JPH09295948A - Production of fluorine-containing compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a fluorine-containing compound useful as a synthetic intermediate for a medicine, a chemical or a functional material, by carrying out the functional replacement reaction of an α-perfluoroalkylated alcohol derivative, which has been regarded to be difficult, in the presence of a specific compound. SOLUTION: A sulfonic acid ester of an α-perfluoroalkylated alcohol of formula I (R<1> and R<2> are each H, an alkyl, an aromatic group, an aralkyl, an alkenyl or R<1> and R<2> form a ring with an adjoining carbon atom; Rf is a perfluoroalkyl; R<3> is an alkyl, an aromatic group or a halogen) is reacted with a nucleophilic reagent of the formula HY [Y is Q<1> R<4> , Q<2> R<5> R<6> (Q<1> is O, S, selenium or tellurium; Q<2> is N, P or arsine; R<4> to R<6> are each H, alkyl, an aromatic group, etc.; R<5> and R<6> form a ring) in the presence of a basic substance to give a fluorine-containing compound of formula II. NaOH, KF, phenyllithium may be cited as the basic substance. For example, a compound of formula V is obtained from a compound of formula III and a compound of formula IV by using the method.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a method for producing a fluorine-containing compound, which is useful as a pharmaceutical or agricultural chemical such as an anticancer agent or an enzyme inhibitor, or a synthetic intermediate for a functional material such as a ferroelectric liquid crystal.

[0002]

2. Description of the Related Art Many compounds having a fluorine-containing atomic group such as a perfluoroalkyl group in a molecule are known to exhibit specific physiological activities and physical properties. Has attracted attention as a functional material such as a liquid crystal. Many methods have been reported for introducing a perfluoroalkyl group such as a trifluoromethyl group into an organic compound. Above all, a method of reacting a perfluoroalkyl anion equivalent such as a perfluoroalkylsilane with a carbonyl compound to obtain an alcohol derivative having a perfluoroalkyl group at the α-position uses a relatively inexpensive reagent under mild conditions. Since the reaction proceeds in good yield, it can be said that this is one of the excellent perfluoroalkyl group introduction methods (Kenji Uneyama,
Coupling, 49, 7, 612 (1991): R. Krishnamurti et al., J.
Org. Chem., 56, 984 (1991): Toshiki Hagiwara, Takamasa Fuchigami,
JP-A-7-118188). Recently, an optically active fluorine-containing epoxide has been expected as a building block of an optically active fluorine-containing compound, which can be opened to an optically active α-perfluoroalkylated alcohol derivative (C. Busscheme). -Hunnefeld et al, Ch
em. Ber., 125, 2795 (1992): Takeshi Endo et al., Japanese Patent Laid-Open No. 7-1657
50).

[0003] However, it is known that α-perfluoroalkylated alcohol derivatives obtained by these methods are different from ordinary alcohols in that conversion of hydroxyl functional groups hardly proceeds due to the strong electron-withdrawing property of perfluoroalkyl groups. ing. For example, in ordinary alcohols, a hydroxyl group is converted into a sulfonic acid ester having a high elimination ability, and then functional groups of the hydroxyl group can be converted and carbon-carbon bonds can be formed by reacting with various nucleophiles. It is a very general method in chemistry (Ed. By DN Jones, Co
mprehensive Organic Chemistry, Vol. 3, p341, Perga
mon Press (1979): T. Sato, J. Otera, Synlett, 336
(1995): T. Sato, J. Otera, J. Org. Chem., 60, 262.
7 (1995)). However, sulfonic acid esters of α-perfluoroalkylated alcohols are extremely difficult to undergo nucleophilic attack, and it is not possible to obtain a fluorine-containing compound in which the sulfonyloxy group is substituted with another atomic group. As described above, the α-perfluoroalkylated alcohol derivative is a compound whose functional group conversion is very difficult, which significantly limits the applicable range of the above-mentioned perfluoroalkyl group introduction reaction, and poses a great obstacle to the development of this field. Had become.

[0004]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a highly versatile method for easily and inexpensively achieving a functional group conversion reaction of an α-perfluoroalkylated alcohol derivative, which has hitherto been difficult. It is in.

[0005]

Means for Solving the Problems As a result of intensive studies to solve the above-mentioned drawbacks of the prior art, the present inventors have found that α-perfluoroalkyl is allowed to coexist with a basic substance in the reaction system. It was found that the functional group conversion reaction of a fluorinated alcohol derivative can be achieved inexpensively and easily, and the present invention has been completed.

That is, the present invention provides a compound represented by the general formula R ¹ R ² R _f C-OSO ₂ -R ³ (I) (wherein R ¹ and R ² each independently have a hydrogen atom or a substituent). Represents an alkyl group, an aromatic group, an aralkyl group, an alkenyl group, or an alkynyl group.
Further, R ¹ and R ² may form a ring together with the carbon atom to which they are bonded.
R _f represents a perfluoroalkyl group. R ³ represents an alkyl group which may have a substituent, an aromatic group, or a halogen atom. ) A sulfonic acid ester of an α-perfluoroalkylated alcohol represented by the general formula HY (II) (wherein Y represents —Q ¹ R ⁴ or —Q ² R ⁵ R ⁶ ) in the presence of a basic substance. However, Q ¹ represents an oxygen atom, a sulfur atom, a selenium atom or a tellurium atom, Q ² represents a nitrogen atom, a phosphorus atom or an arsenic atom, and R ⁴ , R ⁵ and R ⁶ each independently represent hydrogen. An atom or an alkyl group which may have a substituent, an aromatic group, an aralkyl group, an alkenyl group, an alkynyl group, or an acyl group, and R ⁵ and R ⁶ are each an atom to which they are bonded; Which may form a ring together) with a general formula R ¹ R ² R _f CY (III) (wherein R ¹ , R ^2, R _f and Y are the same as above Represented by a.) In a process for preparing a fluorine-containing compound.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula (I), general formula (II) and general formula (III),
The alkyl group in R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ is
It is an optionally branched alkyl group or cycloalkyl group having 1 to 20 carbon atoms, which may have a substituent. The aromatic group represents an aromatic hydrocarbon group and a heterocyclic aromatic group, and may include a phenyl group, a naphthyl group, an anthryl group, an anthryl group, a pyridyl group, a furyl group, a thienyl group, which may have a substituent. Can be illustrated. Examples of the aralkyl group include benzyl group, pentafluorobenzyl group, p-methylbenzyl group, p-nitrobenzyl group, m-nitrobenzyl group, o-nitrobenzyl group, naphthylmethyl group, furfuryl group and α-phenethyl group. It can be illustrated. The alkenyl group, vinyl group, β-styryl group, 1-propenyl group, 1-butenyl group, 1-hexenyl group, 1-octenyl group,
Examples include 1-decenyl group, 1-cyclohexenyl group, allyl group, methallyl group, cinnamyl group, 2-butenyl group, 2-hexenyl group, 2-octenyl group, 2-decenyl group, 2-cyclohexenyl group, etc. You can Examples of the alkynyl group include ethynyl group, phenylethynyl group, 2-propynyl group and the like. The acyl group, formyl group, acetyl group, butyryl group, acryloyl group, benzoyl group,
A toluyl group etc. can be illustrated. When R ¹ and R ² or R ⁵ and R ⁶ are united with the atom to which they are bonded to form a ring, a butylene group,
Examples thereof include a pentamethylene group, a hexamethylene group, an o-xylylene group, a succinyl group, and a phthaloyl group. As a substituent in any of the above groups, an optionally branched alkyl group having 1 to 10 carbon atoms, an aromatic group,
Examples thereof include a halogen atom, a hydroxyl group, an alkoxy group, an amino group, a nitro group, an azido group, an acyl group, a formyl group, a carboxyl group, a cyano group, a thiol group, an alkylthio group, a phosphino group and a silyl group.

The general formula (I) and the general formula (III)
R _f is a perfluoroalkyl group or a perfluorocycloalkyl group having 1 to 20 carbon atoms which may be branched, and examples thereof include trifluoromethyl group, pentafluoroethyl group, heptafluoropropyl group, nonafluorobutyl group. Group, heptadecafluorooctyl group, heptafluoroisopropyl group, undecafluorocyclohexyl group and the like.

R ³ in the general formula (I) is a methyl group, an ethyl group, a propyl group, a trifluoromethyl group,
Pentafluoroethyl group, nonafluorobutyl group, 2,2,
2-trifluoroethyl group, phenyl group, p-tolyl group, p-
Examples thereof include a chlorophenyl group, a p-bromophenyl group, a p-fluorophenyl group, a p-nitrophenyl group, a 2,4,6-trinitrophenyl group, a pentafluorophenyl group and a fluorine atom.

A method for synthesizing a sulfonic acid ester of an α-perfluoroalkylated alcohol represented by the general formula (I) is known (RK Crossland, KL Servis, J. Org.
Chem., 35, 3195 (1970)), and can be easily synthesized by a method similar to the conventionally known sulfonic acid ester of a hydrocarbon alcohol. That is, α
-Perfluoroalkylated alcohol and the corresponding sulfonic acid chloride or sulfonic anhydride, pyridine,
In the presence of a base such as triethylamine, dichloromethane,
The reaction may be carried out in a solvent that does not participate in the reaction, such as carbon tetrachloride and ether.

In the method of the present invention, an optically active substance may be used as the sulfonic acid ester of the substrate for the synthesis of the optically active substance.

The amount of the nucleophile represented by the general formula (II) used is arbitrary, but from the viewpoint of yield, it is preferably 1 equivalent or more with respect to the sulfonate ester of the substrate.

The present invention has an essential condition that it is carried out in the presence of a basic substance. As the basic substance, metal hydroxides such as sodium hydroxide and potassium hydroxide, basic salts such as potassium carbonate and sodium hydrogen carbonate, fluoride salts such as potassium fluoride, cesium fluoride and tetrabutylammonium fluoride. , Sodium methylate, potassium-ter
Examples thereof include metal alcoholates such as t-butylate, organic metal compounds such as n-butyllithium, phenyllithium, and ethylmagnesium bromide. The amount of these basic substances used is arbitrary, but from the viewpoint of yield, it is preferably 1 equivalent or more with respect to the sulfonate ester of the substrate.

In carrying out the present invention, it is preferable to carry out in a solvent that does not participate in the reaction, and ether, chloroform, tetrahydrofuran (THF), acetonitrile, propionitrile, dimethylformamide (DMF), dimethylsulfoxide (DMSO), N are used. -Methylpyrrolidone (NMP),
It is more preferable to carry out in an aprotic polar solvent such as dimethylacetamide (DMAc), phosphoric acid hexamethyltriamide (HMPA), and tetramethylurea (TMU).

The reaction temperature can be appropriately selected from the range of -100 ° C. to 200 ° C.
A range of 50 ° C. is preferred.

[0016]

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

Embodiment 1

[0018]

Embedded image

Methane sulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride (0.304 g, 2.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent, and under argon atmosphere, 1
The reaction was carried out at 20 ° C for 61 hours. Benzotrifluoride was added to the reaction mixture as an internal standard substance, and ¹⁹ F-NMR was measured.The desired 2,2,2-trifluoro-1-phenylethyl benzoate was produced in a yield of 27.1%. It became clear. The reaction mixture was further extracted with ethyl acetate / water, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give a crude product. Obtained. Future collection
The desired product was isolated by GLC and subjected to various instrumental analyzes. 2,2,2-Trifluoro-1-phenylethyl benzoate ¹ H-NMR (CDCl ₃ , TMS): δ = 6.37 (q, J = 6.9 Hz, 1H), 7.4
0-7.66 (m, 8H), 8.11-8.15 (m, 2H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -76.34 (d, J = 6.9 Hz)

Embodiment 2

Methane sulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), benzoic acid (0.122 g, 1.00 mmol), potassium fluoride (0.058 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent, and under an argon atmosphere, 1
The reaction was carried out at 20 ° C for 87 hours. GLC analysis was performed by adding n-dodecane as an internal standard substance to the reaction mixture, and the desired benzoic acid 2,2,2-trifluoro was obtained in a yield of 40.8%.
It became clear that -1-phenylethyl was produced.

Example 3

Methanesulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), benzoic acid (0.122 g, 1.00 mmol), potassium fluoride (0.145 g, 2.50 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent, and under an argon atmosphere, 1
The reaction was carried out at 20 ° C for 87 hours. GLC analysis was performed by adding n-dodecane as an internal standard substance to the reaction mixture, and the target benzoic acid 2,2,2-trifluoro was obtained in a yield of 57.6%.
It became clear that -1-phenylethyl was produced.

Example 4

[0025] Methanesulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride (0.152 g, 1.00 mmol), and N-methylpyrrolidone (NMP, 2.0 ml) as a solvent were added, and an argon atmosphere was used to
The reaction was carried out at 39 ° C for 39 hours. When n-dodecane was added to the reaction mixture as an internal standard substance and GLC analysis was carried out, 2
It was revealed that the target 2,2,2-trifluoro-1-phenylethyl benzoate was produced in a yield of 6.2%.

Example 5

[0027]

Embedded image

Methane sulfonic acid in a test tube with a cap
1,1,1-Trifluoro-2-octyl (0.131 g, 0.50 mmo
l), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride
(0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the atmosphere was maintained at 120
The reaction was performed at 115 ° C for 115 hours. When n-dodecane was added to the reaction mixture as an internal standard substance and GLC analysis was carried out, 2
It was revealed that the target 1,1,1-trifluoro-2-octyl benzoate was produced in a yield of 0.7%. The reaction mixture was further extracted with ethyl acetate / water, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give a crude product. Obtained. The desired product was isolated from this by preparative GLC and subjected to various instrumental analyzes. 1,1,1-Trifluoro-2-octyl benzoate ¹ H-NMR (CDCl ₃ , TMS): δ = 0.86 (m, 3H), 1.26-1.43 (m,
8H), 1.83-1.94 (m, 2H), 5.56 (q, J = 6.7 Hz, 1H), 7.43-
7.66 (m, 3H), 8.06-8.12 (m, 2H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -77.52 (d, J = 6.7 Hz)

Example 6

[0030]

Embedded image

In a test tube with a cap, 1,1,1-trifluoro-2-octyl trifluoromethanesulfonate (0.158 g,
0.50 mmol), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride (0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was performed at room temperature for 41 hours under an argon atmosphere. It was GLC analysis was performed by adding n-dodecane as an internal standard substance to the reaction mixture, and the target benzoic acid 1,1,1-trifluoro was obtained in a yield of 41.5%.
-2-It was revealed that octyl was produced.

Example 7

[0033]

Embedded image

In a test tube with a cap, 1,1,1-trifluoro-2-octyl trifluoromethanesulfonate (0.158 g,
0.50 mmol), phthalimide (0.147 g, 1.00 mmol), cesium fluoride (0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was carried out at 60 ° C for 16 hours under an argon atmosphere. It was Benzotrifluoride was added to the reaction mixture as an internal standard, and ¹⁹ F-
When NMR was measured, the target N- (1,1,1-
It was revealed that trifluoro-2-octyl) phthalimide was produced. The reaction mixture was further extracted with ethyl acetate / water, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give a crude product. Obtained. The desired product was isolated from this by preparative GLC and subjected to various instrumental analyzes. N- (1,1,1-trifluoro-2-octyl) phthalimide ¹ H-NMR (CDCl ₃ , TMS): δ = 0.85 (m, 3H), 1.15-1.39 (m,
8H), 1.86-2.02 (m, 1H), 2.52-2.61 (m, 1H), 4.73 (m, 1
H), 7.73-7.94 (m, 4H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -72.90 (d, J = 8.1 Hz) MS: m / z (rel. Int.) = 313 (M ⁺ , 100), 209 (49), 160 (4
1), 148 (69), 130 (64), 105 (47), 104 (27), 76 (23), 41
(twenty four)

Example 8

[0036]

Embedded image

Methane sulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), thiophenol (0.275 g, 2.50 mmol), potassium fluoride (0.145 g, 2.50 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent, and the reaction was carried out at 60 ° C for 6 hours under an argon atmosphere. It was GLC analysis was performed by adding n-dodecane as an internal standard substance to the reaction mixture, and the target 1,1,1-trifluoro-2-phenyl-2- (phenylthio) ethane was produced in a yield of 59.9%. It became clear. The reaction mixture is further mixed with ethyl acetate /
Extracted with water, the organic layer is a saturated aqueous sodium hydrogen carbonate solution,
After washing with saturated saline, it was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure with heating to obtain a crude product. The desired product was isolated from this by preparative GLC and subjected to various instrumental analyzes. 1,1,1-Trifluoro-2-phenyl-2- (phenylthio) ethane ¹ H-NMR (CDCl ₃ , TMS): δ = 4.52 (q, J = 8.5 Hz, 1H), 7.2
5-7.46 (m, 10H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -68.25 (d, J = 8.5 Hz) MS: m / z (rel. Int.) = 268 (M ⁺ , 88 ), 199 (7), 159 (100),
109 (42)

Example 9

[0039]

[Chemical 6]

A hexane solution of butyllithium (1.56 M, 1.39 ml, 2.16 mmol) was placed in a flask purged with argon to 0 ° C., and phenylphosphine (0.108 ml, 0.983 mmo) was added.
l), 1,1,1,6,6,6-hexafluoro-2,5-bis (trifluoromethanesulfonyloxy) hexane (0.2
A solution of 41 g, 0.492 mmol) in tetrahydrofuran (THF, 2 ml) was added, and the mixture was stirred at 70 ° C for 24 hours. After the reaction, ether was added to remove insoluble matter by filtration, and the solvent was distilled off from the filtrate by heating under reduced pressure to obtain a crude product. After confirming the formation of the desired 1-phenyl-2,5-bis (trifluoromethyl) phosphorane by NMR spectroscopy, we attempted a more stable oxidation to P-oxide for isolation. That is, the crude phospholane was dissolved in dichloromethane (10 ml), 31% aqueous hydrogen peroxide was added, and the mixture was stirred at room temperature for 8 hours. The reaction mixture was washed with an aqueous sodium hydrogen sulfite solution, the organic layer was dried, and the solvent was evaporated under reduced pressure and the resulting crude product was subjected to silica gel column chromatography to obtain the desired 1-phenyl-
2,5-Bis (trifluoromethyl) phosphorane P-oxide was obtained as a colorless solid in a yield of 19%. 1-Phenyl-2,5-bis (trifluoromethyl) phosphorane ¹ H-NMR (CDCl ₃ , TMS): δ = 1.83-3.50 (m, 6H), 7.34-7.6
3 (m, 5H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -66.09 (ddd, J = 22.2 Hz,
10.5 Hz, 1.3 Hz, 2.4F), -65.46 (dd, J = 21.4 Hz, 10.6
Hz, 1.2F), -61.08 (t, J = 8.2 Hz, 2.4F) ³¹ P-NMR (CDCl ₃ , PPh ₃ = -5.47 ppm): δ = -9.44 (m) 1-phenyl-2,5- Bis (trifluoromethyl) phosphorane P-oxide ¹ H-NMR (CDCl ₃ , TMS): δ = 1.87-3.40 (m, 6H), 7.52-7.8
6 (m, 5H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -62.74 (dd, J = 9.4 Hz, 7.
1 Hz, 2.4F), -62.29 (dd, J = 8.5 Hz, 6.4 Hz, 2.4F),-
62.01 (dd, J = 9.2 Hz, 6.3 Hz, 1.2F) ³¹ P-NMR (CDCl ₃ , PPh ₃ = -5.47 ppm): δ = 42.15 (m)

Example 10

[0042]

Embedded image

In a test tube with a cap, 1,1,1-trifluoro-2-octyl (R) -trifluoromethanesulfonate (0.158)
g, 0.50 mmol), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride (0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent, and the reaction was carried out at room temperature for 40 hours under an argon atmosphere. Was done. GLC analysis was performed by adding n-dodecane as an internal standard substance to the reaction mixture, and it was revealed that the target 1,1,1-trifluoro-2-octyl benzoate was produced in a yield of 45.0%. It became The reaction mixture was further extracted with ethyl acetate / water, the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give a crude product. Obtained. The desired product was isolated from this by preparative thin layer chromatography and analyzed by high performance liquid chromatography using an optically active column (Daicel CHIRALPAK AD). As a result, (S) -benzoic acid with an optical yield of enantiomeric excess of 96% or more was obtained. It was revealed that 1,1,1-trifluoro-2-octyl acid was produced.

Comparative Example 1

Methane sulfonic acid in a test tube with a cap
2,2,2-Trifluoro-1-phenylethyl (0.127 g, 0.50
mmol), benzoic acid (0.122 g, 1.00 mmol) and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was carried out at 120 ° C. for 24 hours under an argon atmosphere. GLC analysis of the reaction mixture was performed to find that benzoic acid 2,2,2-trifluoro
Formation of -1-phenylethyl was not observed.

Example 11

[0047]

Embedded image

In a test tube with a cap, 1,1,1-trifluoro-2-octyl trifluoromethanesulfonate (0.158 g,
0.50 mmol), benzylthiol (0.124 g, 1.00 mmol),
Cesium fluoride (0.152 g, 1.00 mmol) and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was carried out at 60 ° C. for 24 hours under an argon atmosphere. Benzotrifluoride was added as an internal standard to the reaction mixture,
^{When 19} F-NMR was measured, the target 1,1,1-
It was revealed that trifluoro-2- (benzylthio) octane was produced. The reaction mixture was further extracted with ethyl acetate / water, the organic layer was washed with saturated brine, and then the desired product was isolated by preparative thin layer chromatography and subjected to various instrumental analyzes. 1,1,1-Trifluoro-2- (benzylthio) octane ¹ H-NMR (CDCl ₃ , TMS): δ = 0.85 (m, 3H), 0.98-1.29 (m,
6H), 1.37-1.51 (m, 2H), 1.60-1.79 (m, 2H), 2.67-2.87
(m, 1H), 3.82 (bs, 1H), 7.20-7.39 (m, 5H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -71.06 (d, J = 8.3 Hz)

Example 12

[0050]

Embedded image

In a test tube with a cap, 1,1,1-trifluoro-2-octyl trifluoromethanesulfonate (0.158 g,
0.50 mmol), 4-hydroxybenzoic acid (0.138 g, 1.00 mmo
l), cesium fluoride (0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was carried out at room temperature for 24 hours under an argon atmosphere. Benzotrifluoride was added to the reaction mixture as an internal standard substance, and ¹⁹ F-NMR was measured.
It was revealed that 1,1,1-trifluoro-2-octyl hydroxybenzoate was produced. The reaction mixture was further extracted with ether / water, the organic layer was washed with saturated brine, and then the desired product was isolated by preparative thin layer chromatography and subjected to various instrumental analyzes. 4-Hydroxybenzoic acid 1,1,1-trifluoro-2-octyl ¹ H-NMR (CDCl ₃ , TMS): δ = 0.86 (m, 3H), 1.21-1.43 (m,
8H), 1.81-1.92 (m, 2H), 5.43-5.60 (m, 1H), 6.50 (b, 1
H), 6.90 (dm, J = 8.8 Hz, 2H), 7.99 (dm, J = 8.8 Hz, 2H) ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -77.51 (d, J = 6.7 Hz)

Example 13

[0053]

Embedded image

Test tubes with caps were charged with 3,3,4,4,4-pentafluoro-2-butyl trifluoromethanesulfonate (0.148
g, 0.50 mmol), benzoic acid (0.122 g, 1.00 mmol), cesium fluoride (0.152 g, 1.00 mmol), and dimethylformamide (DMF, 2.0 ml) as a solvent were added, and the reaction was carried out at room temperature under an argon atmosphere for 48 hours. Was done. Benzotrifluoride was added to the reaction mixture as an internal standard, and ¹⁹ F-NMR
The target benzoic acid 3,3,3 was obtained with a yield of 38.7%.
It was revealed that 4,4,4-pentafluoro-2-butyl was produced. Benzoic acid 3,3,4,4,4-pentafluoro-2-butyl ¹⁹ F-NMR (CDCl ₃ , CFCl ₃ ): δ = -129.45 (dd, J = 280 Hz, 1
6.0 Hz, 1F), -122.25 (ddd, J = 280 Hz, 7.9 Hz, 2.3 H
z, 1F), -82.51 (s, 3F)

[0055]

The present invention provides a simple method for producing a fluorine-containing compound, which is useful as a pharmaceutical or agricultural chemical such as an anticancer agent or an enzyme inhibitor, or a synthetic intermediate for a functional material such as a ferroelectric liquid crystal. .

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07B 53/00 7419-4H C07B 53/00 C C07C 67/11 C07C 67/11 69/78 69 / 78 319/14 7419-4H 319/14 323/07 7419-4H 323/07 C07D 209/48 C07F 9/6568 C07F 9/6568 C07B 61/00 300 // C07B 61/00 300 C07D 209/48 Z C07M 7 : 00

Claims (1)

[Claims] 1. A compound represented by the general formula R ¹ R ² R _f C—OSO ₂ —R ³ (wherein R ¹ and R ² are each independently a hydrogen atom or an alkyl group which may have a substituent, an aromatic group). Represents a group, an aralkyl group, an alkenyl group, or an alkynyl group.
Further, R ¹ and R ² may form a ring together with the carbon atom to which they are bonded.
R _f represents a perfluoroalkyl group. R ³ represents an alkyl group which may have a substituent, an aromatic group, or a halogen atom. ), A sulfonic acid ester of an α-perfluoroalkylated alcohol represented by the general formula HY (in the formula, Y represents -Q ¹ R ⁴ or -Q ² R ⁵ R ⁶ ; Q ¹ represents an oxygen atom, a sulfur atom, a selenium atom or a tellurium atom, Q ² represents a nitrogen atom, a phosphorus atom or an arsenic atom, and R ⁴ , R ⁵ and R ⁶ are each independently a hydrogen atom or a substituent. Represents an alkyl group which may have a group, an aromatic group, an aralkyl group, an alkenyl group, an alkynyl group, or an acyl group, and R ⁵ and R ⁶ are each integrated with the atom to which they are bonded. May form a ring.) With a nucleophile represented by the general formula R ¹ R ² R _f CY (wherein R ¹ , R ² , R _f and Y is the same as above.) A method for producing a fluorine-containing compound.