Magnetic graphene oxide anchored sulfonic acid as a novel nanocatalyst for the synthesis of N-aryl-2-amino-1,6-naphthyridines

Article abstract of DOI:10.1002/jccs.201300167

Magnetic graphene oxide functionalized with sulfonic acid (Fe ₃O₄-GO-SO₃H) was used as a new recyclable nanocatalyst for one-pot synthesis of N-aryl-2-amino-1,6-naphthyridine derivatives under solvent free conditions. The catalyst could be easily recovered from the reaction mixture by an external magnet and reused without significant decrease in activity even after 4 runs. This nanocatalyst exhibited better activities to other commercially available sulfonic acid catalysts.

Full text of DOI:10.1002/jccs.201300167

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Magnetic Graphene Oxide Anchored Sulfonic Acid as a Novel Nanocatalyst for the
Synthesis of N-aryl-2-amino-1,6-naphthyridines
Shahnaz Rostamizadeh,a* Mina Rezgi,a Nasrin Shadjoub and Mohammad Hasanzadehc
aDepartment of Chemistry, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran
bEnzyme Technology Lab., Biochemistry Dept., Genetic and Metabolism Group, Pasteur Institute of Iran,
P.O. Box 13164, Tehran, Iran
cDrug Applied Research Center, Tabriz University of Medical Science, Tabriz 51664, Iran
(Received: Mar. 31, 2013; Accepted: Jun. 27, 2013; Published Online: ??; DOI: 10.1002/jccs.201300167)
Magnetic graphene oxide functionalized with sulfonic acid (Fe3O4-GO-SO3H) was used as a new recycla-
ble nanocatalyst for one-pot synthesis of N-aryl-2-amino-1,6-naphthyridine derivatives under solvent
free conditions. The catalyst could be easily recovered from the reaction mixture by an external magnet
and reused without significant decrease in activity even after 4 runs. This nanocatalyst exhibited better ac-
tivities to other commercially available sulfonic acid catalysts.
Keywords: Magnetic nanocatalyst; Sulfonic acid; N-aryl-2-amino-1,6-naphthyridines.
INTRODUCTION
Acid catalysts are used in a variety of industrial or-
Scheme I Preparation of (Fe3O4)-GO-SO3H
ganic reactions, including aldol condensations, acylations,
nucleophilic additions, hydrolyses, and others. However,
use of soluble or liquid acids (homogeneous catalysts) has
been inhibited in manufacturing synthesis because of diffi-
culty in their waste neutralization, separations, reactor cor-
rosion, and reusability. Consequently, the need for solid
acid catalysts has arisen.1
GO, as a basic material for the preparation of individ-
ual graphene sheets in bulk-quantity, has attracted great at-
tention in recent years.2-4 In addition, the very large spe-
cific surface area, the abundant oxygen containing surface
functionalities, such as epoxide, hydroxyl, and carboxylic
groups, and the high water solubility afford GO sheets
great promise for many more applications.2,3 For instance,
the GO nano-sheets modified with polyethylene glycol
have been employed as aqueous compatible carriers for
water-insoluble drug delivery.2 The intrinsic oxygen-con-
taining functional groups were used as initial sites for de-
position of metal nanoparticles, such as Fe3O4, on the GO
sheets, which opened up a novel route to multifunctional
nanometer scaled catalytic, magnetic, and electronic mate-
rials.5-8
acid catalyst for the synthesis of N-aryl-2-amino-1,6-naph-
thyridine derivatives.
It should be noted that [(Fe3O4)-GO-SO3H] exhibits
much better catalytic properties (activity and recyclability)
than porous solid acids such as -SO3H functionalized or-
dered mesoporous silica and other -SO3H functionalized
nanoparticles (Fe3O4) in acid-catalyzed reactions. This ac-
However, there are no reports about the function-
alization of magnetic graphene oxide with sulfonic acid
groups. Hence, for the first time the present work illustrates
the immobilization of sulfonic acid groups on magnetic
graphene oxide (Scheme I) for its use as recyclable, solid
* Corresponding author. Fax: +98(21)22853650; Email: rostamizadeh@kntu.ac.ir, shrostamizadeh@yahoo.com
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Article
Rostamizadeh et al.
from the diffraction GO on its (002) layer planes. Also,
synthetic nanocatalyst showed some low intensity diffrac-
tion peaks that were indexed to cubic Fe3O4. In general, the
XRD peaks of nanocatalyst were indexed to (002), (311),
(400), (422) and (511) planes of a cubic unit cell of magne-
tite, appearing at 34.90°, 45.53°, 56.21°, 64.01° and 67.29°,
respectively.
tive solid acid catalyst in the presence of a magnetic field
was easily recovered and exhibited good recyclability.
Over the past few years, naphthyridine derivatives
have received considerable attention because of their wide
range of biological and pharmaceutical activities, such as
antitumor, anti-inflammatory, and antifungal properties.9-11
These compounds are very useful in the treatment of hyper-
tension, myocardial infarction, hyperlipidemia, cardiac ar-
rhythmia, and rheumatoid arthritis.12-14
Also the SEM (Fig. 3) showed that the embedded
nanoparticles were presented as uniform particles with rod
morphology.
In view of these useful properties, and since we were
interested in the synthesis of N-aryl-2-amino-1,6-naph-
thyridine derivatives, a literature survey revealed that there
are only a few reports for the synthesis of these compounds.
El-Subbagh et al. have reported the synthesis of 1,6-naph-
thyridine derivatives through the two component reaction
of a,b-unsaturated ketones and cyanoacetamide in bu-
tanol.10 Recently, Shu-Jiang Tu et al.15 reported the synthe-
sis of N-aryl-2-amino-1,6-naphthyridine derivatives through
three component reaction between a,b-unsaturated ke-
tones, aniline, and malononitrile using microwave irradia-
tion in the presence of acetic acid as catalyst.
At first, for optimization of the reaction conditions,
3,5-bis(4-chlorobenzylidene)-1-methylpiperidin-4-one
However, these methods are time-consuming and use
large amount of toxic solvents, and reagents. Thus, the de-
velopment of a green, simple, efficient, and general method
for the synthesis of these widely used organic compounds,
from readily available reagents, remains one of the major
challenges in organic synthesis.
Fig. 1. The IR spectra of (Fe3O4)-GO-SO3H.
Therefore in this work, magnetically recoverable cat-
alyst [(Fe3O4)-GO-SO3H] have been used as new acidic
catalyst for the one-pot synthesis of N-aryl-2-amino-1,6-
naphthyridine derivatives under solvent free conditions.
RESULTS AND DISCUSSION
At first the (Fe3O4)-GO was prepared according to the
reported method in the literature with some modifica-
tions.16 Then, the magnetic graphene oxide was reacted
with chlorosulfonic acid to prepare the (Fe3O4-GO-SO3H)
as a new nanocatalyst. The prepared (Fe3O4)-GO-SO3H
was characterized with SEM, IR, XRD and acid-base titra-
tion.
Fig. 2. The XRD patterns of (Fe3O4)-GO-SO3H.
In FT-IR spectra the band in the region of 1036 and
1153 cm-1 is attributed to the stretching vibrations of the
(S=O) and the peak appeared at about 3367 cm-1 is due to
the stretching of OH groups in the SO3H (Fig. 1).
The structural properties of the synthesized nanocat-
alyst were analyzed by XRD (Fig. 2). (Fe3O4)-GO-SO3H
showed a sharp diffraction peak at 34.90° which originated
Fig. 3. The SEM image of (Fe3O4)-GO-SO3H.
2
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JOURNAL OF THE CHINESE
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Fe2O3-GO for Synthesis of Naphthyridines
Table 1. Comparing the efficiency of different catalysts in the
(0.33 mmol), aniline (0.33 mmol), and malononitrile (0.33
mmole) were used as model reactants under solvent-free
conditions (Scheme II).
synthesis of 6d
Entry
Catalyst*
Time (min) Yield (%)
1
No catalyst
H3PW12O40
180
180
180
180
240
300
360
5
Trace
45
2
Scheme II Model reaction for the optimization
3
HClO4/SiO2
50
4
NaHSO4/SiO2
47
5
NaHSO4
35
6
CuO NPs
Trace
Trace
96 15
Trace
Trace
95 17
96
7
Fe3O4 NPs
8
Acetic acid, MW, 110 ºC, 200W
MCM-41
9
180
180
130
61
10
11
12
(a-Fe2O3)-MCM-41
(a-Fe2O3)-MCM-41-SO3H
(Fe3O4)-GO-SO3H
In order to show the unique catalytic behavior of
(Fe3O4)-GO-SO3H and to compare its activity with other
catalysts, this reaction was performed in the presence of
catalytic amount of H3PW12O40, HClO4/SiO2, NaHSO4/
SiO2, NaHSO4, MCM-41, (a-Fe2O3)-MCM-41, (a-Fe2O3)-
MCM-41-SO3H and nanocrystalline metal oxides such as
CuO and Fe3O4 nanoparticles. It was observed that only
acidic catalysts were able to catalyze this reaction. Hence,
it seems that the (Fe3O4)-GO-SO3H is the most effective
catalyst for this purpose, leading to the synthesis of N-
aryl-2-amino-1,6-naphthyridine derivatives in higher yields
and shorter reaction times. The efficiency of this catalyst is
due to the high surface area and strong acidity of -SO3H
groups (Table 1).
* Catalytic amount of all compared catalysts is 50 mg per 0.33
mmol of reactants
Table 2. Solvent screening for the synthesis of 6d
Reaction
Entry
Solvent
Time (min) Yield (%)
condition
1
2
3
4
5
6
DMF
CH3CN
CH3OH
C2H5OH
H2O
reflux
reflux
180
180
180
180
180
61
75
50
10
60
-
reflux
reflux
reflux
-
Solvent-free
96
A comparison of the performance of the (Fe3O4)-GO-
SO3H in various solvents is shown in Table 2. Among the
solvents tested (DMF, acetonitrile, methanol, ethanol, wa-
ter) and solvent-free conditions the latter gave the highest
yields with shorter reaction times.
A plausible mechanism for the synthesis
of N-aryl-2-amino-1,6-naphthyridine in
the presence of (Fe3O4)-GO-SO3H
Scheme III
After optimization of the reaction condition, a variety
of aromatic aldehydes, possessing both electron-donating
and electron-withdrawing groups were employed for N-
aryl-2-amino-1,6-naphthyridine formation and the results
indicated that for 3,5-dibenzylidenepiperidin-4-one bear-
ing different functional groups, the reaction proceeded
smoothly in all cases. It is worthwhile to note that 3,5-di-
benzylidenepiperidin-4-one with electron-withdrawing
groups reacted rapidly whereas those with electron-rich
groups, required longer reaction times. Electron-withdraw-
ing groups on the phenyl rings induce greater electronic
positive charge on the corresponding b-atoms than electron
donating moieties (Table 3).
The plausible mechanism is shown in Scheme III. Be-
cause of high surface area of magnetic nanocatalyst, the re-
actants are absorbed easily toward the nanocatalyst, and ac-
companied by the inherent Brönsted acidity of -SO3H and
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Rostamizadeh et al.
Table 3. The reaction time (min) and the yield (%) of N-aryl-2-amino-1,6-naphthyridine product
M.P (ïC)
Time
Yield* (%)
M.P (ïC)
Reported
Entry
Product
(min)
Found
HN
N
CN
Cl
Cl
1
6a
35
95
221-223
-
Cl
Cl
N
HN
N
CN
Cl
Cl
2
3
4
5
6
6b
6c
6d
6e
6f
26
56
61
65
60
95
93
96
84
87
239-240
244-245
254-255
233-235
229-231
-
N
Cl
Cl
HN
N
CN
244-246 15
253-255 15
233-235 15
229-231 15
F
N
F
HN
N
CN
Cl
N
Cl
HN
N
CN
H3C
N
CH3
HN
N
CN
N
HN
N
CN
7
8
9
6g
6h
6i
45
50
50
96
90
93
243-245
243-245
268-269
243-245 15
O2
N
N
NO2
HN
N
CN
244-247 15
O2
N
NO2
N
HN
N
CN
268-270 15
Br
N
Br
4
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Fe2O3-GO for Synthesis of Naphthyridines
Lewis acidity of the Fe3+, which both are capable of bond-
ing with the carbonyl oxygen of the 3,5-dibenzylidene-
piperidin-4-one moiety. Afterwards, the Michael addition
between activated 3,5-dibenzylidenepiperidin-4-one (1)
and malononitrile (2) occurs, and then nucleophilic addi-
tion of aniline (3) to one of the cyano groups in the interme-
diate (4) results in the formation of the intermediate (5).
Subsequently, through cyclization, and aromatization, the
product (6) is formed. In other words, ionic intermediates
(4, 5) are generated inside the nanocatalyst because of the
strong polarity of the –SO3H and Fe3+ groups. Using this
magnetic nanocatalyst, the reaction rates and yields under
the reaction condition are enhanced.
for more 30 min until HCl was removed from reaction vessel. The
mixture was then filtered and washed with CH2Cl2 to give
(Fe3O4)-GO-SO3H as brown powder.
General Procedure for the synthesis of 3,5-dibenzyl-
idenepiperidin-4-one.10 In a 50-mL reaction vial, a mixture of
the 4-piperidone (10 mmol), the appropriate aldehyde (20 mmol),
10% NaOH (1 mL) and 95% EtOH (30 mL) was stirred at room
temperature for 0.5-2 h. The separated solid was collected by fil-
tration and recrystallized from ethanol for further purification.
General Procedure for the synthesis of N-aryl-2-amino-
1,6-naphthyridine derivatives. To the mixture of 3,5-dibenzyl-
idenepiperidin-4-one (0.33 mmol), aniline (0.33 mmol), and
malononitrile (0.33 mmol) was added (Fe3O4)-GO-SO3H (50
mg); it was then stirred at 80 °C for an appropriate period of time
(Table 3). After completion of the reaction (monitored by thin-
layer chromatography, TLC; petroleum ether and EtOAc, 1:1),
the ethanol was added to the reaction mixture and the catalyst was
collected with an external magnet. Then, the mixture was filtered
and the product was further purified by recrystallization from
EtOH/H2O (1:1) to give the pure product.
Finally, because of the magnetic property of the cata-
lyst and in the presence of an external magnet, catalyst was
transferred onto the magnet steadily and the reaction mix-
ture turned clear within 10 s. Thus, the catalyst was col-
lected effectively and the recovered catalyst was used in
subsequent runs without observation of any significant de-
crease in activity even after 4 runs (Fig. 4).
CONCLUSIONS
EXPERIMENTAL
In summary, the new (Fe3O4)-GO-SO3H nanocatalyst
was prepared directly through the reaction of chlorosul-
fonic acid with (Fe3O4)-GO and used as a magnetically re-
coverable catalyst for an efficient one-pot synthesis of
N-aryl-2-amino-1,6-naphthyridine derivatives under sol-
vent free conditions. The catalyst was separated with an ex-
ternal magnet, and used in subsequent runs without obser-
vation of significant decrease in activity even after 3 runs.
This new prepared catalyst exhibited better activities to
other commercially available sulfonic acid catalysts.
Melting points were recorded on a Buchi B-540 apparatus.
IR spectra were recorded on an ABB Bomem Model FTLA200-
1
100 instrument. H and 13CNMR spectra were measured on a
Bruker DRX-300 spectrometer, at 300 and 75 MHz, using TMS as
an internal standard. Chemical shifts (d) were reported relative to
TMS, and coupling constants (J) were reported in hertz (Hz).
Mass spectra were recorded on a Shimadzu QP 1100 EX mass
spectrometer with 70-eV ionization potential. X-ray powder dif-
fraction (XRD) was carried out on a Philips X’Pert diffractometer
with CoKa radiation.
Preparation of (Fe3O4)-GO-SO3H. To (Fe3O4)-GO (1 g),
chlorosulfonic acid (0.5 g, 4.5 mmol) in 5 mL dichloromethane
was added dropwise at room temperature during 30 min. After
completion of the addition, the mixture was mechanically stirred
ACKNOWLEDGEMENTS
We gratefully acknowledge the support of this work
to K. N. Toosi University of Technology.
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