Nitric acid in the presence of supported P2O5 on silica gel: An efficient and novel reagent for oxidation of sulfides to the corresponding sulfoxides

Article abstract of DOI:10.1016/j.tetlet.2005.06.052

This paper describes an efficient and easy method for oxidation of sulfides 1 to their corresponding sulfoxides 2 with nitric acid in the presence of supported P₂O₅ on silica gel under solvent-free conditions in high yields.

Full text of DOI:10.1016/j.tetlet.2005.06.052

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5503–5506
Nitric acid in the presence of supported P O on silica gel:
2
5
an efficient and novel reagent for oxidation of sulfides to
the corresponding sulfoxides
a,b,
a
Behzad Kooshki and Arnold E. Ruoho
a
*
Abdol R. Hajipour,
a
Pharmaceutical Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
b
Received 16 May 2005; revised 11 June 2005; accepted 13 June 2005
Available online 5 July 2005
Abstract—This paper describes an efficient and easy method for oxidation of sulfides 1 to their corresponding sulfoxides 2 with nitric
acid in the presence of supported P on silica gel under solvent-free conditions in high yields.
2005 Elsevier Ltd. All rights reserved.
2 5
O
ꢀ
Sulfoxides play an important role in organic chemis-
1
ica gel was prepared by mixing a mixture of P O and
2 5
–4
try.
carbon bond formation reactions and as versatile build-
They have been utilized extensively in carbon–
silica gel (0.063–0.2mm) in a mortar and grinding with
a pestle for 1 min to obtain a homogenous mixture. This
reagent is stable and can be kept at room temperature
for months without losing its activity. Sulfides 1 are
mixed with 1 equiv of P O /silica gel in a mortar and
5
,6
ing blocks in organic synthesis. Oxidation of sulfides
is a very useful route for preparation of sulfoxides. Sev-
eral methods are available for conversion of sulfides to
2
5
7
–22
sulfoxides.
However, most of the existing methods
then oxidized with one equivalent of HNO 64% to
3
2
7
use expensive, toxic, or rare oxidizing reagents that are
difficult to prepare. Many of these procedures also suffer
from poor selectivity and also often suffer from lack of
generality and economic applicability. Therefore, there
is a need for a simple, less expensive, general, and safer
method for conversion of sulfides to sulfoxides. Reac-
tions under solvent-free conditions have received
increasing attention in recent years. The main advantage
of these methods over conventional homogenous reac-
tions is that they provide greater selectivity, proceed
with enhanced reaction rates, give cleaner products,
the corresponding sulfoxides 2 (Table 1, Scheme 1).
After extraction of the product with ether and evaporat-
ing the solvent, the product was purified by column
chromatography to produce the product in excellent
yields and short a reaction time. This method offers a
simple, general, selective, highly efficient, and green
route for converting sulfides 1 to their corresponding
sulfoxides 2 without over oxidation. As shown in Table
1 the reaction time for oxidation is short, the reaction
time for aromatic sulfides with electron withdrawing
groups is longer than aromatic sulfides with electron
releasing groups.
2
3,24
and involve simple manipulation.
In continuation of our ongoing program to develop effi-
3–26
The generality of the method was examined using alkyl
aryl, dialkyl, diaryl, cyclic sulfides, and also aryl disul-
fides. It was discovered that a wide variety of sulfides
can be selectively oxidized by this inexpensive reagent
under mild conditions (Table 1). The rate of the reac-
tions of arylalkyl and diaryl sulfides are not dependent
on the substituents of the aromatic ring. The reagent
was chemoselective, tolerating various functional
groups, such as, methoxy, carbonyl, hydroxy, nitro, ni-
trile, C@C double bonds, and halide. This method is a
versatile procedure for synthesis of a-chloro sulfoxides
2
cient reagents for oxidizing organic compounds,
we
now wish to report a facile and selective method for oxi-
dation of sulfides 1 to their corresponding sulfoxides 2
with 64% nitric acid in the presence of supported P O
2
5
on silica gel under solvent-free conditions. The P O /sil-
2
5
2 5
Keywords: Nitric acid; Supported P O ; Sulfides; Sulfoxides.
*
Corresponding author. Tel.: +983113913262; fax: +983113912350;
e-mail: haji@cc.iut.ac.ir
0
040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.052

5504
A. R. Hajipour et al. / Tetrahedron Letters 46 (2005) 5503–5506
a,b
3 2 5
Table 1. Oxidation of sulfides to sulfoxides with 64% HNO in the presence of P O /silica gel
c
Yield (%)
Entry
1
R
1
R
2
Reaction time (min)
Ph
Me
4
6
6
6
5
5
5
6
8
5
8
80
5
5
5
5
6
5
7
6
8
5
8
8
98
98
95
96
92
93
95
85
83
93
82
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
Ph
n-Bu
PhCH
Me
Ph
2
PhCH
2
PHCH
2
n-Bu
PhCH
Me
PhCH
2
2
4-MeC
6
H
4
4-ClC
6
H
4
Me
C
4
H
9
4 9
C H
0
1-Naphthyl
Pr
Me
Pr
1
2Allyl
Allyl
6
3
4
5
6
7
8
9
0
Ph
CH
CH
2
Cl
Cl
88
87
90
89
93
97
94
92
84
95
90
92
6 4
4-MeC H
2
1-Naphthyl
1-Naphthyl
PhCH
2
CH
Me
Me
Me
Me
2
Cl
4-NO
4-CHOC
4-OHCH
4-NCC
2
C
6
H
4
6
H
4
2
C
6
H
4
6
H
4
1
Ph
2
CH
Cl
2
OH
CH
2
3
3
4-MeOC
6
H
4
CH
—
2
–(CH
–(CH
2
)
)
4
–
2
3
–
—
O
24
—
6
89
2
5
—
S
d
2
6
—
5
80
s
S
S
e
78
S
2
2
7
8
—
—
6
6
Tol
Ph
Tol
f
S
S
74
Ph
a
b
c
d
e
f
14–19
Confirmed by comparison with authentic samples.
Substrate/oxidant (1:1.2mmol).
Yield of isolated pure products.
10% disulfoxide.
15% disulfoxide.
12% disulfoxide.
O
S
from their corresponding sulfides (Table 1, entries 13
and 14). Also this procedure is useful for partial oxida-
tion of formaldehyde S,S-diphenyl acetal to the corre-
sponding monosulfoxides in good yields (Table 1,
entries 26–28).
S
P2O5 /silica gel
Solid-state
R1
2
HNO (65%)
R1
R2
R +
3
1
2
1
2
R , R = Alkyl and Aryl
The possible mechanism for oxidation of sulfides 1 to
the corresponding sulfoxides 2 using nitric acid in the
Scheme 1.
silica gel
2
H PO + N O
+
P2O5 + 2H O
3
4
2
5
2
HNO3
2
grinding
+
NO3-
O+
N O
O
N
2
5
R1
O-
O
R1
O-
O
R1
NO3-
S
N
S+
N
N
O
S
N
R2
1
O
R2
O+
O+
R2
O+
R1
R2
H O
2
S
O
+ HNO + HNO
3 2
2
Scheme 2.

A. R. Hajipour et al. / Tetrahedron Letters 46 (2005) 5503–5506
5505
presence of supported P O on silica gel under solvent-
2
free conditions is outlined in Scheme 2.
Yakabe, S.; Clark, J. H.; Morimoto, T. J. Chem. Soc.,
Perkin Trans. 1 1996, 2693.
6. Ali, M. H.; Bohnert, G. J. Synthesis 1998, 1238.
7. For reviews see: (a) Madesclaire, M. Tetrahedron 1986, 42,
5
1
1
In conclusion, we report an easy and versatile method
for converting sulfides to their corresponding sulfoxides
with the following advantages: (a) our reagent is inex-
pensive and can be easily handled, can be stored for
months without losing its activity. (b) The procedure is
simple and occurs under solvent-free conditions at room
temperature. (c) The yield of sulfoxide is high and the
reaction time is short. (d) The isolation of the product
is straightforward.
5459; (b) Mata, E. G. Phosphorus Sulfur Silicon 1996, 117,
231.
1
8. (a) Ogawa, A.; Nishiyama, T.; Kambe, N.; Murai, S.;
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2
2
2
0. Karimi, B.; Ghoreishi-Nezhad, M.; Clark, J. H. Org. Lett.
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1. Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-Q.; Noyori, R.
Tetrahedron 2001, 57, 2469.
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Acknowledgments
1
977.
We gratefully acknowledge the funding support
received for this project from the Isfahan University
of Technology (IUT), IR Iran (A.R.H.), and Financial
support from the research affairs, Yazd University,
Yazd, Iran. Further financial support from Center of
Excellency in Chemistry Research (IUT) is gratefully
acknowledged.
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Chem. 2002, 67, 8622; (b) Hajipour, A. R.; Ruoho, A. E.
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2
1
1
6
7
8
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1
1
1
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27. Preparation of reagent [P O /silica gel (64%, w/w)]: In a
2
5
2 5
mortar 4.5 g of P O (31.69 mmol) and 2.5 g of silica gel
5. (a) Hirano, M.; Yakabe, S.; Itoh, S.; Clark, J. H.;
Moromoto, T. Synthesis 1997, 1161; (b) Hirano, M.;
(0.063–0.2 lm) was ground for 1 min to a homogeneous
mixture.

5506
A. R. Hajipour et al. / Tetrahedron Letters 46 (2005) 5503–5506
Typical procedure for oxidation of sulfides 2 to sulfoxides
with reagent 1: In a mortar, 0.2g of P /silica gel
64%, w/w) (1 mmol) and thioanisole (1 mmol, 0.124 g)
was ground for 30 s and then 0.5 ml of HNO 65%
was added and the mixture was ground with a pestle
for 4 min. After disappearance of the starting sulfide
monitored by TLC using EtOAc–cyclohexane (2:8), the
The solvent was removed under reduced pressure. The
3
(
2
O
5
residue was purified by column chromatography using
silica gel (EtOAc–cyclohexane, 2:8) to afford methyl
phenyl sulfoxide as a colorless oil in 98% yield as
3
1
16
revealed from H NMR analysis, mp 30–32 ꢁC [Lit.
1
mp 32–33 ꢁC]. H NMR (CDCl
3H), 7.48–7.56 (m, 3H), 7.64–7.67 (m, 2H). IR (film): 692,
3
, 300 MHz): d = 2.7 (s,
product was extracted by Et
through a sintered glass funnel, and dried (MgSO
2
O (2 · 10 ml) and filtered
).
754, 954, 1046, 1092, 1415, 1446, 1477, 2915, 3000,
3062cm
À1
4
.