Selective oxidation of sulfides to sulfoxides and sulfones at room temperature using H2O2 and a Mo(VI) salt as catalyst

Article abstract of DOI:10.1016/j.tetlet.2006.04.153

Selective oxidation of sulfides to sulfoxides and sulfones is achieved by H₂O₂ using MoO₂Cl₂ as the catalyst. Various substituted sulfides having functional groups such as methyl, methoxy, bromo, nitro, alkene, alkyne, alcohol, ester, aldehyde and remarkably an oxime are successfully and selectively oxidized without affecting the sensitive functionalities.

Full text of DOI:10.1016/j.tetlet.2006.04.153

Tetrahedron Letters 47 (2006) 4573–4576
Selective oxidation of sulfides to sulfoxides and sulfones
at room temperature using H2O2 and a Mo(VI) salt as catalyst
Kandasamy Jeyakumar and Dillip Kumar Chand*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
Received 3 April 2006; revised 20 April 2006; accepted 28 April 2006
Available online 22 May 2006
Abstract—Selective oxidation of sulfides to sulfoxides and sulfones is achieved by H2O2 using MoO2Cl2 as the catalyst. Various
substituted sulfides having functional groups such as methyl, methoxy, bromo, nitro, alkene, alkyne, alcohol, ester, aldehyde and
remarkably an oxime are successfully and selectively oxidized without affecting the sensitive functionalities.
Ó 2006 Elsevier Ltd. All rights reserved.
O
S
1. Introduction
O
O
b
a
S
S
R
R
R
R
R
R
Sulfoxides and sulfones play important roles in synthetic
organic chemistry.1 These compounds are invariably
prepared from the related sulfides where halogen2,3
and metal4,5-mediated oxidizing systems are usually em-
ployed. However, only a few reports are available where
a given oxidant is suitable for controlled synthesis of
sulfoxides and sulfones.6 It is often noticed that sulfide
oxidation is accompanied by several disadvantages2–5
such as long reaction times, inconvenient reaction condi-
tions, expensive oxidants, undesired side reactions at
other functionalities and low yields. ZrCl4 and H2O2
have been reported recently for the selective oxidation
of sulfides to sulfoxides and sulfones,6g where an excess
of oxidant is used for the synthesis of sulfoxides [sulfide/
30% H2O2/ZrCl4; 2:14:4 in MeOH] and sulfones [sul-
fide/30% H2O2/ZrCl4; 2:20:5 in MeOH].
Scheme 1. Optimized reaction conditions for 4 mmol of substrate.
Reagents and conditions: (a) MoO2Cl2 (1.5 mol %), 30% H2O2
(1.05 equiv), acetone/water (1.5:1), rt; (b) MoO2Cl2 (15 mol %), 30%
H2O2 (4 equiv), acetonitrile, rt.
was examined with a range of sulfides as summarized
in Table 1. A variety of sensitive functional group-con-
taining sulfides were tested to demonstrate the broad
scope of the method therefore, making it unique com-
pared to other oxidants used for selective oxidation.6
We observed selective and quantitative formation of
the desired products without affecting the sensitive func-
tional groups.
Substituted and unsubstituted aryl–alkyl (entries 1–8),
diaryl (entry 9), benzyl–alkyl (entries 10–11) and dialkyl
sulfides (entry 12) were successfully and selectively oxi-
dized to the corresponding sulfoxides and sulfones in
high yields (Table 1).
Recently, MoO2Cl2 has been used as an efficient catalyst
for several organic transformations.7 This communica-
tion deals with the use of MoO2Cl2/H2O2 as an oxidant
for the efficient and selective oxidation of sulfides to
sulfoxides and sulfones at room temperature (Scheme
1). At the onset, the reaction conditions were optimized8
(see Supporting information) for the oxidation of
sulfides to sulfoxides9 [sulfide/30% H2O2/MoO2Cl2; 1/
1.05/0.015 in acetone/water (1.5:1, v/v)] and sulfones10
[sulfide/30% H2O2/MoO2Cl2; 1/4.0/0.15 in acetonitrile]
at room temperature. The efficiency of this method
Sulfides with additional functionalities susceptible to
oxidation or deprotection such as alkenes (entry 13),
alkynes (entry 14), alcohols (entries 15–16), esters (en-
tries 17 and 20), aldehydes (entry 18) and oximes (entry
19) were found to yield sulfoxides and sulfones (Table 1)
without affecting the sensitive functional groups. It is
interesting to note that no epoxidation was observed
during the oxidation of allyl phenyl sulfide (entry 13)
although molybdenum complexes are well known for
epoxidation.11 Phenyl propargyl sulfide was oxidized
*
Corresponding author. Tel.: +91 044 2257 4224; fax: +91 044 2257
4202; e-mail: dillip@iitm.ac.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.153

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K. Jeyakumar, D. K. Chand / Tetrahedron Letters 47 (2006) 4573–4576
a,b
Table 1. Selective oxidation of various functionalized sulfides to sulfoxides/sulfones using H2O2 and MoO2Cl2
Entry
Substrate
Sulfoxidea (A)
Time (min)
Sulfoneb (B)
Yieldc (%)
96
Time (min)
45
Yieldc (%)
95
S
CH3
1
2
3
4
5
6
7
8
9
10
5
5
S
S
S
C2H5
92
93
90
95
92
95
91
89
95
45
45
30
45
30
30
45
35
40
90
93
93
91
92
96
85
91
90
C3H7
5
CH2C6H5
S
20
5
CH3
H3C
H3CO
Br
S
CH3
5
S
CH3
5
S
CH3
10
20
8
O2N
S
CH3
S
S
C2H5
11
12
15
5
96
90
30
15
94
94
CH3
H3C
S
S
13
14
25
15
90
91
50
55
93
90
S
S
OH
15
16
60
10
89d
94
60
30
83
93
S
CH3
HOH2C
S
CH3
17
18
15
10
95
93
30
60
95
96
H3CCO2H2C
OHC
S
CH3
S
CH3
19
20
30
95e
78d
240
93
72
N
HO
N
S
S
180
300
CH2COOC2H5
a Reaction conditions: sulfide (4 mmol), 30% H2O2 (1.05 equiv), MoO2Cl2 (1.5 mol %), 10 mL of acetone/water (1.5:1) mixture, rt.
b Sulfide (4 mmol), 30% H2O2 (4 equiv), MoO2Cl2 (15 mol %), 10 mL of acetonitrile, rt.
c Isolated yield.
d Acetonitrile was used as the solvent.
e Acetone was used as the solvent.

K. Jeyakumar, D. K. Chand / Tetrahedron Letters 47 (2006) 4573–4576
4575
to the sulfoxide/sulfone in good yields (entry 14) with-
out any dimerization. Moreover, alcohol oxidation did
not occur under these conditions as seen in the cases
of 3-(phenylthio)propanol and 4-(methylthio)benzyl
alcohol (entries 15 and 16). The sulfide containing alde-
hyde (entry 18) did not undergo oxidation to the carbox-
ylic acid, whilst the ester groups remained intact (entries
17 and 20).
O
S
MoO2Cl2/1.1 equiv H2O2
CH3CN/rt/5-10 min
S
R
R
R
S
R
S
(95-96%)
R= t-Bu, Ph
Scheme 3. Oxidation of disulfides using H2O2 and MoO2Cl2.
In conclusion, we have described the catalytic role of
commercially available MoO2Cl2 with H2O2 as an effi-
cient oxidant for the selective oxidation of sulfides to
sulfoxides and sulfones. Sulfides with various function-
alities are tolerated under these reaction conditions. Oxi-
mes were also stable with this catalyst system.
Hitherto, there are no reports available for the selective
oxidation of sulfides, which contain an oxime function-
ality. Hence, we chose the substrate, 4-(methylthio)benz-
aldehyde oxime12 (entry 19), and studied its behaviour
towards various oxidants. It is important to note that
oxidants such as VO(acac)2/H2O2,4d MoO2(acac)2/
H2O2,4e NBS/b-cyclodextrin,2b oxone6d and chromium
reagents,4c are used efficiently for sulfide oxidation as
well as for the oxidative cleavage of oximes.13
2. Spectroscopic data for new compounds
2.1. 4-(Methylsulfonyl)benzyl acetate (entry 17B)
Therefore, it was expected that these catalytic systems
would not be suitable for the oxidation of 4-(methyl-
thio)benzaldehyde oxime. Since there were no data
available in the literature, we employed the VO(acac)2/
H2O2 and MoO2(acac)2/H2O2 systems for this oxidation
and observed formation of mixtures of products
(Scheme 2). The crude NMR was used to account for
the amount of various compounds in the mixture. Sur-
prisingly, the MoO2Cl2/H2O2 system was stable towards
the oxime while selectively oxidizing the sulfide to the
sulfoxide and sulfone (Scheme 2).
Liquid. 1H NMR (400 MHz, CDCl3, TMS): d = 2.15 (s,
3H), 3.06 (s, 3H), 5.20 (s, 2H), 7.56 (d, J = 8.2 Hz, 2H),
7.95 (d, J = 8.4 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3, TMS): d = 20.8, 44.5, 65.0, 127.7, 128.5, 140.4,
142.3, 170.5 ppm; IR (neat) m = 1151, 1305, 1745 cmÀ1
.
Anal. Calcd for C10H12O4S (228.0): C, 52.62; H, 5.30.
Found: C, 52.53; H, 5.47. EI-MS m/z: 227.9 (M+, 34%).
2.2. 4-(Methylsulfinyl)benzaldehyde oxime (entry 19A)
Solid, mp: 115–117 °C. 1H NMR (400 MHz, CDCl3,
TMS): d = 2.78 (s, 3H), 7.67 (d, J = 8.4 Hz, 2H), 7.73
(d, J = 8.4 Hz, 2H), 8.17 (s, 1H), 8.76 (s, 1H, OH)
ppm; 13C NMR (100 MHz, CDCl3, TMS): d = 43.7,
124.1, 127.8, 135.4, 146.5, 148.6 ppm. IR (KBr)
The oxidation of disulfides with our system was effective
only for sulfoxides and neither di-sulfoxides nor sulfones
could be obtained even with the use of an excess of H2O2
(Scheme 3).
CH=NOH
95%
1.5 mol% MoO Cl
2
2
1.05 equiv H O
2
2
CH COCH /rt
3
3
SOCH
3
CH=NOH
CH=NOH
15 mol% MoO Cl
2
2
4 equiv H O
2
2
CH CN/rt
3
93%
SCH
3
SO CH
2
3
CH=NOH
+
CH=NOH
+
CH=NOH
CHO
CHO
SCH
1.5 mol% M(acac)
2
+
+
1.05 equiv of H O
2
2
CH COCH /rt
3
3
SCH
3
SOCH
3
SO CH
SOCH
3
2
3
3
M = VO
17%
48%
5%
4%
3%
30%
60%
-
M = MoO 28%
3%
2
Scheme 2. Oxidation of 4-(methylthio)bezaldehyde oxime with various oxidants and conditions.

4576
K. Jeyakumar, D. K. Chand / Tetrahedron Letters 47 (2006) 4573–4576
m = 1028, 1591 cmÀ1. Anal. Calcd for C8H9NO2S
(183.0): C, 52.44; H, 4.95; N, 7.64. Found: C, 52.04;
H, 4.80; N, 7.54. EI-MS m/z: 182.9, (M+, 78%).
5. Sulfones: (a) Chen, Q.; Duan, J. J. Chem. Soc., Chem.
Commun. 1993, 918; (b) Nodiff, E. A.; Lipschutz, S.;
Craig, P. N.; Gordon, M. J. Org. Chem. 1960, 25, 60; (c)
Su, W. Tetrahedron Lett. 1994, 35, 4955; (d) Xu, L.;
Cheng, J.; Trudell, M. L. J. Org. Chem. 2003, 68, 5388; (e)
Choi, S.; Yang, J. D.; Ji, M.; Choi, H.; Kee, M.; Ahn, K.
H.; Byeon, S. H.; Baik, W.; Koo, S. J. Org. Chem. 2001,
66, 8192.
6. (a) Venier, C. G.; Squires, T. G.; Chen, Y.-Y.; Hussmann,
G. P.; Shei, J. C.; Smith, B. F. J. Org. Chem. 1982, 47,
3773; (b) Choudary, B. M.; Bharathi, B.; Reddy, C. V.;
Kantam, M. L. J. Chem. Soc., Perkin Trans. 1 2002, 2069;
(c) McKillop, A.; Tarbin, J. A. Tetrahedron Lett. 1983,
24, 1505; (d) Greenhalgh, R. P. Synlett 1992, 235; (e)
Yamazaki, S. Bull. Chem. Soc. Jpn. 1996, 69, 2955; (f)
Varma, R. S.; Saini, R. K.; Meshram, H. M. Tetrahedron
Lett. 1997, 38, 6525; (g) Bahrami, K. Tetrahedron Lett.
2006, 47, 2009.
7. (a) Chen, C.-T.; Kuo, J.-H.; Pawar, V. D.; Munot, Y. S.;
Weng, S.-S.; Ku, C.-H.; Liu, C.-Y. J. Org. Chem. 2005, 70,
1188; (b) Fernandes, A. C.; Fernandes, R.; Romao, C. C.;
Royo, B. Chem. Commun. 2005, 213; (c) Sanz, R.;
Aguado, R.; Pedrosa, M. R.; Arnaiz, F. J. Synthesis
2002, 856; (d) Sanz, R.; Escribano, J.; Aguado, R.;
Pedrosa, M. R.; Arnaiz, F. J. Synthesis 2004, 1629; (e)
Sanz, R.; Escribano, J.; Fernandez, Y.; Aguado, R.;
Pedrosa, M. R.; Arnaiz, F. J. Synlett 2005, 1389; (f)
Fernandes, A. C.; Romao, C. C. Tetrahedron Lett. 2005,
46, 8881.
8. See Supporting information for details: The reaction
conditions were optimized through the oxidation of
methyl phenyl sulfide using various solvent systems
(acetonitrile, dichloromethane, acetone, acetone/water
and acetonitrile/water) and different amounts of oxidant.
9. Typical procedure for the oxidation of a sulfide to a
sulfoxide: A mixture of 4 mmol of sulfide, 1.05 equiv of
30% aqueous H2O2 (0.480 g), 4 mL of water, 6 mL of
acetone and 1.5 mol % of MoO2Cl2 (0.012 g) was stirred at
room temperature. The reaction was monitored by TLC.
After completion, acetone was evaporated and the crude
mixture was washed with NaHCO3 and extracted with
ethyl acetate. The ethyl acetate was evaporated followed
by flash column purification to obtain the pure sulfoxides.
10. Typical procedure for the oxidation of a sulfide to a
sulfone: A mixture of 4 mmol of sulfide, 4 equiv of 30%
aqueous H2O2 (1.920 g), 10 mL of CH3CN and 15 mol %
of MoO2Cl2 (0.118 g) was stirred at room temperature.
The reaction was monitored by TLC. After completion,
acetonitrile was evaporated and the crude mixture was
washed with NaHCO3 and extracted with ethyl acetate.
The ethyl acetate was evaporated followed by a flash
column purification to obtain the pure sulfone.
2.3. 4-(Methylsulfonyl)benzaldehyde oxime (entry 19B)
Solid, mp: 122–125 °C. 1H NMR (400 MHz, CDCl3,
TMS): d = 3.07 (s, 3H), 7.69 (s, 1H, OH), 7.78 (d,
J = 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2H), 8.19 (s, 1H)
ppm; 13C NMR (100 MHz, CDCl3, TMS): d = 44.5,
127.7, 127.9, 137.5, 141.5, 148.6 ppm. IR (KBr)
m = 1151, 1299, 1595 cmÀ1. Anal. Calcd for C8H9NO3S
(199.0): C, 48.23; H, 4.55; N, 7.03. Found: C, 48.57;
H, 4.32; N, 6.93. EI-MS m/z: 198.8 (M+, 100%).
Acknowledgements
D.K.C. thanks IIT Madras (New Faculty Scheme) and
DST, New Delhi (No. SR/S1/IC-18/2003), for financial
support. K.J. thanks CSIR, New Delhi, for a fellowship.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.04.153.
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