WO2004007433A1

WO2004007433A1 - Process for production of acylacetonitriles

Info

Publication number: WO2004007433A1
Application number: PCT/JP2003/008700
Authority: WO
Inventors: Hirofumi Nakagawa; Masatoshi Hayashi
Original assignee: Otsuka Chemical Co., Ltd.
Priority date: 2002-07-11
Filing date: 2003-07-09
Publication date: 2004-01-22
Also published as: JP2004043357A; TWI314548B; AU2003248250A1; TW200403213A

Abstract

A process for production of acylacetonitriles represented by the general formula (1) [wherein R1 is (C1-6 alkoxy)C1-4 alkyl or the like; X is halogeno, C1-6 alkyl, or C1-4 haloalkyl; Y is halogeno, C1-6 alkyl, or C1-4 haloalkyl; m is an integer of 1 to 3; and n is an integer of 1 to 3] by reacting an α-phenylcyanoacetate represented by the general formula (2) [wherein R1, X, and m are each as defined above] with a benzoyl halide represented by the general formula (3) [wherein Y and n are each as defined above] in the presence of a base and a phase transfer catalyst in a biphasic system consisting of an organic solvent and water. The process permits the production of acylacetonitriles of the general formula (1) in extremely high yield and is also excellent in environmental protection and safeness.

Description

Specification

Process for producing acylacetonitrile compound

Technical field

The present invention relates to a method for producing an acylacetonitrile compound.

Background technology

General formula (1)

[Wherein, R ¹ represents a C _2-4 alkenyl group, a C _2-4 alkynyl group, a (d-6 alkoxy) d-4 alkyl group, a '(d-4 alkylthio) d-4 alkyl group or a benzyl group. Shown. X and Y each represent a halogen atom, a d-6 alkyl group or a C, -48-octaalkyl group. m and n each represent an integer of 1 to 3. When m is 2 or 3, m Xs may be the same or different. When n is 2 or 3, n Ys may be the same or different. Is a compound useful as an acaricide, for example, as described in JP-A-2002-121181. Conventionally, an acylacetonitrile compound represented by the general formula (1) has been produced by, for example, a method shown in the following reaction formula-1.

Reaction formula 1

Wherein R ′, X, Y, m and n are the same as above. Z represents a halogen atom. As shown in Reaction Formula 11, the acylacetonitrile compound represented by the general formula (1) is represented by a phenylacetonitrile compound represented by the general formula (7) and a compound represented by the general formula (8a). The resulting carbonate compound is reacted in a solvent in the presence of a base to obtain a perfluorocyanoacetic acid ester compound represented by the general formula (4a) (step A). 4) It is produced by reacting an α-phenyl cyanoacetate compound represented by a) with a benzoyl halide compound represented by general formula (3) (step (2)).

However, the above method has a low yield of the desired acylacetonitrile compound represented by the general formula (1). This is apparent, for example, from Comparative Example 1 described below. (Ii) of Comparative Example 1 is a specific example corresponding to Step A of Reaction Formula 11 described above. In (Π) of Comparative Example 1, the yield of the reaction product is about 28% based on the starting compound. (Iii) of Comparative Example 1 is a specific example corresponding to the step B of the above reaction formula-1. In (iii) of Comparative Example 1, the yield of the reaction product is about 61% based on the starting compound. The total yield of the target compound (1) after these steps A and B is only about 17% based on the starting compound (7), which is industrially disadvantageous.

Moreover, the carbonate compound represented by the general formula (8a) used in the step A is a compound that is not commercially available and is difficult to obtain. The ester carbonate compound represented by the general formula (8a) usually needs to be separately synthesized using a phosgene compound as a raw material compound. However, since phosgene compounds are toxic, there are environmental and safety issues.

Therefore, the above methods are required to be further improved in terms of yield, environment, and safety.

Disclosure of the invention

An object of the present invention is to provide a method for industrially and advantageously producing an acylacetonitrile compound.

The present inventors have intensively studied to develop an industrially advantageous method for producing an acylacetonitrile compound. As a result, the object of the present invention can be achieved by performing the reaction between the α-phenylcyanoacetic acid ester compound and the benzoyl octalide compound in a two-phase system of an organic solvent and water in the presence of a base and a phase transfer catalyst. I found out. The present invention has been completed based on such knowledge.

The present invention provides the following method.

1. Two-phase organic solvent and water in the presence of a base and a phase transfer catalyst,

( ²⁾

[In the formula, R ^1, C ₂ - ₄ alkenyl group, C ₂ - 4 alkynyl group, alkoxy)

4 alkyl group, (Ci-4 alkylthio) Ct-4 alkyl group or benzyl group. X represents a halogen atom, a d- ₆ alkyl group or a d- ₄ haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, each of the m Xs may be the same or different. ]

A phenylcyanoacetic acid ester compound represented by the general formula (3)

[In the formula, Y represents a halogen atom, a d-6 alkyl group or a d-4 amino group. n shows the integer of 1-3. When n is 2 or 3, n Y's may be the same or different. Z represents a halogen atom. ]

By reacting with a benzoyl halide compound represented by the general formula (1) (1)

[Wherein, R ′, X, Y, m, and η are the same as described above. ]

For producing an acylacetonitrile compound represented by the formula:

2. General formula (4)

Wherein, R ² is C, - shows a ₆ alkyl group. X and m are the same as above. ]

The compound represented by the general formula (5)

R ^ H (5)

Wherein R ¹ is the same as above. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R X and m are the same as above. ]

Is obtained. Then, in the presence of a base and a phase-transfer catalyst, an organic solvent and water are used in a two-phase system to obtain α represented by the general formula (2) obtained above. —Phenylcyanoacetic acid ester compound and general formula (3)

(3)

Wherein Υ, η and 及び are the same as above. ]

With a benzoyl halide compound represented by the general formula (1)

[Wherein, R ¹ , X, Y, m, and n are the same as described above. ]

For producing an acylacetonitrile compound represented by the formula: 3. The reaction between the α-phenyl cyanoacetate compound of the general formula (4) and the alcohol compound of the general formula (5) is carried out by at least one catalyst selected from the group consisting of aluminum alkoxides and titanium alkoxides. General formula (6) formed by the reaction in the presence of

R ² OH (6)

Wherein R ² is the same as above. ]

3. The production method according to the above 2, wherein the alcohol represented by

4. General formula (7)

Wherein X and m are the same as above. ]

A phenylacetonitrile compound represented by the general formula (8)

(R ² 〇) ₂ CO (8)

Wherein R ² is the same as above. ]

Reacting with a carbonate compound represented by the general formula (4)

[Wherein, R ² , X and m are the same as above. ]

An α-phenyl cyanoacetate compound represented by the following general formula (4) is obtained.

R'OH (5)

[Wherein, R ′ is the same as described above. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R ′, X and m are the same as above. ]

To obtain an α-phenyl cyanoacetate compound represented by the following formula. Further, in the presence of a base and a phase transfer catalyst, a two-phase system of an organic solvent and water is used. Phenyl cyanoacetate compound and general formula (3)

[Wherein, Y, η and Ζ are the same as above. ]

With a benzoyl halide compound represented by the general formula (1)

[Wherein, R ¹ , X, Y, m, and n are the same as described above. ]

For producing an acylacetonitrile compound represented by the formula:

5. The reaction described in 4 above, wherein the reaction is performed while dropping an alcohol solution of an alkali metal alkoxide into the reaction system in reacting the phenylacetonitrile compound of the general formula (7) with the ester carbonate compound of the general formula (8). Manufacturing method

6. Alkali metal alkoxide has the general formula (9)

R ² 〇M (9)

Wherein R ² is the same as above. M represents an alkali metal atom. ]

An alkali metal alkoxide represented by the general formula (6)

R ² OH (6)

Wherein R ² is the same as above. ]

The production method according to the above 5, which is an alcohol represented by

7. The production method described in 5 or 6 above, in which the reaction is performed while removing the alcohol in the reaction system to the outside of the reaction system.

8. General formula (7)

Wherein X and m are the same as above. ]

A phenylacetonitrile compound represented by the general formula (8)

(R ² 〇) ₂ CO (8)

Wherein R ² is the same as above. ] Reacting with a carbonate compound represented by the general formula (4)

[Wherein, R ² , X and m are the same as above. ]

A method for producing a polyphenylacyanoacetate compound represented by the formula: wherein the reaction is carried out while an alcohol solution of an alkali metal alkoxide is dropped into the reaction system. Manufacturing method

9. General formula (4)

Wherein R ² is the same as above. X and m are the same as above. ]

Α-phenylcyanoacetic acid ester compound represented by the general formula (5)

R'OH (5)

Wherein R ¹ is the same as above. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R ′, X and m are the same as above. ]

A method for producing an α-phenyl cyanoacetate compound represented by the general formula (4), wherein the reaction between the —phenyl cyanoacetate compound of the general formula (4) and the alcohol compound of the general formula (5) is carried out by aluminum. General formula (6) formed by the reaction in the presence of at least one catalyst selected from the group consisting of alkoxides and titanium alkoxides

R ² 〇H (6)

Wherein R ² is the same as above. ]

A method for producing an α-phenylcyanoacetic acid ester compound while removing an alcohol represented by the formula

In the present specification, C ₂ - Examples ₄ alkenyl group, for example, vinyl group, 1-loop port pair group, Ariru group, isopropenyl group, 1 Buteniru group, 2-butenyl group, Examples thereof include linear or branched alkenyl groups having 2 to 4 carbon atoms, such as 3-butenyl group, 1-methyl-2-propenyl group, and 1,3-butenyl group.

The ₄ alkynyl group, for example, Echiniru group, 1 one-propynyl, 2-propynyl, 1 one methyl _ 2-propynyl group, 1 one Petit group, 2-heptynyl group, 3 - - C ₂ heptynyl group And a linear or branched alkynyl group having 2 to 4 carbon atoms.

Examples of the d- ₆ alkoxy group include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, Examples thereof include linear or branched alkoxy groups having 1 to 6 carbon atoms, such as isopentyloxy, neopentyloxy, n-hexyloxy, and isohexyloxy.

₄ Examples of the alkyl group include linear groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n_butyl group, isobutyl group, sec-butyl group and tert-butyl group. Or a branched alkyl group.

(0, -6 alkoxy) Ci-4 alkyl groups include, for example, methoxymethyl group, ethoxymethyl group, n-propoxymethyl group, isopropoxymethyl group, n-butoxymethyl group, sec-butoxymethyl group, tert —Butoxymethyl group, n —pentyloxymethyl group, n-hexyloxymethyl group, methoxyethyl group, ethoxyxetyl group, n-propoxyshethyl group, isopropoxyxyl group, n-butoxyxyl group, isobutoxyxyl group A straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms such as a butyl group, a sec-butoxyl group, a tert-butoxyl group, a 3-methoxypropyl group, a 3-ethoxypropyl group or a 3-ethoxybutyl group; Examples thereof include a linear or branched alkyl group having 1 to 4 carbon atoms and two substituents.

C, - As the _alkylthio group include a methylthio group, Echiruchio group, n- propylthio group, isopropylthio group, n _ Puchiruchio group, Isopuchiruchio group, sec - Puchiruchio group, tert - Puchiruchio carbon atoms such as groups 1-4 And a straight-chain or branched-chain alkylthio group. (C, -4alkylthio) d-4alkyl groups include, for example, methylthiomethyl group, methylthioethyl group, ethylthiomethyl group, ethylthioethyl group, ethylthiopropyl group, ethylthiobutyl group, n-propylthiomethyl group, isopropylthiomethyl group, A linear or branched alkyl group having 1 to 4 carbon atoms and having 1 or 2 alkylthio groups substituted with 1 to 4 carbon atoms such as an n-butylthioethyl group may be mentioned.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

₆ Examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, and a neopentyl group And straight-chain or branched-chain alkyl groups having 1 to 6 carbon atoms, such as n-hexyl group and isohexyl group.

Examples of the d- ₄ haloalkyl group include a fluoromethyl group, a chloromethyl group, a bromomethyl group, a chloromethyl group, a difluoromethyl group, a trifluoromethyl group, an 11-fluoroethyl group, a 2-fluoroethyl group, and a 2-chloroethyl group. , 2,2,2-Trifluoroethyl, Pentafluoroethyl, 1-Fluoropropyl, 2-Chloropropyl, 3_Fluoropropyl, 3-Chloropropyl, 1-Fluorobutyl, 1- Examples thereof include linear or branched alkyl groups having 1 to 9 carbon atoms, preferably 1 to 5 carbon atoms, such as chlorobutyl group and 4-fluorobutyl group, each of which is substituted with 1 to 9 halogen atoms.

In the present invention, R ¹ is preferably a (d- ₆ alkoxy) d- ₄ alkyl group.

The acylacetonitrile compound represented by the general formula (1) of the present invention is produced by the method shown in the following reaction formula-2. Reaction Formula 1 2

[Wherein, R X, Y, Z, m and η are the same as above. ]

The reaction between the α-phenyl cyanoacetate compound of the general formula (2) and the benzoyl halide compound of the general formula (3) is carried out by the reaction between an organic solvent and water in the presence of a base and a phase transfer catalyst. Performed in a two-phase system.

As the organic solvent, an organic solvent having substantially no adverse effect on the above reaction, having low affinity and solubility with water, and forming a two-phase system with water is used. Such organic solvents include, for example, aliphatic or alicyclic hydrocarbons such as η-hexane, cyclohexane, η-heptane and η-octane; and aromatic hydrocarbons such as toluene, xylene, and cyclobenzene. Hydrogen; halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, chloroform and carbon tetrachloride; and esters such as methyl acetate and ethyl acetate.

Among these organic solvents, aromatic hydrocarbons are preferred, and toluene, black benzene and the like are more preferred.

One of the above organic solvents can be used alone, or two or more can be used as a mixture.

The amount of the organic solvent used is usually about 0.5 to 20 parts by weight, preferably about 2 to 4 parts by weight, per 1 part by weight of the α-phenylcyanoacetate ester compound represented by the general formula (2). However, it is not limited to these.

Examples of the water used in combination with the organic solvent include, but are not limited to, pure water, distilled water, deionized water, and tap water.

The amount of water used is about 1 to 15 parts by weight, preferably about 1.5 to 4 parts by weight, per 1 part by weight of the monophenyl cyanoacetate compound represented by the general formula (2). However, the present invention is not limited to these. It is more preferable to use about 1 to 1.5 parts by weight of water with respect to 1 part by weight of the organic solvent.

As the base in the above reaction, known bases can be widely used, and examples thereof include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates such as potassium carbonate, sodium carbonate and sodium hydrogen carbonate. No. Among these, alkali metal carbonates such as potassium carbonate, sodium carbonate and sodium hydrogen carbonate are preferred.

These bases can be used alone or in combination of two or more. The amount of the base to be used is generally about 0.5 to 5 mol, preferably 1 to 1.5 mol, per 1 mol of the α-phenyl cyanoacetate ester compound represented by the general formula (2). It is about.

In the present invention, the base is preferably used by dissolving in water used as the above-mentioned reaction solvent.

As the phase transfer catalyst in the above reaction, known phase transfer catalysts can be widely used, and examples thereof include quaternary ammonium salts, quaternary phosphonium salts, and ether-based catalysts.

The quaternary ammonium salts, for example, tetra (d - ₄ alkyl) Anmoniumu halide, benzyltri (C, - ₄ alkyl) halides, and the like. Tetra - Specific examples of (d ₄ alkyl) ammonium Niu beam halides, tetra-n- butyl ammonium Niu skeleton chloride, Ru tetra n- Petit Ruan monitor © beam bromide and the like. Benzyltri (C, - ₄ alkyl) Specific examples of the halides, benzyltri-methyl ammonium Niu skeleton chloride, benzyltrimethylammonium E chill ammonium Niu skeleton chloride and the like can be mentioned up.

The quaternary Hosuhoniumu salts, for example, Te us (C, - ₄ alkyl) Hosuhoniu Muharaido the like. Tetra (C, - ₄ alkyl) Specific examples of the phosphonyl © beam halides, tetra E chill phosphonyl © beam bromide, Te we n- Buchiruhosuho Niumuburomido the like.

More specifically, examples of the ether catalyst include dibenzo-18-crown-6. Among these phase transfer catalysts, quaternary ammonium salts are preferable, and tetra-n-butylammonium chloride, tetra-n-butylammonium bromide and the like are more preferable.

One of these phase transfer catalysts can be used alone, or two or more can be used in combination.

The amount of the phase transfer catalyst to be used is generally about 0.01 to 0.2 mol, preferably about 0.0 mol, per 1 mol of the α-phenyl cyanoacetate ester compound represented by the general formula (2). It is about 0.3 to 0.05 mol.

In the reaction of the present invention, for example, the α-phenyl cyanoacetate ester compound represented by the general formula (2) is dissolved in the organic solvent, the base is dissolved in water, and then these solutions are mixed. The above-mentioned phase transfer catalyst is added to the obtained two-phase solvent, and the benzoyl halide compound represented by the general formula (3) is added dropwise, whereby the process proceeds suitably. The amount of the benzoyl halide compound represented by the general formula (3) is generally about 5 to 2 mol, preferably 1 to 2 mol per mol of the monophenyl cyanoacetate compound represented by the general formula (2). Is about 0.9 to 1.2 mol.

The reaction temperature of the above reaction is usually in the range of 0 to the boiling point of the organic solvent to be used or lower, preferably in the range of 20 to 30, but is not limited thereto.

This reaction is carried out usually for about 1 to 10 hours, preferably for about 3 to 6 hours, depending on the reaction temperature and the like.

The target compound obtained by the above reaction can be easily isolated from the reaction mixture by commonly used isolation means such as filtration, solvent extraction, distillation, recrystallization and the like. It is purified by known purification means. In the above reaction, the benzoyl halide compound of the general formula (3) used is a known compound or a compound which can be easily produced according to a known method. Further, the α-phenyl cyanoacetate compound of the general formula (2) is produced according to the method shown in the following reaction formula 13. Reaction formula 1 3

(2)

Wherein RR ² , X and m are the same as above. ]

As shown in Reaction Scheme 13, the α-phenylcyanoacetate ester compound represented by the general formula (4) is represented by the phenylacetonitrile compound represented by the general formula (7) and the compound represented by the general formula (8). It is produced by reacting with a carbonate compound to be prepared. Next, the α-phenyl cyanoacetate compound represented by the general formula (2) is composed of an α-phenyl cyanoacetate compound represented by the general formula (4) and an alcohol compound represented by the general formula (5). And is produced by reacting

First, the reaction between the phenylacetonitrile compound of the general formula (7) and the carbonate compound of the general formula (8) will be described.

The phenylacetonitrile compound represented by the general formula (7) and the ester carbonate compound represented by the general formula (8) are easily available known compounds or are easily produced according to known methods.

As the carbonate compound represented by the general formula (8), various compounds in which R ² represents a Ci-6 alkyl group can be used. Preferred carbonic ester compound, C, - ₂ compound is Al kill group, i.e., a dimethyl carbonate and carbonate Jechiru. Dimethyl carbonate is more preferred.

The amount of the carbonate compound represented by the general formula (8) is usually about 1 to 20 mol, preferably about 3 to 6 mol, per 1 mol of the phenylacetonitrile compound represented by the general formula (7). It is.

Phenylacetonitrile compound of the general formula (7) and carbonate ester of the general formula (8) In reacting the compound with the compound, it is preferable that an alkali metal alkoxide is present in the reaction system.

Examples of the alkali metal alkoxide include d-4 saturated aliphatic alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, and tert-butyl alcohol, and alkali metals. And the like. Among them, alkali metal alkoxides obtained from methanol or ethanol and alkali metals are preferable, and sodium methoxide and sodium ethoxide are particularly preferable.

In order to prevent a side reaction of this reaction, an alkali metal alkoxide obtained from an alcohol composed of the same alkyl as the ester portion (R ² ) of the carbonate compound represented by the general formula (8) and an alkali metal; ^It is preferable to use an alkali metal alkoxide represented by ² OM (wherein, R ² is the same as above, and M represents an alkali metal atom).

The amount of the alkali metal alkoxide to be used is generally about 1 to 5 mol, preferably about 1.2 to 2 mol, per 1 mol of the phenylacetonitrile compound represented by the general formula (7).

According to the study of the present inventors, when a phenylacetonitrile compound represented by the general formula (7) is dropped into a toluene solution of an alcohol solution of an alkali metal alkoxide and a carbonate compound represented by the general formula (8), It was found that, since the reaction was exothermic, foaming occurred in the reaction system as the reaction proceeded, and it was not possible to cope with scale-up. Therefore, in the present invention, an alkali metal alkoxide is dissolved in alcohol to form an alcohol solution, and the solution is added to a reaction solution containing a phenylacetonitrile compound of the general formula (7) and a carbonate compound of the general formula (8). It is particularly preferable that the reaction is allowed to proceed by dropwise addition, because foaming can be suppressed and operational safety can be ensured.

In this reaction, by adding an alcohol solution of the alkali metal alkoxide dropwise to the reaction solution, side reactions can be suppressed, and the yield can be improved. The alcohol used as the alcohol solution of the alkali metal alkoxide is usually an alcohol composed of the same alkyl group as the alkali metal alkoxide portion used (that is, R ² OH, wherein R ² is The same is true for).

The concentration of the alkali metal alkoxide in the alcohol solution is usually about 5 to 35% by weight, preferably about 25 to 30% by weight.

The lowering speed of the alcohol solution of the alkali metal alkoxide can be appropriately selected depending on the concentration of the solution, the reaction scale, the temperature, the progress of the reaction, and the like.

Examples of the solvent used in this reaction include hydrocarbons such as toluene, xylene, benzene, heptane, and octane; ethers such as tetrahydrofuran, dioxane, and diisopropyl ether.

The amount of these solvents to be used is generally about 1 to 10 parts by weight, preferably about 2 to 5 parts by weight, per 1 part by weight of the phenylacetonitrile compound represented by the general formula (7). It is not limited to these.

In this reaction, an alcohol (ie, an alcohol represented by the general formula R ² OH) generated as the reaction proceeds in the reaction system, and an alcohol in an alcohol solution of the alkyl metal alkoxide (ie, the general formula R ² (Alcohol represented by OH) is preferably removed from the reaction system. In this case, a solvent having a boiling point higher than the boiling point of the alcohol is preferably used.

In the present invention, it is desirable to carry out the reaction while dropping the same amount of an alkali metal alkoxide-alcohol solution in the reaction system as the amount of alcohol removed outside the reaction system.

This reaction may be performed under reduced pressure in consideration of the boiling point of the alcohol to be removed out of the system, the boiling point of the solvent used, the reaction temperature, and the like. When the reaction is carried out under reduced pressure, the pressure in the reaction system is usually about 6666 Pa to 6666 Pa, preferably about 33330 Pa to 53333 Pa. Is good.

The reaction temperature of this reaction can be appropriately set in the range of usually 50 to around the boiling point of the solvent, preferably about 70 to 100 ° C., in consideration of the boiling point and the degree of reduced pressure of the solvent used. . This reaction is carried out usually for about 1 to 10 hours, preferably for about 2 to 5 hours, depending on the reaction temperature.

Next, the reaction between the phenylacetonitrile compound of the general formula (4) and the alcohol of the general formula (5) will be described.

This reaction is preferably carried out in the presence of at least one catalyst selected from the group consisting of aluminum alkoxides and titanium alkoxides, while removing the alcohol formed as the reaction proceeds outside the reaction system.

This reaction can be carried out in an appropriate solvent. However, the alcohol compound represented by the general formula (5) used as a reaction reagent is used in a large excess, and the alcohol compound is also used as a reaction solvent. Is preferred.

Examples of the solvent used include aliphatic or alicyclic hydrocarbons such as n-hexane, cyclohexane, n-heptane and n-octane; and aromatic hydrocarbons such as toluene, xylene, and benzene. Halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, chloroform and carbon tetrachloride; and esters such as methyl acetate and ethyl acetate.

Examples of the alcohol compound (ΙΤ ΟΗ) represented by the general formula (5) used in this reaction include, for example, 1-propenyl alcohol, aryl alcohol, isopropenyl alcohol, 1-butenyl alcohol, 2-butenyl alcohol. Thenyl alcohol, 3-butenyl alcohol, 1-methyl-2-propenyl alcohol, 1,3-butenyl genyl alcohol, ethynyl alcohol, 1-propynyl alcohol, 2-propynyl alcohol, 1-methyl — 2-propynyl alcohol, 1-butynyl alcohol, 2-butynyl alcohol, 3-butynyl alcohol, methoxymethyl alcohol, ethoxymethyl alcohol, n-propoxymethyl alcohol, isopropoxymethyl alcohol, n-butoxymethyl Alcohol, sec—butoxymethyl alcohol, tert—but Cimethyl alcohol, n-pentyloxymethyl alcohol, n-hexyloxymethyl alcohol, methoxyethyl alcohol, ethoxyethyl alcohol, n-propoxyethyl alcohol, isopropoxyethyl alcohol, n-butoxyethyl alcohol, isobutoxy Tyl alcohol, sec-butoxyethyl alcohol, tert-butoxyshetila Alcohol, 3-methoxypropyl alcohol, 3-ethoxypropyl alcohol, 3-ethoxybutyl alcohol, methylthiomethyl alcohol, methylthioethyl alcohol, ethylthiomethyl alcohol, ethylthioethyl alcohol, ethylthiopropyl alcohol, ethylthiobutyl alcohol , N-propylthiomethyl alcohol, isopropylthiomethyl alcohol, n-butylthioethyl alcohol, cyclohexyl alcohol, benzyl alcohol and the like. The amount of the alcohol compound represented by the general formula (5) is usually about 1 to 10 mol, preferably 2 to 1 mol per 1 mol of the α-phenylcyanoacetate compound represented by the general formula (4). The amount may be about 4 to about 4 mol, but when it is also used as a reaction solvent, it is usually about 2 to 20 mol and preferably about 7 to 15 mol.

The catalyst used in this reaction is at least one selected from the group consisting of aluminum alkoxides and titanium alkoxides.

As the aluminum alkoxide, for example, the general formula (10)

A 1 (OR ⁴ ) 3 (10)

[Wherein, R ⁴ represents a _4- alkyl group. ]

And known aluminum alkoxides, such as aluminum alkoxide, and more specifically, aluminum ethoxide, aluminum isopropoxide, aluminum trisec-butoxide and the like.

As the titanium alkoxide, for example, the general formula (11)

T i (OR ⁴ ) 4 (1 1)

Wherein R ⁴ is the same as above. ]

Known titanium alkoxides such as titanium alkoxides represented by the following formulas, and more specifically, tetraisopropyl titanate, tetra n-butyl titanate and the like.

One of these catalysts can be used alone, or two or more of them can be used in combination.

The amount of the catalyst used is usually about 0.01 to 1 mol, preferably 0.1 to 0.2 mol, per 1 mol of the α-phenylcyanoacetate ester compound represented by the general formula (4). It is about. When performing the reaction while removing the alcohol generated in the reaction process outside the reaction system, the pressure should be reduced in consideration of the boiling point of the excluded alcohol, the boiling point of the alcohol compound represented by the general formula (5), and the reaction temperature. The reaction may be performed below. For example, the general formula

When the boiling point of the alcohol compound represented by (5) is 100 or more, the reaction is preferably performed under reduced pressure.

When the reaction is carried out under reduced pressure, the degree of reduced pressure is usually about 6666 Pa to 6666 OPa, preferably about 33330 Pa to 53328 Pa.

The reaction temperature of this reaction is usually from 50 ° C. in consideration of the boiling point and the degree of vacuum of the alcohol compound represented by the general formula (5) to be used, or the alcohol compound represented by the general formula (5). Below, preferably within the range of about 80 to 130 ° C.

This reaction is carried out usually for about 1 to 15 hours, preferably for about 4 to 8 hours, depending on the reaction temperature.

Each product obtained in each of the above reactions is easily isolated from the reaction mixture by commonly used isolation means such as, for example, filtration, solvent extraction, distillation, and recrystallization, and further, for example, column chromatography. It is purified by commonly used purification means such as chromatography.

In the method of the present invention, the α-phenyl cyanoacetate compound of general formula (4) and the α-phenyl cyanoacetate compound of general formula (2) obtained as shown in Reaction Scheme 13 are It can be used for the subsequent reaction without isolating and purifying it from the reaction mixture or by performing a simple purification operation, for example, a solvent extraction operation.

The invention's effect

According to the method of the present invention, the acylacetonitrile compound represented by the general formula (1) can be industrially advantageously produced.

In each of the reaction processes for producing the acylacetonitrile compound represented by the general formula (1), each reaction product is obtained in high yield. Therefore, the target compound ( 1) can be produced in extremely high yield.

Also, there are no raw materials for producing the acylacetonitrile compound represented by the general formula (1). The method of the present invention is also excellent in environmental and safety aspects because the compound is easily available and has low toxicity.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.

The ¹ H-NMR data described in the following Examples were obtained using a 300 MHz NMR measuring instrument and tetramethylsilane (TMS) as a reference substance. The purity of the target compound was determined by the absolute calibration curve method of high performance liquid chromatography (HPLC).

Example 1

(1-a) Production of methyl 2- (4-tert-butylphenyl) cyanoacetate (4)

A thermometer, a dropping funnel and a distillation column were attached to a 500 ml three-necked flask, and a condenser and a receiver were attached to the distillation column.

In this flask, 43.3 g (0.25 mol) of 4-tert-butylphenylacetonitrile, 115 ml of dimethyl carbonate (1.25 mol) and 170 ml of toluene were placed, and this mixed solution was stirred at 75 to 8 Ot. : Heated. 62 g (0.325 mol) of a 28% (w / v) methanol solution of sodium methoxide was added dropwise from the dropping funnel to the mixed solution over 30 minutes. The temperature of the mixed solution was maintained at 75 to 80 ° C, and an azeotropic mixture of methanol, toluene and dimethyl carbonate vaporized from the start of the dropwise addition was collected in a receiver of a distillation apparatus, and methanol was removed to the outside of the reaction system.

100 minutes after the completion of the dropwise addition, the reaction solution was cooled to about 50 ° C. 2- (4-tert-butylphenyl) Dilute the reaction solution in which the sodium salt of methyl cyanoacetate has precipitated, returning a part of the azeotrope in the receiver to such an extent that stirring is easy, and cooling to 20 did. To this solution, 110 ml of 12% (w / v) hydrochloric acid was added dropwise to neutralize the solution. This solution was allowed to stand for 10 minutes, the aqueous phase was separated and removed, and the obtained organic phase was washed with 30 ml of water, and then concentrated under reduced pressure to obtain a yellow-brown oily 2- (4-tert-butylphenyl) cyano. Methyl acetate was obtained.

Yield: 57.8 g, Purity: 98%, Yield: 98.0%

_{Ή-NMR (CDC 1 3,} δ pm): 1.32 (s, 9H), 3.81 (s, 3H), 4.71 (s, 1H), 7.41 (dd, 4H)

(1-b) 2- (4-tert-butylphenyl) 2-methoxyethyl cyanoacetate (2)

A thermometer and a distillation column were attached to a 500 ml three-necked flask, and a cooler, a receiver, and a pressure reducer were attached to the distillation column.

In this flask, 56.7 g (purity: 98%, 0.24 mol) of methyl 2- (4-tert-butylphenyl) cyanoacetate prepared in the above (1-a), 200 ml of 2-methoxyethanol (2 .5 mol) and 5.1 g (0.025 mol) of aluminum isopropoxide, and the mixture was stirred for 5 hours at an internal pressure of 39996 to 46662 Pa and an oil bath temperature of 100 to 110. During this time, the vaporized alcohol was constantly collected in the receiver of the distillation apparatus and removed outside the reaction system.

After completion of the reaction, unreacted 2-methoxyethanol was completely distilled off under reduced pressure, and 125 ml of toluene was added to the obtained residue. To the obtained toluene solution, 85 ml of 9% (wZv) sulfuric acid was added with 2 O: and the mixture was vigorously stirred for 30 minutes. This solution was allowed to stand for 15 minutes, and the aqueous phase was separated and removed to obtain a toluene solution of 2-methoxyethyl 2- (4-tert-butylphenyl) cyanoacetate.

A very small portion of the toluene solution was withdrawn and concentrated, and the residue obtained was analyzed by NMR. The residue was confirmed to be the desired 2-methoxyethyl 2- (4-tert-butylphenyl) cyanoacetate. did.

Ή-NMR (CDC 13, δ p m):

1.32 (s, 9H), 3.09 (s, 3H),

3.6-3. 65 (m, 2H), 4.3-4. 35 (m, 2H),

4.75 (s, 1 H), 7.40 (d, 2 H), 7.41 (d, 2H) (1-c) 2— (4-tert-butylphenyl) — 2— (2— Preparation of trifluoromethylbenzoyl) cyanoacetic acid 2-methoxyethyl (1)

A thermometer and a dropping funnel were attached to a 1000 ml three-necked flask. Into this flask was added the entire toluene solution of 2-methoxyethyl 2- (4-tert-butylphenyl) cyanoacetate prepared in (1-b) above, and potassium carbonate 38 g (0.275 mol) and 0.8 g (0.0025 mol) of tetra-n-butylammonium bromide in 120 ml of water were added to obtain a two-phase reaction solution.

While stirring the reaction solution at 20 to 30, 52 g (0.25 mol) of 2-trifluoromethylbenzoyl chloride was added dropwise thereto. After completion of the dropwise addition, the mixture was stirred for 2.5 hours while maintaining the reaction solution at 20 to 3 Ot :, and then the aqueous phase was separated and removed. The obtained organic phase was washed with 3 Oml of water, and then concentrated under reduced pressure.

175 ml of isopropyl alcohol was added to the obtained residue, and the obtained mixture was stirred at 0 to precipitate crystals. The crystals were collected by filtration, washed with 50 ml of isopropyl alcohol (5) and dried under reduced pressure to give 2- (4-tert-butylphenyl) 1-2- (2-trifluoromethylbenzoyl) as yellowish-white crystals. ) Cyanoacetic acid 2-methoxyl was obtained.

Yield: 98.6 g

Yield: 90.4% (Yield based on methyl 2- (4-tert-butylphenyl) cyanoacetate)

Purity: 98.6%

_{Ή-NMR (CDC 1 3,} (5 p pm):

1.35 (s, 9H), 3.36 (s, 3H),

3.6-3.65 (m, 2H), 4.4—4.5 (m, 2H),

7.14 (d, 1H), 7.4—7.6 (m, 6H), 7.78 (d, 1H) The starting compound of Example 1 (1-a), —2_ (4-tert-Butylphenyl) 1-2- (2-trifluoromethylbenzoyl) based on butylphenylacetate nitrile Total yield of 2-methoxyethyl ethyl cyanoacetate is 86.9 %Met.

Example 2

(2-a) Preparation of 2- (4-chlorophenyl) methyl cyanoacetate (4)

A thermometer, a dropping funnel, and a distillation column were attached to a three-necked flask of 50 Om1, and a condenser and a receiver were attached to the distillation column.

37.8 g (0.25M) of 4-necked phenylacetonitrile G), dimethyl carbonate (115 ml) (1.25 mol) and toluene (170 ml) were added, and the resulting mixed solution was heated to 75 to 80 with stirring. 62 g (0.325 mol) of a 28% (w / v) methanol solution of sodium methoxide was added dropwise from the dropping funnel to the mixed solution over 35 minutes. The temperature of the mixed solution was maintained at 75 to 80 ° C, and an azeotropic mixture of toluene / methanol / dimethyl carbonate vaporized from the start of the dropwise addition was collected in a receiver of a distillation apparatus, and methanol was removed to the outside of the reaction system.

After 90 minutes from the end of the dropwise addition, the reaction solution was cooled to about 50 50. 2- (4-chlorophenyl) To the reaction solution in which the sodium salt of methyl cyanoacetate was precipitated, a part of the azeotrope in the receiver was returned, diluted to such an extent that stirring was easy, and further cooled to 18 . To this reaction solution, 110 ml of 12% (w / v) hydrochloric acid was added dropwise to neutralize the reaction solution. The reaction solution was allowed to stand for 10 minutes, the aqueous phase was separated and removed, and the obtained organic phase was washed with 3 Oml of water, and then concentrated under reduced pressure to obtain a brown oily 2- (4-chlorophenyl) phenylamine. Methyl monoacetate was obtained.

Yield: 52.4 g, Purity: 98%, Yield: 98.2%

_{Ή-NMR (CDC 1 3>} 6 p pm):

3.81 (s, 3H), 4.72 (s, 1H), 7.41 (s, 4H)

(2-b) 2- (4-chlorophenyl) 2-methoxyethyl cyanoacetate (2) A thermometer and a distillation column were attached to a 500 ml three-necked flask, and a cooler, receiver and A vacuum was attached.

In this flask, 51.6 g (purity 98%, 0.24 mol) of methyl 2- (4-chlorophenyl) cyanoacetate prepared in the above (2-a), 200 ml of 2-methoxyethanol (2.5 Mol) and aluminum isopropoxide 5.1 g

(0.025 mol), and the mixture was stirred for 5 hours at an internal pressure of 39996 to 46662 Pa and an oil bath temperature of 100 to 110. During this time, the vaporized alcohol was constantly collected in the receiver of the distillation apparatus and removed outside the reaction system.

After completion of the reaction, unreacted 2-methoxyethanol was completely distilled off under reduced pressure, and 125 ml of toluene was added to the obtained residue. To the obtained toluene solution, 85 ml of 9: 9 (w / v) sulfuric acid was added at 20:20, and the mixture was vigorously stirred for 30 minutes. The solution was allowed to stand for 15 minutes, the aqueous phase was separated and removed, and the toluene was concentrated under reduced pressure to give a brown oil. (4-Methyl phenyl) 2-methoxyethyl cyanoacetate was obtained. Yield: 59.9 g, purity: 96%, yield: 94.0%

_{Ή-NMR (CDC 1 3,} (5 p pm):

3.34 (s, 3H), 3.57-1 360 (m, 3H),

4. 32—4.36 (m, 2H), 476 (s, 1H),

7. 41 (s, 4H)

Preparation of (2-c) 2- (4-chlorophenol) -2 (2-trifluoromethylbenzoyl) 2-methoxyethyl cyanoacetate (1)

A thermometer and a dropping funnel were attached to a 1 000 m 1 three-necked flask, and the 2- (4-chlorophenyl) cyanoacetic acid 2-methoxyshethyl prepared in (2-b) above was placed in a flask. 59. O g (Purity 96%, 0.223 mol) and toluene 125 ml were added, and potassium carbonate 38 g (0.275 mol) and tetra-n-butylammonium bromide 0.8 g (0.20025 mol) were added to water 12 Om 1. An aqueous solution dissolved in was added to obtain a two-phase reaction solution.

50 g (0.24 mol) of 2-trifluoromethylbenzoyl chloride was added dropwise while stirring the reaction mixture at 20 to 3 O :. After completion of the dropwise addition, the mixture was stirred for 3 hours while maintaining the reaction solution at 20 to 30, and then the aqueous phase was separated and removed. The organic phase obtained is washed with water

After washing with 30 ml, it was concentrated under reduced pressure.

12 Oml of isopropyl alcohol was added to the obtained residue, and the mixture was stirred at 0 to precipitate crystals. The crystals are collected by filtration, washed with 5 Om 1 of isopropyl alcohol at 5 ° C, dried under reduced pressure, and yellow-white crystals of 2- (4-chlorophenyl) -2- (2-trifluoromethylbenzoyl) 2) 2-Methoxyethyl cyanoacetate was obtained.

Yield: 90 g, Purity: 98.5%, Yield: 93.3%

_{Ή-NMR (CDC 1 3,} δ p pm):

3.36 (s, 3Η), 3.62-3.65 (m, 2Η),

4.5—4.6 (m, 2H), 7.2 (d, 1H),

7.48-7.7 (m, 6 H), 7.82 (d, 1 H)

In addition, 2- (4-chlorophenyl) 1-2- (2-tri) from 4-chlorophenylacetonitrile which is the starting compound of Example 2 (2-a) The total yield for the production of 2-methoxyethyl cyanoacetate was 83.5%. Comparative Example 1

(1) Production of dimethoxyethyl carbonate (8)

A solution of 4.6 g (0.06 mol) of 2-methoxyethanol and 6.1 g (0.06 mol) of triethylamine in 50 ml of tetrahydrofuran (THF) was stirred under ice-cooling, and 2.9 g (0.01 mol) of triphosgene was added thereto. Mol) in THFlOml was added dropwise. After completion of the dropwise addition, the reaction solution was stirred at 20 for 30 minutes, and then 30 ml of water was added to the reaction solution, followed by extraction with 100 ml of ethyl acetate. The extract was dried over anhydrous magnesium sulfate, insolubles were removed by filtration, and the filtrate was concentrated to obtain 5.4 g of crude dimethoxyethyl carbonate.

(ii) 2- (4-tert-butylphenyl) cyanoacetate 2-methoxyethyl

(2) Manufacture

A suspension of 3.9 g (0.0225 mol) of 4_ tert-butylphenylacetonitrile and 1.8 g (0.045 mol) of sodium hydride (60% oil) in 50 ml of THF was heated to reflux and added to the above solution. A solution of 8.1 g of crude dimethoxyethyl carbonate prepared in (i) in 10 ml of THF was added dropwise. After completion of the dropwise addition, the reaction solution was heated to reflux for 1 hour, and then cooled to 10. Water 3 Om1 was added to the reaction solution, and extracted with 100 ml of ethyl acetate. The extract was dried over anhydrous magnesium sulfate, insolubles were removed by filtration, and the filtrate was concentrated. The obtained residue was purified by a silica gel column (n-hexane Z-ethyl acetate = 6Z1, volume ratio) to obtain 2- (4-tert-butylphenyl) cyanoacetate 2-methoxethyl.

Yield: 1.8 g, Purity: 96%, Yield: 27.9%

(Ex) 2- (4-tert-butylphenyl) -2- (trifluoromethylbenzoyl) Preparation of 2-methoxyethyl cyanoacetate (1)

A solution of 1.8 g (purity 96%, 0.0063 mol) of 2- (4-tert-butylphenyl) cyanoacetate prepared in (ii) above in 30 ml of THF was stirred under ice-cooling with sodium hydride. (60% oil) 0.3 g (0.0075 mol) was added, and the mixture was stirred for 10 minutes. To this solution was added dropwise a solution of 1.4 g (0.007 mol) of 2-trifluoromethylbenzoyl chloride in THF 1 Om1. Dripping After completion, the reaction solution was stirred at 20 for 1 hour, and then 50 ml of water was added to the reaction solution, followed by extraction with 10 mL of ethyl acetate. After the extract was dried over anhydrous magnesium sulfate, insolubles were removed by filtration, and the filtrate was concentrated. The resulting residue was subjected to silica gel column chromatography (n-hexane / "ethyl acetate = 31, volume ratio). Then, 2- (4-tert-butylphenyl) -2- (trifluoromethylbenzoyl) cyanoacetate 2-methoxyethyl was obtained.

Yield: 1.8 g, Purity: 95%, Yield: 60.9%

Claims

The scope of the claims

1. In the presence of a base and a phase transfer catalyst, a two-phase system of an organic solvent and water, represented by the general formula (2)

[Wherein, R ¹ represents a C _2-4 alkenyl group, a C _2-4 alkynyl group, a (C, -6 alkoxy) alkyl group, a (C, -4 alkylthio) C, -4 alkyl group or a benzyl group. You. X represents a halogen atom, d-6 alkyl group or d-4 haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, each of the m Xs may be the same or different. ]

Α-phenylcyanoacetic acid ester compound represented by the general formula (3)

[Wherein, Υ represents a halogen atom, a 6 alkyl group or a d-4 peralkyl group. n shows the integer of 1-3. When n is 2 or 3, n Y's may be the same or different. Z represents a halogen atom. ]

By reacting with a benzoyl halide compound represented by the general formula (1)

[Wherein, R ′, X, Y, m, and n are the same as described above. ]

A method for producing an acylacetonitrile compound represented by the formula:

2. General formula (4)

[Wherein, R ² represents a _6- alkyl group. X is a halogen atom, is also ₆ alkyl C, - shows a ₄ haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, m Xs may be the same or different. ] The α-phenyl cyanoacetate compound represented by the general formula (5)

R'OH (5)

[In the formula, R ^1, C ₂ - ₄ alkenyl group, C ₂ - ₄ alkynyl group, (CI- ₆ alkoxy)

C, - ₄ alkyl group, an alkylthio) d - shows the 4 alkyl group or a benzyl group. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R X and m are the same as above. J

A step of obtaining a monophenyl cyanoacetate compound represented by the formula: and a two-phase system of an organic solvent and water in the presence of a base and a phase transfer catalyst, represented by the general formula (2) obtained above Hyphenylcyanoacetic acid ester compound and general formula (3)

[In the formula, Y is a halogen atom, C, - shows a ₆ alkyl group or a haloalkyl group. n shows the integer of 1-3. When n is 2 or 3, n Y's may be the same or different. Z represents a halogen atom. ]

Reacting with a benzoyl halide compound represented by the formula:

General formula (1) including

[Wherein, R ′, X, Y, m, and n are the same as described above. ]

A method for producing an acylacetonitrile compound represented by the formula:

3. The reaction between the α-phenyl cyanoacetate compound of the general formula (4) and the alcohol compound of the general formula (5) is carried out by at least one catalyst selected from the group consisting of aluminum alkoxides and titanium alkoxides. In the presence of and by the reaction Generating general formula (6)

R ² 0H (6)

[Wherein, R ² is the same as defined in claim 2]. ]

3. The production method according to claim 2, wherein the reaction is performed while removing the alcohol represented by the formula (1) outside the reaction system.

4. General formula (7)

[In the formula, X represents a halogen atom, a C ₆ -6 alkyl group or a d-4 haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, each of the m Xs may be the same or different. ]

A phenylacetonitrile compound represented by the general formula (8)

(R ² 〇) ₂ CO (8)

[Wherein, R ² represents a d-6 alkyl group. X represents a halogen atom, a d-6 alkyl group or a d-4 haloalkyl group. ]

Reacting with a carbonate compound represented by the general formula (4)

[Wherein, R ² , X and m are the same as above. ]

Obtaining an α-phenyl cyanoacetate compound represented by the formula:

The resulting phenyl cyanoacetate compound represented by the general formula (4) is added to the general formula (5)

R'OH (5)

[In the formula, R ¹ represents a C _2-4 alkenyl group, a C _2-4 alkynyl group, a (d-6 alkoxy) alkyl group, a (d-4 alkylthio) C -4 alkyl group or a benzyl group. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R ′ X and m are the same as above. ]

A step of obtaining a perfluorocyanoacetate compound represented by the formula: and a two-phase system of an organic solvent and water in the presence of a base and a phase transfer catalyst, represented by the general formula (2) obtained above Hyphenylcyanoacetic acid ester compound and general formula (3)

[In the formula, Y represents a halogen atom, a d-6 alkyl group or a CH haloalkyl group. n represents an integer of 13. When n is 2 or 3, n Y's may be the same or different. Z represents a halogen atom. ]

Reacting with a benzoyl octalide compound represented by the formula:

General formula (1) including

[Wherein, R ′ X Y m and η are the same as above. ]

A method for producing an acylacetonitrile compound represented by the formula:

5. In reacting the phenylacetonitrile compound of the general formula (7) with the ester carbonate compound of the general formula (8), the reaction is carried out while dropping an alcohol solution of an alkali metal alkoxide into the reaction system. The production method according to item 4.

6. Alkali metal alkoxide has the general formula (9)

R ² OM (9)

[Wherein, R ² is the same as in claim 4]. M represents an alkali metal atom. Is an alkali metal alkoxide represented by the general formula (6)

R ² OH (6)

Wherein R ² is the same as above. ] 6. The production method according to claim 5, which is an alcohol represented by the formula:

7. The production method according to claim 5, wherein the reaction is performed while removing the alcohol in the reaction system to the outside of the reaction system.

8. General formula (7)

[Wherein, X is a halogen atom, _d-6 alkyl or - indicates a ₄ haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, each of the m Xs may be the same or different. ]

A phenylacetonitrile compound represented by the general formula (8)

(R ² 〇) ₂ CO (8)

[In the formula,! ^ Represents an alkyl group. ]

Reacting with a carbonate compound represented by the general formula (4)

[Wherein, R ² , X and m are the same as above. ]

A method for producing a phenyl cyanoacetate compound represented by the formula: wherein the reaction is carried out while an alcohol solution of an alkali metal alkoxide is dropped into the reaction system. A method for producing a compound.

9. General formula (4)

[Wherein, R ² represents a d-6 alkyl group. X represents a halogen atom, a 6 alkyl group or a ₄ haloalkyl group. m represents an integer of 1 to 3. When m is 2 or 3, m Xs may be the same or different. Α-phenyl cyanoacetate compound represented by the general formula (5)

R'OH (5)

[In the formula, R ^1, C ₂ - ₄ alkenyl group, C ₂ - ₄ alkynyl group, (d-6 alkoxy)

C, - ₄ alkyl group, (C, - 4 alkylthio) 4 alkyl group or a benzyl group shown You. ]

Reacting an alcohol compound represented by the general formula (2)

[Wherein, R X and m are the same as above. ]

A method for producing an α-phenyl cyanoacetate compound represented by the formula: wherein the reaction between the α-phenyl cyanoacetate compound of the general formula (4) and the alcohol compound of the general formula (5) is carried out. A general formula (6) formed by a reaction in the presence of at least one catalyst selected from the group consisting of aluminum alkoxides and titanium alkoxides, and

R ² OH (6)

Wherein R ² is the same as above. ]

A method for producing a perfluorocyanoacetic acid ester compound, wherein the alcohol represented by the formula (1) is taken out of the reaction system.