An efficient chlorination of aromatic compounds using a catalytic amount of iodobenzene

Article abstract of DOI:10.1016/j.cclet.2013.03.049

An efficient method was developed for chlorination of aromatic compounds with electron-donating groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the presence of 4-methylbenzenesulfonic acid in THF at room temperature for 24 h, and a series of the monochlorinated compounds was obtained in good yields. In this protocol, the catalyst iodobenzene was first oxidized into the hypervalent iodine intermediate, which then treated with lithium chloride and finally reacted with aromatic compounds to form the chlorinated compounds.

Full text of DOI:10.1016/j.cclet.2013.03.049

Chinese Chemical Letters 24 (2013) 535–538
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Chinese Chemical Letters
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Original article
An efficient chlorination of aromatic compounds using a catalytic amount of
iodobenzene
Ting-Ting Li a, Cui Xu b, Chang-Bin Xiang a, Jie Yan a,
*
a College of Chemical Engineering and Materials Sciences, Zhejiang University of Technology, Hangzhou 310032, China
b Foreign Language School, Zhejiang Shuren University, Hangzhou 310015, China
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient method was developed for chlorination of aromatic compounds with electron-donating
groups using iodobenzene as the catalyst and m-chloroperbenzoic acid as the terminal oxidant in the
presence of 4-methylbenzenesulfonic acid in THF at room temperature for 24 h, and a series of the
monochlorinated compounds was obtained in good yields. In this protocol, the catalyst iodobenzene was
first oxidized into the hypervalent iodine intermediate, which then treated with lithium chloride and
finally reacted with aromatic compounds to form the chlorinated compounds.
Received 6 January 2013
Received in revised form 13 March 2013
Accepted 19 March 2013
Available online 15 May 2013
Keywords:
ß 2013 Jie Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Hypervalent iodine intermediate
Chlorination
Catalytic oxidation
Synthesis
1. Introduction
for catalytic chlorination of aromatic compounds have not been
reported until now. In order to develop a new protocol for
The chemistry of hypervalent iodine organic compounds has
experienced impressive developments since the early 1990s. Due
to their low toxicity, ready availability, easy handling and
reactivity similar to that of heavy metal reagents or anodic
oxidation, hypervalent iodine compounds have received a great
deal of attention [1–5]. They have been extensively used as mild,
highly selective and environmentally friendly reagents in organic
reactions, such as oxidations [6–9], substitutions [10–12], addi-
tions [13–16] and rearrangement reactions [17–19].
Aryl chlorides constitute an important segment of fine and
specialty chemicals, dyes, flame-retardants, pharmaceuticals and
agrochemicals. They also have been extensively used as precursors
in the preparation of various bioactive molecules and pharma-
ceuticals [20–23]. In carbon–carbon bond-forming reactions, such
as Suzuki Miyaura cross-couplings, they play a vital role as
important synthetic intermediates [24–26]. A number of methods
have been used to synthesize aryl chlorides; however, various toxic
catalysts or harmful solvents have been used so far [20,27].
Therefore, less toxic and more environmentally friendly reagents
and solvents in chlorination of aromatic compounds are necessary.
Recently, Zhou and co-worker reported a novel method for
monobromination of electron-rich aromatic compounds using
catalytic hypervalent iodine (III) [28]. However, similar reactions
chlorination of aromatic compounds and extend the scope of
catalytic use of hypervalent iodine reagents in organic synthesis,
we have investigated the chlorination of anisole with m-
chloroperbenzoic acid (mCPBA) as the oxidant and lithium chloride
(LiCl, 1.2 equiv.) as the chlorine source, using a catalytic amount of
iodobenzene (PhI, 0.3 equiv.) as the catalyst in the presence of 4-
methylbenzenesulfonic acid (TsOHÁH2O) in THF at room tempera-
ture for 4 h. The reaction provided the desired product of 4-
chloroanisole with a good yield. Based on successful formation of
the monochlorinated compound, the reaction conditions were
optimized and the results are summarized in Table 1.
2. Experimental
A typical procedure for the catalytic chlorination of electron-rich
aromatic compounds: To THF (4 mL), anisole (0.3 mmol, 32 mg),
TsOHÁH2O (0.3 mmol, 57.1 mg), mCPBA (75%, 0.3 mmol, 69 mg),
PhI (0.12 mmol, 25 mg) and LiCl (0.36 mmol, 16 mg) were added.
The mixture was stirred at r.t. for 24 h. Then H2O (10 mL), sat.aq.
Na2S2O3 (4 mL), and sat. aq. Na2CO3 (4 mL) were added. The
mixture was extracted with CH2Cl2 (3 Â 10 mL) and the combined
organic layer was dried over anhydried Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified on
silica gel plate (hexane/EtOAc = 20/1) to give the yellow oil product
of 4-chloroanisole 35 mg (90%). IR (neat, cmÀ1): 2941, 2868, 1695,
1598, 1503, 1482, 1432, 1297, 1227, 1170, 1097, 1030, 935, 871,
* Corresponding author.
E-mail address: jieyan87@zjut.edu.cn (J. Yan).
1001-8417/$ – see front matter ß 2013 Jie Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.03.049

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T.-T. Li et al. / Chinese Chemical Letters 24 (2013) 535–538
_
Table 1
mCPBA
+
LiCl
+
PhI
Ar-Cl
Optimization of the catalyzed chlorination of anisole. [TD$LINE]
Ar-H
1
TsOH.H2O, THF
2
OMe
OMe
PhI,TsOH.H2O
Scheme 1. The chlorination of aromatic compounds using iodobenzene as catalyst.
+
LiCl
mCPBA
Cl
.
(Table 1, entries 1–6). Oxidants mCPBA, NaBO3Á4H2O, and Oxone
were tested under the same reaction conditions; however, oxone
gave the relatively low yield of 71%, and NaBO3Á4H2O produced
even lower yields (entries 7 and 8). Therefore, mCPBA was chosen
for use in this experiment. Besides LiCl, various kinds of chlorides
such as sodium chloride, potassium chloride and ammonium
chloride were tried as the chlorine source, and LiCl offered the
highest yield among them (entries 3, 9–11). The amount of PhI
was also investigated, and 0.4 equiv. of it was the best choice
(entries 3, 13–16). Without PhI, the product was obtained only in
17% yield (entry 12). 1.0 Equiv. of TsOHÁH2O allowed the
conversion of anisole into the desired product in good yield of
87%; whereas in the absence of it, the yield decreased to less than
16% (entries 15, 17–19). As reported by Zhou, bromination of
aromatic compounds only needed 1 h to complete with
bromides. Considering the differences between chlorine and
bromine, the reaction time was extended to 24 h to complete the
reaction (entry 20).
Having established the optimal reaction conditions for
chlorination of anisole, the scope of chlorination of aromatic
compounds was evaluated for a range of substrates (Scheme 1,
Table 2). It is shown from Table 2 that a variety of electron-rich
aromatic compounds such as aromatic ethers were easily
transformed into the chlorinated products with good yields
(Table 2, entries 1–6), with regioselectivity towards 4-chlori-
nated compounds (entries 1–3). As to other three aromatic
ethers with groups in 4-position, only 2-chlorinated products
were found in moderate yields (entries 8–10). 1,3,5-Trimethyl-
benzene and 1,2,4,5-tetramethylbenzene also gave the corre-
sponding products; however, the yields were relatively low
compared with aromatic ethers (entries 11 and 12). As the
representative with an electron-withdrawing group on an
aromatic ring, chlorobenzene was also tried under the same
Entry Oxidant
(equiv.)
ClÀ
TsOHÁH2O
PhI
Solvent Yield (%)a
(equiv.) (equiv.)
(equiv.)
1
2
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
Oxone
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0
CH3OH
EtOAc
THF
31
80
83
69
78
38
71
39
80
64
29
17
45
53
87
82
16
83
73
90b
3
4
EtOH
MeCN
CH2Cl2
THF
5
6
7
8
NaBO3Á4H2O LiCl
THF
9
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
mCPBA
NaCl
KCl
THF
10
11
12
13
14
15
16
17
18
19
20
THF
NH4Cl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
LiCl
THF
THF
0.1
0.2
0.4
0.5
0.4
0.4
0.4
0.4
THF
THF
THF
THF
THF
1.5
2.0
1.0
THF
THF
THF
a
Isolated yield.
b
Reaction time was 24 h.
799, 695. 1H NMR (500 Hz, CDCl3):
d 7.25 (d, 2H, J = 9.0 Hz), 6.84 (d,
2H, J = 9.0 Hz), 3.80 (s, 3H).
3. Results and discussion
0As shown in Table 1, solvent influenced the reaction greatly
and THF was superior to other solvents with a good yield of 83%
Table 2
The results of the catalytic chlorination of aromatic compounds.
Entry
1
Substrate (1)
Product (2)
Yield (%)a
90
Entry
8
Substrate (1)
Product (2)
Yield (%)b
67
OMe
OMe
Cl
OMe
OMe
[TD$LINE]
[DT$LINE]
[
[TD$LINE]
1a
Cl
2a
OMe
OMe
OMe
OMe
1h
1i
2h
2i
2
3
4
86
88
89
9
10
11
63
58
56
OEt
OEt
Cl
Cl
[TD$LINE]
[DT$LINE]
[DT$LINE]
[DT$LINE]
1b
Me
Cl
Me
2b
OMe
OMe
OMe
OMe
[TD$LINE]
[
[TD$LINE]
[DT$LINE]
1c
Cl
Me
Et
2c
1j
Et
2j
Me
Cl
Cl
OMe
[
[TD$LINE]
[
[TD$LINE]
1k
2k
MeO
OMe
MeO
OMe
OMe
1d
2d

T.-T. Li et al. / Chinese Chemical Letters 24 (2013) 535–538
537
Table 2 (Continued )
Entry
5
Substrate (1)
OMe
Product (2)
Yield (%)a
81
Entry
12
Substrate (1)
Product (2)
Yield (%)b
46
Cl
OMe
Cl
[DT$LINE]
[DT$LINE]
[DT$LINE]
1l
[TD$LINE]
OMe
2l
OMe
2e
1e
6
83
13
86c
OMe
OMe
N
N
Cl
OMe
Cl
[DT$LINE]
[DT$LINE]
[TD$LINE]
[DT$LINE]
MeO
2f
MeO
OMe
1f
1m
Cl
2m
7
PhCl 1 g
2 g
0
a
Isolated yield.
b
c
Determined by GC technique.
Isolate yield when 2 equiv. of LiCl was used.
[(Schme_2)TD$FIG]
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OMe
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