Oxidation of amines and sulfides catalyzed by an assembled complex of phosphotungstate and non-cross-linked amphiphilic polymer

Article abstract of DOI:10.1055/s-2002-35596

Oxidation of sulfides and amines was performed with an assembled catalyst of phosphotungstate and non-cross-linked amphiphilic polymer. The reactions proceeded with hydrogen peroxide under organic solvent-free conditions. This insoluble catalyst was reused five times with the turnover number up to 500.

Full text of DOI:10.1055/s-2002-35596

LETTER
2031
Oxidation of Amines and Sulfides Catalyzed by an Assembled Complex of
Phosphotungstate and Non-Cross-Linked Amphiphilic Polymer
O
xidation of Amin
o
es and Sulfid
i
es chi M. A. Yamada, Hidetsugu Tabata, Hideyo Takahashi, Shiro Ikegami*
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
Fax +81(42)6853728; E-mail: shi-ike@pharm.teikyo-u.ac.jp
Received 24 September 2002
Abstract: Oxidation of sulfides and amines was performed with an
assembled catalyst of phosphotungstate and non-cross-linked am-
phiphilic polymer. The reactions proceeded with hydrogen peroxide
HN
O
under organic solvent-free conditions. This insoluble catalyst was
reused five times with the turnover number up to 500.
1
12
O
Key word: polymers, tungsten, oxidation, amines, sulfides
HN
Oxidation of sulfides and amines is one of the most impor-
tant and straightforward methods for the preparation of
sulfones, oximes and nitrones, which are utilized for the
biologically active substances and the substrates for the
synthesis of medicines.1 From the standpoint of green
chemistry, nowadays, environmental benign systems
for these oxidations are desirable. As a statement by the
IUPAC commission, a use of aqueous hydrogen peroxide
as an alternative to toxic oxidants, which is cheap and
clean oxidizer transformed into harmless water, is sustain-
able. Besides, a reliance of a reusable immobilized cata-
lyst without an organic solvent shows good promise in
incorporating these considerations.1c,2
N+Me2(C12H25
)
3-
PW12O40
3
n
1
Figure 1
the catalyst can be reused five times with the turnover
number (TON) reaching approximately 500.
First, the oxidation of secondary amines to nitrones was
examined. In a control experiment, it was ascertained that
the oxidation of dibenzylamine (2a) with H2O2 in the ab-
sence of 1 did not proceed. On the other hand, the reaction
in the presence of 2 mmole equivalents of 1 gave the
corresponding nitrone (3a) in 86% yield (Table 1, entry
1).6–8 It was attained with 2.5% hydrogen peroxide under
organic solvent-free conditions at room temperature. The
reaction of substituted dibenzylamine, bis[(4-trifluoro-
methyl)benzyl]amine (2b), proceeded smoothly to afford
3b in 90% yield with the turnover number (TON) of 1
reaching 450. Moreover, regioselective oxidations of
bis(p-substituted benzyl)amines resulted in that the depro-
tonation took place at more acidic benzylic position to af-
ford the nitrones in 71–94% yield (regioselectivity: 1.3:1–
1.7:1) (entries 3–5). No isomerization between 3c and 3c
was confirmed by the reaction of 3c or 3c in the presence
of 1 and 2.5% H2O2. Thus, it was secured that the regio-
selectivity of nitrones was determined at the oxidation
stage of a dibenzyl hydroxylamine to nitrones.9
So far, immobilized oxidation catalysts have been devel-
oped which were supported by cross-linked polystyrene
resins, silica gels and metal oxides. Unfortunately, they
often result in lower catalytic activity compared with their
soluble counterparts, and are sometimes obliged to use
harmful organic solvents.3,4 To overcome the limitation, a
novel methodology for creating insoluble and highly ac-
tive catalysts is needed.
For the reasons mentioned above, we decided to focus on
a self-assembled process between non-cross-linked poly-
mer ligands and an inorganic species.5 One example is
that we developed a highly reactive insoluble tungsten
catalyst 1 which was formed from phosphotungstic acid
and poly(N-isopropylacrylamide) with an ammonium salt
(Figure 1).5a This catalyst, used in ppm molar equivalents,
promoted an efficient epoxidation of allylic alcohols with
hydrogen peroxide under organic solvent-free conditions.
Having got the successful results, we report here the ap-
plication of it to the oxidation of sulfides and amines. It is
noteworthy that the reaction can be also performed using
hydrogen peroxide without an organic solvent, and that
To examine the oxidation of a cyclic secondary amine, the
reaction of tetrahydroisoquinoline (2f) was performed,
furnishing 3f for the synthesis of isoquinoline alkaloids in
70% yield (entry 6).8b Furthermore, the catalytic system
was extended to the oxidation of primary amines to
oximes. The amines 2g and 2h can be converted to the
corresponding oximes 3g and 3h in moderate yields (en-
tries 7 and 8).
Synlett 2002, No. 12, 02 12 2002. Article Identifier:
1437-2096,E;2002,0,12,2031,2034,ftx,en;U08702ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

2032
Y. M. A. Yamada et al.
LETTER
Table 1 Synthesis of the Nitrones and the Oximes by Oxidation of the Amines Promoted by Catalyst 1 with Hydrogen Peroxidea
Entry
1
Substrate
Time (h)
24
Product
Yield (%)
86
N
H
N+
O-
2a
3a
2
3
4
24
24
24
90
N
N+
O-
H
F3C
CF3
F3C
CF3
2b
3b
94 (3c/3c = 1.7/1)
80 (3d/3d = 1.3/1)
N
N+
O-
H
MeO
CF3
MeO
CF3
2c
3c
N
H
N+
O-
CF3
CN
CF3
CN
2d
3d
3e
5b
24
12
71 (3e/3e = 1.5/1)
N
H
N+
O-
2e
2f
6
70
N+
NH
O-
3f
7c
8
24
3
65
62
NOH
NH2
3g
2g
2h
NH2
NOH
3h
N+
O-
N+
O-
N+
O-
3c'
MeO
3d'
3e'
CF3
CF3
CN
a Catalyst 1 (2 mmole equiv), 2.5% hydrogen peroxide (3 mole equiv) at r.t.
b The reaction was performed at 40 °C.
c The reaction was performed at 0 °C.
At this point, we turned our attention to the oxidation of corresponding sulfones in high yields (84–90%) (entries
sulfides to sulfones (Table 2).10,11 In a control experiment, 2–5). Similarly, the chemoselective oxidation of meth-
it was confirmed that the reaction of thioanisole (4a) with- ylthio benzothiazole (4f) that is the useful nucleophile for
out 1 afforded the corresponding sulfone 6a, albeit in 26% the Julia olefination14 afforded the sulfone 6f in 78% yield
yield. Although the oxidation of the sulfides 4a–j was (entry 6). In this reaction, benzothiazole ring was unaf-
tested without 1, the corresponding sulfones were ob- fected under the condition. It was notable that the oxida-
tained only in trace amounts (6j) up to 33% yield (6e) as tion of alkyl thiophenols (4g–4j) also resulted in 6g–6j in
depicted in Table 2. On the other hand, the reaction of 4a high yields (entries 7–10). Especially, chemoselective ox-
in the presence of 2 mmol equivalents of 1 proceeded idations of 4h and 4i proceeded efficiently to give 6h and
smoothly to provide 6a in 97% yield with the TON of this 6i in high yields, where the olefin and alcohol were toler-
catalyst reaching approximately 500 (entry 1).12,13 In the ated and -elimination of the alcohol was not observed
oxidation to the sulfones, organic solvent-free conditions (entries 8 and 9). The sulfide with a cyclic acetal 4j was
using aqueous hydrogen peroxide were also effective. The converted to 6j in 71% yield, which was the substrate in
substituted aryl methyl sulfides were also converted to the the preparation of the prostaglandin analogue.15
Synlett 2002, No. 12, 2031–2034 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Oxidation of Amines and Sulfides
2033
Table 2 Oxidation of Alkyl Aryl Sulfides to Sulfones Promoted by
Catalyst 1 with H2O2
Table 3 The Oxidation of 4a to 6a Promoted by Recycled 1
1 ( 2x10-3 mol eq )
catalyst 1
PhSO2Me
PhSMe
( 2x10-3 mol eq )
40% aq H2O2 ( 3 mol eq )
ArSR1
ArSOR1
ArSO2R1
+
4a
6a
50 °C, 4 h
35-40% aq H2O2
(4 mol eq)a
4a-j
5a-j
6a-j
Entry
Catalyst
1st use
2nd use
3rd use
4th use
5th use
Yield (%)
50 °C, 4 hb
1
2
3
4
5
97
86
83
88
82
Entry
1
4
Catalyst 5 (%)c
6 (%)c
PhSMe (4a)
1
3
97
–
(74)
(26)
2
3
4
5
6
p-Me-C6H4SMe (4b)
p-Br-C6H4SMe (4c)
p-MeO-C6H4SMe (4d)
p-CHO-C6H4SMe (4e)
1
–
9
(71)
90
(22)
1
–
12
(70)
87
(15)
should be supported that phosphotungstate in 1 main-
tained the heteropolyacidic structure such as the Keggin
type (PW12O403–).17 In addition, the catalyst that was
recovered after the oxidation also showed a broad peak at
–13 ppm. This result indicated that the structure of 1 was
unchanged during the oxidation.18
1
–
6
(76)
84
(24)
1
–
–
(53)
86
(33)
1
–
17
(9)
78
(0)
N
In conclusion, the oxidations of sulfides and amines with
hydrogen peroxide using the tungsten-polymer assembled
catalyst were performed under organic solvent-free condi-
tions, and the catalyst was reused five times. Since the
reaction system itself represented great potential and
could be promoted by ppm molar equivalents of catalysts,
optimization of this catalyst and application to asymmet-
ric catalysis is currently under study.
SMe
S
(4f)
7
8
PhSEt (4g)
1
–
3
(75)
91
(17)
1
–
3
(80)
81
(10)
PhS
(4h)
9
1
–
–
(80)
Quant.
(13)
OH
PhS
Acknowledgment
(4i)
We thank Ms. Junko Shimode and Ms. Maroka Kitsukawa for spec-
troscopic measurement. This work was partially supported by a
Grant-in-Aid for Scientific Research from the Ministry of Educati-
on, Science and Technology. Y. M. A. Y. thanks the Inoue Found-
ation for Science (IFS) for the Inoue Research Award for Young
Scientists, and Dainippon Ink and Chemicals, Inc. for its Award in
Synthetic Organic Chemistry, Japan.
10
1
–
11
(54)
71
(trace)
O
O
PhS
(4j)
a In entry 1, 3 mol equiv of H2O2 was used.
b In entries 6 and 8, the reaction time was 7 h.
c The yields of the oxidations without 1 are in parentheses.
References
Furthermore, we evaluated the catalytic activity of the re-
covered 1 (Table 3): when the oxidation of 4a was per-
formed at 50 °C for 4 h using 2 mmole equivalents of 1,
6a was given in 97% yield (entry 1). In the repeated use of
the recovered catalyst, 6a was obtained in 86% yield (en-
try 2). Again, the recovered catalyst was reused; that is,
the third, fourth and fifth reactions afforded 6a in 83%,
88%, and 82% yield, respectively (entries 3–5).
(1) For reviews, see: (a) Catalytic Oxidation: Principles and
Applications; Sheldon, R. A.; van Santen, R. A., Eds.; World
Scientific Publishing: London, 1995. (b) Ward, R. S.;
Diaper, R. L. Sulfur Rep. 2001, 22, 251. (c) Jackson, D. A.;
Rawlinson, H.; Barba, O. Spec. Pub.-Royal Soc. Chem.
2001, 260, 47. (d) Mashkina, A. V. Sulfur Rep. 1991, 10,
279. (e) Torssell, K. B. G. Nitrile Oxides, Nitrones, and
Nitronates in Organic Synthesis; Wiley: New York, 1988.
(f) Lund, H.; Hammerich, O. Org. Electrochem. 2001, 545.
(2) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory
and Practice; Oxford Univ. Press: Oxford, 1998. (b) Green
Chemical Syntheses and Processes: Recent Advances in
Chemical Processing; Anastas, P. T.; Heine, L. G.;
Williamson, T. C., Eds.; ACS: Ohio, 2001. (c) Tundo, P.;
Anastas, P.; Black, D. S.; Breen, J.; Collins, T.; Memoli, S.;
Miyamoto, J.; Polyakoff, M.; Tumas, W. Pure Appl. Chem.
2000, 72, 1207.
We have already analyzed 1 by scanning electron micro-
scope (SEM), elementary analysis and infrared spectros-
copy.5a To obtain further information on the structure of
the catalyst, we analyzed 1 by gel-phase 31P NMR in D2O.
The broad peak of 1 was detected at –13 ppm. Since it was
reported that the signals of H3PW12O40 and [ -
C5H5N(CH2)15CH3]3PW12O40 were observed at the similar
frequency (–14.7 ppm16 and –14.5 ppm11b respectively), it
(3) For reviews, see: (a) Centi, G.; Cavani, F.; Trifiro, F.
Selective Oxidation by Heterogeneous Catalysis:
Synlett 2002, No. 12, 2031–2034 ISSN 0936-5214 © Thieme Stuttgart · New York

2034
Y. M. A. Yamada et al.
LETTER
(10) General procedure for the oxidation of sulfides to
Fundamental and Applied Catalysis; Kluwer Academic
Pubs: Norwell, MA, 2000. (b) Hodnett, K. Heterogeneous
Catalytic Oxidation; Wiley: New York, 2000.
sulfones catalyzed by catalyst 1: The mixture of 1, 4 and
35–40% H2O2 aqueous solution was shaken by PetiSyther®
(Shimadzu Scientific Research Inc. Japan) at 700 rpm at 50
°C for 4–7 h, it was diluted with EtOAc and filtered. To the
filtrate was added saturated Na2S2O3 and brine, and it was
extracted with EtOAc ( 3), dried over Na2SO4, filtered,
dried in vacuo, and purified by column chromatography to
give the products. While the shaker (PetiSyther®) for solid-
phase syntheses was used in these reactions, the glassware
vessel equipped with a magnetic stirrer can be also used.
(11) For examples of the oxidation of sulfides to sulfones by
homogeneous tungsten catalysts, see: (a) Schultz, H. S.;
Freyermuth, H. B.; Buc, S. R. J. Org. Chem. 1963, 28, 1140.
(b) Ishii, Y.; Tanaka, H.; Nishiyama, Y. Chem. Lett. 1994, 1.
(c) Stec, Z.; Zawadiak, J.; Skibinski, A.; Pastuch, G. Polish
J. Chem. 1996, 70, 1121. (d) Neumann, R.; Juwiler, D.
Tetrahedron 1996, 52, 8781. (e) Gresley, N. M.; Griffith,
W. P.; Laemmel, A. C.; Nogueira, H. I. S.; Perkin, B. C. J.
Mol. Catal. 1997, 117, 185. (f) Collins, F. M.; Lucy, A. R.;
Sharp, C. J. Mol. Catal. 1997, 117, 397. (g) Yasuhara, Y.;
Yamaguchi, S.; Ichihara, J.; Nomoto, T.; Sasaki, Y.
Phosphorus Res. Bull. 2000, 11, 43. (h) Sato, K.; Hyodo,
M.; Aoki, M.; Zheng, X.-Q.; Noyori, R. Tetrahedron 2001,
57, 2469.
(4) For recent developments and improvements for the
oxidation of amines, see: (a) Reddy, J. S.; Jacobs, P. A. J.
Chem. Soc., Perkin Trans. 1 1993, 22, 2665. (b) Joseph, R.;
Sudalai, A.; Ravindranathan, T. Synlett 1995, 11, 1177.
(c) Joseph, R.; Ravindranathan, T.; Sudalai, A. Tetrahedron.
Lett. 1995, 36, 1903. (d) Delaude, L.; Laszlo, P. J. Org.
Chem. 1996, 61, 6360. (e) Dewkar, G. K.; Nikalje, M. D.;
Ali, I. S.; Paraskar, A. S.; Jagtap, H. S.; Sudalai, S. Angew.
Chem. Int. Ed. 2001, 40, 405. (f) For recent developments
and improvements for the oxidation of sulfides to sulfones,
see: Dell’Anna, M. M.; Mastrorilli, P.; Nobile, C. F. J. Mol.
Catal. A: Chem. 1996, 108, 57. (g) Alcon, M. J.; Corma, A.;
Iglesias, M.; Sanchez, F. J. Mol. Catal. A: Chem. 2002, 178,
253.
(5) (a) Yamada, Y. M. A.; Ichinohe, M.; Takahashi, H.;
Ikegami, S. Org. Lett. 2001, 3, 1837. (b) Yamada, Y. M. A.;
Ichinohe, M.; Takahashi, H.; Ikegami, S. Tetrahedron Lett.
2002, 43, 3431. (c) Yamada, Y. M. A.; Takeda, K.;
Takahashi, H.; Ikegami, S. Org. Lett. 2002, 4, 3371.
(6) General Procedure for the oxidation of amines catalyzed
by catalyst 1: To a suspension of 15a (40 mg; 5 µmol) and 2
(2.52 mmol) was added 2.5% H2O2 aqueous solution (7.56
mmol) dropwise for 50 min at 0 °C (entry 3: added dropwise
at r.t.; entry 5: added one portion at r.t.). The mixture was
stirred at room temperature (entry 5: 40 °C; entry 7: 0 °C) for
3–24 h, before it was diluted with EtOAc and filtered
through a glass filter. Brine was added to the filtrate, and it
was extracted with EtOAc ( 3). The extract was washed
with brine, dried over Na2SO4, filtered, dried in vacuo, and
purified by column chromatography to give 3.
(12) The reaction with 2.5% H2O2 proceeded slower (55 h) than
that with 35–40% H2O2, providing sulfone 6a in 95% yield.
(13) Noyori et al. reported that the oxidation of sulfides to
sulfoxides proceeded efficiently in hydrogen peroxide
without catalysts, so that we have not examined the selective
oxidation to sulfoxide. See ref.11h
(14) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron
Lett. 1991, 32, 1175.
(7) For examples of the oxidation of amines by homogeneous
tungsten catalysts; for a review, see: Herrmann, W. A.;
Fridgen, J.; Haider, J. J. Peroxide Chemistry; Adam, W.,
Ed.; Wiley: Weinheim, 2000, 406–432.
(8) For examples of the oxidation of amines by homogeneous
tungsten catalysts, see: (a) Ogata, Y.; Tomizawa, K.;
Maeda, H. Bull. Chem. Soc. Jpn. 1980, 53, 285.
(15) (a) Kondo, K.; Tunemoto, D. Tetrahedron Lett. 1975, 17,
1397. (b) Caton, M. P. L.; Coffee, E. C. J.; Watkins, G. L.
Tetrahedron Lett. 1972, 9, 773.
(16) Massart, R.; Contant, R.; Fruchart, J.-M.; Ciabrini, J.-P.;
Fournier, M. Inorg. Chem. 1977, 16, 2916.
(17) Keggin, J. F. Proc. R. Soc. London, Ser. A. 1934, 144, 75.
(18) (a) Brégault et al. reported that heteropolyacidic structure
easily decomposed in the presence of hydrogen peroxide
under the homogeneous conditions, see: Salles, L.; Aubry,
C.; Thouvenot, R.; Robert, F.; Dorémieux-Morin, C.;
Chottard, G.; Ledon, H.; Jeannin, Y.; Brégault, J. Inorg.
Chem. 1994, 33, 871. (b) On the other hand, Ishii et al.
proved that [ -C5H5N+(CH2)15CH3]3PW12O403– maintained
the structure closed to Keggin unit after treatment with
hydrogen peroxide. See ref.11b
(b) Murahashi, S.; Mitsui, H.; Shiota, T.; Tsuda, T.;
Watanabe, S. J. Org. Chem. 1990, 55, 1736. (c) Sakaue, S.;
Sakata, Y.; Ishii, Y. Chem. Lett. 1992, 289. (d) Marcantoni,
E.; Petrini, M.; Polimanti, O. Tetrahedron Lett. 1995, 36,
3561. (e) Ballistreri, F. P.; Barbuzzi, E. G. M.; Tomaselli, G.
A. J. Org. Chem. 1996, 61, 6381.
(9) The reaction of 2c was performed in CH2Cl2 (0.25 M) at
room temperature for 95 h, providing 3c and 3c in 95% yield
(3c/3c = 1.76:1). Even in the reaction of 3c or 3c with
CH2Cl2, isomerizations were hardly observed.
Synlett 2002, No. 12, 2031–2034 ISSN 0936-5214 © Thieme Stuttgart · New York