Magnetic carbon nanotube-supported imidazolium cation-based ionic liquid as a highly stable nanocatalyst for the synthesis of 2-aminothiazoles

Article abstract of DOI:10.1002/aoc.3540

Magnetic carbon nanotube-supported imidazolium ionic liquid (CNT-Fe₃O₄-IL) was synthesized and investigated using various characterization techniques, including Fourier transform infrared and Raman spectroscopies, X-ray diffraction, vibrating sample magnetometry, scanning and transmission electron microscopies, and thermogravimetric and differential thermal analyses. In order to synthesize the CNT-Fe₃O₄-IL nanocomposites, Fe₃O₄-decorated multi-walled CNTs were modified with 1-methyl-3-(3-trimethoxysilylpropyl)-1H-imidazol-3-ium chloride. This catalytic system was found to be a highly stable, active, reusable and solid-phase catalyst for the synthesis of 2-aminothiazoles via the one-pot reaction of ketone, thiourea and N-bromosuccinimide under mild conditions. Immobilized magnetic ionic liquid catalysis combines the advantages of ionic liquid media with magnetic solid support nanomaterials which enables the application of nanotechnology and green chemistry in chemical processes. Copyright

Full text of DOI:10.1002/aoc.3540

Full paper
Received: 30 April 2016
Revised: 20 May 2016
Accepted: 22 May 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3540
Magnetic carbon nanotube-supported
imidazolium cation-based ionic liquid as a
highly stable nanocatalyst for the synthesis
of 2-aminothiazoles
Zohre Zarnegar and Javad Safari*
3 4
Magnetic carbon nanotube-supported imidazolium ionic liquid (CNT-Fe O -IL) was synthesized and investigated using various
characterization techniques, including Fourier transform infrared and Raman spectroscopies, X-ray diffraction, vibrating sample
magnetometry, scanning and transmission electron microscopies, and thermogravimetric and differential thermal analyses. In or-
3 4 3 4
der to synthesize the CNT-Fe O -IL nanocomposites, Fe O -decorated multi-walled CNTs were modified with 1-methyl-
3-(3-trimethoxysilylpropyl)-1H-imidazol-3-ium chloride. This catalytic system was found to be a highly stable, active, reusable
and solid-phase catalyst for the synthesis of 2-aminothiazoles via the one-pot reaction of ketone, thiourea and
N-bromosuccinimide under mild conditions. Immobilized magnetic ionic liquid catalysis combines the advantages of ionic liquid
media with magnetic solid support nanomaterials which enables the application of nanotechnology and green chemistry in
chemical processes. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: ionic liquid; Fe O nanoparticles; 2-aminothiazoles; carbon nanotubes; N-bromosuccinimide
3
4
With the recent progress in the area of magnetic nanostructures,
magnetically immobilized ionic liquids have received much atten-
tion in a wide range of different areas including biological
Introduction
2-Aminothiazoles are one of the most important classes of heterocy-
[
21]
[22]
[23]
cles that contain nitrogen and sulfur and are present in compounds
possessing various pharmaceutical properties such as anticancer and
systems,
biosensors,
purification of polluted water,
cata-
[
24]
[25]
[26]
lytic processes, magnetic membranes, polymer synthesis,
[1]
[2]
[3]
[4]
[27]
[28]
antitumor, anticonvulsant, antidiabetic, antihypertensive,
thermoset materials and extraction of protein. In fact, ionic
liquids, with extended advantages such as low vapour pressure,
non-corrosiveness, wide liquid range, non-volatility, thermal and
chemical stability, good conductivity and modifiable chemical
structures, offer a basis for modern chemistry and improved
[
5]
[6]
[7]
anti-inflammatory, antiviral, antileishmanial and antimicrobial
[8]
activities. They are the core structural skeletons in many important
natural compounds such as vitamin B1 (thiamine), penicillin and
[9]
carboxylase.
[
24]
Apart from conventional approaches, several methods have been
developed for the synthesis of 2-aminothiazoles. The most general
methodology involves condensation of α-haloketones with thiourea
in the presence of a condensing agent such as bromine/iodine or
using various catalysts such as iodine,
technologies. However, there are some disadvantages of homo-
geneous ionic liquids such as tedious recovery procedure via filtra-
tion or centrifugation, high viscosity and the use of a large amount
of ionic liquid in many situations. In this regard, heterogeneous
immobilized ionic liquids, combining ionic liquids with heteroge-
neous support nanomaterials, have attracted considerable interest
due to the advantages such as easy separation, effective reusability,
[
10]
[
11]
[12]
KI/NH
4
NO
3
,
1,3-
[
13]
[14]
di-n-butylimidazolium
tetrafluoroborate,
β-cyclodextrin,
[
15]
[16]
[
bmim]BF
4
,
ammonium 1,2-molybdophosphate,
silica
Recently, Keshari and Kapoorr reported
the synthesis of 2-aminothiazoles by oxidative cyclocondensation
of ketones and thiourea using CBr as a convenient and mild bromi-
nating reagent under basic conditions at room temperature.
Furthermore, we have also developed a synthetic protocol for
-aminothiazoles via condensation of ketones with thiourea using
[
17]
[18]
[29]
chloride and NaICl
2
.
low cost and operational simplicity.
In recent years, carbon nanostructures such as carbon nanotubes
(CNTs) as excellent heterogeneous supports have attracted much
attention due to their intriguing nanoscale dimensions, high electri-
cal conductivity, high specific surface area, high mechanical
strength, uniform nanostructure and thermal and chemical
4
[
19]
2
[
20]
I2 as an iodination agent and nanochitosan as a catalyst.
It is
important to note that magnetic nanocatalysts are not stable in
the presence of I as reagent for iodination. Magnetic nanocatalysts
2
*
Correspondence to: Javad Safari, Laboratory of Organic Compound Research,
Department of Organic Chemistry, College of Chemistry and Biochemistry,
University of Kashan, PO Box 87317-51167, Kashan, IR Iran. E-mail:
safari_jav@yahoo.com; safari@kashanu.ac.ir
are decomposed and not recyclable in acidic conditions (HI
produced during the reaction). To overcome this problem and for
the development of stable magnetic nanocatalytic systems, we thus
decided to design
a new method for the synthesis of
Laboratory of Organic Compound Research, Department of Organic Chemistry,
College of Chemistry and Biochemistry, University of Kashan, PO Box 87317-
51167, Kashan, IR, Iran
2-aminothiazoles. In this context, magnetically supported ionic
liquids are stable and active catalysts.
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

Z. Zarnegar and J. Safari
[30,31]
stability.
Also, magnetic nanostructures such as Fe
O
3 4
nano-
3 4
Preparation of CNT-Fe O -IL Nanocomposites
particles are ideal supports because of their high activity, low cost,
availability, high surface area, non-toxicity and easy modification
Methylimidazolium chloride was synthesized by the reaction of
[
32,33]
(3-chloropropyl)trimethoxysilane with N-methylimidazole at 80 °C
with other organic or inorganic species.
So, the design and
[
33]
under solvent-free conditions. In order to prepare the supported
ionic liquid, 0.60 g of CNT-Fe was dispersed in 20.0 ml of anhy-
drous toluene under ultrasound irradiation. Next, 20 mmol (5.60 g)
of imidazolium ionic liquid and 0.60 ml of 28% NH OH were added
preparation of novel and efficient series of ionic liquids immobilized
on magnetic CNTs can afford an opportunity to achieve new
heterogeneous ionic liquid-based nanomaterials with high perfor-
mance in engineering applications due to the extended advan-
tages such as easy separation using a simple external magnetic
field, effective recovery and reusability, low cost and operational
simplicity.
3 4
O
4
dropwise and stirred for another 36 h at room temperature. The
magnetic nanohybrids were magnetically recovered and washed
thoroughly several times with ethanol and double-distilled water.
3 4
The purified magnetic CNT-Fe O -IL was dried at 70 °C.
The availability and broad usefulness of ionic liquids in
catalytic processes prompted us to develop new, highly stable
and active immobilized ionic liquid-based magnetically recov-
erable CNTs as nanocatalysts. As a follow-up to research on
recoverable ionic liquids immobilized on magnetic supports
General procedure for preparation of 2-Aminothiazole
A mixture of methylcarbonyl (2 mmol), thiourea (2 mmol), I or NBS
2
(
2.5 mmol), and CNT-Fe
at reflux conditions, the reaction progress being monitored by TLC
eluting with petroleum ether–ethyl acetate, 4:1). After completion
3 4
O -IL (0.025 g) in ethanol (5 ml) was stirred
[
24]
for various organic reactions,
herein we report the prepara-
tion and characterization of an imidazolium ionic liquid
immobilized on CNT-supported Fe O4 (CNT-Fe O -IL). This
(
3
3 4
of the reaction, the magnetic organocatalyst was separated using
an external magnetic field. After evaporation of EtOH under
reduced pressure, the residue was dissolved in boiling water,
extracted with ether (3 × 30 ml) and the pH adjusted to 8 with
ammonia to give solid product. The solid was purified by recrystal-
lization from ethanol–water to afford pure product.
magnetic nanocatalyst allows efficient condensation of
ketones and thiourea in the presence of N-bromosuccinimide
(
NBS) for the synthesis of 2-aminothiazoles with high yield of
product (Scheme 1). This is the first report wherein the
benefits of ionic liquids are combined with the superb
properties of CNTs and magnetic nanoparticles for organic
reactions.
Results and discussion
In our previous study, we developed a synthetic method for the
preparation of 2-aminothiazoles from condensation of ketones
Experimental
[
20]
and thiourea using I /nanochitosan. At first, we considered the
Chemicals and apparatus
2
possibility of catalysing the reaction of ketones in situ to obtain
α-iodoketones, which can react with thiourea in one-pot condensa-
Most of the reagents used were purchased from Merck, Aldrich and
2
À1
Sigma. Multi-walled CNTs with surface area of 136 m g and
0–20 nm in diameter were supplied by Neutrino Company, Iran.
tion to afford 2-aminothiazole in the presence of I and different
2
1
types of magnetic nanocatalysts. The challenge in this synthetic
method was the development of a stable magnetic catalytic system
during chemical process, because magnetic catalysts were
decomposed. Therefore, in the present research, we used NBS
Melting points were determined with an Electrothermal MK3
apparatus using an open-glass capillary and are uncorrected.
Fourier transform infrared (FT-IR) spectra were recorded with a
À1
PerkinElmer 550 instrument in the range 400–4000 cm . NMR
3 4
and CNT-Fe O -IL as a stable and highly active magnetic catalytic
spectra were recorded with a Bruker DRX-400 spectrometer.
Elemental analysis (C, H, N) was conducted with a Carlo Erba model
EA 1108 analyser and a PerkinElmer 240c analyser. Magnetic
nanohybrids were characterized using XRD with a Philips Xpert
X-ray diffractometer (Cu Kα radiation, λ = 0.154056 nm), at a
system for in situ synthesis of α-haloketones from ketones which
then react with thiourea.
Characterization of catalyst
À1
scanning speed of 2° min from 10° to 100° (2θ). The surface
The preparation route for CNT-Fe O -IL magnetic nanocomposites is
3
4
morphology of samples was characterized using scanning electron
microscopy (SEM; EM3200) and transmission electron microscopy
shown in Scheme 2. The imidazolium ionic liquid was prepared by the
reaction of N-methylimidazole with (3-chloropropyl)trimethoxysilane.
Then, Fe O nanoparticles were immobilized on the surface of CNTs
(TEM; Philips CM10). Thermogravimetric analysis (TGA) profiles
3
4
were obtained using a PL-STA 1500 thermal analyser at a uniform
heating rate of 15 °C min under nitrogen flow. The magnetic
in order to prepare CNT-Fe O . The reaction of imidazolium ionic
3 4
liquid with CNT-Fe O afforded the supported ionic liquid. These pro-
3 4
À1
measurements of samples were conducted using vibrating sample
magnetometry (VSM; 4 inch, Daghigh Meghnatis Kashan Co.,
Kashan, Iran) at room temperature.
cesses were monitored using FT-IR and Raman spectroscopies, XRD,
SEM, TEM, energy-dispersive X-ray analysis (EDX), TGA, differential
thermal analysis (DTA) and VSM.
Figure 1 shows the FT-IR spectrum of CNT-Fe O -IL in the range
3
4
À1
À1
4
00–4000 cm . The broad band at 3443 cm corresponds to
the presence of surface hydroxyl groups on the external surface
of CNTs and Fe
3
O
4
. The stretching vibrations at 2916 and
and C C, respectively. Ionic liquid
À1
1646 cm are related to CH
2
coating is confirmed by the appearance of two peaks at 1558 and
À1
1
042 cm corresponding to C N and Si O stretching modes,
À1
respectively. Furthermore, an intense band at 575 cm is assigned
to Fe O stretching vibration.
3 4
Scheme 1. Synthesis of 2-aminothiazoles catalysed by CNT-Fe O -IL.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

Magnetic ionic liquid in the synthesis of 2-aminothiazoles
3 4 3 4
Figure 2. SEM micrographs of (a) CNT-Fe O and (b) CNT-Fe O -IL. TEM
images of (c) CNT-Fe and (d) CNT-Fe -IL.
O
3 4
3 4
O
3 4
Scheme 2. Formation of CNT-Fe O -IL nanocomposites.
3 4
Figure 1. FT-IR spectrum of CNT-Fe O -IL.
The morphologies of CNT-Fe O and CNT-Fe O -IL nanocompos-
3
4
3 4
ites were investigated using SEM and TEM. As shown in Fig. 2(a), the
SEM image of CNT-Fe nanocomposite confirms that magnetic
3 4
O
nanoparticles grow directly with a good dispersion on the surface
of the CNTs. Figure 2(b) shows the surface morphology of
CNT-Fe
surface after coating with organosilane shell. TEM micrographs of
the CNT-Fe -IL composite compared with CNT-Fe are shown
in Figs 2(c) and (d), respectively. As shown in Fig. 2(c), the TEM
image of CNT-Fe confirms that the Fe nanoparticles are
immobilized successfully on the outer wall of CNT-COOH. In Fig. 2
d) an outer shell of the ionic liquid coated onto CNT-Fe can
3 4
O -IL, with a considerable change being observed on the
O
3 4
3 4
O
O
3 4
3 4
O
(
3 4
O
be observed. However, in some parts of the micrograph, the outer
organic shell is not detected due to the sensitivity limit of TEM.
Figure 3 shows the Raman spectra of CNT-COOH, CNT-Fe
CNT-Fe -IL nanomaterials. As shown in Fig. 3(a), two strong peaks
for CNT-COOH appear at 1307 cm (D band) and 1602 cm
G band). The ‘G’ band peak demonstrates the graphite-like tangen-
tial mode, while the ‘D’ band peak is attributed to disorder and
3 4
O and
3 4
O
À1
À1
(
Figure 3. Raman spectra of (a) CNT-COOH, (b) CNT-Fe
3 4
O and (c) CNT-
Fe O -IL.
3
4
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
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Z. Zarnegar and J. Safari
3
sp -hybridized carbon in the hexagonal framework of the CNT
walls. These two absorption peaks are weaker in the spectra of
CNT-Fe
interaction between CNT-COOH and magnetic nanoparticles.
Signals correlated to Fe for the corresponding magnetic nano-
3 4 3 4
O and CNT-Fe O -IL composites. This may be due to the
3 4
O
composites are shown by strong peaks at lower wavenumbers of
À1
about 221.02, 296.64, 401.31, 487.56 and 601.87 cm indicating
vibration modes of Fe O bonds of Fe O nanoparticles and Fe C
3
4
[
34]
bonds of CNT-Fe O nanohybrids. The similarity in the Raman
3
4
spectra of the magnetic nanocomposites suggests no structural
changes occur in the CNT-Fe O matrix after modification with
3
4
the organic groups.
Figure 4 shows the EDX patterns of CNT-Fe O and CNT-Fe O -IL
3
4
3 4
nanohybrids. The presence of C, Fe, O and Si is confirmed in the
magnetic samples. The C, Fe and O signals originate from the
magnetic component and CNT, while the Si signal comes from
the organosilane shells.
In order to analyse the phase structure, purity and crystallo-
graphic nature of the nanostructures, powder XRD studies were
used. XRD patterns of CNT-COOH, Fe O nanoparticles and the
3
4
corresponding magnetic nanocomposites are shown in Fig. 5. The
XRD diffraction pattern of CNT-COOH in Fig. 5(a) displays a strong
and sharp peak centred at 2θ = 26° representing C (0 0 2) which
is the distinguishing feature of concentric cylinders of graphitic
[35]
carbon in CNTs. This crystalline peak disappears in the patterns
of other magnetic samples. As can be seen in Fig. 5(b), characteristic
3 4
Bragg peaks for Fe O nanoparticles occur at 2θ = 26.3°, 30.5°, 35.9°,
43.6°, 54.0°, 57.5° and 63.1°, which are consistent with those found
in the Joint Committee on Powder Diffraction Standards (JCPDS)
database (PDF no. 01–1111). These are attributed to the inverse
cubic spinel structure of magnetic nanoparticles, confirming the
high purity and crystallinity of the magnetite of the sample. As
Figure 5. XRD analysis of (a) CNT-COOH, (b) Fe
CNT-Fe O -IL.
3 4
3 4 3 4
O , (c) CNT-Fe O and (d)
depicted in the diffractograms of magnetic nanostructures in Figs 5
c) and (d), the (3 1 1) peak at 2θ = 35.9° indicates the presence of
Fe in the CNT-Fe and CNT-Fe -IL nanocomposites.
Furthermore, the same characteristic peaks in the XRD pattern of
CNT-Fe -IL nanocomposite indicate that the characteristic peaks
(
O
3 4
O
3 4
3 4
O
3 4
O
do not change after coating with the organic shell, showing that
the crystalline structure and properties of the magnetite nanoparti-
cles are retained. The results confirm that the ionic liquid is success-
fully coated on the surface of CNT-Fe O .
3
4
The magnetization curves of the synthesized nanocomposites
are depicted in Fig. 6. The saturation magnetization value (M ) is
s
À1
found to be 32.0 and 24.30 emu g
for CNT-Fe O4 and
3
CNT-Fe O -IL nanomaterials, respectively. This reduction in magne-
3
4
tization value for CNT-Fe O -IL is attributed to the nonmagnetic
3
4
organic shell covering the surface of the magnetic core.
The TGA–DTA curves of CNT-Fe O4 and CNT-Fe O -IL
3
3 4
magnetic nanomaterials were obtained between 30 and
00 °C in a static atmosphere of nitrogen (Figs 7(A) and (B),
6
respectively). It is clear from a comparison of TGA curves that
for the CNT-Fe O -IL nanocomposites, there are two steps of
3
4
mass losses at temperatures of 50–200 and 200–420 °C. The
first step corresponds to the removal of physically adsorbed
water or solvent; the second step is due to the thermal
decomposition of organic moieties on the surface. The
observed total weight loss for CNT-Fe
which demonstrates that grafting of ionic liquid on the
CNT-Fe nanocomposites had been successfully achieved.
Moreover, DTA of CNT-Fe
3 4
O -IL is about 4%,
3 4
O
3 4 3 4
Figure 4. EDX characterization of (a) CNT-Fe O and (b) CNT-Fe O -IL
nanocomposites.
3
O
4
-IL indicates that the molecular
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

Magnetic ionic liquid in the synthesis of 2-aminothiazoles
Table 1. Investigation of catalytic activity of various magnetic
nanocatalysts in the reaction of acetophenone, thiourea and NBS in eth-
a
anol under reflux conditions
b
Entry
Catalyst
Time
h)
Yield (%)
(
NBS
I
2
1
2
3
4
5
6
7
8
Fe
Fe
Fe
3
O
4
4
4
3
78
85
90
82
94
88
80
78
75
83
88
78
92
85
75
72
3
O
O
@SiO
-chitosan
2
2.5
2.5
3
3
CNT-Fe
CNT-Fe
3
O
O
4
3
4
-IL
2.5
2.5
2.5
3
Fe
Fe
Fe
3
O
4
O
4
O
4
-IL
3
2 2
-SiO -TiO
3
-PEG
a
Reaction conditions: acetophenone (2 mmol), thiourea (2 mmol), I
2
or
NBS (2.5 mmol) and magnetic nanocatalyst (0.020 g) in EtOH (5 ml)
under reflux conditions.
Figure 6. Magnetization curves obtained using VSM at room temperature
for CNT-COOH, CNT-Fe O and CNT-Fe O -IL.
3 4 3 4
b
Isolated yield.
decomposition of the nanocomposite occurs in two steps at
0 and 348 °C which are followed by an exothermic process
Fig. 7). The exothermic process below 50 °C indicates a mass
5
(
loss that is attributable to the loss of adsorbed solvent from
the nanohybrids. The DTA peak at 348 °C can mainly be
attributed to the combustion of organic species in the
imidazolium ionic liquid.
Scheme 3. In situ synthesis of α-iodoketones from ketones and iodine and
HI production.
Table 2. Optimization of reaction conditions in the reaction of
a
3 4
acetophenone, thiourea and NBS catalysed by CNT-Fe O -IL
b
Entry
Catalyst (g)
Solvent (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
0.020
0.020
0.020
0.020
0.020
0.020
0.020
0.020
0.020
0.010
0.015
0.025
0.030
0.025
0.025
0.025
—
EtOH (80)
2.5
2.5
3
92
87
80
50
45
48
10
0
MeOH (65)
BuOH (118)
3
CH CN (82)
3.5
3.5
3.5
4
THF (66)
DMF (90)
Toluene (111)
CCl
CH
4
(77)
Cl (40)
4
2
2
4
0
10
11
12
13
14
15
16
17
EtOH (80)
EtOH (80)
EtOH (80)
EtOH (80)
EtOH (70)
EtOH (60)
EtOH (50)
EtOH (80)
3
75
78
96
96
85
73
68
65
2.5
2.5
2.5
2.5
2.5
2.5
4
a
Reaction conditions: acetophenone (2 mmol), thiourea (2 mmol), NBS
2.5 mmol) and solvent (5 ml), using CNT-Fe -IL.
(
b
3 4
O
Isolated yield of pure compound.
3 4
Evaluation of catalytic activity of CNT-Fe O -IL for synthesis of
2-Aminothiazoles
To initiate our study, we first tested the effect of various mag-
netic catalysts in the model reaction of acetophenone,
3 4 3 4
Figure 7. TGA–DTA curves of (A) CNT-Fe O and (B) CNT-Fe O -IL
nanohybrids.
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
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Z. Zarnegar and J. Safari
3 4
Table 3. Synthesis of 2-aminothiazole derivatives in the presence of a catalytic amount of CNT-Fe O -IL in EtOH under reflux conditions
Entry
Ketone
Product
Time (h)
Yield (%)
M.p. (°C)
Reported m.p. (°C)
[
37]
1
2
3
4
5
6
7
8
9
Acetaldehyde
3a
3b
3c
3d
3e
3f
2.5
2.5
2
90
96
97
97
92
90
92
91
92
92
89–90
93
148–150
[
2]
Acetophenone
151–153
161–162
180–183
88–91
[
17]
17]
4-Cl-acetophenone
4-Br-acetophenone
3-Me-acetophenone
162–163
[
2
181–182
[
10]
2
79–92
[
17]
38]
38]
38]
38]
2
4-NO -acetylacetone
2.5
3
285–286
177–179
225–226
148–149
219–220
286–287
[
Ethyl acetoacetate
Methyl acetoacetate
Allyl acetoacetate
Acetylacetone
3 g
3 h
3i
177–178
[
3
224–226
[
4
148–150
[
10
3j
3.5
219–220
thiourea, and I or NBS (halogenating agent) in EtOH at reflux.
2
The product 3b is obtained in 72–94% yield (Table 1) using
the various catalytic systems. CNT-Fe O -IL is the best catalyst
3
4
among the magnetic nanocatalysts. But a significant differ-
ence is observed between I2 and NBS in this reaction. All
magnetic catalysts are decomposed in the presence of I2
and not recycled. Magnetic nanoparticles such as Fe O4 and
3
nanocomposites such as Fe
acidic conditions due to the hydrogen iodide produced
Scheme 3). The recycling and reusability of catalyst are im-
3 4
O –chitosan are destroyed in
(
portant in synthetic methods. Therefore, NBS as a mild bromi-
nating agent was chosen.
The catalytic activity of CNT-Fe
model reaction under various conditions. Initially, different
solvents such as CH CN, tetrahydrofuran (THF),
dimethylformamide (DMF), toluene, CCl , CH Cl , EtOH, MeOH
3 4
O -IL was evaluated in the
3
4
2
2
and BuOH were tested, of which EtOH is the most suitable
reaction medium (Table 2, entries 1–9). It is found that the
solubility of starting materials in polar protic solvents is
important for the yield of product. Next, the effect of the
amount of magnetic nanocatalyst was also optimized. As can
be seen, when the catalyst amount is varied from 0.010 to
0
.030 g (Table 2, entries 10–13), the reaction affords the prod-
uct 3b in 75–96% yield in ethanol at reflux conditions. It is
obvious that 0.025 is the optimal amount for the
g
nanocatalyst. Furthermore, temperature is an important
parameter for achieving excellent conversion and the optimal
temperature is that of reflux (Table 2, entries 14–16). There-
fore, we conclude that 0.025 g of CNT-Fe O -IL as magnetic
organocatalyst in EtOH at reflux temperature are the most
appropriate conditions for this reaction.
Scheme 4. Suggested mechanism for the synthesis of 2-aminothiazoles
catalysed by CNT-Fe O -IL.
3 4
3
4
of oxygen atom of the carbonyl group of methylcarbonyl 1
and facilitates the formation of enolate ion 1b which converts
to α-bromomethylcarbonyl B in the media of NBS and ionic
After the optimization of key parameters, the synthetic
scope of methylcarbonyls via one-pot reaction using CNT-
Fe O -IL as a stable and efficient nanocatalyst was investi-
À
liquids. Then, free Cl ions interact with thiourea (2) acid
proton and the sulfur atom of thiourea attacks the activated
B and affords intermediate D, which would undergo an
intramolecular nucleophilic addition/dehydration process to
generate E in the presence of CNT-Fe O -IL. Next, intermedi-
3
4
gated. Ionic liquid layers on the surface of CNT-Fe O can
3
4
act as a homogeneous phase in the catalytic reaction.
Although the catalytic system is a solid, the reactant is dis-
solved in the ionic liquid phase and the system performs as
3
4
ate E undergoes neutralization reaction to furnish the desired
[39]
aminothiazole product 3b.
[
36]
a homogeneous catalyst.
The results indicate that the mag-
netic organocatalyst works efficiently with ketones having
electron-withdrawing and electron-donating substituents to
afford the corresponding 2-aminothiazoles with high yield
and purity in short reaction times (Table 3).
Conclusions
This paper has reported novel magnetic imidazolium ionic
liquid-based CNTs for the synthesis of 2-aminothiazoles. The salient
features of the research protocol include readily available starting
materials, magnetic recovery and use of NBS as a clean and mild
agent and ethanol as non-toxic solvent. The mild conditions, high
A plausible one-pot reaction pathway for the preparation of
2
-aminothiazoles in the presence of CNT-Fe
3 4
O -IL is presented
in Scheme 4. Initially, methylimidazolium ions and Fe
3 4
O
nanoparticles on CNTs as Lewis acids favour the interaction
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

Magnetic ionic liquid in the synthesis of 2-aminothiazoles
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