JP2005281282A - Method for producing pyruvic ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing pyruvic ester by hydrogen peroxide oxidation using a transition metal complex catalyst of methacrylic acid ester, wherein separation/aftertreatment of the transition metal catalyst after the reaction is simple and the catalyst can be reused. <P>SOLUTION: The method for producing pyruvic ester comprises reacting hydrogen peroxide with methacrylic ester represented by formula (1) (wherein, R is a 1-4C alkyl) to produce pyruvic ester represented by formula (2) (wherein, R is the same as the above-mentioned), wherein, the reaction is performed by using a transition metal complex having a fluorinated organic ligand as a catalyst and using a fluoro-organic solvent and a nitrile solvent as the solvent, after reaction, separating the fluoro-organic solvent phase by liquid separation, and the transition metal complex catalyst comprising fluorinated organic ligand and contained in the fluoro-organic solvent phase is recycled. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method for producing pyruvic acid ester by oxidizing hydrogen peroxide with methacrylic acid ester as an oxidizing agent (hereinafter referred to as hydrogen peroxide oxidation) in the presence of an organic complex catalyst and an organic solvent.

  Pyruvate is an important compound as a raw material for medical and agricultural chemicals. Further, pyruvic acid obtained by hydrolyzing the pyruvic acid ester is also used as a raw material for various medical and agricultural chemicals.

  Examples of uses of pyruvic acid ester and pyruvic acid include amino acids such as L-tryptophan, L-cysteine, L-tyrosine, and L-doper, quinophene, calcium isoniazid pyruvate, and the like. In the plastics industry, textile industry, adhesives field, etc., they are used as intermediates for synthesizing monomers such as α-cyanoacrylate and α-acyloxyacrylate. Furthermore, application development as a synthetic raw material for fragrances and agricultural chemicals is also underway.

Conventionally, in a method for producing pyruvate by oxidation of methacrylic acid ester with hydrogen peroxide, the oxidation has been performed using an organic complex catalyst containing chromium or vanadium in order to improve the yield. . (See Patent Document 1 and Non-Patent Document 1)
JP 6-37428 Chemistry Letters, 99, 1989

  However, these methods are economically disadvantageous because they cannot be recycled despite the high cost of organic complex catalysts, and are not necessarily industrially advantageous methods.

  The present invention relates to a method for producing pyruvic acid ester by oxidation of hydrogen peroxide with methacrylic acid ester using an organic complex catalyst, in which separation of organic complex catalyst after completion of reaction is simple, and organic complex catalyst after completion of reaction It is an object of the present invention to provide a method for producing a pyruvate that can be easily recycled.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors used a fluorine-based organic solvent and a nitrile-based solvent as the organic solvent for the method for producing pyruvate by hydrogen peroxide oxidation of a methacrylate. When the reaction is performed using a transition metal complex catalyst containing a fluorinated organic ligand as a two-phase system and an organic complex catalyst, the transition metal complex catalyst is retained in the fluorine-based organic solvent phase, and the product It was found that the transition metal complex catalyst and the product can be separated by a simple operation such as liquid separation after being held in the pyruvate nitrile solvent, and the pyruvate can be produced in a good yield. . Furthermore, if the fluorine-based organic solvent phase containing the separated transition metal complex catalyst is reacted as it is by adding new methacrylic acid ester, hydrogen peroxide and nitrile solvent, pyruvic acid ester can be produced and efficient catalyst recycling is possible. Found that it can be used.

  That is, the present invention provides hydrogen peroxide and formula (1) in the presence of an organic complex catalyst and an organic solvent:

（式中、Ｒは炭素数１〜４のアルキル基を示す。）で表されるメタクリル酸エステルとを反応させて、式（２）：

(Wherein, R represents an alkyl group having 1 to 4 carbon atoms) is reacted with a methacrylic acid ester represented by the formula (2):

（式中、Ｒは上記に同じ。）で表されるピルビン酸エステルを製造するにあたり、有機錯体触媒および有機溶媒としてそれぞれフッ素化された有機配位子をもつ遷移金属錯体およびフッ素系有機溶媒とニトリル系溶媒を用いることを特徴とするピルビン酸エステルの製造方法に関する。

(Wherein R is the same as above), a transition metal complex having a fluorinated organic ligand and a fluorinated organic solvent as an organic complex catalyst and an organic solvent, respectively, The present invention relates to a method for producing pyruvate characterized by using a nitrile solvent.

  According to the method of the present invention, after the reaction, the fluorinated organic solvent phase is separated by liquid separation, and the transition metal complex catalyst having the fluorinated organic ligand contained in the solvent phase can be used for the next reaction. Since the expensive organic complex catalyst can be recycled and pyruvate can be produced at low cost, the method of the present invention has great industrial value.

The present invention will be described in detail below.
In the formulas (1) and (2), examples of the alkyl group represented by R include a linear or branched alkyl group having 1 to 4 carbon atoms, specifically, a methyl group, an ethyl group, n Examples include -propyl group, i-propyl group, n-butyl group, i-butyl group, and t-butyl group. A methyl group or an ethyl group is preferable, and a methyl group is particularly preferable.

As the organic complex catalyst, a transition metal complex catalyst having a fluorinated organic ligand (hereinafter referred to as a transition metal complex catalyst) is used. Examples of the transition metal of the transition metal complex catalyst include Group 5 and Group 6 metals, with chromium and vanadium being particularly preferred. A fluorinated organic ligand having no particular valence is an organic ligand having at least one fluorine atom in the molecule, and can form a complex with a transition metal atom or an ion thereof. Any compound can be used as long as it is a functional compound.
As the fluorinated organic ligand, those in which the ratio of fluorine atom to hydrogen atom contained in the compound is F atom number ≧ H atom number are particularly preferable. Examples of the fluorine-substituted organic ligand include compounds of the following formulas (3) to (5).
Formula (3):

（式中、Cfは炭素数１〜１０で、フッ素化された炭化水素基を示す）
式（４）：

(In the formula, Cf represents a fluorinated hydrocarbon group having 1 to 10 carbon atoms)
Formula (4):

（式中、ｎは１〜３、ｍは１〜５の整数を示す）
式（５）
（Ｃｆ−ＳＯ_２）_２ＮＨ （５）
（式中、Cfは炭素数１〜１０のフッ素化された炭化水素基を表す）
その他にはパーフルオロアセチルアセトン、パーフルオロペンタメチルシクロペンタジエン、パーフルオロシクロペンタジエン、パーフルオロピリジン、パーフルオロテトラヒドロフラン、パーフルオロエチレンジアミンなどが挙げられるが、これらに限らない。

(Wherein n represents an integer of 1 to 3, and m represents an integer of 1 to 5)
Formula (5)
_{(Cf-SO 2) 2 NH} (5)
(In the formula, Cf represents a fluorinated hydrocarbon group having 1 to 10 carbon atoms)
Other examples include, but are not limited to, perfluoroacetylacetone, perfluoropentamethylcyclopentadiene, perfluorocyclopentadiene, perfluoropyridine, perfluorotetrahydrofuran, and perfluoroethylenediamine.

  The amount of the transition metal complex catalyst used is usually 0.0001 mol% or more with respect to 1 mol of the methacrylic acid ester, and there is no particular upper limit. However, considering the economic aspect, the methacrylic acid ester is practically used. Is 10 mol% or less. Preferably 1 mol% or less is used with respect to 1 mol of methacrylic acid ester.

  As hydrogen peroxide, an aqueous solution is usually used. Of course, an organic solvent solution of hydrogen peroxide may be used, but it is preferable to use hydrogen peroxide water because it is easier to handle. The concentration of hydrogen peroxide in the hydrogen peroxide solution or the organic solvent solution of hydrogen peroxide is not particularly limited, but is practically 1 to 60% by weight in consideration of container efficiency, safety and the like. As the hydrogen peroxide solution, a commercially available one may be used as it is or after adjusting the concentration by dilution, concentration or the like as necessary.

  The amount of hydrogen peroxide used is usually 1 mol times or more with respect to 1 mol of methacrylic acid ester, and there is no particular upper limit on the amount of use, but in consideration of economic reasons, methacrylic acid ester is practically used. It is 5 mol times or less with respect to 1 mol. Preferably it is 2-4 times mole.

In the oxidation reaction of the methacrylic acid ester of the present invention, one or more kinds of fluorinated organic solvents and one or more kinds of nitrile solvents are used as the solvent. The ratio of the amounts used of both solvents is not particularly limited. The amount of the solvent used is not particularly limited, but considering the container efficiency and the like, practically, the total amount of both solvents is usually 10 times by weight or less with respect to the methacrylic acid ester.
The fluorine-based organic solvent is a hydrocarbon, a compound in which 50% or more of hydrogen atoms contained in a molecule are replaced by fluorine atoms, or the carbon or hydrogen or fluorine atom is partially oxygen, nitrogen, A compound substituted with another halogen atom or the like is shown. More specifically, perfluoro compounds are particularly preferred because of the ease of separation of the fluorine-based organic solvent phase containing the transition metal complex catalyst and the product phase.
The properties of the fluorinated organic solvent are not particularly limited as long as they are liquid under the conditions of use, but those having 5 to 30 carbon atoms are preferred. Examples include fluorinated aliphatic hydrocarbon compounds such as perfluoropentane, perfluorohexane, and perfluorooctane, fluorinated cyclic hydrocarbon compounds such as perfluorocyclopentane and perfluoromethylcyclohexane, and fluorination of perfluorobenzene and the like. Aromatic hydrocarbon compounds, perfluoropolyethers and the like are shown. An example of the perfluoropolyether compound is shown in Formula (6).
Formula (6):

（式中でｎ、ｍは任意の整数を示す）
なお、反応時に上記の複数のフルオラス溶媒を混合して用いてもよい。

(In the formula, n and m represent arbitrary integers)
In addition, you may mix and use said several fluoro solvent at the time of reaction.

  As the nitrile solvent, compounds having a nitrile group in the molecule can be used, and specific examples include aliphatic nitrile compounds such as acetonitrile and propionitrile.

  The reaction temperature is usually 0 to 200 ° C., but preferably 30 to 150 ° C.

  This reaction is usually carried out by contacting and mixing methacrylic acid ester, hydrogen peroxide, solvent, and catalyst, but the mixing order is not particularly limited.

  This reaction can be carried out under normal pressure or under pressure. In addition, the progress of the reaction can be confirmed by ordinary analysis means such as gas chromatography, high performance liquid chromatography, thin layer chromatography, nuclear magnetic resonance spectrum analysis, infrared absorption spectrum analysis, and the like.

After completion of the reaction, the fluorine-containing organic solvent phase and the other phase are usually separated by allowing the reaction mixture to stand. By separating this phase, an organic phase or an aqueous phase containing a product or a raw material and a fluorine-based organic solvent phase containing a transition metal complex catalyst can be separated. Since the product pyruvic acid ester is contained in the separated organic phase or aqueous phase, the target pyruvic acid ester can be directly obtained by ordinary isolation and purification means such as concentration, extraction, distillation, drying, or column chromatography. can get.
The separated fluorine-based organic solvent phase can be reacted under the same conditions by adding new raw materials such as methacrylic acid ester, hydrogen peroxide and nitrile solvent, and the transition metal complex catalyst can be reused. .

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to this. The conversion rate of methyl methacrylate and the yield of methyl pyruvate shown below are calculated by measuring the reaction mixture by gas chromatography analysis using an internal standard method after completion of the reaction. The gas chromatographic analysis was performed using a Shimadzu GC-17A gas chromatograph.

Example 1
Chromium fluorous ligand _{catalyst: Cr-C 3 F 7 COCH} 2 COC 3 F 7 Preparation of commercially available _{(AcO) 7 Cr 3 (OH} ) 2 0.124g (0.206mmol) and the commercially available _C 3 _F 7 COCH ₂ 0.247 g (0.604 mmol) of COC ₃ F ₇ was dissolved in a mixed solvent of 1.5 ml of dichloroethane and 0.5 ml of acetonitrile, and kept at 50 ° C. for 4 hours. Thereafter, the reaction solution was extracted and separated three times with 2 ml of a commercially available perfluoroether solvent (6) (GALDEN-SV135 manufactured by Solvaille Solexis). This perfluoroether solvent phase was used as it was for the oxidation reaction of methyl methacrylate.

Example 2
0.46 g (4.64 mol) of methyl methacrylate, 3.66 g of a perfluoroether solvent prepared in Example 1 and containing a chromium-fluorous ligand catalyst, 2.47 g of acetonitrile, 1.83 g of 35% aqueous hydrogen peroxide The mixture was heated to 60 ° C. with stirring and reacted for 4 hours. After the reaction, the mixture was allowed to stand and separated into a perfluoroether solvent phase and an acetonitrile phase. To the separated perfluoroether solvent phase, new raw materials methyl methacrylate, hydrogen peroxide solution and acetonitrile were added, reacted under the same conditions, and recycled.
The same experiment was conducted 5 times in total, and the acetonitrile phase separated in each batch was analyzed, and the following reaction results were obtained.

Claims (4)

Hydrogen peroxide and formula (1) in the presence of an organic complex catalyst and an organic solvent:

(Wherein, R represents an alkyl group having 1 to 4 carbon atoms) is reacted with a methacrylic acid ester represented by the formula (2):

(Wherein R is the same as above), a transition metal complex having a fluorinated organic ligand and a fluorinated organic solvent as an organic complex catalyst and an organic solvent, respectively, A method for producing a pyruvate characterized by using a nitrile solvent. The method for producing pyruvate according to claim 1, wherein the nitrile solvent is acetonitrile. The method for producing pyruvate according to claim 1 or 2, wherein the methacrylate is methyl methacrylate. The method for producing a pyruvate according to claim 1, 2 or 3, wherein the transition metal complex is a chromium complex.