Molecules 2020, 25, 2593
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J = 8.1 Hz, ArH), 7.47–7.59 (m, 4H, ArH), 7.85 (d, 2H, J = 8.9 Hz, ArH), 8.71 (s, 1H, -CH=N-), 8.77, 10.06
(2s, 2H, 2NH, exchangeable with D2O), 12.56 (s, 1H, NH). Anal. Calcd. (%) for C30H32N6O2 (508.61):
C, 70.84; H, 6.34; N, 16.52. Found: C, 70.90; H, 6.25; N, 16.43.
N-(p-Chlorophenyl)-3-(p-methoxyphenylamino)-5-(4-(piperidin-1-yl)benzylideneamino)-1H-pyrazole-4-
carboxamide (8d): Yellow crystals; melting point: 268–270 ◦C; yield: 81 %. IR (KBr) max/cm−1 3365
ν
(NH), 1657 (C=O). 1H-NMR (300 MHz)
δ ppm: 1.62 (s, 6H, piperidine moiety), 3.45 (s, 4H, piperidine
moiety), 3.72 (s, 3H, OCH3), 6.89 (d, 2H, J = 9.0 Hz, ArH), 7.11 (d, 2H, J = 9.2 Hz, ArH), 7.42 (d, 2H,
J = 8.9 Hz, ArH), 7.46 (d, 2H, J = 9.3 Hz, ArH), 7.70 (d, 2H, J = 8.9 Hz, ArH), 7.85 (d, 2H, J = 8.9 Hz,
ArH), 8.64 (s, 1H, -CH=N-), 8.80, 10.24 (2s, 2H, 2NH, exchangeable with D2O), 12.30 (s, 1H, NH). Anal.
Calcd. (%) for C29H29ClN6O2 (529.03): C, 65.84; H, 5.53; N, 15.89. Found: C, 65.65; H, 5.48; N, 15.71.
3-(p-Methoxyphenylamino)-5-(3,4,5-trimethoxybenzylideneamino)-1H-pyrazole-4-carboxamide (9a): Yellow
crystals; Melting point: 222–224 ◦C; Yield: 73 %. IR (KBr) max/cm−1 3373, 3142 (NH, NH2), 1654 (C=O).
ν
1H-NMR (300 MHz)
δ ppm: 3.72, 3.77, 3.87 (3s, 12H, 4OCH3), 6.82 (d, 2H, J = 9.0 Hz, ArH), 6.89 (d, 2H,
J = 8.9 Hz, ArH), 7.25–7.46 (m, 4H, 2H of ArH & 2H of NH2-amide exchangeable with D2O), 8.85 (s,
2H, -CH=N- & NH exchangeable with D2O), 12.12 (s, 1H, NH, exchangeable with D2O). 13C-NMR
(76 MHz) δ ppm: 55.04, 56.11, 60.28 (4C, 4OCH3), 92.17, 104.26, 115.34, 121.14, 133.85, 141.73, 153.43,
154.64, 160.12 (16C), 162.51 (C=O). MS (m/z, %): 425 (M+, 46.11). Anal. Calcd. (%) for C21H23N5O5
(425.44): C, 59.29; H, 5.45; N, 16.46. Found: C, 59.25; H, 5.59; N, 16.54.
3-(p-Methoxyphenylamino)-N-phenyl-5-(3,4,5-trimethoxybenzylideneamino)-1H-pyrazole-4-carboxamide (9b):
Yellow crystals; melting point: 221–223 ◦C; yield: 72 %. IR (KBr) max/cm−1 3446, 3294 (NH), 1652
ν
(C=O). 1H-NMR (300 MHz)
7.07 (t, 1H, ArH), 7.32–7.42 (m, 6H, ArH), 7.68 (d, 2H, J = 7.5 Hz, ArH), 8.69 (s, 1H, -CH=N-), 9.01,
10.05, 12.64 (3s, 3H, 3NH, exchangeable with D2O). 13C-NMR (76 MHz)
ppm: 55.09, 56.81, 60.62 (4C,
δ ppm: 3.74, 3.79, 3.92 (3s, 12H, 4OCH3), 6.91 (d, 2H, J = 9.0 Hz, ArH),
δ
4OCH3), 92.37, 104.42, 114.19, 121.09, 126.37, 128.04, 129.28, 132.58, 137.04, 141.55, 153.73, 154.68, 161.80
(22C), 162.90 (C=O). MS (m/z, %): 500 (M+-1, 15.28). Anal. Calcd. (%) for C27H27N5O5 (501.53): C,
64.66; H, 5.43; N, 13.96. Found: C, 64.42; H, 5.58; N, 14.12.
3-(p-Methoxyphenylamino)-N-p-tolyl-5-(3,4,5-trimethoxybenzylideneamino)-1H-pyrazole-4-carboxamide (9c):
Yellow crystals, melting point: 234–236 ◦C; yield: 79%. IR (KBr) max/cm−1 3437, 3285 (NH), 1655
ν
(C=O). 1H-NMR (300 MHz)
J = 8.1 Hz, ArH), 7.15 (d, 2H, J = 8.3 Hz, ArH), 7.40–7.59 (m, 6H, ArH), 8.70 (s, 1H, -CH=N-), 8.96, 9.95,
12.64 (3s, 3H, 3NH, exchangeable with D2O). 13C-NMR (76 MHz)
ppm: 21.31 (CH3), 55.04, 56.79,
δ ppm: 2.27 (s, 3H, CH3), 3.73, 3.79, 3.92 (3s, 12H, 4OCH3), 6.91 (d, 2H,
δ
60.65 (4C, 4OCH3), 91.93, 104.26, 114.17, 121.14, 126.46, 129.37, 132.54, 136.85, 141.57, 153.74, 154.40,
161.74 (22C), 162.88 (C=O). MS (m/z, %): 515 (M+, 24.80). Anal. Calcd. (%) for C28H29N5O5 (515.56): C,
65.23; H, 5.67; N, 13.58. Found: C, 65.15; H, 5.79; N, 13.51.
N-(p-Chlorophenyl)-3-(p-methoxyphenylamino)-5-(3,4,5-trimethoxybenzylideneamino)-1H-pyrazole-4-
carboxamide (9d): Orange crystals; melting point: 213–215 ◦C; yield: 87%. IR (KBr) max/cm−1 3441,
ν
3289 (NH), 1650 (C=O). 1H-NMR (400 MHz)
8.9 Hz, ArH), 7.40–7.41 (m, 6H, ArH), 7.71 (d, 2H, J = 8.9 Hz, ArH), 8.65 (s, 1H, -CH=N-), 9.00, 10.10,
12.75 (3s, 3H, 3NH, exchangeable with D2O). 13C-NMR (101 MHz)
ppm: 55.26, 56.06, 60.31 (4C,
δ ppm: 3.73, 3.78, 3.90 (3s, 12H, 4OCH3), 6.90 (d, 2H, J =
δ
4OCH3), 92.30, 106.51, 114.45, 120.55, 126.68, 128.86, 130.21, 137.56, 141.64, 153.37, 154.07, 161.91 (22C),
162.72 (C=O). MS (m/z, %): 535 (M+, 19.89). Anal. Calcd. (%) for C27H26ClN5O5 (535.98): C, 60.50; H,
4.89; N, 13.07. Found: C, 60.37; H, 4.99; N, 12.91.
3.2. Biological Evaluation (See Supplementary Material)
The inhibition zones of pyrazole Schiff bases (6a–d, 7a–d, 8a–d, and 9a–d) and the minimal
inhibitory concentrations (MIC) of the potent Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) were performed
according to the conventional paper disk diffusion method [54,55,74].