Synthesis of quinoxaline, benzimidazole and pyrazole derivatives under the catalytic influence?of biosurfactant-stabilized iron nanoparticles in water

Article abstract of DOI:10.1007/s11164-020-04240-6

Abstract: We have reported the synthesis, characterization, and catalytic applications of amorphous iron nanoparticles (FeNPs) using aqueous leaves extract of renewable natural resource Boswellia serrata plant. Synthesized FeNPs were stabilized in situ by the addition of aqueous pod extracts of Acacia concinna as a biosurfactant (pH 3.11). The structural investigation of biosynthesized nanoparticles was performed using UV–visible spectroscopy, X-ray diffraction analysis, selected area electron diffraction, energy-dispersive X-ray spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and BET analysis. The FeNPs were amorphous in nature with average particle size ~ 19?nm and successfully employed as heterogeneous catalyst for the synthesis of quinoxaline, benzimidazole, and pyrazole derivatives in aqueous medium at ambient conditions. The FeNPs could be recycled up to five times with modest change in the catalytic activity. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-020-04240-6

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04240-6
Synthesis of quinoxaline, benzimidazole and pyrazole
derivatives under the catalytic infuence of
biosurfactant‑stabilized iron nanoparticles in water
Satyanarayan M. Arde1 · Audumbar D. Patil1,2 · Ananda H. Mane3 ·
Prabha R. Salokhe4 · Rajashri S. Salunkhe1
Received: 17 February 2020 / Accepted: 12 August 2020
© Springer Nature B.V. 2020
Abstract
We have reported the synthesis, characterization, and catalytic applications of amor-
phous iron nanoparticles (FeNPs) using aqueous leaves extract of renewable natural
resource Boswellia serrata plant. Synthesized FeNPs were stabilized in situ by the
addition of aqueous pod extracts of Acacia concinna as a biosurfactant (pH 3.11).
The structural investigation of biosynthesized nanoparticles was performed using
UV–visible spectroscopy, X-ray difraction analysis, selected area electron difrac-
tion, energy-dispersive X-ray spectroscopy, scanning electron microscopy, trans-
mission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric
analysis, and BET analysis. The FeNPs were amorphous in nature with average par-
ticle size ~19 nm and successfully employed as heterogeneous catalyst for the syn-
thesis of quinoxaline, benzimidazole, and pyrazole derivatives in aqueous medium
at ambient conditions. The FeNPs could be recycled up to fve times with modest
change in the catalytic activity.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04240-6) contains supplementary material, which is available to authorized users.
* Rajashri S. Salunkhe
rsschem1@gmail.com
1
Department of Chemistry, Shivaji University, Kolhapur, MS 416004, India
2
Department of Chemistry, School of Science, Sanjay Ghodawat University, Kolhapur, MS, India
3
Department of Chemistry, KIT’s College of Engineering, Kolhapur, MS 416234, India
4
Department of Chemistry, Y. C. Warana Mahavidyalaya, Warananagar, MS 416113, India
Vol.:(0123456789)
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S. M. Arde et al.
Graphic abstract
Keywords Amorphous iron nanoparticles · Bioreduction · Boswellia serrata ·
Stability of FeNPs · Biosurfactant · N-heterocyclic compounds · Aqueous medium
Introduction
The green synthesis of metallic nanoparticles (NPs) has garnered tremendous atten-
tion in the scientifc community, due to the growing environmental contamination
caused by the conventional chemical methods [1]. Usually, NPs have been synthe-
sized using various chemical and physical methods based on the availability and fea-
sibility of protocols to achieve the required applications [2–5]. However, some of
these methods include use of expensive equipment and hazardous chemicals which
have harmful efects with respect to environment and human health. Moreover, dur-
ing the chemical synthesis, the residuals of some toxic chemicals may adsorb on the
surfaces of the NPs, which prevent their application in biomedical equipment [6].
Therefore, there is immense interest in the development of environmentally friendly
and sustainable methods for the preparation of NPs.
From the literature survey, plenty of reports are available on the synthesis of metal
NPs using bacteria, fungi, microorganisms, and plant extract [7–11]. Amid various bio-
genic syntheses of NPs, use of plant extract could be more advantageous as it does not
involve elaborative process and repeated growth of cell culture of microbes and their
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
maintenance [12]. It was already explored that the rate of metal ion reduction by plant
extract is much faster than the microorganism [13]. The biomolecules in plant extract
like proteins, phenols, favonoids, etc. play the crucial role for the reduction of metal
ions [14], but sometimes plant extracts do not produce stable NPs like magnetic NPs
because they have high propensity to aggregate leading to get larger particle size due to
small surface area. To avoid the agglomeration of magnetic NPs, synthetic stabilizing
agents (surfactants) could be used [15], but the green chemistry principles do not allow
the synthetic surfactants as they might not be ecofriendly. To overcome this difculty,
biosurfactants like aqueous extract of Acacia concinna pods play crucial role in the sta-
bilization of magnetic nanoparticles.
Functionalized magnetic NPs have great interest due to their unique properties and
its wide spread applications [16, 17]. It is a renowned material in the feld of catalysis
over the last decade as they have combine interesting reactivity with an easy, economi-
cal and environmentally benign mode of recovery [18]. In particular, zero-valent FeNPs
represent a wide range of peculiar applications in diferent felds such as magnetic reso-
nance imaging [19], Raman scattering and electrocatalysis [20], remediation of aque-
ous metal contaminants [21], potential magnetic carriers [22], declorination [23], imine
synthesis [24], chromium removal [25], etc.
Considering aforementioned discussion and importance of FeNPs, in present work,
we describe a facile and environmentally friendly technique for the preparation of
FeNPs using an aqueous extract of Boswellia sarrata L. leaves as a bioreductant and
Acacia concinna pods as stabilizing agent. Furthermore, biosynthesized FeNPs were
successfully employed as a heterogeneous catalyst in one-pot multicomponent syn-
thesis of quinoxaline benzimidazole and pyrazole derivatives. Quinoxaline, benzimi-
dazole, and pyrazole scafolds containing molecules have considerable biological and
pharmacological properties [26, 27]. The heterocyclic imidazole nucleus is the most
important scafolds due to their medicinal properties [28] and found in a number of
naturally occurring compounds such as histamine, histidine, pilocarpine, allantoin,
and vitamin B12 [29]. In addition, pyrazole moiety is used as a precursor for the syn-
thesis of compounds presenting many applications such as electrolyte additives in
batteries, catalysis, photographic materials, agrochemicals, dyes and as a versatile
compound used in medicine [30]. Nevertheless, in the traditional approaches of qui-
noxaline synthesis using di-carbonyls with the diamine molecules, use of expensive
reactive reagents, poor yields, harsh reaction conditions are the major issues that have
been reported. In continuation of our previous research work [31–35], development of
sustainable methodology for heterocycle synthesis, herein we have reported synthesis
of quinoxaline, benzimidazole, and pyrazole derivatives by using biosurfactant-stabi-
lized FeNPs. Addition of Acacia concinna aqueous pod extract (a stabilizing agent),
afected the stability of FeNPs, and it remained in suspended form for weeks in aque-
ous solution.
1 3

S. M. Arde et al.
Experimental
General information
All reagents were purchased from Sigma-Aldrich and used without further puri-
fcation. All reagents were weighed and handled in the air at room tempera-
ture. Fresh, green, and mature leaves of Boswellia serrata and pods of Acacia
concinna were collected from “Western Hilly Region” of Maharashtra (India),
and the taxonomic identifcation was made in Department of Botany, Shivaji Uni-
versity, Kolhapur (MS, India). The voucher specimen was numbered (SMA 001)
and kept in our research laboratory for further reference. The aqueous extract of
Boswellia sarrata leaves and Acacia concinna pods were freshly prepared using
double distilled water and kept in dark at room temperature for further use. The
UV–visible spectra were recorded over 200–800 nm range with UV-3600 PC
UV–VIS NIR Spectrophotometer (Shimadzu). XRD patterns were recorded on
Bruker AXS model D-8, (10°–70° range, scan rate = 1° min−1) equipped with a
monochromator and Ni-fltered Cu Kα radiation. SEM was performed using a
HITACHI S-4800 instrument to study the morphology of FeNPs. The TEM anal-
ysis was performed on a Jeol model JEM 1200 electron microscope operated at an
accelerating voltage of 120 kV. The EDS was carried out on a DX-700HS spec-
trometer for elemental analysis. XPS data of catalyst were collected on a VG sci-
entifc ESCA-3000 spectrometer using a non-monochromatized Mg K radiation
(1253.6 eV) at a pressure of about 1 × 10−9 Torr (Pass energy of 50 eV, electron
takeof angle 55°). BET surface area of adsorbants was determined by N2 adsorp-
tion–desorption techniques using Micromeritics-2720 (Chemisoft TPx) volumet-
ric instruments. Melting points were determined in an open capillary and were
uncorrected. 1H NMR spectra were recorded at 300 MHz Bruker Avon spectrom-
eter using CDCl3 as solvent and TMS as an internal reference. IR spectra were
recorded on Thermo Scientifc Neconet 6700 FTIR, in the range 4000–400 cm−1.
Mass spectra were performed on an Ultima Global spectrometer with an ESI
source.
General procedure for the synthesis of FeNPs
Diluted aqueous extract of Boswellia sarrata leaves (25 mL) was added drop
wise to 25 mL of ferrous sulfate solution (1 mM) containing 10 mL of Acacia
concinna pod aqueous extract at room temperature with constant stirring for 3 h.
Acacia concinna pod aqueous extract, a natural surfactant, acted as a stabilizing
as well as capping agent and prevented the agglomeration of FeNPs. The color of
FeSO4 aqueous solution gradually changed from light yellow to black indicated
the formation of FeNPs upon addition of an aqueous solution of plant extract (PE)
(Fig. 1). The obtained black solution was centrifuged at 10,000 rpm for 20 min
and then washed with distilled water (3 × 10 mL). The black solid obtained was
dried under vacuum and used for further study.
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
Fig. 1 Preparation of FeNPs by the exposure of FeSO4 aqueous solution with B. serrata aqueous leaves
extract and A. concinna aqueous pod extract as stabilizing agent
General procedure for the synthesis of quinoxaline/imidazole
A 25 mL round-bottom fask was charged with a mixture of Benzil/aldehyde
(1 mmol), ortho phenylene diamine (OPD) (1 mmol) and 5 mol% of FeNPs. The
mixture was stirred in water at room temperature (31 °C) about 5–10 min. The
completion of reaction was monitored by TLC and solid was separated by fltra-
tion/centrifuge, on pouring the mixture into ice cold water. The obtained product
was recrystallized in ethanol to aford the pure product.
General procedure for the synthesis of pyrazole
A 25 mL round-bottom fask was charged with a mixture of acetyl acetone
(1 mmol), phenyl hydrazine (1 mmol) and 5 mol% of FeNPs. The mixture was
stirred in water at room temperature (31 °C) about 5–10 min. The completion of
reaction was monitored on TLC and solid was separated by fltration/centrifuge,
1 3

S. M. Arde et al.
on pouring the mixture into ice cold water. Obtained product was recrystalized in
ethanol to aford the pure product.
Results and discussion
Initially, the black suspension of biosynthesized material was monitored via UV–Vis
spectroscopy. Figure 2 displayed the UV–visible spectra of (a) Boswellia serrata
aqueous PE, (b) Acacia concinna aqueous pod extract, (c) FeSO4 aqueous solution
and (d) FeNPs black suspension at room temperature after 3 h. The strong surface
plasmon resonance band of FeSO4 appeared at 345 nm (c) was disappeared in (d)
spectra indicated that complete reduction of Fe++ to Fe0 within 3 h converting grad-
ually faint yellow solution into black suspension.
Next, we have studied the physical parameters with respect to pH and potential
diference of the PE, surfactant, and black suspension before and after completion of
the reaction and results are summarized in Table 1a, b.
According to electrochemical series, it is indicated that Fe++ ions can be reduced
when PE or any other reducing agents should have potential diference (reduction
potential) greater than −0.41. Considering above statement, fortunately, potential
diference of aqueous extract of Boswellia sarrata leaves was found to be −0.65 V,
and hence reduction of Fe++ could be possible by the selected plant material.
As synthesized nanoparticles were agglomerated in the solution, stability of
material checked in diferent biosurfactants and results are displayed in Table 2.
From Table 2, it is concluded that, Acacia concinna aqueous pod extract (acidic bio-
surfactant, pH 3.11) is suitable stabilizing agent for the synthesis of FeNPs that is
stability of respective nanoparticles is pH sensitive. Thus it can be presumed that
plant extract with high reductant capacity and acidic pH will be best suited for the
synthesis of iron nanoparticles [15].
Fig. 2 UV–visible spectra of biosynthesized nanomaterials
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
Table 1 Study of (a) pH change, (b) potential diference change
S. no.
Solutions
pH
(a)
1.
2.
3.
4.
Boswellia sarrata leaves aq. extract
Acacia concinna pod aq. extract
FeSO4 Solution
4.36
3.11
5.01
3.05
Black suspension of synthesized nanomaterials
S. no.
Solutions
Potential diference
(b)
1.
2.
3.
4.
Boswellia sarrata leaves aq. extract
Acacia concinna pod aq. extract
FeSO4 solution
−0.650
+0.085
+0.040
+0.175
Black suspension of synthesized nanomaterials
Table 2 The efect of
biosurfactants toward
the stability of the iron
nanoparticles
S. no.
Biosurfactant
pH
Stability toward
biosynthesized
FeNPs
1.
2.
3.
Sapindus mukorossi (Ritha)
Balanites rosburghii
Acacia concinna
6.43
5.54
3.11
Not stable
Not stable
Stable
Fig. 3 a XRD pattern and b SAED Pattern of biosynthesized nanomaterials
The XRD report of biosynthesized FeNPs (Fig. 3a) showed the dense descend-
ing slope with no sharp peaks. Lack of distinct XRD pattern suggesting that FeNPs
are amorphous in nature and for ultra-small crystalline materials where difraction
peaks cannot be well resolved. In support to this, the SAED pattern/micrograph does
1 3

S. M. Arde et al.
Fig. 4 a SEM and b EDS spectrum of biosynthesized nanomaterials
not have any clear difraction rings or spot pattern but show a difuse ring confrm-
ing the FeNPs is amorphous in nature (Fig. 3b).
The morphology of biosynthesized nanomaterials has been confrmed from SEM
study. The FE-SEM image (Fig. 4a) indicated the formation of the rectangle and
nearly uniform sized FeNPs. Elemental analysis was carried out by using EDS anal-
ysis (Fig. 4b). The presence of a great deal of Fe atoms with other atoms includ-
ing phosphorous, calcium, oxygen, chlorine [36] is clearly evident from the spec-
trum, which indicates the presence of residual phytomolecules of the plant extract
as capping ligands on the surfaces of the FeNPs. Biosynthesized black powder on
EDS analysis displays an optical absorption peak at 6.4 keV, which is typical of the
absorption of iron.
The uniformity and particle size of biosynthesized FeNPs were investigated using
TEM analysis (Fig. 5) and particle size distribution graph. The particles are distrib-
uted in the range 15–25 nm. According to the electron micrographs, the FeNPs is
predominantly rectangular/oval in shape with an average particle size of 19 3 nm.
Fig. 5 TEM image of FeNPs with particle size distribution graphs
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
Fig. 6 a Full survey XPS and b XPS spectrum of Fe 2p-electrons
Fig. 7 TGA analysis of FeNPs
100
90
80
70
60
50
40
30
0
200
400
600
800
1000
Temperature (°C)
The presence some larger particles can be attributed to the aggregation or overlap-
ping of smaller particles.
BET analysis provides precise specifc surface area evaluation of the materials.
The biosynthesized FeNPs found that BET surface area equals to 59 m2/g.
Overview of XPS spectrum of iron containing NPs produced from Boswellia
serrata aqueous leaves extract (Fig. 6), indicates lines of carbon, oxygen, phos-
phorus, iron, and nitrogen. In the XPS spectrum of Fe 2p-electrons (Fig. 6b), dis-
tinct states of the iron atoms at 711.68 eV was observed, which correspond to
the binding energy electron components of Fe 2p3/2. Such binding energies were
typical for trivalent and divalent iron atoms respectively25. However, the absence
of a distinct satellite peak could be observed in Fig. 6b. There was a mild peak at
707.78 eV, corresponding to Fe0. As the Fe nanoparticles were exposed to the air
in the process of sample preparation and testing, the Fe0 was oxidized, hence the
weakness of the peak at 707.78 eV. Therefore, the nanoparticles synthesized in
1 3

S. M. Arde et al.
extracts of Boswellia serrata aqueous leaves extract mainly contained nano-Fe3O4
and Fe0 based on XPS spectrum.
In the TGA curve (Fig. 7), it was observed that three regions with diferent
slopes are recognized. In the frst region 40–153°C, weight loss is attributed to
the vaporization of water and the degradation of volatile organic materials loosely
bonded on the surface of the FeNPs. Further increase in heat fow results in pro-
gressive weight loss which indicates that the FeNPs material is unstable at high
temperature.
With the above characterization, catalytic activity of FeNPs has explored for
the synthesis of biological active N-heterocyclic compounds namely quinoxa-
lines, benzimidazole and pyrazole derivatives in water at room temperature. As
aqueous media propose many practical, economical, and ecological advantages
over organic solvents, it is benefcial to use as a reaction solvent because it is safe,
harmless, and environmentally friendly [37].
Catalytic activity of FeNPs frstly tested with the synthesis of quinoxaline.
The condensation reaction of benzil with ortho phenylene diamine (OPD) was
used as a model reaction to investigate the catalytic performance of FeNPs and
the efect of media upon the reaction. In the absence of catalyst the product 3a
(Table 5, entry 1) was produced with very trace amount after 10 h of stirring in
water (Table 3, entry 1), but on addition of FeNPs (5 mol% in comparison with
Table 3 Optimization studies for the synthesis of quinoxaline
S. no.
Reaction medium
FeNPs
Time
Reaction condition
Yielda (%)
(mol%)
1
2
3
4
5
6
7
8
Water
Ethanol
Acetonitrile
DMF
Acetone
–
–
–
–
–
5
5
5
5
5
5
5
10 h
10 h
10 h
10 h
r.t./refux
r.t./refux
r.t./refux
r.t./refux
r.t./refux
r.t.
r.t.
r.t.
r.t.
r.t.
Trace
Trace
Trace
Trace
Trace
98
95
81
80
90
10 h
H2O
5 min
8 min
15 min
20 min
15 min
20 min
30 min
Ethanol:water (1:1)
Ethanol
Acetone
Acetone:water (1:1)
DMF
CH3CN
9
10
11
12
r.t.
r.t.
68
60
Reaction conditions: benzil (1 mmol), o-phenylenediamine (1 mmol), Solvent (5 mL), FeNPs (catalytic
amount)
aIsolated yield
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
the other reported catalyst [38, 39]) in reaction mixture, conversion of substrate
to product was suddenly increased up 98% in 5 min (Table 3, entry 6). There is a
noticeable diference in the product yield between water and organic solvent. This
might be due to dispersion of catalyst in the solvent. Biosynthesized FeNPs was
amorphous in nature (Fig. 3) and well dispersed in the water, whereas in organic
solvent, it was aggregated and settled down. This might be the reason that the
yield of the product is low in organic solvent as compared to water.
With these results in hand, we have determined the FeNPs concentration for max-
imum yield of the product in water. Thus, the model reaction was carried out with
various concentrations (mol%) of FeNPs in water at ambient temperature. By chang-
ing concentration, dramatic efect on the conversion rate of quinoxaline has been
observed. As shown in Table 4, linear relationship was observed with concentration.
The yield of the product is highest at 5 mol% of FeNPs catalyst. On the other hand,
further increase in concentration resulted in no increase or decrease in the product
yield.
To explore the scope and generality of the catalyst, the optimized protocol
[o-phenylenediamine (1.0 mmol), benzil (1.0 mmol), water (5 mL), at room tem-
perature under air] was applied for reactions of variety of o-phenylenediamine and
1,2 diketone with moderate to excellent yield (80–98%).
According to experimental results, high reaction rates and yields were obtained
with both activated and non-activated benzils (Table 5, entry 1–10). Benzils with-
out any substituent and activated benzils with electron-withdrawing substituents are
reactive substrates in quinoxaline synthesis and the related reactions went to com-
pletion in shorter reaction times. As an example, the reaction of benzil with OPD
completed within 5 min giving the desired product in 98% isolated yield (Table 5,
entry 1). Non-activated benzil with electron-donating substituent on the aromatic
ring are not reactive substrates in quinoxaline synthesis and related reactions com-
pleted in longer reaction times (Table 5 in entry 3).
Inspired from these results, we have explored the scope of FeNPs for the syn-
thesis of benzimidazole, instead of benzil, benzaldehyde was reacted with OPD
(Scheme 1) at room temperature in aqueous medium. Reaction was completed
within 5 min with excellent yield in aqueous medium with use of 5 mol% of cata-
lyst. To explore the scope and generality of the catalyst, the optimized protocol for
Table 4 Optimization of catalyst
Entry
Catalyst (mol%) Time (min)
Yielda (%)
for quinoxaline synthesis
1
2
3
4
5
6
1
2
3
4
5
6
45
25
15
15
5
40
52
75
84
98
98
5
Reaction conditions: o-phenylenediamine (1 mmol), benzil
(1 mmol), water (5 mL), RT
aIsolated yields after purifcation
1 3

S. M. Arde et al.
Table 5 Synthesis of quinoxaline and its derivatives by FeNPs
Time
( min)
Yielda
( % )
Entry 1,2-diamine
1,2-diketone
Product
1
5
98
1a
2a
3a
2
91
12
1a
2b
2c
3b
3
15
85
93
1a
3c
4
7
1a
2d
3d
3e
5
15
92
80
1a
2e
6
25
2a
1b
3f
7
86
92
25
10
1b
2d
2a
3g
8
1c
3h
9
92
25
10
1c
2b
2d
3i
3j
10
93
1c
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
Table 5 (continued)
Reaction conditions: diketone (1 mmol), OPD (1 mmol), FeNPs catalyst (5 mol%), water 5 mL, RT
aIsolated yields
O
O
R1
R1
H
N
R1
OHC
N
N
H2N
H2N
R1
R2
FeNPs 5 mol%
Water R.T.
N
Fe NPs 5 mol%
Water R. T.
R3
R3
R2
Scheme 1 Synthesis of quinoxaline and benzimidazole
benzimidazole was applied for reactions of variety of aldehydes and o-phenylenedi-
amine with moderate to excellent yield (93–78%) (Table 6).
Pyrazole is one of the fve member heterocyclic compound containing two
nitrogen atoms present at 1, 2 positions. We also tried for the synthesis of pyra-
zole in the presence of FeNPs as a catalyst in aqueous medium at room tempera-
ture. The results obtained are summarized in Table 7. The optimized protocol
was applied for reactions of variety of phenyl hydrazine and acetyl acetone with
moderate to excellent yield (92–75%).
Plausible reaction mechanism
The plausible reaction mechanism for the synthesis of quinoxaline derivatives
are shown in Scheme 2. The mechanism proceeds by oxidative addition of
FeNPs on carbonyl oxygen of benzil (1) followed by the nucleophilic attack of
lone pair of nitrogen of OPD (2, 3) on activated carbonyl carbon. Same process
of mechanism (4) is repeated for second carbonyl oxygen of benzil to form six
membered cyclic intermediate (5). Further, the six-membered cyclic intermedi-
ate (5) abstract protons from solvent leaving behind FeNPs to form dihydroxy
intermediate (6). This (6) on dehydration yields desired product (7).
1 3

S. M. Arde et al.
Table 6 Synthesis of benzimidazoles its derivatives in aqueous medium by using 5 mol% FeNPs
Entry
Aldehyde
Product
Time
(Min)
Yielda
(%)
CHO
1
5
93
5a
4a
CHO
2
3
30
83
OMe
4b
5b
5c
CHO
25
25
78
80
OH
4c
4
5
4d
5d
5e
5f
25
86
4e
CHO
30
15
88
87
6
Cl
4f
CHO
7
8
NO2
5g
5h
4g
20
20
88
80
4h
4i
9
5i
Reaction conditions: aldehyde (1 mmol), o-phenylenediamine (1 mmol), FeNPs catalyst (5 mol%), water
5 mL, RT
aIsolated yields after recrystallization
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
Table 7 Synthesis of pyrazoles in aqueous medium by using 5 mol% FeNPs
Hydrazine/
Hydrazide
Reaction
Time (min)
Yielda
(%)
Entry
Product
1
15
92
7a
7b
8a
2
3
30
87
8b
40
82
7c
8c
4
5
80
90
30
80
78
77
7d
7e
7f
8d
8e
8f
6
7
50
5 h
83
77
75
7g
8g
8
9
7h
8h
12 h
7i
8i
8j
10
40
84
7j
11
12
15
25
90
90
7k
8k
8l
7l
1 3

S. M. Arde et al.
Table 7 (continued)
Reaction conditions: phenyl hydrazine (1.2 mmol), reaction medium (5 mL), acetyl acetone (1 mmol),
FeNPs (5 mol%)
aIsolated yields
FeNPs
FeNPs
H2N
H
N
O
O
O
O
O
FeNPs
FeNPs
O
NH2
H2N
3
FeNPs
2
1
4
H
H
O
O
H
N
O
N
N
+2H+
FeNPs
N
-2H2O
N
H
N
H
O
H
7
6
FeNPs
5
Scheme 2 Plausible reaction mechanism for quinoxaline model reaction (Table 5, entry 1)
Reusability
For practical applications of homogeneous systems, the lifetime of the catalyst
and its level of reusability are very important features. The recyclability of cat-
alyst was investigated with consecutive quinoxaline synthesis by taking o-phe-
nylenediamine (1 mmol), benzil (1 mmol) in aqueous medium at room tem-
perature. After the completion of frst cycle, the product was extracted by ethyl
acetate and the catalyst was recovered by centrifugation and extensively washed
Fig. 8 Reusability of FeNPs
catalyst in quinoxaline, pyra-
zole, and imidazole synthesis
1 3

Synthesis of quinoxaline, benzimidazole and pyrazole…
with water, dichloromethane and acetone. The catalyst was then dried under
vacuum before performing the reusability test. The recycling results of catalyst
were summarized in Fig. 8. After the frst cycle, activity of catalyst is decreased
with decreasing yield from 98 to 84% with increased time. The same process was
repeated in the syntheses of benzimidazole and pyrazole and the collective reus-
ability graph is shown below.
Conclusions
In summary, we have demonstrated an efcient, simple, economical and environ-
mentally benign protocol for the synthesis of FeNPs by using Boswellia serrata
aqueous leaves extract and its catalytic applications in the synthesis of quinoxalines,
benzimidazole and pyrazole derivatives in an aqueous medium at room temperature.
Biosynthesized FeNPs were stabilized in aqueous pod extract of Acacia concinna,
a natural surfactant (pH 3.11). The size of FeNPs was characterized by TEM analy-
sis and it was~19 nm. The amorphous nature of FeNPs was analyzed by XRD and
SAED analysis and used as a non-toxic, inexpensive, heterogeneous catalyst in an
aqueous medium. It was recycled up to fve cycles with modest change in catalytic
activity. Thus, the catalytic protocol developed provides an unprecedented reactivity
pattern, an economically attractive and environmentally benign alternative route for
the production of quinoxaline, benzimidazole, pyrazole and widens the synthesis of
related compounds in organic syntheses.
References
1. M. Khan, M. Khan, M. Kuniyil, S.F. Adil, A. Al-Warthan, H.Z. Alkhathlan, W. Tremel, M.N. Tahir,
M. Rafq, H. Siddiqui, Dalton Trans. 43, 9026 (2014)
2. O.A. Guselnikova, A.I. Galanov, A.K. Gutakovskii, P.S. Postnikov, Beilstein J. Nanotechnol. 6,
1192 (2015)
3. J. Ruusunen, M. Ihalainen, T. Koponen, T. Torvela, M. Tenho, J. Salonen, O. Sippula, J. Joutsen-
saari, J. Jokiniemi, A. Lahde, J. Nanopart. Res. 16, 2270 (2014)
4. M. Kim, K. Park, T. Lim, S. Choe, T. Yu, J.J. Kim, J. Electrochem. Soc. 160(1), E1 (2013)
5. A. Szpak, G. Kania, T. Skorka, W. Tokarz, S. Zapotoczny, M. Nowakowska, J. Nanopart. Res. 15,
1372 (2013)
6. K. Byrappa, S. Ohara, T. Adschiri, Adv. Drug Deliv. Rev. 60, 299 (2008)
7. R. Oremland, M. Herbel, J. Blum, S. Langley, T. Beveridge, P. Ajayan, T. Sutto, A. Ellis, S. Curran,
Appl. Environ. Microbiol. 70(1), 52 (2004)
8. K. Narayanan, N. Sakthivel, Adv. Colloid Interface Sci. 156, 1 (2010)
9. K.V. Pavani, N.S. Kumar, Am. J. Nanomater. 1(2), 24 (2013)
10. S.M. Arde, P.R. Salokhe, A.H. Mane, R.S. Salunkhe, Chem. Sci. Rev. Lett. 3(11), 557 (2014)
11. N.L. Gavade, A.N. Kadam, M.B. Suwarnkar, V.P. Ghodake, K.M. Garadkar, Spectrochim. A Mol.
Biomol. Spectrosc. 136, 953 (2015)
12. T. Santhoshkumar, A.A. Rahuman, A. Bagavan, S. Marimuthu, C. Jayaseelan, A.V. Kirthi, C.
Kamaraj, G. Rajakumar, A.A. Zahir, G. Elango, K. Velayutham, M. Iyappan, C. Siva, L. Karthik,
K.V.B. Rao, Exp. Parasitol. 132, 156 (2012)
13. S. Iravani, Green Chem. 13, 2638 (2011)
1 3

S. M. Arde et al.
14. S. Gnanasekar, G. Chandrakasan, K. Karuppiah, H. Vedagiri, P. Kumpati, S. Sivaperumal, Colloids
Surf. B Biointerfaces 95, 235 (2012)
15. V.V. Makarov, S.S. Makarova, A.J. Love, O.V. Sinitsyna, A.O. Dudnik, I.V. Yaminsky, M.E. Talian-
sky, N.O. Kalinina, Langmuir 30(20), 5982 (2014)
16. S. Peng, C. Wang, J. Xie, S. Sun, J. Am. Chem. Soc. 128, 10676 (2006)
17. E. Carenza, V. Barcelo, A. Morancho, J. Montaner, A. Rosell, A. Roig, Acta Biomater. 10, 3775
(2014)
18. Y. Sun, X. Li, J. Cao, W. Zhang, H.P. Wang, Adv. Colloid Interface Sci. 20, 47 (2006)
19. S. Cheong, P. Ferguson, K. Feindel, I. Hermans, P. Callaghan, C. Meyer, A. Slocombe, C. Su, F.
Cheng, C. Yeh, B. Ingham, M. Toney, R. Tilley, Angew. Chem. Int. Ed. 50, 4206 (2011)
20. L. Guo, Q. Huang, X. Li, S. Yang, Phys. Chem. Chem. Phys. 3, 1661 (2001)
21. S. Ponder, J. Darab, J. Bucher, D. Caulder, I. Craig, L. Davis, N. Edelstein, W. Lukens, H. Nitsche,
L. Rao, D. Shuh, T. Mallouk, Chem. Mater. 13, 479 (2001)
22. E.E. Carpenter, J. Magn, Magn. Mater. 225, 17 (2001)
23. C. Wang, W. Zhang, Environ. Sci. Technol. 31(7), 2154 (1997)
24. G. Jaiswal, V.G. Landge, D. Jagadeesan, E. Balaraman, Green Chem. 18, 3232 (2016)
25. Y. Wei, Z. Fang, L. Zheng, E.P. Tsang, Appl. Surf. Sci. 399, 322 (2017)
26. C. Antonio, P. Giuseppe, M. Nikookar, S. Paolo, S. Leonardo, Z. Stefania, Eur. J. Med. Chem. 37,
355 (2002)
27. B. Gao, D. Xia, Y. Geng, Y. Cheng, L. Wang, Tetrahedron Lett. 51, 1919 (2010)
28. S. Bhattacharya, P. Choudhuri, Curr. Med. Chem. 15, 1762 (2008)
29. S.B. Kamble, G.S. Rashinkar, A.S. Kumbhar, K.B. Mote, R.S. Salunkhe, Synth. Commun. 42(5),
756 (2012)
30. D. Kam, K. Kim, H. Liu, Electrochem. Commun. 11, 1657 (2009)
31. A. Patil, R. Salunkhe, Res. Chem. Intermed. 44, 3337 (2018)
32. T. Lohar, A. Kumbhar, A. Patil, S. Kamat, R. Salunkhe, Res. Chem. Intermed. 45, 639 (2019)
33. A. Patil, A. Mane, S. Kamat, T. Lohar, R. Salunkhe, Res. Chem. Intermed. 45, 3441 (2019)
34. A. Patil, S. Gajare, G. Rashinkar, R. Salunkhe, Catal. Lett. 150, 127 (2020)
35. A. Patil, T. Lohar, A. Mane, S. Kamat, R. Salunkhe, J. Heterocycl. Chem. 56, 3145 (2019)
36. R. Bawankar, P. Singh, B. Subramanian, J. Plant Sci. 2, 102 (2014)
37. S. Venkateswarlu, B.N. Kumar, C.H. Prasad, P. Venkateswarlu, N.V.V. Jyothi, Phys. B 449, 67
(2014)
38. K. Holmberg, Curr. Opin. Colloid Interface Sci. 8, 187 (2003)
39. A.R. Siamaki, B.A. Arndtsen, J. Am. Chem. Soc. 128, 6050 (2006)
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