JP2541783B2 - Methoxyiminoacetonitrile compound and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to a compound of formula [I] which is useful as an agricultural fungicide.

[0002]

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A methoxyiminoacetamide compound represented by the formula [wherein X represents hydrogen, lower alkyl, lower alkoxy or halogen, and ~ means any configuration of E-form, Z-form or a mixture of E-form and Z-form] The present invention relates to a methoxyiminoacetonitrile compound which is an intermediate for the production of and its production method.

[0004]

PRIOR ART AND PROBLEMS The compounds of formula [I] obtained from the intermediates of the present invention are disclosed in Japanese Patent Application No. 2-127441 of the present applicant.
It is a novel compound disclosed for the first time in the publication, which has an excellent bactericidal action against rice blast fungus, rice wilt bacterium, cucumber downy mildew, and the like, and is attracting attention as an agricultural fungicide. In this application, the compound of formula [I] is prepared by several methods, but the present inventors have found that the method for producing the compound of formula [I] is particularly economical and produces less by-products. Furthermore, they have found a novel methoxyiminoacetonitrile compound useful for such a production method and a production method thereof, and completed the present invention.

[0005]

According to the invention, the formula [I]
The compound of formula [II]:

[0006]

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It is produced by reacting a compound represented by the formula [wherein X and ~ are as defined above, W is -CN or -COOR, and R is lower alkyl] with methylamine. In addition, the compound of formula [II] is
II]:

[0008]

[Chemical 6]

Wherein Y is -CN, -COOH or-
COOR, M represents hydrogen or an alkali metal;
R and ~ are as defined above], and a compound of the formula: CH ₃ -L [IV] [wherein L represents halogen or -OSO ₂ OCH ₃ ]. It is produced by subjecting to methylation. Alternatively, the compound of formula [I] is of the formula
[V]:

[0010]

[Chemical 7]

[Wherein, X, M and are as defined above] a compound of the formula: CH ₃ -L [IV] [wherein L represents halogen or -OSO ₂ OCH ₃ ]. It is produced by reacting with a compound represented by In the compound of the formula [II], Z is -CN
A compound of formula [II ′]:

[0012]

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Wherein X and are as defined above.
The compound represented by is a novel compound not described in the literature, and the present invention also provides a compound represented by the formula [II ′]. The compound of the formula [II ′] is a compound in which Y in the above formula [III] is —CN, that is, the compound of the formula [III ′]:

[0014]

[Chemical 9]

It can be obtained by methylating a compound represented by the formula [wherein X, M and are as defined above] with a compound of formula [IV].

The "lower alkyl" represented by X in each compound disclosed in the present specification is an alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, for example, methyl, ethyl,
Propyl, isopropyl, butyl, isobutyl, t-butyl and the like. The "lower alkoxy" is an alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, for example,
Methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like.
Examples of the “halogen” include fluorine, chlorine, bromine, iodine and the like. As the “lower alkyl” for R, the same as for X can be mentioned. Examples of the alkali metal represented by M include potassium and sodium.
As the “halogen” represented by L, the same as those described for X can be mentioned.

According to the production method of the present invention, for example, a lower alcohol such as methanol or ethanol, a solvent such as water, acetone, acetonitrile, benzene, toluene, methylene chloride or chloroform, an organic solvent such as triethylamine or pyridine. In the presence or absence of a base, 1 to 10 mol of methylamine gas is introduced to 1 mol of the compound of the formula [II], or methanol or an aqueous solution of methylamine is used at atmospheric pressure or in a sealed tube. ~ 15
By reacting at 0 ° C. for 15 minutes to 24 hours, the compound of formula [I]
The compound of

The compound of the formula [II] can be obtained by methylating an oxime compound of the formula [III] with a compound of the formula [IV]. For example, this reaction is carried out in the presence of a base such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, sodium hydride, potassium t-butoxide, sodium methylate, sodium ethylate, dimethylformamide, dimethylsulfoxide, -20 to 1 in a solvent such as benzene, toluene, acetone, tetrahydrofuran or a mixed solvent thereof.
The reaction can be carried out at 20 ° C. for 15 minutes to 5 hours. Usually, in the methylation of oxime, a large amount of nitrones may be produced depending on the reaction conditions. However, according to this reaction, by-products are extremely small and the desired compound of the formula [I
I] can be obtained in good yield, especially when Y is -COOH
When the compound of the formula [III] is used, the target compound which can be used in the subsequent reaction can be obtained without purification as in column chromatography. If desired, the compound of formula [II] can be converted to a corresponding compound of another formula [I] by a known method such as conversion of a nitrile to an ester.
It can also be changed to the compound of I].

Alternatively, the compound of formula [I] can be prepared by methylating a compound of formula [V] with a compound of formula [IV]
You can get it directly. This methylation can be performed in the same manner as described above, and the compound of the formula [I] can be obtained in good yield without performing purification such as column chromatography. If desired, the compound of the formula [I] in which X is hydrogen is alkylated or halogenated by a known method,
It is also possible to change the corresponding compound of the formula [I] in which X is lower alkyl or halogen. As described above, the compound of the formula [II ′] is a novel compound, and can be obtained by methylating the compound of the formula [III ′] with the compound of the formula [IV] in the same manner as above. The compounds of formulas [I] to [III] exist in E-form and Z-form or in a mixture thereof. The E-form and Z-form of the compound of the formula [I] can be represented by the following structural formulas.

[0020]

[Chemical 10]

Wherein X and W have the same meanings as described above. ] Expression [VI]:

[0022]

[Chemical 11]

[In the formula, A is --CONHCH ₃ or --C
OOR], that is, W is -CONH
Z-form of CH ₃ or —COOR is a lower alcohol,
By treatment with acid, the formula [VII]:

[0024]

[Chemical 12]

Can be changed to the E-form shown by For example, a compound of formula [VI] in lower alcohol
1 mol of acid such as hydrogen chloride, sulfuric acid or toluene sulfonic acid at 20 to 150 ° C. in air or sealed tube
It can be carried out by reacting for 5 minutes to 48 hours. This reaction can also be carried out on a reaction solution or a crude product in which the compounds of the formulas [VI] and [VII] are present as a mixture. The compounds of the formulas [III] and [III ′] used as starting materials in the method of the present invention include, for example, known 2-phenoxyphenylacetonitrile compounds (US Pat. No. 4,1984,418) and 2-phenoxybenzaldehyde compounds (Japanese Patent Publication No. 58- From No. 50204),
It can be produced by the method described in Reference Example below. In addition, the formula [IV]
The compound is a compound known as a methylating agent. The obtained compound of the formula [I] can be purified, if necessary, by a conventional method, for example, column chromatography, and can be used as an agricultural fungicide by a known method.

[0026]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto. Example 1 Preparation of 2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide (mixture of E-form and Z-form) α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) ) 0.50 g (0.002 mol)
To the mixture, 1 ml of methanol and 3.11 g (0.01 mol) of a 40% aqueous solution of methylamine were added.
The reaction was performed for 8 hours. After the reaction, water was added and extracted with methylene chloride. The extract was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to give 2-methoxyimino-N-methyl-2- (2 -Phenoxyphenyl) acetamide (0.15 g, yield 26.4%) was obtained as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 2.79 (d, 1.75 H, J =
4.9 Hz), 2.87 (d, 1.25 Hz, J = 4.9 Hz), 3.
91 (s, 1.75H), 4.01 (s, 1.25H), 6.32 (b
r, s, 0.58H), 6.64 (br, s, 0.42H), 6.85-
7.61 (m, 9H).

Example 2 Preparation of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 17.12 g (0.06 mol) methyl E-α-methoxyimino-2-phenoxyphenylacetate 60 ml of anhydrous methanol
And 40% methylamine methanol solution 13.98g
(3.0 equivalents) was added and the mixture was heated under reflux for 40 minutes. After the reaction,
The mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane). The obtained crystals were recrystallized from ethyl acetate / n-hexane to give E-
12.21 g (yield 71.6%) of 2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide was obtained as colorless prism crystals (melting point 82-83 ° C). ¹ H NMR (CDCl ₃ ) δ ppm: 2.87 (d, 3H, J = 5.0)
Hz), 3.91 (s, 3H), 6.65 (br, s, 1H), 6.87
~ 7.38 (m, 9H).

Reference Example 1 Production of Methyl E-α-methoxyimino-2-phenoxyphenyl) acetate 0.76 g (0.003 g) of E-α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E form and Z form) Mol) to which 30% hydrochloric acid methanol solution (4.5 ml) was added to obtain 22
The mixture was stirred under reflux for hours. After the reaction, 100 ml of an 8% aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with methylene chloride. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.
The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to give methyl E-α-methoxyimino-2-phenoxyphenyl) acetate 0.40 g (yield 4
6.7%) as colorless crystals (mp 109-110 ° C.). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.48 (m, 9H).

Example 3 Preparation of Methyl E-α-methoxyimino-2-phenoxyphenylacetate E-α-Hydroxyimino-2-phenoxyphenylacetic acid 10.0 ml (0.0389 mol) of dimethyl sulfoxide (50 ml) and toluene (50 ml). To the solution was added sodium methoxide (4.83 g, 0.0894 mol) with stirring under ice cooling, and the mixture was stirred at room temperature for 20 minutes and then cooled. Dimethyl sulfuric acid 11.28 g (0.0894 mol) was added at 6 to 18 ° C over 6 minutes, and the mixture was stirred at room temperature for 4 hours and 30 minutes. After the reaction, 1.2 ml of concentrated hydrochloric acid and 100 ml of water were added to the reaction solution under ice-cooling stirring, and the mixture was extracted with toluene. After washing with water and concentration under reduced pressure, the resulting residue was recrystallized (methanol) and methyl E-α-methoxyimino-2-phenoxyphenylacetate 8.11 g
(Yield 73.1%) was obtained as colorless crystals (melting point 107-109 ° C.). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.46 (m, 9H).

Example 4 Preparation of Methyl E-α-methoxyimino-2-phenoxyphenylacetate 1.29 g (0.005 mol) of E-α-hydroxyimino-2-phenoxyphenylacetic acid was added to 10 ml of dry dimethylformamide and 85%. 0.73 g (0.011 mol) of potassium hydroxide was added, and the mixture was stirred at room temperature for 15 minutes. Dry toluene 1
0 ml, and under ice-cooling, 1.39 g (0.30 g) of dimethyl sulfate.
011 mol) was added dropwise. After stirring for 1.5 hours at room temperature after dropping, 100 ml of ether was added and washing with water was repeated 3 times. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to give methyl E-α-methoxyimino-2-phenoxyphenylacetate.
20 g (84.1% yield) of colorless crystals (mp 109-110)
C). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.46 (m, 9H).

Example 5 E-α-methoxyimino-2- (4-methylphenoxy)
Preparation of methyl phenylacetate 0.87 g (0.32 mol) of E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetic acid was dissolved in 6.4 ml of dry dimethylformamide, and 0.51 g of 85% potassium hydroxide was dissolved. (0.0077 mol), heated and dissolved, and then 6.4 ml of dry toluene was added. Under ice-cooling, 0.97 g (0.0077 mol) of dimethylsulfate / sulfuric acid was added dropwise, and the mixture was stirred at room temperature for 1.5 hours. After the reaction, 50m of water containing 1ml of concentrated hydrochloric acid
l was added and extracted with 50 ml ether. 50 ml of ether layer, then 30% of 4% sodium bicarbonate aqueous solution
Washed in order of ml, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained residue was subjected to silica gel chromatography.
Purification with (ethyl acetate / n-hexane) gave 0.75 g (yield 78.1%) of methyl E-α-methoxyimino-2- (4-methylphenoxy) phenylacetate as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 2.32 (s, 3H), 3.79
(s, 3H), 4.04 (s, 3H), 6.85 to 7.39 (m, 8
H).

Example 6 Preparation of Methyl E-α-methoxyimino-2-phenoxyphenylacetate 1.09 g (0.004 mol) of methyl E-α-hydroxyimino-2-phenoxyphenylacetate was added to 6 ml of dry dimethylformamide and Potassium hydroxide 0.29 g (0.00
(44 mol) was added, and the mixture was stirred at room temperature for 15 minutes. Then, 6 ml of dry toluene was added, and 0.61 g (0.0044 mol) of dimethylsulfate was added dropwise under ice cooling. After dropping, the mixture was stirred at room temperature for 2 hours, then 100 ml of ether was added and washing with water was repeated 3 times. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to give 1.20 g (yield 80.6%) of methyl E-α-methoxyimino-2-phenoxyphenylacetate as colorless crystals (melting point: 1).
09-110 ° C). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.46 (m, 9H). Similarly, the reaction was carried out under the reaction conditions shown in the following table by changing the base and the methylating agent.

[0033]

[Table 1] Example Base Methylating Agent Solvent Reaction Yield (Equivalent) (Equivalent) Condition (%) 7 60% NaH Me ₂ SO ₄ THF 0 ° C. 96.5 (1.1) (1.2) 60 minutes 8 t-BuOK Me ₂ SO ₄ THF 0 ° C. 82.4 (1.3) (1.2) 30 minutes 9 KOH MeI DMF / room temperature 66.6 (1.1) (1.2) PhMe 2 hours t-Bu: t- Butyl, Me: Methyl, THF: Tetrahydrofuran, DMF: Dimethylformamide, PhMe: Toluene

Example 10 E-α-methoxyimino-2- (4-methylphenoxy)
Preparation of methyl phenylacetate 0.71 g (0.0025 mol) of methyl E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetate was dissolved in 10 ml of dry tetrahydrofuran, and 0.13 g (0%) of 60% sodium hydride was dissolved. .0033 mol), stirred at room temperature for 20 minutes, and cooled with ice to 0.44 g (0.000 g of dimethyl sulfate).
(35 mol) in 2.5 ml of dry THF was added dropwise, and the mixture was stirred for 1 hour and 45 minutes under ice cooling. After the reaction, water was added and the pH was adjusted to 1 with concentrated hydrochloric acid. It was extracted twice with methylene chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to methyl E-α-methoxyimino-2- (4-methylphenoxy) phenylacetate.
61 g (yield 81.3%) was obtained as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 2.32 (s, 3H), 3.79
(s, 3H), 4.04 (s, 3H), 6.85 to 7.39 (m, 8
H).

Example 11 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 1.19 g ( To 0.005 mol), 10 ml of dry dimethylformamide and 0.90 g (0.0065 mol) of potassium carbonate were added, and 0.76 g (0.006 mol) of dimethylsulfate was added dropwise under ice cooling, and then 1.
Stir at room temperature for 5 hours. After the reaction, 150 ml of ether was added, and the mixture was washed twice with 100 ml of water. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain α-methoxyimino-2-phenoxyphenylacetonitrile (1.13 g, yield). Rate 89.6%) was obtained as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 4.03 (s, 0.7 H), 4.1
7 (s, 2.3H), 6.89-7.67 (m, 9H).

Example 12 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 1.19 g ( (0.005 mol), dry dimethylformamide (10 ml) and potassium carbonate (0.90 g, 0.006 mol) were added, and methyl iodide (0.78 g, 0.0055 mol) was added dropwise under ice cooling, and the mixture was allowed to stand at room temperature for 4 hours. And stirred. After the reaction, 150 ml of ether was added, and the mixture was washed twice with 100 ml of water. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 1.06 g (yield: 84.0%) of α-methoxyimino-2-phenoxyphenylacetonitrile as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 4.03 (s, 0.7 H), 4.1
7 (s, 2.3H), 6.89-7.69 (m, 9H).

Example 13 Preparation of α-methoxyimino-2- (4-chlorophenoxy) phenylacetonitrile (mixture of E-form and Z-form) α-hydroxyimino-2- (4-chlorophenoxy) phenylacetonitrile (E-form) And Z-body mixture) 1.36 g
(0.005 mol) was dissolved in 10 ml of dry dimethylformamide, 0.90 g (0.0065 mol) of potassium carbonate was added, and 0.76 g (0.006 mol) of dimethyl sulfate was added under ice-cooling.
Was added and stirred at room temperature for 1 hour. 150 ml of ether was added and washed twice with water. The ether layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain α-methoxyimino-2- (4-chlorophenoxy).
1.35 g (94.4% yield) of phenylacetonitrile was obtained as a pale yellow oil. ¹ H NMR (CDCl ₃ ) δ ppm: 4.02 (s, 0.69 H), 4.
17 (s, 2.31H), 6.90-7.68 (m, 8H).

Example 14 Preparation of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide E-2-Hydroxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 10. 00g (0.037
Mol) in acetone 200 ml, potassium carbonate 15.34 g
(0.111 mol) and 9.33 g (0.07 g) of dimethylsulfate.
4 mol) and stirred at room temperature for 9 hours. After the reaction, it was filtered, washed with acetone, and concentrated under reduced pressure. The obtained oily substance was dissolved in 50 ml of toluene, 50 ml of a 1N sodium hydroxide aqueous solution was added, and the mixture was stirred at room temperature for 30 minutes. Extract with toluene, wash with water, concentrate under reduced pressure, recrystallize the obtained residue
(Methanol / water) followed by E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 9.
93 g (yield 94.4%) of colorless crystals (mp 81.5-83)
C). ¹ H NMR (CDCl ₃ ) δ ppm: 2.87 (d, 3H, J = 5.0)
Hz), 3.91 (s, 3H), 6.65 (br.s, 1H), 6.87
~ 7.38 (m, 9H).

Example 15 E-2-Methoxyimino-N-methyl-2- [2- (4-
Preparation of methylphenoxy) phenyl] acetamide E-2-hydroxyimino-N-methyl-2- [2- (4
1.00 g of -methylphenoxy) phenyl] acetamide
(0.0035 mol) was dissolved in 7 ml of dry acetone, and 0.63 g (0.0046 mol) of potassium carbonate and 0.36 g of dimethyl sulfate were dissolved.
53 g (0.0042 mol) was added and reacted at room temperature for 22 hours. After the reaction, water was added, the mixture was extracted twice with methylene chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to give E-2-methoxyimino-N.
-Methyl-2- [2- (4-methylphenoxy) phenyl]
0.96 g (yield 92.3%) of colorless crystals of acetamide were obtained. ¹ HNMR (CDCl ₃ ) δppm: 2.29 (s, 3H), 2.81
(d, 3H, J = 4.9 Hz), 3.89 (s, 3H), 6.71 (b
rs, 1H), 6.82 (d, 1H, J = 8.1 Hz), 6.89-
6.92 (m, 2H), 7.05 to 7.10 (m, 3H), 7.23
~ 7.31 (m, 2H).

Reference Example 2 Production of E-2-hydroxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 39.60 g of crude methyl E-α-hydroxyimino-2-phenoxyphenylacetate (purity 51.2) %, 0.0747
To 100 mol of methanol and 15.45 g (0.199 mol) of a 40% aqueous solution of methylamine.
Stirred for hours. Then, a 40% aqueous methylamine solution 7.
73 g (0.0995 mol) was added, and the mixture was stirred in an oil bath at 70 ° C. for 6 hours. After the reaction, 200 ml of water and 100 ml of toluene
ml was added, and the mixture was stirred with ice cooling for 1 hour. The precipitated crystals were collected by filtration and recrystallized (methanol / toluene) to give 12.31 g (yield 60.1%) of E-2-hydroxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide as colorless crystals. (Melting point 18
3-184.5 ° C.). ¹ H NMR (d ₆ -DMSO) δ ppm: 2.65 (d, 3H, J =
4.5 Hz), 6.30 to 7.47 (m, 9H), 7.92 (m, 1
H, J = 4.5 Hz).

Reference Example 3 E-2-Hydroxyimino-N-methyl-2- [2- (4
Preparation of -Methylphenoxy) phenyl] acetamide 1.00 g (0.0035 mol) of methyl E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetate was dissolved in 7 ml of methanol to prepare a 40% methylamine methanol solution 0 0.54 g (0.007 mol) was added and refluxed for 70 minutes. Further, 1.3% of a 40% methylamine methanol solution was used.
6 g (0.0175 mol) were added and refluxed for 3 hours. After the reaction, the mixture was concentrated under reduced pressure to obtain 1.00 g (yield: 100.0%) of E-2-hydroxyimino-N-methyl-2- [2- (4-methylphenoxy) phenyl] acetamide as amorphous. ¹ H NMR (CDCl ₃ ) δ ppm: 2.31 (s, 3H), 2.86
(d, 3H, J = 5.9 Hz) 6.60 (br.s, 1H), 6.84-
7.36 (m, 8H), 7.93 (br.s, 1H).

Reference Example 4 Production of E-α-hydroxyimino-2-phenoxyphenylacetic acid 9.99 g (0.0368 mol) of methyl E-α-hydroxyimino-2-phenoxyphenylacetate was mixed with 3 parts of methanol.
6.8 ml, 3.23 g (0.081 mol) of sodium hydroxide and 36.8 ml of water were added, and the mixture was heated under reflux for 1 hour. After heating, 11 ml of concentrated hydrochloric acid was added under ice cooling, and the precipitated crystals were collected by filtration and recrystallized (methanol / ethyl acetate / n-hexane) to give 6.90 g of α-hydroxyimino-2-phenoxyphenylacetic acid (yield). Rate 72.9%) was obtained as colorless crystals (decomposition 180 ° C). ¹ H NMR (d ₆ -DMSO) δ ppm: 6.83 to 7.38 (m, 9
H), 12.26 (br.s, 1H), 12.85 (br.s, 1H).

Reference Example 5 Production of E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetic acid Methyl E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetate 1.00 g (0.0035) (Mole) methanol 3.5 ml, water 3.5 ml, sodium hydroxide 0.3
1 g (0.0077 mol) was added, and the mixture was heated under reflux for 1 hour. After cooling to room temperature, the pH was adjusted to 1 with a 5% aqueous solution of hydrochloric acid, the mixture was stirred at room temperature, the crystals were collected by filtration, washed with water and colorless crystals of α-hydroxyimino-2- (4-methylphenoxy) phenylacetic acid. 90 g (yield 94.7%) was obtained. ¹ H NMR (d ₆ -DMSO) δ ppm: 2.27 (s, 3H), 6.
78-7.37 (m, 8H).

Reference Example 6 Preparation of α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 0.55 g (0.02 g) of sodium was added to 15 ml of anhydrous ethanol.
4 mol) was dissolved, and a mixture of 4.18 g (0.02 mol) of 2-phenoxyphenylacetonitrile and 3 ml of absolute ethanol was added dropwise at 0 ° C. over 7 minutes. Further, 3.51 g (0.03 mol) of isoamyl nitrite was added at 0 ° C. or lower to 1
The mixture was added dropwise for 0 minutes and stirred at room temperature for 24 hours. After the reaction,
100 ml of a 5% hydrochloric acid aqueous solution was added, extracted with ether, and dried over anhydrous magnesium sulfate. The crude product obtained by concentration under reduced pressure was subjected to silica gel chromatography (ethyl acetate / n
-Hexane) to give α-hydroxyimino-2-
4.53 g of phenoxyphenylacetonitrile (yield 95.
1%) as low melting crystals. ¹ H NMR (CDCl ₃ ) δ ppm: 6.83 to 7.67 (m, 9
H), 8.68 (br.s, 0.25H), 9.02 (br.s, 0.75H)
H).

Reference Example 7 Preparation of α-hydroxyimino-2- (4-chlorophenoxy) phenylacetonitrile (mixture of E form and Z form) 0.57 g (0.0) of sodium metal in 25 ml of anhydrous ethanol.
After melting, 8.53 g (0.03 g) of 2- (4-chlorophenoxy) phenylacetonitrile was added under ice-cooling.
(5 mol) was added dropwise to a solution of 7 ml of absolute ethanol. Then, 6.15 g (0.0525 mol) of isoamyl nitrite was added dropwise, and the mixture was reacted for 2.5 hours at room temperature. Water was added, the pH was adjusted to 1 with concentrated hydrochloric acid, extracted with ether, washed with water, and dried over anhydrous water. Dried over magnesium sulfate. The ether was concentrated under reduced pressure,
The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane), and 9.03 g (yield 94.6%) of α-hydroxyimino-2- (4-chlorophenoxy) phenylacetonitrile was pale brown. Obtained as a viscous liquid. ¹ H NMR (CDCl ₃ ) δ ppm: 6.90 to 7.68 (m, 8
H), 9.12 (br.s, 0.28H), 9.46 (br.s, 0.72)
H).

Reference Example 8 Production of E-α-hydroxyimino-2-phenoxyphenylacetic acid α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E form and Z form) 0.71 g (0.003 mol) 3 ml of ethanol, 0.40 g of potassium hydroxide (0.
0072 mol) and 3 ml of water, and the mixture was refluxed for 24 hours. After the reaction, 10 ml of methylene chloride and 10% aqueous hydrochloric acid were added, and the precipitated crystals of α-hydroxyimino-2-phenoxyphenylacetic acid were collected by filtration to obtain 0.47 g (yield: 60.9%) of colorless crystals. ¹ H NMR (d ₆ -DMSO) δ ppm: 6.83 to 7.38 (m, 9
H), 12.26 (br.s, 1H), 12.85 (br.s, 1H).

Reference Example 9 Preparation of 2-phenoxybenzaldoxime To 49.96 g (0.025 mol) of 2-phenoxybenzaldehyde, 50 ml of anhydrous methanol and 2.08 g (0.03 mol) of hydroxylamine hydrochloride were added at 60 ° C. It was stirred for 3 hours. After the reaction, 200 ml of water was added, extracted with methylene chloride, and dried over magnesium sulfate. The crude product obtained by concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 3.95 g (yield: 74.1%) of 2-phenoxybenzaldoxime as a colorless oil. ¹ H NMR (CDCl ₃ ) δ ppm: 6.88 to 7.41 (m, 8)
H), 7.45 (s, 1H), 7.86 (dd, 1H, J = 7.9,
2.0) 8.49 (s, 1H).

Example 16 Preparation of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 2-phenoxybenzaldoxime 1.07 g (0.00
(5 mol), 10 ml of dry ether was added, 0.46 g (0.0065 mol) of chlorine was introduced at -10 ° C or lower, and then 0 ° C.
The mixture was stirred for 5 hours. After the reaction, the reaction solution was concentrated under reduced pressure, and 10 ml of dry methylene chloride and 0.86 g (0.0055 mol) of tetraethylammonium cyanide were added to the obtained residue.
Was added and the mixture was stirred overnight at room temperature. After the reaction, add 150 ml of water, extract with methylene chloride, dry over anhydrous magnesium sulfate, and chromatograph on silica gel (ethyl acetate / n
-Hexane) to obtain a crude product of α-hydroxyimino-2-phenoxyphenylacetonitrile.
To 51 g was added 4 ml of dry dimethylformamide and 0.36 g (0.0026 ml) of potassium carbonate. Further, 0.30 g (0.0024 mol) of dimethyl sulfate was added under ice cooling, and the mixture was stirred at room temperature for 2 hours. After the reaction, 100 ml of ether was added, washed twice with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 0.21 g (yield 16.6%) of α-methoxyimino-2-phenoxyphenylacetonitrile as an anhydrous oil. ¹ H NMR (CDCl ₃ ) δ ppm: 4.03 (s, 0.7 H), 4.1
7 (s, 2.3H), 6.89-7.67 (m, 9H).

Example 17 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 500 ml of n-butyllithium (1.62 mol hexane solution)
(0.81 mol), diphenyl ether 20 at 5 ℃ or less
A mixture of 6.81 g (1.215 mol) and 405 ml of dry tetrahydrofuran was added dropwise over 40 minutes and stirred at room temperature for 24 hours. After the reaction, to a stirred solution of dimethyl oxalate (118.09 g, 1.215 mol) dissolved in dry tetrahydrofuran (810 ml) was added dropwise at 50 ° C or lower over 50 minutes, and the mixture was stirred at room temperature for 24 hours. After the reaction, ice water 2
l was added and the mixture was extracted with 500 ml of toluene, and the extract was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 302.94 g of a brown oily substance. To this oil are added 1.3 l of methanol and 47.25 g of hydroxylamine hydrochloride (0.25 g).
68 mol), and heated under reflux for 1 hour.
A solution prepared by dissolving 79.2 g (1.98 mol) of sodium hydroxide in 0 ml was added and the mixture was refluxed for 1 hour. After the reaction, methanol was distilled off under reduced pressure, 1.8 l of water was added, and 1 l of methylene chloride was added.
And concentrated hydrochloric acid was added to the aqueous layer until the pH became 2 or less. The precipitated crystals were collected by filtration, and 141.55 g of crude crystals of E-α-hydroxyimino-2-phenoxyphenylacetic acid were collected.
(From a yield of 68.0% n-butyllithium). To 25.73 g (0.1 mol) of the obtained crude crystals, 150 ml of dry dimethylformamide and 14.4% of 85% potassium hydroxide were added.
52 g (0.22 mol) was added and dissolved while heating, 150 ml of dry toluene was added, and 27.75 g (0.22 mol) of dimethyl sulfate was added dropwise at 25-30 ° C over 5 minutes, and then at room temperature for 1.5 hours. Stirred. After the reaction, 700 ml of 1% hydrochloric acid aqueous solution
Was extracted with 500 ml of toluene, and the extract was washed with a 2% aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The crude product obtained by concentration under reduced pressure was recrystallized (methanol) and purified, and 21.15 g of methyl E-α-methoxyimino-2-phenoxyphenylacetate was obtained (yield 74.1).
%) As colorless crystals (melting point 109-110 ° C). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.46 (m, 9H).

Example 18 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate Methyl Z-α-methoxyimino-2-phenoxyphenylacetate VI '0.29 g (1.0 mmol) and dry methanol 3
ml and 10% hydrochloric acid methanol solution 0.36 g (1.0 mmol) were added, and the mixture was heated under reflux for 6 hours for isomerization. After the reaction, 0.29 g of the residue obtained by evaporation under reduced pressure was a pure mixture of E isomer and Z isomer, and the production ratio was 77.6: 22.4.
(NMR quantification).

Example 19 Preparation of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide Z-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide VI " 0.28g (1.0mmo
To l), 3 ml of dry methanol and 0.36 g (1.0 mmol) of a 10% methanol solution of hydrochloric acid were added, and the mixture was heated under reflux for 6 hours for isomerization. After the reaction, the residue obtained by evaporation under reduced pressure was 0.2
8 g was a pure mixture of E isomer and Z isomer, and the production ratio was 91.5: 8.5 (NMR quantitative determination).

[0052]

INDUSTRIAL APPLICABILITY According to the present invention, a novel methoxyiminoacetonitrile compound useful as an intermediate for the economical production of a methoxyiminoacetamide compound useful as an agricultural fungicide and having a small amount of by-product formation, and a method for producing the same. Will be provided.

Front Page Continuation (72) Inventor Masahiko Nagai 4-4-8-608 Kise Minamishinmachi, Amagasaki City, Hyogo Prefecture (56) Reference JP-A-55-35006 (JP, A)

Claims (2)

(57) [Claims] 1. The formula [II ′]: [Wherein, X means hydrogen, lower alkyl, lower alkoxy or halogen, and ~ means any configuration of E form, Z form or mixture of E form and Z form]. 2. The formula [III ′]: [Wherein, X represents hydrogen, lower alkyl, lower alkoxy or halogen, M represents hydrogen or an alkali metal, and represents an E-form, a Z-form or a mixture of E- and Z-forms] A compound represented by the formula: CH ₃ -L [IV], wherein L represents halogen or —OSO ₂ OCH _3.
[II ']: [Wherein X and-have the same meanings as defined above].