Sulfamic acid-functionalized nano-titanium dioxide as an efficient, mild and highly recyclable solid acid nanocatalyst for chemoselective oxidation of sulfides and thiols

Article abstract of DOI:10.1039/c5ra20507g

A highly efficient and retrievable titanium dioxide-based nanocatalyst has been synthesized by covalent grafting of chlorosulfonic acid on amine-functionalized titania as a novel inorganic-organic hybrid heterogeneous nanocatalyst, which was characterized by Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The acid strength of the catalyst was determined by pH analysis and the Hammett acidity function. The potential of the resultant nanocatalyst was effectively evaluated for the chemoselective oxidation of sulfides to sulfoxides and thiols to disulfides using 30% H₂O₂ as an oxidant at room temperature under solvent-free conditions, which led to high conversion rates and yields. Optimization of the reaction conditions was studied by central composite design (CCD), which is one of the most widely used response surface methodologies. The catalyst can be easily recycled up to 10 times without significant decrease in catalytic activity, which makes it a promising catalyst for practical and large-scale applications. This work is the first report that uses 2,4-toluene diisocyanate as a linker for immobilizing liquid acid on a support.

Full text of DOI:10.1039/c5ra20507g

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Sulfamic acid-functionalized nano-titanium dioxide as an efficient,
mild and highly recyclable solid acid nanocatalyst for
chemoselective oxidation of sulfides and thiols
Received 00th January 20xx,
Accepted 00th January 20xx
Elham Tabrizian, Ali Amoozadeh* and Salman Rahmani
DOI: 10.1039/x0xx00000x
A highly efficient and retrievable titanium dioxide-based nanocatalyst has been synthesized by covalent grafting of
chlorosulfonic acid on the amine-functionalized titania as a novel inorganic–organic hybrid heterogeneous nanocatalyst,
which was characterized by Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy
(FE-SEM), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The acid strength of the catalyst was determined
by the pH analysis and Hammett acidity function. The potential of resultant nanocatalyst was effectively evaluated for the
chemoselective oxidation of sulfides to sulfoxides and thiols to disulfides using 30% H2O2 as an oxidant at room
temperature under solvent-free conditions which led to high conversion rates and yields. Optimization of the reaction
condition was studied by central composite design (CCD) which is one of the most widely used response surface
methodologies. The catalyst can be easily recycled up to 10 times without significant decrease in catalytic activity, which
makes it a promising catalyst for practical and large-scale applications. This work is the first report that uses 2,4-toluene
www.rsc.org/
diisocyanate
as
a
linker
for
immobilizing
liquid
acid
on
a
support.
materials so-called inorganic–organic hybrids and can improve their
ability to act in a variety of academic or technological activities. An
obvious advantage of such hybrids is the desirable combination of
both organic and inorganic properties in one nanomaterial.
1. Introduction
Homogeneous acid catalysts are widely used in a variety of organic
transformations, including hydrolyses, aldol condensations,
acylations, nucleophilic additions, etc. However, several drawbacks
such as highly corrosive and hazardous nature, separation
problems, reactor corrosion, waste neutralization and especially
inability to be reused are associated with the reactions catalyzed by
homogeneous liquid acids.1 Hence, overcoming the aforementioned
problems remains a challenge to chemists and is still strongly
desired. Following the successful immobilization of chlorosulfonic
acid on silica support which was reported by Zolfigol,2 avenues for
design and engineering of new and interesting solid acid catalysts
opens up and there is now a growing interest in the further
development of this type of catalysts.3-11 The use of solid
heterogeneous catalysts for the development of clean processes is
a theme of extreme importance in the chemical industries due to
better regio- and stereoselectivity, low toxicity, high stability, easy
separation, moisture resistance, air tolerance, easy handling and
reusability.12, 13
In this study, we have reported a novel strategy to immobilize
sulfonic acid groups on the surface of TiO2 nanoparticles, by
employing 2,4-toluene diisocyanate (TDI) as a covalently bound
linker. Compared with the expensive conventional coupling agents
(titanate and silane coupling agents) employed to organically
modify the surface of TiO2 nanoparticle, TDI is readily available, low-
cost, and very active due to its highly unsaturated bonds.
Furthermore, the reaction between TiO2 nanoparticle and TDI
occurs fast, easily and without any catalyst. To the best of our
knowledge, there are no literature reports on investigating the
usage of TDI as a linker in the catalyst modifications and catalytic
activity of TDI-based compounds. So we have decided to estimate
the catalytic applicability of the synthesized catalyst for the
oxidation of sulfides to sulfoxides and also oxidative coupling of
thiols into corresponding disulfides. Sulfoxides are fine chemicals,
pharmaceuticals and valuable intermediates in the synthesis of
16
chemically useful and biologically active molecules.15, Likewise,
The highest degree of evolution in the surface immobilization
strategy is the covalent attachment of an organic component to a
solid support.14 The combination of nanometer-sized inorganic
disulfides are essential moieties of biologically active compounds
and possess wide variety of chemical and industrial applications.17,
18
Concerning their importance, there has been a plethora of
moieties with organic compounds in
a single material has
research targeting these transformations under either catalyst-free
condition19 or in the presence of various catalysts,20-22 using
different oxidant.
extraordinary significance for development of multifunctional
2. Result and Discussion
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In extension of our ongoing programs on preparation of new the reaction of toluene diisocyanate with titania takes place
heterogeneous catalysts for organic reactions,23-26 we wish to through the formation of a urethane bond (OCONH)33 and the peak
report the preparation and application of sulfamic acid- at 1533 cm-1 is related to the phenyl ring of TDI. These results
functionalized nano-TiO2 as
a new, efficient and recyclable clearly confirmed that the TDI molecule was covalently linked to
nanocatalyst (Schemes 1). TDI is utilized to establish a bridge TiO2 nanoparticle. According to (Fig. 1d), by using water, the
between the surface of nano-titania and sulfonic acid to improve isocyanate peak at 2266 cm-1 is disappeared and converted to
the recyclability and lifetime of the inorganic–organic hybrid amine group which is overlapped with N-H bond of urethane bond
catalyst. Such a methodology provides a rigid covalent linkage at 3267 cm-1. Reaction of n-TiO2-NH2 with chlorosulfonic acid
between the support and sulfonic acid moiety.
produces n-TiO2-NHSO3H, in which the presence of sulfonyl moiety
is indicated by the absorptions in 1222 and 1159 cm−1 which are
certified the O=S=O asymmetric and symmetric stretching modes
lies respectively and the O-H stretch is appeared as a very broad
band from 2400 to 3400 cm-1 as can be seen in Fig. 1e.
N
C
O
O
C
H
N
Toluene diisocyanate
dry toluene, 95 °C, 6h
n-TiO2
n-TiO2
n-TiO2
n-TiO2
O
CH3
OH
N
C
O
NH2
CH3
H2O/Acetone
(5/5)
O
C
O
C
H
N
H
N
n-TiO2
O
CH3
O
30 °C, 2h
O
S
NH2
CH3
HN
OH
O
C
O
C
O
CH3
Chlorosulfonic acid
H
N
H
n-TiO2
O
O
N
dry CH2Cl2, rt, 30 min
Scheme 1. Preparation of sulfamic acid-functionalized n-TiO2 (n-TiO2-NHSO3H).
As illustrated in Scheme 1, at the first step, n-TiO2 was easily
synthesized by hydrothermal method according to the literature
report.27 Afterward, TiO2 nanoparticle surface was treated with TDI
and accessible surface hydroxyls of nano TiO2 preferentially reacted
with a para-isocyanate group of TDI to form urethane bond28, 29 and
left an ortho-isocyanate group unreacted due to the different
reactivity of the two isocyanate groups together with steric
hindrance in TDI molecule.30 At the next step, the unreacted
isocyanate group was converted to amine by treating it with water
and a new solid base is produced which could probably find unique
uses in various technical, industrial and organic applications. Finally,
the n-TiO2-NH2 nanoparticle was transformed to n-TiO2-NH-SO3H via
a
condensation reaction with chlorosulfonic acid. This novel
nanocatalyst was characterized via FT-IR, FE-SEM, XRD, TGA, acid-
Figure 1. FT-IR spectra of (a) nano-TiO2, (b) TDI, (c) n-TiO2-NCO, (d) n-TiO2-NH2 and (e)
base titration and Hammett acidity function method.
n-TiO2-NHSO3H.
2.1. Characterization of sulfamic acid-functionalized n-TiO2 (n-
TiO2-NHSO3H)
2.1.2. Field emission scanning electron microscopy
To study the surface morphology of nano-TiO2 and modified nano-
TiO2 nanostructures, SEM micrographs were employed. The
scanning electron microscopy (SEM) (Fig. 2a) and transmission
electron microscopy (TEM) (Fig. 2b) analysis of nano TiO2 powder
indicates the spherical shape with average size of 20–30 nm. The
SEM micrographs of the n-TiO2-NH2 (Fig. 2c) and n-TiO2-NHSO3H
(Fig. 2d) show an enlargement in particles diameter sizes to about
50–80 nm and 90-140 nm respectively. In n-TiO2-NHSO3H,
aggregation of n-TiO2 nanoparticles is clearly seen.
2.1.1. FT-IR spectra
In order to evaluate successful conjugation of sulfamic acid onto the
surface of the nano-TiO2, FT-IR spectra of the nano-TiO2 and every
step of the reaction was analyzed. As shown in Fig. 1a, the broad
intense band below 1200 cm−1 is attributed to Ti-O-Ti vibration and
the absorbance at 1623 and 3355 cm−1 are assigned to the surface
31
hydroxyl groups of TiO2. Curve b 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,32 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-TiO2 (Fig. 1c), compared with the spectrum of the
pristine TiO2 nanoparticle (Fig. 1a), is revealed additional peaks at
2266, 1649, 1595, and 1533 cm-1. The peak at 2266 cm-1 can be
attributed to the unreacted ortho-isocyanate groups of TDI
attached to the n-TiO2 surface, while the bands at 1649 and 1595
cm-1 can be assigned to the C=O and C-N stretches indicating that
2 | J. Name., 2012, 00, 1-3
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wt.%) below 100 °C due to the loss of the physically adsorbed water
and then had a slight weight loss (1 wt.%) between 100 °C and 800
°C, which could be ascribed to the dehydroxylation of n-TiO2
according to literatures.35 The thermograph of the n-TiO2-NHSO3H
depicts three stages decomposition. The first region is below 100 °C
which is attributed to the loss of trapped water from the catalyst.
The second weight loss (11%) in the region between 225 and 308 °C
correlates quite well with that for TDI-modified titania which is in
good agreement with data reported by other authors.36 The third
step at curve b (T>314 °C) is attributed to either TDI or mainly to the
decomposition of the grafted SO3H groups. On the basis of these
results, the well grafting of TDI and sulfonic acid groups on the n-
TiO2 is verified.
Figure 2. FE-SEM image of n-TiO2 (a), TEM image of n-TiO2 (b), FE-SEM image of n-TiO2-
NH2 (c), FE-SEM image of n-TiO2-NHSO3H (d).
2.1.3. X-ray diffraction spectra
X-ray diffraction measurement was performed to investigate the
influence of modifications on the surface of nano support. As
shown in Fig. 3a, the typical diffraction signals located at (101),
(103), (004), (112), (200), (105), (211), (204), (220), (215) and (224)
can be well assigned to the diffraction of TiO2 nanoparticles with
anatase crystallite phase which matched with the standard XRD
data of JCPD card number (89-4921). The average n-TiO2 diameter
for 2θ = 25.303˚ was calculated to be around 22 nm from the XRD
results by 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.34 According to Fig. 3, the
position and relative intensities of all peaks in the XRD pattern of n-
TiO2-NH2 and n-TiO2-NHSO3H confirm well with XRD pattern of
nano-TiO2, indicating retention of the anatase crystallite phase
structure during functionalization of nano-TiO2 (Fig. 3b).
Figure 4. TGA curves of (a) nano-TiO2, (b) n-TiO2-NHSO3H.
2.1.5. pH analysis of catalyst
To determine the Brönsted acid amount on the surface of catalyst,
the prepared catalyst (100 mg) was ion-exchanged with 10 mL of 1
M NaCl solution at room temperature by sonication, followed by
filtration and washing with 5 mL deionized water. Then, the filtrate
was titrated with NaOH (0.01 M) solution in the presence of pH
meter. The required volume of NaOH to reach equivalence point
was 10 ml which is equal to a loading of 1 mmol/g of sulfamic acid
group.
2.1.6. Surface acidity studies
The acidity of solid samples is commonly reported as a function of
Hammett acidity (H0).37 Using this method, the solid samples are
placed in the presence of indicator dyes with known pKa values
(mainly substituted nitroanilines), wherein the indicator trapped
the dissociated proton of the catalyst. Then, UV-visible
spectrometer is used to determine the concentrations of
protonated and unprotonated indicator molecules exactly
according to the Lambert-Beer law.
Figure 3. The X-ray diffraction patterns of the (a) nano-TiO2, (b) n-TiO2-NH2, (c) n-TiO2-
The Hammett acidity function could be calculated with the
following equation:
NHSO3H.
2.1.4. Thermo gravimetric analysis
H0= pK(I)aq + log([I]s/[IH+]s)
One indication of bond formation between the nanoparticles and
the catalyst can be inferred from thermogravimetric analysis (TGA).
Fig. 4 shows thermogravimetric analysis (TGA) curves of nano-TiO2
and n-TiO2-NHSO3H in the temperature range 30 °C-800 °C. The
results of Fig. 4a indicate that nano-TiO2 showed a weight change (4
Where, ‘I’ displays the indicator base (here 4-nitroaniline) and [IH+]s
and [I]s are the molar concentrations of the protonated and
unprotonated forms of indicator respectively. The pK(I)aq is the
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O
S
protonation constant of the dye in aqueous solution (for example
the pK(I)aq value of 4-nitroaniline is 0.99).
n-TiO2-NHSO3H, H2O2
Solvent-free, rt
S
R1
R2
R1
R2
In this experiment, 4-nitroaniline was selected as the basic
indicator, and CCl4 was chosen as the solvent due to its aprotic
property. First, a dilute solution (10–4 M) of 4-nitroaniline in CCl4
Scheme 2. Nano-TiO2-NHSO3H catalyzed oxidation of sulfides to sulfoxides using H2O2.
was prepared and used as
a stock solution. The maximum
For this purpose, the reaction of methyl phenyl sulfide and
hydrogen peroxide 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. 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:
absorbance for the unprotonated indicator in UV-vis spectra we
observed at 331 nm as shown in Fig.5. Then, 20 mg of the catalyst
was added to the solution and mixed for 30 min with magnetic
stirring, and the UV spectrum of the solution was recorded. By
adding catalyst, the absorbance of the unprotonated form of the
indicator decreased to 1.276 due to trapping the acidic protons.
ꢃ
ꢃ
ꢃ
ꢃ
ꢇ
Y = βꢀ + ꢁ βꢂ Xꢂ + ꢁ ꢁ βꢂꢆ XꢂXꢆ + ꢁ βꢂꢂ Xꢂ
ꢂꢄꢅ
ꢂꢄꢅ ꢆꢄꢅ
ꢂꢄꢅ
In which Y is response, Xi and Xj are independent variables, ꢈꢉ is the
constant model, ꢈꢊ, ꢈꢊꢊ and ꢈꢊꢋ are coefficients for the linear,
quadratic and interaction effects, respectively.
First of all, preliminary experiments were carried out to
investigate the appropriate parameters and to determine the
experimental domain. Considering these experiments, the effects of
catalyst amount (X1), H2O2 concentration (X2), and reaction time (X3)
were performed on reaction yield as response. A five-level CCD of
three independent variables with their corresponding values is
shown in Table 2.
Figure 5. Absorption spectra of (a) 4-nitroaniline (indicator), (b) nano-TiO2-NHSO3H
(catalyst) and (c) recovered catalyst after ten runs in CCl4.
The difference in the measured absorbance is used to
determine the acid strength of the catalyst (Table 1).
Table 2. The experimental levels of variables in CCD for the synthesis of methyl
phenyl sulfoxide.
Levels
Table 1. Hammett acidity function (H0) data for n-TiO2-NHSO3H.
Independent
Lowest
(-1.68)
Low
(-1)
Central
(0)
High
(+1)
Highest
(+1.68)
[IH+]s (%)
0
H0
-
variables
Entry
Catalyst
Amax
[I]s (%)
100
X1: Catalyst
amount (mg)
1
2
-
2.410
1.276
6.64
8
10
12
13.36
n-TiO2-NHSO3H
64.79
35.21
1.44
X2: H2O2 (equiv.)
X3: Time (min)
1.13
6.59
1.4
10
1.8
15
2.2
20
2.47
Recovered after
ten runs
3
1.359
69.44
30.56
1.50
23.40
Condition for UV-visible spectrum measurement: solvent, CCl4; indicator, 4-nitroaniline
(pK(I)aq= 0.99), 1.44*10-4 mol/L; catalyst, n-TiO2-NHSO3H (20 mg), 25 °C.
Based on CCD method, total number of experiments was found
to be 20 which consisted of eight full factorial points, six axial points
and six central points. Conditions of 20 trials companied to their
respective yields are shown in Table 3.
The results of Table 1 approves that the SO3H groups were
successfully tethered on the support (Table 1, entry 2) and catalyst
leaching is partial and acidic groups are well grafted on TDI (Table 1,
entry 3).
Table 3. Conditions of predicted experiments in CCD for three effective factors in
the synthesis of methyl phenyl sulfoxide.
2.2. Evaluation of catalytic activity of n-TiO2-NHSO3H for the
oxidation of sulfides to sulfoxides
Run
1
2
3
4
5
6
7
8
X1
-1
0
X2
-1
0
0
0
0
0
0
-1
+1
0
0
+1
X3
+1
0
0
0
Yield (%)
47.76
90.43
92.88
79.9
92.76
90.16
91.72
31.06
78.55
92.88
62.12
59.23
The selective oxidation of sulfides to sulfoxides is a fundamental
and important functional group transformation in organic synthesis
because organic sulfoxides are useful building blocks in the
construction of pharmaceuticals, agrochemicals, and other valuable
fine chemicals and in drug metabolisms.38-40 Therefore, we
investigated catalytic activity of n-TiO2-NHSO3H as a heterogeneous
nanocatalyst for the chemoselective oxidation of structurally
diverse sulfides to sulfoxides using 30% H2O2 as an oxidant (Scheme
2).
0
+1.68
0
0
0
0
0
+1.68
-1
-1
-1
+1
0
0
-1
9
10
11
12
0
-1.68
-1
4 | J. Name., 2012, 00, 1-3
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13
14
15
16
17
18
19
20
+1
-1
0
-1.68
+1
0
+1
0
-1
+1
-1.68
0
+1
+1.68
-1
-1
+1
0
0
+1
0
61.66
81.68
49.44
41.51
93.59
96.15
74.49
90.86
Residual
Lack of Fit
Pure Error
Cor Total
45.52
36.93
8.59
10
4.55
7.39
1.72
5
5
4.30
0.0677
7868.33
Adj-R2=
0.98
19
Pred-R2=
R2= 0.99
0.96
+1
0
0
Y = ꢌ617.31 + 72.77Xꢅ + 229.18Xꢇ + 9.20Xꢍ ꢌ 4.08XꢅXꢇ
ꢌ 2.88Xꢅꢇ ꢌ 45.42Xꢇꢇ ꢌ 0.23Xꢍꢇ
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 4, p-values of
model and lack of fit are lower and higher than 0.05, respectively
which means that, fitted model is significant in confidence level of
95% and it does not require to reduce to lower orders. Also, the
amounts of R-squared and adj R-squared are above 0.9 and close to
each other which indicates fitted model has high accuracy and
reliability in prediction of the reaction yield. In other words, there is
It can be realized from response equation that the X2 and X1
have a linear effect on the product yield, so the amount of H2O2 and
the catalyst can be considered as the main factors in progressing of
the reaction.
In order to investigate the main interaction effects between
two parameters on the yield of reaction, three and two-dimensional
profiles of yield versus a pair of parameters were applied (Fig. 6).
According to their p-values, interaction of X1X2 is significant; it
means that simultaneous increment of the catalyst amount and
H2O2 concentration cause to increase the product yield until 10 mg
of the catalyst and 2 equivalent of H2O2.
a
good agreement between experimental and the predicted
responses which confirms the suitability of the following fitted
model in terms of significantly linear, quadratic and interaction
terms on the basis of their p-values.
The main goal of this design was to optimize and maximize the
yield of the reaction corresponded to the conditions of an
experiment in which the response equation was maximized. In this
work, determination of optimal conditions was done with the aid of
desirability function by using Design-Expert 7.0.0. It was firstly
selected desired goals for each factor and for response to obtain
the maximum product yield with high desirability function (close to
one). Then, conditions possessing high desirability were tested
three times. Negligible difference between the average yields and
the prediction values of software, confirms the high accuracy and
precision of optimum conditions. The results showed that 10 mg of
the catalyst, 2 equivalent of H2O2, and 15 min reaction time were
the optimum conditions for the synthesis of methyl phenyl
sulfoxide.
Table 4. The results of ANOVA in CCD for the synthesis of methyl phenyl
sulfoxide.
Sum of
Squares
7822.81
Mean
Square
869.20
F
p-value
Prob > F
< 0.0001
Source
df
9
Value
190.93
Model
X1: Catalyst
amount
X2: H2O2
X3: Time
X1X2
1716.86
1
1716.86
377.13
< 0.0001
2284.60
998.95
85.15
1
1
1
1
1
1
1
1
2284.60
998.95
85.15
501.84
219.43
18.70
3.49
< 0.0001
< 0.0001
0.0015
X1X3
15.90
15.90
0.0911
X2X3
7.92
7.92
1.74
0.2166
2
X1
1919.99
761.26
486.40
1919.99
761.26
486.40
421.75
167.22
106.84
< 0.0001
< 0.0001
< 0.0001
2
X2
2
X3
Figure 6. Three and two dimensional response surfaces for the effect of factors on the reaction yield.
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To compare the efficiency of the solvent-free versus solvent
ARTICLE
These results prompted us to investigate the scope and
conditions, the model reaction was performed under optimum generality of this protocol for various sulfides (aliphatic and
condition in the presence of EtOH, H2O, CH3CN and phCH3. The aromatic) under the optimized conditions.
results showed that higher yield and shorter reaction time were
obtained when the reaction was carried out under solvent-free
condition.
Table 5. Oxidation of sulfides to sulfoxides in the presence of nano-TiO2-NHSO3Ha.
Time
(min)
Yieldb
(%)
Selectivity
(%)
Entry
1
Sulfide
Sulfoxide
23
15
10
13
8
92
90
98
95
98
100
100
100
100
100
2
3
4
5
6
7
15
25
98
93
100
100
8
9
10
10
97
97
100
100
10
30
85
100
11
12
25
60
95
80
100
100
13
10
95
100
14
30
65
93
100
100
15c
90d
a Reaction condition: Sulfide (1 mmol), n-TiO2-NHSO3H (10 mg), H2O2 (2 eq.), solvent-free, at room temperature.
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b Isolated Yields.
c The starting material was prepared according to ref. no. 41
d Tow diastereoisomers were separated.
.
Time
(min)
5
Yieldb
(%)
97
As shown in Table 5, a variety of sulfides such as dialkyl sulfides
(Table 5, entries 1-5), alkyl aryl sulfides (Table 5, entries 6-9), and
other sulfides with different functional groups (Table 5, entries 10-
15) could be smoothly converted to corresponding sulfoxides with
high conversion rate and excellent selectivity and no overoxidation
products such as sulfones were detected in the reaction mixtures.
Moreover, the influence of steric effects could be observed in this
catalytic system. For example, the oxidation of diphenyl sulfide
required much longer reaction time in comparison to isopropyl
phenyl sulfide and its product yield was much lower too (Table 5,
entries 9 and 12). The structures of some of the products were well
characterized by using 1H NMR spectral data.
Entry
Thiol
Disulfide
1
2
10
98
3
4
7
95
15
15
97
93
5
There are two proposed mechanisms for the oxidation of
sulfides using hydrogen peroxide in the presence of an acidic
catalyst which are depicted in Scheme 3.42 One explanation for this
process is the in-situ formation of peroxyacid by the reaction of
catalyst with hydrogen peroxide, followed by the oxygen transfer to
the organic substrate (Scheme 3a). Another explanation is that
catalyst might act as a protic acid that acid interaction or hydrogen
bonding of sulfonic acid with hydrogen peroxide polarizes the O-O
bond in H2O2 to produce the reactive oxygen transfer agent.43 At
the same time, the deporting of water as a leaving group would be
assisted by nucleophilic attack of sulfide (Scheme 3b).
6
7
17
90
20
25
90
89
8
a
Reaction condition: Thiols (1 mmol), n-TiO2-NHSO3H (10 mg), H2O2 (2 eq.), solvent-
free, at room temperature.
b Isolated Yields.
The generality of this approach has been demonstrated in Table
6. As shown, a variety of thiols bearing aliphatic thiols (Table 6,
entries 1 and 2), aromatic thiols (Table 6, entries 3-6), and other
thiols with different functional groups were successfully employed
to prepare the corresponding disulfides in short reaction time and
excellent yields. Moreover, in all the reactions no any byproducts
was observed.
The suggested mechanism for the oxidative coupling of thiols is
illustrated in Scheme 5.22 Combination of hydrogen peroxide with
catalyst would generate OH radical which would subsequently react
with thiol to produce thiol radical, followed by dimerization to
afford corresponding disulfide.
Scheme 3. Proposed mechanisms for the oxidation of sulfides using H2O2 catalyzed by
O
n-TiO2-NHSO3H.
HN
S
OH
O
C
O
CH3
H
N
n-TiO2
O
The chemoselectivity of the reaction may be controlled by
hydrogen bonding, since the hydrogen bonds between the acidic
catalyst and the oxygen of the sulfoxides could decrease the
nucleophilicity of the sulfur atom in the sulfoxides and prevent
overoxidation of the sulfoxide to a sulfone.44
HOH
H2O2
Encouraged by these results and in order to generalize the
catalytic efficiency of n-TiO2-NHSO3H, our study was followed by the
oxidative coupling of thiols into their corresponding disulfides
under the optimized condition reaction of sulfoxides (Scheme 4).
R3-SH
R3-S
O
C
H
N
n-TiO2
R3-SH
O
CH3
O
HN
S
O
O
H
S
S
O
R3
R3
R3-SH
Scheme 5. Proposed mechanism for the oxidative coupling of thiols using H2O2
catalyzed by n-TiO2-NHSO3H.
Scheme 4. Nano-TiO2-NHSO3H catalyzed oxidative coupling of thiols to disulfides using
H2O2.
2.3. Recycling and leaching of the catalyst
Table 6. Oxidative coupling of thiols into disulfides in the presence of nano-TiO2-
NHSO3Ha.
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Reusability is one of the important criteria for an efficient
heterogeneous catalyst in organic transformations and makes them
useful for commercial applications. The synthesized catalyst is
capable to run the oxidation reaction after 10 runs efficiently
and all reactions were led to the desired product without significant
changes in terms of the reaction time and yield which clearly
demonstrates practical recyclability of n-TiO2-NHSO3H (Fig. 7). In
addition, the weight of the recovered catalyst was the same as that
of the fresh catalyst used for the first time in the reaction.
Figure 9. FE-SEM images of n-TiO2-NHSO3H before use (a) and after reused ten times
(b).
Additionally, the FT-IR spectrum of the catalyst after ten cycles
are identical to the corresponding spectrum before catalytic
reaction which confirmed the existence of acidic groups on the
surface of catalyst (Fig. 10).
Figure 7. Reusability of n-TiO2-NHSO3H for the synthesis of methyl phenyl sulfoxide;
Reaction conditions: methyl phenyl sulfide (1 mmol), H2O2 (2 eq.), catalyst (10 mg),
reaction time: 15 min at room temperature under solvent-free condition.
Conversion as a function of reaction time for the recycling of n-
TiO2-NHSO3H is illustrated in Figure 8. As can be seen from the
kinetic curves, initial rates for the ten successive recycling runs are
similar and reaction rates are nearly constant and no further
significant loss of activity is detected.
Figure 10. FT-IR spectra of n-TiO2-NHSO3H before use (a) and after reused ten times (b).
To explore the catalyst leaching in the oxidation of ethyl phenyl
sulfide, the reaction was stopped at half the reaction time (5 min)
and the solid catalyst was completely separated from the solution
by centrifuge. Then, the solution was kept back for oxidation under
the same conditions. As can be seen in Fig. 11, no appreciable
progress and increase in the product yield was observed, even after
20 min (monitored by TLC). These results confirm that the reaction
is attributed to the heterogeneous catalyst and catalyst leaching is
negligible.
Figure 8. Plot of conversion vs. reaction time for the recycled n-TiO2-NHSO3H in the
synthesis of methyl phenyl sulfoxide; Reaction conditions: methyl phenyl sulfide (1
mmol), H2O2 (2 eq.), catalyst (10 mg), reaction time: 15 min at room temperature 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).
Figure 11. Leaching experiment; Reaction conditions: ethyl phenyl sulfide (1 mmol),
H2O2 (2 eq.), catalyst (10 mg), at room temperature under solvent-free condition.
3. Experimental
3.1. Materials and instruments
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All chemicals were used without any further purification and 3.5. Preparation of sulfamic acid-functionalized n-TiO2 (n-TiO2-
purchased from the Merck and Aldrich chemical companies. NHSO3H)
Toluene diisocyanate (TDI) was in industrial grade with 80:20 Nano-TiO2-NH2 was modified using a suction flask equipped with a
mixture of 2,4 and 2,6 isomers and it was used as received. Solvents constant pressure dropping funnel containing 0.25 ml
were purified by conventional methods. The purity of products was chlorosulfonic acid (3.75 mmol) and a gas inlet tube for conducting
checked by thin layer chromatography (TLC) on commercial plates HCl gas over an adsorbing solution such as water. The flask was
coated with silica gel 60 F254 using n-hexane/ethyl acetate mixture charged with 1.0
g n-TiO2-NH2 in 10 ml dry CH2Cl2 and
as mobile phase. Melting points were recorded on THERMO chlorosulfonic acid was then added drop wisely over a period of 30
SCIENTIFIC 9100 apparatus. Fourier transform infrared spectroscopy min at room temperature. Upon completion of the addition, the
(FT-IR) were recorded on a Shimadzu 8400 spectrometer in the mixture was stirred for a further 1 h to allow for the complete
range of 400–4000 cm−1 using KBr pressed powder discs. Field dissipation of HCl from the reaction vessel. Then, the CH2Cl2 was
emission scanning electron microscope (FE-SEM) images were removed under reduced pressure and the solid powder was washed
acquired with a Philips XL30 field emission scanning electron twice with ethanol (10 mL) and dried at 70 °C for 4 h.
microscope (Royal Philips Electronics, Amsterdam, The Netherlands)
3.6. General procedure for the catalytic oxidation of sulfides
instrument operating at 25 kV. Particles were mounted on a double
To a mixture of the sulfide (1 mmol) and 30% H2O2 (2 eq), the
sided adhesive carbon disk and sputter-coated with a thin layer of
catalyst (10 mg) was added and the mixture was stirred at room
gold to prevent sample charging problems. Wide-angle X-ray
temperature for a specified time. The progress of the reaction was
diffraction (XRD) measurements were performed at room
monitored by TLC (n-hexane/EtOAc, 9/1). After completion of the
temperature on a Siemens D5000 (Siemens AG, Munich, Germany)
reaction, the reaction mixture was eluted with Et2O (10 mL) and
using Cu-Ka radiation of wavelength 1.54 ˚A. Thermogravimetric
centrifuged to filter the catalyst. The combined organic layers were
analyses (TGA) were conducted using a Du Pont 2000 thermal
dried over anhydrous Na2SO4 and evaporation of diethyl ether
analysis apparatus heated from 25°C to 800 °C at ramp 5°C/min
under reduced pressure gave the pure products in 80–98% yields.
under air atmosphere. The NMR spectra were measured in pure
deuterated chloroform with a Bruker Advance 400 MHz instruments
3.7. General procedure for the catalytic oxidative coupling of
(1H NMR 400 MHz) with tetramethylsilane (TMS) as the internal
thiols
reference. The absorption spectra in the UV-visible regions were
To a mixture of thiol (1 mmol) and 30% H2O2 (2 eq), the catalyst (10
recorded by a UV-1650 PC-UV–Vis spectrophotometer (Shimadzu,
mg) was added and the mixture was stirred at room temperature
Japan).
for a specified time. The progress of the reaction was monitored by
TLC (n-hexane/EtOAc, 8/2). After completion of the reaction, the
3.2. Preparation of nano-TiO2
reaction mixture was eluted with CH2Cl2 (10 mL) and centrifuged to
The nano-TiO2 was synthesized by hydrothermal method according
filter the catalyst. The combined organic layers were dried over
to the previously reported procedure.27 Briefly, NH3.H2O was added
anhydrous Na2SO4 and evaporation of CH2Cl2 under reduced
to TiCl4 solution until the pH value become 1.8. After stirring for 2 h
pressure gave the pure products in high yields.
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.
3.8. General procedure for recycling of n-TiO2-NHSO3H
In order to investigate the recoverability and recyclability of
catalyst, the oxidation of methyl phenyl sulfide (1 mmol) under the
optimized conditions was chosen as model reaction. Upon
completion of the reaction, the catalyst was separated via
centrifuge, washed with ether (2 × 5 mL) and acetone (2 × 5 mL)
dried at 70 °C for 1 h to be used in the next cycles.
3.3. Functionalization of TiO2 nanoparticle with TDI (n-TiO2-NCO)
The n-TiO2-NCO was prepared following the reported procedure.36
A mixture of 1.0 g TiO2 nanoparticle and 1.40 g TDI was dispersed in
50 ml dried toluene and placed in an ultrasonic bath for 10-15 min.
Then the reaction mixture was maintained at the temperature of 95
°C by a thermostat and stirred for 6 h under the atmosphere of
nitrogen. The powder product was separated by centrifugation and
then carefully washed with dry toluene to remove the unreacted
and physical absorbed TDI. The product, was dried in vacuum at 80
°C for 24 h.
Conclusions
In conclusion, for the first time, we described here a new class of
inorganic–organic hybrid nanocatalyst based on toluene 2,4-
toluene diisocyanate as a linker for potential synthetic application.
This efficient and environmentally friendly Brönsted acidic catalyst
was used successfully for the chemoselective oxidation of sulfides
and thiols. Operational simplicity, low cost and non-toxic nature,
excellent chemoselectivity, applicability to large-scale reactions,
high yields of products, and high recyclability are the main
superiorities of our new catalyst, which make it as a promising
catalyst for technical, industrial and organic applications. Studies
toward further applications of this catalyst for other organic
transformations and also exploring the powerful potential of using
3.4. Preparation of amine-functionalized n-TiO2 (n-TiO2-NH2)
A round bottom flask of 100 mL capacity was charged with 1.0 g (n-
TiO2-TDI) and 50 ml of H2O–acetone mixture at mass ratio of 5/5.
The flask was immersed in a water bath at 30 °C, under stirring. The
reaction was allowed to continue for 2 h, followed by centrifugation
to separate the solid, which was rinsed twice by acetone and dried
at 110 °C under vacuum to get a powder product.
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Acknowledgements
We gratefully acknowledge the Faculty of chemistry of Semnan
University for supporting this work.
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Graphical Abstract
Sulfamic acid-functionalized nano-titanium dioxide as an efficient, mild and highly
recyclable solid acid nanocatalyst for chemoselective oxidation of sulfides and thiols
Elham Tabrizian, Ali Amoozadeh* and Salman Rahmani
Department of Organic Chemistry, Faculty of Chemistry, Semnan University, Semnan 35131-19111, Iran