Efficient heterogeneous oxidation of alkylarenes with molecular oxygen

Article abstract of DOI:10.1021/ol0485363

(Chemical Equation Presented) Ru(OH)_x/Al₂O ₃ efficiently catalyzes the heterogeneous aerobic oxygenation or oxidative dehydrogenation of alkylarenes to give the corresponding oxygenated or dehydrogenated products. Catalyst/product separation is very easy, and the recovered catalyst is reusable with retention of the high catalytic performance.

Full text of DOI:10.1021/ol0485363

ORGANIC
LETTERS
2004
Vol. 6, No. 20
3577-3580
Efficient Heterogeneous Oxidation of
Alkylarenes with Molecular Oxygen
‡
‡
Keigo Kamata,† Jun Kasai,‡ Kazuya Yamaguchi,†, and Noritaka Mizuno*,†,
Core Research for EVolutional Science and Technology, Japan Science and
Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan, and
Department of Applied Chemistry, School of Engineering, The UniVersity of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan
tmizuno@mail.ecc.u-tokyo.ac.jp
Received July 27, 2004
ABSTRACT
Ru(OH)x/Al2O3 efficiently catalyzes the heterogeneous aerobic oxygenation or oxidative dehydrogenation of alkylarenes to give the corresponding
oxygenated or dehydrogenated products. Catalyst/product separation is very easy, and the recovered catalyst is reusable with retention of the
high catalytic performance.
The oxidation of alkylarenes has received much attention.
For example, it has been reported that the polyacene
derivatives can be applied to organic semiconductors and
transistors1 and that dehydrogenation of the corresponding
alkylarenes is one of the most reliable candidates for the
synthesis of polyacene derivatives among various synthetic
procedures.2 Since dehydrogenation of alkylarenes typically
requires stoichiometric oxidation reagents and/or relatively
forced reaction conditions,3 alternative efficient procedures,
i.e., catalytic aerobic oxidation systems, have been desired.4
The development of the catalytic oxygenation of alkylarenes
with molecular oxygen is also technologically and environ-
mentally important. Although numerous catalytic systems
using nitrous oxide,5 sulfoxide,6 and molecular oxygen in
combination with reducing agents7 or radical initiators8 have
been reported, there are only a few examples of such liquid-
phase oxidation with molecular oxygen as the sole oxidant.9
In addition, the use of solid or supported catalysts is more
desirable because of their easy isolation from the products
and recycling.10 In these contexts, it is desirable to develop
the heterogeneously catalyzed aerobic oxidation of alkyl-
arenes with high turnover numbers under mild reaction
conditions. We report in this paper the efficient heteroge-
neous aerobic oxygenation and oxidative dehydrogenation
of alkylarenes catalyzed by Ru(OH)x/Al2O3.
(5) (a) Ben-Daniel, R.; Neumann, R. Angew. Chem., Int. Ed. 2003, 42,
92. (b) Hashimoto, K.; Tanaka, H.; Ikeno, T.; Yamada, T. Chem. Lett. 2002,
582.
(6) Khenkin, A. M.; Neumann, R. J. Am. Chem. Soc. 2002, 124, 4198.
(7) Maikap, G. C.; Guhathakurta, D.; Iqbal, J. Synlett 1995, 189.
(8) Ishii, Y.; Nakayama, K.; Takeno, M.; Sakaguchi, S.; Iwahama, T.;
Nishiyama, Y. J. Org. Chem. 1995, 60, 3934.
(9) (a) Khenkin, A. M.; Weiner, L.; Wang, Y.; Neumann, R. J. Am. Chem.
Soc. 2001, 123, 8531. (b) Feldman, D.; Rabinovitz, M. J. Org. Chem. 1988,
53, 3779. (c) Matsushita, T.; Ebitani, K.; Kaneda, K. Chem. Commun. 1999,
265. (d) Holliday, R. L.; Jong, B. Y. M.; Kolis, J. W. J. Supercrit. Fluids
1998, 12, 255.
(10) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: London, 1998. (b) Sheldon, R. A. Green
Chem. 2000, 2, G1. (c) Anastas, P. T.; Bartlett, L. B.; Kirchhoff, M. M.;
Williamson, T. C. Catal. Today 2000, 55, 11.
† Japan Science and Technology Agency.
‡ The University of Tokyo.
(1) (a) Scho¨n, J. H.; Kloc, Ch.; Bucher, E.; Batlogg, B. Nature 2000,
403, 408. (b) Dimitrakopoulos, C. D.; Purushothaman, S.; Kymissis, J.;
Callegari, A.; Shaw, J. M. Science 1999, 283, 822. (c) Afzali, A.;
Dimitrakopoulos, C. D.; Breen, T. L. J. Am. Chem. Soc. 2002, 124, 8812.
(2) Fu, P. P.; Harvey, R. G. Chem. ReV. 1978, 78, 317.
(3) (a) Nagano, T.; Yokoohji, K.; Hirobe, M. Tetrahedron Lett. 1984,
25, 965. (b) Wang, K.; Mayer, J. M. J. Am. Chem. Soc. 1997, 119, 1470.
(c) Lockwood, M. A.; Blubaugh, T. J.; Collier, A. M.; Lovell, S.; Mayer,
J. M. Angew. Chem., Int. Ed. 1999, 38, 225. (d) Takahashi, T.; Kitamura,
M.; Shen, B.; Nakajima, K. J. Am. Chem. Soc. 2000, 122, 12876.
(4) (a) Tanaka, H.; Ikeno, T.; Yamada, T. Synlett 2003, 576. (b)
Nakamichi, N.; Kawabata, H.; Hayashi, M. J. Org. Chem. 2003, 68, 8272.
10.1021/ol0485363 CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/03/2004

Table 1. Oxidation of Xanthene and 9,10-Dihydroanthracene with Molecular Oxygen by Various Catalystsa
xanthene 9,10-dihydroanthracene
conversion
(%)
selectivityb
(%)
conversion
(%)
selectivityc
(%)
entry
catalyst
1
2
3
4
5
6
7
8
9
10
11d
12d
13e
14e
15f
16f
17f
18f
19f
20f
Ru(OH)x/Al2O3
Ru(OH)3‚nH2O
RuO2
RuCl2(PPh3)3
RuCl2(DMSO)4
RuCl2(bpy)2
RuCl3‚nH2O
[Ru3O(OAc)6(H2O)3](OAc)
K2RuCl6
nPr4NRuO4
>99
<1
<1
<1
<1
<1
<1
<1
<1
38
<1
<1
6
3
2
2
1
<1
<1
2
>99
>99
37
9
<1
58
<1
4
<1
15
9
<1
<1
6
<1
5
6
21
11
<1
2
93
92
99
90
98
96
82
>99
Al2O3
Al2O3 treated with NaOH
Ru(OH)3‚nH2O + Al2O3
RuCl3‚nH2O + Al2O3
Pd(OH)x/Al2O3
Rh(OH)x/Al2O3
Pt(OH)x/Al2O3
V(OH)x/Al2O3
Fe(OH)x/Al2O3
Cu(OH)x/Al2O3
>99
>99
>99
>99
>99
54
84
19
79
97
>99
19
a Reaction conditions for xanthene: xanthene (1 mmol), catalyst (Ru: 2 mol %), PhCF3 (6 mL), 373 K, 2 h, under 1 atm of molecular oxygen. Reaction
conditions for 9,10-dihydroanthracene: 9,10-Dihydroanthracene (1 mmol), catalyst (Ru: 2 mol %), p-xylene (6 mL), 403 K, 4 h, under 1 atm of molecular
oxygen. Conversion and selectivity were determined by GC with an internal standard. b Selectivity for xanthen-9-one. c Selectivity for anthracene. Anthraquinone
and anthrone were formed as byproducts in some cases. d 80 mg. e Mixture of Ru catalyst (2 mol %) and Al2O3 (80 mg) was used. f Catalyst (metal: 2 mol
%).
First, the catalytic activity for the oxidation of xanthene
and 9,10-dihydroanthracene with 1 atm of molecular oxygen
as the sole oxidant was compared with those of various
catalysts (Table 1).11 No oxidation proceeded in the presence
of Al2O3 or Al2O3 treated with NaOH. The catalytic activity
of Ru(OH)x/Al2O3 was higher than those of other hetero-
geneous ruthenium catalysts such as Ru(OH)3‚nH2O, RuO2,
and zerovalent Ru clusters and homogeneous ruthenium
complexes. Under the same conditions, other supported
transition metal hydroxide catalysts of Pd, Rh, Pt, V, Fe,
and Cu were much less active. The catalytic activities of
Ru(OH)3‚nH2O and Al2O3 or RuCl3‚nH2O and Al2O3 were
lower than that obtained with Ru(OH)x/Al2O3. The oxidation
of xanthene in nonpolar p-xylene, trifluorotoluene, chloro-
benzene, and toluene for 1 h gave xanthen-9-one yields of
80, 78, 77, and 72%, respectively, under the conditions in
Table 1. The polar 1,4-dioxane, N,N-dimethylformamide,
acetonitrile, and acetic acid were poor solvents.
could be easily separated from the reaction mixture by simple
filtration. It was confirmed by inductively coupled plasma
combined with atomic emission spectroscopy (detection limit
of 7 ppb) that no ruthenium was present in the filtrate after
the separation of the catalyst. Then, the filtrate was evapo-
rated in vacuo, and the crude product was purified by
recrystallization to give analytically pure white crystals of
xanthen-9-one (92% isolated yield). Interestingly, the oxida-
tion of xanthene was completely stopped by the removal of
Ru(OH)x/Al2O3 from the reaction solution (Figure S1,
Supporting Information). A first-order dependence of the
initial rate on the amount of Ru(OH)x/Al2O3 (0.5-2.0 mol
%, Figure S3, Supporting Information) was observed. These
results indicate that any ruthenium species that leached into
the reaction solution was not an active homogeneous catalyst
and that the observed catalysis was truly heterogeneous in
nature.12 Further, recovered Ru(OH)x/Al2O3 after the oxida-
tion was recyclable, and both the reaction rate and selectivity
toward oxygenation and dehydrogenation were retained
(entries 2 and 13 in Table 2).
When the oxidation of xanthene was carried out at 373 K
in trifluorotoluene, a quantitative yield of xanthen-9-one was
obtained after 2 h. After the oxidation, the Ru(OH)x/Al2O3
The scope of the present Ru(OH)x/Al2O3 catalyst system
toward various kinds of alkylarene derivatives was examined.
The results are summarized in Table 2. In the present system,
monoactivated substrates such as toluene and xylene could
not be oxidized. In the case of substrates with only one
benzylic methylene group such as xanthene and fluorene,
(11) Typical Procedure for Oxidation. Into a glass vial were succes-
sively placed Ru(OH)x/Al2O3 (2 mol % Ru), xanthene (1 mmol), and PhCF3
(6 mL). The reaction mixture was stirred at 373 K under 1 atm of molecular
oxygen. The products were confirmed by GC analysis in combination with
1
mass and H and 13C NMR spectroscopy, and the conversion and product
selectivity were periodically determined by GC analysis during the oxidation.
After the reaction was finished, the spent catalyst was separated by filtration,
washed with a large amount of acetone, and dried in vacuo prior to being
recycled.
(12) Sheldon, R. A.; Wallau, M.; Arends, I. W. C. E.; Schuchardt, U.
Acc. Chem. Res. 1998, 31, 485.
3578
Org. Lett., Vol. 6, No. 20, 2004

to the corresponding anthracenes together with small amounts
of the ketones (entries 5-7). Not only benzylic C-H bonds
but also allylic C-H bonds were also efficiently dehydro-
genated to afford the corresponding aromatized products
(entries 9 and 10). Heterocyclic amines, 1,2,3,4-tetrahydro-
quinoline, and indoline gave the corresponding dehydroge-
nated products (entries 11 and 12). Remarkably, the N-pro-
tected indoline of N-benzylindoline was dehydrogenated to
N-benzylindole with protection of benzyl group (entry 14).
The rates of alcohol oxidations were much faster than those
of the oxidation of alkylarenes to the ketones. For example,
the oxidation rate of fluoren-9-ol to fluoren-9-one at 403 K
was 8.23 mM min-1 and was 20 times faster than that of
fluorene to fluoren-9-one. When the reaction of 9-hydroxy-
9,10-dihydroanthracene was carried out under reaction
conditions C in Table 2, 9-hydroxy-9,10-dihydroanthracene
was quantitatively converted within 10 min, and anthracene,
anthrone, and anthraquinone were obtained in 91, 7, and 2%
yields, respectively.13 Al2O3 could also efficiently catalyze
the dehydration of 9-hydroxy-9,10-dihydroanthracene to give
99% yield of anthracene as the sole product under the same
reaction conditions,13 suggesting that the dehydration may
mainly be promoted by the Al2O3 support. Further, it was
confirmed that Ru(OH)x/Al2O3 did not catalyze the oxidation
of anthracene to anthrone and anthraquinone. These facts
suggest that alcohols are formed as intermediate products
that are rapidly dehydrogenated or dehydrated to the corre-
sponding oxygenated or dehydrogenated products, respec-
tively, in the present alkylarene oxidation.
Table 2. Oxidation of Various Alkylarene Derivatives with
Molecular Oxygen Catalyzed by Ru(OH)x/Al2O3
a
The reaction rates and selectivities for the oxidation of
xanthene and 9,10-dihydroanthracene were not affected by
the addition of radical scavenger 2,6-di-tert-butyl-4-meth-
ylphenol (2 mol % with respect to the substrate). In addition,
the skeletal isomerization of cyclopropyl and cyclobutyl rings
did not take place under the present conditions.14 These facts
show that free radical intermediates are not involved in the
present oxidation. The competitive oxidation of alkylarenes
of xanthene, 9,10-dihydroanthracene, fluorene, triphenyl-
methane, and diphenylmethane was carried out. When the
relative rates were plotted against the heterolytic C-H bond
energy, the homolytic C-H bond energy, ionization poten-
tial, and pKa (Figure 1 and Figure S2, Supporting Informa-
tion), a fairly good correlation was observed between relative
rates versus the heterolytic C-H bond energy, suggesting
that the formation of carbocation-type transition state via the
hydride abstraction is involved in the present oxidation.
Here, we propose the possible mechanism for the Ru(OH)x/
Al2O3-catalyzed oxidation of alkylarenes in Scheme 1. This
catalytic oxidation can be divided into three steps: Initially,
the reaction of ruthenium hydroxide species I with an
alkylarene proceeds to form ruthenium hydride species II
and the intermediate alcohol (step 1). The hydride species
then reacts with molecular oxygen (step 2). The reoxidation
of the hydride species likely proceeds through the insertion
a Reaction conditions A: substrate (1 mmol), Ru(OH)x/Al2O3 (2 mol
%), PhCF3 (6 mL), 373 K, under 1 atm of molecular oxygen. Reaction
conditions B: substrate (1 mmol), Ru(OH)x/Al2O3 (5 mol %), o-dichlo-
robenzene (6 mL), 443 K, under 1 atm of molecular oxygen. Reaction
conditions C: Substrate (1 mmol), Ru(OH)x/Al2O3 (2 mol %), p-xylene (6
mL), 403 K, under 1 atm of molecular oxygen. Conversion and selectivity
were determined by GC with an internal standard. Carbon balance for each
reaction was greater than 95%. Values in parentheses are isoleted yields.
b These experiments used a recycled catalyst. The reaction conditions were
the same as those for the first runs with a fresh catalyst. The initial rates
for the recycled runs were the same as that for the first run with a fresh
catalyst. c 5H-Dibenzo[a,d]cyclohepten-5-one was formed (12% selectivity).
d Anthraquinone (5% selectivity) and anthrone (2% selectivity) were formed.
e 10-Methylanthrone was formed (8% selectivity). f 10-Phenylanthrone was
formed (18% selectivity).
oxygenation at the benzylic position proceeded selectively
to give the corresponding diaryl ketones in excellent yields
(entries 1 and 3). Larger scale oxidation of xanthene (20
mmol scale, Ru: 0.1 mol %) showed a turnover frequency
(TOF) of 278 h-1, a turnover number (TON) of 921, and a
yield of 92%. These values are the highest among those
reported for oxygenation of alkylarenes using 1 atm of
molecular oxygen so far: H5PV2Mo10O40 (TOF 3.2 h-1, TON
58 for xanthene),9a N-hydroxyphthalimide (TOF 0.5 h-1,
TON 10 for xanthene),8 Bu4NHSO4/NaOH (TOF 8.5 h-1,
TON 5 for xanthene),9b Ru-Co-Al-CO3 hydrotalcite (TOF
4.5 h-1, TON 9 for xanthene),9c Co Shiff base complex/2-
methylpropanal (TOF 0.5 h-1, TON 10 for fluorene).7
9,10-Dihydroanthracene derivatives were smoothly converted
(13) Under anaerobic conditions, the dehydration of 9-hydroxy-9,10-
dihydroanthracene to anthracene proceeded with the same rate as that in
the presence of molecular oxygen.
(14) (a) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2002, 41,
4538. (b) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2003, 42,
1480. (c) Yamaguchi, K.; Mizuno, N. Chem. Eur. J. 2003, 41, 4353.
Org. Lett., Vol. 6, No. 20, 2004
3579

Scheme 1. Possible Reaction Mechanism
Figure 1. Relative rates for the competitive oxidations of alky-
larenes, xanthene (X), 9,10-dihydroanthracene (DHA), triphenyl-
methane (T), diphenylmethane (DPM), and fluorene (F) as a
function of heterolytic bond energy. -∆Ghydride(R+) is the free
energy of R-H heterolytic bond disassociation: R-H f R+
+
H-.
rate-limiting step. A kinetic isotope effect (kH/kD) of 5.3 (
0.2 for the oxidation of fluorene and fluorene-d10 at 403 K
supports that the above C-H bond cleavage (step 1) is a
rate-limiting step (Supporting Information, Figure S6).6,9a
In conclusion, the present Ru(OH)x/Al2O3 catalyst can act
as an efficient heterogeneous catalyst for the oxidation of
alkylarene derivatives using molecular oxygen as the sole
oxidant. The oxidation of various alkylarenes can be per-
formed with high conversion and selectivity, giving the cor-
responding oxygenated or dehydrogenated products. Catalyst/
product separation is very easy, and the recovered catalyst
is reusable with retention of the high catalytic performance.
of molecular oxygen into the hydride species.14 In the case
of alkylarenes with one methylene group such as xanthene,
the oxidation of the intermediate alcohols proceeds to afford
the corresponding ketones by Ru(OH)x/Al2O3 (step 3). For
other substrates such as 9,10-dihydroanthracene, the dehy-
dration of the intermediate alcohols takes place, giving the
corresponding dehydrogenated products (step 3). It was
confirmed that the amounts of molecular oxygen consumed
was equivalent to that of the xanthen-9-one produced for
the oxidation of xanthene and that half that of anthracene
produced for the oxidation of 9,10-dihydroanthracene. The
formation of water for the oxidation of xanthene and 9,10-
dihydroanthracene with molecular oxygen was monitored,
and the respective amounts of water formed were the same
as those of the oxidation products of xanthen-9-one and
anthracene. These facts regarding the reaction stoichiometry
support the above oxidation mechanism by Ru(OH)x/Al2O3.
The initial rate (R0) of the xanthene oxidation was almost
independent of PO2 (>0.5 atm, Figure S4, Supporting
Information), while the dependence of R0 on the concentra-
tion of xanthene (0.017-0.30 M, Figure S5, Supporting
Information) was positive (0.5 th). These dependences show
that the reoxidation (step 2) proceeds smoothly and is not a
Acknowledgment. This work was supported by the Core
Research for Evolutional Science and Technology (CREST)
program of the Japan Science and Technology Corporation
(JST) and a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Science, Sports and Technol-
ogy of Japan.
Supporting Information Available: Experimental Sec-
tion and Figures S1-S6. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL0485363
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