Method for producing trifluoromethyl ketones and pentafluoroethyl ketones

Abstract

To provide methods for producing trifluoromethyl ketone and pentafluoroethyl ketone in economical, safe and industrial manners.SOLUTION: An ester compound represented by the general formula (1) is supplied and mixed with a base and trifluoromethane or pentafluoroethane in the presence of organic solvent by using a micro mixer and a micro reactor, and the reaction of them results in a trifluoromethyl ketone or pentafluoroethyl ketone represented by the general formula (3). [R1 is a naphthyl-1-yl group or the like; R2 is a methyl group or an ethyl group; Rf is a trifluoromethyl group or pentafluoroethyl group].SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing trifluoromethyl ketones or pentafluoroethyl ketones from ester compounds by generating trifluoromethyl anions or pentafluoroethyl anions using trifluoromethane (also known as fluoroform, hereinafter referred to as "trifluoromethane") or pentafluoroethane as raw materials. 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 for producing trifluoromethyl ketones by reacting trifluoromethane with esters has been known (Non-Patent Document 1). Also known is a method of producing pentafluoroethyl group-containing alcohols by reacting pentafluoroethane with a carbonyl compound such as a ketone or an aldehyde (Non-Patent Document 2). Furthermore, a method is known in which pentafluoroethane is reacted with a carbonyl compound such as a ketone or an aldehyde in a continuous reaction system using a flow microreactor to produce alcohols containing a pentafluoroethyl group (Non-Patent Document 3).

[0003] The conventional method described in Non-Patent Document 1 is a batch reaction, and requires cooling the reaction temperature to -40°C. When carried out on an industrial scale, maintaining the inside of a reaction vessel at -40°C is extremely costly, and therefore a reaction that does not require such a low temperature of -40°C is desired. Furthermore, the method described in Non-Patent Document 2 relates to the reaction of pentafluoroethane with a carbonyl compound such as a ketone or an aldehyde, and does not describe the reaction of pentafluoroethane with carboxylic acid esters of the present invention. Furthermore, the method described in Non-Patent Document 3 is a reaction in a continuous reaction system using a flow microreactor, but does not describe the reaction of pentafluoroethane with carboxylic acid esters of the present invention. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Fujihira, Y. et al., Beilstein J. Org. Chem. 2021, 17, 431. [Non-patent document 2] Fujihira, Y. et al., J.Org.Chem.2021,86,5883. [Non-patent document 3] Ono, M. et al., J.Org.Chem.2021,86,5883. Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a practical production method, i.e., an economical, safe and industrial production method, in which trifluoromethyl ketones or pentafluoroethyl ketones are obtained by reacting trifluoromethane or pentafluoroethane as a raw material with a base and an ester compound in an organic solvent. [Means for solving the problem]

[0006] The present inventors have conducted extensive research into a method for obtaining trifluoromethyl ketones or pentafluoroethyl ketones from ester compounds using trifluoromethane or pentafluoroethane as a raw material, and as a result have found that by using a micromixer and a microreactor to instantaneously mix trifluoromethane or pentafluoroethane, a base, and an ester compound in a short time of 1.0 second or less, it is not necessary to maintain a low temperature as compared with a batch reaction, and the target trifluoromethyl ketones or pentafluoroethyl ketones can be obtained in good yield, thereby completing the present invention.

[0007] That is, the present invention relates to the following inventions. [1] The following general formula (1) [ka] [In formula (1), R 1 is a naphthyl-1-yl group, a naphthyl-2-yl group, a styryl group, 1-methylindol-2-yl, 1-benzofuran-2-yl, 1-benzo[b]thiophen-2-yl, 2-(4-chlorophenoxy)propan-2-yl, 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 C1-C4 alkyl group, a cyclohexyl group, a methoxy group, an ethoxy group, a dimethylamino group, a diethylamino group, a nitro group, a benzyloxy group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, a dipropylaminosulfonyl 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 styryl group, 1-methylindol-2-yl, 1-benzofuran-2-yl, 1-benzo[b]thiophen-2-yl, 2-(4-chlorophenoxy)propan-2-yl, or a group represented by the following general formula (2): [ka] (In formula (2), R 3 and R 4each independently represents a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a cyclohexyl group, a methoxy group, an ethoxy group, a dimethylamino group, a diethylamino group, a nitro group, a benzyloxy group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, a dipropylaminosulfonyl group, or a phenyl group). The present invention provides a method for producing trifluoromethyl ketones or pentafluoroethyl ketones represented by the following formula: In addition, when an ester compound is mixed in the presence of an organic solvent by supplying a base and trifluoromethane or pentafluoroethane to a micromixer and a microreactor, or to a microreactor, and mixing is performed by the micromixer, and if necessary, by mixing by a microreactor without using a micromixer, the mixing may be performed continuously, discontinuously, for example, by pausing, or sequentially. [2] The method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to [1], wherein the organic solvent is triglyme. [3] A method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to [1] or [2], characterized in that the trifluoromethyl group or pentafluoroethyl group substitution reaction of the ester compounds represented by formula (1) is carried out at -30°C to 40°C. [4] The method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to any one of [1] to [3], wherein the base is potassium hexamethyldisilazide and / or potassium tert-butoxide, and is used in an amount of 1.0 to 5.0 molar equivalents relative to the ester compound represented by formula (1). [5] The method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to any one of [1] to [4], characterized in that the mixing time of the ester compound, the base, and the trifluoromethane or pentafluoroethane in the micromixer is in the range of 0.001 seconds to 1 second. [6] The method for producing trifluoromethyl ketones or pentafluoroethyl ketones according to any one of [1] to [5], characterized in that a micromixer having a structure capable of simultaneously mixing three components is used.

[0008] Trifluoromethyl ketones or pentafluoroethyl ketones represented by the above formula (3) exist in equilibrium between the ketone body and the ketone hydrate. The ketone body is hydrated by the moisture contained in the air or the solution. On the other hand, the ketone hydrate can be converted into the ketone body by azeotropic dehydration using benzene, toluene, heptane, etc. Therefore, the trifluoromethyl ketones or pentafluoroethyl ketones represented by formula (3) include trifluoromethyl ketone hydrates or pentafluoroethyl ketone hydrates, and their equilibrium mixtures. [Effects of the Invention]

[0009] The present invention provides a method that enables trifluoromethylation or pentafluoroethylation of ester compounds using trifluoromethane or pentafluoroethane as a raw material to be carried out under mild conditions. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a diagram showing an example of a microflow reactor embodying the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described in detail below. An apparatus applicable to the present invention is a continuous reaction apparatus comprising a metering pump for supplying a predetermined amount of an ester compound solution and a base solution, a mass flow controller for supplying a predetermined amount of trifluoromethane or pentafluoroethane as a gas, a micromixer for mixing the ester compound solution, the base solution, and trifluoromethane or pentafluoroethane, and a microreactor for reacting the mixture, and into which a predetermined amount of each reagent is continuously supplied to carry out the reaction. The reaction may be carried out using a three-component mixing micromixer, or a two-component mixing micromixer in which the base and ester compound are mixed in advance and then reacted with trifluoromethane or pentafluoroethane.

[0012] In the present invention, the C1-C4 alkyl group includes a linear or branched alkyl group, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.

[0013] 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 the methyl group is a methyl group include methyl 1-naphthoate, methyl 2-naphthoate, methyl (E)-3-phenylacrylate, methyl 1-methylindole-2-carboxylate, methyl 1-methylindole-3-carboxylate, methyl 1-benzofuran-2-carboxylate, methyl 1-benzofuran-3-carboxylate, methyl 1-benzo[b]thiophene-2-carboxylate, methyl 1-benzo[b]thiophene-3-carboxylate, methyl 2-(4-chlorophenoxy)-2-methylpropionate, methyl benzoate, methyl 2-fluorobenzoate, methyl 3-benzo[b]thiophene-2-carboxylate, methyl 2-(4-chlorophenoxy)-2-methylpropionate, methyl benzoate, methyl 2-fluorobenzoate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 2-(4-chlorophenoxy)-2-methylpropionate, methyl benzoate, methyl 2-fluorobenzoate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 2-(4-chlorophenoxy)-2-methylpropionate, methyl 3-benzo[b]thiophene-3-carboxylate ...3-benzo[b]thiophene-3-carboxylate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 3-benzo[b]thiophene-3-carboxylate, methyl 3-benzo Methyl -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-propylbenzoic acid Methyl, 4-n-propylbenzoate, methyl 2-isopropylbenzoate, methyl 3-isopropylbenzoate, methyl 4-isopropylbenzoate, methyl 2-n-butylbenzoate, methyl 3-n-butylbenzoate, methyl 4-n-butylbenzoate, methyl 2-isobutylbenzoate, methyl 3-isobutylbenzoate, methyl 4-isobutylbenzoate, methyl 2-sec-butylbenzoate, methyl 3-sec-butylbenzoate, methyl 4-sec-butylbenzoate, methyl 2-tert-butylbenzoate, methyl 3-tert-butylbenzoate, 4-ter Methyl t-butylbenzoate, methyl 2-cyclohexylbenzoate, methyl 3-cyclohexylbenzoate, methyl 4-cyclohexylbenzoate, methyl 2-methoxybenzoate, methyl 3-methoxybenzoate, methyl 4-methoxybenzoate, methyl 2-ethoxybenzoate, methyl 3-ethoxybenzoate, methyl 4-ethoxybenzoate, methyl 2-dimethylaminobenzoate, methyl 3-dimethylaminobenzoate, methyl 4-dimethylaminobenzoate, methyl 2-diethylaminobenzoate, methyl 3-methylaminobenzoate, methyl 4-methylaminobenzoate,Methyl 2-nitrobenzoate, Methyl 3-nitrobenzoate, Methyl 4-nitrobenzoate, Methyl 2-benzyloxybenzoate, Methyl 3-benzyloxybenzoate, Methyl 4-benzyloxybenzoate, Methyl 2-dimethylaminosulfonylbenzoate, Methyl 3-dimethylaminosulfonylbenzoate, Methyl 4-dimethylaminosulfonylbenzoate, Methyl 2-diethylaminosulfonylbenzoate, Methyl 3-diethylaminosulfonylbenzoate, Methyl 4-diethylaminosulfonylbenzoate, Methyl 2-di-n-propylaminosulfonylbenzoate , methyl 3-di-n-propylaminosulfonylbenzoate, methyl 4-di-n-propylaminosulfonylbenzoate, methyl 2-di(isopropyl)aminosulfonylbenzoate, methyl 3-di(isopropyl)aminosulfonylbenzoate, methyl 4-di(isopropyl)aminosulfonylbenzoate, 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, 3,4 -Methyl 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, methyl 3,5-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, 2,4-diiodo Methyl benzoate, methyl 2,5-diiodobenzoate, methyl 2,6-diiodobenzoate, methyl 3,4-diiodobenzoate, methyl 3,5-diiodobenzoate, methyl 2,3-dimethylbenzoate, methyl 2,4-dimethylbenzoate, methyl 2,5-dimethylbenzoate, 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-diisopropylbenzoate, Methyl 2,4-diisopropylbenzoate, Methyl 2,5-diisopropylbenzoate, Methyl 2,6-diisopropylbenzoate, Methyl 3,4-diisopropylbenzoate, 3,5-diisopropylbenzoic acid Methyl, 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, methyl 3,5-di-n-butylbenzoate, methyl 2,3-diisobutylbenzoate, methyl 2,4-diisobutylbenzoate, methyl 2,5-diisobutylbenzoate, methyl 2,6-diisobutylbenzoate, methyl 3,4-diisobutylbenzoate, methyl 3,5-diisobutylbenzoate, methyl 2,3-di-sec-butylbenzoate, Methyl 2,4-di-sec-butylbenzoate, methyl 2,5-di-sec-butylbenzoate, methyl 2,6-di-sec-butylbenzoate, methyl 3,4-di-sec-butylbenzoate, methyl 3,5-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, 2,3-dicyclohexyl methyl 2,4-dicyclohexylbenzoate, methyl 2,5-dicyclohexylbenzoate, methyl 2,6-dicyclohexylbenzoate, methyl 3,4-dicyclohexylbenzoate, 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, Methyl 3,5-diethoxybenzoate, Methyl 2,3-bis(dimethylamino)benzoate, Methyl 2,4-bis(dimethylamino)benzoate, Methyl 2,5-bis(dimethylamino)benzoate, Methyl 2,6-bis(dimethylamino)benzoate, Methyl 3,4-bis(dimethylamino)benzoate, Methyl 3,5-bis(dimethylamino)benzoate, Methyl 2,3-bis(diethylamino)benzoate, Methyl 2,4-bis(diethylamino) ) methyl benzoate, methyl 2,5-bis(diethylamino)benzoate, methyl 2,6-bis(diethylamino)benzoate, methyl 3,4-bis(diethylamino)benzoate, methyl 3,5-bis(diethylamino)benzoate, methyl 2,3-dinitrobenzoate, methyl 2,4-dinitrobenzoate, methyl 2,5-dinitrobenzoate, methyl 2,6-dinitrobenzoate, methyl 3,4-dinitrobenzoate, methyl 3,5-dinitrobenzoate, methyl 2,3-di(benzyloxy)benzoate, methyl 2,4-di(benzyloxy)benzoate, 2, Methyl 5-di(benzyloxy)benzoate, Methyl 2,6-di(benzyloxy)benzoate, Methyl 3,4-di(benzyloxy)benzoate, Methyl 3,5-di(benzyloxy)benzoate, Methyl 2,3-bis(dimethylaminosulfonyl)benzoate, Methyl 2,4-bis(dimethylaminosulfonyl)benzoate, Methyl 2,5-bis(dimethylaminosulfonyl)benzoate, Methyl 2,6-bis(dimethylaminosulfonyl)benzoate, Methyl 3,4-bis(dimethylaminosulfonyl)benzoate, Methyl 3,5-bis(dimethylaminosulfonyl)benzoate methyl 2,3-bis(diethylaminosulfonyl)benzoate, methyl 2,4-bis(diethylaminosulfonyl)benzoate, methyl 2,5-bis(diethylaminosulfonyl)benzoate, methyl 2,6-bis(diethylaminosulfonyl)benzoate, methyl 3,4-bis(diethylaminosulfonyl)benzoate, methyl 3,5-bis(diethylaminosulfonyl)benzoate, methyl 2,3-bis(di-n-propylaminosulfonyl)benzoate, methyl 2,4-bis(di-n-propylaminosulfonyl)benzoate,Methyl 2,5-bis(di-n-propylaminosulfonyl)benzoate, Methyl 2,6-bis(di-n-propylaminosulfonyl)benzoate, Methyl 3,4-bis(di-n-propylaminosulfonyl)benzoate, Methyl 3,5-bis(di-n-propylaminosulfonyl)benzoate, Methyl 2,3-bis(di[isopropyl]aminosulfonyl)benzoate, Methyl 2,4-bis(di[isopropyl]aminosulfonyl)benzoate, Methyl 2,5-bis(di[isopropyl]aminosulfonyl)benzoate, Methyl 2,6-bis(di[isopropyl]aminosulfonyl)benzoate, Methyl 3,4-bis(di[isopropyl]aminosulfonyl)benzoate, Methyl 3,5-bis(di[isopropyl]amino sulfonyl)benzoate, methyl 2,3-diphenylbenzoate, methyl 2,4-diphenylbenzoate, methyl 2,5-diphenylbenzoate, methyl 2,6-diphenylbenzoate, methyl 3,4-diphenylbenzoate, methyl 3,5-diphenylbenzoate, methyl 2-chloro-3-nitrobenzoate, methyl 2-chloro-4-nitrobenzoate, methyl 2-chloro-5-nitrobenzoate, methyl 2-chloro-6-nitrobenzoate, methyl 3-chloro-2-nitrobenzoate, methyl 3-chloro-4-nitrobenzoate, methyl 3-chloro-5-nitrobenzoate, methyl 5-chloro-2-nitrobenzoate, methyl 4-chloro-2-nitrobenzoate, methyl 4-chloro-3-nitrobenzoate, and the like.

[0014] The ester compounds represented by the general formula (1) applicable to the present invention are 2Specific examples of those in which the ethyl group is an ethyl group include ethyl 1-naphthoate, ethyl 2-naphthoate, ethyl (E)-3-phenylacrylate, ethyl 1-methylindole-2-carboxylate, ethyl 1-methylindole-3-carboxylate, ethyl 1-benzofuran-2-carboxylate, ethyl 1-benzofuran-3-carboxylate, ethyl 1-benzo[b]thiophene-2-carboxylate, ethyl 1-benzo[b]thiophene-3-carboxylate, ethyl 2-(4-chlorophenoxy)-2-methylpropionate, ethyl benzoate, ethyl 2-fluorobenzoate, ethyl 3-benzo[b]thiophene-2-carboxylate, ethyl 2-(4-chlorophenoxy)-2-methylpropionate, ethyl benzoate, ethyl 2-fluorobenzoate, ethyl 3-benzo[b]thiophene-3-carboxylate, ethyl 2-(4-chlorophenoxy)-2-methylpropionate, ethyl 3-benzo[b]thiophene-3-carboxylate, ethyl 3-benzo[b]thiophene-3-carboxylate, ethyl 3-benzo[b]thiophene-2-carboxylate, ethyl 3-benzo[b]thiophene-3 ... Ethyl -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-propylbenzoic acid Ethyl, 4-n-propylbenzoate, ethyl 2-isopropylbenzoate, ethyl 3-isopropylbenzoate, ethyl 4-isopropylbenzoate, ethyl 2-n-butylbenzoate, ethyl 3-n-butylbenzoate, ethyl 4-n-butylbenzoate, ethyl 2-isobutylbenzoate, ethyl 3-isobutylbenzoate, ethyl 4-isobutylbenzoate, ethyl 2-sec-butylbenzoate, ethyl 3-sec-butylbenzoate, ethyl 4-sec-butylbenzoate, ethyl 2-tert-butylbenzoate, ethyl 3-tert-butylbenzoate, 4-ter Ethyl t-butylbenzoate, ethyl 2-cyclohexylbenzoate, ethyl 3-cyclohexylbenzoate, ethyl 4-cyclohexylbenzoate, ethyl 2-methoxybenzoate, ethyl 3-methoxybenzoate, ethyl 4-methoxybenzoate, ethyl 2-ethoxybenzoate, ethyl 3-ethoxybenzoate, ethyl 4-ethoxybenzoate, ethyl 2-dimethylaminobenzoate, ethyl 3-dimethylaminobenzoate, ethyl 4-dimethylaminobenzoate, ethyl 2-diethylaminobenzoate, ethyl 3-methylaminobenzoate, ethyl 4-methylaminobenzoate,Ethyl 2-nitrobenzoate, Ethyl 3-nitrobenzoate, Ethyl 4-nitrobenzoate, Ethyl 2-benzyloxybenzoate, Ethyl 3-benzyloxybenzoate, Ethyl 4-benzyloxybenzoate, Ethyl 2-dimethylaminosulfonylbenzoate, Ethyl 3-dimethylaminosulfonylbenzoate, Ethyl 4-dimethylaminosulfonylbenzoate, Ethyl 2-diethylaminosulfonylbenzoate, Ethyl 3-diethylaminosulfonylbenzoate, Ethyl 4-diethylaminosulfonylbenzoate, Ethyl 2-di-n-propylaminosulfonylbenzoate , ethyl 3-di-n-propylaminosulfonylbenzoate, ethyl 4-di-n-propylaminosulfonylbenzoate, ethyl 2-di(isopropyl)aminosulfonylbenzoate, ethyl 3-di(isopropyl)aminosulfonylbenzoate, ethyl 4-di(isopropyl)aminosulfonylbenzoate, 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, 3,4 -Ethyl 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 3,5-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, 2,4-diiodo Ethyl benzoate, 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 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-diisopropylbenzoate, Ethyl 2,4-diisopropylbenzoate, Ethyl 2,5-diisopropylbenzoate, Ethyl 2,6-diisopropylbenzoate, Ethyl 3,4-diisopropylbenzoate, Ethyl 3,5-diisopropylbenzoic acid Ethyl, 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 3,5-di-n-butylbenzoate, ethyl 2,3-diisobutylbenzoate, ethyl 2,4-diisobutylbenzoate, ethyl 2,5-diisobutylbenzoate, ethyl 2,6-diisobutylbenzoate, ethyl 3,4-diisobutylbenzoate, ethyl 3,5-diisobutylbenzoate, 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 3,5-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, 2,3-dicyclohexyl Ethyl 2,4-dicyclohexylbenzoate, ethyl 2,5-dicyclohexylbenzoate, ethyl 2,6-dicyclohexylbenzoate, ethyl 3,4-dicyclohexylbenzoate, 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, Ethyl 3,5-diethoxybenzoate, Ethyl 2,3-bis(dimethylamino)benzoate, Ethyl 2,4-bis(dimethylamino)benzoate, Ethyl 2,5-bis(dimethylamino)benzoate, Ethyl 2,6-bis(dimethylamino)benzoate, Ethyl 3,4-bis(dimethylamino)benzoate, Ethyl 3,5-bis(dimethylamino)benzoate, Ethyl 2,3-bis(diethylamino)benzoate, Ethyl 2,4-bis(diethylamino) ) ethyl benzoate, ethyl 2,5-bis(diethylamino)benzoate, ethyl 2,6-bis(diethylamino)benzoate, ethyl 3,4-bis(diethylamino)benzoate, ethyl 3,5-bis(diethylamino)benzoate, ethyl 2,3-dinitrobenzoate, ethyl 2,4-dinitrobenzoate, ethyl 2,5-dinitrobenzoate, ethyl 2,6-dinitrobenzoate, ethyl 3,4-dinitrobenzoate, ethyl 3,5-dinitrobenzoate, ethyl 2,3-di(benzyloxy)benzoate, ethyl 2,4-di(benzyloxy)benzoate, 2, Ethyl 5-di(benzyloxy)benzoate, Ethyl 2,6-di(benzyloxy)benzoate, Ethyl 3,4-di(benzyloxy)benzoate, Ethyl 3,5-di(benzyloxy)benzoate, Ethyl 2,3-bis(dimethylaminosulfonyl)benzoate, Ethyl 2,4-bis(dimethylaminosulfonyl)benzoate, Ethyl 2,5-bis(dimethylaminosulfonyl)benzoate, Ethyl 2,6-bis(dimethylaminosulfonyl)benzoate, Ethyl 3,4-bis(dimethylaminosulfonyl)benzoate, Ethyl 3,5-bis(dimethylaminosulfonyl)benzoate ethyl 2,3-bis(diethylaminosulfonyl)benzoate, ethyl 2,4-bis(diethylaminosulfonyl)benzoate, ethyl 2,5-bis(diethylaminosulfonyl)benzoate, ethyl 2,6-bis(diethylaminosulfonyl)benzoate, ethyl 3,4-bis(diethylaminosulfonyl)benzoate, ethyl 3,5-bis(diethylaminosulfonyl)benzoate, ethyl 2,3-bis(di-n-propylaminosulfonyl)benzoate, ethyl 2,4-bis(di-n-propylaminosulfonyl)benzoate,Ethyl 2,5-bis(di-n-propylaminosulfonyl)benzoate, Ethyl 2,6-bis(di-n-propylaminosulfonyl)benzoate, Ethyl 3,4-bis(di-n-propylaminosulfonyl)benzoate, Ethyl 3,5-bis(di-n-propylaminosulfonyl)benzoate, Ethyl 2,3-bis(di[isopropyl]aminosulfonyl)benzoate, Ethyl 2,4-bis(di[isopropyl]aminosulfonyl)benzoate, Ethyl 2,5-bis(di[isopropyl]aminosulfonyl)benzoate, Ethyl 2,6-bis(di[isopropyl]aminosulfonyl)benzoate, Ethyl 3,4-bis(di[isopropyl]aminosulfonyl)benzoate, Ethyl 3,5-bis(di[isopropyl]amino Examples of the methyl benzoate include ethyl 2,3-diphenylbenzoate, ethyl 2,4-diphenylbenzoate, ethyl 2,5-diphenylbenzoate, ethyl 2,6-diphenylbenzoate, ethyl 3,4-diphenylbenzoate, ethyl 3,5-diphenylbenzoate, ethyl 2-chloro-3-nitrobenzoate, ethyl 2-chloro-4-nitrobenzoate, ethyl 2-chloro-5-nitrobenzoate, ethyl 2-chloro-6-nitrobenzoate, ethyl 3-chloro-2-nitrobenzoate, ethyl 3-chloro-4-nitrobenzoate, ethyl 3-chloro-5-nitrobenzoate, ethyl 5-chloro-2-nitrobenzoate, ethyl 4-chloro-2-nitrobenzoate, and ethyl 4-chloro-3-nitrobenzoate.

[0015] Specific examples of the trifluoromethyl ketones represented by the general formula (3) that can be produced by the present invention include 1-(naphthalen-1-yl)-2,2,2-trifluoroethan-1-one, 1-(naphthalen-2-yl)-2,2,2-trifluoroethan-1-one, (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one, 1-(1-methylindol-2-yl)-2,2,2-trifluoroethan-1-one, 1-(1-methylindol-3-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzofuran-2-yl)-2,2,2-trifluoroethan-1-one, 1-(1-methylindol-3-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzofuran-2-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzofuran-3 ... -2-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzofuran-3-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzo[b]thiophen-2-yl)-2,2,2-trifluoroethan-1-one, 1-(1-benzo[b]thiophen-3-yl)-2,2,2-trifluoroethan-1-one, 3-(4-chlorophenoxy)-1,1,1-trifluoro-3-methylbutan-2-one, 1-phenyl-2,2,2-trifluoroethan-1-one, 1-(2-fluorophenyl)-2,2,2 -trifluoroethan-1-one, 1-(3-fluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-fluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-chlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-chlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-chlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-bromophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-bromophenyl)-2,2 ,2-trifluoroethan-1-one, 1-(4-bromophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-iodophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-iodophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-iodophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-methylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3-methylphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-methylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-ethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3-ethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-ethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[n-propyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[n-propyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[n-propyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-isopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3-isopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-isopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[n-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[n-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[n-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-isobutylphenyl) 1-(3-isobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-isobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[sec-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[sec-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[sec-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[tert-butyl]phenyl)-2,2,2-trifluoroethan-1-one )-2,2,2-trifluoroethan-1-one, 1-(3-[tert-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[tert-butyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-cyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3-cyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-cyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-methoxyphenyl)-2,2,2-Trifluoroethan-1-one, 1-(3-methoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-methoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-ethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(3-ethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(4-ethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2-dimethylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-diaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(methylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-dimethylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-diethylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-diethylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-diethylaminophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-nitrophenyl)-2,2, 2-Trifluoroethan-1-one, 1-(4-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[dimethylaminosulfonyl]phenyl)- nyl)-2,2,2-trifluoroethan-1-one, 1-(4-[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[di-n-propylaminosulfonyl]phenyl)-2,2,2-Trifluoroethan-1-one, 1-(3-[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2-[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3-[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(4-[diisopropylaminosulfonyl]phenyl)-2,2, 2-Trifluoroethan-1-one, 1-([1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1'-biphenyl]-3-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-one, 1-(2,3-difluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-difluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-difluorophenyl)-2,2,2- Trifluoroethan-1-one, 1-(2,6-difluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-difluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-difluorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1 -(2,6-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-dibromophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-dibromophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dibromophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-dibromophenyl)-2,2,2-Trifluoroethan-1-one, 1-(3,4-dibromophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dibromophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-diiodophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-diiodophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-diiodophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-diiodophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-diiodophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-diiodophenyl)-2,2,2-trifluoroethan-1-one 1-(2,3-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dimethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-diethylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-di-n-propylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-di-n-propylphenyl)- 1-(2,5-di-n-propylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-di-n-propylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-di-n-propylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-di-n-propylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-diisopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-diisopropylphenyl)-2,2,2-trifluoroethan-1-one 1-(2,5-diisopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-diisopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-diisopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-diisopropylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one )-2,2,2-trifluoroethan-1-one, 1-(2,5-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-di-n-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-diisobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-diisobutylphenyl)-2,2,2-Trifluoroethan-1-one, 1-(2,5-diisobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-diisobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-diisobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-diisobutylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-di-sec-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-di-sec-butylphenyl)-2,2,2- Trifluoroethan-1-one, 1-(2,5-di-sec-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-di-sec-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-di-sec-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-di-sec-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-di-tert-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-di-tert-butylphenyl)- 1-(2,5-di-tert-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-di-tert-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-di-tert-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-di-tert-butylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2, 4-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dicyclohexylphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-diethoxyphenyl) -2,2,2-trifluoroethan-1-one, 1-(2,4-diethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-diethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-diethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-diethoxyphenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-diethoxyphenyl)-2,2,2-trifluoroethan-1-one Ethan-1-one, 1-(2,3-bis[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[dimethylamino] phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[diethylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one 1-(2,6-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[di-n-propylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one ]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[diisopropylamino]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-dinitrophenyl)-2,2,2-trifluoroethan-1-one 1-(2,4-dinitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-dinitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-dinitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-dinitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-dinitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-di[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[dimethylaminosulfonyl]phenyl)-2 ,2,2-trifluoroethan-1-one, 1-(2,4-bis[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[dimethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[dimethylaminosulfonyl]phenyl) 1-(2,3-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[diethylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,5-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[di-n-propylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,3-bis[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,4-bis[diisopropylaminosulfonyl]phenyl)-2 ,2,2-trifluoroethan-1-one, 1-(2,5-bis[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(2,6-bis[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,4-bis[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-(3,5-bis[diisopropylaminosulfonyl]phenyl)-2,2,2-trifluoroethan-1-one, 1-([1,1',2', 1-([1,1',2',1''-terphenyl]-3'-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1',2',1''-terphenyl]-4'-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1',3',1''-terphenyl]-2'-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1',3',1''-terphenyl]-4'-yl)-2,2,2-trifluoroethan-1-one, 1-([1,1',3',1''-terphenyl]-5'-yl)-2,2,2-trifluoroethan-1 -one, 1-([1,1',4',1''-terphenyl]-2'-yl)-2,2,2-trifluoroethan-1-one, 1-(2-chloro-3-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-chloro-4-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(2-chloro-6-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-chloro-2-nitrophenyl)-2,2,Examples include 2-trifluoroethan-1-one, 1-(3-chloro-4-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(3-chloro-5-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethan-1-one, 1-(4-chloro-2-nitrophenyl)-2,2,2-trifluoroethan-1-one, and 1-(4-chloro-3-nitrophenyl)-2,2,2-trifluoroethan-1-one.

[0016] Specific examples of the pentafluoroethyl ketones represented by the general formula (3) that can be produced by the present invention include 1-(naphthalen-1-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(naphthalen-2-yl)-2,2,3,3,3-pentafluoropropan-1-one, (E)-1,1,1,2,2-pentafluoro-5-phenylpent-4-en-3-one, 1-(1-methylindol-2-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(1-methylindol-3-yl)-2,2, 3,3,3-Pentafluoropropan-1-one, 1-(1-benzofuran-2-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(1-benzofuran-3-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(1-benzo[b]thiophen-2-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(1-benzo[b]thiophen-3-yl)-2,2,3,3,3-pentafluoropropan-1-one, 4-(4-chlorophenoxy)-1,1,1,2,2-pentafluoro 1-(2-fluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-fluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-fluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-chlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-chlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, Pentafluoropropan-1-one, 1-(4-chlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-iodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-iodophenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(4-iodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-methylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-methylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-methylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-ethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-ethylphenyl)-2, 2,3,3,3-Pentafluoropropan-1-one, 1-(4-ethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[n-propyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[n-propyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[n-propyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-isopropylphenyl)-2,2,3,3,3-pentafluoropropan 1-(3-isopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-isopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[n-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[n-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[n-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-isobutyl phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-isobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-isobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[sec-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[sec-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[sec-butyl]phenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(2-[tert-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[tert-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[tert-butyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-cyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-cyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one 1-(4-cyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-methoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-methoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-methoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-ethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-ethoxyphenyl)-2,2, 3,3,3-Pentafluoropropan-1-one, 1-(4-ethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-dimethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-dimethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-dimethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-diethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one 1-(3-diethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-diethylaminophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[benzyloxy]phenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(3-[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one 1-(4-[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[diethylaminosulfonyl]phenyl)-2,2,3, 3,3-Pentafluoropropan-1-one, 1-(2-[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-[diisopropyl 1-(3-[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1'-biphenyl]-2-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1'-biphenyl]-3-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1'-biphenyl]-4-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-difluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-difluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-difluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-difluorophenyl)- 1-(3,4-difluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-difluorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-dichlorophenyl)-2,2,3,3,3-pentafluoropropane -1-one, 1-(2,6-dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-dibromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dibromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-dibromophenyl)-2,2, 3,3,3-Pentafluoropropan-1-one, 1-(2,6-dibromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dibromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dibromophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-diiodophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one 1-(2,5-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dimethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-diethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-diethylphenyl)- 2,2,3,3,3-Pentafluoropropan-1-one, 1-(2,5-diethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-diethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-diethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-diethylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1- one, 1-(2,4-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-di-n-propylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-diisopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-diisopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-diisopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-diisopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-diisopropylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-diisopropylphenyl)- nyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-di-n-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-di-n-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-di-n-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-di-n-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-di-n-butylphenyl)-2,2,3,3, 3-Pentafluoropropan-1-one, 1-(3,5-di-n-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1- 1-(3,4-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-diisobutylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-di-sec-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-( 2,5-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-di-tert-butylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dicyclohexylphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2, 3-dimethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dimethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-dimethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-dimethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dimethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dimethoxyphenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(2,3-diethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-diethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-diethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-diethoxyphenyl) )-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-diethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-diethoxyphenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[dimethylamino]phenyl)-2,2,3,3,3-pentafluoro Propan-1-one, 1-(2,3-bis[diethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[diethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[diethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[diethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[diethylamino]phenyl)-2,2,3,3 ,3-pentafluoropropan-1-one, 1-(3,5-bis[diethylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis [di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[di-n-propylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[diisopropylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[diisopropylamino]phenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(2,5-bis[diisopropylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[diisopropylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[diisopropylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[diisopropylamino]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-dinitrophenyl) )-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-dinitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-dinitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-dinitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-dinitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-dinitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1 -(2,3-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1 -(3,5-di[benzyloxy]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[dimethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[diethylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[di-n-propylaminosulfonyl]phenyl)- 1-(2,4-bis[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,6-bis[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[di-n-propylaminosulfonyl]phenyl)- 1-(3,5-bis[di-n-propylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,3-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,4-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2,5-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-Pentafluoropropan-1-one, 1-(2,6-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,4-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3,5-bis[diisopropylaminosulfonyl]phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1',2',1''-terphenyl]-3'-yl)-2,2,3,3,3-pentafluoropropane -1-one, 1-([1,1',2',1''-terphenyl]-4'-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1',3',1''-terphenyl]-2'-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1',3',1''-terphenyl]-4'-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1',3',1''-terphenyl]-5'-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-([1,1',4' ,1''-terphenyl]-2'-yl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-chloro-3-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-chloro-4-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-chloro-5-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(2-chloro-6-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-chloro-2-nitro phenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-chloro-4-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(3-chloro-5-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(5-chloro-2-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-chloro-2-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, 1-(4-chloro-3-nitrophenyl)-2,2,3,3,3-pentafluoropropan-1-one, etc.

[0017] Potassium hexamethyldisilazide and / or potassium tert-butoxide can be used as the base applicable to the present invention, and the amount used is 1.0 to 5.0 moles per mole of the ester compounds used in the reaction.

[0018] The amount of trifluoromethane or pentafluoroethane applicable to the present invention can be 1.0 molar or more per mole of the ester compounds used in the reaction, but to complete the reaction, it is preferable to use 2.0 to 10.0 molar amounts. Excess trifluoromethane or pentafluoroethane may be recovered and reused.

[0019] As a solvent applicable to the present invention, a glyme-based solvent can be used. Examples of glyme-based solvents include diglyme, ethyl diglyme, butyl diglyme, methyl ethyl diglyme, triglyme, and tetraglyme. Among them, triglyme is preferred because it provides a good yield, and the amount used is preferably 5 to 200 times the weight of the ester compounds used in the reaction. Furthermore, if the solvent is inert to the reaction, it may be mixed with a glyme-based solvent. Examples of solvents that can be mixed 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.

[0020] The reaction temperature applicable to the present invention varies depending on the type of ester compound used in the reaction and the type of solvent used, but is usually preferably in the range of -50°C to 40°C, and particularly preferably -30°C to 40°C from the viewpoint of the cost of maintaining a low temperature during the reaction.

[0021] In the present invention, as described above, when an ester compound is mixed in the presence of an organic solvent by supplying a base and trifluoromethane or pentafluoroethane to a micromixer and a microreactor, or to a microreactor, the mixture can be mixed continuously, discontinuously, or sequentially.

[0022] When a micromixer and a microreactor are used, the ester compounds, base, and trifluoromethane or pentafluoroethane to be used in the reaction are first supplied to the micromixer and mixed, and then supplied to the microreactor and reacted. When using only a microreactor without a micromixer, the ester compounds, base, and trifluoromethane or pentafluoroethane used in the reaction are supplied to the microreactor and reacted. These reactants may be supplied all at once, or they may be added sequentially to the flow path of the microreactor. To ensure that the reactants are mixed within the microreactor after supply, the flow path may be designed or the reactant supply method may be implemented to change the laminar flow state to a turbulent flow.

[0023] The mixing time of the ester compounds used in the present invention with trifluoromethane or pentafluoroethane varies depending on the type and structure of the micromixer (micromixer) used, such as V-shaped, T-shaped, etc., but is usually in the range of 0.001 to 1.0 second. The reaction should be carried out at a supply rate that results in a mixing time of 1.0 second or less, taking into account the volume of the mixing section of the micromixer and the total volume of the feed per unit time.

[0024] The reaction time after mixing the ester compounds of the present invention, the base, and trifluoromethane or pentafluoroethane can be determined by the inner diameter and length of the microreactor (a device for carrying out chemical reactions in a microspace), and is usually within 10 seconds.

[0025] In the present invention, the micromixer and microreactor used in the reaction may be commonly available and commercially available ones, or may be ones designed suitably for the present invention. Furthermore, the micromixer and microreactor may be equipped with a heating or cooling device as needed, and other auxiliary equipment for promoting the reaction, etc. may also be added as appropriate.

[0026] The post-treatment after the reaction of the present invention is not particularly limited and can be carried out by a well-known method, for example, neutralization with an aqueous ammonium chloride solution, extraction with an organic solvent such as dichloromethane, drying with a desiccant such as anhydrous sodium sulfate, filtration, and concentration to obtain the target product as a crude product, which may then be purified by silica gel column chromatography or the like to obtain a purified target product. Furthermore, the hydrate may be converted into a ketone body by azeotropic dehydration using benzene, toluene, heptane, or the like. [Example]

[0027] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these examples.

[0028] The following instruments were used for the analysis: 1 H-NMR (300MHz), 19 F-NMR (282 MHz): Varian Mercury 300 and Bruker Avance 500. ESI-MS: Shimadzu LCMS-2020EV (SHIMADZU LCMS-2020EV). IR: JASCO FT / IR-4100. HRMS: Waters Synapt G2 HDMS (Waters Synapt G2 HDMS). Melting point: BUCHI Labortehnik AGM-565.

[0029] The reaction was carried out using a microflow reactor shown in FIG. In Figure 1, A is a mass flow controller (Fujikin FCST1005MLC). B-1 and B-2 are syringe pumps (manufactured by YMC) equipped with gas-tight syringes. C is a micromixer (Sugiyama Shoji 4-way swirl mixer 16YSM-0.8-0.5-S), made of SUS316 and with a volume of 60 μL. D denotes a microreactor, D-1 is made of SUS316, has an inner diameter of 0.8 mm, a length of 640 mm, and a volume of 0.32 mL, and D-2 is made of SUS316, has an inner diameter of 0.8 mm, a length of 1612 mm, and a volume of 0.81 mL. When using the microreactor indicated as D in Figure 1, D-1 and D-2 were interchanged as shown in the following examples.

[0030] Each part was connected with a 1 / 16 inch joint. The supply line for trifluoromethane or pentafluoroethane, indicated as "CF3H or CF3CF2H" in FIG. 1, was a pipe made of SUS316 and having an inner diameter of 0.8 mm. The supply lines for the potassium hexamethyldisilazide and potassium tert-butoxide solutions shown as "(KHMDS or t-BuOK) in solvent" in Figure 1 and the substituent R 1 ,R 2 The supply line for the solution of the ester compound having the formula (I) was a PTFE pipe with an inner diameter of 0.8 mm. The supply line for the KHMDS or t-BuOK solution and the supply line for the ester compound solution may be supplied separately or together. When potassium hexamethyldisilazide and potassium tert-butoxide are used as a mixture, the potassium hexamethyldisilazide and potassium tert-butoxide may be mixed in advance, or a new mixer and another syringe pump capable of mixing the two liquids may be added before the micromixer, and each liquid may be supplied separately.

[0031] Example 1 Preparation of 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a) [ka] A 0.60 M solution of methyl 4-methoxybenzoate (199 mg, 1.20 mmol) in triglyme (2.0 mL) was placed in a 5 mL gas-tight syringe and attached to a syringe pump (B-1). Similarly, a 0.60 M solution of potassium hexamethyldisilazide (359 mg, 1.80 mmol, 1.5 eq.) in triglyme (3 mL) was placed in another gas-tight syringe and attached to a syringe pump (B-2). The methyl 4-methoxybenzoate solution was set to flow at 0.33 mL / min and the potassium hexamethyldisilazide solution at 0.50 mL / min. These were fed into mixer C and microreactor D (using D-2) at room temperature, while trifluoromethane (0.1 MPa) was fed at 25 mL / min (trifluoromethane / methyl 4-methoxybenzoate = 5.20 / 1 mol / mol). Once the trifluoromethane supply stabilized, the distillate from the outlet of microreactor (D) was quenched with saturated aqueous ammonium chloride solution for 2 minutes. The resulting organic layer was then extracted with dichloromethane, washed with saturated brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the target compound, 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a). During the stable reaction, the mixing time in the micromixer was 0.14 seconds, and the reaction time in the microreactor was 1.9 seconds. The obtained crude product was analyzed by benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a), was 64%. The obtained crude product was purified by silica gel column chromatography (n-hexane / ethyl acetate=95 / 5 vol / vol) to obtain the target product as a colorless transparent liquid (152 mg, 0.74 mmol, yield 62%).

[0032] The analysis results were as follows: 1 H-NMR (300MHz, CDCl3) δ: 8.06 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.5(s,3F)ppm. GC-MS(EI, m / z): 135[M-CF3] + .

[0033] Examples 2-4 Preparation of 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a) Using the same reaction apparatus as in Example 1, but replacing the microreactor with D-1, a methyl 4-methoxybenzoate solution (0.60 M) was supplied at 0.33 mL / min, a base solution (0.60 M) using the base shown in Table 1 was supplied at 0.50 mL / min, and trifluoromethane (0.1 MPa) was supplied at 25.0 mL / min, and the reaction was carried out at the temperature shown in Table 1. The obtained crude product was analyzed using benzotrifluoride as an internal standard substance. 19 F-NMR measurement was carried out, and the yield of the target product, 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a), was calculated and the results are shown in Table 1. During stable reaction, the mixing time in the micromixer was 0.14 seconds, and the reaction time in the microreactor was 0.74 seconds.

[0034] [Table 1]

[0035] Comparative Example 1 Preparation of 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a) A test tube equipped with a stir bar was charged with methyl 4-methoxybenzoate (66.5 mg, 0.4 mmol) and triglyme (0.7 mL). Trifluoromethane (9.9 mL, 1.1 eq.) was added via syringe while the container was cooled with liquid nitrogen. A solution of potassium hexamethyldisilazide (160 mg, 0.8 mmol, 2.0 eq.) in triglyme (0.3 mL) was then added to the test tube, which had been cooled to -40 °C, and the reaction was carried out at the same temperature for 4 hours. After completion of the reaction, 1 M hydrochloric acid (1.0 mL) was added, and the aqueous layer was extracted with dichloromethane (1.0 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The obtained crude product was purified by silica gel column chromatography (n-hexane / diethyl ether=9 / 1 vol / vol) to obtain the target 2,2,2-trifluoro-1-(4-methoxyphenyl)ethan-1-one (a) (36.9 mg, 0.181 mmol, yield 45%).

[0036] From the above Examples 1 to 4 and Comparative Example 1, the following can be seen. Comparing Example 1 and Example 2, Example 1 used a microreactor D-2 (volume 0.81 mL) and a reaction time of 1.9 seconds, while Example 2 used a microreactor D-1 (volume 0.32 mL) and a reaction time of 0.74 seconds. This difference in conditions is thought to be the reason for the difference in yield between Example 1 (64%) and Example 2 (47%). Therefore, although it is necessary to consider the conditions for setting the reaction rate, it is clear that the yield can be controlled by selecting the length and inner diameter of the microreactor.

[0037] Comparing Example 2 and Example 3, the reaction temperature in Example 2 was room temperature, while in Example 3 it was -30°C. This difference in reaction temperature is thought to be the reason for the difference in yield, 47% in Example 2 and 15% in Example 3. Therefore, in a reaction system having a predetermined length and an extremely narrow inner diameter, such as a microreactor, it is possible to precisely control the temperature by installing a temperature control means outside the reactor, and as a result, it is possible to precisely control the reaction rate.

[0038] Comparing Example 3 and Example 4, Example 3 uses a potassium hexamethyldisilazide solution as the base at −30° C., while Example 4 uses a potassium tert-butoxide solution as the base at −10° C. Despite these differences in reaction conditions, there is no significant difference between the two, with the yield being 15% in Example 3 and 17% in Example 4, and either base is applicable.

[0039] Comparing Example 1 and Comparative Example 1, Example 1 used D-2 (volume 0.81 mL) as a microreactor, while Comparative Example 1 did not use a microreactor and performed a batch reaction. This is thought to be the reason for the difference in yield between Example 1 (64%) and Comparative Example 1 (45%). Here, the reaction time in Example 1 is 1.9 seconds, while the reaction time in Comparative Example 1 is 4 hours. Of course, in Example 1, the reaction time can be calculated based on the reactant volume depending on the flow rate in order to react the entire amount at the time of charging, but at least from the viewpoint of reaction time alone, it is possible to achieve an efficient reaction in a short time compared to Comparative Example 1. This reaction time can be achieved by selecting the length, inner diameter, and flow rate of the reactants of the microreactor, and it appears that even with an extremely small reaction system, it is possible to obtain the same target product as with a reaction system comparable to that of a large plant.

[0040] Examples 5 to 24 Preparation of various trifluoromethyl ketones The same reaction apparatus as in Example 1 was used, microreactor D-2 was used, and the same reaction procedures as in Example 1 were carried out except that the ester compounds shown in Table 1 were used instead of methyl 4-methoxybenzoate, to obtain the target trifluoromethyl ketones. The results are shown in Table 2, and the results of various analyses are described below. During stable reactions, the mixing time in the micromixer was 0.14 seconds, and the reaction time in the microreactor was 1.9 seconds.

[0041] [Table 2] TIFF0007766452000008.tif197142TIFF0007766452000009.tif23145

[0042] 1) 1-(4-[tert-butyl]phenyl)-2,2,2-trifluoroethan-1-one (b) The obtained crude product was purified with n-hexane / dichloromethane=9 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3) δ:8.02(d,J=7.9Hz,2H),7.79-7.54(m,2H),1.36(s,9H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.8(s,3F)ppm. GC-MS(EI, m / z): 230[M] + ,161[M-CF3] + . 2) 1-(4-cyclohexylphenyl)-2,2,2-trifluoroethan-1-one (c) 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=7.6Hz,2H),7.38(d,J=8.8Hz,2H),2.64-2.57(m,1H),1.89-1.77(m,5H),1.51-1.21(m,5H). 19 F-NMR (282MHz, CDCl3)δ: -71.8(s,3F)ppm. GC-MS(EI, m / z): 187[M-CF3] + . 3) 1-([1,1'-biphenyl]-4-yl)-2,2,2-trifluoroethan-1-one (d) The obtained crude product was purified with n-hexane / dichloromethane=95 / 5 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3)δ:8.16(d,J=8.2Hz,2H),7.78(d,J=8.8Hz,2H),7.66(dd,J=8.2,1.5Hz,2H),7.53-7.45(m,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.8(s,3F)ppm. GC-MS(EI, m / z): 181[M-CF3] + . 4) 1-(3-[dimethylamino]phenyl)-2,2,2-trifluoroethan-1-one (e) The obtained crude product was purified with n-hexane / dichloromethane=8 / 2 (vol / vol). yellow liquid. 1 H-NMR (300MHz, CDCl3) δ:7.38-7.35(m,3H),7.06-7.02(m,1H),3.02(s,6H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.4(s,3F)ppm. GC-MS(EI, m / z): 217[M] + ,148[M-CF3] + ,120[M-COCF3] + . 5) 1-(2-iodophenyl)-2,2,2-trifluoroethan-1-one (f) The obtained crude product was purified with n-hexane / dichloromethane=98 / 2 (vol / vol). Pale yellow liquid. 1 H-NMR (300MHz, CDCl3) δ:8.10(dd,J=7.9,1.2Hz,1H),7.77-7.72(m,1H),7.54-7.49(m,1H),7.32-7.29(m,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.8(s,3F)ppm. GC-MS (EI, m / z): 300 [M] +,231[M-CF3] + ,203[M-COCF3] + . 6) 1-([1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethan-1-one (g) The obtained crude product was purified with n-hexane. Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:7.74(d,J=7.9Hz,1H),7.69-7.63(m,1H),7.53-7.36(m,5H),7.28-7.25(m,2H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -70.9(s,3F)ppm. GC-MS (EI, m / z): 250 [M] + ,181[M-CF3] + . 7) 1-(3,4-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one(h) The obtained crude product was purified with n-hexane / ethyl acetate=9 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3)δ:7.77-7.71(m,1H),7.58(d,J=1.8Hz,1H),6.96(d,J=8.5Hz,1H),4.00(s,3H),3.96(s,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -70.9(s,3F)ppm. GC-MS(EI, m / z): 165[M-CF3] + . 8) 1-(3,5-dimethoxyphenyl)-2,2,2-trifluoroethan-1-one(i) The obtained crude product was purified with n-hexane / ethyl acetate=9 / 1 (vol / vol). Pale yellow liquid. 1H-NMR (300MHz, CDCl3) δ:7.20-7.19(m,2H),6.79-6.77(m,1H),3.86(s,6H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.6(s,3F)ppm. GC-MS(EI, m / z): 234[M] + ,165[M-CF3] + ,137[M-COCF3] + . 9) 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethan-1-one(j) The obtained crude product was purified with n-hexane / dichloromethane=8 / 2 (vol / vol). yellow liquid. 1 H-NMR (300MHz, CDCl3) δ:8.27(d,J=9.1Hz,1H),7.76(dd,J=8.9,2.2Hz,1H),7.50(d,J=2.3Hz,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -76.2(s,3F)ppm. GC-MS(EI, m / z): 184[M-CF3] + . 10) 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethan-1-one(k) The obtained crude product was purified with n-hexane / dichloromethane=8 / 2 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 7.66 (s, 1H), 7.55-7.47 (m, 2H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -73.9(s,3F)ppm. GC-MS(EI, m / z): 242[M] + ,173[M-CF3] + ,145[M-COCF3] + . 11)1-(3,5-dichlorophenyl)-2,2,2-trifluoroethan-1-one(l) The obtained crude product was dissolved in benzene (3 mL) and subjected to azeotropic dehydration using a Dean-Stark dehydrator for 12 hours, and then purified by silica gel column chromatography (n-hexane / dichloromethane = 8 / 2 (vol / vol)). Brown liquid. 1 H-NMR (300MHz, CDCl3) δ:7.93-7.92(m,2H),7.71-7.70(m,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.1(s,3F)ppm. 13 C-NMR (126MHz, CDCl3)δ:179.1-178.6(m),142.96,136.49,135.44,132.28,129.26,128.41,116.30 (q,J=290.7Hz),29.84,2.64ppm. ATR-FTIR(neat):ν=2927,2854,1731,1568,1524,1423,1366,1254,1188,1150,1065,1001,852,812,764,709,525cm- 1 . HRMS (EI, m / z): C8H3OF3Cl2 ([M] + ) Calculated value: 241.9513, measured value: 241.9516. 12) 1-(Naphthalen-2-yl)-2,2,2-trifluoroethan-1-one(m) The obtained crude product was purified with n-hexane / diethyl ether=9 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ: 8.63 (s, 1H), 8.10-7.91 (m, 4H), 7.73-7.60 (m, 2H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.2(s,3F)ppm. GC-MS(EI, m / z): 224[M]+ ,155[M-CF3] + ,127[M-COCF3] + . 13) 1-(naphthalen-1-yl)-2,2,2-trifluoroethan-1-one(n) The obtained crude product was purified with n-hexane. Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:8.85(d,J=8.5Hz,1H),8.23-8.16(m,2H),7.95(d,J=8.2Hz,1H),7.74-7.57(m,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -70.6(s,3F)ppm. GC-MS(EI, m / z): 224[M] + ,155[M-CF3] + ,127[M-COCF3] + . 14) (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one(o) The obtained crude product was purified with n-hexane / dichloromethane=95 / 5 (vol / vol). yellow liquid. 1 H-NMR (300MHz, CDCl3)δ:7.98(d,J=16.1Hz,1H),7.69-7.61(m,2H),7.53-7.42(m,3H),7.02(d,J=15.8 Hz,1H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -78.1(s,3F)ppm. GC-MS (EI, m / z): 200 [M] + ,131[M-CF3] + ,103[M-COCF3] + . 15) 1-(1-methylindol-2-yl)-2,2,2-trifluoroethan-1-one(p) The obtained crude product was purified with n-hexane / dichloromethane=9 / 1 (vol / vol). Yellow solid. 1 H-NMR (300MHz, CDCl3) δ:7.76(d,J=8.2Hz,1H),7.59(d,J=1.8Hz,1H),7.52-7.41(m,2H),7.24-7.18(m,1H),4.12(s,3H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -71.4(s,3F)ppm. GC-MS(EI, m / z): 227[M] + ,158[M-CF3] + . 16) 1-(benzofuran-2-yl)-2,2,2-trifluoroethan-1-one (q) The obtained crude product was purified with n-hexane / dichloromethane=9 / 1 (vol / vol). White solid. 1 H-NMR (300MHz, CDCl3) δ: 7.87-7.86 (m, 1H), 7.82-7.79 (m, 1H), 7.68-7.58 (m, 2H), 7.43-7.38 (m, 1H) ppm. 19 F-NMR (282MHz, CDCl3)δ: -73.6(s,3F)ppm. GC-MS(EI, m / z): 214[M] + ,145[M-CF3] + . 17) 1-(benzo[b]thiophen-2-yl)-2,2,2-trifluoroethan-1-one (r) The obtained crude product was purified with n-hexane / dichloromethane=9 / 1 (vol / vol). Yellow solid. 1 H-NMR (300MHz, CDCl3) δ: 8.24 (s, 1H), 7.96 (dd, J=19.2, 8.1Hz, 2H), 7.60-7.46 (m, 2H) ppm. 19F-NMR (282MHz, CDCl3)δ: -72.3(s,3F)ppm. GC-MS(EI, m / z): 230[M] + ,161[M-CF3] + ,133[M-COCF3] + . 18) 1-(2-[benzyloxy]phenyl)-2,2,2-trifluoroethan-1-one(s) The obtained crude product was purified with n-hexane / ethyl acetate=9 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3) δ:7.71-7.68(m,1H),7.59-7.53(m,1H),7.46-7.34(m,5H),7.02-7.11(2H),5.20(s,2H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -74.2(s,3F)ppm. GC-MS(EI, m / z): 280[M] + ,211[M-CF3] + . 19) N,N-dipropyl-4-(2,2,2-trifluoroacetyl)benzenesulfonamide (t) The obtained crude product was dissolved in benzene (3 mL) and subjected to azeotropic dehydration using a Dean-Stark dehydrator for 12 hours, and then purified by silica gel column chromatography (n-hexane / diethyl ether = 1 / 1 (vol / vol)). White solid. 1 H-NMR(300MHz, CDCl3)δ:8.20(d,J=7.9Hz,2H),8.00-7.97(m,2H),3.15-3.10(m,4H),1.63-1.51(m,4H),0.88(t,J=7.3Hz,6H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.2(s,3F)ppm. GC-MS(EI, m / z): 237[M-NPr2] +,173[M-SO2NPr2] + . 20) 3-(4-chlorophenoxy)-1,1,1-trifluoro-3-methylbutan-2-one(u) The obtained crude product was dissolved in benzene (3 mL) and subjected to azeotropic dehydration using a Dean-Stark dehydrator for 12 hours, and then purified by silica gel column chromatography (n-hexane / ethyl acetate = 8 / 2 (vol / vol)). Light brown liquid. 1 H-NMR (300MHz, CDCl3) δ:7.29-7.23(m,2H),6.87-6.82(m,2H),1.58(s,6H)ppm. 19 F-NMR (282MHz, CDCl3)δ: -72.5(s,3F)ppm. 13 C-NMR (126MHz, CDCl3) δ: 192.4 (q, J = 32.6 Hz), 152.5, 151.5, 129.6, 129.4, 126.1, 123.1, 116.2 (q, J = 293.7 Hz), 83.5, 24.2, 22.1 ppm. ATR-FTIR(neat):ν=2996,1765,1592,1489,1386,1305,1216,1093,1012,867,843,741,664,515cm- 1 . HRMS(EI,m / z):C 11 H 10 O2F3Cl([M] + ) Calculated value: 266.0321, measured value: 266.0331.

[0043] Example 25 Preparation of 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-one (v) [ka] The same reaction apparatus as in Example 1 was used, but the microreactor D-2 was replaced with D-1. A methyl 4-methoxybenzoate solution (0.60 M) was supplied at 0.33 mL / min, a potassium hexamethyldisilazide solution (0.60 M) was supplied at 0.50 mL / min, and trifluoromethane was replaced with pentafluoroethane (0.1 MPa) at 25.0 mL / min. The reaction temperature was changed from room temperature to -30°C, and the reaction was carried out. The obtained crude product was analyzed using benzotrifluoride as an internal standard. 19 F-NMR analysis revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-one (v), was 80%. During the stable reaction, the mixing time in the micromixer was 0.14 seconds, and the reaction time in the microreactor was 0.74 seconds.

[0044] The analysis results were as follows: 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.

[0045] Examples 26-27 Preparation of 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-one (v) The same reaction apparatus as in Example 1 was used, except that the microreactor D-2 was replaced with D-1, a 4-methoxybenzoate methyl solution (0.60 M) was fed at 0.33 mL / min, a potassium hexamethyldisilazide solution (0.60 M) was fed at 0.50 mL / min, and trifluoromethane was replaced with pentafluoroethane (0.1 MPa) fed at 25.0 mL / min. The reaction was carried out at the temperatures shown in Table 3. The same reaction procedures as in Example 1 were carried out to obtain the target 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-one (v). The results are shown in Table 3. During stable reaction, the mixing time in the micromixer was 0.14 seconds, and the reaction time in the microreactor was 0.74 seconds.

[0046] [Table 3]

[0047] Comparative Example 2 Preparation of 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-one (v) A test tube equipped with a stir bar was charged with methyl 4-methoxybenzoate (33.2 mg, 0.2 mmol) and triglyme (0.7 mL). Pentafluoroethane (9.9 mL, 1.1 eq.) was added via syringe while the vessel was cooled with liquid nitrogen. A solution of potassium hexamethyldisilazide (160 mg, 0.8 mmol, 2.0 eq.) in triglyme (0.3 mL) was then added to the test tube, which had been cooled to -40 °C, and the reaction was carried out at the same temperature for 4 hours. After completion of the reaction, 1 M hydrochloric acid (1.0 mL) was added, and the aqueous layer was extracted with dichloromethane (1.0 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the 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-(4-methoxyphenyl)propan-1-one (v) (35.6 mg, 0.140 mmol, 70% yield). [Industrial Applicability]

[0048] The trifluoromethyl ketones and pentafluoroethyl ketones obtained by the method of the present invention are useful compounds as intermediates in the production of pharmaceuticals, agricultural chemicals, electronic materials, and the like. [Explanation of symbols]

[0049] A: Mass flow controller B-1, B-2: Syringe pump C: Micromixer D: Microreactor

Claims

1. The following general formula (1) 【Transformation 7】 [In formula (1), R １ is 1-methylindol-2-yl, 1-benzofuran-2-yl, 1-benzo[b]thiophen-2-yl, 2-(4-chlorophenoxy)propan-2-yl, or the following general formula (2): 【Transformation 8】 (In formula (2), R ３ and R ４ each independently represents a dimethylamino group, a diethylamino group, a nitro group, a benzyloxy group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, or a dipropylaminosulfonyl group, and R ２ indicates a methyl group] and reacting an ester compound represented by the following general formula (3): 【Chemistry 9】 [In formula (3), Rf represents a trifluoromethyl group, and R １ is 1-methylindol-2-yl, 1-benzofuran-2-yl, 1-benzo[b]thiophen-2-yl, 2-(4-chlorophenoxy)propan-2-yl, or the following general formula (2): 【Chemistry 10】 (In formula (2), R ３ and R ４ each independently represents a dimethylamino group, a diethylamino group, a nitro group, a benzyloxy group, a dimethylaminosulfonyl group, a diethylaminosulfonyl group, or a dipropylaminosulfonyl group. A method for producing a trifluoromethyl ketone represented by the formula:

2. A method for producing trifluoromethyl ketone as described in claim 1, characterized in that the glyme-based solvent is triglyme.

3. The method for producing trifluoromethyl ketone according to claim 1 or 2, wherein the trifluoromethyl group substitution reaction of the ester compound represented by formula (1) is carried out at −30° C. to 40° C.

4. The method for producing trifluoromethyl ketone according to any one of claims 1 to 3, wherein the base is potassium hexamethyldisilazide and / or potassium tert-butoxide, and is used in an amount of 1.0 molar equivalent to 5.0 molar equivalents relative to the ester compound represented by formula (1).

5. The method for producing trifluoromethyl ketone according to any one of claims 1 to 4, characterized in that the mixing time of the ester compound, the base, and the trifluoromethane in the micromixer is in the range of 0.001 seconds to 1 second.

6. The method for producing trifluoromethyl ketone according to any one of claims 1 to 5, characterized in that a micromixer having a structure capable of simultaneously mixing three components is used.

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