JP2000302697A - Production of biphenyl derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a biphenyl derivative useful as a liquid crystal raw material, an intermediate for pharmaceuticals and agrochemicals, or the like, in high reproducibility, purity and yield by reacting respectively specific arylboric acid (derivative) and aromatic compound under a specific condition. SOLUTION: The objective biphenyl derivative of formula IV can be produced by reacting an arylboric acid (derivative) expressed by formula I [R is H, a 1-6C alkyl, a (1-6C alkyl-substituted)phenyl, a 2-6C alkenyl, or the like; Y is OH, a 1-6C alkoxy, a group of formula II, or the like] such as phenylboric acid with an aromatic compound expressed by formula III (A is H, a 1-6C alkyl, phenyl, or the like; D is phenylene, naphthylene, or the like; X is chlorine, bromine, mesylate, or the like) such as chlorobenzene in the presence of a bivalent nickel complex such as dichlorobistriphenyl phosphine nickel(II), a base and an aromatic hydrocarbon solvent while adding water or an alcohol to the reaction system in an amount of 0.5-10 times mol based on the arylboric acid (derivative).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a biphenyl derivative useful as a liquid crystal raw material and an intermediate for medical and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, as a method for synthesizing a biaryl derivative using a boron compound, a method using a palladium or nickel complex as a catalyst is known. However, it is economically and industrially necessary to use a less expensive nickel complex catalyst. Preferred from a standpoint. Examples of the production method using a nickel complex catalyst include (A) a method in which an arylboronic acid and an aryl chloride are allowed to act in the presence of a divalent nickel complex and tripotassium phosphate anhydride (AF Indolese, Tetrahedron Lett)
ers, 38, 3513-3516 (1997)), (B) A method of reacting an aryl boronic acid with an aryl mesylate or an aryl arene sulfonate in the presence of a divalent nickel complex, zinc and tripotassium phosphate anhydrous (V. Percecet al, J. Or
g. Chem., 60, 1060-1065 (1995)), (C) A method in which an arylboronic acid and an aromatic chloride are allowed to act in the presence of a zero-valent nickel complex, a base, and an aprotic polar solvent (S. Sa)
ito et al, Tetrahedron Letters, 37, 2993-2996 (199
6), S. Saito et al, J. Org. Chem., 62,8024-8030 (199
7))), (D) A method of reacting an arylboronic acid or an arylboronic acid ester with an aryl halide or an arylfluoroalkylsulfonate in the presence of a zero-valent or divalent nickel complex, a base, and an aprotic polar solvent JP-A-2-131436, JP-A-Hei 3-2
No. 71243) is known.

The methods (A), (B), (C) and (D) are carried out under anhydrous conditions in order to prevent the nickel complex catalyst from being deactivated by moisture, so that special attention must be paid to the reaction operation. And it was complicated. Also, with these methods,
Variations in yield and poor reproducibility, as well as low production efficiency due to a low reaction rate (long-time reaction), have been major problems in industrial production. Moreover, in the above methods (A), (B), (C) and (D), arylboronic acids or arylboronic esters are used as the boron compound. There is also a drawback that it cannot be applied or that stable reaction results cannot be obtained even if it is applied. Also,
Arylboronic acids have poor storage stability and tend to become arylboronic anhydrides over time, and therefore have a large variation in reactivity and are difficult to handle.

[0004]

An object of the present invention is to obtain a biphenyl derivative from an arylboronic acid or a derivative thereof or an arylboronic anhydride in a short time with high reproducibility using a nickel complex as a catalyst. It is to provide a simple, convenient and industrially useful method.

[0005]

Means for Solving the Problems As a result of intensive studies on the above-mentioned problems, the present inventors have found that arylboronic acid or its derivative or arylboronic anhydride and an aromatic compound can be combined with a divalent nickel complex, a base, And the reaction in the presence of an aromatic hydrocarbon solvent, by adding only the optimal amount of water or alcohol, which has been the cause of the deactivation of the nickel catalyst, to obtain the biphenyl derivative in a surprisingly short time and with high yield. Have been obtained, and the present invention has been achieved.

That is, a first aspect of the present invention is the following general formula (I)

Embedded image (R is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having a phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonic acid ester group having a phenyl group which may have an alkyl group having 1 to 6 carbon atoms, fluorine, or 1 to 6 carbon atoms Of the fluoroalkyl group And, Y is a hydroxyl group, a carbon number 1 to 6
An phenoxy group, a cyclohexyloxy group which may have an alkyl group having 1 to 6 carbon atoms,

Embedded image (In each formula, q is 1, 2, 3 or 4, and r and s are each 2, 3, 4 or 5). ) Represented by the following general formula (II):

Embedded image (A is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having an optionally substituted phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonate group having a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, fluorine or an alkyl group having 1 to 6 carbon atoms Shows a fluoroalkyl group , D is shown phenylene, naphthylene, pyridine-diyl, quinolinediyl, pyrimidinediyl, triazinediyl, furandiyl, benzo furandiyl, shows a thiophenediyl or benzothiophene diyl, X is chlorine, bromine, iodine, a mesylate group, and arenesulfonate group. ) When the aromatic compound represented by the formula (1) is reacted in the presence of a divalent nickel complex, a base, and an aromatic hydrocarbon solvent, water or an alcohol is used in an amount of 0.5 to 10 moles per mol of the arylboronic acid or a derivative thereof. Wherein the compound represented by the following general formula (II)
I)

Embedded image (R, A, and D are the same as described above.)

A second aspect of the present invention is a compound represented by the following general formula (I)
V)

Embedded image (R is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having a phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonic acid ester group having a phenyl group which may have an alkyl group having 1 to 6 carbon atoms, fluorine, or 1 to 6 carbon atoms Of the fluoroalkyl group It is. ) And an arylboronic anhydride represented by the following general formula (II)

Embedded image (A is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having an optionally substituted phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonate group having a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, fluorine or an alkyl group having 1 to 6 carbon atoms Shows a fluoroalkyl group , D is shown phenylene, naphthylene, pyridine-diyl, quinolinediyl, pyrimidinediyl, triazinediyl, furandiyl, benzo furandiyl, shows a thiophenediyl or benzothiophene diyl, X is chlorine, bromine, iodine, a mesylate group, and arenesulfonate group. ) Is reacted in the presence of a divalent nickel complex, a base, and an aromatic hydrocarbon solvent, water or alcohol is added in an amount of 1 to 40 times the molar amount of the arylboronic acid or a derivative thereof. Having the following general formula (III):

Embedded image (R, A, and D are the same as described above.)

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. The general formula (I) used in the method of the present invention.
An arylboronic acid represented by or a derivative thereof, or
Examples of the arylboronic anhydride represented by the general formula (IV) include phenylboronic acid; alkyl-substituted phenylboronic acids such as p-methylphenylboronic acid and m-isopropylphenylboronic acid; p-isopropenylphenylboronic acid Alkenyl-substituted phenylboronic acids such as p-
Alkynyl-substituted phenylboronic acids such as ethynylphenylboronic acid; aryl-substituted boronic acids such as p-biphenylboronic acid; alkoxy-substituted phenylboronic acids such as m-methoxyphenylboronic acid and p-butoxyphenylboronic acid; p-methylthiophenylboron Alkylthio-substituted phenylboronic acids such as acids; cyano-substituted phenylboric acids; formyl-substituted phenylboric acids; acyl-substituted phenylboric acids such as p-acetylphenylboric acid; aroyl-substituted phenylboric acids such as p-benzoylphenylboric acid; p-methoxycarbonylphenyl Alkoxycarbonyl-substituted phenylboric acids such as boric acid; phenoxycarbonyl-substituted phenylboric acids such as p-methylphenoxycarbonylphenylboric acid; p-aminophenylboric acid, p-dimethyl p- carbamoylphenyl borate; amino-substituted phenylboronic acids such as amino boronic acid
Amido-substituted phenylboric acids such as p-monomethylcarbamoylphenylboric acid; sulfonyl-substituted phenylboric acids such as p-methylsulfonylphenylboric acid and p-tolylsulfonylphenylboric acid; fluorophenylboric acids; fluoro such as trifluoromethylphenylboronic acid Examples thereof include alkyl-substituted phenylboric acids and the like, esters thereof such as alkyl esters and phenyl esters, and acid anhydrides. These arylboronic acids or derivatives thereof may be used in combination of two or more.

The aromatic compound represented by the general formula (II), which is the other raw material used in the method of the present invention, includes, for example, when D is a phenylene group, halogen compounds such as chlorobenzene and p-bromotoluene. Benzenes; p
Halogenated benzenes such as chlorobenzaldehyde;
halogenated anisoles such as m-chloroanisole and p-chloro (2-methoxymethyl) benzene; halogenated benzonitrile such as o-chlorobenzonitrile and p-chlorobenzonitrile; methyl o-chlorobenzoate;
-Halogenated benzoic acid esters such as -methyl bromobenzoate; halogenated anilines such as p-chloroaniline, p-chloro-N, N-dimethylaniline; p-iodobenzoic acid amide; p-chloro-N, N- Halogenated benzoic acid amides such as dimethylbenzoic acid amide; halogenated acylbenzenes such as p-chloroacetophenone and p-bromobenzophenone, or 2,4-dimethoxy-5-
Examples thereof include halogenated benzenes having a plurality of substituents such as aminochlorobenzene.

In the general formula (II), D is phenylene;
A naphthylene, pyridinediyl, pyrimidinediyl, triazinediyl, quinolinediyl, furandiyl, benzofurandiyl, thiophendiyl or benzothiophendiyl group is shown, and the structural formula of the aromatic compound corresponding to each is the general formula (II-1) shown below. ) To (II-)
13). Preferred X is chlorine, bromine, iodine or the like, and preferred A is hydrogen, an alkyl group, an acyl group, an aroyl group, an alkoxy group, a cyano group, an aldehyde group, a carboxylic acid ester group, an amide group or an amino group. Is as shown in the above examples.

[0011]

Embedded image

The ratio of the arylboronic acid represented by the general formula (I) or a derivative thereof to the aromatic compound represented by the general formula (II) is usually determined from the viewpoint of economical efficiency and reactivity. Arylboronic acid or its derivative 0.8 to 1.5 per mole of the aromatic compound represented by II)
Mole, preferably 1 to 1.3 mole. In addition, the ratio of the arylboronic anhydride represented by the general formula (IV) and the aromatic compound represented by the general formula (II) is usually determined from the viewpoint of economy and reactivity. ) To 0.3 to 0.5 mol, preferably 0.33 to 0.4, of the arylboronic anhydride per 1 mol of the aromatic compound represented by the formula (1).
3 moles.

The aromatic hydrocarbon solvent used in the present invention includes, for example, benzene, toluene, xylene, mesitylene, ethylbenzene, n-propylbenzene and i-propylbenzene.
and so-propylbenzene. The amount used is not particularly limited, but is usually 700 to 3 parts by weight based on 100 parts by weight of the aromatic compound represented by the general formula (II).
About 2,000 parts by weight is industrially preferable from the viewpoint of operability and economy.

Various nickel phosphine complexes can be used as the divalent nickel complex catalyst. For example, dichlorobistriphenylphosphine nickel (II),
Dibromobistriphenylphosphine nickel (I
I), dichloro (1,2-bisdiphenylphosphinoethane) nickel (II), dichloro (1,2-bisdiphenylphosphinopropane) nickel (II), dichloro (1,2-bisdiphenylphosphinobutane) nickel (II), dichloro (1,1′-bisdiphenylphosphinoferrocene) nickel (II) and dichlorobistricyclohexylphosphine nickel (II). From the viewpoint of economy and reactivity, dichlorobistriphenylphosphine nickel (II) ), Dichloro (1,1′-bisdiphenylphosphinoferrocene) nickel (II) or dichlorobistricyclohexylphosphinenickel (II). From the viewpoints of economy and reactivity, the amount of the compound represented by the general formula (II)
0.005 to 1 mol of the aromatic compound represented by
0.1 mol, preferably 0.01 to 0.03 mol. Further, in order to prevent the catalyst from deteriorating and maintain the activity, a tertiary phosphine or a phosphite may be added in an amount of 1 to 5 times the mol of the nickel phosphine complex.

The base used in the present invention includes an alkali metal hydroxide or a salt thereof with a weak acid, an alkaline earth metal hydroxide or a salt thereof with a weak acid, and a quaternary ammonium hydroxide or a weak acid thereof. And the like. Preferred are sodium hydroxide, potassium hydroxide, sodium carbonate, cesium carbonate, tripotassium phosphate and tripotassium phosphate dihydrate. The amount used is 1 to 1 mole of the aromatic compound represented by the general formula (II).
５5 mol, preferably 1-3 mol.

The most important thing in the method of the present invention is that the aryl boric acid represented by the above general formula (I) or (IV) or a derivative thereof and the aromatic compound represented by the above general formula (II) are combined with 2 When reacting in the presence of a valent nickel complex, a base and an aromatic hydrocarbon solvent, a predetermined amount of water or alcohol is added.

Examples of alcohols include methanol, ethanol, n-propanol, iso-propanol,
n-butanol, iso-butanol, sec-butanol, tert-butanol and the like. Also,
Use of hydroalcoholic alcohol is not a problem.

The amount of water or alcohol to be added is
When the arylboronic acid or its derivative represented by the general formula (I) is used as a raw material, the amount is 0.5 to 10 mol, preferably 1 to 3 mol, per 1 mol of the arylboronic acid or its derivative. It is. When the arylboronic anhydride represented by the general formula (IV) is used as a raw material, the amount is 1 to 40 mol, preferably 3 to 30 mol, per 1 mol of the arylboronic anhydride. . In addition, water may be added using crystallization water contained in the base. If water or alcohol is not added or if the amount is less than the above-mentioned predetermined amount, the reaction rate is low, and if it is too large, the catalyst is deactivated, and satisfactory reaction results and reaction rates cannot be obtained.

The ratio of the arylboronic acid represented by the general formula (I) or a derivative thereof to the aromatic compound represented by the general formula (II) is usually from the viewpoint of economy and reactivity. Aromatic compound 1 represented by (II)
Arylboronic acid or its derivative 0.8 to mol
The amount is 1.5 mol, preferably 1 to 1.3 mol. Also,
Similarly, the ratio of the arylboronic anhydride represented by the general formula (IV) to the aromatic compound represented by the general formula (II) is the same as that of the aromatic compound represented by the general formula (II). Arylboronic anhydride 0.3 to 1 mol
It is 0.5 mol, preferably 0.33 to 0.43 mol.

In the method of the present invention, the reaction temperature is from 50 to 12
0 ° C, preferably 60 to 100 ° C. The reaction time varies depending on the reaction temperature, the amount of the catalyst and the like, but is usually 0.5 to 5
Hours, preferably 1 to 3 hours. The reaction is preferably performed in an inert gas atmosphere in order to prevent the catalyst from being deactivated by oxygen during the reaction. For example, nitrogen gas,
For example, argon gas. Although the reaction pressure is not particularly limited, it is usually carried out at atmospheric pressure.

Thus, the biphenyl derivative represented by the general formula (III), which is the target compound of the present invention, is obtained, but a purification operation may be performed to improve the purity of the biphenyl derivative. For example, after adding hydrochloric acid to the reaction solution and separating it into two layers, the layers are separated, washed with an aqueous sodium hydroxide solution, an aqueous sodium hypochlorite solution, a saturated saline solution, and the like, and then concentrated, crystallized, and crystallized. To obtain a highly purified product. The treatment may be performed with silica gel, alumina, or the like.

[0022]

EXAMPLES Hereinafter, the effects of the present invention will be described more specifically based on examples, but the present invention is not limited to the following examples.

EXAMPLE 1 0.15 g (0.22 mmol) of dichlorobistriphenylphosphine nickel (II) and 1.35 g (9.9 of p-methylphenylboronic acid) were placed in a 100 ml reactor.
3 mmol), 1.07 g of p-chlorobenzaldehyde
(7.64 mmol), tripotassium phosphate dihydrate3.
35 g (13.5 mmol) and 27 ml of toluene were charged and stirred at room temperature for 30 minutes. This was heated to 80 ° C. and reacted for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, and the reaction was stopped by adding 30 ml of water. Next, 7 ml of 2% hydrochloric acid was added thereto, followed by liquid separation. The obtained organic layer was analyzed by gas chromatography. The yield of 4-formyl-4'-methyl-1,1-biphenyl is p
-99% based on chlorobenzaldehyde.

Example 2 The same operation as in Example 1 was performed, except that 13.5 mmol of anhydrous tripotassium phosphate and 15 mmol of methanol were used instead of tripotassium phosphate dihydrate. The yield was 98% based on p-chlorobenzaldehyde.

Example 3 The same operation as in Example 1 was carried out except that 13.5 mmol of anhydrous tripotassium phosphate and 15 mmol of ethanol were used instead of tripotassium phosphate dihydrate. The yield was 99% based on p-chlorobenzaldehyde.

Comparative Example 1 The same operation as in Example 1 was carried out except that 13.5 mmol of anhydrous tripotassium phosphate was used instead of tripotassium phosphate dihydrate. The yield was 84% based on p-chlorobenzaldehyde.

Comparative Example 2 The same operation as in Example 1 was performed, except that water was added in an amount 13 times the molar amount of p-methylphenylboronic acid. The yield was 4% based on p-chlorobenzaldehyde.

Example 4 0.150 g (0.22 mmol) of dichlorobistriphenylphosphine nickel (II) and 1.07 g (7.6 g) of p-chlorobenzaldehyde were placed in a 100 ml reactor.
4 mmol), p-methylphenylboronic anhydride
17 g (3.31 mmol), tripotassium phosphate dihydrate 3.35 g (13.5 mmol), water 0.90 g (5
(0.00 mmol) and 27 ml of toluene and stirred at room temperature for 30 minutes. This was heated to 80 ° C. and reacted for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, and the reaction was stopped by adding 30 ml of water. Then, into this 2
After adding 7 ml of hydrochloric acid, liquid separation was performed. The obtained organic layer was analyzed by gas chromatography. 4-formyl-
The yield of 4'-methyl-1,1-biphenyl was 99% based on p-chlorobenzaldehyde.

Example 5 The same operation as in Example 4 was carried out except that 50 mmol of methanol was used instead of water. The yield was 97% based on p-chlorobenzaldehyde.

Example 6 The same operation as in Example 4 was performed except that 50 mmol of ethanol was used instead of water. The yield was 98% based on p-chlorobenzaldehyde.

Comparative Example 3 The same operation as in Example 4 was carried out except that 13.5 mmol of anhydrous tripotassium phosphate was used instead of tripotassium phosphate dihydrate and no water was added. The yield was 41% based on p-chlorobenzaldehyde.

Comparative Example 4 The same operation as in Example 4 was carried out except that water was added in an amount 45 times the molar amount of p-methylphenylboronic anhydride. The yield was 2% based on p-chlorobenzaldehyde.

Example 7 0.15 g (0.22 mmol) of dichlorobistriphenylphosphine nickel (II), 0.12 g (0.44 mmol) of triphenylphosphine, 1.09 g of m-chloroanisole in a 100 ml reactor (7.64
Mmol), 1.35 g of p-methylphenylboronic acid
(9.93 mmol), tripotassium phosphate dihydrate3.
35 g (13.5 mmol) and 27 ml of toluene were charged and stirred at room temperature for 30 minutes. Raise the temperature to 80 ° C and
Allowed to react for hours. After completion of the reaction, the mixture was cooled to room temperature, and the reaction was stopped by adding 30 ml of water. Next, 7 ml of 2% hydrochloric acid was added thereto, followed by liquid separation. The obtained organic layer was analyzed by gas chromatography. The yield of 3-methoxy-4'-methyl-1,1'-biphenyl is m
-99% based on chloroanisole.

Example 8 The same operation as in Example 7 was performed except that dichlorobistricyclohexylphosphine nickel (II) was used as a catalyst. The yield is 94% based on m-chloroanisole.
Met.

Example 9 The same operation as in Example 7 was carried out except that triphenylphosphine was added in an amount twice as much as that of nickel (II) dichlorobistriphenylphosphine as a catalyst. The yield was 99% based on m-chloroanisole.

Example 10 Dichloro (1,1′-bisdiphenylphosphinoferrocene) nickel (II) was used as a catalyst, and an equimolar amount of 1,1′-bisdiphenylphosphinoferrocene was added to the catalyst. Except for the above, the same operation as in Example 7 was performed. The yield was 73% based on m-chloroanisole.

Example 11 The same operation as in Example 7 was performed except that xylene was used instead of toluene as a solvent. The yield was 99% based on m-chloroanisole.

Example 12 The same operation as in Example 7 was carried out except that sodium hydroxide was used as the base instead of tripotassium phosphate dihydrate, and water was added in an amount twice as much as that of sodium hydroxide. Done. The yield was 88% based on m-chloroanisole.

Comparative Example 5 The same operation as in Example 7 was performed except that dimethoxyethane (DME) was used as a solvent. The yield was 7% based on m-chloroanisole.

Comparative Example 6 The same operation as in Example 7 was performed except that dimethylformamide (DMF) was used as a solvent. The yield is m-
It was 1% based on chloroanisole.

Example 13 A reaction between p-methylphenylboronic acid and o-chlorobenzonitrile was carried out in the same manner as in Example 1. 2-cyano-
The yield of 4′-methyl-1,1′-biphenyl was 99% based on o-chlorobenzonitrile.

Example 14 The reaction between p-methylphenylboronic acid and p-chlorobenzonitrile was carried out in the same manner as in Example 1. 4-cyano-
The yield of 4'-methyl-1,1'-biphenyl was 87% based on p-chlorobenzonitrile.

Example 15 A reaction between p-methylphenylboronic acid and methyl o-chlorobenzoate was carried out in the same manner as in Example 1. The yield of 2-methoxycarbonyl-4′-methyl-1,1′-biphenyl was 83% based on methyl o-chlorobenzoate.

Example 16 A reaction between p-methylphenylboronic acid and m-chloroanisole was carried out in the same manner as in Example 1. 3-methoxy-4 '
The yield of -methyl-1,1'-biphenyl was 99% based on m-chloroanisole.

Example 17 A reaction between p-methylphenylboronic acid and p-chloro (2-methoxymethoxy) benzene was carried out in the same manner as in Example 1. 4- (2-methoxymethoxy) -4′-methyl-
The yield of 1,1′-biphenyl was 74% based on p-chloro (2-methoxymethoxy) benzene.

Example 18 A reaction between p-methylphenylboronic acid and p-chloroaniline was carried out in the same manner as in Example 1. The 4-amino-4′-methyl-1,1′-biphenyl yield was 64% based on p-chloroaniline.

Example 19 In the same manner as in Example 1, the reaction between p-methylphenylboronic acid and p-chloro-N, N-dimethylaniline was carried out. 4
-(N, N-dimethylamino) -4'-methyl-1,
The yield of 1'-biphenyl was 64% based on p-chloro-N, N-dimethylaniline.

Example 20 As in Example 1, p-methylphenylboronic acid and 2,4
-Dimethoxy-5-aminochlorobenzene was reacted. The yield of 2,4-dimethoxy-5-amino-4'-methyl-1,1'-biphenyl is 2,4-dimethoxy-
It was 84% based on 5-aminochlorobenzene.

Example 21 A reaction between phenylboronic acid and p-chlorobenzonitrile was carried out in the same manner as in Example 1. The yield of 4-cyano-1,1'-biphenyl is 99% based on p-chlorobenzonitrile.
%Met.

Example 22 The reaction between phenylboronic acid and p-phenylsulfonechlorobenzene was carried out in the same manner as in Example 1. The yield of 4-phenylsulfone-1,1′-biphenyl was 68% based on p-phenylsulfonechlorobenzene.

Example 23 A reaction between p-methylphenylboronic acid and 2-chlorofuran was carried out in the same manner as in Example 1. The yield of p-tolyl-2-furan was 62% based on 2-chlorofuran.

Example 24 A reaction between p-methylphenylboronic acid and 2-chlorothiophene was carried out in the same manner as in Example 1. The yield of p-tolyl-2-thiophene was 86% based on 2-chlorothiophene.

Example 25 A reaction between p-methylphenylboronic acid and 3-chloropyridine was carried out in the same manner as in Example 1. The yield of p-tolyl-3-pyridine was 78% based on 3-chloropyridine.

[0054]

The effect of the present invention is to obtain a biphenyl derivative from an arylboronic acid or a derivative thereof or an arylboronic anhydride at a high reaction rate in a short time, with a high yield, and with good reproducibility, using a nickel complex as a catalyst. Another object of the present invention is to provide an economical, simple and industrially useful method.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 255/50 C07C 255/50 // C07B 61/00 300 C07B 61/00 300 (72) Inventor Kunio Mori 4F006 AA02 AC24 AC26 AD16 BA02 BA21 BA29 BA32 BA48 BA50 BB10 BC10 BC31 BC34 BC35 4H039 CA19 CG90 CG90

Claims (2)

[Claims] 1. A compound represented by the following general formula (I) (R is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having a phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonic acid ester group having a phenyl group which may have an alkyl group having 1 to 6 carbon atoms, fluorine, or 1 to 6 carbon atoms Of the fluoroalkyl group And, Y is a hydroxyl group, a carbon number 1 to 6
An alkoxy group, a phenoxy group optionally having an alkyl group having 1 to 6 carbon atoms, a cyclohexyloxy group, or a compound represented by the following general formula a, b, or c: (In each formula, q is 1, 2, 3 or 4, and r and s are each 2, 3, 4 or 5). ) And an arylboronic acid or a derivative thereof, and the following general formula (II): (A is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having an optionally substituted phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonate group having a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, fluorine or an alkyl group having 1 to 6 carbon atoms Shows a fluoroalkyl group , D is shown phenylene, naphthylene, pyridine-diyl, quinolinediyl, pyrimidinediyl, triazinediyl, furandiyl, benzo furandiyl, shows a thiophenediyl or benzothiophene diyl, X is chlorine, bromine, iodine, a mesylate group, and arenesulfonate group. ) When the aromatic compound represented by the formula (1) is reacted in the presence of a divalent nickel complex, a base, and an aromatic hydrocarbon solvent, the amount of water or alcohol is 0.5 to 10 moles per mole of the arylboronic acid or a derivative thereof. Wherein the following general formula (II)
I) (R, A, and D are the same as described above.) 2. The following general formula (IV): (R is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having a phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonic acid ester group having a phenyl group which may have an alkyl group having 1 to 6 carbon atoms, fluorine, or 1 to 6 carbon atoms Of the fluoroalkyl group It is. ) And an arylboronic anhydride represented by the following general formula (II): (A is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, 1 carbon atom
A phenyl group optionally having up to 6 alkyl groups, 2 carbon atoms
Alkenyl group having 6 to 6 carbon atoms, alkynyl group having 2 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms, alkylthio group having 1 to 6 carbon atoms, cyano group, formyl group, acyl group having 2 to 7 carbon atoms, carbon number A benzoyl group optionally having 1 to 6 alkyl groups, an alkoxycarbonyl group having 2 to 7 carbon atoms, a phenoxycarbonyl group optionally having 1 to 6 carbon atoms, and an alkyl having 1 to 6 carbon atoms Having an amino group which may have a group, an amide group which may have an alkyl group having 1 to 6 carbon atoms, a nitro group, an alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms. A sulfonyl group having an optionally substituted phenyl group, an alkyl group having 1 to 6 carbon atoms or a sulfonate group having a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, fluorine or an alkyl group having 1 to 6 carbon atoms Shows a fluoroalkyl group , D is shown phenylene, naphthylene, pyridine-diyl, quinolinediyl, pyrimidinediyl, triazinediyl, furandiyl, benzo furandiyl, shows a thiophenediyl or benzothiophene diyl, X is chlorine, bromine, iodine, a mesylate group, and arenesulfonate group. ) Is reacted in the presence of a divalent nickel complex, a base, and an aromatic hydrocarbon solvent, water or alcohol is added in an amount of 1 to 40 times the molar amount of the arylboronic acid or a derivative thereof. Having the following general formula (III): (Where R, A, and D are the same as described above).