Synthesis of new coumarin containing benzimidazole derivatives

Article abstract of DOI:10.3184/174751915X14449030550960

This study describes the synthesis of a new series of benzimidazoles that contain a coumarin moiety. The high yielding synthetic reaction was between hydrazide derivatives of benzimidazoles and 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-one. The reaction was performed using a very small amount of the organic solvent and without the use of a catalyst.

Full text of DOI:10.3184/174751915X14449030550960

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 NOVEMBER, 645–648
RESEARCH PAPER 645
Synthesis of new coumarin containing benzimidazole derivatives
Emre Menteşea*, Fatih Yılmaza, Fatih Mutlua and Bahittin Kahvecib
aDepartment of Chemistry, Art and Science Faculty, Recep Tayyip Erdoğan University 53100-Rize, Turkey
bDepartment of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical University 61100-Trabzon, Turkey
This study describes the synthesis of a new series of benzimidazoles that contain a coumarin moiety. The high yielding synthetic reaction
was between hydrazide derivatives of benzimidazoles and 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-one. The reaction was
performed using a very small amount of the organic solvent and without the use of a catalyst.
Keywords: coumarins, benzimidazoles, Meldrum’s acid, benzotriazoles
Coumarins are an important class of natural compounds with
a wide range of biological activities.1-4 Coumarin derivatives
have significant therapeutic potential and are a good source
of potential drug candidates with regards to their safety
and efficacy.5 They are also commonly used as additives
in fragrances, agrochemicals, insecticides and in food and
cosmetics.6 Futhermore, they have found applications as
photosensitisers, laser dyes, fluorescent indicators and optical
brighteners.7, 8
Benzimidazoles constitute an important class of molecules
in medicinal chemistry. They have anticancer,9 antiviral,10 anti-
inflammatory,11 antioxidant12 and anticoagulant properties.13
Manybenzimidazoledrugssuchasmebendazole/thiabendazole/
albendazole, norastemizole/ mizolastine, and telmisartan
have been successfully used clinically as antiparasitic,
antihistaminic and antihypertensive drugs. This has prompted
the investigation of other benzimidazole derivatives as potential
clinical therapeutics. Recently, there have been major efforts
to develop structurally novel benzimidazole compounds as
antimicrobial agents.
benzimidazole derivatives (2a–f) and the compounds 2a–f were
treated with methyl bromoacetate to synthesise methyl acetate
derivatives (3a–f). Finally, treatment of compounds 3a–f with
hydrazine monohydrate in ethanol gave hydrazide derivatives
(4a–f) which are the first intermediate compounds (Scheme 1).
To synthesise the second intermediate, 3-(1H-benzotriazol-1-
yl carbonyl)-2H-chromen-2-one (6), salicylaldehyde was reacted
with 2, 2-dimethyl-1, 3-dioxane-4, 6-dione (Meldrum’s acid),
which was prepared according to the literature,15 in ethanol to
synthesise coumarin-3-carboxylic acid (5). Then, the compound
5 was treated with 1H-benzotriazole in dichloromethane in the
presence of thionyl chloride to yield 3-(1H-benzotriazol-1-yl
carbonyl)-2H-chromen-2-one (6) (Scheme 2).
The benzotriazole group offers many advantages for synthetic
applications.16 Treatment of compounds 4a–f with compound
6 resulted in the synthesis of the target coumarin containing
benzimidazole derivatives (7a–f), using a low amount of
ethanol (10 mL) in 6 h of reflux (Scheme 3).
Spectral investigations of the newly synthesised compounds
are in accord with the proposed structures. Two NH signals
(exchangeable with D2O) were shown at about 11.20 and
With a goal of developing molecules as new therapeutic
agents, we have established a protocol for the synthesis of some
coumarin containing benzimidazoles. Our study demonstrated
that this is an efficient and environmentally safe protocol that
leads to an easy synthesis in high yield.
1
10.65 ppm in the H NMR spectra for the compounds 7a–f.
N–CH2and CH2 signals were shown at about 4.90 and 4.20
ppm, respectively. The signals of the aromatic protons of
these compounds were found to fit the proposed structure by
calculation of the J constant. In the 13C NMR spectra of these
compounds, two hydrazide carbonyl carbons were shown at
about 160 and 165 ppm. The coumarin carbonyl (coumarin
C-2) was shown at about 159 ppm. The C=N signal associated
with the benzimidazole ring was shown at about 154 ppm. The
Results and discussion
First, iminoester hydrochlorides (1a–f) were synthesised
according to the literature.14 Treatment of compounds 1a–f
with 4,5-dimethyl-o-phenylenediamine in methanol gave
H3C
NH2
NH.HCl
H3C
H3C
H3C
BrCH2COOCH3
K2CO3, Acetone
N
N
N
N
N
CH3OH
-NH4Cl
NH2NH2.H2O
C2H5OH
+
H5C2
O
H3C
NH2
N
H
H3C
H3C
H3C
O
O
O
HN
R
R
R
CH3
NH2
R
4a-f
2a-f
3a-f
1a-f
R= a:CH3, b:F, c:Cl, d:OCH3, e:NO2, f:Br
Scheme 1 Synthesis of compounds 4a–f.
N
O
O
O
O
O
O
N
N
H
N
Pyridine
O
H
N
OH
N
+
CH3
CH3
C2H5OH, 6 h
SOCl2, CH2Cl2
O
OH
O
O
O
5
6
Scheme 2 Synthesis of compound 6.
* Correspondent. E-mail: emre.mentese@erdogan.edu.tr

646 JOURNAL OF CHEMICAL RESEARCH 2015
O
O
N
H3C
N
H3C
Ethanol
N
N
+
N
N
Reflux, 6 hours
N
H3C
H3C
O
O
R
O
HN
6
NH
O
HN
R
NH2
O
4a-f
O
7a-f
R= a:CH3, b:F, c:Cl, d:OCH3, e:NO2, f:Br
Scheme 3 Synthesis of the compounds 7a–f.
temperature for 6 h. After the reaction was complete (monitored by
TLC, ethyl acetate/hexane, 3/1), the product precipitated by addition
of water. It was filtrated, dried and recrystallised from ethanol:water
(1:2).
coumarin C-3 and C-4 signals were shown at about 153 and 148
ppm, respectively. These compounds are characterised by the
anticipated number of aromatic signals in the 13C NMR spectra
and the appropriate ion peaks in their LC–MS spectra.
We report here a new protocol for the synthesis of coumarin-
containing benzimidazole derivatives. This protocol offers
shorter reaction times, simple workup procedure while using
the organic solvent in low amounts and without a need for a
catalyst.
Methyl [5,6-dimethyl-2-(4-methylbenzyl)-1H-benzimidazol-1-yl]acetate
1
(3a): Yield 2.64 g (82%); m.p. 134–135 °C; H NMR (DMSO-d6, 400
MHz): 2.23 (s, 6H), 2.27 (s, 3H), 3.49 (s, 3H), 4.13 (s, 2H), 5.03 (s, 2H),
7.07 (d, J=8.0, 2H), 7.09 (d, J=8.0, 2H), 7.18 (s, 1H), 7.33 (s, 1H). 13C NMR
(DMSO-d6, 100 MHz): 20.26, 20.48, 21.04 (CH3), 32.91 (CH2), 44.77
(NCH2), 52.54 (OCH3), 110.56, 119.20, 129.09 (2C), 129.36 (2C), 130.18,
130.84, 133.95, 134.66, 135.94, 141.18 (ArC), 153.33 (C=N), 168.75
(C=O). Anal calcd for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69; found: C,
74.44; H, 6.82; N, 8.63%. LC-MS: 323.34 [M+1].
Experimental
All the chemicals were supplied from Merck, Aldrich and Fluka.
Melting points were determined in capillary tubes on a Buchi oil
Methyl [5,6-dimethyl-2-(4-fluorobenzyl)-1H-benzimidazol-1-yl]acetate
1
heating melting point apparatus and are uncorrected. H NMR and
1
(3b): Yield 2.41 g (74%); m.p. 147–148 °C; H NMR (DMSO-d6, 400
13C NMR spectra were performed on a Varian- Mercury 400 MHz
spectrometer in DMSO-d6 using TMS as internal standard. The mass
spectra were recorded on an Agilent 1260 Infinity series Accurate-
Mass Time-of-Flight (TOF) LC/MS spectrometer. The elemental
compositions were determined on a Carlo Erba 1106 CHN analyser;
the experimental values were in agreement ( 0.4%) with calculated
ones.All reactions were monitored by TLC using precoated aluminum
sheets (silica gel 60 F 2.54 0.2 mm thickness).
MHz): 2.27 (s, 6H), 3.32 (s, 3H), 4.17 (s, 2H), 5.09 (s, 2H), 7.06–7.11 (m,
2H), 7.18 (s, 1H), 7.25–7.29 (m, 2H), 7.32 (s, 1H). 13C NMR (DMSO-d6,
100 MHz):20.25, 20.48 (CH3), 32.32 (CH2), 44.74 (NCH2), 52.56
(OCH3), 110.59, 115.37, 115.58, 119.21, 130.25, 130.92, 131.07, 133.26,
134.63, 141.13, 153.08 (C=N), 161.45 (C-F, JC-F=240.5 Hz), 168.28
(C=O). Anal calcd for C19H19FN2O2: C, 69.92; H, 5.87; N, 8.58; found: C,
69.85; H, 5.81; N, 8.53%. LC-MS: 327.40 [M+1].
Methyl [5,6-dimethyl-2-(4-chlorobenzyl)-1H-benzimidazol-1-yl]acetate
1
(3c): Yield 2.90 g (85%); m.p. 140–141°C; H NMR (DMSO-d6, 400
Synthesis of 2a–f
MHz): 2.27 (s, 6H), 3.32 (s, 3H), 4.18 (s, 2H), 5.09 (s, 2H), 7.19 (s, 1H),
7.24–7.30 (m, 2H), 7.31–7.34 (m, 3H). 13C NMR (DMSO-d6, 100 MHz):
20.25, 20.48 (CH3), 32.42 (CH2), 44.74 (NCH2), 52.57 (OCH3), 110.60,
119.22, 128.70 (2C), 130.33, 131.05, 131.61 (2C), 134.58, 136.14, 141.09
(ArC), 152.85 (C=N), 168.79 (C=O). Anal calcd for C19H19ClN2O2:
C, 66.57; H, 5.59; N, 8.17; found: C, 66.50; H, 5.51; N, 8.14%. LC-MS:
343.29, 345.32 [M+1].
These compounds were synthesised according to the literature
procedure.17
5,6-Dimethyl-2-(4-methylbenzyl)-1H-benzimidazole (2a): Yield 2.22 g
(89%); m.p. 200–201°C (lit.18 200 °C).
5,6-Dimethyl-2-(4-fluorobenzyl)-1H-benzimidazole
(2b):
Cas
1
No:1176128-02-1; yield 1.93 g (76%); m.p. 178–179 °C; H NMR
(DMSO-d6, 400 MHz): 4.09 (s, 2H), 7.109–7.13 (m, 2H), 7.21 (s, 2H),
7.30–7.33 (m, 2H), 11.97 (s, 1H). Anal calcd for C16H15FN2: C, 75.57; H,
5.95; N, 11.02; found: C, 75.48; H, 5.90; N, 10.97%. LC-MS:255.23,
256.21 [M+1].
Methyl
[5,6-dimethyl-2-(4-methoxybenzyl)-1H-benzimidazol-1-yl]
acetate (3d): Yield 2.84 g (84%); m.p. 121–122 °C; 1H NMR (DMSO-d6,
400 MHz): 2.25 (s, 6H), 3.51 (s, 3H), 3.74 (s, 3H), 4.13 (s, 2H), 5.03 (s,
2H), 7.81 (d, J=8.0, 2H), 7.12 (d, J=8.0, 2H), 7.18 (s, 1H), 7.36 (s, 1H).
13C NMR (DMSO-d6, 100 MHz): 20.26, 20.49 (CH3), 32.41 (CH2),
44.75 (NCH2), 52.57, 55.48 (OCH3), 110.54, 114.23, 119.17, 128.87
(2C), 130.17, 130.23, 130.84 (2C), 134.65, 141.13, 153.52 (ArC), 158.37
(C=N), 168.77 (C=O). Anal calcd for C20H22N2O3: C, 70.99; H, 6.55;
N, 8.28; found: C, 70.93; H, 6.48; N, 8.23%. LC-MS: 339.37 [M+1].
Methyl [5,6-dimethyl-2-(4-nitrobenzyl)-1H-benzimidazol-1-yl]acetate
5,6-Dimethyl-2-(4-chlorobenzyl)-1H-benzimidazole (2c): Yield 2.22 g
(89%); m.p. 200–201°C (lit.19 199–200°C).
5,6-Dimethyl-2-(4-methoxybenzyl)-1H-benzimidazole (2d): Cas
1
No:1175987-50-4; yield 2.21 g (83%); m.p. 195–196 °C; H NMR
(DMSO-d6, 400 MHz):4.04 (s, 2H), 6.85 (d, J=8.8, 2H), 7.19–7.22 (m,
4H). Anal calcd for C17H18N2O: C, 76.66; H, 6.81; N, 10.52; found: C,
76.61; H, 6.74; N, 10.47%. LC-MS:267.34 [M+1].
5,6-Dimethyl-2-(4-nitrobenzyl)-1H-benzimidazole (2e): Yield 2.13 g
(76%); m.p. 210–211 °C (lit.20 208–210 °C).
1
(3e): Yield 2.44 g (69%); m.p. 148–149 °C; H NMR (DMSO-d6, 400
MHz): 2.24 (s, 6H), 3.56 (s, 3H), 4.36 (s, 2H), 5.12 (s, 2H), 7.21 (s,
1H), 7.35 (s, 1H), 7.54 (d, J=8.0, 2H), 8.17 (d, J=8.0, 2H). 13C NMR
(DMSO-d6, 100 MHz): 20.25, 20.35 (CH3), 32.78 (CH2), 44.76 (NCH2),
52.64 (OCH3), 110.62, 119.26, 123.85 (2C), 130.45, 130.73 (2C), 131.78,
134.49, 141.11, 145.35, 146.72 (ArC), 152.19 (C=N), 168.85 (C=O).
Anal calcd for C19H19N3O4: C, 64.58; H, 5.42; N, 11.89; found: C, 64.52;
H, 5.37; N, 11.83%. LC-MS: 354.35 [M+1].
5,6-Dimethyl-2-(4-bromobenzyl)-1H-benzimidazole
(2f):
Cas
1
No:1272924-42-1; yield 2.46 g (78%); m.p. 215–216 °C; H NMR
(DMSO-d6, 400 MHz):4.08 (s, 2H), 7.21–7.25 (m, 4H), 7.46 (d, J=8.4,
2H), 12.00 (s, 1H). Anal calcd for C16H15BrN2: C, 60.97; H, 4.80; N,
8.89; found: C, 60.92; H, 4.72; N, 8.83. LC-MS:315.22, 317.25 [M+1].
Synthesis of 3a–f
Methyl [5,6-dimethyl-2-(4-bromobenzyl)-1H-benzimidazol-1-yl]acetate
1
A mixture of compounds 2a–f (0.01 mol) in acetone (25 mL) and
dry K2CO3 (0.025 mol) was stirred for 10 min and then, methyl
bromoacetate (0.011 mol) was added. The mixture was stirred at room
(3f): Yield 2.94 g (76%); m.p. 139–140 °C; H NMR (DMSO-d6, 400
MHz): 1H NMR (DMSO-d6, 400 MHz): 2.26 (s, 6H), 3.51 (s, 3H), 4.16 (s,
2H), 5.09 (s, 2H), 7.18–7.21 (m, 3H), 7.32 (s, 1H), 7.45 (d, J=8.0, 2H).

JOURNAL OF CHEMICAL RESEARCH 2015 647
13C NMR (DMSO-d6, 100 MHz):20.26, 20.49 (CH3), 32.49 (CH2),
44.74 (NCH2), 52.58 (OCH3), 110.60, 119.21, 120.10, 130.32, 131.02,
131.57 (2C), 131.63 (2C), 134.57, 136.58, 141.09 (ArC), 152.78 (C=N),
168.78 (C=O). Anal calcd for C19H19BrN2O2: C, 58.93; H, 4.95;
N, 7.23; found: C, 58.85; H, 4.90; N, 7.18%. LC-MS: 387.32, 389.28
[M+1].
153.14 (C=N), 166.45 (C=O). Anal calcd for C18H19BrN4O: C, 55.82;
H, 4.95; N, 14.47; found: C, 55.73; H, 4.88; N, 14.41%. LC-MS: 387.32,
389.28 [M+1].
Synthesis of 2-oxo-2H-chromene-3-carboxylic acid (5)
Synthesised according to the literature procedure.21 Yield 1.63 g (86%);
m.p. 190–191 °C (lit.21 190 °C).
Synthesis of 4a–f
Synthesis of 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-one (6)
Hydrazine monohydrate (0.05 mol) was added to the solution of
compounds 3a–f (0.01 mol) in ethanol (15 mL). The mixture was
stirred for 5 hours at room temperature. After the reaction was
completed (monitored by TLC, ethyl acetate/hexane, 3/1), the
precipitated product was filtered off, washed with cold ethanol and
recrystallized from ethanol.
Synthesised according to the literature procedure.22 Yield 2.21 g
(76%); m.p. 185–186 °C (lit.22 186–187 °C).
Synthesis of 7a–f
A solution of compounds 4a–f (0.01 mol) in ethanol (15 mL) and
compound 6 (0.012 mol) was placed in a round-bottomed flask. The
mixture was refluxed for 6 h. After the completion of the reaction
(monitored by TLC, ethyl acetate:hexane: 3/1), the mixture was cooled
to room temperature and a solid appeared. This crude product was
filtered and washed with ethanol to obtain the pure product.
2-(4-Methylbenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7a): Yield 3.06 g
(62%); m.p. 215–216 °C; 1H NMR (DMSO-d6, 400 MHz): 2.23 (s, 3H),
2.27 (s, 3H), 2.29 (s, 3H), 4.16 (s, 2H), 4.91 (s, 2H), 7.07 (d, J=8.0, 2H),
7.14 (d, J=8.0, 2H), 7.24 (s, 1H), 7.31 (s, 1H), 7.43 (t, J=7.2, 1H), 7.48
(d, J=8.8, 1H), 7.75 (t, J=8.0, 1H), 7.99 (dd, J=8.0, J=1.6, 1H), 8.98
(s, 1H), 10.63 (s, 1H), 11.22 (s, 1H). 13C NMR (DMSO-d6, 100 MHz):
20.28, 20.55, 21.06 (CH3), 32.98 (CH2), 44.50 (NCH2), 110.63, 116.70,
118.31, 119.15, 125.69, 129.14, 129.43, 130.06, 130.71, 130.83, 134.22,
134.71, 134.93, 135.95, 141.21 (ArC), 148.59 (CHcoumarin-C4), 153.64
(C=N), 154.40 (Ccoumarin-C3), 159.21 (C=Ocoumarin-C2), 160.29, 164.74
(C=O). Anal calcd for C29H26N4O4: C, 70.43; H, 5.30; N, 11.33; found:
C, 70.35; H, 5.26; N, 11.26%. LC-MS: 495.23 [M+1].
2-[5,6-Dimethyl-2- (4-methylbenzyl)-1H-benzimidazol-1-yl]
acetohydrazide (4a): Yield 2.32 g (72%); m.p. 200–201 °C; H NMR
1
(DMSO-d6, 400 MHz):2.24 (s, 3H), 2.27 (s, 6H), 4.14 (s, 2H), 4.29
(s, 2H), 4.66 (s, 2H), 7.07–7.15 (m, 5H), 7.29 (s, 1H), 9.42 (s, 1H).
13C NMR (DMSO-d6, 100 MHz): 20.28, 20.54, 21.06 (CH3), 32.98
(CH2), 44.82 (NCH2), 110.54, 119.13, 129.03 (2C), 129.10 (2C), 129.41,
130.55, 134.34, 134.59, 135.90, 141.25 (ArC), 153.66 (C=N), 166.47
(C=O). Anal calcd for C19H22N4O: C, 70.78; H, 6.88; N, 17.38; found:
C, 70.71; H, 6.82; N, 17.33%. LC-MS: 323.34 [M+1].
2-[5,6-Dimethyl-2- (4-fluorobenzyl)-1H-benzimidazol-1-yl]
acetohydrazide (4b): Yield 2.54
g (78%); m.p. 220–221 °C;
1H NMR (DMSO-d6, 400 MHz): 2.26 (s, 3H), 2.27 (s, 3H), 4.19
(s, 4H, CH2 + NH2), 4.72 (s, 2H), 7.12–7.38 (s, 6H), 9.47 (s, 1H).
13C NMR (DMSO-d6, 100 MHz): 20.28, 20.54 (CH3), 32.42 (CH2),
44.85 (NCH2), 110.56, 115.37 (2C), 119.16, 130.06, 130.66, 131.16 (2C),
133.63, 134.53, 141.26 (ArC), 153.48 (C=N), 161.44 (C-F, JC-F=240.5
Hz), 166.48 (C=O). Anal calcd for C18H19FN4O: C, 66.24; H, 5.87; N,
17.17; found: C, 66.18; H, 5.81; N, 17.13%. LC-MS: 327.42 [M+1].
2-[5,6-Dimethyl-2- (4-chlorobenzyl)-1H-benzimidazol-1-yl]
2-(4-Fluorobenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7b): Yield 2.64 g
1
1
acetohydrazide (4c): Yield 2.53 g (74%); m.p. 190–191 °C; H NMR
(53%); m.p. 273–274 °C; H NMR (DMSO-d6, 400 MHz): 2.23 (s,
(DMSO-d6, 400 MHz): 2.28 (s, 3H), 2.29 (s, 3H), 4.19 (s, 2H), 4.24
(s, 2H), 4.75 (s, 2H), 7.11 (s, 1H), 7.21–7.38 (m, 5H), 9.44 (s, 1H).
13C NMR (DMSO-d6, 100 MHz): 20.28, 20.25 (CH3), 32.55 (CH2),
44.86 (NCH2), 110.57, 119.16, 128.70 (2C), 130.08, 130.69, 131.19 (2C),
131.25, 134.51, 136.57, 141.22 (ArC), 153.20 (C=N), 166.45 (C=O).
Anal calcd for C18H19ClN4O: C, 63.06; H, 5.59; N, 16.34; found: C,
63.01; H, 5.51; N, 16.26%. LC-MS: 343.40, 345.36 [M+1].
3H), 2.29 (s, 3H), 4.21 (s, 2H), 4.96 (s, 2H), 7.06–7.13 (m, 2H), 7.25 (s,
1H), 7.28–7.7.35 (m, 3H), 7.43 (t, J=8.0, 1H), 7.49 (d, J=8.0, 1H), 7.75
(t, J=8.0, 1H), 8.00 (d, J=8.0, 1H), 8.90 (s, 1H), 10.65 (s, 1H), 11.25
(s, 1H). 13C NMR (DMSO-d6, 100 MHz): 20.28, 20.56 (CH3), 32.40
(CH2), 44.52 (NCH2), 110.64, 115.40, 115.62, 118.35, 118.75, 119.19,
125.70, 130.13, 130.78, 131.18, 131.26, 133.55, 134.65, 134.93, 141.22
(ArC), 148.58 (CHcoumarin-C4), 153.45 (C=N), 154.41 (Ccoumarin-C3), 159.22
(C=Ocoumarin-C2), 160.28 (C=O), 161.46 (C-F, JC-F=241.2 Hz), 164.75
(C=O). Anal calcd for C28H23FN4O4: C, 67.46; H, 4.65; N, 11.24;
found: C, 67.40; H, 4.57; N, 11.16%. LC-MS: 499.20, 500.19 [M+1].
2-(4-Chlorobenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7c): Yield 3.16 g
2-[5,6-Dimethyl-2-(4-methoxybenzyl)-1H-benzimidazol-1-yl]
1
acetohydrazide (4d): Yield 2.47 g (73%); m.p. 179–180 °C; H NMR
(DMSO-d6, 400 MHz): 2.13 (s, 3H), 2.14 (s, 3H), 3.75 (s, 3H), 4.03 (s,
2H), 4.37 (s, 2H), 4.65 (s, 2H), 6.75–6.89 (m, 2H), 7.11–7.23 (m, 3H),
7.31 (s, 1H), 9.41 (s, 1H). 13C NMR (DMSO-d6, 100 MHz): 20.29,
20.54 (CH3), 32.51 (CH2), 44.81 (NCH2), 55.46 (OCH3), 110.52, 114.26
(2C), 119.12, 129.27, 129.94, 130.25 (2C), 130.53, 134.59, 144.24
(ArC), 153.86 (C=N), 158.35 (C-O, ArC), 166.49 (C=O). Anal calcd
for C19H22N4O2: C, 67.44; H, 6.55; N, 16.56; found: C, 67.37; H, 6.48; N,
16.51%. LC-MS: 339.46 [M+1].
1
(61%); m.p. 261–261 °C; H NMR (DMSO-d6, 400 MHz): 2.26 (s,
3H), 2.29 (s, 3H), 4.22 (s, 2H), 4.95 (s, 2H), 7.26 (s, 1H), 7.27–7.33
(m, 5H), 7.44 (t, J=8.0, 1H), 7.50 (d, J=8.0, 1H), 7.75 (t, J=8.0, 1H),
8.00 (d, J=8.0, 1H), 8.90 (s, 1H), 10.66 (s, 1H), 11.26 (s, 1H). 13C NMR
(DMSO-d6, 100 MHz): 20.29, 20.56 (CH3), 32.55 (CH2), 44.53
(NCH2), 110.66, 116.71, 118.34, 118.75, 119.19, 125.70, 128.73 (2C),
130.17, 130.85, 131.27 (2C), 131.61, 134.65, 134.93, 136.45, 141.20
(ArC), 148.58 (CHcoumarin-C4), 153.16 (C=N), 154.41 (Ccoumarin-C3),
159.17 (C=Ocoumarin-C2), 160.28 (C=O), 164.70 (C=O). Anal calcd for
C28H23ClN4O4: C, 65.31; H, 4.50; N, 10.88; found: C, 65.23; H, 4.41; N,
10.82%. LC-MS: 515.17, 517.16 [M+1].
2-[5,6-Dimethyl-2- (4-nitrobenzyl) -1H-benzimidazol-1-yl]
acetohydrazide (4e): Yield 2.50
g (71%); m.p. 253–254 °C;
1H NMR (DMSO-d6, 400 MHz): 2.11 (s, 3H), 2.13 (s, 3H), 4.23 (s, 4H,
CH2+NH2), 4.78 (s, 2H), 7.18 (s, 1H), 7.25 (s, 1H), 7.56 (d, J=8.0, 2H),
8.16 (d, J=8.0, 2H), 9.42 (s ,1H). 13C NMR (DMSO-d6, 100 MHz):
20.28, 20.55 (CH3), 32.99 (CH2), 44.90 (NCH2), 110.58, 119.21, 123.84
(2C), 130.22, 130.83 (2C), 130.87, 134.45, 141.21, 145.76, 146.71 (ArC),
152.56 (C=N), 166.40 (C=O). Anal calcd for C18H19N5O3: C, 61.18; H,
5.42; N, 19.82; found: C, 61.09; H, 5.37; N, 19.74%. LC-MS: 354.42,
355.33 [M+1].
2-(4-Methoxybenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7d): Yield 2.96 g
1
(2.96%); m.p. 228–229 °C; H NMR (DMSO-d6, 400 MHz): 2.26
(s, 3H), 2.29 (s, 3H), 3.69 (s, 3H), 4.13 (s, 2H), 4.91 (s, 2H), 6.83 (dd,
J=6.8, J=2.0, 2H), 7.20 (d, J=8.2, 2H), 7.23 (s, 1H), 7.31 (s, 1H),
7.46 (t, J=8.2, 1H), 7.50 (d, J=8.0, 1H), 7.76 (t, J=8.2, 1H), 8.00 (dd,
J=6.8, J=2.0, 1H), 8.90 (s, 1H), 10.64 (s, 1H), 11.22 (s, 1H). 13C NMR
(DMSO-d6, 100 MHz): 20.29, 20.56 (CH3), 32.51 (CH2), 44.48
(NCH2), 55.44 (OCH3), 110.62, 114.28 (2C), 116.71, 118.35, 118.75,
119.15, 125.70, 129.15, 130.03, 130.29 (2C), 130.67, 130.84, 134.72,
134.93, 141.23 (ArC), 148.57 (CHcoumarin-C4), 153.82 (C=N), 154.41
2-[5,6-Dimethyl-2- (4-bromobenzyl)-1H-benzimidazol-1-yl]
1
acetohydrazide (4f): Yield 3.09 g (80%); m.p. 192–193 °C; H NMR
(DMSO-d6, 400 MHz): 2.23 (s, 3H), 2.27 (s, 3H), 4.18 (s, 2H), 4.34 (s,
2H), 4.71 (s, 2H), 7.15 (s, 1H), 7. 22 (d, J=7.8, 2H), 7.21 (s, 1H), 7.45
(d, J=7.8, 2H), 9.42 (s, 1H). 13C NMR (DMSO-d6, 100 MHz): 20.28,
20.56 (CH3), 32.63 (CH2), 44.86 (NCH2), 110.56, 119.17, 120.04,
130.09, 131.58, 131.63 (2C), 131.66 (2C), 134.51, 137.00, 141.21 (ArC),

648 JOURNAL OF CHEMICAL RESEARCH 2015
(Ccoumarin-C3), 158.37 (ArC, C-O), 159.18 (C=Ocoumarin-C2), 160.29 (C=O),
164.74 (C=O). Anal calcd for C29H26N4O5: C, 68.22; H, 5.13; N, 10.97;
found: C, 68.15; H, 5.06; N, 10.91%. LC-MS: 511.22, 512.21 [M+1].
2-(4-Nitrobenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7e): Yield 2.57 g
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3H), 2.29 (s, 3H), 4.39 (s, 2H), 5.01 (s, 2H), 7.28 (s, 1H), 7.31 (s, 1H),
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10.64 (s, 1H), 11.28 (s, 1H). 13C NMR (DMSO-d6, 100 MHz): 20.28,
20.58 (CH3), 30.01 (CH2), 44.57 (NCH2), 110.70, 116.71, 118.27, 118.74,
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H, 4.36; N, 13.26%. LC-MS: 526.19 [M+1].
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2-(4-Bromobenzyl)-5,6-dimethyl-N’-[(2-oxo-2H-chromen-3-yl)
carbonyl]-1H-benzimidazole-1-carbohydrazide (7f): Yield 3.74 g
1
(67%); m.p. 260–261 °C; H NMR (DMSO-d6, 400 MHz): 2.26 (s,
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8.90 (s, 1H), 10.66 (s, 1H), 11.26 (s, 1H). 13C NMR (DMSO-d6, 100
MHz): 20.29, 20.58 (CH3), 32.62 (CH2), 44.53 (NCH2), 110.65, 116.70,
118.334, 118.75, 119.19, 120.10, 125.70, 130.17, 130.85, 131.66, 134.66,
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This work was supported by The Scientific and Technological
Research Council of Turkey (TUB TAK, project no. 115Z047)
and Recep Tayyip Erdogan University Scientific Research
Project Unit (BAP, project no. 2014.102.02.05). The authors
thank TUBITAK and Recep Tayyip Erdogan University for
their support.
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Received 10 August 2015; accepted 3 October 2015
Paper 1503537 doi: 10.3184/174751915X14449030550960
Published online: 1 November 2015