γ-Fe2O3@SiO2-γ-aminobutyric acid as a novel superparamagnetic nanocatalyst promoted green synthesis of chromeno[4,3,2-de][1,6]naphthyridine derivatives

Article abstract of DOI:10.1007/s00706-018-2317-5

Abstract: Grafting of γ-aminobutyric acid on the superparamagnetic γ-Fe₂O₃@SiO₂ nanoparticles afforded γ-Fe₂O₃@SiO₂-γ-aminobutyric acid as a novel heterogeneous nanocatalyst, which was char

Full text of DOI:10.1007/s00706-018-2317-5

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-018-2317-5
ORIGINAL PAPER
γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic
nanocatalyst promoted green synthesis of chromeno[4,3,2‑de][1,6]‑
naphthyridine derivatives
Hadi Mohammadi1 · Hamid Reza Shaterian1
Received: 22 June 2018 / Accepted: 10 October 2018
© Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract
Grafting of γ-aminobutyric acid on the superparamagnetic γ-Fe2O3@SiO2 nanoparticles aforded γ-Fe2O3@SiO2-γ-
aminobutyric acid as a novel heterogeneous nanocatalyst, which was characterized by X-ray difraction, Fourier transform-
infrared spectroscopy, vibrating sample magnetometry, feld emission scanning electron microscopy, energy-dispersive
X-ray spectroscopy, and thermal analysis. In this research, we report a convenient and one-pot efcient direct protocol for the
pseudo four-component preparation of chromeno[4,3,2-de][1,6]naphthyridine derivatives via cascade condensation reaction
of malononitrile, 2,4-dihydroxyacetophenone with various aromatic aldehydes in the presence of the catalytic amount of
the γ-Fe2O3@SiO2-γ-aminobutyric acid under green conditions in aqueous media. This procedure ofers several advantages
such as: very easy reaction conditions, simple work-up, or purifcation, excellent yields, high purity of the desired product,
atom economy, and short reaction times. The superparamagnetic nanocatalyst is magnetically separable and kept stability
after recycling for at least fve consecutive runs without detectable activity loss.
Graphical abstract
Keywords γ-Fe2O3@SiO2-γ-aminobutyric acid · Superparamagnetic nanocatalyst · Chromeno[4,3,2-de][1,6]-
naphthyridines · Multi-component reactions · Water
Introduction
The fields of organometallic compounds with the wide
variety of structures have been high-fast developing in the
chemistry [1–4]. Nano-superparamagnetic organometallic
compounds are considered as a very important class of
materials, which have wide broad applications in many
biological aspects [5–8]. Nano-superparamagnetic transi-
tion metal oxides such as iron are one of the most adjust-
able systems which have also applications in medical,
industrial, and biological in addition to their important
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-018-2317-5) contains
supplementary material, which is available to authorized users.
* Hamid Reza Shaterian
hrshaterian@chem.usb.ac.ir
1
Department of Chemistry, Faculty of Sciences, University
of Sistan and Baluchestan, PO Box 98135-674, Zahedan,
Iran
Vol.:(0123456789)
1 3

H. Mohammadi, H. R. Shaterian
roles in catalysis and organic synthesis [9–12]. Studies
of new kind of organometallic compounds grafting of
organocatalysts on the superparamagnetic, γ-Fe2O3@
SiO2, nanoparticles were attracting the consideration
of researchers in organic chemistry [13–16]. In the pre-
sent research, we report preparation of γ-Fe2O3@SiO2-
γ-aminobutyric acid (γ-Fe2O3@SiO2-GABA) for the
first time. This superparamagnetic organometallic com-
pound as catalyst was applied for synthesis a series of
chromeno[4,3,2-de][1,6]naphthyridines compounds from
cascade pseudo four-component condensation reaction of
malononitrile, 2,4-dihydroxyacetophenone with various
aromatic aldehydes (Scheme 1).
Results and discussion
γ-Fe2O3@SiO2-GABA as a new nanocatalyst was synthesized
based on the following procedure (Scheme 2). First, super-
paramagnetic Fe3O4 nanoparticles were facilely prepared by
a chemical co-precipitating method [17]. Second, Fe3O4 nano-
particles were converted into γ-Fe2O3 at 300 °C for 3 h. Then,
γ-Fe2O3 was encapsulated by SiO2 as γ-Fe2O3@SiO2 using
tetraethyl orthosilicate (TEOS) [18]. Finally, the reaction of
GABA with γ-Fe2O3@SiO2 formed a superparamagnetic
γ-Fe2O3@SiO2-GABA as the new nanocatalyst.
The magnetic nanocatalyst was characterized using dif-
ferent techniques such as X-ray difraction (XRD), Fourier
transform-infrared spectroscopy (FT-IR), feld emission
scanning electron microscopy (FE-SEM), energy-dispersive
Scheme 1
R
OH
CH3
CHO
N
NC
CN
CN
O
NH2
2
H O, 80
°C
2
HO
H2N
N
O
OH
R
1
2
3
4a-4p
-Fe O @SiO -GABA
NH2
γ
2
3
2
Scheme 2
calcination
300 °C, 3 h
NH3
Fe3O4
-Fe O
3
γ
.
2
.4H
+
2
FeCl3 6H2O
FeCl2 2O
H
2O
TEOS
SiO2
-aminobutyric acid
γ
-Fe O
γ
γ
O
O
-Fe O
g
2
3
2
3
NH2
SiO2
O
O
.
NH2
1 3

γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic nanocatalyst promoted…
X-ray spectroscopy (EDS), vibrating sample magnetometry
(VSM), and thermal analysis (TGA). The XRD patterns of
γ-Fe2O3, γ-Fe2O3@SiO2, and γ-Fe2O3@SiO2-GABA had
six characteristic peaks which have a good accordance with
the cubic structure of maghemite (γ-Fe2O3) (JCPDS fle No
04-0755). The positions of all the peaks indicated retention
of the crystalline structure during functionalization of the
γ-Fe2O3 and the grafting process did not change phase of the
γ-Fe2O3 nanoparticles. The XRD pattern of γ-Fe2O3@SiO2
and γ-Fe2O3@SiO2-GABA showed that SiO2 and GABA
formed amorphous phase which their patterns showed only
pattern of crystalline γ-Fe2O3 nanoparticles (Fig. 1).
We provided FE-SEM image from γ-Fe2O3@SiO2-
GABA. Figure 2a represents the SEM image of γ-Fe2O3@
SiO2-GABA which shows spherical morphology and aver-
age size 13 nm of nanoparticles using histogram curve
Fig. 2b. Superparamagnetic γ-Fe2O3 is encapsulated into
SiO2. It separates organocatalyst by an external magnet and
provides easy work-up; also, SiO2 shell prevents agglomera-
tion (large chunks) of spheres of nanoparticles before and
after the reaction.
nanoparticles size of the catalyst. As it can be observed,
saturation magnetization value of γ-Fe2O3@SiO2-GABA is
57 amu g−1.
The thermal stability of the γ-Fe2O3@SiO2-GABA was
investigated by TGA analysis (Fig. 5). Small weight loss
occurs below 200 °C, which is due to physically adsorbed
solvent and water. There are two exothermic peaks accom-
panied with a mass loss of 7.5% in the temperature range of
200–550 °C in the TGA curve of γ-Fe2O3@SiO2-GABA.
These peaks were mainly attributed to the decomposition
of organic groups (GABA) grafted to the γ-Fe2O3@SiO2
surface. The peak higher than 550 °C most probably corre-
sponds to a phase transition in which the amorphous phase
is converted into a crystalline phase. The total weight loss
was computed to be 7.5% and the amount of GABA loaded
on γ-Fe2O3@SiO2 was equal to 0.72 mmol g−1.
The characterization of γ-Fe2O3@SiO2-GABA as nano-
catalyst was also confrmed by FT-IR spectrum. The peak
at 3400 cm−1 was probably attributed to the NH2 groups,
which is overlapped by the O–H stretching vibration. C–H
stretching vibrations appear at 2930 cm−1. The Fe–O stretch-
ing vibration was observed at 550–650 cm−1 and stretch-
ing mode of Si–O–Si showed a strong broad peak at about
1099–1220 cm−1 (Fig. 6).
The components of the γ-Fe2O3@SiO2-GABA were also
analyzed using energy-dispersive X-ray spectroscopy (EDS).
EDS basically gives elemental information for qualitative
analysis [19]. The EDS spectrum in Fig. 3 implicates the
presence of atoms Fe, O, Si, C, and N in the catalyst which
confrms the structure of organometallic compound.
The VSM diagram shows the magnetic properties of syn-
thesis catalyst (Fig. 4). The hysteresis loop of the γ-Fe2O3@
SiO2-GABA was measured. Magnetization (emu g−1) as a
function of applied feld (Oe) was depicted in Fig. 4 with the
confned feld from −10,000 to +10,000 Oe. Superparamag-
netic behavior of the γ-Fe2O3@SiO2-GABA illustrates small
To evaluate the activity of the catalyst, the pseudo four-
component reaction of 2,4-dihydroxyacetephenone, malon-
onitrile, and benzaldehyde was selected as a model to opti-
mize the reaction conditions (Scheme 3).
The reaction was carried out in the presence of γ-Fe2O3@
SiO2-GABA, Fe3O4 NMPs, γ-Fe2O3, γ-Fe2O3@SiO2, citric
acid, sulfamic acid, InCl3, GABA, silica gel, and FeCl3·6H2O
at 80 °C in aqueous media. The results are summarized in
Table 1. With regard to the results in Table 1, it was observed
that nano-catalysts have shown better conditions than other
types of catalysts in the preparation of chromeno[4,3,2-de]-
[1,6]naphthyridine derivatives. Table 1 also shows that
sequence activities of various nano-catalysts are γ-Fe2O3@
SiO2-GABA > γ-Fe2O3@SiO2 > γ-Fe2O3 > Fe3O4. GABA
as catalyst showed the catalytic activity for this reaction
but moderate yields and no reusability of GABA are dis-
advantages of it. γ-Fe2O3@SiO2-GABA nanocatalyst has
several advantages in the synthesis of chromeno[4,3,2-de]-
[1,6]naphthyridine derivatives, such as good yields, short
reaction times, less amount of the catalyst, and excellent
reusability (Table 1).
To select the appropriate solvent, various solvents such as
CH2Cl2, CH3CN, ethanol, water, mixtures of water:ethanol,
and also under solvent-free conditions, were used in the
model reaction in the presence of γ-Fe2O3@SiO2-GABA
(7 mg). The results are shown in Table 2. According to the
results, the highest yield of product and maximum perfor-
mance of the catalyst were obtained, once the reaction was
carried out in water as a solvent. The reaction completed
Fig. 1 XRD pattern of a γ-Fe2O3; b γ-Fe2O3@SiO2; c γ-Fe2O3@
SiO2-GABA
1 3

H. Mohammadi, H. R. Shaterian
Fig. 2 a FE-SEM image of MNPs-GABA; b particle size distribution histogram of γ-Fe2O3@SiO2-GABA
in 50 min and excellent yield (92%) of the product was
obtained in water (Table 2, entry 5). The important role of
performance of the catalyst in water was the formation of
hydrogen bonds between starting materials and water. A
signifcant decrease in yields was observed when CH2Cl2,
CH3CN, ethanol were used as the organic reaction solvent.
Moreover, reaction performed was drastically decreased with
further increase in ethanol in water (Table 2, entries 6, 7).
To optimize the amount of the γ-Fe2O3@SiO2-GABA as
catalyst in the reaction model, the reaction was carried out
in presence of the various amounts of the catalyst at 80 °C
in water as solvent (Table 3, entries 1–5). The use of 7 mg
of the catalyst in the reaction is sufcient for achieving the
best yield of the desired product. For selecting the best tem-
perature, the reaction was performed at diferent tempera-
tures (Table 3, entries 3, 6–8) in the presence of γ-Fe2O3@
1 3

γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic nanocatalyst promoted…
Fig. 6 FT-IR spectra: (a) GABA; (b) γ-Fe2O3@SiO2; (c) γ-Fe2O3@
SiO2-GABA
Fig. 3 EDS spectrum of γ-Fe2O3@SiO2-GABA
SiO2-GABA (7 mg) in water. The best result was obtained
at 80 °C (Table 3, entry 3).
According to optimal considered conditions (7 mg
γ-Fe2O3@SiO2-GABA, reaction temperature 80 °C in water
as green solvent), some new chromeno[4,3,2-de][1,6]naph-
thyridine derivatives were synthesized and results are shown
in Table 4. The obtained results indicate that the reactions
can proceed well enough with a relatively wide range of
aromatic-substituted benzaldehydes containing electron-
donating and electron-withdrawing groups.
According to the literature [21], the proposed mecha-
nism for the formation of the product is shown in Scheme 4.
First, chalcone I was formed through the aldol condensation
between benzaldehydes 3 and 2,4-dihydroxyacetophenone
(2). Next, Knoevenagel product II was obtained from the
reaction of malononitrile with chalcone I. In the following,
the intramolecular nucleophilic attack by the enolic OH
group of II leads to formation of the intermediate III. The
condensation reaction of III with second molecule of malo-
nonitrile produces the intermediate IV. Subsequently, the
intramolecular cyclization of IV followed by aromatization
formed the fnal product.
Fig. 4 VSM diagrams of γ-Fe2O3@SiO2-GABA
GABA as organocatalyst can be separated easily by an
external magnet when it supports on superparamagnetic of
γ-Fe2O3 nanoparticles. GABA bonded to γ-Fe2O3@SiO2
from carboxylic acid side and amino group acts as basic
catalyst. γ-Fe2O3@SiO2-GABA provides a simple work-up
that causes high yields of isolated pure products. Superpara-
magnetic γ-Fe2O3 is encapsulated into SiO2. γ-Fe2O3@SiO2-
GABA as a heterogenous basic nanocatalyst acts well in the
reactions and produces desired products in high yields after
purifcation by a simple work-up.
As shown in Fig. 7, γ-Fe2O3@SiO2-GABA can act as an
efective catalyst with respect to the reaction time, yield of
the product, TON (turnover number) and TOF (turnover fre-
quency) and the recyclability of γ-Fe2O3@SiO2-GABA was
Fig. 5 Thermogravimetric analysis of γ-Fe2O3@SiO2-GABA
1 3

H. Mohammadi, H. R. Shaterian
Scheme 3
OH
CH3
CHO
N
N
NC
CN
O
NH2
2
CN
HO
H2N
O
OH
1
2
3
4a
-Fe O @SiO -GABA
γ
NH2
2
3
2
Table 3 Optimization conditions of the amount of the catalyst and
also selecting the best temperature for the preparation of 5-amino-9-
hydroxy-2-phenylchromeno[4,3,2-de][1,6]naphthyridine-4-carboni-
trile in aqueous media
Table 1 Preparation of 5-amino-9-hydroxy-2-phenylchromeno[4,3,2-
de][1,6]naphthyridine-4-carbonitrile in the presence of γ-Fe2O3@
SiO2-GABA, Fe3O4NMPs, γ-Fe2O3, γ-Fe2O3@SiO2, citric acid,
sulfamic acid, InCl3, GABA, silica gel, and FeCl3·6H2O at 80 °C in
aqueous media
Entry
Catalyst/mg
Temperature/°C
Time/min
Yield/%a
Entry
Catalyst (amount) [Ref.]
Time/h
Yield/%a
1
2
3
4
5
6
7
8
3
5
7
9
11
7
80
80
80
80
80
60
70
90
70
70
50
50
50
70
60
50
75
82
92
92
89
73
83
92
1
2
3
4
5
6
7
8
FeCl3·6H2O (18 mg)
Fe3O4 NMPs (12 mg) [22]
GABA (35 mg)
γ-Fe2O3 NMPs (11 mg)
γ-Fe2O3@SiO2 NMPs (10 mg)
γ-Fe2O3@SiO2-GABA (7 mg)
Silica gel (30 mg) [21]
InCl3 (22 mg)
4
4
4
4
2
0.83
2
4
4
35
60
45
65
75
92
67
50
55
50
35
7
7
Reaction conditions: benzaldehyde (1 mmol), malononitrile
(2 mmol), and 2,4-dihydroxyacetephenone (1 mmol)
9
10
11
Sulfamic acid (25 mg)
Citric acid (60 mg)
–
4
9
aYields refer to isolated pure product
Reaction conditions: benzaldehyde (1 mmol), malononitrile
(2 mmol), and 2,4-dihydroxyacetephenone (1 mmol) in the presence
of diferent catalysts at 80 °C in water as solvent
examined in the one-pot pseudo four-component synthesis
of 5-amino-9-hydroxy-2-phenylchromeno[4,3,2-de][1,6]-
naphthyridine-4-carbonitrile under optimized conditions
(Fig. 7). After completion of reaction, the reaction mixture
was cooled to room temperature and the solid separated was
fltered, ethanol was added to the reaction mixture and the
γ-Fe2O3@SiO2-GABA was separated by external magnet.
The catalyst was washed with ethanol for three times and
dried. As it was shown in Fig. 7, at least even after fve
runs, catalytic activity and product yield have no signifcant
loss. Thus, this catalyst can endure reaction conditions and
remain stable.
aYields refer to isolated pure product
Table 2 Preparation of 5-amino-9-hydroxy-2-phenylchromeno[4,3,2-
de][1,6]naphthyridine-4-carbonitrile in the presence of γ-Fe2O3@
SiO2-GABA (7 mg) in diferent solvents
Entry Solvent
Time/min Temperature/°C Yield/%a
1
2
3
4
5
6
7
8
EtOH
CH3CN
CH2Cl2
Neat (solvent-free)
H2O
H2O: EtOH (50:50) 50
H2O: EtOH (30:70) 50
H2O: EtOH (70:30) 50
80
110
120
50
80
80
40
90
80
80
80
80
60
45
15
70
92
75
70
80
50
Conclusion
γ-Fe2O3@SiO2-GABA as a novel organometallic hetero-
geneous nano-magnetic catalyst has been successfully
synthesized and characterized by the several techniques
such as XRD, FT-IR, VSM, FE-SEM, EDS, and TGA-
DTG. This efficient nano-organometallic catalyst was
Reaction conditions: benzaldehyde (1 mmol), malononitrile
(2 mmol), and 2,4-dihydroxyacetephenone (1 mmol) in the presence
of γ-Fe2O3@SiO2-GABA (7 mg) as catalyst
aYields refer to isolated pure product
1 3

γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic nanocatalyst promoted…
Table 4 Synthesis of
Entry
R
Product Time/min Yield/%a TONb
TOFc/h−1
Observed m.p./°C Lit. m.p./°C
chromeno[4,3,2-de][1,6]-
naphthyridine derivatives
catalyzed by γ-Fe2O3@SiO2-
GABA nanoparticles (7 mg) at
80 °C in water as green solvent
(Scheme 1)
1
H
4a
4b
4c
4d
4e
4f
50
45
45
50
50
55
55
55
50
50
50
55
60
60
60
60
92
93
93
92
92
90
90
90
90
91
90
89
89
87
86
89
184
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300 [20]
221
2
4-Me
4-MeO
2-Me
3-Me
2-Cl
186
>300 [20]
248
3
186
248
>300 [21]
4
184
–
–
–
–
–
–
–
–
–
–
–
–
–
221
5
184
221
6
180
197
7
2-Br
4g
4h
4i
180
197
8
4-Br
180
197
9
4-Cl
180
216
10
11
12
13
14
15
16
3-Br
4j
182
219
2-MeO
2,3-(MeO)2
4k
4l
180
216
178
195
3,4,5-(MeO)3 4m
178
178
3,4-(MeO)2
2,5-(MeO)2
3,4-(HO)2
4n
4o
4p
174
174
172
172
178
178
Reaction conditions: substituted benzaldehydes (1 mmol), malononitrile (2 mmol), 2,4-dihydroxyacetophe-
none (1 mmol) in 3 cm3 water and 7 mg of the catalyst (γ-Fe2O3@SiO2-GABA)
aYields refer to the isolated pure products
bTON (Turnover number)=mmol of desired product/mmol of GABA in the used catalyst. The mmol
of –NH2 group was equal to the mmol GABA which were loaded on γ-Fe2O3@SiO2. It was equal to
0.72 mmol g−1 (calculated by TGA analysis)
cTOF (Turnover frequency)=TON/reaction time (h)
successfully used for the pseudo four-component prepa-
ration of chromeno[4,3,2-de][1,6]naphthyridine deriva-
tives under green conditions in aqueous media. Easy
reaction conditions, simple work-up, or purification,
excellent yields, high purity of the desired product, atom
economy, and short reaction times are some advantages
of this protocol. The superparamagnetic nanocatalyst is
magnetically separable and stable in the reaction condi-
tions without detectable activity loss.
Experimental
All materials were purchased from Merck and Aldrich
company. The NMR spectra were provided on Bruker
Avance 300 MHz instruments in DMSO-d6 as deuterated
solvents. Melting points were determined in open capillar-
ies using a BUCHI510 melting point apparatus. Thin-layer
chromatography (TLC) was performed on silica-gel Poly
1 3

H. Mohammadi, H. R. Shaterian
R
Scheme 4
NH2
O
H
C
N
H
H2
CN
HO
OH
O
H2N
2
R
O
HO
O
N
NH2
3
VI
H2N
HO
OH
Aromatization
-H2O
NH
NC
O
C
N
R
NH
I
HO
OH
R
O
V
H2N
H
H
OH
NC
NC
CN
1
CN
H2N
NC
NH2
-H2O
NC
N
C
N
C
N
NH2
OH
R
O
R
IV
II
NC
CN
C
OH
CN
CN
HN
H
OH
O
H
H2N
N
NC
CN
OH
III
R
-Fe2O3@SiO2-GABA
γ
NH2
=
Gram SIL G/UV 254 plates and progress of reactions was
monitored by TLC. FT-IR spectra were recorded using
KBr disks on a JASCO FT-IR 460 plus spectrophotom-
eter. Elemental compositions were determined with a Leo
1450 VP scanning electron microscope equipped with an
SC7620 energy-dispersive spectrometer (SEM-EDS) pre-
senting a 133-eV resolution at 20 kV. Power X-ray difrac-
tion (XRD) was performed on a Bruker D8-advance X-ray
difractometer with Cu Kα (λ = 0.154 nm) radiation. The
magnetic property was measured by VSM/AGFM. TGA
was done on a thermal analyzer with a heating rate of
10 °C min−1 over a temperature range of 25–800 °C under
fowing compressed N2.
Preparation of GABA grafting γ‑Fe2O3@SiO2
magnetic nanoparticles
Preparation of γ‑Fe2O3
The Fe3O4 nanoparticles were prepared by literature proce-
dure [17, 18]. FeCl2∙4H2O (1.25 g, 6.28 mmol) and 3.33 g
1 3

γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic nanocatalyst promoted…
Run
Product yield/%a
Time/min
TON
TOF/h-1
Product yield/%
Catalyst yield/%
Fig. 7 Reusability of γ-Fe2O3@SiO2-GABA
FeCl3·6H2O (12.30 mmol) were dissolved in 80 cm3 water
separately, followed by the two iron salt solutions being
mixed under continuous stirring (800 rpm). Then, 70 cm3
aqueous ammonia solution (25%) was added dropwise to
the stirring mixture at room temperature for 3 h and stirring
continued for another hour. The black formed products as
Fe3O4 NMPs were collected by an external magnet. They
were washed three times with water and ethanol and dried
at 60 °C for 12 h. Fe3O4 nanoparticles were heated at 300 °C
in a furnace for 3 h. They were then converted into γ-Fe2O3
nanoparticles.
General procedure for the direct synthesis
chromeno[1,6]naphthyridine derivatives using
γ‑Fe2O3@SiO2‑GABA nanoparticles as catalyst
Fe2O3@SiO2-GABA NMPs (7 mg) was added to a mixture
of 2,4-dihydroxyacetephenone (1 mmol), malononitrile
(2 mmol), and aromatic aldehydes (1 mmol) in 3 cm3 water.
The reaction mixture was stirred at 80 °C in an oil bath. The
reaction was monitored by TLC. After completion of reac-
tion, the reaction mixture was cooled to room temperature
and the solid separated was fltered, and dissolved in ethanol
to remove the catalyst by an external magnet and purifed
by crystallization in EtOH: DMF (10:1). The pure known
products 4a–4c were characterized and their physical data
were compared with those of known compounds.
Preparation of γ‑Fe2O3@SiO2
γ-Fe2O3 nanoparticles (1 g) were dispersed in 40 cm3 etha-
nol and the resulting mixture was stirred for 1 h at 40 °C.
Subsequently, 2 cm3 tetraethyl orthosilicate (TEOS) was
charged to the reaction vessel and the mixture was continu-
ously stirred for 24 h [18]. The silica-coated nanoparticles
were collected by an external magnet, followed by washing
three times with ethanol and drying at 70 °C in vacuum for
12 h.
5‑Amino‑9‑hydroxy‑2‑(2‑methylphenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4d, C22H14N4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3480, 3338, 3225,
2211 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.66 (1H,
s), 8.18–8.20 (1H, d, J = 8.4 Hz), 7.67 (1H, s), 7.54–7.57
(1H, m), 7.44 (2H, s), 7.31–7.39 (3H, m), 6.81–6.84 (2H,
m), 2.45 (3H, s) ppm; 13C NMR (75 MHz, DMSO-d6):
δ=166.43, 162.41, 162.11, 159.90, 155.68, 153.76, 140.39,
138.94, 136.45, 131.26, 130.07, 129.35, 126.95, 126.33,
117.13, 114.35, 109.13, 107.75, 103.86, 101.70, 76.00,
20.91 ppm.
Preparation of γ‑Fe2O3@SiO2‑GABA nanoparticles
γ-Fe2O3@SiO2 (800 mg) was dispersed in 80 cm3 water
under ultrasonic for 30 min. Subsequently, 1 g GABA was
charged to the reaction vessel and the mixture was continu-
ously stirred for 16 h at 90 °C. γ-Fe2O3@SiO2-GABA nano-
particles were removed from solution reaction by an external
magnet and washed several times with water and ethanol and
dried at 60 °C. The successful synthesis of this superpara-
magnetic nano-heterogenous catalyst was characterized by
several techniques such as XRD, FT-IR, VSM, FE-SEM,
EDS, and TGA analysis. All results confrmed the structure
of the γ-Fe2O3@SiO2-GABA.
5‑Amino‑9‑hydroxy‑2‑(3‑methylphenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4e, C22H14N4O2) Yellow
solid; m.p.: >300 °C; IR (KBr): v=3487, 3328, 3294, 3168,
2206 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.67 (1H,
s), 8.31–8.34 (1H, d, J=8.7 Hz), 8.06–8.14 (3H, m), 7.36–
7.42 (3H, m), 7.32 (1H, s), 6.85–6.88 (1H, d, J =8.7 Hz),
6.30 (1H, s), 2.44 (3H, s) ppm; 13C NMR (75 MHz, DMSO-
d6): δ = 162.44, 162.36, 162.16, 159.80, 155.87, 153.72,
1 3

H. Mohammadi, H. R. Shaterian
139.37, 138.44, 138.25, 131.53, 128.95, 128.54, 127.04,
125.31, 117.10, 114.23, 109.36, 103.99, 103.83, 102.18,
76.10, 21, 65 ppm.
s), 8.50 (1H, s), 8.29–8.32 (2H, d, J=7.2 Hz), 8.07 (2H, s),
7.68–7.71 (1H, d, J=7.8 Hz), 7.45–7.51 (1H, t, J=7.8 Hz),
7.41 (2H, s), 6.82–6.84 (1H, d, J = 8.1 Hz), 6.76 (1H, s)
ppm; 13C NMR (75 MHz, DMSO-d6): δ=162.47, 162.15,
160.37, 159.75, 155.69, 153.70, 140.68, 139.76, 133.47,
131.12, 130.46, 127.17, 126.98, 122.75, 116.98, 114.22,
109.26, 104.08, 103.77, 102.43, 76.05 ppm.
5‑Amino‑9‑hydroxy‑2‑(2‑chlorophenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4f, C21H11ClN4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3461, 3358, 3233,
2210 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.77 (1H,
s), 8.19–8.22 (1H, d, J = 9.0 Hz), 7.76 (1H, s), 7.64–7.68
(2H, m), 7.51–7.57 (3H, m), 7.12 (1H, s), 6.98 (1H, s),
6.92 (1H, s), 6.86–6.89 (1H, m) ppm; 13C NMR (75 MHz,
DMSO-d6): δ = 163.67, 162.59, 162.21, 159.95, 155.87,
153.86, 139.71, 138.88, 131.85, 131.68, 131.09, 130.36,
127.82, 126.94, 117.00, 114.73, 114.51, 108.96, 108.27,
103.92, 102.15, 75.98 ppm.
5 ‑ A m i n o ‑ 9 ‑ h y d r o x y ‑ 2 ‑ ( 2 ‑ m e t h o x y p h e n y l ) ‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile
(4k, C22H14N4O3) Yellow solid; m.p.: >300 °C; IR (KBr):
1
v = 3484, 329, 3160, 2220 cm−1; H NMR (300 MHz,
DMSO-d6): δ=10.68 (1H, s), 7.79–8.08 (3H, q), 7.42–7.51
(3H, m), 7.09–7.22 (2H, m), 6.82–6.88 (2H, m), 3.89 (3H,
s) ppm; 13C NMR (75 MHz, DMSO-d6): δ=162.78, 162.31,
162.07, 159.87, 157.73, 155.94, 153.78, 137.94, 131.60,
131.44, 128.89, 126.51, 121.07, 117.16, 114.44, 112.55,
109.16, 108.58, 103.96, 101.85, 75.98, 56.29 ppm.
5‑Amino‑9‑hydroxy‑2‑(2‑bromophenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4g, C21H11BrN4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3461, 3351, 3228,
2217 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.96 (1H,
s), 8.50 (1H, s), 8.30–8.34 (2H, m), 8.08 (1H, s), 7.68–7.71
(1H, d, J=7.4 Hz), 7.41–7.51 (3H, m), 6.82–6.85 (1H, dd,
J = 12.9, 2.1 Hz), 6.76–6.77 (1H, d, J = 2.1 Hz) ppm; 13C
NMR (75 MHz, DMSO-d6): δ = 162.48, 162.16, 160.39,
159.76, 155.70, 153.71, 140.69, 139.78, 133.48, 131.13,
130.46, 127.18, 126.98, 122.76, 116.98, 114.23, 109.26,
104.04, 103.78, 102.44, 76.10 ppm.
5 ‑ A m i n o ‑ 9 ‑ h y d r ox y ‑ 2 ‑ ( 2 , 3 ‑ d i m e t h ox y p h e n y l ) ‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile
(4l, C23H16N4O4) Yellow solid; m.p.: > 300 °C; IR (KBr):
1
v = 3480, 3338, 3225, 2211 cm−1; H NMR (300 MHz,
DMSO-d6): δ=10.72 (1H, s), 8.11–8.14 (1H, d, J=8.7 Hz),
7.79 (1H, s), 7.74 (2H, s), 7.22–7.30 (3H, m), 6.85–6.91
(2H, m), 3.90 (3H, s), 3.82 (3H, s) ppm; 13C NMR (75 MHz,
DMSO-d6): δ = 163.37, 162.42, 162.13, 159.93, 155.88,
153.82, 153.44, 147.37, 138.57, 134.93, 126.67, 124.51,
122.62, 117.13, 114.53, 114.49, 109.12, 107.94, 103.97,
102.00, 75.97, 21.65 ppm.
5‑Amino‑9‑hydroxy‑2‑(4‑bromophenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4h, C21H11BrN4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3475, 3365, 3156,
2209 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.72 (1H,
s), 8.35 (1H, s), 8.30–8.33 (2H, d, J=8.4 Hz), 8.13 (1H, s),
7.75–7.78 (2H, m), 7.44 (2H, s), 6.86–6.89 (1H, dd, J=12.9,
2.4 Hz), 6.80–6.81 (1H, d, J = 2.4 Hz) ppm; 13C NMR
(75 MHz, DMSO-d6): δ=162.50, 162.19, 161.03, 159.82,
155.84, 153.78, 139.77, 137.60, 132.12, 130.02, 127.16,
124.86, 116.99, 114.32, 109.30, 103.85, 102.86, 76.01 ppm.
5‑Amino ‑9‑hydrox y‑2‑(3,4,5‑trimethox yphenyl)‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile (4m,
C24H18N4O5) Yellow solid; m.p.: > 300 °C; IR (KBr):
v=3382, 3295, 3191, 2297, 2206 cm−1; 1H NMR (300 MHz,
DMSO-d6): δ=10.67 (1H, s), 8.29–8.32 (1H, d, J=8.4 Hz),
7.96 (1H, s), 7.60 (2H, s), 7.36 (2H, s), 6.76–6.87 (3H, m),
3.91 (6H, s), 3.78 (3H, s) ppm; 13C NMR (75 MHz, DMSO-
d6): δ = 162.28, 162.05, 161.55, 159.66, 155.58, 153.65,
153.33, 140.20, 139.20, 133.68, 127.06, 116.95, 114.08,
109.34, 105.48, 103.79, 103.58, 101.96, 76.08, 60.59,
56.40 ppm.
5‑Amino‑9‑hydroxy‑2‑(4‑chlorophenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4i, C21H11ClN4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3461, 3353, 3216,
2210 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.69 (1H,
s), 8.21–8.36 (2H, m), 8.07 (1H, s), 7.40–7.60 (4H, m),
6.77–6.86 (3H, m) ppm; 13C NMR (75 MHz, DMSO-d6):
δ=162.45, 162.15, 161.31, 160.84, 159.74, 155.76, 153.71,
137.18, 135.87, 129.73, 129.11, 128.97, 127.05, 116.79
114.27, 109.25, 103.80, 102.26, 76.05 ppm.
5 ‑ A m i n o ‑ 9 ‑ h y d r ox y ‑ 2 ‑ ( 3 , 4 ‑ d i m e t h ox y p h e n y l ) ‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile (4n,
C23H16N4O4) Yellow solid; m.p.: >300 °C; IR (KBr): v=3459,
3387, 3212, 2295, 2210 cm−1; 1H NMR (300 MHz, DMSO-
d6): δ=10.67 (1H, s), 8.36–8.39 (1H, d, J=8.7 Hz), 7.96–8.06
(3H, m), 7.38 (2H, s), 7.09–7.12 (2H, d, J=8.1 Hz), 6.72–6.97
(2H, m), 3.91 (3H, s), 3.87 (3H, s) ppm; 13C NMR (75 MHz,
DMSO-d6): δ=162.30, 162.11, 161.96, 159.75, 155.85, 153.74,
151.64, 149.18 139.17, 130.94, 127.14, 121.53, 117.09, 114.72,
5‑Amino‑9‑hydroxy‑2‑(3‑bromophenyl)chromeno[4,3,2‑de]‑
[1,6]naphthyridine‑4‑carbonitrile (4j, C21H11BrN4O2) Yel-
low solid; m.p.: >300 °C; IR (KBr): v=3463, 3350, 3229,
2217 cm−1; 1H NMR (300 MHz, DMSO-d6): δ=10.67 (1H,
1 3

γ‑Fe2O3@SiO2‑γ‑aminobutyric acid as a novel superparamagnetic nanocatalyst promoted…
114.18, 111.90, 111.28, 109.45, 103.87, 103.30, 101.81, 76.05,
56.06 ppm.
References
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5 ‑ A m i n o ‑ 9 ‑ h y d r ox y ‑ 2 ‑ ( 2 , 5 ‑ d i m e t h ox y p h e n y l ) ‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile
(4o, C23H16N4O4) Yellow solid; m.p.: >300 °C; IR (KBr):
v=3472, 3318, 3217, 2926, 2226 cm−1; 1H NMR (300 MHz,
DMSO-d6): δ=10.72 (1H, s), 8.08–8.11 (1H, d, J=8.1 Hz),
7.95 (1H, s), 7.42–7.44 (3H, m), 6.85–6.91 (4H, m), 3.85
(3H, s), 3.99 (3H, s) ppm; 13C NMR (75 MHz, DMSO-d6):
δ=162.39, 162.37, 162.08, 159.87, 155.86, 153.82, 153.66,
152.07, 138.15, 129.60, 126.54, 117.06, 116.78, 116.39,
114.51, 114.21, 109.17, 108.45, 104.00, 101.95, 76.10,
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5 ‑ A m i n o ‑ 9 ‑ h y d r o x y ‑ 2 ‑ ( 3 , 4 ‑ d i h y d r o x y p h e n y l ) ‑
chromeno[4,3,2‑de][1,6]naphthyridine‑4‑carbonitrile (4p,
C21H12N4O4) Yellow solid; m.p.: > 300 °C; Yellow solid;
m.p.: > 300 °C; IR (KBr): v = 3494, 3430, 3385, 3252,
2194 cm1; 1H NMR (300 MHz, DMSO-d6): δ=10.67 (1H,
s), 9.57 (1H, s), 9.28 (1H, s), 8.36–8.38 (1H, d, J=5.7 Hz),
8.03 (1H, s), 7.90–7.91 (1H, d, J=1.8 Hz), 7.75–7.78 (1H,
dd, J=12.3, 4.5 Hz), 7.37 (2H, s), 6.83–6.93 (3H, m) ppm;
13C NMR (75 MHz, DMSO-d6): δ=162.70, 162.24, 162.17,
159.78, 156.01, 153.73, 148.94, 145.94, 138.91, 129.93,
127.03, 120.45, 117.28, 115.98, 115.60, 114.26, 109.48,
103.88, 103.19, 101.63, 76.00 ppm.
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Acknowledgements We gratefully appreciate the University of Sistan
and Baluchestan Research Councils for the fnancial support of this
work.
1 3