JP2583024B2 - Method for producing methoxyiminoacetamide compound - Google Patents

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【０００１】[0001]

【産業上の利用分野】本発明は、農業用殺菌剤として有
用な、式[Ｉ]:The present invention relates to a compound of formula [I] which is useful as an agricultural fungicide.

【０００２】[0002]

【化３】 Embedded image

【０００３】[式中、Ｘは水素、低級アルキル、低級ア
ルコキシまたはハロゲン、〜はＥ体、Ｚ体またはＥ体と
Ｚ体の混合物のいずれかの配置を意味する]で示される
メトキシイミノアセトアミド化合物の製造法に関する。A methoxyiminoacetamide compound represented by the formula: wherein X represents hydrogen, lower alkyl, lower alkoxy or halogen, and-represents an E-form, a Z-form or a mixture of E-form and Z-form. A method for producing the same.

【０００４】[0004]

【従来の技術および課題】本発明の式[Ｉ]の化合物は、
本出願人の特願平２−１２７４４１号において初めて開
示された新規化合物で、イネいもち病菌、イネ紋枯病
菌、キュウリべと病菌等に対して優れた殺菌作用を有
し、農業用殺菌剤として注目されている化合物である。
該出願においては、式[Ｉ]の化合物は幾つかの方法によ
り製造されているが、本発明者らは、特に、経済的な、
副生物の生成の少ない式[Ｉ]の化合物の製造法を見いだ
し、本発明を完成するに至った。BACKGROUND OF THE INVENTION The compounds of the formula [I] according to the invention are:
A novel compound disclosed for the first time in Japanese Patent Application No. 2-127441 of the present applicant, which has an excellent bactericidal action against rice blast, rice sheath blight, cucumber downy mildew, etc., and is a fungicide for agricultural use. It is a compound that has attracted attention.
In this application, the compounds of formula [I] have been prepared by several methods, but the inventors have found, inter alia, economical,
The present inventors have found a method for producing a compound of the formula [I] with less generation of by-products, and have completed the present invention.

【０００５】[0005]

【課題を解決するための手段】式[Ｉ]の化合物は、式
［ＩＩ］：The compound of the formula [I] has the formula [II]:

【０００６】[0006]

【化４】 Embedded image

【０００７】［式中、Ｘおよび〜は前記と同意義、Ｗは
−ＣＮまたは−ＣＯＯＲ、Ｒは低級アルキルを意味す
る］で示される化合物のメチルアミンを反応させること
により製造できる。また、式［ＩＩ］の化合物は、式
「ＩＩＩ］：Wherein X and are the same as defined above, W is -CN or -COOR, and R is lower alkyl. Also, the compound of formula [II] has the formula “III]:

【０００８】[0008]

【化５】 Embedded image

【０００９】［式中、Ｙは−ＣＮ、−ＣＯＯＨまたは−
ＣＯＯＲ、Ｍは水素またはアルカリ金属を意味し、Ｘ、
Ｒおよび〜は前記と同意義である］で示される化合物
を、式： ＣＨ₃−Ｌ ［ＩＶ］ ［式中、Ｌはハロゲンまたは−ＯＳＯ₂ＯＣＨ₃を意味す
る］で示される化合物と反応させてメチル化させること
により製造できる。本発明においては、式［Ｉ］の化合
物は、式[Ｖ］：Wherein Y is -CN, -COOH or-
COOR, M represents hydrogen or an alkali metal;
Wherein R and are as defined above, are reacted with a compound represented by the formula: CH ₃ -L [IV] wherein L represents halogen or —OSO ₂ OCH _3. And methylation. In the present invention, the compound of the formula [I] is represented by the formula [V]:

【００１０】[0010]

【化６】 Embedded image

【００１１】［式中、Ｘ、Ｍおよび〜は前記と同意義で
ある]で示される化合物を、式: ＣＨ₃−Ｌ [ＩＶ] [式中、Ｌはハロゲンまたは−ＯＳＯ₂ＯＣＨ₃を意味す
る]で示される化合物と反応させてメチル化することに
より製造される。式[ＩＩ]の化合物のうちＺが−ＣＮの
化合物、すなわち、式[ＩＩ']:A compound represented by the formula: wherein X, M and are as defined above, are represented by the formula: CH ₃ -L [IV] wherein L is halogen or —OSO ₂ OCH ₃ And methylation. Among the compounds of the formula [II], compounds wherein Z is -CN, that is, a compound of the formula [II ']:

【００１２】[0012]

【化７】 Embedded image

【００１３】[式中、Ｘおよび〜は前記と同意義である]
で示される化合物は文献未記載の新規化合物である。式
[ＩＩ']の化合物は、前記の式[ＩＩＩ]におけるＹが−
ＣＮの化合物、すなわち、式[ＩＩＩ’］：Wherein X and are as defined above.
Is a novel compound not described in any literature. formula
The compound of the formula [II ′] is represented by the formula [III] wherein Y is-
A compound of CN, ie, formula [III ']:

【００１４】[0014]

【化８】 Embedded image

【００１５】［式中、Ｘ、Ｍおよび〜は前記と同意義で
ある]で示される化合物を、式[ＩＶ]の化合物でメチル
化することにより得られる。Wherein X, M and are as defined above, are methylated with a compound of formula [IV].

【００１６】本明細書に開示する各化合物におけるＸで
示される「低級アルキル」としては、炭素数１〜６、好ま
しくは、１〜４のアルキル、例えば、メチル、エチル、
プロピル、イソプロピル、ブチル、イソブチル、t−ブ
チル等が挙げられる。「低級アルコキシ」としては、炭素
数１〜６、好ましくは、１〜４のアルコキシ、例えば、
メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブ
トキシ、イソブトキシ、t−ブトキシ等が挙げられる。
「ハロゲン」としては、フッ素、塩素、臭素、ヨウ素等が
挙げられる。Ｒで示される「低級アルキル」としてはＸに
おける同様なものが挙げられる。Ｍで示されるアルカリ
金属としては、カリウム、ナトリウム等が挙げられる。
Ｌで示される「ハロゲン」としては、Ｘにおける同様なも
のが挙げられる。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. As the "lower alkoxy", 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.
"Halogen" includes fluorine, chlorine, bromine, iodine and the like. As the “lower alkyl” represented by R, the same as those described 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.

【００１７】例えば、メタノール、エタノールのような
低級アルコール、水、アセトン、アセトニトリル、ベン
ゼン、トルエン、塩化メチレンおよびクロロホルムのよ
うな溶媒中、トリエチルアミン、ピリジンのような有機
塩基の存在下または不存在下、式[ＩＩ]の化合物１モル
に対して１〜１０モルのメチルアミンガスを導入するか
メチルアミンのメタノールまたは水溶液を用いて大気圧
下または封管中、０〜１５０℃にて１５分〜２４時間反
応させることにより式[Ｉ]の化合物が得られる。For example, in a solvent such as lower alcohol such as methanol and ethanol, water, acetone, acetonitrile, benzene, toluene, methylene chloride and chloroform, in the presence or absence of an organic base such as triethylamine and pyridine, 1 to 10 mol of methylamine gas is introduced into 1 mol of the compound of the formula [II], or using methanol or aqueous solution of methylamine under atmospheric pressure or in a sealed tube at 0 to 150 ° C. for 15 minutes to 24 hours. Reaction for a time gives the compound of formula [I].

【００１８】式[ＩＩ]の化合物は、式[ＩＩＩ]のオキシ
ム化合物を式[ＩＶ]の化合物でメチル化することにより
得ることができる。例えば、この反応は、炭酸カリウ
ム、炭酸ナトリウム、水酸化カリウム、水酸化ナトリウ
ム、水素化ナトリウム、t−ブトキシカリウム、ナトリ
ウムメチラート、ナトリウムエチラートのような塩基の
存在下、ジメチルホルムアミド、ジメチルスルホキシ
ド、ベンゼン、トルエン、アセトン、テトラヒドロフラ
ンまたはこれらの混合溶媒のような溶媒中、−２０〜１
２０℃にて、１５分〜５時間反応させることにより行え
る。通常、オキシムのメチル化に際しては、反応条件に
よってニトロン体が多量に生成する場合があるが、この
反応によれば副生物が非常に少なく、目的とする式[Ｉ
Ｉ]の化合物が収率よく得られ、特に、Ｙが−ＣＯＯＨ
の式[ＩＩＩ]の化合物を用いる場合は、カラムクロマト
グラフィーによるような精製なしに、以後の反応に用い
ることができる目的化合物が得られる。なお、所望によ
り、例えば、ニトリルのエステルへの変換のような公知
の方法により、式[ＩＩ]の化合物を対応する他の式[Ｉ
Ｉ]の化合物へ変えることもできる。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].

【００１９】本発明の製造法によれば、式[Ｉ]の化合物
は、式[Ｖ]の化合物を式[ＩＶ]の化合物でメチル化する
ことにより、直接得ることができる。このメチル化も前
記と同様にして行うことができ、カラムクロマトグラフ
ィーのような精製を行うことなく式[Ｉ]の化合物を収率
よく得ることができる。所望により、Ｘが水素の得られ
た式[Ｉ]の化合物を公知の方法によりアルキル化やハロ
ゲン化して、Ｘが低級アルキルやハロゲンの対応する式
[Ｉ]の化合物に変えることもできる。前記のごとく、式
[ＩＩ']の化合物は新規化合物であり、式[ＩＩＩ']の化
合物を前記と同様に、式[ＩＶ]の化合物でメチル化する
ことにより得られる。式[Ｉ]〜[ＩＩＩ]および［Ｖ］の
化合物はＥ体およびＺ体またはその混合物として存在す
る。式[ＩＩ]の化合物についてＥ体およびＺ体はつぎの
構造式で示すことができる。According to the process of the present invention, the compound of the formula [I] can be obtained directly by methylating the compound of the formula [V] with the compound of the formula [IV]. 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 formula [I] in which X is hydrogen is alkylated or halogenated by a known method, and X is a corresponding compound of lower alkyl or halogen.
It can also be changed to the compound of [I]. As mentioned above, the equation
The compound of [II '] is a novel compound and is obtained by methylating the compound of formula [III'] with the compound of formula [IV] in the same manner as described above. The compounds of the formulas [I] to [III] and [V] exist as E-form and Z-form or a mixture thereof. The E-form and the Z-form of the compound of the formula [II] can be represented by the following structural formulas.

【００２０】[0020]

【化９】 Embedded image

【００２１】[式中、ＸおよびＷは前記と同意義を有す
る。]式[ＶＩ]:Wherein X and W have the same meanings as described above. ] Formula [VI]:

【００２２】[0022]

【化１０】 Embedded image

【００２３】[式中、Ａは−ＣＯＮＨＣＨ₃または−ＣＯ
ＯＲ]で示されるＺ体の化合物は、低級アルコール中、
酸で処理することにより、式[ＶＩＩ］：Wherein A is —CONHCH ₃ or —CO
OR], a Z-form compound represented by the formula:
By treatment with an acid, the compound of formula [VII]:

【００２４】[0024]

【化１１】 Embedded image

【００２５】で示されるＥ体に変えることができる。例
えば、式［ＶＩ]の化合物を低級アルコール中、０.１〜
１０モルの塩化水素、塩酸、硫酸またはトルエンスルホ
ン酸のような酸と大気中または封管中で２０〜１５０℃
にて１５分〜４８時間反応させることにより行うことが
できる。また、この反応は式[ＶＩ]と式[ＶＩＩ]の化合
物が混合して存在している反応溶液および粗製物に対し
ても実施することができる。式[ＩＩＩ]および[ＩＩ
Ｉ']の化合物は、例えば、公知の２−フェノキシフェニ
ルアセトニトリル化合物(米国特許第４１９８４１８号)
や２−フェノキシベンズアルデヒド化合物(特公昭５８
−５０２０４号)から、後記参考例に記載の方法で製造
できる。また、式[ＩＶ]の化合物はメチル化剤として公
知の化合物である。得られた式[Ｉ]の化合物は、要すれ
ば、常法、例えば、カラムクロマトグラフィーにより精
製することができ、公知の方法により農業用殺菌剤とし
て使用することができる。Can be changed to the E-form shown by For example, a compound of the formula [VI] may be prepared in a lower alcohol at 0.1 to 0.1
20-150 ° C. in air or in a sealed tube with an acid such as 10 mol of hydrogen chloride, hydrochloric acid, sulfuric acid or toluenesulfonic acid.
For 15 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. Formulas [III] and [II
The compound of I ′] is, for example, a known 2-phenoxyphenylacetonitrile compound (US Pat. No. 4,198,418).
And 2-phenoxybenzaldehyde compounds (JP-B-58)
-50204) by the method described in Reference Examples below. The compound of the formula [IV] 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】[0026]

【実施例】つぎに、参考例および実施例を挙げて本発明
をさらに詳細に説明するが、本発明はこれらに限定され
るものではない。 参考例１ ２−メトキシイミノ−Ｎ−メチル−２−(２−フェノキ
シフェニル)アセトアミド(Ｅ体とＺ体の混合物)の製造 α−メトキシイミノ−２−フェノキシフェニルアセトニ
トリル(Ｅ体とＺ体の混合物)０.５０g(０.００２モル)
に、メタノール１mlおよび４０％メチルアミン水溶液
３.１１g(０.０１モル)を加え、封管中１００℃にて１
８時間反応した。反応後、水を加えて塩化メチレンで抽
出した。抽出液を無水硫酸マグネシウムで乾燥し、減圧
下で濃縮し、得られた残渣をシリカゲルクロマトグラフ
ィー(酢酸エチル／n−ヘキサン)で精製を行い、２−メ
トキシイミノ−Ｎ−メチル−２−(２−フェノキシフェ
ニル)アセトアミド０.１５g(収率２６.４％)を無色油状
物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.７９(d,１.７５Ｈ,Ｊ＝
４.９Ｈz)、２.８７(d,１.２５Ｈ,Ｊ＝４.９Ｈz)、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)。EXAMPLES Next, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is not limited thereto. Reference Example 1 Production 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).

【００２７】参考例２ Ｅ−２−メトキシイミノ−Ｎ−メチル−２−(２−フェ
ノキシフェニル)アセトアミドの製造 Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチル１７.１２g(０.０６モル)に、無水メタノール６
０mlおよび４０％メチルアミンメタノール溶液１３.９
８g(３.０当量)を加えて４０分間加熱還流した。反応
後、減圧下で濃縮し、得られた残渣をシリカゲルクロマ
トグラフィー(酢酸エチル／n−ヘキサン)で精製した。
得られた結晶を酢酸エチル／n−ヘキサンで再結晶し、
Ｅ−２−メトキシイミノ−Ｎ−メチル−２−(２−フェ
ノキシフェニル)アセトアミド１２.２１g(収率７１.６
％)を無色プリズム晶(融点８２〜８３℃)として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm: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 2 Preparation of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 17.12 g (0.06 mol) of methyl E-α-methoxyimino-2-phenoxyphenylacetate And anhydrous methanol 6
0 ml and 13.9% methanol solution of methylamine 13.9
8 g (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,
12.21 g of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide (71.6 yield)
%) As colorless prisms (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).

【００２８】参考例３ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 Ｅ−α−メトキシイミノ−２−フェノキシフェニルアセ
トニトリル(Ｅ体とＺ体の混合物)０.７６g(０.００３モ
ル)に、３０％塩酸メタノール溶液４.５mlを加えて２２
時間還流撹拌した。反応後、８％炭酸水素ナトリウム水
溶液１００mlを加え、塩化メチレンで抽出した。抽出液
を無水硫酸マグネシウムで乾燥し、減圧下で濃縮した。
得られた残渣をシリカゲルクロマトグラフィー(酢酸エ
チル／n−ヘキサン)で精製し、Ｅ−α−メトキシイミノ
−２−フェノキシフェニル酢酸メチル０.４０g(収率４
６.７％)を無色結晶(融点１０９〜１１０℃)として得
た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:３.７８(s,３Ｈ)、４.０３
(s,３Ｈ)、６.８６〜７.４８(m,９Ｈ)。Reference Example 3 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 0.76 g (0.003 mol) of E-α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) ) Was added with 4.5 ml of a 30% methanol solution of hydrochloric acid to give 22
The mixture was stirred under reflux for an hour. 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 resulting residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 0.40 g of methyl E-α-methoxyimino-2-phenoxyphenylacetate (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).

【００２９】参考例４ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸１０.００g(０.０３８９モル)のジメチルスルホキシ
ド５０mlおよびトルエン５０mlの溶液に氷冷撹拌下、ナ
トリウムメトキシド４.８３g(０.０８９４モル)を加
え、室温で２０分間撹拌した後冷却した。ジメチル硫酸
１１.２８g(０.０８９４モル)を６〜１８℃にて６分間
で加え、室温で４時間３０分撹拌した。反応後、濃塩酸
１.２mlおよび水１００mlを氷冷撹拌下、反応液に加
え、トルエンで抽出した。水洗後、減圧濃縮し、得られ
た残渣を再結晶(メタノール)してＥ−α−メトキシイミ
ノ−２−フェノキシフェニル酢酸メチル８.１１g(収率
７３.１％)を無色結晶(融点１０７〜１０９℃)として得
た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:３.７８(s,３Ｈ)、４.０３
(s,３Ｈ)、６.８６〜７.４６(m,９Ｈ)。Reference Example 4 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 10.00 g (0.0389 mol) of E-α-hydroxyimino-2-phenoxyphenylacetic acid 50 ml of dimethylsulfoxide and 50 ml of toluene Under ice-cooling and stirring, the solution was added with sodium methoxide (4.83 g, 0.0894 mol), stirred at room temperature for 20 minutes and cooled. Dimethyl sulfate (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 and stirring, and extracted with toluene. After washing with water, the mixture was concentrated under reduced pressure, and the obtained residue was recrystallized (methanol) to give 8.11 g (yield: 73.1%) of methyl E-α-methoxyimino-2-phenoxyphenylacetate as colorless crystals (melting point: 107 to 10%). 109 ° C). ¹ H NMR (CDCl ₃ ) δ ppm: 3.78 (s, 3H), 4.03
(s, 3H), 6.86-7.46 (m, 9H).

【００３０】参考例５ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸１.２９g(０.００５モル)に乾燥ジメチルホルムアミ
ド１０mlと８５％水酸化カリウム０.７３g(０.０１１モ
ル)を加え、室温下１５分間撹拌した。乾燥トルエン１
０mlを加え、さらに氷冷下でジメチル硫酸１.３９g(０.
０１１モル)を滴下した。滴下後１.５時間、室温で撹拌
した後、エーテル１００mlを加えて水洗を３回繰り返し
た。エーテル層を無水硫酸マグネシウムで乾燥し、減圧
濃縮した。得られた残渣をシリカゲルクロマトグラフィ
ー(酢酸エチル／n−ヘキサン)にて精製してＥ−α−メ
トキシイミノ−２−フェノキシフェニル酢酸メチル１.
２０g(収率８４.１％)を無色結晶(融点１０９〜１１０
℃)として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:３.７８(s,３Ｈ)、４.０３
(s,３Ｈ)、６.８６〜７.４６(m,９Ｈ)。Reference Example 5 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 1.29 g (0.005 mol) of E-α-hydroxyimino-2-phenoxyphenylacetic acid was mixed with 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 three 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).

【００３１】参考例６ Ｅ−α−メトキシイミノ−２−(４−メチルフェノキシ)
フェニル酢酸メチルの製造 Ｅ−α−ヒドロキシイミノ−２−(４−メチルフェノキ
シ)フェニル酢酸０.８７g(０.３２モル)を乾燥ジメチル
ホルムアミド６.４mlに溶解し、８５％水酸化カリウム
０.５１g(０.００７７モル)を添加し、加温、溶解した
後、乾燥トルエン６.４mlを加えた。氷冷下、ジメチル
硫酸０.９７g(０.００７７モル)を滴下し、室温で１.５
時間撹拌した。反応後、濃塩酸１mlを含む水５０mlを添
加し、５０mlのエーテルで抽出した。エーテル層を水５
０ml、ついで、４％重炭酸ナトリウム水溶液３０mlの順
に洗浄し、無水硫酸ナトリウムで乾燥し、減圧濃縮し、
得られた残渣をシリカゲルクロマトグラフィー(酢酸エ
チル／n−ヘキサン)にて精製してＥ−α−メトキシイミ
ノ−２−(４−メチルフェノキシ)フェニル酢酸メチル
０.７５g(収率７８.１％)を無色油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.３２(s,３Ｈ)、３.７９
(s,３Ｈ)、４.０４(s,３Ｈ)、６.８５〜７.３９(m,８
Ｈ)。Reference Example 6 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 dimethyl sulfate was added dropwise, and the mixture was added at room temperature for 1.5 minutes.
Stirred for hours. After the reaction, 50 ml of water containing 1 ml of concentrated hydrochloric acid was added, and the mixture was extracted with 50 ml of ether. Water layer 5
0 ml and then 30 ml of 4% aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure.
The obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane), and 0.75 g of methyl E-α-methoxyimino-2- (4-methylphenoxy) phenylacetate was obtained (yield: 78.1%). 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).

【００３２】参考例７ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸メチル１.０９g(０.004モル)に、乾燥ジメチルホルムア
ミド６mlおよび水酸化カリウム０.２９g(０.００４４モ
ル)を加え、１５分間室温撹拌した。ついで、乾燥トル
エン６mlを加え、さらに氷冷下でジメチル硫酸０.６１g
(０.００４４モル)を滴下した。滴下後２時間、室温撹
拌し、ついで、エーテル１００mlを加えて水洗を３回繰
り返した。エーテル層を無水硫酸マグネシウムで乾燥
し、減圧濃縮した。得られた残渣をシリカゲルクロマト
グラフィー(酢酸エチル／n−ヘキサン)で精製してＥ−
α−メトキシイミノ−２−フェノキシフェニル酢酸メチ
ル１.２０g(収率８０.６％)を無色結晶(融点１０９〜１
１０℃)として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:３.７８(s,３Ｈ)、４.０３
(s,３Ｈ)、６.８６〜７.４６(m,９Ｈ)。同様に、塩基お
よびメチル化剤をかえ、つぎの表に示す反応条件でも実
施した。Reference Example 7 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate To 1.09 g (0.004 mol) of methyl E-α-hydroxyimino-2-phenoxyphenylacetate was added 6 ml of dry dimethylformamide and 0.29 g (0.0044 mol) of potassium hydroxide 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 of dimethyl sulfate was further added under ice-cooling.
(0.0044 mol) was added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 2 hours, then, 100 ml of ether was added, and washing with water was repeated three 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 E-
1.20 g (yield: 80.6%) of methyl α-methoxyimino-2-phenoxyphenylacetate was obtained as colorless crystals (melting point: 109-1).
10 ° 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】[0033]

【表１】 参考例 塩基 メチル化剤 溶媒 反応 収率 (当量) (当量) 条件 (%) ８ 60%ＮaＨ Ｍe₂ＳＯ₄ ＴＨＦ ０℃ ９６.５ (１.１) (１.２) ６０分 ９ t−ＢuＯＫ Ｍe₂ＳＯ₄ ＴＨＦ ０℃ ８２.４ (１.３) (１.２) ３０分 １０ ＫＯＨ ＭeＩ ＤＭＦ/ 室温 ６６.６ (１.１) (１.２) ＰhＭe ２時間 t−Ｂu:t−ブチル、Ｍe:メチル、ＴＨＦ:テトラヒドロ
フラン、ＤＭＦ:ジメチルホルムアミド、ＰhＭe:トルエ
ン[Table 1] Reference Example Base Methylating agent Solvent Reaction Yield (equivalent) (equivalent) Condition (%) 8 60% NaH Me ₂ SO ₄ THF 0 ° C. 96.5 (1.1) (1.2) 60 minutes 9 t-BuOK Me ₂ SO ₄ THF 0 ° C. 82.4 (1.3) (1.2) 30 minutes 10 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

【００３４】参考例１１ Ｅ−α−メトキシイミノ−２−(４−メチルフェノキシ)
フェニル酢酸メチルの製造 Ｅ−α−ヒドロキシイミノ−２−(４−メチルフェノキ
シ)フェニル酢酸メチル０.７１g(０.００２５モル)を乾
燥テトラヒドロフラン１０mlに溶解後、６０％水素化ナ
トリウム０.１３g(０.００３３モル)を添加し、室温で
２０分撹拌し、氷冷下、ジメチル硫酸０.４４g(０.００
３５モル)を乾燥ＴＨＦ２.５mlに溶解した溶液を滴下
し、氷冷下、１時間４５分撹拌した。反応後、水を添加
し、濃塩酸でpＨ１に調整した。塩化メチレンで２回抽
出し、無水硫酸ナトリウムで乾燥し、減圧濃縮した。得
られた残渣をシリカゲルクロマトグラフィー(酢酸エチ
ル／n−ヘキサン)にて精製してＥ−α−メトキシイミノ
−２−(４−メチルフェノキシ)フェニル酢酸メチル０.
６１g(収率８１.３％)を無色油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.３２(s,３Ｈ)、３.７９
(s,３Ｈ)、４.０４(s,３Ｈ)、６.８５〜７.３９(m,８
Ｈ)。Reference Example 11 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. Extracted twice with methylene chloride, dried over anhydrous sodium 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- (4-methylphenoxy) phenylacetate.
61 g (81.3% yield) were 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).

【００３５】参考例１２ α−メトキシイミノ−２−フェノキシフェニルアセトニ
トリルの製造(Ｅ体とＺ体の混合物) α−ヒドロキシイミノ−２−フェノキシフェニルアセト
ニトリル(Ｅ体とＺ体の混合物)１.１９g(０.００５モ
ル)に、乾燥ジメチルホルムアミド１０mlおよび炭酸カ
リウム０.９０g(０.００６５モル)を加え、氷冷下でジ
メチル硫酸０.７６g(０.００６モル)を滴下した後、１.
５時間室温にて撹拌した。反応後、エーテル１５０mlを
加え、水１００mlで２回水洗した。エーテル層を無水硫
酸マグネシウムで乾燥し、減圧濃縮し、得られた残渣を
シリカゲルクロマトグラフィー(酢酸エチル／n−ヘキサ
ン)にて精製し、α−メトキシイミノ−２−フェノキシ
フェニルアセトニトリル１.１３g(収率８９.６％)を無
色油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:４.０３(s,０.７Ｈ)、４.１
７(s,２.３Ｈ)、６.８９〜７.６７(m,９Ｈ)。Reference Example 12 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 1.19 g of α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) (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 dimethyl sulfate was added dropwise under ice cooling.
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, concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate / n-hexane) to obtain 1.13 g of α-methoxyimino-2-phenoxyphenylacetonitrile (yield: 89.6%) 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).

【００３６】参考例１３ α−メトキシイミノ−２−フェノキシフェニルアセトニ
トリルの製造(Ｅ体とＺ体の混合物） α−ヒドロキシイミノ−２−フェノキシフェニルアセト
ニトリル（Ｅ体とＺ体の混合物)１.１９g(０.００５モ
ル)に、乾燥ジメチルホルムアミド１０mlおよび炭酸カ
リウム０.９０g(０.００６モル)を加え、氷冷下でヨウ
化メチル０.７８g(０.００５５mol)を滴下した後、４時
間室温にて撹拌した。反応後、エーテル１５０mlを加
え、水１００mlで２回水洗した。エーテル層を無水硫酸
マグネシウムで乾燥し、減圧濃縮した。得られた残渣を
シリカゲルクロマトグラフィー(酢酸エチル／n−ヘキサ
ン)で精製し、α−メトキシイミノ−２−フェノキシフ
ェニルアセトニトリル１.０６g(収率８４.０％)を無色
油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:４.０３(s,０.７Ｈ)、４.１
７(s,２.３Ｈ)、６.８９〜７.６９(m,９Ｈ)。Reference Example 13 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 1.19 g of α-hydroxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 0.005 mol), 10 ml of dry dimethylformamide and 0.90 g (0.006 mol) of potassium carbonate were added, and 0.78 g (0.0055 mol) of methyl iodide was added dropwise under ice-cooling, followed by 4 hours at room temperature. 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).

【００３７】参考例１４ α−メトキシイミノ−２−(４−クロロフェノキシ)フェ
ニルアセトニトリル(Ｅ体とＺ体の混合物)の製造 α−ヒドロキシイミノ−２−(４−クロロフェノキシ)フ
ェニルアセトニトリル(Ｅ体とＺ体の混合物)１.３６g
(０.００５モル)を乾燥ジメチルホルムアミド１０mlに
溶解し、炭酸カリウム０.９０g(０.００６５モル)を添
加し、氷冷下、ジメチル硫酸０.７６g(０.００６モル)
を添加し、室温で１時間撹拌した。エーテル１５０mlを
加え、２回水洗した。エーテル層を無水硫酸マグネシウ
ムで乾燥し、減圧濃縮して得られた残渣をシリカゲルク
ロマトグラフィー(酢酸エチル／n−ヘキサン)で精製
し、α−メトキシイミノ−２−(４−クロロフェノキシ)
フェニルアセトニトリル１.３５g(収率９４.４％)を淡
黄色油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:４.０２(s,０.６９Ｈ)、４.
１７(s,２.３１Ｈ)、６.９０〜７.６８(m,８Ｈ)。Reference Example 14 Preparation of α-methoxyimino-2- (4-chlorophenoxy) phenylacetonitrile (mixture of E-form and Z-form) α-hydroxyimino-2- (4-chlorophenoxy) phenylacetonitrile (E-form 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 the mixture was 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 give 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).

【００３８】実施例１ Ｅ−２−メトキシイミノ−Ｎ−メチル−２−(２−フェ
ノキシフェニル)アセトアミドの製造 Ｅ−２−ヒドロキシイミノ−Ｎ−メチル−２−(２−フ
ェノキシフェニル)アセトアミド１０.００g(０.０３７
モル)にアセトン２００ml、炭酸カリウム１５.３４g
(０.１１１モル)およびジメチル硫酸９.３３g(０.０７
４モル)を加え、室温で９時間撹拌した。反応後、濾過
し、アセトンで洗浄し、減圧濃縮した。得られた油状物
をトルエン５０mlに溶かし、１Ｎ水酸化ナトリウム水溶
液５０mlを加え、室温で３０分間撹拌した。トルエンで
抽出し、水洗し、減圧濃縮し、得られた残渣を再結晶
(メタノール／水)してＥ−２−メトキシイミノ−Ｎ−メ
チル−２−(２−フェノキシフェニル)アセトアミド９.
９３g(収率９４.４％)を無色結晶(融点８１.５〜８３
℃)として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.８７(d,３Ｈ,Ｊ＝５.０
Ｈz)、３.９１(s,３Ｈ)、６.６５(br.s,１Ｈ)、６.８７
〜７.３８(m,９Ｈ)。Example 1 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 mol) of dimethyl sulfate.
4 mol) and stirred at room temperature for 9 hours. After the reaction, the reaction solution was filtered, washed with acetone, and concentrated under reduced pressure. The obtained oil was dissolved in 50 ml of toluene, 50 ml of a 1N aqueous sodium hydroxide 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).

【００３９】実施例２ Ｅ−２−メトキシイミノ−Ｎ−メチル−２−[２−(４−
メチルフェノキシ)フェニル]アセトアミドの製造 Ｅ−２−ヒドロキシイミノ−Ｎ−メチル−２−[２−(４
−メチルフェノキシ)フェニル]アセトアミド１.００g
(０.００３５モル)を乾燥アセトン７mlに溶解し、炭酸
カリウム０.６３g(０.００４６モル)、ジメチル硫酸０.
５３g(０.００４２モル)を添加して室温で２２時間反応
させた。反応後、水を加え、塩化メチレンで２回抽出
し、無水硫酸ナトリウムで乾燥し、減圧濃縮した。得ら
れた残渣をシリカゲルクロマトグラフィー(酢酸エチル
／n−ヘキサン)で精製してＥ−２−メトキシイミノ−Ｎ
−メチル−２−[２−(４−メチルフェノキシ)フェニル]
アセトアミドの無色結晶０.９６g(収率９２.３％)を得
た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.２９(s,３Ｈ)、２.８１
(d,３Ｈ,Ｊ＝４.９Ｈz)、３.８９(s,３Ｈ)、６.７１(b
r.s,１Ｈ)、６.８２(d,１Ｈ,Ｊ＝８.１Ｈz)、６.８９〜
６.９２(m,２Ｈ)、７.０５〜７.１０(m,３Ｈ)、７.２３
〜７.３１(m,２Ｈ)。Example 2 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, 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 H NMR (CDCl ₃ ) δ ppm: 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).

【００４０】参考例１５ Ｅ−２−ヒドロキシイミノ−Ｎ−メチル−２−(２−フ
ェノキシフェニル)アセトアミドの製造 粗製Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニ
ル酢酸メチル３９.６０g(純度５１.２％、０.０７４７
モル)に、メタノール１００mlおよび４０％メチルアミ
ン水溶液１５.４５g(０.１９９モル)を加えて室温１５
時間撹拌した。ついで、４０％メチルアミン水溶液７.
７３g(０.０９９５モル)を加え、７０℃の油浴中で６時
間撹拌した。反応後、水２００mlおよびトルエン１００
mlを加え、１時間氷冷撹拌した。析出晶を濾取し、再結
晶(メタノール／トルエン)してＥ−２−ヒドロキシイミ
ノ−Ｎ−メチル−２−(２−フェノキシフェニル)アセト
アミド１２.３１g(収率６０.１％)を無色結晶(融点１８
３〜１８４.５℃)として得た。¹ ＨＮＭＲ(d₆−ＤＭＳＯ)δppm:２.６５(d,３Ｈ,Ｊ＝
４.５Ｈz)、６.３０〜７.４７(m,９Ｈ)、７.９２(m,１
Ｈ,Ｊ＝４.５Ｈz)。Reference Example 15 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 a 70 ° C. oil bath for 6 hours. After the reaction, 200 ml of water and 100 ml of toluene
ml was added and the mixture was stirred under 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).

【００４１】参考例１６ Ｅ−２−ヒドロキシイミノ−Ｎ−メチル−２−[２−(４
−メチルフェノキシ)フェニル]アセトアミドの製造 Ｅ−α−ヒドロキシイミノ−２−(４−メチルフェノキ
シ)フェニル酢酸メチル１.００g(０.００３５モル)をメ
タノール７mlに溶解し、４０％メチルアミンメタノール
溶液０.５４g(０.００７モル)を添加し、７０分間還流
した。さらに４０％メチルアミンメタノール溶液１.３
６g(０.０１７５モル)を添加し、３時間還流した。反応
後、減圧濃縮してＥ−２−ヒドロキシイミノ−Ｎ−メチ
ル−２−[２−(４−メチルフェノキシ)フェニル]アセト
アミド１.００g(収率１００.０％)をアモルファスとし
て得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:２.３１(s,３Ｈ)、２.８６
(d,３Ｈ,Ｊ＝５.９Ｈz)６.６０(br.s,１Ｈ)、６.８４〜
７.３６(m,８Ｈ)、７.９３(br.s,１Ｈ)。Reference Example 16 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, and a 40% methylamine methanol solution 0 was dissolved. .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).

【００４２】参考例１７ Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸の製造 Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸メチル９.９９g(０.0368モル)に、メタノール３６.８m
l、水酸化ナトリウム３.２３g(０.０８１モル)および水
３６.８mlを加えて、１時間加熱還流した。加熱後、氷
冷下で濃塩酸１１mlを加え、析出した結晶を濾取し、再
結晶(メタノール／酢酸エチル／n−ヘキサン)してα−
ヒドロキシイミノ−２−フェノキシフェニル酢酸６.９
０g(収率７２.９％)を無色結晶(分解１８０℃)として得
た。¹ ＨＮＭＲ(d₆−ＤＭＳＯ)δppm:６.８３〜７.３８(m,９
Ｈ)、１２.２６(br.s,１Ｈ)、１２.８５(br.s,１Ｈ)。REFERENCE EXAMPLE 17 Preparation of E-α-hydroxyimino-2-phenoxyphenylacetic acid To 9.99 g (0.0368 mol) of methyl E-α-hydroxyimino-2-phenoxyphenylacetate was added 36.8 ml of methanol.
l, 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 α-
Hydroxyimino-2-phenoxyphenylacetic acid 6.9
0 g (72.9% yield) were 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).

【００４３】参考例１８ Ｅ−α−ヒドロキシイミノ−２−(４−メチルフェノキ
シ)フェニル酢酸の製造 Ｅ−α−ヒドロキシイミノ−２−(４−メチルフェノキ
シ)フェニル酢酸メチル１.００g(０.００３５モル)にメ
タノール３.５ml、水３.５ml、水酸化ナトリウム０.３
１g(０.００７７モル)を添加し、１時間加熱還流を行っ
た。室温まで冷却後、５％塩酸水溶液でpＨ１に調整
し、室温にて撹拌後、結晶を濾取し、水洗してα−ヒド
ロキシイミノ−２−(４−メチルフェノキシ)フェニル酢
酸の無色結晶０.９０g(収率９４.７％)を得た。¹ ＨＮＭＲ(d₆−ＤＭＳＯ)δppm:２.２７(s,３Ｈ)、６.
７８〜７.３７(m,８Ｈ)。REFERENCE EXAMPLE 18 Preparation of E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetic acid 1.00 g of methyl E-α-hydroxyimino-2- (4-methylphenoxy) phenylacetate (0.0035) Mol) in 3.5 ml of methanol, 3.5 ml of water, 0.3 ml of sodium hydroxide.
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 hydrochloric acid solution, and the mixture was stirred at room temperature. The crystals were collected by filtration, washed with water, and washed with colorless crystals of α-hydroxyimino-2- (4-methylphenoxy) phenylacetic acid. 90 g (94.7% yield) were obtained. ¹ H NMR (d ₆ -DMSO) δ ppm: 2.27 (s, 3H), 6.
78-7.37 (m, 8H).

【００４４】参考例１９ α−ヒドロキシイミノ−２−フェノキシフェニルアセト
ニトリル(Ｅ体とＺ体の混合物)の製造 無水エタノール１５mlに、ナトリウム０.５５g(０.０２
４モル)を溶解し、０℃以下で２−フェノキシフェニル
アセトニトリル４.１８g(０.０２モル)および無水エタ
ノール３mlの混合物を７分間で滴下した。さらに、亜硝
酸イソアミル３.５１g(０.０３モル)を０℃以下にて１
０分間で滴下し、２４時間室温にて撹拌した。反応後、
５％塩酸水溶液１００mlを加えてエーテルで抽出し、無
水硫酸マグネシウムで乾燥した。減圧濃縮して得られた
粗製物をシリカゲルクロマトグラフィー(酢酸エチル／n
−ヘキサン)で精製して、α−ヒドロキシイミノ−２−
フェノキシフェニルアセトニトリル４.５３g(収率９５.
１％)を低融点の結晶として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:６.８３〜７.６７(m,９
Ｈ)、８.６８(br.s,０.２５Ｈ)、９.０２(br.s,０.７５
Ｈ)。Reference Example 19 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 absolute 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).

【００４５】参考例２０ α−ヒドロキシイミノ−２−(４−クロロフェノキシ)フ
ェニルアセトニトリル(Ｅ体とＺ体の混合物)の製造 無水エタノール２５mlに金属ナトリウム０.９７g(０.０
４２モル)を添加し、溶解後、氷冷下、２−(４−クロロ
フェノキシ)フェニルアセトニトリル８.５３g(０.０３
５モル)を無水エタノール７mlの溶液を滴下した。つい
で、亜硝酸イソアミル６.１５g(０.０５２５モル)を滴
下し、２.５時間室温で反応させた後、水を加え、濃塩
酸でpＨ１に調整し、エーテルで抽出し、水洗し、無水
硫酸マグネシウムで乾燥した。エーテルを減圧濃縮し、
得られた残渣をシリカゲルクロマトグラフィー(酢酸エ
チル／n−ヘキサン)で精製して、α−ヒドロキシイミノ
−２−(４−クロロフェノキシ)フェニルアセトニトリル
９.０３g(収率９４.６％)を淡褐色粘稠液体として得
た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:６.９０〜７.６８(m,８
Ｈ)、９.１２(br.s,０.２８Ｈ)、９.４６(br.s,０.７２
Ｈ)。Reference Example 20 Preparation of α-hydroxyimino-2- (4-chlorophenoxy) phenylacetonitrile (mixture of E-form and Z-form) 0.97 g (0.00 g) of metallic sodium was added to 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).

【００４６】参考例２１ Ｅ−α−ヒドロキシイミノ−２−フェノキシフェニル酢
酸の製造 α−ヒドロキシイミノ−２−フェノキシフェニルアセト
ニトリル(Ｅ体とＺ体の混合物)０.７１g(０.００３モ
ル)に、エタノール３ml、水酸化カリウム０.４０g(０.
００７２モル)および水３mlを加え、２４時間加熱還流
した。反応後、塩化メチレン１０mlと１０％塩酸水溶液
を加え、析出したα−ヒドロキシイミノ−２−フェノキ
シフェニル酢酸の結晶を濾取し、無色結晶０.４７g(収
率６０.９％)を得た。¹ ＨＮＭＲ(d₆−ＤＭＳＯ)δppm:６.８３〜７.３８(m,９
Ｈ)、１２.２６(br.s,１Ｈ)、１２.８５(br.s,１Ｈ)。Reference Example 21 Preparation of E-α-hydroxyimino-2-phenoxyphenylacetic acid To 0.71 g (0.003 mol) of α-hydroxyimino-2-phenoxyphenylacetonitrile (a mixture of E-form and Z-form) was prepared. 3 ml of ethanol and 0.40 g of potassium hydroxide (0.4 g)
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).

【００４７】参考例２２ ２−フェノキシベンズアルドオキシムの製造 ２−フェノキシベンズアルデヒド４.９６g(０.０２５モ
ル)に、無水メタノール５０mlおよび塩酸ヒドロキシル
アミン２.０８g(０.０３モル)を加えて６０℃にて３時
間撹拌した。反応後、水２００mlを加え、塩化メチレン
で抽出し、硫酸マグネシウムで乾燥した。減圧濃縮して
得られた粗製物をシリカゲルクロマトグラフィー(酢酸
エチル／n−ヘキサン)で精製して２−フェノキシベンズ
アルドオキシム３.９５g(収率７４.１％)を無色油状物
として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:６.８８〜７.４１(m,８
Ｈ)、７.４５(s,１Ｈ)、７.８６(dd,１Ｈ,Ｊ＝７.９,
２.０)８.４９(s,１Ｈ)。Reference Example 22 Preparation of 2-phenoxybenzaldoxime To 4.96 g (0.025 mol) of 2-phenoxybenzaldehyde were added 50 ml of anhydrous methanol and 2.08 g (0.03 mol) of hydroxylamine hydrochloride at 60 ° C. 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).

【００４８】参考例２３ α−メトキシイミノ−２−フェノキシフェニルアセトニ
トリル(Ｅ体とＺ体の混合物)の製造 ２−フェノキシベンズアルドキシム１.０７g(０.００５
モル)に、乾燥エーテル１０mlを加え、−１０℃以下で
塩素０.４６g(０.００６５モル)を導入した後、０℃に
て５時間撹拌した。反応後、反応液を減圧濃縮し、得ら
れた残渣に、乾燥塩化メチレン１０mlおよびテトラエチ
ルアンモニウムシアニド０.８６g(０.００５５モル)を
加え、室温にて一夜撹拌した。反応後、水１５０mlを加
えて塩化メチレンで抽出し、無水硫酸マグネシウムで乾
燥後、シリカゲルクロマトグラフィー(酢酸エチル／n−
ヘキサン)で精製して得られたα−ヒドロキシイミノ−
２−フェノキシフェニルアセトニトリルの粗製物０.５
１gに、乾燥ジメチルホルムアミド４mlおよび炭酸カリ
ウム０.３６g(０.００２６ml)を加えた。さらに氷冷下
で硫酸ジメチル０.３０g(０.００２４モル)を加えた
後、室温２時間撹拌した。反応後、エーテル１００mlを
加え、２回水洗し、無水硫酸マグネシウムで乾燥後、減
圧濃縮した。得られた粗製物をシリカゲルクロマトグラ
フィー(酢酸エチル／n−ヘキサン)で精製し、α−メト
キシイミノ−２−フェノキシフェニルアセトニトリル
０.２１g(収率１６.６％)を無水油状物として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:４.０３(s,０.７Ｈ)、４.１
７(s,２.３Ｈ)、６.８９〜７.６７(m,９Ｈ)。Reference Example 23 Production of α-methoxyimino-2-phenoxyphenylacetonitrile (mixture of E-form and Z-form) 1.07 g (0.005 g) of 2-phenoxybenzaldoxime
Mol), 0.46 g (0.0065 mol) of chlorine was introduced at -10 ° C or lower, followed by stirring at 0 ° C for 5 hours. After the reaction, the reaction solution was concentrated under reduced pressure, 10 ml of dry methylene chloride and 0.86 g (0.0055 mol) of tetraethylammonium cyanide were added to the obtained residue, and the mixture was stirred at room temperature overnight. After the reaction, 150 ml of water was added, extracted with methylene chloride, dried over anhydrous magnesium sulfate, and then subjected to silica gel chromatography (ethyl acetate / n-ethyl acetate).
Α-hydroxyimino-
Crude of 2-phenoxyphenylacetonitrile 0.5
To 1 g was added 4 ml of dry dimethylformamide and 0.36 g (0.0026 ml) of potassium carbonate. After further adding 0.30 g (0.0024 mol) of dimethyl sulfate under ice cooling, 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).

【００４９】参考例２４ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 n−ブチルリチウム(１.６２モルヘキサン溶液)５００ml
(０.８１モル)に、５℃以下でジフェニルエーテル２０
６.８１g(１.２１５モル)および乾燥テトラヒドロフラ
ン４０５mlの混合液を４０分間にわたって滴下し、室温
で２４時間撹拌した。反応後、乾燥テトラヒドロフラン
８１０mlにシュウ酸ジメチル１１８.０９g(１.２１５モ
ル)を溶解した撹拌溶液に、０℃以下で５０分間にわた
って滴下し、室温で２４時間撹拌した。反応後、氷水２
lを加え、トルエン５００mlで抽出し、さらに抽出液を
水洗し、無水硫酸ナトリウムで乾燥し、減圧濃縮して褐
色油状物３０２.９４gを得た。この油状物に、メタノー
ル１.３lおよび塩酸ヒドロキシルアミン４７.２５g(０.
６８モル)を加えて１時間加熱還流し、ついで、水４５
０mlに水酸化ナトリウム７９.２g(１.９８モル)を溶解
した溶液を加えて１時間加熱還流した。反応後、メタノ
ールを減圧留去し、水１.８lを加え、塩化メチレン１l
で２回洗浄し、水層に濃塩酸をpＨ２以下になるまで加
え、析出した結晶を濾取し、Ｅ−α−ヒドロキシイミノ
−２−フェノキシフェニル酢酸の粗結晶１４１.５５g
(収率６８.０％ n−ブチルリチウムより)を得た。得ら
れた粗結晶２５.７３g(０.１モル)に、乾燥ジメチルホ
ルムアミド１５０mlおよび８５％水酸化カリウム１４.
５２g(０.２２モル)を加え、熱時溶解し、乾燥トルエン
１５０mlを加え、硫酸ジメチル２７.７５g(０.２２モ
ル)を２５〜３０℃で５分間にわたって滴下し、室温で
１.５時間撹拌した。反応後、１％塩酸水溶液７００ml
を加え、トルエン５００mlで抽出し、抽出液を２％炭酸
水素ナトリウム水溶液で水洗して無水硫酸ナトリウムで
乾燥した。減圧濃縮して得られた粗製物を再結晶(メタ
ノール)して精製し、Ｅ−α−メトキシイミノ−２−フ
ェノキシフェニル酢酸メチル２１.１５g(収率７４.１
％)を無色結晶(融点１０９〜１１０℃)として得た。¹ ＨＮＭＲ(ＣＤＣl₃)δppm:３.７８(s,３Ｈ)、４.０３
(s,３Ｈ)、６.８６〜７.４６(m,９Ｈ)。Reference Example 24 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 500 ml of n-butyllithium (1.62 mol hexane solution)
(0.81 mol) in diphenyl ether 20
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, a stirred solution of 118.09 g (1.215 mol) of dimethyl oxalate dissolved in 810 ml of dry tetrahydrofuran was added dropwise at 0 ° C. or lower over 50 minutes, and the mixture was stirred at room temperature for 24 hours. After the reaction, ice water 2
l, and the mixture was extracted with 500 ml of toluene. The extract was further 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).

【００５０】参考例２５ Ｅ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチルの製造 Ｚ−α−メトキシイミノ−２−フェノキシフェニル酢酸
メチル０.２９g(１.０mmol)に、乾燥メタノール３mlと
１０％塩酸メタノール溶液０.３６g(１.０mmol)を加
え、６時間加熱還流して異性化を行った。反応後、減圧
留去して得られた残渣０.２９gはＥ異性体とＺ異性体の
純粋な混合物であり、その生成比は７７.６:２２.４で
あった(ＮＭＲ定量)。Reference Example 25 Preparation of methyl E-α-methoxyimino-2-phenoxyphenylacetate 0.29 g (1.0 mmol) of methyl Z-α-methoxyimino-2-phenoxyphenylacetate was mixed with 3 ml of dry methanol and 10% 0.36 g (1.0 mmol) of a methanol solution of hydrochloric acid was added, and the mixture was refluxed for 6 hours to effect isomerization. After the reaction, 0.29 g of a residue obtained by distillation under reduced pressure was a pure mixture of the E isomer and the Z isomer, and the production ratio was 77.6: 22.4 (NMR quantification).

【００５１】参考例２６ Ｅ−２−メトキシイミノ−Ｎ−メチル−２−(２−フェ
ノキシフェニル)アセトアミドの製造 Ｚ−２−メトキシイミノ−Ｎ−メチル−２−(２−フェ
ノキシフェニル)アセトアミド０.２８g(１.０mmol)に、
乾燥メタノール３mlと１０％塩酸メタノール溶液０.３
６g(１.０mmol)を加え、６時間加熱還流して異性化を行
った。反応後、減圧留去して得られた残渣０.２８gはＥ
異性体とＺ異性体の純粋な混合物であり、その生成比は
９１.５:８.５であった(ＮＭＲ定量)。Reference Example 26 Preparation of E-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide Z-2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) acetamide 28 g (1.0 mmol)
3 ml of dry methanol and 0.3% of 10% hydrochloric acid in methanol
6 g (1.0 mmol) was added, and the mixture was refluxed for 6 hours to effect isomerization. After the reaction, 0.28 g of a residue obtained by distillation under reduced pressure was E
It was a pure mixture of the isomers and the Z isomer, with a production ratio of 91.5: 8.5 (NMR quantification).

【００５２】[0052]

【発明の効果】本発明によれば、農業用殺菌剤として有
用なメトキシイミノアセトアミド化合物の経済的かつ副
生物生成の少ない製造法が提供される。According to the present invention, there is provided an economical process for producing a methoxyiminoacetamide compound which is useful as an agricultural fungicide, and which produces little by-product.

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.⁶ 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｃ 255/64 Ｃ０７Ｃ 255/64 (72)発明者 長井 正彦 兵庫県尼崎市杭瀬南新町４−４−８− 608 (56)参考文献 特開 昭63−30463（ＪＰ，Ａ)──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location C07C 255/64 C07C 255/64 (72) Inventor Masahiko Nagai 4-4-4 Minase Shinmachi, Amagasaki City, Hyogo Prefecture 8-608 (56) References JP-A-63-30463 (JP, A)

Claims (1)

(57)【特許請求の範囲】(57) [Claims] 【請求項１】 式[Ｖ]: 【化１】 [式中、Ｘは水素、低級アルキル、低級アルコキシまた
はハロゲン、Ｍは水素またはアルカリ金属、および〜は
Ｅ体、Ｚ体またはＥ体とＺ体の混合物のいずれかの配置
を意味する]で示される化合物を、式: ＣＨ₃−Ｌ [ＩＶ] [式中、Ｌはハロゲンまたは−ＯＳＯ₂ＯＣＨ₃を意味す
る]で示される化合物と反応させることを特徴とする式
[Ｉ]: 【化２】 [式中、Ｘおよび〜は前記と同意義である]で示される化
合物の製造法。(1) Formula [V]: [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.
[I]: [Wherein X and-are the same as defined above].