An efficient and selective aerobic oxidation of sulfides to sulfoxides catalyzed by Fe(NO3)3-FeBr3

Article abstract of DOI:10.1016/S0040-4039(01)01490-3

The binary system Fe(NO₃)₃-FeBr₃ is a very efficient catalyst for the selective air-oxidation of sulfides to sulfoxides. Since the oxidation is selective, it may be applied to any type of dialkyl and alkyl aryl sulfide, as

Full text of DOI:10.1016/S0040-4039(01)01490-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7147–7151
An efficient and selective aerobic oxidation of sulfides to
sulfoxides catalyzed by Fe(NO3)3–FeBr3
Sandra E. Mart´ın* and Laura I. Rossi
INFIQC, Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas, Universidad Nacional de Co´rdoba,
Ciudad Universitaria, 5000 Co´rdoba, Argentina
Received 10 April 2001; revised 11 August 2001; accepted 13 August 2001
Abstract—The binary system Fe(NO3)3–FeBr3 is a very efficient catalyst for the selective air-oxidation of sulfides to sulfoxides.
Since the oxidation is selective, it may be applied to any type of dialkyl and alkyl aryl sulfide, as well as to substrates of biological
interest. It develops in mild conditions, giving a high yield in the presence of different functional groups on the sulfide. Other
binary systems such as Fe(NO3)3–FeBr2 and Cu(NO3)2–CuBr2 are also effective catalysts for sulfoxidation. In contrast to previous
oxygenation methods, this oxidation requires neither an aldehyde nor a transition metal complex. © 2001 Elsevier Science Ltd.
All rights reserved.
The oxidation of sulfides to sulfoxides has been the aim
of considerable research due to the importance of sul-
foxides as useful intermediates in organic synthesis and
the key roles some of them play in the activation of
enzymes.1 Many oxidants are available to perform this
key transformation.2 Unfortunately one or more equiv-
alents, often hazardous or toxic oxidizing agents, are
usually required. Otherwise overoxidation of sulfides
resulting in sulfone formation and undesired reactions
of other functional groups are common problems, par-
ticularly when preparing biologically relevant sulfox-
ides. From an economical and environmental
standpoint, catalytic oxidation processes are thus
extremely valuable, and those involving dioxygen are
particularly attractive. Dioxygen is an inexpensive, non-
toxic and easily available oxidant about which many
studies have been made for its eventual use in oxidation
reactions.3 At high dioxygen pressure and elevated tem-
peratures, a selective oxidation of sulfides to sulfoxides
can be achieved with high selectivity in the absence of
any catalyst.4 In addition, the high pressure oxygena-
tion is catalyzed by Ce(IV)5 or Ru(II)6 complexes.
Thus, most of the reported methods for the oxidation
of sulfides to sulfoxides using dioxygen require rather
high reaction temperatures, high pressure of dioxygen,
or long reaction times.7 Relatively few catalytic systems
using less pressure or atmospheric dioxygen have been
reported for this oxygenation.8 Recently, new methods
including dioxygen oxidation catalyzed by either a pal-
ladium complex,9 or a complex of Ru(III),10 and dioxy-
gen and aldehydes,11 have been developed. Although
the direct use of air under mild conditions is more
desirable, not many examples have been reported,
instead most of them are based on homogeneous cata-
lysts.12 Thus, catalytic systems that use dioxygen from
the air as secondary oxidant are greatly sought after.
On the other hand, clay-supported metallic nitrates
have been widely used as reagents in organic synthesis,
particularly in the field of oxidation and nitration.13
The reactivity of Fe(III) and Cu (II) montmorillonite-
supported metal nitrates (Clayfen and Claycop)
towards organic substrates has been extensively stud-
ied.14 Clayfen is unstable, but may be stored for a few
days under pentane and the preparation of the com-
pound also needs some caution.13a,b Several methods
for the oxidation of sulfides with metal nitrates have
been reported.12a,15 Such systems include hydrated
Fe(III) and Cu(II) nitrates under solvent free condi-
tions,16 and microwave thermolysis with Clayfen.17 In
all cases the metal nitrates are used as reagent. Iron is
an abundant, cheap and non-toxic metal. In a previous
work, we reported the selective oxidation of sulfides
with nitric acid catalyzed by FeBr3 and
[(FeBr3)2(DMSO)3].18 Mechanistic studies by electro-
chemical methods demonstrated that the high selectivity
exhibited was controlled by the transition metal, that
the role of nitric acid was to oxidize bromides into
bromine, and that this couple was the redox mediator
in sulfide oxidation.19
* Corresponding author. Tel.: 54-351-4334173; fax: 54-351-4333030;
e-mail: martins@dqo.fcq.unc.edu.ar
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01490-3

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S. E. Mart´ın, L. I. Rossi / Tetrahedron Letters 42 (2001) 7147–7151
1, Table 1). The binary catalyst was found to be very
selective, no further oxidation to sulfones was
evidenced.
Taking these results into account, and considering that
the use of an easy handling medium is much more
desirable than nitric acid, we decided to examine the
ability of Fe(NO3)3·9H2O in the presence of FeBr3 to
accomplish this oxidation. We have reported here some
of our recent results on a binary catalyst, Fe(NO3)3–
FeBr3, a selective and efficient catalytic system for the
oxidation of sulfides with air under mild conditions. To
the best of our knowledge, this is the first time that the
Fe(NO3)3·9H2O was used in a catalytic amount to carry
out oxidation. The advantage of this method is that it
does no demand a metal complex or any cooxidant,
such as an aldehyde.11
In order to improve the efficiency of this catalytic
system we investigated different ratios between the
metallic salt and the metal bromide. The best results
were found when the relation between the salts
Fe(NO3)3:FeBr3 was 1:0.5. When a molar ratio sub-
strate:Fe(NO3)3:FeBr3 1:0.05:0.025 was used as catalyst,
the reaction was completed in 4.5 hours (entry 2, Table
1). The use of a lesser amount of catalyst took a longer
time to react. No improved rates could be observed at
higher temperatures. When Fe(NO3)3 was used as cata-
lyst alone, the conversion of substrate was only about
26% (entry 3, Table 1), as expected according to previ-
ous data reporting this nitrate as an oxidation
regent.12a,15–17 However, the presence of FeBr3
enhanced the rate of oxidation, and turned the system
into a catalytic one, provided that the reaction was
The catalytic oxidation reaction of sulfides takes place
at room temperature, in CH3CN, under air in the
presence of Fe(NO3)3·9H2O (0.1 mmol%) and FeBr3
(0.05 mmol%) as catalysts (Eq. (1)).
O
−
carried out with a substrate:NO3 1:0.3 molar ratio.
Fe(NO3)3-FeBr3
Attempted oxidation with only FeBr3 under the same
conditions resulted in no reaction, and 1 remained
unchanged (entry 4, Table 1). Under a dioxygen atmo-
sphere the reaction proceeded in the same way as in air
(entry 5, Table 1). Otherwise, under a nitrogen atmo-
sphere, only 25% of the sulfide 1 was oxidized to 2 and
the remaining 1 was recovered (entry 6, Table 1).
Controls showed that under nitrogen atmosphere the
oxidation with Fe(NO3)3 took place in the same way as
in air (26%). Therefore, the catalytic oxidation reac-
tions with the binary catalyst Fe(NO3)3–FeBr3 system,
apparently need dioxygen for oxidation to take place. It
is interesting to note that the reaction does not require
a high pressure of dioxygen, in fact, it can be run at
room pressure with air. This is an important issue and
a great advantage from a safe handling viewpoint. The
aerobic oxidation can also be successfully carried out
S
S
(1)
Ph
Me
Ph
Me
CH3CN, 25°C
air
1
2
Other reaction solvents such as AcOEt or methylene
chloride rendered lower yields, and methanol or ben-
zene were not useful for this reaction. For our early
experiments we selected methyl phenyl sulfide (1) as the
model substrate, and the results are presented in Table
1. A typical experiment was run with a 1 mmol of the
substrate, but the reaction could be scaled up to 20
mmol without any change in the reaction products. An
excellent result for the oxidation reaction was obtained
using 1 at room temperature, which afforded the
methyl phenyl sulfoxide (2) with total selectivity in 98%
conversion and 92% isolated yield within 1 hour (entry
Table 1. Catalytic air oxidation of methyl phenyl sulfide (1) to methyl phenyl sulfoxide (2) at room temperaturea
Entry
Catalyst (% mmol)
Time (h)
Conditions
Yield of 2b (%)
1
2
3
4
5
6
7
8
Fe(NO3)3c–FeBr3
Fe(NO3)3–FeBr3
Fe(NO3)3
FeBr3
Fe(NO3)3–FeBr3
Fe(NO3)3–FeBr3
Fe(NO3)3–[(FeBr3)2(DMSO)3]
Fe(NO3)3–KBr
Fe(NO3)3–FeCl3
Fe(NO3)3–FeBr2
Zn(NO3)2g–ZnBr2
Cu(NO3)2h–CuBr2
1
Air
Air
Air
Air
98
99
26
d
4.50
1.50
1.50
1
1
5
1.50
1.50
4
3
3
N.R.e
98
f
O2
N2
f
25
96
20
21
Air
Air
Air
Air
Air
Air
9
10
11
12
89
N.R.e
82
a Reaction carried out with 1 mmol in an open system at room temperature, with molar ratio substrate:Fe(NO3)3:FeBr3 1:0.1:0.05 mmol, in 5 mL
of CH3CN.
b Determined by GC.
c Fe(NO3)3 corresponds to Fe(NO3)3·9H2O.
d Reaction carried out with a molar ratio substrate:Fe(NO3)3:FeBr3 1:0.05:0.025.
e N.R: Reaction did not occur.
f Under an O2 or N2 atmosphere (1 atm).
g Zn(NO3)2 corresponds to Zn(NO3)2·6H2O.
h Cu(NO3)2 corresponds to Cu(NO3)2·2.5H2O

S. E. Mart´ın, L. I. Rossi / Tetrahedron Letters 42 (2001) 7147–7151
7149
confirmed the catalytic role of the bromide together with
the Fe(III). This is also in agreement with the result found
in the oxidation of sulfides with nitric acid in a biphasic
with the complex [(FeBr3)2(DMSO)3] (entry 7, Table 1).
This complex was synthesized as previously reported.18b
The main advantage of the use of this coordination
compound is its high stability unlike anhydrous FeBr3,
which facilitates storage and handling. The only reports
ontheapplicationsofcoordinationcompoundsofDMSO
to iron or other transition metal halides in organic
reactions are the bromination of diphenyl sulfide;20 the
sulfide oxidations catalyzed with RuX2(DMSO)4, X=Cl,
Br;21 and the oxidation of sulfides by nitric acid catalyzed
by [(FeBr3)2(DMSO)3].18,19 The fact that the aerobic
oxidation of 1 took longer to be completed than those
performed with FeBr3 (entry 7, Table 1), could be
explained if the organic sulfide should coordinate to the
metal prior to oxidation and displace a DMSO ligand
before coordination, as previously reported.6,18,21 The
catalytic reaction proceeded hardly varying from FeBr3
to KBr (entry 8, Table 1). The observed sulfoxide may
be due to the oxidation reaction with Fe(NO3)3 as a
reagent. Evidently, the importance of the metal center
shows that the oxidation of the substrate is related to the
Fe(III) center of the halide salt, and that the catalytic
oxidation fails when this metal is absent. This is further
supported by the results of the reaction carried out with
Fe(NO3)3–[(FeBr3)2(DMSO)3], as previously discussed,
the presence of a ligand delayed oxidation, which means
that the metal center was less available for the coordina-
tion of the substrate. From all these findings, we may infer
that in a special manner Fe(III) controls oxidation.
19
system catalyzed by FeBr3 and FeCl3 or by tetra-
bromoaurate(III) and tetrachloroaurate,22 whereas in the
oxidation involving chlorides lower yields were obtained.
Furthermore, FeBr2 can also accomplish oxidation effec-
tively (entry 10, Table 1), and may truly be regarded as
a good alternative for this catalytic system. The catalytic
activity of various transition metal nitrates and bromides
was also examined. With the Zn(NO3)2·6H2O–ZnBr2
system, the oxidation of 1 did not occur (entry 11, Table
1). However, sulfoxide 2 was obtained more efficiently,
but still not as efficiently as in the iron catalytic system,
with Cu(NO3)2·2.5H2O–CuBr2 (entry 12, Table 1).
A series of sulfides was then reacted with this remarkably
simple procedure and the results are presented in Table
2. As shown, both aliphatic and aromatic sulfides were
oxygenated and most of the reactions proceeded nearly
quantitatively. All the reactions occurred with complete
selectivity for sulfoxide formation, no overoxidation
products such as sulfones were detected in the reaction
mixtures. The products could be readily isolated. The only
purification step consisted of a filtration through a silica
gel column leading to the products in excellent yields and
purities. A simple dialkyl sulfide, such as tert-butyl methyl
sulfide was efficiently oxidized (entry 1, Table 2). Besides,
aryl methyl sulfides were selectively converted to sulfox-
ides almost quantitatively (entries 2–6, Table 2). Interest-
ing results were obtained in the oxidation of the amino
On the other hand, keeping all other conditions constant,
the Fe(NO3)3–FeBr3 catalyst was replaced by Fe(NO3)3–
FeCl3. This system had very little catalytic activity, even
though it has Fe(III) (entry 9, Table 1). Although, there
was practically no reaction with KBr, the last result
acid N-(tert-butoxycarbonyl)-L-methionine. The pres-
ence of amide and carboxylic groups did not interfere with
the oxidation process of the sulfide (entry 7, Table 2).
Sulfoxide was obtained in good yields and in a 1:1 mixture
Table 2. Selective air oxidation of sulfides to sulfoxides using Fe(NO3)3–FeBr3 as catalysta

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S. E. Mart´ın, L. I. Rossi / Tetrahedron Letters 42 (2001) 7147–7151
Acknowledgements
of the two diastereoisomers with a different configuration
at the sulfur atom.23 The use of this catalytic system has
raised some questions about the nature of all active
species in the catalytic cycle. In a system like this, which
We are grateful to the Consejo Nacional de Investiga-
ciones Cient´ıficas y Te´cnicas (CONICET) and the Con-
sejo de Investigaciones Cient´ıficas y Tecnolo´gicas de la
Provincia de Co´rdoba (CONICOR), for financial
support.
−
contained NO3 and FeBr3, it is assumed that NO2 is
generated in situ, as proposed in a related system.12a
There are few examples of the direct use of NO2 as an
oxidation reagent in sulfoxidations.2a,8c Since the reac-
tion mixture became light brown, it is possible that it
might play a role in this oxidation, and thus the system
Fe(NO3)3–FeBr3 could be a source of NO2. However, we
also had to take into account the participation of other
species in our system. Mechanistic studies of the selective
oxidation of sulfides with nitric acid catalyzed by FeBr3
and [(FeBr3)2(DMSO)3], demonstrated that the selectiv-
ity of the reaction was due to the activation of sulfides
by coordination to the metal center, that the role of nitric
acid was to oxidize bromides into bromine, and that this
couple was the redox mediator in sulfide oxidation.19 In
our system the catalytic role of the bromides and the
control of the oxidation by Fe(III) was also demon-
strated. Furthermore, the oxidation potential of the
nitrates is too low for an efficient oxidation of chloride
into chlorine.19 This fact may account for the low yields
obtained from the oxidations by the Fe(NO3)3–FeCl3
system. Thus, in the catalytic cycle of our system an
oxidation where the active oxidant could be the bromide
and bromine couple as redox mediator and the sulfides
were activated by coordination to the metal, for oxygena-
tion, should be kept in mind.
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Fe(NO3)3–FeBr3 catalytic system was very effective for
the selective air-oxidation of several types of sulfides to
sulfoxides and it also succeeded with substrates of
biological interest. The reaction proceeded under very
mild conditions and in a simple procedure to the oxida-
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metal complex. Two types of active species may be
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General procedure. Oxidation reactions catalyzed by
Fe(NO3)3–FeBr3. A typical experiment was carried out in
an open reaction tube provided with a condenser. To the
mixture of Fe(NO3)3·9H2O (0.1 mmol) and FeBr3 (0.05
mmol) in 5 mL of CH3CN was added methyl phenyl
sulfide (1 mmol). The reaction mixture was stirred under
aerial conditions at room temperature. The reaction
progress was followed by GC and TLC. When the
reaction was complete, CH2Cl2 were added to the reac-
tion mixture and the two phases were separated. The
aqueous layer was extracted with CH2Cl2. The combined
organic layers were washed with water, dried over
MgSO4 and the solvent was removed in vacuo. The
residue was chromatographed on a silica gel (70–270
mesh ASTM) column, eluting with ethyl acetate/hexanes
using various ratios. All products were identified and
found to be identical to authentic samples.

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