Kaolin-assisted Aromatic Chlorination and Bromination

Article abstract of DOI:10.1039/a804043e

Moist kaolin catalyses the regioselective and high-yielding chlorination and bromination of C₆H₅OR (R = C₁-C₈ alkyl. Bu¹, allyl, cyclohexyl, benzyl) to 4-XC₆H₄OR (X = Cl and Br, respectively) with NaCl0₂ and Mn(acac)₃ in CH₂Cl₂ in the absence and presence of NaBr, respectively, under mild and neutral conditions.

Full text of DOI:10.1039/a804043e

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662 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 662±663$
Kaolin-assisted Aromatic Chlorination and
Bromination$
Masao Hirano,* Hiroyuki Monobe, Shigetaka Yakabe and
Takashi Morimoto
Department of Applied Chemistry, Faculty of Technology, Tokyo University of Agriculture and
Technology, Koganei, Tokyo 184-8588, Japan
Moist kaolin catalyses the regioselective and high-yielding chlorination and bromination of C6H5OR (R ˆ C1±C8 alkyl,
But, allyl, cyclohexyl, benzyl) to 4-XC6H4OR (X ˆ Cl and Br, respectively) with NaClO2 and Mn(acac)3 in CH2Cl2 in the
absence and presence of NaBr, respectively, under mild and neutral conditions.
Use of supported reagents and catalysts for organic
synthesis has gained general acceptance as a new, environ-
mentally benign protocol.1 Aluminosilicate clays are well
characterised by their surface acidities, which render them
ecient, versatile supports or catalysts.1c,2 Somewhat sur-
prisingly, while montmorillonites (bentonites) have achieved
very wide use, kaolin-based reagents or kaolin-assisted reac-
tions appear to be extremely limited.2 We felt from our own
experiments on the oxidation of sul®des to sulfones3a and to
sulfoxides3b that kaolin is slightly inferior as a catalyst to
bentonite. However, a marked catalysis of natural kaolins
has recently been observed upon the protection reaction
of carbonyl compounds4a and the alkylation of benzene.4b
It might therefore be of considerable interest to ®nd further
use of kaolin as a solid catalyst in a variety of organic
reactions.
anisole 4a (4.9%) and o-bromoanisole 5a (1.0%) were
formed. Moreover, Systems A, B have proved to be appli-
cable to gram scale halogenation of 1a with the use of the
same quantity of Mn(acac)3 (0.1 mole % in this case) as
that in the small scale experiment (see Table 1).
An independent experiment with compound 1a carried
out in the absence of moist kaolin brought about no halo-
genation even after a prolonged period (1a recovery 99% by
GLC), clearly indicating that the clay eciently catalyses
the halogenation. Comparative halogenations of 1a using
a common acidic clay, Montmorillonite K10, and a mildly
acidic support, silica gel, in place of kaolin, revealed that
kaolin is superior to the others in its catalytic activity,
selectivity or yield of the product (see Table 1). Another set
of experiments showed that neither NaClO2/NaBr/moist
kaolin nor Mn(acac)3/NaBr/moist kaolin can halogenate 1a,
and also that 2a does not change to 3a under bromination
conditions. Consequently, it could be likely that a positive
chlorine species responsible for the chlorination oxidises
‡
bromide ion quickly to generate an electrophilic Br species.
Scheme 1
We chose the electrophilic halogenation5 of aromatic
ethers as a target, since certain alkyl 4-halogenophenyl
ethers exhibit bioactivity and are useful intermediates en
route to many ®ne chemicals; for example, 4-chlorophenyl
octyl ether 2h is a very active plant growth regulator.6 Thus,
treatment of anisole 1a with a combination of sodium
chlorite (NaClO2) and a catalytic amount of Mn(acac)3
(1 mole % with respect to 1a)7 in CH2Cl2 at 25 8C in the
presence of kaolin preloaded with a small amount of
water (moist kaolin)% a€orded monochloroanisoles with
high selectivity to p-isomer 2a (System A in Scheme 1).
System A can successfully be used for the selective chlorin-
ation of a series of alkyl phenyl ethers 1b±1k, irrespective of
chain length or steric bulk of the alkyl groups. During this
study, we have fortunately found that nuclear bromination
is readily achieved by simple addition of NaBr to System A
(System B), giving good to quantitative yield of alkyl
p-bromophenyl ethers 3a±3k, along with minor amounts of
p-chloro derivatives 2 (<4%). GLC analyses of reaction
mixtures showed that Systems A, B achieved 100% regio-
speci®city, except for halogenations of 1a where o-chloro-
Scheme 2
The kaolin-based biphasic systems favorably aided the
regiospeci®c halogenation of multisubstituted benzenes 6±10
(Scheme 2). Although highly activated arenes such as
veratrole 8 and pyrogallol trimethyl ether 10 are vulnerable
to polyhalogenations,8 the present procedures can be con-
trolled to stop at the monohalogenation stage. Like
halogenations of simple alkyl phenyl ethers, the tendency
that hydrogens attached to the more nucleophilic carbon
atoms on the benzene rings5a are preferentially displaced by
chlorine and bromine is quite general.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
%The e€ect of water on surface-mediated reactions has been
described elsewhere.7

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J. CHEM. RESEARCH (S), 1998 663
Table 1 Aromatic mono-chlorination and -bromination of aromatic ethersa
Chlorination
Bromination
Ether
NaClO2 (mmol)
t/min
Product (%)b
NaClO2 (mmol)
NaBr (mmol)
t/min
Product (%)b
1a
1ac
1ae
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
6
7
8
1.7
2.1
2.1
14h
1.5
1.6
1.7
1.5
1.6
1.6
1.5
1.5
1.9
2.2
1.5
2.0
1.5
1.2
1.3
100
60
60
50
60
80
100
70
80
100
70
60
60
120
110
70
2a (94), 4a (4.9)
2a (67), 4a (7.5)d
2a (72), 4a (13)f
2a (94)
2b (96)
2c (98)
2d (quant.)
2e (93)
2f (99)
2g (quant.)
2h (99)
2i (96)
2j (99)
2k (60)i
11a (93)
12a (96)
13a (94)
1.2
1.4
1.4
12h
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.5
1.0
1.3
1.0
1.1
1.0
3.0
3.0
3.0
30
110
60
3a (98), 5a (1.0)
3a (99)
120
130
100
160
100
140
130
110
90
90
80
150
120
60
3a (90)g
3a (95)
3b (95)
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
4.0
4.5
4.5
4.5
3.5
4.5
3.5
3c (97)
3d (96)
3e (92)
3f (97)
3g (97)
3h (95)
3i (98)
3j (98)
3k (66)j
11b (95)
12b (quant.)
13b (quant.)
14b (92)
15b (97)
60
80
80
120
90
120
9
10
14a (95)
15a (98)
aAt 25 8C; 1 mmol ether, 0.01 mmol Mn(acac)3, 1 g moist kaolin, 10 ml CH2Cl2. bYield of chromatographically purified product based on
f
the starting ether. cMoist montmorillonite K10 used as support. dca. 20% of 1a remained. eSilica gel as support. ca. 13% (GLC area
ratio) of a unknown product was formed. gca. 3% of 2a was formed. hAt 30 8C; 10 mmol 1a, 0.01 mmol Mn(acac)3, 3 g moist kaolin,
30 ml CH2Cl2. GLC yield. GLC yield; 2.4% of 1k remained.
i
j
bromination product. Halogenoethers thus obtained were fully
characterised by MS and NMR spectroscopies.
Surface-mediated reactions a€ord excellent product
yield and selectivity often unattainable by solution phase
counterparts.9 For fascinating instances, CuCl2/alumina
(100 8C, 2±3 h),9b ButOCl/zeolite (25 8C, 1 h±2 weeks),9c
and Br2/zeolite (ambient, 1±5 h)9d systems have elegantly
achieved high-yielding, regio-controlled nuclear chlorina-
tion9b,c and bromination9d of a number of arenes. Simple,
inexpensive procedures demonstrated here accomplish e-
cient halogenations under mild conditions and their regio-
speci®cities are impressive. In addition, NaBr is more
attractive as the bromine source than Br2. They could
therefore be added to a list of synthetically useful halogena-
tion methodologies.9 In view of the easy accessibility and
excellent reaction performance of the new biphasic system,
we are now looking for another synthetic target to make use
of the remarkable catalysis by kaolin.
Received, 29th May 1998; Accepted, 30th June 1998
Paper E/8/04043E
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Experimental
Sodium chlorite (available chlorine ca. 82% by iodometry),
Mn(acac)3, and substrates 1a, b, d, j, k, 6±10 were used as received
from commercial sources. Ethers 1c, 1e±1h10 and 1i11 were prepared
by known methods. Moist kaolin (H2O content, 13 wt. %) was
prepared by adding deionised water (0.15 g) in portions to commer-
cial kaolin (Kukita; 1.0 g), followed by vigorous shaking of the
mixture after every addition for a few minutes until a free-¯owing
powder was obtained. Montmorillonite K10 (Aldrich) and predried
silica gel (Merck silica gel 60) were treated with deionised water
as above.
Chlorination Procedure.ÐA representative procedure was as
follows. A 30 ml, two-necked, round bottom ¯ask, equipped with a
Te¯on-coated stirrer bar and re¯ux condenser, was charged with
anisole 1a (1 mmol), freshly prepared moist kaolin (1 g), Mn(acac)3
(0.01 mmol) and dried (molecular sieves) CH2Cl2 (10 ml), and the
mixture stirred for a few minutes. Sodium chlorite (1.7 mmol as
available chlorine) was then added in one portion with stirring.
The cloudy suspension was kept at 25 8C while ecient stirring was
continued in order to ensure smooth reaction and to attain re-
producible results. After 100 min (agitation periods after complete
addition of NaClO2 are indicated in Table 1) the whole material
was transferred to a sintered glass funnel and the ®lter cake washed
thoroughly with portions of dry diethyl ether (ca. 100 ml). Rotary
evaporation of the solvent, followed by chromatography on
a silica gel column (Merck silica gel 60, hexane±AcOEt), gave
p-chloroanisole 2a in 94% yield.
Bromination Procedure.ÐThe bromination was carried out by
adding NaClO2 and NaBr both in one portion to a stirred mixture
of ether, Mn(acac)3, and moist kaolin CH2Cl2. After a given time,
work-up and chromatographic isolation as above gave the pure
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