Molecules 2009, 14
2628
(39.5%), 516.11 (477+39) (13%), 977 (477×2+23) (30%). Anal. calcd. for C24H23N5O4S (%): C,
60.37; H, 4.82; N, 14.67; S, 6.70; found: C, 60.81; H, 5.01; N, 15.10; S, 7.19.
3.1.5. General procedure for synthesis of 1,3,4-thiadiazoles 6, 7
To the corresponding thiosemicarbazide 4, 5 (0.006 mol), concentrated H2SO4 (1 mL) was added
under stirring. The reaction mixture was stirred at room temperature for one hour and then was added
dropwise in cold water and stirred again till a solid product was obtained that was separated and dried
under vacuum at 45-50ºC. The rough product was purified by crystallization from ethanol.
2-[1-(p-Nitrobenzoylamino)-2-phenyl]-ethyl-5-(p-bromophenylamino)-1,3,4-thiadiazole (6): light
yellow solid, 223 mg (71.50% yield), mp 151-153°C; IR (cm-1) ν: 3,263, 3,066 (NH), 1,672 (C=N),
1,620 (CO), 1,520 (asymmetric NO2 vibrations), 1,341 (symmetric NO2 vibrations), 812 (aromatic
1
CH), 750 (C-Br), 640 (C-S); H-NMR (DMSO-d6, 300 MHz) δ: 2.60 – 2.65 (m, 2 H, CH2), 4.76 (m,
1H, NH), 6.00 (m, 1H, CH), 6.56 (d, 2H, ArCH), 7.63 – 7.78 (m, 5H, ArCH), 8.30 (d, 2H, ArCH), 8.40
(d, 2H, ArCH), 8.80 (d, 2H, ArCH), 9.10 (s, 1H, -NH-CO-); MS (acetonitrile/water 95/5, v/v) m/z: 524
(base peak), 1047 (1.5%); Anal. calcd. for C23H18N5O3BrS (%): C, 52.67; H, 3.43; N, 13.35; Br, 15.26;
S, 6.10; found: C, 53.02; H, 3.89; N, 13.84; Br, 15.67; S, 6.58.
2-[1-(p-Nitrobenzoylamino)-2-phenyl]-ethyl-5-(p-tolylamino)-1,3,4-thiadiazole (7): yellow solid, 195
mg (71.27% yield), mp 180-182°C; IR (cm-1) ν: 3,259, 3,192 (NH), 1,665 (C=N), 1,620 (CO), 1,552
1
(asymmetric NO2 vibrations), 1,384 (symmetric NO2 vibrations), 815 (aromatic CH), 652 (C-S); H-
NMR (DMSO-d6, 300 MHz) δ: 2.34 (s, 3H, CH3), 2.60 – 2.63 (m, 2H, CH2), 4.76 (m, 1H, NH), 6.05
(m, 1H, CH), 6.58 (d, 2H, ArCH), 7.63-7.80 (m, 5H, ArCH), 8.33 (d, 2H, ArCH), 8.45 (d, 2H, ArCH),
8.75 (d, 2H, ArCH), 9.08 (s, 1H, -NH-CO-); MS (acetonitrile/water 95/5, v/v) m/z: 460.13 (base peak),
482.02 (1%), 919.14 (2%), 941.12 (1%); Anal. calcd. for C24H21N5O3S (%): C, 62.74; H, 4.57; N,
15.25; S, 6.97; found: C, 63.22; H, 4.91; N, 15.70; S, 7.47.
3.1.6. General procedure for the synthesis of 1,2,4-triazoles 8, 9
To corresponding thiosemicarbazide 6, 7 (0.0014 mol), a solution of NaOH 2N (10 mL) was added.
The reaction mixture was heated under reflux at 80-90 °C for four hours and then a solution of HCl 1N
was added until it reached pH 4.5 when a solid product was formed. The rough product was separated
and dried under vacuum at 55-60ºC and then it was recrystallized from ethanol.
4-(p-bromophenyl)-5-[1-(p-nitrobenzoylamino)-2-phenyl-ethyl]-3-thio-1,2,4-triazole (8): yellow-
orange solid, 46 mg (64.45% yield), mp 147-149°C; IR (cm-1) ν: 3,062 (NH), 1,664 (CO), 1,595
(C=N), 1,546 (asymmetric NO2 vibrations), 1,300 (C=S), 1,332 (symmetric NO2 vibrations), 925, 873
(aromatic CH), 752 (C-Br); 1H-NMR (DMSO-d6, 300 MHz) δ: 2.62 – 2.66 (m, 2H, CH2), 4.86 (m, 1H,
CH), 7.25 – 7.30 (m, 5H, ArCH), 7.80 (d, 2H, ArCH), 8.39 ( d, 2H, ArCH), 8.50 (d, 2H, ArCH), 8.75
(d, 2H, ArCH), 9.05 (m, 1H, -NH-CO-), 12.80 (s, 1H, NH); MS (acetonitrile/water 95/5, v/v) m/z:
524.03 (base peak), 541.94 (33%), 563.92 (25%), 1069.01 (9%); Anal. calcd. for C23H18N5O3BrS (%):
C, 52.67; H, 3.43; N, 13.35; Br, 15.26; S, 6.10; found: C, 53.08; H, 3.85; N, 13.85; Br, 15.26; S, 6.49.