New efficient organocatalytic oxidation of benzylic compounds by molecular oxygen under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2006.01.028

Efficient aerobic oxidation of benzylic compounds has been achieved under no irradiation using a new organocatalytic system in the presence of acridine yellow and N-hydroxyphthalimide with assistance of a catalytic amount of molecular bromine. Various substrates, especially alkylaromatics, were effectively oxygenated to the corresponding carbonyl compounds with molecular oxygen as oxidant under mild conditions. For instance, indan was oxidized with 92% conversion and 79% selectivity for 1-indanone under 0.3 MPa of O₂ at 75°C.

Full text of DOI:10.1016/j.tetlet.2006.01.028

Tetrahedron Letters 47 (2006) 1763–1766
New efficient organocatalytic oxidation of benzylic compounds
by molecular oxygen under mild conditions
Xinli Tong, Jie Xu,* Hong Miao and Jin Gao
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Graduate School of the Chinese Academy of Sciences,
Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China
Received 14 October 2005; revised 10 January 2006; accepted 11 January 2006
Available online 26 January 2006
Abstract—Efficient aerobic oxidation of benzylic compounds has been achieved under no irradiation using a new organocatalytic
system in the presence of acridine yellow and N-hydroxyphthalimide with assistance of a catalytic amount of molecular bromine.
Various substrates, especially alkylaromatics, were effectively oxygenated to the corresponding carbonyl compounds with molecular
oxygen as oxidant under mild conditions. For instance, indan was oxidized with 92% conversion and 79% selectivity for 1-indanone
under 0.3 MPa of O2 at 75 °C.
Ó 2006 Elsevier Ltd. All rights reserved.
Oxidation is one of the most fundamental transforma-
tions in organic chemistry. Direct benzylic oxidation is
the foundation of many current important industrial
and fine-chemical processes,1 which is utilized in a
diverse field from natural product chemistry to ‘bucky-
bowl’ synthesis.2 Traditionally, a stoichiometric amount
of oxidant such as manganese dioxide, chromic acid,
potassium dichromate, or selenium dioxide was
employed for these transformations.3 In recent years,
the use of molecular oxygen as terminal oxidant has
received great attention for both economical and environ-
mental benefits. Simultaneously, many highly efficient
systems have been developed for catalytic aerobic ben-
zylic oxidation. For example, metallic catalyst systems
containing cobalt, ruthenium, copper, or iron element
have been reported.4–7 Typically, the extensive research
of using metalloporphyrins as catalysts in the oxidation
process has been carried through by several groups.8
Furthermore, the attractive work by Ishii and Einhorn
showed that the benzylic oxidation process could be ful-
filled with the combination of N-hydroxyphthalimide
(NHPI) and metal compound (or aldehydes).9 However,
due to metallic toxicity and the high expense, researches
have been concentrated on developing nonmetallic
organocatalytic system.10 Recently, our group reported
a biomimetic aerobic oxidation system, in which some
hydrocarbons were successfully oxidized with a non-
metallic combination of anthraquinones, NHPI, and
HY zeolite.11 On the other hand, in photocatalytic oxi-
dation, acridines analogues (e.g., 9-mesityl-10-methyl-
acridinium ion), which have been used as efficient organo-
catalysts for highly selective oxidation of hydrocarbons
under light irradiation,12 can act as active radical cations
via photoinduced electron transfer and sequentially acti-
vate oxygen and substrates to achieve oxidation process.
But these types of acridines compounds have never been
described for hydrocarbons oxidation without irradia-
tion. In this letter, by utilizing the electron-transferring
character of acridine yellow, we emphasize a new organo-
catalytic system of acridine yellow and NHPI with the
assistance of molecular bromine (Br2) for a highly effi-
cient aerobic benzylic oxidation under mild and no radi-
ant conditions. Thereinto, choosing molecular bromine
as a co-catalyst is based on the fact that it can simply
oxidize nitrogen atom to radical cation through one
electron oxidation;13 Moreover, molecular bromine has
exhibited outstanding promotion action in some oxida-
tion processes.14
In a first series of experiments, we have investigated the
aerobic oxidation of indan (1) as a model substrate
(Scheme 1) under various experimental conditions
(Table 1). The experiments were performed in a sealed
Teflon-lined stainless steel autoclave equipped with
magnetic stirring and automatic temperature control.
It was observed that only 3% of indan was oxidized
Keywords: Benzylic oxidation; Organocatalysis; Molecular oxygen;
Acridine yellow.
*
Corresponding author. Tel./fax: +86 0411 84379245; e-mail:
xujie@dicp.ac.cn
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.028

1764
X. Tong et al. / Tetrahedron Letters 47 (2006) 1763–1766
were tested instead of acridine yellow, no high effective-
O
OH
organocatalytic
system
ness was observed in the oxidation and it could be
ascribed to the matching effect of electron transferring
(entries 7–9).
+
0.3MPa O2
C
50 , 5 h
˚
(1)
(3)
(2)
In order to further understand the reaction characters,
N-bromosuccinimide (NBS) or sodium bromide (NaBr)
was employed instead of molecular bromine as a co-cat-
alyst. The conversion was reduced to 61% or 57% under
similar conditions (entries 10 and 11 in Table 1). On the
other hand, the effect of temperature on the oxidation of
1 was investigated and is outlined in Figure 1. It shows
that the selectivity for 2 was increased and the selectivity
for peroxide was reduced gradually along with the
increase of temperature from 35 to 75 °C. At 75 °C,
92% conversion with 79% selectivity for 2, 18% selectiv-
ity for 3 was observed (entry 12).
Scheme 1. Oxidation of indan with molecular oxygen.
under 0.3 MPa of O2 at 50 °C for 5 h when 7.5 mol %
NHPI was used separately (entry 1), and nearly no reac-
tion occurred when only 2.5 mol % acridine yellow was
used (entry 2). When acridine yellow and NHPI were
coupled as a catalytic system, the conversion was
improved to 29% under the same reaction condition
(entry 3). To our surprise, further research investigation
showed that an 87% conversion and 54% selectivity for
1-indanone (2) were obtained when 2.5 mol % Br2 was
added as a co-catalyst (entry 4). In succession, we inves-
tigated the oxidation of indan with only ‘NHPI–Br2’ or
‘acridine yellow–Br2’ under the same conditions. Never-
theless, just 4% or 3% of indan was, respectively, oxi-
dized (entries 5 and 6). These data clearly showed that
the combination of ‘NHPI–acridine yellow–Br2’ system
could effectively promote oxidation of 1. As a result,
we found when the content of NHPI–acridine yellow–
Br2 was 7.5–2.5–2.5 mol %, the selective catalytic oxida-
tion efficiently proceeded and the result was satisfying. It
is worth noting that when other acridines compounds
A variety of benzylic compounds were next effectively
oxidized by dioxygen using our organocatalytic system
(Table 2). Tetralin was similarly oxidized with 93% con-
version and 95% selectivity for 1-tetralone (entry 1).
When ethylbenzene was oxidized, 67% conversion and
94% selectivity for acetophenone were obtained after
5 h (entry 2). Moreover, 4-ethylbenzonitrile was
oxidized with 51% conversion and 99% selectivity for
4-acetylbenzonitrile under same conditions (entry 3).
When diphenylmethane was oxidized, 65% conversion
Table 1. Oxidation of indan in different catalyst combinationsa
Entry
Catalystb
Conversionc
Product selectivity
Indanone
Indanol
Peroxide
1
2
3
4
5
6
7
8
NHPI
Acridine yellow
3
0
29
87
4
12
—
23
14
35
21
22
19
18
23
23
18
21
—
33
54
34
72
13
61
52
32
65
79
67
—
44
32
31
7
65
20
30
45
12
3
Acridine yellow+NHPI
Acridine yellow+NHPI+Br2
NHPI+Br2
Acridine yellow+Br2
Acridine+NHPI+Br2
Acridine orange+NHPI+Br2
Acridine red+NHPI+Br2
Acridine yellow+NHPI+NBS
Acridine yellow+NHPI+NaBr
Acridine yellow+NHPI+Br2
3
19
12
39
61
57
92
9
10
11
12d
a Reaction conditions: Indan was performed on a 1 mL scale, in the presence of NHPI (7.5 mol %), acridine yellow or analogues (2.5 mol %), Br2
(2.5 mol %), in 10 mL CH3CN, pressure = 0.3 MPa, time = 5 h, temperature = 50 °C.
b The corresponding chemical structures of some compounds:
O
CH3
NH2
CH3
NH2
N OH
N
N
O
N-hydroxyphthalimide
Acridine yellow
Acridine
NH
O+
Acridine red
NH
N
N
N
Acridine orange
.
c The data were obtained by GC and GC–MS analysis using 1,3-dichlorobenzene as an internal standard.
d Temperature was increased to 75 °C.

X. Tong et al. / Tetrahedron Letters 47 (2006) 1763–1766
1765
100
95
90
85
80
75
70
65
60
55
50
45
was performed with this catalytic system, the reaction
was very slow and the conversion was less than 10%
under the same conditions. Therefore, a direct pathway
leading from alkylaromatics to the corresponding
ketones seemed likely.15
Conversion---A
Selectivity ---B
A
B
Here, a hypothetical reaction mechanism is proposed for
indan oxidation (Scheme 2). Firstly, acridine yellow is
converted to cation radical through a single-electron
oxidation of nitrogen atom by molecular bromine (step
1), and then the cation radical impels generation of
phthalimide N-oxyl radical (PINO) via electron and pro-
ton transfer between cation radical and NHPI (step 2).
The final step involves the hydrogen atom abstraction
from indan by PINO, and the resulting indan radical
being trapped by dioxygen provides peroxy radical,
which is eventually converted into products through
hydroperoxide (step 3). Further investigations on the
direct information of acridine yellow cation radical
and selective transformation process in the reaction
are underway.
30
40
50
60
70
80
Temperature/ oC
Figure 1. The temperature effect on the oxidation of indan.
and 99% selectivity for benzophenone were obtained at
100 °C for 20 h (entry 4). Acenaphthene was oxidized
with 70% conversion and 88% selectivity for acenaphth-
ylenone after 24 h (entry 5). From these results, we can
see that the ketones were obtained with higher efficiency
and selectivity under milder reaction conditions over
conventional benzylic oxidation systems when alkylaro-
matics were oxidized by our organocatalytic system.3–8
Meanwhile, when the oxidation of 1-phenylethanol
In summary we have developed a new catalytic system
for aerobic oxidation using NHPI and acridine yellow
with assistance of a catalytic amount of molecular
bromine. This system allows efficient oxidation of
benzylic compounds under mild conditions without
any metal component. The extension of this approach
is underway.
Table 2. Oxidation of various substrates by ‘NHPI–acridine yellow–Br2’ systema
Entry
Substrate
Conversionb
Product selectivityc
1-Tetralol
1
2
3
4d
5e
Tetralin
93
67
51
65
70
1-Tetralone
Acetophenone
4-Acetylbenzonitrile
Benzophenone
Acenaphthylenone
95
94
99
99
88
4
5
1
1
12
Ethylbenzene
4-Ethylbenzonitrile
Diphenylmethane
Acenaphthene
1-Phenylethanol
4-(1-Hydroxyethyl)benzonitrile
Diphenylmethanol
Dihydroacenaphthylenol
a Reaction conditions: Indan was performed on a 1 mL scale, in the presence of NHPI (7.5 mol %), acridine yellow or analogues (2.5 mol %), Br2
(2.5 mol %), in 10 mL CH3CN, pressure = 0.3 MPa, time = 5 h, temperature = 75 °C.
b The data were obtained by GC and GC–MS analysis using 1,3-dichlorobenzene as an internal standard.
c Selectivity for peroxide was left out owing to less than 1%.
d Oxidation of diphenylmethane was employed at 100 °C under 0.3 MPa of O2 for 20 h.
e Acenaphthene was performed on a 0.77 g scale for oxidation at 100 °C under 0.3 MPa of O2 for 24 h.
CH3
NH2
H3C
H2N
CH3
NH2
H3C
H2N
+ Br2
- Br-
(1)
(2)
(3)
N
N
(A
)
(A)
O
+ A
NHPI
PINO
PINO:
+ O2
N O
-(A + H+)
O
O
OH
A + Br-
- Br2
+ PINO
- NHPI
+
Scheme 2. Proposed mechanisms for indan oxidation.

1766
X. Tong et al. / Tetrahedron Letters 47 (2006) 1763–1766
Legros, J.; Bolm, C. Adv. Synth. Catal. 2005, 347, 703–
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Natural Science Foundation of China (Project
20233040 and 20473088) and the National High Tech-
nology Research and Development Program of China
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