Method for producing chemical compound using intermetallic compound-carried zirconium carbide catalyst

Abstract

To provide a method for producing a chemical compound using intermetallic compound-carried zirconium carbide having high activity as a catalyst capable of obtaining an aimed chemical compound in a short time with high yield, and capable of obtaining the chemical compound in a short time with high yield even if using the catalyst repeatedly.SOLUTION: A method for producing a chemical compound includes a reaction process (A) of using an intermetallic compound-carried zirconium carbide carried with particles of an intermetallic compound of palladium and zirconium on zirconium carbide having a nanoporous structure as a catalyst where the reaction process (A) is performed under an oxygen atmosphere.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a compound using an intermetallic compound-supported zirconium carbide catalyst. [Background technology]

[0002] Organic synthesis reactions catalyzed by metal complexes have been known for a long time, and reactions that form carbon-carbon bonds (CC bonds), such as Suzuki coupling, can be said to be essential reactions for synthesizing the skeletons of organic compounds. The organoboron compounds required for the Suzuki coupling reaction are relatively non-toxic and, unlike other organometallic compounds, are stable in water. Furthermore, the Suzuki coupling reaction proceeds under mild conditions, making it highly valuable industrially.

[0003] Homogeneous palladium catalysts have been widely used in Suzuki coupling reactions. Heterogeneous palladium catalysts, on the other hand, do not require ligands and are recoverable, offering cost and environmental advantages. Metal-supported catalysts, in which palladium is supported on a support (carbon or metal oxide), are a typical heterogeneous catalyst. However, due to the weak mechanical and electronic interactions between the support and palladium, condensation and desorption of palladium atoms are likely to occur, and it is difficult to achieve electron-rich palladium.

[0004] Patent Document 1 solves the above problems by reporting that zirconium carbide supported on an intermetallic compound of zirconium and palladium (ZrPd3) functions as a solid catalyst with high activity and stability for Suzuki coupling reactions, and that by calcining a mixture of zirconium polymer and palladium acetate at high temperature, it is possible to obtain zirconium carbide supported on an intermetallic compound with high palladium dispersion and electron-rich, stable palladium sites. The compound disclosed in Patent Document 1 functions as a solid catalyst with high activity and stability. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2021 / 220800 Summary of the Invention [Problem to be solved by the invention]

[0006] As described above, the intermetallic compound-supported zirconium carbide disclosed in Patent Document 1 has palladium dispersed on the zirconium carbide, and is electron-rich and stable, so it functions as a solid catalyst with high activity and stability. When considering the function of a catalyst, it is first necessary that it has high activity and can produce the target compound in high yield in a short time. Furthermore, it is required that the catalytic activity be maintained even when a used catalyst is reused, that is, the target compound can be produced in high yield in a short time even when reused. The present inventors noticed that when the reaction is carried out under a nitrogen atmosphere, the reaction proceeds but the yield of the target compound decreases, and when a used catalyst is repeatedly used, the reaction time required to produce the target compound in high yield becomes longer from the second cycle onwards, and the catalytic activity is significantly reduced.

[0007] Therefore, an object of the present invention is to provide a method for producing a compound that uses a highly active intermetallic compound-supported zirconium carbide as a catalyst, which can produce a target compound in high yield in a short period of time, and which can also produce a compound in high yield in a short period of time even when the catalyst is used repeatedly. [Means for solving the problem]

[0008] Generally, in coupling reactions using metal catalysts, the catalyst is deteriorated due to oxidation, and therefore an inert gas atmosphere is selected as the reaction atmosphere. However, after extensive research, the present inventors have found that the above-mentioned problems can be solved by carrying out the reaction in an oxygen atmosphere in the reaction step using the above-mentioned intermetallic compound-supported zirconium carbide as a catalyst, and have thus completed the present invention. That is, the present invention provides the following.

[0009] [1] A method for producing a compound, comprising a reaction step (A) using an intermetallic compound-supported zirconium carbide catalyst, in which particles of an intermetallic compound of palladium and zirconium are supported on zirconium carbide having a nanoporous structure, wherein the reaction step (A) is carried out in an oxygen atmosphere. [2] The production method according to the above item [1], wherein the reaction step (A) is a reaction represented by formula (1). [ka] [In formula (1), Ar 1 and Ar 2 each independently represents a substituted or unsubstituted aromatic hydrocarbon group or heteroaromatic hydrocarbon group, X represents at least one selected from the group consisting of halogen, mesyl group, tosyl group, perfluoroalkylsulfonyl group, diazonio group, and triflyl group, R 1 and R 2 are each independently a hydroxyl group, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms, or a phenoxy group which may have an alkyl group having 1 to 6 carbon atoms, and R 1 and R 2 may be linked to each other to form a ring as an ethylenedioxy group, a 2,3-dimethylbutane-2,3-dioxy group, a 2,2-dimethylpropane-1,3-dioxy group, a 3,4-diethylhexane-3,4-dioxy group, a biscyclohexyldioxy group, a pinanedioxy group, or a 1,2-phenylenedioxy group.] [3] The method according to the above item [1] or [2], wherein the oxygen atmosphere contains 1% by volume or more and 25% by volume or less of oxygen. [4] The method according to any one of the above items [1] to [3], wherein in the reaction step (A), an inorganic additive is present in an amount of 1 to 200 times by mass relative to the catalyst. [5] The method according to any one of the above items [1] to [4], wherein the reaction step (A) is carried out in the presence of a solvent. [6] The method according to item [5], wherein the solvent is water. [7] The method according to the above item [6], wherein the water content of the total solvent is 1 mass% or more. [8] The method according to any one of the above items [1] to [7], wherein the reaction step (A) is carried out in the presence of a base. [9] The base is added to water at a concentration of 0.01 mol / m 3 More than 12mol / m 3 The manufacturing method according to the above item [8], including the following:

[10] The method according to the above item [8] or [9], wherein the base comprises an alkali metal salt or an alkaline earth metal salt having a pKa of 1 or more and 20 or less of a conjugate acid. [Effects of the Invention]

[0010] According to the present invention, there is provided a method for producing a compound using a highly active intermetallic compound-supported zirconium carbide as a catalyst, which can produce a target compound in high yield in a short period of time, and can also produce a compound in high yield in a short period of time even when the catalyst is used repeatedly. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an embodiment of the present invention (hereinafter sometimes referred to as the present embodiment) will be described in detail, but the following description is an example of an embodiment, and the present invention is not limited to these in any way.

[0012] This embodiment relates to a method for producing a compound, which includes a reaction step using an intermetallic compound-supported zirconium carbide catalyst (hereinafter sometimes abbreviated as "intermetallic compound-supported ZrC catalyst"), in which particles of an intermetallic compound of palladium and zirconium are supported on zirconium carbide having a nanoporous structure. More specifically, the method is characterized in that the reaction step (A) using the intermetallic compound-supported zirconium carbide catalyst is carried out in an oxygen atmosphere. Even when a used catalyst is reused as the intermetallic compound-supported ZrC catalyst in the reaction step (A), the reaction step (A) is characterized by being carried out in an oxygen atmosphere.

[0013] <Intermetallic Compound Supported ZrC Catalyst> The intermetallic compound-supported ZrC catalyst used in this embodiment is a compound in which particles of an intermetallic compound of palladium and zirconium are supported on zirconium carbide having a nanoporous structure. The contents of WO 2021 / 220800 are incorporated herein by reference.

[0014] The above-mentioned intermetallic compound-supported ZrC catalyst is mainly used in Suzuki coupling reactions, but can also be used in other reactions, such as the hydrogenation of alkynes such as acetylene, and the hydrogenation of nitrobenzene. The above catalyst has the following advantages: 1) ZrPd3 is dispersed on zirconium carbide, which has a large surface area, and therefore has high activity. 2) Palladium forms an intermetallic compound with zirconium, but since zirconium has a lower electronegativity than palladium, the palladium in the intermetallic compound is in an electron-rich state and has high activity. 3) Since a large amount of energy is required for the aggregation and desorption of palladium in the intermetallic compound, this catalyst has high stability.

[0015] The above-mentioned intermetallic compound-supported ZrC catalyst has high activity in, for example, Suzuki coupling, but depending on the target compound, optimization of reaction conditions, such as selecting a solvent with high solubility for the raw materials, may be required to shorten the reaction time and obtain the product in high yield. Even in such cases, it is desirable for the catalyst to exhibit high activity and obtain the target compound in high yield in a short time. In general, in catalytic reactions using heterogeneous catalysts, catalytic activity may decrease due to changes in catalytic active sites during the reaction. When reusing a catalyst that has been used once, even if the catalytic active sites decrease, it is desirable to carry out the reaction under conditions that allow the reaction to proceed efficiently in order to obtain the target compound in high yield in a short period of time.

[0016] [Reaction step (A)] The reaction step (A) corresponds to a step of producing a compound using the above-mentioned intermetallic compound-supported ZrC catalyst as a catalyst. The catalyst used here may be an unused intermetallic compound-supported ZrC catalyst or a recovered catalyst that has been used in the reaction step and then recovered. The reaction in the reaction step (A) is not limited in any way as long as it uses the above-mentioned intermetallic compound-supported ZrC catalyst, and examples thereof include the Suzuki coupling reaction, the hydrogenation reaction of alkynes such as acetylene, and the hydrogenation reaction of nitrobenzene. The Suzuki coupling reaction is represented by the following formula (1): [ka] [In formula (1), Ar 1 and Ar 2 each independently represents a substituted or unsubstituted aromatic hydrocarbon group or heteroaromatic hydrocarbon group, X represents at least one selected from the group consisting of halogen, mesyl group, tosyl group, perfluoroalkylsulfonyl group, diazonio group, and triflyl group, R 1 and R 2 are each independently a hydroxyl group, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms, or a phenoxy group which may have an alkyl group having 1 to 6 carbon atoms, and R1 and R 2 may be linked to each other to form a ring as an ethylenedioxy group, a 2,3-dimethylbutane-2,3-dioxy group, a 2,2-dimethylpropane-1,3-dioxy group, a 3,4-diethylhexane-3,4-dioxy group, a biscyclohexyldioxy group, a pinanedioxy group, or a 1,2-phenylenedioxy group.]

[0017] In the above formula (1), Ar 1 and Ar 2 each independently represents a substituted or unsubstituted aromatic hydrocarbon group or heteroaromatic hydrocarbon group. From the viewpoint of the balance between solubility and durability, the aromatic hydrocarbon group or heteroaromatic hydrocarbon group preferably has 4 or more carbon atoms, more preferably 5 or more carbon atoms, and preferably 60 or less, more preferably 50 or less, even more preferably 40 or less, and most preferably 30 or less carbon atoms. The aromatic hydrocarbon group having 6 to 60 carbon atoms and the heteroaromatic hydrocarbon group having 4 to 60 carbon atoms may exist as a single ring or a condensed ring, or may be a group formed by bonding or condensing one ring to another type of aromatic hydrocarbon group or heteroaromatic hydrocarbon group.

[0018] Examples of these include a phenyl group, a naphthyl group, anthracenyl group, a benzanthracenyl group, a phenanthrenyl group, a benzophenanthrenyl group, a pyrenyl group, a chrysenyl group, a fluoranthenyl group, a perylenyl group, a benzopyrenyl group, a benzofluoranthenyl group, a naphthacenyl group, a pentacenyl group, a biphenyl group, a terphenyl group, a fluorenyl group, a spirobifluorenyl group, a dihydrophenanthrenyl group, a dihydropyrenyl group, a tetrahydropyrenyl group, an indenofluorenyl group, a furyl group, a benzofuryl group, an isobenzofuryl group, a dibenzofuranyl group, a thiophene group, a benzothiophenyl group, a dibenzothiophenyl group, a pyrrolyl group, an indolyl group, an isoindolyl group, a carbazolyl group, a benzocarbazolyl group, an indolocarbazolyl group, an indenocarbazolyl group, a pyridyl group, a cinnolyl group, an isocinnolyl group, an acridinyl group, a furyl ... a indolocarbazolyl group, an indenocarbazolyl group, a pyridyl group, a cinno A phenanthridinyl group, a phenothiazinyl group, a phenoxazinyl group, a pyrazolyl group, an indazolyl group, an imidazolyl group, a benzimidazolyl group, a naphthimidazolyl group, a phenanthroimidazolyl group, a pyridineimidazolyl group, an oxazolyl group, a benzoxazolyl group, a naphthoxazolyl group, a thiazolyl group, a benzothiazolyl group, a pyrimidyl group, a benzopyrimidyl group, a pyridazinyl group, a quinoxalinyl group, a diazaanthrin group, Examples include a phenyl group, a diazapyrenyl group, a pyrazinyl group, a phenoxazinyl group, a phenothiazinyl group, a naphthyridinyl group, an azacarbazolyl group, a benzocarbonyl group, a phenanthrenyl group, a triazolyl group, a benzotriazolyl group, an oxadiazolyl group, a thiadiazolyl group, a triazinyl group, a 2,6-diphenyl-1,3,5-triazin-4-yl group, a tetrazolyl group, a purinyl group, and a benzothiadiazolyl group.

[0019] These aromatic hydrocarbon groups or heteroaromatic hydrocarbon groups may further have a substituent. The substituent is not particularly limited as long as it does not adversely affect the reaction of formula (1), and examples thereof include D, F, Cl, Br, I, -N(R"), -CN, -NO, -Si(R"), -B(OR"), -C(=O)R", -P(=O)(R"), -S(=O)R", -OSOR", a linear or branched alkyl group having 1 to 30 carbon atoms, a cyclic alkyl group having 3 to 30 carbon atoms, a linear or branched alkoxy group having 1 to 30 carbon atoms, a cyclic alkoxy group having 2 to 30 carbon atoms, a linear or branched alkylthio group having 1 to 30 carbon atoms, a cyclic alkylthio group having 2 to 30 carbon atoms, a cyclic alkylthio group having 2 or more ... The R" is selected from a linear or branched alkenyl group having 3 to 30 carbon atoms, a cyclic alkenyl group having 3 to 30 carbon atoms, a linear or branched alkynyl group having 2 to 30 carbon atoms, a cyclic alkynyl group having 3 to 30 carbon atoms, an aromatic group having 5 to 60 carbon atoms, a heteroaromatic group having 1 to 60 carbon atoms, an aryloxy group having 5 to 40 carbon atoms, an arylthio group having 5 to 40 carbon atoms, an aralkyl group having 5 to 60 carbon atoms, a heteroaralkyl group having 2 to 60 carbon atoms, a diarylamino group having 10 to 40 carbon atoms, an arylheteroarylamino group having 10 to 40 carbon atoms, or a diheteroarylamino group having 10 to 40 carbon atoms. When multiple R"s are present, they may be the same or different. Each R" is independently selected from a hydrogen atom, D, F, -CN, an aliphatic hydrocarbon group having 1 to 20 carbon atoms, an aromatic group having 5 to 20 carbon atoms, or a heteroaromatic group having 1 to 20 carbon atoms. Two or more adjacent R"s may be bonded to each other to form an aliphatic, aromatic, or heteroaromatic monocyclic or fused ring. When there are multiple R", they may be the same or different. There are no particular limitations on these substituents as long as they do not adversely affect the reaction.

[0020] In the above formula (1), X represents at least one selected from the group consisting of halogen, mesyl group, tosyl group, perfluoroalkylsulfonyl group, diazonio group, and triflyl group. Examples of halogen atoms include chlorine atom, bromine atom, and iodine atom.

[0021] Ar 1 Suitable halogenated aryls represented by -X include halogenated benzenes, halogenated naphthalenes, etc. 1 and X are as described above. Among the above, X is preferably a bromine atom, an iodine atom, or a triflyl group from the viewpoints of reactivity and availability. For example, the aryl halide can be at least one selected from the group consisting of those typically used in Suzuki coupling reactions, such as iodobenzene, bromobenzene, 4-iodotoluene, 4-bromotoluene, 1-iodonaphthalene, 1-bromonaphthalene, 2-iodonaphthalene, 2-bromonaphthalene, 1-bromo-4-iodobenzene, p-tolyltrifluoromethanesulfonate, 4-iodophenyltrifluoromethanesulfonate, 4-bromophenyltrifluoromethanesulfonate, and 3-chlorophenyltrifluoromethanesulfonate.

[0022] In the above formula (1), R 1 and R 2 are each independently a hydroxyl group, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms, or a phenoxy group which may have an alkyl group having 1 to 6 carbon atoms, and R 1 and R 2 may be linked to each other to form a ring as an ethylenedioxy group, a 2,3-dimethylbutane-2,3-dioxy group, a 2,2-dimethylpropane-1,3-dioxy group, a 3,4-diethylhexane-3,4-dioxy group, a biscyclohexyldioxy group, a pinanedioxy group, or a 1,2-phenylenedioxy group. The number of carbon atoms in the substituted or C1-C6 alkoxy group is preferably 1 to 5, more preferably 1 to 4. The number of carbon atoms in the alkyl group in the phenoxy group is preferably 1 to 5, more preferably 1 to 4.

[0023] Ar 2 -B(R 1 )(R 2 Preferred compounds represented by the formula: Ar are substituted or unsubstituted arylboronic acids that can be used in Suzuki coupling. 2 , R 1 and R 2 are as described above. Examples of such arylboronic acids that can be used include phenylboronic acid, 1-naphthylboronic acid, and 2-naphthylboronic acid. Examples of substituents in arylboronic acids include lower alkyl groups (e.g., methyl, ethyl, propyl, and tert-butyl), lower alkoxy groups (e.g., methoxy, ethoxy, and propoxy), aromatic hydrocarbon groups having 6 to 24 carbon atoms (e.g., 4-phenylphenyl and 3-phenylphenyl), halogen atoms (e.g., fluorine and chlorine atoms), and trifluoromethyl groups.

[0024] <Oxygen atmosphere> By carrying out the reaction step (A) in an oxygen atmosphere, the target compound can be obtained in a high yield in a short time. In this specification, "in an oxygen atmosphere" means an atmosphere containing oxygen, and the types of other gases constituting the atmosphere, the oxygen concentration in the atmosphere, and the atmospheric pressure are not particularly limited. Without being bound by a particular theory, it is believed that by carrying out the reaction in an oxygen atmosphere, palladium in the catalyst is partially oxidized, and when this is reduced in the presence of boronic acid, the three-dimensional structure of the catalyst changes from its original structure, generating chemical species that are more active than the original catalyst, and these generated chemical species become catalytic active sites, accelerating the reaction.

[0025] Examples of other gases constituting the atmosphere include inert gases such as helium, nitrogen, and argon, which may be used singly or in combination of two or more. Among these, nitrogen or argon is preferred as the other gas from the viewpoint of safety, that is, low risk of ignition due to mixing with oxygen, and from the viewpoint of being less likely to diffuse outside the reactor because its specific gravity is equal to or greater than that of oxygen.

[0026] The oxygen concentration in an "oxygen atmosphere" is not particularly limited and can be selected from any concentration. When an organic solvent is used as a solvent in the reaction, the oxygen concentration is preferably 0.001% by volume to 50% by volume, more preferably 0.01% by volume to 40% by volume, even more preferably 0.1% by volume to 30% by volume, and even more preferably 1% by volume to 25% by volume, from the viewpoint of safety in order to promote dissolution of oxygen into the solvent and to avoid ignition, etc.

[0027] The pressure of the gas constituting the oxygen atmosphere is not particularly limited and can be selected as desired. From the viewpoint of safety, which promotes dissolution of oxygen into the solvent while avoiding ignition, the pressure is preferably 0.1 to 10 atmospheres, more preferably 0.3 to 5 atmospheres, and even more preferably 0.5 to 3 atmospheres.

[0028] For the above reasons, in the present embodiment, the "oxygen atmosphere" is preferably an ordinary air atmosphere or an oxygen atmosphere in which nitrogen or argon is mixed with air in any ratio, since this does not complicate the reaction operation. In this preferred embodiment, ordinary air is used, so the oxygen concentration in the oxygen atmosphere is 25% by volume or less.

[0029] <Inorganic additives> In this embodiment, it is preferable to have an inorganic additive present in the reaction system in the reaction step (A). Examples of the inorganic additive include celite and neutral silica. Addition of this inorganic additive tends to improve the overall reaction yield. When the inorganic additive is not added, it has been observed that the catalyst aggregates and adheres to the walls of the reaction vessel. Without being bound by any particular theory, it is believed that the addition of the inorganic additive causes the catalyst to sink in the reaction vessel, and that the inorganic additive interacts with the catalyst, breaking up the catalyst aggregation and preventing the catalyst from adhering to the walls of the reaction vessel, thereby improving the overall reaction yield. Among these, it is preferable to use Celite, which is chemically more inactive.

[0030] Commercially available inorganic additives include amorphous silicates containing 80 to 95% by weight of SiO, the main component, such as Radiolite #100, Radiolite #200, Radiolite #500, Radiolite #600, Radiolite #900, Zemulite Super M, Zemulite Super 1, Zemulite Super 56, Zemulite Super 2, Celite 501, Celite 503, Celite 535, Celite 545, Hyflo Super Cel, Standard Super Cel, and Filter Cel. Aluminum silicates containing approximately 70% by weight of SiO, the main component, include Topco #31 and Topco #34. These additives may be used alone or in combination. Among these, Standard Super Cel, which has a large surface area, is particularly preferred.

[0031] The inorganic additive is preferably added in an amount of 1 to 200 times by mass relative to the catalyst used in reaction step (A). When the catalyst used in reaction step (A) is recovered and reused (reused) in the reaction, the amount of inorganic additive added refers to the mass of the recovered catalyst or the catalyst contained in the catalyst-containing material. If the amount of inorganic additive added is within the above range, high catalytic activity can be maintained and the overall reaction yield can be improved. The amount of inorganic additive added is more preferably 2 to 180 times, even more preferably 5 to 160 times, and even more preferably 10 to 150 times, relative to the catalyst.

[0032] <Solvent> The reaction step (A) is preferably carried out in the presence of a solvent. The solvent is preferably one that does not interfere with the intended reaction and has high solubility for the raw material compounds used in the reaction. Specifically, at least one selected from the group consisting of water, lower alcohols such as methanol and ethanol, trifluoroacetic acid, acetone, 1,2-dimethoxyethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, benzene, toluene, ethyl acetate, 1,4-dioxane, dichloromethane, chloroform, and 1,2-dichloroethane is preferred. Among these, water and water-soluble solvents are preferred because of their high solubility in the base described below, and ethanol is particularly preferred.

[0033] As mentioned above, water can be used as a solvent. Generally, water is thought to reduce catalytic activity. However, when a base is used in the reaction step (A) as described below, the base has high solubility in water, and dissolving the base has the effect of promoting the reaction. Furthermore, the present inventors have hypothesized that inorganic substances, such as the base used in the reaction or a reaction product with a salt, may clog the nanopores of the intermetallic compound-supported ZrC catalyst, which may be a factor in reducing catalytic activity during the reaction or when the catalyst is reused. In particular, they have found that using an aqueous solvent, such as water or ethanol, when reusing the catalyst eliminates clogging of the nanopores of the ZrC catalyst, i.e., has the effect of cleaning the catalyst, restoring high catalyst activity.

[0034] When water is used as a solvent, there are no particular limitations, and any of pure water, distilled water, ion-exchanged water, and tap water can be used. When the solvent contains water, the amount of water is preferably 1 mass % or more of the total solvent. The presence of water in this range can promote the reaction in reaction step (A) and maintain high catalytic activity during reuse.

[0035] <base> In the reaction step (A), the reaction is preferably carried out in the presence of a base. As the base, it is preferable to use an alkali metal salt or alkaline earth metal salt of which the pKa of the conjugate acid is 1 or more and 20 or less. When the pKa of the conjugate acid is within the above range, the overall reaction yield can be improved. Furthermore, when the catalyst is reused, the recovered catalyst can be washed more effectively, and the catalytic activity can be further maintained even when the recovered catalyst is used repeatedly. Specifically, at least one selected from the group consisting of potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, trisodium phosphate, tripotassium phosphate, sodium hydrogen phosphate, and potassium hydrogen phosphate can be used. Potassium carbonate is preferably used.

[0036] The base was used in a concentration of 0.01 mol / m3 More than 12mol / m 3 It is preferable to add the base as an aqueous base solution containing the following. If the molar concentration of the aqueous base solution is within the above range, the overall reaction yield can be improved. When the base is added as an aqueous base solution, the molar concentration is more preferably 0.1 mol / m 3 More than 10mol / m 3 or less, more preferably 0.2 mol / m 3 More than 8mol / m 3 or less, even more preferably 0.5 mol / m 3 More than 6mol / m 3 The following is the result.

[0037] <Reaction conditions> The reaction temperature in reaction step (A) can be appropriately selected depending on the raw material compounds used, but is preferably 10°C or higher and 200°C or lower, more preferably 20°C or higher and 100°C or lower, and even more preferably 40°C or higher and 90°C or lower. The reaction time in the reaction step (A) can be appropriately selected depending on the raw material compounds used, but is preferably 1 hour or more and 20 hours or less, more preferably 2 hours or more and 10 hours or less, and even more preferably 3 hours or more and 7 hours or less. As will be described later, when the catalyst used in step (A) is recovered and the recovered catalyst is used to carry out the reaction, the reaction time can be appropriately changed depending on the number of times of recycling and the reaction conditions. For example, the reaction time in the first reuse cycle is preferably 2 hours or more and 60 hours or less, more preferably 3 hours or more and less than 60 hours, and even more preferably 4 hours or more and 57 hours or less, and the reaction time in the second and subsequent reuse cycles is preferably 10 hours or more and 60 hours or less, more preferably 10 hours or more and 57 hours or less. When the reaction temperature and reaction time in step (A) are within the above ranges, the target compound can be obtained efficiently in an excellent yield.

[0038] <Catalyst reuse> In this embodiment, the catalyst used in the reaction step (A) can be recovered and reused in the reaction step (A). Here, the method for recovering the catalyst, the method for regenerating the catalyst, and the method for carrying out the reaction step (A) when reusing the catalyst are not particularly limited. Examples of methods for recovering the catalyst include a method in which, after the reaction is completed, the catalyst is separated from the solvent by suction filtration or pressure filtration using a filter, and a method in which the supernatant solvent is removed by decantation or the like.

[0039] The recovered catalyst may be reused without any special operation, or may be subjected to a specific regeneration operation, such as regeneration by a wet process or a dry process. An example of regeneration by a wet process is a process in which the intermetallic compound-supported ZrC catalyst used in the reaction step (A) is recovered after the reaction is completed, and washed in a solvent.

[0040] Specifically, one aspect of the wet process is a regeneration step in which the recovered catalyst is washed by mixing a solvent in an amount equal to or greater than 1 part by mass of the catalyst and stirring at a temperature of 0°C to 150°C for 1 minute to 20 hours. This step allows raw materials, additives, reactants, by-products, and the like that have accumulated on the catalyst due to the reaction to be washed away. Therefore, this is more preferable than a recovered catalyst in which the spent catalyst is filtered and then simply dried, as it allows the catalyst activity to be maintained even after the second cycle. The solvent used in this regeneration step (wet process) can be the same as those listed in the above reaction step (A). Among these, it is preferable for the solvent to contain water. When the solvent contains water, it is preferable that the water content of the total solvent is 1 mass% or more. By including water in the above range, the subsequent reaction step (A), in which the regenerated catalyst is reused, can be carried out efficiently and with a higher yield. One of the reasons for this, without being bound by any particular theory, is thought to be that impurities such as inorganic substances that have clogged the catalyst nanoporosity can be washed away, thereby maintaining high catalytic activity.

[0041] The solvent in the regeneration step (wet process) may contain a base. The base may be the same as those listed in the above-mentioned reaction step (A), and the preferred range is also the same. If the molar concentration of the aqueous base solution is within the range described in the reaction step (A), the activity of the catalyst can be maintained high, and the overall reaction yield can be improved. The catalyst regeneration temperature in the regeneration step (wet process) is 0°C or higher and 150°C or lower, preferably 10°C or higher and 130°C or lower, more preferably 20°C or higher and 120°C or lower, even more preferably 30°C or higher and 110°C or lower, still more preferably 40°C or higher and 100°C or lower, and particularly preferably 50°C or higher and 90°C or lower. In the regeneration step (wet process), the time for regenerating the catalyst is from 1 minute to 20 hours, preferably from 3 minutes to 15 hours, more preferably from 5 minutes to 13 hours, even more preferably from 7 minutes to 11 hours, still more preferably from 8 minutes to 10 hours, and particularly preferably from 9 minutes to 9 hours. In the regeneration step (wet process), when the conditions for regenerating the catalyst are within the above range, the catalyst can be regenerated more efficiently.

[0042] The regeneration by the dry process includes a step of recovering the intermetallic compound-supported ZrC catalyst used in the reaction step (A) after the reaction is completed, and performing a heat treatment step. If the heat treatment temperature is low, the decomposition of organic compounds deposited in the catalyst will not proceed sufficiently, resulting in insufficient catalyst regeneration and a decrease in the yield of the target product in reaction step (A) using the regenerated catalyst. The heat treatment temperature is usually 300°C or higher, preferably 350°C or higher, more preferably 400°C or higher, even more preferably 500°C or higher, still more preferably 600°C or higher, and even more preferably 700°C or higher. There is no particular upper limit, but from the viewpoint of maintaining catalytic activity, it is preferably 1500°C, more preferably 1100°C, and even more preferably 1000°C.

[0043] The method for carrying out reaction step (A) using the recycled catalyst is the same as the method for reaction step (A) described above, and the preferred solvent, base, conditions under an oxygen atmosphere, reaction temperature, etc. are also the same unless otherwise specified. The reaction in reaction step (A) using the recycled catalyst is not limited in any way as long as it uses a used recovered catalyst. For example, it may be the same as or different from the reaction in reaction step (A), but it is preferable that it is the same from the viewpoint of reaction economy.

[0044] <Application of mechanochemical method> The catalyst of the present invention can also be applied to mechanochemical processes. Mechanochemical processes are organic synthesis reaction methods in which mechanical energy is applied to solid reactant materials by means of grinding, shearing, impact, compression, or the like to activate the materials and directly contact them. That is, the reaction process using the intermetallic compound-supported ZrC catalyst can be carried out in a solid state using no solvent or a small amount of solvent by applying mechanical force in a disperser such as a ball mill to produce the target compound. Because the intermetallic compound-supported ZrC catalyst is mechanically strong, it is less likely to change shape due to crushing. Furthermore, when a substrate that is poorly soluble in a solvent is used in reaction step (A), the reaction may be difficult to proceed in the solvent. However, by applying the mechanochemical process, the target compound can be obtained. In this embodiment, the term "small amount of solvent" refers to the use of a solvent whose mass is equal to or less than the total mass of the raw materials used in the reaction. [Example]

[0045] The present invention will be explained in more detail below by way of examples, but the present invention is not limited to the following examples as long as it does not depart from the gist of the invention. In the examples, "parts" and "%" are by mass unless otherwise specified. The yield was calculated by sampling the filtrate or the supernatant of the recovered reaction solution, subjecting it to HPLC measurement, and comparing the peak area with that of a sample separately obtained by HPLC measurement using commercially available 4-methylbiphenyl as a standard.

[0046] Comparative Example 1 (Reaction under nitrogen) 4-Bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (5 mL) were added to a 60 mL test tube and completely dissolved. To this was added ZrPd3-ZrC catalyst (5 mg) and an aqueous solution of potassium carbonate (0.343 g, 2.5 mmol) dissolved in water (1.24 mL). After purging the test tube with nitrogen, the mixture was heated to 80°C under a nitrogen stream and stirred for 6 hours. After filtration through Celite, the desired 4-methylbiphenyl was obtained in 59% yield. The results are shown in Table 1.

[0047] Comparative Example 2 (Reaction under nitrogen, with recycling process) 4-Bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (4 mL) were added to a 60 mL test tube and completely dissolved. To this was added a potassium carbonate solution prepared by dissolving ZrPd3-ZrC catalyst (5 mg), Celite No. 545 (0.1 g), and potassium carbonate (0.343 g, 2.5 mmol) in water (2 mL). After purging the atmosphere in the test tube with nitrogen, the reaction mixture was heated to 80 °C under a nitrogen stream and stirred for 5 hours. The reaction mixture was then allowed to stand for 5 minutes, the supernatant was removed, and the remaining solid was washed with a 2:1 ethanol / water mixture. The resulting wash solution was combined with the reaction mixture to obtain the desired 4-methylbiphenyl in 94% yield. The remaining solid was completely dissolved by adding 4-bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (4 mL). Potassium carbonate (0.343 g, 2.5 mmol) dissolved in water (2 mL) was added to the resulting solution. The atmosphere in the test tube was replaced with nitrogen, and the reaction was carried out by heating to 80°C under a nitrogen stream. The progress of the reaction was monitored using HPLC, and it took 44 hours for the production of the desired 4-methylbiphenyl to reach its maximum. After stirring for 44 hours, the mixture was filtered through Celite, and the desired 4-methylbiphenyl was obtained in 84% yield. The results are shown in Table 1.

[0048] Example 1 (Reaction under air) 4-Bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (5 mL) were added to a 60 mL test tube and completely dissolved. To this was added ZrPd3-ZrC catalyst (5 mg) and an aqueous solution of potassium carbonate (0.343 g, 2.5 mmol) dissolved in water (1.24 mL). The mixture was heated to 80°C under air and stirred for 6 hours. After filtration through Celite, the desired 4-methylbiphenyl was obtained in 92% yield. The results are shown in Table 1.

[0049] Example 2 (Reaction under air, with recycling process) 4-Bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (4 mL) were added to a 60 mL test tube and completely dissolved. To this was added a potassium carbonate solution prepared by dissolving ZrPd3-ZrC catalyst (5 mg), Celite No. 545 (0.1 g), and potassium carbonate (0.343 g, 2.5 mmol) in water (2 mL). The mixture was heated to 80 °C under air and stirred for 5 hours. The reaction mixture was then allowed to stand for 5 minutes. The supernatant was removed, and the remaining solid was washed with a 2:1 ethanol / water mixture. The resulting wash solution was added to the reaction mixture, affording the desired 4-methylbiphenyl in 94% yield. The remaining solid was completely dissolved by adding 4-bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (4 mL). Potassium carbonate (0.343 g, 2.5 mmol) dissolved in water (2 mL) was added to the resulting solution. The reaction was heated to 80 °C under air. HPLC analysis revealed that it took 22 hours for the production of the desired 4-methylbiphenyl to reach its maximum. After stirring for 22 hours, the reaction mixture was allowed to stand for 5 minutes. The supernatant was removed, and the remaining solid was washed with a 2:1 ethanol / water mixture. The resulting wash was added to the reaction mixture, affording the desired 4-methylbiphenyl in 86% yield. The remaining solid was completely dissolved by adding 4-bromotoluene (0.085 g, 0.5 mmol), phenylboronic acid (0.097 g, 0.8 mmol), and ethanol (4 mL). Potassium carbonate (0.343 g, 2.5 mmol) dissolved in water (2 mL) was added to the resulting solution. The reaction was heated to 80°C under air. The progress of the reaction was monitored using HPLC, and it took 40 hours for the production of the desired 4-methylbiphenyl to reach its maximum. After stirring for 40 hours, the mixture was filtered through Celite, and the desired 4-methylbiphenyl was obtained in 87% yield. The results are shown in Table 1.

[0050] [Table 1]

[0051] From the results of Comparative Example 1 and Example 1, it was confirmed that the yield was improved by carrying out the reaction step under an oxygen atmosphere. From the results of Comparative Example 2 and Example 2, which have a recycling step using a recovered catalyst after step (A), it was confirmed that by carrying out the reaction under an oxygen atmosphere in the recycling step, the reaction time required to reach a comparable yield can be significantly shortened. Furthermore, from Example 2, it was confirmed that by carrying out the reaction under an oxygen atmosphere, a higher yield than that of Comparative Example 2 can be achieved in a shorter reaction time even in the second recycling step. These results confirmed that, in a reaction using an intermetallic compound-supported zirconium carbide catalyst, in which particles of an intermetallic compound of palladium and zirconium are supported on zirconium carbide having a nanoporous structure, carrying out the reaction in an oxygen atmosphere improved catalytic activity. The reactions in the comparative examples and examples are Suzuki coupling reactions, which are usually carried out in an inert atmosphere. However, according to the present invention, by carrying out the reaction in an oxygen atmosphere, the target reactant can be obtained in a short time and with a high yield, and the target reactant can also be obtained efficiently in a utilization process when a recovered catalyst is used.

Claims

1. A method for producing a compound, comprising: a reaction step (A) using an intermetallic compound-supported zirconium carbide as a catalyst, the intermetallic compound being formed by supporting particles of an intermetallic compound of palladium and zirconium on zirconium carbide having a nanoporous structure; The method for producing a compound, wherein the reaction step (A) is carried out under an oxygen atmosphere.

2. The method according to claim 1 , wherein the reaction step (A) is a reaction represented by formula (1): 【Chemical 1】 [In formula (1), Ar １ and Ar ２ each independently represents a substituted or unsubstituted aromatic hydrocarbon group or heteroaromatic hydrocarbon group, X represents at least one selected from the group consisting of halogen, mesyl group, tosyl group, perfluoroalkylsulfonyl group, diazonio group, and triflyl group, R １ and R ２ are each independently a hydroxyl group, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms, or a phenoxy group which may have an alkyl group having 1 to 6 carbon atoms, and R １ and R ２ may be linked to each other to form a ring as an ethylenedioxy group, a 2,3-dimethylbutane-2,3-dioxy group, a 2,2-dimethylpropane-1,3-dioxy group, a 3,4-diethylhexane-3,4-dioxy group, a biscyclohexyldioxy group, a pinanedioxy group, or a 1,2-phenylenedioxy group.]

3. The manufacturing method according to claim 1 or 2, wherein the oxygen atmosphere contains oxygen in an amount of 1% by volume or more and 25% by volume or less.

4. The method according to claim 1 or 2, wherein in the reaction step (A), an inorganic additive is coexisted in an amount of 1 to 200 times by mass relative to the catalyst.

5. The method according to claim 1 or 2, wherein the reaction step (A) is carried out in the presence of a solvent.

6. The method according to claim 5 , wherein the solvent comprises water.

7. The method according to claim 6, wherein the content of water in the total solvent is 1 mass % or more.

8. The method according to claim 6, wherein the reaction step (A) is carried out in the presence of a base.

9. The base is added to water at a concentration of 0.01 mol / m ３ More than 12mol / m ３ 9. The method of claim 8, comprising:

10. The method according to claim 8 , wherein the base comprises an alkali metal salt or an alkaline earth metal salt having a conjugate acid with a pKa of 1 or more and 20 or less.

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