Benzylic oxygenation of alkylarenes with molecular oxygen in the presence of activated carbon

Article abstract of DOI:10.1016/j.tetlet.2004.05.030

A variety of alkylarenes such as fluorenes, xanthenes, and anthrone were effectively oxygenated to the corresponding carbonyl compounds with molecular oxygen as oxidant in the presence of activated carbon.

Full text of DOI:10.1016/j.tetlet.2004.05.030

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5457–5459
Benzylic oxygenation of alkylarenes with molecular oxygen
in the presence of activated carbon
Hirotoshi Kawabata and Masahiko Hayashi*
Department of Chemistry, Faculty of Science, Kobe University, Nada, Kobe 657-8501, Japan
Received 12 April 2004; revised 3 May 2004; accepted 10 May 2004
Abstract—A variety of alkylarenes such as fluorenes, xanthenes, and anthrone were effectively oxygenated to the corresponding
carbonyl compounds with molecular oxygen as oxidant in the presence of activated carbon.
Ó 2004 Elsevier Ltd. All rights reserved.
Oxidation is one of the most fundamental transforma-
1
tions in organic chemistry. Direct oxygenation of al-
oxygen promoted by activated carbon, which led to the
synthesis of the corresponding pyridines, pyrazoles, and
anthracenes. We also disclosed that 2-arylbenzoxazoles
were directly synthesized from substituted 2-aminophe-
nols and aldehydes under oxygen atmosphere in the
presence of activated carbon in xylene. As an extension
of the above novel oxidation system, we examined the
oxidation of alcohols using an activated carbon–oxygen
system. At first, we selected 9-fluorenol as a substrate.
As we expected, 9-fluorenone was obtained in 83% yield
(100 wt % of Shirasagi KL, m-xylene, 120 °C, 22 h)
(Eq. 1).
kylarenes to the corresponding carbonyl compounds is a
highly important reaction because an oxygen atom can
be introduced into organic substrates. For these trans-
formations, a stoichiometric amount of an oxidant such
as manganese dioxide, chromic acid, potassium dichro-
mate, silver oxide, selenium dioxide, and periodic acid
11
1
has been employed traditionally. From the viewpoint of
atom efficiency and environmental concerns, however,
the development of methods using molecular oxygen or
air has attracted much attention. In recent years, benz-
ylic oxidation of alkylaromatics to the corresponding
carbonyl compounds with molecular oxygen as oxidant
O
2
Shirasagi KL
m-xylene
120 °C, 22 h
2
3þ
using catalysts such as N-hydroxyphthalimide, Ru -
3
ð1Þ
substituted silicotungstate, Ru–Co–Al–CO hydrotal-
3
OH
O
4
0 0 0 0
cite,
0
CuCl–2,2 ,3,3 ,5,5 -hexaphenyl-(1,1 -biphenyl)-
5
6
4
ported. Methods using photooxidation and controlled
,4 -dioxyl, Co(II)–Schiff base complex has been re-
7
During the course of these studies, we found direct
introduction of oxygen at the benzylic position took
place. That is, treatment of fluorene with 100 wt % of
activated carbon (Shirasagi KL) in m-xylene at 120 °C
for 24 h under oxygen atmosphere afforded 9-fluorenone
8
potential electrolysis have also been developed. Herein,
we report a highly efficient oxygenation of alkylarenes
such as fluorenes, xanthenes, and anthrone to afford the
corresponding oxygenated compounds in the presence
of activated carbon (Shirasagi KL, Japan Enviro-
12
â
in 83% yield (Table 1, entry 1). Darco KB and
â
Darco KB-B were also effective promoters to give the
oxygenated product in 72% and 67% yield, respectively
â
Chemicals, Ltd, or Darco KB, Aldrich, Inc.) under
oxygen atmosphere.
â
(entries 2 and 3). It was found that Darco G-60, which
had smaller surface area (600 m /g) compared with
2
We recently reported oxidative aromatization of Han-
9
â
2
â
2
Darco KB (1500 m /g) and Darco KB-B (1500 m /g)
exhibited lower reactivity. Similar results were also
found in our previously reported oxidative aromatiza-
tzsch 1,4-dihydropyridines, 1,3,5-trisubstituted pyraz-
9
olines, and 9,10-dihydroanthracenes using molecular
10
10;11
â
tions.
KB treated with 2 M HCl or HNO
When pretreated activated carbons, Darco
3
in advance to
remove contained metals in the activated carbon, were
Keywords: Oxygenation; Activated carbon.
*
Corresponding author. Tel.: +81-78-803-5687; fax: +81-78-803-5688;
e-mail: mhayashi@kobe-u.ac.jp
employed under the same conditions (120 °C, 24 h),
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.030

5458
H. Kawabata, M. Hayashi / Tetrahedron Letters 45 (2004) 5457–5459
a
Table 1. Oxygenation of fluorene under oxygen atmosphere
In Table 2, the results of the application of oxygenation
of 2-substituted fluorenes and other alkylarenes with
molecular oxygen in the presence of activated carbon
O
2
activated carbon
â
m-xylene
20 °C, 24 h
(Shirasagi KL or Darco KB) are summarized. A vari-
ety of fluorene derivatives possessing a substituent such
as NO , CHO, and NHCOCH at the 2-position was
1
O
b
2
3
Entry
Activated carbon
Shirasagi KL
Yield (%)
employed to afford the corresponding fluorenones in
high yield (69–77% yield) (entries 1–5). Shirasagi KL
1
2
83 (11)
72 (24)
67 (29)
51 (29)
7 (83)
â
d
Darco KB
â
â
and Darco KB showed similar performance. It should
c
d
3
c
Darco KB-B
â
d
be noted that the aldehyde function was not oxidized to
carboxylic acid under these conditions. For other
alkylarenes such as xanthene, thioxanthene, and an-
throne were employed (entries 6–9). The activated car-
bon–oxygen system also exhibited high performance in
these reactions. That is, these alkylaromatics were
treated with 100 wt % of activated carbon (Shirasagi KL
4
Darco G-60
None
5
a
All reactions were carried out using 100 wt % of activated carbon.
Isolated yield after silica gel column chromatography. Each value in
parentheses indicates the yield of recovered fluorene.
Reaction was carried out for 26 h.
b
c
d
2
Surface area: Darco KB (1500 m /g) ¼ Darco KB-B > Darco G-60
â
2
or Darco KB) at 120 °C in m-xylene for 9–50 h to give
the corresponding oxygenated products in high yield
(
600 m /g) (data from Aldrich, Inc.).
(84–94% yield) (entries 6–10). It is noteworthy that the
major differences in the yield of fluorenone were not
observed (69–72% yield). Thus, it would be considered
that the surface area of the activated carbon might more
strongly affect the reactivity than the metals in the
activated carbon. In the case of the reaction without
activated carbon (entry 5), the yield of fluorenone was
reduced to 7%. It is noteworthy that the presence of
activated carbon is essential for oxygenation under
oxygen atmosphere.
sulfur atom of thioxanthene was not oxygenated (entries
9 and 10). Diphenylmethane was not converted
smoothly to afford benzophenone in low yield (entries
11 and 12).
The reaction would proceed via a benzylic radical gen-
erated by the action of molecular oxygen to induce
cleavage of the benzylic C–H bond. After subsequent
oxygenation of the benzylic radical with oxygen and
a
Table 2. Oxygenation of fluorene derivatives and other alkylarenes under oxygen atmosphere in the presence of activated carbon
b
Entry
Substrate
Activated carbon
Time/h
Product
Yield (%)
1
2
Shirasagi KL
â
32
32
76
77
Darco KB
CHO
NO2
CHO
O
3
4
Shirasagi KL
â
95
79
77
69
Darco KB
NO
2
O
5
6
Shirasagi KL
82
10
71
NHAc
NHAc
O
O
O
c
Shirasagi KL
Shirasagi KL
84
O
O
O
S
7
8
50
50
94
94
â
Darco KB
O
S
9
Shirasagi KL
â
9
9
88
88
10
Darco KB
O
O
d
1
1
2
Shirasagi KL
â
50
48
26 (77)
13 (84)
d
1
Darco KB
a
b
c
All reactions were carried out using 100 wt % of activated carbon in m-xylene under an oxygen atmosphere.
Isolated yield after recrystallization.
1
Yield was determined by H NMR analysis using anthracene as an internal standard.
Isolated yield after silica gel column chromatography. Each value in the parentheses indicates the yield of recovered starting material.
d

H. Kawabata, M. Hayashi / Tetrahedron Letters 45 (2004) 5457–5459
5459
abstraction of a hydrogen atom from the starting
References and notes
material, peroxides would be produced. The intermedi-
ate peroxide might be decomposed to hydroxyl and
benzyloxy radicals. The latter radicals would be trans-
formed to the corresponding benzylic alcohols. Then,
oxidation of the alcohols with oxygen would take place
to furnish the corresponding carbonyl compounds.
Actually, 9-fluorenol was readily converted into 9-flu-
orenone by using the activated carbon–oxygen system as
mentioned in Eq. 1. The fact that the addition of
hydroquinone retarded the reaction would support the
reaction proceeds via radical intermediates.
1. Hudlicky, M. Oxidations in Organic Chemistry. In ACS
Monograph series; American Chemical Society: Washing-
ton, DC, 1990.
2
. (a) Fukuda, O.; Sakaguchi, S.; Ishii, Y. Adv. Synth. Catal.
001, 343, 809; (b) Tashiro, Y.; Iwahama, T.; Sakaguchi,
2
S.; Ishii, Y. Adv. Synth. Catal. 2001, 343, 220; (c)
Shibamoto, A.; Sakaguchi, S.; Ishii, Y. Org. Process Res.
Dev. 2000, 4, 505; (d) Matsunaka, K.; Iwahama, T.;
Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1999, 40, 2165;
(e) Ishii, Y.; Nakayama, K.; Takeno, M.; Sakaguchi, S.;
Iwahama, T.; Nishiyama, Y. J. Org. Chem. 1995, 60, 3934.
. Yamaguchi, K.; Mizuno, N. New J. Chem. 2002, 26, 972.
. Matsushita, T.; Ebitani, K.; Kaneda, K. Chem. Commun.
3
4
In conclusion, fluorene derivatives and related com-
pounds were found to be oxidized at the benzylic posi-
tion to the corresponding carbonyl compounds using
molecular oxygen promoted by activated carbon. Pre-
activation of activated carbon is not necessary and the
activated carbon is reusable after the reaction. The
present method is advantageous from the viewpoint of
low costs, environmental friendliness, and operational
simplicity. Further investigations on the detailed reac-
tion mechanism including the role of activated carbon,
are currently under way.
1
999, 265.
. Barbiero, G.; Kim, W.-G.; Hay, A. S. Tetrahedron Lett.
994, 35, 5833.
. (a) Maikap, G. C.; Guhathakurta, D.; Iqbal, J. Synlett
995, 189; (b) Punniyamurthy, T.; Iqbal, J. Tetrahedron
5
6
1
1
Lett. 1994, 35, 4003.
. Santamaria, J.; Jroundi, R. Tetrahedron Lett. 1991, 32,
7
4291.
8. Singh, K. N.; Singh, S. Bull. Electrochem. 2000, 16, 385.
9. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett.
2
002, 4, 3955.
0. Nakamichi, N.; Kawabata, H.; Hayashi, M. J. Org. Chem.
003, 68, 8272.
1
1
1
2
1. Kawashita, Y.; Nakamichi, N.; Kawabata, H.; Hayashi,
M. Org. Lett. 2003, 5, 3713.
Acknowledgements
2. Typical procedure for oxygenation using activated carbon
under oxygen atmosphere is as follows: A mixture of
fluorene (524 mg, 3.15 mmol) and Shirasagi KL (524 mg)
in m-xylene (5 mL) was placed in a reaction tube under an
oxygen atmosphere and stirred at 120 °C for 24 h. The
reaction mixture was filtered. The filtrate was then
concentrated and the obtained residue was isolated by
silica gel column chromatography to afford 9-fluorenone
(471 mg, 83% yield) as a yellow solid.
We gratefully acknowledge financial support from a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Culture, Sports, Science, and Technology,
Japan. We appreciate Japan EnviroChemicals, Ltd for a
generous gift of Shirasagi KL. H.K. is grateful to the
Japan Society for the promotion of Science (JSPS)
Research Fellowships for Young Scientists.