γ-Aminobutyric acid hydrochloride supported on superparamagnetic γ-Fe2O3@SiO2 as a novel heterogeneous nanocatalyst for the synthesis of 2-amino-5-alkylidene-thiazol-4-one derivatives

Article abstract of DOI:10.1007/s13738-018-1527-4

γ-Aminobutyric acid hydrochloride immobilized on superparamagnetic γ-Fe₂O₃@SiO₂ nanoparticles as a novel heterogeneous nanocatalyst was prepared for the first times. It was characterized by several techniques such as XRD, FT-IR, VSM, FE-SEM, EDS, and TGA analysis. The heterogeneous nanocatalyst was used for a convenient, mild, and one-pot efficient three-component preparation of 2-amino-5-alkylidene-thiazol-4-one derivatives under green conditions at room temperature. The main advantage of the method is easily recovery of the stable nanocatalyst by an external magnet from the reaction mixture.

Full text of DOI:10.1007/s13738-018-1527-4

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1527-4
ORIGINAL PAPER
γ-Aminobutyric acid hydrochloride supported on superparamagnetic
γ-Fe2O3@SiO2 as a novel heterogeneous nanocatalyst for the synthesis
of 2-amino-5-alkylidene-thiazol-4-one derivatives
Hadi Mohammadi1 · Hamid Reza Shaterian1
Received: 5 May 2018 / Accepted: 11 October 2018
© Iranian Chemical Society 2018
Abstract
γ-Aminobutyric acid hydrochloride immobilized on superparamagnetic γ-Fe2O3@SiO2 nanoparticles as a novel heterogene-
ous nanocatalyst was prepared for the first times. It was characterized by several techniques such as XRD, FT-IR, VSM, FE-
SEM, EDS, and TGA analysis. The heterogeneous nanocatalyst was used for a convenient, mild, and one-pot efficient three-
component preparation of 2-amino-5-alkylidene-thiazol-4-one derivatives under green conditions at room temperature. The
main advantage of the method is easily recovery of the stable nanocatalyst by an external magnet from the reaction mixture.
Keyword Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] · Superparamagnetic nanocatalyst · 2-Amino-5-
alkylidene-thiazol-4-ones · Three-component reaction, · Green reaction
Introduction
the superparamagnetic iron oxide nanoparticles were attract-
ing the consideration of researchers in organic chemistry [8].
Acidic and basic organic compounds have achieved a
great attention in the fields of organic synthesis [9]. In spite
of their widespread use in organic reactions, their practi-
cal applications have been restricted by some difficulties
in its recovery which lead to economical and environmen-
tal problems [10]. The immobilization of acidic and basic
organic compounds onto solid materials can be overcome
by problems accompanied in the use of them [11]. Covalent
anchoring of acidic and basic organic compounds onto a
heterogeneous surface is an attractive approach to its easy
recovery and reuse in chemical processes [12]. Magnetic
nanoparticles (MNPs) have been used as a novel type of
support for organocatalysts as they offer benefits in clean
and sustainable chemistry due to their excellent chemical
stability, good accessibility, reusability, simple preparation
and modification, large surface area, easy separation with an
external magnet, and relatively low toxicity [13, 14]. These
attractive features have made the MNPs a promising alterna-
tive type of catalyst supports.
Organic reactions using heterogeneous catalysts are
extremely important for the development of the concept
of “Sustainable Chemistry” [1]. Nano-sized metal parti-
cles, a new branch of material research, has attracted con-
siderable attention because of their potential applications
in areas such as biotechnology/biomedicine [2], magnetic
resonance imaging (MRI) [3], versatile catalysts for green
and sustainable organic synthesis, magnetic data storage,
and nanocomposites [4]. Nano superparamagnetic transition
metal oxides such as iron are one of the most adjustable sys-
tems which have applied in medical, industrial and biologi-
cal systems in addition to their important roles in catalysis
and organic synthesis [5–7]. Thus, studies of new types of
organometallic compounds grafting of organocatalysts on
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1527-4) contains
supplementary material, which is available to authorized users.
Multi-component reactions (MCRs) have been developed
in preparation of complex organic molecules from simple
and available starting materials without the isolation of any
intermediates. MCRs make efficient pathway in modern
sustainable and “green” synthetic organic compounds [15].
* 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)
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Journal of the Iranian Chemical Society
2-Amino-5-alkylidene-thiazol-4-one derivatives have
been reported in drug discovery, and showed the biologi-
cal, antiviral, antimicrobial, cardiotonic, anti-inflammatory,
inhibitor and anticancer activities (Fig. 1) [16–18].
SiO2 coated by (3-chloropropyl)trimethoxysilane as chloro-
functionalized γ-Fe2O3@SiO2. Finally, the reaction of
γ-aminobutyric acid with chloro-functionalized γ-Fe2O3@
SiO2 formed nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)] as a superparamagnetic nanocatalyst.
In continuation of our research on the supported organo-
catalysts on superparamagnetic materials and their appli-
cations in organic synthesis [19], herein, we have assisted
three-component one-pot synthesis of 2-amino-5-alkylidene-
thiazol-4-one derivatives using a novel heterogeneous nano-
catalyst, nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)], in water–ethanol mixture as a green medium sol-
vent under mild conditions at room temperature (Scheme 1).
The magnetic nanocatalyst was characterized using dif-
ferent techniques such as XRD, SEM, EDS, VSM, TGA and
FT-IR. The XRD pattern of γ-Fe2O3 and nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] had six charac-
teristic peaks which have a good accordance with the cubic
structure of magnetite (γ-Fe2O3) (JCPDS file No. 04-0755).
The positions of all the peaks indicated retention of the crys-
talline structure during functionalization of the MNPs, and
the grafting process did not change phase of the γ-Fe2O3
nanoparticles. The XRD pattern of γ-Fe2O3 and nano-γ-
Fe2O3@[CH2)3-(γ-aminobutyric acid.HCl)] showed that
SiO2 and organocatalyst formed amorphous phase which
their patterns showed only pattern of crystalline γ-Fe2O3
nanoparticles (Fig. 2).
Results and discussion
New nano-γ-Fe2O3@[CH2)3-(γ-aminobutyric acid.HCl)] as
a superparamagnetic nanocatalyst was synthesized based
on the following procedure (Scheme 2). First, superpara-
magnetic Fe3O4 nanoparticles were facilely prepared by a
chemical co-precipitating method. Second, Fe3O4 converted
to γ-Fe2O3 at 300 °C for 3 h and in following γ-Fe2O3 was
coated with tetraethyl orthosilicate (TEOS). Then, γ-Fe2O3@
Figure 3 represents the FE-SEM image of nano-γ-
Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] that
shows spherical morphology and average size 16 nm of
nanoparticles using histogram curve.
O
O
O
O
N
R1
N
N
N
N
S
HO
S
S
O
HO
S
F
HN
O
O
NH2
MeSO3H
N
O
R2
N
H
R3
a
b
c
d
Fig. 1 Structure of some molecules with biological activity: 2-amino-5-alkylidene-thiazol-4-ones (a–c) and isatin–thiazolidinone hybrid (d)
Scheme 1 Synthesis of
2-amino-5-alkylidene-thiazol-
4-one derivatives in the pres-
ence of nano-γ-Fe2O3@SiO2@
[CH2)3-(γ-aminobutyric acid.
HCl)] as a superparamagnetic
nanocatalyst
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Journal of the Iranian Chemical Society
Scheme 2 Synthesis of nano-
γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] as
a new superparamagnetic
nanocatalyst
The VSM diagram shows the magnetic properties of
synthesis catalyst (Fig. 5). The hysteresis loops of organo-
catalysts immobilized on γ-Fe2O3@SiO2 were measured.
Magnetization (emu g−1) as a function of applied field (Oe)
is depicted in Fig. 5 with the confined field from −10,000 to
10,000 Oe. Superparamagnetic behavior of nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] nanocrystals
illustrates small particle size. As it can be observed, satura-
tion magnetization value of nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)] is 60 amu g−1.
The thermal stability of the nano-γ-Fe2O3@SiO2@
[CH2)3-(γ-aminobutyric acid.HCl)] was investigated by
TGA analysis (Fig. 6). Small weight loss occurs below
180 °C, is due to physically adsorbed solvent. There is
exothermic peak accompanied with a mass loss of 6.5% in
the temperature range of 180–480 °C in the TGA curve of
nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)].
These peaks were mainly attributed to the decomposition
of organic groups grafted to the γ-Fe2O3 surface, the peak
higher than 500 °C most probably corresponds to a phase
transition in which the amorphous phase is converted to a
crystalline phase.
Fig. 2 XRD pattern of a γ-Fe2O3, b nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)]
The components of the nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)] were analyzed using EDS. The
EDS spectrum in Fig. 4 implicates the presence of atoms
Fe, O, Si, C, Cl and N in the catalyst which confirm the
structure of the organocatalysts supported on γ-Fe2O3@
SiO2.
The characterization of nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)] was confirmed by FT-IR
spectrum. The C–H stretching vibrations peak appear at
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Journal of the Iranian Chemical Society
Fig. 3 a FE-SEM image of
nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)]; b
particle size distribution histo-
gram curve of nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)]
Fig. 4 EDS spectrum of nano-
γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)]
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Journal of the Iranian Chemical Society
reaction to optimize the reaction conditions such as molar
ratio of the catalyst, temperature and solvents (Table 1,2, 3).
To show the unique catalytic behavior of nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] as nanocatalyst
and to compare its activity with other catalysts, this reac-
tion was performed in the presence of catalytic amount
of Fe3O4 NMPs, p-TSA, AcOH, DBU, sulfamic acid,
MgO–NPs, γ-aminobutyric acid, Et3N, and catalyst free in
different solvents. The results are summarized in Table 1.
With regard to the results in Table 1, It was shown that the
activity of nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)]>Fe3O4 NMPs>FeCl3.6H2O. Excellent yield of
the product (85%) in minimum time period (60 min) was
obtained using MNPs-organocatalyst as catalyst (Table 1,
Entry 6). Also, we examined the reaction in the absence
of any catalyst, and in the presence of nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] as catalyst in
H2O:EtOH(1:1) (3 mL) as solvent (Table 1, Entries 2, 6). It
was found that the best yield of the product was obtained at
room temperature in the presence of 5 mg of MNPs-organo-
catalyst. A similar reaction in the presence of γ-aminobutyric
acid as a non-supported on MNPs gave the desired prod-
uct in moderate yield (55%). The results showed that the
catalytic efficiency of γ-aminobutyric acid was increased
by immobilization onto γ-Fe2O3@SiO2 (Table 1, Entry 6).
Taking into account the data of the Table 1, comparing
the catalyst activity of MNPs-organocatalyst with p-tolu-
ene-sulfonic acid, sulfamic acid, trimethylamine, acetic
acid, magnesium oxide nanoparticles, and 1,8-diazabicy-
clo[5.4.0]undec-7-ene, MNPs-organocatalyst as catalyst
has the advantages of the low ratio of the catalyst in the
Fig. 5 VSM
diagrams
of
nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)]
2930 cm− 1. The Fe–O stretching vibration was observed
550–650 cm−1and stretching mode of C=O showed a peak
at about 1620 cm−1. The O–H stretching bands peak appear
at 3405 cm−1 (Fig. 7).
Optimization of the reaction conditions
To evaluate the activity of the nano-γ-Fe2O3@SiO2@
[CH2)3-(γ-aminobutyric acid.HCl)] as nanocatalyst, at
first, the one-pot and three-component reaction of rodanine
(1 mmol), 4-chlorobenzaldehyde (1 mmol), and 2-amino-
2-thiazoline (1 mmol) (Scheme 3) was chosen as a model
Fig. 6 Thermogravimetric
analysis of nano-γ-Fe2O3@
SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)]
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Journal of the Iranian Chemical Society
Fig. 7 FT-IR spectra: a γ-Fe2O3 and b nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)], c γ-aminobutyric acid
Scheme 3 Synthesis of
5-(4-chloro-benzylidene)-4′,5′-
dihydro-[2,2′]bithiazolyl-4-one
(selected reaction model)
synthesis of 5-(4-chloro-benzylidene)-4′,5′-dihydro-[2, 2′]
bithiazolyl-4-one with good yields, low temperature, and
the reusability of catalyst.
Entries 1, 6, 7, 9), wherein the reaction completed in 60 min
with excellent yield of the product (92%) in H2O:EtOH(2:1)
(Table 2, Entry 10).
In terms of choosing the best solvent for the reaction of
rodanine (1 mmol), 4-chlorobenzaldehyde (1 mmol), and
2-amino-2-thiazoline (1 mmol) (Scheme 3) to afford 4a,
different solvents were studied in the presence of nano-
γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)]
(Table 2). Comparing the reaction times and yields of prod-
ucts in different solvents such as H2O, EtOH, H2O:EtOH
(1:1), H2O:EtOH(1:2), H2O:EtOH(2:1), THF, CH3CN,
CH2Cl2, and solvent-free system, the best result was obtained
after 60 min in H2O:EtOH(2:1) conditions by taking a 1:1:1
molar ratio mixture of rodanine, 4-chlorobenzaldehyde, and
2-amino-2-thiazoline .
The effect of amount of nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] was investigated for the synthesis
of 5-(4-chloro-benzylidene)-4′,5′-dihydro-[2, 2′] bithiazolyl-
4-one. Varying amount of nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)] was used from 2 to 7 mg in
H2O:EtOH(2:1) (3 mL) as solvent (Table 3). The optimum
amount of catalyst for maximum conversion was found to be
5 mg (Table 3, Entry 4). Increasing the amount of nano-γ-
Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] showed
no effect in the product yield (Table 3, Entry 5).
According to optimal considered conditions in this meth-
odology, 2-amino-5-alkylidene-thiazol-4-one derivatives
were synthesized and results are shown in Table 4.
According to the literature [16–18], the proposed
mechanism for the formation of the product is shown
The important of performance of the catalyst in
H2O:EtOH (2:1) relative to the results was obtained in
H2O, EtOH, H2O:EtOH(1:1) and H2O:EtOH(1:2) (Table 2,
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Journal of the Iranian Chemical Society
Table 1 Preparation of 5-(4-chloro-benzylidene)-4′,5′-dihydro-[2, 2′]
bithiazolyl-4-one in the presence of nano-γ-Fe2O3@SiO2@[CH2)3-
(γ-aminobutyric acid.HCl)], Fe3O4 NMPs, p-TSA, AcOH, DBU, sul-
famic acid, Et3N, γ-aminobutyric acid, MgO–NPs, FeCl3.6H2O, and
catalyst-free in different solvents
Entry
Catalyst
Conditions
Time
Yield (%)a,b
Cite to literature
1
2
3
4
5
6
–
–
–
6 h
5 h
2 h
2 h
2 h
60 min
0
–
–
–
–
–
–
H2O:EtOH(1:1) (3 mL) (RT)
H2O:EtOH(1:1) (3 mL) (RT)
H2O:EtOH(1:1) (3 mL) (RT)
H2O:EtOH(1:1) (3 mL) (RT)
Water:EtOH(1:1) (RT)
25
61
55
35
85
p-TSA (30 mol%)
AcOH (30 mol%)
DBU (30 mol%)
Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] (5 mg)
7
8
Et3N (50 mol%)
H2O:EtOH(1:1) (3 mL) (RT)
Solvent free (RT)
100 min
2 h
35
45
–
–
Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] (5 mg)
9
Sulfamic acid (25 mol%)
MgO–NPs (0.3 mol%)
γ-Aminobutyric acid (25 mol%)
FeCl3.6H2O
H2O:EtOH(1:1) (3 mL) (RT)
Water (RT)
H2O:EtOH(1:1) (3 mL) (RT)
H2O:EtOH(1:1) (3 mL) (RT)
H2O:EtOH(1:1) (3 mL) (RT)
90 min
120 min
2 h
2 h
2 h
65
82
55
55
65
–
[16]
-
-
-
10
11
12
13
Fe3O4 NMPs
Table 3 Optimization conditions of the amount of the catalyst for the
preparation of 5-(4-chloro-benzylidene)-4′,5′-dihydro-[2, 2′] bithia-
zolyl-4-one
Table 2 Preparation of 5-(4-chloro-benzylidene)-4′,5′-dihydro-[2, 2′]
bithiazolyl-4-one in the presence of nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] (5 mg) in different solvents
Entry
Catalyst (mg)
Time (min)
Yield (%)a,b
Entry Solvent
Time (min) Tem-
Yield (%)a,b
perature
1
2
3
4
5
2
3
4
5
7
90
85
70
60
50
75
82
87
92
92
(oC)
1
2
3
4
5
6
7
9
EtOH (3 mL)
90
RT
RT
RT
RT
RT
RT
RT
RT
RT
70
45
35
30
45
80
85
75
92
CH3CN (3 mL)
CH2Cl2 (3 mL)
THF (3 mL)
Solvent free
150
150
150
120
70
aReaction conditions: rodanine(1 mmol), 4-chlorobenzaldehyde
(1 mmol), and 2-amino-2-thiazoline(1 mmol) in water:ethanol (2:1)
(3 mL) as a green medium solvent
H2O (3 mL)
bYield refer to isolated pure products
H2O:EtOH(1:1) (3 mL) 60
H2O:EtOH(1:2) (3 mL) 70
H2O:EtOH(2:1) (3 mL) 60
10
aReaction conditions: rodanine(1 mmol), 4-chlorobenzaldehyde
(1 mmol), and 2-amino-2-thiazoline (1 mmol) in different solvent
with nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] as
catalyst
of (E) to produce (F), next, product (4i–v) was obtained
from through displacement of the thiocarbonyl sulfur (F)
with primary or secondary amines (3).
The recyclability of nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] was examined in the one-pot
three-component synthesis of 2-amino-5-alkylidene-thi-
azol-4-one derivatives under optimized conditions. After
completion of reaction, the solvent was separated by fil-
tration, and ethanol was added to the reaction mixture
and heated to separate nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] by an external magnet. The cata-
lyst was washed with ethanol for three times and dried. As
it was shown in Fig. 8, even after five runs, catalytic activ-
ity and product yield have no significant loss. Thus, this
catalyst can endure reaction conditions and remain stable.
bYield refer to isolated pure products
in Scheme 4. At Route 1, first, intermediate (A) was
formed through displacement of the thiocarbonyl sulfur
(2) with primary or secondary amines (3) in the presence
of MNPs-organocatalyst, in the following, intermediate
(B) was obtained, then, the condensation reaction of (B)
with isatins to produce (4a–h). At Route 2, intermediate
(E) was formed through condensation between rhodamine
2 and molecule 1(aldehyde or ketone), and remove water
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Journal of the Iranian Chemical Society
Table 4 Synthesis of 2-amino-5-alkylidene-thiazol-4-one derivatives by nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)] (5 mg) nano-
particles at room temperature in water: ethanol (2:1) (3 mL) as solvent
Entry
amine
product
Time(min)
Yield
(%)a,b
Observed Lit. M.p
M.p (oC) (oC) , Ref
O
H
N
O
N
N
1
60
90
>300
368-370
[16]
O
S
O
O
O
N
O
H
N
H
4a
H
N
O
N
N
2
50
90
>300
345-347
[16]
O
S
N
H
O
N
4b H
H
N
O
N
3
4
N
35
55
89
92
250-253
250-252
[16]
O
S
O
N
H
O
N
H
4c
O
O
H
N
N
N
Cl
>300
350-352
[16]
O
S
O
Cl
N
H
O
O
N
H
4d
N
N
O
O
S
H
N
Cl
5
6
60
92
>300
346-347
[16]
Cl
O
O
N
H
N
H
4e
N
N
H
N
O
S
O
45
89
>300
347-349
[16]
Cl
Cl
O
O
N
H
N
H
4f
H
N
N
N
O
7
60
85
>300
346-348
[16]
O
S
Br
Br
O
O
N
H
N
H
4g
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Journal of the Iranian Chemical Society
Table 4 (continued)
O
N
N
Br
O
S
H
N
8
9
45
85
80
>300
359-361
[16]
O
Br
N
O
H
N
H
4h
H
N
O
120
177-179
178-180
[17]
O
N
N
O
O
O
4i
O
N
N
O
O
H
N
O
10
11
150
70
227-230
228-230
[17]
O
Cl
Cl
4j
O
N
O
H
N
55
95
235-238
236-238
[18]
S
Cl
N
H
O
4k
O
Cl
O
N
O
H
N
S
Me
12
55
95
153-155
152-154
[18]
N
H
Me
4l
O
H
N
H
O
N
13
55
93
163-165
162-164
[18]
S
Br
Br
N
4m
O
N
H
H
O
N
S
14
60
65
90
90
210-213
236-239
210-212
[18]
Br
N
Br
4n
O
H
N
H
O
15
236-238
[18]
N
Cl
S
Cl
N
4o
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Journal of the Iranian Chemical Society
Table 4 (continued)
O
H
N
H
O
15
65
60
65
60
90
93
90
90
236-239
233-236
237-240
180-183
236-238
[18]
N
Cl
S
Cl
N
4o
O
H
H
O
16
17
18
234-236
[18]
N
N
Br
S
Br
N
O
O
4p
O
H2N
O
236-237
[21]
N
S
H
H
HN
4r
S
N
O
New
compound
N
O
NH2
N
S
NH
S
4s
S
N
O
19
60
92
210-213
New
compound
N
O
NH2
N
S
H
NH
S
Cl
Cl
4t
S
N
O
20
55
90
213-215
New
compound
N
O
NH2
N
S
S
H
NH
Br
Br
O
4u
S
N
21
60
95
185-187
New
compound
N
H
O
NH2
N
S
S
NH
Me
Me
4v
aReaction conditions: rodanine(1 mmol), aromatic carbonyl compounds (1mmol) and primary or secondary
amines (1 mmol) in Water:ethanol (2:1) (3ml); bYield refer to isolated pure products.
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Journal of the Iranian Chemical Society
Scheme 4 The proposed
mechanism for the synthesis of
2-amino-5-alkylidene-thiazol-
4-one derivatives in the pres-
ence of nano-γ-Fe2O3@SiO2@
[CH2)3-(γ-aminobutyric acid.
HCl)] as superparamagnetic
nanocatalyst
oarcgidainc o
catalyst
O
MNPs
R'
R
R
N
3
R1
R2
H
1
Route 1
Route 2
R1=H, Alkyl
R2=Aryl
O
M
N
P
R'
s
NH
N
H
N
S
O
H
H
S
oarcgidainc o
catalyst
2
N
S
HO
R1
S
S
S
oarcgidainc o
catalyst
O
(E)
(A)
MNPs
R2
-H2O
-H2S
H
N
O
R'
R
N
S
oarcgidainc o
R1
oarcgidainc o
MNPs
MNPs
S
N
(F)
catalyst
catalyst
S
R2
R'
R
O
(B)
N
H
3
R'
R'
R
R
N
oarcgidainc o
N
MNPs
H
S
catalyst
N
H
N
S
S
HO
(C)
(G)
R2
O
O
R3
R1
O
N
H
4
R'
oarcgidainc o
catalyst
N
N
MNPs
R
R'
O
-H2S
R
S
N
R3
OH
O
N
R'
S
N
-H2O
N
R
H
N
(D)
O
4i-v
R2
O
S
R1
R3
4a-h
O
N
H
HO
oarcgidainc o
catalyst
H2
N
MNPs
γ
-Fe2O3@ SiO2@[CH2)3-(γ-aminobutyric acid.HCl)]
=
=
O
Cl
characterization of MNPs-organocatalyst as a catalyst was
performed according to FT-IR spectra which recorded using
KBr disks on a JASCO FT-IR 460 plus spectrophotometer
and 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 diffrac-
tion (XRD) was performed on a Bruker D8-advance X-ray
diffractometer with Cu Kα (λ = 0.154 nm) radiation. The
magnetic property of γ-Fe2O3 supported was measured with
(VSM/AGFM). TGA was done on a thermal analyzer with
Experimental
Materials and Methods
All materials were purchased from Merck and Aldrich Com-
pany. The NMR spectra were provided on Brucker Avance
300 MHz instruments in DMSO-d6. Melting points were
determined in open capillaries using a BUCHI510 melting
point apparatus. The progress of the reactions was moni-
tored by TLC. Thin-layer chromatography (TLC) was per-
formed on silica-gel Poly Gram SIL G/UV 254 plates. The
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Journal of the Iranian Chemical Society
Fig. 8 Reusability of nano-
γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)]
a heating rate of 10 °C min−1 over a temperature range of
25–800 °C under flowing compressed N2.
and ammonia solution(3 mL) were added to the dispersed
ethanolic solution of γ-Fe2O3@SiO2 and stirred for 24 h at
room temperature. The silica-coated nanoparticles by an
external magnet were collected, followed by washing three
times with ethanol and drying at 70 °C for 12 h.
Preparation of nano‑γ‑Fe2O3@SiO2@
[CH2)3‑(γ‑aminobutyric acid.HCl)]
as a superparamagnetic heterogeneous
nanocatalyst
Preparation of nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric
acid. HCl)] as a superparamagnetic nanoparticles
Preparation of γ-Fe2O3
The chloro-functionalized γ-Fe2O3@SiO2 (1 g) was dis-
persed in 30 mL distilled water and γ-aminobutyric acid
(1 g) dissolved in 50 mL ethanol–water (1:1) was added
to the dispersed MNPs and the reaction mixture stirred at
room temperature for 24 h. The MNPs-organocatalyst was
then isolated by simple magnetic decantation, sequentially
washed with water and ethanol three times, and finally dried
at 60 °C for 12 h. The successful synthesis of MNPs-organo-
catalyst was confirmed by the FT–IR, EDX, SEM, TGA,
VSM, and XRD analyses.
The Fe3O4 nanoparticles were prepared according to a pre-
viously reported procedure [20]. FeCl2.4H2O (1.25 g) and
FeCl3.6H2O (3.33 g) were dissolved in water (80 mL) sepa-
rately, followed by the two iron salt solutions being mixed
under continuously stirring (800 rpm). Then, a NH4OH solu-
tion (%25, 60 mL) was drop added to the stirring mixture
at room temperature for 3 h and stirring continued for 1 h;
the black products were collected by an external magnet.
Then, Fe3O4 MNPs were washed three times with water and
ethanol, and dried at 60 °C for 12 h. Fe3O4 nanoparticles at
this stage are heated at 300 °C in a furnace for 3 h to convert
Fe3O4 to sustainable γ-Fe2O3 nanoparticles.
General procedure for the direct synthesis
of 2-amino-5-alkylidene-thiazol-4-one derivatives (4a–h)
using nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.
HCl)] catalyst.
Preparation of γ-Fe2O3 @SiO2
γ-Fe2O3 nanoparticles (1 g) were dispersed in ethanol
(40 mL) and the resulting mixture was stirred for 1 h at
40 °C. Subsequently, tetraethyl orthosilicate (TEOS, 2 mL)
was charged to the reaction vessel, and the mixture was con-
tinuously stirred for 24 h. The silica-coated nanoparticles
were collected by an external magnet, followed by washing
three times with ethanol and drying at 70 °C for 12 h causing
the formation of γ-Fe2O3 @SiO2.
Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)]
(5 mg) was added to a mixture rodanine (1 mmol), primary
or secondary amines (1 mmol) and stirred at room tem-
perature in water:ethanol (2:1) (3 ml) for some minutes;
then, isatins (1 mmol) were added to a mixture reaction.
After completion of reaction, the solvent was separated by
filtration, and ethanol was added to the reaction mixture
and heated to separate nano-γ-Fe2O3@SiO2@[CH2)3-(γ-
aminobutyric acid.HCl)] by external magnet. The catalyst
was washed with ethanol for three times and dried. The
warm ethanolic solution containing crude product was
cooled until precipitated pure product was formed. The
known pure products were characterized and compared
Preparation of chloro-functionalized γ-Fe2O3@SiO2
γ-Fe2O3@SiO2 nanoparticles (1 g) were dispersed in ethanol
(40 mL). After that (3-chloropropyl)triethoxysilane (0.5 mL)
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Journal of the Iranian Chemical Society
their physical data with those of known compounds. The
characterization of new unknown products was represented
as below.
5-(4-Bromo-benzylidene)-4′,5′-dihydro-[2 2′]
bithiazolyl-4-one (4u)
Yellow solid; mp: 213–215 °C. IR (KBr) (νmax /cm− 1):
3291, 2044, 2847,1668, 1272. 1H NMR (300 MHz, DMSO-
d6): δH (ppm) 3.54–3.59 (2H, t, J=7.52 Hz, CH2), 3.87–3.92
(2H, t, J=7.52 Hz, CH2), 7.39 (1H, s, =CH),7.47–7.71 (4H,
m, H-Ar), 9.52(1H,w,NH). 13C NMR (75 MHz, DMSO-d6):
δC (ppm) 31.56, 49.18, 123.52, 126.87, 131.77, 132.26,
132.64, 133.73 ,173.24, 176.82, 199.53.
General procedure for the direct synthesis
of 2-amino-5-alkylidene-thiazol-4-one derivatives (4i–v)
using nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.
HCl)] as catalyst.
Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)]
(5 mg) was added to a mixture rodanine(1 mmol), aromatic
carbonyl compounds(aldehydes or ketones) (1 mmol) and
stirred at room temperature in water:ethanol(2:1) (3 ml)
for some minutes, then primary or secondary amines
(1 mmol) added to a mixture reaction. After the comple-
tion of reaction, the solvent was separated by filtration,
ethanol was added to the reaction mixture and heated to
separate nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric
acid.HCl)] by external magnet. The catalyst was washed
with ethanol for three times and dried. The warm ethanolic
solution containing crude product was cooled until precip-
itated pure product was formed. The known pure products
were characterized and compare their physical data with
those of known compounds. The characterization of new
unknown products is represented as below.
5-(3-Methyl-benzylidene)-4′, 5′-dihydro-[2, 2′]
bithiazolyl-4-one (4v)
Yellow solid; mp:185–187 °C. IR (KBr) (νmax /cm− 1):
3281, 3074, 2850, 1694, 1291. 1H NMR (300 MHz, DMSO-
d6): δH (ppm) 2.37(3H,s, CH3) 3.53–3.58 (2H, t, J=7.52 Hz,
CH2), 3.86–3.91 (2H, t, J=7.52 Hz, CH2), 7.28–7.45 (4H,
m, H-Ar),7.50 (1H, s, =CH),9.33(1H,w,NH). 13C NMR
(75 MHz, DMSO-d6): δC (ppm) 21.40, 31.52, 49.17,
127.82, 127.97, 129.71, 130.58, 131.20, 131.51, 133.85,
139.15,172.73, 173.23, 197.70.
Conclusion
Nano-γ-Fe2O3@SiO2@[CH2)3-(γ-aminobutyric acid.HCl)]
as a novel organometallic heterogeneous nano-magnetic cat-
alyst has been successfully synthesized and characterized by
the several techniques such as XRD, FT-IR, VSM, FE-SEM,
EDS, and TGA-DTG analysis. This efficient nano-organo-
metallic catalyst was successfully used for the three-com-
ponent preparation of 2-amino-5-alkylidene-thiazol-4-one
derivatives under green conditions. 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 superpara-
magnetic nanocatalyst is magnetically separable and stable
in the reaction conditions without detectable activity loss.
Experimental characterization data and spectra
of the new compounds.
5-(Benzylidene)-4′,5′-dihydro-[2, 2′] bithiazolyl-4-one (4s)
Yellow solid; mp:180–183 °C. IR (KBr) (νmax /cm− 1):
1
3272, 3041, 2851, 1669, 1285. H NMR (300 MHz,
DMSO-d6): δH (ppm) 3.54–3.59 (2H, t, J = 7.52 Hz,
CH2), 3.87–3.92 (2H, t, J = 7.52 Hz, CH2), 7.40 (1H, s,
=CH),7.43–7.58 (4H, m, H-Ar), 9.94(1H,w,NH). 13C
NMR (75 MHz, DMSO-d6): δC (ppm) 31.60, 49.22,
127.93, 129.66, 130.01, 130.48, 131.36, 134.58 ,173.24,
177.72, 200.43.
Acknowledgements We are grateful for financial support from the
Research Council of University of Sistan and Baluchestan.
5-(4-Chloro-benzylidene)-4′,5′-dihydro-[2, 2′]
bithiazolyl-4-one (4t)
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