Vanadium-catalyzed chlorination under molecular oxygen

Article abstract of DOI:10.1016/j.jinorgbio.2015.01.015

A catalytic chlorination of ketones was performed by using a vanadium catalyst in the presence of Bu₄NI and AlCl₃ under atmospheric molecular oxygen. This catalytic chlorination could be applied to the chlorination of alkenes to give the corresponding vic-dichlorides. AlCl₃ was found to serve as both a Lewis acid and a chloride source to induce the facile chlorination. A combination of Bu₄NI and AlI₃ in the presence of a vanadium catalyst under atmospheric molecular oxygen induced the iodination of ketones.

Full text of DOI:10.1016/j.jinorgbio.2015.01.015

JIB-09659; No of Pages 4
Journal of Inorganic Biochemistry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Journal of Inorganic Biochemistry
journal homepage: www.elsevier.com/locate/jinorgbio
Vanadium-catalyzed chlorination under molecular oxygen
Toshiyuki Moriuchi ⁎, Yasuhiro Fukui , Satoshi Kato , Tomomi Kajikawa , Toshikazu Hirao a,b,⁎⁎
a,
a
a
a
a
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan
JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
b
a r t i c l e i n f o
a b s t r a c t
Available online xxxx
4 3
A catalytic chlorination of ketones was performed by using a vanadium catalyst in the presence of Bu NI and AlCl
under atmospheric molecular oxygen. This catalytic chlorination could be applied to the chlorination of alkenes
Keywords:
to give the corresponding vic-dichlorides. AlCl was found to serve as both a Lewis acid and a chloride source to
3
Vanadium catalyst
Chlorination
Iodination
Molecular oxygen
Lewis acid
4 3
induce the facile chlorination. A combination of Bu NI and AlI in the presence of a vanadium catalyst under
atmospheric molecular oxygen induced the iodination of ketones.
©
2015 Elsevier Inc. All rights reserved.
1
. Introduction
2. Experimental
Halogenation reaction is one of the most important reactions in the
2.1. General materials and experimental procedures
field of organic synthesis, providing versatile precursors and substrates
in a variety of coupling reactions. Haloperoxidases are enzymes that
All reagents and solvents were purchased from commercial sources
catalyze the oxidation of halide ions in the presence of H
O
2 2
as an oxi-
and were further purified by the standard methods, if necessary. 1
H
dant [1–5]. Haloperoxidases have attracted extensive interest due to
their capability to halogenate a range of organic compounds. Various
bromination reactions mimicking a catalytic activity of vanadium
bromoperoxidase [6], which is a naturally occurring enzyme found in
marine algae, have been reported [7–17]. Tungsten [18] or molybdenum
3
NMR spectra were recorded in CDCl on a JNM-ECS 400 (400 MHz)
spectrometer. Chemical shifts were determined by using of
tetramethylsilane as an internal standard.
2.2. General procedure for vanadium-catalyzed chlorination under
atmospheric molecular oxygen
[19] complexes have been also demonstrated to serve as a bromination
catalyst in the presence of stoichiometric hydrogen peroxide. However,
these oxidative bromination systems require a stoichiometric amount
of a strong oxidant to generate the bromonium-like species. Some cata-
lytic oxidative bromination reactions with molecular oxygen as a termi-
nal oxidant instead of a strong oxidant have been achieved [20–24].
Recently, we have performed the combination of a vanadium catalyst,
a bromide salt, and a Brønsted acid or a Lewis acid in the presence of
molecular oxygen induces catalytic oxidative bromination of various
arenes, alkenes, alkynes, and ketones without the usage of a strong ox-
idant [25–27]. These findings prompted us to develop an efficient halo-
genation method. In this paper, we report the catalytic chlorination
reaction of ketones and alkenes without a need of a strong oxidant by
In a 5 mL three-necked flask, Bu
4
NI (111 mg, 0.3 mmol), AlCl
3
i
(40 mg, 0.3 mmol), and VO(O Pr)
3
(15 μL, 0.063 mmol) were placed.
The flask was evacuated and backfilled with molecular oxygen. To the
mixture, acetonitrile (1 mL) and a substrate (0.25 mmol) were added.
The mixture was stirred at 80 °C under atmospheric molecular oxygen,
followed by treatment with 1:1 mixture of saturated Na
solution and saturated NaHCO aqueous solution, and extraction with
ether. The organic layer was dried over MgSO , filtered, and evaporated.
2 2 3
S O aqueous
3
4
1,3,5-Trimethoxybenzene or 1,2,4,5-tetramethylbenzene was added as
1
an internal standard, and H NMR analysis was performed to determine
an NMR yield. Spectral data of the products were identical with those of
commercially available and authentic samples.
4 3
using a vanadium catalyst in the presence of Bu NI and AlCl with mo-
lecular oxygen as a terminal oxidant.
2.3. General procedure for vanadium-catalyzed iodination under atmospheric
molecular oxygen
⁎
⁎
Corresponding author.
Correspondence to: T. Hirao, Department of Applied Chemistry, Graduate School of
4 3
In a 5 mL three-necked flask, Bu NI (111 mg, 0.3 mmol), AlI
122 mg, 0.3 mmol), and NH VO (2.9 mg, 0.025 mmol) were placed.
4 3
The flask was evacuated and backfilled with molecular oxygen. To the
mixture, acetonitrile (1 mL) and a substrate (0.25 mmol) were added.
⁎
(
Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan.
E-mail addresses: moriuchi@chem.eng.osaka-u.ac.jp (T. Moriuchi),
hirao@chem.eng.osaka-u.ac.jp (T. Hirao).
http://dx.doi.org/10.1016/j.jinorgbio.2015.01.015
0162-0134/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: T. Moriuchi, et al., Vanadium-catalyzed chlorination under molecular oxygen, J. Inorg. Biochem. (2015), http://
dx.doi.org/10.1016/j.jinorgbio.2015.01.015

2
T. Moriuchi et al. / Journal of Inorganic Biochemistry xxx (2015) xxx–xxx
Table 1
Table 3
Catalytic chlorination of propiophenone by using vanadium catalyst/Bu
system.
4
NI/AlCl
3
/O
2
4 3 4 3 2
Catalytic chlorination of ketones by using cat. NH VO /Bu NI/AlCl /O system.
Â
Products
NMR yield (%)
Entry
1
Substrate
Time (h)
NMR yield (%)
V cat.
x (mol%)
Entry
1
V cat.
Solv.
Time (h)
2
a
3a
0
0
0
0
0
0
0
0
3
9
0
0
NH VO3
10
–
MeCN
MeCN
24
24
24
24
24
24
24
24
24
24
24
36
60
0
4
2
3a
–
36
48
49
53
3
4
NH VO3
10
10
10
10
10
20
20
20
20
20
MeCN
DMEb
CPMEc
7
4
2
3
4
NH VO3
31
36
0
4
5
NH VO3
4
6d
7e
8
ether
4
NH VO3
NH VO3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
64
77
90
69
70
98
4
NH VO3
4
3
6
55
63
3
i
9
VO(O Pr)3
1
1
1
0
1
2
VO(acac)2
VOCl3
4
NH VO3
4
a
b
c
Ar atmosphere.
,2-Dimethoxyethane.
Cyclopentyl methyl ether.
Room temperature.
24
trace
1
d
e
4 3
200 mol% of Bu NI and AlCl were used.
2.4. Gram-scale reaction of propiophenone
In a 50 mL three-necked flask, Bu
4
NI (4.43 g, 12 mmol), AlCl
3
(1.60 g,
i
The mixture was stirred at 80 °C under atmospheric molecular oxygen,
followed by treatment with 1:1 mixture of saturated Na aqueous
solution and saturated NaHCO aqueous solution, and extraction with
ether. The organic layer was dried over MgSO , filtered, and evaporated.
,2,4,5-Tetramethylbenzene was added as an internal standard, and H
NMR analysis was performed to determine an NMR yield. Spectral data
of the products were identical with those of commercially available and
authentic samples.
12 mmol), and VO(O Pr) (472 μL, 2.0 mmol) were placed. The flask was
3
S O
2 2 3
evacuated and backfilled with molecular oxygen. To the mixture, aceto-
nitrile (30 mL) and propiophenone (1.33 mL, 10 mmol) were added.
The mixture was stirred at 80 °C under atmospheric molecular oxygen
3
4
1
1
for 24 h, followed by treatment with 1:1 mixture of saturated Na
aqueous solution and saturated NaHCO aqueous solution, and extrac-
tion with ether. The organic layer was dried over MgSO , filtered, and
2 2 3
S O
3
4
evaporated. The residue was chromatographed on a silica gel column
eluting with hexane and dichloromethane to give 1.32 g (78% yield) of
2-chloro-1-phenylpropan-1-one.
3. Results and discussion
Table 2
The effect of a halide source and aluminium halide in catalytic halogenation of
propiophenone by using cat. NH VO .
4 3
α-Halocarbonyl compounds are regarded as important precursors
for various transformations employed in organic and pharmaceutical
syntheses. The chlorination reaction of propiophenone in the presence
of 10 mol% of NH VO , 120 mol% of Bu NI, and 120 mol% of AlCl as a
4 3 4 3
Â
Lewis acid in MeCN at 80 °C for 24 h under atmospheric molecular oxy-
gen was performed (Table 1, entry 1). The chlorination reaction
proceeded well to afford the α-chlorocarbonyl compound 2a in 60%
NMR yield (%)
4 3
yield. No chlorination product was obtained in the absence of NH VO
Entry
Halide source
AlY3
2
a
3a
0
(entry 2). This catalytic chlorination reaction was not effectively per-
formed under argon atmosphere (entry 3). The chlorination reaction
in other solvents, such as dimethoxyethane (DME), cyclopentyl methyl
ether (CPME), and ether resulted in a slightly decreased yield (entries
1
2
3
4
Bu NI
AlCl3
AlCl3
AlI3
60
7
4
KI
9
Bu NCl
58
5
16
4
4
–6). The use of 200 mol% of Bu
show a drastically enhanced yield (entry 7). With an increased amount
(20 mol%) of NH VO , the α-chlorocarbonyl derivative 2a was produced
in a good yield (entry 8). Highly active catalysis was observed with
4 3
NI, and 200 mol% of AlCl did not
Bu NCl
AlCl3
AlI3
0
4
33a
5
Bu NI
0
4
3
4
6b
49a
Bu NI
AlI3
0
4
i
3 2 3
VO(O Pr) (entry 9) although VO(acac) and VOCl exhibited a similar
a
catalytic activity (entries 10–11). The α-chlorocarbonyl compound 2a
was obtained quantitatively by extending the reaction time (entry 12).
Benzoic acid was obtained as a by-product.
Reaction time: 48 h.
b
Please cite this article as: T. Moriuchi, et al., Vanadium-catalyzed chlorination under molecular oxygen, J. Inorg. Biochem. (2015), http://
dx.doi.org/10.1016/j.jinorgbio.2015.01.015

T. Moriuchi et al. / Journal of Inorganic Biochemistry xxx (2015) xxx–xxx
3
Table 4
proceeded to give 3a in 33% yield (entry 5). Lewis acidity of AlX
idation potentials of halide ions are considered to be key factors in this
vanadium-catalyzed chlorination. Extending the reaction time led to a
and ox-
3
i
Catalytic chlorination of ketones by using cat. VO(O Pr)
/Bu NI/AlCl /O
3 4 3 2
system.
16% increase in yield (entry 6).
Â
The chlorination reaction of 4′-methoxyacetophenone in the pres-
4 3 4 3
ence of 20 mol% of NH VO , 120 mol% of Bu NI, and 120 mol% of AlCl
Products
NMR yield (%)
in MeCN at 80 °C for 36 h under atmospheric molecular oxygen afforded
the α-chlorocarbonyl compound 2b in 49% yield as a major product
with the dichlorination product 2bb in 3% yield (Table 3, entry 1). The
longer reaction time led to a slightly increased yield (entry 2). In the
case of 4′-chloroacetophenone, the α-chlorination product 2c was ob-
tained in 55% yield (entry 3). β-Keto esters such as ethyl benzoylacetate
underwent the chlorination to give the monochlorinated product 2d
Entry
1
Substrate Time (h)
24
44
13
1
with a trace amount of the monochlorinated product 3d (entry 4).
i
2
3
A catalytic chlorination of ketones by using cat. VO(O Pr)
/Bu
NI/
3
4
3 2
AlCl /O system was examined (Table 4). The chlorination reaction of
′-methoxyacetophenone proceeded to afford the α-chlorination product
b in a moderate yield and the dichlorination product 2bb in 13% yield
with a trace amount of the α-iodination product 3b (entry 1). VO(O Pr)
4
2
2
2
5
4
66
84
13
12
4
4
i
3
4 3
showed higher efficiency than NH VO . 4′-Chloroacetophenone was chlo-
rinated to give the monochlorinated product 2c in 66% yield and the
dichlorination product 2cc in 13% yield together with a small amount of
the α-iodinated product 3c (entry 2). Starting from acetophenone, the
α-chlorinated product 2e was obtained in 84% yield with the
dichlorinated product 2ee in 12% yield and a small amount of the α-
iodinated product 3e (entry 3). This catalytic chlorination could be
applied to the chlorination of alkenes (Table 5). 1-Decene underwent
the selective vic-chlorination to afford 1,2-dichlorodecane (5a) in 72%
yield (entry 1). Catalytic chlorination of 5-hexene-1-ol proceeded
smoothly to give the dichlorinated product 5b in 78% yield with the
hydroxy group intact (entry 2). Allylbenzene was converted into the
dichloride in 87% yield (entry 3).
It is noteworthy to mention that a gram-scale reaction underwent
successfully to give the expected chlorinated product in a high yield,
as exemplified by the α-chlorination of propiophenone in 78% isolated
yield as shown in Scheme 1. Starting from the α-iodo ketone 3a, the
α-chloro ketone 2a was obtained as a sole product selectively
The effect of a halide source and aluminium halide in catalytic halo-
genation of propiophenone by using NH VO as a catalyst was exam-
ined (Table 2). KI was not effective in the chlorination (entry 2). The
combination of Bu NCl and AlI induced the formation of the α-
chlorination product 2a in 58% yield together with the α-iodination
one 3a in 16% yield (entry 3). The use of Bu NCl and AlCl showed no
NI and AlI , the iodination reaction
4
3
4
3
4
3
promising results (entry 4). With Bu
4
3
(Scheme 2). Thus, the key intermediate for the chlorination is proposed
Table 5
to be the α-iodo ketone 3a, which is considered to be generated by the
oxidation of an iodide ion via oxygen-atom transfer of an oxovanadium
species activated by a Lewis acid [26,27].
i
Catalytic chlorination of alkenes by using cat. VO(O Pr)
/Bu NI/AlCl /O
3 4 3 2
system.
Â
4. Conclusions
Products
NMR yield (%)
The catalytic chlorination reaction of ketones without the use of a
Entry
1
Substrate
Time (h)
a
strong oxidant was achieved by using a commercially available inex-
pensive ligand-free vanadium catalyst in the presence of Bu
NI and
AlCl with molecular oxygen as a terminal oxidant, in which AlCl was
4
3
3
found to serve as both a Lewis acid and a chloride source to induce the
facile chlorination. This catalytic system was also demonstrated to be
capable of inducing the catalytic chlorination of alkenes to afford the
30
24
24
72 (66)
4 3
corresponding vic-dichlorides. The combination of Bu NI and AlI in
the presence of a vanadium catalyst under atmospheric molecular oxy-
gen was found to induce the iodination of ketones. Studies on the reac-
tion mechanism and synthetic versatility, and application of this
practical method to other reactions are now in progress.
2
3
78 (65)
87 (66)
Acknowledgment
This work was supported partly by a Grant-in-Aid for Scientific
Research ACT-C program of the Japan Science and Technology Agency
(JST). Thanks are due to the Analytical Center, Graduate School of
i
Engineering, Osaka University. The donation of VO(O Pr)
Nichia corporation is also acknowledged.
3
from the
a
Numbers in parentheses show isolated yields.
Please cite this article as: T. Moriuchi, et al., Vanadium-catalyzed chlorination under molecular oxygen, J. Inorg. Biochem. (2015), http://
dx.doi.org/10.1016/j.jinorgbio.2015.01.015

4
T. Moriuchi et al. / Journal of Inorganic Biochemistry xxx (2015) xxx–xxx
Scheme 1. Gram-scale chlorination of propiophenone.
Scheme 2. Catalytic chlorination reaction of 2-iodo-1-phenylpropan-1-one.
[
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Please cite this article as: T. Moriuchi, et al., Vanadium-catalyzed chlorination under molecular oxygen, J. Inorg. Biochem. (2015), http://
dx.doi.org/10.1016/j.jinorgbio.2015.01.015