JP2003300940A - Method for producing biaryl compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a biaryl compound having an electron-donating substituent, capable of simply producing the objective compound in a high yield in an industrially advantageous manner, by reacting a halogen-substituted aryl compound of which the aromatic ring has the electron- donating substituent and a halogen atom with an arylborane compound. <P>SOLUTION: This method for producing the biaryl compound having the electron-donating substituent comprises reacting the halogen-substituted aryl compound of which the aromatic ring has the electron-donating substituent and the halogen atom with an arylboronic acid, its derivative or dialkylarylborane in a solvent in the presence of an alkali hydrogen carbonate, a palladium catalyst insoluble in the solvent, and a phoshine. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a biaryl compound obtained by reacting a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring with an arylboronic acid, a derivative thereof or a dialkyl-arylborane. Regarding manufacturing method.

[0002]

2. Description of the Related Art Conventionally, a halogen-substituted aryl compound having at least a halogen atom in an aromatic ring in a solvent, in the presence of a base, and in the presence or absence of a ligand, using a palladium catalyst which is insoluble in a solvent such as palladium / carbon. To
The method for producing a biaryl compound by reacting with an arylboronic acid, a derivative thereof, or an arylborane compound such as dialkyl-arylborane is described in, for example, 1) Tetra.
hedron Letters, 35, 3277-32.
80 (1994), 2) Organic Letter
s, 10, 1555-1557 (2001) and the like. Since the palladium catalyst used as a catalyst in these methods is insoluble in the solvent, there is an advantage that the catalyst can be easily recovered after the reaction is completed.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have examined a method for producing a biaryl compound using the above-mentioned conventional solvent-insoluble palladium catalyst. As a result, when the halogen-substituted aryl compound having an electron-donating substituent on the aromatic ring was reacted with the arylborane compound, the desired biaryl compound could not be obtained in a satisfactory yield.

That is, according to the above conventional method 1), a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring in a solvent in the presence of sodium hydrogen carbonate and triphenylphosphine is used as an arylborane compound. When the reaction was carried out, the yield of the target biaryl compound was low and unsatisfactory as in the comparative example described later, and the result was that further improvement in yield was desired.

Further, in the above conventional method, the method 2) is
It is necessary to carry out the reaction in the absence of air, and the reaction time is as long as 24 hours, which is difficult to say as an industrial method.

An object of the present invention is to produce a biaryl compound by reacting a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring with an arylborane compound to produce a target product in high yield. An object of the present invention is to provide an industrially advantageous method that can be easily produced by.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems. As a result, in a solvent, in the presence of a base, a solvent-insoluble palladium catalyst and phosphine, a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring is reacted with an arylborane compound, and an alkali is used as a base. It was found that the yield of the target biaryl compound was remarkably improved when the metal hydrogen carbonate was used, and the present invention was completed.

That is, according to the present invention, a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring is converted into an arylboron in the presence of an alkali metal hydrogencarbonate, a solvent-insoluble palladium catalyst and phosphine in a solvent. It relates to a method for producing a biaryl compound having an electron-donating substituent, which comprises reacting with an acid, a derivative thereof, or a dialkyl-arylborane.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below. The halogen-substituted aryl compound having an electron-donating substituent and a halogen atom in the aromatic ring used in the present invention may be a monocyclic compound or a polycyclic compound, and as a ring-constituting atom. It may contain one or more heteroatoms selected from the group consisting of nitrogen atom, oxygen atom, sulfur atom and the like. Specific examples of the aromatic ring include benzene ring, naphthalene ring, anthracene ring, pyridine ring, quinoline ring, isoquinoline ring, indole ring, benzofuran ring and benzothiophene ring. Examples of the electron-donating substituent that the aromatic ring has include an amino group and an alkoxy group which may have an alkyl group at the nitrogen atom. Further, the halogen-substituted aryl compound can have a substituent inert to the reaction of the present invention on the aromatic ring. Examples of the substituent inert to the reaction of the present invention include:
Examples thereof include an alkyl group, an aryl group, an aralkyl group, an acylamino group, an alkoxycarbonylamino group and an arylsulfonylamino group.

Specific examples of the halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on the aromatic ring include, for example, general formula (1):

[0011]

[Chemical 4] (In the formula, X is CH or a nitrogen atom, Y is a halogen atom, R ¹ is an amino group or an alkoxy group which may have an alkyl group on the nitrogen atom, and R ² and R ³ are the same or Differently selected from the group consisting of a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, an aralkyl group, an alkoxy group or a nitrogen atom, which is an alkyl group, an acyl group, an alkoxycarbonyl group or an arylsulfonyl group. A compound which represents an amino group which may have a substituent, or R ² and R ³ may combine with two adjacent carbon atoms on the aromatic ring to form a ring). [Hereinafter, referred to as a halogen-substituted aryl compound (1). ] Is mentioned.

In the halogen-substituted aryl compound (1), the halogen atom represented by Y in the general formula (1) is specifically chlorine, bromine or iodine.

R ¹ in the general formula (1) is an amino group or an alkoxy group which may have an alkyl group. The amino group which may have an alkyl group is preferably one or two linear or branched alkyl groups having 1 to 6 carbon atoms.
And an amino group, which may have, specifically, an amino group, a (di) methylamino group (means a methylamino group and a dimethylamino group, and the same applies hereinafter), a (di) ethylamino group , (Di) n-propylamino group, (di) isopropylamino group, (di) n-butylamino group, (di)
Examples thereof include a tert-butylamino group, a (di) n-pentylamino group and a (di) n-hexylamino group, with an amino group being preferred. The alkoxy group is preferably an alkyloxy group having a linear or branched alkyl group having 1 to 6 carbon atoms, specifically, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group. , N-butoxy group, tert-butoxy group, n-pentyloxy group, n-hexyloxy group and the like can be exemplified, and have 1 to 4 carbon atoms.
The linear or branched alkyloxy group of is particularly preferable.

The alkyl group represented by R ² and R ³ includes, for example, a linear or branched alkyl group having 1 to 6 carbon atoms, specifically, a methyl group, an ethyl group, n
-Propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, n-pentyl group and n-
A hexyl group etc. can be illustrated. A preferred alkyl group is a linear or branched alkyl group having 1 to 4 carbon atoms, and a methyl group and an ethyl group are particularly preferred.

Examples of the alkenyl group represented by R ² and R ³ include linear or branched alkenyl groups having 2 to 6 carbon atoms, and specific examples thereof include ethenyl group and propenyl group. Group, butenyl group, pentenyl group and the like.

The alkynyl group represented by R ² and R ³ includes, for example, a linear or branched alkynyl group having 2 to 6 carbon atoms, specifically, an ethynyl group, a propynyl group, Examples thereof include a butynyl group and a pentynyl group.

Examples of the cycloalkyl group represented by R ² and R ³ include cycloalkyl having 4 to 6 carbon atoms, and specific examples thereof include a cyclobutyl group, a cyclohexyl group and a cyclopentyl group.

As the aryl group represented by R ² and R ³ , for example, a phenyl group which may have a substituent,
A monovalent residue of an aromatic compound which may have a nitrogen atom such as a naphthyl group, a pyridyl group, a quinolyl group and an isoquinolyl group as a constituent atom of an aromatic ring can be mentioned. Specifically, for example, the phenyl group which may have a substituent includes a phenyl group, an alkoxyphenyl group such as a methoxyphenyl group, a fluoroalkylphenyl group such as a trifluoromethylphenyl group and an acetylphenyl group. Examples thereof include an acylphenyl group, a cyanophenyl group and a nitrophenyl group.

Examples of the aralkyl group represented by R ² and R ³ include groups in which the hydrogen atom of the above alkyl group is substituted with the above aryl group, and examples thereof include a benzyl group, a methylbenzyl group and a phenethyl group. , Naphthylmethyl group, diphenylmethyl group and the like.

[0020] As the alkoxy group represented by R ² and R ³ is an alkyl group represented by R ² and R ^3, cycloalkyl group, an alkoxy group having an aryl group and aralkyl group. Preferably, it is an alkoxy group having a linear or branched alkyl group having 1 to 6 carbon atoms,
Specific examples include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a tert-butoxy group, an n-pentyloxy group and an n-hexyloxy group. Preferably, it is a linear or branched alkyloxy group having 1 to 4 carbon atoms.

In an amino group which may have at least one substituent selected from the group consisting of an alkyl group, an acyl group, an alkoxycarbonyl group and an arylsulfonyl group represented by R ² and R ³ on the nitrogen atom. As the alkyl group, those similar to the alkyl groups represented by R ² and R ³ can be mentioned. Examples of the acyl group include an alkylcarbonyl group and an arylcarbonyl group, and specifically, acetyl group, 2-ethylcarbonyl group, 3-propylcarbonyl group, 4-butylcarbonyl group, 5-pentylcarbonyl group, 6 -A straight-chain or branched alkylcarbonyl group having 2 to 7 carbon atoms such as a hexylcarbonyl group, a phenylcarbonyl group, a naphthylcarbonyl group and a substituent such as an alkyl group or an aralkyl group on the aromatic ring, which is 1 or 2 The aryl carbonyl group which has one can be illustrated. Examples of the alkoxy group in the alkoxycarbonyl group include those similar to the alkoxy groups represented by R ² and R ³ above. Specific examples of the alkoxycarbonyl group include methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonyl group, tert-butoxycarbonyl group, n-pentyloxycarbonyl group,
It is an alkyloxycarbonyl group having a linear or branched alkyl group having 1 to 6 carbon atoms such as n-hexyloxycarbonyl group. Examples of the aryl group in the arylsulfonyl group include those similar to the aryl groups represented by R ² and R ³ above. Preferred arylsulfonyl groups include substituents such as an alkyl group and an aralkyl group on the aromatic ring. The phenylsulfonyl group which may have 1 or 2 is mentioned.

The amino group which may have a substituent selected from the group consisting of an alkyl group, an acyl group, an alkoxycarbonyl group and an arylsulfonyl group on the nitrogen atom is specifically an amino group or (di) methyl. Amino group, (di) ethylamino group, (di) n-propylamino group, (di) isopropylamino group, (di) n-butylamino group,
(Di) tert-butylamino group, (di) n-pentylamino group, (di) n-hexylamino group and other alkylamino groups, acetylamino groups, 2-ethylcarbonylamino groups, 3-propylcarbonylamino groups, Alkylcarbonylamino group such as 4-butylcarbonylamino group, 5-pentylcarbonylamino group and 6-hexylcarbonylamino group, phenylcarbonylamino group, arylcarbonylamino group such as tolylcarbonylamino group and naphthylcarbonylamino group, methoxycarbonyl Amino group, ethoxycarbonylamino group, n-propoxycarbonylamino group, isopropoxycarbonylamino group,
Alkoxycarbonylamino groups such as n-butoxycarbonylamino group, tert-butoxycarbonylamino group, n-pentyloxycarbonylamino group and n-hexyloxycarbonylamino group, phenylsulfonylamino group, tosylamino group and N-methyl-N- An arylsulfonyl group such as a tosyl group can be exemplified.

When R ² and R ³ bond together with two adjacent carbon atoms on the aromatic ring to form a ring, the ring formed is preferably a 5-6 membered ring, The ring-constituting atom may be a carbon atom alone, or may include a carbon atom and a hetero atom such as an oxygen atom, a nitrogen atom and a sulfur atom. The ring formed by combining R ² and R ³ together with two adjacent carbon atoms on the aromatic ring may be a monocyclic ring or a condensed polycyclic ring, and these rings are aromatic rings. May or may not be. Further, the formed ring has the same alkyl group, aryl group, aralkyl group alkoxy group and acyl group as those described above, and a nitro group,
It may have one or more substituents selected from the group consisting of a cyano group and a fluoroalkyl group. When R ² and R ³ are bonded to each other with two adjacent carbon atoms on the aromatic ring to form a ring, a condensed ring is formed with the aromatic ring to which R ² and R ³ are bonded. Examples include a naphthalene ring, anthracene ring, indole ring, quinoline ring, isoquinoline ring, benzofuran ring, benzothiophene ring and the like.

Specific examples of the halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on the aromatic ring include 2-chloro-6-methylpyridine and 3-amino-2.
Examples thereof include, but are not limited to, -chloropyridine, 6-methoxy-2-chloropyridine, 3-amino-bromobenzene, and compounds in which a chlorine atom is replaced with a bromine atom or an iodine atom in these compounds.

In the arylboronic acid, its derivative or dialkyl-arylborane used in the present invention (hereinafter, these are generically referred to as arylborane compounds), the aromatic ring contained in the molecule is an electron in the above-mentioned aromatic ring. It is the same as that of the halogen-substituted aryl compound having a donative substituent and a halogen atom.

The arylboronic acid is an aromatic compound having at least one dihydroxyboryl group in the aromatic ring, and the arylboronic acid may form the following dehydration condensation product, for example.

[0027]

[Chemical 5] (In the formula, Ar represents an aryl group.)

Examples of the derivative of arylboronic acid include those in which at least one hydroxyl group of the dihydroxyboryl group of arylboronic acid is substituted with an alkoxy group.

Dialkyl-arylborane is an aromatic compound having at least one dialkylboryl group bonded to a carbon atom of an aromatic ring.

These arylborane compounds may have one or more substituents inert to the reaction of the present invention on the aromatic ring.

Specific examples of the arylborane compound include:
For example, general formula (2):

[0032]

[Chemical 6] (In the formula, Z represents CH or a nitrogen atom, and R ⁴ and R ⁵ are the same or different from each other and each is a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a nitro group, a cyano group, a carboxyl group, It represents an alkoxycarbonyl group, a carbamoyl group, a fluoroalkyl group or an acyl group, or R ⁴ and R ⁵ may be bonded together with two adjacent carbon atoms on the aromatic ring to form a ring, and
⁶ and R ⁷ are the same or different from each other and represent a hydroxyl group or an alkoxy group respectively, or R ⁶ and R ⁷ together form a divalent diol which forms a ring by combining with a boron atom by two oxygen atoms. When a residue is represented or Z represents a nitrogen atom, at least one of R ⁶ and R ⁷ may be an alkyl group. m is 1 or 2. ). The compound shown by these is mentioned.

In the substituents represented by R ⁴ and R ⁵ in the general formula (2), the alkyl group, aryl group, aralkyl group and alkoxy group are the same as those in the general formula (1) of the halogen-substituted aryl compound (1). Are the same as those represented by R ² and R ³ .

As the alkoxycarbonyl group represented by R ⁴ and R ⁵ , the hydroxyl group contained in the carboxyl group is converted into the same alkoxy group as described above, preferably a linear or branched alkyl group having 1 to 6 carbon atoms. Examples thereof include an alkoxycarbonyl group substituted with an oxy group, and specific examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an isopropoxycarbonyl group, an n-butoxycarbonyl group, a tert-butoxycarbonyl group, and an n-
Examples include a pentyloxycarbonyl group and an n-hexyloxycarbonyl group. Particularly preferred is an alkoxycarbonyl group in which the hydroxyl group of the carboxyl group is substituted with a linear or branched alkyloxy group having 1 to 4 carbon atoms.

Examples of the fluoroalkyl group represented by R ⁴ and R ⁵ include groups in which at least one hydrogen atom in the above alkyl group is substituted with a fluorine atom. Preferably, it is a methyl group or an ethyl group having 1 to 5 fluorine atoms, specifically, a monofluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 1-fluoroethyl group, 1,2-difluoromethyl group. Group, 1,1,2-trifluoroethyl group, 1,1,1,2-tetrafluoroethyl group, 1,1,2,2-tetrafluoroethyl group,
Examples include 1,1,1,2,2-pentafluoroethyl group and the like.

As the acyl group represented by R ⁴ and R ⁵ ,
Examples thereof include an alkylcarbonyl group and an arylcarbonyl group. The alkyl group contained in the alkylcarbonyl group is the same as the above alkyl group. Preferably, it is a linear or branched alkylcarbonyl group having 2 to 7 carbon atoms, for example, an acetyl group, a 2-ethylcarbonyl group,
3-propylcarbonyl group, 4-butylcarbonyl group,
Examples include 5-pentylcarbonyl group and 6-hexylcarbonyl group. The aryl group contained in the arylcarbonyl group is the same as the above aryl group. Preferred arylcarbonyl groups include a phenylcarbonyl group, a naphthylcarbonyl group, and those having one or two substituents selected from the group consisting of an alkyl group and an aralkyl group on the aromatic ring.

The divalent diol residue in which R ⁶ and R ⁷ together form a ring by combining with a boron atom through two oxygen atoms is a 5-membered ring or 6 together with the boron atom.
Those which form a member ring are preferable, and examples thereof include divalent groups derived from aliphatic and aromatic divalent alcohols such as ethylene glycol, propylene glycol, pinacol, neopentyl glycol and catechol.

Specific examples of the arylborane compound include:
Phenylboronic acid, 4-methylphenylborane compound,
4-methoxyphenylboronic acid, 4-acetylphenylborane compound, phenylenediboronic acid, diethyl (3-
Pyridyl) borane, 2-phenyl-1,3,2-benzodioxaborol, 2-phenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborol and the like can be mentioned. Not limited to.

In the present invention, the use ratio of the halogen-substituted aryl compound having an electron-donating substituent and a halogen atom in the aromatic ring and the arylborane compound is not particularly limited, but from the economical viewpoint, the former is the aromatic ring. The ratio of the latter boron atom is usually 1.0 to 4.0 mol, preferably 1.0 to 2.0, relative to 1 mol of the halogen atom in 1.
It is preferable to use it so that it becomes a mole.

As the phosphine used in the present invention, a wide variety of known phosphines that can be used as a complex ligand can be used. Specifically, triarylphosphines such as triphenylphosphine and tritoluylphosphine,
2- (ditert-butylphosphino) benzene, 2-
(Ditert-butylphosphino) biphenyl, 2-ditert-butylphosphino-2'-dimethylaminobiphenyl, 2-ditert-butylphosphino-2'-
Dialkyl-arylphosphines such as isopropyl biphenyl and 2-ditert-butylphosphino-2'-isopropylbinaphthyl, as well as 2- (dicyclohexylphosphino) benzene, 2- (dicyclohexylphosphino) biphenyl, 2- (diadamantylphosphino ) Biphenyl, 2-dicyclohexylphosphino-
2'-dimethylaminobiphenyl, 2-dicyclohexylphosphino-2'-isopropylbiphenyl, 2-
(Dicyclohexylphosphino) binaphthyl, 2-dicyclohexylphosphino-2'-isopropylbinaphthyl, 2- (2'-dicyclohexylphosphinophenyl) -2-methyl-1,3-dioxolane and 2-
(2'-dicyclohexylphosphinophenyl) -1,
Examples thereof include, but are not limited to, dicycloalkyl-arylphosphines such as 3-dioxolane.

The amount of phosphine used in the present invention is not particularly limited, but from the viewpoint of economic efficiency, it is based on 1 mol of the halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on the aromatic ring. 0.0001-
It is recommended to use 0.5 mol, preferably 0.001 to 0.05 mol.

In the present invention, an alkali metal hydrogencarbonate is used as a base in the reaction. By using the alkali metal hydrogencarbonate, the target biaryl compound can be produced in a higher yield than when other bases are used. Examples of the alkali metal hydrogencarbonate include potassium hydrogencarbonate and sodium hydrogencarbonate. The alkali metal hydrogencarbonate is usually used in an amount of 1 to 10 mol, preferably 2 to 5 mol, per 1 mol of the halogen-substituted aryl compound.

As the palladium catalyst which is insoluble in the solvent, any known palladium catalyst can be widely used as long as it is insoluble in the solvent, and metal palladium is preferably supported on the carrier.
Examples of the carrier supporting metallic palladium include silica, alumina, diatomaceous earth, activated clay, activated carbon, barium sulfate, calcium carbonate and the like. Among these carriers, activated carbon and alumina are preferable. Pd / carbon is activated carbon on which metallic palladium is supported,
Those containing 1 to 10% by weight of palladium metal are preferable. Pd / alumina is alumina in which metallic palladium is supported, and the palladium metal is 1 to 10% by weight.
Those containing are preferable. The amount of the solvent-insoluble palladium catalyst used in the present invention is such that the metal palladium contained in the catalyst is usually 0.1 to 1 mol of the halogen-substituted aryl compound having an electron-donating substituent and a halogen atom in the aromatic ring. It is preferable that the amount is 100 mmol, preferably 1 to 5 mmol.

The solvent that can be used in the reaction is, for example,
Examples thereof include water, ethers, amides, nitriles, ketones, alcohols and aromatic hydrocarbons, and these can be used alone or in combination of two or more.

The ethers include, for example, dimethoxyethane, tetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether, the amides include, for example, dimethylformamide and dimethylacetamide, and the nitriles include, for example. , Acetonitrile, propionitrile and the like, as the ketones, for example, acetone, ethyl methyl ketone and the like, as the alcohols, for example, methanol, ethanol,
n-propyl alcohol, isopropyl alcohol, n
-Butyl alcohol, tert-butyl alcohol, n
-Pentyl alcohol, n-hexyl alcohol, etc.
Examples of aromatic hydrocarbons include benzene, toluene and xylene.

Preferred solvents are water and a mixed solvent of water and an organic solvent, and more preferred solvents are water and a mixed solvent of water and an organic solvent miscible with water. The organic solvent miscible with water is selected from ethers, amides, nitriles, ketones, alcohols and the like, and it is particularly preferable to use a mixed solvent of water and alcohols. The alcohol used with water is preferably at least one linear aliphatic alcohol having 1 to 6 carbon atoms.

The amount of the solvent used is not particularly limited, but is usually 5 to 60 relative to 1 part by weight of a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on the aromatic ring.
It is preferable that the amount is 10 parts by weight, preferably 10 to 40 parts by weight.

When a mixed solvent of water and an organic solvent is used, water is usually used in an amount of about 0.1 to 30 parts by weight per 1 part by weight of a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring. The amount is preferably about 0.5 to 20 parts by weight, and the organic solvent is usually about 5 to 40 parts by weight, preferably 10 to 30 parts by weight.

In the present invention, an aldehyde such as an aliphatic aldehyde or an aromatic aldehyde can be further present in the reaction system.

In carrying out the method of the present invention, for example, a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom in an aromatic ring in a reactor, an arylborane compound, an alkali metal hydrogen carbonate, and a solvent-insoluble palladium compound. A catalyst, phosphine and solvent are charged in a predetermined amount and, with stirring, usually 50 to 150 ° C., preferably 75 to 10
Under heating at 0 ° C., usually for about 1 to 20 hours, preferably,
The reaction may be performed for about 2 to 10 hours.

When the reaction is carried out as described above, a halogen-substituted aryl compound having an electron-donating substituent and a halogen atom in the aromatic ring used in the reaction and a biaryl compound corresponding to the arylborane compound are obtained in high yield. . For example, by reacting the halogen-substituted aryl compound (1) with the arylborane compound (2) as described above, the general formula (3):

[0052]

[Chemical 7] (In the formula, X, Z, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and m are the same as described above).

From the reaction mixture after completion of the reaction of the present invention,
Known isolation and purification means such as filtration, extraction, concentration, distillation,
The target biaryl compound can be isolated by combining unit operations such as recrystallization and column chromatography.

[0054]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples.

Comparative Example 1 342 mg (2.66) of 3-amino-2-chloropyridine
), Phenylboronic acid 405 mg (2.66 mmol, pure content 80% by weight), triphenylphosphine 1
22 mg (0.47 mmol) were dissolved in 10 ml of 1,2-dimethoxyethane. 2.0 mol / l in the solution
5.0 ml of an aqueous sodium carbonate solution was added, and further 545 mg of 5% by weight Pd / carbon (water content 54% by weight) (metal palladium: 0.12 mmol) was added, and the mixture was heated and stirred at 80 ° C. for 8 hours for reaction. After completion of the reaction, the obtained reaction mixture was filtered, and the filter cake was washed 4 times with 20 ml of ethyl acetate. The filtrate and the washing liquid were combined, 30 ml of a 10 wt% potassium hydroxide aqueous solution was added and mixed, and the mixture was allowed to stand and then separated into an organic layer and an aqueous layer. The organic layer is 2 with 20 ml of saturated saline.
The extract was washed twice, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography [n-hexane: ethyl acetate = 1: 1 (volume ratio)] to obtain 89 mg (yield 20%) of 3-amino-2-phenylpyridine as a colorless solid. It was

Example 1 5.0 m of 2.0 mol / l potassium hydrogen carbonate was used in place of the 2.0 mol / l sodium carbonate aqueous solution in Comparative Example 1.
The same procedure as in Comparative Example 1 was carried out except that 1 was used. As a result, colorless solid 3-amino-2-phenylpyridine 20
0 mg (44% yield) was obtained.

Example 2 In Comparative Example 1, 5.0 m of 2.0 mol / l potassium hydrogen carbonate was used instead of the 2.0 mol / l sodium carbonate aqueous solution.
The same procedure as in Comparative Example 1 was carried out except that 1 was used, 10 ml of n-butanol was used instead of 1,2-dimethoxyethane, and the reaction time was changed to 9 hours. As a result, 412 mg of a colorless solid 3-amino-2-phenylpyridine (yield 9
1%) was obtained.

Comparative Example 2 382 mg of 2-chloro-6-methoxypyridine in place of 3-amino-2-chloropyridine in Comparative Example 1
(2.66 mmol) was used, the reaction time was changed to 7 hours, and the eluent for silica gel chromatography was changed to n-hexane: ethyl acetate = 10: 1 (volume ratio). It was As a result, a colorless oily substance 2
123 mg of -methoxy-6-phenylpyridine (yield 2
5%) was obtained.

Example 3 The same procedure as in Comparative Example 2 was carried out except that 5.0 ml of 2.0 mol / l potassium hydrogen carbonate aqueous solution was used in place of 2.0 mol / l sodium carbonate aqueous solution in Comparative Example 2. .
As a result, 252 mg (yield 42%) of 2-methoxy-6-phenylpyridine was obtained as a colorless oil.

Example 4 In Comparative Example 2, 5.0 ml of 2.0 mol / l potassium hydrogen carbonate aqueous solution was used instead of 2.0 mol / l sodium carbonate aqueous solution, and 1,2-dimethoxyethane was used instead. The same procedure as in Comparative Example 2 was repeated except that 10 ml of n-butanol was used and the reaction time was changed to 8 hours. As a result, 2-methoxy-6-phenylpyridine 2 which is a colorless oily substance
Obtained 49 mg (yield 50.5%).

Comparative Example 3 In place of 3-amino-2-chloropyridine in Comparative Example 1, 457 mg (2.66) of 3-amino-bromobenzene was used.
Comparative Example 1 except that the amount of 1,2-dimethoxyethane used was 15 ml, and the eluent for silica gel column chromatography was changed to n-hexane: ethyl acetate = 4: 1 (volume ratio). I went the same way. As a result, 80 mg of brown liquid 3-phenylaniline (yield 1
8%).

Example 5 The procedure of Comparative Example 3 was repeated except that 5.0 ml of 2.0 mol / l potassium hydrogen carbonate aqueous solution was used in place of 2.0 mol / l sodium carbonate aqueous solution. .
As a result, 306 mg of 3-phenylaniline as a brown liquid
(Yield 68%) was obtained.

Example 6 In Comparative Example 3, 5.0 ml of 2.0 mol / l potassium hydrogen carbonate aqueous solution was used instead of 2.0 mol / l sodium carbonate aqueous solution, and 1,2-dimethoxyethane was used instead. The same procedure as in Comparative Example 3 was carried out except that 10 ml of n-butanol was used. As a result, 356 mg (yield 80%) of 3-phenylaniline was obtained as a brown liquid.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4H006 AA02 AC24 BA25 BA48 BB11                       BB14 BB15 BB16 BB20 BB21                       BB31 BC10 BC19 BC31 BC32                       BC33 BC34 BC35 BE12                 4H039 CA41 CA42 CD20

Claims (5)

[Claims] 1. A halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring in the presence of an alkali metal hydrogen carbonate, a solvent-insoluble palladium catalyst and a phosphine in a solvent is converted to an arylboronic acid or a derivative thereof. Alternatively, a method for producing a biaryl compound having an electron-donating substituent, which comprises reacting with a dialkyl-arylborane. 2. A halogen-substituted aryl compound having an electron-donating substituent and a halogen atom on an aromatic ring is represented by the general formula (1): (In the formula, X is CH or a nitrogen atom, Y is a halogen atom, R ¹ is an amino group or an alkoxy group which may have an alkyl group on the nitrogen atom, R ² and R ³ are the same as each other, or Different from each other, hydrogen atom, alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group,
An aralkyl group, an alkoxy group, or an amino group which may have a substituent selected from the group consisting of an alkyl group, an acyl group, an alkoxycarbonyl group and an arylsulfonyl group at the nitrogen atom, or R ² and R ³ are Two adjacent carbon atoms on the aromatic ring may be bonded to each other to form a ring. ), Wherein arylboronic acid, its derivative or dialkyl-arylborane is represented by the general formula (2): (In the formula, Z represents CH or a nitrogen atom, and R ⁴ and R ⁵ are the same or different from each other and each is a hydrogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a nitro group, a cyano group, a carboxyl group, It represents an alkoxycarbonyl group, a carbamoyl group, a fluoroalkyl group or an acyl group, or R ⁴ and R ⁵ may be bonded together with two adjacent carbon atoms on the aromatic ring to form a ring, R
⁶ and R ⁷ are the same or different from each other and represent a hydroxyl group or an alkoxy group respectively, or R ⁶ and R ⁷ together form a divalent diol which forms a ring by combining with a boron atom through two oxygen atoms. When a residue is represented or Z represents a nitrogen atom, at least one of R ⁶ and R ⁷ may be an alkyl group. m is 1 or 2. ) Is a compound represented by the general formula (3): The method according to claim 1, which is a compound represented by the formula (X, Z, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and m are the same as the above). 3. The method according to claim 1, wherein the solvent-insoluble palladium catalyst is at least one selected from the group consisting of palladium / carbon and palladium / alumina. 4. The method according to claim 1, 2 or 3, wherein the solvent is a mixed solvent of water and at least one kind of linear aliphatic alcohol having 1 to 6 carbon atoms. 5. The method according to claim 1, wherein the reaction is carried out under heating at 50 to 150 ° C.