Selective oxidation of sulfides to sulfoxides and sulfones using hydrogen peroxide (H2O2) in the presence of zirconium tetrachloride

Article abstract of DOI:10.1016/j.tetlet.2006.01.051

Hydrogen peroxide (H₂O₂) in the presence of zirconium tetrachloride is a very efficient reagent for the oxidation of sulfides to sulfoxides and sulfones in methanol at room temperature. It is noteworthy that under such conditions, the sulfide function is highly reactive, and various other functional groups such as alkenes and a ketone are tolerated.

Full text of DOI:10.1016/j.tetlet.2006.01.051

Tetrahedron Letters 47 (2006) 2009–2012
Selective oxidation of sulfides to sulfoxides and sulfones
using hydrogen peroxide (H2O2) in the presence of
zirconium tetrachloride
K. Bahrami*
Department of Chemistry, Razi University, Kermanshah 67149, Iran
Received 30 November 2005; revised 22 December 2005; accepted 12 January 2006
Available online 3 February 2006
Abstract—Hydrogen peroxide (H2O2) in the presence of zirconium tetrachloride is a very efficient reagent for the oxidation of sul-
fides to sulfoxides and sulfones in methanol at room temperature. It is noteworthy that under such conditions, the sulfide function is
highly reactive, and various other functional groups such as alkenes and a ketone are tolerated.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
tion,17 The activator is essential for the success of the
reaction because H2O2 oxidizes sulfides rather slowly.
A novel method for activating hydrogen peroxide using
titanium(III) chloride, was described by Shigerue and
co-workers.18 Herein, we describe the successful use of
the H2O2/ZrCl4 system as a method to oxidize sulfides
efficiently to either sulfoxides or sulfones and selectively
oxidize sulfides containing other easily oxidized groups.
The route for the synthesis of sulfoxides and sulfones is
shown in Scheme 1.
Oxidation of sulfides is the most straightforward
method for the synthesis of sulfoxides and sulfones,1
some examples of which are important as commodity
chemicals and, in some cases, as pharmaceuticals.2 This
transformation has been accomplished in a variety of
ways.3–15 However, the reported methods rarely offer
the ideal combination of simplicity of method, rapid
and selective reactions, and high yields of products
and often suffer from a lack of generality and economic
applicability. On the other hand, selective oxidation of
sulfides to sulfoxides and sulfides to sulfones with the
same reagent system under adjusted reaction conditions
is an important process in synthetic organic chemistry
and only a few reports are available in the literature
for this purpose.16 As a consequence, the introduction
of new methods and/or further work on technical
improvements to overcome the limitations is still an
important experimental challenge. The chemoselective
oxidation of sulfides is also another point of interest.
During recent years, very useful procedures involving
aqueous hydrogen peroxide (H2O2) as the terminal oxi-
dant, due to the effective oxygen content, low cost,
safety in storage and operation and environmentally
friendly character of H2O2 and a Lewis acid as an acti-
vator have been developed to promote this transforma-
The applicability of the H2O2/ZrCl4 system was then
examined for the sulfoxidation of diaryl, dibenzyl, aryl
benzyl, dialkyl and cyclic sulfides in methanol at room
temperature. A ratio of 2:14:4 sulfide/H2O2/ZrCl4 was
found to be optimum for complete conversion of sulfides
to sulfoxides and the results are presented in Table 1. As
shown, all the reactions were complete within a very
short time and the sulfoxides were obtained in almost
quantitative yields as the sole oxidation products.
O
S
O
S
(i)
(ii)
R
R'
R
S
R'
R
R'
O
(1)
(2)
(3)
Scheme 1. Reagents and conditions: (i) H2O2 (14 equiv), ZrCl4
(4 equiv), CH3OH, rt; (ii) H2O2 (20 equiv), ZrCl4 (5 equiv), CH3OH,
rt.
*
Fax: +98 831 4274559; e-mail: k2005bahrami@yahoo.com
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.051

2010
K. Bahrami / Tetrahedron Letters 47 (2006) 2009–2012
Table 1. Oxidation of sulfides to sulfoxides using the H2O2 (14 equiv)/ZrCl4 (4 equiv) system
Sulfide 1
Sulfoxide 2a
Time (min)
Yieldb (%)
(C6H5)2S 1a
C6H5CH2SC6H5 1b
(C6H5CH2)2S 1c
4-O2NC6H4CH2SC6H5 1d
4-MeC6H4SCH2C6H5 1e
4-ClC6H4SCH2C6H5 1f
4-BrC6H4CH2SCH2C6H5 1g
4-BrC6H4CH2SC6H44-Me 1h
4-BrC6H4CH2SC6H44-Cl 1i
4-O2NC6H4CH2SC6H44-Cl 1j
(C6H5)2SO 2a
C6H5CH2SOC6H5 2b
(C6H5CH2)2SO 2c
4-O2NC6H4CH2SOC6H5 2d
4-MeC6H4SOCH2C6H5 2e
4-ClC6H4SOCH2C6H5 2f
4-BrC6H4CH2SOCH2C6H5 2g
4-BrC6H4CH2SOC6H44-Me 2h
4-BrC6H4CH2SOC6H44-Cl 2i
4-O2NC6H4CH2SOC6H44-Cl 2j
1
2
2
3
2
3
3
2
3
3
96
96
97
95
94
94
96
95
97
93
1k
2k
3
3
99
99
S
S
O
O
O
1l
2l
S
S
O
C6H5SMe 1m
C6H5SOMe 2m
1
1
1.5
1
1
97
95
94
95
96
94
4-MeC6H4SMe 1n
4-ClC6H4SMe 1o
C6H5SCH2CH@CH2 1p
(CH2@CHCH2)2S 1q
(n-C4H9)2S 1r
4-MeC6H4SOMe 2n
4-ClC6H4SOMe 2o
C6H5SOCH2CH@CH2 2p
(CH2@CHCH2)2SO 2q
(n-C4H9)2SO 2r
1
a All products were identified by comparison of their physical and spectral data with those of authentic samples.
b Isolated yields.
The chemoselectivity is noteworthy. Under such condi-
tions, the sulfide function was highly reactive, and vari-
ous other functional groups such as alkenes and a
ketone (Table 1, entries 1p, 1q and 1l), were tolerated.
1.4 mL) and ZrCl4 (4 mmol, 0.93 g) were added and
the mixture was stirred at room temperature for the time
indicated in Table 1. The progress of the reaction was
monitored by TLC (eluent: n-hexane/ethyl acetate:
7/3). When the starting sulfide had completely dis-
appeared, the reaction mixture was quenched by adding
water (15 mL), extracted with chloroform (4 · 10 mL)
and the extract dried with anhydrous MgSO4. The fil-
trate was evaporated and the corresponding sulfoxide
was obtained as the only product (Table 1). An identical
procedure was employed using 30% H2O2 (20 mmol,
2 mL) and ZrCl4 (5 mmol, 1.16 g) for the oxidation of
sulfides to sulfones (Table 2).
In order to demonstrate the efficiency and applicability
of the H2O2/ZrCl4 system further, the chemoselective
oxidation of sulfides to sulfones was also investigated.
The reaction conditions specified in Table 2 were opti-
mized for carrying out the reaction in methanol at room
temperature (sulfide/H2O2/ZrCl4 ratio = 2:20:5). In
practice, using a lower amount of oxidant produced a
mixture of sulfoxide and sulfone. It was found that a
wide variety of diaryl, dialkyl, dibenzyl, aryl benzyl,
alkyl aryl and cyclic sulfides were oxidized to their
corresponding sulfones in excellent yields in methanol
at room temperature. The results are summarized in
Table 2.
2.1. 4-Nitrobenzyl phenyl sulfoxide 2d
1
Mp 161–163 ꢁC; IR (KBr, cmÀ1) 1026, 1345, 1515; H
NMR (200 MHz, CDCl3): d 4.04 (d, 1H, J = 12.0 Hz),
4.24 (d, 1H, J = 12.0 Hz), 7.13 (d, 2H, J = 6.5 Hz),
7.40–7.51 (m, 5H), 8.12 (d, 2H, J = 6.5 Hz). Anal. Calcd
for C13H11NSO3: C, 59.76; H, 4.24; N, 5.36; S, 12.27.
Found: C, 59.65; H, 4.32; N, 5.25; S, 12.40.
In conclusion, ZrCl4 is an excellent Lewis acid for pro-
moting the highly chemoselective and rapid oxidation
of functionalized sulfides with 30% H2O2 under very
mild conditions. It is noteworthy that the reaction toler-
ates oxidatively sensitive functional groups and that the
sulfur atom is selectively oxidized.
2.2. Benzyl 4-bromobenzyl sulfoxide 2g
Mp 139–140 ꢁC; IR (KBr, cmÀ1) 1028; 1H NMR
(500 MHz, CDCl3): d 3.78 (d, 1H, J = 13.1 Hz), 3.89
(d, 1H, J = 13.09 Hz), 3.95 (s, 2H), 7.2 (d, 2H,
J = 8.3 Hz), 7.32–7.33 (m, 2H), 7.40–7.44 (m, 3H),
7.54 (d, 2H, J = 8.3 Hz). Anal. Calcd for C14H13SOBr:
C, 54.38; H, 4.24; S, 10.37. Found: C, 54.30; H, 4.20;
S, 10.47.
2. General procedure for the oxidation of sulfides
In a round-bottomed flask (50 mL) equipped with a
magnetic stirrer, a solution of sulfide (2 mmol) in
CH3OH (15 mL) was prepared. H2O2 (30%, 14 mmol,

K. Bahrami / Tetrahedron Letters 47 (2006) 2009–2012
2011
Table 2. Oxidation of sulfides to sulfones using the H2O2 (20 equiv)/ZrCl4 (5 equiv) system
Sulfide 1
Sulfone 3a
Time (min)
Yieldb (%)
(C6H5)2S 1a
C6H5CH2SC6H5 1b
(C6H5CH2)2S 1c
4-O2NC6H4CH2SC6H5 1d
4-MeC6H4SCH2C6H5 1e
4-ClC6H4SCH2C6H5 1f
4-BrC6H4CH2SCH2C6H5 1g
4-BrC6H4CH2SC6H44-Me 1h
4-BrC6H4CH2SC6H44-Cl 1i
4-O2NC6H4CH2SC6H44-Cl 1j
(C6H5)2SO2 3a
C6H5CH2SO2C6H5 3b
(C6H5CH2)2SO2 3c
4-O2NC6H4CH2SO2C6H5 3d
4-MeC6H4SO2CH2C6H5 3e
4-ClC6H4SO2CH2C6H5 3f
4-BrC6H4CH2SO2CH2C6H5 3g
4-BrC6H4CH2SO2C6H44-Me 3h
4-BrC6H4CH2SO2C6H44-Cl 3i
4-O2NC6H4CH2SO2C6H44-Cl 3j
1.5
2
2
3.5
2
3.5
3
2
3
4
99
98
97
99
96
95
96
95
97
99
1k
3k
2
2
99
S
S
O2
O
O
1l
3l
99
S
O2
S
C6H5SMe 1m
C6H5SO2Me 3m
1
1
2
1
1
2
97
98
95
95
98
97
4-MeC6H4SMe 1n
4-ClC6H4SMe 1o
C6H5SCH2CH@CH2 1p
(CH2@CHCH2)2S 1q
(n-C4H9)2S 1r
4-MeC6H4SO2Me 3n
4-ClC6H4SO2Me 3o
C6H5SO2CH2CH@CH2 3p
(CH2@CHCH2)2SO2 3q
(n-C4H9)2SO2 3r
a All products were identified by comparison of their physical and spectral data with those of authentic samples.
b Isolated yields.
Cohn, O., Rees, C. W., Pattenden, G., Eds.; Elsevier:
Oxford, 1995; Vol. 2, pp 144–152, pp 154–156; (b) The
Synthesis of Sulphones, Sulphoxides, and Cyclic Sulphides;
Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1994; (c)
Simpkins, N. S. In Sulphones in Organic Synthesis;
Baldwin, J. E., Magnus, P. D., Eds.; Pergamon: Oxford,
1993; pp 5–99.
2.3. 4-Nitrobenzyl phenyl sulfone 3d
Mp 204–205 ꢁC; IR (KBr, cmÀ1) 1142, 1300, 1345, 1515;
1H NMR (200 MHz, CDCl3): d 4.44 (s, 2H), 7.10 (d, 2H,
J = 6.5 Hz), 7.40–7.70 (m, 5H), 8.18 (d, 2H, J = 6.5 Hz).
Anal. Calcd for C13H11NSO4: C, 56.31; H, 3.99; N, 5.05;
S, 11.56. Found: C, 56.17; H, 4.10; N, 4.97; S, 11.70.
2. (a) Clark, E. In Kirk–Othmer Encyclopedia of Chemical
Technology, 4th ed; Kroschwitz, J. I., Howe-Grant, M.,
Eds.; Wiley: New York, 1997; Vol. 23, pp 134–146; (b)
Willer, R. In Kirk–Othmer Encyclopedia of Chemical
Technology, 4th ed; Kroschwitz, J. I., Howe-Grant, M.,
Eds.; Wiley: New York, 1997; Vol. 23, pp 217–
232.
2.4. Benzyl 4-bromobenzyl sulfone 3g
Mp 176–178 ꢁC; IR (KBr, cmÀ1) 1116, 1299; H NMR
(80 MHz, CDCl3): d 4.02 (s, 2H), 4.14 (s, 2H), 7.17–
7.60 (m, 9H). Anal. Calcd for C14H13BrSO2: C, 51.70;
H, 4.03; S, 9.86. Found: C, 51.60; H, 4.15; S, 9.90.
1
3. Chen, Y.-J.; Huang, Y.-P. Tetrahedron Lett. 2000, 41,
5233.
4. Shaabani, A.; Teimouri, M. B.; Safaei, H. R. Synth.
Commun. 2000, 30, 265.
5. Bravo, A.; Dordi, B.; Fontana, F.; Minisci, F. J. Org.
Chem. 2001, 66, 3232.
Acknowledgements
We are thankful to the Razi University Research Coun-
cil, for partial support of this work.
6. Procter, D. J. J. Chem. Soc., Perkin Trans. 1 2001, 335.
7. Batigalhia, F.; Zaldini-Hernandes, M.; Ferreira, A. G.;
Malvestiti, I.; Cass, Q. B. Tetrahedron 2001, 57, 9669.
8. Martin, S. E.; Rossi, L. I. Tetrahedron Lett. 2001, 42,
7147.
9. Xiong, Z.-X.; Huang, N.-P.; Zhong, P. Synth. Commun.
2001, 31, 245.
10. Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. J. Org.
Chem. 2002, 67, 8666.
11. Pelotier, B.; Anson, M. S.; Campbell, I. B.; Macdonald, S.
J. F.; Priem, G.; Jackson, R. F. W. Synlett 2002, 1055.
12. Kim, S. S.; Nehru, K.; Kim, S. S.; Kim, D. W.; Jung, H. C.
Synthesis 2002, 2484.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.01.051.
References and notes
13. (a) Firouzabadi, H.; Seddighi, M. Synth. Commun. 1991,
21, 211; (b) Firouzabadi, H.; Mohammadpoor-Baltork, I.
Bull. Chem. Soc. Jpn. 1992, 65, 1131; (c) Iranpoor, N.;
1. (a) Hollingworth, G. J. In Comprehensive Organic Func-
tional Group Transformations; Katritzky, A. R., Meth-

2012
K. Bahrami / Tetrahedron Letters 47 (2006) 2009–2012
Firouzabadi, H.; Pourali, A.-R. Tetrahedron 2002, 58,
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.
5179; (d) Iranpoor, N.; Firouzabadi, H.; Pourali, A.-R.
Synlett 2004, 347.
14. Kar, G.; Saikia, A. K.; Bora, U.; Dehury, S. K.;
Chaudhuri, M. K. Tetrahedron Lett. 2003, 44, 4503.
15. Xu, W. L.; Li, Y. Z.; Zhang, Q. S.; Zhu, H. S. Synthesis
2004, 227.
16. (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.;
17. Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-Q.; Noyori, R.
Tetrahedron 2001, 57, 2469.
18. Yoshihito, W.; Tatsuo, N.; Shigeru, O. Synthesis 1981,
204.