A clean, mild, and selective oxidation of sulfides to sulfoxides using NaClO/H2SO4 in Aqueous Media

Article abstract of DOI:10.1080/10426500802529226

A range of sulfides can be selectively oxidized to the corresponding sulfoxides in good yields using NaClO/H₂SO₄ in both water and 50:50 water:EtOH as solvent. Two new compounds are reported that show a diastereoselective oxidation in 2-phenylthioalcohols with possible neighboring hydroxyl group participation with a logic proposed mechanism. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500802529226

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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A Clean, Mild, and Selective
Oxidation of Sulfides to
Sulfoxides Using NaClO/H SO
2
4
in Aqueous Media
a
a
Ali Amoozadeh & Firouzeh Nemati
a
Department of Chemistry, Faculty of Science ,
Semnan University , Semnan, Iran
Published online: 21 Sep 2009.
To cite this article: Ali Amoozadeh & Firouzeh Nemati (2009) A Clean, Mild, and
Selective Oxidation of Sulfides to Sulfoxides Using NaClO/H SO in Aqueous Media,
2
4
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:10, 2569-2575, DOI:
0.1080/10426500802529226
1
To link to this article: http://dx.doi.org/10.1080/10426500802529226
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Phosphorus, Sulfur, and Silicon, 184:2569–2575, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802529226
A Clean, Mild, and Selective Oxidation of Sulfides to
Sulfoxides Using NaClO/H SO in Aqueous Media
2
4
Ali Amoozadeh and Firouzeh Nemati
Department of Chemistry, Faculty of Science, Semnan University,
Semnan, Iran
A range of sulfides can be selectively oxidized to the corresponding sulfoxides in
good yields using NaClO/H2SO4 in both water and 50:50 water:EtOH as solvent.
Two new compounds are reported that show a diastereoselective oxidation in 2-
phenylthioalcohols with possible neighboring hydroxyl group participation with a
logic proposed mechanism.
Keywords Green chemistry; oxidation; sodium hypochlorite; sulfide; sulfoxide
INTRODUCTION
The oxidation of sulfides is the major method for the synthesis of sul-
foxides, which are versatile intermediates in organic synthesis and are
1
2
usable for C–C bond formation, functional group transformations,
and are useful for the preparation of biologically and medically im-
3
portant compounds. Sulfoxides could easily be converted to carboxylic
4
acid derivatives by Pummerer rearrangement.
Although many reagents are available for the oxidation of sulfides to
5
sulfoxides, catalytic processes with environmentally benign oxidants
have become increasingly important. Recently, hydrogen peroxide has
been a very attractive “green oxidant,” offering such advantages as
it is inexpensive, environmentally benign, and readily available, and
6
produces only water as a byproduct. But a frequent drawback of these
convenient methods is often the use of chlorohydrocarbon solvents or
7
anhydrous H2O2 in ethanol, and the over-oxidation to sulfones as side
products.
Received 6 June 2008; accepted 18 September 2008.
We thank the Department of Chemistry of Semnan University for supporting this
work.
Address correspondence to Ali Amoozadeh, Department of Chemistry, Faculty of Sci-
ence, Semnan University, Semnan, Iran. E-mail: aliamoozadeh@yahoo.com
2569

2570
A. Amoozadeh and F. Nemati
It is further known that the hypochlorous acid oxidation of certain
8
sulfides leads to corresponding sulfoxides, most probably via the cor-
responding chlorosulfonium ion as demonstrated by Johnson and Mc-
9
Cants in the oxidation of thianes with tert-butyl hypochlorite. These
types of oxidations are very pH- and solvent-dependent.
RESULTS AND DISCUSSION
In this article, we wish to report an efficient protocol in which NaClO
in acid sulfuric media has been used as the oxidizing agent in water
and a mixture of H2O:EtOH (50:50) for the chemoselective oxidation
of sulfides to their sulfoxides in high chemical yield and short reaction
times.
The oxidation of sulfides in water or water/EtOH is desirable, since
using water and EtOH instead of an organic solvent has become more
important due to environmental consideration in recent years. It is
very important to note that the nature and amount of added sulfuric
acid is very important. While hydrochloric acid initiated the oxidation,
the concentration of the desired sulfoxides reached a maximum and
then began decreasing drastically as monitored by TLC. This is most
probably due to a reaction analogous to the known reductive effect of
hydrogen bromide on sulfoxides, which takes place under the present
1
0
conditions (Scheme 1).
In a typical general experimental procedure, a solution of sulfide (1
mmol) and 1 mmol NaClO in a 50:50 mixture of H2O:EtOH in sulfuric
acid media was stirred for a period of time, and this resulted in the for-
mation of the corresponding sulfoxides without any over-oxidation and
with good to excellent yields. In the case of water as solvent, vigorous
stirring is necessary because the reaction takes place in the surface
of suspension or emulsion sulfide in water. To study the scope of this
procedure, a series of various substituted sulfides including alkyl aryl
sulfides and dialkyl sulfides was reacted according to optimized reac-
tion conditions. The results are summarized in Table I.
SCHEME 1 Reduction of sulfoxides by hydrobromic acid.

Oxidation of Sulfides to Sulfoxides
2571
TABLE I Oxidation Sulfides to Sulfoxides by NaClO in Water and a
50:50 Mixture of H
2
O/Ethanol
a
Yield(%) In
a
Time Yield (%) In
50:50
Entry
R1
R2
(min)
water
Water/EtOH
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Et
Et
n-Pr
Ph
Me
Et
Ph
Bn
Et
Me
n-Pr
45
35
50
60
50
55
60
30
62
70
75
78
70
60
65
73
75
84
93
95
85
72
78
82
9b
Ph
Ph
90
70
85c
1
0b
90
72
85c
aIsolated yield.
b
The starting material was prepared according to ref. no.[14].
c
Only one diastereoisomer was observed.
The process is devoid of sulfone formation, a byproduct common
to most other peroxide-based oxidations. These oxidations exhibited
striking solvent effects. We found that reaction rates were very slow
in chloroform and dichloromethane, but increased dramatically in the
H2O/EtOH mixture. Furthermore the nature and the amount of acid
are very important.
The most stable conformations of protected 2-phenylthio-3-
aminocyclohexanols (Table I, entries 9 and 10), using AM1 calculation,
1
1–13
are shown in Figure 1. Based on these results and on the literature,

2572
A. Amoozadeh and F. Nemati
FIGURE 1 The most stable calculated conformations of (a) N-(3-hydroxy-5-
isopropyl-2-(phenylthio)cyclohexyl)-3-methoxybenzamide and (b) tert-butyl 3-
hydroxy-5-isopropyl-2-(phenylthio)cyclohexylcarbamate.
a neighboring hydroxyl group effect could be considered. We have pro-
posed a mechanism, shown in Scheme 2.
In conclusion, the results reported in this article clearly indicate that
by using 1 mol of NaClO, it is possible to obtain a mild and chemoselec-
tive synthesis of sulfoxides from both aromatic and aliphatic sulfides.
The procedure is run in a safe solvent. Furthermore, appropriate re-
action times are needed to obtain a high yield of sulfoxides. Last, this
oxidation shows a big hydroxyl neighboring group participation and
finally a logic mechanism are proposed.
EXPERIMENTAL
The IR spectra were taken on a Perkin-Elmer, model 783 spectropho-
tometer. The NMR spectra have been recorded by a Bruker AMX-300
(
300 MHz) spectrometer. The chemical shifts are expressed in parts
per million (ppm), and tetramethylsilane (TMS) was used as internal
reference. The mass spectra (MS) were taken by an AEI MS-902 model.
General Procedure for the Synthesis of Sulfoxides
A solution of sulfide (1 mmol) and diluted NaClO (1 mmol, 1.25 mL)
(5.84% w/v) in a mixture of H2O/EtOH (50:50) (10 mL) and H2SO4 (10

Oxidation of Sulfides to Sulfoxides
2573
SCHEME 2 Proposed mechanism for stereoselective oxidation of protected
-phenylthio-3-aminocyyclohexanol (Table I, entries 9 and 10).
2

2574
A. Amoozadeh and F. Nemati
meq.) was stirred vigorously for appropriate time (30–90 min) (TLC
follow-up). The organic products were extracted by diethyl ether (4 ×
5
mL). The ether layer was washed by 2 mL of water and dried over
MgSO4. The organic solvent was removed under vacuum. The residue
was purified by recrystallization in an appropriate solvent. The sulfox-
ide from entry 9 was separated and purified by flash chromatography
as oily product.
1
Known compounds were identified by IR and H NMR spectral data.
N-(3-Hydroxy-5-isopropyl-2-(phenylsulfinyl)cyclohexyl)-3-
methoxybenzamide
1H NMR (300 MHz, CDCl3): δ 7.70 (m, 2H), 7.20 (m, 6H), 7.00 (m,
1
1
(
H), 6.10 (d, J = 12 Hz, 1H), 4.65 (m, 1H), 4.20 (m, 1H), 4.00 (m,
H), 3.80 (s, OCH3), 2.50 (broad, 1H), 1.90 (m, 2H), 1.60 (m, 2H), 1.30
1
3
m, 2H), and 1.00 (dd, J = 17, 6 Hz, 2CH3) ppm. C NMR (75 MHz,
CDCl3): δ 166.9 159.8, 135.9, 135.2, 131.0, 130.2, 129.2, 126.8, 118.5,
17.7, 112.4 67.6 66.2, 56.6, 51.5, 37.9, 34.5, 32.1, 28.3, 19.9, 19.3. IR
1
(
−1
NaCl): v max/cm 3460, 2970, 2895, 1700, 1590, 1525, 1490, 1445,
1
345, 1295, 1245, 1140, 1090, 1055, 910, 745, 695. m/z = 416 (MH+),
Calculated: 416.18956, Obtained: 416.18954.
tert-Butyl 3-hydroxy-5-isopropyl-2-(phenylsulfinyl)
cyclohexylcarbamate
1
H NMR (300 MHz, CDCl3): δ 7.75 (dd, J = 15 and 7 Hz, 2H), 7.50
(
(
(
m, 3H), 4.60 (s, broad, 1H), 4.20 (m, 2H), 3.20 (s, broad, 1 H), 1.90
d, J = 13 Hz, 1H), 1.70 (m, 2H), 1.50 (m, 3H), 1.35 (s, 9H), and 0.90
1
3
d, J = 9 Hz, 2CH3). C NMR (75 MHz, CDCl3): δ 155.0, 135.6, 132.0,
1
1
1
3
30.0, 129.1, 79.0, 67.1, 64.0, 52.0, 34.6, 32.1, 28.5, 28.3, 19.8, and
−1
9.4. IR (NaCl): v max/cm 3500, 3000, 2870, 1690, 1580, 1480, 1450,
435,1360, 1285, 1250, 1160, 1105, 1085, 1055, 920, 770, 680. m/z =
82 (MH+), Calculated: 382.20521, Obtained: 382.20518.
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(