JPS5813530B2 - Alpha − Ketosanno Seizouhou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing α-keto acids, and more particularly to aliphatic carboxylic acids, phenylacetic acid, p-hydroxyphenylacetic acid, or indoleacetic acid, derivatives thereof, or mixtures thereof. The present invention relates to a method for producing an α-keto acid, which comprises reacting with carbon dioxide gas in the presence of an iron-sulfur complex in a reduced state to fix carbonic acid.

Up to now, methods for producing α-keto acids include (1) α-
Method for oxidizing oxyacids (2) Method for hydrolyzing α-keto acid nitrile obtained by treating acid chloride with copper cyanide (3) Method for hydrolyzing oxime obtained from acetoacetate or malonic acid However, all of these production methods require multiple steps and produce many by-products, so it is difficult to say that they are effective synthetic methods.

In contrast, the purpose of the present invention is to synthesize ketocarboxylic acids in one step by using generally well-known and easily available carboxylic acids as raw materials and reacting them with carbon dioxide, which has little utility as a chemical raw material. There is a particular thing.

Furthermore, there are many types of ketocarboxylic acids that can be obtained by the method of the present invention.

This can be said to be a major advantage of the present invention compared to the above-mentioned known method for synthesizing ketocarboxylic acids.

The carboxylic acids used in the present invention include formic acid, acetic acid,
These include aliphatic carboxylic acids such as lactic acid, isolactic acid, isovaleric acid, methylbutyric acid, aminovaleric acid, glycolic acid, and succinic acid, phenylacetic acid, p-hydroxyphenylacetic acid, and indoleacetic acid. Examples include acid anhydrides, acid esters, and thiol esters.

Examples of the alcohol and thioalcohol components that produce acid esters and thiol esters used in the present invention include aliphatic or aromatic alcohols having 1 to 20 carbon atoms, thioalcohols, and mixtures thereof.

Particularly preferred in the present invention is the use of thiol esters.

One of the features of the present invention is that an iron-sulfur complex in a reduced state is used as a catalyst when synthesizing an α-keto acid by reacting a carboxylic acid with carbon dioxide gas.

Examples of iron-sulfur complexes that can be used in the present invention include compounds having the following structural formula.

(R represents a methyl group, an ethyl group, a butyl group, or a phenyl group, and ph represents a phenyl group.

) among others Compounds having the structural formula are preferred.

Further, the present invention is characterized in that the iron-sulfur complex used as a catalyst is reduced with an inorganic or organic reducing agent and used in a reduced state.

All inorganic and organic reducing agents are effective as the reducing agent used for reducing the synthetic iron-sulfur complex, and there are no particular limitations.

The iron-sulfur complex used in the present invention is insoluble in commonly used solvents such as water, alcohol, ether, and benzene, but becomes soluble in the above-mentioned solvents when reduced.

In the reaction, the above single solvent or mixed solvent can be used as a reaction solvent, but methanol, tetrahydrofuran, etc.
A methanol/water solvent is preferred.

The synthesis of α-keto acids according to the method of the present invention is carried out by reducing the iron-sulfur complex with a reducing agent and reacting the carboxylic acid or its derivative with carbon dioxide gas.

This α-keto acid synthesis reaction is characterized in that it can be carried out at room temperature and normal pressure, but it can also be carried out under pressure.

The method of the present invention uses carbon dioxide gas, which is cheap and easy to supply, as a raw material, and the iron-sulfur complex that is the catalyst can be reused, which reduces product costs and has industrial value in terms of recycling resources. can be said to be extremely large.

Examples of the present invention will be given below to explain the present invention more clearly.

However, this is merely an example, and the invention is not limited thereto.

Example 1 110 mg of iron-sulfur complex and 2.5 g of sodium hydrosulfite were placed in a reactor equipped with an efficient cooling tube.
, 0.5 g of sodium bicarbonate, 1.09 m of n-octylthiol acetate and 120 m of phenylhydrazine.
The reaction was carried out by blowing carbon dioxide gas at room temperature for 8 hours with efficient stirring using 20 ml of tetrahydrofuran, 5 ml of methanol, and 5 ml of water as solvents.

After the reaction is completed, the reaction mixture is filtered, and the filtrate is removed by ether extraction under alkaline conditions (about pH 10) to remove unreacted esters, etc., and the phenylhydrazone of pyruvic acid in the aqueous layer is transferred to the ether layer at about pH 4. The mixture was extracted with ether and the ether was removed to obtain phenylhydrazone of pyruvic acid.

The phenylhydrazone of pyruvic acid obtained by the above method was identified by comparing the Rf value of the sample and the Rf value of the standard product using thin layer chromatography.

That is, phenylhydrazone of pyruvic acid obtained by reacting commercially available pyruvic acid and phenylhydrazine was used as a standard product, silica gel was used as a stationary phase, and n-butanol-acetone-water (10:10:5) was used. When analyzed by thin layer chromatography using phenylhydrazone of pyruvic acid obtained in Example 1 as a developing solvent, the Rf value of the phenylhydrazone of pyruvic acid obtained in Example 1 was 0.2, which was exactly the same as the Rf value of the standard product.

In addition, phenylhydrazone of biruvic acid methyl ester obtained by further treating the above standard product with diazomethane was used as a standard product, silica gel was used as a stationary phase, and chloroform-methanol-acetic acid-water (30:15:4:1) was added. When analyzed by thin layer chromatography using a developing solvent, the Rf value of the ester form of the ferhydrazone of pyruvic acid obtained in Example 1 treated with diazomethane was 0.7, which was exactly the same as the Rf value of the standard product. Indicated.

Example 2 26 mg of ferrous chloride in a reactor equipped with an efficient condenser
, sodium sulfide 13 mg, mercaptoethanol 3.
A synthetic iron-sulfur complex was prepared using 5g of aminoethylthiol phenyl acetate, 500mg of sodium bicarbonate, and phenylhydrazone 12 under degassing.
0mg and 20ml of tetrahydrofuran as a solvent.
Using 10 ml of methanol and 5 ml of water, carbonic acid was blown into the mixture at room temperature for 10 hours while stirring efficiently to carry out the reaction.

After the reaction was completed, purification was performed in the same manner as in Example 1 to obtain phenylhydrazone of phenylpyruvic acid.

The phenylpyruvic acid obtained by reacting the phenylhydrazone of phenylpyruvic acid obtained and the ester form obtained by further treating this with diazomethane with commercially available phenylpyruvic acid and phenylhydrazine as a standard product. Analysis was performed in the same manner as in Example 1, except that the phenylhydrazone of phenylhydrazone or the phenylhydrazone of phenylpyruvate methyl ester obtained by treating this with diazomethane was used, and the Rf values were 0.4 and 0.0, respectively.
8, showing exactly the same Rf value as the corresponding standard product.

Example 3 100 mg of synthetic iron-sulfur complex and 5.0 g of sodium hydrosulfite were placed in a reactor equipped with an efficient cooling tube.
, 500 mg of sodium hydrogen carbonate, and 500 mg of n-octylthiol acetate were added, and while stirring efficiently, using 20 ml of tetrahydrofuran, 10 ml of methanol, and 5 ml of water as solvents, a reaction was carried out by blowing carbon dioxide gas at room temperature for 7 hours.

After the reaction is completed, the reaction mixture is filtered, and the filtrate is extracted with ether under alkaline conditions (about pH 10) to remove unreacted esters, etc., and then the pyruvic acid in the aqueous layer is transferred to the ether layer at about pH 4 and extracted with ether. , after concentrating the ether under reduced pressure,
Almost pure pyruvic acid was obtained using column chromatography.

The pyruvic acid obtained by the above method was analyzed by thin layer chromatography using commercially available pyruvic acid as a standard, silica gel as a stationary phase, and pyridine-petroleum ether (1:2) as a developing solvent. The Rf value was 0.4, which was exactly the same as the Rf value of the standard product.

In addition, analysis was conducted by thin layer chromatography using pyruvic acid methyl ester obtained by treating commercially available pyruvic acid with diazomethane as a standard product, silica gel as a stationary phase, and chloroform as a developing solvent. The Rf value of the ester obtained by treating pyruvic acid with diazomethane was 0.7, which was exactly the same as the Rf value of the standard product.

Example 4 Phenylhydrazone of p-hydroxyphenylpyruvic acid was obtained in the same manner as in Example 1 except that n-octylthiol p-hydroxyphenyl acetate was used instead of n-octylthiol acetate.

Regarding the obtained phenylhydrazone of p-hydroxyphenylpyruvic acid and the ester obtained by further treating this with diazomethane, commercially available p-
Phenylhydrazone of p-hydroxyphenylpyruvic acid obtained by reacting hydroxyphenylpyruvic acid with phenylhydrazine, or a phenylhydrazone of p-hydroxyphenylpyruvic acid methyl ester obtained by treating this with diazomethane. When analyzed in the same manner as in Example 1 except for using enylhydrazotz, the Rf values were 0.
1 and 0.6, showing exactly the same Rf value as the corresponding standard product.

Example 5 Example 1 except that n-octylthiol indole acetate was used instead of n-octylthiol acetate.
Phenylhydrazine of β-indole-3-pyruvic acid was obtained in the same manner as above.

Regarding the obtained phenylhydrazone of β-indole-3-pyruvic acid and the ester obtained by treating this with diazomethane, commercially available β-indole-3-pyruvic acid and phenylhydrazine were used as standard products. Example 1 except that phenylhydrazone of β-indole-3-pyruvic acid obtained by the reaction or phenylhydrazone of β-indole-3-pyruvic acid notyl ester obtained by treating this with diazomethane was used. When analyzed using the same method as above, the Rf values were 0.2 and 0.6, respectively, which were exactly the same as the Rf values of the corresponding standard products.

Claims (1)

[Claims] 1. Reacting an aliphatic carboxylic acid, phenylacetic acid, p-hydroxyphenylacetic acid, or indoleacetic acid, or a derivative thereof, or a mixture thereof with carbon dioxide gas in the presence of an iron-sulfur complex in a reduced state to fix carbonic acid. A method for producing an α-keto acid, characterized by: