JPH0822853B2 - Pyrazole-4-carboxylic acids and method for producing the same - Google Patents
Pyrazole-4-carboxylic acids and method for producing the sameInfo
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- JPH0822853B2 JPH0822853B2 JP62266612A JP26661287A JPH0822853B2 JP H0822853 B2 JPH0822853 B2 JP H0822853B2 JP 62266612 A JP62266612 A JP 62266612A JP 26661287 A JP26661287 A JP 26661287A JP H0822853 B2 JPH0822853 B2 JP H0822853B2
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- formula
- pyrazole
- carboxylic acid
- alkyl group
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Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は農園芸用殺菌剤の中間体は、すなわち、農園
芸用殺菌剤として優れた幅広い植物病害防除効果を有
し、特に各種作物の疫病、べと病に対しては予防的に
も、また病害に感染した後の治療的にも優れた防除効果
を示す一般式（VII） （式中、R1はアルキル基、アルケニル基、ハロアルケニ
ル基、フェニル基またはカルバモイル基を示し、R2は水
素原子、アルキル基、ハロアルキル基またはフェニル基
を示し、R3は水素原子、ハロゲン原子、低級アルキル基
またはフェニル基を示し、R4およびR5はそれぞれ水素原
子または低級アルキル基を示す） で表されるピラゾール誘導体（特願昭62-85653（特開昭
63-45264号公報参照））の中間体として有用な一般式
（Ｉ） （式中、R1は炭素数１〜８のアルキル基、フルオロアル
キル基、アリル基、ハロアリル基またはメチルカーバモ
イル基を示し、R2は水素原子、炭素数１〜３のアルキル
基またはフルオロアルキル基を示す。但し、R1およびR2
が共にメチル基である場合は除く） で示されるピラゾール−４−カルボン酸誘導体およびそ
の製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention is an intermediate of a fungicide for agricultural and horticultural use, that is, it has an excellent effect of controlling a wide range of plant diseases as a fungicide for agricultural and horticultural use, and particularly for various crops. A general formula (VII) showing an excellent control effect against epidemics and downy mildews as well as therapeutically after infection with diseases. (In the formula, R 1 represents an alkyl group, an alkenyl group, a haloalkenyl group, a phenyl group or a carbamoyl group, R 2 represents a hydrogen atom, an alkyl group, a haloalkyl group or a phenyl group, and R 3 represents a hydrogen atom or a halogen atom. , A lower alkyl group or a phenyl group, and R 4 and R 5 each represent a hydrogen atom or a lower alkyl group) (Japanese Patent Application No. 62-85653).
No. 63-45264), which is useful as an intermediate of formula (I) (In the formula, R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and R 2 is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or fluoroalkyl. Group, provided that R 1 and R 2
When both are methyl groups), and a process for producing the same.
前記一般式（VII）の中間体としては1,3−ジメチルピ
ラゾール−４−カルボン酸エステルが知られているだけ
で、またその製造方法については、オーストラリアン
ジャーナル オブ ケミストリー（Aust.J.Chem.）第36
巻、135〜147ページ（1983）に３（５）−メチルピラゾ
ール−４−カルボン酸エステルとヨウ化メチルをアルコ
ール中、金属アルコラートの存在下反応させ、1,3−ジ
メチルピラゾール−４−カルボン酸エステルと1,5−ジ
メチルピラゾール−４−カルボン酸エステルの1/1混合
物を得たと報告されている。本発明者らは、上記記載の
合成条件に従って反応を行った結果、1,3−ジメチルピ
ラゾール−４−カルボン酸エステルと1,5−ジメチルピ
ラゾール−４−カルボン酸エステルを生成比4/6の混合
物で得た。この方法では目的とする1,3−ジメチルピラ
ゾール−４−カルボン酸エステルの生成比が悪く、高価
なアルキル化剤、金属アルコラート等を用いるため、製
造コストが高くなる問題点が挙げられる。Only 1,3-dimethylpyrazole-4-carboxylic acid ester is known as an intermediate of the above general formula (VII).
Journal of Chemistry (Aust.J.Chem.) No. 36
Vol. 135-147 (1983), 3 (5) -methylpyrazole-4-carboxylic acid ester and methyl iodide were reacted in alcohol in the presence of metal alcoholate to give 1,3-dimethylpyrazole-4-carboxylic acid. It is reported that a 1/1 mixture of the ester and 1,5-dimethylpyrazole-4-carboxylic acid ester was obtained. As a result of carrying out the reaction according to the synthesis conditions described above, the present inventors have produced 1,3-dimethylpyrazole-4-carboxylic acid ester and 1,5-dimethylpyrazole-4-carboxylic acid ester with a production ratio of 4/6. Obtained as a mixture. In this method, the production ratio of the target 1,3-dimethylpyrazole-4-carboxylic acid ester is low, and since an expensive alkylating agent, metal alcoholate, or the like is used, the production cost becomes high.
本発明は重要な農園芸用殺菌剤である前記一般式（VI
I）で表されるピラゾール誘導体の中間体として有用な
一般式（Ｉ）で示される新規なピラゾール−４−カルボ
ン酸誘導体およびその製造法を提供することを課題とす
る。The present invention provides the general formula (VI) which is an important agricultural and horticultural fungicide.
An object of the present invention is to provide a novel pyrazole-4-carboxylic acid derivative represented by the general formula (I) which is useful as an intermediate for the pyrazole derivative represented by I), and a method for producing the same.
前記課題を解決すべく鋭意検討した結果、反応式Ａお
よびＢに示された経路で容易にピラゾール−４−カルボ
ン酸誘導体が容易に得られることを見出し本発明を完成
した。As a result of intensive studies to solve the above-mentioned problems, the inventors have found that a pyrazole-4-carboxylic acid derivative can be easily obtained by the routes shown in reaction formulas A and B, and completed the present invention.
すなわち、本発明は一般式（Ｉ） （式中、R1は炭素数１〜８のアルキル基、フルオロアル
キル基、アリル基、ハロアリル基またはメチルカーバモ
イル基を示し、R2は水素原子、炭素数１〜３のアルキル
基またはフルオロアルキル基を示す。但し、R1およびR2
が共にメチル基である場合は除く） で示されるピラゾール−４−カルボン酸誘導体、 および一般式（II） R1−NHNH2 （II） （式中、R1は炭素数１〜４のアルキル基を示す） で示されるヒドラジン類と一般式（III） （式中、R2は前記の意味を示し、Ｒは低級アルキル基を
示す） で示されるエトキシメチレンアシル酢酸エステル類を反
応させ、一般式（IV） （式中、R1、は炭素数１〜４のアルキル基を示し、R2お
よびＲは前記の意味を示す）で示されるピラゾール−４
−カルボン酸エステル類とした後、水酸化アルカリで加
水分解することを特徴とする前記一般式（Ｉ）で示され
るピラゾール−４−カルボン酸誘導体の製造方法、およ
び一般式（III） （式中、R2およびＲは前記の意味を示す） で示されるエトキシメチレンアシル酢酸エステル類と抱
水ヒドラジンと反応させ、一般式（Ｖ） （式中、R2およびＲは前記の意味を示す） で示される１（２）−Ｈ−ピラゾール−４−カルボン酸
エステル類とし、塩基の存在下に一般式（VI） R1X （VI） （式中、R1は炭素数１〜８のアルキル基、フルオロアル
キル基、アリル基、ハロアリル基またはメチルカーバモ
イル基を示し、Ｘはハロゲン原子を示す） で示されるハロゲン化物を反応させて一般式（IV） （式中、R1は炭素数１〜８のアルキル基、フルオロアル
キル基、アリル基、ハロアリル基またはメチルカーバモ
イル基を示し、R2およびＲは前記の意味を示す） で示されるピラゾール−４−カルボン酸エステル類とし
た後、水酸化アルカリで加水分解することを特徴とする
前記一般式（Ｉ）で示されるピラゾール−４−カルボン
酸誘導体の製造方法である。That is, the invention has the general formula (I) (In the formula, R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and R 2 is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or fluoroalkyl. Group, provided that R 1 and R 2
When both are methyl groups), and a pyrazole-4-carboxylic acid derivative represented by the general formula (II) R 1 —NHNH 2 (II) (wherein R 1 is an alkyl group having 1 to 4 carbon atoms). ) And the general formula (III) (In the formula, R 2 has the above-mentioned meaning and R represents a lower alkyl group), ethoxymethylene acyl acetic acid ester represented by the following formula (IV) (In the formula, R 1 represents an alkyl group having 1 to 4 carbon atoms, and R 2 and R have the above-mentioned meaning).
-A method for producing a pyrazole-4-carboxylic acid derivative represented by the above general formula (I), characterized in that it is hydrolyzed with an alkali hydroxide after forming a carboxylic acid ester, and the general formula (III) (Wherein R 2 and R have the above meanings) and ethoxymethylene acyl acetic acid ester represented by the formula (V) is reacted with hydrazine hydrate. (In the formula, R 2 and R have the above-mentioned meanings) 1 (2) -H-pyrazole-4-carboxylic acid ester represented by the formula (VI) R 1 X (VI ) (Wherein R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and X represents a halogen atom). General formula (IV) (In the formula, R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and R 2 and R have the above-mentioned meanings) -A method for producing a pyrazole-4-carboxylic acid derivative represented by the above general formula (I), which comprises hydrolyzing with a carboxylic acid ester and then with an alkali hydroxide.
本発明のピラゾール−４−カルボン酸誘導体は新規化
合物であり、前記一般式（VII）で表されるピラゾール
誘導体の中間体として有用である。The pyrazole-4-carboxylic acid derivative of the present invention is a novel compound and is useful as an intermediate for the pyrazole derivative represented by the general formula (VII).
本発明方法は下記反応式ＡおよびＢに示される経路に
より行われる。The method of the present invention is carried out by the routes shown in the following reaction formulas A and B.
参考文献 Aust.J.Chem,36,135-147（1983） 本反応について詳細に説明する。ヒドラジン類（II）
とエトキシメチレンアシル酢酸エステル類（III）を無
溶媒又は不活性な溶媒中で加熱する。モル比はどちらか
が過剰でも反応は進行するが、両者等モルで反応させる
のが経済的な面から望ましい。反応温度は室温から溶媒
の還流温度まで可能であるが、70〜100℃で行うのが望
ましい。溶媒としてはアルコール類、テトラヒドロフラ
ンおよびジオキサン等のエーテル類、ベンゼン、トルエ
ン、キシレン、クロロベンゼンおよびジクロロベンゼン
等の芳香族類、ハロゲン化炭化水素類、N,N−ジメチル
ホルムアミド等の非プロトン性極性溶媒等が挙げられ
る。反応時間は２〜10時間であり３〜５時間で完結する
ことが多い。反応終了後、減圧蒸留またはカラムクロマ
トグラフィーにより精製することができるが、通常は粗
製のまま次の加水分解を行う。 References Aust. J. Chem, 36, 135-147 (1983) This reaction will be described in detail. Hydrazines (II)
And ethoxymethylene acyl acetates (III) are heated in a solvent-free or inert solvent. The reaction proceeds even if either of the molar ratios is excessive, but it is desirable from the economical point of view to react the two in equimolar amounts. The reaction temperature may range from room temperature to the reflux temperature of the solvent, but is preferably 70 to 100 ° C. As the solvent, alcohols, ethers such as tetrahydrofuran and dioxane, aromatics such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, halogenated hydrocarbons, aprotic polar solvents such as N, N-dimethylformamide, etc. Is mentioned. The reaction time is 2 to 10 hours and is often completed in 3 to 5 hours. After completion of the reaction, it can be purified by distillation under reduced pressure or column chromatography, but usually, the following hydrolysis is carried out in a crude state.
加水分解は水酸化アルカリ水溶液中で加熱することに
より容易に行うことができる。反応温度は50℃から還流
点であるが、還流点で行うのが望ましい。反応終了後冷
却し、酸を加えてpH4〜５にすると目的のピラゾール−
４−カルボン酸が析出してくる。濾取あるいは溶媒で抽
出することにより目的物を得ることができる。通常は水
から再結晶して精製品を得る。Hydrolysis can be easily performed by heating in an aqueous solution of alkali hydroxide. The reaction temperature is from 50 ° C. to the reflux point, but it is preferably carried out at the reflux point. After the reaction is complete, the reaction mixture is cooled, and acid is added to adjust the pH to 4-5.
4-carboxylic acid precipitates. The target product can be obtained by filtration or extraction with a solvent. It is usually recrystallized from water to obtain a purified product.
反応式Ａの第一工程と全く同様にして１（２）−Ｈ−
ピラゾール−４−カルボン酸エステル類（Ｖ）が得られ
る。次に塩基の存在下ハロゲン化物（VI）を加え加熱す
るとピラゾール−４−カルボン酸エステル類（IV）が得
られる。塩基としてはアルカリ金属のアルコラート類、
水酸化アルカリ、炭酸アルカリ及びトリエチルアミンや
ピリジンの様な有機塩基が挙げられる。溶媒としてはア
ルコール類、エーテル類、芳香族炭化水素類、ハロゲン
化炭化水素類あるいはN,N−ジメチルホルムアミドの様
な非プロトン性極性溶媒等が挙げられる。この反応は50
℃から還流点までの温度で行い得る。この際、目的の1,
3−ジ置換ピラゾール−４−カルボン酸エステル類の他
に1,5−ジ置換ピラゾール−４−カルボン酸エステル類
が副生するが、混合物のまま加水分解しピラゾール−４
−カルボン酸として再結晶により分離することができ
る。 In the same manner as in the first step of Reaction formula A, 1 (2) -H-
Pyrazole-4-carboxylic acid esters (V) are obtained. Next, a halide (VI) is added in the presence of a base and heated to obtain a pyrazole-4-carboxylic acid ester (IV). As the base, alkali metal alcoholates,
Examples include alkali hydroxides, alkali carbonates and organic bases such as triethylamine and pyridine. Examples of the solvent include alcohols, ethers, aromatic hydrocarbons, halogenated hydrocarbons, aprotic polar solvents such as N, N-dimethylformamide, and the like. This reaction is 50
It can be carried out at a temperature from 0 ° C to the reflux point. At this time, the purpose of 1,
In addition to 3-di-substituted pyrazole-4-carboxylic acid esters, 1,5-di-substituted pyrazole-4-carboxylic acid esters are by-produced, but they are hydrolyzed as a mixture to give pyrazole-4
Can be separated by recrystallization as the carboxylic acid.
加水分解については反応式Ａと全く同様に行うことが
できる。The hydrolysis can be performed in exactly the same manner as in reaction formula A.
本発明方法によれば容易に目的物を得ることが出来
る。According to the method of the present invention, the target product can be easily obtained.
本発明の化合物を中間体とする農園芸用殺菌剤は以下
の反応式に従って製造される。The agricultural and horticultural fungicide containing the compound of the present invention as an intermediate is produced according to the following reaction formula.
（式中、R1,R2,R3,R4およびR5はそれぞれ前記の意味を
示す。） 一般式（VIII）で表わされるアルデヒドをHCNおよび
アンモニアの存在下にシュトレッカー反応を行いα−ア
ミノブテンニトリル誘導体（IX）を得る。次いでこれを
塩基の存在下、予めピラゾールカルボン酸（Ｉ）と塩化
チオニルで調製したピラゾールカルボン酸クロリド
（Ｘ）と反応させる。この反応は溶媒または希釈剤中で
行うのが好ましい。溶媒としては本反応に不活性なもの
はいずれも使用できる。この反応は中間体のα−アミノ
ブテンニトリル誘導体（IX）の熱安定性がよくないた
め、あまり高温下での反応は望ましくなく、また発熱反
応であるため冷却下（０〜５℃）に行うことが望まし
い。 (In the formula, R 1 , R 2 , R 3 , R 4 and R 5 each have the above-mentioned meaning.) The aldehyde represented by the general formula (VIII) is subjected to a Strecker reaction in the presence of HCN and ammonia to obtain α -Aminobutenenitrile derivative (IX) is obtained. This is then reacted in the presence of a base with pyrazolecarboxylic acid (I) and pyrazolecarboxylic acid chloride (X) previously prepared with thionyl chloride. This reaction is preferably carried out in a solvent or diluent. Any solvent that is inert to this reaction can be used as the solvent. This reaction is not desirable because the thermal stability of the intermediate α-aminobutenenitrile derivative (IX) is not good, and it is an exothermic reaction, and is performed under cooling (0 to 5 ° C). Is desirable.
本発明に係る化合物から誘導される前記一般式（VI
I）で表わされるピラゾール誘導体は広い範囲の植物病
害に対して防除効果を示すが、特に藻菌類によって惹起
される各種作物の疫病およびべと病に有効である。主な
防除対象病害としてはジャガイモ疫病、トマト疫病、タ
バコ疫病、イチゴ疫病、アズキ茎疫病、ブドウべと病、
キュウリべと病、ホップべと病、シュンギクべと病、あ
るいはアファノミセス属菌、ピシウム属菌等による各種
作物苗立枯病が挙げられる。The above-mentioned general formula (VI
The pyrazole derivative represented by I) has a controlling effect against a wide range of plant diseases, but is particularly effective against the plague and downy mildew of various crops caused by algae. Major diseases to be controlled are potato disease, tomato disease, tobacco disease, strawberry disease, adzuki bean disease, grape downy mildew,
Examples thereof include cucumber downy mildew, hop downy mildew, syungyi downy mildew, and various crop seedling blight caused by Aphanomyces spp, Pycium spp, and the like.
以下合成例により本発明に係るピラゾール−４−カル
ボン酸類の製造法を具体的に説明する。The production method of the pyrazole-4-carboxylic acids according to the present invention will be specifically described below with reference to synthetic examples.
合成例１−（Ａ）−法 1,3−ジメチルピラゾール−４−カルボン酸の合成 ２−エトキシメチレンアセト酢酸エステル18.6g（0.1
モル）とエタノール47mlの混合物を氷浴にて５℃に冷却
し、撹拌下メチルヒドラジン6.9g（0.15モル）を滴下し
た。滴下後反応液を加温し、リフラックス下４〜５時間
撹拌した。反応終了後室温まで冷却し、水230mlを加
え、塩析後三度酢酸エチルで抽出した。酢酸エチル層を
合わせ、飽和食塩水で洗浄した後、硫酸ナトリウムで乾
燥した。酢酸エチル層を減圧下に濃縮し粗エステル16.7
gを得た。水酸化ナトリウム16.7gと水33mlの混合物に撹
拌下、室温で粗エステル16.7gを加え、100〜110℃で３
〜４時間撹拌した。反応終了後室温迄冷却し、水42mlを
加えた。反応液を冷却しながら、濃塩酸を加えてpH4〜
５とし、析出した結晶を濾取し乾燥した後、水から再結
晶して所望の1,3−ジメチルピラゾール−４−カルボン
酸9.8gを得た。収率70.0％ m.p.190〜190.5℃ δ▲CDCL TMS▼（ppm）:2.49（3H,s）,3.88（3H,s）,7.8
6（1H,s）,10.64〜11.24（1H,br s） 元素分析値（％） Ｃ Ｈ Ｎ Calc 51.42 5.7519.99 Found 51.42 5.7620.01 合成例２−（Ｂ）法 １−（γ−クロロアリル）−３−メチルピラゾール−
４−カルボン酸の合成 金属ナトリウム0.75gおよびエタノール30mlより調整
したナトリウムアルコラートに３−メチルピラゾール−
４−カルボン酸エチル5.0gを加え、均一になったところ
へ1,3−ジクロロプロペン3.6gを加え、２時間加熱還流
した。反応終了後、反応物を水に排出し、酢酸エチルで
抽出し、シリカゲルカラムクロマトグラフィーにより精
製した。Synthesis Example 1- (A) -Method Synthesis of 1,3-dimethylpyrazole-4-carboxylic acid 2-ethoxymethylene acetoacetic acid ester 18.6 g (0.1
Mol) and 47 ml of ethanol were cooled to 5 ° C. in an ice bath, and 6.9 g (0.15 mol) of methylhydrazine was added dropwise with stirring. After the dropping, the reaction solution was heated and stirred under reflux for 4 to 5 hours. After completion of the reaction, the mixture was cooled to room temperature, added with 230 ml of water, salted out and extracted with ethyl acetate three times. The ethyl acetate layers were combined, washed with saturated brine, and dried over sodium sulfate. The ethyl acetate layer was concentrated under reduced pressure to give crude ester 16.7
got g. To a mixture of sodium hydroxide (16.7 g) and water (33 ml) was added the crude ester (16.7 g) at room temperature with stirring, and the mixture was mixed at 100-110 ° C for 3
Stir for ~ 4 hours. After completion of the reaction, the mixture was cooled to room temperature and 42 ml of water was added. While cooling the reaction mixture, add concentrated hydrochloric acid to add pH 4 to
5, the precipitated crystal was collected by filtration, dried and recrystallized from water to obtain 9.8 g of the desired 1,3-dimethylpyrazole-4-carboxylic acid. Yield 70.0% mp 190-190.5 ° C δ ▲ CDCL TMS ▼ (ppm): 2.49 (3H, s), 3.88 (3H, s), 7.8
6 (1H, s), 10.64 to 11.24 (1H, br s) Elemental analysis value (%) CHN Calc 51.42 5.7519.99 Found 51.42 5.7620.01 Synthesis example 2- (B) method 1- (γ-chloroallyl) -3-Methylpyrazole-
Synthesis of 4-carboxylic acid 3-Methylpyrazole was added to sodium alcoholate prepared from 0.75 g of metallic sodium and 30 ml of ethanol.
5.0 g of ethyl 4-carboxylate was added, and when it became uniform, 3.6 g of 1,3-dichloropropene was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction product was discharged into water, extracted with ethyl acetate, and purified by silica gel column chromatography.
ヘキサン−酢酸エチル系により溶出し、１−（γ−クロ
ロアリル）−３−メチルピラゾール−４−カルボン酸エ
チルＺ体2.5g（34％）、Ｅ体1.5g（20％）を得た。Ｚ体
2.5gをエタノール25ml、水酸化ナトリウム2.5gと水25ml
の混合物とともに４時間加熱撹拌した。反応終了後室温
まで冷却し、反応液を冷却しながら、濃塩酸を加えてpH
4〜５とし、析出した結晶を濾取し乾燥した後、水より
再結晶して所望の１−（γ−クロロアリル）−３−メチ
ルピラゾール−４−カルボン酸Ｚ体0.3gを得た。収率14
％、m.p.96〜100℃Ｅ体についても上記と同様の操作を
行い、目的物0.34gを得た。収率30％、m.p.152〜156℃ 以下同様にして、本発明に用いる他のピラゾール−４
−カルボン酸も合成した。Elution with a hexane-ethyl acetate system gave ethyl 1- (γ-chloroallyl) -3-methylpyrazole-4-carboxylate Z form 2.5 g (34%) and E form 1.5 g (20%). Z body
2.5 g ethanol 25 ml, sodium hydroxide 2.5 g and water 25 ml
The mixture was heated with stirring for 4 hours. After the reaction is complete, cool to room temperature and add concentrated hydrochloric acid while cooling the reaction mixture to pH.
The crystals were set to 4 to 5, and the precipitated crystals were collected by filtration, dried, and recrystallized from water to obtain 0.3 g of the desired 1- (γ-chloroallyl) -3-methylpyrazole-4-carboxylic acid Z-form. Yield 14
%, Mp 96 to 100 ° C. E body was subjected to the same operation as above to obtain 0.34 g of the desired product. Yield 30%, mp 152-156 ° C.
-Carboxylic acid was also synthesized.
上記の方法で得られるピラゾール−４−カルボン酸類
の代表例を表−１に物性値とともに示す。Representative examples of pyrazole-4-carboxylic acids obtained by the above method are shown in Table 1 together with their physical properties.
次に本発明化合物より誘導される一般式（VII）で表
されるピラゾール誘導体について参考例を挙げて具体的
に説明する。 Next, the pyrazole derivative represented by the general formula (VII) derived from the compound of the present invention will be specifically described with reference to reference examples.
参考例１ ２−（１−ｎ−ブチル−３−メチルピラゾール−４−
イルカルボニルアミノ）−４−メチル−３−ペンテンニ
トリルの合成（化合物番号−34） 塩化アンモニウム2.8g、シアン化ナトリウム1.7gを水
17mlに溶解し、これにエチルエーテル6ml、28％アンモ
ニア水3mlを加えた。氷浴にて５℃に冷却し、撹拌下に
３−メチル−２−ブテナール2.5gを滴下し、さらに同温
度で24時間撹拌した。反応終了後、エーテル層を分液
し、水層を三度エーテル抽出した後エーテル層を合わ
せ、硫酸ナトリウムで乾燥した。エーテル層を減圧下に
濃縮し、残渣にエチルエーテル20mlを加え０〜５℃に冷
却した。次いでトリエチルアミン1.1gを加えた。この中
に１−ｎ−ブチル−３−メチルピラゾール−４−カルボ
ン酸クロリド2.0gを含むエチルエーテル20mlを室温で、
撹拌下に徐々に加えた。滴下後さらに30分同温度で撹拌
を続けた後、反応液を水洗した。エーテル層を分液し、
水洗、硫酸ナトリウムで乾燥した後、エーテルを減圧下
で留去した。残渣をシリカゲルカラムクロマトグラフィ
ーにより精製した。クロロホルム−酢酸エチル系より溶
出し、所望の２−（１−ｎ−ブチル−３−メチルピラゾ
ール−４−イルカルボニルアミノ）−４−メチル−３−
ペンテンニトリル1.7gを得た。Reference Example 1 2- (1-n-butyl-3-methylpyrazole-4-
Synthesis of (ylcarbonylamino) -4-methyl-3-pentenenitrile (Compound No.-34) Ammonium chloride 2.8 g, sodium cyanide 1.7 g
It was dissolved in 17 ml, and 6 ml of ethyl ether and 3 ml of 28% aqueous ammonia were added thereto. The mixture was cooled to 5 ° C in an ice bath, 2.5 g of 3-methyl-2-butenal was added dropwise with stirring, and the mixture was further stirred at the same temperature for 24 hours. After completion of the reaction, the ether layer was separated, the aqueous layer was extracted with ether three times, the ether layers were combined, and dried over sodium sulfate. The ether layer was concentrated under reduced pressure, 20 ml of ethyl ether was added to the residue, and the mixture was cooled to 0-5 ° C. Then 1.1 g of triethylamine was added. 20 ml of ethyl ether containing 2.0 g of 1-n-butyl-3-methylpyrazole-4-carboxylic acid chloride in this, at room temperature,
It was added slowly with stirring. After the dropwise addition, stirring was continued for 30 minutes at the same temperature, and then the reaction solution was washed with water. Separate the ether layer,
After washing with water and drying over sodium sulfate, ether was distilled off under reduced pressure. The residue was purified by silica gel column chromatography. Elute from chloroform-ethyl acetate system to give the desired 2- (1-n-butyl-3-methylpyrazol-4-ylcarbonylamino) -4-methyl-3-
1.7 g of pentenenitrile was obtained.
収率62.0％ 本発明化合物より誘導される一般式（VII）で表され
るその他のピラゾール誘導体も参考例１の方法に準じて
合成できる。それらの代表例を表−２に示す。Yield 62.0% Other pyrazole derivatives represented by the general formula (VII) derived from the compound of the present invention can also be synthesized according to the method of Reference Example 1. Typical examples of them are shown in Table-2.
次に本発明化合物より誘導される一般式（VII）で表
されるピラゾール誘導体の農園芸用殺菌剤としての効力
を試験例によって説明する。製剤は以下のように調製し
て用いた。有効成分化合物は前記表−１の化合物番号で
示す。「部」は「重量部」を表わす。 Next, the efficacy of the pyrazole derivative represented by the general formula (VII) derived from the compound of the present invention as an agricultural and horticultural fungicide will be described with reference to Test Examples. The formulation was prepared and used as follows. The active ingredient compounds are shown by the compound numbers in Table 1 above. "Part" represents "part by weight".
製剤例 水和剤 化合物（１）:50部、リグニンスルホン酸ナトリウム:
10部、アルキルナフタレンスルホン酸ナトリウム:5部、
ホワイトカーボン:10部およびケイソウ土:25部を混合粉
砕し、水和剤100部を得た。Formulation example Wettable powder Compound (1): 50 parts, sodium lignin sulfonate:
10 parts, sodium alkylnaphthalene sulfonate: 5 parts,
White carbon: 10 parts and diatomaceous earth: 25 parts were mixed and ground to obtain 100 parts of a wettable powder.
試験例 ジャガイモ疫病防除試験（予防効果） 試験例において以下の化合物を対象として用いた。Test example Potato epidemic disease control test (preventive effect) The following compounds were used in the test examples.
対象化合物 A:2−ベンゾイルアミノプロピオノニトリル B:4−（2,4−ジクロロベンゾイル）−５−ベンゾイル
メトキシ−1,3−ジメチルピラゾール〔ピラゾキシン〕 C:ジンクエチレンビス（ジチオカーバメート）〔ジネ
ブ〕 D:テトラクロロイソフタロニトリル〔TPN〕 対象化合物Ａは ユスタス リービッヒ アンナーレ
ン デル ヘミー（Justus Liebigs Ann.Chem.）,1972,
764,69〜93に記載の化合物であり、Ｂは水田用除草剤と
して市販の化合物。ＣおよびＤはジャガイモ疫病、キュ
ウリべと病等の防除剤として市販の薬剤。Target compound A: 2-benzoylaminopropiononitrile B: 4- (2,4-dichlorobenzoyl) -5-benzoylmethoxy-1,3-dimethylpyrazole [pyrazoxin] C: zinc ethylene bis (dithiocarbamate) [dineb] D: Tetrachloroisophthalonitrile [TPN] Target compound A is Justus Liebigs Ann.Chem., 1972,
764, 69 to 93, wherein B is a commercially available compound as a herbicide for paddy fields. C and D are commercially available agents for controlling potato epidemics and cucumber downy mildew.
温室内でポットに育成したジャガイモ（品種：男爵、
草丈25cm程度）に所定濃度の薬剤（供試化合物を前記製
剤例に準じて水和剤を調製し、これを水で所定濃度に希
釈したもの）をスプレーガン（1.0Kg/cm2）を使用して
３鉢当り50ml散布し風乾した。予めジャガイモ切片上に
て７日間培養したジャガイモ疫病菌より遊走子浮遊液を
調製した。この浮遊液を薬剤散布したジャガイモ植物体
上に噴霧接種し、被検植物を17〜19℃、湿度95％以上で
６日間保った後、病斑の形成程度を調査した。Potatoes grown in pots in the greenhouse (variety: Baron,
Using a spray gun (1.0Kg / cm 2 ) of a drug with a specified concentration (about 25 cm in plant height) (a wettable powder was prepared from the test compound according to the above formulation example and diluted with water to a specified concentration). Then, 50 ml was sprayed on 3 pots and air-dried. A zoospore suspension was prepared from the Phytophthora infestans cultivated on potato slices for 7 days in advance. This suspension was spray-inoculated onto a potato plant sprayed with a chemical, and the test plant was kept at 17 to 19 ° C and a humidity of 95% or more for 6 days, and then the degree of lesion formation was investigated.
各葉ごとに病斑面積割合を観察評価し発病度指数を求
め、それぞれの区について次式により罹病度を求めた。The lesion area ratio was observed and evaluated for each leaf to determine the disease degree index, and the disease degree was calculated for each plot by the following formula.
なお、評価基準は次のとうりである。 The evaluation criteria are as follows.
発病程度指数0:病斑面積割合 ０％ 〃 1: 〃 １〜５％ 〃 2: 〃 ６〜25％ 〃 3: 〃 26〜50％ 〃 4: 〃 51％以上 n0 発病程度指数０の葉数 n1 〃 １ 〃 n2 〃 ２ 〃 n3 〃 ３ 〃 n4 〃 ４ 〃 Ｎ＝n0＋n1＋n2＋n3＋n4 結果を表−３に示した。Disease severity index 0: Lesion area ratio 0% 〃 1: 〃 1-5% 〃 2: 〃 6-25% 〃 3: 〃 26-50% 〃 4: 〃 51% or more n 0 Disease severity index 0 leaves Number n 1 〃 1 〃 n 2 〃 2 〃 n 3 〃 3 〃 n 4 〃 4 〃 N = n 0 + n 1 + n 2 + n 3 + n 4 The results are shown in Table-3.
〔発明の効果〕 本発明に係る新規なピラゾール−４−カルボン酸類お
よびその製造法は疫病、べと病用殺菌剤として優れた性
質を有するピラゾール誘導体の製造における重要な中間
体を提供するものであり、農産業上有用である。 [Effects of the Invention] The novel pyrazole-4-carboxylic acids and the method for producing the same according to the present invention provide important intermediates in the production of pyrazole derivatives having excellent properties as fungicides for plague and downy mildew. Yes, it is useful in the agricultural industry.
───────────────────────────────────────────────────── フロントページの続き 審査官 塚中 直子 (56)参考文献 特公 昭34−5674（ＪＰ，Ｂ１) 米国特許4245106（ＵＳ，Ａ) Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔ. （７），479〜480（1970) Ｃａｎ．Ｊ．Ｃｈｅｍ．，64（11）, 2211〜2219（1986) ─────────────────────────────────────────────────── --Continuing the Front Page Examiner Naoko Tsukanaka (56) References Japanese Patent Publication No. 345674 (JP, B1) US Pat. No. 4245106 (US, A) Tetrahedron Lett. (7), 479-480 (1970) Can ． J. Chem. , 64 (11), 2211 ~ 2219 (1986)
Claims (3)
キル基、アリル基、ハロアリル基またはメチルカーバモ
イル基を示し、R2は水素原子、炭素数１〜３のアルキル
基またはフルオロアルキル基を示す。但し、R1およびR2
が共にメチル基である場合を除く） で示されるピラゾール−４−カルボン酸誘導体。1. A general formula (I) (In the formula, R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and R 2 is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or fluoroalkyl. Group, provided that R 1 and R 2
Except when both are methyl groups).
はフルオロアルキル基を示し、Ｒは低級アルキル基を示
す） で示されるエトキシメチレンアシル酢酸エステル類を反
応させ、一般式（IV） （式中、R1、R2およびＲは前記の意味を示す） で示されるピラゾール−４−カルボン酸エステル類とし
た後、水酸化アルカリで加水分解することを特徴とする
一般式（Ｉ） （式中、R1およびR2は前記の意味を示す） で表されるピラゾール−４−カルボン酸誘導体の製造方
法。2. A hydrazine derivative represented by the general formula (II) R 1 -NHNH 2 (II) (wherein R 1 represents an alkyl group having 1 to 4 carbon atoms) and the general formula (III) (Wherein R 2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or a fluoroalkyl group, and R represents a lower alkyl group), and ethoxymethylene acyl acetic acid ester represented by the formula: ) (Wherein R 1 , R 2 and R have the above-mentioned meanings), and then the resulting pyrazole-4-carboxylic acid ester is hydrolyzed with an alkali hydroxide to give a general formula (I). (In the formula, R 1 and R 2 have the above-mentioned meanings) A method for producing a pyrazole-4-carboxylic acid derivative represented by the following formula.
はフルオロアルキル基を示し、Ｒは低級アルキル基を示
す） で示されるエトキシメチレンアシル酢酸エステル類と抱
水ヒドラジンと反応させ、一般式（Ｖ） （式中、R2およびＲは前記の意味を示す） で示される１（２）−Ｈ−ピラゾール−４−カルボン酸
エステル類とし、塩基の存在下に一般式（VI） R1X （VI） （式中、R1は炭素数１〜８のアルキル基、フルオロアル
キル基、アリル基、ハロアリル基またはメチルカルバモ
イル基を示し、Ｘはハロゲン原子を示す） で示されるハロゲン化物を反応させて一般式（IV） （式中、R1、R2およびＲは前記の意味を示す） で示されるピラゾール−４−カルボン酸エステル類とし
た後、水酸化アルカリで加水分解することを特徴とする
ピラゾール−４−カルボン酸誘導体の製造方法。3. General formula (III) (In the formula, R 2 represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or a fluoroalkyl group, and R represents a lower alkyl group), and ethoxymethylene acyl acetic acid ester represented by General formula (V) (In the formula, R 2 and R have the above-mentioned meanings) 1 (2) -H-pyrazole-4-carboxylic acid ester represented by the formula (VI) R 1 X (VI (In the formula, R 1 represents an alkyl group having 1 to 8 carbon atoms, a fluoroalkyl group, an allyl group, a haloallyl group or a methylcarbamoyl group, and X represents a halogen atom.) Formula (IV) (In the formula, R 1 , R 2 and R have the above-mentioned meanings.) A pyrazole-4-carboxylic acid ester represented by Method for producing acid derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62266612A JPH0822853B2 (en) | 1987-10-23 | 1987-10-23 | Pyrazole-4-carboxylic acids and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62266612A JPH0822853B2 (en) | 1987-10-23 | 1987-10-23 | Pyrazole-4-carboxylic acids and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01113371A JPH01113371A (en) | 1989-05-02 |
| JPH0822853B2 true JPH0822853B2 (en) | 1996-03-06 |
Family
ID=17433236
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62266612A Expired - Fee Related JPH0822853B2 (en) | 1987-10-23 | 1987-10-23 | Pyrazole-4-carboxylic acids and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0822853B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9156771B2 (en) | 2010-07-13 | 2015-10-13 | Lonza Ltd | Process for the preparation of enolate salts of 4-fluoro-2-hydroxymethylene-3 oxo-butyrates |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3934924C2 (en) * | 1989-10-20 | 1994-01-27 | Huels Chemische Werke Ag | Process for the preparation of 4-alkoxycarbonyl-3-chloromethyl-2H-pyrazoles |
| WO2006090778A1 (en) | 2005-02-25 | 2006-08-31 | Sagami Chemical Research Center | Method for producing 1-substituted-3-fluoroalkyl pyrazole-4-carboxylate |
| KR20110004891A (en) | 2008-05-02 | 2011-01-14 | 바스프 에스이 | Process for preparing 2-(aminomethylidene)-4,4-difluoro-3-oxobutyric esters |
| CN102015653B (en) | 2008-05-02 | 2013-09-11 | 巴斯夫欧洲公司 | Method for the production of halogen-substituted 2-(aminomethylidene)-3- oxobutyric acid esters |
| CA2725446A1 (en) | 2008-05-05 | 2009-11-12 | Basf Se | Method for preparing 1,3,4-substituted pyrazol compounds |
| US8344157B2 (en) | 2008-07-21 | 2013-01-01 | Basf Se | Process for preparing 1,3-disubstituted pyrazolecarboxylic esters |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4245106A (en) | 1979-07-05 | 1981-01-13 | Monsanto Company | Process for the preparation of 1-alkyl-3-aryl-4-pyrazolecarboxylates |
-
1987
- 1987-10-23 JP JP62266612A patent/JPH0822853B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4245106A (en) | 1979-07-05 | 1981-01-13 | Monsanto Company | Process for the preparation of 1-alkyl-3-aryl-4-pyrazolecarboxylates |
Non-Patent Citations (2)
| Title |
|---|
| Ｃａｎ．Ｊ．Ｃｈｅｍ．，６４（１１），２２１１〜２２１９（１９８６） |
| ＴｅｔｒａｈｅｄｒｏｎＬｅｔｔ．（７），４７９〜４８０（１９７０） |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9156771B2 (en) | 2010-07-13 | 2015-10-13 | Lonza Ltd | Process for the preparation of enolate salts of 4-fluoro-2-hydroxymethylene-3 oxo-butyrates |
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| Publication number | Publication date |
|---|---|
| JPH01113371A (en) | 1989-05-02 |
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