8.37, 8.65 (2s, 1H, Ar-H), 11.90, 11.96 (2s, 55%), mp 165–166°C; IR (KBr, νcm−1): 1670, 1715 (2C=O);
1H, NH, D2O exchangeable); 13C-NMR (DMSO-d6) δ ppm: 1H-NMR (DMSO-d6) δ ppm: 5.83 (2s, 2H, –OCH2–), 7.65 (d,
23.43, 23.50 (CH3), 55.46, 55.94 (OCH3), 56.64, 56.73 (OCH3), 2H, Ar-H, J=8.48Hz), 7.76–7.79 (m, 2H, Ar-H), 8.02 (d, 2H,
109.55, 109.94, 113.73, 113.95, 117.01, 117.10, 117.54, 118.42, Ar-H, J=8.72Hz), 8.07 (s, 1H, Ar-H), 10.41 (s, 1H, CHO);
123.11, 123.43, 123.65, 129.13, 129.27, 129.65, 130.60, 132.24, Anal. Calcd for C15H10BrClO3: C, 50.95; H, 2.85. Found: C,
137.39, 137.54, 139.83, 143.77, 152.51, 152.84, 153.42, 153.74, 51.27; H, 2.79.
154.72, 155.07, 155.46, 156.56, 164.23, 170.35; Anal. Calcd for
C22H20BrN3O3: C, 58.16; H, 4.44; N, 9.25. Found: C, 57.82; H, benzylidene)-6-(4-bromophenyl)-2-methylnicotinohydrazide
4.49; N, 9.18. 12 Compound 11 (0.35g, 1mmol) was added to a suspension
N′-(4-Bromo-2-hydroxybenzylidene)-6-(4-bromophenyl)-2- of 6-(4-bromophenyl)-2-methylnicotinohydrazide (0.31g,
methylnicotinohydrazide (8e) 1mmol) in absolute ethyl alcohol (10mL) and a catalytic
N′-(5-Bromo-2-(2-(4-chlorophenyl)-2-oxoethoxy)-
6
White crystals (yield 70%), mp 241–242°C; IR (KBr, amount of glacial acetic acid. The reaction mixture was heat-
νcm−1): 3182 (NH) and 1651 (C=O); 1H-NMR (DMSO-d6) ed under reflux for 2h. The solid formed was filtered, washed
δ ppm: 2.52, 2.67 (2s, 3H, CH3), 6.78, 6.90 (2d, 1H, Ar-H, with hot ethanol then crystallized from ethanol/DMF to fur-
J=8.68 & 8.76Hz), 7.31, 7.42 (2dd, 1H, Ar-H, J=8.68, nish the target compound 12 with (yield 64%), mp 236–238°C;
2.36Hz), 7.70 (d, 2H, Ar-H, J=8.40Hz), 7.82–7.96 (m, 2H, IR (KBr, νcm−1): 3155 (NH) and 1701 (C=O); 1H-NMR
Ar-H), 8.01 (d, 1H, Ar-H, J=8.04Hz), 8.09 (d, 2H, Ar-H, (DMSO-d6) δ ppm: 2.54, 2.67 (2s, 3H, CH3), 5.72, 5.74 (2s,
J=8.44Hz), 8.32, 8.51 (2s, 1H, Ar-H), 10.26, 11.14 (2s, 1H, 2H, –OCH2–), 7.02, 7.12 (2d, 1H, Ar-H, J=8.92 & 8.96Hz),
OH, D2O exchangeable), 12.09, 12.20 (2s, 1H, NH, D2O ex- 7.41, 7.53 (2dd, 1H, Ar-H, J=8.92, 2.48Hz), 7.53 (d, 2H, Ar-H,
changeable); Anal. Calcd for C20H15Br2N3O2: C, 49.11; H, J=8.44Hz), 7.70 (d, 2H, Ar-H, J=8.48Hz), 7.88–8.04 (m, 5H,
3.09; N, 8.59. Found: C, 48.83; H, 3.13; N, 8.68.
6-(4-Bromophenyl)-2-methyl-N′-(thiophen-2-ylmethylene)- Ar-H), 12.14 (s, 1H, NH, D2O exchangeable); Anal. Calcd for
nicotinohydrazide (8f) C28H20Br2ClN3O3: C, 52.41; H, 3.14; N, 6.55. Found: C, 52.18;
White crystals (yield 78%), mp 245–246°C; IR (KBr, H, 3.17; N, 6.69.
Ar-H), 8.10 (d, 2H, Ar-H, J=8.48Hz), 8.48, 8.73 (2s, 1H,