JP2009057369A - Process for producing substituted chloromethane compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a process which can industrially more advantageously produce a chloromethane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group or an arylcarbonyl group. <P>SOLUTION: The process for producing a substituted chloromethane compound (for example, 2-chloro-3,5-pentanedione) represented by formula (2) (wherein E<SP>1</SP>to E<SP>3</SP>are each an alkoxycarbonyl group which may be substituted, an alkylcarbonyl group which may be substituted, an arylcarbonyl group which may be substituted or hydrogen) comprises reacting a group 6 element metal or a group 6 element compound with hydrogen peroxide to prepare a group 6 element oxide and then reacting a substituted methane compound (for example, acetylacetone) with hydrogen peroxide and a metal chloride in the presence of the group 6 element oxide and a phosphoric acid salt. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing a chloromethane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group or an arylcarbonyl group.

  Examples of the method for producing a chloromethane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group or an arylcarbonyl group include, for example, a methane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group or an arylcarbonyl group, hydrogen peroxide and hydrogen chloride. Or a method of reacting a metal halide with a methane compound substituted with a group similar to the above in the presence of hydrogen peroxide and an acid (for example, see Patent Document 2). See.) Is known. However, the former method uses hydrogen chloride, and as an industrial production method, development of a production method that can be chlorinated using a chlorinated product that is easier to handle has been demanded. Although the latter method is a halogenation method using a halide, only examples of bromination are described in the examples, and when applied to chlorination reaction, it is industrially satisfactory in terms of yield. It wasn't possible.

Japanese Patent Laid-Open No. 2002-37148 JP 2006-111595 A

  Therefore, the present inventor has intensively studied to develop a method capable of producing a chloromethane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group, or an arylcarbonyl group more advantageously industrially. A Group 6 element oxide is reacted with hydrogen peroxide to prepare a Group 6 element oxide, and then in the presence of the Group 6 element oxide and phosphate, the corresponding substituted methane compound and hydrogen peroxide It has been found that by reacting with a metal chlorinated product, the desired substituted chloromethane compound can be easily produced, and the present invention has been achieved.

（式中、Ｅ^１〜Ｅ^３は、それぞれ同一または相異なって、置換されていてもよいアルコキシカルボニル基、置換されていてもよいアルキルカルボニル基、置換されていてもよいアリールカルボニル基または水素原子を表す。ただし、Ｅ^１〜Ｅ^３のうち２つ以上が同時に水素原子であることはない。）
で示される置換メタン化合物と過酸化水素と金属塩素化物とを反応させる式（２）

（式中、Ｅ^１〜Ｅ^３は、それぞれ上記と同一の意味を表す。）
で示される置換クロルメタン化合物の製造方法を提供するものである。 That is, the present invention prepares a Group 6 element oxide by reacting a Group 6 element metal or a Group 6 element compound and hydrogen peroxide, and then the Group 6 element oxide and phosphate In the presence, formula (1)

(In the formula, E ^{1 to} E ³ are the same or different and each represents an optionally substituted alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group or a hydrogen atom. However, two or more of E ^{1 to} E ³ are not hydrogen atoms at the same time.)
Formula (2) in which a substituted methane compound represented by formula (2) is reacted with hydrogen peroxide and a metal chloride.

(In the formula, E ^{1 to} E ³ each have the same meaning as described above.)
The manufacturing method of the substituted chloromethane compound shown by this is provided.

  According to the present invention, a chloromethane compound substituted with an alkoxycarbonyl group, an alkylcarbonyl group, or an arylcarbonyl group can be produced using a chlorinated product that is relatively easy to handle, which is industrially advantageous. Moreover, since the reaction under acidic conditions can be avoided, it is particularly advantageous when producing a chloromethane compound having a substituent active in acid.

  First, the substituted methane compound represented by the above formula (1) (hereinafter abbreviated as substituted methane compound (1)) will be described.

Among the substituents represented by E ^{1 to} E ³ in the formula (1), examples of the alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, and pentyl. Examples thereof include linear, branched or cyclic alkoxycarbonyl groups having 2 to 20 carbon atoms such as oxycarbonyl group, hexyloxycarbonyl group, dodecyloxycarbonyl group, octadecyloxycarbonyl group and cyclohexyloxycarbonyl group. Examples of the group which may be substituted on these alkoxycarbonyl groups include, for example, halogen atoms such as fluorine atoms; alkoxy groups such as methoxy groups and ethoxy groups; alkylcarbonyl groups such as acetyl groups and propionyl groups; benzoyl groups and the like Arylcarbonyl groups such as methoxycarbonyl group and ethoxycarbonyl group; aryl groups such as phenyl group and naphthyl group; aryloxy groups such as phenoxy group, 1-naphthoxy group and 2-naphthoxy group; . Specific examples of the alkoxycarbonyl group substituted with such a group include a phenylmethoxycarbonyl group and a trifluoromethoxycarbonyl group.

  As the alkylcarbonyl group, for example, linear, branched chain such as acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, hexanoyl group, decanoyl group, lauroyl group, palmitoyl group, stearoyl group, cyclohexanecarbonyl group, etc. Or a cyclic | annular C2-C20 alkylcarbonyl group is mentioned. Examples of the group which may be substituted on these alkylcarbonyl groups include, for example, halogen atoms such as fluorine atoms; alkoxy groups such as methoxy groups and ethoxy groups; alkylcarbonyl groups such as acetyl groups and propionyl groups; benzoyl groups and the like Arylcarbonyl groups such as methoxycarbonyl group and ethoxycarbonyl group; aryl groups such as phenyl group and naphthyl group; aryloxy groups such as phenoxy group, 1-naphthoxy group and 2-naphthoxy group; . Specific examples of the alkylcarbonyl group substituted with such a group include a phenylacetyl group and a trifluoroacetyl group.

  Examples of the arylcarbonyl group include arylcarbonyl groups having 7 to 11 carbon atoms such as benzoyl group and naphthoyl group. Examples of the group which may be substituted on these arylcarbonyl groups include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. N-pentyl group, n-decyl group, cyclopropyl group, 2,2-dimethylcyclopropyl group, cyclopentyl group, cyclohexyl group, menthyl group, fluoromethyl group, trifluoromethyl group, methoxymethyl group, ethoxymethyl group, An optionally substituted alkyl group such as 3-oxobutyl group, methoxyethyl group, methoxycarbonylmethyl group, benzyl group; aryl group such as phenyl group, 1-naphthyl group, 2-naphthyl group; fluorine atom, chlorine atom, Halogen atoms such as bromine atom; alkoxy groups such as methoxy group and ethoxy group; acetyl group, Pioniru alkylcarbonyl group such as a methoxy group, an alkoxycarbonyl group such as methoxycarbonyl group and ethoxycarbonyl group; arylcarbonyl groups such as benzoyl group a cyano group; a nitro group; and the like. Specific examples of the arylcarbonyl group substituted with such a group include 4-methoxybenzoyl group and 2-chlorobenzoyl group.

  Examples of the substituted methane compound (1) include dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, di-n-butyl malonate, dicyclohexyl malonate, acetylacetone, 3,5-heptanedione, 2,4-heptanedione, 3,5-octanedione, 2,4-hexanedione, 4,6-nonadione, 1,3-diphenyl-1,3-propanedione, 1-phenyl-1,3-propanedione , Methyl 3-oxobutanoate, ethyl 3-oxobutanoate, ethyl 3-oxo-3-phenylpropionate and the like.

  Next, a method for preparing a Group 6 element oxide by reacting a Group 6 element metal or a Group 6 element compound with hydrogen peroxide will be described.

  Examples of the Group 6 element metal include tungsten metal and molybdenum metal. Examples of the Group 6 element compound include tungsten compounds such as tungsten boride, tungsten carbide, tungsten oxide, ammonium tungstate, and tungsten carbonyl complex; molybdenum compounds such as molybdenum boride, molybdenum oxide, molybdenum chloride, and molybdenum carbonyl complex; Etc.

  As hydrogen peroxide, an aqueous solution is usually used. The hydrogen peroxide concentration in the hydrogen peroxide water is not particularly limited, but is practically 1 to 60% by weight in consideration of volume efficiency, safety and the like. A commercially available product 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 for the Group 6 element oxide preparation is usually 3 mol times or more, preferably 5 mol times or more, relative to the Group 6 element metal or Group 6 element compound, and the upper limit is Not particularly.

  The Group 6 element oxide is usually prepared in the presence of water.

  The Group 6 element oxide is usually prepared by mixing and contacting a Group 6 element metal or a Group 6 element compound and hydrogen peroxide, and in order to further improve the contact efficiency, It is preferable to carry out the reaction with stirring so that the Group 6 element metal or the Group 6 element compound is sufficiently dispersed in the Group Element Oxide Preparation Solution. In addition, for example, it is possible to increase the contact efficiency between the Group 6 element metal or the Group 6 element compound and hydrogen peroxide, and to make the control during the preparation of the Group 6 element oxide easier. It is preferable to use a group element metal or a group 6 element compound or a group 6 element metal or a group 6 element compound having a small particle diameter.

  The preparation temperature of the Group 6 element oxide is usually −10 to 100 ° C.

  By reacting a Group 6 element metal or Group 6 element compound and hydrogen peroxide in water, an organic solvent or a mixed solvent of an organic solvent and water, a Group 6 element metal or a Group 6 element compound is reacted. It is possible to prepare a homogeneous solution or suspension containing a Group 6 element oxide by dissolving all or a part of it, but the Group 6 element oxide is removed from the preparation solution by, for example, concentration treatment The substituted methane compound (1), hydrogen peroxide and a metal chlorinated product may be used for the reaction, or the prepared solution may be used as it is as a catalyst. When the preparation liquid is used as a catalyst as it is, the amount of hydrogen peroxide to be reacted with the substituted methane compound (1) and the metal chlorinated compound may be determined in consideration of the amount of hydrogen peroxide in the preparation liquid.

  In addition, a Group 6 element metal or a Group 6 element compound, a phosphate, a substituted methane compound (1), hydrogen peroxide, and a metal chlorinated product are contacted and mixed to prepare a Group 6 element oxide preparation operation; Alternatively, the reaction of the substituted methane compound (1), hydrogen peroxide, and metal chloride may be performed simultaneously.

  Next, the substituted methane compound (1) is reacted with hydrogen peroxide and a metal chlorinated compound in the presence of the Group 6 element oxide and phosphate prepared above, and is represented by the above formula (2). A method for producing a substituted chloromethane compound (hereinafter abbreviated as substituted chloromethane compound (2)) will be described.

  The use amount of the Group 6 element compound is usually 0.001 mol times or more with respect to the substituted methane compound (1), and there is no particular upper limit thereof. It is 1 mol times or less with respect to an active methylene compound (1).

  As hydrogen peroxide, an aqueous solution is usually used. The hydrogen peroxide concentration in the hydrogen peroxide water is not particularly limited, but is practically 1 to 60% by weight in consideration of volume efficiency, safety and the like. A commercially available product 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 the substituted methane compound (1), and there is no particular upper limit on the amount used, but considering the economic aspect, the substitution is practical. It is 20 mol times or less with respect to a methane compound (1).

  Examples of the metal chlorinated material include alkali metal chlorinated materials such as lithium chloride, sodium chloride, and potassium chloride; alkaline earth metal chlorinated materials such as magnesium chloride, calcium chloride, and barium chloride. Alkali metal chlorinated compounds are preferable, and potassium chloride is more preferable.

  The amount of metal chlorinated compound used is usually 1 mol times or more with respect to the substituted methane compound (1), and there is no particular upper limit of the amount used, but considering the economic aspect, the substitution is practical. It is 5 mol times or less with respect to a methane compound (1).

  Any phosphate can be used without particular limitation as long as it exhibits a buffering action. Examples of the phosphate include alkali metal phosphates such as trisodium phosphate, tripotassium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate; And alkaline earth metal phosphates such as magnesium pyrophosphate and calcium phosphate. Alkali metal phosphates are preferred from the standpoint of reactivity, and hydrogen phosphate dialkali metal salts (disodium hydrogen phosphate, dipotassium hydrogen phosphate, etc.) or alkali metal dihydrogen phosphates (sodium dihydrogen phosphate, phosphorus More preferred are potassium dihydrogen acid and the like.

  The amount of phosphate used is usually 0.1 mol times or more with respect to the substituted methane compound (1), and there is no particular upper limit. However, considering economic aspects, the substituted methane is practically used. It is 5 mol times or less with respect to a compound (1).

  This reaction is usually carried out in the presence of water. The water may be water contained in hydrogen peroxide, may be water used for the preparation of the Group 6 element oxide, or may be water used in addition to them. .

  The amount of water used is not particularly limited, but is practically 100 weight times or less with respect to the substituted methane compound (1) in consideration of volumetric efficiency and the like.

  The reaction temperature is usually in the range of 0 to 100 ° C.

  The mixing order of the reaction reagents is not particularly limited when mixing at a reaction temperature or lower. When mixing under reaction temperature conditions, it is preferable to add hydrogen peroxide to the mixture of Group 6 element oxide, active methylene compound (1) and metal chlorinated compound in which phosphate coexists.

  This reaction may be carried out under normal pressure conditions or under pressurized conditions. 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, NMR, IR and the like.

  The mixture after the reaction is subjected to, for example, crystallization treatment or distillation treatment, or if necessary, extraction treatment is performed by adding water and / or water-insoluble organic solvent, and the resulting organic layer is concentrated. The substituted chloromethane compound (2) can be taken out. The extracted substituted chloromethane compound (2) may be further purified, for example, by means such as distillation or column chromatography.

  Here, examples of the organic solvent insoluble in water include aromatic hydrocarbon solvents such as toluene, xylene and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane and heptane; halogenated carbonization such as dichloromethane, dichloroethane and chloroform. Hydrogen solvents; ether solvents such as diethyl ether and methyl tert-butyl ether; ester solvents such as ethyl acetate;

  Examples of the substituted chloromethane compound (2) thus obtained include dimethyl 2-chloromalonate, diethyl 2-chloromalonate, di-n-propyl 2-chloromalonate, diisopropyl 2-chloromalonate, dichloro2-chloromalonate, and the like. n-butyl, 2-cyclohexylmalonate dicyclohexyl, 3-chloro-2,4-pentanedione, 4-chloro-3,5-heptanedione, 3-chloro-2,4-heptanedione, 4-chloro-3, 5-octanedione, 3-chloro-2,4-hexanedione, 5-chloro-4,6-nonadione, 2-chloro-1,3-diphenyl-1,3-propanedione, 2-chloro-1-phenyl -1,3-propanedione, methyl 2-chloro-3-oxobutanoate, ethyl 2-chloro-3-oxobutanoate, 2-chloro-3-oxy 3-phenylpropionic acid ethyl and the like.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by these Examples.

Example 1
When 50 mg of tungsten metal and 300 mg of 30 wt% hydrogen peroxide water were added to a 50 mL flask equipped with a reflux condenser and stirred at room temperature for 30 minutes, a colorless and transparent liquid mixture was obtained. 1 g of water, 200 mg of potassium dihydrogen phosphate, 200 mg of acetylacetone and 600 mg of potassium chloride were added to the mixture, and the temperature was raised to 40 ° C. While stirring the resulting mixture at the same temperature, 2 g of 30% by weight hydrogen peroxide was added dropwise over 1 hour. After completion of the dropwise addition, the obtained mixture was further stirred at the same temperature for 4 hours. After cooling the reaction mixture to room temperature, 10 g of ethyl acetate and 5 g of water were added thereto and stirred and allowed to stand to separate the mixture into two layers. When the upper layer was analyzed by gas chromatography (internal standard method), the conversion of acetylacetone was 50% and the selectivity for 2-chloro-3,5-pentanedione was 98%.

Example 2
When 50 mg of tungsten metal and 300 mg of 30 wt% hydrogen peroxide water were added to a 50 mL flask equipped with a reflux condenser and stirred at room temperature for 30 minutes, a colorless and transparent liquid mixture was obtained. 1 g of water, 200 mg of potassium dihydrogen phosphate, 260 mg of ethyl 3-oxobutanoate and 600 mg of potassium chloride were added to the mixture. While stirring the resulting mixture at room temperature, 3 g of 30% by weight hydrogen peroxide was added dropwise over 1 hour. After completion of the dropwise addition, the obtained mixture was further stirred at room temperature for 5 hours. When 10 g of ethyl acetate and 5 g of water were added to the mixture after completion of the reaction and stirred and allowed to stand, the mixture separated into two layers. When the upper layer was analyzed by gas chromatography (internal standard method), the conversion of ethyl 3-oxobutanoate was 35%, and the selectivity for ethyl 2-chloro-3-oxobutanoate was 63%.

Comparative Example 1: Chlorination reaction in the absence of Group 6 element oxide (Comparison with Example 1)
To a 50 mL flask equipped with a reflux condenser, 1 g of water, 200 mg of potassium dihydrogen phosphate, 200 mg of acetylacetone, and 600 mg of potassium chloride were added, and the temperature was raised to 40 ° C. While stirring the resulting mixture at the same temperature, 2 g of 30% by weight hydrogen peroxide was added dropwise over 1 hour. After completion of the dropwise addition, the obtained mixture was further stirred at the same temperature for 4 hours. After cooling the reaction mixture to room temperature, 10 g of ethyl acetate and 5 g of water were added thereto and stirred and allowed to stand to separate the mixture into two layers. When the upper layer was analyzed by gas chromatography (internal standard method), the conversion of acetylacetone was 10% and the selectivity for 2-chloro-3,5-pentanedione was 0%.

Comparative Example 2: Chlorination reaction in the absence of phosphate and in the presence of acid (chlorination by reaction described in JP-A-2006-111595)
To a 50 mL flask equipped with a reflux condenser, 200 mg of acetylacetone, 1.0 g of 30 wt% potassium chloride aqueous solution, 450 mg of 30 wt% hydrogen peroxide solution, 1.96 g of 10 wt% sulfuric acid were added and stirred at room temperature for 4 hours. After cooling the reaction mixture to room temperature, 10 g of ethyl acetate and 5 g of water were added thereto and stirred and allowed to stand to separate the mixture into two layers. When the upper layer was analyzed by gas chromatography (internal standard method), the conversion of acetylacetone was 5% and the selectivity for 2-chloro-3,5-pentanedione was 80%.

  Substituted chloromethane compounds are important compounds as various chemical products such as medical pesticides and fragrances, and synthetic intermediates thereof (for example, J. Org. Chem., 60, 3074 (1995) and Bioorganic & Medicinal Chem). Lett., 14, 2245 (2004)), according to the present invention, these compounds can be produced using chlorinated products that are easy to handle.

Claims (4)

A Group 6 element oxide is prepared by reacting a Group 6 element metal or a Group 6 element compound with hydrogen peroxide, and then, in the presence of the Group 6 element oxide and phosphate, the formula ( 1)

(In the formula, E ^{1 to} E ³ are the same or different and each represents an optionally substituted alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group or a hydrogen atom. However, two or more of E ^{1 to} E ³ are not hydrogen atoms at the same time.)
Formula (2) in which a substituted methane compound represented by formula (2) is reacted with hydrogen peroxide and a metal chloride.

(In the formula, E ^{1 to} E ³ each have the same meaning as described above.)
The manufacturing method of the substituted chloromethane compound shown by these. The production method according to claim 1, wherein the phosphate is an alkali metal phosphate or an alkaline earth metal phosphate. The production method according to claim 1, wherein the phosphate is a dialkali metal hydrogen phosphate or an alkali metal dihydrogen phosphate. The manufacturing method according to any one of claims 1 to 3, wherein the metal chloride is an alkali metal chloride or an alkaline earth metal chloride.