A recyclable TEMPO catalyst for the aerobic oxidation of sulfides to sulfoxides

Article abstract of DOI:10.1002/cssc.201000105

The aerobic oxidation of sulfides is accomplished by using a modified version of the TEMPO catalyst (A). The catalyst is active towards a wide range of substrates. In addition, it can be readily recovered by simple filtration and reused without loss of activity.

Full text of DOI:10.1002/cssc.201000105

DOI: 10.1002/cssc.201000105
A Recyclable TEMPO Catalyst for the Aerobic Oxidation of Sulfides to
Sulfoxides
[
a]
Tamilselvi Chinnusamy and Oliver Reiser*
Nowadays a wide range of reagents is available for almost
every conceivable type of oxidation, however, in many instan-
ces the use of these reagents still has disadvantages such as
high costs, difficulties in handling, toxicity, or lack of stability.
Therefore, the development of catalytic systems that display a
high atom economy while using comparatively harmless oxi-
dants, such as dioxygen, hydrogen peroxide, or hypochlorite, is
desired.
[
a]
Table 1. Aerobic oxidation of sulfides with TEMPO (Scheme 1).
1
2
[b]
Entry
R
R
Time [h]
Yield [%]
[c]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Me
Me
1.5
4
4
6
5
58
94
96
91
89
92
93
79
81
68
0
C
2
H
5
iPr
2-Naphthyl
Me
Me
Me
Me
Ph
4-Me-C
4-OMe-C
4-Cl-C
PhCH
Ph
6
H
4
3
3
The selective oxidation of sulfides into the corresponding
sulfoxides is one of the most important transformations in or-
ganic synthesis because of its usefulness for the preparation of
6
H
4
6
H
4
15
12
24
24
7
[
d]
[
9
1
2
d]
0
Ph
Me
[1,2]
biologically and medicinally valuable intermediates.
The
1
1
4-CHO-C
6
H
4
chemoselective oxidation of sulfides to sulfoxides can be ach-
ieved directly with molecular dioxygen, requiring high pressure
12
C
C
3
2
H
H
7
C
C
3
2
H
H
7
98
92
86
13
5
5
6
[
3,4]
14
iPr
iPr
6
and elevated temperature conditions.
Consequently, a
[
a] Sulfide (1.0 mmol) in AcOH (2 mL), Mn(NO
(NO O (2.0 mol%), TEMPO (1.0 mol%), oxygen atmosphere, 408C.
b] Isolated yield. [c] Determined by HNMR. [d] 5 mol% each of TEMPO,
Mn(NO O, and Co(NO
3 2
)2·4H O (2.0 mol%), Co-
number of alternative methods have been developed for this
[
5–7]
3 2
)2·6H
transformation,
among them a few catalytic systems that
1
[
[8]
allow the use of atmospheric oxygen as secondary oxidant.
3
)
2·4H
2
3 2
)2·6H O
Relevant to this work, the catalytic oxidation of sulfides to sulf-
oxides by oxoammonium ions generated from TEMPO by a
one-electron transfer mechanism was achieved either with
[
9]
sodium hypochlorite or with hydrogen peroxides in the pres-
obtained in 94% yield, with no observable oxidation to the
corresponding sulfone. Control experiments revealed that all
components of the catalyst mixture as well as molecular
oxygen are necessary for complete turnover of the substrate,
although the oxidation also proceeded to an appreciable
extent (30%) in the absence of TEMPO. Moreover, as reported
[
10]
ence of Cu-salen catalysts.
In the course of our ongoing studies to develop environ-
mentally benign catalytic processes for the oxidation of alco-
[
11]
hols, we found that Minisci’s conditions, that is, the aerobic
oxidation of alcohols with TEMPO in the presence of catalytic
[
12]
[12]
amounts of manganese and cobalt nitrate, can be extended
to the oxidation of sulfides. We report here the results of this
study by applying unmodified TEMPO and, more importantly, a
supported TEMPO catalyst of equal activity that can be readily
recovered by simple filtration, and reused.
for the analogous oxidation of alcohols, acetic acid proved
to be the solvent of choice: no oxidation took place either in
dichloromethane or acetonitrile.
Under the optimized conditions, a representative range of
sulfides was evaluated. We were pleased to find that diaryl-
and dialkyl- as well as arylalkylsulfides were smoothly convert-
ed into the corresponding sulfoxides in high yields. This was
also true for electron-rich sulfides; further oxidation to sulfones
was not observed. It was necessary to prolong reaction times
and/or catalyst loading for some, especially electron-deficient,
sulfides (Table 1, entries 8–10), to the point that oxidation did
not proceed at all (Table 1, entry 11).
Choosing thioanisole as the model substrate, we investigat-
ed a catalyst mixture comprising TEMPO (1 mol%), Mn-
(
NO ) 4H O (2 mol%), and Co(NO ) 6H O (2 mol%) in acetic
3 2· 2 3 2· 2
acid at 408C (Scheme 1). After a reaction time of 4 h under am-
bient pressure of dioxygen (Table 1, entry 2) the sulfoxide was
Because both alcohols and sulfides can be oxidized under
the reaction conditions described here, we subsequently inves-
tigated the chemoselectivity (Scheme 2). We found a high pref-
erence for alcohol oxidation when both functional groups
were present in a substrate. For example, oxidation of 1 gave
rise to 2 in quantitative yield, demonstrating that alcohol oxi-
dation is much more facile than sulfide oxidation under the ap-
plied reaction conditions. Nevertheless, oxidation of the sul-
fides occurred smoothly after protecting 1 as methyl ether 3,
suggesting that the hydroxymethyl group in 1 has not simply
deactivated the methyl sulfide by virtue of its electron-with-
Scheme 1. Aerobic oxidation of sulfides.
[a] T. Chinnusamy, Prof. O. Reiser
Institut fꢀr Organische Chemie
Universitꢁt Regensburg
Universitꢁtsstr. 31, 93053 Regensburg (Germany)
Fax: (+49)9419434121
E-mail: oliver.reiser@chemie.uni-regensburg.de
1
040
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2010, 3, 1040 – 1042

[
a]
Table 2. Aerobic oxidation of phenyl methyl sulfide.
[
b]
Entry
Catalyst
Sulfoxide [%]
1
2
3
4
TEMPO
58
57
38
57
5
6
7
[
(
1
a] Sulfide (1.0 mmol) in AcOH (2 mL), Mn(NO
NO O (2.0 mol%), catalyst (1.0 mol%), oxygen atmosphere, 408C,
.5 h. [b] Determined by H NMR.
3 2
)2·4H O (2.0 mol%), Co-
3 2
)2·6H
1
[11c]
vations for the oxidation of alcohols.
Moreover, with other
sulfides 7 showed the same activity as that found with TEMPO
(
Table 3, cf. Table 1).
Recovery of 7 can be achieved by simple filtration of the re-
action mixture through a standard sintered glass funnel (P40,
6–40 mm pore size), and it can then be reused without further
1
purification. For example, in this manner the oxidation of thio-
anisole to its sulfoxide was carried out in five cycles, in 92–
Scheme 2. Chemoselectivity between alcohols and methyl sulfides in aerobic
TEMPO oxidations.
98% yield (Table 4) with an initial catalyst amount of 1 mol%
of 7, of which a total of 70% could still be recovered after the
fifth run (i.e., >90% for each cycle). We attribute the overall
loss of catalyst to transfer operations of the catalyst between
the filter and the reaction flask. HPLC-MS analysis of the recov-
drawing nature. Moreover, oxidation of a mixture of benzyl al-
cohol and phenyl methyl sulfide favored the oxidation of the
alcohol, with a selectivity of at least 8:1.
Despite the high efficiency of TEMPO for the sulfide oxida-
tion, its high cost calls for recyclable versions of this catalyst.
Recently, our group reported TEMPO derivatives 5–7 (Figure 1)
[a]
Table 3. Aerobic oxidation of sulfides using catalyst 7 (Scheme 1).
1
2
[b]
Entry
R
R
Time [h]
Yield [%]
1
2
3
4
5
6
7
Ph
Ph
Ph
Me
4
4
6
5
3
90
92
92
91
93
89
82
61
82
91
95
90
C
2
H
5
iPr
2-Naphthyl
4-Me-C
4-OMe-C
4-Cl-C
Ph
Me
Me
Me
Me
Ph
6
H
4
6
H
4
3
6
H
4
15
24
12
7
6
6
[
c]
c]
8
9
1
[
PhCH
2
Ph
0
C
C
3
2
H
H
7
C
C
3
2
H
H
7
1
1
5
5
12
iPr
iPr
[
(
a] Sulfide (1.0 mmol) in AcOH (2 mL), Mn(NO
NO O (2.0 mol%), 7 (1.0 mol%), oxygen atmosphere, 408C. [b] Iso-
O, and Co-
3 2
)2·4H O (2.0 mol%), Co-
3 2
)2·6H
lated yield. [c] 5 mol% each of TEMPO, Mn(NO
NO
3 2
)2·4H
(
3 2
)2·6H O
Figure 1. Supported TEMPO derivatives.
[
a]
Table 4. Recycling of catalyst 7 in the oxidation of thioanisole.
that allowed recovery either by chromatography (5) or by
simple filtration (6 and 7); the latter due to its heterogeneous
[
b]
[c]
Entry
Run
Conversion
%]
Yield
[%]
Recovery of
catalyst [mg]
[
[
11a–c]
nature.
Applying 5, soluble in acetic acid, for the oxidation
1
2
3
4
5
1
2
3
4
5
>98
>98
>98
>98
>98
98
98
90
92
95
56
54
51
45
40
of phenylmethyl sulfide under limiting conditions that allow an
assessment of catalyst activity not unexpectedly revealed the
same activity as TEMPO itself (Table 2, entries 1 and 2). Howev-
er, catalysts 6 and 7, being heterogeneously dispersed in
acetic acid, showed remarkable differences in activity: while
the activity of 6 substantially dropped, 7 retained the activity
of homogeneous TEMPO, consistent with our previous obser-
[a] Sulfide (3.0 mmol) in AcOH (6 mL), Mn(NO
NO
2 h. [b] Determined by H NMR. [c] Isolated yield.
3
)
2·4H
2
O (2.0 mol%), Co-
(
1
3 2
)2·6H O (2.0 mol%), 7 (60 mg, 1.0 mol%), oxygen atmosphere, 408C,
1
ChemSusChem 2010, 3, 1040 – 1042
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
1041

ered catalyst 7 did not give any indication for degradation or,
especially, cleavage of the TEMPO moiety from its central unit:
the only additional compounds besides 7 that were present in
small amounts were the corresponding oxoammonium cation
acting as the active oxidant in the process and the correspond-
ing piperidine derivative resulting from deoxygenation of
TEMPO 7. No formation of N-nitrosamines, which can be envi-
Acknowledgements
This work was supported by the Deutsche Forschungsgemein-
schaft (SPP 1179 Organokatalyse) and the Evonik foundation (fel-
lowship for T.C.).
Keywords: chemoselectivity · organocatalysis · oxidation ·
perfluorinated catalysts · sulfur
[14]
sioned from reaction of TEMPO and nitrates, was detected.
It is tempting to speculate that the fluorous chains in 7 in-
crease the local oxygen concentration, as known for flourous
[
13]
[1] P. Metzner, A. Thuillier; Sulfur Reagents in Organic Synthesis, Academic
Press, London, 1994.
media, to account for the superior activity in comparison to
, however, we have no direct experimental evidence to sup-
6
[
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Rappoport, C. J. M. Stirling), Wiley, Chichester, 1994.
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In conclusion, we have developed a highly efficient protocol
for the aerobic oxidation of sulfides to sulfoxides using catalyt-
ic amounts of TEMPO in combination with manganese and
cobalt nitrate. Moreover, with heterogeneous 7 a readily recov-
erable and reusable catalyst is identified, displaying the same
activity as unmodified TEMPO.
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Aerobic oxidation of sulfides to sulfoxides by TEMPO: Sulfide
(
1.0 mmol),
Mn(NO ) 4H O
(0.02 mmol),
Co(NO ) 6H O
3 2· 2
3
2·
2
(
0.02 mmol), TEMPO (0.01 mmol), and glacial acetic acid (2 mL)
were added to a Schlenk flask and heated at 408C under an
oxygen atmosphere until completion. The reaction mixture was
[
[
8] C. Mꢂrcker, Justus Liebigs Ann. Chem. 1965, 136, 75.
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Skarzewski, Synlett 1996, 757.
washed with water and extracted with CH Cl . The organic layer
2
2
was washed with water (2ꢁ10 mL), dried over Na SO , and concen-
2
4
trated under vacuum to afford the corresponding sulfoxide.
[10] S. Velusamy, A. V. Kumar, R. Saini, T. Punniyamurthy, Tetrahedron Lett.
005, 46, 3819–3822.
2
Aerobic oxidation of sulfides to sulfoxides by 7: Sulfide (1.0 mmol),
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Mn(NO ) 4H O (0.02 mmol), Co(NO ) 6H O (0.02 mmol), catalyst 7
3
2·
2
3 2·
2
(
20 mg, 1 mol%), and glacial acetic acid (2 mL) were added to a
Schlenk flask and heated at 408C under an oxygen atmosphere
until completion. The reaction mixture was filtered, and then
washed with water and CH Cl . The organic layer was washed with
8
262–8266; e) S. Jain, O. Reiser, ChemSusChem 2008, 1, 534–541.
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2
2
[
[
water (2ꢁ10 mL), dried over Na SO , and concentrated under
2
4
4
vacuum to afford the corresponding sulfoxide.
Recycling experiment for the aerobic oxidation of thioanisole by
catalyst 7: Thioanisole (366 mg, 3 mmol), Mn(NO ) 4H O (15 mg,
3
2·
2
[
14] We thank one of the referees for raising this question, which would
have resulted in the formation of carcinogenic N-nitrosamine byprod-
ucts. Within our detection limits (HPLC-MS) we did not observe such
impurities. Moreover, those would still be bound to the support, thus
pointing to an additional advantage in using immobilized TEMPO cata-
lysts. Further investigations to address this important aspect are being
carried out in our laboratories.
0
1
.06 mmol), Co(NO ) 6H O (18 mg, 0.06 mmol), TEMPO 7 (60 mg,
3 2· 2
mol%), and glacial acetic acid (6 mL) were added to a Schlenk
flask and heated at 408C under an oxygen atmosphere. After 12 h
the reaction mixture was filtered, and washed with water and
CH Cl . The organic layer was washed with water (2ꢁ10 mL), dried
2
2
over Na SO and concentrated under vacuum to afford the sulfox-
2
4
ide. Catalyst 7 was washed with water and CH Cl and reused with-
2
2
out further purification. Fresh portions of Mn(NO ) 4H O (15 mg,
3
2·
2
Received: April 1, 2010
0
.06 mmol) and Co(NO ) 6H O (18 mg, 0.06 mmol) were added
Revised: May 9, 2010
3
2·
2
before each run.
Published online on July 15, 2010
1
042
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2010, 3, 1040 – 1042