JPH06157538A - Purification of quinolonecarboxylic acid - Google Patents

Abstract

PURPOSE:To provide a process for purifying quinolonecarboxylic acids in high efficiency. CONSTITUTION:Quinolonecarboxylic acids expressed by the formula (R is lower alkyl) is treated with an alkali metal hydroxide, the obtained alkali metal salt of the acid is crystallized by using a hydrated 1-3C alcohol and the crystallized alkali metal salt is treated with an acid.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for purifying quinolonecarboxylic acids useful as medicines or agricultural chemicals.

[0002]

2. Description of the Related Art As a method for purifying quinolonecarboxylic acids, a method of recrystallization from N, N-dimethylformamide is described in JP-B-51-18440.

[0003]

However, the conventional method has a poor refining effect, and a single recrystallization cannot obtain a sufficient refining effect, so that recrystallization is required twice or more. Further, since the solubility of quinolonecarboxylic acids in N, N-dimethylformamide is low, a large amount of solvent is required for recrystallization, and there is a problem that volume efficiency is poor.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems, and as a result, efficiently converted the quinolonecarboxylic acids into alkali metal salts and recrystallized them with hydrous alcohol to efficiently The inventors have found that quinolonecarboxylic acid can be purified and have completed the present invention.

That is, the present invention has the general formula (1):

[Chemical 2] (In the formula, R represents a lower alkyl group.) The quinolonecarboxylic acid is reacted with an alkali metal hydroxide to form an alkali metal salt, and the alkali metal salt has 1 to 3 carbon atoms.
The method for purifying quinolonecarboxylic acids is characterized in that the quinolonecarboxylic acid is crystallized using the above-mentioned hydroalcohol, and then an acid is allowed to act on the alkali metal salt obtained by crystallization.

The quinolonecarboxylic acid used in the present invention is a compound represented by the above general formula (1). In the formula, R represents a lower alkyl group, specifically, a methyl group, an ethyl group, n- Examples thereof include propyl group, isopropyl group, cyclopropyl group, n-butyl group, n-pentyl group and the like. The quinolonecarboxylic acid used as a purification raw material is not particularly limited, and any one obtained by a known production method can be adopted.

The quinolonecarboxylic acid is first reacted with an alkali metal hydroxide to form an alkali metal salt. As the alkali metal hydroxide, sodium hydroxide or potassium hydroxide is used. The amount of the alkali metal hydroxide used may be equimolar or more with respect to the quinolonecarboxylic acid,
It is preferable to use an equimolar to 2-fold molar amount with respect to the quinolonecarboxylic acid.

The obtained alkali metal salt of quinolonecarboxylic acid is crystallized using a hydroalcohol having 1 to 3 carbon atoms. Examples of alcohols used include methanol, ethanol and isopropanol,
It is preferable to use methanol because of its easy recovery. The water / alcohol ratio is usually 1/9 to
A mixed solvent of 9/1 (weight ratio), preferably 1/4 to 2/1 is used. Crystallization is performed by dissolving an alkali metal salt of quinolonecarboxylic acid in hydrous alcohol and cooling it. Since the alkali metal salt obtained by reacting the quinolonecarboxylic acid with an alkali metal hydroxide is obtained as an aqueous solution, crystallization is usually performed by adding alcohols to the aqueous solution of the alkali metal salt without separating the alkali metal salt, If crystals are generated, the temperature is raised to obtain a uniform solution, which is cooled to precipitate crystals. The crystallized crystals are separated by a usual method such as pressure filtration and centrifugal filtration, and washed with hydrous alcohols as necessary.

The obtained alkali metal salt of high-purity quinolonecarboxylic acid is made into an aqueous solution and then an acid is added to precipitate high-purity quinolonecarboxylic acid. As the acid, 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 it is preferable to use inorganic acids. The precipitated high-purity quinolonecarboxylic acid is filtered under pressure,
Separation is carried out by an ordinary method such as centrifugal filtration, washed with water if necessary, and then dried.

[0010]

According to the method of the present invention, quinolonecarboxylic acid can be efficiently purified.

[0011]

EXAMPLES The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples. Example 1 1-Ethyl-6,7-methylenedioxy-4-quinolone-3-carboxylic acid (purity analysis value by liquid chromatography 94.2%) 15 in a flask having an internal volume of 1 liter
0 g, 240 g of water, and 24.2 g of sodium hydroxide were added, and it heated at 60 degreeC and it was set as the uniform solution. Further, 560 g of methanol was added, and the mixture was slowly cooled to 20 ° C. The crystals obtained were filtered. Further, 1670 g of water was added to this crystal to make a uniform solution, and then 40.7 g of 50% sulfuric acid was added,
The pH was adjusted to 8.0 and quinolonecarboxylic acid was precipitated. The solid was filtered, washed with water and dried to obtain 105.9 g of a purified product of 1-ethyl-6,7-ethylenedioxy-4-quinolone-3-carboxylic acid. The purity of the obtained quinolonecarboxylic acid by liquid chromatography was 99.8%.

Example 2 1-Ethyl-6,7-methylenedioxy-4-quinolone-3-carboxylic acid (purity analysis value by liquid chromatography 94.2%) 50 in a flask having an inner volume of 300 ml.
g, 80 g of water, 12.6 g of potassium hydroxide were added, and 60
It heated at 0 degreeC and it was set as the homogeneous solution. 187 g of methanol
Was added, and the mixture was slowly cooled to 20 ° C. The crystals obtained were filtered. Further, 557 g of water was added to the crystals to make a uniform solution, and 10.8 g of 50% sulfuric acid was added to adjust the pH to 8.0 to precipitate quinolonecarboxylic acid. After filtering the solid,
After washing with water and drying, 27.1 g of a purified product of 1-ethyl-6,7-methylenedioxy-4-quinolone-3-carboxylic acid was obtained. The purity of the obtained quinolonecarboxylic acid as determined by liquid chromatography was 99.6%.

Comparative Example 1 1-Ethyl-6,7-methylenedioxy-4-quinolone-3-carboxylic acid (purity analysis by liquid chromatography: 95.7%) was added to a flask having an inner volume of 300 ml.
190 g of N, N-dimethylformamide was added, and
Heat to 50 ° C. to make a homogeneous solution. Cool slowly to 20 ° C. and recrystallize. The precipitated crystals were filtered and dried to obtain 8.8 g of a purified product of quinolonecarboxylic acid. The purity of the obtained quinolonecarboxylic acid by liquid chromatography was 97.8%. Next, to 8.45 g of this quinolonecarboxylic acid, 160 g of N, N-dimethylformamide
Was added, and a second recrystallization was performed by the same operation. As a result, 7.3 g of a purified quinolonecarboxylic acid product was 99.0%.
Obtained with a purity of.

Claims (1)

[Claims] 1. A compound represented by the general formula (1): (In the formula, R represents a lower alkyl group.) The quinolonecarboxylic acid is reacted with an alkali metal hydroxide to form an alkali metal salt, and the alkali metal salt has 1 to 3 carbon atoms.
1. A method for purifying quinolonecarboxylic acids, which comprises crystallization using the hydroalcoholic alcohol, and then allowing an acid to act on the alkali metal salt obtained by crystallization.