JP5549840B2 - Method for producing tetraaminobenzene derivative and intermediate thereof - Google Patents

Description

  The present invention relates to a method for producing a tetraaminobenzene derivative useful as a synthetic fiber raw material such as polybenzimidazole (PBI), which is known as a high heat resistance and high strength fiber, and an intermediate thereof.

Regarding tetraaminobenzene derivatives, 4-nitro-2,5-difluoroaniline is used as a raw material, an amino group is oxidized with hydrogen peroxide, and then 1,4-difluoro-2,5-dinitrobenzene is reacted with aniline, N, N′-diphenyl-1,4-diamino-2,5-dinitrobenzene was obtained, and the nitro group was further reduced to an amino group to obtain N ¹ , N ⁴ -diphenyl-1,2,4,5-tetra There is a report of producing aminobenzene (for example, see Non-Patent Document 1). However, this method has disadvantages such as that the raw material is expensive, and 90% hydrogen peroxide water must be used for the oxidation reaction of the amino group, which is very dangerous and economical and industrial. Is extremely disadvantageous.

Material Research Society Symposium Proceeding, Vol. 134, p113-140 (1989)

  In view of the above, it has been desired to develop a method for synthesizing a tetraaminobenzene derivative at a low cost and in a high yield and its process. An object of the present invention is to provide a novel method for producing a tetraaminobenzene derivative that is excellent in economic efficiency and can be synthesized in a high yield, and a synthetic intermediate thereof.

  As a result of intensive studies on the above problems, the present inventors have found a novel method for producing a tetraaminobenzene derivative and have completed the present invention.

  The present invention protects the amino group of the dihalogenophenylenediamine represented by the following general formula (1) with a benzyl group, and then dihalogenophenylene represented by the following general formula (2) protected with the benzyl group. A tetraamine represented by the following general formula (4) is reacted with an aromatic amine in the presence of a palladium catalyst and further debenzylated with a tetraaminobenzene represented by the general formula (3). A method for producing aminobenzenes is provided.

［式中、Ｘはハロゲン原子を表す。］

[Wherein X represents a halogen atom. ]

［式中、Ｂｎはベンジル基、Ｘはハロゲン原子を表す。］

[Wherein, Bn represents a benzyl group, and X represents a halogen atom. ]

［式中、Ｂｎはベンジル基、Ａｒ^１，Ａｒ^２は互いに同一でも異なっていてもよく、フェニル基、１−ナフチル基、２−ナフチル基、１−アントラセニル基または２−アントラセニル基を表す。］

[Wherein, Bn may be a benzyl group, Ar ¹ and Ar ² may be the same or different and each represents a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthracenyl group or a 2-anthracenyl group. ]

［式中、Ａｒ^１，Ａｒ^２は互いに同一でも異なっていてもよく、フェニル基、１−ナフチル基、２−ナフチル基、１−アントラセニル基または２−アントラセニル基を表す。］
また、本発明は、上記一般式（２）で表される化合物、上記一般式（３）で表される化合物を提供するものである。

[In formula, Ar < ¹ >, Ar < ² > may mutually be same or different, and represents a phenyl group, 1-naphthyl group, 2-naphthyl group, 1-anthracenyl group, or 2-anthracenyl group. ]
The present invention also provides a compound represented by the general formula (2) and a compound represented by the general formula (3).

  Hereinafter, the present invention will be described in detail.

  The synthesis of the compound represented by the general formula (2) from the compound represented by the general formula (1), which is the reaction of the present invention, will be described. A dihalogenophenylenediamine represented by the general formula (1), a benzylating agent, a basic substance and a solvent are charged into a reactor and reacted at a predetermined temperature for a predetermined time with stirring, thereby being expressed by the general formula (2). Can be obtained. The dihalogenophenylenediamine represented by the general formula (2) in which the amino group is protected with a benzyl group can be easily separated and purified by a usual method such as recrystallization.

  Examples of the benzylating agent used in the present invention include, but are not limited to, benzyl chloride, benzyl bromide, benzyl iodide and the like.

  In the method of the present invention in which these various benzylating agents are reacted with the dihalogenophenylenediamines, the amount of the benzylating agent used is preferably in the range of 4 to 8 times mol with respect to 2,5-dihalogeno-p-phenylenediamine. . When the amount is less than 4 times mol, the raw material dihalogenophenylenediamine remains unreacted, and when the amount is more than 8 times mol, a large amount of benzylating agent remains, which is not efficient.

  Examples of the solvent used in the present invention include methylene chloride, chloroform, benzene, toluene, acetonitrile, tetrahydrofuran, dioxane, dimethylformamide and the like, preferably dimethylformamide, but are not limited thereto.

  The basic substances used include acid acceptors such as triethylamine, pyridine, dimethylaminopyridine, alkali metal carbonates or alkali metal bicarbonates.

  The reaction temperature is in the range of 0 to 100 ° C., preferably 50 to 70 ° C., but is not limited to this range.

  The reaction time cannot be generally specified depending on the raw material dihalogenophenylenediamine, the amount of the base, the reaction temperature, and the like, but can be selected from the range of several minutes to 72 hours.

  The reaction in the present invention can be performed under normal pressure, in an inert gas atmosphere such as nitrogen or argon, or under pressure.

  The synthesis of the compound represented by the general formula (3) from the compound represented by the general formula (2), which is the reaction of the present invention, will be described. By reacting a benzylated dihalogenophenylenediamine represented by the general formula (2) with an aromatic amine in the presence of a base and a palladium catalyst, the compound represented by the general formula (3) can be easily prepared. Can be synthesized. Then, it can be easily separated and purified by ordinary methods such as recrystallization.

The aromatic amine (Ar ¹ —NH ₂ and Ar ² —NH ₂ ) used in the present invention is not particularly limited, but Ar ¹ and Ar ² may be the same or different from each other. An aromatic amine which is a group, 1-naphthyl group, 2-naphthyl group, 1-anthracenyl group or 2-anthracenyl group is preferably used.

  The amount of the aromatic amine used is preferably in the range of 3 to 20 times the molar amount of the benzylated dihalogenophenylenediamine. When the amount is less than 3 moles, the benzylated dihalogenophenylenediamine remains unreacted, and the resulting aromatic secondary amine further reacts with the aryl halide in the reaction system to select the desired product. Cause a decrease in sex. On the other hand, when the amount is more than 20 times, a large amount of aromatic amine remains, which is not efficient, and the post-treatment operation after the reaction is complicated.

  The base used in the present invention may be selected from inorganic bases and / or organic bases, and is not particularly limited, but more preferably sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxy. Alkali metal alkoxides such as lithium-tert-butoxide, sodium-tert-butoxide, potassium-tert-butoxide, etc., and these can be added to the reaction system as they are, or can also be alkali metal, alkali metal hydride or alkali metal hydroxide. What was prepared in situ from alcohol and alcohol may be used for the reaction system. The amount of the base used is preferably 0.5 times mol or more with respect to the hydrogen halide produced by the reaction. If the amount of the base is less than 0.5 mole, the yield of tetraaminobenzenes represented by the general formula (3) may be low. Further, even when a large excess of base is added, the yield of the tetraaminobenzenes represented by the general formula (3) does not change, but the post-treatment operation after the completion of the reaction becomes complicated, and therefore a more preferable base is preferred. The amount is in the range of 1 to 5 moles.

  In addition, the palladium catalyst used in the present invention is not particularly limited. For example, tetravalent palladium compounds such as sodium hexachloropalladium (IV) tetrahydrate and potassium hexachloropalladium (IV). , Palladium (II) chloride, palladium (II) bromide, palladium (II) acetate, palladium (II) acetylacetonate, dichlorobis (benzonitrile) palladium (II), dichlorobis (acetonitrile) palladium (II), dichlorobis (tri Divalent palladium compounds such as phenylphosphine) palladium (II), dichlorotetraamminepalladium (II), dichloro (cycloocta-1,5-diene) palladium (II), palladium (II) trifluoroacetate, tris (diben ) Dipalladium (0), tris (dibenzylideneacetone) dipalladium (0) chloroform complex, tetrakis (triphenylphosphine) palladium (0) 0-valent palladium compounds such as and the like.

  Although the usage-amount of a palladium compound is not specifically limited, It is 0.000001-20 mol% normally in conversion of palladium with respect to 1 mol of dihalogenophenylenediamines represented by the said General formula (2). is there. If the palladium compound is within the above range, a tetraaminobenzene derivative can be synthesized with a high selectivity. However, since the activity is further improved or an expensive palladium compound is used, a more preferable palladium compound is used. The amount used is in the range of 0.0001 to 5 mol% in terms of palladium with respect to 1 mol of dihalogenophenylenediamine.

  Regarding the palladium catalyst used in the present invention, when tertiary phosphine is used in combination as a catalyst ligand, the reaction can be more efficiently advanced. In the present invention, the tertiary phosphine used in combination with the palladium catalyst is not particularly limited. For example, triethylphosphine, tricyclohexylphosphine, triisopropylphosphine, tri-n-butylphosphine, tri-iso- Trialkyl phosphines such as butyl phosphine, tri-sec-butyl phosphine, and tri-tert-butyl phosphine can be used. Tri-tert-butyl phosphine is more preferable because it improves the selectivity of the arylamine derivative. In the present invention, the tertiary phosphine may be used in an amount of usually 0.01 to 10000 times mol of the palladium catalyst. If the amount of tertiary phosphine used is within the above range, the selectivity of the tetraaminobenzene derivative represented by the general formula (3) is not changed, but the activity is further improved or expensive tertiary phosphine is used. Therefore, the more preferable amount of the tertiary phosphine used is in the range of 0.1 to 10 moles relative to the palladium catalyst. In the present invention, a combination of a palladium compound and a tertiary phosphine is usually used as a catalyst. As an addition method, it may be added to the reaction system alone or may be added after preparing in the form of a complex in advance.

  The reaction in the present invention is usually performed in the presence of an inert solvent. The solvent used is not particularly limited as long as it does not significantly inhibit this reaction, and is not limited to aromatic solvents such as benzene, toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, and the like. And ether organic solvents such as acetonitrile, dimethylformamide, dimethyl sulfoxide, hexamethylphosphotriamide and the like. Of these, aromatic organic solvents such as benzene, toluene and xylene are more preferable.

  The reaction in the present invention can be performed under normal pressure, in an inert gas atmosphere such as nitrogen or argon, or under pressure.

  The reaction in the present invention is carried out at a reaction temperature in the range of 20 to 300 ° C, more preferably in the range of 50 to 200 ° C, but is not limited to this range.

  The reaction time in the present invention cannot be generally specified depending on the amount of benzylated dihalogenophenylenediamine, base, palladium catalyst, reaction temperature, etc., but can be selected from a range of several minutes to 72 hours.

  The synthesis of the compound represented by the general formula (4) from the compound represented by the general formula (3), which is the reaction of the present invention, will be described. A tetraaminobenzene derivative represented by the general formula (3), a palladium catalyst, and a solvent are charged into a reactor and reacted at a predetermined temperature for a predetermined time under stirring in a hydrogen atmosphere. After the reaction, the palladium catalyst is removed from the reaction solution. The deaminolated tetraaminobenzene derivative represented by the general formula (4) can be easily separated and purified by an ordinary method such as recrystallization.

  Examples of the solvent used in the present invention include aromatic organic solvents such as benzene, toluene and xylene, and ether organic solvents such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane, preferably tetrahydrofuran. However, it is not limited to these.

  The palladium catalyst used may be a homogeneous catalyst or a heterogeneous catalyst, and is not particularly limited, but a known supported metal catalyst can also be used. Examples of the carrier include diatomaceous earth, silica, alumina, silica / alumina, magnesia, zirconia, titania, and activated carbon, and activated carbon is particularly preferable.

  The amount of the palladium catalyst used varies depending on the reaction conditions, but is 0.1 to 30% by weight, preferably 1 to 5% as a metal-supported catalyst with respect to the tetraaminobenzene derivative represented by the general formula (3). -10 wt% can be used.

  The reaction temperature is in the range of 0 to 100 ° C., preferably 40 to 60 ° C., but is not limited to this range.

  The reaction in the present invention is carried out under normal pressure and hydrogen, but it can also contain an inert gas such as nitrogen or argon, and can also be carried out under pressure.

  The reaction time cannot be generally specified depending on the tetraaminobenzene derivative represented by the general formula (3), the catalyst amount, the reaction temperature, and the like, but can be selected from a range of several hours to 72 hours.

  The tetraaminobenzene derivative represented by the general formula (4) can be liberated as a hydrochloride by reacting with hydrochloric acid after the debenzylation reaction. The hydrochloric acid to be used may be commercially available concentrated hydrochloric acid (37%), and the amount used is 4 times mol or more, preferably 8 times mol or more, relative to the tetraaminobenzene derivative.

  Moreover, the compound represented by the following general formula (2) and the compound represented by the following general formula (3), which are useful intermediates for the synthesis of the tetraaminobenzene derivative represented by the general formula (4), It is included in the present invention.

上記一般式（２）中、Ｘはハロゲン原子を示し、フッ素原子、塩素原子、臭素原子、ヨウ素原子のいずれかである。

In the general formula (2), X represents a halogen atom and is any one of a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

  Furthermore, the specific example of a compound represented by General formula (2) is illustrated below.

上記一般式（３）中、Ａｒ^１，Ａｒ^２は互いに同一でも異なっていてもよく、フェニル基、１−ナフチル基、２−ナフチル基、１−アントラセニル基または２−アントラセニル基である。なお、一般式（３）で表される化合物の好ましい具体例を以下に例示するが、本発明の化合物はこれらに限定されるものではない。

In the general formula (3), Ar ¹ and Ar ² may be the same as or different from each other, and are a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthracenyl group, or a 2-anthracenyl group. In addition, although the preferable specific example of a compound represented by General formula (3) is illustrated below, the compound of this invention is not limited to these.

  By the novel method for producing a tetraaminobenzene derivative according to the present invention, a tetraaminobenzene derivative represented by the general formula (4) can be produced in high yield and economically. In addition, the compound of the present invention is useful as a synthetic intermediate for tetraaminobenzene derivatives.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited only to these Examples. The following equipment was used for product analysis.

Nuclear magnetic resonance analyzer: Gemini200 manufactured by Varian
Mass spectrometer: M-80B manufactured by Hitachi, Ltd. (measurement method: FD-MS analysis)
Liquid chromatography: Tosoh column (ODS-80Ts, 4.6 mm ID × 250 mm), methanol / tetrahydrofuran = 9/1 (v / v) as elution solvent, flow rate 1.0 mL / min, column temperature 40 ° C. The solution was passed through and detected with a UV-visible detector (UV-8020) manufactured by Tosoh Corporation.

  Among the tetraaminobenzene derivatives, the hydrochloride is a flow rate of 0 using a column (ODS-80Ts, 4.6 mm ID × 250 mm) manufactured by Tosoh, with acetonitrile / water = 2/1 (v / v) as an elution solvent. The solution was passed through at a column temperature of 40 ° C. at a rate of 5 mL / min, and detected with a Tosoh UV-visible detector (UV-8010).

Example 1
Synthesis of 1,4-bis (dibenzylamino) -2,5-dichlorobenzene In a 500 mL four-necked flask, 17.7 g (0.10 mol) of 2,5-dichloro-p-phenylenediamine and benzyl bromide 82. 1 g (0.48 mol), 66.3 g (0.48 mol) of potassium carbonate, and 150 g of N, N-dimethylformamide were charged. After nitrogen substitution, the reaction was carried out at 60 ° C. for 16 hours. After cooling to room temperature, the reaction solution was filtered, the obtained white solid was dissolved in 500 g of toluene, and the toluene solution was washed with 500 g of pure water. The toluene solution was concentrated to obtain 42.2 g of a white solid, and recrystallized from 150 g of o-xylene to obtain 37.5 g of a white solid of 1,4-bis (dibenzylamino) -2,5-dichlorobenzene. It was. According to the analysis of the product (liquid chromatography analysis), the purity was 97.7%.

FD-MS: 536
¹ H-NMR (CDCl ₃ ): 7.11-7.35 (20H m), 6.91 (2H s), 4.10 (8H s)
Example 2
^{N 1, N 1, N 4} , N 4 - tetrabenzyl ^-N 2, ^{N 5} - diphenyl-1,2,4,5-four-necked flask 200mL of tetraaminobenzene, 1,4-bis ( Dibenzylamino) -2,5-dichlorobenzene 11.0 g (20.5 mmol), aniline 18.5 g (0.20 mol), sodium tert-butoxide 6.0 g (62 mmol), and o-xylene 80 g were charged. Next, 90 mg (0.40 mmol) of palladium acetate and 320 mg (1.60 mmol) of tri-tert-butylphosphine were added together with 5.0 g of o-xylene, and reacted for 15 hours under reflux. After cooling to room temperature, the reaction solution was added to 100 mL of water and extracted twice with 100 mL of toluene. Purification was performed by silica gel column chromatography using tetrahydrofuran as a developing solvent. Further, recrystallization from toluene ^{50g, N 1, N 1,} N 4, N 4 - tetrabenzyl ^-N 2, ^{N 5} - 11.9g of a white solid diphenyl-1,2,4,5-aminobenzene Obtained. According to the analysis of the product (liquid chromatography analysis), the purity was 98.6%.

FD-MS: 650
¹³ C-NMR (CDCl ₃ ): 144.30, 137.65, 136.57, 131.39, 129.30, 129.03, 128.22, 127.12, 119.62, 116.08, 113 .90, 56.99
Example 3
^{N 1,} N ⁴ - diphenyl-1,2,4,5-diaminobenzene and four-necked flask 200mL of its ^{tetrahydrochloride, N 1, N 1, N} 4, N 4 - tetrabenzyl -N ² , N ⁵ -diphenyl-1,2,4,5-tetraaminobenzene 1.0 g (1.5 mmol), 10% Pd / C (PE-type manufactured by NE Chemcat) 0.10 g and tetrahydrofuran 40 g were charged. . The gas was replaced with nitrogen and further with hydrogen. The reaction was performed at 50 ° C. for 40 hours in a hydrogen atmosphere. After completion of the reaction, the reaction solution was filtered to remove solids, and the solvent was distilled off under vacuum to obtain a residue. Recrystallization from 50 mL of degassed toluene gave 0.17 g of a fine gray solid of N ¹ , N ⁴ -diphenyl-1,2,4,5-tetraaminobenzene. According to the analysis of the product (liquid chromatography analysis), the purity was 93.5%. This solid was dissolved in 100 mL of tetrahydrofuran, and 10 mL of concentrated hydrochloric acid (37%) was added. The precipitated crystals were separated by filtration and dried to obtain 0.20 g of N ¹ , N ⁴ -diphenyl-1,2,4,5-tetraaminobenzene tetrahydrochloride. According to the analysis of the product (liquid chromatography analysis), the purity was 99.7%.

FD-MS: 290
¹³ C-NMR (DMSO-d ₆ ): 146.33, 133.24, 128.51, 124.48, 116.85, 113.97, 111.44

Claims (5)

The following general formula (1)

[Wherein X represents a halogen atom. ]
The following general formula (2) obtained by benzylating 2,5-dihalogeno-p-phenylenediamine represented by the following formula (2)

[Wherein, Bn represents a benzyl group, and X represents a halogen atom. ]
1,4-bis (dibenzylamino) -2,5-dihalogenobenzenes are reacted with an aromatic amine in the presence of a palladium catalyst to give the following general formula (3):

[Wherein, Bn may be a benzyl group, Ar ¹ and Ar ² may be the same or different and each represents a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthracenyl group or a 2-anthracenyl group. ]
And a 1,4-bis (dibenzylamino) -2,5-diaminobenzene derivative represented by the following general formula (4):

[In formula, Ar < ¹ >, Ar < ² > may mutually be same or different, and represents a phenyl group, 1-naphthyl group, 2-naphthyl group, 1-anthracenyl group, or 2-anthracenyl group. ]
The manufacturing method of the tetraaminobenzene derivative shown by these. A tetraaminobenzene derivative comprising a step represented by the method for producing a tetraaminobenzene derivative according to claim 1 and a step of adding hydrochloric acid to the tetraaminobenzene derivative represented by the general formula (4) obtained in the step Manufacturing method of hydrochloride. A benzylated dihalogenophenylenediamine derivative represented by the following general formula (2).

[Wherein, Bn represents a benzyl group, and X represents a halogen atom. ] A tetraaminobenzene derivative represented by the following general formula (3).

[Wherein, Bn may be a benzyl group, Ar ¹ and Ar ² may be the same or different and each represents a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthracenyl group or a 2-anthracenyl group. ] The tetraaminobenzene derivative according to claim 4, wherein in the general formula (3), Ar ¹ and Ar ² are both phenyl groups.