JP7623205B2 - Method for producing a compound containing a pentafluoroethyl group - Google Patents

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

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

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.

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

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 reacted with a carbonyl compound to obtain a trifluoroethyl group-containing compound.

The inventors of the present invention have conducted extensive research into methods for obtaining carbonyl compounds using pentafluoroethane as a raw material, and have discovered that the desired trifluoroethyl group-containing compound can be obtained by instantaneously mixing pentafluoroethane, a base, and a carbonyl compound in a short time of 1.0 second or less using a micromixer and a microreactor in the temperature range of -50°C to 40°C, thus 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] The following general formula (1)

[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):

(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):

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

(In formula (4), ^R5 represents a hydrogen atom or a methoxy group, and ^R1 and ^R2 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:

[In the 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):

(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):

(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), ^R5 represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group), and ^R1 and ^R2 may be bonded to form a ring.)
A method for producing a pentafluoroethyl group-containing compound represented by the 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], characterized in that 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 items [1] to [5], characterized in that a micromixer having a structure capable of simultaneously mixing three components is used.

The present invention makes it possible to generate chemically unstable pentafluoroethyl anions using pentafluoroethane as a raw material, and to perform pentafluoroethylation of various carbonyl compounds under mild conditions.

FIG. 1 is a diagram showing an example of a microflow reactor in which the present invention is implemented.

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 for supplying a predetermined amount of a solution of carbonyl compounds and a solution of a base, a mass flow controller for supplying a predetermined amount of trifluoroethane as a gas, a micromixer for mixing the solution of carbonyl compounds, the solution of a base, and trifluoroethane, and a microreactor for reacting the mixture, and that continuously supplies a predetermined amount of each reagent to carry out the reaction. 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 carbonyl compounds are mixed in advance and reacted with trifluoroethane.

Specific examples of the compound represented by the general formula (1) applicable to the present invention, in which R ² 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-bromobenzaldehyde, 5-bromobenzaldehyde, 6-bromobenzaldehyde, 7-bromobenzaldehyde, 8-bromobenzaldehyde, 9-bromobenzaldehyde, 10-bromobenzaldehyde, 11-bromobenzaldehyde, 12-bromobenzaldehyde, 13-bromobenzaldehyde, 14-bromobenzaldehyde, 15-bromobenzaldehyde, 16-bromobenzaldehyde, 17-bromobenzaldehyde, 18-bromobenzaldehyde, 19-bromobenzaldehyde, 20-bromobenzaldehyde, 21-bromobenzaldehyde, 22-bromobenzaldehyde, 23-bromobenzaldehyde, 24-bromobenzaldehyde, 25-bromobenzaldehyde, 26-bromobenzaldehyde, 27-bromobenzaldehyde, 28-bromobenzaldehyde, 29-bromobenzaldehyde, 30-bromobenzaldehyde, 31-bromobenzaldehyde, 32-bromobenzaldehyde, 33-bromobenzaldehyde, 34-bromo Examples of the benzaldehyde include 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, and biphenyl-4-carboxaldehyde.

Specific examples of the compound represented by general formula (1) applicable to the present invention and in which R ² 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, benzophenone, 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 the compound represented by the general formula (1) applicable to the present invention, in which R ² 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, non, 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 benzophenone, 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 benzophenone, 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 the compound represented by the general formula (1) applicable to the present invention, in which R ² 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'-methoxybenzoyl 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 '-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)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 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, 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 the compound represented by 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, and 4-biphenyl-2-pyridyl ketone.

Represented by general formula (1) applicable to the present invention, R Specific examples of compounds in which ² is an (E)-2-phenylethenyl group include 3-phenyl-1-(naphthalene-1-yl)-2-propene-1-one, 3-phenyl-1-(naphthalene-2-yl)-2-propene-1-one, 3-phenyl-1-(furan-2-yl)-2-propene-1-one, 3-phenyl-1-(furan-3-yl)-2-propene-1-one, 3-phenyl-1-(thiophene-2-yl)-2-propene-1-one, 3-phenyl-1-(thiophene-3-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-2-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-3-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-4-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-5-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-6-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-7-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-8-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-9-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-10-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-11-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-12-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-13-yl)-2-propene-1-one, 3-phenyl-1-(pyridin-14-yl)- 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-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 ) 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, and the like.

Specific examples of the compound represented by the general formula (1) applicable to the present invention, in which R ² 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 ... 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-(pyridin-4-yl)-2-propen-1-one, 1,3-bis(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)-1-(2-fluorophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(3-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, )-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-(4-iodophenyl)-2-propen-1-one, 3-(4-fluorophenyl)-1-(2-nitrophenyl)-2-propen 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-propen-1-one, 3-(4-fluorophenyl)-1-(4-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-[2-(trifluoromethoxy)phenyl]-2-propen-1-one, Examples of such compounds include 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, and 3-(4-fluorophenyl)-1-(4-biphenyl)-2-propen-1-one.

Specific examples of the compound represented by the general formula (1) applicable to the present invention in which R ¹ and R ² are bonded to form a ring include 9-fluorenone and 2-adamantanone.

Specific examples of the compound represented by the general formula (5) applicable to the present invention, in which R ² 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 the like. 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-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 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-pentafluoro-1-[4-(trifluoromethoxy)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 the compound represented by the general formula (5) applicable to the present invention, in which R ² 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, 2,2,3,3,3-pentafluoro-1-(thiophene-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-1-(3-fluorophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro 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-bromophenyl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(3-bromophenyl) 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 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-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-(trifluoro methoxy)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-yl)-1-phenylpropan-1-ol, 2,2,3,3,3-pentafluoro-1-(1,1'-biphenyl-4-yl)-1-phenylpropan-1-ol, and the like.

Specific examples of the compound represented by the general formula (5) applicable to the present invention, in which R ² 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, 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-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-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-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, 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-(3-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.

Specific examples of the compound represented by the general formula (5) applicable to the present invention, in which R ² 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, 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, phenyl)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, Pan-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, -ol, 2,2,3,3,3-pentafluoro-1-(2-nitrophenyl)-1-(3-methoxyphenyl)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)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)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, 2,2,3,3,3-pentafluoro-1-[3-(trifluoromethoxy)phenyl] yl]-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 the compound represented by the general formula (5) applicable to the present invention, in which R ² 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, 2,2,3,3,3-pentafluoro-1-(furan-3-yl)-1-(4-methoxyphenyl)propan-1-ol, 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-(4-chlorophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro-1-(4-chlorophenyl)-1-(4-methoxyphenyl)propan-1-ol, -(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-(3-iodophenyl)-1-(4-methoxyphenyl)propan-1-ol, 2,2,3,3,3-pentafluoro b-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-(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, 2,2,3,3,3-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 the compound represented by the general formula (5) applicable to the present invention, in which R ² 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, 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-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 the compound 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-(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-(thiophene (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-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 (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)-1-phenylpent-1-en-3-ol, (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-(trifluoro (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.

Represented by general formula (5) applicable to the present invention, R Specific examples of compounds in which ² is an (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-(thiophene-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol, and (E)-4,4,5,5,5-pentafluoro-3-(thiophene-3-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-(thiophen-3-yl)-1-(4-fluorophenyl)pent-1-en-3-ol 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) (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-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-fluoro phenyl)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-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-[3-(trifluoro methoxy)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.

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

Specific examples of bases that can be used in 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 used is preferably 1.1 to 3.0 moles per mole of carbonyl compounds used in the reaction.

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

The solvent applicable to the present invention is not particularly limited as long as it is inactive in the reaction, but specific examples 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. However, THF, DMF, and toluene are preferred, and they may be used alone or in combination, and the amount used is 5 to 50 times the weight of the carbonyl compounds and base used in the reaction.

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 range of -50°C to 40°C.
The mixing time of the carbonyl compound, base and pentafluoroethane used in the present invention varies depending on the type and structure of the micromixer (micromixer) used, for example, 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, taking into account 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.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

The following instruments were used for the analysis:
¹ H-NMR (300 MHz), ¹⁹ F-NMR (282 MHz), ¹³ C-NMR (125.8 MHz): Bruker Avance 500US, 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.

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 the gas flow control function is 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, 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, 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.

Each part was connected with a 1/16 inch joint.
The CF ₃ CF ₂ H 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 KHMDS and tBuOK solutions shown as "(KHMDS or tBuOK) in solvent" in FIG. 1 and the supply line for the carbonyl compound solution having the substituents R ¹ and R ² shown as "1,3,5 in solvent" in FIG. 1 were made of PTFE pipes with an inner diameter of 0.8 mm. The supply lines for the KHMDS or tBuOK solution and the supply line for the carbonyl compound solution may be supplied separately or together. When KHMDS and tBuOK are mixed and used, 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.

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)

A 4-bromobenzaldehyde solution (0.60 M) prepared by dissolving 4-bromobenzaldehyde (1a) (222 mg, 1.20 mmol) in anhydrous DMF (2.0 mL) was placed in a 5 mL gas-tight syringe and attached to a syringe pump (B-1). Similarly, a potassium tert-butoxide solution (0.60 M) prepared by dissolving potassium tert-butoxide (269 mg, 2.40 mmol) in DMF (4 mL) was placed in another gas-tight syringe and attached to a syringe pump (B-2).
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 (D-1 was used) cooled to −10° C. in advance using a thermostatic bath, while pentafluoroethane (0.1 MPa) was supplied to the mixer C at 15 mL/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 resulting organic layer was washed with saturated saline, dried over sodium sulfate, filtered, and concentrated under reduced pressure to obtain a 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.

The crude product obtained was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard, and the yield of the target compound, 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a), was found to be 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.

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, 1F), -130.0 (dd, ² J _FF , ³ J _FF =275.9, 17.2Hz, 1F) ppm.
MS (ESI, m/z) 306 [M+H] ⁺ .

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, a 4-bromobenzaldehyde solution (0.60 M) and a potassium tert-butoxide solution (0.60 M), while varying 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 reaction apparatus as in Example 1, 4-bromobenzaldehyde solution (0.60 M) was replaced with 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. In the ¹⁹ F-NMR measurement of the obtained crude product using benzotrifluoride as an internal standard, the yield of the target 2,2,3,3,3-pentafluoro-1-(4-bromophenyl)propan-1-ol (2a) was 89%.

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

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%).
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, 1F), -129.9 (dd, ² J _FF , ³ J _FF =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 (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, 1F), -129.9 (dd, ² J _FF , ³ J _FF =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 (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, 1F), -130.0 (dd, ² J _FF , ³ J _FF =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 (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, 1F), -129.8 (dd, ² J _FF , ³ J _FF =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 (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, 1F), -129.9 (dd, ² J _FF , ³ J _FF =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 (2 g)
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%).
^1H -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.
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, 1F), -129.7 (dd, ² J _FF , ³ J _FF = 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 (300 MHz, CDCl ₃ ) δ: 7.52 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 7.9 Hz, 2 H), 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, 1F), -129.9 (dd, ² J _FF , ³ J _FF = 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 (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=4.7Hz, 1H) 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, 1F), -129.6 (dd, ² J _FF , ³ J _FF =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%).
^1H -NMR (300MHz, _CDCl3 ) 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, 1F), -130.5 (dd, ² J _FF , ³ J _FF =274.1, 17.2Hz, 1F) ppm.
^13C -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 _CF , 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: [MH] ^- 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 target 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 = 7.9Hz, 1H) 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, 1F), -129.3 (dd, ² J _FF , ³ J _FF =275.0, 16.4Hz, 1F) ppm.
^13C -NMR (126MHz, _CDCl3 ) 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 _CF = 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 target product as a yellow liquid (31.7 mg, 0.137 mmol, yield 69%).
^1H -NMR (300MHz, _CDCl3 ) 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, 5.9Hz, 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, 1F), -130.5 (dd, ² J _FF , ³ J _FF =274.1, 17.2Hz, 1F) 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 _CF = 17.6 Hz) ppm.
ATR-FTIR (neat): n = 3426, 2923, 1432, 1355, 1208, 1131, 1023, 809, 708 cm ^-1 .
HRMS (ESI) m/z: [MH] ^- calcd. for C ₇ H ₄ F ₅ OS; 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)

Benzophenone (3a) (219 mg, 1.20 mmol) was dissolved in anhydrous DMF (2.0 mL) to prepare a benzophenone solution (0.60 M) which was then 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 then placed in another gas-tight syringe and attached to a syringe pump (B-2).

Acetophenone solution was supplied at 0.30 mL/min and potassium tert-butoxide solution was supplied at 0.60 mL to mixer C and microreactor D (D-1 was used) at room temperature, 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 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 a crude product of the target substance.
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.

The crude product thus obtained was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard, and the yield of the target compound, 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a), was found to be 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.

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 to 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, benzophenone solution (0.60 M) and potassium tert-butoxide solution (0.60 M) as in Example 21, while 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 reaction apparatus as in Example 21, the benzophenone solution (0.60M) was replaced with a benzophenone solution (0.90M) and fed at 0.33mL/min, potassium tert-butoxide solution (0.60M) was fed at 0.66mL/min, and pentafluoroethane (0.1MPa) was fed at 25.0mL/min, and the reaction was carried out at room temperature. In the ^19F -NMR measurement of the obtained crude product using benzotrifluoride as an internal standard, the yield of the target 2,2,3,3,3-pentafluoro-1,1-diphenylpropan-1-ol (4a) was 91%.

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

Examples 31 to 41 Reaction 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 of various aldehydes (0.60 M) shown in Table 4. The results are shown in Table 4.

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 (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 target 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 target 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, 1 H), 7.43-7.35 (m, 8 H), 4.03 (s, 1 H) 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, 1F) 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 J _{CF =} 288.4, 35.0 Hz), 117.7-112.6 (m), 80.6 (t, ² J _CF = 23.2 Hz) ppm.
ATR-FTIR (neat): n=3555, 3067, 1452, 1336, 1223, 1134, 1050, 910, 863, 755 cm ⁻¹ .
HRMS (ESI) m/z: [MH] ^- 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 target 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 = 7.1Hz, 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, 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 (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, 1F) 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 target 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, 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 (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, 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 (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, 1F), -117.8 (d, ² J _FF =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 (300 MHz, CDCl ₃ ) 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.
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 target 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=7.9Hz, 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 (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 (300 MHz, CDCl ₃ ) δ: 2.27-2.12 (m, 6H), 1.92-1.75 (m, 7H), 1.61 (d, J=12.4Hz, 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, a chalcone solution (0.3 M) prepared 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) prepared 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).

The chalcone solution was supplied at a rate of 0.33 mL/min and the KHMDS solution was supplied 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 supplied 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. Next, extraction was performed 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 a 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.

The resulting crude product was subjected to ¹⁹ F-NMR measurement using benzotrifluoride as an internal standard, and the yield of the target compound, (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a), was found to be 90%.
The obtained crude product was purified by silica gel column chromatography (hexane/dichloromethane=1/2 vol/vol) to obtain the target compound 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, 1F) ppm.
MS (ESI, m/z) 327 [MH] ^- .

Examples 43 to 45 Preparation of (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a) 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 in the same microflow reactor as in Example 42. The results are shown in Table 5.

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 compound, (E)-4,4,5,5,5-pentafluoro-1,3-diphenylpent-1-en-3-ol (6a), in a yield of 90%.
Examples 47 to 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.

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 the 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 Reaction of various chalcones The target products were 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. Note that in Example 55, the reaction was carried out using 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 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%).
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, 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 (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 obtained 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%).
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 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 liquid (25.2 mg, 0.0693 mmol, yield 70%).
^1H -NMR (300MHz, _CDCl3 ) δ: 7.61 (dd, J=8.8, 5.3Hz, 2H), 7.41-7.36 (m, 2H), 7.12-7.01 (m, 4 H), 6.80 (d, J = 15.9 Hz, 1H), 6.73 (d, J = 16.2 Hz, 1H), 2.71 (s, 1H) 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 obtained crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1 vol/vol) to obtain the target compound 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, 1F) ppm.
MS (ESI, m/z) 372 [MH] ^- .

The pentafluoroethyl group-containing compounds obtained by the method of the present invention are useful as manufacturing intermediates in the fields of medicine, agrochemicals, and electronic materials.

A: Mass flow controller B-1, B-2: Syringe pump C: Micro mixer D: Micro reactor

Claims (4)

The following general formula (1)

[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):

(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):

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

(In formula (4), ^R5 represents a hydrogen atom or a methoxy group, and ^R1 and ^R2 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)

[In the 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):

(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):

(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), ^R5 represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a trifluoromethyl group, a methoxy group, or a trifluoromethoxy group), and ^R1 and ^R2 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. The method for producing a pentafluoroethyl group-containing compound according to claim 1, characterized in that the organic solvent is toluene, tetrahydrofuran, and/or N,N-dimethylformamide. 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. 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.