Metallovesicles as smart nanoreactors for green catalytic synthesis of benzimidazole derivatives in water

Article abstract of DOI:10.1039/c9ta05441c

Metallovesicles are an emerging class of soft nanomaterials where spherical bilayer membranes, resulting from self-aggregation of amphiphilic metal complexes, amalgamate the advantages of metal specific catalytic properties and small hydrophobic cavities

Full text of DOI:10.1039/c9ta05441c

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ISSN 2050-7488
PAPER
Kun Chang, Zhaorong Chang et al.
Bubble-template-assisted synthesis of hollow fullerene-like
MoS nanocages as a lithium ion battery anode material
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Metallovesicles as smart nanoreactors for green catalytic synthesis of benzimidazole
derivatives in water
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Navneet Kaur, Simranpreet Kaur, Gurpreet Kaur, Aman Bhalla, Sesha Srinivasan and
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Ganga Ram Chaudhary
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aDepartment of Chemistry & Centre for Advanced Studies in Chemistry, Panjab University,
Chandigarh-160014, India
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Florida Polytechnic University, Lakeland-33805, Florida, USA
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*Corresponding author.
Tel.: +91-172 2534406; Fax: +91-172-2545074
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E-mail address: grc22@pu.ac.in (Ganga Ram Chaudhary)
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Metallovesicles are an emerging class of soft nanomaterials where spherical bilayer membranes,
resulting from self-aggregation of amphiphilic metal complexes, amalgamate the advantages of
metal specific catalytic properties and small hydrophobic cavities serving as nanoreactors. The
confinement of substrates in these vesicle bilayers, on account of hydrophobic interactions in
aqueous media, encourage their application in catalysis, particularly, where preclusion of organic
solvents is of prime concern without compromising desired reaction rates and product yields. In
the present work, novel amphiphilc metallosurfactant complex [Cu(C H NH ) ]Cl has been
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self-assembled to achieve spherical bilayer structures known as copper metallovesicles
(CuMVs). DLS, TEM and FESEM analyses revealed the formation of spherical multivesicular
vesicles in the size range 160-200 nm. The multivesicular structure of CuMVs was further
supported by small angle x-ray scattering (SAXS) results. The as-synthesized CuMVs were
further assessed for their potential as aqueous catalytic system for the synthesis of important
therapeutic agents, benzimidazoles. The co-existence of hydrophobic reactants inside the metal-
adorned vesicle bilayers, affords high product yield in short times. Facile synthesis of
metallosurfactants, self-assembly to metallovesicles, aqueous reaction media, low metal
concentration, low E-factor values, stability and recyclability of metallovesicles are the features
that establish metallovesicular catalysis as a promising multifaceted approach for greener
catalysis of benzimidazole synthesis and many other significant synthetic reactions.
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Keywords: Metallovesicles, nanoreactor, metallosurfactant, benzimidazoles, green chemistry,
catalysis, water
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1. Introduction
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In recent years, the scientific community has become more sensitive towards environmental
issues and has worked illustriously in developing such protocols for synthesis of organic
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molecules, which not only, are environment friendly but sustainable as well. All the catalytic
approaches, whether they involve homogeneous or heterogeneous catalysts, are critically
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examined on the scale of green chemistry. Besides the cost and energy factor, the major factor
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that decides the green nature of a catalytic protocol is the choice of reaction media. Many
organic syntheses that involve harmful organic solvents as reaction media are high on E-factor
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value which is a prime concern in developing eco-friendly and sustainable protocols. Water, for
its inexpensive, non-toxic and non-flammable nature, has intrigued the scientists to develop
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methods that favor organic syntheses of molecules in water. While heterogeneous catalysis in
water requires high temperatures (preferably microwaves), the homogeneous catalysis in
presence of water poses difficulties in separation of products and even contamination of water
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for reuse. The challenge of combining the better selectivity of homogeneous catalysis with the
recoverability and reusability factor of heterogeneous catalysis puts forward the need of
developing innovative and smart materials that smartly address the demands of green catalysis.
Nanoreactors, comprising of the non-covalent self-assemblies of amphiphilic molecules, have
emerged as excellent alternatives to combine the features of homogeneous and heterogeneous
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catalysis in one-pot. The amphiphilic nature of these self assemblies resolve the solubility issues
of substrates in water, which are held together in hydrophobic pockets of these self-assembled
nanoreactors. The compartmentalization of substrates results in their increased proximity and
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concentration around active catalytic sites. In literature, a vast variety of amphiphilic aggregates
like micelles, vesicles, microemulsions, liposomes, polymerosomes etc. of suitable morphology
are known to enhance the reaction rates of many organic reactions.9-13 Vesicles, for instance,
have better catalytic performance in comparison to micelles and other aggregates14-16 because of
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the following four factors (i) they possess chemical aspects of biological membranes and show
tremendous selectivity (ii) they increase the proximity between the reagents by decreasing the
effective volume where the reaction takes place (iii) their structural complexity provides
necessary stearic-hindrance to avoid side reactions (iv) they provide reaction centers with
different polarity in comparison to the bulk solvent. Depending upon reaction requirements, the
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fourth factor can be altered by incorporation of a metal ion into the vesicular structure. The
metallovesicles, formed as a result of functionalization of traditional vesicles with suitable metal
ions, are adorned with notable catalytic properties.18-19 Though there are numerous applications
of vesicular systems in drug delivery, model protocells, vaccination and reaction promoters20-24
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the metallovesicular systems are very less explored for their potential as efficient catalytic
systems.
The aim of the present work is two-fold; one, to fabricate metallovesicles (CuMVs) from
amphiphilic metallosurfacatnt complex, bisdodecylaminecopper(II)chloride and assess their
structural details. And two, to efficiently use the as-fabricated CuMVs, as catalyst, in synthesis
of benzimidazole derivatives in milder reaction conditions with water as solvent. Benzimidazole
and its derivatives are important building blocks of pharmaceutical industries owing to their
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various biological activities such as antiarrhythmic, antiulcer, ionotropic, antihelmintic,
anticancer29 and antimicrobial activities.30 Furthermore, these compounds have significant
industrial applications in UVB filters, optical devices, paints, and fuel cell membranes.31-34 Many
reports are available in literature to synthesize benzimidazoles by the condensation of
arylaldehydes with ortho-phenylenediamines using variety of homogeneous and heterogeneous
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catalysts, for e.g. acetic acid, trimethylsilyl chloride, oxone, sulphamic acid, PhI(OAc) ,
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KHSO4,40 K PO , Amberlite,42 L-proline,43 CoCl2,44 PTSA,45 metal triflates,46 heteropoly
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acids, solid support catalysts and ionic liquids etc. Unfortunately, many of these methods
suffer from drawbacks such as environmentally hazardous solvents/reagents, drastic reaction
conditions, low yields, tedious workup procedures, low atom economy and various side products.
Nanoparticles have also been utilized as heterogeneous catalysts in this synthesis but most of the
high-performing nanoparticles catalysts include expensive transition metals, hazardous oxidants
generating toxic by-products. 50-56 As a consequence, the introduction of an efficient and mild
method is still needed to overcome these limitations. The present catalytic system, comprising of
CuMVs, offers a room temperature synthesis of 2-aryl-1H-benzimidazole derivatives at low
metal concentration in aqueous media which is economic, environmentally benign, recyclable
and energy efficient. The intriguing results obtained with CuMVs in the present synthetic
reaction with low E-factor values, expand their scope as catalysts in other reactions as well as
gives direction in designing similar catalytic structures with different functionalities.
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2. Experimental
2.1. Materials
Copper(II) chloride (99%), dodecylamine (98.6%), o-phenylenediamine (99%), cholesterol
(99%) and DMSO-d6 were purchased from Sigma Aldrich. Chloroform and diethyl ether were
purchased from Fischer Scientific. O-phenylenediamine (99%) was purchased from Sigma
Aldrich and various aromatic aldehydes (>98%) were purchased from Himedia. All the
chemicals were used as received without any further purification. Polycarbonate microfilters
(0.25 micron pore size) were purchased from Millipore.
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2.2.
Designing the catalyst
2.2.1. Fabrication of copper metallovesicles (CuMVs)
We are hereby proposing a catalyst design which adheres to all the prerequisites for the synthesis
of benzimidazole derivatives. In our previous report, we have described the synthesis of a
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metallosurfactant complex, bisdodecylaminecopper(II) chloride [Cu(C H NH ) ]Cl which is
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used as precursor for the fabrication of CuMVs in present report.
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The CuMVs were prepared by employing conventional chloroform film method. Equimolar
amounts of [Cu(C H NH ) ]Cl (5 mmol) and cholesterol (5 mmol) were dissolved in CHCl
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(20 mL). The solution was stirred at 333 K in a round bottom flask for 30 minutes followed by
slow evaporation of CHCl under reduced pressure. The resulting thin film on the surface of
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round bottom flask was dried in vacuum desiccator at room temperature for 24 h and further
hydrated with deionized water (100 ml). The obtained solution was repeatedly sonicated,
subjected to vortex shaker for about 4 h and obtruded through polycarbonate microfilters (0.25
micron pore size) for at least 10 times which resulted in uniform particle size distribution as
monitored by Dynamic Light Scattering (DLS). Different volumes of this solution were further
used for catalytic synthesis of benzimidazole derivatives.
2.2.2. Characterization techniques
The formation of CuMVs was confirmed by different characterization techniques such as DLS,
Atomic Force Microscopy (AFM), Confocal Laser Scanning Microscopy (CLSM), Transmission
Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM) and
Small Angle X-ray Scattering (SAXS). Size measurements of CuMVs were done by DLS
experiments performed on ALV-5000 with Nd:YAG laser (wavelength 532 nm) at room
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temperature. For TEM analysis, samples of CuMVs were dispersed on a carbon coated copper
grid and air dried grid was analyzed using Hitachi H 7500 instrument operated at 80-110 kV. For
FESEM images were taken with Hitachi (SU8010) at various operating voltages (3-20 kV). AFM
images were obtained on Nanoscope “V-multimode 8”. The instrument was operated in the
contact mode with an operating frequency of 312.13 kHz. Confocal Laser Scanning Microscope
(CLSM) images were taken on Nikon Eclipse Ti(C2Si) inverted microscope (100x objective)
with attached Nikon camera. Nikon ECLIPSE E100 with attached camera was used to obtain
optical micrographs of CuMVs. SAXS studies were performed on SAXSpace by Anton Paar
operated on line collimation mode at 40 kV. Quartz capillary liquid cell of 1 mm diameter was
used to hold the sample. The scattering pattern was recorded using CCD detector having
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scattering vector q ranges from 0.01 nm to 8 nm . All the measured intensity was normalised
and the background scattering contributions from capillary / solvent were corrected. The data
were evaluated with General Inverse Fourier Transformation (GIFT) software. The phase
transition temperature of metallosurfacatnt complex was found through Differential Scanning
Calorimetry (DSC), performed on DSC-Q20 (TA instrument, USA) at scanning range of 10 ° C
/min. ICP-MS analyses were done on ICP-MS Agilent 7800 to determine concentration of Cu in
metallovesicle solution.
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2.3. Catalytic synthesis of 2-aryl-1H-benzimidazoles
2.3.1. General procedure: A mixture of o-phenylenediamine (1 mmol) and aromatic
aldehyde (1 mmol) was added to a round bottom flask containing CuMVs solution (20 ml,
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containing 2 ppm Cu ) (scheme 1). The mixture was stirred well at 303 K, and the progress of
the reaction was monitored by thin layer chromatography at regular time intervals. As the
reaction proceeded to completion, the precipitation of product took place. After completion, the
reaction mixture was filtered to separate the product and obtained solid was recrystallized in
ethanol. Benzimidazole derivatives, which could not be crystallized, were purified with the help
of column chromatography.
NH2
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NH2
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H
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Scheme 1 Synthesis of 2-substituted benzimidazoles
R = H, 2-OCH , 4-OCH , 4-NO , 3- NO , 4-Cl, 4-Br, 4-CN, 4-CH
3 3 2 2 3
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2.3.2. Characterization of products: The identification of all the synthesized
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benzimidazole derivatives was done through H NMR using CDCl as a solvent. The physical
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and spectral data of all the products (Entries 1a-1i, Table 1) is given in supplementary
information (section S1, ESI).
2.3.3. Recycling the catalyst: The CuMVs were collected as filterate after filtration of
reaction mixture and were purified with diethyl to extract traces of unreacted substrates (if any).
The as-collected free aqueous CuMVs solution was used in next catalytic cycles to check their
recycling efficiency.
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3. Results and Discussion
This article engulfs a green and highly efficient catalytic synthesis of benzimidazole derivatives
using specially designed aqueous CuMVs. Recyclable CuMVs have a dual role to play i.e. apart
from behaving as nano-vessels to accommodate reactants within them and increase their physical
proximity; they also provide acidic sites integrated within the aggregated structure that
expeditiously catalyzes the model reaction.
An amphiphilic metallosurfactant complex of copper equipped with two long
hydrocarbon chains viz [Cu(C H NH ) ]Cl was synthesized and further used for the
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preparation of CuMVs using film hydration method. The thin film as described in section 2.2.1
consists of sediments of multiple bilayers which were sonicated and mechanically vortexed with
deionised water at a temperature above the phase transition temperature (333 K) of
metallosurfactant complex (illustrated by DSC, Figure S1, ESI). This resulted in swelling and
folding of these lamellar bilayer structures into spherical CuMVs. The addition of equimolar
amounts of cholesterol to metallosurfactant complex was done to to meliorate rigidity and
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stability of CuMVs. The notably polydisperse CuMVs were repeatedly extruded (at least 10
times) through polycarbonte microfilters resulting in monodisperse CuMVs as monitored by
DLS.60 DLS analyses of CuMVs before and after extrusion are given in (Figure S2, ESI)
respectively. The polydispersity index of CuMVs was reduced from 0.367 to 0.132 after
extrusion. The average size of extruded CuMVs was found to be 220 nm. It is to be noted that
amount of water used for hydration process has no effect on CuMVs’ morphology. However, it
results in the variation of concentration of resulting CuMVs in solution.
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Morphological details of CuMVs were obtained by different microscopic techniques.
Preliminary structural examination of CuMVs was done with conventional light microscope that
showed spherical structures (Figure S3(a), ESI). Further detailed examination of size,
morphology and topography of the CuMVs was carried out using TEM, CLSM, FESEM and
AFM techniques. TEM, CLSM and FESEM analysis gave a fairer insight into the size,
morphology and lamellarity whereas AFM studies showed topographical analysis of the prepared
CuMVs. TEM image (Figure 1(a)) shows the formation of multivesicular metallovesicles (large
number of small vesicles inside a giant vesicle) in the size range 160-200 nm. Inset of Figure
1(a) shows high resolution TEM image of a multivesicular vesicle (180 nm). The spherical shape
of CuMVs is further confirmed through CLSM images (Figure 1(b)). Also, the FESEM results
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affirm with those of TEM showing spherical shaped structures (Figure S3(b)). AFM images
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show height and phase topographies of CuMVs (Figure S3(c) and S3(d), respectively). Color
contrast in height images reveals the average particle size of CuMVs in the range of 180-200 nm
however vesicles are found to be vertically compressed due to high local force applied by the tip
of the cantilever. Colour contrast in phase image shows distinct phase boundaries as we move
from one metallovesicle to other, showing segregated distribution of CuMVs. Careful analysis of
the phase images shows colour contrast within the same vesicle illustrating the presence of
different phases in accordance with multivesicular topography.
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Figure 1 Structural investigation of CuMVs showing (a) TEM micrograph, inset: single
multivesicular vesicle (b) CLSM image.
Further structural investigation of CuMVs was done using SAXS. Figure 2(a) shows
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experimental SAXS scattering profile of CuMVs in which scattering intensities I(q) are plotted
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as a function of scattering vector q, which is defined as 4πsinθ/λ; where θ is half the scattering
angle and λ is wavelength of X-rays. The absence of distinct diffraction maxima in SAXS profile
suggested the lack of periodicity in the structures.61 This was indicative of multivesicular
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structure of CuMvs consisting of non-concentric bilayers. Also, the power law (q ) of scattering
curve in line collimation mode suggested vesicular structures.61-63 The interpretation of scattering
curve in real space was done using General Inverse Fourier Transformation (GIFT) which
generated Pair Distance Distribution Function (PDDF), P(r). Figure 2(b) and (c) show the
approximated SAXS scattering data fit with experimental data after carrying out indirect fourier
transformation and the corresponding PDDF, respectively. It can be seen that the data fits well
with experimental data and the PDDF curve i.e. P(r) v/s r shows asymmetry with alternate signs
of distribution function. Since P(r) is calculated by weighting two electron density values
connected by distance r, the asymmetry in signs of P(r) points towards inhomogenous interior of
CuMVs.
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Figure 2(a) SAXS scattering profile of CuMVs (b) approximated scattering curve (red)
after carrying out Indirect Fourier Transformation and (c) the corresponding PDDF.
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3.1. Catalytic synthesis of 2-aryl-1H-benzimidazoles using CuMVs
The CuMVs were tested for their catalytic efficiency in synthesis of various benzimidazole
derivatives (Entries 1a-1i, Table 1). The optimum reaction conditions were obtained by choosing
a model reaction between o-phenylenediamine and 4-chlorobenzaldehyde was chosen (scheme 2)
to obtain the optimum reaction conditions by varying different reaction parameters like catalyst
dose and temperature. In all the experiments, the progress of the reaction was monitored by thin
layer chromatography and % product yield were noted.
NH2
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Scheme 2 Model reaction between o-phenylenediamine and 4-chlorobenzaldehyde
Initially, a blank experiment was run where the model reaction was performed in the absence of
CuMVs. The reaction did not show any progress even after 4 h suggesting the need of catalyst
for successful conversion of reactants to product.
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In order to optimize the catalyst dose for the reaction, the CuMVs solution was initially assessed
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for concentration of catalytically active sites (Cu ) using ICP-MS analysis that suggested it to be
2 ppm. The model reaction was then carried out with different volumes of CuMVs solution.
Figure 3(a) summarizes the time for reaction completion and isolated product yield in each case.
An increase in the volume of CuMVs solution led to faster completion of reaction with increased
product yield.
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Figure 3 (a) Effect of catalytic dose (b) variation of product yield with reaction temperature
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Reaction conditions (a): o-phenylenediamine (1 mmol), 4-chlorobenzaldehyde (1 mmol), CuMVs (2 ppm), 303 K (b) 20 ml.
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The results could be understood in terms of increase in number of catalytically active Cu sites.
Increasing the volume of solution ensured more number of CuMVs and hence faster reactions
with better yields. The constant results beyond 20 ml of catalyst volume suggest the complete
encapsulation of reactants in the CuMVs. Introduction of anymore amount of CuMVs did not
affect the reaction rate as there was no further encapsulation of reactants in newly introduced
CuMVs. The catalytic reaction was also performed at higher temperatures to understand the
effect of temperature on the reaction performance. It was found that increasing the reaction
temperature had negligible effect on product yield (Figure 3(b)). Based on these results, the
optimum reaction temperature for the reaction was fixed to be 303 K.
3.2.
Substrate scope
The designed catalytic system has wide applicability as it covers a large number of substrates
for the synthesis of various benzimidazole derivatives. The reaction was performed with
different aromatic aldehydes carrying different substituents and good to excellent product yields
were obtained in all the cases (Table 1). The reaction times are greatly influenced by the electron
releasing or withdrawing nature of substituents attached to the aromatic ring. As expected from
the first step of mechanism which is nucleophillic attack of o-phenylenediamine on aromatic
aldehyde, electron withdrawing groups increase the electrophilicity of carbonyl carbon favouring
the nucleophillic attack. This accounts for the lower reaction times for electron withdrawing
groups as compared to electron releasing groups. However, for same group longer reaction times
were observed for the ortho and meta substitutions due to stearic reasons.
3.3.
E-factor calculations
The environmental impact of the catalytic protocol was assessed through E-factor calculations
which measures the amount of waste generated during a synthetic process. The calculations were
done using Eq. 1 as follows:
3
06
E-factor =
Eq. 1
3
3
3
3
3
07
08
09
10
11
It is to be noted that since the CuMVs were recovered during the process for further usage, mass
of CuMVs have been omitted from the E-factor calculations. The values of E-factor have been
calculated for synthesis of all the benzimidazole derivatives and are given in Table 1. It can be
seen from Table 1 that E-factor values are very small ranging between 0.14 and 0.21 which
advocates the green nature of the protocol. This is attributed to minimum waste generation
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during the process which occurs in water as reaction medium in presence of highly active
recyclable CuMVs.
Table 1 Effect of substituent (on aromatic aldehyde) on reaction rate
Aromatic
aldehyde
CHO
Time
(mins)
Yield
(%)
Entry Diamine
Product
E-factor
*
NH2
N
1
a
70
85
94
90
0.175
N
H
NH2
NH2
H CO
CHO
3
N
OCH3
1
b
0.212
0.173
NH2
N
H
CHO
N
NH2
NH2
OCH3
1
c
80
45
93
95
N
H
OCH3
CHO
N
NH2
NH2
NO2
1
d
0.142
N
H
NO2
NO2
CHO
NH2
N
1
e
50
60
75
60
93
95
95
96
0.166
0.148
0.130
0.138
N
NH2
H
NO2
CHO
NH2
NH2
N
1
f
Cl
N
H
Cl
CHO
NH2
NH2
N
1
g
Br
N
H
Br
CHO
NH2
N
1
h
CN
N
NH2
H
CN
1
2

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CHO
CH3
N
NH2
NH2
CH3
1
i
80
91
0.206
N
H
3
3
15
16
Reaction conditions: o-phenylenediamine (1 mmol), aromatic aldehyde (1 mmol), CuMVs (2 ppm, 20 ml), 303 K
*
Isolated yield
3
3
3
3
3
3
17
18
19
20
21
22
3.4.
Mechanistic aspects of catalysis with CuMVs
2
+
The CuMVs act as small nanoreactors bearing catalytically active Cu sites. The hydrophobic
pockets inside the multivesicular structure of CuMVs encapsulate the substrates and increase
their concentration at catalytically active Cu2+ sites resulting in faster catalysis. This
encapsulation of substrates in hydrophobic regions is evidenced through CLSM image of
CuMVs encapsulated with reactant (4-bromobenzaldehyde) (Figure 4).
3
3
23
24
Figure 4 CLSM micrograph of CuMVs loaded with 4-bromobenzaldehyde.
3
3
3
3
3
3
3
25
26
27
28
29
30
31
The proposed mechanism for the reaction taking place inside the CuMVs is depicted in Scheme
2
+
S1 (ESI). The Cu sites in the CuMVs activate the carbonyl carbon of the aromatic aldehyde for
nucleophilic attack by –NH group of o-phenylenediamine. The resulting imine is further
2
attacked by second –NH to form dihydroimidazole followed by aromatization in presence of air
2
to give 2-aryl-1H-benzimidazoles as product.
3.5.
Reusability Tests
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33
34
35
36
The developed catalytic system was assessed for its recycling efficiency. Firstly, the CuMVs
st
solution recycled after 1 reaction cycle was investigated for structural intergrity of CuMVs
using FESEM and Light microscope (Figure 5). It can be seen from FESEM image (Figure 4(a))
and optical micrographs (Figure 5(b)) that the recycled CuMVs maintained their structural
integrity.
3
37
st
3
3
38
39
Figure 5 (a) FESEM image and (b) optical micrograph of CuMVs recovered after 1 cycle
of catalytic reaction.
3
3
3
3
40
41
42
43
The recycled CuMVs solution was subjected to further catalytic cycles and the reaction
performance was noted in each case. It was found that the CuMVs maintained their catalytic
performance for up to 6 reaction cycles (Figure 6). The performance is attributed to mechanical
strength and stability of metallovesicular structures.
3
3
44
45
Figure 6 Recycling efficiency of CuMVs
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47
The decline in the performance of the catalytic system can be explained on the basis of rupture of
th
metallovesicle structure on repeated use beyond 6 cycle (Figure S4, ESI).
3
3
3
3
3
3
3
3
3
3
3
3
3
48
49
50
51
52
53
54
55
56
57
58
59
60
4. Advantage over other catalytic systems and future prospects
The synthesis of 2-aryl-1H-benzimidazole derivatives has been achieved with a number of
catalysts in literature. The reaction conditions and their catalytic performance are tabulated in
Table 2. It can be seen that most of the catalysts, apart from their own toxic nature, require high
temperatures, toxic solvents as reaction medium and tedious work-up procedures to separate the
5
0
products. The transition metal oxide nanoparticles (In O ), though prove to be an efficient
2
3
alternative in terms of their activity and recoverability, compromise with the cost factor which
cannot be ignored for the implementation of the protocol on large scale. The present system is
found to qualify all the significant conditions of an efficient catalytic system like high activity,
environment benignity, cost effectiveness, recyclability and ease of product separation. The
catalytic systems consisting of metallovesicles have a promising scope in future of metal-assisted
catalysis of organic reactions and transformations which, otherwise, require traditional organic
solvents and expensive metal catalysts.
3
3
61
62
Table 2 Comparison of catalytic performance of present catalytic system with literature reports
for the synthesis of 2-sustituted benzimidazoles.
S. No.
Catalyst
Catalyst dose
Time/ yield (%)
1 h/ 92 %
Solvent/
Temperature
Ref.
[64]
[65]
[66]
[67]
[68]
[69]
1
2
3
4
5
6
.
.
.
.
.
.
VOSO4
3 mol %
EtOH/ rt
TiCl OTf
10 mol %
30 mol %
4 equivalent
10 mol %
10 mol %
50 mins/ 86 %
1.5-2 h/93 %
2 h/ 95 %
EtOH/ rt
3
Ce(NO ) .6H O
DMF/ 80°C
DMF/120°C
EtOH/ rt
3
3
2
PhSiH3
Co(OH)2
4-7 h/ 82-96 %
1.8 h/ 93 %
ClSO H
2-propanol/ rt
3
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7
8
9
.
.
.
CuFe O NPs
20 mol%
20 mg
24 h/89%
toluene/O2
H O/O
[51]
[52]
[53]
[54]
2
4
Mesoporous TiO2-
Fe O
3h/97%
1h/78%
2
2
2
3
Pt/TiO2
1 mol%
220 mg
mesitylene
EtOH/H O
1
0.
Fe O -SiO -
0.5 h/90%
3
4
2
2
2
(
NH ) Mo O
4 6 7 24
nanocomposite
1
1
1
1.
2.
3.
α –MoO nanobelts
2 mol%
10 mol%
0.03 mol%
0.5 h/93%
1 h/96%
1 h/96%
t-BuOOH
CH CN/O
[55]
[56]
3
CuI Nps
CuMVs
3
2
H O
2
Present
work
3
3
3
63
64
65
5. Conclusions and Outlook
3
3
3
3
3
3
3
3
3
3
3
3
3
3
66
67
68
69
70
71
72
73
74
75
76
77
78
79
In conclusion, novel metallovesicles, CuMVs have been fabricated using metallosurfactant
complex, bisdodecylaminecopper(II)chloride. The as-fabricated metallovesicles have been
employed as nanoreactors for the catalytic synthesis of 2-aryl-1H-benzimidazole. The successful
condensation of o-phenylenediamine with aromatic aldehydes in aqueous metallovesicles
solutions under mild reaction conditions to give excellent product yields, establish the claim of
these novel metallovesicles as small nanoreactors possessing active catalytic sites. The notable
catalytic activity, harmless aqueous reaction medium, ambient reaction conditions promote the
as-developed catalytic approach as effective and greener approach for benzimidazole synthesis.
The strength and stability of metallovesicular structures impart yet another attractive feature to
the catalytic approach in the form of recyclability. Effective catalytic action followed by facile
recovery of metallovesicles enables them to be reused in further reaction cycles. The efficiency
of CuMVs as catalysts in the present protocol opens up the way to diverse applications of these
materials in the field of organic synthesis which requires a dire need to shift to efficient, greener
and sustainable catalytic approaches.
3
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Conflicts of interest
Authors declare no conflicts of interest.
3
3
3
3
3
3
83
84
85
86
87
88
Acknowledgements
Ganga Ram Chaudhary and Sesha Srinivasan would like to acknowledge the support of UGC,
st
India under INDO-US 21 Century Knowledge Initiative project [F.No. 194-2/2016 (IC)].
Navneet Kaur is thankful to UGC for Senior Research Fellowship. Gurpreet Kaur acknowledges
DST, India for Inspire Faculty award (IFA-12-CH-41). All the authors acknowledge the support
of DST PURSE II grant for this work.
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
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90
91
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94
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01
02
03
04
05
06
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08
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Graphical Abstract
Green catalytic synthesis of benzimidazoles using Cu metallovesicles as nanoreactors