Classifications

• • 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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• Oil, Petroleum & Natural Gas (AREA)
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• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Citations (1)

• 2012
  • 2012-11-16 WO PCT/JP2012/080401 patent/WO2013080896A1/en active Application Filing
  • 2012-11-20 JP JP2012253936A patent/JP2013136561A/ja active Pending
  • 2012-11-29 AR ARP120104487 patent/AR089030A1/es not_active Application Discontinuation
  • 2012-11-30 TW TW101145134A patent/TW201326116A/zh unknown

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