Magnetic mesoporous poly-melamine–formaldehyde: an efficient and recyclable catalyst for straightforward one-pot synthesis of imidazo[1,2-a]pyridines

Article abstract of DOI:10.1007/s13738-019-01705-3

Abstract: Magnetically separable mesoporous poly-melamine–formaldehyde nanocomposite (Fe₃O₄@mPMF) has been synthesized and characterized by FTIR spectroscopy, SEM, XRD spectroscopy and EDS. The magnetically separable Fe₃O<

Full text of DOI:10.1007/s13738-019-01705-3

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-019-01705-3
ORIGINAL PAPER
Magnetic mesoporous poly‑melamine–formaldehyde: an efcient
and recyclable catalyst for straightforward one‑pot synthesis
of imidazo[1,2‑a]pyridines
Mohammad Heydari1 · Najmedin Azizi2 · Zohreh Mirjafari1 · Mohammad Mahmoudi Hashemi1
Received: 1 February 2019 / Accepted: 3 June 2019
© Iranian Chemical Society 2019
Abstract
Magnetically separable mesoporous poly-melamine–formaldehyde nanocomposite (Fe3O4@mPMF) has been synthesized and
characterized by FTIR spectroscopy, SEM, XRD spectroscopy and EDS. The magnetically separable Fe3O4@mPMF catalyst
had excellent efciency for the synthesis a wide diversity of imidazo[1,2-a]pyridines by a three-component reaction of a
2-aminopyridine, aldehyde and isocyanide in good-to-excellent yields within a short reaction time, through an environmental
friendliness and straightforward procedure. The nanocomposite that is easily recoverable and also found to be reusable can
be recovered and reused when the reaction is completed for several times without distinct deterioration in catalytic activity.
Graphic abstract
Keywords Fe3O4@mPMF · Groebke reaction · Imidazo[1,2-a]pyridines · Green chemistry · Isocyanide reaction
Introduction
aspects has been an active topic in the feld of modern
organic chemistry [1, 2]. One approach to address this chal-
lenge involves the development of any operationally sim-
ple, green and practical multicomponent reactions (MCRs)
[3–11]. Among the known MCRs, those based upon the
reactivity of isocyanides play a pivotal role in organic syn-
thesis for their capacity to provide complex products from
simple reactants [12–23]. Due to the high biological activ-
ity of therapeutically relevant fused imidazoles bridge-
head nitrogen heterocyclic in a number of biologically or
pharmacologically important compounds, various meth-
ods have been reported for their synthesis via multicom-
ponent reactions [24–27]. Among the reported methods,
The development of simple and low-cost protocols to
improve the preparation of important heterocyclic com-
pounds while combining economic and environmental
* Najmedin Azizi
azizi@ccerci.ac.ir
1
Department of Chemistry, Science and Research Branch,
Islamic Azad University, Tehran, Iran
2
Chemistry and Chemical Engineering Research Center
of Iran, P.O. Box 14335-186, Tehran, Iran
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
three-component isocyanide-based reactions starting from
2-aminoazine, aldehydes and isocyanides catalyzed by
Lewis or Bronsted acids as well as ionic liquid are common
strategies [28–36].
dimethyl sulfoxide (DMSO) in a 25 mL Tefon container
secured in a steel reactor. The reaction mixture was heated
to 120 °C in an oven for 2 h. The reactor was then carefully
removed from the oven for stirring on a magnetic stirrer
plate to obtain a homogeneous solution. It was then heated to
170 °C in the oven for 72 h. The reaction was allowed to cool
to room temperature, and the obtained solid was crushed,
fltered and washed with acetone, ethyl acetate and CH2Cl2.
The resulting solid was dried under vacuum at 80 °C for
24 h (Scheme 1).
Traditional homogenous catalysts consumed in large
amounts for a range of products in chemistry, pharmacy,
food, favor and coatings sectors were the main sources of
pollution [37, 38]. On the other hand, magnetically sepa-
rable nanostructured catalysts showing the enhanced and
sustainable properties is receiving increasing attention as
an alternative reaction media that circumvent the problems
associated with many of the traditional catalysts [39, 40].
Porous organic polymers have recently attracted huge
research interest due to the regular pore structure and high
surface area, thereby proving potential applications in areas
of energy and environmental research, catalyst and supports
supercapacitors [41, 42]. Mesoporous poly-melamine–for-
maldehyde (mPMF) polymer is an interesting catalyst in the
context of green chemistry due to their unique properties,
such as a high surface area, good porosity and high density
of amine and triazine groups [43, 44]. In addition, by incor-
porating a functional group to the mPMF, it was possible to
make functional polymer, that provides more active reac-
tion sites, which was favorable for the catalytic applications
[45–49]. However, pure mPMF has usually some shortcom-
ings including a light density, low specifc surface area, and
difcult to separate from the reaction mixture leading to a
fair obstacle in its applications. Therefore, it is necessary to
solve the above-mentioned issues, and coupling with mag-
netic Fe3O4 nanoparticle is a feasible route and may ofer
a convenient solution to catalytic recycling problem [49].
General procedure
A test tube, equipped with a magnetic stir bar, 2-amino-
pyridine (0.2 mmol), benzaldehyde (0.2 mmol), cyclohexyl
isocyanide (0.2 mmol) and magnetic mPMF(10 mg), was
added in EtOH (1 mL), respectively, and the resulting mix-
ture was stirred at 60 °C until the reaction was complete.
After completion of the reaction controlled by TLC, the
crude product was concentrated under reduced pressure,
and the solid residue was crystallized from ethyl acetate.
All synthesized compounds are known and were character-
ized by melting points found to be identical with the ones
described in literature. white powder, mp=176–178 °C, 1H
NMR (500 MHz, CDCl3): δ = 1.22 (s, 3H, CH), 1.34 (d,
J = 10 Hz, 2H, CH), 1.63 (s, 3H, CH), 1.69 (m, 2H, CH),
1.74 (d, J=Hz, 2H, CH), 2.98–3.01 (m, 1H, CH), 4.18–4.21
(br s, 1H, CH), 7.17 (m, 1H, H), 7.39–7.42 (m, 1H, CH),
7.46–7.50 (m, 3H, Ar–H), 8.17 (d, 2H, Ar–H) 8.21 (m, 1H,
Ar–H), 8.44 (d, J=5 Hz, 1H, Ar–H).
Results and discussion
Experimental
This project is a part of our ongoing efort to develop green
chemistry toward several multicomponent reactions for the
synthesis of fused heterocycle compounds [50–53]. In con-
tinuation of this project, we now report a one-pot synthesis
of 3-aminoimidazo-fused heterocycles by a three-component
reaction of 2-aminopyridine, aldehyde and isocyanide in the
presence of magnetic mPMF as a promising recycle catalyst.
Magnetic mPMF was synthesized from the melamine pre-
cursors according to previous literatures [40]. Hydrothermal
reaction of the melamine and paraformaldehydes in the pres-
ence of Fe3O4 produces the requisite magnetic mPMF in a
simpler manner (Scheme 1).
General
All chemicals such as aldehydes, isocyanide, amine, Fe3O4,
melamine and paraformaldehydes were commercially avail-
able. Melting points were determined on Buchi 535 melt-
1
ing point apparatus. H NMR spectra were recorded on
500 MHz NMR spectrometer using DMSO-d6 as solvent.
Solvents were distilled before use. FTIR spectra were deter-
mined on a Bruker Vector-22 infrared spectrometer using
KBr disks.
Preparation of magnetic mesoporous
poly‑melamine–formaldehyde
The morphology and structure of the Fe3O4@mPMF
were investigated by SEM, FTIR spectroscopy, XRD
spectroscopy and EDX spectroscopy. The FTIR spec-
tra exhibit the patterns of a high density of triazine and
aminal (–NH–CH2–NH–) functional groups present in
Fe3O4@mPMF that are shown in Fig. 1. FTIR spectrum
of shows broad peaks associated with –NH-stretching and
The magnetic Fe3O4 nanoparticle was synthesized using a
modifed method reported in the literature [43]. Melamine
(0.378 g, 3 mmol), paraformaldehyde (1.8 eq. 0.162 g,
5.4 mmol) and Fe3O4 (0.2 g) were mixed with 3.36 mL of
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Journal of the Iranian Chemical Society
Scheme 1 Synthesis of magnetic mPMF
Fig. 1 FTIR spectra of Fe3O4@mPMF
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Journal of the Iranian Chemical Society
physisorbed water molecules at 3429 cm−1 together with
the band at 2998 cm−1 (CH2 stretching). Other characteris-
tic peaks around 1337 cm−1 indicate that the triazine units
are efciently incorporated in PMF sample. The charac-
teristic broad peak of Fe–O at 580–660 cm−1 is attributed
to the existence of Fe3O4 MNPs.
Scanning electron microscopy (SEM) revealed that
PMF formed a foam-like structure with interconnected
mesoporous networks (Fig. 3). After Fe3O4 nanoparticles
were introduced and grafted onto the surface of PMF, the
morphological properties of PMF keep intact.
The crystal structure of the of Fe3O4@mPMF was meas-
ured by XRD, and the results are shown in Fig. 4. The XRD
pattern of Fe3O4@mPMF shows characteristic peaks and
relative intensity, which match well with the standard Fe3O4
sample. The broad peak at 2θ of 27° and 45° are consistent
with an amorphous mPMF in the nanocomposite.
The chemical composition and percentage of Fe3O4@
mPMF were confrmed using energy-dispersive spectro-
scopic (EDS) analysis which clearly showed the presence
of C, N, Fe and O and confrmed that the Fe3O4 nano-
particles were successfully introduced onto the surface of
PMF (Fig. 2).
To explore the feasibility of Fe3O4@mPMF as recyclable
catalyst in the isocyanide-based multicomponent reaction,
Fig. 2 EDS spectra of Fe3O4@
mPMF
Fig. 3 FE-SEM images of Fe3O4@mPMF
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Journal of the Iranian Chemical Society
was complete within 120 min furnishing 4a in 94% yield
(Table 1, entry 8). The optimal amount of the Fe3O4@mPMF
was 20 mg, beyond which further increase in the amount of
the catalyst did not increase the yield appreciably. The infu-
ence of reaction temperature on yield was investigated. The
results show that 60 °C is sufcient to carry out reaction
in the optimum yield and increase in temperature further
does not enhance the yield. Additionally, the infuence of
various commercial aprotic and protic solvents like THF,
CH3CN, ethyl acetate, methanol and water on the reaction
yield was investigated and the results are given in Table 1
(entries 9–14). Control experiments performed using PMF
(Table 1, entry 6) and Fe3O4 (Table 1, entry 7) did not ofer
more than 94% of desired product.
Fig. 4 X-ray difraction pattern of Fe3O4@mPMF
Table 1 Optimization of reaction conditions
With the optimized reaction conditions, we extended our
studies to one-pot multicomponent reaction of various sub-
stituted aldehydes, 2-aminopyridine and cyclohexyl isocya-
nide in the presence of 20 mg of Fe3O4@mPMF using etha-
nol as solvent to evaluate the scope of this methodology, and
the results are presented in Table 2. As shown in Table 2,
this procedure represents an efcient and general access to
imidazo[1,2-a]pyridines derivatives with any kind of dif-
ferent functional group, and all the corresponding products
were obtained in good-to-excellent yields. The electronic
nature of the aldehydes had an infuence on the reaction
efciency and benzaldehydes with an electron-withdrawing
group on the aryl ring like nitro, bromo and chloro which
afforded the corresponding imidazo-[1,2-a]pyridines in
excellent yields and with shorter reaction times. For benza-
ldehydes bearing an electron-donating group such as methyl
and methoxy, the product was obtained in moderate yield
with longer reaction times. Interestingly, some heteroaryl
aldehydes also underwent the multicomponent reaction in
good yields.
Entry
Fe3O4@mPMF
(mg)
Solvent
Yields (%)a
1
2
3
4
5
10
15
20
20
20
20
40
20
20
20
20
20
20
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Water
Ethylacetate
CH3CN
THF
CH2Cl2
Methanol
62
74
81
94
48
90
25
94
68
70
74
46
75
94
5b
6c
7d
8
9
In addition, our green procedure was expanded from the
laboratory scale to the gram scale that is eco-friendly man-
ner for industrial preparation. The model reaction was car-
ried out in a 10 mL ethanol using 10 mmol of reactants in
the presence of 50 mg of Fe3O4@mPMF. After 200 min., 4a
was obtained in 90% yield.
10
11
12
13
14
aIsolated yields, broom temperature, cPMF as catalyst, dFe3O4 as cata-
lyst
An attractive feature of Fe3O4@mPMF as catalyst is being
facile, and rapid separation by using a magnet is highlighted
in Fig. 5. Further investigation involved the reusability of
the Fe3O4@mPMF for model reaction in the production of
4a under optimized conditions for 5 mmol scale (Table 2,
entry 1). Upon the completion of the reaction, Fe3O4@
mPMF was easily separated by using an external magnet.
The recovered Fe3O4@mPMF was washed with ethyl acetate
and dried under vacuum. The resultant residues were used
directly without further treatment for the next run after being
charged with fresh starting materials. Using this procedure,
Fe3O4@mPMF could be reused up to fve times without any
signifcant loss of the initial catalytic activity (Fig. 5). The
the reaction of benzaldehyde (1a), 2-aminopyridine (2) and
cyclohexyl isocyanide (3) was selected as a model to fnd
out the optimal reaction conditions and the results are men-
tioned in Table 1. In our initial experiments, we evaluated
various trial reactions in the model reaction. The experimen-
tal process could be easily achieved with simple operation
under mild reaction conditions. Our studies revealed that
imidazo[1,2-a]pyridin 4a was formed in excellent yields
(94%) in the presence of Fe3O4@mPMF, and the reaction
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Journal of the Iranian Chemical Society
Table 2 Various kinds of imidazo[1,2-a]pyridines derivatives in the optimized conditions
atomic absorption spectrometer (FAAS) analysis. After
compilation of reaction, Fe3O4@mPMF was magnetically
separated and the supernatant was analyzed in order to estab-
lish the leached quantity of total iron. The leaching of iron
was obtained below the detectable level.
Conclusion
In summary, novel Fe3O4@mPMF were synthesized and
investigated as a non-toxic and reusable catalyst in the syn-
thesis of fused imidazoles bridgehead nitrogen heterocyclic
compounds from the Ugi-type isocyanide-based multicom-
ponent reaction in a clean and efcient manner. The mild
reaction conditions, good-to-excellent yields, short reaction
Fig. 5 Recycling results of the Fe3O4@mPMF
FTIR spectrum of recovered Fe3O4@mPMF suggested no
signifcant change in functionality. Furthermore, recycled
sample was prepared for the Fe3O4 leaching study by fame
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Journal of the Iranian Chemical Society
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