JPH11171799A - Production of biphenyl derivative having active substituent group - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially and advantageously produce the subject compound useful as an intermediate raw material for fine chemicals such as medicine or agrochemicals, a liquid crystal material, etc., by reacting a specific organomagnesium compound with an aryl compound in the presence of a copper salt. SOLUTION: An organomagensium compound represented by formula I [R is an aryl or a hydrocarbon which may have the aryl group; X is a halogen; (k) is 0 or 1] is reacted with an aryl compound represented by formula II [A is a halogen; Y is a leaving group; Z is an active substituent group; (m) is 0 or 1; (n) is an integer of 0-2] in the presence of a copper salt such as lithium copper(II) chloride to thereby industrially and advantageously produce the objective biphenyl derivative represented by the formula III [(k)+(m)] is 1}, useful as an intermediate raw material for fine chemicals such as medicines or agrochemicals or a liquid crystal material and having the active substituent group such as cyano group.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an industrially suitable method for producing a biphenyl derivative having an active substituent, which is useful as an intermediate material for fine chemicals such as medicines and agricultural chemicals and as a liquid crystal material.

[0002]

2. Description of the Related Art As one method for producing a biphenyl derivative having an active substituent such as a cyano group, a method of converting an existing inactive substituent into a desired active substituent is known. For example, a method of converting an oxazolinyl group into a cyano group by treating it with phosphorus oxychloride in pyridine [J. Me
d. Chem., Vol. 34, p. 2525 (1991)], a method of converting a butylcarbamoyl group into a cyano group by removing butanol [JP-A-7-53489], a method of converting a hydroxyiminomethyl group into a cyano group by dehydration [Europe Patent application publication (EP
A) No. 459136, Zh. Org. Khim. , Vol. 20, p. 1305 (1984
Year)], a method of reacting a chloroformyl group with an alcohol to form an alkoxycarbonyl group [J. Med. Chem. ,
34, 2525 (1991)], but all of these methods involve a large number of steps and discharge a large amount of metal hydroxide, which requires a lot of cost for disposal.
Industrial implementation involves difficulties. As a method for synthesizing cyanobiphenyls and alkoxycarbonylbiphenyls, a method has been reported in which halobenzonitrile or halobenzoic acid ester is dehalogenocoupled with bromobenzenes in the presence of triphenylphosphine and a reducing metal. However, in this method, it is necessary to use a large excess of zinc dust, for example, and this method is not necessarily industrially advantageous, for example, homocoupling occurs and the selectivity of the reaction is not sufficient. I can't say.

As a method for synthesizing cyanobiphenyls, alkoxycarbonylbiphenyls and acylbiphenyls, halobenzonitrile, halobenzoic acid ester or haloacetophenone can be prepared by using an organic metal compound in the presence of a palladium complex catalyst or a heavy metal such as manganese. Compounds, ie, arylboranes [European Patent Application Publication (EP
A) 690046], arylsilanes [JP-A-6-239770]
No.), aryl magnesium (JP-A-8-109143)
For example, a coupling method is known. However, these methods require expensive raw materials and special catalysts, or emit metal hydroxides that require a lot of disposal costs, and the yield is not always good.
It is not advantageous for industrial implementation. Furthermore, Diels-Alder
Methods for synthesizing cyanobiphenyls, alkoxycarbonylbiphenyls and acylbiphenyls for dehydrogenating the adduct obtained by the reaction are known, and examples thereof include cinnamonitrile, cinnamate or benzalacetone and N, Method by addition reaction with N-diethyl-1,3-butadiene [Bull. Inst. Chem. Res., Kyoto Uni
v. 60, 5-6, p. 336 (1982)]. A similar method for synthesizing cyanobiphenyls by an addition reaction between α-cyanocinnamic esters and butadiene [JP-A-9-87238] can be mentioned. However, all of these methods involve a large number of steps and have a low yield, which is not suitable for industrial practice.

As a method utilizing the Gomberg-Bachmann reaction, a method for synthesizing cyanobiphenyls or alkoxycarbonylbiphenyls by coupling an aryldiazonium salt with benzonitrile or benzoate [J. Am. Chem. Soc. , Vol. 46, p. 2339 (1924
)], And a method for synthesizing cyanobiphenyls in which alkylaniline (or cyanoaniline) is coupled as a diazonium salt with benzonitrile (or alkylbenzene) [Japanese Patent Application Laid-Open No. 50-13963]. However, in these reactions, three isomers are generated due to the difference in the coupling position, and the production rate of the desired cyanobiphenyls is low. Is difficult to separate.
A method using diazonium fluoride borate [J. Org. Chem. 49, p. 1594 (1984)]. However, this method also requires isolation of an aryldiazonium borofluorate which is unstable and difficult to handle, and requires expensive methods such as crown ethers. It is not suitable for industrial practice due to the use of a suitable phase transfer catalyst. Further, a method of Friedel-Craft reaction, such as a method of coupling biphenyl and acid chloride (Japanese Patent Application Laid-Open No. 54-16457), is known as a general method for synthesizing acyl biphenyls. It is necessary to use a stoichiometric amount of anhydrous aluminum chloride which is hygroscopic and highly corrosive, and this is not an advantageous method for industrial practice, such as discharging aluminum hydroxide which requires a lot of cost for disposal.

[0005]

SUMMARY OF THE INVENTION In view of the above, an object of the present invention is to provide an industrially advantageous method for producing a biphenyl derivative having an active substituent such as arylbenzonitrile.

[0006]

Means for Solving the Problems The inventors of the present invention have intensively studied for improvement, and as a result, by reacting an organomagnesium compound and an aryl compound in the presence of a copper salt, the objective biphenyl derivative having an active substituent is obtained. Was found to be obtained in a short process and in good yield, and the present invention was completed. That is, the present invention provides:

Embedded image And an organic magnesium compound represented by the general formula (II)

Embedded image With an aryl compound represented by the general formula (III), which is reacted in the presence of a copper salt.

[0007]

Embedded image Wherein R is an aryl group or a hydrocarbon group which may have an aryl group, X is a halogen atom, Y is a leaving group, Z represents an active substituent, and A represents a halogen atom. k
And m represent 0 or 1, but k + m = 1. n is 0
And n is 2, and when n is 2, A may be different. (2) The copper salt has the general formula [IV]

Embedded image (1) wherein M represents an alkali metal atom which may be different, and W represents a halogen atom which may be different. (3) The production method according to the above (1), wherein the copper salt is lithium copper (II) chloride, (4) the above (3), wherein k is 0, m is 1, Y is a halogen atom, and Z is a cyano group. And (5) k is 1, m is 0, Y is a halogen atom or a methoxy group, and Z is a cyano group.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The above general formulas [I] and [III]
In the formula, R represents an aryl group or a hydrocarbon group which may have an aryl group. Examples of the aryl group represented by R include a phenyl group having no substituent such as a phenyl group and a 1-naphthyl group or a naphthyl group, for example, 4-
Alkyl-substituted phenyl groups such as methylphenyl, 2-ethylphenyl and 3-isopropylphenyl, alkoxy-substituted phenyl groups such as 3-methoxyphenyl, and halogen-substituted phenyl groups such as 4-chlorophenyl, for example, 4-methyl-1-naphthyl group And a phenyl or naphthyl group having a substituent, such as an alkyl-substituted naphthyl group. Examples of the hydrocarbon group which may have an aryl group represented by R include methyl,
C _1-14 alkyl groups such as ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, such as benzyl ,
1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, C _7-10 phenyl-substituted alkyl group such as 4-phenylbutyl, such as vinyl, allyl, 2-methyl-2-propenyl, such as 4-pentenyl C _{2 -6} alkenyl group, for example styryl, C _8-10 phenyl-substituted alkenyl groups such as cinnamyl, such as ethynyl, C _2-6 alkynyl groups such as 1-propynyl, for example C _8, such as phenylethynyl, 3-phenyl-1-propynyl _{And a -10-} phenyl-substituted alkynyl group.

In the above general formula [I], X is a fluorine atom,
These are chlorine, bromine and iodine. In the above general formula [II], Y is a leaving group, for example, a halogen atom,
Examples thereof include an alkoxy group, an acyloxy group, an alkylsulfonyloxy group optionally having a halogen atom, and an arylsulfonyloxy group. The halogen atom represented by Y is, for example, fluorine, chlorine, bromine, iodine, etc., the alkoxy group is, for example, methoxy group, ethoxy group, propoxy group, etc., and the acyloxy group is, for example, acetoxy group, propionyloxy group. Examples of the alkylsulfonyloxy group optionally having a halogen atom include methanesulfonyloxy group and trifluoromethanesulfonyloxy group, and examples of the arylsulfonyloxy group include benzenesulfonyloxy group and paratoluenesulfonyloxy group. And the like. In the above general formulas [II] and [III], Z is an active substituent, and examples thereof include a cyano group, an alkoxycarbonyl group and an acyl group. The alkoxycarbonyl group represented by Z is, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, and the acyl group is, for example, an aliphatic group such as an acetyl group, a propionyl group, and a butyryl group. Examples of the acyl group include an aromatic acyl group such as a benzoyl group and a p-chlorobenzoyl group.

In the above general formulas [II] and [III], A is a halogen atom such as fluorine, chlorine, bromine and iodine. The present invention is carried out by reacting an organomagnesium compound represented by the general formula [I] and an aryl compound represented by the general formula [II] in the presence of a copper salt. Examples of the copper salt include copper (I) chloride, copper (I) bromide, copper (I) iodide, copper (II) fluoride, copper (II) chloride, copper (II) bromide, and copper (II) nitrate. ), Copper phosphate (I
General formulas [IV], such as inorganic acid copper salts such as copper sulfate (II) and potassium (II) chloride;

Embedded image Wherein M may be different, for example lithium,
W represents an alkali metal atom such as sodium and potassium, and W represents a halogen atom such as fluorine, chlorine, bromine and iodine which may be different. Inorganic copper complex salts represented by the following formulas: copper (II) formate, copper (II) acetate, copper (II) benzoate, copper (II) acetylacetonate, copper (II) benzoylacetonate, copper (II) ethyl acetoacetate ), For example, a complex of N, N, N ', N'-tetramethylethylenediamine and copper (II) chloride, bis (2,2'-bipyridine) copper (I) perchlorate Copper complex salts such as tetrakis (pyridine) copper (I) perchlorate, sodium dicarbonatocuprate (II), dichlorobis (pyridine N-oxide) copper (II), dichlorobis (triphenylphosphine oxide) copper (II) And so on.

The inorganic copper complex salt represented by the general formula [IV] is inexpensive, and when it is reacted in the presence thereof, the desired biphenyl derivative [III] having an active substituent can be obtained with a good yield. . Among them, lithium copper (II) chloride (Li ₂ CuC
When the reaction is carried out in the presence of l _4), obtained in the biphenyl derivative (III) is particularly high having an active substituent the desired product Osamu rate. These copper catalysts may be used alone or in combination with other copper salts. For example, lithium copper (II) chloride can be used in combination with an inorganic acid copper salt, an inorganic copper complex salt, an organic acid copper salt or an organic copper complex salt. When an inorganic or organic copper complex salt is used, the complex salt can be used after being formed in a reaction system. For example, lithium copper (II) chloride may be prepared in advance from lithium chloride and copper (II) by a known method [Synthesis, p. 303 (1971)] and added to the reaction system. Copper (I
Good results can be obtained even if I) is added separately to the reaction system and reacted. The amount of the copper salt to be used relative to the aryl compound (II) is usually 0.001 to 0.05, preferably 0.005 to 0.03 in molar ratio.
This is a much smaller amount of catalyst than the known methods using metals or metal salts other than copper. When the copper salt is not added, the yield of the target biphenyl derivative [III] having an active substituent is extremely low (see Reference Example 1 described later).

The charge ratio of the organomagnesium compound [I] to the aryl compound [II] is usually in the range of 0.90 to 3.00 moles, preferably 1.05 to 1.30 moles. m is 1
The aryl compound [II] is a known compound and can be generally obtained by halogenating the methyl group of the corresponding methyl biphenyl [see Reference Example 2 described later and European Patent Application Publication (EPA) 709369, No. 424317, UK Patent Application Publication (GB) 2225008]. Methyl biphenyls can be obtained, for example, by reacting toluidine with benzonitrile [Referential Example 3 to be described later and JP-A-9-19-1
No. 76104]. The aryl compound [II] wherein m is 0 can also be produced by a known method. If a typical example is 2-chlorobenzonitrile, for example,
J. Chem. Soc., P.1131 (1949), which can be obtained by reacting a diazonium salt of 2-chloroaniline with copper cyanide. In the method of the present invention,
When m is 1, when Y is a halogen atom and Z is a cyano group, and when m is 0, when Y is a halogen atom or a methoxy group and Z is a cyano group, Biphenyl derivative having a certain active substituent [III]
Is obtained with high purity and high yield.

The solvent used in the method of the present invention includes, for example, aliphatic hydrocarbons (eg, petroleum ether, pentane, hexane, heptane, cyclohexane, methylcyclohexane, etc.) and aromatic hydrocarbons (eg, benzene, toluene, xylene) Etc.), ethers (for example, methyl ether, ethyl ether, isopropyl ether, 1,2-dimethoxyethane, 2-methoxyethyl ether, tetrahydrofuran, 1,4-dioxane, etc.), or a mixture of these two types. Can be. The amount of the solvent used is usually the amount of 2 of the aryl compound [II].
It is 50 times by weight, preferably 3 to 20 times by weight. The method of the present invention is carried out by mixing a solution of the aryl compound [II] and a solution of the organomagnesium compound [I]. Generally, when the latter is dropped into the former under stirring, a good yield can be obtained. There are many. The reaction is usually performed using a batch type stirred tank type reactor, but a multi-stage continuous stirred tank type reactor can also be used. The dropwise addition of the organomagnesium compound [I] is usually carried out under cooling, usually at -50 to 50 ° C, preferably at 0 ° C.
It is performed at a temperature of 2020 ° C. The reaction is usually completed within 8 hours from the instant after dropping. After completion of the reaction, the reaction solution is poured into water or acidic water, and the organic layer is separated as it is, or extracted by adding a solvent such as toluene, ethyl acetate, ethyl ether, 1,2-dichloroethane, and the organic layer is concentrated. To obtain the product. If necessary, the product can be purified to a high purity by distillation, column chromatography or recrystallization.

[0014]

The present invention will be described in more detail with reference to the following examples and reference examples, but the present invention is not limited to these examples. Example 1 4'-bromomethylbiphenyl-4-carbonitrile 5
4.5 g (200 mmol) of dry tetrahydrofuran 20
Dissolved in 0.1 ml of lithium copper (II) chloride.
20.0 ml of a M tetrahydrofuran solution were added (molar ratio 0.01 / 4'-bromomethylbiphenyl-4-carbonitrile). While stirring the obtained solution under a nitrogen stream, 265 ml of a 0.90 M solution of butylmagnesium chloride in tetrahydrofuran was added thereto at a reaction temperature of 5 to 10 mL.
The solution was added dropwise over 15 minutes while maintaining the temperature. Thereafter, the reaction solution was heated to room temperature and left overnight. Ammonium chloride 12.9
g was dissolved in 200 ml of water, and the solution was added dropwise to the reaction solution while maintaining the internal temperature at room temperature. Further, 425 ml of toluene was added to the reaction solution to carry out liquid separation. The toluene layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 49.7 g of a product. This was distilled under reduced pressure to obtain 44.6 g of 4'-pentylbiphenyl-4-carbonitrile having a purity of 98.9% (high performance liquid chromatography) (yield: 89.5%). Boiling point 180-189 ° C / 1.0 mmHg IR νCN (NaCl, cm ^-1 ) 2227.1

Examples 2 to 20 Compounds [I] and [II] shown in Tables 1 and 2 and copper salts or copper complexes (molar ratio 0.01 / compound [II])
Was used to carry out a reaction in the same manner as in Example 1, and the product was purified by distillation or column chromatography to obtain a biphenyl derivative [III]. The results are shown in [Table 1] and [Table 2]. In Table 1 and Table 2, Me is a methyl group, Et is an ethyl group, Pr is a propyl group, Bu is a butyl group, Ph is a phenyl group, 4-ClPh is a 4-chlorophenyl group, and a is Lithium copper (II) chloride and b represent potassium copper (II) chloride, respectively.

[0016]

[Table 1]

[0017]

[Table 2]

Example 21 26.6 g (200 mmol) of 2-methoxybenzonitrile
Was dissolved in 200 ml of dry tetrahydrofuran, and 20 ml of a 0.1 M solution of lithium copper (II) chloride in tetrahydrofuran was added thereto (molar ratio: 0.01 / 2-methoxybenzonitrile). The resulting solution was stirred under a stream of nitrogen while adding 5.81 g (239 mmol) of magnesium and 405 mmol of p-bromotoluene in 265 ml of tetrahydrofuran.
9 g (239 mmol) of 4-methylphenylmagnesium bromide solution prepared by reacting
The solution was added dropwise over 15 minutes while maintaining the temperature at 0 ° C. Thereafter, the reaction solution was heated to room temperature and left overnight. Ammonium chloride 1
2.9 g was dissolved in 200 ml of water, and this was added dropwise to the reaction solution while maintaining the internal temperature at room temperature, and 425 ml of toluene was added to the reaction solution to carry out liquid separation. The toluene layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 38.0 g of a product.
This was distilled under reduced pressure to obtain 33.9 g of 4'-methylbiphenyl-2-carbonitrile having a purity of 99.5% (high performance liquid chromatography) (yield: 87.8%). Boiling point 155 to 156 ° C./5.0 mmHg IR νCN (KBr, cm ⁻¹ ) 2222.1

Example 22 27.5 g (200 mmol) of 4-chlorobenzonitrile was dissolved in 200 ml of dry tetrahydrofuran, and a 0.1 M solution of lithium copper (II) chloride in tetrahydrofuran was added.
0 ml were added (molar ratio 0.01 / 4-chlorobenzonitrile). The resulting solution was stirred under a stream of nitrogen while adding 5.8 mg of magnesium in 265 ml of tetrahydrofuran.
4 prepared by reacting 1 g (239 mmol) with 54.3 g (239 mmol) of 1-bromo-4-pentylbenzene.
A solution of -pentylphenylmagnesium bromide was added dropwise over 15 minutes while maintaining the reaction temperature at 5 to 10C. Thereafter, the reaction solution was heated to room temperature and left overnight. 12.9 g of ammonium chloride was dissolved in 200 ml of water, and the solution was added dropwise to the reaction solution while maintaining the internal temperature at room temperature.
Was added to the reaction solution to carry out liquid separation. The toluene layer that had been washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to give the product 48.9.
g was obtained. This was distilled under reduced pressure to obtain 42.6 g of 4'-pentylbiphenyl-4-carbonitrile having a purity of 99.1% (high performance liquid chromatography) (yield: 85.5).
%). Boiling point 180-189 ° C / 1.0 mmHg IR νCN (NaCl, cm ^-1 ) 2217.1

Examples 23 to 35 Reactions were carried out in the same manner as in Example 21 using the compounds [I] and [II] shown in Table 3 and copper salts or copper complexes (molar ratio 0.01 / compound [II]). And the product is purified by distillation or column chromatography to obtain the biphenyl derivative [II
I]. The results are shown in [Table 3]. In Table 3, Me is a methyl group, Et is an ethyl group, Pr is a propyl group,
a is lithium copper chloride (II), b is potassium copper chloride (I
I), MsO represents a methanesulfonyloxy group, TfO represents a trifluoromethanesulfonyloxy group, and TsO represents a paratoluenesulfonyloxy group.

[0021]

[Table 3]

Reference Example 1 4'-bromomethylbiphenyl-4-carbonitrile 5
4.5 g (200 mmol) of dry tetrahydrofuran 20
Then, 265 ml of a 0.90 M solution of butylmagnesium chloride in tetrahydrofuran was added dropwise thereto over 15 minutes while maintaining the reaction temperature at 5 to 10 ° C while stirring under a nitrogen stream. Thereafter, the temperature was raised to room temperature and left overnight.
12.9 g of ammonium chloride was dissolved in 200 ml of water, added dropwise to the reaction solution while keeping the internal temperature at room temperature, and 425 ml of toluene was added to the reaction solution to carry out liquid separation. The toluene layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 17.1 g of a product. This was distilled under reduced pressure to a purity of 85.
3.08 g of 8% (high performance liquid chromatography) 4'-pentylbiphenyl-4-carbonitrile was obtained (6.18% yield).

Reference Example 2 26.6 g (200 mmol) of 2-methoxybenzonitrile
Was dissolved in 200 ml of dry tetrahydrofuran, and stirred under a nitrogen stream while reacting with 5.81 g (239 mmol) of magnesium and 40.9 g (239 mmol) of p-bromotoluene in 265 ml of tetrahydrofuran. The bromide solution was added dropwise over 15 minutes while maintaining the reaction temperature at 5 to 10 ° C under cooling. Thereafter, the reaction solution was heated to room temperature and left overnight.
12.9 g of ammonium chloride was dissolved in 200 ml of water, and the solution was added dropwise to the reaction solution while keeping the internal temperature at room temperature, and 425 ml of toluene was added to the reaction solution to carry out liquid separation. The toluene layer washed with water and dehydrated with anhydrous magnesium sulfate was concentrated under reduced pressure to obtain 11.9 g of a product. This is distilled under reduced pressure to a purity of 7
2.02 g of 9.4% (high performance liquid chromatography) 4'-methylbiphenyl-2-carbonitrile was obtained (yield 5.24%).

Reference Example 3 200 g of 4'-methyl-4-cyanobiphenyl (1.0
3mol) in 2,000 g of 1,2-dichloroethane,
8.20 g of 2,2'-azobis (isobutyronitrile)
(50.0 mmol) was added. While stirring, add bromine 1
66 g (1.04 mol) were added at a reaction temperature of 80 ° C.
It was added dropwise in 40 minutes. Thereafter, the mixture was stirred at 80 ° C. for 5 hours,
Left at room temperature overnight. The reaction solution was transferred to a separating funnel, washed with water and separated. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 284 g of a product. This was recrystallized from toluene and hexane to give 4'-bromomethylbiphenyl- having a purity of 96.6% (high performance liquid chromatography).
183 g of 4-carbonitrile were obtained (yield 65.2).
%). Crystals having a purity of 99.4% (high performance liquid chromatography) obtained by recrystallizing it twice more with toluene and hexane had a melting point of 107.2 to 108.2 ° C. ¹ H-NMR (CDCl ₃ , δ ppm) 4.55 (s, 2H), 7.30
-7.80 (m, 8H).

Reference Example 4 97 g (1.1 mol) of isopentyl alcohol (3-methyl-1-butanol) and 83 g of sodium nitrite
(1.2 mol), 120 ml of concentrated hydrochloric acid was added dropwise over 60 minutes while maintaining the temperature at 0 to 5 ° C. with stirring. After stirring was continued for 10 minutes, the layers were separated, and the oil layer was washed with saturated aqueous sodium hydrogen carbonate to obtain a crude isopentyl nitrite product. Next, this was dissolved in 722 g (7 mol) of benzonitrile,
While maintaining the temperature at 5 to 70 ° C., the solution
-107 g (1.0 mol) of toluidine and benzonitrile 3
09 g (3 mol) of the mixture was added over 2 hours. Subsequently, distillation was carried out under reduced pressure, and after the benzonitrile was distilled off, the boiling point was 1
145 g of a 55-170 ° C./5 mmHg cut were obtained. The distillate was analyzed by gas chromatography to find that its components were 4'-methylbiphenyl-2-carbonitrile, 4 '
-Methylbiphenyl-3-carbonitrile and 4'-methylbiphenyl-4-carbonitrile, with contents of 48%, 12% and 24%, respectively (yield: 36
%, 9%, 18%). The fraction was further fractionated by a precision fractionator to separate the isomers. Each of the obtained isomer fractions (purity: 97% or more) was recrystallized from methanol to give 4'-methylbiphenyl-2-carbonitrile (A) and 4'-methylbiphenyl-3-carbon of [Table 4]. The nitrile (B) and 4'-methylbiphenyl-4-carbonitrile (C) were obtained.

[0026]

[Table 4]

[0027]

According to the method of the present invention, an organomagnesium compound and an aryl compound are reacted with a much smaller amount of a catalyst than in a known method using a metal or a metal salt other than copper, so that an objective compound can be obtained in a short step. Biphenyl derivatives having an active substituent can be obtained in good yield. Therefore, the method of the present invention is suitable as an industrial method for producing a biphenyl derivative having an active substituent.

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──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 69/76 C07C 69/76 A 253/30 253/30 255/50 255/50 // C07B 61/00 300 C07B 61/00 300

Claims (5)

[Claims] 1. A compound of the general formula [I] Wherein an organomagnesium compound represented by the general formula [II] is reacted with an aryl compound represented by the general formula [II] in the presence of a copper salt. A method for producing an aryl derivative having an active substituent represented by the formula: [In each formula, R represents an aryl group or a hydrocarbon group which may have an aryl group, X represents a halogen atom, Y represents a leaving group, Z represents an active substituent, and A represents a halogen atom. k
And m represent 0 or 1, but k + m = 1. n is 0
And n is 2, and when n is 2, A may be different. ] 2. A copper salt represented by the general formula [IV] The production method according to claim 1, which is an alkali metal salt represented by the formula: [In the formula, M represents an alkali metal atom which may be different, and W represents a halogen atom which may be different. ] 3. The method according to claim 1, wherein the copper salt is lithium copper (II) chloride. 4. The method according to claim 3, wherein k is 0, m is 1, Y is a halogen atom, and Z is a cyano group. 5. The method according to claim 3, wherein k is 1, m is 0, Y is a halogen atom or a methoxy group, and Z is a cyano group.