JPH05339208A - Production of pyruvic ester - Google Patents

Abstract

PURPOSE:To obtain in high selectivity and yield the subject compound as a raw material for various chemicals or e.g. a solvent for producing semiconductors, by oxidation of a lactic ester. CONSTITUTION:The objective pyruvic ester can be obtained by oxidation of a lactic ester with chlorine or a hypochlorite in the presence of a catalyst, i.e., bromine or a bromine compound (e.g. hydrogen bromide, sodium bromide) under irradiation of rays 300-800 (pref. >=650)nm in wavelength at -5 to 50 deg.C, pref. 0-20 deg.C. The amounts of the catalyst and oxidizing agent to be used are 0.5-30, pref. 2-15mol% and 0.9-1.5, pref. 1 equivalents, respectively, based on the lactic ester.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing pyruvic acid ester. More specifically, it relates to a method for producing pyruvic acid ester, which is used as a raw material for synthesizing various chemicals and as a solvent in semiconductor production, by oxidizing lactate ester.

[0002] Pyruvate is an important intermediate in the metabolic pathway of substances in vivo, and is useful as a raw material when synthesizing various physiologically active substances together with its ester. Further, in recent years, pyruvic acid ester has been used as a solvent for semiconductor production.

[0003]

BACKGROUND OF THE INVENTION Conventionally, pyruvic acid is produced by a method of hydrolyzing acetyl cyanide obtained by the reaction of sodium cyanide and acetyl chloride, or a method of dry-distilling tartaric acid in the presence of potassium hydrogen sulfate. Has been done. However, the method via acetyl cyanide has drawbacks that a large amount of by-products are produced and the yield is low, and the method using tartaric acid as a raw material is expensive and the yield is low.

Therefore, a method of producing pyruvic acid or a pyruvic acid ester by using lactic acid or a lactic acid ester that is inexpensive and industrially advantageous as a raw material and oxidatively dehydrogenating the lactic acid or lactic acid ester has been drawing attention.

As a method for producing pyruvic acid (ester) from lactic acid (ester) as a raw material, for example, (1)
A method for dehydrogenating lactic acid using lactate dehydrogenase or a microorganism having lactate dehydrogenase, (2) a method for oxidizing with an oxidizing agent such as potassium permanganate, (3) a precious metal catalyst such as platinum or palladium (special Japanese Laid-Open Publication No. 54-138514, Japanese Patent Publication
38-3662, JP 61-16263), or metal oxide catalyst (JP 56-19854, JP 54-21982).
Japanese Patent Publication No. 64-11011), and (4) Liquid phase oxidation method using hydrogen peroxide solution (Japanese Patent Laid-Open No. 1-242554).

However, the method using the microorganism of (1) is
There are drawbacks such as difficulty in separating α-ketoglutaric acid produced as a by-product and generation of a large amount of high BOD wastewater.
The method (2) using an oxidizing agent such as potassium permanganate has the drawbacks that the oxidizing agent is expensive and the yield is low at about 50%. In the catalytic oxidation method of (3), the catalyst is expensive, the life of the catalyst is short, the conversion rate is not sufficient, and therefore the separation operation of lactate ester and pyruvate ester having close boiling points is troublesome. It has drawbacks.
The method of using hydrogen peroxide solution of (4) has a problem in terms of cost as an industrial manufacturing method because hydrogen peroxide solution is expensive.

As described above, the conventional method for producing pyruvic acid (ester) using lactic acid (ester) as a raw material is not always satisfactory as an industrial production method. Therefore, an object of the present invention is to provide a method for industrially producing pyruvic acid ester from lactate ester in an industrially advantageous manner.

[0008]

In view of the above, the inventors of the present invention have made extensive studies as to a method of using chlorine or a chlorine-based compound as an oxidant. As a result, bromine or a bromine compound is used as a catalyst and is irradiated with light. It was found that the pyruvic acid ester can be obtained with high selectivity in a high yield when the reaction is carried out in accordance with the present invention, and has arrived at the present invention.

That is, the present invention provides a method for producing a pyruvate ester, which comprises oxidizing a lactate ester with chlorine or hypochlorite in the presence of bromine or a bromine compound while irradiating light. is there. Although a method of oxidizing a secondary alcohol using chlorine or bromine is conventionally known, a method of producing an α-ketocarboxylic acid by oxidizing an α-hydroxycarboxylic acid with chlorine or bromine has not been reported. ..

The method for producing the pyruvic acid ester of the present invention will be described in detail below. Lactate ester In the production method of the present invention, the lactate ester used as a raw material has the following general formula:

Embedded image CH ₃ CH (OH) COOR. Here, R represents an alkyl group having 1 to 6 carbon atoms, specifically, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, and an isomer group thereof. As the lactic acid ester which is a raw material for the method of the present invention, a commercially available one may be used, or one synthesized by a known method may be used.

Catalyst The catalyst used in the method of the present invention may be any catalyst that produces bromine ions in the reaction solution. Specific examples include bromine, hydrogen bromide, sodium bromide, potassium bromide, calcium bromide, magnesium bromide and the like. These catalysts are used in an amount of 0.5 to 30 mol%, preferably 2 to 15 mol% based on the lactate ester. If it is less than 0.5 mol%, oxidation by chlorine does not occur sufficiently, and if it exceeds 30 mol%,
For example, there is a possibility that by-products such as a bromide of pyruvate ester will increase.

Oxidizing Agent In the method of the present invention, chlorine or hypochlorite is used as an oxidizing agent. As the hypochlorite, sodium hypochlorite, potassium hypochlorite or the like can be used.
The amount of oxidant used is 0.9 to 1.5 equivalents to lactate,
Preferably 1 equivalent is used. When bromine is used as the catalyst, bromine also acts as an oxidizing agent, so the total amount of chlorine and bromine may be within the above range.

Solvent In the method of the present invention, an organic solvent inert to these reagents is used as a solvent for the raw material lactic acid and the produced pyruvic acid. As such an organic solvent, halogenated hydrocarbons such as methylene chloride, chloroform, and 1,1,1-trichloroethane are preferably used. Also, water that dissolves chlorine as an oxidant or hypochlorite is used together with an organic solvent, so that water-organic solvent is not uniform.
The reaction is carried out in a phase system with sufficient stirring.

Reaction conditions The lactate ester and the catalyst are dissolved in a two-phase mixed solvent of water and a water-insoluble solvent. Here, the concentration of the raw material lactate ester in the water-insoluble solvent is set to about 1 to 30% by weight, and the reaction solution temperature is adjusted to -5 to 50 ° C, preferably 0 to 20 ° C while irradiating light, and an oxidizer is added ( Introduce. Since heat is generated by the reaction, it is necessary to add the oxidizing agent gradually and to cool the reaction medium appropriately in order to keep the temperature in the above range.

In the method of the present invention, the light irradiated during the reaction is
Light having a wavelength of 300 to 800 nm, such as visible light, near infrared light, and near ultraviolet light, and light having a wavelength of 650 nm or more is preferable. When chlorine gas is used as the oxidant, chlorine gas is bubbled under the reaction solution. After completion of the reaction, excess chlorine remaining in the solvent is removed by introducing an inert gas such as nitrogen. When hypochlorite is used as the oxidant, a strong acid such as concentrated hydrochloric acid is used to carry out the reaction while maintaining the reaction solution in an acidic region, preferably pH 4 or less.

The progress of the reaction may be traced by chromatography or the like and terminated when the disappearance of the lactate ester is confirmed. Generally, the reaction time is 1 to 10 hours. After the reaction, the target pyruvate ester can be obtained in high purity by treating with an aqueous solution of sodium hydrogen carbonate and sodium sulfite, separating the organic layer, and purifying and isolating by distillation under reduced pressure.

[0017]

EXAMPLES The present invention will be described below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

Example 1 A stirrer, a chlorine introduction tube, a thermometer and a cooler were installed in a draft irradiated with two lights of a 20 W fluorescent lamp.
Set up a 00 ml three neck flask. Dichloromethane 2
70 g, ethyl lactate 41.6 g (353 mmol), bromine
Add 2.8 g (17.5 mmol) and 45 g of water and stir.
After cooling from the outside and adjusting the temperature in the flask to 5 ° C, chlorine is blown into the flask from the inlet tube under stirring to generate heat after a few minutes and the internal temperature rises. After adding 25.7 g of chlorine over a period of time, blow excess nitrogen by blowing nitrogen gas.

When the organic layer was analyzed by gas chromatography, the yield of ethyl pyruvate was 85% and the residual ethyl lactate was 0.2%. The organic layer is separated, a solution obtained by dissolving 5 g of sodium hydrogen carbonate and 3 g of sodium sulfite in 100 g of water is added, and the mixture is stirred for 30 minutes. After standing still and washing with 50 g of water, the solvent was distilled off, and the residue was distilled under reduced pressure.
32.2 g (278 mmol, yield 78.8%) of ethyl pyruvate was obtained.

Example 2 A 1-liter four-necked flask was charged with a dropping funnel, thermometer, and pH.
Equipped with meter, cooler and stirrer, ethyl lactate 50g
(424 mmol), dichloromethane 338 g, and a solution prepared by dissolving 1.7 g (17 mmol) of sodium bromide in 30 g of water are added, and the mixture is cooled to 7 ° C. While maintaining this temperature, 9.5 g of 35% hydrochloric acid is added with stirring. Diameter 20
254.6 g of a 12.4% sodium hypochlorite aqueous solution was added dropwise over 3 hours while spot-irradiating the reaction liquid surface with a halogen light irradiation device of mm. After completion of dropping, the mixture was aged for 30 minutes and then the same operation as in Example 1 was carried out to obtain 39.8 g (343 mmol, 81.0%) of ethyl pyruvate.

Example 3 In place of sodium bromide, 1.35 g (8.5 mmol) of bromine was added and the reaction was carried out in the same manner as in Example 2. The same operation was carried out to obtain 40.4 g of ethyl pyruvate (348 mmol, yield). 82.2%).

Example 4 By repeating the same procedure as in Example 2 except that 44 g (424 mmol) of methyl lactate was used instead of ethyl lactate, 30.3 g (297 mmol, methyl pyruvate) of methyl pyruvate was obtained.
Yield 70.0%) was obtained.

Example 5 1182 g (10 mol) of ethyl lactate, 6 liters of dichloromethane and 32 g (0.2 mol) of bromine were charged into a 20 liter glass reactor and cooled to 7 ° C. 500g of water
And 225 g of 35% hydrochloric acid are added, and while irradiating the reactor with an incandescent lamp of 300 W, 13.2% sodium hypochlorite is added.
5531 g (29.8 mol) are added at 10-15 ° C. After the reaction, the same operation as in Example 1 was performed to obtain 947 g (8.2 mol, yield 82.0%) of ethyl pyruvate.

[0024]

INDUSTRIAL APPLICABILITY According to the method of the present invention in which lactic acid ester is oxidized by chlorine or hypochlorite while irradiating with light in the presence of bromine or a bromine compound, the method of synthesizing various physiologically active substances and semiconductor production can be achieved. A pyruvic acid ester useful as a solvent or the like can be produced with high purity and high yield.

Claims (1)

[Claims] 1. A method for producing a pyruvate ester, which comprises oxidizing a lactate ester with chlorine or hypochlorite while irradiating light in the presence of bromine or a bromine compound.