JPH0680643A - Production of 4-alkoxycarbonyl-5-amino-1-methylpyrazole - Google Patents
Production of 4-alkoxycarbonyl-5-amino-1-methylpyrazoleInfo
- Publication number
- JPH0680643A JPH0680643A JP23361992A JP23361992A JPH0680643A JP H0680643 A JPH0680643 A JP H0680643A JP 23361992 A JP23361992 A JP 23361992A JP 23361992 A JP23361992 A JP 23361992A JP H0680643 A JPH0680643 A JP H0680643A
- Authority
- JP
- Japan
- Prior art keywords
- methylhydrazine
- amino
- alkoxycarbonyl
- methylpyrazole
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医農薬中間体として有
用で、特に農薬除草剤の出発原料として用いられる４−
アルコキシカルボニル−５−アミノピラゾール類の製法
に関するものである。BACKGROUND OF THE INVENTION The present invention is useful as an intermediate for medicines and agricultural chemicals, and particularly used as a starting material for agricultural chemical herbicides.
The present invention relates to a method for producing alkoxycarbonyl-5-aminopyrazoles.
【０００２】[0002]
【従来の技術及び発明が解決しようとする課題】従来、
４−アルコキシカルボニル−５−アミノ−１−メチルピ
ラゾールはヘルベチカ・キミカ・アクタ（Ｈｅｌｖ．Ｃ
ｈｉｍ．Ａｃｔａ．），ピー・シュミット等（Ｐ．Ｓｃ
ｈｍｉｄｔ ｅｔ ａｌ．），第４２巻，３４９〜３５
９頁（１９５９），米国特許４１２４７６４等に記載の
如く、無水エタノールにエトキシメチレンシアノ酢酸エ
チルエステルを溶かし、室温で高純度メチルヒドラジン
を滴下後、加温して環化している。しかるに従来法で使
用しているメチルヒドラジンの８０〜９８％の高濃度市
販品は高価であり、かつ引火の危険性が高いため、輸
送、貯蔵、反応時の取扱いに難点がある。2. Description of the Related Art Conventionally, the problems to be solved by the invention
4-Alkoxycarbonyl-5-amino-1-methylpyrazole is commercially available from Helvetica Kimika Acta (Helv.
him. Acta. ), P. Schmidt, etc. (P. Sc
hmidt et al. ), Vol. 42, 349-35
As described on page 9 (1959), U.S. Pat. No. 4,124,764 and the like, ethoxymethylene cyanoacetic acid ethyl ester is dissolved in absolute ethanol, and high-purity methylhydrazine is added dropwise at room temperature, followed by heating for cyclization. However, a commercial product of methylhydrazine having a high concentration of 80 to 98%, which is used in the conventional method, is expensive and has a high risk of catching fire, so that it is difficult to handle during transportation, storage and reaction.
【０００３】一方、安全性の高い３５％メチルヒドラジ
ン水溶液を従来法に適用した場合、収率が低く、異性体
の４−アルコキシカルボニル−３−アミノ−１−メチル
ピラゾール（以下３−アミノ体と略す）の生成が多く、
晶析、精製しないと次行程に使用することは困難であ
る。このため安全性の高い３５％メチルヒドラジン水溶
液を使用する高収率で高品質な４−Ｃ1-4 アルコキシカ
ルボニル−５−アミノ−１−メチルピラゾールの製法が
望まれている。On the other hand, when a highly safe 35% aqueous solution of methylhydrazine was applied to the conventional method, the yield was low and the isomer 4-alkoxycarbonyl-3-amino-1-methylpyrazole (hereinafter referred to as 3-amino compound) was obtained. Abbreviated) is often generated,
It is difficult to use in the next process without crystallization and purification. Therefore, there is a demand for a high-yield and high-quality production method of 4-C 1-4 alkoxycarbonyl-5-amino-1-methylpyrazole using a highly safe 35% methylhydrazine aqueous solution.
【０００４】[0004]
【課題を解決するための手段】本発明者らは鋭意研究を
重ねた結果、Ｃ1-4 アルコキシメチレンシアノ酢酸Ｃ
1-4 アルキルエステルを芳香族溶媒中で、３０〜４０％
メチルヒドラジン水溶液と反応させることにより、４−
Ｃ1-4 アルコキシカルボニル−５−アミノ−１−メチル
ピラゾールを高収率で得ることを見い出し、本発明を完
成した。[Means for Solving the Problems] The present inventors
As a result of overlapping, C1-4Alkoxymethylene cyanoacetic acid C
1-430-40% of alkyl ester in aromatic solvent
By reacting with an aqueous solution of methylhydrazine, 4-
C1-4Alkoxycarbonyl-5-amino-1-methyl
The present invention was completed by finding that pyrazole was obtained in high yield.
I made it.
【０００５】[0005]
【化１】 [Chemical 1]
【０００６】（式中、Ｒ1 及びＲ2 はそれぞれ独立し
て、Ｃ1-4 アルキル基を表す。）この反応を液体クロマ
トグラフィーで解析すると主反応は次の如く、２段反応
で進行し、途中不安定な中間体 [Ａ] が生成した後環化
して目的物を得ている。一方副生成物の３−アミノ体は
中間体 [Ｂ] 、或いは [Ｃ] を経由しているものと推定
される。(In the formula, R 1 and R 2 each independently represent a C 1-4 alkyl group.) When this reaction is analyzed by liquid chromatography, the main reaction proceeds in a two-step reaction as follows. Then, an unstable intermediate [A] is produced and then cyclized to obtain the desired product. On the other hand, the 3-amino compound as a by-product is presumed to pass through the intermediate [B] or [C].
【０００７】[0007]
【化２】 [Chemical 2]
【０００８】高濃度メチルヒドラジンを使用する場合は
アルコール類、芳香族溶媒何れの場合もａ行程の反応が
早く３−アミノ体の生成は少ない（従来法）。しかるに
３５％メチルヒドラジン水溶液を使用するとき、アルコ
ール類のような水溶性溶媒では、水の存在でａ行程の中
間体生成が遅く、相対的にｂ行程の中間体が生成し、加
温により異性体の３−アミノ体の生成が多くなる。When high-concentration methylhydrazine is used, the reaction in the step a is fast and the 3-amino compound is little produced in both alcohols and aromatic solvents (conventional method). However, when a 35% aqueous solution of methylhydrazine is used, in a water-soluble solvent such as alcohols, the presence of water slows the formation of the intermediate in the a step, and the intermediate in the b step is relatively formed. Increased production of the 3-amino form of the body.
【０００９】溶媒を芳香族溶媒に変えると３５％メチル
ヒドラジン水溶液の場合、２層溶液反応となり、主反応
のａ行程を経由する反応が強くなり、４−Ｃ1-4 アルコ
キシカルボニル−５−アミノ−１−メチルピラゾールの
生成収率が高くなる。芳香族溶媒としては、ベンゼン、
キシレン、クロルベンゼン等の水に難溶性溶媒があげら
れる。When the solvent is changed to an aromatic solvent, in the case of a 35% methylhydrazine aqueous solution, a two-layer solution reaction occurs, and the reaction via the a step of the main reaction becomes strong, resulting in 4-C 1-4 alkoxycarbonyl-5-amino. The production yield of -1-methylpyrazole increases. As the aromatic solvent, benzene,
A poorly water-soluble solvent such as xylene or chlorobenzene can be used.
【００１０】メチルヒドラジンの量は、Ｃ1-4 アルコキ
シメチレンシアノ酢酸Ｃ1-4 アルキルエステルに対して
１．０〜１．３モル倍が適量である。メチルヒドラジン
の使用量が当量以下の場合はＣ行程の中間体の生成を経
ることが推定され、３−アミノ体の生成が増加する。一
方、メチルヒドラジンの使用量が過剰の場合は、反応後
の廃水処理に支障をきたすことになる。An appropriate amount of methylhydrazine is 1.0 to 1.3 times the molar amount of C 1-4 alkoxymethylene cyanoacetic acid C 1-4 alkyl ester. When the amount of methylhydrazine used is not more than the equivalent amount, it is estimated that the intermediate in the C stage is produced, and the production of the 3-amino compound is increased. On the other hand, if the amount of methylhydrazine used is excessive, it will hinder the treatment of wastewater after the reaction.
【００１１】反応時、生成アルカノールを除去するため
に徐々に加温するが、通常４０〜９０℃まで加温し、好
ましくは５０〜８０℃まで加温する。反応時に生成アル
カノールを除去するために徐々に減圧するが、通常１５
０〜３ｍｍＨｇまで減圧し、好ましくは５０〜４ｍｍＨ
ｇまで減圧する。更に具体的にあげれば、トルエン、ベ
ンゼン、キシレン又はクロルベンゼン等の水に難溶性の
芳香族溶媒にＣ1-4 アルコキシメチレンシアノ酢酸Ｃ
1-4 アルキルエステルを溶解した後、冷却し、ゆるいス
ラリーとし、３５％メチルヒドラジン水溶液を室温以下
で滴下する。次いで徐々に加温して５０〜８０℃で減圧
度を５０〜４ｍｍＨｇに上げ、水及び生成アルカノール
を留去することにより反応を完結する。During the reaction, the temperature is gradually increased in order to remove the alkanol formed, but the temperature is usually raised to 40 to 90 ° C, preferably 50 to 80 ° C. The pressure is gradually reduced to remove the alkanol formed during the reaction, but usually 15
Reduce the pressure to 0 to 3 mmHg, preferably 50 to 4 mmH
Depressurize to g. More specifically, a water-insoluble aromatic solvent such as toluene, benzene, xylene or chlorobenzene is added to C 1-4 alkoxymethylene cyanoacetic acid C
After the 1-4 alkyl ester is dissolved, it is cooled to form a loose slurry, and a 35% methylhydrazine aqueous solution is added dropwise at room temperature or below. Next, the temperature is gradually increased to 50 to 80 ° C. and the degree of reduced pressure is increased to 50 to 4 mmHg, and the reaction is completed by distilling off water and the produced alkanol.
【００１２】次に具体的な実施例を示すが、この範囲に
限定されるものでない。Next, specific examples will be shown, but the invention is not limited to this range.
【００１３】[0013]
〔実施例１〕２リットルの反応フラスコにトルエン４０
０ｇ，９８％エトキシメチレンシアノ酢酸エチルエステ
ル１７２．７ｇ（１．０モル）を仕込み、溶解後１０℃
に冷却した。次にフラスコ内を窒素ガスで置換し、３５
％メチルヒドラジン水溶液１４４．８ｇ（１．１０モ
ル）を２時間かけて滴下した。滴下後１時間かけて５０
℃まで加温し、５０〜６０℃で５時間徐々に減圧し（〜
１０ｍｍＨｇ）、エタノール及び水を留去し、更に温度
及び減圧度を上げ、最終的に７０〜７５℃、４ｍｍＨｇ
で２時間反応を行なった。反応液を分析すると、収率９
７％で目的物が検出された。窒素でフラスコ内を減圧ブ
レークし、トルエン６００mlを加えた後、６０〜６５℃
に保ちながら水２０ｇで洗浄した。トルエンを留去して
純度９６％の５−アミノ−４−エトキシカルボニル−１
−メチルピラゾール１６０ｇを得た。収率９１％、融点
１０２℃（トルエン再結晶）。反応液中の３−アミノ体
はトレース（０．１％以下）であった。Example 1 Toluene 40 was added to a 2 liter reaction flask.
Charge 0 g, 98% ethoxymethylene cyanoacetic acid ethyl ester 172.7 g (1.0 mol), and after dissolution, 10 ° C.
Cooled to. Then, the inside of the flask was replaced with nitrogen gas,
% Aqueous solution of methylhydrazine (144.8 g, 1.10 mol) was added dropwise over 2 hours. 50 hours after dropping
Warm to 50 ° C and gradually reduce pressure at 50-60 ° C for 5 hours (~
10 mmHg), ethanol and water are distilled off, the temperature and the degree of reduced pressure are further raised, and finally 70 to 75 ° C., 4 mmHg
The reaction was carried out for 2 hours. The reaction solution was analyzed and the yield was 9
The target substance was detected in 7%. After decompressing the inside of the flask with nitrogen and adding 600 ml of toluene, 60-65 ° C
It was washed with 20 g of water while maintaining the above. Toluene was distilled off to give 96% pure 5-amino-4-ethoxycarbonyl-1.
160 g of methylpyrazole were obtained. Yield 91%, melting point 102 ° C (toluene recrystallization). The 3-amino compound in the reaction solution was a trace (0.1% or less).
【００１４】〔実施例２〕実施例１と同様な方法で３５
％メチルヒドラジン水溶液を滴下後加温し、５０〜５３
℃に保持しながら徐々に減圧度を１３０ｍｍＨｇにして
エタノール及び水を留去した。２時間後反応生成物を分
析すると収率９５．０％であり、３−アミノ体の生成は
トレースであった。[Embodiment 2] In the same manner as in Embodiment 1, 35
% Methylhydrazine aqueous solution was added dropwise and then heated to 50-53.
While maintaining the temperature at 0 ° C., the degree of vacuum was gradually adjusted to 130 mmHg, and ethanol and water were distilled off. When the reaction product was analyzed after 2 hours, the yield was 95.0%, and the formation of the 3-amino compound was trace.
【００１５】〔参考例１〕実施例１と同様な方法で、ト
ルエンをエタノールに変えて実施し、３５％メチルヒド
ラジン水溶液を滴下した。５５〜７５℃で２．５時間加
温後、７６〜９１℃で１．５時間エタノールを留去し
た。生成反応物を分析すると目的物の収率は８４．５％
であり、３−アミノ体は４．７％生成した。Reference Example 1 In the same manner as in Example 1, except that toluene was changed to ethanol, the operation was carried out, and a 35% aqueous solution of methylhydrazine was added dropwise. After heating at 55 to 75 ° C for 2.5 hours, ethanol was distilled off at 76 to 91 ° C for 1.5 hours. When the reaction product is analyzed, the yield of the desired product is 84.5%.
And the 3-amino compound was produced at 4.7%.
【００１６】[0016]
【発明の効果】医農薬中間体として有用で、特に農薬除
草剤の出発原料として用いられる４−Ｃ1-4 アルコキシ
カルボニル−５−アミノ−１−メチルピラゾールを安全
に、収率よく製造できる。INDUSTRIAL APPLICABILITY 4-C 1-4 alkoxycarbonyl-5-amino-1-methylpyrazole, which is useful as an intermediate for medicines and agricultural chemicals and is particularly used as a starting material for agricultural chemical herbicides, can be produced safely and in high yield.
Claims (4)
1-4 アルキルエステルを芳香族溶媒中で、３０〜４０％
メチルヒドラジンの水溶液と反応させることを特徴とす
る４−Ｃ1-4 アルコキシカルボニル−５−アミノ−１−
メチルピラゾールの製法。1. A C 1-4 alkoxymethylene cyanoacetic acid C
1-4 alkyl ester in aromatic solvent, 30-40%
4-C 1-4 alkoxycarbonyl-5-amino-1-characterized by reacting with an aqueous solution of methylhydrazine
Manufacturing method of methylpyrazole.
1-4 アルキルエステルに対して、１．０〜１．３モル倍
のメチルヒドラジンを使用する請求項１の４−Ｃ1-4 ア
ルコキシカルボニル−５−アミノ−１−メチルピラゾー
ルの製法。2. A C 1-4 alkoxymethylene cyanoacetic acid C
The method for producing 4-C 1-4 alkoxycarbonyl-5-amino-1-methylpyrazole according to claim 1, wherein 1.0 to 1.3 mol of methylhydrazine is used with respect to 1-4 alkyl ester.
り、水及び生成Ｃ1-4アルカノールを除去することを特
徴とする請求項１の４−Ｃ1-4 アルコキシカルボニル−
５−アミノ−１−メチルピラゾールの製法。3. The 4-C 1-4 alkoxycarbonyl-group according to claim 1, wherein water and the produced C 1-4 alkanol are removed by gradually heating and reducing the pressure during the reaction.
A process for producing 5-amino-1-methylpyrazole.
シレン又はクロルベンゼンである請求項１の４−Ｃ1-4
アルコキシカルボニル−５−アミノ−１−メチルピラゾ
ールの製法。4. The 4-C 1-4 of claim 1, wherein the aromatic solvent is toluene, benzene, xylene or chlorobenzene.
Process for producing alkoxycarbonyl-5-amino-1-methylpyrazole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23361992A JP3489125B2 (en) | 1992-09-01 | 1992-09-01 | Method for producing 4-alkoxycarbonyl-5-amino-1-methylpyrazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23361992A JP3489125B2 (en) | 1992-09-01 | 1992-09-01 | Method for producing 4-alkoxycarbonyl-5-amino-1-methylpyrazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0680643A true JPH0680643A (en) | 1994-03-22 |
| JP3489125B2 JP3489125B2 (en) | 2004-01-19 |
Family
ID=16957889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23361992A Expired - Fee Related JP3489125B2 (en) | 1992-09-01 | 1992-09-01 | Method for producing 4-alkoxycarbonyl-5-amino-1-methylpyrazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3489125B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011201794A (en) * | 2010-03-24 | 2011-10-13 | Fujifilm Corp | Process for producing 5-aminopyrazole derivative and salt thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102603638A (en) * | 2012-02-17 | 2012-07-25 | 张学生 | Synthesis process of pyrazole amine |
-
1992
- 1992-09-01 JP JP23361992A patent/JP3489125B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011201794A (en) * | 2010-03-24 | 2011-10-13 | Fujifilm Corp | Process for producing 5-aminopyrazole derivative and salt thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3489125B2 (en) | 2004-01-19 |
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