JPS6176482A - Method of purifying 2-thiopheneacetic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a drug intermediate, etc. efficiently in high purity, by extracting crude 2-thiopheneacetic acid containing impurities by the use of a fluid in a subcritical or super critical state as an extractant. CONSTITUTION:Crude 2-thiopheneacetic acid containing impurities is purified by extraction. In the operation, the purification is carried out by the use of a fluid in a subcritical or super critical state as an extractant. It is require to keep CO2 in the extraction column at 60-300kg/cm<2> at 25-150 deg.C, preferably at 25-100 deg.C. When CO2 is used as the extractant, it has improved separating ability of 2-thiopheneacetic acid from impurities. It has merits such as treatment at relatively low temperature, simple handling and operation, economic efficiency, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Field of Application) The present invention relates to a method for purifying 2-thiopheneacetic acid. More specifically, the present invention relates to a method of separating highly purified 2-thiophene acetic acid from crude 2-thiophene acetic acid containing impurities using a fluid in a subcritical or supercritical state as an extractant.

2-Thiopheneacetic acid is mainly useful as a pharmaceutical intermediate raw material such as a chemical modifier for synthetic cephalosporin antibiotics.

(Prior art) Generally, the method for producing 2-thiopheneacetic acid is to use thiophene as a starting material, (1) chloromethylate the thiophene, react it with an alkali cyanide to form 2-cyanomethylthiophene, and hydrolyze this. Method (US Pat. No. 2,533,084).

(2) A method in which thiophene is acetylated, further amidated, and then hydrolyzed (West German Patent No. 832755).

(3) Formylation of thiophene and formua! A method using redehyde dimethylcaptal S-oxide via l-methylsulfinyl-1-methylthio-2-chenylethylene (Japanese Unexamined Patent Publication No. 1986-86458),
(4) There are methods such as direct condensation of thiophene with halogenated acetic acid through a photo-φAftλ chemical reaction (Japanese Unexamined Patent Publication No. 1983-R Kutsutomu), but 2-thiopheneacetic acid obtained by these methods generally does not undergo side reactions, etc. The product often has a blue color due to impurities such as tar-like substances generated by the process. Therefore, the purification method uses an adsorbent such as activated carbon alumina or molecular sieves, and a suitable solvent. Methods for recrystallization are known.

(Problems to be Solved by the Invention) In the case of purification methods that involve recrystallization using known adsorbents, activated carbon Since the amount of other refining adsorbents used increases, industrial implementation becomes economically difficult. Furthermore, when activated carbon is used, 50 to 70% of the weight of 2-thiophene acetic acid is adsorbed, so even 2-thiophene acetic acid that does not need to be removed is adsorbed, resulting in highly purified 2-thiophene acetic acid with a low degree of coloration. In order to obtain this, there are problems such as a decrease in yield, which is very disadvantageous for industrial implementation.

In addition, 24-11 minute 1 iti proposed by the applicant
Although the Md method is far superior to the Ike method in terms of purification efficiency and yield, the fact that the concentration of the supernatant layer has to be lowered does not pose any problem in terms of volumetric efficiency (J. do not have.

[Structure of the invention]

(Means for Solving the Problems) In view of the above-mentioned circumstances, the present inventors have conducted intensive studies on a method for industrially advantageously obtaining high-purity 2-thiophene acetic acid from crude 2-thiophene acetic acid. The inventors have discovered that if a fluid in a subcritical or supercritical state is used as an extractant, the drawbacks of the conventional methods can be eliminated and high-quality 2-thiopheneacetic acid can be obtained efficiently, and the present invention has been achieved. Furthermore, the extraction process, type of extractant, extraction and separation conditions, etc., were studied and the present invention was completed.

(Function) A method of separating an organic compound from a mixture containing it using a fluid in a subcritical or supercritical state is described in Japanese Patent Publication No. 5, for example.
Although it is known as described in Japanese Patent No. 4-10589, there is still no knowledge of a method for separating and purifying 2-thiophene acetic acid of higher purity than crude 2-thiophene acetic acid containing impurities.

A fluid in a sub-, critical or supercritical state is a fluid near or above its critical temperature and pressure. For example, ethylene (9.9°Cv 50atm).

It is a fluid that is near or above the critical state, such as carbon dioxide (81° C. e 72.9.atm), and has a density close to that of a liquid and a large diffusion coefficient close to that of a gas. Because of this feature, various compounds can be extracted quickly and efficiently in large quantities, and the extractant can be easily separated. It also has the characteristic that selective extraction can be performed because the ability to dissolve various compounds changes greatly with just a slight change in pressure or temperature.

Generally speaking, in the present invention, fluids in the above-mentioned subcritical or supercritical state (any of these fluids can be used) have an excellent separation ability between impurities and 2.-thiopheneacetic acid, and a relatively low temperature. Carbon dioxide is usually used as the extraction agent because it can enjoy many advantages such as being able to process, being easy to handle and operate, and being economically advantageous.

=5- Hereinafter, embodiments of the present invention will be described based on a flow sheet.

In Figure 1, C02 cylinder 1 and F) pressure 1m1m2
C02 compressed to a predetermined pressure using a heat exchanger 8 is brought to a predetermined extraction temperature to a subcritical or supercritical state and introduced into the extraction column 4. The extraction column 4 is charged with crude 2-thiopheneacetic acid as a raw material in advance. As a result, CO2
The pressure of the C02 phase containing 2-thiopheneacetic acid extracted in the above is reduced through the pressure reducing valve 5.

This is introduced into a separator 6 to separate the liquid or solid extract from the gaseous CO2. The CO2 separated from the extract is cooled in a condenser 7 and recycled through compression m2.

The pressure of C011 in the extraction tower in the above process is 5
0-500 kg/crrP, preferably 60-800
kνQm-temperature, which not only deteriorates the separation accuracy but also requires energy to separate the extractant from the extract. On the other hand, if it is too expensive, the cost of the equipment will increase and there will be problems with economic efficiency.

−〇− Separation of extraction agent and extract can be done not only by the above-mentioned pressure change method, but also by
The temperature change method can also be used for efficient separation, and good results may be obtained when both are used in combination.

(Example) The present invention will be explained in more detail by showing practical examples below.
The present invention is not limited to this.

Example 1 100 g of colored crystals of crude 2-thiophene acetic acid containing 4% by weight of water were packed into an extraction column with an internal capacity of 500 cc.
Extraction was performed using CO2 at 1° C., and the extract was separated at room temperature and atmospheric pressure to obtain 95 g of colorless 2-thiophene acetic acid.

The purity of the obtained colorless 2-thiopheneacetic acid was 99.5%.
The hue of a 2% by weight methanol solution of this was 20% by APHA.

Note that 2M of crude 2-thiophene acetic acid was used as a raw material.

The hue of the % methanol solution was Gardner number 18 or higher.

Example 2 The hue of a 2 wt% methanol solution with a purity of 99.0% is AP
150 g of crystals of 2-thiophene acetic acid No. 60 in HA
was packed into an extraction column with an internal capacity of 550 ee, and extracted using 200 kg/"rn" v of CO2 at a temperature of 41°C in the same process as in Example 1, and the extract was separated at room temperature and atmospheric pressure. The entire amount of colorless 2-thiopheneacetic acid was obtained. The purity of the obtained colorless 2-thiophene acetic acid was 99.7%, and the hue of a Fuyusha% methanol solution of this was 10% by APHA.
It was below the number.

〔Effect of the invention〕

By the method of the present invention, high-grade 2-thiopheneacetic acid can be obtained, and the following superior effects can be achieved compared to conventional methods.

(1) Since the separation effect between 2-thiophene acetic acid and the tar component is large, 2-thiophene acetic acid with a very low degree of coloration can be obtained in high yield.

(2) According to the present invention, steps such as dissolution, crystallization, filtration, and drying, which are necessary in conventional methods, are no longer necessary, and the product can be manufactured by only the extraction step, so the work process is greatly improved.

(3) Compared to the applicant's previous method, the volumetric efficiency is high, so it is highly economical.

[Brief explanation of the drawing]

FIG. 1 is a flow sheet showing an example of an embodiment of the present invention.

Claims (3)

[Claims] (1) A purification method characterized in that a fluid in a subcritical or supercritical state is used as an extractant in purifying crude 2-thiopheneacetic acid containing impurities by extraction. (2) The method according to claim (1), wherein the fluid in a subcritical or supercritical state is carbon dioxide. (3) Fluid in subcritical or supercritical state has a pressure of 60 to 30
The method according to claim (2), wherein the carbon dioxide is 0 kg/cm^2 and a temperature of 25 to 100°C.