TEMPO-catalyzed oxidation of benzylic alcohols to aldehydes with the H 2O2/HBr/ionic liquid [bmim]PF6 system

Article abstract of DOI:10.1016/j.tetlet.2005.03.078

A selective oxidation of benzylic alcohols to the corresponding aldehydes in room temperature ionic liquid was achieved by using TEMPO/HBr/H ₂O₂ system, and both ether-insoluble acetamido-TEMPO and ionic liquid [bmim]PF₆ can be successfully recovered and reused for the oxidation of the same (different) substrate.

Full text of DOI:10.1016/j.tetlet.2005.03.078

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3323–3326
TEMPO-catalyzed oxidation of benzylic alcohols to aldehydes
with the H O /HBr/ionic liquid [bmim]PF system
2
2
6
Nan Jiang and Arthur J. Ragauskas*
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, United States
Received 17 February 2005; revised 11 March 2005; accepted 15 March 2005
Available online 2 April 2005
Abstract—A selective oxidation of benzylic alcohols to the corresponding aldehydes in room temperature ionic liquid was achieved
by using TEMPO/HBr/H
recovered and reused for the oxidation of the same (different) substrate.
2005 Elsevier Ltd. All rights reserved.
2 2 6
O system, and both ether-insoluble acetamido-TEMPO and ionic liquid [bmim]PF can be successfully
ꢀ
The oxidation of alcohols into the corresponding alde-
hydes or ketones is a fundamentalreaction in both
Furthermore, a proper choice of cation and anion pro-
vides a fine-tuning of their miscibility with water and
common organic solvents. Thus, ionic liquids have been
used as solvents in a wide range of organic reactions,
1
laboratory and industrial synthetic chemistry. Usually,
environmentally hazardous oxidizing agents (i.e.,
KMnO , MnO , CrO , SeO , etc.) in stoichiometric
1
0
11
12
such as Diels–Alder, Friedel–Crafts, Heck, and
13
4
2
3
2
2
14
amount are necessary to perform this transformation.
Suzuki coupling reactions, hydroformylation, hydro-
1
genation, olefin dimerization, and oligomerization.
5
16
17
With the increasingly environmental consciousness of
academia and industry research, the search for more
effective catalytic oxidation process that use clean, inex-
pensive terminal oxidants, such as molecular oxygen or
aqueous hydrogen peroxide, remains an important chal-
However, only recently have the potential benefits of
oxidation in ionic liquids been examined. Reported
reactions include Ni(acac) -catalyzed aerobic oxidation
2
1
8
19
of aromatic aldehydes, ruthenium-catalyzed, or cop-
20
3
lenge. Recently, many examples of homogeneous sys-
6
tems making use of palladium, ruthenium, copper,
per-TEMPO-catalyzed aerobic oxidation of alcohols,
21
4
5
palladium-catalyzed oxidation of styrene and benzyl
22
7
or cobalt compounds as catalysts for aerobic alcohol
oxidation with molecular oxygen as terminal oxidant
have been reported. However, most of these catalytic
systems are performed in aromatic or halogenated
hydrocarbon solvents with low catalytic activity.
alcohol, osmium-catalyzed dihydroxylation of alk-
2
enes, and rhenium-catalyzed Baeyer-villiger reaction.
3
24
Our interest in exploring the potential of aqueous
hydrogen peroxide as green oxidant prompted us to
investigate alcohol oxidation in ionic liquids. Inspired
by the results of TEMPO-Br /I system for alcohol oxi-
On the other hand, the reduction/replacement of volatile
organic solvents from the reaction media is of high prio-
2
2
2
5
dation and H O –HBr system for benzylic bromina-
2
2
8
26
rity in the Green Chemistry focus area. Ionic liquids,
composed entirely of ions with melting point below
tion, we now report a highly selective oxidation of
benzylic alcohols to aldehydes using a three-component
catalytic system consisting of H O , HBr, and TEMPO
9
1
00 ꢁC, are now emerging as promising and attractive
2
2
alternatives due to their unique properties including
low volatility, high polarity, stability over a wide tem-
perature range, and capacity to dissolve a variety
of organic, inorganic, and organometallic compounds.
with an ionic liquid as the solvent.
3
mol% TEMPO, 6 mol% HBr
eq. H O , [bmim]PF , r.t.
CH OH
CHO
2
3
Keywords: TEMPO; Alcohol oxidation; Benzylic alcohols; Ionic
2
2
6
6
liquids; [bmim]PF .
38%
*
Corresponding author. Tel.: +1 404 894 9701; fax: +1 404 894
778; e-mail: arthur.ragauskas@chemistry.gatech.edu
4
Scheme 1.
0
040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.078

3324
N. Jiang, A. J. Ragauskas / Tetrahedron Letters 46 (2005) 3323–3326
Table 1. Optimization of the reaction conditions for oxidizing benzyl
a
alcohol to benzaldehyde
study was carried out using benzyla cl oholas substrate
and 3 equiv of aqueous hydrogen peroxide (50%) at
ambient temperature in the presence of 6 mol% HBr
and 3 mol% TEMPO ( Scheme 1). The oxidation pro-
ceeded smoothly and 38% isolated yield of benzaldehyde
was obtained with 42% conversion and 98% selectivity
b
c
Entry
1
H
2
2
O /PhCHO ratio
Convn./Sel. (%)
Yield (%)
3
3
3
3
2
2
2
2
2
2
98/99
36/97
38/99
6/99
90
31
36
—
89
92
90
92
88
91
d
2
e
3
f
1
4
(2% benzoic acid detected by H NMR) after 2 h stir-
5
98/97
98/98
98/98
99/96
99/97
98/96
ring. Increasing the reaction temperature to 40 ꢁC,
98% conversion and 90% isolated yield was obtained
under the identicalcondition.
g
6
h
7
h
8
h
9
Further efforts were then focused on optimizing the
reaction condition. The conversion, selectivity, and yield
of the oxidation under different conditions are summa-
rized in Table 1. For the comparison, the common
organic solvents, ethyl acetate, and chloroform, were
also tested for the oxidation of benzyl alcohol under
the same condition, and reasonable conversions and
yields were obtained (Table 1, entries 2 and 3). At the
same time, iodine (3 mol%) was used to rep la ce aqueous
HBr as co-catalyst for the oxidation, and only 6%
h
0
1
a
2
mmol benzyl alcohol, 50% aqueous H
mol% HBr, 1 mL [bmim]PF
, 40 ꢁC, 2 h.
Conversion and selectivity were determined by H NMR of the crude
2 2
O , 3 mol% TEMPO,
6
6
b
1
product mixture.
Isolated yield by flash chromatography.
c
d
e
f
1
1
mL EtOAc as solvent.
mL CHCI as solvent.
mol% I was used to replace HBr.
3
3
2
g
h
Acetamido-TEMPO was used as catalyst.
Recycling experiment for both [bmim]PF
TEMPO.
1
6
and catalyst acetamido-
conversion was detected by H NMR of the crude
reaction mixture. Recognizing that H O was partially
2
2
decomposed during the reaction, we sought to reduce
the amount of hydrogen peroxide by adding it in two
portions. Indeed, 98% conversion, 97% selectivity, and
The room temperature ionic liquid [bmim]PF was cho-
6
sen, due to its immiscibility with water, and the initial
a
6
Table 2. Oxidation of alcohols to aldehydes in [bmim]PF
b
Entry
Benzylic alcohols
Condition
2 equiv H
Products
Yields (%)
92
1
2
O
O
O
O
O
O
O
2
2
2
2
2
2
2
, 2 h
, 3 h
, 3 h
, 2 h
, 4 h
, 4 h
, 4 h
CH OH
CHO
2
2
equiv H
2
2
2
2
2
2
83
81
87
93
2
3
CH OH
CHO
CHO
2
CH OH
2
2 equiv H
2 equiv H
3 equiv H
5 equiv H
3 equiv H
4
5
6
7
CH OH
CHO
2
CH OH
CHO
2
Cl
Cl
CH OH
CHO
2
c
72
O N
O N
2
2
Br
CH OH
Br
CHO
CHO
91
2
8
9
NC
CH OH
4 equiv H
2
2
O
2
, 4 h
, 2 h
NC
83
—
2
MeO
CH OH
2 equiv H
O
2
MeO
CHO
2
a
b
c
The reactions were carried out in 2 mmolsca el at 40 ꢁC.
Isolated yield by flash chromatography.
The reaction was carried out at 50 ꢁC.

N. Jiang, A. J. Ragauskas / Tetrahedron Letters 46 (2005) 3323–3326
3325
89% isolated yield was obtained even by using 2 equiv of
hydrogen peroxide (Table 1, entry 5).
In conclusion, an efficient oxidation of benzylic alcohols
to aldehydes by using TEMPO/HBr/H O system has
been achieved in ionic liquid [bmim]PF . The electron-
2
2
6
Furthermore, TEMPO is a rather expensive chemical
agent, and efficient recycling of TEMPO is very desir-
able. Several groups have addressed this problem by
designing and synthesizing heterogeneous variant of
TEMPO. In our present reaction condition, TEMPO
cannot be reused in ionic liquid after ether extraction,
due to its good solubility in ether. Surprisingly, we
found that the commercial available acetamido-TEMPO
deficient and electron-neutral benzylic alcohols were
oxidized in good to excellent yields, whereas the elec-
tron-rich benzylic alcohol failed to afford the target
product due to side-reaction. The process is simple
and mild. Most importantly, the ether-insoluble acetam-
ido-TEMPO can be recycled and reused in ionic liquid
[bmim]PF6 for the oxidation of the same (different)
substrate.
2
7
has very good solubility in [bmim]PF , but is insoluble
6
in ether, which encouraged us to recycle acetamido-
TEMPO in [bmim]PF6 for this oxidation. To our
delight, acetamido-TEMPO afforded the comparable
conversion, selectivity, and yield (Table 1, entry 6). A
second run was then performed by adding fresh benzyl
alcohol, hydrogen peroxide, and 6 mol % aqueous HBr
to the ionic liquid under the same experimental condi-
tions. It was noteworthy that the benzaldehyde was
obtained in the similar conversion, selectivity, and yield
without addition of acetamido-TEMPO, indicating that
both the ionic liquid and the catalyst were recoverable
and reusable (Table 1, entry 7). This catalytic system
was stable and efficient for three more recycling without
significant loss of catalytic capability (Table 1, entries 8–
Acknowledgments
This project was supported by the NationalResearch
Initiative of the USDA Cooperative State Research,
Education and Extension Service, grant number 2003-
3
5504-13620.
References and notes
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1
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2
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6
1
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(
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% HBr
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[
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1
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2
2
CHO
Scheme 2.

3326
N. Jiang, A. J. Ragauskas / Tetrahedron Letters 46 (2005) 3323–3326
1
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(13.0 mg, 3 mol%) in 1 mL room temperature ionic li quid
[bmim]PF6 was added 48% aqueous hydrobromic acid
(20 mg, 6 mol%). The reaction mixture was capped and
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4
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