JPH10324672A - Process for producing phenylglyoxylates, process for producing methoxyiminoacetamide derivatives using the same, and intermediates thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for producing phenylglyoxylates, which are important intermediates for the production of agricultural germicides, and to be useful as phenylglyoxylates and agricultural germicides using the same as raw materials. Provided are a method for producing a methoxyiminoacetamide derivative and an intermediate thereof. SOLUTION: General formula (I): [Wherein, A is a benzene ring which may be substituted, and Z is-
O— or —OCH ₂ — or AZ— is a methyl group; X represents a halogen atom], and a Grignard reagent represented by the general formula (II): (COOR ¹ ) ₂ (II) , R ¹ represents n-propyl, n-butyl, isobutyl or sec-butyl], wherein a dialkyl oxalate represented by the general formula (III): [Wherein, A, Z and R ¹ are as defined above].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a process for producing phenylglyoxylates, which are important intermediates for the production of agricultural germicides, and to phenylglyoxylates and agricultural germicides using the same as raw materials. The present invention relates to a method for producing useful methoxyiminoacetamide derivatives, and intermediates thereof.

[0002]

BACKGROUND OF THE INVENTION Phenylglyoxylic amides are known as important intermediates for the production of alkoxyiminoacetamides which are useful as agricultural germicides (Japanese Patent Application Laid-Open No. 3-246268). reference).

[0003] As a production method thereof, for example, a reaction of a phenylglyoxylic halide obtained by reacting an oxalyl halide with a corresponding Grignard reagent and an amine (JP-A-5-97768), or a corresponding carboxylic acid halide and isocyanide Reaction (JP-A-5-33112)
No. 4) is known. However, the economics and safety of oxalyl halide and isocyanide used in these production methods are problems as industrial production methods.

Further, a production method is known in which a phenylglyoxylic acid methyl ester obtained by reacting dimethyl oxalate with a corresponding Grignard reagent in a tetrahydrofuran solvent is reacted with an amine (Japanese Patent Laid-Open No. 3-2).
No. 46268), but this production method was insufficient in the following points.

[0005] 1) Tetrahydrofuran as a solvent in the Grignard reaction step and 1 mol of methanol produced by the reaction are azeotropic, and it is difficult to recover the solvent. This is very problematic as an industrial manufacturing method. 2) Since dimethyl oxalate, which is a raw material of the Grignard reaction step, is a crystal, it is inconvenient as an industrial production method in terms of handling. 3) When the amount of tetrahydrofuran as the solvent is small in the Grignard reaction step, dimethyl oxalate crystals remain, and the amount of by-products increases. This is a problem particularly when a low-temperature reaction is required. 4) In the Grignard reaction step, a large amount of crystals are precipitated as the reaction proceeds, which often makes stirring difficult. This is also a problem when a low-temperature reaction is required. 5) When the intermediate phenylglyoxylic acid methyl esters are amidated without isolation, another mole of methanol produced by the reaction is mixed into the tetrahydrofuran solvent.

The present invention provides an industrially advantageous method for producing phenylglyoxylates which has solved these problems, and is useful as a phenylglyoxylate and agricultural bactericide using it as a raw material. It is an object of the present invention to provide a method for producing a novel methoxyiminoacetamide derivative.

[0007]

Means for Solving the Problems The present inventors have conducted intensive studies in order to find a better method for producing phenylglyoxylic acid amides.
-Propyl esters, n-butyl phenylglyoxylates, isobutyl phenylglyoxylates or sec-butyl phenylglyoxylates to give the desired phenylglyoxylates in high yield and easily. The present invention was completed.

That is, the present invention provides (1) a compound represented by the general formula (I):

[0009]

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Wherein A is a benzene ring which may be substituted, Z is -O- or -OCH _2- , or AZ- is a methyl group; and X is a halogen atom. A dialkyl oxalate represented by the general formula (II): (COOR ¹ ) ₂ (II) wherein R ¹ represents n-propyl, n-butyl, isobutyl or sec-butyl in a tetrahydrofuran solvent Wherein the reaction is carried out in a general formula (III):

[0011]

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Wherein A, Z and R ¹ have the same meanings as defined above, and (2) phenylglyoxylates obtained by the process according to (1). Reacting with an amine represented by the general formula (IV): HNR ² R ³ (IV) wherein R ² and R ³ are the same or different and represent a hydrogen atom, lower alkyl or lower alkoxy. Characteristic, general formula (V):

[0013]

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Wherein A, Z, R²And R^ThreeIs
Phenylglyoxylic amides represented by the same meaning]
Production method of (3) phenylglyoxylates
The method according to (2), wherein the compound is used without isolation, (4)
Phenylglyoxylates were isolated and
Hydrofuran, R ¹OH [wherein R¹Is as defined above)
Performed in the alcohols represented or in a mixed solvent thereof
(2) the production method according to (2), wherein AZ- is a methyl group;
General formula (III) obtained by the production method described in (1)
a):

[0015]

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In the formula, R ¹ is as defined above, and the phenylglyoxylate represented by the general formula (VI) is halogenated.

[0017]

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Wherein X and R ¹ are as defined above, and then a compound of the general formula (VII):

[0019]

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Wherein R ⁴ is a hydrogen atom, lower alkyl,
A lower alkenyl, lower alkoxy, halogenated lower alkyl or halogen atom; n represents an integer of 1 to 4].
b):

[0021]

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Wherein R ¹ , R ⁴ and n are as defined above, to obtain phenylglyoxylates represented by the general formula (IV): HNR ² R ³ (IV) ² and R ³ have the same meanings as defined above).
a):

[0023]

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Wherein R ² , R ³ , R ⁴ and n have the same meanings as described above, and a method for producing phenylglyoxylic amides described in (6), (2) to (5). Wherein methoxylamine or a salt thereof is reacted with phenylglyoxylic acid amides obtained by the production method of the formula (VIII):

[0025]

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Wherein A, Z, R ² and R ³ have the same meanings as described above, and the bond represents a configuration of any of E-form, Z-form or a mixture of E-form and Z-form. (7) A method for producing an iminoacetamide derivative, (7) reacting phenylglyoxylic amides obtained by any one of the production methods described in (2) to (5) with hydroxylamine or a salt thereof to obtain a compound of the general formula (IX) :

[0027]

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Wherein A, Z, R ² , R ³ and a bond
Is the same as defined above), and then reacted with a methylating agent represented by the general formula (X): CH ₃ -L (X) wherein L represents a leaving group. General formula (VIII):

[0029]

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Wherein A, Z, R ² , R ³ and a bond
Is the same as defined above], (8) The method according to any one of (1) to (7), wherein a dialkyl oxalate in which R ¹ is n-butyl is reacted. (9) The production method according to (2) to (7), wherein an amine in which either R ² or R ³ is hydrogen and the other is methyl is reacted, (10) a general formula (III):

[0031]

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Phenylglyoxylates represented by the formula: wherein A, Z and R ¹ are as defined above;
(11) The phenylglyoxylate according to (10), wherein R ¹ is n-butyl, and (12) the general formula (VI):

[0033]

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Wherein X and R ¹ are as defined above.

According to the present invention, di-n-propyl oxalate, di-n-oxalate is reacted with the corresponding Grignard reagent.
-Butyl, diisobutyl oxalate and dise oxalate
Since c-butyl is a liquid and easy to handle, and the dialkyl oxalates and generated phenylglyoxylates are easily soluble in tetrahydrofuran which is a solvent in the Grignard reaction step, the amount of solvent can be reduced. In particular, the fact that n-propyl alcohol, n-butyl alcohol, isobutyl alcohol and sec-butyl alcohol formed in the reaction do not azeotrope with tetrahydrofuran makes it easy to recover the solvent. In the present invention, the Grignard reaction step and the amidation step in tetrahydrofuran solvent may be continuously carried out, or the phenylglyoxylates may be amidated without solvent or in a suitable solvent after isolation. This is an industrially advantageous production method.

The present invention relates to an industrial process for producing a series of production methods as described above, from among a myriad of combinations of various reaction solvents with various raw materials (dialkyl oxalate) or various alcohols produced in the reaction step. One of the combinations that can be practically selected as a standard manufacturing method is specified and provided.

As a separate synthesis of this production method, a compound represented by the general formula (III):

[0038]

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Wherein A, Z and R ¹ are as defined above, wherein AZ- is methyl in the phenylglyoxylates represented by the general formula (IIIa):

[0040]

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In the formula, R ¹ is as defined above, and the phenylglyoxylate is halogenated from the phenylglyoxylate and then phenoxylated, followed by amidation to produce phenylglyoxylate. Can be Therefore, the general formula (VI):

[0042]

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The compound represented by the formula: wherein X and R ¹ have the same meanings as described above, is a novel compound and an important intermediate in this separate synthesis.

Phenylglyoxylic amides can be derived by known methods into methoxyiminoacetamide derivatives useful as agricultural fungicides (Japanese Patent Application Laid-Open No.
-246268). In addition, phenylglyoxylic acid n-propyl ester, phenylglyoxylic acid n
-Butyl esters, phenylglyoxylic acid isobutyl esters and phenylglyoxylic acid sec-butyl esters are novel compounds and important intermediates.

The terms and symbols used in the present specification are described below. The term "lower" as used herein, unless otherwise specified, refers to a group having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. The optionally substituted benzene ring represented by A may be unsubstituted or substituted with the following substituents. For example, lower alkyl (eg, methyl,
Ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.), lower alkenyl (eg, vinyl, allyl, 2-butenyl, etc.), lower alkoxy (eg, methoxy, ethoxy, n-
Propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.), trifluoromethyl and the like. The substituent may be substituted at any position on the benzene ring. The number of the substituents is 1 to 4, preferably 1 to 3, and these may be the same or different. Preferred specific examples of the optionally substituted benzene ring represented by A include:
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,5-dimethylphenyl, 3,4-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, unsubstituted phenyl and the like. Can be

Z represents —O—, —OCH ₂ —, or AZ
-Is defined as a methyl group. R ¹ is defined as n-propyl, n-butyl, isobutyl or sec-butyl. Of these, n-butyl is preferred. R
² , R ³ are the same or different and are defined as a hydrogen atom, lower alkyl or lower alkoxy. As the lower alkyl represented by R ² and R ³ , the same as those exemplified as the lower alkyl which may be substituted on the benzene ring represented by A are mentioned. Examples of the lower alkoxy represented by R ² and R ³ include the same as those exemplified as the lower alkoxy which may be substituted on the benzene ring represented by A. Particularly preferred in these cases is when either R ² or R ³ is hydrogen and the other is methyl.

R ⁴ is, for example, lower alkyl (eg, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.), lower alkenyl (eg, vinyl, allyl, -Butenyl, etc.), lower alkoxy (eg, methoxy, ethoxy,
n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc., lower alkyl halides (eg, trifluoromethyl, trichloromethyl, difluoromethyl, chloromethyl, 2-bromoethyl, 1,2 -Dichloropropyl, etc.), halogen atoms (eg, fluorine atom, chlorine atom, bromine atom, iodine atom) and the like. The substituent may be substituted at any position on the benzene ring. The number n of the substituents is 1 to 4, preferably 1 to 3, and these may be the same or different. Preferred specific examples of R ⁴ include 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, and 3-chlorophenyl.
Methylphenyl, 4-methylphenyl, 2,5-dimethylphenyl, 3,4-dimethylphenyl, 4-chloro-
2-methylphenyl, 3,4-dichlorophenyl, 3-
Trifluoromethylphenyl, 4-trifluoromethylphenyl, unsubstituted phenyl and the like.

As the halogen atom represented by X, the same as those exemplified above as the halogen atom for the substituent represented by R ⁴ can be mentioned. The compounds represented by the general formulas (VIII) and (IX) have E by an imino moiety.
There are two types of isomers, Z-isomer and Z-isomer.
It includes these isomers and mixtures of these isomers in any ratio. In this specification, a wavy line (~) is used in the general formula.
To illustrate this. As the leaving group represented by L,
Examples include a halogen atom (eg, a chlorine atom, a bromine atom, an iodine atom, etc.) and methoxysulfonyloxy.

[0049]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the production method of the present invention will be described below for each step. [Step 1]

[0050]

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[Wherein the symbols have the same meanings as described above. That is, the Grignard reagent (I) can be produced by reacting a halide (XI) with magnesium in dry tetrahydrofuran. Usually, 1 to 4 equivalents, preferably 1 to 2 equivalents of magnesium are reacted with the halide (XI). The amount of tetrahydrofuran to be used is generally about 1 to halide (XI).
10 to 10 times by weight. The reaction temperature is usually from 20 ° C to the reflux temperature of the reaction mixture, preferably from 30 to 85 ° C. The reaction time is 10 minutes to 24 hours, preferably 30 minutes to 10 hours. If necessary, iodine as an activator of the reaction,
A small amount of 1,2-dibromoethane, ethyl bromide or the like is used. Further, Grignard reagent (I) itself may be used as the activator. The amount thereof is 0.001 to 0.4 equivalent, preferably 0.005 to 0.2 equivalent, relative to (XI) of the halide. The Grignard reagent (I) thus obtained may be isolated, but can usually be used in the next step as a reaction solution.

[Step 2]

[0053]

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[Wherein each symbol has the same meaning as described above] That is, the phenylglyoxylate represented by the general formula (III) is obtained by converting a Grignard reagent (I) and a dialkyl oxalate (II) in tetrahydrofuran. It can be produced by reacting. In the reaction, usually, a solution of the Grignard reagent (I) in tetrahydrofuran is dropped into a solution of dialkyl oxalate (II) dissolved in about 1 to 10 times by weight of tetrahydrofuran. Dialkyl oxalate (I
I) uses any of di-n-propyl oxalate, di-n-butyl oxalate, diisobutyl oxalate, and disec-butyl oxalate, and is 1 to Grignard reagent (I).
Equivalent or more, preferably 1 to 3 equivalents can be used. Dropping is -100 to 50C, preferably -8.
The reaction is performed at 0 to 30 ° C for 5 minutes to 5 hours, preferably for 15 minutes to 3 hours. Then, if necessary, the reaction may be carried out at -100 to 50C, preferably at -80 to 30C, for 30 minutes to 5 hours. Alternatively, the reaction may be carried out by diluting dialkyl oxalate (II) in a tetrahydrofuran solution of the Grignard reagent (I) with about 1 to 10 times by weight of tetrahydrofuran, or by adding dropwise without dilution. The reaction conditions are the same as described above. The obtained phenylglyoxylates (III) can be used in the next step after being purified as a reaction solution or as a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.).

Phenylglyoxylates (II)
I) is a novel compound and is included in the present invention. Among the compounds represented by this general formula, it is preferred that R ¹ is n-butyl.

[Step 3]

[0057]

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[Wherein the symbols have the same meanings as described above] That is, the phenylglyoxylate represented by the general formula (V) is a phenylglyoxylate (II)
It can be produced by reacting I) with an amine (IV) without solvent or in a suitable solvent (single or mixed). The reaction can be carried out under normal pressure or under pressure. Examples of the amine (IV) include primary amines (eg, methylamine, ethylamine, n-propylamine, methoxylamine, etc.), secondary amines (eg, dimethylamine, diethylamine, methylethylamine, di-n-propylamine, etc.) and ammonia Is mentioned. The amount of the amine (IV) to be used varies depending on whether the phenylglyoxylate (III) is used without isolation or is isolated and used, but usually the phenylglyoxylate (III) is used.
Can be used in an amount of 1 to 12 equivalents, preferably 1 to 8 equivalents. The amine (IV) may be diluted with a solvent and added dropwise to the phenylglyoxylates (IV), or when the amine (IV) is liquid, it may be added without dilution with the solvent. When the amine (IV) is a gas, it may be directly introduced into the reaction solution.

Examples of the solvent for diluting the amine (IV) with a solvent include hydrocarbons (eg, benzene, toluene, xylene, etc.) and halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, etc.). ), Ethers (eg, tetrahydrofuran, dioxane, etc.), alcohols (eg, methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.), water, and a mixed solvent thereof. In particular, alcohols (n-propanol, n-butanol, isobutanol, sec-butanol), water, a mixed solvent thereof and the like generated by the reaction are preferred. When the phenylglyoxylates (III) are used without isolation, they are reacted without adding a new solvent, or, if necessary, exemplified as a solvent for diluting the amine (IV) with the solvent. The reaction may be carried out by diluting with the same solvent as described above. When the isolated phenylglyoxylates (III) are used, examples of the reaction solvent include the same solvents as those exemplified as the solvent when the amine (IV) is diluted with the solvent. Particularly, tetrahydrofuran, alcohols produced by the reaction (n-propanol, n-butanol, isobutanol, sec-butanol), and a mixed solvent thereof are preferable. The dropwise addition and introduction of the amine (IV) are carried out at -75 to 60C, preferably at -30 to 40C.
The reaction is performed for 5 minutes to 12 hours, preferably for 30 minutes to 6 hours. Then, the reaction is carried out at -50 to 100 ° C, preferably 0 to 60 ° C, for 1 minute to 24 hours, preferably 30 minutes to 12 hours to obtain phenylglyoxylic acid amides (V).
The obtained phenylglyoxylic amides (V) can be used in the next step after being purified as a reaction solution or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.).

[Step 4]

[0061]

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[Wherein the symbols have the same meanings as described above] That is, the methoxyiminoacetamides represented by the general formula (VIII) are obtained by adding methoxylamine or a salt thereof to phenylglyoxylic amides (V). It can be produced by reacting in a solvent (single or mixed).
Methoxylamine or a salt thereof is used in an amount of 1 to 4 equivalents, preferably 1 equivalent, based on the phenylglyoxylic acid amide (V).
~ 2.5 equivalents can be used. Examples of the salt of methoxylamine include mineral salts such as hydrochloride and sulfate. Examples of the solvent that can be used include hydrocarbons (eg, benzene, toluene, xylene, etc.), halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, etc.), ethers (eg, tetrahydrofuran,
Dioxane), alcohols (eg, methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.), water, and a mixed solvent thereof. The reaction temperature is 0 to 160 ° C, preferably 20 to 13 ° C.
0 ° C. The reaction time is usually about 15 minutes to 24 hours. The obtained desired methoxyiminoacetamides (VIII) can be purified by a conventional method (eg, column chromatography, recrystallization, etc.) if necessary. In addition, desired methoxyiminoacetamides (VIII)
Follows the general formula (I) according to the following steps 5 and 6.
It can be produced via hydroxyiminoacetamides represented by X).

[Step 5]

[0064]

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Wherein each symbol has the same meaning as described above. That is, hydroxyiminoacetamides (IX) are prepared by adding phenylglyoxylic amides (V) to hydroxylamine or a salt thereof in a suitable solvent (single Or mixed),
It can be produced by reacting. Hydroxylamine or a salt thereof is a phenylglyoxylic acid amide (V)
Can be used in an amount of 1 to 4 equivalents, preferably 1 to 2.5 equivalents. Examples of the hydroxylamine salt include mineral salts such as hydrochloride and sulfate. Examples of the solvent that can be used include hydrocarbons (eg, benzene, toluene, xylene, etc.), halogenated hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, etc.),
Ethers (eg, tetrahydrofuran, dioxane, etc.), alcohols (eg, methanol, ethanol, n
-Propanol, isopropanol, n-butanol, etc.), water, and a mixed solvent thereof. The reaction temperature is 0 to 160C, preferably 20 to 130C. The reaction time is usually about 15 minutes to 24 hours.
The obtained hydroxyiminoacetamides (IX)
The reaction solution can be used as it is, as a crude product, or purified by a conventional method (eg, column chromatography, recrystallization, etc.) and used in the next step.

[Step 6]

[0067]

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[Wherein, L represents a leaving group such as a halogen atom (eg, chlorine atom, bromine atom, iodine atom) or methoxysulfonyloxy, and other symbols have the same meanings as described above]. The methoxyiminoacetamides represented by the formula (VIII) include hydroxyiminoacetamides (I
X) and compound (X) can be produced by reacting in a suitable solvent (single or mixed) in the presence of a base. Examples of the compound (X) which is a methylating agent include dimethyl sulfate, methyl halide (eg, methyl chloride, methyl bromide, methyl iodide) and the like. In this reaction, compound (X)
Can be used in an amount of 1 equivalent or more, preferably 1 to 3 equivalents, to hydroxyiminoacetamides (IX). Examples of the base that can be used include metal hydroxides (eg, sodium hydroxide, potassium hydroxide, etc.), metal carbonates (eg, sodium carbonate, potassium carbonate, etc.), metal alkoxides (eg, sodium methoxide). , Sodium ethoxide, potassium tert-butoxide, etc.) and the like, and it can be used in an amount of 1 equivalent or more, preferably 1 to 3 equivalents, relative to compound (IX). Examples of usable solvents include, for example, N, N-
Dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.),
Saturated hydrocarbons (eg, cyclohexane, hexane, etc.),
Halogenated hydrocarbons (eg, dichloromethane, 1,2-
Examples thereof include dichloroethane, etc.), ethers (eg, tetrahydrofuran, dioxane, etc.), ketones (eg, acetone, methyl ethyl ketone, etc.), nitriles (eg, acetonitrile, etc.), water, and a mixed solvent thereof. The reaction temperature is -30 to 150C, preferably -10 to 100C.
It is. The reaction time varies depending on the compound, but is from 30 minutes to 70 minutes.
The reaction may be performed for a time. The obtained desired methoxyiminoacetamides (VIII) can be purified by a conventional method (eg, chromatography, recrystallization, etc.) if necessary.

[Step 7]

[0070]

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[Wherein the symbols have the same meanings as described above] That is, the compound represented by the general formula (VI) is represented by the general formula (I
It can be produced by halogenating the methyl group of the benzene ring of the phenylglyoxylate represented by IIa). For example, in a solvent such as carbon tetrachloride, cyclohexane, benzene, or chlorobenzene, chlorine, bromine, a halogenating agent such as N-chlorosuccinimide or N-bromosuccinimide and, if necessary, under light irradiation using a mercury lamp. It can be produced by reacting or reacting in the presence of a radical initiator such as 2,2'-azobis (isobutylylonitrile) and dibenzoyl peroxide. In this reaction, the halogenating agent is used in an amount of 1 equivalent or more relative to the phenylglyoxylates (IIIa),
Preferably, 1 to 1.5 equivalents can be used. Radical initiators include phenylglyoxylates (I
0.01 equivalent or more, preferably 0.03 to 0.5 equivalent, can be used relative to IIa). The reaction temperature is from 20 to 120C, preferably from 50 to 90C. The reaction time varies depending on the compound, but the reaction may be carried out for 5 minutes to 3 hours. The obtained compound (VI) can be used in the next step as it is as a reaction solution or as a crude product, or purified by a conventional method (eg, column chromatography, recrystallization, etc.). Compound (VI) is a novel compound and is included in the present invention.

[Step 8]

[0073]

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[Wherein the symbols have the same meanings as described above] That is, the phenylglyoxylate represented by the general formula (IIIb) is obtained by combining the compound (VI) with the general formula (VI)
It can be produced by reacting the phenols represented by I) in the presence of a base without solvent or in a suitable solvent (single or mixed). In this reaction, phenols (V
II) can be used in an amount of 1 equivalent or more, preferably 1 to 2 equivalents, relative to compound (VI). Examples of the base that can be used include metal hydroxides (eg, sodium hydroxide, potassium hydroxide, etc.), metal carbonates (eg, sodium carbonate, potassium carbonate, etc.), metal alkoxides (eg, sodium methoxide). , Sodium ethoxide, potassium tert-butoxide, etc.), metal hydrides (eg, sodium hydride, potassium hydride, etc.) and the like, and the base is 1 equivalent or more, preferably 1 equivalent to compound (VI). ~ 3 equivalents can be used. Examples of usable solvents include N, N-dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons (eg, toluene, benzene, xylene, etc.), saturated hydrocarbons (eg, cyclohexane, hexane, etc.), ethers ( Examples thereof include tetrahydrofuran, dioxane, etc., ketones (eg, acetone, methyl ethyl ketone, etc.), nitriles (eg, acetonitrile, etc.), water, and a mixed solvent thereof. The reaction temperature is -20 to 130 ° C,
Preferably it is 0-100 degreeC. The reaction time varies depending on the compound, but the reaction may be carried out for 10 minutes to 24 hours. The obtained phenylglyoxylates (IIIb)
The reaction solution can be used as it is, as a crude product, or purified by a conventional method (eg, column chromatography, recrystallization, etc.) and used in the next step.

[Step 9]

[0076]

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[Wherein the symbols have the same meanings as described above] That is, the phenylglyoxylic amide represented by the general formula (Va) is obtained by adding an amine ( IV) under the same conditions as in step 3 to produce the compound. The resulting phenylglyoxylic amides are (V
a) can be used in the next step after purification as a reaction solution or a crude product, or by a conventional method (eg, column chromatography, recrystallization, etc.). The methoxyiminoacetamide derivative represented by the general formula (VIII) obtained by the above Steps 4 and 6 has excellent bactericidal activity and is useful as an agricultural germicide (Japanese Patent Laid-Open No. 3-2).
46268).

[0078]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. The ¹ H-NMR value described in the examples is 270 in deuterated chloroform using tetramethylsilane as an internal standard.
It was measured in MHz, and the chemical shift value was represented by δ (ppm). Coupling constants (J) are given in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, m is a multiplet, and brs is a wide singlet.

Example 1 Production of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide 1.34 g (55 mm) of magnesium under a nitrogen gas atmosphere
ol), 14.56 g (50 mmol) of 1-bromo-2- (2,5-dimethylphenoxymethyl) benzene was dissolved in 10 ml of dry tetrahydrofuran in a mixture of 25 ml of dry tetrahydrofuran and 0.19 ml (2.5 mmol) of ethyl bromide. A small amount of the solution was added dropwise and heated, and after the formation of the Grignard reagent started, the remaining solution was heated to an internal temperature of 5 ° C.
The solution was added dropwise over 30 minutes while maintaining the temperature at 0 to 60 ° C. Then 5
After stirring at 0 to 60 ° C. for 1 hour, the mixture was cooled to room temperature. The reaction solution was transferred to a dropping funnel using 6 ml of dry tetrahydrofuran, and 15.17 g of di-n-butyl oxalate (75 m
mol) was added dropwise to a solution of 50 ml of dry tetrahydrofuran at −10 to 0 ° C. over 30 minutes. After washing the dropping funnel with 4 ml of dry tetrahydrofuran, the mixture was stirred at -10 to 0 ° C for 1 hour. 4
17.2 ml of 0% methylamine aqueous solution (200 mmo
l) was added and the mixture was stirred at room temperature for 1 hour. After the reaction, 100 ml of a 2N aqueous hydrochloric acid solution was added, and the mixture was stirred for 15 minutes, extracted with 150 ml of ethyl acetate, washed three times with 150 ml of water, further washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 2- [2- Crude crystals of (2,5-dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide were obtained. The crystals were purified by silica gel chromatography (ethyl acetate / n-hexane / dichloromethane) to obtain 9.67 g (yield: 65.0%) of crystals. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.16 (3H, s), 2.31 (3H, s), 2.8
0 (3H, d, J = 4.9), 5.29 (2H, s), 6.69-7.99 (8H, m).

[Example 2] 2- (2-phenoxyphenyl) -2-oxoacetic acid n-
Production of butyl 20.46 g of 2-chlorodiphenyl ether (100 m
mol) in 20 ml of dry tetrahydrofuran,
The reaction was started by adding 3.16 g (130 mmol) of magnesium and 0.75 ml (10 mmol) of ethyl bromide, and the reaction started. When the temperature was adjusted with ice water so that the internal temperature became 70 to 80 ° C., the heat generation was reduced in about 30 minutes. An additional 20 ml of dry tetrahydrofuran was added, and the mixture was heated in an oil bath at 80 ° C for 6 hours (internal temperature: 72 to 73 ° C). After cooling the reaction solution to room temperature, it was transferred to a dropping funnel with 30 ml of dry tetrahydrofuran, and 22.25 g of di-n-butyl oxalate (110 m
mol) was added dropwise to a solution of 30 ml of dry tetrahydrofuran at −10 to −5 ° C. over 1 hour. Subsequently, the mixture was stirred at −10 to −5 ° C. for 1 hour, and further stirred at room temperature for 2 hours. After the reaction, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted three times with 100 ml of ether, and washed with saturated saline.
Dry over anhydrous magnesium sulfate and concentrate under reduced pressure to give crude 2-
32.34 g of n-butyl (2-phenoxyphenyl) -2-oxoacetate was obtained. The purity was 82.3% (HPLC quantification), and the conversion yield was 88.9%. A part of the crude product was repeatedly purified by silica gel chromatography (toluene / n-hexane and ethyl acetate / n-hexane) to obtain pale yellow crystals having a low melting point. ¹ H-NMR (CDCl ₃ ) δppm: 0.81 (3H, t, J = 7.3), 1.22-1.36
(2H, m), 1.48-1.58 (2H, m), 4.12 (2H, t, J = 7.3), 6.8
6 (1H, d, J = 8.8), 7.07-7.55 (7H, m), 7.98 (1H, d, J =
7.8).

[Example 3] 2- (2-phenoxyphenyl) -2-oxoacetic acid n-
Production of butyl 20.46 g of 2-chlorodiphenyl ether (100 m
mol) in 20 ml of dry tetrahydrofuran,
The reaction was started by adding 3.16 g (130 mmol) of magnesium and 0.75 ml (10 mmol) of ethyl bromide, and the reaction was started. When the temperature was adjusted with ice water so that the internal temperature became 70 to 80 ° C., the heat generation was reduced in about 30 minutes. 20 ml of dry tetrahydrofuran was added, and the mixture was heated in an oil bath at 80 ° C. for 3 hours (internal temperature 70 to 72 ° C.). After cooling the reaction solution to room temperature, it was transferred to a dropping funnel with 30 ml of dry tetrahydrofuran, and 22.25 g of di-n-butyl oxalate (110 m
mol) was added dropwise to a solution of 30 ml of dry tetrahydrofuran at 5-10 ° C. over 1 hour. Then 5
After stirring at ℃ for 1 hour, the mixture was further stirred at room temperature for 2 hours. After the reaction, a saturated aqueous solution of ammonium chloride was added to add ether 10
The mixture was extracted three times with 0 ml, washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 32.27 g of crude n-butyl 2- (2-phenoxyphenyl) -2-oxoacetate. Purity 78.7% (HPLC quantification), reduced yield 85.
1%.

Example 4 Production of 2- (2-phenoxyphenyl) -2-oxo-N-methylacetamide 2- (2-phenoxyphenyl) -2-oxoacetic acid n-
597 mg (2 mmol) of butyl was added to 2 m of n-butanol.
in a 40% aqueous methylamine solution under ice-cooling.
9 ml (5 mmol) were added. After stirring at room temperature for 1.5 hours, the mixture was concentrated under reduced pressure, 30 ml of water was added to the residue, and the mixture was extracted twice with 30 ml of toluene, washed with 20 ml of water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 2- (2-phenoxyphenyl). Crude crystals of -2-oxo-N-methylacetamide were obtained. The crystals were purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 480 mg (yield 94.0%) of crystals. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.87 (3H, d, J = 4.9), 6.63 (1H,
brs), 6.86-7.78 (9H, m).

Example 5 Preparation of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-methoxyimino-N-methylacetamide 2- [2- (2,5-dimethylphenoxymethyl) Phenyl] -2-oxo-N-methylacetamide 0.27
2 ml of methanol and 0.15 g (1.8 mmol) of methoxylamine hydrochloride were added to g (0.9 mmol), and the mixture was heated under reflux for 4 hours. After the reaction, 100 ml of water was added, extracted twice with methylene chloride, and dried over anhydrous magnesium sulfate. After drying, the mixture is concentrated under reduced pressure to give a mixture of E-form and Z-form of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-methoxyimino-N-methylacetamide (about 1: 1). 0.28 g (yield 98.9%) was obtained. ¹ H-NMR (CDCl ₃ ) δ ppm: 3.95 (1.5 H, s), 4.01 (1.5 H, s),
4.92 (1H, s), 5.17 (1H, s).

Example 6 Production of 2- (2-phenoxyphenyl) -2-hydroxyimino-N-methylacetamide 1.28 g (5 mmol) of 2- (2-phenoxyphenyl) -2-oxo-N-methylacetamide ) In 10 ml of methanol and 0.69 g of hydroxylamine hydrochloride (10
mmol) and heated to reflux for 13.5 hours. After the reaction, 150 ml of saline was added and 150 ml of methylene chloride was added.
And dried over anhydrous magnesium sulfate. After drying,
Concentrate under reduced pressure to give 2- (2-phenoxyphenyl) -2
1.33 g (yield 97.8) of a mixture of E-form and Z-form of -hydroxyimino-N-methylacetamide (about 99: 1)
%). Melting point 183-184.5 [deg.] C. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.84 (3H, d, J = 4.9), 6.77 (1H,
brs), 6.88-7.37 (9H, m).

Example 7 Production of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-hydroxyimino-N-methylacetamide 2- [2- (2,5-dimethylphenoxymethyl) Phenyl] -2-oxo-N-methylacetamide 11.9
To 0 g (40 mmol), 120 ml of ethanol and 5.56 g (80 mmol) of hydroxylamine hydrochloride were added,
The mixture was heated under reflux for 13 hours. After the reaction, 400 ml of saline was added, extracted twice with 200 ml of methylene chloride, and dried over anhydrous magnesium sulfate. After drying, the crystals obtained by concentration under reduced pressure were recrystallized from ethyl acetate / n-hexane to give (E) -2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-hydroxyimino. 5.58 g (yield 44.7%) of crystals of -N-methylacetamide were obtained. Further, the mother liquor of the recrystallization was purified by silica gel chromatography (ethyl acetate / n-hexane) to give (E)
3.59 g of crystals of -2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-hydroxyimino-N-methylacetamide (28.7% yield) and (Z) -2
3.25 g (yield: 26.0%) of crystals of-[2- (2,5-dimethylphenoxymethyl) phenyl] -2-hydroxyimino-N-methylacetamide were obtained. E-form: melting point 154 to 155.5 ° C. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.17 (3H, s), 2.29 (3H, s), 2.8
6 (3H, d, J = 4.9), 4.96 (2H, s), 6.64-7.61 (8H, m). Z form: melting point: 139 to 141 ° C. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.15 (3H, s) ), 2.31 (3H, s), 2.7
7 (3H, d, J = 4.9), 5.06 (2H, s), 5.79 (1H, brs), 6.69-
7.68 (7H, m).

Example 8 Preparation of (E) -2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-methoxyimino-N-methylacetamide (E) -2- [2- ( 2,5-dimethylphenoxymethyl) phenyl] -2-hydroxyimino-N-methylacetamide to 6.25 g (20 mmol) of acetone 60
Then, 8.29 g (60 mmol) of potassium carbonate and 3.78 ml (40 mmol) of dimethyl sulfate were added, and the mixture was stirred at room temperature for 14 hours. After the reaction, insolubles were removed, and the residue obtained by concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate / n-hexane) to give (E) -2.
6.12 g (yield 93.7%) of crystals of-[2- (2,5-dimethylphenoxymethyl) phenyl] -2-methoxyimino-N-methylacetamide were obtained. Melting point 136
~ 137 ° C. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.18 (3H, s), 2.29 (3H, s), 2.8
8 (3H, d, J = 4.9), 3.95 (3H, s), 4.92 (2H, s), 6.62-7.
57 (8H, m).

Example 9 Preparation of (E) -2- (2-phenoxyphenyl) -2-methoxyimino-N-methylacetamide (E) -2- (2-phenoxyphenyl) -2-hydroxyimino- 0.54 g of N-methylacetamide (2 m
mol), acetone 6ml, potassium carbonate 0.83g
(6 mmol) and 0.38 ml of dimethyl sulfate (4 mmo)
l) was added and the mixture was stirred at room temperature for 65 hours. After the reaction, insolubles were removed, and the residue obtained by concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate / n-hexane) to give (E) -2- (2-phenoxyphenyl) -2
Crystal of -methoxyimino-N-methylacetamide
54 g (94.7% yield) was obtained. 83-84 ° C. ¹ H-NMR (CDCl ₃ ) δ ppm: 2.87 (3H, d, J = 4.9), 3.91 (3H,
s), 6.63 (1H, brs), 6.88-7.36 (9H, m).

Example 10 Production of n-butyl 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxoacetate 0.30 g (12.3) of magnesium under a nitrogen gas atmosphere
mmol), 4 ml of dry tetrahydrofuran and 0.05 ml (0.7 mmol) of ethyl bromide in a mixture of 2.91 g (10.0 mmol) of 1-bromo-2- (2,5-dimethylphenoxymethyl) benzene in 10 ml of dry tetrahydrofuran. A small amount of the dissolved solution is dropped and heated,
After the formation of the Grignard reagent started, the remaining solution was added dropwise over 10 minutes while maintaining the internal temperature at 50 ° C. or lower, followed by 5 minutes.
Stirred at 0 ° C. for 1 hour. After cooling the reaction to room temperature,
3.03 g (15.0 mmol) of di-n-butyl oxalate
Was dissolved in 10 ml of dry tetrahydrofuran.
The solution was added dropwise at 30 to -20 ° C over 10 minutes. Subsequently, the mixture was stirred at −30 to −20 ° C. for 1 hour. After the reaction, a saturated aqueous solution of ammonium chloride was added, and the mixture was stirred for 10 minutes, extracted three times with 30 ml of ether, washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain crude 2- [2- (2,5
[Dimethylphenoxymethyl) phenyl] -2-oxoacetate was obtained. The crude product was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 1.91 g (yield: 56.2%) of colorless crystals. Melting point 64 ~
67 ° C. _{^{1 H-NMR (CDCl 3)}} δppm: 0.93 (3H, t, J = 7.3), 1.32-1.46
(2H, m), 1.61-1.75 (2H, m), 2.26 (3H, s), 2.31 (3H,
s), 4.26 (2H, t, J = 7.3), 5.39 (2H, s), 6.70 (1H, d, J
= 7.6), 6.72 (1H, s), 7.04 (1H, d, J = 7.6), 7.46 (1H,
t, J = 7.9), 7.66 (1H, t, J = 7.9), 7.82 (1H, d, J = 7.9),
7.84 (1H, d, J = 7.9).

Example 11 Preparation of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide 2- [2- (2,5-dimethylphenoxymethyl) phenyl 1.00 g of n-butyl-2-oxoacetate (2.9
4 mmol) was dissolved in 5 ml of methanol, and 0.60 g (7.7 mmol) of a 40% methylamine methanol solution was dissolved.
Was added and reacted at room temperature for 4 hours.

After the reaction, the mixture was concentrated under reduced pressure to give 2- [2- (2,5
-Dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide (0.90 g) was obtained.

Example 12 Production of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide Magnesium 0.67 g (27.5) in a nitrogen gas atmosphere
mmol), 3 ml of dry tetrahydrofuran and 1,2-
A solution of 7.28 g (25 mmol) of 1-bromo-2- (2,5-dimethylphenoxymethyl) benzene in 20 ml of dry tetrahydrofuran was added dropwise to a mixture of 0.11 ml (1.3 mmol) of dibromoethane and heated. After the generation of the Grignard reagent was started, the remaining solution was added dropwise over 15 minutes while maintaining the internal temperature at 50 to 60 ° C. Subsequently, the mixture was stirred at 60 ° C. for 1 hour, and then cooled to room temperature. The reaction solution was transferred to a dropping funnel using 2 ml of dry tetrahydrofuran, and 10.21 ml of di-n-butyl oxalate was added.
(50 mmol) was added dropwise to a solution of 45 ml of dry tetrahydrofuran at −65 to −60 ° C. over 20 minutes. The dropping funnel is dried with 5 ml of tetrahydrofuran
Then, the mixture was stirred at -60 ° C for 1 hour. After the reaction, 100 ml of ammonium chloride aqueous solution and 100 ml of toluene
After stirring at room temperature for 5 minutes, the toluene layer and the aqueous layer were separated. The aqueous layer was further extracted with 100 ml of toluene,
The combined toluene layers were washed with 100 ml and 200 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give crude 2
17.72 g of n-butyl 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxoacetate was obtained. This crude product was dissolved in 25 ml of methanol, 9.71 g (125 mmol) of a 40% methylamine methanol solution was added under ice cooling, and the mixture was stirred at room temperature overnight. After the reaction, 200
The mixture was adjusted to pH 2 or less with concentrated hydrochloric acid, extracted twice with 200 ml of toluene, washed with 200 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain crystals obtained from ethyl acetate / n-hexane. After recrystallization, 2- [2-
(2,5-dimethylphenoxymethyl) phenyl] -2
4.58 g of -oxo-N-methylacetamide (yield 6)
1.6%). Further, the recrystallized mother liquor was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 0.52 g (yield 7.0%) of crystals.

Example 13 Production of n-butyl 2- (2-methylphenyl) -2-oxoacetate 2.91 g (0.12 g) of magnesium under a nitrogen gas atmosphere
mol), a solution of 17.10 g (0.10 mol) of 2-bromotoluene in 50 ml of dry tetrahydrofuran was added dropwise to a mixture of 10 ml of dry tetrahydrofuran and 0.04 ml (0.5 mmol) of ethyl bromide, and the mixture was heated. After the formation of the Grignard reagent has started, the remaining solution is added dropwise over 20 minutes while maintaining the internal temperature at 50 ° C. or lower,
Subsequently, the mixture was stirred at 50 ° C. for 1 hour. After the reaction solution was cooled to room temperature, 26.30 g of di-n-butyl oxalate (0.13 g
mol) was added dropwise to a solution of 100 ml of dry tetrahydrofuran at −78 ° C. over 40 minutes. Subsequently, the mixture was stirred at -78 ° C for 1 hour. After the reaction, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted three times with 100 ml of ether, washed with saturated saline, and dried over anhydrous magnesium sulfate.
After concentration under reduced pressure, crude n-butyl 2- (2-methylphenyl) -2-oxoacetate was obtained. ¹ H-NMR (CDCl ₃ ) δ ppm: 0.96 (3H, t, J = 7.3), 1.40-1.48
(2H, m), 1.72-1.78 (2H, m), 2.61 (3H, s), 4.37 (2H, m
t, J = 7.3), 7.31 (2H, t, J = 7.6), 7.45 (1H, t, J = 7.6),
7,68 (1H, d, J = 7.6).

Example 14 2- (2-bromomethylphenyl) -2-oxoacetic acid n
Preparation of -butyl 5.00 g of crude n-butyl 2- (2-methylphenyl) -2-oxoacetate obtained in Example 13 (22.7
mmol) in 20 ml of benzene, 4.44 g (25.0 mmol) of N-bromosuccinimide and 2,2
0.15 g of 2'-azobis (isobutylylonitrile)
(0.9 mmol) was added and the mixture was heated under reflux for 3 hours. After the reaction solution was cooled to remove insolubles, the residue obtained by concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate / n-hexane) to give 2- (2-bromomethylphenyl) -2. -5.20 g of n-butyl oxoacetate
(76.6% yield) as an oil.

¹ H-NMR (CDCl ₃ ) δ ppm: 0.93 (3H, t, J = 7.
3), 1.40-1.49 (2H, m), 1.71-1.80 (2H, m), 4.39 (2H, m
t, J = 7.3), 4.90 (2H, s), 7.44-7.48 (1H, m), 7.56-7.6
0 (2H, m), 7.73 (1H, d, J = 8.6).

Example 15 Preparation of 2- [2- (2,5-dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide 2- (2-bromomethylphenyl) -2-oxoacetic acid n
Butyl (2.00 g, 6.7 mmol) was dissolved in N, N-dimethylformamide (6 ml), 2,5-xylenol (0.98 g, 8.0 mmol) and potassium carbonate (1.8).
4 g (13.3 mmol) was added and the mixture was stirred at room temperature for 3 hours. After the reaction, add 40 ml of water and add 100 ml of ether.
Extracted three times, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (ethyl acetate / n-hexane) to give 2- [2- (2,5 -Dimethylphenoxymethyl) phenyl] -2-oxo-N-methylacetamide (1.20 g, yield 52.6%) was obtained.

[0096]

According to the present invention, n-propyl alcohol, n-butyl alcohol, isobutyl alcohol and sec-butyl alcohol produced in the Grignard reaction step do not azeotrope with the reaction solvent tetrahydrofuran, so that the solvent can be easily recovered. . Further, di-n-propyl oxalate, di-n-butyl oxalate, diisobutyl oxalate and disec-butyl oxalate reacted with the corresponding Grignard reagent are liquid and easy to handle, and their dialkyl oxalates are used. And the resulting phenylglyoxylate are easily soluble in tetrahydrofuran, which is a solvent in the Grignard reaction step, so that the amount of solvent can be reduced.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 69/738 C07C 69/738 Z 231/02 231/02 235/78 235/78

Claims (12)

[Claims] 1. A compound of the general formula (I): [Wherein, A is a benzene ring which may be substituted, and Z is-
O— or —OCH ₂ — or AZ— is a methyl group; X represents a halogen atom], and a Grignard reagent represented by the general formula (II): (COOR ¹ ) ₂ (II) , R ¹ represents n-propyl, n-butyl, isobutyl or sec-butyl], wherein a dialkyl oxalate represented by the general formula (III): [Wherein, A, Z and R ¹ are as defined above]. 2. A phenylglyoxylate obtained by the production method according to claim 1, which has the general formula (IV): HNR ² R ³ (IV) wherein R ² and R ³ are the same or different. A hydrogen atom, a lower alkyl or a lower alkoxy]], which is represented by the general formula (V): [Wherein A, Z, R ² and R ³ are as defined above]. 3. The process according to claim 2, wherein the phenylglyoxylate is used without isolation. 4. The method according to claim 2, wherein the phenylglyoxylate is isolated and the reaction is carried out in tetrahydrofuran, an alcohol represented by R ¹ OH (where R ¹ is as defined above), or a mixed solvent thereof. The production method described in 1. 5. The general formula (IIIa) obtained by the production method according to claim 1, wherein AZ- is a methyl group. [Wherein R ¹ has the same meaning as above] by halogenating a phenylglyoxylate represented by the general formula (V
I): Wherein X and R ¹ are as defined above, and then a compound represented by the general formula (VII): Wherein R ⁴ is a hydrogen atom, lower alkyl, lower alkenyl, lower alkoxy, halogenated lower alkyl or halogen atom; n is an integer of 1 to 4; Formula (IIIb): Wherein R ¹ , R ⁴ and n are as defined above, to obtain a phenylglyoxylate represented by the general formula (IV): HNR ² R ³ (IV) wherein R ² and R ³ is the same as defined above), and the amine represented by the general formula (V
a): embedded image [Wherein R ² , R ³ , R ⁴ and n are as defined above]. 6. A general formula (VIII) characterized by reacting methoxylamine or a salt thereof with phenylglyoxylic acid amides obtained by the production method according to any one of claims 2 to 5. Embedded image [Wherein A, Z, R ² and R ³ have the same meanings and bonding as described above]
Represents a configuration of any of E-form, Z-form and a mixture of E-form and Z-form]. 7. A phenylglyoxylic amide obtained by any one of claims 2 to 5 is reacted with hydroxylamine or a salt thereof to give a compound of the general formula (IX): Wherein A, Z, R ² , R ³ and the bond は are the same as defined above, to obtain a hydroxyiminoacetamide derivative represented by the general formula (X): CH ₃ -L (X) L represents a leaving group], wherein a methylating agent represented by the following general formula (VIII): Wherein A, Z, R ² , R ³ and the bond are as defined above. 8. The method according to claim 1, wherein a dialkyl oxalate wherein R ¹ is n-butyl is reacted. 9. The process according to claim ² , wherein an amine in which either R ² or R ³ is hydrogen and the other is methyl is reacted. 10. A compound of the general formula (III): [Wherein A, Z and R ¹ are as defined above]. 11. The phenylglyoxylate according to claim 10, wherein R ¹ is n-butyl. 12. A compound of the general formula (VI): [Wherein X and R ¹ are as defined above].