Oxidation of secondary benzylic alcohols to ketones and benzylic oxygenation of alkylarenes with hydrogen peroxide in the presence of activated carbon

Article abstract of DOI:10.1055/s-0031-1290367

A variety of benzylic alcohols were oxidized to the corresponding carbonyl compounds selectively with 30% hydrogen peroxide (H in the presence of activated carbon. Alkylarenes such as fluorenes, xanthenes, and anthrone were also effectively oxygenated to the corresponding carbonyl compounds with 30% Has oxidant in the presence of activated carbon. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290367

LETTER
▌1683
letter
Oxidation of Secondary Benzylic Alcohols to Ketones and Benzylic Oxy-
genation of Alkylarenes with Hydrogen Peroxide in the Presence of Activated
Carbon
Oxidation of Secondary Benzylic Alcohols to Ketones
Shunsuke Nishida, Masahiko Hayashi*
Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe 657-8501, Japan
Fax +81(78)8035688; E-mail: mhayashi@kobe-u.ac.jp
Received: 23.03.2012; Accepted after revision: 19.04.2012
selenium dioxide, and periodic acid has been employed
Abstract: A variety of benzylic alcohols were oxidized to the cor-
traditionally. From the viewpoint of atom efficiency and
responding carbonyl compounds selectively with 30% hydrogen
environmental concerns, the development of methods us-
ing molecular oxygen or air has attracted much attention.
peroxide (H2O2) in the presence of activated carbon. Alkylarenes
such as fluorenes, xanthenes, and anthrone were also effectively ox-
ygenated to the corresponding carbonyl compounds with 30% H2O2 In recent years, benzylic oxidation of alkylaromatics to
as oxidant in the presence of activated carbon.
the corresponding carbonyl compounds with molecular
oxygen as oxidant using catalysts such as N-hy-
droxyphthalimide,13 Ru3+-substituted silicotungstate,14
Ru-Co-Al-CO3 hydrotalcite,15 CuCl–2,2′,3,3′,5,5′-hexa-
phenyl-(1,1′-biphenyl)-4,4′-dioxyl,16 Co(II)–Schiff base
complex17 has been reported. Methods using
photooxidation18 and controlled potential electrolysis19
have also been developed.
Key words: oxidation, benzylic alcohol, hydrogen peroxide, acti-
vated carbon, fluorene
Oxidation of alcohols into aldehydes and ketones is one of
the most fundamental reactions in organic synthesis.1 So
far, some stoichiometric oxidizing agents such as chromi-
um [Jones reagent,2 pyridinium chlorochromate (PCC),3
pyridinium dichromate (PDC)4] and manganese oxides
have been used for this purpose. However, these metal
salts are usually toxic and hazardous and they often cause
environmental problems. As the reagents without such
metal oxides, Swern oxidation (DMSO/oxalyl chloride),5
Dess–Martin oxidation,6 and TEMPO (2,2,6,6-tetrameth-
yl-1-piperidinyloxy) oxidation7 have been developed. On
the other hand, a catalytic process using molecular oxygen
or aqueous H2O2 as oxidizing agents by the aid of less tox-
ic metal complex is desirable from the viewpoints of en-
vironmental concerns. Markó et al. reported an efficient
catalytic system consisting of CuCl/phenanthro-
Herein, we report the oxidation of secondary benzylic al-
cohols to ketones and oxygenation of alkylarenes such as
fluorenes, xanthenes, and anthrone to afford the corre-
sponding oxygenated compounds with 30% H2O2 in the
presence of activated carbon (Scheme 1).
At first, we selected 9-fluorenol as a substrate. As we ex-
pected, 9-fluorenone was obtained in 77% yield (100
weight% of activated carbon, m-xylene, 95 °C, 18 h) when
ten equivalents of 30% H2O2 were used. Less (4 equiv)
and more amounts (15 equiv) of 30% H2O2 caused the de-
crease of yield (68% and 35%, respectively).
Table 1 Oxidation of 9-Fluorenol
line/K2CO3/DBADH2
[1,2-bis(tert-butoxycarbonyl)-
hydrazine]8 and TPAP(tetrapropylammonium perruthe-
nate)/MS 4 Ǻ9 using oxygen or air as oxidant. Noyori and
co-workers developed organic solvent- and halide-free
oxidation of alcohol with aqueous H2O2 using Na2WO4
and a phase-transfer catalyst (PTC) system.10 We also re-
ported the oxidation of secondary benzyl and allylic alco-
hol leading to the formation of the corresponding ketones
by Pd/C–ethylene system11 and activated carbon–molecu-
lar oxygen system.12
H2O2 (x equiv)
activated carbon (100 wt%)
xylene, 95 °C, 18 h
OH
O
X (equiv)
Yield (%)a
1
2
3
4
10
15
68
77
35
Furthermore, direct oxygenation of alkylarenes to the cor-
responding carbonyl compounds is a highly important re-
action because an oxygen atom can be introduced into
organic substrates. For these transformations, also a stoi-
chiometric amount of an oxidant such as manganese diox-
ide, chromic acid, potassium dichromate, silver oxide,
a Isolated yield after silica gel column chromatography.
Then, we examined the oxidation of a variety of benzylic
alcohols. Some of the obtained examples are summarized
in Table 1. As shown in Table 1, various benzylic alcohols
were converted into the corresponding ketones.
SYNLETT 2012, 23, 1683–1685
Advanced online publication: 13.06.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0031-1290367; Art ID: ST-2012-U0271-L
© Georg Thieme Verlag Stuttgart · New York

1684
S. Nishida, M. Hayashi
LETTER
Thus, we have disclosed here that the activated carbon–
30% H2O2 system works efficiently for the oxidation of a
variety of benzylic alcohols without any metals. During
the course of these studies, we found that a direct intro-
duction of oxygen at the benzylic position took place.
That is, treatment of fluorene with 100 weight% of acti-
vated carbon in m-xylene at 95 °C for 18 hours in the pres-
ence of 30% H2O2 afforded 9-fluorenone in 71% yield.
H2O2 (30%)
R1
R2
OH
R1
R2
activated carbon (100 wt%)
xylene, 95 °C, 18 h
O
Ph
Me
N
Ph
N
N
O
O
O
64%
74%
67%
The results for the oxygenation of 2-substituted fluorenes
and other alkylarenes with 30% H2O2 in the presence of
activated carbon are summarized in Scheme 2. A variety
of fluorene derivatives and alkylarenes such as xanthene,
thioxanthene, and anthrone were employed to afford the
corresponding carbonyl compounds in good to high yield
(43–71% yield). It is noteworthy that the sulfur atom of
thioxanthene was not oxygenated.
O
Ph
Ph
O
O
77%
91%
(from benzoin)
Scheme 1 Oxidation of various alcohols to the corresponding car-
bonyl compounds
30% H2O2 was supposed to decompose to O2 and H2O at
95 °C in the presence of activated carbon. We think the ac-
tual oxidizing source will be O2. Furthermore, the addition
of hydroquinone to the reaction mixture retarded the reac-
tion remarkably, so we proposed the mechanism involv-
ing radical species as shown in Scheme 3. Micropores in
activated carbon should be believed to play an essential
role in this oxidation.20
H2O2 (30%)
R1
O
R2
activated carbon
R1
R2
xylene, 95 °C, 18 h
O
NHAc
Finally, we found that the urea–H2O2 complex is also
available instead of 30% H2O2, that is, the oxidation of 9-
fluorenol proceeded in the presence of four equivalents of
urea–H2O2 and activated carbon to give 9-fluorenone in
90% yield (Scheme 4).21
O
71%
O
51%
O
43%
S
O
In conclusion, we have revealed that a variety of benzylic
alcohols were oxidized to the corresponding carbonyl
compounds selectively with 30% hydrogen peroxide in
the presence of activated carbon. Alkylarenes such as
fluorenes, xanthenes, and anthrone were also effectively
oxygenated to the corresponding carbonyl compounds
O
49%
O
68%
Scheme 2 Carbonylation using an activated carbon–H2O2 system
O2
•
O
activated carbon
•
O2
•
O
O
H
H2O
O
O
H
OH
Scheme 3
Synlett 2012, 23, 1683–1685
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidation of Secondary Benzylic Alcohols to Ketones
1685
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Scheme 4
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Acknowledgment
We acknowledge Prof. Ryosuke Matsubara of Kobe University for
helpful discussion. This work was supported by a Grant-in-Aid for
Scientific Research on Innovative Areas, MEXT, Japan ‘Molecular
Activation Directed toward Straightforward Synthesis’ and No.
B23350043 from the Ministry of Education, Culture, Sports, Sci-
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
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(21) The detail of urea–H2O2-activated carbon system will be
published in a separate paper.
(22) General Experimental Procedure
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