Hydrocracking catalyst for carbon-heteroatom bond, method for producing said hydrocracking catalyst, and method for hydrocracking carbon-heteroatom bond

Abstract

[Problem] To provide a hydrocracking reaction catalyst in which a strong acid is not used, and which exhibits excellent catalytic activity equal to or higher than that of catalysts in the prior art even when the amount of palladium is reduced compared with palladium catalysts in the prior art. [Solution] A hydrocracking catalyst for hydrocracking the carbon-heteroatom bond of a substrate organic compound containing said carbon-heteroatom bond, the hydrocracking catalyst comprising a carbon-based carrier that carries at least: a palladium catalyst; and a phosphoric acid compound and / or an acetic acid compound.

Description

CATALYST FOR HYDROCRACKING OF CARBON-HETEROATOM BOND, METHOD FOR PRODUCING THE SAME, AND METHOD FOR HYDROCRACKING CARBON-HETEROATOM BOND

[0001] This patent application claims priority based on Japanese Patent Application No. 2023-188316 filed on November 2, 2023, the entire disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to catalysts for the hydrocracking of carbon-heteroatom bonds, methods for their preparation, and methods for hydrocracking carbon-heteroatom bonds.

[0003] In the field of organic synthesis, the introduction and deprotection of various protecting groups is extremely important for synthesizing a target compound, and the carbon-heteroatom bond is known to be a structure that facilitates the introduction and deprotection of various protecting groups.

[0004] For the deprotection of a protecting group once introduced (e.g., hydrogenolysis of a benzyl group), catalytic hydrogen reduction using a palladium / carbon catalyst is mainly used, but there is a problem that the deprotection reaction does not proceed unless a large amount of palladium is added as a catalyst. Therefore, further improvements are being considered for such deprotection reactions, as the cost and yield of the palladium catalyst are insufficient.

[0005] For example, Patent Document 1 proposes a method in which hydrogen is reacted in the presence of a palladium catalyst and an amine having one nitrogen atom, so that the amine having one nitrogen atom modifies the palladium catalyst, and the modified palladium catalyst selectively hydrogenates a protecting group (benzyl group).

[0006] Furthermore, Patent Document 2 proposes a hydrocracking catalyst in which a Bronsted acid catalyst and a palladium catalyst are brought into contact with each other in a reactor.

[0007] JP 2017-197484 A International Publication No. 2021 / 251248

[0008] However, the method proposed in Patent Document 1 in which the surface of a palladium catalyst is coated with an amine compound to adjust the catalytic activity has the problem that the catalytic activity decreases due to poisoning.

[0009] Furthermore, the hydrogenolysis catalyst proposed in Patent Document 2 uses activated carbon, which has been treated with a strong acid such as nitric acid or sulfuric acid to impart an acidic functional group, as a Bronsted acid catalyst, mixed with a palladium carbon catalyst. However, the two types of catalysts are deactivated at different times, and the use of a strong acid during production poses problems related to manufacturability, such as the need to deal with the heat of dilution with the water in the hydrous carbon and waste liquid treatment.

[0010] In view of the above-mentioned problems, an object of the present disclosure is to provide a hydrocracking catalyst that does not use a strong acid and has excellent catalytic activity equivalent to or greater than that of conventional palladium catalysts, even when the amount of palladium is reduced compared to conventional palladium catalysts.

[0011] As a result of extensive research, the present inventors have found that by supporting a phosphate compound or an acetate compound in addition to palladium on a carbon-based support, a hydrocracking catalyst having excellent catalytic activity can be obtained without using a strong acid. The present disclosure is based on this finding.

[0012] One embodiment of the present disclosure provides a hydrogenolysis catalyst for hydrogenolysis of a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the hydrogenolysis catalyst comprising a carbon-based support on which at least a palladium catalyst and at least one of a phosphoric acid compound and an acetate compound are supported.

[0013] According to the present disclosure, it is possible to provide a hydrocracking catalyst that has excellent catalytic activity equivalent to or greater than that of conventional catalysts, even when a strong acid is not used and the amount of palladium is reduced compared to conventional palladium catalysts.

[0014] [Hydrogenolysis catalyst] One embodiment of the present disclosure is a hydrocracking catalyst for hydrocracking a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond. One feature of the hydrocracking catalyst is that it comprises a carbon-based support carrying at least a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound. The hydrocracking catalyst of the present disclosure is described in detail below.

[0015] (Palladium Catalyst) In the hydrocracking catalyst of the present disclosure, the palladium catalyst is used as a hydrogenation catalyst. The palladium catalyst may contain palladium element as a catalytic species, and may contain palladium itself or a compound containing palladium (palladium compound). Known compounds such as particles and various alloys may be used as the palladium catalyst.

[0016] Examples of palladium compounds include tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium chloride, palladium acetate, tris(dibenzylideneacetone)dipalladium, bis(dibenzalacetone)palladium, bis[4-(N,N-dimethylamino)phenyl]di-tert-butylphosphinepalladium chloride, bis(di-tert-butylprenylphosphine)palladium chloride, and bis(di-tert-crotylphosphine)palladium dichloride.

[0017] The amount of palladium catalyst contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved, but may be, for example, 1 to 20 parts by mass, preferably 1.5 to 18 parts by mass, more preferably 2 to 15 parts by mass, and even more preferably 3 to 13 parts by mass, per 100 parts by mass of the hydrocracking catalyst (dry basis). The amount of elemental palladium contained in the hydrocracking catalyst is also not particularly limited as long as the object of the present disclosure can be achieved, but may be, for example, 1 to 20 parts by mass, preferably 1.5 to 18 parts by mass, more preferably 2 to 15 parts by mass, and even more preferably 3 to 13 parts by mass, per 100 parts by mass of the hydrocracking catalyst (dry basis). Setting the amount of palladium catalyst or elemental palladium within the above range may ensure a sufficient contact area between the palladium catalyst and the substrate organic compound, thereby improving reactivity.

[0018] According to one embodiment of the present disclosure, the palladium catalyst is palladium itself (ie, elemental palladium).

[0019] (Phosphate Compound, Acetate Compound) In the present disclosure, the term "phosphate compound" refers to a compound having at least a hydroxyl group bonded to a phosphorus atom. The phosphate compound may be an organic phosphate compound or an inorganic phosphate compound.

[0020] Examples of the phosphate compound include, but are not limited to, inorganic phosphate compounds such as phosphoric acid (orthophosphoric acid), phosphorous acid, hypophosphorous acid, pyrophosphoric acid, metaphosphoric acid, and diphosphoric acid pentoxide; and organic phosphate compounds such as organic derivatives of phosphinic acid and phosphonic acid. According to one embodiment of the present disclosure, the phosphate compound is an inorganic phosphate compound, and preferably has an acid dissociation constant pKa (H ２ O) is one or more inorganic phosphate compounds. According to a preferred embodiment of the present disclosure, the phosphate compound includes at least one selected from the group consisting of phosphoric acid (orthophosphoric acid), pyrophosphoric acid, metaphosphoric acid, and diphosphoric acid pentoxide. According to a more preferred embodiment of the present disclosure, the phosphate compound includes at least phosphoric acid (orthophosphoric acid).

[0021] In the present disclosure, the term "acetate compound" refers to "CR ３ —C(O)OH” (wherein each R is independently hydrogen, C １－６ means a compound having the structure of (meaning alkyl or halogen).

[0022] In this disclosure, １－６ "Alkyl" means a straight or branched chain alkyl having 1 to 6 carbon atoms, including, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, and the like.

[0023] In the present disclosure, "halogen" includes, for example, fluorine, chlorine, bromine, iodine, and the like.

[0024] Examples of acetic acid compounds include, but are not limited to, acetic acid, trifluoroacetic acid, monochloroacetic acid, dichloroacetic acid, dimethylacetic acid, and the like.

[0025] According to one embodiment of the present disclosure, the acetic acid compound has an acid dissociation constant pKa (H ２O) is one or more acetic acid compounds. According to a preferred embodiment of the present disclosure, the acetic acid compound includes at least one selected from the group consisting of acetic acid, monochloroacetic acid, dichloroacetic acid, and dimethylacetic acid. According to a more preferred embodiment of the present disclosure, the acetic acid compound includes at least acetic acid.

[0026] According to one embodiment of the present disclosure, the hydrocracking catalyst of the present disclosure contains at least a phosphoric acid compound. According to a preferred embodiment of the present disclosure, the hydrocracking catalyst of the present disclosure contains at least phosphoric acid (orthophosphoric acid). A phosphoric acid compound (preferably phosphoric acid) is advantageous over other acids in that it does not emit an odor or change over time due to decomposition during storage.

[0027] The amount of at least one of the phosphoric acid compound and the acetic acid compound contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved, but may be, for example, 1 to 20 parts by mass, preferably 1.5 to 15 parts by mass, more preferably 2 to 10 parts by mass, and even more preferably 3 to 8 parts by mass, per 100 parts by mass of the hydrocracking catalyst (dry basis). When the hydrocracking catalyst contains a phosphoric acid compound, the amount of elemental phosphorus contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved, but may be, for example, 0.25 to 5 parts by mass, preferably 0.4 to 4 parts by mass, more preferably 0.5 to 2.5 parts by mass, and even more preferably 0.7 to 2 parts by mass, per 100 parts by mass of the hydrocracking catalyst (dry basis).

[0028] The ratio of the palladium catalyst to at least one of the phosphoric acid compound and the acetic acid compound contained in the hydrocracking catalyst (palladium catalyst:at least one of the phosphoric acid compound and the acetic acid compound) is not particularly limited as long as the object of the present disclosure can be achieved. For example, the ratio may be 1:20 to 20:1, preferably 1:10 to 10:1, more preferably 1:5 to 5:1, and even more preferably 2:1 to 1:2, based on the parts by mass of these compounds contained in the hydrocracking catalyst.

[0029] When the hydrogenation catalyst contains a phosphoric acid compound, the ratio of elemental palladium to elemental phosphorus (elemental palladium:elemental phosphorus) contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved. For example, the ratio may be 1:10 to 40:1, preferably 1:5 to 20:1, more preferably 1:3 to 10:1, and even more preferably 1:1 to 5:1, based on the parts by mass of these elements contained in the hydrocracking catalyst.

[0030] (Carbon-based Support) The hydrocracking catalyst of the present disclosure comprises a carbon-based support supporting at least a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound. The carbon-based support is not particularly limited as long as it is capable of supporting a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound. Examples of carbon-based supports include, but are not limited to, activated carbon, pulverized activated carbon, mesoporous carbon, graphene, carbon nanotubes, glassy carbon (GC), fine carbon, carbon black, graphite, carbon fiber, and the like. According to one embodiment of the present disclosure, the carbon-based support comprises at least one selected from the group consisting of activated carbon, mesoporous carbon, graphene, and carbon nanotubes.

[0031] The specific surface area of ​​the carbon-based support is not particularly limited as long as the object of the present disclosure can be achieved. ３ / g or more, preferably 10m ３ / g or more, more preferably 100m ３ / g or more, more preferably 300m ３ The upper limit of the specific surface area of ​​the carbon-based support may be, for example, 3000 m ３ / g or less, preferably 2000m ３ / g or less, more preferably 1500m ３ / g or less, more preferably 1000m ３ / g or less.

[0032] The amount of the carbon-based support contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved. For example, the amount may be 10 to 50 parts by mass, preferably 15 to 50 parts by mass, more preferably 25 to 50 parts by mass, and even more preferably 35 to 50 parts by mass, per 100 parts by mass of the hydrocracking catalyst (dry basis).

[0033] The ratio of the palladium catalyst to the carbon-based support (palladium catalyst:carbon-based support) contained in the hydrocracking catalyst is not particularly limited as long as the object of the present disclosure can be achieved. For example, the ratio may be 1:50 to 2:1, preferably 1:30 to 1:1, more preferably 1:20 to 1:3, and even more preferably 1:10 to 1:4, based on the parts by mass of these components contained in the hydrocracking catalyst.

[0034] The ratio of at least one of a phosphoric acid compound and an acetic acid compound to a carbon-based support contained in the hydrocracking catalyst (at least one of a phosphoric acid compound and an acetic acid compound:carbon-based support) is not particularly limited as long as the object of the present disclosure can be achieved. For example, the ratio may be 1:50 to 2:1, preferably 1:30 to 1:1, more preferably 1:20 to 1:3, and even more preferably 1:10 to 1:4, based on the parts by mass of these compounds contained in the hydrocracking catalyst.

[0035] The hydrocracking catalyst of the present disclosure may contain water. The hydrocracking catalyst of the present disclosure containing water is advantageous in terms of preventing the catalyst from scattering and preventing fire during use. When the hydrocracking catalyst of the present disclosure contains water, the water content may be, for example, 5 to 70 parts by mass, more preferably 20 to 60 parts by mass, and even more preferably 45 to 55 parts by mass per 100 parts by mass of the hydrocracking catalyst.

[0036] The hydrocracking catalyst of the present disclosure may have other components supported on the carbon-based support, provided that the object of the present disclosure is not impaired. Examples of such other components include, but are not limited to, noble metal elements other than palladium (e.g., platinum, ruthenium, etc.) or compounds thereof, and compounds having functional groups such as sulfo, carboxy, and amino groups.

[0037] The hydrocracking catalyst of the present disclosure may contain other components (e.g., other catalysts having hydrocracking ability, co-catalysts that promote the hydrocracking reaction, etc.) in addition to the palladium catalyst and the carbon-based support on which at least one of a phosphoric acid compound and an acetate compound is supported, as long as the object of the present disclosure is not impaired.

[0038] (Substrate Organic Compounds Containing Carbon-Heteroatom Bonds) The hydrocracking catalysts of the present disclosure are capable of hydrocracking carbon-heteroatom bonds in substrate organic compounds containing such bonds.

[0039] As used in the present disclosure, the term "carbon-heteroatom bond" refers to a bond formed between a carbon atom and an atom other than a carbon atom. Examples of atoms other than a carbon atom include, but are not limited to, a nitrogen atom, an oxygen atom, a sulfur atom, a phosphorus atom, a metal atom, and the like, with a nitrogen atom and an oxygen atom being preferred. Therefore, examples of carbon-heteroatom bonds include a carbon-nitrogen bond, a carbon-oxygen bond, a carbon-sulfur bond, a carbon-phosphorus bond, and a carbon-metal atom bond. From the viewpoint of ease of occurrence of a hydrogenolysis reaction, the carbon-heteroatom bond is preferably a carbon-nitrogen bond or a carbon-oxygen bond, and more preferably a carbon-nitrogen bond.

[0040] The carbon-heteroatom bond may be a single bond, a double bond, or a triple bond. According to one embodiment of the present disclosure, the carbon-heteroatom bond is a single bond.

[0041] The term "substrate organic compound containing a carbon-heteroatom bond" (hereinafter simply referred to as "substrate organic compound") used in the present disclosure is not particularly limited, as long as it is an organic compound that contains at least one carbon-heteroatom bond in the molecule and can serve as a substrate for a hydrogenolysis reaction. The substrate organic compound may be partially or entirely chain-like (e.g., linear or branched) or cyclic. The carbon-carbon bond in the substrate organic compound may be a single bond, or may contain one or more double and / or triple bonds. In addition, in the substrate organic compound, one or more hydrogen atoms bonded to a carbon atom may be substituted with any substituent (e.g., an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an alkoxy group, a halogen group, a carboxyl group, an aldehyde group, a hydroxy group, an amino group, or a phenyl group, each of which may be substituted with one or more optional substituents). One or more carbon atoms constituting the substrate organic compound may be substituted with a heteroatom (e.g., an oxygen atom, a nitrogen atom, or a sulfur atom).

[0042] The hydrogenolysis catalyst of the present disclosure can be used for the purpose of deprotection reactions of protecting groups that protect highly reactive sites in a molecule from reaction with other sites. Therefore, the substrate organic compound may be a compound in which a protecting group is coordinated to the heteroatom site in a carbon-heteroatom bond. Examples of the "protecting group" in the present disclosure include, but are not limited to, aralkyl groups (e.g., benzyl group, 2-methylbenzyl group, 3-methylbenzyl group, 4-methylbenzyl group, 2-chlorobenzyl group, 3-chlorobenzyl group, 4-chlorobenzyl group, 2-bromobenzyl group, 3-bromobenzyl group, 4-bromobenzyl group, 2-fluorobenzyl group, 3-fluorobenzyl group, 4-fluorobenzyl group, 2-nitrobenzyl group, 3-nitrobenzyl group, 4-nitrobenzyl group, 2-methoxybenzyl group, 3-methoxybenzyl group, 4-methoxybenzyl group, diphenylmethyl group, etc.), aralkyloxycarbonyl groups (e.g., benzyloxycarbonyl group, 2 ... protecting groups having an aromatic ring structure such as aralkyloxycarbonyl groups (e.g., nitrobenzyloxycarbonyl group, 3-nitrobenzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, 2-bromobenzyloxycarbonyl group, 3-bromobenzyloxycarbonyl group, 4-bromobenzyloxycarbonyl group, 2-methoxybenzyloxycarbonyl group, 3-methoxybenzyloxycarbonyl group, 4-methoxybenzyloxycarbonyl group), alkyloxycarbonyl groups (e.g., t-butyloxycarbonyl group, t-amyloxycarbonyl group), and the like; trialkylsilylcarbonyl groups (e.g., trimethylsilyl group, t-butyldimethylsilyl group), and the like. The protecting group is preferably a protecting group having an aromatic ring structure, more preferably an aralkyl group or an aralkyloxycarbonyl group, even more preferably a benzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group, a 4-methoxybenzyl group or a benzyloxycarbonyl group, and still more preferably a benzyl group.

[0043] According to one embodiment of the present disclosure, the carbon-heteroatom bond is a carbon-heteroatom bond adjacent to an aromatic ring (preferably a carbon-nitrogen bond adjacent to an aromatic ring). In the present disclosure, a "carbon adjacent to an aromatic ring" refers to a carbon atom that is one atom (i.e., directly bonded to an atom constituting the aromatic ring), two atoms (i.e., there is one other atom between the carbon atom and the atom constituting the aromatic ring), or three atoms (i.e., there are two other atoms between the carbon atom and the atom constituting the aromatic ring) away from an atom constituting the aromatic ring (e.g., a carbon atom, a nitrogen atom, a sulfur atom, etc.). The carbon adjacent to the aromatic ring is preferably a carbon atom that is one or two atoms away from an atom constituting the aromatic ring, and more preferably a carbon atom that is one atom away from an atom constituting the aromatic ring (i.e., a carbon atom that is directly bonded to an atom constituting the aromatic ring).

[0044] According to a preferred embodiment of the present disclosure, the carbon-heteroatom bond is the bond between the benzyl group and the nitrogen atom.

[0045] According to one embodiment of the present disclosure, the substrate organic compound is a compound in which a benzyl group is coordinated to the nitrogen atom of an aniline structure. According to a preferred embodiment of the present disclosure, the substrate organic compound is N-benzyl-N-butyl-3-methylaniline.

[0046] [Method for Producing Hydrocracking Catalyst] According to another embodiment of the present disclosure, there is provided a method for producing a hydrogenolysis catalyst that hydrogenolyzes a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the method comprising: mixing a carbon-based support carrying a palladium catalyst with water; and mixing the resulting mixture with a phosphoric acid compound or an acetic acid compound.

[0047] (Step of mixing a carbon-based carrier carrying a palladium catalyst with water) According to one embodiment of the present disclosure, in the above production method, a step of mixing a carbon-based carrier carrying a palladium catalyst with water (also referred to as a "first mixing step" in the present disclosure) is carried out. In the first mixing step, the carbon-based carrier carrying a palladium catalyst and water may be mixed using, for example, a desired stirring device (e.g., a known stirring device) to obtain a mixture (also referred to as a "first mixture" in the present disclosure). The first mixture may be in the form of a slurry.

[0048] The carbon-based carrier carrying a palladium catalyst used in the first mixing step may be a carbon-based carrier carrying a palladium catalyst by a known method, or may be a commercially available palladium-supported carbon-based carrier.

[0049] In the first mixing step, the mixing ratio of the carbon-based carrier supporting the palladium catalyst and the water is not particularly limited, but may be, for example, 10 to 10,000 parts by mass, preferably 50 to 5,000 parts by mass, more preferably 200 to 3,000 parts by mass, and even more preferably 500 to 1,000 parts by mass of water per 100 parts by mass of the carbon-based carrier supporting the palladium catalyst (dry weight).

[0050] In the first mixing step, the mixing conditions (temperature, time, stirring speed, etc.) for mixing the carbon-based carrier carrying the palladium catalyst with water can be appropriately adjusted by a person skilled in the art.

[0051] In the first mixing step, other components may be mixed sequentially or simultaneously as needed, as long as the object of the present disclosure is not impaired.

[0052] (Step of mixing the obtained mixture with at least one of a phosphoric acid compound and an acetic acid compound) According to one embodiment of the present disclosure, the production method includes mixing the mixture obtained in the first mixing step (first mixture) with a phosphoric acid compound or an acetic acid compound (also referred to as a "second mixing step" in the present disclosure). In the second mixing step, the first mixture obtained in the first mixing step (i.e., a mixture containing a carbon-based carrier supporting a palladium catalyst and water) with at least one of a phosphoric acid compound and an acetic acid compound may be mixed using, for example, a desired stirring device (e.g., a known stirring device) to obtain a mixture (also referred to as a "second mixture" in the present disclosure).

[0053] In the second mixing step, the mixing ratio of the first mixture and at least one of the phosphoric acid compound and the acetic acid compound is not particularly limited, but may be, for example, 0.001 to 100 parts by mass, preferably 0.01 to 30 parts by mass, more preferably 0.1 to 10 parts by mass, and even more preferably 0.3 to 5 parts by mass of at least one of the phosphoric acid compound and the acetic acid compound per 100 parts by mass of the first mixture.

[0054] In the second mixing step, the mixing conditions (temperature, time, stirring speed, etc.) of the first mixture with at least one of the phosphoric acid compound and the acetic acid compound can be appropriately adjusted by a person skilled in the art.

[0055] In the second mixing step, other components may be mixed sequentially or simultaneously as needed, as long as the object of the present disclosure is not impaired.

[0056] (Filtration Step) According to one embodiment of the present disclosure, the method for producing a hydrocracking catalyst includes filtering the second mixture (also referred to as the "filtration step" in the present disclosure). Performing the filtration step is advantageous in that it allows impurities (e.g., at least one of unreacted phosphoric acid compounds and acetic acid compounds) and excess water to be removed from the hydrocracking catalyst.

[0057] In the filtration step, the second mixture (or the second mixture after further treatment) is filtered to obtain a filtrate, which contains at least the carbon-based support carrying the palladium catalyst and at least one of a phosphoric acid compound and an acetate compound.

[0058] In the filtration step, the filtration method may be, but is not limited to, filter filtration, centrifugal filtration, or the like.

[0059] In the filtration step, the filtration conditions (temperature, time, type of filter, etc.) can be adjusted as appropriate by those skilled in the art.

[0060] (Dehydration Step) According to one embodiment of the present disclosure, the second mixture (or a product of the second mixture further treated) or the filtrate is dehydrated (also referred to as the "dehydration step" in the present disclosure). By carrying out the dehydration step, the water content in the hydrocracking catalyst can be advantageously adjusted to a desired range.

[0061] In the dehydration step, the second mixture (or the second mixture after further treatment) or the filtrate may be dehydrated by a desired method (for example, drying, centrifugation, etc.).

[0062] In the dehydration step, the dehydration conditions (temperature, time, stirring speed, etc.) can be appropriately adjusted by a person skilled in the art.

[0063] The order of the filtration step and the dehydration step may be reversed as necessary.

[0064] In addition to the steps described above, other steps may be added to the method for producing a hydrocracking catalyst according to the present disclosure, as necessary.

[0065] [Uses of Hydrocracking Catalyst] The hydrocracking catalyst of the present disclosure can be used for the hydrocracking of a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond. The hydrocracking catalyst of the present disclosure can be used for the purpose of a deprotection reaction of a protecting group that protects a highly reactive site in a molecule from reacting with other sites. Therefore, according to one embodiment of the present disclosure, the hydrocracking catalyst of the present disclosure is used for the deprotection of the substrate compound.

[0066] According to another embodiment of the present disclosure, there is provided a method for hydrocracking the carbon-heteroatom bond, comprising contacting a substrate organic compound containing the carbon-heteroatom bond with molecular hydrogen and the hydrocracking catalyst described above.

[0067] (Contacting step of substrate organic compound, molecular hydrogen, and hydrocracking catalyst) According to one embodiment of the present disclosure, the hydrocracking method includes contacting the substrate organic compound containing the carbon-heteroatom bond with molecular hydrogen and the hydrocracking catalyst (also referred to as the "contacting step" in the present disclosure). In the contacting step, the substrate organic compound containing the carbon-heteroatom bond, molecular hydrogen, and the hydrocracking catalyst can be contacted in a desired reaction system (e.g., a reaction vessel) to carry out the hydrocracking reaction.

[0068] The ratio of the amount of the hydrocracking catalyst to the amount of the substrate organic compound used is not particularly limited as long as it is a ratio that allows the hydrocracking reaction to occur, but may be, for example, 0.001 to 100 parts by mass, preferably 0.01 to 50 parts by mass, more preferably 0.1 to 20 parts by mass, and even more preferably 1 to 10 parts by mass of the hydrocracking catalyst per 100 parts by mass of the substrate organic compound. Furthermore, the ratio of the amount of the hydrocracking catalyst to the amount of the substrate organic compound used may be, for example, 0.001 to 100 mol, preferably 0.01 to 10 mol, more preferably 0.05 to 5 mol, and even more preferably 0.1 to 3 mol of the hydrocracking catalyst per 1 mol of the substrate organic compound.

[0069] The molecular hydrogen may be present in the liquid phase or gas phase of the reaction system (e.g., in a reaction vessel). The pressure of the hydrogen supplied to the reaction system is not particularly limited as long as it is a pressure at which the hydrocracking reaction can proceed, and may be, for example, 0.01 to 1 MPa, preferably 0.05 to 0.8 MPa, and more preferably 0.1 to 0.6 MPa.

[0070] The hydrocracking reaction may be carried out in the presence of a desired reaction solvent. The reaction solvent may be one capable of dissolving at least a portion of the substrate organic compound and / or the hydrocracking catalyst. The reaction solvent is not particularly limited as long as it does not completely inhibit the hydrocracking reaction. Examples of the reaction solvent include ethers such as diethyl ether, t-butyl methyl ether, and tetrahydrofuran; alcohols such as 2-propanol, methanol, and ethanol; polar solvents such as N,N-dimethylformamide; esters such as ethyl acetate and propyl acetate; linear hydrocarbons such as n-hexane and n-heptane; and nonpolar solvents such as cyclic hydrocarbons such as cyclohexane. The hydrocracking catalyst and / or hydrocracking method of the present disclosure is advantageous in that it can be used in both polar and nonpolar solvents.

[0071] The amount of the reaction solvent is not particularly limited as long as it is an amount that allows the hydrogenolysis reaction to proceed. From the viewpoint of conducting a stable hydrogenolysis reaction, the amount may be, for example, 1 to 10,000 parts by mass, preferably 1 to 100 parts by mass, more preferably 10 to 50 parts by mass, and even more preferably 10 to 20 parts by mass, relative to 100 parts by mass of the substrate organic compound.

[0072] The reaction temperature when carrying out the hydrogenolysis reaction is not particularly limited as long as it is a temperature at which the hydrogenolysis reaction can proceed, and may be, for example, −30 to 80° C., preferably −15 to 60° C., more preferably 0 to 50° C., and even more preferably 10 to 30° C. A person skilled in the art can appropriately adjust the reaction temperature in consideration of the type of substrate organic compound used, the reaction time, etc.

[0073] The reaction time when carrying out the hydrogenolysis reaction is not particularly limited as long as it is a time period during which the hydrogenolysis reaction can proceed, and may be, for example, 0.1 to 48 hours, preferably 0.1 to 24 hours, and more preferably 0.1 to 10 hours. A person skilled in the art can appropriately adjust the reaction time by taking into consideration the type of substrate organic compound used, the reaction temperature, etc.

[0074] In the above-mentioned hydrogenolysis reaction, if bonds other than the target carbon-heteroatom bond (for example, bonds in an aromatic ring, other double bonds, triple bonds, etc. present in the substrate organic compound) are hydrogenated, the amount of the hydrogenolysis catalyst, the amount of molecular hydrogen, the hydrogen pressure, the reaction temperature, the reaction time, etc. may be appropriately adjusted, or the bonds other than the target carbon-heteroatom bond may be protected in advance with another protecting group (preferably a protecting group that is not decomposed in the hydrogenolysis reaction using the hydrogenolysis catalyst of the present disclosure), etc.

[0075] [Method for Producing Resulting Organic Compound] The above-mentioned hydrogenolysis reaction can produce a resultant organic compound in which at least one carbon-heteroatom bond of a substrate organic compound containing the carbon-heteroatom bond has been hydrogenolyzed. Therefore, according to another embodiment of the present disclosure, there is provided a method for producing a resultant organic compound in which at least one carbon-heteroatom bond has been hydrogenolyzed, the method comprising contacting (preferably reacting) the substrate organic compound containing the carbon-heteroatom bond with (preferably reacting) the molecular hydrogen and the hydrogenolysis catalyst, for example, in a reactor.

[0076] After the desired hydrogenolysis reaction is completed, the resulting organic compound may be isolated from the post-reaction solution containing the resulting organic compound by, for example, a known method. Therefore, according to one embodiment of the present disclosure, the production method may include isolating the resulting organic compound obtained in the reaction step. Isolation methods include, but are not limited to, separation, distillation, column chromatography, recrystallization, and the like.

[0077] The present disclosure includes the following: [1] A hydrogenolysis catalyst for hydrogenolysis of a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the hydrogenolysis catalyst comprising a carbon-based support on which at least a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound are supported. [2] The hydrogenolysis catalyst according to [1], which comprises a carbon-based support on which at least a phosphoric acid compound is supported. [3] The hydrogenolysis catalyst according to [1] or [2], wherein the phosphoric acid compound comprises at least one selected from the group consisting of phosphoric acid (orthophosphoric acid), pyrophosphoric acid, metaphosphoric acid, and diphosphoric acid pentoxide. [4] The hydrogenolysis catalyst according to any one of [1] to [3], wherein the phosphoric acid compound comprises at least phosphoric acid (orthophosphoric acid). [5] The hydrogenolysis catalyst according to [1], wherein the acetic acid compound comprises at least one selected from the group consisting of acetic acid, trifluoroacetic acid, monochloroacetic acid, dichloroacetic acid, and dimethylacetic acid. [6] The hydrocracking catalyst according to any one of [1] to [5], wherein the carbon-based support comprises at least one selected from the group consisting of activated carbon, mesoporous carbon, graphene, and carbon nanotubes. [7] The hydrocracking catalyst according to any one of [1] to [6], wherein, per 100 parts by mass of the hydrocracking catalyst (dry basis), the amount of the palladium catalyst is 1 to 20 parts by mass, the amount of the phosphorus compound or the acetate compound is 1 to 20 parts by mass, and the amount of the carbon-based support is 10 to 50 parts by mass. [8] The hydrocracking catalyst according to any one of [1] to [7], wherein, per 100 parts by mass of the hydrocracking catalyst (dry basis), the amount of water is 5 to 70 parts by mass. [9] The hydrocracking catalyst according to any one of [1] to [8], wherein, per 100 parts by mass of the hydrocracking catalyst (dry basis), the amount of phosphorus is 0.25 to 5 parts by mass.

[10] The hydrocracking catalyst according to any one of [1] to [9], wherein the carbon-heteroatom bond is a carbon-nitrogen bond.

[11] The hydrocracking catalyst according to

[10] , wherein the carbon-nitrogen bond is a bond between a carbon atom and a nitrogen atom adjacent to an aromatic ring.

[12] A method for producing a hydrogenolysis catalyst for hydrogenolysis of a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the method comprising: mixing a carbon-based support on which a palladium catalyst is supported with water, and mixing the resulting mixture with at least one of a phosphoric acid compound and an acetic acid compound.

[13] A method for producing a product organic compound in which at least one carbon-heteroatom bond has been hydrogenolyzed, the method comprising contacting a substrate organic compound containing a carbon-heteroatom bond with molecular hydrogen and a hydrogenolysis catalyst in a reactor, the hydrogenolysis catalyst comprising a carbon-based support on which a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound are supported.

[0078] The hydrocracking catalyst of the present disclosure will be described in more detail below using examples. However, the following examples are not intended to limit the hydrocracking catalyst of the present disclosure in any way. Unless otherwise specified, percentages and ratios described herein are by mass. Furthermore, unless otherwise specified, units and measurement methods described herein are in accordance with the provisions of the Japanese Industrial Standards (JIS).

[0079] Example 1: Phosphoric Acid-Supported 5% Pd / C Catalyst. 120 g of 5% Pd / C (manufactured by N.E. Chemcat Corporation, product name: Pd / C PE Type (Pd 5%) (H2O)) was mixed with 960 mL of purified water and stirred for 5 minutes to obtain a Pd / C aqueous solution. Next, the Pd / C aqueous solution was mixed with 10.3 mL of 85% aqueous phosphoric acid solution and stirred for 30 minutes. The mixture was then filtered and dehydrated to obtain the hydrocracking catalyst (phosphoric acid-supported 5% Pd / C catalyst) of Example 1. The 5% Pd / C used as the raw material was evaluated by elemental analysis. The amount of palladium in the carrier was 4.73%, and the amount of carbon-based carrier in the 5% Pd / C was estimated to be 95.27% (content on a dry basis). The water content of the resulting hydrocracking catalyst of Example 1 was 51.34%. Furthermore, the hydrocracking catalyst of Example 1 was evaluated by elemental analysis, and it was estimated that the phosphorus content in the carrier was 1.63% (content on a dry basis), and that 5.4 g of phosphoric acid was supported per 100 g of the hydrocracking catalyst (dry basis). Therefore, it was estimated that the hydrocracking catalyst of Example 1 contained approximately 5% palladium catalyst (elemental palladium) on a dry basis and approximately 44% carbon-based carrier on a dry basis.

[0080] Example 2: Phosphoric acid-supported 10% Pd / C catalyst 5.0 g of 10% Pd / C (manufactured by N.E. Chemcat Corporation, product name: P-10D (hydrated)) on a dry weight basis was mixed with 40 mL of pure water and stirred for 5 minutes to obtain a Pd / C aqueous solution. Next, the Pd / C aqueous solution was mixed with 0.43 mL of 85% phosphoric acid and stirred for 30 minutes, followed by filtration and dehydration to obtain the hydrocracking catalyst of Example 2 (phosphoric acid-supported 10% Pd / C catalyst). The water content of the obtained hydrocracking catalyst of Example 2 was 50%.

[0081] Example 3 Acetic Acid-Supported 10% Pd / C Catalyst 5.0 g of 10% Pd / C (manufactured by N.E. Chemcat Corporation, product name: P-10D (water-containing)) with a dry weight of 10% was mixed with 40 mL of pure water and stirred for 5 minutes to obtain an aqueous Pd / C solution. Next, the aqueous Pd / C solution was mixed with 0.43 mL of acetic acid and stirred for 30 minutes, followed by filtration and dehydration to obtain the hydrocracking catalyst of Example 3 (acetic acid-supported 10% Pd / C catalyst). The water content of the obtained hydrocracking catalyst of Example 3 was 50%.

[0082] Reference Example 1: 5% Pd / C catalyst 5% Pd / C (manufactured by N.E. Chemcat Corporation, trade name: Pd / C PE type (Pd 5%) (water-containing)) was used as the hydrocracking catalyst in Reference Example 1.

[0083] [Reference Examples 2 and 3: 10% Pd / C Catalyst] 10% Pd / C (manufactured by N.E. Chemcat Corporation, trade name: P-10D (hydrated)) was used as the hydrocracking catalyst in Reference Examples 2 and 3.

[0084] Reference Example 4: Mixture of 10% Pd / C catalyst and sulfo-group-imparted activated carbon 20 mg of 10% Pd / C (manufactured by N.E. Chemcat Corporation, trade name: P-10D (wet)) and sulfo-group-imparted activated carbon (manufactured by Futamura Chemical Co., Ltd., trade name: Taiko CP, catalog value: moisture 60 to 70%, particle size less than 0.18 mm, specific surface area 50 m) were mixed. ２ 30 mg of palladium (less than 1.0 mmol / g, sulfo group content 2.0 to 2.5 mmol / g) was mixed to obtain a hydrogenolysis catalyst of Reference Example 4. The Pd content in the obtained hydrogenation catalyst of Reference Example 4 was about 5% (content on a dry basis).

[0085] [Test Example 1: Hydrogenolysis reaction (debenzylation reaction) 1 / reaction in ethyl acetate] 0.8 mmol of the substrate organic compound, N-benzyl-N-butyl-3-methylaniline, and the hydrogenolysis catalyst of Example 1 or Reference Examples 1 to 4 were mixed in an ethyl acetate solvent, and the debenzylation reaction was carried out with stirring at room temperature (23°C) under a hydrogen pressure of 0.2 MPa for 1 hour. The resulting post-reaction solution was analyzed by gas chromatography (apparatus: GC-2010 manufactured by Shimadzu Corporation, column: DB-1 30.0 m, mobile phase: He), and the conversion rate was calculated from the amount of substrate organic compound lost. The results are shown in Table 1. Since only the peak for N-butyl-m-toluidine was observed in the resulting post-reaction solution, it was believed that a debenzylation reaction had occurred. In Table 1, the weight ratio of the substrate organic compound to Pd is expressed as the catalyst amount (wt%).

[0086]

[0087] [Test Example 2: Hydrogenolysis reaction (debenzylation reaction) 2 / reaction in cyclohexane] 0.8 mmol of N-benzyl-N-butyl-3-methylaniline, the substrate organic compound, and the hydrogenolysis catalyst obtained in Examples 2 and 3 or Reference Example 2 were mixed in a cyclohexane solvent, and the debenzylation reaction was carried out with stirring for 1 hour at room temperature (set at 23°C) under a hydrogen pressure of 0.2 MPa. The resulting post-reaction solution was analyzed by gas chromatography (under the same conditions as in Test Example 1), and the conversion rate was calculated from the amount of reduced substrate organic compound. The results are shown in Table 2. In Table 2, the weight ratio of the substrate organic compound to Pd is expressed as the catalyst amount (wt%).

[0088]

[0089] [Test Example 3: Hydrogenolysis reaction (debenzylation reaction) 3 / reaction in various solvents] 2.5 mmol of N-benzyl-N-butyl-3-methylaniline, the substrate organic compound, and the hydrogenolysis catalyst obtained in Example 1 were mixed in a solvent shown in Table 3, and the debenzylation reaction was carried out with stirring for 1 hour at room temperature (set at 23°C) under a hydrogen pressure of 0.2 MPa. The resulting post-reaction solution was analyzed by gas chromatography (under the same conditions as in Test Example 1), and the conversion rate was calculated from the amount of reduced substrate organic compound. The results are shown in Table 3. In Table 3, the weight ratio of the substrate organic compound to Pd is taken as the catalyst amount (wt%).

[0090]

[0091] [Test Examples 4 to 6: Hydrogenolysis reaction (debenzylation reaction) 4 / Reactions with various substrates] 2.5 mmol of the substrate organic compound shown in Table 4 and the hydrogenolysis catalyst obtained in Example 1 were mixed in a solvent shown in Table 4, and then a debenzylation reaction was carried out with stirring for 1 hour at room temperature (set at 23°C) under a hydrogen pressure of 0.2 MPa. The resulting post-reaction solution was analyzed by gas chromatography (under the same conditions as in Test Example 1), and the conversion rate was calculated from the amount of reduced substrate organic compound. The results are shown in Table 5. In Table 5, the weight ratio of the substrate organic compound to Pd is taken as the catalyst amount (wt%).

[0092]

[0093]

[0094] As is clear from the results of Test Example 1, the hydrocracking catalyst of the present disclosure exhibited superior catalytic activity in a polar solvent (e.g., ethyl acetate) compared to a conventional hydrocracking catalyst (e.g., Reference Example 1) supporting the same amount of palladium. Furthermore, the hydrocracking catalyst of the present disclosure exhibited catalytic activity equivalent to or superior to a conventional hydrocracking catalyst (e.g., Reference Example 2) supporting approximately twice the amount of palladium. Furthermore, the hydrocracking catalyst of the present disclosure exhibited catalytic activity equivalent to or superior to the hydrogenation catalyst of Reference Example 4 (corresponding to the hydrogenation catalyst described in Patent Document 2). The hydrocracking catalyst described in Patent Document 2 had manufacturability issues, such as the difference in deactivation times between the two types of catalysts and the need to deal with heat of dilution with water in the hydrous carbon and waste liquid treatment due to the use of a strong acid during production. In contrast, the hydrocracking catalyst of the present disclosure is advantageous in that it does not necessarily require two types of catalysts or a strong acid, and therefore does not require such issues. Furthermore, the hydrocracking catalyst of the present disclosure is particularly advantageous in that it does not necessarily require two types of catalysts, and does not necessarily require a strong acid, yet exhibits catalytic activity equivalent to or superior to that of the hydrogenation catalyst described in Patent Document 2.

[0095] As is clear from the results of Test Example 2, the hydrocracking catalyst of the present disclosure exhibited superior catalytic activity even in a non-polar solvent (e.g., cyclohexane) compared to a conventional hydrocracking catalyst carrying the same amount of palladium (e.g., Reference Example 2). Furthermore, as is clear from the results of Test Example 3, the hydrocracking catalyst of the present disclosure exhibited superior catalytic activity even when a wide range of solvents was used. Thus, the hydrocracking catalyst of the present disclosure is advantageous in that it can exhibit catalytic activity even in a wide range of solvents.

[0096] As is clear from the results of Test Examples 4 to 6, the hydrogenolysis catalyst of the present disclosure exhibited catalytic activity for a wide range of substrate organic compounds. In particular, Test Examples 4 and 6 suggest that the hydrogenolysis catalyst of the present disclosure is capable of not only debenzylation but also hydrogenolysis of double bonds (carbon-carbon double bonds) in side chains. Therefore, the hydrogenolysis catalyst of the present disclosure is advantageous in that it can hydrogenolysis not only carbon-heteroatom bonds but also carbon-carbon unsaturated bonds.

[0097] The hydrogenolysis catalyst of the present disclosure exhibits excellent hydrogenolysis reactions for carbon-heteroatom bonds. Without being bound by theory, it is believed that, for example, when N-benzyl-N-butyl-3-methylaniline is used as the substrate organic compound, a phosphoric acid compound or an acetic acid compound (preferably phosphoric acid or acetic acid) donates a proton to the nitrogen site coordinated with the benzyl group, and then a palladium catalyst contacts that site, resulting in hydrogenolysis (debenzylation). In particular, because the benzyl group can be destabilized by the proton donation reaction, hydrogenolysis by palladium can be carried out with less activation energy than conventional catalysts. As a result, it is believed that catalytic activity equivalent to or superior to that of conventional catalysts can be obtained even with a smaller amount of palladium compared to conventional catalysts. Previously, it was believed that the above reaction required the functional group to be imparted to a support due to the distance from the catalyst. However, surprisingly, it is believed that the above effect can also be achieved by supporting a phosphoric acid compound or an acetic acid compound (preferably phosphoric acid or acetic acid) on a support. Furthermore, it is known that aromatic rings such as those contained in benzyl groups can easily radicalize heteroatoms at the coordination site based on a resonance equation. Therefore, it is believed that an organic compound in which a protecting group containing an aromatic ring is coordinated to a heteroatom will undergo a particularly excellent hydrogenolysis reaction, regardless of the examples of the present disclosure.

Claims

1. A hydrogenolysis catalyst for hydrogenolysis of a carbon-heteroatom bond in a substrate organic compound, the hydrogenolysis catalyst comprising a carbon-based support carrying at least a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound.

2. The hydrocracking catalyst according to claim 1, wherein the phosphoric acid compound comprises at least one supported carbon-based support.

3. The hydrocracking catalyst according to claim 1, wherein the phosphoric acid compound comprises at least one selected from the group consisting of phosphoric acid (orthophosphoric acid), pyrophosphoric acid, metaphosphoric acid and diphosphoric acid pentoxide.

4. The hydrocracking catalyst according to claim 1, wherein the phosphoric acid compound comprises at least phosphoric acid (orthophosphoric acid).

5. The hydrocracking catalyst according to claim 1, wherein the acetic acid compound comprises at least one selected from the group consisting of acetic acid, trifluoroacetic acid, monochloroacetic acid, dichloroacetic acid and dimethylacetic acid.

6. The hydrocracking catalyst according to claim 1, wherein the carbon-based support comprises at least one selected from the group consisting of activated carbon, mesoporous carbon, graphene, and carbon nanotubes.

7. The hydrocracking catalyst according to claim 1, wherein, based on 100 parts by mass of the hydrocracking catalyst (dry basis), the amount of the palladium catalyst is 1 to 20 parts by mass, the amount of the phosphoric acid compound or the acetate compound is 1 to 20 parts by mass, and the amount of the carbon-based carrier is 10 to 50 parts by mass.

8. The hydrocracking catalyst according to claim 1, wherein the water content is 5 to 70 parts by mass per 100 parts by mass of the hydrocracking catalyst.

9. The hydrocracking catalyst according to claim 1, wherein the phosphorus element is 0.25 to 5 parts by mass per 100 parts by mass of the hydrocracking catalyst (dry basis).

10. The hydrocracking catalyst according to any one of claims 1 to 9, wherein the carbon-heteroatom bond is a carbon-nitrogen bond.

11. The hydrocracking catalyst according to claim 10, wherein the carbon-nitrogen bond is a bond between a carbon atom and a nitrogen atom adjacent to an aromatic ring.

12. A method for producing a hydrogenolysis catalyst for hydrogenolysis of a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the method comprising: mixing a carbon-based support carrying a palladium catalyst with water; and mixing the resulting mixture with at least one of a phosphoric acid compound and an acetic acid compound.

13. A method for producing a product organic compound in which at least one carbon-heteroatom bond has been hydrogenolyzed, comprising contacting a substrate organic compound containing a carbon-heteroatom bond with molecular hydrogen and a hydrogenolysis catalyst in a reactor, wherein the hydrogenolysis catalyst comprises a carbon-based support having supported thereon at least a palladium catalyst and at least one of a phosphoric acid compound and an acetic acid compound.

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