Room-temperature direct benzylic oxidation catalyzed by cobalt(II) perchlorate

Article abstract of DOI:10.1016/j.tetlet.2016.10.049

Aromatic ketones were synthesized from alkylbenzene derivatives through a novel method that employs cobalt(II) perchlorate as catalyst and oxone as oxidant. The reaction smoothly proceeded at room temperature with yields reaching 96%.

Full text of DOI:10.1016/j.tetlet.2016.10.049

Accepted Manuscript
Room-temperature direct benzylic oxidation catalyzed by cobalt(II) perchlorate
Yiwen Yang, Hongxia Ma
PII:
S0040-4039(16)31363-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.10.049
TETL 48219
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
8 August 2016
29 September 2016
14 October 2016
Please cite this article as: Yang, Y., Ma, H., Room-temperature direct benzylic oxidation catalyzed by cobalt(II)
perchlorate, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.10.049
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Tetrahedron Letters
Room-temperature direct benzylic oxidation catalyzed by cobalt(II) perchlorate
Yiwen Yang *, Hongxia Ma
College of Biological, Chemical Sciences and Engineering, Jiaxing University, 118 Jiahang Road, Jiaxing 314001, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Aromatic ketones were synthesized from alkylbenzene derivatives through a novel method that
employs cobalt(II) perchlorate as catalyst and oxone as oxidant. The reaction smoothly
proceeded at room temperature with yields reaching 96%.
2
016 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Room temperature
Direct benzylic oxidation
Cobalt(II) perchlorate
The direct oxidation of the benzylic C–H bond is one of the
most useful and significant transformations because of its
widespread applications, especially in organic synthesis. This
attractive synthetic transformation can convert relatively cheap
hydrocarbons into value-added hydroxyl and carbonyl
compounds, which are important starting materials or
intermediates in the synthesis of pharmaceuticals, agrochemicals,
Scheme 1. Direct benzylic oxidation of alkyl aromatic
compounds.
1
and natural products. Traditionally, benzylic oxidation often
requires harsh reaction conditions and stoichiometric amounts of
metal oxidants, such as potassium permanganate, potassium
dichromate, or ammonium cerium nitrate, which generate a large
2
The oxidation of diphenylmethane (1a) was chosen as a
model reaction to confirm the optimum reaction conditions.
The reaction conditions, including the catalysts, oxidants, and
solvents, were investigated. The results are summarized in
Table 1. Only a trace amount of the product 2a was obtained
when no catalyst was used (Table 1, entry 1). Catalyst
screening showed that the yield could be improved with
amount of waste. In the past few decades, much effort has been
3
devoted to this transformation; several new metal catalysts
involving Cr, Mn, Co, Bi, Ru, Rh, Re, Fe, and Au, as well as
4
metal-free oxidants,
such as 2-iodoxybenzoic acid (IBX),
NaClO/TBHP, and HBr/H O , have been developed. Although
2
2
these methods provided a feasible approach for benzylic
oxidation, most of these systems have drawbacks, such as harsh
reaction conditions, complicated or expensive metal catalysts，
low yield of main product and long reaction time. Therefore,
simple and efficient methods for the benzylic C-H oxidation that
can operate under mild reaction conditions and use readily
available, inexpensive catalysts and non-toxic oxidants are highly
desirable.
Co(ClO ) as the catalyst; other catalysts, such as Co(OAc) ,
4 2
2
CoCl , Fe(ClO ) , and Cu(ClO ) , were less effective (Table 1,
2
4 3
4 2
entries 2–6). Therefore, Co(ClO
best catalyst. Various oxidants,
)
was determined to be the
such as 3-
4 2
chlorobenzoperoxoic acid (m-CPBA), hydrogen peroxide (30%
v/v solution of H O ), tert-butyl hydroperoxide (70% v/v
2
2
solution of t-BuOOH), N-bromosuccinimide (NBS), and O2
1 atm) could not improve the product yield (Table 1, entries
, 7–11). Therefore, oxone was chosen as the ideal oxidant.
The reaction was significantly affected by the solvent (Table 1,
entries 12–18). Compared with CH CN/H O mixed solvent,
In this paper, we report a new and efficient procedure for the
synthesis of benzylic carbonyl compounds from alkyl aromatic
compounds by utilizing a readily available and inexpensive
transition metal salt, Co(ClO ) , with an efficient, inexpensive,
versatile, and environmentally benign oxidant, oxone (KHSO5).
The direct oxidation of the benzylic C–H bond at room
(
4
4
2
5
3
2
acetonitrile single solvent only afforded a trace amount of the
product 2a (Table 1, entries 12–14), because water plays an
important role in the oxidation of benzylic methylenes into
temperature is exploited (Scheme 1).
4e,6
ketones. Consequently, the effect of the amount of water in
the CH CN/H O system on the conversion was examined
3
2
(
Table 1, entries 4, 12–15). The results showed that an
improved yield could be obtained with CH CN/H O (1/1, v/v)
3
2

2
Tetrahedron
as the solvent (Table 1, entries 13); other volume ratios of
CH CN to H O were less effective as solvents. Table 1 shows
this oxidation transformation. Table 2 shows that the present
protocol was successfully applied to variety of
3
2
a
that when acetone /H O and AcOH/H O were used as solvents
instead of CH CN/H O, the yield of 2a (Table 1, entries 13,
representative benzylic reagents (Table 2, entries 1–11). The
corresponding products were obtained in moderate to
excellent yields. The diphenylmethane type substrates could
yield the corresponding products with moderate to excellent
yields between 62% and 90% (Table 2, entries 1–3). 1,2-
Diphenylethane could also afford the corresponding products
with moderate yield (Table 2, entry 4). The substrates with
one annelated aryl group or one heteroaryl group in a cyclic
structure produced the corresponding benzylic oxidation
2
2
3
2
1
6–17) was decreased. Therefore, CH CN/H O (1/1, v/v) was
3 2
determined to be the best solvent. The effect of the amount of
Co(ClO ) and oxone on the oxidation of 1a was also studied.
The results indicated that 0.1 eq Co(ClO ) and 6 eq oxone
afforded the oxidation product 2a with good yield (Table 1,
entry 13). Compared with the amount of 0.1 eq, an increase or
decrease in the amount of Co(ClO ) reduced the yield of 2a
4
2
4
2
4
2
(
Table 1, entries 18–20). When the amount of oxone is less
than 6 eq, it results in incomplete reaction, while increasing
its amount to 8 eq, may lead to further oxidation of product 2a
a
Table 2. Synthesis of aromatic ketones.
(
Table 1, entries 21–23). Finally, the optimized catalytic
system was obtained, viz., 0.1 eq Co(ClO ) as catalyst, 6.0 eq
4
2
oxone as oxidant, and CH CN/H O (1/1, v/v) as solvent at a
3
2
reaction temperature of 25 °C for a reaction time of 3 h under
air (Table 1, entry 13).
a
Table 1. Screening for optimal reaction conditions.
Yield of
Entry
Substrate (1)
Product (2)
[b]
2
(%)
1
90
72
1
b
2
b
2
Catalyst
Oxidant
(6 eq)
Yield of
Entry
Solvent (v/v)
b
(0.1 eq)
2a (%)
2
3
1
c
1
2
3
4
5
6
7
8
9
none
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
m-CPBA
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
3
3
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
CN/H
2
2
2
2
2
2
2
2
2
2
2
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
O(2/1)
trace
60
c
Co(OAc)
CoCl
Co(ClO
2
2
48
67
78
4
)
2
84
1
d
Fe(ClO
Cu(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
4
)
3
9
2d
4
4
4
4
4
4
4
)
)
)
)
)
)
)
2
2
2
2
2
2
2
trace
8
4
H
2
O
2
trace
trace
8
1
e
2e
t-BuOOH
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
NBS
5
6
60
81
O
2
(1 atm)
trace
trace
96
1
f
2
f
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
CH
CN/H
CN/H
3
CN
Co(ClO
4
)
2
CH
3
2
O (1/1)
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
4
)
)
)
)
)
2
2
2
2
2
CH
3
2
O (1/2)
75
1g
1h
2
g
4
4
4
4
2
H O
6
Acetone /H
2
O (1/1)
70
7
8
66
74
AcOH/H O (1/1)
2
30
2
h
CH
CH
CH
3
3
3
CN/H
2
O (1/1)
O (1/1)
O (1/1)
25
(0.01)
1
i
1
2
9
0
Co(ClO
4
)
2
2
Oxone
Oxone
CN/H
2
2
27
76
2i
(0.05)
9
63
65
Co(ClO
4
)
CN/H
1
j
2j
(
0.15)
2
2
2
1
2
3
Co(ClO
Co(ClO
Co(ClO
4
4
4
)
)
)
2
2
2
Oxone (2)
Oxone (4)
Oxone (8)
CH
CH
CH
3
3
3
CN/H
CN/H
CN/H
2
2
2
O (1/1)
O (1/1)
O (1/1)
11
58
63
10
1
k
2k
1
1
70
a]
Reaction conditions: 1.0 eq of 1a was stirred at 25 °C for 3 h.
Isolated yield.
1l
b
2l
a
Reaction conditions: A mixture of 1 (0.2 mmol), Co(ClO
)
4 2
(0.02 mmol),
oxone (1.2 mmol), CH
tube at 25 °C for 3 h.
CN (2 mL), and H O (2 mL) was stirred in a sealed
3 2
Under the optimal reaction conditions, a wide range of
benzylic substrates were tested to explore the generality of

b
2
3
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.
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Isolated yield.
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(
tetrahydronaphthalene (1f), 2,3-dihydro-1H-indene (1g),
isochroman (1h), and 1,3-dihydroisobenzofuran (1i) have two
–
CH – (methylene) groups attached to the benzene ring, but
2
only one benzyl group can be converted to a carbonyl group.
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oxidized to form the corresponding ketones with moderate
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5
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5
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, 61759-61774.
A plausible mechanism for the the synthesis of 2 is
depicted in Scheme 2. Initially, the reactions involve the
4
.
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3185; (b) Yang, G. Y.; Zhang, Q. H.; Miao, H.; Tong, X. L.;Xu, J.
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Eng.Chem. Res. 2016, 55, 3308-3312.
2+
oxidation of Co with oxone to generate a
situ. Then the radical reacts with H O to provide
radical. Followed by the reduction of Co with oxone, Co
radical in
7
2
8
3+
2+
7a
is regenerated. The attack of
subsequent α-H atom abstraction forms species A, which
further reacts with
Finally, oxydehydrogenation occurrs, and products (2) are
radical on substrate 1 and
9
radical to afford the intermediate B.
10
5. (a) Hull, J. F.; Balcells, D.; Sauer, E. L. O.; Raynaud, C.; Brudvig,
formed.
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1
2
32, 7605-7616; (b) Thottumkara, P.P.; Vinod, T. K. Org. Lett.
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8
9
.
.
Scheme 2. Proposed mechanism for the synthesis of 2.
1
0. Yin, L.; Wu, J.; Xiao, J.; Cao, S. Tetrahedron Lett. 2012, 53,
418-4421.
4
In summary, a mild and efficient methodology for the
direct oxidation of the benzylic C–H bond was developed in
this study. The reaction can be conducted at room temperature
to provide benzylic carbonyl products with moderate to
excellent yields. These products are important compounds in
the synthesis of pharmaceuticals, agrochemicals, and natural
products.
Acknowledgments
This study was supported by the Natural Science Foundation of
China (No. 21371079). We also thank the Center for
Instrumental Analysis at Jiaxing University, China.
References and notes
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Newhouse, T.;Baran, P. S.; Angew. Chem. Int. Ed. 2011, 50, 3362-
3
374.

4
Tetrahedron
Graphical Abstract
Room-temperature direct benzylic
oxidation catalyzed by cobalt(II)
perchlorate
Leave this area blank for abstract info.
Yiwen Yang *, Hongxia Ma

Highlights
1
2 aromatic ketones were obtained by the direct
benzylic oxidation.
The oxidation can proceed at room temperature and
it takes only 3 hours.
It employs Co(ClO ) as catalyst and oxone as
4
2
oxidant.