Application of sulfonic acid fabricated cobalt ferrite nanoparticles as effective magnetic nanocatalyst for green and facile synthesis of benzimidazoles

Article abstract of DOI:10.1016/j.apcata.2021.118005

This work represents the design and synthesis of efficient sulfonated cobalt ferrite solid acid catalyst. The synthesized solid acid green catalyst was characterized using various techniques viz. FT-IR, powder XRD, SEM, TEM and VSM. The obtained catalyst was used to synthesize biologically significant 2-substituted benzimidazole derivatives by condensation between o-phenylenediamine with various aromatic, aliphatic and heterocyclic aldehydes. High yield (up to 98 %), short reaction time (10?25 min), mild reaction condition, wide functional group tolerance, easy work-up procedure and excellent values of green chemistry metrices such as lower E factor (0.126), high RME value (88.83 %), carbon efficiency (100 %) and high atom economy (AE) value (90.65 %), are some salient features of the present catalytic system. Moreover, the catalyst recovery by simply using an external magnet and catalyst reusability up to 7 times without any significant loss in catalytic efficiency are some additional remarkable features of the current protocol.

Full text of DOI:10.1016/j.apcata.2021.118005

Applied Catalysis A, General 612 (2021) 118005
Contents lists available at ScienceDirect
Applied Catalysis A, General
journal homepage: www.elsevier.com/locate/apcata
Application of sulfonic acid fabricated cobalt ferrite nanoparticles as
effective magnetic nanocatalyst for green and facile synthesis
of benzimidazoles
Priyanka Yadav, Praachi Kakati, Preeti Singh, Satish K. Awasthi*
Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India
A R T I C L E I N F O
A B S T R A C T
Keywords:
This work represents the design and synthesis of efficient sulfonated cobalt ferrite solid acid catalyst. The syn-
thesized solid acid green catalyst was characterized using various techniques viz. FT-IR, powder XRD, SEM, TEM
and VSM. The obtained catalyst was used to synthesize biologically significant 2-substituted benzimidazole
derivatives by condensation between o-phenylenediamine with various aromatic, aliphatic and heterocyclic
aldehydes. High yield (up to 98 %), short reaction time (10ꢀ 25 min), mild reaction condition, wide functional
group tolerance, easy work-up procedure and excellent values of green chemistry metrices such as lower E factor
(0.126), high RME value (88.83 %), carbon efficiency (100 %) and high atom economy (AE) value (90.65 %), are
some salient features of the present catalytic system. Moreover, the catalyst recovery by simply using an external
magnet and catalyst reusability up to 7 times without any significant loss in catalytic efficiency are some
additional remarkable features of the current protocol.
Benzimidazole
Green solvent
Heterogeneous catalyst
Reusability
Solid acid
1. Introduction
(carbonitriles, orthoesters), arylamino oximes and cyclization of o-bro-
moaryl derivatives. However, the most efficient and commonly used
Heterocyclic compounds containing nitrogen are considered as sig-
nificant building blocks of various natural products, agrochemicals,
pharmaceuticals, and functionalized advanced materials [1]. Among
these benzimidazole have emerged as privileged class of N-heterocycles
having wide range of applications in pharmaceuticals. They display
numerous biological activities and are used as antimicrobial [2],
anti-inflammatory [3], antibacterial [4], antibiotic, anti-ulcer [1],
anti-cancer [5], anti-helminthic [6], anti-hypertensive [7], topoisom-
erase IV inhibitors [8] and anti-HIV [1]. Some of the successful clinical
drugs containing benzimidazole framework are carbendazim, thiaben-
dazole, omeprazole [9] etc. (Fig. 1).
method is condensation of o-phenylenediamine with aldehyde [9].
Literature survey reveals that there are numerous catalysis like mineral
acids (H2SO4, HNO3 and HF), Lewis acids (AlCl3 and BF3) [13], silver
nanoparticle [14], metal triflate [15], KHSO4, Amberlite, L-proline,
CoCl2, PTSA, solid support catalyst and ionic liquids [16] are used for
the synthesis of benzimidazole synthesis. Even after having these ump-
teen methods of preparation of benzimidazoles, they are linked with
various limitations, such as low atom economy, the formation of
by-product, harsh reaction conditions, extended reaction period,
expensive catalysts, unsatisfactory yield of products as well as toxic
solvents.
The imidazole ring present in benzimidazole scaffold is also a distinct
part of numerous natural products such as histidine, proteins, histamine,
purines and biotin [10]. Along with these, benzimidazole analogs have
applications in dye and pigment industry, chemical UVB filters, chemo
sensors and thermostable membranes used for fuel cells [1,11,12].
Owing to the importance of benzimidazole scaffolds numerous
strategies have been made for their synthesis. Various synthetic schemes
for their development involves aromatic and heteroaromatic 2-nitro-
amines, phenylenediamine, carboxylic acids or its derivatives
Taking into consideration of these constraints, there is an urgent
need to design a new more simple, efficient, cheap and reusable het-
erogeneous catalyst which can be recovered easily from reaction me-
dium and the synthesis of 2-substituted benzimidazoles can be done
efficiently under mild reaction conditions.
In past few years, nanomaterials have been extensively employed as
a solid support material [17] for the designing of heterogeneous catalyst
to overcome the economic and environmental issues. Nanoparticles are
well-thought-out as semi-heterogeneous support as they can be
* Corresponding author.
E-mail address: satishpna@gmail.com (S.K. Awasthi).
https://doi.org/10.1016/j.apcata.2021.118005
Received 11 November 2020; Received in revised form 7 January 2021; Accepted 7 January 2021
Available online 21 January 2021
0926-860X/© 2021 Elsevier B.V. All rights reserved.

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
2. Experimental
2.1. Catalyst preparation
2.1.1. Functionalization of silica-coated CoFe2O4 nanoparticles with amine
groups
The cobalt ferrite nanoparticles (CoFe2O4) were prepared by one-pot
solvothermal process [26]. Briefly, CoCl2⋅6H2O (297.4 mg, 1.25 mmol)
and FeCl3⋅6H2O (676 mg, 2.5 mmol) were taken in 20 mL of ethylene
glycol and stirred continuously at 50 ◦C to obtain a homogeneous
mixture. After that, 1.8 g of sodium acetate (NaOAc) and 1.0 g of
PEG-6000 were added to the above reaction mixture and further stirred
for extra 30 min. The obtained liquid was then moved to a sealed
Teflon-lined stainless steel autoclave and kept for 16 h at 160 ◦C. The
black product obtained was extracted using an external magnet and then
washed several times with double-deionized water. The resultant cobalt
ferrite (CoFe2O4) nanoparticles were then dried for 6 h at 60 ◦C.
The coating of cobalt ferrite nanoparticles (CoFe2O4) by silica was
Fig. 1. Benzimidazole scaffold containing commercial drugs.
dispersed easily and exhibit high surface area [18]. Nanocatalysts being
stable, durable and cost effective, eliminates the need for harsh reaction
conditions, increases energy efficiency, provides high selectivity, and
allows the minimal use of substrates. Among these nanomaterials
magnetically retrievable nanocatalyst made number of heads turn due to
its unique advantages such as easy and fast separation from reaction
media simply by the application of external magnetic field.
¨
achieved using Stober sol–gel method [27]. For this, CoFe2O4 nano-
particles (200 mg, 0.852 mmol) in 200 mL solution (160 mL of ethanol
and 40 mL of double deionized water) were sonicated and then 1.5 mL of
ammonia solution and 1 mL of TEOS were added to the solution in
dropwise manner. The dispersed mixture was then stirred continuously
for 6 h at 60 ◦C. The silica coated nanoparticles (CoFe2O4@SiO2) were
separated magnetically, washed several times with ethanol and dried
under vacuum.
Magnetic cobalt ferrite spinel (CoFe2O4) have attracted a lot of
attention owing to the most prominent support demonstrating wide
application in numerous fields such as in ferrofluids technology, MRI,
biosensors, drug delivery [19], photocatalysis and nanobiotechnology.
They also display exceptional properties like simplistic synthesis, ri-
gidity, high surface area, high abundance of surface hydroxyl groups,
outstanding thermal stability, high chemical steadiness, relatively high
anisotropy, Curie temperature as well as saturation magnetization (Ms)
[20,21]. However, the magnetic nanoparticles has a strong tendency of
aggregation. Thus in order to prevent aggregation, the core is usually
prevented by an external coating of silica, carbon, or gold etc. [22]. The
major advantages of the silica coating are admirable thermal as well as
chemical steadiness, high surface area, adjustable pore size, ease of
handling, and ease of attaching ligands covalently due to high profusion
The NH2 groups onto the surface of CoFe2O4@SiO2, were introduced
by the addition of 1 mL of APTES to 0.5 g of silica coated CoFe2O4
nanoparticles dispersed in 100 mL of ethanol. The resultant solution was
allowed to stir continuously for 6 h at 80 ◦C. The obtained CoFe2O4@-
SiO2@NH2 nanoparticles were magnetically collected, washed several
times using ethanol for the removal of any unreacted silylating agent,
and then allowed to dry under vacuum.
2.1.2. Preparation of biguanidine functionalized nanocomposite (CFNP’s)
In order to increase the catalytic sites, biguanidine moiety was
incorporated on the surface of the nanocomposite. For this, 0.5 g of
CoFe2O4@SiO2@NH2 nanoparticles, 125 mg of dicyanodiamide, 0.3 mL
of triethylamine were added to 10 mL of ethanol and the mixture was
–
of exposed silanol (Si OH) groups [20].
The acid catalysts including mineral acids such as H2SO4, HCl, HF
and organic acids like p-toluene sulfonic acid (PTSA) suffer from various
drawbacks such as corrosion, toxicity, their tedious separation from
homogeneous reaction medium and need of neutralization of waste
streams [23]. Among these commonly used acids, sulfonic acid being
highly active, is proficiently used for synthesizing different organic
compounds. However, owing to its hazardous nature, it is harmful to the
environment as well as public health. It is deadly if swallowed/inhaled
and also cause eye and skin burn. Being highly reactive, it reacts
immediately with water to generate toxic hydrochloride (HCl) and sul-
fur dioxide [24]. Along with these drawbacks, its difficulty of separation
from reaction mixture restricts its pertinency in pharmaceutics and in-
dustry. Keeping all these drawbacks of sulfonic acid in mind, we have
synthesized heterogeneous solid sulfonic acid fabricated over biguani-
dine functionalized silica coated cobalt ferrite nanoparticles for its safer
use. In addition to these, its immiscibility in organic solvents, high air
and thermal stability, chemical stability, easy separation from the re-
action medium, facile recyclability, non-hygroscopic nature, and
excellent catalytic performance makes its utilization feasible in various
fields.
stirred continuously for 6
h at reflux conditions. The resulting
CoFe2O4@SiO2@NH2@BG (CFNP) nanoparticles were separated
magnetically, washed several times with ethanol and dried under vac-
uum for 6 h.
2.1.3. Preparation of final sulfonated CFNP@SO3H nanocatalyst
(CoFe2O4@SiO2@NH2@BG@SO3H)
The final nanocatalyst (CFNP@SO3H) was synthesized by sulfona-
tion of surface amino groups present on CFNP’s (Scheme 1 and Fig. S1).
Briefly, 0.5 g of CoFe2O4@SiO2@NH2@BG (CFNP) nanoparticles were
added in 25 mL of dry DCM followed by addition of 2 mL of chlor-
osulfonic acid dropwise within 30 min. The reaction mixture obtained
was subjected to continuous stirring until HCl evolution stops and then
further stirring at room temperature for 12 h to certify complete func-
tionalization. After this, the obtained solid acidic nanocatalyst was
separated using an external magnet and washed several times with
ethanol and deionized water. The resultant nanocatalyst (CFNP@SO3H)
was dried under vacuum for 6 h.
In continuation of our research efforts in designing heterogeneous
solid acid magnetic nanocatalyst for organic transformations [25], here,
we wish to report the synthesis of biologically important 2-substituted
benzimidazoles by condensation between o-phenylenediamine and
aryl aldehydes using CoFe2O4@SiO2@NH2@BG@SO3H (CFNP@SO3H)
nanoparticles as heterogeneous catalyst.
2.2. General method for synthesis of 2-substituted benzimidazole
derivatives
To a equimolar mixture of o-phenylenediamine (1.0 mmol), benz-
aldehyde (1.0 mmol) in 3 mL of ethanol, 20 mg of nanocatalyst
(CFNP@SO3H) was added and the reaction solution was subjected to
continuous magnetic stirring at room temperature. The reaction prog-
ress was closely monitored using TLC and after the verification of
2

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
Scheme 1. Systematic representation for the synthesis of CFNP@SO3H magnetic nanoparticles.
completion of reaction, the catalyst was removed from reaction mixture
using an external magnet. After this, ice cold water was added to the
reaction mixture leading to the formation of a precipitate. The crude
product in form of precipitate formed was filtered off and dried. The
crude product was then recrystallized using ethanol to afford the pure
product.
signifies the FT-IR spectra of CFNP and CFNP@SO3H nanoparticles
respectively. The appearance of two new peaks at 1087 cmꢀ 1 and 985
cmꢀ 1 corresponds to the asymmetrical and symmetrical stretching vi-
–
bration of S O bond in CFNP@SO H, respectively (Fig. 2e). Thus the
–
3
obtained results confirmed the successful functionalization with desired
amino moiety along with the sulfonic acid group in silica coated cobalt
ferrite nanoparticles.
3. Results and discussion
3.1.2. XRD analysis
In order to comprehend the structural integrity and crystalline phase
structure of synthesized nanoparticles, X-Ray Diffraction patterns of
CoFe2O4, CoFe2O4@SiO2, and CoFe2O4@SiO2@NH2@BG@SO3H
(CFNP@SO3H) were obtained in the 2Ɵ range of 5ꢀ 80◦ at room tem-
perature (Fig. 3). The distinctive Bragg diffraction peaks appearing at
30.24, 35.62, 43.33, 53.60, 57.27, and 62.79◦ can be assignable to
(220), (311), (400), (422), (511), and (440) planes of the spinel cobalt
ferrite nanoparticles. The observed peaks match very well with the
standard XRD data of JCPDS card number (22–1086). Furthermore, the
Bragg peaks for silica coated CoFe2O4 and CFNP@SO3H were observed
at same 2θ values as for CoFe2O4, confirming that the structure of
CoFe2O4 nanoparticles remained intact even after surface modification.
3.1. Catalyst characterization
3.1.1. FT-IR spectroscopy
FT-IR spectra of CoFe2O4, CoFe2O4@SiO2, CoFe2O4@SiO2@NH2,
CFNP and CFNP@SO3H were collected at room temperature within
range of 400–4000 cmꢀ 1, as depicted in Fig. 2.
The spectra of CoFe2O4 nanoparticles visibly shows two absorption
bands appearing at 881 and 547 cmꢀ 1, that can be allocated to the
–
–
Co O and Fe O vibrations, whereas, the broad bands appeared around
3404 and 1648 cmꢀ 1 are attributed to the stretching and bending vi-
brations respectively of the surface hydroxyl groups present (Fig. 2a).
Further, the bands appearing at 792, 950, and 1068 cmꢀ 1 in the spectra
– –
–
O
of CoFe2O4@Si can be assigned to the Si
O
Si symmetric, Si
3.1.3. SEM and TEM analysis
– –
symmetric, and Si
O Si asymmetric stretching modes, confirming
The morphology of nanoparticles and their texture depiction was
achieved by SEM and TEM analysis of synthesized CoFe2O4,
CoFe2O4@SiO2, and CFNP@SO3H nanoparticles and are shown in Fig. 4.
The obtained SEM images for CoFe2O4 corroborated the monodisperse
nature as well as the formation of spherically shaped nanoparticles
existence of silica over the surface of CoFe2O4 nanoparticles (Fig. 2b).
For amine functionalized CoFe2O4@SiO2 nanoparticles, two new bands
appearing at 2920 and 1642 cmꢀ 1, can be ascribed to the CH2 and amine
groups, respectively, further confirming the functionalization of silica
coated nanoparticles with NH2 groups (Fig. 2c). Further, Fig. 2d and e
Fig. 2. FT-IR spectra results of (a) CoFe2O4, (b) CoFe2O4@SiO2, (c)
Fig. 3. Powder XRD spectrum of (a) CoFe2O4, (b) CoFe2O4@SiO2 and
CoFe2O4@SiO2@NH2, (d) CFNP and (e) CFNP@SO3H.
(c) CFNP@SO3H.
3

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
Fig. 4. SEM images of (a) CoFe2O4, (b) CoFe2O4@SiO2, (c) CFNP@SO3H and TEM images of (d) CoFe2O4, (e) CoFe2O4@SiO2, (f) CFNP@SO3H.
(Fig. 4a). Further, SEM analysis of silica coated and surface modified
nanoparticles depicts the spherical shape of these nanoparticles (Fig. 4b
and c). TEM analysis of these nanoparticles was also done revealing the
spherical shape of CoFe2O4 nanoparticles having a diameter approxi-
mately 200 nm (Fig. 4d). The EDX was also obtained for CoFe2O4 which
confirms the presence of Fe, Co and O as represented in (Fig. S1). TEM
imaging of silica coated CoFe2O4 nanoparticles validates the existence of
approximately 30 nm uniform silica layer around the CoFe2O4 core
(Fig. 4e), preventing them from agglomeration. Furthermore, the TEM
image of CFNP@SO3H substantiated the intact of similar spherical
morphology along with an increase in the size of these nanoparticles
(Fig. 4f).
3.1.4. Brunauer-Emmett-Teller (BET) surface area analysis
The N2 adsorption-desorption isotherm was collected using BET
analysis of solid acid catalyst (CFNP@SO3H) (Fig. 6) to determine the
textural properties and to understand its porosity. The nanocatalyst
showed BET surface area of 30.966 m2/g. The average pore diameter
and pore volume determined using Barrett-Joyner- Halenda (BJH) were
4.88 nm and 0.0527 cm3/g, respectively (inset, Fig. 6). The pore
diameter obtained indicated toward the mesoporous nature of the solid
acid catalyst, Further, the existence of hysteresis loop in N2 adsorption-
desorption isotherm for CFNP@SO3H confirmed its mesoporous nature.
The low pore volume can be due to presence of SO3H moieties in the
pores of CFNP nanoparticles. Thus, the solid acid catalyst possessed
sufficient surface on which the active sites were well dispersed, allowing
them easily available to the reactants.
Further, to gain knowledge of the stoichiometric distribution of el-
ements in the synthesized CFNP@SO3H nanocatalyst, its EDX spectrum
was collected. The obtained EDX spectrum revealed the presence of
expected constituent elements like iron, cobalt, oxygen, silicon, carbon,
nitrogen and sulfur in the sample (Fig. 5), further confirming the desired
fabrication of nanocatalyst by acidic sulfonic group.
3.1.5. VSM analysis
Magnetization of synthesized CoFe2O4, CoFe2O4@SiO2, CoFe2O4@
SiO2@NH2, CFNP and CFNP@SO3H were assessed using vibration
sample magnetometer (VSM) at room temperature (Fig. 7). The
magnetization values of the bare as well as functionalized nanoparticles
Fig. 5. EDX of CFNP@SO3H.
4

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
with a slight shaking. Thus, the present solid acid catalyst demonstrates
fast response to an external magnetic force and as a result, it can be
collected effortlessly from the reaction medium, making it favourable
for practical applications.
3.2. Catalytic activity evaluation of the sulfonated cobalt ferrite
nanocatalyst in the synthesis of benzimidazoles
The catalytic ability of the synthesized sulfonated magnetic nano-
catalyst (CFNP@SO3H) was explored in the synthesis of benzimidazole
via a one-pot condensation reaction between o-phenylenediamine and
benzaldehyde taking them as model substrates. Thereafter, the impact of
various conditions such as amount of catalyst (CFNP@SO3H), solvent,
and time period for the completion of reaction were studied in order to
attain the best reaction conditions.
3.2.1. Effect of catalyst amount on synthesis of benzimidazoles
Fig. 6. N2 adsorption-desorption isotherm of CFNP@SO3H. Inset: pore size
In order to optimize our reaction conditions we started our investi-
gation by exploring the role of synthesized sulfonated nanocatalyst in
the synthesis of 2-substituted benzimidazoles. For achieving this goal, an
equimolar mixture (1 mmol) of both the substrates were taken in the
absence of nanocatalyst. The product was observed in trace amounts
when the reaction was performed in the absence of catalyst suggesting
the importance of catalyst to afford the high yield of desired benz-
imidazole product. Afterwards, to investigate the effect of amount of
catalyst on the reaction, the chosen reaction of o-phenylenediamine and
benzaldehyde was performed in the presence of a varying amount of
synthesized sulfonated cobalt ferrite nanocatalyst (CFNP@SO3H). A
remarkable increase in the yield with the reduction in time period for
formation of benzimidazole product was observed when the amount of
catalyst was increased from 5 mg to 20 mg which is attributed to the
increase in number of the active catalytic sites (Fig. 8). Further, no such
increase in conversion percentage was observed after additional incre-
ment up to 25 mg, owing to the exhaustion of active catalytic sites. Thus,
20 mg of catalyst was fixed for the maximum conversion and for further
experiments.
distribution of CFNP@SO3H nanoparticles.
3.2.2. Effect of solvents
Fig. 7. Magnetization curves obtained through VSM at room temperature for
(a) CoFe2O4, (b) CoFe2O4@SiO2, (c) amine functionalized CoFe2O4@SiO2, (d)
CFNP and (e) CFNP@SO3H. Inset: Separation of nanocatalyst using an
external magnet.
It was observed that the nature of solvent has a remarkable effect on
the product formation. Solvents possess the ability to alter the reaction
environment by changing the solubility of reagents, polarity and
dispersing the catalyst. In order to achieve the excellent catalytic con-
were measured in the presence of an external field sweeping between
ꢀ 10,000 and 10,000 Oe at room temperature. The absence of hysteresis
phenomenon and coercivity in all cases illustrated the super-
paramagnetic nature of these synthesized nanoparticles. The value of
saturation magnetization (Ms) for CoFe2O4, CoFe2O4@SiO2,
CoFe2O4@SiO2@NH2, CFNP nanoparticles and for the final catalyst
(CFNP@SO3H) were found to be 63, 52, 47, 34 and 27 emu/g, respec-
tively. The decrease in values of saturation magnetization was observed
on going from bare to surface modified nanoparticles. This decrease in
the value of magnetism is owing to the fact of presence of non magn
nonmagnetic silica and immobilization of various functional groups
which results in reduction of the surface moments of individual particles
[27]. In spite of the lower Ms value for the final catalyst, it is still sig-
nificant and sufficient to attract CFNP@SO3H NPs from solution quickly
upon application of the external magnetic field. The magnetic hysteresis
measurement of recovered catalyst was also performed at room tem-
perature and Ms value for these came out to be ~19 emu/g, meaning
that their recovery can be done efficiently and easily using an external
magnet. Further, the magnetic solid acid catalyst (CFNP@SO3H) in re-
action mixture can be dispersed easily simply by shaking resulting in the
production of black coloured suspension. While, when an external
magnet was used, the nanoparticles aggregates quickly within 30 s. Once
the external magnet was detached, the nanoparticles redispersed quickly
version,
various
solvents
such
as
ethanol,
acetonitrile,
Fig. 8. Effect of amount of catalyst on the synthesis of benzimidazole. [Reac-
tion conditions: o-phenylenediamine (1.0 mmol), benzaldehyde (1.0 mmol),
solvent (3 mL), rt].
5

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
dimethylformamide, water, chloroform, and dioxane for various time
period were tested for the CFNP@SO3H catalysed formation of benz-
imidazoles (Fig. 9). After a close inspection of all obtained results, it was
concluded that polar solvents such as ethanol, acetonitrile, water etc.
resulted in increase of product yield as compared to non-polar solvents
such as dioxane. On comparing results, ethanol was found to be the best
solvent for the effective conversion of benzimidazoles in a shorter time
period. The other reason for increase in yield of product in ethanol
medium is better dispersion of nanocatalyst in this solvent. In order to
prove that, the size distribution of CFNP@SO3H nanoparticles dispersed
in various solvent was also determined using DLS experiment. The
average size of these nanoparticles in ethanol determined by DLS studies
came about 250 nm (Fig. 10) revealing that well dispersion of nano-
particles in ethanol which resulted in large surface area. The average
size of nanoparticles obtained in ethanol medium is in well agreement
with TEM results, whereas in case of other solvents like chloroform,
water, dioxane etc. the average size was larger due to formation of ag-
gregates (Fig. S6), which resulted in decrease in surface area of nano-
partcles and thus decrease in yield of product. Further, ethanol being a
green solvent, generation of waste was minimized and green chemistry
parameters were followed. Hence, subsequent reactions were performed
in an ethanol medium to obtain the desired products.
Fig. 10. DLS size distribution curve of CFNP@SO3H nanoparticles dispersed
in ethanol.
Table 1
Evaluation of Green Chemistry Metrices.
Yield
98 %
atom economy
(AE)
reaction mass
E-
carbon efficiency
(CE)
efficiency (RME)
factor
90.65
88.83 %
0.126
100 %
3.2.3. Green chemistry parameters
The green chemistry metrices for the synthesis of model benzimid-
azole product were also inspected. Several parameters involved for the
assessment of green approach in organic synthesis under optimized
conditions are outlined in Table 1. The radar chart diagram among E-
factor, atom economy, reaction mass efficiency and carbon efficiency
displays a synergistic relationship between all these parameters, indi-
cating the environmental sustainability of the current protocol (Fig. 11).
All the calculations related to green chemistry parameters are described
in supporting information file.
3.2.4. Scope of synthesis of 2-Substitututed benzimidazole derivatives using
CoFe2O4@Si@NH2@BG@SO3H (CFNP@SO3H) nanoparticles
Based on the optimized reaction conditions, the synthesized sulfo-
nated nanocatalyst was used to synthesize benzimidazole derivatives by
condensation between o-phenylenediamine and various benzaldehydes.
For this a mixture of o-phenylenediamine (1.0 mmol), benzaldehyde
(1.0 mmol) and catalyst (20 mg) in 3 mL ethanol were allowed to react at
room temperature for a specific period of time. A diverse range of
valuable 2-substituted benzimidazole derivatives were synthesized in
good to excellent yield by using various substituted benzaldehydes and
aliphatic aldehydes. It was observed that the time period for completion
of reaction and yield of product depends upon the electronic environ-
ment of the benzaldehydes used. The benzaldehyde derivatives having
electron donating groups, the reaction proceeded in shorter period of
Fig. 11. Radar chart plot of green chemistry metrices calculated for the syn-
thesis of model reaction product “3a” (For interpretation of the references to
colour in this figure legend, the reader is referred to the web version of
this article).
time in comparison to the benzaldehydes having electron withdrawing
groups (Scheme 2). Further, along with aromatic aldehydes, aliphatic
aldehyde were also used to obtain benzimidazole derivatives in excel-
lent yield (3p and 3q). In addition to benzaldehyde derivatives, the re-
action of o-phenylenediamine with heteroatomic aldehyde (2 m) was
also performed leading to the formation of the desired product (3 m) in
good yield in slight longer reaction time period (25 min).
Further, the synthesis of benzimidazole (3a) was done at gram level
for industrial point of view. In order to achieve that o-phenylenediamine
(1) (10 mmol), and benzaldehyde (2a) (10 mmol) were allowed to react
in ethanol medium in presence of 150 mg catalyst (CFNP@SO3H). It was
observed that reaction proceeded smoothly and 1.7 g of 2-phenylbenzi-
midazole product could be synthesized within 1 h. Thus, the ability of
the present catalytic system to scale up the reaction under milder re-
action conditions and easy workup procedure are the additional ad-
vantages of current approach.
3.2.5. Plausible reaction mechanism
A plausible mechanism for CFNP@SO3H catalysed formation of 2-
substituted benzimidazoles has been depicted in Fig. 12. Firstly, the
solid sulfonated acidic catalyst protonates the oxygen atom of the
carbonyl group of aromatic aldehyde resulting in an increase of elec-
trophilicity of carbonyl atom. This facilitates the activity of aromatic
Fig. 9. Effect of various solvents and time period on the formation of benz-
imidazoles. [Reaction conditions: o-phenylenediamine (1.0 mmol), benzalde-
hyde (1.0 mmol) and catalyst (20 mg), rt].
6

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
Scheme 2. Substrate scope for the synthesis of 2-substituted benzimidazoles.
3.2.6. Quantification of sulfonic acid loading on CFNP@SO3H
In order to determine the amount of acid over the surface of catalyst
(CFNP@SO3H), simple back titration method was employed. Briefly,
exactly 10 mg of CFNP@SO3H nanocatalyst was added to 10 mL
aqueous KCl solution (1 M) and the resultant mixture was subjected to
sonication for half an hour. Afterwards, the pH of the resultant solution
reduced to 2, demonstrating an ion exchange took place between pro-
tons of nanocatalyst and the potassium ions. Later on, the magnetic
nanocatalyst was collected from the mixture with the help of an external
magnet, and remaining supernatant was subjected to analysis. 2ꢀ 3
drops of phenolphthalein indicator solution was added to collected su-
pernatant and titrated with standardized 0.1 M KOH solution, till the
neutralization point is reached, to evaluate the active acid amount on
the magnetic nanocatalyst. The acid amount on the present heteroge-
neous acid catalyst calculated using back titration method came out to
be 2.48 mmol gꢀ 1
.
3.2.7. Investigation of recyclability of magnetic sulfonated cobalt ferrite
(CFNP@SO3H) nanocatalyst
Fig. 12. Plausible reaction mechanism for the synthesis of 2-substituted
benzimidazole using CFNP@SO3H nanoparticles.
Taking into consideration various parameters of green chemistry,
industrial application, recovery and reusability of catalyst are two
utmost essential characteristics that lead towards its large scale appli-
cation. Thus the recyclability of nano catalyst was assayed using o-
phenylenediamine and benzaldehyde as model substrates. After the
completion of the reaction, the catalyst was removed from the reaction
medium by utilizing an external magnet followed by washing with
ethanol and drying at 60 ◦C under vacuo. Afterwards, the recovered
solid acid catalyst was subjected to consecutive runs of the identical
model reaction under the similar reaction conditions. The results of
recycling experiment indicated that the nanocatalyst can be recovered
aldehyde to react with one NH2 group of o-phenylenediamine to form
Schiff’s base. Then, the second NH2 group of o-phenylenediamine do-
nates a lone pair of electron to carbon of the intermediate resulting in
formation of five membered ring through intramolecular ring closing.
The proton of the positively charged N was abstracted by the negatively
charged catalyst resulting in regeneration of sulfonated catalyst. The
intermediate thus formed, produces 2-substituted benzimidazole
through removal of H+ ions in presence of atmospheric oxygen.
7

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
indicating towards the stability and durability of the catalyst.
3.2.8. Comparison of CFNP@SO3H catalysed formation of 2-Substituted
benzimidazoles with reported precedents
An extensive literature survey suggests that various homogeneous as
well as heterogeneous catalysts have been described for the formation of
2-substituted benzimidazoles (Table 2). Despite of all these, magnetic
solid acid CFNP@SO3H nanocatalyst exhibited its predominance in
terms of ambient reaction conditions, catalyst loading, time period,
product yield, extensive functional group tolerance, catalytic magnetic
retrievability and recyclability. The outstanding performance of the
present magnetic solid acid nanocatalyst is due to the existence of large
number of sulfonated catalytic sites responsible for the formation of the
desired product. Therefore, the present catalytic system presents a clean
and green approach using ethanol an environmental benign solvent,
easy work up procedure and recyclability of sulfonated nanocatalyst by
simply applying magnetic forces.
Fig. 13. Recyclability of synthesized CFNP@SO3H catalyst for the model re-
action under same reaction conditions.
effortlessly and also can be reused for seven successive cycles deprived
of any considerable loss of its catalytic activity (Fig. 13). The slight
decrease in the activity of the catalyst can be attributed to the pore
blockage with reactants or products. Further, to confirm the true het-
erogeneous nature of catalyst and to investigate the leaching of acidic
SO3H group into the reaction mixture, the solid acid catalyst
(CFNP@SO3H) was detached from the reaction medium using an
external magnet after 4 min. The remaining reaction solution was
permitted to react further under similar reaction conditions. This ex-
periments exhibited that no further reaction progress was detected even
after 20 min (Fig. S7), whereas the unperturbed reaction showed the
continuous increase in yield of benzimidazole product. Thus leaching
experiment results demonstrated the heterogeneous nature of present
catalyst and indicated towards the absence of any catalytic active spe-
cies in the filtrate which proves the stability of sulfonated group over the
surface of nanoparticles. The results was further verified by the Powder
XRD, SEM and TEM of the catalyst collected after the 7th run (sup-
porting information). On comparing results of fresh and recovered
catalyst it was revealed that the structure and morphology of the acidic
nanocatalyst remained almost unaffected even after seven runs
4. Conclusions
In summary, we have explored the performance of newly developed
sulfonated magnetic cobalt ferrite nanocatalyst (CFNP@SO3H) for the
synthesis of biologically important 2-substituted benzimidazoles. The
salient features of the present protocol includes ambient reaction con-
ditions, shorter reaction period (10ꢀ 25 min), low catalyst loading,
broad substrate scope and high yield of products. Along with these, the
nanocatalyst can be recovered easily from the reaction mixture by
simple magnetic attraction as it displayed saturation magnetization
value of 27 emu/g and possess recyclability up to 7 consecutive cycles
without any significant loss in activity. In addition, reaction simplicity,
the use of non-toxic chemicals, cost, use of environment benign solvent
“ethanol”, and simple workup procedure make this methodology a green
and sustainable approach for the large scale synthesis of 2-substituted
benzimidazoles. Further, we are in opinion that the developed nano-
catalyst has the flexibility of immobilizing various chemical moieties
onto it which could promote several other industrially substantial
organic transformation reactions in an environmentally benign
conditions.
Table 2
CRediT authorship contribution statement
Previously reported methods and catalyst for the formation of benzimidazoles.
S.
Catalyst
Solvent/Temp
Reaction
time/ Yield
(%)
Ref.
Priyanka Yadav: Conceptualization, Methodology, Software, Visu-
alization, Writing - original draft. Praachi Kakati: Software, Validation,
Writing - review & editing. Preeti Singh: Writing - original draft,
Writing - review & editing. Satish K. Awasthi: Supervision.
No.
1.
2.
3.
[NiL1(PPh3)] (0.5 mol%)
NaHSO3
Ethanol/rt
2ꢀ 3 h/94 %
95 %
[1]
DMF/80 ◦
C
[28]
[29]
Graphene oxide (20 mg)
Methanol/60
3 h/82 %
◦C
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
4.
Resin Supported Ionic Liquids/
Iodide and BPO as oxidant (0.2
equiv.)
Water/rt
5 h/95 %
[30]
5.
6.
PBA@SMNP
Ethanol/50 ◦
Ethanol/40 ◦
C
30 min/95 %
50 min/95 %
[31]
[9]
Sulfonated carbon-
encapsulated iron
nanoparticles
C
PY and PS acknowledges University Grant Commission, Delhi, India,
for awarding Senior Research Fellowship. The authors acknowledges
USIC, University of Delhi, Delhi, for providing instrumentation facilities.
Authors also acknowledges SAIF, AIIMS New Delhi, for TEM facility.
SKA acknowledges financial support from DST-SERB (SERB/F/
9974T20-17), New Delhi, India.
7.
8.
{Mo72V30} (0.05 mol%)
EtOAc, O2
4 h/95 %
[32]
[33]
balloon/ 70 ◦
Toluene/160
◦C
C
Pd(dppf)Cl2
24 h/97 %
9.
Ce(NO3)3.6H2O
DMF/80 ◦
C
90 min/93 %
15ꢀ 100 min/
96 %
[34]
[35]
11.
Cu(II)–TD@nSiO2
EtOAc, 50 ◦C.
Ethanol/air/
12.
GLR–G2–Cu polymer
1 h/95 %
[36]
30 ◦
C
Appendix A. Supplementary data
13.
14.
15.
16.
GO-VB1 (30 mg)
Ethanol/rt
30 min/95 %
45 min/96 %
3 h/97 %
[37]
[16]
[38]
[39]
CuMVs (2 ppm, 20 mL),
MTF-1E (20 mg)
Water/30 ◦
C
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.apcata.2021.118005.
Water/ 40 ◦
C
Fe3O4@SiO2@(NH4)6Mo7O24
(0.22 g)
Ethanol/H2O2
(0.2 mL)/rt
Ethanol/rt
30 min/95 %
17.
CFNP@SO3H (20 mg)
10ꢀ 25 min/
PW
98 %
8

P. Yadav et al.
Applied Catalysis A, General 612 (2021) 118005
[19] W.J. Stark, Angew. Chem. Int. Ed 50 (6) (2011) 1242–1258.
References
¨
[20] A. Schatz, O. Reiser, W.J. Stark, Chem. Eur. J. 16 (30) (2010) 8950–8967.
[21] H.M. Tedjieukeng, P.K. Tsobnang, R.L. Fomekong, E.P. Etape, P.A. Joy, A. Delcorte,
J.N. Lambi, RSC Adv. 8 (67) (2018) 38621–38630.
[1] B. Agrahari, S. Layek, R. Ganguly, N. Dege, D.D. Pathak, J. Organomet. Chem. 890
(2019) 13–20.
[22] R.N. Grass, E.K. Athanassiou, W.J. Stark, Angew. Chem. Int. Ed. 46 (26) (2007)
4909–4912.
[2] B. Fang, C.H. Zhou, X.C. Rao, Eur. J. Med. Chem. 45 (9) (2010) 4388–4398.
[3] J.L. Adams, J.C. Boehm, T.F. Gallagher, S. Kassis, E.F. Webb, R. Hall, M. Sorenson,
R. Garigipati, D.E. Griswold, J.C. Lee, Bioorg. Med. Chem. Lett. 11 (21) (2001)
2867–2870.
[23] B. Majumdar, S. Mandani, T. Bhattacharya, D. Sarma, T.K. Sarma, J. Org. Chem. 82
(4) (2017) 2097–2106.
[24] S. Sheikh, M.A. Nasseri, M. Chahkandi, A. Allahresani, O. Reiser, J. Hazard. Mater.
(2020), 122985.
[4] P.S. Hameed, A. Raichurkar, P. Madhavapeddi, S. Menasinakai, S. Sharma, P. Kaur,
R. Nandishaiah, V. Panduga, J. Reddy, V.K. Sambandamurthy, D. Sriram, ACS Med.
Chem. Lett. 5 (7) (2014) 820–825.
[25] J.K. Yadav, P. Yadav, S.K. Awasthi, A. Agarwal, RSC Adv. 10 (2020) 41229.
[26] R.K. Sharma, S. Yadav, S. Sharma, S. Dutta, A. Sharma, ACS Omega 3 (11) (2018)
15100–15111.
[5] A. Husain, M. Rashid, R. Mishra, S. Parveen, D.S. Shin, D. Kumar, Bioorg. Med.
Chem. Lett. 22 (17) (2012) 5438–5444.
[27] P. Singh, P. Yadav, A. Mishra, S.K. Awasthi, ACS Omega 5 (8) (2020) 4223–4232.
[28] S. Ali, M.H. Asad, S. Maity, W. Zada, A.A. Rizvanov, J. Iqbal, B. Babak, I. Hussain,
Bioorg. Chem. 88 (2019), 102936.
[6] A.T. Mavrova, K.K. Anichina, D.I. Vuchev, J.A. Tsenov, P.S. Denkova, M.
S. Kondeva, M.K. Micheva, Eur. J. Med. Chem. 41 (12) (2006) 1412–1420.
[7] Y. Kohara, K. Kubo, E. Imamiya, T. Wada, Y. Inada, T. Naka, J. Med. Chem. 39 (26)
(1996) 5228–5235.
[29] K.B. Dhopte, R.S. Zambare, A.V. Patwardhan, P.R. Nemade, RSC Adv. 6 (10) (2016)
8164–8172.
[8] P.S. Charifson, A.L. Grillot, T.H. Grossman, J.D. Parsons, M. Badia, S. Bellon, D.
D. Deininger, J.E. Drumm, C.H. Gross, A. LeTiran, Y. Liao, J. Med. Chem. 51 (17)
(2008) 5243–5263.
[30] D.Q. Dong, W.J. Chen, Y. Yang, X. Gao, Z.L. Wang, ChemistrySelect 4 (8) (2019)
2480–2483.
[31] A. Farrokhi, M. Jafarpour, F. Feizpour, ChemistrySelect 3 (4) (2018) 1234–1241.
[32] A. Khoshyan, M. Pourtahmasb, F. Feizpour, M. Jafarpour, A. Rezaeifard, Appl.
Organomet. Chem. 33 (2) (2019), e4638, https://doi.org/10.1002/aoc.4638).
[33] X. Li, R. Hu, Y. Tong, Q. Pan, D. Miao, S. Han, Tetrahedron Lett. 57 (41) (2016)
4645–4649.
[9] A. Kasprzak, M. Bystrzejewski, M. Poplawska, Dalton Trans. 47 (18) (2018)
6314–6322.
[10] R.S. Keri, A. Hiremathad, S. Budagumpi, B.M. Nagaraja, Chem. Biol. Drug Des. 86
(1) (2015) 19–65.
[11] N. Singh, D.O. Jang, Org. Lett. 9 (10) (2007) 1991–1994.
[12] R. Kakkar, R. Garg, J. Mol. Struct. Theochem. 584 (1-3) (2002) 37–44.
[13] A. Mobinikhaledi, H. Moghanian, S.M. Ghazvini, A. Dalvand, J. Porous Mater. 25
(4) (2018) 1123–1134.
[34] G.M. Martins, T. Puccinelli, R.A. Gariani, F.R. Xavier, C.C. Silveira, S.R. Mendes,
Tetrahedron Lett. 58 (20) (2017) 1969–1972.
[35] M. Zakeri, M. Moghadam, V. Mirkhani, S. Tangestaninejad, I.M. Baltork,
Z. Pahlevanneshan, Appl. Organomet. Chem. 32 (1) (2018), e3937, https://doi.
org/10.1002/aoc.3937.
[14] A. Arya, V. Mishra, T.S. Chundawat, Chem. Data Collect. 20 (2019), 100190.
[15] S. Bonacci, G. Iriti, S. Mancuso, P. Novelli, R. Paonessa, S. Tallarico, M. Nardi,
Catalysts 10 (8) (2020) 845.
[36] G. Smitha, K. Sreekumar, RSC Adv. 6 (22) (2016) 18141–18155.
[37] H. Ghafuri, N. Joorabchi, A. Emami, H.R.E. Zand, Ind. Eng. Chem. Res. 56 (22)
(2017) 6462–6467.
[16] N. Kaur, S. Kaur, G. Kaur, A. Bhalla, S. Srinivasan, G.R. Chaudhary, J. Mat. Chem. A
7 (29) (2019) 17306–17314.
[38] S. Roy, B. Banerjee, N. Salam, A. Bhaumik, S.M. Islam, ChemCatChem 7 (17)
(2015) 2689–2697.
¨
[17] A. Schatz, R.N. Grass, W.J. Stark, O. Reiser, Chem. Eur. J. 14 (27) (2008)
8262–8266.
[39] G. Bai, X. Lan, X. Liu, C. Liu, L. Shi, Q. Chen, G. Chen, Green Chem. 16 (6) (2014)
3160–3168.
¨
[18] S. Wittmann, A. Schatz, R.N. Grass, W.J. Stark, O. Reiser, Angew. Chem. Int. Ed. 49
(10) (2010) 1867–1870.
9