Title of Invention

METHOD FOR PRODUCING HALOGEN-SUBSTITUTED BENZENEDIMETHANOL

Abstract A method for producing a halogen-substituted benzenedimethanol represented by the formula (2): wherein X1 to X4 are the same or different and independently represent a halogen atom or the like, provided that at least one of X1 to X4 is a halogen atom, by reacting a halogen-substituted terephthalic acid diester represented by the formula (1): wherein R1 and R2 are the same or different and independently represent a C1-C20 alkyl group which may have a substitutent or substituents, and X1 to X4 is the same as defined above. with a borohydride compound in the presence of an alcohol which comprises adding the alcohol into a mixture of the halogen-substituted terephthalic acid diester represented by the formula (1), the borohydride compound and a solvent.
Full Text DESCRIPTION
METHOD FOR PRODUCING HALOGEN-SUBSTITUTED BENZENEDIMETHANOL
Technical Field
The present invention relates to a method for
producing a halogen-substituted benzenedimethanol.
Background Art
A halogen-substituted benzenedimethanol is an
important compound as raw materials and intermediates of
pharmaceuticals and agrichemicals, and especially, US
4927852 discloses 2,3,5,6-tetrafluorobenzenedimethanol is
useful as an intermediate of household pesticides.
As a method for producing 2,3,5,6-
tetrafluorobenzenedimethanol, for example, US 4927852
discloses a method comprising conducting bromination of
2,3,5,6-tetrafluoroparaxylene followed by conducting
acetoxylation and then hydrolysis. GB 2127013 A discloses
a method comprising reacting 2,3,5,6-
tetrafluoroterephthalic chloride with sodium borohydride.
US 5583131 discloses a method comprising reacting 2,3,5,6-
tetrafluoroterephthalic acid with borane tetrahydrofuran
complex and US 6759558 discloses a method comprising
reacting 2,3,5,6-tetrafluoroterephthalic acid with sodium

borohydride in the presence of dimethyl sulfate or sulfuric
acid. JP 2002-20332 A discloses a method comprising
hydrogenating 2,3,5,6-tetrafluoroterephthalonitrile
followed by conducting diazotization and then hydrolysis.
Disclosure of the Invention
The present invention provides a method for producing
a halogen-substituted benzenedimethanol represented by the
formula (2):

wherein X1 to X4 are the same or different and
independently represent a hydrogen or halogen atom,
provided that at least one of X1 to X4 is a halogen atom,
by reacting a halogen-substituted terephthalic acid diester
represented by the formula (1):

wherein R1 and R2 are the same or different and
independently represent an optionally substituted C1-C20
alkyl group and the substitutent of the alkyl group is a
fluorine atom; a C1-C20 alkoxy group which is optionally
substituted with a halogen atom or atoms; a C6-C20 aryl

group which is optionally substituted with a C1-C6 alkoxy
group or groups; a C6-C20 aryloxy group which is optionally
substituted with a C1-C6 alkoxy group or groups or phenoxy
group or groups; or a C7-C20 aralkyloxy group which is
optionally substituted with a C1-C6 alkoxy group or groups
or phenoxy group or groups, and X1 to X4 is the same as
defined above,
with a borohydride compound in the presence of an alcohol
which comprises adding the alcohol into a mixture of the
halogen-substituted terephthalic acid diester represented
by the formula (1), the borohydride compound and a solvent.
Best Mode for Carrying Out the Present Invention
In the halogen-substituted terephthalic acid diester
represented by the formula (1) (hereinafter, simply
referred to as the halogen-substituted terephthalic acid
diester (1)), in the formula, R1 and R2 are the same or
different and represent a C1-C20 alkyl group which may have
a substituent or substituents. Herein, the above-mentioned
substituent is a fluorine atom; a C1-C20 alkoxy group which
is optionally substituted with a halogen atom or atoms; a
C6-C20 aryl group which is optionally substituted with a
C1-C6 alkoxy group or groups; a C6-C20 aryloxy group which
is optionally substituted with a C1-C6 alkoxy group or
groups or a phenoxy group or groups; or a C7-C20 aralkyloxy

group which is optionally substituted with a C1-C6 alkoxy
group or groups or phenoxy group or groups. X1 to X are
the same or different and independently represent a
hydrogen or halogen atom, provided that at least one of X1
to X4 is a halogen atom.
Examples of the C1-C20 alkyl group include a straight
chain, branched chain or cyclic alkyl group such as a
methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-
butyl, tert-butyl, n-pentyl, n-decyl, cyclopropyl, 2,2-
dimethylcyclopropyl, cyclopentyl, cyclohexyl and menthyl
group.
The alkyl group may have a substituent or substituents
and the substituent is a fluorine atom; a C1-C20 alkoxy
group which is optionally substituted with a halogen atom
or atoms; a C6-C20 aryl group which is optionally
substituted with a C1-C6 alkoxy group or groups; a C6-C20
aryloxy group which is optionally substituted with a C1-C6
alkoxy group or groups or a phenoxy group or groups; or a
C7-C20 aralkyloxy group which is optionally substituted
with a C1-C6 alkoxy group or groups or phenoxy group or
groups.
Examples of the halogen atom include a fluorine,
chlorine and bromine atom.
Examples of the C1-C20 alkoxy group which is
optionally substituted with a halogen atom or atoms include

a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,
isobutoxy, sec-butoxyl, tert-butoxy, n-hexyloxy, n-decyloxy
and trifluoromethoxy group.
Examples of the C6-C20 aryl group which is optionally
substituted with a C1-C6 alkoxy group or groups include a
phenyl, 4-methylphenyl and 4-methoxyphenyl group.
Examples of the C6-C20 aryloxy group which is
optionally substituted with a C1-C6 alkoxy group or groups
or a phenoxy group or groups include a phenoxy, 2-
methylphenoxy, 4-methylphenoxy, 4-methoxyphenoxy and 3-
phenoxyphenoxy group.
Examples of the C7-C20 aralkyloxy group which is
optionally substituted with a C1-C6 alkoxy group or groups
or a phenoxy group or groups include a benzyloxy, 4-
methylbenzyloxy, 4-methoxybenzyloxy and 3-phenoxybenzyloxy
group.
Examples of the alkyl group substituted with the
substituent or substituents include a fluoromethyl,
trifluoromethyl, methoxymethyl, ethoxymethyl, methoxyethyl,
benzyl, phenoxymethyl and benzyloxymethyl group.
Examples of the halogen-substituted terephthalic acid
diester (1) include dimethyl 2-fluoroterephthalate,
dimethyl 2-chloroterephthalate, dimethyl 2,5-
difluoroterephthalate, dimethyl 2,6-difluoroterephthalate,
dimethyl 2,3-difluoroterephthalate, dimethyl 2,5-

dichloroterephthalate, dimethyl 2,6-dichloroterephthalate,
dimethyl 2,3-dichloroterephthalate, dimethyl 2,3,5-
trifluoroterephthalate, dimethyl 2,3,5-
trichloroterephthalate, dimethyl 2,3,5,6-
tetrafluoroterephthalate, diethyl 2,3,5,6-
tetrafluoroterephthalate, di(n-propyl) 2,3,5,6-
tetrafluoroterephthalate, diisopropyl 2,3,5,6-
tetrafluoroterephthalate, di(n-butyl) 2,3,5,6-
tetrafluoroterephthalate, di(tert-butyl) 2,3,5,6-
tetrafluoroterephthalate, dimethyl 2,3,5,6-
tetrachloroterephthalate, diethyl 2,3,5,6-
tetrachloroterephthalate, di(n-propyl) 2,3,5,6-
tetrachloroterephthalate, diisopropyl 2,3,5,6-
tetrachloroterephthalate, di(n-butyl) 2,3,5,6-
tetrachloroterephthalate, di(tert-butyl) 2,3,5,6-
tetrachloroterephthalate, and dimethyl 2,3,5-trifluoro-6-
chloroterephthalate. The halogen-substituted terephthalic
acid diester (1) wherein R1 and R2 are the same C1-C6 alkyl
groups is preferable.
The halogen-substituted terephthalic acid diester (1)
can be produced, for example, by a method described in EP
0140482 B.
Examples of the borohydride compound include an alkali
metal borohydride such as sodium borohydride, lithium
borohydride and potassium borohydride and an alkaline earth

metal borohydride such as calcium borohydride and magnesium
borohydride. The alkali metal borohydride is preferable
and sodium borohydride is more preferable.
A commercially available borohydride compound may be
used and those prepared according to method described in US
3471268, Inorganic Chemistry, 1981, 20, 4454 and the like
may be used. As the borohydride compound, those priviously
prepared may be used and it may be prepared in the reaction
system.
The amount of the borohydride compound to be used is
usually 2 to 5 moles, preferably 2 to 2.5 moles relative to
1 mole of the halogen-substituted terephthalic acid diester
(1).
The alcohol means an organic compound wherein one or
more hydrogen atom of a hydrocarbon is substituted with a
hydroxyl group. Examples thereof include an aliphatic
alcohol such as methanol, ethanol, n-propanol, isopropanol,
n-butanol and tert-butanol, and an aromatic alcohol such as
phenol and benzyl alcohol, and the aliphatic alcohol is
preferable and methanol is more preferable. The amount of
the alcohol to be used is not particularly limited and
large excess thereof, for example, 100 parts by weight
relative to 1 part of the halogen-substituted terephthalic
acid diester (1), may be used as the solvent and it is
practically 1 to 50 moles relative to 1 mole of the

halogen-substituted terephthalic acid diester (1).
The present reaction is carried out in a solvent.
Examples of the solvent include an ether solvent such as
diethyl ether, methyl tert-butyl ether, tetrahydrofuran,
dioxane and diisopropyl ether, and an aromatic hydrocarbon
solvent such as toluene, xylene and chlorobenzene. The
alcohol can be used as the solvent as described above. The
amount of the solvent to be used is not particularly
limited and it is practically not more than 100 parts by
weight relative to 1 part of the halogen-substituted
terephthalic acid diester (1).
The reaction is conducted by adding the alcohol to a
mixture obtained by mixing the halogen-substituted
terephthalic acid diester (1), the borohydride compound and
the solvent.
The reaction is usually carried out under ordinary
pressure conditions, and may be carried out under
pressurized conditions. The progress of the reaction can
be confirmed by a conventional analytical means such as gas
chromatography and high performance liquid chromatography.
After completion of the reaction, for example, a
reaction liquid is mixed with an aqueous solution of a
mineral acid such as hydrochloric acid, sulfuric acid,
phosphoric acid and nitric acid, if necessary, followed by
conducting treatment such as neutralizing, extracting using

an organic solvent and concentrating to isolate a halogen-
substituted benzenedimethanol represented by the formula
(2) (hereinafter, simply referred to as the halogen-
substituted benzenedimethanol (2)). The halogen-
substituted benzenedimethanol (2) isolated may be further
purified by a conventional purification means such as
recrystallization and column chromatography.
Examples of the halogen-substituted benzenedimethanol
(2) thus obtained include
2-fluoro-1,4-benzendimethanol, 2-chloro-1,4-
benzendimethanol, 2,5-difluoro-1,4-benzendimethanol, 2,6-
difluoro-l,4-benzendimethanol, 2,3-difluoro-1,4-
benzendimethanol, 2,5-dichloro-l,4-benzendimethanol, 2,6-
dichloro-1,4-benzendimethanol, 2,3-dichloro-1,4-
benzendimethanol, 2,3,5-trifluoro-1,4-benzendimethanol,
2,3,5-trichloro-1,4-benzendimethanol, 2,3,5,6-
tetrafluorobenzendimethanol, 2,3,5,6-
tetrachlorobenzendimethanol, and 2,3,5-trifluoro-6-
chlorobenzendimethanol.
Examples
Example 1
Into a 200 ml flask, 2.61 g of sodium borohydride,
26.8 g of tetrahydrofuran and 8.94 g of dimethyl 2,3,5,6-
tetrafluoroterephthalate were charged. 26.7 g of methanol

was added dropwise thereto at an inner temperature of 55°C
over 80 minutes with stirring. After stirring at the same
temperature for 6.5 hours, the mixing was conducted at room
temperature for 20 hours. 24.5 g of 10% by weight
hydrochloric acid was added dropwise to the reaction liquid
at 25 to 30°C over 1 hour followed by stirring at the same
temperature for 1 hour. Further, 8 g of 23% by weight
aqueous sodium hydroxide was added thereto. The solution
obtained was concentrated, 100 g of water was added to the
residue obtained to extract three times with 70 g of ethyl
acetate and the organic layers obtained were mixed. To the
organic layer, magnesium sulfate anhydride was added and
dried. After filtering off magnesium sulfate, the filtrate
was concentrated to obtain 6.38 g of white crystals of
2,3,5,6-tetrafluorobenzenedimethanol. The crystals were
analyzed by the gas chromatography internal standard method
to find that the content of 2,3,5,6-
tetrafluorobenzenedimethanol was 92.5%. Yield: 84%.
Example 2
Into a 200 ml flask, 1.66 g of sodium borohydride, 20
g of methyl tert-butyl ether and 5.32 g of dimethyl
2,3,5,6-tetrafluoroterephthalate were charged. 18.0 g of
methanol was added dropwise thereto at an inner temperature
of 55°C over 3 hours with stirring. After stirring at the

same temperature for 5 hours, the resultant mixture was
cooled to room temperature. 16 g of 10% by weight
hydrochloric acid was added dropwise to the reaction liquid
at 25 to 30°C over 30 minutes followed by stirring at the
same temperature for 30 minutes. Further, 45% by weight
aqueous sodium hydroxide was added thereto to adjust to pH
8. Methanol and methyl tert-butyl ether were distilled
away from the solution obtained and 50 g of ethyl acetate
was added to the residue obtained to extract twice and the
organic layers obtained were mixed. To the organic layer,
magnesium sulfate anhydride was added and dried. After
filtering off magnesium sulfate, the filtrate was
concentrated to obtain 10 g of concentrated liquid. To the
concentrated liquid, 30 g of toluene was added and the
crystals were precipitated. The crystals was filtered and
dried to obtain 3.82 g of white crystals of 2,3,5,6-
tetrafluorobenzenedimethanol. The crystals were analyzed
by the liquid chromatography area percentage method to find
that the content of 2,3,5,6-tetrafluorobenzenedimethanol
was 95.5%. Yield: 87%.
Example 3
Into a 200 ml flask, 1.66 g of sodium borohydride, 18
g of tetrahydrofuran and 6.64 g of dimethyl 2,3,5,6-
tetrachloroterephthalate were charged. 18.0 g of methanol

was added dropwise thereto at an inner temperature of 55°C
over 3 hours with stirring. After stirring at the same
temperature for 5 hours, the resultant mixture was cooled
to room temperature. 16 g of 10% by weight hydrochloric
acid was added dropwise to the reaction liquid at 25 to
30°C over 30 minutes followed by stirring at the same
temperature for 30 minutes. Further, 45% by weight aqueous
sodium hydroxide was added thereto to adjust to pH 8.
Methanol and tetrahydrofuran were distilled away from the
solution obtained, and 50 g of ethyl acetate was added to
the residue obtained to repeat twice extraction and the
organic layers obtained were mixed. To the organic layer,
magnesium sulfate anhydride was added to conduct
dehydration and then, the solid was filtering off. The
filtrate was concentrated and to the residue obtained, 5 g
of toluene and 30 g of n-hexane were added and the crystals
were precipitated. The crystals was filtered and dried to
obtain 4.40 g of white crystals of 2,3,5,6-
tetrachlorobenzenedimethanol. The crystals were analyzed
by the liquid chromatography area percentage method to find
that the content of 2,3,5,6-tetrachlorobenzenedimethanol
was 99.6%. Further, the filtrate after filtering the
crystals was concentrated and the crystals precipitated
were filtered and dried to obtain 0.63 g of white crystals
of 2,3,5,6-tetrachlorobenzenedimethanol. The content of

2,3,5,6-tetrachlorobenzenedimethanol was 90.2%. Yield: 90%.

WE CLAIM:
1. A method for producing a halogen-substituted
benzenedimethanol represented by the formula (2):

wherein X1 to X4 are the same or different and
independently represent a hydrogen or halogen atom,
provided that at least one of X1 to X4 is a halogen atom,
by reacting a halogen-substituted terephthalic acid diester
represented by the formula (1):

wherein R1 and R2 are the same or different and
independently represent an optionally substituted C1-C20
alkyl group and the substitutent of the alkyl group is a
fluorine atom; a C1-C20 alkoxy group which is optionally
substituted with a halogen atom or atoms; a C6-C20 aryl
group which is optionally substituted with a C1-C6 alkoxy
group or groups; a C6-C20 aryloxy group which is optionally
substituted with a C1-C6 alkoxy group or groups or phenoxy
group or groups; or a C7-C20 aralkyloxy group which is
optionally substituted with a C1-C6 alkoxy group or groups

or phenoxy group or groups, and X1 to X4 is the same as defined above,
with a borohydride compound in the presence of an alcohol which
comprises adding the alcohol into a mixture of the halogen-substituted
terephthalic acid diester represented by the formula (1), the borohydride
compound and a solvent.
2. The method as claimed in claim 1, wherein R1 and R2 are the same
C1-C6 alkyl groups.
3. The method as claimed in claim 1 or 2, wherein all of X1 to X4 are
fluorine atoms.
4. The method as claimed in claim 1 or 2, wherein the amount of the
borohydride compound to be used is 2 to 2.5 moles relative to 1 mole
of the halogen-substituted terephthalic acid diester represented by the
formula (1).
5. The method as claimed in claim 1 or 2, wherein the borohydride
compound is an alkali metal borohydride.

6. The method as claimed in claim 5, wherein the alkali metal borohydride
is sodium borohydride.
7. The method as claimed in claim 1 or 2, wherein the alcohol is an
aliphatic alcohol.
8. The method as claimed in claim 7, wherein the aliphatic alcohol is
methanol.


A method for producing a halogen-substituted
benzenedimethanol represented by the formula (2):

wherein X1 to X4 are the same or different and
independently represent a halogen atom or the like,
provided that at least one of X1 to X4 is a halogen atom,
by reacting a halogen-substituted terephthalic acid diester
represented by the formula (1):

wherein R1 and R2 are the same or different and
independently represent a C1-C20 alkyl group which may have
a substitutent or substituents, and X1 to X4 is the same as
defined above.
with a borohydride compound in the presence of an alcohol
which comprises adding the alcohol into a mixture of the
halogen-substituted terephthalic acid diester represented
by the formula (1), the borohydride compound and a solvent.

Documents:

00462-kolnp-2007 correspondence-1.2.pdf

00462-kolnp-2007 correspondence-1.3.pdf

00462-kolnp-2007 others document.pdf

00462-kolnp-2007 p.a.pdf

00462-kolnp-2007-correspondence-1.1.pdf

00462-kolnp-2007-international search authority-1.1.pdf

00462-kolnp-2007-pct request form.pdf

00462-kolnp-2007-priority document-1.1.pdf

0462-kolnp-2007 abstract.pdf

0462-kolnp-2007 claims.pdf

0462-kolnp-2007 correspondence others.pdf

0462-kolnp-2007 description (complete).pdf

0462-kolnp-2007 form-1.pdf

0462-kolnp-2007 form-2.pdf

0462-kolnp-2007 form-3.pdf

0462-kolnp-2007 form-5.pdf

0462-kolnp-2007 international publication.pdf

0462-kolnp-2007 international search report.pdf

0462-kolnp-2007 pct form.pdf

0462-kolnp-2007 priority document.pdf

462-KOLNP-2007-ABSTRACT 1.1.pdf

462-KOLNP-2007-AMANDED CLAIMS.pdf

462-kolnp-2007-correspondence.pdf

462-KOLNP-2007-DESCRIPTION (COMPLETE) 1.1.pdf

462-KOLNP-2007-EXAMINATION REPORT REPLY RECIEVED.pdf

462-kolnp-2007-examination report.pdf

462-KOLNP-2007-FORM 1 1.1.pdf

462-kolnp-2007-form 18-1.1.pdf

462-kolnp-2007-form 18.pdf

462-KOLNP-2007-FORM 2 1.1.pdf

462-kolnp-2007-form 26.pdf

462-KOLNP-2007-FORM 3 1.1.pdf

462-kolnp-2007-form 3.pdf

462-kolnp-2007-form 5.pdf

462-KOLNP-2007-FORM-27.pdf

462-kolnp-2007-granted-abstract.pdf

462-kolnp-2007-granted-claims.pdf

462-kolnp-2007-granted-description (complete).pdf

462-kolnp-2007-granted-form 1.pdf

462-kolnp-2007-granted-form 2.pdf

462-kolnp-2007-granted-specification.pdf

462-KOLNP-2007-OTHERS 1.1.pdf

462-kolnp-2007-others.pdf

462-KOLNP-2007-PETITION UNDER RULE 137.pdf

462-kolnp-2007-reply to examination report.pdf

abstract-00462-kolnp-2007.jpg


Patent Number 247592
Indian Patent Application Number 462/KOLNP/2007
PG Journal Number 17/2011
Publication Date 29-Apr-2011
Grant Date 26-Apr-2011
Date of Filing 08-Feb-2007
Name of Patentee SUMITOMO CHEMICAL COMPANY LIMITED
Applicant Address 27-1, SHINKAWA 2-CHOME, CHUO-KU, TOKYO
Inventors:
# Inventor's Name Inventor's Address
1 KOJI HAGIYA 5-4-405, GAKUEN-CHO, IBARAKI-SHI, OSAKA
PCT International Classification Number C07C29/147,C07C33/46
PCT International Application Number PCT/JP2005/014486
PCT International Filing date 2005-08-02
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 2004-228954 2004-08-05 Japan