JPH07145170A - Production of quinolonecarboxylic acids - Google Patents
Production of quinolonecarboxylic acidsInfo
- Publication number
- JPH07145170A JPH07145170A JP29202993A JP29202993A JPH07145170A JP H07145170 A JPH07145170 A JP H07145170A JP 29202993 A JP29202993 A JP 29202993A JP 29202993 A JP29202993 A JP 29202993A JP H07145170 A JPH07145170 A JP H07145170A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- quinolonecarboxylic
- alkali metal
- salt
- aqueous solution
- 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
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、キノロンカルボン酸類
アルカリ金属塩からキノロンカルボン酸類を製造する方
法に関する。キノロンカルボン酸類は医薬あるいは農薬
として有用な化合物である。FIELD OF THE INVENTION The present invention relates to a method for producing quinolonecarboxylic acids from quinolonecarboxylic acid alkali metal salts. Quinolonecarboxylic acids are compounds useful as medicines or agricultural chemicals.
【０００２】[0002]
【従来の技術】キノロンカルボン酸類アルカリ金属塩水
溶液に酸を作用させてキノロンカルボン酸類を得ること
は特公昭51-18440号、特公昭42-5666 号に記載されてい
る。2. Description of the Related Art It is described in JP-B-51-18440 and JP-B-42-5666 that an acid is allowed to act on an aqueous solution of an alkali metal quinolone carboxylic acid to obtain a quinolone carboxylic acid.
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、従来の
キノロンカルボン酸類アルカリ金属塩水溶液に酸を加
え、酸性としてキノロンカルボン酸類を充分析出させる
方法では、不純物も同時に析出するため、得られるキノ
ロンカルボン酸類の純度が低いこと、また得られるキノ
ロンカルボン酸類の粒度が小さいため濾過性が極めて悪
いこと等、工業的に実施するには問題点を有していた。However, in the conventional method of adding an acid to an aqueous solution of an alkali metal salt of a quinolonecarboxylic acid to acidify it to sufficiently precipitate the quinolonecarboxylic acid, impurities are also precipitated at the same time. There are problems in industrial implementation such as low purity and extremely poor filterability due to the small particle size of the obtained quinolonecarboxylic acids.
【０００４】[0004]
【課題を解決するための手段】本発明者らは上記問題点
を解決するため鋭意検討した結果、反応液の最終ｐＨを
６．０〜８．５に制御することにより、収率を下げるこ
となく不純物の析出量を少なくすることができること、
またキノロンカルボン酸類アルカリ金属塩水溶液と酸水
溶液とを同時に併注することによって粒度が大きく、濾
過性の良好なキノロンカルボン酸類が得られることを見
いだし、本発明を完成するに至った。Means for Solving the Problems As a result of intensive studies for solving the above-mentioned problems, the present inventors have found that the final pH of the reaction solution is controlled to 6.0 to 8.5 to reduce the yield. Without being able to reduce the amount of impurities deposited,
Further, it was found that quinolone carboxylic acids having a large particle size and good filterability can be obtained by simultaneously pouring an aqueous solution of an alkali metal salt of quinolone carboxylic acid and an aqueous solution of an acid together, and completed the present invention.
【０００５】すなわち、本発明は、一般式 化３That is, the present invention has the general formula
【化３】 （式中、Ｒは低級アルキル基、Ｍはアルカリ金属を表
す。）で示されるキノロンカルボン酸類アルカリ金属塩
水溶液に酸水溶液を反応させて一般式 化４[Chemical 3] (In the formula, R represents a lower alkyl group and M represents an alkali metal.) An aqueous solution of an alkali metal salt of a quinolonecarboxylic acid represented by the general formula 4
【化４】 （式中、Ｒは低級アルキル基を表す。）で示されるキノ
ロンカルボン酸類を製造する際に、反応液の最終ｐＨを
６．０〜８．５に制御すること及び／又はキノロンカル
ボン酸類アルカリ金属塩水溶液と酸水溶液とを同時に併
注して反応を行うことを特徴とするキノロンカルボン酸
類の製造方法である。[Chemical 4] (Wherein R represents a lower alkyl group), when producing the quinolonecarboxylic acid, the final pH of the reaction solution is controlled to 6.0 to 8.5 and / or the quinolonecarboxylic acid alkali metal A method for producing a quinolonecarboxylic acid, which is characterized in that a salt aqueous solution and an acid aqueous solution are simultaneously poured together to carry out the reaction.
【０００６】本発明に用いられるキノロンカルボン酸類
アルカリ金属塩は、前記一般式 化３で示される化合物
であるが、式中のＲは低級アルキル基を表し、具体的に
は、メチル基、エチル基、ｎ−プロピル基、イソプロピ
ル基、シクロプロピル基、ｎ−ブチル基、ｎ−ペンチル
基等が挙げられる。また式中のＭはアルカリ金属を表
し、具体的には、ナトリウム、カリウム等が挙げられ
る。また反応原料として用いられるキノロンカルボン酸
類アルカリ金属塩の由来は特に制限されるものではな
く、公知の製造方法によって得られるものはいずれも採
用し得る。The quinolonecarboxylic acid alkali metal salt used in the present invention is a compound represented by the above general formula 3, wherein R represents a lower alkyl group, specifically, a methyl group or an ethyl group. , N-propyl group, isopropyl group, cyclopropyl group, n-butyl group, n-pentyl group and the like. Further, M in the formula represents an alkali metal, and specific examples thereof include sodium and potassium. Further, the origin of the quinolonecarboxylic acid alkali metal salt used as the reaction raw material is not particularly limited, and any one obtained by a known production method can be adopted.
【０００７】キノロンカルボン酸類アルカリ金属塩に反
応させる酸としては、塩酸、硫酸、硝酸等の無機酸、ギ
酸、酢酸等の有機酸いずれも用いることができるが、好
ましくは無機酸を用いるのが良い。As the acid to be reacted with the quinolonecarboxylic acid alkali metal salt, any of inorganic acids such as hydrochloric acid, sulfuric acid and nitric acid, and organic acids such as formic acid and acetic acid can be used, but the inorganic acid is preferably used. .
【０００８】酸を加えた後の反応液の最終ｐＨは６．０
〜８．５に制御するが、ｐＨ８．５より上ではキノロン
カルボン酸類の析出が不十分となり収量が下がる。ま
た、ｐＨ６．０より下では不純物も析出するため、得ら
れたキノロンカルボン酸類の純度が低下する。The final pH of the reaction solution after addition of acid is 6.0.
However, if the pH is higher than 8.5, the precipitation of quinolonecarboxylic acids will be insufficient and the yield will decrease. Further, since impurities are precipitated at a pH below 6.0, the purity of the obtained quinolonecarboxylic acid is lowered.
【０００９】キノロンカルボン酸類アルカリ金属塩水溶
液と酸水溶液とを同時に併注する方法は特に制限される
ものではないが、通常、加温した水にキノロンカルボン
酸類アルカリ金属塩水溶液と酸水溶液とを同時に滴下し
て行う。この際、反応液のｐＨが６．０〜８．５になる
ように滴下量を制御するのが好ましい。The method of simultaneously pouring the aqueous solution of quinolonecarboxylic acid alkali metal salt and the aqueous acid solution is not particularly limited, but usually, the aqueous solution of alkali metal quinolonecarboxylic acid alkali metal salt and the aqueous acid solution are simultaneously added to heated water. Do it by dropping. At this time, it is preferable to control the dropping amount so that the pH of the reaction liquid is 6.0 to 8.5.
【００１０】析出したキノロンカルボン酸類は、加圧濾
過、遠心濾過等の通常の方法で分離し、必要に応じて水
で洗浄した後、乾燥する。The precipitated quinolonecarboxylic acids are separated by a usual method such as pressure filtration and centrifugal filtration, washed with water as necessary, and then dried.
【００１１】[0011]
【発明の効果】本発明方法により、高収率、高純度で濾
過性の良好なキノロンカルボン酸を得ることができる。According to the method of the present invention, it is possible to obtain a quinolonecarboxylic acid having a high yield, a high purity and a good filterability.
【００１２】[0012]
【実施例】以下、本発明を実施例により更に具体的に説
明する。EXAMPLES The present invention will be described in more detail below with reference to examples.
【００１３】実験例１ 内容積５００ｍｌのフラスコに、１−エチル−６，７−
メチレンジオキシ−４−キノロン−３−カルボン酸ナト
リウム塩５８．４ミリモルを含むアルカリ性水溶液２２
２．４ｇを仕込み、１００℃に加熱した。撹拌下、５０
％硫酸１６．８ｇをゆっくり加えｐＨを７．０とし、キ
ノロンカルボン酸を析出させた。固体を濾過後、水洗、
乾燥し、１−エチル−６，７−メチレンジオキシ−４−
キノロン−３−カルボン酸１５．６５ｇを得た。得られ
たキノロンカルボン酸の液体クロマトグラフィーによる
純度は９６．４％であった。また、仕込みナトリウム塩
に対するキノロンカルボン酸の収率は９８．９％であっ
た。Experimental Example 1 1-ethyl-6,7- was added to a flask having an internal volume of 500 ml.
Alkaline aqueous solution containing 58.4 mmol of sodium salt of methylenedioxy-4-quinolone-3-carboxylic acid 22
2.4 g was charged and heated to 100 ° C. Under stirring, 50
Sulfuric acid 16.8 g was slowly added to adjust the pH to 7.0 to precipitate quinolonecarboxylic acid. After filtering the solid, washing with water,
Dried and 1-ethyl-6,7-methylenedioxy-4-
15.65 g of quinolone-3-carboxylic acid was obtained. The purity of the obtained quinolonecarboxylic acid measured by liquid chromatography was 96.4%. The yield of quinolonecarboxylic acid based on the charged sodium salt was 98.9%.
【００１４】実験例２ 硫酸添加後のｐＨを表１に示すように変えた以外は実験
例１と同様の操作を行った。結果を表１に示す。Experimental Example 2 The same operation as in Experimental Example 1 was carried out except that the pH after addition of sulfuric acid was changed as shown in Table 1. The results are shown in Table 1.
【００１５】[0015]
【表１】 [Table 1]
【００１６】実験例３ 内容積５００ｍｌのフラスコに水１３０ｇを入れ９２℃
に加熱した。撹拌下、１−エチル−６，７−メチレンジ
オキシ−４−キノロン−３−カルボン酸ナトリウム塩５
２．５ミリモルを含むアルカリ性水溶液２００ｇと５０
％硫酸１０．１３ｇを反応器内ｐＨが７．５で一定にな
るようにして１時間かけて併注滴下し、キノロンカルボ
ン酸を析出させた。固体を濾過後、水洗、乾燥し、１−
エチル−６，７−メチレンジオキシ−４−キノロン−３
−カルボン酸１３．８０ｇ（純度：９６．０％、収率：
９６．６％）を得た。得られたキノロンカルボン酸の粒
度分布を測定したところメジアン径は３７．７ミクロン
であった。また濾過性指標である濾過比抵抗の値は１．
６３×１０8 ｍ／ｋｇであった。Experimental Example 3 A flask having an internal volume of 500 ml was charged with 130 g of water and at 92 ° C.
Heated to. With stirring, 1-ethyl-6,7-methylenedioxy-4-quinolone-3-carboxylic acid sodium salt 5
200 g of alkaline aqueous solution containing 2.5 mmol and 50
% Sulfuric acid (10.13 g) was added dropwise over a period of 1 hour while the pH in the reactor was kept constant at 7.5 to precipitate quinolonecarboxylic acid. After filtering the solid, washing with water and drying, 1-
Ethyl-6,7-methylenedioxy-4-quinolone-3
-Carboxylic acid 13.80 g (purity: 96.0%, yield:
96.6%). When the particle size distribution of the obtained quinolonecarboxylic acid was measured, the median diameter was 37.7 microns. The value of the filtration resistivity, which is a filterability index, is 1.
It was 63 × 10 8 m / kg.
【００１７】実験例４ 内容積５００ｍｌのフラスコに、１−エチル−６，７−
メチレンジオキシ−４−キノロン−３−カルボン酸ナト
リウム塩５５．８ミリモルを含むアルカリ性水溶液２０
０ｇを入れ、９７℃に加熱した。撹拌下、５０％硫酸を
滴下し、ｐＨを７．７５とし、キノロンカルボン酸を析
出させた。固体を濾過後、水洗、乾燥し、１−エチル−
６，７−メチレンジオキシ−４−キノロン−３−カルボ
ン酸１４．７ｇ（純度：９６．４、収率：９７．２％）
を得た。得られたキノロンカルボン酸の粒度分布を測定
したところメジアン径は９．５ミクロンであった。また
濾過性指標である濾過比抵抗の値は４．２３×１０9 ｍ
／ｋｇであった。Experimental Example 4 1-Ethyl-6,7- was added to a flask having an internal volume of 500 ml.
Alkaline aqueous solution containing 55.8 mmol of sodium salt of methylenedioxy-4-quinolone-3-carboxylic acid 20
0 g was added and heated to 97 ° C. While stirring, 50% sulfuric acid was added dropwise to adjust the pH to 7.75 to precipitate quinolonecarboxylic acid. The solid is filtered, washed with water and dried, and 1-ethyl-
6,7-Methylenedioxy-4-quinolone-3-carboxylic acid 14.7 g (purity: 96.4, yield: 97.2%)
Got When the particle size distribution of the obtained quinolonecarboxylic acid was measured, the median diameter was 9.5 μm. The value of filtration specific resistance, which is an index of filterability, is 4.23 × 10 9 m
It was / kg.
Claims (4)
す。）で示されるキノロンカルボン酸類アルカリ金属塩
水溶液に酸を反応させて一般式 化２ 【化２】 （式中、Ｒは低級アルキル基を表す。）で示されるキノ
ロンカルボン酸類を製造する際に、反応液の最終ｐＨを
６．０〜８．５に制御すること及び／又はキノロンカル
ボン酸類アルカリ金属塩水溶液と酸とを同時に併注して
反応を行うことを特徴とするキノロンカルボン酸類の製
造方法。1. A general formula: (Wherein R represents a lower alkyl group and M represents an alkali metal), and an acid is reacted with an aqueous solution of an alkali metal quinolonecarboxylic acid represented by the general formula: (Wherein R represents a lower alkyl group), when producing the quinolonecarboxylic acid, the final pH of the reaction solution is controlled to 6.0 to 8.5 and / or the quinolonecarboxylic acid alkali metal A method for producing a quinolonecarboxylic acid, which comprises simultaneously pouring an aqueous salt solution and an acid to carry out the reaction.
６，７−メチレンジオキシ−４−キノロン−３−カルボ
ン酸である請求項１記載のキノロンカルボン酸類の製造
方法。2. The quinolonecarboxylic acid is 1-ethyl-
The method for producing quinolonecarboxylic acids according to claim 1, which is 6,7-methylenedioxy-4-quinolone-3-carboxylic acid.
ウム塩である請求項１記載のキノロンカルボン酸類の製
造方法。3. The method for producing a quinolonecarboxylic acid according to claim 1, wherein the alkali metal salt is a sodium salt or a potassium salt.
ンカルボン酸類の製造方法。4. The method for producing a quinolonecarboxylic acid according to claim 1, wherein the acid is an inorganic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29202993A JP3240786B2 (en) | 1993-11-22 | 1993-11-22 | Method for producing quinolone carboxylic acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29202993A JP3240786B2 (en) | 1993-11-22 | 1993-11-22 | Method for producing quinolone carboxylic acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07145170A true JPH07145170A (en) | 1995-06-06 |
| JP3240786B2 JP3240786B2 (en) | 2001-12-25 |
Family
ID=17776611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29202993A Expired - Fee Related JP3240786B2 (en) | 1993-11-22 | 1993-11-22 | Method for producing quinolone carboxylic acids |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3240786B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107586300A (en) * | 2016-07-08 | 2018-01-16 | 上海市计量测试技术研究院 | Novel crystal forms II, its preparation method and its application of oxolinic acid |
-
1993
- 1993-11-22 JP JP29202993A patent/JP3240786B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107586300A (en) * | 2016-07-08 | 2018-01-16 | 上海市计量测试技术研究院 | Novel crystal forms II, its preparation method and its application of oxolinic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3240786B2 (en) | 2001-12-25 |
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