Molecules 2018, 23, 1043
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3.2.1. General Procedure for the Synthesis of the Target Compounds 5a–h
The appropriate N-acetylisatin 4a–d (1 mmol) was added to a suspension containing the proper
acid hydrazide 3a,b (1 mmol) in acetonitrile (15 mL). The reaction mixture was heated to reflux for
two hours, cooled to room temperature, and filtered. The collected solid was dried and re-crystallized
from ethanol to give the title compounds 5a–h.
N-(2-{[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide (5a): Yellow powder;
m.p. 249–250 ◦C (yield 58%); 1H-NMR (DMSO-d6):
δ (ppm) 2.20 (s, 3H, CH3), 7.09 (t, J = 7.5 Hz, 1H,
Ar-H), 7.24 (t, J = 7.5 Hz, 1H, Ar-H), 7.27 (d, J = 1.5 Hz, 1H, CH-3-indole), 7.31 (t, J = 7.5 Hz, 1H, Ar-H),
7.47 (d, J = 8.5 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.73 (dd, J = 1.5, 8.5 Hz, 1H, Ar-H), 8.11
(dd, J = 1.0, 8.0 Hz, 1H, Ar-H), 8.21 (d, J = 8.0 Hz, 1H, Ar-H), 10.71 (s, 1H, NH), 10.75 (s, 1H, NH), 10.90
(s, 1H, NH), 11.85 (s, 1H, NH-indole); 13C-NMR (DMSO-d6):
δ (ppm) 24.9 (CH3), 104.2, 112.9, 120.5,
121.5, 121.9, 122.3, 123.6, 124.4, 127.4, 129.5, 133.5, 135.9, 137.3, 140.3 (Ar-CH and Ar-C), 158.3, 164.5,
−
169.6, 192.7 (4
found: 363.1028 (M − H).
N-(4-Bromo-2-{[2-(1H-indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide (5b): Yellow
×
C=O); MS m/z (ESI): 363 [M
−
H] ; HR-MS (MALDI) calcd for C19H16N4O4: 363.1093,
◦
powder; m.p. 261–263 C (yield 56%); 1H-NMR (DMSO-d6):
δ (ppm) 2.19 (s, 3H, CH3), 7.08 (t, J = 7.5 Hz,
1H, Ar-H), 7.24 (t, J = 7.5 Hz, 1H, Ar-H), 7.27 (d, J = 1.5 Hz, 1H, CH-3-indole), 7.49 (d, J = 8.5 Hz, 1H,
Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.89 (dd, J = 2.0, 8.5 Hz, 1H, Ar-H), 7.96 (d, J = 8.5 Hz, 1H, Ar-H),
8.08 (d, J = 2.5 Hz, 1H, Ar-H), 10.65 (s, 1H, NH), 10.68 (s, 1H, NH), 10.91 (s, 1H, NH), 11.83 (s, 1H,
NH-indole); 13C-NMR (DMSO-d6):
δ
(ppm) 24.7 (CH3), 104.3, 112.9, 114.0, 115.4, 120.2, 122.3, 123.7,
124.4, 127.3, 129.5, 133.4, 134.6, 137.5, 138.6 (Ar-CH and Ar-C), 158.3, 160.6, 169.4, 192.6 (4× C=O);
MS m/z (ESI): 441 [M
H]−, 442 [(M + 1) H]−, 443[(M + 2) H]−; HR-MS (MALDI) calcd for
−
−
−
C19H15BrN4O4: 441.0198, found: 441.0206 (M − H).
N-(4-Chloro-2-{[2◦-(1H-indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide (5c): Yellow
δ (ppm) 2.19 (s, 3H, CH3), 7.08 (t, J = 7.5 Hz,
powder; m.p. 259–260 C (yield 77%); 1H-NMR (DMSO-d6):
1H, Ar-H), 7.24 (t, J = 7.5 Hz, 1H, Ar-H), 7.27 (d, J = 1.5 Hz, 1H, CH-3-indole), 7.48 (d, J = 8.0 Hz, 1H,
Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.77 (dd, J = 2.5, 8.5 Hz, 1H, Ar-H), 7.99 (d, J = 2.5 Hz, 1H, Ar-H),
7.02 (d, J = 8.5 Hz, 1H, Ar-H), 10.66 (s, 1H, NH), 10.69 (s, 1H, NH), 10.91 (s, 1H, NH), 11.83 (s, 1H,
NH-indole); 13C-NMR (DMSO-d6):
δ
(ppm) 24.7 (CH3), 104.3, 112.9, 120.5, 122.3, 123.8, 124.4, 124.8,
127.4, 127.7, 129.5, 131.7, 134.9, 137.2, 138.2 (Ar-CH and Ar-C), 160.9, 163.4, 169.7, 190.2 (4 C=O);
MS m/z (ESI): 397 [M
H]−, 398 [(M + 1) H]−, 399 [(M + 2) H]−; HR-MS (MALDI) calcd for
C19H15ClN4O4: 397.0704, found: 397.0738 (M − H).
N-(4-Fluoro-2-{[2-(1H-indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl}phenyl)acetamide (5d): Yellow
×
−
−
−
◦
powder; m.p. 268–270 C(yield 73%); 1H-NMR (DMSO-d6):
δ (ppm) 2.17 (s, 3H, CH3), 7.08 (t, J = 7.5 Hz,
1H, Ar-H), 7.24 (t, J = 8.0 Hz, 1H, Ar-H), 7.27 (d, J = 1.5 Hz, 1H, CH-3-indole), 7.47 (d, J = 8.5 Hz, 1H,
Ar-H), 7.60 (ddd, J = 2.5, 3.0, 8.5 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.84 (dd, J = 3.0, 9.5 Hz,
1H, Ar-H), 7.97–7.99 (m, 1H, Ar-H), 10.55 (s, 1H, NH), 10.69 (s, 1H, NH), 10.89 (s, 1H, NH), 11.85 (s, 1H,
NH-indole); 13C-NMR (DMSO-d6):
δ
(ppm) 24.5 (CH3), 104.3, 112.9, 118.4, 118.5, 120.5, 122.2, 122.3,
124.4, 127.4, 129.5, 130.4, 133.2, 135.6, 137.7 (Ar-CH and Ar-C), 161.1, 163.6, 169.6, 190.1 (4 C=O);
H]−; HR-MS (MALDI) calcd for C19H15FN4O4: 381.0999, found: 381.0951
×
MS m/z (ESI): 381 [M
(M − H).
−
N-{2-[{2-[(5-Methoxy-1H-indol-2yl)carbonyl]hydrazinyl}(oxo)acetyl]phenyl}acetamide (5e): Pale
yellow powder; m.p. 228-230 ◦C (yield 52%); 1H-NMR (DMSO-d6):
δ (ppm) 2.19 (s, 3H, CH3), 3.78 (s,
3H, OCH3), 6.90 (dd, J = 2.5, 8.5 Hz, 1H, Ar-H), 7.15 (d, J = 1.0 Hz, 1H, Ar-H), 7.19 (s, 1H, CH-3-indole),
7.31(t, J = 7.5 Hz, 1H, Ar-H), 7.35 (d, J = 9.0 Hz, 1H, Ar-H), 7.72 (t, J = 8.0 Hz, 1H, Ar-H), 8.11 (d,
J = 8.0 Hz, 1H, Ar-H), 8.20 (d, J = 8.5 Hz, 1H, Ar-H), 10.66 (s, 1H, NH), 10.75 (s, 1H, NH), 10.89 (s, 1H,
NH), 11.71 (s, 1H, NH-indole); 13C-NMR (DMSO-d6):
δ
(ppm) 24.9 (CH3), 55.7 (OCH3), 102.6, 103.9,
113.7, 115.8, 121.5, 121.9, 123.6, 127.8, 129.8, 132.5, 133.5, 135.9, 140.3, 154.4 (Ar-CH and Ar-C), 160.9,
164.5, 169.6, 192.7 (4 C=O); MS m/z (ESI): 393 [M
H]−; HR-MS (MALDI) calcd for C20H18N4O5:
393.1199, found: 393.1139 (M − H).
×
−