WO2009116577A1 - Processes for production of 1-(substituted phenyl)-1- substituted silyl ethers, alcohols or ketones, and intermediates - Google Patents

Processes for production of 1-(substituted phenyl)-1- substituted silyl ethers, alcohols or ketones, and intermediates Download PDF

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WO2009116577A1
WO2009116577A1 PCT/JP2009/055309 JP2009055309W WO2009116577A1 WO 2009116577 A1 WO2009116577 A1 WO 2009116577A1 JP 2009055309 W JP2009055309 W JP 2009055309W WO 2009116577 A1 WO2009116577 A1 WO 2009116577A1
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group
formula
compound represented
substituted
haloalkyl
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PCT/JP2009/055309
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Japanese (ja)
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一隆 的場
学 八尾坂
紘久 齋藤
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日産化学工業株式会社
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C07F7/1872—Preparation; Treatments not provided for in C07F7/20
    • C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/52—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition by dehydration and rearrangement involving two hydroxy groups in the same molecule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present invention relates to a process for producing aromatic ketone compounds, substituted silyl ether compounds and 1- (substituted phenyl) -1-substituted alcohol compounds useful as intermediates for the production of functional materials such as medical and agricultural chemicals or electronic materials, and 1
  • the present invention relates to a-(substituted phenyl) -2,2,2-trifluoroethanol compound and a substituted trimethylsilyl ether compound.
  • Patent Document 2 and Non-Patent Documents 9 to 12 using a fluorine compound as a catalyst have been conventionally known, they are not necessarily suitable for industrialization.
  • an organic base such as triethylamine is used, but if the amount used is a catalyst amount, the yield is low, which is not satisfactory as an industrial production method.
  • Non-patent documents 1 to 7 all use materials and heavy metals that are difficult to obtain in large quantities, leading to an increase in manufacturing costs and waste, which is not satisfactory as an industrial production method.
  • Non-Patent Document 8 also describes a method using a relatively inexpensive catalyst, but it is not satisfactory as an industrial production method because it requires a solvent that is difficult to recover.
  • Patent Document 3 is not suitable for industrial production because a compound having a strong odor is by-produced after the reaction.
  • Patent Document 4 is not satisfactory as an industrial production method because the yield of the product is not high.
  • the methods described in Patent Documents 13 to 17 use materials and heavy metals that are difficult to obtain in large quantities, leading to an increase in manufacturing costs and waste, and are not satisfactory as an industrial production method.
  • a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound is produced using an aromatic aldehyde compound as a starting material without using expensive reagents or heavy metals.
  • the method is unknown and leaves room for improvement.
  • Patent Document 5 shows only an example in which 2,2,2-trifluoro-1- (4-nitrophenyl) ethanone was synthesized from methyl 4-nitrobenzoate, and the yield was about 47%. It was difficult to generalize as an industrial production method.
  • the reaction is carried out at a relatively high temperature in a dimethoxyethane solvent as described in Patent Documents 6 and 7, trifluoromethyltrimethylsilane is considered to be produced by further reaction of the target trifluoroacetophenone with trifluoromethyltrimethylsilane. There was a problem that the yield of the target product was lowered because a relatively large amount of by-product containing two groups was produced.
  • Non-Patent Documents 18 and 20 the reaction must be performed at an extremely low temperature of ⁇ 78 ° C., which is not satisfactory as an industrial production method.
  • a by-product is produced by further reacting the target carbonyl compound depending on the substrate, so it may be difficult to obtain the target carbonyl compound with high selectivity and high yield. It was.
  • the method described in Non-Patent Document 9 uses cesium fluoride as a catalyst. However, the reaction does not proceed in a low-polar solvent commonly used in industry such as toluene, and the reaction substrate is used without a solvent. Since the risk of runaway reaction of adding cesium fluoride as a catalyst to the mixture as a solid is extremely high, it was not satisfactory as an industrial production method.
  • a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted carbonyl compound using a benzoate ester compound as a starting material is used in a low-cost industrially typical process represented by toluene.
  • a method for producing a high yield and high selectivity in a polar solvent is not known except that the reaction is carried out at an extremely low temperature of ⁇ 78 ° C., leaving room for improvement.
  • the present inventors have represented a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound as a starting material by using an aromatic aldehyde compound as a starting material.
  • a low-polarity solvent in the presence or absence of a water-soluble solvent, the reaction was carried out using an easily available material such as potassium carbonate as a catalyst, and a method for producing in high yield was found, leading to the invention. It was.
  • a reaction was carried out using an oxidant to find a method for producing in a high yield, leading to the invention.
  • a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted carbonyl compound using a benzoic acid ester compound as a starting material is subjected to a catalyst at a temperature higher than ⁇ 50 ° C. in a low polarity solvent typified by toluene.
  • the present invention has been carried out to find a method of producing a product with high selectivity and high yield, leading to the invention.
  • R 1 represents C 1 -C 6 haloalkyl or C 3 -C 8 halocycloalkyl
  • X is a halogen atom, cyano, nitro, —SF 5 , C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, cyano (C 1 -C 6 ) Alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkenyl, hydroxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 ,
  • R 6 is C 1 -C 6 alkyl, —CHO, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C Represents 6 alkoxythiocarbonyl, C 1 -C 6 alkyldithiocarbonyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl, R 7 represents a hydrogen atom or C 1 -C 6 alkyl, m represents an integer of 0 to 5, r represents an integer of 0-2.
  • a compound represented by formula (2) by reacting a 1- (substituted phenyl) -1-substituted alcohol compound represented by the following formula with an oxidizing agent in the presence of an oxidation catalyst and an additive: [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of the aromatic ketone compound represented by this.
  • X is a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1- C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 , —NH 2 or —N (R 7 ) R 6 and when m represents 2 or more, each X may be the same as or different from each other,
  • R 6 represents C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, or C 1 -
  • an aromatic ketone compound, a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound useful for the synthesis of a production intermediate of a functional material such as a medical pesticide or an electronic material Starting from 1- (substituted phenyl) -1-substituted alcohol compounds, aromatic aldehyde compounds, substituted silicon compounds or substituted silyl ether compounds, and benzoic acid ester compounds, reagents such as catalysts are appropriately selected, and industries such as toluene In a solvent that is easy to use, it can be produced with high yield and high selectivity while suppressing the formation of a by-product containing two trifluoromethyl groups, which is useful for industrial production. Can provide a method.
  • the compound represented by the general formula (1), (3), (6) to (11) or (13) described in the present application has an optically active substance resulting from the presence of one or more asymmetric carbon atoms.
  • the compounds described herein include all optically active forms or racemates.
  • hydrohalic acid salts such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid, nitric acid
  • Inorganic acid salts such as sulfuric acid, phosphoric acid, chloric acid, perchloric acid, sulfonic acid salts such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid , Salt of carboxylic acid such as propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, citric acid or glutamic acid
  • those which can be converted into a metal salt according to a conventional method include, for example, alkali metal salts such as lithium, sodium and potassium, alkaline earth metal salts such as calcium, barium and magnesium, or aluminum
  • alkali metal salts such as lithium, sodium and potassium
  • alkaline earth metal salts such as calcium, barium and magnesium
  • aluminum the salt of
  • those that can be converted into an amine salt according to a conventional method are, for example, ammonia, methylamine, ethylamine, propylamine, butylamine, pentylamine, benzylamine, aniline, dimethylamine, diethylamine,
  • the salt may be a salt of dipropylamine, dibutylamine, dipentylamine, pyrrolidine, piperidine, piperazine, morpholine, dibenzylamine, trimethylamine, triethylamine, tripropylamine, tributylamine, tripentylamine, tribenzylamine and the like.
  • n- represents normal
  • i- represents iso
  • s- represents secondary
  • t- represents tertiary
  • Ph represents phenyl
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • the notation “halo” also represents these halogen atoms.
  • C a -C b alkyl represents a linear or branched hydrocarbon group having a carbon number of a to b, such as a methyl group, an ethyl group, an n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 1,1-dimethylbutyl group, Specific examples include 1,3-dimethylbutyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group,
  • C a -C b cycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms, and forms a monocyclic or complex ring structure having 3 to 6 members. I can do it. Each ring may be optionally substituted with an alkyl group within the range of the specified number of carbon atoms.
  • cyclopropyl group 1-methylcyclopropyl group, 2-methylcyclopropyl group, 2,2-dimethylcyclopropyl group, 2,2,3,3-tetramethylcyclopropyl group, cyclobutyl group, cyclopentyl group, 2- Specific examples include methylcyclopentyl group, 3-methylcyclopentyl group, cyclohexyl group, 2-methylcyclohexyl group, 3-methylcyclohexyl group, 4-methylcyclohexyl group, bicyclo [2.2.1] heptan-2-yl group, and the like. Each of which is selected for each specified number of carbon atoms.
  • aromatic group in the present specification examples include a phenyl group, a naphthyl group, an anthryl group, and the like.
  • C a -C b haloalkyl in the present specification is a linear or branched chain consisting of a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom.
  • fluoromethyl group chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl Group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl Group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group, 2,2-dichloro-2 -Fl group, 2-chloro-2,2-
  • cyano (C a -C b ) alkyl in the present specification is a straight or branched chain consisting of a to b carbon atoms, in which a hydrogen atom bonded to a carbon atom is optionally substituted with a cyano group
  • C a -C b halocycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. And can form monocyclic or complex ring structures from 3 to 6-membered rings.
  • Each ring may be optionally substituted with an alkyl group within the range of the specified number of carbon atoms, and the substitution with a halogen atom may be a ring structure part, a side chain part, They may be both, and when they are substituted by two or more halogen atoms, the halogen atoms may be the same as or different from each other.
  • 2,2-difluorocyclopropyl group, 2,2-dichlorocyclopropyl group, 2,2-dibromocyclopropyl group, 2,2-difluoro-1-methylcyclopropyl group, 2,2-dichloro-1-methyl Cyclopropyl group, 2,2-dibromo-1-methylcyclopropyl group, 2,2,3,3-tetrafluorocyclobutyl group, 2- (trifluoromethyl) cyclohexyl group, 3- (trifluoromethyl) cyclohexyl group , 4- (trifluoromethyl) cyclohexyl group and the like are listed as specific examples, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkenyl is a linear or branched chain composed of a to b carbon atoms and has one or more double bonds in the molecule.
  • C a -C b haloalkenyl is a linear or branched chain having a carbon number of a to b, wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. And an unsaturated hydrocarbon group having one or more double bonds in the molecule.
  • the halogen atoms may be the same as or different from each other.
  • C a -C b alkynyl represents a linear or branched chain having a carbon number of a to b and an unsaturated group having one or more triple bonds in the molecule.
  • Specific examples include a 1-dimethyl-2-propynyl group, a 2-hexynyl group, and the like, and each is selected within the specified number of carbon atoms.
  • C a -C b alkoxy in the present specification represents an alkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, a methoxy group, an ethoxy group, an n-propyloxy group, Specific examples include i-propyloxy group, n-butyloxy group, i-butyloxy group, s-butyloxy group, t-butyloxy group, n-pentyloxy group, n-hexyloxy group and the like. It is selected in the range of the number of atoms.
  • C a -C b haloalkoxy in the present specification represents a haloalkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethoxy group, trifluoromethoxy group, chlorodifluoro Methoxy group, bromodifluoromethoxy group, 2-fluoroethoxy group, 2-chloroethoxy group, 2,2,2-trifluoroethoxy group, 1,1,2,2, -tetrafluoroethoxy group, 2-chloro-1 , 1,2-trifluoroethoxy group, 2-bromo-1,1,2-trifluoroethoxy group, pentafluoroethoxy group, 2,2-dichloro-1,1,2-trifluoroethoxy group, 2,2 , 2-trichloro-1,1-difluoroethoxy group, 2-bromo-1,1,2,2-tetrafluoroethoxy group, 2,2,
  • C a -C b alkylsulfonyl in the present specification represents an alkyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylsulfonyl group, ethylsulfonyl group, n- Specific examples include propylsulfonyl group, i-propylsulfonyl group, n-butylsulfonyl group, i-butylsulfonyl group, s-butylsulfonyl group, t-butylsulfonyl group, n-pentylsulfonyl group, n-hexylsulfonyl group and the like. Each of which is selected for each specified number of carbon atoms.
  • C a -C b haloalkylsulfonyl in the present specification represents a haloalkyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethylsulfonyl group, trifluoromethylsulfonyl group Chlorodifluoromethylsulfonyl group, bromodifluoromethylsulfonyl group, 2,2,2-trifluoroethylsulfonyl group, 1,1,2,2-tetrafluoroethylsulfonyl group, 2-chloro-1,1,2-trimethyl Specific examples include a fluoroethylsulfonyl group, a 2-bromo-1,1,2,2-tetrafluoroethylsulfonyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkylcarbonyl in the present specification represents an alkyl-C (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group.
  • alkyl-C (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group.
  • Specific examples thereof include isobutyryl group, valeryl group, isovaleryl group, 2-methylbutanoyl group, pivaloyl group, hexanoyl group, heptanoyl group and the like, and each is selected in the range of the designated number of carbon atoms.
  • C a -C b haloalkylcarbonyl in the present specification represents a haloalkyl-C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, such as a fluoroacetyl group, a chloroacetyl group, Difluoroacetyl group, dichloroacetyl group, trifluoroacetyl group, chlorodifluoroacetyl group, bromodifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, heptafluorobutanoyl group, 3-chloro-2,2-dimethylpropanoyl group Etc. are given as specific examples, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkoxycarbonyl represents an alkyl-O—C (O) — group having the above-mentioned meanings consisting of a to b carbon atoms, for example, methoxycarbonyl group, ethoxycarbonyl Specific examples include a group, n-propyloxycarbonyl group, i-propyloxycarbonyl group, n-butoxycarbonyl group, i-butoxycarbonyl group, t-butoxycarbonyl group, etc. Selected.
  • C a -C b alkylthiocarbonyl represents an alkyl-S—C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (O) -Group, ethylthio-C (O)-group, n-propylthio-C (O)-group, i-propylthio-C (O)-group, n-butylthio-C (O)-group, i-butylthio-C Specific examples include (O) -group, t-butylthio-C (O) -group, etc., and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkoxythiocarbonyl represents an alkyl-O—C (S) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methoxy-C (S ) -Group, ethoxy-C (S) -group, n-propyloxy-C (S) -group, i-propyloxy-C (S) -group, etc. Selected in a range of numbers.
  • C a -C b alkyldithiocarbonyl represents an alkyl-S—C (S) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (S ) -Group, ethylthio-C (S) -group, n-propylthio-C (S) -group, i-propylthio-C (S) -group and the like. Selected by range.
  • alkoxy (C d -C e ) haloalkyl represents a hydrogen atom or halogen bonded to a carbon atom by any C a -C b alkoxy group, C a -C b haloalkoxy group or hydroxyl group, respectively, as defined above.
  • the substituent represented by X is preferably a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl,- OH, —OR 5 , —NH 2 and —N (R 7 ) R 6 , more preferably fluorine atom, chlorine atom, bromine atom, iodine atom, cyano, methyl, trifluoromethyl, pentafluoroethyl, tri Fluoromethoxy, difluoromethoxy, bromodifluo
  • m representing the number of substituents represented by X preferably includes 1, 2 and 3.
  • the position of the substituent represented by X preferably includes a meta position and a para position with respect to the bonding position with the carbon to which R 1 is bonded.
  • the substituent represented by R 1 preferably includes C 1 -C 4 haloalkyl, more preferably difluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and trifluoromethyl. Very particular preference is given to chlorodifluoromethyl and trifluoromethyl.
  • the substituent represented by R 2 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
  • the substituent represented by R 3 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
  • the substituent represented by R 4 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
  • the substituent represented by R 5 preferably includes C 1 -C 6 haloalkyl and C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, more preferably trifluoro Examples thereof include methyl and difluoromethyl.
  • the substituent represented by R 6 is preferably C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl and C 1 -C 6 alkoxycarbonyl. More preferred are methyl, acetyl, propionyl, trifluoroacetyl, methoxycarbonyl and ethoxycarbonyl.
  • the substituent represented by R 7 preferably includes a hydrogen atom and methyl.
  • the substituent represented by R 8 preferably includes C 1 -C 4 alkyl, and more preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i- Examples include butyl, t-butyl or phenyl, and very preferably methyl and ethyl.
  • examples of r representing the number of oxygen atoms on the sulfur atom include 0, 1, and 2.
  • the solvent that can be used in the reaction of the present invention is not particularly limited as long as it is inert to the reaction.
  • it may be substituted with a halogen atom such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, or mesitylene.
  • Aromatic hydrocarbons or fats that may be substituted with halogen atoms such as n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylcyclohexane, methylene chloride or 1,2-dichloroethane
  • Aromatic hydrocarbons diethyl ether, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, ethers such as dimethoxyethane, nitriles such as acetonitrile and propionitrile, esters such as ethyl acetate and butyl acetate, methanol, Ethanol etc.
  • Examples include alcohols, amines such as triethylamine, tributylamine, pyridine, nitromethane, nitroethane, N, N-dimethylformamide, dimethyl sulfoxide, water, supercritical fluid, etc., preferably toluene, chlorobenzene, n-hexane, n- Heptane, cyclohexane, methylene chloride, 1,2-dichloroethane, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, dimethoxyethane, acetonitrile, propionitrile, ethyl acetate, methanol, nitromethane, N, N-dimethylformamide or dimethyl Sulfoxide, particularly preferably toluene for the production of (2) from (1), toluene, methanol, N, N-dimethyl for the production of (1) from (3) In the case where (3) is
  • toluene In the case of producing (1), toluene, methanol, N, N-dimethylformamide or dimethyl sulfoxide. These may be used singly or as a mixture of two or more.
  • a mixed solvent of toluene and cyclopentyl methyl ether, t-butyl methyl ether, or dimethoxyethane is preferable from the viewpoint of avoiding a cryogenic reaction such as ⁇ 78 ° C.
  • the amount of such a solvent to be used is not particularly limited, but is usually 0.01 to 50% by weight with respect to the aromatic ketone compound, substituted silyl ether compound, 1- (substituted phenyl) -1-substituted alcohol compound or aromatic ester compound. Parts, preferably 0.05 to 25 parts by weight, particularly preferably 0.1 to 10 parts by weight.
  • Examples of the catalyst that can be used in the reaction of the present invention include sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, potassium carbonate, sodium carbonate, barium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, acetic acid.
  • the amount of such a catalyst used is not particularly limited.
  • the amount is usually 0.1 to 10 parts by weight.
  • 1 mol of the aromatic aldehyde compound is used.
  • it is usually 0.001 to 1 times mol, preferably 0.005 to 0.5 times mol, particularly preferably 0.005 to 0.1 times mol.
  • Examples of the oxidation catalyst that can be used in the reaction of the present invention include 2,2,6,6-tetramethylpiperidine-1-oxyl, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 2-azaadamantane-N-oxyl, 1 -Methyl-2-azaadamantane-N-oxyl, 1,3-dimethyl-2-azaadamantane-N-oxyl and the like, and preferably 2,2,6,6-tetramethylpiperidine-1-oxyl, for example 2-azaadamantane-N-oxyl.
  • the amount of the oxidation catalyst used is not particularly limited, but is usually 0 to 0.1 times mol, preferably 0.00005 to 1 mol per 1 mol or 1 part by weight of 1- (substituted phenyl) -1-substituted alcohol compound. It is 0.05 times mole.
  • Additives that can be used in the reaction of the present invention include tetra-n-butylammonium fluoride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, acetic acid tetra-n-butylammonium, hydrogen sulfate tetra-n- Butyl ammonium, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium bromide, potassium bromide, barium hydroxide, calcium hydroxide, barium carbonate, calcium carbonate, sodium acetate, Potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium methoxide, potassium tert-butoxide, hydrochloric acid, trimethylamine, triethylamine, tri-n-butylamine, cinchonidine, Examples include methylamine-N
  • tetra-n-butylammonium chloride tetra-n-butylammonium bromide
  • sulfuric acid Hydrogen tetra-n-butylammonium, potassium carbonate, sodium bicarbonate, sodium bromide, potassium bromide, sodium carbonate, sodium acetate, potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, hydrochloric acid, trimethylamine , Triethylamine, tri-n-butylamine, tetra-n-butylammonium fluoride, tetra-n-butylammonium acetate or cesium fluoride.
  • additive used for the production of (13) from (12) and (5) for example, tetra-n-butylammonium fluoride or cesium fluoride is particularly preferable among the above-mentioned additives.
  • additive used for the production of (2) from (13) for example, hydrochloric acid, trimethylamine, triethylamine or tri-n-butylamine is preferable.
  • the amount of such additives used is not particularly limited, but for additives other than potassium carbonate, sodium hydrogen carbonate, sodium bromide and potassium bromide, 1 mol or 1- (substituted phenyl) -1-substituted alcohol compound is used.
  • the amount is usually 0.00001 to 0.1 times mol, preferably 0.00005 to 0.05 times mol based on parts by weight or 1 mol of the aromatic ester compound.
  • Examples of the oxidizing agent that can be used in the reaction of the present invention include perchloric acid or its salt, chloric acid or its salt, chlorous acid or its salt, hypochlorous acid or its salt, bromic acid or its salt, bromine
  • Examples include acids or salts thereof, hypobromite or salts thereof, periodic acid or salts thereof
  • examples of the salts include alkali metals (lithium, sodium and potassium) or alkaline earth metals (calcium and magnesium).
  • sodium perchlorate, sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, sodium bromate, sodium bromite, sodium hypobromite or potassium hypobromite Particularly preferred are sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite.
  • sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite are particularly preferred.
  • the amount of such an oxidizing agent to be used is not particularly limited, but is usually 1 to 2 times mol, preferably 1 to 1.5 times mol, per mol of 1- (substituted phenyl) -1-substituted alcohol compound.
  • Such an oxidizing agent is preferably used in the form of an aqueous solution containing a predetermined amount.
  • water-soluble organic solvents examples include dimethyl sulfoxide, sulfolane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, and N, N ′.
  • -Dimethylethyleneurea, hexamethylphosphoric triamide, acetonitrile, propionitrile, methanol, ethanol or the like can be mentioned, and dimethyl sulfoxide, N, N-dimethylformamide or methanol is preferable. These may be used singly or in combination of two or more.
  • the amount of such an organic solvent soluble in water is usually 0.01 to 10 parts by weight, preferably 0.01 to 5 parts by weight, particularly preferably 0. 0 parts by weight based on 1 part by weight of the aromatic aldehyde compound. 1 to 4 parts by weight.
  • water-insoluble organic solvents examples include aromatic hydrocarbons that may be substituted with a halogen atom such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, or mesitylene, or n.
  • Aliphatic hydrocarbons which may be substituted with halogen atoms such as -pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylcyclohexane, methylene chloride or 1,2-dichloroethane, Preferred is toluene, chlorobenzene, n-hexane, n-heptane, cyclohexane, methylene chloride or 1,2-dichloroethane. These may be used singly or in combination of two or more.
  • Examples of the acid that can be used in the reaction of the present invention include hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydroiodic acid, and inorganic acids such as nitric acid, sulfuric acid, phosphoric acid, chloric acid, and perchloric acid.
  • sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid
  • organic acids such as formic acid and acetic acid.
  • Examples of the fluorine source that can be used in the reaction of the present invention include tetrabutylammonium fluoride.
  • the aromatic aldehyde compound represented by the formula (4) which is a starting material for carrying out the present invention, is commercially available or can be produced by a known method.
  • the substituted silicon compound represented by the formula (5) which is a starting material for carrying out the present invention, is commercially available or can be produced by a known method.
  • the oxidant is added, and is usually ⁇ 20 to 120 ° C., preferably ⁇ 10 to 60 ° C., particularly preferably ⁇ 5 to 10 ° C., usually 1 minute to 24 hours, preferably about 10 minutes to 10 hours with stirring. What is necessary is just to make it react.
  • a substituted silyl ether compound represented by the formula (3) toluene, N, N-dimethylformamide, dimethyl sulfoxide, a solvent typified by methanol, an acid typified by hydrochloric acid and / or a fluorine source
  • the reaction is usually carried out at 0 to 120 ° C., preferably 10 to 80 ° C., usually 10 minutes to 96 hours, preferably 30 minutes to 72 hours. .
  • the reaction is allowed to proceed for 96 hours, preferably 15 minutes to 72 hours, and an additive typified by hydrochloric acid is added to the resulting reaction solution with or without the addition of a solvent typified by methanol.
  • the reaction may be carried out at ⁇ 120 ° C., preferably 10 ⁇ 80 ° C., usually for 10 minutes to 96 hours, preferably for 30 minutes to 72 hours.
  • an acid typified by hydrochloric acid and / or a fluorine source is added, and with stirring, usually 0 to 120 ° C., preferably 10 to 8
  • the reaction is usually performed at 10 ° C. for about 10 minutes to 96 hours, preferably about 30 minutes to 72 hours, and the reaction solution is subjected to extraction operation to obtain a solution containing the compound represented by formula (1).
  • Oxidation catalysts such as 2,6,6-tetramethylpiperidine-1-oxyl and 2-azaadamantane-N-oxyl, additives such as sodium bicarbonate or its aqueous solution and potassium bromide, hypochlorous acid
  • An oxidizing agent typified by sodium is charged, and under stirring, usually at ⁇ 20 to 120 ° C., preferably ⁇ 10 to 60 ° C., particularly preferably ⁇ 5 to 10 ° C., usually 1 minute to 24 hours, preferably 10 minutes to What is necessary is just to make it react for about 10 hours.
  • a benzoic acid ester compound represented by the formula (12) and a solvent typified by toluene and a substituted silicon compound represented by the formula (5) are charged in a reactor, and usually ⁇ 50 to 120 ° C. with stirring.
  • the catalyst may be added in the form of a solution or a solid, preferably at ⁇ 30 to 60 ° C., particularly preferably at ⁇ 20 to 10 ° C., and reacted.
  • a substituted silyl ether compound represented by the formula (3) toluene, N, N-dimethylformamide, dimethyl sulfoxide, a solvent typified by methanol, hydrochloric acid, triethylamine, tri-n-butylamine Additives to be added and reacted under stirring at a temperature of usually 0 to 120 ° C., preferably 10 to 80 ° C.
  • a benzoic acid ester compound represented by the formula (12) and a solvent typified by toluene and a substituted silicon compound represented by the formula (5) are charged in a reactor, and usually ⁇ 50 to 120 ° C. with stirring.
  • the catalyst is added in a solution or solid state at ⁇ 30 to 60 ° C., particularly preferably at ⁇ 20 to 10 ° C., and after the reaction, water is added, and a polar solvent typified by acetonitrile is added. What is necessary is just to cut
  • Example 1 Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone [Example 1-1] 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol 0.49 g (2.0 mmol), toluene 2.45 g, 2,2,6,6-tetramethylpiperidine-1-oxyl 5 mg (0.022 mmol), potassium bromide 26 mg (0.22 mmol), and distilled water 0.25 g were charged and cooled to 0 ° C.
  • Example 1-2 0.25 g (1.0 mmol) of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol, 0.74 g of toluene, 10 ⁇ l of 2-azaadamantane-N-oxyl (0.01 mmol / ml of toluene) Solution, 0.0001 mmol), 0.74 g of 5% aqueous sodium hydrogen carbonate solution was charged, and cooled to 0 ° C. Further, 0.8 ml (about 1.1 mmol) of an aqueous sodium hypochlorite solution was added and stirred at 0 ° C. for 3 hours.
  • Example 1-3 3- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol 0.98 g (4.0 mmol), toluene 2.94 g, 2,2,6,6-tetramethylpiperidine-1-oxyl 9 mg (0.038 mmol) and 1.47 g of 5% aqueous sodium hydrogen carbonate solution were charged and cooled to 0 ° C. Furthermore, 3.6 ml (about 4.4 mmol) of an aqueous sodium hypochlorite solution was added, and the mixture was stirred at 0 ° C. for 2 hours. To the reaction solution was added 0.10 g (0.8 mmol) of sodium sulfite, and the mixture was stirred at room temperature for 1 hour.
  • reaction solution was separated and extracted from the aqueous layer using 5.9 g of toluene.
  • the organic layers were combined to obtain 8.1 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone.
  • this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 0.95 g (yield 98%). ).
  • Example 1-4 A toluene solution containing 5.17 g of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone obtained by carrying out the same operation as in Example 1-3 was concentrated under reduced pressure, Purified by distillation. As a fraction at 84 to 89 ° C. (14 mmHg), 4.68 g of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was obtained.
  • Example 2 Synthesis of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane 1.67 g, toluene 3 .81 g, 1.90 g of methanol, 0.76 g of distilled water, and 0.76 g of concentrated hydrochloric acid were added and stirred at 30 ° C. for 4 hours. Distilled water (3.8 g) and toluene (3.8 g) were added to the reaction solution to separate the layers. Further, the aqueous layer was extracted with 7.6 g of toluene.
  • Example 3 Synthesis of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane 3.5 g (20 mmol) of 3,5-dichlorobenzaldehyde, 10.5 g of toluene, 1.75 g of dimethyl sulfoxide, tri 3.41 g (24 mmol) of fluoromethyltrimethylsilane and 55 mg (0.4 mmol) of potassium carbonate were charged and stirred at room temperature for 7 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography.
  • the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 3% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks for toluene and dimethyl sulfoxide).
  • 3.5 ml of cold distilled water was added and stirred at room temperature for 10 minutes. The reaction mixture was separated, and the organic layer was washed with saturated brine and concentrated under reduced pressure. 7.6 g of crude (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was obtained as a slightly yellow liquid.
  • Example 4 Synthesis of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol in one step [Example 4-1] 3.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 7.0 g of toluene, 1.75 g of N, N-dimethylformamide, 1.71 g (12 mmol) of trifluoromethyltrimethylsilane, and 42 mg (0.30 mmol) of potassium carbonate are charged. And stirred at room temperature for 20 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography.
  • the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks of toluene and N, N-dimethylformamide). Distilled water (1 ml) and concentrated hydrochloric acid (1 ml) were added to the reaction solution, followed by stirring at 60 ° C. for 2 hours and then at room temperature overnight. The reaction solution was separated and extracted from the aqueous layer using 7 g of toluene. The organic layers were combined and concentrated under reduced pressure.
  • Example 4-2 Charged 0.70 g (4.0 mmol) of 3,5-dichlorobenzaldehyde, 1.4 g of dimethyl sulfoxide, and 11 mg (0.08 mmol) of potassium carbonate, and heated to 30 ° C. 0.68 g (4.8 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 2 hours. Distilled water (0.4 ml) and concentrated hydrochloric acid (0.2 ml) were added to the reaction solution, and the mixture was stirred at 30 ° C. for 1 hour.
  • the reaction solution was diluted with 4 ml of distilled water, and 10 ml of toluene was added for liquid separation. Further, the aqueous layer was extracted with 5 ml of toluene. The organic layers were combined to obtain 14.2 g of a solution containing 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol.
  • this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol was 0.91 g (yield) 93%).
  • Example 5 Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone in one step
  • Example 5-1 3.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 5.3 g of toluene, 1.71 g (12 mmol) of trifluoromethyltrimethylsilane, 0.16 g (0.5 mmol) of tetra-n-butylammonium bromide, 41 mg of sodium acetate ( 0.5 mmol), and stirred at 30 ° C. for 2 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography.
  • the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak).
  • Distilled water 0.88 g, concentrated hydrochloric acid 0.87 g, and methanol 2.6 g were added to the reaction solution, and the mixture was stirred at 30 ° C. for 3 hours.
  • 5.3 g of distilled water and 5.3 g of toluene were added for liquid separation, and the aqueous layer was extracted with 10.5 g of toluene.
  • Example 5-2 1.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 5.3 g of toluene, 1.1 g of dimethyl sulfoxide, and 28 mg (0.2 mmol) of potassium carbonate were charged and heated to 30 ° C. 1.71 g (12 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 3 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography.
  • the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 5% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks for toluene and dimethyl sulfoxide). Distilled water (0.88 g), concentrated hydrochloric acid (0.88 g), and methanol (2.1 g) were added to the reaction solution, and the mixture was stirred at 30 ° C. for 3 hours and then at room temperature overnight. The reaction solution was separated by adding 5.3 g of distilled water, and extracted from the aqueous layer with 10.5 g of toluene.
  • Example 5-3 2.1 g (12 mmol) of 3,5-dichlorobenzaldehyde, 6.7 g of toluene, and 90 mg (0.3 mmol) of tetra-n-butylammonium acetate were charged and heated to 30 ° C. 1.90 g (13.4 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 1.5 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography.
  • the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 97. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak).
  • Distilled water (0.88 g), concentrated hydrochloric acid (0.88 g) and methanol (5.3 g) were added to the reaction mixture, and the mixture was stirred at 30 ° C. for 1 hour and then at room temperature overnight.
  • Distilled water (10.5 g) and toluene (10.5 g) were added to the reaction solution, and the mixture was separated. The aqueous layer was extracted with 10.5 g of toluene.
  • Example 6 Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone from 3,5-dichlorobenzoic acid methyl ester
  • Example 6-1 3.075 g (15 mmol) of 3,5-dichlorobenzoic acid methyl ester, 30 mL of toluene and 2.67 g (18.75 mmol) of trifluoromethyltrimethylsilane were charged and cooled to ⁇ 20 ° C. 90 ⁇ L (0.6 mol%) of a tetrahydrofuran solution of tetra-n-butylammonium fluoride having a concentration of 1M was dropped, and the mixture was stirred for 30 minutes while maintaining the temperature at ⁇ 20 ° C.
  • reaction solution was separated and extracted from the aqueous layer with 10 mL of toluene. The organic layers were combined and the solvent was distilled off. Hexane 50mL was added, methanol was azeotropically distilled off using Dean Stark, and distilled under reduced pressure to obtain 3.15 g (78-82 ° C./20 mmHg) fraction. A small amount of this was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. The area percentage of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 99.9% (UV It was detected at a wavelength of 220 nm with a detector.) (Yield 86.5%).
  • Example 6-2 A mixture of 41.01 g (200 mmol) of 3,5-dichlorobenzoic acid methyl ester, 266 mL of toluene, 114 mL of dimethoxyethane, and 0.61 g (4 mmol) of cesium fluoride was cooled to ⁇ 20 ° C. 34.13 g (240 mmol) of trifluoromethyltrimethylsilane was added dropwise, and the mixture was stirred for 30 minutes while maintaining the temperature at ⁇ 20 ° C. A small amount of the reaction solution was taken, diluted with water and acetonitrile, and analyzed by high performance liquid chromatography.
  • Example 7 Synthesis of (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane 3,5-dichlorobenzoic acid methyl ester 0.4101 g (2 mmol), heptane 4.8 mL, Trifluoromethyltrimethylsilane 0.3697 g (2.6 mmol) was charged and cooled to 0 ° C. A tetrahydrofuran solution of tetra-n-butylammonium fluoride having a concentration of 1 M in 40 ⁇ L was dissolved in 0.2 mL of toluene, which was added dropwise, and stirred for 30 minutes while maintaining the temperature at 0 ° C.
  • reaction solution A small amount was taken, diluted with water and acetonitrile, and analyzed by high performance liquid chromatography. As a result, (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane was obtained. The area percentage was 86.3% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak).
  • Example 8 Synthesis of 2,2,2-trifluoro-1- (3- (trifluoromethyl) phenyl) ethanone 3- (trifluoromethyl) benzoic acid methyl ester 25.0 g (122.4 mmol), toluene 140 g, dimethoxyethane 60 g Then, 0.93 g (6.12 mmol) of cesium fluoride was charged and cooled to ⁇ 20 ° C. 20.9 g (147.0 mmol) of trifluoromethyltrimethylsilane was added dropwise, and the mixture was stirred for 2 hours while maintaining the temperature at ⁇ 20 ° C. Distilled water (20 mL) was added to the reaction solution to room temperature, followed by liquid separation.
  • the production method of the present invention is useful as a production method of aromatic ketone compounds, substituted silyl ether compounds and 1- (substituted phenyl) -1-substituted alcohol compounds, which are compounds useful as intermediates for agricultural chemicals, pharmaceuticals and various chemicals. It is.

Abstract

Provided are processes for production of intermediates for the production of pest control agents and novel intermediates for the production thereof. A process for the production of substituted silyl ethers represented by general formula (3) which comprises using an aromatic aldehyde represented by general formula (4) and a substituted silicon compound represented by general formula (5) as the starting materials and reacting both with each other in an organic solvent in the presence or absence of an additive and in the presence of a catalyst; a process for producing 1-(substituted phenyl)-1-substituted alcohols represented by general formula (1) from (4) and (5) through (3) in one step; a process for producing aromatic ketones represented by general formula (2) by oxidation of (1); a process for producing (2) from (4) and (5) through (3) and (1) in one step; a process for the production of substituted silyl ethers represented by general formula (13) which comprises using an aromatic ester represented by general formula (12) and (5) as the starting materials and reacting both with each other; a process for producing (2) from (12) and (5) through (13) in one step; and 1-(substituted phenyl)-2,2,2-trifluoroethanols and substituted trimethyl- silyl ethers, which serve as novel intermediates for the processes.

Description

１－（置換フェニル）－１－置換シリルエーテル、アルコールまたはケトンの製造方法および中間体Process for producing 1- (substituted phenyl) -1-substituted silyl ethers, alcohols or ketones and intermediates
　本発明は、医農薬あるいは電子材料等の機能性材料の製造中間体として有用な芳香族ケトン化合物、置換シリルエーテル化合物および１－（置換フェニル）－１－置換アルコール化合物の製造方法、ならびに、１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物および置換トリメチルシリルエーテル化合物に関するものである。 The present invention relates to a process for producing aromatic ketone compounds, substituted silyl ether compounds and 1- (substituted phenyl) -1-substituted alcohol compounds useful as intermediates for the production of functional materials such as medical and agricultural chemicals or electronic materials, and 1 The present invention relates to a-(substituted phenyl) -2,2,2-trifluoroethanol compound and a substituted trimethylsilyl ether compound.
　芳香族アルデヒド化合物を出発原料として置換シリルエーテル化合物又は１－（置換フェニル）－１－置換アルコール化合物を製造する方法は、幾つか知られている（例えば、特許文献１および２、非特許文献１～１２）。
　また、１－（置換フェニル）－１－置換アルコール化合物を原料として芳香族ケトン化合物を製造する方法も知られている（例えば、特許文献３および４、非特許文献１３～１７）。 Several methods for producing a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound using an aromatic aldehyde compound as a starting material are known (for example, Patent Documents 1 and 2, Non-Patent Document 1). ~ 12).
Also known are methods for producing aromatic ketone compounds using 1- (substituted phenyl) -1-substituted alcohol compounds as raw materials (for example, Patent Documents 3 and 4, Non-Patent Documents 13 to 17).
先行技術文献Prior art documents
特開平７－１１８１８８号明細書Japanese Patent Application Laid-Open No. 7-118188 独国特許出願公開第３８０５５３４号明細書German Patent Application Publication No. 3805534 米国特許出願第２００５１３１２１６号明細書US Patent Application No. 20051121616 独国特許出願公開第４２０１４３５号明細書German Patent Application Publication No. 4141435 米国特許出願第２００４２０４３８６号明細書US Patent Application No. 2004024386 国際公開第２００７／０７４７８９号パンフレットInternational Publication No. 2007/074789 Pamphlet 国際公開第２００９／００１９４２号パンフレットInternational Publication No. 2009/001942 Pamphlet
　特許文献２、非特許文献９～１２に記載の、フッ素化合物を触媒とする方法は従来から知られているが、必ずしも工業化に適した方法とは言えない。特許文献１ではトリエチルアミン等の有機塩基を用いているが、使用量が触媒量では収率が低く、工業的製法としては満足いくものではない。非特許文献１～７では何れも大量入手の困難な資材や重金属を用いており、製造コストや廃棄物の増大に繋がり、工業的製法としては満足いくものではない。非特許文献８には比較的安価な触媒を用いた方法も記載してあるが、回収の困難な溶媒を必要としているため、工業的製造法として満足いくものではない。 Although the methods described in Patent Document 2 and Non-Patent Documents 9 to 12 using a fluorine compound as a catalyst have been conventionally known, they are not necessarily suitable for industrialization. In Patent Document 1, an organic base such as triethylamine is used, but if the amount used is a catalyst amount, the yield is low, which is not satisfactory as an industrial production method. Non-patent documents 1 to 7 all use materials and heavy metals that are difficult to obtain in large quantities, leading to an increase in manufacturing costs and waste, which is not satisfactory as an industrial production method. Non-Patent Document 8 also describes a method using a relatively inexpensive catalyst, but it is not satisfactory as an industrial production method because it requires a solvent that is difficult to recover.
　特許文献３に記載の方法は、反応後、強い悪臭を有する化合物が副生するため、工業的製造には不向きである。特許文献４に記載の方法は生成物の収率が高くはなく、工業的製造法として満足いくものではない。特許文献１３～１７に記載の方法では、大量入手の困難な資材や重金属を用いており、製造コストや廃棄物の増大に繋がり、工業的製法としては満足いくものではない。 The method described in Patent Document 3 is not suitable for industrial production because a compound having a strong odor is by-produced after the reaction. The method described in Patent Document 4 is not satisfactory as an industrial production method because the yield of the product is not high. The methods described in Patent Documents 13 to 17 use materials and heavy metals that are difficult to obtain in large quantities, leading to an increase in manufacturing costs and waste, and are not satisfactory as an industrial production method.
　このように、既存の方法には、芳香族アルデヒド化合物を出発原料として置換シリルエーテル化合物又は１－（置換フェニル）－１－置換アルコール化合物を、高価な試剤や重金属等を使用せずに製造する方法が知られておらず、改善の余地を残している。 Thus, in the existing method, a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound is produced using an aromatic aldehyde compound as a starting material without using expensive reagents or heavy metals. The method is unknown and leaves room for improvement.
　また、１－（置換フェニル）－１－置換アルコール化合物を原料として芳香族ケトン化合物を、回収容易な低極性溶媒中で、大量入手の困難な試剤や重金属等を使用せずに製造する方法が知られておらず、改善の余地を残している。 Also, there is a method for producing an aromatic ketone compound from a 1- (substituted phenyl) -1-substituted alcohol compound as a raw material in a low-polarity solvent that can be easily recovered without using reagents or heavy metals that are difficult to obtain in large quantities. It is not known and leaves room for improvement.
　特許文献５では４－ニトロ安息香酸メチルから２，２，２－トリフルオロ－１－（４－ニトロフェニル）エタノンを合成した例のみが示されており、また収率は４７％と中程度であり、工業的製法として一般化することは難しかった。特許文献６や７に記載のようにジメトキシエタン溶媒中で比較的高温で反応を行った場合、目的物のトリフルオロアセトフェノンにさらにトリフルオロメチルトリメチルシランが反応して生じたと思われる、トリフルオロメチル基が２つ入った副生成物が比較的多く生成するために、目的物の収率が低下するという問題があった。非特許文献１８、２０に記載の方法では－７８℃の極低温で反応を行わなければならず、工業的製法としては満足いくものではなかった。非特許文献１９に記載の方法は基質によっては目的物のカルボニル化合物がさらに反応した副生物が生成するため、高選択的、高収率で目的物のカルボニル化合物を得ることは困難な場合があった。非特許文献９に記載の方法はフッ化セシウムを触媒として用いているが、トルエンに代表される工業的によく使用される低極性溶媒では反応が進行しないこと、さらに、反応基質を無溶媒で混合したところに触媒のフッ化セシウムを固体で加えるという反応暴走の危険性が非常に高い方法であることから、工業的製法としては満足のいくものではなかった。 Patent Document 5 shows only an example in which 2,2,2-trifluoro-1- (4-nitrophenyl) ethanone was synthesized from methyl 4-nitrobenzoate, and the yield was about 47%. It was difficult to generalize as an industrial production method. When the reaction is carried out at a relatively high temperature in a dimethoxyethane solvent as described in Patent Documents 6 and 7, trifluoromethyltrimethylsilane is considered to be produced by further reaction of the target trifluoroacetophenone with trifluoromethyltrimethylsilane. There was a problem that the yield of the target product was lowered because a relatively large amount of by-product containing two groups was produced. In the methods described in Non-Patent Documents 18 and 20, the reaction must be performed at an extremely low temperature of −78 ° C., which is not satisfactory as an industrial production method. In the method described in Non-Patent Document 19, a by-product is produced by further reacting the target carbonyl compound depending on the substrate, so it may be difficult to obtain the target carbonyl compound with high selectivity and high yield. It was. The method described in Non-Patent Document 9 uses cesium fluoride as a catalyst. However, the reaction does not proceed in a low-polar solvent commonly used in industry such as toluene, and the reaction substrate is used without a solvent. Since the risk of runaway reaction of adding cesium fluoride as a catalyst to the mixture as a solid is extremely high, it was not satisfactory as an industrial production method.
　このように、既存の方法には、安息香酸エステル化合物を出発原料として置換シリルエーテル化合物又は１－（置換フェニル）－１－置換カルボニル化合物を、トルエンに代表される工業的によく使用される低極性溶媒中で高収率、高選択的に製造する方法が－７８℃という極低温で反応を行う以外には知られておらず、改善の余地を残していた。 As described above, in the existing method, a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted carbonyl compound using a benzoate ester compound as a starting material is used in a low-cost industrially typical process represented by toluene. A method for producing a high yield and high selectivity in a polar solvent is not known except that the reaction is carried out at an extremely low temperature of −78 ° C., leaving room for improvement.
　本発明者らは、このような状況に鑑み、鋭意検討した結果、芳香族アルデヒド化合物を出発原料として置換シリルエーテル化合物又は１－（置換フェニル）－１－置換アルコール化合物を、トルエンに代表される低極性溶媒中で、水に可溶な溶媒の存在下又は非存在下、炭酸カリウム等の入手容易な資材を触媒として用いて反応を行い、高い収率で製造する方法を見出し、発明に至った。
　また、１－（置換フェニル）－１－置換アルコール化合物を原料として芳香族ケトン化合物を、トルエンに代表される低極性溶媒中で、酸化触媒および添加物の存在下、次亜塩素酸塩等の酸化剤を用いて反応を行い、高い収率で製造する方法を見出し、発明に至った。
　また、安息香酸エステル化合物を出発原料として置換シリルエーテル化合物又は１－（置換フェニル）－１－置換カルボニル化合物を、トルエンに代表される低極性溶媒中で、－50℃より高い温度で、触媒を用いて反応を行い、高選択的、高収率に製造する方法を見出し、発明に至った。 As a result of diligent studies in view of such circumstances, the present inventors have represented a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound as a starting material by using an aromatic aldehyde compound as a starting material. In a low-polarity solvent, in the presence or absence of a water-soluble solvent, the reaction was carried out using an easily available material such as potassium carbonate as a catalyst, and a method for producing in high yield was found, leading to the invention. It was.
In addition, aromatic ketone compounds using 1- (substituted phenyl) -1-substituted alcohol compounds as raw materials in hypopolar solvents typified by toluene, such as hypochlorite in the presence of an oxidation catalyst and additives. A reaction was carried out using an oxidant to find a method for producing in a high yield, leading to the invention.
Further, a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted carbonyl compound using a benzoic acid ester compound as a starting material is subjected to a catalyst at a temperature higher than −50 ° C. in a low polarity solvent typified by toluene. The present invention has been carried out to find a method of producing a product with high selectivity and high yield, leading to the invention.
　すなわち、本発明は、
〔１〕　式（１）：
Figure JPOXMLDOC01-appb-C000025
 　［式中、Ｒ1は、Ｃ1～Ｃ6ハロアルキル又はＣ3～Ｃ8ハロシクロアルキルを表し、
　Ｘは、ハロゲン原子、シアノ、ニトロ、－ＳＦ5、Ｃ1～Ｃ6アルキル、Ｃ3～Ｃ8シクロアルキル、Ｃ1～Ｃ6アルケニル、Ｃ1～Ｃ6アルキニル、シアノ（Ｃ1～Ｃ6）アルキル、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルケニル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル、－ＯＨ、－ＯＲ5、ベンジルオキシ、－ＮＨ2、－Ｎ（Ｒ7）Ｒ6、－Ｓ（Ｏ）rＲ5又はフェニルスルホニルオキシを表し、ｍが２以上を表すとき、各々のＸは互いに同一であっても又は互いに相異なっていてもよく、
　Ｒ5は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ4アルコキシ（Ｃ1～Ｃ4）アルキル、Ｃ1～Ｃ6ハロアルキル又はＣ1～Ｃ3ハロアルコキシ（Ｃ1～Ｃ3）ハロアルキルを表し、
　Ｒ6は、Ｃ1～Ｃ6アルキル、－ＣＨＯ、Ｃ1～Ｃ6アルキルカルボニル、Ｃ1～Ｃ6ハロアルキルカルボニル、Ｃ1～Ｃ6アルコキシカルボニル、Ｃ1～Ｃ6アルキルチオカルボニル、Ｃ1～Ｃ6アルコキシチオカルボニル、Ｃ1～Ｃ6アルキルジチオカルボニル、Ｃ1～Ｃ6アルキルスルホニル又はＣ1～Ｃ6ハロアルキルスルホニルを表し、
　Ｒ7は、水素原子又はＣ1～Ｃ6アルキルを表し、
　ｍは、０～５の整数を表し、
　ｒは、０～２の整数を表す。］　で表される１－（置換フェニル）－１－置換アルコール化合物を酸化触媒および添加物の存在下、酸化剤と反応させることによる式（２）：
Figure JPOXMLDOC01-appb-C000026
 　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］で表される芳香族ケトン化合物の製造方法。 That is, the present invention
[1] Formula (1):
Figure JPOXMLDOC01-appb-C000025
 [Wherein R 1 represents C 1 -C 6 haloalkyl or C 3 -C 8 halocycloalkyl,
X is a halogen atom, cyano, nitro, —SF 5 , C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, cyano (C 1 -C 6 ) Alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkenyl, hydroxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 , benzyloxy, —NH 2 , —N (R 7 ) R 6 , —S (O) r R 5 or Represents phenylsulfonyloxy, and when m represents 2 or more, each X may be the same as or different from each other;
R 5 represents C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 6 haloalkyl or C 1 -C 3 haloalkoxy (C 1 -C 3 ) haloalkyl. ,
R 6 is C 1 -C 6 alkyl, —CHO, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C Represents 6 alkoxythiocarbonyl, C 1 -C 6 alkyldithiocarbonyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl,
R 7 represents a hydrogen atom or C 1 -C 6 alkyl,
m represents an integer of 0 to 5,
r represents an integer of 0-2. A compound represented by formula (2) by reacting a 1- (substituted phenyl) -1-substituted alcohol compound represented by the following formula with an oxidizing agent in the presence of an oxidation catalyst and an additive:
Figure JPOXMLDOC01-appb-C000026
 [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of the aromatic ketone compound represented by this.
〔２〕　式（３）：
Figure JPOXMLDOC01-appb-C000027
 　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表し、Ｒ2、Ｒ3およびＲ4は、Ｃ1～Ｃ6アルキル又は芳香族基を表す。］　で表される置換シリルエーテル化合物を水を添加してまたは添加しないで、他の有機溶媒を添加してまたは添加しないで、酸および／またはフッ素源と反応させることによる前記式（１）：
Figure JPOXMLDOC01-appb-C000028
 　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］で表される１－（置換フェニル）－１－置換アルコール化合物の製造方法。 [2] Formula (3):
Figure JPOXMLDOC01-appb-C000027
 [Wherein R 1 , X, and m represent the same meaning as described above, and R 2 , R 3, and R 4 represent C 1 -C 6 alkyl or an aromatic group. The above-described formula (1) is obtained by reacting the substituted silyl ether compound represented by the formula (1) with or without addition of water and with or without the addition of another organic solvent:
Figure JPOXMLDOC01-appb-C000028
 [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of 1- (substituted phenyl) -1-substituted alcohol compound represented by this.
〔３〕　式（４）：
Figure JPOXMLDOC01-appb-C000029
 　［式中、Ｘ、ｍは前記と同様の意味を表す。］　で表される芳香族アルデヒド化合物と
式（５）：
Figure JPOXMLDOC01-appb-C000030
 　［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを溶媒中反応させることによる前記式（３）：
Figure JPOXMLDOC01-appb-C000031
 ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｘ、ｍは前記と同様の意味を表す。］で表される置換シリルエーテル化合物の製造方法。
〔４〕　溶媒が水に不溶な有機溶媒であることを特徴とする〔３〕記載の製造方法。
〔５〕　溶媒が水に可溶な有機溶媒であることを特徴とする〔３〕記載の製造方法。
〔６〕　溶媒が水に不溶な有機溶媒であり、水に可溶な有機溶媒を混合することを特徴とする〔３〕記載の製造方法。 [3] Formula (4):
Figure JPOXMLDOC01-appb-C000029
 [Wherein, X and m represent the same meaning as described above. ] An aromatic aldehyde compound represented by the formula (5):
Figure JPOXMLDOC01-appb-C000030
 [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. The above formula (3) by reacting with a substituted silicon compound represented by the following formula:
Figure JPOXMLDOC01-appb-C000031
 [Wherein, R 1 , R 2 , R 3 , R 4 , X, m represent the same meaning as described above. ] The manufacturing method of the substituted silyl ether compound represented by this.
[4] The production method according to [3], wherein the solvent is an organic solvent insoluble in water.
[5] The method according to [3], wherein the solvent is an organic solvent soluble in water.
[6] The production method according to [3], wherein the solvent is an organic solvent insoluble in water and an organic solvent soluble in water is mixed.
〔７〕　前記式（４）：
Figure JPOXMLDOC01-appb-C000032
 ［式中、Ｘ、ｍは前記と同様の意味を表す。］　で表される芳香族アルデヒド化合物と前記式（５）：
Figure JPOXMLDOC01-appb-C000033
 ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを溶媒中反応させ、次いで、水を添加してまたは添加しないで、他の有機溶媒を添加してまたは添加しないで、酸および／またはフッ素源と反応させることにより前記式（１）：
Figure JPOXMLDOC01-appb-C000034
 ［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換アルコール化合物を１工程で製造する方法。 [7] Formula (4):
Figure JPOXMLDOC01-appb-C000032
 [Wherein, X and m represent the same meaning as described above. ] An aromatic aldehyde compound represented by the formula (5):
Figure JPOXMLDOC01-appb-C000033
 [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. And then reacting with the acid and / or fluorine source with or without the addition of water and with or without the addition of other organic solvents. According to the formula (1):
Figure JPOXMLDOC01-appb-C000034
 [Wherein R 1 , X and m represent the same meaning as described above. A method for producing a 1- (substituted phenyl) -1-substituted alcohol compound represented by the following formula:
〔８〕　前記式（４）で表される化合物と前記式（５）で表される化合物を反応させて得られる前記式（１）で表される化合物を含有する溶液を原料として用いる〔１〕記載の芳香族ケトン化合物の製造方法。 [8] A solution containing the compound represented by the formula (1) obtained by reacting the compound represented by the formula (4) and the compound represented by the formula (5) is used as a raw material [1. ] The manufacturing method of the aromatic ketone compound of description.
〔９〕　Ｘは、ハロゲン原子、シアノ、ニトロ、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6ハロアルキル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、シアノ（Ｃ1～Ｃ6）アルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル、－ＯＨ、－ＯＲ5、－ＮＨ2又は－Ｎ（Ｒ7）Ｒ6を表し、ｍが２以上を表すとき、各々のＸは互いに同一であっても又は互いに相異なっていてもよく、
　Ｒ6は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6アルキルカルボニル、Ｃ1～Ｃ6ハロアルキルカルボニル又はＣ1～Ｃ6アルコキシカルボニルを表す〔１〕～〔８〕のいずれかに記載の製造方法。 [9] X is a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1- C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 , —NH 2 or —N (R 7 ) R 6 and when m represents 2 or more, each X may be the same as or different from each other,
The production according to any one of [1] to [8], wherein R 6 represents C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, or C 1 -C 6 alkoxycarbonyl. Method.
〔１０〕　式（６）：
Figure JPOXMLDOC01-appb-C000035
 ［式中、Ｙは、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、
　Ｚは、塩素原子、臭素原子、よう素原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。 [10] Formula (6):
Figure JPOXMLDOC01-appb-C000035
 [Wherein Y represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio;
Z represents a chlorine atom, bromine atom, iodine atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
〔１１〕　式（７）：
Figure JPOXMLDOC01-appb-C000036
 　［式中、Ｚは前記と同様の意味を表し、
　Ｗは、臭素原子、よう素原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。 [11] Formula (7):
Figure JPOXMLDOC01-appb-C000036
 [Wherein Z represents the same meaning as described above,
W represents a bromine atom, an iodine atom, a C 1 -C 6 haloalkyl, a C 1 -C 6 haloalkoxy or a C 1 -C 6 haloalkylthio. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
〔１２〕　式（８）：
Figure JPOXMLDOC01-appb-C000037
 　［式中、Ｙ1は、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、Ｙ2は、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、Ｚは前記と同様の意味を表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。 [12] Formula (8):
Figure JPOXMLDOC01-appb-C000037
 [Wherein Y 1 represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio, Y 2 represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio is represented, and Z represents the same meaning as described above. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
〔１３〕　式（９）：
Figure JPOXMLDOC01-appb-C000038
 ［式中、Ｙ、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。 [13] Formula (9):
Figure JPOXMLDOC01-appb-C000038
 [Wherein Y and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
〔１４〕　式（１０）：
Figure JPOXMLDOC01-appb-C000039
 ［式中、Ｗ、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。 [14] Formula (10):
Figure JPOXMLDOC01-appb-C000039
 [Wherein W and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
〔１５〕　式（１１）：
Figure JPOXMLDOC01-appb-C000040
 ［式中、Ｙ1、Ｙ2、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。 [15] Formula (11):
Figure JPOXMLDOC01-appb-C000040
 [Wherein Y 1 , Y 2 and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
〔１６〕　式（１２）：
Figure JPOXMLDOC01-appb-C000041
 　［式中、Ｒ8は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6アルケニル、Ｃ1～Ｃ6アルキニル、Ｃ3～Ｃ8シクロアルキル、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルケニル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル又は芳香族基を表し、Ｘ、ｍは前記と同様の意味を表す。］　で表される安息香酸エステル化合物を式（５）：
Figure JPOXMLDOC01-appb-C000042
 ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物と反応させることによる式（１３）：
Figure JPOXMLDOC01-appb-C000043
 ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される置換シリルエーテル化合物の製造方法。 [16] Formula (12):
Figure JPOXMLDOC01-appb-C000041
 [Wherein R 8 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 halo. Alkenyl, hydroxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocyclo Represents an alkyl or aromatic group, and X and m represent the same meaning as described above. A benzoic acid ester compound represented by the formula (5):
Figure JPOXMLDOC01-appb-C000042
 [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. ] Formula (13) by making it react with the substituted silicon compound represented by these:
Figure JPOXMLDOC01-appb-C000043
 [Wherein, R 1 , R 2 , R 3 , R 4 , R 8 , X, m represent the same meaning as described above. ] The manufacturing method of the substituted silyl ether compound represented by these.
〔１７〕　式（１３）：
Figure JPOXMLDOC01-appb-C000044
 　［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される置換シリルエーテル化合物を反応させることによる式（２）：
Figure JPOXMLDOC01-appb-C000045
 　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換カルボニル化合物の製造方法。 [17] Formula (13):
Figure JPOXMLDOC01-appb-C000044
 [Wherein, R 1 , R 2 , R 3 , R 4 , R 8 , X, m represent the same meaning as described above. ] Formula (2) by making the substituted silyl ether compound represented by these react:
Figure JPOXMLDOC01-appb-C000045
 [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of 1- (substituted phenyl) -1-substituted carbonyl compound represented by these.
〔１８〕　式（１２）：
Figure JPOXMLDOC01-appb-C000046
 　［式中、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される安息香酸エステル化合物と式（５）：
Figure JPOXMLDOC01-appb-C000047
 ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを反応させることにより、式（２）：
Figure JPOXMLDOC01-appb-C000048
 ［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換カルボニル化合物を１工程で製造する製造方法。 [18] Formula (12):
Figure JPOXMLDOC01-appb-C000046
 [Wherein R 8 , X and m represent the same meaning as described above. And a benzoic acid ester compound represented by the formula (5):
Figure JPOXMLDOC01-appb-C000047
 [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. By reacting with a substituted silicon compound represented by the formula (2):
Figure JPOXMLDOC01-appb-C000048
 [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method which manufactures the 1- (substituted phenyl) -1-substituted carbonyl compound represented by these by 1 process.
〔１９〕　ハロゲンで置換されていてもよい脂肪族炭化水素、ハロゲンで置換されていてもよい芳香族炭化水素またはその少なくとも一方を含む混合溶媒を溶媒として用いる〔１６〕ないし〔１８〕のいずれかに記載の製造方法。
〔２０〕　－５０℃より高い温度で反応を行う〔１６〕ないし〔１９〕のいずれかに記載の製造方法。 [19] Any of [16] to [18], wherein an aliphatic hydrocarbon optionally substituted with halogen, an aromatic hydrocarbon optionally substituted with halogen, or a mixed solvent containing at least one of them is used as a solvent. The manufacturing method as described in.
[20] The production method according to any one of [16] to [19], wherein the reaction is performed at a temperature higher than −50 ° C.
　本発明の製造方法により、医農薬あるいは電子材料等の機能性材料の製造中間体の合成に有用な芳香族ケトン化合物、置換シリルエーテル化合物又は１－（置換フェニル）－１－置換アルコール化合物を、１－（置換フェニル）－１－置換アルコール化合物、芳香族アルデヒド化合物、置換ケイ素化合物又は置換シリルエーテル化合物、安息香酸エステル化合物を出発原料として、触媒等の試剤を適切に選択し、トルエンなどの工業的に使用しやすい溶媒中で、トリフルオロメチル基が２つ入った副生成物の生成を抑制しつつ、高収率、高選択的に製造することができ、それをもって工業的生産に有益な方法を提供できる。 By the production method of the present invention, an aromatic ketone compound, a substituted silyl ether compound or a 1- (substituted phenyl) -1-substituted alcohol compound useful for the synthesis of a production intermediate of a functional material such as a medical pesticide or an electronic material, Starting from 1- (substituted phenyl) -1-substituted alcohol compounds, aromatic aldehyde compounds, substituted silicon compounds or substituted silyl ether compounds, and benzoic acid ester compounds, reagents such as catalysts are appropriately selected, and industries such as toluene In a solvent that is easy to use, it can be produced with high yield and high selectivity while suppressing the formation of a by-product containing two trifluoromethyl groups, which is useful for industrial production. Can provide a method.
　本願記載の一般式（１）、（３）、（６）～（１１）又は（１３）で表される化合物には、１個以上の不斉炭素原子の存在に起因する光学活性体が存在するが、本願記載の化合物は全ての光学活性体又はラセミ体を包含する。 The compound represented by the general formula (1), (3), (6) to (11) or (13) described in the present application has an optically active substance resulting from the presence of one or more asymmetric carbon atoms. However, the compounds described herein include all optically active forms or racemates.
　本願記載の化合物のうちで、常法に従って酸付加塩にすることができるものは、例えば、フッ化水素酸、塩酸、臭化水素酸、よう化水素酸等のハロゲン化水素酸の塩、硝酸、硫酸、燐酸、塩素酸、過塩素酸等の無機酸の塩、メタンスルホン酸、エタンスルホン酸、トリフルオロメタンスルホン酸、ベンゼンスルホン酸、p-トルエンスルホン酸等のスルホン酸の塩、ギ酸、酢酸、プロピオン酸、トリフルオロ酢酸、フマール酸、酒石酸、シュウ酸、マレイン酸、リンゴ酸、コハク酸、安息香酸、マンデル酸、アスコルビン酸、乳酸、グルコン酸、クエン酸等のカルボン酸の塩又はグルタミン酸、アスパラギン酸等のアミノ酸の塩とすることができる。 Among the compounds described in the present application, those which can be converted into acid addition salts according to a conventional method are, for example, hydrohalic acid salts such as hydrofluoric acid, hydrochloric acid, hydrobromic acid and hydroiodic acid, nitric acid , Inorganic acid salts such as sulfuric acid, phosphoric acid, chloric acid, perchloric acid, sulfonic acid salts such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid , Salt of carboxylic acid such as propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, citric acid or glutamic acid, It can be a salt of an amino acid such as aspartic acid.
　或いは、本願記載の化合物のうちで、常法に従って金属塩にすることができるものは、例えば、リチウム、ナトリウム、カリウムといったアルカリ金属の塩、カルシウム、バリウム、マグネシウムといったアルカリ土類金属の塩又はアルミニウムの塩とすることができる。 Alternatively, among the compounds described in the present application, those which can be converted into a metal salt according to a conventional method include, for example, alkali metal salts such as lithium, sodium and potassium, alkaline earth metal salts such as calcium, barium and magnesium, or aluminum The salt of
　或いは、本願記載の化合物のうちで、常法に従ってアミン塩にすることができるものは、例えば、アンモニア、メチルアミン、エチルアミン、プロピルアミン、ブチルアミン、ペンチルアミン、ベンジルアミン、アニリン、ジメチルアミン、ジエチルアミン、ジプロピルアミン、ジブチルアミン、ジペンチルアミン、ピロリジン、ピペリジン、ピペラジン、モルホリン、ジベンジルアミン、トリメチルアミン、トリエチルアミン、トリプロピルアミン、トリブチルアミン、トリペンチルアミン、トリベンジルアミンなどの塩とすることができる。 Alternatively, among the compounds described in the present application, those that can be converted into an amine salt according to a conventional method are, for example, ammonia, methylamine, ethylamine, propylamine, butylamine, pentylamine, benzylamine, aniline, dimethylamine, diethylamine, The salt may be a salt of dipropylamine, dibutylamine, dipentylamine, pyrrolidine, piperidine, piperazine, morpholine, dibenzylamine, trimethylamine, triethylamine, tripropylamine, tributylamine, tripentylamine, tribenzylamine and the like.
　次に、本明細書において示した各置換基の具体例を以下に示す。ここで、n-はノルマル、i-はイソ、s-はセカンダリー及びt-はターシャリーを各々意味し、Phはフェニルを意味する。 Next, specific examples of each substituent shown in the present specification are shown below. Here, n- represents normal, i- represents iso, s- represents secondary, and t- represents tertiary, and Ph represents phenyl.
　本願記載の化合物におけるハロゲン原子としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられる。尚、本明細書中「ハロ」の表記もこれらのハロゲン原子を表す。 Examples of the halogen atom in the compounds described in the present application include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. In the present specification, the notation “halo” also represents these halogen atoms.
　本明細書におけるＣa～Ｃbアルキルの表記は、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状の炭化水素基を表し、例えばメチル基、エチル基、ｎ－プロピル基、ｉ－プロピル基、ｎ－ブチル基、ｉ－ブチル基、ｓ－ブチル基、ｔ－ブチル基、ｎ－ペンチル基、１－メチルブチル基、２－メチルブチル基、３－メチルブチル基、１－エチルプロピル基、１，１－ジメチルプロピル基、１，２－ジメチルプロピル基、２，２－ジメチルプロピル基、ｎ－ヘキシル基、１－メチルペンチル基、２－メチルペンチル基、１，１－ジメチルブチル基、１，３－ジメチルブチル基、ヘプチル基、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b alkyl represents a linear or branched hydrocarbon group having a carbon number of a to b, such as a methyl group, an ethyl group, an n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 1,1-dimethylbutyl group, Specific examples include 1,3-dimethylbutyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group and the like, and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbシクロアルキルの表記は、炭素原子数がａ～ｂ個よりなる環状の炭化水素基を表し、３員環から６員環までの単環又は複合環構造を形成することが出来る。また、各々の環は指定の炭素原子数の範囲でアルキル基によって任意に置換されていてもよい。例えばシクロプロピル基、１－メチルシクロプロピル基、２－メチルシクロプロピル基、２，２－ジメチルシクロプロピル基、２，２，３，３－テトラメチルシクロプロピル基、シクロブチル基、シクロペンチル基、２－メチルシクロペンチル基、３－メチルシクロペンチル基、シクロヘキシル基、２－メチルシクロヘキシル基、３－メチルシクロヘキシル基、４－メチルシクロヘキシル基、ビシクロ［２．２．１］ヘプタン－２－イル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b cycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms, and forms a monocyclic or complex ring structure having 3 to 6 members. I can do it. Each ring may be optionally substituted with an alkyl group within the range of the specified number of carbon atoms. For example, cyclopropyl group, 1-methylcyclopropyl group, 2-methylcyclopropyl group, 2,2-dimethylcyclopropyl group, 2,2,3,3-tetramethylcyclopropyl group, cyclobutyl group, cyclopentyl group, 2- Specific examples include methylcyclopentyl group, 3-methylcyclopentyl group, cyclohexyl group, 2-methylcyclohexyl group, 3-methylcyclohexyl group, 4-methylcyclohexyl group, bicyclo [2.2.1] heptan-2-yl group, and the like. Each of which is selected for each specified number of carbon atoms.
　本明細書における芳香族基の表記としては、フェニル基、ナフチル基、アンスリル基等が具体例として挙げられる。 Specific examples of the notation of the aromatic group in the present specification include a phenyl group, a naphthyl group, an anthryl group, and the like.
　本明細書におけるＣa～Ｃbハロアルキルの表記は、炭素原子に結合した水素原子が、ハロゲン原子によって任意に置換された、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状の炭化水素基を表し、このとき、２個以上のハロゲン原子によって置換されている場合、それらのハロゲン原子は互いに同一でも、または互いに相異なっていてもよい。例えばフルオロメチル基、クロロメチル基、ブロモメチル基、ヨードメチル基、ジフルオロメチル基、クロロフルオロメチル基、ジクロロメチル基、ブロモフルオロメチル基、トリフルオロメチル基、クロロジフルオロメチル基、ジクロロフルオロメチル基、トリクロロメチル基、ブロモジフルオロメチル基、ブロモクロロフルオロメチル基、ジブロモフルオロメチル基、２－フルオロエチル基、２－クロロエチル基、２－ブロモエチル基、２，２－ジフルオロエチル基、２－クロロ－２－フルオロエチル基、２，２－ジクロロエチル基、２－ブロモ－２－フルオロエチル基、２，２，２－トリフルオロエチル基、２－クロロ－２，２－ジフルオロエチル基、２，２－ジクロロ－２－フルオロエチル基、２，２，２－トリクロロエチル基、２－ブロモ－２，２－ジフルオロエチル基、２－ブロモ－２－クロロ－２－フルオロエチル基、２－ブロモ－２，２－ジクロロエチル基、１，１，２，２－テトラフルオロエチル基、ペンタフルオロエチル基、１－クロロ－１，２，２，２－テトラフルオロエチル基、２－クロロ－１，１，２，２－テトラフルオロエチル基、１，２－ジクロロ－１，２，２－トリフルオロエチル基、２－ブロモ－１，１，２，２－テトラフルオロエチル基、２－フルオロプロピル基、２－クロロプロピル基、２－ブロモプロピル基、２－クロロ－２－フルオロプロピル基、２，３－ジクロロプロピル基、２－ブロモ－３－フルオロプロピル基、３－ブロモ－２－クロロプロピル基、２，３－ジブロモプロピル基、３，３，３－トリフルオロプロピル基、３－ブロモ－３，３－ジフルオロプロピル基、２，２，３，３－テトラフルオロプロピル基、２－クロロ－３，３，３－トリフルオロプロピル基、２，２，３，３，３－ペンタフルオロプロピル基、１，１，２，３，３，３－ヘキサフルオロプロピル基、ヘプタフルオロプロピル基、２，３－ジクロロ－１，１，２，３，３－ペンタフルオロプロピル基、２－フルオロ－１－メチルエチル基、２－クロロ－１－メチルエチル基、２－ブロモ－１－メチルエチル基、２，２，２－トリフルオロ－１－（トリフルオロメチル）エチル基、１，２，２，２－テトラフルオロ－１－（トリフルオロメチル）エチル基、２－フルオロブチル基、２－クロロブチル基、２，２，３，３，４，４－ヘキサフルオロブチル基、２，２，３，４，４，４－ヘキサフルオロブチル基、２，２，３，３，４，４－ヘキサフルオロブチル基、２，２，３，３，４，４，４－ヘプタフルオロブチル基、１，１，２，２，３，３，４，４－オクタフルオロブチル基、ノナフルオロブチル基、４－クロロ－１，１，２，２，３，３，４，４－オクタフルオロブチル基、２－フルオロ－２－メチルプロピル基、１，２，２，３，３，３－ヘキサフルオロ－１－（トリフルオロメチル）プロピル基、２－クロロ－１，１－ジメチルエチル基、２－ブロモ－１，１－ジメチルエチル基、５－クロロ－２，２，３，４，４，５，５－ヘプタフルオロペンチル基、トリデカフルオロヘキシル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkyl in the present specification is a linear or branched chain consisting of a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. Represents a hydrocarbon group, and when substituted by two or more halogen atoms, the halogen atoms may be the same as or different from each other. For example, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl Group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl Group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group, 2,2-dichloro-2 -Fluoroethyl group, 2,2,2-trichloroethyl group, 2 Bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 2-bromo-2,2-dichloroethyl group, 1,1,2,2-tetrafluoroethyl group, penta Fluoroethyl group, 1-chloro-1,2,2,2-tetrafluoroethyl group, 2-chloro-1,1,2,2-tetrafluoroethyl group, 1,2-dichloro-1,2,2- Trifluoroethyl group, 2-bromo-1,1,2,2-tetrafluoroethyl group, 2-fluoropropyl group, 2-chloropropyl group, 2-bromopropyl group, 2-chloro-2-fluoropropyl group, 2,3-dichloropropyl group, 2-bromo-3-fluoropropyl group, 3-bromo-2-chloropropyl group, 2,3-dibromopropyl group, 3,3,3-trifluoropropyl group, 3-butyl Mo-3,3-difluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2-chloro-3,3,3-trifluoropropyl group, 2,2,3,3,3-pentafluoro Propyl group, 1,1,2,3,3,3-hexafluoropropyl group, heptafluoropropyl group, 2,3-dichloro-1,1,2,3,3-pentafluoropropyl group, 2-fluoro- 1-methylethyl group, 2-chloro-1-methylethyl group, 2-bromo-1-methylethyl group, 2,2,2-trifluoro-1- (trifluoromethyl) ethyl group, 1,2,2 , 2-tetrafluoro-1- (trifluoromethyl) ethyl group, 2-fluorobutyl group, 2-chlorobutyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3, 4,4,4-hexafluoro Butyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3,3,4,4,4-heptafluorobutyl group, 1,1,2,2,3,3 , 4,4-octafluorobutyl group, nonafluorobutyl group, 4-chloro-1,1,2,2,3,3,4,4-octafluorobutyl group, 2-fluoro-2-methylpropyl group, 1,2,2,3,3,3-hexafluoro-1- (trifluoromethyl) propyl group, 2-chloro-1,1-dimethylethyl group, 2-bromo-1,1-dimethylethyl group, 5 Specific examples include -chloro-2,2,3,4,4,5,5-heptafluoropentyl group, tridecafluorohexyl group and the like, and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるシアノ（Ｃa～Ｃb）アルキルの表記は、炭素原子に結合した水素原子が、シアノ基によって任意に置換された、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状のアルキル基を表し、例えばシアノメチル基、１－シアノエチル基、２－シアノエチル基、２－シアノプロピル基、３－シアノプロピル基、２－シアノブチル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of cyano (C a -C b ) alkyl in the present specification is a straight or branched chain consisting of a to b carbon atoms, in which a hydrogen atom bonded to a carbon atom is optionally substituted with a cyano group Represents a chain alkyl group, for example, cyanomethyl group, 1-cyanoethyl group, 2-cyanoethyl group, 2-cyanopropyl group, 3-cyanopropyl group, 2-cyanobutyl group and the like. Selected in the range of the number of carbon atoms.
　本明細書におけるＣa～Ｃbハロシクロアルキルの表記は、炭素原子に結合した水素原子が、ハロゲン原子によって任意に置換された、炭素原子数がａ～ｂ個よりなる環状の炭化水素基を表し、３員環から６員環までの単環又は複合環構造を形成することが出来る。また、各々の環は指定の炭素原子数の範囲でアルキル基によって任意に置換されていてもよく、ハロゲン原子による置換は環構造部分であっても、側鎖部分であっても、或いはそれらの両方であってもよく、さらに、２個以上のハロゲン原子によって置換されている場合、それらのハロゲン原子は互いに同一でも、または互いに相異なっていてもよい。例えば２，２－ジフルオロシクロプロピル基、２，２－ジクロロシクロプロピル基、２，２－ジブロモシクロプロピル基、２，２－ジフルオロ－１－メチルシクロプロピル基、２，２－ジクロロ－１－メチルシクロプロピル基、２，２－ジブロモ－１－メチルシクロプロピル基、２，２，３，３－テトラフルオロシクロブチル基、２－（トリフルオロメチル）シクロヘキシル基、３－（トリフルオロメチル）シクロヘキシル基、４－（トリフルオロメチル）シクロヘキシル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b halocycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. And can form monocyclic or complex ring structures from 3 to 6-membered rings. Each ring may be optionally substituted with an alkyl group within the range of the specified number of carbon atoms, and the substitution with a halogen atom may be a ring structure part, a side chain part, They may be both, and when they are substituted by two or more halogen atoms, the halogen atoms may be the same as or different from each other. For example, 2,2-difluorocyclopropyl group, 2,2-dichlorocyclopropyl group, 2,2-dibromocyclopropyl group, 2,2-difluoro-1-methylcyclopropyl group, 2,2-dichloro-1-methyl Cyclopropyl group, 2,2-dibromo-1-methylcyclopropyl group, 2,2,3,3-tetrafluorocyclobutyl group, 2- (trifluoromethyl) cyclohexyl group, 3- (trifluoromethyl) cyclohexyl group , 4- (trifluoromethyl) cyclohexyl group and the like are listed as specific examples, and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbアルケニルの表記は、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状で、且つ分子内に１個又は２個以上の二重結合を有する不飽和炭化水素基を表し、例えばビニル基、１－プロペニル基、２－プロペニル基、１－メチルエテニル基、２－ブテニル基、１－メチル－２－プロペニル基、２－メチル－２－プロペニル基、２－ペンテニル基、２－メチル－２－ブテニル基、３－メチル－２－ブテニル基、２－エチル－２－プロペニル基、１，１－ジメチル－２－プロペニル基、２－ヘキセニル基、２－メチル－２－ペンテニル基、２，４－ジメチル－２，６－ヘプタジエニル基、３，７－ジメチル－２，６－オクタジエニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b alkenyl is a linear or branched chain composed of a to b carbon atoms and has one or more double bonds in the molecule. Represents a saturated hydrocarbon group, such as a vinyl group, 1-propenyl group, 2-propenyl group, 1-methylethenyl group, 2-butenyl group, 1-methyl-2-propenyl group, 2-methyl-2-propenyl group, 2 -Pentenyl group, 2-methyl-2-butenyl group, 3-methyl-2-butenyl group, 2-ethyl-2-propenyl group, 1,1-dimethyl-2-propenyl group, 2-hexenyl group, 2-methyl Specific examples include -2-pentenyl group, 2,4-dimethyl-2,6-heptadienyl group, 3,7-dimethyl-2,6-octadienyl group, etc., selected within the range of each designated number of carbon atoms. Is done.
　本明細書におけるＣa～Ｃbハロアルケニルの表記は、炭素原子に結合した水素原子が、ハロゲン原子によって任意に置換された、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状で、且つ分子内に１個又は２個以上の二重結合を有する不飽和炭化水素基を表す。このとき、２個以上のハロゲン原子によって置換されている場合、それらのハロゲン原子は互いに同一でも、または互いに相異なっていてもよい。例えば２，２－ジクロロビニル基、２－フルオロ－２－プロペニル基、２－クロロ－２－プロペニル基、３－クロロ－２－プロペニル基、２－ブロモ－２－プロペニル基、３－ブロモ－２－プロペニル基、３，３－ジフルオロ－２－プロペニル基、２，３－ジクロロ－２－プロペニル基、３，３－ジクロロ－２－プロペニル基、２，３－ジブロモ－２－プロペニル基、２，３，３－トリフルオロ－２－プロペニル基、２，３，３－トリクロロ－２－プロペニル基、１－（トリフルオロメチル）エテニル基、３－クロロ－２－ブテニル基、３－ブロモ－２－ブテニル基、４，４－ジフルオロ－３－ブテニル基、３，４，４－トリフルオロ－３－ブテニル基、３－クロロ－４，４，４－トリフルオロ－２－ブテニル基、３－ブロモ－２－メチル－２－プロペニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b haloalkenyl is a linear or branched chain having a carbon number of a to b, wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. And an unsaturated hydrocarbon group having one or more double bonds in the molecule. At this time, when substituted with two or more halogen atoms, the halogen atoms may be the same as or different from each other. For example, 2,2-dichlorovinyl group, 2-fluoro-2-propenyl group, 2-chloro-2-propenyl group, 3-chloro-2-propenyl group, 2-bromo-2-propenyl group, 3-bromo-2 -Propenyl group, 3,3-difluoro-2-propenyl group, 2,3-dichloro-2-propenyl group, 3,3-dichloro-2-propenyl group, 2,3-dibromo-2-propenyl group, 2, 3,3-trifluoro-2-propenyl group, 2,3,3-trichloro-2-propenyl group, 1- (trifluoromethyl) ethenyl group, 3-chloro-2-butenyl group, 3-bromo-2- Butenyl group, 4,4-difluoro-3-butenyl group, 3,4,4-trifluoro-3-butenyl group, 3-chloro-4,4,4-trifluoro-2-butenyl group, 3-bromo- 2-methyl- - propenyl group, etc. As a specific example, it may be selected from the range of the specified number of carbon atoms.
　本明細書におけるＣa～Ｃbアルキニルの表記は、炭素原子数がａ～ｂ個よりなる直鎖状又は分岐鎖状で、且つ分子内に１個又は２個以上の三重結合を有する不飽和炭化水素基を表し、例えばエチニル基、１－プロピニル基、２－プロピニル基、２－ブチニル基、１－メチル－２－プロピニル基、２－ペンチニル基、１－メチル－２－ブチニル基、１，１－ジメチル－２－プロピニル基、２－ヘキシニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b alkynyl represents a linear or branched chain having a carbon number of a to b and an unsaturated group having one or more triple bonds in the molecule. Represents a hydrocarbon group, for example, ethynyl group, 1-propynyl group, 2-propynyl group, 2-butynyl group, 1-methyl-2-propynyl group, 2-pentynyl group, 1-methyl-2-butynyl group, 1, Specific examples include a 1-dimethyl-2-propynyl group, a 2-hexynyl group, and the like, and each is selected within the specified number of carbon atoms.
　本明細書におけるＣa～Ｃbアルコキシの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｏ－基を表し、例えばメトキシ基、エトキシ基、ｎ－プロピルオキシ基、ｉ－プロピルオキシ基、ｎ－ブチルオキシ基、ｉ－ブチルオキシ基、ｓ－ブチルオキシ基、ｔ－ブチルオキシ基、ｎ－ペンチルオキシ基、ｎ－ヘキシルオキシ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkoxy in the present specification represents an alkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, a methoxy group, an ethoxy group, an n-propyloxy group, Specific examples include i-propyloxy group, n-butyloxy group, i-butyloxy group, s-butyloxy group, t-butyloxy group, n-pentyloxy group, n-hexyloxy group and the like. It is selected in the range of the number of atoms.
　本明細書におけるＣa～Ｃbハロアルコキシの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるハロアルキル－Ｏ－基を表し、例えばジフルオロメトキシ基、トリフルオロメトキシ基、クロロジフルオロメトキシ基、ブロモジフルオロメトキシ基、２－フルオロエトキシ基、２－クロロエトキシ基、２，２，２－トリフルオロエトキシ基、１，１，２，２，－テトラフルオロエトキシ基、２－クロロ－１，１，２－トリフルオロエトキシ基、２－ブロモ－１，１，２－トリフルオロエトキシ基、ペンタフルオロエトキシ基、２，２－ジクロロ－１，１，２－トリフルオロエトキシ基、２，２，２－トリクロロ－１，１－ジフルオロエトキシ基、２－ブロモ－１，１，２，２－テトラフルオロエトキシ基、２，２，３，３－テトラフルオロプロピルオキシ基、１，１，２，３，３，３－ヘキサフルオロプロピルオキシ基、２，２，２－トリフルオロ－１－（トリフルオロメチル）エトキシ基、ヘプタフルオロプロピルオキシ基、２－ブロモ－１，１，２，３，３，３－ヘキサフルオロプロピルオキシ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkoxy in the present specification represents a haloalkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethoxy group, trifluoromethoxy group, chlorodifluoro Methoxy group, bromodifluoromethoxy group, 2-fluoroethoxy group, 2-chloroethoxy group, 2,2,2-trifluoroethoxy group, 1,1,2,2, -tetrafluoroethoxy group, 2-chloro-1 , 1,2-trifluoroethoxy group, 2-bromo-1,1,2-trifluoroethoxy group, pentafluoroethoxy group, 2,2-dichloro-1,1,2-trifluoroethoxy group, 2,2 , 2-trichloro-1,1-difluoroethoxy group, 2-bromo-1,1,2,2-tetrafluoroethoxy group, 2,2,3,3-tetrafur Ropropyloxy group, 1,1,2,3,3,3-hexafluoropropyloxy group, 2,2,2-trifluoro-1- (trifluoromethyl) ethoxy group, heptafluoropropyloxy group, 2- Specific examples include a bromo-1,1,2,3,3,3-hexafluoropropyloxy group and the like, which are selected in the range of the respective designated number of carbon atoms.
　本明細書におけるＣa～Ｃbアルキルスルホニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－ＳＯ2－基を表し、例えばメチルスルホニル基、エチルスルホニル基、ｎ－プロピルスルホニル基、ｉ－プロピルスルホニル基、ｎ－ブチルスルホニル基、ｉ－ブチルスルホニル基、ｓ－ブチルスルホニル基、ｔ－ブチルスルホニル基、ｎ－ペンチルスルホニル基、ｎ－ヘキシルスルホニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylsulfonyl in the present specification represents an alkyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylsulfonyl group, ethylsulfonyl group, n- Specific examples include propylsulfonyl group, i-propylsulfonyl group, n-butylsulfonyl group, i-butylsulfonyl group, s-butylsulfonyl group, t-butylsulfonyl group, n-pentylsulfonyl group, n-hexylsulfonyl group and the like. Each of which is selected for each specified number of carbon atoms.
　本明細書におけるＣa～Ｃbハロアルキルスルホニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるハロアルキル－ＳＯ2－基を表し、例えばジフルオロメチルスルホニル基、トリフルオロメチルスルホニル基、クロロジフルオロメチルスルホニル基、ブロモジフルオロメチルスルホニル基、２，２，２－トリフルオロエチルスルホニル基、１，１，２，２－テトラフルオロエチルスルホニル基、２－クロロ－１，１，２－トリフルオロエチルスルホニル基、２－ブロモ－１，１，２，２－テトラフルオロエチルスルホニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkylsulfonyl in the present specification represents a haloalkyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethylsulfonyl group, trifluoromethylsulfonyl group Chlorodifluoromethylsulfonyl group, bromodifluoromethylsulfonyl group, 2,2,2-trifluoroethylsulfonyl group, 1,1,2,2-tetrafluoroethylsulfonyl group, 2-chloro-1,1,2-trimethyl Specific examples include a fluoroethylsulfonyl group, a 2-bromo-1,1,2,2-tetrafluoroethylsulfonyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbアルキルカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｃ（Ｏ）－基を表し、例えばアセチル基、プロピオニル基、ブチリル基、イソブチリル基、バレリル基、イソバレリル基、２－メチルブタノイル基、ピバロイル基、ヘキサノイル基、ヘプタノイル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylcarbonyl in the present specification represents an alkyl-C (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group. Specific examples thereof include isobutyryl group, valeryl group, isovaleryl group, 2-methylbutanoyl group, pivaloyl group, hexanoyl group, heptanoyl group and the like, and each is selected in the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbハロアルキルカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるハロアルキル－Ｃ（Ｏ）－基を表し、例えばフルオロアセチル基、クロロアセチル基、ジフルオロアセチル基、ジクロロアセチル基、トリフルオロアセチル基、クロロジフルオロアセチル基、ブロモジフルオロアセチル基、トリクロロアセチル基、ペンタフルオロプロピオニル基、ヘプタフルオロブタノイル基、３－クロロ－２，２－ジメチルプロパノイル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkylcarbonyl in the present specification represents a haloalkyl-C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, such as a fluoroacetyl group, a chloroacetyl group, Difluoroacetyl group, dichloroacetyl group, trifluoroacetyl group, chlorodifluoroacetyl group, bromodifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, heptafluorobutanoyl group, 3-chloro-2,2-dimethylpropanoyl group Etc. are given as specific examples, and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbアルコキシカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｏ－Ｃ（Ｏ）－基を表し、例えばメトキシカルボニル基、エトキシカルボニル基、　ｎ－プロピルオキシカルボニル基、ｉ－プロピルオキシカルボニル基、ｎ－ブトキシカルボニル基、ｉ－ブトキシカルボニル基、ｔ－ブトキシカルボニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b alkoxycarbonyl represents an alkyl-O—C (O) — group having the above-mentioned meanings consisting of a to b carbon atoms, for example, methoxycarbonyl group, ethoxycarbonyl Specific examples include a group, n-propyloxycarbonyl group, i-propyloxycarbonyl group, n-butoxycarbonyl group, i-butoxycarbonyl group, t-butoxycarbonyl group, etc. Selected.
　本明細書におけるＣa～Ｃbアルキルチオカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｓ－Ｃ（Ｏ）－基を表し、例えばメチルチオ－Ｃ（Ｏ）－基、エチルチオ－Ｃ（Ｏ）－基、ｎ－プロピルチオ－Ｃ（Ｏ）－基、ｉ－プロピルチオ－Ｃ（Ｏ）－基、ｎ－ブチルチオ－Ｃ（Ｏ）－基、ｉ－ブチルチオ－Ｃ（Ｏ）－基、ｔ－ブチルチオ－Ｃ（Ｏ）－基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, the expression C a -C b alkylthiocarbonyl represents an alkyl-S—C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (O) -Group, ethylthio-C (O)-group, n-propylthio-C (O)-group, i-propylthio-C (O)-group, n-butylthio-C (O)-group, i-butylthio-C Specific examples include (O) -group, t-butylthio-C (O) -group, etc., and each is selected within the range of the designated number of carbon atoms.
　本明細書におけるＣa～Ｃbアルコキシチオカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｏ－Ｃ（Ｓ）－基を表し、例えばメトキシ－Ｃ（Ｓ）－基、エトキシ－Ｃ（Ｓ）－基、ｎ－プロピルオキシ－Ｃ（Ｓ）－基、ｉ－プロピルオキシ－Ｃ（Ｓ）－基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, the expression C a -C b alkoxythiocarbonyl represents an alkyl-O—C (S) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methoxy-C (S ) -Group, ethoxy-C (S) -group, n-propyloxy-C (S) -group, i-propyloxy-C (S) -group, etc. Selected in a range of numbers.
　本明細書におけるＣa～Ｃbアルキルジチオカルボニルの表記は、炭素原子数がａ～ｂ個よりなる前記の意味であるアルキル－Ｓ－Ｃ（Ｓ）－基を表し、例えばメチルチオ－Ｃ（Ｓ）－基、エチルチオ－Ｃ（Ｓ）－基、ｎ－プロピルチオ－Ｃ（Ｓ）－基、ｉ－プロピルチオ－Ｃ（Ｓ）－基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, the expression C a -C b alkyldithiocarbonyl represents an alkyl-S—C (S) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (S ) -Group, ethylthio-C (S) -group, n-propylthio-C (S) -group, i-propylthio-C (S) -group and the like. Selected by range.
　本明細書におけるＣa～Ｃbアルコキシ（Ｃd～Ｃe）アルキル、ヒドロキシ（Ｃd～Ｃe）ハロアルキル、Ｃa～Ｃbアルコキシ（Ｃd～Ｃe）ハロアルキル又はＣa～Ｃbハロアルコキシ（Ｃd～Ｃe）ハロアルキル等の表記は、それぞれ前記の意味である任意のＣa～Ｃbアルコキシ基、Ｃa～Ｃbハロアルコキシ基又は水酸基によって炭素原子に結合した水素原子又はハロゲン原子が任意に置換された炭素原子数がｄ～ｅ個よりなる前記の意味であるハロアルキル基を表し、例えば２，２，２－トリフルオロ－１－ヒドロキシ－１－（トリフルオロメチル）エチル基、ジフルオロ（メトキシ）メチル基、２，２，２－トリフルオロ－１－メトキシ－１－（トリフルオロメチル）エチル基、ジフルオロ（２，２，２－トリフルオロエトキシ）メチル基、２，２，２－トリフルオロ－１－（２，２，２－トリフルオロエトキシ）－１－（トリフルオロメチル）エチル基、３－（１，２－ジクロロ－１，２，２－トリフルオロエトキシ）－１，１，２，２，３，３－ヘキサフルオロプロピル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 C a -C b alkoxy (C d -C e ) alkyl, hydroxy (C d -C e ) haloalkyl, C a -C b alkoxy (C d -C e ) haloalkyl or C a -C b halo herein The notation such as alkoxy (C d -C e ) haloalkyl represents a hydrogen atom or halogen bonded to a carbon atom by any C a -C b alkoxy group, C a -C b haloalkoxy group or hydroxyl group, respectively, as defined above. Represents a haloalkyl group having the above meaning consisting of d to e optionally substituted carbon atoms, for example 2,2,2-trifluoro-1-hydroxy-1- (trifluoromethyl) ethyl group Difluoro (methoxy) methyl group, 2,2,2-trifluoro-1-methoxy-1- (trifluoromethyl) ethyl group, difluoro (2,2,2-trifluoroethoxy) ) Methyl group, 2,2,2-trifluoro-1- (2,2,2-trifluoroethoxy) -1- (trifluoromethyl) ethyl group, 3- (1,2-dichloro-1,2, Specific examples include 2-trifluoroethoxy) -1,1,2,2,3,3-hexafluoropropyl group and the like, and each is selected within the range of the designated number of carbon atoms.
　本願記載の化合物において、Ｘで表される置換基としては、好ましくはハロゲン原子、シアノ、ニトロ、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6ハロアルキル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、シアノ（Ｃ1～Ｃ6）アルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル、－ＯＨ、－ＯＲ5、－ＮＨ2及び－Ｎ（Ｒ7）Ｒ6が挙げられ、より好ましくはフッ素原子、塩素原子、臭素原子、ヨウ素原子、シアノ、メチル、トリフルオロメチル、ペンタフルオロエチル、トリフルオロメトキシ、ジフルオロメトキシ、ブロモジフルオロメトキシ、トリフルオロメチルチオ、クロロジフルオロメチルチオ及びブロモジフルオロメチルチオが挙げられる。このときＸで表される置換基の数を表すｍが２以上の整数を表すとき、各々のＸは互いに同一であっても又は互いに相異なっていてもよい。
　本願記載の化合物において、Ｘで表される置換基の数を表すｍとしては、好ましくは１、２及び３が挙げられる。
　本願記載の化合物において、Ｘで表される置換基の位置としては、より好ましくはＲ1が結合する炭素との結合位置に対して、メタ位及びパラ位が挙げられる。 In the compounds described in the present application, the substituent represented by X is preferably a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl,- OH, —OR 5 , —NH 2 and —N (R 7 ) R 6 , more preferably fluorine atom, chlorine atom, bromine atom, iodine atom, cyano, methyl, trifluoromethyl, pentafluoroethyl, tri Fluoromethoxy, difluoromethoxy, bromodifluoromethoxy, trifluoromethylthio, chlorodifluoromethylthio and bromodifluoromethylthio At this time, when m representing the number of substituents represented by X represents an integer of 2 or more, each X may be the same as or different from each other.
In the compounds described in the present application, m representing the number of substituents represented by X preferably includes 1, 2 and 3.
In the compounds described in the present application, the position of the substituent represented by X preferably includes a meta position and a para position with respect to the bonding position with the carbon to which R 1 is bonded.
　本願記載の化合物において、Ｒ1で表される置換基としては、好ましくはＣ1～Ｃ4ハロアルキルが挙げられ、より好ましくはジフルオロメチル、クロロジフルオロメチル、ブロモジフルオロメチル及びトリフルオロメチルが挙げられ、極めて好ましくはクロロジフルオロメチル及びトリフルオロメチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 1 preferably includes C 1 -C 4 haloalkyl, more preferably difluoromethyl, chlorodifluoromethyl, bromodifluoromethyl, and trifluoromethyl. Very particular preference is given to chlorodifluoromethyl and trifluoromethyl.
　本願記載の化合物において、Ｒ2で表される置換基としては、好ましくはメチル、エチル、ｎ‐プロピル、ｉ‐プロピル、ｎ‐ブチル、ｉ‐ブチル、ｔ‐ブチル又はフェニルが挙げられ、より好ましくはメチル、エチル及びｔ‐ブチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 2 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
　本願記載の化合物において、Ｒ3で表される置換基としては、好ましくはメチル、エチル、ｎ‐プロピル、ｉ‐プロピル、ｎ‐ブチル、ｉ‐ブチル、ｔ‐ブチル又はフェニルが挙げられ、より好ましくはメチル、エチル及びｔ‐ブチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 3 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
　本願記載の化合物において、Ｒ4で表される置換基としては、好ましくはメチル、エチル、ｎ‐プロピル、ｉ‐プロピル、ｎ‐ブチル、ｉ‐ブチル、ｔ‐ブチル又はフェニルが挙げられ、より好ましくはメチル、エチル及びｔ‐ブチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 4 is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or phenyl, more preferably Includes methyl, ethyl and t-butyl.
　本願記載の化合物において、Ｒ5で表される置換基としては、好ましくはＣ1～Ｃ6ハロアルキル及びＣ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキルが挙げられ、より好ましくはトリフルオロメチル、ジフルオロメチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 5 preferably includes C 1 -C 6 haloalkyl and C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, more preferably trifluoro Examples thereof include methyl and difluoromethyl.
　本願記載の化合物において、Ｒ6で表される置換基としては、好ましくはＣ1～Ｃ6アルキル、Ｃ1～Ｃ6アルキルカルボニル、Ｃ1～Ｃ6ハロアルキルカルボニル及びＣ1～Ｃ6アルコキシカルボニルが挙げられ、より好ましくは、メチル、アセチル、プロピオニル、トリフルオロアセチル、メトキシカルボニル及びエトキシカルボニルが挙げられる。 In the compounds described in the present application, the substituent represented by R 6 is preferably C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl and C 1 -C 6 alkoxycarbonyl. More preferred are methyl, acetyl, propionyl, trifluoroacetyl, methoxycarbonyl and ethoxycarbonyl.
　本願記載の化合物において、Ｒ7で表される置換基としては、好ましくは水素原子及びメチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 7 preferably includes a hydrogen atom and methyl.
　本願記載の化合物において、Ｒ8で表される置換基としては、好ましくはＣ1～Ｃ4アルキルが挙げられ、より好ましくはメチル、エチル、ｎ‐プロピル、ｉ‐プロピル、ｎ‐ブチル、ｉ‐ブチル、ｔ‐ブチル又はフェニルが挙げられ、極めて好ましくはメチル及びエチルが挙げられる。 In the compounds described in the present application, the substituent represented by R 8 preferably includes C 1 -C 4 alkyl, and more preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, i- Examples include butyl, t-butyl or phenyl, and very preferably methyl and ethyl.
　本願記載の化合物において、硫黄原子上の酸素の数を表すｒとしては、０、１及び２が挙げられる。 In the compounds described in this application, examples of r representing the number of oxygen atoms on the sulfur atom include 0, 1, and 2.
　本発明の反応に使用できる溶媒としては、反応に不活性であれば特に制限はないが、例えば、ベンゼン、トルエン、キシレン、クロロベンゼン、ｏ‐ジクロロベンゼン又はメシチレン等のハロゲン原子で置換されてもよい芳香族炭化水素類、若しくはｎ‐ペンタン、ｎ‐ヘキサン、ｎ‐ヘプタン、ｎ‐オクタン、シクロペンタン、シクロヘキサン、メチルシクロヘキサン、塩化メチレン又は１，２‐ジクロロエタン等のハロゲン原子で置換されてもよい脂肪族炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、シクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル、ジメトキシエタン等のエーテル類、アセトニトリル、プロピオニトリル等のニトリル類、酢酸エチル、酢酸ブチル等のエステル類、メタノール、エタノール等のアルコール類、トリエチルアミン、トリブチルアミン、ピリジン等のアミン類、ニトロメタン、ニトロエタン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシド、水、超臨界流体等が挙げられ、好ましくはトルエン、クロロベンゼン、ｎ‐ヘキサン、ｎ‐ヘプタン、シクロヘキサン、塩化メチレン、１，２‐ジクロロエタン、ジイソプロピルエーテル、シクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル、ジメトキシエタン、アセトニトリル、プロピオニトリル、酢酸エチル、メタノール、ニトロメタン、Ｎ，Ｎ‐ジメチルホルムアミド又はジメチルスルホキシドであり、特に好ましくは（１）からの（２）の製造についてはトルエンであり、（３）からの（１）の製造についてはトルエン、メタノール、Ｎ，Ｎ‐ジメチルホルムアミド又はジメチルスルホキシドであり、（４）と（５）とから（３）を製造する場合についてはトルエン、Ｎ，Ｎ‐ジメチルホルムアミド又はジメチルスルホキシドであり、（４）と（５）とから１工程で（１）を製造する場合についてはトルエン、メタノール、Ｎ，Ｎ‐ジメチルホルムアミド又はジメチルスルホキシドである。これらは単独で使用しても良いし、２種以上を混合して使用しても良く、（１２）と（５）とからの（１３）の製造についてはトルエン、クロロベンゼン、ｎ‐ヘキサン、ｎ‐ヘプタン、シクロヘキサン、シクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル又はジメトキシエタンであり、（１３）からの（２）の製造についてはトルエン、クロロベンゼン、ｎ‐ヘキサン、ｎ‐ヘプタン、シクロヘキサン、シクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル、ジメトキシエタン、アセトニトリル、メタノール又はエタノールであり、（１２）と（５）とから１工程で（２）を製造する場合についてはトルエン、クロロベンゼン、ｎ‐ヘキサン、ｎ‐ヘプタン、シクロヘキサン、シクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル、ジメトキシエタン、アセトニトリル、メタノール又はエタノールである。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。例えば、トルエンとシクロペンチルメチルエーテル、ｔ‐ブチルメチルエーテル又はジメトキシエタンとの混合溶媒などが、－７８℃のような極低温反応を避けるという点から好ましい。 The solvent that can be used in the reaction of the present invention is not particularly limited as long as it is inert to the reaction. For example, it may be substituted with a halogen atom such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, or mesitylene. Aromatic hydrocarbons or fats that may be substituted with halogen atoms such as n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylcyclohexane, methylene chloride or 1,2-dichloroethane Aromatic hydrocarbons, diethyl ether, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, ethers such as dimethoxyethane, nitriles such as acetonitrile and propionitrile, esters such as ethyl acetate and butyl acetate, methanol, Ethanol etc. Examples include alcohols, amines such as triethylamine, tributylamine, pyridine, nitromethane, nitroethane, N, N-dimethylformamide, dimethyl sulfoxide, water, supercritical fluid, etc., preferably toluene, chlorobenzene, n-hexane, n- Heptane, cyclohexane, methylene chloride, 1,2-dichloroethane, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, dimethoxyethane, acetonitrile, propionitrile, ethyl acetate, methanol, nitromethane, N, N-dimethylformamide or dimethyl Sulfoxide, particularly preferably toluene for the production of (2) from (1), toluene, methanol, N, N-dimethyl for the production of (1) from (3) In the case where (3) is produced from (4) and (5), it is toluene, N, N-dimethylformamide or dimethyl sulfoxide, and is one step from (4) and (5). In the case of producing (1), toluene, methanol, N, N-dimethylformamide or dimethyl sulfoxide. These may be used singly or as a mixture of two or more. For the production of (13) from (12) and (5), toluene, chlorobenzene, n-hexane, n -Heptane, cyclohexane, cyclopentyl methyl ether, t-butyl methyl ether or dimethoxyethane. For the preparation of (2) from (13), toluene, chlorobenzene, n-hexane, n-heptane, cyclohexane, cyclopentyl methyl ether, t-butyl methyl ether, dimethoxyethane, acetonitrile, methanol or ethanol, and when (2) is produced from (12) and (5) in one step, toluene, chlorobenzene, n-hexane, n-heptane, Cyclohexane, cyclopentyl methyl ether, t-butyl Ether, dimethoxyethane, acetonitrile, methanol or ethanol. These may be used singly or in combination of two or more. For example, a mixed solvent of toluene and cyclopentyl methyl ether, t-butyl methyl ether, or dimethoxyethane is preferable from the viewpoint of avoiding a cryogenic reaction such as −78 ° C.
　斯かる溶媒の使用量は特に限定されないが、芳香族ケトン化合物又は置換シリルエーテル化合物、１－（置換フェニル）－１－置換アルコール化合物又は芳香族エステル化合物に対して、通常０．０１～５０重量部、好ましくは０．０５～２５重量部、特に好ましくは０．１～１０重量部である。 The amount of such a solvent to be used is not particularly limited, but is usually 0.01 to 50% by weight with respect to the aromatic ketone compound, substituted silyl ether compound, 1- (substituted phenyl) -1-substituted alcohol compound or aromatic ester compound. Parts, preferably 0.05 to 25 parts by weight, particularly preferably 0.1 to 10 parts by weight.

　本発明の反応に使用できる触媒としては、例えば、水酸化ナトリウム、水酸化カリウム、水酸化バリウム、水酸化カルシウム、炭酸カリウム、炭酸ナトリウム、炭酸バリウム、炭酸カルシウム、炭酸水素カリウム、炭酸水素ナトリウム、酢酸ナトリウム、酢酸カリウム、酢酸リチウム、燐酸カリウム、燐酸水素ジカリウム、燐酸二水素カリウム、ナトリウムメトキシド、カリウム‐ｔ‐ブトキシド、シンコニジン、トリメチルアミン‐Ｎ‐オキシド、トリ‐ｔ‐ブチルホスフィン、トリ‐ｎ‐ブチルホスフィン、テトラ‐ｎ‐ブチルアンモニウムクロリド、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウム、硫酸水素　テトラ‐ｎ‐ブチルアンモニウム、塩酸、臭化水素酸、硫酸、硝酸、燐酸、ｐ－トルエンスルホン酸、蟻酸又は酢酸が挙げられ、好ましくは炭酸カリウム、炭酸ナトリウム、酢酸ナトリウム、酢酸カリウム、酢酸リチウム、燐酸カリウム、燐酸水素ジカリウム、燐酸二水素カリウム、テトラ‐ｎ‐ブチルアンモニウムクロリド、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウム、塩酸、硫酸又は酢酸である。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。
Examples of the catalyst that can be used in the reaction of the present invention include sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, potassium carbonate, sodium carbonate, barium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, acetic acid. Sodium, potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium methoxide, potassium tert-butoxide, cinchonidine, trimethylamine-N-oxide, tri-t-butylphosphine, tri-n-butyl Phosphine, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, acetic acid tetra-n-butylammonium, hydrogen sulfate tetra-n-butylammonium, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, p- toluene Examples include sulfonic acid, formic acid or acetic acid, preferably potassium carbonate, sodium carbonate, sodium acetate, potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, tetra-n-butylammonium chloride, tetra-n. -Butylammonium bromide, acetic acid tetra-n-butylammonium, hydrochloric acid, sulfuric acid or acetic acid. These may be used singly or in combination of two or more.
　斯かる触媒の使用量は特に限定されないが、例えば、（３）からの（１）の製造の場合のように、加水分解触媒として使用する場合については置換シリルエーテル化合物１重量部に対して、通常０．１～１０重量部であり、例えば、（４）と（５）とからの（３）の製造の場合のように、付加反応触媒として使用する場合については芳香族アルデヒド化合物１モルに対して、通常０．００１～１倍モル、好ましくは０．００５～０．５倍モル、特に好ましくは０．００５～０．１倍モルである。 The amount of such a catalyst used is not particularly limited. For example, when used as a hydrolysis catalyst as in the production of (1) from (3), with respect to 1 part by weight of the substituted silyl ether compound, The amount is usually 0.1 to 10 parts by weight. For example, in the case of using as an addition reaction catalyst as in the production of (3) from (4) and (5), 1 mol of the aromatic aldehyde compound is used. On the other hand, it is usually 0.001 to 1 times mol, preferably 0.005 to 0.5 times mol, particularly preferably 0.005 to 0.1 times mol.
　本発明の反応に使用できる酸化触媒としては、例えば、２，２，６，６‐テトラメチルピペリジン‐１‐オキシル、４‐ヒドロキシ‐２，２，６，６‐テトラメチルピペリジン‐１‐オキシル、４‐メトキシ‐２，２，６，６‐テトラメチルピペリジン‐１‐オキシル、４‐アセタミド‐２，２，６，６‐テトラメチルピペリジン‐１‐オキシル、２‐アザアダマンタン‐Ｎ‐オキシル、１‐メチル‐２‐アザアダマンタン‐Ｎ‐オキシル、１，３‐ジメチル‐２‐アザアダマンタン‐Ｎ‐オキシル等が挙げられ、好ましくは、例えば２，２，６，６‐テトラメチルピペリジン‐１‐オキシル、２‐アザアダマンタン‐Ｎ‐オキシルである。 Examples of the oxidation catalyst that can be used in the reaction of the present invention include 2,2,6,6-tetramethylpiperidine-1-oxyl, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl, 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 2-azaadamantane-N-oxyl, 1 -Methyl-2-azaadamantane-N-oxyl, 1,3-dimethyl-2-azaadamantane-N-oxyl and the like, and preferably 2,2,6,6-tetramethylpiperidine-1-oxyl, for example 2-azaadamantane-N-oxyl.
　斯かる酸化触媒の使用量は特に限定されないが、１－（置換フェニル）－１－置換アルコール化合物１モルまたは１重量部に対して、通常０～０．１倍モル、好ましくは０．００００５～０．０５倍モルである。 The amount of the oxidation catalyst used is not particularly limited, but is usually 0 to 0.1 times mol, preferably 0.00005 to 1 mol per 1 mol or 1 part by weight of 1- (substituted phenyl) -1-substituted alcohol compound. It is 0.05 times mole.
　本発明の反応に使用できる添加物としてはテトラ‐ｎ‐ブチルアンモニウムフルオリド、テトラ‐ｎ‐ブチルアンモニウムクロリド、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウム、硫酸水素　テトラ‐ｎ‐ブチルアンモニウム、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸水素カリウム、臭化ナトリウム、臭化カリウム、水酸化バリウム、水酸化カルシウム、炭酸バリウム、炭酸カルシウム、酢酸ナトリウム、酢酸カリウム、酢酸リチウム、燐酸カリウム、燐酸水素ジカリウム、燐酸二水素カリウム、ナトリウムメトキシド、カリウム‐ｔ‐ブトキシド、塩酸、トリメチルアミン、トリエチルアミン、トリ－ｎ－ブチルアミン、シンコニジン、トリメチルアミン‐Ｎ‐オキシド、トリ‐ｔ‐ブチルホスフィン、トリ‐ｎ‐ブチルホスフィン、又はフッ化セシウムが挙げられ、好ましくは、例えばテトラ‐ｎ‐ブチルアンモニウムクロリド、テトラ‐ｎ‐ブチルアンモニウムブロミド、硫酸水素　テトラ‐ｎ‐ブチルアンモニウム、炭酸カリウム、炭酸水素ナトリウム、臭化ナトリウム、臭化カリウム、炭酸ナトリウム、酢酸ナトリウム、酢酸カリウム、酢酸リチウム、燐酸カリウム、燐酸水素ジカリウム、燐酸二水素カリウム、塩酸、トリメチルアミン、トリエチルアミン、トリ－ｎ－ブチルアミン、テトラ‐ｎ‐ブチルアンモニウムフルオリド、酢酸　テトラ‐ｎ‐ブチルアンモニウム又はフッ化セシウムである。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。（１２）と（５）とからの（１３）の製造に用いる添加物としては、上記の添加物のうち、例えば、テトラ‐ｎ‐ブチルアンモニウムフルオリドまたはフッ化セシウムが特に好ましい。 Additives that can be used in the reaction of the present invention include tetra-n-butylammonium fluoride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, acetic acid tetra-n-butylammonium, hydrogen sulfate tetra-n- Butyl ammonium, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium bromide, potassium bromide, barium hydroxide, calcium hydroxide, barium carbonate, calcium carbonate, sodium acetate, Potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium methoxide, potassium tert-butoxide, hydrochloric acid, trimethylamine, triethylamine, tri-n-butylamine, cinchonidine, Examples include methylamine-N-oxide, tri-t-butylphosphine, tri-n-butylphosphine, or cesium fluoride. Preferably, for example, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, sulfuric acid Hydrogen tetra-n-butylammonium, potassium carbonate, sodium bicarbonate, sodium bromide, potassium bromide, sodium carbonate, sodium acetate, potassium acetate, lithium acetate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, hydrochloric acid, trimethylamine , Triethylamine, tri-n-butylamine, tetra-n-butylammonium fluoride, tetra-n-butylammonium acetate or cesium fluoride. These may be used singly or in combination of two or more. As the additive used for the production of (13) from (12) and (5), for example, tetra-n-butylammonium fluoride or cesium fluoride is particularly preferable among the above-mentioned additives.
　（１３）からの（２）の製造に用いる添加物としては、例えば、塩酸、トリメチルアミン、トリエチルアミン又はトリ－ｎ－ブチルアミンが好ましい。
　斯かる添加物の使用量は特に限定されないが、炭酸カリウム、炭酸水素ナトリウム、臭化ナトリウム及び臭化カリウム以外の添加物については、１－（置換フェニル）－１－置換アルコール化合物１モルまたは１重量部に対して、あるいは芳香族エステル化合物１モルに対して、通常０．００００１～０．１倍モル、好ましくは０．００００５～０．０５倍モルであり、臭化ナトリウム及び臭化カリウムについては、１－（置換フェニル）－１－置換アルコール化合物１モルに対して、通常０．０１～０．５倍モル、好ましくは０．０５～０．３倍モルであり、炭酸カリウム及び炭酸水素ナトリウムは、固体状態で使用しても良いが、１～１５重量％の水溶液として０．５～５重量部であるのが好ましい。 As the additive used for the production of (2) from (13), for example, hydrochloric acid, trimethylamine, triethylamine or tri-n-butylamine is preferable.
The amount of such additives used is not particularly limited, but for additives other than potassium carbonate, sodium hydrogen carbonate, sodium bromide and potassium bromide, 1 mol or 1- (substituted phenyl) -1-substituted alcohol compound is used. The amount is usually 0.00001 to 0.1 times mol, preferably 0.00005 to 0.05 times mol based on parts by weight or 1 mol of the aromatic ester compound. About sodium bromide and potassium bromide Is usually 0.01 to 0.5 times mol, preferably 0.05 to 0.3 times mol, per mol of 1- (substituted phenyl) -1-substituted alcohol compound, and potassium carbonate and hydrogen carbonate Sodium may be used in a solid state, but is preferably 0.5 to 5 parts by weight as a 1 to 15% by weight aqueous solution.
　本発明の反応に使用できる酸化剤としては、例えば、過塩素酸又はその塩、塩素酸又はその塩、亜塩素酸又はその塩、次亜塩素酸又はその塩、臭素酸又はその塩、亜臭素酸又はその塩、次亜臭素酸又はその塩、過よう素酸又はその塩が挙げられ、塩としては、例えば、アルカリ金属（リチウム、ナトリウムおよびカリウム）又はアルカリ土類金属（カルシウムおよびマグネシウム）が挙げられ、好ましくは過塩素酸ナトリウム、次亜塩素酸ナトリウム、次亜塩素酸カリウム、次亜塩素酸カルシウム、臭素酸ナトリウム、亜臭素酸ナトリウム、次亜臭素酸ナトリウム又は次亜臭素酸カリウムが挙げられ、特に好ましくは次亜塩素酸ナトリウム、次亜塩素酸カリウム、次亜塩素酸カルシウム又は次亜臭素酸ナトリウムである。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。
　斯かる酸化剤の使用量は特に限定されないが、１－（置換フェニル）－１－置換アルコール化合物１モルに対して、通常１～２倍モル、好ましくは１～１．５倍モルである。
　斯かる酸化剤は、所定の量を含有する水溶液の形で使用するのが好ましい。 Examples of the oxidizing agent that can be used in the reaction of the present invention include perchloric acid or its salt, chloric acid or its salt, chlorous acid or its salt, hypochlorous acid or its salt, bromic acid or its salt, bromine Examples include acids or salts thereof, hypobromite or salts thereof, periodic acid or salts thereof, and examples of the salts include alkali metals (lithium, sodium and potassium) or alkaline earth metals (calcium and magnesium). Preferably, sodium perchlorate, sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, sodium bromate, sodium bromite, sodium hypobromite or potassium hypobromite Particularly preferred are sodium hypochlorite, potassium hypochlorite, calcium hypochlorite or sodium hypobromite. These may be used singly or in combination of two or more.
The amount of such an oxidizing agent to be used is not particularly limited, but is usually 1 to 2 times mol, preferably 1 to 1.5 times mol, per mol of 1- (substituted phenyl) -1-substituted alcohol compound.
Such an oxidizing agent is preferably used in the form of an aqueous solution containing a predetermined amount.
　本発明の反応に使用できる水に可溶な有機溶媒としては、例えば、ジメチルスルホキシド、スルホラン、Ｎ，Ｎ‐ジメチルホルムアミド、Ｎ，Ｎ‐ジメチルアセトアミド、Ｎ‐メチル‐２‐ピロリドン、Ｎ，Ｎ’‐ジメチルエチレン尿素、ヘキサメチルリン酸トリアミド、アセトニトリル、プロピオニトリル、メタノール又はエタノール等が挙げられ、好ましくはジメチルスルホキシド、Ｎ，Ｎ‐ジメチルホルムアミド又はメタノールである。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。
　斯かる水に可溶な有機溶媒の使用量としては、芳香族アルデヒド化合物１重量部に対して、通常０．０１～１０重量部、好ましくは０．０１～５重量部、特に好ましくは０．１～４重量部である。 Examples of water-soluble organic solvents that can be used in the reaction of the present invention include dimethyl sulfoxide, sulfolane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, and N, N ′. -Dimethylethyleneurea, hexamethylphosphoric triamide, acetonitrile, propionitrile, methanol, ethanol or the like can be mentioned, and dimethyl sulfoxide, N, N-dimethylformamide or methanol is preferable. These may be used singly or in combination of two or more.
The amount of such an organic solvent soluble in water is usually 0.01 to 10 parts by weight, preferably 0.01 to 5 parts by weight, particularly preferably 0. 0 parts by weight based on 1 part by weight of the aromatic aldehyde compound. 1 to 4 parts by weight.
　本発明の反応に使用できる水に不溶な有機溶媒としては、例えば、ベンゼン、トルエン、キシレン、クロロベンゼン、ｏ‐ジクロロベンゼン又はメシチレン等のハロゲン原子で置換されてもよい芳香族炭化水素類、若しくはｎ‐ペンタン、ｎ‐ヘキサン、ｎ‐ヘプタン、ｎ‐オクタン、シクロペンタン、シクロヘキサン、メチルシクロヘキサン、塩化メチレン又は１，２‐ジクロロエタン等のハロゲン原子で置換されてもよい脂肪族炭化水素類が挙げられ、好ましくはトルエン、クロロベンゼン、ｎ‐ヘキサン、ｎ‐ヘプタン、シクロヘキサン、塩化メチレン又は１，２‐ジクロロエタンである。これらは単独で使用しても良いし、２種以上を混合して使用しても良い。 Examples of water-insoluble organic solvents that can be used in the reaction of the present invention include aromatic hydrocarbons that may be substituted with a halogen atom such as benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, or mesitylene, or n. Aliphatic hydrocarbons which may be substituted with halogen atoms such as -pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylcyclohexane, methylene chloride or 1,2-dichloroethane, Preferred is toluene, chlorobenzene, n-hexane, n-heptane, cyclohexane, methylene chloride or 1,2-dichloroethane. These may be used singly or in combination of two or more.
　本発明の反応に使用できる酸としては、フッ化水素酸、塩酸、臭化水素酸、よう化水素酸等のハロゲン化水素酸、硝酸、硫酸、燐酸、塩素酸、過塩素酸等の無機酸、メタンスルホン酸、エタンスルホン酸、トリフルオロメタンスルホン酸、ベンゼンスルホン酸、ｐ－トルエンスルホン酸等のスルホン酸、蟻酸、酢酸等の有機酸等が挙げられる。 Examples of the acid that can be used in the reaction of the present invention include hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydroiodic acid, and inorganic acids such as nitric acid, sulfuric acid, phosphoric acid, chloric acid, and perchloric acid. And sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, and organic acids such as formic acid and acetic acid.
　本発明の反応に使用できるフッ素源としては、例えばテトラブチルアンモニウムフルオリド等が挙げられる。 Examples of the fluorine source that can be used in the reaction of the present invention include tetrabutylammonium fluoride.
　本発明に係る反応のスキームを以下に示す。
Figure JPOXMLDOC01-appb-C000049
Figure JPOXMLDOC01-appb-C000050
 A reaction scheme according to the present invention is shown below.
Figure JPOXMLDOC01-appb-C000049
Figure JPOXMLDOC01-appb-C000050
　本発明の実施に当たっての出発原料となる式（４）で表される芳香族アルデヒド化合物は市販されているか、公知の方法で製造することができる。
　本発明の実施に当たっての出発原料となる式（５）で表される置換ケイ素化合物は市販されているか、公知の方法で製造することができる。
　本発明の実施に当たっての出発原料となる式（１２）で表される芳香族エステル化合物は市販されているか、公知の方法で製造することができる。 The aromatic aldehyde compound represented by the formula (4), which is a starting material for carrying out the present invention, is commercially available or can be produced by a known method.
The substituted silicon compound represented by the formula (5), which is a starting material for carrying out the present invention, is commercially available or can be produced by a known method.
The aromatic ester compound represented by the formula (12), which is a starting material for carrying out the present invention, is commercially available or can be produced by a known method.
　本発明に係る反応を実施するには、例えば、反応器に式（１）で表される１－（置換フェニル）－１－置換アルコール化合物と、トルエンに代表される溶媒、２，２，６，６‐テトラメチルピペリジン‐１‐オキシルや２－アザアダマンタン－Ｎ－オキシルに代表される酸化触媒、炭酸水素ナトリウム又はその水溶液や臭化カリウムに代表される添加物、次亜塩素酸ナトリウムに代表される酸化剤を仕込み、撹拌下、通常－２０～１２０℃、好ましくは－１０～６０℃、特に好ましくは－５～１０℃で、通常１分～２４時間、好ましくは１０分～１０時間程度反応させれば良い。 For carrying out the reaction according to the present invention, for example, a 1- (substituted phenyl) -1-substituted alcohol compound represented by the formula (1) and a solvent represented by toluene, 2, 2, 6 , 6-Tetramethylpiperidine-1-oxyl and 2-azaadamantane-N-oxyl oxidation catalysts, sodium bicarbonate or its aqueous solution and additives such as potassium bromide, sodium hypochlorite The oxidant is added, and is usually −20 to 120 ° C., preferably −10 to 60 ° C., particularly preferably −5 to 10 ° C., usually 1 minute to 24 hours, preferably about 10 minutes to 10 hours with stirring. What is necessary is just to make it react.
　例えば、反応器に式（３）で表される置換シリルエーテル化合物と、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシド、メタノールに代表される溶媒、塩酸に代表される酸および／またはフッ素源とを仕込み、蒸留水を添加してまたは添加しないで撹拌下、通常０～１２０℃、好ましくは１０～８０℃で、通常１０分～９６時間、好ましくは３０分～７２時間程度反応させれば良い。 For example, in a reactor, a substituted silyl ether compound represented by the formula (3), toluene, N, N-dimethylformamide, dimethyl sulfoxide, a solvent typified by methanol, an acid typified by hydrochloric acid and / or a fluorine source And with or without added distilled water, the reaction is usually carried out at 0 to 120 ° C., preferably 10 to 80 ° C., usually 10 minutes to 96 hours, preferably 30 minutes to 72 hours. .
　例えば、反応器に式（４）で表される芳香族アルデヒド化合物と式（５）で表される置換ケイ素化合物、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシドに代表される溶媒、炭酸カリウム、酢酸ナトリウム、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウムに代表される触媒とを仕込み、撹拌下、通常－２０～１２０℃、好ましくは－１０～６０℃で、通常１分～９６時間、好ましくは１５分～７２時間程度反応させれば良い。 For example, an aromatic aldehyde compound represented by the formula (4) and a substituted silicon compound represented by the formula (5), toluene, N, N-dimethylformamide, a solvent typified by dimethyl sulfoxide, potassium carbonate, Sodium acetate, tetra-n-butylammonium bromide, acetic acid and a catalyst typified by tetra-n-butylammonium acetic acid are added with stirring, usually at −20 to 120 ° C., preferably at −10 to 60 ° C., usually 1 minute to The reaction may be performed for 96 hours, preferably about 15 minutes to 72 hours.
　例えば、反応器に式（４）で表される芳香族アルデヒド化合物と式（５）で表される置換ケイ素化合物、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシドに代表される溶媒、炭酸カリウム、酢酸ナトリウム、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウムに代表される触媒とを仕込み、撹拌下、通常－２０～１２０℃、好ましくは－１０～６０℃で、通常１分～９６時間、好ましくは１５分～７２時間程度反応させ、得られた反応溶液にメタノールに代表される溶媒を追加又は追加せずに、塩酸に代表される添加物を追加し、撹拌下、通常０～１２０℃、好ましくは１０～８０℃で、通常１０分～９６時間、好ましくは３０分～７２時間程度反応させれば良い。 For example, an aromatic aldehyde compound represented by the formula (4) and a substituted silicon compound represented by the formula (5), toluene, N, N-dimethylformamide, a solvent typified by dimethyl sulfoxide, potassium carbonate, Sodium acetate, tetra-n-butylammonium bromide, acetic acid and a catalyst typified by tetra-n-butylammonium acetic acid are added with stirring, usually at −20 to 120 ° C., preferably at −10 to 60 ° C., usually 1 minute to The reaction is allowed to proceed for 96 hours, preferably 15 minutes to 72 hours, and an additive typified by hydrochloric acid is added to the resulting reaction solution with or without the addition of a solvent typified by methanol. The reaction may be carried out at ˜120 ° C., preferably 10˜80 ° C., usually for 10 minutes to 96 hours, preferably for 30 minutes to 72 hours.
　例えば、反応器に式（４）で表される芳香族アルデヒド化合物と式（５）で表される置換ケイ素化合物、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシドに代表される溶媒、炭酸カリウム、酢酸ナトリウム、テトラ‐ｎ‐ブチルアンモニウムブロミド、酢酸　テトラ‐ｎ‐ブチルアンモニウムに代表される触媒とを仕込み、撹拌下、通常－２０～１２０℃、好ましくは－１０～６０℃で、通常１分～９６時間、好ましくは１５分～７２時間程度反応させ、得られた反応溶液に水を添加してまたは添加せずに、他の有機溶媒、好ましくはメタノールに代表される前記の水に可溶な有機溶媒を添加してまたは添加せずに、塩酸に代表される酸および／またはフッ素源を追加し、撹拌下、通常０～１２０℃、好ましくは１０～８０℃で、通常１０分～９６時間、好ましくは３０分～７２時間程度反応させ、反応溶液に対して抽出操作を行い式（１）で表される化合物を含有する溶液を得て、さらに２，２，６，６‐テトラメチルピペリジン‐１‐オキシルや２－アザアダマンタン－Ｎ－オキシルに代表される酸化触媒、炭酸水素ナトリウム又はその水溶液や臭化カリウムに代表される添加物、次亜塩素酸ナトリウムに代表される酸化剤を仕込み、撹拌下、通常－２０～１２０℃、好ましくは－１０～６０℃、特に好ましくは－５～１０℃で、通常１分～２４時間、好ましくは１０分～１０時間程度反応させれば良い。 For example, an aromatic aldehyde compound represented by the formula (4) and a substituted silicon compound represented by the formula (5), toluene, N, N-dimethylformamide, a solvent typified by dimethyl sulfoxide, potassium carbonate, Sodium acetate, tetra-n-butylammonium bromide, acetic acid and a catalyst typified by tetra-n-butylammonium acetic acid are added with stirring, usually at −20 to 120 ° C., preferably at −10 to 60 ° C., usually 1 minute to The reaction is allowed to proceed for 96 hours, preferably about 15 minutes to 72 hours, and with or without the addition of water to the resulting reaction solution, it is soluble in the above-mentioned water typified by other organic solvents, preferably methanol. With or without the addition of an organic solvent, an acid typified by hydrochloric acid and / or a fluorine source is added, and with stirring, usually 0 to 120 ° C., preferably 10 to 8 The reaction is usually performed at 10 ° C. for about 10 minutes to 96 hours, preferably about 30 minutes to 72 hours, and the reaction solution is subjected to extraction operation to obtain a solution containing the compound represented by formula (1). Oxidation catalysts such as 2,6,6-tetramethylpiperidine-1-oxyl and 2-azaadamantane-N-oxyl, additives such as sodium bicarbonate or its aqueous solution and potassium bromide, hypochlorous acid An oxidizing agent typified by sodium is charged, and under stirring, usually at −20 to 120 ° C., preferably −10 to 60 ° C., particularly preferably −5 to 10 ° C., usually 1 minute to 24 hours, preferably 10 minutes to What is necessary is just to make it react for about 10 hours.
　例えば、反応器に式（１２）で表される安息香酸エステル化合物と、トルエンに代表される溶媒、式（５）で表される置換ケイ素化合物を仕込み、撹拌下、通常－５０～１２０℃、好ましくは－３０～６０℃、特に好ましくは－２０～１０℃で、触媒を溶液又は固体の状態で添加し、反応させれば良い。 For example, a benzoic acid ester compound represented by the formula (12) and a solvent typified by toluene and a substituted silicon compound represented by the formula (5) are charged in a reactor, and usually −50 to 120 ° C. with stirring. The catalyst may be added in the form of a solution or a solid, preferably at −30 to 60 ° C., particularly preferably at −20 to 10 ° C., and reacted.
　例えば、反応器に式（３）で表される置換シリルエーテル化合物と、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、ジメチルスルホキシド、メタノールに代表される溶媒、塩酸、トリエチルアミン、トリ－ｎ－ブチルアミンに代表される添加物とを仕込み、撹拌下、通常０～１２０℃、好ましくは１０～８０℃で、反応させれば良い。 For example, in a reactor, a substituted silyl ether compound represented by the formula (3), toluene, N, N-dimethylformamide, dimethyl sulfoxide, a solvent typified by methanol, hydrochloric acid, triethylamine, tri-n-butylamine Additives to be added and reacted under stirring at a temperature of usually 0 to 120 ° C., preferably 10 to 80 ° C.
　例えば、反応器に式（１２）で表される安息香酸エステル化合物と、トルエンに代表される溶媒、式（５）で表される置換ケイ素化合物を仕込み、撹拌下、通常－５０～１２０℃、好ましくは－３０～６０℃、特に好ましくは－２０～１０℃で、触媒を溶液又は固体の状態で添加し、反応させた後に、水を加え、アセトニトリルに代表される極性のある溶媒を加えてシリルエーテルを切断すれば良い。 For example, a benzoic acid ester compound represented by the formula (12) and a solvent typified by toluene and a substituted silicon compound represented by the formula (5) are charged in a reactor, and usually −50 to 120 ° C. with stirring. Preferably, the catalyst is added in a solution or solid state at −30 to 60 ° C., particularly preferably at −20 to 10 ° C., and after the reaction, water is added, and a polar solvent typified by acetonitrile is added. What is necessary is just to cut | disconnect silyl ether.
　次に、本発明の工程Ｃの出発物質として用いることのできる式（１）で表される１－（置換フェニル）－１－置換アルコール化合物の具体例及び工程Ｂの出発原料として用いることの出来る式（３）で表される置換シリルエーテル化合物の具体例を示すが、本発明はこれらのみに限定されるものではない。
　尚、Ｍｅとの記載はメチル基を表す。 Next, a specific example of a 1- (substituted phenyl) -1-substituted alcohol compound represented by formula (1) that can be used as a starting material in Step C of the present invention and a starting material in Step B can be used. Although the specific example of the substituted silyl ether compound represented by Formula (3) is shown, this invention is not limited only to these.
In addition, the description of Me represents a methyl group.
Figure JPOXMLDOC01-appb-C000051
Figure JPOXMLDOC01-appb-C000051
Figure JPOXMLDOC01-appb-C000052
Figure JPOXMLDOC01-appb-C000052
Figure JPOXMLDOC01-appb-C000053
Figure JPOXMLDOC01-appb-C000053
Figure JPOXMLDOC01-appb-C000054
Figure JPOXMLDOC01-appb-C000054
Figure JPOXMLDOC01-appb-C000055
Figure JPOXMLDOC01-appb-C000055
Figure JPOXMLDOC01-appb-C000056
Figure JPOXMLDOC01-appb-C000056
Figure JPOXMLDOC01-appb-C000057
Figure JPOXMLDOC01-appb-C000057
Figure JPOXMLDOC01-appb-C000058
Figure JPOXMLDOC01-appb-C000058
Figure JPOXMLDOC01-appb-C000059
Figure JPOXMLDOC01-appb-C000059
Figure JPOXMLDOC01-appb-C000060
Figure JPOXMLDOC01-appb-C000060
Figure JPOXMLDOC01-appb-C000061
Figure JPOXMLDOC01-appb-C000061
Figure JPOXMLDOC01-appb-C000062
Figure JPOXMLDOC01-appb-C000062
Figure JPOXMLDOC01-appb-C000063
Figure JPOXMLDOC01-appb-C000063
Figure JPOXMLDOC01-appb-C000064
Figure JPOXMLDOC01-appb-C000064
Figure JPOXMLDOC01-appb-C000065
Figure JPOXMLDOC01-appb-C000065
Figure JPOXMLDOC01-appb-C000066
Figure JPOXMLDOC01-appb-C000066
　次に、本発明の新規な製造中間体である式（６）～（８）で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物の具体例及び式（９）～（１１）で表される置換トリメチルシリルエーテル化合物の具体例を示すが、本発明はこれらのみに限定されるものではない。
　尚、Ｍｅとの記載はメチル基を表す。 Next, specific examples of 1- (substituted phenyl) -2,2,2-trifluoroethanol compounds represented by formulas (6) to (8), which are novel production intermediates of the present invention, and formula (9) Specific examples of the substituted trimethylsilyl ether compound represented by (11) are shown below, but the present invention is not limited to these.
In addition, the description of Me represents a methyl group.
Figure JPOXMLDOC01-appb-C000067
Figure JPOXMLDOC01-appb-C000067
Figure JPOXMLDOC01-appb-T000068
Figure JPOXMLDOC01-appb-T000068
Figure JPOXMLDOC01-appb-T000069
Figure JPOXMLDOC01-appb-T000069
Figure JPOXMLDOC01-appb-C000070
Figure JPOXMLDOC01-appb-C000070
Figure JPOXMLDOC01-appb-T000071
Figure JPOXMLDOC01-appb-T000071
Figure JPOXMLDOC01-appb-T000072
Figure JPOXMLDOC01-appb-T000072
Figure JPOXMLDOC01-appb-C000073
Figure JPOXMLDOC01-appb-C000073
Figure JPOXMLDOC01-appb-T000074
Figure JPOXMLDOC01-appb-T000074
Figure JPOXMLDOC01-appb-T000075
Figure JPOXMLDOC01-appb-T000075
Figure JPOXMLDOC01-appb-T000076
Figure JPOXMLDOC01-appb-T000076
Figure JPOXMLDOC01-appb-T000077
Figure JPOXMLDOC01-appb-T000077
Figure JPOXMLDOC01-appb-T000078
Figure JPOXMLDOC01-appb-T000078
Figure JPOXMLDOC01-appb-T000079
Figure JPOXMLDOC01-appb-T000079
Figure JPOXMLDOC01-appb-T000080
Figure JPOXMLDOC01-appb-T000080
Figure JPOXMLDOC01-appb-T000082
Figure JPOXMLDOC01-appb-T000082
Figure JPOXMLDOC01-appb-T000083
Figure JPOXMLDOC01-appb-T000083
　以下に本発明の実施例を示すが、本発明はこれらのみによって限定されるものではない。 Examples of the present invention are shown below, but the present invention is not limited to these examples.
［合成例］
〔実施例１〕
　３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの合成
〔実施例１－１〕
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノール０．４９ｇ（２．０ｍｍｏｌ）、トルエン２．４５ｇ、２，２，６，６－テトラメチルピペリジン－１－オキシル３．５ｍｇ（０．０２２ｍｍｏｌ）、臭化カリウム２６ｍｇ（０．２２ｍｍｏｌ）、蒸留水０．２５ｇを仕込み、０℃に冷却した。さらに、次亜塩素酸ナトリウム水溶液１．５ｍｌ（純正化学製、約２．２ｍｍｏｌ）を、反応液の温度が５℃を超えないように滴下した。さらに、０℃で２．５時間撹拌した。反応液に亜硫酸ナトリウム２５ｍｇ（０．２ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液を分液し、水層からトルエン４．９ｇを用いて抽出した。有機層を合わせ、飽和食塩水０．５ｍｌで洗浄し、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液７．６ｇを得た。この溶液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの面積百分率は９７．３％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。 [Synthesis example]
[Example 1]
Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone [Example 1-1]
1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol 0.49 g (2.0 mmol), toluene 2.45 g, 2,2,6,6-tetramethylpiperidine-1-oxyl 5 mg (0.022 mmol), potassium bromide 26 mg (0.22 mmol), and distilled water 0.25 g were charged and cooled to 0 ° C. Further, 1.5 ml of an aqueous sodium hypochlorite solution (manufactured by Junsei Chemical, about 2.2 mmol) was added dropwise so that the temperature of the reaction solution did not exceed 5 ° C. Furthermore, it stirred at 0 degreeC for 2.5 hours. To the reaction solution, 25 mg (0.2 mmol) of sodium sulfite was added and stirred at room temperature for 1 hour. The reaction solution was separated and extracted from the aqueous layer with 4.9 g of toluene. The organic layers were combined and washed with 0.5 ml of saturated brine to obtain 7.6 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. A small amount of this solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 97.3% ( Detection was carried out with a UV detector at a wavelength of 220 nm.
〔実施例１－２〕
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノール０．２５ｇ（１．０ｍｍｏｌ）、トルエン０．７４ｇ、２－アザアダマンタン－Ｎ－オキシル１０μｌ（０．０１ｍｍｏｌ　／　ｍｌのトルエン溶液、０．０００１ｍｍｏｌ）、５％炭酸水素ナトリウム水溶液０．７４ｇを仕込み、０℃に冷却した。さらに、次亜塩素酸ナトリウム水溶液０．８ｍｌ（約１．１ｍｍｏｌ）を添加し、０℃で３時間撹拌した。反応液に亜硫酸ナトリウム２５ｍｇ（０．２ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液を分液し、水層からトルエン２．５ｇを用いて抽出した。有機層を合わせ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液３．４ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの含有量は０．２４ｇであった（収率９８％）。 [Example 1-2]
0.25 g (1.0 mmol) of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol, 0.74 g of toluene, 10 μl of 2-azaadamantane-N-oxyl (0.01 mmol / ml of toluene) Solution, 0.0001 mmol), 0.74 g of 5% aqueous sodium hydrogen carbonate solution was charged, and cooled to 0 ° C. Further, 0.8 ml (about 1.1 mmol) of an aqueous sodium hypochlorite solution was added and stirred at 0 ° C. for 3 hours. To the reaction solution, 25 mg (0.2 mmol) of sodium sulfite was added and stirred at room temperature for 1 hour. The reaction solution was separated and extracted from the aqueous layer using 2.5 g of toluene. The organic layers were combined to obtain 3.4 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. When this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 0.24 g (yield 98%). ).
〔実施例１－３〕
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノール０．９８ｇ（４．０ｍｍｏｌ）、トルエン２．９４ｇ、２，２，６，６－テトラメチルピペリジン－１－オキシル５．９ｍｇ（０．０３８ｍｍｏｌ）、５％炭酸水素ナトリウム水溶液１．４７ｇを仕込み、０℃に冷却した。さらに、次亜塩素酸ナトリウム水溶液３．６ｍｌ（約４．４ｍｍｏｌ）を添加し、０℃で２時間撹拌した。反応液に亜硫酸ナトリウム０．１０ｇ（０．８ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液を分液し、水層からトルエン５．９ｇを用いて抽出した。有機層を合わせ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液８．１ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの含有量は０．９５ｇであった（収率９８％）。 Example 1-3
1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol 0.98 g (4.0 mmol), toluene 2.94 g, 2,2,6,6-tetramethylpiperidine-1-oxyl 9 mg (0.038 mmol) and 1.47 g of 5% aqueous sodium hydrogen carbonate solution were charged and cooled to 0 ° C. Furthermore, 3.6 ml (about 4.4 mmol) of an aqueous sodium hypochlorite solution was added, and the mixture was stirred at 0 ° C. for 2 hours. To the reaction solution was added 0.10 g (0.8 mmol) of sodium sulfite, and the mixture was stirred at room temperature for 1 hour. The reaction solution was separated and extracted from the aqueous layer using 5.9 g of toluene. The organic layers were combined to obtain 8.1 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. When this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 0.95 g (yield 98%). ).
〔実施例１－４〕
　実施例１－３と同様の操作を行うことにより得られた、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノン５．１７ｇを含むトルエン溶液を減圧下濃縮し、さらに、減圧蒸留にて精製した。８４～８９℃（１４ｍｍＨｇ）の留分として、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノン４．６８ｇを得た。 [Example 1-4]
A toluene solution containing 5.17 g of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone obtained by carrying out the same operation as in Example 1-3 was concentrated under reduced pressure, Purified by distillation. As a fraction at 84 to 89 ° C. (14 mmHg), 4.68 g of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was obtained.
〔実施例２〕
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの合成
　（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシラン１．６７ｇ、トルエン３．８１ｇ、メタノール１．９０ｇ、蒸留水０．７６ｇ、濃塩酸０．７６ｇを仕込み、３０℃にて４時間撹拌した。反応液に蒸留水３．８ｇ、トルエン３．８ｇを加え、分液した。さらに、水層からトルエン７．６ｇを用いて抽出した。有機層を合わせ、減圧下濃縮し、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノール０．８１ｇを得た（収率７９％）。
1H-NMR (CDCl3, Me4Si, 400MHz) δ7.41 (t, J = 1.8Hz, 1H), 7.39 (bs, 2H), 4.96-5.06 (m, 1H), 2.66 (d, J = 4.4Hz, 1H).
融点：４８～４９℃ [Example 2]
Synthesis of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane 1.67 g, toluene 3 .81 g, 1.90 g of methanol, 0.76 g of distilled water, and 0.76 g of concentrated hydrochloric acid were added and stirred at 30 ° C. for 4 hours. Distilled water (3.8 g) and toluene (3.8 g) were added to the reaction solution to separate the layers. Further, the aqueous layer was extracted with 7.6 g of toluene. The organic layers were combined and concentrated under reduced pressure to obtain 0.81 g of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol (yield 79%).
1 H-NMR (CDCl 3 , Me 4 Si, 400 MHz) δ7.41 (t, J = 1.8 Hz, 1H), 7.39 (bs, 2H), 4.96-5.06 (m, 1H), 2.66 (d, J = 4.4Hz, 1H).
Melting point: 48-49 ° C
〔実施例３〕
　（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの合成
　３，５－ジクロロベンズアルデヒド３．５ｇ（２０ｍｍｏｌ）、トルエン１０．５ｇ、ジメチルスルホキシド１．７５ｇ、トリフルオロメチルトリメチルシラン３．４１ｇ（２４ｍｍｏｌ）、炭酸カリウム５５ｍｇ（０．４ｍｍｏｌ）を仕込み、室温にて７時間撹拌した。反応液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの面積百分率は９８．３％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエン及びジメチルスルホキシドのピークは除外して計算した。）。反応液に冷蒸留水３．５ｍｌを加え、室温にて１０分撹拌した。反応液を分液し、有機層を飽和食塩水で洗浄し、減圧下濃縮した。微かに黄色の液体として粗（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシラン７．６ｇを得た。これを減圧蒸留にて精製し、１１６～１１８℃（１３ｍｍＨｇ）の留分として、無色液体の（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシラン６．０ｇを得た（収率９５％）。
1H-NMR (CDCl3, Me4Si, 400MHz) δ7.37 (t, J = 1.8Hz, 1H), 7.32-7.36 (m, 2H),  4.85 (q, J = 6.4Hz, 1H), 0.15 (s, 9H).
13C-NMR (CDCl3, Me4Si, 400MHz) δ138.8, 136.1, 129.3, 126.0, 123.7 (q, 1J(C, F) = 282.7Hz), 72.2 (q, 2J(C, F) = 32.8Hz), -0.36. Example 3
Synthesis of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane 3.5 g (20 mmol) of 3,5-dichlorobenzaldehyde, 10.5 g of toluene, 1.75 g of dimethyl sulfoxide, tri 3.41 g (24 mmol) of fluoromethyltrimethylsilane and 55 mg (0.4 mmol) of potassium carbonate were charged and stirred at room temperature for 7 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 3% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks for toluene and dimethyl sulfoxide). To the reaction solution, 3.5 ml of cold distilled water was added and stirred at room temperature for 10 minutes. The reaction mixture was separated, and the organic layer was washed with saturated brine and concentrated under reduced pressure. 7.6 g of crude (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was obtained as a slightly yellow liquid. This was purified by distillation under reduced pressure, and 6.0 g of colorless liquid (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was obtained as a fraction at 116 to 118 ° C. (13 mmHg). (Yield 95%).
1 H-NMR (CDCl 3 , Me 4 Si, 400MHz) δ7.37 (t, J = 1.8Hz, 1H), 7.32-7.36 (m, 2H), 4.85 (q, J = 6.4Hz, 1H), 0.15 (s, 9H).
13 C-NMR (CDCl 3 , Me 4 Si, 400 MHz) δ138.8, 136.1, 129.3, 126.0, 123.7 (q, 1 J (C, F) = 282.7Hz), 72.2 (q, 2 J (C, F ) = 32.8Hz), -0.36.
〔実施例４〕
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの１工程での合成
〔実施例４－１〕
　３，５－ジクロロベンズアルデヒド１．７５ｇ（１０ｍｍｏｌ）、トルエン７．０ｇ、Ｎ，Ｎ－ジメチルホルムアミド１．７５ｇ、トリフルオロメチルトリメチルシラン１．７１ｇ（１２ｍｍｏｌ）、炭酸カリウム４２ｍｇ（０．３０ｍｍｏｌ）を仕込み、室温にて２０時間撹拌した。反応液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの面積百分率は９８．２％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエン及びＮ，Ｎ‐ジメチルホルムアミドのピークは除外して計算した。）。反応液に蒸留水１ｍｌ、濃塩酸１ｍｌを加え、６０℃にて２時間、ついで、室温にて一晩撹拌した。反応液を分液し、水層からトルエン７ｇを用いて抽出した。有機層を合わせ、減圧下濃縮した。残分をシリカゲルカラムクロマトグラフィー（溶離液：ｎ－ヘキサン：酢酸エチルの７：１混合液）にて精製し、白色固体として１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノール２．３８ｇを得た（収率９７％）。 Example 4
Synthesis of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol in one step [Example 4-1]
3.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 7.0 g of toluene, 1.75 g of N, N-dimethylformamide, 1.71 g (12 mmol) of trifluoromethyltrimethylsilane, and 42 mg (0.30 mmol) of potassium carbonate are charged. And stirred at room temperature for 20 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks of toluene and N, N-dimethylformamide). Distilled water (1 ml) and concentrated hydrochloric acid (1 ml) were added to the reaction solution, followed by stirring at 60 ° C. for 2 hours and then at room temperature overnight. The reaction solution was separated and extracted from the aqueous layer using 7 g of toluene. The organic layers were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 7-: 1 mixture of n-hexane: ethyl acetate) to give 1- (3,5-dichlorophenyl) -2,2,2-trifluoro as a white solid. 2.38 g of ethanol was obtained (yield 97%).
〔実施例４－２〕
　３，５－ジクロロベンズアルデヒド０．７０ｇ（４．０ｍｍｏｌ）、ジメチルスルホキシド１．４ｇ、炭酸カリウム１１ｍｇ（０．０８ｍｍｏｌ）を仕込み、３０℃に加温した。トリフルオロメチルトリメチルシラン０．６８ｇ（４．８ｍｍｏｌ）を反応液の温度が３５℃を超えないように滴下し、３０℃にて２時間撹拌した。反応液に蒸留水０．４ｍｌ、濃塩酸０．２ｍｌを加え、３０℃にて１時間撹拌した。反応液を蒸留水４ｍｌにて希釈し、トルエン１０ｍｌ加え分液した。さらに、水層からトルエン５ｍｌを用いて抽出した。有機層を合わせ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールを含有する溶液１４．２ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの含有量は０．９１ｇであった（収率９３％）。 [Example 4-2]
Charged 0.70 g (4.0 mmol) of 3,5-dichlorobenzaldehyde, 1.4 g of dimethyl sulfoxide, and 11 mg (0.08 mmol) of potassium carbonate, and heated to 30 ° C. 0.68 g (4.8 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 2 hours. Distilled water (0.4 ml) and concentrated hydrochloric acid (0.2 ml) were added to the reaction solution, and the mixture was stirred at 30 ° C. for 1 hour. The reaction solution was diluted with 4 ml of distilled water, and 10 ml of toluene was added for liquid separation. Further, the aqueous layer was extracted with 5 ml of toluene. The organic layers were combined to obtain 14.2 g of a solution containing 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol. When this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol was 0.91 g (yield) 93%).
〔実施例５〕
　　３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの１工程での合成
〔実施例５－１〕
　３，５－ジクロロベンズアルデヒド１．７５ｇ（１０ｍｍｏｌ）、トルエン５．３ｇ、トリフルオロメチルトリメチルシラン１．７１ｇ（１２ｍｍｏｌ）、テトラ‐ｎ‐ブチルアンモニウムブロミド０．１６ｇ（０．５ｍｍｏｌ）、酢酸ナトリウム４１ｍｇ（０．５ｍｍｏｌ）を仕込み、３０℃にて２時間撹拌した。反応液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの面積百分率は９８．２％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。反応液に蒸留水０．８８ｇ、濃塩酸０．８７ｇ、メタノール２．６ｇを加え、３０℃にて３時間撹拌した。反応液に蒸留水５．３ｇ、トルエン５．３ｇを加え分液し、水層からトルエン１０．５ｇを用いて抽出した。有機層を合わせ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールを含む溶液２５．７ｇを得た。この溶液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの面積百分率は９７．４％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの溶液２５．７ｇの溶媒の一部を減圧下留去し、全量を９．８ｇとした。さらに、５％炭酸水素ナトリウム水溶液３．６７ｇ、２，２，６，６‐テトラメチルピペリジン‐１‐オキシル１５．６ｍｇ（０．１０ｍｍｏｌ）を加え、０℃に冷却した。ついで、次亜塩素酸ナトリウム水溶液８．８ｍｌを、５℃を超えないように添加し、０℃で１．５時間撹拌した。反応液に亜硫酸ナトリウム０．１５ｇ（１．２ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液に濃塩酸０．２５ｍｌを加え、分液し、水層からトルエン７．５ｇを用いて抽出した。有機層を合わせ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液１７．１ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの含有量は２．２６ｇであった（収率９２．９％）。 Example 5
Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone in one step [Example 5-1]
3.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 5.3 g of toluene, 1.71 g (12 mmol) of trifluoromethyltrimethylsilane, 0.16 g (0.5 mmol) of tetra-n-butylammonium bromide, 41 mg of sodium acetate ( 0.5 mmol), and stirred at 30 ° C. for 2 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak). Distilled water 0.88 g, concentrated hydrochloric acid 0.87 g, and methanol 2.6 g were added to the reaction solution, and the mixture was stirred at 30 ° C. for 3 hours. To the reaction solution, 5.3 g of distilled water and 5.3 g of toluene were added for liquid separation, and the aqueous layer was extracted with 10.5 g of toluene. The organic layers were combined to obtain 25.7 g of a solution containing 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol. A small amount of this solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol was 97.4%. (Detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peak of toluene.)
A portion of 25.7 g of the 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol solution was distilled off under reduced pressure to give a total amount of 9.8 g. Further, 3.67 g of 5% aqueous sodium hydrogen carbonate solution and 15.6 mg (0.10 mmol) of 2,2,6,6-tetramethylpiperidine-1-oxyl were added and cooled to 0 ° C. Subsequently, 8.8 ml of sodium hypochlorite aqueous solution was added so that it might not exceed 5 degreeC, and it stirred at 0 degreeC for 1.5 hours. Sodium sulfite (0.15 g, 1.2 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. Concentrated hydrochloric acid (0.25 ml) was added to the reaction solution, the phases were separated, and the aqueous layer was extracted with 7.5 g of toluene. The organic layers were combined to obtain 17.1 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. When this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 2.26 g (yield: 92. 9%).
〔実施例５－２〕
　３，５－ジクロロベンズアルデヒド１．７５ｇ（１０ｍｍｏｌ）、トルエン５．３ｇ、ジメチルスルホキシド１．１ｇ、炭酸カリウム２８ｍｇ（０．２ｍｍｏｌ）を仕込み、３０℃に加温した。トリフルオロメチルトリメチルシラン１．７１ｇ（１２ｍｍｏｌ）を反応液の温度が３５℃を超えないように滴下し、３０℃にて３時間撹拌した。反応液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの面積百分率は９８．５％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエン及びジメチルスルホキシドのピークは除外して計算した。）。反応液に蒸留水０．８８ｇ、濃塩酸０．８８ｇ、、メタノール２．１ｇを加え、３０℃にて３時間、ついで、室温にて一晩撹拌した。反応液に蒸留水５．３ｇを加え分液し、水層からトルエン１０．５ｇを用いて抽出した。有機層を合わせ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールを含む溶液１８．９ｇを得た。この溶液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの面積百分率は９７．６％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエン及びジメチルスルホキシドのピークは除外して計算した。）。
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの溶液１８．９ｇの溶媒の一部を減圧下濃縮し、全量を８．７ｇとした。さらに、５％炭酸水素ナトリウム水溶液３．３ｇ、２，２，６，６‐テトラメチルピペリジン‐１‐オキシル１３．６ｍｇ（０．０８７ｍｍｏｌ）を加え、０℃に冷却した。ついで、次亜塩素酸ナトリウム水溶液１０．７ｍｌを、５℃を超えないように添加し、０℃で３時間撹拌した。反応液に亜硫酸ナトリウム０．１５ｇ（１．２ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液に濃塩酸０．２５ｍｌを加え、分液し、水層からトルエン１３ｇを用いて抽出した。有機層を合わせ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液２１．７ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの含有量は２．３５ｇであった（収率９６．７％）。 [Example 5-2]
1.75 g (10 mmol) of 3,5-dichlorobenzaldehyde, 5.3 g of toluene, 1.1 g of dimethyl sulfoxide, and 28 mg (0.2 mmol) of potassium carbonate were charged and heated to 30 ° C. 1.71 g (12 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 3 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 98. 5% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peaks for toluene and dimethyl sulfoxide). Distilled water (0.88 g), concentrated hydrochloric acid (0.88 g), and methanol (2.1 g) were added to the reaction solution, and the mixture was stirred at 30 ° C. for 3 hours and then at room temperature overnight. The reaction solution was separated by adding 5.3 g of distilled water, and extracted from the aqueous layer with 10.5 g of toluene. The organic layers were combined to obtain 18.9 g of a solution containing 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol. A small amount of this solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. The area percentage of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol was 97.6%. (Detected with a UV detector at a wavelength of 220 nm. Calculations were made excluding the peaks for toluene and dimethyl sulfoxide.)
A portion of the 18.9 g solvent of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol solution was concentrated under reduced pressure to a total volume of 8.7 g. Further, 3.3 g of 5% aqueous sodium hydrogen carbonate solution and 13.6 mg (0.087 mmol) of 2,2,6,6-tetramethylpiperidine-1-oxyl were added and cooled to 0 ° C. Subsequently, 10.7 ml of sodium hypochlorite aqueous solution was added so that it might not exceed 5 degreeC, and it stirred at 0 degreeC for 3 hours. Sodium sulfite (0.15 g, 1.2 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 0.25 ml of concentrated hydrochloric acid, and the mixture was separated, and extracted from the aqueous layer with 13 g of toluene. The organic layers were combined to obtain 21.7 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. When this solution was analyzed by quantitative analysis using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 2.35 g (yield 96. 7%).
〔実施例５－３〕
　３，５－ジクロロベンズアルデヒド２．１ｇ（１２ｍｍｏｌ）、トルエン６．７ｇ、酢酸　テトラ‐ｎ‐ブチルアンモニウム９０ｍｇ（０．３ｍｍｏｌ）を仕込み、３０℃に加温した。トリフルオロメチルトリメチルシラン１．９０ｇ（１３．４ｍｍｏｌ）を反応液の温度が３５℃を超えないように滴下し、３０℃にて１．５時間撹拌した。反応液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエトキシ）トリメチルシランの面積百分率は９７．２％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。反応液に蒸留水０．８８ｇ、濃塩酸０．８８ｇ、メタノール５．３ｇを加え、３０℃にて１時間、ついで、室温にて一晩撹拌した。反応液に蒸留水１０．５ｇ、トルエン１０．５ｇを加え分液し、水層からトルエン１０．５ｇを用いて抽出した。有機層を合わせ、トルエンを一部減圧下留去し、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールを含む溶液４．２ｇを得た。この溶液を少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの面積百分率は９７．４％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。
　１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロエタノールの液体４．２ｇにトルエンを追加し、全量を１０．９ｇとした。さらに、５％炭酸水素ナトリウム水溶液４．１ｇ、２，２，６，６－テトラメチルピペリジン－１－オキシル１７．１ｍｇ（０．０９８ｍｍｏｌ）を加え、０℃に冷却した。ついで、次亜塩素酸ナトリウム水溶液９．８ｍｌを、５℃を超えないように添加し、０℃で２時間撹拌した。反応液に亜硫酸ナトリウム０．１５ｇ（１．２ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液に濃塩酸０．３ｍｌを加え、分液し、水層からトルエン１６．４ｇを用いて抽出した。有機層を合わせ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンを含有する溶液２８．５ｇを得た。この溶液を、高速液体クロマトグラフィーによる定量分析法にて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの含有量は２．６６ｇであった（収率９１．１％）。 [Example 5-3]
2.1 g (12 mmol) of 3,5-dichlorobenzaldehyde, 6.7 g of toluene, and 90 mg (0.3 mmol) of tetra-n-butylammonium acetate were charged and heated to 30 ° C. 1.90 g (13.4 mmol) of trifluoromethyltrimethylsilane was added dropwise so that the temperature of the reaction solution did not exceed 35 ° C., and the mixture was stirred at 30 ° C. for 1.5 hours. A small amount of the reaction solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. The area percentage of (1- (3,5-dichlorophenyl) -2,2,2-trifluoroethoxy) trimethylsilane was 97. 2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak). Distilled water (0.88 g), concentrated hydrochloric acid (0.88 g) and methanol (5.3 g) were added to the reaction mixture, and the mixture was stirred at 30 ° C. for 1 hour and then at room temperature overnight. Distilled water (10.5 g) and toluene (10.5 g) were added to the reaction solution, and the mixture was separated. The aqueous layer was extracted with 10.5 g of toluene. The organic layers were combined, and toluene was partially distilled off under reduced pressure to obtain 4.2 g of a solution containing 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol. A small amount of this solution was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol was 97.4%. (Detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peak of toluene.)
Toluene was added to 4.2 g of 1- (3,5-dichlorophenyl) -2,2,2-trifluoroethanol liquid to make the total amount 10.9 g. Further, 4.1 g of 5% aqueous sodium hydrogen carbonate solution and 17.1 mg (0.098 mmol) of 2,2,6,6-tetramethylpiperidine-1-oxyl were added and cooled to 0 ° C. Subsequently, 9.8 ml of sodium hypochlorite aqueous solution was added so that it might not exceed 5 degreeC, and it stirred at 0 degreeC for 2 hours. Sodium sulfite (0.15 g, 1.2 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 0.3 ml of concentrated hydrochloric acid, and the mixture was separated, and extracted from the aqueous layer with 16.4 g of toluene. The organic layers were combined to obtain 28.5 g of a solution containing 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone. When this solution was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 2.66 g (yield: 91. 1%).
〔実施例６〕
　３，５－ジクロロ安息香酸メチルエステルからの３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの合成
〔実施例６－１〕
　３，５－ジクロロ安息香酸メチルエステル３．０７５ｇ（１５ｍｍｏｌ）、トルエン３０ｍＬ、トリフルオロメチルトリメチルシラン２．６７ｇ（１８．７５ｍｍｏｌ）を仕込み、－２０℃に冷却した。濃度が１Ｍのテトラ－ｎ－ブチルアンモニウムフルオリドのテトラヒドロフラン溶液を９０μＬ（０．６ｍｏｌ％）滴下し、温度を－２０℃に保ったままで３０分間撹拌した。反応液を少量採り、水とアセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロ－１－メトキシエトキシ）トリメチルシランの面積百分率は９８．２％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。反応液に蒸留水１．５ｍＬ、濃塩酸３ｍＬ、メタノール７ｍＬを加え、７０℃にて一晩撹拌した。反応液を分液し、水層からトルエン１０ｍＬを用いて抽出した。有機層を合わせ、溶媒を留去した。ヘキサン５０ｍＬを加え、メタノールをディーンシュタークを用いて共沸留去し、減圧蒸留して３．１５ｇ（７８～８２℃／２０ｍｍＨｇ）の留分を得た。これを少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの面積百分率は９９．９％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。）。
（収率８６．５％）。 Example 6
Synthesis of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone from 3,5-dichlorobenzoic acid methyl ester [Example 6-1]
3.075 g (15 mmol) of 3,5-dichlorobenzoic acid methyl ester, 30 mL of toluene and 2.67 g (18.75 mmol) of trifluoromethyltrimethylsilane were charged and cooled to −20 ° C. 90 μL (0.6 mol%) of a tetrahydrofuran solution of tetra-n-butylammonium fluoride having a concentration of 1M was dropped, and the mixture was stirred for 30 minutes while maintaining the temperature at −20 ° C. A small amount of the reaction solution was taken, diluted with water and acetonitrile, and analyzed by high performance liquid chromatography. As a result, (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane was obtained. The area percentage was 98.2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak). Distilled water (1.5 mL), concentrated hydrochloric acid (3 mL), and methanol (7 mL) were added to the reaction solution, and the mixture was stirred at 70 ° C. overnight. The reaction solution was separated and extracted from the aqueous layer with 10 mL of toluene. The organic layers were combined and the solvent was distilled off. Hexane 50mL was added, methanol was azeotropically distilled off using Dean Stark, and distilled under reduced pressure to obtain 3.15 g (78-82 ° C./20 mmHg) fraction. A small amount of this was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. The area percentage of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 99.9% (UV It was detected at a wavelength of 220 nm with a detector.)
(Yield 86.5%).
〔実施例６－２〕
　３，５－ジクロロ安息香酸メチルエステル４１．０１ｇ（２００ｍｍｏｌ）、トルエン２６６ｍＬ、ジメトキシエタン１１４ｍＬ、フッ化セシウム０．６１ｇ（４ｍｍｏｌ）を仕込み、－２０℃に冷却した。トリフルオロメチルトリメチルシラン３４．１３ｇ（２４０ｍｍｏｌ）を滴下し、温度を－２０℃に保ったままで３０分間撹拌した。反応液を少量採り、水とアセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロ－１－メトキシエトキシ）トリメチルシランの面積百分率は９１．２％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。反応液に蒸留水３１ｍＬを加え室温にし、分液した。有機層を濃縮し、トリエチルアミン１．４２ｇ（１４ｍｍｏｌ）、メタノール２５９ｍｌを加え、６０℃にて１時間攪拌した。反応液を濃縮した後、ヘプタン２４０ｍｌを加えメタノールを共沸留去した。残分を減圧蒸留して４４．９６ｇ（１０３～１０４℃／２０ｍｍＨｇ）の留分を得た。これを少量採り、アセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、３’，５’－ジクロロ－２，２，２－トリフルオロアセトフェノンの面積百分率は９９．４％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。）。
（収率９２．５％）。 Example 6-2
A mixture of 41.01 g (200 mmol) of 3,5-dichlorobenzoic acid methyl ester, 266 mL of toluene, 114 mL of dimethoxyethane, and 0.61 g (4 mmol) of cesium fluoride was cooled to −20 ° C. 34.13 g (240 mmol) of trifluoromethyltrimethylsilane was added dropwise, and the mixture was stirred for 30 minutes while maintaining the temperature at −20 ° C. A small amount of the reaction solution was taken, diluted with water and acetonitrile, and analyzed by high performance liquid chromatography. As a result, (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane was obtained. The area percentage was 91.2% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the peak of toluene). Distilled water (31 mL) was added to the reaction solution to room temperature, followed by liquid separation. The organic layer was concentrated, 1.42 g (14 mmol) of triethylamine and 259 ml of methanol were added, and the mixture was stirred at 60 ° C. for 1 hour. After concentrating the reaction solution, 240 ml of heptane was added and methanol was distilled off azeotropically. The residue was distilled under reduced pressure to obtain a fraction of 44.96 g (103 to 104 ° C./20 mmHg). A small amount thereof was taken, diluted with acetonitrile, and analyzed by high performance liquid chromatography. As a result, the area percentage of 3 ′, 5′-dichloro-2,2,2-trifluoroacetophenone was 99.4% (UV It was detected at a wavelength of 220 nm with a detector.)
(Yield 92.5%).
〔実施例７〕
　（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロ－１－メトキシエトキシ）トリメチルシランの合成
　３，５－ジクロロ安息香酸メチルエステル０．４１０１ｇ（２ｍｍｏｌ）、ヘプタン４．８ｍＬ、トリフルオロメチルトリメチルシラン０．３６９７ｇ（２．６ｍｍｏｌ）を仕込み、０℃に冷却した。濃度が１Ｍのテトラ－ｎ－ブチルアンモニウムフルオリドのテトラヒドロフラン溶液４０μＬをトルエン０．２ｍＬに溶解し、それを滴下し、温度を０℃に保ったままで３０分間撹拌した。反応液を少量採り、水とアセトニトリルで希釈し、高速液体クロマトグラフィーにて分析したところ、（１－（３，５－ジクロロフェニル）－２，２，２－トリフルオロ－１－メトキシエトキシ）トリメチルシランの面積百分率は８６．３％であった（ＵＶ検出器にて２２０ｎｍの波長で検出した。トルエンのピークは除外して計算した。）。 Example 7
Synthesis of (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane 3,5-dichlorobenzoic acid methyl ester 0.4101 g (2 mmol), heptane 4.8 mL, Trifluoromethyltrimethylsilane 0.3697 g (2.6 mmol) was charged and cooled to 0 ° C. A tetrahydrofuran solution of tetra-n-butylammonium fluoride having a concentration of 1 M in 40 μL was dissolved in 0.2 mL of toluene, which was added dropwise, and stirred for 30 minutes while maintaining the temperature at 0 ° C. A small amount of the reaction solution was taken, diluted with water and acetonitrile, and analyzed by high performance liquid chromatography. As a result, (1- (3,5-dichlorophenyl) -2,2,2-trifluoro-1-methoxyethoxy) trimethylsilane was obtained. The area percentage was 86.3% (detected with a UV detector at a wavelength of 220 nm. Calculation was performed excluding the toluene peak).
〔実施例８〕
　２，２，２－トリフルオロ－１－（３－（トリフルオロメチル）フェニル）エタノンの合成
　３－（トリフルオロメチル）安息香酸メチルエステル２５．０ｇ（１２２．４ｍｍｏｌ）、トルエン１４０ｇ、ジメトキシエタン６０ｇ、フッ化セシウム０．９３ｇ（６．１２ｍｍｏｌ）を仕込み、－２０℃に冷却した。トリフルオロメチルトリメチルシラン２０．９ｇ（１４７．０ｍｍｏｌ）を滴下し、温度を－２０℃に保ったままで２時間撹拌した。反応液に蒸留水２０ｍＬを加え室温にし、分液した。有機層を濃縮し、メタノール１２０ｇ、３５％塩酸５ｍＬを加え、６０℃にて１時間攪拌した。反応液を濃縮した後、ヘキサン１００ｍＬを加えメタノールを共沸した。常圧で蒸留し２７．１ｇの２，２，２－トリフルオロ－１－（３－（トリフルオロメチル）フェニル）エタノンを得た（収率９１．４％）。 Example 8
Synthesis of 2,2,2-trifluoro-1- (3- (trifluoromethyl) phenyl) ethanone 3- (trifluoromethyl) benzoic acid methyl ester 25.0 g (122.4 mmol), toluene 140 g, dimethoxyethane 60 g Then, 0.93 g (6.12 mmol) of cesium fluoride was charged and cooled to −20 ° C. 20.9 g (147.0 mmol) of trifluoromethyltrimethylsilane was added dropwise, and the mixture was stirred for 2 hours while maintaining the temperature at −20 ° C. Distilled water (20 mL) was added to the reaction solution to room temperature, followed by liquid separation. The organic layer was concentrated, 120 g of methanol and 5 mL of 35% hydrochloric acid were added, and the mixture was stirred at 60 ° C. for 1 hour. After the reaction solution was concentrated, 100 mL of hexane was added to azeotrope methanol. Distillation at normal pressure gave 27.1 g of 2,2,2-trifluoro-1- (3- (trifluoromethyl) phenyl) ethanone (yield 91.4%).
　本発明の製造方法は、農薬、医薬及び各種化学品の中間体として有用な化合物である芳香族ケトン化合物、置換シリルエーテル化合物及び１－（置換フェニル）－１－置換アルコール化合物の製造方法として有用である。 The production method of the present invention is useful as a production method of aromatic ketone compounds, substituted silyl ether compounds and 1- (substituted phenyl) -1-substituted alcohol compounds, which are compounds useful as intermediates for agricultural chemicals, pharmaceuticals and various chemicals. It is.

Claims (20)

  1. 　式（１）：
    Figure JPOXMLDOC01-appb-C000001
     　［式中、Ｒ1は、Ｃ1～Ｃ6ハロアルキル又はＣ3～Ｃ8ハロシクロアルキルを表し、
    　Ｘは、ハロゲン原子、シアノ、ニトロ、－ＳＦ5、Ｃ1～Ｃ6アルキル、Ｃ3～Ｃ8シクロアルキル、Ｃ1～Ｃ6アルケニル、Ｃ1～Ｃ6アルキニル、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルケニル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、シアノ（Ｃ1～Ｃ6）アルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル、－ＯＨ、－ＯＲ5、ベンジルオキシ、－ＮＨ2、－Ｎ（Ｒ7）Ｒ6、－Ｓ（Ｏ）rＲ5又はフェニルスルホニルオキシを表し、ｍが２以上を表すとき、各々のＸは互いに同一であっても又は互いに相異なっていてもよく、
    　Ｒ5は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ4アルコキシ（Ｃ1～Ｃ4）アルキル、Ｃ1～Ｃ6ハロアルキル又はＣ1～Ｃ3ハロアルコキシ（Ｃ1～Ｃ3）ハロアルキルを表し、
    　Ｒ6は、Ｃ1～Ｃ6アルキル、－ＣＨＯ、Ｃ1～Ｃ6アルキルカルボニル、Ｃ1～Ｃ6ハロアルキルカルボニル、Ｃ1～Ｃ6アルコキシカルボニル、Ｃ1～Ｃ6アルキルチオカルボニル、Ｃ1～Ｃ6アルコキシチオカルボニル、Ｃ1～Ｃ6アルキルジチオカルボニル、Ｃ1～Ｃ6アルキルスルホニル又はＣ1～Ｃ6ハロアルキルスルホニルを表し、
    　Ｒ7は、水素原子又はＣ1～Ｃ6アルキルを表し、
    　ｍは、０～５の整数を表し、
    　ｒは、０～２の整数を表す。］　で表される１－（置換フェニル）－１－置換アルコール化合物を酸化触媒および添加物の存在下、酸化剤と反応させることによる式（２）：
    Figure JPOXMLDOC01-appb-C000002
     　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される芳香族ケトン化合物の製造方法。     Formula (1):
    Figure JPOXMLDOC01-appb-C000001
     [Wherein R 1 represents C 1 -C 6 haloalkyl or C 3 -C 8 halocycloalkyl,
    X is a halogen atom, cyano, nitro, —SF 5 , C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkenyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 , benzyloxy, —NH 2 , —N (R 7 ) R 6 , —S (O) r R 5 or Represents phenylsulfonyloxy, and when m represents 2 or more, each X may be the same as or different from each other;
    R 5 represents C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 6 haloalkyl or C 1 -C 3 haloalkoxy (C 1 -C 3 ) haloalkyl. ,
    R 6 is C 1 -C 6 alkyl, —CHO, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C Represents 6 alkoxythiocarbonyl, C 1 -C 6 alkyldithiocarbonyl, C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl,
    R 7 represents a hydrogen atom or C 1 -C 6 alkyl,
    m represents an integer of 0 to 5,
    r represents an integer of 0-2. A compound represented by formula (2) by reacting a 1- (substituted phenyl) -1-substituted alcohol compound represented by the following formula with an oxidizing agent in the presence of an oxidation catalyst and an additive:
    Figure JPOXMLDOC01-appb-C000002
     [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of the aromatic ketone compound represented by these.
  2. 　式（３）：
    Figure JPOXMLDOC01-appb-C000003
     　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表し、Ｒ2、Ｒ3およびＲ4は、Ｃ1～Ｃ6アルキル又は芳香族基を表す。］　で表される置換シリルエーテル化合物を水を添加してまたは添加しないで、他の有機溶媒を添加してまたは添加しないで、酸および／またはフッ素源と反応させることによる前記式（１）：
    Figure JPOXMLDOC01-appb-C000004
     　［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換アルコール化合物の製造方法。     Formula (3):
    Figure JPOXMLDOC01-appb-C000003
     [Wherein R 1 , X, and m represent the same meaning as described above, and R 2 , R 3, and R 4 represent C 1 -C 6 alkyl or an aromatic group. The above-described formula (1) is obtained by reacting the substituted silyl ether compound represented by the formula (1) with or without addition of water and with or without the addition of another organic solvent:
    Figure JPOXMLDOC01-appb-C000004
     [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of 1- (substituted phenyl) -1-substituted alcohol compound represented by these.
  3. 　式（４）：
    Figure JPOXMLDOC01-appb-C000005
     ［式中、Ｘ、ｍは前記と同様の意味を表す。］　で表される芳香族アルデヒド化合物と
    式（５）：
    Figure JPOXMLDOC01-appb-C000006
     　［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを溶媒中反応させることによる前記式（３）：
    Figure JPOXMLDOC01-appb-C000007
     ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｘ、ｍは前記と同様の意味を表す。］　で表される置換シリルエーテル化合物の製造方法。     Formula (4):
    Figure JPOXMLDOC01-appb-C000005
     [Wherein, X and m represent the same meaning as described above. ] An aromatic aldehyde compound represented by the formula (5):
    Figure JPOXMLDOC01-appb-C000006
     [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. The above formula (3) by reacting with a substituted silicon compound represented by the following formula:
    Figure JPOXMLDOC01-appb-C000007
     [Wherein, R 1 , R 2 , R 3 , R 4 , X, m represent the same meaning as described above. ] The manufacturing method of the substituted silyl ether compound represented by these.
  4. 　溶媒が水に不溶な有機溶媒であることを特徴とする請求項３記載の製造方法。 4. The production method according to claim 3, wherein the solvent is an organic solvent insoluble in water.
  5. 　溶媒が水に可溶な有機溶媒であることを特徴とする請求項３記載の製造方法。 4. The production method according to claim 3, wherein the solvent is an organic solvent soluble in water.
  6. 　溶媒が水に不溶な有機溶媒であり、水に可溶な有機溶媒を混合することを特徴とする請求項３記載の製造方法。 4. The method according to claim 3, wherein the solvent is an organic solvent insoluble in water, and an organic solvent soluble in water is mixed.
  7. 　前記式（４）：
    Figure JPOXMLDOC01-appb-C000008
     ［式中、Ｘ、ｍは前記と同様の意味を表す。］　で表される芳香族アルデヒド化合物と前記式（５）：
    Figure JPOXMLDOC01-appb-C000009
     ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを溶媒中反応させ、次いで、水を添加してまたは添加しないで、他の有機溶媒を添加してまたは添加しないで、酸および／またはフッ素源と反応させることにより前記式（１）：
    Figure JPOXMLDOC01-appb-C000010
     ［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換アルコール化合物を１工程で製造する方法。     Formula (4):
    Figure JPOXMLDOC01-appb-C000008
     [Wherein, X and m represent the same meaning as described above. ] An aromatic aldehyde compound represented by the formula (5):
    Figure JPOXMLDOC01-appb-C000009
     [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. And then reacting with the acid and / or fluorine source with or without the addition of water and with or without the addition of other organic solvents. According to the formula (1):
    Figure JPOXMLDOC01-appb-C000010
     [Wherein R 1 , X and m represent the same meaning as described above. A method for producing a 1- (substituted phenyl) -1-substituted alcohol compound represented by the following formula:
  8. 　前記式（４）で表される化合物と前記式（５）で表される化合物を反応させて得られる前記式（１）で表される化合物を含有する溶液を原料として用いる、請求項１記載の芳香族ケトン化合物の製造方法。 The solution containing the compound represented by the said Formula (1) obtained by making the compound represented by the said Formula (4) and the compound represented by the said Formula (5) react is used as a raw material. A process for producing an aromatic ketone compound.
  9. 　Ｘは、ハロゲン原子、シアノ、ニトロ、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6ハロアルキル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、シアノ（Ｃ1～Ｃ6）アルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル、－ＯＨ、－ＯＲ5、－ＮＨ2又は－Ｎ（Ｒ7）Ｒ6を表し、ｍが２以上を表すとき、各々のＸは互いに同一であっても又は互いに相異なっていてもよく、
    　Ｒ6は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6アルキルカルボニル、Ｃ1～Ｃ6ハロアルキルカルボニル又はＣ1～Ｃ6アルコキシカルボニルを表す請求項１～８のいずれかに記載の製造方法。     X is a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy (C 1 -C 6 ) haloalkyl, cyano (C 1 -C 6 ) alkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocycloalkyl, —OH, —OR 5 , —NH 2 or —N (R 7 ) represents R 6, when m is 2 or more, each X may be the or different from each other the same as each other,
    The production method according to any one of claims 1 to 8, wherein R 6 represents C 1 -C 6 alkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, or C 1 -C 6 alkoxycarbonyl.
  10. 　式（６）：
    Figure JPOXMLDOC01-appb-C000011
     ［式中、Ｙは、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、
    　Ｚは、塩素原子、臭素原子、よう素原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。     Formula (6):
    Figure JPOXMLDOC01-appb-C000011
     [Wherein Y represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio;
    Z represents a chlorine atom, bromine atom, iodine atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
  11. 式（７）：
    Figure JPOXMLDOC01-appb-C000012
     　［式中、Ｚは前記と同様の意味を表し、
    　Ｗは、臭素原子、よう素原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。     Formula (7):
    Figure JPOXMLDOC01-appb-C000012
     [Wherein Z represents the same meaning as described above,
    W represents a bromine atom, an iodine atom, a C 1 -C 6 haloalkyl, a C 1 -C 6 haloalkoxy or a C 1 -C 6 haloalkylthio. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
  12. 　式（８）：
    Figure JPOXMLDOC01-appb-C000013
     ［式中、Ｙ1は、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、Ｙ2は、ハロゲン原子、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ又はＣ1～Ｃ6ハロアルキルチオを表し、Ｚは前記と同様の意味を表す。］　で表される１－（置換フェニル）－２，２，２－トリフルオロエタノール化合物。     Formula (8):
    Figure JPOXMLDOC01-appb-C000013
     [Wherein Y 1 represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio, Y 2 represents a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 haloalkylthio is represented, and Z represents the same meaning as described above. ] The 1- (substituted phenyl) -2,2,2-trifluoroethanol compound represented by these.
  13. 　式（９）：
    Figure JPOXMLDOC01-appb-C000014
     ［式中、Ｙ、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。     Formula (9):
    Figure JPOXMLDOC01-appb-C000014
     [Wherein Y and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
  14. 　式（１０）：
    Figure JPOXMLDOC01-appb-C000015
     ［式中、Ｗ、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。     Formula (10):
    Figure JPOXMLDOC01-appb-C000015
     [Wherein W and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
  15. 　式（１１）：
    Figure JPOXMLDOC01-appb-C000016
     ［式中、Ｙ1、Ｙ2、Ｚは前記と同様の意味を表す。］　で表される置換トリメチルシリルエーテル化合物。     Formula (11):
    Figure JPOXMLDOC01-appb-C000016
     [Wherein Y 1 , Y 2 and Z represent the same meaning as described above. ] The substituted trimethylsilyl ether compound represented by these.
  16. 　式（１２）：
    Figure JPOXMLDOC01-appb-C000017
     ［式中、Ｒ8は、Ｃ1～Ｃ6アルキル、Ｃ1～Ｃ6アルケニル、Ｃ1～Ｃ6アルキニル、Ｃ3～Ｃ8シクロアルキル、Ｃ1～Ｃ6ハロアルキル、Ｃ1～Ｃ6ハロアルケニル、ヒドロキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6アルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ1～Ｃ6ハロアルコキシ（Ｃ1～Ｃ6）ハロアルキル、Ｃ3～Ｃ8ハロシクロアルキル又は芳香族基を表し、Ｘ、ｍは前記と同様の意味を表す。］　で表される安息香酸エステル化合物を式（５）：
    Figure JPOXMLDOC01-appb-C000018
     ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物と反応させることによる式（１３）：
    Figure JPOXMLDOC01-appb-C000019
     ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される置換シリルエーテル化合物の製造方法。     Formula (12):
    Figure JPOXMLDOC01-appb-C000017
     [Wherein R 8 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 halo. Alkenyl, hydroxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 alkoxy (C 1 -C 6 ) haloalkyl, C 1 -C 6 haloalkoxy (C 1 -C 6 ) haloalkyl, C 3 -C 8 halocyclo Represents an alkyl or aromatic group, and X and m represent the same meaning as described above. A benzoic acid ester compound represented by the formula (5):
    Figure JPOXMLDOC01-appb-C000018
     [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. ] Formula (13) by making it react with the substituted silicon compound represented by these:
    Figure JPOXMLDOC01-appb-C000019
     [Wherein, R 1 , R 2 , R 3 , R 4 , R 8 , X, m represent the same meaning as described above. ] The manufacturing method of the substituted silyl ether compound represented by these.
  17. 　式（１３）：
    Figure JPOXMLDOC01-appb-C000020
     　［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される置換シリルエーテル化合物を反応させることによる式（２）：
    Figure JPOXMLDOC01-appb-C000021
     ［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換カルボニル化合物の製造方法。     Formula (13):
    Figure JPOXMLDOC01-appb-C000020
     [Wherein, R 1 , R 2 , R 3 , R 4 , R 8 , X, m represent the same meaning as described above. ] Formula (2) by making the substituted silyl ether compound represented by these react:
    Figure JPOXMLDOC01-appb-C000021
     [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method of 1- (substituted phenyl) -1-substituted carbonyl compound represented by these.
  18. 　式（１２）：
    Figure JPOXMLDOC01-appb-C000022
     ［式中、Ｒ8、Ｘ、ｍは前記と同様の意味を表す。］　で表される安息香酸エステル化合物と式（５）：
    Figure JPOXMLDOC01-appb-C000023
     ［式中、Ｒ1、Ｒ2、Ｒ3、Ｒ4は前記と同様の意味を表す。］　で表される置換ケイ素化合物とを反応させることにより、式（２）：
    Figure JPOXMLDOC01-appb-C000024
     ［式中、Ｒ1、Ｘ、ｍは前記と同様の意味を表す。］　で表される１－（置換フェニル）－１－置換カルボニル化合物を１工程で製造する製造方法。     Formula (12):
    Figure JPOXMLDOC01-appb-C000022
     [Wherein R 8 , X and m represent the same meaning as described above. And a benzoic acid ester compound represented by the formula (5):
    Figure JPOXMLDOC01-appb-C000023
     [Wherein R 1 , R 2 , R 3 and R 4 represent the same meaning as described above. By reacting with a substituted silicon compound represented by the formula (2):
    Figure JPOXMLDOC01-appb-C000024
     [Wherein R 1 , X and m represent the same meaning as described above. ] The manufacturing method which manufactures the 1- (substituted phenyl) -1-substituted carbonyl compound represented by these by 1 process.
  19. 　ハロゲンで置換されていてもよい脂肪族炭化水素、ハロゲンで置換されていてもよい芳香族炭化水素またはその少なくとも一方を含む混合溶媒を溶媒として用いる請求項１６ないし１８のいずれかに記載の製造方法。 19. The production method according to claim 16, wherein a mixed solvent containing an aliphatic hydrocarbon optionally substituted with halogen, an aromatic hydrocarbon optionally substituted with halogen, or at least one of them is used as a solvent. .
  20. 　－５０℃より高い温度で反応を行う請求項１６ないし１９のいずれかに記載の製造方法。 The production method according to any one of claims 16 to 19, wherein the reaction is carried out at a temperature higher than -50 ° C.
PCT/JP2009/055309 2008-03-18 2009-03-18 Processes for production of 1-(substituted phenyl)-1- substituted silyl ethers, alcohols or ketones, and intermediates WO2009116577A1 (en)

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