A selective solid state oxidation of sulfides and thiols with benzyltriphenylphosphonium peroxymonosulfate

Article abstract of DOI:10.1080/10426500214100

Benzyltriphenylphosphonium peroxymonosulfate 1 could be used for oxidation of sulfides 2 and thiols 4 to their corresponding sulfoxides 3 and disulfides 5 under solid-phase conditions.

Full text of DOI:10.1080/10426500214100

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Phosphorus, Sulfur, and Silicon and the Related
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A Selective Solid State Oxidation of Sulfides and Thiols
with Benzyltriphenylphosphonium Peroxymonosulfate
A. R. Hajipour a , S. E. Mallakpour a & H. Adibi a
a Pharmaceutical Research Laboratory, College of Chemistry , Isfahan University of
Technology , Isfahan, Iran
Published online: 27 Oct 2010.
To cite this article: A. R. Hajipour , S. E. Mallakpour & H. Adibi (2002) A Selective Solid State Oxidation of Sulfides and Thiols
with Benzyltriphenylphosphonium Peroxymonosulfate, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:10,
2277-2284, DOI: 10.1080/10426500214100
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2277–2284
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Copyright 2002 Taylor & Francis
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DOI: 10.1080/10426500290106077
A SELECTIVE SOLID STATE OXIDATION OF
SULFIDES AND THIOLS WITH
BENZYLTRIPHENYLPHOSPHONIUM
PEROXYMONOSULFATE
A. R. Hajipour, S. E. Mallakpour, and H. Adibi
Pharmaceutical Research Laboratory, College of Chemistry,
Isfahan University of Technology, Isfahan, Iran
(Received July 23, 2001; accepted November 8, 2001)
Benzyltriphenylphosphonium peroxymonosulfate 1 could be used for
oxidation of sulfides 2 and thiols 4 to their corresponding sulfoxides 3
and disulfides 5 under solid-phase conditions.
Keywords: Benzyltriphenylphosphonium peroxymonosulfate; disul-
fides; oxidation; sulfides; sulfoxides; thiols
INTRODUCTION
Sulfoxides play an important role in organic chemistry.1 They have been
utilized extensively in carbon-carbon bond formation reactions.2 Oxida-
tion of sulfides is a very useful route for preparation of sulfoxides. Sev-
18
eral methods are available for conversion of sulfides to sulfoxides.3
However, some of the existing methods which have been reported,
use expensive, toxic or rare oxidizing reagents that are difficult to
10,16a
prepare.3
Many of these procedures also suffer from poor selec-
tivity. Therefore, there is a need for a simple, less expensive, and safer
method for conversion of sulfides to sulfoxides.
Disulfide bond formation is important in organic synthesis in biolog-
ically active molecules and for protein stabilization and in peptides.19
There are several various methods11,16,20 for the coupling of thiols but
most of the reagents involve metal ions and solvents that are toxic in
The authors are thankful of the Isfahan University of Technology (IUT), IR Iran for
financial support.
Address correspondence to S. E. Mallakpour, Pharmaceutical Research Laboratory,
College of Chemistry, Mutah University, Isfahan University of Technology, Isfahan
84156, Iran. E-mail: mallakpour@cc.iut.ac.ir
2277

2278
A. R. Hajipour et al.
nature. Recently, various methods have been reported for this transfor-
mation in dry media.21
Oxone (2KHSO5.KHSO4.K2SO4) is a strong, inexpensive, water-
soluble, and versatile oxidizing agent that is commercially available. It
has some disadvantages: It is insoluble in organic solvents and buffer-
ing is needed due to its acidity.
In recent years, there has been an increasing interest on reactions
that employ environmentally friendly reagents or proceed in the ab-
sence of solvents.22 Because of our interest in development of solvent-
free reactions,23 we now report on benzyltriphenylphosphonium perox-
ymonosulfate 1 as a mild and selective oxidizing reagent for oxidation of
sulfides 2 and thiols 4 to their corresponding sulfoxides 3 and disulfides
5 respectively under solvent-free conditions. This reagent is readily
prepared by reaction of an aqueous solution of Oxone with an aque-
ous solution of benzyltriphenylphosphonium chloride.24 Filtration and
drying of the precipitates resulted in a white powder, which could be
stored for months without losing its oxidizing ability. The amounts of
HSO5 in this reagent have been determined by an iodometric titra-
tion method.25 The measurements are consistent with almost 99% by
weight of active oxidizing agent. Unlike Oxone, this reagent is readily
soluble in various organic solvents such as methylene chloride, chloro-
form, acetone, and acetonitrile and insoluble in non-polar solvents such
as carbon tetrachloride, n-hexane, and ether. Very recently, we have re-
ported the synthetic utility of PhCH2Ph3P+HSO5 1 for some organic
transformations.24
RESULTS AND DISCUSSION
At first, the effects of the amount of the oxidant 1 were examined with
methyl phenyl sulfide as the substrate (1 mmol) under solvent-free con-
ditions without catalyst. The results are summarized in Table I. The
optimum ratio of sulfide to oxidant 1 (1:1.5) is found to be ideal for com-
plete conversion of sulfides 2 to sulfoxides 3 while the reaction remains
TABLE I Oxidation of Methyl Phenyl Sulfide with Different
Amounts of Reagent 1 under Solvent-Free Conditionsa
Entry
Substrate/Oxidant (mmol)
Time (min)
Yield (%)
1
2
3
4
1/1
20
20
15
10
60
70
85
1/1.2
1/1.3
1/1.5
100
aMonitored by TLC analysis.

Solid State Oxidation
2279
TABLE II Oxidation of Sulfides 2 to Sulfoxides 3 with Reagent 1 under
Solvent-Free Conditionsa,b
Entry
R1
R2
Me
n-Bu
PhCH2
Me
n-Bu
PhCH2
Me
Time (min)
Yield (%)c
1
2
3
4
5
6
7
8
9d
Ph
Ph
Ph
10
20
25
15
25
30
10
20
35
98
88
85
92
90
70
86
89
79
PhCH2
PhCH2
PhCH2
4-MeC6H4
4-ClC6H4
C4H9
Me
C4H9
aConfirmed by comparison with authentic samples.3–18
bSubstrate/oxidant (1:1.5).
cYield of isolated pure products.
dSubstrate/oxidant (1:2).
incomplete with lesser amounts for example 1:1 and 1:1.2. By using
this oxidation system, a wide variety of alkyl aryl, dialkyl, and diaryl
sulfides 2 were transformed to their corresponding sulfoxides 3 in high
yields within short reaction periods (Table II and Scheme 1). In this
method, oxidation of a sulfide is achieved by grinding a mixture of a sul-
fide and the reagent 1 in a mortar under solvent-free condition at room
temperature. The reaction time is usually between 10 and 40 min. The
sulfoxides are isolated by washing the reaction mixture with solvent
followed by filtering the mixture. Evaporation of filtrate under vacuum
often produces pure sulfoxide. Overoxidation is not a problem in our
method. This method offers a simple, general, selective, and highly-
efficient route for converting sulfides to the corresponding sulfoxides.
SCHEME 1
Benzyltriphenylphosphonium peroxymonosulfate 1 was also used
to transform thiols 4 to disulfides 5 under solvent-free conditions at
room temperature. A variety of thiols, aromatic and heterocyclic, are
converted into symmetrical disulfides 5 on simple admixing with the
reagent 1. The process in its entirety involves grinding the thiol 4 with
reagent 1 in an ambient air atmosphere. In most cases investigated,

2280
A. R. Hajipour et al.
TABLE III Oxidative Coupling of Thiols 4 to Disulfides 5 with
Reagent 1 under Solvent-Free Conditionsa,b
Entry
Thiol
Time (min)
5
Yield (%)c
1
98
2
10
10
20
25
25
40
95
98
90
88
80
80
3
4
5d
6d
7d
CH3(CH2)3SH
aConfirmed by comparison with authentic samples.11,16,20,21
bSubstrate/oxidant (1:1).
cYield of isolated pure products.
dSubstrate/oxidant (1:2).
the optimum mole ratio between the thiol and the oxidant is found to
be 1:1, which produces pure disulfides 5 in high yields (Table III and
Scheme 2). The fused ring heterocyclic (Table III, entry 7) and alkyl
thiols (Table III, entries 5, 6) afforded only traces of disulfides 5 even
after 2 h under these conditions. These reactions could be completed,
however, by increasing the oxidant/thiol ratio (Table III). In addi-
tion from economical and environmental points of view, the presented
solvent-free oxidation by reagent 1 can be compared by other methods in
the literature in terms of the reaction time, the yields of the disulfides,
mild reaction conditions and the amount of the oxidant.21
SCHEME 2
In order to evaluate the selectivity of reagent 1, the competitive re-
actions shown in Eq. 1–3 were carried out. When an equimolar amount

Solid State Oxidation
2281
of thioanisole (1 mmol) and dibenzyl sulfide (1 mmol) was treated with
1.5 molar ratio of reagent 1, only thioanisole was selectively oxidized to
methyl phenyl sulfoxide (Eq. 1).Treatment of benzyl alcohol (1 mmol)
with 1.5 molar ratio of reagent 1 in the presence of an equimolar amount
of thioanisole for 10 min, led to exclusive oxidation of benzyl alcohol to
benzaldehyde (Eq. 2). We also tried the competitive reaction between
thioanisole (1 mmol) and thiophenol (1 mmol) with reagent 1 (1 mmol),
and observed that only thiophenol was selectively oxidized to diphenyl
disulfide (Eq. 3).
O
O
||
||
1
PhSMe + PhCH2SCH2Ph
PhSMe + PhCH2OH
PhSMe + PhSH
> PhSMe + PhCH2SCH2Ph (1)
30 min
99%
0%
O
||
1
> PhSMe + PhCHO
(2)
(3)
10 min
0%
98%
O
||
1
> PhSMe + PhSSPh
10 min
0%
98%
In order to show the strong and weak points of our method, we have
compared the results of oxidation of thioanisole and thiophenol by our
method with some of those reported in the literature under solvent-free
conditions (Table IV).
TABLE IV Comparison of Oxidation of Thioanisole and Thiophenol by
Our Method with Some of Those Reported in the Literature under
Solvent-Free Conditions
Reagent (Substrate/oxidant)
Substrate
Time (min)/Yield (%)
MnO2/H2SO4/SiO2/Neat (1:2)16c
NaIO4/SiO2/MW (1:1.7)13
PhSMe
PhSMe
PhSMe
PhSMe
PhSH
PhSH
PhSH
PhSH
PhSH
60/80
2/80
75/92
10/98
0.5/98
6/97
6/97
10/79
5/98
Fe(NO3)3.9H2O/Neat (1:2)16a
PhCH2Ph3PHSO5 (1:1.5)
NH4NO3/Clay/MW (1:3)21a
Active MnO2/Neat (1:1)22d
BaMnO4/Neat (1:1)22d
(NH4)2S2O8/Grinding (1:1.1)21b
PhCH2Ph3PHSO5/Grinding (1:1)

2282
A. R. Hajipour et al.
In conclusion, this new method for converting sulfides and thiols
to their corresponding sulfoxides and disulfides offers the following
advantages: (1) the reagent 1 is a cheap, selective and safe oxidant;
(2) the procedure is simple and occurs under solvent-free condition;
(3) the yield of sulfoxide and disulfide is high; and (4) the cost of the
solvent has been eliminated.
EXPERIMENTAL
General
Yields refer to isolated pure products. The oxidation products were char-
1
acterized by comparison of their spectral (IR, H-NMR) and physical
data with the authentic samples.3 21 All 1H-NMR spectra were recorded
at 90 MHz in CDCl3 relative to TMS (0.00 ppm) and IR spectra were
recorded on Shimadzu 435 IR spectrometer. All reactions were carried
out under solvent-free conditions. The reagent 1 was prepared accord-
ing to our previously reported procedures.24
Oxidation of Sulfides 2 to Sulfoxides 3 with Reagent 1
under Solvent-Free Conditions
Typical Procedure
Thioanisole (1 mmol, 0.124 g) was added to 1 (1.5 mmol, 0.7 g), and
the mixture was ground with a pestle in a mortar until TLC showed
complete disappearance of starting material, which required 10 min
(Table II). Carbon tetrachloride (2 10 ml) was added to the reaction
mixture and after vigorous stirring the mixture was filtered and the
solvent was evaporated. The methyl phenyl sulfoxide was obtained in
98% yield as revealed from 1H-NMR analysis, m.p. 30–32 C [Lit.15 m.p.
32–33 C].
Oxidative Coupling of Thiols 4 to Disulfides 5 with
Reagent 1 under Solvent-Free Conditions
Typical Procedure
Thiophenol (1 mmol, 0.11 g) and reagent 1 (1 mmol, 0.47 g) were
mixed thoroughly using a pestle and mortar. The reaction mixture was
placed in air at room temperature with further mixing for 5 min. On
completion of the reaction, monitored by TLC, the product was extracted
into carbon tetrachloride (2 10 ml). The removal of solvent under re-
duced pressure afforded pure diphenyl disulfide in 99% yield, m.p. 59–
61 C [Lit.16e m.p. 58–61 C].

Solid State Oxidation
2283
Competitive Reaction
Typical Procedure
A mixture of benzyl alcohol (1 mmol, 0.11 g), thioanisole (1 mmol,
0.12 g) and oxidizing reagent 1 (1.5 mmol, 0.7 g) in a mortar by pestle
was ground, until TLC showed complete disappearance of benzyl al-
cohol (10 min). The crude reaction mixture was extracted into carbon
tetrachloride (2 15 ml) and the solvent was evaporated. The benzalde-
hyde and methyl phenyl sulfoxide were obtained in 98% and 0% yields
respectively as revealed from 1H-NMR analysis. The other competitive
reactions for Eqs. 1 and 3 are the same as above.
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