JPH0261472B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing thiophenecarboxylic acids, and more particularly to a method for producing thiophenecarboxylic acids using thiophene aldehydes as raw materials. Thiophenecarboxylic acids, which are useful as intermediate raw materials for cephalosporin antibiotics, are produced industrially mainly by using thiophene as a starting material to produce acetylthiophene and oxidizing it. In the process, there are many problems in the treatment of waste and by-products, and since a large amount of oxidizing agent is used, there are many economic disadvantages. As a method for producing thiophenaldehydes by oxidizing them, for example, (a) Fehling's reagent (JAC
S., 75 , 989 (1953)), (b) by silver oxide (Org.Syn.
Coll.Vol., 919), (c) Oxygen in hexamethylphosphoric triamide (JOC 30 , 3520
(1965)) have been reported. However, none of these production methods can be said to be industrially applicable. The present invention provides an industrially advantageous method for producing thiophenecarboxylic acids by oxidizing thiophene aldehydes with hypohalites. That is, the present invention provides a general formula in which a thiophene aldehyde represented by the general formula () K0638 (in the formula, R represents hydrogen, halogen, or a lower alkyl group) is reacted with a hypohalite in an alkaline aqueous medium. () K0639 (in the formula, R is the same as above). In the method of the present invention, () dispersed in water is oxidized with hypohalite, but when the reaction system becomes acidic due to the formation of (), decomposition of the hypohalite occurs. Therefore, it is necessary to keep the reaction system alkaline at all times. Water-soluble alkaline substances to be used as an alkaline water medium include hydroxides of alkali metals or alkaline earth metals such as sodium hydroxide and calcium hydroxide, and alkali metal carbonates such as sodium carbonate. For practical purposes, sodium hydroxide is preferably used. Further, the amount of alkaline substance required must be sufficient to neutralize the () produced. Therefore, for example, when using sodium hydroxide as an alkaline substance, it is used in at least an equimolar amount with (). In addition, the alkaline substance may be added in its entirety from the start of the reaction, or it may be added in appropriate portions during the course of the reaction so that the aqueous medium in the reaction system is always alkaline; It is easy to operate. Examples of hypohalites include alkali metal salts and alkaline earth metal salts of hypochlorous acid or hypobromous acid, and sodium hypochlorite and calcium hypochlorite are practical. Furthermore, since the hypohalite does not need to be in solid form and is used as an aqueous solution, it is preferable to use an aqueous sodium hypochlorite solution, which is easily available industrially as an aqueous solution containing about 6 to 12% available chlorine. used. The required amount of hypohalite is at least equimolar, preferably 110 to 200 mol %, based on the effective halogen content (). If you heat an aqueous solution containing () and an alkaline substance while stirring and then add a hypohalite aqueous solution, the resulting () may turn yellow, so proceed as follows. It is better. That is, a reaction system in which () was mixed with an aqueous solution of an alkaline substance and a hypohalite was gradually heated to about 50°C while stirring, continued stirring at that temperature for 4 to 5 hours, and then heated to about 50°C. Continue stirring until the temperature rises to 70°C and the effective halogen content disappears. This reaction produces () as an alkali salt, so after the reaction is complete, unreacted () is extracted and removed from the reaction product solution using an organic solvent that does not mix with water, such as toluene or methylene chloride, and the aqueous layer is extracted with mineral acid. For example, by adjusting the pH to 1 to 2 with hydrochloric acid, sulfuric acid, etc. to precipitate (), filtering, washing with water, and drying, colorless crystals () can be obtained in a yield of about 80%. In the present invention, if the reaction system is heated rapidly, the reaction may be intense and the decomposition of the hypohalite may take priority. Therefore, by adding the remaining hypohalite to the product solution in which the reaction has partially proceeded using a portion of the required amount of hypohalite, it is possible to prevent the reaction from proceeding violently. That is, 5 to 50 mol% as effective halogen for () and () in an alkaline aqueous medium.
The product solution obtained by reacting an amount of hypohalite at 50 to 100°C is reacted with hypohalite at 50 to 100°C. Further, the alkaline substance may be added in its entirety from the start of the reaction, or may be added in portions during the progress of the reaction. The amount of hypohalite added at the start of the reaction must be such that the reaction does not occur violently even if the reaction system is heated rapidly.
Hypohalite is added in an amount of 7 to 30 mol%, preferably 7 to 30 mol%. More specifically, a reaction system in which (), an alkaline substance, and an aqueous solution of hypohalite in the above amount are mixed is heated to 50 to 100°C, preferably about 70°C, while stirring, The remainder of the hypohalite is added over 2 to 3 hours at the same temperature, and stirring is continued for an additional 1 to 2 hours at the same temperature. In the reaction system of the present invention, water-soluble (2) is dispersed in an emulsion at the initial stage of the reaction, but as the reaction progresses, unreacted (2) tends to aggregate in the form of oil droplets. For this reason, it is advantageous in carrying out the present invention to add a cosolvent or surfactant such as tetrahydrofuran to the reaction system to aid in dispersion of () in the alkaline aqueous medium during the course of the reaction. The present invention will be further explained below with reference to Examples.
The 2-thiophene aldehyde used in the examples is made from thiophene and can be easily obtained by the Wills-Meyer reaction. Example 1 4.0 g (0.1 mol) of hydrogen hydroxide atoms (purity 97%) was dissolved in 20 ml of water, and 2-thiophenaldehyde
Mix 11.2g (0.1mol) and 108g (0.14mol) of an aqueous sodium hypochlorite solution with 10% available chlorine at room temperature.
The temperature was raised to 50°C while stirring, and stirring was continued at this temperature for 4 hours. Next, the temperature was raised to 70°C and stirring was continued for 2 hours. At this point, most of the available chlorine in the reaction solution disappeared. The reaction product solution was cooled, unreacted 2-thiophenaldehyde was removed using 20 ml of methylene chloride, and 17 ml of concentrated hydrochloric acid was added to the aqueous layer.
The pH was adjusted to 1, the precipitated crystals were collected, washed with water, and dried to produce colorless 2-thiophenecarboxylic acid (melting point 126~
126.5°C) 9.9g was obtained. Yield 77.4% Example 2 Sodium hydroxide (purity 97%) 4.0g (0.1 mol)
Dissolve 2-thiophenaldehyde in 20ml of water.
11.2 g (0.1 mol) and 11 g of 108 g (0.14 mol) of an aqueous sodium hypochlorite solution containing 10% available chlorine were added, and the temperature was raised to 70°C while stirring. While continuing to stir at this temperature, the remaining amount of the sodium hypochlorite aqueous solution was added dropwise over 2 hours, and then at the same temperature.
Stirring was continued for 1.5 hours. At this point, most of the available chlorine content after the reaction had disappeared. The reaction product solution was treated in the same manner as in Example 1 to obtain 10.5 g of colorless 2-thiophenecarboxylic acid. Yield: 82.0%. Examples 3 to 6 The thiophenecarboxylic acids shown in Table 1 were produced in substantially the same manner as in Example 2.

[Table] Example 7 The reaction was carried out in the same manner as in Example 2, except that 5 ml of funnel oil was added to the reaction solution before starting the dropwise addition of the sodium hypochlorite aqueous solution at 70°C in Example 2, and the reaction was completed. Thereafter, without removing unreacted 2-thiophene aldehyde with methylene chloride, acid precipitation was performed with hydrochloric acid, and the precipitate was washed with water and dried to obtain 11.1 g of 2-thiophenecarboxylic acid. Yield 87.0%.

Claims (1)

[Claims] 1. Reacting a thiophene aldehyde represented by the general formula K0636 (wherein R represents hydrogen, halogen, or a lower alkyl group) with a hypohalite in an alkaline aqueous medium. A method for producing a thiophene carboxylate represented by the general formula K0637 (wherein R is the same as above), characterized by: 2. Add 50 to 50% of hypohalite to the product solution obtained by reacting thiophene aldehydes and hypohalite in an amount of 5 to 50 mol% as an effective halogen to the aldehydes at 50 to 100°C. The manufacturing method according to claim 1, wherein the reaction is carried out at 100°C.