WO2023054702A1 - アルデヒド化合物及びジヒドロイソキサゾール化合物の製造方法 - Google Patents

アルデヒド化合物及びジヒドロイソキサゾール化合物の製造方法 Download PDF

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WO2023054702A1
WO2023054702A1 PCT/JP2022/036818 JP2022036818W WO2023054702A1 WO 2023054702 A1 WO2023054702 A1 WO 2023054702A1 JP 2022036818 W JP2022036818 W JP 2022036818W WO 2023054702 A1 WO2023054702 A1 WO 2023054702A1
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mol
formula
compound
reaction
mmol
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PCT/JP2022/036818
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English (en)
French (fr)
Japanese (ja)
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開 瀧澤
崚 丸山
亮太 藤本
俊浩 永田
大介 志鎌
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クミアイ化学工業株式会社
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Priority to IL311693A priority Critical patent/IL311693A/en
Priority to CN202280038539.9A priority patent/CN117396464A/zh
Priority to JP2023551919A priority patent/JPWO2023054702A1/ja
Publication of WO2023054702A1 publication Critical patent/WO2023054702A1/ja

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/02—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen
    • C07C47/198—Saturated compounds having —CHO groups bound to acyclic carbon atoms or to hydrogen containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Definitions

  • the present invention is based on formula (7):
  • R 1 and R 2 are as described below.
  • compound ie, a method for producing dihydroisoxazole.
  • dihydroisoxazole is also referred to as isoxazoline.
  • the present invention provides formula (3) or formula (4):
  • the compound of formula (3) or formula (4) is useful as a production intermediate for pharmaceuticals, agricultural chemicals, and the like.
  • WO2002/062770A1 discloses useful herbicides and compounds of formula (3) or (4) can be used as intermediates for said herbicides.
  • Pyroxasulfone is well known as a herbicide having excellent herbicidal activity.
  • Patent Document 2 discloses a process for producing dihydroisoxazole, which can also be used as an intermediate for herbicides such as pyroxasulfone.
  • Patent Document 2 (WO2020/251006A1):
  • Patent Document 5 (WO2019/117255A1) also discloses a method for producing intermediates for herbicides such as pyroxasulfone.
  • Patent Document 5 (WO2019/117255A1):
  • Patent Document 6 (WO2019/208643A1) also discloses a method for producing intermediates for herbicides such as pyroxasulfone. The manufacturing method is shown in the figure below.
  • Patent Document 6 (WO2019/208643A1):
  • Patent Document 2 WO2020/251006A1
  • Patent Document 5 WO2019/117255A1
  • Patent Document 6 WO2019/208643A1
  • Patent Document 3 discloses an oxidation method using oxygen as a method for producing an aldehyde compound.
  • Patent Document 4 discloses an oxidation method using oxygen as a method for producing an aldehyde compound.
  • the alcohol compound of formula (1) was used as a starting material to react, but the aldehyde compound of formula (3) was The yield was low (Comparative Examples 10-12).
  • An object of the present invention is to provide an efficient and industrially preferable method for producing the compound of formula (7).
  • a further object of the present invention is to provide an industrially preferable method for producing the compound of formula (3) or (4).
  • a specific object is a method for producing a compound (aldehyde compound) of formula (3) or (4) from a compound (alcohol compound) of formula (1) or formula (2) by a simple operation, It is an object of the present invention to provide a production method in which the ratio of carboxylic acid derivatives and ester derivatives produced as organisms is sufficiently low, the yield is excellent, and it is advantageous for industrial production.
  • the present invention is as follows.
  • a method for producing a compound of formula (7) comprising the following steps; Step (i) reacting the compound of formula (1) or the compound of formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give the corresponding compound of formula (3) or formula ( 4) to obtain the compound:
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • Step (ii) reacting a compound of formula (3) or a compound of formula (4) with an oximating agent to give the corresponding compound of formula (5) or compound of formula (6) respectively:
  • Step (iii) reacting a compound of formula (5) or a compound of formula (6) in the presence of an acid catalyst or in the presence of an acid catalyst and a base catalyst to give a compound of formula (7):
  • a method for producing a compound of formula (7) comprising the following steps; Step (ia) reacting a compound of formula (1) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give a compound of formula (3):
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • Step (ii-a) reacting a compound of formula (3) with an oximating agent to give a compound of formula (5):
  • Step (iii-a) reacting a compound of formula (5) in the presence of an acid catalyst or in the presence of an acid catalyst and a base catalyst to give a compound of formula (7):
  • a method for producing a compound of formula (7) comprising the following steps; Step (ib) reacting a compound of formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give a compound of formula (4):
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • Step (ii-b) reacting a compound of formula (4) with an oximating agent to give a compound of formula (6):
  • Step (iii-b) reacting a compound of formula (6) in the presence of an acid catalyst or in the presence of an acid catalyst and a base catalyst to give a compound of formula (7):
  • a method for producing a compound of formula (3) or a compound of formula (4) comprising the following steps; Step (i) reacting the compound of formula (1) or the compound of formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give the corresponding compound of formula (3) or formula ( 4) to obtain the compound:
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • a method for producing a compound of formula (3) comprising the following steps; Step (ia) reacting a compound of formula (1) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give a compound of formula (3):
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • a method for producing a compound of formula (4) comprising the following steps; Step (ib) reacting a compound of formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give a compound of formula (4):
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • [I-8] The production method according to any one of [I-1] to [I-6], wherein the metal in step (i), step (ia) or step (ib) Processes of preparation wherein the catalyst is iron(III) nitrate or a catalyst comprising iron(III) chloride, iron(III) bromide or iron(III) iodide and nitric acid, except where not applicable.
  • step (i), step (ia) or step (ib) Processes where the catalyst is a catalyst comprising iron(III) chloride or iron(III) bromide and nitric acid, except where not applicable.
  • [I-12] The production method according to any one of [I-1] to [I-6], wherein the metal in step (i), step (ia) or step (ib) Processes of preparation wherein the catalyst is copper(II) nitrate, or a catalyst comprising copper(II) chloride, copper(II) bromide or copper(II) iodide and nitric acid, except where not applicable.
  • [I-13] The production method according to any one of [I-1] to [I-6], wherein the metal in step (i), step (ia) or step (ib) Processes where the catalyst is a catalyst comprising copper(II) chloride or copper(II) bromide and nitric acid, except where not applicable.
  • step (i), step (ia) or step (ib) is used in an amount of 0.01 mol to 0.1 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • step (i), step (ia) or step (ib) is used in an amount of 0.02 mol to 0.05 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • step (i), step (ia) or step (ib) is a carboxylic acid, except those not applicable.
  • step (i), step (ia) or step (ib) is acetic acid, propionic acid or benzoic acid, except those not applicable.
  • step (i), step (ia) or step (ib) is acetic acid, except those not applicable.
  • step (i), step (ia) or step (ib) is an aromatic heterocycle having a nitrogen atom, except those not applicable.
  • step (i), step (ia) or step (ib) is N-methylimidazole, 2,2'-bipyridyl, N-methylpyrazole, pyridine or N,N-dimethylaminopyridine, except those not applicable.
  • step (i), step (ia) or step (ib) is N-methylimidazole or 2,2'-bipyridyl, except those not applicable.
  • step (i), step (ia) or step (ib) The production method according to any one of [I-1] to [I-33], wherein the base in step (i), step (ia) or step (ib) is used in an amount of 0.01 to 0.1 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • [I-36] The production method according to any one of [I-1] to [I-35], wherein the metal in step (i), step (ia) or step (ib) A production method in which the amount of catalyst used is 0.001 to 0.3 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • [I-37] The production method according to any one of [I-1] to [I-35], wherein the metal in step (i), step (ia) or step (ib) A production method in which the amount of catalyst used is 0.01 to 0.1 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • step (i), step (ia) or step (ib) A production method in which the xyl radical compound is 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, except for those not applicable.
  • step (i), step (ia) or step (ib) A production method in which the amount of the xyl radical compound used is 0.001 to 0.3 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • step (i), step (ia) or step (ib) A production method in which the amount of the xyl radical compound used is 0.01 to 0.1 mol per 1 mol of the compound of formula (1) or the compound of formula (2), except for methods not applicable.
  • step (i), step (ia) or step (ib) is carried out in the presence of a solvent, wherein the solvent is aromatic hydrocarbons, ethers, ketones, nitriles and esters, preferably (C2-C4)alkanenitriles and (C1-C6)alkyl(C2-C4) ) Carboxylates), excluding those not applicable.
  • a solvent is aromatic hydrocarbons, ethers, ketones, nitriles and esters, preferably (C2-C4)alkanenitriles and (C1-C6)alkyl(C2-C4) ) Carboxylates
  • step (i), step (ia) or step (ib) is carried out in the presence of a solvent, wherein the solvent is one or more selected from nitriles and esters (preferably (C2-C4) alkanenitrile and (C1-C6) alkyl (C2-C4) carboxylate) ( (preferably 1 or 2, more preferably 1), except for those that are not applicable.
  • a solvent is one or more selected from nitriles and esters (preferably (C2-C4) alkanenitrile and (C1-C6) alkyl (C2-C4) carboxylate) (preferably 1 or 2, more preferably 1), except for those that are not applicable.
  • step (i), step (ia) or step (ib) is in the presence of a solvent, wherein the solvent is toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, tetrahydrofuran, dibutyl ether, acetone, methyl isobutyl ketone, acetonitrile, propionitrile, ethyl acetate, propyl acetate, isopropyl acetate , butyl acetate, and pentyl acetate (preferably 1 or 2, more preferably 1).
  • the solvent is toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, tetrahydrofuran, dibutyl ether, acetone, methyl isobutyl ketone, acetonitrile, propionitrile, ethyl acetate, propyl acetate, isoprop
  • step (i), step (ia) or step (ib) is carried out in the presence of a solvent, wherein the solvent is one or more (preferably one or two, more preferably one or two) selected from acetonitrile, propionitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and pentyl acetate 1), except for methods that are not applicable.
  • a solvent wherein the solvent is one or more (preferably one or two, more preferably one or two) selected from acetonitrile, propionitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and pentyl acetate 1), except for methods that are not applicable.
  • step (i), step (ia) or step (ib) is Processes of preparation carried out in the presence of a solvent, wherein said solvent is acetonitrile or butyl acetate, except for processes not applicable.
  • step (i), step (ia) or step (ib) is Processes of preparation carried out in the presence of a solvent, wherein said solvent is a (C1-C6)alkyl(C2-C4)carboxylate (preferably butyl acetate), except those processes not applicable.
  • a solvent wherein said solvent is a (C1-C6)alkyl(C2-C4)carboxylate (preferably butyl acetate), except those processes not applicable.
  • step (i), step (ia) or step (ib) is a continuous production method using a tubular flow reactor, excluding methods that are not applicable.
  • step (i), step (ia) or step (ib) is a production method that is carried out in a flow-through manner, except for methods that do not apply.
  • step (ii), step (ii-a) or step (ii-b) Processes where the agent is hydroxylamine, hydroxylamine salts or oxime compounds, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) Processes where the agent is an aqueous solution of hydroxylamine, hydroxylamine hydrochloride or hydroxylamine sulfate, except where not applicable.
  • step (ii), step (ii-a) or step (ii-b) Processes where the agent is 45% to 50% aqueous hydroxylamine solution, hydroxylamine hydrochloride or hydroxylamine sulfate, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) Processes in which the agent is hydroxylamine hydrochloride or hydroxylamine sulfate, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) Processes of manufacture in which the agent is hydroxylamine sulfate, except those not applicable.
  • R 4 and R 5 are each independently a hydrogen atom; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted optionally substituted (C2-C6) alkynyl; (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl .), except for methods that are not applicable.
  • step (ii), step (ii-a) or step (ii-b) A production method in which the amount of the agent used is 0.9 to 1.5 mol in terms of hydroxylamine (NH 2 OH) per 1 mol of the compound of formula (3) or the compound of formula (4), provided that , except for methods not applicable.
  • step (ii), step (ii-a) or step (ii-b) A production method in which the amount of the agent used is 1.0 to 1.3 mol in terms of hydroxylamine (NH 2 OH) per 1 mol of the compound of formula (3) or the compound of formula (4), provided that , except for methods not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Manufacturing processes carried out in the presence of a neutralizing agent, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) Processes in which the agent is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) A production method in which the amount of the agent used is 0.5 to 1.5 mol (preferably 0.9 to 1.5 mol) per 1 mol of the compound of formula (3) or the compound of formula (4), However, excluding methods that do not apply.
  • step (ii), step (ii-a) or step (ii-b) A production method in which the amount of the agent used is 1.0 to 1.3 mol per 1 mol of the compound of formula (3) or the compound of formula (4), except for methods not applicable.
  • step (ii), step (ii-a) or step (ii-b) is , aromatic hydrocarbons (preferably (C2-C4) alkanenitriles, (C1-C6) alkyl (C2-C4) carboxylates and (C1-C3) dichloroalkanes), ethers, ketones, nitriles, esters and halogenated aliphatic hydrocarbons, except those not applicable.
  • aromatic hydrocarbons preferably (C2-C4) alkanenitriles, (C1-C6) alkyl (C2-C4) carboxylates and (C1-C3) dichloroalkanes
  • ethers preferably (C2-C4) alkanenitriles, (C1-C6) alkyl (C2-C4) carboxylates and (C1-C3) dichloroalkanes
  • ketones ketones
  • nitriles esters
  • halogenated aliphatic hydrocarbons except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) is , nitriles, esters and halogenated aliphatic hydrocarbons (preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkane)
  • nitriles preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkane
  • Processes of manufacture carried out in the presence of one or more (preferably 1 or 2, more preferably 1) solvent, except for those processes which are not applicable.
  • step (ii), step (ii-a) or step (ii-b) The reaction is carried out in the presence of a solvent, and the solvent is an ester or halogenated aliphatic hydrocarbon (preferably (C1-C6) alkyl (C2-C4) carboxylate or (C1-C3) dichloroalkane) Manufacturing methods, except those not applicable.
  • a solvent is an ester or halogenated aliphatic hydrocarbon (preferably (C1-C6) alkyl (C2-C4) carboxylate or (C1-C3) dichloroalkane) Manufacturing methods, except those not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Processes carried out in the presence of a solvent, wherein the solvent is an ester (preferably (C1-C6)alkyl(C2-C4)carboxylate), except for processes not applicable.
  • a solvent wherein the solvent is an ester (preferably (C1-C6)alkyl(C2-C4)carboxylate), except for processes not applicable.
  • step (ii), step (ii-a) or step (ii-b) is , toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, tetrahydrofuran, dibutyl ether, acetone, methyl isobutyl ketone, acetonitrile, propionitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, pentyl acetate and dichloromethane.
  • a manufacturing method performed in the presence of one or more (preferably one or two, more preferably one).
  • step (ii), step (ii-a) or step (ii-b) is , acetonitrile, butyl acetate and dichloromethane (preferably 1 or 2, more preferably 1).
  • step (ii), step (ii-a) or step (ii-b) is Processes carried out in the presence of a solvent, where the solvent is butyl acetate or dichloromethane, except for processes not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Processes carried out in the presence of a solvent, where the solvent is butyl acetate, except for processes not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Manufacturing processes carried out at 0°C to 80°C, except for those not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Manufacturing processes carried out at 10°C to 50°C, except where not applicable.
  • step (iii), step (iii-a) or step (iii-b) is one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acid catalyst selected from the group consisting of mineral acids, carboxylic acids, and sulfonic acids, provided that , except for methods not applicable.
  • step (iii), step (iii-a) or step (iii-b) is nitric acid, trifluoroacetic acid, maleic acid or p-toluenesulfonic acid, except those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is nitric acid, excluding those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is trifluoroacetic acid, except for those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is maleic acid, except those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is used in an amount of 0.01 to 0.60 mol per 1 mol of the compound of formula (5) or the compound of formula (6), except for methods not applicable.
  • step (iii), step (iii-a) or step (iii-b) is used in an amount of 0.05 to 0.40 mol per 1 mol of the compound of formula (5) or the compound of formula (6), except for methods not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , a process carried out in the absence of a base catalyst.
  • step (iii), step (iii-a) or step (iii-b) is , a production process carried out in the presence of a basic catalyst.
  • step (iii), step (iii-a) or step (iii-b) is , a process carried out in the presence of an equivalent of a base catalyst that is less than the equivalent of the acid catalyst.
  • step (iii), step (iii-a) or step (iii-b) is , a production method carried out in the presence of a base catalyst of more than 0 (zero) equivalent and not more than 1 equivalent with respect to 1 equivalent of the acid catalyst.
  • step (iii), step (iii-a) or step (iii-b) is , a production method carried out in the presence of 0.1 to 0.5 equivalents of a base catalyst with respect to 1 equivalent of an acid catalyst.
  • step (iii), step (iii-a) or step (iii-b) is , a production method carried out in the presence of 0.2 to 0.4 equivalents of a base catalyst with respect to 1 equivalent of an acid catalyst.
  • step (iii), step (iii-a) or step (iii-b) is a secondary amine.
  • step (iii), step (iii-a) or step (iii-b) is N-methylaniline.
  • step (iii), step (iii-a) or step (iii-b) is used in an amount of 0.01 to 0.60 mol per 1 mol of the compound of formula (5) or the compound of formula (6).
  • step (iii), step (iii-a) or step (iii-b) is used in an amount of 0.05 to 0.40 mol per 1 mol of the compound of formula (5) or the compound of formula (6).
  • step (iii), step (iii-a) or step (iii-b) is , aromatic hydrocarbons, ethers, ketones, nitriles, esters and halogenated aliphatic hydrocarbons (preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkanes), except those not applicable.
  • aromatic hydrocarbons preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkanes
  • step (iii), step (iii-a) or step (iii-b) is , nitriles, esters and halogenated aliphatic hydrocarbons (preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkane)
  • nitriles preferably (C2-C4) alkanenitrile, (C1-C6) alkyl (C2-C4) carboxylate and (C1-C3) dichloroalkane
  • Processes of manufacture carried out in the presence of one or more (preferably 1 or 2, more preferably 1) solvent, except for those processes which are not applicable.
  • step (iii), step (iii-a) or step (iii-b) The reaction is carried out in the presence of a solvent, and the solvent is an ester or halogenated aliphatic hydrocarbon (preferably (C1-C6) alkyl (C2-C4) carboxylate or (C1-C3) dichloroalkane) Manufacturing methods, except those not applicable.
  • a solvent is an ester or halogenated aliphatic hydrocarbon (preferably (C1-C6) alkyl (C2-C4) carboxylate or (C1-C3) dichloroalkane) Manufacturing methods, except those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is Processes of preparation carried out in the presence of a solvent, wherein the solvent is an ester (preferably (C1-C6)alkyl(C2-C4)carboxylate), except for processes not applicable.
  • a solvent wherein the solvent is an ester (preferably (C1-C6)alkyl(C2-C4)carboxylate), except for processes not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, tetrahydrofuran, dibutyl ether, acetone, methyl isobutyl ketone, acetonitrile, propionitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, pentyl acetate and dichloromethane.
  • a manufacturing method performed in the presence of one or more (preferably one or two, more preferably one).
  • step (iii), step (iii-a) or step (iii-b) is , acetonitrile, butyl acetate and dichloromethane (preferably 1 or 2, more preferably 1).
  • step (iii), step (iii-a) or step (iii-b) is Processes carried out in the presence of a solvent, where the solvent is butyl acetate or dichloromethane, except for processes not applicable.
  • step (iii), step (iii-a) or step (iii-b) is Processes carried out in the presence of a solvent, where the solvent is butyl acetate, except for processes not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , manufacturing processes carried out in the presence of an aqueous solvent, except for those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , solvent-free manufacturing methods, except those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , -30°C to 160°C, except for those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , -10°C to 120°C, except for those not applicable.
  • step (iii), step (iii-a) or step (iii-b) is , manufacturing processes carried out at 0° C. to 100° C., except for those not applicable.
  • step (i) The method according to any one of [I-1] to [I-118], wherein the compound of formula (3) or the compound of formula (4) produced in step (i) is Processes of preparation in which the reaction of step (ii) is carried out without isolation, except where not applicable.
  • step (ii) The method according to any one of [I-1] to [I-118], wherein the compound of formula (5) or the compound of formula (6) produced in step (ii) is Processes of preparation in which the reaction of step (iii) is carried out without isolation, except for those processes that are not applicable.
  • step (i), step (ia) or step (ib) is Manufacturing processes carried out in the presence of an aqueous solvent, except those not applicable.
  • step (i), step (ia) or step (ib) is Manufacturing processes carried out in the presence of a solvent, where the solvent is water, except for those processes that are not applicable.
  • step (i), step (ia) or step (ib) is Manufacturing processes carried out in the presence of a solvent, the solvent containing water, except for those processes not applicable.
  • step (ii), step (ii-a) or step (ii-b) is Manufacturing processes carried out in the presence of a solvent, where the solvent is water, except for those processes that are not applicable.
  • step (i) The method according to any one of [I-1] to [I-136], wherein the reaction in step (ii), step (ii-a) or step (ii-b) is Manufacturing processes carried out in the presence of a solvent, the solvent containing water, except for those processes not applicable.
  • step (iii), step (iii-a) or step (iii-b) is Manufacturing processes carried out in the presence of a solvent, where the solvent is water, except for those processes that are not applicable.
  • step (iii), step (iii-a) or step (iii-b) is Manufacturing processes carried out in the presence of a solvent, the solvent containing water, except for those processes not applicable.
  • step (i), step (ia) or step (ib) is , production methods derived from oxygen generating agents (preferably nitric acid), excluding non-applicable methods.
  • a method for producing a compound of formula (7) comprising the following steps; Step (i) reacting the compound of formula (1) or the compound of formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound to give the corresponding compound of formula (3) or formula ( 4) to obtain the compound:
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl;
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • Step (ii) reacting a compound of formula (3) or a compound of formula (4) with an oximating agent to give the corresponding compound of formula (5) or compound of formula (6) respectively:
  • Step (iii) reacting a compound of formula (5) or a compound of formula (6) in the presence of an acid catalyst or in the presence of an acid catalyst and a base catalyst to give a compound of formula (7):
  • a method for producing a compound of formula (3) or a compound of formula (4) comprising: producing a compound of formula (1) or formula ( A process comprising reacting the compound of 2) to obtain the corresponding compound of formula (3) or compound of formula (4), respectively:
  • R 1 and R 2 are each independently optionally substituted (C1-C6) alkyl; R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl optionally substituted (C3-C6) cycloalkyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl(C1-C4) alkyl.
  • [II-7] The production method according to [II-6], wherein the metal catalyst is an iron catalyst or a copper catalyst.
  • [II-8] The production method according to [II-6], wherein the metal catalyst is iron (III) chloride.
  • the present invention provides a novel method for preparing compounds of formula (7). According to the present invention, an efficient and industrially preferable method for producing the compound of formula (7) is provided. Moreover, according to the present invention, the compound of formula (7) can be produced in a high yield by a simple operation. In addition, the present invention provides novel methods for preparing compounds of formula (3) or compounds of formula (4). According to the present invention, a more industrially preferable method for producing the compound of formula (3) or the compound of formula (4) is provided. Moreover, according to the present invention, by-products can be suppressed by a simple operation, and the compound of formula (3) or the compound of formula (4) can be produced in high yield.
  • the present invention can reduce the production of by-products and/or waste and improve atomic efficiency.
  • the present invention provides a method for producing a production intermediate for a herbicide such as pyroxasulfone easily and inexpensively on an industrial scale. Therefore, the method of the present invention is industrially preferable, economical, environmentally friendly, and has high industrial utility value.
  • FIG. 1 schematically shows the outline of the reactor of the present invention used in Example 11 in which the flow reaction was carried out.
  • BRIEF DESCRIPTION OF THE DRAWINGS It is a schematic diagram of an example of the reaction apparatus for enforcing the manufacturing method of this invention.
  • FIG. 2 schematically shows the outline of the reactor of the present invention used in Example 55 in which the flow reaction was carried out.
  • BRIEF DESCRIPTION OF THE DRAWINGS It is a schematic diagram of an example of the reaction apparatus for enforcing the manufacturing method of this invention.
  • FIG. 3 schematically shows the outline of the reactor of the present invention used in Example 56 in which the flow reaction was carried out.
  • BRIEF DESCRIPTION OF THE DRAWINGS It is a schematic diagram of an example of the reaction apparatus for enforcing the manufacturing method of this invention.
  • halogen atoms include fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.
  • (Ca-Cb) means that the number of carbon atoms is a to b.
  • “(C1-C4)" in “(C1-C4)alkyl” means that the alkyl has 1 to 4 carbon atoms.
  • alkyl are understood to include both straight and branched chains such as butyl and tert-butyl.
  • butyl when a specific term such as “butyl” is used, it is specific to "normal butyl” or “n-butyl”. In other words, the specific term “butyl” means straight chain “normal butyl”. and branched-chain isomers such as “tert-butyl” are specifically mentioned where intended.
  • n-, "s-” and “sec-”, “i-”, “t-” and “tert-”, [neo-], "c-” and “cyc-”, “o-” ”, “m-”, and “p-” have their usual meanings: normal, secondary (“s-” and “sec-”), iso, tertiary (“t-” and “ tert-”), neo, cyclo ("c-” and “cyc-”), ortho, meta, and para.
  • Me means methyl.
  • Et means ethyl.
  • Pr means propyl (ie normal propyl).
  • i-Pr and “Pr-i” mean isopropyl.
  • Bu means butyl (ie normal butyl).
  • s-Bu and “Bu-s” mean sec-butyl.
  • i-Bu and “Bu-i” mean isobutyl.
  • Pen pentyl (ie, normal pentyl).
  • Hex means hexyl (ie normal hexyl).
  • Dec means decyl (ie, normal decyl).
  • c-Pr and “Pr-c” mean cyclopropyl.
  • c-Bu and “Bu-c” mean cyclobutyl.
  • c-Pen and “Pen-c” mean cyclopentyl.
  • c-Hex and Hex-c mean cyclohexyl.
  • Ph means phenyl.
  • Bn means benzyl.
  • Ac means acetyl ( CH3CO- ).
  • (C1-C6) alkyl means a linear or branched alkyl having 1 to 6 carbon atoms.
  • Examples of (C1-C6)alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl and the like.
  • (C1-C4) alkyl means a linear or branched alkyl having 1 to 4 carbon atoms.
  • Examples of (C1-C4)alkyl are suitable examples of the above examples of (C1-C6)alkyl.
  • (C2-C4) alkanenitrile means (C1-C3) alkyl-CN.
  • Examples of (C2-C4)alkanenitriles are acetonitrile, propionitrile, butyronitrile, isobutyronitrile.
  • a C2 alkanenitrile is acetonitrile.
  • propionitrile is a C3 alkanenitrile.
  • Examples of (C1-C6)alkyl(C2-C4)carboxylates are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers, hexyl acetate and its isomers, Including, but not limited to, ethyl propionate, propyl propionate, isopropyl propionate, butyl propionate and isomers thereof.
  • butyl acetate is a (C4) alkyl (C2) carboxylate (ie, a C4 alkyl C2 carboxylate).
  • dichloroalkanes examples include, but are not limited to, dichloromethane, 1,2-dichloroethane, and the like.
  • dichloromethane is a C1 dichloroalkane.
  • aromatic hydrocarbon derivatives are those having 1 to 3 substituents (preferably 1 or 2) selected from the group consisting of (C1-C3)alkyl and chlorine atoms. It is benzene which may be substituted with a substituent, more preferred examples are toluene, xylene, chlorobenzene or dichlorobenzene, and further preferred examples are toluene or xylene. The foregoing may apply to all cases of the invention.
  • (C3-C6) cycloalkyl means cycloalkyl having 3 to 6 carbon atoms.
  • Examples of (C3-C6)cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
  • Examples of (C6-C10)aryl are phenyl, 1-naphthyl and 2-naphthyl.
  • (C6-C10)aryl(C1-C4)alkyl means (C1-C4alkyl) substituted by (C6-10)aryl, wherein the C6-10aryl moiety and the C1-C4alkyl moiety are have the same meaning as defined above.).
  • Examples of (C6-C10)aryl(C1-C4)alkyl are benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, naphthalen-1-ylmethyl, naphthalen-2-ylmethyl, etc. including but not limited to.
  • a cyclic hydrocarbon group means an aromatic or non-aromatic, monocyclic or polycyclic cyclic group in which all the atoms constituting the ring are carbon atoms.
  • examples of cyclic hydrocarbon groups are aromatic or non-aromatic, monocyclic, bicyclic or tricyclic 3- to 14-membered (preferably 5- to 14-membered, more preferably 5- to 10-membered) cyclic hydrocarbon groups.
  • examples of cyclic hydrocarbon groups are aromatic or non-aromatic, monocyclic or bicyclic (preferably monocyclic) 4-8 membered (preferably 5-6 membered) including, but not limited to, cyclic hydrocarbon groups of
  • cyclic hydrocarbon groups include, but are not limited to, cycloalkyl, aryl, and the like.
  • Aryl is an aromatic cyclic group among the cyclic hydrocarbon groups as defined above.
  • Cyclic hydrocarbon groups as defined or exemplified above may include non-fused cyclic (e.g. monocyclic or spirocyclic) and fused cyclic cyclic groups where possible. .
  • a cyclic hydrocarbon group as defined or exemplified above may be unsaturated, partially saturated or saturated, if possible.
  • a cyclic hydrocarbon group as defined or exemplified above is also referred to as a carbocyclic group.
  • a carbocyclic ring is a ring corresponding to a cyclic hydrocarbon group as defined or exemplified above.
  • substituted examples include one or more substituents (preferably 1 to 4 substituents), including but not limited to:
  • substituents independently selected from substituent group (a) are each independently selected from substituent group (b) may have one or more substituents (preferably 1 to 4 substituents).
  • substituent group (b) is the same as the substituent group (a).
  • a compound having isomers includes all isomers and any mixture thereof in any proportion.
  • xylene includes o-xylene, m-xylene, p-xylene and any mixture thereof in any proportion.
  • dichlorobenzene includes o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene and any mixture thereof in any proportion.
  • wavy lines in chemical formulas mean the following.
  • cis-trans isomers that is, E/Z isomers
  • E)-isomers anti-isomers
  • Z)-isomers mixtures thereof in any proportion are included in formulas with wavy underlines.
  • the method according to the present invention includes the following scheme (wherein R 1 , R 2 and R 3 are as described in [I-1] above).
  • Step (i) Step (i) will be explained. All descriptions of step (i) below apply to steps (ia) and (ib). Unless otherwise applicable.
  • step (i) is an oxidation reaction.
  • the reaction of step (i) is also called an oxidation step.
  • Step (i) is a manufacturing method comprising reacting the compound of formula (1) or formula (2) in the presence of a metal catalyst, nitric acid, oxygen and a nitroxyl radical compound.
  • the compound of formula (1) or the compound of formula (2) is used as a raw material.
  • the compound of formula (1) and the compound of formula (2) are known compounds, or can be produced from known compounds according to known methods.
  • Specific examples of compounds of formula (1) include, but are not limited to; 3-methyl-1,3-butanediol (3-methylbutane-1,3-diol or 3-hydroxy-3- methylbutanol), 3-methoxy-3-methylbutanol, 3-ethoxy-3-methylbutanol, 3-methyl-3-propoxybutanol, 3-isopropoxy-3-methylbutanol, 3-butoxy-3-methyl butanol, 3-isobutoxy-3-methylbutanol, 3-(sec-butoxy)-3-methylbutanol, 3-(benzyloxy)-3-methylbutanol and the like.
  • a preferred specific example of the compound of formula (1) is 3-methoxy-3-methylbutanol from the viewpoint of usefulness of the product.
  • a preferred specific example of the compound of formula (2) is 3-methyl-2-butenol (also referred to as prenol), but is not limited thereto.
  • oxygen in step (i) The oxidation reaction of the present invention is carried out in the presence of oxygen.
  • Oxygen may be used as an oxygen-containing gas (including, for example, pure oxygen and mixed gases such as air) and as an oxygen generating agent (e.g., nitric acid), and combinations thereof. may be used. Therefore, the method of the present invention includes at least one (preferably 1 to 3, more preferably one or two) and allowed to react.
  • oxygen-containing gas oxygen or air diluted with an inert gas (eg, nitrogen, carbon dioxide, argon, preferably nitrogen, carbon dioxide, more preferably nitrogen) can be used.
  • the oxygen concentration introduced may be any concentration as long as the reaction proceeds. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., it is preferably 1% by volume to 100% by volume, more preferably 5% by volume to 100% by volume.
  • the concentration of oxygen generated from an oxygen generating agent such as nitric acid may also be the same as described above.
  • nitroxyl radical compound in step (i) Conventionally known compounds can be used as nitroxyl radical compounds.
  • nitroxyl radical compounds include TEMPO-based catalysts (e.g., 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-hydroxy TEMPO or 4-OH-TEMPO), 4-methoxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-MeOTEMPO), 4-acetoxy-2,2,6,6-tetra methylpiperidine 1-oxyl (4-AcOTEMPO), 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl, 4-benzyloxy-2,2,6,6-tetramethylpiperidine 1-oxyl, 4-benzoyloxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-BzOTEMPO), etc.), AZADO catalysts (2-azaadamantane-N-oxyl
  • the compound of formula (1) or the compound of formula (2) (alcohol compound) is usually 0.0001 mol to 0.001 mol per 1 mol. 3 mol, preferably 0.001 mol to 0.1 mol.
  • metal catalyst in step (i) In one aspect, from the viewpoint of reactivity, yield, economic efficiency, etc., preferred examples of the metal catalyst for the oxidation reaction of the present invention include copper catalysts and iron catalysts. Specific examples of metal catalysts for the oxidation reaction of the present invention include copper catalysts (e.g., copper(II) nitrate, catalysts containing copper(II) chloride and nitric acid, catalysts containing copper(II) bromide and nitric acid, iodine copper(II) chloride and nitric acid), iron catalysts (e.g.
  • metal catalysts include copper catalysts and iron catalysts.
  • metal catalysts for the oxidation reaction of the present invention include copper catalysts (e.g., copper (II) nitrate, copper (II) chloride, copper (II) bromide, copper (II) iodide), iron catalysts ( For example, iron(III) nitrate, iron(III) chloride, iron(III) bromide), more preferably copper(II) nitrate, iron(III) chloride, iron(III) bromide, iron(III) nitrate More preferably iron(III) nitrate, iron(III) chloride, particularly preferably iron(III) chloride.
  • iron (III) chloride is cheaper than iron (III) nitrate, it is industrially and economically superior.
  • iron (III) chloride is less deliquescent than iron (III) nitrate and is easy to handle, it is easy to use industrially.
  • the metal catalyst may be in any form, and salts or hydrates thereof can also be used.
  • metal catalyst any amount of metal catalyst may be used as long as the reaction proceeds. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., it is preferably 0.0001 mol to 0.5 per 1 mol of the compound of formula (1) or the compound of formula (2) (alcohol compound). mol, more preferably 0.001 mol to 0.3 mol, still more preferably 0.01 mol to 0.1 mol.
  • nitric acid in step (i) The oxidation reaction of the present invention is carried out in the presence of nitric acid.
  • nitric acid is preferably used with copper(II) chloride, copper(II) bromide, copper(II) iodide, iron(III) chloride and iron(III) bromide.
  • nitric acid is used with a metal catalyst.
  • nitric acid it is preferable to use an aqueous nitric acid solution.
  • concentration of nitric acid in the nitric acid aqueous solution is not particularly limited, it is preferably 0.1 to 100%, more preferably 1 to 100%, still more preferably 10 to 90%, still more preferably 30 to 80%.
  • the nitric acid may be part of the catalyst (e.g., co-catalyst, promoter), an oxidant, an oxygen generator, a plurality of may be Any amount of nitric acid may be used as long as the reaction proceeds.
  • the catalyst e.g., co-catalyst, promoter
  • an oxidant e.g., oxygen generator
  • a plurality of may be Any amount of nitric acid may be used as long as the reaction proceeds.
  • it is generally 0.01 mol to 0.1 mol, preferably 0.02 mol to 0.09 mol, more preferably 0.02 mol to 0.05 mol. In still another embodiment, from the same viewpoint as above, it is usually 0.5 mol to 1 mol, preferably 0.5 mol to 0.9 mol, more preferably 0.5 mol to 0.8 mol.
  • an acid in the oxidation reaction of the present invention examples include carboxylic acids. Specific examples include preferably acetic acid, propionic acid, butanoic acid, isobutanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid and benzoic acid, more preferably acetic acid and propionic acid. , benzoic acid, more preferably acetic acid and propionic acid, still more preferably acetic acid, but not limited thereto.
  • the oxidation reaction of the present invention may or may not use an acid. When an acid is used, examples of acid are given above.
  • any amount of acid may be used as long as the reaction proceeds.
  • an acid is usually 0.1 per 1 mol of the compound of formula (1) or the compound of formula (2) (alcohol compound).
  • mol to 10 mol preferably 0.2 mol to 5 mol, more preferably 0.5 mol to 3 mol, still more preferably 1 mol to 2 mol.
  • bases include aromatic heterocyclic compounds having a nitrogen atom. Specific examples preferably include N-methylimidazole (NMI), N-methylpyrazole, pyridine, N,N-dimethylaminopyridine (DMAP), 2,2′-bipyridyl (BiPy), more preferably N -methylimidazole, 2,2'-bipyridyl, including but not limited to.
  • the oxidation reaction of the present invention may or may not use a base. When a base is used, examples of bases are as described above.
  • the form of the base may be any form as long as the reaction proceeds.
  • the base form can be appropriately selected by those skilled in the art.
  • any amount of base may be used as long as the reaction proceeds.
  • a base is usually 0.001 per 1 mol of the compound of formula (1) or the compound of formula (2) (alcohol compound). mol to 1 mol, preferably 0.001 mol to 0.3 mol, more preferably 0.01 mol to 0.1 mol.
  • the oxidation reaction of the present invention is preferably carried out in the presence of a solvent. Any solvent may be used for the oxidation reaction of the present invention as long as the reaction proceeds.
  • solvents examples include ethers (eg, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether), carboxylic acid esters (eg, (C1-C6)alkyl(C2- C4) carboxylates (e.g., methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers)), ketones (e.g., acetone, 2- butanone, methyl isobutyl ketone), aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene), nitriles (e.g., (C2-C4) alkanenitrile, (specifically, T
  • preferred examples of the solvent for the oxidation reaction of the present invention are carboxylic acid esters (preferably (C1-C6) alkyl (C2-C4) carboxylates), nitriles (preferably (C1-C6)alkyl(C2-C4)carboxylates) and any combination thereof in any proportion.
  • Preferred specific examples of solvents for the oxidation reaction of the present invention are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, acetonitrile, propionitrile and any combination thereof in any proportion. include.
  • More preferred specific examples are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, acetonitrile and any combination thereof in any proportion, more preferably butyl acetate and its isomers or acetonitrile, more preferably butyl acetate or acetonitrile.
  • preferred examples of solvents for the oxidation reaction of the present invention are carboxylic acid esters (preferably (C1-C6)alkyl(C2-C4)carboxylates).
  • More preferred specific examples are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof and any combination thereof in any proportion, more preferably butyl acetate and isomers thereof. and more preferably butyl acetate.
  • reaction of step (i) may be carried out in the presence of a water solvent.
  • a water solvent for example, water from an aqueous nitric acid solution (eg, 69% nitric acid) used as an oxygen generator can be understood as a water solvent.
  • any amount of the solvent may be used as long as the reaction system can be sufficiently stirred. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., 0 (zero) to 10 L (liter), preferably 0.1 to 1 mol of the compound of formula (1) or the compound of formula (2) Including but not limited to 5L, more preferably 0.3-2L.
  • the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.
  • the solvent may be a single layer or separated into two layers as long as the reaction proceeds.
  • step (i) is the compound of formula (3) or the compound of formula (4) corresponding to the compound of formula (1) or the compound of formula (2) used as starting material.
  • Specific examples, preferred specific examples, and more preferred specific examples thereof are as described below for the raw material of step (ii).
  • the compound of formula (3) or the compound of formula (4), which is the product of step (i), can be used as a starting material for step (ii).
  • the compound of formula (3) or the compound of formula (4) obtained in step (i) may be isolated and used in the next step, may be further purified and used in the next step, or may be isolated. It may be used in the next step without However, it is efficient to use it in the next step without isolation.
  • Step (ii) Step (ii) will be explained. All descriptions of step (ii) below apply to steps (ii-a) and (ii-b). Unless otherwise applicable.
  • step (ii) is oximation.
  • the reaction of step (ii) is also referred to as the oximation step.
  • Step (ii) is a step of reacting the compound of formula (3) or the compound of formula (4) with an oximating agent to produce the compound of formula (5) or the compound of formula (6).
  • step (ii); compound of formula (3) or compound of formula (4) A compound of formula (3) or a compound of formula (4) is used as a starting material for step (ii).
  • the compound of formula (3) or the compound of formula (4) is a known compound, or can be produced from a known compound according to a known method.
  • compounds of formula (3) or compounds of formula (4) include, but are not limited to; 3-methyl-2-butenal (also known as prenal), 3-hydroxy-3-methyl butanal (also known as 3-hydroxy-3-methyl-butan-1-al), 3-methoxy-3-methylbutanal, 3-ethoxy-3-methylbutanal, 3-methyl-3-propoxybutanal, 3-isopropoxy-3-methylbutanal, 3-butoxy-3-methylbutanal, 3-isobutoxy-3-methylbutanal, 3-(sec-butoxy)-3-methylbutanal, 3-methyl-3 -phenoxybutanal, 3-(benzyloxy)-3-methylbutanal, 3-hydroxy-3-methylpentanal, 3-ethyl-3-hydroxypentanal, 3-hydroxy-3,4-dimethylpentanal, 3-hydroxy-3,4,4-trimethylpentanal, 4-chloro-3-hydroxy-3-methylbutanal, 4,4,4-trifluoro-3-hydroxy-3-methylbutanal, 2-( 1-hydroxycyclopropyl
  • Preferred specific examples of the compound of formula (3) or the compound of formula (4) from the viewpoint of usefulness of the product are 3-hydroxy-3-methylbutanal and 3-methoxy-3-methylbutanal. is.
  • Preferred specific examples of the compound of formula (3) are as follows from the viewpoint of usefulness of the product, etc.; are), 3-methoxy-3-methylbutanal, 3-ethoxy-3-methylbutanal, 3-methyl-3-propoxybutanal, 3-isopropoxy-3-methylbutanal, 3-butoxy- 3-methylbutanal, 3-isobutoxy-3-methylbutanal, 3-(sec-butoxy)-3-methylbutanal, 3-(benzyloxy)-3-methylbutanal and the like.
  • a more preferred specific example of the compound of formula (3) from the same viewpoint as above is 3-methoxy-3-methylbutanal.
  • a preferred specific example of the compound of formula (4) is 3-methyl-2-butenal (also referred to as prenal).
  • the oximating agent used in step (ii) can be any oximating agent as long as the reaction proceeds.
  • oximating agents that can be used in step (ii) include hydroxylamine, hydroxylamine salts and oxime compounds.
  • the oximating agent is not particularly limited as long as the reaction proceeds and safety is ensured.
  • hydroxylamine (free) include, but are not limited to, 50% hydroxylamine aqueous solution, 60% hydroxylamine aqueous solution, 70% hydroxylamine aqueous solution, 80% hydroxylamine aqueous solution, 90% hydroxylamine aqueous solution, and the like.
  • hydroxylamine salts include, but are not limited to, hydroxylamine hydrochloride, hydroxylamine sulfate, hydroxylamine nitrate (e.g., 50% aqueous solution), hydroxylamine carbonate, hydroxylamine phosphate, hydroxylamine acetate, hydroxylamine oxalate, and the like. Not limited.
  • an oxime compound as an oximating agent is represented by the following formula.
  • the compound of formula (8) is a known compound, or can be produced from a known compound according to a known method.
  • Specific examples of compounds of formula (3) or compounds of formula (4) in which R 4 and R 5 do not form a ring include, but are not limited to; formoxime, acetone oxime (also known as acetoxime), 2-butanone oxime (methyl ethyl ketone oxime), methyl isopropyl ketone oxime, methyl tertiary butyl ketone oxime, 2-pentanone oxime, 3-pentanone oxime, 1-cyclohexyl-1- propanone oxime, 2-hexanone oxime, 3-hexanone oxime, 3-heptanone oxime, 4-octanone oxime, 5-nonanone oxime, acetoaldoxime, benzoaldoxime, acetophenone oxime, 4′-hydroxyacetophenone oxime, benzophen
  • compounds of formula (3) or compounds of formula (4) in which R 4 and R 5 form a non-conjugated ring include, but are not limited to; Cyclopropanone oxime, cyclobutanone oxime, cyclopentanone oxime, cyclohexanone oxime, cycloheptanone oxime, cyclooctanone oxime, cyclononanone oxime, cyclodecanone oxime and the like.
  • the oximating agent used in step (ii) may be used alone or in combination of two or more at any ratio.
  • the form of the oximating agent used in step (i) may be any form as long as the reaction proceeds and safety is ensured. As long as the reaction proceeds and safety is ensured, examples of its form include solids and liquids, aqueous solutions of any concentration, solutions of solvents other than water (eg, organic solvents), and the like.
  • the form of hydroxylamine may be in any form as long as the reaction proceeds and safety is ensured.
  • preferred examples of the hydroxylamine (free) form include aqueous solutions with a concentration of 10% or more and less than 70%, preferably 45% or more and 55% or less.
  • any amount of the oximating agent may be used in step (ii) as long as the reaction proceeds.
  • 1 mol of the compound of formula (3) or the compound of formula (4) is converted to hydroxylamine (NH 2 OH) , 0.9 to 1.5 equivalents, preferably 0.9 to 1.3 equivalents.
  • the amount used can be appropriately adjusted by those skilled in the art.
  • the meaning of the term "in terms of hydroxylamine ( NH2OH )" is as follows.
  • step (ii) is preferably carried out using a neutralizing agent.
  • Neutralizing agents are bases for neutralizing hydroxylamine salts to liberate free hydroxylamine.
  • neutralizing agents include alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (e.g., magnesium hydroxide, calcium hydroxide, water barium oxide, etc.), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkaline earth metal carbonates (e.g., magnesium carbonate, calcium carbonate, barium carbonate, etc.), alkali metal hydrogen carbonates (e.g., , lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), alkali metal carboxylates (e.g., lithium acetate, sodium acetate, potassium acetate, etc.), amines (e.g., triethylamine, tributylamine, diisopropylethylamine, 1,8 -diazabicyclo[5.4.0]-7-undec-7-ene (DBU), pyridine,
  • neutralizing agents include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc., ammonia, more preferably sodium hydroxide, sodium carbonate, sodium hydrogen carbonate, ammonia, More preferably it contains sodium hydroxide.
  • sodium hydroxide are sodium hydroxide beads, 48% aqueous sodium hydroxide solution, 25% aqueous sodium hydroxide solution, 10% aqueous sodium hydroxide solution, preferably 48% aqueous sodium hydroxide solution, 25% aqueous sodium hydroxide solution, and more It preferably contains, but is not limited to, 48% sodium hydroxide aqueous solution.
  • Neutralizing agents may be used alone or in combination of two or more in any proportion.
  • the form of the neutralizing agent may be any form as long as the reaction proceeds. Examples of its form include solids, liquids and gases of the neutralizing agent alone, as well as aqueous solutions of any concentration and solutions in solvents other than water (eg, organic solvents), and the like.
  • the form of the neutralizing agent can be appropriately selected by those skilled in the art.
  • the amount of the neutralizing agent used in step (ii) may be any amount as long as the reaction proceeds. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., 0.5 to 3.0 mol, preferably 0.5 to 1 mol, per 1 mol of the compound of formula (3) or the compound of formula (4) 0.5 mol, more preferably 0.8 to 1.5 mol, still more preferably 1.0 to 1.3 mol.
  • step (ii)) From the viewpoints of smooth progress of the reaction, safety, etc., the reaction of step (ii) is preferably carried out in the presence of a solvent. Any solvent may be used as long as the reaction in step (ii) proceeds and safety is ensured.
  • solvents examples include water, alcohols (e.g., methanol, ethanol, 2-propanol, butanol, tert-butanol (tert-butanol is also called tert-butyl alcohol), etc.), ethers (e.g., tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), nitriles (e.g., (C2-C4 ) alkanenitrile, (specifically, for example, acetonitrile, etc.)), carboxylic acid esters (for example, (C1-C6) alkyl (C2-C4) carboxylate, (specifically, for example, methyl acetate, acetic acid ethyl, prop
  • Preferred examples of the solvent in step (ii) from the viewpoint of reactivity, yield, safety, economic efficiency, etc. are water, alcohols, ethers, nitriles, carboxylic acid esters, aromatic hydrocarbon derivatives, Halogenated aliphatic hydrocarbons and any combination thereof in any proportion, more preferably water, nitriles, carboxylic acid esters, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and any proportion Any combination thereof, more preferably water, nitriles (preferably (C2-C4) alkanenitriles), carboxylic acid esters (preferably (C1-C6) alkyl (C2-C4) carboxylates), halogenated fats group hydrocarbons (preferably (C1-C3) dichloroalkanes) and any combination thereof in any proportion.
  • nitriles preferably (C2-C4) alkanenitriles
  • carboxylic acid esters preferably (C1-C6) alkyl (C2-C4) carboxylates
  • water is preferred in either case.
  • combinations of water and nitriles preferably (C2-C4)alkanenitrile
  • combinations of water and carboxylic acid esters preferably (C1-C6) alkyl (C2-C4) carboxylates
  • a combination of any proportion of water and halogenated aliphatic hydrocarbons preferably (C1-C3) dichloroalkane is preferred.
  • solvents in step (ii) are water, methanol, ethanol, 2-propanol, tert-butanol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, tetrahydrofuran (THF), toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any combination thereof in any proportion, more preferably water, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof , toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any combination thereof in any proportion, more preferably water, acetonitrile, methyl acetate, ethyl acetate, propy
  • the presence of water is preferred in either case.
  • combinations of water and acetonitrile in any proportion are preferred.
  • a combination of water and butyl acetate and its isomers in any proportion is preferred, and a combination of water and butyl acetate in any proportion is more preferred.
  • any combination of water and dichloromethane in any proportion is preferred.
  • the solvent may separate into a single layer or two layers as long as the reaction proceeds.
  • the water derived from the aqueous hydroxylamine solution can be understood as a solvent.
  • a neutralizing agent e.g., hydroxylamine hydrochloride, hydroxylamine sulfate, etc.
  • water from an aqueous solution of the neutralizing agent e.g., 48% aqueous sodium hydroxide solution
  • solvent e.g., 48% aqueous sodium hydroxide solution
  • Water produced by neutralization can also be understood as solvent.
  • the amount of solvent used in step (ii) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., 0 (zero) to 10 L (liter), preferably 0.02 to 1 mol of the compound of formula (3) or the compound of formula (4) 5 L, more preferably 0.02 to 1 L, still more preferably 0.1 to 1 L. However, the amount used can be appropriately adjusted by those skilled in the art.
  • the ratio of the two or more solvents may be any ratio as long as the reaction proceeds. The ratio can be adjusted appropriately by those skilled in the art.
  • the solvent may separate into a single layer or two layers as long as the reaction proceeds.
  • reaction temperature in step (ii) is not particularly limited. -30°C (minus 30°C) to 160°C, preferably -10°C to 80°C, more preferably 0°C to 80°C, still more preferably 10°C, from the viewpoint of yield, suppression of by-products, economic efficiency, etc. Up to 50°C, more preferably room temperature (10°C to 35°C) can be exemplified. However, the reaction temperature can be adjusted appropriately by those skilled in the art.
  • reaction time of step (ii) The reaction time of step (ii) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., the time is 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, more preferably 0.5 hours to 12 hours. However, the reaction time can be adjusted appropriately by those skilled in the art.
  • the product of step (ii) is the compound of formula (5) or the compound of formula (6) corresponding to the compound of formula (3) or the compound of formula (4) used as starting material.
  • Specific examples include, but are not limited to; 3-methyl-2-butenal oxime, 3-hydroxy-3-methylbutanal oxime (3-hydroxy-3-methyl-butane-1- oxime), 3-methoxy-3-methylbutanal oxime, 3-ethoxy-3-methylbutanal oxime, 3-methyl-3-propoxybutanal oxime, 3-isopropoxy-3-methylbutanal oxime , 3-butoxy-3-methylbutanal oxime, 3-isobutoxy-3-methylbutanal oxime, 3-(sec-butoxy)-3-methylbutanal oxime, 3-methyl-3-phenoxybutanal oxime, 3 -(benzyloxy)-3-methylbutanal oxime, 3-hydroxy-3-methyl-pentanal
  • Preferred specific examples of the compound of formula (5) are 3-hydroxy-3-methylbutanal oxime and 3-methoxy-3-methylbutanal oxime, more preferably 3 -Methoxy-3-methylbutanal oxime.
  • a preferred specific example of formula (6) is 3-methyl-2-butenaloxime.
  • step (ii) The compound of formula (5) or the compound of formula (6), which is the product of step (ii), can be used as a starting material for step (iii).
  • the compound of formula (5) or the compound of formula (6) obtained in step (ii) may be isolated and used in the next step, may be further purified and used in the next step, or may be isolated It may be used in the next step without However, it is efficient to use it in the next step without isolation.
  • Step (iii) Step (iii) will be explained. All descriptions of step (iii) below apply to steps (iii-a) and (iii-b). Unless otherwise applicable.
  • step (iii) is a cyclization reaction.
  • Step (iii) is also referred to as a cyclization step.
  • Step (iii) is a step of reacting the compound of formula (5) or the compound of formula (6) in the presence of a catalyst to produce the compound of formula (7).
  • step (iii); compound of formula (5) or compound of formula (6) The compound of formula (5) or the compound of formula (6) is used as the starting material for step (iii).
  • the compound of formula (5) or the compound of formula (6) is a known compound, or can be produced from a known compound according to a known method.
  • compounds of formula (5) or compounds of formula (6) can be prepared by the method of step (ii) above. Specific examples and preferred specific examples of the compound of formula (5) or the compound of formula (6) are as described above.
  • the catalyst in step (iii) can be any catalyst as long as the reaction proceeds.
  • an acid catalyst can be used, or an acid catalyst and a base catalyst can be used.
  • (Acid catalyst in step (iii)) In one aspect of the invention, compounds of formula (7) are prepared in the presence of an acid catalyst.
  • the acid catalyst may be any acid catalyst as long as the reaction proceeds. Additionally, as long as the reaction proceeds, any of the following forms may be used and are within the scope of the present invention. Free acids can be used as acid catalysts.
  • Acid catalysts may be used in the form of salts. When the acid catalyst is a salt, the acid catalyst may be a single salt or a double salt.
  • the acid catalyst may be used in the anhydride form.
  • Acid catalysts may be used in the form of hydrates.
  • the acid catalyst may be used in the form of dimers and the like.
  • acid catalysts in step (iii) include, but are not limited to:
  • Mineral acids can be used as acid catalysts in step (iii).
  • mineral acids include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid.
  • Carboxylic acids, their salts and anhydrides can be used as acid catalysts in step (iii). Accordingly, the carboxylic acid may be used as the free acid or as its salt. Additionally, the carboxylic acid may be used as its anhydride. Specific examples of carboxylic acids include acetic acid, trifluoroacetic acid (TFA), trichloroacetic acid, dichloroacetic acid, maleic acid, citric acid, benzoic acid, phthalic acid. Specific examples of preferred carboxylic acids include trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, maleic acid.
  • TFA trifluoroacetic acid
  • trichloroacetic acid dichloroacetic acid
  • maleic acid citric acid
  • benzoic acid phthalic acid
  • preferred carboxylic acids include trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, maleic acid.
  • carboxylates are ammonium trifluoroacetate (CF 3 COO - NH 4 + )), N-methylanilium trifluoroacetate (CF 3 COO - C 6 H 5 N + (CH 3 )H 2 )including.
  • carboxylic anhydrides include trifluoroacetic anhydride, maleic anhydride, phthalic anhydride.
  • a specific example of a preferred carboxylic anhydride includes maleic anhydride.
  • Sulfonic acids can be used as acid catalysts in step (iii). Accordingly, the sulfonic acid may be used as the free acid or as its salt. Additionally, the sulfonic acid may be used as its anhydride.
  • sulfonic acids include methanesulfonic acid, trifluoromethanesulfonic acid (TfOH), benzenesulfonic acid, p-toluenesulfonic acid (including p-toluenesulfonic acid monohydrate (TsOH.H 2 O)), 10- Contains camphorsulfonic acid.
  • sulfonates include pyridinium p-toluenesulfonate (PPTS).
  • PPTS pyridinium p-toluenesulfonate
  • sulfonic anhydrides include methanesulfonic anhydride, trifluoromethanesulfonic anhydride.
  • preferred examples of the acid catalyst are as follows, but are not limited thereto.
  • One or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acids selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids and phosphoric acids are preferred.
  • Amines are preferable as the basic catalyst.
  • R 6 , R 7 and R 8 are each independently a hydrogen atom, optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted optionally substituted (C2-C6)alkenyl; optionally substituted (C2-C6)alkynyl; or optionally substituted aryl; or any two of R 6 , R 7 and R 8 are taken together with the nitrogen atom to which they are attached form a 4- to 12-membered heterocyclic ring wherein the ring formed is optionally substituted wherein R 6 , R 7 and R 8 is not a hydrogen atom) primary amines, secondary amines, tertiary amines, or heterocyclic amines.
  • primary amines include, but are not limited to, methylamine, ethylamine, propylamine, butylamine, aniline, and the like.
  • secondary amines include diethylamine, dipropylamine, diisopropylamine, N-methylaniline (PhNHMe; herein sometimes abbreviated as N-MeAniline), N-ethylaniline, piperidine, Including, but not limited to, morpholine and the like.
  • tertiary amines are triethylamine, tripropylamine, tributylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO), N,N-dimethylaniline, N,N - including but not limited to diethylaniline and the like;
  • heterocyclic amines are pyridine, 4-(dimethylamino)-pyridine, 4-pyrrolidinopyridine, 2,6-lutidine, quinoline, isoquinoline, 1,8-diazabicyclo[5.4.0] -7-undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), and the like.
  • Examples of amines also include imidazolinones.
  • Specific examples of imidazolinones include optical isomers such as (2S,5S)-2-tert-butyl-3-methyl-5-benzyl-4-imidazolinone and diastereomers thereof, and analogs thereof including.
  • imidazolinones are expensive, it is industrially preferable not to use imidazolinones.
  • preferred examples of the base of the acid-base catalyst include secondary amines or heterocyclic amines.
  • Preferred specific examples of acid-base catalyst bases include N-methylaniline or pyridine.
  • the amount of the acid catalyst used is 0.01 to 1.0 mol per 1 mol of the compound of formula (5) or the compound of formula (6), from the viewpoint of yield, suppression of by-products, economic efficiency, etc. , preferably 0.01 to 0.60 mol, more preferably 0.02 to 0.50 mol, and 0.05 to 0.40 mol.
  • the amount of the basic catalyst used is 0 (zero) to 1.0 per 1 mol of the compound of formula (5) or the compound of formula (6) from the viewpoint of yield, suppression of by-products, economic efficiency, etc. Molar ranges can be exemplified.
  • the amount of the basic catalyst used is 0.01 to 1.0 mol, preferably 0.01 to 0.60 mol, more preferably 0.02 to 0.50 mol, and 0.05 to 0.05 mol. A range of 0.40 mol can be exemplified.
  • the ratio of the base catalyst to the acid-base catalyst may be 1:1, or may not be 1:1.
  • step (iii)) The reaction of step (iii) can be carried out in the presence or absence of a solvent (no solvent).
  • a solvent used in the reaction of step (iii)
  • any solvent may be used as long as the reaction of step (iii) proceeds.
  • solvents when using solvents include water, alcohols (e.g., methanol, ethanol, 2-propanol, butanol, tert-butanol (tert-butanol is also called tert-butyl alcohol), etc.), ethers ( For example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), nitriles (e.g., (C2-C4) alkanenitrile, (specifically, for example, acetonitrile, etc.)), carboxylic acid esters (e.g., (C1-C6) alkyl (C2-C4) carboxylate, specifically, (e.g., methyl acetate, ethyl acetate
  • Preferred examples of the solvent in step (ii) from the viewpoint of reactivity, yield, safety, economic efficiency, etc. are water, alcohols, ethers, nitriles, carboxylic acid esters, aromatic hydrocarbon derivatives, Halogenated aliphatic hydrocarbons and any combination thereof in any proportion, more preferably water, nitriles, carboxylic acid esters, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and any proportion Any combination thereof, more preferably water, nitriles (preferably (C2-C4) alkanenitriles), carboxylic acid esters (preferably (C1-C6) alkyl (C2-C4) carboxylates), halogenated fats group hydrocarbons (preferably (C1-C3) dichloroalkanes) and any combination thereof in any proportion.
  • nitriles preferably (C2-C4) alkanenitriles
  • carboxylic acid esters preferably (C1-C6) alkyl (C2-C4) carboxylates
  • Water may or may not be present.
  • combinations of water and nitriles preferably (C2-C4)alkanenitrile
  • combinations of water and carboxylic acid esters preferably (C1-C6) alkyl (C2-C4) carboxylates
  • a combination of any proportion of water and halogenated aliphatic hydrocarbons preferably (C1-C3) dichloroalkane is preferred.
  • solvents in step (iii) are water, methanol, ethanol, 2-propanol, tert-butanol, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, tetrahydrofuran (THF), toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any combination thereof in any proportion, more preferably water, acetonitrile, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isomers thereof , toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any combination thereof in any proportion, more preferably water, acetonitrile, methyl acetate, ethyl acetate, prop
  • Water may or may not be present. .
  • a combination of water and acetonitrile in any proportion, or acetonitrile is preferred.
  • a combination of water and butyl acetate and its isomers in any proportion, or butyl acetate and its isomers is preferred, and a combination of water and butyl acetate in any proportion or butyl acetate is more preferred.
  • a combination of water and dichloromethane in any proportion, or dichloromethane is preferred. In either case, the solvent may separate into a single layer or two layers as long as the reaction proceeds.
  • any amount may be used as long as the reaction system can be sufficiently stirred. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., 0 (zero) to 10 L (liter), preferably 0.1 to 1 mol of the compound of formula (5) or the compound of formula (6) 5L.
  • the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.
  • the solvent may be a single layer or separated into two layers as long as the reaction proceeds.
  • step (ii) and step (iii) are performed without isolating the compound of formula (5) or the compound of formula (6)
  • the amount of solvent and the like in step (iii) is Alternatively, it can be set by the ratio with the compound of formula (4).
  • the amount of solvent used in step (iii) is 0 (zero) to 10 L (liter), preferably 0.1 to 5 L, per 1 mol of the compound of formula (3) or the compound of formula (4). is.
  • reaction temperature of step (iii) The reaction temperature of step (iii) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., the temperature is -30°C (minus 30°C) to 160°C, preferably -10°C to 120°C, more preferably 0 to 100°C.
  • reaction time of step (iii) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., the time is 0.5 hours to 72 hours, preferably 1 hour to 60 hours, more preferably 1 hour to 48 hours.
  • the product of step (iii) is the compound of formula (7) corresponding to the compound of formula (5) or the compound of formula (6) used as starting material.
  • Specific examples include, but are not limited to; 5,5-dimethyl-4,5-dihydroisoxazole, 5-ethyl-5-methyl-4,5-dihydroisoxazole, 5, 5-diethyl-4,5-dihydroisoxazole, 5-isopropyl-5-methyl-4,5-dihydroisoxazole, 5-(tert-butyl)-5-methyl-4,5-dihydroisoxazole , 5-(chloromethyl)-5-methyl-4,5-dihydroisoxazole, 5-methyl-5-(trifluoromethyl)-4,5-dihydroisoxazole, 5-cyclopropyl-5-methyl -4,5-dihydroisoxazole, 5-cyclobutyl-5-methyl-4,5-dihydroxazole,
  • reaction embodiment The following descriptions of "reaction embodiments" apply to steps (i), steps (ia), and steps (ib). Unless otherwise applicable.
  • This reaction can be carried out in a batch system (batch system) using a reactor, or can be carried out in a flow reaction using a continuous reactor.
  • a continuous reactor is a reactor for supplying raw materials and allowing reactions to proceed continuously at the same time.
  • As a continuous reactor there is a flow reactor.
  • a flow reactor is a reactor in which raw materials can be continuously fed and reacted continuously.
  • Flow reactors are broadly classified into tubular flow reactors (including tubular flow reactors) and tank flow reactors, both of which can carry out reactions in a continuous manner.
  • the flow reactor of the present invention may be provided with temperature control means for controlling the temperature of the flow reactor, for example, may be provided with a temperature control unit for heating and cooling.
  • the temperature control section may be of any suitable type, examples of temperature control sections include baths and jackets.
  • the style of the bath and jacket may be of any suitable style.
  • the material of the flow reactor is not particularly limited as long as it is not attacked by the raw material and solvent. Examples include glass, porcelain (eg, ceramics), and the like.
  • the continuous reaction of the present invention does not exclude implementation in a tank-type flow reactor.
  • preferred flow reactors include, for example, tubular flow reactors.
  • the tubular flow reactor of the present invention may be any one capable of continuously circulating a liquid or gas-liquid mixture. , or a combination of these shapes.
  • the material of the tube is not particularly limited as long as it is resistant to raw materials and solvents. (for example, ceramics), etc., but metals with excellent pressure resistance are preferable.
  • the tubular flow reactor of the present invention may also be provided with temperature control means for controlling the temperature, for example, a temperature control section for heating and cooling may be provided.
  • the temperature control section may be of any suitable type, and examples of temperature control sections include baths, jackets, and the like.
  • the style of the bath and jacket may be of any suitable style.
  • a spiral reactor, shell-and-tube reactor, plate heat exchange reactor, or the like can be used.
  • tubes in the tubular flow reactor of the present invention may be straight, curved, or coiled.
  • a preferred arrangement method includes, for example, a tubular reactor in which tubes are arranged in a coil.
  • the number of tubes may be one, but two or more tubes may be bundled regularly or irregularly at appropriate intervals.
  • the present specification will be described based on a tubular flow reactor having a single tube. can also be used in a tubular flow reactor in which the are bundled regularly or irregularly at appropriate intervals.
  • the tubular flow reactor of the present invention may have a mixer, if necessary.
  • the mixer is not particularly limited as long as it has a function of continuously mixing two or more fluids such as gas and liquid or liquid and liquid.
  • Examples include Y-shaped mixer, T-shaped mixer, pipe Line type mixers (line mixers including static mixers, etc.) and the like can be mentioned.
  • Line mixers, including static mixers and the like, may be tubular flow reactors.
  • metal catalyst, nitroxyl radical, nitric acid, alcohol compound (1) or alcohol compound (2) and a predetermined amount of solvent are added to the reactor (add more if necessary). good), and the reaction mixture is stirred at a given temperature for a given time in the presence of oxygen.
  • the reaction temperature is not particularly limited.
  • Reaction time is not particularly limited.
  • the time is 0.1 hour to 48 hours, preferably 0.1 hour to 24 hours, more preferably 1 hour to 12 hours.
  • flow-through reaction The following description of "flow-through reaction” applies to step (i), step (ia) and step (ib). In addition, it may apply to all steps except where not applicable.
  • a metal catalyst, nitroxyl radical, alcohol compound (1) or alcohol compound (2), and a predetermined amount of a mixture of a solvent (additional amounts may be added if necessary) are placed in a tubular reactor. is circulated, and oxygen is circulated and reacted from another tube.
  • a tubular reactor equipped with a heating device it is preferable to use a tubular reactor equipped with a heating device, and to pass the mixture through the reaction tube heated to a predetermined temperature.
  • the reaction temperature is not particularly limited. However, from the viewpoint of yield, suppression of by-products, economic efficiency, etc., it is 0°C (zero) to 120°C, preferably 40°C to 100°C.
  • the equivalent diameter of the tube in the tubular reactor of the present invention is not particularly limited as long as it is a size that allows the liquid or gas-liquid mixture to flow continuously. It is preferable that the thickness is 0.5 mm or more from the point of view of production efficiency and reaction may occur. Examples of preferable equivalent diameters include 0.5 mm to 50 mm, preferably 0.5 mm to 30 mm.
  • the length of the tube of the tubular flow reactor of the present invention is not particularly limited as long as the temperature of the raw material compound can be raised and sufficient reaction can occur.
  • it is 1 m or more, preferably 1 m to 100 m, more preferably 5 m to 80 m.
  • it is necessary to react at a predetermined temperature and/or for a sufficient reaction time. Not limited.
  • the flow velocity in the flow reactor of the present invention depends on the equivalent diameter of the tube, but for example, the lower limit is usually 0.1 m/min or more, preferably 1.0 m/min or more. is. In addition, for example, the upper limit is usually 4.0 m/min or less, preferably 3.0 m/min or less.
  • the pressure in the tubular flow reactor is, for example, 0.1 MPa to 10 MPa, preferably 0.1 MPa to 5 MPa, more preferably 0.1 MPa to 1 MPa, but is not limited thereto.
  • the same organic solvents are preferably carboxylic acid esters, more preferably (C1-C6) alkyl (C2-C4) carboxylates.
  • Said same organic solvent is more preferably selected from the group consisting of methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and its isomers, pentyl acetate and its isomers.
  • the same organic solvent mentioned above is more preferably butyl acetate and its isomers, particularly preferably butyl acetate.
  • room temperature is from 10°C to 35°C.
  • Acetonitrile (7.9 g, 1.0 L/mol), iron (III) bromide (89 mg, 0.30 mmol, 3.0 mol%), 69% nitric acid (27 mg, 0.0 mol%) were placed in a 50 mL eggplant-shaped flask.
  • Acetonitrile (7.9 g, 1.0 L / mol), iron (III) chloride (49 mg, 0.30 mmol, 3.0 mol%), 69% nitric acid (27 mg, 0.30 mmol, 3.0 mol%), propionic acid (741 mg, 10.0 mmol, 100 mol%), N-methylimidazole (25 mg, 0.30 mmol, 3.0 mol%), 4-hydroxy-2 , 2,6,6-tetramethylpiperidine 1-oxyl (69 mg, 0.40 mmol, 4.0 mol%), 3-methoxy-3-methylbutanol (1.18 g, 10.0 mmol, 100 mol %) was added, and the mixture was stirred at 60° C.
  • reaction tube part inner diameter 1 mm, length 40 m
  • the reaction tube was heated to 80 ° C., and then at 0.6 MPa, the raw material solution was supplied at a flow rate of 1 mL / min, and oxygen gas was supplied. It was supplied to the reaction tube at 30 mL/min.
  • a reaction mixture was sampled from the outlet of a pressure regulating valve attached to the outlet of the reaction tube, and GC analysis (area percentage) of the reaction mixture was performed. The results of the analysis were as follows; 3-Methoxy-3-methylbutanal (target product (3-a)): 93%, 3-Methoxy-3-methylbutanoic acid (side product (9-a)): N.D. .
  • the apparatus used is shown in FIG.
  • Butyl acetate (112.9 mL, 0.75 L/mol), iron (III) chloride (490 mg, 3.0 mmol, 2.0 mol%), 4-hydroxy-2,2 were placed in a 200 mL four-necked flask. , 6,6-tetramethylpiperidine 1-oxyl (1.03 g, 6.0 mmol, 4.0 mol%), 3-methyl-2-butenol (12.92 g, 150 mmol, 100 mol%) Then, while stirring at 60° C., 69% nitric acid (6.85 g, 75 mmol, 50 mol %) was added dropwise over 5 hours, and 5 vol % oxygen-containing nitrogen was added at 20 mL/min.
  • Example 17 The reaction and analysis were carried out in the same manner as in Example 17, except that the solvent and reaction time were changed as shown in Table 1. Table 1 shows the results. In addition, the results of Example 17 are also summarized in Table 1.
  • Butyl acetate (112.9 mL, 0.75 L/mol), iron (III) chloride (490 mg, 3.0 mmol, 2.0 mol%), 4-hydroxy-2,2 were placed in a 200 mL four-necked flask. , 6,6-tetramethylpiperidine 1-oxyl (1.03 g, 6.0 mmol, 4.0 mol%), 3-methyl-2-butenol (12.92 g, 150 mmol, 100 mol%) In addition, 69% nitric acid (8.22 g, 90 mmol, 60 mol %) was added dropwise over 6 hours while stirring at 60°C, and the mixture was reacted at the same temperature for 2 hours. GC analysis (area percentage) of the reaction mixture was performed. The results of the analysis were as follows; 3-methyl-2-butenal (target product (4-a)): 94%, 3-methyl-2-butenoic acid (side product (10-a)): N.D. .
  • Example 24 The reaction and analysis were carried out in the same manner as in Example 24, except that the amount of iron chloride used, the amount of 4-hydroxy TEMPO used (equiv.), the amount of solvent, and the reaction temperature were changed as shown in Table 2. rice field. Table 2 shows the results. In addition, the results of Example 24 are also summarized in Table 2.
  • an aqueous sodium hydroxide solution 25 wt %, 16 g, 100 mmol, 100 mol %) was added dropwise with stirring over 30 minutes, followed by a 2 M aqueous hydroxylamine sulfate solution (34.85 g, hydroxylamine ( 104 mmol as hydroxylamine (NH 2 OH) and 104 mol % as hydroxylamine (NH 2 OH)) were added dropwise over 30 minutes.
  • the resulting mixture was filtered and partitioned into an organic layer and an aqueous layer, and the organic layer and aqueous layer were separated at 20-25°C.
  • the reaction formula is the same as in Example 31.
  • Butyl acetate (75.0 mL, 0.50 L/mol), iron (III) chloride (243 mg, 1.5 mmol, 1.0 mol%), 4-hydroxy-2,2 were placed in a 200 mL four-necked flask. , 6,6-tetramethylpiperidine 1-oxyl (1.03 g, 6.0 mmol, 4.0 mol%), 3-methyl-2-butenol (12.92 g, 150 mmol, 100 mol%) In addition, 69% nitric acid (8.90 g, 97.5 mmol, 65 mol %) was added dropwise over 6.5 hours while stirring at 60°C, and the mixture was reacted at the same temperature for 0.5 hours. GC analysis (area percentage) of the reaction mixture was performed.
  • 3-Methyl-2-butenal (15.0 g, 178 mmol, 100 mol %) was dissolved in dichloromethane (90 ml, 0.5 L/mol).
  • a 50% hydroxylamine aqueous solution (11.8 g, 178 mmol, 100 mol %) was added dropwise thereto so that the internal temperature was 30 to 40° C. (exothermic reaction). After the dropwise addition was completed, the mixture was stirred at room temperature for 4 hours. After completion of the reaction, saline (10 ml) was added and stirred. The resulting mixture was partitioned into organic and aqueous layers. The organic layer and aqueous layer were separated to obtain an organic layer.
  • Trifluoroacetic acid (TFA, 2.03 g, specific gravity: 1.49, 1.36 ml, 17.8 mmol, 10 mol%) was added thereto and stirred at room temperature for 48 hours.
  • the main components excluding the solvent etc. in the reaction mixture were as follows; 5,5-dimethyl-4,5-dihydroisoxazole (target product (7-a)): 94%, 3-methyl-2-butenal oxime (intermediate (6-a)): 1%.
  • Diethyl ether (40 ml) was added to the reaction mixture and the resulting mixture was partitioned between organic and aqueous layers. The organic layer and aqueous layer were separated to obtain an organic layer.
  • the reaction formula is the same as in Example 33.
  • 3-Methyl-2-butenal (10.0 g, 119 mmol, 100 mol %) was dissolved in dichloromethane (60 ml, 0.5 L/mol).
  • a 50% hydroxylamine aqueous solution (7.9 g, 119 mmol, 100 mol %) was added dropwise thereto so that the internal temperature was 30 to 40° C. (exothermic reaction).
  • the mixture was stirred at room temperature for 4 hours.
  • saline (10 ml) was added and stirred.
  • the resulting mixture was partitioned into organic and aqueous layers. The organic layer and aqueous layer were separated to obtain an organic layer.
  • the reaction formula is the same as in Example 33.
  • the aqueous layer was extracted with a small amount of dichloromethane. At this time, the pH of the aqueous layer was 6.6.
  • the organic layers obtained above were combined in a 50 ml round-bottomed flask (the amount of dichloromethane used was 23 ml in total, 0.2 L/mol in total).
  • Maleic acid (1.35 g, 11.7 mmol, 10 mol %) was added thereto and stirred at 30° C. for 48 hours.
  • the components other than the solvent etc. in the reaction mixture were as follows; 5,5-dimethyl-4,5-dihydroisoxazole (target product (7-a )): 96%.
  • the reaction formula is the same as in Example 33.
  • Hydroxylamine sulfate (10.5 g, 128 mmol as hydroxylamine (NH 2 OH), 110 mol% as hydroxylamine (NH 2 OH)) was added to water (5 ml) and dichloromethane (12 ml, 0.1 L/mol) in a 25 ml eggplant flask. was added, and then a 25% sodium hydroxide aqueous solution (about 20 g, 128 mmol, 110 mol %) was added while stirring under ice-cooling until the pH reached 6.9.
  • the reaction formula is the same as in Example 33.
  • Hydroxylamine sulfate (9.56 g, 117 mmol as hydroxylamine (NH 2 OH), 100 mol% as hydroxylamine (NH 2 OH)) was added to water (12 ml) and dichloromethane (12 ml, 0.1 L/mol) in a 25 ml eggplant flask. was added, and aqueous ammonia (7.09 g, purity 28%, 117 mmol, 100 mol %) was added while stirring under ice-cooling. 3-Methyl-2-butenal (10.2 g, purity 98% (GC area %), 119 mmol, 102 mol %) was added thereto so as not to exceed 30°C, and the mixture was stirred at room temperature for 1 hour. The resulting mixture was partitioned into organic and aqueous layers. The organic and aqueous layers were separated. The aqueous layer was extracted with a small amount of dichloromethane.
  • the reaction formula is the same as in Example 38.
  • Example 38 The reaction and analysis were carried out in the same manner as in Example 38, except that the organic solvent, amount of hydroxylamine used, catalyst and stirring conditions (aging conditions) were changed as shown in Table 3. Table 3 shows the results. In addition, the results of Example 38 are also summarized in Table 3.
  • Trifluoroacetic acid (0.29 g, 2.53 mmol, 35 mol%) and N-methylaniline (0.09 g, 0.87 mmol, 12 mol%) were added and stirred at 50°C for 24 hours.
  • the target components excluding the solvent etc. in the reaction mixture were as follows; 5,5-dimethyl-4,5-dihydroisoxazole (target product (7-a)): 80%.
  • the reaction formula is the same as in Example 45.
  • Example 45 The reaction and analysis were carried out in the same manner as in Example 45, except that the addition of the oximating agent and neutralizing agent was changed.
  • the results of Examples 45-48 are shown in Table 4.
  • the reaction formula is the same as in Example 33.
  • Example 49 The reaction and analysis were carried out in the same manner as in Example 49, except that the acid catalyst, base catalyst, solvent, temperature and reaction time were changed.
  • the results of Examples 49-54 are shown in Table 5.
  • 3-methyl-2-butenol (11.45 g, 133 mmol, 100 mol%) and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (916 mg, 5.32 mmol, 4 mol%) was dissolved in 50 mL of butyl acetate to prepare a solution.
  • a solution was prepared by dissolving iron (III) chloride (215 mg, 1.33 mmol, 1 mol%) and 69% nitric acid aqueous solution (607 mg, 6.64 mmol, 5.0 mol%) in 50 mL of butyl acetate under a nitrogen atmosphere. bottom.
  • reaction tube part inner diameter 1 mm, length 20 m
  • reaction tube part inner diameter 1 mm, length 20 m
  • the two raw material solutions prepared above were flowed at a flow rate of After being fed to a Y-tube mixer at 0.05 mL/min and mixed, it was fed to a reaction tube heated to 80° C., and oxygen gas was supplied at 3.15 mL/min at the same time.
  • a reaction mixture was sampled from the outlet of a pressure regulating valve attached to the outlet of the reaction tube, and GC analysis (area percentage) of the reaction mixture was performed. The results of the analysis were as follows; 3-methyl-2-butenal (target product (4-a)): 96%. 3-methyl-2-butenoic acid (side product (10-a)): N.D. .
  • the apparatus used is shown in FIG.
  • Butyl acetate (38.0 mL, 0.38 L/mol) and 69% nitric acid (9.13 g, 100 mmol, 100 mol%) were added to a 200 mL four-necked flask, and iron chloride was added while stirring at 60°C.
  • (III) (162 mg, 1.0 mmol, 1.0 mol%), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (345 mg, 2.0 mmol, 2.0 mol %) and 3-methyl-2-butenol (8.61 g, 100 mmol, 100 mol %) were added in order. After that, the gas generated at the same temperature was collected.
  • 3-Methoxy-3-methylbutanol (20.00 g, 169.23 mmol, 100 mol%) was dissolved in dichloromethane (169.23 ml, 1.0 L/mol) in a 500 mL four-necked flask, followed by tetrabutylammonium bromide. (0.55 g, 1.69 mmol, 1 mol%), 2,2,6,6-tetramethylpiperidine 1-oxyl (0.026 g, 0.17 mmol, 0.1 mol%), phosphoric acid (1.95 g, 16 .92 mmol, 10 mol %) was added.
  • Iron (III) nitrate nonahydrate 101 mg, 0.25 mmol, 0.5 mol%) and 2,2'-bipyridyl (39 mg, 0.25 mmol, 0.5 mol%) were added to a 50 mL eggplant-shaped flask.
  • 2,2,6,6-tetramethylpiperidine 1-oxyl 55 mg, 0.35 mmol, 0.7 mol%)
  • N-bromosuccinimide 53 mg, 0.30 mmol, 0.6 mol%
  • the reaction formula is the same as in Example 15. (The reaction and analysis were performed in the same manner as in Example 24, except that the reaction temperature in Example 24 was changed to 20°C.)
  • Butyl acetate (112.9 mL, 0.75 L/mol), iron (III) chloride (490 mg, 3.0 mmol, 2.0 mol%), 4-hydroxy-2,2 were placed in a 200 mL four-necked flask. , 6,6-tetramethylpiperidine 1-oxyl (1.03 g, 6.0 mmol, 4.0 mol%), 3-methyl-2-butenol (12.92 g, 150 mmol, 100 mol%) Then, while stirring at 20° C., 69% nitric acid (6.85 g, 75 mmol, 50 mol %) was added dropwise over 5 hours, and 5 vol % oxygen-containing nitrogen was added at 20 mL/min.
  • the present invention provides novel methods for producing compounds of formula (3), compounds of formula (4), and compounds of formula (7), which are useful as intermediates for the production of pharmaceuticals, agricultural chemicals, and the like.
  • the production method of the present invention is economical and environmentally friendly, and has high industrial utility value. Therefore, the present invention has high industrial applicability.

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US20230150913A1 (en) * 2021-11-12 2023-05-18 Samuel J. Rozzoni Synthesis of novel ketone body analogs for use as a nutritional supplement

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5136102A (en) * 1991-10-18 1992-08-04 Shell Oil Company Process for the preparation of ketones
US5155279A (en) * 1991-10-18 1992-10-13 Shell Oil Company Process for the oxidation of alcohols to aldehydes
JP2006176527A (ja) * 2004-12-23 2006-07-06 Degussa Ag 安定なニトロキシルフリーラジカルを用いる温和条件下でのアルコールの遷移金属を含まない有酸素性の触媒酸化方法
JP2013518064A (ja) * 2010-07-26 2013-05-20 華東師範大学 酸素でアルコールを酸化する、アルデヒド或いはケトンの製造方法
WO2020156238A1 (zh) * 2019-01-29 2020-08-06 复旦大学 铜催化的以氧气为氧化剂氧化醇制备醛或酮类化合物的方法和应用
WO2020251006A1 (ja) * 2019-06-14 2020-12-17 クミアイ化学工業株式会社 ジヒドロイソキサゾールの製造方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5136102A (en) * 1991-10-18 1992-08-04 Shell Oil Company Process for the preparation of ketones
US5155279A (en) * 1991-10-18 1992-10-13 Shell Oil Company Process for the oxidation of alcohols to aldehydes
JP2006176527A (ja) * 2004-12-23 2006-07-06 Degussa Ag 安定なニトロキシルフリーラジカルを用いる温和条件下でのアルコールの遷移金属を含まない有酸素性の触媒酸化方法
JP2013518064A (ja) * 2010-07-26 2013-05-20 華東師範大学 酸素でアルコールを酸化する、アルデヒド或いはケトンの製造方法
WO2020156238A1 (zh) * 2019-01-29 2020-08-06 复旦大学 铜催化的以氧气为氧化剂氧化醇制备醛或酮类化合物的方法和应用
WO2020251006A1 (ja) * 2019-06-14 2020-12-17 クミアイ化学工業株式会社 ジヒドロイソキサゾールの製造方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230150913A1 (en) * 2021-11-12 2023-05-18 Samuel J. Rozzoni Synthesis of novel ketone body analogs for use as a nutritional supplement
US11807600B2 (en) * 2021-11-12 2023-11-07 Samuel J. Rozzoni Synthesis of novel ketone body analogs for use as a nutritional supplement

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