Green synthesis of aminocarbonyl compounds using a nanostructured heterogeneous catalyst under mild reaction conditions

Article abstract of DOI:10.1080/24701556.2019.1577258

The synthesis of aminocarbonyl derivatives as biologically active compounds by using polyethylene glycol (PEG-400)-SO₃H-coated Fe₂O₃ is reported. The heterogeneous nanocatalyst was prepared via in-situ co-precipitation met

Full text of DOI:10.1080/24701556.2019.1577258

Inorganic and Nano-Metal Chemistry
ISSN: 2470-1556 (Print) 2470-1564 (Online) Journal homepage: https://www.tandfonline.com/loi/lsrt21
Green synthesis of aminocarbonyl compounds
using a nanostructured heterogeneous catalyst
under mild reaction conditions
Ali Maleki & Razieh Firouzi-Haji
To cite this article: Ali Maleki & Razieh Firouzi-Haji (2019): Green synthesis of aminocarbonyl
compounds using a nanostructured heterogeneous catalyst under mild reaction conditions,
Inorganic and Nano-Metal Chemistry, DOI: 10.1080/24701556.2019.1577258
To link to this article: https://doi.org/10.1080/24701556.2019.1577258
Published online: 20 Jun 2019.
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INORGANIC AND NANO-METAL CHEMISTRY
https://doi.org/10.1080/24701556.2019.1577258
Green synthesis of aminocarbonyl compounds using a nanostructured
heterogeneous catalyst under mild reaction conditions
Ali Maleki
and Razieh Firouzi-Haji
Catalysts and Organic Synthesis Research Laboratory Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 8 March 2017
Accepted 2 January 2019
The synthesis of aminocarbonyl derivatives as biologically active compounds by using polyethyl-
ene glycol (PEG-400)-SO3H-coated Fe2O3 is reported. The heterogeneous nanocatalyst was pre-
pared via in-situ co-precipitation method and its structure and morphology was characterized by
Fourier-transform infrared spectroscopy, energy-dispersive X-ray analysis, X-ray diffraction pattern,
field-emission scanning electron microscopy image, vibrating sample magnetometer curves, N2
adsorption-desorption isotherm and inductively-coupled plasma analysis. Noteworthy, the green
composite nanocatalyst was applied for the one-pot multicomponent synthesis of aminocarbonyl
compounds at room temperature. This work had advantages such as significant nanocatalyst activ-
ity, recoverability, short process time, mild reaction conditions and high products yields.
KEYWORDS
Heterogeneous nanocata-
lyst; nanocomposite;
magnetic nanoparticles;
polyethylene glycol (PEG-
400); aminocarbonyls
Introduction
According to green chemistry objective, the recovery and
reusability of catalysts is an important factor in the organic
synthetic reactions. Recently, magnetic nanoparticles (MNPs)
have received considerable attention in the field of green sus-
tainable catalysis due to easy preparation and functionaliza-
tion, high surface area, high dispersion, high reactivity and
easy separation due to their magnetic properties and nano-
scale size. Moreover, the immobilization of biocompatible
polymers onto the surface of (MNPs) such as Fe2O3 or Fe3O4
can provide a wide range of magnetic-functionalized catalyst
with higher activity, improved colloidal stability in physio-
logical media and low toxicity. Furthermore, these functional-
ized MNPs have emerged widely for organic synthesis.[3,4]
Poly(ethylene glycol) (PEG) as a biocompatible polyether
is widely used for coating nanoparticle’s surface.[5]
Immobilization of PEG onto the surface of nanoparticles
will enhance hydrophilicity and water-solubility of nanopar-
ticle surfaces and minimizes agglomeration. In the recent
years, several methods have been exploited for the modifica-
tion of PEG-based MNPs. It is found that most of them suf-
fer from some drawbacks such as complication and harsh
reaction conditions.[6] In this regard, the introduction of
new strategy for the synthesis of PEG-coated MNPs
is required.
Multicomponent reactions (MCRs) as an efficient and
powerful strategy in synthetic organic chemistry have
received considerable attention by organic chemists. MCRs
are reactions in which three or more starting materials react
together in one-pot conditions at the same time to synthe-
size the products. Noteworthy, most of the reactive atoms
were observed in the final products. They have several
advantages in terms of environmentally benign due to
reducing the number of synthetic steps, energy consumption
and waste production.[1]
Much attention has been paid to aminocarbonyl com-
pounds as an important class of N-containing heterocyclic
compounds due to their interesting biological activities.
Mannich reaction is the most known synthetic method
for the synthesis of these compounds, in which three
compounds under appropriate catalytic conditions brings
together to form the desired products. Recently, an increas-
ing interest has been focused on the synthesis of aminocar-
bonyl compounds due to their significant biological activity
and several methods have been reported in the literature for
the synthesis of these important nucleuses in the presence of
various catalysts. These methods, however, have a few draw-
backs such as toxic catalyst, longer reaction time and using
of expensive metal salt as catalyst. Moreover, the main dis-
advantage of some of them is that the catalysts are destroyed
and cannot be recovered and reused. Thus it is clearly
evident that the design and development of inexpensive,
general, and reusable catalysts in conjunction with multi-
component reactions strategy for the synthesis of aminocar-
bonyl compounds is of prime importance.[2]
In following of our previous work on green magnetically
recoverable nanocatalysts and our interest in one-pot
MCRs,[7–13] herein, we wish to report a facile MCR for the
synthesis of b-aminocarbonyl compounds 4a–l via the con-
densation of aniline 1, aldehyde 2 and ketone compound 3 in
the presence of PEG-SO3H-coated Fe2O3 as a superparamag-
netic heterogeneous nanocatalyst at room temperature in high
yields with rather short reaction times (Scheme 1).
CONTACT Ali Maleki
maleki@iust.ac.ir
Catalysts and Organic Synthesis Research Laboratory Department of Chemistry, Iran University of Science and
Technology, Tehran 16846-13114, Iran.
ß 2019 Taylor & Francis Group, LLC

2
A. MALEKI AND R. FIROUZI-HAJI
Scheme 1. Mannich-MCR for the synthesis of products 4a-l catalyzed by Fe2O3@PEG-SO3H.
Experimental
Results and discussion
Preparation of Fe2O3@PEG nanoparticles
Characterization of the prepared Fe2O3@PEG-SO3H
nanocatalyst
Fe2O3@PEG nanoparticles were prepared via in-situ co-pre-
cipitation method. Initially, 2.4 g of FeCl3 and 3.0 g of
FeCl2.5H2O was solved in 80 mL of deionized water. After
that, 30 mL of PEG-400 was mixed with 10 mL of NH3.H2O
Fe2O3@PEG-400-SO3H nanocatalyst was prepared by in situ
co-precipitation method. As can be seen in Figure S1, the
FT-IR spectrum of the Fe2O3@PEG-SO3H magnetic nanoca-
talyst can verify the preparation of the expected product. It
indicated that PEG was successfully composed onto the sur-
faces of Fe2O3 nanoparticles. The functionalization of SO3H
groups on Fe2O3@PEG-400 surface was also approved by
the predicted almost all of the absorption bands.
ꢀ
at 30 C in a three-necked flask. Then, the mixture of FeCl3
and FeCl2.5H2O was slowly added in NH3-PEG solution
ꢀ
during 130 min at 30 C. The obtained Fe2O3/PEG precipi-
tate was washed with deionized water until pH was reached
ꢀ
to 7. Finally, it was dried at 80 C in an oven.
Figure S2 shows the XRD measurements were performed
with the dried powder samples of bare and PEG coated
MNPs to identify the crystal phases present in the samples.
The XRD pattern of a representative Fe2O3@PEG-SO3H
(curve a) along with bare Fe2O3 NPs (curve b). The pattern
of the Fe2O3@PEG-SO3H showed all the major peaks corre-
sponding to Fe2O3. The diffraction angles (2h) of can be
assigned to appropriate planes, respectively; which are in
accordance with Fe2O3 reference pattern. Additionally, one
peak around 2h = 25ꢀ along with small peaks due to the
PEG-SO3H polymer are observed in the case of the
Fe2O3@PEG-400-SO3H. These results confirmed the surface
modification of the Fe2O3 NPs with PEG-SO3H.
The result of the EDX analysis of the Fe2O3@PEG-SO3H
magnetic nanoparticles was illustrated in Figure S3. It con-
firms the presence of carbon, oxygen and sulfur elements in
the nanocatalyst. Furthermore, inductively coupled plasma
(ICP) analyses of the catalysts revealed that the metal (Fe)
content of the catalyst ( 0.4%) were close to target metal
content (12 wt%).
Preparation of Fe2O3@PEG-SO3H nanoparticles
At first, a 500-mL suction flask was equipped with a con-
stant pressure dropping funnel. The gas outlet was con-
nected to a vacuum system through an adsorbing solution
of alkali trap. Fe2O3@PEG-400 (2.0 g) was added to the flask
and dispersed by an ultrasonic bath for 10 min in chloro-
form (50 mL). Then, a solution of chlorosulfonic acid (1
mL) in chloroform (2ꢀ0 mL) was added dropwise over a
period of 30 min at 0 C. After completion of the addition,
the mixture was shacked for 90 min, to remove residual
HCl. After that, Fe2O3@PEG-SO3H was separated from the
reaction mixture by a magnetic bar and washed several
times with dry chloroform. Finally, Fe2O3@PEG-SO3H was
ꢀ
dried under vacuum at 60 C.
To clarify the morphology of the nanocatalyst, FE-SEM
images of Fe2O3@PEG-SO3H were provided (Figures S4 in
supplementary materials). It can be seen that the nanocata-
lyst was uniformly prepared and the main structure of nano-
catalyst was rod-like morphology along with the spherical
iron oxide (II, III) nanoparticles. In addition, the nanosized
structure and morphology of the catalyst was proved by
FE-SEM images.
The magnetic properties of Fe2O3, Fe2O3@PEG and
Fe2O3@PEG-SO3H were measured by VSM curves at room
temperature. As can be seen in Figure S5, the hysteresis
loops of the superparamagnetic behavior can be clearly
observed for all the nanoparticles. The saturation magnetiza-
tion value of uncoated Fe2O3 MNPs, Fe2O3@PEG and
Fe2O3@PEG-SO3H confirmed the appropriate immobiliza-
tion of PEG and SO3H on the surface of the Fe2O3 NPs.
General procedure for the synthesis of aminocarbonyl
compounds 4a–l
Initially, a mixture of 2.0 mmol of aromatic aldehyde and
2.0 mmol of amine and 0.010 g of Fe2O3@PEG-400-SO3H
was added to 5 mL of absolute EtOH as a green solvent.
After that, the mixture was stirred at room temperature for
5-10 min until the starting materials had almost disappeared
(monitored by thin layer chromatograph, TLC). Then, 3.0
mmol of ketone was added to the mixture and the mixture
was stirred and the mixture was stirred for the appropriate
time until the completion of the reaction as monitored by
TLC. The catalyst was separated easily by an external mag-
net and reused as such for the next experiments. The prod-
ucts were isolated pure just by recrystallization from hot
EtOH and no more purification was needed.

INORGANIC AND NANO-METAL CHEMISTRY
3
Table 1. One-pot synthesis of the compounds 4a–l by using the magnetic
nanocatalyst.
ethanol, several solvents with different polarities were tested
using the model reaction in the presence Fe2O3@PEG-SO3H.
As it is obvious from the results, ethanol was the superior
solvent for this study than MeOH, H2O, MeCN, DMF, n-
hexane and ether in the presence of the nanocatalyst at
room temperature.
Finally, a comparison was done between the present work
and others earlier reports for the synthesis of 4d. The results
summarized in Table S2 clearly demonstrate the superiority
of the present work in saving energy, high yields of the
products and the reusability of the nanocatalyst.
In order to investigate the scope and limitations of
the present protocol and to show the application of
Fe2O3@PEG-SO3H in the synthesis of aminocarbonyl com-
pounds, a variety of products were synthesized under the
optimized conditions. The results summarized in Table 1
shows that all products were obtained in good-to-excellent
yields after appropriate reaction times.
The suggested possible mechanism for the formation of
aminocarbonyl compounds 4a-l is shown in Scheme 2. On
the basis of the literature and substrates chemistry, at first
step the amine 1 attacks to the activated aldehyde 2 in
the presence of Fe2O3@PEG-SO3H, to form iminium 5.
Moreover, the enol form of ketone 3 was formed via tauto-
merisation in the presence of the nanocatalyst. Finally, the
enol was added to 5 to yield the desired product 4.[14]
Mp (ꢀC)
Entry
R
Product Time (min) Yielda (%)
Found
Reported [14]
1
2
3
4
5
6
7
8
4-OMe
4-Br
4-Me
4-Cl
4a
4b
4c
4d
4e
4f
4g
4h
4i
45
25
50
25
50
30
30
25
30
40
45
50
80
92
65
95
72
80
87
90
78
80
85
65
147–148
127–128
131–132
116–117
170–171
126–128
141–142
94–95
147–149
127–129
130–132
116–119
169–170
125–127
140–142
95–96
H
3-OH
3-NO2
3-Br
3-OMe
2-NO2
2-Cl
9
106–107
160–161
50–52
106–107
158–162
52–53
10
11
12
4j
4k
4l
2-OMe
121–123
122–124
aIsolated yield.
The specific surface area of the prepared nanomaterial
was measured by using Brunauer–Emmett–Teller (BET) ana-
lysis with N2 adsorption-desorption. BET surface area of
Fe2O3@PEG-SO3H was about 45 m2
g
ꢁ1. The reduced
amount of surface area in comparison with iron oxide (II,
III) nanoparticles may be the consequence of immobilization
of PEG-OSO3H on Fe2O3 NPs.
Catalytic application of in the synthesis of
aminocarbonyl compounds 4a-l
Initially, to optimize the reaction conditions for the synthe-
sis of aminocarbonyl compounds, various parameters were
studied on the reaction aniline (2 mmol), 4-chlorobenzalde-
hyde (2 mmol) and acetophenone (3 mmol), as a pilot test.
First, the effect of the catalyst amount on the reaction yield
was studied. It was found that using 0.01 g of the
Fe2O3@PEG-SO3H nanocatalyst is sufficient to complete the
Recyclability of the nanocatalyst
The recoverability of Fe2O3@PEG-400-SO3H was studied in
the pilot experiment. After completion of the reaction, it
was separated by an external magnet and washed with
CH2Cl2, dried and reused in subsequent reactions. As can
reaction and give 4d after 25 min in 95% yield in 5 mL of be seen in Figure 1, the nanocatalyst can be reused at least
EtOH as a green solvent at room temperature. The results five times without any significant decrease in the products
summarized in Table S1. To compare the efficiency of yields. Additionally, after the nanocatalyst was reused five
Scheme 2. A proposed mechanism for the formation of aminocarbonyls using PEG-based magnetic nanocatalyst.

4
A. MALEKI AND R. FIROUZI-HAJI
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Figure 1. Recycling of the nanocatalyst in the synthesis of 4d.
times in the model reaction, to study the structure and
morphology of nanocatalyst, FT-IR spectroscopy (Figure S9
in supplementary material) and ICP analysis were taken
again. According to those analyses can be concluded that
structure of the nanocatalyst and the percentage of iron
loading was not significantly changed or leached.
Conclusions
In summary, a green, cost-effective, magnetic heterogeneous
nanocatalyst, Fe2O3@PEG-400-SO3H, was prepared through
a facile process and completely characterized by FT-IR, FE-
SEM, XRD, EDX, VSM, BET and ICP instrumental analyses.
Then, its catalytic performance was investigated in the syn-
thesis of aminocarbonyl compounds via Mannich MCR. The
products were obtained in high-to-excellent yields at room
temperature under simple reaction conditions. The green
nanocomposite catalyst was easily recovered by an external
magnet and reused efficiently several times without signifi-
cant decrease in its activity.
9. Maleki,
A.
One-pot
Three-component
Synthesis
of
Pyrido[20,10:2,3]imidazo[4,5-c]isoquinolines Using Fe3O4@SiO2–
OSO3H as an Efficient Heterogeneous Nanocatalyst. RSC Adv
2014, 4, 64169–64173. DOI:10.1039/C4RA10856F.
10. Maleki, A.; Azadegan, S. Preparation and Characterization of
Silica-supported Magnetic Nanocatalyst and Application in the
Synthesis of 2-amino-4 H -chromene-3-carbonitrile Derivatives.
Inorg. Nano-Met. Chem. 2017, 47, 917–924. DOI:10.1080/
24701556.2016.1241266.
11. Maleki,
A.;
Paydar,
R.
Graphene
Oxide–chitosan
Bionanocomposite: a Highly Efficient Nanocatalyst for the One-
pot Three-component Synthesis of Trisubstituted Imidazoles
under Solvent-free Conditions. RSC Adv. 2015, 5, 33177–33184.
DOI:10.1039/C5RA03355A.
Acknowledgements
The authors gratefully acknowledge the partial support from the
Research Council of the Iran University of Science and Technology
12. Maleki, A.; Zand, P.; Mohseni, Z. Fe 3 O 4 @PEG-SO 3 H Rod-
like Morphology along with the Spherical Nanoparticles: novel
Green Nanocomposite Design, preparation, characterization and
Catalytic Application. RSC Adv. 2016, 6, 110928–110934. DOI:
10.1039/C6RA24029A.
13. Maleki, A.; Zand, P.; Mohseni, Z. Green nanospheres natural
camphor coated ferrite as a highly efficient nanocatalyst for the
synthesis of dihydropyrimidine derivatives. Chem. Select. 2017, 2,
2740–2744.
ORCID
Ali Maleki
http://orcid.org/0000-0001-5490-3350
14. Maleki, A.; Zand, P.; Mohseni, Z.; Firouzi Haji, R. Green
Composite Nanostructure (Fe3O4@PEG-SO3H): Preparation,
characterization and Catalytic Performance in the Efficient
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