JP2018015713A - Catalyst-supporting particle for coupling reaction and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide catalyst-supporting particles for coupling reaction which obtains a coupling reaction product with high yield and is useful for synthesis of an organic compound.SOLUTION: Catalyst-supporting particles have the [1] to [3] structures. [1] The catalyst-supporting particles for coupling reaction are particles for cross-coupling which have (meth)acrylic resin particles and a transition metal catalyst supported by the particles, and are copolymerized with a monomer having two or more polymerizable double bonds. [2] The catalyst-supporting particles for coupling reaction, where a weight average particle diameter of the (meth)acrylic resin particles is 0.01-1,000 μm, preferably is 1-1,000 μm, more preferably is 10-1,000 μm, and particularly preferably is 50-1,000 μm, and is advantageous for collecting and recycling. [3] A method for producing catalyst-supporting particles for coupling reaction includes a step of carrying a transition metal catalyst by (meth)acrylic resin particles.SELECTED DRAWING: None

Description

  The present invention relates to a catalyst-supporting particle for coupling reaction and a method for producing the same.

  Conventionally, various catalysts have been used as organic compound synthesizing catalysts. However, industrial use is limited because the metal used as a catalyst (eg, palladium catalyst used in cross-coupling reaction) is expensive. There is a problem. In order to solve this problem, studies have been made such as (1) increasing the catalyst activity and exhibiting an effect by adding a small amount of catalyst, and (2) recovering and reusing the catalyst after use. In recent years, in the fields of pharmaceutical intermediates and electronic materials, the mixing of catalytic metals into products has been regarded as a problem, and (3) complications in the purification process of products and the use of organic solvents used in the purification process. Studies on the problem of increase and environmental pollution are being conducted.

  For (2) and (3), the use of heterogeneous catalysts has been studied. For example, a method is known in which a catalyst is supported on a carrier made of inorganic particles such as silica or zeolite, or organic particles such as polystyrene resin particles. However, a decrease in catalyst performance due to immobilization on the carrier is regarded as a problem. .

  For example, Patent Document 1 describes metal-supported fine particles in which metal fine particles are fixed to polymer fine particles. Although a catalyst is described as this use, it is not mentioned what kind of reaction the catalyst is.

  Patent Document 2 describes a carbon-carbon coupling reaction method using a catalyst composition in which a palladium catalyst is supported on a crosslinked organic polymer compound. As the organic polymer compound, a styrene polymer obtained by using a styrene monomer as a main component is disclosed in Examples.

Japanese Patent Laid-Open No. 04-285604 Japanese Patent No. 4497864

  The present inventors have examined a catalyst for coupling reaction useful for organic compound synthesis. That is, an object of the present invention is to provide a catalyst-supporting particle for coupling reaction, which can obtain a coupling reaction product with a high yield.

  The present inventors diligently studied to solve the above problems. As a result, in the coupling reaction, it was found that a heterogeneous catalyst using (meth) acrylic resin particles as a carrier can obtain a coupling reaction product in a higher yield than a commercially available heterogeneous catalyst. . That is, the present inventors have found that the above problems can be solved by catalyst-carrying particles having the following configuration, and have completed the present invention.

The present invention includes, for example, the following [1] to [4].
[1] Catalyst-supporting particles for coupling reaction, comprising (meth) acrylic resin particles and a transition metal catalyst supported on the particles.
[2] The catalyst-supporting particle for coupling reaction according to [1], which is for cross-coupling reaction.
[3] The catalyst-supporting particles for coupling reaction according to the above [1] or [2], wherein the (meth) acrylic resin particles have a weight average particle diameter of 0.01 to 1000 μm.
[4] A method for producing catalyst-supporting particles for coupling reaction, comprising a step of supporting a transition metal catalyst on (meth) acrylic resin particles.

  ADVANTAGE OF THE INVENTION According to this invention, the catalyst support particle | grains for coupling reaction which can obtain a coupling reaction product with a high yield can be provided.

  In this specification, “(meth) acryl” is used as a generic term for acrylic and methacrylic. The same applies to (meth) acrylic polymers and (meth) acrylates.

[Catalyst-supported particles for coupling reaction]
The catalyst-supporting particles for coupling reaction of the present invention (hereinafter also referred to as “catalyst particles”) have (meth) acrylic resin particles and a transition metal catalyst supported on the particles. Here, “supporting” may be an embodiment in which a transition metal catalyst is attached or immobilized on the surface of the resin particles, or an embodiment in which a transition metal catalyst is contained or immobilized in the resin particles. For example, the transition metal catalyst is complexed on the surface and / or inside of the resin particles.

  Examples of the coupling reaction include a homocoupling reaction and a cross coupling reaction. Specific examples of the coupling reaction include Suzuki-Miyaura coupling reaction, Mizorogi-Heck coupling reaction, Sonogashira coupling reaction, Negishi coupling reaction, Stille coupling reaction, Tsuji-trost coupling reaction, Kumada- Examples include Tamao coupling reaction, Buchwald-Hartwick coupling reaction, oxidative coupling reaction, and Ullmann coupling reaction.

  In the present invention, the reason why high reaction efficiency in the coupling reaction is obtained is not clear, but can be estimated as follows. By using (meth) acrylic resin particles as a catalyst carrier, substances such as reaction substrates and cocatalysts in the coupling reaction are attracted around the (meth) acrylic resin particles due to the polarity of the resin. It is presumed that the substance can be efficiently concentrated at the place where the substance exists, a reaction field having a high concentration of the substance is locally formed, and the reaction efficiency is improved.

  In addition, the catalyst particles of the present invention can be easily recovered and reused after use by setting the weight average particle diameter of the (meth) acrylic resin particles serving as a carrier to a range described below, particularly 50 μm or more.

<(Meth) acrylic resin particles>
In the present specification, the (meth) acrylic resin means a (meth) acrylic polymer formed from a raw material monomer (polymerizable monomer) in which the amount of (meth) acrylic ester is, for example, 51% by mass or more. In one embodiment, the amount of the (meth) acrylic acid ester in the raw material monomer is 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more. The (meth) acrylic resin particles are formed from a (meth) acrylic polymer.

  A (meth) acrylic polymer having a crosslinked structure may be formed by copolymerizing a monomer having two or more polymerizable double bonds together with a (meth) acrylic acid ester. Moreover, you may copolymerize other monomers other than the monomer of the said description which can be copolymerized with (meth) acrylic acid ester.

As (meth) acrylic acid ester, for example,
Methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acrylate, t-butyl (meth) acrylate, 2- Alkyl (meth) acrylates such as ethylhexyl (meth) acrylate, isooctyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate;
Alkoxyalkyl (meth) acrylates such as methoxymethyl (meth) acrylate and methoxyethyl (meth) acrylate;
Alicyclic group-containing (meth) acrylates such as cyclohexyl (meth) acrylate, isobornyl (meth) acrylate, and dicyclopentanyl (meth) acrylate;
Aromatic ring-containing (meth) acrylates such as phenyl (meth) acrylate, benzyl (meth) acrylate, and phenoxyethyl (meth) acrylate;
Ionic functional group-containing (meth) acrylates such as β-carboxyethyl (meth) acrylate, 5-carboxypentyl (meth) acrylate, mono (meth) acryloyloxyethyl ester succinate, ω-carboxypolycaprolactone mono ( Carboxyl group-containing (meth) acrylates such as (meth) acrylate;
Reactive functional group-containing (meth) acrylates other than ionic functional groups, for example, hydroxyalkyl (meta) such as 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate ), Hydroxyl group-containing (meth) acrylates such as polyalkylene glycol mono (meth) acrylates such as diethylene glycol mono (meth) acrylate and dipropylene glycol mono (meth) acrylate; dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) ) Acrylate, diethylaminoethyl (meth) acrylate, primary amino group-containing (meth) acrylate such as diethylaminopropyl (meth) acrylate; glycidyl (meth) acrylate (3,4-epoxycyclohexyl) methyl (meth) acrylate, glycidyl oxy (poly) alkylene glycol (meth) acrylate, epoxy group-containing (meth) acrylates such as methyl glycidyl (meth) acrylate;
Is mentioned.

The (meth) acrylic acid ester may be used alone or in combination of two or more.
In one embodiment, the total amount of alkyl (meth) acrylate, alkoxyalkyl (meth) acrylate and alicyclic group-containing (meth) acrylate in 100% by mass of (meth) acrylic acid ester is 10.0 to 99.9. The total amount of the ionic functional group-containing (meth) acrylate and the reactive functional group-containing (meth) acrylate is 0.1 to 90% by mass, or 1 to 70% by mass. It is.

Examples of the monomer having two or more polymerizable double bonds include polyfunctional (meth) acrylic acid esters and divinylbenzene.
As polyfunctional (meth) acrylic acid ester, for example,
Di, tri or polyalkylene glycol-di (meth) acrylates such as diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, polytetraethylene glycol di (meth) acrylate;
Ethylene glycol di (meth) acrylate, 1,4-butanediol di (meth) acrylate, neopentyl glycol di (meth) acrylate, 3-methyl-1,5-pentanediol di (meth) acrylate, 1,6-hexane Alkanediol di (meth) acrylates such as diol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, tricyclodecane dimethylol di (meth) acrylate;
Glycerin tri (meth) acrylate, trimethylolpropane tri (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, pentaerythritol tri (meth) acrylate, pentaerythritol tetra (meth) acrylate, dipentaerythritol penta (meth) acrylate, Dipentaerythritol hexa (meth) acrylate, glycerol alkylene oxide modified tri (meth) acrylate, trimethylolpropane alkylene oxide modified tri (meth) acrylate, pentaerythritol alkylene oxide modified tri (meth) acrylate, pentaerythritol alkylene oxide modified tetra (meth) ) Acrylate, dipentaerythritol alkylene oxide modified hexa (meth) a Relate, dipentaerythritol caprolactone-modified hexa (meth) acrylate, tris (2-hydroxyethyl) isocyanurate tri (meth) tri- or more functional polyol poly (meth) acrylates such as acrylate;
Is mentioned.

Monomers having two or more polymerizable double bonds may be used alone or in combination of two or more.
The amount of the monomer having two or more polymerizable double bonds is preferably 0.01 to 20 parts by mass, more preferably 0.1 to 5 parts by mass with respect to 100 parts by mass of the (meth) acrylic acid ester. . By forming the crosslinked structure, it is possible to prevent the catalyst particles from being dissolved in the reaction solvent in the coupling reaction and making it difficult to recover and reuse them, and to increase the heat resistance of the catalyst particles.

As other copolymerizable monomers, for example,
Unsaturated carboxylic acids such as (meth) acrylic acid, α-ethyl (meth) acrylic acid, crotonic acid, α-methylcrotonic acid, α-ethylcrotonic acid, isocrotonic acid, tiglic acid, angelic acid, etc. Monocarboxylic acids; unsaturated aliphatic dicarboxylic acids such as maleic acid, fumaric acid, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, hydromuconic acid;
Styrene monomers (styrene and its derivatives), for example, styrene; alkyl such as methyl styrene, dimethyl styrene, trimethyl styrene, ethyl styrene, diethyl styrene, triethyl styrene, propyl styrene, butyl styrene, hexyl styrene, heptyl styrene, octyl styrene Halogenated styrene such as fluorostyrene, chlorostyrene, bromostyrene, dibromostyrene, iodostyrene, chloromethylstyrene;
Vinyl acetate;
Is mentioned.
The other copolymerizable monomers may be used alone or in combination of two or more.

<Method for producing (meth) acrylic resin particles>
(Meth) acrylic resin particles are, for example, polymerization methods in an aqueous medium such as suspension polymerization, emulsion polymerization, soap-free emulsion polymerization, seed polymerization; other polymerization such as solution polymerization, precipitation polymerization, dispersion polymerization, bulk polymerization, etc. It can be prepared by a method. In bulk polymerization or the like, resin particles can be prepared by crushing the obtained bulk resin mass and classifying it as necessary. In view of recovery and reusability, resin particles having a weight average particle diameter of about 100 μm are suitable for use as catalyst support particles, and among these, suspension polymerization is preferred.

  Examples of the polymerization initiator that can be used in suspension polymerization and the other polymerization methods include peroxides such as benzoyl peroxide and lauroyl peroxide; azo compounds such as azobisisobutyronitrile, and emulsification. Examples of the polymerization initiator that can be used for polymerization and soap-free emulsion polymerization include persulfates such as potassium persulfate and ammonium persulfate. A polymerization initiator may be used independently and may use 2 or more types together. The usage-amount of a polymerization initiator is 0.1-5 mass parts normally with respect to 100 mass parts of polymerizable monomers, Preferably it is 0.3-2 mass parts.

  Examples of the aqueous medium that can be used for the polymerization include water and a mixture of water and a hydrophilic organic solvent. Examples of water include purified water (eg, ion exchange water, distilled water), ground water, and tap water. Examples of the hydrophilic organic solvent include lower alcohols such as methanol, ethanol and isopropanol; polyhydric alcohols such as ethylene glycol, propylene glycol, butanediol, diethylene glycol and triethylene glycol; cellosolves such as methyl cellosolve and ethyl cellosolve: acetone Ketones such as tetrahydrofuran; ethers such as tetrahydrofuran; and esters such as methyl formate. A hydrophilic organic solvent may be used independently and may use 2 or more types together. The usage-amount of a hydrophilic organic solvent is normally 10 mass parts or less with respect to 100 mass parts of water.

  Examples of the suspension stabilizer that can be used for suspension polymerization include polyvinyl alcohols such as partially saponified polyvinyl alcohol, fully saponified polyvinyl alcohol, and modified polyvinyl alcohol; hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose salt, and the like. A cellulose derivative is mentioned. A suspension stabilizer may be used independently and may use 2 or more types together. The usage-amount of a suspension stabilizer is 0.01-20 mass parts normally with respect to 100 mass parts of polymerizable monomers, Preferably it is 0.1-5 mass parts.

  Below, the suspension polymerization method which is a preferable polymerization method is demonstrated. (Meth) acrylic resin particles, for example, a polymerizable monomer (raw material monomer) containing (meth) acrylic acid ester is suspended in an aqueous medium in the presence of a polymerization initiator and, if necessary, a suspension stabilizer. It is preferable to obtain by polymerization. For example, a medium in which a suspension stabilizer is dissolved in an aqueous medium is prepared, the obtained medium and a liquid containing a polymerizable monomer and a polymerization initiator are mixed with stirring, and further suspended using a device such as a homogenizer. Prepare a suspension. By adjusting the shearing force by changing the stirring speed of the apparatus, it is possible to adjust the monomer droplets to a desired size.

In suspension polymerization, the polymerization temperature is usually 50 to 90 ° C., preferably 60 to 80 ° C., and the polymerization time is usually 1 to 24 hours, preferably 1 to 10 hours.
After completion of the suspension polymerization, the resin particles are separated from the aqueous medium by a solid-liquid separation method such as filtration or centrifugation. If necessary, components such as a suspension stabilizer are further removed in a washing step and dried. As described above, (meth) acrylic resin particles can be obtained by suspension polymerization.

<Polarity design of (meth) acrylic resin particles>
In the present invention, since a (meth) acrylic resin is used for the catalyst carrier, the introduction of functional groups such as ionic functional groups, hydroxyl groups, and amino groups, and the amount of introduction thereof, using commercially available (meth) acrylic monomers. There is an advantage that it can be adjusted easily and appropriately. Moreover, it is possible to easily fix the transition metal catalyst to the resin particles by appropriately selecting the functional group, and it is possible to design the catalyst according to the coupling reaction system (reaction medium, reaction substrate).

  When the (meth) acrylic polymer has an ionic functional group (eg, carboxyl group) or a reactive functional group (eg, hydroxyl group, amino group, epoxy group), it reacts with the ionic functional group or reactive functional group. A compound having a functional group that can be reacted with the polymer may adjust the polarity of the (meth) acrylic resin particles to facilitate fixing of the transition metal catalyst to the resin particles. Examples of the functional group of the polymer include an ionic functional group derived from the ionic functional group-containing (meth) acrylate and a reactive functional group derived from the reactive functional group-containing (meth) acrylate. .

  When the reactive functional group is an epoxy group, examples of the compound having a functional group capable of reacting with the reactive functional group include an amine compound, specifically, methylamine, ethylamine, propylamine, butylamine, ethanol. Examples include primary amines such as amines; secondary amines such as dimethylamine, diethylamine, dibutylamine, methylethylamine, diethanolamine, dipropanolamine, N-methylethanolamine, and N-ethylethanolamine. An amine compound may be used independently and may use 2 or more types together. Here, the epoxy group is ring-opened with an amine compound, and a hydroxyl group and an amino group are introduced into the resin particles. The usage-amount of an amine compound with respect to 1 mol of epoxy groups of a (meth) acrylic polymer is 1-10 mol normally, Preferably it is 1-5 mol. The reaction can be performed, for example, at 10 to 90 ° C. for 1 to 48 hours.

  In the present invention, by introducing an ionic functional group into the (meth) acrylic polymer, the polarity of the (meth) acrylic resin particles may be adjusted, and the transition metal catalyst may be easily fixed to the resin particles. Examples of the ionic functional group include cationic functional groups such as amino group hydrochloride, imino group, quaternary ammonium salt, and quaternary phosphonium salt; carboxyl group, sulfonic acid group, sulfuric acid group, phosphoric acid group, Anionic functional groups such as boronic acid groups can be mentioned.

As a method for introducing an ionic functional group into the polymer, for example,
(1) A method of preparing a (meth) acrylic polymer having an ionic functional group by polymerizing a raw material monomer containing an ionic functional group-containing (meth) acrylate;
(2) A precursor functional polymer having a reactive functional group is prepared by polymerizing a raw material monomer containing a reactive functional group-containing (meth) acrylate other than an ionic functional group, and the reactive functional group possessed by the precursor polymer. A compound having a functional group capable of forming or introducing an ionic functional group (hereinafter also referred to as “compound M”) by reacting with the precursor polymer is reacted with a (meth) acrylic polymer having an ionic functional group. A method of preparing a coalescence;
(3) A method for introducing a carboxyl group by polymerizing a raw material monomer containing (meth) acrylic acid ester and then hydrolyzing the ester part of poly (meth) acrylic acid ester obtained under alkaline conditions (for example, JP 2011-126979 gazette);
(4) A method of forming a resin particle made of a (meth) acrylic polymer having no ionic functional group, and thereafter performing a treatment for imparting surface charges such as plasma treatment, ultraviolet irradiation treatment and ozone treatment;
Is mentioned.

  In the method (2), examples of the compound M include a compound M1 having a functional group capable of forming an ionic functional group by reacting with a reactive functional group of the precursor polymer, and a reactive function of the precursor polymer. And a compound M2 having a functional group capable of reacting with a group to form a chemical bond and an ionic functional group. The compound M is appropriately selected according to the reactive functional group that the precursor polymer has.

  When the reactive functional group of the precursor polymer is an epoxy group, examples of the compound M include a tertiary amine compound, a compound M1 such as sodium bisulfite, and a compound M2 such as oxalic acid, succinic acid, and adipic acid. Can be mentioned. When the reactive functional group of the precursor polymer is a tertiary amino group, examples of the compound M include known quaternizing agents.

Hereinafter, the (meth) acrylic polymer having a quaternary ammonium salt will be described.
A (meth) acrylic polymer having a quaternary ammonium salt can be obtained by converting a part or all of the amino group of a precursor polymer having a tertiary amino group into a quaternary ammonium salt. . For example, a precursor polymer having a tertiary amino group is reacted with a known quaternizing agent in a solvent or without a solvent.

  Examples of the quaternizing agent include organic halides, specifically, benzyl halides such as benzyl chloride, benzyl bromide and benzyl iodide; methyl chloride, ethyl chloride, methyl bromide and methyl iodide. And the like. A quaternizing agent may be used independently and may use 2 or more types together.

  In the formation reaction of the quaternary ammonium salt, the molar ratio of the amino group in the precursor polymer to the quaternizing agent (quaternizing agent / amino group) is preferably 0.1 to 5. The reaction can be performed, for example, at 20 to 90 ° C. over 1 to 35 hours.

  The (meth) acrylic polymer having a quaternary ammonium salt can also be obtained by reacting a precursor polymer having an epoxy group with a tertiary amine compound. In this method, part or all of the epoxy group is opened with a tertiary amine compound to form a quaternary ammonium salt.

Examples of the tertiary amine compound include trimethylamine, triethylamine, tributylamine, trioctylamine, N-methylmorpholine, N-ethylmorpholine, N, N-dimethylethanolamine, N, N-diethylethanolamine, N, N -Dibutylethanolamine, N-methyldiethanolamine, Nn-butyldiethanolamine, Nt-butyldiethanolamine, N, N-diethylisopropanolamine, 1-methylimidazole may be mentioned. A tertiary amine compound may be used independently and may use 2 or more types together.
In the ammonium salt formation reaction, the molar ratio of the epoxy group in the precursor polymer to the tertiary amine compound (tertiary amine / epoxy group) is preferably 0.1-10. The said reaction can be performed over 0.5 to 6 hours at 40-90 degreeC, for example.

<Configuration of (meth) acrylic resin particles>
The shape of the (meth) acrylic resin particles is not particularly limited, and may be spherical or an irregular shape having anisotropy, may be porous, and may be hollow. However, it is preferably spherical.

  The weight average particle diameter of the (meth) acrylic resin particles is preferably 0.01 to 1000 μm, more preferably 1 to 1000 μm, still more preferably 10 to 1000 μm, and particularly preferably 50 to 1000 μm. A weight average particle diameter of 50 μm or more is preferable in that the catalyst particles can be easily recovered and reused and the handling property is excellent.

The weight average particle diameter can be measured using a laser diffraction particle size distribution analyzer.
Moreover, as described above, the catalyst performance in the coupling reaction can be improved by adjusting the polarity of the resin particles with respect to the polarity of the coupling reaction system, for example, the polarity of the reaction substrate or the reaction medium.

  Moreover, the resin particle which has swelling property with respect to the solvent used by coupling reaction is preferable. In this case, the reaction easily occurs not only on the particle surface but also inside, and the reaction efficiency can be increased. “Swellability” means, for example, that after 5 g of resin particles are put in a transparent cylindrical container having an inner diameter of 1 cm and tapped well, the particle height is set to Ha, and a sufficient amount of a solvent used for the coupling reaction is added thereto and stirred well. It means that the ratio (Hb / Ha) when the particle height Hb settled in the transparent cylindrical container after standing for 24 hours is 1 or more.

<Catalyst loading on (meth) acrylic resin particles>
The method for supporting the transition metal catalyst, which is a coupling reaction catalyst, on the (meth) acrylic resin particles is not particularly limited. For example, a liquid mixture of a dispersion medium, resin particles, and a transition metal catalyst is usually 1 to 48 hours, preferably 1 on the condition that the liquid temperature of the liquid mixture is usually 10 to 90 ° C, preferably 10 to 50 ° C. Stir for ~ 35 hours. Subsequently, the catalyst-carrying particles are separated from the dispersion medium by a solid-liquid separation method such as filtration or centrifugation. Purify and / or dry as necessary.

  Examples of the dispersion medium include aromatic hydrocarbons such as toluene and xylene; ethers such as diethyl ether, dibutyl ether and tetrahydrofuran; aliphatic saturated hydrocarbons such as pentane and hexane; alcohols such as methanol and ethanol Organic solvents; and the above-mentioned aqueous medium. A dispersion medium may be used independently and may use 2 or more types together.

  The blending amount or loading amount of the transition metal is usually 0.001 to 1 mole, preferably 0.01 to 1 mole of the functional group interacting with the introduced transition metal in the (meth) acrylic resin particles. -1 mol, more preferably 0.1-1 mol. Moreover, the compounding quantity or carrying | support amount of a transition metal catalyst is 0.01-80 mass parts normally with respect to 100 mass parts of (meth) acrylic resin particles, Preferably it is 1-50 mass parts.

  The transition metal is preferably a late transition metal. The post-period transition metal refers to a group 8 to 11 element in the periodic table. Among the late transition metal catalysts, transition metal catalysts containing palladium, nickel, iron or copper are preferable. A transition metal catalyst containing ruthenium, rhodium or iridium can also be used as the late transition metal catalyst.

When the transition metal catalyst is a transition metal complex, examples of the organic ligand include triphenylphosphine (PPh ₃ ), 1,1′-bis (diphenylphosphino) ferrocene (dppf), and tri-tert-butylphosphine. Organic phosphine ligands such as (P (t-Bu) ₃ ), tricyclohexylphosphine (P (Cy) ₃ ), tri (o-tolyl) phosphine (P (o-tol) ₃ ), allyl, Examples include dibenzylideneacetone (dba), acetylacetone (acac), acetic acid ligand (OAc), and trifluoroacetic acid ligand (TFA).

Examples of the palladium catalyst include Pd (PPh ₃ ) ₄ , Pd (PPh ₃ ) ₂ Cl ₂ , PdCl ₂ (dppf), PdCl ₂ (dppf) CH ₂ Cl ₂ , Pd (P (t-Bu) ₃ ) _4. Pd (P (Cy) ₃ ) ₂ Cl ₂ , Pd (P (o-tol) ₃ ) ₄ , Pd (P (o-tol) ₃ ) ₂ Cl _{2 and} other palladium phosphine complexes; Pd (allyl) Cl ₂ , [Pd (allyl) Cl] 2 or the like palladium allyl _{complex; Pd 2 (dba) 3,} Pd 2 (dba) 3 CHCl 3, Pd (dba) 2, Pd (acac) 2, Pd (OAc) 2, Pd Other palladium complexes such as (TFA) ₂ ; PdCl ₂ , PdBr _{2 and} other palladium salts. Among these, a palladium complex is preferable and a palladium allyl complex is more preferable.

Examples of the ruthenium catalyst include potassium perruthenate, perruthenic acid (tetrapropylammonium), and perruthenic acid (tetrabutylammonium).
Specific examples of the palladium catalyst and ruthenium catalyst other than the above and specific examples of other catalysts include, for example, the catalysts described in International Publication No. 2013/065855.

<Uses of (meth) acrylic resin particles>
Since the catalyst particles of the present invention have the above configuration, they exhibit high activity as a coupling reaction catalyst. Examples of the coupling reaction include a cross coupling reaction and a homocoupling reaction.

As the cross-coupling reaction, for example,
Suzuki-Miyaura coupling reaction, that is, a reaction in which an organic boron compound and an organic halide are cross-coupled under a basic condition using a transition metal such as palladium as a catalyst;
-Mizorogi-Heck coupling reaction, that is, a reaction in which a terminal alkene and an aryl halide are cross-coupled under a basic condition using a transition metal such as palladium as a catalyst to synthesize an alkenyl aryl compound;
-Sonogashira coupling reaction, that is, a reaction in which a terminal alkyne and an aryl halide are cross-coupled under a basic condition using a transition metal such as palladium as a catalyst to synthesize an alkynyl aryl compound;
-Negishi coupling reaction, that is, a reaction in which an organozinc compound and an organic halide are cross-coupled using a transition metal such as palladium or nickel as a catalyst;
-Stille coupling reaction, that is, a reaction in which an organotin compound and an organic halide are cross-coupled using a transition metal such as palladium as a catalyst;
・ Coupling of allylic alkylation products by cross-coupling allylic esters with organic nucleophiles under basic conditions using a transition metal such as palladium as a catalyst. reaction;
-Kumada-Tamao coupling reaction, that is, a reaction in which a Grignard reagent and an organic halide are cross-coupled using a transition metal such as nickel or palladium as a catalyst;
-Buchwald-Hartwick coupling reaction, that is, using a transition metal such as palladium as a catalyst, an aryl halide or an aryl ether is synthesized by cross-coupling an aryl halide and an amine or alcohol under basic conditions. reaction;
Is mentioned.

Examples of homocoupling reactions include:
An oxidative coupling reaction, that is, a method of synthesizing a biaryl compound by homo-coupling hydroxyaryl using a transition metal such as ruthenium as a catalyst and molecular oxygen as an oxidizing agent;
-Ullmann coupling reaction, that is, a reaction in which a transition metal such as copper or nickel is used as a catalyst to homocouple aryl halide to synthesize a bi-hydroxyaryl compound;
Is mentioned.

  The catalyst particles of the present invention are suitable as a cross-coupling reaction catalyst, and are particularly suitable as a Suzuki-Miyaura coupling reaction catalyst. The Suzuki-Miyaura coupling reaction will be described below.

As a transition metal catalyst, the palladium catalyst mentioned above is mentioned, for example.
Examples of the organic boron compound include aryl boronic acids such as phenyl boronic acid, phenylene diboronic acid, naphthalene boronic acid, naphthalene diboronic acid, biphenyl boronic acid, and biphenyl diboronic acid. The organic boron compound usually has 6 to 30 carbon atoms, and the number of boronic acid groups in one molecule is usually 3 or less.

  Examples of the halogen atom in the organic halide include chlorine, iodine, and bromine. Examples of the organic halide include aryl halides such as benzene, naphthalene and biphenyl substituted with the halogen atom. The number of carbon atoms of the organic halide is usually 6 to 30, and the number of halogens in one molecule is usually 3 or less.

  In the aryl boronic acid and aryl halide, one or more of the hydrogen atoms on the aromatic ring may be substituted with a substituent. Examples of the substituent include an alkyl group, an aryl group, an alkoxy group, an alkoxycarbonyl group, a halogenated alkyl group, a halogenated aryl group, a halogenated alkoxy group, a vinyl group, a hydroxyl group, a carboxyl group, an aldehyde group, an acyl group, and an amino group. Group, cyano group, nitro group, carboxyalkyl group, hydroxyalkyl group, aminoalkyl group. Examples of such arylboronic acids include ethylphenylboronic acid; examples of aryl halides include p-tert-butylbromobenzene, p-bromoanisole, p-bromobenzonitrile, p-bromobenzoate methyl, p- And ethyl bromobenzoate.

  The Suzuki-Miyaura coupling reaction is performed under basic conditions. Examples of the base include an organic base and an inorganic base, and an inorganic base is preferable. For example, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, sodium phosphate , Potassium phosphate and sodium acetate. A base may be used independently and may use 2 or more types together.

  The amount of the catalyst particles is such that the amount of the transition metal supported on the catalyst particles is usually 0.0001 to 50 mol%, preferably 0.001 to 10 mol% with respect to the amount of the organic halide. It is. Moreover, about each equivalent ratio, with respect to the organic halide, the organic boron compound is usually 0.5 to 3 equivalents, preferably 1 to 3 equivalents, and the base is usually 0.5 to 5 equivalents, preferably 1 to 3 equivalents.

  The reaction temperature in the Suzuki-Miyaura coupling reaction is usually 0 to 200 ° C., preferably 25 to 150 ° C., and the reaction time is usually 0.01 to 100 hours, preferably 0.1 to 50 hours. .

  In the Suzuki-Miyaura coupling reaction, a solvent may be used. Examples of the solvent include aromatic hydrocarbons such as toluene and xylene; ethers such as diethyl ether, dibutyl ether and tetrahydrofuran; aliphatic saturated hydrocarbons such as pentane and hexane; alcohols such as methanol and ethanol; Organic solvent; the aqueous medium mentioned above is mentioned. A solvent may be used independently and may use 2 or more types together.

  By using the catalyst particles of the present invention, a biaryl compound can be produced in a high yield by a cross-coupling reaction between an aryl boronic acid and an aryl halide in the presence of a base.

  Further, the catalyst particles of the present invention are suitable as a catalyst for oxidative coupling reaction. In the reaction, examples of the transition metal catalyst include the ruthenium catalyst described above, and examples of the hydroxyaryl include phenol, Examples thereof include naphthol and compounds having the above-described substituents on these aromatic rings. In the above reaction, the base and the solvent described above in the description of the Suzuki-Miyaura coupling reaction may be used.

  The amount of the catalyst particles is an amount such that the amount of transition metal supported on the catalyst particles is usually 0.1 to 50 mol%, preferably 1 to 10 mol%, based on the amount of hydroxyaryl. Moreover, about each equivalent ratio, a base is 0.1-5 equivalent normally with respect to hydroxyaryl, Preferably it is 0.2-1 equivalent.

The reaction temperature in the oxidative coupling reaction is usually 20 to 150 ° C., preferably 60 to 100 ° C., and the reaction time is usually 1 to 50 hours, preferably 1 to 30 hours.
By using the catalyst particles of the present invention, a hydroxyaryl can be homocoupled to produce a bi-hydroxyaryl compound in high yield.

EXAMPLES Hereinafter, although this invention is demonstrated further more concretely based on an Example, this invention is not limited to these Examples.
[Average particle diameter of resin particles]
The weight average particle diameter of the resin particles was measured using a laser diffraction particle size distribution measuring apparatus (manufactured by Sysmex Corporation, model: Mastersizer-2000).

[Synthesis Example 1] Synthesis of isobutyl methacrylate methacrylic resin particles A (iBMA) 49g, glycidyl methacrylate (GMA) 50 g, and a mixture of ethylene glycol dimethacrylate (EGDMA) 1 g, was dissolved lauroyl peroxide 0.5g thereto . 300 g of ion-exchanged water in which 2 g of partially saponified polyvinyl alcohol was dissolved was added to this liquid, and suspension polymerization was carried out under a nitrogen atmosphere at 70 ° C. for 3 hours with stirring to obtain methacrylic resin particles having a weight average particle diameter of 100 μm. A dispersed methacrylic resin particle dispersion was obtained. This dispersion was subjected to solid-liquid separation and water washing three times with 200 mesh, and the separated methacrylic resin particles were put in a dryer at 50 ° C. and dried.

  To 3 g of the resulting methacrylic resin particles, 27 mL of water and 3 g of a 50% by weight dimethylamine aqueous solution were added and reacted at 80 ° C. for 7 hours. Then, filtration through a glass filter and washing with water were repeated 5 times, followed by vacuum drying. As a result, catalyst-supporting methacrylic resin particles A were obtained.

[Synthesis Example 2] 13 g of toluene and [PdCl (C ₃ H ₅ )] ₂ were added to 2 g of supported methacrylic resin particles A of palladium (Pd) complex so that Pd: N = 1: 6 (molar ratio). The mixture was stirred at room temperature for 20 hours to allow the methacrylic resin particles A to carry the Pd complex. The obtained product was purified by performing filtration through a glass filter and washing with toluene twice, followed by vacuum drying to obtain methacrylic resin particles carrying Pd complexes (Pd complex-carrying methacrylic resin particles). It was.

[Example 1] Cross-coupling reaction To 3 mmol ethyl p-bromobenzoate and ethyl p-bromobenzoate, 1.05 equivalents of phenylboronic acid, 2 equivalents of potassium carbonate, and 3 mL of toluene were added for further synthesis. The Pd complex-supported methacrylic resin particles obtained in Example 2 were added so that the amount of Pd was 0.05 mol% with respect to the amount of ethyl p-bromobenzoate, and reacted at 100 ° C. for 1 hour. The product biaryl compound was obtained in a yield of 99%.

[Example 2] Cross- coupling reaction The reaction was carried out in the same manner as in Example 1 except that the reaction temperature of the coupling reaction was 70 ° C. The coupling reaction product was obtained with a yield of 82%.

[Comparative Example 1] Instead of the Pd complex-supported methacrylic resin particles obtained in the cross-coupling reaction synthesis example 2, a commercially available catalyst-supporting polyethylene fiber (product name "FibreCat 1001," manufactured by Johnson Matthey; FiberCat is a registered trademark) Was carried out in the same manner as in Example 2 except that the amount of Pd was 0.05 mol% with respect to the amount of ethyl p-bromobenzoate. The coupling reaction product was obtained with a yield of 21%.

[Comparative Example 2] Instead of the Pd complex-supported methacrylic resin particles obtained in Cross-coupling reaction synthesis example 2, commercially available catalyst-supported polystyrene fine particles (product name “PS-PPh ₃ -Pd”, manufactured by Biotage Japan) were used. The same procedure as in Example 2 was carried out except that the amount of Pd was 0.05 mol% relative to the amount of ethyl p-bromobenzoate. The coupling reaction product was obtained with a yield of 73%.

[Synthesis Example 3] Synthesis of methacrylic resin particles B 69 g of iBMA, 30 g of dimethylaminoethyl methacrylate, and 1 g of EGDMA were mixed, and 1 g of lauroyl peroxide was dissolved therein. To this solution was added 300 g of ion-exchanged water in which 0.25 g of partially saponified polyvinyl alcohol was dissolved, and suspension polymerization was carried out under a nitrogen atmosphere at 70 ° C. for 3 hours with stirring, and a methacrylic resin having a weight average particle size of 100 μm. A methacrylic resin particle dispersion in which particles were dispersed was obtained. This dispersion was subjected to solid-liquid separation and water washing three times with 200 mesh, and the separated methacrylic resin particles were put in a dryer at 50 ° C. and dried.

  2.06 g of the obtained methacrylic resin particles and 630 mg of benzyl bromide were added to 20 mL of toluene and reacted at 70 ° C. for 27 hours, followed by filtration with a glass filter, washing with toluene, and washing with acetone. Resin particles B were obtained.

[Synthesis Example 4] 30 mL of water and 134 mg of KRuO ₄ were added to 504 mg of ruthenium (Ru) catalyst-supported methacrylic resin particles B, and the mixture was stirred at room temperature for 29 hours to support the methacrylic resin particles B with the Ru catalyst. The obtained product was purified by carrying out filtration through a glass filter and washing with water and acetone twice, and then vacuum-dried to provide methacrylic resin particles carrying a Ru catalyst (Ru catalyst-supporting methacrylic resin particles). Got.

[Example 3] To 6 mL of homocoupling reaction water, 1.21 mmol of 2-naphthol and 0.5 equivalent of sodium hydrogen carbonate with respect to 2-naphthol were added, and the Ru catalyst-supported methacryl obtained in Synthesis Example 4 was further added. When the resin particles were added so that the Ru amount was 5 mol% with respect to the 2-naphthol amount and reacted at 80 ° C. for 3 hours in the presence of oxygen, the coupling reaction product 1,1′-bi-2 was obtained. -Naphthol was obtained with a yield of 48%.

[Comparative Example 3] Instead of the Ru catalyst-carrying methacrylic resin particles obtained in Homocoupling Reaction Synthesis Example 4, KRuO ₄ was added except that the Ru amount was 5 mol% with respect to the 2-naphthol amount. Was carried out in the same manner as in Example 3. The coupling reaction product was obtained with a yield of 22%.

Claims (4)

(Meth) acrylic resin particles;
A catalyst-supporting particle for coupling reaction, comprising a transition metal catalyst supported on the particle.   The catalyst-supporting particle for coupling reaction according to claim 1, which is for cross-coupling reaction.   The catalyst-carrying particles for coupling reaction according to claim 1 or 2, wherein the (meth) acrylic resin particles have a weight average particle diameter of 0.01 to 1000 µm.   A method for producing catalyst-supporting particles for coupling reaction, comprising a step of supporting a transition metal catalyst on (meth) acrylic resin particles.