An Efficient Aerobic Oxidation of Alcohols to Aldehydes and Ketones with TEMPO/Ceric Ammonium Nitrate as Catalysts

Article abstract of DOI:10.1055/s-2003-41065

Secondary benzylic alcohols with an alkyl chain are oxidized faster than simple benzyl alcohols. However the reaction time is prolonged, when the alkyl chain is replaced by a bulky phenyl ring such as benzhydrol and 9-hydroxyfluorene. All the benzyl and benzylic alcohols give yields >90%. Allylic alcohols without steric hindrance react faster to give excellent yield (>80%). The present method is superior to others currently available due to its relatively short reaction times and excellent yields.

Full text of DOI:10.1055/s-2003-41065

SHORT PAPER
2135
An Efficient Aerobic Oxidation of Alcohols to Aldehydes and Ketones with
TEMPO/Ceric Ammonium Nitrate as Catalysts
Aerobic
O
xida
u
tion of Alco
n
hols to
A
lde
h
g
ydes and Ketones Soo Kim,* Hyun Chul Jung
Department of Chemistry and Center for Chemical Dynamics, Inha University, Incheon 402-751, South Korea
E-mail: sungsoo@inha.ac.kr
Received 30 May 2003; revised 4 July 2003
Table 1 Oxidation of sec-Phenethyl Alcohol under Various Condi-
tionsa
Abstract: Secondary benzylic alcohols with an alkyl chain are ox-
idized faster than simple benzyl alcohols. However the reaction
time is prolonged, when the alkyl chain is replaced by a bulky phe-
nyl ring such as benzhydrol and 9-hydroxyfluorene. All the benzyl
and benzylic alcohols give yields >90%. Allylic alcohols without
steric hindrance react faster to give excellent yield (>80%). The
present method is superior to others currently available due to its
relatively short reaction times and excellent yields.
O
OH
CH3
CH3
CH3CN (6mL)
(3 mmol)
b
Key words: air oxidation, TEMPO, CAN, benzylic alcohols, allyl-
ic alcohols
Entry
CAN
(mol%)
TEMPO O2
(mol%)
Time
Yield
(%)
N.R.c
5d
1
2
3
4
5
–
10
–
O2
O2
–
1 h
The oxidation of alcohols into their corresponding alde-
hydes and ketones is one of the most important processes
in organic synthesis. Recently, 2,2,6,6-tetramethylpipe-
ridinyl-1-oxyl (TEMPO)1 has been frequently employed
as the choice catalyst for the mild and selective oxidation
of alcohols. N-Oxoammonium salts can be used
stoichiometrically2,3 or generated in a catalytic manner4–11
in situ by reacting TEMPO with numerous oxidants. The
oxidants include sodium bromite,4 sodium hypochlorite,5
N-chlorosuccinimide,6 electrooxidation,7 [bis(acetoxy)io-
do]benzene,8 dimethylsulfoxide/cyanuric acid,9 oxone,10
H5IO611 and O2/TEMPO12. CAN itself is a well known ox-
idizing agent that oxidizes secondary alcohols into
ketones13–15 or benzylic groups into aldehydes.16–18 Aero-
bic O2 oxidation of alkyl malonates into ketomalonates19
employs a catalytic amount of CAN. Herein, we report the
aerobic O2 oxidation of benzylic and allylic alcohols using
TEMPO and CAN.
20
20
10
10
1.5 h
1.5 h
1 h
10
10
10
40
O2
O2
11
1 h
99
a All the reactions except for entry 4 were in CH3CN at reflux. Entry
4 was carried out at r.t.
b O2 is bubbled in all the reactions except for entry 3. Entry 3 is reacted
in air without O2 bubbling.
c No reaction occurs because the real oxidizing agent should be the
oxoammonium salt instead of the nitroxyl radical.
d CAN itself has been used as an oxidant13–18 that could be responsible
for the small yield of the ketone.
bond dissociation energy outweighs the moderate steric
hindrance in determining the rate of the oxidative process.
Steric requirement can nonetheless become important
enough to reduce the reaction rate when the alkyl chain is
replaced by a bulky phenyl ring (Compare the reaction
time of between entries 4–7 and entries 8, 9). Several al-
lylic system (entries 10–13) also give an excellent yield
that is a little lower than benzylic alcohols (entries 4–9).
Substituted allylic alcohol (entry 14) gave a good yield
with comparatively longer reaction period. In compari-
sion with previous results where TEMPO is used as a cat-
alyst (entries 1–5,10,11, and 13 of Table 2), the current
system shows much reduced reaction times.12
sec-Phenethyl alcohol is chosen for several control exper-
iments to determine the role of each reagent (Table 1).
CAN and TEMPO are the most important species without
which no reaction occurs (entry 1) or the oxidation takes
place to a very small extent (entry 2). Without O2 evolu-
tion, the oxidation gives only 40% of acetophenone (entry
3). Reflux of CH3CN is also required to obtain decent
yields (entry 4). An excellent oxidative process is de-
scribed with entry 5.
Primary benzyl alcohols (Table 2, entries 1–3) react
smoothly (2.5 h) to give the corresponding aldehydes.
However, secondary benzylic alcohols (entries 4–7) are
oxidized much faster (20 min–1 h). This may indicate that
The oxidation mechanism can be rationalized as shown
Scheme 1. Dioxygen is reduced to H2O by oxidation of
Ce3+ into Ce4+. TEMPO can be oxidized to N-oxoammo-
nium cation with the aid of Ce4+/Ce3+. N-Oxoammonium
cation then oxidizes the alcohol to give the carbonyl com-
pound.
SYNTHESIS 2003, No. 14, pp 2135–2137
0
2.
1
0
.
2
0
0
3
Advanced online publication: 24.09.2003
DOI: 10.1055/s-2003-41065; Art ID: F04803SS.pdf
© Georg Thieme Verlag Stuttgart · New York

2136
S. S. Kim, H. C. Jung
SHORT PAPER
Table 2 Aerobic Oxidaiton of Alcohols with TEMPO/CAN
Table 2 Aerobic Oxidaiton of Alcohols with TEMPO/CAN
(continued)
O
OH
O
OH
CAN (10–20 mol%), TEMPO (10 mol%)
O2, CH3CN, reflux
CAN (10–20 mol%), TEMPO (10 mol%)
O2, CH3CN, reflux
R1
R2(H)
R1
R2(H)
R1
R2(H)
R1
R2(H)
Substrate
3 mmol
CAN
0.3~0.6 mmol
TEMPO
0.3 mmol
CH3CN
6 ml
O2
Bubbling
Substrate
3 mmol
CAN
0.3~0.6 mmol
TEMPO
0.3 mmol
CH3CN
6 ml
O2
Bubbling
Entry Substrate
1
Time
Temp. Yield (%)a
(°C)
Entry Substrate
Time
Temp. Yield (%)a
(°C)
2 h
4 h
6 h
10 h
15 h
2.5 h
82
25
100
20
92b
O
12
13
1 h
82
83
OH
9412a 9912b 9812c
9912b
OH
9812c
15 min
18.5 h
24 h
82
25
65
86
OH
65
7112f
012a
7512f
100
9012h
2
2 h
6 h
6 h
82
100
20
93
OH
OH
9912b
9912c
14
7 h
82
75
OH
H3C
3
2.5 h
6 h
1.5 h
6 h
82
100
90
92
9312b
9312e
9712h
O2N
a Isolated yield.
100
b10mol% CAN was used. The rest of the reactions employ 20 mol%
of CAN.
4
1 h
6 h
6 h
42 h
4 h
1 h
82
100
20
65
100
100
99b
OH
9812b
9912c
7212f
9312h
89 12i
O
1/2 O2
+
N
Ce4+
5
6
20 min
1 h
82
82
90b
OH
O
a
OH
H3CO
Ce3+
H2O
N
O
98
OH
-H+
a.
2
+
+
7
8
30 min
30 h
2.8 h
82
65
100
94
N
N
OH
N
O
9112f
8812i
OH
O
Scheme 1
3.5 h
2 h
82
82
99
99
OH
In conclusion, the combination of TEMPO/CAN can be
used for the effective oxidation of most of benzyl, benzyl-
ic, and allylic alcohols into their corresponding carbonyl
compounds. Steric hindrance has however been observed
with some substituted allylic system. Aliphatic alcohols,
such as cyclohexanol show no reactivity towards the oxi-
dative process.
9
OH
10
3 h
2.75 h
3 h
1 h
20 h
82
25
40
90
65
81
OH
9312a
9912c
7912e
7512f
Oxidation; General Procedure
Alcohol (3 mmol), CAN (0.6 mmol) and TEMPO (0.3 mmol) were
dissolved in CH3CN (6mL) in a three-neck flask equipped with a
condenser and magnetic bar. This mixture was heated at 100 °C
with an oil bath under a continuous stream of O2. When the reaction
was complete, H2O (20mL) was added and the resulting mixture ex-
tracted with CH2Cl2 (3 × 30mL). The combined CH2Cl2 layer was
washed with water, dried over MgSO4, and the solvent was removed
11
1 h
29 h
82
65
94
OH
7812f
Synthesis 2003, No. 14, 2135–2137 © Thieme Stuttgart · New York

SHORT PAPER
Aerobic Oxidation of Alcohols to Aldehydes and Ketones
2137
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(s, 3 H).
Acknowledgment
The authors warmly thank Korea Science and Engineering Founda-
tion for the financial support (R01-2001-00057).
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Synthesis 2003, No. 14, 2135–2137 © Thieme Stuttgart · New York