JPS63433B2

JPS63433B2 -

Info

Publication number: JPS63433B2
Application number: JP13791284A
Authority: JP
Inventors: Kenji Tsuzuki; Takeshi Uotani; Mitsuyuki Murakami
Original assignee: Tosoh Corp
Current assignee: Tosoh Corp
Priority date: 1984-07-05
Filing date: 1984-07-05
Publication date: 1988-01-07
Also published as: JPS6117563A

Description

[Detailed description of the invention]

〔産業上の利用分野〕本発明は、チオカーバメート誘導体の製造法に
関する。更に詳しくはアルキルフエニルクロロチ
オホルメイトとアミノピリジン誘導体を脱ハロゲ
ン化水素試剤の存在下に含水或いは無水のイソプ
ロパノール中で反応させることを特徴とするチオ
カーバメート誘導体の製造法に関する。チオカーバメート誘導体は、農薬、医薬として
有用な化合物である。〔従来の技術〕本発明のチオカーバメート誘導体の製造法に関
して、本発明者らは、アルキルフエニルクロロチ
オホルメイトとアミノピリジン誘導体を脱ハロゲ
ン化水素試剤存在下に反応させる方法を提案し
た。〔発明が解決しようとする問題点〕従来技術では高純度のチオカーバメート誘導体
を得るためにはカラムクロマトグラフイ或いは再
結晶等による精製を必要とし、工業操作上非常に
煩雑である。本発明の目的は、さらに工業的に有利に高純度
のチオカーバメート誘導体を製造することにあ
る。〔発明が解決するための手段〕本発明者らは、種々の試験をし、鋭意検討した
結果アルキルフエニルクロロチオホルメイトとア
ミノピリジン誘導体を脱ハロゲン化水素試剤存在
下に含水或いは、無水のイソプロパノール中で反
応させ次いで水を添加することによりカラムクロ
マトグラフイ或いは再結晶等の特別の精製を行う
ことなく、高純度のチオカーバメート誘導体を製
造できることを見い出した。すなわち、本発明は、一般式（）（式中R₁は、炭素数２〜５のアルキル基を示
す。）で表わされるアルキルフエニルクロロチオ
ホルメイトと一般式（）（式中R₂は水素原子、ハロゲン原子、低級アル
キル基、低級アルコキシ基を示す。）で表わされ
るアミノピリジン誘導体を脱ハロゲン化水素試剤
存在下に含水或いは無水のイソプロパノール中で
反応させ次いで水を添加することを特徴とする一般式（）（式中R₁、R₂は前に同じ、）で表わされるチオカ
ーバメート誘導体の製造法を提供するものであ
る。〔作用〕次に本発明の実施方法について詳しく述べる。
アミノピリジン誘導体と脱ハロゲン化水素試剤を
含水或いは無水のイソプロパノールに加える。次
いでアルキルフエニルクロロチオホルメイトを滴
下する。全量のアルキルフエニルクロロチオホル
メイトを滴下後に所定量の水を添加し反応生成物
であるチオカーバメート誘導体を析出させる。ま
た、その他にアルキルフエニルクロロチオホルメ
イトとアミノピリジン誘導体を反応させ生成させ
た塩化水素を脱ハロゲン化水素試剤と反応させ塩
（以下塩と呼ぶ）を析出せしめる。反応終了後、反応液を過しチオカーバメート
誘導体と塩を集める。次に集めたチオカーバメー
ト誘導体と塩を水で洗浄して塩を除去し高純度の
チオカーバメート誘導体を得る。アミノピリジン誘導体はアルキルフエニルクロ
ロチオホルメイトと等モル、また脱ハロゲン化水
素試剤は、それと当量以上用いる。脱ハロゲン化水素試剤としては、炭酸ナトリウ
ム、炭酸カリウム等の炭酸アルカリ塩、炭酸水素
ナトリウム、炭酸水素カリウム等の炭酸水素アル
カリ塩、そしてトリエチルアミン、ジメチルアニ
リン、ピリジン等の有機塩基を挙げることができ
る。そして、これらのアルコールは水を含んでいて
もよくアミノピリジン誘導体に対して約５〜約20
倍重量用いる。反応終了後に添加する水の量は、反応に用いる
アルコールと水の混合割合と関係あるが添加後の
アルコール−水溶液中の水の割合が30％未満では
高純度のチオカーバメート誘導体の回収率が低
く、70％を超えるとチオカーバメート誘導体の純
度が低下するためアルコール−水混合溶液中の水
の割合が30〜70％になる量が好ましい。反応温度は通常０℃から約50℃の間を選択す
る。反応時間は、通常10時間以内に完結させること
ができる。〔実施例〕次に実施例によつて本発明を詳細に説明する
が、本発明は、これら実施例のみに限定されるも
のではない。実施例１ 500mlの３つ口フラスコに２−メトキシ−６−
メチルアミノピリジン14.5gr.、炭酸ナトリウム
11.2gr.、10％含水イソプロパノール125mlを取り
室温にて撹拌しつつ４−tert−ブチルフエニルク
ロロチオホルメイト24.0gr.を20分間で滴下した。
滴下後さらに２時間撹拌し反応を完結させた。反応終了後、水245mlを添加しフラスコより内
容物を取り出し固体を過して集めた。次いで水
145mlにより固体を洗浄し、融点87〜88℃のＯ−
４−tert−ブチルフエニルＮ−メチル−Ｎ−
（６−メトキシ−２−ピリジル）チオカーバメー
ト33.8gr.を得た。（収率97.3％）高速液体クロマトグラフにより分析したところ
純度は99.7％であつた。比較例１ 500mlの３つ口フラスコに２−メトキシ−６−
メチルアミノピリジン14.5gr.、炭酸ナトリウム
11.2gr.、10％含水イソプロパノール125mlを取り
室温にて撹拌しつつ４−tert−ブチルフエニルク
ロロチオホルメイト24.0gr.を20分間で滴下した。
滴下後さらに２時間撹拌し反応を完結させた。反応終了後、水を添加することなくフラスコよ
り内容物を取り出し固体を過して集めた。次い
で水145mlにより固体を洗浄し融点87〜88℃のＯ
−４−tert−ブチルフエニルＮ−メチル−Ｎ−
（６−メトキシ−２−ピリジル）チオカーバメー
ト27.9gr.を得た。（収率79.7％）高速液体クロマトグラフにより分析したところ
純度は99.0％であつた。実施例２〜８および比較例２実施例１と同一の反応装置にアミノピリジン誘
導体、脱ハロゲン化水素試剤及び溶剤として含水
或いは無水のイソプロパノールを取りアルキルフ
エニルクロロチオホルメイトを滴下し第１表の条
件下で反応させた。反応終了後、実施例１と同一の反応操作により
チオカーバメート誘導体を得た。その結果を第１
表に示す。これらの場合の収率は94.7〜98.5％であつた。また、比較例２に溶媒としてアセトンを用いた
場合を示した。この場合の収率は80％であつた。さらに比較例３として反応後に添加した水の量
を400mlとした以外は実施例７と同様にして処理
したところ、Ｏ−４−エチルフエニルＮ−メチ
ル−Ｎ−（６−メトキシ−２−ピリジル）チオカ
ーバメイトの収量は32.7ｇおよび純度は97.5％で
あつた。 [Industrial Field of Application] The present invention relates to a method for producing thiocarbamate derivatives. More specifically, the present invention relates to a method for producing a thiocarbamate derivative, which is characterized by reacting an alkylphenyl chlorothioformate and an aminopyridine derivative in aqueous or anhydrous isopropanol in the presence of a dehydrohalogenating agent. Thiocarbamate derivatives are compounds useful as agricultural chemicals and medicines. [Prior Art] Regarding the method for producing the thiocarbamate derivative of the present invention, the present inventors proposed a method in which an alkylphenyl chlorothioformate and an aminopyridine derivative are reacted in the presence of a dehydrohalogenating agent. [Problems to be Solved by the Invention] In the prior art, in order to obtain highly pure thiocarbamate derivatives, purification by column chromatography or recrystallization is required, which is very complicated in terms of industrial operations. An object of the present invention is to further industrially advantageously produce highly pure thiocarbamate derivatives. [Means for Solving the Invention] As a result of various tests and intensive studies, the present inventors have determined that an alkyl phenyl chlorothioformate and an aminopyridine derivative can be prepared in the presence of a dehydrohalogenating agent in a hydrous or anhydrous form. It has been found that a highly pure thiocarbamate derivative can be produced without special purification such as column chromatography or recrystallization by reacting in isopropanol and then adding water. That is, the present invention is based on the general formula () (In the formula, R ₁ represents an alkyl group having 2 to 5 carbon atoms.) and an alkyl phenyl chlorothioformate represented by the general formula () (In the formula, R ₂ represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group.) An aminopyridine derivative represented by the formula (R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group) is reacted in aqueous or anhydrous isopropanol in the presence of a dehydrohalogenation reagent, and then water is added. General formula () characterized by the addition of The present invention provides a method for producing a thiocarbamate derivative represented by the formula (wherein R ₁ and R ₂ are the same as above). [Function] Next, the method of implementing the present invention will be described in detail.
An aminopyridine derivative and a dehydrohalogenating agent are added to aqueous or anhydrous isopropanol. Then the alkyl phenyl chlorothioformate is added dropwise. After dropping the entire amount of alkylphenyl chlorothioformate, a predetermined amount of water is added to precipitate a thiocarbamate derivative, which is a reaction product. In addition, hydrogen chloride produced by reacting an alkylphenyl chlorothioformate with an aminopyridine derivative is reacted with a dehydrohalogenation reagent to precipitate a salt (hereinafter referred to as salt). After the reaction is completed, the reaction solution is filtered to collect the thiocarbamate derivative and salt. Next, the collected thiocarbamate derivative and salt are washed with water to remove the salt and obtain a highly pure thiocarbamate derivative. The aminopyridine derivative is used in an equimolar amount to the alkyl phenyl chlorothioformate, and the dehydrohalogenation reagent is used in an equivalent or more amount. Examples of dehydrohalogenation reagents include alkali carbonates such as sodium carbonate and potassium carbonate, alkali hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, and organic bases such as triethylamine, dimethylaniline, and pyridine. These alcohols may contain water and have a concentration of about 5 to about 20% relative to the aminopyridine derivative.
Use double weight. The amount of water added after the reaction is related to the mixing ratio of alcohol and water used in the reaction, but if the ratio of water in the alcohol-aqueous solution after addition is less than 30%, the recovery rate of high-purity thiocarbamate derivatives will be low. If it exceeds 70%, the purity of the thiocarbamate derivative decreases, so the amount is preferably such that the proportion of water in the alcohol-water mixed solution is 30 to 70%. The reaction temperature is usually selected between 0°C and about 50°C. The reaction time can usually be completed within 10 hours. [Examples] Next, the present invention will be explained in detail with reference to Examples, but the present invention is not limited to these Examples. Example 1 2-methoxy-6- in a 500 ml three-necked flask
Methylaminopyridine 14.5gr., Sodium Carbonate
125 ml of 11.2 gr., 10% water-containing isopropanol was taken, and while stirring at room temperature, 24.0 gr. of 4-tert-butylphenylchlorothioformate was added dropwise over 20 minutes.
After the dropwise addition, the mixture was further stirred for 2 hours to complete the reaction. After the reaction was completed, 245 ml of water was added, the contents were taken out from the flask, and the solid was collected by filtration. Then water
Wash the solid with 145 ml of O-
4-tert-butylphenyl N-methyl-N-
33.8 gr. of (6-methoxy-2-pyridyl)thiocarbamate was obtained. (Yield 97.3%) Analysis by high performance liquid chromatography showed that the purity was 99.7%. Comparative example 1 2-methoxy-6- in a 500ml three-necked flask
Methylaminopyridine 14.5gr., Sodium Carbonate
125 ml of 11.2 gr., 10% water-containing isopropanol was taken, and while stirring at room temperature, 24.0 gr. of 4-tert-butylphenylchlorothioformate was added dropwise over 20 minutes.
After the dropwise addition, the mixture was further stirred for 2 hours to complete the reaction. After the reaction was completed, the contents were taken out from the flask without adding water, and the solids were collected by filtration. The solid was then washed with 145 ml of water and dissolved in O with a melting point of 87-88°C.
-4-tert-butylphenyl N-methyl-N-
27.9 gr. of (6-methoxy-2-pyridyl)thiocarbamate was obtained. (Yield 79.7%) Analysis by high performance liquid chromatography showed that the purity was 99.0%. Examples 2 to 8 and Comparative Example 2 Into the same reaction apparatus as in Example 1, an aminopyridine derivative, a dehydrohalogenation reagent, and aqueous or anhydrous isopropanol were taken as a solvent, and alkyl phenyl chlorothioformate was added dropwise to the reactor shown in Table 1. The reaction was carried out under the following conditions. After the reaction was completed, a thiocarbamate derivative was obtained by the same reaction procedure as in Example 1. The result is the first
Shown in the table. The yield in these cases was 94.7-98.5%. Further, Comparative Example 2 shows a case where acetone was used as a solvent. The yield in this case was 80%. Further, as Comparative Example 3, treatment was carried out in the same manner as in Example 7 except that the amount of water added after the reaction was changed to 400 ml. The yield of carbamate was 32.7 g and the purity was 97.5%.

【表】【table】

〔Effect of the invention〕

この様にして本製造法の目的物のチオカーバメ
ート誘導体を再結晶等の特別の精製をすることな
く高純度、高収率で得ることができる。又副反応による溶媒損失などの防止と、副生成
物によるチオカーバメート誘導体の汚染防止に極
めて有効である。 In this way, the target thiocarbamate derivative of the present production method can be obtained with high purity and high yield without special purification such as recrystallization. It is also extremely effective in preventing solvent loss due to side reactions and in preventing contamination of thiocarbamate derivatives by by-products.

Claims

[Claims] 1 General formula () (In the formula, R ₁ represents an alkyl group having 2 to 5 carbon atoms.)
Alkylphenyl chlorothioformate represented by general formula () (In the formula, R ₂ represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group.) An aminopyridine derivative represented by the formula (R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group) is reacted in water-containing or anhydrous isopropanol in the presence of a dehydrohalogenation reagent, and then water General formula () characterized by the addition of (In the formula, R ₁ and R ₂ are the same as before.) A method for producing a thiocarbamate derivative.