W. Zhou, C. Xu, G. Dong et al.
European Journal of Medicinal Chemistry 217 (2021) 113326
4.5.7. 2-(5-mercapto-4H-1,2,4-triazol-3-yl)phenol (5g)
4.5.16. 5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol (5p)
White solid, yield: 74%, m.p.: 275e276 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
11.76 (s, 2H), 7.92 (d, J ¼ 8.5 Hz, 2H), 7.56 (d, J ¼ 8.3 Hz,
White solid, yield: 55%, m.p.: 255e257 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d
7.69e7.65 (m,1H), 7.33e7.28 (m,1H), 6.96 (d, J ¼ 8.2 Hz,
d
1H), 6.90 (t, J ¼ 7.4 Hz, 1H). 13C NMR (100 MHz, DMSO‑d6)
d
166.3,
2H). 13C NMR (100 MHz, DMSO‑d6)
d 167.5, 150.7, 134.7, 129.0, 127.3,
155.8, 131.5, 127.7, 119.2, 116.5, 112.5. HR-MS(ESI): Calcd. C9H9N3OS,
125.6. HR-MS(ESI): Calcd. C8H6ClN3S, [MþH]þm/z: 212.0044,
[MþH]þm/z: 194.0383, found: 194.0385.
found: 212.0043.
4.5.8. 5-(2-aminophenyl)-4H-1,2,4-triazole-3-thiol (5h)
4.5.17. 5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol (5q)
White solid, yield: 50%, m.p.: 260e262 ꢁC. 1H NMR (400 MHz,
White solid, yield: 67%, m.p.: 253e255 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d
13.67 (s, 1H), 7.68 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.21e7.12 (m,
DMSO‑d6)
d
13.69 (s, 1H), 13.55 (s, 1H), 7.85 (d, J ¼ 8.9 Hz, 2H), 7.07
1H), 6.82 (d, J ¼ 8.2 Hz, 1H), 6.65e6.56 (m, 1H). 13C NMR (100 MHz,
(d, J ¼ 8.9 Hz, 2H), 3.82 (s, 3H). 13C NMR (100 MHz, DMSO‑d6)
DMSO‑d6)
d
165.8, 151.0, 146.8, 130.9, 127.1, 116.0, 115.3, 106.0. HR-
d 166.6, 160.9, 150.1, 127.3, 117.8, 114.5, 55.3. HR-MS(ESI): Calcd.
MS(ESI): Calcd. C9H9N3OS, [MþH]þm/z: 193.0543, found: 193.0542.
C9H9N3OS, [MþH]þm/z: 208.0539, found: 208.0539.
4.5.9. 5-([1,10-biphenyl]-2-yl)-4H-1,2,4-triazole-3-thiol (5i)
4.6. General procedure for the synthesis of compounds 6a6i
~
White solid, yield: 80%, m.p.: 250e252 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d
13.39 (s, 1H), 13.20 (s, 1H), 7.65e7.59 (m, 2H), 7.55e7.46
4.6.1. 3-(methylthio)-5-phenyl-4H-1,2,4-triazole (6a)
(m, 2H), 7.41e7.32 (m, 3H), 7.24e7.19 (m, 2H). 13C NMR (100 MHz,
The mixture of 5a (1 eq.), CH3I (1 eq.) and Et3N (1 eq.) in
methanol was stirred at rt for 2 h and monitored by TLC (PE/
EA ¼ 1:1). After completion of the reaction, add dH2O and then
filter the mixture to afford compound 6a as brown solid, yield: 71%,
DMSO‑d6)
d 141.3, 139.7, 130.6, 130.4, 128.7, 128.2, 127.6, 127.3. HR-
MS(ESI): Calcd. C14H11N3S, [MþNa]þm/z: 276.0566, found: 276.0567.
4.5.10. 5-(3-bromophenyl)-4H-1,2,4-triazole-3-thiol (5j)
m.p.: 97e98 ꢁC. 1H NMR (400 MHz, DMSO‑d6)
d 8.01e7.94 (m, 2H),
White solid, yield: 81%, m.p.: 262e264 ꢁC. 1H NMR (400 MHz,
7.56e7.44 (m, 3H), 2.62 (s, 3H). 13C NMR (100 MHz, DMSO‑d6)
DMSO‑d6)
d
13.75 (s, 1H), 13.54 (s, 1H), 8.11 (t, J ¼ 1.7 Hz, 1H),
d
129.8, 128.9, 125.8, 14.1. HR-MS(ESI): Calcd. C9H9N3S, [MþH]þm/z:
7.93e7.89 (m, 1H), 7.74e7.68 (m, 1H), 7.48 (t, J ¼ 7.9 Hz, 1H). 13C
192.0590, found: 192.0591.
NMR (100 MHz, DMSO‑d6)
d 167.3, 149.0, 133.2, 131.2, 128.2, 127.7,
124.6, 122.2. HR-MS(ESI): Calcd. C8H6BrN3S, [MþH]þm/z: 255.9539,
4.6.2. 3-Phenyl-5-(prop-2-yn-1-ylthio)-4H-1,2,4-triazole (6b)
The mixture of 5a (1 eq.), bromopropyne (1 eq.) and Et3N (1 eq.)
in THF was stirred at rt for 2 h and monitored by TLC (PE/EA ¼ 1:1).
After completion of the reaction, add dH2O and then filter the
mixture to afford compound 6b as white solid, yield: 75%, m.p.:
found: 255.9533.
4.5.11. 5-(3-methoxyphenyl)-4H-1,2,4-triazole-3-thiol (5k)
White solid, yield: 71%, m.p.: 241e243 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d
13.70 (s, 1H), 13.56 (s, 1H), 7.88e7.82 (m, 2H), 7.10e7.04
166.5, 160.9,
89e91 ꢁC. 1H NMR (400 MHz, DMSO‑d6)
d
14.58 (s, 1H), 8.00e7.94
(m, 2H), 3.82 (s, 3H). 13C NMR (100 MHz, DMSO‑d6)
d
(m, 2H), 7.59e7.44 (m, 3H), 4.01 (s, 2H), 3.20 (s, 1H). 13C NMR
150.2, 127.3, 117.9, 114.5, 55.3. HR-MS(ESI): Calcd. C9H9N3OS,
(100 MHz, DMSO‑d6) d 130.0, 129.0, 126.0, 80.1, 74.0, 19.9. HR-
[MþH]þm/z: 208.0539, found: 208.0538.
MS(ESI): Calcd.
238.0405.
C
11H9N3S, [MþNa]þm/z: 238.0409, found:
4.5.12. 5-(3-aminophenyl)-4H-1,2,4-triazole-3-thiol (5l)
Yellow solid, yield: 87%, m.p.: 263e265 ꢁC. 1H NMR (400 MHz,
4.6.3. 3-(allylthio)-5-phenyl-4H-1,2,4-triazole (6c)
DMSO‑d6)
d
13.65 (s, 1H), 13.55 (s, 1H), 7.15e7.08 (m, 2H), 7.03 (d,
The mixture of 5a (1 eq.), bromopropene (1 eq.) and Et3N (1 eq.)
in THF was stirred at rt for 2 h and monitored by TLC (PE/EA ¼ 1:1).
After completion of the reaction, add dH2O and then filter the
mixture to afford compound 6c as white solid, yield: 80%, m.p.:
J ¼ 7.8 Hz, 1H), 6.70e6.66 (m, 1H), 5.35 (s, 2H). 13C NMR (100 MHz,
DMSO‑d6)
d 166.6, 150.8, 149.1, 129.5, 125.9, 116.2, 113.2, 110.4. HR-
MS(ESI): Calcd. C8H8N4S, [MþH]þm/z: 193.0542, found: 193.0543.
109e110 ꢁC. 1H NMR (400 MHz, DMSO‑d6)
d 14.48 (s, 1H), 8.03e7.92
4.5.13. 5-(3-(morpholinosulfonyl)phenyl)-4H-1,2,4-triazole-3-thiol
(5m)
(m, 2H), 7.60e7.38 (m, 3H), 6.05e5.89 (m, 1H), 5.31e5.23 (m, 1H),
5.09 (d, J ¼ 9.9 Hz, 1H), 3.91e3.77 (m, 2H). 13C NMR (100 MHz,
White solid, yield: 72%, m.p.: 245e247 ꢁC. 1H NMR (400 MHz,
DMSO‑d6) d 159.1, 155.1, 134.1, 130.3, 129.1, 126.0, 117.7, 33.9. HR-
DMSO‑d6)
d
8.28e8.21 (m, 2H), 7.88e7.76 (m, 2H), 3.69e3.58 (m,
167.5,
MS(ESI): Calcd. C11H11N3S, [MþH]þm/z: 218.0746, found: 218.0746.
4H), 2.97e2.83 (m, 4H). 13C NMR (100 MHz, DMSO‑d6)
d
148.9, 135.6, 130.5, 130.1, 129.3, 126.7, 124.5, 65.2, 45.9. HR-MS(ESI):
4.6.4. 3-(benzylthio)-5-phenyl-4H-1,2,4-triazole (6d)
Calcd. C12H14N4O3S2, [MþNa]þm/z: 349.0400, found: 349.0401.
The mixture of 5a (1 eq.), benzyl bromide (1 eq.) and KOH (1 eq.)
in ethanol was stirred at 90 ꢁC for 4 h and monitored by TLC (PE/
EA ¼ 4:1). When the reaction finished, flash column chromatog-
raphy was used to purify the mixture to get compound 6d as white
solid, yield: 60%, m.p.: 99e100 ꢁC. 1H NMR (400 MHz, DMSO‑d6)
4.5.14. 5-(benzo[d] [1,3]dioxol-5-yl)-4H-1,2,4-triazole-3-thiol (5n)
White solid, yield: 73%, m.p.: 246e248 ꢁC. 1H NMR (400 MHz,
DMSO‑d6)
d 13.68 (s, 1H), 13.59 (s, 1H), 7.47e7.43 (m, 1H), 7.40 (d,
J ¼ 1.6 Hz, 1H), 7.06 (d, J ¼ 8.1 Hz, 1H), 6.11 (s, 2H). 13C NMR
d
14.40 (s, 1H), 8.00e7.96 (m, 2H), 7.55e7.45 (m, 3H), 7.44e7.40 (m,
(100 MHz, DMSO‑d6)
d 166.6, 150.1, 149.1, 147.9, 120.3, 119.3, 108.8,
2H), 7.34e7.28 (m, 2H), 7.27e7.22 (m, 1H), 4.43 (s, 2H). 13C NMR
105.6, 101.7. HR-MS(ESI): Calcd. C9H7N3O2S, [MþH]þm/z: 222.0332,
(100 MHz, DMSO‑d6) d 159.4, 155.1, 138.1, 130.4, 129.1, 128.8, 128.3,
found: 222.0331.
127.1, 126.0, 125.7, 35.2. HR-MS(ESI): Calcd. C15H13N3S, [MþNa]þm/
z: 290.0722, found: 290.0723.
4.5.15. 5-(p-tolyl)-4H-1,2,4-triazole-3-thiol (5o)
White solid, yield: 72%, m.p.: 245e247 ꢁC. 1H NMR (400 MHz,
4.6.5. N-phenyl-2-((5-phenyl-4H-1,2,4-triazol-3-yl)thio)acetamide
(6e)
The mixture of 5a (1 eq.), 2-bromo-N-phenylacetamide (1 eq.)
and NaOH (1 eq.) in methanol was stirred at 80 ꢁC for 4 h and
monitored by TLC (MeOH/DCM ¼ 1:10). After completion of the
DMSO‑d6)
d
13.76 (s, 1H), 13.61 (s, 1H), 7.80 (d, J ¼ 7.6 Hz, 2H), 7.32
(d, J ¼ 7.5 Hz, 2H), 2.35 (s, 3H). 13C NMR (100 MHz, DMSO‑d6)
d
167.3, 150.7, 140.9, 130.1, 126.1, 123.2, 21.4. HR-MS(ESI): Calcd.
C9H9N3S, [MþH]þm/z: 192.0590, found: 192.0591.
13