JPH045255A - Method for producing phenoxyalkane carboxylic acid derivatives - Google Patents
Method for producing phenoxyalkane carboxylic acid derivativesInfo
- Publication number
- JPH045255A JPH045255A JP2106388A JP10638890A JPH045255A JP H045255 A JPH045255 A JP H045255A JP 2106388 A JP2106388 A JP 2106388A JP 10638890 A JP10638890 A JP 10638890A JP H045255 A JPH045255 A JP H045255A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- mol
- carboxylic acid
- producing
- general formula
- 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
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明はフェノキシアルカンカルボン酸誘導体の製造方
法に関し、更に詳しくは、医薬品として有用なカルコン
誘導体の製造に極めて有用なフェノキシアルカンカルボ
ン酸誘導体を簡便にしかも高収率で得る新規な製造方法
を提供するものである。Detailed Description of the Invention (Industrial Application Field) The present invention relates to a method for producing phenoxyalkane carboxylic acid derivatives, and more specifically, a method for easily producing phenoxy alkane carboxylic acid derivatives, which are extremely useful for producing chalcone derivatives useful as pharmaceuticals. Moreover, it provides a novel manufacturing method that can obtain high yields.
（従来の技術）
従来、かかる化合物は前記一般式（１）で示されるフェ
ノ−１６体をモノハロゲノアルカンカルボン酸と反応さ
せることにより、あるいはモノハロゲノアルカンカルボ
ン酸エステルと反応させることにより合成できることが
知られている。(Prior Art) Conventionally, it has been known that such a compound can be synthesized by reacting the pheno-16 compound represented by the general formula (1) with a monohalogenoalkanecarboxylic acid or a monohalogenoalkanecarboxylic acid ester. Are known.
これらの従来法は工業的製造法として満足しうるちので
はなく、いくつかの欠点を有している。These conventional methods are not satisfactory as industrial production methods and have several drawbacks.
例えば、モノハロゲのアルカンカルボン酸をアルキル化
剤として用いた場合、反応系内で一旦アルカリ塩にして
から反応を行う必要があり、この場合カルボン酸と等モ
ルの水力堪１注し、この水によりモノハロゲン化カルボ
ン酸が加水分解を受けてグリコール酸となり、反応の進
行が抑制されてしまい低収率となる。また、モノハロゲ
ノアルカンカルボン酸エステルを使用すると前記の欠司
蜀騨消されるが、得られたエステル体をさらに加水分解
する必要力侑り、製造工程が１工程増える。またモノハ
ロゲノアルカンカルボン酸エステルは高価であり、さら
に、人体への襲臘（催涙性）があり、工業的に有利な方
法とは言えない。For example, when a monohalogenated alkanecarboxylic acid is used as an alkylating agent, it is necessary to convert it into an alkali salt in the reaction system and then carry out the reaction. The monohalogenated carboxylic acid undergoes hydrolysis and becomes glycolic acid, which inhibits the progress of the reaction and results in a low yield. Furthermore, when a monohalogenoalkanecarboxylic acid ester is used, the above-mentioned deficiency can be eliminated, but it is necessary to further hydrolyze the obtained ester, which increases the number of manufacturing steps by one step. Moreover, monohalogenoalkanecarboxylic acid esters are expensive, and furthermore, they are offensive to the human body (lachrygenic), and cannot be said to be an industrially advantageous method.
（発明が解決しようとする問題点）
本発明者らは、このような状況に鑑み、従来技術の問題
点を解決すべくフェノキシアルカンカルボン酸誘導体の
製造法について鋭意研究を重ねてきた結果、簡便かつ高
収率で、しかも安全性の高い工業的に有利なフェノキシ
アルカンカルボン酸誘導体の製造法を見出し、本発明を
完成するに至った。(Problems to be Solved by the Invention) In view of the above circumstances, the present inventors have conducted intensive research on a method for producing phenoxyalkane carboxylic acid derivatives in order to solve the problems of the prior art. The present inventors have discovered an industrially advantageous method for producing phenoxyalkane carboxylic acid derivatives with high yield and high safety, and have completed the present invention.
（問題を解決するための手段）
即ち、本発明は
一般式（１）
（式中、Ｒは水素原子またはアルキル基を表す。）で示
されるフェノ−１４ル番体と
一般式（２）
％式％（２）
（式中、Ｍはアルカリ金属を表し、ｎは１〜４の整数を
表す。）
で示されるモノクロロアルカンカルボン酸誘導体をアル
カリ存在下で反応させることを特徴とする一般式（３）
（式中、Ｒおよびｎはいずれも前記の意味を持つ。）
で示されるフェノキシアルカンカルボン酸誘導体の製造
方法をその要旨とするものである。(Means for Solving the Problem) That is, the present invention provides a pheno-14 compound represented by the general formula (1) (wherein R represents a hydrogen atom or an alkyl group) and a general formula (2) % Formula % (2) (wherein M represents an alkali metal, and n represents an integer of 1 to 4) 3) (In the formula, both R and n have the above-mentioned meanings.) The gist thereof is a method for producing a phenoxyalkane carboxylic acid derivative represented by the following formula.
本発明のフェノキシアルカンカルボン酸誘導体を得る基
本の反応は下記式−１によって表さｉ（式中、Ｒ，Ｍお
よびｎ（よいずれも前記の意味を持つ。）
更に詳細に説明すれば、一般式（１）で示されるフェノ
ール誘導体１モルに対して、一般式（２）で示されるモ
ノクロロカルボン酸誘導体１〜５モル、塩基０． ５〜
５モル、溶媒０〜１００モルを加え、０〜１５０°Ｃ１
好ましくは室温〜１００°Ｃの温度に於いて１〜１５時
間、常圧あるいは力ＩＩＦＥ下に反応を行うものである
。The basic reaction for obtaining the phenoxyalkane carboxylic acid derivative of the present invention is represented by the following formula-1: For 1 mol of the phenol derivative represented by formula (1), 1 to 5 mol of the monochlorocarboxylic acid derivative represented by general formula (2) and 0.5 to 5 mol of the base.
Add 5 mol and 0 to 100 mol of solvent, and heat at 0 to 150°C1
Preferably, the reaction is carried out at a temperature of room temperature to 100°C for 1 to 15 hours under normal pressure or force IIFE.
絹已一般式（１）、一般式（３）におけるＲとしては水
素原子；メチル基、エチノり阻プロピノリＦブチル基等
のアルキル基などが挙げられる。Examples of R in the general formula (1) and the general formula (3) include a hydrogen atom; a methyl group, and an alkyl group such as an ethyl-propylene-butyl group.
一般式（２）におけるＭとしてはナトリウム、カリウム
などのアルカリ金属が挙げ６Ｆｒｎは１〜４の整数を表
す。M in the general formula (2) includes alkali metals such as sodium and potassium, and 6Frn represents an integer of 1 to 4.
本発明で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、水酸化マグネシウム水酸化カルシウム
、炭酸ナトリウム、炭酸カリウム、炭酸カルシウム、炭
酸水素ナトリウム、炭酸水素カリウム、酸化カルシウム
、酸化バリウム、水素化すトリウム、ナトリウムエチラ
ートなどの無機塩基；トリエチルアミン、ピリジン、ピ
コリン、ルチジンなどの有機塩基が挙げら瓢好ましくは
水酸化ナトリウム、水酸化カリウムなどのアルカリ金属
の水酸化物が挙げられる。The base used in the present invention includes sodium hydroxide,
Inorganic bases such as potassium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, calcium oxide, barium oxide, thorium hydride, sodium ethylate; triethylamine, pyridine, Examples include organic bases such as picoline and lutidine, and preferably alkali metal hydroxides such as sodium hydroxide and potassium hydroxide.
また、本発明で用いられる）廚菌としては、主ｗ料のフ
ェノール誘導体を溶解し、反応させることのできるもの
であれば良く、例えばメタノール、エタノール、イソプ
ロピルアルコールなどのアルコーノ４、酢酸メチル、酢
酸エチルなどのエステノ１頃、エチルエーテル、テトラ
ヒドロフラン、ジオキサンなどのエーテル類、アセトニ
トリル、ジメチルホルムアミド、ジメチルスルホキシド
ジメチルアセトアミドなどの非プロトン性極性溶媒など
が好ましい。In addition, the bacterium used in the present invention may be one that can dissolve and react the phenol derivative as the main ingredient, such as alcono-4 such as methanol, ethanol, isopropyl alcohol, methyl acetate, acetic acid, etc. Preferred are esters such as ethyl, ethers such as ethyl ether, tetrahydrofuran, and dioxane, and aprotic polar solvents such as acetonitrile, dimethylformamide, and dimethylsulfoxide dimethylacetamide.
（発明の効果）
本発明によれば、工業的に入手可能なモノクロロアルカ
ンカルボン酸アルカリ塩を用いることにより、従来法の
欠へであった水の副生による反応抑制や加水分解工程組
み込みなどの煩雑さを解決し、簡便かつ高収率でフェノ
キシアルカンカルボン酸誘導体を製造することができる
。(Effects of the Invention) According to the present invention, by using an industrially available alkali salt of monochloroalkane carboxylic acid, it is possible to suppress the reaction due to the by-product of water and incorporate the hydrolysis process, which were lacking in conventional methods. Phenoxyalkane carboxylic acid derivatives can be produced easily and in high yields by solving complications.
以下、実施例を挙げて本発明を具体的に説明するが、オ
ニ１ｆｄ１１は本発明を限定するものではない。The present invention will be specifically described below with reference to Examples, but the present invention is not limited to Oni 1fd11.
（実施例１）
２−ヒドロキシ−４−プレニルオキシ−アセトフェノン
ｌ１ｇをアセトニトリル４４ｄに？容解し、これに水酸
化ナトリウム２．４ｇを加え、さらにモノクロル酢酸ソ
ーダ８，７ｇを加えて環流下、３時間反応させた。反応
終了後論却下希塩酸を加え、析出した結晶をろ過し粗結
晶を得た。この粗結晶を酢酸エチルで再結晶し、白色の
結晶２−（カルボキシメチルオキシ）−４−プレニルオ
キシアセトフェノン１１．８ｇ（収率８５％）を得た。(Example 1) 1 g of 2-hydroxy-4-prenyloxy-acetophenone to 44 d of acetonitrile? The mixture was dissolved, and 2.4 g of sodium hydroxide was added thereto, followed by 8.7 g of sodium monochloroacetate, and the mixture was reacted under reflux for 3 hours. After the reaction was over, dilute hydrochloric acid was added, and the precipitated crystals were filtered to obtain crude crystals. The crude crystals were recrystallized from ethyl acetate to obtain 11.8 g (yield: 85%) of white crystals of 2-(carboxymethyloxy)-4-prenyloxyacetophenone.
融点：１２５〜１２６’Ｃ
（比較例）
実施例１においてモノクロル酢酸ソーダのかわりにモノ
クロ）Ｌ４ｍｍを用いて同様の処理を行ったところ２−
（カルボキシメチルオキシ）−４−プレニルオキシ−ア
セトフェノンは５．８ｇ（収率４２％）であった。Melting point: 125-126'C (Comparative example) When the same treatment as in Example 1 was performed using monochrome (monochrome) L4 mm instead of monochlorosodium acetate, 2-
(Carboxymethyloxy)-4-prenyloxy-acetophenone was 5.8 g (yield 42%).
（実施例２）
２−ヒドロキシ−４−プレニルオキシ−アセトフェノン
ｌ１ｇをアセトニトリル４４ｍ１に溶解し、これにｍヒ
カリウム３．５ｇを加え、さらにモノクロロ酢酸ソーダ
７．０ｇを加えて攪拌下、８０°Ｃで３時間反応させた
。反応終了冷却上希塩酸（カルボキシメチルオキシ）−
４−プレニルオキシ−アセトフェノン７．１ｇ（収率７
０％）を得た。(Example 2) 1 g of 2-hydroxy-4-prenyloxy-acetophenone was dissolved in 44 ml of acetonitrile, 3.5 g of m-hypotassium was added thereto, and further 7.0 g of sodium monochloroacetate was added, and the mixture was heated at 80°C with stirring. The reaction was allowed to proceed for 3 hours. After completion of reaction, cool dilute hydrochloric acid (carboxymethyloxy)-
7.1 g of 4-prenyloxy-acetophenone (yield: 7
0%) was obtained.
融点 １２５〜１２６℃Melting point: 125-126℃
Claims (2)
されるフェノール誘導体と 一般式（２） Ｃｌ（ＣＨ＿２）＿ｎＣＯＯＭ（２） （式中、Ｍはアルカリ金属を表し、ｎは１〜４の整数を
表す。） で示されるモノクロロアルカンカルボン酸誘導体をアル
カリ存在下で反応させることを特徴とする一般式（３） ▲数式、化学式、表等があります▼（３） （式中、Ｒ、およびｎはいずれも前記の意味を持つ。） で示されるフェノキシアルカンカルボン酸誘導体の製造
方法。(1) General formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (1) (In the formula, R represents a hydrogen atom or an alkyl group.) Phenol derivatives and general formula (2) Cl (CH_2 )_nCOOM(2) (In the formula, M represents an alkali metal, and n represents an integer of 1 to 4.) General formula (2) characterized by reacting a monochloroalkane carboxylic acid derivative represented by 3) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(3) (In the formula, R and n both have the above meanings.) A method for producing a phenoxyalkane carboxylic acid derivative represented by the following.
ある請求項（１）記載の製造方法。(2) The manufacturing method according to claim (1), wherein the compound of general formula (2) is sodium monochloroacetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2106388A JPH0825953B2 (en) | 1990-04-24 | 1990-04-24 | Method for producing phenoxyalkanecarboxylic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2106388A JPH0825953B2 (en) | 1990-04-24 | 1990-04-24 | Method for producing phenoxyalkanecarboxylic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH045255A true JPH045255A (en) | 1992-01-09 |
| JPH0825953B2 JPH0825953B2 (en) | 1996-03-13 |
Family
ID=14432319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2106388A Expired - Lifetime JPH0825953B2 (en) | 1990-04-24 | 1990-04-24 | Method for producing phenoxyalkanecarboxylic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0825953B2 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS53116355A (en) * | 1977-03-18 | 1978-10-11 | Taisho Pharmaceut Co Ltd | Chalcone derivatives |
| JPS5888340A (en) * | 1981-11-19 | 1983-05-26 | Dainippon Ink & Chem Inc | Preparation of phenoxycarboxylic acid derivative |
| JPS58105935A (en) * | 1981-12-18 | 1983-06-24 | Dainippon Ink & Chem Inc | Preparation of phenoxy compound derivative |
| JPS58126833A (en) * | 1982-01-25 | 1983-07-28 | Dainippon Ink & Chem Inc | Preparation of phenoxycarboxylic acid derivative |
| JPS6216446A (en) * | 1984-10-26 | 1987-01-24 | Nissan Chem Ind Ltd | Production of optically active 2-(4-hydroxyphenoxy) propionic acid |
-
1990
- 1990-04-24 JP JP2106388A patent/JPH0825953B2/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS53116355A (en) * | 1977-03-18 | 1978-10-11 | Taisho Pharmaceut Co Ltd | Chalcone derivatives |
| JPS5888340A (en) * | 1981-11-19 | 1983-05-26 | Dainippon Ink & Chem Inc | Preparation of phenoxycarboxylic acid derivative |
| JPS58105935A (en) * | 1981-12-18 | 1983-06-24 | Dainippon Ink & Chem Inc | Preparation of phenoxy compound derivative |
| JPS58126833A (en) * | 1982-01-25 | 1983-07-28 | Dainippon Ink & Chem Inc | Preparation of phenoxycarboxylic acid derivative |
| JPS6216446A (en) * | 1984-10-26 | 1987-01-24 | Nissan Chem Ind Ltd | Production of optically active 2-(4-hydroxyphenoxy) propionic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0825953B2 (en) | 1996-03-13 |
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