H2O2/Tf2O system: An efficient oxidizing reagent for selective oxidation of sulfanes

Article abstract of DOI:10.1055/s-2008-1067019

A versatile procedure for the oxidation of sulfanes to sulfoxides without any overoxidation to sulfones has been reported. It is noteworthy that the reaction tolerates oxidatively sensitive functional groups and that the sulfur atom is selectively oxidize

Full text of DOI:10.1055/s-2008-1067019

1682
SHORT PAPER
H2O2/Tf2O System: An Efficient Oxidizing Reagent for Selective Oxidation of
Sulfanes
Selective
O
xidation of
oSulfanes to Sh
ulfoxides ammad Mehdi Khodaei,*a,b Kiumars Bahrami,*a,b Ahmad Karimia,b
a
Department of Chemistry, Razi University, Kermanshah 67149, Iran
Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah 67149, Iran
Fax +98(831)4274559; E-mail: mmkhoda@razi.ac.ir; E-mail: Kbahrami2@hotmail.com
b
Received 9 January 2008; revised 22 February 2008
this study. The best results based on yields and times of
the reaction were achieved using ethanol.
Abstract: A versatile procedure for the oxidation of sulfanes to
sulfoxides without any overoxidation to sulfones has been reported.
It is noteworthy that the reaction tolerates oxidatively sensitive
functional groups and that the sulfur atom is selectively oxidized.
Initially, we performed a set of preliminary experiments
on benzyl phenyl sulfane as a model substrate using 30%
Key words: sulfoxides, chemoselectivity, environmentally friend- aqueous hydrogen peroxide in the presence of different
ly, triflic anhydride
amount of triflic anhydride (Tf2O) in ethanol at room tem-
perature. The results are depicted in Table 1. A ratio of
1:2:0.5 sulfane/H2O2/Tf2O was found to be optimum for
complete conversion of sulfanes into sulfoxides.
The selective oxidation of sulfanes to sulfoxides remains
a challenge and is of interest because of the importance of
sulfoxides as synthetic intermediates for the construction
of various chemically and biologically active molecules.1
To date, the most important method of preparation in-
volves the oxidation of sulfanes. Various oxidizing agents
are used for this purpose,2–14 and unfortunately, most of
these reagents are not satisfactory for medium to large-
scale operations for several reasons. The first reason is
that the low content of the effective oxygen that is avail-
able for the oxidation, generation of environmentally un-
favorable by-products, and high cost. Another reason is
that overoxidation of the sulfoxides to sulfones during the
oxidation of sulfanes. Indeed selective oxidation of sul-
fanes to sulfoxides remains a challenging task, and consti-
tutes an active research on its own, particularly with the
emphasis on ‘green chemistry’. In this direction, use of
aqueous hydrogen peroxide as oxidizing agent is highly
preferred in view of an effective oxygen content (47%),
cleanness that produces only harmless water by reaction,15
safety in storage and operation, and the low cost of pro-
duction transportation.16,17 This feature has already stimu-
lated the development of useful procedures for H2O2
oxidation. In continuation of our recent work on the oxi-
dation of sulfanes,18 we disclose that H2O2/Tf2O system
can be used for the gentle and efficient selective oxidation
of a wide range of sulfanes. The route for the synthesis of
sulfoxides is shown in Scheme 1.
Table 1 Effect of Tf2O on the H2O2 Oxidation of Benzyl Phenyl
Sulfanea
Entry
Tf2O (mmol)
Yield (%)b
1
2
3
4
5
0.1
0.2
0.3
0.4
0.5
25
30
50
76
97
a Reactions were performed with benzyl phenyl sulfane (1 mmol), and
H2O2 (2 mmol) for 7 min, at r.t.
b Isolated yield.
To extend the scope of the reaction and to generalize the
procedure, we investigated the sulfoxidation of diaryl,
dibenzyl, aryl benzyl, dialkyl, and heterocyclic sulfanes
under optimized reaction conditions (Table 2). Both sul-
fanes bearing electron-donating and electron-withdraw-
ing substituents gave the desired sulfoxides in excellent
yields. Even a much deactivated sulfane was converted
into the sulfoxide (Table 2, entry 14). All the reactions oc-
curred with complete selectivity for sulfoxide formation,
no overoxidation products such as sulfones were detected
in the reaction mixtures. The chemoselectivity of the pro-
cedure was noteworthy. Under these conditions, various
functional groups including amine and olefin groups were
tolerated (Table 2, entries 17 and 18). These substrates se-
lectively underwent oxidation at the sulfur atom without
undergoing further structural changes in their functional
groups.
Several solvents including acetonitrile, ethanol, acetone,
and 1,4-dioxane were investigated during the course of
O
H2O2, Tf2O
R1
S
R2
R1 R2
S
EtOH, r.t.
Scheme 1
We also have monitored competitive oxidation of sulfanes
in the presence of ester, aldehyde, alcohol, and oxime.
The results are demonstrated in Scheme 2.
SYNTHESIS 2008, No. 11, pp 1682–1684
Advanced online publication: 11.04.2008
DOI: 10.1055/s-2008-1067019; Art ID: Z00608SS
x
x.
x
x
.
2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Selective Oxidation of Sulfanes to Sulfoxides
1683
Table 2 Oxidation of Sulfanes to Sulfoxidesa
H
O
S
O
S
O
S
+
F3C
O
CF3
HO
O
..
OH
HO
O
CF3
Entry R1
R2
Time
(min)
Yield
(%)b,c
– CF3SO3H
O
O
O
H
O
S
O
..
S
1
2
Ph
Bn
7
15
5
97
94
96
96
93
92
95
92
96
94
93
97
99
70
93
95
R1
R2
+
O
CF3
R2
R1
S
+
–
– CF3SO3
Ph
4-O2NC6H4CH2
O
H
.
3
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4CH2
4-ClC6H4
4-ClC6H4
Bn
Bn
.
O
O
–
+ CF3SO3
R1
S
+
R1
S
R2
R2
4
4-MeC6H4CH2
5
– CF3SO3H
5
4-FC6H4CH2
8
Scheme 3 Proposed mechanism for the oxidation of sulfane to the
corresponding sulfoxide with aqueous H2O2 in the presence of Tf2O
6
4-O2NC6H4CH2
35
15
27
7
7
Bn
These observations clearly show that the method is appli-
cable for the selective oxidation of sulfanes in the pres-
ence of the previously mentioned functional groups and
can be considered as a useful practical achievement for
this transformation. The proposed mechanism for the ox-
idation of sulfane to the corresponding sulfoxide is shown
in Scheme 3.
8
4-FC6H4CH2
9
4-MeC6H4CH2
10
11
12
13
14
15
16
Bn
9
4-O2NC6H4CH2
20
15
3
Bn
Bn
Ph
Ph
Ph
In conclusion, we have found that the H2O2/Tf2O system
is an excellent and convenient oxidizing reagent for the
oxidation of sulfanes to sulfoxides without any overoxida-
tion to sulfones in almost quantitative yields. It is note-
worthy that the reaction tolerates oxidatively sensitive
functional groups and that the sulfur atom is selectively
oxidized. Thus, the use of H2O2/Tf2O system is a good ad-
dition to the existing methodologies for the oxidation of
sulfanes.
2,4-(NO2)2C6H3
Ph
60
45
5
Me
N
17
Bn
20
91
N
H
18
19
CH2=CHCH2
Bu
CH2=CHCH2
Bu
15
20
90
93
Melting points were determined in a capillary tube and are not cor-
rected. 1H NMR spectra were recorded on a Bruker 200 spectrome-
ter using TMS as internal standard. IR spectra were recorded on a
Shimadzu IR-470 spectrophotometer using KBr pellets.
a Reaction conditions: H2O2 (2 equiv)/Tf2O (0.5 equiv) in EtOH.
b The products were characterized by comparison of their spectro-
scopic and physical data with those reported in the literature.
c Yields refer to pure isolated products.
In a round-bottomed flask (50 mL) equipped with a magnetic stirrer,
a solution of sulfane (2 mmol) in EtOH (10 mL) was prepared. H2O2
(30%, 4 mmol, 0.4 mL) and Tf2O (1 mmol, 0.17 mL) were added
and the mixture was stirred at r.t. for the time indicated in Table 2.
The progress of the reaction was monitored by TLC (eluent: n-hex-
ane–EtOAc, 7:3). When the starting sulfane had completely disap-
peared, the mixture was quenched by adding H2O (10 mL). The
product was extracted with EtOAc (4 × 5 mL) and the combined ex-
tracts were dried (MgSO4). The filtrate was evaporated and the cor-
responding sulfoxide was obtained as the only product (Table 2).
Analytical and spectral data of representative sulfoxides are given
below.
O
Ph
S
Ph
+
Ph S
Ph
PhCO2Me
100%
+
PhCO2Me
92%
O
+
Ph
S
Me
4-MeC6H4CHO
100%
Ph
Ph
S
Me
Bn
4-MeC6H4CHO
+
BnOH
+
93%
O
Benzyl Phenyl Sulfoxide
S
Ph
S Bn
BnOH
+
Mp 121–123 °C (Lit.19 mp 122–124 °C).
95%
100%
IR (KBr): 1034 cm–1.
O
1H NMR (200 MHz, CDCl3): d = 4.03 (d, J = 12.53 Hz, 1 H), 4.13
(d, J = 12.53 Hz, 1 H), 7.00–7.04 (m, 2 H), 7.28–7.32 (m, 3 H),
7.41–7.49 (m, 5 H).
+ Ph
C
+
Ph
C
H
Bu S
Bu
Bu
S
Bu
NOH
NOH
H
100%
91%
Dibenzyl Sulfoxide
Scheme 2 Reagents and conditions: substrates (1 equiv each), Tf2O
(0.5 equiv), H2O2 (2 equiv), EtOH, r.t.
Mp 130–132 °C (Lit.20 mp 132–134 °C).
IR (KBr): 1026 cm–1.
Synthesis 2008, No. 11, 1682–1684 © Thieme Stuttgart · New York

1684
M. M. Khodaei et al.
SHORT PAPER
1H NMR (200 MHz, CDCl3): d = 3.83 (d, J = 12.8 Hz, 2 H), 3.91 (d,
J = 12.8 Hz, 2 H), 7.26–7.39 (m, 10 H).
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Diphenyl Sulfoxide
Mp 70–72 °C (Lit.21 mp 68 °C).
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IR (KBr): 1038 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.41–7.50 (m, 6 H), 7.61–7.66 (m,
4 H).
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Methyl Phenyl Sulfoxide
Mp 28–30 °C (Lit.19 mp 28–30 °C).
IR (neat): 1050 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.73 (s, 3 H), 7.51–7.55 (m, 3 H),
7.65–7.70 (m, 2 H).
Dibutyl Sulfoxide
Mp 30–31 °C (Lit.19 mp 30–31 °C).
IR (neat): 1022 cm–1.
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1.50 (m, 4 H), 1.70 (quint, J = 7.4 Hz, 4 H), 2.57–2.67 (m, 4 H).
Acknowledgment
We are thankful to the Razi University Research Council for partial
support to this work.
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Synthesis 2008, No. 11, 1682–1684 © Thieme Stuttgart · New York