JP5766053B2 - Method for producing biaryl compound - Google Patents

Description

  The present invention relates to a method for producing a biaryl compound useful in the field of electronic materials such as liquid crystal and organic EL.

  A biaryl compound is a very useful compound for use in electronic materials such as liquid crystal and organic EL (Electro Luminescence). As a method for producing these compounds, a Suzuki coupling reaction is generally used (see, for example, Non-Patent Document 1 and Non-Patent Document 2). However, in this reaction, trace by-products and unreacted raw materials may remain in the biaryl compound, and in particular, when the raw material aromatic halogen compound remains, it generally affects the performance of electronic materials. Are known. Therefore, when the biaryl compound is used for electronic materials, there is a problem that it is strongly desired to separate the remaining aromatic halogen compound.

  As a method for separating the aromatic halogen compound remaining in the biaryl compound, recrystallization, sublimation and the like are common (see, for example, Non-Patent Document 3). However, depending on the type of the aromatic halogen compound, the physical and chemical properties are similar to those of the biaryl compound, and thus purification is difficult.

  For this reason, the present inventors have repeated the above purification operation, but it is necessary to significantly reduce the yield of the biaryl compound, increase the waste due to the use of a large amount of organic solvent, and introduce an expensive sublimation apparatus. For example, there was a problem to be improved as an industrial production method. Therefore, development of a method for easily and effectively separating aromatic halogen compounds in biaryl compounds has been strongly desired.

Suzuki Akira et al., “Cross Coupling Reaction-Fundamentals and Industrial Applications”, 13-14, published by CMC Publishing, 2010 Edited by Masahiro Kotani et al., “5th edition, Experimental Chemistry Course, Synthesis of Organic Compounds VI, Organic Synthesis Using Metals”, 18, 339-340, published by Maruzen, 2004 Edited by Noriaki Hirayama, “Organic Compound Crystal Preparation Handbook-Principles and Know-how”, pages 37-55, published by Maruzen Co., Ltd., 2008

  An object of the present invention is to provide a technique for easily and effectively separating an aromatic halogen compound remaining in a biaryl compound in order to solve the problems of the conventional techniques.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have reacted an aromatic halogen compound and an aromatic boronic acid, and then added a reducing agent, thereby remaining unreacted aromatic halogen. The present inventors have found that the compound can be converted into a reduced form and separated from the biaryl compound, and the present invention has been completed.

  That is, the present invention relates to the general formula (1)

(Wherein Ar ₁ represents an optionally substituted aryl group or heteroaryl group, X represents Cl, Br or I) (hereinafter referred to as “aromatic halogen compound”). And general formula (2)

(In the formula, Ar ₂ represents an optionally substituted aryl group or heteroaryl group, and Y ₁ and Y ₂ each independently represent the same or different hydroxyl group or C 1-4 alkoxy group. Or an aromatic boronic acid (hereinafter also referred to as “aromatic boronic acid”) represented by Y ₁ and Y ₂ bonded to each other to represent an alkylenedioxyl group or catecholate group having 1 to 6 carbon atoms. A general formula (3) characterized by adding a reducing agent after the reaction.

(In the formula, Ar ₁ is the same as the general formula (1), and Ar ₂ is the same as the general formula (2).)
A biaryl compound represented by the following (hereinafter also referred to as “biaryl compound”).
In addition, the present invention provides a general formula (4) obtained by adding a reducing agent.

(In the formula, Ar ₁ is the same as the general formula (1).)
Is a method for producing the biaryl compound, wherein the reduced form (hereinafter also referred to as “reduced form”) is separated from the biaryl compound.

  ADVANTAGE OF THE INVENTION According to this invention, the method of isolate | separating the aromatic halogen compound which remains in a biaryl compound easily and effectively can be provided, and, thereby, a highly purified biaryl compound can be manufactured.

Next, the present invention will be described in more detail.
In the general formulas (1) and (2), Ar ₁ and Ar ₂ represent an optionally substituted aryl group or heteroaryl group, and these may be the same or different from each other. X represents Cl, Br, or I. Y ₁ and Y ₂ each independently represent the same or different hydroxyl group or an alkoxy group having 1 to 4 carbon atoms, or Y ₁ and Y ₂ are bonded to each other to represent an alkylenedioxyl group having 1 to 6 carbon atoms. Or represents a catecholate group. The following compounds can be given by showing a part of specific examples of the above aromatic halogen compounds or aromatic boronic acids.

  The compound of the general formula (3) [biaryl compound] is described in, for example, Journal of Organic Chemical Chemistry / Vol. 63 / No. 4 / April 2005 issue / pages 312 to 324 and cross coupling reaction-basic and industrial application / CM publication / 2010 publication / Akira Suzuki et al./pages 13 to 14) .

  The reducing agent may be added to the reaction solution after completion of the coupling reaction to carry out the reduction reaction, or the reducing agent may be reacted with the crude crystal isolated after the coupling reaction.

  The reducing agent may be (1) a combination of a palladium compound and a metal hydride compound, or (2) a. A palladium compound, b. A phosphorus compound, c. A base, d. It is preferable to use a combination of alcohols other than tertiary.

  The said palladium compound should just be a thing which does not decompose | disassemble a biaryl compound, and 0-2 divalent palladium compounds are mentioned. Specific examples include sodium hexachloropalladate tetrahydrate, potassium hexachloropalladate, palladium chloride, palladium bromide, palladium acetate, palladium acetylacetonate, dichlorobis (benzonitrile) palladium, dichlorobis (acetonitrile) palladium. Dichlorobis (triphenylphosphine) palladium, dichlorotetraamminepalladium, dichloro (cycloocta-1,5-diene) palladium, palladium trifluoroacetate, tris (dibenzylideneacetone) dipalladium, tris (dibenzylideneacetone) dipalladium chloroform complex, Examples include tetrakis (triphenylphosphine) palladium. Of these, palladium acetate, tris (dibenzylideneacetone) dipalladium, and tetrakis (triphenylphosphine) palladium are preferable. The amount of these used is usually preferably in the range of 0.01 to 20 mol% in terms of palladium with respect to 1 mol of the remaining unreacted aromatic halogen compound. The palladium compound may be a single compound or a combination of two or more compounds.

The metal hydride compound is not particularly limited as long as it does not decompose the biaryl compound, and examples thereof include sodium compounds, lithium compounds, and aluminum compounds. Specific examples include sodium hydride (NaH), sodium borohydride (NaBH ₄ ), lithium aluminum hydride (LiAlH ₄ ), aluminum hydride chloride (AlCl ₂ H), and aluminum hydride (AlH _3). ), Superhydride (registered trademark), DiBAL-H, Red Al (registered trademark), K-Selectride (registered trademark), L-Selectride (registered trademark), KS-Selectride (registered trademark), LS-Select Ride (registered trademark) and the like. Of these, sodium hydride, sodium borohydride, and lithium aluminum hydride are preferable. The amount of these used is preferably in the range of 1 to 50 mol with respect to 1 mol of the remaining aromatic halogen compound. The metal hydride compound may be a single compound or a combination of two or more compounds.

  The phosphorus compound is not particularly limited as long as it does not decompose the biaryl compound, and examples thereof include monodentate phosphorus compounds and bidentate phosphorus compounds. Specific examples include triethylphosphine, tri (tert-butyl) phosphine, tri (n-butyl) phosphine, tricyclohexylphosphine, triphenylphosphine, 1,1′-bis (diphenylphosphino) ferrocene (dppf ), 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene (XANTphos), bis [2- (diphenylphosphino) phenyl] ether (DPEphos), and the like. Of these, tri (tert-butyl) phosphine, tricyclohexylphosphine, XANTphos and DPEphos are preferred. The amount of these used is preferably in the range of 1 to 20 mol with respect to 1 mol of the palladium compound. The phosphorus compound may be a single compound or a combination of two or more compounds.

  The base is not particularly limited as long as it does not decompose the biaryl compound, and examples thereof include metal hydroxides, metal carbonates, metal phosphates, metal sulfates, and metal alkoxylates. Specific examples include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, tripotassium phosphate, sodium sulfate, sodium hydrogen sulfate, sodium. -Methoxide, sodium-ethoxide, potassium-methoxide, potassium-ethoxide, lithium-tert-butoxide, sodium-tert-butoxide, potassium-tert-butoxide and the like. Of these, potassium hydroxide, potassium carbonate, tripotassium phosphate, and sodium-tert-butoxide are preferred. The amount of these used is preferably in the range of 1 to 50 mol with respect to 1 mol of the remaining aromatic halogen compound. Moreover, a base may be used alone or in combination of two or more.

  Any alcohol other than the tertiary alcohol may be used as long as it does not decompose the biaryl compound, and examples thereof include primary alcohols and secondary alcohols. Specific examples include methanol, ethanol, propanol, isopropanol, butanol, 2-butanol and the like. Of these, butanol is preferred. The amount of these used is preferably in the range of 1 to 50 mol with respect to 1 mol of the remaining aromatic halogen compound. Moreover, alcohol may be used alone or in combination of two or more.

  The solvent used in the reduction reaction may be any solvent that does not affect the reaction, and examples thereof include ethers, aromatic hydrocarbons, aliphatic hydrocarbons, and amides. Specific examples include diethyl ether, tetrahydrofuran, o-xylene, toluene, hexane, heptane, 1,4-dioxane, 1,3-dioxane, N, N-dimethylacetamide (DMAC), 1,3- Examples thereof include dimethyl-2-imidazolidinone (DMI) and N-methylpyrrolidone (NMP). Of these, o-xylene and N, N-dimethylacetamide (DMAC) are preferred. The amount of these used is preferably in the range of 1 to 100 mol with respect to 1 mol of the crude crystals (crude biaryl compound) isolated after completion of the coupling reaction. Moreover, a solvent may be used alone or in combination.

  The temperature of the reduction reaction may be a temperature at which the biaryl compound does not decompose and is preferably in the range of 0 to 200 ° C, more preferably in the range of 50 to 150 ° C. Thus, the unreacted remaining aromatic halogen compound is reduced to a reduced form represented by the general formula (4).

  After completion of the reduction reaction, the produced inorganic salt and residual metal are removed by washing with water and filtration according to a conventional method.

  The reduced form obtained by the reduction reaction can be reduced by purification. As the purification method, recrystallization or sublimation purification is preferred.

  The reduction reaction is desirably performed in an inert gas atmosphere such as nitrogen or argon, and can be performed under normal pressure or under pressure.

  EXAMPLES The present invention will be described in more detail with reference to the following examples. However, these examples show the outline of the present invention, and the present invention is not limited to these examples.

[measuring equipment]
The reaction yield, conversion rate, and purity were calculated by HPLC (high performance liquid chromatography) analysis. The apparatus used is shown below.
HPLC apparatus: High performance liquid chromatograph LC-8020 (manufactured by Tosoh Corporation)
Column: Inertsil ODS-3V (4.6 mm ID × 250 mm) (manufactured by GL Sciences)
Detector: UV-visible detector (measurement wavelength 254 nm)

Example 1 (NPD: N, N′-bis (1-naphthylyl) -N, N′-diphenylyl) benzidine)
The inside of a 200 ml eggplant flask equipped with a thermometer and a condenser was purged with nitrogen, and then N-phenyl-N- (4-bromophenyl) -1-naphthylamine (3.74 g, 0.010 mol), N-phenyl-N- (4-boronic acid phenyl) -1-naphthylamine 3.73 g (0.011 mol), tripotassium phosphate 10.6 g (0.050 mol), pure water 20.0 g (1.11 mol), toluene 50. 0 g (0.543 mol), 0.046 g (0.05 μmol) of trisdibenzylideneacetone dipalladium, and 0.061 g (0.30 μmol) of tri-tert-butylphosphine were charged.

  The reaction vessel was heated to 85 ° C. and stirred for 24 hours. After adding 50.0 g of water, the mixture was cooled to a temperature of 25 ° C. and filtered to obtain 5.83 g of the product, crude NPD (isolated yield: 99%).

  As a result of HPLC analysis of NPD and the remaining halogen compounds as raw materials, the purity was 97.7% and 1.6%, respectively.

  Subsequently, the inside of the 500 ml eggplant flask was purged with nitrogen, and then 5.83 g of the above NPD crude crystals and 87.5 g of N, N-dimethylacetamide [15 wt. r (15 weight times as a solvent for the crude crystal, the same applies hereinafter)] and 87.5 g (15 wt.r) of o-xylene were charged.

  After heating the reaction vessel to a temperature of 140 ° C., after adding 5.0 g of N, N-dimethylacetamide solution of 168 mg (0.75 mmol) of palladium acetate and 28.4 mg (0.75 mmol) of sodium borohydride. Stir for 1 hour.

  The reaction solution was collected and analyzed by HPLC. As a result, the remaining raw material halogen compound was not detected.

  The reaction solution was cooled to a temperature of 25 ° C. and filtered to obtain 5.59 g of NPD (isolated yield: 95%). As a result of HPLC analysis of NPD and the remaining halogen compound of the raw material, the purity was 97.8% and not detected, respectively.

  Subsequently, the obtained NPD was recrystallized twice using N, N-dimethylacetamide (15 wt.r) and o-xylene (15 wt.r), and 5.05 g of NPD was isolated at a yield of 85. %. As a result of HPLC analysis of NPD and the remaining halogen compound of the raw material, the purity was 99.9% and not detected, respectively. These results are shown in Table 1.

Example 2
In place of palladium acetate and sodium borohydride, 6.9 mg (0.0075 mmol) of trisdibenzylideneacetone dipalladium, 1.5 mg (0.0075 mmol) of tri-tert-butylphosphine, and 159 mg (0.75 mmol) of tripotassium phosphate ) And n-butanol 56 mg (0.75 mmol) were used, and the same operation as in Example 1 was performed. The results are shown in Table 1.

Comparative Example 1
The same operation as in Example 1 was carried out except that palladium acetate and sodium borohydride were not used and the number of recrystallizations was increased. The results are shown in Table 1.

In Table 1, the reduction process also serves as a recrystallization process.
The following can be understood from the above examples and comparative examples.
1) Compared with Comparative Example 1, Examples 1 and 2 can be obtained with at least a high purity in the number of recrystallizations. In particular, in Comparative Example 1, although recrystallization is repeated six times, the halogen raw material cannot be detected until it is undetected, and this is in contrast to the case where detection is not detected with a small number of recrystallizations in the examples.
2) In the example, the yield is higher than that of the comparative example, and it can be efficiently manufactured.

  Since the biaryl compound obtained by this invention has high purity, it is useful for electronic material uses, such as a liquid crystal and organic EL.

Claims (2)

General formula (1)
(Wherein Ar ₁ represents an optionally substituted aryl group or heteroaryl group, X represents Cl, Br, or I), and the general formula (2)
(Wherein, Ar ₂ is substituted represents an aryl group or a heteroaryl group, Y ₁ and Y ₂ represents a hydroxyl group.) After reacting aromatic boronic acid represented by ( 1) a combination of a palladium compound and a metal hydride compound, or (2) a. A palladium compound, b. A phosphorus compound, c. A base, d. General formula (3), characterized by adding a reducing agent which is any combination of alcohols excluding tertiary
(In the formula, Ar ₁ is the same as the general formula (1), and Ar ₂ is the same as the general formula (2).)
The manufacturing method of the biaryl compound characterized by manufacturing the biaryl compound represented by these. Obtained by adding the reducing agent, the general formula (4)
(In the formula, Ar ₁ is the same as the general formula (1).)
The manufacturing method of the biaryl compound of Claim 1 which isolate | separates the reductant represented by these with a biaryl compound.