Effective oxidation of sulfides to sulfoxides with hydrogen peroxide under transition-metal-free conditions

Article abstract of DOI:10.3390/12030304

A "green" highly selective oxidation of organic sulfides to the corresponding sulfoxides was developed using hydrogen peroxide and glacial acetic acid under transition metal-free and mild conditions. The oxidation procedure is very simple and the products

Full text of DOI:10.3390/12030304

Molecules 2007, 12, 304-311
molecules
ISSN 1420-3049
http://www.mdpi.org
Communication
Effective Oxidation of Sulfides to Sulfoxides with Hydrogen
Peroxide under Transition-Metal-Free Conditions
Hamid Golchoubian * and Farideh Hosseinpoor
Department of Chemistry, University of Mazandaran, P.O. Box 453, Babolsar, Iran
*
Author to whom correspondence should be addressed. Tel/Fax: (98)-1125242002, E-mail:
h.golchobian@umz.ac.ir, golchoubian@yahoo.com
Received: 10 January 2007; in revised form: 14 February 2007 / Accepted: 18 February 2007 /
Published: 3 March 2007
Abstract: A “green” highly selective oxidation of organic sulfides to the corresponding
sulfoxides was developed using hydrogen peroxide and glacial acetic acid under
transition metal-free and mild conditions. The oxidation procedure is very simple and the
products are easily isolated in excellent yields (90-99%).
Keywords: Sulfide, glacial acetic acid, hydrogen peroxide, selective oxidation, sulfoxide.
Introduction
The growth in the chemistry of organic sulfoxides during last decade was due to their importance
as synthetic intermediates for the production of a wide range of chemically and biologically active
molecules. They often perform a major function as therapeutic agents such as anti-ulcer (proton pump
inhibitor) [1], antibacterial, antifungal, anti-atherosclerotic [2], antihypertensive [3] and cardiotonic
agents [4], as well as psychotonics [5] and vasodilators [6].
The oxidation of sulfides to sulfoxides is the most straightforward synthetic route to the latter, and
numerous reagents and oxidative procedures are available for this transformation. However, many of
them cause overoxidation to the corresponsing sulfones. Therefore, control of the reaction conditions,
that is, time, temperature and the relative amount of oxidants, plays an important role in avoiding the
formation of oxidation side products, but this is often hard to achieve and therefore there is still
considerable interest in the development of selective oxidants for this transformation [7-12].

Molecules 2007, 12
305
Much of the current work in this area focuses on the use of transition-metal catalyzed processes [7-
2]. However, a large number of such oxidation reactions often require the use of toxic metal reagents
2
or catalysts. Consequently, from a Green Chemistry standpoint it is very important to develop a
“
“
green” oxidation system for chemical manufacturing. Hydrogen peroxide is considered as an ideal
green” oxidant due to its strength and lack of toxic by-products. Among the research on the oxidation
of sulfides to the corresponding sulfoxides under transition metal-free conditions [23-33] some most
promising results were reported by Ravikumar et al. [34], in which hydrogen peroxide in solvent of
hexafluoro-2-propanol was used for the selective oxidation of sulfides to sulfoxides. Although the
yields of these reactions were quite high, hexafluoro-2-propanol is poisonous, expensive and volatile,
which severely restrict its practical use in organic synthesis. In continuation of our current studies on
the selective oxidation of hydrocarbons [35-40] we wish to report herein a very efficient and simple
method for the oxidation of sulfides to the corresponding sulfoxides using H O under mild conditions,
2
2
as shown in Scheme 1.
Scheme 1. Oxidation of sulfides to the corresponding sulfoxides.
O
4
equiv 30% H O
2
2
1
2
1
2
R -S-R
R -S-R
r.t, acetic acid
1
2
R , R = benzyl, phenyl, alkyl, aryl, allyl
Results and Discussion
Methyl phenyl sulfide was selected as a model substrate for optimization, and the oxidation of this
substrate in various solvents was studied. Among the solvents examined, glacial acetic acid was the
most effective (Table 1, entries 1-5). The reaction was also carried out at different temperatures under
the same conditions. As the results indicate (Table 1, entries 6-9), the oxidation proceeded to
completion faster at elevated temperatures. Further, when the oxidation of methyl phenyl sulfide was
carried out using different concentrations of hydrogen peroxide, the reaction did not reach completion
2 2
using less than 8 mmol of H O . However, when a large concentration was employed neither the
conversion nor selectivity of the reaction was improved (Table 1, entries 10-13). The large excess of
hydrogen peroxide required was a result of its decomposition in acetic media. The oxygen released in
the decomposition played little role in the oxidation of the sulfides, as proven by the fact that the
oxidation occurred in poor yield when carried out in the absence of hydrogen peroxide by bubbling
molecular oxygen through the reaction mixture under similar reaction conditions (Table 1, entry 14).
In an independent experiment the oxidation of methyl phenyl sulfoxide to the corresponding sulfones
was investigated under the same reaction conditions; no oxidation took place during 120 min and the
starting material was recovered.

Molecules 2007, 12
306
a
Table 1. Oxidations of methyl phenyl sulfide .
H O
mmol)
Solvent
(2 mL)
Time Temp. Conversion
Sulfoxide
Selectivity (%)
2
2
Entry
o
b
b
(
(min) ( C)
(%)
100
0
1
2
3
4
5
6
7
8
9
8
8
8
8
8
8
8
8
8
1
2
5
8
10
-
CH
CH
CH
CH NO
3
COOH
Cl
CN
80
90
90
90
240
440
35
20
8
25
25
25
25
25
0
>99
0
2
2
3
<5
<5
20
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
3
2
CH
CH COOH
CH COOH
3
OH
3
93
3
45
60
80
25
25
25
25
25
25
100
100
100
8
3
CH COOH
CH COOH
3
1
1
1
1
1
0
1
2
3
3
CH COOH
80
80
80
80
75
600
3
CH
CH
CH
CH
CH
3
3
3
3
3
COOH
COOH
COOH
COOH
COOH
13
23
100
100
7
c
1
4
a
In all experiments 2 mmol of substrate were used.
b
c
Isolated yield on the basis of the weight of the pure product obtained.
2
The reaction was carried out under an atmosphere of O instead of in the
presence of 30% H O .
2
2
The oxidations of other sulfides such as diaryl, dibenzyl, dialkyl, diallyl, arylbenzyl, arylalkyl,
benzyl -alkyl, allylphenyl and cyclic sulfides were then examined using the optimized reaction
conditions (Table 2). In all cases, the reactions resulted in 100% conversion of the sulfides. In the case
of benzyl sulfides (Table 2, entries 2 and 6), no oxidation was observed at the benzylic C-H bond.
Similarly, the carbon-carbon double bonds in allyl sulfides remained intact during the oxidation (Table
2
, entries 5 and 8). This procedure can also be applied to the oxidation of cyclic sulfides (Table 2,
entry 10).
a
Table2. Oxidation of sulfides to sulfoxides with hydrogen peroxide .
Time
Conversion
Yield
b
Entry
Substrate
(min
)
Sulfoxide
c
(
%)
(%)
O
S
S
CH3
1
2
80
100
100
100
CH3
99
93
94
S
S
S
120
O
O
S
7
5
3

Molecules 2007, 12
307
Table 2. Cont.
Time
Conversion
%)
Yield
b
Entry
Substrate
(min
)
Sulfoxide
c
(
(%)
CH3
CH3
S
S
4
5
50
35
100
100
92
90
O
S
S
O
6
S
70
100
S
93
O
S
7
8
S
S
50
60
100
100
91
92
O
S
O
9
48
100
90
S
S
S
O
1
1
0
1
30
26
100
100
S
9
6
O
H C
CHO
3
H C
CHO
S
3
S
93
91
O
1
2
2
45
100
S
S
O
a
2 2
mmol of substrate at room temperature and 8 mmol of 30% aqueous H O , in glacial acetic
acid (2 mL) at room temperature.
b
c
The products were identified by comparison of physical and spectroscopic properties with
authentic compounds.
Isolated yields on the basis of the weight of the pure product obtained.
Large scale oxidation of methyl phenyl sulfoxide (2 mol) was also investigated and the results
demonstrated that oxidation took place in good yield (typically less than 2% yield was lost). The
kinetic studies show that the oxidation of sulfide is a second order reaction and is not acid catalyzed,
so the reaction times remained constant as a result of increasing the acidities of the medium by the
addition of trichloroacetic acid at fixed content of acetic acid. However, experiments demonstrate that
dry hydrogen peroxide (percarbonate) in glacial acetic acid does not generate peracetic acid on
standing. Further, kinetic study with peracetic acid under identical reaction conditions reveal that the
oxidation of sulfides is very fast; too fast to follow by titrimetry. Although the exact mechanism of
this transformation is still unclear, the oxidation probably involves the electophilic attack of the
peroxide oxygen on sulfur. Despite the fact that, protonated hydrogen peroxide is a powerful oxidizing

Molecules 2007, 12
308
agent the oxidation of sulfides is rule out by this oxidizing mediator as the reaction is not acid
catalyzed; acetic acid and trichloroacetic acid fail to protonate hydrogen peroxide.
Conclusions
As shown, the proposed system was found to be a selective method for the hydrogen peroxide
oxidation at room temperature of a variety of sulfides to the corresponding sulfoxides. Although the
precise mechanism of this transformation is still uncertain, the oxidation probably involves the
electophilic attack of the peroxide oxygen on the sulfide sulfur atom. Moreover, this oxidation system
is clean, safe and operationally simple and the yields of the products are high, so the oxidation method
meets the needs of contemporary “green chemistry” and is suitable for practical synthesis.
Acknowledgements
We are grateful for the financial support of Mazandaran University of the Islamic Republic of Iran.
Experimental
General
All chemicals were used without further purification as received from different commercial sources
(
Merck, Aldrich, Fluka). All the isolated sulfoxide compounds were identified through comparison of
their GLC (retention time) IR, NMR and melting points with literature data.
General method for the oxidation of sulfides to sulfoxides
Hydrogen peroxide (8 mmol, 30%) was slowly added to the sulfide (2 mmol) in glacial acetic acid
(
2 mL). The reaction mixture was then stirred at room temperature until thin layer chromatography
indicated the reaction was complete. The resulting solution was neutralized with aqueous NaOH (4 M)
and the product was extracted with CH Cl . The organic layer was dried over anhydrous Na SO and
2
2
2
4
then concentrated under reduced pressure to yield analytically pure product. Rate measurements were
made in glacial acetic acid under second order conditions at constant temperature. For each kinetic run
a fresh solution of the oxidant in glacial acetic acid was prepared and standardized iodometrically. The
progress of the oxidation, with the sulfides present in excess over the oxidant, was followed by
iodometric estimation of the unconsumed oxidizing agent.
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