Classifications

• • 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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
  • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
  • C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
• • 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
  • C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation

Definitions

• the present invention has the formula (5):
• R 1 and R 2 are as described below, that is, a method for producing dihydroisoxazole.
• Patent Document 1 discloses a useful herbicide. Among them, Pyroxasulfone is well known as a herbicide having excellent herbicidal activity. Further, Patent Document 2 discloses that the compound of the formula (5) is an important intermediate of the herbicide described in Patent Document 1.
• Patent Document 2 discloses a method for producing 5,5-di-substituted-4,5-dihydroisoxazole.
• Non-Patent Documents 1 and 2 disclose a method for producing a 4,5-dihydroisoxazole derivative using ketooxime.
• the present inventor has diligently studied the method for producing the compound of the formula (5). As a result, it was surprisingly found that the above-mentioned problems can be solved by providing the following method for producing the compound of the formula (5). The present inventor has completed the present invention based on this finding.
• the present invention is as follows.
• R 1 and R 2 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; or optionally substituted phenyl; or R 1 and R 2 are with the carbon atom to which they are attached. Together, they form a 4- to 12-membered carbocycle, which may be substituted.)
• a method for producing the compound of the above which comprises the following steps (i) and (ii): Step (i) (Oximelation step) A step of reacting the compound of the formula (2) with an oxime agent to produce the compound of the formula (3):
• R 1 and R 2 are as defined above;
• R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; optionally substituted (C2-C6) alkenyl; substituted It may be (C2-C6) alkynyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl.
• Step (ii) (cyclization step) A step of reacting the compound of the formula (3) to produce the compound of the formula (5):
• R 1, R 2 and R 3 are as defined above.
• step (i) The method according to [I-1], wherein the oxime agent in step (i) is an aqueous hydroxylamine solution, hydroxylamine hydrochloride or hydroxylamine sulfate.
• step (i) The method according to [I-1], wherein the oxime agent in step (i) is a 45% to 50% aqueous solution of hydroxylamine, hydroxylamine hydrochloride or hydroxylamine sulfate.
• R 4 and R 5 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl. ), The method according to [I-2].
• R 4 and R 5 of the formula (6) are independently hydrogen atoms; (C1-C6) alkyl; (C3-C6) cycloalkyl; or (C6-C10) aryl.
• step (i) The amount of the oxime agent used in step (i) is 0.9 to 1.5 mol in terms of hydroxylamine (NH 2 OH) with respect to 1 mol of the compound of the formula (2).
• the amount of the oxime agent used in the step (i) is 1.0 to 1.3 mol in terms of hydroxylamine (NH 2 OH) with respect to 1 mol of the compound of the formula (2).
• the amount of the neutralizing agent used is 0.5 to 1.5 mol (preferably 0.9 to 1.5 mol) with respect to 1 mol of the compound of the formula (2).
• step (i) consists of one or more (preferably one or two, more preferably one) solvent selected from acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, and dichloromethane.
• solvent selected from acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, and dichloromethane.
• the reaction in step (i) is one or more (preferably one or two, more preferably one) solvent selected from toluene, xylene, chlorobenzene, dichlorobenzene, and dichloromethane, and an aqueous solvent.
• solvent selected from toluene, xylene, chlorobenzene, dichlorobenzene, and dichloromethane, and an aqueous solvent.
• step (i) The reaction of step (i) is carried out in the presence of one or more (preferably one or two, more preferably one) solvent selected from toluene and dichloromethane, and an aqueous solvent.
• one or more solvent selected from toluene and dichloromethane selected from toluene and dichloromethane
• an aqueous solvent selected from toluene and dichloromethane
• step (i) Any of [I-1] to [I-19], wherein the reaction of step (i) is carried out in the presence of a solvent of a combination of water and dichloromethane (that is, a mixed solvent of water and dichloromethane).
• a solvent of a combination of water and dichloromethane that is, a mixed solvent of water and dichloromethane.
• [I-29] One or more (preferably 1 to 3, more preferably 1 or 2) acid catalysts selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids, phosphoric acids, solid acids and Lewis acids.
• [I-30] One or more (preferably 1 to 3, more preferably 1 to 3) acid catalysts selected from the group consisting of mineral acids but hydrochloric acid, carboxylic acids, sulfonic acids, phosphoric acids, solid acids and Lewis acids.
• Acid catalysts are hydrochloric acid, sulfuric acid, nitrate, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, transition metal triflate, And one or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acid catalysts selected from the group consisting of Nafion, [I-27] or [I-28]. The method described in.
• Acid catalysts are sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, transition metal triflate, and naphthion.
• Acid catalysts are hydrochloric acid, sulfuric acid, nitrate, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, scandium (III) trif.
• Acid catalysts are sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, scandium (III) trifrate, One or more (preferably 1-3, more preferably 1 or 2, even more preferably 1) acid catalysts selected from the group consisting of itterbium (III) triflate and naphthone [I-27]. ] Or [I-28].
• [I-35] One or more acid catalysts selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, and naphthion (1 or more).
• [I-36] One or more acids (preferably 1 to 3, more preferably 1 or 2, and even more preferably 1) selected from the group consisting of nitric acid, trifluoroacetic acid, and maleic acid as the acid catalyst.
• acids preferably 1 to 3, more preferably 1 or 2, and even more preferably 1 selected from the group consisting of nitric acid, trifluoroacetic acid, and maleic acid as the acid catalyst.
• the acid catalyst is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1) acid catalyst selected from the group consisting of trifluoroacetic acid and maleic acid.
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1 or 2) selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids and phosphoric acids. 1) Acid, according to [I-27] or [I-43].
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2) selected from the group consisting of mineral acids, but hydrochloric acid, carboxylic acids, sulfonic acids and phosphoric acids.
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1) acid selected from the group consisting of carboxylic acids and sulfonic acids.
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2) selected from the group consisting of trifluoroacetic acid, maleic acid, and p-toluenesulfonic acid.
• the amount of the acid used in the acid-base catalyst is 0.01 to 0.60 mol with respect to 1 mol of the compound of the formula (1).
• the amount of the acid used in the acid-base catalyst is 0.05 to 0.40 mol with respect to 1 mol of the compound of the formula (1).
• the acid-base catalyst base is one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) secondary amine or heterocyclic amine.
• the method according to any one of [I-27] or [I-43] to [I-49].
• the amount of the base used in the acid-base catalyst is 0.01 to 0.60 mol with respect to 1 mol of the compound of the formula (1).
• the amount of the base used in the acid-base catalyst is 0.05 to 0.40 mol with respect to 1 mol of the compound of the formula (1).
• the reaction in step (ii) is one or more (preferably one or two, more preferably 1) selected from acetone, acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, water and ionic liquids.
• step (ii) is one or more (preferably 1 or 2, more preferably 1) selected from acetone, acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, water and BMIMCF 3.
• Step (pre-i) A step of reacting a compound of formula (1) with an oxidizing agent to produce a compound of formula (2):
• R 1, R 2 and R 3 are as defined above.
• step (i) is carried out without isolating the compound of the formula (2) produced in the step (pre-i). The method described.
• the reaction of the step (pre-i) is one or more (preferably one or two, more preferably one) solvent selected from toluene, xylene, chlorobenzene, dichlorobenzene and dichloromethane, and water.
• solvent selected from toluene, xylene, chlorobenzene, dichlorobenzene and dichloromethane, and water.
• step (pre-i) The reaction in step (pre-i) is carried out in the presence of one or more (preferably one or two, more preferably one) solvent selected from toluene, xylene and dichloromethane, and an aqueous solvent.
• one or more solvent selected from toluene, xylene and dichloromethane, and an aqueous solvent.
• the buffer solution is phosphoric acid, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen carbonate, potassium hydrogen carbonate, acetic acid or sodium acetate. , [I-83].
• phase transfer catalyst is a quaternary ammonium salt, a quaternary phosphonium salt or crown ethers.
• phase transfer catalyst is tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hydrogen sulfate, tetrabutylphosphonium bromide or 12-crown-4.
• phase transfer catalyst is tetrabutylammonium bromide.
• Copper catalyst is copper bromide (II), copper sulfate (II), copper acetate (II), copper oxide (I), copper trifluoromethanesulfonate (II) or copper (II) nitrate 3 water.
• [I-96] Either 1 of [I-94] or [I-95], wherein the amount of the copper catalyst used is 0.001 to 0.01 mol with respect to 1 mol of the compound of the formula (1). The method described in the section.
• R 1 and R 2 are independently (C1-C6) alkyl; (C1-C6) haloalkyl; (C3-C6) cycloalkyl; (C2-C6) alkenyl; (C2-C6). ) Alkinyl; or phenyl which may be substituted with 1-5 substituents independently selected from (C1-C4) alkyl and (C1-C4) haloalkyl; or R 1 and R 2 are The method according to any one of [I-1] to [I-96], wherein they form a 4- to 6-membered carbocycle together with the carbon atoms to which they are bonded.
• R 1 and R 2 are independently (C1-C4) alkyl; (C1-C4) haloalkyl; (C3-C6) cycloalkyl; (C2-C4) alkenyl; (C2-C4). ) Alkinyl; or a phenyl optionally substituted with 1-5 substituents independently selected from (C1-C4) alkyl and (C1-C4) haloalkyl; or R 1 and R 2 are.
• R 1 and R 2 are each independently, (C1-C4) alkyl, [I-1] - The method according to any one of [I-96].
• R 1 and R 2 are methyl groups [I-1] - The method according to any one of [I-96].
• R 3 is a hydrogen atom; or (C1-C4) The method according to any one of an alkyl [I-1] - [I-101].
• R 3 is a hydrogen atom or a methyl group [I-1] - The method according to any one of [I-101].
• R 1 and R 2 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; or optionally substituted phenyl; or R 1 and R 2 are with the carbon atom to which they are attached. Together, they form a 4- to 12-membered carbocycle, which may be substituted.) It is a method for producing the compound of A method comprising the step of reacting the compound of the cyclization step (3) to produce the compound of the formula (5):
• R 1 and R 2 are as defined above;
• R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; optionally substituted (C2-C6) alkenyl; substituted It may be (C2-C6) alkynyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl. ).
• [II-5] One or more (preferably 1 to 3, more preferably 1 to 3) acid catalysts selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids, phosphoric acids, solid acids and Lewis acids in the cyclization step.
• acid catalysts selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids, phosphoric acids, solid acids and Lewis acids in the cyclization step.
• [II-6] One or more (preferably 1 to 3) acid catalysts in the cyclization step selected from the group consisting of mineral acids except hydrochloric acid, carboxylic acids, sulfonic acids, phosphoric acids, solid acids and Lewis acids. , More preferably one or two, and even more preferably one) acid catalyst, according to [II-3] or [II-4].
• the acid catalyst in the cyclization step is hydrochloric acid, sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, transition.
• the acid catalyst in the cyclization step is sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, transition metal trif.
• the acid catalyst in the cyclization step is hydrochloric acid, sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, scandium.
• acid catalyst selected from the group consisting of (III) triflate, itterbium (III) triflate, and naphthone.
• the acid catalyst in the cyclization step is sulfuric acid, nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, phosphoric acid, scandium (III). ) One or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acid catalysts selected from the group consisting of triflate, itterbium (III) triflate, and naphthon. The method according to [II-3] or [II-4].
• the acid catalyst in the cyclization step is selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic acid anhydride, maleic acid, maleic anhydride, dodecylbenzenesulfonic acid, p-toluenesulfonic acid, and naphthion.
• the acid catalyst in the cyclization step is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1) selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid.
• the acid catalyst in the cyclization step is one or more selected from the group consisting of trifluoroacetic acid and maleic acid (preferably 1 to 3, more preferably 1 or 2, and even more preferably 1).
• the amount of the acid catalyst used in the cyclization step is 0.01 to 0.60 mol with respect to 1 mol of the compound of the formula (3), from [II-3] to [II-16].
• the amount of the acid catalyst used in the cyclization step is 0.05 to 0.40 mol with respect to 1 mol of the compound of the formula (3), from [II-3] to [II-16].
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1 or 2) selected from the group consisting of mineral acids, carboxylic acids, sulfonic acids and phosphoric acids.
• [II-21] One or more (preferably 1 to 3, more preferably 1 or 2) acid-base catalyst acids selected from the group consisting of mineral acids except hydrochloric acid, carboxylic acids, sulfonic acids, and phosphoric acids.
• acid-base catalyst acids selected from the group consisting of mineral acids except hydrochloric acid, carboxylic acids, sulfonic acids, and phosphoric acids.
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2, more preferably 1) acid selected from the group consisting of carboxylic acids and sulfonic acids.
• the acid-base catalyst acid is one or more (preferably 1 to 3, more preferably 1 or 2) selected from the group consisting of trifluoroacetic acid, maleic acid, and p-toluenesulfonic acid.
• the amount of acid used in the acid-base catalyst is 0.01 to 0.60 mol with respect to 1 mol of the compound of the formula (1), [II-3] or [II-19] to The method according to any one of [II-25].
• the amount of the acid used in the acid-base catalyst is 0.05 to 0.40 mol with respect to 1 mol of the compound of the formula (1), [II-3] or [II-19] to The method according to any one of [II-25].
• the acid-base catalyst base is one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) secondary amine or heterocyclic amine.
• the amount of the base used in the acid-base catalyst is 0.01 to 0.60 mol with respect to 1 mol of the compound of the formula (1), [II-3] or [II-19] to The method according to any one of [II-30].
• the amount of the base used in the acid-base catalyst is 0.05 to 0.40 mol with respect to 1 mol of the compound of the formula (1), [II-3] or [II-19] to The method according to any one of [II-30].
• [II-33] One or more (preferably one or two, more preferably one) reaction in the cyclization step selected from acetone, acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, water and ionic liquids. ), The method according to any one of [II-1] to [II-32].
• [II-34] One or more (preferably one or two, more preferably one) reaction in the cyclization step selected from acetone, acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, water and BMIMCF 3. ), The method according to any one of [II-1] to [II-32].
• R 1 and R 2 are independently (C1-C6) alkyl; (C1-C6) haloalkyl; (C3-C6) cycloalkyl; (C2-C6) alkenyl; (C2-C6). ) Alkinyl; (C1-C6) alkoxy; or phenyl which may be substituted with 1-5 substituents independently selected from (C1-C4) alkyl and (C1-C4) haloalkyl; Alternatively, R 1 and R 2 , together with the carbon atoms to which they are bonded, form a 4- to 6-membered carbocycle, according to any one of [II-1] to [II-39]. The method described.
• R 1 and R 2 are independently (C1-C4) alkyl; (C1-C4) haloalkyl; (C3-C6) cycloalkyl; (C2-C4) alkenyl; (C2-C4). ) Alkinyl; (C1-C4) alkoxy; or phenyl which may be substituted with 1-5 substituents independently selected from (C1-C4) alkyl and (C1-C4) haloalkyl; Alternatively, R 1 and R 2 , together with the carbon atoms to which they are bonded, form a 4- to 6-membered carbocycle, according to any one of [II-1] to [II-39]. The method described.
• R 1 and R 2 each independently, (C1-C4) alkyl or (C1-C4) haloalkyl, in any one of [II-1] - [II-39] The method described.
• R 1 and R 2 are each independently, (C1-C4) alkyl, A method according to any one of [II-1] - [II-39].
• R 1 and R 2 are methyl groups [II-1] a method according to any one of - [II-39].
• R 3 is a hydrogen atom; (C1-C4) alkyl; or (C1-C4) The method according to any one of a haloalkyl [II-1] - [II-44].
• R 3 is a hydrogen atom; or (C1-C4) The method according to any one of an alkyl [II-1] - [II-44].
• R 3 is a hydrogen atom or a methyl group [II-1] a method according to any one of - [II-44].
• R 1 and R 2 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; or optionally substituted phenyl; or R 1 and R 2 are with the carbon atom to which they are attached.
• Step (i) (Oximelation step) A step of reacting the compound of the formula (2) with an oxime agent to produce the compound of the formula (3):
• R 1 and R 2 are as defined above;
• R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; optionally substituted (C2-C6) alkenyl; substituted It may be (C2-C6) alkynyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl.
• Step (ii) (Cyclation step) A step of reacting the compound of the formula (3) to produce the compound of the formula (5):
• R 4 and R 5 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl. ), The method according to [III-2].
• Step (pre-i) A step of reacting a compound of formula (1) with an oxidizing agent to produce a compound of formula (2): (Wherein, R 1, R 2 and R 3 are as defined above.).
• step (i) is carried out without isolating the compound of the formula (2) produced in the step (pre-i). The method described.
• R 1 and R 2 are independently hydrogen atoms; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. May be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; or optionally substituted phenyl; or R 1 and R 2 are with the carbon atom to which they are attached.
• R 1 and R 2 are as defined above.
• R 3 is a hydrogen atom; optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; optionally substituted (C2-C6) alkenyl; substituted It may be (C2-C6) alkynyl; optionally substituted (C6-C10) aryl; or optionally substituted (C6-C10) aryl (C1-C4) alkyl. ).
• [III-15] An acid selected from the group consisting of mineral acids, carboxylic acids, and sulfonic acids, and a base selected from the group consisting of primary amines, secondary amines, and heterocyclic amines.
• R 1 and R 2 are methyl groups [III-1] - The method according to any one of [III-16].
• R 3 is (C1-C4) alkyl [III-1] - The method according to any one of [III-17].
• R 3 is a methyl group [III-1] - The method according to any one of [III-17].
• the present invention provides a novel method for producing the compound of the formula (5). According to the present invention, there is provided a more industrially preferable method for producing a compound of the formula (5). Further, according to the present invention, the compound of the formula (5) can be produced in a high yield by a simple operation.
• the present invention has provided a method capable of easily and inexpensively producing an intermediate for producing a herbicide such as pyroxasulfone on an industrial scale. Therefore, the method of the present invention is industrially preferable, economical, environmentally friendly, and has high industrial utility value.
• 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)" of "(C1-C4) alkyl” means that the number of carbon atoms of the alkyl is 1 to 4.
• alkyl is understood to include both straight and branched chains such as butyl and tert-butyl.
• a specific term such as “butyl” is used, it is specific for "normal butyl", i.e. "n-butyl”.
• the specific term “butyl” means linear "normal butyl”.
• branched chain isomers such as “tert-butyl” are specifically mentioned when intended.
• n-", "s-" and “sec-”, “i-”, “t-” and “tert-”, [neo-], "c-” and “cyc-”, “o-” , “M-”, and “p-” have the following usual meanings: normal, secondary ("s-” and “sec-"), iso, tertiary ("t-” and “t-”). 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 ie, normal hexyl (ie, normal hexyl).
• Dec 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.
• Ms means methylsulfonyl (CH 3 SO 2- ).
• Ts means tosyl (4-CH 3- C 6 H 4 SO 2- ).
• Tf means trifluoromethylsulfonyl (CF 3 SO 2- ).
• Ac means acetyl (CH 3 CO-).
• (C1-C6) alkyl means a linear or branched chain 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 chain alkyl having 1 to 4 carbon atoms.
• the example of (C1-C4) alkyl is a suitable example of the above examples of (C1-C6) alkyl.
• Haloalkyl means a linear or branched chain alkyl having 1 to 6 carbon atoms substituted with the same or different 1 to 13 halogen atoms (wherein the halogen atom is It has the same meaning as the above definition.)
• Examples of (C1-C6) haloalkyl include fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoro.
• Haloalkyl means a linear or branched chain alkyl having 1 to 4 carbon atoms substituted with the same or different 1 to 9 halogen atoms (wherein the halogen atom is the above). Has the same meaning as the definition of).
• Examples of (C1-C4) haloalkyl include, but are not limited to, suitable examples of the above (C1-C6) haloalkyl examples.
• Cycloalkyl means a cycloalkyl having 3 to 6 carbon atoms.
• Examples of (C3-C6) cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
• (C2-C6) alkenyl means a straight chain or branched chain alkenyl having 2 to 6 carbon atoms.
• Examples of (C2-C6) alkenyl include vinyl, 1-propenyl, isopropenyl, 2-propenyl, 1-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-butenyl, 1,3. -Including, but not limited to, butazienyl, 1-pentenyl, 1-hexenyl and the like.
• (C2-C4) alkenyl means a straight-chain or branched-chain alkenyl having 2 to 4 carbon atoms.
• Examples of (C2-C4) alkenyl include, but are not limited to, suitable examples of the above examples of (C2-C6) alkenyl.
• (C2-C6) alkynyl means a linear or branched alkynyl having 2 to 6 carbon atoms.
• Examples of (C2-C6) alkynyls include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 2-butynyl, 1-pentynyl, 1-hexynyl and the like. Not limited.
• (C2-C4) alkynyl means a linear or branched alkynyl having 2 to 4 carbon atoms.
• Examples of (C2-C4) alkynyl include, but are not limited to, suitable examples of the above examples of (C2-C6) alkynyl.
• (C1-C6) alkoxy means (C1-C6) alkyl-O- (where the (C1-C6) alkyl moiety has the same meaning as defined above).
• Examples of (C1-C6) alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy and the like. Not limited to.
• (C1-C4) alkoxy means (C1-C4) alkyl-O- (where the (C1-C4) alkyl moiety has the same meaning as defined above).
• Examples of (C1-C4) alkoxy include, but are not limited to, suitable examples of the above (C1-C6) alkoxy examples.
• Examples of (C6-C10) aryls are phenyl, 1-naphthyl, and 2-naphthyl.
• (C6-C10) aryl (C1-C4) alkyl means (C1-C4 alkyl) substituted with (C6-10) aryl (where the C6-10 aryl moiety and the C1-C4 alkyl moiety are It has the same meaning as the above definition.)
• Examples of (C6-C10) aryl (C1-C4) alkyls are benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, naphthalene-1-ylmethyl, naphthalene-2-ylmethyl groups. Etc., but are not limited to these.
• the 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 3-14 members (preferably 5-14 members, more preferably). Includes, but is not limited to, 5-10 member) cyclic hydrocarbon groups.
• examples of cyclic hydrocarbon groups are aromatic or non-aromatic, monocyclic or bicyclic (preferably monocyclic) 4-8 members (preferably 5-6 members). Includes, but is 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-condensed cyclic (eg, monocyclic or spirocyclic) and fused cyclic cyclic groups, if possible. ..
• the cyclic hydrocarbon group as defined or exemplified above may be unsaturated, partially saturated or saturated, if possible.
• the cyclic hydrocarbon group as defined or exemplified above is also called a carbocyclic group.
• the carbon ring is a ring corresponding to a cyclic hydrocarbon group as defined or exemplified above.
• substituted in the term “may be substituted” is not particularly limited as long as they are chemically acceptable and show the effect of the present invention.
• substituted examples include one or more substituents (preferably 1 to 4) independently selected from the substituent group (a). Substituents), but are not limited to these.
• the substituent group (a) includes a halogen atom; a nitro group; a cyano group; a hydroxy group; an amino group; (C1-C6) alkyl; (C1-C6) haloalkyl; (C3-C6) cycloalkyl; (C2-C6).
• one or more substituents independently selected from the substituent group (a) are selected independently from the substituent group (b). It may have one or more substituents (preferably 1 to 4 substituents).
• substituent group (b) is the same as the substituent group (a).
• compounds having isomers include all isomers and any mixture thereof in any proportion.
• xylene comprises o-xylene, m-xylene, p-xylene and any mixture thereof in any proportion.
• dichlorobenzene comprises o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene and any mixture thereof in any proportion.
• the wavy line in the chemical formula means the following.
• a geometric isomer that is, E / Z isomer
• E cis-trans isomer
• Z Z
• Isomers any proportion of their mixture are included in the chemical formula with wavy lines.
• Step (i) The step (i) will be described.
• the reaction in step (i) is oxime formation.
• the reaction in step (i) is also referred to as an oxime formation step.
• the step (i) is a step of reacting the compound of the formula (2) with the oxime agent to produce the compound of the formula (3).
• the compound of the formula (2) is used as the raw material of the step (i).
• the compound of the formula (2) is a known compound, or can be produced from a known compound according to a known method.
• Specific examples of the compound of formula (2) include, but are not limited to, 3-hydroxy-3-methylbutanal (also referred to as 3-hydroxy-3-methyl-butane-1-ar),.
• the oxime agent used in step (i) may be any oxime agent as long as the reaction proceeds.
• oxime agents that can be used in step (i) include hydroxylamines, hydroxylamine salts and oxime compounds.
• the oxime 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, such as hydroxylamine hydrochloride, hydroxylamine sulfate, hydroxylamine nitrate (eg, 50% aqueous solution), hydroxylamine carbonate, hydroxylamine phosphate, hydroxylamine acetate, hydroxylamine oxalate, etc. Not limited.
• the oxime compound as an oxime agent is represented by the following formula.
• R 4 and R 5 are independently hydrogen atoms; (C1-C6) alkyl; (C3-C6) cycloalkyl; (C2-C6) alkenyl; (C2-C6) alkynyl; (C6-C6-). C10) aryl; or (C6-C10) aryl (a C1-C4) alkyl, or R 4 and R 5, two may combine with each other to form a ring.
• the compound of the formula (6) is a known compound, or can be produced from a known compound according to a known method.
• R 4 and R 5 of the compound of formula (2) do not form a ring include, but are not limited to: Form oxime, acetone oxime, 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-nonanonone oxime, acetoaldoxime, benzoaldoxime, acetophenone oxime, 4'-hydroxyacetophenone oxime, benzophenone oxime, etc. Be done.
• R 4 and R 5 of the compound of formula (2) forming a non-conjugated ring include, but are not limited to: Cyclopropanone oxime, cyclobutanone oxime, cyclopentanone oxime, cyclohexanone oxime, cycloheptanone oxime, cyclooctanone oxime, cyclononanonone oxime, cyclodecanone oxime and the like can be mentioned.
• the oxime agent used in the step (i) may be used alone or in a combination of two or more kinds at an arbitrary ratio.
• the form of the oxime agent used in step (i) may be any form as long as the reaction proceeds and safety is ensured. To the extent that the reaction proceeds and safety is ensured, examples of its forms include solids and liquids, as well as aqueous solutions of arbitrary concentrations and solutions of solvents other than water (eg, organic solvents).
• the form of hydroxylamine may be any form as long as the reaction proceeds and safety is ensured.
• preferable examples of the form of hydroxylamine (free) include an aqueous solution having a concentration of 10% or more and less than 70%, preferably an aqueous solution having a concentration of 45% or more and 55% or less.
• the amount of the oxime agent used in step (i) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., in one embodiment, 1 mol of the compound of the formula (2) is converted into hydroxylamine (NH 2 OH) from 0.9 to 1. The range of 5 equivalents, preferably 0.9 to 1.3 equivalents, can be exemplified. In another embodiment, 1 mol of the compound of formula (2) is converted to hydroxylamine (NH 2 OH) in the range of 1.0 to 1.5 equivalents, preferably 1.0 to 1.3 equivalents. Can also be exemplified. However, the amount used can be appropriately adjusted by those skilled in the art.
• converted to hydroxylamine is as follows. For example, 1 mol of NH 2 OH ⁇ HCl is converted to 1 mol of NH 2 OH. As another example, 1 mole of (NH 2 OH) 2 ⁇ H 2 SO 4 is converted to 2 moles of NH 2 OH. As yet another example, 1 mole of acetone oxime is converted to 1 mole of NH 2 OH.
• a hydroxylamine salt for example, hydroxylamine hydrochloride, hydroxylamine sulfate, etc.
• the reaction in step (i) is preferably carried out using a neutralizing agent.
• Neutralizers are bases for neutralizing hydroxylamine salts to liberate free hydroxylamine. Examples of neutralizers are alkali metal hydroxides (eg, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal hydroxides (eg, magnesium hydroxide, calcium hydroxide, water).
• alkali metal carbonates eg, lithium carbonate, sodium carbonate, potassium carbonate, etc.
• alkaline earth metal carbonates eg, magnesium carbonate, calcium carbonate, barium carbonate, etc.
• alkali metal hydrogen carbonates eg, magnesium carbonate, etc.
• alkali metal carboxylates eg, lithium acetate, sodium acetate, potassium acetate, etc.
• amines eg, triethylamine, tributylamine, diisopropylethylamine, 1,8 -Diazabicyclo [5.4.0] -7-Undec-7-ene (DBU), pyridine, etc.
• ammonia eg, 25-30% aqueous ammonia, ammonia gas, preferably 25-30% aqueous ammonia).
• the neutralizing agent are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate and the like, ammonia, more preferably sodium hydroxide, sodium carbonate, sodium hydrogencarbonate, ammonia, etc. More preferably, it contains sodium hydroxide.
• sodium hydroxide include sodium hydroxide beads, 48% sodium hydroxide aqueous solution, 25% sodium hydroxide aqueous solution, 10% sodium hydroxide aqueous solution, preferably 48% sodium hydroxide aqueous solution, 25% sodium hydroxide aqueous solution, and more. It preferably comprises, but is not limited to, a 48% aqueous sodium hydroxide solution.
• the neutralizer may be used alone or in any combination of two or more at any ratio.
• the form of the neutralizing agent may be any form as long as the reaction proceeds. Examples of such forms include solids, liquids and gases containing only neutralizers, and solutions of aqueous solutions of arbitrary concentrations and solvents other than water (eg, organic solvents).
• 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 (i) 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 1.5 mol, more preferably 0.5 mol, based on 1 mol of the compound of the formula (2). The range of 0.8 to 1.5 mol, more preferably 1.0 to 1.3 mol can be exemplified.
• solvent of step (i) From the viewpoint of smooth progress of the reaction, safety and the like, the reaction of step (i) is preferably carried out in the presence of a solvent.
• the solvent may be any solvent as long as the reaction of step (i) proceeds and safety is ensured.
• solvents include water, alcohols (eg, methanol, ethanol, 2-propanol, butanol, tert-butanol (tert-butanol is also referred to as tert-butyl alcohol), etc.), ethers (eg, tetrahydrofuran (THF), etc.).
• 1,4-dioxane diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, 1,2-dimethoxyethane (DME), diglycyme, triglyme Etc.), nitriles (eg, acetonitrile, etc.), amides (eg, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), alkylureas (For example, N, N'-dimethylimidazolidinone (DMI), etc.), sulfoxides (for example, dimethyl sulfoxide (DMSO), etc.), sulfones (for example, sulfolane, etc.), carboxylic acid esters (for example, ethyl acetate, etc.)
• preferred examples of the solvent in step (i) are water, alcohols, nitriles, ethers, aromatic hydrocarbon derivatives, etc.
• Halogenized aliphatic hydrocarbons and any combination thereof in any proportion more preferably water, nitriles, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and any combination thereof in any proportion.
• Preferred specific examples of the solvent in step (i) are water, methanol, ethanol, 2-propanol, tert-butanol, acetonitrile, tetrahydrofuran (THF), toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any proportions.
• any combination thereof more preferably water, acetonitrile, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any combination thereof in any proportion, even more preferably water, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and Includes any combination thereof in any proportion, particularly preferably any combination of water and dichloromethane and water and toluene.
• the presence of water is preferable.
• the solvent may be separated into a single layer or two layers as long as the reaction proceeds.
• preferred examples of the solvent in step (i) are water, alcohols, nitriles, ethers, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and any of them in any proportion.
• Preferred specific examples of the solvent in step (i) are water, methanol, ethanol, 2-propanol, tert-butanol, acetonitrile, tetrahydrofuran (THF), toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane and any proportions.
• Any combination thereof more preferably water, methanol, ethanol, 2-propanol, tert-butanol, acetonitrile, dichloromethane and any combination thereof, more preferably water, acetonitrile, dichloromethane and any proportion.
• Water derived from an aqueous hydroxylamine solution can be understood as a solvent.
• a neutralizing agent eg, hydroxylamine hydrochloride, hydroxylamine sulfate, etc.
• water derived from an aqueous solution of the neutralizing agent eg, 48% aqueous sodium hydroxide solution
• Water produced by neutralization can also be understood as a solvent.
• the amount of the solvent used in step (i) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., 0 (zero) to 10 L (liter), preferably 0.02 to 5 L, more preferably 0, with respect to 1 mol of the compound of the formula (2). The range of 02 to 1 L, more preferably 0.1 to 1 L can be exemplified. However, the amount used can be appropriately adjusted by those skilled in the art. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds. The proportion can be adjusted appropriately by those skilled in the art. The solvent may be separated into a single layer or two layers as long as the reaction proceeds.
• reaction temperature in step (i) The reaction temperature in step (i) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., -30 ° C (-30 ° C) to 160 ° C, preferably -10 ° C to 80 ° C, more preferably 0 ° C to 80 ° C, still more preferably 10 ° C. The range of about 50 ° C., more preferably room temperature (10 ° C. to 35 ° C.) can be exemplified. However, the reaction temperature can be appropriately adjusted by those skilled in the art.
• reaction time of step (i) The reaction time of step (i) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency and the like, a range of 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, and more preferably 0.5 hours to 12 hours can be exemplified. However, the reaction time can be appropriately adjusted by those skilled in the art.
• step (i) The product of step (i) is a compound of formula (3) corresponding to the compound of formula (2) used as a raw material.
• Specific examples include, but are not limited to, 3-hydroxy-3-methylbutanal oxime (also referred to as 3-hydroxy-3-methyl-butane-1-ar oxime), 3-methoxy-3.
• the compound of formula (3) which is a product of step (i), can be used as a raw material for step (ii).
• the compound of the formula (3) obtained in the step (i) may be isolated and used in the next step, may be further purified and used in the next step, or may be used in the next step without being isolated. Good.
• Step (ii) The step (ii) will be described.
• step (ii) is a cyclization reaction.
• the step (ii) is also referred to as a cyclization step.
• the step (ii) is a step of reacting the compound of the formula (3) in the presence of a catalyst to produce the compound of the formula (5).
• the compound of the formula (3) is used as a raw material for the step (ii).
• the compound of the formula (3) is a known compound, or can be produced from a known compound according to a known method.
• the compound of formula (3) can be produced by the method of step (i) above. Specific examples and preferable specific examples of the compound of the formula (3) are as described above.
• the catalyst of step (ii) may be any catalyst as long as the reaction proceeds.
• an acid catalyst or an acid-base catalyst can be used.
• the compound of formula (5) is produced in the presence of an acid catalyst.
• the acid catalyst may be any acid catalyst as long as the reaction proceeds.
• any of the following forms may be used as long as the reaction proceeds and is within the scope of the present invention.
• a free acid can be used as the acid catalyst.
• the acid catalyst may be used in the form of a salt. 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 form of an anhydride.
• the acid catalyst may be used in the form of a hydrate.
• the acid catalyst may be used in the form of a dimer or the like.
• acid catalysts in step (ii) include, but are not limited to:
• Mineral acids can be used as the acid catalyst in step (ii).
• mineral acids include hydrochloric acid, sulfuric acid, nitric acid.
• Carboxylic acids, salts thereof and anhydrides can be used as the acid catalyst in step (ii). Therefore, the carboxylic acid may be used as a free acid or as a salt thereof. In addition, the carboxylic acid may be used as its anhydride.
• examples of carboxylic acids include saturated or unsaturated aliphatic (C1-C8) monocarboxylic acids, dicarboxylic acids and tricarboxylic acids, which may be substituted with one or more halogen atoms, and halogen atoms.
• Examples of preferred carboxylic acids include saturated or unsaturated aliphatic (C1-C8) carboxylic acids that may be substituted with one or more halogen atoms.
• Examples of carboxylic acid salts and carboxylic acid anhydrides are their salts and anhydrides.
• examples of carboxylic acids include saturated or unsaturated aliphatic (C1-C8) carboxylic acids that may be substituted with one or more halogen atoms, as well as halogen atoms, (C1-C4) alkyl and (C1). -C4) Contains benzoic acid, which may be substituted with one or more substituents independently selected from haloalkyl.
• Examples of preferred carboxylic acids include saturated or unsaturated aliphatic (C1-C8) carboxylic acids that may be substituted with one or more halogen atoms.
• Examples of carboxylic acid salts and carboxylic acid anhydrides are their salts and anhydrides.
• carboxylic acids include acetic acid, trifluoroacetic acid, 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.
• Specific examples of carboxylates include ammonium trifluoroacetate (CF 3 COO - NH 4 + )) and N-methylanillium trifluoroacetate (CF 3 COO - C 6 H 5 N + (CH 3 ) H 2 ). )including.
• carboxylic acid anhydrides include trifluoroacetic anhydride, maleic anhydride, and phthalic anhydride.
• Specific examples of preferred carboxylic acid anhydrides include maleic anhydride.
• sulfonic acids As the acid catalyst in step (ii), sulfonic acids, salts thereof and anhydrides can be used. Therefore, the sulfonic acid may be used as a free acid or as a salt thereof. In addition, the sulfonic acid may be used as its anhydride.
• the sulfonic acids including p- toluenesulfonic acid monohydrate (TsOH ⁇ H 2 O)
• methanesulfonic acid trifluoromethanesulfonic acid (TfOH)
• benzenesulfonic acid p- toluenesulfonic acid
• 10 Contains camphorsulfonic acid.
• sulfonates include pyridinium p-toluenesulfonate (PPTS).
• PPTS pyridinium p-toluenesulfonate
• sulfonic acid anhydrides include anhydrous methanesulfonic acid, anhydrous trifluoromethanesulfonic acid.
• Phosphoric acids can be used as the acid catalyst in the step (ii).
• Phosphoric acids are phosphoric acids and their derivatives. Phosphoric acids are not particularly limited as long as they are chemically acceptable and exhibit the effects of the present invention. Examples of phosphoric acids include, but are not limited to:
• Phosphoric acid may be used as a free acid or as a salt thereof.
• phosphoric acid may be used as its anhydride.
• Examples of phosphoric acid, salts thereof and anhydrides include phosphoric acid (orthophosphoric acid; H 3 PO 4 ), ammonium dihydrogen phosphate, polyphosphoric acid, pyrophosphoric acid (diphosphate) and diphosphorus pentoxide.
• Phosphoric acid monoester may be used as a free acid or as a salt thereof.
• the phosphoric acid monoester may be used as its anhydride as long as it is chemically acceptable.
• Phosphoric acid diesters may be used as free acids or as salts thereof.
• Phosphodiester may be used as its anhydride as long as it is chemically acceptable.
• Luiz acids can be used as the acid catalyst in step (ii).
• Lewis acids include, but are not limited to:
• examples of Lewis acids include, but are not limited to, compounds formed from cations and anions.
• the cation forming the Lewis acid may be used alone or in combination of two or more.
• the anion forming the Lewis acid may be used alone or in combination of two or more.
• the Lewis acid formed from cations and anions may contain components other than cations and anions.
• Examples of cations that form Lewis acid are 1 gene, 2 gene, 3 gene (including lanthanoids), 4 gene, 5 gene, 6 gene, 7 gene, 8 gene, 9 gene, 10 gene on the long periodic table. Includes cations of elements of the genera, 11, 12, 13, 14, and 15.
• Examples of cations of the elements of the 1st to 15th genera on the long periodic table include, but are not limited to: Examples of cations of Group 1 elements include: lithium (Li), sodium (Na), potassium (K) or cesium (Cs) ions. Examples of cations of the two elements include: magnesium (Mg), calcium (Ca) or barium (Ba) ions. Examples of cations of the three elements include: scandium (Sc), yttrium (Y), lanthanum (La), cerium (Ce), samarium (Sm) or ytterbium (Yb) ions. Examples of Group 4 elemental cations include: titanium (Ti), zirconium (Zr) or hafnium (Hf).
• Examples of elemental cations of the genus 5 include: vanadium (V).
• Examples of cations of the 6th element include: Molybdenum ion (Mo) or Tungsten (W) ion.
• Examples of cations of the 7th element include: Manganese (Mn) ions.
• Examples of group 8 elemental cations include: iron ion (Fe) or ruthenium (Ru) ions.
• Examples of cations of the 9th element include: cobalt (Co), rhodium (Rh) or iridium (Ir) ions.
• Examples of cations of the 10th element include: nickel (Ni), palladium (Pd) or platinum (Pt) ions.
• Examples of group 11 elemental cations include: copper (Cu), silver (Ag) or gold (Au) ions.
• elemental cations of Group 12 include: zinc ions.
• Examples of cations for elements of the 13th genus (ie, earth metals) include: ions of boron (B), aluminum (Al), gallium (Ga) or indium (In).
• Examples of carbon group 14 elemental cations include: germanium (Ge) or tin (Sn) ions.
• Examples of cations of the 15 genera include: bismuth ions.
• Preferred examples of cations include, but are not limited to: Magnesium (Mg), Calcium (Ca), Scandium (Sc), Itterbium (Yb), Iron Ion (Fe), Cobalt (Co), Nickel (Ni), Palladium (Pd), Platinum (Pt), Copper (Cu) , Silver (Ag), Gold (Au), Zinc, Boron (B), Aluminum (Al), Iron (Sn) ions.
• Specific examples of the cations of the elements of the 1st to 15th genera on the long periodic table include, but are not limited to: Specific examples of cations of Group 1 elements (ie, alkali metals) include: lithium ion (Li + ), sodium ion (Na + ), potassium ion (K + ) and cesium ion (Cs + ). .. 2 metal selected (i.e., alkaline earth metal) Specific examples of the cation of include the following: magnesium ions (Mg 2 +), calcium ion (Ca 2+) and barium ion (Ba 2+).
• Specific examples of the cations of the elements of the 1st to 15th genera on the long periodic table include, but are not limited to: Specific examples of cations of Group 1 elements (ie, alkali metals) include: lithium ion (Li + ), sodium ion (Na + ), potassium ion (K + ) and cesium ion (Cs + ).
• cations of elements of the three genera include: samarium ion (Sc 3+ ), ytterbium ion (Y 3+ ), lanthanum ion (La 3+ ), cerium (III) ion (Ce). 3+ ), cerium (IV) ion (Ce 4+ ), samarium (II) (Sm 2+ ) ion, samarium (III) (Sm 3+ ) ion and ytterbium (III) (Yb 3+ ).
• cations of the four elements include: titanium (III) ion (Ti 3+ ), titanium (IV) ion (Ti 4+ ), zirconium (IV) ion (Zr 4+ ) and hafnium (IV). ) Ion (Hf 4+ ).
• Specific examples of cations of the 5 elements include: vanadium (II) ion (V 2+ ), vanadium (III) ion (V 3+ ), vanadium (IV) ion (V 4+ ) and vanadium (V).
• Ion (V 5+ ) Ion (V 5+ )
• Specific examples of cations of Group 6 elements include: molybdenum ion (IV) (Mo 4+ ), molybdenum (VI) ion (Mo 6+ ) and tungsten (VI) ion (W 6+ ).
• Specific examples of cations of Group 7 elements include: manganese (II) ion (Mn 2+ ), manganese (IV) ion (Mn 5+ ) and manganese (VII) ion (Mn 7+ ).
• group 8 elemental cations include: Iron ion (II) (Fe 2+ ), iron ion (III) (Fe 3+ ) and ruthenium (III) ion (Ru 3+ ).
• Specific examples of cations of the 9th element include: cobalt (II) ion (Co 2+ ), cobalt (III) ion (Co 3+ ), rhodium (II) ion (Rh 2+ ), rhodium (III). ) Ions (Rh 3+ ) and iridium (III) ions (Ir 3+ ).
• cations of the 10th element include: nickel (II) ion (Ni 2+ ) and palladium (II) ion (Pd 2+ ), platinum (II) ion (Pt 2+ ).
• Specific examples of cations of the 11th element include: copper (I) ion (Cu + ), copper (II) ion (Cu 2+ ), silver (I) ion (Ag + ), gold (I). ) Ion (Au + ) and gold (III) ion (Au 3+ ).
• Specific examples of elemental cations of Group 12 ie, zinc group metals
• elemental cations of the 13th genus include: boron ions (B 3+ ), aluminum ions (Al 3+ ), gallium (III) ions (Ga 3+ ) and indium ions. (III) Ion (In 3+ ).
• Specific examples of cations of the 14th element include: germanium (II) ion (Ge 2+ ), germanium (IV) ion (Ge 4+ ), tin (II) ion (Sn 2+ ) and tin (IV). ) Ion (Sn 4+ ).
• Specific examples of cations of the 15 genera include: bismuth (III) ions (Bi 3+ ).
• Preferred specific examples of cations include the following: magnesium ions (Mg 2 +), calcium ions (Ca 2+), scandium ion (Sc 3+), ytterbium (III) (Yb 3+), iron ion (II) (Fe 2+ ), iron ion (III) (Fe 3+ ), cobalt (II) ion (Co 2+ ), cobalt (III) ion (Co 3+ ), nickel (II) ion (Ni 2+ ), palladium (II) ion (Pd) 2+ ), platinum (II) ion (Pt 2+ ), copper (I) ion (Cu + ), copper (II) ion (Cu 2+ ), silver (I) ion (Ag + ), gold (I) ion (Au) + ), Zinc ion (Zn 2+ ), Boron ion (B 3+ ), Aluminum ion (Al 3+ ), Tin (I
• cations include: calcium ion (Ca 2+ ), Copper (II) ion (Cu 2+ ) and silver (I) ion (Ag + ).
• a cation comprises a transition metal ion.
• the transition metal ion is a cation of an element of the 3rd to 11th groups (including lanthanoids) on the long periodic table. Therefore, examples of transition metal ions include cations of the above 3 to 11 elements (including lanthanoids).
• transition metal ions include, but are not limited to: Scandium (Sc), Ytterbium (Yb), Iron ion (Fe), Cobalt (Co), Nickel (Ni), palladium (Pd), platinum (Pt), Ions of copper (Cu), silver (Ag) and gold (Au).
• transition metal ions include specific examples of cations of the above three genera (including lanthanoids) to 11 elements.
• Preferred specific examples of transition metal ions are Scandium ion (Sc 3+ ), ytterbium (III) (Yb 3+ ), Iron ion (II) (Fe 2+ ), iron ion (III) (Fe 3+ ), Cobalt (II) ion (Co 2+ ), cobalt (III) ion (Co 3+ ), Nickel (II) ion (Ni 2+ ), palladium (II) ion (Pd 2+ ), platinum (II) ion (Pt 2+ ), It contains copper (I) ion (Cu + ), copper (II) ion (Cu 2+ ), silver (I) ion (Ag + ) and gold (I) ion (Au + ). More preferred specific examples of transition metal ions are: It contains copper (II) ions (Cu 2+
• anions that form Lewis acids include, but are not limited to: Halide ions (e.g., fluoride ion (F -), chloride ion (Cl -), bromide ion (Br -), iodide ion (I -)), Sulfate ion (SO 4 2-), nitrate ion (NO 3 -), oxide ions (O 2-), perchlorate ion (ClO 4 -), tetrafluoroborate ion (BF 4 -), hexafluorophosphate acid ion (PF 6 -), hexafluoroantimonate ion (SbF 6 -), Carboxylate ion (e.g., acetate ion (CH 3 CO 2 -; AcO -), trifluoroacetate (CF 3 CO 2 -)) Sulfonate ion (e.g., methanesulfonate ion (CH 3 SO 3
• anions that form Lewis acids include: Fluoride ions (F -), chloride ion (Cl -), bromide ion (Br -), iodide ion (I -)), Trifluoromethanesulfonate ion (CF 3 SO 3 -; TfO -; also referred to as triflate ions), Bis (trifluoromethylsulfonyl) amide ion ((CF 3 SO 2) 2 N -; Tf 2 N -).
• examples of Lewis acids include, but are not limited to, compounds represented by the following formulas; MZn (In the formula, M is 1 gene, 2 gene, 3 gene (including lanthanoid), 4 gene, 5 gene, 6 gene, 7 gene, 8 gene, 9 gene, 10 gene, 11 gene on the long periodic table. , 12, 13, 14 and 15 gene cations. Z is the same or different and is the counter anion of M. n is an integer of 1 to 4. )
• the Lewis acid represented by the above formula may contain components other than Z and M.
• Examples of cations of elements of the 1st to 15th genera on the long periodic table in e-2 are the same as those in e-1 above.
• Preferred examples of cations in e-2 are the same as those in e-1 above.
• Specific examples of the cations of the elements of the 1st to 15th genera on the long periodic table in e-2 are the same as those in e-1 above.
• Preferred specific examples of cations in e-2 are the same as those in e-1 above. More preferred specific examples of cations in e-2 are the same as those in e-1 above.
• e-2 Another preferred example of the cation in e-2 is the same as that in e-1 above, which includes a transition metal ion.
• transition metal ions in e-2 are the same as those in e-1 above.
• Preferred examples of transition metal ions in e-2 are the same as those in e-1 above.
• Specific examples of transition metal ions in e-2, preferable specific examples, and more preferable specific examples are the same as those in e-1 above.
• Z is the same as the example of the anion forming the Lewis acid in e-1 above.
• examples of preferred anions in e-2 are the same as those in e-1 above.
• Examples of more preferred anions in e-2 are the same as those in e-1 above.
• Lewis acids for e-1 and e-2 above include, but are not limited to: Lithium bromide (LiBr), lithium perchlorate (LiClO 4 ), sodium bromide (NaBr), potassium bromide (KBr), scandium bromide (CsBr), magnesium chloride (MgCl 2 ), magnesium bromide (MgBr 2) ), Magnesium trifurate (Mg (OTf) 2 ), Magnesium bis (trifluoromethanesulfonyl) imide (Mg (NTf 2 ) 2 ) Calcium chloride (CaCl 2 ), Calcium bromide (CaBr 2 ) (including hydrate), Calcium triflate (Ca (OTf) 2 ), calcium bis (trifluoromethanesulfonyl) imide (Ca (NTf 2 ) 2 ), scandium chloride (III) (ScCl 3 ), scandium (III) triflate (Sc (OTf) 3 )
• Tetraisopropoxytitanium (IV) (Ti (OPr-i) 4 ) (Tetraisopropoxytitanium (IV) is also called titanium (IV) tetraisopropoxide), Zirconium chloride (I) V) (ZrCl 4 ), Hafnium (IV) Trifurate (Hf (OTf) 4 ), Hafnium (IV) Heptadecafluorooctane Sulfonate (Hf (OSO 2 C 8 F 17 ) 4 ), Vanadium Chloride (III) (VCl 3 ) ), Vanadium oxide (V) (V 2 O 5 ), manganese chloride (II) (MnCl 2 ) (including tetrahydrate, etc.), manganese sulfate (II) (MnSO 4 ) (including pentahydrate, etc.) ), Iron (II) chloride (FeCl 2 ) (including tetrahydrate), Iron (II
• Lewis acids for e-1 and e-2 above include: Magnesium trifurate (Mg (OTf) 2 ), magnesium bis (trifluoromethanesulfonyl) imide (Mg (NTf 2 ) 2 ), calcium trifrate (Ca (OTf) 2 ), calcium bis (trifluoromethanesulfonyl) imide (Ca (NTf 2 )) ) 2 ), Scandium (III) Trifurate (Sc (OTf) 3 ), Titanium Chloride (IV) (TiCl 4 ), Tetramethoxytitanium (IV) (Ti (OMe) 4 ), Tetraisopropoxytitanium (IV) (Ti) (OPr-i) 4 ), iron chloride (III) (FeCl 3 ), iron bromide (III) (FeBr 3 ), iron (III) trifurate (Fe (OTf) 3 ), nickel chloride (II) (NiCl 2 ), magnesium magnesium bis
• Lewis acid for e-1 and e-2 above include: magnesium trifurate (Mg (OTf) 2 ), magnesium bis (trifluoromethanesulfonyl) imide (Mg (NTf 2 ) 2 ). ), Calcium triflate (Ca (OTf) 2 ), Calcium bis (trifluoromethanesulfonyl) imide (Ca (NTf 2 ) 2 ), Scandium (III) triflate (Sc (OTf) 3 ), Copper (II) chloride (CuCl 2 ) ) (Contains dihydrate), copper (II) bromide (CuBr 2 ), copper (II) acetate (Cu (OAc) 2 ), copper (II) trifurate (Cu (OTf) 2 ), bis (trifluo) Rometansulfonyl) imide copper (II) (Cu (NTf 2 ) 2 ), silver chloride (AgCl), silver (I) trifurate (AgOTf).
• Lewis acids for e-1 and e-2 above include: Scandium (III) triflate (Sc (OTf) 3 ), ytterbium (III) triflate (Yb (OTf) 3 ).
• the transition metal triflate will be described. In one embodiment, it is a compound formed from a transition metal ion as a cation and a triflate ion as an anion.
• the transition metal ions are as described above.
• Triflate ions, as described above, trifluoromethanesulfonate ion (CF 3 SO 3 -; TfO -) is.
• the transition metal triflate formed from the transition metal ion and the triflate ion may contain components other than the transition metal ion and the triflate ion.
• the transition metal triflate is a compound represented by the following formula.
• M'Z'm In the formula, M'is a transition metal ion as a cation, Z is a triflate ion as an anion, m is an integer of 1 to 4.
• the transition metal ion is as described above, and the triflate ion is as described above.
• transition metal triflate are appropriate examples of the above specific examples of Lewis acid.
• a preferred specific example of a transition metal triflate is a suitable example of the preferred specific examples of Lewis acid described above.
• a more preferred specific example of a transition metal triflate is a suitable example of the more preferred specific examples of Lewis acid described above.
• a more preferred specific example of a transition metal triflate is a suitable example of the more preferred specific examples of Lewis acid described above.
• examples of Lewis acids include halogens such as iodine, bromine and chlorine.
• halogens such as iodine, bromine and chlorine.
• a more preferred specific example of halogens is iodine.
• Solid acids can be used as acid catalysts.
• solid acids include, but are not limited to, cation exchange resins, heteropolyacids, zeolites, montmorillonite, alumina and the like.
• cation exchange resin is not particularly limited and means a known strong acid or weakly acidic cation exchange resin.
• Specific examples of cation exchange resins include Dow ion (registered trademark) series manufactured by Mitsubishi Chemical Corporation (for example, Diaion SK1B, SK110, SK116, P206, WK40, etc.) and Amberlite manufactured by Rohm and Haas (registered).
• heteropolyacids are 12-molybdo (VI) phosphoric acid n-hydrate; H 3 [PMo 12 O 40 ] and nH 2 O (n ⁇ 30)).
• 12-tungsto (VI) phosphoric acid n-hydrate; H 3 [PW 12 O 40 ], nH 2 O (n ⁇ 30)), 12 tonguesto (VI) Kay Includes, but is not limited to, acid n-hydrate (12-tungsto (VI) silicic acid n-hydrate; H 4 [SiW 12 O 40 ], nH 2 O (n ⁇ 30, for example n ⁇ 26)) and the like. ..
• the 12-molybdic acid n-hydrate is also referred to as phosphomolybdic acid n-hydrate.
• 12 tonguest (VI) phosphate n-hydrate is also referred to as phosphortungstic acid n-hydrate.
• 12 tonguest (VI) silicic acid n-hydrate is also referred to as silicotungstic acid n-hydrate.
• Heteropoly acid salts can also be used as the acid catalyst. Specific examples of heteropolyacid salts include sodium 12-molybdo (VI) phosphate n-hydrate; Na 3 [PMo 12 O 40 ] and nH 2 O (n). ⁇ 30)), etc., but is not limited to this.
• 12 Sodium molybdate (VI) sodium phosphate n-hydrate is also referred to as sodium molybdate n-hydrate.
• zeolites include, but are not limited to, ZSM-5 type, mordenite type, L type, Y type, X type and beta type.
• 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. More preferably, 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 and sulfonic acids.
• preferable specific examples of the acid catalyst are as follows, but are not limited thereto.
• Hydrochloride sulfuric acid, nitrate, trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, maleic acid, maleic anhydride, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 10-campersulfonic acid, phosphoric acid , One or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acid selected from the group consisting of ethyl phosphate, phenyl phosphate, diethyl phosphate and diphenyl phosphate. preferable.
• nitrate Group consisting of nitrate, trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, maleic acid, maleic anhydride, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 10-campersulfonic acid and diphenyl phosphate. More preferably, one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acid selected from the above.
• 1 to 3 acids selected from the group consisting of trifluoroacetic acid, maleic acid and maleic anhydride. More preferably, one or two (preferably one) acids selected from the group consisting of trifluoroacetic acid and maleic acid. Trifluoroacetic acid is more preferred.
• acid catalysts are, but are not limited to: 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 and sulfonic acids are preferred. More preferably, 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 and sulfonic acids.
• the acid catalyst are as follows, but are not limited thereto.
• One or two, more preferably one) acids are preferred.
• One or more selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, maleic acid and p-toluenesulfonic acid (preferably 1 to 3, more preferably 1 or 2, still more preferably 1). Acid is preferred.
• One or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acids selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid are also even more preferred. More preferably, one or two (preferably one) acids selected from the group consisting of trifluoroacetic acid and maleic acid. Trifluoroacetic acid is more preferred.
• preferred examples of acid catalysts are, but are not limited to: Mineral acids However, one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acids selected from the group consisting of carboxylic acids and sulfonic acids, excluding hydrochloric acid, are preferable. Mineral acids However, one or more acids (preferably 1 to 3, more preferably 1 or 2, and even more preferably 1) selected from the group consisting of carboxylic acids and sulfonic acids excluding hydrochloric acid are more preferable. From the same viewpoint as above, preferable specific examples of the acid catalyst are as follows, but are not limited thereto.
• One or two, more preferably one) acids are preferred.
• One or more selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, maleic acid and p-toluenesulfonic acid (preferably 1 to 3, more preferably 1 or 2, still more preferably 1). Acid is preferred.
• One or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acids selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid are also even more preferred. More preferably, one or two (preferably one) acids selected from the group consisting of trifluoroacetic acid and maleic acid. Trifluoroacetic acid is more preferred.
• the acid catalyst may be used alone or in a combination of two or more at any ratio.
• the form of the acid catalyst may be any form as long as the reaction proceeds. Examples of such forms include solids, liquids or gases containing only acid catalysts, aqueous solutions of arbitrary concentrations or solutions of solvents other than water (eg, organic solvents) and the like. The form can be appropriately selected by those skilled in the art.
• the amount of the acid catalyst used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., 0.01 to 1.0 mol, preferably 0.01 to 0.60 mol, more preferably, with respect to 1 mol of the compound of the formula (2). Can exemplify the range of 0.02 to 0.50 mol and 0.05 to 0.40 mol.
• the compound of formula (5) is produced in the presence of an acid-base catalyst.
• the acid-base catalyst is a mixture of acid and base.
• the acid-base catalyst may be any acid-base catalyst as long as the reaction proceeds. In addition, any form may be used as long as the reaction proceeds and is within the scope of the present invention.
• the acid-base catalyst is a salt
• the acid-base catalyst may be a single salt or a double salt.
• the acid-base catalyst may be used in the form of an anhydride.
• the acid-base catalyst may be used in the form of a hydrate.
• the acid and / or base of the acid-base catalyst may be used in the form of a dimer or the like.
• the acid-base catalyst may be used alone or in a combination of two or more at any ratio.
• the form of the acid-base catalyst may be any form as long as the reaction proceeds. Examples of such forms include solids or liquids containing only acid-base catalysts, aqueous solutions of arbitrary concentrations, or solutions of solvents other than water (for example, organic solvents). The form can be appropriately selected by those skilled in the art.
• the acid of the acid-base catalyst the acid exemplified as the acid catalyst can be used.
• preferred examples of the acid-base catalyst acid 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.
• 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 and sulfonic acids are preferred.
• 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 and carboxylic acids are more preferred.
• the acid-base catalyst acid are as follows, but are not limited thereto. Hydrochloride, sulfuric acid, nitrate, trifluoroacetic acid, trichloroacetic acid, dichloroacetic acid, maleic acid, maleic anhydride, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 10-campersulfonic acid, phosphoric acid , One or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acid selected from the group consisting of ethyl phosphate, phenyl phosphate, diethyl phosphate and diphenyl phosphate.
• 1 to 3 (preferably 1 or 2, more preferably 1) acids selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid.
• 1-3 acids preferably 1 or 2, more preferably 1) selected from the group consisting of trifluoroacetic acid, maleic acid and maleic anhydride are also even more preferred.
• Trifluoroacetic acid is more preferred.
• preferred examples of acid-base catalyst acids are, but are not limited to: 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 and sulfonic acids are preferred.
• the acid-base catalyst acid are as follows, but are not limited thereto.
• One or two, more preferably one) acids are preferred.
• One or more selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, maleic acid and p-toluenesulfonic acid (preferably 1 to 3, more preferably 1 or 2, still more preferably 1). Acid is preferred.
• One or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acids selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid are also even more preferred. More preferably, one or two (preferably one) acids selected from the group consisting of trifluoroacetic acid and maleic acid. Trifluoroacetic acid is more preferred.
• acid-base catalyst acids are, but are not limited to: Mineral acids However, one or more (preferably 1 to 3, more preferably 1 or 2, still more preferably 1) acids selected from the group consisting of carboxylic acids and sulfonic acids, excluding hydrochloric acid, are preferable. Mineral acids However, one or more acids (preferably 1 to 3, more preferably 1 or 2, and even more preferably 1) selected from the group consisting of carboxylic acids and sulfonic acids excluding hydrochloric acid are more preferable. From the same viewpoint as above, preferable specific examples of the acid-base catalyst acid are as follows, but are not limited thereto.
• One or two, more preferably one) acids are preferred.
• One or more selected from the group consisting of nitric acid, trifluoroacetic acid, trifluoroacetic anhydride, maleic acid and p-toluenesulfonic acid (preferably 1 to 3, more preferably 1 or 2, still more preferably 1). Acid is preferred.
• One or more (preferably 1-3, more preferably 1 or 2, more preferably 1) acids selected from the group consisting of nitric acid, trifluoroacetic acid and maleic acid are also even more preferred. More preferably, one or two (preferably one) acids selected from the group consisting of trifluoroacetic acid and maleic acid. Trifluoroacetic acid is more preferred.
• amines are preferable.
• R 6 , R 7 and R 8 are independently hydrogen atoms, optionally substituted (C1-C6) alkyl; optionally substituted (C3-C6) cycloalkyl; substituted. which may be (C2-C6) alkenyl; optionally substituted (C2-C6) alkynyl; be, or optionally substituted aryl; or any two of R 6, R 7 and R 8 are Together with the nitrogen atoms to which they are bonded, they form a 4- to 12-membered heterocycle, where the rings formed may be substituted, where R 6 , R 7 and R 8 are. At least one of them is not a hydrogen atom) and may be a primary amine, a secondary amine, a tertiary amine, or a heterocyclic amine.
• the primary amine include, but are not limited to, methylamine, ethylamine, propylamine, butylamine, aniline and the like.
• Specific examples of secondary amines include diethylamine, dipropylamine, diisopropylamine, N-methylaniline (PhNHMe; sometimes abbreviated as N-MeAniline in the present specification), N-ethylaniline, piperidine, and the like. Including, but not limited to, morpholine and the like.
• tertiary amines include 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 include pyridine, 4- (dimethylamino) -pyridine, 4-pyrrolidinopyridine, 2,6-lutidine, quinoline, isoquinoline, 1,8-diazabicyclo [5.4.0].
• DBU -7-Undec-7-ene
• DBN 1,5-diazabicyclo [4.3.0] nona-5-ene
• Nona-5-ene also belongs to tertiary amines.
• 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 its diastereomers, and their analogs. including.
• imidazolinones are expensive, it is industrially preferable not to use imidazolinones.
• acid-base catalyst bases include secondary amines or heterocyclic amines.
• Preferred specific examples of acid-base catalyst bases include N-methylaniline or pyridine.
• the amount of the acid-base catalyst used may be any amount as long as the reaction proceeds.
• the acid-base ratio of the acid-base catalyst may be 1: 1 and may not be 1: 1.
• the amount of the acid used is 0.01 to 1.0 mol, preferably 0.01 to 0, based on 1 mol of the compound of the formula (2) from the viewpoints of yield, suppression of by-products, economic efficiency and the like.
• the range of .60 mol, more preferably 0.02 to 0.50 mol, 0.05 to 0.40 mol can be exemplified.
• the amount of the base used is 0.01 to 1.0 mol, preferably 0.01 to 0, based on 1 mol of the compound of the formula (2) from the viewpoints of yield, suppression of by-products, economic efficiency and the like.
• the range of .60 mol, more preferably 0.02 to 0.50 mol, 0.05 to 0.40 mol can be exemplified.
• the ketone compound can be added in the reaction of step (ii).
• the ketone compound trapped desorbed hydroxy ions and alkoxy ions. Whether or not to use a ketone compound can be appropriately determined by those skilled in the art.
• ketone compounds are acetone, 2-butanone (methyl ethyl ketone), methyl isopropyl ketone, methyl tertiary butyl ketone, 2-pentanone, 3-pentanone, 1-cyclohexanone-1-propanone, 2-hexanone, 3-hexanone, 3 -Heptanone, 4-octanone, 5-nonanonone, acetophenone, 4'-hydroxyacetophenone, benzophenone, cyclopropanone, cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclononanone, cyclodecanone, etc. Not limited to.
• solvent of step (ii) The reaction of step (ii) can be carried out in the presence or absence of a solvent (no solvent). Whether or not a solvent is used in the step (ii) can be appropriately determined by those skilled in the art. When a solvent is used in the reaction of step (ii), any solvent may be used as long as the reaction of step (ii) proceeds. Examples of solvents in step (ii) include water, alcohols (eg, methanol, ethanol, 2-propanol, butanol, etc.), ethers (eg, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, etc.).
• solvents in step (ii) include water, alcohols (eg, methanol, ethanol, 2-propanol, butanol, etc.), ethers (eg, tetrahydrofuran (THF), 1,4-dioxane, diisoprop
• N, N'-dialkylimidazolium salt eg, N-butyl-N'-methylimidazolium salt
• tetraalkylammonium salt eg, tetra-n-butylammonium salt
• N-alkylpyridium salts (eg, n-butylpyridinium salt), tetraalkylphosphonium salts (eg, trishexyl (tetradecyl) phosphonium salt) are mentioned, and examples of these salts are tetrafluoroborate, acetate, tetrachloroaluminate. Includes, but is not limited to, acid salts, hexafluorophosphates, chlorides, tosilates, trifluoromethanesulfonates) and any combination thereof in any proportion.
• ionic liquid examples include 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BMIMCF 3 ), 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-.
• BMIMCF 3 1-butyl-3-methylimidazolium trifluoromethanesulfonate
• 1-ethyl-3-methylimidazolium chloride 1-ethyl-3-methylimidazolium bromide
• Ethyl-3-methylimidazolium chloride 1-ethyl-3-methylimidazolium iodide, 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, 1-ethyl -3-Methylimidazolium dicyanamide, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylimidazolium bis (trifluoromethanesulfonyl) imide, 1-ethyl-3-methylimidazolium thiocyanate , 1-Ethyl-3-methylimidazolium methanesulfonate, 1-ethyl-3-methylimidazolium diethyl phosphate, 1-ethyl-3-methylimidazolium hexafluorophosphate, 1-ethyl-3-methylimidazolium tetra Ch
• the step (ii) is preferably solvent-free.
• preferred examples of the solvent in step (ii) include water, ketones, nitriles, halogenated aliphatic hydrocarbons, aromatic hydrocarbon derivatives and any combination thereof in any proportion. ..
• Preferred specific examples of the solvent in step (ii) include water, acetone, acetonitrile, dichloromethane, toluene and any combination thereof in any proportion.
• the amount of the solvent used in the reaction of step (ii) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, economic efficiency and the like, the range of 0 (zero) to 10 L (liter), preferably 0.1 to 5 L, can be exemplified with respect to 1 mol of the compound of the formula (3). When a combination of two or more solvents is used, 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 may be separated into two layers as long as the reaction proceeds.
• step (i) and step (ii) are performed without isolating the compound of formula (3)
• the amount of the solvent or the like in step (ii) is set by the ratio with the compound of formula (2). can do.
• the amount of the solvent used in the step (ii) can be exemplified in the range of 0 (zero) to 10 L (liter), preferably 0.1 to 5 L, with respect to 1 mol of the compound of the formula (2).
• reaction temperature of step (ii) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency and the like, -30 ° C. (-30 ° C.) to 160 ° C., preferably ⁇ 10 ° C. to 120 ° C., more preferably 0 to 100 ° C. can be exemplified.
• reaction time of step (ii) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency and the like, the range of 0.5 hours to 72 hours, preferably 1 hour to 60 hours, and more preferably 1 hour to 48 hours can be exemplified.
• step (ii); compound of formula (5) The product of step (ii) is a compound of formula (5) corresponding to the compound of formula (3) used as a raw 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-dihydroisoxazole
• Steps (i) and (ii) may be performed in a "stepwise procedure” as shown in Examples 15-29, or “bulk preparation” as shown in Examples 59 and 60. (Addition at once) ”may be used. Both of these cases fall within the scope of the invention. That is, both of these cases are included in the range of [I-1], [II-1] and [III-1].
• the step (pre-i) is a step of preparing the compound of the formula (2).
• the reaction of step (pre-i) is oxidation.
• the step (pre-i) is a step of reacting the compound of the formula (1) with sodium hypochlorite to produce the compound of the formula (2).
• the compound of the formula (1) is used as a raw material for the step (pre-i).
• the compound of the formula (1) is a known compound, or can be produced from a known compound according to a known method. Specific examples of the compound of formula (1) include, but are not limited to, 3-methyl-1,3-butanediol (3-methylbutane-1,3-diol, 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-methyl-3-phenoxybutanol, 3- (benzyloxy) -3-methylbutanol, 3-methyl-1 , 3-Pentanediol, 3-Ethyl-1,3-Pentanediol, 3,4-dimethyl-1,3-Pentanediol, 3,4,4-trimethyl-1,3-Pentanediol, 4-Chloro-3 -Methyl-1,3-butanediol, 4,4,4-trifluoro-3-methyl-1,3-butanediol, 1- (2-hydroxyethyl) cyclopropan
• the oxidizing agent used in the step (pre-i) may be any oxidizing agent as long as the reaction proceeds.
• the oxidizing agent includes a bromine-based oxidizing agent.
• Preferred examples of the bromine-based oxidizing agent include bromine (liquid bromine), bromine chloride, bromate, bromate, hypobromous acid and the like.
• a chlorine-based oxidant can be mentioned.
• Preferred examples of chlorine-based oxidizing agents are chlorine gas, chlorine dioxide, hypochlorous acid or a salt thereof (for example, sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, barium hypochlorite, etc.).
• Hypochlorous acid or salts thereof eg sodium chlorite, potassium chlorite, barium chlorite, nickel chlorite, etc.
• hypochlorous acid or salts thereof eg ammonium chlorite, sodium chlorite, chlorite More preferable examples such as potassium, calcium chlorite, barium chlorate, etc.
• chlorinated isocyanuric acid or a salt thereof for example, dichloroisosianulic acid, sodium dichloroisosianulate, potassium dichloroisosianulate, trichloroisosianulic acid, etc.
• Oxidizing agents may be used alone or in any combination of two or more at any ratio.
• the form of hypochlorite as the oxidizing agent in the step (pre-i) may be any form as long as the reaction proceeds, and examples of the form are hypochlorite hydrate (solid) or liquid. , Or a solution of an aqueous solution of an arbitrary concentration or a solution of a solvent other than water (for example, an organic solvent), and can be appropriately selected by those skilled in the art. From the viewpoint of ease of handling, economic efficiency and the like, a preferable example includes an aqueous solution of hypochlorite.
• the concentration of the aqueous solution of hypochlorite as the oxidizing agent in the step (pre-i) is 1% or more and less than 40%, preferably 3% or more and 15% or less in consideration of economic efficiency. Contains aqueous solution.
• the amount of hypochlorite used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., 0.5 to 2 mol, preferably 0.9 to 1.5 mol, more preferably 1. The range of 0 to 1.2 mol can be exemplified.
• nitroxyl radical catalyst in step (pre-i) The reaction of step (pre-i) is carried out in the presence of a nitroxyl radical catalyst.
• a nitroxyl radical catalyst As the nitroxyl radical catalyst in the step (pre-i), a conventionally known nitroxyl radical compound can be used.
• nitroxyl radical compounds are TEMPO-based catalysts (eg, 2,2,6,6-tetramethylpiperidin 1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl).
• the amount of the nitroxyl radical catalyst used in the step (pre-i) is usually 0.0001 mol to 0.3 mol, preferably 0.001 mol, based on 1 mol of the compound (nitroso compound) of the formula (1).
• the range from mol to 0.1 mol can be exemplified.
• phase transfer catalyst in step (pre-i) When the reaction of step (pre-i) is carried out in a mixed solvent of water and another organic solvent, it may be carried out in the presence or absence of a phase transfer catalyst. Whether or not to use a phase transfer catalyst can be appropriately determined by those skilled in the art.
• the phase transfer catalyst include quaternary ammonium salts (eg, tetrabutylammonium bromide, tetrabutylammonium hydrogen sulfate, trimethylbenzylammonium chloride, etc.) and quaternary phosphonium salts (eg, tetrabutylphosphonium bromide, tetraoctylphosphonium bromide). , Tetraphenylphosphonium bromide, etc.), crown ethers (eg, 12-crown-4, 15-crown-5, 18-crown-6, etc.), but are not limited thereto.
• quaternary ammonium salts eg,
• the phase transfer catalyst is preferably a quaternary ammonium salt or a quaternary phosphonium salt, and more preferably a quaternary ammonium salt.
• interphase transfer catalyst in the step (pre-i) are preferably tetramethylammonium chloride, tetramethylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydroxide.
• Chloride trimethylbenzylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide
• examples thereof include mid, benzyllauryldimethylammonium chloride, benzyldimethyloctadecylammonium chloride, benzyldimethyloctadecylammonium bromide, and myristyltrimethylammonium bromide.
• the amount of the phase transfer catalyst used in the step (pre-i) is usually 0.001 mol to 0.5 mol, preferably 0.005 mol to 0.3, based on 1 mol of the compound of the formula (1). It is a mole.
• Copper catalyst in step (pre-i) The reaction of step (pre-i) can be carried out in the presence or absence of a copper catalyst. Whether or not to use a copper catalyst can be appropriately determined by those skilled in the art. Examples of copper catalysts include copper halide (eg, copper (I) chloride, copper (II) chloride, copper (I) bromide, copper (II) bromide, copper (I) iodide, etc.), copper acetate.
• copper halide eg, copper (I) chloride, copper (II) chloride, copper (I) bromide, copper (II) bromide, copper (I) iodide, etc.
• the reaction of the step (pre-i) is preferably carried out in the range of pH 3 to 9, and can be carried out in the presence or absence of a buffer that adjusts the pH.
• a buffer can be appropriately decided by those skilled in the art.
• Examples of buffers are carbonates (eg sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), phosphoric acids (eg phosphoric acid, trisodium phosphate, tripotassium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate) , Sodium dihydrogen phosphate, potassium dihydrogen phosphate, etc.), acetic acids (for example, acetic acid, sodium acetate, etc.) can be exemplified, and only one of them can be used alone, or two or more. It can also be used as a mixture, but is not limited to these.
• the reaction in step (pre-i) is preferably carried out in the presence of a solvent.
• the solvent of the step (pre-i) may be any solvent as long as the reaction of the step (pre-i) proceeds.
• solvents for step (pre-i) are water, ethers (eg, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl.
• carboxylic acid esters eg ethyl acetate, butyl acetate, etc.
• aromatic hydrocarbon derivatives eg, benzene, toluene, xylene, chlorobenzene, etc.
• halogenated aliphatic hydrocarbons eg, dichloromethane, etc.
• Chloro, 1,2-dichloroethane (EDC), etc. any combination thereof in any proportion, but not limited to these.
• preferred examples of the solvent in step (pre-i) are water, ethers, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons and any of them in any proportion. Including combinations of.
• Preferred specific examples of the solvent for step (pre-i) include water, diisopropyl ether, tetrahydrofuran (THF), dichloromethane, toluene and any combination thereof in any proportion.
• the amount of the solvent used in the step (pre-i) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, economic efficiency and the like, the range of 0 (zero) to 10 L (liter), preferably 0.1 to 5 L, can be exemplified with respect to 1 mol of the compound of the formula (1). When a combination of two or more solvents is used, the proportion of the two or more solvents may be any ratio as long as the reaction proceeds.
• the solvent may be a single layer or may be separated into two layers as long as the reaction proceeds.
• the solvent of the step (ii) or the like may be used.
• the amount can be set by the ratio with the compound of the formula (1).
• the amount of the solvent used in the step (ii) can be exemplified in the range of 0 (zero) to 10 L (liter), preferably 0.1 to 5 L, with respect to 1 mol of the compound of the formula (1).
• reaction temperature of step (pre-i) The reaction temperature of the step (pre-i) is not particularly limited. From the viewpoint of yield, suppression of by-products, economic efficiency, etc., the temperature is -10 ° C (-10 ° C) to 100 ° C, preferably in the range of -10 ° C to 80 ° C, more preferably (-10 ° C to 40 ° C). It can be illustrated.
• reaction time of step (pre-i) The reaction time of the step (pre-i) is not particularly limited. From the viewpoint of yield, by-product suppression, economic efficiency and the like, the range of 0.1 hour to 48 hours, preferably 0.1 hour to 24 hours, and more preferably 0.5 hour to 12 hours can be exemplified.
• the compound of formula (2) which is a product of step (pre-i), can be used as a raw material for step (i).
• the compound (2) obtained in the step (pre-i) may be isolated and used as a raw material for the step (i), or may be isolated and used as a raw material for the step (i).
• the solvent used in the step (pre-i) may be used as the solvent in the step (i).
• the compound of formula (3) which is a product of step (i), can be used as a raw material for step (ii).
• the compound of (3) obtained in step (i) may be isolated and used as a raw material for step (ii), or may be used as a raw material for step (ii) without being isolated.
• the solvent used in the step (i) may be used as the solvent in the step (ii).
• the room temperature is 10 ° C to 35 ° C.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the aqueous layer was extracted 3 times with dichloromethane (240.05 ml, 0.5 L / mol) and all the organic layers were combined.
• Dichloromethane was distilled off under reduced pressure until the amount of dichloromethane with respect to 3-hydroxy-3-methylbutanal (2-a) became 0.5 L / mol, and the desired product was obtained as a dichloromethane solution.
• the dichloromethane solution was analyzed from the calibration curve by the GC internal standard method to determine the yield. 3-Hydroxy-3-methylbutanal: 84.6%.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the aqueous layer was extracted twice with dichloromethane (144.02 ml, 0.5 L / mol) and all organic layers were combined.
• Dichloromethane was distilled off under reduced pressure until the amount of dichloromethane with respect to 3-hydroxy-3-methylbutanal (2-a) became 0.5 L / mol, and a solution of the target dichloromethane (206.52 g, 0.5 L / mol) was prepared. (Containing dichloromethane) was obtained.
• the dichloromethane solution was analyzed from the calibration curve by the GC internal standard method to determine the yield. 3-Hydroxy-3-methylbutanal: 79.5%.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the organic layer and the aqueous layer were analyzed from the calibration curve by the GC internal standard method to determine the yield.
• 3-Hydroxy-3-methylbutanal 75.1%.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the organic layer and the aqueous layer were analyzed from the calibration curve by the GC internal standard method to determine the yield.
• 3-Hydroxy-3-methylbutanal 76.4%.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the organic layer and the aqueous layer were analyzed from the calibration curve by the GC internal standard method to determine the yield.
• 3-Hydroxy-3-methylbutanal 74.8%.
• GCArea% is also referred to as the area percentage of GC.
• Cu (OTf) 2 Copper trifluoromethanesulfonate
• Example 14 When 3-methoxy-3-methylbutanal (2-b) is used as a raw material in Examples described later, a dichloromethane solution of 2-b obtained in the same manner as in Example 14 is used, or Example 14 The crude 2-b obtained by distilling dichloromethane from the dichloromethane solution of 2-b obtained in the same manner as above was used.
• Step (pre-i) (oxidation) After dissolving 3-methoxy-3-methylbutanol (10.00 g, 84.62 mmol, 100 mol%) in dichloromethane (84.62 ml, 1.0 L / mol) in a 200 mL four-necked flask, tetrabutylammonium bromide (0.27 g, 0.85 mmol, 1 mol%), 2,2,6,6-tetramethylpiperidin 1-oxyl free radical (0.013 g, 0.084 mmol, 0.1 mol%), phosphoric acid (0.98 g) , 8.46 mmol, 10 mol%) was added.
• aqueous sodium hypochlorite solution (13.29 wt%, 52.14 g, 93.08 mmol, 110 mol%) was added dropwise over a range of 0 to 10 ° C. over 4 hours, followed by stirring for 1 hour.
• the target components excluding the solvent etc. in the reaction mixture were as follows; 3-Methoxy-3-methylbutanal: 90.2%.
• a 1.0 mol / L sodium thiosulfate aqueous solution (7.35 g, 6.35 mmol, 7.5 mol%) was added, and the mixture was stirred for 30 minutes.
• Step (i) (Oximelation) Hydroxylamine sulfate (6.94 g, 42.31 mmol, 100 mol% (converted as hydroxylamine (NH 2 OH)) was added to the mixture obtained in the above step (pre-i), and the temperature was within the range of 10 to 20 ° C. After dropping a 48% aqueous sodium hydroxide solution (7.05 g, 84.62 mmol, 100 mol%), the mixture was stirred at the same temperature for 1 hour. As a result of GC analysis (area percentage) of the reaction mixture, the target components excluding the solvent etc. in the reaction mixture were as follows; 3-Methoxy-3-methylbutanal oxime: 89.6%.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the aqueous layer was re-extracted with dichloromethane (42.31 ml, 0.5 L / mol) and all organic layers were combined.
• Dichloromethane in the organic layer was distilled off under reduced pressure to obtain 12.13 g of crude 3-b.
• the yield was determined by analyzing the crude product obtained from the calibration curve by the GC internal standard method.
• 3-Methoxy-3-methylbutanal oxime 86.9%.
• steps (pre-i) and step (i) were carried out in the same manner as in Example 15 except that the amount of sodium hypochlorite and the addition of the copper catalyst were changed as shown in the table.
• the results of Examples 15-18 are shown in the table.
• a 200 ml separable flask was charged with crude 2-a (72.76 g, 81.23 mmol, 100 mol%), dissolved in water (48.01 ml, 0.6 L / mol), and then hydroxylamine sulfate (7.88 g). , 96.02 mmol, 118 mol% (converted as hydroxylamine (NH 2 OH))) was added.
• a 48% aqueous sodium hydroxide solution (8.00 g, 96.02 mmol, 118 mol%) was added dropwise in the range of 15 to 25 ° C., and the mixture was stirred for 30 minutes.
• step (i) and step (ii) were carried out in the same manner as in Example 21 except that the catalyst, solvent and time were changed as shown in the table.
• the results of Examples 21 to 24 are shown in the table.
• TFA Trifluoroacetic acid p-TsOH ⁇ H 2 O: Paratoluenesulfonic acid monohydrate
• Trifluoroacetic acid (0.29 g, 2.53 mmol, 35 mol%) and N-methylaniline (0.09 g, 0.87 mmol, 12 mol%) were added, and the mixture was 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: 79.6%.
• step (i) and step (ii) were carried out in the same manner as in Example 26, except that the addition of the oxime agent and the neutralizing agent was changed.
• the results of Examples 26-29 are shown in the table.
• Example No. 33 used Pyridinium p-Toluenesulfonate (TCI product code; P0942) in the reaction, but described p-TsOH and Pyridine as acid and base catalysts, respectively.
• DBSA Dodecylbenzene Sulfonic Acid Sc (OTf) 3 : Scandium Triflate (III) Yb (OTf) 3 : Ytterbium triflate (III)
• TFA antide Trifluoroacetic anhydride BMIMCF 3 : 1-Butyl-3-methylimidazolium trifluoromethanesulfonate
• Example 56 The reaction and analysis were carried out in the same manner as in Example 56, except that the solid acid catalyst, the solvent and the aging time were changed.
• the results of Examples 56-58 are shown in the table.
• the obtained mixture was divided into an organic layer and an aqueous layer, and the organic layer and the aqueous layer were separated.
• the aqueous layer was extracted 3 times with dichloromethane (240.05 ml, 0.5 L / mol) and all the organic layers were combined.
• Dichloromethane was distilled off under reduced pressure until the amount of dichloromethane with respect to 2-a became 0.5 L / mol to obtain a dichloromethane solution of 2-a (357.51 g, containing 0.5 L / mol of dichloromethane).
• the dichloromethane solution obtained from the calibration curve by the GC internal standard method was analyzed to determine the yield.
• 3-Hydroxy-3-methylbutanal 63.6%.
• the present invention provides a novel method for producing a compound of the formula (5), which is useful as an intermediate for producing pharmaceuticals and agricultural chemicals.
• the manufacturing method of the present invention is economical, environmentally friendly, and has high industrial utility value. Therefore, the present invention has high industrial applicability.

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