Magnetic core-shell titanium dioxide nanoparticles as an efficient catalyst for domino Knoevenagel-Michael-cyclocondensation reaction of malononitrile, various aldehydes and dimedone

Article abstract of DOI:10.1039/c4ra16300a

Magnetic core-shell titanium dioxide nanoparticles (Fe₃O₄@SiO₂@TiO₂) were efficiently used for the preparation of tetrahydrobenzo[b]pyran derivatives via a one-pot three component condensation reaction of variou

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Magnetic core shell titanium dioxide nanoparticles as an efficient
catalyst for domino Knoevenagel-Michael-cyclocondensation reaction of
malononitrile, various aldehydes and dimedone
Ardeshir Khazaei,*a Fatemeh Gholami,a Vahid Khakyzadeh,a Ahmad Reza Moosavi-Zare,*bJavad Afsara
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Magnetic core shell titanium dioxide nanoparticles (Fe3O4@SiO2@TiO2) was efficiently used for the
preparation of tetrahydrobenzo[b]pyran derivatives via the oneꢀpot three component condensation
reaction of various aldehydes, dimedone and malononitrile at 100 ºC under solventꢀfree conditions. The
10 catalyst was synthesized and characterized by several techniques including Xꢀray diffraction (XRD),
transmission electron microscopy (TEM), fieldꢀemission scanning electron microscope (FESEM) and
energyꢀdispersive Xꢀray spectroscopy (EDX).
Multiꢀcomponent reactions (MCRs) achieve significant role in
combinatorial chemistry due to the ability to prepare target
15 compounds with more efficiency and atomic economy by the
reaction of three or more compounds together in a single step.
Also, MCRs increase simplicity and synthetic efficiency on the
conventional organic synthesis.1–5
50
Magnetic nanoparticles (MAGNPs) can offer very promising
Scheme 1. Preparation of tetrahydrobenzo[b]pyrans.
20 properties as catalyst supports because of their large specific 55 Initially, magnetic core shell titanium dioxide nanoparticles
surface areas and magnetic properties, that facilitate the
separation of the catalyst upon reaction completion.6,7 MAGNPs
have been prepared and widely used as novel magnetically
separated catalysts in traditional metal catalyzed reactions,8
25 organocatalysis, and enzymatic catalysis.9 MAGNPs of Fe3O4 are
particularly robust, chemically stable as well as readily available
with an inherent low toxicity and cost. Preparation of them is also
generally very simple, making them an efficient and important
alternative to conventional heterogeneous catalyst supports (e.g.
30 alumina and silica).10
(Fe3O4@SiO2@TiO2) were prepared by the reaction of nanoꢀ
Fe3O4 with Tetraethyl orthosilicate and tetrabutyl titanate
respectively according the previous literature (Figure 1).23
Tetraethyl
orthosilicate
60
Tetrabutyltitanate
nano-Fe3O4
nano-Fe3O4 @ SiO2
nano-Fe3O4@SiO2@TiO2
Figure 1. Preparation of Fe3O4@SiO2@TiO2.
65 XRD pattern of the catalyst (Fe3O4@SiO2@TiO2) was studied in
a domain of 5ꢀ70 degree (Figure 2). As shown at Figure 2, XRD
patterns exhibited diffraction lines of a high crystalline nature at
about 2θ ≈ 25.3◦, 37.7◦, 48.1◦, 53.9◦, 55.0◦ and 62.7◦ which is in
good compliance with the previous literature (JCPDS 21ꢀ
The synthesis of tetrahydrobenzo[b]pyran derivatives is important
due to their significant antiꢀcoagulant, diuretic, spasmolytic, antiꢀ
cancer, and antiꢀanaphylactic properties.11 2ꢀaminoꢀ4Hꢀpyran
derivatives can be widely used as photoactive materials.12
35 Additionally, substituted 4Hꢀpyrans are observed as units in the 70 1272).24,25 Peak width (FWHM), size and inter planer distance
structure of some natural products.13,14 Several protocols have
been reported for the preparation of tetrahydroꢀ4Hꢀbenzopyran
derivatives.15ꢀ22 However, some of them suffer from the
drawbacks such as the use of toxic metals, the use of volatile
40 organic solvents, high cost and low yields.
Herein, in continuation, magnetic core shell titanium dioxide
nanoparticles (Fe3O4@SiO2@TiO2) was successfully used as
catalyst for the synthesis of tetrahydrobenzo[b]pyrans via the
oneꢀpot three component reaction of various aldehydes, dimedone
studies of the catalyst could be worked out in the 25.3 to 62.7
degree and results have been displayed in Table 1. As example,
calculations for the highest diffraction line 25.3◦ proved that an
FWHM of 0.0157 a crystallite size of the catalyst of ca. 9 nm via
75 the Scherrer equation [D =Kλ/(βcosθ)] and an Inter planer
distance of 0.3548 nm (sing the same highest diffraction line at
25.3◦) was calculated to be via the Bragg equation: dhkl =
λ/(2sinθ), (λ : Cu radiation (0.154178 nm) were obtained.
Crystallite sizes as obtained from the various diffraction lines
45 and malononitrile at 100 ºC under solventꢀfree conditions 80 using the Scherrer equation were found to be in the nanometer
(Scheme 1).
range (7.5ꢀ11.6 nm).
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30
Figure 2. XRD diagram of Fe3O4@SiO2@TiO2.
Table 1. XRD data for the catalyst (Fe3O4@SiO2@TiO2).
Peak width
[FWHM]
Size
Inter planer
Entry
2θ
[nm]
distance [nm]
1
2
3
4
5
6
25.3
37.7
48.1
53.9
55.0
62.7
0.0157
0.0122
0.0200
0.0157
0.0095
0.0139
9.0
12.0
7.5
0.3548
0.2383
0.1889
0.1699
0.1667
0.1480
35
9.9
16.4
11.6
To further prove the nanostructure of Fe3O4@SiO2@TiO2, TEM
measurements were performed as displayed in Figure 3. TEM
micrograph confirm the presence of more or less spherical
nanoparticles with a mean diameter of 9.0 nm (Figure 3).
5
10
15
40
Figure 4. FSEM micrographs of Fe3O4@SiO2@TiO2.
Energyꢀdispersive Xꢀray spectroscopy (EDX) from the obtained
nanomaterials (Figure 5) provided the presence of the expected
elements in the structure of the catalyst, namely iron, oxygen,
45 silicon, and titanium.
50
55
60
Figure 5. Energyꢀdispersive Xꢀray spectroscopy (EDX) of the catalyst.
After the characterization and identification of the catalyst, to
optimize the reaction conditions, as model reaction, the solventꢀ
free condensation of 4ꢀchlorobenzaldehyde, dimedone and
65 malononitrile was examined using different amounts of
Fe3O4@SiO2@TiO2 at range of 50–110 ºC. The best results were
obtained in the presence of 0.01 gram of Fe3O4@SiO2@TiO2 at
100 ºC. Increasing the reaction time did not improve the results
(Table 2). The model reaction was tested in the presence of SiO2,
20 Figure 3. Transmission electron micrographs (TEM) of
Fe3O4@SiO2@TiO2.
In another investigation, the FSEM micrographs of the catalyst
showed that the particles have not completely agglomerated.
Also, particles of the catalyst were observed in nano scale (Figure
25 4).
2
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Fe3O4 and TiO2 separately under optimized conditions in
comparison with Fe3O4@SiO2@TiO2. The results showed that
Fe3O4@SiO2@TiO2 is better than other catalysts in this reaction
Table 4. The solventꢀfree synthesis of tetrahydrobenzo[b]pyrans from
dimedone,
arylaldehydes
and
malononitrile
catalyzed
by
Fe3O4@SiO2@TiO2 at 95 °C.
condition (Table 2).
Table 2. Effect of different amounts of the catalyst and temperature on
the reaction between 4ꢀchlorobenzaldehyde, dimedone and malononitrile.
Yielda (%)
93
M.p. °C (Lit.)
229ꢀ230
5
Product
Time (min)
Amount of
Catalyst (g)
Temp.
(°C)
Time
(min)
Yielda
(%)
Catalyst
20
(230ꢀ231) [22]
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
0.01
0.01
0.01
50
80
90
35
20
15
65
78
85
208ꢀ210
(215ꢀ216) [22]
10
96
94
96
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
Fe3O4@SiO2@TiO
Fe3O4
SiO2
TiO2
aIsolated yield.
0.01
0.01
100
110
100
100
100
100
100
100
10
10
40
10
180
15
60
50
96
96
60
96
17
81
30
32
0.005
0.02
ꢀ
0.01
0.01
0.01
218ꢀ219
(217ꢀ218) [31]
8
5
183ꢀ186
(192ꢀ194) [32]
In the next step, the model reaction was examined using 0.01g of
Fe3O4@SiO2@TiO2 with various solvents under reflux conditions
10 in comparison with the solventꢀfree conditions. The results are
depicted in Table 3. As can be seen in Table 3, indicates that the
solventꢀfree condition was the best condition in this reaction.
250ꢀ252
(ꢀ) [35]
8
5
93
93
Table 3. Effect of different solvents of the catalyst and temperature on the
reaction between 4ꢀchlorobenzaldehyde, dimedone and malononitrile
15 under reflux condition.
Entry
Solvent
Time (min)
Yielda (%)
260ꢀ263
(252ꢀ254) [21]
1
2
3
4
Ethanol
Chloroform
Acetone
90
38
36
34
28
130
140
180
Dichloromethane
5
Acetonitrile
ꢀ
95
10
48
96
214ꢀ217
(216ꢀ217) [22]
6b
4
6
96
96
aIsolated yield. The reaction was proceeded in the absence of solvent at
b
100 °C.
To study the generality and scope of the catalyst, we extended our
study using Fe3O4@SiO2@TiO2 (0.01 g) with various aromatic
20 aldehydes to give a series of tetrahydrobenzo[b]pyran derivatives
under solventꢀfree conditions (Table 4). Various aromatic
aldehydes containing electronꢀwithdrawing substituents, electronꢀ
releasing substituents and halogens on their aromatic rings were
utilized successfully in the reaction, and obtained the
25 corresponded products in high yields and in short reaction times.
The synthesis of tetrahydrobenzo[b]pyrans was studied using
butyraldehyde as aliphatic aldehydes in the optimized condition
reaction. The expected product was obtained in 68 % of yield and
in 90 min reaction time.
30 Ethyl cyanoacetate as an active methylene compound, instead of
malononitrile, was reacted with 4ꢀchlorobenzaldehyde and
dimedone in the synthesis of pyran derivatives. In this reaction,
the desired product was prepared in 28 % of yield after 120
minutes.
207ꢀ208
(215) [13]
228ꢀ230
(228ꢀ230) [33]
6
6
97
96
150ꢀ152
(152ꢀ154) [18]
40 aIsolated yield.
35
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Table 4. Continued.
In a proposed mechanism that is shown in Scheme 2, at first,
malononitrile is reacted to carbonyl group of aldehyde which is
activated by the Fe3O4@SiO2@TiO2 to give intermediate I after
removing one molecule of H2O. Dimedone converts to enole
form after tautomerisation and attacks to cyanoolefin compound
(I) as Michael acceptor to give II. Eventually, cyclocondensation
of II produces III which is converted to desired product.
Product
Time (min)
5
Yielda (%)
96
M.p. °C (Lit.)
5
10
15
20
25
30
35
40
178ꢀ180
(186ꢀ187) [22]
N
210ꢀ212
(ꢀ) [36]
TiO2
5
98
90
C
H
C
C N
H
O
- H2O
N
C
CH2
C
216ꢀ217
(215ꢀ218) [29]
N
12
I
O
TiO2
O
N
214ꢀ216
(207ꢀ209) [30]
N
C
C
O
10
12
96
92
C
H
CH
H
O
C
C N
N
O
O
208ꢀ212
(199ꢀ201) [26]
II
TiO2
O
NH
N
C
C
200ꢀ202
(194ꢀ196) [29]
O
10
6
90
95
H
C
C
H
CH
N
C
O
N
O
202ꢀ204
(210) [13]
III
TiO2
O
NH
O
NH2
C
C
C
C
212ꢀ213
(217ꢀ218) [28]
20
88
H
C
C
N
N
O
O
217ꢀ219
(210ꢀ212) [27]
180
8
75
91
Scheme 2. Proposed mechanism for the synthesis of
45 tetrahydrobenzo[b]pyrans.
215ꢀ218
(216ꢀ218) [34]
In another study, reusability of the catalyst was tested upon the
condensation of 4ꢀchlorobenzaldehyde, (1 mmol), dimedone (1
mmol) and malononitrile (1 mmol). The reaction mixture was
extracted by warm ethanol to separate from the catalyst.
50 Afterward, the reused catalyst was used for another reaction. We
observed that the catalytic activity of the catalyst was restored
within the limits of the experimental errors for six successive runs
(Figure 5).
215ꢀ218
(208ꢀ210) [29]
8
98
95
248ꢀ250
15
aIsolated yield.
4
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Figure 5. The reaction of 4ꢀchlorobenzaldehyde, dimedone and
malononitrile in the presence of reused Fe3O4@SiO2@TiO2 at 100 °C
under solventꢀfree conditions.
5
Conclusions
In summary, we have introduced a new and highly efficient
protocol for the synthesis of tetrahydrobenzo[b]pyran compounds
by the oneꢀpot multiꢀcomponent condensation reaction of various
aldehydes, dimedone and malononitrile at 100 ºC using magnetic
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The authors gratefully acknowledge the BuꢀAli Sina University
15 Research Council and Center of Excellence in Development of
Environmentally Friendly Methods for Chemical Synthesis
(CEDEFMCS) for providing support to this work.
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aFaculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683,
20 Iran E-mail: Khzaei_1326@yahoo.com
bUniversity of Sayyed Jamaleddin Asadabadi, Asadabad, 6541835583,
Iran. E-mail: moosavizare@yahoo.com
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25 DOI: 10.1039/b000000x/
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37. General procedure for the synthesis of tetrahydrobenzo[b]pyrans
using Fe3O4@SiO2@TiO2: A mixture of dimedone (1 mmol),
malononitrile (1 mmol), aldehyde (1 mmol) and Fe3O4@SiO2@TiO2
(0.01 g) was added to a 10 mL roundꢀbottomed flask connected to a
reflux condenser and stirred in an oilꢀbath at 100 ºC. After
completion of the reaction, as monitored by TLC, the reaction
mixture was extracted with warm ethanol (10 mL) to separate the
catalyst. Crude products were soluble in warm ethanol and separated
from the catalyst. The catalyst easily collected by a magnet and
washed with ethyl acetate to reuse for another reaction. Then, the
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solid residue (crude product) was purified by the recrystallization in a
mixture of ethanol and water (9/1) to give the desired product.
6
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