1134
Medicinal Chemistry Research (2021) 30:1125–1138
4-(4-Cinnamoyl-5-methyl-1H-1,2,3-triazol-1-yl)benzene-
(m, 10H, H-Ph), 7.66 (s, 2H, NH2), 7.89 (d, 2H, JH-H =
sulfonamide (4) was obtained as white solid (6.8 g, 86.4%);
mp 278–280 °C (EtOH/DMF); IR (KBr) Ʋmax 3403 (NH2),
7.8 Hz, H-Ar), 8.12 (d, 2H, JH-H = 7.8 Hz, H-Ar); 13C NMR
(300 MHz, DMSO):164.48, 157.99, 152.17, 150.73,
145.19, 140.73, 137.54, 136.93, 134.73, 129.09, 128.94,
128.80, 127.71, 127.21, 125.71, 125.69, 121.48, 120.89,
61.87, 44.66, 15.91, 10.15; IR (KBr) Ʋmax 3425 and 3325
(NH2) cm–1; Anal. calcd. for C28H25N9O2S2 (583.16):
C 57.62, H 4.32, N 21.60, S 10.99. Found: C 57.45,
H 4.72, N 21.91, S 10.79.
1
1647 (C=O) cm–1; H NMR (DMSO, 300 MHz) δ 2.63 (s,
3H, CH3), 7.48 (s, 2H, H2N), 7.79 (d, 1H, JH-H = 16.8 Hz,
-CH=CH), 7.82–7.89 (m, 5H, H-Ph), 7.98 (d, 1H, JH-H
=
16.8 Hz, -CH=CH), 7.99 (d, 2H, JH-H = 7.2 Hz, H-Ar), 8.04
(d, 2H, JH-H = 7.2 Hz, H-Ar); MS (EI, 70 eV) m/z (%): 369
(M+ +1, 3), 368 (M+, 14). Anal. calcd. for C18H16N4O3S
(368.09): C 58.68, H 4.38, N 15.21, S 8.70. Found: C
58.39, H 4.63, N 15.71, S 8.24.
4-(4-(1-(5-((4-Chlorophenyl)diazenyl)-4-methylthiazol-2-
yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-5-methyl-1H-
1,2,3-triazol-1-yl)benzenesulfonamide (7b) was obtained as
brick red solid (0.73 g, 52%); mp 262–264 °C (EtOH); IR
(KBr) Ʋmax 3439 (NH2) cm–1; 1H NMR (DMSO, 300 MHz)
δ 2.48 (s, 3H, CH3), 2.69 (s, 3H, CH3), 3.47, 3.49 (dd, 1H,
Preparation of 3-(5-methyl-1-(4-sulfamoylphenyl)-1H-1,2,3-
triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioa-
mide (5) To the chalcone 4 (6 g, 16 mmol) and drops of
piperidine in ethanol (40 ml), thiosemicarbazide (1.6 g,
18 mmol) was added. The mixture was refluxed for 6 h, then
left to cool, the solid product was filtered off, washed with
ethanol, and dried.
3-(5-Methyl-1-(4-sulfamoylphenyl)-1H-1,2,3-triazol-4-yl)-
5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (5) was
obtained as white solid (5.4 g, 77%); mp 266–268 °C (EtOH/
DMF); IR (KBr) Ʋmax 3441 (br, NH2), 1358 (C=S) cm–1; 1H
NMR (DMSO, 300 MHz) δ 2.68 (s, 3H, CH3), 3.16, 3.21
(dd, 1H, J = 3.3, JH-H = 18 Hz, CH-pyrazoline), 4.03, 4.09
(dd, 1H, JH-H = 11.4, J = 18 Hz, CH-pyrazoline), 5.94, 5.97
(dd, 1H, JH-H = 3.5, J = 11.6 Hz, CH-Ph), 7.15–7.35 (m, 5H,
H-Ph), 7.71 (s, 2H, NH2-SO2), 7.85 (d, 2H, JH-H = 8.2 Hz, H-
Ar), 8.03 (d, 2H, JH-H = 8.2 Hz, H-Ar), 8.50 (s, 2H, C(S)
NH2); 13C NMR (300 MHz, DMSO): 175.60, 166.22,
161.03, 149.93, 142.66, 128.48, 127.13, 126.95, 125.75,
125.17, 123.57, 119.87, 61.70, 56.21, 10.22; Anal. calcd. for
C19H19N7O2S2 (441.10): C 51.68, H 4.34, N 22.21, S 14.52.
Found: C 51.43, H 4.71, N 22.53, S 14.19.
JH-H = 10.2 Hz, CH-pyrazoline), 4.26, 4.32 (dd, 1H, JH-H
=
10.5 Hz, CH-pyrazoline), 5.86, 5.93 (dd, 1H, CH-Ph),
7.30–7.69 (m, 11H, H-Ph and NH2 and H-(Cl-Ph)), 7.91 (d,
2H, J = 8.1 Hz, H-Ar), 8.09 (d, 2H, J = 8.1 Hz, H-Ar); 13C
NMR (300 MHz, DMSO):164.73, 159.09, 151.21, 150.89,
145.22, 140.68, 140.43, 137.55, 136.89, 134.91, 133.07,
129.20, 128.88, 127.79, 127.21, 125.70, 123.05, 120.61,
61.90, 44.74, 16.02, 10.20; Anal. calcd. for
C28H24ClN9O2S2 (617.12): C 54.41, H 3.91, Cl 5.74, N
20.39, S 10.37. Found: C 54.21, H 3.79, Cl 5.63, N 20.56,
S 10.19.
4-(4-(1-(5-((4-Bromophenyl)diazenyl)-4-methylthiazol-2-
yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-5-methyl-1H-
1,2,3-triazol-1-yl)benzenesulfonamide (7c) was obtained as
brick red solid (0.97 g, 65%); mp 270–272 °C (EtOH); IR
(KBr) Ʋmax 3439 (NH2) cm–1; 1H NMR (DMSO, 300 MHz)
δ 2.49 (s, 3H, CH3), 2.69 (s, 3H, CH3), 3.45–3.49 (dd, 1H,
JH-H = 4.5, JH-H = 18.2 Hz, CH-pyrazoline), 4.19–4.37 (dd,
1H, JH-H = 11.5 Hz, JH-H = 18.0 Hz, CH-pyrazoline),
5.87–5.90 (dd, 1H, JH-H = 4.5, JH-H = 11.5 Hz, CH-Ph),
7.30–7.41(m, 5H, H-Ph), 7.59-7.62 (m, 6H, NH2 + H-(Br-
General procedure for the preparation of 7a–7c and 9a,
9b To a suspension of compound 5 (1 g, 2.26 mmol) in
ethanol (15 ml), the appropriate N-aryl α-keto-hydrazonoyl
halide 6a–6c, 2-bromo-1-phenylethanone 8a, or 2-bromo-1-
(4-bromophenyl)ethanone 8b (2.26 mmol) was added in the
presence of few drops of triethylamine. The reaction mix-
ture was heated under reflux for 1–2 h. The precipitate
formed was collected by suction filtration to afford 7a–7c,
9a, and 9b, respectively.
Ph)), 7.90 (d, 2H, JH-H = 8.4 Hz, H-Ar), 8.10 (d, 2H, JH-H
=
8.4 Hz, H-Ar); 13C NMR (300 MHz, DMSO):164.76,
159.21, 151.27, 145.22, 140.66, 140.44, 137.54, 136.88,
134.93, 132.13, 128.87, 127.79, 127.20, 125.71, 123.33,
121.7, 120.75, 120.70, 61.90, 44.74, 16.05, 10.19; Anal.
calcd. for C28H24BrN9O2S2 (661.07): C 50.76, H 3.65, Br
12.06, N 19.03, S 9.68. Found: C 50.58, H 3.81, Br 11.89,
N 19.20, S 9.77.
4-(5-Methyl-4-(1-(4-methyl-5-(phenyldiazenyl)thiazol-2-
yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-1H-1,2,3-tria-
zol-1-yl)benzenesulfonamide (7a) was obtained as brick red
solid (0.8 g, 61%); mp 256–258 °C (EtOH); IR (KBr) Ʋmax
4-(5-Methyl-4-(5-phenyl-1-(4-phenylthiazol-2-yl)-4,5-
dihydro-1H-pyrazol-3-yl)-1H-1,2,3-triazol-1-yl)benzenesul-
fonamide (9a) was obtained as pale green solid (0.87 g,
70%); mp 178–180 °C (EtOH); 1H NMR (DMSO,
1
3425 and 3325 (NH2) cm–1; H NMR (DMSO, 300 MHz)
300 MHz) δ 2.70 (s, 3H, CH3), 3.41, 3.48 (dd, 1H, JH-H
10.2 Hz, CH-pyrazoline), 4.19, 4.23 (dd, 1H, JH-H
=
=
δ 2.45 (s, 3H, CH3), 2.66 (s, 3H, CH3), 3.42, 3.47 (dd, 1H,
JH-H = 4.6, JH-H = 17.4 Hz, CH-pyrazoline), 4.20, 4.26 (dd,
1H, JH-H = 11.7, JH-H = 17.4 Hz, CH-pyrazoline), 5.84, 5.87
(dd, 1H, JH-H = 4.6, JH-H = 11.7 Hz, CH-Ph), 7.32–7.42
10.5 Hz, CH- pyrazoline), 5.62, 5.79 (dd, 1H, CH-Ph),
7.24–7.46 (m, 10H, 2H-Ph), 7.59 (s, 2H, NH2), 7.71 (s, 1H,
H-thiazole) 7.92 (d, 2H, JH-H = 8.4 Hz, H-Ar), 8.09 (d, 2H,