EtOAc-dispersed magnetic nanoparticles (DMNPs) of γ-Fe 2O3 in the single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives

Article abstract of DOI:10.1016/j.crci.2013.03.002

EtOAc-dispersed magnetic nanoparticles (DMNPs) of γ-Fe ₂O₃ represent a straightforward and green catalyst for the rapid three-component synthesis of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives as rhodanine skeletons via a single-pot domino process. The rhodanines were prepared over magnetic nanoparticles of γ-Fe ₂O₃ without any salt or additives. Dispersed nano-γ-Fe₂O₃ have many advantages, such as stability in air, reusability, reactions with high efficiency, simple separation with magnetic external field from mixture reactions, chemical stability, and also low toxicity.

Full text of DOI:10.1016/j.crci.2013.03.002

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CRAS2C-3727; No. of Pages 5
C. R. Chimie xxx (2013) xxx–xxx
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Full paper/M e´ moire
EtOAc-dispersed magnetic nanoparticles (DMNPs) of
single-pot domino preparation of 5-oxo-2-thioxo-3-
thiophenecarboxylate derivatives
g-Fe O in the
2 3
Sadegh Rostamnia
Organic and Nano Group (ONG), Department of Chemistry, Faculty of Science, University of Maragheh, PO Box 55181-83111, Maragheh, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
2 3
EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O represent a straightforward
Received 31 December 2012
Accepted after revision 1 March 2013
Available online xxx
and green catalyst for the rapid three-component synthesis of 5-oxo-2-thioxo-3-
thiophenecarboxylate derivatives as rhodanine skeletons via a single-pot domino process.
The rhodanines were prepared over magnetic nanoparticles of
2 3
g-Fe O without any salt or
additives. Dispersed nano- -Fe have many advantages, such as stability in air,
g
2 3
O
Keywords:
reusability, reactions with high efficiency, simple separation with magnetic external field
from mixture reactions, chemical stability, and also low toxicity.
ß 2013 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Multicomponent reaction
Rhodanine
2 3
Nano-g-Fe O
Dispersed magnetic nanoparticles (DMNPs)
1
. Introduction
Rhodanine heterocyclic skeletons are known to possess
considered as following the principles of green chemistry,
i.e. they consume a minimum of energy and reagents or
auxiliaries, and minimize wastes [4]. Magnetic separation
of MNPs is simple, economical and promising for industrial
applications. From both economic and environmental
viewpoints, organic reactions in aqueous medium using
recoverable catalysts have gained attention in recent years
[5].
For the above reasons, we were, thus, intrigued by the
possibility of applying nano- and green chemistry to the
design of an active, recyclable, and magnetically recover-
multiple biological activities, including the inhibition of
numerous targets, such as PMT1 manosyl transferase [1],
PRL-3 and JSP-1 phosphatases [2]. Classical methods for
the preparation of alkylidine rhodanine need several steps
and generally involve the preparation of the rhodanine
moiety followed by a Knoevenagel condensation with
aldehydes [3]. Recent methods are limited by the require-
ment of highly reactive functional groups in the substrates
and by the fact that they do not proceed in smooth and
mild conditions. Several methods have been reported for
the synthesis of rhodanines [3]. However, they all rely on
multistep reactions with either hard conditions or low
yields, and the reaction times are long. Thus, the
development of new synthetic methods remains an
attractive goal.
2 3
able dispersed nano-g-Fe O catalyst in EtOAc-medium for
the synthesis of alkyl rhodanines under mild reaction
conditions.
2. Results and discussion
Recently, we have developed synthetic methods for the
synthesis of biologically interesting heterocycles via
multicomponent reactions [6]. The challenge in this field
was to develop efficient and rapid green methods. More-
over, the synthesis of these heterocycles has usually been
carried out in polar solvents, such as DMF and DMSO,
Organic processes catalyzed by non-toxic magnetic
3 4 2 3
nanoparticles (MNPs), such as Fe O and Fe O , are often
E-mail addresses: srostamnia@gmail.com, rostamnia@maragheh.ac.ir.
1
631-0748/$ – see front matter ß 2013 Acad e´ mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.03.002
2 3
Please cite this article in press as: Rostamnia, S., EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O in the
single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives. C. R. Chimie (2013), http://
dx.doi.org/10.1016/j.crci.2013.03.002

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S. Rostamnia / C. R. Chimie xxx (2013) xxx–xxx
Fig. 1. Transmission electron microscopy (TEM) image of the g-Fe2O3 nanoparticles.
leading to complex isolation and recovery procedures.
Also, based on our recent success in the preparation of
MNPs as catalysts [6], combined with our achievments in
this area, we present, in this paper, the results of an
Initial studies of the influence of the reaction conditions
were carried out with the model reaction. By screening a
wide range of iron sources, mol% of catalyst and different
solvents and temperatures, we found that the product 3a
could be obtained in yields ranging from 17 to 95% (entry
1–12, Table 1). When we have changed the amount of the
catalysts from 5 mol% to 15 mol%, finding out that 10 mol%
was enough for the best yield.
2 3
extended investigation on the activity of dispersed g-Fe O
in EtOAc-medium as a green magnetic separable nanoca-
talyst in a domino three-component process leading to the
formation of alkyl rhodanines without any salts or
additives. We have developed a synthetic method for
the preparation of 5-oxo-2-thioxo-3-thiophenecarboxy-
late via the condensation of an aliphatic amine, carbon
disulfide and the electron-deficient acetylene using a
With these results in hand and to demonstrate the
2 3
diversity of the dispersed MNPs (DMNPs) of g-Fe O as a
nanocatalyst and to expand the scope of the process, the
optimized conditions were applied to a series of substrates
1 and 2, as shown in Table 2.
dispersed tecnique of small size (ꢀ30 nm range, Fig. 1) of
g-
Fe as the active catalyst. Herein, the condensation of
2
O
3
2 3
The catalytic activity of g-Fe O in the domino three-
benzyl amine, carbon disulfide and dimethyl acetylenedi-
carboxylate (DMAD) was selected to be the model (Table
component process for synthesizing rhodanine 3a and 4
was also studied under optimized conditions. When we set
the reaction with a mixture of an aromatic amine (aniline)
and an aliphatic amine (benzyl amine) in the presence of
2 3
1). Also, the MNP to form g-Fe O was synthesized by basic
precipitation from the iron source [8].
Table 1
a
Optimization of reaction conditions for the synthesis of rhodanine 3a .
E
S
NH2
H
3
CO
γ -Fe O
2 3
+
CS
2
+
N
S
3
a
Conditions
O
E = CO Me
2
O
E
Entry
Fe-source
Solvent
Cat.
T
Time
Yield
(%)
(mol%)
(8C)
(min)
1
2
3
4
5
6
7
8
9
FeCl
FeSO
-Fe
Bulk-Fe
Nano-Fe
3
ꢁ6H
2
O
THF
5
5
5
5
5
4
5
5
5
40
r.t.
50
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
5
5
24
17
26
20
31
37
43
61
75
73
95
94
4
CCl
CCl
CCl
CCl
CCl
4
b
g
2
O
3
/SiO
2
ꢁMNPs
4
4
4
4
5
3
O
4
5
3
O
4
5
g
g
g
g
g
g
g
-Fe
-Fe
-Fe
-Fe
-Fe
2
2
2
2
2
O
O
O
O
O
3
3
3
3
3
ꢁMNPs
ꢁMNPs
5
H
2
O
5
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
5
10
5
1
1
1
0
1
2
10
10
15
-Fe
-Fe
2
O
3
10
10
2 3
O
r.t: room temperature. Bold: final selected row as optimized condition.
a
Reaction scale: 3 mmol.
b
Synthesized based on our previous report [6i].
2 3
Please cite this article in press as: Rostamnia, S., EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O in the
single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives. C. R. Chimie (2013), http://
dx.doi.org/10.1016/j.crci.2013.03.002

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3
Table 2
a
3
The synthesis of the 5-oxo-2-thioxo-3-thiophenecarboxylate skeleton by
g-Fe
2
O
.
R'
S
CO R'' γ -Fe O3
NH2
R'
2
2
1
0 mol%
R''O
+
CS
2
+
R
N
S
R
EtOAc, r.t.
O
1
2
O
3
CO R''
2
0
0
0
R
3
R
R
Yield% 3
Mp (8C)
Reported
Found
3
3
3
3
3
3
3
3
a
C
C
6
H
5
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
CH
3
H
95
95
93
90
90
90
95
85
128–130 [6e]
89–91 [6e]
112–114 [6e]
104–106 [6e]
–
131–133
87–90
b
c
6
H
5
CH
H
3
o-Cl–C
o-Cl–C
p-Cl–C
6
6
6
H
4
4
113–115
105–109
114–117
85–90
d
e
f
H
CH
2
H
H
4
H
i
Pr
H
88–90
g
h
CH
Vinyl
3
CH
H
3
–
60–66
140–142 [6e]
139–144
a
Reaction scale: 3 mmol.
NH2
NH2
S
S
S
CS /DMAD
2
γ-Fe O (10 mol%)
2
3
Ph
S
N
N
Ph
+
+
EtOAc, r.t. 3h
E
O
E
O
(5 mmol)
(5 mmol)
E = CO Me
(3a, 89%)
(4, 0%)
2
Scheme 1. Chemoselective synthesis of alkyl rhodanines.
carbon disulfide and dimethyl acetylenedicarboxylate
DMAD), the yield of 3a was 89% after 15 min, without
any detected product 4 (Scheme 1).
Although we have not established the exact mechanism
for our method in an experimental manner, the following
rationalization may be advanced to explain the product
(
The possibility of recycling the dispersed magnetic
catalyst was also studied. When the reaction was
completed, the catalyst was easily separated from the
product by attaching an external magnet onto the reaction
vessel. As illustrated in Table 3, the catalyst could be still
reused after the sixth run.
3 4
formation [6e,7]. Presumably, the g-Fe O stabilized
zwitterion 5 from amine and carbon disulfide was attached
by active acetylene to furnish a cumulene 6 or dithio-
carbamate 7 intermediate. The final product 3a is produced
by
3 4
g-Fe O accelerated methanol elimination and cycliza-
tion of 6 or 7 (Scheme 2).
Table 3
Recyclability study on the synthesis of model compound 3a.
a
Run
1
2
3
4
5
6
Yield% 3a
95
93
91
87
88
73
a
Time of the reaction was 2 h.
2 3
Please cite this article in press as: Rostamnia, S., EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O in the
single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives. C. R. Chimie (2013), http://
dx.doi.org/10.1016/j.crci.2013.03.002

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S. Rostamnia / C. R. Chimie xxx (2013) xxx–xxx
Scheme 2. Plausible mechanism for the magnetic nanoparticles-catalyzed synthesis of rhodanine.
3
. Conclusion
4.2. General procedure for the preparation of compound 3a–
h: preparation of 3a
In summary, an extensive and systematic study allowed
us to identify MNPs of
g
-Fe
2
O
3
as a heterogeneous, green
Benzyl amine (3 mmol) and carbon disulfide (3.3 mmol)
were added to a dispersion of MNPs (10 mol%) in ethyl
acetate (3 mL), and the mixture was stirred at room
temperature for 30 s; then 3 mmol of DMAD were added to
the mixture during 30 s. The reaction progress was
monitored by TLC. Finally, the catalyst was extracted
under a magnetic external field, and reaction products
were diluted in water, then the organic phase was
extracted and the pure product was recrystallized. All
isolated products gave satisfactory spectral and physical
data. All the products were previously reported [6e] and
were characterized by comparison with IR and physical
data. Spectral data for the selected product: Ethyl 2-[3-((4-
and reusable catalyst for the synthesis of rhodanines via a
domino process. This rapid, green method, in which the
catalyst can be recycled, should be an interesting alter-
native to other synthesis methods. The method has several
advantages, including high yields of products, recyclability
of the catalyst, non-toxicity, easy experimental work-up
procedure, and the fact that the catalyst is environmentally
friendly.
4
. Experimental
All the reagents were obtained from Merck (Germany)
and Fluka (Switzerland) and were used without further
purification. IR spectra were recorded on a Shimadzu IR-
60 spectrometer. The melting points were measured on
an Electrothermal 9100 apparatus. The progress of
reactions was monitored by thin layer chromatography
chlorophenyl)methyl)-4-oxo-2-thioxo-1,3-thiazolan-5-ylide-
ꢂ1
n]ethanoate (3e) Orange powder. IR (KBr) (
n
max, cm ):
1
1728 (CO), 1649 (CC), 1310 and 1177 (CS). H NMR
(500 MHz, CDCl ): = 3.87 (3 H, s, OCH ), 5.24 (2 H, s,
CH Ph), 6.84 (1 H, s, C5CH), 7.28 (2 H, d, JHH = 8.4 Hz, 2 CH
of Ar), 7.37 (2 H, d, JHH = 8.4 Hz, 2 CH of Ar) ppm. C NMR
(125.7 MHz, CDCl ): = 46.62 (OCH ), 52.89 (CH Ph),
17.16 (C5CH), 128. 86 (2 CH of Ar), 130.49 (2 CH of Ar),
132.79 (Cipso of Cl), 134.36 (Cipso of NC), 141.82 (C5CH),
65.45 (CON), 166.46 (CO CH ), 195.43 (C5S) [6e,7].
4
3
d
H
3
3
2
3
13
(
TLC).
.1. Synthesis magnetic nanoparticles of
Maghemite -Fe nanoparticles were synthesized
3
d
C
3
2
1
4
2 3
g-Fe O (MNPs)
1
2
3
g
2 3
O
based on an interesting method reported by Kolvari,
Khazaei and Zolfigol [8], with minor modifications. After
adding a Fe-source and a reductive reagent, and after the
color of the solution turned back from red to light yellow,
the solution was added to an ammonia solution under
stirring; to achieve uniform particle size and stability of
MNPs, oleic acid was added.
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Please cite this article in press as: Rostamnia, S., EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O in the
single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives. C. R. Chimie (2013), http://
dx.doi.org/10.1016/j.crci.2013.03.002

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Please cite this article in press as: Rostamnia, S., EtOAc-dispersed magnetic nanoparticles (DMNPs) of g-Fe O in the
single-pot domino preparation of 5-oxo-2-thioxo-3-thiophenecarboxylate derivatives. C. R. Chimie (2013), http://
dx.doi.org/10.1016/j.crci.2013.03.002