WO2014061087A1 - Use of sic as carrier in pd catalyst reaction in liquid phase, supported pd catalyst using sic as carrier, method for manufacturing same, and coupling reaction using same - Google Patents

Abstract

The present invention pertains to the use of a solid material comprising SiC as a carrier for a Pd catalyst in a transitional-metal catalytic reaction performed in the presence of a catalyst containing palladium; for example, a coupling reaction. The coupling reaction may be a Suzuki-Miyaura coupling reaction. The present invention further pertains to a method characterized in supporting a palladium catalyst on a solid material comprising SiC in a so-called Suzuki-Miyaura coupling reaction in which an organic boron compound and an organic halide are caused to react in the presence of the palladium catalyst and in the presence of a base to produce a different organic compound having carbon-carbon bonds. The present invention further pertains to a palladium catalyst supported on a solid material comprising SiC, and to a method for manufacturing the same.

Description

Use of SiC as a carrier in Pd catalytic reaction in liquid phase, supported Pd catalyst using SiC as a carrier, production method thereof, and coupling reaction using the same

The present invention relates to a palladium (Pd) catalyst supported on SiC (silicon carbide), a method for producing the same, a coupling reaction using the same, and the use of SiC as a catalyst carrier for a Pd catalytic reaction in a liquid phase. It is about. The invention particularly relates to the use of β-SiC as a catalyst support in a catalytic reaction in the liquid phase in the presence of a Pd catalyst.

The present inventor added SiC to the reaction system and tried the reaction of Suzuki-Miyaura coupling. Then, SiC did not interfere with the progress of the reaction of Suzuki-Miyaura coupling, and the reaction proceeded perfectly. At the end of the reaction, the Pd catalyst can be completely separated and recovered from the liquid phase together with SiC, and the separated and recovered SiC can be reused to perform the Suzuki-Miyaura coupling reaction again completely. The surprising discovery was that the Suzuki-Miyaura coupling reaction, which was reused, proceeded faster than when SiC was not added. The present invention is based on this discovery.

Many coupling reactions and many transition metal catalyzed reactions represented by the Suzuki-Miyaura coupling reaction carried out in the presence of a catalyst containing palladium (hereinafter referred to as Pd catalyst) are known. An application has been filed. Also, for the synthesis of complex organic compounds in the field of electrical materials such as liquid crystal materials, electroluminescent materials, and high-performance electronic materials, and in the pharmaceutical and pharmaceutical fields such as valsartan (antihypertensive agent) and boscalid (bactericidal agent). Widely used.

However, many Pd catalysts are often used in a state of being suspended and dissolved in a solvent without being attached to a carrier. Therefore, it is necessary to separate the Pd catalyst after completion of the synthesis reaction, and it is also necessary to recover expensive Pd economically. Furthermore, in the electrical material field and the pharmaceutical / pharmaceutical field, a purification process for removing Pd accompanying the product is also required.

Research on supporting a Pd catalyst on a carrier has been conducted for a long time. Catalysts containing palladium (Pd catalysts) are extremely diverse, and various studies have been conducted in various countries for gas phase reactions and liquid phase reactions.

Patent Document 1 (Japanese Patent Application Laid-Open No. 2001-514962) discloses one or more kinds of metals selected from the group consisting of copper, silver, gold, iron, cobalt, nickel, ruthenium, rhodium, osmium, iridium, palladium and platinum. A method is described for fixing a compound to a support consisting of silicon dioxide, aluminum oxide, titanium dioxide, zirconium dioxide, an oxidised mixture of these compounds, a mixed oxide of these compounds and / or aluminum silicate. In fact, a method is described in which vinyl acetate is produced in the gas phase from ethylene, acetic acid and an oxygen-containing gas in the presence of a catalyst in which a Pd / Au catalyst is fixed to a SiO ₂ support.

Patent Document 2 (WO 2008/138938) describes a method of impregnating porous silica, zirconium, graphite or (co) polymer with a palladium (II) salt. In practice, reactions such as Heck reaction, Suzuki-Miyaura reaction, Sonogashira coupling reaction, Buchwald-Hartwig reaction, etc. are performed using a catalyst in which a Pd catalyst is fixed to macroporous resin beads.

Patent Document 3 (WO2009 / 110531) describes an example in which a Suzuki-Miyaura cross-coupling reaction or the like is performed using a specific organosilicon compound as a carrier.

Non-Patent Document 1 (Journal of Synthetic Organic Chemistry, Vol. 70p, No. 7, 2012, 711-721) describes a summary of research on supported Pd catalysts for liquid phase reactions. It is described that various materials such as silica, zeolite, clay minerals, metal oxides, organic polymers and the like have been developed as carriers for heterogeneous Pd catalysts used in reactions and the like. This paper shows the results of various reactions using a polystyrene-polydivinylbenzene copolymer carrier. Furthermore, experiments have been conducted from the viewpoint of recovery and reuse of the Pd catalyst. According to this document, it is described that the Suzuki-Miyaura-Miyaura cross-coupling reaction was quantitatively performed repeatedly using the same polymer support at least four times.

Pd catalyst is also used in many gas phase reactions, and many patents related to it have been filed. Furthermore, research using a Pd catalyst using SiC as a carrier, which is the subject of the present invention, has also been conducted.

Non-patent document 1 (Journal of Catalysis 173, 374-382, 1998) carried out at a pressure of 200 to 600 ° C at atmospheric pressure using SiC as a support of a Pd catalyst used in a reaction requiring heat resistance. The research results of total oxidation of methane are described.

Non-Patent Document 3 (Applied Catalysis A General 266 (2004) 21-27) describes a method of catalytic combustion using a Pd catalyst in which particulate carbon in the exhaust gas of a diesel fuel is supported on a β-SiC support. Yes. When β-SiC support is used, it has been confirmed that the catalyst performance (conversion rate) is close to 100% by repeating four times at a temperature close to 400 ° C.

Although there are other researches for supporting SiC with Pd catalyst as shown in Non-Patent Documents 1 and 2, all of them are reactions requiring high temperature, for example, oxidation of combustion gas and exhaust gas (combustion). In this study, the fire resistance of the carrier was studied, and the function as a carrier in a precise organic reaction in the liquid phase was not expected.

On the other hand, research using SiC as a carrier has also been carried out. However, as far as the present applicant knows, there has been no report that actually tried the function of SiC as a carrier in a precise organic synthesis reaction in a liquid phase.

Pd catalysts are expensive, and if they can be recovered and reused, the cost of useful organic synthesis reactions such as the Suzuki-Miyaura coupling reaction can be greatly reduced. Further, after the synthesis reaction, the Pd catalyst can be easily separated from the liquid phase reaction system by a simple operation such as filtration, and if the Pd catalyst remaining in the desired product is substantially eliminated, the synthesis cost can be further reduced. Can do.

Therefore, there is a need for a carrier capable of meeting such demands and a supported Pd catalyst supported on the carrier.

[Patent Document 1] Japanese Patent Application Laid-Open Publication No. 2001-514962 [Patent Document 2] International Patent Publication No. WO2008 / 138938 [Patent Document 3] International Patent Publication No. WO2009 / 110531

[Non-patent Document 1] Journal of Synthetic Organic Chemistry, Vol. 70p, No. 7, 2012, 711-721
[Non-Patent Document 2] Journal of Catalysis 173, 374-382 (1998)
[Non-Patent Document 3] Applied Catalysis A General 266 (2004) 21-27

An object of the present invention is to provide a carrier capable of meeting the above needs. That is, the object of the present invention is to recover and reuse an expensive Pd catalyst used in a liquid phase organic synthesis reaction such as the Suzuki-Miyaura coupling reaction, and after the synthesis reaction, the Pd catalyst is converted into a liquid phase reaction system. It is an object of the present invention to provide a support that can be easily separated by simple operation such as filtration from the Pd catalyst and substantially eliminates the Pd catalyst remaining in the desired product.

Another object of the present invention is to react an organic boron compound and an organic halide in the presence of a palladium catalyst in the presence of a base so that the carbon in the organic boron compound is bonded to the carbon in the organic halide. In the so-called Suzuki-Miyaura coupling reaction for producing an organic compound of the present invention, a method for carrying out the reaction by supporting the palladium catalyst on a solid material is provided.

Still another object of the present invention is to provide a novel palladium catalyst for use in the Suzuki-Miyaura coupling reaction.

Still another object of the present invention is to provide a method for producing the supported palladium catalyst.

The object of the present invention is the use of a solid material comprising SiC as a support for a Pd catalyst in a transition metal catalyzed reaction carried out in the liquid phase in the presence of a palladium-containing catalyst (Pd catalyst), for example a coupling reaction. is there.

Another object of the present invention is to react an organic boron compound and an organic halide in the presence of a palladium catalyst in the presence of a base to combine carbon in the organic boron compound and carbon in the organic halide. In the so-called Suzuki-Miyaura coupling reaction for producing the organic compound, the palladium catalyst is supported on a solid material made of SiC.

Still another object of the present invention is to produce another organic compound in which the carbon in the organic boron compound and the carbon in the organic halide are combined by reacting the organic boron compound with the organic halide in the presence of a base. There is a palladium catalyst supported on a solid material made of SiC, which is used in the so-called Suzuki-Miyaura coupling reaction.

Still another object of the present invention is to provide a supported palladium characterized in that a palladium catalyst used in the Suzuki-Miyaura coupling reaction is brought into contact with a solid material made of SiC to fix the palladium catalyst on the solid material made of SiC. It is in the manufacturing method of a catalyst.

By using the present invention, an expensive Pd catalyst can be recovered and reused, and the cost of an organic synthesis reaction in a liquid phase can be greatly reduced. The supported Pd catalyst according to the present invention is separated after completion of the synthesis reaction, and the same reaction can be repeated at least 5 times or more using new raw materials.
Furthermore, in the present invention, the Pd catalyst can be easily separated from the liquid phase reaction system after completion of the synthesis reaction. Further, the Pd catalyst remaining in the desired product can be substantially zero.
Since the SiC support used in the present invention is resistant to heat, acid and mechanical stress, it has an advantage that the supported catalyst is hardly deteriorated even if it is used repeatedly.

The use of heterogeneous palladium catalyst or β-SiC in the presence of homogeneous palladium catalyst characterized in that palladium is immobilized on β-SiC according to the present invention exhibits excellent effects as a catalyst for organic synthesis reaction. To do. In particular, an arylboric acid represented by the following general formula (I) or a derivative thereof or an arylboric anhydride represented by the following general formula (II) and an aromatic compound represented by the following general formula (III) are used as a base. When this catalyst is used for the production of a biaryl derivative represented by the following general formula (IV), which is characterized by reacting in a solvent in the presence of, a high yield can be obtained. Further, after the reaction, the catalyst can be easily separated by suction filtration or the like to obtain a heterogeneous palladium catalyst that can be reused.

FIG. 3 is a graph showing the possibility of repeated use of the supported Pd catalyst used in Example 3.

The solid material used as a carrier in the present invention is made of silicon carbide “SiC”. This SiC includes α-SiC and β-SiC depending on the crystal structure. In the present invention, either α-SiC or β-SiC can be used as the carrier, but β-SiC is preferably used.
The amount of β-SiC used is preferably 2 to 100 times the weight of the number of moles of the palladium catalyst, more preferably 3 to 20 times the weight. The amount (ratio) of the palladium catalyst supported on β-SiC can be easily determined by a person skilled in the art through experiments.

Α-SiC has been used for a long time as an abrasive, and is commercially available as an abrasive or a ceramic material. When using a commercially available abrasive or ceramic material, it is necessary to investigate in advance the amount of impurities involved in the reaction, particularly the amount of metal mixed in. Moreover, when using for the synthesis | combination of the compound used by a pharmaceutical and an electronic material, it is necessary to refine | purify so that an impurity may not remain in a final product.

β-SiC is commercially available as a heat resistant material. β-SiC can be produced by various methods. Generally, it can be produced by reacting reactive carbon and SiO ₂ vapor at a temperature of 1100 ° C. or higher, or by molding, carbonizing, and carburizing paste-like polymer and silicon powder. . The β-SiC used in the present invention is available from the French company: SICAT, with the following specifications, and generally has a surface area of 10 to 120 m ² / g.

Standard grade product of β-SiC pellet (model number SD0050), diameter 1 mm, length 2 mm, BET specific surface area 25 m ² / g, pore volume 0.5 cc / g, pore diameter 10-500 nm
β-SiC microsphere standard grade (model number SD0025), diameter 100 μm, BET specific surface area 25 m ² / g, pore volume 0.5 cc / g, pore diameter 10-500 nm

This SICAT β-SiC was produced by the production method described in Japanese Patent No. 4166283, “catalyst support based on silicon carbide having a large specific surface area in the form of granules having improved mechanical properties”. .

Several studies have already been conducted on the behavior of Pd metal on the SiC surface, including the following documents.
[Non-Patent Document 4] Journal of Applied Physics 106, 123504 (2009)

The principle and mechanism for explaining the phenomenon occurring between the organic Pd catalyst used in the present invention and the β-SiC solid is currently unknown. However, when β-SiC is suspended in the reaction medium and the reaction medium is analyzed with an ICP emission spectrometer after stirring, the emission peak due to the presence of palladium disappears, so that the Pd catalyst adheres to and adsorbs on SiC. Although it is thought to have been sorbed, it is not bound by any particular theory.

The heterogeneous palladium catalyst of the present invention is characterized in that palladium is immobilized on β-SiC. SiC is an α shown by a combination of β-SiC having a zinc blende type structure (denoted as 3C), and a zinc blende type and a wurtzite type structure that is the same as this. -There is SiC. α-SiC is mainly produced as an abrasive, industrially, by the Acheson method. SiC produced by the Atchison method usually has a coarse particle size, and even fine ones have an average of about 5 μm (JIS3000), and an ultrafine pulverization step is further required as a raw material for sintering.

Β-SiC is mainly manufactured for sintering, and synthetic methods based on solid phase reactions, gas phase reactions, etc. have been developed. Β-SiC is also synthesized in the low temperature region of the reaction by the Atchison method. The gas phase reaction method is a method of synthesis by reaction of silane gas or methane gas or thermal decomposition of polycarbosilane or the like, and ultrafine powder of 0.1 μm or less can be obtained with high purity. When sintered at a temperature exceeding about 2100 ° C., abnormal grain growth occurs due to the phase transition to α-SiC.

Β-SiC used in the examples of the present invention is β-silicon carbide manufactured by SICAT and has a surface area of 10 to 120 m ² / g. The SiC-based catalyst carrier has characteristics such as a high surface area, control pores, corrosion resistance, hydrothermal resistance, and excellent mechanical strength.

Β-SiC is usually used in the form of pellets, granules, and powders, but the shape is not particularly limited. However, it is advantageous to use pellets and granules from the viewpoint of filtration performance and efficiency during separation, and the dimensions are 0.1 nm to 10 mm, preferably 1 μm to 1 mm, more preferably 5 μm to 0.5 mm.

A method of supporting (impregnating and containing) a Pd catalyst on SiC, which is a solid material, is arbitrary, and a method of impregnating a Pd catalyst with a known carrier such as silica or alumina can be used. Generally, it can be adjusted by dispersing SiC in a suitable solvent, adding the desired Pd catalyst to the dispersion, stirring and mixing, drying, and calcination. In some cases, it is necessary to use a co-catalyst to bring about the catalytic activity, or to use specific pH conditions, salt concentration conditions, and the like.

When carrying out reactions such as the Suzuki-Miyaura coupling reaction in the method of the present invention, the supported Pd catalyst of the present invention can be used in any of the following methods of use:
(1) A method in which a supported Pd catalyst in which a Pd catalyst is impregnated (contained) in advance on a SiC carrier is prepared in advance and added to a reactor containing reaction raw materials (preliminary adjustment method)
(2) A method of making a supported Pd catalyst in situ (in-situ, in the reaction system) by adding a Pd catalyst and a SiC carrier in a reactor containing reaction raw materials (in-situ method)

Since the supported Pd catalyst supported on the SiC support of the present invention can be prepared by any of the above methods (1) and (2), the Pd catalyst is supported on the SiC support by the method (2) during the 0th reaction, By separating from the product at the end of the reaction, a supported Pd catalyst is formed on the solid phase. Since the solid phase thus obtained can be used in the next first reaction, it can be said that the 0th reaction itself is the preliminary adjustment stage of the supported Pd catalyst of the above (1).

The “coupling reaction” targeted by the present invention may be a homo-coupling reaction or a cross-coupling reaction. However, the advantage of being repeatable is particularly advantageous for use in reactions catalyzed by expensive transition metals such as palladium. The present invention is particularly advantageous for use in the Suzuki-Miyaura coupling reaction.

The present invention is further applicable to general “transition metal catalyzed reactions”. Regarding the transition metal catalyzed reaction using palladium including the Suzuki-Miyaura coupling reaction, the following documents can be referred to.
[Non-Patent Document 5] by Jiro Jiro, "Transition metal catalysis for organic synthesis", Tokyo Kagaku Dojin, February 25, 2008, Chapter 2, "Organic synthesis using palladium"

Typical examples of the cross-coupling reaction include the following reactions.
(1) Suzuki-Miyaura coupling reaction Cross-coupling of organic boron compounds and organic halides under basic conditions using transition metals such as palladium as catalysts (2) Mizorogi-Heck coupling reaction Reaction to synthesize alkenyl aryl compounds by cross-coupling terminal alkene and aryl halide etc. under basic conditions using transition metal as catalyst (3) Negishi coupling reaction Using transition metal such as palladium and nickel as catalyst (4) Stille coupling reaction Cross coupling of organic tin compounds and organic halides using transition metals such as palladium as catalysts (5)辻 -Trous coupling reaction Catalyzing transition metals such as palladium Reaction to synthesize allylic alkylation products by cross-coupling allyl esters and organic nucleophiles under basic conditions (6) Sonogashira coupling reaction Basic conditions using transition metal such as palladium as catalyst (7) Kumada-Tamao coupling reaction Grignard reagents and organic halides using transition metals such as nickel and palladium as catalysts (8) Buchwald-Hartwick coupling reaction Using a transition metal such as palladium as a catalyst, the aryl halide or aryl ether is cross-coupled with an aryl halide and an amine or alcohol under basic conditions. Reaction to synthesize

The SiC carrier of the present invention is particularly advantageously applied to a Pd catalyst, particularly an organic Pd catalyst, but can also be applied to a catalyst of a metal other than Pd. The supported Pd catalyst of the present invention is effective for all the above-described cross-coupling reactions. Examples of its use in the Suzuki-Miyaura coupling reaction, which is particularly important industrially, will be described below.

The Suzuki-Miyaura coupling reaction is a reaction in which an organic boron compound and an organic halide are generally reacted in the presence of a palladium catalyst in the presence of a base to produce another organic compound having a carbon-carbon bond. It is known per se and there are many documents, which are described in numerous patent applications.

The most well known palladium catalyst used in the Suzuki-Miyaura coupling reaction is tetrakis (triphenylphosphine) palladium (0), but bis (dibenzylideneacetone) palladium (0), tris (dibenzylideneacetone). ) Palladium (0), dichlorobis (triphenylphosphine) palladium (II), palladium (II) acetate, palladium (II) chloride, bis (acetylacetonato) palladium (II), palladium (II) acetate / triscyclohexylphosphine Or palladium (II) acetate having a ligand such as bis (diphenylphosphaneferrocenyl) palladium (II) chloride or dicyclohexyl (2 ′, 4 ′, 6′-triisopropylbiphenyl-2-yl) phosphine Like the catalyst There.

The base coexisting in the reaction system can be an organic base or an inorganic base, but an inorganic base is preferable. Examples thereof include sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, phosphorus Examples include potassium acid and sodium acetate.

A solvent is generally used for the reaction, ethers such as tetrahydrofuran, diethyl ether and dimethoxyethane, saturated hydrocarbons such as pentane, hexane, heptane and octane, benzenes such as benzene, toluene, xylene and chlorobenzene, dimethylformamide or Carboxamides such as dimethylacetamide, alkyl sulfoxides such as dimethyl sulfoxide, alcohols such as N-methylpyrrolidone, methanol or ethanol, and / or a mixed system (two-phase system) of water and an organic solvent are used.

The reaction generally proceeds at room temperature to about 150 ° C., and the reaction time may be about 1 hour to 10 hours, but the reaction time can be adjusted as necessary.

The organic boron compound and the organic halide are appropriately selected according to the desired product. Hereinafter, although a method for synthesizing a biaryl compound will be described as a representative example of the Suzuki-Miyaura coupling reaction, it is not limited to this reaction.

Raw materials used for the synthesis of biaryl compounds by the Suzuki-Miyaura coupling reaction are aryl halides and arylboronic acids. These aryl groups may be substituted with a substituent.
The base coexisting in the reaction system can be an organic base or an inorganic base, but an inorganic base is preferable. Examples thereof include sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, phosphorus Examples include potassium acid and sodium acetate.
Although a solvent is not necessarily required for the reaction, a solvent is generally used. Ethers such as tetrahydrofuran, diethyl ether and dimethoxyethane, saturated hydrocarbons such as pentane, hexane, heptane and octane, benzene, toluene, xylene and chlorobenzene Benzenes, carboxamides such as dimethylformamide or dimethylacetamide, alkyl sulfoxides such as dimethyl sulfoxide, alcohols such as N-methylpyrrolidone, methanol or ethanol and / or a mixture of water and an organic solvent (two-phase system) Etc. are used.

The separation of the supported catalyst after the reaction can be easily performed by a physical separation method such as filtration. The separated wet cake (solid content) can be reused as a catalyst for the next cross-coupling reaction. On the other hand, the product after the reaction can be easily carried out by removing the supported catalyst by filtration or the like, followed by a conventional purification method well known to those skilled in the art, such as distillation and recrystallization. If it is necessary to remove trace metals, more precise separation can be performed.

The present invention relates to an arylboric acid represented by the following general formula (I) or a derivative thereof or an arylboric anhydride represented by the following general formula (II), an aromatic compound represented by the following general formula (III), Is reacted in a solvent in the presence of a base and a heterogeneous palladium catalyst for cross coupling in which palladium is immobilized on β-SiC, or in the presence of a homogeneous palladium catalyst and β-SiC. A method for producing a biaryl derivative represented by IV) is provided.

Aryl boric acid (I):

(In the formula, R is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or an alkyl group having 2 to 6 carbon atoms. It may have an alkynyl group, an alkoxy group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, a cyano group, a formyl group, an acyl group having 2 to 7 carbon atoms, or an alkyl group having 1 to 6 carbon atoms. Benzoyl group, alkoxycarbonyl group having 2 to 7 carbon atoms, phenoxycarbonyl group which may have an alkyl group having 1 to 6 carbon atoms, amino group which may have an alkyl group having 1 to 6 carbon atoms, carbon number A sulfonyl group having an amide group optionally having 1 to 6 alkyl groups, a nitro group, an alkyl group having 1 to 6 carbon atoms or a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, carbon number An alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms A sulfonic acid ester group having a phenyl group which may have a group, fluorine, or a fluoroalkyl group having 1 to 6 carbon atoms; Y is a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, A phenoxy group, a cyclohexyloxy group which may have 6 alkyl groups, or a group represented by the following general formula a, b or c with two Ys:

(In each formula, q is 1, 2, 3 or 4, and r and s are 2, 3, 4 or 5, respectively)

（式中、Ｒは前記と同じ意味を有する） Aryl boric anhydride (II):

(Wherein R has the same meaning as above)

Aromatic compound (III):
ADX (III)
(In the formula, A is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, or an alkyl group having 2 to 6 carbon atoms. It may have an alkynyl group, an alkoxy group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, a cyano group, a formyl group, an acyl group having 2 to 7 carbon atoms, or an alkyl group having 1 to 6 carbon atoms. Benzoyl group, alkoxycarbonyl group having 2 to 7 carbon atoms, phenoxycarbonyl group which may have an alkyl group having 1 to 6 carbon atoms, amino group which may have an alkyl group having 1 to 6 carbon atoms, carbon number A sulfonyl group having an amide group optionally having 1 to 6 alkyl groups, a nitro group, an alkyl group having 1 to 6 carbon atoms or a phenyl group optionally having an alkyl group having 1 to 6 carbon atoms, carbon number An alkyl group having 1 to 6 carbon atoms or an alkyl group having 1 to 6 carbon atoms Indicates a sulfonic acid ester group, a fluorine or a fluoroalkyl group having 1 to 6 carbon atoms having a phenyl group which may have a group,
D represents phenylene, naphthylene, pyridinediyl, quinolinediyl, pyrimidinediyl, triazinediyl, frangyl, benzofuranyl, thiophenediyl or benzothiophenediyl;
X represents chlorine, bromine, iodine, mesylate group and arenesulfonate group)

（式中、Ｒ、Ａ、Ｄは上記と同じ意味を有する） Biaryl derivative (IV):

(Wherein R, A and D have the same meaning as above)

Immobilization of palladium on β-SiC can be obtained, for example, by adding β-SiC to a solution of palladium acetate dissolved in methanol and mixing. The amount of palladium immobilized on β-SiC is preferably 0.1 to 5.0 mmol, more preferably 0.5 to 3.0 mmol per g of β-SiC.

When the reaction is carried out in the presence of a homogeneous palladium catalyst and β-SiC, the best known palladium catalyst is tetrakis (triphenylphosphine) palladium (0), but bis (dibenzylideneacetone) palladium. (0), tris (dibenzylideneacetone) dipalladium (0), dichlorobis (triphenylphosphine) palladium (II), palladium (II) acetate, palladium (II) chloride, bis (acetylacetonato) palladium (II), Palladium (II) acetate / triscyclohexylphosphine or bis (diphenylphosphaneferrocenyl) palladium (II) chloride or dicyclohexyl (2 ′, 4 ′, 6′-triisopropylbiphenyl-2-yl) phosphine Palladium acetate with ligand A catalyst such as (II) is preferred. The β-SiC used is preferably 2 to 100 times the weight of the number of moles of palladium catalyst, more preferably 3 to 20 times the weight.

The arylboric acid represented by the above general formula (I) or a derivative thereof or the arylboric acid anhydride represented by the above general formula (II) includes phenylboric acid; p-methylphenylboric acid, m-isopropylphenylboric acid, etc. Alkyl-substituted phenylboric acids; alkenyl-substituted phenylboric acids such as p-isopropenylphenylboric acid; alkynyl-substituted phenylboric acids such as p-ethynylphenylboric acid; aryl-substituted boric acids such as p-biphenylboric acid; m-methoxyphenylboric acid , Alkoxy-substituted phenylboric acids such as p-butoxyphenylboric acid, alkylthio-substituted phenylboric acids such as p-methylthiophenylboric acid; cyano-substituted phenylboric acids; formyl-substituted phenylboric acids; acyl-substituted phenylphosphoric acids such as p-acetylphenylboric acid Acids; aroyl-substituted phenylboric acids such as p-benzoylphenylboric acid; alkoxycarbonyl-substituted phenylboric acids such as p-methoxycarbonylphenylboric acid; phenoxycarbonyl-substituted phenylboric acids such as p-methylphenoxycarbonylphenylboric acid; p-aminophenyl Amino-substituted phenylboric acids such as boric acid and p-dimethylaminophenylboric acid; Amido-substituted phenylboric acids such as p-carbamoylphenylboric acid and p-monomethylcarbamoylphenylboric acid; p-methylsulfonylphenylboric acid and p-tolylsulfonyl Sulfonyl-substituted phenylboric acids such as phenylboric acid; fluorophenylboric acids; fluoroalkyl-substituted phenylboric acids such as trifluoromethylphenylboric acid, and their alkyl esters Esters such as phenyl ester, acid anhydride, and others. These aryl boric acids or their derivatives or aryl boric anhydrides may be used in combination of two or more.

Examples of the aromatic compound which is the other raw material represented by the general formula (III) are as follows: D in the general formula (III) is phenylene, naphthylene, pyridinediyl, pyrimidinediyl, triazinediyl, quinolinediyl, frangylyl, benzofuran Those showing a diyl, thiophenediyl or benzothiophenediyl group. X is preferably a halogen such as chlorine, bromine or iodine, and A is hydrogen, an alkyl group, an acyl group, an aroyl group, an alkoxy group, a cyano group, an aldehyde group, a carboxylic acid ester group, an amide group or an amino group. be able to.

Specifically, when D is, for example, a phenylene group, examples of the aromatic compound represented by the general formula (III) include halogenated benzenes such as bromobenzene, chlorobenzene and p-bromotoluene; p-chlorobenzaldehyde Halogenated benzenes such as p-bromoanisole, m-chloroanisole, p-chloro (2-methoxymethyl) benzene; halogenated benzoes such as o-chlorobenzonitrile and p-chlorobenzonitrile Nitriles; Halogenated benzoates such as methyl o-chlorobenzoate and methyl p-bromobenzoate; Halogenated anilines such as p-chloroaniline and p-chloro-N, N-dimethylaniline; p-iodobenzoate Halogenation of acid amide, p-chloro-N, N-dimethylbenzoic acid amide, etc. Benzoic acid amides; halogenated acylbenzenes such as p-bromoacetophenone, p-chloroacetophenone, p-bromobenzophenone, or halogenated benzenes having multiple substituents such as 2,4-dimethoxy-5-aminochlorobenzene Examples can be given.

The ratio of the arylboric acid represented by the general formula (I) or a derivative thereof and the aromatic compound represented by the general formula (III) is usually 1 mol of the aromatic compound represented by the general formula (III). Arylboric acid or its derivative is 0.8 to 1.5 mol, preferably 1 to 1.3 mol. The ratio of the arylboric anhydride represented by the general formula (II) and the aromatic compound represented by the general formula (III) is usually 1 mol of the aromatic compound represented by the general formula (III). The amount of aryl boric anhydride is 0.3 to 0.5 mol, preferably 0.33 to 0.43 mol.

Solvents used in the production method of the present invention include ethers such as tetrahydrofuran, diethyl ether and dimethoxyethane, saturated hydrocarbons such as pentane, hexane, heptane and octane, benzenes such as benzene, toluene, xylene and chlorobenzene, dimethyl Carboxamides such as formamide or dimethylacetamide, alkyl sulfoxides such as dimethyl sulfoxide, alcohols such as N-methylpyrrolidone, methanol or ethanol, and / or a mixed system (two-phase system) of water and an organic solvent are used. The amount used is not particularly limited, but is usually about 700 to 3000 parts by weight with respect to 100 parts by weight of the aromatic compound represented by the general formula (IV) from the viewpoint of operability and the like from an industrial viewpoint. preferable.

The base used in the production method of the present invention can be an organic base or an inorganic base, but an inorganic base is preferable. Examples thereof include sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, and phosphoric acid. Examples thereof include sodium, potassium phosphate, sodium acetate and the like. The amount used is 1 to 5 mol, preferably 1 to 3 mol, per 1 mol of the aromatic compound represented by formula (III).

The production method of the present invention is characterized by the arylboric acid represented by the general formula (I) or a derivative thereof or the arylboric anhydride represented by the general formula (II) and the aromatic compound represented by the general formula (III) In this reaction, a heterogeneous palladium catalyst characterized in that palladium is immobilized on β-SiC or β-SiC is used in the presence of a homogeneous palladium catalyst. The amount of the palladium catalyst used is generally preferably in the range of 0.01 to 5.00 mol%, more preferably in the range of 0.05 to 3.00 mol% with respect to the aromatic compound represented by the general formula (III). is there.

The ratio of the arylboric acid represented by the general formula (I) or a derivative thereof and the aromatic compound represented by the general formula (III) is usually 1 mol of the aromatic compound represented by the general formula (III). Arylboric acid or its derivative is 0.8 to 1.5 mol, preferably 1 to 1.3 mol.

Similarly, the ratio of the arylboric anhydride represented by the general formula (II) to the aromatic compound represented by the general formula (III) is usually 1 mol of the aromatic compound represented by the general formula (III). The amount of aryl boric anhydride is 0.3 to 0.5 mol, preferably 0.33 to 0.43 mol.

The reaction temperature of the reaction of the production method of the present invention is room temperature to 120 ° C., preferably room temperature to 100 ° C. The reaction time varies depending on the reaction temperature, the amount of catalyst and the like, but is usually 1 to 24 hours, preferably 2 to 8 hours. The reaction pressure is not particularly limited, but can usually be performed under atmospheric pressure.

In order to prevent the catalyst from being deactivated by oxygen during the reaction, the reaction is preferably performed in an inert gas atmosphere, for example, in a nitrogen gas or argon gas atmosphere.

The catalyst can be easily separated by suction filtration after the reaction. The separated cake can be used as it is as a heterogeneous palladium catalyst and reused in the next new reaction.

In order to improve the purity of the obtained biaryl derivative represented by the general formula (IV) which is the target compound of the present invention, a purification operation may be performed. For example, hydrochloric acid is added to the reaction solution and separated into two layers, followed by liquid separation, washing with an aqueous solution of sodium hydroxide, aqueous solution of sodium hypochlorite, saturated saline, etc., followed by concentration, crystallization, crystallization, etc. A high-purity product can be obtained by performing the purification operation described above. Further, it can be treated with silica gel, alumina or the like.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

Example 1
Preparation of heterogeneous palladium catalyst (“Pd / β-SiC catalyst 1”) In an argon atmosphere, 0.1121 g of palladium acetate (manufacturer, Wako Pure Chemicals) in 6 ml of methanol (purity 99.8%) in a 25 ml flask ) And 1.0022 g of granules (Micro Spheres manufactured by SICAT, model number SD0025, diameter 100 μm, BET specific surface area 25 m ² / g, pore volume 0.5 cc / g, pore diameter 10 to 500 nm) is suspended, and gently stirred at room temperature for 5 days. The change in the absorption area of the solution is measured using a UV detector (JASCO, wavelength: 400 nm), and the concentration of palladium acetate in the solution decreases. After confirming that the area gradually decreased with time, when the decrease in the area was almost flat, the stirring was stopped and the solid matter was separated by suction filtration. Was .40 3 hours at ° C., dried under reduced pressure to give a black powder 0.9031G. Black powder thus obtained referred to as "Pd / beta-SiC catalyst 1". It was confirmed by a gravimetric method that the ratio of Pd in the black powder was 5% by weight. This 5% by weight was calculated by the following gravimetric method.
(Pd amount in the charged Pd acetate-mother liquor concentration residue amount) / prepared Pd / β-SiC amount × 100
(0.0530g-0.0105g) /0.9031g×100=4.7%

Example 2
Synthesis of biphenyl by Suzuki-Miyaura coupling reaction using “Pd / β-SiC catalyst 1” In a 25-ml reaction vessel equipped with a stirrer, 0.5146 g (2.7 mmol) of 4-bromobenzaldehyde, 3770 g (3.0 mmol) of phenylboric acid, 3.69 g (9.5 mmol) of sodium phosphate dodecahydrate, 10 ml of 50% aqueous isopropyl alcohol (IPA) solution, 0. 0484 g of 5% “Pd / β-SiC catalyst 1” (0.021 mmol as Pd) was charged. The resulting mixture was stirred for 4 hours at room temperature under stirring in an argon atmosphere. The stirring speed was 700 rpm. Biphenyl was observed at 99% reaction conversion. The biphenyl yield before purity conversion was almost 100%. The biphenyl yield was calculated from the theoretical amount of the product 4-phenylbenzaldehyde (biphenyl) from 4-bromobenzaldehyde and calculated by the following method (biphenyl yield is not converted to purity).
Biphenyl yield g / biphenyl theoretical amount g × 100
0.5271 g / 0.5068 g × 100 = 104.0%

After completion of the reaction, the reaction solution was suction filtered to collect the solid content. In order to prove that this solid content shows the same catalytic performance as the Pd / β-SiC catalyst 1, a second synthesis experiment was conducted using the solid content. The charged amount of the reaction product was the same as the first time except that the above solid content was used in place of the “Pd / β-SiC catalyst 1” obtained in Example 1. The second time, biphenyl was observed at a reaction conversion rate of 81%. The product was evaluated by gas chromatography (GC).

Example 3
Synthesis of in situ biphenyl using Suzuki-Miyaura coupling reaction A reaction vessel equipped with a reflux condenser equipped with a stirrer was charged with 15.7 g (100 mmol) of bromobenzene, 12.2 g (100 mmol) of phenylboric acid, 0.8 g (100 mmol) of potassium carbonate, 100 ml of dimethoxyethane (DME), 100 ml of degassed water, 2.3 g (2 mmol) of tetrakistriphenylphosphine palladium (manufactured by NE Chemcat), 0 .70 g of β-SiC (Micro Spheres manufactured by SICAT, model number SD0025, diameter 100 μm, BET specific surface area 25 m ² / g, pore volume 0.5 cc / g, pore diameter 10 to 500 nm), The resulting mixture was stirred at room temperature for 24 hours under an argon atmosphere. The stirring speed was 150 rpm. Biphenyl was obtained with a reaction conversion of 93%. This first synthesis experiment is called the 0th synthesis experiment. The reaction conversion rate to biphenyl was determined by “high performance liquid chromatography (HPLC)” analysis.

After completion of the reaction, the reaction solution was suction filtered to collect the solid content. A first synthesis experiment was performed using the solid content as it was filtered under suction. The amount of reaction raw materials charged was the same as in the 0th time except that 2.3 g (2 mmol) of tetrakistriphenylphosphine palladium and 0.70 g of β-SiC used in Example 1 were not used. The first reaction conversion rate of biphenyl was 95%.

Similarly, the second synthesis experiment was performed using the solid content of the reaction solution obtained in the first synthesis experiment as it was suction filtered. The reaction conversion rate to biphenyl in the second synthesis experiment was improved to 99%.
Similarly, a third synthesis experiment was performed using the solid content of the reaction solution obtained in the second synthesis experiment while suction filtration was performed. The reaction conversion rate to biphenyl in the third synthesis experiment was improved to nearly 100%.
Similarly, the fourth, fifth, and sixth synthesis experiments were also performed. The reaction conversion rate to biphenyl was 98% at the 4th time, 94% at the 5th time, and 53% at the 6th time.

The reaction conversion rate of the target product obtained in the 0th to 6th synthesis experiments to biphenyl was evaluated by comparing the area (%) of the solution containing the product in “high performance liquid chromatography (HPLC)”. . The high performance liquid chromatograph (HPLC) used was manufactured by JASCO Corporation, and the measurement conditions were as follows.
Column: ODS-3
Mobile phase: acetonitrile / aqueous phosphoric acid solution = 80/20
Column temperature: 40 ° C
Flow rate: 1 ml / min

The results are shown in [Table 1] and [FIG. 1] below.

HPLC area (%) is a relative amount representing the percentage of the peak area of the target product in high performance liquid chromatography (high performance liquid chromatography).

Claims (7)

Use of a solid material composed of SiC as a Pd catalyst support in a transition metal catalyzed reaction carried out in the liquid phase in the presence of a catalyst containing palladium (Pd catalyst). The use according to claim 1, wherein the solid material made of SiC is β-SiC. The use according to claim 1 or 2, wherein the transition metal catalyzed reaction is a coupling reaction. The use according to claim 3, wherein the coupling reaction is a Suzuki-Miyaura coupling reaction. The organic boron compound and the organic halide are reacted in the presence of a palladium catalyst in the presence of a base to produce another organic compound in which the carbon in the organic boron compound is bonded to the carbon in the organic halide. In the Suzuki-Miyaura coupling reaction,
A method in which the palladium catalyst is supported on a solid material made of SiC. The so-called Suzuki-Miyaura coupling reaction in which an organic boron compound and an organic halide are reacted in the presence of a base to produce another organic compound in which the carbon in the organic boron compound and the carbon in the organic halide are combined. A palladium catalyst supported on a solid material made of SiC. A method for producing a supported palladium catalyst, comprising contacting a palladium catalyst used in a Suzuki-Miyaura coupling reaction with a solid material made of SiC, and fixing the palladium catalyst on the solid material made of SiC.

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