JPH0150708B2 - - Google Patents
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- Publication number
- JPH0150708B2 JPH0150708B2 JP56157955A JP15795581A JPH0150708B2 JP H0150708 B2 JPH0150708 B2 JP H0150708B2 JP 56157955 A JP56157955 A JP 56157955A JP 15795581 A JP15795581 A JP 15795581A JP H0150708 B2 JPH0150708 B2 JP H0150708B2
- Authority
- JP
- Japan
- Prior art keywords
- phenoxazine
- pyrido
- oxo
- hydroxy
- sodium
- 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
Links
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Description
【発明の詳細な説明】
本発明は下記一般式
〔式中、Ｒは水素原子、カルボキシル基、アセチ
ル基または−CONHCH2COOHを示す。〕で表わ
される１−ヒドロキシ−５−オキソ−5H−ピリ
ド〔３，２−ａ〕フエノキサジン−３−カルボン
酸類の精製法に関する。[Detailed Description of the Invention] The present invention is based on the following general formula [In the formula, R represents a hydrogen atom, a carboxyl group, an acetyl group, or -CONHCH 2 COOH. This invention relates to a method for purifying 1-hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acids represented by
１−ヒドロキシ−５−オキソ−5H−ピリド
〔３，２−ａ〕フエノキサジン−３−カルボン酸
は、白内障の治療剤として用いられている。しか
し、１−ヒドロキシ−５−オキソ−5H−ピリド
〔３，２−ａ〕フエノキサジン−３−カルボン酸
類（以下、ピリドフエノキサジン化合物と略す。）
は、非常に精製しにくい化合物で、再結晶法等の
簡単な精製法では満足すべき純度の結晶を得るこ
とはできない為、工業的に有利な精製法の開発が
持たれている。 1-Hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acid is used as a therapeutic agent for cataracts. However, 1-hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acids (hereinafter abbreviated as pyridophenoxazine compounds)
is a compound that is extremely difficult to purify, and because crystals of satisfactory purity cannot be obtained using simple purification methods such as recrystallization, an industrially advantageous purification method is being developed.
ピリドフエノキサジン化合物の精製法として、
カリウムイオンの存在下、次亜塩素酸塩を作用さ
せる方法（特開昭51−11800）が開示されている。
しかしながら、ピリドフエノキサジン化合物は強
力な酸化剤のもとでは分解しやすく、次亜塩素酸
塩の様な強力な酸化剤を作用させて精製する方法
は工業的に有利とは言えない。又、上記方法はカ
リウムイオンの存在下でないと満足すべき純度の
結晶が得られないという欠点がある。本発明者ら
は、ピリドフエノキサジン化合物の精製法を種々
検討した結果、陽極酸化する事により従来の精製
法の欠点が一挙に解決できる事を見い出し本発明
を完成した。陽極酸化が有利な理由としては、毒
性の強い酸化剤を使用しない事、酸化条件が緩和
な事、得られる精製品の純度が良い事および工業
的に安価な方法である事等が挙げられる。 As a method for purifying pyridophenoxazine compounds,
A method is disclosed in which hypochlorite is applied in the presence of potassium ions (Japanese Patent Application Laid-Open No. 11800/1983).
However, pyridophenoxazine compounds are easily decomposed in the presence of strong oxidizing agents, and purification methods using strong oxidizing agents such as hypochlorite cannot be said to be industrially advantageous. Furthermore, the above method has the disadvantage that crystals of satisfactory purity cannot be obtained unless in the presence of potassium ions. The present inventors investigated various methods for purifying pyridophenoxazine compounds, and as a result, discovered that the drawbacks of conventional purification methods could be solved at once by anodic oxidation, and completed the present invention. Reasons why anodic oxidation is advantageous include the fact that highly toxic oxidizing agents are not used, the oxidation conditions are mild, the purified product obtained has good purity, and it is an industrially inexpensive method.
本発明をさらに詳しく説明すると、本発明は粗
製ピリドフエノキサジン化合物のアルカリ金属塩
を通常の電解槽中で陽極酸化し、得られる精製ピ
リドフエノキサジン化合物の塩類を、通常の酸処
理によつて精製ピリドフエノキサジン化合物を得
ることにある。電解槽の陽極側と陰極側はイオン
交換膜などの隔膜で隔てられているのが好まし
く、電極としては白金、白金黒、酸化鉛、銀、炭
素、グラフアイト等を用いることができる。又、
電解液は機械的に撹拌することが好ましい。電
圧、電流密度または温度にはとくに制限はない
が、好ましくは電圧として１〜20V、電流密度と
して0.01〜10A／ｄm2、又温度は室温が用いられ
る。電解質としては、水酸化ナトリウム、酢酸ナ
トリウム、リン酸一水素ナトリウム、リン酸二水
素ナトリウム、炭酸ナトリウム、塩化ナトリウム
および硫酸ナトリウム等の通常用いられるもので
よい。 To explain the present invention in more detail, the present invention involves anodizing an alkali metal salt of a crude pyridophenoxazine compound in a conventional electrolytic bath, and treating the resulting purified salts of a pyridophenoxazine compound with a conventional acid. The purpose is to obtain a purified pyridophenoxazine compound. The anode side and cathode side of the electrolytic cell are preferably separated by a diaphragm such as an ion exchange membrane, and platinum, platinum black, lead oxide, silver, carbon, graphite, etc. can be used as the electrode. or,
Preferably, the electrolyte is mechanically stirred. Although there are no particular limitations on the voltage, current density or temperature, preferably the voltage is 1 to 20 V, the current density is 0.01 to 10 A/dm 2 , and the temperature is room temperature. As the electrolyte, commonly used ones such as sodium hydroxide, sodium acetate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, sodium carbonate, sodium chloride, and sodium sulfate may be used.
以下に実施例を示す。 Examples are shown below.
実施例 １
粗製１−ヒドロキシ−５−オキソ−5H−ピリ
ド〔３，２−ａ〕フエノキサジン−３−カルボン
酸（1.0ｇ）を１％リン酸一水素ナトリウム、水
溶液（250ml）に溶解後不溶物を過し、液を
陽極液とする。陰極液として１％リン酸一水素ナ
トリウム水溶液を用いる。両極液は陽イオン交換
膜で隔てられ、陽極として炭素板、陰極として銀
板を用いる。両極液を撹拌しながら、直流電圧６
〜12V、電流密度0.6〜0.8A／ｄm2の条件下、室
温で10分間電解する。Example 1 After dissolving crude 1-hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acid (1.0 g) in 1% sodium monohydrogen phosphate, aqueous solution (250 ml), the insoluble matter was removed. The solution is used as an anolyte. A 1% aqueous sodium monohydrogen phosphate solution is used as the catholyte. Both electrolytes are separated by a cation exchange membrane, and a carbon plate is used as an anode and a silver plate is used as a cathode. While stirring the bipolar liquid, apply a DC voltage of 6
Electrolyze for 10 minutes at room temperature under conditions of ~12V and current density of 0.6-0.8A/ dm2 .
電解終了後陽極液を取り出し、15％リン酸二水
素ナトリウム、（10ml）を加え、冷蔵庫に一夜静
置する。沈殿するカリウム塩を遠沈する。沈殿物
に2N塩酸を加えよく撹拌した後遠沈する。沈殿
物を水で３回洗つた後１％リン酸二水素ナトリウ
ム水溶液に溶解する。この溶液を2N塩酸で酸性
とし得られる沈殿物を遠沈する。沈殿物を水で洗
浄後乾燥し、精製１−ヒドロキシ−５−オキソ−
5H−ピリド〔３，２−ａ〕フエノキサジン−３
−カルボン酸0.8ｇ（収率80％）を得る。 After electrolysis is complete, remove the anolyte, add 15% sodium dihydrogen phosphate (10 ml), and leave it in the refrigerator overnight. Centrifuge the precipitated potassium salt. Add 2N hydrochloric acid to the precipitate, stir well, and then centrifuge. The precipitate was washed three times with water and then dissolved in a 1% aqueous sodium dihydrogen phosphate solution. This solution is acidified with 2N hydrochloric acid and the resulting precipitate is centrifuged. The precipitate was washed with water and dried to obtain purified 1-hydroxy-5-oxo-
5H-pyrido[3,2-a]phenoxazine-3
- Obtain 0.8 g (80% yield) of carboxylic acid.
融点248〜249℃（分解）
IR（KBr、cm-1） 1700、1635、1576
UVmax（リン酸緩衝液（PH7.0））
230nm（ε＝33000）、433nm（ε＝18800）
実施例 ２
粗製１−ヒドロキシ−５−オキソ−5H−ピリ
ド〔３，２−ａ〕フエノキサジン−３−カルボン
酸（1.0ｇ）を１％リン酸一水素ナトリウム水溶
液（200ml）に溶解後不溶物を過し、液に１
％食塩水（50ml）を加えて陽極液とする。陰極液
としては１％食塩水を用いる。以下実施例１と同
条件で電解する。電解終了後陽極液を取り出し、
2N塩酸を加え酸性とし、沈殿物を遠沈する。沈
殿物を水洗後１％リン酸一水素ナトリウムに溶解
し、15％リン酸二水素カリウムを加え冷蔵庫に一
夜静置する。沈殿するカリウム塩を遠沈する。以
下実施例１と同様に操作して、精製１−ヒドロキ
シ−５−オキソ−5H−ピリド〔３，２−ａ〕フ
エノキサジン−３−カルボン酸0.72ｇ（収率72
％）を得る。 Melting point 248-249℃ (decomposed) IR (KBr, cm -1 ) 1700, 1635, 1576 UVmax (phosphate buffer (PH7.0)) 230nm (ε=33000), 433nm (ε=18800) Example 2 Crude 1-Hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acid (1.0 g) was dissolved in a 1% aqueous sodium monohydrogen phosphate solution (200 ml), and the insoluble matter was filtered off. to 1
Add % saline solution (50ml) to make the anolyte. 1% saline is used as the catholyte. Electrolysis is carried out under the same conditions as in Example 1. After electrolysis, remove the anolyte and
Add 2N hydrochloric acid to make acidic and centrifuge the precipitate. After washing the precipitate with water, dissolve it in 1% sodium monohydrogen phosphate, add 15% potassium dihydrogen phosphate, and leave it in the refrigerator overnight. Centrifuge the precipitated potassium salt. Thereafter, the same procedure as in Example 1 was carried out to obtain 0.72 g of purified 1-hydroxy-5-oxo-5H-pyrido[3,2-a]phenoxazine-3-carboxylic acid (yield: 72
%).
物性は実施例１で得られた結晶と同じ。 The physical properties are the same as those of the crystal obtained in Example 1.
Claims (1)
ル基または−CONHCH2COOHを示す。〕で表わ
される化合物を陽極酸化する事を特徴とする１−
ヒドロキシ−５−オキソ−5H−ピリド〔３，２
−ａ〕フエノキサジン−３−カルボン酸類の精製
法。[Claims] 1. The following general formula [In the formula, R represents a hydrogen atom, a carboxyl group, an acetyl group, or -CONHCH 2 COOH. 1-, which is characterized by anodic oxidation of a compound represented by
Hydroxy-5-oxo-5H-pyrido [3,2
-a] Purification method of phenoxazine-3-carboxylic acids.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56157955A JPS5859989A (en) | 1981-10-02 | 1981-10-02 | Purifying method of pyridophenoxazine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56157955A JPS5859989A (en) | 1981-10-02 | 1981-10-02 | Purifying method of pyridophenoxazine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5859989A JPS5859989A (en) | 1983-04-09 |
| JPH0150708B2 true JPH0150708B2 (en) | 1989-10-31 |
Family
ID=15661107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56157955A Granted JPS5859989A (en) | 1981-10-02 | 1981-10-02 | Purifying method of pyridophenoxazine compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5859989A (en) |
-
1981
- 1981-10-02 JP JP56157955A patent/JPS5859989A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5859989A (en) | 1983-04-09 |
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