Note: Descriptions are shown in the official language in which they were submitted.
1~845S
PROCESS FOR ~EHYDROHALOGENATING (POLYHALOALI~YL)BENZENES
This invention relates to processes for pre-
paring (haloalkenyl)benzenes including (polyhaloalkenyl)-
S benzenes.
~ Haloalkyl)styrenes are useful as para~
siticides and insecticides. They are also useful
intermediates in the manufacture of other biologically
active compounds. Such compounds are conventionally
prepared by reacting a halogenated organic compound
with an a-methylstyrene in the presence of a free-
-radical initiator which usually comprises an organic
amine and a copper-containing material. These known
methods for preparing haloalkenylber.z2nes require
long reaction times and undesirably high reaction
temperatures and give somewhat low yields of product.
In accordance with the present invention,
(haloalkenyl)benzenes and other (haloalkenyl)arenes are
advantageously obtained by a dehydrohalogenation process,
which comprises contacting a (polyhaloalkyl)arene in
which polyhaloalkyl has a benzylic halogen and at least
26,16~-~
~L
ll~B4S5
one non-benzylic aliphatic halogen with a catalytic
amount of a halide of titanium which has been treated
with water and is in neat form or a halide of antimony
in neat form in the liquid phase at temperatures below
100C. Surprisingly, the benzylic halogen of the poly-
haloalkyl group is selectively eliminated to form the
desired (haloalkenyl)arene while the non-benzylic
aliphatic halogen(s) are left undisturbe~. The ~haio-
alkenyl)benzenes produced in the practice of this
invention are useful as biologically active compounds
as described hereinbefore and as intermediates in the
preparation of other biologically active compounds.
By a (polyhaloalkyl)arene is meant an aromatic
compound in which an aromatic ring bears at least one
polyhaloalkyl substituent. In the polyhaloalkyl substi-
tuent, one halogen is bonded to the alkyl carbon bonded
to the aromatic ring (hereinafter called a benzylic
halogen) and at least one halogen is bonded to one other
alkyl carbon (hereinafter called a non-benzylic halogen).
By "arene" is meant an aromatic compound having one or
more aromatic rings such as benzene, naphthalene,
anthracene as well as substituted arenes. The substi-
tuents include halo, nitro, alkyl, alkoxy, alkylthio,
axyl, aryloxy, sulfo, carboxy, carboxylate ester, --
haloalkyl including polyhaloalkyl, haloaryl and other
substituent groups that do not interfere with dehydro-
halogenation reactions that are catalyzed by Lewis
acids. Such substituents are inert in the dehydro-
halogenation reactions.
. Preferred (polyhaloalkyl)arenes are repre-
sented by Formula I:
26,164-F -2-
111~34~i;~ii
--3--
CH3-C~Y
Ar
(R)n
wherein Ar is arene, preferably benzene, each R is indi-
vidually halo, alkyl, haloalkyl .ncluding pol~haloa'X-Yl
Y .
such as -CX3 (e.g., -CF3) and CH3-C-X wherein X and Y
are as defined herein, aryl, haloaryl, nitro, alkoxy,
and other inert monovalent organic radicals, X is halo,
Y is haloalkyl or substituted haloalkyl wherein alkyl
has from 2 to 3 carbons and the non-halogen substituent
or substituents may be, for example, nitro or alkoxy,
and n is 0 to the maximum number of remaining available
ring positions on Ar. Preferably n is from 0 to 2 when
Ar is benzene. More preferably, each ~ is individually
halo such as Cl, Br, or F; alkyl having 1 to 4 carbons
such as -CH3; alkoxy such as -OCH3 and others having
1 to 4 carbons; and -NO2. Most preferably each R is
individually Cl, Br or -N02. X is more preferably Cl
or Br, most preferably Cl. Y is more preferably halo-
alkyl represented by the formula:
-CH2-C-R '
R'
wherein X' is Cl or Br, each R' is individually H,
halo such as Cl, Br or F, lower alkyl or -NO2. Most
preferably Y is -CH2CCl2R' wherein R' is H, Cl, Br,
26,164-F -3-
3455
--4--
-CH3 or -C2H5. For example, Y is most preferably
-CH2CC13, -CH2CCl2Br, -CH2CHCl2 and -CH2CH2Cl.
Examples of especially preferred poly(halo-
alkyl)arenes include 1,3-dichloro-5-(1,3,3,3-tetra-
chloro-1-methylpropyl)benzene, 1,3-dichloro-5-(1,3,3-
-trichloro-1-methylpropyl)benzene and similar 1,3-
-dihalo-5-~polyhalobutyl)benzenes. vther prefei-L-ed
(polyhaloalkyl)arenes include 3-chloro-1-(1,3,3,3-
-tetrachloro-l-methylpxopyl)benzene and similar
3-halo-1-(polyhalobutyl)benzenes.
(Polyhaloalkyl)arenes may be prepared by
known methods. For example, ~methylstyrene or ar-
-substituted methylstyrene is reacted with a poly-
haloalkane such as carbon tetrachloride, bromotri-
chloromethane, methylene chloride or dichloroni-
tromethane in the presence of an amine and cuprous
chloride to produce a desired (polyhaloalkyl)benzene.
Lewis acids which are suitably employed in
the practice of this invention are the Lewis acids
which catalyze the elimination of the benzylic halogen
from the (polyhaloalkyl)arene via a dehydrohalogenation
reaction while essentially all of the non-benzylic halo- -
gen substituent(s) of the (polyhaloalkyl)arene remain
bonded to the (polyhaloalkyl)arene. Such Lewis acids
are stated herein to be suitably active if, during the
preferential dehydrohalogenation of essentially all
(>95 mole percent) of benzylic halogen of the (poly-
haloalkyl)arene, less than lO, preferably less than 5,
mole percent of non-benzylic halogen is eliminated.
26,164-F -4-
~1184~;5
--5--
Examples of Lewis acids which, in neat
(undiluted) form, are suitably active include (1) the
halides of titanium, preferably TiC14, which have been
treated with water and (2) the halides of antimony,
preferably antimony pentachloride. of the neat forms,
the titanium tetrahalides which have been treated with
from 0.1 to 2 moles of water per mole of the titanium
tetrahalide are more preferred, with Ti~14 beir,g treated
from 0.25 to 1.75 moles of water per mole of TiC14 being
most preferred.
In the practice of this invention, the
(polyhaloalkyl)arene is contacted with a catalytic
amount of a suitably active Lewis acid under dehy-
drohalogenation conditions. A catalytic amount is
any amount of suitably active Lewis acid which
catalyzes the selective dehyd~ohalogenation of the
(polyhaloalkyl)arene such that substantially all of
the benzylic halogen thereof is eliminated. Advan-
tageously, such catalytic amounts are within the
range from 0.1 to 20 weight percent of suitably
active Lewis acid based on the weight of (polyhalo-
alkyl)arene, preferably from 0.1 to 10 weight percent
of the Lewis acid, most preferably from 0.2 to 3
weight percent of the Lewis acid.
In addition to the aforementioned starting
ingredients, a solvent such as carbon tetrachloride,
ethylene dichloride or similar halohydrocarbons is
optionally employed. When used, the solvent is present
in an amount between 0.5 and 3 liters of solvent per
mole of the (polyhaloalkyl)arene.
26,164 F -5-
- ~118A~5
--6--
While the temperature of the dehydrohalo-
genation reaction is not particularly critical, the
reaction is advantageously conducted in the liquid
phase at a temperature below 100C, preferably between
25C and 80C, and most preferably between 55C and
80C. Preferably, the suitably active Lewis acid
catalyst is added to a stirred mixture of the (poly-
haloalkyl)arene and the optior.al solvent. It is
sometimes desirable to add the (polyhaloalkyl)arene
diluted with solvent to a stirred solution of the
catalyst in solvent. Thus, the rate of hydrogen
halide evolution is controlled by the slow addition
of reactant.
After the (polyhaloalkyl)arene is contacted
with catalyst, the reac~ion begins immediately, as
evidenced by evolution of hydrogen halide gas. The
reaction is allowed to proceed to completion while
agitating the reaction mixture sufficiently to keep
the catalyst in suspension. The reaction pressure
is not critical and is conveniently atmospheric.
The product of the dehydrohalogenation
reaction is primarily a (polyhaloalkenyl~arene
wherein the benzylic halogen and hydrogen on an
adjacent carbon are eliminated. In embodiments of
particular interest, the (polyhaloalkenyl)arene is
represented by formula II:
CH2=C-Y
Ar II
( R) n
26,164-F -6-
P~
111~345~i
--7--
wherein R, Y and n are ~s defined hereinbefore. In
preferred embodiments of this invention, the dehydro-
halogenation is sufficiently selective such that more
than 95 mole percent of benzylic halogen is eliminated,
most preferably more than 99 mole percent, and less
than 5 mole percent of non-benzylic halogen is elimi-
nated most preferably less than 2 mole percent.
The following examples are given to further
illustrate the invention. All percentages in the
examples are by weight unless otherwise indicated.
Example 1
Preparation of 3,5-dlchloro-~-methylstyrene
Chlorine gas is bubbled through 129 g of
3,5-dichlorotoluene in the presence o~ light until
no further adsorption occurs. An increase in weight
of 83 g results. To the product, weighing 212 g,
is added dropwise 400 g of 8 percent fuming sulfuric
acid. After being stirred for 30 hours the mixture
is poured over cracked ice. The 3,5-dichlorobenzoic
acid which precipitated is washed well with water
and dried. It weighs 145 g, or 95 percent yield
based on the dichlorotoluene. The acid is converted
to 3,5-dichlorobenzoyl chloride in 95 percent yield
by treating with 125 g thionyl chloride. The chloride,
weighing 151 g, is then allowed to react with 150 ml
of methyl alcohol and the resulting methyl 3,5-di-
-chlorobenzoate, which when distilled at 120C-125C
at 7 mm weighs 133 g, or 90 percent of theory. The
ester is treated with 2 equivalents of methyl magnesium
chloride (125 g), the Grignard complex hydrolyzed, and
the product then dehydrated by refluxing with NaHSO4.
26,164-F -7-
.
4 ~ 5
The 3,5-dichloro-~-methylstyrene obtained weighs 88 g,
or 72 percent of theory based on the ester used, and
boiled at 109C-111C at 12 mm. Its specific gravity
is 1.196 and its refractive index is 1.5660, both
measured at 25C.
Addition of CC14
The 3,5-dichloro-~-methylstyrene is placed
in a 250 ml vessel equipped with stirring means and a
heating means. A mixture including 18.7 g (0.1 mole)
of 3,5-dichloro-~-methylstyrene, as well as 46.2 g
(0.3 mole) of CC14 and 0.4 g of cuprous chloride is
formed with stirring. To the mixture is added 1.6 g
(0.016 mole) of cyclohexylamine. The mixture is
heated to the reflux temperature of CC14 and main-
tained at reflux temperature until completion of
the reaction in 30 minutes. The reaction mixture
is cooled and filtered, and the solvent is removed
under vacuum leaving 31.2 g (91.5 percent yield) of
residual product. This residue is recrystallized
from hexane to yield essentially pure 1,3-dichloro-
-5-(1,3,3,3-tetrachloro-1-methylpropyl)benzene
exhibiting a melting point of 44.5-46.5C.
Dehvdrohaloqenation with SbC15 -
A mixture composed of a 137 g (0.40 mole)
portion of the 1,3-dichloro-5-(1,3,3,3-tetrachloro-
-l-methylpropyl)benzene (DCTCB) obtained above and
250 ml of CC14 is formed in a 500 ml flask equipped
with a stirring and a heating means. With stirring,
a 7 g portion (0.023 mole) of SbC15 is added to the
flask and dehydrochlorination (as evidenced by HCl
gas) to form a crude product mixture occurs at room
26,164-F -8-
455
g
temperature. The crude product mixture is heated
to reflux (82~C), is held at this temperature for
30 minutes, and is then allowed to cool to a tem-
perature near ambient. To the crude product mixture
a 150-ml portion of CCl4 is added and then a 200-ml
portion of 3N HCl is added with stirring. An aqueous
and an organic layer are formed. The organic and
a~ueous layers are separated and 200 ml of water is
added to the organic layer with stirring. The organic
layer is stirred over Na2S04 to remo~e any water
remaining. The carbon tetrachloride present in the
organic layer is removed under a vacuum leaving 115.8 g
of a crude product. Distillation of the crude product
yields 100.2 g (0.33 mole) of product containing at
least 95 percent of 3,5-dichloro-~-(2,2,2-trichloro-
ethyl)styrene (DCTCS) represented by the structure:
H2C=C-CH2-CCl3
Cl ~ Cl
and less than 5 percent of diene represented by the
structure:
H2C=C-CH=CC12
I
Cl ~ Cl
Example 2
Dehydrohaloqenation with H20 Treated TiCl4
A mixture consisting of 5 g (0.0147 mole)
of the DCTCB produced according to Example 1, 50 ml
of CCl4 and 0.020 ml of water is placed in a 100 ml
26,164-F -9-
--10--
flask. The mixture is heated to reflux (about 90C)
and 0.173 g (0.000911 mole) of TiC14 is added to the
mixture. Evolution of HCl is noted as the reflux
continues for 2 hours. The mixture is cooled to
45C and 25 ml of concentrated hydrochloric acid is
added. An organic layer and an aqueous layer are
formed and separated. The organic layer is washed
with wateî. The solvent is then removed from the
organic layer in vacuum. The remaining residue
which weighs 4.0~ g ~0.0133 mole) for a 91 percent
yield is identified as DCTCS as prepared in Example 1.
Analysis by gas-liquid chromatography (GLC) shows
the residue to contain 97.5 percent of the afore-
mentioned styrene (DCTCS) and less than 2.5 percent
of the diene.
26,164-F -10-
S5
--11--
1. A process for the dehydrohalogenation
of a (polyhaloalkyl)arene wherein in the polyhaloalkyl
one halogen is a benzylic halogen and at least one
halogen is a non-ben~ylic halogen characterized by
contacting the (polyhaloalkyl)arene with a catalytic
amount of a halide of titanium which has been treated
with water and is in neat form or a halide of antimony
in neat form in the li~uid phase at temperatures below
100C to form a (haloalkenyl)arene.
2. Process of Claim 1 characterized in
that the (polyhaloalkyl)arene employed is represented
by the formula:
CH3-C-Y
Ar
(R)n
wherein Ar is arene, each R is individually halo,
nitro or an inert monovalent, organic radical, X is
halo, Y is haloalkyl or substituted haloalkyl wherein
alkyl has 2 or 3 carbons and the non-halogen substi-
tuent or substituents are nitro or alkoxy; and n is 0
26,164-F
