JP2514072B2 - Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid - Google Patents
Process for producing optically active 2- (4-hydroxyphenoxy) propionic acidInfo
- Publication number
- JP2514072B2 JP2514072B2 JP63181285A JP18128588A JP2514072B2 JP 2514072 B2 JP2514072 B2 JP 2514072B2 JP 63181285 A JP63181285 A JP 63181285A JP 18128588 A JP18128588 A JP 18128588A JP 2514072 B2 JP2514072 B2 JP 2514072B2
- Authority
- JP
- Japan
- Prior art keywords
- propionic acid
- hydroxyphenoxy
- optically active
- hydroquinone
- 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.)
- Expired - Lifetime
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は、高純度の光学活性２−（４−ヒドロキシフ
ェノキシ）プロピオン酸の製造に関するものである。TECHNICAL FIELD The present invention relates to the production of highly pure optically active 2- (4-hydroxyphenoxy) propionic acid.
本発明の方法で得られる化合物は各種フェノキシプロ
ピオン酸系除草剤の合成中間体として有用である。The compound obtained by the method of the present invention is useful as a synthetic intermediate for various phenoxypropionic acid herbicides.
（従来の技術及び発明が解決しようとする課題） ２−（４−ヒドロキシフェノキシ）プロピオン酸のラ
セミ体または光学活性体の製法としては、ハイドロキノ
ンと対応するプロピオン酸誘導体との反応により目的物
を得る方法が一般的であり、公知例としては例えば、特
開昭56-59718号、特開昭58-183666号、特開昭59-95237
号、特開昭60-94935号、特開昭60-209548号、特開昭61-
109753号、特開昭61-158947号等を挙げることが出来
る。(Problems to be Solved by Conventional Techniques and Inventions) As a method for producing a racemic form or an optically active form of 2- (4-hydroxyphenoxy) propionic acid, a target product is obtained by reacting hydroquinone with a corresponding propionic acid derivative. The method is general, and known examples include, for example, JP-A-56-59718, JP-A-58-183666, and JP-A-59-95237.
No. 60-94935, 60-209548, 61-61
109753, JP-A-61-158947 and the like can be mentioned.
これらの方法では目的のハイドロキノンモノ置換体の
外に不要なビス置換体の副生を伴うという問題点があ
る。These methods have a problem that in addition to the desired hydroquinone mono-substituted product, unnecessary bis-substituted products are produced as by-products.
モノ置換体を選択的に得るための試みも幾つか知られ
ている（例えば、特開昭59-231044号、アメリカ特許436
8068号、特表昭57-501178号、特開昭60-81150号）。Some attempts to selectively obtain mono-substituted products have been known (for example, JP-A-59-231044 and US Pat. No. 436).
8068, Tokushusho 57-501178, and JP-A-60-81150).
これらの方法はいずれも形式的にはハイドロキノンの
一方を保護した上でプロピオン酸誘導体と反応させた後
に保護基を除去するという方式を採用しているため、保
護基の導入及び除去といった繁雑な工程を経なければな
らない。また、目的物が光学活性体の場合には、いずれ
の方法においても、光学純度は必ずしも満足のいくもの
ではなく、光学的に高純度な化合物を得ようとすれば、
例えば、特開昭61-83144号のごとく、ジアステレオマー
法による光学分割操作を何度か繰り返す必要があった。All of these methods formally employ a method in which one side of hydroquinone is protected and then reacted with a propionic acid derivative, and then the protecting group is removed, so that complicated steps such as introduction and removal of the protecting group are carried out. Have to go through. Further, when the target product is an optically active substance, in any method, the optical purity is not always satisfactory, and if an optically highly pure compound is to be obtained,
For example, as in JP-A-61-83144, it was necessary to repeat the optical division operation by the diastereomer method several times.
また、従来の方法に於いては、反応溶媒に注意を払う
必要があった。即ち、用いられる原料ハイドロキノン及
びその金属塩は水溶性であるが、対応するプロピオン酸
誘導体の水に対する溶解度は必ずしも高くないことが多
く、さらに、水溶液中では不安定なことが多いため、速
やかに反応させることが必要であった。そのため、種々
の溶媒が用いられてきたが、目的物の単離にはかえって
繁雑な抽出等の操作を必要とした。また、溶媒としての
水の使用量を制限した場合には、原料ハイドロキノン及
びその金属塩或いは生成物が反応中析出して反応系が不
均一になるため、十分な攪拌が行えず、反応効率が低下
するため、水に対して不安定な原料のプロピオン酸誘導
体が分解して収率が低下する問題があった。Moreover, in the conventional method, it was necessary to pay attention to the reaction solvent. That is, although the starting material hydroquinone and its metal salt used are water-soluble, the solubility of the corresponding propionic acid derivative in water is often not always high, and further, in many cases it is unstable in an aqueous solution, so that a rapid reaction occurs. It was necessary to let them do. For this reason, various solvents have been used, but isolation of the target product requires rather complicated operations such as extraction. When the amount of water used as the solvent is limited, the starting material hydroquinone and its metal salt or product are precipitated during the reaction and the reaction system becomes non-uniform, so that sufficient stirring cannot be performed and the reaction efficiency is increased. Therefore, there is a problem that the propionic acid derivative, which is a raw material unstable to water, is decomposed and the yield is decreased.
一方、均一系、例えば溶媒に充分な量の水を用いて反
応させた場合には、反応は速やかに進行しうるが、従来
は、反応後有機溶媒、例えばメチルイソブチルケトンに
よって生成物を抽出して取り出す方法が行われていた
（特開昭59-95237号）。しかし、この場合には目的以外
の成分も同時に抽出されるため、再精製が必要であり、
工業的には操作上、装置上のいずれにおいても不利であ
った。On the other hand, when the reaction is carried out in a homogeneous system, for example, using a sufficient amount of water as a solvent, the reaction can proceed rapidly, but conventionally, after the reaction, the product is extracted with an organic solvent, for example, methyl isobutyl ketone. The method of taking it out was used (Japanese Patent Laid-Open No. 59-95237). However, in this case, since components other than the target are extracted at the same time, repurification is required,
It is industrially disadvantageous in terms of operation and equipment.
以上の様に、従来技術においては工業的有利に化学的
及び光学的に高純度な２−（４−ヒドロキシフェノキ
シ）プロピオン酸を得ることは困難であった。As described above, it has been difficult in the prior art to obtain 2- (4-hydroxyphenoxy) propionic acid which is industrially advantageous and highly pure chemically and optically.
本発明は溶媒に充分な量の水を用いた場合の製法に着
目し、特にその効率的な精製法を提供することを目的と
するものである。The present invention focuses on a production method in which a sufficient amount of water is used as a solvent, and an object thereof is to provide an efficient purification method thereof.
（課題を解決するための手段） 即ち、本発明はハイドロキノンを原料とする光学活性
２−（４−ヒドロキシフェノキシ）プロピオン酸の製造
において、ハイドロキノンのアルカリ金属塩と２−（４
−ヒドロキシフェノキシ）プロピオン酸のアルカリ金属
塩を含む反応粗液からハイドロキノン及び２−（４−ヒ
ドロキシフェノキシ）プロピオン酸を、逐次、結晶化さ
せることを特徴とする光学活性２−（４−ヒドロキシフ
ェノキシ）プロピオン酸の製法に関するものである。(Means for Solving the Problem) That is, in the present invention, in the production of optically active 2- (4-hydroxyphenoxy) propionic acid using hydroquinone as a raw material, an alkali metal salt of hydroquinone and 2- (4
-Hydroxyphenoxy) propionic acid-containing optically active 2- (4-hydroxyphenoxy), characterized in that hydroquinone and 2- (4-hydroxyphenoxy) propionic acid are sequentially crystallized from a reaction crude liquid containing the alkali metal salt. The present invention relates to a method for producing propionic acid.
本発明の反応粗液は、ハイドロキノンと光学活性プロ
ピオン酸誘導体とを反応させて得られるものである。こ
こで光学活性プロピオン酸誘導体としては、２−クロロ
プロピオン酸、２−ブロモプロピオン酸、２−トシルオ
キシプロピオン酸、２−メシルオキシプロピオン酸等の
カルボン酸あるいはこれらのエステル類が挙げられ、そ
の鏡像体過剰率は以下なるものでもよいが、好ましくは
50％e.e.以上のものが用いられる。The reaction crude liquid of the present invention is obtained by reacting hydroquinone with an optically active propionic acid derivative. Examples of the optically active propionic acid derivative include carboxylic acids such as 2-chloropropionic acid, 2-bromopropionic acid, 2-tosyloxypropionic acid, and 2-mesyloxypropionic acid, or esters thereof, and their mirror images. The excess ratio may be the following, but preferably
Those with 50% ee or more are used.
反応を行うに当たっては、通常、原料のハイドロキノ
ンと光学活性プロピオン酸誘導体は、夫々、水酸化ナト
リウム、水酸化カリウム等の水性アルカリ溶液として供
される。なお、光学活性プロピオン酸あるいはハイドロ
キノンをそれらのアルカリ金属塩として供することもで
きる。In carrying out the reaction, the raw material hydroquinone and the optically active propionic acid derivative are usually provided as an aqueous alkaline solution of sodium hydroxide, potassium hydroxide or the like, respectively. In addition, optically active propionic acid or hydroquinone can be provided as their alkali metal salts.
反応溶媒は、好ましくは水であるが、結晶化を妨げな
い範囲の量の有機溶媒を含むことは差し支えない。ま
た、用いられる水の量は好ましくは反応中及び反応終了
時、反応粗液がほぼ均一になる量である。The reaction solvent is preferably water, but it is acceptable to include an organic solvent in an amount within the range that does not prevent crystallization. The amount of water used is preferably such that the reaction crude liquid becomes substantially uniform during the reaction and at the end of the reaction.
反応に使用される原料ハイドロキノンと光学活性プロ
ピオン酸誘導体のモル比は、前述のビス置換体の生成を
抑制するためハイドロキノンを過剰量用いることがが望
ましく、好ましくは1.1〜3.0、さらに好ましくは1.2〜
2.4である。従って、反応終了後未反応および過剰のハ
イドロキノンを回収することが経済的には必要である。The molar ratio of the raw material hydroquinone used in the reaction to the optically active propionic acid derivative is preferably an excessive amount of hydroquinone in order to suppress the formation of the above-mentioned bis-substituted product, preferably 1.1 to 3.0, more preferably 1.2 to
It is 2.4. Therefore, it is economically necessary to recover unreacted and excess hydroquinone after completion of the reaction.
本発明の方法を工程を追って説明すると、上記に例示
した反応粗液は均一で、未反応ハイドロキノンは遊離、
あるいはアルカリ金属塩として溶解しており、生成した
２−（４−ヒドロキシフェノキシ）プロピオン酸はアル
カリ金属塩として溶解している。Explaining the method of the present invention step by step, the reaction crude liquid exemplified above is uniform, unreacted hydroquinone is released,
Alternatively, it is dissolved as an alkali metal salt, and the produced 2- (4-hydroxyphenoxy) propionic acid is dissolved as an alkali metal salt.
反応終了後、０℃〜室温に冷却する。次に、この反応
粗液からハイドロキノン及び２−（４−ヒドロキシフェ
ノキシ）プロピオン酸を夫々析出させるために、反応液
を両者が同時に析出するpH値の領域よりも高いpH値、例
えば７付近に調整すると、まずハイドロキノンが析出す
る。これを別した後、液をさらにより低いpH、例え
ばpH1付近に調整し冷却すると、目的の光学活性２−
（４−ヒドロキシフェノキシ）プロピオン酸が析出す
る。これを別すると高純度の光学活性２−（４−ヒド
ロキシフェノキシ）プロピオン酸が得られる。After completion of the reaction, the mixture is cooled to 0 ° C to room temperature. Next, in order to precipitate hydroquinone and 2- (4-hydroxyphenoxy) propionic acid from this reaction crude liquid, respectively, the reaction liquid was adjusted to a pH value higher than the pH value region in which both precipitate at the same time, for example, around 7. Then, hydroquinone is first deposited. After separating this, the liquid is adjusted to a lower pH, for example, around pH 1, and cooled to obtain the desired optical activity 2-
(4-Hydroxyphenoxy) propionic acid precipitates. Except for this, highly pure optically active 2- (4-hydroxyphenoxy) propionic acid is obtained.
（発明の効果） 本発明の方法により、プロピオン酸系除草剤の中間体
である２−（４−ヒドロキシフェノキシ）プロピオン酸
を化学的及び光学的に高い純度で簡便に単離でき、未反
応のハイドロキノンも簡単に回収することができる。(Effect of the Invention) By the method of the present invention, 2- (4-hydroxyphenoxy) propionic acid, which is an intermediate of a propionic acid-based herbicide, can be easily isolated with high purity chemically and optically, and unreacted. Hydroquinone can also be easily recovered.
また、水を溶媒として反応する場合に問題となる不均
一系反応による収率低下を避けうる量の水を用いて均一
系での反応を行なうことにより得られる反応粗液に好適
に適用できるため、製造装置上及び原材料費上の経費負
担を大巾に軽減することが可能となった。Further, since it can be suitably applied to a reaction crude liquid obtained by carrying out a reaction in a homogeneous system by using an amount of water that can avoid a yield reduction due to a heterogeneous reaction which becomes a problem when reacting with water as a solvent. , It became possible to significantly reduce the cost burden on the manufacturing equipment and raw material costs.
（実施例） 以下、実施例を用いて本発明を詳述する。(Example) Hereinafter, the present invention will be described in detail with reference to Examples.
実施例１ （Ｓ）−２−クロロプロピオン酸メチル（光学純度9
5.5％）123部を25％水酸化ナトリウム水溶液160部と混
合し、（Ｓ）−２−クロロプロピオン酸ナトリウム塩の
水溶液を得る。これをハイドロキノン220部と25％水酸
化ナトリウム水溶液640部を混合した均一溶液に80℃で
滴下して反応させる。Example 1 Methyl (S) -2-chloropropionate (optical purity 9
5.5%) 123 parts are mixed with 160 parts of 25% aqueous sodium hydroxide solution to obtain an aqueous solution of (S) -2-chloropropionic acid sodium salt. Hydroquinone (220 parts) and a 25% aqueous sodium hydroxide solution (640 parts) are added dropwise to a uniform solution at 80 ° C to react.
反応終了後、反応液を５℃に冷却し、33％塩酸水でpH
7に調整し、ハイドロキノンを析出させる。これを別
して得られた回収ハイドロキノンは高純度で、回収率は
72.3％であった。After the reaction is complete, cool the reaction mixture to 5 ° C and adjust the pH with 33% aqueous hydrochloric acid.
Adjust to 7 to precipitate hydroquinone. The recovered hydroquinone obtained by separating this is of high purity, and the recovery rate is
It was 72.3%.
次いで、液を５℃に冷却したままpH1に調整する
と、（Ｒ）−２−（４−ヒドロキシフェノキシ）プロピ
オン酸が析出する。これを別して得られた結晶（Ｒ）
−２−（４−ヒドロキシフェノキシ）プロピオン酸は18
4部（収率84.7％，光学純度98.4％）であった。Then, the liquid is adjusted to pH 1 while being cooled to 5 ° C., whereby (R) -2- (4-hydroxyphenoxy) propionic acid is precipitated. Crystal (R) obtained by separating this
-2- (4-hydroxyphenoxy) propionic acid is 18
It was 4 parts (yield 84.7%, optical purity 98.4%).
尚、このときの液中の（Ｒ）−２−（４−ヒドロキ
シフェノキシ）プロピオン酸の光学純度は80％であっ
た。The optical purity of (R) -2- (4-hydroxyphenoxy) propionic acid in the liquid at this time was 80%.
前記の結晶はそのまま製品になりうるが、さらに水か
ら再結晶した結果、化学純度、光学純度ともほぼ100％
の（Ｒ）−２−（４−ヒドロキシフェノキシ）プロピオ
ン酸が得られた。The above crystals can be used as they are, but as a result of being recrystallized from water, the chemical purity and optical purity are almost 100%.
(R) -2- (4-hydroxyphenoxy) propionic acid was obtained.
Claims (1)
ノンとを反応させて光学活性２−（４−ヒドロキシフェ
ノキシ）プロピオン酸を製造するにおいて、反応粗液を
冷却後、ハイドロキノンが結晶化する程度にpHを下げ、
析出別後、液のpHを更に下げ、光学活性２−（４−
ヒドロキシフェノキシ）プロピオン酸を結晶化させ、
別させることを特徴とする、光学活性２−（４−ヒドロ
キシフェノキシ）プロピオン酸の製法。1. When an optically active 2- (4-hydroxyphenoxy) propionic acid is produced by reacting an optically active propionic acid derivative with hydroquinone, after the reaction crude liquid is cooled, the pH is adjusted to such an extent that hydroquinone is crystallized. Lower
After precipitation, the pH of the solution was further lowered to obtain optically active 2- (4-
(Hydroxyphenoxy) propionic acid is crystallized,
A method for producing optically active 2- (4-hydroxyphenoxy) propionic acid, which is characterized by differentiating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63181285A JP2514072B2 (en) | 1988-07-20 | 1988-07-20 | Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63181285A JP2514072B2 (en) | 1988-07-20 | 1988-07-20 | Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0232039A JPH0232039A (en) | 1990-02-01 |
| JP2514072B2 true JP2514072B2 (en) | 1996-07-10 |
Family
ID=16098019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63181285A Expired - Lifetime JP2514072B2 (en) | 1988-07-20 | 1988-07-20 | Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2514072B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0322917D0 (en) * | 2003-09-30 | 2003-11-05 | Syngenta Ltd | Chemical process |
| CN116355969B (en) * | 2023-05-23 | 2023-12-15 | 锦州四海生物化学有限公司 | Method for biosynthesis of R- (+) -2- (4-hydroxyphenoxy) propionic acid |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0610154B2 (en) * | 1984-12-28 | 1994-02-09 | 日産化学工業株式会社 | Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid |
-
1988
- 1988-07-20 JP JP63181285A patent/JP2514072B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0232039A (en) | 1990-02-01 |
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