K. Anichina et al.
Chemico-Biological Interactions 345 (2021) 109540
(bz); Analysis: Calc. for C8H10N4 (C, H, N): Calculated (%): C, 59.24; H,
6.21; N, 34.54; Found (%):C, 59.07; H, 5.95; N, 34.16.
bz), 7.53–7.51 (d, J = 7.71 Hz, 1H, Ar), 7.45–7.43 (m, 1H, Ar-bz),
7.17–7.15 (m, 1H, Ar), 7.11–7.09 (m, 1H, Ar), 7.03 (s, 1H, Ar-bz),
2.34 (s, 3H, CH3).
2.2.5. Synthesis of [(2-benzimidazolylthio)-acetyl]-hydrazine 6a
Compound 4a (0.01 mol) and hydrazine hydrate (99%, 0.025 mol) in
ethanol (10 mL) were refluxed for about 4 h on a steam bath. After
cooling, the resulting solid was filtered and washed with cold water. The
1H-benzimidazol-2-yl-hydrazine 5a was prepared and not the derivative
6a. Yield: 63%; Mp 223–225 ◦C; Rf = 0.29 (benzene-methanol 4:1, v/v);
IR (νmax/cmꢀ 1): 3314, 3273 (νNH2), 1664 (δNH), 1620 (νC=N), 1268 (νC-
N), 729 (γC-H) phenyl (bz, o-); Analysis: Calc. for C7H8N4 (C, H, N):
Calculated (%): C, 56.74; H, 5.44; N, 37.81; Found (%): C, 56.67; H,
5.24; N, 37.70.
2-(4-Fluorobenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydra-
zine (7f): Yield: 58%; Mp 276–280 ◦C; Rf = 0.42 (n-hexane: ethyl ace-
tate = 1:1, v/v); IR (νmax/cmꢀ 1) 3196 (νN-H); 3055 (νCHarom), 2921
(
νasCH3), 2862 (νsCH3), 1671 (δNH), 1603 (νC=N), 1152 (δC-F), 833 (γC-H
)
phenyl (m-), 801 (γC-H) phenyl (bz, o-); 1H NMR (600 MHz, DMSO‑d6) δ
–
–
(ppm) 11.43 (s, 1H, NH), 8.01 (s, 1H, N CH), 7.96–7.84 (m, 1H, Ar-bz),
7.28–7.25 (m, 2H, Ar), 7.10–7.09 (d, J = 7.94 Hz, 1H, Ar), 7.03 (s, 1H,
Ar), 6.80–6.75 (m, 1H, Ar-bz), 2.34 (s, 3H, CH3). 13C NMR (150 MHz,
DMSO‑d6) δ (ppm) 163.72, 162.19, 132.37, 128.84, 128.79, 116.10,
115.96.
2-((Benzo [1,3]dioxol-7-yl)methylene)-1-(1H-benzimidazol-2-yl)hy-
drazine (7g): Yield: 58%; Mp 276–280 ◦C; Rf = 0.55 (benzene: methanol
= 5:1, v/v); IR (νmax/cmꢀ 1) 3287 (νN-H); 3058 (νCHarom), 2896 (νasCH3),
2836 (νsCH3), 1654 (δNH), 1608 (νC=N); 805 (γC-H) phenyl (bz, o-), 735
2.2.6. General procedure for preparation of 2-[2-benzylidenehydrazinyl]-
1H-benzimidazole 7a-o
A mixture of 1H-benzimidazol-2-yl-hydrazine (5a,b) (0.01 mol) and
appropriate aromatic aldehyde (0.01 mol) in ethanol (99%, 20 mL) was
refluxed on water bath for about 2 h and cooled. The crystalline solid
which precipitated during the reaction, was filtered and recrystallized
from ethanol.
(γC-H) phenyl; 1H NMR (600 MHz, DMSO‑d6) δ (ppm): 11.53 (s, 1H, NH),
–
–
7.90 (s, 1H, N CH), 7.63 (d, J = 1.59 Hz, 1H, Ar-bz), 7.22–7.23 (m, 2H,
Ar), 7.08–7.10 (dd, J = 7.94 Hz, 1.60 Hz, 1H, Ar), 6.94–6.95 (m, 3H
Ar-bz), 6.07 (s, 2H, O–CH2–O).
2-(2-Fluorobenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine
(7a):
2-((benzo
[1,3]dioxol-7-yl)methylene)-1-(5(6)-methyl-1H-benzo[d]
Yield: 70%; Mp 295–297 ◦C; Rf = 0.57 (benzene: methanol = 5:1, v/v);
imidazole-2-yl)hydrazine(7h): Yield: 72%; Mp 235–240 ◦C; Rf = 0.63
(benzene: methanol = 3:1, v/v); IR (νmax/cmꢀ 1) 3057 (νCHarom), 2896
IR (νmax/cmꢀ 1) 3161 (νN-H), 3052, 3029 (νCHarom), 1645(δNH), 1635
(
νC=N), 1124 (δC-F), 783 (γC-H) phenyl (o-), 737 (γC-H) phenyl (bz, o-);
(
νasCH3), 2826 (νsCH3), 1656 (δNH), 1610 (νC=N); 791 (γC-H) phenyl (bz,
Analysis: Calc. for C14H11FN4: C, 66.13; H, 4.36; N, 22.04; Found: C,
66.33; H, 4.38; N, 7.52; 1H NMR (600 MHz, DMSO‑d6) δ (ppm) 11.63
(bs, 1H, NH), 8.25–8.22 (t, J = 14.97, 7.36 Hz, 1H, Ar), 8.22 (s, 1H,
o-), 751 (γC-H) phenyl; 1H NMR (600 MHz, DMSO‑d6) δ (ppm): 11.53 (bs,
–
–
1H, NH), 7.90 (s, 1H, N CH), 7.63 (d, J = 1.46 Hz, 1H, Ar-bz),
7.09–7.07 (m, 2H, Ar), 7.03–7.01 (s, 1H, Ar), 6.95–6.93 (d, J = 7.96
Hz, 1H Ar-bz), 6.80–6.73 (m. 1H, Ar-bz), 6.07 (s, 2H, O–CH2–O), 2.34
(d, J = 11.09 Hz, 3H, CH3).
–
N
CH), 7.42–7.38 (m, 1H, Ar), 7.29–7.27 (m, 1H, Ar), 7.25–7.24 (m,
–
3H, Ar, Ar-bz), 6.98–6.97 (m, 2H, Ar-bz); 13C NMR (150 MHz, DMSO‑d6)
δ (ppm) 159.9, 133.32, 130.95, 126.60, 125.50, 123.30, 116.32, 116.18.
2-(3-Hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine
(7i):
2-(3-Fluorobenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine
(7b):
Yield: 73%; Mp 132–136 ◦C; Rf = 0.57 (benzene: methanol = 3:1, v/v);
IR (νmax/cmꢀ 1) 3426 (νO-H); 3378 (νN-H); 3060, 3021 (νCHarom), 1648
(δNH), 1612 (νC=N); 802, 724 (γC-H) phenyl, 740 (γC-H) phenyl (bz, o-); 1H
Yield: 70%; Mp 250–255 ◦C; Rf = 0.59 (benzene: methanol = 5:1, v/v);
IR (νmax/cmꢀ 1): 3166 (νN-H), 3053, 3026 (νCHarom), 1646 (δNH), 1630
(
νC=N), 1124 (δC-F), 783, 680 (γC-H) phenyl (m-), 737 (γC-H) phenyl (bz, o-
NMR (600 MHz, DMSO‑d6) δ (ppm): 11.60 (bs, 1H, NH), 9.52 (bs, 1H,
); 1H NMR (600 MHz, DMSO‑d6) δ (ppm) 11.62 (bs, 1H, NH), 8.01 (s, 1H,
OH), 7.93 (s, 1H, N CH), 7.26–7.24 (d, J = 8.76 Hz, 2H, Ar), 7.20–7.22
–
–
N
CH), 7.80–7.78 (m, 1H, Ar), 7.54–7.52 (d, J = 7.72 Hz, 1H, Ar),
(m, 3H, Ar-Bz), 6.96 (s, 2H, Ar), 6.79 (m, 1H, Ar-bz). 13C NMR (150
MHz, DMSO‑d6) δ (ppm) 158.06, 153.85, 141.39, 136.89, 130.00,
118.13, 116.48, 113.38.
–
–
7.47–7.43 (m, 1H, Ar), 7.25–7.23 (d, J = 8.14 Hz, 2H, Ar-bz), 7.18–7.15
(m, 1H, Ar), 6.98 (s, 2H, Ar-bz). Analysis: Calc. for C14H11FN4: C, 66.13;
H, 4.36; N, 22.04; Found: C, 66.25; H, 4.30; N, 22.16.
2-(3-Hydroxybenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hy-
drazine (7j): Yield: 81%; Mp 132–136 ◦C; Rf = 0.57 (benzene: methanol
= 3:1, v/v); IR (νmax/cmꢀ 1): 3178 (νO-H); 3060 (νCHarom), 1676 (δNH),
1610 (νC=N); 1269 (νAr-O), 803 (γC-H) phenyl (m-); 1H NMR (600 MHz,
2-(4-Fluorobenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine
(7c):
Yield: 64%; Mp 258–260 ◦C; Rf = 0.53 (benzene: methanol = 5:1, v/v);
IR (νmax/cmꢀ 1): 3158 (νN-H), 3053 (νCHarom), 1655 (δNH), 1604 (νC=N),
1120 (δC-F), 827 (γC-H) phenyl (p-), 734 (γC-H) phenyl (bz, o-); Analysis:
Calc. for C14H11FN4: C, 66.13; H, 4.36; N, 22.04; Found: C, 66.23; H,
4.34; N, 22.06. 1H NMR (600 MHz, DMSO‑d6) δ (ppm) 11.57 (s, 1H, NH),
DMSO‑d6) δ (ppm): 11.50 (bs, 2H, NH), 9.53 (bs, 1H, OH), 7.93 (s, 1H,
–
–
N
CH), 7.22–7.18 (m, 3H, Ar), 7.11–7.09 (d, J = 7.83 Hz, 1H, Ar-bz),
7.04 (m, 1H Ar), 6.79–6.75 (m, 2H, Ar-bz), 2.34 (s, 3H, CH3). 13C NMR
(150 MHz, DMSO‑d6) δ (ppm) 172.61, 158.04, 153.71, 141.36, 136.92,
129.98, 118.11, 116.43, 113.34, 21.73.
–
–
8.01 (s, 1H, N CH), 7.88–7.85 (m, 2H, Ar-bz), 7.28–7.25 (m, 2H, Ar),
7.24–7.22 (d, J = 8.42 Hz, 2H, Ar), 6.96 (s, 2H, Ar-bz).
2-(2-Fluorobenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydra-
zine (7d): Yield: 63%; Mp 267–269 ◦C; Rf = 0.61 (n-hexane: ethyl ace-
tate = 1:1, v/v); IR (νmax/cmꢀ 1) 3206 (νN-H), 3038 (νCHarom), 2915
2-(4-Hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine (7k):
Yield: 63%; Mp 236–238 ◦C; Rf = 0.52 (benzene: methanol = 3:1, v/v);
IR (νmax/cmꢀ 1): 3274 (νO-H), 3056 (νCHarom), 1634 (δNH), 1604 (νC=N),
1248 (νAr-O), 803 (γC-H) phenyl (m-), 756 (γC-H) phenyl (1,3,4-), 721 (γC-
(
νasCH3), 2848 (νsCH3), 1655 (δNH), 1601 (νC=N), 1131 (δC-F), 795 (γC-H
)
phenyl (bz, o-), 758 (γC-H) phenyl (o-); Analysis: Calc. for C15H13FN4: C,
H) phenyl (bz, o-); 1H NMR (600 MHz, DMSO‑d6) δ (ppm): 11.44 (bs, 1H,
67.15; H, 4.88; N, 20.88; Found: C, 67.13; H, 4.84; N, 22.83. 1H NMR
NH), 11.24 (bs, 1H, NH), 9.76 (bs, 1H, OH), 7.93 (s, 1H, N CH),
–
–
–
–
(600 MHz, DMSO‑d ) δ (ppm) 11.50 (s, 1H, NH), 8.20 (s, 1H, N CH),
7.62–7.64 (m, 2H, Ar-bz), 7.21–7.23 (d, 2H, Ar), 6.94 (s, 2H, Ar),
6.80–6.82 (m, 2H, Ar-bz).
6
7.37–7.40 (m, 1H, Ar-bz), 7.29–7.23 (m, 2H, Ar), 7.12–7.10 (d, J = 7.90
Hz, 1H, Ar), 7.04 (s, 1H, Ar), 6.81–6.77 (m, 1H, Ar-bz), 2.34 (s, 3H,
CH3). 13C NMR (150 MHz, DMSO‑d6) δ (ppm) 161.25, 159.63, 130.84,
126.68, 125.03, 123.27, 116.30, 116,16, 110.29, 109.46.
2-(3-Methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine
(7l):
Yield: 81%; Mp 252–258 ◦C; Rf = 0.75 (benzene: methanol = 3:1, v/v);
IR (νmax/cmꢀ 1): 3232 (νN-H), 3056 (νCHarom), 2916 (νasCH3), 2843 (νsCH3),
1657 (δNH), 1610 (νC=N), 1268 (νAr-O), 789, 756 (γC-H) phenyl (m-), 734
2-(3-Fluorobenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydra-
zine (7e): Yield: 64%; Mp > 300 ◦C; Rf = 0.55 (n-hexane: ethyl acetate =
1:1, v/v); IR (νmax/cmꢀ 1) 3240 (νN-H), 2915 (νasCH3), 2845 (νsCH3), 1657
(γC-H) phenyl (bz, o-); 1H NMR (600 MHz, DMSO‑d6) δ (ppm): 11.61 (bs,
–
–
1H, NH), 8.1 (s, 1H, N CH), 7.43–7.42 (m, 1H, Ar), 7.34–7.32 (m, 2H,
–
–
(δNH), 1612 (
ν
N), 1121 (δC-F), 796 (γC-H) phenyl (bz, o-), 778 (γC-H
)
Ar-bz), 7.27–7.25 (m, 2H, Ar), 6.98 (s, 2H, Ar-bz), 6.94–6.91 (m, 1H Ar),
3.81 (s, 3H, OCH3); 13C NMR (150 MHz, DMSO‑d6) δ (ppm) 160.02,
153.88, 141.02, 137.01, 130.12, 121.11, 119.83, 115.55, 115.05,
111.59, 109.89, 55.66.
phenyl (m-), ACnalysis: Calc. for C15H13FN4: C, 67.15; H, 4.88; N, 20.88;
Found: C, 67.17; H, 4.82; N, 22.90. 1H NMR (600 MHz, DMSO‑d6) δ
–
–
(ppm) 11.46 (bs, 1H, NH), 7.99 (s, 1H, N CH), 7.79–7.77 (m, 1H, Ar-
4