Fe3O4 nano-particles supported on cellulose as an efficient catalyst for the synthesis of pyrimido[4,5-b]quinolines in water

Article abstract of DOI:10.1007/s00706-014-1368-5

Fe₃O₄ nano-particles supported on cellulose were provided as a catalyst via in situ preparation of Fe₃O₄ nano-particles and their deposition on cellulose. This catalyst, after characterization with TEM and FAAS

Full text of DOI:10.1007/s00706-014-1368-5

Monatsh Chem
DOI 10.1007/s00706-014-1368-5
ORIGINAL PAPER
Fe3O4 nano-particles supported on cellulose as an efficient catalyst
for the synthesis of pyrimido[4,5-b]quinolines in water
•
Laden Edjlali Rahim Hosseinzdeh Khanamiri
•
Jafar Abolhasani
Received: 13 May 2014 / Accepted: 24 November 2014
Ó Springer-Verlag Wien 2014
Abstract Fe3O4 nano-particles supported on cellulose
were provided as a catalyst via in situ preparation of Fe3O4
nano-particles and their deposition on cellulose. This cat-
alyst, after characterization with TEM and FAAS analyses,
was used as an efficient heterogeneous catalyst for the
synthesis of pyrimido[4,5-b]quinolines. Three-component
reaction of various aromatic aldehydes, 6-amino-1,3-dim-
ethyluracil, and dimedone or 1,3-cyclohexadione in H2O as
a green solvent under reflux conditions after 2 h gave py-
rimido[4,5-b]quinolines in high yields. Fe3O4 supported on
cellulose was recycled in the reaction for 5 cycles without
significant decrease in activity.
modifying capacity. These abilities of the cellulose make it
an interesting support in catalytic reactions [3].
Quinolines are important heterocyclic compounds due to
their various biological and pharmaceutical activities [4].
Some important drugs such as quinine, chloroquine, luot-
onine-A, and camptothecin have quinoline moiety [5].
Pyrimidine-containing organic compounds are of growing
interest due to their biological potencies such as AbI kinase
inhibitor, tyrosine phosphatase inhibitor, antiviral and cal-
cium channel antagonist activities [6–8]. Some
functionalized pyrimidines have also been identified as a
new class of fibroblast growth factor receptor (FGFR3)
tyrosine kinase inhibitors [9]. Recently, significant
attempts were performed to the synthesis of pyrimido[4,5-
b]quinolines as a combination of pyrimidine and quinoline
chemistry via multi-component reactions using various
catalysts [10–18].
Keywords Fe3O4 nano-particles Á Cellulose Á
Pyrimidine Á Quinoline Á Heterogeneous catalyst
Introduction
Herein, Fe3O4 NPs supported on cellulose (Fe3O4NPs-
cell) was prepared as a heterogeneous recoverable catalyst
and applied for the synthesis of pyrimido[4,5-b]quinolines
4a–4q in H2O under reflux conditions (Scheme 1).
Today, most emphasis of chemical synthesis is on the
development of green synthetic routes with heterogeneous
catalysts and H2O media [1]. Supported magnetic nano-
particles (NPs) are interesting heterogeneous catalysts with
high surface area due to distribution of metal on the support
[2]. They generally gave higher yield in low catalyst
loading compared to conventional heterogeneous catalysts.
Cellulose is the most important biopolymer which was
used as a support. Cellulose is characterized by its hydro-
philicity, chirality, biodegradability, and broad chemical
Results and discussion
Fe3O4 NPs supported on cellulose were obtained with the
alkalinization of a mixture containing cellulose, FeSO4 and
Fe2(SO4)3 with ammonium hydroxide at 60 °C. Before
addition of ammonium hydroxide, cellulose was stirred with
FeSO4 and Fe2(SO4)3 for 1 day. Providing of these condi-
tions allowed to the primary coordination of Fe ions to
cellulose which led to the size controlling and uniform dis-
tribution of Fe3O4 NPs on the support. The results showed
that the transformation of Fe(II) and Fe(III) into Fe3O4 after
coordination to cellulose gave the homogenous smaller
L. Edjlali (&) Á R. H. Khanamiri Á J. Abolhasani
Department of Chemistry, Tabriz Branch,
Islamic Azad University, Tabriz, Iran
e-mail: sa.keshipour@yahoo.com; L_edjlali@iaut.ac.ir
123

L. Edjlali et al.
Scheme 1
Table 1 Effects of catalyst amount, solvent, and temperature on the
reaction yield
Entry
Catalyst amount/g
Solvent
Temp./°C
Yield/%a
1
0.02
0.03
0.04
0.05
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
H2O
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25
47
73
89
89
89
54
89
53
71
39
77
82
2
H2O
3
H2O
4
H2O
5
EtOH
CH2Cl2
MeOH
CH3CN
PhCH3
H2O
Fe3O4 NPs distributed on the surface and it would be able for
us to make a good conversion with low loading of Fe3O4.
Vacuum-dried Fe3O4NPs-cell was employed for the
transmission electron microscopy (TEM) and flame atomic
absorption spectroscopy (FAAS) analysis. The TEM ima-
ges of the Fe3O4NPs-cell revealed that a large number of
Fe3O4 NPs with the particles size between 11 and 24 nm
were formed and uniformly distributed onto the surface of
cellulose after deposition (Fig. 1). Fe3O4 loading in the
Fe3O4NPs-cell was determined to be 4.72 wt%, based on
FAAS analysis.
6
7
8
9
10
11
12
H2O
80
H2O
90
Reaction conditions: benzaldehyde (1a, 1.00 mmol), dimedone (2,
1.00 mmol), 6-amino-1,3-dimethyluracil (3, 1 mmol), 10 cm3 sol-
vent, 2 h
a
Isolated yield
The catalytic activity of Fe3O4NPs-cell was evaluated
for the synthesis of pyrimido[4,5-b]quinolines. For opti-
mization of the reaction conditions, the reaction of
benzaldehyde (1a), dimedone (2), and 6-amino-1,3-dim-
ethyluracil (3) as a model reaction was investigated. As
shown in the Table 1, it was found that 0.04 g of
Fe3O4NPs-cell (0.9 mol% of Fe3O4) in H2O under reflux
conditions is the best reaction condition (entry 3). It is
important to note that whilst organic solvents such as
MeOH and EtOH gave similar yields (entries 5–7), H2O
was selected as the solvent due to its accordance with the
green chemistry principle.
obtained in high yields (Table 2). The analyses of products
4a–4q have good accordance with the reports [13–18].
Recyclability of the catalyst was examined too. For this
reason, magnetically recovered Fe3O4NPs-cell from the
reaction between benzaldehyde (1a), dimedone (2), and
6-amino-1,3-dimethyluracil (3) was washed with acetone
(2 9 5 cm3), dried in the oven (60 °C, 2 h), and then used
again. This procedure was carried out for five times
(Table 3). It is clear that by successive use of the catalyst,
no decrease in the reactivity can be seen for Fe3O4NPs-cell.
In conclusion, bio-supported Fe3O4 nano-particles as a
catalyst were prepared by uniform distribution of Fe3O4
NPs (average particles size 11–24 nm) onto cellulose. This
To evaluate the use of this interesting approach, a variety
of aldehydes and cyclic 1,3-diketones 2 were examined
which good library of pyrimido[4,5-b]quinolines 4 were
Fig. 1 TEM images of Fe3O4NPs-cell sample
123

Fe3O4 nano-particles
Table 2 Synthesis of pyrimido[4,5-b]quinolines 4a–4q
Entry
Aldehyde 1
R
Product
Yield/%a
Melting point/°C
Found
Reported
1
C6H5
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
4a
4b
4c
4d
4e
4f
89
86
87
96
92
91
88
87
91
87
86
95
89
90
92
267–270
[300
268–270 [18]
[300 [15]
2
4-OHC6H4
3-NO2C6H4
4-NO2C6H5
3-BrC6H4
4-ClC6H4
2-ClC6H4
4-OCH3C6H4
4-BrC6H4
2-Thienyl
4-BrC6H4
4-NO2C6H4
4-FC6H4
3
220–222
221–224
280–283
289–292
[300
220–223 [16]
222–224 [18]
280–282 [16]
289–292 [14]
[300 [14]
4
5
6
7
4g
4h
4i
8
[300
[300 [14]
9
281–283
293–296
281–283
301–303
310–313
310–313
274–276
280–282 [14]
295–297 [15]
281–283 [15]
301–303 [13]
311–313 [13]
310–313 [17]
274–276 [13]
10
11
12
13
14
15
4j
H
4k
4m
4n
4o
4q
H
H
4-ClC6H4
4-CH3C6H4
H
H
Reaction conditions: aldehyde 1 (1.00 mmol), 2,4-diketone 2 (1.00 mmol), 6-amino-1,3-dimethyluracil (3, 1 mmol), 0.04 g Fe3O4NPs-cell,
10 cm3 H2O, reflux, 2 h
a
Isolated yield
1
measured on an Electrothermal 9100 apparatus. H NMR
spectra were recorded on a Bruker WP 200 SY spectrom-
eter 250.13 MHz in DMSO-d6 solution with TMS as
internal standard. The 13C NMR spectra were recorded at
62.47 MHz; chemical shifts (d scale) are reported in parts
per million (ppm). Transmission electron microscopy and
flame atomic absorption spectroscopy were performed by
LEO 912AB electron microscope and Shimadzu model
AA-680 atomic absorption spectrometer, respectively.
Table 3 Recycle of the catalyst
Cycle
Fe3O4-cell/g
Yield/%a
1
2
3
4
5
0.040
0.039
0.038
0.038
0.038
95
95
94
93
93
Reaction conditions: benzaldehyde (1a, 1.00 mmol), dimedone (2,
1.00 mmol), 6-amino-1,3-dimethyluracil (3, 1 mmol), 5 cm3 H2O,
reflux, 2 h
Preparation of Fe3O4NPs-cell
a
Isolated yield
Cellulose (5.0 g) was added to a solution containing 0.1 g
FeSO4Á7H2O, 0.2 g Fe2(SO4)3 and 30 cm3 H2O and stirred
for 1 day. After that, pH was adjusted to 10 with addition of
ammonium hydroxide (25 %) and the reaction mixture was
stirred for 1 h at 60 °C. The precipitated nano-catalyst was
separated magnetically, washed with water until the pH
reached 7, and then dried under a vacuum at 60 °C for 2 h.
catalyst was successfully examined in the synthesis of
pyrimido[4,5-b]quinolines via three-component reaction in
H2O as the solvent under reflux conditions with fairly high
yields. This method has some advantages including low
catalyst amounts of Fe3O4, heterogeneous recyclable cat-
alyst with natural base and H2O as the solvent. The work-
up procedure is very simple, and the products do not
require further purification. The simplicity of the present
route and environmental-friendly reaction conditions make
it an interesting alternative to other approaches.
Representative procedure: 1,3,8,8-tetramethyl-5-
phenyl-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-
2,4,6(1H,3H,7H)-trione (4a)
To a magnetically stirred solution of 0.11 g benzaldehyde
(1.00 mmol), 0.07 g dimedone (1.00 mmol), and 0.16 g
6-amino-1,3-dimethyluracil (3, 1.00 mmol) in 10 cm3
H2O, 0.04 g Fe3O4NPs-cell was added and the reaction
mixture was refluxed for 2 h. Upon completion (monitored
Experimental
The chemicals used in this work were purchased from
Merck and Fluka chemical companies. Melting points were
123

L. Edjlali et al.
7. Thakkar KC, Berthel SJ, Cheung AWH, Kim K, Li S, Yun W
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(2007) Chem Abstr 146:184481
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Y (2010) Org Biomol Chem 8:2164
by TLC), the reaction mixture was cooled to room tem-
perature and H2O was evaporated under reduced pressure.
Addition of 5 cm3 acetone to the reaction vessel provided a
colloidal mixture from which Fe3O4NPs-cell was separated
using external magnet. Finally, 6 cm3 n-hexane was added
dropwise to the vessel and 4a was separated as a pure solid
product with filtration.
10. Khattab AF, Kappe T (1996) Monatsh Chem 127:917
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Acknowledgments We gratefully acknowledge financial support
from the Research Council of Tabriz Branch of Islamic Azad
University.
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