WO2013080896A1 - Method for producing 2,6-diethyl-4-methylphenylacetic acid - Google Patents

Method for producing 2,6-diethyl-4-methylphenylacetic acid Download PDF

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Publication number
WO2013080896A1
WO2013080896A1 PCT/JP2012/080401 JP2012080401W WO2013080896A1 WO 2013080896 A1 WO2013080896 A1 WO 2013080896A1 JP 2012080401 W JP2012080401 W JP 2012080401W WO 2013080896 A1 WO2013080896 A1 WO 2013080896A1
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Prior art keywords
diethyl
acid
methylphenyl
salt
ethanol
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PCT/JP2012/080401
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French (fr)
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Junichi Ishikawa
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Sumitomo Chemical Company, Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/29—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with halogen-containing compounds which may be formed in situ
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
    • C07C33/20—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part monocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/27—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids

Definitions

  • the present invention relates to a method for producing 2, 6-diethyl-4-methylphenylacetic acid.
  • 6-diethyl-4-methylphenylacetic acid is an important compound as a synthetic intermediate for a medicine and a pesticide and the like (For example, Patent document 1 and Non-patent document 1) .
  • Non-patent document 1 a production method comprising 6 steps, wherein 3 , 5-diethylphenol is used as a starting material..
  • the object of the present invention is to provide a novel method for producing 2 , 6-diethyl-4-methylphenylacetic acid.
  • the present invention includes the inventions described following [1] - [8] .
  • 2, 6-diethyl-4-methylphenylacetic acid characterized by comprising a step of reacting a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide to obtain 2- (2, 6-diethyl-4-methylphenyl) ethanol and a step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol .
  • Examples of the 2 , 6-diethyl-4-methylphenyl magnesium halide include 2, 6-diethyl-4-methylphenyl magnesium chloride, 2 , 6-diethyl-4-methylphenyl magnesium bromide and
  • the 2 , 6-diethyl-4-methylphenyl magnesium halide can be produced by a Grignard . reaction of the corresponding 2 , 6-diethyl-4-methylhalobenzene with magnesium.
  • Ethylene oxide can be produced by a known method such as an oxidation reaction of ethylene.
  • the reaction of a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is usually conducted in the presence of an organic solvent.
  • organic solvent include an ether solvent such as tetrahydrofuran and dioxane; an aromatic hydrocarbon solvent such as benzene, toluene and xylene; and a mixed solvent thereof.
  • An ether solvent is preferred, and tetrahydrofuran is more preferred.
  • the used amount of ethylene oxide is preferably in the range of from 1 to 3 mole, more preferably in the range of from 1 to 2 mole with respect to 1 mole of a 2 , 6-diethyl-4-methylphenyl magnesium halide.
  • the reaction temperature of the reaction of a 2, 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is preferably in the range of from 0 °C to 100 ° " C, ' more preferably in the range of from 0 °C to 50 °C.
  • the reaction in the presemt step is conducted by mixing a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide. While the mixing order is not limited, the mixing is preferably conducted by a method comprising blowing gaseous ethylene oxide into a 2 , 6-diethyl-4-methylphenyl magnesium halide as necessary in the presence of an organic solvent or a method comprising adding a solution containing ethylene oxide into a 2, 6-diethyl-4-methylphenyl magnesium halide.
  • the obtained 2- (2, 6-diethyl-4-methylphenyl ) ethanol may be provided to the next oxidation as the reaction mixture, and as necessary 2- (2 , 6-diethyl-4-methylphenyl ) ethanol may be isolated by an isolating operation such as washing, concentration and crystallization and then provided to the next oxidation.
  • the isolated 2- (2, 6-diethyl-4-methylphenyl ) ethanol may be provided to the next oxidation after being purified by a treatment such as rectification and recrystallization .
  • Examples of the oxidation in the present step include an oxidation conducted in the presence of a nitroxyl radical, an oxidation using cromic acid as an oxidation agent, an oxidation using potassium salt of permanganic acid as an oxidation agent and a contact oxidation using a noble metal-supported catalyst, an oxidation conducter in the presence of a nitroxyl radical is preferable.
  • An oxidation conducted in the presence of a nitroxyl radical will be illustrated in more detail below.
  • the oxidation conducted in the presence of a nitroxyl radical is conducted preferably further in the presence of a salt of a hypohalous acid and/or a salt of a halous acid, more preferably in the presence of a salt of a hypohalous acid and a salt of a halous acid.
  • the oxidation conducted in the presence of a nitroxyl radical may be carried out further in the presence of a bromide salt.
  • a bromide salt examples include lithium bromide, potassium bromide and sodium bromide.
  • nitroxyl radical examples include 2, 2, 6, 6-tetramethylpiperidine 1-oxyl (hereinafter, referred to as TEMPO in some cases) , 4-acetoamido TEMPO, 4-carboxy TEMPO, 4-amino TEMPO, 4-phosphonoxy TEMPO, 4- (2-bromoacetoamideo TEMPO, 4-hydroxy TEMPO, 4-oxy TEMPO,
  • 3-carbamoyl-2 2,5, 5-tetramethylpyrrolidin-l-oxyl and 3-carbamoyl-2 , 2,5, 5-tetramethyl-3-pyrorin-l-yloxyl .
  • Examples of the salt of a hypohalous acid include a salt of hypobromous acid such as sodium hypobromous acid; a salt of hypochlorous acid such as sodium hypochlorous acid and potassium hypochlorous acid.
  • Examples of the salt of a halous acid include a salt of bromous acid such as sodium bromous acid; a salt of chlorous acid such as sodium chlorous acid and magnesium chlorous acid.
  • the used amount of the nitroxyl radical is preferably in the range of from 0.001 to 1 mole, more preferably in the range of from 0.01 to 0.1 mole with respect to 1 mole of 2- (2, 6-diethyl-4-methylphenyl) ethanol .
  • the used amount of the salt of a hypohalous acid is preferably in the range of from 0.01 to 3 mole, more preferably in the range of from 0.1 to 1 mole with respect to 1 mole of 2- (2, 6-diethyl-4-methylphenyl) ethanol .
  • the used amount of the salt of a halous acid is preferably in the range of from 1 to 5 mole, more preferably in the range of from 1 to 2 mole with respect to 1 mole of 2- (2, e-diethyl-4-methylphenyl) ethanol.
  • the oxidation conducted in the presence of a nitroxyl radical is carried out preferably in the presence of a solvent.
  • a solvent include an aqueous solution adjusted in pH about 4-9 such as phosphate buffer and carbonate buffer; and a mixed solvent of a hydrophilic solvent such as tetrahydrofuran, dioxane and acetonitrile and the above-described aqueous solution, preferably a mixed solvent of carbonate buffer and acetonitrile.
  • the reaction temperature of the oxidation carried out in the presence of a nitroxyl radical is preferably in the range of from 0 °C to 100 °C, more preferably in the range of from 0 °C to 50 °C.
  • the oxidation conducted in the presence of a nitroxyl radical can be carried out by mixing
  • 2 6-diethyl-4-methylphenylacetoaldehide in some cases.
  • 2 , 6-diethyl-4-methylphenylacetic acid can be produced by additionally oxidizing
  • 2, 6-diethyl-4-methylphenylacetoaldehide is oxidized by reacting 2, 6-diethyl-4-methylphenylacetoaldehide with a salt of a hypohalous acid to obtain
  • the obtained 2 , 6-diethyl-4-methylphenylacetic acid as necessary can be isolated as a compound by an isolation handling such as washing, concentration and crystallization.
  • the isolated 2, 6-diethyl-4-methylphenylacetic acid may be purified by an additional treatment such as rectification and recrystallization .
  • reaction mixture after dropping was divided in 2 layers. Water (about 20 mL) was added until the reaction mixture became homogeneous solution. After that, the reaction mixture was extracted by 50 mL of chloroform, and the organic layer was dried with anhydrous magnesium sulfate, then the solvent was distilled away to obtain 0.18 g of 2, 6-diethyl-4-methylphenylacetic acid as a white crystal (yield 84 % ) .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A method for producing 2,6-diethyl-4-methylphenylacetic acid comprising a step of reacting a 2,6-diethyl-4-methylphenyl magnesium halide with ethylene oxide to obtain 2-(2,6-diethyl-4-methylphenyl) ethanol; and a step of oxidizing 2-(2,6-diethyl-4-methylphenyl) ethanol. The oxidation is conducted preferably further in the presence of a nitroxyl radical, and more preferably in the presence of a salt of a hypohalous acid and/or a salt of a halous acid.

Description

DESCRIPTION
METHOD FOR PRODUCING 2 , 6-DIETHYL-4 -METHYLPHENYLACETIC ACID
[Technical Field]
[0001]
The present invention relates to a method for producing 2, 6-diethyl-4-methylphenylacetic acid.
[Background Art]
[0002]
2 , 6-diethyl-4-methylphenylacetic acid is an important compound as a synthetic intermediate for a medicine and a pesticide and the like (For example, Patent document 1 and Non-patent document 1) . In Non-patent document 1, a production method comprising 6 steps, wherein 3 , 5-diethylphenol is used as a starting material..
[Prior art documents]
[Patent document]
[0003]·
[Patent document 1] WO 02/092606 Al
[Non-patent document]
[0004]
[Non-patent document 1] Bioorganic & Medicinal Chemistry Vol. 17 (2009), 4241-4256 [Summary of the Invention]
[Problem to be solved by the invention]
[0005]
The object of the present invention is to provide a novel method for producing 2 , 6-diethyl-4-methylphenylacetic acid.
[Means for solving problem]
[0006]
The present invention includes the inventions described following [1] - [8] .
[1] A method for producing
2, 6-diethyl-4-methylphenylacetic acid characterized by comprising a step of reacting a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide to obtain 2- (2, 6-diethyl-4-methylphenyl) ethanol and a step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol .
[2] The method according to [1], wherein the step of reacting a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is conducted in an ether solvent.
[3] The method according to [1] or [2], wherein the step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol is conducted in the presence of a nitroxyl radical compound.
[4] 'The method according to any of [1] - [3] , wherein the step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol is conducted in the presence of a salt of a hypohalous acid and/or a salt of a halous acid.
[5] The method according to any of [1] - [3] , wherein the step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol is conducted in the presence of a salt of a hypohalous acid and a salt of a halous acid.
[6] The method according to [4] or [5], wherein the salt of a hypohalous acid is a salt of a hypochlorous acid.
[7] The method according to [4] or [5], wherein the salt of a halous acid is a salt of chlorous acid.
[8] 2- (2, 6-diethyl-4-methylphenyl) ethanol.
[Effect of the invention]
[0007]
According to the present invention,
2, 6-diethyl-4-methylphenylacetic acid can be produced with shorter steps.
[Modes for Carrying Out the Invention]
[0008]
The present invention will be illustrated in detail below. First, the step of reacting a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide to obtain 2- (2, 6-diethyl-4-methylphenyl ) ethanol will be illustrated.
[0009] Examples of the 2 , 6-diethyl-4-methylphenyl magnesium halide include 2, 6-diethyl-4-methylphenyl magnesium chloride, 2 , 6-diethyl-4-methylphenyl magnesium bromide and
2 , 6-diethyl-4-methylphenyl magnesium iodide.
[0010]
The 2 , 6-diethyl-4-methylphenyl magnesium halide can be produced by a Grignard . reaction of the corresponding 2 , 6-diethyl-4-methylhalobenzene with magnesium.
[0011]
Ethylene oxide can be produced by a known method such as an oxidation reaction of ethylene.
[0012]
The reaction of a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is usually conducted in the presence of an organic solvent. Examples of the organic solvent include an ether solvent such as tetrahydrofuran and dioxane; an aromatic hydrocarbon solvent such as benzene, toluene and xylene; and a mixed solvent thereof. An ether solvent is preferred, and tetrahydrofuran is more preferred.
[0013]
The used amount of ethylene oxide is preferably in the range of from 1 to 3 mole, more preferably in the range of from 1 to 2 mole with respect to 1 mole of a 2 , 6-diethyl-4-methylphenyl magnesium halide.
[0014] The reaction temperature of the reaction of a 2, 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is preferably in the range of from 0 °C to 100 °"C,' more preferably in the range of from 0 °C to 50 °C.
[0015]
The reaction in the presemt step is conducted by mixing a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide. While the mixing order is not limited, the mixing is preferably conducted by a method comprising blowing gaseous ethylene oxide into a 2 , 6-diethyl-4-methylphenyl magnesium halide as necessary in the presence of an organic solvent or a method comprising adding a solution containing ethylene oxide into a 2, 6-diethyl-4-methylphenyl magnesium halide.
[0016]
The obtained 2- (2, 6-diethyl-4-methylphenyl ) ethanol may be provided to the next oxidation as the reaction mixture, and as necessary 2- (2 , 6-diethyl-4-methylphenyl ) ethanol may be isolated by an isolating operation such as washing, concentration and crystallization and then provided to the next oxidation. The isolated 2- (2, 6-diethyl-4-methylphenyl ) ethanol may be provided to the next oxidation after being purified by a treatment such as rectification and recrystallization .
[0017]
Next, a step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol will be illustrated.
[0018]
Examples of the oxidation in the present step include an oxidation conducted in the presence of a nitroxyl radical, an oxidation using cromic acid as an oxidation agent, an oxidation using potassium salt of permanganic acid as an oxidation agent and a contact oxidation using a noble metal-supported catalyst, an oxidation conducter in the presence of a nitroxyl radical is preferable. An oxidation conducted in the presence of a nitroxyl radical will be illustrated in more detail below.
[0019]
The oxidation conducted in the presence of a nitroxyl radical is conducted preferably further in the presence of a salt of a hypohalous acid and/or a salt of a halous acid, more preferably in the presence of a salt of a hypohalous acid and a salt of a halous acid.
[0020]
The oxidation conducted in the presence of a nitroxyl radical may be carried out further in the presence of a bromide salt. Examples of the bromide salt include lithium bromide, potassium bromide and sodium bromide.
[0021]
Examples of the nitroxyl radical include 2, 2, 6, 6-tetramethylpiperidine 1-oxyl (hereinafter, referred to as TEMPO in some cases) , 4-acetoamido TEMPO, 4-carboxy TEMPO, 4-amino TEMPO, 4-phosphonoxy TEMPO, 4- (2-bromoacetoamideo TEMPO, 4-hydroxy TEMPO, 4-oxy TEMPO,
3-carboxyl-2 , 2, 5, 5-tetramethylpyrrolidin-l-oxyl,
3-carbamoyl-2 ,2,5, 5-tetramethylpyrrolidin-l-oxyl and 3-carbamoyl-2 , 2,5, 5-tetramethyl-3-pyrorin-l-yloxyl .
[0022]
Examples of the salt of a hypohalous acid include a salt of hypobromous acid such as sodium hypobromous acid; a salt of hypochlorous acid such as sodium hypochlorous acid and potassium hypochlorous acid. Examples of the salt of a halous acid include a salt of bromous acid such as sodium bromous acid; a salt of chlorous acid such as sodium chlorous acid and magnesium chlorous acid.
[0023]
The used amount of the nitroxyl radical is preferably in the range of from 0.001 to 1 mole, more preferably in the range of from 0.01 to 0.1 mole with respect to 1 mole of 2- (2, 6-diethyl-4-methylphenyl) ethanol .
[0024]
The used amount of the salt of a hypohalous acid is preferably in the range of from 0.01 to 3 mole, more preferably in the range of from 0.1 to 1 mole with respect to 1 mole of 2- (2, 6-diethyl-4-methylphenyl) ethanol .
[0025]
The used amount of the salt of a halous acid is preferably in the range of from 1 to 5 mole, more preferably in the range of from 1 to 2 mole with respect to 1 mole of 2- (2, e-diethyl-4-methylphenyl) ethanol."
[0026]
The oxidation conducted in the presence of a nitroxyl radical is carried out preferably in the presence of a solvent. Examples of the solvent include an aqueous solution adjusted in pH about 4-9 such as phosphate buffer and carbonate buffer; and a mixed solvent of a hydrophilic solvent such as tetrahydrofuran, dioxane and acetonitrile and the above-described aqueous solution, preferably a mixed solvent of carbonate buffer and acetonitrile.
[0027]
The reaction temperature of the oxidation carried out in the presence of a nitroxyl radical is preferably in the range of from 0 °C to 100 °C, more preferably in the range of from 0 °C to 50 °C.
[0028]
The oxidation conducted in the presence of a nitroxyl radical can be carried out by mixing
2- (2, 6-diethyl-4-methylphenyl) ethanol, a nitroxyl radical and a salt of a hypohalous acid and/or a salt of a halous acid in any order as necessary in the presence of a solvent. It is preferred that a salt of a hypohalous acid is added to a mixture of 2- (2, 6-diethyl-4-methylphenyl) ethanol and a nitroxyl radical to react, and then a salt of a halous acid is added thereto react.
[0029]
While usually 2 , 6-diethyl-4-methylphenylacetic acid is obtained by the oxidation in the present step, some or all of 2 , 6-diethyl-4-methylphenylacetic acid becomes
2 , 6-diethyl-4-methylphenylacetoaldehide in some cases. In that case, 2 , 6-diethyl-4-methylphenylacetic acid can be produced by additionally oxidizing
2, 6-diethyl-4-methylphenylacetoaldehide . For example,
2, 6-diethyl-4-methylphenylacetoaldehide is oxidized by reacting 2, 6-diethyl-4-methylphenylacetoaldehide with a salt of a hypohalous acid to obtain
2, 6-diethyl-4-methylphenylacetic acid.
[0030]
The obtained 2 , 6-diethyl-4-methylphenylacetic acid as necessary can be isolated as a compound by an isolation handling such as washing, concentration and crystallization. The isolated 2, 6-diethyl-4-methylphenylacetic acid may be purified by an additional treatment such as rectification and recrystallization .
[Example]
[0031]
Example 1
Under a nitrogen atmosphere, 2.46 g (88 mmol) of magnesium was added to the mixed solution of 80 g of THF, 0.11 g (0.4 mmol) of iodine and 0.88 g (4.4 mmol) of 1, 2-dibromoethane, and the obtained mixture was heated at 50 °C. Twenty (20) grams (88 mmol) of 2, 6-diethyl-4-methylbromobenzene dissolved in 20 g of THF was dropped thereto in small amounts from the drop funnel. After a while, a rise in inner temperature was confirmed, and then the remaining the solution of
2 , 6-diethyl-4-methylbromobenzene was dropped thereto slowly at the inner temperatures not in excess of 60 °C. After completion of the dropping, the mixture was stirred at 50 °C for 2 hours and then cooled to the room temperature. The obtained reaction mixture was dropped slowly to 100 g of 1.1 M THF solution of ethylene oxide which had kept cold at 0 °C. After completion of the dropping, the mixture was stirred at room temperature for 18 hours, and then, 100 mL of 1M aqueous solution of hydrochloric acid was added thereto to extract with 200 mL of ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled away. The obtained residue was purified with column chromatography (developing solvent: hexane/ethyl acetate) to obtain 8.1 g of 2- (2, 6-diethyl-4-methylphenyl) ethanol as a white crystal (yield 48 %) .
1H-NMR (CDC13) δ: 1.22 (6H, t, J = 7.7 Hz), 2.29. (3H, s), 2.66 (4H, q-, J = 7.7 Hz) , 2.95 (2H, t, J = 7.7 Hz) , 3.74 (2H, ' t, J = 7.7 Hz) , 6.88 (2H, s) . [0032]
Example 2
To the mixture of 1.75 g of water, 0.18 g of sodium hydrogen carbonate and 2.0 g of acetonitrile, 0.20 g (1.0 mmol) of 2- (2, 6-diethyl-4-methylphenyl) ethanol and 0.01 g (0.06 mmol) of TEMPO were added. The obtained mixture was cooled to 0 °C. Zero point zero one four (0.014) grams (0.02 mmol) of 11 % by weight aqueous solution of sodium hypochlorous acid was dropped thereto in 5 divided portions every 30 minutes. Continuously an aqueous solution wherein 0.24 g (2.1 mmol) of sodium chlorous acid had been dissolved in 0.94 g of water was dropped in 5 divided portions every 30 minutes. The reaction mixture after dropping was divided in 2 layers. Water (about 20 mL) was added until the reaction mixture became homogeneous solution. After that, the reaction mixture was extracted by 50 mL of chloroform, and the organic layer was dried with anhydrous magnesium sulfate, then the solvent was distilled away to obtain 0.18 g of 2, 6-diethyl-4-methylphenylacetic acid as a white crystal (yield 84 % ) .
XH-NMR (CDC13) δ: 1.19 (6H, t, J = 7.6 Hz), 2.30 (3H, s), 2.62 (4H, q, J = 7.6 Hz), 3.73 (2H,,s), 6.90 (2H, s).
[Industrial Applicability]
[0033]
According to the present invention,
2, 6-diethyl-4-methylphenylacetic acid .which is an important compound as a synthetic intermediate for a medicine and a pesticide and the like can be produced with shorter steps .

Claims

1. A method for producing 2, 6-diethyl-4-methylphenylacetic acid characterized by comprising a step of reacting a 2 , 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide to obtain 2- (2, 6-diethyl-4-methylphenyl) ethanol and a step of oxidizing 2- (2, 6-diethyl-4-methylphenyl ) ethanol.
2. The method according to claim 1, wherein the step of reacting a 2, 6-diethyl-4-methylphenyl magnesium halide with ethylene oxide is conducted in an ether solvent.
3. The method according to claim 1 or 2, wherein the step of oxidizing 2- (2 , 6-diethyl-4-methylphenyl ) ethanol is conducted in the presence of a nitroxyl radical compound.
4. The method according to any of claims 1-3, wherein the step of oxidizing 2- ( 2 , 6-diethyl- -methylphenyl ) ethanol is conducted in the presence of a salt of a hypohalous acid and/or a salt of a halous acid.
5. The method according to any of claims 1-3, wherein the step of oxidizing 2- (2, 6-diethyl-4-methylphenyl) ethanol is conducted in the presence of a salt of a hypohalous acid and a salt of a halous acid.
6. The method according to claim 4 or 5, wherein the salt of a hypohalous acid is a salt of hypochlorous acid.
7. The method according to claim 4 or 5, wherein the salt halous acid is a salt of chlorous acid. 2- (2, 6-diethyl-4-methylphenyl) ethanol
PCT/JP2012/080401 2011-12-02 2012-11-16 Method for producing 2,6-diethyl-4-methylphenylacetic acid WO2013080896A1 (en)

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WO2017121699A1 (en) 2016-01-15 2017-07-20 Bayer Cropscience Aktiengesellschaft Method for the preparation of substituted 2-aryl-ethanols
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