A Mild, Efficient and Highly Selective Oxidation of Sulfides to Sulfoxides Catalyzed by Lewis Acid–Urea–Hydrogen Peroxide Complex at Room Temperature

Article abstract of DOI:10.1007/s10562-017-2126-1

Alkyl and aryl sulfides were oxidized to the corresponding sulfoxides with urea–hydrogen peroxide (UHP) in the presence of FeCl₃ as a Lewis acid catalyst under simple and mild reaction conditions. The protocol is efficient and highly selective

Full text of DOI:10.1007/s10562-017-2126-1

Catal Lett
DOI 10.1007/s10562-017-2126-1
A Mild, Efficient and Highly Selective Oxidation of Sulfides
to Sulfoxides Catalyzed by Lewis Acid–Urea–Hydrogen Peroxide
Complex at Room Temperature
Mojtaba Azizi1,2 · Ali Maleki1 · Farahman Hakimpoor2 · Reza Ghalavand1 ·
Ali Garavand2
Received: 27 May 2017 / Accepted: 19 June 2017
© Springer Science+Business Media, LLC 2017
Abstract Alkyl and aryl sulfides were oxidized to the cor-
responding sulfoxides with urea–hydrogen peroxide (UHP)
in the presence of FeCl3 as a Lewis acid catalyst under sim-
ple and mild reaction conditions. The protocol is efficient
and highly selective and sulfoxides were obtained as the
sole oxidation products in high yields at room temperature.
Keywords UHP · Oxidation · Sulfides · Sulfoxides ·
FeCl3
1 Introduction
Organosulfur compounds, particular sulfoxides, are use-
ful synthetic reagents in organic chemistry. The selective
oxidation of sulfides to sulfoxides is a fundamental and
important functional group transformation. The chemis-
try of sulfoxides has been attractive to organic chemists;
because, they are valuable synthetic intermediates for the
construction of chemically and biologically important
significant molecules [1–5]. In addition, some of biologi-
cally active sulfoxides play an important role as therapeu-
tic agents such as anti-ulcer [6–8], antibacterial [9] and
anti-atherosclerotic [10, 11]. The increasing interest in
and applications of sulfoxides have prompted investiga-
tions on novel methodologies for the preparation of these
compounds. Even though, various approaches have been
reported for the oxidation of sulfides to sulfoxides, such
as H2O2/iron(III)–salen [12], tert-butyl hydroperoxide/
Ti(iPrO)4/1,2-diphenylethane-1,2-diol [13], TaCl5/H2O2
[14], sodium perborate or 2,2,2-trifluoroacetophenone/
H2O2 [15], 3-carboxypyridinium chlorochromate/AlCl3
[16], ceric ammonium nitrate (CAN) supported on silica/
NaBrO3 [17], H2O2/N-hydroxysuccinimide [18], Some of
these methods suffer from some disadvantages like long
reaction time, expensive reagents and catalysts, difficul-
ties in products isolation and formation of over-oxidation
products.
Graphical Abstract
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-017-2126-1) contains supplementary
material, which is available to authorized users.
* Ali Maleki
maleki@iust.ac.ir
1
Catalysts and Organic Synthesis Research Laboratory,
The use of H2O2 as an oxidant has been studied exten-
sively. Compared to catalytic methods that require other
oxidants such as NaOCl, the use of aqueous H2O2 offers
the advantage that it is a cheap, environmentally benign,
Department of Chemistry, Iran University of Science
and Technology, Tehran 1684613114, Iran
2
Department of Chemistry, Faculty of Science, Lorestan
University, Khoramabad, Iran
Vol.:(0123456789)
1 3

M. Azizi et al.
readily available reagent and water is the only expected
by-product [19–21]. In order to improve above-mentioned
drawbacks and during the course of our studies on the
development and introduce new routes and reagents for the
oxidation reactions [22–24], we became interested to apply
a new catalytic method for the conversion of sulfides to sul-
foxides using urea–hydrogen peroxide (UHP)/FeCl3 system
in acetonitrile at room temperature.
CDCl3) δ: 63.44, 125.62, 126.03, 128.43, 128.55, 128.63,
130.36, 132.02, 141.89.
3 Results and Discussion
The use of Lewis-acid catalyst in modern organic synthe-
sis has been studied extensively during the last decade. The
research is focused on the more versatile, more selective
and more reactive catalyst [25, 26]. A large number of such
oxidation reactions often require the use of metal reagents
or catalysts. Recently transition metals extensively have
been used as catalyst for beside H2O2 as oxidant. However,
one of the problems frequently encountered in metal-cat-
alyzed oxidation with peroxide is the concomitant decom-
position of it, which makes the use of an excess amount of
H2O2 necessary to reach full conversion [27, 28].
2 Experimental
2.1 Materials and Methods
All chemicals were purchased from Merck and Aldrich
chemical companies. Infrared spectra were recorded on
ABB FTLA 2000 Bruker FTIR spectrophotometer. 1H
NMR and 13C NMR spectra were recorded on Bruker AQS
300 Avance spectrophotometer in CDCl3 as the solvent and
TMS as the internal standard. Preparative TLC was per-
formed using silica gel Kieselgel 60 PF254+366. All yields
refer to isolated products.
Because of the safety problems associated with the use
of concentrated solution of H2O2 and overcoming above
mentioned deficiency, it has been adducted with some car-
rier. Among these adducts, UHP is an inexpensive, stable,
mild and easy to handle source of pure H2O2. In continua-
tion of our studies on introducing of UHP as an ideal green
reagent in organic synthesis, it was successfully utilized as
a green oxidant due to its strength and lack of toxicity of
by-products, mild oxidant due to the effective oxygen con-
tent, safety in storage and operation and environmentally-
friendly character, for promotion of oxidation of sulfides to
sulfoxides via this transformation [29, 30].
2.2 General Procedure: Oxidation Reactions Catalyzed
by UHP/FeCl3 System in CH3CN as Solvent
In a 25 round-bottomed flask, to a solution a sulfide
(1 mmol) in CH3CN (10 mL), UHP (1.5 mmol) and FeCl3
(1 mmol) were added successively and the mixture was
stirred magnetically at room temperature. The reaction pro-
gress was followed by TLC (eluent: n-hexane/ethyl acetate:
2:1). After completion of the reaction, the solvent was
removed under vacuum and the residue was quenched by
adding water (15 mL), extracted with CH2Cl2 (3×10 mL).
The combined organic layers were washed with water,
dried over MgSO4 and the solvent was removed in vacuum.
The residue was purified by chromatography on silica gel
(25–30 mesh), eluting with ethyl acetate/n-hexane to give
pure sulfoxides.
In this work, the applicability of the UHP/FeCl3 system
was examined for the oxidation of diaryl, dibenzyl, aryl
benzyl, alkyl benzyl and dialkyl sulfides at room tempera-
ture. For further studies, benzylphenyl sulfide was selected
as a model substrate and a variety of reaction conditions
were performed to optimize the reaction conditions. For
this reason different solvents, Lewis acid catalysts and rela-
tive amount of reagents were studied. Results are described
below.
In general, hydrogen peroxide adducts are not able to
oxidize organic compounds by themselves, therefore intro-
duction of an inorganic catalyst or organic mediator for
active oxygen transfer of these adducts is a necessity in oxi-
dation systems where they are used. To illustrate the need
of catalyst, an experiment was conducted in which the reac-
tion of benzyl phenyl sulfide as model substrate was stud-
ied in the absence of Lewis-acid catalyst. As expected the
reaction did not occur even after 14 h. Therefore, FeCl3 is
an essential component of the reaction. In order to investi-
gate the reaction media, different solvents were examined
in the model reaction. It was found that the reaction time
in acetonitrile was very faster than other solvents (Table 1).
Therefore, it was selected as the best solvent for further
studies.
All the products were known compounds and were
identified by comparison of their melting points with
those authentic literature samples, and also characterized
1
by FT-IR, H NMR and 13C NMR spectral data analyses.
Spectral data and physical properties of benzyl phenyl sul-
foxide as a model reaction are as below:
2.2.1 Spectral Data of a Selected Product
2.2.1.1 Benzyl Phenyl Sulfoxide White crystalline solid,
M.p.: 122°C. IR (KBr): 3065, 2952, 1447, 1041, 744,
697 cm−1. 1H NMR (300 MHz, CDCl3) δ: 4.05 (d, 1H,
J=12.6 Hz), 4.24 (d, 1H, J=12.6 Hz), 7.048–7.079 (m,
2H), 7.23–7.26 (m, 2H), 7.50 (m, 5H). 13C NMR (75 MHz,
1 3

A Mild, Efficient and Highly Selective Oxidation of Sulfides to Sulfoxides Catalyzed by Lewis…
Table 1 Solvent optimization for the oxidation of benzyl phenyl sul-
Table 3 Optimization of relative amount of catalyst and oxidant for
foxide (1 mmol)
the oxidation of benzyl phenyl sulfoxide (1 mmol) in acetonitrile
(10 mL) at room temperature
Entry
Solvent
Time (h)
Yield (%)a
Entry
Oxidant (mmol)
FeCl3 (mmol)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
CH3CN
CH2Cl2
CHCl3
CH3OH
CH3COCH3
H2O
18
8
10
16
8
8
12
43
Trace
13
1
2
3
4
5
6
7
8
UHP (0.5)
UHP (1)
UHP (0.5)
UHP (1)
UHP (1.5)
UHP (2)
UHP (1.5)
UHP (2)
UHP (1.5)
UHP (1.5)
UHP (2)
UHP (2)
H2O2 (1.5)
H2O2 (2)
0.5
0.5
1
18
16
21
15
10
8
2.5
2.5
2.5
3.5
3
43
69
48
76
89
91
96
96
96
96
96
N.R.
45
28
1
Trace
Trace
14
0.5
0.5
1
1
1.5
1
1.5
–
1
C2H5OH
Reaction conditions: UHP (0.5 mmol), FeCl3 (0.5 mmol), acetonitrile
(10 mL), r.t.
9
aIsolated yields
10
11
12
13
14
10
10
10
After examination of different Lewis-acids, we also have
observed that FeCl3 was the best among others such as
AlCl3, ZrCl4, ZnCl2, FeCl2, MnCl2, CoCl2 and TiCl3. The
results are shown in Table 2.
–
N.R.
aIsolated yields and N.R. means no reaction
Then similar reactions were studied in the presence
of various amounts of catalyst and oxidant. As shown in
Table 3, a ratio of 1:1.5:1 mmol of sulfide/UHP/FeCl3 was
found to be optimum for complete conversion of sulfides to
sulfoxides.
methylphenyl sulfide and diphenyl sulfide in the presence
of UHP/FeCl3 catalytic system with the previous meth-
ods in the literatures (see Tables S1 and S2 in Supporting
Information). It is obvious that described procedure in this
research project shows good reaction time than the other
catalysts, which has been reported previously. Also this cat-
alytic system is comparable in terms of price, non-toxicity,
stability and easy separation.
In order to investigate the generality and applicability
of the present catalytic system in this new protocol syn-
thesis of sulfoxides, a variety of products were synthesized
under the optimized conditions. The results summarized in
Table 4 indicate that all sulfoxide products were obtained
selectively in good-to-excellent yields after appropriate
reaction times at room temperature, and no over oxidation
to sulfones were detected in the reaction mixtures.
Moreover, in order to examine the efficiency of this
procedure, we compared the results of the oxidation of
As it can be seen, the applicability of the UHP/FeCl3
system was examined for the oxidation of diaryl, diben-
zyl, aryl benzyl, alkyl benzyl and dialkyl sulfides at room
temperature. In compare of other Lewis-acid catalysts,
FeCl3 has many advantages. It is cheap, nontoxic, and com-
mercially available. Another significant advantage of this
method is that only 1 mmol of the catalyst and 1.5 mmol
of oxidant were required for sulfoxidation reaction while
the oxidation of sulfides to sulfoxides by H2O2 mediated in
the presence of TiCl3 and ZrCl4 was employed more than
1 equivalent of these catalysts per mole of sulfide and an
excess of oxidant is used for the synthesis of sulfoxides
[sulfide/30% H2O2/ZrCl4; 2:14:4] [27].
Table 2 Lewis-acid optimization for the oxidation of benzyl phenyl
sulfoxide (1 mmol)
Entry
Lewis acid
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
–
14
16
16
16
16
12
13
10
12
N.R.
45
35
35
69
17
27
24
20
FeCl2
MnCl2
CoCl2
FeCl3
ZnCl2
AlCl3
ZrCl4
TiCl3
Moreover, UHP as an inexpensive, commercially avail-
able, stable solid and anhydrous source of H2O2 has been
used that is more selective and safer than H2O2· due to its
effective oxygen content. Interestingly, herein, over oxida-
tion of sulfides to sulfones was not detected in any of the
reactions even by using additional amount of catalytic sys-
tem or increasing the time (Table 3, entries 8–11). There-
fore, the present method is highly selective to sulfoxide
formation as the sole oxidation product in high yield and
purity.
Reaction conditions: UHP (1 mmol), FeCl3 (0.5 mmol), acetonitrile
(10 mL), r.t.
aIsolated yields and N.R. means no reaction
1 3

M. Azizi et al.
Table 4 Oxidation of sulfides to sulfoxides in the presence of FeCl3/UHP
Entry
R1
R2
Time (min)
Yield (%)a
Melting point
Found
Reported
1
2
3
4
5
6
7
8
Ph
PhCH2
PhCH2
PhCH2
PhCH2
Ph
PhCH2
PhCH2
CH3
150
150
150
140
180
135
120
120
115
120
125
130
96
96
94
96
96
97
97
95
92
94
93
96
122
121–122 [31]
126–127 [32]
139–140 [33]
70–71.5 [34]
72–73 [35]
121–122 [32]
133–135 [35]
45–46 [36]
Oil [32]
4-Cl–C6H4
4-Br–C6H4
n-Octyl
Ph
4-Me–C6H4
PhCH2
4-Cl–C6H4
n-Butyl
Ph
4-Br–C6H4
4-Br–PhCH2
128–129
138–140
71–72
73.5
123–125
133–134
44–45
Oil
9
n-Butyl
CH3
CH3
10
11
12
Oil
73–75
138–139
Oil [32]
72–75 [35]
139–140 [27]
PhCH2
aIsolated yields
As shown in Fig. 1a, according to FT-IR spectrum, the
presence of a strong absorption peak at near 1041 cm−1
is related to S=O stretching vibration that approved the
formation of benzyl phenyl sulfoxide as a sole product.
In addition, 1H NMR spectrum clearly confirmed the
successful conversion of benzyl phenyl sulfide to benzyl
phenyl sulfoxide (Fig. 1b).
Fig. 1 FT-IR (a) and 1H NMR (b) spectra of benzylphenyl sulfoxide
1 3

A Mild, Efficient and Highly Selective Oxidation of Sulfides to Sulfoxides Catalyzed by Lewis…
11. Yoshida S, Kasuga SH, Hayashi NO, Ushiroguchi TS, Matsuura
Obviously, in the case of sulfone formation, we must
have seen the strong asymmetric and symmetric absorp-
tion peaks of SO2 near 1300 and 1150 cm−1, respectively.
Therefore, the absence of these two absorption peaks and
appearance of only one strong S=O stretching peak at near
1041 cm−1 confirms the selective oxidation of sulfide to
sulfoxides.
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In conclusion, we have introduced a simple, efficient, selec-
tive and eco-friendly procedure for the oxidation of vari-
ous sulfides to sulfoxides using UHP catalyzed by FeCl3
at room temperature. The method offers several notewor-
thy advantages including non-toxic, inexpensive catalyst,
high-to-excellent yields of the products and easy work-up
procedure.
20. Rayati S, Nejabat F, Zakavi S (2014) Inorg Chem Commun
40:82
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24. Fayyaz F, Rahimi R, Rassa M, Maleki A (2015) Water Sci Tech-
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Acknowledgements We thank the research councils of the Iran Uni-
versity of Science and Technology and Lorestan University for their
partial financial support of this research.
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