Iron(III)–salen complex on a polymer scaffold as heterogeneous catalyst for synthesis of benzimidazoles

Article abstract of DOI:10.1007/s11164-018-3595-6

Benzimidazoles are important bioactive compounds with diverse applications in the medicinal, industrial, as well as agrochemical fields. In this study, an iron–salen complex on a polymer scaffold was synthesized and characterized, and its performance asse

Full text of DOI:10.1007/s11164-018-3595-6

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-3595-6(0123456789(). -, vo Vl
)
(
0
1
2
3
4
5
6
7
8
9
(
)
.
-
,
v
o
l
V
)
Iron(III)–salen complex on a polymer scaffold
as heterogeneous catalyst for synthesis of benzimidazoles
1 •
1 •
Kamlesh Rudreshwar Balinge Sagar Krushnarao Datir
1
1
•
Vijay Baburao Khajone
•
Karan Jivanlal Bhansali
1
1
Avinash Ganesh Khiratkar
•
Pundlik Rambhau Bhagat
Received: 2 August 2018 / Accepted: 10 September 2018
Ó Springer Nature B.V. 2018
Abstract
Benzimidazoles are important bioactive compounds with diverse applications in the
medicinal, industrial, as well as agrochemical fields. In this study, an iron–salen
complex on a polymer scaffold was synthesized and characterized, and its perfor-
mance assessed as a heterogeneous catalyst for synthesis of benzimidazoles. For-
mation of the metal complex was well confirmed by Fourier-transform infrared
spectroscopy (FT-IR) analysis, and the surface morphology and elemental compo-
sition was verified by scanning electron microscopy and energy-dispersive X-ray
spectroscopy, respectively. The surface area and pore size distribution were deter-
mined by Brunauer–Emmett–Teller analysis, and the high thermal stability of the
catalyst was revealed by thermogravimetric analysis. Its general potential for syn-
thesis of benzimidazoles from o-phenylenediamine with aldehydes containing
various electron-withdrawing and electron-donating substituents was confirmed.
The effects of different solvents, catalyst loadings, temperatures, and reaction
durations were also studied. The present protocol is found to be beneficial in terms
of excellent yield, adequate reaction time, and simple workup. Also, hot filtration
tests confirmed that the catalyst was truly heterogeneous and could be readily
recycled and reused several times, making this protocol attractive, commercial, and
environmentally friendly.
Keywords Polymer scaffold–Fe–salen Á Heterogeneous catalyst Á Benzimidazole
synthesis Á Thermally stable
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11164-
018-3595-6) contains supplementary material, which is available to authorized users.
&
Pundlik Rambhau Bhagat
drprbhagat111@gmail.com
1
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology,
Vellore 632 014, India
123

K. R. Balinge et al.
Introduction
Benzimidazole derivatives have been revealed as pharmaceutically significant
compounds that exhibit comparatively high biological activities, e.g., antifungal,
antiviral, and antihypertension properties [1]. The best apparent benzimidazole
complex in Nature is N-ribosyldimethylbenzimidazole, which acts as an essential
ligand for cobalt in vitamin B12 [2]. Beside their use as market drugs such as
telmisartan and dexlansoprazole, benzimidazoles are privileged scaffold structures
that show a wide spectrum of biological activity, e.g., as antiulcer, antitumor, anti-
human immunodeficiency virus (HIV), and antihistaminic agents as well as
veterinary medicines [3–5]. In addition, benzimidazoles are essential intermediates
in synthesis of dyes and polymers [6, 7] and also find common uses in corrosion
science [8], chemosensing [9], and fluorescence [10]. Due to their widespread use in
various fields of science and technology, a number of procedures have been
described for their synthesis. They are usually obtained by condensation of aromatic
1
,2-diamine with aldehydes [11], using oxidants or carboxylic acid derivatives.
To achieve mild reaction conditions and improve the yield of benzimidazoles, a
variety of homogeneous systems have been reported. Homogeneous catalytic
systems based on oxidants include H O with ceric ammonium nitrate (CAN) for
synthesis of 2-arylbenzimidazoles [12], PhI(OAc) /(2,2,6,6-tetramethylpiperidin-1-
2
2
2
yl)oxyl (TEMPO) for synthesis of multisubstituted benzimidazoles via iodine-
promoted oxidation reaction [13], iodobenzene for synthesis of 1,2-disubstituted
benzimidazoles with meta-chloroperoxybenzoic acid (mCPBA) as terminal oxidant
[
14], hypervalent iodine as oxidant [15], potassium salt of peroxymonosulfuric acid
oxone) [16], and TEMPO with air for synthesis of benzimidazoles [17]. Copper
(
halide or oxide catalytic systems used for synthesis of benzimidazoles include CuI
with ligand [18], CuI/tetramethylethylenediamine (TMEDA) [19], CuI/trimethylsi-
lyl azide (TMSN )/tert-butyl hydroperoxide (TBHP) [20], CuO/1,2-
3
dimethylethylenediamine (DMEDA) [21], CuOAc /TBHB [22], and Cu(OTF)
2
2
[
23]. Cu systems with amino acids such as CuI/L-proline catalyst have also been
reported for preparation of 1H-benzimidazoles and 1,3-dihydrobenzimidazol-2-ones
24]. Metal salt (FeCl ) with sulfur has been used as an iron–sulfur system for the
[
3
reaction between o-nitroanilines and alcohols to obtain benzimidazoles [25], while
the elemental sulfur system has been applied to obtain benzimidazole from aliphatic
amines and o-amino/mercaptan/hydroxyanilines without any catalyst [26], as well
as the CoBr /FeCl system to obtain 2-aryl benzimidazoles [27]. Metal-free KOH/
2
3
dimethyl sulfoxide (DMSO) has been reported as catalyst for synthesis of
benzimidazoles [28]. p-Toluenesulfonic acid was applied as Brønsted acid catalyst
for convenient synthesis of benzimidazoles [29]. Subsequently, various reagents
such as Yb(OTf) [30], Sc(OTf) [31], Bi(OTf) [32], and ionic liquids [33] have
3
3
3
been considered as catalysts for synthesis of benzimidazoles. However, the main
difficulty with such homogeneous catalysts is the difficult retrieval from the reaction
mixture. The product is separated from the reaction medium either by extraction
and/or precipitation by using other organic solvents [34].
1
23

Iron(III)–salen complex on a polymer scaffold as…
In modern synthetic organic chemistry, development of reusable protocols is one
of the most essential topics. Over more than two decades, a variety of solid-
supported metal catalysts have been developed by immobilizing metal on various
supports, representing an environmentally friendly approach. In contrast to
homogeneous catalysis, heterogeneous catalysts can be simply separated from the
reaction mixture [35, 36]. Applications of polymer-supported reagents in organic
synthesis have grown over the years due to their convenient handling, reusability,
and easy workup procedures. Moreover, polymers have been preferred to
immobilize metal complexes due to their functionalization, good accessibility,
better control over the catalytic activity, and excellent thermal stability. It is well
known that hydrophilic catalysts suffer deactivation by water due to capillary
condensation and slow water desorption. However, this problem can be avoided by
use of a hydrophobic catalyst [37]. Additionally, there are many reports involving
application of hydrophobic styrene-divinylbenzene copolymer in reactions includ-
ing water as byproduct [38, 39]. In coordination chemistry, salen
[
N,Nethylenebis(salicylimine)], a tetradentate symmetric ligand system, plays a
vital role as an advantageous chelating ligand due to its high stability under a variety
of reaction conditions and the ease of preparation with different substituents.
Transition metal–salen complexes have been effectively used in a wide range of
heterogeneous catalytic reactions [40, 41]. Representing an advantage over
homogeneous catalysts, such heterogeneous catalysts have been reported for
synthesis of benzimidazoles. Materials such as copper(II) oxide nanoparticles [42]
2
?
and Zn -K10-clay (clayzic) have been reported as heterogeneous solid acid
catalysts for synthesis of benzimidazoles [43]. However, polymer scaffold–Fe–salen
complex (PS–Fe–salen) complexes have not been reported for synthesis of
benzimidazoles. In continuation of our efforts towards development of efficient
methods for synthesis of heterogeneous catalysts for use in organic transformations
[44, 45], we report herein synthesis and characterization of a polymer scaffold–Fe–
salen (PS–Fe–salen) complex and its application as heterogeneous catalyst for
synthesis of benzimidazoles via reaction of o-phenylenediamine and benzaldehyde.
Experimental
Materials
All chemicals were procured at reagent or analytical grade with the maximum purity
available. 4-Vinylbenzyl chloride (used by washing with dil. NaOH), DMSO-d6,
and CDCl were obtained from Sigma Aldrich (India). FeCl , ethylenediamine, o-
3
3
phenyldiamine, benzaldehydes, and azobisisobutyronitrile (AIBN) were obtained
from SDFCL and Avra Synthesis Pvt. Ltd. Ethanol was purchased from Changshu
Yangyuan Chemical China. Acetonitrile, chloroform, tetrahydrofuran (THF),
and benzimidazole were acquired from Spectrochem Pvt. Ltd. and used directly
as received unless otherwise stated.
123

K. R. Balinge et al.
Characterization techniques
Nuclear magnetic resonance (NMR) spectra were acquired using a Bruker 400 MHz
instrument with tetramethylsilane (TMS) as internal standard in DMSO-d and
6
CDCl . FT-IR spectra were recorded using a Shimadzu spectrometer from KBr
3
pellets. Thermogravimetric analysis was carried out using a thermal gravimetric
analysis instrument (TG/DTA thermoanalyser SII, 7200, Seiko, Japan) under
-
1
nitrogen atmosphere at heating rate of 10 °C min in the temperature range of
3
ature of 77 K in liquid N using a Quantachrome Nova 1000 analyzer. Specific
0–800 °C. Brunauer–Emmett–Teller (BET) surface area was measured at temper-
2
surface area, average pore diameter, and pore volume were measured using
N adsorption–desorption isotherms. The surface morphology and elemental
2
composition of the complex were assessed by scanning electron microscopy (Carl
Zeiss EVO/18SH, UK) equipped with energy-dispersive X-ray (EDX) facility.
Synthesis of polymer scaffold–Fe–salen (PS–Fe–salen) complex
The polymer scaffold–salen ligand was prepared based on our previous report;
details regarding synthesis and characterization are provided in the Electronic
Supporting Information [46]. Synthesis of PS–Fe–salen complex was performed
with slight modification from literature [47]. FeCl (0.162 g, 1 mmol) in 10 mL
3
methanol was added to a suspension of PS–salen ligand (0.893 g, 1 mmol) in 20 mL
methanol. The reaction mixture was stirred for 2 h at 60 °C, then cooled, and the
solid was separated by filtration followed by washing with methanol, then dried in a
hot-air oven to obtain dark-brown PS–Fe–salen complex (Fig. 1) with yield of
7
4 %.
General procedure for one-pot synthesis of benzimidazoles
In a typical experiment, 30 mg PS–Fe–salen was added to a mixture of o-
phenylenediamine (1 mmol, 0.108 g) and benzaldehyde (1 mmol, 0.106 g)
in 10 mL ethanol. The reaction mixture was allowed to reflux for 24 h. The
heterogeneous catalyst was isolated by simple filtration and washed twice with
methanol and used for the next cycle; the product was recovered by simple
extraction of the reaction mixture with chloroform (10 mL 9 3). The isolated
combined layer was washed with water and dried over Na SO . Solvent was
2
4
removed under reduced pressure on a rotatory evaporator and purified to obtain
corresponding benzimidazoles. The obtained reaction products were confirmed
1 13
by H and C NMR (Electronic Supporting Information).
1
2
-Phenyl-1H-benzo[d]imidazole (2a) Yield (90 %); H NMR (400 MHz, DMSOd )
6
3
1
d = 12.92 (s, 1H), 8.19 (d, J = 8.30 Hz, 2H), 7.68 (m, 5H), 7.24 (m, 2H).
C
NMR (100 MHz, DMSOd ) d = 151.6, 144.2, 135.4, 130.6, 130.3, 129.4, 126.8,
6
1
23, 122.1, 119.3, 111.7.
1
23

Iron(III)–salen complex on a polymer scaffold as…
Fig. 1 Synthesis of polymer scaffold–Fe–salen (PS–Fe–salen) complex 1f
1
2
-(p-Tolyl)-1H-benzo[d]imidazole (2b) Yield (80 %);
H NMR (400 MHz,
DMSOd ) d = 12.89 (s, 1H), 8.20 (m, 2H), 7.62 (m, 4H), 7.22 (m, 2H), 2.49 (s,
6
1
3
3
H). C NMR (100 MHz, DMSOd ) d = 152.6, 152.9, 130.5, 128.4, 126.9, 122.6,
6
1
15.8, 21.5.
1
2
-(4-Methoxyphenyl)-1H-benzo[d]imidazole (2c) Yield (84 %);
H
NMR
(
400 MHz, DMSOd ) d = 8.16 (m, 2H), 7.67 (m, 2H), 7.40 (m, 2H), 7.22 (m,
6
13
2
1
H), 3.86 (s, 3H). C NMR (100 MHz, DMSOd ) d = 159.9, 151.9, 142.6, 136.1,
6
33, 122.7, 122.5, 119.1, 115.9, 55.6.
1
2
-(2-Methoxyphenyl)-1H-benzo[d]imidazole (2d) Yield (79 %);
H
NMR
(
400 MHz, DMSOd ) d = 8.15 (d, J = 7.2 Hz, 1H), 7.57 (dd, J = 3.2, 5.6 Hz,
6
2
H), 7.40 (t, J = 8.0 Hz, 1H), 7.15 (m, 3H), 7.04 (t, J = 7.2 Hz, 1H), 3.90 (s, 3H).
C NMR (100 MHz, DMSOd ) d = 157.4, 149.6, 138.6, 132.4, 130.2, 123, 121.7,
18.0, 115.6, 112.7, 56.4.
1
3
6
1
1
2
-(3,4,5-Trimethoxyphenyl)-1H-benzo[d]imidazole (2e) Yield (85 %); H NMR
(
400 MHz, DMSOd ) d = 7.85 (m, 2H), 7.65 (s, 2H), 7.43 (m, 2H), 4.0 (s, 6H)
6
13
3
.89 (s, 3H). C NMR (100 MHz, DMSOd ) d = 159.9, 151.9, 142.5, 139.1, 124.7,
6
1
23.5, 115.9, 55.6.
1
4
-(1H-Benzo[d]imidazol-2-yl)-N,N-dimethylaniline (2f) Yield (86 %); H NMR
(
400 MHz, DMSOd ) d = 8.8 (m, 2H), 8.2 (m, 2H), 8.0 (d, J = 8.9 Hz, 2H) 7.5
6
123

K. R. Balinge et al.
(
d, J = 5.4 Hz, 1H) 6.8 (d, J = 8.9, 2H), 3.0 (s, 6 H) 13C NMR (100 MHz,
DMSOd ) d = 151.6, 140.7, 128.2, 116.7, 54.8, 45.5.
6
1
5
-(1H-Benzo[d]imidazol-2-yl)-2-methoxyphenol (2g) Yield (70 %);
H NMR
(
400 MHz, DMSOd ) d = 7.7 (m, 2H), 7.40 (m, 2H), 7.2 (m, 2H), 6.9 (s, 1H),
6
1
3
3
.8 (S, 1H). C NMR (100 MHz, DMSOd ) d = 159.9, 151.9, 142.6, 136.1, 133,
6
1
22.7, 122.5, 119.1, 115.9, 55.6.
1
4
-(1H-Benzo[d]imidazol-2-yl)phenol (2h) Yield (84 %); H NMR (400 MHz,
1
3
DMSOd )) d = 7.7 (d, 2H), 7.15 (m, 4H), 6.9 (d, 1H). C NMR (100 MHz,
6
DMSOd ) d = 159.1, 151.1, 142, 134.4, 128.1, 123.2, 116.
6
1
2
-(4-Nitrophenyl)-1H-benzo[d]imidazole (2i) Yield (89 %); H NMR (400 MHz,
1
3
DMSOd ) d = 8.0 (m, 2H), 7.1 (m, 2H), 6.7 (m, 4H), C NMR (100 MHz,
6
DMSOd ) d = 151, 149.5, 148.3, 135.3, 127.8, 124.8, 117.7, 115.
6
1
4
-(1H-Benzo[d]imidazol-2-yl)benzonitrile (2j) Yield (73 %); H NMR (400 MHz,
DMSOd ) d = 13.17 (s, 1H), 8.3 (d, 2H), 8.0 (d, 2H), 7.7 (m, 1H), 7.5 (m, 1H), 7.3
6
1
3
(
m, 2H). C NMR (100 MHz, DMSOd ) d = 149.7, 144.2, 135.4, 134.4, 127.4,
6
1
23.9, 122.7, 119.8, 119.1, 112.1, 39.5.
1
2
-(4-Bromophenyl)-1H-benzo[d]imidazole (2k) Yield (71 %); H NMR (400 MHz,
1
3
DMSOd ) d = 13.01 (s, 1H), 8.1 (d, 2H), 7.7 (d, 2H), 7.6 (d, 2H), 7.2 (2H, m).
C
6
NMR (100 MHz, DMSOd ) d = 150.1, 143.9, 134.3, 129.3, 123.2, 122.2, 115.
6
1
2
-(4-Chlorophenyl)-1H-benzo[d]imidazole (2l) Yield (63 %); H NMR (400 MHz,
1
3
DMSOd ) d = 13.0 (s, 1H), 8.1 (d, 2H), 7.8 (m, 2H), 7.6 (2H, d), 7.2 (m, 2H).
C
6
NMR (100 MHz, DMSOd ) d = 150.2, 143.6, 134.6, 129.8, 128.9, 122.6, 118.5.
6
1
2
-(Furan-2-yl)-1H-benzo[d]imidazole (2m) Yield (74 %); H NMR (400 MHz,
DMSOd ) d = 13.9 (s, 1H)7.95 (m, 1H), 7.5 (s, 2H), 7.2 (m, 3H), 6.7 (m, 1H).
6
1
3
C NMR (100 MHz, DMSOd ) d = 145.5, 144.6, 143.5, 134.3, 122.3, 121.6,
6
1
18.7, 112.3, 111.4, 110.5.
Results and discussion
Catalyst characterization
The FT-IR spectra of the ligand and metal complex were compared to confirm the
coordination site that may be involved in the formation of the PS–Fe–salen complex
from the PS–salen ligand (Fig. 2I). The FT-IR spectrum of 1f showed the
-
1
disappearance of the peak at 3358 cm (–OH) compared with 1e, confirming
participation of OH group in the creation of Fe–O bond. Additional, it was found
-
1
that the band of PS–salen ligand 1e at 1631 cm
(C=N) shifted slightly
-
1
to 1616 cm , confirming effective participation of azomethine nitrogen in forma-
tion of the metal coordinate bond. These results confirm the formation of the PS–
Fe–salen complex.
1
23

Iron(III)–salen complex on a polymer scaffold as…
100
80
60
40
20
0
1
616
3
358
1
631
PS-Fe-slen
PS-salen
PS-Fe-salne (1f)
PS-salne (1e)
0
100 200 300 400 500 600 700 800
Temperature (°C)
4
000 3500 3000 2500 2000 1500 1000 500
-1
Wavenumber (cm
)
0
.0035
.0030
4
.0
.5
.0
.5
.0
.5
.0
.5
.0
0
3
3
2
2
1
1
0
0
0.0025
0.0020
0.0015
0.0010
0.0005
0.0000
0
.0
0.2
0.4
0.6
0.8
1.0
0
5
10 15 20 25 30 35
Pore Diameter (nm)
Relative Presure P/P
o
V
Fig. 2 I FT-IR spectrum of PS–salen ligand 1e and PS–Fe–salen complex 1f, II thermogravimetric
analysis (TGA) thermogram of PS–salen (1e) and PS–Fe–salen (1f), III BET isotherm, IV pore diameter
and pore volume of PS–Fe–salen, V SEM/EDX results of polymer scaffold–salen ligand 1e (A, B) and
polymer scaffold–Fe–salen complex 1f (C, D)
Thermogravimetric analysis (TGA) of the PS–salen ligand (1e) and PS–Fe–salen
-
1
complex (1f) was performed at heating rate of 10 °C min in N atmosphere over
2
the temperature range of 30–800 °C (Fig. 2II). The results showed initial weight
123

K. R. Balinge et al.
loss from both the PS–salen ligand and PS–Fe–salen complex below 110 °C of
around 8 %, which may be due to loss of physically adsorbed moisture. The weight
loss behavior of the salen ligand (1e, 45 %) and salen metal complex (1f, 32 %) at
the second decomposition temperature was substantially different, indicating that
the PS–Fe–salen complex was more stable than the PS–salen ligand. These data
reveal that the complex was stable and suitable for higher-temperature reaction.
Furthermore, the weight loss observed from both the ligand and metal complex may
be due to the polymer-scaffold benzimidazole group. These data confirm that the
PS–Fe–salen complex was thermally stable.
The surface area and pore size distribution of the PS–Fe–salen complex were
confirmed by BET surface area analysis of the adsorption/desorption isotherm. The
2
specific area of the PS–Fe–salen complex was found to be 3.856 m /g (Fig. 2III).
The total volume and average pore diameter of PS–Fe–salen were found to be
0
.007 cc/g and 1.560 nm, respectively (Fig. 2IV).
Scanning electron microscopy (SEM) images of the PS–salen ligand (Fig. 2V, A)
and PS–Fe–salen (Fig. 2V, C) indicated a change in surface morphology due to the
formation of the complex. Moreover, energy-dispersive X-ray spectroscopy (EDX)
analysis for the PS–salen ligand (Fig. 2V, B) and PS–Fe–salen complex (Fig. 2V,
B) revealed presence of Fe in the PS–Fe–salen complex. The SEM/EDX data
confirm successful formation of the metal complex (PS–Fe–salen).
Catalytic activity of polymer scaffold–Fe–salen complex
The parameters affecting the synthesis of benzimidazoles from benzaldehyde and o-
phenyldiamine are: the nature of the catalyst, the solvent, the catalyst loading, the
Table 1 Effect of solvents on synthesis of benzimidazole
a
Entry
Solvent
Temperature (°C)
Yield (%)
1
2
3
4
5
6
7
8
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
100
91
89
83
70
65
86
80
71
MeOH
2
H O
2
EtOH:H O
MeOH:H
DMSO
DMF
2
O
100
Toluene
Reflux
Reaction condition: o-phenyldiamine = (2 mmol, 216 mg), benzaldehyde (2 mmol, 212 mg),
cat = 60 mg, 24 h
a
Isolated yield
1
23

Iron(III)–salen complex on a polymer scaffold as…
temperature, the duration, and the substrate used. To initiate this study, we
confirmed the effect of different solvents on the synthesis of benzimidazoles.
Solvents such as EtOH, MeOH, H O, DMSO, tetrahydrofuran (THF), and toluene
2
(
Table 1, entries 1–3, 6–8) and cosolvents EtOH:H O and MeOH:H O (Table 1,
2 2
entries 4, 5) revealed comparable effect on the reaction. The best solvent was
selected as EtOH, showing the maximum product yield of 91 %. With the best
solvent in hand, we started optimization of the catalyst loading, temperature, and
time (Table 2). Initially, the model reaction was carried out in absence of catalyst,
giving product yield of around 20 % (Table 2, entry 1). FeCl and the ligand, i.e.,
3
PS–salen, showed isolated yield of 30 and 32 % (Table 2, entries 2 and 3). To
confirm the effect of the catalyst loading on the product conversion, we tried the
reaction, varying the amount of catalyst in the range of 10–40 mg (Table 2, entries 4
Table 2 Effect of amount of catalyst, temperature, and time on synthesis of benzimidazole
a
Entry
Catalyst
–
Catalyst amount (mg)
Temperature
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
30
30
30
10
20
25
30
40
25
25
25
25
25
25
25
25
25
25
25
70
70
70
70
70
70
70
70
RT
40
50
60
70
80
70
70
70
70
70
24
24
24
24
24
24
24
24
24
24
24
24
24
24
4
20
30
32
62
89
90
90
88
50
61
73
88
90
90
40
51
72
90
88
FeCl
b
3
1e
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1f
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
8
16
20
24
Reaction conditions: o-phenyldiamine = (1 mmol, 108 mg), benzaldehyde (1 mmol, 106 mg)
a
Isolated yield
b
PS–salen ligand
123

K. R. Balinge et al.
Table 3 Synthesis of 2-arylbenzimidazoles
a
Entry
Ar
Product
Yield (%)
1
2
3
4
5
6
7
8
9
Ph
2a
2b
2c
2d
2e
2f
90
80
84
79
85
86
70
84
89
73
71
63
74
4-MeC
6
H
4
4-MeOC
6
H
4
2-OMe-C
6 4
H
3,4,5-MeOC
(Me) N-C
3-OH,4-OMeC
4-OHC
4-NO
4-CNC
4-BrC
4-ClC
6 2
H
2
6 4
H
6
H
3
2g
2h
2i
6 4
H
2 6 4
C H
1
1
1
1
a
0
1
2
3
6
H
4
2j
6
H
4
2k
2l
6 4
H
C
4
H
3
O
2m
Isolated yield
and 8). The optimum amount of catalyst was found to be 25 mg, giving the highest
yield of the desired product of 90 % (Table 2, entry 6). With the optimum solvent
and catalyst amount in hand, we studied the effect of temperature on the reaction.
Increasing the reaction temperature from room temperature to 80 °C (Table 2,
entries 9–14), the optimum temperature was found to be 70 °C (Table 2, entry 13),
while further increase in the temperature to 80 °C showed no effect on the yield
(
Table 2, entry 14). Furthermore, we confirmed the effect of the reaction duration
on the product yield (Table 2, entries 15 and 19). The results indicated that 20 h was
the optimum time to achieve the highest yield (Table 2, entry 18). Moreover, there
was a slight decline in the product yield as the reaction duration was increased
further (Table 2, entry 19). Finally, the results showed that the optimized reaction
conditions were ethanol as reaction solvent, 25 mg of catalyst, temperature of
7
0 °C, and duration of 20 h.
With the optimum reaction condition in hand, we carried out the reaction
between o-phenyldiamine and several substituted benzaldehydes with electron-
donating and electron-withdrawing group (Table 3). Good to excellent yield of the
desired products was obtained with both electron-rich and electron-deficient
benzaldehydes (Table 3, entries 1–13). Aldehyde substrates bearing electron-
donating substituent on the benzaldehyde showed good to excellent product yield
(
70–90 %) (Table 3, entries 1–8). Meanwhile, OMe para-substituent on
1
23

Iron(III)–salen complex on a polymer scaffold as…
Fig. 3 Plausible mechanism for synthesis of 2-phenylbenzimidazole catalyzed by PS–Fe–salen
benzaldehyde showed slightly higher conversion compared with the ortho-
substituent (Table 3, entries 3, 4). This may be due to the steric effect of the
ortho-position, while the electron-donating nature of OH at para showed moderate
yield of the desired product (Table 3, entry 8), compared with 3-OH,4-OMe-
benzaldehyde (Table 3, entry 7). Furthermore, presence of strong electron-
withdrawing substituent on benzaldehyde (4-NO ) resulted in excellent product
2
yield (Table 3, entry 9), compared with (CN) on benzaldehyde (Table 3, entry 10).
However, attempts with halide-substituted benzaldehyde (Br, Cl) confirmed that the
bromine substituent was advantageous over chlorine to form the benzimidazole
(
Table 3, entries 11, 12). Even heterocyclic aldehyde (furfural) produced the
corresponding cyclized product without any difficulty (Table 3, entry 13). These
results clearly confirm that electron-donating as well as electron-windrowing
substituents on the benzaldehyde affected the product yield more or less in the
reaction with o-phenyldiamine.
A plausible mechanism for the construction of 2-substituted benzimidazoles (7)
under the optimized reaction conditions is shown in Fig. 3. Herein, PS–Fe–salen
123

K. R. Balinge et al.
acts as Lewis acid as well as oxidative agent. It is assumed that the reaction
proceeds via activation of aldehyde (2) by PS–Fe–salen followed by condensation
reaction with o-phenylenediamine (3), which is important for formation of the imine
derivative (5) stabilized by the PS–Fe–salen complex. The resulting imine finally
undergoes ring closure by intramolecular attack of the second amino group on C=N
double bond (5) to obtain hydrobenzimidazole (6) that subsequently undergoes
aromatization by oxidation to afford the desired product 2-substituted benzimida-
zole (7). This proposed mechanism is supported by the control experiment under
nitrogen atmosphere, which led to trace of product [48].
Stability and recyclability
As a benefit of heterogeneous catalysts is the ability to recycle them for the next run,
a model reaction was performed under the optimum reaction conditions. At the end
of the reaction, the catalyst was separated by simple filtration, washed with
methanol, and dried in a hot-air oven. The recovered PS–Fe–salen complex was
compared with fresh PS–Fe–salen catalyst (Fig. 4). From the FT-IR spectra, it was
concluded that the catalyst was stable with no alteration of the structure of the
complex during the course of the reaction. The catalyst was successively utilized in
up to five successive runs with appreciable product conversion (Fig. 5). Further-
more, the slight decline in the activity of the catalyst with each recycle may be due
to loss of catalyst during the workup procedure. To confirm the heterogeneous
nature of the catalyst, we performed a hot filtration test for the catalyst with the
optimum reaction conditions. In this test, the reaction was carried out at the
optimum conditions for 2 h, then the catalyst was filtered off from the reaction
mixture by filtration, and the reaction continued using the filtrate under the same
conditions. After removing the catalyst from the reaction mixture, it was found that
(
b)
(
a)
PS-Fe-salen recycle (b)
PS-Fe-salen fresh (a)
4
000 3500 3000 2500 2000 1500 1000 500
-
1
Wavenumber
Fig. 4 FT-IR spectra of PS–Fe–salen before and after reaction
1
23

Iron(III)–salen complex on a polymer scaffold as…
89
8
9
8
4
8
2
7
9
8
6
4
2
0
0
0
0
0
1
2
3
4
5
Runs
Fig. 5 Recyclability of PS–Fe–salen catalyst up to fifth run
there was no acceptable progress in the yield, verifying that the catalyst was
heterogeneous.
Conclusions
We synthesized and characterized a novel polymer scaffold–Fe–salen (PS–Fe–
salen) catalyst and used it for synthesis of benzimidazoles in good to excellent yield.
The catalyst was characterized by NMR, SEM/EDX, and FT-IR, and its thermal
stability confirmed by TGA analysis, demonstrating its applicability for high-
temperature reactions. The true heterogeneous nature of the PS–Fe–salen catalyst
was confirmed by hot filtration test, and it was recycled up to five cycles.
Comparison of the FT-IR spectra of fresh and recycled catalyst confirmed that the
functionality of the complex remained intact after the catalytic reaction. The main
advantages of the protocol are the highest yield of 2-phenyl-1H-benzo[d]imidazole
obtained with low catalyst loading, easy workup, and mild reaction conditions.
Further study on use of this catalyst in organic syntheses is ongoing in our
laboratory.
Acknowledgements The authors thank VIT-Vellore for providing ‘‘VIT SEED GRANT’’ for carrying out
this research work and SIF DST-VIT-FIST for NMR, GC-MS, FT-IR, and SEM/EDX, as well as VIT-
Vellore for providing necessary facilities to bring this article to this level. We are also grateful to the
Dean, School of Advanced Sciences, and all the scholars of our research laboratory ‘‘Smart Materials
Laboratory for Bio-sensing and Catalysis’’ VIT-Vellore, who encouraged the authors during this period.
123

K. R. Balinge et al.
References
1
. C. Kus, N. Altanlar, Turk. J. Chem. 27, 35 (2003)
. H.A. Barker, R.D. Smyth, H. Weissbach, J.I. Toohey, J.N. Ladd, B.E. Volcani, J. Biol. Chem. 235,
80 (1960)
2
4
3. R. Zou, K.R. Ayres, J.C. Drach, L.B. Townsend, J. Med. Chem. 39, 3477 (1996)
4. Y. Lu, J. Chen, J. Wang, C. Li, S. Ahn, C.M. Barrett, J.T. Dalton, W. Li, D.D. Miller, J. Med. Chem.
57, 7355 (2014)
5
6
7
8
9
. P.N. Presston, Chem. Rev. 74, 279 (1974)
. J.-X. Li, Z.-B. Qin, Y.-H. Li, G.-H. Cui, Ultrason. Sonochem. 48, 127 (2018)
. J.W. Cui, S.X. Hou, Y.H. Li, G.H. Cui, Dalton Trans. 46, 16911 (2017)
. J.M. Roque, T. Pandiyan, J. Cruz, E. Garcia-Ochoa, Corros. Sci. 50, 614 (2008)
. N. Singh, D.O. Jang, Org. Lett. 9, 1991 (2007)
10. J. Shao, Y. Qiao, H. Lin, H. Lin, J. Fluoresc. 19, 183 (2009)
11. A.J. Blacker, M.M. Farah, M.I. Hall, S.P. Marsden, O. Saidi, J.M.J. Williams, Org. Lett. 11, 2039
(2009)
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
2. K. Bahrami, M.M. Khodaei, F. Naali, J. Org. Chem. 73, 6835 (2008)
3. J.P. Lin, F.H. Zhang, Y.Q. Long, Org. Lett. 16, 2822 (2014)
4. S.K. Alla, R.K. Kumar, P. Sadhu, T. Punniyamurthy, Org. Lett. 15, 1334 (2013)
5. L.H. Du, Y.G. Wang, Synthesis 5, 675 (2007)
6. S. Hati, P. Kumar Dutta, S. Dutta, P. Munshi, S. Sen, Org. Lett. 18, 3090 (2016)
7. D. Xue, Y. Long, J. Org. Chem. 79, 4727 (2014)
8. X. Lv, W. Bao, J. Org. Chem. 74, 5618 (2009)
9. Y. Kim, M.R. Kumar, N. Park, Y. Heo, S. Lee, J. Org. Chem. 76, 9577 (2011)
0. D. Mahesh, P. Sadhu, T. Punniyamurthy, J. Org. Chem. 80, 1644 (2015)
1. J. Peng, M. Ye, C. Zong, F. Hu, L. Feng, X. Wang, Y. Wang, C. Chen, J. Org. Chem. 76, 716 (2011)
2. D. Mahesh, P. Sadhu, T. Punniyamurthy, J. Org. Chem. 81, 3227 (2016)
3. M.M. Guru, A. Ali, T. Punniyamurthy, J. Org. Chem. 76, 5295 (2011)
4. X. Diao, Y. Wang, Y. Jiang, D. Ma, J. Org. Chem. 74, 7974 (2009)
5. T.B. Nguyen, L. Ermolenko, A. Al-Mourabit, Synthesis 47, 1741 (2015)
6. T.B. Nguyen, L. Ermolenko, W.A. Dean, A. Al-mourabit, Org. Lett. 14, 5948 (2012)
7. T.B. Nguyen, J. Le Bescont, L. Ermolenko, A. Al-Mourabit, Org. Lett. 15, 6218 (2013)
8. H. Baars, A. Beyer, S.V. Kohlhepp, C. Bolm, Org. Lett. 16, 536 (2014)
9. M.S. Mayo, X. Yu, X. Zhou, X. Feng, Y. Yamamoto, M. Bao, Org. Lett. 16, 764 (2014)
0. L. Wang, J. Sheng, H. Tian, Synth. Commun. 34, 4265 (2004)
1. L. Fan, L. Kong, W. Chen, Heterocycles 91, 2306 (2015)
2. J.S. Yadav, B.V.S. Reddy, K. Premalatha, M.S.R. Murty, J. Mol. Catal. A Chem. 271, 161 (2007)
3. H.G.O. Alvim, H.C.B. Oliveira, G. Bataglion, M.N. Eberlin, L.M. Ramos, W. Silva, RSC Adv. 5,
69418 (2015)
3
3
3
3
3
3
4
4
4
4
4
4
4
4. A.G. Khiratkar, N. Muskawar, P.R. Bhagat, RSC Adv. 6, 105087 (2016)
5. A. Kasprzak, M. Bystrzejewski, M. Poplawska, Dalton Trans. 47, 6314 (2018)
6. L.Z. Fekri, R. Maleki, J. Heterocycl. Chem. 54, 1167 (2016)
7. B. Wang, W. Ran, W. Sun, K. Wang, Ind. Eng. Chem. Res. 51, 3932 (2012)
8. J. Xie, Q. Zhang, K.T. Chuang, Catal. Lett. 93, 181 (2004)
9. J. Xie, Q. Zhang, K.T. Chuang, Appl. Catal. A 220, 215 (2001)
0. N.T.S. Phan, D.H. Brown, P. Styring, Tetrahedron Lett. 45, 7915 (2004)
1. F. Siga, H. Temel, M. Aydemir, Y. Selim, S. Pasa, A. Baysal, Appl. Catal. A Gen. 449, 172 (2012)
2. P. Saha, T. Ramana, N. Purkait, M.A. Ali, R. Paul, T. Punniyamurthy, J. Org. Chem. 74, 8719 (2009)
3. A. Dhakshinamoorthy, K. Kanagaraj, K. Pitchumani, Tetrahedron Lett. 52, 69 (2011)
4. K.R. Balinge, A.G. Khiratkar, P.R. Bhagat, J. Mol. Liq. 242, 1085 (2017)
5. K.R. Balinge, A.G. Khiratkar, P.R. Bhagat, J. Organomet. Chem. 854, 131 (2018)
6. K.R. Balinge, A.G. Khiratkar, P.N. Muskawar, K. Thenmozhi, P.R. Bhagat, Res. Chem. Intermed.
44, 2075 (2018)
4
7. S. Gazi, R. Ananthakrishnan, N.D.P. Singh, J. Hazard. Mater. 183, 894 (2015)
8. G. Brahmachari, S. Laskarm, P. Barik, RSC Adv. 3, 14245 (2013)
4
1
23