S.A. Shahzad et al.
BioorganicChemistry85(2019)209–220
reaction mixture was acidified using dilute hydrochloric acid (adjusted
pH 6). Resulting precipitates were filtered, washed with water and re-
crystallized from aqueous ethanol. The resulting substituted-1,2,4-
triazole carboxylic acids 4a–4g were collected and recrystallized from
ethanol.
4.5.3.8. 5-(3,4,5-Trimethoxyphenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-
triazole-3-thione (3h). Yield: 71%. IR (cm−1, KBr): 1560, 1613, 2582,
3064, 3372; 1H NMR (400 MHz, DMSO‑d6): δ 3.52 (s, 6H, 3,5-(OCH3)2),
3.62 (s, 3H, OCH3), 6.57 (s, 2H, Ar-H), 7.36–7.38 (m, 2H, Ar-H),
7.51–7.55 (m, 3H, Ar-H), 14.09 (s, 1H, NH) ppm. EI MS: m/z (rel
abund. %): 343 (M+, 54), 342 (16), 329 (4), 328 (10), 193 (15), 285
(2), 150 (32), 149 (13), 135 (22), 120 (21), 118 (14), 104 (7), 91 (18),
77 (1 0 0), 65 (21), 51 (37). HRESI-MS: m/z calcd for C17H17N3O3S
(M + H+): 344.1001; found: 344.1011.
4.5.3.1. 5-Phenyl-4H-1,2,4-triazole-3-thiol (3a). Yield: 93%, white
solid; m.p. 255–256 °C. IR (cm−1, KBr): 1485, 1571, 1612, 2598,
3007, 3355; 1H NMR (400 MHz, DMSO‑d6): δ 7.52–7.53 (m, 3H, Ar-
H), 7.91–7.93 (m, 2H, Ar-H), 13.68 (1H, s, NH) and 13.86 ppm (1H, s,
NH). 13C NMR (100 MHz, DMSO‑d6): δ 126.1, 126.2, 129.5, 131.0
(aromatic carbons), 150.9 (C-5), 167.5 (C-3). HRESI-MS: m/z calcd for
C8H7N3S (M + H+): 178.0439; found: 178.0450.
4.5.3.9. 5-(3-Chlorophenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-
thione (3i). Yield: 76%. IR (cm−1, KBr): 1551, 1607, 2558, 3051, 3365;
1H NMR (400 MHz, DMSO‑d6): δ 7.22–7.25 (m, 1H, Ar-H), 7.30–7.32
(m, 2H, Ar-H), 7.35–7.38 (m, 2H, Ar-H), 7.45–7.51 (m, 4H, Ar-H),
14.24 (s, 1H, NH) ppm. EIMS (m/z, rel. abund.%): 287 (M+, 100), 289
(M++2, 37), 288 (50), 286 (92), 256 (2), 254 (3), 228 (7), 137 (5), 135
(7), 91 (6), 77 (18), 65 (3), 51 (8). HRESI-MS: m/z calcd for
C14H10ClN3S (M + H+): 288.0333; found: 288.0340.
4.5.3.2. 5-(3-chlorophenyl)-4H-1,2,4-triazole-3-thiol (3b). 1H NMR
(400 MHz, DMSO‑d6) δ: 7.50–7.57 (m, 2H, Ar-H), 7.83–7.87 (m, 1H,
Ar-H); 7.93 (s, 1H, Ar-H); 13.77 (bs, 1H, NH) ppm (1H, s). 13C NMR
(400 MHz, DMSO‑d6) δ: 111.6, 117.9, 126.8, 130.4, 133.6, 146.7,
152.3. HRESI-MS: m/z calcd for C8H6N3SCl (M + H+): 212.0091;
found: 212.0128.
4.5.3.10. 5-(4-Chlorophenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-
thione (3j). Yield: 79%. IR (cm−1, KBr): 1553, 1608, 2557, 3054, 3366;
1H NMR (400 MHz, DMSO‑d6): δ 7.29 (d, 2H, J = 6.8 Hz, Ar-H),
7.34–7.36 (m, 2H, Ar-H), 7.41 (d, 2H, J = 6.8 Hz, Ar-H), 7.48–7.50
(m, 3H, Ar-H), 14.17 (s, 1H, NH) ppm. EIMS (m/z, rel. abund.%): 287
(M+, 100), 289 (M++2, 35), 288 (49), 286 (93), 256 (4), 254 (6), 228
(9), 137 (7), 135 (11), 91 (8), 77 (17), 65 (5), 51 (13). HRESI-MS: m/z
calcd for C14H10ClN3S (M + H+): 288.0333; found: 288.0339.
4.5.3.3. 5-(4-Chlorophenyl)-4H-1,2,4-triazole-3-thiol (3c). Yield: 88%,
white solid; m.p. 284–287 °C, IR (cm−1, KBr): 1510, 1565, 1610,
2581, 3061, 3431; 1H NMR (400 MHz, DMSO): 7.55 (d, 2H, Ar-H),
7.90 (d, 2H, Ar-H), 13.71 (1H, s, NH), 13.89 (1H, s, NH). 13C NMR
(100 MHz, DMSO): δ 125.3, 127.8, 129.6, 135.5, 150.4 (C-5), 167.8 (C-
3). HRESI-MS: m/z calcd for C8H6N3SCl (M + H+): 212.0081; found:
212.0136.
4.5.3.11. 5-(3-Pyridyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione
(3k). Yield: 70%. IR (cm−1, KBr): 1548, 1615, 2533, 3044, 3321; 1H
NMR (400 MHz, DMSO‑d6): δ 7.36–7.40 (m, 3H, Ar-H), 7.48–7.51 (m,
3H, Ar-H), 7.64–7.67 (m, 1H, Ar-H), 8.48–8.58 (m, 2H, Ar-H), 14.22 (s,
1H, NH) ppm. EIMS (m/z, rel. abund.%): 254 (M+, 100), 253 (68), 221
(3), 195 (9), 194 (6), 150 (4), 149 (13), 119 (17), 118 (4), 104 (13), 92
(11), 91 (11), 78 (20), 77 (54), 65 (13), 52 (5), 51 (36). HRESI-MS: m/z
calcd for C13H10N4S (M + H+): 255.0613; found: 255.0618.
4.5.3.4. 5-(4-Methylphenyl)-4H-1,2,4-triazole-3-thiol (3d). Yield: 86%,
white solid; m.p. 263–265 °C, IR (cm−1, KBr): 1485, 1525, 1566,
1616, 2593, 2915, 3019, 3345; 1H NMR (400 MHz, DMSO‑d6): δ 2.39
(s, 3H, Ar-CH3) 7.29 (d, 2H, J = 8.1 Hz, Ar-H), 7.80 (d, 2H, J = 8.1 Hz,
Ar-H), 13.63(s, 1H, NH) and 13.77 (s, 1H, NH). 13C NMR (100 MHz,
DMSO‑d6): δ 21.4 (CH3) 124.3, 126.0, 130.0, 140.4, 152.1 (C-5), 167.5
(C-3). HRESI-MS: m/z calcd for C9H9N3S (M + H+): 192.0592; found:
192.0614.
4.5.3.12. 5-(4-Pyridyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione
(3l). Yield: 73%. IR (cm−1, KBr): 1550, 1618, 2537, 3049, 3331; 1H
NMR (400 MHz, DMSO‑d6): δ 7.44 (m, 4H, Ar-H), 7.53–7.55 (m, 4H, Ar-
H), 8.70 (m, 1H, Ar-H), 14.50 (s, 1H, NH) ppm. EIMS (m/z, rel. abund.
%): 254 (M+, 100), 253 (81), 221 (2), 195 (10), 194 (5), 150 (5), 149
(15), 119 (11), 118 (6), 104 (9), 92 (6), 91 (12), 78 (18), 77 (51), 65
(12), 52 (6), 51 (51). HRESI-MS: m/z calcd for C13H10N4S (M + H+):
255.0613; found: 255.0619.
4.5.3.5. 5-(4-Nitrophenyl)- 4H-1,2,4-triazole-3-thiol (3e). Yield: 68%,
brown-yellow solid; m.p. > 319 °C (lit. [44] m.p. > 320 °C). IR
(cm−1
,
KBr): 1519, 1567, 1612, 2589, 3060, 3381; 1H NMR
(400 MHz, DMSO‑d6): 8.15 (d, 2H, J = 7.9 Hz, Ar-H), 8.30 (d, 2H,
J = 7.9 Hz, Ar-H), 13.53 (s, 1H, NH); 13C NMR (100 MHz, DMSO): δ
124.1, 126.2, 129.1, 136.2, 151.2 (C-5), 167.1 (C-3). HRESI-MS: m/z
calcd for C8H6N4O2S (M + H+): 223.0292; found: 223.0314.
4.5.3.6. 4,5-Diphenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (3f). Yield:
83%. IR (cm−1, KBr): 1555, 1618, 2575, 3071, 3368; 1H NMR
(400 MHz, DMSO‑d6): δ 7.27–7.31 (m, 3H, Ar-H), 7.33–7.35 (m, 3H,
Ar-H), 7.38–7.42 (m, 1H, Ar-H), 7.47–7.50 (m, 3H, Ar-H), 14.09 (1H, s,
NH) ppm. EI MS: m/z (rel abund. %): 253 (M+, 52), 252 (39), 194 (9),
193 (3), 150 (11), 149 (16), 118 (22), 103 (44), 104 (14), 91 (35), 77
(1 0 0), 65 (18), 64 (17), 63 (17), 51 (70). HRESI-MS: m/z calcd for
4.5.3.13. 2-[(5-phenyl-4H-1,2,4-triazol-3-yl)thio]acetic acid (4a). Yield:
90%. IR (cm−1, KBr): 3300–2325 (COOH), 1704 (C]O); 1H NMR
(400 MHz, DMSO‑d6): δ 4.01 (s, 2H, CH2), 7.51–7.54 (m, 3H, Ar-H),
7.97–7.99 (m, 2H, Ar-H), 13.91 (s, 1H, NH), 15.88 (s, 1H, COOH) ppm.
HRESI-MS: m/z calcd for C10H9N3O2S [M−H]− 234.0468; Found
234.0471.
C
14H11N3S (M + H+): 254.0739; found: 254.0750.
4.5.3.14. 2-[(5-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl)thio]acetic
acid
(4b). Yield: 87%. IR (cm−1, KBr): 3300–2310 (COOH), 1743 (C]O);
1H NMR (400 MHz, DMSO‑d6): δ 4.11 (s, 2H, CH2), 7.55–7.68 (m, 2H,
Ar-H), 7.98–8.02 (m, 1H, Ar-H); 8.06 (s, 1H, Ar-H) 13.91 (s, 1H, NH),
15.88 (s, 1H, COOH) ppm. HRESI-MS: m/z calcd for C10H8N3O2S
[M−H]− 268.0068; Found 268.0272.
4.5.3.7. 5-(4-Methylphenyl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-
thione (3g). Yield: 81%. IR (cm−1, KBr): 1557, 1607, 2572, 3073,
3378; 1H NMR (400 MHz, DMSO‑d6): δ 7.11–7.18 (m, 4H, Ar-H),
7.30–7.33 (m, 2H, Ar-H), 7.46–7.49 (m, 3H, Ar-H), 14.05 (s, 1H, NH)
ppm. EIMS (m/z, rel. abund. %): 267 (M+, 100), 266 (78), 208 (11),
194 (7), 150 (7), 149 (19), 132 (16), 131 (15), 118 (17), 117 (22), 109
(8), 91 (37), 77 (68), 65 (22), 51 (24). HRESI-MS: m/z calcd for
4.5.3.15. 2-[(5-(3-chlorophenyl)-4H-1,2,4-triazol-3-yl)thio]propanoic
acid (4c). Yield: 78%. IR (cm−1, KBr): 3300–2340 (COOH), 1742 (C]
O); 1H NMR (400 MHz, DMSO‑d6): δ 1.55 (d, 3H, CH3), 4.19 (q, 1H,
C
15H13N3S (M + H+): 268.0845.1001; found: 268.0849.
218