JPH11322679A - Method for producing bisarylaminofluorene derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for synthesizing with high activity and high selectivity without generating tar-like substances under mild reaction conditions compared to the conventional Ullmann reaction using copper. SOLUTION: In the presence of a base having tri (tertiary butyl) phosphine and a palladium compound as essential components and a base, the following general formula (1): (Wherein, R1 and R2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, X represents chlorine, bromine or iodine, and n represents 0 or 1).
A diarylamine is reacted or an aryl halide is reacted with an aniline derivative.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a bisarylaminofluorene derivative. More specifically, it is a method for producing a bisarylaminofluorene derivative using a catalyst comprising tri (tert-butyl) phosphine and a palladium compound. Bisarylaminofluorene derivatives are compounds useful as dyes, pharmaceutical intermediates, or as charge transport compounds.

[0002]

2. Description of the Related Art A bisarylaminofluorene is synthesized by an Ullmann reaction in which a corresponding 9,9-dialkyl-2-iodofluorene is reacted with a diarylamine in the presence of a stoichiometric amount of copper or a copper compound. Conventionally, a method for performing this is known. For example, Japanese Patent Application Laid-Open No. 5-125
No. 023 and Japanese Patent Application Laid-Open No. 9-258465 report a production method by Ullmann reaction.

[0003]

However, in the Ullmann reaction, a tar-like substance which is difficult to be separated from a target product by an ordinary method is produced (Japanese Unexamined Patent Publication (Kokai) No. 5-125023).
However, there are problems such as the production of a large amount of copper waste and the use of a high temperature for the reaction, which is not a preferable method from the viewpoint of environment and economy.

[0004] The present invention has been made in view of the above-mentioned problems, and has as its object to produce a tar-like substance under mild reaction conditions without causing the formation of tar-like substances, and to achieve high activity and high selectivity, as compared with the conventional Ullmann reaction using copper. The purpose is to provide a method for performing the synthesis.

[0005]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and as a result, by using a catalyst containing tri (tert-butyl) phosphine and a palladium compound as essential components, The present invention solves the problems of the conventional Ullmann reaction, such as the production of tar-like substances, the use of a large amount of copper, and the high-temperature reaction, and found that a bisarylaminofluorene derivative can be synthesized in high yield. It was completed.

That is, the present invention provides a compound represented by the following general formula (1) in the presence of a base having tri (tertiary butyl) phosphine and a palladium compound as essential components and a base:

[0007]

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Wherein R 1 and R 2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, X represents chlorine, bromine or iodine, and n represents 0 or 1. The following general formula (2)

[0009]

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Wherein Ar ₁ and Ar ₂ each independently represent an aryl group. A diarylamine represented by the following general formula (3):

[0011]

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[0012] (wherein, R1 and R2 are each independently hydrogen atom, an alkyl group or a benzyl group, Ar ₁ and A
r ₂ each independently represents an aryl group, and n represents 0 or 1. A) a method for producing a bisarylaminofluorene derivative represented by the following general formula (1) in the presence of a catalyst having tri (tertiarybutyl) phosphine and a palladium compound as essential components and a base:

[0013]

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Wherein R1 and R2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, X represents chlorine, bromine or iodine, and n represents 0 or 1. Aryl halide represented by the following general formula (4) Ar ₁ -X (4) (wherein, Ar ₁ represents an aryl group), and the following general formula (5) Ar ₂ -NH ₂ (5) (Formula Wherein Ar ₂ represents an aryl group.) An aniline derivative represented by the following general formula (3):

[0015]

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[0016] (wherein, R1 and R2 are each independently hydrogen atom, an alkyl group or a benzyl group, Ar ₁ and A
r ₂ each independently represents an aryl group, and n represents 0 or 1. ) Is a method for producing a bisarylaminofluorene derivative represented by the following formula:

Hereinafter, the present invention will be described in more detail.

In the present invention, a palladium compound and tri (tert-butyl) phosphine are indispensable, and both are combined and added to the reaction system as a catalyst. Regarding the method of addition, they may be added individually to the reaction system, or may be prepared in advance and added in the form of a complex.

In the present invention, the palladium compound is not particularly restricted but includes, for example, palladium (II) chloride, palladium (II) bromide, palladium (II) acetate, palladium acetylacetonate (II),
Dichlorobis (benzonitrile) palladium (II),
Dichlorobis (acetonitrile) palladium (II),
Dichlorobis (triphenylphosphine) palladium (II), dichlorotetraamminepalladium (I
I), divalent palladium compounds such as dichloro (cycloocta-1,5-diene) palladium (II), palladium trifluoroacetate (II), tris (dibenzylideneacetone) dipalladium (0), tris (dibenzylideneacetone) Zero-valent palladium compounds such as dipalladium chloroform complex (0) and tetrakis (triphenylphosphine) palladium (0) can be mentioned. Of these, palladium acetate and tris (dibenzylideneacetone) dipalladium (0) are particularly preferred. The amount of the palladium compound used is not particularly limited, but is 0.001 to 20.0 mol% in terms of palladium, more preferably, in terms of palladium, based on the compound represented by the general formula (1). 0.01
１10.0 mol%.

In the present invention, the amount of tri (tert-butyl) phosphine used is not particularly limited, but is suitably 0.5 to 10 moles per mol of the palladium compound, and more preferably, it is preferably 0.5 to 10 mol per mol of the palladium compound. In the range of 0.8 to 5 moles. The compound represented by the general formula (1) used in the present invention is specifically a halofluorene derivative having a halogen at the 2-position or the 7-position. 2 or 7 in halofluorene derivative
The halogen at position 9 can be selected from the group consisting of chlorine, bromine and iodine, and the substituents R1 and R2 at position 9 can be independently selected from the group consisting of hydrogen, alkyl and benzyl.

Specific examples of the halofluorene derivative include 2-bromo-9,9-dimethylfluorene, 2-bromo-9,9-diethylfluorene, 2-bromo-9,
9-dipropylfluorene, 2-bromo-9,9-dihexylfluorene, 2-bromo-9,9-dibenzylfluorene, 2-iodo-9,9-dimethylfluorene,
2-iodo-9,9-diethylfluorene, 2-iodo-9,9-dipropylfluorene, 2-iodo-9,9
-Dihexylfluorene, 2-chloro-9,9-dimethylfluorene, 2-chloro-9,9-diethylfluorene, 2-chloro-9,9-dipropylfluorene, 2-
Chloro-9,9-dibenzylfluorene, 2,7-dibromo-9,9-dimethylfluorene, 2,7-dibromo-9,9-diethylfluorene, 2,7-dibromo-
9,9-dipropylfluorene, 2,7-dibromo-
9,9-dihexylfluorene, 2,7-dibromo-
9,9-dibenzylfluorene, 2,7-diiodo-
9,9-dimethylfluorene, 2,7-diiodo-9,
9-diethylfluorene, 2,7-diiodo-9,9-
Dipropylfluorene, 2,7-diiodo-9,9-dihexylfluorene, 2,7-dichloro-9,9-dimethylfluorene, 2,7-dichloro-9,9-diethylfluorene, 2,7-dichloro-9 , 9-dipropylfluorene, 2,7-dichloro-9,9-dibenzylfluorene, and the like.

The diarylamine represented by the general formula (2) used in the present invention is an unsubstituted or substituted diarylamine. In the case of a substituted diarylamine, it may be a symmetric or asymmetric diarylamine. Specific examples of these diarylamines include diphenylamine, di (p-tolyl) amine, di (m-tolyl) amine, di (o-tolyl) amine, (3,4-dimethylphenyl) phenylamine, bis (3, 4-dimethylphenyl) amine, di (4-chlorophenyl) amine, di (3
-Chlorophenyl) amine, di (2-chlorophenyl)
Amine, (4-methoxyphenyl) phenylamine, di (4-methoxyphenyl) amine, (4-methoxy-2)
-Methylphenyl) phenylamine, bis (4-methoxy-2-methylphenyl) amine and the like. The amount of the diarylamine to be used is usually 0.7 to 0.7 as a molar ratio with respect to the compound represented by the general formula (1).
It is in the range of 3.0, and more preferably in the range of 0.8 to 2.2.

Specific examples of the aryl halide represented by the above general formula (4) used in the present invention include bromobenzene, chlorobenzene, iodobenzene, o-bromotoluene, m-bromotoluene, p-bromotoluene, and o-bromotoluene. -Chlorotoluene, m-chlorotoluene, p-chlorotoluene, o- (t-butyl) bromobenzene, m- (t-butyl) bromobenzene, p- (t
-Butyl) bromobenzene, 5-bromo-o-xylene, 2-bromo-p-xylene, 3-bromo-o-xylene, 4-bromo-o-xylene, 4-bromo-m-xylene, 5-bromo- m-xylene, 2-chloro-m-
Xylene, 2-chloro-p-xylene, 3-chloro-o
-Xylene, 4-chloro-o-xylene, 4-chloro-
m-xylene, 5-chloro-m-xylene, 5-chloro-m-xylene, o-bromobenzaldehyde, m-bromobenzaldehyde, p-bromobenzaldehyde,
o-chlorobenzaldehyde, m-chlorobenzaldehyde, p-chlorobenzaldehyde, o-bromobenzotrifluoride, m-bromobenzotrifluoride, p
-Bromobenzotrifluoride, o-chlorobenzotrifluoride, m-chlorobenzotrifluoride, p-chlorobenzotrifluoride, o-bromoanisole, m
-Bromoanisole, p-bromoanisole, 1-bromo-2,5-dimethoxybenzene, 1-bromo-3,4
-Dimethoxybenzene, 1-bromo-2,3-dimethoxybenzene, 4-bromo-3-methylanisole, 4-
Chloro-3-methylanisole, o-chloroanisole, m-chloroanisole, p-chloroanisole, o
-Iodoanisole, m-iodoanisole, p-iodoanisole, 4-bromo-1,2- (methylenedioxy) benzene, 3-bromo-1,2- (methylenedioxy) benzene, 4-chloro-1, Examples thereof include 2- (methylenedioxy) benzene, 3-chloro-1,2- (methylenedioxy) benzene, 1-bromonaphthalene, 2-bromonaphthalene, 1-chloronaphthalene, and 2-chloronaphthalene. The amount of the aryl halide to be used is generally in the range of 0.7 to 1.4, more preferably 0.8 to 1.2 in terms of molar ratio with respect to the compound represented by the general formula (1). It is.

Specific examples of the aniline derivative represented by the general formula (5) used in the present invention together with the aryl halide represented by the general formula (4) include aniline, o-toluidine, m -Toluidine, p-toluidine, 2,3-dimethylaniline, 3,
4-dimethylaniline, 4,5-dimethylaniline, 2
-Methoxyaniline, 3-methoxyaniline, 4-methoxyaniline, 4-methoxy-o-toluidine, 4-methoxy-m-toluidine and the like. The amount of these aniline derivatives to be used is generally in the range of 0.7 to 1.4, more preferably in the range of 0.8 to 1.2 in molar ratio with respect to the compound represented by the general formula (1). is there.
When the aniline derivative is used as the amine source, the reaction of the aniline derivative with the halofluorene derivative represented by the general formula (1), the reaction of the aryl halide, or the reaction of the aniline derivative and the aryl halide,
Either method of subsequently reacting the halofluorene derivative can be employed without problems.

The base used in the present invention includes:
What is necessary is just to select from the group consisting of an organic base and an inorganic base,
Although not particularly limited, more preferably, sodium hydride, potassium hydride, lithium hydride, sodium amide, potassium amide, lithium amide, potassium carbonate, sodium carbonate, lithium carbonate, rubidium carbonate, cesium carbonate, hydrogen carbonate Potassium, sodium bicarbonate, sodium metal, potassium metal, lithium metal,
Specific examples include methoxy sodium, methoxy potassium, ethoxy sodium, ethoxy potassium, ethoxy lithium, tertiary butoxy lithium, tertiary butoxy sodium, tertiary butoxy potassium, and the like. The amount of these bases to be used is from 0.7 to 0.7 in molar ratio with respect to the compound represented by the above general formula (1).
It is in the range of 3.2, more preferably in the range of 0.9 to 2.4.

The reaction in the present invention is usually carried out in an inert solvent. The solvent that can be used may be any solvent that does not significantly inhibit the present reaction, and is not particularly limited. Examples thereof include aromatic hydrocarbon solvents such as benzene, toluene, and xylene, diethyl ether, tetrahydrofuran,
Examples include ether solvents such as dioxane, acetonitrile, dimethylformamide, dimethylsulfoxide, hexamethylphosphotriamide and the like. More preferred are aromatic hydrocarbon solvents such as benzene, toluene and xylene.

The present invention is carried out under an atmosphere of an inert gas such as nitrogen or argon under normal pressure, but may be carried out under a pressurized condition.

The present invention is carried out at a reaction temperature in the range of 20 ° C. to 300 ° C., more preferably in the range of 50 ° C. to 200 ° C.

The reaction time depends on the reaction conditions and the general formula (1).
May be selected from the range of several minutes to 72 hours, depending on the compound represented by and the palladium compound.

After completion of the reaction, the desired compound can be obtained by treating according to a conventional method.

The bisarylaminofluorene derivative represented by the above general formula (3) which can be produced by the present invention comprises a compound represented by the above general formula (1) and a diarylamine represented by the above general formula (2). The compound is obtained by reacting or reacting the compound represented by the general formula (1), the aryl halide represented by the general formula (4) and the aniline derivative represented by the general formula (5). Although not particularly limited, specific examples include the following.
That is, 2-diphenylamino-9,9-dimethylfluorene, 2-di (p-tolyl) amino-9,9-dimethylfluorene, 2-di (m-tolyl) amino-9,9-dimethylfluorene, Di (p-methoxyphenyl) amino-9,9-dimethylfluorene, 2- {phenyl (p-methoxyphenyl) amino} -9,9-dimethylfluorene, 2- {phenyl (4-methoxy-2-methylphenyl) Amino｝ -9,9-dimethylfluorene,
2-{(4-methoxy-2-methylphenyl) (m-tolyl) amino} -9,9-dimethylfluorene, 2-
{Phenyl (3,4-dimethylphenyl) amino}-
9,9-dimethylfluorene, 2- {phenyl (1-naphthyl) amino} -9,9-dimethylfluorene, 2-
{Phenyl (4-methoxy-2-methylphenyl) amino} -9,9-diethylfluorene, 2- {phenyl (4-methoxy-2-methylphenyl) amino} -9,
9-dibenzylfluorene, 2-di (p-formylphenyl) amino-9,9-dimethylfluorene, 2,7-
Bis (diphenylamino) -9,9-dimethylfluorene, 2,7-bis {di (p-tolyl) amino} -9,9
-Dimethylfluorene, 2,7-bis {di (m-tolyl) amino} -9,9-dimethylfluorene, 2,7-
Bis {di (p-methoxyphenyl) amino} -9,9-
Dimethylfluorene, 2,7-bis {phenyl (p-methoxyphenyl) amino} -9,9-dimethylfluorene, 2,7-bis {phenyl (4-methoxy-2-methylphenyl) amino} -9,9- Dimethylfluorene,
2,7-bisdiphenyl (3,4-dimethylphenyl)
Amino {-9,9-dimethylfluorene, 2,7-bis {phenyl (1-naphthyl) amino} -9,9-dimethylfluorene, 2,7-bis {phenyl (4-methoxy-2-methylphenyl) amino {-9,9-diethylfluorene, 2,7-bis} phenyl (4-methoxy-2
-Methylphenyl) amino} -9,9-dibenzylfluorene, 2,7-bis {di (p-formylphenyl) amino} -9,9-dimethylfluorene, 2,7-bis {phenyl (p-formylphenyl) ) Amino-9,9
-Dimethylfluorene and the like.

[0032]

Industrial Applicability According to the present invention, a bisarylaminofluorene derivative useful as an intermediate of a dye or a drug or as a charge transporting compound can be converted to a conventional copper compound in the presence of a catalyst comprising a palladium compound and tri (tert-butyl) phosphine. As compared with the Ullmann reaction using benzene, it was possible to synthesize with high activity and high selectivity without generating tar-like substances under mild reaction conditions.

[0033]

EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited to these examples. Example 1 A 30-ml three-necked flask equipped with a thermometer, a three-way cock and a stirrer was purged with nitrogen, and palladium acetate (manufactured by Wako Pure Chemical Industries, Ltd., 9.
0 mg, 0.040 mmol, substrate 2-bromo-9,9
0.84 mol% based on dimethylfluorene), 545.0 mg of sodium tert-butoxy (5.6)
7 mmol), 6 ml of o-xylene, 2-bromo-9,
1.306 g of 9-dimethylfluorene (4.78 mmol)
l), 1.048 g of di (p-tolyl) amine (5.06
mmol) and 0.70 ml of a 42.3 mg / mol-xylene solution of tri (tert-butyl) phosphine (manufactured by Kanto Kagaku) (29.6 mg, 0.117 mmol, 2.9 times the molar amount of palladium). Was. Fifteen
After the temperature was raised to 120 ° C. in about one minute, the mixture was stirred at 120 ° C. for 1 hour. Then, after cooling to room temperature, 10 ml of water was added, and the mixture was extracted with diethyl ether. The mixture was concentrated under reduced pressure, and the obtained residue was dissolved in 2 g of acetone.
5 g was added dropwise to precipitate crystals. After filtration and drying,
694 g (4.35 mmol) of 2-di (p-tolyl)
Amino-9,9-dimethylfluorene was obtained. Yield 91
%, GC purity 99.1%.

Gas Chromatography Analysis Conditions Column: OV-1 0.32 mm ID × 60 m Carrier gas: Nitrogen 1.0 ml / min Injection temperature: 300 ° C. Detector temperature: 300 ° C. Column temperature: 60 ° C. (9 minutes) → heated 10 ° C / min → 300 ° C.

Example 2 Using 2,7-dibromo-9,9-dimethylfluorene in place of 2-bromo-9,9-dimethylfluorene, sodium tert-butoxy was converted to 2,7-dibromo-9,9-dimethylsodium. 1. molar ratio to fluorene
3 equivalents of di (p-tolyl) amine are converted to 2,7-dibromo-
The same operation as in Example 1 was repeated except that 2.1 equivalents were used relative to 9,9-dimethylfluorene. as a result,
2,7-bis {di (p-tolyl) amino} -9,9-dimethylfluorene was obtained with a yield of 89%.

Example 3 A 30 ml three-necked flask equipped with a thermometer, a three-way cock and a stirrer was replaced with nitrogen, and tris (dibenzylideneacetone) was used.
Dipalladium (0) (Stremo, 10.5 mg, 0.
0115 mmol, 0.0230 mmol as Pd,
0.3 relative to the substrate 4-bromo-3-methylanisole
2 mol%), 4-bromo-3-methylanisole
444 g (7.18 mmol), 1.078 g (16.53 mmol) of sodium tert-butoxy, m-
771 mg (7.19 mmol) of toluidine, 6 ml of o-xylene, and 0.5 ml (21.2 mg, 0.084 mmol, based on palladium) of a 42.3 mg / ml o-xylene solution of tri (tert-butyl) phosphine (manufactured by Kanto Kagaku) 3.6 times mol). Fifteen
After the temperature was raised to 120 ° C. in about one minute, the mixture was stirred at 120 ° C. for 1 hour. After confirming disappearance of 4-bromo-3-methylanisole by GC, 1.985 g (7.27 mmol) of 2-bromo-9,9-dimethylfluorene and o-xylene 2
ml of the mixture was added. The mixture was further stirred at 120 ° C. for 4 hours. Then, after cooling to room temperature, 10 ml of water was added, and the mixture was extracted with diethyl ether. After concentration under reduced pressure, the obtained residue was dissolved in acetone (3 g), and methanol (20 g) was added dropwise to precipitate crystals. After filtration and drying, 2.560 g
(6.10 mmol) of 2-{(4-methoxy-2-methylphenyl) (m-tolyl) amino} -9,9-dimethylfluorene was obtained. Yield 85%, GC purity 98.7
%.

Claims (2)

[Claims] 1. In the presence of a base having tri (tertiary butyl) phosphine and a palladium compound as essential components and a base, the following general formula (1): (Wherein R 1 and R 2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, X represents chlorine, bromine or iodine, and n represents 0 or 1) and the following general formula: (2) (Wherein, Ar ₁ and Ar ₂ each independently represent an aryl group). A diarylamine represented by the following general formula (3): (Wherein, R1 and R2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, Ar ₁ and Ar ₂ each independently represent an aryl group, and n represents 0 or 1). A method for producing a bisarylaminofluorene derivative. 2. In the presence of a base comprising tri (tertiary butyl) phosphine and a palladium compound as essential components and a base, the following general formula (1): (Wherein, R1 and R2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, X represents chlorine, bromine or iodine, and n represents 0 or 1), and a compound represented by the following general formula: (4) Ar ₁ -X (4) (wherein, Ar ₁ represents an aryl group.) Aryl halide represented by the following general formula (5) Ar ₂ —NH ₂ (5) Wherein ₂ represents an aryl group.) An aniline derivative represented by the following general formula (3): (Wherein, R1 and R2 each independently represent a hydrogen atom, an alkyl group or a benzyl group, Ar ₁ and Ar ₂ each independently represent an aryl group, and n represents 0 or 1). A method for producing a bisarylaminofluorene derivative.