pH-dependence of the aqueous phase room temperature Br?nsted acid-catalyzed chemoselective oxidation of sulfides with H2O2

Article abstract of DOI:10.3390/molecules200916709

A pH-dependence of the Br?nsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides with H2O2 is reported for the first time based on our systematic investigation of the catalytic performance of a series of Br?nsted acids. For all of the Br?nsted acids investigated, the catalytic performances do not depend on the catalyst loading (mol ratio of Br?nsted acid to substrate), but rather depend on the pH value of the aqueous reaction solution. All of them can give more than 98% conversion and selectivity in their aqueous solution at pH 1.30, no matter how much the catalyst loading is and what the Br?nsted acid is. This pH-dependence principle is a very novel perspective to understand the Br?nsted-acid catalysis system compared with our common understanding of the subject.

Full text of DOI:10.3390/molecules200916709

Molecules 2015, 20, 16709-16722; doi:10.3390/molecules200916709
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
pH-Dependence of the Aqueous Phase Room Temperature
Brønsted Acid-Catalyzed Chemoselective Oxidation of Sulfides
with H2O2
Hai-Min Shen 1,*, Wen-Jie Zhou 1, Xin Ma 1, Hong-Ke Wu 1, Wu-Bin Yu 1, Ning Ai 1,
Hong-Bing Ji 2, Hong-Xin Shi 1 and Yuan-Bin She 1,*
1
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China;
E-Mails: zhouwj0716@163.com (W.-J.Z.); shm190726@hotmail.com (X.M.);
wuhongke@zjut.edu.cn (H.-K.W.); yuwb@zjut.edu.cn (W.-B.Y.); aining@zjut.edu.cn (N.A.);
shihxin@zjut.edu.cn (H.-X.S.)
2
School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275,
China; E-Mail: jihb@mail.sysu.edu.cn
†
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed; E-Mails: haimshen@zjut.edu.cn (H.-M.S.);
sheyb@zjut.edu.cn (Y.-B.S.); Tel./Fax: +86-0571-8832-0533 (H.-M.S. & Y.-B.S.).
Academic Editor: Roman Dembinski
Received: 13 July 2015 / Accepted: 2 September 2015 / Published: 14 September 2015
Abstract: A pH-dependence of the Brønsted acid-catalyzed oxidation of sulfides to the
corresponding sulfoxides with H2O2 is reported for the first time based on our systematic
investigation of the catalytic performance of a series of Brønsted acids. For all of the
Brønsted acids investigated, the catalytic performances do not depend on the catalyst loading
(mol ratio of Brønsted acid to substrate), but rather depend on the pH value of the aqueous
reaction solution. All of them can give more than 98% conversion and selectivity in their
aqueous solution at pH 1.30, no matter how much the catalyst loading is and what the
Brønsted acid is. This pH-dependence principle is a very novel perspective to understand the
Brønsted-acid catalysis system compared with our common understanding of the subject.
Keywords: sulfide; oxidation; sulfoxide; pH-dependence; Brønsted acid

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1. Introduction
The chemoselective oxidation of sulfides to the corresponding sulfoxides is a very important
transformation in organic synthesis, since the obtained sulfoxides are important intermediates or
building blocks in the construction of pharmaceuticals, agrochemicals, and other valuable fine
chemicals [1–7]. To realize this extremely useful transformation, several oxidants can be employed, such
as hydrogen peroxide [8–13], molecular oxygen [14–19], tert-butyl hydroperoxide [20–23], cumene
hydroperoxide [24–27], iodobenzene diacetate [28–30], sodium hypochlorite [31–33], and oxone [34].
Among these oxidants, aqueous hydrogen peroxide is a very promising reagent compared to others, as
it is readily available, inexpensive, easy to handle, can be safely stored, and it is environmentally benign
with harmless water being the only by product generated in the reaction [9,35,36]. However, the
oxidation of sulfides to sulfoxides employing aqueous hydrogen peroxide in the absence of catalyst is a very
slow process, especially at room temperature. Thus, in order to accelerate this chemical transformation,
several catalytic systems have been developed such as transition metal complexes catalysis [37–41],
Brønsted-acid catalysis [35,42–45], organocatalyst catalysis [10,46–55], metal and metal oxide nanoparticles
catalysis [56–58], heteropoly acid catalysis [13,59–61], and the heterogenization of the above catalytic
systems [36,58,62–66]. Considering the high cost of the metal catalysts, inevitable metal residue
contamination of the products, and the toxicity of the transition metal complexes, Brønsted acids and
organocatalysts seem to be the more attractive choices, as well as for the high catalytic activity and
selectivity seen in Brønsted acids and organocatalysts catalysis.
Several Brønsted acids have been employed in the Brønsted-acid catalysis system to catalyze the
chemoselective oxidation of sulfides to corresponding sulfoxides, such as sulfuric acid (H2SO4) [62],
hydrochloric acid (HCl) [62], nitric acid (HNO3) [67], boric acid (H3BO3) [35], chiral phosphoric
acid [68], acetic acid (CH3COOH) [45], oxalic acid (HOOCCOOH) [44], p-toluenesulfonic acid
(H3CC6H4SO3H) [69], sulfamic acid (H2NSO3H) [43], dodecyl hydrogen sulfate [42], immobilized
sulfuric acid [62], immobilized phosphoric acid [70], immobilized sulfamic acid [36], and immobilized
vanadic acid [71].Excellent catalytic activity and chemoselectivity, and even enantioselectivity, could
usually be obtained in the above catalysis systems by optimizing the catalyst loading (mol ratio of
Brønsted acid to substrate). Although so many Brønsted-acid catalysis systems have been successfully
introduced in the chemoselective oxidation of sulfides to corresponding sulfoxides, a common feature of all
these different Brønsted-acid catalysis systems is that by far they have not been investigated systematically.
In our screening of modifying groups for β-cyclodextrin to construct artificial enzymes [72–74],
especially sulfide-oxidase, we found that the conversion, yield and chemoselectivity in the Brønsted
acid-catalyzed oxidation of sulfides seemed to be dependent on the catalyst loading, which meant that
different Brønsted acids could exhibit their optimal catalytic activity by optimizing its catalyst loading for
most cases, but in fact they depended on the concentration of the Brønsted acid in the aqueous phase, no
matter how much the catalyst loading was. These findings inspired us to try to explore some commonness
in the Brønsted acid-catalyzed oxidation of sulfides with H2O2, and finally a pH-dependence principle
was obtained. In this paper, we disclose the pH-dependence principle of the Brønsted acid-catalyzed
chemoselective oxidation of sulfides with H2O2 based on our systematic investigation of the catalytic
performance of a series of Brønsted acids, in which the conversion, yield and chemoselectivity depended
only on the pH of the aqueous reaction solution, no matter how much the catalyst loading is and what

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the Brønsted acid is. To the best of our knowledge, our study reveals a commonness in the Brønsted
acid-catalyzed oxidation of sulfides with H2O2 for the first time, so these attempts to explore the
commonness in the different Brønsted acid-catalyzed chemoselective oxidation of sulfides with H2O2
will not only provide a summary of the abundant previous studies, but also an important reference for
further studies of the Brønsted acid-catalyzed oxidation of sulfides, and even other Brønsted-acid
catalysis systems.
2. Results and Discussion
Camphor-10-sulfonic acid derived from the natural product camphor was the first Brønsted acid
investigated in our research. In order to optimize the reaction conditions, we chose the catalytic oxidation
of methyl phenyl sulfide as a probe reaction and systematically evaluated the effect of catalyst loading
on the probe reaction. As shown in Table 1, with the increase of catalyst loading from 0.0% to 25.0%,
the conversion and yield of the probe reaction increased from 34.1% to 99.2% and 34.1% to 98.3%
respectively, and meanwhile the chemoselectivity remained above 99.0% in cases. It seems that the
conversion and yield of the probe reaction depend heavily on the catalyst loading, but when we increased
the amount of substrate methyl phenyl sulfide from 1.0 mmol to 10.0 mmol and kept the other reaction
conditions as the same as Entry 11 in Table 1, which meant that the catalyst loading decreased from 25.0%
to 2.5%, surprisingly, the conversion and yield of the probe reaction almost did not decrease as expected,
and the conversion, yield and selectivity remained at the same level, as shown in Supplementary
Materials Table S1. When we decreased the amount of methyl phenyl sulfide substrate from 1.0 mmol to
0.40 mmol and kept the other reaction conditions as the same as Entry 2 in Table 1, which meant that the
catalyst loading increased from 2.5% to 6.25%, the conversion and yield of the probe reaction did not
increase as expected either, as shown in Supplementary Materials Table S2. These findings inspired us
to consider that in the Brønsted acid-catalyzed chemoselective oxidation of sulfides to the corresponding
sulfoxides, the conversion and yield might not depend on the catalyst loading, but rather on the concentration
of Brønsted acid in the aqueous phase.
In order to verify the generality of our findings, the scope of Brønsted acids were extended from
camphor-10-sulfonic acid to methanesulfonic acid, p-toluenesulfonic acid, methanoic acid and acetic acid.
The experimental data is presented in the Supplementary Materials. It is very clear that the relationships
between conversion and yield to catalyst loading in these typical Brønsted-acid catalysis systems are as
the same as with camphor-10-sulfonic acid. The conversion and yield seem to be dependent on the
catalyst loading, but in fact depend on the concentration of Brønsted acid in the aqueous phase. It was
also obtained from the experimental data that, to achieve their optimal catalytic performances, catalyst
concentrations may be different for different Brønsted acids. In our research, the amount of solvent was
fixed at 2.0 mL, but to achieve their optimized catalytic performances, the amounts of Brønsted acid
needed were 0.25, 0.25, 0.25, 4.00 and 5.50 mmol for camphor-10-sulfonic acid, methanesulfonic acid,
p-toluenesulfonic acid, methanoic acid and acetic acid, respectively, as shown in Table 2. Thus, it could
be concluded that in the Brønsted acid-catalyzed chemoselective oxidation of sulfides to the corresponding
sulfoxides, the catalytic performance depended on the concentration of Brønsted acid in the aqueous phase,
and different Brønsted acid exhibited optimized catalytic performance at different catalyst concentrations.

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Table 1. Effect of catalyst loading on the oxidation of methyl phenyl sulfide with H2O2
catalyzed by camphor-10-sulfonic acid a.
Entry Catalyst Loading (%) Conversion (%) b Yield (%) b
1
2
0.0
2.5
34.1
41.6
51.8
56.2
59.5
64.4
79.4
84.5
93.4
97.6
99.2
34.1
41.5
51.5
56.0
59.2
64.0
78.8
83.9
92.7
96.8
98.3
3
5.0
4
7.5
5
10.0
12.5
15.0
17.5
20.0
22.5
25.0
6
7
8
9
10
11
a Reaction conditions: substrate (1.0 mmol, 124.2 mg), 30% H2O2 (1.15 mmol, 130 µL), solvent (2.0 mL H2O),
25 °C, 24.0 h; b Conversion and selectivity were determined by GC with p-xylene as internal standard, product
was determined by comparison with the authentic sample.
Table 2. Optimized amount of Brønsted acid-catalysts in the oxidation of methyl phenyl
sulfide with H2O2 a and the pH value of the aqueous reaction solution.
Entry
Brønsted Acid
Amount (mmol) pH Value b Conversion (%) c Yield (%) c
1
0.25
1.28
99.6
99.3
2
3
0.25
0.25
1.25
1.30
99.7
99.7
98.8
98.8
4
5
4.00
5.50
1.31
1.35
99.1
99.1
98.6
98.9
a Reaction conditions: substrate (1.0 mmol, 124.2 mg), 30% H2O2 (1.15 mmol, 130 µL), solvent (2.0 mL H2O),
25 °C, 24.0 h; b pH of the solutions were measured independently without substrate and oxidant; c Conversion
and selectivity were determined by GC with p-xylene as internal standard, product was determined by
comparison with the authentic sample.
In order to further confirm this commonness in the Brønsted acid-catalyzed oxidation of sulfides to
the corresponding sulfoxides, some shared features in the aqueous solution reactions in Table 2 must be
explored. As a quantitative index for the aqueous solution of Brønsted acid, the pH values of the aqueous
reaction solutions in Table 2 were measured by a pH meter and are shown in Table 2. To our surprise

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they were similar, so we speculate that the common feature in the different Brønsted acid-catalyzed
chemoselective oxidations of sulfides might be the same pH level, no matter what the Brønsted acid is.
To verify our speculation, several typical Brønsted acids, such as camphor-10-sulfonic acid,
methanesulfonic acid, p-toluenesulfonic acid, methanoic acid, sulfuric acid, hydrochloric acid,
trifluoroacetic acid and boric acid were selected to prepare aqueous solutions with a series of pH values,
and their catalytic performance in the probe reaction were investigated systematically. As shown in Table 3,
in the aqueous solution of camphor-10-sulfonic acid, when the pH value decreased from 2.00 to 1.30,
the conversion and yield of the probe reaction increased from 42.6% to 99.6% and 42.6% to 98.9%,
respectively, and the chemoselectivity stayed at around 99.0%.
Table 3. Effect of pH value on the oxidation of methyl phenyl sulfide with H2O2 catalyzed
by camphor-10-sulfonic acid a.
Entry pH Value b Conversion (%) c Yield (%) c
1
2
2.00
1.90
1.80
1.70
1.60
1.50
1.40
1.30
1.20
1.10
1.00
42.6
49.5
58.1
66.9
72.1
77.9
98.1
99.6
99.8
99.6
99.4
42.6
49.2
57.9
66.4
71.4
77.1
96.3
98.9
98.6
97.2
96.5
3
4
5
6
7
8
9
10
11
a Reaction conditions: substrate (1.0 mmol, 124.2 mg), 30% H2O2 (1.15 mmol, 130 µL), catalyst and solvent
(2.0 mL aqueous solution of camphor-10-sulfonic acid), 25 °C, 24.0 h; b pH of the solutions were measured
c
independently without substrate and oxidant; Conversion and selectivity were determined by GC with
p-xylene as internal standard, product was determined by comparison with the authentic sample.
A further decrease in the pH value led to no increase in all of the conversion, yield and selectivity,
but rather a slight decrease. Similar catalytic performance profiles with pH of the aqueous solution
reaction were obtained for all of the Brønsted-acid catalysis systems employed herein. The experimental
data is presented in the Supplementary Materials. All of them exhibited their optimized catalytic
performance when the pH value of the aqueous reaction solution was 1.30. When we increased the
amount of methyl phenyl sulfide from 1.0 to 10.0 mmol, and the other reaction conditions were kept as
the same as Entry 8 in Table 3, all of the conversions, yield and selectivity stayed at the same level as
expected, without any decrease, as shown in Supplementary Materials Table S3. Thus, it is very obvious
that in the Brønsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides, pH-dependence
is a common feature, and no matter which Brønsted acids are used, they can all achieve their optimal
catalytic performance in their aqueous solution of pH 1.30, and the catalytic performance is not dependent

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on the catalyst loading which is a very novel perspective to understand the Brønsted-acid catalysis
system compared with our common knowledge of this process.
In order to verify the generality of the pH-dependence principle, both the scope of Brønsted acids and
sulfides were extended. It is clear from Table 4 that, for all of the typical Brønsted acids investigated,
satisfactory conversion, yield and selectivity could be obtained in their aqueous reaction solution of pH
1.30, and the conversion, yield and selectivity fluctuate in a very small range, being nearly constant.
Table 4. Oxidation of methyl phenyl sulfide with H2O2 catalyzed by Brønsted acids at
pH 1.30 a,b.
Entry
Brønsted Acid
Conversion (%) c Yield (%) c
1
99.6
98.9
2
3
99.8
99.7
98.7
98.5
4
98.7
97.9
5
6
7
99.6
99.2
99.7
99.1
98.6
98.3
8
99.8
98.5
9
98.8
99.6
99.7
99.5
99.6
97.7
99.1
98.8
98.9
98.7
10
11
12
13
14
99.6
98.8
15
99.7
98.5
a Reaction conditions: substrate (1.0 mmol, 124.2 mg), 30% H2O2 (1.15 mmol, 130 µL), catalyst and solvent
b
(2.0 mL pH 1.30 aqueous solution of Brønsted acid), 25 °C, 24.0 h; pH of the solutions were measured
c
independently without substrate and oxidant; Conversion and selectivity were determined by GC with
p-xylene as internal standard, product was determined by comparison with the authentic sample.
When the scope of sulfides was extended to a series of structurally diverse sulfides, a good substrate
tolerance was observed when employing camphor-10-sulfonic acid as a typical Brønsted acid catalyst in
pH 1.30 aqueous solution. As shown in Table 5, most of the sulfides could be oxidized to the corresponding
sulfoxides in more than 98% conversion and selectivity, especially for some liquid sulfides because of
their excellent dispersion in water. As for sulfides with poor water solubility, a mixture of H2O and CH3CN

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in the volume ratio of 1:1 was employed as solvent to enhance the substrate dispersion, and satisfactory
catalytic performance was achieved too.
Table 5. Oxidation of various sulfides to sulfoxides with 30% H2O2 catalyzed by
camphor-10-sulfonic acid in pH 1.30 a,b.
Entry
Sulfide
Conversion (%) c Yield (%) c
1
99.6
98.9
2
3
98.7
97.9
99.9
99.4
4
99.4
98.5
98.1
98.7
98.8
97.6
97.4
98.2
5 d
6 d
7 d
S
CH3
S
CH3
CH3
8
9
99.5
99.9
99.1
99.4
10 d
98.7
97.9
11 d
96.8
99.2
95.6
98.6
12
a Reaction conditions: substrate (1.0 mmol), 30% H2O2 (1.15 mmol, 130 µL), catalyst and solvent (2.0 mL pH
b
1.30 aqueous solution of camphor-10-sulfonic acid), 25 °C, 24.0 h; pH of the solutions were measured
c
independently without substrate and oxidant; Conversion and selectivity were determined by GC or HPLC
with p-xylene as internal standard, product was determined by comparison with the authentic sample
1
synthesized following the literature procedure [75] and characterized by H-NMR, 13C-NMR and ESI-MS;
d H2O and CH3CN in the volume ratio of 1:1 as solvent.
3. Experimental Section
3.1. General Information
13
1H-NMR and C-NMR spectra were measured on a AVANCE III NMR spectrometer (Bruker,
Fällanden, Switzerland) at 400 MHz in CDCl3. Tetramethylsilane was used as the internal standard

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(0.00 ppm) in CDCl3. The ESI-MS spectra were measured on an Agilent 6210 TOF LC/MS mass
spectrometer (Agilent Technologies, Palo Alto, CA, USA). GC analyses were performed on a GC-14B
instrument (Shimadzu, Kyoto, Japan) using a SPB-5 column (0.25 mm × 30 m). HPLC analyses were
performed on a Waters 1525 chromatograph (Waters, Milford, MA, USA) equipped with a Waters 2996
Photodiode Array Detector using a Hypersil ODS2-5 column (4.6 mm × 250 mm). All the catalytic
reaction were carried out in the Wattecs parallel synthesis system (Wattecs, Xi’an, China).
3.2. Materials
Sulfides used were purchased from Shanghai Energy Chemical Co. Ltd. (Shanghai, China), Aladdin
Chemistry Co. Ltd. (Shanghai, China), TCI Co. Ltd. (Tokyo, Japan), Aldrich Co. Ltd. (Shanghai, China),
or synthesized from thiophenol and corresponding alkyl bromide. Methyl phenyl sulfoxide was
purchased from Aldrich Co. Ltd. (Shanghai, China). Other sulfoxides were synthesized following the
literature procedure [75] and characterized by 1H-NMR, 13C-NMR and ESI-MS. Camphor-10-sulfonic
acid, methanesulfonic acid, p-toluenesulfonic acid, methanoic acid, sulfuric acid, hydrochloric acid,
trifluoroacetic acid, boric acid, taurine (2-aminoethanesulfonic acid), homotaurine (3-aminopropanesulfonic
acid) were purchased from Shanghai Energy Chemical Co. Ltd., Aladdin Chemistry Co. Ltd., and TCI Co.
Ltd. 30% H2O2 were purchased from Shanghai Lingfeng Chemical Reagent Co. Ltd. (Shanghai, China),
All the other common reagents were of an analytical grade. All of the reagents were used as received
without further purification unless otherwise noted.
3.3. General Procedure for Oxidation of Sulfides Catalyzed by Brønsted Acid (1)
Sulfide (1.0 mmol) was added to a solution of Brønsted acid in water (2.0 mL) in corresponding
amount, after stirring at 25 °C for 15 min, 30% H2O2 (1.15 mmol) was added. Then, the resultant mixture
was kept stirring at 25 °C for 24.0 h. At the end of the reaction, saturated aqueous Na2SO3 (2.0 mL) was
added to stop deep oxidation. The obtained solution was extracted with ethyl acetate (3 × 2.0 mL), and
the combined organic phase was washed with brine (2.0 mL) and dried over anhydrous Na2SO4. The
obtained solution was analyzed by GC or HPLC to determine the conversion and yield with p-xylene as
internal standard.
3.4. General Procedure for Oxidation of Sulfides Catalyzed by Brønsted Acid (2)
Sulfide (1.0 mmol) was added to a aqueous solution of Brønsted acid in certain pH (2.0 mL), after
stirring at 25 °C for 15 min, 30% H2O2 (1.15 mmol) was added. Then, the resultant mixture was kept
stirring at 25 °C for 24.0 h. At the end of the reaction, saturated aqueous Na2SO3 (2.0 mL) was added to
stop deep oxidation. The obtained solution was extracted with ethyl acetate (3 × 2.0 mL), and the combined
organic phase was washed with brine (2.0 mL) and dried over anhydrous Na2SO4. The obtained solution
was analyzed by GC or HPLC to determine the conversion and yield with p-xylene as internal standard.
4. Conclusions
In conclusion, a pH-dependence principle in Brønsted acid-catalyzed chemoselective oxidation of
sulfides to the corresponding sulfoxides with H2O2 is reported for the first time. For all the Brønsted

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acids investigated, their catalytic performances depend on the pH value of the aqueous solution reaction,
and do not depend on the Brønsted acid loading (mol ratio of Brønsted acid to substrate). All of the
Brønsted acids investigated can give more than 98% conversion and selectivity in their aqueous solution
of pH 1.30 with an excellent substrate tolerance, no matter what the Brønsted acids are. To the best of
our knowledge, this pH-dependence principle is the first common feature reported in the Brønsted
acid-catalyzed chemoselective oxidation of sulfides and represents a very novel perspective to understand
the Brønsted-acid catalysis system compared with our common understanding of these reactions. Thus,
our finding will be an important reference not only to further studies of Brønsted acid-catalyzed
oxidations of sulfides, but also to other Brønsted-acid catalysis systems. Further investigation on the
catalytic mechanism and attempts to apply the pH-dependence principle to other Brønsted acid-catalyzed
systems are under way.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/09/16709/s1.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Grant No. 21306176,
21276006, 21476270), Scientific Research Launching Foundation of Zhejiang University of Technology
(Grant No. G2817101103) and Zhejiang Provincial Natural Science Foundation (Grant No. LQ14B020002).
Author Contributions
Hai-Min Shen, Yuan-Bin She and Hong-Xin Shi contributed to the conception of the study, design
of the experiments, and writing of the paper. Wen-Jie Zhou, Xin Ma and Hong-Ke Wu contributed to
the catalysis experiments. Wu-Bin Yu, Ning Ai and Hong-Bing Ji contributed to the analysis of the
experimental data.
Conflicts of Interest
The authors declare no conflict of interest.
References
1. Fernandez, I.; Khiar, N. Recent developments in the synthesis and utilization of chiral sulfoxides.
Chem. Rev. 2003, 103, 3651–3705.
2. Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P. Oxidation of sulfides to sulfoxides. Part 2:
Oxidation by hydrogen peroxide. Tetrahedron 2005, 61, 8315–8327.
3. Stingl, K.A.; Tsogoeva, S.B. Recent advances in sulfoxidation reactions: A metal-free approach.
Tetrahedron:Asymmetry 2010, 21, 1055–1074.
4. Drabowicz, J.; Kielbasiński, P.; Zajac, A.; Wach-Panfilow, P. Synthesis of sulfides, sulfoxides and
sulfones. In Comprehensive Organic Synthesis, 2nd ed.; Molander, G.A., Knochel, P., Eds.; Elsevier:
Amsterdam, The Netherlands, 2014; Volume 6, pp. 131–174.

Molecules 2015, 20
16718
5. Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. Synthesis of sulfoxides. In Syntheses of Sulphones,
Sulphoxides and Cyclic Sulphides; Patai, S., Rappoport, Z., Eds.; Wiley: West Sussex, UK, 1994;
Volume 3, pp. 109–254.
6. Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. Synthesis of sulfoxides. In Syntheses of Sulphones,
Sulphoxides and Cyclic Sulphides; Patai, S., Rappoport, Z., Eds.; Wiley: West Sussex, UK, 1994;
Volume 4, pp. 255–388.
7. Drabowicz, J.; Mikolajczyk, M. Synthesis of sulfoxides. A review. Org. Prep. Proced. Int. 1982,
14, 45–89.
8. Le Maux, P.; Simonneaux, G. First enantioselective iron-porphyrin-catalyzed sulfide oxidation with
aqueous hydrogen peroxide. Chem. Commun. 2011, 47, 6957–6959.
9. Islam, S.M.; Roy, A.S.; Mondal, P.; Tuhina, K.; Mobarak, M.; Mondal, J. Selective oxidation of sulfides
and oxidative bromination of organic substrates catalyzed by polymer anchored Cu(II) complex.
Tetrahedron Lett. 2012, 53, 127–131.
10. Secci, F.; Frongia, A.; Piras, P.P. Ammonium salt catalyzed oxidation of organosulfides to
organosulfoxydes. Tetrahedron Lett. 2014, 55, 603–605.
11. Gogoi, P.; Kalita, M.; Bhattacharjee, T.; Barman, P. Copper-Schiff base complex catalyzed oxidation
of sulfides with hydrogen peroxide. Tetrahedron Lett. 2014, 55, 1028–1030.
12. Kon, Y.; Yokoi, T.; Yoshioka, M.; Tanaka, S.; Uesaka, Y.; Mochizuki, T.; Sato, K.; Tatsumi, T. Selective
hydrogen peroxide oxidation of sulfides to sulfoxides or sulfones with MWW-type titanosilicate
zeolite catalyst under organic solvent-free conditions. Tetrahedron 2014, 70, 7584–7592.
13. Huang, L.; Wang, S.S.; Zhao, J.W.; Cheng, L.; Yang, G.Y. Synergistic combination of multi-ZrIVcations
and lacunary keggin germanotungstates leading to a gigantic Zr24-cluster-substituted polyoxometalate.
J. Am. Chem. Soc. 2014, 136, 7637–7642.
14. Mirkhani, V.; Moghadam, M.; Tangestaninejad, S.; Mohammdpoor-Baltork, I.; Kargar, H.;Araghi, M.
Highly efficient oxidation of sulfides with sodium periodate catalyzed by reusable silica supported
Mn(Br8TPP)Cl and Mn(TPP)Cl catalysts under various reaction conditions. Appl. Catal. A Gen.
2009, 353, 61–67.
15. Rezaeifard, A.; Jafarpour, M. The catalytic efficiency of Fe-porphyrins supported on multi-walled
carbon nanotubes in the heterogeneous oxidation of hydrocarbons and sulfides in water. Catal. Sci. Tech.
2014, 4, 1960–1969.
16. Hu, Y.L.; Fang, D.; Xing, R. Efficient and convenient oxidation of sulfides to sulfoxides with molecular
oxygen catalyzed by Mn(OAc)2 in ionic liquid [C12mim][NO3]. RSC Adv. 2014, 4, 51140–51145.
17. Wang, Z.J.; Ghasimi, S.; Landfester, K.; Zhang, K.A.I. Highly porous conjugated polymers for selective
oxidation of organic sulfides under visible light. Chem. Commun. 2014, 50, 8177–8180.
18. Johnson, J.A.; Zhang, X.; Reeson, T.C.; Chen, Y.S.; Zhang, J. Facile Control of the charge density
and photocatalytic activity of an anionic indium porphyrin framework via in situ metalation. J. Am.
Chem. Soc. 2014, 136, 15881–15884.
19. Li, T.T.; Li, F.M.; Zhao, W.L.; Tian, Y.H.; Chen, Y.; Cai, R.; Fu, W.F. Highly efficient and selective
photocatalytic oxidation of sulfide by a chromophore-catalyst dyad of ruthenium-based complexes.
Inorg. Chem. 2015, 54, 183–191.
20. Das, R.; Chakraborty, D. Cu(II)-catalyzed oxidation of sulfides. Tetrahedron Lett. 2010, 51, 6255–6258.

Molecules 2015, 20
16719
21. Oble, J.; Riflade, B.; Noel, A.; Malacria, M.; Thorimbert, S.; Hasenknopf, B.; Lacote, E.
Carbonyl-inserted organo-hybrids of a dawson-type phosphovanadotungstate: Scope and chemoselective
oxidation catalysis. Org. Lett. 2011, 13, 5990–5993.
22. Rezaeifard, A.; Farshid, P.; Jafarpour, M.; Moghaddam, G.K. Silica-coated magnetite nanoparticles
stabilized simple Mn-tetraphenylporphyrin for aqueous phase catalytic oxidations with tert-butyl
hydroperoxide. RSC Adv. 2014, 4, 9189–9196.
23. Orive, J.; Larrea, E.S.; de Luis, R.F.; Iglesias, M.; Mesa, J.L.; Rojo, T.; Arriortua, M.I. Amine
templated open-framework vanadium(III) phosphites with catalytic properties. Dalton Trans. 2013,
42, 4500–4512.
24. Gao, J.H.; Guo, H.C.; Liu, S.Z.; Wang, M. Efficient soluble polymer-supported tartrate/Ti catalyst
for asymmetric oxidation of prochiral sulfides. Tetrahedron Lett. 2007, 48, 8453–8455.
25. Pordea, A.; Creus, M.; Panek, J.; Duboc, C.; Mathis, D.; Novic, M.; Ward, T.R. Artificial metalloenzyme
for enantioselective sulfoxidation based on vanadyl-loaded streptavidin. J. Am. Chem. Soc. 2008,
130, 8085–8088.
26. Mba, M.; Prins, L.J.; Zonta, C.; Cametti, M.; Valkonen, A.; Rissanen, K.; Licini, G. Ti(IV)-amino
triphenolate complexes as effective catalysts for sulfoxidation. Dalton Trans. 2010, 39, 7384–7392.
27. Romanowski, G. Synthesis, characterization and catalytic activity in the oxidation of sulfides and
styrene of vanadium(V) complexes with tridentate Schiff base ligands. J. Mol. Catal. A Chem. 2013,
368, 137–144.
28. Jaccob, M.; Comba, P.; Maurer, M.; Vadivelu, P.; Venuvanalingam, P. A combined experimental and
computational study on the sulfoxidation by high-valent iron bispidine complexes. Dalton Trans.
2011, 40, 11276–11281.
29. Chen, T.H.; Yuan, Z.B.; Carver, A.; Zhang, R. Visible light-promoted selective oxidation of sulfides
to sulfoxides catalyzed by ruthenium porphyrins with iodobenzene diacetate. Appl. Catal. A Gen.
2014, 478, 275–282.
30. Yu, B.; Guo, C.X.; Zhong, C.L.; Diao, Z.F.; He, L.N. Metal-free chemoselective oxidation of
sulfides by in situ generated Koser’s reagent in aqueous media. Tetrahedron Lett. 2014, 55, 1818–1821.
31. Khurana, J.M.; Nand, B. Aqueous sodium hypochlorite mediated chemoselective oxidation of
chalcogenides to monoxides and dioxides by microwave exposure. Can. J. Chem. 2010, 88, 906–909.
32. Huang, J.Y.; Li, S.J.; Wang, Y.G. TEMPO-linked metalloporphyrins as efficient catalysts for selective
oxidation of alcohols and sulfides. Tetrahedron Lett. 2006, 47, 5637–5640.
33. Alcon, M.J.; Corma, A.; Iglesias, M.; Sanchez, F. Homogeneous and encapsulated within the cavities
of zeolite Y chiral manganese and copper complexes with C2-multidentate ligands as catalysts for
the selective oxidation of sulphides to sulfoxides or sulfones. J. Mol. Catal. A Chem. 2002, 178,
253–266.
34. Yu, B.; Liu, A.H.; He, L.N.; Li, B.; Diao, Z.F.; Li, Y.N. Catalyst-free approach for solvent-dependent
selective oxidation of organic sulfides with oxone. Green Chem. 2012, 14, 957–962.
35. Rostami, A.; Akradi, J. Ahighly efficient, green, rapid, and chemoselective oxidation of sulfides using
hydrogen peroxide and boric acid as the catalyst under solvent-free conditions. Tetrahedron Lett. 2010,
51, 3501–3503.

Molecules 2015, 20
16720
36. Rostami, A.; Tahmasbi, B.; Abedi, F.; Shokri, Z. Magnetic nanoparticle immobilized N-propylsulfamic
acid: The chemoselective, efficient, green and reusable nanocatalyst for oxidation of sulfides to
sulfoxides using H2O2 under solvent-free conditions. J. Mol. Catal. A Chem. 2013, 378, 200–205.
37. Jeong, Y.C.; Huang, Y.D.; Choi, S.; Ahn, K.H. Synthesis of sterically controlled chiral
beta-amino alcohols and their application to the catalytic asymmetric sulfoxidation of sulfides.
Tetrahedron: Asymmetry 2005, 16, 3497–3501.
38. Aydin, A.E. Synthesis of novel beta-amino alcohols and their application in the catalytic asymmetric
sulfoxidation of sulfides. Tetrahedron: Asymmetry 2013, 24, 444–448.
39. Romanowski, G.; Lis, T. Chiral oxidovanadium(V) complexes with tridentate Schiff bases
derived from S-(+)-2-amino-1-propanol: Synthesis, structure, characterization and catalytic activity.
Inorg. Chim. Acta 2013, 394, 627–634.
40. Adao, P.; Avecilla, F.; Bonchio, M.; Carraro, M.; Pessoa, J.C.; Correia, I. Titanium(IV)-salan catalysts
for asymmetric sulfoxidation with hydrogen peroxide. Eur. J. Inorg. Chem. 2010, 2010, 5568–5578.
41. Nigel-Etinger, I.; Mahammed, A.; Gross, Z. Covalent versus non-covalent (biocatalytic) approaches
for enantioselective sulfoxidation catalyzed by corrole metal complexes. Catal. Sci. Tech. 2011, 1,
578–581.
42. Firouzabadi, H.; Iranpoor, N.; Jafari, A.A.; Riazymontazer, E. Metal-free chemoselective oxidation
of sulfides to sulfoxides by hydrogen peroxide catalyzed by in situ generated dodecyl hydrogen
sulfate in the absence of organic co-solvents. Adv. Synth. Catal. 2006, 348, 434–438.
43. Jafari, H.; Rostami, A.; Ahmad-Jangi, F.; Ghorbani-Choghamarani, A. Sulfamic acid-catalyzed
oxidation of sulfides to sulfoxides and sulfones using H2O2: Green and chemoselective method.
Synth. Commun. 2012, 42, 3150–3156.
44. Mokhtary, M.; Qandalee, M.; Niaki, M.R. Highly efficient selective oxygenation of sulfides to
sulfoxides by oxalic acid dihydrate in the presence of H2O2. J. Chem. 2012, 9, 863–868.
45. Golchoubian, H.; Hosseinpoor, F. Effective oxidation of sulfides to sulfoxides with hydrogen peroxide
under transition-metal-free conditions. Molecules 2007, 12, 304–311.
46. Menova, P.; Kafka, F.; Dvorakova, H.; Gunnoo, S.; Sanda, M.; Cibulka, R. Pyrazinium salts as
efficient organocatalysts of mild oxidations with hydrogen peroxide. Adv. Synth. Catal. 2011, 353,
865–870.
47. Zurek, J.; Cibulka, R.; Dvorakova, H.; Svoboda, J. N1,N10-Ethylene-bridged flavinium salts derived
from L-valinol: Synthesis and catalytic activity in H2O2 oxidations. Tetrahedron Lett. 2010, 51,
1083–1086.
48. Marsh, B.J.; Carbery, D.R. Chemoselective sulfide oxidation mediated by bridged flavinium
organocatalysts. Tetrahedron Lett. 2010, 51, 2362–2365.
49. Jurok, R.; Cibulka, R.; Dvorakova, H.; Hampl, F.; Hodacova, J. Planar chiral flavinium
salts–Prospective catalysts for enantioselective sulfoxidation reactions. Eur. J. Org. Chem. 2010,
5217–5224.
50. Imada, Y.; Kitagawa, T.; Iwata, S.; Komiya, N.; Naota, T. Oxidation of sulfides with hydrogen
peroxide catalyzed by synthetic flavin adducts with dendritic bis(acylamino)pyridines. Tetrahedron
2014, 70, 495–501.

Molecules 2015, 20
16721
51. Hartman, T.; Herzig, V.; Budesinsky, M.; Jindrich, J.; Cibulka, R.; Kraus, T. Flavin-cyclodextrin
conjugates: Effect of the structure on the catalytic activity in enantioselective sulfoxidations.
Tetrahedron Asymmetry 2012, 23, 1571–1583.
52. Zelenka, J.; Hartman, T.; Klimova, K.; Hampl, F.; Cibulka, R. Phase-transfer catalysis in oxidations
based on the covalent bonding of hydrogen peroxide to amphiphilic flavinium salts. Chemcatchem
2014, 6, 2843–2846.
53. Menova, P.; Dvorakova, H.; Eigner, V.; Ludvik, J.; Cibulka, R. Electron-deficient alloxazinium
salts: Efficient organocatalysts of mild and chemoselective sulfoxidations with hydrogen peroxide.
Adv. Synth. Catal. 2013, 355, 3451–3462.
54. Mojr, V.; Herzig, V.; Budesinsky, M.; Cibulka, R.; Kraus, T. Flavin-cyclodextrin conjugates as
catalysts of enantioselective sulfoxidations with hydrogen peroxide in aqueous media. Chem. Commun.
2010, 46, 7599–7601.
55. Sturala, J.; Bohacova, S.; Chudoba, J.; Metelkova, R.; Cibulka, R. Electron-deficient heteroarenium
salts: An organocatalytic tool for activation of hydrogen peroxide in oxidations. J. Org. Chem. 2015,
80, 2676–2699.
56. Rahimizadeh, M.; Rajabzadeh, G.; Khatami, S.M.; Eshghi, H.; Shiri, A. TiO2 nanoparticles and
Preyssler-type heteropoly acid modified nano-sized TiO2: A facile and efficient catalyst for the
selective oxidation of sulfides to sulfones and sulfoxides. J. Mol. Catal. A Chem. 2010, 323, 59–64.
57. Veerakumar, P.; Lu, Z.Z.; Velayudham, M.; Lu, K.L.; Rajagopal, S. Alumina supported
nanoruthenium as efficient heterogeneous catalyst for the selective H2O2 oxidation of aliphatic and
aromatic sulfides to sulfoxides. J. Mol. Catal. A Chem. 2010, 332, 128–137.
58. Rajabi, F.; Naserian, S.; Primo, A.; Luque, R. Efficient and highly selective aqueous oxidation of
sulfides to sulfoxides at room temperature catalysed by supported iron oxide nanoparticles on SBA-15.
Adv. Synth. Catal. 2011, 353, 2060–2066.
59. Tundo, P.; Romanelli, G.P.; Vazquez, P.G.; Arico, F. Multiphase oxidation of alcohols and sulfides
with hydrogen peroxide catalyzed by heteropolyacids. Catal. Commun. 2010, 11, 1181–1184.
60. Donoeva, B.G.; Trubitsina, T.A.; Maksimov, G.M.; Maksimovskaya, R.I.; Kholdeeva, O.A.
6−
Catalytic properties and stability of the heteropolytungstate P2W21O71(H2O)3 in H2O2-based
oxidations. Eur. J. Inorg. Chem. 2009, 5142–5147.
61. Ezzat, R.; Narges, N. Keggin type heteropoly acid, encapsulated in metal-organic framework:
A heterogeneous and recyclable nanocatalyst for selective oxidation of sulfides and deep
desulfurization of model fuels. J. Mol. Catal. A Chem. 2015, 398, 17–25.
62. Shaabani, A.; Rezayan, A.H. Silica sulfuric acid promoted selective oxidation of sulfides to
sulfoxides or sulfones in the presence of aqueous H2O2. Catal. Commun. 2007, 8, 1112–1116.
63. Rostami, A.; Navasi, Y.; Moradi, D.; Ghorbani-Choghamarani, A. DABCO tribromide immobilized
on magnetic nanoparticle as a recyclable catalyst for the chemoselective oxidation of sulfide using
H2O2 under metal- and solvent-free conditions. Catal. Commun. 2014, 43, 16–20.
64. Islam, S.M.; Roy, A.S.; Mondal, P.; Salam, N.; Paul, S. Polymer-anchored Cu(II) complex as an
efficient catalyst for selective and mild oxidation of sulfides and oxidative bromination reaction.
Catal. Lett. 2013, 143, 225–233.

Molecules 2015, 20
16722
65. Sharma, R.K.; Pandey, A.; Gulati, S. Silica-supported molybdenum complex: A novel, selective and
reusable organic-inorganic hybrid catalyst for eco-friendly oxidation of sulfides and olefins.
Polyhedron 2012, 45, 86–93.
66. Tshentu, Z.R.; Togo, C.; Walmsley, R.S. Polymer-anchored oxovanadium(IV) complex for the
oxidation of thioanisole, styrene and ethylbenzene. J. Mol. Catal. A Chem. 2010, 318, 30–35.
67. Khodaei, M.M.; Bahrami, K.; Arabi, M.S. Oxidation of sulfides to sulfoxides with H2O2/HNO3
reagent system. J. Sulfur Chem. 2010, 31, 83–88.
68. Liu, Z.M.; Zhao, H.; Li, M.Q.; Lan, Y.B.; Yao, Q.B.; Tao, J.C.; Wang, X.W. Chiral phosphoric
acid-catalyzed asymmetric oxidation of aryl alkyl sulfides and aldehyde-derived 1,3-dithianes:
using aqueous hydrogen peroxide as the terminal oxidant. Adv. Synth. Catal. 2012, 354, 1012–1022.
69. Rostami, A.; Hassanian, F.; Ghorbani-Choghamarani, A.; Saadati, S. Selective oxidation of sulfides
to sulfoxides using H2O2 catalyzed by p-toluenesulfonic acid (p-TsOH) under solvent-free conditions.
Phosphorus Sulfur 2013, 188, 833–838.
70. Lakouraj, M.M.; Hasantabar, V. Alumina-supported monoperphosphoric acid for selective oxidation
of sulfides to sulfoxides. J. Sulfur Chem. 2011, 32, 93–98.
71. Zolfigol, M.A.; Khazaei, A.; Safaiee, M.; Mokhlesi, M.; Rostamian, R.; Bagheri, M.; Shiri, M.;
Kruger, H.G. Application of silica vanadic acid as a heterogeneous, selective and highly reusable
catalyst for oxidation of sulfides at room temperature. J. Mol. Catal. A Chem. 2013, 370, 80–86.
72. Shen, H.M.; Ji, H.B. Amino alcohol-modified beta-cyclodextrin inducing biomimetic asymmetric
oxidation of thioanisole in water. Carbohydr. Res. 2012, 354, 49–58.
73. Shen, H.M.; Ji, H.B. Biomimetic asymmetric aldol reactions catalyzed by proline derivatives attached
to beta-cyclodextrin in water. Tetrahedron Lett. 2012, 53, 3541–3545.
74. Shen, H.M.; Ji, H.B. Cyclodextrin-RuCl2(Arene)2 conjugates: Another way to enhance the
enantioselectivity of aromatic ketones reduction by aromatic ligands’ volume. Tetrahedron 2013,
69, 8360–8367.
75. Karimi, B.; Khorasani, M. Selectivity adjustment of SBA-15 based tungstate catalyst in oxidation
of sulfides by incorporating a hydrophobic organic group inside the mesochannels. ACS Catal. 2013,
3, 1657–1664.
Sample Availability: Samples of the compounds are available from the authors.
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