A recyclable fluorous thiourea organocatalyst for the chemoselective oxidation of sulfides

Article abstract of DOI:10.1016/j.jfluchem.2011.05.026

As a kind of organocatalyst, 1-[4-(perfluorooctyl)phenyl]-3-phenylthiourea was employed to the chemoselective oxidation of sulfides in the presence of 30% H₂O₂. A variety of diaryl, dialkyl, alkyl aryl sulfides could be oxidized to s

Full text of DOI:10.1016/j.jfluchem.2011.05.026

Journal of Fluorine Chemistry 132 (2011) 554–557
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Journal of Fluorine Chemistry
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Short communication
A recyclable fluorous thiourea organocatalyst for the chemoselective
oxidation of sulfides
Yi-Bo Huang a,b, Wen-Bin Yi a, Chun Cai a,
*
a School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing 210094, China
b Department of Pharmacy, Changzhou Institute of Engineering Technology, Changzhou 213164, China
A R T I C L E I N F O
A B S T R A C T
Article history:
As a kind of organocatalyst, 1-[4-(perfluorooctyl)phenyl]-3-phenylthiourea was employed to the
chemoselective oxidation of sulfides in the presence of 30% H2O2. A variety of diaryl, dialkyl, alkyl aryl
sulfides could be oxidized to sulfoxide under the mild condition. The catalyst could be easily recovered
by fluorous solid-phase extraction for reuse.
Received 28 March 2011
Received in revised form 24 May 2011
Accepted 26 May 2011
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
Fluorous thiourea
Organocatalyst
Oxidation
Fluorous solid-phase extraction (F-SPE)
1. Introduction
bearing long fluorous chain C8F17– had better retention behavior
than catalyst 1 in the fluorous gel, which was favorable for the
Compared with the traditional metal-based catalyst, organo-
catalyst has drawn much attention, owing to its low toxicity,
operational simplicity and high efficiency [1]. However, some
drawbacks also gradually appear with the application of organo-
catalyst. The major disadvantages are the high loading (up to
20 mol%) and the difficulty of recovering the catalyst. As a result,
some alternative strategies, i.e. immobilization technique [2,3] and
fluorous tag technique [4] have been developed to recycle the
organocatalysts.
Recently Curran’s group have elaborated a recycling tech-
nique by the fluorous solid-phase extraction (F-SPE) methodol-
ogy using fluorous silica gel [5]. Then some fluorous
orgnocatalysts have been designed for a variety of reactions,
and could be recovered by F-SPE. In our previous work, 1-[4-
(perfluorooctyl)phenyl]-3-phenylthiourea 2 (Scheme 1) have
been prepared and applied to the reductive amination [6].
Moreover, the fluorous thiourea catalyst could perform in the
reactions as well as the Schreiner catalyst of N, N0-bis[3,5-
bis(trifluoromethyl)phenyl]thiourea 1 (Scheme 1) [7]. The most
important one is that the catalyst 2 could be recovered much
easier than the catalyst 1 by F-SPE. It was because that catalyst 2
recovering the catalyst during F-SPE.
Organosulfur compounds, such as sulfoxides and sulfones, are
useful synthetic agents in organic chemistry. In particular,
sulfoxides are valuable synthetic intermediates for the produc-
tion of therapeutic agents [8]. Generally, sulfoxides could be
obtained by the oxidation of sulfides. Many oxidizing reagents
could be used to accomplish this transformation [9]. Among them,
hydrogen peroxide is the most attractive one because of its low
cost and cleanness. In the previous reports, H2O2/acetone [10],
H2O2/methanol [11], and H2O2/acetic acid [12] were employed to
oxidize dialkyl sulfides and some aryl sulfides. In these methods,
several fold equivalents of hydrogen peroxide were needed and
longer time was demanded. In addition, these methods were
unsuitable for the oxidation of diaryl sulfide [10,11] and some
sensitive substrates [12]. Later, all kinds of the improved
oxidation methods, especially by the use of transition metal (V,
Mo, Ti) ion [9], were developed so as to overcome these
drawbacks. But organocatalytic oxidative system was seldom
reported [13,14].
As far as we know, all kinds of the substituted thiourea could
effectively catalyze the organic reactions due to the double
hydrogen bond activation [7]. In 2009, Lattanzi et al. [15] reported
the first example of sulfoxidation with tert-butyl hydroperoxide
(TBHP) mediated by the thiourea 1. Inspired by their idea, we
applied the fluorous thiourea 2 to the oxidation of sulfides with
* Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.05.026

Y.-B. Huang et al. / Journal of Fluorine Chemistry 132 (2011) 554–557
555
CF3
CF3
C8F17
S
S
C
C
N
H
N
H
CF3
N
H
N
H
CF3
1
2
Scheme 1. Two kinds of thiourea catalyst.
30% hydrogen peroxide. To our delight, the catalyst exhibited good
catalytic activity and selectivity in the reaction.
recovered 2 retained its catalytic activity for five cycles (Table 2)
without further purification.
Next, oxidation of a variety of sulfides was examined in order to
demonstrate the scope of reaction as revealed in Table 3, all the
reactions could give the products in moderate to excellent yields.
Initially, different phenyl substituted sulfides were examined
under the optimized condition. The substrates bearing electron
withdrawing group such as para-nitro, exhibit higher activity than
the other ones, and the yield was 98% (Table 3, entry 4). However,
for para-methyl and para-chloro substituents, longer time was
required to obtain the products with high yields (Table 3, entries 2
and 3). As for entry 5, an equimolar amount of para-nitro (1 mmol)
and para-methyl sulfides (1 mmol) is treated with 1 mmol of 30%
H2O2 in the presence of the thiourea catalyst, the product could be
obtained with 4-nitrophenyl methyl sulfoxide (72%) and 4-
methylphenyl methyl sulfoxide (26%). It could be explained that
substituent bearing electron withdrawing group was more active
than it of electron donating group. In addition, we explored the
processes with some steric substrates of diphenyl sulfide and
thioxanthone. We found that the reaction rate slowed down
significantly, and the reaction yields were not high (Table 3, entries
6 and 7). The results showed that the steric effects seemed to play
an important role in the sulfoxidation.
In order to investigate the reactivity of the substrates with
dialkyl group, diethyl sulfide was examined further. We found that
the corresponding product was obtained in 97% yield (Table 3,
entry 8). While one alkyl group was replaced with benzyl, the
reaction was also proceeded efficiently in high yield (Table 3, entry
9). Furthermore, sulfides with functional group such as C55C were
also found to be well tolerated during the oxidative process. A
variety of sulfides were smoothly transformed into sulfoxides in
our oxidative system. Meanwhile, the sulfones were not deter-
mined by GC–MS in the products.
2. Results and discussion
In our experiment, catalyst 2 could be easily prepared by phenyl
isothiocyanate and perfluorooctyl aniline in THF [6]. At the
beginning, we carried out
sulfoxidation of methyl phenyl sulfide with 30% hydrogen
peroxide.
a model reaction involving the
As seen from Table 1, the solvent had a pronounced effect on the
yield. In the absence of catalyst, the transformation of sulfides to
sulfoxides was difficult to proceed under the above conditions
(Table 1, entries 1–5). From these results, we found that the
sulfoxides obtained in the solvent of CH2Cl2 or CH3OH were higher
than those in the other solvents. When catalyst 1 or 2 was loaded to
the reaction, the oxidation of sulfides proceeded smoothly in
CH2Cl2 (Table 1, entries 7 and 9). Unfortunately, the corresponding
yields were not high with CH3OH as a solvent (Table 1, entries 6
and 8), which could be explained by the inhibition of catalyst
activity due to intermolecule hydrogen bonding [15].
Next, the effect of catalyst loading on the results was also
evaluated. When catalyst loading was changed from 2 mol% to
5 mol%, the yields of sulfoxides were increased from 85% to 95%
(Table 1, entries 10–12). When 10 mol% of catalyst was used, the
yield did not increase significantly (Table 1, entry 9). In addition,
methyl phenyl sulfone as a kind of by-product of over oxidation
was not determined by GC–MS.
With the optimized reaction conditions in hand, we next
examined the recovery of catalyst 2. After the reaction was
finished, the mixture was concentrated and then loaded onto a
FluoroFlash1 silica gel cartridge for F-SPE. It was found that the
catalyst 2 could be cleanly recovered (92–95%). The corresponding
product purity was above 98.5% with HPLC analysis. Meanwhile,
the organocatalyst 2 could be repeatedly reusable. In each run, the
As shown in entries 2, 6 and 8, the corresponding catalyst could
be recycled more than three times with high reactivity. In addition,
all products listed in Table 3 are known compounds. In addition, all
products listed in Table 3 are known compounds and their
structures were determined by 1H NMR, 13C NMR and by GC–MS,
which were in accordance with the literatures.
Table 1
Oxidation of methyl phenyl sulfide to methyl phenyl sulfoxide with H2O2 catalyzed
by fluorous thiourea catalyst 1 or 2.a
Entry
Catalyst (mol%)
Solvent
Time (h)
Yield (%)b
1
2
None
None
None
None
None
1 (10)
1 (10)
2 (10)
2 (10)
2 (5)
CH3OH
CH3CN
CH2Cl2
THF
24
24
24
24
24
12
12
12
12
12
12
16
28
22
31
13
10
76
95
80
97
95
85
88
Table 2
Recycling and reuse of the fluorous organocatalyst 2 by F-SPE.a
3
4
Run
Recovered catalyst (%)b
Yield of product (%)c
5
Toluene
CH3OH
CH2Cl2
CH3OH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
6
Initial use
100
95
95
93
92
90
95
93
92
90
90
89
7
First reuse
Second reuse
Third reuse
Fourth reuse
Fifth reuse
8
9
10
11
12
2 (2)
2 (2)
a
Reaction condition: methyl phenyl sulfide 2 mmol, H2O2 4 mmol, CH2Cl2 2 mL,
a
Reaction condition: methyl phenyl sulfide 2 mmol, H2O2 4 mmol, solvent 2 mL,
catalyst 2.5 mol%, reaction time 12 h, room temperature 25 8C.
b
room temperature 25 8C.
Recovered by F-SPE.
b
c
Isolated yield after column chromatography.
Isolated yield after column chromatography.

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Y.-B. Huang et al. / Journal of Fluorine Chemistry 132 (2011) 554–557
Table 3
Chemoselective oxidation of sulfides with fluorous thiourea/H2O2 system.a
Entry
1
Sulfide 3
Sulfoxide 4
Time (h)
12
Yield 4 (%)b
95
2
3
16
16
16
82
80
79
16
10
16
90
4
5
98c
26d
72
6
7
24
24
24
78
78
76
32
76c
8
9
8
8
8
97e
95
92
8
95
10
24
83
11
8
92e
a
Reaction condition: sulfide 2 mmol, H2O2 4 mmol, catalyst 2.5 mol%, CH2Cl2 2 mL, room temperature 25 8C.
Isolated yield after column chromatography.
b
c
5 mL CH2Cl2 was required to ensure to dissolve substrates.
d
e
1 mmol 3b and 1 mmol 3d, H2O2 1 mmol, catalyst 2.5 mol%, CH2Cl2 2 mL, room temperature 25 8C.
Yields were determined by GC.

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557
3. Conclusions
Acknowledgments
In summary, a kind of fluorous organocatalyst was applied to
the chemoselective oxidation of sulfides in presence of 30% H2O2. A
variety of diaryl, dialkyl, alkyl aryl sulfides could be afforded to
sulfoxide under the mild condition. The fluorous organocatalyst
could be easily recovered by F-SPE for reuse.
We thank the project of ‘‘Excellent Initiative’’ and ‘‘Zijin Star’’ in
NJUST, ‘‘Doctoral Fund of Ministry of Education of China’’
(200802881024), and ‘‘National Natural Science Foundation of
China’’ (20902047) for financial support.
References
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