Method for producing a compound containing a pentafluoroethyl group

Abstract

To provide a production method that uses pentafluoroethane as raw material, creates a pentafluoroethyl anion in general-purpose solvent, reacting it with a carbonyl compound, to give a trifluoroethyl group-containing compound, wherein the production method has practical utility, or can be performed economically, safely and industrially.SOLUTION: The present invention discloses a method for preparing a pentafluoroethyl group-containing compound by mixing and reacting a carbonyl compound, in the presence of an organic solvent, with a base and pentafluoroethane fed thereto, using a micro mixer and a micro reactor.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a pentafluoroethyl group-containing compound by reacting a carbonyl compound with a pentafluoroethyl anion generated from pentafluoroethane. The pentafluoroethyl group-containing compound obtained by the production method of the present invention is a useful compound as an intermediate in the production of pharmaceuticals and agricultural chemicals or an intermediate in the production of electronic materials. [Background technology]

[0002] It has been known that the pentafluoroethyl anion is unstable and decomposes at temperatures of -50°C or higher. For this reason, a method of using it in the form of (pentafluoroethyl)trimethylsilane in the reaction is known (see, for example, Non-Patent Document 1, etc.). Also known are a method in which a mixture of pentafluoroethyl iodide and carbonyl compounds is reacted with methyllithium at 0°C using a microflow reactor, and a method in which trifluoroethyl anions are generated by reacting pentafluoroethyl iodide with methyllithium at -50°C or lower, and then the anions are immediately reacted with carbonyl compounds (e.g., see Non-Patent Document 2, etc.).

[0003] The method described in Non-Patent Document 1 allows the reaction to take place under mild conditions, but has the problem that (pentafluoroethyl)trimethylsilane is expensive. The method described in Non-Patent Document 2 has the problem that it requires the use of unstable methyllithium, and also has the problem that lithium iodide produced as a by-product of the reaction of pentafluoroethyl iodide and methyllithium precipitates in the microflow reactor, causing blockage. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Uneyama, K. et al., J. Fluor. Chem. 2008, 129, 550. [Non-Patent Document 2] Jun-ich Yoshida et al., Org. & Biomol. Chem. 2011, 9, 7559. Summary of the Invention [Problem to be solved by the invention]

[0005] The object of the present invention is to provide a practical production method, i.e., an economical, safe and industrial production method, in which pentafluoroethane is used as a raw material, pentafluoroethyl anions are generated in a general-purpose solvent, and the anions are reacted with a carbonyl compound to obtain a trifluoroethyl group-containing compound. [Means for solving the problem]

[0006] The present inventors have conducted extensive research into a method for obtaining carbonyl compounds using pentafluoroethane as a raw material, and as a result have found that the target trifluoroethyl group-containing compound can be obtained by instantaneously mixing pentafluoroethane, a base, and a carbonyl compound in a short period of time of 1.0 second or less using a micromixer and a microreactor in a temperature range of -50°C to 40°C, thereby completing the present invention.

[0007] That is, the present invention relates to the inventions described below. [1] The following general formula (1) [ka] [In formula (1), R 1 represents a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a furan-3-yl group, a thiophene-2-yl group, a thiophene-3-yl group, a pyridin-2-yl group, a pyridin-3-yl group, a pyridin-4-yl group, or a group represented by the following general formula (2): [ka] (In formula (2), R3 represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R 2 represents a hydrogen atom, a pyridin-2-yl group, or a group represented by the following general formula (3): [ka] (In formula (3), R 4 represents a hydrogen atom or a methoxy group), or the following general formula (4): [ka] (In formula (4), R 5 represents a hydrogen atom or a methoxy group, and R 1 and R 2 may be bonded to form a ring. The carbonyl compound represented by the following general formula (5) is reacted with a base and pentafluoroethane in the presence of an organic solvent using a micromixer and a microreactor: [ka] [In formula (5), R 1 is a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophene-2-yl group, a pyridin-2-yl group, or a group represented by the following general formula (6): [ka] (In formula (6), R 3 represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R 2 represents a hydrogen atom, a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophene-2-yl group, a pyridin-2-yl group, or a group represented by the following general formula (7): [ka] (In formula (7), R 4represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group), or a group represented by the following general formula (8): [ka] (In formula (8), R 5 represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R 1 and R 2 may be bonded to form a ring. A method for producing a pentafluoroethyl group-containing compound represented by the following formula: When the carbonyl compound is supplied to the micromixer and the microreactor together with the base and pentafluoroethane in the presence of an organic solvent and mixed therewith, the supply may be continuous or may be interrupted. [2] The method for producing a pentafluoroethyl group-containing compound according to item [1], characterized in that the base is potassium tert-butoxide and / or potassium hexamethyldisilazide. [3] The method for producing a pentafluoroethyl group-containing compound according to item [1] or [2], characterized in that the organic solvent is toluene, tetrahydrofuran, and / or N,N-dimethylformamide. [4] The method for producing a pentafluoroethyl group-containing compound according to any one of [1] to [3], wherein the reaction temperature is in the range of -50°C to 40°C. [5] The method for producing a pentafluoroethyl group-containing compound according to any one of items [1] to [4], wherein the mixing time of the carbonyl compound, the base, and the pentafluoroethane in the micromixer is in the range of 0.001 seconds to 1 second. [6] The present invention provides a method for producing a pentafluoroethyl group-containing compound according to any one of [1] to [5], characterized in that a micromixer having a structure capable of simultaneously mixing three components is used. Effect of the Invention

[0008] According to the present invention, it has become possible to use pentafluoroethane as a raw material, generate chemically unstable pentafluoroethyl anions, and carry out pentafluoroethylation to various carbonyl compounds under mild conditions. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram showing an example of a microflow reactor in which the present invention is implemented. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention will be described in detail below. The apparatus applicable to the present invention is a continuous reaction apparatus that is composed of a metering pump that supplies a predetermined amount of a solution of carbonyl compounds and a solution of a base, a mass flow controller that supplies a predetermined amount of trifluoroethane as a gas, a micromixer that mixes the solution of carbonyl compounds, the solution of a base, and trifluoroethane, and a microreactor that reacts the mixture, and that continuously supplies a predetermined amount of each reagent to carry out the reaction. When carrying out the reaction, a three-component mixing type micromixer may be used, or a two-component mixing type micromixer may be used in which a base and carbonyl compounds are mixed in advance and reacted with trifluoroethane.

[0011] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is a hydrogen atom include 1-naphthaldehyde, 2-naphthaldehyde, furan-2-carboxaldehyde, furan-3-carboxaldehyde, 2-thiophenecarboxaldehyde, 3-thiophenecarboxaldehyde, 2-pyridinecarboxaldehyde, 3-pyridinecarboxaldehyde, 4-pyridinecarboxaldehyde, benzaldehyde, 2-methylbenzaldehyde, 3-methylbenzaldehyde, 4-methylbenzaldehyde, 2-fluorobenzaldehyde, 3-fluorobenzaldehyde, 4-fluorobenzaldehyde, 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromo Benzaldehyde, 2-iodobenzaldehyde, 3-iodobenzaldehyde, 4-iodobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 2-(trifluoromethyl)benzaldehyde, 3-(trifluoromethyl)benzaldehyde, 4-(trifluoromethyl)benzaldehyde, 2-methoxybenzaldehyde, 3-methoxybenzaldehyde, 4-methoxybenzaldehyde, 2-(trifluoromethoxy)benzaldehyde, 3-(trifluoromethoxy)benzaldehyde, 4-(trifluoromethoxy)benzaldehyde, biphenyl-2-carboxaldehyde, biphenyl-3-carboxaldehyde, biphenyl-4-carboxaldehyde, and the like.

[0012] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is a phenyl group include 1-benzoylnaphthalene, 2-benzoylnaphthalene, 2-benzoylfuran, 3-benzoylfuran, 2-benzoylthiophene, 3-benzoylthiophene, 2-benzoylpyridine, 3-benzoylpyridine, 4-benzoylpyridine, benzophenone, 2-methylbenzophenone, 3-methylbenzophenone, 4-methylbenzophenone, 2-fluorobenzophenone, 3-fluorobenzophenone, 4-fluorobenzophenone, 2-chlorobenzophenone, 3-chlorobenzophenone, 4-chlorobenzophenone, 2-bromobenzophenone, 3-bromobenzophenone, 4-bromobenzophenone, 2-iodobenzophenone, Non, 3-iodobenzophenone, 4-iodobenzophenone, 2-nitrobenzophenone, 3-nitrobenzophenone, 4-nitrobenzophenone, 2-(trifluoromethyl)benzophenone, 3-(trifluoromethyl)benzophenone, 4-(trifluoromethyl)benzophenone, 2-methoxybenzophenone, 3-methoxybenzophenone, 4-methoxybenzophenone, 2-(trifluoromethoxy)benzophenone, 2-(trifluoromethoxy)benzophenone, 3-(trifluoromethoxy)benzophenone, 4-(trifluoromethoxy)benzophenone, 2-biphenyl phenyl ketone, 3-biphenyl phenyl ketone, 4-biphenyl phenyl ketone, and the like.

[0013] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is a 2-methoxyphenyl group include 1-(2-methoxybenzoyl)naphthalene, 2-(2-methoxybenzoyl)naphthalene, 2-(2-methoxybenzoyl)furan, 3-(2-methoxybenzoyl)furan, 2-(2-methoxybenzoyl)thiophene, 3-(2-methoxybenzoyl)thiophene, 2-(2-methoxybenzoyl)pyridine, 3-(2-methoxybenzoyl)pyridine, 4-(2-methoxybenzoyl)pyridine, 2-methyl-2'-methoxybenzophenone, benzophenone, 3-methyl-2´-methoxybenzophenone, 4-methyl-2´-methoxybenzophenone, 2-fluoro-2´-methoxybenzophenone, 3-fluoro-2´-methoxybenzophenone, 4-fluoro-2´-methoxybenzophenone, 2-chloro-2´-methoxybenzophenone, 3-chloro-2´-methoxybenzophenone, 4-chloro-2´-methoxybenzophenone, 2-bromo-2´-methoxybenzophenone, 3-bromo-2´-methoxybenzophenone, 4-bromo-2´-methoxybenzophenone Non, 2-iodo-2´-methoxybenzophenone, 3-iodo-2´-methoxybenzophenone, 4-iodo-2´-methoxybenzophenone, 2-nitro-2´-methoxybenzophenone, 3-nitro-2´-methoxybenzophenone, 4-nitro-2´-methoxybenzophenone, 2-(trifluoromethyl)-2´-methoxybenzophenone, 3-(trifluoromethyl)-2´-methoxybenzophenone, 4-(trifluoromethyl)-2´-methoxybenzophenone, 2,2´-dimethoxybenzophenone , 2,3'-dimethoxybenzophenone, 2,4'-dimethoxybenzophenone, 2-(trifluoromethoxy)-2'-methoxybenzophenone, 2-(trifluoromethoxy)-2'-methoxybenzophenone, 3-(trifluoromethoxy)-2'-methoxybenzophenone, 4-(trifluoromethoxy)-2'-methoxybenzophenone, 2-biphenyl(2-methoxyphenyl)ketone, 3-biphenyl(2-methoxyphenyl)ketone, 4-biphenyl(2-methoxyphenyl)ketone, and the like.

[0014] Represented by general formula (1) applicable to the present invention, R2 Specific examples of the compound in which is a 3-methoxyphenyl group include 1-(3-methoxybenzoyl)naphthalene, 2-(3-methoxybenzoyl)naphthalene, 2-(3-methoxybenzoyl)furan, 3-(3-methoxybenzoyl)furan, 2-(3-methoxybenzoyl)thiophene, 3-(3-methoxybenzoyl)thiophene, 2-(3-methoxybenzoyl)pyridine, 3-(3-methoxybenzoyl)pyridine, 4-(3-methoxybenzoyl)pyridine, 2-methyl-3'-methoxybenzyl, and 2-methyl-3'-methoxybenzyl. benzophenone, 3-methyl-3´-methoxybenzophenone, 4-methyl-3´-methoxybenzophenone, 2-fluoro-3´-methoxybenzophenone, 3-fluoro-3´-methoxybenzophenone, 4-fluoro-3´-methoxybenzophenone, 2-chloro-3´-methoxybenzophenone, 3-chloro-3´-methoxybenzophenone, 4-chloro-3´-methoxybenzophenone, 2-bromo-3´-methoxybenzophenone, 3-bromo-3´-methoxybenzophenone, 4-bromo-3´- Methoxybenzophenone, 2-iodo-3´-methoxybenzophenone, 3-iodo-3´-methoxybenzophenone, 4-iodo-3´-methoxybenzophenone, 2-nitro-3´-methoxybenzophenone, 3-nitro-3´-methoxybenzophenone, 4-nitro-3´-methoxybenzophenone, 2-(trifluoromethyl)-3´-methoxybenzophenone, 3-(trifluoromethyl)-3´-methoxybenzophenone, 4-(trifluoromethyl)-3´-methoxybenzophenone, 3,3 Examples of such benzophenones include 1'-dimethoxybenzophenone, 3,4'-dimethoxybenzophenone, 2-(trifluoromethoxy)-3'-methoxybenzophenone, 2-(trifluoromethoxy)-3'-methoxybenzophenone, 3-(trifluoromethoxy)-3'-methoxybenzophenone, 4-(trifluoromethoxy)-3'-methoxybenzophenone, 2-biphenyl(3-methoxyphenyl)ketone, 3-biphenyl(3-methoxyphenyl)ketone, and 4-biphenyl(3-methoxyphenyl)ketone.

[0015] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is a 4-methoxyphenyl group include 1-(4-methoxybenzoyl)naphthalene, 2-(4-methoxybenzoyl)naphthalene, 2-(4-methoxybenzoyl)furan, 3-(4-methoxybenzoyl)furan, 2-(4-methoxybenzoyl)thiophene, 3-(4-methoxybenzoyl)thiophene, 2-(4-methoxybenzoyl)pyridine, 3-(4-methoxybenzoyl)pyridine, 4-(4-methoxybenzoyl)pyridine, 2-methyl-4'-methylbenzoyl Toxicbenzophenone, 3-methyl-4´-methoxybenzophenone, 4-methyl-4´-methoxybenzophenone, 2-fluoro-4´-methoxybenzophenone, 3-fluoro-4´-methoxybenzophenone, 4-fluoro-4´-methoxybenzophenone, 2-chloro-4´-methoxybenzophenone, 3-chloro-4´-methoxybenzophenone, 4-chloro-4´-methoxybenzophenone, 2-bromo-4´-methoxybenzophenone, 3-bromo-4´-methoxybenzophenone, 4-Bromo-4´-methoxybenzophenone, 2-iodo-4´-methoxybenzophenone, 3-iodo-4´-methoxybenzophenone, 4-iodo-4´-methoxybenzophenone, 2-nitro-4´-methoxybenzophenone, 3-nitro-4´-methoxybenzophenone, 4-nitro-4´-methoxybenzophenone, 2-(trifluoromethyl)-4´-methoxybenzophenone, 3-(trifluoromethyl)-4´-methoxybenzophenone, 4-(trifluoromethyl)-4´-meth Examples of such benzophenone include 4,4'-dimethoxybenzophenone, 2-(trifluoromethoxy)-4'-methoxybenzophenone, 2-(trifluoromethoxy)-4'-methoxybenzophenone, 3-(trifluoromethoxy)-4'-methoxybenzophenone, 4-(trifluoromethoxy)-4'-methoxybenzophenone, 2-biphenyl(4-methoxyphenyl)ketone, 3-biphenyl(4-methoxyphenyl)ketone, and 4-biphenyl(4-methoxyphenyl)ketone.

[0016] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is a pyridin-2-yl group include 1-naphthyl-2-pyridyl ketone, 2-naphthyl-2-pyridyl ketone, di-2-pyridyl ketone, 4-methylphenyl-2-pyridyl ketone, 4-fluorophenyl-2-pyridyl ketone, 4-chlorophenyl-2-pyridyl ketone, 4-bromophenyl-2-pyridyl ketone, 4-iodophenyl-2-pyridyl ketone, 4-nitrophenyl-2-pyridyl ketone, 4-(trifluoromethyl)phenyl-2-pyridyl ketone, 4-(trifluoromethoxy)phenyl-2-pyridyl ketone, and 4-biphenyl-2-pyridyl ketone.

[0017] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is an (E)-2-phenylethenyl group include 3-phenyl-1-(naphthalene-1-yl)-2-propen-1-one, 3-phenyl-1-(naphthalene-2-yl)-2-propen-1-one, 3-phenyl-1-(furan-2-yl)-2-propen-1-one, 3-phenyl-1-(furan-3-yl)-2-propen-1-one, 3-phenyl-1-(thiophene-2-yl)-2-propen-1-one, 3-phenyl-1-(thiophene-3 ... -(pyridin-2-yl)-2-propen-1-one, 3-phenyl-1-(pyridin-3-yl)-2-propen-1-one, 3-phenyl-1-(pyridin-4-yl)-2-propen-1-one, 3-phenyl-1-(2-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-(3-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-(4-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-(2-fluorophenyl)-2-propen-1-one, 3-phenyl-1-(3-fluorophenyl)-2-propen-1-one, phenyl)-2-propen-1-one, 3-phenyl-1-(4-fluorophenyl)-2-propen-1-one, 3-phenyl-1-(2-chlorophenyl)-2-propen-1-one, 3-phenyl-1-(3-chlorophenyl)-2-propen-1-one, 3-phenyl-1-(4-chlorophenyl)-2-propen-1-one, 3-phenyl-1-(2-bromophenyl)-2-propen-1-one, 3-phenyl-1-(3-bromophenyl)-2-propen-1-one, 3-phenyl-1-(4-bromophenyl)-2-propen- 1-one, 3-phenyl-1-(2-iodophenyl)-2-propen-1-one, 3-phenyl-1-(3-iodophenyl)-2-propen-1-one, 3-phenyl-1-(4-iodophenyl)-2-propen-1-one, 3-phenyl-1-(2-nitrophenyl)-2-propen-1-one, 3-phenyl-1-(3-nitrophenyl)-2-propen-1-one, 3-phenyl-1-(4-nitrophenyl)-2-propen-1-one, 3-phenyl-1-[2-(trifluoromethyl)phenyl]-2-propen-1-one,3-phenyl-1-[3-(trifluoromethyl)phenyl]-2-propen-1-one, 3-phenyl-1-[4-(trifluoromethyl)phenyl]-2-propen-1-one, 3-phenyl-1-(2-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-(3-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-(4-methoxyphenyl)-2-propen-1-one, 3-phenyl-1-[2-(trifluorometh Examples of the phenyl-1-(2-biphenyl)-2-propen-1-one include 3-phenyl-1-[3-(trifluoromethoxy)phenyl]-2-propen-1-one, 3-phenyl-1-[4-(trifluoromethoxy)phenyl]-2-propen-1-one, 3-phenyl-1-(2-biphenyl)-2-propen-1-one, 3-phenyl-1-(3-biphenyl)-2-propen-1-one, and 3-phenyl-1-(4-biphenyl)-2-propen-1-one.

[0018] Represented by general formula (1) applicable to the present invention, R 2Specific examples of the compound in which is an (E)-2-(4-fluorophenyl)ethenyl group include 3-(4-fluorophenyl)-1-(naphthalene-1-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(naphthalene-2-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(furan-2-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(furan-3-yl)-2-propen-1-one, and 3-(4-fluorophenyl)-1-(thiophene-2-yl)-2-propen-1-one. -one, 3-(4-fluorophenyl)-1-(thiophen-3-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(pyridin-2-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(pyridin-3-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(pyridin-4-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-methoxyphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-methoxyphenyl)-2-propen 1-propen-1-one, 3-(4-fluorophenyl)-1-(4-methoxyphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-fluorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-fluorophenyl)-2-propen-1-one, 1,3-bis(4-fluorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-chlorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-chlorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(4-chlorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-bromophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-bromophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(4-bromophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-iodophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-iodophenyl)-2-propen-1-one,3-(4-fluorophenyl)-1-(4-iodophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-nitrophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-nitrophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(4-nitrophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-[2-(trifluoromethyl)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-[3-(trifluoromethyl)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-[4-(trifluoromethyl)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-[4-(trifluoromethyl)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-methoxyphenyl)-2-propen-1-one, 3- (4-fluorophenyl)-1-(3-methoxyphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(4-methoxyphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-[2-(trifluoromethoxy)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-[3-(trifluoromethoxy)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-[4-(trifluoromethoxy)phenyl]-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-biphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-biphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(4-biphenyl)-2-propen-1-one, and the like.

[0019] Represented by general formula (1) applicable to the present invention, R 1 and R 2 Specific examples of compounds in which are bonded to form a ring include 9-fluorenone and 2-adamantanone.

[0020] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a hydrogen atom include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophene-2-yl)propan-1-ol, and 2,2,3,3,3-pentafluoro-1-(thiophene-2-yl)propan-1-ol. 2,2,3,3,3-pentafluoro-1-(thiophene-3-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-3-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-4-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro -1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-fluorophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)propan-1-ol, 2,2,3,3,3- Pentafluoro-1-(3-chlorophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-chlorophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-bromophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-bromophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-iodophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-iodophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-nitrophenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)propan-1 -ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethyl)phenyl]propan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethyl)phenyl]propan-1-ol, 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethyl)phenyl]propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-[2-(trifluoromethoxy)phenyl]propan-1-ol, 2,2,3,3,3-Pentafluoro-1-[3-(trifluoromethoxy)phenyl]propan-1-ol, 2,2,3,3,3- Examples of the pentafluoro-1-[4-(trifluoromethoxy)phenyl]propan-1-ol include 2,2,3,3,3-pentafluoro-1-[(1,1'-biphenyl)-2-yl]propan-1-ol, 2,2,3,3,3-pentafluoro-1-[(1,1'-biphenyl)-3-yl]propan-1-ol, and 2,2,3,3,3-pentafluoro-1-[(1,1'-biphenyl)-4-yl]propan-1-ol.

[0021] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a phenyl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-2-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-phenylpropan-1-ol, and 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-phenylpropan-1-ol. -1-(thiophen-2-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-3-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-2-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-3-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-4-yl)-1-phenylpropan-1-ol, 2,2,3,3,3- Pentafluoro-1,1-diphenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methylphenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-methylphenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-chlorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-chlorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-chlorophenyl)-1-phenylpropan-1-ol,3-Pentafluoro-1-(2-bromophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-bromophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-iodophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3- Pentafluoro-1-(4-iodophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-nitrophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethyl)phenyl]-1-phenylpropan-1-ol, 2,2,3 ,3,3-Pentafluoro-1-[3-(trifluoromethyl)phenyl]-1-phenylpropan-1-ol, 2,2,3,3,3-Pentafluoro-1-[4-(trifluoromethyl)phenyl]-1-phenylpropan-1-ol, 2,2,3,3,3-Pentafluoro-1-(2-methoxyphenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-methoxyphenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-methoxyphenyl)-1-phenyl Propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethoxy)phenyl]-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethoxy)phenyl]-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethoxy)phenyl]-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1´-biphenyl-2-yl)-1-phenylpropan-1-ol, 2,2,3,3,Examples of the fluorophenyl ether include 3-pentafluoro-1-(1,1'-biphenyl-3-yl)-1-phenylpropan-1-ol and 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-phenylpropan-1-ol.

[0022] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a 2-methoxyphenyl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-2-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-(2-methoxyphenyl)propan-1-ol, and 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-(2-methoxyphenyl)propan-1-ol. propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-2-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-3-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-2-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1- (Pyridin-3-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-4-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methylphenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-methylphenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-fluorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-chlorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-chlorophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(2-bromophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-bromophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4- 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-iodophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-iodophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)-1-(2-methoxyphenyl)propan-1-ol 2,2,3,3,3-pentafluoro-1-(3-nitrophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethyl)phenyl]-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethyl)phenyl]-1-(2-methoxyphenyl)propan-1-ol )propan-1-ol, 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethyl)phenyl]-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methoxyphenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methoxyphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-[2-(trifluoromethoxy)phenyl]-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-[3-(trifluoromethoxy)phenyl]-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-[4-(trifluoromethoxy)phenyl]-1-(2-methoxyphenyl)propan-1-ol, 2,2 , 3,3,3-pentafluoro-1-(1,1'-biphenyl-2-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-3-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-(2-methoxyphenyl)propan-1-ol, and the like.

[0023] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a 3-methoxyphenyl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-2-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-(3-methoxyphenyl)propan-1-ol, and propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-2-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-3-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-2-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1- (Pyridin-3-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-4-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methylphenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-methylphenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-fluorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-chlorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-chlorophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(2-bromophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-bromophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-bromophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-iodophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-iodophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)-1-(3-methoxyphenyl)propan-1-ol Propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-nitrophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethyl)phenyl]-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethyl)phenyl]-1-(3-methoxyphenyl)propane- 1-ol, 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethyl)phenyl]-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-methoxyphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethoxy)phenyl]-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,Examples of the fluorophenyl ether include 3-pentafluoro-1-[3-(trifluoromethoxy)phenyl]-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethoxy)phenyl]-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-2-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-3-yl)-1-(3-methoxyphenyl)propan-1-ol, and 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-(3-methoxyphenyl)propan-1-ol.

[0024] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a 4-methoxyphenyl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-2-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-(4-methoxyphenyl)propan-1-ol, propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-2-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-3-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-2-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1- (Pyridin-3-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(pyridin-4-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-methylphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-methylphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-fluorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-fluorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-chlorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-chlorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-chlorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(2-bromophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(3-bromophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-bromophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-iodophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-iodophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-iodophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-iodophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)-1-(4-methoxyphenyl)propan-1-ol 2,2,3,3,3-pentafluoro-1-(3-nitrophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethyl)phenyl]-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethyl)phenyl]-1-(4-methoxyphenyl)propan-1-ol 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethyl)phenyl]-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[2-(trifluoromethoxy)phenyl]-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethoxy)phenyl]-1-(4-methoxyphenyl)propan-1-ol, 2,2,Examples of the fluorophenyl ether include 3,3,3-pentafluoro-1-[4-(trifluoromethoxy)phenyl]-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-2-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-3-yl)-1-(4-methoxyphenyl)propan-1-ol, and 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)propan-1-ol.

[0025] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a pyridin-2-yl group include 2,2,3,3,3-pentafluoro-1-(naphthalene-1-yl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalene-2-yl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(pyridin-2-yl)propan-1-ol, and 2,2,3,3,3-pentafluoro-1,1-bis(pyridin-2-yl)propan-1-ol. propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-methylphenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-chlorophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2 ,3,3,3-Pentafluoro-1-(4-bromophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-iodophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-nitrophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-Pentafluoro-1-(4-nitrophenyl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-Pentafluoro 2,2,3,3,3-pentafluoro-1-[4-(trifluoromethoxy)phenyl]-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-(pyridin-2-yl)propan-1-ol, and the like.

[0026] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a (E)-2-phenylethenyl group include (E)-4,4,5,5,5-pentafluoro-3-(naphthalene-1-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(naphthalene-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(furan-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(furan-3-yl) -1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(thiophen-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(thiophen-3-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-3-yl)-1-phenylpent-1 -en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-4-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-methoxyphenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-methoxyphenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-methoxyphenyl)-1-phenylpent-1-en-3-ol, ( E)-4,4,5,5,5-pentafluoro-3-(2-fluorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-fluorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-fluorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-chlorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-(3-chlorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-chlorophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-bromophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-bromophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-bromophenyl) (E)-4,4,5,5,5-pentafluoro-3-(2-iodophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-iodophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-iodophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-nitrophenyl)-1-phenylpent-1-en-3-ol ol, (E)-4,4,5,5,5-pentafluoro-3-(3-nitrophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-nitrophenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[2-(trifluoromethyl)phenyl]-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[3-(trifluoromethyl)phenyl]-1-phenylpent-1-en-3-ol, (E )-4,4,5,5,5-pentafluoro-3-[4-(trifluoromethyl)phenyl]-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-methoxyphenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-methoxyphenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-methoxyphenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-[2-(trifluoromethoxy)phenyl]-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-[3-(trifluoromethoxy)phenyl]-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-[4-(trifluoromethoxy)phenyl]-1-phenylpent-1-en-3-ol, (E)-4 , 4,5,5,5-pentafluoro-3-(1,1'-biphenyl-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1'-biphenyl-3-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1'-biphenyl-4-yl)-1-phenylpent-1-en-3-ol, and the like.

[0027] Represented by general formula (5) applicable to the present invention, R 2Specific examples of the compound in which is a (E)-2-(4-fluorophenyl)ethenyl group include (E)-4,4,5,5,5-pentafluoro-3-(naphthalene-1-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(naphthalene-2-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(furan-2-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E) -4,4,5,5,5-pentafluoro-3-(furan-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(thiophen-2-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(thiophen-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-2-yl)-1-(4-fluorophenyl) Pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(pyridin-4-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-methoxyphenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-methoxyphenyl) (E)-4,4,5,5,5-pentafluoro-3-(4-methoxyphenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-fluorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-fluorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-(4-fluorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-chlorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-chlorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-chlorophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol , (E)-4,4,5,5,5-pentafluoro-3-(2-bromophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-bromophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-bromophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-iodophenyl)-1-(4-fluorophenyl)pent (E)-4,4,5,5,5-pentafluoro-3-(3-iodophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-iodophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-nitrophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-nitrophenyl)-1-(4 -fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-nitrophenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[2-(trifluoromethyl)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[3-(trifluoromethyl)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-Pentafluoro-3-[4-(trifluoromethyl)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-methoxyphenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-methoxyphenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(4-methoxyphenyl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[2-(trifluoromethoxy)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[2-(trifluoromethoxy)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro Fluoro-3-[3-(trifluoromethoxy)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-[4-(trifluoromethoxy)phenyl]-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1'-biphenyl-2-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1'-biphenyl-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1'-biphenyl-4-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, and the like. ,

[0028] Represented by general formula (5) applicable to the present invention, R 1 and R 2 Specific examples of compounds in which are bonded to form a ring include 9-(perfluoroethyl)-9H-fluoren-9-ol and 2-(pentafluoroethyl)-2-adamantanol.

[0029] Specific examples of bases applicable to the present invention include potassium hexamethyldisilazide (hereinafter, abbreviated as KHMDS), potassium tert-butoxide (hereinafter, abbreviated as tBuOK in the drawings), potassium diisopropylamide, sodium hexamethyldisilazide, sodium tert-butoxide, and sodium diisopropylamide. In terms of reactivity, potassium hexamethyldisilazide and potassium tert-butoxide are preferred, and the amount of the base used is preferably 1.1 to 3.0 moles per mole of the carbonyl compounds used in the reaction.

[0030] The amount of trifluoroethane used in the present invention is theoretically 1.0 mole or more per 1.0 mole of the carbonyl compound used in the reaction, but it is preferable to use 2.0 to 10.0 moles in order to complete the reaction.

[0031] The solvent applicable to the present invention is not particularly limited as long as it is inert to the reaction, and specific examples thereof include ether solvents such as diisopropyl ether, methyl tert-butyl ether, methylcyclopentyl ether, and tetrahydrofuran (hereinafter abbreviated as THF), aromatic hydrocarbon solvents such as toluene, ethylbenzene, and xylene, and aprotic polar solvents such as N,N-dimethylformamide (hereinafter abbreviated as DMF), N,N-dimethylacetamide, and N-methylpyrrolidine. Preferably, THF, DMF, and toluene are used alone or in combination, and the amount of each of them is 5 to 50 times by weight relative to the weight of the carbonyl compound and base used in the reaction.

[0032] The reaction temperature applicable to the present invention varies depending on the types of carbonyl compounds used in the reaction, the types of bases used, and the types of solvents used, but is usually within the temperature range of -50°C to 40°C. The mixing time of the carbonyl compounds, base and pentafluoroethane used in the present invention 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 seconds. It is preferable to carry out the reaction at a supply rate that results in a mixing time of 1.0 second or less, based on the volume of the mixing section of the micromixer and the total volume of the supplies per unit time. The reaction time after mixing of the carbonyl compound of the present invention, the base and trifluoroethane can be determined by the inner diameter and length of a microreactor (a device for carrying out chemical reactions in a microspace), and is usually within 10 seconds. In the present invention, the micromixer and microreactor used in the reaction may be a commonly available and commercially available one, or may be one designed suitably for the present invention. The micromixer and microreactor may be equipped with a heating or cooling device as necessary, and other auxiliary equipment for promoting the reaction may be appropriately added. The post-treatment after the reaction of the present invention can be carried out by a known method. For example, the reaction mixture may be neutralized with a saturated aqueous solution of ammonium chloride, extracted with an organic solvent such as diethyl ether, dried with a drying agent such as sodium sulfate, filtered, and concentrated 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. EXAMPLES

[0033] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0034] The following instruments were used for the analysis: 1 H-NMR (300MHz), 19 F-NMR (282MHz), 13 C-NMR (125.8 MHz): Burker Avance500US, Varian Mercury 300. HRMS: Shimadzu GCMS-QP5050A (SHIMADZU GCMS-QP5050A). ESI-MS: Shimadzu LCMS-2010EV (SHIMADZU LCMS-2010EV). IR: JASCO FT / IR-4100. Melting point: BUCHI Labortehnik AG-565.

[0035] For the reaction, a microflow reactor shown in FIG. 1 was used. In FIG. 1, A is a mass flow controller (Tokyo Rikakikai Flow Reactor FFX-1000G (only gas flow control function used)). B-1 and B-2 are syringe pumps (YMC Syringe Pump YSP-101) equipped with 5 mL gas-tight syringes. C is a micromixer (Sugiyama Shoji's four-way micro swirl mixer), made of SUS316, with an inner diameter of 0.8 mm, length of 12 mm, and volume of 60 μL. D is 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.

[0036] Each part was connected with a 1 / 16 inch joint. The CF3CF2H supply line shown in FIG. 1 was a pipe made of SUS316 and having an inner diameter of 0.8 mm. The supply lines for the solutions of KHMDS and tBuOK shown in Figure 1 as "(KHMDS or tBuOK) in solvent" and the substituent R shown in Figure 1 as "1,3,5 in solvent" 1 ,R 2The supply line for the carbonyl compound solution was a PTFE pipe with an inner diameter of 0.8 mm. The supply lines for the KHMDS or tBuOK solution and the carbonyl compound solution may supply the two separately or together. When KHMDS and tBuOK are used as a mixture, they may be mixed in advance, or a mixer capable of mixing the two liquids and another syringe pump may be added before the micromixer, and each may be supplied separately.

[0037] Example 1 Preparation of 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) [ka] 4-Bromobenzaldehyde (1a) (222 mg, 1.20 mmol) was dissolved in anhydrous DMF (2.0 mL) to prepare a 4-bromobenzaldehyde solution (0.60 M) which was placed in a 5 mL gas-tight syringe and attached to a syringe pump (B-1). Similarly, potassium tert-butoxide (269 mg, 2.40 mmol) was dissolved in DMF (4 mL) to prepare a potassium tert-butoxide solution (0.60 M) which was placed in another gas-tight syringe and attached to a syringe pump (B-2). 0.33mL / min of 4-bromobenzaldehyde solution and 0.50mL of potassium tert-butoxide solution were supplied to mixer C and microreactor D (D-1 was used) cooled to -10℃ in advance using a thermostatic bath, while pentafluoroethane (0.1MPa) was supplied to them at 15mL / min (pentafluoroethane / 4-bromobenzaldehyde=3.10 / 1 mol / mol). When the supply of pentafluoroethane became stable, the distillate from the outlet of the microreactor (D) was quenched with a saturated aqueous ammonium chloride solution for 1 minute. Next, extraction was performed with ethyl ether, and the obtained organic layer was washed with saturated saline, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product of the target product. During a stable reaction, the mixing time in the micromixer was 0.22 seconds, and the reaction time in the microreactor was 3.1 seconds.

[0038] The obtained crude product was subjected to HPLC analysis using benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a), was 92%. The obtained crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target compound, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) (54.4 mg, 0.178 mmol, yield 90%) as a white solid.

[0039] The analysis results are shown below. 1 H-NMR (300MHz, CDCl3) δ:7.56(d,J=8.2Hz,2H),7.34(D,J=8.2Hz,2H),5.15-5.06(m,1H),2.53-2.49(m,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.2(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-130.0(dd, 2 J F-F , 3 J F-F =275.9,17.2Hz,1F) ppm. MS(ESI,m / z)306[M+H] + .

[0040] Examples 2 to 8 Preparation of 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) The reaction was carried out using the same microflow reactor as in Example 1, 4-bromobenzaldehyde solution (0.60 M) and potassium tert-butoxide solution (0.60 M), and varying the supply rate and temperature of each reagent. The results are shown in Table 1.

[0041] [Table 1]

[0042] Example 9 Preparation of 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) The same reaction apparatus as in Example 1 was used, but the 4-bromobenzaldehyde solution (0.60 M) was replaced with a 4-bromobenzaldehyde solution (0.90 M) and fed at 0.30 mL / min, potassium tert-butoxide solution (0.60 M) was fed at 0.30 mL / min, and pentafluoroethane (0.1 MPa) was fed at 20.0 mL / min, and the reaction was carried out at -10. The obtained crude product was analyzed by using benzotrifluoride as an internal standard substance. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a), was 89%.

[0043] Examples 10 to 21 Reactions of various aldehydes The same reaction apparatus as in Example 1 was used, but the microreactor was changed from D-1 to D-2, and the 4-bromobenzaldehyde solution (0.60 M) was replaced with a solution of one of the aldehydes (0.60 M) shown in Table 2. The results are shown in Table 2.

[0044] [Table 2]

[0045] 1) 2,2,3,3,3-Pentafluoro-1-phenylpropan-1-ol (2b) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (40.3 mg, 0.178 mmol, yield 90%). 1H-NMR (300MHz, CDCl3) δ: 7.45 (brs, 5H), 5.18-5.09 (m, 1H), 2.44 (d, J = 4.4Hz, 1H) ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.3(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.9(dd, 2 J F-F , 3 J F-F =275.9,17.2Hz,1F) ppm. MS(ESI,m / z)227[M+H] + . 2) 2,2,3,3,3-Pentafluoro-1-(4-methoxyphenyl)propan-1-ol (2c) The crude product was purified by silica gel column chromatography (hexane / diethyl ether=1 / 1 vol / vol) to obtain the target product as a white solid (46.2 mg, 0.180 mmol, yield 91%). 1 H NMR (300MHz, CDCl3)δ:7.36(d,J=8.8Hz,2H),6.92(d-lile,J=8.8Hz,2H),5.08-4.99(m,1H),3.81(s,3H),2.75(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.7(dd, 2 J F-F , 3 J F-F =274.1,8.6Hz,1F),-129.9(dd, 2 J F-F , 3 J F-F =275.0,16.4Hz,1F) ppm. MS(ESI,m / z)257[M+H] + . 3)2,2,3,3,3-Pentafluoro-1-[(1,1´-biphenyl)-4-yl]propan-1-ol (2d) The crude product was purified by silica gel column chromatography (hexane / diethyl ether=4 / 1 vol / vol) to obtain the target product as a white solid (52.7 mg, 0.174 mmol, yield 88%). 1 H-NMR (300MHz, CDCl3) δ:7.67-7.37(m,9H),5.23-5.14(m,1H),2.56(d,J=4.1Hz,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.2(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-130.0(dd, 2 J F-F , 3 J F-F =275.9,17.2Hz,1F) ppm. MS(ESI,m / z)303[M+H] + . 4) 2,2,3,3,3-Pentafluoro-1-(4-chlorophenyl)propan-1-ol (2e) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a white solid (46.5 mg, 0.178 mmol, yield 90%). 1 H-NMR (300MHz, CDCl3) δ: 7.41 (brs, 4H), 5.18-5.08 (m, 1H), 2.47 (d, J = 4.1Hz, 1H) ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.3(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.8(dd, 2 J F-F , 3 JF-F =275.9,15.5Hz,1F) ppm. MS(ESI,m / z)261[M+H] + . 5) 2,2,3,3,3-Pentafluoro-1-(4-iodophenyl)propan-1-ol (2f) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a white solid (64.0 mg, 0.182 mmol, yield 92%). 1 H-NMR (300MHz, CDCl3) δ:7.76(d,J=8.2Hz,2H),7.21(d,J=8.2Hz,2H),5.14-5.05(m,1H),2.52-2.49(m,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.2(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.9(dd, 2 J F-F , 3 J F-F =275.9,15.5Hz,1F) ppm. MS(ESI,m / z)352[M+H] + . 6) 2,2,3,3,3-Pentafluoro-1-(4-fluorophenyl)propan-1-ol (2g) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (42.1 mg, 0.172 mmol, yield 87%). 1 H-NMR(300MHz, CDCl3)δ:7.46(t-lile,J=6.5Hz,2H),7.12(t-like,J=8.5Hz,2H),5.18-5.09(m,1H),2.45(d,J=4.4Hz,1H)ppm. 19F-NMR(282MHz,CDCl3)δ:-81.6(s,3F),-111.9(s,1F),-122.5(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.7(dd, 2 J F-F , 3 J F-F =275.9,15.5Hz,1F) ppm. MS(ESI,m / z)245[M+H] + . 7) 2,2,3,3,3-Pentafluoro-1-[4-(trifluoromethoxy)phenyl]propan-1-ol (2h) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (52.8 mg, 0.170 mmol, yield 86%). 1 H-NMR (300MHz, CDCl3) δ:7.52(d,J=8.5Hz,2H),7.27(d,J=7.9Hz,2H),5.21-5.12(m,1H),2.60(d,J=4.4Hz,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-58.3(s,3F),-81.6(s,3F),-122.2(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.9(dd, 2 J F-F , 3 J F-F =276.7,16.4Hz,1F)ppm. MS(ESI,m / z)311[M+H] + . 8) 2,2,3,3,3-Pentafluoro-1-(naphthalen-2-yl)propan-1-ol (2i) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a white solid (49.8 mg, 0.180 mmol, yield 91%). 1 H-NMR (300MHz, CDCl3) δ:7.95-7.87(m,4H),7.59-7.53(m,3H),5.36-5.26(m,1H),2.58(d,J=4.7Hz,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.7(s,3F),-122.1(dd, 2 J F-F , 3 J F-F =275.9,6.9Hz,1F),-129.6(dd, 2 J F-F , 3 J F-F =275.9,15.5Hz,1F) ppm. MS(ESI,m / z)277[M+H] + . 9) 2,2,3,3,3-Pentafluoro-1-(naphthalen-1-yl)propan-1-ol (2j) The crude product was purified by silica gel column chromatography (hexane / acetone=7 / 1 vol / vol) to obtain the target product as a yellow solid (44.8 mg, 0.162 mmol, yield 82%). 1 H-NMR (300MHz, CDCl3)δ:8.02(d,J=7.6Hz,1H),7.94-7.91(m,2H),7.82(d,J=7.4Hz,1H),7.61-7.51(m,3H),6.06-5.97(m,1H),2.74(brs,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.8(s,3F),-122.1(dd, 2 J F-F , 3 J F-F =274.1,6.9Hz,1F),-130.5(dd, 2 J F-F , 3 JF-F =274.1,17.2Hz,1F)ppm. 13 C-NMR(126MHz,CDCl3)δ:133.8,131.4,130.4,130.2,129.1,127.0,126.5,126.1,125.3,122.8,119.4(qt, 1 J C-F , 2 J C-F =285.5,34.4Hz),116.0-111.0(m),67.7(dd, 2 J C-Fa , 2 J C-Fb =29.1,21.8Hz) ppm. ATR-FTIR(KBr):n=3465,3059,1514,1351,1185,1134,1080,1026,790,720cm -1 . HRMS(ESI)m / z:[MH] - calcd.for C 13 H8F5O;275.0495,found:275.0497. Melting point: 45.5-46.3℃. 10) 2,2,3,3,3-Pentafluoro-1-(furan-2-yl)propan-1-ol (2k) The crude product was purified by silica gel column chromatography (hexane / diethyl ether=4 / 1 vol / vol) to obtain the target product as a yellow liquid (27.8 mg, 0.129 mmol, yield 65%). 1 H-NMR(300MHZ, CDCl3)δ:7.49(s,1H),6.54(s,1H),6.44(s,1H),5.20-5.10(m,1H),2.59(d,J=7.9Hz,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-82.4(s,3F),-123.2(dd, 2 J F-F , 3 J F-F =274.1,6.9Hz,1F),-129.3(dd, 2 J F-F, 3 J F-F =275.0,16.4Hz,1F) ppm. 13 C-NMR(126MHz,CDCl3)δ:146.8,144.0,118.94(qt, 1 J C-F , 2 J C-F =286.6,35.2Hz),115.1-110.1(m),111.0,110.8,66.5(q, 2 J C-F =17.3Hz) ppm. ATR-FTIR(KBr):n=3407,2927,1507,1363,1192,1138,1015,929,809,744cm -1 . HRMS(ESI)m / z:[M+H] + calcd.for C7H6F5O2;217.0288,found:217.0278. 11) 2,2,3,3,3-Pentafluoro-1-(thiophen-2-yl)propan-1-ol (2m) The crude product was purified by silica gel column chromatography (hexane / diethyl ether=4 / 1 vol / vol) to obtain the target product as a yellow liquid (31.7 mg, 0.137 mmol, yield 69%). 1 H-NMR (300MHz, CDCl3)δ:7.43(d,J=4.4Hz,1H),7.21(brs,1H),7.08-7.05(m,1H),5.39(dd,J=16.5,5.9Hz,1H),2.69(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-81.8(s,3F),-122.1(dd, 2 J F-F , 3 J F-F =274.1,6.9Hz,1F),-130.5(dd, 2 J F-F , 3 J F-F =274.1,17.2Hz,1F)ppm. 13C-NMR(126MHz,CDCl3)δ:136.0,128.2,127.7,127.1,119.1(qt, 1 J C-F , 2 J C-F =287.0,35.4Hz),115.1-110.1(m),68.5(q, 2 J C-F =17.6Hz) ppm. ATR-FTIR(neat):n=3426,2923,1432,1355,1208,1131,1023,809,708cm -1 . HRMS(ESI)m / z:[MH] - calcd. for C7H4F5OS;230.9903,found:230.9911.

[0046] Example 21 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) [ka] Benzophenone (3a) (219 mg, 1.20 mmol) was dissolved in anhydrous DMF (2.0 mL) to prepare a benzophenone solution (0.60 M) in a 5 mL gas-tight syringe and attached to a syringe pump (B-1). Similarly, potassium tert-butoxide (269 mg, 2.40 mmol) was dissolved in DMF (4 mL) to prepare a potassium tert-butoxide solution (0.60 M) in another gas-tight syringe and attached to a syringe pump (B-2).

[0047] Acetophenone solution was supplied at 0.30 mL / min and potassium tert-butoxide solution at 0.60 mL at room temperature to mixer C and microreactor D (D-1 was used), while pentafluoroethane (0.1 MPa) was supplied at 15 mL / min (pentafluoroethane / benzophenone=3.41 / 1 mol / mol). When the supply of pentafluoroethane became stable, the distillate from the outlet of microreactor D-1 was quenched with saturated aqueous ammonium chloride solution for 1 minute. Next, extraction was performed with ethyl ether, and the obtained organic layer was washed with saturated saline, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product of the target product. During a stable reaction, the mixing time in the micromixer was 0.23 seconds, and the reaction time in the microreactor was 1.2 seconds.

[0048] The obtained crude product was subjected to HPLC analysis using benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a), was 94%. The obtained crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target compound, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) (50.0 mg, 0.166 mmol, yield 92%), as a white solid.

[0049] The analysis results are shown below. 1 H-NMR (300MHz, CDCl3) δ: 7.63-7.53 (m, 4H), 7.41-7.32 (m, 6H), 2.95-2.93 (m, 1H) ppm. 19 F-NMR (282MHz, CDCl3) δ: -77.6 (brs, 3F), -116.9 (brs, 2F) ppm. MS(ESI,m / z)301[MH] - .

[0050] Examples 22-28 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) The reaction was carried out using the same microflow reactor as in Example 21, a benzophenone solution (0.60 M) and a potassium tert-butoxide solution (0.60 M), and varying the supply rate and temperature of each reagent. The results are shown in Table 3.

[0051] [Table 3]

[0052] Example 29 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) The reaction was carried out at room temperature using the same reaction apparatus as in Example 21, except that the benzophenone solution (0.60 M) was replaced with a benzophenone solution (0.90 M) at 0.33 mL / min, potassium tert-butoxide solution (0.60 M) at 0.66 mL / min, and pentafluoroethane (0.1 MPa) at 25.0 mL / min. The crude product was analyzed by HPLC using benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a), was 91%.

[0053] Example 30 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) The reaction was carried out at room temperature using the same reaction apparatus as in Example 21, except that the benzophenone solution (0.60 M) was replaced with a benzophenone solution (1.20 M) supplied at 0.33 mL / min, potassium tert-butoxide solution (0.60 M) supplied at 0.66 mL / min, and pentafluoroethane (0.1 MPa) supplied at 25.0 mL / min. The crude product obtained was analyzed by HPLC using benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target compound, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a), was 73%.

[0054] Examples 31 to 41 Reactions of various ketones The same reaction apparatus as in Example 21 was used, and the same reaction procedure as in Example 21 was carried out, except that the benzophenone solution (0.60 M) was replaced with a solution (0.60 M) of each of the aldehydes shown in Table 4. The results are shown in Table 4.

[0055] [Table 4]

[0056] 1) 2,2,3,3,3-Pentafluoro-1-phenyl-1-(p-tolyl)propan-1-ol (4b) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (49.1 mg, 0.155 mmol, yield 86%). 1 H-NMR (300MHz, CDCl3)δ:7.55(d,J=6.8Hz,2H),7.43(d,J=7.6Hz,2H),7.35-7.33(m,3H),7.15(d,J=7.9Hz,2H),2.81(s,1H),2.34(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-77.5(s,3F),-116.9(s,2F)ppm. MS(ESI,m / z)315[MH] - . 2) 2,2,3,3,3-Pentafluoro-1,1-bis(4-methoxyphenyl)propan-1-ol (4c) The crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (60.8 mg, 0.167 mmol, yield 93%). 1H-NMR (300MHz, CDCl3) δ:7.45(d,J=8.8Hz,4H),6.85(d,J=8.8Hz,4H),3.79(s,6H),2.89(s,1H)ppm. 19 F-NMR(282 MHz, CDCl3)δ:-77.6(s,3F),-117.0(s,2F)ppm. MS(ESI,m / z)361[MH] - . 3) 2,2,3,3,3-Pentafluoro-1-(2-chlorophenyl)-1-phenylpropan-1-ol (4d) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=2 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (51.7 mg, 0.153 mmol, yield 85%). 1 H-NMR (300MHz, CDCl3) δ:7.99(d,J=7.1Hz,1H),7.43-7.35(m,8H),4.03(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-76.7(s,3F),-114.0(d, 2 J F-F =275.9Hz,1F),-116.6(d, 2 J F-F =275.9Hz,1F)ppm. 13 C-NMR(126MHz,CDCl3)δ:138.1,137.2,133.3,132.6,130.1,129.1(t, 3 J C-F =5.9Hz),128.7,128.0,127.9,126.6,119.3(qt, 1 J C-F =288.4,35.0Hz),117.7-112.6(m),80.6(t, 2 J C-F =23.2Hz) ppm. ATR-FTIR(neat):n=3555,3067,1452,1336,1223,1134,1050,910,863,755cm -1 . HRMS(ESI)m / z:[MH] - calcd.for C 15 H9CLF5O;335.0262,found:335.0258. 4) 2,2,3,3,3-Pentafluoro-1-(3-chlorophenyl)-1-phenylpropan-1-ol (4e) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=2 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (52.7 mg, 0.157 mmol, yield 87%). 1 H-NMR (300MHz, CDCl3) δ:7.63(s,1H),7.59-7.56(m,2H),7.46(d,J=7.1Hz,1H),7.39-7.29(m,5H),2.97(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-77.6(s,3F),-116.4(d, 2 J F-F =279.3Hz,1F),-117.6(d, 2 J F-F =279.3Hz,1F)ppm. MS(ESI,m / z)335[MH] - . 5) 2,2,3,3,3-Pentafluoro-1-(4-chlorophenyl)-1-phenylpropan-1-ol (4f) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=2 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (56.3 mg, 0.167 mmol, yield 93%). 1 H-NMR (300MHz, CDCl3) δ: 7.56-7.52 (m, 4H), 7.38-7.32 (m, 5H), 2.92 (s, 1H) ppm. 19 F-NMR(282MHz,CDCl3)δ:-77.6(s,3F),-116.5(d, 2 J F-F=279.3Hz,1F),-117.7(d, 2 J F-F =277.6Hz,1F)ppm. MS(ESI,m / e)335[MH] - . 6) 2,2,3,3,3-Pentafluoro-1-(4-bromophenyl)-1-phenylpropan-1-ol (4g) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (62.4 mg, 0.164 mmol, yield 91%). 1 H-NMR (300MHz, CDCl3) δ: 7.53-7.35 (m, 9H), 2.90 (d-like, J=6.5Hz, 1H) ppm. 19 F-NMR(282MHZ,CDCl3)δ:-77.5(s,3F),-116.4(d, 2 J F-F =277.6Hz,1F),-117.6(d, 2 J F-F =277.6Hz,1F)ppm. MS(ESI,m / z)404[M+Na] + . 7) 2,2,3,3,3-Pentafluoro-1-(4-nitrophenyl)-1-phenylpropan-1-ol (4h) The crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a yellow solid (47.6 mg, 0.134 mmol, yield 76%). 1 H-NMR (300MHz, CDCl3)δ:8.18(d,J=8.8Hz,2H),7.76(d,J=8.2Hz,2H),7.54-7.52(m,2H),7.39-7.37(m,3H),3.16(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-77.5(s,3F),-115.9(d, 2 J F-F=279.3Hz,1F),-118.0(d, 2 J F-F =279.3Hz,1F)ppm. MS(ESI,m / z)346[MH] - . 8) 2,2,3,3,3-Pentafluoro-1-[4-(trifluoromethyl)phenyl]-1-phenylpropan-1-ol (4i) The crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a colorless transparent liquid (58.1 mg, 0.157 mmol, yield 87%). 1 H-NMR (300MHz, CDCl3) δ:7.70(d,J=8.5Hz,2H),7.61(d,J=8.2Hz,2H),7.56-7.53(M,2H),7.41-7.33(m,3H),2.99(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-63.3(s,3F),-77.5(s,3F),-116.3(d, 2 J F-F =279.3Hz,1F),-117.8(d, 2 J F-F =277.6Hz,1F)ppm. MS(ESI,m / z)369[MH] - . 9) 9-(Perfluoroethyl)-9H-fluoren-9-ol (4j) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a white solid (48.7 mg, 0.162 mmol, yield 90%). 1 H-NMR (300MHz, CDCl3)δ:7.73-7.63(m,4H),7.48(t-like,J=7.4Hz,2H),7.35(t-lile,J=7.5Hz,2H),2.78(s,1H)ppm. 19F-NMR(282MHz, CDCl3)δ:-79.4(s,3F),-122.2(s,2F)ppm. MS(ESI,m / z)299[MH] - . 10) 2,2,3,3,3-Pentafluoro-1,1-bis(pyridin-2-yl)propan-1-ol (4k) The crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 1 vol / vol) to obtain the target product as a white solid (46.4 mg, 0.153 mmol, yield 85%). 1 H-NMR (300MHz, CDCl3) δ:8.60-8.58(m,2H),8.24(d-like,J=7.9Hz,2H),7.79-7.73(m,2H),7.58(s,1H),7.31-7.26(m,2H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-78.5(s,3F),-118.3(s,2F)ppm. MS(ESI,m / z)305[M+Na] + . 11) 2-(Pentafluoroethyl)-2-adamantanol (4l) The crude product was purified by silica gel column chromatography (hexane / diethyl ether=4 / 1 vol / vol) to obtain the target product as a white solid (41.4 mg, 0.153 mmol, yield 85%). 1 H-NMR (300MHz, CDCl3) δ: 2.27-2.12 (m, 6H), 1.92-1.75 (m, 7H), 1.61 (d, J = 12.4Hz, 2H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-78.6(s,3F),-117.4(s,2F)ppm. MS(ESI,m / z)269[MH] - .

[0057] Example 42 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) [ka] Using the same microflow reactor as in Example 21, a chalcone solution (0.3 M) obtained by dissolving chalcone (5a) (125 mg, 0.60 mmol) in anhydrous toluene (2.0 mL) was placed in a 5 mL gas-tight syringe and attached to a syringe pump (B-1). Similarly, a KHMDS solution (0.3 M) obtained by dissolving KHMDS (239 mg, 1.20 mmol) in toluene (4.0 mL) was placed in another gas-tight syringe and attached to a syringe pump (B-2).

[0058] The chalcone solution was fed at a rate of 0.33 mL / min and the KHMDS solution was fed at a rate of 0.50 mL / min to the mixer C and the microreactor D (D-1 was used) at room temperature, while pentafluoroethane (0.1 MPa) was fed at 7.5 mL / min (pentafluoroethane / chalcone=3.10 / 1 mol / mol). When the supply of pentafluoroethane became stable, the distillate from the outlet of the microreactor D-1 was quenched with a saturated aqueous ammonium chloride solution for 1 minute. Then, the mixture was extracted with ethyl ether, and the resulting organic layer was washed with saturated saline, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product of the target product. During a stable reaction, the mixing time in the micromixer was 0.43 seconds, and the reaction time in the microreactor was 2.3 seconds.

[0059] The obtained crude product was subjected to HPLC analysis using benzotrifluoride as an internal standard. 19 F-NMR measurement revealed that the yield of the target product, (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a), was 90%. The obtained crude product was purified by silica gel column chromatography (hexane / dichloromethane=1 / 2 vol / vol) to obtain the target product as a white solid (29.0 mg, 0.0883 mmol, yield 89%).

[0060] The analysis results are shown below. 1 H-NMR (300MHz, CDCl3) δ:7.65(d,J=7.1Hz,2H),7.44-7.29(m,8H),6.86(brs,2H),2.74(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-78.2(s,3F),-121.0(d, 2 J F-F =279.3Hz,1F),-122.0(d, 2 J F-F =277.6Hz,1F)ppm. MS(ESI,m / z)327[MH] - .

[0061] Examples 43-45 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) The reaction was carried out in the same microflow reactor as in Example 42, using a toluene solution of chalcone (0.30 M) and a toluene solution of KHMDS (0.3 M) at room temperature while changing the supply rate and temperature of each reagent. The results are shown in Table 5.

[0062] [Table 5]

[0063] Example 46 The same reaction apparatus as in Example 42 was used, and the same operation as in Example 43 was carried out except that the reaction temperature in Example 43 was changed from room temperature to -10°C, thereby obtaining the target product (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) in a yield of 90%. Examples 47-49 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) The reaction was carried out in the same manner as in Example 42, except that the KHMDS concentration was changed to 0.6 M, the supply rate was changed to 0.30 mL / min, the supply rate of the chalcone solution (0.30 M) was changed to 0.30 mL / min, the supply rate of the pentafluoroethane (0.1 MPa) was changed to 25 mL / min, and the solvent type was changed. The results are shown in Table 6.

[0064] [Table 6]

[0065] Example 50 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) The same reaction apparatus as in Example 42 was used, and the same operation as in Example 47 was carried out except that tBuOK (0.6 M) was used instead of KHMDS solution (0.6 M), to obtain the target compound (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) in a yield of 45%. Examples 51 to 55 Reactions of various chalcones The target product was obtained by the same operation as in Example 42, except that the microflow reactor of Example 42 was used and the chalcones shown in Table 7 were used instead. Note that in Example 55, the reaction was carried out using THF as the solvent. The results are shown in Table 7.

[0066] [Table 7]

[0067] 1) (E)-4,4,5,5,5-Pentafluoro-3-(4-methoxyphenyl)-1-phenylpent-1-en-3-ol (6b) The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a white solid (31.1 mg, 0.0871 mmol, yield 88%). 1H-NMR (300MHz, CDCl3)δ:7.55(d,J=9.1Hz,2H),7.44-7.29(m,5H),6.93(d,J=9.1Hz,2H),6.84(brs,2H),3.82(s,3H),2.69(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-78.2(s,3F),-121.1(d, 2 J F-F =277.6Hz,1F),-122.1(d, 2 J F-F =277.6Hz,1F)ppm. MS(ESI,m / z)357[MH] - . 2) (E)-4,4,5,5,5-Pentafluoro-3-(4-chlorophenyl)-1-phenylpent-1-en-3-ol (6c) The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a white solid (31.3 mg, 0.0861 mmol, yield 87%). 1 H-NMR (300MHz, CDCl3) δ:7.58(d,J=8.5Hz,2H),7.43-7.28(m,7H),6.82(brs,2H),2.84-2.81(m,1H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-78.1(s,3F),-121.6(s,2F)ppm. MS(ESI,m / z)361[MH] - . 3) (E)-4,4,5,5,5-Pentafluoro-3-(4-chlorophenyl)-1-phenylpent-1-en-3-ol (6d) The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target compound as a colorless transparent liquid (35.1 mg, 0.0861 mmol, yield 87%). 1H-NMR (300MHz, CDCl3) δ: 7.56-7.49 (m, 4H), 7.44-7.29 (m, 5H), 6.81 (brs, 2H), 2.66 (s, 1H) ppm. 19 F-NMR(282MHz, CDCl3)δ:-78.1(s,3F),-121.6(s,2F)ppm. MS(ESI,m / z)406[MH] - . 4) (E)-4,4,5,5,5-Pentafluoro-1,3-bis(4-fluorophenyl)pent-1-en-3-ol (6e) The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a yellow liquid (25.2 mg, 0.0693 mmol, yield 70%). 1 H-NMR(300MHz,CDCl3)δ:7.61(dd,J=8.8,5.3Hz,2H),7.41-7.36(m,2H),7.12 -7.01(m,4H),6.80(d,J=15.9Hz,1H),6.73(d,J=16.2Hz,1H),2.71(s,1H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-78.2(s,3F),-113.1--113.0(m,1F),-113.6--113.5(m,1F),-121.7(s,2F)ppm. MS(ESI,m / z)363[NH] - . 5) (E)-4,4,5,5,5-Pentafluoro-3-(4-nitrophenyl)-1-phenylpent-1-en-3-ol (6f) The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate=9 / 1 vol / vol) to obtain the target product as a yellow solid (26.2 mg, 0.0713 mmol, yield 72%). 1H-NMR (300MHz, CDCl3)δ:8.26(d,J=9.1Hz,2H),7.84(d,J=8.8Hz,2H),7.43-7.30(m,5H),6.89-6.78(m,2H),2.89(s,1H)ppm. 19 F-NMR(282MHz,CDCl3)δ:-78.1(s,3F),-120.9(d, 2 J F-F =279.3Hz,1F),-122.1(d, 2 J F-F =279.3Hz,1F)ppm. MS(ESI,m / z)372[MH] - . [Industrial Applicability]

[0068] The pentafluoroethyl group-containing compound obtained by the method of the present invention is useful as a production intermediate in the fields of medicines, agrochemicals and electronic materials. [Explanation of symbols]

[0069] A: Mass flow controller B-1, B-2: Syringe pump C: Micro mixer D: Microreactor

Claims

1. The following general formula (1) 【Chemistry 12】 [In formula (1), R １ represents a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a furan-3-yl group, a thiophene-2-yl group, a thiophene-3-yl group, a pyridin-2-yl group, a pyridin-3-yl group, a pyridin-4-yl group, or a group represented by the following general formula (2): 【Chemistry 13】 (In formula (2), R ３ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R ２ represents a hydrogen atom, a pyridin-2-yl group, or a group represented by the following general formula (3): 【Chemistry 14】 (In formula (3), R ４ represents a hydrogen atom or a methoxy group), or the following general formula (4): 【Chemistry 15】 (In formula (4), R ５ represents a hydrogen atom or a methoxy group, and R １ and R ２ may be bonded to form a ring. and carbonyl compounds represented by the formula: potassium hexamethyldisilazide and / or potassium tert-butoxide, Pentafluoroethane, reacting in the presence of an organic solvent, The following general formula (5) 【Chemistry 16】 [In formula (5), R １ represents a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophene-2-yl group, a pyridin-2-yl group, or a group represented by the following general formula (6): 【Chemistry 17】 (In formula (6), R ３ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R ２ represents a hydrogen atom, a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophene-2-yl group, a pyridin-2-yl group, or a group represented by the following general formula (7): 【Chemistry 18】 (In formula (7), R ４ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group), or a group represented by the following general formula (8): 【Chemistry 19】 (In formula (8), R ５ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group, and R １ and R ２ may be bonded to form a ring. A method for producing a pentafluoroethyl group-containing compound represented by the formula: a carbonyl compound supplied from a supply line for the carbonyl compound solution; potassium tert-butoxide and / or potassium hexamethyldisilazide supplied from a supply line for the potassium tert-butoxide and / or potassium hexamethyldisilazide solution; The mixture is mixed with pentafluoroethane supplied from the pentafluoroethane supply line using a micromixer for a period of 0.001 to 1 second, Then, the reaction is carried out in a microreactor within 10 seconds. A method for producing a pentafluoroethyl group-containing compound.

2. 2. The method for producing a pentafluoroethyl group-containing compound according to claim 1, wherein the organic solvent is toluene, tetrahydrofuran, and / or N,N-dimethylformamide.

3. 3. The method for producing a pentafluoroethyl group-containing compound according to claim 1, wherein the reaction temperature is in the range of -10°C to 40°C.

4. 4. The method for producing a pentafluoroethyl group-containing compound according to claim 1, further comprising using a micromixer having a structure capable of simultaneously mixing three components.

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