SPECIFICATION
PROCESS FOR PREPARING 4-HALOCATECHOL COMPOUND
TECHNICAL FIELD
[0001]
The present invention relates to a novel process for
preparing a 4-halocatechol compound. The 4-halocatechol
compound is a compound useful as a starting material or a
synthetic intermediate for a medicine, an agricultural chemical, etc.
The present invention also relates to high purity 4-
chloromethylenedioxybenzene and a process for preparing the
same. The high purity 4-chloromethylenedioxybenzene is a
compound useful as a starting material or a synthetic
intermediate for a medicine, an agricultural chemical, etc.
BACKGROUND ART
[0002]
Heretofore, as a process for preparing a 4-halocate-
chol compound such as 4-chloromethylenedioxybenzene, etc.
from a catechol compound, there are disclosed, for example,
the following methods.
(1) A method of producing 5-chloro-l,3-benzodioxol by
reacting benzodioxol, aluminum trichloride and diphenyl
sulfide in' the presence of sulfuryl chloride (for example,
see Patent literature 1).
(2) A method of producing l-chloro-3,4-methylenedioxy-
benzene by reacting 1,2-methylenedioxybenzene and acetyl
chloride in-acetonitrile in the presence of eerie ammonium
nitrate (for example, see Non-patent literature 1).
(3) A method of producing 1-chloro or bromo-3,4-methylene-
dioxybenzene by reacting methylenedioxybenzene and N-chloro
or bromosuccinimide in an ionic liquid solvent (for
example, see Non-patent literature 2).
However, according to these methods, the reaction

systems are complicated, and yet, there are problems that a
gas having potent toxicity and corrosiveness such as
chlorine gas, hydrogen chloride gas, sulfur dioxide, etc.
occurs, or the post-treatment of the reaction mixture is
complicated, and the like, so that they are disadvantageous
as an industrial preparation process of a 4-halocatechol
compound.
Also, it is needless to say that a high purity 4-
chloromethylenedioxybenzene which does not substantially
contain impurities such as methylenedioxybenzene which is a
remaining starting material and 4,5-dichloromethylenedioxy-
benzene which is a by-product, etc. is useful for using it
as a starting material or a synthetic intermediate for a
medicine, an agricultural chemical, etc. However, in
either of the references, there was no description about a
purity of the resulting 4-chloromethylenedioxybenzene.
Patent literature 1: WO 02/16352 Al
Non-patent literature 1: Synlett, 221 (2003)
Non-patent literature 2: Adv. Synth. Catal., 346, 77 (2004)
DISCLOSURE OF THE INVENTION
PROBLEMS TO BE SOLVED BY THE INVENTION
[0003]
An object of the present invention is to solve the
above-mentioned problems and to provide an industrially
suitable process for preparing a 4-halocatechol compound,
which is capable of preparing the 4-halocatechol compound
under mild conditions by a simple and easy method with high
yield.
Another object of the present invention is to provide,
high purity 4-chloromethylenedioxybenzene which is optimum
for using it as a starting material or a synthetic inter-
mediate for a medicine, an agricultural chemical, etc., and
does not substantially contain methylenedioxybenzene which
is a remaining starting material and 4,5-dichloromethylene-

dioxybenzene which is a by-product, and a process for
preparing the same.
MEANS TO SOLVE THE PROBLEMS
[0004]
The present invention relates to a process for
preparing a 4-halocatechol compound represented by the
formula (3):
[0005]

[0006]
wherein R1 and R2 may be the same or-different from
each other and each represent a hydrocarbon group,
R3 , R4 and R5 each represents groups which do not
participate in the reaction, R1 and R2 may be bonded,
to each other to form a ring, and X represents a
halogen atom,
which comprises reacting a catechol compound represented by
the formula (1):
[0007]

[0008]
wherein R1 , R2 , R3 , R4 and R5 have the same meanings
as defined above,
with a 1,3-dihalo-5,5-dimethylhydantoin represented by the
formula (2) :
[0009]


[0010]
wherein X has the same meaning as defined above.
The present invention also relates to high purity 4-
chloromethylenedioxybenzene which has a methylenedioxy-
benzene content of 0.5% by weight or less and a 4,5-di-
chloromethylenedioxybenzene content of 0.5% by weight or
less.
The present invention further relates to a process
for preparing the high purity 4-chloromethylenedioxybenzene
which comprises reacting methylenedioxybenzene with a
chlorinating agent and then subjecting to distillation and
purification to obtain the high purity 4-chloromethylene-
dioxybenzene .
EFFECTS OF THE INVENTION
[0011]
According to the present invention, it can be
provided an industrially suitable process for preparing a
4-halocatechol compound, which is capable of preparing the
4-halocatechol compound under mild conditions by a simple
and easy method with high yield:
Also, according to the present invention, it can be
provided a high purity 4-chloromethylenedioxybenzene which
is optimum for using it as a starting material or a synthe-
tic intermediate for a medicine, an agricultural chemical,
etc., and does not substantially contain impurities such as
methylenedioxybenzene which is a remaining starting materi-
al, or 4,5-dichloromethylenedioxybenzene which is a by-pro-
duct, etc., and a process for preparing the same. As a
method of leading these compounds to a medicine, an agri-

cultural chemical, etc., for example, WO 02/163521 Al, etc.
can be referred to.
BEST MODE FOR CARRYING OUT THE INVENTION
[0012]
The catechol compound to be used in the reaction of
the present invention is represented by the above-mentioned
formula (1) . In the formula (1) , R1 and R2 may be the same
or different from each other and each represents a hydrogen
atom or a hydrocarbon group. As the hydrocarbon group,
there may be mentioned, for example, an alkyl group having
1 to 10 carbon atoms such as a methyl group, ethyl group,
propyl group, butyl group, pentyl group, hexyl group,
heptyl group, octyl group, nonyl group, decyl group, etc.;
a cycloalkyl group having 3 to 8 carbon atoms such as a
cyclopropyl group, cyclobutyl group, cyclopentyl group,
cyclohexyl group, cycloheptyl group, cyclooctyl group,
etc. , an aralkyl group in which an aryl group is bonded to
an alkyl group having 1 to 6 carbon atoms such as a
phenethyl group, phenylpropyl group, etc.; an aryl group
having 6 to 2 0 carbon atoms such as a phenyl group, p-tolyl
group, naphthyl group, anthryl group, etc. Incidentally,
these groups contain various kinds of isomers. Also, R1
and R2 may be bonded to each other to form a ring, and the
ring formed by bonding may be mentioned, for example, those
which contain an alkylene group having 1 to 3 carbon atoms
such as a methylenedioxy ring, ethylenedioxy ring, propyl-
enedioxy ring, etc. In the present invention, among these,
particularly preferred is that wherein R1 and R2 are bonded
together to form a methylene group.
[0013]
Also, R3 , R4 and R5 each represent groups which do
not participate in the reaction, and more specifically,
there may be mentioned, for example, a hydrogen atom, alkyl
group, cycloalkyl group, aralkyl group, aryl group, halogen
atom, hydroxyl group, alkoxyl group, alkylthio group, nitro

group, cyano group, carbonyl group, amino group or carboxyl
group.
[0014]
As the above-mentioned alkyl group, there may be
mentioned, for example, an alkyl group having 1 to 10
carbon atoms such as a methyl group, ethyl group, propyl
group, butyl group, pentyl group, hexyl group, heptyl
group, octyl group, nonyl group, decyl group, etc. Inci-
dentally, these groups contain various kinds of isomers.
[0015]
As the above-mentioned cycloalkyl group, there may be
mentioned, for example, a cycloalkyl group having 3 to 8
carbon atoms such as a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group, etc.
[0016]
As the above-mentioned aralkyl group, there may be
mentioned, for example, an aralkyl group in which an aryl
group is bonded to an alkyl group having 1 to 6 carbon
atoms such as a benzyl group, phenethyl group, phenylpropyl
group, etc. Incidentally, these groups contain various
kinds of isomers.
[0017]
As the above-mentioned aryl group, there may be
mentioned, for example, an aryl group having 6 to 2 0 carbon
atoms such as a phenyl group, p-tolyl group, naphthyl
group, anthryl group, etc. Incidentally, these groups
contain various kinds of isomers.
[0018]
As the above-mentioned halogen atom, there may be
mentioned, for example, a fluorine atom, chlorine atom,
bromine atom and iodine atom.
[0019]
As the above-mentioned alkoxyl group, there may be
mentioned, for example, an alkoxyl group having 1 to 10
carbon atoms such as a methoxyl group, ethoxyl group,

propoxyl group, etc. Incidentally, these groups contain
various kinds of isomers.
[0020]
As the above-mentioned alkylthio group, there may be
mentioned, for example, an alkylthio group having 1 to 10
carbon atoms such as a methylthio group, ethylthio group,
propylthio group, etc. Incidentally, these groups contain
various kinds of isomers.
[0021]
The 1,3-dihalo-5,5-dimethylhydantoin to be used in
the reaction of the present invention is represented by the
above-mentioned formula (2). In the formula (2), X is a
halogen atom, and there may be mentioned, for example, a
fluorine atom, chlorine atom, bromine atom and iodine atom,
preferably a chlorine atom and bromine atom.
[0022]
An amount of the above-mentioned 1,3-dihalo-5,5-
dimethylhydantoin to be used is preferably 0.4 to 1.3 mol,
more preferably 0.45 to 1.15 mol based on 1 mol of the
catechol compound.
[0023]
The reaction of the present invention is desirably
carried out in the presence of a solvent, and as the
solvent to be used, it is not particularly limited so long
as it does not inhibit the reaction, and there may be
mentioned, for example, water; a carboxylic acid such as
formic acid, acetic acid, propionic acid, etc.; an alcohol
such as methanol, ethanol, isbpropyl alcohol, t-butyl
alcohol, etc.; a ketone such as acetone, methyl ethyl
ketone, methyl isobutyl ketone, etc.; an amide such as N,N-
dimethylformamide, N,N-dimethylacetamide, N-methylpyrroli-
done, etc.; a urea such as N,N'-dimethylimidazolidinone,
etc.; a sulfoxide such as dimethylsulfoxide, etc.; a
sulfone such as sulfolane, etc.; a nitrile such as aceto-
nitr'ile, propionitrile, etc.; an ether such as diethyl
ether, diisopropyl ether, tetrahydrofuran, dioxane, etc.;

an aromatic hydrocarbon such as benzene, toluene, xylene,
etc., preferably a carboxylic acid, more preferably acetic
acid is used. Incidentally, these organic solvents may be
used alone or in combination of two or more kinds.
[0024]
An amount of the above-mentioned solvent to be used
is preferably 0.5 to 100 ml, more preferably 1 to 50 ml
based on 1 g of the catechol compound.
[0025]
The reaction of the present invention can be carried
out, for example, by a method in which a catechol compound,
1,3-dihalo-5,5-dimethylhydantoin and a solvent are mixed,
and they are reacted under stirring, and the like. A
reaction, temperature at that time is preferably -2 0 to
200°C, more preferably 0 to 120°C, and a reaction pressure
is not particularly limited.
[0026]
A 4-halocatechol compound can be obtained according
to the reaction of the present invention, and the compound
can be isolated and purified by a usual process, for exam-
ple, neutralization, extraction, filtration, concentration,
distillation, recrystallization, crystallization, column
chromatography, etc., after completion of the reaction.
[0027]
Incidentally, the reaction of the present invention
is a particularly advantageous process for preparing, for
example, a 4-halocatechol compound such as 4-halomethyl-
enedioxybenzene, etc., from the corresponding catechol
compound which is weak to an acid such as methylenedioxy-
benzene, etc.
[0028]
The high purity 4-chloromethylenedioxybenzene of the
present invention means 4-chloromethylenedioxybenzene in
which a content of me.thylenedioxybenzene is 0.5% by weight
or less and a content of 4,5-dichloromethylenedioxybenzene
is 0.5% by weight or less. In the present invention, it is

preferred that a content of methylenedioxybenzene is 0.1%
by weight or less and a content of 4,5-dichloromethylene-
dioxybenzene is 0.1% by weight or less, more preferably a
content of methylenedioxybenzene is 0.01% by weight or less
and a content of 4,5-dichloromethylenedioxybenzene is 0.01%
by weight or less.
[0029]
The high purity 4-chloromethylenedioxybenzene of the
present invention can be obtained by reacting a chlorinat-
ing agent to methylenedioxybenzene, and then, subjecting to
purification by distillation.
[0030]
As the above-mentioned method of purification by
distillation, it can be carried out, for example, by fill-
ing at least one filler selected from the group consisting
of Sulzerpack (Registered trademark), Pall ring, Mellapak
(Registered trademark), Mellacarbon (Registered trademark),
Mellajourl (Registered trademark) in a distillation tower
of a distillation device with one or a plural number of
them,.and subjecting to purification by distillation, and
the like. Incidentally, the above-mentioned filler is
preferably filled with two number of theoretical plate or
more. A temperature or a pressure at the time of purifica-
tion by distillation is not particularly limited.
[0031]
As the above-mentioned chlorinating agent, there may
be mentioned, for example, sulfuryl chloride, 1,3-dichloro-
5,5-dimethylhydantoin, trichloroisocyanuric acid, t-butyl
hypochlorite, etc, and 1,3-dichloro-5,5-dimethylhydantoin
is preferably used. Incidentally, these chlorinating
agents may be used alone or in combination of two or more
kinds.
[0032]
An amount of the above-mentioned chlorinating agent
to be used is preferably 0.4 to 1.3 mol, more preferably
0.45 to 1.15 mol based on 1 mol of methylenedioxybenzene.

[0033]
The reaction of the above-mentioned methylenedioxy-
benzene and the chlorinating agent is desirably carried out
in the presence of a solvent. The solvent to be used is
not particularly limited so long as it does not inhibit the
reaction, and there may be mentioned, for example, water; a
carboxylic acid such as formic acid, acetic acid, propionic
acid, etc.; an alcohol such as methanol, ethanol, isopropyl
alcohol, t-butyl alcohol, etc.; a ketone such as acetone,
methyl ethyl ketone, methyl isobutyl ketone, etc.; an amide
such as N,N-dimethylformamide, N,N-dimethylacetamide, N-
methylpyrrolidone, etc.; a urea such as N,N'-dimethylimid-
azolidinone, etc.; a sulfoxide such as dimethylsulfoxide,
etc.; a sulfone such as sulfolane, etc.; a nitrile such as
acetonitrile, propionitrile, etc.; an ether such as diethyl
ether, diisopropyl ether, tetrahydrofuran, dioxane, etc.;
an aromatic hydrocarbon such as benzene, toluene, xylene,
et:c. Incidentally, these organic solvents may be used
alone or in combination of two or more kinds.
[0034]
An amount of the above-mentioned solvent to be used
is preferably 0.5 to 10 0 ml, more preferably 1 to 5 0 ml
based on 1 g of methylenedioxybenzene.
[0035]
The reaction of the above-mentioned methylenedioxy-
benzene and the chlorinating agent can be carried out, for
example, by a method in which methylenedioxybenzene, a
chlorinating agent and a solvent are mixed, and they are
reacted under stirring, and the like. A reaction tempera-
ture at that time is preferably -20 to 200°C, more prefer-
ably 0 to 120°C, and a reaction pressure is not particular-
ly limited.
EXAMPLES .'
[0036]
Next, the present invention will be explained more

specifically by referring to Examples, but the scope of the
present invention is not limited by these.
[0037]
Example 1 (Synthesis of 4-chloromethylenedioxybenzene)
In a flask made of glass having an inner volume of
10 0 ml and equipped with a stirring device, a thermometer
and a reflux condenser were charged 244.2 g (2.0 mol) of
methylenedioxybenzene and 122 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 55°C.
Then, while maintaining the liquid temperature from 6 0 to
90°C, 216.7 g (1.1 mol) of 1,3-dichloro-5,5-dimethyl-
hydantoin was added dropwise to the mixture little by
little, and the mixture was reacted at 70°C for 1 hour
under stirring. After completion of the reaction, the .
reaction mixture was cooled to room temperature, 245 ml of
hexane and 24 5 ml of water were added to the reaction
mixture and the resulting mixture was stirred, and the
organic layer was separated. The obtained organic layer
was washed with 10% aqueous sodium hydroxide solution and
10% aqueous sodium chloride solution, and then dried over
anhydrous magnesium sulfate. After filtration, the
filtrate was concentrated under reduced pressure, and the
concentrate was distilled under reduced pressure (85°C,
1067 to 1333Pa) to obtain 227.3 g of 4-chloromethylene-
dioxybenzene -as colorless liquid (Isolation yield; 7-2.6%).
Incidentally, physical properties of 4-chloromethyl-
enedioxybenzene were as follows.
[0038]
EI-MS (m/e); 156 (M),.158 (M+2)
'H-NMR (DMSO-ds, 5 (ppm)); 7.05 (1H„ dd, J=2.0, 0.5Hz),
6.93 (1H, dd, J=8.3, 0.5Hz), 6.87 (1H, dd, J=8.3, 2.0Hz),
6.07 (2H, s)
[0039]
Example 2 (Synthesis of 4-chloromethylenedioxybenzene)
In a flask made of glass having an inner volume of 25
ml and equipped with a stirring device, a thermometer and a

reflux condenser were charged 1.22 g (10 mmol) of methyl-
enedioxybenzene and 1.22 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 60°C.
Then, while maintaining the liquid temperature from 60 to
90°C, 1.13 g (5.5 mmol) of l,.3-dichloro-5,5-dimethyl-
hydantoin was added dropwise to the mixture little by
little, and the mixture was reacted at 70°C for 1 hour
under stirring. After completion of the reaction, when the
reaction mixture was analyzed (absolute quantitative
analysis) by high performance liquid chromatography, 1.34 g
of 4-chloromethylenedioxybenzene was found to be formed
(Reaction yield; 85.6%).
[0040]
Comparative example 1 (Synthesis of 4-chloromethylenedioxy-
benzene)
In a flask made of glass having an inner volume of
500 ml and equipped with a stirring device, a thermometer
and a reflux condenser was charged 244.2 g (2.0 mol) of
methylenedioxybenzene under argon atmosphere. Then, 405.0
g (3.0 mol) of sulfuryl chloride was gradually added drop-
wise to the mixture while maintaining the liquid tempera-
ture from 3 0 to 35°C, and the mixture was reacted at 3 0°C
for 4 hours under stirring. After completion of the
reaction/ the reaction mixture was cooled to room tempera-
ture, 2 00 ml of hexane was added to the reaction mixture,
the obtained organic layer was washed with 200 g of 32%
aqueous sodium thiosulfate solution twice and 200 g of 10%
aqueous sodium hydrogen carbonate solution, and then dried
over anhydrous magnesium sulfate. After filtration, the,
filtrate was concentrated under reduced pressure, and the
concentrate was distilled under reduced pressure (80 to
85°C, 933 to 1067Pa) to obtain 192.1 g of 4-chloromethyl-
enedioxybenzene as colorless liquid (Isolation yield;
59.7%).
[0041]
Example 3 (Synthesis of 4-bromomethylenedioxybenzene).

In a flask made of glass having an inner volume of
500 ml and equipped with a stirring device, a thermometer
and a reflux condenser were charged 61.1 g (0.5 mol) of
methylenedioxybenzene and 30 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 60°C.
Then, while maintaining the liquid temperature from 6 0 to
90°C, 78.6 g (0.275 mol) of 1,3-dibromo-5,5-dimethyl-
hydantoin was added dropwise to the mixture little by
little, and the mixture was reacted at 70°C for 1 hour
under stirring. After completion of the reaction, the
reaction mixture was cooled to room temperature, and 2 00 g
(1.0 mol) of 20% aqueous sodium hydroxide solution was
added to the mixture and stirred. Then, the reaction
mixture was filtered, the organic layer was separated, and
the organic layer was distilled under reduced pressure
(93°C, 12 00Pa) to obtain 71.2 g of 4-bromomethylenedioxy-
benzene as colorless liquid (Isolation yield; 70.8%).
Incidentally, physical properties of 4-bromomethyl-
enedioxybenzene were as follows.
[0042]
EI-MS (m/e); 200 (M), 202 (M+2)
^-NMR (DMS0-d6 , 8 (ppm) ) ; 7.16 (1H, d, J=1.9Hz), 7.00 (1H,
dd, J=8.3, 2.2Hz), 6.88 (1H, d, J=8.3Hz), 6.06 (2H, s)
[0043]
Example 4 (Synthesis of 4-bromoveratrol (4-bromo-l,2-
dimethoxybenzene))
In a flask made of glass having an inner volume of
100 ml and equipped with a stirring device and a thermo-
meter were charged 13.8 g (100 mmol) of veratrol and 21.0 g
(3 50 mmol) of acetic acid under argon atmosphere, and the
liquid temperature was cooled to 10 to 20°C. Then, 17.2 g
(60 mmol) of 1,3-dibromo-5,5-dimethylhydantoin was added
dropwise little by little to the mixture over 3 0 minutes,
and the mixture was reacted at 10 to 2 0°C for 1 hour.
After completion of the reaction, 25 ml of toluene was
added to the mixture, the mixture was stirred at 10. to 20°C

for 3 0 minutes, and solids of the precipitated hydantoin
and monobromohydantoin were removed by filtration. The
filtrate was apportioned to 4 fractions,' the first fraction
was added to a mixed solvent of toluene (50 ml)-water (25
ml) to extract the desired compound into the toluene layer
and acetic acid was removed by the aqueous layer. To the
obtained toluene extract was added 2 5 ml of water, subse-
quently it was combined with the second fraction of the
filtrate, and the same extraction treatment was carried out
to obtain a toluene extract. With regard to the remaining
two fractions, the same extraction treatment as above was
carried out, and the whole filtrates were subjected to
separation treatment. The obtained toluene extract was
washed twice with 25 ml of water, once with 20 ml of
saturated aqueous sodium hydrogen carbonate solution, and
finally once with 3 5 ml of saturated saline solution.
Incidentally, when the obtained toluene extract was
analyzed (absolute quantitative analysis) by high perform-
ance liquid chromatography, 19.8 g (Yield: 91.6%) of 4-
bromoveratrol was found to be formed. The toluene extract
was concentrated, and the obtained concentrate (crude 4-
bromoveratrol) was distilled under reduced pressure (5
mmHg, bp 99 to 100°C), then, 15.8 g of 4-bromoveratrol was
obtained as pale yellowish liquid (Isolation yield: 72.9%).
Incidentally, physical properties of 4-bromoveratrol
were as follows.
EI-MS (m/e); 216 (M) , 218. (M+2)
^-NMR (CDC13, 5 (ppm) ) ; 7.03 (1H, dd, J=2 .4, 8.5Hz), 6.98
(1H, d, J=2.4Hz), 6.74 (1H, d, J=8.5Hz), 3.87 (3H, s) , 3.86
(3H, s) ...'.•
[0044]
Example 5 (Synthesis of high purity 4-chloromethylenedioxy-
benzene)
In a flask made of glass haying an inner volume of
2000 ml and equipped with a stirring device, a thermometer
and a reflux condenser were charged 488.4 g (4.0 mol) of

methylenedioxybenzene and 24 0 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 60°C.
Then, while maintaining the liquid temperature from 60 to
90°C, 433.4 g (2.2 mol) of 1,3-dichloro-5,5-dimethylhydan-
toin was added dropwise to the mixture little by little,
and the mixture was reacted at 70°C for 1 hour under
stirring. After completion of the reaction, the reaction
mixture was cooled to room temperature, and 1000 g (6.25
mol) of 25% aqueous sodium hydroxide solution was added to
the mixture and then stirred. Then, the organic layer was
separated, and the organic layer was distilled under
reduced pressure (84°C, 1067 to 1200Pa) using a distilla-
tion device in which three Sulzerpacks (55 mmH x 2.5 mm)'
had been filled therein to obtain 420.7 g of 4-chloro-
methylenedioxybenzene purified by distillation as colorless
liquid (Isolation yield; 67.2%). Incidentally, when the
obtained 4-chloromethylenedioxybenzene was analyzed
(absolute quantitative analysis) by high performance liquid
chromatography, only 0.17% by weight of the remaining
starting material methylenedioxybenzene and 0.35% by weight
of by-product 4,5-dichloromethylenedioxybenzene had been
contained in 4-chloromethylenedioxybenzene based on the
amount of the 4-chloromethylenedioxybenzene.
[0045]
Example 6- (Synthesis of high purity 4-chloromethylenedioxy-
benzene)
In a flask made of glass having an inner volume of
1000 ml and equipped with a stirring device, a thermometer
and a reflux condenser were charged 244.2 g (2.0 mol) of
methylenedioxybenzene and 122 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 55°C.
Then, while maintaining the liquid temperature from 60 to
95°C, 216.7 g (1.1 mol) of 1,3-dichloro-5,5-dimethylhydan-
toin was added dropwise to the mixture little by little,
and the mixture was reacted at 70°C for 1 hour under
stirring. After completion of the reaction, the reaction

mixture was cooled to room temperature, 245 ml of hexane
and 245 ml of water were added to the reaction mixture, the
resulting mixture was stirred, and the organic layer was
separated. The obtained organic layer was washed with 100
g (0.25 mol) of 10% aqueous sodium hydroxide solution and
100 g (0.25 mol) of 10% aqueous sodium chloride solution,
and then, dried over anhydrous magnesium sulfate. After
filtration, the filtrate was concentrated under reduced
pressure, and the concentrate was subjected to distillation
under reduced pressure (84°C, 1067 to 1200Pa) by using a
distillation device in which three Sulzerpacks (55 mmH x
2.5 mm<|>) had been filled in a distillation tower to obtain
227.3 g of 4-chloromethylenedioxybenzene which had been
purified by distillation as colorless liquid (Isolation
yield; 72.6%). Incidentally, when the product was analyzed
in the same manner as in Example 5, only 0.03% by weight of
the remaining starting material methylenedioxybenzene and
0.01% by weight or less of by-product 4,5-dichloromethyl-
enedioxybenzene had been contained in 4-chloromethylene-
dioxybenzene based on an amount of the 4-chloromethylene-
dioxybenzene .
[0046]
Example 7 (Synthesis of high purity 4-chloromethylenedioxy-
benzene)
In a flask made of glass having an inner volume of
500 ml and equipped with a stirring device, a thermometer
and a reflux condenser were charged 122.1 g (2.0 mol) of
methylenedioxybenzene and 122 g of acetic acid under argon
atmosphere, and the liquid temperature was raised to 55°C.
Then, while maintaining the liquid temperature from 60 to
75°C, 108.4 g (0.55 mol) of 1,3-dichloro-5,5-dimethylhydan-
toin was added dropwise to the mixture little by little,
and the mixture was reacted at 70°C for 1 hour under
stirring. After completion of the reaction, the reaction
mixture was cooled to room temperature, 12 0 ml of hexane
and 120 ml of water were added to the reaction mixture and

the mixture was stirred, and the organic layer was
separated. The obtained organic layer was washed with 100
g (0.25 mol) of 10% aqueous sodium hydroxide solution.and
100 g (0.25 mol)~ of 10% aqueous sodium chloride solution,
and then, dried over anhydrous magnesium sulfate. After
filtration, the filtrate was concentrated under reduced
pressure, and the. organic layer was distilled under reduced
pressure (86°C, 1333Pa) using a distillation device in
which three Sulzerpacks (55 mmH x 2.5 mm) had been filled
therein to obtain 97.1 g of 4-chloromethylenedioxybenzene
purified by distillation as colorless liquid (Isolation
yield; 61.6%). Incidentally, when the product was analyzed
in the same manner as in Example 5, only 0.01% by weight or
less of the remaining starting material methylenedioxy-
benzene and 0.01% by weight or less.of by-product 4,5-
dichloromethylenedioxybenzene had been contained in 4-
chloromethylenedioxybenzene based on the amount of the 4-
chloromethylenedioxybenzene.
[0047]
Example 8 (Preparation of high purity 4-chloromethylene-
dioxybenzene by distillation and purification of crude 4-
chloromethylenedioxybenzene)
When 594.86 g of crude 4-chloromethylenedioxybenzene
which contains 0.96% by weight of the remaining starting
material methylenedioxybenzene and 1.84% by weight of the
by-product 4,5-dichloromethylenedioxybenzene was distilled
under reduced pressure (80 to 81 °C, 9.33 to. 1066Pa) using a
distillation device in which two Sulzerpacks (55 mmH x 2.5
mm<)>) had been filled in a distillation tower, 365.59 g of
4-chloromethylenedioxybenzene purified by distillation was
obtained as colorless liquid. Incidentally, when the
product was analyzed in the same manner as in Example 5,
only 0.-10% by weight of the remaining starting material
methylenedioxybenzene and 0.09% by weight of by-product
4,5-dichloromethylenedioxybenzene had been contained:in 4-
chloromethylenedioxybenzene based on the amount of the 4-

chloromethylenedioxybenzene.
[0048]
Example 9 (Synthesis of high purity 4-chloromethylenedioxy-
benzene by distillation and purification of crude 4-chloro-
methylenedioxybenzene)
When 142.74 g of crude 4-chloromethylenedioxybenzene
which contains 6.41% by weight of the remaining starting
material methylenedioxybenzene and 1.22% by weight of the
by-product 4,5-dichloromethylenedioxybenzene was distilled
under reduced pressure (85°C, 1333Pa) using a distillation
device in which three Sulzerpacks (55 mmH x 2.5 mm<|)) had
been filled in a distillation tower, 104.03 g of 4-chloro-
methylenedioxybenzene purified by distillation was obtained
as colorless liquid. Incidentally, when the product was
analyzed in the same manner as in Example 5, only 0.01% by
weight or less of the remaining starting material methyl-
enedioxybenzene and 0.01% by weight or less of by-product
4,5-dichloromethylenedioxybenzene had been contained in 4-
chloromethylenedioxybenzene based on the amount of the 4-
chloromethylenedioxybenzene.
UTILIZABILITY IN INDUSTRY
[0049]
The present invention relates to a novel process for
preparing a 4-halocatechol compound. The 4-halocatechol
compound is a compound useful as a starting material or a
synthetic intermediate for a medicine, an agricultural
chemical, etc.
The present invention also relates to high purity 4-
chloromethylenedioxybenzene. and a process for preparing the
same. The high purity 4-chloromethylenedioxybenzene is a
compound useful as a starting material or a synthetic
intermediate for a medicine, an agricultural chemical, etc.

We Claim:
1. A process for preparing a 4-halocatechol compound represented by the formula (3):

wherein R1 and R2 are bonded to each other to form a methylene group, and
R3, R4 and R5 each represent groups which do not participate in the reaction,
which comprises reacting a catechol compound represented by the formula (1):

wherein R1, R2, R3, R4 and R5 have the same meanings as defined above,
with a l,3-dihalo-5,5-dimethylhydantoin represented by the formula (2):

wherein X represents a halogen atom,
in a carboxylic acid.
2. The process for preparing a 4-halocatechol compound as claimed in Claim 1, wherein the
carboxylic acid is acetic acid.
3. The process for preparing a 4-halocatechol compound as claimed in Claim 1 or 2, wherein the
catechol compound is methylenedioxybenzene.

4. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 3,
wherein X is a chlorine atom or a bromine atom.
5. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 4,
wherein the l,3-dihalo-5,5-dimethylhydantoin is used in an amount of 0.4 to 1.3 mol based on 1
mol of the catechol compound.
6. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 4,
wherein the l,3-dihalo-5,5-dimethylhydantoin is used in an amount of 0.45 to 1.15 mol based on 1
mol of the catechol compound.
7. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 6,
wherein the reaction is carried out at a temperature of -20 to 200°C.
8. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 6,
wherein the reaction is carried out at a temperature of 0 to 120°C.
9. The process for preparing a 4-halocatechol compound as claimed in any one of Claims 1 to 8,
wherein the 4-halocatechol compound is 4-chloromethylenedioxybenzene or 4-
bromomethylenedioxybenzene.

(54) Tide: METHOD FOR PRODUCING 4-HALOCATECHOL COMPOUND
(57) Abstract: Disclosed is a method for producing a 4-halocatechol compound, which is characterized in that a catechol compound
is reacted with l,3-dihalo-5,5-dimethylhydantoin. Also disclosed are a high-purity 4-chloromethylenedioxybenzene which is characterized
in that the methylenedioxybenzene content is not more than 0.5% by mass and the 4,5-dichloromethylenedibxybenzene
content is not more than 0.5% by mass, and a method for producing such a high-purity 4-chloromethylenedioxybenzene.