A unique approach to magnetization of metal oxides: Nano-Fe3O4@TDI@TiO2 as a highly efficient, magnetically separable and recyclable heterogeneous nanocatalyst

Article abstract of DOI:10.1039/c6cy00316h

A highly efficient and magnetically recyclable nanocatalyst has been prepared by covalent grafting of Fe₃O₄ and TiO₂ nanoparticles to 2,4-toluene diisocyanate as an inexpensive and highly reactive linker. The morphology an

Full text of DOI:10.1039/c6cy00316h

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Catalysis Science & Technology
ARTICLE
A unique approach to magnetization of metal oxides: Nano-
Fe3O4@TDI@TiO2 as a highly efficient, magnetically separable and
recyclable heterogeneous nanocatalyst
Received 00th January 20xx,
Accepted 00th January 20xx
Elham Tabrizian and Ali Amoozadeh*
DOI: 10.1039/x0xx00000x
A highly efficient and magnetically recyclable nanocatalyst has been prepared by covalent grafting of Fe3O4 and TiO2
nanoparticles to 2,4-toluene diisocyanate as an inexpensive and highly reactive linker. The morphology and structure of this
novel nanocatalyst was investigated by Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron
microscopy (FE-SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM).
The catalytic activity of the catalyst was probed for the synthesis of tetrahydrobenzo[b]pyran and hexahydroquinoline
derivatives at 70 °C under solvent-free conditions with excellent yields and short reaction times. Experimental design was
adopted to optimize the reaction conditions by central composite design (CCD). The catalyst can be readily separated
by applying an external magnet device and recycled up to 6 times without significant decrease in catalytic activity, which
makes it highly beneficial to address the industrial needs and environmental concerns. This is the first study that reports a
unique method for magnetization of metal oxides through the usage of TDI as a linker and creating a nanocatalyst by
covalent grafting of two metal oxides. Moreover, this method could be extended to link other different metal oxides too as
well as the magnetic ones.
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Titanium dioxide nanoparticles (nano-TiO2) are certainly one of
the most interesting metal oxides due to their easy availability, non-
toxicity, high activity, reusability, strong oxidizing power and long-
term stability.8, 9 It has been proved that nano-TiO2 is an efficient
Lewis acid catalyst for the synthesis of wide variety of heterocyclic
and organic compounds.8, 10-12 Moreover, it is a well-known matter
used for photo-electrochemical cell, water or air purification and
degrading the organic pollutants.
Considering the high catalytic activity of n-TiO2 and n-Fe3O4 and
the magnetic properties of n-Fe3O4, we have decided to couple these
catalysts through a linker in order to synthesize an easy separable
nanocatalyst with improved catalytic property, hence we have
applied 2,4-toluene diisocyanate (TDI) as a coupling agent which is a
kind of bifunctional-group organic chemicals. TDI is readily available,
low-cost, and very active due to its highly unsaturated bonds.
Furthermore, the reaction between metal oxides and TDI could occur
fast, easily and without any catalyst. To the best of our knowledge,
there are no literature reports on applying TDI as a linker to join two
different metal oxides. So we have decided to estimate the catalytic
applicability of the prepared catalyst for synthesizing
tetrahydrobenzo[b]pyrans and hexahydroquinolines. It is notable
that, this novel strategy opens up avenues for design and engineering
1. Introduction
Catalysis is a core area of contemporary science posing major
fundamental and conceptual challenges. Nowadays, synthetic
chemists focused on the preparation, characterization and use of
reusable, easily separable, non-toxic and low-cost catalysts as a
major issue of modern chemistry and the use of nanoparticles as
heterogeneous catalysts has attracted considerable attention due to
their interesting structural features, high levels of activity and
enhanced selectivity. Among them, nano metal oxides have been
widely applied as efficient catalysts for various synthetic organic
transformations due to their high surface area-to-volume ratio and
coordination sites which are mainly responsible for their catalytic
activity.1, 2
Magnetic Fe3O4 nanoparticles are a class of nanostructured
metal oxides which are widely applied in various fields, such as
magnetic resonance imaging (MRI) contrast agents, magnetically
assisted drug delivery and hyperthermia.3, 4 Particularly, they have
emerged as a useful heterogeneous catalyst in many organic
transformations due to low toxicity, high surface area and large
surface-to-volume ratio.5-7 Notably, the insoluble and paramagnetic
nature of the Fe3O4 enable trouble-free separation of this
nanocatalyst from the reaction mixture by using an external magnet,
which eliminates the necessity of catalyst filtration.
a
wide variety of new and interesting nanomaterials and
nanocatalysts.
2. Result and Discussion
As part of our efforts in exploring heterogeneous catalysts for organic
reactions,13-18 we have designed, prepared and characterized nano-
a. Department of Organic Chemistry, Faculty of Chemistry, Semnan University,
Semnan 35131-19111, Iran.
Electronic Supplementary Information (ESI) available: [FT-IR, 1HNMR and 13CNMR
spectra]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Fe3O4@TDI@TiO2 as a highly efficient, magnetically separable and cm-1 is related to the phenyl ring of TDI. These results suggested that
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DOI: 10.1039/C6CY00316H
recyclable nanocatalyst as a novel class of heterogeneous catalysts TDI was successfully anchored on the surface of Fe3O4 nanoparticles.
(Scheme 1).
In curve e, the fingerprinting IR bands at the range of 500-700 cm-1
shows a bit difference from the Fe-O vibration band at 578 cm-1
(curve a), which is ascribed to Ti-O stretching and Ti-O-Ti bridging
stretching modes28 and proves loading of n-TiO2 onto the surface of
n-Fe3O4@TDI. Moreover, the isocyanate peak at 2262 cm-1 is
disappeared. Thus, the deposition of TiO2 nanoparticles on n-
Fe3O4@TDI is certainly achieved.
Scheme 1. Preparation of Fe3O4@TDI@TiO2 nanocatalyst.
As illustrated in Scheme 1, at the first step, Fe3O4 nanoparticles
were synthesized by co-precipitation method according to the
literature report.19 Subsequently, n-Fe3O4 was treated with excessive
TDI in which accessible surface hydroxyls of n-Fe3O4 favorably
reacted with para-isocyanate groups of TDI through the formation of
urethane bonds,20, 21 leaving the ortho-isocyanate groups unreacted
due to the different reactivity of the two isocyanate groups together
with steric hindrance in TDI molecule.22 Then, n-TiO2 which was
previously synthesized considering the literature report,23 was added
and similarly the surface hydroxyl groups of n-TiO2 reacted with the
unreacted ortho-isocyanate groups of n-Fe3O4@TDI, however in
higher temperature and longer reaction time. It is worth noting that,
due to presence of adsorbed water on the surface of almost all
nanomaterials, especially oxides, there might be some free primary
amino groups present on the surface of the nanocatalyst.
This novel nanocatalyst was characterized via FT-IR, FE-SEM,
XRD, TGA, and VSM analyses.
Figure 1. FT-IR spectra of (a) n-Fe3O4, (b) n-TiO2, (c) TDI, (d) n-Fe3O4@TDI, (e) n-
Fe3O4@TDI@TiO2.
2.1. Characterization of n-Fe3O4@TDI@TiO2
FT-IR spectra
Fourier transform infrared spectroscopy (FT-IR) is one of the best
techniques to characterize the functionalization of nanoparticles. So,
FT-IR spectra of the n-Fe3O4 and every step of the reaction was
analyzed (Fig. 1). In curve a, the adsorption peaks appearing at 578
and 626 cm−1 correspond to the Fe-O bands and broad peaks at
3000–3600 cm−1 and 1623 cm−1 are respectively attributed to the
stretching and bending modes of the O–H of surface hydroxyl groups
and physically adsorbed water.24 In curve b, for n-TiO2, the broad
intense band below 1200 cm−1, that is considered as the fingerprint
of the TiO2, is attributed to Ti-O-Ti vibration and the absorbance at
1623 and 3355 cm−1 are assigned to the surface hydroxyl groups of
TiO2.25 Curve c in Fig. 1 shows the FT-IR spectrum of TDI. The
absorption peak at 2243 cm-1 owing to stretching vibration of NCO,
which agrees with the literature values,26 is its main peak. The peaks
at 1550 cm-1 are reasonably attributed to the phenyl ring of TDI. FT-
IR spectrum of TDI-functionalized n-Fe3O4 (Fig. 1d), compared with
the spectrum of the bare Fe3O4 nanoparticle (Fig. 1a), is revealed new
peaks at 2262, 1647, 1595, and 1539 cm-1. The peak at 2266 cm-1 can
be attributed to the unreacted ortho-isocyanate groups of TDI
attached to the n-Fe3O4 surface, while the bands at 1647 and 1595
cm-1 can be assigned to the C=O and C-N stretches indicating that the
reaction of toluene diisocyanate with n-Fe3O4 takes place through
the formation of a urethane bond (OCONH)27 and the N-H bond of
urethane at 3267 cm-1 may overlapped with broad peaks of surface
hydroxyl groups and adsorbed water. Additionally, the peak at 1539
Thermo gravimetric analysis
One indication of bond formation between the nanoparticles and the
TDI can be inferred from thermogravimetric analysis (TGA). Fig. 2
shows thermogravimetric analysis (TGA) curve of n-
Fe3O4@TDI@TiO2 in the temperature range 30-800 °C. The
thermograph of the n-Fe3O4@TDI@TiO2 depicts two stages
decomposition. The first region is below 150 °C which attributed to
the loss of trapped water and solvents from the catalyst. The second
weight loss (12%) in the region between 150 and 455 °C can be
considered as the thermal decomposition of the TDI groups.29 On the
basis of these results, the well grafting of TDI is verified.
Figure 2. TGA curve of n-Fe3O4@TDI@TiO2.
2 | Catal. Sci. Technol., 2016, 00, 1-9
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Field emission scanning electron microscopy
TiO2 nanoparticles with anatase crystalline phase which matched
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Morphological studies of n-Fe3O4, n-TiO2 and n-Fe3O4@TDI@TiO2 with the standard XRD data of JCPD cardDnOuIm: 1b0e.1r03(98/9C-64C9Y2010)3a16nHd
were performed using FE-SEM micrographs as shown in Fig. 3. Fe3O4 according to Debaye-Scherrer’s equation, the average n-TiO2
and TiO2 nanoparticles have an approximate diameter of 20-50 and diameter for 2θ = 25.30˚ is calculated to be around 22 nm. For the
20-40 nm with nearly spherical shapes (Fig. 3a and b). After covalent XRD of n-Fe3O4@TDI@TiO2 (Fig. 4c), compared to n-Fe3O4 (Fig. 4a),
grafting of TDI and n-TiO2 on the surface of Fe3O4 nanoparticles, the the extra diffraction peaks matched well with those of anatase TiO2
resultant nanomaterials still have the morphology of spherical shape (Fig. 4b), which approves the modification of magnetic nanoparticles
with a larger particle size of 80-100 nm (Fig. 3c). These results with n-TiO2. Besides, from the XRD, crystallinity of Fe3O4 and TiO2
confirm the presence of the catalyst in nanometer-sized particles.
nanoparticles are well retained throughout the process.
Figure 4. The X-ray diffraction patterns of the (a) n-Fe3O4, (b) n-TiO2, (c) n-
Fe3O4@TDI@TiO2.
Vibrating sample magnetometer
Paramagnetic particles are highly valuable for their magnetic
separation; so, the magnetic properties of n-Fe3O4 and n-
Fe3O4@TDI@TiO2 were characterized by
a vibrating sample
magnetometer (VSM). According to the magnetization curves in Fig.
5, the saturation of the n-Fe3O4@TDI@TiO2 decreases to 30 emu/g
from 49 emu/g in the initial Fe3O4 sample due to the existence of
nonmagnetic materials on the surface of n-Fe3O4, which is still
sufficient for quickly magnetic separation with a conventional
magnet. Nonetheless, the reversibility in hysteresis loop confirms
that no aggregation occurs to the nanoparticles in the magnetic
fields. Moreover, according to curve c, the recycled catalyst after 6
runs showed very slight decrease (28 emu/g) in the magnetization
value which could be still easily separated from solution under an
external magnetic field.
Figure 3. FE-SEM images of (a) n-Fe3O4, (b) n-TiO2, (c) n-Fe3O4@TDI@TiO2.
X-ray diffraction spectra
The crystalline nature of n-Fe3O4@TDI@TiO2 is demonstrated by XRD
and along with X-ray diffraction patterns of Fe3O4 and TiO2
nanoparticles as shown in Fig. 4. In curve a, the peaks at the values
of 2θ equal to 30.4 (220), 35.7 (311), 43.4 (400), 54.1 (422), 57.1 (511)
and 62.9 (440) corresponds to cubic Fe3O4 structure which conforms
with the JCPD 79-0417 standard and the mean crystalline sizes of
Fe3O4 nanoparticles are calculated to be 14.5 nm using Debaye-
Scherrer’s equation, D=kλ/βcosθ, where k is a constant (generally
considered as 0.94), λ is the wavelength of Cu-Ka (1.54 ˚A), β is the
corrected diffraction line full-width at half-maximum (FWHM), and θ
is Bragg’s angle.30 As shown in curve b, the typical diffraction signals
located at 2θ equal to 25.2 (101), 37.3 (103), 37.8 (004), 38.7 (112),
48.2 (200), 54.0 (105), 55.1 (211), 62.8 (204), 68.9 (116), 70.4 (220),
75.1 (215) and 83.1 (224) can be well assigned to the diffraction of
Figure 5. Magnetization curves of the (a) n-Fe3O4, (b) n-Fe3O4@TDI@TiO2, (c) recycled
catalyst after 6 runs measured at room temperature.
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2.2. Evaluation of the catalytic activity of n-Fe3O4@TDI@TiO2
Tetrahydrobenzo[b]pyrans, as an important class of oxygen- shown in Table 2.
and six central points. The design layout and response values are
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DOI: 10.1039/C6CY00316H
containing heterocycles, are of considerable interest because of their
Table 2. Conditions of predicted experiments in CCD for three effective factors in
the synthesis of 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile.
useful pharmacological and biological properties. Furthermore, they
are versatile synthons that can be easily converted into pyridine
compounds as pharmacologically important calcium antagonists.31, 32
Due to the versatile utilization of the pyran derivatives in the field of
organic synthesis as well as in medicinal chemistry, we have
Run
1
2
3
4
5
6
7
8
X1
0
0
+1
0
-1
-1
+1
0
X2
0
+1.68
-1
0
-1
+1
+1
0
0
0
0
0
-1
-1
-1.68
0
+1
0
X3
0
0
+1
0
-1
-1
-1
0
Yield (%)
94.45
93.20
85.01
92.00
58.05
73.18
82.45
94.00
92.56
92.88
88.00
69.28
67.35
64.90
65.55
90.60
82.10
93.96
95.20
63.55
investigated catalytic activity of n-Fe3O4@TDI@TiO2 as
heterogeneous nanocatalyst for their synthesize (Scheme 2).
a
9
0
0
0
0
0
10
11
12
13
14
15
16
17
18
19
20
+1.68
0
+1
-1
0
0
+1
0
-1.68
-1
+1
0
+1.68
-1
0
Scheme 2. Synthesis of tetrahydrobenzo[b]pyrans using n-Fe3O4@TDI@TiO2 as
nanocatalyst.
For this purpose, the reaction of dimedone, benzaldehyde and
malononitrile as a model reaction was probed to establish the
feasibility of the strategy and optimize the reaction conditions. In
order to find the optimal conditions, the central composite design
(CCD), one of the most applicable types of response surface model
(RSM), was applied which offers benefits of attaining the same
amount of information while keeping the number of experimental
conditions minimal, without losing precision. It has been accepted as
an effective optimization method in attainment to improved
responses via a fitted quadratic model which can be expressed by
following equation:
+1
0
+1
0
+1
-1.68
The analysis of variance (ANOVA) performed on the model can
give valuable information on the significance of fitted model and
its terms. From the ANOVA, as shown in Table 3, p-values of model
and lack of fit are lower and higher than 0.05, respectively which
means fitted model is significant in confidence level of 95%.
Additionally, the results imply that all the independent variables (X1,
2
2
X2 and X3) and their quadratic terms (X1 , X22 and X3 ) significantly
affect the response value (yield), and a significant interaction
between catalyst amount (X1) and time (X3) is apparent (P<0.05).
Also, the amounts of R-squared and adj R-squared are above 0.9 and
close to each other, indicates fitted model has high accuracy and
reliability in prediction of the reaction yield. In other words, there is
a good agreement between experimental and the predicted
responses which confirms the suitability of the following model.
4
4
4
4
2
Y = β0 + ∑ βi Xi + ∑ ∑ βij XiXj + ∑ βii Xi
i=1
i=1 j=1
i=1
In which Y is response, Xi and Xj are independent variables, 훃ퟎ is
the constant model, 훃퐢, 훃퐢퐢 and 훃퐢퐣 are coefficients for the linear,
quadratic and interaction effects, respectively.
First, preliminary experiments were carried out to investigate the
appropriate parameters and to determine the experimental domain.
According to these experiments, the effects of catalyst amount (X1),
temperature (X2), and reaction time (X3) were performed on reaction
yield as response. A five-level CCD of three independent variables
with their corresponding values are shown in Table 1. Actual values
of each factor are represented in coded pattern.
Table 3. Analysis of variance for the response surface quadratic model for yield.
Sum of
Squares
3097.89
501.23
793.84
622.46
0.57
26.79
7.49
364.26
393.78
608.89
24.03
Mean
Square
F
p-value
Prob > F
< 0.0001
< 0.0001
< 0.0001
< 0.0001
0.6361
0.0075
0.1080
< 0.0001
< 0.0001
< 0.0001
Source
df
Value
Model
X1: Catalyst amount
X2: Temperature
X3: Time
9
1
1
1
1
1
1
1
1
1
10
5
5
344.21 143.21
501.23 208.54
793.84 330.29
622.46 258.98
0.57
26.79
7.49
364.26 151.55
393.78 163.84
608.89 253.34
2.40
3.87
0.93
X1X2
X1X3
0.24
11.15
3.12
Table 1. The experimental levels of variables in CCD for the synthesis of 2-amino-
7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile.
X2X3
2
Levels
X1
Independent
variables
2
X2
Lowest
(-1.68)
Low
(-1)
Central
(0)
High
(+1)
Highest
(+1.68)
2
X3
Residual
Lack of Fit
Pure Error
Cor Total
R2= 0.99
X1: Catalyst amount
(mg)
15
20
25
70
30
80
35
19.37
4.66
3121.93
4.16
0.0720
X2: Temperature (°C)
50
60
60
90
90
19
Adj-R2= 0.98
Pred-R2= 0.94
X3: Time (sec)
120
150
180
Based on the ANOVA results, the following equation was obtained:
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Based on CCD method, total number of experiments was found
to be 20 which consisted of eight full factorial points, six axial points
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Y
Yield = −502.97 + 10.18X1 + 8.60X2 + 1.88X3 − 5.35 × 10−3X1X2
+ 0.01X1X3 − 3.22 × 10−3X2X3 − 0.2X12 − 0.05X22
− 7.22 × 10−3X32
(
)
Eventually to making sure that the solvent free condition is
appropriate, the effect of different classical solvents such as EtOH,
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H2O, CH2Cl2, PhCH3 and polyethylene glycol-400 (PEG-400) has been
examined. Using these solvents, not only gave significantly lower
yields and longer reaction times, but also increasing the reaction
times did not improve the yields. So the best media was the solvent
free condition.
At the next step, the scope and generality of this protocol for
various aromatic aldehydes and cyclic 1,3-diketone compounds was
investigate under the optimized conditions (Table 4).
The coefficients of the equation show the effect of the
parameters. The more the value is, the more the effect is. So, it can
be realized from response equation that the X1 has the most linear
effect on the product yield, therefore the amount of catalyst can be
considered as the main factor in progressing the reaction.
In order to investigate the main interaction effects between two
parameters on the yield of reaction, three-dimensional profiles of
yield versus a pair of parameters were applied (Fig. 6). According to
their p-values, interaction of X1X3 is significant; it means that
simultaneous increment of the catalyst amount and time cause to
increase the product yield until 28 mg of the catalyst within 2 min.
Table 4. Synthesis of tetrahydrobenzo[b]pyran derivatives by n-Fe3O4@TDI@TiO2.
Melting point (°C)
Time
(min)
Yieldb
(%)
Entry
Ar
R1=R2
Found Reported
1
2
3
4
5
6
7
8
-C6H5
4-H3C-C6H4
4-H3CO-C6H4
4-HO-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
2-Cl-C6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
2
3
3
4
3
2
1
2
1
1
4
2
4
2
3
2
3
3
2
1
2
1
1
2
1
2
3
4
94
90
91
85
94
95
97
94
97
88
94
91
80
95
91
90
83
91
95
98
94
97
89
92
95
89
93
81
212-214 213-21533
232-234 234-23634
190-191 190-19233
233-234 234-23633
195-197 196-19833
200-201 201-20233
234-235 235-23734
212-213 212-21433
226-228 225-22734
229-232 235-23831
202-204 199-20033
171-173 171-17431
192-193 195-19831
228-230 229-23032
217-219 215-21735
199-200 196-19835
206-207 205-20633
224-225 224-22633
204-206 211-21233
174-176 174-17635
211-213 212-21335
211-213 208-21032
206-208 207-20832
9
4-Cl-C6H4
4-Br-C6H4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
2-Furfural
4-(CH3)2N-C6H4
C6H5-CH=CH-
-C6H5
4-H3C-C6H4
4-H3CO-C6H4
4-HO-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
2-Cl-C6H4
4-Cl-C6H4
4-Br-C6H4
4-F-C6H4
4-(CH3)2N-C6H4
2-Naphthyl
2-Furfural
C6H5-CH=CH-
Figure 6. Three-dimensional response surfaces for the effect of factors on the reaction
yield.
Based on the 30 experimental data, with the aid of desirability
function by using Design-Expert 7.0.0., the model predicted the
optimum yield for this reaction could reach 95.52%, with the optimal
process conditions of 28 mg catalyst, 70 °C reaction temperature
within 2 min (Fig. 7). In order to verify the adequacy of the model,
three parallel experiments were conducted, under the above
conditions and negligible difference between the average yields and
the prediction values of software was observed which meant that the
predicted and experimental data had a good agreement.
221-223
-
210-212 206-20831
229-231
-
205-206 201-20333
190-192 185-18831
a Reaction conditions: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), n-Fe3O4@TDI@TiO2 (0.028 g)
under solvent-free condition at 70 °C.
b Isolated yield.
Interestingly, a variety of 1,3-cyclic diketones and aryl aldehydes
bearing electron‐withdrawing or electron‐donating substituents
(ortho‐, meta‐, and para‐substituted) participated well in this
reaction and gave the product in good to excellent yield (80-98%)
within 1-4 min. Moreover, heteroaromatic aldehyde could also
successfully convert to its corresponding tetrahydrobenzo[b]pyran
product with excellent yield (Table 4, entries 11 and 24). The
formation and purity of products was confirmed by their melting
point determination which were in good accordance with the
literature values and the structures of some of the products were
well characterized by using FT-IR, 1H NMR and 13C NMR spectral data.
The plausible mechanism for the formation of
tetrahydrobenzo[b]pyrans is outlined in Scheme 3 which is consist of
three major stages: Knoevenagel condensation, Michael addition
and finally intramolecular ring closure.36 Due to Lewis acidity of the
Fe3O4 and TiO2 nanoparticles, n-Fe3O4@TDI@TiO2 acts as a catalyst
and activates methylene compound (I) and aldehyde (II) to facilitate
Figure 7. Optimized parameters resulted from the model.
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Catalysis Science & Technology
Table 5. Synthesis of hexahydroquinoline derivatives by n-Fe3O4@TDI@TiO2.
the formation of the Knoevenagel condensation product (III)
followed by a dehydration step (IV). Then, 1,3-cyclic dicarbonyl
compound (V) converts to its enole form after tautomerisation (VI)
and attack the electrophilic center of (IV) to form a carbon–carbon
bond via a Michael addition (VII) followed by tautomerism and
intramolecular O-cyclization (VIII). It is noteworthy to mention that,
during ring closure step, the catalyst plays the critical role in which it
can minimize the 1,2 dipolar repulsion between the geminal nitrile
groups and activates one of the nitriles by polarization (through
coordination). The latter is then tautomerization and proton transfer
which leads to the desired product (VIIII).
View Article Online
b
DOI: 10.M10e3lt9in/Cg6pCoYin0t0(3°C16)H
Time
(min)
Yield
(%)
Entry
Ar
R1=R2
Found
Reported
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
-C6H5
4-H3C-C6H4
4-H3CO-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
2-Cl-C6H4
4-Cl-C6H4
4-Br-C6H4
4-F-C6H4
H
H
H
H
H
H
H
H
H
20
22
25
30
15
15
18
20
19
18
20
25
27
20
15
17
14
17
18
15
35
40
90
88
85
87
90
90
91
93
92
95
92
89
88
90
93
89
91
90
90
94
85
82
257-258
260-261
277-279
228-230
240-242
259-260
286-288
287-289
250-252
286-287
278-279
290-293
289-291
231-234
284-285
293-295
271-273
291-293
295-298
297-298
>300
25737
25837
27837
-
24337
26037
28637
28937
-
H
28637
-C6H5
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
(1 mmol),
275-27738
294-29538
289-29338
-
4-H3C-C6H4
4-H3CO-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
2-Cl-C6H4
4-Cl-C6H4
4-Br-C6H4
4-F-C6H4
282-28339
290-29239
273-27638
290-29139
295-29639
299-30039
>30039
-
4-(CH3)2N-C6H4
2-Naphthyl
22
260-263
a
Reaction conditions:
1
2
(1 mmol),
3
(1 mmol),
6
(2.5 mmol), n-
Fe3O4@TDI@TiO2 (0.028 g) under solvent-free condition at 70 °C.
b Isolated yield.
As indicated in Table 5, the reaction works easily for a vast variety
of aromatic aldehydes with both electron-donating and electron-
withdrawing groups and different cyclic di-ketones, giving
corresponding hexahydroquinoline derivatives in good to excellent
yields which are in good accordance with melting points of literature
values. Moreover, the structures of some of the products were well
characterized by using FT-IR, 1H NMR and 13C NMR spectral data.
The suggested mechanism for the synthesis of
hexahydroquinolines is shown in Scheme 5. This mechanism is similar
to that of benzo[b]pyrans, but due to presence of ammonium
acetate, 1,3-cyclic dicarbonyl compound (V) condenses with NH4OAc
(VI) to give (VII) followed by removal of an acetic acid and in the
intramolecular ring closure step, nitrogen atom acts as a nucleophile
(VIII) and intramolecular N-cyclization occurs (IX) which leads to final
product (X).
Scheme 3. Possible mechanism for the synthesis of tetrahydrobenzo[b]pyrans in the
presence of n-Fe3O4@TDI@TiO2 as a nanocatalyst.
Encouraged by these results and in order to generalize the
catalytic efficiency of n-Fe3O4@TDI@TiO2, our study was followed by
the synthesis of hexahydroquinolines via
cyclocondensation reaction using cyclic
a
four-component
1,3-diketones,
benzaldehydes, malononitrile and ammonium acetate under the
optimized condition reaction of tetrahydrobenzo[b]pyrans (Scheme
4).
Scheme 4. Synthesis of hexahydroquinolines using n-Fe3O4@TDI@TiO2 as nanocatalyst.
Scheme 5. Suggested mechanism for the synthesis of hexahydroquinolines in the
presence of n-Fe3O4@TDI@TiO2 as a nanocatalyst.
6 | Catal. Sci. Technol., 2016, 00, 1-9
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ARTICLE
In order to compare the efficiency of the prepared Lewis acid
nanocatalyst with other reported Lewis acid nanocatalysts as well as
to exhibit the merit of the present work, our results are compared
View Article Online
DOI: 10.1039/C6CY00316H
with some other previously reported studies in the Table 6.
Table 6. Comparison of n-Fe3O4@TDI@TiO2 with some of the reported catalysts in the
synthesis of 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-
carbonitrile.
Time Yield
Entry
Catalyst
Reaction condition
Ref.
Figure 9. FE-SEM images of n-Fe3O4@TDI@TiO2 before use (a) and after reused six times
(b).
(min)
300
210
35
25
20
15
15
7
(%)
87
86
92
94
93
81
83
93
1
2
3
n-Pd
n-ZnO
n-TiO2
CH3CN/reflux
EtOH:H2O/r.t.
Solvent-free/70 °C
EtOH/r.t.
Solvent-free/95 °C
Solvent-free/100 °C
Grinding/r.t.
[35]
[36]
[40]
[41]
[32]
[32]
[42]
[31]
3. Experimental
Materials and instruments
n-SiO2
4
5
6
7
8
n-Fe3O4@SiO2@TiO2
n-Fe3O4
All chemicals were used without any further purification and
purchased from the Merck and Aldrich chemical companies. Toluene
diisocyanate (TDI) was in industrial grade with 80:20 mixture of 2,4
and 2,6 isomers and it was used as received. Solvents were purified
by conventional methods. The purity of products was checked by thin
layer chromatography (TLC) on glass plates coated with silica gel 60
F254 using n-hexane/ethyl acetate mixture as mobile phase. Melting
points were recorded on THERMO SCIENTIFIC 9100 apparatus.
Fourier transform infrared spectroscopy (FT-IR) were recorded on a
Shimadzu 8400 spectrometer in the range of 400–4000 cm−1 using
KBr pressed powder discs. Thermogravimetric analyses (TGA) were
conducted using a Du Pont 2000 thermal analysis apparatus heated
from 25°C to 800 °C at ramp 5°C/min under air atmosphere. Field
emission scanning electron microscope (FE-SEM) images were
acquired with a Philips XL30 field emission scanning electron
microscope (Royal Philips Electronics, Amsterdam, The Netherlands)
instrument operating at 25 kV. Particles were mounted on a double
sided adhesive carbon disk and sputter-coated with a thin layer of
gold to prevent sample charging problems. Wide-angle X-ray
diffraction (XRD) measurements were performed at room
temperature on a Siemens D5000 (Siemens AG, Munich, Germany)
using Cu-Ka radiation of wavelength 1.54 ˚A. The magnetite
measurement was carried out in a vibrating sample magnetometer
(VSM) (4 inch,Daghigh Meghnatis Kashan Co., Kashan, Iran) at room
temperature. 1H and 13CNMR spectra were recorded on Bruker
Advance Spectrometer 300 & 400 MHz and 75 & 100 MHz
respectively, in CDCl3-d and DMSO-d6 with tetramethylsilane (TMS)
as the internal reference.
n-PbO
n-CoFe2O4
EtOH:H2O/60 °C
This
work
9
n-Fe3O4@TDI@TiO2
Solvent-free/70 °C
2
95
It is evident from the Table 5 that, n-Fe3O4@TDI@TiO2 is highly
efficient in minimizing the reaction time and even in terms of product
yield, catalyst amount, elimination of solvent, easy separation and
recovery of the catalyst. These advantages can be attributed to the
highly activity due to nano porosity and high surface area of the
catalyst.
Recycling of the catalyst
From the industrial and large scale operations points of view,
reusability is the principal advantage for an efficient heterogeneous
catalyst. Hence, the reusability of the catalyst was scanned. Findings
revealed the same catalytic activity for the six times reused catalyst
as the fresh one, without any loss of the activity which means that
the catalyst structure is preserved (Fig. 8).
Preparation of the magnetic Fe3O4 nanoparticles
Magnetic Fe3O4 nanoparticles were prepared by co-precipitation of
Fe2+ and Fe3+ ions with NH4OH following the reported procedure.19
FeCl3·6H2O (5.838 g, 0.0216 mol) and FeCl2·4H2O (2.147 g, 0.0108
mol) were added to 100 mL deionized water at 80–85 °C under N2
atmosphere and vigorous stirring. Next, 10 mL of 25% aqueous
ammonia was quickly added into the reaction mixture in one portion
which resulted in immediate precipitation of MNPs. The reaction
continued for another 30 min and was cooled to room temperature.
The resulted black precipitate was separated by applying an external
magnet, washed five times with distilled water and dried in vacuum
at room temperature for 48 hr.
Figure 8. Reusability of n-Fe3O4@TDI@TiO2 for the synthesis of benzo[b]pyrans, Reaction
conditions: dimedone (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol) and n-
Fe3O4@TDI@TiO2 (28 mg); reaction time: 2 min at 70 °C under solvent free condition.
The identity of the recovered catalyst was checked by FE-SEM
which suggested that the nature of the catalyst remains intact and
there was no change in the morphology during the reaction and
recycling stages as compared to the fresh catalyst (Fig .9).
Functionalization of Fe3O4 nanoparticle with TDI (n-Fe3O4@TDI)
A mixture of 1.0 g Fe3O4 nanoparticle and 1.40 g TDI was dispersed
in 50 mL dried toluene and placed in an ultrasonic bath for 10-15 min.
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Then the reaction mixture was maintained at the temperature of 95
°C by a thermostat and stirred for 20 h under the atmosphere of
nitrogen. The powder product was magnetically separated and
carefully washed with dry toluene to remove the unreacted and
physical absorbed TDI. The product, was dried in vacuum at 100 °C
for 4 h.
Conclusions
View Article Online
Core shell and composites are routine approDaOchI:e1s0f.1o0r3m9/aCg6nCeYt0iz0a3t1i6oHn
of metal oxides. In our unique and powerful strategy, a novel method
for magnetization of metal oxides is presented through the usage of
TDI as linker due to the regioselectivity of two different isocyanate
groups. Moreover, this method could be extended to link other
different metal oxides too as well as the magnetic ones. So an
exclusive route for the synthesis of a heterogeneous nanocatalyst is
reported here through the action of the organic linker, toluene
diisocyanate, in which two metal oxide nanoparticles are linked to
together. Nano-Fe3O4@TDI@TiO2 was successfully synthesized and
applied for synthesize of tetrahydrobenzo[b]pyrans and
Preparation of TiO2 nanoparticles
The nano-TiO2 was synthesized by hydrothermal method according
to the previously reported procedure.23 Briefly, NH3.H2O was added
to TiCl4 solution until the pH value become 1.8. After stirring for 2 h
at 70 °C, the final pH of the solution was adjusted to 6. The resulting
suspension was aged at ambient temperature for 24 h. The final
product was filtered, washed with NH4Ac-HOAc until no Cl- was
detected. Then, the precipitate was separated using a centrifuge and
was washed with ethanol, dried in a vacuum. After 2 h treatment at
650 °C, TiO2 nanoparticles were obtained.
hexahydroquinolines by
a one-pot multicomponent reactions
strategy under solvent-free conditions. Short reaction times, high
yields of products, solvent-free with mild reaction conditions, easy
magnetically separability and reusability of the catalyst are the main
superiorities of this unique nanocatalyst.
Preparation of the n-Fe3O4@TDI@TiO2
1.0 g Fe3O4@TDI nanoparticles were dispersed in 100 mL dried
toluene. Subsequently, 0.3 g TiO2 nanoparticles were added into the
dispersion and heated at 110 °C under constant stirring for 24 h. The
product was magnetically separated, washed with acetone and then
dried at 100 °C for 4 h.
Acknowledgements
We gratefully acknowledge the Faculty of chemistry of Semnan
University for supporting this work.
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View Article Online
DOI: 10.1039/C6CY00316H
Graphical abstract
Nano-Fe3O4@TDI@TiO2 as a novel heterogeneous nanocatalyst is synthesized by covalent linkage of
n-Fe3O4 and n-TiO2 through the TDI.