Microwave-assisted synthesis of some 5(6)-nitro-1H-benzimidazoles and their hydrazide derivatives

Article abstract of DOI:10.4314/bcse.v27i2.11

A series of 5(6)-nitro-1H-benzimidazole and their hydrazide derivatives were synthesized starting from iminoester hydrochloride and 4-nitro-o- phenylenediamine under microwave irradiation. The structure of all synthesized compounds was confirmed by IR,

Full text of DOI:10.4314/bcse.v27i2.11

Bull. Chem. Soc. Ethiop. 2013, 27(2), 265-271.
Printed in Ethiopia
ISSN 1011-3924
 2013 Chemical Society of Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v27i2.11
MICROWAVE-ASSISTED SYNTHESIS OF SOME 5(6)-NITRO-1H-
BENZIMIDAZOLES AND THEIR HYDRAZIDE DERIVATIVES
Fatih Yılmaz1, Emre Menteşe1*, Nesrin Karaali1 and Bahittin Kahveci2
1 Department of Chemistry, Faculty of Arts and Sciences, Recep Tayyip Erdoğan University,
53100, Rize, Turkey
2Department of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical
University, Trabzon, Turkey
(Received October 17, 2012; revised February 8, 2013)
ABSTRACT. A series of 5(6)-nitro-1H-benzimidazole and their hydrazide derivatives were synthesized starting
from iminoester hydrochloride and 4-nitro-o-phenylenediamine under microwave irradiation. The structure of all
synthesized compounds was confirmed by IR, 1H-NMR, 13C-NMR, ESI-MS spectroscopy and elemental analysis.
KEY WORDS: Benzimidazole, Iminoester hydrochloride, Microwave irradiation, Hydrazine hydrate
INTRODUCTION
Benzimidazoles are crucial structures for medicinal chemistry because they show important
biological and pharmaceutical activities including anti-cancer, anti-microbial, anti-fungal, anti-
ulcer and anti-viral [1, 2]. Furthermore, various kinds of benzimidazole derivatives are found in
diverse array of compounds, including biologically and therapeutically active agents [3], natural
products [4]. Therefore, these compounds have been attracted attention of synthetic organic
chemist.
A number of synthetic methods have been developed in recent years to bring out new
reagents for the synthesis of 2-substitued benzimidazoles [5-9]. A major drawback of these
methods is the poor yields, use of expensive reagents and long reaction time. Moreover,
economical and environmental conditions are forcing the chemical community to find more
efficient ways for performing chemical reactions [10]. The use of microwave irradiation in
chemical reactions leads to enhanced reaction rates, higher yields of products, easier work-up
and, sometimes, to selective conversions with several advantages of the eco-friendly approach
in the framework of green chemistry [11]. Consequently, this protocol should be welcome in
these environmentally conscious days.
Because of these reasons, microwave-assisted synthesis of benzimidazoles has been come
into prominence and many benzimidazole derivatives have been gained in literature. In this
study, we wish to report the synthesis of 5-nitro-1H-benzimidazoles and their hydrazide
derivatives starting from iminoester hydrochlorides, which can be easily obtained, under
microwave irradiation and with conventional heating.
RESULTS AND DISCUSSION
Synthesis of the compounds 4(a-d) has been carried out as depicted in Scheme 1.
Ethylimidobenzylacetate hydrochlorides 1(a-d) was prepared according to the Pinner method
[12-14]. To synthesize benzimidazole compounds, secondly, there has been developed a simple
method using 4-nitro-o-phenylenediamine and ethylimidobenzylacetate hydrochlorides 1(a-d)
__________
*Corresponding author. E-mail: emre.mentese@erdogan.edu.tr

266
Emre Menteşe et al.
with microwave irradiation and classical method, then, 5(6)-nitro-1H-benzimidazoles 2(a-d)
have been obtained. Ethyl [2-benzyl-5(6)-nitro-1H-benzimidazol-1-yl]acetates
3(a-d) have been prepared with treatment of compounds 2(a-d) and ethyl bromoacetate in
acetone. Finally, compounds 3(a-d) has been reacted with hydrazine monohydrate in ethanol to
synthesize 2-[5(6)-nitro-2-benzyl)-1H-benzimidazol-1-yl]acetohydrazide 4(a-d). All reactions
have been carried out with conventional heating and under microwave irradiation and results
were compared (Table 1.).
NH
2
N
CH2CN
+
NH.HCl
O2
N
O
N
NH
2
2
Diethyl Ether
+
C H OH
N
H
HCl(g)
2
5
0-5 °C
MWI or Conventional
Heating
OC
H
5
2
R
R
R
2 a-d
1 a-d
BrCH2COOC2H5, K2CO3
Acetone
MWI or Conventional
Heating
N
N
N
N
O
N
2
R: a:
b:
c:
-CH3(m),
-CH3(o),
O2
N
NH2NH2.H2O, Ethanol
-Cl(o), d: -Cl(m)
MWI or Conventional
Heating
H2NHN
R
H5C2
O
R
O
O
4 a-d
3 a-d
Scheme 1. Synthetic route for compounds 2a-d, 3a-d and 4a-d.
Table 1. Comparation of yields and reaction times of classical and microwave condition.
Classical conditions
Microwave conditions
Temperature (°C) Time (min)
Yielda ( % )
Yielda (%)
Compound
Time (h)
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
6
6
6
71 (60b [18])
60
60
60
60
90
90
90
90
120
120
120
120
10
10
10
10
15
15
15
15
10
10
10
10
87
91
93
88
96
92
95
90
79
70
71
65
79 ( 65b [18])
80
72
86
89
79
74
50
45
54
40
6
10
10
10
10
6
6
6
6
aisolated yield, bisolated yield for ref. 18.
The IR spectrum of all compounds shows characteristic absorptions bands at about 1510 and
1315 cm-1 for –NO2 and 1620 cm-1 for C=N. The C=O band is at about 1735 cm-1 and 1645 cm-1
for compounds 3(a-d) and 4(a-d), respectively. Also, compounds 4(a-d) have new NH and NH2
signals between 3300-3296 cm-1 because of hydrazide formation.
1H-NMR spectra of each compound shows compatible signals with proposed structures.
N-H signals are shown at about 13.00 ppm for compounds 2(a-d) and 9.75 ppm for compounds
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Microwave-assisted synthesis of some 5(6)-nitro-1H-benzimidazoles and their hydrazides 267
for compounds 4(a-d). With the alkylation reaction of compounds 2(a-d), -NH signals have
been left and new signals belonging to –NCH2COOEt have been shown for compounds 3(a-d).
With the conversion of compounds 3(a-d) to their hydrazide derivatives 4(a-d), the OCH2 and
–OCH2CH3 signals disappeared and new –NH and –NH2 signals were shown.
13C-NMR spectra of each compounds showed compatible signals with proposed structures.
C=O signals are shown at about 175 and 168 ppm for compounds 3(a-d) and 4(a-d),
respectively. The signals belonging to –OCH2CH3 group for compounds 3(a-d) are at the related
chemical values. No –OCH2CH3 signals has been shown for compounds 4(a-d). That proves the
hydrazide formation. In addition, all compounds gave stable M+1 ion peak and reasonable
elemental analysis data.
EXPERIMENTAL
All the chemicals were supplied from Merck, Aldrich and Fluka. Melting points were
determined on capillary tubes on a Büchi oil heated melting point apparatus and uncorrected.
1H- and 13C-NMR spectra were performed on Varian-Mercury 200 MHz spectrophotometer in
DMSO-d6 using TMS as internal. The IR spectra were recorded on a Perkin-Elmer 100 FTIR
spectrophotometer as KBr pellets. The elemental compositions were determined on a Carlo Erba
1106 CHN analyzer; the experimental values were in agreement ( 0.4%) with calculated ones.
Mass spectra were recorded on Thermo Scientific Quantum Access max LC-MS
spectrophotometer. A mono-mode CEM-Discover microwave was used to carry out microwave
reactions in 30 mL microwave process vials with temperature control by infrared detection
temperature sensor. All reactions were monitored by TLC using precoated aluminum sheets
(silica gel 60 F 2.54 0.2 mm thickness).
Synthesis of compounds 2a-d
Conventional method. A mixture of 4-nitro-o-phenylenediamine (0.01 mol) and corresponding
iminoester hydrochloride 1(a-d) (0.013 mol) in methanol (30 mL) were stirred at room
temperature for 4 h. Then the mixture was refluxed for 2 h. After the reaction was completed,
monitored by TLC (EtAc:hexane, 3:1), the mixture was cooled down to room temperature, the
product was precipitated with addition of water. The obtained product was filtered, dried and
recrystallized from ethanol-water (1:1).
Microwave method. 4-Nitro-o-phenylenediamine (0.01 mol) and corresponding iminoester
hydrochloride (1a-d) (0.013 mol) in methanol (10 mL) were taken in a closed vessel. Then, it
was irradiated in microwave at 60 °C and 10 min (hold time) at 300 Watt maximum power.
After the reaction was completed (monitored as stated above), the mixture was cooled down to
room temperature and taken in a beaker. The product was precipitated by addition of water and
purification methods mentioned above were applied.
2-(2-Methylbenzyl)-5(6)-nitro-1H-benzimidazole (2a). m.p.: 168-170 °C (165-166 °C [18]), IR
1
(KBr): 3100 (NH), 3023 (Ar-H), 1625 (C=N), 1513, 1322 (NO2) cm-1. H-NMR (200 MHz,
DMSO-d6) δ: 12.95 (NH), 8.43 (s, 1H, Ar-H), 8.12 (d, 1H, J = 8.3 Hz, Ar-H,), 8.03 (d, 1H, J =
8.3, Ar-H), 7.43-7.02 (m, 4H, Ar-H), 4.23 (2H, t, J = 7.3, CH2), 2.27 (3H, d, J = 7.3, CH3). 13C-
NMR (50 MHz, DMSO-d6) δ: 157.2 (C=N), 145.3 (C), 143.1 (C), 140.9 (C), 136.7 (C), 133.1
(C), 130.6 (CH), 128.5 (2CH), 126.1 (CH), 124.3 (2CH), 122.9 (CH), 32.7 (CH2), 19.5 (CH3).
ESI-MS m/z (rel. int.) 268 [M+1] (100), 253 (37), 163 (51).
2-(3-Methylbenzyl)-5(6)-nitro-1H-benzimidazole (2b). m.p.: 170-171 °C (166-167 °C [18]),
1
IR (KBr): 3094 (NH), 3009 (Ar-H), 1623 (C=N), 1513, 1320 (NO2) cm-1. H-NMR (200 MHz,
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DMSO-d6) δ: 12.78 (NH), 8.49 (s, 1H, Ar-H), 8.08 (d, 1H, J = 8.1 Hz, Ar-H,), 7.92 (d, 1H, J =
8.1, Ar-H), 7.40-6.92 (m, 4H, Ar-H), 4.23 (2H, s, CH2), 2.27 (3H, s, CH3). 13C-NMR (50 MHz,
DMSO-d6) δ: 159.2 (C=N), 149.3 (C), 141.1 (2C), 136.7 (C), 133.1 (C), 131.6 (CH), 128.5
(CH), 128.0 (CH), 125.1 (2CH), 123.0 (CH), 121.7 (CH), 34.1 (CH2), 20.3 (CH3). ESI-MS m/z
(rel. int.) 268 [M+1] (100), 253 (39), 163 (69).
2-(2-Chlorobenzyl)-5(6)-nitro-1H-benzimidazole (2c). m.p.: 203-204 °C, IR (KBr): 3114 (NH),
1
3018 (Ar-H), 1621 (C=N), 1515, 1327 (NO2) cm-1. H-NMR (200 MHz, DMSO-d6) δ: 13.05
(NH), 8.37 (s, 1H, Ar-H), 8.09 (d, 1H, J = 8.3 Hz, Ar-H), 7.90 (d, 1H, J = 8.3, Ar-H), 7.35-7.00
(m, 4H, Ar-H), 4.39 (2H, t, J = 7.3, CH2). 13C-NMR (50 MHz, DMSO-d6) δ: 155.1 (C=N),
149.2 (C), 145.2 (C), 141.9 (C), 136.7 (2C), 131.2 (CH), 129.5 (CH), 125.3 (2CH), 123.1 (CH),
120.9 (2CH), 36.7 (CH2). ESI-MS m/z (rel. int.) 290 [M+3] (35), 288 [M+1] (100), 177 (47),
163 (51). Anal. C 58.45%, H 3.50%, N 14.61 %, calcd. for C14H10ClN3O2, 58.41%, H 3.52%, N
14.64 %.
2-(3-Chlorobenzyl)-5(6)-nitro-1H-benzimidazole (2d). m.p.: 198-200 °C, IR (KBr): 3110 (NH),
1
3008 (Ar-H), 1629 (C=N), 1518, 1320 (NO2) cm-1. H-NMR (200 MHz, DMSO-d6) δ: 13.00
(NH), 8.30 (s, 1H, Ar-H), 8.04 (d, 1H, J = 8.5 Hz, Ar-H,), 7.99 (d, 1H, J = 8.5, Ar-H), 7.21-6.00
(m, 4H, Ar-H), 4.41 (2H, t, J = 7.3, CH2). 13C-NMR (50 MHz, DMSO-d6) δ: 153.2 (C=N),
148.1 (C), 145.9 (C), 146.0 (C), 138.7 (C), 136.2 (C), 135.1 (CH), 132.7 (CH), 129.3 (2CH),
125.1 (CH), 121.2 (CH), 199.1 (CH) 39.1 (CH2). ESI-MS m/z (rel. int.) 290 [M+3] (35), 288
[M+1] (100), 177 (42), 163 (69). Anal. C 58.45%, H 3.50%, N 14.61 %, calcd. for
C14H10ClN3O2, 58.43%, H 3.51%, N 14.59 %.
Synthesis of compounds 3a-d
Conventional method. A mixture of compound 2a-d (0.01 mol), ethyl bromoacetate (0.01 mol)
and dry K2CO3 (0.03 mol) in acetone (20 mL) were stirred in a room temperature for 10 h. After
the reaction was completed, monitored by TLC (EtAc:hexane, 4:1), the product was precipitated
by addition of water and was filtrated, dried and recrystallized from ethanol to afford the desired
product.
Microwave method. A solution of compound 2a-d (0.01 mol) in acetone (10 mL) was taken in a
closed vessel and dry K2CO3 (0.03 mol) was added. The mixture was irritated in microwave at
90 ºC, 5 min (hold time, 5 bar) at 300 Watt maximum power. Then, the mixture was cooled
down to room temperature and ethyl bromoacetate (0.01mol) was added. Again, it was
irradiated in microwave at 90 ºC and 10 min (hold time) at 300 Watt maximum power. After the
reaction was completed (monitored as stated above), the mixture was cooled, taken in a beaker
and the product was precipitated by addition of water. Purification methods mentioned above
were applied to yield the pure product.
Ethyl [2-(2-methylbenzyl)-5(6)-nitro-1H-benzimidazol-1-yl] acetate (3a). m.p.: 130-132 °C, IR
1
(KBr): 3019 (Ar-H), 1736 (C=O), 1620 (C=N), 1517, 1320 (NO2) cm-1. H-NMR (200 MHz,
DMSO-d6) δ: 8.50 (s, 1H, Ar-H), 8.22 (d, 1H, J = 8.0 Hz, Ar-H,), 8.10 (d, 1H, J = 8.0, Ar-H),
7.73-7.29 (m, 4H, Ar-H), 5.37 (2H, s, N-CH2), 4.23 (2H, q, J = 7.3, CH2), 4.00 (2H, q, J = 7.2
Hz, OCH2), 2.27 (3H, t, J = 7.3, CH3), 1.10 (3H, t, J = 7.2, CH3). 13C-NMR(50 MHz, DMSO-
d6) δ: 170.3 (C=O), 157.6 (C=N), 148.2 (C), 142.1 (C), 140.0 (C), 136.7 (2C), 132.6 (CH),
128.5 (CH), 127.7 (CH), 126.1 (CH), 124.3 (CH), 123.2 (CH), 122.9 (CH), 47.2 (CH2), 32.7
(CH2), 19.5 (CH3), 15.9 (CH3) .ESI-MS m/z (rel. int.) 354 [M+1] (100), 267 (65), 263 (34), 163
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Microwave-assisted synthesis of some 5(6)-nitro-1H-benzimidazoles and their hydrazides 269
(39). Anal. C 64.58%, H 5.42%, N 11.89 %, calcd. for C19H19N3O4, C 64.55%, H 5.43%, N
11.91 %.
Ethyl [2-(3-methylbenzyl)-5(6)-nitro-1H-benzimidazol-1-yl] acetate (3b). m.p.: 140-141 °C, IR
1
(KBr): 3003 (Ar-H), 1740 (C=O), 1622 (C=N), 1510, 1329 (NO2) cm-1. H-NMR (200 MHz,
DMSO-d6) δ: 8.61 (s, 1H, Ar-H), 8.23 (d, 1H, J = 8.1 Hz, Ar-H,), 8.10 (d, 1H, J = 8.1, Ar-H),
7.70-7.27 (m, 4H, Ar-H), 5.31 (2H, s, N-CH2), 4.20 (2H, s, CH2), 4.11 (2H, q, J = 7.0 Hz,
OCH2), 2.25 (3H, s, CH3), 1.10 (3H, t, J = 7.0 Hz, CH3). 13C-NMR(50 MHz, DMSO-d6) δ:
172.1 (C=O), 158.2 (C=N), 147.1 (C), 142.8 (C), 140.5 (C), 139.1 (2C), 135.2 (CH), 129.5
(CH), 128.1 (CH), 125.2 (CH), 123.1 (CH), 120.1 (CH), 118.2 (CH), 45.2 (CH2), 36.7 (CH2),
19.5 (CH3), 14.9 (CH3). ESI-MS m/z (rel. int.) 354 [M+1] (100), 267 (55), 263 (44), 163 (43).
Anal. C 64.58%, H 5.42%, N 11.89 %, calcd. for C19H19N3O4, C 64.57%, H 5.45%, N 11.89 %.
Ethyl [2-(2-chlorobenzyl)-5(6)-nitro-1H-benzimidazol-1-yl] acetate (3c). m.p.: 125-127 °C, IR
1
(KBr): 3011 (Ar-H), 1742 (C=O), 1624 (C=N), 1511, 1319 (NO2) cm-1. H-NMR (200 MHz,
DMSO-d6) δ: 8.60 (s, 1H, Ar-H), 8.29 (d, 1H, J = 8.2 Hz, Ar-H,), 8.10 (d, 1H, J = 8.2, Ar-H),
7.73-7.17 (m, 4H, Ar-H), 5.22 (2H, s, N-CH2), 4.22 (2H, s, CH2), 4.16 (2H, q, J = 7.0 Hz,
OCH2), 1.19 (3H, t, J = 7.0 Hz, CH3). 13C-NMR(50 MHz, DMSO-d6) δ: 175.2 (C=O), 159.2
(C=N), 145.9 (C), 143.1 (C), 141.8 (C), 138.1 (C), 136.4 (C), 134.7 (CH), 131.5 (CH), 129.1
(CH), 125.2 (CH), 123.1 (CH), 120.1 (CH), 118.2 (CH), 45.2 (CH2), 36.7 (CH2), 14.9 (CH3).
ESI-MS m/z (rel. int.) 376 [M+3] (35), 374 [M+1] (100), 339 (32), 290 (13), 292 (40), 288(23),
267 (55), 163 (31). Anal. C 57.84%, H 4.31%, N 11.24 %, calcd. for C18H16ClN3O4, C 57.87%,
H 4.33%, N 11.26 %.
Ethyl [2-(3-chlorobenzyl)-5(6)-nitro-1H-benzimidazol-1-yl] acetate (3d). m.p.: 115-116 °C, IR
1
(KBr): 3010 (Ar-H), 1745 (C=O), 1622 (C=N), 1513, 1318 (NO2) cm-1. H-NMR (200 MHz,
DMSO-d6) δ: 8.63 (s, 1H, Ar-H), 8.40 (d, 1H, J = 8.1 Hz, Ar-H,), 8.17 (d, 1H, J = 8.1, Ar-H),
7.73-7.17 (m, 4H, Ar-H), 5.40 (2H, s, N-CH2), 4.39 (2H, s, CH2), 4.19 (2H, q, J = 7.1 Hz,
OCH2), 1.28 (3H, t, J =7.1 Hz, CH3). 13C-NMR(50 MHz, DMSO-d6) δ: 176.1 (C=O), 158.9
(C=N), 147.7 (C), 145.1 (C), 143.8 (C), 139.9 (C), 137.8 (C), 136.2 (CH), 133.8 (CH), 130.0
(CH), 127.9 (CH), 124.8 (CH), 122.5 (CH), 119.9 (CH), 44.7 (CH2), 38.0 (CH2), 15.6 (CH3).
ESI-MS m/z (rel. int.) 376 [M+3] (35), 374 [M+1] (100), 339 (40), 290 (20), 292 (58), 288 (36)
267 (55), 163 (31). Anal. C 57.84%, H 4.31%, N 11.24 %, calcd. for C18H16ClN3O4, C 57.87%,
H 4.33%, N 11.26 %.
Synthesis of 2-(2-alkyl/aryl-5(6)-nitro-1H-benzimidazol-1-il)acetohydrazide (4a-d)
Conventional method. A mixture of 3a-d (0.01 mol) and hydrazine monohydrate (0.02 mol) in
ethanol (30 mL) was refluxed for 6 h. After the reaction was completed, monitored by TLC
(ethyl acetate:hexane, 3:1), the mixture was cooled down to room temperature and a white solid
appeared. This crude product was filtrated, dried and recrystallized from ethanol.
Microwave method. A solution of 3a-d (0.01 mol) in ethanol (10 mL) and hydrazine
monohydrate (0.02 mol) were taken in a closed vessel. The mixture was irradiated in microwave
at 120 ºC and 10 min (hold time, 7 bar) at 300 Watt maximum power. After the reaction was
completed (monitored as stated above), the mixture was cooled down to room temperature,
taken in a beaker and a white solid appeared. This crude product was filtrated and purification
methods mentioned above were applied.
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2-[2-(2-Methylbenzyl)-5(6)-nitro-1H-benzimidazol-1-yl]acetohydrazide (4a). m.p.: 250-252 °C,
IR (KBr): 3298 (NH,NH2), 3049 (Ar-H), 1656 (C=O), 1610 (C=N), 1513, 1315 (NO2) cm-1. 1H-
NMR (200 MHz, DMSO-d6) δ: 9.65 (s, 1H, NH), 8.44 (s, 1H, Ar-H), 8.25 (d, 1H, J = 8.1 Hz,
Ar-H), 8.13 (d, 1H, J = 8.1, Ar-H), 7.83-7.19 (m, 4H, Ar-H), 4.92 (2H, s, N-CH2), 4.36 (2H,s,
NH2), 4.17 (2H, q, J = 7.2, CH2), 2.27 (3H, t, J = 7.2, CH3). 13C-NMR (50 MHz, DMSO-d6) δ:
165.3 (C=O), 158.1 (C=N), 149.1 (C), 144.2 (C), 142.6 (C), 137.3 (C), 135.4, 133.7 (CH),
129.2 (CH), 127.7 (CH), 126.9 (CH), 122.9 (CH), 120.1 (CH), 118.5 (CH), 50.2 (CH2), 35.3
(CH2), 19.5 (CH3). ESI-MS m/z (rel. int.) 340 [M+1] (100), 305 (26), 267 (52), 235 (34). Anal.
C 60.17%, H 5.05%, N 20.64 %, calcd. for C17H17N5O3, C 60.13%, H 5.05%, N 20.65 %.
2-[2-(3-Methylbenzyl)-5(6)-nitro-1H-benzimidazol-1-yl]acetohydrazide (4b). m.p.: 255-256 °C,
IR (KBr): 3299 (NH, NH2), 3032 (Ar-H), 1654 (C=O), 1619 (C=N), 1510, 1312 (NO2) cm-1. 1H-
NMR (200 MHz, DMSO-d6) δ: 9.75 (s, 1H, NH), 8.52 (s, 1H, Ar-H), 8.31 (d, 1H, J = 8.0 Hz,
Ar-H,), 8.18 (d, 1H, J = 8.0, Ar-H), 7.91-7.23 (m, 4H, Ar-H), 4.89 (2H, s, N-CH2), 4.32 (2H,s,
NH2), 4.14 (2H, s, CH2), 2.27 (3H, s, CH3). 13C-NMR (50 MHz, DMSO-d6) δ: 167.1 (C=O),
159.2 (C=N), 150.3 (C), 146.3 (C), 144.7 (C), 139.2 (C), 137.3, 133.5 (CH), 129.1 (CH), 125.3
(CH), 122.4 (CH), 121.4 (CH), 120.4 (CH), 117.3 (CH), 48.2 (CH2), 33.3 (CH2), 17.9 (CH3).
ESI-MS m/z (rel. int.) 340 [M+1] (100), 305 (29), 267 (57), 235 (63). Anal. C 60.17%, H
5.05%, N 20.64 %, calcd. for C17H17N5O3, C 60.15%, H 5.02%, N 20.67 %.
2-[2-(2-Chlorobenzyl)-5(6)-nitro-1H-benzimidazol-1-yl]acetohydrazide (4c). m.p.: 245-246 °C,
IR (KBr): 3309 (NH, NH2), 3012 (Ar-H), 1657 (C=O), 1617 (C=N), 1511, 1310 (NO2) cm-1. 1H-
NMR (200 MHz, DMSO-d6) δ: 9.89 (s, 1H, NH), 8.58 (s, 1H, Ar-H), 8.38 (d, 1H, J = 8.1 Hz,
Ar-H), 8.18 (d, 1H, J = 8.1, Ar-H), 7.91-7.20 (m, 4H, Ar-H), 4.93 (2H, s, N-CH2), 4.30 (2H,s,
NH2), 4.11 (2H, s, CH2). 13C-NMR (50 MHz, DMSO-d6) δ: 168.1 (C=O), 160.2 (C=N), 151.3
(C), 147.3 (C), 145.7 (C), 140.2 (C), 137.9, 133.1 (CH), 129.6 (CH), 125.4 (CH), 122.8 (CH),
121.1 (CH), 120.4 (CH), 117.3 (CH), 48.2 (CH2), 36.0 (CH2). ESI-MS m/z (rel. int.) 362 [M+3]
(35), 360 [M+1] (100), 325 (50), 295 (9) 293 (29), 177 (32). Anal. C 53.42%, H 3.92%, N
19.47 %%, calcd. for C16H14ClN5O3, C 53.41%, H 3.93%, N 19.45 %.
2-[2-(3-Chlorobenzyl)-5(6)-nitro-1H-benzimidazol-1-yl]acetohydrazide (4d). m.p.: 250-251 °C,
IR (KBr): 3300 (NH, NH2), 3009 (Ar-H), 1655 (C=O), 1610 (C=N), 1511, 1313 (NO2) cm-1. 1H-
NMR (200 MHz, DMSO-d6) δ: 9.81 (s, 1H, NH), 8.60 (s, 1H, Ar-H), 8.28 (d, 1H, J = 8.0 Hz,
Ar-H,), 8.18 (d, 1H, J = 8.0, Ar-H), 7.71-7.10 (m, 4H, Ar-H), 4.96 (2H, s, N-CH2), 4.41 (2H,s,
NH2), 4.23 (2H, s, CH2). 13C-NMR (50 MHz, DMSO-d6) δ: 170.6 (C=O), 161.3 (C=N), 151.9
(C), 148.9 (C), 146.0 (C), 143.2 (C), 138.9, 135.9 (CH), 132.6 (CH), 128.4 (CH), 125.0 (CH),
121.8 (CH), 120.0 (CH), 115.9 (CH), 51.3 (CH2), 37.4 (CH2). ESI-MS m/z (rel. int.) 362 [M+3]
(35), 360 [M+1] (100), 325 (41), 295 (13) 293 (20), 177 (52). Anal. C 53.42%, H 3.92%, N
19.47 %%, calcd. for C16H14ClN5O3, C 53.44%, H 3.90%, N 19.49 %.
ACKNOWLEDGEMENT
This study was funded by the Scientific and Technological Research Council of Turkey
(TUBITAK, project no: 108T356).
REFERENCES
1. Sierra-Zenteno, A.; Galán-Vidal, C.; Tapia-Benavides, R. J. Mex. Chem. Soc. 2002, 46, 125.
2. Küçükbay, H.; Yılmaz, Ü.; Şireci, N.; Önganer, A.N. Turk. J. Chem. 2011, 35, 561.
Bull. Chem. Soc. Ethiop. 2013, 27(2)

Microwave-assisted synthesis of some 5(6)-nitro-1H-benzimidazoles and their hydrazides 271
3. Yalçın, İ.; Şener, E.; Özden, T.; Özden, S.; Akın, A. Eur. J. Med. Chem. 1990, 25, 705.
4. Alamgir, M.; Black, D.S.C.; Kumar, N. Top. Heterocycl. Chem. 2007, 9, 87.
5. Reddy, A.C.S.; Rao, P.S.; Venkataratnam, R.V. Tetrahedron Lett. 1996, 37, 2845.
6. Boufatah, N.; Gellis, A.; Maldonado, J.; Vanelle P. Tetrahedron 2004, 41, 9131.
7. Khurana, J.M.; Vij, S.; Vij, K. Synth. Commun. 2012, 42, 2606.
8. Dawood, K.M.; Abdel-Wahab B.F. Arkivoc 2010, 333.
9. Dawood, K.M.; Elvan, N.M.; Abdel-Wahab B. F. Arkivoc 2011, 111.
10. Varma, R.S. Microwave in Organic Synthesis, Wiley-VCH: Weinheim; 2012; Chap. 6, pp.
181.
11. Kappe, C.O. Angew. Chem. Int. Ed. 2004, 43, 6250.
12. Pinner, A. Die Imidoäther und ihre Derivate, 1 Auflage; Oppenheim: Berlin; 1892.
13. Kahveci, B. Molecules 2005, 10, 376.
14. İkizler, A.A.; Ün, R. Chim. Acta Turc. 1979, 7, 269.
15. Desai, K.G.; Desai, K.R. Bioorg. Med. Chem. 2006, 14, 8271.
16. Gowda, J.; Khadar, A.M.A.; Kumari, B.K.; Kumari, N.S. Indian J. Chem. 2010, 49, 1130.
17. Salman, A.S.S. J. Am. Sci. 2011, 7, 625.
18. Hunger, A.; Kebrle, J.; Rossi, A.; Hoffmann, K. Helv. Chim. Acta 1960, 43, 1032.
Bull. Chem. Soc. Ethiop. 2013, 27(2)