A. You et al. / Bioorg. Med. Chem. 23 (2015) 924–931
927
(m, 2H), 1.46–1.17 (m, 10H), 0.86 (t, J = 6.7 Hz, 3H). 13C NMR
(75 MHz, DMSO-d6) d: 178.4, 156.8, 153.6, 133.1, 129.1, 114.1,
67.3, 40.0, 31.2, 30.7, 28.7, 28.7, 28.7, 25.5, 22.1, 16.6, 13.9. Anal.
Calcd for C19H31N3OS: C, 65.29; H, 8.94; N, 12.02. Found: C,
65.22; H, 8.82; N, 12.01. ESI-MS m/z = 350.2 [M+1]+.
(75 MHz, DMSO-d6) d: 178.4, 172.5, 156.6, 153.6, 133.3, 129.2,
114.2, 66.3, 59.8, 40.0, 30.6, 30.1, 24.2, 16.6, 14.1. Anal. Calcd for
C
17H25N3O3S: C, 58.09; H, 7.17; N, 11.96. Found: C, 58.06; H,
7.18; N, 12.04. ESI-MS m/z = 352.3 [M+1]+.
2.2.2.15.
bazide (8b).
1-(4-Methoxyphenyl)propan-2-ylidenethiosemicar-
Solid product. 1H NMR (300 MHz, DMSO) d 9.97
2.2.2.9.
micarbazide (7j).
4-(4-(Pentan-3-yl)oxyphenyl)butan-2-ylidenethiose-
Solid product, yield 88%, mp 111–112 °C.
(s, 1H), 8.07 (s, 1H), 7.59 (s, 1H), 7.13 (d, J = 7.4 Hz, 2H), 6.85 (d,
J = 7.0 Hz, 2H), 3.71 (s, 3H), 3.43 (s, 2H), 1.79 (s, 3H). 13C NMR
(75 MHz, DMSO-d6) d: 178.6, 158.0, 153.1, 130.0, 129.0, 114.0,
55.0, 43.6, 15.8. It was identified with the reported data.11a
1H NMR (300 MHz, DMSO-d6) d: 9.95 (s, 1H), 8.06 (s, 1H), 7.46 (s,
1H), 7.10 (d, J = 8.6 Hz, 2H), 6.81 (d, J = 8.5 Hz, 2H), 4.17–4.10(m,
1H), 2.81–2.69 (m, 2H), 2.57–2.46 (m, 2H), 1.91 (s, 3H), 1.66–
1.50 (m, 4H), 0.88 (t, J = 7.4 Hz, 6H). 13C NMR (75 MHz, DMSO-d6)
d: 178.5, 156.4, 153.6, 133.1, 129.2, 115.5, 79.0, 40.0, 38.5, 30.6,
25.5, 16.7, 9.3. Anal. Calcd for C16H25N3OS: C, 62.50; H, 8.20; N,
13.67. Found: C, 62.55; H, 8.11; N, 13.69. ESI-MS m/z = 308.3
[M+1]+.
2.2.2.16. 1-(4-Pentyloxyphenyl)propan-2-ylidenethiosemicar-
bazide (8c).
Solid product, yield 81%, mp 137–139 °C. 1H
NMR (300 MHz, DMSO-d6) d: 10.00 (s, 1H), 8.10 (s, 1H), 7.62
(s, 1H), 7.14 (d, J = 7.8 Hz, 2H), 6.86 (d, J = 7.7 Hz, 2H), 3.91
(t, J = 6.4 Hz, 2H), 3.44 (s, 2H), 1.80 (s, 3H), 1.76–1.65 (m, 2H),
1.42–1.27 (m, 4H), 0.89 (t, J = 6.7 Hz, 3H). 13C NMR (75 MHz,
DMSO-d6) d: 178.7, 157.4, 153.1, 129.9, 128.8, 114.4, 67.3, 43.6,
28.4, 27.7, 21.9, 15.7, 13.9. Anal. Calcd for C15H23N3OS: C, 61.40;
H, 7.90; N, 14.32. Found: C, 61.15; H, 7.81; N, 14.41. ESI-MS
m/z = 294.3 [M+1]+.
2.2.2.10.
bazide (7k).
4-(4-Benzyloxyphenyl)butan-2-ylidenethiosemicar-
Solid product, yield 92%, mp 136–137 °C. 1H
NMR (300 MHz, DMSO-d6) d: 9.96 (s, 1H), 8.06 (s, 1H), 7.50–7.27
(m, 6H), 7.14 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 6.7, 2H),, 5.05 (s, 2H),
2.83–2.72 (m, 2H), 2.54–2.46 (m, 2H), 1.90 (s, 3H). 13C NMR
(75 MHz, DMSO-d6) d: 178.4, 156.5, 153.6, 137.2, 133.5, 129.2,
128.4, 127.7, 127.6, 114.5, 69.1, 39.9, 30.6, 16.7. Anal. Calcd for
2.2.2.17. 1-(4-Benzyloxyphenyl)propan-2-ylidenethiosemicar-
bazide (8d).
C
18H21NOS: C, 66.02; H, 6.46; N, 12.83. Found: C, 66.12; H, 6.49;
Solid product, yield 83%, mp 153–154 °C. 1H
N, 12.81. ESI-MS m/z = 328.3 [M+1]+.
NMR (300 MHz, DMSO-d6) d: 10.00 (s, 1H), 8.10 (s, 1H), 7.62 (s,
1H), 7.48–7.31 (m, 5H), 7.17 (d, J = 8.6 Hz, 2H), 6.96 (d, J = 9.0,
2H), 5.07 (s, 2H), 3.43 (s, 2H), 1.80 (s, 3H). 13C NMR (75 MHz,
DMSO-d6) d: 178.7, 157.1, 153.1, 137.1, 130.0, 129.2, 128.4,
127.8, 127.7, 114.8, 69.1, 43.6, 15.8. Anal. Calcd for C17H19N3OS:
C, 65.15; H, 6.11; N, 13.41. Found: C, 65.32; H, 6.10; N, 13.01.
ESI-MS m/z = 314.1 [M+1]+.
2.2.2.11. 4-(4-(4-BromoBenzyloxy)phenyl)butan-2-ylidenethi-
osemicarbazide (7l).
Solid product, yield 90%, mp 174–
175 °C. 1H NMR (300 MHz, DMSO-d6) d: 9.91 (s, 1H), 8.02 (s, 1H),
7.56 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 7.8 Hz, 3H), 7.11 (d, J = 8.2 Hz,
2H), 6.87 (d, J = 7.9 Hz, 2H), 5.03 (s, 2H), 2.81–2.70 (m, 2H), 2.49–
2.44 (m, 2H), 1.89 (s, 3H).13C NMR (75 MHz, DMSO-d6) d: 178.4,
156.3, 153.6, 136.7, 133.7, 131.3, 129.7, 129.2, 120.8, 114.6, 68.3,
39.9, 30.6, 16.7. Anal. Calcd for C18H20BrN3OS: C, 53.20; H, 4.96;
N, 10.34. Found: C, 53.22; H, 4.95; N, 10.25. SI-MS m/z = 406.1
2.2.2.18.
ylidenethiosemicarbazide (8e).
1-(4-(3-Ethoxycarbonyl)propoxyphenyl)proptan-2-
Yellowish solid product,
yield 78%, mp 93–94 °C. 1H NMR (300 MHz, DMSO-d6) d: 9.99 (s,
1H), 8.09 (s, 1H), 7.62 (s, 1H), 7.15 (d, J = 8.6 Hz, 2H), 6.86 (d,
J = 8.6 Hz, 2H), 4.10–4.01 (m, 2H), 3.95 (t, J = 6.3 Hz, 2H), 3.44 (s,
2H), 2.44 (t, J = 7.3 Hz, 2H), 2.00–1.91 (m, 2H), 1.80 (s, 3H), 1.17
(t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d: 178.7, 172.5,
157.2, 153.1, 129.9, 129.0, 114.4, 66.4, 59.8, 43.6, 30.1, 24.2, 15.7,
14.1. ESI-MS m/z = 338.3 [M+1]+.
[M+1]+
.
2.2.2.12. 4-(4-(3-Phenylpropyl)phenyl)butan-2-ylidenethiose-
micarbazide (7m).
Solid product, yield 78%, mp 131–132 °C.
1H NMR (300 MHz, DMSO-d6) d: 9.95 (s, 1H), 8.05 (s, 1H), 7.44 (s,
1H), 7.33–7.17 (m, 5H), 7.12 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 6.7,
2H), 3.90 (t, J = 8.5, 2H), 2.82–2.68 (m, 4H), 2.55–2.44 (m, 2H),
2.05–1.94 (m, 2H), 1.91 (s, 3H). 13C NMR (75 MHz, DMSO-d6) d:
178.4, 156.7, 153.6, 141.4, 133.2, 129.2, 128.3 (overlapped peak),
125.8, 114.2, 66.5, 40.0, 31.5, 30.7, 30.4, 16.7. Anal. Calcd for
2.2.2.19. 4-(4-Methoxyphenyl)butan-2-ylidenethiocarbonohyd-
razide (9b).
Solid product, yield 79%, mp 167–168 °C. 1H NMR
(300 MHz, DMSO-d6) d: 9.16 (s, 2H), 7.07 (d, J = 7.9 Hz, 2H), 6.81 (d,
J = 7.5 Hz, 2H), 4.73 (s, 2H), 3.69 (s, 3H), 2.52 (t, J = 9.6 Hz, 2H), 1.56
(t, J = 8.9 Hz, 2H), 1.09 (s, 3H). 13C NMR (75 MHz, DMSO-d6) d:
176.8, 160.1, 148.4, 130.4, 128.7, 114.4, 67.7, 31.2, 19.2, 14.2.
ESI-MS m/z = 267.0 [M+1]+.
C
20H25N3OS: C, 67.57; H, 7.09; N, 11.82. Found: C, 67.49; H, 7.07;
N, 11.81. ESI-MS m/z = 256.2 [M+1]+.
2.2.2.13.
ethiosemicarbazide (7n).
4-(4-Ethoxycarbonylmethylphenyl)butan-2-yliden-
Solid product, yield 85%, mp 124–
125 °C. 1H NMR (300 MHz, DMSO-d6) d: 9.95 (s, 1H), 8.05 (s, 1H),
7.44 (s, 1H), 7.14 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 4.72
(s, 2H), 4.20–4.12 (m, 2H), 2.84–2.72 (m, 2H), 2.55–2.44 (m, 2H),
1.91 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, DMSO-d6)
d: 178.4, 168.8, 155.8, 153.6, 134.1, 129.2, 114.3, 64.7, 60.5, 39.9,
30.6, 16.7, 14.0. Anal. Calcd for C15H21N3O3S: C, 55.71; H, 6.54; N,
12.99. Found: C, 55.95; H, 6.51; N, 13.06. ESI-MS m/z = 324.3
[M+1]+.
2.2.2.20. 4-(4-Butoxyphenyl)butan-2-ylidenethiocarbonohyd-
razide (9c).
Solid product, yield 73%, mp 147–148 °C. 1H
NMR (300 MHz, DMSO-d6) d: 9.15 (s, 2H), 7.05 (d, J = 7.2 Hz, 2H),
6.80 (d, J = 7.2 Hz, 2H), 4.72 (s, 2H), 3.89 (t, J = 6.1 Hz, 2H), 2.50
(s, 2H), 1.74 – 1.60 (m, 2H), 1.58–1.49 (m, 2H), 1.41 (m, 2H), 1.09
(s, 3H), 0.91 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d:
173.0, 157.3, 134.3, 129.7, 129.5, 114.7, 67.5, 65.6, 31.3, 28.8,
20.5, 19.2, 14.2. ESI-MS m/z = 309.1 [M+1]+.
2.2.2.14. 4-(4-(3-Ethoxycarbonylpropyl)phenyl)butan-2-yliden-
2.2.2.21.
hydrazide (10a).
1-(4-Methoxyphenyl)propan-2-ylidenethiocarbono-
ethiosemicarbazide (7o).
Solid product, yield 85%, mp 94–
95 °C. 1H NMR (300 MHz, DMSO-d6) d: 9.95 (s, 1H), 8.05 (s, 1H),
7.44 (s, 1H), 7.12 (d, J = 8.6 Hz, 2H), 6.81 (d, J = 8.6 Hz, 2H), 4.10–
4.03 (m, 2H), 3.99–3.88 (m, 2H), 2.82–2.70 (m, 2H), 2.55–2.38
(m, 4H), 2.01–1.86 (m, 5H), 1.17 (t, J = 7.1 Hz, 3H). 13C NMR
White crystals, yield 74%, mp 179–180 °C.
1H NMR (300 MHz, DMSO-d6) d: 9.97 (s, 1H), 9.38 (s, 1H), 7.15
(d, J = 7.7 Hz, 2H), 6.85 (d, J = 7.4 Hz, 2H), 4.81 (s, 2H), 3.71
(s, 3H), 3.43 (s, 2H), 1.76 (s, 3H). 13C NMR (75 MHz, DMSO-d6)