4-(4-CHLOROPHENYL)-5-(4-METHYLPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL synthesis

Yield:713128-34-8 23.5%

Reaction Conditions:

with potassium carbonate in acetone at 20; for 14 h;

Steps:

5.1.1 Preparation of 2-(4-(4-chlorophenyl)-5-p-tolyl-4H-1,2,4-triazol-3-ylthio)-1-(3,4-dihydroxyphenyl)ethanone (4, XDW-1)

To a solution of the 4-(4-chlorophenyl)-5-p-tolyl-4H-1,2,4-triazole-3-thiol (3) (CAS No. 451501-95-4) (0.6g, 1.99mmol) in acetone (30mL) was added K₂CO₃ (0.3g, 2.17mmol) followed by 2-chloro-1-(3,4-dihydroxyphenyl)ethanone (2) (0.35g, 1.88mmol). The resulting solution was stirred at room temperature for 14h, diluted with water and extracted with EtOAc. The organic layer waswashed with water, dried on anhydrous Na₂SO₄, then filtered and evaporated under reduced pressure to afford white solid as crude product. Then recrystallization of the crude product in ethanol/ petroleum(60-90) gave the purified product 2-(4-(4-chlorophenyl)-5-p-tolyl-4H-1,2,4-triazol-3-ylthio)-1-(3,4-dihydroxyphenyl)ethanone (XDW-1, 4) as white solid. Yield: 0.20g, 23.5%; R_f=0.50 (petroleum 60-90/EtOAc, 1:1). ¹H NMR (400MHz, DMSO-d6, ppm) δ: 9.71 (2H, brs, 2×OH), 7.62 (2H, d, J=8.6Hz), 7.46 (2H, d, J=8.7Hz), 7.44 (1H, dd, J=8.7, 2.4Hz), 7.36 (1H, d, J=2.4Hz), 7.23 (2H, d, J=8.2Hz), 7.17 (2H, d, J=8.2Hz), 6.84 (1H, d, J=8.2Hz), 4.80 (2H, s, S-CH₂), 2.28 (3H, s, Me). ESI-MS: m/z 452.3 (M+1), 454.4 (M+3). C₂₃H₁₈ClN₃O₃S (451.076).

References:

Song, Yu'Ning;Lin, Xiaoqian;Kang, Dongwei;Li, Xiao;Zhan, Peng;Liu, Xinyong;Zhang, Qingzhu [European Journal of Medicinal Chemistry,2014,vol. 82,p. 293 - 307]