Highly efficient, para-selective oxychlorination of aromatic compounds using potassium chloride and Oxone

Article abstract of DOI:10.1081/SCC-120002013

A highly efficient, regioselective method for oxychlorination of aromatic compounds is possible through electrophilic substitution of chlorine generated in situ from KCl as a chlorine source and Oxone as an oxidant for the first time.

Full text of DOI:10.1081/SCC-120002013

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HIGHLY EFFICIENT, PARA-SELECTIVE
OXYCHLORINATION OF AROMATIC COMPOUNDS USING
POTASSIUM CHLORIDE AND OXONE®*
N. Narender a , P. Srinivasu a , S. J. Kulkarni b & K. V. Raghavan a
a Catalysis Group , Indian Institute of Chemical Technology , Hyderabad, 500 007, India
b Catalysis Group , Indian Institute of Chemical Technology , Hyderabad, 500 007, India
Published online: 16 Aug 2006.
To cite this article: N. Narender , P. Srinivasu , S. J. Kulkarni & K. V. Raghavan (2002) HIGHLY EFFICIENT, PARA-SELECTIVE
OXYCHLORINATION OF AROMATIC COMPOUNDS USING POTASSIUM CHLORIDE AND OXONE®*, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:2, 279-286, DOI: 10.1081/
SCC-120002013
To link to this article: http://dx.doi.org/10.1081/SCC-120002013
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SYNTHETIC COMMUNICATIONS, 32(2), 279–286 (2002)
HIGHLY EFFICIENT, PARA-SELECTIVE
OXYCHLORINATION OF AROMATIC
COMPOUNDS USING POTASSIUM
CHLORIDE AND OXONEÕ
*
N. Narender, P. Srinivasu, S. J. Kulkarni,y
and K. V. Raghavan
Catalysis Group, Indian Institute of
Chemical Technology, Hyderabad 500 007, India
ABSTRACT
A highly efficient, regioselective method for oxychlorination
of aromatic compounds is possible through electrophilic sub-
stitution of chlorine generated in situ from KCl as a chlorine
source and OxoneÕ as an oxidant for the first time.
Chlorinated aromatic compounds have a wide diversity of uses. They
can serve as precursors for numerous functionalities, such as phenols aro-
matic ethers and thioethers, amines, arylhydrazines, benzonitriles, fluoro-
aromatic, silylated aromatics and aromatic hydrocarbons.1 The chlorination
of aromatic compounds has been extensively described using many
reagents,2 such as molecular chlorine,3 sulfuryl chloride,4 alkyl and acyl
*IICT Communication No. 4580.
yCorresponding author. Fax: 0091-40-7173387/7173757; E-mail: sjkulkarni@
iict.ap.nic.in
279
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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NARENDER ET AL.
hypochlorites,5 inorganic chlorides,6 KCl/m-CPBA/18-crown-6,7 KCl/
NaBO3/Na2WO4,8 KCl/H2O2/NH4VO3,9 N-chloro-succinimide,10 benzyl-
trimethyl ammonium tetrachloroiodate (BTMAICl4),11 dichlorinemonoxide
(Cl2O),12 PhICl2 in trifluoroacetic acid13 and N-chloroamines,14 -amides and
-sulfonamides.15 The methods reported have some limitations such as use of
strong and non-selective chlorinating agents, toxic and expensive reagents,
low yields and long reaction times.
Industrial synthesis of chloroarenes are commonly performed with
molecular chlorine in the presence of Lewis or mineral acids at 20–80ꢀC.16
Catalysts such as aluminium(III), iron(III), tin(IV) or zinc(II) chlorides, to
name just a few, have been used widely.17 The major disadvantages are
poor regioselectivities, corrosion caused by the highly reactive species and
hydrogen chloride side product and disposal problems. Thus, a great deal of
efforts are being directed toward carrying out the chlorination of arenes in
the gas and liquid phases using alumino-silicate catalysts, especially zeolites,
in order to achieve better selectivities under milder conditions.18 Irreversible
damage caused to the zeolites by hydrogen chloride is, however, a stumbling
block, so that industrial applications are still rare. To overcome these diffi-
culties some researchers have utilized a combination of hydrochloric acid
and suitable oxidant19 such as tert-butyl hydroperoxide, hydrogen peroxide
or m-chloroperbenzoic acid, which in situ generates positive chlorine species
for the chlorination of aromatic substrates.
In this communication we report a new method for the para selective
(regioselective) oxychlorination of aromatic compounds using commercially
available OxoneÕ as an oxidant and KCl as a chlorine source. We observed
smooth chlorinations in acetonitrile without any additional catalyst.
Scheme 1.
A number of different aromatic substrates were subjected to
the chlorination reaction to test the generality of this method and the
results are summarized in Table 1. These reactions proceeded efficiently
under mild conditions in acetonitrile with high yields and regio-
selectivity with KCl and OxoneÕ. Potassium peroxymonosulfate is an
inexpensive and readily accessible oxidizing agent. It is commonly used as

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281
Table 1. Regioselective Oxychlorination of Aromatic Compounds
with KCl and OxoneÕ in Acetonitrilea

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NARENDER ET AL.
OxoneÕ (2KHSO5ꢁKHSO4ꢁK2SO4) and is a versatile oxidant for the trans-
formation of a wide range of functional groups.20 The results shown in Table 1
indicate that the reaction is successful for a variety of aromatic compounds.
Introduction of an electron-withdrawing group on the aromatic ring
substantially decreases the rate of ring chlorination (Table 1, Entries 7 and 10)
while on electron donating group increases it. As is evident from the Table 1
aromatic substrates of greater, moderate reactivity ex. methoxy, hydroxy
and alkyl benzenes react readily with KCl/OxoneÕ to give essentially
quantitative yields of the monochloro derivatives with high para selectivity
with little or no tendency to polychlorination. Less reactive substrates such
as nitrobenzene, chlorobenzene, benzoic acid could not be chlorinated even
at elevated temperature (80ꢀC). In the case of 2-nitrophenol the corres-
ponding monochloro phenol (4-chloro-2-nitrophenol) was obtained in
moderate yields.
The results show that chlorination of toluene (Table 2, Entry 4) with
two fold excess of KCl and OxoneÕ afforded (mono) 2 and 4-chlorotoluene
in 97% yield and a small amount (3%) of 2,4-dichlorotoluene, whereas
anisole, phenol and acetanilide (Table 2, Entries 1–3) furnished dichlo-
rinated compounds as a major products along with a small amount of
monochlorinated compounds. The interesting difference between highly
activated aromatics gives the dichlorinated compounds whereas moderately
activated aromatics gives the monochlorinated compounds. Then, we can
selectively prepare the desired chloro-substituted compound by using
calculated amount of KCl and OxoneÕ in case of highly activated aromatics.
A wide range of solvents has been employed in these reactions (Table 3),
including carbon tetrachloride, hexane, dichloromethane, methanol and
acetonitrile. However, the yields, rates of reaction and degree of para-
selectivity generally appeared to be optimum in acetonitrile.
Table 2. Oxychlorination of Aromatic Compounds with 2.2 Equiv. of KCl and
OxoneÕ in Acetonitrilea
Yield (%)b
Time
(h)
Conversion
(%)
Substrate
Para
Ortho
Di
Others
1. Anisole
2. Phenol
3. Acetanilide
4. Toluene
15
15
15
24
100
100
100
100
12
20
–
–
2
12
29
81
78
61
3
7
–
27
–
68
aSubstrate (2 mmol), KCl (4.4 mmol), OxoneÕ (4.4 mmol), CH3CN (10 ml), r.t.
bThe products were characterised by NMR, Mass, GC analysis.

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283
Table 3. The Effect of Solvent on the Oxychlorination of Anisole Using KCl-
OxoneÕ Systema
Yield (%)b
Time
(h)
Conversion
(%)
Solvent
Para
Ortho
Di
1. Acetonitrile
2. Methanol
3. Dichloromethane
4. Carbon tetrachloride
5. Hexane
15
15
15
15
15
98
97
5
–
–
90
72
5
–
–
8
24
–
–
–
–
1
–
–
–
aAnisole (2 mmol), KCl (2.2 mmol), OxoneÕ (2.2 mmol), Solvent (10 ml), r.t.
bThe products were characterised by NMR, Mass, GC analysis.
Two experimental parameters deserve emphasis. First, the nature of
the solvent has a dramatic influence on the regioselectivity. Switching from
the non-polar carbon tetrachloride (polarity ¼ 0.0D) to the strongly polar
acetonitrile (polarity ¼ 3.92D) results in a change of yields from 0 to 98%
for anisole chlorination. Even greater paraselectivity ( para/ortho upto 90/8)
was obtained by using acetonitrile as a solvent compared to methanol.
Secondly, the nature of oxidant used has a dramatic influence on the
yields and selectivity. We surveyed the oxychlorination with various
oxidants. Reactions were conducted with anisole as a probe-substrate at
room temperature in acetonitrile. However, OxoneÕ is far superior to the
other oxidants for example, H2O2 give little of the product and TBHP and
molecular O2 showed no sign of reaction after 15 h. The best oxidant is
OxoneÕ from the standpoint of highest yield and selectivity.
The reaction proceeds efficiently in high yields at ambient temperature
and pressure. The role of OxoneÕ was confirmed by conducting a blank
experiment, where the formation of chloro compound was not observed.
ArH þ KCl þ 2KHSO5 ꢁ KHSO4 ꢁ K2SO4
! ArCl þ KOH þ K2S2O8 ꢁ KHSO4 ꢁ K2SO4 þ H2O
ð1Þ
2KHSO5 ꢁ KHSO4 ꢁ K2SO4 þ KCl
! KOH þ HOCl þ K2S2O8 ꢁ KHSO4 ꢁ K2SO4
ð2Þ
ð3Þ
2HOOSO3K ! 2HOꢁ þ 2ꢁOSO3K
KCl þ 2HOꢁ þ 2ꢁOSO3K ! KOH þ HOCl þ K2S2O8
ð4Þ
ð5Þ
ArH þ HOCl ! ArCl þ H2O

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NARENDER ET AL.
A typical oxychlorination of an aromatic compound in the presence of
OxoneÕ proceeds according to the stoichiometry of Equation 1. It is
believed that the chlorination proceeds via the formation of hypochlorous
acid. The hypochlorous acid has higher instability due to pronounced ionic
nature and thus more reactivity towards the aromatic nucleus. The absence
of chlorination of the ring methyl group (Table 1, Entries 9–13) is indicative
of the electrophilic mechanism of the reaction rather than a radical pathway.
Furthermore, chlorination of alkylbenzenes gives large amounts of benzyl
chlorides as side products,21 such drawbacks could be avoided using this
system.
In conclusion, we have developed a novel system for the regioselective
oxychlorination of aromatic compounds by using KCl and OxoneÕ in aceto-
nitrile under ambient conditions. The results reported here demonstrate that
reagent system possess considerable practical advantages over traditional
reagents for electrophilic chlorination reactions. The commercial availability
of the reagents and reactions are clean, high yielding and work-up is simple.
The absence of side chain chlorination products in reaction conducted in
acetonitrile suggests a substantial increase in the rate of the ionic process.
We are currently extending this methodology to other halogenation
reactions.
General Procedure for the Chlorination of Aromatic Compounds:
OxoneÕ (2.2 mmol) was added to a well stirred solution of KCl
(2.2 mmol) and substrate (2 mmol) in acetonitrile (10 ml) and the reaction
mixture was allowed to stir at room temperature. The reaction was moni-
tered by thin layer chromatography (TLC). After the completion of the
reaction, the mixture was filtered and solvent evaporated under reduced
pressure. The products were purified by column chromatography over
1
silica gel and confirmed by H NMR and Mass spectra.
ACKNOWLEDGMENTS
We are thankful to Department of Science & Technology, New Delhi
for funding, DST project No.: SP/S1/H07/97.
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Received in the UK November 20, 2000

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