JP3569877B2 - Method for producing m-substituted-α-hydroxymethylstyrene derivative and 3-chloro-α-bromostyrene - Google Patents

Description

【０００５】
および下記一般式（２）
【０００６】
【化２０】

（上記式中、Ｒ¹ は塩素原子、フッ素原子、トリフルオロメチル基、炭素数１〜１０のアルキル基、炭素数１〜１０のアルコキシル基を示す）で表されるｍ−置換−α−ブロモスチレン誘導体に金属マグネシウムを反応させて、下記一般式（３）
【０００７】
【化２１】

【０００８】
（上記＼式中、Ｒ¹ は式（２）の定義と同一の意義を有す）で表されるグリニャール試薬を得、次いで当該グリニャール試薬をホルムアルデヒドあるいはパラホルムアルデヒドと反応させることを特徴とする下記一般式（４）
【０００９】
【化２２】

【００１０】
（上記式中、Ｒ¹ は式（２）の定義と同一の意義を有す）で表されるｍ−置換−α−ヒドロキシメチルスチレン誘導体の製造法、および上記反応で出発原料として用いられる下記式（２）で表されるｍ−置換−α−ブロモスチレン誘導体の製造法に存する。
【００１１】
以下、本発明を詳細に説明する。
上記一般式（２）、（３）および（４）において、Ｒ¹ は塩素原子；フッ素原子；トリフロオロメチル基；メチル基、エチル基、プロピル基、ブチル基、ペンチル基、iso-プロピル基、tert- ブチル基等の直鎖状またはこれらの基を側鎖に有する分岐状の炭素数１〜１０のアルキル基；メトキシ基、エトキシ基、プロポキシ基、iso-プロポキシ基、tert- ブトキシ基等の炭素数１〜１０のアルコキシ基を示す。これらの中でＲ¹ としては塩素原子が最も好ましい。
本発明では、下記一般式（２）
【００１２】
【化２３】

【００１３】
（上記式中、Ｒ¹ は前記の定義と同一の意義を有す）で表されるｍ−置換−α−ブロモスチレン誘導体に対し、常法に従って金属マグネシウムを反応させて、下記一般式（３）
【００１４】
【化２４】

【００１５】
（上記式中、Ｒ¹ は前記の定義と同一の意義を有す）で表されるグリニャール試薬を得、次いで当該グリニャール試薬をホルムアルデヒドあるいはパラホルムアルデヒドと反応させることにより、下記一般式（４）
【００１６】
【化２５】

【００１７】
（上記式中、Ｒ¹ は前記の定義と同一の意義を有す）で表されるｍ−置換−α−ヒドロキシメチルスチレン誘導体を製造する。
【００１８】
本発明のｍ−置換−α−ヒドロキシメチルスチレン誘導体の製造法において、金属マグネシウムはｍ−置換−α−ブロモスチレンに対し、通常５０〜１５０モル％、好ましくは８０〜１２０モル％用いる。
反応は、通常溶媒を用いて行われ、用いる溶媒としては、ジエチルエーテル、テトラヒドロフラン、ジブチルエーテル等のエーテル系溶媒が好適である。溶媒の使用量は、上記一般式（２）のｍ−置換−α−ブロモスチレンに対して、通常１〜１００倍量（重量）、好ましくは１〜１５倍量である。
【００１９】
本反応では、前記一般式（２）のｍ−置換−α−ブロモスチレンをエーテル系溶媒とマグネシウムの混合物中に徐々に滴下し、通常０〜１００℃、好ましくは２０〜７０℃で、滴下終了後５分〜２時間、マグネシウムと反応させる。反応の際、少量のヨウ素、ジブロムエタン等を共存させてもよい。
反応終了後、室温で放置して反応を完結させた後、次いで得られたグリニャール試薬に
ホルムアルデヒドあるいはパラホルムアルデヒドを加え反応させる。ホルムアルデヒドあるいはパラホルムアルデヒドの使用量は特に制限されるものではないが、前記一般式（２）のｍ−置換−α−ブロモスチレンに対して、５０〜２００モル％用いるのが良い。グリニャール試薬とホルムアルデヒドあるいはパラホルムアルデヒドとの反応における反応温度は、通常−１０〜１５０℃、好ましくは０〜８０℃の範囲で実施される。
反応終了後、反応液を酸性とし、有機溶媒と接触させ抽出を行い、蒸留、カラムクロマトグラフィー等を行うことにより、ｍ−置換−α−ヒドロキシメチルスチレンを容易に単離精製することができる。使用できる有機溶媒としては、例えば、ジエチルエーテル等のエーテル系溶媒、酢酸エチル等のエステル系溶媒、ヘキサン等の脂肪族炭化水素系溶媒、トルエン等の芳香族炭化水素系溶媒が挙げられる。
【００２０】
本発明のｍ−置換−α−ヒドロキシメチルスチレンの製造法において、原料として使用される、前記一般式（２）のｍ−置換−α−ブロモスチレン誘導体は、例えば、以下の３種の工業的に有利な方法によって容易に製造することができる。
すなわち、下記一般式（７）
【００２１】
【化２６】

【００２２】
（Ｒ¹ は前記の定義と同一の意義を有す）で表されるｍ−置換−α，β−ジブロモエチルベンゼン誘導体に塩基を作用させることにより、前記一般式（２）のｍ−置換−α−ブロモスチレン誘導体を製造することができる。この脱臭化水素反応に用いられる塩基としては、水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸カルシウム等の無機塩基および、トリエチルアミン、１，８−ジアザビシクロ［５・４・０］−７−ウンデセン（ＤＢＵ）、ピリジン等の有機塩基等が挙げられる。反応に用いられる溶媒には特に制限は無く、無溶媒あるいはヘキサン、ベンゼン等の炭化水素系溶媒、メタノール、エタノール等のアルコール系溶媒、ジエチルエーテル、テトラヒドロフラン等のエーテル系溶媒等が用いられる。脱臭化水素反応は通常０〜１２０℃で、５〜２時間行われる。
【００２３】
なお、上記一般式（７）のｍ−置換−α，β−ジブロモエチルベンゼン誘導体は、ｍ−置換−スチレン誘導体に臭素を反応させることにより、容易に製造することができる。
また、下記一般式（８）
【００２４】
【化２７】

【００２５】
（Ｒ¹ は前記の定義と同一の意義を有す）で表されるｍ−置換−α，α−ジブロモエチル
ベンゼン誘導体に塩基を作用させることにより式（２）のｍ−置換−α−ブロモスチレン誘導体を製造することができる。この脱臭化水素反応に用いられる塩基としては、水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸カルシウム等の無機塩基および、トリエチルアミン、ＤＢＵ、ピリジン等の有機塩基等が挙げられる。反応に用いられる溶媒に特に制限はなく、無溶媒あるいはヘキサン、ベンゼン等の炭化水素系溶媒、メタノール、エタノール等のアルコール系溶媒、ジエチルエーテル、テトラヒドロフラン等のエーテル系溶媒等が用いられる。本反応は、通常０〜１２０℃で、５分〜２時間行われる。
【００２６】
なお、上記一般式（８）のｍ−置換−α，α−ジブロモエチルベンゼン誘導体は、ｍ−置換−エチルベンゼン誘導体に適当なラジカル開始剤の存在下（例えば、光照射あるいは触媒量の過酸化物存在下）で臭素を反応させることにより、容易に製造することができる。
さらに、下記式（９）
【００２７】
【化２８】

【００２８】
（Ｒ¹ は前記の定義と同一の意義を有す）で表されるｍ−置換−アセトフェノン誘導体に三臭化リンを作用させることにより式（２）のｍ−置換−α−ブロモスチレン誘導体を製造することができる。この反応は、無溶媒あるいは有機酸溶媒下で行われ、使用される有機酸としては、例えば、酢酸、メタンスルホン酸、トリクロロ酢酸等が用いられる。溶媒の使用量は、特に制限されるものではないが、通常０〜１００倍量（重量）、好ましくは０〜１０倍量がとする。本反応に用いられる三臭化リンの使用量は、式（９）のｍ−置換−アセトフェノン誘導体に対し、通常５０〜２０００モル％、好ましくは８０〜１０００モル％が適当である。反応は、通常０〜２００℃、好ましくは２０〜１５０℃の範囲で、３０分〜５時間程度行う。
【００２９】
ここで、前記一般式（２）のｍ−置換−α−ブロモスチレン誘導体においてＲ¹ が塩素原子である化合物，ずなわち３−クロロ−α−ブロモスチレンは新規化合物であり、上記と同様の方法により製造することができる。
以上の３つの方法によって製造された式（２）のｍ−置換−α−ブロモスチレン誘導体は、いずれも常法にて後処理を行い、蒸留あるいはカラムクロマトグラフィー等を行うことにより、容易に単離、精製することができる。
【００３０】
【実施例】
以下、本発明を実施例を挙げてさらに詳細に説明するが、本発明はその要旨を越えない限り、以下の実施例に限定されるものではない。
実施例１ ３−クロロ−α−ヒドロキシメチルスチレンの合成
マグネシウム０．４４ｇ、テトラヒドロフラン１０ｍｌの混合物に少量のヨウ素を加え、次いで３−クロロ−α−ブロモスチレン４．０ｇをテトラヒドロフラン１０ｍｌに溶解した溶液を、２０℃で５分間かけて滴下した。滴下終了後、２０℃で１時間撹拌した後、氷浴で冷却した反応混合物中にホルムアルデヒド約０．８ｇを吹き込み、そのまま１時間さらに撹拌した。反応混合物を氷冷下、１０％塩酸水５０ｍｌを加えて酸性とし、氷冷下さらに３０分間撹拌した後、ジエチルエーテル５０ｍｌで２回抽出した。抽出液を無水硫
酸ナトリウムで乾燥し濃縮し、シリカゲルカラムクロマトグラフィーにて単離精製したところ、３−クロロ−（α−ヒドロキシメチル）スチレン３．５ｇを得た。その収率は３−クロロ−α−ブロモスチレンに対し８０．０％であった。
【００３１】
比較例１ ３−クロロ−α−ヒドロキシメチルスチレンの合成
テトラヒドロフラン８５ｍｌ、マグネシウム８．２ｇの混合物中に１，３−ジクロロベンゼン５ｇと、少量のヨウ素を加えた。反応が始まり次第、１，３−ジクロロベンゼン４５ｇを内温を６０〜６５℃に保ちながらプロパルギルアルコール９．５ｇを滴下した。６０℃にて３０分間反応した後、氷冷下、塩酸水を加えて反応系を酸性にし、室温にて３０分間撹拌した。不溶物を濾別した後、濾液に酢酸エチル、飽和食塩水を加えて分液し、有機層を無水硫酸ナトリウムにて乾燥し濃縮した。得られた残渣を蒸留にて生成したところ、３−クロロ−（α−ヒドロキシメチル）スチレン１７．１ｇを得た。その収率はプロパルギルアルコールに対し５９．７％であった。
【００３２】
実施例２ ３−クロロ−α−ブロモスチレンの合成
３−クロロ−α，β−ジブロモエチルベンゼン２０ｇに水酸化カリウム２０ｇのエタノール溶液２００ｍｌを室温で滴下し、滴下終了後、さらに室温で１時間撹拌した。反応終了後、反応液を氷冷水３００ｍｌに注ぎ、エーテル２００ｍｌで抽出を行い、抽出液を無水硫酸ナトリウムで乾燥し濃縮したところ、３−クロロ−α−ブロモスチレン３．５ｇを得た。
【００３３】
実施例３ ３−クロロ−α−ブロモスチレンの合成
３−クロロ−α，α−ジブロモエチルベンゼン２０ｇに水酸化カリウム２０ｇのエタノール溶液２００ｍｌを室温で滴下し、滴下終了後、６０℃で１時間撹拌した。反応終了後、反応液を氷冷水３００ｍｌに注ぎ、エーテル２００ｍｌで抽出を行い、抽出液を無水硫酸ナトリウムで乾燥し濃縮したところ、３−クロロ−α−ブロモスチレン３．５ｇを得た。
【００３４】
実施例４ ３−クロロ−α−ブロモスチレンの合成
３−クロロアセトフェノン２０ｇと酢酸１００ｍｌの溶液に三臭化リン１００ｇを室温で加え、次いで７０℃に昇温し、３時間反応させた。反応液をガスクロマトグラフィーにより分析、定量したところ、３−クロロ−α−ブロモスチレンが３５％（３−クロロアセトフェノンに対する収率として）生成していた。
【００３５】
実施例５ ３−クロロ−α−ブロモスチレンの合成
３−クロロアセトフェノン２０ｇと酢酸１００ｍｌの溶液に三臭化リン１００ｇを室温で加え、次いで１５０℃に昇温し、６時間反応させた。反応液をガスクロマトグラフィーにより分析、定量したところ、３−クロロ−α−ブロモスチレンが３５％（３−クロロアセトフェノンに対する収率として）生成していた。
【００３６】
【発明の効果】
本発明の３−クロロ−α−ブロモスチレンは除草剤等の中間体として有用であり、また本発明の製造法によれば、ｍ−置換−α−ヒドロキシメチルスチレンを高収率で容易に得ることができ、本発明の工業的価値は高い。[0001]
[Industrial applications]
The present invention relates to a method for producing an m-substituted-α-hydroxymethylstyrene derivative useful as an intermediate for medicines and agricultural chemicals, particularly as an intermediate for herbicides.
[0002]
2. Description of the Related Art
m-Substituted α-hydroxymethylstyrene derivatives, among which 3-chloro-α-hydroxymethylstyrene are particularly useful compounds as intermediates for herbicides described in JP-A-2-304443. .
Conventionally, as a method for producing 3-chloro- (α-hydroxymethyl) styrene, a Grignard reagent is obtained from 1,3-dichlorobenzene and magnesium in tetrahydrofuran, and the Grignard reagent is further added to propargyl alcohol and a catalytic amount of iodide. A production method of reacting in the presence of copper is known.
However, the above-mentioned production method has a problem that the yield is as low as about 60%, and a Grignard reagent of 2 equivalents or more with respect to propargyl alcohol is required.
[0003]
[Means for Solving the Problems]
The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, by reacting m-substituted-α-bromostyrene derivative with metallic magnesium to obtain a Grignard reagent and then reacting with formaldehyde, a high yield is obtained. The inventors have found that an m-substituted-α-hydroxymethylstyrene derivative can be obtained, and have completed the present invention.
That is, the gist of the present invention is to provide 3-chloro-α-bromostyrene represented by the following formula (1):
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[0005]
And the following general formula (2)
[0006]
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(In the above formula, R ¹ represents a chlorine atom, a fluorine atom, a trifluoromethyl group, an alkyl group having 1 to 10 carbon atoms, or an alkoxyl group having 1 to 10 carbon atoms.) By reacting styrene derivative with metallic magnesium, the following general formula (3)
[0007]
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[0008]
(Wherein R ¹ has the same meaning as defined in formula (2)), and then reacting the Grignard reagent with formaldehyde or paraformaldehyde. General formula (4)
[0009]
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[0010]
(Wherein R ¹ has the same meaning as defined in formula (2)), a method for producing an m-substituted-α-hydroxymethylstyrene derivative represented by the following formula: The present invention relates to a method for producing an m-substituted-α-bromostyrene derivative represented by the formula (2).
[0011]
Hereinafter, the present invention will be described in detail.
In the general formulas (2), (3) and (4), R ¹ is a chlorine atom; a fluorine atom; a trifluoromethyl group; a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, an iso-propyl group. Linear or branched alkyl groups having 1 to 10 carbon atoms, such as tert-butyl and the like, in the side chain; methoxy, ethoxy, propoxy, iso-propoxy, tert-butoxy, etc. Represents an alkoxy group having 1 to 10 carbon atoms. Among them, a chlorine atom is most preferred as R ¹ .
In the present invention, the following general formula (2)
[0012]
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[0013]
(In the above formula, R ¹ has the same meaning as defined above), and reacted with metallic magnesium in accordance with a conventional method with an m-substituted-α-bromostyrene derivative to obtain a compound represented by the following general formula (3) )
[0014]
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[0015]
(Wherein R ¹ has the same meaning as defined above), and then reacting the Grignard reagent with formaldehyde or paraformaldehyde to obtain the following general formula (4)
[0016]
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[0017]
(Wherein R ¹ has the same meaning as defined above) to produce an m-substituted-α-hydroxymethylstyrene derivative.
[0018]
In the method for producing an m-substituted-α-hydroxymethylstyrene derivative of the present invention, metallic magnesium is used in an amount of usually 50 to 150 mol%, preferably 80 to 120 mol%, based on m-substituted α-bromostyrene.
The reaction is usually performed using a solvent, and as the solvent to be used, ether solvents such as diethyl ether, tetrahydrofuran, dibutyl ether and the like are preferable. The amount of the solvent to be used is generally 1- to 100-fold (weight), preferably 1- to 15-fold, the amount of the m-substituted-α-bromostyrene of the general formula (2).
[0019]
In this reaction, the m-substituted-α-bromostyrene of the general formula (2) is gradually dropped into a mixture of an ether solvent and magnesium, and the dropping is usually completed at 0 to 100 ° C, preferably 20 to 70 ° C. React with magnesium for another 5 minutes to 2 hours. At the time of the reaction, a small amount of iodine, dibromoethane or the like may be allowed to coexist.
After completion of the reaction, the reaction is left at room temperature to complete the reaction, and then the obtained Grignard reagent is reacted by adding formaldehyde or paraformaldehyde. The amount of formaldehyde or paraformaldehyde to be used is not particularly limited, but is preferably 50 to 200 mol% based on the m-substituted-α-bromostyrene of the general formula (2). The reaction temperature of the reaction between the Grignard reagent and formaldehyde or paraformaldehyde is usually in the range of -10 to 150C, preferably 0 to 80C.
After completion of the reaction, the reaction solution is acidified, extracted by bringing it into contact with an organic solvent, and subjected to distillation, column chromatography and the like, whereby the m-substituted-α-hydroxymethylstyrene can be easily isolated and purified. Examples of usable organic solvents include ether solvents such as diethyl ether, ester solvents such as ethyl acetate, aliphatic hydrocarbon solvents such as hexane, and aromatic hydrocarbon solvents such as toluene.
[0020]
In the method for producing m-substituted-α-hydroxymethylstyrene of the present invention, the m-substituted-α-bromostyrene derivative of the general formula (2) used as a raw material may be, for example, the following three types of industrial materials: Can be easily manufactured by a method advantageous to
That is, the following general formula (7)
[0021]
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[0022]
(R ¹ has the same meaning as defined above) by reacting a base on the m-substituted-α, β-dibromoethylbenzene derivative to obtain the m-substituted-α of the general formula (2). -Bromostyrene derivatives can be produced. Examples of the base used in the dehydrobromination reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, and calcium carbonate, and triethylamine, 1,8-diazabicyclo [5.4.0] -7-undecene ( Organic bases such as DBU) and pyridine. The solvent used in the reaction is not particularly limited, and no solvent or a hydrocarbon solvent such as hexane and benzene, an alcohol solvent such as methanol and ethanol, and an ether solvent such as diethyl ether and tetrahydrofuran are used. The dehydrobromination reaction is usually performed at 0 to 120 ° C. for 5 to 2 hours.
[0023]
In addition, the m-substituted-α, β-dibromoethylbenzene derivative of the general formula (7) can be easily produced by reacting bromine with the m-substituted-styrene derivative.
The following general formula (8)
[0024]
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[0025]
(R ¹ has the same meaning as defined above) by reacting a base on the m-substituted- α, α -dibromoethylbenzene derivative represented by the formula (2) to obtain an m-substituted-α-bromostyrene of the formula (2) Derivatives can be produced. Examples of the base used in the dehydrobromination reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, and calcium carbonate, and organic bases such as triethylamine, DBU, and pyridine. There is no particular limitation on the solvent used in the reaction, and no solvent or a hydrocarbon solvent such as hexane or benzene, an alcohol solvent such as methanol or ethanol, or an ether solvent such as diethyl ether or tetrahydrofuran is used. This reaction is usually performed at 0 to 120 ° C. for 5 minutes to 2 hours.
[0026]
The m-substituted- α, α -dibromoethylbenzene derivative of the general formula (8) can be prepared by adding an appropriate radical initiator to the m-substituted-ethylbenzene derivative (for example, by irradiation with light or the presence of a catalytic amount of peroxide). The reaction can be easily carried out by reacting bromine in (b).
Further, the following equation (9)
[0027]
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[0028]
(R ¹ has the same meaning as defined above) by reacting phosphorus-tribromide with the m-substituted-acetophenone derivative represented by the formula (2) to form the m-substituted-α-bromostyrene derivative of the formula (2). Can be manufactured. This reaction is carried out without a solvent or under an organic acid solvent, and examples of the organic acid used include acetic acid, methanesulfonic acid, and trichloroacetic acid. The amount of the solvent used is not particularly limited, but is usually 0 to 100 times (weight), preferably 0 to 10 times. The amount of phosphorus tribromide used in this reaction is usually 50 to 2000 mol%, preferably 80 to 1000 mol%, based on the m-substituted-acetophenone derivative of the formula (9). The reaction is carried out usually at 0 to 200 ° C, preferably 20 to 150 ° C, for about 30 minutes to 5 hours.
[0029]
Here, in the m-substituted-α-bromostyrene derivative of the general formula (2), a compound in which R ¹ is a chlorine atom, that is, 3-chloro-α-bromostyrene is a novel compound. It can be manufactured by a method.
All of the m-substituted-α-bromostyrene derivatives of the formula (2) produced by the above three methods can be easily treated simply by post-treatment and distillation or column chromatography. Can be separated and purified.
[0030]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist.
Example 1 Synthesis of 3-chloro-α-hydroxymethylstyrene A small amount of iodine was added to a mixture of 0.44 g of magnesium and 10 ml of tetrahydrofuran, and then a solution obtained by dissolving 4.0 g of 3-chloro-α-bromostyrene in 10 ml of tetrahydrofuran was added. At 20 ° C. over 5 minutes. After completion of the dropwise addition, the mixture was stirred at 20 ° C. for 1 hour, and then about 0.8 g of formaldehyde was blown into the reaction mixture cooled in an ice bath, and the mixture was further stirred for 1 hour. The reaction mixture was acidified by adding 50 ml of 10% hydrochloric acid under ice-cooling, stirred for another 30 minutes under ice-cooling, and extracted twice with 50 ml of diethyl ether. The extract was dried over anhydrous sodium sulfate, concentrated, and isolated and purified by silica gel column chromatography to obtain 3.5 g of 3-chloro- (α-hydroxymethyl) styrene. The yield was 80.0% based on 3-chloro-α-bromostyrene.
[0031]
Comparative Example 1 Synthesis of 3-chloro-α-hydroxymethylstyrene In a mixture of 85 ml of tetrahydrofuran and 8.2 g of magnesium, 5 g of 1,3-dichlorobenzene and a small amount of iodine were added. Immediately after the start of the reaction, 9.5 g of propargyl alcohol was added dropwise while maintaining the internal temperature of 60 g to 65 ° C. of 45 g of 1,3-dichlorobenzene. After reacting at 60 ° C. for 30 minutes, the reaction system was made acidic by adding hydrochloric acid under ice-cooling, followed by stirring at room temperature for 30 minutes. After filtering off the insoluble matter, ethyl acetate and saturated saline were added to the filtrate, and the mixture was separated. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was distilled to yield 17.1 g of 3-chloro- (α-hydroxymethyl) styrene. The yield was 59.7% based on propargyl alcohol.
[0032]
Example 2 Synthesis of 3-chloro-α-bromostyrene To 200 g of 3-chloro-α, β-dibromoethylbenzene, 200 ml of an ethanol solution of 20 g of potassium hydroxide was added dropwise at room temperature. After completion of the addition, the mixture was further stirred at room temperature for 1 hour. . After the completion of the reaction, the reaction solution was poured into 300 ml of ice-cold water, extracted with 200 ml of ether, and the extract was dried over anhydrous sodium sulfate and concentrated to obtain 3.5 g of 3-chloro-α-bromostyrene.
[0033]
Example 3 Synthesis of 3-chloro-α-bromostyrene To 200 g of 3-chloro- α, α -dibromoethylbenzene, 200 ml of an ethanol solution of 20 g of potassium hydroxide was added dropwise at room temperature. After completion of the addition, the mixture was stirred at 60 ° C. for 1 hour. . After the completion of the reaction, the reaction solution was poured into 300 ml of ice-cold water, extracted with 200 ml of ether, and the extract was dried over anhydrous sodium sulfate and concentrated to obtain 3.5 g of 3-chloro-α-bromostyrene.
[0034]
Example 4 Synthesis of 3-chloro-α-bromostyrene To a solution of 20 g of 3-chloroacetophenone and 100 ml of acetic acid was added 100 g of phosphorus tribromide at room temperature, and then the temperature was raised to 70 ° C. and reacted for 3 hours. The reaction solution was analyzed and quantified by gas chromatography, and as a result, 35% of 3-chloro-α-bromostyrene was produced (as a yield based on 3-chloroacetophenone).
[0035]
Example 5 Synthesis of 3-chloro-α-bromostyrene To a solution of 20 g of 3-chloroacetophenone and 100 ml of acetic acid was added 100 g of phosphorus tribromide at room temperature, and then the temperature was raised to 150 ° C. and reacted for 6 hours. The reaction solution was analyzed and quantified by gas chromatography, and as a result, 35% of 3-chloro-α-bromostyrene was produced (as a yield based on 3-chloroacetophenone).
[0036]
【The invention's effect】
The 3-chloro-α-bromostyrene of the present invention is useful as an intermediate such as a herbicide, and according to the production method of the present invention, m-substituted α-hydroxymethylstyrene can be easily obtained in high yield. Therefore, the industrial value of the present invention is high.

Claims (8)

3-chloro-α-bromostyrene of the following formula (1).

The following general formula (2)

(In the above formula, R ¹ represents a chlorine atom, a fluorine atom, a trifluoromethyl group, an alkyl group having 1 to 10 carbon atoms or an alkoxyl group having 1 to 10 carbon atoms). By reacting styrene derivative with metallic magnesium, the following general formula (3)

(Wherein R ¹ has the same meaning as defined in formula (2)), and then reacting the Grignard reagent with formaldehyde or paraformaldehyde. Equation (4)

(Wherein R ¹ has the same meaning as the definition of formula (2)). A method for producing an m-substituted α-hydroxymethylstyrene derivative represented by the following formula: The following formula (5) is obtained by reacting 3-chloro-α-bromostyrene according to claim 1 with metallic magnesium.

Wherein the Grignard reagent is reacted with formaldehyde or paraformaldehyde.

For producing 3-chloro-α-hydroxymethylstyrene. The following general formula (7)

(Wherein R ¹ has the same meaning as defined in formula (2)), wherein a base is allowed to act on the m-substituted-α, β-dibromoethylbenzene derivative represented by the following general formula: (2)

(In the formula, R ¹ is the formula (having a definition identical to the meaning of the 2)) the preparation of m- substituted -α- bromostyrene derivative represented by the. The following general formula (8)

(Wherein R ¹ has the same meaning as defined in formula (2)), wherein a base is allowed to act on the m-substituted- α, α -dibromoethylbenzene derivative represented by the following general formula: (2)

(In the formula, R ¹ is the formula (having a definition identical to the meaning of the 2)) the preparation of m- substituted -α- bromostyrene derivative represented by the. The following equation (10)

Wherein a base is allowed to act on 3-chloro-α, β-dibromoethylbenzene of the following formula (1):

For producing 3-chloro-α-bromostyrene. The following equation (11)

Wherein a base is allowed to act on 3-chloro- α, α -dibromoethylbenzene of the following formula (1):

Production method of 3-chloro-α-bromostyrene. The following equation (12)

Wherein phosphorus tribromide is allowed to act on 3-chloro-acetophenone of the following formula (1):

For producing 3-chloro-α-bromostyrene.