Efficient aerobic oxidative synthesis of benzimidazoles with Fe(III) based PEG1000 dicationic imidazolium ionic liquid/toluene temperature-dependent biphasic system

Article abstract of DOI:10.1002/jccs.201400298

A green protocol for the synthesis of benzimidazoles with Fe(III) based PEG₁₀₀₀ dicationic imidazolium ionic liquid ([PEG₁₀₀₀mim₂][FeCl₄]₂)/toluene temperature-dependent biphasic system was described. Conformed by IR analysis, FeCl₄-is the dominating anion species. It could be seen that aldehydes arylamines and aromatic aldehydes bearing electron-deficient group (-Cl,-Br,-NO₂) and electron-rich groups(-OH, -N(CH₃)₂) on the aromatic rings gave good yields (78-96%). Moreover, the Fe(III) based PEG₁₀₀₀ dicationic imidazolium ionic liquid could be recycled and reused without significant loss of catalytic activity after seven runs.

Full text of DOI:10.1002/jccs.201400298

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Communication
Efficient Aerobic Oxidative Synthesis of Benzimidazoles with Fe(III) based PEG1000
Dicationic Imidazolium Ionic Liquid/toluene Temperature-dependent Biphasic System
Zhao-gang Wang,# Yong-gen Xia,# Yong Jin# and Ming Lu*
School of Chemical Engineering, Nanjing University of Science and Technology, Xiaolingwei 200, Nanjing, 210094,
P. R. China
(Received: Jul. 15, 2014; Accepted: Sept. 22, 2014; Published Online: ??; DOI: 10.1002/jccs.201400298)
A green protocol for the synthesis of benzimidazoles with Fe(III) based PEG1000 dicationic imidazolium
ionic liquid ([PEG1000mim2][FeCl4]2)/toluene temperature-dependent biphasic system was described.
-
Conformed by IR analysis, FeCl4 is the dominating anion species. It could be seen that aldehydes aryla-
mines and aromatic aldehydes bearing electron-deficient group (-Cl,-Br,-NO2) and electron-rich
groups(-OH, -N(CH3)2) on the aromatic rings gave good yields (78-96%). Moreover, the Fe(III) based
PEG1000 dicationic imidazolium ionic liquid could be recycled and reused without significant loss of cata-
lytic activity after seven runs.
Keywords: Fe(III) based PEG1000 dicationic imidazolium ionic liquid; Temperature-dependent
biphasic system; Benzimidazoles.
INTRODUCTION
Benzimidazoles are very useful compounds in the de-
safe and environmentally benign solvent, has droawn in-
creasing attention over the last decades due to its excellent
advantages such as negligible volatility, thermal stability,
remarkable solubility and a variety of available structures.3
Notably, functionalized ILs containing transition metals
for specific-task have attracted many researches in the syn-
thesis and application field. In particular, Fe(III) based
ILs,4 which combines the attractive properties of both mag-
netic ionic liquid and lewis acid, has been reported as a suc-
cessful and reusable catalyst in many organic reactions
such as hydroxymethylation5 and Friedel-Crafts reaction6
due to its non-pollutant feature from a standpoint of sus-
tainable chemistry and extraordinary durability for air prior
to other transition metals.
velopment of pharmaceutical industry, which exhibits sig-
nificant biological activity against several viruses1 such as
HIV, HSV-1, influenza, and human cytomegalovirus
(HCMV). In addition, benzimidazoles are very important
intermediates in organic synthesis. Although many meth-
ods have been reported for benzimidazole synthesis, there
are two general methods for the synthesis of benzimida-
zoles. One is the condensation of carboxylic compounds or
derivative (nitrile, imidate, orthoester) with o-phenylene-
diamines, which is usually performed under strong acidic
conditions, high temperatures, or microwave irradiation.
The other is the oxidative dehydrogenation of schiff bases,
which is often generated from the condensation of diamine
and aldehydes. Various oxidants2 such as DDQ, FeCl3,
MnO2, H2O2, Pb(OAc)4, Oxone, PhI(OAc)2, and
Na2S2O5K4[Fe(CN)6] have been employed in the reaction.
These methods are effective, however, in view of the im-
portance of green chemistry, the isolation of the products
and the recovery of catalysts hinder the development of
these systems. Therefore, developing a recyclable oxida-
tive system would be promising from catalytic efficiency
and sustainable development, exhibiting very appealing
prospects in view of green chemistry.
Besides, ionic liquids have also been designed for
bearing long alkyl chain affording properties of tempera-
ture-dependent phase behavior.7 Recently, Zhi and Hu8
have described a new class of polyethylene glycol based
dicationic ionic liquid (PEG1000 DIL), which exhibits a
temperature-dependent phase behavior with some organic
solvents (toluene or methylcyclohexane) and promotes re-
action efficiently. The polyethylene glycol based dicationic
ionic liquid shows good compatibility of the tandem cata-
lyst/substrate and the ideal green catalytic process of “one-
phase catalysis and two-phase separation” was achieved
because the reactants were miscible with the PEG based
Room temperature ionic liquids (RTILS), usually as a
* Corresponding author. Email: luming302@126.com
# Co-authors contributed equally to the work
Supporting information for this article is available on the www under http://dx.doi.org/10.1002/jccs.201400298
J. Chin. Chem. Soc. 2014, 61, 000-000
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1

Communication
Wang et al.
ILs at the experimental conditions, while the miscibility of
the products and the PEG based ILs was extremely poor
when cooled to room temperature.
the experiments for the synthesis of 2-phenyl benzimida-
zole, which was selected as a representative example, with
o-phenylenediamines and benzaldehyde as model sub-
strates. As expected, the desired target product was ob-
tained with lower yield when only Fe(III) or PEG1000
dicationic imidazolium ionic liquid was used for the reac-
tion (Table1, entry 1-2). When Fe(III) based PEG1000 di-
cationic imidazolium ionic liquid ([PEG1000mim2][FeCl4]2)
were employed to catalyze the reaction, to our delight, it
was clear that the catalytic system performed well to give
the desired product up to yield 96%. Also, a modest cata-
lyst amount of 5 mol% [PEG1000mim2][FeCl4]2 (10 mol%
FeCl3) provided the best results of the reaction in terms of
reaction yield and economy of catalyst charge (Table 1, en-
tries 3-5). Further experiments showed that the iron with
chloride is critical to the reaction which proved to be supe-
rior to nitrate and sulfate (Table 1, entries 6-7). The control
experiments showed that 80 °C is appropriate in consider-
ation of the reaction yield and catalytic activity of
[PEG1000mim2][FeCl4]2 (Table 1, entries 8-11). To investi-
gate the efficiency of the catalytic system, some commer-
cial organic solvents was then used as the reaction media
(Table 1, entry 2 and entries 12-15). As expected, the best
transformation was observed in Fe(III) based PEG1000
dicationic ionic, revealing this ionic liquid played an im-
portant role in the reaction process with the significant cat-
alytic performance for promotion of reaction. Also, the
product and Fe(III) based PEG1000 dicationic imidazolium
ionic liquid was easily separated after reaction due to the
As part of our continuous efforts to search for envi-
ronmentally benign protocols for transition metal catalytic
transformations, hererin, we report an efficient method for
synthesis of benzimidazoles from aryldiamines with aro-
matic aldehydes catalyzed by Fe(III) based PEG1000 dica-
tionic imidazolium ionic liquid ([PEG1000mim2][FeCl4]2),
which assembles the attractive properties of temperature-
dependent phase behavior and Fe(III) based ILs. It was de-
lighted to learn that the catalytic system in this paper could
afford high catalytic activity and excellent durability.
Moreover, the Fe(III) based PEG1000 dicationic imida-
zolium ionic liquid could be successfully recovered by
magnet force and be reused without significant loss of cata-
lytic activity. The protocol presented here provides an effi-
cacious strategy to achieve both high efficiency and cata-
lysts recycling from a viewpoint of green chemistry.
RESULTS AND DISCUSSSION
The Fe(III) based PEG1000 dicationic imidazolium
ionic liquid are comprised of PEG1000 supported diimida-
-
zolium cation and anions FeCl4 as depicted in Scheme 1.
This ionic liquid was easily prepared from commercially
available FeCl3 and PEG supported imidazolium salt. The
-
literature results indicated that FeCl4 is the dominating an-
ion species.9
Fe(III)-based PEG1000 diimidazolium cation
Ils
Scheme 1
To test this kind of metal-containing lewis acidic ILs,
acetonitrile was used as a basic probe molecule (Lewis
base) to determine the acidity of the iron-containing ILs
based on the reported principles. As can be seen in Fig. 1,
acetonitrile itself shows two characteristic C-N stretching
vibrations at 2252 and 2292 cm-1 (Fig. 1a). When aceto-
nitrile was mixed with the iron-containing IL, a third band
appeared at around 2354 cm-1 (Fig. 1c), indicating Lewis
acid-base interactions between the iron-containing ILs and
acetonitrile.
Fig. 1. IR spectra (a) acetonitrile; (b) Fe(III) based
PEG1000 dicationic imidazolium ionic liquid;
(c) mixtures of acetonitrile and Fe(III) based
PEG1000 dicationic imidazolium ionic liquid.
To investigate the catalytic system, we commenced
2
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J. Chin. Chem. Soc. 2014, 61, 000-000

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
A Green Protocol for Synthesis of Benzimidazoles
Table 1. Influence of reaction conditions on the synthesis of 2-
phenyl benzimidazolesa
Table 2. Synthesis of benzimidazoles from aldehydes and
diamines a
NH2
+
O
Fe(III) based PEG1000DIL
80¡æ
N
Fe(III) salts
(mol%)
Temprature Yeildb
Entry
Solvents
R2
R1
R1
(°C)
(%)
H
R2
N
H
X
NH2
X
1
-
biphasic system
toluene
80
80
45
62
76
96
93
90
80
82
38
52
65
79
75
84
80
85
Yieldsb
(%)
2
FeCl3 (5)
FeCl3 (5)
FeCl3 (10)
FeCl3 (20)
FeCl3 (40)
Entry
X
R1
R2
Time (h)
3
biphasic system
biphasic system
biphasic system
biphasic system
80
4
80
1
H
H
H
H
H
H
H
H
H
H
N
H
H
H
H
H
H
H
H
Ph
7
9
96
86
80
91
95
93
96
94
84
85
78
5
80
2
4-OHC6H4
4-Me2NC6H4
2-ClC6H4
6
80
3
10
6
7
Fe(SO4)3 (10) biphasic system
Fe(NO3)3 (10) biphasic system
80
4
8
80
5
4-ClC6H4
4.5
5
9
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
FeCl3 (10)
biphasic system
biphasic system
biphasic system
biphasic system
Ethanol
rt
6
4-BrC6H4
2, 4-ClC6H3
3-NO2C6H4
10
11
12
13
14
15
16
40
7
4
60
8
5
100
reflux
80
9
4-NO2
Ph
Hc
H
10
8
10
11
H
H
DMF
10
DMSO
80
Reaction conditions: [a] o-phenylenediamines 1.08 g (10 mmol)
and aldehyde1.06 g (10 mmol), [PEG1000mim2][FeCl4]2 (0.5
mmol), toluene (4 ml), 80 °C. [b] Products were purified by silica
gel column chromatography and confirmed by HPLC, 1H NMR,
Elemental analysis and melting point.
CH3CN
80
Reaction conditions: [a] o-phenylenediamines 1.08 g (10 mmol)
and benzaldehyde 1.06 g (10 mmol), [PEG1000mim2][FeCl4]2 (0.5
mmol), toluene (4 mL), 80 °C. [b]Yield of isolated product.
unique property “one-phase at high temperature and two-
phase at low temperature”.
jected to a subsequent run of the reaction by charging fresh
substrate. In a test of seven cycles, the Fe(III) based
PEG1000 dicationic imidazolium ionic liquid could be re-
used without significant loss of catalytic activity (Fig. 2).
The mechanism for the synthesis of benzimidazoles
from aromatic diamines and aldehydes was shown in
Scheme 2. The first step was dehydrated to form a schiff
base. During the next step, ring closure leaded to a five-
member ring and dehydrogenated with molecular oxygen
After establishing previous optimal conditions, we
continued to study the scope of the reaction with a series of
structurally variable arylamines and aromatic aldehydes. In
most cases, o-phenylenediamine reacted with various benz-
aldehyde smoothly to give the corresponding products. It
could be seen that aldehydes bearing electron-deficient
group (-Cl, -Br, -NO2) on the aromatic rings gave higher
yields of products than those bearing electron-rich groups
(-OH, -N(CH3)2) (Table 2, entries 2-8). Moreover, the rea-
son why aromatic aldehydes acted faster with o-phenylene-
diamine than aliphatic aldehydes was probably due to the
conjugated effect of phenyl group of benzaldehyde (Table
2, entry 1 and entry 10). On the other hand, diamine bearing
electron-deficient group on the aromatic rings (4-nitro-o-
phenylenediamine) or containing heterocycle (2,3-diami-
nopyridine) proceeded more inefficiently than o-phenyl-
enediamine in term of longer reaction time and lower yeild
(Table 2, entry 1, entry 9 and entry 11).
The reuse of Fe(III) based PEG1000 dicationic imida-
zolium ionic liquid was investigated by using o-phenylene-
diamine and benzaldehyde as a model reaction. The prod-
uct could be simply separated by decantation from the reac-
tion mixture while the ionic liquid phase was then sub-
Fig. 2. Cycling reaction of Fe(III) based PEG1000 di-
cationic imidazolium ionic liquid.
J. Chin. Chem. Soc. 2014, 61, 000-000
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Wang et al.
The mechanism for synthesis of benzimida-
7.54 (m, 4H, Ar-H), 7.21-7.20 (s, 2H, Ar-H); 13C NMR (125 MHz,
DMSO-d6): d = 38.99, 39.16, 39.32, 39.49, 39.65, 39.82, 39.99,
111.35, 122.48, 126.43, 128.97, 129.86, 130.15, 151.22; MS
(ESI): m/z = 193 [M-1+] 195 [M+1+]; Elemental analysis % Calcd
for C13H10N2: C 80.41; H 5.16; N 14.43. Found: C 80.46; H 5.12;
N 14.42.
Scheme 2
zole
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CONCLUSIONS
We have developed a green and efficient method for
the synthesis of benzimidazole catalyzed by Fe(III) based
PEG1000 dicationic imidazolium ionic liquid with excellent
yields. Owing to its high efficiency and good compatibility
of Fe(III) based PEG1000 dicationic imidazolium ionic liq-
uid, the catalytic system had a good catalytic performance
to promote reaction effectively. Moreover, it could be recy-
cled and reused without significant loss of catalytic activity
after seven runs. This environmentally catalytic system
would find a wider application in various reactions, which
is an ongoing project.
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EXPERIMENTAL
o-Phenylenediamines 1.08 g (10 mmol) and benaldehyde
1.06 g (10 mmol) were thoroughly mixed in Fe(III) based PEG1000
dicationic imidazolium ionic liquid/toluene (5 mL), the reaction
mixture was stirred at 80 °C and monitorted by TLC. After com-
pletion of the reaction, the reaction mixture was extracted with
ether, dried by anhydrous sodium sulfate and rotary evaporated,
the residue was purified by silica gel chromatography (n-hexane:
EtOAc = 10:1) gave the 2-phenyl benzimidazole (96% yield) with
spectral data consistent with the assigned structures for the prod-
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2-Phenyl-1H-Benzimidazole: White solid; mp 293~294
°C (from Ethanol) (lit,1 292~293 °C); Chroatography (n-hexane:
ethyl acetate = 10:1); 1H NMR dH (500 MHz, DMSO-d6): 12.93
(s, 1H, N-H), 8.19-8.18 (d, 2H, Ar-H), 7.67 (s, 1H, Ar-H), 7.56-
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4
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© 2014 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2014, 61, 000-000