JP2007302619A - Method for producing pyrazolinone derivative - Google Patents
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Description
本発明は、一般式（１） The present invention relates to general formula (1)
（式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4及びＲ5はそれぞれ水素原子、ハロゲン原子又はハロゲン原子で置換されていてもよいメチル基を表す。Ｒ6は水素原子又は炭素数１〜５のアルキル基を表す。） (Wherein, R 1, R 2, R 3, R 4 and R 5 are each a hydrogen atom, .R 6 is 1 hydrogen atom or a carbon atoms of a halogen atom or a halogen atom which may be substituted methyl group 5 represents an alkyl group.)
で示される化合物〔以下、ピラゾリノン化合物（１）ということがある。〕と、一般式（２） [Hereinafter, it may be called a pyrazolinone compound (1). ] And general formula (2)
（式中、Ｘは塩素原子又は臭素原子を表し、Ｙは酸素原子又は硫黄原子を表す。Ｒ7は炭素数１〜５のアルキル基、炭素数３〜５のアルケニル基又は炭素数３〜５のアルキニル基を表す。） (In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom or a sulfur atom. R 7 represents an alkyl group having 1 to 5 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, or 3 to 5 carbon atoms. Represents an alkynyl group of
で示される化合物〔以下、酸ハロゲン化物（２）ということがある。〕とを塩基存在下で反応させ、一般式（３） [Hereinafter, referred to as acid halide (2). And in the presence of a base to give a general formula (3)
（式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ5、Ｒ6、Ｒ7及びＹはそれぞれ前記と同じ意味を表す。） (Wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and Y have the same meanings as described above).
で示される化合物〔以下、ピラゾリノン誘導体（３）ということがある。〕を製造する方法に関する。ピラゾリノン誘導体（３）は、例えば、農薬の原料として有用である。 [Hereinafter, it may be referred to as a pyrazolinone derivative (3). ] About the method of manufacturing. The pyrazolinone derivative (3) is useful as a raw material for agricultural chemicals, for example.
ピラゾリノン誘導体（３）の製造方法として、例えば特開２０００−２２６３７４号公報（特許文献１）には、ピラゾリノン化合物（１）と酸ハロゲン化物（２）とを塩基存在下で反応させ、得られた反応混合物を酸処理することにより、ピラゾリノン誘導体（３）を析出させて取り出すことが開示されている。 As a method for producing a pyrazolinone derivative (3), for example, JP-A-2000-226374 (Patent Document 1) was obtained by reacting a pyrazolinone compound (1) with an acid halide (2) in the presence of a base. It is disclosed that a pyrazolinone derivative (3) is precipitated by acid treatment of the reaction mixture.
上記従来の方法では、反応の際、目的物であるピラゾリノン誘導体（３）の他に、２分子のピラゾリノン化合物（１）がカルボニル基によって繋がった構造を持つ尿素化合物が副生するが、この副生物はピラゾリノン誘導体（３）の析出物中に取り込まれ易く、品質上必ずしも満足の行くものではなかった。そこで、本発明の目的は、上記副生物の取り込みを抑制して、良好な品質でピラゾリノン誘導体（３）を製造しうる方法を提供することにある。 In the conventional method, a urea compound having a structure in which two molecules of the pyrazolinone compound (1) are connected by a carbonyl group is produced as a by-product in addition to the target pyrazolinone derivative (3) during the reaction. Living organisms are easily incorporated into the precipitate of the pyrazolinone derivative (3), and are not always satisfactory in quality. Accordingly, an object of the present invention is to provide a method capable of producing the pyrazolinone derivative (3) with good quality by suppressing the incorporation of the by-products.
本発明者らは鋭意研究を行った結果、ピラゾリノン化合物（１）と酸ハロゲン化物（２）との反応により得られた反応混合物に、酸を所定時間以上かけて加えることで、上記副生物の取り込みが抑制できることを見出し、本発明を完成するに至った。即ち、本発明は、ピラゾリノン化合物（１）と酸ハロゲン化物（２）とを塩基存在下で反応させ、得られた反応混合物に酸を３時間以上かけて加えることにより、ピラゾリノン誘導体（３）を析出させることを特徴とするピラゾリノン誘導体（３）の製造方法を提供するものである。 As a result of intensive studies, the inventors of the present invention added an acid to the reaction mixture obtained by the reaction of the pyrazolinone compound (1) and the acid halide (2) over a predetermined period of time, whereby The inventors have found that the uptake can be suppressed, and have completed the present invention. That is, in the present invention, the pyrazolinone compound (1) and the acid halide (2) are reacted in the presence of a base, and an acid is added to the obtained reaction mixture over 3 hours, whereby the pyrazolinone derivative (3) is obtained. The present invention provides a method for producing a pyrazolinone derivative (3) characterized by being precipitated.
本発明によれば、ピラゾリノン誘導体（３）を良好な品質で製造することができる。 According to the present invention, the pyrazolinone derivative (3) can be produced with good quality.
以下に本発明について詳細に説明する。ピラゾリノン化合物（１）を示す一般式（１） The present invention is described in detail below. General formula (1) showing the pyrazolinone compound (1)
（式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4及びＲ5はそれぞれ水素原子、ハロゲン原子又はハロゲン原子で置換されていてもよいメチル基を表す。Ｒ6は水素原子又は炭素数１〜５のアルキル基を表す。） (Wherein, R 1, R 2, R 3, R 4 and R 5 are each a hydrogen atom, .R 6 is 1 hydrogen atom or a carbon atoms of a halogen atom or a halogen atom which may be substituted methyl group 5 represents an alkyl group.)
において、Ｒ1、Ｒ2、Ｒ3、Ｒ4及びＲ5の少なくとも１つがハロゲン原子又はハロゲン原子で置換されたメチル基である場合、このハロゲン原子は、フッ素原子、塩素原子、臭素原子又はヨウ素原子であることができる。また、ハロゲン原子で置換されたメチル基は、モノフルオロメチル基やモノクロロメチル基の如きモノハロメチル基であってもよいし、ジフルオロメチル基やジクロロメチル基の如きジハロメチル基であってもよいし、トリフルオロメチル基やトリクロロメチル基の如きトリハロメチル基であってもよい。Ｒ6が炭素数１〜５のアルキル基である場合、このアルキル基としては、例えば、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、イソブチル基、ｔｅｒｔ−ブチル基、ｎ−ペンチル基等が挙げられる。 In this case, when at least one of R 1 , R 2 , R 3 , R 4 and R 5 is a halogen atom or a methyl group substituted by a halogen atom, the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine Can be an atom. The methyl group substituted with a halogen atom may be a monohalomethyl group such as a monofluoromethyl group or a monochloromethyl group, a dihalomethyl group such as a difluoromethyl group or a dichloromethyl group, or a trihalomethyl group. It may be a trihalomethyl group such as a fluoromethyl group or a trichloromethyl group. When R 6 is an alkyl group having 1 to 5 carbon atoms, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group, Examples thereof include a tert-butyl group and an n-pentyl group.
酸ハロゲン化物（２）を示す一般式（２） General formula (2) showing acid halide (2)
（式中、Ｘは塩素原子又は臭素原子を表し、Ｙは酸素原子又は硫黄原子を表す。Ｒ7は炭素数１〜５のアルキル基、炭素数３〜５のアルケニル基又は炭素数３〜５のアルキニル基を表す。） (In the formula, X represents a chlorine atom or a bromine atom, Y represents an oxygen atom or a sulfur atom. R 7 represents an alkyl group having 1 to 5 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, or 3 to 5 carbon atoms. Represents an alkynyl group of
において、Ｒ7が炭素数１〜５のアルキル基である場合、このアルキル基としては、例えば、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、イソブチル基、ｔｅｒｔ−ブチル基、ｎ−ペンチル基等が挙げられる。Ｒ7が炭素数３〜５のアルケニル基である場合、このアルケニル基としては、例えば、アリル基（２−プロペニル基）、メタリル基（２−メチル−２−プロペニル基）、クロチル基（２−ブテニル基）等が挙げられる。Ｒ7が炭素数３〜５のアルキニル基である場合、このアルキニル基としては、例えば、２−プロピニル基、２−ブチニル基又は３−ブチニル基等が挙げられる。 When R 7 is an alkyl group having 1 to 5 carbon atoms, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, and an isobutyl group. Group, tert-butyl group, n-pentyl group and the like. When R 7 is an alkenyl group having 3 to 5 carbon atoms, examples of the alkenyl group include an allyl group (2-propenyl group), a methallyl group (2-methyl-2-propenyl group), a crotyl group (2- Butenyl group) and the like. When R 7 is an alkynyl group having 3 to 5 carbon atoms, examples of the alkynyl group include a 2-propynyl group, a 2-butynyl group, and a 3-butynyl group.
ピラゾリノン化合物（１）と酸ハロゲン化物（２）との反応は、塩基存在下で行われる。塩基としては、例えば、水酸化リチウム、水酸化ナトリウム、水酸化カリウムのようなアルカリ金属水酸化物、水酸化マグネシウム、水酸化カルシウムのようなアルカリ土類金属水酸化物、炭酸ナトリウム、炭酸カリウムのようなアルカリ金属炭酸塩、炭酸水素ナトリウム、炭酸水素カリウムのようなアルカリ金属重炭酸塩等の無機塩基や、ピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミン等の有機塩基が挙げられる。上記無機塩基を使用する場合、水溶液として使用することもできる。好ましくはアルカリ金属水酸化物の水溶液を用いる。 The reaction between the pyrazolinone compound (1) and the acid halide (2) is carried out in the presence of a base. Examples of the base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, sodium carbonate and potassium carbonate. Examples thereof include inorganic bases such as alkali metal carbonates, alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, and organic bases such as pyridine, 4- (dimethylamino) pyridine and triethylamine. When using the said inorganic base, it can also be used as aqueous solution. Preferably, an aqueous solution of an alkali metal hydroxide is used.
反応に用いる酸ハロゲン化物（２）の使用量は、ピラゾリノン化合物（１）１モルに対して、通常０．５〜５モルであり、好ましくは０．９〜１．５モルである。反応に用いる塩基の使用量は、ピラゾリノン化合物（１）１モルに対し、通常１〜５モルであり、好ましくは１．５〜２．５モルである。 The usage-amount of the acid halide (2) used for reaction is 0.5-5 mol normally with respect to 1 mol of pyrazolinone compounds (1), Preferably it is 0.9-1.5 mol. The usage-amount of the base used for reaction is 1-5 mol normally with respect to 1 mol of pyrazolinone compounds (1), Preferably it is 1.5-2.5 mol.
反応は通常溶媒中で行われる。溶媒としては、例えば、メタノール、エタノール、プロパノールのようなアルコール、ベンゼン、トルエン、キシレン、クロロベンゼンのような芳香族炭化水素、ｎ−へキサン、ｎ−へプタンのような脂肪族炭化水素、シクロペンタン、シクロヘキサンのような脂環式炭化水素、アセトン、メチルエチルケトン、メチルイソブチルケトンのようなケトン、ジエチルエーテル、ジブチルエーテル、テトラヒドロフラン、１,４−ジオキサン、テトラヒドロピランのようなエーテル等の有機溶媒や、水が挙げられ、必要によりそれらの２種以上からなる混合溶媒を用いることもできる。また、水と有機溶媒の混合溶媒を用いる場合、この混合溶媒は均一に混じりあったものであってもよいし、不均一な２相系となっていてもよい。 The reaction is usually carried out in a solvent. Examples of the solvent include alcohols such as methanol, ethanol and propanol, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbons such as n-hexane and n-heptane, and cyclopentane. Organic solvents such as cycloaliphatic hydrocarbons such as cyclohexane, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, 1,4-dioxane and tetrahydropyran, and water If necessary, a mixed solvent composed of two or more of them can also be used. Moreover, when using the mixed solvent of water and an organic solvent, this mixed solvent may be mixed uniformly, and may be a non-uniform two-phase system.
上記溶媒の使用量は、ピラゾリノン化合物（１）１重量部に対し、通常１〜２０重量部であり、好ましくは１〜１０重量部である。 The usage-amount of the said solvent is 1-20 weight part normally with respect to 1 weight part of pyrazolinone compound (1), Preferably it is 1-10 weight part.
反応温度は通常０〜１００℃、好ましくは１０〜５０℃である。また、反応は、通常、常圧付近で行われるが、必要により加圧下又は減圧下で行われてもよい。反応方式としては、連続式、半連続式、回分式のいずれも採用することができる。 The reaction temperature is usually 0 to 100 ° C., preferably 10 to 50 ° C. In addition, the reaction is usually performed near normal pressure, but may be performed under pressure or under reduced pressure as necessary. As the reaction system, any of a continuous system, a semi-continuous system, and a batch system can be employed.
仕込み順序には特に制限はなく、ピラゾリノン化合物（１）と塩基との混合物に酸ハロゲン化物（２）を加えてもよく、酸ハロゲン化物（２）にピラゾリノン化合物（１）と塩基との混合物を加えてもよい。また、ピラゾリノン化合物（１）と塩基の混合物に酸ハロゲン化物（２）と塩基とをそれぞれ加えてもよい。 The order of preparation is not particularly limited, and the acid halide (2) may be added to the mixture of the pyrazolinone compound (1) and the base, and the mixture of the pyrazolinone compound (1) and the base may be added to the acid halide (2). May be added. Further, the acid halide (2) and the base may be added to the mixture of the pyrazolinone compound (1) and the base, respectively.
反応終了後の反応混合物に酸を加え、目的物である一般式（３） An acid is added to the reaction mixture after completion of the reaction to obtain the general formula (3) as the target product
（式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ5、Ｒ6、Ｒ7及びＹはそれぞれ前記と同じ意味を表す。） (Wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and Y have the same meanings as described above).
で示されるピラゾリノン誘導体（３）を固体として析出させる。 Is deposited as a solid.
反応混合物に加える酸としては、例えば、塩化水素や硫酸等が挙げられ、その水溶液が好ましく用いられる。酸の使用量は、ピラゾリノン化合物（１）１モルに対し、通常０．５〜５モルであり、好ましくは０．７〜１．５モルである。品質面、操作面から酸を加えた後の反応混合物のｐＨは５以上であることが好ましく、また、ピラゾリノン誘導体（３）を十分に析出させるため、酸を加えた後の反応混合物のｐＨは９以下であることが好ましい。ｐＨの調整は、酸の使用量を調整することで行うことができる。 Examples of the acid added to the reaction mixture include hydrogen chloride and sulfuric acid, and an aqueous solution thereof is preferably used. The usage-amount of an acid is 0.5-5 mol normally with respect to 1 mol of pyrazolinone compounds (1), Preferably it is 0.7-1.5 mol. The pH of the reaction mixture after addition of the acid is preferably 5 or more in terms of quality and operation, and the pH of the reaction mixture after addition of the acid is sufficient to precipitate the pyrazolinone derivative (3) sufficiently. It is preferably 9 or less. The pH can be adjusted by adjusting the amount of acid used.
また、酸を加える前の反応混合物は、ピラゾリノン誘導体（３）が溶媒に溶解したものであるのが好ましい。 Moreover, it is preferable that the reaction mixture before adding an acid is what a pyrazolinone derivative (3) melt | dissolved in the solvent.
反応混合物に酸を加える時間は、析出するピラゾリノン誘導体（３）への前記副生物の取り込みを抑えるため、３時間以上とする。一方、上限は特に限定されないが、生産性の観点から通常２０時間以下である。 The time for adding the acid to the reaction mixture is 3 hours or longer in order to suppress the incorporation of the by-product into the precipitated pyrazolinone derivative (3). On the other hand, the upper limit is not particularly limited, but is usually 20 hours or less from the viewpoint of productivity.
酸を加え、ピラゾリノン誘導体（３）を析出させた後、該析出物を含む混合物をろ過し、ろ上物を水や有機溶媒によって洗浄することにより、目的物であるピラゾリノン誘導体（３）を固体として得ることができる。 After adding an acid and precipitating the pyrazolinone derivative (3), the mixture containing the precipitate is filtered, and the filtered product is washed with water or an organic solvent, whereby the target pyrazolinone derivative (3) is solidified. Can be obtained as
かくして、ピラゾリノン誘導体（３）を、前記副生物の取り込みを抑制し、良好な品質で得ることができる。更に、必要に応じて、再結晶やカラムクロマトグラフィー等の手段により精製することも可能である。 Thus, the pyrazolinone derivative (3) can be obtained with good quality while suppressing the by-product incorporation. Furthermore, it can be purified by means such as recrystallization or column chromatography, if necessary.
以下、本発明の実施例を示すが、本発明はこれによって限定されるものではない。 Examples of the present invention will be described below, but the present invention is not limited thereto.
実施例１
還流冷却器、温度計、攪拌器、滴下ロートを備えたガラス製反応器に、３−アミノ−４−（２−メチルフェニル）−ピラゾリン−５−オン〔一般式（１）においてＲ1がメチル基、Ｒ2、Ｒ3、Ｒ4、Ｒ5及びＲ6が水素原子である化合物〕１５．００ｇ（０．０７９モル）、メタノール３０．００ｇ、水５．３９ｇ、キシレン４５．００ｇ及び２５％水酸化ナトリウム水溶液１３．３２ｇを入れ攪拌した。この混合物に１５℃にてアリルクロロチオホルメート〔一般式（２）においてＸが塩素原子、Ｙが硫黄原子、Ｒ7がアリル基である化合物〕１０．６１ｇ（０．０７８モル）とキシレン９．１０ｇの混合物、及び１０％水酸化ナトリウム溶液３１．９７ｇをそれぞれ２時間かけて滴下し、滴下終了後、同温度でさらに２時間攪拌した。その後、反応混合物に２５℃にて１０％塩酸２８．１８ｇを４時間かけて滴下し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オン〔一般式（３）においてＲ1がメチル基、Ｒ2、Ｒ3、Ｒ4、Ｒ5及びＲ6が水素原子、Ｙが硫黄原子、Ｒ7がアリル基である化合物〕を析出させた。このときのｐＨは６．５であった。これにｎ−へキサン３０．００ｇを加え１時間攪拌後、ろ過した。ろ上物をｎ−へキサン、次いでメタノール水で洗浄し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オンを１９．０５ｇ得た。これを高速液体クロマトグラフィーにより分析し、純度を絶対検量線法により算出し、原料である３−アミノ−４−（２−メチルフェニル）−ピラゾリン−５−オンに対する収率を求めた。その結果、純度９７．６％、収率８３．０％であった。また、副生物である尿素化合物の含有量を面積百分率法にて算出したところ、その含有量は０．５％であった。
Example 1
A glass reactor equipped with a reflux condenser, a thermometer, a stirrer, and a dropping funnel was charged with 3-amino-4- (2-methylphenyl) -pyrazolin-5-one [in the general formula (1), R 1 represents methyl Group wherein R 2 , R 3 , R 4 , R 5 and R 6 are hydrogen atoms] 15.00 g (0.079 mol), methanol 30.00 g, water 5.39 g, xylene 45.00 g and 25% Sodium hydroxide aqueous solution 13.32g was added and stirred. To this mixture at 15 ° C., allyl chlorothioformate [a compound in which X is a chlorine atom, Y is a sulfur atom, and R 7 is an allyl group in general formula (2)] 10.61 g (0.078 mol) and xylene 9 .10 g of the mixture and 31.97 g of 10% sodium hydroxide solution were added dropwise over 2 hours, and after completion of the addition, the mixture was further stirred at the same temperature for 2 hours. Thereafter, 28.18 g of 10% hydrochloric acid was added dropwise to the reaction mixture over 4 hours at 25 ° C., and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H— Pyrazol-3-one [compound in which R 1 is a methyl group, R 2 , R 3 , R 4 , R 5 and R 6 are hydrogen atoms, Y is a sulfur atom, and R 7 is an allyl group in general formula (3)] Was precipitated. The pH at this time was 6.5. To this was added 30.00 g of n-hexane, and the mixture was stirred for 1 hour and filtered. The filtered product was washed with n-hexane and then with aqueous methanol, and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H-pyrazol-3-one was converted to 19 .05 g was obtained. This was analyzed by high performance liquid chromatography, the purity was calculated by an absolute calibration curve method, and the yield relative to the starting material 3-amino-4- (2-methylphenyl) -pyrazolin-5-one was determined. As a result, the purity was 97.6% and the yield was 83.0%. Moreover, when content of the urea compound as a by-product was calculated by an area percentage method, the content was 0.5%.
実施例２
実施例１と同様の反応器に、３−アミノ−４−（２−メチルフェニル）−ピラゾリン−５−オン１５．００ｇ（０．０７９モル）、メタノール３０．００ｇ、水５．３９ｇ、キシレン４５．００ｇ及び２５％水酸化ナトリウム水溶液１３．３２ｇを入れ攪拌した。この混合物に１５℃にてアリルクロロチオホルメート１０．６１ｇ（０．０７８モル）とキシレン９．１０ｇの混合物、及び１０％水酸化ナトリウム溶液３１．６４ｇをそれぞれ２時間かけて滴下し、滴下終了後、同温度でさらに２時間攪拌した。その後、反応混合物に２５℃にて１０％塩酸２７．９９ｇを３時間かけて滴下し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オンを析出させた。このときのｐＨは６．５であった。これにｎ−へキサン３０．００ｇを加え１時間攪拌後、ろ過した。ろ上物をｎ−へキサン、次いでメタノール水で洗浄し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オンを１９．１３ｇ得た。実施例１と同様に分析したところ、純度９７．３％、収率８３．４％であった。また、上記尿素化合物の含有量は０．９％であった。
Example 2
In the same reactor as in Example 1, 15.00 g (0.079 mol) of 3-amino-4- (2-methylphenyl) -pyrazolin-5-one, 30.00 g of methanol, 5.39 g of water, xylene 45 0.000 g and 25% aqueous sodium hydroxide solution 13.32 g were added and stirred. To this mixture, a mixture of 10.61 g (0.078 mol) of allyl chlorothioformate and 9.10 g of xylene and 31.64 g of 10% sodium hydroxide solution were added dropwise at 15 ° C. over 2 hours. Thereafter, the mixture was further stirred at the same temperature for 2 hours. Thereafter, 27.9 g of 10% hydrochloric acid was added dropwise to the reaction mixture at 25 ° C. over 3 hours, and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H— Pyrazol-3-one was precipitated. The pH at this time was 6.5. To this was added 30.00 g of n-hexane, and the mixture was stirred for 1 hour and filtered. The filtered product was washed with n-hexane and then with aqueous methanol, and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H-pyrazol-3-one was converted to 19 .13 g was obtained. When analyzed in the same manner as in Example 1, the purity was 97.3% and the yield was 83.4%. The urea compound content was 0.9%.
比較例１
実施例１と同様の反応器に、３−アミノ−４−（２−メチルフェニル）−ピラゾリン−５−オン１５．００ｇ（０．０７９モル）、メタノール３０．００ｇ、水５．３９ｇ、キシレン４５．００ｇ及び２５％水酸化ナトリウム水溶液１３．３２ｇを入れ攪拌した。この混合物に１５℃にてアリルクロロチオホルメート１０．６１ｇ（０．０７８モル）とキシレン９．１０ｇの混合物、及び１０％水酸化ナトリウム溶液３１．５９ｇをそれぞれ２時間かけて滴下し、滴下終了後、同温度でさらに２時間攪拌した。その後、反応混合物に２５℃にて１０％塩酸２８．８６ｇを1時間かけて滴下し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オンを析出させた。このときのｐＨは６．５であった。これにｎ−へキサン３０．００ｇを加え１時間攪拌後、ろ過した。ろ上物をｎ−へキサン、次いでメタノール水で洗浄し、１−〔（２−プロペニルチオ）カルボニル〕−４−（２−メチルフェニル）−５−アミノ−１Ｈ−ピラゾール−３−オンを１９．２８ｇ得た。実施例１と同様に分析したところ、純度９６．７％、収率８４．０％であった。上記尿素化合物の含有量は１．４％であった。
Comparative Example 1
In the same reactor as in Example 1, 15.00 g (0.079 mol) of 3-amino-4- (2-methylphenyl) -pyrazolin-5-one, 30.00 g of methanol, 5.39 g of water, xylene 45 0.000 g and 25% aqueous sodium hydroxide solution 13.32 g were added and stirred. To this mixture, a mixture of 10.61 g (0.078 mol) of allyl chlorothioformate and 9.10 g of xylene and 31.59 g of 10% sodium hydroxide solution were added dropwise at 15 ° C. over 2 hours. Thereafter, the mixture was further stirred at the same temperature for 2 hours. Thereafter, 28.86 g of 10% hydrochloric acid was added dropwise to the reaction mixture at 25 ° C. over 1 hour, and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H— Pyrazol-3-one was precipitated. The pH at this time was 6.5. To this was added 30.00 g of n-hexane, and the mixture was stirred for 1 hour and filtered. The filtered product was washed with n-hexane and then with aqueous methanol, and 1-[(2-propenylthio) carbonyl] -4- (2-methylphenyl) -5-amino-1H-pyrazol-3-one was converted to 19 .28 g was obtained. As a result of analysis in the same manner as in Example 1, the purity was 96.7% and the yield was 84.0%. The urea compound content was 1.4%.
Claims (2)
で示される化合物と一般式（２）
で示される化合物とを塩基存在下で反応させ、得られた反応混合物に酸を３時間以上かけて加えることにより、一般式（３）
で示される化合物を析出させることを特徴とする一般式（３）で示される化合物の製造方法。 General formula (1)
And a compound represented by the general formula (2)
Is reacted in the presence of a base, and an acid is added to the resulting reaction mixture over 3 hours to obtain a compound represented by the general formula (3).
A method for producing the compound represented by the general formula (3), wherein the compound represented by general formula (3) is precipitated.
The process according to claim 1, wherein the pH of the reaction mixture after addition of the acid is 5-9.
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| WO2009078475A1 (en) * | 2007-12-14 | 2009-06-25 | Sumitomo Chemical Company, Limited | Process for production of pyrazolinone derivative |
| JP2009298709A (en) * | 2008-06-11 | 2009-12-24 | Sumitomo Chemical Co Ltd | Method of preparing pyrazolinone derivative |
| WO2010143598A1 (en) * | 2009-06-08 | 2010-12-16 | 住友化学株式会社 | Method for purifying a pyrazolinone derivative |
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| WO2009078475A1 (en) * | 2007-12-14 | 2009-06-25 | Sumitomo Chemical Company, Limited | Process for production of pyrazolinone derivative |
| JP2009143850A (en) * | 2007-12-14 | 2009-07-02 | Sumitomo Chemical Co Ltd | Method of preparing pyrazolinone derivative |
| JP2009298709A (en) * | 2008-06-11 | 2009-12-24 | Sumitomo Chemical Co Ltd | Method of preparing pyrazolinone derivative |
| WO2010143598A1 (en) * | 2009-06-08 | 2010-12-16 | 住友化学株式会社 | Method for purifying a pyrazolinone derivative |
| US9296700B2 (en) | 2009-06-08 | 2016-03-29 | Sumitomo Chemical Company, Limited | Method for purifying a pyrazolinone derivative |
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