4652
X.-T. Zhou et al. / Bioorg. Med. Chem. Lett. 17 (2007) 4650–4653
O
S
-4
Ru(TPP)Cl (2x10 mmol)
S
o
toluene(50 mL), isobutyraldehyde(0.1 mol), O (1atm), 4 h, 80 C
2
Isolated Yield: 92%
TON: 92, 000
20 mmol
Scheme 2. Large-scale oxidation of thioanisole catalyzed by Ru(TPP)Cl.
Temperature is another important factor to influence the
selectivity of thioanisole oxidation to sulfoxide catalyzed
by Ru(TPP)Cl in presence of molecular oxygen. Only
75% thioanisole could be oxidized by conducting the
reaction under 70 ꢁC for 90 min (entry 11), and when
the temperature rose to 90 ꢁC, the poorer selectivity of
sulfoxide could be obtained accordingly (entry 12).
When the amount of Ru(TPP)Cl catalyst was
2 · 10À4 mmol, sulfoxide could be obtained with the iso-
lated yield of 92% by conducting the reaction for 4 h. It
should be mentioned that the turnover number of the
present catalyst could exceed 90 thousands. To our best
knowledge, the oxidation reaction system for sulfide to
sulfoxide catalyzed by metalloporphyrins in the presence
of molecular oxygen has never been reported before
with such high TON value.
Encouraged by the excellent catalytic performance for
the thioanisole oxidation to sulfoxide, different sulfides
were subjected to the reaction system in the presence of
molecular oxygen, and the results are listed in Table 2.
Conclusions. Sulfoxidation of sulfides by molecular oxy-
gen was efficiently enhanced by using Ru(TPP)Cl as cat-
alyst and isobutyraldehyde as oxygen acceptor. Under
80 ꢁC and atmospheric pressure, the catalytic system
presented high activity and selectivity for the oxidation
of sulfides to sulfoxides. In a large-scale experiment of
thioanisole oxidation, the isolated yield of sulfoxide
was 92%. The turnover number of the present catalyst
could exceed 90 thousands.
As in Table 2, all substrates could be smoothly con-
verted to sulfoxides with high conversion rates, and
excellent selectivities were obtained by Ru(TPP)Cl cata-
lyst and molecular oxygen as the sole oxidant. More-
over, it can be observed that the electronic property of
substrate affects the reaction rate (entries 1–4). It
required a slightly longer reaction time for substrate
with electron-withdrawing groups (entry 4). The influ-
ence of steric effects could further be found from the oxi-
dation of diphenyl sulfide and isopropyl phenyl sulfide.
The conversion rates of diphenyl sulfide and isopropyl
phenyl sulfide were 98%, 93% after much longer reac-
tions time (entries 5 and 6). Comparing with thianisole,
methyl benzyl sulfide presents the similar reaction
behavior, and it could be stoichiometrically converted
under the same conditions (entry 7). Sulfoxidation of
the linear chain di-n-butyl sulfide smoothly proceeded
in less reaction time with high conversion and yields (en-
try 8). Cyclic sulfide, that is, 1,4-thioxane, could also be
efficiently sulfoxidated to the corresponding sulfoxide
with 94% conversion and 97% selectivity (entry 9).
Acknowledgments
The authors thank the National Natural Science Foun-
dation of China (20576045) and the Program for New
Century Excellent Talents in University (NCET) for
providing financial support for this project.
References and notes
1. (a) Patai, S.; Rappoport, Z. Synthesis of Sulfones, Sulfox-
ides, and Cyclic Sulfides; John Wiley: Chichester, 1994; (b)
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Carreno, M. C. Chem. Rev. 1995, 95, 1717; (d) Holland,
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W. H.; Dyszlewski, A. D. J. Org. Chem. 1990, 55, 955; (f)
Madesclaire, M. Tetrahedron 1986, 42, 5459.
2. Meunier, B. Biomimetic Oxidations Mediated by Metal
Complexes; Imperial College Press: London, 2000.
3. Oae, S.; Watanabe, Y.; Fujimori, K. Tetrahedron Lett.
1982, 23, 1192.
4. Zhou, Q. L.; Chen, K. C.; Zhu, Z. H. J. Mol. Catal. 1991,
64, 19.
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Soc. 1989, 111, 3958; (b) Huang, J. Y.; Li, S. J.; Wang, Y.
G. Tetrahedron Lett. 2006, 47, 5637.
Despite high efficiency, another salient feature of the
present sulfoxidation system is its high chemo-selectiv-
ity. For oxidation of hydroxyl group-containing sulfide,
for example, 2-(phenylthio) ethanol (entry 10), sulfide
can be entirely converted and the yields of sulfoxide
could reach 90%, and 10% yield of the corresponding
aldehyde was found in products. It demonstrates that
the sulfide functional group is highly reactive, but
hydroxyl group could hardly be activated under such
reaction conditions.
6. Campestrini, S.; Tonellato, U. J. Mol. Catal. A 2000, 164,
263.
It should be mentioned that the present reaction system
was highly selective. Sulfoxides could be nearly stoichio-
metrically produced, and the generation of the corre-
sponding sulfones was well controlled, which makes
this process a good alternative for sulfoxide production.
7. (a) Marques, A.; Marin, M.; Ruasse, M. F. J. Org. Chem.
2001, 66, 7588; (b) Penenory, A. B.; Arguello, J. E.;
Puiatti, M. Eur. J. Org. Chem. 2005, 114; (c) Baciocchi, E.;
Gerini, M. F.; Lapi, A. J. Org. Chem. 2004, 69, 3586; (d)
Baciocchi, E.; Gerini, M. F.; Lanzalunga, O.; Lapi, A.
Org. Biomol. Chem. 2003, 1, 422; (e) Doerge, D. R.;
Cooray, N. M.; Brewster, M. E. Biochemistry 1991, 30,
8960.
Large-scale thioanisole oxidation experiment was car-
ried out as shown in Scheme 2.15