JP2022166441A - Method for producing pentafluoroethyl group-containing compound - Google Patents

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

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 for the production of pharmaceuticals and agricultural chemicals or an intermediate for the production of electronic materials.

Pentafluoroethyl anions have been known to be unstable and are known to decompose at temperatures of -50°C or higher.
Therefore, a method of using (pentafluoroethyl)trimethylsilane in the reaction is known (see, for example, Non-Patent Document 1).
In addition, using a microflow reactor, a mixture of pentafluoroethyl iodide and carbonyl compounds was reacted with methyllithium at 0°C, and pentafluoroethyliodide and methyllithium were reacted at -50°C or lower. A method is known in which a trifluoroethyl anion is generated and then immediately reacted with a carbonyl compound (see, for example, Non-Patent Document 2).

The method described in Non-Patent Document 1 allows the reaction 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 is necessary to use unstable methyllithium, and lithium iodide produced as a by-product of the reaction of pentafluoroethyl iodide and methyllithium is generated in the microflow reactor. There is a problem of precipitation and causing clogging.

Uneyama, K, et al., J. Am. Fluor. Chem. 2008, 129, 550. Jun-ich Yoshida et al., Org. & Biomol. Chem. 2011, 9, 7559.

An object of the present invention is to provide a practical production method, that is, an economical and safe method, in which pentafluoroethane is used as a raw material, pentafluoroethyl anions are generated in a general-purpose solvent, and reacted with a carbonyl compound to obtain a trifluoroethyl group-containing compound. and to provide an industrial manufacturing method.

The present inventors have made intensive studies on a method for obtaining carbonyl compounds using pentafluoroethane as a raw material. and a carbonyl compound in a short time of 1.0 second or less, the desired trifluoroethyl group-containing compound can be obtained, thereby completing the present invention.

［式（１）中、Ｒ^１はナフタレン－１－イル基、ナフタレン－２－イル基、フラン－２－イル基、フラン－３－イル基、チオフェン－２－イル基、チオフェン－３－イル基、ピリジン－２－イル基、ピリジン－３－イル基、ピリジン－４－イル基、又は下記一般式（２）

（式（２）中、Ｒ^３は、水素原子、メチル基、ハロゲン原子、ニトロ基、トリフルオロメチル基、メトキシ基、又はトリフルオロメトキシ基を示す）を示し、Ｒ^２は水素原子、ピリジン－２－イル基、又は下記一般式（３）

（式（３）中、Ｒ^４は、水素原子、又はメトキシ基を示す）、又は下記一般式（４）

（式（４）中、Ｒ^５は、水素原子、又はメトキシ基を示す）を示し、Ｒ^１とＲ^２は結合して環を形成しても良い］
で表されるカルボニル化合物類を、有機溶剤存在下、マイクロミキサー及びマイクロリアクターを用い、塩基及びペンタフルオロエタンを供給かつ混合し、反応させることを特徴とする、下記一般式（５）

［式（５）中、Ｒ^１はナフタレン－１－イル基、ナフタレン－２－イル基、フラン－２－イル基、チオフェン－２－イル基、ピリジン－２－イル基、又は下記一般式（６）

（式（６）中、Ｒ^３は、水素原子、メチル基、ハロゲン原子、ニトロ基、トリフルオロメチル基、メトキシ基、又はトリフルオロメトキシ基を示す）を示し、Ｒ^２は水素原子、ナフタレン－１－イル基、ナフタレン－２－イル基、フラン－２－イル基、チオフェン－２－イル基、ピリジン－２－イル基、又は下記一般式（７）

（式（７）中、Ｒ^４は、水素原子、メチル基、ハロゲン原子、ニトロ基、トリフルオロメチル基、メトキシ基、又はトリフルオロメトキシ基を示す）、又は下記一般式（８）

（式（８）中、Ｒ^５は、水素原子、メチル基、ハロゲン原子、ニトロ基、トリフルオロメチル基、メトキシ基、又はトリフルオロメトキシ基を示す）を示し、Ｒ^１とＲ^２は結合して環を形成しても良い］
で表される、ペンタフルオロエチル基含有化合物の製造方法。
なお、カルボニル化合物類を、有機溶剤存在下、塩基及びペンタフルオロエタンをマイクロミキサー及びマイクロリアクターに供給かつ混合する際、連絡的に行なってもよいし、一時停止するなど不連続に行なうこともできる。
［２］塩基が、カリウム ｔｅｒｔ－ブトキシド、及び／又はカリウムヘキサメチルジシラジドであることを特徴とする、項［１］に記載のペンタフルオロエチル基含有化合物の製造方法。
［３］有機溶剤が、トルエン、テトラヒドロフラン、及び／又はＮ，Ｎ－ジメチルホルムアミドであることを特徴とする、項［１］又は項［２］に記載のペンタフルオロエチル基含有化合物の製造方法。
［４］反応温度が、－５０℃～４０℃の温度範囲であることを特徴とする項［１］乃至項［３］のいずれかに記載のペンタフルオロエチル基含有化合物の製造方法。
［５］マイクロミキサー内でのカルボニル化合物類、塩基、及びペンタフルオロエタン混合時間が０．００１秒～１秒の範囲であることを特徴とする項［１］乃至項［４］のいずれかに記載のペンタフルオロエチル基含有化合物の製造方法。
［６］３剤同時混合が可能な構造を有しているマイクロミキサーを用いることを特徴とする項［１］乃至項［５］のいずれかに記載のペンタフルオロエチル基含有化合物の製造方法を提供するものである。 That is, the present invention relates to the inventions described below.
[1] General formula (1) below

[In formula (1), R ¹ is naphthalene-1-yl group, naphthalene-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, or the following general formula (2)

(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), R ² represents a hydrogen atom, pyridine- 2-yl group, or the following general formula (3)

(In formula (3), R ⁴ represents a hydrogen atom or a methoxy group), or the following general formula (4)

(in formula (4), R ⁵ represents a hydrogen atom or a methoxy group), and R ¹ and R ² may combine to form a ring]
A carbonyl compound represented by the following general formula (5) is reacted by supplying and mixing a base and pentafluoroethane using a micromixer and a microreactor in the presence of an organic solvent.

[In the formula (5), R ¹ is a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophen-2-yl group, a pyridin-2-yl group, or the following general formula ( 6)

(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), R ² represents a hydrogen atom, naphthalene- 1-yl group, naphthalene-2-yl group, furan-2-yl group, thiophen-2-yl group, pyridin-2-yl group, or the following general formula (7)

(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 the following general formula (8)

(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 are bonded may form a ring]
A method for producing a pentafluoroethyl group-containing compound represented by
In the presence of an organic solvent, the carbonyl compound, the base and the pentafluoroethane may be fed and mixed in the micromixer and the microreactor continuously or discontinuously, such as by temporarily stopping the feeding. .
[2] The method for producing a pentafluoroethyl group-containing compound according to item [1], wherein the base is potassium tert-butoxide and/or potassium hexamethyldisilazide.
[3] The method for producing a pentafluoroethyl group-containing compound according to [1] or [2], wherein 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 items [1] to [3], wherein the reaction temperature is in the range of -50°C to 40°C.
[5] Any one of items [1] to [4], wherein the mixing time of the carbonyl compound, the base, and pentafluoroethane in the micromixer is in the range of 0.001 second to 1 second. A method for producing the described pentafluoroethyl group-containing compound.
[6] The method for producing a pentafluoroethyl group-containing compound according to any one of [1] to [5], wherein a micromixer having a structure capable of simultaneously mixing three agents is used. It provides.

INDUSTRIAL APPLICABILITY According to the present invention, pentafluoroethane is used as a raw material, chemically unstable pentafluoroethyl anions are generated, and pentafluoroethylation to various carbonyl compounds can be carried out under mild conditions.

1 is a diagram showing an example of a microflow reactor embodying the present invention; FIG.

The present invention will be described in detail below.
Apparatuses applicable to the present invention include a metering pump that supplies a predetermined amount of a carbonyl compound solution and a base solution, a mass flow controller that supplies a predetermined amount of trifluoroethane as a gas, a carbonyl compound solution, and a base. It is a continuous reaction apparatus, which consists of a micromixer for mixing a solution and trifluoroethane, and a microreactor for reacting the mixture. In 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 a carbonyl compound are mixed in advance and reacted with trifluoroethane.

Specific examples of compounds represented by the general formula (1) in which R ² is a hydrogen atom applicable to the present invention 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-bromobenzaldehyde, 2- iodobenzaldehyde, 3-iodobenzaldehyde, 4-iodobenzaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 2-(trifluoromethyl)benzaldehyde, 3-(trifluoromethyl)benzaldehyde, 4-(trifluoromethyl)benzaldehyde, fluoromethyl)benzaldehyde, 2-methoxybenzaldehyde, 3-methoxybenzaldehyde, 4-methoxybenzaldehyde, 2-(trifluoromethoxy)benzaldehyde, 3-(trifluoromethoxy)benzaldehyde, 4-(trifluoromethoxy)benzaldehyde, biphenyl-2 -carboxaldehyde, biphenyl-3-carboxaldehyde, and biphenyl-4-carboxaldehyde.

Specific examples of compounds represented by general formula (1) in which R ² is a phenyl group applicable to the present invention include 1-benzoylnaphthalene, 2-benzoylnaphthalene, 2-benzoylfuran, 3-benzoyl furan, 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, 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.

Specific examples of compounds represented by general formula (1) in which R ² is a 2-methoxyphenyl group applicable to the present invention 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, 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, 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.

Specific examples of compounds represented by the general formula (1) in which R ² is a 3-methoxyphenyl group applicable to the present invention 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'-methoxybenzophenone, 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 '-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, 4-biphenyl(3-methoxyphenyl) ketones and the like.

Specific examples of compounds represented by the general formula (1) applicable to the present invention in which R ² 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'-methoxybenzophenone, 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'-methoxybenzophenone, 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, 4-biphenyl(4-methoxyphenyl)ketone and the like.

Specific examples of compounds represented by the general formula (1) applicable to the present invention in which R ² 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, 4- biphenyl-2-pyridyl ketone and the like.

Specific examples of the compound represented by the general formula (1) applicable to the present invention in which R ² is (E)-2-phenylethenyl group include 3-phenyl-1-(naphthalene-1 -yl)-2-propen-1-one, 3-phenyl-1-(naphthalen-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-(thiophen-2-yl)-2-propen-1-one, 3-phenyl-1-(thiophen-3-yl)-2-propen-1-one, 3-phenyl-1-(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, 3-phenyl-1-( 4-fluorophenyl)-2-propen-1-one, 3-phenyl-1-(2-chlorophenyl)-2-propen-1-one, 3-phenyl-1-(3-chlorophenyl)-2-propene- 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-(trifluoromethoxy)phenyl]-2-propen-1-one, 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, 3-phenyl-1-(4-biphenyl)-2-propen-1-one, etc. .

Specific examples of the compound represented by the general formula (1) applicable to the present invention, in which R ² is a (E)-2-(4-fluorophenyl)ethenyl group, include 3-(4-fluoro Phenyl)-1-(naphthalen-1-yl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(naphthalen-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, 3-(4-fluorophenyl)-1-(thiophen-2-yl)-2-propen-1-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-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-propene n-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-(2-methoxyphenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-methoxyphenyl)-2-propene-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.

Specific examples of the compound represented by general formula (1) applicable to the present invention and formed by combining R ¹ and R ² to form a ring include 9-fluorenone, 2-adamantanone, and the like. .

Specific examples of compounds represented by general formula (5) in which R ² is a hydrogen atom applicable to the present invention 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-(thiophen-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(thiophen-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-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-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-iodophyl phenyl)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-penta Fluoro-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]propane -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-pentafluoro-1-[4-(trifluoro Methoxy)phenyl]propan-1-ol, 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, 2,2,3,3,3-pentafluoro-1-[(1,1 '-biphenyl)-4-yl]propan-1-ol and the like.

Specific examples of compounds represented by general formula (5) in which R ² is a phenyl group applicable to the present invention include 2,2,3,3,3-pentafluoro-1-(naphthalene- 1-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalen-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, 2,2,3,3,3-pentafluoro-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-phenyl Propan-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-phenyl Propan-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-1-(3-fluorophenyl)-1-phenylpropan-1-ol, 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-(2-bromo Phenyl)-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-phenylpropane -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, fluoromethyl)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 -phenylpropan-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, 2,2,3,3,3-pentafluoro-1-(1,1′-biphenyl-3-y (l)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1′-biphenyl-4-yl)-1-phenylpropan-1-ol and the like mentioned.

Specific examples of compounds represented by general formula (5) in which R ² is a 2-methoxyphenyl group applicable to the present invention include 2,2,3,3,3-pentafluoro-1- (naphthalen-1-yl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalen-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, 2,2,3,3,3-pentafluoro-1-(thiophene -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-methyl thoxyphenyl)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-bromophenyl)-1-(2-methoxyphenyl)propan-1-ol, 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-nitro Phenyl)-1-(2-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(2-methoxyphenyl)propane-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, 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)propane-1 -ol, 2,2,3,3,3-pentafluoro-1-(2-methoxyphenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro Fluoro-1-(2-methoxyphenyl)-1-(4-methoxyphenyl)propane-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 be done.

Specific examples of compounds represented by general formula (5) in which R ² is a 3-methoxyphenyl group applicable to the present invention include 2,2,3,3,3-pentafluoro-1- (Naphthalen-1-yl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalen-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, 2,2,3,3,3-pentafluoro-1-(thiophene -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-methyl thoxyphenyl)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, 2,2,3,3,3-pentafluoro-1-(3-nitro Phenyl)-1-(3-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(3-methoxyphenyl)propane-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)propan-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)propane-1 -ol, 2,2,3,3,3-pentafluoro-1-(3-methoxyphenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro Fluoro-1-[2-(trifluoromethoxy)phenyl]-1-(3-methoxyphenyl ) propan-1-ol, 2,2,3,3,3-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, 2,2,3,3,3-pentafluoro-1-(1,1′-biphenyl-4-yl)-1 -(3-methoxyphenyl)propan-1-ol and the like.

Specific examples of compounds represented by the general formula (5) in which R ² is a 4-methoxyphenyl group applicable to the present invention include 2,2,3,3,3-pentafluoro-1- (Naphthalen-1-yl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalen-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, 2,2,3,3,3-pentafluoro-1-(thiophene -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-methyl thoxyphenyl)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-(2-nitrophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-nitro Phenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-nitrophenyl)-1-(4-methoxyphenyl)propane-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)propane-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, 2,2,3,3,3-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, 2,2,3,3,3-pentafluoro-1-(1 , 1′-biphenyl-4-yl)-1-(4-methoxyphenyl)propan-1-ol and the like.

Specific examples of compounds represented by the general formula (5) in which R ² is a pyridin-2-yl group applicable to the present invention include 2,2,3,3,3-pentafluoro-1 -(naphthalen-1-yl)-1-(pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(naphthalen-2-yl)-1-( Pyridin-2-yl)propan-1-ol, 2,2,3,3,3-pentafluoro-1,1-bis(pyridin-2-yl)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)propane-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-(trifluoromethyl)phenyl]-1-(pyridin-2-yl)propane -1-ol, 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.

Specific examples of compounds represented by the general formula (5) applicable to the present invention in which R ² is a (E)-2-phenylethenyl group include (E)-4,4,5, 5,5-pentafluoro-3-(naphthalen-1-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-( Naphthalen-2-yl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(furan-2-yl)-1-phenyl pent-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-phenyl pent-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-phenyl Pent-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)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(2-iodo Phenyl)-1-phenylpent-1-en-3-ol, (E)-4,4,5,5,5-pentafluoro-3-(3-iodophenyl)-1-phenylpent-1-ene -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, (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-ene- 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-ene- 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.

Specific examples of compounds represented by general formula (5) applicable to the present invention, wherein R ² is (E)-2-(4-fluorophenyl)ethenyl group, include (E)-4, 4,5,5,5-pentafluoro-3-(naphthalen-1-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, (E)-4,4,5,5 ,5-pentafluoro-3-(naphthalen-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-ene- 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)-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-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-pen Tafluoro-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-ene-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-1-en-3-ol, (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-ene- 3-ol, (E)-4,4,5,5,5-pentafluoro-3-[2-(trifluoromethyl)phenyl]-1-(4-fluorophenyl)pent-1-ene-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-[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-ene -3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1′-biphenyl-2-yl)-1-(4-fluorophenyl)pent-1-ene -3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1′-biphenyl-3-yl)-1-(4-fluorophenyl)pent-1-ene -3-ol, (E)-4,4,5,5,5-pentafluoro-3-(1,1′-biphenyl-4-yl)-1-(4-fluorophenyl)pent-1-ene -3-ol and the like.

Specific examples of the compound represented by general formula (5) applicable to the present invention and formed by combining R ¹ and R ² to form a ring include 9-(perfluoroethyl)-9H-fluorene- 9-ol, 2-(pentafluoroethyl)-2-adamantanol and the like.

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, sodium diisopropylamide and the like can be mentioned, but potassium hexamethyldisilazide and potassium tert-butoxide are preferred from the viewpoint of reactivity, and the amount used is determined by the amount of the carbonyl compound used in the reaction. It is preferable to use 1.1 mol to 3.0 mol per 1 mol of the compound.

The amount of trifluoroethane used in the present invention is theoretically 1.0 mol or more per 1.0 mol of the carbonyl compound used in the reaction. A 10.0 molar amount should be used.

Solvents applicable to the present invention are not particularly limited as long as they are inert to the reaction, but specific examples include diisopropyl ether, methyl tert-butyl ether, methylcyclopentyl ether, and tetrahydrofuran (hereinafter abbreviated as THF). Ether-based solvents such as toluene, ethylbenzene, xylene and other aromatic hydrocarbon-based solvents, N,N-dimethylformamide (hereinafter abbreviated as DMF), N,N-dimethylacetamide, N-methylpyrrolidine and other aprotic polar solvents Preferably, THF, DMF, and toluene may be used alone or in combination, and the amount of the carbonyl compounds and base used in the reaction is determined by It is preferable to use 5 to 50 times the weight of the product.

The reaction temperature applicable to the present invention varies depending on the type of carbonyl compound used in the reaction, the type of base used, and the type of solvent used, but is usually in the 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 0. It ranges from 0.001 second to 1.0 second. Based on the volume of the mixing section of the micromixer and the total volume of the feed per unit time, it is preferable to carry out the reaction at a feed rate that gives a mixing time of 1.0 second or less.
The reaction time after mixing the carbonyl compound of the present invention, the base and trifluoroethane can be defined by the inner diameter and length of the microreactor (device for chemical reaction in a microspace), and is usually within 10 seconds. .
In the present invention, the micromixer and microreactor used for the reaction may be those commonly available and commercially available, or those that are suitably designed for the present invention. In addition, the micromixer and microreactor may be accompanied by a heating or cooling device as necessary, and additional equipment for accelerating the reaction may be added as appropriate.
Post-treatment after the reaction of the present invention can be carried out by a well-known method. For example, after neutralization with a saturated aqueous solution of ammonium chloride, extraction with an organic solvent such as diethyl ether, drying with a drying agent such as sodium sulfate, and filtration. Alternatively, the desired product may be obtained as a crude product by concentration, and further purified by silica gel column chromatography or the like to obtain the purified desired product.

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

The following instruments were used for analysis.
¹ H-NMR (300 MHz), ¹⁹ F-NMR (282 MHz), ¹³ C-NMR (125.8 MHz): Burker Avance 500US, Varian Mercury 300.
HRMS: Shimadzu GCMS-QP5050A (SHIMADZU GCMS-QP5050A).
ESI-MS: Shimadzu LCMS-2010EV (SHIMADZU LCMS-2010EV).
IR: FT/IR-4100 manufactured by Jusco (JASCO FT/IR-4100).
Melting point: BUCHI Labortehnik AG-565 from Wuchi.

For the reaction, a microflow reactor shown in FIG. 1 was used.
In FIG. 1, A is a mass flow controller (Flow Reactor FFX-1000G manufactured by Tokyo Rikakikai Co., Ltd. (using only the gas flow rate control function)).
B-1 and B-2 are syringe pumps (YMC syringe pump YSP-101) equipped with 5 mL gas-tight syringes.
C is a micromixer (4-way micro swirl mixer manufactured by Sugiyama Shoji Co., Ltd.), made of SUS316, having an inner diameter of 0.8 mm, a length of 12 mm, and a volume of 60 μL.
D is a microreactor, D-1 is made of SUS316, has an inner diameter of 0.8 mm and a length of 640 mm. D-2 is made of SUS316, has an inner diameter of 0.8 mm and a length of 1612 mm. A volume of 0.81 mL was used.

Each part was connected with a joint of 1/16 inch.
For the CF ₃ CF ₂ H supply line shown in FIG. 1, a SUS316 pipe with an inner diameter of 0.8 mm was used.
A supply line for a solution of KHMDS and tBuOK shown as "(KHMDS or tBuOK) in solvent" in FIG. 1 and a carbonyl compound having substituents R ¹ and R ² shown as "1,3,5 in solvent" in FIG. A PTFE pipe with an inner diameter of 0.8 mm was used as a supply line for the solution of . The supply line for the KHMDS or tBuOK solution and the supply line for the carbonyl compound solution may be supplied separately or may be supplied together. When using a mixture of KHMDS and tBuOK, KHMDS and tBuOK may be mixed in advance, or a mixer capable of mixing the two liquids and another syringe pump may be added before the micromixer. , may be supplied separately.

４－ブロモベンズアルデヒド（１ａ）（２２２ｍｇ，１．２０ｍｍｏｌ）を無水ＤＭＦ（２．０ｍＬ）に溶解させた４－ブロモベンズアルデヒド溶液（０．６０Ｍ）を５ｍＬのガスタイトシリンジに入れ、シリンジポンプ（Ｂ－１）に装着した。同様にカリウムｔｅｒｔ－ブトキシド（２６９ｍｇ，２．４０ｍｍｏｌ）をＤＭＦ（４ｍｌ）に溶解させたカリウムｔｅｒｔ－ブトキシド溶液（０．６０Ｍ）を別のガスタイトシリンジに入れ、シリンジポンプ（Ｂ－２）に装着した。
４－ブロモベンズアルデヒド溶液を０．３３ｍＬ／ｍｉｎ及びカリウムｔｅｒｔ－ブトキシド溶液を０．５０ｍＬを、予め恒温槽を用い－１０℃に冷却したミキサーＣ及びマイクロリアクターＤ（Ｄ－１を使用）に供給しながら、これにペンタフルオロエタン（０．１ＭＰａ）を１５ｍＬ／ｍｉｎで供給（ペンタフルオロエタン／４－ブロモベンズアルデヒド＝３．１０／１ ｍｏｌ／ｍｏｌ）、ペンタフルオロエタンの供給が安定した時点で、１分間、マイクロリアクター（Ｄ）の出口からの留出物を、飽和塩化アンモニウム水溶液でクエンチした。次いで、エチルエーテルで抽出、得られた有機層を飽和食塩水で洗浄、硫酸ナトリウム上で乾燥、ろ過、減圧下濃縮し、目的物の粗製物を得た。
なお、安定反応時における、マイクロミキサーでの混合時間は０．２２秒、マイクロリアクターでの反応時間は３．１秒であった。 Example 1 Preparation of 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a)

4-bromobenzaldehyde (1a) (222 mg, 1.20 mmol) was dissolved in anhydrous DMF (2.0 mL). A 4-bromobenzaldehyde solution (0.60 M) was placed in a 5 mL gas-tight syringe, and the syringe pump (B- 1) was installed. Similarly, a potassium tert-butoxide solution (0.60 M) obtained by dissolving potassium tert-butoxide (269 mg, 2.40 mmol) in DMF (4 ml) was put into another gas-tight syringe and attached to the syringe pump (B-2). did.
0.33 mL/min of 4-bromobenzaldehyde solution and 0.50 mL of potassium tert-butoxide solution were supplied to mixer C and microreactor D (using D-1) previously cooled to −10° C. using a constant temperature bath. Meanwhile, pentafluoroethane (0.1 MPa) was supplied at 15 mL/min (pentafluoroethane/4-bromobenzaldehyde = 3.10/1 mol/mol). Minutes, the distillate from the outlet of the microreactor (D) was quenched with saturated aqueous ammonium chloride solution. Then, it was extracted with ethyl ether, and the resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product of the desired product.
The mixing time in the micromixer and the reaction time in the microreactor during the stable reaction were 0.22 seconds and 3.1 seconds, respectively.

The obtained crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard substance, and the desired product, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propane- The yield of 1-ol (2a) was 92%.
The resulting crude product was purified by silica gel column chromatography (hexane/dichloromethane = 1/1 vol/vol) to obtain the desired product, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl ) gave propan-1-ol (2a) (54.4 mg, 0.178 mmol, 90% yield) as a white solid.

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

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

Example 9 Preparation of 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) Using the same reactor as in Example 1, 4-bromobenzaldehyde solution ( 0.60 M) was replaced with 4-bromobenzaldehyde solution (0.90 M), 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 supplied at 20.0 mL/min, and the reaction was carried out at -10. The obtained crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard substance, and the desired product, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propane- The yield of 1-ol (2a) was 89%.

Examples 10 to 21 Reaction of various aldehydes Using the same reaction apparatus as in Example 1, the microreactor was changed from D-1 to D-2, and the 4-bromobenzaldehyde solution (0.60 M) in Table 2 was used. The same reaction procedure as in Example 1 was carried out, except that a solution (0.60 M) of various aldehydes shown in 1. was used. Table 2 shows the results.

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 desired product as a colorless transparent liquid (40.3 mg, 0.178 mmol, yield 90%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.45 (brs, 5H), 5.18-5.09 (m, 1H), 2.44 (d, J=4.4Hz, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.3 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F ), −129.9 (dd, ² J _FF , ³ J FF =275.9, 17.2 Hz, 1 _F ) 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 desired product as a white solid (46.2 mg, 0.180 mmol, yield 91%).
¹ H NMR (300 MHz, CDCl ₃ ) δ: 7.36 (d, J = 8.8 Hz, 2H), 6.92 (d-lile, J = 8.8 Hz, 2H), 5.08-4.99 (m, 1H), 3.81 (s, 3H), 2.75 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.7 (dd, ² J _FF , ³ J _FF = 274.1, 8.6 Hz, 1 F ), −129.9 (dd, ² J _FF , ³ J FF =275.0, 16.4 Hz, 1 _F ) 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 desired product as a white solid (52.7 mg, 0.174 mmol, yield 88%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.67-7.37 (m, 9H), 5.23-5.14 (m, 1H), 2.56 (d, J = 4.1Hz, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.2 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F ), −130.0 (dd, ² J _FF , ³ J FF =275.9, 17.2 Hz, 1 _F ) 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 desired product as a white solid (46.5 mg, 0.178 mmol, yield 90%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.41 (brs, 4H), 5.18-5.08 (m, 1H), 2.47 (d, J=4.1Hz, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.3 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F ), −129.8 (dd, ² J _FF , ³ J FF =275.9, 15.5 Hz, 1 _F ) 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 desired product as a white solid (64.0 mg, 0.182 mmol, yield 92%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.76 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.2 Hz, 2H), 5.14-5.05 ( m, 1H), 2.52-2.49 (m, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.2 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F ), −129.9 (dd, ² J _FF , ³ J FF =275.9, 15.5 Hz, 1 _F ) ppm.
MS (ESI, m/z) 352 [M+H] ^<+ >.
⁶⁾ 2,2,3,3,3-pentafluoro-1-(4-fluorophenyl)propan-1-ol (2 g)
The crude product was purified by silica gel column chromatography (hexane/dichloromethane=1/1 vol/vol) to obtain the desired product as a colorless transparent liquid (42.1 mg, 0.172 mmol, yield 87%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.46 (t-lile, J = 6.5 Hz, 2H), 7.12 (t-like, J = 8.5 Hz, 2H), 5.18- 5.09 (m, 1 H), 2.45 (d, J = 4.4 Hz, 1 H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.6 (s, 3F), −111.9 (s, 1F), −122.5 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F), -129.7 (dd, ² J _FF , ³ J FF = 275.9, 15.5 Hz, 1 _F ) 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 desired product as a colorless transparent liquid (52.8 mg, 0.170 mmol, yield 86%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.52 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 5.21-5.12 ( m, 1 H), 2.60 (d, J=4.4 Hz, 1 H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −58.3 (s, 3F), −81.6 (s, 3F), −122.2 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F), -129.9 (dd, ² J _FF , ³ J _FF = 276.7, 16.4 Hz, 1 F) 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 desired product as a white solid (49.8 mg, 0.180 mmol, yield 91%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.95-7.87 (m, 4H), 7.59-7.53 (m, 3H), 5.36-5.26 (m, 1H) , 2.58 (d, J=4.7 Hz, 1 H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.7 (s, 3F), −122.1 (dd, ² J _FF , ³ J _FF = 275.9, 6.9 Hz, 1 F ), −129.6 (dd, ² J _FF , ³ J FF =275.9, 15.5 Hz, 1 _F ) 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 desired product as a yellow solid (44.8 mg, 0.162 mmol, yield 82%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 8.02 (d, J=7.6 Hz, 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 (282 MHz, CDCl ₃ ) δ: −81.8 (s, 3F), −122.1 (dd, ² J _FF , ³ J _FF = 274.1, 6.9 Hz, 1 F ), −130.5 (dd, ² J _FF , ³ J FF =274.1, 17.2 Hz, 1 _F ) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ) 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, 34.4 Hz), 116.0-111.0 (m), 67.7 (dd, ² J _{C- Fa} , ² J _{C - Fb} = 29.1, 21.8 Hz) ppm.
ATR-FTIR (KBr): n=3465, 3059, 1514, 1351, 1185, 1134, 1080, 1026, 790, 720 cm ⁻¹ .
HRMS (ESI) m/z: [M−H] ⁻ calcd. for _C13H8F5O ; _275.0495 , found: _275.0497 .
Melting point: 45.5-46.3°C.
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 desired product as a yellow liquid (27.8 mg, 0.129 mmol, yield 65%).
¹ H-NMR (300MHZ, CDCl ₃ ) δ: 7.49 (s, 1H), 6.54 (s, 1H), 6.44 (s, 1H), 5.20-5.10 (m, 1H) ), 2.59 (d, J=7.9 Hz, 1 H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −82.4 (s, 3F), −123.2 (dd, ² J _FF , ³ J _FF = 274.1, 6.9 Hz, 1 F ), −129.3 (dd, ² J _FF , ³ J FF =275.0, 16.4 Hz, 1 _F ) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ) δ: 146.8, 144.0, 118.94 (qt, ¹ J _CF , ² J _CF = 286.6, 35.2 Hz), 115.1 −110.1 (m), 111.0, 110.8, 66.5 (q, ² J _C−F =17.3 Hz) ppm.
ATR-FTIR (KBr): n=3407, 2927, 1507, 1363, 1192, 1138, 1015, 929, 809, 744 cm ⁻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 desired product as a yellow liquid (31.7 mg, 0.137 mmol, yield 69%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.43 (d, J=4.4 Hz, 1H), 7.21 (brs, 1H), 7.08-7.05 (m, 1H), 5 .39 (dd, J=16.5, 5.9 Hz, 1H), 2.69 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −81.8 (s, 3F), −122.1 (dd, ² J _FF , ³ J _FF = 274.1, 6.9 Hz, 1 F ), −130.5 (dd, ² J _FF , ³ J FF =274.1, 17.2 Hz, 1 _F ) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ) δ: 136.0, 128.2, 127.7, 127.1, 119.1 (qt, ¹ J _CF , ² J _CF = 287.0, 35.4 Hz), 115.1-110.1 (m), 68.5 (q, ² J _{C -F} = 17.6 Hz) ppm.
ATR-FTIR (neat): n=3426, 2923, 1432, 1355, 1208, 1131, 1023, 809, 708 cm ⁻¹ .
HRMS (ESI) m/z: [M−H] ⁻ calcd. for _{C7H4F5OS ; 230.9903} , found: 230.9911.

ベンゾフェノン（３ａ）（２１９ｍｇ，１．２０ｍｍｏｌ）を無水ＤＭＦ（２．０ｍＬ）に溶解させたベンゾフェノン溶液（０．６０Ｍ）を５ｍＬのガスタイトシリンジに入れ、シリンジポンプ（Ｂ－１）に装着した。同様にカリウムｔｅｒｔ－ブトキシド（２６９ｍｇ，２．４０ｍｍｏｌ）をＤＭＦ（４ｍｌ）に溶解させたカリウムｔｅｒｔ－ブトキシド溶液（０．６０Ｍ）を別のガスタイトシリンジに入れ、シリンジポンプ（Ｂ－２）に装着した。 Example 21 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a)

A benzophenone solution (0.60 M) prepared by dissolving benzophenone (3a) (219 mg, 1.20 mmol) in anhydrous DMF (2.0 mL) was placed in a 5 mL gas-tight syringe, which was attached to a syringe pump (B-1). Similarly, a potassium tert-butoxide solution (0.60 M) obtained by dissolving potassium tert-butoxide (269 mg, 2.40 mmol) in DMF (4 ml) was put into another gas-tight syringe and attached to the syringe pump (B-2). did.

0.30 mL/min of acetophenone solution and 0.60 mL of potassium tert-butoxide solution are supplied to mixer C and microreactor D (using D-1) at room temperature while pentafluoroethane (0.1 MPa) is added thereto. was supplied at 15 mL/min (pentafluoroethane/benzophenone = 3.41/1 mol/mol), and when the pentafluoroethane supply was stabilized, the distillate from the outlet of the microreactor D-1 was fed for 1 minute. was quenched with saturated aqueous ammonium chloride. Then, it was extracted with ethyl ether, and the resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product of the desired product.
The mixing time in the micromixer and the reaction time in the microreactor during the stable reaction were 0.23 seconds and 1.2 seconds, respectively.

The obtained crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard substance, and the desired product, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol The yield of (4a) was 94%.
The resulting crude product was purified by silica gel column chromatography (hexane/dichloromethane = 1/1 vol/vol) to give the desired product 2,2,3,3,3-pentafluoro-1,1-diphenylpropane- 1-ol (4a) (50.0 mg, 0.166 mmol, 92% yield) was obtained as a white solid.

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

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

Example 29 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) Using the same reactor as in Example 21, a benzophenone solution (0.60 M) was solution (0.90 M), supply at 0.33 mL/min, supply potassium tert-butoxide solution (0.60 M) at 0.66 mL/min, and pentafluoroethane (0.1 MPa) at 25.0 mL/ min and the reaction was carried out at room temperature. The obtained crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard substance, and the desired product, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol The yield of (4a) was 91%.

Example 30 Preparation of 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) Using the same reactor as in Example 21, a benzophenone solution (0.60 M) was 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) at 25.0 mL/ min and the reaction was carried out at room temperature. The obtained crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard substance, and the desired product, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol The yield of (4a) was 73%.

Examples 31 to 41 Reactions of various ketones Using the same reaction apparatus as in Example 21, except that the benzophenone solution (0.60 M) was replaced with the solutions of various aldehydes (0.60 M) shown in Table 4. , the same reaction procedure as in Example 21 was performed. Table 4 shows the results.

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 desired product as a colorless transparent liquid (49.1 mg, 0.155 mmol, yield 86%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.55 (d, J = 6.8 Hz, 2H), 7.43 (d, J = 7.6 Hz, 2H), 7.35-7.33 ( m, 3H), 7.15 (d, J=7.9 Hz, 2H), 2.81 (s, 1H), 2.34 (s, 3H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) 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 desired product as a colorless transparent liquid (60.8 mg, 0.167 mmol, yield 93%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.45 (d, J = 8.8 Hz, 4H), 6.85 (d, J = 8.8 Hz, 4H), 3.79 (s, 6H) , 2.89(s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) 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 desired product as a colorless transparent liquid (51.7 mg, 0.153 mmol, yield 85%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.99 (d, J=7.1 Hz, 1H), 7.43-7.35 (m, 8H), 4.03 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −76.7 (s, 3F), −114.0 (d, ² J _FF =275.9 Hz, 1F), −116.6 (d, ² J FF =275.9 Hz, 1 _F ) ppm.
¹³ C-NMR (126 MHz, CDCl ₃ ) δ: 138.1, 137.2, 133.3, 132.6, 130.1, 129.1 (t, ³ J _CF = 5.9 Hz), 128 .7, 128.0, 127.9, 126.6, 119.3 (qt, ¹ JCF = _288.4 , 35.0 Hz), 117.7-112.6 (m), 80.6 ( _t , ² JCF = 23.2 Hz) ppm.
ATR-FTIR (neat): n=3555, 3067, 1452, 1336, 1223, 1134, 1050, 910, 863, 755 cm ⁻¹ .
HRMS (ESI) m/z: [M−H] ⁻ calcd. for _C15H9CLF5O ; _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 desired product as a colorless transparent liquid (52.7 mg, 0.157 mmol, yield 87%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.63 (s, 1H), 7.59-7.56 (m, 2H), 7.46 (d, J = 7.1 Hz, 1H), 7 .39-7.29 (m, 5H), 2.97 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −77.6 (s, 3F), −116.4 (d, ² J _FF =279.3 Hz, 1F), −117.6 (d, ² J FF =279.3 Hz, 1 _F ) 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 desired product as a colorless transparent liquid (56.3 mg, 0.167 mmol, yield 93%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.56-7.52 (m, 4H), 7.38-7.32 (m, 5H), 2.92 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −77.6 (s, 3F), −116.5 (d, ² J _FF =279.3 Hz, 1F), −117.7 (d, ² J FF =277.6 Hz, 1 _F ) ppm.
MS (ESI, m/e) 335 [MH] ⁻ .
⁶⁾ 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)-1-phenylpropan-1-ol (4 g)
The crude product was purified by silica gel column chromatography (hexane/dichloromethane=1/1 vol/vol) to obtain the desired product as a colorless transparent liquid (62.4 mg, 0.164 mmol, yield 91%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.53-7.35 (m, 9H), 2.90 (d-like, J=6.5Hz, 1H) ppm.
¹⁹ F-NMR (282 MHZ, CDCl ₃ ) δ: −77.5 (s, 3F), −116.4 (d, ² J _FF =277.6 Hz, 1F), −117.6 (d, ² J FF =277.6 Hz, 1 _F ) 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 desired product as a yellow solid (47.6 mg, 0.134 mmol, yield 76%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 8.18 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.54-7.52 ( m, 2H), 7.39-7.37 (m, 3H), 3.16 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −77.5 (s, 3F), −115.9 (d, ² J _FF =279.3 Hz, 1F), −118.0 (d, ² J FF =279.3 Hz, 1 _F ) 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 desired product as a colorless transparent liquid (58.1 mg, 0.157 mmol, yield 87%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.70 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 7.56-7.53 ( M, 2H), 7.41-7.33 (m, 3H), 2.99 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −63.3 (s, 3F), −77.5 (s, 3F), −116.3 (d, ² J FF = 279.3 Hz, 1 _F ), −117.8 (d, ² J FF =277.6 Hz, 1 _F ) 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 desired product as a white solid (48.7 mg, 0.162 mmol, yield 90%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.73-7.63 (m, 4H), 7.48 (t-like, J = 7.4 Hz, 2H), 7.35 (t-lile, J=7.5 Hz, 2H), 2.78 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) 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 desired product as a white solid (46.4 mg, 0.153 mmol, yield 85%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 8.60-8.58 (m, 2H), 8.24 (d-like, J = 7.9 Hz, 2H), 7.79-7.73 ( m, 2H), 7.58 (s, 1H), 7.31-7.26 (m, 2H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −78.5 (s, 3F), −118.3 (s, 2F) ppm.
MS (ESI, m/z) 305 [M+Na] ^<+ >.
¹¹⁾ 2-(pentafluoroethyl)-2-adamantanol (4 l)
The crude product was purified by silica gel column chromatography (hexane/diethyl ether=4/1 vol/vol) to obtain the desired product as a white solid (41.4 mg, 0.153 mmol, yield 85%).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 2.27-2.12 (m, 6H), 1.92-1.75 (m, 7H), 1.61 (d, J = 12.4 Hz, 2H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −78.6 (s, 3F), −117.4 (s, 2F) ppm.
MS (ESI, m/z) 269 [MH] ⁻ .

実施例２１と同じマイクロフロー反応装置を用い、カルコン（５ａ）（１２５ｍｇ，０．６０ｍｍｏｌ）を無水トルエン（２．０ｍＬ）に溶解させたカルコン溶液（０．３Ｍ）を５ｍＬのガスタイトシリンジに入れ、シリンジポンプ（Ｂ－１）に装着した。同様にＫＨＭＤＳ（２３９ｍｇ，１．２０ｍｍｏｌ）をトルエン（４．０ｍＬ）に溶解させたＫＨＭＤＳ溶液（０．３Ｍ）を別のガスタイトシリンジに入れ、シリンジポンプ（Ｂ－２）に装着した。 Example 42 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a)

Using the same microflow reactor as in Example 21, chalcone (5a) (125 mg, 0.60 mmol) was dissolved in anhydrous toluene (2.0 mL), and a chalcone solution (0.3 M) was put into a 5 mL gas-tight syringe. , and attached to the 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 the syringe pump (B-2).

While supplying the chalcone solution at a rate of 0.33 mL/min and the KHMDS solution at a rate of 0.50 mL/min at room temperature to mixer C and microreactor D (using D-1), pentafluoroethane (0. 1 MPa) was supplied at 7.5 mL/min (pentafluoroethane/chalcone = 3.10/1 mol/mol), and when the supply of pentafluoroethane was stabilized, the The distillate was quenched with saturated aqueous ammonium chloride. Then, it was extracted with ethyl ether, and the resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude target product.
The mixing time in the micromixer and the reaction time in the microreactor during the stable reaction were 0.43 seconds and 2.3 seconds, respectively.

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

The analysis results are shown below.
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.65 (d, J=7.1 Hz, 2H), 7.44-7.29 (m, 8H), 6.86 (brs, 2H), 2 .74 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −78.2 (s, 3F), −121.0 (d, ² J _FF =279.3 Hz, 1F), −122.0 (d, ² J FF =277.6 Hz, 1 _F ) ppm.
MS (ESI, m/z) 327 [MH] ⁻ .

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

Example 46
Using the same reaction apparatus as in Example 42, the same operation as in Example 43 was performed except that the reaction temperature in Example 43 was changed from room temperature to −10° C., and the desired product (E)-4, 4, 5, 5 ,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) was obtained with 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 KHMDS concentration was changed to 0.6 M and the feed rate was changed to 0.30 mL/min, the chalcone solution (0.30 M) was fed at 0.30 mL/min, and the pentafluoroethane (0.1 MPa) feed rate was 25 mL/min. , and the reaction was carried out in the same manner except that the solvent species was changed. The results are shown in Table 6.

Example 50 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) The same procedure as in Example 47 was performed except that tBuOK (0.6M) was used instead of the solution (0.6M) to give the desired product (E)-4,4,5,5,5-pentafluoro-1. ,3-diphenylpent-1-en-3-ol (6a) was obtained in 45% yield.
Examples 51 to 55 Reaction of Various Chalcones Using the microflow reaction apparatus of Example 42, the same operation as in Example 42 was performed except that the chalcone compounds shown in Table 7 were changed to obtain the target product. In addition, Example 55 implemented reaction by the THF solvent. The results are shown in Table 7.

¹⁾ (E)-4,4,5,5,5-pentafluoro-3-(4-methoxyphenyl)-1-phenylpent-1-en-3-ol (6b)
The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate = 9/1 vol/vol) to obtain the desired product as a white solid (31.1 mg, 0.0871 mmol, yield 88%). ).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.55 (d, J=9.1 Hz, 2H), 7.44-7.29 (m, 5H), 6.93 (d, J=9. 1 Hz, 2H), 6.84 (brs, 2H), 3.82 (s, 3H), 2.69 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −78.2 (s, 3F), −121.1 (d, ² J _FF =277.6 Hz, 1F), −122.1 (d, ² J FF =277.6 Hz, 1 _F ) 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 resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate = 9/1 vol/vol) to obtain the desired product as a white solid (31.3 mg, 0.0861 mmol, yield 87%). ).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.58 (d, J=8.5 Hz, 2H), 7.43-7.28 (m, 7H), 6.82 (brs, 2H), 2 .84-2.81 (m, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) 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 desired product as a colorless transparent liquid (35.1 mg, 0.0861 mmol, yield 87 %).
¹ H-NMR (300 MHz, CDCl ₃ ) 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 (282 MHz, CDCl ₃ ) 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 desired product as a yellow liquid (25.2 mg, 0.0693 mmol, yield 70%). ).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 7.61 (dd, J=8.8, 5.3 Hz, 2H), 7.41-7.36 (m, 2H), 7.12-7. 01 (m, 4H), 6.80 (d, J=15.9 Hz, 1 H), 6.73 (d, J=16.2 Hz, 1 H), 2.71 (s, 1 H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) 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 resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate = 9/1 vol/vol) to obtain the desired product as a yellow solid (26.2 mg, 0.0713 mmol, yield 72%). ).
¹ H-NMR (300 MHz, CDCl ₃ ) δ: 8.26 (d, J = 9.1 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.43-7.30 ( m, 5H), 6.89-6.78 (m, 2H), 2.89 (s, 1H) ppm.
¹⁹ F-NMR (282 MHz, CDCl ₃ ) δ: −78.1 (s, 3F), −120.9 (d, ² J _FF =279.3 Hz, 1F), −122.1 (d, ² J FF =279.3 Hz, 1 _F ) ppm.
MS (ESI, m/z) 372 [MH] ⁻ .

The pentafluoroethyl group-containing compound obtained by the method of the present invention is useful as a production intermediate in the fields of pharmaceuticals, agricultural chemicals, and electronic materials.

A: mass flow controller B-1, B-2: syringe pump C: micromixer D: microreactor

Claims (6)

General formula (1) below

[In formula (1), R ¹ is naphthalene-1-yl group, naphthalene-2-yl group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, or the following general formula (2)

(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), R ² represents a hydrogen atom, pyridine- 2-yl group, or the following general formula (3)

(In formula (3), R ⁴ represents a hydrogen atom or a methoxy group), or the following general formula (4)

(in formula (4), R ⁵ represents a hydrogen atom or a methoxy group), and R ¹ and R ² may combine to form a ring]
A carbonyl compound represented by the following general formula (5) is reacted by supplying and mixing a base and pentafluoroethane using a micromixer and a microreactor in the presence of an organic solvent.

[In the formula (5), R ¹ is a naphthalene-1-yl group, a naphthalene-2-yl group, a furan-2-yl group, a thiophen-2-yl group, a pyridin-2-yl group, or the following general formula ( 6)

(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), R ² represents a hydrogen atom, naphthalene- 1-yl group, naphthalene-2-yl group, furan-2-yl group, thiophen-2-yl group, pyridin-2-yl group, or the following general formula (7)

(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 the following general formula (8)

(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 are bonded may form a ring]
A method for producing a pentafluoroethyl group-containing compound represented by 2. The method for producing a pentafluoroethyl group-containing compound according to claim 1, wherein the base is potassium tert-butoxide and/or potassium hexamethyldisilazide. 3. 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. 4. The method for producing a pentafluoroethyl group-containing compound according to any one of claims 1 to 3, wherein the reaction temperature is in the range of -50°C to 40°C. 5. The penta of any one of claims 1 to 4, wherein the mixing time of the carbonyl compound, the base, and pentafluoroethane in the micromixer is in the range of 0.001 second to 1 second. A method for producing a fluoroethyl group-containing compound. 6. The method for producing a pentafluoroethyl group-containing compound according to any one of claims 1 to 5, wherein a micromixer having a structure capable of simultaneously mixing three agents is used.

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