KR102363365B1 - Method of manufacturing bis(trifluoromehtyl)biphenyl compound - Google Patents

Abstract

In the method for preparing a bis(trifluoromethyl)biphenyl compound according to exemplary embodiments of the present invention, a trifluoromethylaniline compound is reacted with an alkali metal halide to form a halotrifluoromethylbenzene compound. A halotrifluoromethylbenzene compound is subjected to a coupling reaction under copper catalyst conditions. The productivity of the bis(trifluoromethyl)biphenyl compound may be improved.

Description

Method for producing a bis (trifluoromethyl) biphenyl compound {METHOD OF MANUFACTURING BIS (TRIFLUOROMEHTYL) BIPHENYL COMPOUND}

It relates to a method for preparing a bis(trifluoromethyl)biphenyl compound. More specifically, it relates to a method for producing a bis(trifluoromethyl)biphenyl compound using a copper catalyst.

2,2'-bis(trifluoromethyl)biphenyl is a useful monomer for preparing a functional polymer such as polyimide or polyamidoimide that provides physical properties such as heat resistance, transparency, and high strength.

A method for preparing 2,2'-bis(trifluoromethyl)biphenyl from 2-halobenzotrifluoride, benzotrifluoride, 2,2'-substituted biphenyl and the like is known.

For example, 2,2'-bis(trifluoromethyl)biphenyl by coupling 2-bromobenzotrifluoride as a starting material under anhydrous conditions using an expensive palladium catalyst and a strong base, alkyl lithium. can be synthesized. In addition, there is a coupling manufacturing method using excess manganese as a reducing agent and cobalt bromide as a catalyst, and a Grignard intermediate is formed by reacting 2-bromobenzotrifluoride with magnesium and 2,2 through a Grignard condensation reaction. A method for preparing '-bis(trifluoromethyl)biphenyl is also known. A method of coupling nickel acetate as a catalyst using a bipyridine ligand under strong base conditions such as sodium hydride and sodium amyl oxide is known, using a bipyridine ligand and a nickel catalyst, and in the presence of potassium iodine and an excess of a reducing agent Coupling methods are known. Also, an electrochemical coupling reaction using a battery has been introduced, but the conversion rate of the reaction is low.

Most of 2-bromobenzotrifluoride is produced by diazotizing 2-trifluoromethylaniline and then performing a bromine substitution reaction with copper bromide, so the manufacturing cost is high. In addition, most of the above-described coupling reactions use expensive organic-inorganic catalysts, expensive ligand materials, and a large amount of reducing agent, so the cost is high and the yield is low despite the large amount of metal by-products being generated, so the economic feasibility is very poor.

In addition, a process of reacting 2-chlorobenzotrifluoride as a starting material and pyridine as a ligand under cobalt bromide catalyst conditions in an acetonitrile solvent is known, and a method of electrochemically coupling nickel bromide bipyridine as a catalyst is also known A process for synthesizing excess zinc powder as a reducing agent, nickel chloride as a catalyst, and triphenylphosphine as a ligand was also disclosed in Japanese Patent Laid-Open No. 1992-005248 and Japanese Patent Laid-Open No. 1992-169542, the same A method of manufacturing using nickel bromide instead of nickel chloride as a method was also disclosed in Chinese Patent Laid-Open No. 104211944. A method for synthesizing 2,2'-bis(trifluoromethyl)biphenyl by a Grignard reaction by converting 2-chlorobenzotrifluoride into a Grignard reagent is disclosed in International Patent Publication No. 2008059724 and International Patent Publication No. 2008059724 2007052516 was disclosed.

Methods using 2-chlorobenzotrifluoride as a starting material have limitations in the substitution capacity of the chlorine atom in the substituent, so they require expensive ligands, use heavy metal organic catalysts such as nickel, or use strong bases such as alkoxides. should be used While the cost of the raw material, 2-chlorobenzotrifluoride, is low, the cost of the coupling process is high, and it is difficult to recover the catalyst, so post-treatment of the used heavy metal catalysts is difficult, which is disadvantageous in terms of environment and cost.

Methods for synthesizing 2,2'-bis(trifluoromethyl)biphenyl by fluorine substitution of 2,2'-biphenyldicarboxylic acid or 2,2'-dimethylbiphenyl are disclosed in Japanese Patent Laid-Open No. 2005126331 Although known, industrial application is difficult because the cost of the fluorination reagent is high or the yield is low.

There is also a method of synthesizing 2,2'-bis(trifluoromethyl)biphenyl using butoxide and iron dichloride or manganese chloride as a catalyst at a low temperature of -78°C using benzotrifluoride, a cheap raw material, but under anhydrous conditions , low-temperature conditions, expensive catalysts and expensive bases, etc., are difficult to adopt as industrial processes due to high manufacturing costs.

On the other hand, a method of coupling from 2-iodobenzotrifluoride to a palladium-indium catalyst, a method of using a nickel bromide catalyst and an excess of zinc powder as a reducing agent, and a method of using butyllithium and iron dichloride or manganese dichloride at a low temperature of -78°C A method for coupling using as a catalyst is known.

The process using 2-iodine benzotrifluoride uses expensive iodine, so the raw material cost is high, and environmental pollution may occur due to the metal catalyst used, or a large amount of cost may be consumed in the treatment of the spent catalyst.

Accordingly, processes using 2-chlorobenzotrifluoride or 2-bromobenzotrifluoride rather than 2-iodinebenzotrifluoride as raw materials are being researched and developed.

Japanese Patent Laid-Open No. 1992-005248 Japanese Patent Laid-Open No. 1992-169542 Chinese Patent Publication No. 104211944 International Patent Publication No. 2008059724 International Patent Publication No. 2007052516 Japanese Patent Laid-Open No. 2005126331 Chinese Patent Publication No. 108864454

One object of the present invention is to provide a method for producing a bis (trifluoromethyl) biphenyl compound having excellent productivity.

1. reacting a trifluoromethylaniline compound with an alkali metal halide to form a halotrifluoromethylbenzene compound; And A method for producing a bis (trifluoromethyl) biphenyl compound comprising the step of a coupling reaction of the halotrifluoromethylbenzene compound under copper catalyst conditions.

2. The method for preparing a bis(trifluoromethyl)biphenyl compound according to the above 1, wherein the trifluoromethylaniline compound includes o-trifluoromethylaniline.

3. The method of 1 above, wherein the alkali metal halide includes sodium iodide or potassium iodide, bis(trifluoromethyl)biphenyl compound.

4. The method of 1 above, wherein the step of forming the halotrifluoromethylbenzene compound is performed through a diazonium salt intermediate, bis(trifluoromethyl)biphenyl compound.

5. The method for producing a bis (trifluoromethyl) biphenyl compound according to 4 above, wherein the diazonium salt intermediate is formed by reacting the trifluoromethylaniline compound with nitrous acid.

6. The method for preparing a bis(trifluoromethyl)biphenyl compound according to the above 1, wherein the copper catalyst is converted into a copper(I) halide during the coupling reaction.

7. The method for producing a bis(trifluoromethyl)biphenyl compound according to the above 6, further comprising the step of hydrolyzing the copper(I) halide to form copper(I) oxide.

8. The method for producing a bis(trifluoromethyl)biphenyl compound according to the above 7, wherein the hydrolysis is performed using an alkali metal hydroxide, and a regenerated alkali metal halide is formed by the hydrolysis.

9. The method for producing a bis(trifluoromethyl)biphenyl compound according to 8 above, wherein the regenerated alkali metal halide is used in the step of forming the halotrifluoromethylbenzene compound.

10. The method for producing a bis(trifluoromethyl)biphenyl compound according to the above 7, further comprising reducing the copper(I) oxide to form a regenerated copper catalyst.

11. The method for producing a bis(trifluoromethyl)biphenyl compound according to the above 10, wherein the regenerated copper catalyst is provided as the copper catalyst of the coupling reaction.

12. The method for preparing a bis(trifluoromethyl)biphenyl compound according to the above 10, wherein the reduction is performed with hydrazine or sodium borohydride.

13. The method for producing a bis(trifluoromethyl)biphenyl compound according to the above 12, wherein the hydrazine is used in 1 to 2 equivalents based on the copper (I) oxide.

14. The method for preparing a bis(trifluoromethyl)biphenyl compound according to the above 1, wherein the bis(trifluoromethyl)biphenyl compound includes 2,2'-bis(trifluoromethyl)biphenyl .

According to exemplary embodiments, high-purity bis(trifluoromethyl) in a simplified process by reacting a trifluoromethylaniline compound with an alkali metal halide to form a halotrifluoromethylbenzene compound and coupling with a copper catalyst Biphenyl compounds can be prepared.

For example, a copper halide converted from a copper catalyst is hydrolyzed to form copper (I) oxide, and a regenerated copper catalyst can be obtained simply by reducing copper (I) oxide, and the regenerated copper catalyst is used as a coupling catalyst. can be reused as

In addition, by reusing the regenerated alkali metal halide generated during hydrolysis for the formation of the halotrifluoromethylbenzene compound, it is possible to significantly improve resource utilization and yield of the process.

In addition, by increasing the reusability of the copper catalyst, it is possible to reduce the cost required for the treatment of the spent catalyst.

1 is a schematic flowchart illustrating a method for preparing a bis(trifluoromethyl)biphenyl compound according to exemplary embodiments.

Exemplary embodiments of the present invention are bis (trifluoromethyl) biphenyl compounds in which a trifluoromethylaniline compound is reacted with an alkali metal halide to form a halotrifluoromethylbenzene compound and a coupling reaction is performed under copper catalyst conditions. A manufacturing method is provided. The productivity of the bis(trifluoromethyl)biphenyl compound may be improved.

Hereinafter, with reference to the drawings, embodiments of the present invention will be described in more detail. However, the following drawings attached to the present specification illustrate preferred embodiments of the present invention, and serve to further understand the technical spirit of the present invention together with the above-described content of the present invention, so the present invention is described in such drawings It should not be construed as being limited only to the matters.

1 is a schematic flowchart illustrating a method for preparing a bis(trifluoromethyl)biphenyl compound according to exemplary embodiments.

Referring to FIG. 1 , a trifluoromethylaniline compound may be reacted with an alkali metal halide to form a halotrifluoromethylbenzene compound (eg, step S10 ).

The trifluoromethylaniline compound may include, for example, o(ortho)-trifluoromethylaniline. In this case, an o-halotrifluoromethylbenzene compound and 2,2'-bis(trifluoromethyl)biphenyl may be formed.

The alkali metal halide may be represented by MX. M may be an alkali metal, and X may be a halogen. M may include, for example, sodium (Na) or potassium (K). X may include, for example, chlorine (Cl), bromine (Br) or iodine (I). The halide of the alkali metal halide may substitute a halogen group for the amino group of the trifluoromethylaniline compound.

Preferably, X may include iodine, and the alkali metal halide may include sodium iodide or potassium iodide. In this case, the amino group of the trifluoromethylaniline compound may be substituted with an iodine group (-I) to form o-iodotrifluoromethylbenzene. The o-iodotrifluoromethylbenzene may have excellent coupling reactivity.

In exemplary embodiments, the forming of the halotrifluoromethylbenzene compound may be performed through a diazonium salt intermediate. For example, the amino group of the trifluoromethylaniline compound may be substituted with a diazonium (-N ₂ ⁺ ) group to form the diazonium salt intermediate. The diazonium group may be substituted with a halide ion (X ⁻ ) to form the halotrifluoromethylbenzene compound.

For example, the diazonium salt may be formed by the reaction of the trifluoromethylaniline compound with nitrous acid (HNO ₂ ). Nitrous acid can be formed by the reaction of sodium nitrite with hydrochloric acid.

The halotrifluoromethylbenzene compound may be subjected to a coupling reaction under copper catalyst conditions (eg, step S20 ).

A pair of carbon atoms connected to each halogen group of the two halotrifluoromethylbenzene compounds may be connected to each other to form a biphenyl structure. In this case, the bis(trifluoromethyl)biphenyl compound can be easily prepared in high yield.

The copper catalyst may include, for example, copper powder.

In some embodiments, the coupling reaction may be performed in a non-oxidizing atmosphere or a reducing atmosphere. For example, the reaction of the coupling reaction may be replaced with nitrogen gas.

In example embodiments, the copper catalyst may be converted into copper (I) halide (CuX) during the coupling reaction.

In example embodiments, the copper(I) halide may be hydrolyzed to form copper(I) oxide (Cu ₂ O) (eg, step S30 ).

The hydrolysis may be performed using alkali metal hydroxide (MOH). In this case, a regenerated alkali metal halide (MX) may be formed together with the copper (I) oxide.

In exemplary embodiments, the regenerated alkali metal halide may be used as the alkali metal halide of step S10. Thus, halogens and alkali metal halides can be reused. The use of iodine as a halogen can significantly reduce process costs.

In example embodiments, the copper (I) oxide may be reduced to form a regenerated copper catalyst (eg, step S40). The regenerated copper catalyst may be used as a catalyst for the coupling reaction (step S20). Thus, recycling of the copper catalyst within the process can be carried out. In this case, the bis(trifluoromethyl)biphenyl compound can be manufactured economically and environmentally friendly by reducing the cost and environmental pollution caused by the waste catalyst treatment.

In addition, the regenerated copper catalyst produced by the reduction may have a remarkably large surface area in the form of a fine powder. Accordingly, the reaction can be effectively promoted even with a small amount due to high catalytic activity.

In example embodiments, the reduction of the copper (I) oxide may be performed in a reactor in which the coupling reaction is performed. For example, the copper (I) oxide and the reducing agent may be introduced into the coupling reactor to simultaneously progress the reduction reaction and the coupling reaction in-situ. In this case, since the additional separation and purification process is omitted, the economical efficiency of the process may be improved. In addition, the reduced copper catalyst (regenerated copper catalyst) may be easily oxidized upon contact with oxygen and moisture to lose the coupling catalyst function, but the activity of the copper catalyst may be improved through the in-situ process.

In exemplary embodiments, the reduction may be performed by hydrazine (N ₂ H ₄ ) or sodium borohydride (NaBH ₄ ). Hydrazine and sodium borohydride can effectively convert the copper(I) oxide into a coupling catalyst as strong reducing agents. Preferably, hydrazine can be used as the reducing agent. In this case, the reduction reaction may be performed at a relatively low temperature without by-products such as boric acid or borate salt.

In exemplary embodiments, hydrazine may be used in an amount of 1 to 2 equivalents (based on the number of moles) based on the copper (I) oxide. When the amount of hydrazine used is less than 1 equivalent, the time it takes to complete the reduction reaction of the catalyst may increase, thereby reducing reaction efficiency. When the amount used is more than 2 equivalents, although the reaction rate is substantially saturated, the process cost may increase.

According to exemplary embodiments, as the recycled alkali metal halide is reused, more than 95% of halide ions may be recycled. In addition, by reusing the regenerated copper catalyst, more than 99% of copper can be recycled.

Bis(trifluoromethyl)biphenyl compounds (eg, 2,2'-bis(trifluoromethyl)biphenyl) have high heat resistance due to their rigid biphenyl structure, and reduce the planarization of the biphenyl structure. It can have high transparency by the trifluoromethyl group that interferes and attracts electrons. Accordingly, it is provided as an effective monomer of a functional polymer such as polyimide, polyamide, and polyester, and can be applied to semiconductors, displays, and the like.

In some embodiments, 2,2'-bis(trifluoromethyl)biphenyl may have a 4,4'-carbon substituted with an amino group, a hydroxyl group, or a mercapto group. Preferably, 2,2'-bis(trifluoromethyl)-4,4'-diaminobiphenyl may be provided as a monomer of polyimide or polyamide for a transparent flexible film.

Hereinafter, preferred embodiments are presented to help the understanding of the present invention, but these examples are merely illustrative of the present invention and do not limit the appended claims, and are within the scope and spirit of the present invention. It is obvious to those skilled in the art that various changes and modifications are possible, and it is natural that such variations and modifications fall within the scope of the appended claims.

Example 1

33.1 g (0.231 mol) of copper(I) oxide powder and 60 ml of dimethylformamide (DMF) were put into a reactor and heated to 90° C. while stirring. 21.87 g (0.35 mol) of 80% hydrazine hydrate was added dropwise to the reactor over 2 hours while heating and stirring. After confirming that nitrogen generation was complete, DMF was distilled under reduced pressure. DMF 60ml was added to the reactor again, and the solvent was distilled off while heating to 150° C. or higher. After cooling the reactor internal temperature to 80° C. under a nitrogen atmosphere, 114.6 g (0.421 mol) of 2-iodobenzotrifluoride with 95% purity synthesized from 2-aminobenzotrifluoride was added to the reactor. The internal temperature of the reactor was raised to 160° C., and the mixture was heated and stirred for 6 hours, and it was confirmed that the raw materials were consumed by gas chromatography analysis. After cooling to room temperature, the reaction solution was filtered to filter unreacted copper and copper iodide powder. After washing with 150 ml of methylene chloride, the filtrate was concentrated at atmospheric pressure to obtain 58.1 g (0.20 mol) of 2,2'-bis(trifluoromethyl)biphenyl.

MS data measured by mass spectrometry were as follows. As a mass spectrometer, Agilent's GC/MS 7890B/5977A was used.

Mass: 290.1, 269.1, 251.1, 237.1, 219.1, 201.2, 181.1, 152.2, 126.1, 100.7, 69.2

Example 2

After drying the copper iodide powder filtered in Example 1 in the air, it was added to 300 ml of water at room temperature, and 50.52 g (0.63 mol) of a 50% aqueous caustic soda solution was added thereto, followed by stirring at 90° C. for 6 hours. The reaction solution was cooled to room temperature and then filtered. The copper(I) oxide filtrate was washed with 50 ml of water.

The total amount of the sodium iodide aqueous solution filtrate and washing solution formed together was added to the iodination reaction of 2-aminobenzotrifluoride in Example 3 below.

Example 3

In the recovered sodium iodide aqueous solution, 3.0 g (0.02 mol) of sodium iodide was added and dissolved, and then stored at 5°C cooled. In a separate reactor, 71.4 g (0.444 mol) of 2-aminobenzotrifluoride and 100 ml of methylene chloride were added, 280 ml of water was added, and 185.1 g (1.775 mol) of a 35% aqueous hydrochloric acid solution was added dropwise while stirring for 2 hours until a homogeneous solution was obtained. stirred. The reaction solution was cooled to 0°C, and then an aqueous solution in which 34.4 g (0.488 mol) of sodium nitrite was dissolved in 68 ml of water was added dropwise while maintaining the temperature below 10°C. After stirring at the same temperature for 3 hours, the cooled aqueous sodium iodide solution was added dropwise over 2 hours while controlling the temperature of the reaction solution not to exceed 10°C. After confirming the completion of the reaction by liquid chromatography analysis, 200 ml of methylene chloride was added, stirred sufficiently, and then the layers were separated. The separated organic layer was washed with a 5% aqueous sodium sulfite solution, and then the layers were separated again and concentrated by heating at atmospheric pressure. 114.6 g of dark brown 2-iodinated benzotrifluoride was obtained with a purity of 95.6% by gas chromatography analysis.

Mass: 272.1, 252.9, 239.9, 221.9, 202.9, 191.1, 175.9, 163.9, 145.2, 125.1, 95.2, 75.2, 50.1

Example 4

The entire amount of the copper (I) oxide filtrate filtered in Example 2 was added without a drying process, and it was reduced to 21.87 g (0.35 mol) of 80% hydrazine hydrate in the same manner as in Example 1, and 2-benzoiodide obtained in Example 3 Using 114.6 g of trifluoride, 58.5 g (0.202 mol) of 2,2'-bis(trifluoromethyl)biphenyl was obtained with a purity of 95.1% by gas chromatography analysis.

Copper iodide recovered by filtration was recovered by the same method as in Example 2 with an aqueous sodium iodide solution and copper (I) oxide filtrate, and the process of Example 3 was used repeatedly in the subsequent medium.

Claims (14)

reacting the trifluoromethylaniline compound with an alkali metal halide to form a halotrifluoromethylbenzene compound;
subjecting the halotrifluoromethylbenzene compound to a coupling reaction under a copper catalyst condition and converting the copper catalyst into copper (I) halide; and
and hydrolyzing the copper(I) halide to form copper(I) oxide.
The method according to claim 1, wherein the trifluoromethylaniline compound comprises o-trifluoromethylaniline, the method for producing a bis(trifluoromethyl)biphenyl compound.
The method according to claim 1, wherein the alkali metal halide comprises sodium iodide or potassium iodide, bis (trifluoromethyl) biphenyl compound.
The method according to claim 1, wherein the step of forming the halotrifluoromethylbenzene compound is carried out through a diazonium salt intermediate, the method for producing a bis(trifluoromethyl)biphenyl compound.
The method of claim 4, wherein the diazonium salt intermediate is formed by reacting the trifluoromethylaniline compound with nitrous acid.
delete delete The method for producing a bis(trifluoromethyl)biphenyl compound according to claim 1, wherein the hydrolysis is performed using an alkali metal hydroxide, and a regenerated alkali metal halide is formed by the hydrolysis.
The method for producing a bis(trifluoromethyl)biphenyl compound according to claim 8, wherein the regenerated alkali metal halide is used in the step of forming the halotrifluoromethylbenzene compound.
The method according to claim 1, further comprising reducing the copper (I) oxide to form a regenerated copper catalyst.
The method for producing a bis(trifluoromethyl)biphenyl compound according to claim 10, wherein the regenerated copper catalyst is provided as the copper catalyst of the coupling reaction.
The method according to claim 10, wherein the reduction is performed with hydrazine or sodium borohydride.
The method for producing a bis(trifluoromethyl)biphenyl compound according to claim 12, wherein the hydrazine is used in 1 to 2 equivalents based on the copper (I) oxide.
The method according to claim 1, wherein the bis(trifluoromethyl)biphenyl compound comprises 2,2'-bis(trifluoromethyl)biphenyl.

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