JPH10279551A - Production of 2-cyanobiphenyl compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To profitably, simply and industrially obtain the subject compound useful as an intermediate for medicines such as an oral hypotensive medicine by reacting a phenyl magnesium chloride compound with o-chlorobenzonitrile in an etheric organic solvent. SOLUTION: Thie method for producing a cyanobipheny compound comprises reacting 1 mole of o-chlorobenzonitrile with 1-3 moles, preferably 1-2 moles, of a compound of formula I (R<1> is a 1-6C alkyl, a 1-6C alkoxy, H) and with o-chlorobenzonitrile at a temperature of -40 deg.C to 50 deg.C, preferably -20 deg.C to 30 deg.C, usually in the atmosphere of an inactive gas such as nitrogen gas usually for 2-10 hr to obtain a compound of formula II. The reaction is carried out in a solvent obtained e.g. by adding manganese dioxide and trimethylchlorosilane respectively in amounts of 0.01-0.3 mole and 0.01-1 mole per mole of the o- chlorobenzonitrile to an etheric organic solvent such as tetrahydrofuran. The etheric organic solvent is used in an amount of >=100 pts.wt., preferably 200-2500 pts.wt., pre 100 pts.wt. of the o-chlorobenzonitrile.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a 2-cyanobiphenyl compound. More specifically, the present invention relates to a method for producing a 2-cyanobiphenyl compound useful as a pharmaceutical intermediate such as an oral hypotensive agent.

[0002]

2. Description of the Related Art Conventionally, as a method for producing a 2-cyanobiphenyl compound, there has been proposed a method in which (A) a phenylmagnesium halide compound and 2-halobenzonitrile are allowed to act in the presence of a manganese halide (JP-A-6-9536). JP-A-8-109143), and (B) a method in which a phenylmagnesium halide compound and 2-halobenzonitrile are allowed to act in the presence of metal manganese and trimethylchlorosilane.

[0003] However, the method (A) has a drawback that the handling thereof is complicated because the manganese halide has hygroscopicity.

In the method (B), metal manganese is used in an equimolar amount with respect to 2-halobenzonitrile. Therefore, it is necessary to treat metal manganese after the completion of the reaction.
Industrial waste is generated. Therefore, this method is not an industrially advantageous method.

As a method for producing 4'-methyl-2-cyanobiphenyl, which is a kind of 2-cyanobiphenyl compound, (C) a Ni catalyst is used in the presence of a zinc halide and an amine compound in the presence of 4-methyl. A method of producing 4′-methyl-2-cyanobiphenyl by reacting with phenylmagnesium halide and 2-halobenzonitrile (Japanese Patent Application Laid-Open No. 8-231454), and (D) a method of preparing phenylmagnesium halide and zinc halide. After the reaction, 4-bromobenzonitrile is allowed to act in the presence of a Ni catalyst to produce 4′-methyl-2-cyanobiphenyl (J. Org. Chem. 42. 1821, (1977)). Are known.

However, in the method (C), it is necessary to use an expensive tertiary amine as an amine compound in order to obtain a reaction yield of 80% or more. There are drawbacks.

Further, the method (D) has a disadvantage that it is inferior in economical efficiency, as in the method (C), because expensive bromide or iodine must be used as a halide for the reaction substrate.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of the above prior art, and has as its object to provide a method capable of economically, conveniently and industrially producing a 2-cyanobiphenyl compound. And

[0009]

That is, the gist of the present invention is as follows.
[1] After adding manganese dioxide and trimethylchlorosilane to an ether-based organic solvent, the compound represented by the general formula (I):

[0010]

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Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms or a hydrogen atom, and o-chlorobenzonitrile. General formula (II) characterized by the following:

[0012]

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Wherein R ¹ is as defined above, and a method for producing a 2-cyanobiphenyl compound represented by the following general formula (2):

[0014]

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(Wherein R ¹ represents an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms or a hydrogen atom) and ZnCl ₂ , Reacting the obtained reaction product with o-chlorobenzonitrile in the presence of a Ni-based catalyst and an aprotic polar solvent, a general formula (II):

[0016]

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(Wherein R ¹ is as defined above).

[0018]

According to the present invention, as described above, (1) manganese dioxide and trimethylchlorosilane are added to an ether-based organic solvent, and then the compound represented by the general formula (I) is added to the ether-based organic solvent. :

[0019]

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Wherein R ^{1 is} an alkyl group having 1 to 6 carbon atoms,
A phenylmagnesium chloride compound represented by an alkoxy group having 1 to 6 carbon atoms or a hydrogen atom) and o-
A method of reacting chlorobenzonitrile (hereinafter referred to as method I), or (2) a phenylmagnesium chloride compound represented by the general formula (I) and ZnCl ₂
And reacting the resulting reaction product with o-chlorobenzonitrile in the presence of a Ni-based catalyst and an aprotic polar solvent (hereinafter, referred to as Method II) by the general formula (II) ):

[0021]

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(Wherein R ¹ is the same as described above).

In each of the above methods I and II, a phenylmagnesium chloride compound represented by the general formula (I) is used as a starting material.

R ¹ is an alkyl group having 1 to 6 carbon atoms;
It is an alkoxy group having 1 to 6 carbon atoms or a hydrogen atom.

The alkyl group having 1 to 6 carbon atoms includes:
For example, a C1-C6 alkyl group which has a straight chain and a branched chain is mentioned. Specific examples of such an alkyl group having 1 to 6 carbon atoms include, for example, a methyl group, an ethyl group, an n-
Examples thereof include a propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, and a hexyl group. When R ¹ is a methyl group, 4′-methyl-2-cyanobiphenyl useful as an intermediate such as an oral antihypertensive agent is obtained.

Specific examples of the alkoxy group having 1 to 6 carbon atoms include, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert- Butoxy, pentyloxy, hexyloxy and the like.

Specific examples of the phenylmagnesium chloride compound represented by the general formula (I) include, for example,
Phenylmagnesium chloride; o-methylphenylmagnesium chloride, m-methylphenylmagnesium chloride, p-methylphenylmagnesium chloride;
o-ethylphenylmagnesium chloride, m-ethylphenylmagnesium chloride, p-ethylphenylmagnesium chloride; on-propylphenylmagnesium chloride, mn-propylphenylmagnesium chloride, pn-propylphenylmagnesium chloride, o- Isopropylphenylmagnesium chloride, m-isopropylphenylmagnesium chloride,
p-isopropylphenylmagnesium chloride; o-
n-butylphenylmagnesium chloride, mn-butylphenylmagnesium chloride, pn-butylphenylmagnesium chloride, o-isobutylphenylmagnesium chloride, m-isobutylphenylmagnesium chloride, p-isobutylphenylmagnesium chloride, o-sec- Butylphenylmagnesium chloride, m-sec-butylphenylmagnesium chloride, p-sec-butylphenylmagnesium chloride, o-tert-butylphenylmagnesium chloride, m-tert-butylphenylmagnesium chloride, p-tert-butylphenylmagnesium chloride; o-pentylphenyl magnesium chloride, m-
Pentylphenyl magnesium chloride, p-pentylphenyl magnesium chloride; o-hexylphenyl magnesium chloride, m-hexylphenyl magnesium chloride, p-hexylphenyl magnesium chloride; o-methoxyphenyl magnesium chloride, m
-Methoxyphenylmagnesium chloride, p-methoxyphenylmagnesium chloride; o-ethoxyphenylmagnesium chloride, m-ethoxyphenylmagnesium chloride, p-ethoxyphenylmagnesium chloride; on-propoxyphenylmagnesium chloride, mn-propoxyphenylmagnesium Chloride, pn-propoxyphenylmagnesium chloride, o-isopropoxyphenylmagnesium chloride, m-isopropoxyphenylmagnesium chloride, p-isopropoxyphenylmagnesium chloride; on-butoxyphenylmagnesium chloride,
mn-butoxyphenylmagnesium chloride, p-
n-butoxyphenylmagnesium chloride, o-isobutoxyphenylmagnesium chloride, m-isobutoxyphenylmagnesium chloride, p-isobutoxyphenylmagnesium chloride, o-sec-butoxyphenylmagnesium chloride, m-sec-butoxyphenylmagnesium chloride, p -Sec-butoxyphenylmagnesium chloride, o-tert-butoxyphenylmagnesium chloride, m-tert-butoxyphenylmagnesium chloride, p-tert-butoxyphenylmagnesium chloride; o-pentyloxyphenylmagnesium chloride, m-pentyloxyphenylmagnesium chloride , P-pentyloxyphenylmagnesium chloride; o-hexyloxyphenylmagnesium Chloride, m- hexyloxy phenyl magnesium chloride, etc. p- hexyloxy phenyl magnesium chloride. Among the phenylmagnesium chloride compounds, when the p-methylphenylmagnesium chloride is used, 4′-methyl- is useful as an intermediate such as an oral antihypertensive.
Since 2-cyanobiphenyl is obtained, the p-methylphenylmagnesium chloride can be used particularly preferably.

In each of the methods I and II, a phenylmagnesium chloride compound represented by the general formula (I) is used as a starting material, and a 2-cyanobiphenyl compound represented by the general formula (II) is obtained as a target compound. Can be

First, the method I will be described.

In the method I, first, manganese dioxide and trimethylchlorosilane are added to an ether solvent.

The ether organic solvent is an ether alone or a mixed solvent of the ether and another organic solvent. In the present invention, the ether organic solvent is preferably substantially an ether, and the other organic solvent can be used in an amount that does not impair the purpose of the present invention.

Examples of the ether include tetrahydrofuran, diisopropyl ether, tert-butyl methyl ether and the like. These ethers can be used alone or in combination of two or more. Among the above-mentioned ethers, tetrahydrofuran can be suitably used.

As the other organic solvent, an organic solvent which does not react with the phenylmagnesium chloride compound can be used. Specific examples of such other organic solvents include, for example, organic solvents that do not react with Grignard reagents represented by aromatic hydrocarbons such as toluene and xylene.

The amount of the ether organic solvent used is 1 to 100 parts by weight of o-chlorobenzonitrile described later.
It is desirably at least 00 parts by weight, preferably 200 to 2500 parts by weight.

One feature of the method I is that manganese dioxide is used. The manganese dioxide has the advantage of low hygroscopicity and easy handling.

The amount of the manganese dioxide to be used may be generally a catalytic amount with respect to o-chlorobenzonitrile described later. That is, the amount of the manganese dioxide used is usually 0.01 to 1 mol of o-chlorobenzonitrile.
-0.3 mol, preferably 0.02-0.2 mol is desirable from the viewpoint of economy and reactivity.

The amount of the trimethylchlorosilane used is as follows:
Usually, 0.0 to 1 mol of o-chlorobenzonitrile is used.
From 1 to 1 mol, preferably from 0.02 to 0.5 mol is desirable from the viewpoint of economy and reactivity.

After adding manganese dioxide and trimethylchlorosilane to the ether-based organic solvent, the phenylmagnesium chloride compound represented by the general formula (I) is reacted with o-chlorobenzonitrile in the ether-based organic solvent. .

The amount of the phenylmagnesium chloride compound to be used is 1 to 3 mol, preferably 1 to 2 mol, per 1 mol of o-chlorobenzonitrile, from the viewpoint of economy and reactivity.

The reaction temperature at the time of reacting the phenylmagnesium chloride compound with o-chlorobenzonitrile is desirably -40 ° C or higher, preferably -20 ° C or higher, and 50 ° C or lower, preferably 30 ° C or lower. Below, it is more desirable that it is 10 ° C or less.

The atmosphere for the reaction is not particularly limited. Usually, the atmosphere is preferably an inert gas atmosphere such as a nitrogen gas.

The reaction time varies depending on the reaction temperature and the like, and cannot be unconditionally determined.
It is about 0 hours.

Thus, a 2-cyanobiphenyl compound represented by the general formula (II), which is the target compound of the present invention, is obtained.

After completion of the reaction, the above-mentioned 2-cyanobiphenyl compound can be isolated by usual operations such as filtration, washing, extraction, concentration, distillation, crystallization and the like.

Next, the method II will be described.

In the method II, the phenylmagnesium chloride compound represented by the general formula (I) and ZnC
After reacting l _2, and a reaction product obtained and o- chlorobenzonitrile in the reaction in the presence of a Ni-based catalyst, the presence of inexpensive aprotic polar solvents, surprisingly In particular, 2 represented by the general formula (II)
-An excellent effect that a cyanobiphenyl compound can be obtained very efficiently is exhibited.

In the method II, first, the phenylmagnesium chloride compound represented by the general formula (I) is reacted with ZnCl ₂ .

In reacting the phenylmagnesium chloride compound with ZnCl ₂ , an ether organic solvent can be used as a solvent.

Examples of the ether-based organic solvent include those similar to those used in the method I.

The amount of the ether-based organic solvent to be used is not particularly limited, but is usually preferably about 100 to 1,000 parts by weight based on 100 parts by weight of the phenylmagnesium chloride compound.

The phenylmagnesium chloride compound may be dissolved in the ether organic solvent in advance.

The mixing ratio of the phenylmagnesium chloride compound and ZnCl ₂ is usually from about 0.9 to 1.2 mol of ZnCl ₂ per mol of the phenylmagnesium chloride compound from the viewpoint of economy and reactivity. Should be fine.

The atmosphere for the reaction between the phenylmagnesium chloride compound and ZnCl ₂ is usually preferably an inert gas such as nitrogen gas or argon gas. Further, the pressure of the atmosphere is not particularly limited, and may be generally atmospheric pressure.

The reaction temperature may usually be about 0 to 70 ° C.

The reaction time varies depending on the reaction temperature and cannot be determined unconditionally.
It should be about an hour.

After the completion of the reaction, in the method (II), the reaction solution can be subjected to the reaction with o-chlorobenzonitrile without removing the reaction product from the reaction solution.

One major feature of the present invention in the reaction of the reaction product with o-chlorobenzonitrile is that an aprotic polar solvent is used.

In the method (II), the aprotic polar solvent is used. Such an aprotic polar solvent is a compound which is very inexpensive and can be easily obtained. In the case where is used, there is an advantage that the 2-cyanobiphenyl compound which is the target compound of the present invention can be obtained in a high yield.

Examples of the aprotic polar solvent include dimethylformamide, dimethylacetamide, N
-Methyl-2-pyrrolidone, dimethylsulfoxide and the like.

The amount of the aprotic polar solvent used is usually from 0.1 to 3 mol, preferably from 0.5 to 2 mol, per mol of o-chlorobenzonitrile, from the viewpoint of reaction yield and economy. Desirably it is molar.

In the reaction between the reaction product and o-chlorobenzonitrile, a Ni-based catalyst is used in the present invention.

Examples of the Ni-based catalyst include dichlorobis (triphenylphosphine) nickel (II) and dibromobis (triphenylphosphine) nickel (II).
And so on.

The amount of the Ni-based catalyst used is usually 0.01 to 0.3 mol, preferably 0.02 to 0.2 mol, per 1 mol of o-chlorobenzonitrile.

In this case, the amount of the ether organic solvent to be used is not particularly limited, but is usually at least 100 parts by weight, preferably about 200 to 2500 parts by weight, per 100 parts by weight of the o-chlorobenzonitrile. Is preferred.

In addition to the o-chlorobenzonitrile, the aprotic polar solvent and the Ni-based catalyst also
It can be previously dissolved in the ether organic solvent.

Usually, the reaction between the reaction product and o-chlorobenzonitrile is carried out, for example, by dissolving o-chlorobenzonitrile, the aprotic polar solvent and the Ni-based catalyst in the ether-based organic solvent. A reaction solution containing the reaction product can be dropped into such a solution.

In this case, the quantitative ratio of the reaction product to o-chlorobenzonitrile is usually 1 mole of o-chlorobenzonitrile, and the phenylmagnesium chloride compound 1 to 1 which is the raw material of the reaction product is used. It may be 3 moles, especially about 1 to 2 moles.

The atmosphere during the reaction is usually preferably an inert gas such as nitrogen gas or argon gas. Further, the pressure of the atmosphere is not particularly limited, and may be generally atmospheric pressure.

The reaction temperature is usually -5 ° C. or higher, preferably 20 ° C. or higher, more preferably 40 ° C. or higher, and 80 ° C. or lower, preferably 60 ° C. or lower.
It is desirable that:

The reaction time varies depending on the reaction temperature and cannot be unconditionally determined.
It should be about an hour.

Thus, a 2-cyanobiphenyl compound represented by the general formula (II), which is the target compound of the present invention, is obtained. To improve the purity of the 2-cyanobiphenyl compound, for example, aqueous hydrochloric acid or the like is used. After separation using, for example, washing with a saline solution or the like, the resulting organic layer may be distilled off, and purified by distillation. Further, by treating the 2-cyanobiphenyl compound purified by distillation with, for example, activated carbon, silica gel, alumina, or the like, a compound having higher purity can be isolated.

Thus, the 2-cyanobiphenyl compounds obtained by the methods I and II can be suitably used as a pharmaceutical intermediate such as an oral hypotensive agent.

[0073]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to only these examples.

Example 1 In a 1-liter flask, manganese dioxide 2.09 was added.
g (0.024 mol), trimethylchlorosilane10.
4 g (0.096 mol) and tetrahydrofuran 20
6 g was charged and stirred at 40 to 45 ° C. for 3 hours. Thereafter, 41.3 g of o-chlorobenzonitrile (0.
3 mol) and cooled to 0-5 ° C.

Next, a tetrahydrofuran solution of p-methylphenylmagnesium chloride was placed in the flask.
Then, 00 g (concentration of p-methylphenylmagnesium chloride: 19.8% by weight, content of p-methylphenylmagnesium chloride: 0.525 mol) was added dropwise at 0 to 5 ° C over 6 hours, and the mixture was kept warm for 1 hour. And reacted.

After the completion of the reaction, 100 ml of 12% by weight hydrochloric acid was poured into the flask, allowed to stand for 30 minutes, separated, and the separated organic layer was washed with 100 ml of 15% by weight saline.

Next, the solvent in the obtained organic layer was distilled off, and 73.1 g of crude 4′-methyl-2-cyanobiphenyl was distilled off.
(0.249 mol).

The obtained crude 4'-methyl-2-cyanobiphenyl was subjected to analysis (HPLC analysis) using high performance liquid chromatography, and it was found that 4'-methyl-2-cyanobiphenyl was obtained.
The purity of cyanobiphenyl was 65.9% by weight, and the reaction yield was 83.1 mol%.

Next, the obtained crude 4'-methyl-2-
When 73.1 g of cyanobiphenyl was purified by distillation, 40.2 g of 4'-methyl-2-cyanobiphenyl having a purity of 98.4% by weight was obtained.

Furthermore, 4 ′ obtained by purification by distillation
40.2 g of -methyl-2-cyanobiphenyl are recrystallized in 200 g of n-heptane to give a purity of 99.
2% by weight of 4'-methyl-2-cyanobiphenyl
2 g were obtained.

It was confirmed by the following physical properties that the obtained compound was 4'-methyl-2-cyanobiphenyl.

(1) Melting point: 52.1-53.2 ° C. (2) ¹ H-NMR (DMSO-d ₆ ) δ (ppm): 7.95
(D, 1H, J = 8 Hz), 7.78 (t, 1H, J =
8Hz), 7.69-7.32 (m, 6H), 2.39
(S, 3H)

Example 2 First, ZnCl ₂ 65. was placed in a 1-liter flask.
4 g (0.48 mol) and tetrahydrofuran 325
g, and 360 g of a solution of p-methylphenylmagnesium chloride in tetrahydrofuran (concentration of p-methylphenylmagnesium chloride: 20.1% by weight, content of p-methylphenylmagnesium chloride: 0.48 mol) was added to 30 to 30 g. After dropwise addition at 40 ° C. over 30 minutes, the mixture was kept warm for 1 hour to obtain a slurry of a p-methylphenylzinc compound in tetrahydrofuran.

On the other hand, separately, 7.85 g (0.012 mol) of dichlorobis (triphenylphosphine) nickel (II) as a Ni catalyst and dimethylacetamide 41 as an aprotic polar solvent were placed in a 2 liter flask. 4.8 g (0.48 mol), 206 g of tetrahydrofuran and 41.3 g (0.3 mol) of o-chlorobenzonitrile as an ether solvent were charged, and 45 to 50 were charged.
Warmed to ° C.

Next, the above-prepared slurry of the p-methylphenylzinc compound in tetrahydrofuran was dropped into the 2 liter flask at 45 to 50 ° C. over 3 hours. Done.

After completion of the reaction, 3% by weight
400 ml of aqueous hydrochloric acid was injected, left standing for 30 minutes, and then separated, and the separated organic layer was washed with 400 ml of 15% by weight saline.

Next, the solvent of the obtained organic layer was distilled off to obtain 70.8 g of crude 4′-methyl-2-cyanobiphenyl.

When the obtained crude 4′-methyl-2-cyanobiphenyl was subjected to HPLC analysis, the purity of 4′-methyl-2-cyanobiphenyl was 69.5% by weight, and the reaction yield was: 84.9 mol%.

Next, the obtained crude 4'-methyl-2-
When 70.8 g of cyanobiphenyl was purified by distillation, 41.5 g of 4'-methyl-2-cyanobiphenyl having a purity of 97.5% by weight was obtained.

Next, 4'-methyl-purified by distillation
41.5 g of 2-cyanobiphenyl was added to n-heptane 200
g, and add 2 g of alumina.
Heated and stirred for minutes.

Thereafter, the alumina was separated by filtration, and crystals were precipitated by cooling. After filtration, the crystals were washed with n-heptane, and 36.0 g of 49.8 g of 4'-methyl-2-cyanobiphenyl having a purity of 99.8% by weight was obtained. Obtained. 4'-methyl-2 obtained
-The melting point of cyanobiphenyl was 52.9-53.5 <0> C.

Example 3 In Example 1, 280 g of a solution of p-methylphenylmagnesium chloride in tetrahydrofuran [concentration: 2
0.2% by weight, 0.375 mol] was added dropwise at −35 to −30 ° C. over 5 hours, and the reaction was performed in the same manner as in Example 1. The obtained reaction solution was separated. The separated organic layer was washed.

Next, the solvent in the obtained organic layer was distilled off, and 59.4 g of crude 4'-methyl-2-cyanobiphenyl was distilled off.
(0.257 mol).

When the obtained crude 4′-methyl-2-cyanobiphenyl was subjected to HPLC analysis, the purity of 4′-methyl-2-cyanobiphenyl was 83.6% by weight, and the reaction yield was: 85.8 mol%.

Next, the obtained crude 4'-methyl-2-
When 59.4 g of cyanobiphenyl was purified by distillation, 46.0 g of 4′-methyl-2-cyanobiphenyl having a purity of 98.0% by weight was obtained.

Next, 4'-methyl-purified by distillation
46.0 g of 2-cyanobiphenyl was added to n-heptane 220
g of alumina, 2.2 g of alumina was added, and the mixture was heated at 50 to 60 ° C. for 30 minutes and stirred.

Thereafter, alumina was filtered off, crystals were precipitated by cooling, filtered, washed with n-heptane, and 40.0 g of 49.3 g of 4'-methyl-2-cyanobiphenyl having a purity of 99.3% by weight was obtained. Obtained. 4'-methyl-2 obtained
-The melting point of cyanobiphenyl was 52.9-53.5 <0> C.

Example 4 4.73 of manganese dioxide was placed in a 2 liter flask.
g (0.0544 mol), trimethylchlorosilane 2
3.64 g (0.2176 mol) and 956 g of tetrahydrofuran were charged and stirred at 40 to 45 ° C for 3 hours. Thereafter, o-chlorobenzonitrile
72 g (0.136 mol) were charged and cooled to -30 ° C.

Next, a tetrahydrofuran solution of p-methylphenylmagnesium chloride was placed in the flask.
28 g (concentration of p-methylphenylmagnesium chloride: 30.0% by weight, content of p-methylphenylmagnesium chloride: 0.85 mol), and 74.88 g (0.544 mol) of o-chlorobenzonitrile and tetrahydrofuran A mixed solution of 29.21 g with -35 to-
After dropping simultaneously at 30 ° C. over 6.5 hours, the reaction was carried out by keeping the temperature for 1 hour.

After completion of the reaction, 200 ml of 12% by weight hydrochloric acid was poured into the flask, and the mixture was allowed to stand for 30 minutes, followed by liquid separation. The separated organic layer was washed with 200 ml of 15% by weight saline solution.

Next, the solvent of the obtained organic layer was distilled off, and 132.6 g of crude 4'-methyl-2-cyanobiphenyl was distilled off.
(0.566 mol).

The obtained crude 4'-methyl-2-cyanobiphenyl was subjected to analysis using high performance liquid chromatography (HPLC analysis).
The purity of cyanobiphenyl was 82.5% by weight, and the reaction yield was 83.3 mol%.

From the above results, it can be seen that according to the methods of Examples 1 to 4, 2-cyanobiphenyl compounds can be easily obtained in high yield.

[0104]

According to the production method of the present invention, there is an excellent effect that a 2-cyanobiphenyl compound can be produced economically, simply and industrially.

──────────────────────────────────────────────────続 き Continuation of the front page (51) Int.Cl. ⁶ Identification code FI // C07B 61/00 300 C07B 61/00 300 (72) Inventor Nobutoshi Itaya 3-1-1, Utajima, Nishiyodogawa-ku, Osaka Fine Chem Co., Ltd.

Claims (2)

[Claims] After adding manganese dioxide and trimethylchlorosilane to an ether-based organic solvent, the compound of the general formula (I): (Wherein, R ¹ is an alkyl group having 1 to 6 carbon atoms,
A phenylmagnesium chloride compound represented by the following formula (I):
I): (Wherein R ¹ is the same as described above). 2. A compound of the general formula (I): (Wherein, R ¹ is an alkyl group having 1 to 6 carbon atoms,
Phenylmagnesium chloride compound represented by 6 an alkoxy group or a hydrogen atom) and after the reaction of ZnCl _2, the reaction product obtained in the o- chloro and benzonitrile Ni-based catalyst and the aprotic polar solvent Wherein the reaction is carried out in the presence of (Wherein R ¹ is the same as described above).