Hydrogenolysis catalyst and method for hydrogenolysis of carbon-heteroatom bonds and producing organic compounds

Abstract

Provided are: a hydrocracking catalyst capable of hydrocracking a carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond, the hydrocracking catalyst comprising at least a palladium catalyst and a carbon-based catalyst having a Bronsted acid site; and a method for producing an organic compound product by hydrocracking a carbon-heteroatom bond. The hydrocracking reaction catalyst is greatly reduced in the amount of palladium compared with the conventional palladium catalysts and has an equivalent or superior catalytic activity to those of the conventional catalysts, and it becomes possible to produce an organic material product continuously while preventing the deactivation of the palladium catalyst.

Description

[Technical Field]

[0001] The present invention relates to a hydrogenolysis catalyst and a method for producing a product organic compound by hydrogenolysis of a carbon-heteroatom bond using the hydrogenolysis catalyst. More specifically, the present invention relates to a hydrogenolysis catalyst capable of removing a protecting group having a carbon-heteroatom bond from a compound having the protecting group by hydrogenolysis, and a method for producing the product organic compound. [Background technology]

[0002] In the field of organic synthesis, the introduction and deprotection of various protecting groups is extremely important for synthesizing target compounds, and the carbon-heteroatom bond is known to be a structure that allows for easy introduction and deprotection of various protecting groups.

[0003] However, catalytic hydrogen reduction using a palladium / carbon catalyst is mainly used for the deprotection reaction of a protecting group once introduced (e.g., hydrogenolysis of a benzyl group, etc.). However, further improvements are being considered as the cost, yield, reaction rate, and durability of the catalyst are insufficient.

[0004] For example, Patent Document 1 discloses a debenzylation method characterized by reacting a palladium catalyst with hydrogen in the presence of an amine having one nitrogen atom, whereby the amine having one nitrogen atom modifies the palladium catalyst, and the modified palladium catalyst selectively hydrogenates the benzyl group that is a protecting group. Furthermore, Non-Patent Document 1 investigates a method for controlling the activity of a palladium catalyst by modifying the catalyst with a poisoning substance such as ethylenediamine.

[0005] Patent Document 2 also proposes a hydrocracking catalyst in which niobium oxide is further added to a catalyst supporting palladium particles. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 2017-197484 [Patent Document 2] International Publication No. 2018-225737 [Non-patent literature]

[0007] [Non-Patent Document 1] The Journal of Organic Chemistry, 1998, 63, 22,P7990-7992 Summary of the Invention [Problem to be solved by the invention]

[0008] However, the method of coating the surface of a palladium catalyst with an amine compound to adjust its activity, as described in Patent Document 1 and Non-Patent Document 1, contributes to improving the selectivity of the target product, but has problems in that the structure is optimized for the target product and therefore cannot be used for a wide range of compounds, and the reaction rate is insufficient due to reduced catalytic activity caused by poisoning. Furthermore, the hydrocracking catalyst described in Patent Document 2 has problems in that the high reactivity of niobium makes it difficult to manufacture the catalyst, and that niobium is difficult to obtain and costly, and that the palladium catalyst is quickly deactivated and has low durability.

[0009] In view of the above problems, an object of the present invention is to provide a hydrogenolysis catalyst that uses a significantly reduced amount of palladium compared to conventional palladium catalysts while maintaining catalytic activity equivalent to or superior to that of conventional catalysts, and a production method that suppresses deactivation of the palladium catalyst and enables continuous production of organic compounds. [Means for solving the problem]

[0010] As a result of extensive research, the present inventors have found that a hydrocracking catalyst comprising a palladium catalyst and a carbon-based catalyst containing Bronsted acid sites has catalytic activity superior to that of conventional palladium catalysts while reducing the amount of palladium used. Furthermore, the present inventors have discovered a method for continuously producing organic compounds in high yields while using a smaller amount of palladium than conventional methods.

[0011] That is, the present invention provides a hydrocracking catalyst for hydrocracking a carbon-heteroatom bond from a substrate organic compound containing the carbon-heteroatom bond, comprising: The hydrocracking catalyst includes at least a palladium catalyst and a carbon-based catalyst having Bronsted acid sites.

[0012] The present invention also provides a method for producing a product organic compound in which at least one carbon-heteroatom bond has been hydrogenolyzed, by contacting a substrate organic compound containing a carbon-heteroatom bond with molecular hydrogen, a Bronsted acid catalyst, and a palladium catalyst in a reactor. [Effects of the Invention]

[0013] The hydrocracking catalyst of the present invention has catalytic activity superior to that of conventional palladium catalysts while reducing the amount of palladium used.

[0014] Therefore, the hydrogenolysis catalyst of the present invention can continuously produce organic compounds at a high yield while using a smaller amount of palladium than conventional catalysts. DETAILED DESCRIPTION OF THE INVENTION

[0015] <Hydrocracking catalyst> The hydrocracking catalyst of the present invention comprises a palladium catalyst and a carbon-based catalyst having Brønsted acid sites. The palladium catalyst may be supported on a carbon-based catalyst having Brønsted acid sites, but is preferably a mixture of a palladium catalyst in which palladium is supported on a carbon material and a carbon-based catalyst having Brønsted acid sites. As described above, the use of a mixture can solve the production difficulty of further supporting palladium on a carbon-based catalyst with modified Brønsted acid sites, which results in the deactivation of the modified functional group due to reaction with the palladium complex. Furthermore, when the catalyst lifespans of the respective materials are different, a mixture is preferred because it allows for the preparation and replenishment of only the deactivated material.

[0016] <Palladium catalyst> In the hydrocracking catalyst of the present invention, the palladium catalyst is used as a hydrogenation catalyst. Known compounds such as particles and various alloys can be used as the palladium catalyst. Among these palladium catalysts, taking into consideration reactivity, selectivity, and the like, palladium catalysts in which palladium is supported on a carrier such as activated carbon, pulverized activated carbon, glassy carbon (GC), fine carbon, carbon black, graphite, carbon fiber, alumina, barium sulfate, silica, or calcium carbonate are preferred. Palladium catalysts in which palladium is supported on a carbon material such as activated carbon, pulverized activated carbon, glassy carbon (GC), fine carbon, carbon black, graphite, or carbon fiber are preferred. Palladium / carbon catalysts in which palladium is supported on activated carbon or glassy carbon are more preferred. The method for supporting palladium on a carrier is not particularly limited, and known methods can be used.

[0017] The specific surface area of ​​the support is usually 1 m 3 / g or more, preferably 10m 3 / g or more, more preferably 100m 3 / g or more, more preferably 300m 3 / g or more is preferred, while the upper limit is not particularly limited, but is preferably 3000m 3 / g or less, more preferably 2000m 3 / g or less, more preferably 1500m 3 / g or less, particularly preferably 1000m 3 / g or less.

[0018] When the total amount of palladium and the carrier is 100 parts by mass, the amount of supported palladium is usually 1 part by mass or more, preferably 3 parts by mass or more, more preferably 8 parts by mass or more, and even more preferably 10 parts by mass or less, while the upper limit is usually 50 parts by mass or less, preferably 40 parts by mass or less, more preferably 30 parts by mass or less, and even more preferably 20 parts by mass or less. By setting the amount within the above range, the contact area between palladium and the organic compound is ensured, and reactivity tends to be improved.

[0019] <Carbon-based catalyst with Bronsted acid sites> The carbon-based catalyst having a Brønsted acid site is not particularly limited as long as it is a carbon-based catalyst having a Brønsted acid site in its structure, but a carbon-based material that has been surface-treated with a Brønsted acid described below or that has a Brønsted acid described below supported thereon is preferred, and a carbon-based material that has been given a functional group that becomes a Brønsted acid site or that has a Brønsted acid supported thereon is more preferred. Examples of carbon-based materials include activated carbon, mesoporous carbon, graphene, carbon nanotubes, etc., and one or more of these can be used. Among these carbon-based materials, activated carbon is more preferred. Here, the Brønsted acid refers to a carbon-based material that has a proton (H + ) donor, and examples thereof include inorganic acids such as sulfuric acid, nitric acid, sulfonic acid, and trichloroacetic acid, with sulfuric acid, nitric acid, and sulfonic acid being preferred.

[0020] The surface functional groups that become Brønsted acid sites are not particularly limited as long as they function as Brønsted acid sites, but sulfo groups and carboxyl groups are preferred from the viewpoint of reactivity with organic compounds, with sulfo groups being particularly preferred. The sum of the amounts of the functional groups imparted to the surface of the carbon-based material is typically 0.1 mmol / g or more, preferably 0.3 mol / g or more, preferably 0.5 mmol / g or more, and more preferably 0.8 mmol / g or more, with the upper limit typically being 5.0 mmol / g or less, preferably 3.0 mmol / g or less, and more preferably 2.6 mmol / g or less. By being within the above range, sufficient catalytic activity can be obtained.

[0021] Known methods can be used to modify the surface of a carbon-based material with the functional groups to perform surface treatment. For example, when modifying a sulfo group, a method of contacting the carbon-based material with a sulfonating agent containing concentrated sulfuric acid, fuming sulfuric acid, sulfur trioxide, a sulfonic acid compound, or the like, followed by heating can be used. When modifying a carboxyl group, a method of contacting the carbon-based material with an inorganic acid such as nitric acid or a mixed acid of inorganic acids such as nitric acid and sulfuric acid, followed by heating can be used. Among these methods, those using a sulfonating agent or an inorganic acid are preferred, and those using a sulfonating agent or nitric acid are more preferred.

[0022] In the present invention, among carbon-based catalysts having Bronsted acid sites, it is preferable to use a carbon-based material whose surface is treated with an inorganic acid or a sulfonating agent. Examples of the carbon-based material include activated carbon, mesoporous carbon, graphene, and carbon nanotubes. These may be used in combination of two or more kinds.

[0023] Among carbon-based catalysts having Bronsted acid sites, the surface-treated activated carbon may be a commercially available product, such as the Taiko Solid Acid series (ZP, CP, PG, etc.) manufactured by Futamura Chemical Co., Ltd.

[0024] The hydrogenolysis catalyst of the present invention, with the above-described configuration, exhibits excellent effects in hydrogenolysis reactions of carbon-heteroatom bonds. While the reasons for these excellent effects in hydrogenolysis reactions are unclear, the following speculation is made. For example, when N-benzyl-N-butyl-3-methylaniline is used as a substrate organic compound, it is believed that the Bronsted acid site donates a proton to the nitrogen site coordinated with the benzyl group, and then the palladium catalyst contacts that site, resulting in hydrogenolysis (debenzylation). In particular, because the benzyl group is destabilized by the proton donation reaction, hydrogenolysis by palladium can be achieved with less activation energy than conventional methods. As a result, it is believed that excellent catalytic activity can be achieved even with a small amount of palladium. It is known that aromatic rings, such as those found in benzyl groups, readily radicalize the heteroatom at the coordination site based on resonance equations. Therefore, it is speculated that organic compounds in which a protecting group containing an aromatic ring is coordinated to a heteroatom exhibit particularly excellent hydrogenolysis reactions, regardless of the examples of the present invention.

[0025] [ka]

[0026] When the hydrocracking catalyst of the present invention is a mixture of a palladium catalyst and a carbonaceous material having Brønsted acid sites, the amount of the carbonaceous material having Brønsted acid sites is usually 1 part by mass or more, preferably 10 parts by mass or more, and more preferably 20 parts by mass or more per 100 parts by mass of the dry weight of the palladium catalyst, while the upper limit is usually 500 parts by mass or less, preferably 350 parts by mass or less, and more preferably 200 parts by mass or less. When the amount is within this range, the catalytic activity tends to be improved.

[0027] When the hydrocracking activity of the hydrocracking catalyst of the present invention decreases with use, the hydrocracking activity can be improved by treating it with the above-mentioned Brønsted acid or by adding a carbon-based catalyst having Brønsted acid sites to the reaction system.

[0028] <Substrate organic compounds containing carbon-heteroatom bonds> The hydrocracking catalyst of the present invention hydrocrackings the carbon-heteroatom bond in a substrate organic compound containing the carbon-heteroatom bond. Examples of heteroatoms in the substrate organic compound containing the carbon-heteroatom bond include nitrogen, oxygen, sulfur, and halogens such as chlorine, bromine, and iodine. From the viewpoint of facilitating the hydrocracking reaction, a nitrogen atom or an oxygen atom is preferred, and a nitrogen atom is more preferred.

[0029] The hydrogenolysis catalyst of the present invention is preferably used for the purpose of deprotection of a protecting group that protects a highly reactive site in a molecule from reaction with other sites, and therefore, the substrate organic compound is preferably a compound in which a protecting group is coordinated to the heteroatom site in the carbon-heteroatom bond. Specific protecting groups include aralkyl groups such as 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, and diphenylmethyl group; benzyloxycarbonyl group, 2-nitrobenzyloxycarbonyl group, 3-nitrobenzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, and 2-bromobenzyloxycarbonyl group. Examples of suitable protecting groups include aralkyloxycarbonyl groups such as aryloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 2-methoxybenzyloxycarbonyl, 3-methoxybenzyloxycarbonyl, and 4-methoxybenzyloxycarbonyl; alkyloxycarbonyl groups such as t-butyloxycarbonyl and t-amyloxycarbonyl; allyloxycarbonyl; and trialkylsilylcarbonyl groups such as trimethylsilyl and t-butyldimethylsilyl. Preferred protecting groups include benzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, and benzyloxycarbonyl, each having an aromatic ring structure, and more preferably benzyl. Among these substrate organic compounds, compounds in which a benzyl group is coordinated to the nitrogen atom of an aniline structure are more preferred, with N-benzyl-N-butyl-3-methylaniline being particularly preferred.

[0030] <Hydrogenolysis reaction and method for producing organic compounds using the reaction> The hydrogenolysis reaction in the present invention refers to a reaction in which a substrate organic compound containing a carbon-heteroatom bond is contacted with molecular hydrogen, a Bronsted acid catalyst, and a palladium catalyst in a reactor to cleave at least one carbon-heteroatom bond by hydrogenolysis. Because carbon-heteroatom bonds are generally susceptible to hydrogenolysis, the hydrogenolysis catalyst can cleave carbon-heteroatom bonds regardless of the structure of the organic compound. Examples of such reactions include deprotection reactions of benzyl protecting groups (Bz), tert-butoxycarbonyl protecting groups (Boc), benzyloxycarbonyl protecting groups (Cbz), and 9-fluorenylmethyloxycarbonyl protecting groups (Fmoc). Among these, the hydrogenolysis reaction is preferably used for debenzylation reactions, which are elimination reactions of benzyl protecting groups, and dehalogenation reactions.

[0031] Examples of the Bronsted acid catalyst include the Bronsted acid itself, a carbon-based catalyst having Bronsted acid sites, a zeolite having Bronsted acid sites, and a heteropolyacid. From the viewpoint of omitting catalyst separation from the reaction solution and a neutralization process, it is preferable to use a carbon-based catalyst having Bronsted acid sites. The amount of the Bronsted acid catalyst used in the hydrocracking reaction is not particularly limited, but the number of moles of the Bronsted acid catalyst relative to 1 mole of the substrate compound is preferably 0.001 to 100 moles, more preferably 0.01 to 10 moles, and even more preferably 0.05 to 5 moles.

[0032] The molecular hydrogen may be present in the liquid or gas phase in the reaction vessel. The pressure of the hydrogen supplied to the reaction vessel can be set arbitrarily, but is preferably 0.01 MPa or more and 1 MPa or less, and more preferably 0.05 MPa or more and 0.3 MPa or less.

[0033] In the above hydrogenolysis reaction, when aromatic rings other than the target carbon-heteroatom bond or double bonds are simultaneously hydrogenated, the selectivity of the produced organic compound tends to be improved by chemically modifying the palladium catalyst or by controlling reaction conditions such as the amount of hydrogen, reaction temperature, and reaction time.

[0034] The amount of the palladium catalyst used in the hydrogenolysis reaction is not particularly limited. However, in consideration of reaction selectivity, shortening of reaction time, yield, and ease of purification, the number of moles of palladium in the palladium catalyst relative to 1 mole of the substrate organic compound is preferably 0.001 to 100 moles, more preferably 0.01 to 10 moles, and even more preferably 0.05 to 5 moles.

[0035] In the present invention, when carrying out a hydrogenolysis reaction, a reaction solvent may be used to dissolve the substrate organic compound and the catalyst. The reaction solvent is preferably one that does not inhibit the hydrogenolysis reaction and that dissolves aromatic compounds. Examples of preferred reaction solvents include tetrahydrofuran, methanol, ethanol, propanol, ethyl acetate, hexane, heptane, toluene, and N,N-dimethylformamide.

[0036] When a reaction solvent is used, it is preferable to use 100 to 10,000 parts by mass of the reaction solvent per 100 parts by mass of the substrate organic compound in order to suppress a rapid reaction and carry out the hydrogenolysis reaction stably.

[0037] In the hydrogenolysis reaction of the present invention, the reaction temperature may be appropriately determined taking into consideration the solubility of the substrate organic compound, the melting point and boiling point of the reaction solvent, the reaction time, the reaction selectivity, etc. A lower reaction temperature generally improves the reaction selectivity but tends to lengthen the reaction time. On the other hand, a higher reaction temperature generally shortens the reaction time but tends to lower the reaction selectivity. Therefore, the reaction temperature is preferably −30° C. or higher and 50° C. or lower, more preferably −15° C. or higher and 40° C. or lower, and particularly preferably 10° C. or higher and 30° C. or lower.

[0038] In the hydrogenolysis reaction of the present invention, the reaction time can be appropriately determined by checking the conversion rate of the organic compound. However, under the above reaction conditions, the reaction time is preferably 0.1 to 48 hours, more preferably 0.1 to 24 hours, and particularly preferably 0.1 to 10 hours. Note that this reaction time refers to the time during which the organic compound is mixed with the palladium catalyst and the Bronsted acid catalyst in the presence of molecular hydrogen at the set reaction temperature.

[0039] Using the above-mentioned hydrogenolysis reaction, a substrate organic compound having a carbon-heteroatom bond can be contacted with a Brønsted acid catalyst, a palladium catalyst, and molecular hydrogen in a reactor to produce a product organic compound in which at least one carbon-heteroatom bond has been hydrogenolyzed. The method for contacting these components is not particularly limited, and examples include a method in which the substrate organic compound, palladium catalyst, Brønsted acid catalyst, and optionally a reaction solvent are all charged into a reactor, and then the atmosphere in the reactor is replaced with hydrogen gas and the mixture is stirred and mixed. The reactor used in these processes may be a batch reactor or a continuous reactor.

[0040] After the reaction is complete, the reaction solution containing the produced organic compound can be extracted by a known method to isolate the target compound, such as by separation, distillation, column chromatography, or recrystallization.

[0041] <Method for continuous production of organic compounds> After the first hydrogenolysis reaction is completed in the reactor, new substrate organic compounds and a Brønsted acid catalyst can be added to the reactor and re-contacted with the palladium catalyst used in the reaction. This allows for continuous production of the resulting organic compounds. Adding only the Brønsted acid catalyst again improves the activity of the palladium catalyst compared to when it is not added. This is presumably because the Brønsted acid catalyst readily reacts with the protecting group-derived compounds released by the hydrogenolysis of the carbon-heteroatom bond, and is therefore easily deactivated. Therefore, by replenishing the deactivated Brønsted acid catalyst together with the substrate organic compound, the protecting group-derived compounds preferentially react with the Brønsted acid catalyst, suppressing degradation of the palladium catalyst and preserving its ability to donate protons to the heteroatoms, thereby preserving its hydrogenolysis activity.

[0042] The amount of Bronsted acid catalyst added after the first hydrocracking reaction is completed in the reactor and before the next reaction is usually 1 part by mass or more, preferably 10 parts by mass or more, more preferably 20 parts by mass or more, relative to 100 parts by mass of the palladium catalyst in the reactor, with the upper limit usually being 500 parts by mass or less, preferably 300 parts by mass or less, more preferably 200 parts by mass or less. By having the amount in this range, the catalytic activity of the hydrocracking reaction is improved, and the life of the palladium catalyst tends to be improved as the Bronsted acid catalyst removes components that poison the palladium catalyst.

[0043] In the above-mentioned method for continuously producing the produced organic compound, it is preferable to use a carbon-based catalyst having the above-mentioned Bronsted acid sites as the Bronsted acid catalyst, from the viewpoint of being able to omit the process of separating the catalyst from the reaction solution and the neutralization process. [Example]

[0044] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0045] (Production Example 1: Method for producing activated carbon treated with nitric acid) Powdered activated carbon (product name: Shirasagi P9) manufactured by Osaka Gas Chemicals Co., Ltd. was immersed in a nitric acid aqueous solution (concentration: 0.5 mol / L) and stirred at room temperature for 10 minutes. After that, suction filtration was performed to obtain nitric acid-treated activated carbon (hereinafter sometimes referred to as HN / C) with a moisture content of 55%.

[0046] (Production Example 2: Method for producing activated carbon treated with sulfuric acid) Powdered activated carbon (product name: Shirasagi P9) manufactured by Osaka Gas Chemicals Co., Ltd. was immersed in a sulfuric acid solution (concentration: 0.5 mol / L) and stirred at room temperature for 10 minutes. After that, suction filtration was performed to obtain sulfuric acid-treated activated carbon (hereinafter sometimes referred to as HS / C) with a moisture content of 56%.

[0047] (Production Example 3: Method for producing hydrocracking catalyst) 30 mg (dry weight) of the HN / C produced in Production Example 1 and 20 mg of 10% Pd / C catalyst (water content 60%, Pd = 0.008 mmol) manufactured by N.E. Chemcat Corporation were mixed in a container to obtain a hydrogenolysis catalyst (mixture).

[0048] (Example 1 Hydrogenolysis Reaction (Debenzylation Reaction)) 0.8 mmol of the substrate organic compound, N-benzyl-N-butyl-3-methylaniline, and the hydrogenolysis catalyst obtained in Production Example 3 were mixed in a toluene solvent, and the debenzylation reaction was carried out with stirring at room temperature (set at 23°C) under a hydrogen pressure of 0.1 MPa for 1 hour. The resulting post-reaction solution was analyzed by gas chromatography, and the conversion rate was determined from the amount of substrate organic compound lost. The results are shown in Table 1. Furthermore, since only the peak for N-butyl-m-toluidine was observed in the resulting post-reaction solution, it can be inferred that the debenzylation reaction had occurred. The post-reaction solution was then withdrawn, and toluene was passed through the reactor. After that, new substrate organic compound and solvent were added without changing the hydrogenolysis catalyst, and the debenzylation reaction was carried out in the same manner as above. The results are shown in Table 1. In Table 1, the weight of 10% Pd / C, which gave a molar ratio of substrate organic compound to Pd of 100:1 (corresponding to Comparative Example 1), was taken as 100.

[0049] The debenzylation reaction in this example is as follows. [ka]

[0050] Example 2 The reaction was carried out and evaluated in the same manner as in Example 1, except that the hydrogenolysis catalyst was changed to a mixture of 30 mg of HS / C and 20 mg of 10% Pd / C catalyst instead of the mixture in Production Example 3. The results are shown in Table 1.

[0051] Example 3 A hydrogenolysis catalyst was prepared from the mixture of Production Example 3 using sulfo-functionalized activated carbon (product name: Taiko CP, catalog value: moisture 60%-70%, particle size less than 0.18 mm, specific surface area 50 m) manufactured by Futamura Chemical Co., Ltd. 2 The reaction was carried out and evaluated in the same manner as in Example 1, except that a mixture of 30 mg of a 10% Pd / C catalyst (sulfo group content: less than 2.0 mmol / g, sulfo group content: 2.0 to 2.5 mmol / g) and 20 mg of a 10% Pd / C catalyst was used. The results are shown in Table 1.

[0052] Example 4 A hydrogenolysis catalyst was prepared from the mixture of Production Example 3 using sulfo-functionalized activated carbon (product name: Taiko ZP, catalog values: moisture 60%-70%, particle size less than 0.18 mm, specific surface area 500-1000 m) manufactured by Futamura Chemical Co., Ltd. 2 The reaction was carried out and evaluated in the same manner as in Example 1, except that a mixture of 30 mg of 1.0 to 1.3 mmol / g sulfo group (1.0 to 1.3 mmol / g) and 20 mg of 10% Pd / C catalyst was used. The results are shown in Table 1.

[0053] Example 5 A hydrocracking catalyst was prepared from the mixture of Production Example 3 using sulfo-functionalized activated carbon manufactured by Futamura Chemical Co., Ltd. (product name: Taiko CP (high temperature grade), catalog values: moisture 60%-70%, particle size less than 0.18 mm, specific surface area 50 m 2 The reaction was carried out and evaluated in the same manner as in Example 1, except that a mixture of 30 mg of a 10% Pd / C catalyst (sulfo group content: less than 2.0 mmol / g, sulfo group content: 2.0 to 2.5 mmol / g) and 20 mg of a 10% Pd / C catalyst was used. The results are shown in Table 1.

[0054] Example 6 A hydrocracking catalyst was prepared from the mixture of Production Example 3 using sulfo-functionalized activated carbon manufactured by Futamura Chemical Co., Ltd. (product name: Taiko ZP (high-temperature grade), catalog values: moisture 60%-70%, particle size less than 0.18 mm, specific surface area 500-1000 m). 2 The reaction was carried out and evaluated in the same manner as in Example 1, except that a mixture of 30 mg of 1.0 to 1.3 mmol / g sulfo group (1.0 to 1.3 mmol / g) and 20 mg of 10% Pd / C catalyst was used. The results are shown in Table 1.

[0055] (Comparative Example 1) The reaction was carried out and evaluated in the same manner as in Example 1, except that the hydrogenolysis catalyst was changed from the mixture of Production Example 3 to 20 mg of 10% Pd / C catalyst manufactured by N.E. Chemcat Corporation. The results are shown in Table 1.

[0056] [Table 1]

[0057] It can be seen that a higher conversion rate can be obtained with a hydrocracking catalyst that is a mixture of a palladium catalyst and a carbon-based catalyst having Bronsted acid sites, as described in Examples 1 to 6, than with a hydrocracking catalyst containing only a palladium catalyst, as described in Comparative Example 1.

[0058] (Examples 7 to 14) In the debenzylation reaction, the hydrogenolysis catalyst had the composition shown in Table 2, and the reaction was carried out once in the same manner as in Example 1, and evaluation was performed. The results are shown in Table 2.

[0059] [Table 2]

[0060] It was found from Examples 1, 7 to 9 and Examples 2 to 6, and 10 to 14 that when the palladium catalyst was taken as 100 parts by mass, even when the mixed amount of the carbon-based catalyst having Bronsted acid sites was anywhere from 30 to 150 parts by mass, a conversion rate superior to that of Comparative Example 1 was obtained. Furthermore, it was found from Example 9 that even when the amount of the palladium catalyst was half that of Comparative Example 1, the conversion rate was improved by using the palladium catalyst in combination with the carbon-based catalyst having Bronsted acid sites.

[0061] Example 2-1 The same hydrocracking reaction as in Example 1 was carried out using the same catalyst composition as in Example 7 (10% Pd / C 100 parts by mass, HN / C 150 parts by mass). Next, a reaction solution was obtained while leaving the hydrocracking catalyst in the reactor. Analysis of the remaining amount of substrate compound contained in the obtained reaction solution revealed a conversion rate of 97%.

[0062] (Example 2-2) After the reaction in Example 2-1, the vessel was washed with toluene, and the 10% Pd / C and HN / C mixture recovered by filtration was returned to the vessel. A toluene solution containing 0.8 mmol of the substrate organic compound and 150 parts by mass of the HN / C catalyst was added, and a second reaction was carried out under the same conditions. As a result, the conversion rate was 95%.

[0063] (Example 2-3) After the reaction in Example 2-2, the vessel was washed with toluene, and the 10% Pd / C and HN / C mixture recovered by filtration was returned to the vessel. A toluene solution containing 0.8 mmol of the substrate organic compound and 150 parts by mass of HN / C catalyst was added, and the reaction was repeated a third time under the same conditions. As a result, the conversion rate was 98%.

[0064] (Comparative Example 2-1) After the reaction in Example 2-3, the vessel was washed with toluene, and the mixture of 10% Pd / C and HN / C recovered by filtration was returned to the vessel. A toluene solution containing 0.8 mmol of the substrate organic compound was added, and the fourth reaction was carried out under the same conditions as the previous one, except that no HN / C was added. As a result, the conversion rate was 29%.

[0065] (Examples 2-4) After the reaction in Comparative Example 2-1, the vessel was washed with toluene, and the 10% Pd / C and HN / C mixture recovered by filtration was returned to the vessel. A toluene solution containing 0.8 mmol of the substrate organic compound and 150 parts by mass of the HN / C catalyst was added, and the fifth reaction was carried out under the same conditions. As a result, the conversion rate was 99%.

[0066] From Examples 2-1 to 2-4, it was found that, in line with the hypothesis that a large amount of Brønsted acid is deactivated with each reaction, resulting in a decrease in conversion, multiple reactions can be carried out at a high conversion without adding a palladium catalyst by replenishing only the carbon-based catalyst having Brønsted acid sites that is consumed with each reaction. Furthermore, from Comparative Example 2-1, in which no carbon-based catalyst having Brønsted acid sites was added, it became clear that the maintenance of the above conversion rate was due to the additional effect of the carbon-based catalyst having Brønsted acid sites. [Industrial Applicability]

[0067] The present invention can hydrogenolyze a carbon-heteroatom bond from a substrate organic compound containing the carbon-heteroatom bond, and therefore can be used in deprotection reactions in the synthesis of organic compounds used in various pharmaceuticals, agricultural chemicals, etc.

Claims

1. A hydrocracking catalyst for hydrocracking a carbon-nitrogen bond from a substrate organic compound containing the carbon-nitrogen bond, comprising: The hydrocracking catalyst is a mixture of a palladium catalyst in which palladium is supported on a carbon material and a carbon-based catalyst having Bronsted acid sites.

2. The hydrocracking catalyst according to claim 1, wherein the carbon-based catalyst having Bronsted acid sites is a carbon-based material whose surface has been treated with an inorganic acid or a sulfonating agent.

3. The hydrocracking catalyst according to claim 2, wherein the carbon-based material is one or more selected from the group consisting of activated carbon, mesoporous carbon, graphene, and carbon nanotubes.

4. For 100 parts by mass of palladium catalyst, 4. The hydrocracking catalyst according to claim 1, wherein the catalyst contains 1 part by mass or more and 500 parts by mass or less of a carbon-based catalyst having Bronsted acid sites.

5. 5. The hydrocracking catalyst according to claim 1, wherein the carbon-based catalyst having Bronsted acid sites is a carbon-based material modified with sulfo groups in an amount of 0.1 mmol / g or more and 5.0 mmol / g or less, or a carbon-based material treated with nitric acid.

6. The hydrocracking catalyst according to claim 1, wherein the carbon-based catalyst having Bronsted acid sites does not contain palladium.

7. The hydrocracking catalyst according to claim 6, wherein the palladium catalyst in which palladium is supported on a carbon material does not contain any Bronsted acid sites.

8. The method comprises contacting a mixture of a substrate organic compound containing a carbon-nitrogen bond, molecular hydrogen, a carbon-based catalyst having a Bronsted acid site, and a palladium catalyst in which palladium is supported on a carbon material in a reactor, to produce a product organic compound in which at least one carbon-nitrogen bond has been hydrogenolyzed.

9. A method for continuously producing a product organic compound, comprising the steps of: after producing a product organic compound in which the carbon-nitrogen bond has been hydrogenolyzed by the method according to claim 8, adding fresh substrate organic compound and a carbon-based catalyst having a Bronsted acid site into the reactor; and bringing the palladium used in the reaction into contact again with the palladium catalyst supported on a carbon material.

10. 10. The method for continuously producing a product organic compound according to claim 9, wherein the amount of the carbon-based catalyst having Bronsted acid sites to be added is 1 part by mass or more and 500 parts by mass or less per 100 parts by mass of the palladium catalyst in which palladium is supported on a carbon material in the reactor.

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