A facile and selective procedure for oxidation of sulfides to sulfoxides with molecular bromine on hydrated silica gel in dichloromethane

Article abstract of DOI:10.1055/s-1998-6097

A new method for oxidation of sulfides to sulfoxides with molecular bromine on a solid silica gel support has been developed. This procedure cleanly oxidizes sulfides to the corresponding sulfoxides in excellent yields. To our knowledge, this is the first

Full text of DOI:10.1055/s-1998-6097

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SYNTHESIS
Short Papers
1238
A Facile and Selective Procedure for Oxidation of Sulfides to Sulfoxides with Molecular
Bromine on Hydrated Silica Gel in Dichloromethane
Mohammed Hashmat Ali,* Gary J. Bohnert
Department of Chemistry, Southeast Missouri State University, One University Plaza, Cape Girardeau, Missouri 63701, USA
Fax +1(573)6512223; E-mail: c238scc@semovm.semo.edu
Received 12 July 1997; revised 3 February 1998
for non-silica gel supported reactions;3 and (3) hydrated
silica gel support eliminates laborious aqueous workup of
Abstract: A new method for oxidation of sulfides to sulfoxides
with molecular bromine on a solid silica gel support has been
developed. This procedure cleanly oxidizes sulfides to the corre-
the reaction, as the solid support, and the byproduct of the
sponding sulfoxides in excellent yields. To our knowledge, this is
oxidant are all easily removed by filtration. In addition,
bromine is an inexpensive and readily available reagent.
In this procedure, a dichloromethane solution of bromine
(5–10 mole percent excess) is added to a heterogeneous
mixture of a sulfide and hydrated silica gel (see the gener-
al procedure) in dichloromethane. The reaction mixture is
stirred at room temperature for five minutes or until the
reaction is complete (reaction time for various sulfides
listed in the Table). The reaction mixture is then filtered
and the solid is washed with dichloromethane. Removal
of solvent from the filtrate yields product. Impure prod-
ucts were purified by radial chromatography utilizing
chromatotron.
the first example of oxidation of sulfides by molecular bromine in
dichloromethane that does not require the presence of a base or
another reagent to scavenge the byproduct hydrogen bromide in
order to prevent side reactions. The reported procedure is simple,
fast, product isolation is trivial, and it produces excellent yields.
Key words: sulfides, sulfoxides, bromine, hydrated silica gel sup-
port, solid, support
The biggest disadvantage of the utilization of bromine in
the oxidation of sulfides was undesired side reactions that
often predominated over sulfoxide formation.1 Cleavage
of the C–S bond and bromination of the sulfide substrate
at various positions are two unwanted reactions observed
in this oxidation process. Hydrogen bromide is considered
responsible for these unwanted side reactions. Procedures
that produced limited success in preventing these side re-
actions utilized either a complex of bromine and an amine
in aqueous acetic acid media, or are carried out in a bipha-
sic medium (CH2Cl2/H2O) using potassium hydrogen car-
bonate or pyridine as the hydrogen bromide acceptor.2
Another procedure involved treatment of the reaction
mixture with hexabutyldistannoxane in order to suppress
the formation of sulfones.3 Although these reactions have
some success in preventing undesired side reactions, they
are less attractive because they require additional steps in
the preparation of the bromine–amine complexes or uti-
lize a toxic reagent. In addition, reactions in aqueous me-
dia produce low product yields. This demonstrates the
need for a simple and efficient method for conversion of
sulfides to the corresponding sulfoxides with molecular
bromine.
We believe this oxidation process follows the mechanism
previously proposed in the literature.1
In this reaction, hydrated silica gel also plays the follow-
ing two very important roles. (i) The water present in the
hydrated silica gel affects the hydrolysis of the sulfonium
bromide 2A and/or sulfurane 2B intermediate to the sulf-
oxide. (ii) Silica gel acts as a hydrogen bromide acceptor.
Hydrogen bromide is absorbed on the silica gel and as a
result side reactions, which are believed to be initiated by
free hydrogen bromide, are minimized.
We have recently demonstrated that sulfides can be oxi-
dized to sulfoxides or sulfones on hydrated silica gel em-
ploying magnesium monoperoxyphthalate (MMPP) as the
oxidant in dichloromethane solvent.4 In this paper, we
demonstrate that bromine can also be utilized as the oxi-
dant for conversion of sulfides to the corresponding sul-
foxides on hydrated silica gel utilizing dichloromethane
as the solvent. Use of hydrated silica gel as solid support
for this oxidation reaction offers many advantages. These
include: (1) dichloromethane can be utilized as the reac-
tion media instead of water which was traditionally em-
ployed in the oxidation reactions with bromine; (2) hy-
drated silica gel activates the oxidation reaction by dis-
persing the oxidant, which is reflected in the very short
reaction time for oxidation of sulfides with bromine sup-
ported on silica gel compared to the longer reaction time
This new method provides a convenient, fast, and eco-
nomic way to oxidize sulfides to the corresponding sul-
foxides. The most important feature of this procedure, un-
like others, is that the presence of a base or another re-
agent is not required to prevent side reactions.
Overoxidation of sulfides to sulfones can easily be pre-
vented by not employing a large excess of bromine in the
reaction.5
The selectivity of this procedure is excellent. Oxidation of
sulfides to the corresponding sulfoxides can tolerate the

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SYNTHESIS
September 1998
1239
Table. Oxidation of Sulfides to Sulfoxides
The results of oxidation of methyl 4-methylphenyl sulfide
(1h), 4-methoxyphenyl methyl sulfide (1i), and methyl 4-
nitrophenyl sulfide (1j), clearly demonstrate that a deacti-
vating group at the 4-position of the aromatic ring makes
the sulfides less reactive whereas an activating group at
this position makes it more reactive towards the oxidation
reaction. This observation is consistent with the reported
results on oxidation reactions of sulfides with electro-
philic reagents.6
1–3 Sulfide 1
Sulfoxide 3
Time Yield
(min.)a (%)b
a
b
c
10
40
50
100
100
100
All reaction mixtures were magnetically stirred. CH2Cl2 was used as
received from the supplier without any further purification. Sulfides
1a–f, 1h–j and 1n were purchased from Aldrich Chemical Company,
USA. and sulfides 1l,m were purchased from Lancaster Synthesis
Inc. The above sulfides were used as they were received without fur-
ther purification. Sulfides 1g, and 1k were prepared according to the
procedure described in ref 7. Reactions reported in the Table em-
ployed a slight excess of Br2 (~10 mol% excess). All products are
known compounds and were identified by comparison of the NMR
and IR data with those reported in the literature or of authentic com-
mercial products. Br2 was purchased from Aldrich Chemical Compa-
ny, USA. The silica gel used in the oxidation reactions as solid sup-
port was MN-Kieselgel 60 (0.04–0.063 mm mesh size) supplied by
Fisher Scientific. 1H NMR spectra were recorded on a Hitachi–Perkin
Elmer R24A 60 MHz NMR instrument. Samples for NMR were dis-
solved in CDCl3. 1H chemical shifts are expressed as ppm relative to
TMS. IR spectra were recorded on an Analect RFX-30 FT-IR instru-
ment and are reported in wavenumbers (cm–1). Chromatographic sep-
arations were carried out by preparative centrifugal TLC with silica
gel (Merck #7749) on a Chromatotron Model 7924T. Analytical TLC
was done on precoated silica gel plates with 254 nm fluorescent indi-
cator (Merck #5715) and developed in the indicated solvent systems.
Compounds were visualized under a UV lamp and/or by staining ei-
ther with p-anisaldehyde/H2SO4 or phosphomolybdic acid.
d
50
60
100
e
f
100
87
5c
g
120
15
10
40
40
80
h
i
95
100
97
j
k
90
l
15
5
98
Oxidation of Dibutyl Sulfide (1a) to Dibutyl Sulfoxide (3a); Typi-
cal Procedure:
m
100
Dry silica gel (5 g) was placed in a 100-mL round bottom flask con-
taining a magnetic stirring bar and a loosely fitted rubber septum. Wa-
ter (2.5 g) was added to the vigorously stirred silica gel. After com-
plete addition of the water, stirring continued until a free flowing
powder was obtained (5 min). CH2Cl2 (25 mL) was added to the flask.
A solution of dibutyl sulfide (1a) (384 mg, 2.62 mmol) in CH2Cl2
(5 mL) was added to the stirred heterogeneous mixture. A solution of
Br2 (0.14 mL, 2.72 mmol) in CH2Cl2 (2 mL) was added dropwise
from a syringe to the mixture. The color of the Br2 disappeared in-
stantly. The mixture was stirred at r.t. for 10 min. During this period
complete disappearance of the dibutyl sulfide was confirmed by TLC
(EtOAc/hexane 1:1, p-anisaldehyde/H2SO4). The mixture was then
filtered through a sintered glass funnel, the solid residue was washed
with CH2Cl2 (75 mL) and the washings were added to the filtrate.
Removal of solvent from the CH2Cl2 solution under vacuum pro-
duced a colorless thick oil. Radial chromatography (EtOAc/hexane
1:1) of the crude product produced dibutyl sulfoxide (3a) as a color-
less thick oil (426 mg, 100%).
n
120
60d
a All reaction mixtures stirred at r.t. for at least 5 min.
b Isolated yield.
c Reaction temperature 0°C.
d Remaining unreacted phenyl sulfide recovered.
presence of alkene, ketone, ester, nitro, and ether groups.
Oxidation of ethyl 2-(phenylthio)propanoate (1g), methyl
4-methylphenyl sulfide (1h), 2-(phenylthio)acetophenone
(1k) and benzyl methyl sulfide (1m) to the corresponding
sulfoxides without any complication from bromination at
the α-position is also notable. Until now, undesired
α-bromination was the biggest disadvantage for employ-
ment of molecular bromine in the oxidation of sulfides.1
Steric bulkiness of the sulfide has no detrimental effects
on the efficacy of this procedure except, that as expected,
oxidation of sterically hindered sulfides proceeds some-
what slowly compared to unhindered sulfides. For exam-
ple, diphenyl sulfide (1n) requires a longer reaction time
and produces yields which are lower than the other sul-
fides studied. This is not surprising since the reported ox-
idation of diphenyl sulfide with a complex of molecular
bromine and hexabutyldistannoxane gave poor results.3
Dibutyl Sulfoxide (3a):8
1H NMR: δ = 0.974 (t, 6H, J = 7.0 Hz), 1.20–1.8 (m, 8H), 2.70 (t, J =
7.0 Hz, 4H).
IR: ν = 1027, 1280, 1406, 1425, 1469, 2887, 2942, 2964 cm–1.
Di-tert-butyl Sulfoxide (3b):9
1H NMR: δ = 1.35 (s).
IR: ν = 816, 1027, 1035, 1180, 1236, 1376, 1485, 2876, 2931,
2963 cm–1.

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SYNTHESIS
Short Papers
1240
1-Oxotetrahydrothiophene (3c):8
Benzyl Methyl Sulfoxide (3m):13
1H NMR: δ = 1.80–2.50 (m, 4H), 2.55–2.90 (m, 4H).
IR: ν = 1025, 1215, 1235, 1616, 1771, 1725, 2887, 2952 cm–1.
1H NMR: δ = 2.46 (s, 3H), 4.00 (s, 2H), 7.10–7.50 (m, 5H).
IR: ν = 1010, 1286, 1370, 1455, 1500, 3050 cm–1.
Diphenyl Sulfoxide (3n):12
4-Oxo-1,4-thioxane (3d):10
1H NMR: δ = 7.40–7.64 (m).
1H NMR: δ = 2.40–3.10 (m, 4H), 3.50–4.50 (m, 4H).
IR: ν = 1005, 1028, 1071, 1114, 1224, 1289, 1398, 1409, 1475, 1660,
2871, 2936, 2980 cm–1.
IR: ν = 708, 766, 1049, 1104, 1453, 1485, 3067 cm–1.
Methyl Phenyl Sulfoxide (3e):8
Author M. H. A. is grateful to the Grants and Research Funding
Committee (GRFC) at the Southeast Missouri State University for
the financial support.
1H NMR: δ = 2.68 (s, 3H), 7.40–7.70 (m, 5H).
IR: ν = 692, 754, 954, 1046, 1092, 1415, 1446, 1477, 2915, 3000,
3062 cm–1.
(1) Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. In Synthesis of
Sulphones, Sulphoxides and Cyclic Sulphides; Patai, S.; Rappo-
port, Z., Eds.; Wiley: New York, 1994.
(2) Oae, S.; Onishi, Y.; Kozuka, S.; Tagaki, W. Bull. Chem. Soc.
Jpn. 1966, 39, 364.
Drabowicz, J.; Midura, W.; Mikolajczyk, M. Synthesis 1979, 39.
(3) Ueno, Y.; Inoue, T.; Okawara, M. Tetrahedron Lett. 1977, 2413.
(4) Ali, M. H.; Stevens, W. C. Synthesis 1997, 764.
Ali, M. H.; Bohnert, G. J. (submitted to Synth. Commun.)
(5) We have found that in the presence of two or more mole equi-
valents of bromine, sulfides are oxidized to the sulfones in ex-
cellent yields. A study to explore this route to produce sulfones
is in progress.
Allyl Methyl Sulfoxide (3f):11
1H NMR: δ = 2.05 (s, 3H), 3.48 (d, 2H), 5.10–6.20 (m, 3H).
IR: ν = 743, 951, 1049, 1431, 1649, 2925, 3001, 3088 cm–1.
Ethyl 2-(Phenylsulfinyl)propanoate (3g):12
1H NMR: δ = 1.00–1.50 (m, 6H), 3.40– 4.50 (m, 3H), 7.45 (m, 5H).
IR: ν = 701, 759, 1060, 1094, 1180, 1232, 1325, 1385, 1464, 1741,
2873, 2920, 2954, 2988, 3070 cm–1.
Methyl 4-Methylphenyl Sulfoxide (3h):13
1H NMR: δ = 2.40 (s, 3H), 2.70 (s, 3H), 7.30 (d, J = 8.5 Hz, 2H), 7.50
(d, J = 8.5 Hz, 2H).
IR: ν = 820, 962, 1049, 1093, 1420, 1507, 1605, 2882, 2936, 3000,
(6) Hirano, M.; Tomaru,; Morimoto, T. Bull. Chem. Soc. Jpn. 1991,
64, 3752 and references therein.
3056 cm–1.
(7) A mixture of PhSH, Et3N, an appropriate chloro- or bromo-
compound and Et2O was stirred at r.t. overnight. The mixture,
which produces copious amount of Et3NHX (X = Cl or Br), was
then filtered. The filtrate was washed with water and brine suc-
cessively, and then dried (anhyd MgSO4). The drying agent was
removed by filtration, filtrate was concentrated under vacuum
and the residue was purified by recrystallization or by flash
chromatography as appropriate.
(8) This product was identified by comparing the NMR and IR data
with those of the commercially available authentic sample.
(9) Drabowicz, J.; Lyzwa, P. J.; Popielarczyk, M.; Mikolajczyk, M.
Synthesis 1990, 937.
(10) Szarek, W. A.; Vyas, D. M.; Sepulchre, A-M.; Gero, S. D.; Lu-
kacs, G. Can. J. Chem. 1974, 52, 2041.
(11) Kimmelma, R. Acta Chem. Scand. 1993, 47, 706.
(12) Akemi, T.; Ono, Y.; Chiba, J.; Sugihara, C. K. Chem. Pharm.
Bull. 1996, 44, 703.
4-Methoxyphenyl Methyl Sulfoxide (3i):13
1H NMR: δ = 2.60 (s, 3H), 3.80 (s, 3H), 7.00 (d, J = 9 Hz, 2H), 7.50
(d, J = 9 Hz, 2H).
IR: ν = 820, 957, 986, 1016, 1103, 1180, 1267, 1311, 1474, 1507,
1605, 2860, 2915, 2969, 2990, 3078, 3100 cm–1.
Methyl 4-Nitrophenyl Sulfoxide (3j):14
1H NMR: δ = 2.80 (s, 3H), 7.75 (d, J = 9 Hz, 2H), 8.30 (d, J = 9 Hz,
2H).
IR: ν = 748, 863, 967, 1048, 1094, 1348, 1533, 2868, 2925, 3029,
3110 cm–1.
2-(Phenylsulfinyl)acetophenone (3k):15
1H NMR: δ = 4.10–4.60 (m, 2H), 7.20–7.90 (m, 10H).
IR: ν = 692, 754, 1000, 1046, 1092, 1200, 1277, 1446, 1468, 1587,
1600, 1677, 2908, 2954, 3000, 3062 cm–1.
(13) Brunel, J-M.; Diter, P.; Duetsch, M.; Kagan, H. B. J. Org.
Chem. 1995, 60, 8086.
(14) Yang, R-Y.; Dai, L-X. Synth. Commun. 1994, 24, 2229.
(15) Solladie-Cavello, A.; Suffert, J.; Adib, A.; Solladie, G. Tetrahe-
dron Lett. 1990, 31, 6649.
Ethyl Phenyl Sulfoxide (3l):16
1H NMR: δ = 1.10 (t, J = 8 Hz, 3H), 2.80 (dq, J = 8 Hz, 2H), 7.50 (m,
5H).
IR: ν = 692, 749, 965, 1022, 1040, 1078, 1412, 1446, 1488, 2954,
(16) Hojo, M.; Masuda, R.; Saeki, T.; Fujimori, K.; Tsutsumi, S.
Synthesis 1977, 789.
2976, 3056 cm–1.