3.1. Chemistry
All reagents were purchased from Alfa-Aesar and Sigma-Aldrich and used without further purification. Melting points were determined by using Fischer-Johns apparatus (Sanyo, Japan) and are uncorrected. The
1H-NMR spectra were recorded on a Bruker Avance instrument using DMSO-
d6 or CDCl
3 as solvents and tetramethylsilane (TMS) as an internal standard. Chemical shifts are expressed as
δ (ppm). The infrared (IR) spectra were recorded in KBr using a Perkin-Elmer 1725X Fourier transform infrared (FTIR) spectrometer. The purity of the compounds was checked by thin-layer chromatography (TLC) on plates precoated with silica gel Si 60 F
254, produced by Merck Co. (Darmstadt, Germany). The spots were detected by exposure to UV-lamp at λ = 254 nm. Elemental analyses were performed on AMZ 851 CHX analyzer and the results were within ±0.4% of the theoretical value. Molecular properties (
i.e., M
W, TPSA, and logP) of the compounds were calculated using Molinspiration online tool [
30].
3.1.1. General Procedure for the Synthesis of Thiosemicarbazide Derivatives (1–18)
A solution of 0.01 mol of 3-chlorobenzhydrazide or 4-chlorobenzhydrazide and equimolar amount of appropriate aryl isothiocyanate in 25 mL of anhydrous ethanol (EtOH) was heated under reflux for 5 min. Next, the solution was cooled and the solid formed was filtered off, washed with diethyl ether and crystallized from EtOH. Information on already known compounds may be retrieved in the Chemical Abstract Service database (CAS numbers are given below).
1-(3-Chlorobenzoyl)-4-(2-fluorophenyl)thiosemicarbazide (1): Yield: 88%. CAS Registry Number: 894226-73-4.
1-(3-Chlorobenzoyl)-4-(3-fluorophenyl)thiosemicarbazide (2): Yield: 90%. CAS Registry Number: 894226-67-6.
1-(3-Chlorobenzoyl)-4-(4-fluorophenyl)thiosemicarbazide (3): Yield: 85%. CAS Registry Number: 316151-86-7.
1-(3-Chlorobenzoyl)-4-(4-chlorophenyl)thiosemicarbazide (4): Yield: 86%. CAS Registry Number: 351877-21-9.
4-(2-Bromophenyl)-1-(3-chlorobenzoyl)thiosemicarbazide (5): Yield: 86%, CAS Registry Number: 1263379-27-6.
4-(4-Bromophenyl)-1-(3-chlorobenzoyl)thiosemicarbazide (6): Yield: 85%. CAS Registry Number: 351877-22-0.
1-(3-Chlorobenzoyl)-4-(4-iodophenyl)thiosemicarbazide (7): Yield: 96%, CAS Registry Number: 1263379-28-7.
1-(3-Chlorobenzoyl)-4-(2-methylphenyl)thiosemicarbazide (8): Yield: 87%. CAS Registry Number: 891083-31-1.
1-(3-Chlorobenzoyl)-4-(3-methylphenyl)thiosemicarbazide (9): Yield: 86%. CAS Registry Number: 905231-64-3.
1-(3-Chlorobenzoyl)-4-(4-methylphenyl)thiosemicarbazide (10): Yield: 94%. CAS Registry Number: 891082-71-6
4-(4-Acetylphenyl)-1-(3-chlorobenzoyl)thiosemicarbazide (11): Yield: 86%. CAS Registry Number: 891560-05-7
1-(4-Chlorobenzoyl)-4-(2-fluorophenyl)thiosemicarbazide (12): Yield: 93%. CAS Registry Number: 894226-79-0.
1-(4-Chlorobenzoyl)-4-(2,4-difluorophenyl)thiosemicarbazide (13): Yield: 85%. CAS Registry Number: 891552-00-4.
1-(4-Chlorobenzoyl)-4-(2,4-dichlorophenyl)thiosemicarbazide (14): Yield: 90%. CAS Registry Number: 891643-33-7.
4-(2-Bromophenyl)-1-(4-chlorobenzoyl)thiosemicarbazide (15): Yield: 94%, m.p. 174–176 °C, 1H-NMR (300 MHz, DMSO-d6): 7.16–7.23 (m, 2H, Ar-H), 7.40–7.57 (m, 3H, Ar-H), 7.68–7.81 (m, 3H, Ar-H), 9.66 (s, 1H, 1NH, D2O exchangeable), 9.80 (s, 1H, 1NH, D2O exchangeable), 10.65 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3367 (NH), 3110, 2991 (CHarom.), 1652 (C=O), 1296 (C=S). EI-MS (m/z): 383 [M+]. Anal. Calc. for C14H11BrClN3OS (%): C 43.71, H 2.88, N 10.92. Found: C 43.65, H 2.72, N 11.05.
4-(4-Bromophenyl)-1-(4-chlorobenzoyl)thiosemicarbazide (16): Yield: 88%. CAS Registry Number: 356576-31-3.
1-(4-Chlorobenzoyl)-4-[4-(methylsulfanyl)phenyl]thiosemicarbazide (17): Yield: 96%, m.p. 180–182 °C, 1H-NMR (300 MHz, DMSO-d6): 2.26 (s, 3H, SCH3), 7.19 (d, 2H, Ar-H, J = 8.56 Hz), 7.30 (d, 2H, Ar-H, J = 8.55 Hz), 7.38–7.68 (m, 4H, Ar-H), 9.86 (s, 2H, 2NH, D2O exchangeable), 10.74 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3410 (NH), 3076 (CHarom), 2930 (CHaliph.), 1661 (C=O), 1311 (C=S). EI-MS (m/z): 351 [M+]. Anal. Calc. for C15H14ClN3OS2 (%): C 51.20, H 4.01, N 11.94. Found: C 51.03, H 4.11, N 11.98.
1-(4-Chlorobenzoyl)-4-[4-(diethylamino)phenyl]thiosemicarbazide (18): Yield: 87%, m.p. 158–159 °C, 1H-NMR (300 MHz, DMSO-d6): 1.08 (t, 6H, 2CH3, J = 6.80 Hz), 3.10 (q, 4H, 2CH2, J = 6.80 Hz), 6.94 (d, 2H, Ar-H, J = 8.65 Hz), 7.10 (d, 2H, Ar-H, J = 8.65 Hz), 7.45–7.81 (m, 4H, Ar-H), 9.56, 9.68, 10.54 (3s, 3H, 3NH, D2O exchangeable). IR (KBr, cm−1): 3386, 3350 (NH), 3064 (CHarom), 2951, 2863 (CHaliph), 1658 (C=O), 1304 (C=S). Anal. Calc. for C18H21ClN4OS (%): C 57.36, H 5.62, N 14.87. Found: C 57.42, H 5.79, N 14.76.
3.1.2. General Procedure for the Synthesis of 1,2,4-triazole-3-thione Derivatives (1a–18a)
Suitable 1,4-disubstituted thiosemicarbazides (1–18) (0.01 mol) were dissolved in 2% solution of sodium hydroxide and the resulting solution was refluxed for 2 h. After cooling, the mixture was neutralized with 3M hydrochloric acid. The precipitate formed was filtered and washed with distilled water. The compounds were crystallized from EtOH.
5-(3-Chlorophenyl)-4-(2-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (1a): Yield: 81%, m.p. 170–171 °C, 1H-NMR (300 MHz, DMSO-d6): 7.18–7.77 (m, 8H, Ar-H), 14.17 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3453 (NH), 3012 (CHarom), 1485 (C=N), 1321 (C=S). EI-MS (m/z): 305 [M+]. Anal. Calc. for C14H9ClFN3S (%): C 54.99, H 2.97, N 13.74. Found: C 55.06, H 2.76, N 13.88.
5-(3-Chlorophenyl)-4-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (2a): Yield: 83%, m.p. 221–222 °C, 1H-NMR (300 MHz, DMSO-d6): 7.17–7.62 (m, 8H, Ar-H), 14.27 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3461 (NH), 3002 (CHarom.), 1483 (C=N), 1320 (C=S). EI-MS (m/z): 305 [M+]. Anal. Calc. for C14H9ClFN3S (%): C 54.99, H 2.97, N 13.74. Found: C 55.08, H 2.81, N 13.85.
5-(3-Chlorophenyl)-4-(4-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (3a): Yield: 90%. CAS Registry Number: 720667-75-4.
4-(4-Chlorophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4a): Yield: 82%. CAS Registry Number: 879074-80-3.
4-(2-Bromophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (5a): Yield: 85%. CAS Registry Number: 1263379-33-4.
4-(4-Bromophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (6a): Yield: 95%. CAS Registry Number: 1263379-32-3.
5-(3-Chlorophenyl)-4-(4-iodophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (7a): Yield: 87%. CAS Registry Number: 1263379-34-5.
5-(3-Chlorophenyl)-4-(2-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8a): Yield: 87%, m.p. 186–188 °C, 1H-NMR (300 MHz, DMSO-d6): 2.13 (s, 3H, CH3), 7.12–7.86 (m, 8H, Ar-H), 14.17 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3387 (NH), 3046 (CHarom.), 2931 (CHaliph), 1494 (C=N), 1332 (C=S). EI-MS (m/z): 301 [M+]. Anal. Calc. for C15H12ClN3S (%):C 59.70, H 4.01, N 13.92. Found: C 59.79, H 3.87, N 14.03.
5-(3-Chlorophenyl)-4-(3-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (9a): Yield: 83%, m.p. 200–201 °C, 1H-NMR (300 MHz, DMSO-d6): 2.32 (s, 3H, CH3), 7.10–7.53 (m, 8H, Ar-H), 14.09 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3415 (NH), 3068 (CHarom.), 2864 (CHaliph.), 1476 (C=N), 1322 (C=S). EI-MS (m/z): 301 [M+]. Anal. Calc. for C15H12ClN3S (%):C 59.70, H 4.01, N 13.92. Found: C 59.81, H 4.09, N 14.13.
5-(3-Chlorophenyl)-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (10a): Yield: 80%. CAS Registry Number: 893725-08-1.
4-(4-Acetylphenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (11a): Yield: 84%, m.p. 218–220 °C, 1H-NMR (300 MHz, DMSO-d6): 2.64 (s, 3H, CH3), 7.21–8.14 (m, 8H, Ar-H), 14.27 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3421 (NH), 3041 (CHarom.), 2924 (CHalif.), 1666 (C=O), 1490 (C=N), 1328 (C=S). Anal. Calc. for C16H12ClN3OS (%): C 58.27, H 3.67, N 12.74. Found: C 58.14, H 3.58, N 12.67.
5-(4-Chlorophenyl)-4-(2-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (12a): Yield: 86%, m.p. 240–242 °C, 1H-NMR (300 MHz, DMSO-d6): 7.40 (d, 2H, Ar-H, J = 8.70 Hz), 7.52 (d, 2H, Ar-H, J = 8.69 Hz), 7.58–7.86 (m, 4H, Ar-H), 14.32 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3387 (NH), 3034 (CHarom.), 1489 (C=N), 1328 (C=S). Anal. Calc. for C14H9ClFN3S (%): C 54.99, H 2.97, N 13.74. Found: C 55.10, H 3.00, N 13.61.
5-(4-Chlorophenyl)-4-(2,4-difluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (13a): Yield: 86%, m.p. 196–198 °C, 1H-NMR (300 MHz, DMSO-d6): 7.24 (d, 2H, Ar-H, J = 8.63 Hz), 7.42 (d, 2H, Ar-H, J = 8.61 Hz), 7.58–7.81 (m, 3H, Ar-H), 14.29 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3420 (NH), 3100 (CHarom.), 1483 (C=N), 1336 (C=S). EI-MS (m/z): 323 [M+]. Anal. Calc. for C14H8ClF2N3S (%): C 51.94, H 2.49, N 12.98. Found: C 52.13, H 2.50, N 12.81.
5-(4-Chlorophenyl)-4-(2,4-dichlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (14a): Yield: 88%, m.p. 238–240 °C, 1H-NMR (300 MHz, DMSO-d6): 7.39 (d, 2H, Ar-H, J = 8.65 Hz), 7.55 (d, 2H, Ar-H, J = 8.66 Hz), 7.70–7.95 (m, 3H, Ar-H), 14.39 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3387 (NH), 3049 (CHarom.), 1490 (C=N), 1318 (C=S). Anal. Calc. for C14H8Cl3N3S (%): C 47.15, H 2.26, N 11.78. Found: C 47.13, H 2.30, N 11.66.
4-(2-Bromophenyl)-5-(4-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (15a): Yield: 90%, m.p. 250–252 °C, 1H-NMR (300 MHz, DMSO-d6): 7.36 (d, 2H, Ar-H, J = 8.61 Hz), 7.50 (d, 2H, Ar-H, J = 8.61 Hz), 7.67–7.91 (m, 4H, Ar-H), 14.30 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3401 (NH), 3105 (CHarom), 1496 (C=N), 1342 (C=S). EI-MS (m/z): 365 [M+]. Anal. Calc. for C14H9BrClN3S (%): C 45.86, H 2.47, N 11.46. Found: C 45.65, H 2.53, N 11.60.
4-(4-Bromophenyl)-5-(4-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (16a): Yield: 84%, CAS Registry Number: 537017-82-6.
5-(4-Chlorophenyl)-4-[4-(methylsulfanyl)phenyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (17a): Yield: 88%, m.p. 214–216 °C, 1H-NMR (300 MHz, DMSO-d6): 2.42 (s, 3H, CH3), 7.23–7.85 (m, 8H, Ar-H), 14.29 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3412 (NH), 3075 (CHarom), 2886 (CHaliph.), 1568 (C=N), 1320 (C=S). EI-MS (m/z): 333 [M+]. Anal. Calc. for C15H12ClN3S2 (%): C 53.96, H 3.62, N 12.59. Found: C 54.10, H 3.54, N 13.02.
5-(4-Chlorophenyl)-4-[4-(diethylamino)phenyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (18a): Yield: 80%, m.p. 264–266 °C, 1H-NMR (300 MHz, DMSO-d6): 1.10 (t, 6H, 2 × CH3, J = 7.08 Hz), 3.34 (q, 4H, 2CH2, J = 7.10 Hz), 7.10 (d, 2H, Ar-H, J = 8.80 Hz), 7.21 (d, 2H, Ar-H, J = 8.80 Hz), 7.28–7.61 (m, 4H, Ar-H), 14.23 (s, 1H, NH, D2O exchangeable). IR (KBr, cm−1): 3422 (NH), 3041 (CHarom.), 2926, 2864 (CHaliph.), 1559 (C=N), 1330 (C=S). Anal. Calc. for C18H19ClN4S (%): C 60.24, H 5.34, N 15.61. Found: C 60.31, H 5.48, N 15.60.
3.1.3. General Procedure for the Synthesis of Mannich Bases (19a–30a)
Ten mmol of the 1,2,4-triazole derivative (
6a,
10a,
15a,
16a) was dissolved (with heating) in 20 mL of anhydrous ethanol and then equimolar amounts of appropriate secondary amine (morpholine, 1-phenylpiperazine, 1-[4-fluorophenyl]piperazine) and formaldehyde solution (37%) were added. The obtained mixture was stirred at room temperature for 1 h. Next, 5 mL of distilled water was added, the precipitate was filtered off, washed with distilled water, and crystallized from ethanol. Spectral and physicochemical data for compounds
19a–
24a, and
28a are available in our earlier articles [
31,
32].
4-(4-Bromophenyl)-5-(3-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2, 4-triazole-3-thione (19a): Yield: 75%. CAS Registry Number: 1349172-90-2.
4-(4-Bromophenyl)-5-(3-chlorophenyl)-2-[(4-phenylpiperazin-1-yl)methyl]-2,4-dihydro-3H-1,2, 4-triazole-3-thione (20a): Yield: 78%. CAS Registry Number: 1349172-92-4.
4-(4-Bromophenyl)-5-(3-chlorophenyl)-2-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-2, 4-dihydro-3H-1,2,4-triazole-3-thione (21a): Yield: 82%. CAS Registry Number: 1349172-94-6.
5-(3-Chlorophenyl)-4-(4-methylphenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2, 4-triazole-3-thione (22a): Yield: 72%. CAS Registry Number: 1349172-89-9.
5-(3-Chlorophenyl)-4-(4-methylphenyl)-2-[(4-phenylpiperazin-1-yl)methyl]-2,4-dihydro-3H-1,2, 4-triazole-3-thione (23a): Yield: 79%. CAS Registry Number: 1349172-91-3.
5-(3-Chlorophenyl)-2-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-4-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (24a): Yield: 83%. CAS Registry Number: 1349172-93-5.
4-(2-Bromophenyl)-5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (25a): Yield: 80%, m.p. 180–181 °C, 1H-NMR (300 MHz, CDCl3): 2.93 (t, 4H, morpholine, J = 4.70 Hz), 3.75 (t, 4H, morpholine, J = 4.70 Hz), 5.25 (s, 2H, CH2), 7.20 (d, 2H, Ar-H, J = 8.60 Hz), 7.26–7.34 (m, 4H, Ar-H), 7.65 (d, 2H, Ar-H, J = 8.60 Hz). 13C-NMR (75 MHz, CDCl3): 50.86, 66.90, 70.05, 123.49, 124.20, 129.23, 129.43, 129.53, 129.77, 129.89, 133.14, 133.85, 137.21, 148.21, 170.61. EI-MS (m/z): 464 [M+]. Anal. Calc. for C19H18BrClN4OS (%): C 48.99, H 3.90, N 12.03. Found: C 49.12, H 3.78, N 12.00.
4-(2-Bromophenyl)-5-(4-chlorophenyl)-2-[(4-phenylpiperazin-1-yl)methyl]-2,4-dihydro-3H-1,2, 4-triazole-3-thione (26a): Yield: 73%, m.p. 140–142 °C, 1H-NMR (600 MHz, CDCl3): 3.09–3.20 (m, 4H, piperazine), 3.27 (t, 4H, piperazine, J = 4.9 Hz), 5.31 (d, 1H, CH2, J = 13.2 Hz), 5.48 (d, 1H, CH2, J = 13.2 Hz), 6.89 (t, 1H, Ar-H, J = 7.2 Hz), 6.97 (d, 2H, Ar-H, J = 7.4 Hz), 7.27–7.32 (m, 5H, Ar-H), 7.34 (dd, 2H, Ar-H, J = 1.9 Hz, 5.9 Hz), 7.42–7.48 (m, 2H, Ar-H), 7.55 (td, 1H, Ar-H, J = 1.2 Hz, 7.6 Hz), 7.75 (dd, 1H, Ar-H, J = 1.2 Hz, 7.9 Hz). 13C NMR (150 MHz, CDCl3): 49.48, 50.40, 69.63, 116.41, 123.35, 123.87, 129.07, 129.16, 129.19, 130.92, 131.91, 134.20, 134.40, 137.12, 148.20, 170.43. IR (KBr, cm−1): 3084, 3006 (CHarom), 2892, 2784 (CHaliph), 1495 (C=N), 1314 (C=S). Anal. Calc. for C25H23BrClN5S (%):C 55.51, H 4.29, N 12.95. Found: C 55.57, H 4.12, N 12.79.
4-(2-Bromophenyl)-5-(4-chlorophenyl)-2-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-2, 4-dihydro-3H-1,2,4-triazole-3-thione (27a): Yield: 82%, m.p. 168–170 °C, 1H-NMR (600 MHz, CDCl3): 3.09–3.25 (m, 8H, piperazine), 5.30 (d, 1H, CH2, J = 13.4 Hz), 5.47 (d, 1H, CH2, J = 13.4 Hz), 6.89-6.96 (m, 2H, Ar-H), 6.99 (t, 2H, Ar-H, J = 8.1 Hz), 7.27–7.36 (m, 4H, Ar-H), 7.42–7.47 (m, 2H, Ar-H), 7.55 (td, 1H, Ar-H, J = 1.3 Hz, 7.6 Hz), 7.75 (dd, 1H, Ar-H, J = 1.3 Hz, 8.0 Hz). 13C NMR (150 MHz, CDCl3): 50.32, 50.54, 69.51, 115.57, 115.72, 123.34, 123.83, 129.06, 129.16, 130.90, 131.92, 134.20, 134.38, 137.16, 148.23, 170.44. IR (KBr, cm−1): 3130, 3085 (CHarom.), 2956, 2879 (CHaliph.), 1486 (C=N), 1317 (C=S). Anal. Calc. for C25H22BrClFN5S (%): C 53.73, H 3.97, N 12.53. Found: C 53.80, H 3.76, N 12.69.
4-(4-Bromophenyl)-5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (28a): Yield: 69%. CAS Registry Number: 1403137-49-4.
4-(4-Bromophenyl)-5-(4-chlorophenyl)-2-[(4-phenylpiperazin-1-yl)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (29a): Yield: 78%, m.p. 178–180 °C, 1H-NMR (CDCl3): 3.12–3.15 (m, 4H, piperazine), 3.25–3.28 (m, 4H, piperazine), 5.37 (s, 2H, CH2), 6.90 (t, 1H, Ar-H, J = 7.30 Hz), 6.96 (d, 2H, Ar-H, J = 8.20 Hz), 7.21 (d, 2H, Ar-H, J = 8.60 Hz), 7.25–7.39 (m, 6H, Ar-H), 7.69 (d, 2H, Ar-H, J = 8.60 Hz). 13C NMR (CDCl3): 49.50, 50.60, 69.89, 116.51, 120.16, 123.56, 124.23, 129.23, 129.28, 129.61, 129.95, 133.19, 133.92, 137.20, 148.20, 151.31, 170.60. EI-MS (m/z): 539 [M+]. Anal. Calc. for C25H23BrClN5S (%): C 55.51, H 4.29, N 12.95. Found: C 55.38, H 4.38, N 13.12.
4-(4-Bromophenyl)-5-(4-chlorophenyl)-2-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-2, 4-dihydro-3H-1,2,4-triazole-3-thione (30a): Yield: 80%, m.p. 156–158 °C, 1H-NMR (CDCl3): 3.07–3.20 (m, 8H, piperazine), 5.35 (s, 2H, CH2), 6.87–7.02 (m, 4H, Ar-H), 7.19 (d, 2H, Ar-H, J = 8.40 Hz), 7.24–7.32 (m, 4H, Ar-H), 7.66 (d, 2H, Ar-H, J = 8.40 Hz). 13C NMR (CDCl3): 50.50, 50.55, 69.78, 115.47, 115.77, 118.25, 118.35, 123.49, 124.24, 129.25, 129.54, 129.88, 133.18, 133.86, 137.23, 147.90, 148.20, 170.57. EI-MS (m/z): 557 [M+]. Anal. Calc. for C25H22BrClFN5S (%): C 53.73, H 3.97, N 12.53. Found: C 53.87, H 4.11, N 12.45.