Cellulose matrix embedded copper decorated magnetic bionanocomposite as a green catalyst in the synthesis of dihydropyridines and polyhydroquinolines

Article abstract of DOI:10.1016/j.carbpol.2018.12.069

A new biopolymer-based magnetic nanocomposite was prepared and characterized by Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images,

Full text of DOI:10.1016/j.carbpol.2018.12.069

Accepted Manuscript
Title: Cellulose matrix embedded copper decorated magnetic
bionanocomposite as a green catalyst in the synthesis of
dihydropyridines and polyhydroquinolines
Authors: Ali Maleki, Vahid Eskandarpour, Jamal Rahimi,
Negar Hamidi
PII:
S0144-8617(18)31515-7
DOI:
Reference:
https://doi.org/10.1016/j.carbpol.2018.12.069
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Accepted date:
20 August 2018
2 December 2018
21 December 2018
Please cite this article as: Maleki A, Eskandarpour V, Rahimi J, Hamidi N, Cellulose
matrix embedded copper decorated magnetic bionanocomposite as a green catalyst in
the synthesis of dihydropyridines and polyhydroquinolines, Carbohydrate Polymers
(2018), https://doi.org/10.1016/j.carbpol.2018.12.069
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Cellulose matrix embedded copper decorated magnetic bionanocomposite as a
green catalyst in the synthesis of dihydropyridines and polyhydroquinolines
Ali Maleki,* Vahid Eskandarpour, Jamal Rahimi and Negar Hamidi
Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and
Technology, Tehran 16846-13114, Iran
* Corresponding author. Tel.: +98 21 77240540; fax: +98 21 73021584. E-mail address: maleki@iust.ac.ir (A. Maleki).
Graphical abstract
Highlights
 In-situ preparation and facile modification of a cellulose-based bimetallic nanocomposite.
 Efficient catalytic usage in two important one-pot organic condensation reactions in high yields
using simple and readily accessible precursors under solvent-free conditions at room temperature.
 Thermal stability and leaching-free character of the nanocatalyst during the organic reactions
enabled sustainability and reusability for several runs.
1

 Narrow size and uniform distribution of Cu and -Fe2O3 nanoparticles obtained on cellulose bio-
matrix in green bionanostructure.
 Short reaction times, simple work-up procedure, high atom economy, high yields and
environmentally-benign conditions.
Abstract
A new biopolymer-based magnetic nanocomposite was prepared and characterized by Fourier transform infrared (FT-IR) spectroscopy, energy-
dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images, inductively-
coupled plasma atomic emission spectroscopy (ICP-AES) analysis, thermogravimetric/differential thermal (TG/DT) analysis and atomic force
microscopy (AFM) image analysis. Then, it was applied as an efficient heterogeneous catalyst in two important three- and four-component
one-pot organic condensation reactions for the synthesis of Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives in high yields
under solvent-free condition at room temperature. The first design and development of a low-leaching bionanostructure, easy separation and
reusability of the nanocatalyst, simple work-up procedure, mild, green and environmentally friendly conditions are some important features
and advantages of the present work.
Keywords: Biopolymer; Cellulose; Green chemistry; Composite nanocatalyst; Dihydropyridine.
1. Introduction
Carbohydrate polymers due to their natural sources are one of the most interesting substrates for the nanocomposite synthesize
(Baran, Baran & Menteş, 2018; Baran, 2018). Cellulose is one of the most available natural polymers on the earth. It is a fibrous and
resistant biopolymer consists of monomers joined together by glycosidic oxygen bridges. The repeating unit of this natural polymer
is a dimer of glucose, known as cellobiose (Habibi, Lucia, & Rojas, 2010; Klemm et al., 2005). Various advantages of cellulose such
as biocompatibility, low toxicity and abundant resources make this polysaccharide as a perfect surface for catalyst preparation.
However, cellulose is not soluble in usual solvents and the need for new compounds and appropriate methods to increase the
solubility of these polymers should be considered. Forasmuch as, cellulose fibers also have some disadvantages such as moisture
absorption, quality variations, low thermal stability, and poor compatibility with the hydrophobic polymer matrix.
Due to the attractiveness of metal nanoparticles in applications such as electronics, optics materials, sensors, biomedicine and
catalytic applications. Synthesis of metal and metal oxide nanoparticles in the presence of stabilizing polymers have been intensively
developed in the recent years and natural polymers like cellulose due to the mentioned benefits are the best polymer for this purpose
and it can be used for biomedical applications (Baran, Baran & Menteş, 2018; Spiridonov et al., 2017). In addition to usual properties
of nanoparticles such as high activity level and easy preparation, magnetic nanoparticles are superior to other nanoparticles due to
their simple separation from the reaction mixture by an external magnet. The most important known magnetic nanoparticles are
Fe3O4 and -Fe2O3. FeO-Fe2O3 magnetite, tends to react with oxygen and finally forming non-magnetic oxide/hydroxide iron
compounds. Conversely, -Fe2O3 maghemite is chemically stable (Spiridonov et al., 2017)
Easy recovery of magnetic nanocomposites has made them an excellent choice for the catalysis of organic reactions. A technically
possible method for the recycling catalyst is immobilization of the catalytically-active species on the surface of magnetic metal
nanoparticles which can be separated from the reaction system by applying an appropriate magnetic field. Moreover, nanocomposites
of natural biopolymers have special significance, because of their environmentally-friendly behavior and green chemistry properties.
Multicomponent reactions (MCRs) are one-pot reactions in which three or more than three raw materials react with each other
to form a product incorporating essentially all of the starting materials (Zhu, & Bienaymé, 2005; Gunawan et al., 2012; Gunawan et al.,
2010; Dömling, Wang & Wang, 2012; Hulme, et al., 1998; Orru, & Greef, 2003). MCRs have opened a revolutionary option in the field
of designing methods to create chemical libraries of biologically active compounds (Zhu, & Bienaymé, 2005; Gunawan et al., 2012;
Gunawan et al., 2010; Dömling, Wang & Wang, 2012; Hulme, et al., 1998; Orru, & Greef, 2003).
Hantzsch 1,4-dihydropyridines were one of the first heterocyclic compounds that were synthesized via MCRs. They include
various medicinal, biological and pharmacological properties such as calcium channel blockers (David, 2007), antitumor (Boer, &
Gekeler, 1995), anti-inflammatory (Briukhanov, 1994; Bahekar, & Shinde, 2002) and analgesic (Gullapalli, & Ramarao, 2002) activities.
Today, several medicinally important drugs from these class compounds are used. For example: Amlodipine, Nimodipi, Diludine
2

and Felodipine are driven from these compounds (Bossert, Mayer, & Wehinger, 1981; Gilpin, & Pachla, 1999; Cosconati, et al., 2007
Fig. 1a).
Due to chemical and biological significance of 1,4-dihydropyridines and polyhydroquinolines, several methods have been
)
(
reported for the synthesis of their derivatives. The classical Hantzsch’s method for the synthesis of 1,4-dihydropyridines is a one-
pot condensation reaction of aldehydes with ethyl acetoacetate and ammonia under vigorous conditions (Love, & Snader, 1965). A
few methods have been developed to modify the reaction conditions. For instance: conventional heating (Sainani, & Shah, 1994;
Sufirez et al., 1999), solar thermal energy (Mekheimer, Hameed, & Sadek, 2008), ionic liquids (Ji et al., 2004; Zhang et al., 2006), metal
triflates (Wang et al., 2005; Donelson, Gibbs, & De, 2006), cerium(IV) ammonium nitrate (Reddy, & Raghu, 2008), silica perchloric acid
(Maheswara et al., 2006), microwave and ultrasound irradiations (Li et al., 2008; Tu et al., 2001) and Fe3O4 magnetic catalyst (Nasr-
Esfahani et al., 2014). But, most of them are suffering from various drawbacks such as harsh reaction conditions, expensive catalysts and
tedious work-up procedures. Therefore, design and development of new approches for this reaction is of prime importance.
In connection with our previous works on design and development of green protocols, nanocatalysts, biopolymer-based
nanocomposite and MCRs (Maleki, Jafari, & Yousefi, 2017; Maleki, Firouzi-Haji, & Hajizadeh, 2018; Maleki et al., 2018; Maleki, A &
Paydar, R, 2016; Maleki, & Sarvary, 2015; Maleki, Movahed, & Paydar, 2016; Maleki, Movahed, & Ravaghi, 2017), herein, we are hopefully
introducing a new cellulose-based nanocomposite and an efficient approach for the synthesis of 1,4-dihydropyridine and
polyhydroquinoline derivatives starting from simple and readily accessible of starting materials. Biopolymer-based bimetallic
bionanocomposite was prepared via in situ synthesis of maghemite (-Fe2O3) and immobilization of Cu on cellulose. We used this
novel nanocomposite for the synthesis of 1,4-dihyropyridines 5a-i and polyhydroquinolines 6a-s under solvent-free conditions at
room temperature. It showed superb catalytic activity in the organic synthesis (Fig. 1b).
3

Fig. 1. a) Some drugs containing 1,4-dihydropyridines cores, b) -Fe2O3/Cu@cellulose-catalyzed green synthesis of 5a-i and 6a-s.
4

2. Experimental
2.1. General
All solvents, chemicals and reagents were purchased from Merck, Fluka and Aldrich chemical companies. Melting points were measured on
an Electrothermal 9100 apparatus and are uncorrected. FT-IR spectra were recorded as KBr pellets on a Shimadzu FT-IR-8400S spectrometer.
Analytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254 Al-plates. NMR spectra were recorded on Bruker DRX-300 Avance
spectrometer. The morphology of the nanocatalyst was studied by scanning electron microscopy (SEM, Zeiss-Sigma VP) on gold coated
samples. TEM images were obtained on a Zeiss-EM10C-100KV instrument. EDX analysis was recorded on Numerix DXP-X10P. ICP-OES
were taken by Shimadzu ICPS-7000 model. TGA/DTA were measured by an STA504. The shell surface was mounted on the AFM stage and
the Triboscope recording unit with transducers and leveling device was placed on the top of a NanoScope III E 164 | 164 mm2 XY piezo scan
base.
2.2. Preparation of -Fe2O3/Cu@cellulose
A solution of NaOH, urea and H2O was prepared with material with the ratio of 7:12:81, respectively. Then, its temperature was cooled to -12
°C by ice and salt. 4.0 g of microcrystaline cellulose dissolved in it to form a homogeneous solution. Then, 0.5 g of FeCl2 and 1.0 g of FeCl3
were dissolved in 50 mL of deionized water was added dropwise into the cellulose mixture with vigorous stirring during 6 h. As a result, -
Fe2O3 nanoparticles were synthesized on cellulose fibers via in-situ co-precipitation method. The next step includes CuSO4.4H2O solution (1 g
CuSO4.4H2O dissolved in 20 mL H2O)adding dropwise to the mixture. Due to the presence of -Fe2O3 oxidizing nanoparticles, after the
addition of copper sulfate, Cu2+ can not be reduced to Cu. The final mixture was stirred for 2 h. Finally, the mixture was filtered and washed
with H2O (350 mL) and ethanol (350 mL) and dried at room temperature to yield the nanocomposite.
2.3. General procedure for the synthesis of 1,4-dihydropyridine derivatives 5a-i
A mixture of ethylacetoacetate (2.0 mmol), 4-chloro-benzaldehyde (1.0 mmol) and ammonium acetate (2.0 mmol) was vigorously stirred in a
5-mL round bottom flask in the presence of -Fe2O3/Cu@cellulose (3 mg) under solvent-free conditions at room temperature. The progress of
the reaction was monitored by TLC (ethyl acetate/n-hexane 1/3). After completion of the reaction, the catalyst was removed easily by an
external magnet and the residual product was collected by filtration and washed with ethanol and recrystallized to yield pure products. The
recycled magnetic nanocomposite was washed, dried and re-used several times in subsequent reactions without further treatments.
2.4. General procedure for synthesis of polyhydroquinoline derivatives 6a-s
At first, 3 mg of -Fe2O3/Cu@cellulose nanobiocomposite was added to the mixture of an aromatic aldehyde (1.0 mmol), 1,3-cyclohexandione
or dimedone (1.0 mmol), ethylacetoacetate (1.0 mmol) and ammonium acetate (2.0 mmol) in a 5-mL round bottom flask. Then, the mixture
was homogenized and stirred at room temperature for 20 min. The progress of the reaction was monitored by TLC (ethyl acetate/n-hexane
1/3). After completion of the reaction, 5 mL of ethyl acetate was added and the solid catalyst was separated by an external magnet. The crude
products were recrystallized from ethyl acetate/n-hexane to achieve the pure products in high yields. The recycled magnetic nanocomposite
was washed, dried and re-used several times in subsequent reactions without further treatments.
2.5. Spectral data of representative compounds
2.5.1. Ethyl 2,7,7-trimethyl-5-oxo-4-p-tolyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6c)
1
FT-IR (KBr) (υmax, cm-1) = 3276, 3205, 2958, 1701, 1647, 1604, 1492, 1379, 1215, 1033. H NMR (300 MHz, CDCl3): δH (ppm) = 0.96 (3H,
s, CH3), 1.08 (3H, s, CH3), 1.26 (3H, t, J = 7.2 Hz, CH3), 2.26 (3H, s, CH3), 2.22-2.34 (4H, m, 2CH2), 2.38 (3H, s, CH3), 4.16 (2H, q, J = 7.2
Hz, OCH2), 5.43 (1H, s, CH), 6.19 (1H, br s, NH); 6.84 (2H, d, J = 7.5 Hz, H-Ar), 7.03 (2H, d, J = 7.5 Hz, H-Ar). Anal. Calcd for C22H27NO3:
C, 74.76; H, 7.70; N, 3.96. Found: C, 74.71; H, 7.66; N, 4.03.
2.5.2. Ethyl 4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6d)
1
FT-IR (KBr) (υmax, cm-1) = 3274, 3205, 3076, 2960, 1704, 1647, 1604, 1488, 1380, 1278, 1215, 1070. H NMR (300 MHz, CDCl3): δH (ppm)
= 0.93 (3H, s, CH3), 1.08 (3H, s, CH3), 1.20 (3H, t, J = 7.1 Hz, CH3), 2.06-2.31 (4H, m, 2CH2), 2.38 (3H, s, CH3), 4.06 (2H, q, J = 7.1 Hz,
OCH2), 5.03 (1H, s, CH), 6.23 (1H, br s, NH), 7.16 (2H, d, J = 8.1 Hz, H-Ar), 7.26 (2H, d, J = 8.4 Hz, H-Ar). Anal. Calcd for C21H24ClNO3:
C, 67.46; H, 6.47; N, 3.75. Found: C, 67.32; H, 6.54; N, 3.82.
2.5.2. Ethyl 2,7,7-trimethyl-5-oxo-4-(thiophen-2-yl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (6m)
1
FT-IR (KBr) (υmax, cm-1) = 3274, 3207, 2960, 1701, 1647, 1604, 1492, 1379, 1215, 1072. H NMR (300 MHz, CDCl3): δH (ppm) = 1.04 (3H,
s, CH3), 1.10 (3H, s, CH3), 1.27 (3H, t, J = 7.1 Hz, CH3), 2.22-2.34 (4H, m, 2CH2), 2.38 (3H, s, CH3), 4.16 (2H, q, J = 7.1 Hz, OCH2), 5.42
(1H, s, CH), 6.19 (1H, br s, NH), 6.84 (2H, d, J = 1.8 Hz, H-Ar), 7.03 (1H, t, J = 2.1 Hz, H-Ar). Anal. Calcd for C19H23NO3S: C, 66.06; H,
6.71; N, 4.05. Found: C, 67.11; H, 6.63; N, 3.94.
5

3. Results and discussion
3.1. Catalyst identification
Initially, Cu and magnetic -Fe2O3 nanoparticles were synthesized by co-precipitation method on microcrystalline cellulose. As indicated in
Fig. 2c,d, the size and morphology of the nanocomposite were studied by conventional nanomaterials analysis instruments especially FE-SEM.
As can be seen, Spherical nanoparticles are well distributed on the cellulose surface. FE-SEM images showed the homogeneous structure of
the catalyst and the cellulose layer was also clearly observed. The nanoparticles were suitably supported by the cellulose. The average size
distribution of the nanoparticles was about 25-55 nm. FE-SEM image of the cellulose matrix after its solubilization in NaOH/Urea/H2O mixture
(without modification) is shown in Fig. 2a,b, which have uniform and flat surface before the stabilization of the nanoparticles. To study the
elemental composition of -Fe2O3/Cu@cellulose an EDX analysis was provided. An EDX analysis was provided to approve the presence of
C, O, Cu and Fe elements in the nanocomposite structure (Fig. 2e). By comparing Fig. 2e with Fig. 2f, it was confirmed that there is no
considerable difference between the values of the elements in the primary catalyst and recycled catalyst. In addition, ICP-AES analysis of the
-Fe2O3/Cu@cellulose nanocomposite indicated that the Cu content in the nanocomposite was about 10%.
The prepared nanocomposite was studied by TEM technique (Fig. 2g,h). It was used to confirm the nanocomposites morphology. TEM
proved that -Fe2O3 and Cu nanoparticles were effectively diffused in cellulose texture by electrostatic forces or chemical interactions. By
comparing Fig. 2g,h with Fig. 2i,j, it was proved that there is no considerable difference in the chemical structure of the catalyst between the
values of the elements in the primary catalyst and recycled catalyst. Finally, to determine the average size distribution of the nanoparticles, 100
particles were used randomly and the sizes of most of the nanoparticles were less than 30 nm.
a
b
c
d
e
f
6

g
h
i
j
Fig. 2
images of
of recycled
-Fe2O3/Cu@cellulose.
.
a,b) FE-SEM images of the cellulose matrix after its solubilization in NaOH/Urea/H2O mixture without adding nanoparticles c,d) FE-SEM

-Fe2O3/Cu@cellulose nanostructure with different magnifications, e) EDX analysis of primary
-Fe2O3/Cu@cellulose and f) EDX analysis

-Fe2O3/Cu@cellulose, g,h,) TEM images of primary -Fe2O3/Cu@cellulose with different magnifications, i,j) TEM images of recycled


XRD pattern analysis was also used to determine the structure of the nanocatalyst. The XRD pattern of the -Fe2O3/Cu@cellulose
nanocomposite is shown in Fig. 3. The peak in region 2= 20 degree, which is a curved peak, represents the cellulose substrate and cellulose
XRD. The sharp peaks in the region of 30 to 65 degrees are related to -Fe2O3 and Cu nanoparticles on its surface and the position of all
diffraction peaks match well with those of a lattice cubic system of -Fe2O3 peaks. This could easily be proven by comparing with the
-Fe2O3 and Cu JCPDS.
7

Fig. 3. XRD pattern of the -Fe2O3/Cu@cellulose nanobiocomposite.
FT-IR spectrum indicates the formation of -Fe2O3/Cu@cellulose. Fig. 4 shows the FT-IR spectra of -Fe2O3/Cu@cellulose in comparison
with -Fe2O3@cellulose and recycled nanocomposite after 5 times reusing in the organic reactions. A broad peak was observed at about 3350
cm-1 which can be related to stretching mode of OH groups on cellulose of the nanocomposite structure. Hydrogen bonds are the reason of
broadness of this peak. In the spectrum of-Fe2O3/Cu@cellulose, a peak appeared at 460 cm-1 that is possibly originated from Fe–O bonds in
-Fe2O3 nanoparticles and can prove the immobilization of -Fe2O3 nanoparticles on cellulose surface. Due to addition of nanoparticles on
cellulose matrix, all of the peaks were broadened. Furthermore, by addition of Cu and -Fe2O3 to the cellulose matrix, new peaks were appeared.
Furthermore, Fig. 4 shows the catalyst stability and as can be seen from the FT-IR spectrum of the nanocatalyst, it had good chemical stability
and there was no considerable happening for its carbohydrate matrix or nanocomposite structure during the chemical reactions.
8

Fig. 4. FT-IR spectra of -Fe2O3/Cu@cellulose in comparison to -Fe2O3@cellulose and recycled -Fe2O3/Cu@cellulose.
The thermal behavior of the prepared nanocomposite was investigated by TG/DTA analyses over the temperature range of 50-700 °C at
air atmosphere (Fig. 5a,b). Thermal analysis identified three separate weight loss regions on the TG curve. As displayed in this figure, -
Fe2O3/Cu@cellulose starts to slight loss of mass upon heating at about 100-200 °C, is due to the removal of volatile elements like water from
the nanocomposite. The TGA/DTA results showed that the most mass loss was occurred at about 300−350 °C, that can be associated to the
decomposition of functional groups of cellulose and so about 600 °C is due to the decomposition of carbonaceous structure of cellulose linked
to nanoparticles. Noteworthy, due of the catalyst's stability of up to 300 °C, this new nanobiocomposite can be used in organic reactions.
Based on AFM analysis, the surface and layers of the nanocatalyst was studied in details. As shown in Fig. 5c, the catalyst level is out of
uniformity and surface morphology altered from cellulose and also Fe2O3 and Cu. This evidence can be claimed as an important proof for
shaping of -Fe2O3/Cu@cellulose nanostructure as well as its nanostructure dimensions and morphology.
9

c
Fig. 5. a,b) TGA and DTA curves and c) AFM image of the -Fe2O3/Cu@cellulose nanobiocomposite.
3.2. To study of -Fe2O3/Cu@cellulose catalytic activity in the synthesis of 1,4-dihydropyridine and polyhydroquinolines
To optimize the reaction conditions for the synthesis of 1,4-dihydropyridine derivatives, the reaction of the 4-chlorobenzaldehyde (1 mmol),
ethylacetoacetate (2 mmol) and ammonium acetate (2 mmol) was considered as a model reaction. In the case of polyhydroquinolines, dimedone
was used instead of ethylacetoacetate. Both of these reactions were carried out in the presence of various solvents like ethanol, water and
acetonitrile and also under solvent-free conditions. The best yield was obtained under solvent-free conditions (Table 1).
To find the optimized catalyst ratio, different amounts of the nanocatalyst were studied (Table 1). At first, this reaction was performed
under catalyst-free conditions. But, the yield of the product was low after 1 h. Therefore, the presence of the catalyst was necessary for the
completion of the reaction. The best quantity of the catalyst for the synthesis of 1,4-dihydropyridine and polyhydroquinoline was 3 mg. By
increasing the amount of the catalyst the reaction yield did not increase.
Table 1. Screening of the of -Fe2O3/Cu@cellulose amounts and solvents effects on the model reactions.
Dihydropyridinea
Polyhydroquinolineb
Entry
Solvent
Catalyst (g)
Time (min)
Yield (%)
25
Time (min)
Yield (%)
40
1
2
3
4
5
6
7
8
9
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Ethanol
-
240
20
20
20
20
20
40
80
80
240
15
15
15
15
15
40
80
80
0.002
0.003
0.004
0.008
0.02
80
80
92
95
92
95
85
91
85
87
0.003
0.003
0.003
87
90
Water
trace
60
trace
60
Acetonitrile
a Reaction conditions: 1 mmol of 4-chlorobenzaldehyde, 2 mmol of ethyl acetoacetate and 2 mmol of ammonium acetate.
b Reaction conditions: 1 mmol of 4-chlorobenzaldehyde, 1 mmol of ethyl acetoacetate, 1 mmol of dimedone and 2 mmol ammonium acetate.
The scope and generality of the synthesis of 1,4-dihydropyridine and polyhydroquinoline derivatives were studied by using various
aromatic aldehydes (Tables 2 and 3). Diverse 1,4-dihydropyridine and polyhydroquinolines were synthesized with the aforementioned molar
10

ratios starting from various aldehydes and 1,3-diketones under optimized solvent-free conditions and easy work-up procedures. Various
aldehydes bearing both electron-withdrawing and electron-donating groups were checked out in these reactions. Due to the formation of the
imine intermediate in the reaction of aldehydes with electron-withdrawing groups which is an inappropriate factor, these kinds of aldehydes
were not reacted so well. But, in the presence of electron-donating groups, the reaction was progressed in short times and high yields. As shown
in Table 3, entries 9 and 10, steric hindrance effects were not observed. The results clearly showed that the reaction of various aromatic
aldehydes, ethyl acetoacetate, ammonium acetate and dimedone or 1,3-cyclohexandione under solvent-free conditions in the presence of the
nanocomposite provided the corresponding products in high yields and appropriate reaction times. Some of the products were synthesized for
the first time and were characterized by melting points, IR and NMR spectral data.
Table 2. Synthesis of 1,4-dihydropyridine derivatives 5a-i by using various aldehydes, ammonium acetate and ethyl acetoacetate catalysed by -
Fe2O3/Cu@cellulose. a
Entry
1
Aldehyde
C6H5
Product
5a
Time (min)
25
Yield (%)
87
Mp (°C)
155
Mp (°C, ref.)
154-156
(Maleki, et al., 2018)
156-158
(Moradi, et al.,2018)
141-143
2
3
4
4-OMeC6H4
4-MeC6H4
4-ClC6H4
5b
5c
5d
15
15
20
92
91
92
153-154
136-137
145-147
(Moradi, et al.,2018)
144-146
(Maleki, et al., 2018)
5
4-BrC6H4
5e
20
82
162-163
160-162
(Maleki, et al., 2018)
6
7
8
9
4-NO2C6H4
3-NO2C6H4
5f
5g
5h
5i
20
35
20
15
85
80
93
90
134
127-129
(Maleki, et al., 2018)
163-164
(Maleki, et al., 2018)
171-172
160-163
170-171
161-162
Thiophene-2-carbaldehyde
Furfural
(Debache et al., 2009)
162-164
(Debache et al., 2009)
a Reaction conditions: Aldehyde (1 mmol), ethyl acetoacetate (2 mmol), ammonium acetate (2 mmol) and -Fe2O3/Cu@cellulose (3 mg), room
temperature, solvent-free conditions.
Table 3. Synthesis of polyhydroquinoline derivatives 6a-s by using various aldehydes, dimedone, ethyl acetoacetate and ammonium acetate in the presence of
-Fe2O3/Cu@cellulose. a
Entry
1
Aldehyde
C6H5
1,3-Diketone
Dimedone
Product
6a
Time (min)
20
Yield (%)
87
Mp (°C )
201
Mp (°C, ref.)
203-205
(Tajbakhsh et al., 2013)
2
4-MeOC6H4
Dimedone
6b
10
90
256
256-258
(Moradi, et al.,2018)
3
4
5
4-MeC6H4
4-ClC6H4
2-ClC6H4
Dimedone
Dimedone
Dimedone
6c
6d
6e
10
15
15
91
95
87
255
240
254-256
(Moradi, et al.,2018)
241-243
(Maleki et al., 2012)
201-202
202-205
(Mobinikhaledi et al., 2009)
6
4-OHC6H4
Dimedone
6f
15
82
230-240
232-234
(Heydari et al., 2009)
7
8
2-OHC6H4
4-NO2C6H4
Dimedone
Dimedone
6g
6h
15
35
90
80
214
216-218
(Tajbakhsh et al., 2013)
238-240
238-240
(Moradi, et al.,2018)
9
3-OMe,4-OHC6H4
Dimedone
6i
20
95
222-225
225-227
(Kumar, & Maurya, 2007)
10
11
2,4-OMe,5-OHC6H4
4-BrC6H4
Dimedone
Dimedone
6j
20
20
95
87
154-157
253-254
Not reported
6k
259-260
(Davoodnia, Khashi, &
Tavakoli-Hoseini, 2013)
143-145
12
4-CNC6H4
Dimedone
6l
30
80
139-142
(Tajbakhsh et al., 2013)
11

13
14
15
Thiophene-2-carbaldehyde
Furfural
Dimedone
Dimedone
6m
6n
6o
15
15
9
93
91
95
225
243-244
250
226-228
(Moradi, et al.,2018)
245-247
(Tajbakhsh et al., 2013)
4-OMeC6H4
1,3-Cyclohexandione
248-253
(Ghattali, Saidi, &
Khabazzadeh, 2014)
241-243
16
17
18
19
4-MeC6H4
4-ClC6H4
1,3-Cyclohexandione
1,3-Cyclohexandione
1,3-Cyclohexandione
1,3-Cyclohexandione
6p
6q
6r
6s
9
95
98
90
95
244-245
239
(Nasr-Esfahani et al., 2014)
15
15
10
234-236
(Nasr-Esfahani et al., 2014)
4-OHC6H4
224-227
232
222-224
(Nasr-Esfahani et al., 2014)
Thiophene-2-carbaldehyde
232-234
(Nasr-Esfahani et al., 2014)
a Reaction conditions: Aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (2 mmol) and -Fe2O3/Cu@cellulose (3 mg),
room temperature, solvent-free conditions.
The reusability of -Fe2O3/Cu@cellulose nanocatalyst was examined in the model reactions for the synthesis of 1,4-dihydropyridines and
polyhydroquinolines (Fig. 6). In both of these reactions, the catalyst was easily recycled at least five times without significant loss of activity.
In this regard, after completion of the reaction, the catalyst was separated by an external magnet, washed with hot ethanol and dried at room
temperature to be ready for the subsequent runs. To study possible leaching of the nanocomposite components, an ICP-OES analysis was
provided after the last recycling. It was found that the percentages of the elements were not changed significantly and the rest of Cu was still
about 10%.
92
95
90 93
88 90
85
89
83 88
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
5
Run
1,4-dihydro pyridine
Polyhydroquinoline
Fig. 6. Examination of -Fe2O3/Cu@cellulose reusability in the synthesis of 1,4-dihydropyridine (5d) and polyhydroquinoline (6d).
To show the efficiency of -Fe2O3/Cu@cellulose nanocatalyst, it was compared with literature resulted in reports of using various catalysts
for the synthesis of 1,4-dihydropyridines and polyhydroquinolines. A few catalysts are reported for these reactions such as MgAl2-HT, cellulose
sulfuric acid, NaHSO4-SiO2, [TBA]2[W6O19], PPh3 and Fe3O4/SiO2/Pph3/[CrO3Br]-. As shown in Table 4, most of them suffer from harsh
reaction conditions such as reflux, volatile, hazardous and toxic solvents, long reaction times, low yields, expensive catalysts and tedious work-
up procedures. While, -Fe2O3/Cu@cellulose bionanocomposite is safe, green, inexpensive and easily separated from reaction pot. In order to
simply separate from the reaction mixture. To compare the role of nanocomposites, the catalytic activity of cellulose, Cu@cellulose and -
Fe2O3@cellulose were also evaluated. As the table illustrates, basic cellulose did not have enough catalytic activity; but, when the nanoparticles
were loaded, its activity was considerably increased. In addition, Cu nanoparticle had a more important role than-Fe2O3. When both of these
12

components were coated on biopolymer, their synergistic effects were appeared. Furthermore, in the absence of cellulose, despite the increase
in the amounts of the nanoparticles, the catalytic activity was not increased significantly.
Table 4. Comparison of the catalytic efficiency of -Fe2O3/Cu@cellulose with other catalysts for the synthesis of 1,4-dihydropyridine and polyhydroquinoline
derivatives.
Entry
Catalyst
Mg Al2-HT
Reaction conditions
Acetonitrile/ r.t.
Solvent-free/100 °C
Acetonitrile/r.t.
Solvent-free/110 °C
EtOH/reflux
Time (min)
Yield (%)
Literature
(Antonyraj, & Kannan, 2008)
(Murthy et al., 2012)
1
2
3
4
5
6
7
390
300
360
20
53
78
80
95
81
89
95
Cellulose sulfuric acid
NaHSO4-SiO2
(Chari, & Syamasundar, 2005)
(Debache et al., 2009)
[TBA]2[W6O19]
PPh3
120
60
(Davoodnia, Khashi, & Tavakoli-Hoseini, 2013)
(Maleki et al., 2014)
Fe3O4/SiO2/PPh3/[CrO3Br]-
-Fe2O3/Cu@cellulose
EtOH /r.t.
EtOH/r.t.
15
Present work
8
EtOH/r.t.
60
30
Present work
-Fe2O3 nanoparticles
A plausible mechanism for the formation of 1,4-dihydropyridine and polyhydroquinoline derivatives is shown in Fig. 7. -Fe2O3/Cu@cellulose
can activate the reactants and also some intermediates in this reaction. On the basis of the literature and substrates chemistry, the first step is
the formation of an intermediate I from the condensation reaction between an aromatic aldehyde 1 and dimedone 3, or 1,3-ketoesters 4 in the
presence of -Fe2O3/Cu@cellulose. Then, the addition of the second mole of 3 or 4 to I produces intermediate II. After that, the reaction
between amine part of NH4OAc and carbonyl group of II yields intermediate III. Finally, it was followed by an imine–enamine tautomerization
to afford the final products 5a-i or 6a-s.
13

Fig. 6. Proposed mechanism for the synthesis of 1,4-dihydropyridine and polyhydroquinoline derivatives using -Fe2O3/Cu@cellulose.
4. Conclusions
In summary, we have prepared and characterized an efficient cellulose-based magnetic bionanocomposite. Biopolymer-based bimetallic
bionanocomposite was prepared via in situ synthesis of maghemite (-Fe2O3) and immobilization of Cu on cellulose. Furthermore, the catalytic
performance of the bionanocomposite was investigated in two important multicomponent condensation reactions for the synthesis of 1,4-
dihydropyridine and polyhydroquinoline derivatives starting from simple and readily accessible precursors under solvent-free conditions at
room temperature. A large number of unique properties of this novel composite nanocatalyst were observed including short reaction times,
simple work-up procedure, reusability of the nanocatalyst, high atom economy, high yields and environmentally-benign reaction conditions.
Several analytical methods were used for the characterization of the nanocatalyst. Cu-embedded nanocomposite catalyst was successfully
magnetized by -Fe2O3 nanoparticles and simultaneously immobilized on carbohydrate cellulose matrix to yield -Fe2O3/Cu@cellulose. FE-
SEM and TEM images of the bionanocomposite were indicated that a narrow size distribution of Cu and -Fe2O3 nanoparticles which are
distributed on the biomatrix as well as uniform morphology. EDX and ICP analysis clearly showed the presence of Fe, Cu, C and O elements
in the fresh and recycled nanocomposite. Therefore, leaching was not happened during the organic reactions and reusing of the nanocatalyst
after several runs. This finding can be regarded as an important factor in large-scale production. AFM and TGA analyzes were used to further
investigate the catalysts' characteristics. AFM image confirmed that the surface and layers of the nanocatalyst was out of uniformity and surface
morphology altered from cellulose and also Fe2O3 and Cu in -Fe2O3/Cu@cellulose nanostructure. The appropriate thermal stability behavior
of the prepared nanocomposite was approved by TG/DTA analyses over the temperature range of 50-700 °C at air atmosphere.
Acknowledgements
14

The authors gratefully acknowledge the partial support from the Research Council of the Iran University of Science and Technology.
Notes and references
Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-
13114, Iran
*Corresponding author. Tel.: +98 21 77240640-50; Fax: +98 21 73021584. E-mail: maleki@iust.ac.ir (A. Maleki).
Antonyraj, C. A., & Kannan, S. (2008). Hantzsch pyridine synthesis using hydrotalcites or hydrotalcite-like materials as solid base
catalysts. Applied Catalysis A: General, 338, 121-129.
Baran, N. Y., Baran, T., & Menteş, A. (2018). Production of novel palladium nanocatalyst stabilized with sustainable chitosan/cellulose
composite and its catalytic performance in Suzuki-Miyaura coupling reactions. Carbohydrate Polymers, 181, 596-604.
Baran, T. (2018). Pd (0) nanocatalyst stabilized on a novel agar/pectin composite and its catalytic activity in the synthesis of biphenyl
compounds by Suzuki-Miyaura cross coupling reaction and reduction of o-nitroaniline. Carbohydrate Polymers, 195, 45-52.
Baran, T. (2018). Ultrasound-accelerated synthesis of biphenyl compounds using novel Pd(0) nanoparticles immobilized on bio-
composite. Ultrasonics Sonochemistry, 45, 231-237.
Baran, T., Yılmaz Baran, N., & Menteş, A. (2018). Sustainable chitosan/starch composite material for stabilization of palladium nanoparticles:
Synthesis, characterization and investigation of catalytic behaviour of Pd@chitosan/starch nanocomposite in Suzuki–Miyaura
reaction. Applied Organometallic Chemistry, 32(2), e4075.
Boer, R., & Gekeler, V., (1995). Drugs Future, 20, 499.
Bossert, F., Meyer, H., & Wehinger, E. (1981). 4‐Aryldihydropyridines, a new class of highly active calcium antagonists. Angewandte Chemie
International Edition in English, 20, 762-769.
Briukhanov, V. M., (1994). The effect of Ca antagonist on the development of inflammatory edema in rats. Clinical and Experimental
Pharmacology, 57, 47–49.
Chari, M. A., & Syamasundar, K. (2005). Silicagel/NaHSO4 catalyzed one-pot synthesis of Hantzsch 1,4-dihydropyridines at ambient
temperature.Catalysis Communications, 6, 624-626.
Cosconati, S., Marinelli, L., Lavecchia, A., & Novellino, E. (2007). Characterizing the 1, 4-dihydropyridines binding interactions in the L-type
Ca2+ channel: model construction and docking calculations. Journal of Medicinal Chemistry, 50, 1504-1513.
David J. T., (2007). Calcium channel antagonists: Clinical uses—Past, present and future. Biochemical Pharmacology, 74, 1-9.
Davoodnia, A., Khashi, M., & Tavakoli-Hoseini, N. (2013). Tetrabutylammonium hexatungstate [TBA]2[W6O19]: Novel and reusable
heterogeneous catalyst for rapid solvent-free synthesis of polyhydroquinoline via unsymmetrical Hantzsch reaction. Chinese Journal
of Catalysis, 34, 1173-1178.
Debache, A., Ghalem, W., Boulcina, R., Belfaitah, A., Rhouati, S., & Carboni, B. (2009). An efficient one-step synthesis of 1,4-
dihydropyridines via a triphenylphosphine-catalyzed three-component Hantzsch reaction under mild conditions. Tetrahedron
Letters, 50, 5248-5250.
Donelson, J. L., Gibbs, R. A., & De, S. K. (2006). An efficient one-pot synthesis of polyhydroquinoline derivatives through the Hantzsch four
component condensation. Journal of Molecular Catalysis A: Chemical, 256, 309-311.
Gawande, Manoj B., Paula S. Branco, & Rajender S. Varma. (2013). Nano-magnetite (Fe3O4) as a support for recyclable catalysts in the
development of sustainable methodologies. Chemical Society Reviews, 42, 3371-3393.
Ghattali, S. N., Saidi, K., & Khabazzadeh, H. (2014). (NH4)2.5H0.5PW12O40-catalyzed rapid and efficient one-pot synthesis of
dihydropyridines via the Hantzsch reaction under solvent-free conditions. Research on Chemical Intermediates, 40, 281-291.
Gilpin, R. K., & Pachla, L. A. (1999). Pharmaceuticals and related drugs. Analytical Chemistry, 71, 217-234.
Gullapalli, S., & Ramarao, P. (2002). L-Type Ca2+ channel modulation by dihydropyridines potentiates κ-opioid receptor agonist induced
acute analgesia and inhibits development of tolerance in rats. Neuropharmacology, 42, 467-475.
Gunawan, S., Ayaz, M., De Moliner, F., Frett, B., Kaiser, C., Patrick, N., Xu, Z. & Hulme, C., (2012). Synthesis of tetrazolo-fused
benzodiazepines and benzodiazepinones by
generation. Tetrahedron, 68, 5606-5611.
a two-step protocol using an Ugi-azide reaction for initial diversity
Habibi, Y., Lucia, L. A., & Rojas, O. J. (2010). Cellulose nanocrystals: chemistry, self-assembly, and applications. Chemical reviews, 110(6),
3479-3500.
Heydari, A., Khaksar, S., Tajbakhsh, M., & Bijanzadeh, H. R. (2009). One-step, synthesis of Hantzsch esters and polyhydroquinoline
derivatives in fluoro alcohols. Journal of Fluorine Chemistry, 130, 609-614.
Hulme, C., Peng, J., Tang, S. Y., Burns, C. J., Morize, I., & Labaudiniere, R. (1998). Improved procedure for the solution phase preparation
of 1,4-benzodiazepine-2,5-dione libraries via Armstrong's convertible isonitrile and the Ugi reaction. The Journal of Organic
Chemistry, 63, 8021-8023.
Klemm, D., Heublein, B., Fink, H. P., & Bohn, A. (2005). Cellulose: fascinating biopolymer and sustainable raw material. Angewandte Chemie
International Edition, 44(22), 3358-3393.
Kumar, A., & Maurya, R. A. (2007). Bakers’ yeast catalyzed synthesis of polyhydroquinoline derivatives via an unsymmetrical Hantzsch
reaction.Tetrahedron letters, 48, 3887-3890.
Li, M., Zuo, Z., Wen, L., & Wang, S. (2008). Microwave-assisted combinatorial synthesis of hexa-substituted 1,4-dihydropyridines scaffolds
using one-pot two-step multicomponent reaction followed by a S-alkylation. Journal of combinatorial chemistry, 10, 436-441.
15

Lian, C., Liu, H., Xiao, C., Yang, W., Zhang, K., Liu, Y., & Wang, Y., (2012). Solvent-free selective hydrogenation of chloronitrobenzene to
chloroaniline over a robust Pt/Fe3O4 catalyst. Chemical Communications, 48, 3124-3126.
Maheswara, M., Siddaiah, V., Damu, G. L. V., & Rao, C. V. (2006). An efficient one-pot synthesis of polyhydroquinoline derivatives via
Hantzsch condensation using a heterogeneous catalyst under solvent-free conditions.Arkivoc, 2, 201-206.
Maleki, A., Firouzi-Haji, R., & Hajizadeh, Z. (2018). Magnetic guanidinylated chitosan nanobiocomposite: A green catalyst for the synthesisof
1, 4-dihydropyridines. International Journal of Biological Macromolecules, 116, 320-326.
Maleki, A., Jafari, A. A., & Yousefi, S. (2017). Green cellulose-based nanocomposite catalyst: design and facile performance in aqueous
synthesis of pyranopyrimidines and pyrazolopyranopyrimidines. Carbohydrate Polymers, 175, 409-416.
Maleki, A., Jafari, A. A., Yousefi, S., & Eskandarpour, V. (2015). An efficient protocol for the one-pot multicomponent synthesis of
polysubstituted pyridines by using a biopolymer-based magnetic nanocomposite. Comptes Rendus Chimie, 18, 1307-1312.
Maleki, A., Movahed, H., & Paydar, R. (2016). Design and development of a novel cellulose/γ-Fe2O3/Ag nanocomposite: a potential green
catalyst and antibacterial agent. RSC Advances, 6, 13657-13665.
Maleki, A., Movahed, H., & Ravaghi, P. (2017). Synthesis of magnetic cellulose/Ag as a novel environmentally friendly nanobiocomposite
catalyst to achieve chromene-linked 2-amino-4-aryl-nicotinonitrile derivatives. Carbohydrate Polymers, 156, 259-267.
Maleki, A. & Paydar, R. (2016). Bionanostructure-catalyzed one-pot three-component synthesis of 3, 4-dihydropyrimidin-2 (1H)-one
derivatives under solvent-free conditions. Reactive and Functional Polymers, 109, 120-124.
Maleki, A., Rahimi, J., Demchuk, O. M., Wilczewska, A. Z., & Jasiński, R. (2018). Green in water sonochemical synthesis of
tetrazolopyrimidine derivatives by a novel core-shell magnetic nanostructure catalyst. Ultrasonics Sonochemistry, 43, 262-271.
Maleki, A., Rahimi, R., Maleki, S., & Hamidi, N. (2014). Synthesis and characterization of magnetic bromochromate hybrid nanomaterials
with triphenylphosphine surface-modified iron oxide nanoparticles and their catalytic application in multicomponent reactions. RSC
Advances, 4, 29765-29771.
Maleki, A., & Sarvary, A. (2015). Synthesis of tetrazoles via isocyanide-based reactions. RSC Advances, 5, 60938-60955.
Maleki, A., Zand, P., Mohseni, Z., & Firouzi-Haji, R. (2018). Green composite nanostructure (Fe3O4@PEG-SO3H): Preparation,
characterization and catalytic performance in the efficient synthesis of β-amino carbonyl compounds at room temperature. Nano-
Structures & Nano-Objects, 16, 31-37.
Mekheimer, R. A., Hameed, A. A., & Sadek, K. U. (2008). Solar thermochemical reactions: four-component synthesis of polyhydroquinoline
derivatives induced by solar thermal energy. Green Chemistry, 10, 592-593.
Mobinikhaledi, A., Foroughifar, N., Fard, M. A. B., Moghanian, H., Ebrahimi, S., & Kalhor, M. (2009). Efficient one-pot synthesis of
polyhydroquinoline derivatives using silica sulfuric acid as a heterogeneous and reusable catalyst under conventional heating and
energy-saving microwave irradiation. Synthetic Communications, 39, 1166-1174.
Moradi, L., & Zare, M. (2018). Ultrasound-promoted green synthesis of 1,4-dihydropyridines using fuctionalized MWCNTs as a highly
efficient heterogeneous catalyst. Green Chemistry Letters and Reviews, 11(3), 197-208.
Murthy, Y. L. N., Rajack, A., Ramji, M. T., Praveen, C., & Lakshmi, K. A. (2012). Design, solvent free synthesis, and antimicrobial evaluation
of 1, 4 dihydropyridines. Bioorganic & Medicinal Chemistry Letters, 22, 6016-6023.
Nasr-Esfahani, M., Hoseini, S. J., Montazerozohori, M., Mehrabi, R., & Nasrabadi, H. (2014). Magnetic Fe3O4 nanoparticles: efficient and
recoverable nanocatalyst for the synthesis of polyhydroquinolines and Hantzsch 1, 4-dihydropyridines under solvent-free
conditions. Journal of Molecular Catalysis A: Chemical, 382, 99-105.
Orru, R. V., & de Greef, M. (2003). Recent advances in solution-phase multicomponent methodology for the synthesis of heterocyclic
compounds.Synthesis, 2003, 1471-1499.
Pagoti, S., Surana, S., Chauhan, A., Parasar, B., & Dash, J. (2013). Reduction of organic azides to amines using reusable Fe3O4 nanoparticles
in aqueous medium. Catalysis Science & Technology, 3, 584-588.
Polshettiwar, V., Baruwati, B., &Varma, R.S. (2009). Nanoparticle-supported and magnetically recoverable nickel catalyst: a robust and
economic hydrogenation and transfer hydrogenation protocol. Green Chemistry, 11, 127-131.
Reddy, C. S., & Raghu, M. (2008). Cerium (IV) ammonium nitrate catalysed facile and efficient synthesis of polyhydroquinoline derivatives
through Hantzsch multicomponent condensation. Chinese Chemical Letters, 19, 775-779.
Rostamnia, S., Lamei, K., Mohammadquli, M., Sheykhan, M., & Heydari, A. (2012). Nanomagnetically modified sulfuric acid (γ-Fe2O3@
SiO2-OSO3H): an efficient, fast, and reusable green catalyst for the Ugi-like Groebke-Blackburn-Bienaymé three-component reaction
under solvent-free conditions.Tetrahedron Letters, 53, 5257-5260.
Shafiee, M., Khosropour, A. R., Mohammadpoor-Baltork, I., Moghadam, M., Tangestaninejad, S., & Mirkhani, V. (2012). A new green
catalyst: 1,3,5-triazine-functionalized bisimidazolium dichloride tethered SPION catalyzed Betti synthesis. Catalysis Science &
Technology, 2, 2440-2444.
Spiridonov, V. V., Panova, I. G., Makarova, L. A., Afanasov, M. I., Zezin, S. B., Sybachin, A. V., & Yaroslavov, A. A. (2017). The one-step
synthesis of polymer-based magnetic γ-Fe2O3/carboxymethyl cellulose nanocomposites. Carbohydrate polymers, 177, 269-274.
Tajbakhsh, M., Alinezhad, H., Norouzi, M., Baghery, S., & Akbari, M. (2013). Protic pyridinium ionic liquid as a green and highly efficient
catalyst for the synthesis of polyhydroquinoline derivatives via Hantzsch condensation in water. Journal of Molecular Liquids, 177,
44-48.
Tu, S. J., Zhou, J. F., Deng, X., Cai, P. J., Wang, H., & Feng, J. C. (2001). One step synthesis of 4-arylpolyhydroquinoline derivatives using
microwave irradiation. Chinese Journal of Organic Chemistry, 21(4), 313-316.
Wang, L. M., Sheng, J., Zhang, L., Han, J. W., Fan, Z. Y., Tian, H., & Qian, C. T. (2005). Facile Yb(OTf)3 promoted one-pot synthesis of
polyhydroquinoline derivatives through Hantzsch reaction. Tetrahedron, 61, 1539-1543.
Xu, Q., Chen, C., Rosswurm, K., Yao, T., & Janaswamy, S. (2016). A facile route to prepare cellulose-based films. Carbohydrate
Polymers, 149, 274–281.
16

Yan, J. M., Zhang, X. B., Akita, T., Haruta, M., & Xu, Q. (2010). One-step seeding growth of magnetically recyclable Au@Co core− shell
nanoparticles: highly efficient catalyst for hydrolytic dehydrogenation of ammonia borane. Journal of the American Chemical
Society, 132, 5326-5327.
Yu, X., Tong, S., Ge, M., Zuo, J., Cao, C., & Song, W. (2013). One-step synthesis of magnetic composites of cellulose@iron oxide
nanoparticles for arsenic removal. Journal of Materials Chemistry, 1(3), 959-965.
Zhu, J., & Bienaymé, H. (Eds.). (2005). Multicomponent reactions. John Wiley & Sons, Ltd, Weinheim.
17