JP5067780B2 - Process for producing quinolines having a perfluoroalkyl group - Google Patents

Description

  The present invention relates to a method for producing a quinoline having a perfluoroalkyl group.

Quinolines having a perfluoroalkyl group have unique properties and are used in various fields such as pharmaceutical and agrochemical synthesis intermediates (Patent Document 1), organic nonlinear optical materials (Patent Document 2), and luminescent materials (Patent Document 3). It is an industrially important compound used. Therefore, methods for directly introducing perfluoroalkyl groups, particularly trifluoromethyl groups, into quinolines have been studied.
For example, Patent Document 4 discloses that 8-hydroxy-5-trifluoromethylquinoline can be produced by reacting trifluoromethyl bromide with 8-hydroxyquinoline in the presence of sodium dithionite. . This method has a problem in that the yield is low despite the reaction conditions of 10 atm or more. Non-Patent Document 1 discloses that 8-amino-5-trifluoromethylquinoline and 8-amino-7-trifluoro are reacted by reacting trifluoromethyl iodide with 8-aminoquinoline in the presence of zinc-sulfur dioxide. It is disclosed that a mixture of methylquinolines is obtained. In this method, since a highly toxic sulfur compound is used, it is difficult to use on an industrial scale.
EP 427605 Specification JP-A-3-284734 JP 11-279152 A Japanese Patent Laid-Open No. 1-100135 Journal of Heterocyclic Chemistry, Vol. 31, pp. 1413-1416, 1994. There have been no reports on 5,7-bis (perfluoroalkyl) -8-hydroxyquinoline and 5,7-bis (perfluoroalkyl) -8-aminoquinoline.

  An object of the present invention is to develop a simple and efficient production method of quinolines having a perfluoroalkyl group.

  The present invention relates to a general formula (1)

[Wherein, R ^1a and R ^1b represent an alkyl group having 1 to 12 carbon atoms or an optionally substituted phenyl group. ]
In the presence of sulfoxides, peroxides, iron compounds, and optionally acids,
General formula (2)

[Wherein, Rf represents a perfluoroalkyl group having 1 to 6 carbon atoms, and X represents a halogen atom. ]
Perfluoroalkyl halides represented by:
General formula (3)

[Wherein, R ² represents a hydrogen atom, a hydroxyl group, or an amino group which may be substituted with one or two alkyl groups having 1 to 4 carbon atoms. ]
With a quinoline represented by
General formula (4)

Wherein, Rf and ^{R 2} represents the same content as the, n represents 1 or 2. ]
It is related with the manufacturing method of the quinoline which has a perfluoroalkyl group characterized by obtaining the quinoline which has the perfluoroalkyl group represented by these.

  INDUSTRIAL APPLICABILITY The present invention can provide quinolines having a perfluoroalkyl group useful as an intermediate for medicines and agricultural chemicals and a method for producing them easily and efficiently.

  In the present invention, as a reaction reagent, quinolines are formed in a single step with a perfluoroalkyl halide in the presence of a sulfoxide represented by the above general formula (1), a peroxide, an iron compound, and, optionally, an acid. Perfluoroalkylation produces quinolines having a perfluoroalkyl group.

Here, in the sulfoxides represented by the general formula (1) constituting the reaction reagent, the alkyl group having 1 to 12 carbon atoms represented by R ^1a and R ^1b specifically includes a methyl group and a butyl group. And dodecyl group. Specific examples of the optionally substituted phenyl group represented by R ^1a and R ^1b include a phenyl group, a p-tolyl group, an m-tolyl group, and an o-tolyl group. R ^1a and R ^1b are preferably a methyl group, a butyl group, or a phenyl group, and more preferably a methyl group, in terms of a good yield.

  Specific examples of the sulfoxides represented by the general formula (1) include dimethyl sulfoxide, dibutyl sulfoxide, di-sec-butyl sulfoxide, methylphenyl sulfoxide, (R)-(+)-methyl-p-tolyl sulfoxide, ( S)-(−)-methyl-p-tolyl sulfoxide, diphenyl sulfoxide and the like. As the sulfoxides, dimethyl sulfoxide, dibutyl sulfoxide, and diphenyl sulfoxide are preferable, and dimethyl sulfoxide is more preferable in terms of good yield and low cost.

Examples of the peroxide constituting the reaction reagent include hydrogen peroxide, hydrogen peroxide-urea complex, t-butylperoxide, and peracetic acid. These may be used in combination as necessary. Good. From the viewpoint of good yield, hydrogen peroxide or hydrogen peroxide-urea complex is preferable.
Hydrogen peroxide may be diluted with water. The concentration at that time may be 3 to 70% by weight, but a commercially available 35% by weight aqueous solution may be used as it is. It is more preferable to dilute with water to 10 to 30% by weight in terms of good yield and safety.

Further, the iron compound constituting the reaction reagent is preferably an iron (II) salt in terms of a good yield, for example, iron (II) sulfate, iron (II) ammonium sulfate, iron (II) tetrafluoroborate, iron chloride. Inorganic salts such as (II), iron bromide (II) or iron (II) iodide, iron (II) acetate, iron (II) oxalate, iron (II) bisacetylacetonate, ferrocene, bis ( organometallic compounds such as (η ⁵ -pentamethylcyclopentadienyl) iron and the like may be mentioned, and these may be used in appropriate combination. Further, iron powder or iron (I) salt and an oxidizing reagent such as peroxide can be combined to generate iron (II) salt in the system. In that case, the peroxide which comprises the reaction reagent of this invention can also be used as an oxidizing reagent as it is.
Among the above iron compounds, iron sulfate (II), iron (II) ammonium sulfate, iron (II) tetrafluoroborate, ferrocene, and bis (η ⁵ -pentamethylcyclopentadienyl) iron in terms of good yield It is preferable to use iron powder.
These iron compounds may be used as solids, but can also be used as solutions. When used as a solution, the solvent may be any of the solvents described below, but water is particularly preferable. In this case, the concentration of the iron compound solution is preferably 0.1 to 10 mol / L, and more preferably 0.5 to 5 mol / L.

The use ratio of each component in the above reaction reagent is as follows.
That is, the molar ratio between the quinoline represented by the general formula (3) and the sulfoxide is preferably 1: 1 to 1: 200, and more preferably 1:10 to 1: 100 in terms of a good yield. .
The molar ratio of the quinolines to the peroxide is preferably 1: 0.1 to 1:10, and more preferably 1: 1.5 to 1: 3 in terms of a good yield.
Furthermore, the molar ratio of the quinolines to the iron compound is preferably 1: 0.01 to 1:10, and more preferably 1: 0.1 to 1: 1 in terms of a good yield.

The yield of the target product may be improved by adding an acid to the reaction reagent used in the present invention. The acid to be added is inorganic acid such as sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, phosphoric acid, hexafluorophosphoric acid or tetrafluoroboroboric acid, formic acid, acetic acid, propionic acid, oxalic acid, Any of organic acids such as p-toluenesulfonic acid, trifluoromethanesulfonic acid or trifluoroacetic acid may be used, and these may be used in combination as appropriate. It is desirable to use sulfuric acid alone in terms of good yield.
These acids may be used after diluting. The solvent at that time may be any of the solvents described later, and water or the above sulfoxides are particularly desirable. The concentration of the acid when diluted is preferably 0.1 to 10 mol / L, and more preferably 0.5 to 5 mol / L.
The molar ratio of the quinoline to the acid to be added is preferably 1: 0.001 to 1: 5, and more preferably 1: 0.01 to 1: 2 in terms of a good yield.

  Next, the starting materials of the quinolines having a perfluoroalkyl group of the present invention are halogenated perfluoroalkyls represented by the above general formula (2) and quinolines represented by the above general formula (3). is there.

  Here, in the general formula (2), the perfluoroalkyl group having 1 to 6 carbon atoms represented by Rf is specifically a trifluoromethyl group, a perfluoroethyl group, a perfluoropropyl group, or a perfluoroisopropyl group. Perfluorocyclopropyl group, perfluorobutyl group, perfluoroisobutyl group, perfluoro-sec-butyl group, perfluoro-tert-butyl group, perfluorocyclobutyl group, perfluorocyclopropylmethyl group, perfluoropentyl group Perfluoro-1,1-dimethylpropyl group, perfluoro-1,2-dimethylpropyl group, perfluoroneopentyl group, perfluoro-1-methylbutyl group, perfluoro-2-methylbutyl group, perfluoro-3- Methylbutyl group, perfluorocyclobutyl Til group, perfluoro-2-cyclopropylethyl group, perfluorocyclopentyl group, perfluorohexyl group, perfluoro-1-methylpentyl group, perfluoro-2-methylpentyl group, perfluoro-3-methylpentyl group, Perfluoroisohexyl group, perfluoro-1,1-dimethylbutyl group, perfluoro-1,2-dimethylbutyl group, perfluoro-2,2-dimethylbutyl group, perfluoro-1,3-dimethylbutyl group, Perfluoro-2,3-dimethylbutyl group, perfluoro-3,3-dimethylbutyl group, perfluoro-1-ethylbutyl group, perfluoro-2-ethylbutyl group, perfluoro-1,1,2-trimethylpropyl group Perfluoro-1,2,2-trimethylpropyl group, perfluoro-1-ethyl -1-methylpropyl group, etc. perfluoro-1-ethyl-2-methylpropyl group or a perfluoroalkyl cyclohexyl group can be exemplified. In terms of usefulness as a pharmaceutical and agrochemical synthesis intermediate and functional material, trifluoromethyl group, perfluoroethyl group, perfluoropropyl group, perfluoroisopropyl group, perfluorobutyl group, perfluoroisobutyl group, perfluoro-sec- A butyl group, a perfluoro-tert-butyl group or a perfluorohexyl group is desirable, and a trifluoromethyl group is more desirable.

  In the general formula (2), specific examples of X include a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. An iodine atom or a bromine atom is desirable in terms of a good yield, and an iodine atom is more desirable.

On the other hand, in the quinolines represented by the general formula (3), as an amino group which may be substituted by one or two alkyl groups having 1 to 4 carbon atoms represented by R ² , specifically, Amino group, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, sec-butylamino group, dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, Examples thereof include a dibutylamino group, a diisobutylamino group, a di-sec-butylamino group, an ethylmethylamino group, a methylpropylamino group, and a butylmethylamino group.
In addition, R ^{2 in the} general formula (3) and R ^{2a in the} general formula (5) are preferably a hydroxyl group or an amino group in terms of being useful as a pharmaceutical and agrochemical synthesis intermediate and a functional material.

  The molar ratio of the above quinolines and perfluoroalkyl halides is preferably 1: 1 to 1: 100, and more preferably 1: 1.5 to 1:10 in terms of good yield.

Next, the production method of the present invention will be described in detail.
In the reaction of the present invention, the sulfoxides may be used as a solvent as they are. Further, other solvents may be used depending on the solubility of the quinolines, peroxides, iron compounds, perfluoroalkyl halides and acids in these sulfoxides. Solvents that can be used are, for example, water, N, N-dimethylformamide, acetic acid, trifluoroacetic acid, tetrahydrofuran, diethyl ether, ethyl acetate, acetone, 1,4-dioxane, tert-butyl alcohol, ethanol, methanol, isopropyl. Examples thereof include alcohol, trifluoroethanol, hexamethylphosphoric triamide, N-methyl-2-pyrrolidone, N, N, N ′, N′-tetramethylurea and N, N′-dimethylpropyleneurea. These may be used in combination. In view of a good yield, it is desirable to use water, the above sulfoxides, or a mixed solvent of water and sulfoxides.

The reaction temperature can be appropriately selected from the range of 0 ° C to 120 ° C. 20 ° C. or higher is desirable from the viewpoint of good yield, and 100 ° C. or lower is preferable from the viewpoint of suppressing the decomposition of peroxide. Moreover, since this reaction is an exothermic reaction, depending on the scale of the reaction, even if the reaction is started at room temperature, the temperature in the system spontaneously rises to about 40 ° C to about 70 ° C. Even in this temperature range, the target product can be obtained with good yield.
When the reaction is carried out in a closed system, it can be carried out at a pressure appropriately selected from the range of atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction proceeds sufficiently even at atmospheric pressure. The atmosphere during the reaction may be an inert gas such as argon or nitrogen, but proceeds sufficiently even in air.
In addition, when the halogenated perfluoroalkyls are gases at room temperature, they may be used as they are. At that time, it may be diluted with a gas such as argon, nitrogen, air, helium, oxygen or the like to be a mixed gas, and can be used as a gas having a mole fraction of perfluoroalkyl halides of 1 to 100%. When the reaction is carried out in a closed system, perfluoroalkyl halides or a mixed gas can be used as a reaction atmosphere. The pressure at that time can be carried out at a pressure appropriately selected from the range of atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction proceeds sufficiently even at atmospheric pressure. Alternatively, perfluoroalkyl halides or mixed gas may be bubbled and introduced into the reaction solution in an open system. The introduction rate of the halogenated perfluoroalkyls or mixed gas at that time depends on the scale of the reaction, the amount of the reaction reagent, the reaction temperature, and the molar fraction of the halogenated perfluoroalkyls in the mixed gas. The speed selected from the range of 200 mL is sufficient.

  The method for isolating the target product from the solution after the reaction is not particularly limited, but may be a general-purpose method such as solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization or sublimation. The object can be obtained.

  The quinoline having a perfluoroalkyl group of the present invention thus obtained is represented by the above general formula (4), more preferably represented by the following general formula (5).

[Wherein, Rf represents the same content as described above, and R ^2a represents an amino group which may be substituted with one or two alkyl groups having 1 to 4 carbon atoms. ]

EXAMPLES Next, although an Example demonstrates this invention in detail, this invention is not limited to these.
In Examples, ¹ H-NMR and ¹⁹ F-NMR were measured using Bruker Avance 250 (250 MHz and 235 MHz), and ¹³ C-NMR was measured using Bruker Avance 500 (125 MHz). In addition, the Mass spectrum was measured using SHIMAZU GAS CROMATOGRAPH MASS SPECTROMETER GCMS-QP2010 and Waters micromass ZQ.

Example 1
According to the following reaction formula, 5-trifluoromethylquinoline was produced.

In a two-necked flask in an argon stream, 0.12 mL (1.0 mmol) of quinoline, 2.0 mL (28 mmol) of dimethyl sulfoxide, 2.0 mL (1.0 mmol) of a 1N dimethyl sulfoxide solution of sulfuric acid, and trifluoromethyl iodide 3. 0 mL / L dimethyl sulfoxide solution 1.0 mL (3.0 mmol), 30% hydrogen peroxide solution 0.2 mL (2.0 mmol) and 1.0 mol / L iron (II) sulfate aqueous solution 0.3 mL (0.3 mmol) The mixture was sealed and stirred for 20 minutes. The temperature of the reaction system was 40 to 50 ° C. during stirring. Thereafter, the reaction solution was cooled to room temperature. The production of 5-trifluoromethylquinoline (production rate: 9.8%) was confirmed by ¹⁹ F-NMR using 2,2,2-trifluoroethanol as an internal standard substance. Water was added to the reaction solution and neutralized with an aqueous sodium hydrogen carbonate solution, and the target product was extracted into ethyl acetate. The extract was concentrated and purified by column chromatography to give 5-trifluoromethylquinoline as a pale yellow liquid (0.006 g, yield 3.0%).
Note that “mmol” in the parentheses is the amount of mmol in terms of 100%. The same applies to the following.
¹ H-NMR (deuterated DMSO): δ 7.54 (dd, J = 8.6, 4.2 Hz, 1H), 7.76 (dd, J = 8.7, 7.2 Hz, 1H), 7.94 (D, J = 7.2 Hz, 1H), 8.31 (d, J = 8.6 Hz, 1H), 8.51 (d, J = 8.7 Hz, 1H), 9.01 (dd, J = 1.5 Hz, 4.2 Hz, 1 H).
¹⁹ F-NMR (deuterated DMSO): δ-58.3.
MS (m / z): 197 [M] ⁺

Example 2
According to the following reaction formula, a mixture of 8-amino-5,7-bis (trifluoromethyl) quinoline, 8-amino-5-trifluoromethylquinoline, and 8-amino-7-trifluoromethylquinoline was prepared.

In a two-necked flask, 0.14 g (1.0 mmol) of 8-aminoquinoline was weighed, and the inside of the container was replaced with argon. Further, in an argon stream, 2.0 mL (28 mmol) of dimethyl sulfoxide, 2.0 mL (1.0 mmol) of a 1N dimethyl sulfoxide solution of sulfuric acid, 1.0 mL (3 mL) of a 3.0 mol / L dimethyl sulfoxide solution of trifluoromethyl iodide. 0.0 mmol), 0.2% (1.0 mmol) of 30% aqueous hydrogen peroxide and 0.3 mL (0.3 mmol) of a 1.0 mol / L aqueous solution of iron (II) sulfate were added and sealed, followed by stirring for 20 minutes. The temperature of the reaction system was 40 to 50 ° C. during stirring. Thereafter, the reaction solution was cooled to room temperature. ^{According to 19} F-NMR, 8-amino-5,7-bis (trifluoromethyl) quinoline (production rate 52%), 8-amino-5-trifluoromethylquinoline (production rate 18%) and 8-amino-7. -Production of trifluoromethylquinoline (production rate: 8.6%) was confirmed. In the same manner as in Example 1, 8-amino-5,7-bis (trifluoromethyl) quinoline was converted into a white solid (0.14 g, yield 50%), and 8-amino-5-trifluoromethylquinoline was added. Obtained as a white solid (0.03 g, 15% yield) and 8-amino-7-trifluoromethylquinoline as a white solid (0.009 g, 4.5% yield).

8-Amino-5,7-bis (trifluoromethyl) quinoline:
¹ H-NMR (deuterated chloroform): δ 6.99 (br, 2H), 7.83 (dd, J = 8.7, 4.2 Hz, 1H), 7.88 (s, 1H), 8.45 ( ddq, J = 8.7, 1.5 Hz, J _HF = 1.8 Hz, 1H), 8.95 (dd, J = 4.2, 1.5 Hz).
¹³ C-NMR (deuterated chloroform): δ 104.5 (q, J _CF = 31.2 Hz), 111.6 (q, J _CF = 31.2 Hz), 123.9 (sept, J _CF = 5.1 Hz) _{, 125.6 (q, J CF =} 269.1Hz), 125.9,126.0 (q, J CF = 269.2Hz), 126.9,133.4 (q, J CF = 2.4Hz) , 138.8, 147.9, 149.8.
¹⁹ F-NMR (deuterated chloroform): δ-63.0, -59.5.
MS (m / z): 281 [M + H] ⁺

8-Amino-5-trifluoromethylquinoline:
¹ H-NMR (deuterated chloroform): δ 6.34 (br, 2H), 6.95 (dd, J = 8.2 Hz, J _HF = 0.2 Hz, 1H), 7.64 (dd, J = 8. 7, 4.1 Hz, 1 H), 7.72 (dd, J = 8.2, J _HF = 0.5 Hz, 1 H), 8.39 (ddq, J = 8.7, 1.5 Hz, J _HF = 1.8 Hz, 1 H), 8.84 (dd, J = 4.1, 1.5 Hz).
¹³ C-NMR (deuterated chloroform): δ 106.7, 111.6 (q, J _CF = 30.5 Hz), 123.8, 126.0, 126.4 (q, J _CF = 268.9 Hz), 128 _{.0 (q, J CF = 5.8Hz} ), 132.8 (q, J CF = 2.3Hz), 138.3,148.5,150.2.
¹⁹ F-NMR (deuterated chloroform): δ-58.5.
MS (m / z): 213 [M + H] ⁺

8-Amino-7-trifluoromethylquinoline:
¹ H-NMR (heavy acetone): δ 6.17 (br, 2H), 7.06 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 1H), 7. 49 (dd, J = 8.4 Hz, 4.3 Hz, 1H), 8.14 (dd, J = 8.4 Hz, 1.5 Hz, 1H), 8.71 (dd, J = 4.3 Hz, 1.H). 5 Hz).
¹⁹ F-NMR (heavy acetone): δ-62.3.
MS (m / z): 212 [M] ⁺

Example 3
In a two-necked flask, 0.11 g (0.75 mmol) of 8-aminoquinoline was weighed, and the inside of the container was replaced with argon. Furthermore, in an argon stream, 4.0 mL (56 mmol) of dimethyl sulfoxide, 1.0 mL (3.0 mmol) of a 3.0 mol / L dimethyl sulfoxide solution of trifluoromethyl iodide, 0.2 mL of 30% aqueous hydrogen peroxide (2 0.0 mmol) and 1.0 mL / L iron (II) sulfate aqueous solution 0.3 mL (0.3 mmol) were added and sealed, followed by stirring for 20 minutes. The temperature of the reaction system was 40 to 50 ° C. during stirring. Thereafter, the reaction solution was cooled to room temperature. According to ¹⁹ F-NMR using 2,2,2-trifluoroethanol as an internal standard substance, 8-amino-5,7-bis (trifluoromethyl) quinoline (39% yield), 8-amino-5-trimethyl Production of fluoromethylquinoline (production rate 30%) and 8-amino-7-trifluoromethylquinoline (production rate 15%) was confirmed.

Example 4
In a two-necked flask, 0.11 g (0.75 mmol) of 8-aminoquinoline and 0.056 g (0.3 mmol) of ferrocene were weighed, and the inside of the container was replaced with argon. Further, in an argon stream, 2.0 mL (28 mmol) of dimethyl sulfoxide, 2.0 mL (1.0 mmol) of a 1N dimethyl sulfoxide solution of sulfuric acid, 1.0 mL (3 mL) of a 3.0 mol / L dimethyl sulfoxide solution of trifluoromethyl iodide. 0.0 mmol) and 0.2 mL (2.0 mmol) of 30% aqueous hydrogen peroxide were added and sealed, followed by stirring for 20 minutes. The temperature of the reaction system was 40 to 50 ° C. during stirring. Thereafter, the reaction solution was cooled to room temperature. By ¹⁹ F-NMR using 2,2,2-trifluoroethanol as an internal standard substance, 8-amino-5,7-bis (trifluoromethyl) quinoline (production rate: 37%), 8-amino-5-trimethyl Production of fluoromethylquinoline (production rate 28%) and 8-amino-7-trifluoromethylquinoline (production rate 15%) was confirmed.

Example 5
In a two-necked flask, 0.11 g (0.75 mmol) of 8-aminoquinoline and 0.056 g (0.3 mmol) of ferrocene were weighed, and the inside of the container was replaced with argon. Further, in an argon stream, 4.0 mL (56 mmol) of dimethyl sulfoxide, 1.0 mL (3.0 mmol) of a 3.0 mol / L dimethyl sulfoxide solution of trifluoromethyl iodide and 0.2 mL of 30% hydrogen peroxide (2 0.0 mmol) was added, sealed and stirred for 20 minutes. The temperature of the reaction system was 40 to 50 ° C. during stirring. Thereafter, the reaction solution was cooled to room temperature. According to ¹⁹ F-NMR using 2,2,2-trifluoroethanol as an internal standard substance, 8-amino-5,7-bis (trifluoromethyl) quinoline (production rate: 32%), 8-amino-5-trimethyl Production of fluoromethylquinoline (production rate 40%) and 8-amino-7-trifluoromethylquinoline (production rate 20%) was confirmed.

  The method for producing a quinoline having a perfluoroalkyl group according to the present invention is simple and efficient, and the quinoline can be produced. The obtained quinoline includes an intermediate for pharmaceutical / pesticidal synthesis, an organic nonlinear optical material, It is useful as a light emitting material.

Claims (14)

General formula (1)
[Wherein, R ^1a and R ^1b represent an alkyl group having 1 to 12 carbon atoms or an optionally substituted phenyl group. ]
In the presence of sulfoxides, peroxides, iron compounds, and optionally acids,
General formula (2)
[Wherein, Rf represents a perfluoroalkyl group having 1 to 6 carbon atoms, and X represents a halogen atom. ]
Perfluoroalkyl halides represented by:
General formula (3)


[Wherein, R ² represents a hydrogen atom, a hydroxyl group, or an amino group which may be substituted with one or two alkyl groups having 1 to 4 carbon atoms. ]
With a quinoline represented by
General formula (4)
Wherein, Rf and ^{R 2} represents the same content as the, n represents 1 or 2. ]
A method for producing a quinoline having a perfluoroalkyl group, comprising obtaining a quinoline having a perfluoroalkyl group represented by the formula: The molar ratio of the quinoline represented by the general formula (3) and the sulfoxide is 1: 1 to 1: 200, the molar ratio of the quinoline to peroxide is 1: 0.1 to 1:10, The molar ratio of the quinoline to the iron compound is 1: 0.01 to 1:10, the molar ratio of the quinoline to the acid to be added is 1: 0.001 to 1: 5, and the quinoline and the halogenated compound. The manufacturing method of the quinoline which has the perfluoroalkyl group of Claim 1 whose molar ratio with perfluoroalkyl is 1: 1-1: 100. The quinoline having a perfluoroalkyl group according to claim 1 or 2 , wherein the sulfoxide represented by the general formula (1) is at least one selected from the group of dimethyl sulfoxide, dibutyl sulfoxide and diphenyl sulfoxide. Method. The perfluoro according to any one of claims 1 to 3, wherein the peroxide is at least one selected from the group consisting of hydrogen peroxide or an aqueous solution thereof, hydrogen peroxide-urea complex, tert-butyl peroxide and peracetic acid. A method for producing quinolines having an alkyl group. The method for producing a quinoline having a perfluoroalkyl group according to claim 4 , wherein the peroxide is hydrogen peroxide or an aqueous solution thereof. The iron compound is iron (II) sulfate, iron (II) sulfate, iron (II) tetrafluoroborate, iron (II) chloride, iron (II) bromide, iron (II) iodide, iron acetate (II) ), iron oxalate (II), bis acetylacetonato iron (II), ferrocene, bis (eta ⁵ - claim 1 is at least one selected from the group consisting of pentamethylcyclopentadienyl) iron and iron powder A method for producing a quinoline having a perfluoroalkyl group according to any one of -5 .   6. The method for producing a quinoline having a perfluoroalkyl group according to claim 5, wherein the iron compound is iron (II) sulfate or ferrocene. Acid is sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, phosphoric acid, hexafluorophosphoric acid, tetrafluoroboric acid, formic acid, acetic acid, propionic acid, oxalic acid, p-toluenesulfonic acid, trifluoromethane The method for producing a quinoline having a perfluoroalkyl group according to any one of claims 1 to 7 , which is at least one selected from the group of sulfonic acid and trifluoroacetic acid. The method for producing a quinoline having a perfluoroalkyl group according to claim 8 , wherein the acid is sulfuric acid. The method for producing a quinoline having a perfluoroalkyl group according to any one of claims 1 to 9 , wherein Rf in the general formula (2) is a trifluoromethyl group or a perfluoroethyl group. X of general formula (2) is an iodine or a bromine, The manufacturing method of the quinoline which has a perfluoroalkyl group in any one of Claims 1-10 . The method for producing a quinoline having a perfluoroalkyl group according to any one of claims 1 to 11 , wherein the reaction temperature is in the range of 20 ° C to 100 ° C.   The method for producing a quinoline having a perfluoroalkyl group according to any one of claims 1 to 12, wherein the reaction pressure is from atmospheric pressure (0.1 MPa) to 1.0 MPa. General formula (5)
[Wherein, Rf represents the same content as described above, and R ^2a represents an amino group which may be substituted with one or two alkyl groups having 1 to 4 carbon atoms. ]
The quinoline which has a perfluoroalkyl group obtained by the manufacturing method of the quinoline which has a perfluoroalkyl group in any one of Claims 1-13 represented by these.