Efficient aerobic oxidation of alcohols to carbonyl compounds with NHPI/CAN catalytic system

Article abstract of DOI:10.1081/SCC-120038507

Aerobic oxidation of various secondary alcohols into their corresponding carbonyl compounds has been accomplished by using N-hydroxy phthalimide (NHPI)/ceric ammonium nitrate (CAN). Primary alcohol and allylic alcohols were transformed in relatively moderate yield.

Full text of DOI:10.1081/SCC-120038507

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Efficient Aerobic Oxidation of Alcohols to Carbonyl
Compounds with NHPI/CAN Catalytic System
a
a
Sung Soo Kim & Gurusamy Rajagopal
a
Department of Chemistry and Center for Chemical Dynamics , Inha University ,
Incheon, 402‐751, South Korea
Published online: 17 Aug 2006.
To cite this article: Sung Soo Kim & Gurusamy Rajagopal (2004) Efficient Aerobic Oxidation of Alcohols to Carbonyl
Compounds with NHPI/CAN Catalytic System, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:12, 2237-2243, DOI: 10.1081/SCC-120038507
To link to this article: http://dx.doi.org/10.1081/SCC-120038507
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 12, pp. 2237–2243, 2004
Efficient Aerobic Oxidation of Alcohols to
Carbonyl Compounds with NHPI/CAN
Catalytic System
#
*
Sung Soo Kim and Gurusamy Rajagopal
Department of Chemistry and Center for Chemical Dynamics,
Inha University, Incheon, South Korea
ABSTRACT
Aerobic oxidation of various secondary alcohols into their corresponding
carbonyl compounds has been accomplished by using N-hydroxy phthal-
imide (NHPI)/ceric ammonium nitrate (CAN). Primary alcohol and
allylic alcohols were transformed in relatively moderate yield.
Key Words: Carbonyl compounds; Catalytic system; Aerobic oxidation;
Secondary alcohols.
*
Correspondence: Sung Soo Kim, Department of Chemistry and Center for Chemical
Dynamics, Inha University, Incheon 402-751, South Korea; Fax: þ82-32-8675604;
E-mail: sungsoo@inha.ac.kr.
#
Dr. G. Rajagopal is a Brain Pool Scientist from the Department of Chemistry, Crescent
Engineering College, Chennai 600 048, India and he was assisted by a grant from the
Korean Federation of Science and Technology Societies and the Korea Science and
Engineering Foundation.
2
237
DOI: 10.1081/SCC-120038507
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Kim and Rajagopal
INTRODUCTION
The development of efficient catalytic system for selective organic trans-
formation is currently one of the challenging tasks in synthetic organic chem-
istry. The oxidation of alcohol into their corresponding carbonyl compounds is
[1]
one of the most important transformations in organic synthesis. N-Hydroxy
phthalimide (NHPI) has first been used as an efficient electron carrier for the
[
2]
electrochemical oxidation of alcohols.
efficiently catalyzes the aerobic oxidation of various organic substrates to
Then Ishii et al. found that NHPI
[3]
oxygen containing compounds, under non-electrochemical conditions. An
efficient catalytic method for the low temperature oxygenation of organic
compound with dioxygen was developed by using NHPI as a catalyst and a
metal salt as co-catalyst. With this system, organic compounds containing
[4]
[5]
sufficiently reactive C–H bonds, e.g., (cyclic)alkanes, sulfoxides, alkyl
have
[
benzenes, and aromatic compounds containing benzylic functions,
6]
[7–9]
been oxidized at moderate temperature up to high conversion. A methodology
for the aerobic oxidation of organic compounds has been established using a
combined catalytic system consisting of NHPI/quaternary ammonium
[
10]
[11]
bromide.
Hydroxylations of polycyclic alkanes
with molecular oxygen
in the presence of NHPI combined with cobalt salts under mild conditions
have been reported. A variety of alkenes were epoxidized in a regio- and stereo-
selective manner with oxygen in the presence of benzhydrol catalyzed by NHPI
[
12]
and hexafluroacetone.
been performed by using a new series of substituted NHPI
Ceric ammonium nitrate (CAN) itself is a well-known oxidizing agent that
Electro catalytic oxidation of several alcohols have
[13]
as catalysts.
[
14–16]
oxidizes various organic substrates.
[
Aerobic oxidation of alkyl malonates
into ketomalonates employs catalytic amount of CAN. In the continuing
17]
[18–21]
interest of our alcohol oxidation studies,
the aerobic oxidation of benzylic alcohols using NHPI/CAN system.
we would like to herein report
RESULTS AND DISCUSSION
sec-Phenylethyl alcohol was chosen for several control experiments to
study the role of the each reagent utilized in the reaction (Table 1). NHPI
and CAN are the most important species for the oxidation process. Without
these reagents, there is very little oxidation reaction (entries 1 and 2) taking
place. Without oxygen bubbling, the oxidation gives only 51% of aceto-
phenone (entry 3). Elevated temperature is also needed for efficient oxidation
(
entry 4). An efficient oxidative condition is described with entry 6.
Investigations of the scope of the substrates were conducted under the
optimized condition as mentioned above and the results were given in

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Aerobic Oxidation of Secondary Alcohols
2239
Table 1. Oxidation of sec-phenethyl alcohol under various condition by using
a
NHPI/CAN system in CH CN.
3
CAN
(mol%)
NHPI
(mol%)
Time
(hr)
Yield
(%)
b
Entry
O
2
1
2
3
4
5
6
—
20
20
20
10
20
10
—
10
10
10
10
O
2
5
Trace
Trace
51
O2
—
1.15
1.15
4
O
2
48
68
O2
O2
1.15
1.15
91
a
3
All the reactions except for entry 4 were carried out with reflux temperature of CH CN
(
b
b.p. 828C). Entry 4 was reacted at RT.
O was bubbled in all reactions except for entry 3. Entry 3 was reacted on the air
2
2
without O bubbling.
Table 2. Unsubstituted and substituted phenylethanols (entries 1–6) were
efficiently oxidized to corresponding ketones with excellent yield (.90%).
The change of methyl group of 1-phenylethanol into larger groups prolongs
the reaction time (entries 7–10). 1-Indanol and 1,2,3,4-tetrahydro-1-naphthol
were converted into their corresponding ketones with good yields (entries 11
and 12). Cyclopropyl benzyl alcohol has undergone smooth oxidation with
moderate yield (entry 13). Benzyl alcohol, cinnamyl alcohol and (2) carveol
produced poor yield of ketones (49–61%).
[
3,20]
On the basis of previous oxidation studies,
has been proposed as indicated in Sch. 1. Dioxygen is reduced to H O by
the following mechanism
2
2
3
þ
4þ
the oxidation of Ce to Ce . NHPI can be converted into phthalimide-
N-oxyl (PINO) radical. PINO then oxidizes the alcohol to corresponding
ketone.
In conclusion, present catalytic system is useful for the oxidation of
secondary benzylic alcohols to ketones. Primary and allylic alcohol reveal
poor oxidation tendency.
EXPERIMENTAL
General Procedure for the Oxidation of Alcohols Catalyzed by
NHPI/CAN System
Alcohol (1 mmol), CAN (20 mol%), and NHPI (10 mol%) were dis-
solved in 3 mL of CH CN in a three necked round-bottom flask equipped
3

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Kim and Rajagopal
3
Table 2. Oxidation of alcohols by NHPI/CAN system in CH CN.
a,b
Time
(hr)
Yield
(%)
Entry
1
Substrate
1
.2
91
2
3
4
1.3
1.5
1.3
95
96
97
5
1
93
6
7
1.3
1.3
90
95
8
2.3
93
(
continued)

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Aerobic Oxidation of Secondary Alcohols
Table 2. Continued.
2241
a,b
Time
(hr)
Yield
(%)
Entry
9
Substrate
2
.3
92
1
1
0
1
2.5
96
86
45 min
1
2
3
1.3
2.3
88
83
1
a
Isolated yield.
1
All the H NMR spectra of ketones and aldehydes exactly match with those tabulated
b
1
3
1
in the Aldrich library of C and H FT NMR spectra edited by Charles J. Pouchert,
Jacqlynn Behnke.
Scheme 1.

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Kim and Rajagopal
with a condenser and magnetic bar. This mixture was heated to reflux with an
oil bath under continuous stream of oxygen. The progress of the reaction was
monitored by using TLC. After completion of the reaction, excess solvent
was evaporated under reduced pressure and the product was purified by
flash column chromatography on silica gel by using ethyl acetate/hexane
1
mixture as eluent. The products thus separated were identified by H NMR
spectroscopy.
ACKNOWLEDGMENT
The authors warmly thank the Korea Research Foundation for the finan-
cial support (KRF-2002-015-CP0203).
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Received in Japan December 16, 2003

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