Method for producing trifluoromethyl ketones and pentafluoroethyl ketones

Abstract

To provide production methods of trifluoromethyl ketones and pentafluoroethyl ketones, which are compounds useful as production intermediates of, e.g., electronic materials and medical and agricultural agents.SOLUTION: A production method is used in which an ester compound represented by the general formula (1) in the figure is reacted with trifluoromethane or pentafluoroethane in a glyme-based solvent in the presence of potassium hexamethyldisilazide to obtain a trifluoromethyl ketone or pentafluoroethyl ketone represented by the general formula (3) in the figure.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing trifluoromethyl ketones or pentafluoroethyl ketones by using trifluoromethane (also known as fluoroform, hereinafter referred to as "trifluoromethane") or pentafluoroethane as a raw material and subjecting ester compounds to a nucleophilic substitution reaction of a trifluoromethyl group or a pentafluoroethyl group. The obtained trifluoromethyl ketones and pentafluoroethyl ketones are useful compounds as intermediates for the production of pharmaceuticals, agricultural chemicals, electronic materials, etc. [Background technology]

[0002] Conventionally, a method of using trifluoromethyltrimethylsilane as a trifluoromethyl anion source and reacting it with an ester, and a method of using pentafluoroethyltrimethylsilane as a pentafluoroethyl anion source and reacting it with an ester are known (for example, see Non-Patent Documents 1 and 2). In addition, as a method for producing trifluoromethyl ketones from ester compounds using inexpensive trifluoromethane as a raw material, there is a method in which trifluoromethyl anions are generated using a metallic sodium dispersion in the presence of diisopropylamine (for example, see Non-Patent Document 3). On the other hand, as a method for trifluoromethylating ketones, a method is known in which inexpensive trifluoromethane is used as a source of trifluoromethyl anion as a raw material, and potassium tert-butoxide or potassium hexamethyldisilazide is used as a base in the presence of polyvalent ethers to generate trifluoromethyl anion and produce trifluoromethyl group-containing alcohols (see, for example, Patent Document 1).

[0003] In the conventional methods described in Non-Patent Documents 1 and 2, trifluoromethyltrimethylsilane or pentafluoroethyltrimethylsilane is used, which is relatively expensive, and therefore a cheaper source of perfluoroalkyl anions is desired. In addition, the method described in Non-Patent Document 3 has a problem that it is difficult to carry out on an industrial scale because it uses a water-repellent metallic sodium dispersion. Furthermore, the method described in Patent Document 1 is a method for producing trifluoromethyl group-containing alcohols by trifluoromethylating ketones, and differs from the method capable of producing trifluoromethyl ketones using esters as raw materials. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 6763747. [Non-patent literature]

[0005] [Non-Patent Document 1] Gongyong Li et al., Eur.J.Org.Chem.2019, 4658-4661. [Non-Patent Document 2] Massicot F. et al.,Org.Biomol.Chem.2011,9,600-603. [Non-Patent Document 3] George A. Olah et al., Angew. Chem. Int. Ed. 1998, 37, 820-821. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention provides a method for producing trifluoromethyl ketones or pentafluoroethyl ketones relatively cheaply and safely by reacting trifluoromethane or pentafluoroethane as a raw material with an ester. [Means for solving the problem]

[0007] The present inventors have conducted extensive research into a method for producing trifluoromethyl ketones or pentafluoroethyl ketones from ester compounds using trifluoromethane or pentafluoroethane as a raw material, and as a result have found that the target trifluoromethyl ketones or pentafluoroethyl ketones can be obtained in high yields by using relatively inexpensive potassium hexamethyldisilazide and a glyme-based solvent as a reaction solvent, thereby completing the present invention.

[0008] That is, the present invention relates to a compound represented by the following general formula (1): [ka] [In formula (1), R 1 is a naphthyl-1-yl group, a naphthyl-2-yl group, a 1-adamantyl group, a styryl group, or a group represented by the following general formula (2): [ka] (In formula (2), R 3 and R 4 each independently represents a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, a sec-butyl group, an isobutyl group, a tert-butyl group, a cyclohexyl group, a methoxy group, an ethoxy group, or a phenyl group, and R 2 indicates a methyl group or an ethyl group. The present invention relates to a method for producing an ester compound represented by the following general formula (3): [ka] [In formula (3), Rf represents a trifluoromethyl group or a pentafluoroethyl group, and R 1 is a naphthyl-1-yl group, a naphthyl-2-yl group, a 1-adamantyl group, a styryl group, or a group represented by the following general formula (2): [ka] (In formula (2), R 3 and R 4 each independently represents a hydrogen atom, a halogen atom, a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, a n-butyl group, a sec-butyl group, an iso-butyl group, a tert-butyl group, a cyclohexyl group, a methoxy group, an ethoxy group, or a phenyl group. The present invention provides a method for producing trifluoromethyl ketones or pentafluoroethyl ketones represented by the following formula: The glyme-based solvent is preferably triglyme and / or tetraglyme. Effect of the Invention

[0009] According to the present invention, there is provided an industrial production method which uses inexpensive trifluoromethane or pentafluoroethane and can give the target trifluoromethyl ketones or pentafluoroethyl ketones in higher yields than the ester compounds. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention will be described in detail below. The ester compounds represented by the general formula (1) applicable to the present invention are 2Specific examples of compounds in which R is a methyl group include methyl 1-naphthoate, methyl 2-naphthoate, methyl 1-adamantanecarboxylate, methyl (E)-3-phenylacrylate, methyl benzoate, methyl 2-fluorobenzoate, methyl 3-fluorobenzoate, methyl 4-fluorobenzoate, methyl 2-chlorobenzoate, methyl 3-chlorobenzoate, methyl 4-chlorobenzoate, methyl 2-bromobenzoate, methyl 3-bromobenzoate, methyl 4-bromobenzoate, methyl 2-iodobenzoate, methyl 3-iodobenzoate, methyl 4-iodobenzoate, Methyl 2-methylbenzoate, Methyl 3-methylbenzoate, Methyl 4-methylbenzoate, Methyl 2-ethylbenzoate, Methyl 3-ethylbenzoate, Methyl 4-ethylbenzoate, Methyl 2-n-propylbenzoate, Methyl 3-n-propylbenzoate, Methyl 4-n-propylbenzoate, Methyl 2-iso-propylbenzoate, Methyl 3-iso-propylbenzoate, Methyl 4-iso-propylbenzoate, Methyl 2-n-butylbenzoate, Methyl 3-n-butylbenzoate, Methyl 4-n-butylbenzoate, Methyl 2-iso-butylbenzoate, Methyl 3-iso -butylbenzoate, methyl 4-iso-butylbenzoate, methyl 2-sec-butylbenzoate, methyl 3-sec-butylbenzoate, methyl 4-sec-butylbenzoate, methyl 2-tert-butylbenzoate, methyl 3-tert-butylbenzoate, methyl 4-tert-butylbenzoate, methyl 2-cyclohexylbenzoate, methyl 3-cyclohexylbenzoate, methyl 4-cyclohexylbenzoate, methyl 2-methoxybenzoate, methyl 3-methoxybenzoate, methyl 4-methoxybenzoate, methyl 2-ethoxybenzoate, 3-ethoxy Methyl benzoate, methyl 4-ethoxybenzoate, methyl 2-phenylbenzoate, methyl 3-phenylbenzoate, methyl 4-phenylbenzoate, methyl 2,3-difluorobenzoate, methyl 2,4-difluorobenzoate, methyl 2,5-difluorobenzoate, methyl 2,6-difluorobenzoate, methyl 3,4-difluorobenzoate, methyl 3,5-difluorobenzoate, methyl 2,3-dichlorobenzoate, methyl 2,4-dichlorobenzoate, methyl 2,5-dichlorobenzoate, methyl 2,6-dichlorobenzoate, methyl 3,4-dichlorobenzoate, 3,Methyl 5-dichlorobenzoate, Methyl 2,3-dibromobenzoate, Methyl 2,4-dibromobenzoate, Methyl 2,5-dibromobenzoate, Methyl 2,6-dibromobenzoate, Methyl 3,4-dibromobenzoate, Methyl 3,5-dibromobenzoate, Methyl 2,3-diiodobenzoate, Methyl 2,4-diiodobenzoate, Methyl 2,5-diiodobenzoate, Methyl 2,6-diiodobenzoate, Methyl 3,4-diiodobenzoate, Methyl 3,5-diiodobenzoate, Methyl 2,3-dimethylbenzoate, Methyl 2,4-dimethylbenzoate, 2,5-dimethylbenzoate methyl benzoate, methyl 2,6-dimethylbenzoate, methyl 3,4-dimethylbenzoate, methyl 3,5-dimethylbenzoate, methyl 2,3-diethylbenzoate, methyl 2,4-diethylbenzoate, methyl 2,5-diethylbenzoate, methyl 2,6-diethylbenzoate, methyl 3,4-diethylbenzoate, methyl 3,5-diethylbenzoate, methyl 2,3-di-n-propylbenzoate, methyl 2,4-di-n-propylbenzoate, methyl 2,5-di-n-propylbenzoate, methyl 2,6-di-n-propylbenzoate, methyl 3,4-di-n-propylbenzoate, Methyl 3,5-di-n-propylbenzoate, methyl 2,3-di-iso-propylbenzoate, methyl 2,4-di-iso-propylbenzoate, methyl 2,5-di-iso-propylbenzoate, methyl 2,6-di-iso-propylbenzoate, methyl 3,4-di-iso-propylbenzoate, methyl 3,5-di-iso-propylbenzoate, methyl 2,3-di-n-butylbenzoate, methyl 2,4-di-n-butylbenzoate, methyl 2,5-di-n-butylbenzoate, methyl 2,6-di-n-butylbenzoate, methyl 3,4-di-n-butylbenzoate, 3, 5-di-n-butylbenzoic acid methyl ester, 2,3-di-iso-butylbenzoic acid methyl ester, 2,4-di-iso-butylbenzoic acid methyl ester, 2,5-di-iso-butylbenzoic acid methyl ester, 2,6-di-iso-butylbenzoic acid methyl ester, 3,4-di-iso-butylbenzoic acid methyl ester, 3,5-di-iso-butylbenzoic acid methyl ester, 2,3-di-sec-butylbenzoic acid methyl ester, 2,4-di-sec-butylbenzoic acid methyl ester, 2,5-di-sec-butylbenzoic acid methyl ester, 2,6-di-sec-butylbenzoic acid methyl ester, 3,4-di-sec-butylbenzoic acid methyl ester, 3,Methyl 5-di-sec-butylbenzoate, Methyl 2,3-di-tert-butylbenzoate, Methyl 2,4-di-tert-butylbenzoate, Methyl 2,5-di-tert-butylbenzoate, Methyl 2,6-di-tert-butylbenzoate, Methyl 3,4-di-tert-butylbenzoate, Methyl 3,5-di-tert-butylbenzoate, Methyl 2,3-dicyclohexylbenzoate, Methyl 2,4-dicyclohexylbenzoate, Methyl 2,5-dicyclohexylbenzoate, Methyl 2,6-dicyclohexylbenzoate, Methyl 3,4-dicyclohexylbenzoate Examples of the benzoic acid methyl ester include methyl cyclohexylbenzoate, methyl 3,5-dicyclohexylbenzoate, methyl 2,3-dimethoxybenzoate, methyl 2,4-dimethoxybenzoate, methyl 2,5-dimethoxybenzoate, methyl 2,6-dimethoxybenzoate, methyl 3,4-dimethoxybenzoate, methyl 3,5-dimethoxybenzoate, methyl 2,3-diethoxybenzoate, methyl 2,4-diethoxybenzoate, methyl 2,5-diethoxybenzoate, methyl 2,6-diethoxybenzoate, methyl 3,4-diethoxybenzoate, and methyl 3,5-diethoxybenzoate.

[0011] The ester compounds represented by the general formula (1) applicable to the present invention are 2Specific examples of compounds in which the substituent is an ethyl group include ethyl 1-naphthoate, ethyl 2-naphthoate, ethyl 1-adamantanecarboxylate, ethyl (E)-3-phenylacrylate, ethyl benzoate, ethyl 2-fluorobenzoate, ethyl 3-fluorobenzoate, ethyl 4-fluorobenzoate, ethyl 2-chlorobenzoate, ethyl 3-chlorobenzoate, ethyl 4-chlorobenzoate, ethyl 2-bromobenzoate, ethyl 3-bromobenzoate, ethyl 4-bromobenzoate, ethyl 2-iodobenzoate, ethyl 3-iodobenzoate, ethyl 4-iodobenzoate, Ethyl 2-methylbenzoate, Ethyl 3-methylbenzoate, Ethyl 4-methylbenzoate, Ethyl 2-ethylbenzoate, Ethyl 3-ethylbenzoate, Ethyl 4-ethylbenzoate, Ethyl 2-n-propylbenzoate, Ethyl 3-n-propylbenzoate, Ethyl 4-n-propylbenzoate, Ethyl 2-iso-propylbenzoate, Ethyl 3-iso-propylbenzoate, Ethyl 4-iso-propylbenzoate, Ethyl 2-n-butylbenzoate, Ethyl 3-n-butylbenzoate, Ethyl 4-n-butylbenzoate, Ethyl 2-iso-butylbenzoate, Ethyl 3-iso -butylbenzoate, ethyl 4-iso-butylbenzoate, ethyl 2-sec-butylbenzoate, ethyl 3-sec-butylbenzoate, ethyl 4-sec-butylbenzoate, ethyl 2-tert-butylbenzoate, ethyl 3-tert-butylbenzoate, ethyl 4-tert-butylbenzoate, ethyl 2-cyclohexylbenzoate, ethyl 3-cyclohexylbenzoate, ethyl 4-cyclohexylbenzoate, ethyl 2-methoxybenzoate, ethyl 3-methoxybenzoate, ethyl 4-methoxybenzoate, ethyl 2-ethoxybenzoate, 3-ethoxy Ethyl benzoate, Ethyl 4-ethoxybenzoate, Ethyl 2-phenylbenzoate, Ethyl 3-phenylbenzoate, Ethyl 4-phenylbenzoate, Ethyl 2,3-difluorobenzoate, Ethyl 2,4-difluorobenzoate, Ethyl 2,5-difluorobenzoate, Ethyl 2,6-difluorobenzoate, Ethyl 3,4-difluorobenzoate, Ethyl 3,5-difluorobenzoate, Ethyl 2,3-dichlorobenzoate, Ethyl 2,4-dichlorobenzoate, Ethyl 2,5-dichlorobenzoate, Ethyl 2,6-dichlorobenzoate, Ethyl 3,4-dichlorobenzoate, Ethyl 3,Ethyl 5-dichlorobenzoate, Ethyl 2,3-dibromobenzoate, Ethyl 2,4-dibromobenzoate, Ethyl 2,5-dibromobenzoate, Ethyl 2,6-dibromobenzoate, Ethyl 3,4-dibromobenzoate, Ethyl 3,5-dibromobenzoate, Ethyl 2,3-diiodobenzoate, Ethyl 2,4-diiodobenzoate, Ethyl 2,5-diiodobenzoate, Ethyl 2,6-diiodobenzoate, Ethyl 3,4-diiodobenzoate, Ethyl 3,5-diiodobenzoate, Ethyl 2,3-dimethylbenzoate, Ethyl 2,4-dimethylbenzoate, Ethyl 2,5-dimethylbenzoate ethyl benzoate, ethyl 2,6-dimethylbenzoate, ethyl 3,4-dimethylbenzoate, ethyl 3,5-dimethylbenzoate, ethyl 2,3-diethylbenzoate, ethyl 2,4-diethylbenzoate, ethyl 2,5-diethylbenzoate, ethyl 2,6-diethylbenzoate, ethyl 3,4-diethylbenzoate, ethyl 3,5-diethylbenzoate, ethyl 2,3-di-n-propylbenzoate, ethyl 2,4-di-n-propylbenzoate, ethyl 2,5-di-n-propylbenzoate, ethyl 2,6-di-n-propylbenzoate, ethyl 3,4-di-n-propylbenzoate, Ethyl 3,5-di-n-propylbenzoate, Ethyl 2,3-di-iso-propylbenzoate, Ethyl 2,4-di-iso-propylbenzoate, Ethyl 2,5-di-iso-propylbenzoate, Ethyl 2,6-di-iso-propylbenzoate, Ethyl 3,4-di-iso-propylbenzoate, Ethyl 3,5-di-iso-propylbenzoate, Ethyl 2,3-di-n-butylbenzoate, Ethyl 2,4-di-n-butylbenzoate, Ethyl 2,5-di-n-butylbenzoate, Ethyl 2,6-di-n-butylbenzoate, Ethyl 3,4-di-n-butylbenzoate, Ethyl 3, Ethyl 5-di-n-butylbenzoate, Ethyl 2,3-di-iso-butylbenzoate, Ethyl 2,4-di-iso-butylbenzoate, Ethyl 2,5-di-iso-butylbenzoate, Ethyl 2,6-di-iso-butylbenzoate, Ethyl 3,4-di-iso-butylbenzoate, Ethyl 3,5-di-iso-butylbenzoate, Ethyl 2,3-di-sec-butylbenzoate, Ethyl 2,4-di-sec-butylbenzoate, Ethyl 2,5-di-sec-butylbenzoate, Ethyl 2,6-di-sec-butylbenzoate, Ethyl 3,4-di-sec-butylbenzoate, Ethyl 3,Ethyl 5-di-sec-butylbenzoate, Ethyl 2,3-di-tert-butylbenzoate, Ethyl 2,4-di-tert-butylbenzoate, Ethyl 2,5-di-tert-butylbenzoate, Ethyl 2,6-di-tert-butylbenzoate, Ethyl 3,4-di-tert-butylbenzoate, Ethyl 3,5-di-tert-butylbenzoate, Ethyl 2,3-dicyclohexylbenzoate, Ethyl 2,4-dicyclohexylbenzoate, Ethyl 2,5-dicyclohexylbenzoate, Ethyl 2,6-dicyclohexylbenzoate, Ethyl 3,4-dicyclohexylbenzoate Examples of the benzoic acid ethyl ester include ethyl cyclohexylbenzoate, ethyl 3,5-dicyclohexylbenzoate, ethyl 2,3-dimethoxybenzoate, ethyl 2,4-dimethoxybenzoate, ethyl 2,5-dimethoxybenzoate, ethyl 2,6-dimethoxybenzoate, ethyl 3,4-dimethoxybenzoate, ethyl 3,5-dimethoxybenzoate, ethyl 2,3-diethoxybenzoate, ethyl 2,4-diethoxybenzoate, ethyl 2,5-diethoxybenzoate, ethyl 2,6-diethoxybenzoate, ethyl 3,4-diethoxybenzoate, and ethyl 3,5-diethoxybenzoate.

[0012] Specific examples of the ketones represented by the general formula (3) which can be produced by the present invention and in which Rf is a trifluoromethyl group include 2,2,2-trifluoro-1-(naphthalene-1-yl)ethan-1-one, 2,2,2-trifluoro-1-(naphthalene-2-yl)ethan-1-one, 1-[(3r,5r,7r)-adamantan-1-yl]-2,2,2-trifluoroethan-1-one, (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one, 2,2,2-trifluoro-1-phenylethan-1-one, 2,2,2-trifluoro-1-phenylethan-1-one, and 2,2,2-trifluoro-1-phenylethan-1-one. 2,2,2-trifluoro-1-(2-fluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-fluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-fluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-chlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-chlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-chlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-bromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-bromophenyl)ethan-1-one, Trifluoro-1-(3-bromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-bromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-iodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-iodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-iodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-methylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-methylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-methylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-methylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-methylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-ethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-ethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-ethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-n-propylphenyl)ethan-1-one, 2,2,2-Trifluoro-1-(2-isopropylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-isopropylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-isopropylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-is o-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-tert-butylphenyl)ethane -1-one, 2,2,2-trifluoro-1-(3-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-cyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-cyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-cyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-methoxy ... Fluoro-1-(3-methoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-ethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-ethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-ethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2-phenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3-phenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(4-phenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-difluorophenyl)ethan-1-one, 2,2,2-trifluoro-1- (2,3-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-dichlorophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-dibromophenyl)ethan-1-one , 2,2,2-trifluoro-1-(2,4-dibromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-dibromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-dibromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-dibromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-dibromophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4- diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-diiodophenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-dimethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-diethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-diethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-diethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-diethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-diethylphenyl)ethan-1-one,, 2,2,2-trifluoro-1-(3,5-diethylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-di-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-di-n-propylphenyl)ethan-1-one , 2,2,2-trifluoro-1-(3,5-di-n-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-iso-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-iso-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-iso-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-di-iso-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-di-iso-propylphenyl)ethan-1-one 2,2,2-trifluoro-1-(3,5-di-iso-propylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-di-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-di-n- butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-di-n-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-di-iso-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6 ... 2,2,2-trifluoro-1-(3,4-di-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-di-sec-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-di-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-di-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-di-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-di-tert-butylphenyl)ethan-1-one 2,2,2-trifluoro-1-(3,4-di-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-di-tert-butylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-dicyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-dicyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-dicyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-dicyclohexylphenyl)ethan-1-one 2,2,2-trifluoro-1-(3,4-dicyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-dicyclohexylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,5-dimethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-diethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-diethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-diethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-diethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-diethoxyphenyl)ethan-1-one, 2,2, Examples of the fluorophenyl ether include 2-trifluoro-1-(3,5-diethoxyphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,3-diphenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,4-diphenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,5-diphenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(2,6-diphenylphenyl)ethan-1-one, 2,2,2-trifluoro-1-(3,4-diphenylphenyl)ethan-1-one, and 2,2,2-trifluoro-1-(3,5-diphenylphenyl)ethan-1-one.

[0013] Specific examples of the ketones represented by the general formula (3) which can be produced by the present invention and in which Rf is a pentafluoroethyl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)propan-1-one, 1-[(3r,5r,7r)-adamantan-1-yl]-2,2,3,3,3-pentafluoropropan-1-one, (E)-1,1,1,2,2-pentafluoro-5-phenylpent-4-en-3-one, 2,2,3,3 ,3-pentafluoro-1-phenylpropan-1-one, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-fluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-chlorophenyl)propan-1-one, 2,2,3,3,3- Pentafluoro-1-(4-chlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-bromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-bromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-iodophenyl)propan-1-one, 2,2,3,3,3 -Pentafluoro-1-(4-iodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-methylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-methylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-ethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-ethylphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(4-ethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-isopropylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-isopropylphenyl) 2,2,3,3,3-pentafluoro-1-(4-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro 2,2,3,3,3-pentafluoro-1-(3-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-tert-butylphenyl )propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-cyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-cyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-cyclohexylphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(2-methoxyphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(3-methoxyphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(4-methoxyphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(2-ethoxyphenyl)propan-1-one, 2,2,3,3,3-Pentafluoro-1-(3-ethoxyphenyl)propan-1-one 2,2,3,3,3-pentafluoro-1-(4-ethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2-phenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3-phenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(4-phenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5 -difluorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-dichlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-dichlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-dichlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-dichlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-dichlorophenyl)propan-1-one, 2,2,3,3, 3-Pentafluoro-1-(3,5-dichlorophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-dibromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-dibromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-dibromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-dibromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-dibromophenyl)propan 2,2,3,3,3-pentafluoro-1-(3,5-dibromophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-diiodophenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-dimethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-dimethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-dimethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-dimethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-dimethylphenyl) Propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-dimethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-diethylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-di-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-di-n-propylphenyl)propan-1-one, 2,2,3,3,3- Pentafluoro-1-(3,4-di-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-di-n-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro 2,2,3,3,3-pentafluoro-1-(2,6-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-di-iso-propylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro Fluoro-1-(2,5-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-di-n-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-di-iso-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2, 3-di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5 -di-sec-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-( 3,4-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-di-tert-butylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-dicyclohexylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2, 5-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-dimethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-diethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,4-diethoxyphenyl) 2,2,3,3,3-pentafluoro-1-(2,5-diethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-diethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-diethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-diethoxyphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,3-diphenylphenyl)propan-1-one , 2,2,3,3,3-pentafluoro-1-(2,4-diphenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,5-diphenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(2,6-diphenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,4-diphenylphenyl)propan-1-one, 2,2,3,3,3-pentafluoro-1-(3,5-diphenylphenyl)propan-1-one, and the like.

[0014] The amount of potassium hexamethyldisilazide that can be used in the present invention is 1.0 to 5.0 moles per mole of the ester compound used in the reaction.

[0015] The amount of trifluoromethane applicable to the present invention is 1.0 molar or more per mole of the ester compounds used in the reaction, but since trifluoromethane is a gas and has low solubility in various solvents, it may be supplied to the reaction system in an excess of 5.0 molar amounts or more by bubbling. The excess trifluoromethane may be recovered and reused.

[0016] Examples of glyme-based solvents that can be used in the present invention include diglyme, ethyl diglyme, butyl diglyme, methyl ethyl diglyme, triglyme, and tetraglyme. Among them, triglyme and tetraglyme are preferably used in terms of good yield, and the amount of triglyme and tetraglyme used is 5 to 200 times the weight of the ester compounds used in the reaction. Furthermore, if the solvent is inactive in the reaction, it may be mixed with the glyme-based solvent. Examples of solvents that can be mixed and used include aliphatic hydrocarbons such as pentane, hexane, and octane, aromatic hydrocarbons such as benzene, toluene, ethylbenzene, and xylene, ethers such as diethyl ether, diisopropyl ether, methyl-tert-butyl ether, methylcyclopentyl ether, and anisole, and halogenated aliphatic hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform.

[0017] The reaction temperature and time of the present invention are −100° C. to 0° C., and the reaction time is 1 hour to 48 hours. The post-treatment after the reaction in the present invention is not particularly limited and can be carried out by a known method. For example, after neutralization with dilute hydrochloric acid, the product is extracted with an organic solvent such as dichloromethane, dried with a drying agent such as anhydrous sodium sulfate, filtered, and concentrated to obtain the target product as a crude product, which may be further purified by silica gel column chromatography or the like to obtain a purified target product. EXAMPLES

[0018] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0019] The following instruments were used for the analysis: 1 H-NMR (300MHz), 19 F-NMR (282MHz), 13 C-NMR (125.8 MHz): Varian Mercury 300 and Bruker Avance 500. GC-MS: JEOL JMS-Q1050GC and Agilent7890. HRMS: Shimadzu GCMS-QP5050A (SHIMADZU GCMS-QP5050A). Infrared absorption (IR): JASCO FT / IR-4100 spectrometer (JASCO FT / IR-4100). Melting point: BUCHI M-565

[0020] In identifying the compounds, the data described in the following documents was used as a reference. Examples 1 to 6, 10 to 11, Comparative Examples 1 and 2: Xing Yi, Hui-Xiong Dai, Tetrahedron Lett., 2020, 61, 151780. Example 7: Xiao Xu, Feng Liu, Chem. Commun., 2018, 54, 11017. Example 8: Fengxiang Zhu, Xiao-Feng Wu, RSC Adv., 2016, 6, 57070. Example 9: Xiangyu Guo, Chao-Jun Li, Org. Lett., 2011, 13, 4977-4979. Example 12: Zhaomeng Han, Gongyong Li, Eur. J. Org. Chem., 2019, 4658-4661. Example 13: Christopher B. Kelly, Nicholas E, Eur. J. Org. Chem., 2015, 4071-4076. Example 14: James P. Phelan, Gary A. Molander, Chem. Sci., 2018, 9, 3215-3220. Examples 16 and 18: Pawel Czerwinski, Dr. Michal Michalak, Chem. Eur. J., 2016, 22, 8089-8094. Example 17: Pei Zhang, Chaozhong Li, Org. Lett., 2018, 20, 7062-7065. Examples 19-20 and 22: Xingguo Jiang, Denise Meyer, Dominik Baran, Miguel A. Corte's Gonza'lez, Ka'lma'n J. Szabo', J.Org.Chem., 2020, 85, 8311-8319. Example 21: Diego-Javier Barrios Antunez et al., Chem. Sci., 2019, 10, 6162-6173. Example 23: Trevor A. Hamlin et al., Eur. J. Org. Chem. 2013, 3658-3661.

[0021] Example 1 Preparation of 2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-one (a) [ka] Methyl 2-naphthoate (74.5 mg, 0.4 mmol) and triglyme (0.7 mL) were placed in a test tube equipped with a stirrer, and trifluoromethane (9.9 mL, 1.1 eq.) was added using a syringe while the container was cooled with liquid nitrogen. Next, a solution of potassium hexamethyldisilazide (160 mg, 0.8 mmol, 2.0 eq.) dissolved in triglyme (0.3 mL) was added to the test tube cooled to -40°C, and the reaction was carried out at the same temperature for 4 hours. After the reaction was completed, 1 M hydrochloric acid (1.0 mL) was added, and the aqueous layer was extracted with dichloromethane (1.0 mL x 3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. Trifluorotoluene was used as the internal standard substance. 19 The obtained crude product was analyzed by quantitative F-NMR, and it was found that the desired 2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-one (a) was obtained as a yellow solid (68.2 mg, 0.304 mmol, 76% yield).

[0022] The analytical results by NMR and GC-MS were as follows: 1 H-NMR (300MHz, CDCl3) δ: 8.61 (s, 1H), 8.07-7.88 (m, 4H), 7.71-7.58 (m, 2H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.22(s,3F)ppm. GC-MS(EI,m / z):127[M-COCF3] + (100%), 155[M-CF3] + (79%), 224[M] + (17%).

[0023] Examples 2 to 3 The same reaction apparatus as in Example 1 was used, and the various solvents shown in Table 1 were used instead of triglyme, and the reaction time was changed from 4 hours to overnight, but the same reaction procedure as in Example 1 was carried out to obtain the target 2,2,2-trifluoro-1-(naphthalene-2-yl)ethan-1-one (a). The results are shown in Table 1.

[0024] [Table 1]

[0025] Comparative Example 1 Preparation of 2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-one (a) The same reaction apparatus as in Example 1 was used, potassium tert-butoxide was used instead of potassium hexamethyldisilazide as the base, and the reaction time was changed from 4 hours to overnight. Except for this, the same reaction procedure as in Example 1 was carried out. The yield of the target 2,2,2-trifluoro-1-(naphthalene-2-yl)ethan-1-one was 29%.

[0026] Comparative Example 2 Preparation of 2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-one (a) The same reaction apparatus as in Example 1 was used, and potassium tert-butoxide was used instead of potassium hexamethyldisilazide as the base, toluene was used instead of triglyme as the solvent, and the reaction time was changed from 4 hours to overnight. Except for this, the same reaction procedure as in Example 1 was carried out, and the yield of the target 2,2,2-trifluoro-1-(naphthalen-2-yl)ethan-1-one (a) was 0%.

[0027] Example 4 Preparation of 2,2,2-trifluoro-1-(naphthalen-1-yl)ethan-1-one (b) [ka] Methyl 1-naphthoate (74.5 mg, 0.4 mmol) and triglyme (0.7 mL) were placed in a test tube equipped with a stirrer, and trifluoromethane (9.9 mL, 1.1 eq.) was added using a syringe while cooling the container with liquid nitrogen. Next, a solution of potassium hexamethyldisilazide (160 mg, 2.0 eq.) dissolved in triglyme (0.3 mL) was added to the test tube cooled to -40°C, and the reaction was carried out at the same temperature for 4 hours. After the reaction was completed, 1 M hydrochloric acid (1.0 mL) was added, and the aqueous layer was extracted with dichloromethane (1.0 mL x 3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The obtained crude product was subjected to silica gel column chromatography (n-hexane=100) to obtain the target 2,2,2-trifluoro-1-(naphthalene-1-yl)ethan-1-one (b) as a colorless transparent liquid (30.3 mg, 0.135 mmol, yield 34%).

[0028] The analytical results by NMR and GC-MS were as follows: 1 H-NMR (300MHz, CDCl3) δ:8.84(d,J=8.5Hz,1H),8.22-8.16(m,2H),7.95(d,J=7.9Hz,1H),7.74-7.57(m,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -70.63(s,3F)ppm. GC-MS(EI,m / z):127[M-COCF3] + (100%), 155[M-CF3] + (79%), 224[M] + (twenty one%).

[0029] Examples 5 to 18 Preparation of various trifluoromethyl ketones The same reaction apparatus as in Example 4 was used, and the same reaction procedure as in Example 4 was carried out, except that the ester compounds shown in Table 2 were used instead of methyl 1-naphthoate, to obtain the target trifluoromethyl ketones. The results are shown in Table 2, and the results of various analyses are described below.

[0030] [Table 2] TIFF0007623206000009.tif99145

[0031] 1) 1-(4-chlorophenyl)-2,2,2-trifluoroethan-1-one (c) The obtained crude product was purified with n-hexane / dichloromethane=1 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 8.01 (d, J = 8.2 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.98(s,3F)ppm. GC-MS(EI,m / z):111[M-COCF3] + ( 35 Cl, 57%), 113[M-COCF3] + ( 37 Cl, 15%), 139[M-CF3] + ( 35 Cl, 100%), 141 [M-CF3] + ( 37 Cl, 31%), 208[M] + ( 35 Cl, 6%), 210[M] + ( 37 Cl, 1%). 2) 1-(4-bromophenyl)-2,2,2-trifluoroethan-1-one (d) The obtained crude product was purified with n-hexane / dichloromethane=1 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 7.94 (d, J = 7.9 Hz, 2H), 7.71 (d, J = 8.8 Hz, 2H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-72.04(s,3F)ppm. GC-MS(EI,m / z):155[M-COCF3] + ( 79 Br, 49%), 157[M-COCF3] + ( 81 Br, 49%), 183 [M-CF3] + ( 79 Br, 100%), 185[M-CF3] + ( 81 Br, 96%), 252[M] + ( 79 Br, 13%), 254[M] + ( 81 Br, 12%). 3) 1-(4-iodophenyl)-2,2,2-trifluoroethan-1-one(e) The obtained crude product was purified with n-hexane / acetone=4 / 1 (vol / vol). Yellow solid. 1 H-NMR (300MHz, CDCl3) δ: 7.94 (d, J = 7.9 Hz, 2H), 7.76 (d, J = 7.9 Hz, 2H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-72.04(s,3F)ppm. GC-MS(EI,m / z):203[M-COCF3] + (35%), 231 [M-CF3] + (100%), 300[M] + (14%). 4) 1-[4-(tert-butyl)phenyl]-2,2,2-trifluoroethan-1-one (f) The obtained crude product was purified with n-hexane / dichloromethane=4 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3) δ:8.02(d,J=8.2Hz,2H),7.56(d,J=8.5Hz,2H),1.36(s,9H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.83(s,3F)ppm. HRMS(EI,m / z)C 12 H 13 OF3([M] + ) Calculated value: 230.0918, actual value: 230.0916. 5) 1-(4-cyclohexylphenyl)-2,2,2-trifluoroethan-1-one(g) The obtained crude product was purified with n-hexane / dichloromethane=9 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.01(d,J=7.9Hz,2H),7.38(d,J=8.2Hz,2H),2.61(s,1H),1.89-1.76(m,5H),1.51-1.26(m,5H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.76(s,3F)ppm. GC-MS(EI,m / z):187[M-CF3] + (100%). 6) 1-[(1,1'-biphenyl)-4-yl]-2,2,2-trifluoroethan-1-one(h) The obtained crude product was purified with n-hexane / diethyl ether=9 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3) δ:8.16(d,J=7.9Hz,2H),7.79-7.43(m,7H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.82(s,3F)ppm. GC-MS(EI,m / z):152[M-COCF3] + (79%), 181 [M-CF3] + (100%), 250[M] + (30%). 7) 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (i) The obtained crude product was purified with n-hexane / diethyl ether=9 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.06(d,J=8.5Hz,2H),7.01(d,J=9.1Hz,2H),3.92(s,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.47(s,3F)ppm. GC-MS(EI,m / z):135[M-CF3] + (82%), 152[M-CF3+OH] + (100%). 8) 1-(3-bromophenyl)-2,2,2-trifluoroethan-1-one(j) The obtained crude product was purified with n-hexane / dichloromethane=2 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.20(s,1H),8.01(d,J=7.3Hz,1H),7.85(d,J=8.8Hz,1H),7.45(t, J=7.9Hz,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.05(s,3F)ppm. GC-MS(EI,m / z):155[M-COCF3] + ( 79 Br, 68%), 157[M-COCF3] + ( 81 Br, 63%), 183[M-CF3] + ( 79 Br, 100%), 185[M-CF3] + ( 81 Br, 97%), 252[M] + ( 79 Br, 14%), 254[M] + ( 81 Br, 15%). 9) 2,2,2-Trifluoro-1-(3-iodophenyl)ethan-1-one(k) The obtained crude product was purified with n-hexane / ethyl acetate = 4 / 3 (vol / vol). yellow liquid. 1 H-NMR (300MHz, CDCl3) δ: 8.39 (s, 1H), 8.06-8.03 (m, 2H), 7.34-7.26 (m, 1H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-72.01(s,3F)ppm. GC-MS(EI,m / z):203[M-COCF3] + (49%), 231 [M-CF3] + (100%), 300[M] + (31%). 10) 1-(2-Bromophenyl)-2,2,2-trifluoroethan-1-one(l) The obtained crude product was purified with n-hexane / ethyl acetate = 5 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:7.77-7.70(m,2H),7.48-7.46(m,2H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -73.50(s,3F)ppm. GC-MS(EI,m / z):155[M-COCF3] + ( 79 Br, 51%), 157[M-COCF3] + ( 81 Br, 48%), 183 [M-CF3] + ( 79 Br, 100%), 185[M-CF3] + ( 81 Br,98%),252[M] + ( 79 Br, 5%), 254[M] + ( 81 Br,3%). 11) 2,2,2-Trifluoro-1-(2-iodophenyl)ethan-1-one(m) The obtained crude product was purified with n-hexane / dichloromethane=4 / 3 (vol / vol). Yellow solid. 1 H-NMR (300MHz, CDCl3)δ:8.09(d,J=7.6Hz,1H),7.74(d,J=6.7Hz,1H),7.51(t,J=7.6Hz,1H),7.29(t,J=7.6Hz,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.77(s,3F)ppm. 13 C-NMR (126MHz, CDCl3) δ: 182.4 (q, J = 35.7 Hz), 142.4, 134.3, 130.2, 130.1, 128.1, 115.5 (q, J = 292.1 Hz), 94.0 ppm. ATR-FTIR(KBr):ν=3431,3092,1469,1432,1323,1279,1052,1020,792,755,698,676,637,460,422cm- 1 Melting point: 40.2-40.7℃ HRMS (EI, m / z) C8H4OF3I ([M] + ) Calculated value: 299.9259, actual value: 299.9261. 12) 1-(3,4-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one(n) The obtained crude product was purified with n-hexane / diethyl ether=9 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3) δ:7.74(d,J=8.2Hz,1H),7.58(s,1H),6.96(d,J=8.5Hz,1H),4.00(s,3H),3.96(s,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -70.90(s,3F)ppm. GC-MS(EI,m / z):165[M-CF3] + (100%), 234[M] + (51%). 13) 1-[(3r,5r,7r)-adamantan-1-yl]-2,2,2-trifluoroethan-1-one(o) The obtained crude product was purified with n-hexane / ethyl acetate = 9 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 3.65 (s, 2H), 2.09-1.67 (m, 13H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.66(s,3F)ppm. GC-MS(EI,m / z):135[M-COCF3] + (100%). 14) (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one (p) The obtained crude product was purified with n-hexane / dichloromethane=10 / 1 (vol / vol). yellow liquid. 1 H-NMR(300MHz,CDCl3)δ:7.97(d,J=15.8Hz,1H),7.64(d,J=6.7Hz,2H),7.50-7.43(m,3H),7.02(d,J=15.8Hz,1H) 19 F-NMR (282MHz, CDCl3)δ: -78.05(s,3F)ppm. GC-MS(EI,m / z):103[M-COCF3] + (79%), 131 [M-CF3] + (100%), 200[M] + (39%).

[0032] Example 19 Preparation of 2,2,3,3,3-pentafluoro-1-(naphthalen-2-yl)propan-1-one (q) [ka] Potassium hexamethyldisilazide (79.8 mg, 0.4 mmol, 2.0 eq.) and triglyme (1.0 mL) were charged into a Schlenk tube equipped with a stirrer, and pentafluoroethane (excess amount) was added while cooling the container with liquid nitrogen. The Schlenk tube was then heated to -40°C, and a solution of 1-naphthoic acid methyl ester (37.2 mg, 0.2 mmol) dissolved in triglyme was added to the Schlenk tube, and the reaction was carried out at the same temperature. After the reaction was completed, a saturated aqueous ammonium chloride solution (1.0 mL) was added, and the aqueous layer was extracted with diethyl ether (1.0 mL x 3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The obtained crude product was purified by silica gel column chromatography (n-hexane / ethyl acetate = 98 / 2 (vol / vol)) to obtain the target 2,2,3,3,3-pentafluoro-1-(naphthalen-2-yl)propan-1-one (q) as a colorless transparent liquid (35.1 mg, 0.128 mmol, yield 64%).

[0033] The analytical results by NMR and GC-MS were as follows: 1 H-NMR (300MHz, CDCl3) δ: 8.67 (s, 1H), 8.00 (m, 4H), 7.66 (m, 2H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-82.00(s,3F),-115.33(s,2F)ppm. HRMS (EI, m / z) C13H7OF5 ([M]+) calculated: 274.0417, found: 274.0417.

[0034] Examples 20 to 23 Preparation of various pentafluoroethyl ketones The same reaction apparatus as in Example 19 was used, and the same reaction procedure as in Example 19 was carried out, except that the ester compounds shown in Table 3 were used instead of methyl 1-naphthoate, to obtain the target pentafluoroethyl ketones. The results are shown in Table 3, and the results of various analyses are described below.

[0035] [Table 3]

[0036] 15) 1-(4-Methoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one (r) The obtained crude product was purified with n-hexane / ethyl acetate = 98 / 2 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.08(d,J=8.1Hz,2H),7.00(d,J=9.1Hz,2H),3.92(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-82.11(s,3F),-115.65(s,2F)ppm. HRMS (EI, m / z) C10H7O2F5 ([M]+) calculated: 254.0366, found: 254.0362. 16) 1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one(s) The obtained crude product was purified with n-hexane = 100%. Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 7.96 (d, J = 8.8 Hz, 2H), 7.71 (dd, J = 8.7, 2.1 Hz, 2H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-82.06(s,3F),-116.19(s,2F)ppm. HRMS (EI, m / z) C9H4OF5Br ([M]+) calculated: 301.9366, found: 301.9362. 17) 1-[(1,1'-biphenyl)-4-yl]-2,2,3,3,3-pentafluoropropan-1-one (t) The obtained crude product was purified with n-hexane / ethyl acetate = 98 / 2 (vol / vol). Colorless transparent liquid. 1H-NMR (300MHz, CDCl3) δ:8.15(d,J=7.3Hz,2H),7.76-7.43(m,7H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-82.97(s,3F),-115.88(s,2F)ppm. HRMS (EI, m / z) C15H9OF5 ([M]+) calculated: 300.0574, found: 300.0570. 18) (E)-1,1,1,2,2-Pentafluoro-5-phenylpent-4-en-3-one (u) The obtained crude product was purified with n-hexane / ethyl acetate = 95 / 5 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.00(d,J=15.5Hz,1H),7.66(d,J=7.9Hz,2H),7.52-7.43(m,3H),7.13(d,J=15.8Hz,1H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-82.48(s,3F),-124.26(s,2F)ppm. HRMS (EI, m / z) C11H7OF5 ([M]+) calculated: 250.0417, found: 250.0421. [Industrial Applicability]

[0037] The trifluoromethyl ketones obtained by the method of the present invention are useful as intermediates in the production of pharmaceuticals, agricultural chemicals, electronic materials, and the like.

Claims

1. The following general formula (1) 【Chemistry 8】 [In formula (1), R １ represents a naphthyl-1-yl group, a naphthyl-2-yl group, or a 1-adamantyl group; R ２ represents a methyl group or an ethyl group. The present invention relates to a method for producing an ester compound represented by the following general formula (3): 【Chemistry 10】 [In formula (3), Rf represents a trifluoromethyl group or a pentafluoroethyl group, and R １ represents a naphthyl-1-yl group, a naphthyl-2-yl group, or a 1-adamantyl group. A method for producing a trifluoromethyl ketone or a pentafluoroethyl ketone represented by the following formula:

2. 2. The method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to claim 1, wherein the glyme-based solvent is triglyme and / or tetraglyme.

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