Production method of ethyl methyl sulfone

Abstract

To provide a novel production method of ethyl methyl sulfone.SOLUTION: A production method of ethyl methyl sulfone comprises obtaining ethyl thioacetic acid by making thioglycolic acid chemically react with an ethyl halide or diethyl sulfuric acid in the presence of an inorganic base, obtaining ethyl sulfonyl acetic acid by making the obtained ethyl thioacetic acid chemically react with hydrogen peroxide, and decarboxylating the obtained ethyl sulfonyl acetic acid.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a process for producing ethyl methyl sulfone. [Background technology]

[0002] Sulfone is a general term for compounds that are formed by binding a hydrocarbon group to a sulfuryl group. Its general formula is R-SO2-R. Sulfones are widely used in industrial fields such as pharmaceuticals, plastics, and basic organic synthesis. Sulfone compounds are generally prepared by methods such as oxidation of thioethers, oxidation of sulfides, oxidation of sulfoxides (Patent Document 1), alkylation of sulfinates, addition reaction of sulfur dioxide with conjugated alkadienes, and reaction of aromatic compounds with thionyl chloride.

[0003] Ethyl methyl sulfone is a compound consisting of a sulfuryl group with a methyl group and an ethyl group attached. Ethyl methyl sulfone is considered to be the most commonly used chemical mutagen in plant and microbial breeding. Ethyl methyl sulfone can be obtained, for example, by oxidation of ethyl methyl sulfide. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2019-520401 A Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel method for producing ethyl methyl sulfone (also known as (methanesulfonyl)ethane, (methylsulfonyl)ethane). [Means for solving the problem]

[0006] As a result of extensive investigations aimed at achieving the above object, the present invention has been completed, which includes the following aspects. [1] Chemically reacting thioglycolic acid with an ethyl halide or diethyl sulfate in the presence of an inorganic base to obtain ethylthioacetic acid; reacting the resulting ethylthioacetate with hydrogen peroxide to obtain ethylsulfonylacetate; and decarboxylating the resulting ethylsulfonylacetic acid. Method for producing ethyl methyl sulfone.

[0007] [2] A method for producing ethyl methyl sulfone, comprising decarboxylating ethylsulfonylacetic acid. [3] Chemically reacting ethylthioacetic acid with hydrogen peroxide to obtain ethylsulfonylacetic acid; and decarboxylating the resulting ethylsulfonylacetic acid. Method for producing ethyl methyl sulfone.

[0008] [4] A method for producing ethylthioacetic acid, comprising chemically reacting thioglycolic acid with an ethyl halide or diethyl sulfate in the presence of an inorganic base.

[0009] [5] A method for producing ethylsulfonylacetic acid, comprising chemically reacting ethylthioacetic acid with hydrogen peroxide. Effect of the Invention

[0010] According to the production process of the present invention, ethylthioacetate, ethylsulfonylacetate, and ethylmethylsulfone can be obtained in high yields. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] One embodiment of the production method of the present invention includes obtaining ethylthioacetic acid from thioglycolic acid, obtaining ethylsulfonylacetic acid from ethylthioacetic acid, and obtaining ethylmethylsulfone from ethylsulfonylacetic acid. Another embodiment of the process of the present invention involves obtaining ethyl methyl sulfone from ethylsulfonylacetic acid. Another embodiment of the process of the present invention includes obtaining ethylsulfonylacetic acid from ethylthioacetic acid, and obtaining ethylmethylsulfone from ethylsulfonylacetic acid.

[0012] [Conversion of thioglycolic acid to ethylthioacetate (chemical reaction I)] TIFF2025017012000001.tif2687

[0013] The conversion of thioglycolic acid to ethylthioacetate involves chemically reacting thioglycolic acid with an ethyl halide or diethyl sulfate in the presence of an inorganic base. Thioglycolic acid is a known substance and can be obtained by chemically reacting monochloroacetic acid with hydrogen sulfide in the presence of a tertiary amine under pressure in a solvent. The ethylthioacetate obtained in chemical reaction I is a known substance and is useful as a raw material for organic synthesis.

[0014] Examples of the inorganic base present in chemical reaction I include sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, etc. The amount of the inorganic base used is, for example, 2.0 to 5.0 mol, preferably 2.0 to 3.0 mol, relative to 1 mol of thioglycolic acid.

[0015] Examples of the ethyl halide used in Chemical Reaction I include ethyl chloride, ethyl bromide, ethyl iodide, etc. The amount of the ethyl halide or diethyl sulfate used is, for example, 1.0 to 5.0 mol, preferably 1.0 to 1.2 mol, per 1 mol of thioglycolic acid.

[0016] Chemical reaction I can be carried out in a liquid phase. In consideration of operability, chemical reaction I is preferably carried out in water. The amount of water used is preferably 2 to 500 parts by weight per part by weight of thioglycolic acid.

[0017] The order of addition of thioglycolic acid, ethyl halide or diethyl sulfate, inorganic base, and water to the reaction site in chemical reaction I is not particularly limited.

[0018] One embodiment of chemical reaction I involves dissolving an inorganic base in water, adding thioglycolic acid thereto to obtain a mixture, and adding an ethyl halide or diethyl sulfate to the mixture to complete the chemical reaction. Each substance may be added to the reaction site all at once or in small amounts gradually, but preferably in small amounts gradually. Dropping is suitable for gradually adding small amounts. Each substance is preferably added to the reaction site while stirring. The temperature when each substance is added (dropped) is not particularly limited, but is preferably 0°C to room temperature. The temperature when chemical reaction I is carried out is not particularly limited, and may be the temperature at the time of addition or a higher temperature. For example, it is 0°C to 60°C, preferably 30 to 50°C. The pressure when chemical reaction I is carried out is, for example, 0.1 to 1 MPa, preferably 0.1 to 0.5 MPa, more preferably 0.1 MPa. The time spent on chemical reaction I is not particularly limited, and is, for example, 0.5 hours to 24 hours. Chemical reaction I is preferably carried out under an inert gas atmosphere.

[0019] After completion of chemical reaction I, the product may be extracted with an organic solvent, and the resulting organic layer may be dried, concentrated, or otherwise treated. If necessary, the product of chemical reaction I may be purified by recrystallization, chromatography, or other procedures.

[0020] [Conversion of ethylthioacetate to ethylsulfonylacetate (chemical reaction II)] TIFF2025017012000002.tif27103

[0021] The conversion of ethylthioacetate to ethylsulfonylacetate involves chemically reacting ethylthioacetate with hydrogen peroxide. The ethylsulfonylacetate obtained in Chemical Reaction II is a known substance and is useful as a raw material for organic synthesis. The hydrogen peroxide used in the chemical reaction II may be a commercially available aqueous solution of hydrogen peroxide with a concentration of 30 w / v %. The amount of hydrogen peroxide used is preferably 2 to 3 moles per mole of ethylthioacetate.

[0022] In order to promote the chemical reaction II, it is preferable to use a transition metal compound. The transition metal compound that can be used is not particularly limited as long as it promotes the reaction. For example, oxides of transition metals such as titanium oxide, manganese oxide, iron oxide, copper oxide, molybdenum oxide, cerium oxide, and tungsten oxide can be mentioned. Specifically, titanium oxide (IV), manganese dioxide, iron oxide (II), iron oxide (III), copper oxide (I), copper oxide (II), molybdenum oxide (VI), cerium oxide (IV), and tungsten oxide (VI) can be mentioned. As another example, salts of transition metal oxides and their hydrates can be mentioned. These can be used alone or in combination. As the transition metal compound to be used, "sodium tungstate dihydrate" is preferable. The amount of the transition metal compound used is, for example, preferably 0.001 to 0.2 mol per 1 mol of ethylthioacetic acid.

[0023] Chemical reaction II is preferably carried out in water. The water is preferably in the range of neutral to alkaline. The amount of water used is preferably 1 to 100 parts by weight per 1 part by weight of ethylthioacetic acid. In order to adjust the pH of the reaction field, it is preferable to use an inorganic base. Examples of inorganic bases that can be used include sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium hydride, and potassium hydride. When chemical reaction II is carried out subsequent to chemical reaction I, the amount of the inorganic base used is, for example, 0.3 to 1.0 mol, and preferably 0.4 to 0.6 mol, per 1 mol of thioglycolic acid. The amount of the inorganic base used is, for example, 0.3 to 1.0 mol, preferably 0.4 to 0.6 mol, relative to 1 mol of ethylthioacetic acid.

[0024] One embodiment of chemical reaction II includes dissolving an inorganic base in water, further dissolving ethylthioacetate and, optionally, a transition metal compound therein to obtain a mixture, and adding aqueous hydrogen peroxide to the mixture to complete the chemical reaction. The hydrogen peroxide is preferably added to the reaction field in small amounts gradually. The dropwise addition is suitable for adding a small amount gradually. The hydrogen peroxide is preferably added to the reaction field while stirring. The temperature when each substance is added (dropped) is not particularly limited, but may be room temperature. The temperature when chemical reaction II is carried out is not particularly limited, and may be the temperature at the time of addition or a higher temperature. For example, it is 0°C to 60°C, preferably 30 to 50°C. The pressure when chemical reaction II is carried out is, for example, 0.1 to 1 MPa, preferably 0.1 to 0.5 MPa, more preferably 0.1 MPa. The time spent on chemical reaction II is not particularly limited, and is, for example, 0.5 hours to 24 hours. Chemical reaction II is preferably carried out under an inert gas atmosphere.

[0025] After completion of chemical reaction II, the product may be extracted with an organic solvent, and the organic layer obtained may be dried, concentrated, etc. If necessary, the product of chemical reaction II may be purified by recrystallization, chromatography, or other procedures.

[0026] [Conversion of ethylsulfonylacetic acid to ethyl methylsulfone (chemical reaction III)] TIFF2025017012000003.tif2895

[0027] Conversion of ethylsulfonylacetic acid to ethyl methylsulfone involves decarboxylation of the ethylsulfonylacetic acid. In the chemical reaction III, the decarboxylation can be carried out by a method similar to a known method, for example, a method in which the decarboxylation is carried out in the presence of an acid can be mentioned.

[0028] Examples of the acid used in the chemical reaction III include carboxylic acids such as acetic acid, formic acid, oxalic acid, benzoic acid, and 4-chlorobenzoic acid; phosphoric acid; sulfonic acids such as methanesulfonic acid, 4-toluenesulfonic acid monohydrate, and trifluoromethanesulfonic acid; hydrogen halides such as hydrogen chloride, hydrogen bromide, hydrogen iodide, and hydrogen fluoride; sulfuric acid, nitric acid, and tetrafluoroboric acid. The amount of the acid used in the chemical reaction III is, for example, 0.5 to 5 moles per mole of ethylsulfonylacetic acid.

[0029] Chemical reaction III is preferably carried out in a solvent. For example, decarboxylation can be carried out by dropping an acid into a mixture of ethylsulfonylacetic acid and a solvent at room temperature while stirring, and then heating the mixture while continuing to stir. Solvents that can be used include water, organic solvents, mixed solvents of water and organic solvents, mixed solvents of organic solvents, and the like. Examples of the organic solvent include alcohols such as methanol and ethanol; ethers such as diethyl ether, diisopropyl ether, diethylene glycol dimethyl ether (product name: diglyme), and tetrahydrofuran (abbreviation: THF); esters such as ethyl acetate; halogenated hydrocarbons such as dichloromethane, chloroform, and 1,2-dichloroethane (abbreviation: DCE); aliphatic hydrocarbons such as pentane, hexane, cyclohexane, heptane, and octane; aromatic hydrocarbons such as toluene and xylene; aprotic polar solvents such as N,N-dimethylformamide (abbreviation: DMF), N,N'-dimethylpropyleneurea (abbreviation: DMPU), and hexamethylphosphoric triamide (abbreviation: HMPA); acetonitrile; and acetic acid. The amount of the solvent used is preferably 1 to 100 parts by weight relative to 1 part by weight of ethylsulfonylacetic acid.

[0030] It is more preferable that the chemical reaction III is carried out in an acetic acid solvent. In this case, it is preferable to further add an organic acid salt such as sodium acetate, preferably an acetate salt, to the reaction site. The amount of the organic acid salt used is, for example, 0.2 to 1.0 mol, preferably 0.4 to 0.6 mol, per 1 mol of ethylsulfonylacetic acid.

[0031] The order of addition of ethylsulfonylacetic acid, an acid, and a solvent used in chemical reaction III to the reaction site is not particularly limited. One embodiment of chemical reaction III involves dissolving ethylsulfonylacetic acid in a solvent to obtain a mixture, adding an acid to the mixture, and heating to complete the decarboxylation. An embodiment using acetic acid as the solvent includes dissolving ethylsulfonylacetic acid in acetic acid to obtain a mixture, adding an organic acid salt to the mixture, and heating to complete the decarboxylation.

[0032] Each substance may be added to the reaction site all at once or in small amounts gradually, but preferably in small amounts gradually. Dropping is suitable for gradually adding small amounts. Each substance is preferably added to the reaction site while stirring. The temperature at which each substance is added (dropped) is not particularly limited and may be room temperature. The temperature during chemical reaction III is preferably carried out under heating, and is, for example, 40 to 150°C, depending on the boiling point of the solvent used. The pressure during chemical reaction III is, for example, 0.1 to 1 MPa, preferably 0.1 to 0.5 MPa, more preferably 0.1 MPa. The time spent on chemical reaction III is not particularly limited and is, for example, 0.5 hours to 24 hours. Chemical reaction III is preferably carried out under an inert gas atmosphere.

[0033] After completion of chemical reaction III, the product may be extracted with an organic solvent, and the organic layer obtained may be dried, concentrated, etc. If necessary, the product of chemical reaction III may be purified by recrystallization, chromatography, etc.

[0034] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples.

[0035] Example 1 Ethyl methyl sulfone was obtained by the following procedure. Note that two types of step 1 are described below. [Chemical Reaction I] S-Ethylation of Thioglycolic Acid with Ethyl Bromide 16.8g (0.420mol) of sodium hydroxide was dissolved in 60ml of water, followed by the addition of 18.4g (0.193mol as 96.6w%) of thioglycolic acid. The mixture was cooled to below 20℃, and 23.4g (0.215mol) of ethyl bromide was added dropwise over 10 minutes. The mixture was stirred at room temperature for 3 hours. Then, 10g of sulfuric acid was added. Extraction with methylene chloride, drying with sodium sulfate, and concentration were performed to obtain 22.55g of ethylthioacetate (NMR quantitative value 99w%, yield 96%).

[0036] Example 2 [Chemical Reaction I] S-Ethylation of Thioglycolic Acid with Diethyl Sulfate 1.60g (40.0mmol) of sodium hydroxide was dissolved in 6ml of water, followed by the addition of 1.84g (19.3mmol as 96.6w%) of thioglycolic acid. 3.39g (22.0mmol) of diethyl sulfate was added and the mixture was stirred at room temperature for 1 hour, then at 60°C for 3 hours. After cooling to room temperature, 1g of sulfuric acid was added. Extraction with methylene chloride, drying with sodium sulfate, and concentration were performed to obtain 2.12g of ethylthioacetate (NMR quantitative value 100w%, yield 91%).

[0037] Example 3 [Chemical Reaction II] Oxidation of Ethylthioacetate 2.00g (50mmol) of sodium hydroxide was dissolved in 7.2ml of water. 12.0g (100mmol) of ethylthioacetic acid and 0.33g (10mol%) of sodium tungstate dihydrate were added to this. 11.3g of 30% hydrogen peroxide was added dropwise over 30 minutes at 30°C or less. Then, 10.8g of 30% hydrogen peroxide was added dropwise over 20 minutes at 50°C or less. After the dropwise addition, the mixture was stirred at 40°C for 1.5 hours. Next, excess hydrogen peroxide was reduced with sodium bisulfite, and 5g of sulfuric acid was added. Extraction with ethyl acetate and concentration were performed to obtain 15.92g of ethylsulfonylacetic acid (NMR quantitative value 91w%, yield 95%).

[0038] Example 4 [Chemical Reaction III] Decarboxylation of Ethylsulfonylacetic Acid 9.34g (55.9 mmol) of ethylsulfonylacetic acid (91w%) was dissolved in 11 ml of acetic acid. 2.20g (50mol%) of sodium acetate was added and stirred at 140°C for 10 hours. Then, acetic acid was distilled off. Next, neutralization with aqueous sodium hydroxide solution, extraction with methylene chloride, drying with sodium sulfate, and concentration were performed to obtain 5.36g of ethyl methylsulfone (NMR quantitative value 101%, yield 89%).

[0039] As described above, the production method of the present invention makes it possible to obtain ethylthioacetic acid, ethylsulfonylacetic acid, and ethyl methylsulfone, which are useful as raw materials for organic synthesis, in high yields.

Claims

1. Chemical reaction of thioglycolic acid with an ethyl halide or diethyl sulfate in the presence of an inorganic base to obtain ethylthioacetic acid; reacting the resulting ethylthioacetate with hydrogen peroxide to obtain ethylsulfonylacetate; and decarboxylating the resulting ethylsulfonylacetic acid; Method for producing ethyl methyl sulfone.

2. A method for producing ethyl methyl sulfone, comprising decarboxylating ethylsulfonylacetic acid.

3. Chemically reacting ethylthioacetate with hydrogen peroxide to obtain ethylsulfonylacetate; and decarboxylating the resulting ethylsulfonylacetic acid; Method for producing ethyl methyl sulfone.

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