A general and selective zinc-catalyzed oxidation of sulfides to sulfoxides

Article abstract of DOI:10.1016/j.tetlet.2012.06.003

A general zinc-catalyzed oxidation of sulfides to sulfoxides has been developed. All the reactions proceeded at room temperature. Hydrogen peroxide was used as a green oxidant. Twenty-one examples of sulfoxides were prepared in moderate to excellent yields.

Full text of DOI:10.1016/j.tetlet.2012.06.003

Tetrahedron Letters 53 (2012) 4328–4331
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A general and selective zinc-catalyzed oxidation of sulfides to sulfoxides
⇑
Xiao-Feng Wu
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, Zhejiang Province, PR China
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A general zinc-catalyzed oxidation of sulfides to sulfoxides has been developed. All the reactions pro-
ceeded at room temperature. Hydrogen peroxide was used as a green oxidant. Twenty-one examples
of sulfoxides were prepared in moderate to excellent yields.
Received 15 May 2012
Revised 30 May 2012
Accepted 1 June 2012
Available online 13 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Zinc catalyst
Sulfide
Sulfoxide
Oxidation
H2O2
‘Green chemistry’ has become one of the hottest terms in chem-
istry during recent years. And if we related oxidation reaction in
relation with the 12 principles of green chemistry,1 it’s apparently
to have conclusions like increasing the reaction efficiency; using
green oxidant and non-toxic catalyst are the most obvious aspects
we can start. Concerning the green oxidant, hydrogen peroxide is
one of the most powerful candidates besides oxygen, because
it’s cheap, readily available, high atom efficiency, and water is
expected as the only by-product to be generated from the
reaction.2 Regarding the green catalyst, zinc salts hold the features
like inexpensive, non-toxic, abundant and environmental benign.3
To explore zinc-catalyzed organic reactions are both interesting in
academic and also in industrial.
Sulfoxides are an important class of compounds in organic
chemistry with wide applications in chemical synthesis and in
the preparation of biologically active compounds, even applied in
the activation of enzymes.4 Traditionally, sulfoxides were oxidized
from the corresponding sulfides with stoichiometric amount of
organic or inorganic oxidant such as NaOCl and H5IO6 which pro-
duced a large amount of wastes. However, numerous methodolo-
gies have been developed during last decades for the selective
oxidation of sulfides. Good yields of sulfoxides could be obtained
from different catalytic systems based on acid,5 iron,6 vanadium,7
tungsten,8 manganese,9 copper,10 titanium,11 platinum,12 magne-
sium,13 cobalt,14 and silver.15 Interestingly, the group of Beller
found even the hydrogen peroxide itself can promote the reaction
as well.16 Sulfoxides were obtained in excellent yields with good
selectivity at 70 °C under solvent free conditions. As our continual
interest in zinc-catalyzed oxidation reactions,17 taking the
importance of sulfoxides into consideration, and it is more ideal
to perform the oxidation reactions at room temperature in an open
flask, we developed a general zinc-catalyzed oxidation of sulfides
to sulfoxides. All the reactions were carried out at room tempera-
ture, by using hydrogen peroxide as the oxidant combined with
catalytic amount of zinc catalyst; sulfoxides were produced in
good yields and with excellent selectivity. Remarkably, the ligands
applied are commercially available no tedious preparation process
are needed.
Initially, the reaction was carried out with 1 mmol of phenyl
sulfide in 2 mL of dioxane, 50% of conversion was obtained in
the presence of 10 mol % of ZnBr2 using H2O2 (4 mmol) as the
oxidant at room temperature (Table 1, entry 1). Then nine types
of nitrogen ligands were tested (Table 1, entries 2–10). 80–84%
Yields of the sulfoxide with excellent conversions were observed
using pyridine-2,6-dicarboxylic acid as the ligand (Table 1, en-
tries 2–4). To our surprise, only 19% of conversion was observed
with phthalic acid as the ligand (Table 1, entry 5). These results
illustrate the importance of the ligands structure. The other
tested ligands gave decreased conversions and yields (Table 1,
entries 6–10). The effects of ligand and catalyst were also
checked; only 5–15% conversion and 2–4% yields were detected
if we carried out the reaction in the absence of catalyst (Table 1,
entries 11–12). No starting material was converted in the ab-
sence of H2O2 (Table 1, entry 13). After these testing, we chose
pyridine-2,6-dicarboxylic acid as the ligand to test the influence
of zinc salts in dioxane at room temperature (Table 1, entries
⇑
Tel.: +49 381 1281 343.
E-mail address: xiao-feng.wu@catalysis.de
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.003

X.-F. Wu / Tetrahedron Letters 53 (2012) 4328–4331
4329
Table 1
Zinc-catalyzed oxidation of phenyl sulfidea
O
S
O
O
S
[Zn]/H2O2
S
1 mmol
1
2
N
N
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
HO2C
N
N
CO2H
N
L 2
L 3
L 4
L 1
L 8
L 9
CO2H
L 6
N
N
CO2H
L 7
N
H
N
H
CO2H
H
N
N
H
L 5
Entry
[Zn] (10 mol %)
Solvent (2 mL)
L (10 mol %)
Conv.b (%)
Y 1b (%)
Y 2b (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
/
/
ZnBr2
ZnCl2
ZnI2
ZnF2
Zn(OAc)2
ZnSO4Á7H2O
Zn(NO3)2Á6H2O
Zn(acac)2 Â H2O
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
MeOH
/
50
95
>99
96
19
80
55
62
21
15
5
32
80
84
80
10
66
35
39
12
8
2
4
0
47
3
10
9
30
53
3
61
90
70
80
50
8
14
7
8
10
4
5
13
9
3
2
2
L 1
L 2
L 3
L 4
L 5
L 6
L 7
L 8
L 9
L 2
—
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
L 2
15
0
9
0c
20
8
70
15
29
22
50
85
15
82
>99
>99
>99
69
10
90
15
11
11
21
7
8d
5
21
18
10
1
EtOH
MeCN
THF
H2O
ZnBr2
ZnBr2
Acetone
60
28
a
b
c
Zinc salt (10 mol %), ligand (10 mol %), solvent (2 mL), H2O2 (4 mmol, 30% in water), phenyl sulfide (1 mmol), rt, 6 h, air.
Conversion and yield were determined by GC using hexadecane as the internal standard based on phenyl sulfide.
Without additional H2O2.
d
ZnBr2 (5 mol %), L 2 (5 mol %).
14–20). No better results were achieved in all the cases. With
decreased loading of catalyst, lower conversion and yield were
observed (Table 1, entry 21). The solvents testing were carried
out afterwards (Table 1, entries 22–27). To our delight, 90% of
sulfoxide was produced in methanol with total conversion of
starting material and only 5 mol % of sulfone as the over oxi-
dized product was formed (Table 1, entry 22). In most of the
cases, the decomposition of the substrate could also be detected,
which also can explain the difference between yields and
conversion.
was formed by the hydration of the nitrile functional group
(Table 2, entry 9). Amine can be tolerated as well, 93% of 4-(meth-
ylsulfinyl)aniline was formed without the formation of nitro by-
product (Table 2, entry 10). In the cases of using (4-(bromomethyl)
phenyl)(methyl)sulfane, 4-(methylthio)benzaldehyde, (chloro-
methyl)(phenyl)sulfane and (2-chloroethyl)(phenyl)sulfane as
substrates, the reactions were performed in dioxane in order to
avoid the reaction of substrates with solvent and moderate to good
yields of the corresponding products were produced (Table 2,
entries 8, 11, 14 and 15).
With the best reaction conditions in our hand (Table 1, entry
22), we started to check the generality and efficiency of this
methodology (Table 2).18 Various (methylsulfinyl)benzenes were
produced in good to excellent yields with excellent selectivity
(Table 2, entries 2–12). In addition to methoxy-, methyl-, bromo-
, and nitrile-substituted sulfides, (4-(methylsulfinyl)phenyl)meth-
anol was also produced from the corresponding sulfide and only
a small amount of 4-(methylsulfinyl)benzaldehyde was observed
as the oxidation of the benzyl alcohols (Table 2, entry 7). No amide
Besides the substituents on the arene part, vinyl-, benzyl-dec-
orated phenylsulfides were also applied as substrates and gave
53–80% yields (Table 2, entries 16–17). No oxidation of the dou-
ble bond was identified (Table 2, entry 16), and in the case of
benzyl substituent, the decomposition of starting material was
detected (Table 2, entry 17). Moreover, heterocyclic and alkyl
sulfide were successfully applied as substrates as well and gave
the corresponding sulfoxides in good yields (Table 2, entries
19–21).

4330
X.-F. Wu / Tetrahedron Letters 53 (2012) 4328–4331
Table 2
Table 2 (continued)
Zinc-catalyzed oxidation of sulfidesa
Entry
Product
Conv.
>99
Yieldb (%)
66d
Selectb (%)
66
O
S
S
O
S
ZnBr2/L 2, H2O2
MeOH, RT
R'
R'
15
Cl
R
R
O
S
Entry
1
Product
Conv.
>99
Yieldb (%)
Selectb (%)
90
16
17
18
>99
>99
>99
80
53
88
80
53
88
O
S
90
O
S
Ph
O
S
2
3
>99
>99
85
91
85
91
O
S
OH
O
S
O
OMe
19
>99
45
89
45
O
S
S
O
4
5
>99
>99
90
90
95
O
S
N
S
MeO
20
21
>99
>99
89
81
85c
O
S
80c
81
O
S
95
89c
a
ZnBr2 (10 mol %), L 2 (10 mol %), MeOH (2 mL), H2O2 (4 mmol, 30% in water),
sulfides (1 mmol), rt, 6 h, air.
Conversions and yields were determined by GC using hexadecane as the
internal standard based on sulfides.
O
S
b
6
7
8
>99
>99
>99
88
75
88
75
59
c
MeO
HO
Br
Isolated yields.
Dioxane (2 mL) as the solvent.
d
O
S
O
S
In conclusion, a general zinc-catalyzed oxidation of sulfides to
sulfoxides has been developed. The reactions proceeded at room
temperature, and use hydrogen peroxide as the green oxidant.
Twenty-one examples of sulfoxides have been prepared in moder-
ate to excellent yields.
59d
O
S
9
>99
>99
89
89
93
Acknowledgments
NC
O
S
The financial support from the state of Mecklenburg-Vorpomm-
ern and the Bundesministerium für Bildung und Forschung (BMBF)
is gratefully acknowledged. The author also thanks the support and
general advice from Professor Dr. Matthias Beller and Dr. Helfried
Neumann (LIKAT).
10
93
85c
88d
H2N
O
S
11
12
>99
>99
88
89
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18. General comments: All reactions were carried out under air. ZnBr2, pyridine-
2,3-dicarboxylic acid, 1,4-dioxane, THF, MeOH, H2O2 (30% in water) and all the
substrates were purchased from Aldrich and used as received. Gas
chromatography analysis was performed on an Agilent HP-5890 instrument
with a FID detector and HP-5 capillary column (polydimethylsiloxane with 5%
phenyl groups, 30 m, 0.32 mm id, 0.25 lm film thickness) using argon as the
carrier gas. Gas chromatography-mass analysis was carried out on an Agilent
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0.25 mm id, 0.25 lm film thickness) using helium carrier gas. General
procedure for the oxidation of sulfides to sulfoxides: In a 25 mL reaction
tube, ZnBr2 (10 mol %), pyridine-2,6-dicarboxylic acid (10 mol %) and a stirring
bar were added, followed by the addition of sulfides (1 mmol) and MeOH
(2 mL) with syringe. At the end H2O2 (4 mmol; 30% aq) was added in one pot to
the solution. The resulting solution was kept at room temperature for 6 h. Then
hexadecane (100 mg) and ethyl acetate (3 ml) were injected, a part of the
solution was taken for GC and GC–MS analysis after properly mixed. All the
products are commercially available. The GC yields were calculated based on
the calibration with commercially available products, and GC–MS
spectroscopies were also compared.
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