D.C. Santos, et al.
Bioorganic&MedicinalChemistry28(2020)115470
4.2.1. N’-Benzylidene Isonicotinohydrazide (1a)
4.2.8. N’-(2-Hydroxybenzylidene) Isonicotinohydrazide (1 h)
white solid, yield 84%, 98.9% HPLC purity, MP: 189–190 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.02 (s, 1H, NH), 8.48 (s, 1H, CH = N),
8.77 (d, 2H, J = 3.0 Hz, Ar-H), 7.82 (d, 2H, J = 6.0 Hz, Ar-H), 7.73 (d,
2H, J = 3.0 Hz, Ar-H), 7.45–7.16 (m, 3H, Ar-H). 13C NMR (100 MHz,
DMSO‑d6) δ: 161.63, 150.33, 149.03, 140.46, 134.02, 130.38, 128.87,
127.26, 121.53. HRMS (ESI) m/z calcd for C13H11N3O [M + H]:
226.2459, found: 226.0974.
white solid, yield 90% 98.1% HPLC purity, MP: 244–246 °C. 1H
NMR (500 MHz, DMSO‑d6) δ: 11.88 (s, 1H, NH), 10.00 (s,1H, OH), 8.79
(d, 2H, J = 5.5 Hz, Ar-H), 8.38 (s,1H, CH = N), 7.83 (d, 2H,
J = 6.0 Hz, Ar-H), 7.61 (d, 2H, J = 8.5 Hz, Ar-H), 6.87 (d, 2H,
J = 8.5 Hz, Ar-H). 13C NMR (125 MHz, DMSO‑d6) δ: 161.27, 159.70,
150.28, 149.49, 145.01, 140.67, 128.62, 124.98, 123.13, 121.48,
115.76. HRMS (ESI) m/z calcd for C13H11N3O2 [M + H]: 242.2453,
found: 242.0913.
4.2.2. N’-(4-Dimethylaminobenzylidene) Isonicotinohydrazide (1b)
yellow solid, yield 81%, 98.9% HPLC purity, MP: 203–205 °C. 1H
NMR (500 MHz, DMSO‑d6) δ: 11.82 (s, 1H, NH), 8.78 (d, 2H,
J = 5.0 Hz, Ar-H), 8.33 (s, 1H, CH = N), 7.83 (d, 2H, J = 5.0 Hz, Ar-
H), 7.58 (d, 2H, J = 10.0 Hz, Ar-H), 6.78 (d, 2H, J = 10.0 Hz, Ar-H),
2.98 (s, 6H, N-CH3). 13C NMR (125 MHz, DMSO‑d6) δ: 167.57, 161.51,
151.88, 150.32, 149.92, 141.10, 128.63, 121.94, 121.66, 111.98.
HRMS (ESI) m/z calcd for C13H11N3O [M + H]: 269.3137, found:
269.1396.
4.2.9. N’-(2-Hydroxy-5-bromobenzylidene) Isonicotinohydrazide (1i)
yellowish solid, yield 88%, 98.8% HPLC purity, MP: 256–258 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.37 (s, 1H, NH), 11.15 (s, 1H, OH),
8.82 (d, 2H, J = 5.3 Hz, Ar-H), 8.67 (s, 1H, CH = N), 7.87 (d, 2H,
J = 6.0 Hz, Ar-H), 7.84 (d, 1H, J = 2.5 Hz, Ar-H), 7.47 (dd, 1H, J = 2.5
and 8.7 Hz, Ar-H), 6.93 (d, 1H, J = 8.7 Hz, Ar-H). 13C NMR (100 MHz,
DMSO‑d6) δ: 161.48, 156.46, 150.37, 146.34, 139.89, 133.89, 130.12,
121.52, 121.29, 118.70, 110.55. HRMS (ESI) m/z calcd for
C13H10BrN3O2 [M + H]: 320.1414, found: 320.0013.
4.2.3. N’-(4-fluorobenzylidene) Isonicotinohydrazide (1c)
white solid, yield 65%, 98.5% HPLC purity, MP: 184–186 °C. 1H
NMR (500 MHz, DMSO‑d6) δ: 12.10 (s, 1H, NH), 8.81 (d, 2H,
J = 6.0 Hz, Ar-H), 8.48 (s, 1H, CH = N), 7.84 (m, 4H, Ar-H), 7.34 (m,
2H, Ar-H). 13C NMR (125 MHz, DMSO‑d6) δ: 164.30, 161.57, 150.26,
147.94, 140.64, 130.64, 129.47, 121.65, 115.90. HRMS (ESI) m/z calcd
for C13H10FN3O [M + H]: 244.2364, found: 244.0880.
4.2.10. N’-(2,5-Dihydroxybenzylidene) isonicotinohydrazide (1j)
yellow solid, yield 80%, 98.3% HPLC purity, MP: 294–295 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.20 (s, 1H, NH), 10.23 (s, 1H, OH),
9.03 (s, 1H, OH), 8.81 (d, 2H, J = 1.5 and 4.5 Hz, Ar-H), 8.64 (s, 1H,
CH = N), 7.87 (dd, 2H, J = 1.6 and 4.5 Hz, Ar-H), 7.07 (d, 1H,
J = 1.7 Hz, Ar-H), 6.78 (d, 2H, J = 2.5 Hz, Ar-H). 13C NMR (100 MHz,
DMSO‑d6) δ: 161.32, 150.38, 150.32, 149.98, 148.35, 140.16, 121.54,
119.38, 119.08, 117.19, 113.41. HRMS (ESI) m/z calcd for C13H11N3O3
[M + H]: 258.2447, found: 258.0863.
4.2.4. N’-(4-Methoxybenzylidene) Isonicotinohydrazide (1d)
white solid, yield 75%, 97,5.% HPLC purity, MP: 171–173 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 11.95 (s, 1H, NH), 8.80 (dd, 2H, J = 1.5
and 4.5 Hz, Ar-H), 8.42 (s, 1H, CH = N), 7.84 (dd, 2H, J = 1.5 and
4.4 Hz, Ar-H), 7.72 (d, 2H, J = 8.7 Hz, Ar-H), 7.05 (d, 2H, J = 8.7 Hz,
Ar-H), 3.82 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO‑d6) δ: 161.40,
161.08, 150.30, 148.92, 140.62, 128.92, 126.56, 121.50, 114.39,
55.32. HRMS (ESI) m/z calcd for C14H13N3O2 [M + H]: 256.27192,
found: 256.108053.
4.2.11. N’-(3-Hydroxy-4-methoxybenzylidene) isonicotinohydrazide (1 k)
yellow solid, yield 80%, 98.8% HPLC purity, MP: 226–228 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 11.89 (s, 1H, NH), 9.62 (s, 1H, OH), 8.79
(d, 2H, J = 5.9 Hz, Ar-H), 8.36 (s, 1H, CH = N), 7.83 (dd, 2H, J = 1.5
and 4.5 Hz, Ar-H), 7.34 (d, 1H, J = 1.7 Hz, Ar-H), 7.14 – 7.12 (dd, 1H,
J = 1.7 and 8.0 Hz, Ar-H), 6.88 (d, 1H, J = 8.0 Hz, Ar-H), 3.84 (s, 3H,
OCH3). 13C NMR (100 MHz, DMSO‑d6) δ: 161.32, 150.29, 149.58,
149.31, 148.08, 140.69, 125.39, 122.46, 121.50, 115.48, 109.06,
55.56. HRMS (ESI) m/z calcd for C14H13N3O3 [M + H]: 272.2713,
found: 272.1035.
4.2.5. N’-(4-Nitrobenzylidene) Isonicotinohydrazide (1e).
yellow solid, yield 92%, 98.1% HPLC purity, MP: 265–267 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.36 (s, 1H, NH), 8.82 (d, 2H,
J = 6.0 Hz, Ar-H), 8.57 (s, 1H, CH = N), 8.33 (d, 2H, J = 8.7 Hz, Ar-
4.2.12. N’-(3,4-Dichlorobenzylidene) isonicotinohydrazide (1 L)
H), 8.04 (d, 2H, J = 8.7 Hz, Ar-H), 7.85 (d, 2H, J = 6.0 Hz, Ar-H). 13
C
white solid, yield 89%, 99.2% HPLC purity, MP: 248–250 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.27 (s, 1H, NH), 8.81 (d, 2H,
J = 4.6 Hz, Ar-H), 8.44 (s, 1H, CH = N), 7.99 (d, 1H, J = 1.2 Hz, Ar-
H), 7.84 (dd, 2H, J = 1.5 and 4.5 Hz, Ar-H), 7.78 (m, 2H, Ar-H). 13C
NMR (100 MHz, DMSO‑d6) δ: 161.81, 150.35, 146.23, 140.19, 134.86,
132.57, 131.76, 131.14, 128.73, 127.00, 122.46, 121.54. HRMS (ESI)
m/z calcd for C13H9Cl2N3O [M + H]: 294.1361, found: 294.0187.
NMR (100 MHz, DMSO‑d6) δ: 161.96, 150.40, 148.05, 146.48, 140.27,
128.21, 124.09, 121.56. HRMS (ESI) m/z calcd for
C13H10N4O3
[M + H]: 271.2440, found: 271.0827.
4.2.6. N’-(4-hydroxybenzylidene) Isonicotinohydrazide (1f)
yellowish solid, yield 91%, 97.1% HPLC purity, MP: 299–301 °C. 1H
NMR (500 MHz, DMSO‑d6) δ: 11.89 (s, 1H, NH), 10.02 (s, 1H, OH),
8.79 (d, 2H, J = 1.4 and 4.5 Hz, Ar-H), 8.38 (s, 1H, CH = N), 7.83 (d,
2H, J = 1.5 and 4.5 Hz, Ar-H), 7.61 (d, 2H, d, J = 8.6 Hz, Ar-H), 6.88
(2H, d, J = 8.6 Hz, Ar-H). 13C NMR (125 MHz, DMSO‑d6) δ: 161.33,
159.73, 150.30, 149.39, 140.71, 129.12, 125.01, 121.51, 115.80.
HRMS (ESI) m/z calcd for C13H11N3O2 [M + H]: 242.2453, found:
242.0924.
4.2.13. N’-(chromone-3lmethylene) hydrazide (1 m)
white solid, yield 82%, 98.6% HPLC purity, MP: 215–217 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.16 (s, 1H, NH), 8.87 (s, 1H, Ar-H),
8.80 (dd, 2H, J = 1.4 and 4.6 Hz, Ar-H), 8.66 (s, 1H, CH = N), 8.15
(dd, 1H, J = 1.3 and 7.9 Hz, Ar-H), 7.89 (m, 3H, Ar-H), 7.75 (d, 1H,
J = 8.3 Hz, Ar-H), 7.58 (t, 1H, Ar-H). 13C NMR (100 MHz, DMSO‑d6) δ:
175.01, 161.40, 155.78, 154.85, 150.35, 141.68, 140.20, 134.75,
132.57, 131.76, 126.15, 125.21, 123.32, 121.50, 118.75, 118.09.
HRMS (ESI) m/z calcd for C16H11N3O3 [M + H]: 294.2768, found:
316.0701 (C16H11N3NaO3).
4.2.7. N’-(3-Nitrobenzylidene) Isonicotinohydrazide (1 g)
yellow solid, yield 82%, 99.5% HPLC purity, MP: 248–250 °C. 1H
NMR (400 MHz, DMSO‑d6) δ: 12.34 (s, 1H, NH), 8.82 (d, 2H,
J = 6.0 Hz, Ar-H), 8.58 (s, 1H, CH = N), 8.30 (d, 2H, J = 9.0 Hz, Ar-
H), 8.20 (s, 1H, Ar-H), 7.86 (d, 2H, J = 9.0 Hz, Ar-H), 7.77 (d, 2H,
J = 6.0 Hz, Ar-H). 13C NMR (100 MHz, DMSO‑d6) δ: 161.94, 150.39,
148.24, 146.57, 140.17, 135.89, 133.53, 130.52, 124.55, 121.58,
121.14. HRMS (ESI) m/z calcd for C13H10N4O3 [M + H]: 271.2435,
found: 271.0826.
4.2.14. Nˈ-(pyridine-2-carboxaldehyde)isonicotinoylhydrazone (1n)
white solid, yield 60%, 95% HPLC purity, MP: 160–161 °C. 1H NMR
(400 MHz, DMSO‑d6) δ: 12.27 (s, 1H, NH), 8.82 (d, 2H, J = 1,4 and 4,5
Hz, Ar-H), 8.65 (d, 1H, J = 4,7 Hz, Ar-H), 8.50 (s, 1H, CH = N), 8.03
(d, 1H, J = 7.9 Hz, Ar-H), 7.94 (td, 1H, Ar-H), 7.86 (d, 2H, J = 4.5 Hz,
6