Eco-friendly highly efficient solvent free synthesis of benzimidazole derivatives over sulfonic acid functionalized graphene oxide in ambient condition

Article abstract of DOI:10.1007/s11164-016-2745-y

Abstract: Sulfonated graphene oxide (GO-HSO₃) heterogeneous catalyst was prepared at molecular level and characterized by using various modern analytic and spectroscopic methods. Using prepared heterogeneous catalyst GO-HSO₃, benzimidazole synthesis was carried out by means of reacting diamine and aldehyde at room temperature in solvent free condition. The catalyst GO-HSO₃ showed tremendous catalytic activity in selective synthesis of benzimidazole, as a result 100?% conversion of reactants and up to 89.0?% yield of respective benzimidazole was achieved using 0.1?mg of catalyst in very short reaction duration. The GO-HSO₃ catalyst was separated from the reaction mixture by simple filtration process at the end of reaction and reused for six successive cycles without noteworthy loss of catalytic activity and selectivity. Key advantageous of this protocol is high yield, low cost, and easy work-up procedure as well as short reaction time and solvent free condition. The present method is found eco-friendly, highly efficient, solvent free, high yielding, and clean method for the synthesis benzimidazole derivatives at room temperature. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s11164-016-2745-y

Res Chem Intermed
DOI 10.1007/s11164-016-2745-y
Eco-friendly highly efficient solvent free synthesis
of benzimidazole derivatives over sulfonic acid
functionalized graphene oxide in ambient condition
Mantosh B. Swami1,2 Arvind H. Jadhav3
•
•
Sushil R. Mathpati4 Hanmant G. Ghuge1
•
•
Sudhakar G. Patil1
Received: 20 May 2016 / Accepted: 12 September 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Sulfonated graphene oxide (GO-HSO3) heterogeneous catalyst was prepared
at molecular level and characterized by using various modern analytic and spectroscopic
methods. Using prepared heterogeneous catalyst GO-HSO3, benzimidazole synthesis
was carried out by means of reacting diamine and aldehyde at room temperature in
solvent free condition. The catalyst GO-HSO3 showed tremendous catalytic activity in
selective synthesis of benzimidazole, as a result 100 % conversion of reactants and up to
89.0 % yield of respective benzimidazole was achieved using 0.1 mg of catalyst in very
short reaction duration. The GO-HSO3 catalyst was separated from the reaction mixture
by simple filtration process at the end of reaction and reused for six successive cycles
without noteworthy loss of catalytic activity and selectivity. Key advantageous of this
protocol is high yield, low cost, and easy work-up procedure as well as short reaction
time and solvent free condition. The present method is found eco-friendly, highly effi-
cient, solvent free, high yielding, and clean method for the synthesis benzimidazole
derivatives at room temperature.
Mantosh B. Swami and Arvind H. Jadhav have contributed equally to this work.
&
&
Arvind H. Jadhav
jadhav.ah@gmail.com
Sudhakar G. Patil
sg_patil123@rediffmail.com
1
2
3
Department of Chemistry, Maharashtra Udayagiri Mahavidyalaya, Udgir, Latur 413517, India
Department of Chemistry, Mahatma Basweshwar Mahavidyalay, Latur, Latur 413512, India
Department of Energy Science and Technology, Energy and Environment Fusion Technology
Center, Myongji University, Myongji-ro 116, Cheoin-gu, Yongin-si, Gyeonggi-do 449-728,
Republic of Korea
4
Department of Chemistry, Shri Madhavrao Patil Mahavidyalaya, Murum, Osmanabad 413605,
India
123

M. B. Swami et al.
Keywords Graphene oxide Á Heterogeneous catalyst Á Benzimidazole derivative
synthesis Á Solvent free reaction Á Sulfonation of graphene oxide
Introduction
Benzimidazole derivatives have acknowledged much attention in the field of
medicinal chemistry as well as used as essential intermediates for the synthesis of
wide pharmaceutical compounds [1–4]. Derivatives of benzimidazole have been
related with wide range of biological activities together with anti-cancer, anti-
glycation, anti-inflammatory, anti-urease, anti-fungals, anti-bacterial, anthelmintic,
proton pump inhibitors, anti-viral, anti-oxidants [5–14]. Furthermore, with their
biological consequence, benzimidazoles form unvarying complexes with diverse
metals in transition group [13–15]. Metal chelations of 2-substituted imidazole and
benzimidazole based structures with various ligands have been published with
mono, bi and tri dentate co-ordination structures [15]. As a result, the preparation
and synthesis of benzimidazoles have gained significant consideration in recent
years.
Several methods have been resulted for the synthesis of benzimidazole as well as
their derivatives. The condensation reaction of different organic functionalized
carboxylic acids with 1,2-phenylenediamines or their similar derivatives is a
common place technique but it needs harsh reaction conditions and high reaction
temperature like at in the range of 150–200 °C [16]. Another option came up with
the condensation of aldehyde with 1, 2 phenylene diamine in attendance of different
catalysts like Ceric ammonium nitrate, silica supported sulfuric acid, In(OTf)3,
iodine, SiO2/ZnCl2, PEG, silica supported sodium hydrogen sulphate, H2O2/
Fe(NO3)3 [17–24]. Benzimidazole derivatives have also been prepared from the
oxidative condensation of 1,2-arylenediamines with aldehydes using different
oxidative and catalytic reagents such as oxygen [25] 1,4-benzoquinone [26]
nitrobenzene (high boiling oxidant/solvent) [27] 2,3-dichloro-5, benzofuroxan [28].
In recent time, without solvent synthesis of benzimidazoles in presence of MW
irradiation using metal halide supported alumina, KSF clay, silica supported halides,
and solid Yb(OTf)3 as catalyst have also been reported [17–21]. However, many of
these approaches suffer from one or more drawbacks such as requirement of low
yields, strong acidic conditions, long reaction times, tedious workup procedures,
requirement of excess amounts of catalyst and use of toxic reagents, catalysts or
solvent. Therefore, much development has been made in the synthesis of
benzimidazoles but it is still motivating to develop green and simple routes, which
is of significance from a point of view of green chemistry and sustainable
development.
Solid acids have the great potential to replace liquid acids as eco-friendly benign
heterogeneous acid catalysts [29–32]. Acidic carbons and materials based on the
impression of green chemistry were investigated as constant and highly active
protonic solid acid catalysts for several acid catalyzed transformations [33].
Graphene and its derivatives (graphene oxide as well as reduced graphene oxide)
have attracted a great attention and have been widely used in the field of catalysis
123

Eco-friendly highly efficient solvent free synthesis of…
and engineering science [34]. Because of its physical as well as chemical properties
such as high surface area, and admirable mechanical properties, GO has come
forward as a capable support material for heterogeneous catalysis [33, 34]. In
particular, unlike other common catalyst supports, graphene has a two-dimensional
structure that allows reactive species on it to be readily accessed with limited mass-
transfer resistance [33]. Graphene oxide (GO) includes high density of hydrophilic
organic functional groups including hydroxyl, carboxyl, and epoxy functional
groups [34]. However, these hydrophilic organic functionality can be applied for
further alteration of GO and such kind of modified GO is a capable candidate as
heterogeneous acid catalyst for organic transformation as well as industrial
applications [33, 34]. Recently, it is confirmed that, the efficiency of GO as a solid
acid catalyst for organic transformation such as esterification of organic acids with
alcohols [35] and ring-opening of epoxides with various alcohols [36, 37]. In
addition, using modified GO as catalyst for cyclization between OPD and
substituted benzaldehyde to make industrially essential chemicals for other
constructive chemical reactions were also determined [33, 34]. To the best of our
knowledge, till date there is no report of synthesis of benzimidazole derivatives by
using covalently modified GO-HSO3 as heterogeneous catalyst at room temperature
in solvent free reaction.
In the present report, we describe the successful preparation and covalent
modification of GO into GO-HSO3 as heterogeneous catalyst for the one-pot
synthesis of benzimidazole derivatives in solvent free condition at room temper-
ature. Prepared heterogeneous GO-HSO3 catalyst was characterized by various
analytical and spectroscopic techniques such as FT-IR, EDX, XRD, FE-TEM, FE-
SEM, TGA, and N2 adsorption–desorption analysis. Obtained results from these
characterization methods reveal that, HSO3 functionality covalently bonded to the
graphene oxide surface. After successfully characterization of heterogeneous GO-
HSO3 catalyst, it was tested for synthesis of benzimidazole derivatives under
solvent free condition. As results catalyst showed 100 % conversion of reactant and
86.0 % yield of respective benzimidazole. In addition, present protocol needs just
filtration for the separation of catalyst from products, which shows unique green
method impression for this protocol among other reported liquid acid catalysts. The
separated catalyst after treatment can be recycled number of times (six cycles)
without losing acidic functionality as well activity in benzimidazole synthesis.
Experimental
Materials
For the synthesis of graphene oxide, graphite flake (natural, 325 mesh) with a purity
of 99.8 % was purchased from Alfa Aesar. NaNO3 (95.0 %) and KMnO4 (99.0 %)
were obtained from Sigma Aldrich (Germany). H2SO4 (95–98 %) and H2O2 (30 %)
were obtained from commercial sources. All crucial preliminary materials for
benzimidazole derivatives and necessary reagents were acquired from Sigma-
123

M. B. Swami et al.
Aldrich and used without additional distillation. All solvents were purified and dried
by typical methods earlier to use.
Catalyst preparation
To prepare the sulfonated graphene oxide (GO-SO3H) in this study, pure GO was
obtained by using reported method described in the literature [36]. After getting the
pure graphene oxide followed the sulfonation process described below in Scheme 1.
The heterogeneous GO-SO3H catalyst was obtained by the sulfonation reaction of
GO in chloroform with chlorosulfonic acid. In a representative process, in 50 ml of
chloroform, 1.0 g of GO was mixed properly and for 1.5 h sonicated at room
temperature. After sonication process, a black very well dispersed GO suspension
was obtained. After that, carefully addition of 0.5 g of chlorosulfonic acid was done
drop wise to the dispersed GO solution in a two necked round-bottomed flask. The
prepared solution was then instantly refluxed with magnetic stirrer. In addition the
round-bottomed flask equipped with a cold-water condenser and stirred the reaction
mixture for 4 h at 70 °C. It should be well-known that the catalyst GO-SO3H
preparation steps were performed in a vacuum hood and some careful protection
were taken during the addition of chlorosulfonic acid and its proper assimilation into
the GO suspension. After 4 h of sulfonation reaction, the resulting brown
suspension solution was cooled at room temperature naturally. Later on, filtered
and washed with excess ethanol and water to remove organic moieties on the
surface until the pH of the filtrate became neutral. The catalyst sample was then
dried at 110 °C for 12 h in a vacuum oven, and further this material was used for the
catalytic activity.
Catalyst characterization methods
XRD patterns (Powder X-ray diffraction) of the GO-SO3H catalyst and precursors
were recorded on Rigaku Miniflex X-ray diffractometer (Rigaku Corporation,
Japan) with a 4° min-1 scan speed and a scan range of 5–90° at 30 kV and 15 mA
˚
using Ni filtered Cu Ka radiation (k = 1.5406 A). Thermogravimetric analyses
Scheme 1 Schematic representation of preparation of sulfonated graphene oxide from initial source
graphite
123

Eco-friendly highly efficient solvent free synthesis of…
(TGA) were performed on Scinco TGA N-100 device with ramp rate of 10 °C/min
in nitrogen condition. FT-IR spectra of prepared catalysts were taken on a Varian
2000 IR spectrometer (Scimitar series) by using the KBr disc method. The
Brunauer–Emmett–Teller (BET) surface areas of the nanostructures were obtained
from N2 sorption isotherms, acquired using a BEL Japan (Belsorp-II) instrument.
The surface analysis as well as morphology of prepared catalysts was considered by
scanning electron microscopy (SEM) by using a Hitachi, S-3500 N SEM apparatus.
The illustrations for TEM analysis were prepared by dropping about 10 ll of
sonicated dilute solution of nanostructures in ethanol onto carbon-coated copper
grids and gradually drying at atmospheric condition. Energy dispersive X-ray
spectrometry (EDX) or elemental mappings were performed on SEM apparatus
united with an INCA instrument for EDS with scanning electron electrode at 20 kV.
The benzimidazole products were characterized by NMR spectra recorded on
Bruker VRMS-400 MHz NMR spectrometer using CDCl3 as a solvent. The
1
described chemical shifts were in contrast to TMS as reference for H and 13C
NMR. All obtained benzimidazole products have been formerly reported and all
known obtained products gave reasonable analytical data analogous to the reported
literature values.
General reaction procedure for synthesis of benzimidazole derivatives using
sulfonated graphene oxide catalyst
To a mixture of diamine (1 mmol) and aldehyde (1 mmol) was added in 50 ml
round bottom flask. A known catalytic amount of sulfonated graphene oxide was
also added in the reaction mixture. There is no any addition of solvent as well as co-
catalysts were done. Then, the obtained mixture was magnetically stirred under
open atmosphere at room temperature for appropriate time. After the completion of
the reaction (checked by TLC), ethyl acetate was added in the reaction mixture and
filter by using Whatman filter paper. Washed the catalyst by ethyl acetate thrice and
collect the washings and were combined and evaporated under vacuum on rotary
evaporator. The crude solid product, nevertheless pure enough on TLC (70:30 %),
was then passed through a short column of silica gel to afford pure benzimidazole
1
products and further characterized by H and 13C NMR spectroscopy.
2-Phenyl-1H-benzo[d]imidazole (Table 3, Entry 1)
1
Yield 88 %; H NMR (400 MHz, DMSO): d 12.91 (s, H), 7.26 (m, 2H), 7.46 (m,
H), 7.53 (m, 2H); 7.62 (m, 2H), 8.18 (m, 2H) ppm; 13C NMR (100 MHz, DMSO):
d: 115.6, 123.2, 127.6, 129.7, 131.2, 133.9, 142.1, 152.7 ppm.
6-Methyl-2-phenyl-1H-benzo[d]imidazole (Table 3, Entry 2)
Yield 74 %; 1H NMR (400 MHz, DMSO): d: 2.31 (s, 3H), 7.13 (d, H), 7.42 (m, H),
7.41 (s, H), 7.51 (m, 2H); 7.56 (d, H), 8.21 (m, 2H), 12.76 (s, H) ppm; 13C NMR
(100 MHz, DMSO): d: 21.6, 116.1, 116.4, 125.9, 127.7, 129.3, 130.9, 131.1, 132.8,
134.6, 135.8, 152.7 ppm.
123

M. B. Swami et al.
2-(p-Tolyl)-1H-benzo[d]imidazole (Table 3, Entry 3)
1
Yield 81 %; H NMR (400 MHz, DMSO): d: 2.34 (s, 3H), 7.24 (m, 2H), 7.26 (d,
2H), 7.58 (d, 2H); 8.54 (d, 2H), 12.86 (s, H) ppm; 13C NMR (100 MHz, DMSO): d:
21.3, 114.9, 122.8, 128.7, 129.4, 132.1, 141.7, 151.9 ppm.
6-Methyl-2-(p-tolyl)-1H-benzo[d]imidazole (Table 3, Entry 4)
Yield 69 %; 1H NMR (400 MHz, DMSO): d: 2.31 (s, 3H), 7.12 (d, H), 7.31 (d, 2H),
7.47 (d, 1H); 7.49 (d, 1H); 8.49 (d, 2H), 12.92 (s, H) ppm; 13C NMR (100 MHz,
DMSO): d: 20.98, 115.3, 124.96, 127.87, 129.00, 131.89, 132.17, 134.75,
152.61 ppm.
6-Methyl-2-(p-tolyl)-1H-benzo[d]imidazole (Table 3, Entry 5)
Yield 61 %; 1H NMR (400 MHz, DMSO): d: 2.36 (s, 3H), 3.87 (s, 3H), 6.93 (d, H),
7.17 (s, H); 7.26 (d, 2H); 7.91 (s, H), 8.59 (d, 2H), 12.82 (s, H) ppm; 13C NMR
(100 MHz, DMSO): d: 20.82, 54.9, 104.6, 112.7, 117.1, 128.6, 130.1, 131.9, 134.2,
156.3 ppm.
6-Methoxy-2-phenyl-1H-benzo[d]imidazole (Table 3, Entry 6)
Yield 78 %; 1H NMR (400 MHz, DMSO): d: 3.87 (s, 3H), 6.87 (d, H), 7.17 (s, H);
7.43 (m, H); 7.47 (d, H), 8.26 (m, 2H), 12.79 (s, H) ppm; 13C NMR (100 MHz,
DMSO): d: 55.7, 102.1, 111.1, 116.3, 127.3, 129.6, 134.2, 134.7, 139.3. 155.7 ppm.
6-Methoxy-2-(4-methoxyphenyl)-1H-benzo[d]imidazole (Table 3, Entry 7)
Yield 83 %; 1H NMR (400 MHz, DMSO): d: 3.91 (s, 3H), 3.96 (s, 3H) 6.91 (d, H),
7.07 (d, H), 7.12 (s, H); 7.46 (d, H); 7.92 (d, H), 12.91 (s, H) ppm; 13C NMR
(100 MHz, DMSO): d: 55.8, 103.2, 110.9, 113.6, 114.6, 116.3, 131.1, 134.3, 138.7,
156.1 ppm.
6-Chloro-2-phenyl-1H-benzo[d]imidazole (Table 3, Entry 8)
1
Yield 81 %; H NMR (400 MHz, DMSO): d: 7.16 (d, H), 7.43 (m, H), 7.51 (d, H)
7.56 (q, 2H), 8.26 (m, 2H); 8.34 (s, H), 12.82 (s, H) ppm; 13C NMR (100 MHz,
DMSO): d: 115.7, 116.3, 124.1, 127.3, 129.1, 129.7, 130.7, 131.3, 132.5, 134.6,
152.6 ppm.
6-Chloro-2-(4-chlorophenyl)-1H-benzo[d]imidazole (Table 3, Entry 9)
Yield 83 %; 1H NMR (400 MHz, DMSO): d: 7.06 (d, H), 7.32 (d, H), 7.47 (d, 2H),
8.17 (d, 2H); 8.39 (s, H), 12.91 (s, H) ppm; 13C NMR (100 MHz, DMSO): d: 115.7,
116.3, 124.6, 128.5, 129.4, 129.9, 131.2, 132.7, 132.9, 134.3, 153.1 ppm.
123

Eco-friendly highly efficient solvent free synthesis of…
2-Phenyl-1H-benzo[d]imidazole-6-carbaldehyde (Table 3, Entry 10)
Yield 78 %; 1H NMR (400 MHz, DMSO): d: 13.26 (s, H), 9.78 (S, H) 8.28 (m, 2H),
7.92 (s, H), 7.53 (d, H), 7.59 (t, 2H); 7.39 (m, H) ppm; 13C NMR (100 MHz,
DMSO): d: 115.2, 118.5, 125.1, 127.2, 129.7, 131.3, 131.7, 134.6, 139.3, 147.6,
152.4 ppm.
6-Nitro-2-phenyl-1H-benzo[d]imidazole (Table 3, Entry 11)
Yield 81 %; 1H NMR (400 MHz, DMSO): d: 12.11 (s, H), 7.39 (m, H), 7.56 (t, 2H),
7.69 (d, H), 7.93 (s, H); 8.13 (d, H), 8.29 (d, 2H) ppm; 13C NMR (100 MHz,
DMSO): d: 112.8, 116.1, 118.7, 127.6, 129.3, 131.1, 134.3, 139.7, 144.5, 147.9,
152.7 ppm.
Results and discussion
Catalyst characterization
FT-IR analysis of prepared materials
The reaction results of the chemical modification of GO are shown in Fig. 1. To
determine the complete modification of GO into GO-HSO3, comparative study of
pure GO and pure graphite were also performed by FTIR spectroscopy. In all
analyzed samples a wide signal situated at 3600–2800 cm-1 recognized due to the
stretching vibration of hydroxyl (–OH) groups present in the catalysts. In pure GO
Pure Graphite
Pure Graphene Oxide
C=0
C-0
C-0-C
C-0H
Sulfonated Graphene Oxide
0
500 1000 1500 2000 2500 3000 3500 4000
Wavelength (cm-1)
Fig. 1 FT-IR analysis of prepared sulfonated graphene oxide catalyst, graphene oxide and graphite
123

M. B. Swami et al.
before sulfonation signal at 1710–1705 cm-1 attributed due to the carboxylic
groups and strong signal at 1350 cm-1 is due to deformation of vibration in C–OH.
In addition a peak at 1040–1023 cm-1 represented by functional C–O groups and a
peak located at around 950 cm-1 from epoxy groups present in the pure GO. The
spectrum of pure GO indicates the presence of O–H stretching broad peak at
3430 cm-1, C=C stretching at 1590 cm-1, C–O stretching at 1050 cm-1, and C–
OH stretching at 1220 cm-1, respectively. These all representative peaks of FT-IR
analysis were showed that graphite is entirely oxidized into GO. In the IR spectrum
of GO-SO3H, including all these parent peaks which belongs to GO some other
peaks also observed belong to the HSO3 group. The presence of vibrational bands at
1040, 1080, and 1171 cm-1 (arising from O–S–O stretching) and at 1125, 1277, and
1320 cm-1 (from the SO3H stretching) in the FT-IR spectrum was showed clear
indication of the presence of SO3H in GO-SO3H [37]. The above-mentioned FT-IR
bands for O–S–O and SO3H stretching vibrations were observed throughout sample
and results indicates that, the SO3H group is strongly covalently bonded on the GO
surface.
XRD analysis of catalysts
The X-ray diffraction pattern (XRD) characterization results of pure graphite, pure
GO and sulfonated GO are shown in Fig. 2. For the pure graphite sample, the (002)
sharp peak appears at 27°, indicating an interlayer spacing of 0.34 nm. After
completion of oxidation process induced expansion of the (002) peak shifts to 11°,
theta value in pure GO which suggested that complete oxidation process occurred
and the interlayer space distance enlarged to 0.51 nm by the oxidation method.
These results are consistent with the data reported in the literature. After
modification of sulfonation process, the resulting graphene sulfonated GO nano-
sheets from pure GO showed similar parental peak pattern as GO but the intensity of
Sulfonated Graphene Oxide
Pure Graphene Oxide
Pure Graphite
(002)
(002)
(002)
0
10
20
30
40
50
60
70
80
2 theta (o)
Fig. 2 XRD analysis of sulfonated graphene oxide as well as graphene oxide and graphite
123

Eco-friendly highly efficient solvent free synthesis of…
15
Pure Graphite
10
5
0
Pure Graphene Oxide
30
20
10
0
Sulfonated Graphene Oxide Pure Graphene Oxide
6
4
2
0
0.0
0.5
1.0
Relative Pressure (P/P0)
Fig. 3 Adsorption–desorption isotherms of sulfonated graphene oxide as well as graphene oxide and
pure graphite
peaks is very weak and broad at approximately near at 25°. This may stem from the
change of the chemically covalently bonded the sulfonated group over the GO and
these kinds of results are reported previously [34–36]. In addition, the interlayer
spacing (d-spacing) value for GO was 0.51 nm, while the interlayer spacing of GO-
HSO3 was calculated to be 0.79 nm, which revealed the increase of distance
between GO-HSO3 nano-sheets by sulfonation [33, 34].
Adsorption/desorption isotherms and surface area analysis of prepared
heterogeneous catalysts
The adsorption/desorption isotherms and BET test results are shown in Fig. 3. The
corresponding specific surface area of pure graphite, pure graphene oxide and
sulfonated graphene oxide are 8.0, 89.0, and 73.0 m2/g, respectively. The increased
specific surface area in pure graphene oxide could be attributed due to exfoliation of
graphite into graphene oxide. This result reveals that complete modification of
graphite into graphene oxide occurred in the oxidation process [33–35]. However,
when the modification of pure graphene oxide into sulfonated graphene oxide
occurred, surface area of GO-HSO3 was reduced. Result showed that sulfonated
graphene oxide showed 73.00 m2/g surface areas. Reported literature showed that,
reduction in the surface area of GO-HSO3 due to the HSO3 acidic moiety
chemically grafted on the surface of graphene oxide [36]. However, obtained
surface area for GO-HSO3 is 73.00 m2/g r is highly efficient for any organic
transformation [34]. Hence from these results it is reveals that, successfully
modification of GO into the GO-HSO3 occurred.
123

M. B. Swami et al.
100
95
90
85
80
75
70
65
60
55
Phase -1
Phase-2
Phase-3
Pure Graphite
Graphene Oxide
Sulfonated Graphene Oxide
0
100
200
300
400
500
600
700
800
Temperature (oC
)
Fig. 4 TGA analysis of prepared sulfonated graphene oxide, pure graphene oxide and pure graphite
Thermogravimetric analysis of sulfonated graphene oxide
Figure 4 displays the TGA curves of pure graphite, pure graphene oxide and
sulfonated graphene oxide samples. As seen in the figure, graphite did show any
weight loss in the determined temperature phase of TGA analysis. In the TGA
analyses of pure GO, the overall weight loss of 27 % for GO occurs in three
successive steps. The primary step is a stable weight loss of 3–5 % recognized due
to the vaporization of physically adsorbed water molecules and take place at
approximately 100 °C [33]. Then a second speedy weight loss of 8–10 % observed
due to the breakdown of the oxygen-containing organic functional groups such as
COOH (carboxyl), OH (hydroxyl), C=O (carbonyl) and epoxy groups in the
temperature phase of 120–208 °C. Furthermore, third weight loss of 14–15 %
accredited due to successive breakdown of carbon skeleton in the temperature phase
range of 210–800 °C is observed and finally total residual weight of GO obtained at
800 °C was around 75 %. Later on there is no weight loss after this designated
temperature and finally sample approximately reserved constant weight throughout
the analysis. On the other side, in the sulfonated GO total weight loss observed
approximately 45 %, in which initially 6.0 % weight loss observed due to the
vaporization of absorbed moisture at 100–110 °C. There is successive rapid
decrease in the weight loss 8–12 % observed at 120–210 °C due to the
decomposition of unreacted oxygen functional groups. In the next step, the
20–25 % weight loss in the temperature range can be attributed to decomposition of
sulfonated groups which is. Later on again sudden decreases in weight loss was
observed due to the sulfonated group functionality at approximately at 400–550 °C,
which shows 20–25 % weight loss belong to the sulfonated functionality covalently
bonded on GO [33, 34]. These obtained results are quite similar with the previously
reported methods.
123

Eco-friendly highly efficient solvent free synthesis of…
a
b
c
d
5 nm
50 nm
Fig. 5 FE-SEM and TEM analysis of pure graphene oxide (a, c) and sulfonated graphene oxide (b,
d) respectively
FE-SEM and FE-TEM analysis of prepared heterogeneous catalyst
Scanning electron microscopy (SEM) and TEM analysis of prepared catalysts GO-
HSO3 and pure graphene oxide were performed for investigating the morphology
and effect of sulfonyl functionality groups on the obtained GO-HSO3. As shown in
Fig. 5, pure GO showed nano sheets like structure in SEM image (Fig. 5a) in
addition similarity structures consistent was also observed with TEM images of pure
GO (Fig. 5b). Modified GO-HSO3 reveals the sulfonation of GO led to further
exfoliation of the clusters of sheets into a random pile. Similar to the SEM images,
the TEM image of GO-HSO3 showed that the sheets were randomly oriented and
crumpled sheets (Fig. 5c, d). Obtained FE-SEM and TEM images reveals that,
successfully modification of GO into GO-HSO3 was occurred without damaging the
spinal nano structure of Graphene oxide.
Elemental analysis (EDX) of sulfonated graphene oxide
Quantitative energy dispersive X-ray spectroscopy (EDS) mapping of pure graphite,
pure GO and GO-HSO3 were performed to investigating the successful oxidation
and distribution of sulfonated functionality on the obtained modified GO–HSO3
(Fig. 6). In the pure graphite and pure GO, distributions of carbon and oxygen
elements were determined. Before the oxidation, pure graphite showed homogenous
distribution of 51 % of carbon and 47 % oxygen respectively. Whereas after
123

M. B. Swami et al.
Pure Graphite
Graphene Oxide
Catalyst
% of C
% of O
% of S
GO-HSO3
Wt. Atm. Wt. Atm. Wt. Atm.
%
%
%
%
%
%
Graphite 51.0 58.64 46.8 404
-
-
Graphene 43.4 50.6 56.5 49.4
Oxide
-
-
GO-HSO3 50.5 57.4 45.9 39.6 3.89 1.96
Fig. 6 Elemental analysis of prepared heterogeneous catalysts sulfonated graphene oxide and pure
graphene oxide as well as graphite
oxidation in pure GO the percentage of carbon and oxygen changed due to the
oxidation process. In this case pure GO showed 43 % of carbon and 57 % oxygen
percentage homogenously distributed. This increased percentage of oxygen and
decreased percentage of carbon reveals that oxidation occurred on pure graphite and
installation of oxygen functionality such as carboxylic acid, epoxy, and ketone. On
the other side, we have also analyzed GO-SO3H sample, which showed 50 %
carbon, 45 % of oxygen and 4 % of sulfur. The presence of 4 % of sulfur and 45 %
of oxygen in GO-SO3H reveals that covalently functionalization occurred on GO by
sulfonation functionality. In addition, this functionality is homogenously scattered
throughout the sample which conclude homogeneously attachment of HSO3
functionality on GO-HSO3. These characteristics should be facilitate its catalytic
performance, because reactants and products can easily access the active sulfonyl
groups on both sides of the two-dimensional GO-HSO3 with limited mass allocation
resistance.
Catalyst activity
With the sulfonated heterogeneous catalyst GO-HSO3 in hand, one-pot reaction of
benzimidazole synthesis (3) reaction was performed by using Benzene-1,2-diamine
and benzaldehyde representation compounds and optimize the reaction condition.
The results of these studies are summarized in Table 1. First, neat reaction without
catalyst and solvent was performed to determine the reactivity of components.
Negative results were obtained for this reaction up to 24 h stirring (Entry 1). Later
on same reaction was conducted at 90 °C to determine the effect of temperature and
this reaction also resulted in zero yields without any product (Entry 2). However, in
123

Eco-friendly highly efficient solvent free synthesis of…
123

M. B. Swami et al.
next step for the same reaction at room temperature, pure graphite was used as
catalyst to determine the catalytic ability of pure graphite. This reaction showed
18 % conversion and only 5 % selective yield of benzimidazole in 24 h reaction
time (Entry 3). Moreover, reactions were conducted by using catalytic amount of
pure graphene oxide at room temperature in solvent free condition for 12 and 24 h
reaction times. These reactions were also fails to give the efficient yield of
respective products and showed 41 and 67 % conversion with 16 and 21 % yield
respectively (Entries 4, 5). These obtained results demonstrate that pure graphite
and graphene oxide is not sufficient as catalyst for the development of benzim-
idazole at room temperature in solvent free condition. In subsequent step, we tested
0.5 equiv. of GO-HSO3 for the same reaction under solvent free condition at room
temperature. This reaction showed marvelous production of benzimidazole in very
short reaction time. 100 % conversion with 91 % selective formation of benzim-
idazole was obtained in 2 h reaction time in solvent free condition at room
temperature (Entry 6). Then we tried to reduce the amount of the catalyst, the
reactions required the little longer time with reduction of catalyst amount. 0.3 equiv.
catalysts showed 100 % in 4 h reaction time and obtained 90 % yield (Entry 7).
Moreover 0.1 equiv. catalysts showed approximately same yield (89 %) in 7 h
reaction time (Entry 8). Therefore for further application of this prepared GO-HSO3
catalyst 0.1 equiv. of catalytic amount was applied. However the present protocol is
highly efficient in solvent free condition, but determination of solvent effect is still
necessary for the catalytic application at large scale production of benzimidazole.
Therefore, we have tested many solvents for this protocol at room temperature.
Initially methanol was tested which showed 100 % conversion but gave only 57 %
yield in 12 h reaction duration (Entry 9). In addition to that DCM and acetonitrile as
solvent, these solvent also fails to give efficient yield. Results showed that, these
solvent acquired 100 % conversion but showed only 61 and 38 % yield of
respective benzimidazole (Entries 10, 11). However, when reactions were
conducted in all above reactions number of side products were detected, due to
this reason they fail to give efficient selective yield of benzimidazole.
To compare the remarkable catalytic activity of GO-HSO3 catalyst with other
reported heterogeneous catalyst, we conducted model benzimidazole synthesis
reaction using optimized reaction condition and the results are shown in Table 2.
Entries 1 and 2 show benzimidazole synthesis using heterogeneous AlCl3 and FeCl3
in solvent free condition. These reactions were preceded very sluggishly and
provide only 66 and 41 % of respective benzimidazole product respectively after
8 h. However, it is very hard to separate the catalyst and obtained products with
these metal chlorides. Next, we carried out same reaction using CuCl2Á2H2O in
solvent free condition to demonstrate the catalytic role of CuCl2Á2H2O in this
protocol. We observed that catalyst CuCl2Á2H2O (0.1 equiv) was unable to give
selective yield of benzimidazole in optimized condition and resulted 31 % yield
with 82 % conversion (entry 3). While, NiCl2 and CoCl2Á6H2O were produced 47
and 51 % yield of benzimidazole with 100 % conversion (entries 4 and 5). In
addition, we have also carried out reactions with heterogeneous catalyst Co(NO3)2-
6H2O and Ni(NO3)2Á6H2O in optimized reaction condition in solvent free
conditions. Both these catalysts were fails to give efficient yield of product in
123

Eco-friendly highly efficient solvent free synthesis of…
123

M. B. Swami et al.
24 h reaction time. As a results these catalyst showed 32 and 48 % yield with 88
and 61 % conversion respectively (Entries 6 and 7). Finally, to confirm the catalytic
role of Al (NO3)3 in optimized condition, we carried out same reaction in solvent
free condition and this reaction was unable to produce high yield of benzimidazole
even after 18 h. This reaction produced 28 % yield with 57 % conversion (Entry 8).
These reactions results clearly indicate that prepared GO-HSO3 catalyst in solvent
free condition having high selective catalytic ability for the preparation of
benzimidazole in high yield by consuming di-amine and aldehyde (Entry 9).
With effectively preparation and compared catalytic activity in replica compound
benzimidazole 3 preparations by using different heterogeneous catalysts, we
decided to investigate the possibility and simplification of this GO-HSO3 catalyst
reaction in the synthesis of other different benzimidazole with various substituents
on the aromatic rings. Consequently, a diversity of commercially accessible
substituted various 1,2 di-amines and different structurally substituted aldehydes
were treated underneath the optimized reaction conditions for benzimidazole
synthesis and results are summarized in Table 3. As marked from Table 3, all
substituted 1,2 di-amines and aldehydes participated well in this cyclization reaction
and affording the desired products of benzimidazole in good to efficient yields. In
addition these reactions were completed in short reaction time and small amount of
catalyst offered high to efficient yield. Initially without substituted diamine
benzimidazole benzene-1,2-diamine was reacted with benzaldehyde in presence of
0.1 equiv. of catalyst which showed 89 % selective yield of respective benzimi-
dazole in 7 h reaction time (Entry 1). Soon after, reactions were performed using
electron donating organic group substituted diamine 4-methyl-benzene-1,2-diamine
with unsubstituted benzaldehyde moiety which gave 74 % competent yield of
particular benzimidazole in 3 h (Entry 2). In addition, reaction was also preceded
very well with electro donating present on the while using the aldehyde which also
resulted respective efficient yield of benzimidazole (Entry 3). Electro donating
substituted diamine as well as aldehyde was reacted smoothly and obtained 69 %
yield (Entry 4). Electro donating groups such as methoxy group functionalized
substituted di-amine as well as aldehydes were also showed outstanding results with
sulfonated graphene. As a results electro donating group substituted diamines
showed 67 and 78 % yield of respective benzimidazole (Entries 5, 6 and 7). In
further step chloro substituted electron withdrawing group substituted diamines
were showed 81 and 83 % yield of respective benzimidazole in short reaction time
using 0.1 equiv. sulfonated graphene oxide as catalyst (Entries 8 and 9). In addition,
with aldehyde and nitro group substituted diamine were also performed reaction
efficiently and obtained quantitative yield (Entries 10 and 11). However, from these
results it can conclude that, sulfonated functionalized graphene oxide is highly
suitable catalyst for the synthesis of benzimidazole with any functional substitution
on the aromatic rings. In addition, these substituted functionalities were preserved
throughout the course of reaction in presence of prepared catalyst in optimized
reaction condition.
123

Eco-friendly highly efficient solvent free synthesis of…
Table 3 Synthesis of different substituted benzimidazole derivatives using sulfonated graphene oxide in
optimized reaction condition
Time
(h)
Yield
a (%)
Sr. no.
1
Diamine
Aldehyde
Product
7.0
3.0
89
74
2
3
4.0
6.0
81
69
67
78
4
5
6
10.0
6.0
7
4.5
83
8
9
7.0
6.0
81
83
10
11
9
8
78
81
All reactions were carried out on 1.0 mmol of diamine and 1.0 mmol of aldehyde using catalytic amount
of catalyst in solvent free condition
a
Yield refers to the isolated product, characterized by 1H and 13C NMR, and FT-IR
123

M. B. Swami et al.
Scheme 2 Proposed reaction mechanism for the formation of benzimidazole using sulfonated graphene
oxide as heterogeneous catalyst
Proposed reaction mechanism
In order to understand in depth reaction mechanism with GO-HSO3 catalyst on the
basis of obtained results in this study, a plausible reaction mechanism constructed
for the development of benzimidazole derivatives is depicted in Scheme 2. It is
proposed that initially acidic proton of sulfonic group present on surface of
sulfonated graphene oxide gets interaction with the oxygen which is present in
aldehyde functionality, which activates carbonyl group to generate the carbonium
ion, facilitating nucleophilic attack by diamine resulting in imine [33, 34]. The
resulting imine eventually undergoes ring closure by the intramolecular attack of
second amino group and subsequently undergoes aromatization to afford the desired
benzimidazole.
Recyclability test of sulfonated graphene oxide catalyst
It is highly significant to consider the recyclability of heterogeneous catalysts to
understand its lifetime activity for particular reaction, especially for industrial,
pharmaceutical and engineering applications [36–39]. Therefore, it is very essential
to figure out the stability of heterogeneous catalyst under solvent free reaction
conditions. To understand and study the reusability of prepared catalyst, solid GO-
HSO3 catalyst was filtered out from the reaction mixture by means of straightfor-
ward filtration procedure and catalyst rinsed three successive times with de-ionized
123

Eco-friendly highly efficient solvent free synthesis of…
100
a
80
60
40
20
0
1
2
3
4
5
6
Cycle
c
b
100 nm
100 nm
Fig. 7 Recyclability test of sulfonated graphene oxide in benzimidazole synthesis in optimized reaction
condition in solvent free condition (a). TEM analysis of fresh catalyst (b) and after 6th recycled catalyst
(c)
H2O and after drying in vacuum oven catalyst reused in subsequent attempts of
reactions. Recyclability of GO-HSO3 catalyst was studied over six cycles for the
synthesis of benzimidazole under solvent free condition at room temperature. No
significant loss in the yield and selectivity of product was observed over six cycles
(Fig. 7a). Furthermore, conversion of reactant was 100 % and the yield of product
was maintained constant at 82.0 % during recycling tests. In addition morphology
determination of fresh catalyst and after 6th recycled run catalyst did not show
much variation in morphology (Fig. 7b, c) and graphene sheets morphology still
remains constant even after 6th successive runs.
Therefore, the catalyst GO-HSO3 can be competently recycled for six times
without significant failure in its catalytic activity as well as selectivity in the
preparation of benzimidazole by means of solvent free condition. These results
123

M. B. Swami et al.
indicate that, the present methodology is highly eco-friendly and green approach for
the preparation of benzimidazole derivatives.
Conclusions
In conclusion, sulfonated graphene oxide (GO-HSO3) was utilized as a heteroge-
neous catalyst for the synthesis of various substituted benzimidazole at room
temperature for the development of a simple and competent one-pot solvent free
method. The heterogeneous catalyst GO-HSO3 was prepared and characterized by
using fancy analytical and spectroscopic methods which showed that efficient
grafting of the sulfonation groups are occurred over oxidized graphene oxide by
simple sulfonation methods. These grafted special sulfonation groups on prepared
graphene oxide, highly improved sufficient acidity of catalyst which showed the
tremendous positive effect in the yield benzimidazole at room temperature in
solvent free condition. Using 0.1 equiv. amount of catalyst obtained 100 %
conversion and up to 89 % yield. In addition catalyst could be recycled up to six
cycles over sulfonated graphene oxide without damaging selectivity and yield of
benzimidazole. Simplicity of operation, heterogeneity of catalyst, high yields, easy
work-up and purification of compounds, without reaction temperature, and solvent
free condition are the key advantages of this method.
Acknowledgments Authors would like to thanks Council of Scientific and Industrial Research (CSIR),
New Delhi, India for the Junior Research Fellowship (JRF) and Senior Research Fellowship (SRF)
program for financial support. Authors also would like to thanks for the research facility provided by Dr.
Jeong Gil Seo, via through the National Research Foundation of Korea (NRF) funded by the Ministry of
Education (No. 2009-0093816) and Myongji Research Fund-2014.
References
1. M. Hranjec, I. Piantanida, M. Kralj, L. Suman, K. Pavelic, G.K. Zamola, J. Med. Chem. 51, 4899
(2008)
2. K. Yoshida, J. Chem. Soc. Chem. Commun., 1108 (1978)
3. H.J. Seo, M. Song, S.H. Jin, J.H. Choi, S.J. Yun, Y.I. Kim, RSC Adv. 1, 755 (2011)
4. D.D. Sun, W.Z. Wang, J.W. Mao, W.J. Mei, J. Liu, Bioorg. Med. Chem. Lett. 22, 102 (2012)
5. L.B. Leroy, J.C. Drach, U.S. Patent US6455506 B1 (US 09/124,484), 2002
6. P.K. Ranjith, P. Rajeesh, K.R. Haridas, N.Y. Susanta, T.N. Guru Row, R. Rishikesan, N. Suchetha
Kumari, Bioorg. Med. Chem. Lett. 23, 5228 (2013)
7. M.D. Poeta, W.A. Schell, C.C. Dykstra, S. Jones, R.R. Tidwell, A. Czarny, M. Bajic, M. Bajic, A.
Kumar, D. Boykin, J.R. Perfect, Antimicrob. Agents Chemother. 42, 2495 (1998)
8. Y. Tong, J.J. Bouska, P.A. Ellis, E.F. Johnson, J. Leverson, X. Liu, P.A. Marcotte, A.M. Olson, D.J.
Osterling, M. Przytulinska, L.E. Rodriguez, Y. Shi, N. Soni, J. Stavropoulos, S. Thomas, C.K.
Donawho, D.J. Frost, Y. Luo, V.L. Giranda, T.D. Penning, J. Med. Chem. 52, 6803 (2009)
9. R. Lemura, T. Kawashima, T. Fukuda, K. Ito, G. Tsukamoto, J. Heterocycl. Chem. 24, 31 (2009)
10. M.C. Sharma, D.V. Kohli, Arabian J. Chem. (2011). doi:10.1016/j.arabjc.2011.04.016
11. S.M. Sondhi, N. Singh, A. Kumar, O. Lozach, L. Meijer, Bioorg. Med. Chem. 14, 3758 (2006)
12. T. Iwahi, H. Satoh, M. Nakao, T. Iwasaki, T. Yamazaki, K. Kubo, T. Tamura, A. Imada, Antimicrob.
Agents Chemother. 35, 490 (1991)
13. H.A. Barker, R.D. Smyth, H. Weissbach, J.I. Toohey, J.N. Ladd, B.E. Volcani, J. Biol. Chem. 235,
480 (1960)
123

Eco-friendly highly efficient solvent free synthesis of…
14. M.A. Phillips, J. Chem. Soc., 172 (1928)
15. M. Kidwai, A. Jahan, D. Bhatnagar, J. Chem. Sci. 122, 607 (2012)
16. P. Sun, Z. Hu, J. Heterocycl. Chem. 43, 773 (2006)
17. B. Sadeghi, M.G. Nejad, J. Chem. 2013 (2013) (Article ID: 581465)
18. R. Trivedi, S.K. De, R.A. Gibbs, J. Mol. Catal. A: Chem. 245, 8 (2006)
19. R.G. Jacob, L.G. Dutra, C.S. Radatz, S.R. Mendes, G. Perin, E. Lenardao, Tetrahedron Lett. 50, 1495
(2009)
20. R.K. Kumar, P.V.V. Satyanarayana, S.B. Reddy, Arch. Appl. Sci. Res. 4, 1517 (2012)
21. C. Mukhopadhyay, P.K. Tapaswi, Tetrahedron Lett. 49, 6237 (2008)
22. K. Bahrami, M.M. Khodaei, F. Naali, Synlett 04, 569 (2009)
23. S. Lin, L.H. Yang, Tetrahedron Lett. 46, 4215 (2005)
24. K.B. Dhopte, R.S. Zambare, A.V. Patwardhana, P.R. Nemade, RSC Adv. 6, 8164 (2016)
25. R.S. Harapanhalli, L.W. McLaughlin, R.W. Howell, D.V. Rao, S.J. Adelstein, A.I. Kassis, J. Med.
Chem. 39, 4804 (1996)
26. J.J. Vanden Eynde, F. Delfosse, P. Lor, Y.V. Haverbeke, Tetrahedron 51, 5813 (1995)
27. A.H. Jadhav, H. Kim, RSC Adv. 3(15), 5131 (2013)
28. A.H. Jadhav, A. Chinnappan, R.H. Patil, W.J. Chung, H. Kim, Chem. Eng. J. 236, 300 (2014)
29. A.H. Jadhav, A. Chinnappan, V. Hiremath, J.G. Seo, J. Nanosci. Nanotechnol. 15(10), 8243 (2015)
30. A.H. Jadhav, A.C. Lim, G.M. Thorat, H.S. Jadhav, J.G. Seo, RSC Adv. 6, 31675 (2016)
31. D.R. Dreyer, S. Park, C.W. Bielawski, R.S. Ruoff, Chem. Soc. Rev. 39, 228 (2010)
32. M.J. Allen, V.C. Tung, R.B. Kaner, Chem. Rev. 110, 132 (2010)
33. M. Mirza-Aghayan, R. Boukherroub, M. Rahimifard, Turk. J. Chem. 38, 859 (2014)
34. M. Mirza-Aghayan, M. Alizadeh, M.M. Tavana, R. Boukherroub, Tetrahedron Lett. 55, 6694 (2014)
35. M.M. Aghayan, M.M. Tavana, R. Boukherroub, Ultrason. Sonochem. 29, 371 (2016)
36. J. Ji, G. Zhang, H. Chen, S. Wang, G. Zhang, F. Zhang, X. Fan, Chem. Sci. 2, 484 (2011)
37. A.H. Jadhav, K. Lee, S. Koo, J.G. Seo, RSC Adv. 5(33), 26197 (2015)
38. A.H. Jadhav, G.M. Thorat, K. Lee, A.C. Lim, H. Kang, J.G. Seo, Catal. Today 265, 56 (2016)
39. A.H. Jadhav, A. Chinnappan, R.H. Patil, S.V. Kostjuk, H. Kim, Chem. Eng. J. 240, 228 (2014)
123