Rapid and cheap synthesis of benzimidazoles via intermittent microwave promotion: A simple and potential industrial application of air as oxidant

Article abstract of DOI:10.1080/00397910903219328

Using inexpensive KI as the catalyst in the presence of ambient air, benzimidazoles were synthesized from aromatic aldehydes and o-phenylenediamine with excellent yields via intermittent microwave irradiation without reflux equipment. The synthesis process was mild and only needed only a short reaction time (7-10min). As a simple example of the utilization of molecular oxygen under mild conditions, this method provides a novel way to synthesize benzimidazoles. The industrial synthesis of benzimidazoles may be realized by a cycle of microwave irradiation. Copyright

Full text of DOI:10.1080/00397910903219328

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Rapid and Cheap Synthesis of
Benzimidazoles via Intermittent
Microwave Promotion: A Simple and
Potential Industrial Application of Air as
Oxidant
Zhengzhou Mao a , Zhaoyang Wang a , Jingning Li a , Xiumei Song a &
Yufen Luo a
a Department of Chemistry, South China Normal University,
Guangzhou, China
Version of record first published: 08 Jun 2010
To cite this article: Zhengzhou Mao, Zhaoyang Wang, Jingning Li, Xiumei Song & Yufen Luo (2010):
Rapid and Cheap Synthesis of Benzimidazoles via Intermittent Microwave Promotion: A Simple and
Potential Industrial Application of Air as Oxidant, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 40:13, 1963-1977
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Synthetic Communications1, 40: 1963–1977, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219328
RAPID AND CHEAP SYNTHESIS OF BENZIMIDAZOLES
VIA INTERMITTENT MICROWAVE PROMOTION:
A SIMPLE AND POTENTIAL INDUSTRIAL APPLICATION
OF AIR AS OXIDANT
Zhengzhou Mao, Zhaoyang Wang, Jingning Li, Xiumei Song,
and Yufen Luo
Department of Chemistry, South China Normal University,
Guangzhou, China
Using inexpensive KI as the catalyst in the presence of ambient air, benzimidazoles were
synthesized from aromatic aldehydes and o-phenylenediamine with excellent yields via
intermittent microwave irradiation without reflux equipment. The synthesis process was
mild and only needed only a short reaction time (7–10 min). As a simple example of the
utilization of molecular oxygen under mild conditions, this method provides a novel way
to synthesize benzimidazoles. The industrial synthesis of benzimidazoles may be realized
by a cycle of microwave irradiation.
Keywords: Ambient air; benzimidazole; intermittent; microwave promotion; molecular oxygen
INTRODUCTION
The use of molecular oxygen has gained considerable attention in recent
years.[1] Usually, transition-metal complexes are used as catalysts in the reports,
where molecular oxygen was the oxidant, especially for oxidation and epoxidation.[2]
Recently, the use of metal-free catalysts is becoming another research hotspot.[3]
However, these methods often suffer from one or more limitations, such as expensive
reagents, long reaction times, high oxygen pressures, special solvents [e.g., supercri-
tical carbon dioxide (scCO2)],[4] or other harsh reaction conditions. Therefore, to
determine how to use molecular oxygen (especially air) under mild conditions and
to promote its industrial application remain important challenges.
Benzimidazole is a very useful intermediate for pharmaceutical and organic syn-
thesis. Its derivatives have various physiological and pharmacological activities and
are used as antivirals, anticancer treatments, antifungals, and anti-inflammatories as
well as in treatment of hypoglycemia and physiological disorders, and they have other
pharmacological effects.[5] As a ligand with transition metals, its complexes can
simulate biological systems.[6] Some benzimidazole derivatives can be used as epoxy
Received June 5, 2008.
Address correspondence to Zhaoyang Wang, Department of Chemistry, South China Normal
University, Guangzhou 510006, China. E-mail: wangwangzhaoyang@tom.com
1963

1964
Z. MAO ET AL.
Scheme 1. The synthesis of benzimidazoles from aldehydes in the presence of oxidant.
resin curing agents, catalysts, and metallic surface treatment agents.[7] Therefore, the
preparation of benzimidazole and its derivatives becomes more and more important.
For the synthesis of 2-substituted benzimidazoles, a general method is the conden-
sation of o-phenylenediamines with carboxylic acids or their derivatives (esters,
nitriles, imidates, or orthoesters), which is usually catalyzed by strong acidic sub-
stances at very high temperature.[8] The use of microwave irradiation has been proven
to be very helpful.[9] To further simplify the situation, the synthesis of benzimidazoles
from aldehydes instead of carboxylic acids or their derivatives in the presence of
different oxidants was proposed (Scheme 1).[10] Recently, more oxidants, such as the
I2=KI=K2CO3=H2O system,[11] (bromodimethyl) sulfonium bromide,[12] and hyperva-
lent iodine,[13] have been reported.
Those oxidants can efficiently produce benzimidazoles, but most of them or their
derivative by-products were toxic. These by-products also made the separation and puri-
fication of the normal products difficult. Undoubtedly, if the molecular oxygen is used as
an oxidant, the mentioned problems could be avoided. However, it was necessary to use
the Fe(III)=Fe(II) redox system as a catalyst.[14] From Singh et al.’s standpoint, many
catalysts, such as active carbon,[15] In(OTf)3,[16] and Yb(OPf)3,[17] have been proposed
under different conditions, for example, higher temperature (120ꢀC) and longer reaction
time (26h) in xylene[15] or reflux in fluorous solvents for 6 h.[17] Only Lin and Yang[18]
gave an example without the use of a catalyst, but the reflux time at 100ꢀC was 4 h. Thus,
applications using inexpensive air as the oxidant to economically and efficiently synthe-
size benzimidazoles in a more environmentally friendly way are attractive.
As an important technique in green synthetic chemistry, microwave-assisted
organic synthesis (MAOS) has received much attention in recent years because it can
achieve greater yields at a shorter reaction time than conventional heating methods.[19,20]
However, it is still necessary to explore how to avoid overheating,[20,21] especially because,
as a result of various defects,[20] domestic microwave ovens are relatively little used in
MAOS.[22] Recently, the method of intermittent microwave irradiation has begun to be
applied in many fields, including the synthesis of inorganic catalysts.[23] Similarly, how
about using intermittent microwaves in synthetic organic chemistry irradiation, especially
when produced by domestic microwave oven? May it prevent the defect effectively?
Herein, we describe a simple, efficient procedure via intermittent heating with
domestic microwave oven for the synthesis of benzimidazoles 3 only using air as the
oxidant and inexpensive KI as the catalyst (Scheme 2).
Scheme 2. The synthesis of benzimidazoles in the presence of air=KI via intermittent MW.

RAPID SYNTHESIS OF BENZIMIDAZOLES VIA AIR
1965
RESULTS AND DISCUSSION
Influences of the Intermittent Microwave Method
To use atmospheric molecular oxygen as oxidant, a grinding synthesis, without
solvent, at room temperature was investigated. The yield was disappointing (Table 1,
entry 1), even after adding strong oxidants (e.g., H2O2) into the system during the
reaction. The yield was gradually improved when the microwave promotion was
introduced. The appropriate reaction conditions are discussed in detail.
For the application of domestic microwave oven in organic synthesis, the main
drawback is the lack of temperature and pressure control.[20,24] Therefore, when a
domestic microwave oven was used in our experiments, we adopted the intermittent
heating method and investigated the influences of intermittent heating method to
avoid higher temperatures (usually no more than 60 ꢀC).
The influence of different microwave powers from 160 to 800 W was assessed
(Table 1, entries 2–7). The yield increased with the increase of power, then decreased.
The greatest yield was 57% at 320 W (Table 1, entry 4). When the power was less,
the energy may be not enough for the reaction to take place, and the result was
unsatisfactory. Greater power also yielded poor results, as the greater reaction
temperature was disadvantageous to both the yield and the operation.
Table 1. Influences of intermittent heating methoda
Entry
Power (W)
Time
Energy transfer medium
Yield (%)b
c
1
2
—
2 h
—
—
11
16
160
240
320
480
640
800
320
320
320
320
320
320
320
320
320
320
30 s ꢁ 10
30 s ꢁ 10
30 s ꢁ 10
30 s ꢁ 10
30 s ꢁ 10
30 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 2
40 s ꢁ 4
40 s ꢁ 6
40 s ꢁ 8
40 s ꢁ 10
40 s ꢁ 14
40 s ꢁ 10
40 s ꢁ 10
50 s ꢁ 10
3
—
—
34
57
4
5
—
—
51
42
6
7
—
—
22
60
8
9
DMF
DMF
DMF
DMF
DMF
DMF
Glycol
Dioxane
DMF
—
10
11
12
13
14
15
16
17
Trace
31
45
70
57
64
61
68
aAll reactions catalyzed by SnCl2.
bIsolated yield via recrystallization or column chromatography.
cGrinding synthesis.

1966
Z. MAO ET AL.
The intermittent heating time was another important factor. For each reaction
time in intermittent microwave heating, the corresponding experiments (Table 1,
entries 4, 8, 13, and 17) showed that 40 s was a suitable time, and the yield was
70% (entry 13). The comparative experiments of different numbers of heating cycles
(Table 1, entries 8–14) showed that the optimal number of times was 10 and the yield
was 70% if using N,N-dimethylformamide (DMF) as the energy transfer medium
(entry 13). Therefore, the optimal reaction time was 40 s ꢁ 10.
Without DMF, the reaction under the same optimal reaction time gave a yield
of only 60% (Table 1, entry 8). This indicated that the energy transfer medium was
important for the solvent-free reaction promoted by microwaves. Among different
organic compounds with high boiling points (Table 1, entries 13, 15, and 16), the best
energy transfer medium was DMF, because DMF has a high boiling point (160 ꢀC)
and higher dielectric constant.[25] At the same time, DMF is soluble in water, which
simplified the experimental procedure. Thus, DMF was selected as the energy
transfer medium.
Influences of Other Reaction Conditions
At the same time, the influences of other reaction conditions were investigated.
The results are shown in Table 2. Of all catalysts (Table 2, entries 1–8), the best was
Table 2. Influences of other reaction conditionsa
Entry
Catalysts
Desiccant (mol%)
Yield (%)b
1
2
SnCl2
SnCl4
—
70
51
47
59
38
43
40
84
86
82
88
83
87
85
90
89
86
81
—
—
3
KHSO4
Active carbon
4
—
—
5
CoCl2
HCl
ZnCl2
KI
6
—
—
7
8
—
9
KI
KI
MgSO4 (5)
Al2O3 (5)
Na2SO4 (5)
Allochroic silica gel (5)
CaCl2 (5)
Na2SO4 (1)
Na2SO4 (10)
Na2SO4 (15)
Na2SO4 (20)
Na2SO4 (30)
10
11
12
13
14
15
16
17
18
KI
KI
KI
KI
KI
KI
KI
KI
aAll reactions intermittently promoted by a 320-W domestic microwave oven using DMF as the energy
transfer medium, and the reaction time was 40 s ꢁ 10.
bIsolated yield via recrystallization or column chromatography.

RAPID SYNTHESIS OF BENZIMIDAZOLES VIA AIR
1967
KI (yield 84%, entry 8). Compared with stannous chloride (yield 70%, entry 1), the
reaction catalyzed by KI gave greater yield, and the separation and purification of
products was simpler. Thus, KI was extensively used as the catalyst in the following
experiments. The catalytic mechanism of KI may be in touch with the formation of
the redox system of Iꢂ=I2.[11]
To our surprise, adding some desiccants into the reaction system can to some
extent improve the yield (Table 2, entries 9–13). Anhydrous sodium sulfate gave the
best result (yield 88%, entry 11). Notably, the suitable dosage of the desiccant
Na2SO4 was 10 mol%; more or less did not produce satisfactory results (Table 2,
entries 14–18). Thus, under the optimal conditions of all the factors, the greatest
yield was 90% (entry 15).
Reaction of Different Substrates
To test the generality and versatility of this procedure in the synthesis of sub-
stituted benzimidazoles, a number of 4-substituted o-phenylenediamines 1 and aro-
matic aldehydes 2 were examined according to the optimized conditions. The results
are shown in Table 3. Usually, both electron-rich and electron-deficient benzalde-
hydes gave 2-aryl-benzimidazoles 3 in good to excellent yields (mostly more than
Table 3. Isolated yield for the synthesis of substituted benzimidazolesa
Entry
R1
Ar
Product
Time
Yield (%)
1
2
H
H
Ph-
p-HOPh-
p-ClPh-
3a
3b
3c
3d
3e
3f
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 12
40 s ꢁ 15
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 15
40 s ꢁ 12
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 10
40 s ꢁ 15
40 s ꢁ 15
40 s ꢁ 15
40 s ꢁ 15
40 s ꢁ 15
90
67
74
83
79
72
86
81
77
82
67
87
86
84
88
80
82
80
3
H
4
H
p-NO2Ph-
p-N(CH3)2Ph-
p-CH3OPh-
p-CH3Ph-
5
H
6
H
7
H
3g
3h
3i
8
H
m-CH3Ph-
m-NO2Ph-
2,4-Dichloro-Ph-
3-CH3O-4-OH-Ph-
Ph-
9
H
10
11
12
13
14
15
16
17
18
H
3j
H
3k
3l
CH3
CH3
CH3
CH3
NO2
NO2
NO2
p-ClPh-
3m
3n
3o
3p
3q
3r
p-N(CH3)2Ph-
2,4-Dichloro-Ph
Ph-
p-ClPh-
p-N(CH3)2Ph-
aAll reactions carried out in the presence of DMF as energy transfer medium and catalyzed by KI
(15 mol%). All products were isolated via recrystallization or column chromatography and confirmed
by spectral data (IR, 1H NMR, and 13C NMR).

1968
Z. MAO ET AL.
Scheme 3. The synthesis of benzimidazole from terephthalaldehyde in the presence of air=KI.
80%). Perhaps because of the oxidation of the hydroxyl group, the aromatic
aldehydes 2 with hydroxyl group often gave poor yields, but the yield was still
satisfactory (Table 3, entries 2 and 11). It is noteworthy that, in all cases, the reaction
was completed in about 7–10 min.
When an aromatic aldehyde with two aldehyde groups, such as terephthalalde-
hyde 4 (5 mmol), was reacted with o-phenylenediamine (12 mmol) under a similar
procedure, a bisbenzimidazole 5 was synthesized with excellent yield in a short time
(Scheme 3). The result also indicated that this procedure had good generality and
versatility for the synthesis of substituted benzimidazoles.
Industrialization Potential
Because of their various disadvantages,[20,24] domestic microwave ovens have
not been used much in MAOS.[22] In these experiments for the synthesis of benzimi-
dazole, the use of a domestic microwave oven was exploited for intermittent heating
to prevent overheating. At the same time, air was introduced into the reaction
systems as a reagent in the reaction during the cooling process. Thus, the intermittent
heating in a domestic microwave oven had a dual purpose. Our design yielded good
results (Table 3).
Importantly, according to Cablewski’s idea of large-scale synthesis using
microwave heating,[20,26] the method of intermittent microwave heating also may
be industrialized using a cyclic design for continuous equipment (Scheme 4).
In Scheme 4, the spots labeled with numbers (such as 1, 2, 3, 4, 5) represent the
reaction equipment, and the spots labeled with letters (such as A, B, C, D, E)
represent the cooling in air when the microwave heating is stopped and the door
is open. In industry, we can design a disc with microwave heating equipment
arranged evenly around the disc. The reactor is fixed on it also but can be moved
in accordance with the preplanned rate as needed. For example, if we want to syn-
thesize benzimidazole (3a) via 10 periods of intermittent heating, we could start the
reaction at 1, and then cool it by air at A. When the first reactor is moved to 2, the
second is at 1, and so on. Thus, the reaction is carried out simultaneously in different
reactors. The process is repeated until the reaction time is sufficient, and then the
reactor is taken out at E (if at this point the reaction is finished).
It is very valuable for green chemistry and industrial production to obtain the
same excellent result via the simplest method or technology. Obviously, a domestic
microwave oven is much simpler than many microwave apparatuses with reflux
equipment or other complex structures, such as a pump.[20,26] Especially from an

RAPID SYNTHESIS OF BENZIMIDAZOLES VIA AIR
1969
Scheme 4. The industrial design for the synthesis of benzimidazoles using air as oxidant via
intermittent MW.
industrialization standpoint, simple equipment is not only inexpensive but also safe
and easily designed to avoid microwave leakage.
Therefore, the utilization of the intermittent microwave heating is advan-
tageous to shorten the reaction time and take full advantage of the molecular oxygen
in air. It also has potential industrial value for the synthesis of benzimidazoles on a
large scale.
CONCLUSION
In summary, a simple, practical, and efficient method for the synthesis of
2-substituted benzimidazoles from o-phenylenediamines and aromatic aldehydes
using molecular oxygen as an oxidant was developed in this study. The mild reaction
conditions, short reaction time, simple procedure, and potential for industrialization
are the main advantages of this method, which make it a valid contribution to the
existing methodologies.
EXPERIMENTAL
An 800-W household microwave oven[22] (2.45 GHz) was used for microwave
heating, and the microwave irradiation was intermittent at the appropriate power.
NMR spectra were recorded on a Varian NMR system 400 spectrometer using
dimethylsulfoxide (DMSO-d6) as an internal reference and solvent except for 3n,
which used CDCl3 as an internal reference and solvent. Infrared (IR) spectra
were recorded on a Fourier transform (FT)–IR spectrophotometer. Melting
points were obtained using an X-5 micromelting-point measuring instrument

1970
Z. MAO ET AL.
(uncorrected). Mass spectra (MS) were performed on a ThermoFinnigan trace DSQ
apparatus instrument. All o-phenylenediamines, aromatic aldehydes, and catalysts
were commercially purchased and used without further purification.
Typical Procedure
A mixture of o-phenylenediamine (5 mmol), aromatic aldehyde (6 mmol),
dimethylformamide (DMF; typically 0.5 mL), and KI (typically 124.5 mg, 15mol%)
was added in an Erlenmeyer flask (25 mL). The flask was placed in a domestic micro-
wave oven at a frequency of 2450 Hz (800 W) and was intermittently irradiated in a
microwave cavity with an output at 40% (320 W) for 40 s per irradiation. The reac-
tion time of each irradiation was controlled to avoid a higher temperature. Usually,
the temperature was no more than 60 ꢀC, and the flask could be taken out of the
oven by hand. Once the microwave heating was stopped, the door of domestic micro-
wave oven was opened. All microwave experiments were carried out at atmospheric
pressure and monitored by thin-layer chromatography (TLC). After the reaction was
finished, the reaction mixture was diluted with ethyl acetate (40 mL) and then washed
with saturated sodium bicarbonate solution (20 mL) and water (20 mL) in sequence.
The combined organic layer was dried over Na2SO4 and concentrated under reduced
pressure to furnish the crude product, which was further purified by recrystallization
with ethanol or silica-gel chromatography using EtOAc=petroleum ether (1:4). All
1
products were characterized with FT-IR, H NMR, and 13C NMR. Some products
selected at random were further confirmed by MS.
Data
2-Phenylbenzimidazole (3a). White powder, mp 290–292 ꢀC (289–291 ꢀC).[17]
1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.17–7.24 (m, 2H, Ar-H), 7.49–7.57 (m, 4H,
Ar-H), 7.66 (d, 1H, Ar–H), 8.17 (d, 2H, Ar-H), 12.90 (s, 1H, N-H); 13C NMR
(DMSO-d6, 100 MHz), d, ppm: 111.98, 119.55, 123.19, 127.11, 129.62, 130.49,
144.49, 151.88; IR (KBr), v, cmꢂ1: 3406, 3047, 1589, 1540, 1443, 1409, 1483, 1275,
1118, 736, 704; MS, m=z: 193.97 (Mþ).
2-(4-Hydroxyphenyl)benzimidazole (3b). White powder, mp 229–230 ꢀC
(229–231 ꢀC).[27] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 5.43 (s, 1H, OH), 6.67
(s, 1H, Ar-H), 6.91 (s, 2H, Ar-H), 7.21 (d, 1H, Ar-H), 7.43 (d, 1H, Ar-H),
7.58–7.65 (m, 3H, Ar-H); 13C NMR (DMSO-d6, 100 MHz), d, ppm: 111.59,
116.19, 122.76, 128.14, 131.24, 136.51, 143.37, 157.32; IR (KBr), v, cmꢂ1: 3376,
3290, 3027, 2807, 1697, 1611, 1591, 1515, 1443, 1394, 1268, 1246, 839, 745. MS,
m=z: 210 (Mþ).
2-(4-Chlorophenyl)benzimidazole (3c). White powder, mp 291–293 ꢀC
(292–294 ꢀC).[28] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.20–7.23 (m, 2H,
Ar-H), 7.59–7.65 (m, 4H, Ar-H), 8.19 (d, 2H, Ar-H); 13C NMR (DMSO-d6,
100 MHz), d, ppm: 118.53, 122.94, 128.70, 128.79, 129.58, 129.68, 135.16, 150.85;
IR (KBr), v, cmꢂ1: 3051, 1586, 1490, 1448, 1429, 1272, 831, 745, 728.

RAPID SYNTHESIS OF BENZIMIDAZOLES VIA AIR
1971
2-(4-Nitrophenyl)benzimidazole (3d). Yellow powder, mp 313–314 ꢀC
(312–314 ꢀC).[17] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.28 (d, 2H, Ar-H),
7.60–7.74 (m, 2H, Ar-H), 8.42 (s, 4H, Ar-H), 13.29 (s, 1H, N-H); 13C NMR
(DMSO-d6, 100 MHz), d, ppm: 112.41, 120.07, 123.09, 124.90, 128.03, 136.71,
148.45, 149.66; IR (KBr), v, cmꢂ1: 3042, 1604, 1515, 1434, 1353, 854, 745, 710.
2-(4-N,N-Dimethylaminophenyl)benzimidazole (3e).[29] White powder,
1
mp 288–290 ꢀC. H NMR (DMSO-d6, 400 MHz), d, ppm: 2.99 (s, 6H, CH3), 6.82
(d, 2H, Ar-H), 7.10–7.13 (m, 2H, Ar-H), 7.48 (d, 2H, Ar-H), 7.97 (d, 2H, Ar-H);
13C NMR (DMSO-d6, 100 MHz), d, ppm: 31.35, 104.98, 112.55, 118.12, 118.69,
122.15, 128.23, 151.93, 152.97; IR (KBr), v, cmꢂ1: 3395, 3194, 2924, 1630, 1578,
1469, 1433, 1275, 1090, 837, 731.
2-(4-Methoxyphenyl)benzimidazole (3f). White powder, mp 221–222 ꢀC
(224–226 ꢀC).[12] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 3.84 (s, 3H, CH3),
7.12–7.18 (m, 4H, Ar-H), 7.56 (s, 2H, Ar-H), 8.13 (s, 2H, Ar-H); 13C NMR
(DMSO-d6, 100 MHz), d, ppm: 55.99, 115.02, 115.43, 122.41, 123.47, 128.71,
140.15, 152.11, 161.29; IR (KBr), v, cmꢂ1: 3048, 2934, 1611, 1500, 1457, 1405,
1371, 1251, 843, 745.
2-(4-Methylphenyl)benzimidazole (3g). White powder, mp 273–275 ꢀC
(270 ꢀC).[28] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 2.38 (s, 2H, CH3), 7.14–7.21
(m, 2H, Ar-H), 7.37 (d, 2H, Ar-H), 7.58 (d, 2H, Ar-H), 8.08 (d, 2H, Ar-H), 12.90
(s, 1H, N-H); 13C NMR (DMSO-d6, 100 MHz), d, ppm: 21.65, 111.87, 119.38,
122.43, 127.08, 128.17, 130.16, 140.22, 152.08; IR (KBr), v, cmꢂ1: 3052, 2914,
1621, 1449, 1430, 1398, 1376, 1273, 821, 746.
2-(3-Methylphenyl)benzimidazole (3h).[30] White powder, mp 212–214 ꢀC.
1H NMR (DMSO-d6, 400 MHz), d, ppm: 2.38 (s, 3H, CH3), 7.19 (s, 2H, Ar-H), 7.32
(d, 1H, Ar-H), 7.41–7.45 (m, 1H, Ar-H), 7.52 (d, 1H, Ar-H), 7.64 (d, 1H, Ar-H),
7.91–8.02 (m, 2H, Ar-H), 13C NMR (DMSO-d6, 100 MHz), d, ppm: 21.67, 111.95,
119.50, 122.70, 124.27, 127.69, 129.46, 131.09, 138.80, 152.04; IR (KBr), v, cmꢂ1
:
3425, 3064, 2969, 1624, 1589, 1447, 1403, 1277, 838, 742.
2-(3-Nitrophenyl)benzimidazole (3i). Yellow powder, mp 188–190 ꢀC (189–
191 ꢀC).[31] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.13–7.19 (m, 2H, Ar-H), 7.49
(d, 1H, Ar-H), 7.63 (d, 1H, Ar-H), 7.50–7.79 (m, 1H, Ar-H), 8.23 (d, 1H, Ar-H), 8.51
(d, 1H, Ar-H), 8.92 (s, 1H, Ar-H); 13C NMR (DMSO-d6, 100 MHz), d, ppm: 116.05,
121.38, 123.25, 124.64, 131.07, 132.32, 132.98, 139.70, 148.85, 149.63; IR (KBr), v,
cmꢂ1: 3108, 1620, 1520, 1476, 1435, 1348, 1227, 812, 740.
2-(2,4-Dichlorophenyl)benzimidazole (3j).[31] White powder, mp 218–219ꢀC.
1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.21–7.23 (m, 2H, Ar-H), 7.56 (d, 1H, Ar-H),
7.60–7.64 (m, 2H, Ar-H), 7.83 (d, 1H, Ar-H), 7.93–7.96 (m, 1H, Ar-H); 13C NMR
(DMSO-d6, 100 MHz), d, ppm: 116.15, 122.86, 128.30, 130.51, 133.25,
133.90, 135.51, 139.87, 149.10; IR (KBr), v, cmꢂ1: 3059, 1619, 1593, 1440, 1421,
1269, 836, 750.
2-(4-Hydroxy-3-methoxyphenyl)benzimidazole (3k). White powder, mp
219–221 ꢀC (224– 225 ꢀC).[27] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 3.89 (s, 3H,

1972
Z. MAO ET AL.
CH3), 6.90 (d, 1H, Ar-H), 7.13–7.17 (m, 2H, Ar-H), 7.53 (s, 2H, Ar-H), 7.60 (d, 1H,
Ar-H), 7.74 (s, 1H, Ar-H), 9.50 (s, 1H, OH), 12.63 (s, 1H, N-H); 13C NMR (DMSO-
d6, 100 MHz), d, ppm: 56.36, 111.04, 116.30, 116.42, 120.33, 120.41, 122.09, 122.51,
148.52, 149.13, 152.47; IR (KBr), v, cmꢂ1: 3459, 3325, 2937, 1590, 1503, 1440, 1403,
1271, 1219, 1030, 744. MS, m=z: 240 (Mþ).
5-Methyl-2-phenylbenzimidazole (3l). White powder, mp 242–243 ꢀC
(242–243 ꢀC).[12] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 2.41 (s, 3H, CH3),
6.97–7.03 (m, 1H, Ar-H), 7.38 (d, 2H, Ar-H), 7.43–7.46 (m, 2H, Ar-H), 7.49–7.53
(m, 2H, Ar-H), 8.12 (d, 1H, Ar-H), 12.69 (s, 1H, N-H); 13C NMR (DMSO-d6,
100 MHz), d, ppm: 21.96, 111.79, 119.38, 124.17, 124.86, 128.67, 129.89, 132.86,
142.65, 150.65; IR (KBr), v, cmꢂ1: 3406, 2921, 1630, 1578, 1463, 1403, 1309, 1277,
1113, 837, 731.
2-(4-Chlorophenyl)-5-methylbenzimidazole (3m). White powder, mp
227–228 ꢀC (224–225 ꢀC).[12] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 2.43 (s, 3H,
CH3), 7.03 (s, 1H, Ar-H), 7.37 (s, 1H, Ar-H), 7.49 (s, 1H, Ar-H), 7.62 (d, 2H,
Ar-H), 8.16 (d, 2H, Ar-H), 12.84 (s, 1H, N-H); 13C NMR (DMSO-d6, 100 MHz),
d, ppm: 21.96, 111.79, 119.38, 124.17, 124.86, 128.67, 129.89, 132.86, 142.65,
150.65; IR (KBr), v, cmꢂ1: 3390, 3194, 2924, 1630, 1578, 1469, 1443, 1274, 1090,
837, 731.
5-Methyl-2-(4-N,N-dimethylaminophenyl)benzimidazole (3n).[32] White
1
powder, mp 249–251 ꢀC. H NMR (CDCl3, 400 MHz), d, ppm: 2.29 (s, 3H, CH3-
Ar), 3.06 (s, 6H, CH3-N), 4.23 (b, 1H, N-H), 6.55–6.60 (m, 1H, Ar-H), 6.74 (d,
2H, Ar-H), 6.85–6.96 (m, 1H, Ar-H), 7.79–7.82 (m, 2H, Ar-H), 8.40 (s, 1H,
Ar-H); 13C NMR (CDCl3, 100 MHz), d, ppm: 21.40, 40.38, 111.79, 116.11, 170.02,
119.41, 127.19, 130.43, 136.11, 136.58, 142.01, 152.53, 156.91; IR (KBr), v, cmꢂ1
:
3471, 2920, 1609, 1577, 1523, 1450, 1360, 1262, 1161, 814, 800.
2-(2,4-Dichlorophenyl)-5-methylbenzimidazole (3o).[33] White powder,
1
mp 104–106 ꢀC. H NMR (DMSO-d6, 400 MHz), d, ppm: 2.42 (s, 3H, CH3), 7.05
(d, 1H, Ar-H), 7.40 (s, 1H, Ar-H), 7.50 (d, 1H, Ar-H), 7.59–7.62 (m, 1H, Ar-H),
7.79 (d, 1H, Ar-H), 7.93 (d, 1H, Ar-H), 12.63 (s, 1H, N-H); 13C NMR (DMSO-d6,
100 MHz), d, ppm: 21.78, 112.30, 119.26, 124.30, 124.35, 124.37, 128.10, 129.38,
130.30, 132.22, 132.92, 133.60, 135.26, 148.15; IR (KBr), v, cmꢂ1: 3460, 2949,
1631, 1573, 1498, 1455, 1281, 1132, 1031, 801.
5-Nitro-2-phenylbenzimidazole (3p). Yellow powder, mp 203–205 ꢀC
(207–208 ꢀC).[10a] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.57 (s, 2H, Ar-H),
7.59 (s, 1H, Ar-H), 7.74 (d, 1H, Ar-H), 8.09–8.12 (m, 1H, Ar-H), 8.18–8.20 (m,
2H, Ar-H), 8.45 (s, 1H, Ar-H), 13.60 (s, 1H, N-H); 13C NMR (DMSO-d6,
100 MHz), d, ppm: 104.99, 110.77, 118.42, 127.42, 128.80, 129.47, 129.60, 131.42,
137.72, 143.16, 155.20; IR (KBr), v, cmꢂ1: 3411, 1628, 1560, 1485, 1412, 1341,
1270, 1065, 823, 780.
2-(4-Chlorophenyl)-5-nitrobenzimidazole (3q). Yellow powder, mp
306–307 ꢀC (305–308 ꢀC).[10a] 1H NMR (DMSO-d6, 400 MHz), d, ppm: 7.65–7.68
(m, 2H, Ar-H), 7.76 (d, 1H, Ar-H), 8.10 (d, 1H, Ar-H), 8.20 (d, 2H, Ar-H), 8.45
(s, 1H, Ar-H), 13.66 (s, 1H, N-H); 13C NMR (DMSO-d6, 100 MHz), d, ppm:

RAPID SYNTHESIS OF BENZIMIDAZOLES VIA AIR
1973
112.59, 115.58, 118.86, 128.49, 129.26, 129.82, 131.40, 136.30, 143.22, 150.47, 155.07;
IR (KBr), v, cmꢂ1: 3290, 1597, 1537, 1498, 1445, 1333, 1291, 1060, 837, 735.
5-Nitro-2-(4-N,N-dimethylaminophenyl)benzimidazole (3r).[34] Yellow
1
powder, mp 228– 230 ꢀC. H NMR (DMSO-d6, 400 MHz), d, ppm: 3.03 (s, 6H,
CH3), 6.85 (d, 2H, Ar-H), 7.65 (d, 1H, Ar-H), 8.03–8.09 (m, 3H, Ar-H), 8.35 (s,
1H, Ar-H), 13.22 (s, 1H, N-H); 13C NMR (DMSO-d6, 100 MHz), d, ppm: 40.30,
112.19, 112.31, 116.15, 117.92, 128.67, 128.78, 135.16, 142.51, 142.53, 142.55,
152.34; IR (KBr), v, cmꢂ1: 3536, 3171, 1611, 1567, 1500, 1411, 1370, 1313, 1201,
1062, 815, 737.
Bisbenzimidazole (5). Yellow powder, mp > 310 ꢀC (>300 ꢀC).[35] 1H NMR
(DMSO-d6, 400 MHz), d, ppm: 7.16–7.30 (m, 4H, Ar-H), 7.55– 7.70 (m, 4H,
Ar-H), 8.34 (s, 4H, Ar-H), 13.00 (s, 2H, N-H); 13C NMR (DMSO-d6, 100 MHz),
d, ppm: 119.54, 127.67, 131.82, 135.80, 144.52, 151.31; IR (KBr), v, cmꢂ1: 3401,
3069, 1583, 1434, 1404, 1391, 1279, 1017, 741.
ACKNOWLEDGMENTS
The authors are grateful to the National Natural Science Foundation of China
(No. 20772035) and the Natural Science Foundation of Guangdong Province (No.
5300082) for the financial support of this work and to Dr. David E. Finlow (Shawnee
State University) for helpful language correction.
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