Recoverable, Reusable, Highly Active, and Sulfur-Tolerant Polymer Incarcerated Palladium for Hydrogenation

Article abstract of DOI:10.1021/jo0358527

A new type of immobilized palladium, PI (polymer incarcerated) Pd (2b), from Pd(PPh₃)₄ and copolymer (1b) has been developed. The excellent activity of PI Pd has been demonstrated in hydrogenation of various olefins, benzyl ethers, and nitro and aromatic compounds. PI Pd is tolerant under high pressure and high temperature and can be recovered and reused several times without loss of activity even under harsh conditions. Moreover, PI Pd is highly resistant to poisoning by sulfur.

Full text of DOI:10.1021/jo0358527

Recover a ble, Reu sa ble, High ly Active, a n d
Su lfu r -Toler a n t P olym er In ca r cer a ted
P a lla d iu m for Hyd r ogen a tion
Kuniaki Okamoto, Ryo Akiyama, and Shuj Kobayashi*
Graduate School of Pharmaceutical Sciences, The University
of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, J apan
skobayas@mol.f.u-tokyo.ac.jp
Received December 21, 2003
Abstr a ct: A new type of immobilized palladium, PI (poly-
mer incarcerated) Pd (2b), from Pd(PPh3)4 and copolymer
(1b) has been developed. The excellent activity of PI Pd has
been demonstrated in hydrogenation of various olefins,
benzyl ethers, and nitro and aromatic compounds. PI Pd is
tolerant under high pressure and high temperature and can
be recovered and reused several times without loss of activity
even under harsh conditions. Moreover, PI Pd is highly
resistant to poisoning by sulfur.
F IGURE 1. Compounds 1-4.
temperature. We decided to modify the structure of PI
Pd (2a ) and now report here a new type of highly active
and versatile PI Pd, which has high resistance to harsh
conditions and poisoning by sulfur in various hydrogena-
tions.
Palladium-catalyzed hydrogenation is frequently used
not only in laboratories but also in industry. While
immobilized palladium catalysts such as Pd/C and Pd/
Al2O3, etc. have been often employed, leaching of the
palladium from the supports, moderate yields of recovery,
contamination of the palladium to products, and poison-
ing by sulfur are sometimes serious problems especially
in the manufacture of pharmaceuticals.1
We have recently developed the polymer-incarcerated
(PI) method2 to immobilize metal catalysts onto poly-
mers.3 The method is based on microencapsulation4 and
cross-linking, and Pd(PPh3)4 was immobilized using this
method to form polymer-incarcerated palladium (PI Pd).
It was revealed that PI Pd (2a ) derived from polymer (1a )
consisted of phosphine-free palladium(0) and effectively
catalyzed hydrogenation of olefins in THF under atmo-
spheric pressure. Moreover, the catalyst was recovered
completely by simple filtration and could be reused
several times without loss of activity. On the other hand,
it was assumed that the benzyl ether moieties of PI Pd
(2a ) would be cleaved in the hydrogenation under harsh
conditions, such as high hydrogen pressure and high
We designed a new copolymer (1b) for higher resistant
PI Pd (2b), which has no benzylic ether moiety. Copoly-
mer (1b) was synthesized by radical copolymerization of
styrene, epoxide monomer (3), and tetraethyleneglycol
monomer (4) (Figure 1).5 PI Pd (2b) was prepared from
Pd(PPh3)4 and polymer (1b) according to the method for
the preparation of 2a .2,5 First, we examined the catalytic
activity and the effect of loading levels5,6 of 2a and 2b in
the hydrogenation of benzalacetone and cholesterol under
atmospheric pressure (Tables 1 and 2). It was revealed
that the activity of 2b was almost the same as that of 2a
in the hydrogenation of benzalacetone, while 2b exhibited
higher activity than 2a in the reduction of cholesterol, a
more hindered substrate. We also confirmed that the
loading level of the palladium did not affect the activity
of either PI Pd catalyst.
Several other substrates were hydrogenated using PI
Pd (2b), and the results are summarized in Table 3. In
addition to normal C-C double and triple bonds, benzyl
ethers, nitrobenzene, and quinoline were easily hydro-
genated under atmospheric pressure at room tempera-
ture. We also applied PI Pd (2b) to the reduction of less
reactive substrate 7, which is the intermediate for the
synthesis of an antidiabetic agent, pioglitazone (8). This
agent is expected to effectively ameliorate the abnormal
glucose and lipid metabolism associated with noninsulin
dependent diabetes mellitus or obesity.7 It is known that
the yields of the hydrogenation of 7 using conventional
(1) (a) Trimm, D. L. Design of Industrial Catalysts; Elsevier:
Amsterdam, 1980. (b) Rylander, P. N. Hydrogenation Methods; Aca-
demic Press: New York, 1985. (c) Satterfield, C. N. Heterogeneous
Catalysis in Industrial Practice, 2nd ed.; McGraw-Hill: New York,
1991.
(2) Akiyama, R.; Kobayashi, S. J . Am. Chem. Soc. 2003, 125, 3412.
(3) For recent reviews of polymer-supported metal catalysts, see:
(a) Corain, B.; Centomo, P.; Lora, S.; Kralik, M. J . Mol. Catal. A: Chem.
2003, 755. (b) Karakhanov, E. A.; Maximov, A. L. Met. Complexes Met.
Macromol. 2003, 457. (c) Leadbeater, N. E.; Marco, M. Chem. Rev.
2002, 102, 3217. (d) Stefan, B.; J ohannes, K.; Nils, G. Handb.
Organopalladium Chem. Org. Synth. 2002, 2, 3031. (e) Kralik, M.;
Biffis, A. J . Mol. Catal. A: Chem. 2001, 177, 113.
(4) (a) Kobayashi, S.; Nagayama, S. J . Am. Chem. Soc. 1998, 120,
2985. (b) Nagayama, S.; Endo, M.; Kobayashi, S. J . Org Chem. 1998,
63, 6094. (c) Kobayashi, S.; Endo, M.; Nagayama, S. J . Am. Chem. Soc.
1999, 121, 11229. (d) Kobayashi, S.; Ishida, T.; Akiyama, R. Org. Lett.
2001, 3, 2649. (e) Akiyama, R.; Kobayashi, S. Angew. Chem., Int. Ed.
2001, 40, 3469. (f) Akiyama, R.; Kobayashi, S. Angew. Chem., Int. Ed.
2002, 41, 2602.
(5) Details are shown in the Supporting Information.
(6) The loading level of the palladium was determined by XRF
analysis.
(7) (a) Sohda, T.; Momose, Y.; Meguro, K.; Kawamatsu, Y.; Sug-
iyama, Y.; Ikeda, H. Arzneim-Forsch. 1990, 40, 37. (b) Sugiyama, Y.;
Taketomi, S.; Shimura, Y.; Sohda, T.; Meguro, K.; Fujita, T. Arzneim-
Forsch. 1990, 40, 253. (c) Sugiyama, Y.; Shimura, Y.; Ikeda, H.
Arzneim-Forsch. 1990, 40, 436.
10.1021/jo0358527 CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/10/2004
J . Org. Chem. 2004, 69, 2871-2873
2871

TABLE 1. Hyd r ogen a tion of Ben za la ceton e Usin g P I P d
TABLE 3. Hyd r ogen a tion of Sever a l Su bstr a tes Usin g
2ba
loading level
of Pd (mmol/g)
entry
PI Pd
yielda (%)
1
2
3
2a
2b
2b
0.108
0.091
0.707
85
85
87
a
Isolated yield (the ratio of 5/6 ) 95/5).
TABLE 2. Hyd r ogen a tion of Ch olester ol Usin g P I P d
loading level
of Pd (mmol/g)
entry
PI Pd
yielda (%)
a
1
2
3
4
2a
2a
2b
2b
0.108
0.813
0.090
0.593
63
69
85
85
All reactions were carried out using 5 mol % of 2b (the loading
level of the palladium was 0.707 mmol/g) in THF under atmo-
spheric H2 pressure at rt. The leaching of the palladium to reaction
mixture was measured by XRF analysis. No peaks of the palladium
were detected in all entries. Isolated yield. c Determined by GC
b
Determined by 1H NMR analysis.
a
analysis.
SCHEME 1. Hyd r ogen a tion for An tid ia betic Agen t
Usin g 2ba
catalysts are not satisfactory probably because this
substrate has catalytic poisonous nitrogen and sulfur
moieties in the molecule.8 The hydrogenation of 7 using
PI Pd (2b) under atmospheric pressure proceeded smoothly
to afford 8 quantitatively (Scheme 1). No contamination
of the palladium was detected by X-ray fluorescence
(XRF) analysis,9 and PI Pd (2b) could be recovered and
reused. On the other hand, phenanhrene and 2-methox-
ynaphthalene were hydrogenated under 70 atm of hy-
drogen pressure at 50 °C (Scheme 2 and Table 4). PI Pd
(2b) was successfully recovered and reused even under
high hydrogen pressure at elevated temperature without
loss of activity, and leaching of the palladium was not
detected by XRF analysis in all runs.
Furthermore, a remarkable result was obtained in the
hydrogenation of benzothiophene. In the petrochemical
industry, the hydrotreating of petroleum feedstocks is
conducted in refineries, and sulfur compounds are con-
verted to hydrocarbons and H2S via a hydrodesulfuriza-
tion (HDS) process. Among the sulfur compounds,
thiophenes are quite abundant and benzothiophene is one
of the most difficult to degrade.10 The HDS process is
a
(a) The loading level of the palladium was 0.593 mmol/g. (b)
Isolated yield.
typically performed at high hydrogen pressures (>200
atm) and temperatures (300-450 °C) in the presence of
sulfided metal-based catalysts such as nickel- and cobalt-
promoted MoS2 and WS2 supported on alumina, and
benzothiophene is hydrogenated to dihydrobenzothiophene
during the HDS process.11 It is noted that the hydrogena-
(8) Momose, Y.; Meguro, K.; Ikeda, H.; Hatanaka, C.; Oi, S.; Shoda,
T. Chem. Pharm. Bull. 1991, 39, 1440.
(9) The lower limit is <5 ppm.
(10) Highly active homogeneous ruthenium catalysts for HDS have
been reported. (a) Borowski, F. A.; Sabo-Etienne, S.; Donnadieu, B.;
Chaudret, B. Organometallics 2003, 22, 4803. (b) Bianchini, C.; Meli,
A.; Moneti, S.; Oberhauser, W.; Vizza, F.; Herrera, V.; Fuentes, A.;
Sanchez-Delgado, R. A. J . Am. Chem. Soc. 1999, 121, 7071. (c) Rojas,
I.; L. Linares, F.; Valencia, N.; Bianchini, C. J . Mol. Catal, 1999, 144,
1.
(11) (a) Topsφe, H.; Clause, B. S.; Massoth, F. E. Hydrotreating
Catalysis; Springer-Veralag: Berlin, 1996. (b) Scherzer, J .; Gruia, A.
J . Hydrocracking Science and Technology; Marcel Dekker: New York,
1996. (c) Gates, B. C.; Catalytic Chemistry; J ohn Wiley: New York,
1992; Chapter 5, p 390. (d) Whitehurst, D. D.; Isoda, T.; Mochida, I.
Adv. Catal. 1998, 42, 345. (e) van den Berg, J . P.; Lucien, J . P.;
Germaine, G.; Thielemans, G. L. B. Fuel Process Technol. 1993, 35,
119. (f) Prins, R.; de Beer, V. H. J .; Somorjai, G. A. Catal. Rev.-Sci.
Eng. 1989, 31, 1.
2872 J . Org. Chem., Vol. 69, No. 8, 2004

SCHEME 2. Hyd r ogen a tion of P h en a n th r en e
Usin g 2ba
SCHEME 3. Hyd r ogen a tion of Ben zoth iop h en e
Usin g 2ba
a
(a) The loading level of the palladium was 0.707 mmol/g. (b)
Isolated yield. No leaching of the palladium to the reaction mixture
was detected.
a
(a) The loading level of the palladium was 0.707 mmol/g. (b)
The ratio of 9/10/11 was determined by 1H NMR. No leaching of
Pd (2b) has been shown in hydrogenation of various
olefins, benzyl ethers, and nitro and aromatic compounds.
PI Pd (2b) was tolerant under high pressure and high
temperature and could be recovered and reused several
times without loss of activity even under harsh condi-
tions. It is noted that PI Pd is highly resistant to
poisoning by sulfur.
the palladium to the reaction mixture was detected.
TABLE 4. Reu se of 2b u n d er Ha r sh Con d ition s
Exp er im en ta l Section
recovery
run
yieldb (%)
ratio of 12/13c
of 2b (%)
A Typ ica l Exp er im en ta l P r oced u r e for th e Hyd r ogen a -
tion . PI Pd (2b, 0.025 mmol, 5 mol %) and 2-methoxynaphtha-
lene (79.1 mg, 0.50 mmol) were combined in ethanol (7 mL). The
mixture was stirred for 18 h at 50 °C under 70 atm of hydrogen
pressure. The catalyst was filtered and washed with tetrahy-
drofuran, and the solvents of the filtrate were removed under
reduced pressure. The residue was purified by PTLC to afford a
mixture of 5,6,7,8-tetrahydro-2-methoxynaphthalene (12) and
1,2,3,4-tetrahydro-2-methoxynaphthalene (13) (81.1 mg, conver-
sion 100%, 12/13 ) 73/27). Recovered PI Pd was dried under
reduced pressure and reused.
1
2
3
4
5
100
100
100
99
73/27
74/26
74/26
74/26
74/26
quant
quant
quant
quant
quant
100
a
All reactions were carried out using 5 mol % of 2b (the loading
level of the palladium was 0.707 mmol/g) in THF under atmo-
spheric H2 pressure at rt. The leaching of the palladium to reaction
mixture was measured by XRF analysis. No peaks of the palladium
were detected in all entries. Isolated yield. c Determined by GC
b
analysis.
tion of benzothiophene using PI Pd (2b) under milder
conditions compared to HDS conditions proceeded in
excellent yield (Scheme 3).12 The excellent activity of PI
Pd (2b) is possibly due to the highly dispersed palladium
in the polymer, and the surrounding benzene rings of the
polymer may protect the palladium from poisoning by
sulfur.
Ack n ow led gm en t. This work was partially sup-
ported by CREST and SORST, J apan Science Technol-
ogy Agency (J ST), and a Grant-in-Aid for Scientific
Research from the J apan Society of the Promotion of
Sciences (J SPS).
In summary, we have prepared a new type of PI Pd
(2b) from Pd(PPh3)4 and 1b. The excellent activity of PI
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal information and experimental details and spectral data for
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) It was confirmed that catalytic activity of 2b was higher than
that of Pd/C (5% Pd/C gave the reduced product in 14% yield, 54%
yield was obtained using PI Pd (2b) under the same conditions (10
atm, 140 °C for 24 h in THF).
J O0358527
J . Org. Chem, Vol. 69, No. 8, 2004 2873