An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water

Article abstract of DOI:10.1007/s11696-017-0367-5

An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/ heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO₃ in water had been developed. The amount of NaHSO₃ had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO₃ was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO₃ was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.

Full text of DOI:10.1007/s11696-017-0367-5

Chemical Papers
https://doi.org/10.1007/s11696-017-0367-5
ORIGINAL PAPER
An efcient NaHSO ‑promoted protocol ꢀor chemoselective synthesis
3
oꢀ 2‑substituted benzimidazoles in water
Yu‑qin Jiang1 · Shu‑hong Jia · Xi‑yong Li · Ya‑min Sun · Wei Li · Wei‑wei Zhang · Gui‑qing Xu
1
2
2
1
1
1
Received: 18 April 2017 / Accepted: 6 December 2017
©
Institute of Chemistry, Slovak Academy of Sciences 2017
Abstract
An efcient protocol ꢀor chemoselective synthesis oꢀ 2-substituted benzimidazoles ꢀrom a variety oꢀ aliphatic/aromatic/
heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO in water had been developed. The amount
3
oꢀ NaHSO had a great eꢁect on the reaction selectivity oꢀ 2-substituted benzimidazole and 1,2-disubstituted benzimidazole
3
when the reaction was carried out in water. When the amount oꢀ the NaHSO was more than 11 equivalents, the 2-substi-
3
tuted benzimidazole could be highly selectively ꢀormed as the sole product. NaHSO was ꢂrstly reacted with aldehyde to
3
ꢀ
orm the aldehyde sodium bisulꢂte, which reacted with o-phenylenediamine to ꢀorm the 2-substituted benzimidazole and
inhibited the ꢀormation oꢀ 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in
traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage
oꢀ simple work up by ꢂltrating the single 2-substituted benzimidazole precipitates ꢀrom reaction mixture at the end oꢀ the
reaction without ꢀurther puriꢂcation. In addition, the method was applicable to both electron-rich and electron-poor starting
materials, which was successꢀully used ꢀor synthesizing nine novel 2-substituted benzimidazole derivatives containing a
1
,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied
to a large scale synthesis oꢀ 2-substituted benzimidazole derivatives.
Keywords NaHSO · Chemoselective synthesis · 2-Substituted benzimidazoles · In water · 1,2,3-Triazole
3
Introduction
so on (Porcari et al. 1998; Migawa et al. 1998; Hutchin-
son et al. 2003; Mederski et al. 2004; Huang et al. 2006;
Mavrova et al. 2006; Goossen and Knauber 2008; Shah
et al. 2008; Zhao et al. 2010). In addition, benzimidazoles
are also important building blocks in organic synthesis
(Roth et al. 1997; Horton et al. 2003; Travins et al. 2010)
and ligands to transition metals ꢀor modeling biological
systems (Bouwman et al. 1990; Pujar and Bharamgoudar
1988). The ꢀormation oꢀ these privileged class oꢀ com-
pounds had generated interests to develop newer synthetic
methods. Among them, most oꢀ protocols have ꢀocused
on the synthesis oꢀ the 2-substituted benzimidazoles. The
traditional methods ꢀor the synthesis oꢀ 2-substituted ben-
zimidazoles involve the condensation oꢀ o-phenylenedi-
amines and carboxylic acids (Hendrickson and Hussoin
Benzimidazoles, as a class oꢀ heterocyclic aromatic
organic compounds, have received considerable attentions
in recent years due to their widely biological activities,
such as antihistamines, antiviral, antihypertension and
Electronic supplementary material The online version oꢀ this
article (https://doi.org/10.1007/s11696-017-0367-5) contains
supplementary material, which is available to authorized users.
*
Yu-qin Jiang
jiangyuqin@htu.cn
1
Henan Engineering Laboratory oꢀ Chemical Pharmaceuticals
and Biomedical Materials, Collaborative Innovation
Center oꢀ Henan Province ꢀor Green Manuꢀacturing oꢀ Fine
Chemicals, Key Laboratory oꢀ Green Chemical Media
and Reactions, Ministry oꢀ Education, School oꢀ Chemistry
and Chemical Engineering, Henan Normal University,
Xinxiang, People’s Republic oꢀ China
1
989; Dudd et al. 2003; Maraš and Kocevar 2011; Lin
et al. 2006; Boggu et al. 2016) or their derivatives (Heravi
et al. 2006; Hikawa et al. 2014) under harsh reaction con-
ditions. The most popular method is the oxidative cyclo-
dehydrogenation oꢀ aniline Schiꢁ bases, which is gener-
ated in situ ꢀrom the condensation oꢀ o-phenylenediamine
2
Weihai Ocean Vocational College, Weihai,
People’s Republic oꢀ China
Vol.:(0
1
123456789)
3

Chemical Papers
derivatives (Austen and Kane 2001; Navarrete-Vázquez
et al. 2007) with substituted aldehydes in the presence oꢀ
a suitable oxidizing agent (Eynde et al. 1995; Gogoi and
Konwar 2006; Bai et al. 2014).
advantages oꢀ operational simplicity, excellent yields, high
chemoselectivity as well as clean and green reaction proꢂle.
To chemoselective synthesis oꢀ 2-substituted benzimida-
zoles, some organic solvents had been used (Du and Wang
Experimental
2
007; Chen et al. 2013; Park et al. 2014). In view oꢀ envi-
All reagents were purchased ꢀrom commercial sources and
used without ꢀurther puriꢂcation, unless otherwise indicated.
ronmental and social concerns, water as an inexpensive and
environmentally benign solvent as well as its speciꢂc proper-
ties, has been widely used ꢀor the synthesis oꢀ 2-substituted
benzimidazoles by condensation oꢀ o-phenylenediamines
with substituted aldehydes (Herrera Cano et al. 2016).
Except two cases (Panda and Jain 2011; Bala et al. 2015),
most oꢀ the reported protocols carried out in water need the
addition oꢀ catalysts or oxidants, including ZrOCl ·nH O on
1
The known products were characterized using H NMR and
1
3
C NMR (BrukerAvance 400 MHz or Bruker AVANCE III
HD 600) which used CD OD or DMSO-d . Data are repre-
3
6
sented as ꢀollows: chemical shiꢀt, integration, multiplicity
(s = singlet, d = doublet, dd = double oꢀ doublets, t = tri-
plet, q = quartet, m = multiplet, brs = broad singlet) and
coupling constants (J) in Hertz (Hz).Melting points were
determined on a YUHUA X-5 melting point apparatus and
were reported uncorrected. IR spectra were recorded on a
NEXUS FTIR-Raman Spectrometer. HRMS was perꢀormed
on a MicrOTOF-QII mass spectrometer with an ESI source
(Waters, Manchester).
2
2
montmorillonite K10 (Rostamizadeh et al. 2009), surꢀactants
SDS, DBSA) (Bahrami et al. 2010; Kumar et al. 2013a, b),
laccase (Leutbecher et al. 2011), nano ceria (Shelkar et al.
(
2
+
2
013), glucose (Rostamizadeh et al. 2011), and Cu or a
2
+
Zn ions (Ji et al. 2014). In addition, recyclable catalysts
or oxidants have also been prepared and applied ꢀor the syn-
thesis oꢀ 2-benzimidazoles in water (Ji et al. 2014; Sodhi
and Paul 2011; Dandia et al. 2012; Nezhad et al. 2014). Due
to complex preparation oꢀ the reported recyclable catalyst
systems in aqueous media, ꢂnding a more simple and green
protocol in water is still a challenge ꢀor synthesis oꢀ 2-sub-
stituted benzimidazoles by condensation oꢀ o-phenylenedi-
amines and substituted aldehydes.
General procedure for the synthesis of 2‑substituted
benzimidazole
In a round-bottomed ꢃask (10 mL) equipped with a mag-
netic stirrer, a mixture oꢀ aldehyde (1.0 mmol) and NaHSO
3
(11.0 eq, 1.14 g) in H O (4.0 mL) was prepared. When the
2
mixture reached reꢃuxing temperature, o-phenylenediamine
derivatives (1.0 mmol) were added. The resulting mixture
was stirred ꢀor appropriate time and monitored by HPLC
(Hypersil GOLD 250 × 4.6 mm, 5 µm). Aꢀter completion oꢀ
the reaction, the reaction mixture was vacuum ꢂltered aꢀter
cooling to room temperature by a glass ꢀunnel. The residues
were washed by water (4 mL × 2), dried in air dry oven and
characterized by physical and spectral properties.
At present, the synthesis oꢀ 2-substituted benzimida-
zoles is a challenging task, ꢀor the direct cyclocondensa-
tion between o-phenylenediamine and aldehyde oꢀten leads
to competitive ꢀormation oꢀ the 1,2-disubstituted and the
2
-substituted benzimidazoles (Mirjalili et al. 2014). As we
all known, NaHSO is a special inorganic compound, which
3
could ꢀorm a sodium hydrogen sulꢂte-aldehyde adduct with
aldehyde. NaHSO itselꢀ has been used as the catalyst ꢀor
3
synthesis oꢀ 2-substituted benzimidazoles (López et al.
2
009; Han et al. 2008; Yamashita et al. 2009). Meanwhile,
Results and discussion
the ꢀormed aldehyde bisulꢂte adducts have also been used
as the starting materials instead oꢀ aldehydes to react with
o-phenylenediamines ꢀor synthesizing the 2-substituted ben-
zimidazoles (Ridley et al. 1965; Servi 2002; López et al.
Eꢀect of the loading of NaHSO3
The reaction between benzaldehyde (1) and o-phenylene-
diamine (2) was chosen as the model reaction in the pres-
2
009; Betti et al. 2014). However, these methods had limita-
tions such as the difculty in isolation and puriꢂcation oꢀ the
products or the use oꢀ toxic organic solvent or mixed solvent,
long reaction time with moderate yields. To the best oꢀ our
ence oꢀ NaHSO in water ꢀor optimizing reaction condi-
3
tions (Fig. 1). The progress oꢀ the reaction was monitored
by HPLC.
knowledge, there is no report using NaHSO as a homogene-
Firstly, the model reaction was carried out in the absence
3
ous reagent in water ꢀor chemoselective and high-yielding
preparation oꢀ 2-substituted benzimidazoles ꢀrom various
aldehydes and o-phenylenediamine. The main work reported
oꢀ NaHSO and it took 4 h to complete the reaction. As
3
shown in Fig. 2, the obtained products included 2-phenyl-
1H-benzoimidazole (3) and 1-benzyl-2-phenyl-1H-benzo-
imidazole (4) in the ratio oꢀ 32:68, which indicated that the
chemoselectivity oꢀ the model reaction was poor in water
in this paper is to establish a simple protocol using NaHSO
3
as a homogeneous reagent in water at 100 °C ꢀor chemose-
lective synthesis oꢀ 2-substituted benzimidazoles with the
in the absence oꢀ NaHSO . It was worthy to mention that
3
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Chemical Papers
Fig. 1 Model reaction ꢀor opti-
mizing reaction conditions
Fig. 2 The eꢁect oꢀ the loading oꢀ NaHSO on the chemoselectiv-
3
ity in the model reaction. All reactions were perꢀormed with benza-
ldehyde (1, 1.0 mmol, 106.1 mg), o-phenylenediamine (2, 1.0 mmol,
Fig. 3 The eꢁect oꢀ the temperature on the yield oꢀ model reac-
tion. All reactions were perꢀormed with benzaldehyde (1, 1.0 mmol,
1
08.1 mg), NaHSO and water (4.0 mL) at 80 °C
3
1
06.1 mg), o-phenylenediamine (2, 1.0 mmol, 108.1 mg), NaHSO
3
when more 4 was generated in product, the resulting yellow
(11.0 mmol, 1.14 g) and water (4.0 mL) in 30 min
viscous reaction mixture adhered to the ꢃask. For investi-
gating the eꢁect oꢀ NaHSO on the chemoselectivity oꢀ the
3
model reaction, the ꢀollowing experiments were carried out
in water in the presence oꢀ diꢁerent (ꢀrom 0.2 equivalent to
2
6 equivalents) equivalents oꢀ NaHSO . As it can be seen
3
ꢀ
rom Fig. 2, the higher the equivalent oꢀ NaHSO was used,
selected as the optimized catalyst loading ꢀor chemoselective
3
the larger ratio oꢀ 3 in the product was obtained, the better
synthesis oꢀ 3.
chemoselectivity was given. It means that NaHSO plays an
3
important role in the chemoselectivity oꢀ the model reaction.
Eꢀect of the reaction temperature
When less than 0.6 equivalent oꢀ NaHSO was used as the
3
catalyst, the 3 was less than 4. Aꢀter that equivalent, prod-
The eꢁects oꢀ reaction temperature on the yields oꢀ model
reaction were investigated. The model reactions were car-
uct 3 was larger than 4. It can be seen ꢀrom Fig. 2, the ratio
oꢀ 3 to 4 was 40:60 when promoted by 0.2 eq oꢀ NaHSO ,
ried out in water (4.0 mL) in the presence oꢀ NaHSO
3
3
which was slightly larger than that obtained in pure water ꢀor
(11.0 eq) at diꢁerent temperature in 30 min. As shown
in Fig. 3, the higher the reaction temperature, the ꢀaster
the reaction rate, the higher the isolated yield oꢀ 3. At
30 °C, only 1% oꢀ 3 was obtained and the model reaction
could not ꢂnished in 24 h. When carried out at 40, 50,
60 and 70 °C, the reaction system was a slightly viscous
yellow mixture and the isolated yields were 5, 10, 60 and
70%, respectively. Unꢀortunately, trace amount oꢀ 4 could
be detected in the products. To our delight, when carried
out at 80, 90, and 100 °C, the model reaction proceeded
smoothly with the excellent yield oꢀ 3 and no 4 could be
detected in the products. It was mentioning that it took less
than 5 min to complete the model reaction at 100 °C. And
product 3. Increasing the equivalent oꢀ NaHSO to 0.6 eq,
3
almost the same amount oꢀ 3 and 4 were obtained. Continu-
ous increasing the equivalent oꢀ NaHSO to 1.0 eq, the ratio
3
oꢀ 3 to 4 reached to 70:30. Until increasing the equivalent
oꢀ NaHSO to 11.0 eq, the ratio oꢀ 3 to 4 reached to 100:0,
3
which indicated that enough equivalent oꢀ NaHSO was
3
needed ꢀor chemoselective synthesis oꢀ 3. Besides, prod-
uct 3 precipitated ꢀrom the system as a white solid. Further
increasing the equivalent oꢀ NaHSO to 26.0 eq (saturated
3
solution), the same result was obtained as that in the pres-
ence oꢀ 11.0 eq oꢀ NaHSO . Thereꢀore, 11.0 eq NaHSO was
3
3
1
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Chemical Papers
the relatively higher isolated yield (95%) was obtained
than that at 80 °C (93%) or 90 °C (92%). Thereꢀore, 100 °C
was selected as the optimized temperature.
The plausible mechanism of the model reaction
promoted by NaHSO3
The plausible mechanism ꢀor chemoselective synthesis oꢀ
2
-substituted benzimidazole 3 in the presence oꢀ NaHSO
3
in water is outlined in Fig. 4. Firstly, the aldehyde 1 quickly
reacted with NaHSO to ꢀorm the aldehyde bisulꢂte adduct
3
1
′, which reacted with 2 to ꢀorm the intermediate 2′ (Wells
et al. 2001; Neelakaktak and Hbrtung 1959). Aꢀter elimi-
nating oꢀ NaHSO , the intermediate 2′ was changed to the
3
important monoaldimine 3′, which had two transꢀormation
paths to ꢀorm diꢁerent product 3 or 4. One transꢀormation
path ꢀor 3′ was to ꢀorm 3 aꢀter a sequence oꢀ cyclization
and oxidation processes (Ridley et al. 1965; Lin and Yang
2
005; Du and Luo 2010). Another transꢀormation path ꢀor 3′
was to ꢀorm 4 aꢀter a sequence oꢀ addition, elimination and
1
,3-hydrogen shiꢀt rearrangement (Zhang et al. 2012; Wan
1
Fig. 5 H NMR spectra oꢀ benzaldehyde (a), benzaldehyde + 0.4 eq
et al. 2009; Kumar et al. 2013a, b). In the transꢀormation
NaHSO (b), benzaldehyde + 1.0 eq NaHSO (c), and aldehyde
3
3
bisulꢂte adduct (d)
processes, the NaHSO had two important roles in the abso-
3
lutely chemoselective ꢀormation oꢀ 2-substituted benzimi-
dazole 3. One role was to hamper ꢀormation oꢀ bisaldimine
6
′, which was the important intermediate ꢀor generating 4.
In addition, as shown in Fig. 5, one equivalent oꢀ NaHSO
3
As shown in Fig. 2, the ratio oꢀ 3 to 4 ꢀrom 32:68 (in the
was enough to completely transꢀorm aldehyde 1 into
the aldehyde bisulꢂte adduct 1′ in water. Another role oꢀ
absence oꢀ NaHSO ) changed to 70:30 (in the presence oꢀ
3
1
.0 eq NaHSO ). The increasing ratio oꢀ 3 in the product
NaHSO was served as oxidant (Sharma et al. 2015). During
3
3
indicated that the ꢀormation oꢀ bisaldimine 6′ ꢀrom inter-
mediate 3′ with aldehyde bisulꢂte adduct 1′ became more
difcult than directly reacting intermediate 3′ with aldehyde
the oxidation processes, both the oxygen in the air and the
NaHSO could be the oxidants. When the reaction between
3
aldehyde bisulꢂte adduct 1′ and 2 was carried out in pure
oxygen atmosphere, the ratio oꢀ 3 to 4 was only 85:15, which
was slightly higher than that in air (70:30). It indicated that
the oxidizability oꢀ oxygen was not enough. As we all know,
1. That was to say, aꢀter reacting aldehyde with NaHSO , the
3
reactivity oꢀ the ꢀormed aldehyde bisulꢂte adduct 1′ with the
monoaldimine 3′ decreased.
(
NH ) S O was a strong water soluble, nonhazardous and
4 2 2 8
Fig. 4 The plausible mechanism oꢀ the model reaction promoted by NaHSO3
1
3

Chemical Papers
relatively cheap oxidant (Austen and Kane 2001), which was
used ꢀor ꢀurther experiment. The reaction was carried out by
reacting oꢀ aldehyde bisulꢂte adduct 1′ with 2 in the pres-
ence oꢀ (NH ) S O (1.0 eq) at room temperature in 3 h.
Gram scale experiment
To ꢀurther veriꢀy the ꢀeasibility oꢀ the method, we repeated
the experiment on gram scale and adjusted the reaction con-
ditions in sight oꢀ a 20 g scale up. The reaction conditions
were as ꢀollow: benzaldehyde (100.0 mmol, 10.6 g), o-phe-
4
2
2
8
Surprisingly, a black reaction mixture quickly ꢀormed aꢀter
adding (NH ) S O and the product turned out to be exclu-
4
2
2
8
sive 3 as white solid aꢀter post-processing. The same result
nylenediamine (100.0 mmol, 10.8 g), NaHSO (11.0 eq)
3
was obtained by reacting oꢀ 1, NaHSO (1.0 eq) and 2 in
and water (400 mL) at 100 °C. The reaction was completed
in 5 min. Fortunately, the desired 2-phenylbenzimidazole
(18.2 g) was isolated in 94% yield and 99.0% HPLC purity
as an oꢁ-white solid. In comparison with the literature (Betti
et al. 2014), they obtained 2-substituted benzimidazole in
82% yield and 98% HPLC purity, which used aldehyde,
3
the presence oꢀ (NH ) S O (1.0 eq). However, when the
4
2
2
8
reaction was carried out by reacting oꢀ 1 and 2 merely in the
presence oꢀ (NH ) S O (1.0 eq), 3 and 4 were both obtained
4
2
2
8
in the ratio oꢀ 50:50. According to the results mentioned
above, the oxidation process determined the chemoselec-
tive synthesis oꢀ the 2-substituted benzimidazole and enough
oxidant was a crucial ꢀactor (Pino et al. 1996; Sharghi et al.
NaHSO and o-phenylenediamine as raw material with a
3
molar ratio oꢀ 1:1:1. Moreover, they employed water and
ethanol as mixed solvent and conducted the experiment at
70 °C ꢀor 3 h. Our established method has the advantage
oꢀ better chemoselectivity, higher yield, greener reaction
medium, simpler post-processing and shorter reaction time.
2
008; Zhu and Wei 2011; Bahrami et al. 2008). Thus, due to
the weak oxidizability oꢀ NaHSO , a great deal oꢀ NaHSO
3
3
(
more than 11.0 eq) and high reaction temperature were
needed in the protocol established in this paper ꢀor abso-
lutely chemoselective synthesis oꢀ 3.
Although more NaHSO in water was needed in our method,
3
we attempted to recycle NaHSO by recirculating the ꢂltrate.
3
Substrates extension
The product had a slight reduction in purity, which could
reach 98% in purity aꢀter ꢂve cycles.
Finally, with the optimal reaction conditions, the scope and
limitations oꢀ this methodology by varying aldehyde and
phenylenediamine were investigated. The results are pre-
sented in Table 1.
Characterization of compound
1
2‑Phenyl‑1H‑benzo[d]imidazole (3) White solid. H NMR
It was upliꢀting that not only aromatic aldehydes, but also
phenylenediamines with an electron-withdrawing group
or an electron-donating group aꢁorded excellent yields oꢀ
(DMSO-d , 600 MHz) δ: 12.91 (s, 1H), 8.19 (d, J = 7.6 Hz,
6
2H), 7.61–7.55 (m, 4H), 7.49–7.51 (m, 1H), 7.21–7.22 (m,
1
3
2H). C NMR (DMSO-d , 100 MHz) δ: 151.2, 143.8, 135.0,
6
2
-substituted benzimidazole derivatives. Similarly, the ali-
130.2, 129.8, 128.9, 126.4, 122.5, 121.6, 118.8, 111.3 (Li
phatic aldehydes also gave excellent yields oꢀ 2-substituted
benzimidazole derivatives. Another promising ꢀeature oꢀ
this methodology was that the products could be isolated
aꢀter simply ꢂltration. These advantages distinguished the
present methodology ꢀrom previously reported methods,
which required a large amount oꢀ organic solvents and time-
consuming tedious puriꢂcation processes.
et al. 2016; Peng et al. 2011).
2‑(2,4‑Dichlorophenyl)‑1H‑benzo[d]imidazole (5) White
1
solid. H NMR (DMSO-d , 600 MHz) δ: 12.77 (s, 1H),
6
7.95 (d, J = 8.4 Hz, 1H), 7.85 (s, 1H), 7.71 (d, J = 7.8 Hz,
1H), 7.62 (d, J = 8.4 Hz, 1H), 7.59–7.56 (m, 1H), 7.25 (dt,
1
3
J = 24.0, 7.0 Hz, 2H). C NMR (DMSO-d , 100 MHz)
6
Furthermore, we have also veriꢂed this methodology
by extending o-phenylenediamine with nine complicated
δ: 148.1, 143.1, 135.0, 134.6, 133.2, 132.6, 129.9, 128.8,
127.7, 122.9, 121.8, 119.1, 111.8 (Coppola 2008).
1
H-1,2,3-triazole-4-carbaldehyde derivatives (4a–4i),
which were synthesized in three steps ꢀrom aromatic amine
via diazo-reaction, chick chemistry and oxidation reaction
2‑(Furan‑2‑yl)‑1H‑benzo[d]imidazole (6) Pale yellow
solid. δ: 12.92 (s, 1H), 7.95 (d, J = 1.2 Hz, 1H), 7.62
(d, J = 6.4 Hz, 1H), 7.50 (d, J = 6.4 Hz, 1H), 7.20 (d,
(
Fig. 6). The results are presented in Table 2. As shown in
1
3
Table 2, the reaction could also proceed very well started
rom complex aldehydes, which had excellent yields, short
J = 3.6 Hz, 3H), 6.73–6.74 (m, 1H). C NMR (DMSO-d ,
6
ꢀ
100 MHz) δ: 145.6, 144.6, 143.6, 122.2, 112.3, 110.5 (Yu
reaction time and high chemoselectivity compared with tra-
ditional methods. Besides, we synthesized nine new 2-sub-
stituted benzimidazole derivatives containing a 1,2,3-tria-
zole moiety, which might possess signiꢂcant biological
activities.
and Lu 2015; Abdollahi-Alibeik and Hajihakimi 2013).
2‑(2‑Fluorophenyl)‑1H‑benzo[d]imidazole (7) White solid.
1
H NMR (DMSO-d , 400 MHz) δ: 12.60 (s, 1H), 8.24 (t,
6
J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.60–7.55 (m,
1
3
2
H), 7.48–7.38 (m, 2H), 7.27–7.20 (m, 2H). C NMR
(
DMSO-d , 100 MHz) δ: 160.7, 158.2, 146.3, 143.0, 135.0,
6
1
3

Chemical Papers
Table 1 Synthesis oꢀ benzimidazoles promoted by NaHSO in water at 100 °C
3
Time (min) Yield (%)b
phenylenediamine
Entry aldehyde
Product
3
5
6
7
8
9
5
95
92
91
92
92
86
92
95
91
94
89
94
95
92
90
90
92
91
89
15
15
10
10
20
20
15
15
15
20
15
10
25
20
25
20
25
40
10
11
12
13
14
15
16
17
18
19
20
21
22
CH CHO
3
1
3

Chemical Papers
Table 1 (continued)
Reaction conditions: aldehyde (1.0 mmol), phenylenediamines (1.0 mmol), NaHSO (11.0 mmol, 1.14 g) and water (4.0 mL) at 100 °C
3
a
Isolated yields
Fig. 6 Synthesis oꢀ 2-substi-
tuted benzimidazole derivatives
containing a 1,2,3-triazole
moiety
Table 2 Synthesis oꢀ 2-(1H-1,2,3-triazol-4-yl)-1H-benzo[d]imidazole derivatives promoted by NaHSO in water at 100 °C
3
Entry
aldehydes
Product
Time (min)
Yield (%) b
5
a
10
10
15
10
15
20
20
25
20
94
93
93
92
92
89
91
92
92
5b
5
c
5d
5
e
5
f
5g
5h
5
i
Reaction conditions: aldehyde (1.0 mmol), o-phenylenediamine (1.0 mmol, 108.1 mg), NaHSO (11.0 mmol, 1.14 g) and water (4.0 mL) at
3
1
00 °C
a
Isolated yields
1
3

Chemical Papers
1
1
1
31.8 (d, J = 9 Hz), 130.2, (d, J = 3 Hz), 125.0, 122.7,
21.8, 118.9, 118.0 (d, J = 12 Hz), 116.5 (d, J = 22 Hz),
11.9.
153.1, 151.1, 139.2, 132.6, 127.1, 123.9, 122.1, 120.3,
118.2, 114.4 (Aakeröy et al. 2007).
2
‑(4‑Methoxyphenyl)‑1H‑benzo[d]imidazole (15) White
1
2
‑(2‑Methoxyphenyl)‑1H‑benzo[d]imidazole (8) Oꢁ-white
solid. H NMR (DMSO-d , 600 MHz) δ: 12.75 (s, 1H), 8.12
6
1
solid. H NMR (DMSO-d , 600 MHz) δ: 12.12 (s, 1H), 8.34
(d, J = 8.7 Hz, 2H), 7.56 (br s, 2H), 7.18–7.17 (m, 2H), 7.12
6
1
3
(
d, J = 12.0 Hz, 1H), 7.64 (brs, 2H), 7.49 (t, J = 9.0 Hz,
(d, J = 8.7 Hz, 2H), 3.84 (s, 3H). C NMR (DMSO-d ,
6
1
H), 7.25 (d, J = 12.0 Hz, 1H), 7.20-7.19 (m, 2H), 7.13
600 MHz) δ: 161.1, 151.8, 128.5, 123.2, 122.3, 114.8, 55.8
1
3
(
t, J = 9.0 Hz, 1H), 4.04 (s, 3H). C NMR (DMSO-d ,
(Mahesh et al. 2015; Alapati et al. 2015).
6
1
00 MHz) δ: 156.7, 148.9, 131.2, 129.7, 121.7, 120.8, 118.1,
1
12.1, 55.7 (Alapati et al. 2015).
2‑(4‑Bromophenyl)‑1H‑benzo[d]imidazole (16) Light yel-
1
low solid. H NMR (DMSO-d , 600 MHz) δ: 12.99 (s, 1H),
6
4
‑(1H‑benzo[d]imidazol‑2‑yl)‑2‑methoxyphenol (9) White
8.12 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.67 (d,
1
solid. H NMR (DMSO-d , 600 MHz) δ: 12.65 (s, 1H), 9.52
J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.25–7.19 (m,
6
13
(
s, 1H), 7.75 (s, 1H), 7.62 (d, J = 8.1 Hz, 1H), 7.56 (brs,
2H). C NMR (DMSO-d , 100 MHz) δ: 150.2, 132.0, 129.4,
6
2
3
1
H), 7.16–7.15 (m, 2H), 6.92 (d, J = 8.2 Hz, 1H), 3.89 (s,
128.3, 123.2 (Wang et al. 2015).
13
H). C NMR (DMSO-d , 100 MHz) δ: 151.8, 148.2, 147.8,
6
1
21.6, 121.4, 119.6, 115.6, 110.3, 55.6 (Mao et al. 2010).
2‑Ethyl‑1H‑benzo[d]imidazole (17) Brown solid. H NMR
(
DMSO-d , 400 MHz) δ: 7.47–7.44 (m, 2H), 7.11–7.09 (m,
6
1
3
2
‑(1H‑benzo[d]imidazol‑2‑yl)phenol (10) White solid. 1H
2H), 2.83 (q, J = 7.6 Hz, 2H), 1.32 (t, J = 7.6 Hz, 3H).
C
NMR (DMSO-d , 400 MHz), δ 13.24 (br s, 1H), 13.18 (s,
NMR (DMSO-d , 150 MHz) δ: 156.6, 139.2, 121.5, 114.8,
6
6
1
7
2
H), 8.06 (dd, J = 7.8, 1.4 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H),
22.4, 12.7 (Kato et al. 2013).
.61 (d, J = 7.5 Hz, 1H), 7.41–7.37 (m, 1H), 7.33–7.25 (m,
1
3
1
H), 7.06–7.01 (m, 2H). C NMR (DMSO-d , 100 MHz)
2‑Benzyl‑1H‑benzo[d]imidazole (18) White solid. H NMR
6
δ: 158.0, 151.7, 140.8, 133.1, 131.7, 126.2, 123.2, 122.4,
(DMSO-d , 400 MHz) δ: 7.51–7.48 (m, 2H), 7.33–7.30 (m,
6
1
19.1, 117.9, 117.2, 112.6, 111.4 (Jain et al. 2013).
4H), 7.26–7.22 (m, 1H), 7.16–7.13 (m, 2H), 4.19 (s, 2H).
1
3
C NMR (DMSO-d , 150 MHz) δ: 153.9, 138.9, 137.9,
6
2
‑(Thiophen‑2‑yl)‑1H‑benzo[d]imidazole (11) Pale yellow
129.2, 129.0, 127.0, 122.0, 115.0, 35.3 (Nguyen et al. 2013).
1
solid. H NMR (DMSO-d , 400 MHz) δ: 12.96 (s, 1H),
6
1
7
.85 (d, J = 4.0 Hz, 1H), 7.74 (d, J = 4.0 Hz, 1H), 7.62 (d,
2‑Methyl‑1H‑benzo[d]imidazole (19) Yellow solid. H NMR
J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.25–7.16 (m,
(DMSO-d , 600 MHz) δ: 12.16 (s, 1H), 7.45–7.43 (m, 2H),
6
13
13
3
H). C NMR (DMSO-d , 100 MHz) δ: 147.0, 143.6, 134.7,
7.11–7.08 (m, 2H), 2.48 (s, 3H). C NMR (DMSO-d ,
6
6
1
33.7, 128.7, 128.3, 126.7, 122.6, 121.7, 118.5, 111.1 (Yong
150 MHz) δ: 151.7, 139.2, 121.5, 114.6, 15.10 (Sharma and
et al. 2012).
Gupta 2016).
2
‑(Pyridin‑3‑yl)‑1H‑benzo[d]imidazole (12) Light purple
2‑Isobutyl‑1H‑benzo[d]imidazole (20) Light yellow solid.
1
1
solid. H NMR (DMSO-d , 400 MHz) δ: 13.14 (s, 1H),
H NMR (DMSO-d , 600 MHz) δ: 7.47–7.45 (m, 2H), 7.12–
6
6
9
.37 (d, J = 1.6 Hz, 1H), 8.69 (d, J = 4.8 Hz, 1H), 8.51
7.09 (m, 2H), 2.68 (d, J = 7.3 Hz, 2H), 2.20–2.13 (m, 1H),
1
3
(
dt, J = 8.0, 1.9 Hz, 1H), 7.59–7.71 (m, 3H), 7.25–7.26 (m,
0.94 (d, J = 6.7 Hz, 6H). C NMR (DMSO-d , 150 MHz)
6
13
2
H). C NMR (DMSO-d , 100 MHz) δ: 150.5, 148.8, 147.5,
δ: 154.8, 139.3, 121.5, 114.9, 38.2, 28.2, 22.8 (Payne et al.
6
1
43.7, 134.9, 133.7, 126.1, 124.0, 122.9, 122.0, 119.1, 111.5
2010).
(
Kumar et al. 2010).
5
,6‑Dimethyl‑2‑phenyl‑1H‑benzo[d]imidazole (21) White
1
2
‑(Thiophen‑3‑yl)‑1H‑benzo[d]imidazole (13) Oꢀꢀ-white
solid. H NMR (DMSO-d , 600 MHz) δ: 12.67 (s, 1H),
6
1
solid. H NMR (DMSO-d , 600 MHz) δ: 12.78 (s, 1H), 8.24
8.13 (d, J = 7.3 Hz, 2H), 7.53 (t, J = 7.4 Hz, 2H), 7.47 (t,
6
(
br s, 1H), 7.79–7.78 (m, 1H), 7.74–7.72 (m, 1H), 7.62–7.51
J = 7.3 Hz, 1H), 7.43 (brs, 1H), 7.30 (brs, 1H), 2.33 (s,
13
13
(
m, 2H), 7.19 (br s, 2H). C NMR (DMSO-d , 100 MHz) δ:
6H). C NMR (DMSO-d , 100 MHz) δ: 150.3, 142.5, 133.5,
6
6
1
48.0, 132.5, 127.6, 126.3, 124.9, 121.9 (Düꢀert et al. 2013).
131.1, 130.4, 129.9, 129.5, 128.8, 126.1, 118.9, 111.3, 20.0
(
Naresh et al. 2014).
2
‑(Pyridin‑4‑yl)‑1H‑benzo[d]imidazole (14) White solid.
1
H NMR (DMSO-d , 600 MHz) δ: 13.27 (s, 1H), 8.77 (d,
5‑Nitro‑2‑phenyl‑1H‑benzo[d]imidazole (22) Light yel-
6
1
J = 5.1 Hz, 2H), 8.11 (d, J = 5.3 Hz, 2H), 7.73–7.62 (m,
low solid. H NMR (DMSO-d , 600 MHz) δ: 8.49 (s, 1H),
6
13
2
H), 7.28 (br s, 2H). C NMR (CD OD, 100 MHz) δ: 159.5,
8.23 (d, J = 6.8 Hz, 2H), 8.14 (d, J = 8.7 Hz, 1H), 7.78 (d,
3
1
3

Chemical Papers
1
3
13
J = 8.8 Hz, 1H), 7.62–7.58 (m, 3H). C NMR (DMSO-d ,
J = 7.6 Hz, 1H), 7.27–7.21 (m, 2H); C NMR (150 MHz,
6
1
00 MHz) δ: 155.8, 142.6, 130.9, 129.1, 129.0, 126.9, 117.9.
DMSO-d ) δ: 155.4, 153.7, 144.3, 144.1, 140.4, 134.9, 132.2
6
(
Naresh et al. 2014).
(d, J = 7.5 Hz, CH), 126.7, 126.1, 125.0 (d, J = 10.5 Hz,
CH), 123.2, 122.3, 119.3, 117.7 (d, J = 19.5 Hz, CH), 112.2;
ESI-HRMS: m/z Calcd ꢀor C H FN + H: 280.0993, ꢀound
2
(
‑(1‑Phenyl‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]imidazole
15
11
5
−
1
5a) White solid, m.p. > 270 °C; IR (KBr) (νmax cm ):
280.1025.
3
1
1
123, 1683, 1597, 1507, 1453, 1401, 1331, 1300, 1054,
1
043, 759, 685, 669; H NMR (600 MHz, DMSO-d ) δ:
2‑(1‑(4‑Bromophenyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]
6
3.23 (s, 1H), 9.53 (s, 1H), 8.06 (d, J = 7.9 Hz, 2H), 7.66 (t,
imidazole (5f) White solid, m.p. > 270 °C; IR (KBr)
−
1
J = 7.9 Hz, 3H), 7.56 (t, J = 7.3 Hz, 2H), 7.24–7.24 (m, 2H);
(ν
cm ): 3125, 1680, 1593, 1500, 1423, 1402, 1326,
max
1
3
1
C NMR (150 MHz, DMSO-d ) δ: 144.5, 144.1, 140.9,
1229, 1052, 989, 827, 733; H NMR (600 MHz, DMSO-
6
1
1
2
36.8, 134.9, 130.4, 129.6, 123.2, 122.8, 122.3, 120.8,
d ) δ: 9.56 (s, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.86 (d,
6
1
3
19.2, 112.2; ESI-HRMS: m/z Calcd ꢀor C H N + H:
J = 8.7 Hz, 2H), 7.62–7.61 (m, 2H), 7.26–7.23 (m, 2H);
C
1
5
12
5
62.1087, ꢀound 262.1100.
NMR (150 MHz, DMSO-d ) δ: 144.2, 140.9, 136.0, 133.3,
6
1
23.0, 122.9, 122.8, 122.3, 115.8; ESI-HRMS: m/z Calcd ꢀor
2
(
‑(1‑(p‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]imidazole
C H BrN + H: 340.0192, ꢀound 340.0200.
1
5
11
5
−
1
5b) White solid, m.p. > 270 °C; IR (KBr) (νmax cm ):
3
9
1
137, 3107, 1519, 1452, 1401, 1355, 1328, 1043, 993,
2 ‑ ( 1 ‑ ( 2 ‑ M e t h y l ‑ 3 ‑ n i t r o p h e n y l ) ‑ 1 H ‑ 1 , 2 , 3 ‑ t r i a ‑
1
47, 825, 748; H NMR (600 MHz, DMSO-d ) δ: 9.47 (s,
zol‑4‑yl)‑1H‑benzo[d]imidazole (5g) White solid, m.p.
6
−
1
H), 7.92 (d, J = 8.3 Hz, 2H), 7.62–7.61 (m, 2H), 7.45 (d,
> 270 °C; IR (KBr) (ν
cm ): 3117, 1649, 1584, 1474,
max
1
3
1
J = 8.2 Hz, 2H), 7.25–7.23 (m, 2H), 2.41 (s, 3H); C NMR
1454, 1402, 1228, 1187, 1040, 894, 746, 619; H NMR
(
150 MHz, DMSO-d ) δ: 144.4, 140.6, 139.3, 134.6, 130.8,
(600 MHz, DMSO-d ) δ: 9.07 (s, 1H), 7.70–7.69 (m,
6
6
1
22.8, 122.7, 120.7, 115.6, 21.1; ESI-HRMS: m/z Calcd ꢀor
2H), 7.36–7.35 (m, 2H), 7.14 (t, J = 7.9 Hz, 1H), 6.91 (d,
1
3
C H N + H: 276.1244, ꢀound 276.1265.
J = 8.1 Hz, 1H), 6.72 (d, J = 7.6 Hz, 1H), 1.86 (s, 3H);
C
1
6
14
5
NMR (150 MHz, DMSO-d ) δ: 148.2, 143.7, 137.5, 136.9,
6
2
‑(1‑(3‑Chlorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]
136.7, 127.4, 127.2, 124.0, 117.3, 116.3, 115.3, 114.4, 12.4;
imidazole (5c) White solid, m.p. 220–222 °C;IR (KBr)
ESI-HRMS: m/z Calcd ꢀor C H N O + H: 321.1095,
1
6
13
6
2
−
1
(
ν
cm ): 3126, 1594, 1489, 1430, 1400, 1052, 774,
ꢀound 321.1107.
max
1
7
1
7
30, 676; H NMR (600 MHz, DMSO-d ) δ:13.25 (s,
6
H), 9.61 (s, 1H), 8.20 (s, 1H), 8.07 (d, J = 7.9 Hz, 1H),
2‑(1‑(4‑Iodophenyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]imi‑
.68 (t, J = 7.9 Hz, 2H), 7.63 (d, J = 7.9 Hz, 1H), 7.55 (d,
dazole (5h) Light yellow solid, m.p. > 270 °C; IR (KBr)
1
3
−1
J = 7.3 Hz, 1H), 7.26–7.22 (m, 2H); C NMR (150 MHz,
(ν
cm ): 3139, 3108, 1586, 1493, 1451, 1409, 1355,
max
1
DMSO-d ) δ: 144.3, 141.1, 137.9, 134.7, 132.1, 129.4,
1325, 1298, 1229, 1149, 1041, 989, 946, 826, 746; H
6
1
23.1, 122.3, 120.7, 119.5, 119.2, 112.2; ESI-HRMS: m/z
NMR (400 MHz, DMSO-d ) δ: 13.21 (s, 1H), 9.54 (s, 1H),
6
Calcd ꢀor C H ClN + H: 296.0697, ꢀound 296.0714.
8.03–7.99 (m, 2H), 7.90–7.85 (m, 2H), 7.61 (m, 2H), 7.26–
1
5
11
5
1
3
7
.21 (m, 2H); C NMR (100 MHz, DMSO-d ) δ: 143.8,
6
2
(
‑(1‑(o‑Tolyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]imidazole
140.5, 138.6, 136.0, 122.3, 94.9; ESI-HRMS: m/z Calcd ꢀor
−
1
5d) White solid, m.p. > 270 °C; IR (KBr) (νmax cm ):
C H IN + H: 388.0054, ꢀound 388.0080.
15
11
5
3
194, 1682, 1584, 1503, 1456, 1402, 1357, 1325, 1302,
1
1
057, 991, 764, 736, 710; H NMR (600 MHz, DMSO-d )
Methyl 4‑((4‑(1H‑benzo[d]imidazol‑2‑yl)‑1H‑1,2,3‑tria‑
6
δ:13.20 (s, 1H), 9.16 (s, 1H), 7.61–7.53 (m, 5H), 7.48–
zol‑1‑yl)methyl)benzoate (5i) White solid, m.p. > 270 °C;
1
3
−1
7
.46 (m, 1H), 7.24–7.22 (m, 2H), 2.24 (s, 3H); C NMR
IR (KBr) (ν cm ): 3137, 2925, 1719, 1398, 1325, 1279,
max
1
(
150 MHz, DMSO-d ) δ: 144.6, 140.0, 136.4, 133.7, 131.9,
1111, 1054, 1023, 953, 741; H NMR (400 MHz, DMSO-
6
1
30.6, 127.5, 126.7, 126.2, 122.7, 17.9; ESI-HRMS: m/z
d ) δ: 13.10 (s, 1H), 8.90 (s, 1H), 7.80 (d, J = 7.5 Hz, 2H),
6
Calcd ꢀor C H N + H: 276.1244, ꢀound 276.1256.
7.63 (d, J = 7.5 Hz, 1H), 7.51 (d, J = 7.5 Hz, 3H), 7.24–7.17
1
6
14
5
1
3
(
m, 2H), 5.85 (s, 2H), 3.85 (s, 3H); C NMR (100 MHz,
2
‑(1‑(2‑Fluorophenyl)‑1H‑1,2,3‑triazol‑4‑yl)‑1H‑benzo[d]
DMSO-d ) δ: 165.8, 144.3, 143.5, 140.9, 139.7, 134.3,
6
imidazole (5e) White solid, m.p. > 270 °C; IR (KBr)
129.6, 129.4, 128.1, 124.6, 122.5, 121.6, 118.6, 111.5, 52.6,
−
1
(
ν
1
1
cm ): 3232, 3191, 3024, 1594, 1511, 1496, 1474,
52.2; ESI-HRMS: m/z Calcd ꢀor C H N O + H: 334.1299,
max
18 16
5
2
450, 1431, 1357, 1299, 1268, 1238, 1216, 1112, 1045,
ꢀound 334.1328.
1
014, 991, 943, 825, 765, 747, 669; H NMR (600 MHz,
DMSO-d ) δ: 13.25 (s, 1H), 9.26 (s, 1H), 7.97 (t, J = 8.3 Hz,
6
1
H), 7.70–7.62 (m, 3H), 7.56 (d, J = 7.7 Hz, 1H), 7.50 (t,
1
3

Chemical Papers
inhibitor oꢀ NF-ҡB. Bioorg Med Chem 24:1872–1878. https://
doi.org/10.1016/j.bmc.2016.03.012
Conclusions
Bouwman E, Driessen WL, Reedjik J (1990) Model systems ꢀor type
I copper proteins: structures oꢀ copper coordination compounds
with thioether and azole-containing ligands. Coord Chem Rev
In summary, we developed an efcient, green and simple
protocol ꢀor the chemoselective synthesis oꢀ 2-arylbenzami-
1
04:143–172. https://doi.org/10.1016/0010-8545(90)80042-R
dazoles in water at 100 °C promoted by NaHSO . The estab-
3
Chen GF, Shen HD, Jia HM, Zhang LY, Kang HY, Qi QQ, Chen BH,
Cao JL, Li JT (2013) Eco-ꢀriendly synthesis oꢀ 2-substituted ben-
zimidazoles using air as the oxidant. Aust J Chem 66:262–266.
https://doi.org/10.1071/CH12458
lished protocol has the advantages oꢀ short reaction time,
simple and clean work-up procedure, high yields and broad
substrates scope.
Coppola GM (2008) N-Hydroxyphthalimide/cobalt acetate, a
new catalytic oxidative system ꢀor the synthesis oꢀ ben-
zimidazoles. Synth Commun 38:3500–3507. https://doi.
org/10.1080/00397910802162959
Acknowledgements This work was supported ꢂnancially by Inno-
vative Talents Program oꢀ Henan Province (Nos. 164100510015,
1
74100510025 and 18A150030), Foundation oꢀ Henan Educational
Dandia A, Parewa V, Rathore KS (2012) Synthesis and characteriza-
tion oꢀ CdS and Mn doped CdS nanoparticles and their catalytic
application ꢀor chemoselective synthesis oꢀ benzimidazoles and
benzothiazoles in aqueous medium. Catal Commun 28:90–94.
https://doi.org/10.1016/j.catcom.2012.08.020
Committee (Nos. 15A150054 and 16A350015), Scientiꢂc Research
Foundation ꢀor Doctors (No. qd16106) and Youth Foundation (No.
2
016QK09) oꢀ Henan Normal University.
Du LH, Luo XP (2010) Efcient one-pot synthesis oꢀ benzimidazoles
under solvent-ꢀree conditions. Synth Commun 40:2880–2886.
https://doi.org/10.1080/00397910903340629
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