Facile fabrication of porous magnetic covalent organic frameworks as robust platform for multicomponent reaction

Article abstract of DOI:10.1002/aoc.6373

The design of cheap yet efficient nanoporous magnetic catalysts for the environmentally benign process's widespread application is an extremely attractive, challenging chemical research field. A novel porous magnetic covalent organic framework was prepared by the condensation reaction of melamine and terephthaladehyde on the surface of 3,4-dihydroxybenzaldehyde coated magnetic Fe₃O₄ nanoparticles COF@Fe₃O₄ under hydrothermal conditions for the first time. The high surface area magnetic COF could exhibit superior catalytic activity for sustainable synthesis of trisubstituted and tetrasubstituted imidazoles and pyrroles in good to excellent yields in PEG as solvent under environmentally friendly, ambient conditions and making the overall process economical, efficient, and green. The retrievable catalyst in PEG is general and applicable to a broad substrate scope and functional group compatibility. The structure and morphology of the COF@Fe₃O₄ were characterized by FTIR, XRD, EDX, and SEM spectroscopy. The COF@Fe₃O₄ magnetic catalyst was recovered by an external magnet and used for several cycles without significant catalytic activity loss.

Full text of DOI:10.1002/aoc.6373

Received: 28 April 2021
DOI: 10.1002/aoc.6373
Revised: 23 June 2021
Accepted: 30 June 2021
R E S E A R C H A R T I C L E
Facile fabrication of porous magnetic covalent organic
frameworks as robust platform for multicomponent
reaction
Najmedin Azizi
| Fatemeh Heidarzadeh
| Fezeh Farzaneh
Department of Green Chemistry,
Abstract
Chemistry and Chemical Engineering
Research Center of Iran, Tehran, Iran
The design of cheap yet efficient nanoporous magnetic catalysts for the envi-
ronmentally benign process's widespread application is an extremely attractive,
challenging chemical research field. A novel porous magnetic covalent organic
framework was prepared by the condensation reaction of melamine and ter-
ephthaladehyde on the surface of 3,4-dihydroxybenzaldehyde coated magnetic
Fe3O4 nanoparticles COF@Fe3O4 under hydrothermal conditions for the first
time. The high surface area magnetic COF could exhibit superior catalytic
activity for sustainable synthesis of trisubstituted and tetrasubstituted imidaz-
oles and pyrroles in good to excellent yields in PEG as solvent under environ-
mentally friendly, ambient conditions and making the overall process
economical, efficient, and green. The retrievable catalyst in PEG is general and
applicable to a broad substrate scope and functional group compatibility. The
structure and morphology of the COF@Fe3O4 were characterized by FTIR,
XRD, EDX, and SEM spectroscopy. The COF@Fe3O4 magnetic catalyst was
recovered by an external magnet and used for several cycles without significant
catalytic activity loss.
Correspondence
Najmedin Azizi, Department of Green
Chemistry, Chemistry and Chemical
Engineering Research Center of Iran,
P.O. Box 14335-186, Tehran, Iran.
Email: azizi@ccerci.ac.ir
Funding information
Iran National Science Foundation, Grant/
Award Number: 98015375
K E Y W O R D S
green chemistry, imidazole derivatives, magnetic catalyst, multicomponent reaction,
porous magnetic covalent organic frameworks
1 | INTRODUCTION
sensors, and ion conduction membranes.[3,4] COFs are
two-dimensional (2D) or three-dimensional (3D) crystal-
The use of functionalized porous materials with high
surface area as a heterogeneous catalyst and appealing
support has received considerable attention in the last
decade.[1,2] For example, zeolites are widely used as
active catalysts in the petrochemical and refining
industries. Amorphous porous organic polymers such as
crystalline metal–organic frameworks (MOFs) and
covalent organic frameworks (COFs) have been
proposed as new candidates for various applications,
including heterogeneous catalysis, gas storage, drug
delivery, chromatography separation, electrochemical
line polymer networks with well-defined nanopores that
are formed by strong covalent bonds between light-
weight elements such as B, C, N, O, and Si.[5–8] COFs
are considered a unique, organic polymer with intrinsic
properties including large surface area, high thermal
stability, low density, and superior oxidative and
hydrolytic stability in water and organic solvents.[9–14]
However, the solubility of COFs in polar solvents and
water hinders their development in the catalytic system
due to the separation problems.[15–19] To overcome this
drawback and develop efficient catalytic processes, one
Appl Organomet Chem. 2021;e6373.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
1 of 13
https://doi.org/10.1002/aoc.6373

2 of 13
AZIZI ET AL.
must load COFs onto a magnetic nanoparticle, which
can serve as a novel strategy for easy separation of COF
in the catalytic cycles. Additionally, magnetic
nanoparticles (MNPs) can be quickly separated from the
reaction mixture via an external magnet, facilitating the
work-up procedure and shortening reaction times.
Regarding the features of COF and Fe3O4, we
attempted to prepare COF functionalized MNPs and
apply them as a reusable magnetic catalyst in organic
synthesis.
2 | EXPERIMENTAL
2.1 | General
All chemicals and solvents were obtained from a com-
mercially available source and used without further puri-
fication. Melting points were recorded on a Buchi
535 melting point apparatus. 1H NMR spectra were
recorded on 500 or 300 MHz NMR spectrometer, and 13C
NMR spectra were recorded on 125 MHz NMR spectrom-
eter, respectively, using CDCl3 or DMSO, as a solvent.
Chemical shifts have been expressed in (ppm) downfield
from TMS. FT-IR spectra were obtained on a Bruker
Vector-22 infrared spectrometer using KBr disks. The
morphological and EDX studies were carried using a
Scanning Electron Microscope TESCAN Vega Model.
Heterocyclic small molecules have an essential role in
the search for new therapeutic and drug materials.
Nitrogen-containing heterocycles represent significant
structural units that display a large spectrum of biological
activities, agrochemicals, pharmaceuticals, and func-
tional materials.[20] Five-membered nitrogen heterocycles
such as imidazoles are widely used in chemical and bio-
logical systems.[21–23] Many of the substituted imidazoles
are known as inhibitors of fungicides and herbicides,
therapeutic agents, and plant growth regulators.[24,25]
Numerous published methodologies for synthesizing
these substituted imidazoles are because of their
widespread biological applications.[26–31] However, the
reported protocols are not usable and affordable due to
disadvantages such as dangerous solvents, expensive
instruments, high reaction temperature, corrosive
reagents, and the neutralization necessity of the
vital acid media.[32–38] Pyrroles are essential heterocyclic
compounds with significant pharmacological properties
such as antiviral, antibacterial, antitumoral, anti-
inflammatory, and antioxidant activities. Due to the great
importance and application of pyrroles, there is a great
desire and attention to its synthesis recently. There are
numerous approaches to synthesizing pyrroles, and
Paal–Knorr, Clauson–Kaas, Barton–Zard, and Hantzsch
reactions are well explored in the literature.[39,40] The
Paal–Knorr method is one of the most popular and
most economical and convenient procedures essential
and valuable biologically and pharmacologically active.
In the classical Paal–Knorr reaction, 1,4-dicarbonyl
compounds were reacted with primary amines in the
presence of boiling acetic acid for extended times. The
broad applications of pyrrole annulated heterocyclic
scaffolds have drawn substantial attention, and many
catalysts and protocols have been developed in
recent years.[41–46] However, some problems remained
unresolved, such as low-to-moderate yields, toxic and
moisture-sensitive reagents, and catalysts, expensive,
tedious work-up, and difficulties in separation and
recovery of catalysts. Thus, to solve these problems,
highly efficient and eco-friendly synthetic protocols
for the synthesis of pyrrole derivatives should be
achieved.
2.2 | Preparation of magnetic catalyst
[COF@Fe3O4]
The magnetic Fe3O4 nanoparticle was prepared according
to Massart's method.[39] The functionalization of the car-
bonyl group on Fe3O4 nanoparticle (Fe3O4–CHO) is illus-
trated in Scheme 1. In a typical procedure, Fe3O4 (2.0 g)
was dispersed into choline chloride-urea (2:1) based deep
eutectic solvent (60 ml) with sonication for 30 min, and
then 3,4-dihydroxybenzaldehyde (2.0 g) was added the
reaction mixture was heated at 80ꢀC under nitrogen for
12 h. The obtained Fe3O4–CHO was cooled to room tem-
perature, collected by a magnet, washed several times
SCHEME 1 Synthesis of COF@Fe3O4

AZIZI ET AL.
3 of 13
with ethyl acetate, dried at 60ꢀC in a vacuum. Then, mel-
amine (1.0 g, 8 mmol) and Fe3O4–CHO (0.3 g) were first
dissolved in 40 ml of dimethyl sulfoxide (DMSO) at
100ꢀC, then terephthaladehyde (1.6 g, 12 mmol) and
LiClO4 (3.0 g) were added, and the mixture was refluxed
at 135ꢀC for 72 h under nitrogen. The reaction mixture
cooled to room temperature, and the resulting
COF@Fe3O4 catalyst was washed with ethyl acetate and
methanol and was dried under vacuum at 80ꢀC for 24 h
(Scheme 1).
120–300 min. (TLC followed the progress of the reaction.)
After completing the reaction, ethanol (10 ml) was added,
and COF@Fe3O4 was separated from the reaction
mixture using an external magnet. Crude products were
recrystallized from a mixture of ethyl acetate and
petroleum ether (1:10) or column chromatography to give
pure pyrrole derivatives. The products were identified by
comparing melting point with those reported in the
literature.
3 | RESULTS AND DISCUSSION
2.3 | Typical experimental procedure for
the synthesis of 2,4,5-trisubstituted
imidazoles
Over the past few years, we have designed more
reasonable and eco-friendly organic transformations
using cheap and non-toxic catalysts and solvents by
fulfilling green and sustainable chemistry.[47–49] Herein,
we report a novel magnetic COF-based nanocomposite as
a new separable and active heterogeneous catalyst in
an eco-friendly solvent for the robust synthesis
of 2,4,5-trisubstituted, 1,2,4,5-tetrasubstituted imidazoles
and pyrrole derivatives under mild reaction
conditions. Fe3O4 nanoparticles were prepared by the
hydrothermal method and then were coated by
3,4-dihydroxybenzaldehyde. The hydrothermal reaction
of the terephthaladehyde and melamine on the surface of
3,4-dihydroxybenzaldehyde coated Fe3O4 nanoparticles
produces a desired magnetic catalyst.
A mixture of benzaldehyde (1.0 mmol), benzil (1.0 mmol),
ammonium acetate (3.0 mmol), and COF@Fe3O4
(30 mg) was stirred at room temperature in PEG
200 (2.0 ml) for 2–5 h, and TLC followed the progress of
the reaction. On completion of the reaction, the magnetic
COF was separated by an external magnet. Then the
water (10 ml) was added, and the resulting solid residue
was recrystallized from ethyl acetate or ethanol to afford
the desired pure products 3a. All products were identified
by NMR spectroscopy and melting point analysis by
comparing them by reference standards.
2.4 | General procedure for the synthesis
of 1,2,4,5-tetrasubstituted imidazoles
3.1 | Characterization of
Fe3O4@3,4-dihydroxybenzaldehyde
nanoparticles
A mixture of benzil (1.0 mmol), aldehyde (1.0 mmol), pri-
mary amine (1.0 mmol), ammonium acetate (1.2 mmol),
and COF@Fe3O4 (30 mg) in PEG 200 (2.0 ml) was put
into a 5-ml round-bottom flask. The flask was stirred at
80ꢀC for 80–250 min (checked by TLC). After the reac-
tion was complete, the mixture was cooled to ambient
temperature, and an external magnet separated the mag-
netic COF. After the addition of water (10 ml), the solid
product obtained was recrystallized from ethyl acetate or
ethanol to afford the pure product, which required no
further purification. All products were identified by NMR
spectroscopy and melting point analysis by comparing
them by reference standards.
The structure and morphology of the Fe3O4@3,4-
dihydroxybenzaldehyde were characterized by FTIR,
XRD, EDS, and SEM spectroscopy.
The functionalization of 3,4-dihydroxybenzaldehyde
on Fe3O4 nanoparticles was approved by Fourier
2.5 | General procedure for the synthesis
of the pyrrole
A mixture of primary amine (1.0 mmol), 2,5-hexanedione
(1.0 mmol), and COF@Fe3O4 (30 mg) under solvent-free
conditions was stirred at room temperature for
FIGURE 1 FT-IR spectra of Fe3O4@3,4-dihydroxybenzaldehyde

4 of 13
AZIZI ET AL.
transform Infrared (FTIR) spectroscopy, and the results
are shown in Figure 1. The robust and intense Fe-O
vibration mode is revealed in 588 cmÀ1, and the broad
peaks appeared at 3350 cmÀ1 in correspond to O–H
stretching and bending vibrations, respectively.
The microstructure and surface morphology of
Fe3O4@3,4-dihydroxybenzaldehyde were investigated by
SEM analysis, and the results are shown in Figure 3. As
clearly seen in Figure 3, the prepared magnetic
nanoparticles are composed of ultrafine particles in the
nanometer size range of 25 nm with a high homogeneous
cubic shape. Moreover, the EDS analysis results
(Figure 4) showed the expected element composition
of C, O, and Fe further suggests the successful func-
tionalization of Fe3O4 with aldehydes. In addition, the
amount of aldehyde functional groups of Fe3O4 was 18%
calculated by EDS and CHN analysis.
3,4-Dihydroxybenzaldehyde
functionalized
Fe3O4@
nanoparticles gave additional peaks such as C=C
stretching at 1400–1600 cmÀ1 and C=O at 1680 cmÀ1
(Figure 1).
X-ray diffraction analysis (XRD) is used to study the
crystalline structure of Fe3O4@3,4-dihydroxybenzaldehyde
(Figure 2). The XRD pattern showed that the Fe3O4 nano-
particle was well crystallized and had a cubic morphology
without impurities. Furthermore, the XRD pattern of
Fe3O4@3,4-dihydroxybenzaldehyde indicates that the crys-
talline structure of Fe3O4 has not notable changed after
the surface modification with an aldehyde (Figure 2).
After
preparation
and
characterization
of
Fe3O4@3,4-dihydroxybenzaldehyde, the growth of the
COFs around the Fe3O4 nanoparticles has been com-
pleted through the reaction of the magnetic nanoparticles
with melamine and the subsequent in situ formation of
COF crystalline with embedded Fe3O4 particles. The
structure and morphology of the COF@Fe3O4 were char-
acterized by FTIR, XRD, EDX, and SEM spectroscopy.
The FTIR spectrum of COF@Fe3O4 is presented in
Figure 5. The broad peak related to the Fe–O band was
observed around 576 cmÀ1 that is the characteristic peak
of Fe3O4 nanoparticle in the catalyst. For COF, the
vibrational peak of C=N stretching band at 1552 cmÀ1
,
aromatic C–C ring stretching at 1442 cmÀ1, and the
stretching vibration of C=O (amide) at 1647 cmÀ1 were
observed. Additionally, the broad peak in the reign of
3418 cmÀ1 is related to NH groups' stretching vibration
and adsorbed water molecules.
The elemental distribution and the chemical composi-
tion of the catalyst were further analyzed by EDS map-
ping (Figure 6). The EDS spectrum confirms Fe, C, O,
and N elements in the sample. Besides, the EDS maps of
the catalyst display predominantly COF, while Fe3O4 is
hardly detectable. Furthermore, EDS elemental analysis
shows a Fe3O4 core surrounded by a thick COF shell.
FIGURE 2 XRD pattern of Fe3O4@3,4-dihydroxybenzaldehyde
FIGURE 3 Representative SEM images of Fe3O4@
3,4-dihydroxybenzaldehyde
FIGURE 4 EDS analysis of Fe3O4@3,4-dihydroxybenzaldehyde

AZIZI ET AL.
5 of 13
FIGURE 5 FT-IR spectra of COF@Fe3O4
nanoparticles' shell. However, the incorporation of thick
shell COF changed the crystal structure of Fe3O4
nanoparticles.
The SEM image indicated that COF formed a cluster-
like morphology (Figure 8). The morphological specifica-
tions of COF remain intact after applying it to the surface
Fe3O4 nanoparticles.
The thermal stability of the COF@Fe3O4 was investi-
gated using TG curve (Figure 9). The TG analyses of the
sample demonstrate major weight loss in two steps.
The initial weight loss (of about 35%) from room temper-
ature to 350ꢀC is due to the decomposition of COF and
removal of the adsorbed water. A second weight loss
from 350 to 700 ꢀC is due to the decomposition of
3,4-dihydroxybenzaldehyde and other organic groups.
The magnetic properties of Fe3O4, Fe3O4@3,4-
dihydroxybenzaldehyde, and COF@Fe3O4 NPs were
measured by vibrating a sample magnetometer at room
temperature (Figure 10). The saturation magnetization of
bare Fe3O4 was found to be 49.8 emu/g. There
FIGURE 6 EDS spectrum of COF@Fe3O4
was
a
slight decrease in the magnetization of
Fe3O4@3,4-dihydroxybenzaldehyde and COF@Fe3O4,
namely, 29.6 and 19.1 emu/g, which can be attributed to
the grafting of 3,4-dihydroxybenzaldehyde and COF,
respectively.
The Brunauer–Emmett–Teller (BET) surface area,
pore volume, and the pore radius of COF@Fe3O4 are
depicted in Scheme 2. For COF@Fe3O4, the BET surface
area, pore volume, and pore diameter was 41.11 m2/g,
0.18 cm3/g, 18.4 nm, respectively.
FIGURE 7 XRD spectra of the COF@Fe3O4
To evaluate the catalytic activity of COF@Fe3O4 com-
posites, a one-pot three-component reaction of benzil
(1.0 mmol), benzaldehyde (1.0 mmol), and ammonium
acetate (3.0 mmol) in the presence of COF@Fe3O4 as a
catalyst in PEG 200 (2.0 mL) was selected as a model to
find out the optimal conditions, and the results are sum-
marized in Table 1. Control experiments indicated that
the model reaction in PEG 200 without a catalyst at room
temperature provided a negligible yield. However, the
same reaction with COF@Fe3O4 (30 mg) in PEG 200 was
XRD measurements were carried out to determine
the crystalline structure of the synthesized COF@Fe3O4
nanocomposites is shown in Figure 7. The XRD pattern
of COF@Fe3O4 indicates representative peaks with low
intensity, matching the standard Fe3O4 sample. The
broad peaks between 20ꢀ and 30ꢀ were due to the
amorphous COF phase in the COF-coated Fe3O4

6 of 13
AZIZI ET AL.
FIGURE 8 SEM images of
COF@Fe3O4
FIGURE 9 TG of COF@Fe3O4
remarkably improved the yield of the desired imidazole.
The one-pot reaction was carried out in various polar and
nonpolar organic solvents (entries 1–18). The low results
due to the insufficient catalyst activity levels were
obtained in nonpolar and aprotic polar organic solvents.
Although most of the polar solvents such as methanol,
ethanol, and glycerol displayed comparable activity, the
yield was increased in PEG 200 and gave the
FIGURE 10 Magnetization curves of (a) COF@Fe3O4,
(b) Fe3O4@3,4-dihydroxybenzaldehyde, and (c) Fe3O4
corresponding desired products in 95% of yield within
120 min (Table 1, entry 6). Furthermore, 30 mg of cata-
lyst gave the optimal results, and increasing the

AZIZI ET AL.
7 of 13
SCHEME 2 The BET curve of COF@Fe3O4
TABLE 1 Optimization of reaction conditions for
desired catalyst. The reaction could be monitored by
TLC, and in most cases, the solid products were detected
by simple visual assessment when the reaction was com-
pleted. It is imperative to note that the product can be
obtained with high purity through a simple separation
process without any harmful organic solvents—the addi-
tion of water and recrystallization in ethyl acetate or eth-
anol without further purification (Table 1).
2,4,5-trisubstituted imidazoles
Yields (%)a
The preliminary findings for the one-pot synthesis of
tri-substituted imidazole derivatives appear favorable by
using COF@Fe3O4 as the catalyst and PEG 200 as a sol-
vent; the scope and general applicability using different
aldehydes and benzil were further examined. The pursuit
of results in Table 2 shows that the COF@Fe3O4 catalyst
was an excellent activity with a wide range of aldehydes
and benzil derivatives, and in all cases, desired products
were obtained in good to excellent yields under mild con-
ditions. Aromatic aldehydes having both electron-
donating and electron-withdrawing groups such as
bromo, chloro, hydroxy, methoxy, methyl, nitro, and
ester were applied using optimized reaction conditions.
The reactions of all tested aldehydes with benzil,
irrespective of their electronic nature, proceeded very
well in satisfactory yields. However, aldehydes bearing
electron-withdrawing groups were identified to react
more rapidly than their electron-rich or neutral system.
2-Furaldehyde and 4-pyridinecarbaldehyde as the acid-
sensitive heterocyclic aldehydes were also viable sub-
strates and provided the desired imidazoles in good
yields. Next, reactions of aldehyde derivatives with
substituted benzil were investigated. Both electron-rich
and electron-deficient benzils are appropriate substrates
for this reaction to produce the corresponding imidazole
in good chemical yields.
Entry
1
COF@Fe3O4
Solvents (2 mL)
PEG
-
25
48
54
72
78
95
95
88
45
65
52
48
72
73
84
45
61
51
2
10
15
20
25
30
50
30
30
30
30
30
30
30
30
30
30
30
PEG
3
PEG
4
PEG
5
PEG
6
PEG
7
PEG
8b
9c
10
11
12
13
14
15
16
17
18
PEG
PEG
THF
Ethanol
neat
CH3CN
Methanol
Glycerin
n-Hexane
CH2Cl2
Water
aIsolated yields.
bCOF as a catalyst.
cFe3O4 as a catalyst.
One-pot four-component synthesis of 1,2,4,5-
substituted imidazoles was evaluated to broaden the syn-
thetic strategy's generality and efficiency. Initially, the
model reaction was performed using benzil (1.0 mmol),
ammonium acetate (1.2 mmol), benzaldehyde (1.0 mmol),
and aniline (1.0 mmol) in the presence of COF@Fe3O4
catalysts in PEG-200 (2.0 ml). Notably, the same reaction
was not successful, and tetra-substituted imidazoles were
COF@Fe3O4 (30 mg) to 50 mg did not affect the reaction.
The use of smaller amounts of COF@Fe3O4 (10 mg) lon-
ger reaction time (8 h) was required to reach the optimal
yields (Table 1, entry 1). Using COF (Table 1, entry 7)
and Fe3O4 (Table 1, entry 8) alone as a catalyst for the
model reaction suggests that the COF played an essential
catalytic role and the Fe3O4 improved isolation of the

8 of 13
AZIZI ET AL.
TABLE 2 Various kind of prepared 2,4,5-trisubstituted imidazoles derivatives under the mild reaction conditiona
aIsolated yields.
not observed even after stirring at room temperature for
24 h in PEG. After the extensive screening of the model
reaction, the best yield was achieved using 30 mg of
catalyst at 80ꢀC, which provided the corresponding
tetrasubstituted imidazole in 92% yield within 4 h.
Various structurally diverse amines and aromatic
aldehydes were reacted in model reaction to explore the
present method's scope and generality. A wide range of
aromatic aldehydes reacts cleanly with various alkyl, aryl
and heteroaryl amines, ammonium acetate, and benzil
under optimized conditions to provide the corresponding
substituted imidazole derivatives in good to excellent
yields. The results are presented in Table 3. All the
aromatic amines displayed good reactivity, and aromatic
amines with electron-donating groups showed higher
activity than their electron-withdrawing counterparts.
(Table 3, 5j–5n). Moderate and good yields were also
found for different aliphatic amines and heteroaryl
amines, respectively (Table 3, 5o–5t). All aryl
aldehydes were the right partner, and the aldehydes'
electronic nature does not affect the yield and reaction
conditions.
The effectiveness of the present protocol was further
showcased for the synthesis of Paal–Knorr pyrrole via the
reaction between aniline and 2,5-hexanedione in
the presence of COF@Fe3O4 as an efficient catalyst to
provide access to an N-substituted pyrrole (Table 4).
Initial optimization studies were carried out by treating
aniline (1.0 mmol) with 2,5-hexanedione (1.0 mmol) in
the presence of COF@Fe3O4 (30 mg) under various
conditions. Our investigation revealed that using
COF@Fe3O4 (30 mg) as the catalyst, the starting mate-
rials were entirely consumed after 180 min at room tem-
perature under solvent-free conditions. After completion
of the reaction (TLC and GC–MS monitoring, and in
some cases, the reaction mixtures began to solidify at the
end of the reaction), ethyl acetate was added, and the
magnetic catalyst was removed by an external magnet;
the product recrystallized from a mixture of ethyl acetate
and Petroleum ether (1:10) to yield the pure product in
quantities yield (Table 4, 7a). The generality and scope of
the reaction were investigated by varying the substituents
on the amine partners indicating the excellent substrate
tolerance of the composite catalyst in pyrrole synthesis

AZIZI ET AL.
9 of 13
TABLE 3 Various kind of prepared 1,2,4,5-substituted imidazoles derivatives under the mild reaction condition
(Table 4). As revealed in Table 4, electron-donating and
electron-withdrawing groups on the aryl amines did not
significantly deter the yields, and most of the reactions
performed efficiently under the optimal conditions. How-
ever, anilines bearing electron-donating groups required
a shorter time than electron-withdrawing groups and
gave higher yields. Benzylic amine and aliphatic amines
were slightly less reactive than aromatic counterparts
gave the corresponding pyrrole derivatives in moderate
yields (Table 4).
The recycling stability and the lifetime of a heteroge-
neous catalyst are of great importance for its industrial
application. Another vital feature of COF@Fe3O4 as a
heterogeneous magnetic catalyst is easily and rapidly sep-
aration using an external magnetic field after the reac-
tion. The recycling of COF@Fe3O4 was studied using the
synthesis of N-aryl pyrrole 7a under optimized
conditions. At the end of the reaction, the mixture was
diluted with ethanol (10 ml). The magnetic catalyst was
separated by employing an external magnetic field,
washed with ethanol and ethyl acetate, and dried at 60ꢀC
under vacuum. It was reused in the model reaction at
least five times with only a neglect decrease in inactivity
(Figure 11). The EDS and elemental analysis of the
reused catalyst after 5 cycles did not change the
nanocomposite morphology (Figure 12). The excellent
iteration of the COF@Fe3O4 nanocomposites due to the
covalent attachment of COF and magnetic nanoparticle
indicates a stable and durable catalyst.
The plausible mechanism of the magnetic COF cata-
lyzed the synthesis of tetraaryl substituted imidazole is
illustrated in Figure 13. First, covalent organic frame-
works were activated the carbonyl group of aldehyde and
facilitate the formation of the imine intermediate

10 of 13
AZIZI ET AL.
TABLE 4 COF@Fe3O4 catalyzed environmentally synthesis of pyrrole derivatives
FIGURE 11 Recycling results of the COF@Fe3O4 in the
synthesis of pyrrole
FIGURE 12 EDS spectrum of reused COF@Fe3O4
between ammonia and aldehyde by eliminating a water
molecule. The aromatic amine in the reaction mixture
further reacts with the imine intermediate to produce an
aminal type intermediate. Finally, condensation reaction
of aminal with benzil made cyclic imino intermediate
through dehydration with the assist of COF and gave the
desired imidazole derivatives.
The proposed mechanism of the magnetic COF cata-
lyzed the synthesis of N-aryl pyrrole is illustrated in
Figure 14. At first, the carbonyl group of 2,5-hexanedione
is activated by magnetic COF and susceptible carbonyl
group to a condensation reaction with amines. Then, the
nucleophilic addition of amine gave a cyclic hemiaminal
intermediate that dehydrated to N-aryl pyrrole.
As a final point, a comparison of our novel and green
COF@Fe3O4-catalyzed procedure and other literature for
the synthesis of pyrrole derivatives via condensation reac-
tion of amine and 2,5-hexanedione is presented in
Table 5. The comparison study clearly demonstrates the
excellent applicability of the COF@Fe3O4 in terms of
yield, economical, eco-friendly, reusability, and simple
work-up compared with the reported methods.

AZIZI ET AL.
11 of 13
FIGURE 13 Proposed mechanism for the
magnetic COF catalyzed the tetraaryl
substituted imidazole
FIGURE 14 Proposed mechanism for the magnetic COF catalyzed pyrrole synthesis
TABLE 5 Comparison of the literatures
Entry
Catalyst
Reaction conditions
CH2Cl2, 90ꢀC, 60 min
DMSO,100ꢀC, 180 min
Water, 60ꢀC, 240 min
DMSO, 20ꢀC, 120 min
Water,60ꢀC, 120 min
US, r.t, 90 min
Reusability of system
Yield %
97
References
Cho et al.[39]
Ivanova et al.[44]
Azizi et al.[40]
Azizi et al.[40]
Azizi et al.[40]
Zhang et al.[43]
Azizi et al.[40]
De[41]
1
2
3
4
5
6
7
8
Montmorillonite K-10
Yes
No
No
No
No
No
No
No
KOH
63
Squaric acid
CuI
90
88
FeCl3
95
BiCl3
90
ZrOCl2
KSF
US, r.t, 90 min
95
Neat, r.t, 400 min
95
(Continues)

12 of 13
AZIZI ET AL.
TABLE 5 (Continued)
Entry
9
Catalyst
Bi (NO3)3
RuCl3
Reaction conditions
Neat, r.t, 600 min
Neat, r.t, 60 min
US, r.t, 45 min
Reusability of system
Yield %
96
References
De[41]
De[41]
Zhang et al.[43]
Zhang et al.[43]
Shaibuna et al.[42]
Wang et al.[45]
Schirmacher et al.[46]
This work
No
10
No
96
11
LaCl3
No
90
12
ZrCl4
US, r.t, 7 min
Yes
Yes
Yes
Yes
Yes
98
13
ZrCl2
DES, 10 min
92
14
Ionic liquid
HFIP
Ionic liquid, r.t, 180 min
Reflux, 25 min
95
15
90
16
COF@Fe3O4
Neat, r.t, 120 min
97
ORCID
4 | CONCLUSION
Najmedin Azizi https://orcid.org/0000-0002-1685-038X
Fatemeh Heidarzadeh https://orcid.org/0000-0002-
9662-6344
In summary, novel COF@Fe3O4 nanocomposites were
constructed with a combination of surface-modified mag-
netic nanoparticle, and covalent organic frameworks
prepared in situ via a facile hydrothermal method. The
as-synthesized COF@Fe3O4 was employed as an effective
and reusable heterogeneous catalyst for rapid synthesis of
imidazole and pyrrole derivatives in environmentally
benign solvents under mild conditions. This procedure's
outstanding advantages are excellent catalytic perfor-
mance, mild reaction conditions, non-toxic, short reac-
tion time, good to excellent yields, and simple work-up.
The recovery of COF@Fe3O4 using an external magnet
with a minimal loss of catalytic was a simplified work-up
and purification process.
Fezeh Farzaneh https://orcid.org/0000-0003-4095-8101
REFERENCES
[1] K. Geng, T. He, R. Liu, S. Dalapati, K. T. Tan, Z. Li, S. Tao, Y.
Gong, Q. Jiang, D. Jiang, Chem. Rev. 2020, 120, 8814.
[2] S. Y. Ding, W. Wang, Chem. Soc. Rev. 2013, 42, 548.
[3] S. Y. Ding, J. Gao, Q. Wang, Y. Zhang, W. G. Song, C. Y. Su,
W. Wang, Chem. Soc. 2011, 133, 19816.
[4] F. Zhao, H. Liu, S. D. Mathe, A. Dong, J. Zhang,
Nanomaterials 2018, 8, 15.
[5] L. Huang, N. Mao, Q. Yan, D. Zhang, Q. Shuai, ACS Appl.
Nano Mater. 2019, 3, 319.
[6] J. Yang, Y. Zhu, M. Fan, X. Sun, W. D. Wang, Z. Dong,
J. Colloid Interface Sci. 2019, 554, 157.
[7] D. Xu, Z. K. Cui, J. Yang, M. Yuan, X. L. Cui, X. Y. Zhang, Z.
Dong, Int. J. Hydrogen Energy 2017, 42, 27034.
ACKNOWLEDGEMENT
Financial support of this work by Iran National Science
Foundation (INSF, grant number: 98015375) is gratefully
appreciated.
[8] C. Gao, J. Bai, Y. He, Q. Zheng, W. Ma, Z. Lei, M. Zhang, J.
Wu, F. Fu, Z. Lin, ACS Appl. Mater. Interfaces 2019, 11, 13735.
[9] P. J. Waller, S. J. Lyle, T. M. Osborn Popp, C. S. Diercks, J. A.
Reimer, O. M. Yaghi, J. Am. Chem. Soc. 2016, 138, 15519.
[10] A. R. Sardarian, I. Dindarloo Inaloo, M. Zangiabadi, New
J. Chem. 2019, 43, 8557.
[11] I. Dindarloo Inaloo, S. Majnooni, H. Eslahi, M. Esmaeilpour,
Mol. Catal. 2020, 492, 110915.
[12] I. Dindarloo Inaloo, S. Majnooni, H. Eslahi, M. Esmaeilpour,
New J. Chem. 2020, 44, 13266.
AUTHOR CONTRIBUTIONS
Najmedin Azizi: Supervision; conceptualization; meth-
odology; writing-review and editing. Fatemeh
Heidarzadeh: Formal analysis; methodology; software;
writing-original draft. Fezeh Farzaneh: Investigation;
methodology; formal analysis.
[13] I. Dindarloo Inaloo, M. Esmaeilpour, S. Majnooni, A. R.
Oveisi, ChemCatChem 2020, 12, 5486.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are avail-
able from the corresponding author upon reasonable
request.
[14] H. Singh, J. K. Rajput, Appl. Organomet. Chem. 2018, 32,
E3989.
[15] Y. Zhu, W. D. Wang, X. Sun, M. Fan, X. Hu, Z. Dong, ACS
Appl. Mater. Interfaces 2020, 12, 7285.

AZIZI ET AL.
13 of 13
[16] D. Jiang, Chem 2020, 6, 2461.
[17] H. Zhao, G. Yu, M. Yuan, J. Yang, D. Xu, Z. Dong, Nanoscale
2018, 10, 21466.
[36] G. Patel, A. R. Patel, S. Banerjee, New J. Chem. 2020, 44,
13295.
[37] N. Vala, P. Joshi, M. Mishra, New J. Chem. 2020, 44, 8859.
[38] T. Solimani Ahooie, N. Azizi, I. Yavari, M. M. Hashemi,
J. Iran. Chem. Soc. 2018, 15, 855.
[39] H. Cho, F. Toeroek, B. Toeroek, Green Chem. 2014, 16, 3623.
[40] N. Azizi, A. Khajeh-Amiri, H. Ghafuri, M. Bolourtchian, M. R.
Saidi, Synlett 2009, 14, 2245.
[18] L. Zhai, W. Wei, B. Ma, W. Ye, J. Wang, W. Chen, X. Yang, S.
Cui, Z. Wu, C. Soutis, G. Zhu, ACS Mater Lett. 2020, 2, 1691.
[19] Y. Qian, D. Li, Y. Han, H. L. Jiang, J. Am. Chem. Soc. 2020,
142, 20763.
[20] T. J. Peglow, G. P. Costa, L. F. Duarte, M. S. Silva, T. Barcellos,
G. Perin, D. Alves, J. Org. Chem. 2019, 84, 5471.
[21] J. G. Lombardino, E. H. Wiseman, J. Med. Chem. 1974, 17,
1182.
[41] S. K. De, Catal. Lett. 2008, 124, 174.
[42] M. Shaibuna, L. V. Theresa, K. Sreekumar, Catal. Lett. 2018,
148, 2359.
[22] Y. Gu, R. De Sousa, G. Frapper, C. Bachmann, J. Barrault, F.
Jérôme, Green Chem. 2009, 11, 1968.
[43] Z. H. Zhang, J. J. Li, T. S. Li, Ultrason. Sonochem. 2008,
15, 673.
[23] R. J. Sundberg, R. B. Martin, Chem. Rev. 1974, 74, 471.
[24] T. N. Doman, S. L. McGovern, B. J. Witherbee, T. P. Kasten, R.
Kurumbail, W. C. Stallings, D. T. Connolly, B. K. Shoichet,
J. Med. Chem. 2002, 45, 2213.
[44] E. V. Ivanova, E. Y. Schmidt, N. V. Semenova, B. A. Trofimov,
I. A. Ushakov, Mendeleev Commun. 2020, 30, 315.
[45] B. Wang, Y. Gu, C. Luo, T. Yang, L. Yang, J. Suo, Tetrahedron
Lett. 2004, 45, 3417.
[25] N. Azizi, N. Dado, A. K. Amiri, Can. J. Chem. 2012, 90, 195.
[26] S. Kamijo, Y. Yamamoto, Chem. – Asian J. 2007, 2, 568.
[27] T. Song, Z. Ma, P. Ren, Y. Yuan, J. Xiao, Y. Yang, ACS Catal.
2020, 10, 4617.
[46] R. H. E. Schirmacher, D. Rösch, F. Thomas, Tetrahedron 2021,
83, 131985.
[47] N. Aziizi, Z. Manochehri, A. Nahay, S. Torkashvand, J. Mol.
Liq. 2014, 196, 153.
[28] J. Jayram, V. Jeena, RSC Adv. 2018, 8, 37557.
[29] B. Das, C. Sudhakar, Y. Srinivas, Synth. Commun. 2010, 40,
2667.
[30] S. N. Murthy, B. Madhav, Y. V. Nageswar, Tetrahedron Lett.
2010, 51, 5252.
[48] N. Azizi, S. Dezfooli, M. M. Hashemi, C. R. Chimie 2013,
16, 997.
[49] F. Yazdani, B. Fattahi, N. Azizi, J. Magn. Magn. Mater. 2016,
406, 207.
[31] M. Kidwai, P. Mothsra, Tetrahedron Lett. 2006, 47, 5029.
ꢀ
[32] N. Higuera, D. Peña-Solorzano, C. Ochoa-Puentes, Synlett
How to cite this article: N. Azizi,
F. Heidarzadeh, F. Farzaneh, Appl Organomet
Chem 2021, e6373. https://doi.org/10.1002/aoc.
6373
2019, 30, 225.
[33] K. Sivakumar, A. Kathirvel, A. Lalitha, Tetrahedron Lett. 2010,
51, 3018.
[34] C. Y. Chen, W. P. Hu, P. C. Yan, G. C. Senadi, J. J. Wang, Org.
Lett. 2013, 15, 6116.
[35] S. Yugandar, S. Konda, G. Parameshwarappa, H. Ila, J. Org.
Chem. 2016, 81, 5606.