Catalyst, method for producing the same, and method for producing compounds using the catalyst.

Abstract

This invention provides a technology to suppress the contamination of the product with catalyst-derived components when used in catalytic reactions. [Solution] A specific catalyst is used in organic synthesis reactions that utilize heterogeneous palladium (Pd) catalysts. The catalyst is composed of a Pd mononuclear complex supported on an inorganic support, the Pd mononuclear complex having a Pd atom and a single phosphate ligand coordinately bonded to it, the single phosphate ligand having a phosphorus atom coordinately bonded to the Pd atom and an aromatic ring.

Description

Technical Field

[0001] The present invention relates to a catalyst, a method for producing the same, and a method for producing a compound using the catalyst. Background Art

[0002] Organic synthesis reactions catalyzed by metal complexes have long been known, and reactions for forming carbon-carbon bonds (C-C bonds) using various methods have been reported. Among these, the Migita-Kosugi-Stille cross-coupling reaction is a method of performing a cross-coupling reaction between an organic halide and an organotin compound using a palladium catalyst. Since this coupling reaction can be carried out under neutral conditions and proceeds under relatively mild reaction conditions, it is frequently used in the final step of synthesizing compounds having complex structures including natural products, and is therefore extremely useful.

[0003] In general, homogeneous palladium catalysts are widely used mainly in cross-coupling reactions (see, for example, Non-Patent Document 1). In principle, homogeneous catalysts cannot be reused, and an operation to remove the catalyst from the product is required after completion of the reaction. Moreover, if the removal of the catalyst is insufficient, residual metal derived from the catalyst may be mixed into the product and affect the properties of the product. It is known that synthesis using homogeneous catalysts has various problems as described above.

[0004] To solve these problems, attempts have been made to support a palladium complex on a solid support to allow it to function as a heterogeneous catalyst (see, for example, Non-Patent Document 2).

[0005] Methods for immobilizing palladium complexes include covalent bonding of the ligand's functional groups to the support surface, or bringing the ligand's functional groups to the support surface in close proximity through intermolecular interactions such as ionic or hydrogen bonding. These methods require the support and the catalyst complex to be chemically modified beforehand in order to support the catalyst on the support surface. Therefore, this can lead to increased costs in catalyst production, which can limit their industrial use. Furthermore, even if a support complex is devised by mimicking an efficient homogeneous palladium complex, it is necessary to introduce functional groups into the complex for bonding to the support, which can limit the ability to optimize the complex's electronic state for the reaction.

[0006] In palladium-catalyzed reactions, examples of support that do not require chemical modification of the support or complex include the use of activated carbon as a support. Such catalysts have been reported to be useful in Suzuki-Miyaura coupling reactions using [Pd(acac)2] complexes, or carbonylation reactions using [Pd(xantphos)Cl2] complexes (see, for example, Non-Patent Documents 3 and 4). In these prior examples, attempts were made to mix the complex solution with activated carbon, dry the solvent, and use the resulting catalyst as is. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Norio Miyaura and Akira Suzuki, "Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds"Chem.Rev. 1995, 95, p.2457-2483 [Non-Patent Document 2] Bo Zhang and Joost NH Reek, "Supramolecular Strategies for the Recycling of Homogeneous Catalysts" Chem.Asian J. 2021, 16, p.3851-3863 [Non-Patent Document 3] Satoshi Inagaki, et al., "Selective Heating of Pd-Modified Ordered Mesoporous Carbon CMK-3 by Microwave Irradiation" Bull.Chem.Soc.Jpn., 84, 10, 2011, p.1136-1143 [Non-Patent Document 4] Ind.Eng.Chem.Res.58(2019)p.22951-22957 [Overview of the project] [Problems that the invention aims to solve]

[0008] The present inventors prepared the catalysts described in Non-Patent Documents 3 and 4 by supporting a homogeneous palladium complex on activated carbon, and found that approximately half of the homogeneous catalyst used remained unsupported on the activated carbon. If used as a catalyst in this state, contamination of the product with components derived from the complex is unavoidable. Furthermore, the amount of homogeneous catalyst supported on the activated carbon is low, requiring the use of a large amount of activated carbon when performing coupling reactions, etc. Thus, in the conventional technology, there is room for improvement in terms of suppressing the contamination of the product with catalyst-derived components when used in catalytic reactions, due to the low support rate of the palladium complex.

[0009] One aspect of the present invention aims to provide a technique for suppressing the contamination of the product with palladium when used in a catalytic reaction. [Means for solving the problem]

[0010] The inventors, through diligent research, discovered that a catalyst containing an inorganic support on which a homogeneous palladium complex having a specific ligand is adsorbed can solve the above problems, and thus completed the present invention. That is, the present invention provides the following.

[0011] [1] A catalyst comprising an inorganic support and a palladium mononuclear complex supported on the inorganic support, wherein the palladium mononuclear complex comprises a palladium atom and a monophosphate ligand coordinately bonded to the palladium atom, the monophosphate ligand comprises a phosphorus atom and an aromatic ring, the phosphorus atom being coordinately bonded to the palladium atom.

[0012] [2] The catalyst according to [1], wherein the catalyst is for the synthesis of polymer compounds.

[0013] [3] The catalyst according to [1] or [2], wherein the inorganic support is activated carbon.

[0014] A method for producing a compound, comprising the step of synthesizing a π-conjugated functional organic compound in the presence of a catalyst described in any of [4], [1], to [3].

[0015] [5] The method for producing the compound according to [4], wherein the synthesis step is a step of synthesizing the compound by a Migita-Kosugi-Stillcross coupling reaction in the presence of the catalyst.

[0016] A method for producing a catalyst according to any one of [6], [1] to [3], comprising the step of bringing the inorganic support into solid-liquid contact with a solution of the palladium mononuclear complex.

[0017] [7] The method for producing the catalyst according to [6], wherein the monolithic monolithic ligand further comprises an alkyl group.

[0018] [8] A method for producing a catalyst according to [6] or [7], further comprising the step of washing the inorganic support after the solid-liquid contact step. [Effects of the Invention]

[0019] According to the present invention, contamination of a product with palladium can be suppressed when used in a catalytic reaction. MODE FOR CARRYING OUT THE INVENTION

[0020] The present inventors mixed an inorganic support and a homogeneous palladium complex in a solvent, and after drying the solvent, performed a synthesis reaction using the supported catalyst. As a result, they found that the amount of palladium leached from the support can be reduced, and consequently the amount of residual palladium in the product is decreased. Hereinafter, embodiments of the present invention (which may be referred to as the present embodiment hereinafter) will be described in detail. The following description is an example of an embodiment of the present invention, and the present invention is not limited thereto in any way.

[0021] In the present specification, the term "homogeneous" means that the catalyst is in the same state as the reaction system, and means, for example, that the catalyst dissolves in the solution in a reaction proceeding in the solution. In addition, the term "heterogeneous" means that the catalyst exists in a state different from that of the reaction system, and means, for example, that the catalyst exists as a solid in the solution in a reaction proceeding in the solution. The catalyst according to the present invention corresponds to a heterogeneous catalyst.

[0022] [Catalyst] The catalyst according to the present embodiment comprises an inorganic support and a mononuclear palladium complex supported on the inorganic support.

[0023] [Inorganic Support] The inorganic support in the present embodiment can be appropriately selected within a range where the mononuclear palladium complex can be supported. The inorganic support may be particles, or may have other forms, for example, an integrated structure having a specific shape such as monolithic silica or another sintered body. In addition, the inorganic support is preferably a porous body from the viewpoints of supporting a large amount of the mononuclear palladium complex and improving the contact property of the supported mononuclear palladium complex when used in a synthesis reaction.

[0024] When the inorganic support is granular, its particle size is preferably 0.1 μm or larger, more preferably 1 μm or larger, and even more preferably 10 μm or larger, from the viewpoint of achieving sufficient mechanical strength and improving solid-liquid separation properties. Furthermore, from the viewpoint of sufficiently improving the dispersibility of the catalyst in liquid, the particle size of the inorganic support is preferably 10,000 μm or smaller, more preferably 5,000 μm or smaller, and even more preferably 3,000 μm or smaller.

[0025] The volume-average particle diameter of an inorganic support can be determined, for example, by measuring the particle diameters of any 100 inorganic supporters (or catalysts) using an optical microscope and then determining the volume median diameter from their distribution. Furthermore, the volume-average particle diameter of an inorganic support can be adjusted, for example, by classifying the inorganic support or by using a mixture thereof.

[0026] The specific surface area of ​​the inorganic support is 0.1 m², from the viewpoint of supporting a sufficient amount of palladium mononuclear complex on the inorganic support. 2 It is preferable that it is 1m or more per gram. 2 It is more preferable that the amount is 3,000 m² or more. Furthermore, the specific surface area of ​​the inorganic support is 3,000 m² from the viewpoint of sufficiently exhibiting mechanical strength. 2 It is preferable that the amount be less than or equal to 2,000m 2 It is more preferable that the value be less than or equal to / g.

[0027] The specific surface area of ​​the inorganic support can be measured using known measurement techniques, such as the nitrogen gas adsorption method (BET method) which follows ISO 9277:2022.

[0028] The pore diameter of the inorganic support is preferably 1 Å or larger, more preferably 10 Å or larger, and even more preferably 15 Å or larger, from the viewpoint of sufficiently increasing the contactability of the palladium mononuclear complex during the synthesis reaction. Furthermore, the pore diameter of the inorganic support is preferably 10,000 Å or smaller, more preferably 5,000 Å or smaller, and even more preferably 2,000 Å or smaller, from the viewpoint of sufficiently exhibiting mechanical strength and supporting a sufficient amount of palladium mononuclear complex on the inorganic support.

[0029] The pore diameter of the inorganic carrier can be measured by known measurement techniques, such as the mercury intrusion method using ISO 15901-1:2016, and may be the most frequent diameter (modal pore diameter) obtained by said mercury intrusion method.

[0030] From the viewpoint of sufficiently increasing the contactability of the palladium mononuclear complex during the synthesis reaction, the pore volume of the inorganic support is preferably 0.01 mL / g or more, more preferably 0.1 mL / g or more, and even more preferably 0.3 mL / g or more. Furthermore, from the viewpoint of sufficiently exhibiting mechanical strength and supporting a sufficient amount of palladium mononuclear complex on the inorganic support, the pore volume of the inorganic support is preferably 1,000 mL / g or less, more preferably 100 mL / g or less, and even more preferably 10 mL / g or less.

[0031] The pore volume of the inorganic carrier can be measured by known measurement techniques, such as the mercury intrusion method using ISO 15901-1:2016, and can be determined by this mercury intrusion method assuming the pore shape is cylindrical.

[0032] The specific surface area, pore diameter, and pore volume of the inorganic support described above can be adjusted, respectively, by activation treatment, heat treatment, or particle size of the primary particles.

[0033] Examples of inorganic carriers include carriers consisting of at least one selected from the group consisting of activated carbon, silicon carbide, metal oxides, metal composite oxides, and metal salts of oxoacids.

[0034] Examples of metal oxides include alkaline earth metal oxides, alumina, silica, titania, iron oxide, cobalt oxide, yttrium oxide, zirconium oxide, niobium oxide, molybdenum oxide, tungsten oxide, bismuth oxide, lanthanum oxide, and cerium oxide.

[0035] Examples of metal composite oxides include silica-alumina, silica-titania, clay minerals, and zeolites.

[0036] Examples of metal salts of oxoacids include alkaline earth metal phosphates, zirconium phosphate, and lanthanum phosphate.

[0037] In this embodiment, the inorganic support is preferably activated carbon from the viewpoint of suppressing the outflow of palladium mononuclear complexes from the catalyst. Furthermore, from the viewpoint of being less expensive, the inorganic support is also preferably activated carbon.

[0038] Examples of activated carbon include plant-based activated carbon made from materials such as charcoal, coconut shell charcoal, palm kernel charcoal, or raw ash; coal-based activated carbon made from materials such as peat, lignite, brown coal, bituminous coal, or anthracite; petroleum-based activated carbon made from materials such as petroleum residue or oil carbon; and synthetic resin-based activated carbon made from materials such as polyvinylidene carbide.

[0039] In this embodiment, the activated carbon may be a commercially available product. Examples of such commercially available products include Shirasagi (registered trademark) C, Shirasagi M, Shirasagi P, Granular Shirasagi GX, SX, CX, XRC, KL, ANOX-1, ANOX-2, FAC-10 (manufactured by Osaka Gas Chemical Co., Ltd.), PCB (manufactured by Toyo Calgon Co., Ltd.), Yashikol (registered trademark, manufactured by Taihei Chemical Industry Co., Ltd.), Kuraraycol (registered trademark) GG, GC (manufactured by Kuraray Co., Ltd.), and activated carbon (powder) (manufactured by Kanto Chemical Co., Ltd.).

[0040] [Palladium mononuclear complex] In this embodiment, the palladium mononuclear complex comprises a palladium atom and a single palladium ligand coordinately bonded to the palladium atom. The term "palladium mononuclear complex" refers to a complex in which the core metal of the complex is a single palladium atom, and one or more ligands are bonded to that single palladium atom.

[0041] The valency of the palladium atom in the palladium mononuclear complex may be 0, 1, or 2, and is preferably 2 from the viewpoint of catalyst stability.

[0042] A palladium mononuclear complex may have at least one monolithic ligand, and may have two or more monolithic ligands.

[0043] <Single-sided ligand> A "single phosphorus ligand" refers to a ligand that has one phosphorus atom bonded to palladium. In this embodiment, the single phosphorus ligand has one phosphorus atom and an aromatic ring. The single phosphorus ligand has only one phosphorus atom that bonds to the palladium atom, but may also have further phosphorus atoms that do not bond to the palladium atom.

[0044] The monolithic ligand has at least one aromatic ring. This aromatic ring is readily adsorbed onto an inorganic support (especially activated carbon) and prevents the palladium mononuclear complex supported on the inorganic support from detaching from the inorganic support and leaching out of the catalyst. The aromatic ring is appropriately selected within a range that has sufficient adsorption to the inorganic support, and may be, for example, an aromatic hydrocarbon group having 6 to 12 carbon atoms, and may have substituents. Examples of substituents include halogen atoms, optionally substituted C1 to C6 alkyl halides, optionally substituted C1 to C6 alkyl groups, optionally substituted C2 to C6 alkoxy groups, alkoxycarbonyl groups, carboxyl groups, optionally substituted C1 to C6 dialkylamino groups, sulfo groups, and sulfonic acid bases.

[0045] The monophosphate ligand may further have groups other than the aromatic ring described above. For example, the monophosphate ligand may further have a non-aromatic ring bonded to the phosphorus atom. Examples of such non-aromatic rings include C1-C6 alkyl groups which may have substituents, and C1-C12 cycloalkyl groups which may have substituents. It is preferable for the monophosphate ligand to further have an alkyl group from the viewpoint of improving the solubility of the palladium mononuclear complex in organic solvents, and is suitable in the production of the complex described later. Furthermore, it is preferable for the monophosphate ligand to further have bulky substituents such as the above-mentioned cycloalkyl group and tert-butyl group, in addition to the viewpoint of improving solubility, from the viewpoint of improving coupling reactivity.

[0046] In a single phosphorus ligand, the maximum number of phosphorus atoms bonded to a palladium atom is three. From the viewpoint of ease of support on an inorganic carrier, at least one aromatic ring is required to bond to the phosphorus atom. Furthermore, from the viewpoint of controlling the reactivity with the phosphorus atom, it is desirable for two or more aromatic rings to bond to the phosphorus atom.

[0047] The single silyn ligand may have, in addition to or instead of the aromatic ring described above, further bonding substituents that are easily supported on an inorganic carrier. These bonding substituents can be appropriately determined depending on the type of inorganic carrier. The aforementioned aromatic ring is particularly relevant as a bonding substituent when the inorganic carrier is activated carbon.

[0048] Examples of single-unit ligands in this embodiment include the following specific examples.

[0049] [ka]

[0050] The palladium mononuclear complex in this embodiment may further have other ligands besides the monosodium ligand described above, to the extent that the effects of the present invention are obtained. Examples of such other ligands include anionic ligands such as halogen atoms, trifluoromethylsulfonyloxy groups, tosyloxy groups, mesyloxy groups, acetyloxy groups, and trifluoromethylacyloxy groups, as well as neutral ligands such as 1,5-cyclooctadiene, trans,trans-dibenzylideneacetone, and triphenylphosphine. Among these, the other ligand is preferably a chlorine atom, a bromine atom, or a mesyloxy group, from the viewpoint of the stable existence of the palladium mononuclear complex.

[0051] The palladium mononuclear complex in this embodiment can be obtained, for example, by synthesis using the monosodium ligand described above. Alternatively, the palladium mononuclear complex in this embodiment may be used as is if a commercially available product exists. Alternatively, the palladium mononuclear complex in this embodiment may be prepared by modifying a portion of a commercially available product to introduce or replace some substituents.

[0052] Examples of palladium mononuclear complexes in this embodiment include the following specific examples.

[0053] [ka]

[0054] In the catalyst of this embodiment, the amount of palladium mononuclear complex supported on the inorganic support can be appropriately determined within a range in which the effects of the present invention can be obtained. If the amount of palladium mononuclear complex supported is too small, the function of the catalyst when used in the synthesis reaction may be insufficient, and if the amount supported is too large, the amount of palladium mononuclear complex leaching from the inorganic support when used in the synthesis reaction may be large. From the viewpoint of fully exhibiting the function of the catalyst, the amount of palladium mononuclear complex supported on the inorganic support is preferably 10 ppm or more, more preferably 100 ppm or more, and even more preferably 300 ppm or more, in terms of palladium content per unit mass of catalyst. Furthermore, from the viewpoint of sufficiently suppressing the leaching of palladium mononuclear complex from the inorganic support, the amount of palladium supported on the inorganic support is preferably 250,000 ppm or less, more preferably 150,000 ppm or less, and even more preferably 100,000 ppm or less, in terms of palladium content per unit mass of catalyst.

[0055] The amount of palladium mononuclear complex supported on the inorganic support can be determined by known techniques capable of measuring the palladium content in the catalyst of this embodiment. For example, from the perspective of production control, this amount can be determined in the catalyst manufacturing process by subtracting the amount of unadsorbed complex from the amount of complex used. Alternatively, it can be determined from the catalyst itself by the palladium content in the catalyst ash. Furthermore, the palladium mononuclear complex supported on the inorganic support can be identified by extraction with an organic solvent and instrumental analysis of the extract (nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), and mass spectrometry (MS), etc.). Extraction with an organic solvent should be carried out at a temperature higher than the reaction temperature using the catalyst of this embodiment, for example, by extraction with toluene or xylene at reflux temperature.

[0056] Furthermore, the amount of palladium mononuclear complex supported in the inorganic support can be increased by immersing the existing catalyst according to this embodiment in a solution of palladium mononuclear complex, similar to the manufacturing method described later. Alternatively, the amount of supported material can be reduced by solvent extraction under conditions above the reaction temperature described above.

[0057] Furthermore, the catalyst of this embodiment may further contain other components besides the inorganic support and palladium mononuclear complex described above, to the extent that the effects of the present invention are obtained. Examples of such other components include binder resins that bind the inorganic support or catalyst particles together. The type and amount of such other components can be appropriately determined to the extent that both the effects of the present invention and the effects of the other components are obtained.

[0058] The catalyst of this embodiment is composed of an inorganic support on which a palladium mononuclear complex having a single phosphate ligand bonded to one or more aromatic rings is adsorbed. Because the palladium mononuclear complex has a single phosphate ligand with an aromatic ring, the aromatic ring is adsorbed to the inorganic support by van deswaal forces or surface charges. Adsorption is particularly strong when the inorganic support is activated carbon. This is thought to be because both the graphene structure of activated carbon and the aromatic ring of the palladium mononuclear complex are aromatic ring structures, and they interact with each other, resulting in strong adsorption. Therefore, even when the catalyst of this embodiment is used in a synthesis reaction, the palladium mononuclear complex does not detach from the inorganic support, and the catalyst of this embodiment can maintain a high loading rate of the palladium mononuclear complex. Thus, by using the catalyst of this embodiment as a palladium catalyst in a synthesis reaction, the synthesis reaction can proceed efficiently, and the contamination of the product by palladium atoms from the synthesis reaction can be prevented. Furthermore, since the catalyst of this embodiment can be recovered even after use in the synthesis reaction with the palladium mononuclear complex adsorbed onto the inorganic support, high reusability can be expected.

[0059] [Method for manufacturing catalysts] [Solid-liquid contact process] The catalyst of this embodiment can be manufactured by a method including a solid-liquid contact step in which an inorganic support is brought into solid-liquid contact with a solution of a palladium mononuclear complex. For example, the catalyst of this embodiment is manufactured by adding and dispersing an inorganic support in a solution of a palladium mononuclear complex. The solid-liquid contact step only needs to be a step in which the palladium mononuclear complex is in sufficient contact with the inorganic support, and in addition to the above step of dispersion in a solution, it may also be a step in which the solution of the palladium mononuclear complex is circulated and continuously supplied to a fixed bed of inorganic support.

[0060] The state of the palladium mononuclear complex during catalyst production is such that it can be adsorbed and supported on an inorganic support, and from this viewpoint, it is preferable that it be dissolved in the solvent for preparation. The solvent used in this case is not particularly limited, but from the viewpoint of having sufficiently high solubility for the palladium mononuclear complex and not substantially coordinating with the central metal palladium, non-aromatic hydrocarbon solvents such as hexane, heptane, octane, and cyclohexane, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and mesitylene, and aliphatic alcoholic solvents such as methanol and ethanol are preferred. In particular, from the viewpoint of high solubility for the palladium mononuclear complex, toluene, ethanol, and methanol are preferred. Furthermore, if the palladium mononuclear complex is difficult to dissolve in the solvent for preparation, two or more solvents may be mixed and used as needed.

[0061] In the solid-liquid contact step, the dispersion obtained by adding the inorganic support to the solution of the palladium mononuclear complex with the inorganic support added may be stirred or left to stand. The temperature of the solution in the solid-liquid contact step is not particularly limited, and the solution may be heated, or the solid-liquid contact step may be carried out at room temperature. The preparation completion time can be appropriately set depending on the type or amount of inorganic support and palladium mononuclear complex. For example, if the inorganic support is activated carbon, the conditions (concentration of the palladium mononuclear complex in the solution, temperature of the solution after adding the inorganic support, stirring speed of the solution, and stirring and standing time, etc.) should be set so that the impregnation is completed in 1 hour to 7 days in practice.

[0062] [Other processes] The catalyst manufacturing method of this embodiment may further include other steps besides the solid-liquid contact step described above, to the extent that the effects of the present invention are obtained. Examples of such other steps include a solid-liquid separation step, a washing step, and a drying step.

[0063] <Solid-liquid separation process> The solid-liquid separation step is a step of separating the catalyst prepared in the solid-liquid contact step from the dispersion. The solid-liquid separation step may be carried out during or after the solid-liquid contact step by adjusting the temperature of the dispersion to evaporate the solvent, by distillation at atmospheric pressure or reduced pressure to remove the solvent from the dispersion, or by filtering the catalyst from the dispersion by filtration such as pressure filtration or vacuum filtration. Such a solid-liquid separation step is preferred from the viewpoint of increasing the amount of palladium mononuclear complex adsorbed onto the inorganic support and from the viewpoint of facilitating handling in subsequent steps such as the washing step described below.

[0064] <Washing process> The catalyst separated in the solid-liquid separation step may be washed with a washing solvent. Including a further washing step to wash the inorganic support after the solid-liquid contact step is preferable from the viewpoint of sufficiently removing palladium mononuclear complexes that were not adsorbed onto the inorganic support from the obtained catalyst. The washing solvent can be appropriately selected within a range that allows excess palladium mononuclear complexes to be leached out of the catalyst. Examples of such washing solvents include organic solvents or filtrates when the solid-liquid separation step is filtration. From the viewpoint of enhancing the washing effect, it is preferable that the washing solvent is the same as the solvent used during preparation.

[0065] <Drying process> The catalyst obtained by the above manufacturing method may contain a solvent such as a washing solvent, but this solvent may be removed from the catalyst by a drying step. Such a drying step is preferable from the viewpoint of improving the shelf life of the catalyst. The drying step is preferably carried out by vacuum drying from the viewpoint of suppressing the effect of the drying temperature on the catalyst and from the viewpoint of storing the catalyst. The degree of vacuum during vacuum drying is not particularly limited, but is preferably about 20 torr (2.7 kPa) or less. Heating may be carried out as necessary during the drying step, and the heating temperature is preferably 40°C or less from the viewpoint of the shelf life of the catalyst.

[0066] In the catalyst manufacturing method of this embodiment, chemical modification is not required for either the monosodium ligand that coordinates to the palladium mononuclear complex or the inorganic support that serves as the carrier, in order to support the palladium mononuclear complex on the inorganic support. Therefore, the catalyst manufacturing method of this embodiment is advantageous in that it can be synthesized more easily than conventional solid-supported palladium catalysts that utilize chemical modification.

[0067] [Method for producing compounds] [Synthesis process] The catalyst of this embodiment can be applied to various organic synthesis reactions that use a palladium complex as a catalyst. Examples of such organic synthesis reactions include reactions that synthesize biaryl compounds such as biphenyls using a palladium catalyst. Examples of such synthesis reactions include the Suzuki-Miyaura coupling reaction and the Migita-Kosugi-Stillcross coupling reaction. Thus, the method for producing a compound using the catalyst of this embodiment may include a step of synthesizing the compound by a Migita-Kosugi-Stillcross coupling reaction in the presence of the catalyst of this embodiment as the compound synthesis step. The method for producing a compound of this embodiment can be carried out under conventionally known conditions, except for the use of the catalyst of this embodiment as a heterogeneous catalyst, and can be applied to the final stage of synthesis reactions of compounds with complex structures, including the synthesis of natural products.

[0068] The solvent used in the Migita-Kosugi-Stillcross coupling reaction is preferably a solvent that does not interfere with the desired reaction, is substantially inert in the reaction, and has sufficiently high solubility for the compounds used in the reaction. Specifically, the solvent is preferably at least one selected from the group consisting of benzene, chlorobenzene, toluene, xylene, mesitylene, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, methyl-tert-butyl ether, ethyl acetate, acetone, dichloromethane, chloroform, methanol, ethanol, and acetonitrile.

[0069] The reaction temperature in the Migita-Kosugi-Stillcross coupling reaction can be appropriately determined depending on the starting compound used. From the viewpoint of achieving a sufficient reaction rate and suppressing the effect of temperature on the catalyst, the reaction temperature is preferably 10°C to 200°C, more preferably 20°C to 180°C, and even more preferably 40°C to 150°C.

[0070] The reaction time in the Migita-Kosugi-Stillcross coupling reaction can be appropriately determined depending on the starting compound used, or based on the detection results of the starting compound or product during the reaction. From the viewpoint of achieving both sufficient progress of the main reaction and suppression of side reactions, the reaction time is preferably 1 minute to 20 hours, more preferably 3 minutes to 15 hours, and even more preferably 5 minutes to 12 hours.

[0071] Furthermore, the compound manufacturing method of this embodiment is advantageous for the production of functional organic compounds in which palladium contamination is substantially unacceptable. A "functional organic compound" refers to an organic compound that exhibits a specific function, and in which the expression of that function may be suppressed or inhibited by palladium contamination. In the compound manufacturing method of this embodiment, since the catalyst of this embodiment is used, it can be used in various synthesis reactions in which heterogeneous palladium catalysts are applicable, and the outflow of palladium into the liquid phase containing the product is sufficiently suppressed. Therefore, palladium contamination of the product is prevented, or the purification process to remove palladium from the product is simplified. Accordingly, the compound manufacturing method of this embodiment is suitable, for example, for the synthesis of functional organic compounds having a π-conjugated structure (π-conjugated functional organic compounds) in the presence of the catalyst of this embodiment. Examples of such functional compounds include pharmaceutical compounds contained as active ingredients in antihypertensive drugs, liquid crystal compounds contained in TN-type liquid crystal layers, and electron-transporting compounds contained in electron transport layers in organic EL elements. Thus, the compound production method of this embodiment, which includes a step of synthesizing a functional organic compound having a π-conjugated structure such as a biaryl structure and a thiophene structure in the presence of a catalyst as a compound synthesis step, is preferable from the viewpoint of omitting or simplifying the purification step to remove palladium in the production of organic compounds in which palladium contamination is substantially unacceptable.

[0072] The synthesis step described above in this embodiment may also be a continuous flow reaction step. Such a synthesis step can be carried out, for example, by packing the catalyst of this embodiment into a column, maintaining the column at the above reaction temperature, and supplying a reaction solution such as a substrate mixed with a solvent and a base to a fixed bed of catalyst constructed in the column using a metering pump, and circulating the reaction solution to the fixed bed as needed. Such a synthesis step using a continuous flow reaction is advantageous from the viewpoint of being able to produce the target compound without requiring the operation of separating the catalyst from the reaction solution containing the product, thus eliminating the need for catalyst separation.

[0073] Furthermore, the present invention also exhibits excellent performance in the synthesis of polymers using palladium as a catalyst. Here, "polymer" refers to a polymer with a weight-average molecular weight of 8,000 or more, preferably 10,000 or more, calculated using polystyrene equivalent values ​​in gel permeation chromatography (GPC).

[0074] [Other processes] The method for producing the compound of this embodiment may further include other steps besides the synthesis step described above, to the extent that the effects of the present invention are obtained. Examples of such other steps include a catalyst separation step and a catalyst washing step.

[0075] <Catalyst separation process> The catalyst separation step is a step performed after the synthesis step to separate the catalyst of this embodiment from the reaction solution of the target product. The catalyst separation step can be carried out by simple methods such as decantation or filtration. The catalyst of this embodiment separated in the catalyst separation step can be reused as is in the next reaction. In this case, the solvent may be removed from the separated catalyst by a drying step or the like, or the catalyst may be reused with the solvent still present.

[0076] <Catalytic Cleaning Process> The catalyst washing step is a step in which the catalyst used in the synthesis step is washed. The catalyst washing step can be carried out, for example, by washing the catalyst extracted in the catalyst separation step with a solvent. The solvent used for washing the catalyst is preferably a solvent that has high solubility for the product and has a strong interaction with the inorganic support, from the viewpoint of extracting the product remaining in the inorganic support. For example, when the inorganic support is activated carbon, the washing solvent preferably contains a solvent having an aromatic ring that has a strong π-π interaction with the graphene structure of the activated carbon, and is particularly preferably an aromatic hydrocarbon solvent. Specific examples of such solvents include benzene, toluene, xylene, mesitylene, ethylbenzene, cumene, 1,2,3,4-tetrahydronaphthalene, indan, and phenylcyclohexane. If the solubility of the product is low in these solvents, it is preferable to use a mixed solvent, which is a solvent with higher solubility for the product, as the washing solvent, from the viewpoint of enhancing the washing effect.

[0077] When the catalyst of this embodiment is used in the method for producing the above compound, the palladium mononuclear complex does not substantially leak from the catalyst (inorganic support). This characteristic of the catalyst of this embodiment can be demonstrated, for example, by the fact that the palladium content in the solvent is zero or trace when dispersed in a solvent under conditions equivalent to the synthesis conditions in the method for producing the compound. More specifically, when a dispersion of toluene containing 10% by mass of the catalyst of this embodiment is refluxed under a nitrogen atmosphere for 1 hour, the dispersion is filtered to remove the catalyst, and the filtrate is pretreated by wet decomposition or microwave acid decomposition, the palladium content when the obtained sample is measured by inductively coupled plasma atomic emission spectrometry (ICP) is 10 ppm or less or below the limit of quantification.

[0078] As described above, one embodiment of the present invention relates to a catalyst containing an inorganic support on which a palladium mononuclear complex is adsorbed. Generally, the amount of palladium catalyst used in synthesis reactions is small. However, since palladium catalysts are expensive, even a small amount accounts for a relatively large proportion of the raw material cost. The catalyst of this embodiment can be reused when used in synthesis reactions that require a palladium catalyst, which is advantageous in reducing raw material costs. Furthermore, in the synthesis reaction, it can be easily separated by solid-liquid separation, and palladium does not substantially leak from the catalyst into the solvent. Therefore, by using the catalyst of this embodiment in the above synthesis reaction, the purification step for palladium removal in the synthesis reaction can be simplified or reduced, which is advantageous in reducing production costs.

[0079] According to the embodiments of the present invention described above, the heterogeneous palladium catalyst of this embodiment can be prepared by mixing an inorganic support and a homogeneous palladium complex in a solvent, drying, and then washing, without requiring any modification of the structure of the homogeneous palladium complex for preparing the heterogeneous palladium catalyst. Therefore, the catalytic function of the palladium mononuclear complex can be utilized to the fullest extent. Furthermore, since the palladium mononuclear complex is sufficiently firmly supported on the inorganic support, the outflow of supported palladium is sufficiently suppressed even after use in the synthesis reaction of organic compounds, and the process of removing the outflowed palladium can be omitted or simplified. The present invention, which provides such effects, is expected to contribute to achieving, for example, Goal 12 of the United Nations Sustainable Development Goals (SDGs), "Responsible Consumption and Production."

[0080] The present invention is not limited to the embodiments described above, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention. [Examples]

[0081] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist of the invention. In the examples, "parts" or "%" means by mass unless otherwise specified.

[0082] The yield was calculated by sampling the filtrate and performing high-performance chromatographic (HPLC) measurements, then comparing the obtained peak area with the peak area obtained from HPLC measurements using commercially available 2,2'-bithiophene as a standard.

[0083] The weight-average molecular weight of the polymer was measured by sampling the reaction solution and determining its polystyrene equivalent value using gel permeation chromatography (GPC).

[0084] The palladium mononuclear complex used was bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II). This palladium mononuclear complex was prepared by purchasing reagents from Tokyo Chemical Industry Co., Ltd.

[0085] [Example 1: Catalyst Manufacturing Example] Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (44.4 mg, 0.063 mmol), toluene (39 mL), ethanol (2 mL), and ANOX-2 (activated carbon, Osaka Gas Chemical Co., Ltd., 5.02 g) were added to a 300 mL beaker, and the resulting suspension was allowed to stand for 4 days, after which the solvent was evaporated from the suspension.

[0086] Toluene (30 mL) and ethanol (1.5 mL) were added to the beaker containing the obtained solid component, and after stirring for 1 minute, the resulting dispersion was filtered by suction. The solid obtained by this solid-liquid separation was transferred to a 300 mL beaker, and then toluene (30 mL) and ethanol (1.5 mL) were added to the beaker again, and after stirring for 1 minute, the resulting dispersion was filtered by suction.

[0087] The solid components recovered by filtration were dried under reduced pressure at 40°C for 6 hours to obtain 5.78 g of supported catalyst A. The recovered filtrate was concentrated under reduced pressure to recover the solid. Since the recovered solid amounted to 12.6 mg, the adsorption rate of the palladium complex to activated carbon was calculated to be 71.6%.

[0088] [Example 2: Synthesis of a compound using a catalyst] 2-bromothiophene (0.083 g, 1.0 mmol), tributyl(2-thienyl)tin (0.185 g, 1.0 mmol), and supported complex A obtained in Example 1 (0.64 g, 0.01 mmol) were added to a 60 mL test tube, to which toluene (5 mL) and N-methylpyrrolidone (0.5 mL) were added. The atmosphere in the test tube was replaced with nitrogen, and the mixture was heated to 100 °C and stirred. The reaction was monitored by HPLC, and the reaction continued until the area percentage of the target product reached 99.6%, which took 18 hours. The reaction mixture was filtered by Celite® suction filtration to obtain 29.2 g of filtrate. The filtrate was measured by high-performance chromatography (HPLC), and the target 4-methylbiphenyl was obtained in 46% yield.

[0089] Furthermore, the filtrate was weighed and subjected to wet decomposition with acid. After recovery and volume adjustment, palladium was quantitatively measured using an ICP emission spectrometer (Agilent 5800), and the result was below the detection limit of 1 ppm. From this, it was estimated that the filtrate contained less than 0.0292 mg of palladium. Since 0.532 mg of palladium was used in the reaction, the palladium leakage rate was calculated to be less than 5.5%.

[0090] [Example 3: Synthesis of polymers using a supported catalyst] 4,6-dibromo-3-fluorothieno[3,4-b]thiophene-2-carboxylic acid 2-ethylhexyl (0.044 g, 0.09 mmol), 4,8-bis[(2-ethylhexyl)oxy]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene (0.077 g, 0.10 mmol), and supported catalyst A obtained in Example 1 (0.44 g, 0.002 mmol) were added to a 60 mL test tube, and toluene (5 mL) and N,N-dimethylformamide (0.5 mL) were added. The atmosphere in the test tube was replaced with nitrogen, and the mixture was heated at 100 °C and stirred for 4 hours. GPC analysis confirmed the formation of a polymer with a weight-average molecular weight of 27,000. The reaction solution was filtered by Celite® suction filtration, and the solvent was removed from the filtrate by reduced pressure concentration and vacuum drying to obtain 0.05 g of dry material.

[0091] Furthermore, the obtained dry material was wet-decomposed with acid. After recovery and volume adjustment, palladium was quantitatively measured using an ICP emission spectrometer (Agilent 5800), which yielded 850 ppm (palladium leakage rate 48.9%).

[0092] [Comparative example: Synthesis of polymers using a homogeneous catalyst] 4,6-dibromo-3-fluorothieno[3,4-b]thiophene-2-carboxylic acid 2-ethylhexyl (0.044 g, 0.09 mmol), 4,8-bis[(2-ethylhexyl)oxy]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene (0.077 g, 0.1 mmol), and bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (1.3 mg, 0.002 mmol) obtained in Example 1 were added to a 60 mL test tube, and toluene (5 mL) and N,N-dimethylformamide (0.5 mL) were added. The atmosphere in the test tube was replaced with nitrogen, and the mixture was heated at 100 °C and stirred for 4 hours. GPC analysis confirmed the formation of a polymer with a weight-average molecular weight of 16,000. The reaction solution was subjected to Celite® suction filtration, and the solvent was removed from the filtrate by reduced pressure concentration and vacuum drying to obtain 0.08 g of dry material.

[0093] Furthermore, the obtained dry material was wet-decomposed with acid. After recovery and volume adjustment, palladium was quantitatively measured using an ICP emission spectrometer (Agilent 5800), which yielded 1700 ppm (palladium leakage rate 97.8%).

[0094] When a homogeneous catalyst is used in the reaction, 100% of the palladium complex remains in the reaction solution. However, the results of Example 2 show that even when a supported catalyst is used in the reaction, almost no palladium leaks into the reaction solution. This indicates that most of the palladium complex is supported on the activated carbon.

[0095] Furthermore, the results from Example 3 and the comparative example show that using a supported catalyst in the reaction can suppress the contamination of the polymer with palladium.

[0096] As described above, the catalyst of the present invention can be used in a reaction to allow the reaction to proceed while suppressing the contamination of the product with palladium complexes. [Industrial applicability]

[0097] This invention can be used in organic synthesis reactions that proceed in the presence of heterogeneous palladium catalysts.

Claims

1. It comprises an inorganic support and a palladium mononuclear complex supported on the inorganic support, The palladium mononuclear complex comprises a palladium atom and a monosodium ligand coordinately bonded to the palladium atom. The catalyst is characterized in that the single phosphorus ligand has one phosphorus atom and an aromatic ring, the phosphorus atom being coordinately bonded to the palladium atom.

2. The catalyst according to claim 1, wherein the catalyst is for the synthesis of polymer compounds.

3. The catalyst according to claim 1, wherein the inorganic support is activated carbon.

4. A method for producing a compound, comprising the step of synthesizing a π-conjugated functional organic compound in the presence of a catalyst according to any one of claims 1 to 3.

5. The method for producing a compound according to claim 4, wherein the synthesis step is a step of synthesizing the compound by a Migita-Kosugi-Stillcross coupling reaction in the presence of the catalyst.

6. A method for producing the catalyst described in any one of claims 1 to 3, A method for producing a catalyst, comprising the step of bringing the inorganic support into solid-liquid contact with a solution of the palladium mononuclear complex.

7. The method for producing a catalyst according to claim 6, wherein the single siline ligand further comprises an alkyl group.

8. The method for producing a catalyst according to claim 6, further comprising the step of washing the inorganic support after the step of bringing it into solid-liquid contact.

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