TWI829792B - Method for producing fluorinated aromatic secondary or tertiary amine compounds - Google Patents

Abstract

A method for manufacturing a fluorinated aromatic second-level or third-level amine compound, which is characterized in that the fluorinated aromatic first-level amine compound is mixed with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon. The step of reacting in the presence of a catalyst, a ligand and a base. The catalyst contains divalent palladium acetate, and the ligand contains tri-tert-butylphosphine or tri-tert-butylphosphonium borate compound. This method may not A special catalyst is used to couple fluorinated aromatic compounds with chlorinated, brominated or iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons to simply and effectively produce the second compound having a fluoroaryl group in the molecule. or tertiary amine compounds.

Description

Method for producing fluorinated aromatic secondary or tertiary amine compounds

The present invention relates to a method for producing fluorinated aromatic secondary or tertiary amine compounds.

The reaction of coupling amines with halides or pseudohalides to form C-N bonds using palladium catalysts can be used to synthesize aromatic amines or form heterocycles. This coupling is an important technology in many fields such as medicine and materials (Non-Patent Document 1), and research on the catalysts used in this reaction or the reaction process has been extensively carried out.

On the other hand, since fluorine has the highest electronegativity among all elements, it not only has the characteristic of greatly changing the electronic state of the entire molecule by introducing it into the molecule, but also has the same atomic radius as the hydrogen atom. Introducing fluorine atoms into the molecule instead of hydrogen atoms has the characteristic of suppressing changes in molecular size compared to the case of introducing other atoms or substituents. Therefore, research on fluoride is extremely popular, and there have been many reports on fluoride used in medicine or electronic materials. For example, in the field of electronic materials, it has been reported that an amine compound having a fluorine atom in the molecule is suitable as a charge-transporting substance (Patent Document 1).

Under these circumstances, as a synthesis method of a fluoroaryl compound having an amine group, the reaction of an aromatic amine and a perfluoroarylboronic acid using copper acetate as a catalyst (Non-Patent Document 2), and the reaction of lithium hydroxide with lithium hydroxide have been reported. The reaction of aniline and perfluorobenzene in the presence of t-BuONa (Non-Patent Document 3), the reaction of aniline and perfluorobenzene in the presence of t-BuONa (Non-Patent Document 4), etc., but these reactions are all at the reaction site The amine group exists on the side of the aromatic compound that does not have a fluorine atom among the two raw materials used in the coupling reaction.

There are few reported examples of the coupling reaction between fluoroarylamine compounds having fluorine atoms and amine groups and haloaryl compounds. For example, in Non-Patent Document 5, it has been reported that a special palladium carbene complex is used as a catalyst, so that This is a method of coupling fluoroarylamine compounds and haloaryl compounds, but the catalyst is expensive and the yield of the target product is low. In addition, the arylation system reactivity of fluoroarylamine compounds is generally low, and there are no reports of derivatization into third-order amine compounds. [Prior technical literature] [Patent Document]

[Patent Document 1] International Publication No. 2008/032617 [Non-patent literature]

[Non-patent document 1] Chem. Rev. 2016, 116, 12564-12649 [Non-patent document 2] Angew. Chem. Int. Ed. 2014, 53, 3223 [Non-patent document 3] Journal of Fluorine Chemistry, 74(2), 177-9; 1995 [Non-patent document 4] RSC Advances, 5(10), 7035-7048; 2015 [Non-patent document 5] Angew. Chem. Int. Ed. 2014, 53, 3223

[Problem to be solved by the invention]

The present invention was completed in view of the above situation, and its object is to provide a coupling reaction between a fluorinated aromatic amine compound and a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon without using a special catalyst. It is a simple and efficient method for producing a second- or third-level amine compound having a fluoroaryl moiety in the molecule. [Means used to solve problems]

In order to achieve the above purpose, the inventor has repeatedly conducted active reviews and found that in the presence of a specific palladium catalyst, a specific ligand and a base, the amine group of the fluorinated aromatic amine compound can be combined with the chlorinated, brominated or iodinated aromatic compound. The chlorine atom, bromine atom, iodine atom or pseudohalogen group of hydrocarbons or pseudo-halogenated aromatic hydrocarbons can be coupled efficiently, and the second or third level of the fluoroaryl site in the molecule can be obtained selectively and efficiently. Tertiary amine compound, thus completing the present invention.

That is, the present invention provides 1. A method for producing a fluorinated aromatic second-level or third-level amine compound, which is characterized in that the fluorinated aromatic first-level amine compound is mixed with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudohalogenated aromatic hydrocarbon. A method for producing a fluorinated aromatic secondary or tertiary amine compound in which a hydrocarbon is reacted in the presence of a catalyst, a ligand and a base, and is characterized by: The aforementioned catalyst contains divalent palladium acetate, The aforementioned ligand includes tri-tert-butylphosphine or tri-tert-butylphosphonium borate compound. 2. The method for producing the fluorinated aromatic second or third amine compound as in 1, wherein the aforementioned tri-tert-butylphosphonium borate compound is tri-tert-butylphosphonium tetrafluoroborate. 3. The method for producing a fluorinated aromatic second- or third-level amine compound as in 1 or 2, wherein the aforementioned fluorinated aromatic first-level amine compound is a fluorinated aromatic third-level amine compound having two or more fluorine atoms in the molecule. Primary monoamine compound or diamine compound. 4. The method for producing a fluorinated aromatic secondary or tertiary amine compound according to any one of 1 to 3, wherein the aforementioned chlorinated, brominated or iodinated aromatic hydrocarbons are mono- or dichloro aromatic hydrocarbons, Mono- or dibromoaromatic hydrocarbons, or mono- or diiodoaromatic hydrocarbons. [Effects of the invention]

According to the manufacturing method of the fluorinated aromatic second-level or third-level amine compound of the present invention, commercially available palladium catalysts and ligands are used to self-fluoride the aromatic first-level amine compound with chlorination, bromination or Iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons can be used to produce second- or third-level fluorinated aromatic amine compounds (fluorine-containing aniline derivatives) with fluoroaryl sites in the molecule efficiently, in high yields, and cheaply. things). According to the production method of the present invention, as will be described in detail later, by changing the reaction ratio of chlorinated, brominated or iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons relative to the fluorinated aromatic primary amine compound, it can be easily The second-stage fluorinated aromatic amine compound and the third-stage fluorinated aromatic amine compound are respectively produced. Furthermore, in this reaction, by polymerizing a fluorinated aromatic primary amine compound and any bifunctional compound of a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudohalogenated aromatic hydrocarbon, it is possible to effectively To produce polymers of oligoaniline derivatives or polyaniline derivatives having a fluoroaryl moiety in the molecule. The fluorine-containing amine compounds such as fluorine-containing aniline derivatives and polymers obtained by the production method of the present invention have excellent transparency because they have fluorine atoms in the molecules, and they exhibit charge transport properties, so they can be used alone or together with other charge transport properties. The combination of materials or doping substances can be suitably used as a material for forming a charge-transporting thin film for electronic devices represented by organic EL devices.

Hereinafter, the present invention will be described in further detail. The method for producing the fluorinated aromatic second-level or third-level amine compound of the present invention is to combine the fluorinated aromatic first-level amine compound with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon. The step of reacting in the presence of a catalyst, a ligand and a base is characterized by using a catalyst system containing divalent palladium acetate, and a ligand system containing tri-tertiary butylphosphine or tri-tertiary phosphine. Butylphosphonium borate compound.

(1) Catalyst The catalyst used in the present invention is one containing divalent palladium acetate (Pd(OAc) ₂ ) as described above, but it is preferred to use divalent palladium acetate alone. The amount of divalent palladium acetate used is not particularly limited as long as it is an amount that can carry out the intended coupling reaction, but it is preferably calculated as palladium metal based on 1 mol of NH at the amine site of the fluorinated aromatic primary amine compound. It is 0.0001~0.2mol, more preferably 0.0003~0.15mol, still more preferably 0.0005~0.1mol, still more preferably 0.001~0.075mol.

Furthermore, in the present invention, other metal catalysts may be used together with divalent palladium acetate within the scope that does not impair the effects of the present invention. Examples of other metal catalysts include copper catalysts such as copper chloride, copper bromide, copper iodide, etc.; Pd(PPh ₃ ) ₄ (tetrakis (triphenylphosphine) palladium), Pd(PPh ₃ ) ₂ Cl ₂ ( Palladium catalysts such as bis(triphenylphosphine)dichloropalladium), Pd(Pt-Bu ₃ ) ₂ (bis(tris(tert-butylphosphine))palladium), etc. When using these other metal catalysts, the usage amount cannot be uniformly specified, but it usually does not reach 100 mol% relative to the divalent palladium acetate.

(2) Coordinator The ligand used in the present invention includes tri-tert-butylphosphine (abbreviated as tBu ₃ P) or tri-tert-butylphosphonium borate compound as mentioned above. The tri-tert-butylphosphonium borate compound is not particularly limited if it is composed of tri-tert-butylphosphonium cation and borate anion. Preferably, the borate anion includes a fluorine-containing borate anion. A specific example of the tri-tert-butylphosphonium borate compound is tri-tert-butylphosphonium tetrafluoroborate compound (hereinafter abbreviated as tBu ₃ PHBF ₄ ), but it is not limited thereto. The usage amount of tBu ₃ P or tri-tert-butylphosphonium borate compound is preferably 0.5 to 6.0 equivalents, more preferably 2.0 to 4.0 equivalents relative to the catalyst used. Especially when the equivalent is less than 0.5, there is a possibility of producing palladium black.

In the present invention, other ligands can also be used together with tBu ₃ P or tri-tert-butylphosphonium borate compound within the scope that does not impair the effect of the present invention, but it is preferred to use tBu ₃ P alone or alone. Tri-tert-butylphosphonium borate compound. In particular, fluorinated aromatic primary amine compounds are not dependent on the type of raw materials. They not only enable coupling reactions with good reproducibility, but are also stable solids in the atmosphere and are easy to handle. Therefore, tBu ₃ PHBF ₄ is preferably used. , preferably used alone. Specific examples of other ligands include triphenylphosphine, tri-o-tolylphosphine, diphenylmethylphosphine, phenyldimethylphosphine, trimethylphosphine, triethylphosphine, and tributylphosphine , di-tert-butyl(phenyl)phosphine, di-tert-butyl(4-dimethylaminophenyl)phosphine, 1,2-bis(diphenylphosphino)ethane, 1,3- Bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-bis(diphenylphosphino)ferrocene and other tertiary phosphines; triphosphite Level 3 phosphites such as methyl ester, triethyl phosphite, triphenyl phosphite, etc. When using other ligands, the usage amount cannot be specified uniformly, but it is usually less than 100 mol% relative to the mass of tBu ₃ P or tri-tert-butylphosphonium borate compound.

(3) Fluorinated aromatic primary amine compounds The production method of the present invention is characterized by the above-mentioned catalyst and ligand, so the fluorinated aromatic primary amine compound used as a raw material for the coupling reaction is not particularly limited. The fluorinated aromatic primary amine compound may be a monoamine compound or a diamine compound, and examples thereof include those represented by the following formulas (X1) and (X2).

(In the formula, Ar ^F1 represents a fluorinated aryl group, and Ar ^F2 represents a fluorinated aryl group).

The fluorinated aryl group only needs to have at least one hydrogen atom of the aryl group substituted with a fluorine atom, but preferably two or more hydrogen atoms are substituted with a fluorine atom. The fluorinated aryl group only needs to have at least one hydrogen atom of the aryl group substituted with a fluorine atom, but preferably two or more hydrogen atoms are substituted with a fluorine atom. That is, the fluorinated aromatic primary amine compound used in the present invention is preferably a fluorinated aromatic primary monoamine compound or diamine compound having two or more fluorine atoms in the molecule.

The aryl group is preferably an aryl group having 6 to 20 carbon atoms. Specific examples thereof include phenyl; 1-naphthyl, 2-naphthyl, 1-anthracenyl, 2-anthracenyl, and 9-anthracenyl. , 1-phenanthrenyl, 2-phenanthrenyl, 3-phenanthrenyl, 4-phenanthrenyl, 9-phenanthrenyl, 1-condensed tetraphenyl (naphthacenyl), 2-condensed tetraphenyl, 5-condensed tetraphenyl, The derived group is derived by removing one hydrogen atom on the aromatic ring of aromatic hydrocarbon compounds such as 2-pyrenyl, 1-pyrenyl, 2-pyrenyl, pentabiphenyl, benzopyrenyl, triphenyl, etc. ;Biphenyl-2-yl, biphenyl-3-yl, biphenyl-4-yl, p-terphenyl-4-yl, m-terphenyl-4-yl, o-terphenyl-4-yl, 1,1' -Binaphth-2-yl, 2,2'-binaphth-1-yl, and other ring-linked aromatic hydrocarbon compounds are derived groups by removing one hydrogen atom on the aromatic ring. The aryl group is preferably an aryl group having 6 to 20 carbon atoms. Specific examples thereof include 1,2-phenylene group, 1,3-phenylene group, and 1,4-phenylene group; 1, 5-naphthalenediyl, 1,8-naphthalenediyl, 2,6-naphthalenediyl, 2,7-naphthalenediyl, 1,2-anthracenediyl, 1,3-anthracenediyl, 1,4- Anthracenediyl, 1,5-anthracenediyl, 1,6-anthracenediyl, 1,7-anthracenediyl, 1,8-anthracenediyl, 2,3-anthracenediyl, 2,6-anthracenediyl Remove two hydrogen atoms on the aromatic ring of condensed ring aromatic hydrocarbon compounds such as 2,7-anthracenediyl, 2,9-anthracenediyl, 2,10-anthracenediyl, 9,10-anthracenediyl, etc. Derivatized groups; biphenyl-4,4'-diyl, p-terphenyl-4,4"-diyl and other ring-linked aromatic hydrocarbon compounds have two derived groups by removing the hydrogen atoms on the aromatic ring. wait.

Specific examples of the fluorinated aromatic primary amine compound preferably used in the present invention include 2-fluoroaniline, 3-fluoroaniline, 4-fluoroaniline, 2,6-difluoroaniline, 2,4,6 -Trifluoroaniline, pentafluoroaniline, etc., but are not limited thereto.

(4) Chlorinated, brominated or iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons As a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon, it can be a monochlorine, monobromo or monoiodo or mono-pseudo-halogen compound having one and a fluorinated aromatic first stage. The compound at the reaction site of the amine group reaction of the amine can also be a reaction site such as dichloride, dibromide or diiodo, or a dipseudohalogen compound with more than two amine groups reacting with the fluorinated aromatic primary amine. Examples of compounds of the moiety include those represented by the following formulas (Y1) and (Y2).

(In the formula, Ar ¹ represents an aryl group, Ar ² represents an aryl group, and X independently represents a chlorine atom, a bromine atom, an iodine atom or a pseudohalogen group).

Examples of the aryl group and aryl group are the same as those described above. Examples of the pseudohalogen group include (fluoro)alkylsulfonyloxy, trifluoromethanesulfonyloxy, nonafluorobutanesulfonyloxy, etc.; benzenesulfonyloxy, toluenesulfonyloxy, etc. Aromatic sulfonyloxy groups, etc. As X, from the viewpoint of reactivity, a bromine atom or an iodine atom is preferred.

In particular, the chlorinated, brominated or iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons used in the present invention are preferably mono or dichloro aromatic hydrocarbons, mono or dibromo aromatic hydrocarbons, or mono or diiodo aromatic hydrocarbons. Hydrocarbons, more preferably mono- or dibromoaromatic hydrocarbons, or mono- or diiodoaromatic hydrocarbons.

Specific examples of chlorinated, brominated or iodinated aromatic hydrocarbons or pseudo-halogenated aromatic hydrocarbons that can be preferably used in the present invention include chlorobenzene, bromobenzene, iodobenzene, 4-chloroanisole, 4 - Bromoanisole, 4-iodoanisole, etc., but are not limited to these.

(5)Alkali The base used in this reaction is not particularly limited, and examples include lithium, sodium, potassium, lithium hydride, sodium hydride, lithium hydroxide, potassium hydroxide, lithium tert-butoxide, sodium tert-butoxide, Third alkali metal monomers such as potassium butyrate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, alkali metal hydride, alkali metal hydroxide, alkali metal alkoxide, carbonic acid Alkali metals, alkali metal bicarbonates; alkaline earth metal carbonates such as calcium carbonate; n-butyllithium, 2nd-butyllithium, 3rd-butyllithium, lithium diisopropylamide (LDA), 2,2,6, 6-Lithium tetramethylpiperidine (LiTMP), lithium hexamethyldisilazane (LHMDS) and other organic lithiums; triethylamine, diisopropylethylamine, tetramethylethylenediamine, triethylenediamine Amine, pyridine, etc., but preferably is a secondary amine such as LDA, LiTMP, LHMDS, etc. Lithium amide reagent through lithiation or an alkali metal alkoxide such as tertiary butoxylithium.

(6) Coupling reaction In the manufacturing method of the present invention, when obtaining the second-level fluorinated aromatic amine, the fluorinated aromatic first-level amine compound is combined with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon. The feeding ratio of hydrocarbons is preferably about 1.0 to 1.2 mol of the reaction site of the chlorine, bromine, iodine or pseudohalogen group of the aromatic hydrocarbon relative to 1 mol of the NH ₂ group of the fluorinated aromatic primary amine compound. For example, based on the substance mass (mol) ratio, in the reaction between formula (X1) and formula (Y1), relative to (X1) 1, (Y1) is preferably about 1 to 1.2. In the reaction between formula (X1) and formula (Y1) When reacting (Y2), (Y2) is preferably around 0.5~0.6 relative to (X1) 1. When reacting formula (X2) with formula (Y1), relative to (X2) 1, (Y1) is preferably about 0.5~0.6. Preferably, it is about 2 to 2.4. In the reaction between formula (X2) and formula (Y2), relative to (X2) 1, (Y2) is preferably about 1 to 1.2.

On the other hand, in the production method of the present invention, when obtaining the third-level fluorinated aromatic amine, the fluorinated aromatic first-level amine compound is combined with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon. The feed ratio of the reaction site of the chlorine, bromine or iodine or pseudohalogen group of the aromatic hydrocarbon can be set to 2.0 mol or more relative to 1 mol of the NH ₂ group of the fluorinated aromatic primary amine compound, but it is preferably About 2.0~2.4mol. For example, based on the material mass (mol) ratio, in the reaction between formula (X1) and formula (Y1), relative to (X1) 1, (Y1) is preferably about 2.0~2.4, and in the reaction between formula (X2) and formula (X1) In the reaction of (Y1), (Y1) is preferably about 4.0 to 4.8 relative to (X2) 1.

The coupling reaction of the present invention is performed in a solvent based on the fact that all the raw material compounds are solid or in order to obtain the target fluorinated aromatic second or third amine compound efficiently. When a solvent is used, its type is not particularly limited as long as it does not adversely affect the reaction. Specific examples include aliphatic hydrocarbons (pentane, n-hexane, n-octane, n-decane, decalin, etc.), halogenated aliphatic hydrocarbons (chloroform, dichloromethane, dichloroethane, tetrachloride, etc.). Carbon, etc.), aromatic hydrocarbons (benzene, nitrobenzene, toluene, o-xylene, m-xylene, p-xylene, mesitylene, etc.), halogenated aromatic hydrocarbons (chlorobenzene, bromobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, etc.), ethers (diethyl ether, diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxy ethane, 1,2-diethoxyethane, etc.), ketones (acetone, methyl ethyl ketone, methyl isobutyl ketone, di-n-butyl ketone, cyclohexanone, etc.), amides classes (N,N-dimethylformamide, N,N-dimethylacetamide, etc.), lactams and lactones (N-methylpyrrolidone, γ-butyrolactone, etc.), Urea (N,N-dimethylimidazolidinone, tetramethylurea, etc.), triscenes (dimethyltrisoxide, cyclotenine, etc.), nitriles (acetonitrile, propionitrile, butyronitrile, etc.), etc. , these solvents can be used alone, or two or more types can be mixed and used. In particular, in the present invention, aromatic hydrocarbons are preferably used as solvents, and toluene is more preferably used.

The lower limit of the reaction temperature cannot be determined uniformly because it depends on the reactivity of the reaction substrate, etc. However, if it is 45°C or above, the coupling reaction usually proceeds well. In particular, when considering further improvement of reactivity, the lower limit of the reaction temperature is preferably 60°C or higher, more preferably 75°C or higher, and still more preferably 90°C or higher. On the other hand, the upper limit of the reaction temperature cannot be determined uniformly because it varies depending on the boiling point of the solvent used, but it is usually about 200°C or less. After the reaction is completed, post-treatment is performed according to common methods to obtain the intended fluorinated aromatic second- or third-level amine compound. [Example]

Hereinafter, examples and comparative examples will be given to explain the present invention in more detail. However, the present invention is not limited to the following examples.

[1] Equipment and reagents The physical properties of the sample were measured using the following equipment under the following conditions. (1) Liquid chromatography (reaction tracking) Device: Shimadzu Corporation UV-VIS detector: SPD-20A Column oven: CTO-20A Degassing unit: DGU-20A Liquid delivery unit: LC-20AB Automatic sampling Machine: SIL-20A Column: Poroshell 120 EC-C18 (2.7μm, 3.0×50mm, Agilent) Column temperature: 40℃ Solvent: acetonitrile/water Acetonitrile concentration: 40% (0-0.01min) →40%-100 %(0.01-5min) →100%(5-15min)(volume ratio) Detector: UV (2)NMR: Avance III 500MHz made by Bruker Company Internal standard ¹⁹ F-NMR chemical shift correction trifluorotoluene=-64ppm ¹³ C -NMR chemical shift correction

Acetone-d6=206.68ppm

Chloroform-d1=77.23ppm

N,N-dimethylformamide-d7=163.15ppm

Tetrahydrofuran-d8=67.57ppm

(3)HRMS(ESI)

Device: JMS MStation 700T manufactured by JEOL Corporation

The reagents used in the following Examples and Comparative Examples are as follows.

Pd(OAc) ₂ [Tokyo Chemical Industry Co., Ltd.]

Pd(DBA) ₂ [Tokyo Chemical Industry Co., Ltd.]

t-BuONa [KISHIDA Chemical Co., Ltd.]

tBu ₃ PHBF ₄ [Tokyo Chemical Industry Co., Ltd.]

BINAP [Tokyo Chemical Industry Co., Ltd.]

Tri-n-butylphosphine [Tokyo Chemical Industry Co., Ltd.]

Tri-cyclohexylphosphine 15% toluene solution [Tokyo Chemical Industry Co., Ltd.]

Tri-tert-butylphosphine [Tokyo Chemical Industry Co., Ltd.]

Triphenylphosphine [Tokyo Chemical Industry Co., Ltd.]

2-Fluoroaniline [Tokyo Chemical Industry Co., Ltd.]

3-Fluoroaniline [Tokyo Chemical Industry Co., Ltd.]

4-Fluoroaniline [Tokyo Chemical Industry Co., Ltd.]

2,6-Difluoroaniline [Tokyo Chemical Industry Co., Ltd.]

2,4,6-Trifluoroaniline [Tokyo Chemical Industry Co., Ltd.]

Pentafluoroaniline [Tokyo Chemical Industry Co., Ltd.]

4-Bromoanisole [Tokyo Chemical Industry Co., Ltd.]

4-Bromoanisole [Tokyo Chemical Industry Co., Ltd.]

4,4’-Diaminooctafluorobiphenyl [Tokyo Chemical Industry Co., Ltd.]

Bromobenzene [Tokyo Chemical Industry Co., Ltd.]

4-Bromobiphenyl [Tokyo Chemical Industry Co., Ltd.]

2-Bromo-7-iodofluoride [Manufactured by Tokyo Chemical Industry Co., Ltd.]

(9-Phenyl-9H-carbazol-3-yl)boric acid [Manufactured by Tokyo Chemical Industry Co., Ltd.]

3-Bromo-9-phenylcarbazole [manufactured by Aglaia Co., Ltd.]

3-(4-bromophenyl)-9-phenylcarbazole [manufactured by Aglaia Co., Ltd.]

Toluene [Junsheng Chemical Co., Ltd. or Kanto Chemical Co., Ltd.]

Ethyl acetate [Tokyo Chemical Industry Co., Ltd. or Junsei Chemical Co., Ltd.]

Hexane [Junsheng Chemical Co., Ltd.]

Magnesium sulfate [manufactured by KISHIDA Chemical Co., Ltd.]

[2]Synthesis of raw material compounds [Manufacturing Example 1-1]

In a 100mL reaction flask equipped with a reflux tower, measure Pd(dppf)Cl ₂ 0.45mmol (367.5mg), potassium acetate 45mmol (4416.3mg), 3-bromo-N-phenylcarbazole 15mmol (4833.2mg), Bis(pinacol) diborate 11 mmol (4190.0 mg), and the system was replaced with nitrogen. 150 mL of N,N-dimethylformamide was added thereto, and the mixture was stirred for 5 minutes, and then heated and stirred in a 90°C bath for 3 hours. Furthermore, the reaction was followed by chromatography (TLC) using trace amounts of the reaction mixture taken from the system. After the reaction mixture is cooled to room temperature, the solvent is removed from the cooled reaction mixture under reduced pressure and concentrated. The concentrate and 50 mL of ion-exchange water are put into a separatory funnel and washed. Next, 50 mL of chloroform is added for extraction. The organic layer was recovered from the separatory funnel. Next, the recovered organic layer was dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the obtained filtrate was concentrated. The obtained concentrate was used for column chromatography (developing solvent: hexane/ethyl acetate = 100/0 → 96/4), and the eluate containing the target substance was separated. Finally, the solvent was removed from the separated fraction under reduced pressure to obtain 4.21 g of N-phenylcarbazol-3-ylboronic acid pinacol ester (yield 76%). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 1.41(s, 12H), 7.29 (ddd, J = 7.9, 6.0, 2.0 Hz, 1H), 7.37 (brd, J = 8.2 Hz, 1H), 7.40 ( m, 2H), 7.48 (t, J = 7.5 Hz, 1H), 7.55 (m, 2H), 7.61 (m, 2H), 8.76 (dd, J = 8.2, 1.2 Hz, 2H), 8.18 (d, J = 7.6 Hz, 1H), 8.64 (s, 1H)

[Manufacturing Example 1-2]

In a 50mL reaction flask equipped with a reflux tower, measure Pd(PPh ₃ ) ₄ 0.09mmol (104.1mg), sodium acetate 9mmol (359.9mg), and N-phenylcarbazole-3-ylboronic acid pinacol ester 3mmol. (1107.8 mg), 4-bromo-4'-iodobiphenyl 3.3 mmol (1184.7 mg), and the system was replaced with nitrogen. 13.5 mL of a mixed solvent of tetrahydrofuran and water (2/1 (v/v)) was added thereto, and the mixture was stirred for 5 minutes, and then heated and stirred in a 50°C bath for 5 hours. Furthermore, the reaction was followed by chromatography (TLC) using trace amounts of the reaction mixture taken from the system. After the reaction mixture was cooled to room temperature, the solvent was removed from the cooled reaction mixture under reduced pressure and concentrated. The concentrate and 50 mL of ion-exchange water were put into a separatory funnel and washed. Next, 50 mL of tetrahydrofuran was added for extraction. The organic layer was recovered from the separatory funnel. Next, the recovered organic layer was dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the obtained filtrate was concentrated. The obtained concentrate was used for column chromatography (developing solvent: hexane/ethyl acetate = 100/0 → 96/4), and the eluate containing the target substance was separated. Finally, the solvent was removed from the separated fraction under reduced pressure to obtain 810 mg of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-9-phenylcarbazole (yield 57%) . ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 7.30-7.33 (m, 1H), 7.43 (m, 2H), 7.50 (m, 4H), 7.57-7.70 (m, 9H), 7.79 (d, J = 8.5 Hz, 2H), 8.20 (d, J = 7.9 Hz, 1H), 8.39 (brs, 1H)

[Manufacturing Example 2-1]

After measuring 30 mmol (11.1 g) of 2-bromo-7-iodoquinone and 3 mmol (683.3 mg) of benzyltriethylammonium chloride into a 100 mL reaction flask, add 60 mL of dimethylsulfoxide and stir while replacing it with nitrogen. 10 minutes. After adding 14 g of a 50 mass% aqueous sodium hydroxide solution prepared separately thereto, and stirring for 10 minutes, 72.5 mmol (4.52 g) of methyl iodide was added dropwise, and the mixture was stirred at room temperature overnight. In addition, a small amount of the solution in the flask was taken during the process, and liquid chromatography was used to track the reaction. As the peak area that can be attributed to the raw material decreases, the peak area that can be attributed to the target product increases. At this time, no conspicuous peak corresponding to the by-product was confirmed. The obtained reaction mixture was added to 800 mL of a mixed solvent of methanol and water (3/1 (v/v)), and the precipitated solid was filtered with a membrane filter. Finally, the recovered solid was dried under reduced pressure at 60°C to obtain 6.26g (78.4%) of 2-bromo-7-iodo-9,9-dimethyl-9H-fluoride. The ¹ H-NMR spectrum of the obtained compound is shown in Figure 1.

[Manufacturing Example 2-2]

Measure 5 mmol (1.44g) of (9-phenyl-9H-carbazol-3-yl)boronic acid and 5.25 mmol of 2-bromo-7-iodo-9,9-dimethyl-9H-benzoate into a 100 mL reaction flask. (2.95g), 15 mmol of sodium hydroxide (600mg), 75mL of a mixed solvent of tetrahydrofuran and water (2/1 (v/v)) and 0.15mmol of tetrakis-triphenylphosphine palladium (173.5mg), while replacing with nitrogen After stirring for 10 minutes, the mixture was stirred at 60°C for 5 hours. In addition, a small amount of the solution in the flask was taken during the process, and liquid chromatography was used to track the reaction. As the peak area that can be attributed to the raw material decreases, the peak area that can be attributed to the target product increases. At this time, no conspicuous peak corresponding to the by-product was confirmed. The obtained reaction mixture was added to 400 mL of a mixed solvent of methanol and water (3/1 (v/v)), and the precipitated solid was filtered with a membrane filter. The filtered solid was dried under reduced pressure at 60°C. Furthermore, the dry solid was dissolved in 20 mL of tetrahydrofuran, the resulting solution was added to 200 mL of hexane, the precipitated solid was filtered with a membrane filter, and the filtered solid was dried under reduced pressure at 60°C. Finally, the dry solid was dissolved in 20 mL of tetrahydrofuran, and 200 mL of a mixed solvent of methanol and water (3/1 (v/v)) was added to the resulting solution. The precipitated solid was dried under reduced pressure at 60°C to obtain 2-bromo- 7-(9-phenyl-9H-carbazol-3-yl)-9,9-dimethylbenzoate 1.28g (49.8%). The ¹ H-NMR spectrum of the obtained compound is shown in Figure 2.

[3] Synthesis of fluorinated aromatic secondary amine compounds (1) Reaction of pentafluoroaniline and 4-bromoanisole

[Comparative Example 1-1] In a 30 mL reaction flask equipped with a reflux tower, Pd(OAc) ₂ 0.05 mmol (11.2 mg), t-BuONa 1.2 mmol (115.3 mg), and pentafluoroaniline 1.2 mmol (219.7 mg) were measured. ), the system is replaced with nitrogen. After adding 4 mL of toluene thereto, further adding 0.1 mmol (20.2 mg) of tri-n-butylphosphine and 1 mmol (187.0 mg) of 4-bromoanisole, the mixture was heated and stirred in a 110° C. bath for 5 hours (internal temperature: 92° C.). In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target product was confirmed.

[Comparative Example 1-2] The reaction was carried out in the same manner as in Comparative Example 1-1 except that 187.0 mg (equivalent to 0.1 mmol) of a 15% toluene solution of tricyclohexylphosphine was used instead of tri-n-butylphosphine. In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target product was confirmed.

[Example 1-1] The reaction was carried out in the same manner as in Comparative Example 1-1, except that 0.1 mmol (20.2 mg) of tri-tert-butylphosphine was used instead of tri-n-butylphosphine. In addition, a small amount of the solution in the flask was taken during the process, and liquid chromatography was used to track the reaction. At this time, no conspicuous peak corresponding to the by-product was confirmed. After the reaction mixture was cooled to room temperature, the cooled reaction mixture, 50 mL of saturated ammonium chloride aqueous solution and 30 mL of ethyl acetate were put into a separatory funnel for extraction. The organic layer was left in the separatory funnel and the aqueous layer was recovered. Put 50 mL of saturated brine into a separatory funnel, wash the remaining organic layer, and recover the aqueous layer and organic layer respectively. Then, all the recovered aqueous layers were put into a separatory funnel, 20 mL of ethyl acetate was put into it for extraction, and the organic layer was recovered. All the recovered organic layers were combined and dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the solvent was distilled off from the obtained filtrate using a rotary evaporator. The obtained residue was dissolved in 3 mL of toluene, and the obtained solution was subjected to column chromatography (developing solvent: hexane/ethyl acetate = 100/0 → 97/3), and the fraction containing the target substance was separated. Finally, the solvent was removed from the separated fraction at 80° C. under reduced pressure to obtain 83.9 mg of the target compound (yield 30%). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ= 3.79 (s, 3H), 5.56 (brs, 1H), 6.63 (tt, J = 10.0, 7.1Hz, 1H), 6.84 (d, J = 8.9 Hz, 2H), 6.92 (brd, J = 8.9 Hz, 2H) ¹³ C NMR (125.77 MHz, CDCl ₃ ): δ = 55.8, 96.8, 114.6, 121.1, 124.6, 134.9, 139.4, 146.8, 156.2 ¹⁹ F NMR (470.4 5MHz , CDCl ₃ ): δ = -154.00, -154.08 (m, 2F), -141.49, -141.57 (m, 2F); IR (neat): ν ^~ = 3398 (m), 3083 (w), 2927 (w ), 2845 (w), 1646 (m), 1613 (w), 1526 (s), 1507 (s), 1497 (s), 1456 (s), 1409 (m), 1294 (m), 1261 (m ), 1241 (s), 1172 (s), 1120 (m), 1112 (m), 1077 (m), 1031 (m), 949 (s), 820 (s), 804 (m), 769 (m ), 726 (m), 709 (m), 691 (m) HRMS (ESI): calculated for C ₁₃ H ₉ F ₄ NO (M+H) ⁺ : 271.0620, found 272.0694.

[Example 1-2] In a 30 mL reaction flask equipped with a reflux tower, Pd(OAc) ₂ 0.05 mmol (11.2 mg), tBu ₃ PHBF ₄ 0.1 mmol (29.0 mg), and t-BuONa 1.2 mmol (115.3 mg), pentafluoroaniline 1.2mmol (219.7mg), and the system was replaced with nitrogen. After adding 4 mL of toluene thereto, 1 mmol (187.0 mg) of 4-bromoanisole was further added, and the mixture was heated and stirred in a 110° C. bath for 4 hours (internal temperature: 92° C.). In addition, a small amount of the solution in the flask was taken during the process, and liquid chromatography was used to track the reaction. As the peak area that can be attributed to the raw material decreases, the peak area that can be attributed to the target product increases. At this time, no conspicuous peak corresponding to the by-product was confirmed. After the reaction mixture was cooled to room temperature, the cooled reaction mixture, 50 mL of saturated ammonium chloride aqueous solution and 30 mL of ethyl acetate were put into a separatory funnel for extraction. The organic layer was left in the separatory funnel and the aqueous layer was recovered. Put 50 mL of saturated brine into a separatory funnel, wash the remaining organic layer, and recover the aqueous layer and organic layer respectively. Then, all the recovered aqueous layers were put into a separatory funnel, 20 mL of ethyl acetate was put into it for extraction, and the organic layer was recovered. All the recovered organic layers were combined and dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the solvent was distilled off from the obtained filtrate using a rotary evaporator. The obtained residue was dissolved in 3 mL of toluene, and the obtained solution was subjected to column chromatography (developing solvent: hexane/ethyl acetate = 100/0 → 97/3), and the fraction containing the target substance was separated. Finally, the solvent was removed from the separated fraction at 80° C. under reduced pressure to obtain 202.7 mg of the target compound (yield 70%).

[Comparative Example 1-3] The reaction was carried out in the same manner as in Example 1-2, except that 0.1 mmol (26.2 mg) of triphenylphosphine was used instead of tBu ₃ PHBF ₄ . In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target product was found.

[Comparative Example 1-4] The reaction was carried out in the same manner as in Example 1-2, except that 0.1 mmol (62.2 mg) of BINAP was used instead of tBu ₃ PHBF ₄ . In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target product was found.

[Comparative Example 1-5] In addition to using Pd(DBA) ₂ 0.05mmol (28.8mg) instead of Pd(OAc) ₂ and using triphenylphosphine 0.1mmol (26.2mg) instead of tBu ₃ PHBF ₄ , respectively, The reaction was carried out in the same manner as in Example 1-2. In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target compound was found.

[Comparative Example 1-6] Except that Pd(DBA) ₂ 0.05mmol (28.8mg) was used instead of Pd(OAc) ₂ and BINAP 0.1mmol (62.2mg) was used instead of tBu ₃ PHBF ₄ , the same results were obtained. The same reaction was carried out in Example 1-2. In addition, a trace amount of the solution in the flask was taken during the process and the reaction was followed by liquid chromatography, but no peak corresponding to the target product was found.

The above-mentioned Examples 1-1 to 1-2 and Comparative Examples 1-1 to 1-6 are summarized in Table 1.

(2) Reaction of mono, di, or trifluoroaniline and 4-bromoanisole

[Example 1-3] In a 30 mL reaction flask equipped with a reflux tower, Pd(OAc) ₂ 0.05 mmol (11.2 mg), tBu ₃ PHBF ₄ 0.1 mmol (29.0 mg), and t-BuONa 1.2 mmol (115.3 mg), the system was replaced with nitrogen. 4 mL of toluene was added thereto, followed by 1.2 mmol (133.3 mg) of 2-fluoroaniline and 1 mmol (187.0 mg) of 4-bromoanisole, and the mixture was heated and stirred in a 110° C. bath for 5 hours (internal temperature: 92° C.). In addition, a small amount of the solution in the flask was taken during the process, and liquid chromatography was used to track the reaction. As the peak area that can be attributed to the raw material decreases, the peak area that can be attributed to the target product increases. At this time, no conspicuous peak corresponding to the by-product was confirmed. After the reaction mixture was cooled to room temperature, the cooled reaction mixture, 50 mL of saturated ammonium chloride aqueous solution and 30 mL of ethyl acetate were put into a separatory funnel for extraction. The organic layer was left in the separatory funnel and the aqueous layer was recovered. Put 50 mL of saturated brine into a separatory funnel, wash the remaining organic layer, and recover the aqueous layer and organic layer respectively. Then, all the recovered aqueous layers were put into a separatory funnel, 20 mL of ethyl acetate was put into it for extraction, and the organic layer was recovered. All the recovered organic layers were combined and dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the solvent was distilled off from the obtained filtrate using a rotary evaporator. The obtained residue was dissolved in 3 mL of toluene, and the obtained solution was subjected to column chromatography (developing solvent: hexane/ethyl acetate = 100/0 → 97/3), and the fraction containing the target substance was separated. Finally, the solvent was removed from the separated fraction at 80° C. under reduced pressure to obtain 174.2 mg of the target compound (yield 80%). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 3.84 (s, 3H), 5.68 (brs, 1H), 6.77-6.79 (m, 1H), 6.93 (d, J = 9.0 Hz, 2H), 7.00 ( brt, 1H), 7.07-7.12 (m, 2H); 7.15 (d, J = 9.0 Hz, 2H) ¹³ C NMR (125.77 MHz, CDCl ₃ ): δ = 55.7, 114.9, 115.2, 115.3, 119.1, 123.3, 124.5, 134.1, 134.7, 152.4, 156.1 ¹⁹ F NMR (470.53 MHz, CDCl ₃ ): δ -136.1 (brs); IR (neat)ν ^~ = 3382 (m), 3010 (w), 2938 (w), 2906 (w), 2838 (w), 1617 (m), 1585 (w), 1504 (s), 1477 (m), 1464 (m), 1455 (m), 1442 (m), 1332 (m), 1296 (m), 1288 (m), 1255 (m), 1233 (s), 1222 (s), 1180 (s), 1171 (m), 1109 (m), 1095 (s), 1029 (s), 1008 (m), 925 (w), 917 (w), 886 (w), 838 (m), 821 (s), 757 (m), 742 (s), 707 (m), 696 (w) HRMS ( ESI): calculated value for C ₁₃ H ₁₂ FNO (M+H) ⁺ 217.0903, found value 218.0963.

[Example 1-4] Except that 1.2 mmol (133.3 mg) of 3-fluoroaniline was used instead of 2-fluoroaniline, the reaction and post-treatment were carried out in the same manner as in Example 1-3 to obtain 99.1 mg of the target product (yield 46 %). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 3.79 (s, 3H), 5.57 (brs, 1H), 6.47 (ddd, J = 8.3, 2.3, 0.9 Hz, 1H), 6.56 (dt, J = 11.4 , 2.3 Hz, 1H), 6.59 (ddd, J = 8.3, 2.2, 0.9 Hz, 1H), 6.87 (d, J = 8.9, 6.7 Hz, 2H), 7.07 (dd, J = 8.9, 6.7 Hz, 2H) , 7.11 (td, J = 8.3, 6.7 Hz, 2H) ¹³ C NMR (125.77 MHz, CDCl ₃ ): δ = 55.7, 101.9, 105.9, 111.0, 1145.0, 123.6, 130.6, 134.8, 147.7, 156.2, 164.2 ^19F NMR (470.53 MHz, CDCl ₃ ): δ = -113.7 (ms) IR (neat): ν ^~ = 3361 (m), 3043 (w), 2966(w), 2915 (w), 2839 (w), 1600 (s), 1584 (m), 1526 (m), 1506 (s), 1490 (s), 1465 (m), 1334 (m), 1290 (m), 1251 (m), 1181 (w), 1174 (w), 1168 (w), 1138 (s), 1109 (s), 1072 (w), 827 (m), 755 (m), 742 (s) HRMS (ESI): for C ₁₃ H ₁₂ FNO ( The calculated value of M+H) ⁺ is 217.0903, and the measured value is 218.0969.

[Example 1-5] Except that 1.2 mmol (133.3 mg) of 4-fluoroaniline was used instead of 2-fluoroaniline, the reaction and post-treatment were carried out in the same manner as in Example 1-3 to obtain 57.4 mg of the target product (yield 26 %). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 3.79 (s, 3H), 5.36 (brs, 1H), 6.84-7.25 (m, 8H) ¹³ C NMR (125.77 MHz, CDCl ₃ ): δ = 55.8, 115.0, 116.0, 118.0, 121.4, 136.8, 141.4, 155.3, 157.4 ¹⁹ F NMR (470.45 MHz, CDCl ₃ ): δ =-125.6(s) IR (neat): ν ^~ = 3392 (w), 3037 (w) , 2955 (w), 2934 (w), 2834 (w), 1603 (w), 1590 (w), 1497 (s), 1464 (m), 1442 (m), 1316 (m), 1295 (m) , 1245 (m), 1213 (s), 1179 (m), 1154 (w), 1109 (w), 1098 (w), 1034 (m), 818 (s), 773 (m), 696 (w) HRMS (ESI): calculated for C ₁₃ H ₁₂ FNO (M+H) ⁺ 217.0903, found 218.0965.

[Example 1-6] Except that 1.2 mmol (154.9 mg) of 2,6-difluoroaniline was used instead of 2-fluoroaniline, the reaction and post-treatment were carried out in the same manner as in Example 1-3 to obtain 43.0 mg of the target product ( Yield 18%). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 3.77 (s, 3H), 5.37 (brs, 1H), 6.81 (brs, 4H), 6.91-6.93 (m, 3H) ¹³ C NMR (125.77 MHz, CDCl ₍ ^_ _{_} ^_ w), 2935 (w), 2835 (w), 1623 (w), 1598 (w), 1504 (s), 1456 (m), 1406 (w), 1294 (m), 1233 (s), 1179 ( m), 1111 (w), 1060 (w), 1033 (m), 999 (s), 818 (m), 778 (w), 758 (m), 728 (w), 707 (w), 695 ( w) HRMS (ESI): calculated for C ₁₃ H ₁₁ F ₂ NO (M+H) ⁺ 235.0809, found 236.0867.

[Example 1-7] Except that 1.2 mmol (176.5 mg) of 2,4,6-trifluoroaniline was used instead of pentafluoroaniline, the reaction and post-treatment were carried out in the same manner as in Example 1-2 to obtain 138.8 mg of the target product. (Yield 55%). ¹ H NMR (500.13 MHz, CDCl ₃ ): δ = 3.76 (s, 3H), 5.14 (brs, 1H), 6.72-6.75 (m, 3H), 6.80 (d, J = 9.0 Hz, 2H) ¹³ C NMR (125.77 MHz, CDCl ₃ ): δ = 55.8, 100.9, 114.7, 117.4, 117.9, 137.6, 154.8, 156.7, 157.8 ¹⁹ F NMR (470.45 MHz, CDCl ₃ ): δ = -119.8 (brs), -116.9 (br s ) IR (neat): ν ^~ = 3396 (w), 3083 (w), 2913 (w), 2837 (w), 1636 (w), 1608 (w), 1504 (s), 1442 (m), 1288 (w), 1235 (s), 1173 (m), 1116 (s), 1030 (s), 996 (s), 837 (s), 817 (s) HRMS (ESI): for C ₁₃ H ₁₀ F ₃ NO (M+H) ⁺ calculated value 253.0714, found value 254.0772.

The above Examples 1-3 to 1-7 are summarized in Table 2. In addition, the results of Example 1-2 are also shown in Table 2.

[4] Synthesis of fluorinated aromatic tertiary amine compounds

(1) Reaction of 4,4’-diaminooctafluorobiphenyl and halogenated aryl group

[Example 2-1]

Add 4,4'-diaminooctafluorobiphenyl 0.5mmol (164mg), bromobenzene 2.1mmol (330mg), Pd(OAc) ₂ 0.2mmol (45mg), tBu ₃ PHBF ₄ 0.4mmol ( 166mg), t-BuONa 4mmol (385mg), and the system was replaced with nitrogen. 10 mL of toluene was added and stirred at room temperature for 5 minutes, and then reacted at 100°C for 6 hours.

After the reaction, the reaction solution was cooled to room temperature and filtered with a membrane filter. Add activated carbon to the filtrate and stir for 1 hour, then filter the solution. The resulting filtrate was concentrated. The concentrate was purified by silica gel chromatography (n-hexane/dichloromethane = 3/2), and then dried under reduced pressure to obtain 95.4 mg of the target product as a solid (yield 30.2%). The ¹ H-NMR spectrum of the obtained compound is shown in Figure 3.

[Example 2-2]

Except that 2.1 mmol (490 mg) of 4-bromobiphenyl was used instead of bromobenzene, the reaction and post-treatment were carried out in the same manner as in Example 2-1 to obtain 150.7 mg of the target substance that was solid at room temperature (yield 32.2%) . The ¹ H-NMR spectrum of the obtained compound is shown in Figure 4.

[Example 2-3]

Except that 2.1 mmol (677 mg) of 3-bromo-9-phenylcarbazole was used instead of bromobenzene, the reaction and post-treatment were carried out in the same manner as in Example 2-1 to obtain 236.2 mg (236.2 mg) of the target substance that was solid at room temperature. Yield 36.6%). The ¹ H-NMR spectrum of the obtained compound is shown in Figure 5.

[Example 2-4]

Except that 2.1 mmol (836 mg) of 3-(4-bromophenyl)-9-phenylcarbazole was used instead of bromobenzene, the reaction and post-treatment were carried out in the same manner as in Example 2-1 to obtain a solid at room temperature. The target substance was 311.8 mg (yield 44.6%). The ¹ H-NMR spectrum of the obtained compound is shown in Figure 6.

[Example 2-5]

It was the same as Example 2-1 except that 2.1 mmol (896 mg) of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-9-phenylcarbazole was used instead of bromobenzene. The reaction and post-treatment were carried out to obtain 391.0 mg of the target substance in a solid state at room temperature (yield 41.1%). The ¹ H-NMR spectrum of the obtained compound is shown in Figure 7.

[Example 2-6]

The reaction was carried out in the same manner as in Example 2-1 except that 2.1 mmol (1080 mg) of 2-bromo-7-(9-phenylcarbazol-3-yl)-9,9-dimethylbenzene was used instead of bromobenzene. After post-processing, 535.0 mg (89.2%) of the target substance was obtained as a solid at room temperature. The ¹ H-NMR spectrum of the obtained compound is shown in Figure 8.

The above Examples 2-1 to 2-6 are summarized in Table 3.

[Fig. 1] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-1. [Fig. 2] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-2. [Fig. 3] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-1. [Fig. 4] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-2. [Fig. 5] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-3. [Fig. 6] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-4. [Fig. 7] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-5. [Fig. 8] is a ¹ H-NMR spectrum chart of the compound obtained in Production Example 2-6.

Claims (3)

A method for manufacturing a fluorinated aromatic second-level or third-level amine compound, which is characterized in that the fluorinated aromatic first-level amine compound is mixed with a chlorinated, brominated or iodinated aromatic hydrocarbon or a pseudo-halogenated aromatic hydrocarbon. A method for producing a fluorinated aromatic secondary or tertiary amine compound in the reaction step in the presence of a catalyst, a ligand and a base, characterized in that the aforementioned catalyst contains divalent palladium acetate, and the aforementioned ligand is Tri-tert-butylphosphonium tetrafluoroborate compound, the usage amount of the aforementioned tri-tert-butylphosphonium borate compound is 2.0 to 4.0 equivalents relative to the catalyst used. The method for producing a fluorinated aromatic second- or third-level amine compound as claimed in claim 1, wherein the aforementioned fluorinated aromatic first-level amine compound is a fluorinated aromatic first-level amine compound having two or more fluorine atoms in the molecule. Monoamine compounds or diamine compounds. The method for producing a fluorinated aromatic secondary or tertiary amine compound as claimed in claim 1 or 2, wherein the aforementioned chlorinated, brominated or iodinated aromatic hydrocarbons are mono- or di-chloro aromatic hydrocarbons, mono- or di-brominated aromatic hydrocarbons. Aromatic hydrocarbons, or mono- or diiodo aromatic hydrocarbons.