MNPs@SiO2-Pr-AP: A new catalyst for the synthesis of 2-amino-4-aryl thiazole derivatives

Article abstract of DOI:10.1002/aoc.4127

A simple and efficient synthesis of 2-amino-4-aryl thiazole derivatives was carried out through the reaction of substituted acetophenones and thiourea using three different types of catalytic systems including N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide [TBBDA], poly(N,N′-dibromo-N-ethylbenzene-1,3-disulfonamide) [PBBS] and a combination of TBBDA and nano-magnetic catalyst supported with functionalized 4-amino-pyridine silica (MNPs@SiO₂-Pr-AP). The results showed that the use of TBBDA along with the MNPs@SiO₂-Pr-AP gains the highest yields of the products in the shortest reaction time.

Full text of DOI:10.1002/aoc.4127

Received: 11 July 2017
DOI: 10.1002/aoc.4127
Revised: 3 September 2017
Accepted: 10 September 2017
F U L L P A P E R
MNPs@SiO ‐Pr‐AP: A new catalyst for the synthesis of
2
2
‐amino‐4‐aryl thiazole derivatives
Ramin Ghorbani‐Vaghei
| Sedigheh Alavinia | Zohreh Merati | Vida Izadkhah
Department of Organic Chemistry, Faculty
A simple and efficient synthesis of 2‐amino‐4‐aryl thiazole derivatives was
carried out through the reaction of substituted acetophenones and thiourea
using three different types of catalytic systems including N,N,N′,N′‐
tetrabromobenzene‐1,3‐disulfonamide [TBBDA], poly(N,N′‐dibromo‐N‐ethyl-
benzene‐1,3‐disulfonamide) [PBBS] and a combination of TBBDA and nano‐
magnetic catalyst supported with functionalized 4‐amino‐pyridine silica
of Chemistry, Bu‐Ali Sina University,
6517838683, Iran
Correspondence
Ramin Ghorbani‐Vaghei, Department of
Organic Chemistry, Faculty of Chemistry,
Bu‐Ali Sina University, 6517838683, Iran.
Email: rgvaghei@yahoo.com
(
MNPs@SiO ‐Pr‐AP). The results showed that the use of TBBDA along with
2
the MNPs@SiO ‐Pr‐AP gains the highest yields of the products in the shortest
2
reaction time.
KEYWORDS
2‐Amino‐4‐aryl thiazole, magnetic nanoparticles, nano catalyst, solvent‐free, thiourea
1
| INTRODUCTION
environmental impact of the synthesis of thiazoles is of
interest and still in much demand.
The synthesis of organic compounds via green, mild, and
simple procedures is currently receiving considerable
attention of chemists. In recent years, the solvent‐free
organic reactions have captured great interests owing to
their many advantages including high efficiency and
selectivity, easy separation and purification, mild reaction
conditions, reduction in wastes, and benefits to the indus-
Metal oxide nanostructures such as iron, have gained
significant importance as they have been demonstrated
to be applicable in catalytic technology which cannot be
[
11]
usually achieved by their bulk counterparts.
In contin-
uation of our research in the field of application of metal
nanoparticles as heterogeneous catalysts in organic
12a–c
reactions,
in this study, three convenient methods
[1]
try and environment. In recent decades, heterocyclic
compounds have attracted much attention because of
their abundance, and their increasing importance in the
for the one‐pot synthesis of 2‐amino‐4‐aryl thiazole
derivatives from substituted acetophenones and thiourea
are described in which TBBDA, PBBS, or a combination of
TBBDA and magnetic nanoparticles supported with
[2]
[3]
field of pharmaceuticals and chemical industries. Thi-
azole and its derivatives have been shown to possess a
broad range of biological activities. For example, thiamine
functionalized 4‐amino‐pyridine silica (MNPs@SiO
are investigated as catalytic systems.
‐Pr‐AP)
2
is known as vitamin B , Ritonavir is an anti‐HIV agent,
1
and Nizatidine is an anti‐acid agent for the treatment of
gastroesophageal reflux disease (Figure 1). Hantzsch,
2
2
| EXPERIMENTAL
[4]
Tchernic, Cook‐Heilborn, and Gabriel methods are some
.1 | Materials and instrumentation
[
5]
common routes for the preparation of thiazoles. Till
now, these methods have been accomplished using differ-
All commercially available chemicals were obtained
from Merck and Fluka companies and used without
further purification otherwise stated. Nuclear magnetic
[6]
ent catalysts such as Bismuth chloride, ammonium‐12‐
[
7]
[8]
[9]
molybdophosphate, cyclodextrin, I , and I with
nanochitosan.
2
2
[10]
Therefore, further development on the
resonance (NMR) spectra were recorded in DMSO‐d on
6
Appl Organometal Chem. 2017;e4127.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 10
https://doi.org/10.1002/aoc.4127

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GHORBANI‐VAGHEI ET AL.
for 30 min in a mixture of ethanol (20 mL), deionized
water (80 mL), and ammonia solution (4.0 mL, 25% in
water) using an ultrasonic treatment. Then, tetraethyl
orthosilicate (11 mmol, 2.0 mL) was poured into the
mixture and stirred for 3 h at room temperature. The
resultant products were carefully washed with deionized
water and then twice with ethanol and dried at 60 °C
under vacuum condition.
To modify the silica surface, MNPs@SiO (1.0 g) was
2
dispersed in dry toluene (50 mL) for 30 min under reflux
condition, and then 3‐chloropropyltriethoxy silane
FIGURE 1 The structure of some biologically active thiazole
(
CPTS, 2 mL) was gradually added to it. The mixture
derivatives
was refluxed for 24 h and then, the solid MNPs@SiO2‐
Pr‐Cl was filtered off, washed with toluene using a Soxhlet
apparatus, and dried at 60 °C under vacuum condition.
To prepare 4‐amino‐pyridine functionalized silica,
Bruker Avance spectrometers of 250 MHz, 400 MHz and
1
5
00 MHz for H NMR and 62.5, 100 and 125 MHz for
C NMR using TMS as an internal standard; chemical
1
3
MNPs@SiO ‐Pr‐Cl (1.0 g) was dispersed in dry DMF
2
shifts were expressed in parts per million (ppm). Infrared
IR) spectroscopy was conducted on a Perkin Elmer GX
(
50 mL) and 4‐aminopyridine (10 mmol, 0.94 g) was added
(
to it at 90 °C. The reaction mixture was stirred well and
FT‐IR spectrometer. Mass spectra were recorded on a
Shimadzu QP 1100 BX Mass Spectrometer. Melting points
were determined on a Stuarf Scientific SMP3 apparatus.
PowderX‐ray diffraction (PXRD) patterns recorded on a
Rigaku XDS 2000 diffractometer using nickel‐filtered
CuKa radiation (λ =1.5418) over a range of <50°.
Thermo‐gravimetric analysis (TGA) was performed on a
PYRIS DIAMOND instrument. Energy dispersive X‐ray
analysis of the prepared catalyst was performed on a
FESEM‐SIGM (Germany) instrument. Scanning electron
microscopy (SEM) was performed on EM3200 instrument
operated at 30 kV accelerating voltage. Elemental analy-
ses (C, H, N) were obtained on a Thermoquest Flash
EA1112 CHN corder, made in Thermofinnigan company
in Italy. The analysis was repeated two times and the aver-
age of results has been displayed.
heated under reflux conditions for 2 days. The solid phase
(
MNPs@SiO ‐Pr‐AP) was separated using an external
2
magnet, washed with DMF using a Soxhlet apparatus,
and dried at 60 °C under reduced pressure. The synthesis
procedure for the MNPs@SiO ‐Pr‐AP is illustrated in
2
Scheme 1.
2.3 | General procedure for the synthesis
of 2‐amino‐4‐aryl thiazoles (method a)
A mixture of substituted acetophenone (1 mmol), thio-
urea (0.15 g, 2 mmol) and TBBDA (0.15 g, 0.25 mmol)
or PBBS (0.2 g) was heated under stirring at 120–140 °C
for appropriate times as shown in Table 3. The progress
of reaction was monitored by TLC (10:3, n‐hexane/ace-
tone). After completion of the reaction, the reaction
mixture was allowed to cool to room temperature, the
product was dissolved in boiling water and extracted with
EtOAc (3 × 10 mL) for three times and adjusted to pH = 10
to gain the pure product. The pure product was achieved
by crystallization from ethanol.
2.2 | Preparation of magnetic
nanoparticles (MNPs) supported with
functionalized 4‐aminopyridine
(
MNPs@SiO ‐Pr‐AP)
2
Fe O MNPs were prepared through the co‐precipitation
3
4
2
.4 | Promoted procedure for the
synthesis of 2‐amino‐4‐aryl thiazoles
method B)
[13]
technique described before in literature.
Briefly, FeCl3
(3 mL, 2 M dissolved in 2 M HCl) was added to double
(
distilled water (10.33 mL) followed by dropwise addition
of Na SO (2 mL, 1 M) for 3 min under magnetic stirring.
A mixture of substituted acetophenone (1 mmol), thiourea
(0.15 g, 2 mmol) and TBBDA (0.15 g, 0.25 mmol) was
heated in the presence of MNPs@SiO ‐Pr‐AP (0.03 g) as
2
3
The solution color changed from red to light yellow, then,
NH .H O solution (80 mL, 0.85 M) was added to it under
3
2
2
severe stirring. After 30 min, the obtained MNPs were
separated using an external magnet and then washed with
distilled water to reach pH < 7.5.
the catalyst at 80 °C. The reaction progress was monitored
by TLC (10:3, n‐hexane/acetone). After completion of
the reaction, the mixture was dissolved in boiling water
(30 mL) and the nanocatalyst was separated using an
external magnet. Subsequently, EtOAc (10 mL) was added
MNPs@SiO2 was synthesized through a modified
[13]
method of Stöber.
MNPs (4.3 mmol, 1 g) was dispersed

GHORBANI‐VAGHEI ET AL.
3 of 10
SCHEME 1 The synthetic route of
nanocatalyst
and extracted for three times and adjusted to pH = 10
to obtain the pure product. The MNPs@SiO ‐Pr‐AP was
2
reused for at least four times and separated using an
external magnet. The catalyst was recovered by washing
with ethyl acetate and then dried at 50–60 °C in an oven
to be used for four times. The spectral data of some
synthesized compounds are provided in Supporting
information.
2.5 | Selected spectral data of thiazole
derivatives (Table 3)
4
2
‐(3,4‐Dimethoxyphenyl)thiazol‐2‐amine (3j), Mp: 290‐
92 °C. Yield: 70%. IR (KBr): 3411, 3316, 1637 cm . H
FIGURE 2 The structure of TBBDA, PBBS and MNPs@SiO2‐
Pr‐AP
−1 1
NMR (400 MHz, DMSO‐d ): δ (ppm) 3.61 (s, 3H, OCH ),
6
H
3
3
.63 (s, 3H, OCH ), 6.7 (s, 1H, thiazole H), 6.7 (dd, 1H,
3
3
| RESULTS AND DISCUSSION
J = 8.4 Hz, J = 9.2 Hz), 6.9 (s, 2H, NH ), 7.16 (dd, 1H,
J = 1.6 Hz, J = 3.2 Hz) 7.19 (d, 1H, J = 0.8 Hz). C NMR
2
13
As a part of our previous research in the synthesis of hetero-
cyclic compounds using TBBDA and PBBS (Figure 2),
herein, we describe a new and efficient method for the
one‐pot synthesis of 2‐amino‐4‐aryl thiazole derivatives
through the condensation of substituted acetophenones
with thiourea in the presence of TBBDA, PBBS, or
(62.5 MHz, DMSO‐d ): δ :55.8, 56.1, 99.4, 109.1, 111.9,
6
c
1
2d–e
1
2
1
17.8, 128.7, 144.0, 147.7, 149.8, 167.9 ppm. MS:(m/z):
36. Anal. Calcd for C H N O S: C, 55.92; H, 5.12; N,
11
12
2 2
1.86. Found: C, 55.91; H, 5.10; N; 11.47.
‐(2‐Amino thiazol‐4‐yl)benzonitrile (3 k), Mp: 220 °C.
4
−
1 1
Yield: 75%. IR (KBr): 3439, 3360, 2155, 1634 cm . H
NMR (250 MHz, DMSO‐d ): δ (ppm) 6.7 (s, 1H, thiazole
H), 7.44 (s, 2H, NH ), 7.81 (d, 2H, J = 8.25 Hz), 7.93 (d,
MNPs@SiO ‐Pr‐AP/TBBDA (Scheme 2).
2
6
H
Initially, MNPs@SiO2 was synthesized through a
2
3
[13]
1
modified method of Stöber,
and subsequently, it was
2
1
H, J = 8.5 Hz), C NMR (62.5 MHz, DMSO‐d ): δ :
6
c
05.5, 110.8, 119.1, 128.9, 132.7, 137.9, 150.1, 167.8 ppm;
MS (m/z): 201.
‐(2‐Amino‐5‐chlorophenyl)thiazol‐2‐amine (3 l), Mp:
4
−
1
2
46 °C. Yield: 70%.IR (KBr): 3439, 3360, 2155, 1634 cm .
1
H NMR (250 Hz, DMSO‐d ): δH (ppm) 7.0 (dd, 3H, CH
6
and NH , J = 7.25, 10.25 Hz), 7.3 (s, 3H, thiazole H and
2
13
NH ), 7.5 (d, 1H, J = 7.25 Hz), 8.0 (s, 1H), C NMR
2
(
62.5 MHz, DMSO‐d ): δ : 107.9, 113.0, 118.0, 124.2,
SCHEME
2
One‐pot synthesis of 2‐amino‐4‐arylthiazole
6
c
1
28.8, 128.9, 143.7, 150.9, 168.3 ppm; MS (m/z): 225.
derivatives

4
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GHORBANI‐VAGHEI ET AL.
FIGURE 3 XRD patterns of a) MNPs, b) MNPs@SiO
MNPs@SiO ‐Pr‐Cl and d) MNPs@SiO ‐Pr‐AP
2
, c)
2
2
2
FIGURE 6 (a) TGA and DTA curves of MNPs@SiO ‐Pr‐AP and
(
b) TGA curve of MNPs@SiO
2
‐Pr‐Cl
functionalized
with
4‐aminopyridine
to
gain
MNPs@SiO ‐Pr‐AP. The catalyst was first characterized
2
by XRD analysis (Figure 3). Considering the XRD pat-
terns, the intensity ratio of the main peak recognized at
2θ = 35.60° which is present in all patterns of MNPs,
2
FIGURE 4 SEM image of MNPs@SiO ‐Pr‐AP
MNPs@SiO , MNPs@SiO ‐Pr‐Cl and MNPs@SiO ‐Pr‐AP
2
2
2
confirms the existence of MNPs in all samples. The XRD
patterns of the samples also display six characteristic
peaks related to a cubic iron oxide phase (2θ = 30.10,
3
5.50, 43.10, 53.00, 57.00, and 62.80). These peaks are
exposed to their corresponding indices including (2 2 0),
3 1 1), (4 0 0), (3 3 1), (4 2 2) and (5 1 1), respectively. It
(
is understood that the resultant MNPs with a spinel struc-
ture and that the grafting process did not change the
phase of Fe O .
3
4
The SEM image of MNPs@SiO ‐Pr‐AP was studied to
2
determine the particles' size. Figure 4 clearly shows the
dimensions and shapes of the particles. According to the
particles' size obtained by the SEM mages (41–83 nm), it
is illustrated that our method for the synthesis of
MNPs@SiO ‐Pr‐AP was a successful procedure. Addition-
2
ally, EDX analysis of the catalyst confirms the presence of
C, N, Fe, O and Si atoms on the structure and the peak
appeared at 2.2 corresponds to Au atom. The observed
Au element is due to the coating of sample with a gold
layer (Figure 5).
The TGA and DTA curves (Figure 6) were applied for
MNPs@SiO ‐Pr‐AP and MNPs@SiO ‐Pr‐Cl to investigate
2
2
FIGURE 5 EDX analysis of MNPs@SiO
2
‐Pr‐AP
the thermal stability/degradation and to determine the

GHORBANI‐VAGHEI ET AL.
5 of 10
TABLE 1 Optimizing the reaction conditions for the synthesis of 2‐amino‐4‐phenyl thiazole 3a
a
b
Entry
Catalyst
Conditions
Time (h)
Yield (%)
1
‐
120 °C
6
‐
2
3
4
5
6
7
8
9
TBBDA (0.2 mmol)
TBBDA (0.25 mmol)
TBBDA (0.5 mmol)
PBBS (0.2 g)
120 °C
120 °C
120 °C
120 °C
100 °C
80 °C
2.5
2.5
2.5
4
64
78
68
60
c
MNPs@SiO
2
‐Pr‐AP (0.05 g)
24
2
0
TBBDA (0.25 mmol)/pyridine (1 mmol)
TBBDA (0.25 mmol)/NaOAc (1 mmol)
TBBDA (0.25 mmol)/NaOH (1 mmol)
85
80 °C
2
Trace
Trace
Trace
85
80 °C
2
10
11
12
13
14
15
16
17
TBBDA (0.25 mmol)/CH
3
COOH (1 mmol)
100 °C
80 °C
2
TBBDA (0.25 mmol)/MNPs@SiO
TBBDA (0.25 mmol)/MNPs@SiO
TBBDA (0.25 mmol)/MNPs@SiO
TBBDA (0.25 mmol)/MNPs@SiO
TBBDA (0.25 mmol)/MNPs@SiO
2
2
2
2
2
‐Pr‐AP (0.01 g)
‐Pr‐AP (0.02 g)
‐Pr‐AP (0.03 g)
‐Pr‐AP (0.04 g)
‐Pr‐AP (0.03 g)
2.5
2
80 °C
88
80 °C
1
91
80 °C
1.5
1
90
100 °C
80 °C
90
NBS (1.2 mmol)/ MNPs@SiO
HBr
2
‐Pr‐AP (0.03 g)
3
52
c
100 °C
24
0
a
Reaction condition: acetophenone (1 mmol), thiourea (2 mmol), solvent‐ free.
b
Isolated yield.
c
No reaction.
content of organic groups loaded on the surface. The first
change in both TGA and DTA around 100 °C is due to the
loss of adsorbed water on the surface of silica. After this
temperature, around 5% weight loss is observed in the
temperature range of 100–500 °C confirming 0.8 mmol/g
product (Table 1, entry 4). It is assumed that increasing
the amount of TBBDA results in increasing the concentra-
tions of bromide which as a result, alpha‐bromination
reaction may happen twice instead of once. Also, bromi-
nation of aromatic ring may result in the formation of
byproducts which results in decreasing the reaction yield.
Since the results from TBBDA were better than those of
PBBS (Table 1, entries 3 and 5), we evaluated the effect
of a secondary catalyst along with TBBDA (Table 1,
of organic groups were loaded on the MNPs@SiO surface
2
(
Figure 6a). The TGA analysis of MNPs@SiO ‐Pr‐Cl was
2
provided to compare the loading of organic substances
on the two surfaces (Figure 6b). As it is shown in
Figure 6a, b the two diagrams are different. Additionally,
the presence of nitrogen in EDX analysis of the final prod-
uct proves the substitution of amino‐pyridine in
MNPs@SiO2.
entries 7–15) and it was found that MNPs@SiO ‐Pr‐AP
2
was more active than other catalysts (Table 1, entry 13).
It was observed that the base, salt or organic acid inacti-
vate TBBDA. Acetic acid makes thiourea inactive and
results in trace yield of product. NaOH results in the prep-
aration of BrOH which inactivates TBBDA. NaOAc forms
BrOAc and inactivates TBBDA. But pyridine activates
Then, the effect of TBBDA and PBBS as reagent and
MNPs@SiO ‐Pr‐AP as catalyst were investigated in the
2
synthesis of the model compound 2‐amino‐4‐phenyl thia-
zole 3a. First, the reaction progress was examined in the
absence of catalyst and it was observed that the reaction
could not proceed without the catalyst even after a
prolonged reaction time (Table 1, entry 1). We also evalu-
ated the amount of catalyst required for this transforma-
tion. It was determined that using 0.25 mmol of TBBDA
is sufficient to push the reaction forward (Table 1, entry
TABLE 2 Optimizing the molar ratio of acetophenone/thiourea
for the synthesis of 2‐amino‐4‐phenyl thiazole 3a using TBBDA
Molar ratio of
Time Yield
Entry acetophenone/thiourea Conditions (h)
(%)
1
2
3
4
1/1
120 °C
120 °C
120 °C
120 °C
3
58
1/1.5
1/2
2.5
2.5
2.5
65
78
73
3
), meanwhile less than 0.25 mmol of the TBBDA leads
to the low reaction yield (Table 1, entry 2). In addition,
more amount of TBBDA did not increase the yield of
1/2.5

6
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GHORBANI‐VAGHEI ET AL.
a
2
TABLE 3 Synthesis of 2‐amino‐4‐aryl thiazoles 3a–l using TBBDA, PBBS or MNPs@SiO ‐Pr‐AP/TBBDA
TBBDA
PBBS
MNPs@SiO
2
‐Pr‐AP/TBBDA
Yield (%)
b
b
b
Ref
Entry Product
Time (h) Yield (%) Time (h) Yield (%) Time (h)
m.p.
m.p.
[
14]
1
2.5
2.5
78
85
4
60
70
1
91
150–151 148–150
[
[
[
[
[
14]
14]
14]
14]
15]
2
3
4
5
6
4
1
95
207–208 203–205
2.5
2.5
2.5
3
90
65
78
70
4
78
50
55
60
1
98
79
90
82
285–287 283–285
200–201 200–203
135–136 130–132
285–286 282–283
4
1.5
1.5
1.5
3.5
5
[
14]
7
8
2
3
87
73
3
4
70
70
1
96
88
227–230 227–230
[
16]
1.5
195–196 200
(Continues)

GHORBANI‐VAGHEI ET AL.
7 of 10
TABLE 3 (Continued)
TBBDA
PBBS
MNPs@SiO
2
‐Pr‐AP/TBBDA
Yield (%)
b
b
b
Ref
Entry Product
Time (h) Yield (%) Time (h) Yield (%) Time (h)
m.p.
m.p.
[
14]
9
2.5
60
55
4
55
50
1.5
77
178–180 175–177
[
17]
1
0
4
5.5
1.5
70
290–292 198–201
[
18]
1
1
1
2
3
5
65
65
5
65
60
2.5
75
70
220
246
222–224
6.5
2
New
a
Reaction condition: acetophenone (1 mmol), thiourea (2 mmol), solvent‐free.
b
Isolated yield.
TBBDA due to the formation of pyridinium bromide ion
pair. The model reactions carried out by using other cata-
The effect of the reaction time on the modal reaction
was investigated (Figure 7). It was determined that the
highest conversation yield (91%) was obtained after 1 h
on method B vs. highest conversion yield (78%) was
obtained after 2.5 h on method A. It was concluded that
method B results in the highest yields of the products in
a shorter reaction time.
The effect of different substituted acetophenones on
the reaction yield based on methods A and B is depicted
in Figures 8 and 9. It is concluded from Figure 8 that
when method B is used, excellent yields of 2‐amino‐4‐aryl
thiazoles were obtained with substituted acetophenones
containing electron‐withdrawing groups. Similarly, the
results of Figure 9 show that 4‐methoxyacethophenone
gives the desired products in a lower yield in the presence
of method A. The results also show that the use of TBBDA
lysts such as NBS/MNPs@SiO ‐Pr‐AP and HBr showed
2
that they did not avail against the reaction (Table 1,
entries 16–17).
Then, different molar ratio of acetophenone and thio-
urea were tested in this reaction. The corresponding prod-
uct was obtained in excellent yield under solvent‐free
conditions at 120 °C when the molar ratio of
acetophenone and thiourea was 1:2 (Table 2, entry 3) with
either 0.25 mmol of TBBDA or 0.2 g of PBBS (Table 1,
entries 3 and 5, respectively). The generality of this pro-
cess was demonstrated by a wide range of substituted
acetophenones for the synthesis of 2‐amino‐4‐aryl thia-
zole derivatives (Table 3). It was observed that para‐
substituted acetophenones containing electron‐withdraw-
ing groups afforded 2‐amino‐4‐aryl thiazoles in excellent
yields while the yield of corresponding products
decreased by using substituted acetophenones containing
electron‐donating groups.
together with MNPs@SiO ‐Pr‐AP gains the products in
2
the highest yields within a short reaction time.
Literature surveys revealed that various conditions
have been employed in this reaction. As demonstrated in

8
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GHORBANI‐VAGHEI ET AL.
FIGURE 7 The effect of reaction time
on the modal reaction on methods A
(
TBBDA) and B (MNPs@SiO
2
‐Pr‐AP/
TBBDA)
FIGURE 8 Effects of substituents on kinetics of the reaction of substituted acetophenones with thiourea on method B (TBBDA/
MNPs@SiO ‐Pr‐AP, solvent‐free, 80 °C)
2
FIGURE 9 Effects of substituents on kinetics of substituted acetophenone with thiourea on method A (TBBDA, solvent‐free, 120–140 °C)

GHORBANI‐VAGHEI ET AL.
9 of 10
TABLE 4 Comparison of different methods in the synthesis of 2‐amino‐4‐phenyl thiazole 3a
Entry
Catalyst
Solvent
Conditions
Time (h)
Yield (%)
Ref.
[
[
[
[
[
19]
19b]
20]
21]
10]
1
I
I
I
I
2
2
2
2
‐
MW
6–10 min
88–92
2
3
4
5
6
‐
140 °C
Reflux
Reflux
Reflux
80 °C
2
65
96
90
95
91
NH
3
.H
2
O
4
/CuO
EtOH
EtOH
‐
‐‐‐
2.5
1
Nanochitosan, I
2
MNPs@SiO ‐Pr‐AP/TBBDA
2
This work
increase the yield of product. In the next step, the catalytic
activity and reusability of MNPs@SiO ‐Pr‐AP for the
2
synthesis of the model compound 2‐amino‐4‐phenyl
thiazole 3a was evaluated up to four consecutive
implementations (Figure 10). The catalyst was recovered
by washing with ethyl acetate then dried at 50–60 °C in
an oven to be used for four times. The results showed a
slight loss of activity even after four implementations
(
91, 88, 85 and 84, respectively).
The proposed mechanism is shown in Scheme 3.
Initially, MNP@SiO ‐Pr‐AP activates acetophenone 1 and
2
FIGURE 10 Reusability of MNPs@SiO
of 2‐amino‐4‐arylthiazole 3a
2
‐Pr‐AP for the synthesis
converts it to the enolated form 4. The latter then attacks
to the bromide ion of TBBDA following by a nucleophilic
addition of activated thiourea 6 from its S‐head to
afford the intermediate 7. Intramolecular cyclization of
intermediate 7 leads to the formation of 2‐amino‐4‐aryl
Table 4, iodine has been used as catalyst under different
conditions to proceed the reaction. While in the current
work, the use of TBBDA along with the MNPs@SiO ‐Pr‐
2
[
12]
AP can significantly improve the reaction time and
thiazole 3.
Correspondingly, through this process,
2
SCHEME 3 Suggested mechanism for the synthesis of 2‐amino‐4‐arylthiazole derivatives in the presence of TBBDA and MNP@SiO ‐Pr‐AP

10 of 10
GHORBANI‐VAGHEI ET AL.
TBBDA losses a bromine atom and obtains a proton from
the protonated catalyst. Accordingly, the latter may be
attacked by another acetophenone enolate 4 and losses
another bromine atom. This cycle is continued to lose all
bromine atoms.
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| CONCLUSION
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In conclusion, the magnetically recoverable MNP@SiO2‐
Pr‐AP was synthesized and characterized using different
techniques. It was demonstrated that the use of TBBDA
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Appl. Organomet. Chem. 2015, 29, 195; (b) R. Ghorbani‐Vaghei,
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Ozturk, Appl. Organomet. Chem. 2015, 29, 26; (d) R.
Ghorbani‐Vaghei, Y. Maghbooli, Synthesis 2016, 48, 3803; (e)
R. Ghorbani‐Vaghei, S. M. Malaekehpoor, Synthesis 2017, 49,
along with the MNP@SiO ‐Pr‐AP catalyzed efficiently
2
the reaction of substituted acetophenones with thiourea
under solvent‐free conditions to gain 2‐amino‐4‐aryl thia-
zole derivatives in high yields and short reaction times.
This method provides advantages including recyclability
of the catalyst (MNP@SiO ‐Pr‐AP), availability of the
reactants and simple procedure of the reactions.
763.
2
[
[
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ACKNOWLEDGEMENTS
[
15] M. R. Bodireddy, P. M. Khaja Mohinuddin, T. R. Gundala, N.
We are thankful to Bu‐Ali Sina University, Center of
Excellence in Development of Environmentally Friendly
Methods for Chemical Synthesis (CEDEFMCS) for
financial support.
Gangi Reddy, Cogent Chem. 2016, 2, 1154237.
[
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