JPH0617275A - Production of alpha-ketonate - Google Patents

Abstract

PURPOSE:To provide the process for production of the alpha-ketonate which is electrochemically advantageous. CONSTITUTION:The alpha-hydroxilic acid ester is dispersed in a liquid mixture composed of an aq. soln. of at least one halides selected from the group consisting of alkal metal halides, onium halide salts and alkaline earth metal halides and a poly-lower hydrocarbon halide and the liquid mixture is energized. More preferably, a ruthenium compd. is incorporated into the liquid mixture and a pH buffer is incorporated into the aq. soln. of the halides.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION α-Keto acids and α-keto acid esters are used as synthetic intermediates in various organic synthetic reactions.
It is also an important chemical in the field of fine chemicals such as fragrances, food additives, electronic materials and pharmaceutical raw materials. The present invention relates to a method for producing such an α-keto acid ester.

[0002]

As a method for producing an α-keto acid ester,
Conventionally, (1) Method for liquid-phase oxidation of α-hydroxy acid ester with potassium permanganate Organic Syntheses, Coll.
Vol. IV. Item 467 (1963)), (2) Method of liquid-phase oxidation of α-hydroxy acid ester in the presence of tungsten trioxide (JP-A-58-62136), (3) α-
A method of subjecting a hydroxy acid ester to liquid phase oxidation in the presence of at least one of titanium dioxide, zirconium dioxide and niobium pentoxide (JP-A-63-132859),
(4) Method of liquid-phase oxygen oxidation of α-hydroxy acid ester in the presence of a noble metal catalyst such as platinum or palladium (Japanese Patent Laid-Open No. 138514/1979), (5) Semi-melted alumina with iron oxide. A method of vapor-phase oxidation of an α-hydroxy acid ester in the presence of a catalyst containing molybdenum oxide (Japanese Patent Publication No. 38-3662), (6) a mixture of ammonium metavanadate, oxalic acid and water is added.
A method of vapor-phase oxidizing an α-hydroxy acid ester using a catalyst obtained by adhering it to a carrier having a Ka value in the range of 3.8 to 9.8 and then calcining it (JP-B-57-24336). ,
(7) A method of oxidizing an α-hydroxy acid ester at 450 ° C. using a silver catalyst treated with a phosphate (JP-A-61-61)
-97247), (8) A method of oxidizing with a bromate using a ruthenium-based catalyst (JP-A-1-30505).
No. 3) is known.

However, the above method (1) requires expensive potassium permanganate and is industrially difficult to treat after the reaction. Above (2), (3) and (4)
In addition to the low yield of α-keto acid ester,
Since the boiling points of the keto acid ester and the α-hydroxy acid ester are close to each other, it is very difficult to separate them by distillation after the reaction. Furthermore, (5),
In the methods (6) and (7), the preparation of the catalyst is complicated, the life of the catalyst is short, and the equipment, including its regeneration, is large in scale. The method (8) uses an expensive catalyst and an oxidizing agent and is not preferable as a method for industrially inexpensively producing an α-keto acid ester.

[0004]

DISCLOSURE OF THE INVENTION The inventors of the present invention have earnestly studied in order to solve the problems in the conventional production of α-keto acid ester as described above, and as a result, α-hydroxy acid ester was electrochemically analyzed. The present invention has been completed by finding a method for industrially and easily producing an α-keto acid ester by oxidation.

[0005]

The method for producing an α-keto acid ester according to the present invention comprises at least one halide selected from the group consisting of alkali metal halides, onium halide salts and alkaline earth metal halides. It is characterized in that the α-hydroxy acid ester is dispersed in a mixed liquid of an aqueous solution and a polyhalogenated lower hydrocarbon, and electricity is applied.

In the method of the present invention, as the α-hydroxy acid ester, for example, methyl lactate, ethyl lactate, propyl lactate and the like are used. The method of the present invention comprises D-α-
It can be applied to any of hydroxy acid ester, L-α-hydroxy acid ester and DL-α-hydroxy acid ester, and the gas chromatographic analysis shows that the yield of the target substance does not differ much depending on the distinction between these isomers. Have been confirmed by.

In the present invention, as the alkali metal halide, chlorides such as lithium, sodium and potassium, bromides or iodides are preferably used. Normal,
Lithium chloride, lithium bromide, lithium iodide, sodium chloride, sodium bromide, sodium iodide, potassium chloride, potassium bromide, potassium iodide and the like are used, but particularly industrially, sodium bromide or bromide is used. Potassium is preferably used.

The halogenated onium salt is a compound represented by the general formula R ₁ R ₂ R ₃ R ₄ EX, in which R ₁ , R ₂ , R ₃ and
R ₄ represents hydrogen, an alkyl group, an aryl group, an aralkyl group or an allyl group, and may be the same as or different from each other. Typically, methyl, ethyl, propyl, butyl,
Hexyl, heptyl, dodecyl, cetyl, phenyl, benzyl and the like can be exemplified. E represents a nitrogen atom or a phosphorus atom, and X represents a chlorine, bromine or iodine atom.

Therefore, specific examples of such an onium halide salt include, for example, ammonium chloride, ammonium bromide, ammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide, tetramethylammonium iodide, tetraethylammonium chloride, Tetraethylammonium bromide, tetraethylammonium iodide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrapropylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium iodide, cetyltrimethylammonium chloride, odor Cetyltriphenylphosphonium bromide, benzyltriethylammonium chloride, cetyltriethylammonium bromide, heptyltriphenylammonium bromide And the like can be given Honiumu. However, these onium salts are merely examples,
In the present invention, all onium salts generally known as phase transfer catalysts can be used.

As the halogen alkaline earth metal, chlorides, bromides or iodides of magnesium and calcium are used. Particularly, calcium chloride or magnesium chloride is industrially advantageously used. The above-mentioned alkali metal halide, onium salt and alkaline earth metal halide are used alone or as a mixture of two or more kinds.

The above-mentioned aqueous solution of halide means a transparent aqueous solution or a suspended aqueous solution containing these halides. The concentration of the halide in such an aqueous solution is not particularly limited, but is usually in the range of 0.05 to 10 mol / l. Next, in the present invention, the polyhalogenated lower hydrocarbon is a lower aliphatic hydrocarbon which is liquid at room temperature, particularly a polyhalide having 1 or 2 carbon atoms, such as methylene chloride, chloroform and tetrachloride. Examples thereof include carbon and trichlorethylene. Generally, it has 1 carbon atoms, which is known as a solvent.
Alternatively, the polyhalogenated lower aliphatic hydrocarbon of 2 is preferable.

In the present invention, the α-hydroxy acid ester is dispersed in a mixed solution of the above-mentioned aqueous solution of a halide and a polyhalogenated lower hydrocarbon, and the mixture is energized to obtain the α-keto acid ester. To get Here, the mixed liquid is obtained by mixing and stirring the aqueous solution of the halide and the polyhalogenated lower hydrocarbon.
Such a mixed liquid may be, for example, an emulsion.

According to the present invention, α-
The hydroxy acid ester is dispersed. That is, according to the present invention, dispersing an α-hydroxy acid ester in such a mixed solution means that the mixed solution of the aqueous solution of the above-mentioned halide and the polyhalogenated lower hydrocarbon is dependent on the respective affinity. , Dissolved, or distributed as fine spheres.

Furthermore, according to the present invention, the mixed solution preferably contains a ruthenium compound, and the aqueous solution of the halide may contain a pH buffering agent. According to the present invention, the α-hydroxy acid ester is thus dispersed in a mixed solution of an aqueous solution of a halide and a polyhalogenated lower hydrocarbon, and a ruthenium compound is further contained in the aqueous solution of a halide, and / or Alternatively, a pH buffer is contained, and a direct current or an alternating current is passed through the mixed solution through an anode and a cathode to oxidize the α-hydroxy acid ester to obtain an α-keto acid ester.

According to the method of the present invention, ruthenium dioxide dispersed in an aqueous solution of a halide is electrically oxidized to ruthenium tetraoxide, which is dissolved in a polyhalogenated lower hydrocarbon. This ruthenium tetroxide is α-
At the same time as oxidizing the hydroxy acid ester, it is reduced to ruthenium dioxide and dispersed in an aqueous solution of a halide, and then ruthenium dioxide dispersed in an aqueous solution of a halide is again electrically oxidized, Regenerate ruthenium tetroxide. Thus, the ruthenium compound promotes the oxidation of the α-hydroxy acid ester to the α-keto acid ester while being repeatedly redox itself.

In the present invention, the ruthenium compound can assist the oxidation of the α-hydroxy acid ester and reduce the required amount of electricity. Such ruthenium compounds include ruthenium metals or compounds whose valence of ruthenium is from zero valence to various oxidation states, and specific examples include, for example, metal ruthenium powder, colloidal ruthenium, ruthenium dichloride, and diodor. Ruthenium oxide,
Examples thereof include ruthenium oxide, ruthenium acetylacetonate, ruthenium trichloride, ruthenium tribromide and ruthenium triiodide.

The amount of the ruthenium compound used is 10 mol or less, preferably 0.5 mol or less, relative to 1 mol of the α-hydroxy acid ester. However, even if it is used in excess of 10 mols per mol of α-hydroxy acid ester, the effect corresponding to it cannot be obtained, which is rather economically disadvantageous. The pH buffer used in the present invention is an ordinary salt-type buffer and is not particularly limited, and examples thereof include sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium citrate, and potassium citrate. Examples thereof include sodium borate. According to the present invention, such a pH buffer is preferably dissolved in an aqueous solution of a halide, and electric current is applied. The concentration of the pH buffer is not particularly limited, but is usually 10 mol / l or less.

According to the method of the present invention, hydrolysis of α-hydroxy acid ester and α-keto acid ester is carried out by dissolving a pH buffer in an aqueous solution of a halide and applying an electric current. Can be suppressed and the yield of α-keto acid ester can be increased.

[0019]

The present invention will be described below with reference to examples.
The present invention is not limited to these examples. In the following examples, the following reactor was used. Anode platinum plate (thickness 50 μm, length 7 cm, width 4 cm) in a 500 ml beaker with rubber lid and cathode copper plate (thickness 100 μm, length 7 cm, width 4 cm) facing it.
cm) and 2 cm in parallel with each other, and the cathode was placed in a unglazed ceramic box (width 1 cm, length 8 cm, height 12 cm) to be separated from the anode. An aqueous solution of halide and a polyhalogenated lower hydrocarbon were placed in the beaker, and an aqueous solution of halide was placed in the ceramic box.

Example 1 Ethyl lactate 25.0 g (212 mmol), chloroform 18
7.5 ml, 8.1% sodium bromide (188 mmol) -18.8
% Aqueous sodium dihydrogen phosphate solution (375 mmol) 187.
Put 5g into the above equipment, 1A (35.9mA / cm ² )
In the water bath while stirring with a magnetic stirrer,
After energizing 4.8 F / mol (27.5 hours) at a temperature of 20 to 30 ° C., the energization was stopped. The voltage at this time was 5V.

The resulting reaction mixture was separated, the aqueous layer was extracted with chloroform, the aqueous layer was combined with the oil layer, and the whole oil layer was washed with a 10% aqueous sodium thiosulfate solution, 5% sodium carbonate and saturated brine in this order. After the extract was dried over anhydrous magnesium sulfate, the filtrate was concentrated and further distilled under reduced pressure.
14.8 g of ethyl pyruvate was obtained. Yield 60%, boiling point 1
44 ° C, refractive index (sodium D line, 20 ° C) 1.41.

Example 2 25.0 g (212 mmol) of ethyl lactate, ruthenium dioxide
1.2 g (9 mmol), chloroform 187.5 ml, 8.1% sodium bromide (188 mmol) -18.8% sodium dihydrogen phosphate aqueous solution (375 mmol) 187.5 ml were put in the above-mentioned apparatus, and 1A (35.5. 9 mA / cm ² ) current is applied,
While stirring with a magnetic stirrer, in a water bath at 20-30 ° C 3.
After energizing 0 F / mol (17 hours), energizing was stopped.
The voltage at this time was 5V.

After ruthenium dioxide was filtered off from the obtained reaction mixture, the layers were separated, and the aqueous layer was extracted with chloroform.
The oil layer was combined with the oil layer, and the whole oil layer was washed in this order with a 10% aqueous sodium thiosulfate solution, 5% sodium carbonate, and saturated saline. The extract was dried over anhydrous magnesium sulfate, the filtrate was concentrated, and further distilled under reduced pressure to obtain ethyl pyruvate 1
4.3 g was obtained. Yield 58%, boiling point 144 ° C, refractive index (sodium D line, 20 ° C) 1.41.

Examples 3 to 6 In Example 1, instead of sodium bromide, equimolar amounts of various halides shown in Table 1 were used. The reaction conditions and the results are shown in Table 1.

[0025]

[Table 1]

Examples 7 to 9 In Example 2, instead of chloroform, various polyhalogenated lower hydrocarbons as shown in Table 2 were used in equal volumes. The reaction conditions and the results are shown in Table 2.

[0027]

[Table 2]

[0028]

According to the method of the present invention, a ruthenium compound is preferably contained in a mixed solution of an aqueous solution of a halide and a polyhalogenated lower hydrocarbon as described above, and an α-hydroxy acid ester is dispersed therein. Then, the α-hydroxy acid ester can be electrochemically oxidized by applying an electric current to industrially advantageously and easily obtain the α-keto acid ester. Therefore, the method of the present invention is
It is possible to stably supply a high-quality α-keto acid ester, which is in increasing demand for intermediates, fragrances, and other fine chemicals fields.

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Claims (3)

[Claims] 1. A mixture of an aqueous solution of at least one halide selected from the group consisting of alkali metal halides, onium halide salts and alkaline earth metal halides and a polyhalogenated lower hydrocarbon is added to an α-hydroxy acid. Α- characterized by dispersing the ester and applying electricity
Method for producing keto acid ester. 2. The method for producing an α-keto acid ester according to claim 1, wherein the mixed solution contains a ruthenium compound. 3. The method for producing an α-keto acid ester according to claim 1, wherein the aqueous solution of the halide contains a pH buffering agent.