Device for producing cyclic amine and method for producing cyclic amine

Abstract

Provided are a device for producing a cyclic amine and a method for producing a cyclic amine with which it is possible to produce a cyclic amine by hydrogenation of a nitrogen-containing heteroaromatic compound under normal temperature and normal pressure without using hydrogen gas. The device for producing a cyclic amine is provided with a substrate supply unit that supplies a nitrogen-containing heteroaromatic compound, which is the substrate, and an anion exchange membrane electrolysis unit that electrolytically hydrogenates the substrate supplied from the substrate supply unit to produce the cyclic amine.

Description

Apparatus for producing cyclic amines and method for producing cyclic amines

[0001] The present invention relates to an apparatus for producing a cyclic amine and a method for producing a cyclic amine.

[0002] Cyclic amines are important skeletons contained in the majority of small molecule drugs approved by the FDA (Food and Drug Administration), and various cyclic amines have been produced to date.

[0003] Piperidine, the most representative cyclic amine, requires high-energy conditions (high temperature and high pressure conditions) industrially and is synthesized by chemical hydrogenation of pyridine using hydrogen gas as the hydrogen source (Non-Patent Document 1).

[0004] Eller, Karsten et al., “Amines, Aliphatic”. Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002 / 14356007.a02_001.

[0005] Conventionally, the production of cyclic amines such as piperidine has been achieved by chemical hydrogenation of nitrogen-containing heteroaromatic compounds, which requires high temperatures and pressures and consumes a lot of energy. Furthermore, hydrogen gas is used as a raw material for the hydrogenation.

[0006] As described above, conventionally, the production of cyclic amines has required high-energy conditions such as high temperature and high pressure, as well as hydrogen gas as a raw material.

[0007] In order to solve these problems, an object of the present invention is to provide an apparatus for producing a cyclic amine, which is capable of producing a cyclic amine by hydrogenating a nitrogen-containing heteroaromatic compound at room temperature and atmospheric pressure without using hydrogen gas, and a method for producing a cyclic amine.

[0008] The above-mentioned problems are solved by the present invention, which is specified as follows: (1) An apparatus for producing a cyclic amine, comprising: a substrate supply unit that supplies a nitrogen-containing heteroaromatic compound as a substrate; and an anion exchange membrane electrolysis unit that produces a cyclic amine by electrolytic hydrogenation of the substrate supplied from the substrate supply unit. (2) The apparatus for producing a cyclic amine according to (1), wherein the anion exchange membrane electrolysis unit has a cathode including a cathode catalyst layer, an anode including a metal oxide, and an anion exchange membrane provided between the cathode and the anode, and the substrate supply unit supplies the substrate to the cathode. (3) The apparatus for producing a cyclic amine according to (2), wherein the cathode catalyst layer contains at least one catalytic metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. (4) A method for producing a cyclic amine, comprising supplying a nitrogen-containing heteroaromatic compound as a substrate to an anion exchange membrane electrolysis unit, and the anion exchange membrane electrolysis unit electrolytically hydrogenating the supplied substrate to produce a cyclic amine. (5) The method for producing a cyclic amine according to (4), wherein the anion exchange membrane electrolysis unit comprises a cathode including a cathode catalyst layer, an anode including a metal oxide, and an anion exchange membrane provided between the cathode and the anode, and the substrate is supplied to the cathode. (6) The method for producing a cyclic amine according to (5), wherein the cathode catalyst layer comprises at least one catalytic metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh.

[0009] According to the present invention, it is possible to provide an apparatus for producing a cyclic amine and a method for producing a cyclic amine, which are capable of producing a cyclic amine by hydrogenating a nitrogen-containing heteroaromatic compound at room temperature and atmospheric pressure without using hydrogen gas.

[0010] Fig. 1 is a schematic diagram of a cyclic amine production apparatus 10 according to Embodiment 1 of the present invention. Fig. 2 is a schematic exploded view of an anion exchange membrane electrolysis unit 12 according to Embodiments 1 and 2 of the present invention. Fig. 3 is a schematic diagram of a cyclic amine production apparatus 20 according to Embodiment 2 of the present invention.

[0011] Next, embodiments of the present invention will be described in detail with reference to the drawings. It should be understood that the present invention is not limited to the following embodiments, and that appropriate design changes and improvements may be made based on the ordinary knowledge of those skilled in the art without departing from the spirit of the present invention.

[0012] 1 shows a schematic diagram of a cyclic amine production apparatus 10 according to Embodiment 1 of the present invention. The cyclic amine production apparatus 10 includes an anion exchange membrane electrolysis unit 12, a substrate supply unit 11, an electrolyte solution supply unit 21, and pipes 22, 23, 24, and 25.

[0013] Figure 2 shows a schematic exploded view of the anion exchange membrane electrolysis unit 12 according to Embodiment 1 of the present invention. The anion exchange membrane electrolysis unit 12 has an anion exchange membrane (AEM) 13, and a cathode 14a, a gasket 14b, a separator 15, and an end plate 16 are stacked in this order from one side of the anion exchange membrane 13. Furthermore, an anode 17a, a gasket 17b, a separator 18, and an end plate 19 are stacked in this order from the other side of the anion exchange membrane 13. The anion exchange membrane electrolysis unit 12 is a stack of multiple components obtained in this way, and the multiple components are fixed to each other by being evenly fastened with bolts or the like at multiple locations.

[0014] There are no particular limitations on the size of the above-described components constituting the anion exchange membrane electrolysis unit 12, and the components can be formed to a desired size as necessary. As one example, of the above-described components constituting the anion exchange membrane electrolysis unit 12, the cathode 14a and the anode 17a can be plate-shaped members having dimensions of length × width × thickness = 1 to 5 cm × 3 to 10 cm × 50 to 1000 μm, and the rest can be plate-shaped members having dimensions of length × width × thickness = 5 to 20 cm × 5 to 20 cm × 0.01 to 2 cm.

[0015] There are no particular limitations on the anion exchange membrane 13, and any known anion exchange membrane can be used. The anion exchange membrane 13 is positively charged due to positive charge exchange groups fixed to the membrane, and prevents the passage of cations while allowing only anions to pass through.

[0016] The cathode 14a is embedded approximately in the center of the thin-plate-shaped gasket 14b. The cathode 14a has a substrate and a cathode catalyst layer formed on the substrate's surface. The substrate can be made of porous nickel, porous titanium, woven carbon fabric (carbon cloth), nonwoven carbon fabric, carbon paper, or the like. Carbon cloth is a woven fabric made by bundling hundreds of thin carbon fibers with diameters of several micrometers. Carbon paper is made by sintering a thin film precursor made of carbon raw fiber through a papermaking process. The substrate of the cathode 14a may have a water-repellent surface, but it is more preferable to use a substrate without a water-repellent surface. The shape of the cathode catalyst layer is not particularly limited, but a porous carbon material carrying a catalytic metal can be used. Examples of the porous carbon material for the cathode catalyst layer include electron-conductive materials containing, as a main component, porous carbon, porous metal, or porous metal oxide. Examples of porous carbon include carbon blacks such as Ketjen Black (registered trademark), acetylene black, furnace black, and Vulcan (registered trademark). Examples of porous metals include Pt black, Pd black, and fractally precipitated Pt metal. Examples of porous metal oxides include oxides of Ti, Zr, Nb, Mo, Hf, Ta, and W. Furthermore, porous metal compounds such as nitrides, carbides, oxynitrides, carbonitrides, and partially oxidized carbonitrides of metals such as Ti, Zr, Nb, Mo, Hf, Ta, and W can also be used as catalyst supports. Examples of catalytic metals for the cathode catalytic layer include at least one catalytic metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. The amount of catalytic metal supported on the porous carbon material can be appropriately designed in consideration of the efficiency with which the substrate nitrogen-containing heteroaromatic compound is hydrogenated and the cost, and may be, for example, about 10 to 50 mass %.

[0017] The method for producing the cathode 14a is not particularly limited. For example, first, a porous carbon material carrying a catalytic metal is mixed with a solution prepared by dispersing an ionomer in a solvent such as water or alcohol to obtain a catalyst slurry. The ionomer coats the catalyst support carrying the catalytic metal. This improves the ionic conductivity of the cathode 14a. Examples of anion-conducting ionomers include polymers having strong basic groups (quaternary ammonium groups, imidazolium groups, etc.).

[0018] Next, the catalyst slurry is applied to the surface of a substrate such as carbon paper, dried, and then the catalyst slurry is applied again and dried repeatedly to form a cathode catalyst layer on the surface of the substrate, thereby producing the cathode 14a.

[0019] The gasket 14b is provided to prevent leakage of the solution containing the substrate supplied to the cathode 14a from the substrate supply unit 11 described below. The material of the gasket 14b is not particularly limited as long as it does not react with the cathode 14a and the substrate, and for example, a gasket made of a fluorine-based elastomer such as Teflon (registered trademark) or Viton (registered trademark) can be used.

[0020] The anode 17a is embedded approximately in the center of the gasket 17b, which is formed in a thin plate shape. The shape of the anode 17a is not particularly limited, but a metal substrate with a metal oxide attached to the surface can be used. The metal substrate can be, for example, a mesh substrate, metal fiber, a sintered porous metal, a foam molded body, or an expanded metal, and can be made of a metal with excellent corrosion resistance, such as Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, Nb, Mo, Ta, or W. The metal oxide of the anode 17a can be at least one catalyst selected from the group consisting of iridium oxide, ruthenium oxide, and tantalum oxide.

[0021] The gasket 17b is provided to prevent leakage of water or an aqueous solution supplied to the anode 17a from an electrolyte supply unit 21 (described later). The material of the gasket 17b is not particularly limited as long as it does not react with the anode 17a, and for example, a fluorine-based elastomer such as Teflon (registered trademark) or Viton (registered trademark) can be used.

[0022] Both separators 15 and 18 constitute current collectors. Separators 15 and 18 can be made of a carbon resin or a corrosion-resistant alloy such as a Cr-Ni-Fe system, a Cr-Ni-Mo-Fe system, a Cr-Mo-Nb-Ni system, a Cr-Mo-Fe-W-Ni system, or a Ti system.

[0023] The end plates 16, 19 are each made of a conductive material. Each of the end plates 16, 19 is preferably a member strong enough to protect the anion exchange membrane electrolysis unit 12, and may be made of stainless steel or gold-plated stainless steel. The end plate 16 is electrically connected to the negative terminal of an external power supply, and the end plate 19 is electrically connected to the positive terminal of the external power supply.

[0024] The substrate supply unit 11 accommodates a nitrogen-containing heteroaromatic compound as a substrate and supplies it to the anion exchange membrane electrolysis unit 12. The nitrogen-containing heteroaromatic compound may be accommodated in the substrate supply unit 11 in a state of being dissolved in an organic solvent, or if the nitrogen-containing heteroaromatic compound is liquid at room temperature, it may be accommodated in the substrate supply unit 11 as is. The organic solvent is not particularly limited, but is preferably one that does not corrode the anion exchange membrane, and examples of the organic solvent include methyl tertiary butyl ether, diisopropyl ether, tetrahydrofuran, and 2-methyltetrahydrofuran. When the nitrogen-containing heteroaromatic compound is dissolved in an organic solvent, the concentration of the nitrogen-containing heteroaromatic compound is not particularly limited, but can be 1 to 1000 mM.

[0025] A pipe 22, which serves as a supply path for the nitrogen-containing heteroaromatic compound to the anion exchange membrane electrolysis unit 12, is connected to the substrate supply unit 11. The pipe 22 is provided so as to penetrate the end plate 16 and the separator 15, and the nitrogen-containing heteroaromatic compound that has passed through the pipe 22 is supplied to the cathode 14a. The nitrogen-containing heteroaromatic compound can be supplied using a known pump or the like.

[0026] Meanwhile, the pipe 23 is provided to extend from the cathode 14a through the separator 15 and the end plate 16, and a solution containing a cyclic amine produced by electrolytic hydrogenation of the substrate at the cathode 14a is discharged from the anion exchange membrane electrolysis unit 12. The pipe 23 may also be connected to the substrate supply unit 11 so as to return the solution containing the cyclic amine to the substrate supply unit 11. With this configuration, the solution containing the cyclic amine produced at the cathode 14a can be circulated between the substrate supply unit 11 and the anion exchange membrane electrolysis unit 12. Therefore, even if the solution containing the cyclic amine produced at the cathode 14a contains unreacted nitrogen-containing heteroaromatic compounds, it can be repeatedly fed to the cathode 14a, allowing the cyclic amine to be efficiently and completely reacted to form a cyclic amine.

[0027] The electrolyte solution supply unit 21 stores water, preferably pure water, or a basic aqueous solution and supplies it to the anion exchange membrane electrolysis unit 12. The basic aqueous solution is not particularly limited as long as it supplies hydroxide ions by electrolysis, and examples include an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, and an aqueous ammonia solution. The concentration of the basic aqueous solution is also not particularly limited, but can be 10 to 1000 mM.

[0028] A pipe 25, which serves as a supply path for water or a basic aqueous solution to the anion exchange membrane electrolysis unit 12, is connected to the electrolyte solution supply unit 21. The pipe 25 is provided so as to penetrate the end plate 19 and the separator 18, and the water or basic aqueous solution that has passed through the pipe 25 is supplied to the anode 17a. The water or basic aqueous solution can be supplied using a known pump or the like.

[0029] Meanwhile, the pipe 24 is provided to penetrate from the anode 17a through the separator 18 and the end plate 19, and the dissolved oxygen solution produced at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12. The pipe 24 may also be connected to the electrolyte solution supply unit 21 so as to return the dissolved oxygen solution to the electrolyte solution supply unit 21. Such a configuration enables the reaction system to be designed compactly.

[0030] <Method for Producing Cyclic Amine> Next, a method for producing a cyclic amine according to embodiment 1 of the present invention will be described. First, a cyclic amine production apparatus 10 having the configuration shown in Figures 1 and 2 is prepared. A nitrogen-containing heteroaromatic compound as a substrate is placed in the substrate supply unit 11, and water or a basic aqueous solution is placed in the electrolyte supply unit 21.

[0031] Next, the nitrogen-containing heteroaromatic compound as the substrate is supplied from the substrate supply unit 11 at room temperature and atmospheric pressure through the pipe 22 to the cathode 14a of the anion exchange membrane electrolysis unit 12. Meanwhile, water or a basic aqueous solution is supplied from the electrolyte solution supply unit 21 at room temperature and atmospheric pressure through the pipe 25 to the anode 17a of the anion exchange membrane electrolysis unit 12. External power supplies are electrically connected to the end plates 16 and 19 of the anion exchange membrane electrolysis unit 12, and an electrolysis reaction occurs at the cathode 14a and the anode 17a due to current from the external power supply.

[0032] In the electrolysis reaction at the cathode 14a, a portion or all of the unsaturated bonds in the aromatic ring of the nitrogen-containing heteroaromatic compound are electrolytically hydrogenated to produce a cyclic amine. The hydrogen source for this electrolytic hydrogenation is activated hydrogen species generated on the catalytic metal of the cathode 14a by water electrolysis, while in the electrolysis reaction at the anode 17a, electrons are released from hydroxide ions in the electrolyte to produce oxygen and water. The electrolysis reactions at the cathode 14a and anode 17a are shown in Equations (1) and (2), respectively. In Equations (1) and (2), n represents a natural number. At this time, the anion exchange membrane 13 allows hydroxide ions to pass from the cathode 14a side to the anode 17a side and water to pass from the anode 17a side to the cathode 14a side.

[0033]

[0034] The cyclic amine production apparatus 10 according to the first embodiment of the present invention converts a nitrogen-containing heteroaromatic compound into a cyclic amine by electrolytic hydrogenation, but the types of the nitrogen-containing heteroaromatic compound and the cyclic amine product are not particularly limited. Examples of cyclic amines produced by the cyclic amine production apparatus 10 according to the first embodiment of the present invention include monocyclic or polycyclic cyclic amine compounds having one or more nitrogen atoms in a five- or six-membered ring and having an aliphatic or partially unsaturated bond. Specific examples of the nitrogen-containing heteroaromatic compound and cyclic amine are shown in formulas (3) to (17). The left sides of the formulas (3) to (17) each represent an example of the nitrogen-containing heteroaromatic compound ((3) pyridines, (4) quinolines, (5) isoquinolines, (6) pyrazines, (7) pyrroles, (8) indoles, (9) imidazoles, (10) indolizines, (11) 2-methylpyridine, (12) 3-methylpyridine, (13) 4-methylpyridine, (14) 2-ethylpyridine, (15) 2,6-dimethylpyridine, (16) 3-pyridinecarboxamide, and (17) 4-phenylpyridine). The right-hand sides of the formulas (3) to (17) each represent an example of a cyclic amine obtained by electrolytic hydrogenation of the corresponding nitrogen-containing heteroaromatic compound ((3) piperidines, (4) 1,2,3,4-tetrahydroquinolines, (5) 1,2,3,4-tetrahydroisoquinolines, (6) piperazines, (7) pyrrolidines, (8) indolines, (9) imidazolidines, (10) 5,6,7,8-tetrahydroindolizines, (11) 2-methylpiperidine, (12) 3-methylpiperidine, (13) 4-methylpiperidine, (14) 2-ethylpiperidine, (15) 2,6-dimethylpiperidine, (16) 3-piperidinecarboxamide, and (17) 4-phenylpiperidine).

[0035]

[0036]

[0037] In addition to the compounds described above, cyclic amines produced by the cyclic amine production apparatus 10 according to the first embodiment of the present invention can also be produced by electrolytic hydrogenation of part or all of the unsaturated bonds in the aromatic ring of a nitrogen-containing heteroaromatic compound. For example, cyclic amines such as 1,4-dihydropyridine, acridan, and 5,6-dihydrophenanthridine can also be produced.

[0038] A solution containing a cyclic amine produced by electrolytic hydrogenation of a substrate at the cathode 14a of the cyclic amine production apparatus 10 is discharged from the anion exchange membrane electrolysis unit 12 through a pipe 23. Meanwhile, a solution containing oxygen produced at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12 through a pipe 24. When the pipe 23 is connected to the substrate supply unit 11, the solution containing the cyclic amine produced at the cathode 14a circulates between the substrate supply unit 11 and the anion exchange membrane electrolysis unit 12. By circulating in this manner, even if the solution containing the cyclic amine produced at the cathode 14a contains unreacted nitrogen-containing heteroaromatic compounds, it can be repeatedly fed to the cathode 14a, enabling the cyclic amine to be efficiently and completely reacted to form a cyclic amine.

[0039] Embodiment 2 <Configuration of Cyclic Amine Production Apparatus> Figure 3 shows a schematic diagram of a cyclic amine production apparatus 20 according to Embodiment 2 of the present invention. The cyclic amine production apparatus 20 includes an anion exchange membrane electrolysis unit 12, a substrate and electrolyte supply unit 26, and pipes 22, 23, and 24. Unlike the cyclic amine production apparatus 10 according to Embodiment 1, the cyclic amine production apparatus 20 simultaneously supplies the substrate and the electrolyte to the cathode 14a.

[0040] The anion exchange membrane electrolysis unit 12 used in the cyclic amine production apparatus 20 according to the second embodiment of the present invention has a similar configuration to the anion exchange membrane electrolysis unit 12 of the cyclic amine production apparatus 10 described in the first embodiment.

[0041] The substrate and electrolyte supply unit 26 accommodates a nitrogen-containing heteroaromatic compound as a substrate and supplies it to the anion exchange membrane electrolysis unit 12. The nitrogen-containing heteroaromatic compound may be accommodated in the substrate and electrolyte supply unit 26 in a state of being dissolved in an organic solvent, or if the nitrogen-containing heteroaromatic compound is liquid at room temperature, it may be accommodated in the substrate and electrolyte supply unit 26 as is. The organic solvent is not particularly limited, but is preferably one that does not corrode the anion exchange membrane and is miscible with water, such as tetrahydrofuran or 2-methyltetrahydrofuran. When the nitrogen-containing heteroaromatic compound is dissolved in an organic solvent, the concentration of the nitrogen-containing heteroaromatic compound is not particularly limited, but can be 1 to 1000 mM.

[0042] The substrate and electrolyte supply unit 26 is connected to a pipe 22 that serves as a supply path for the nitrogen-containing heteroaromatic compound and the electrolyte to the anion exchange membrane electrolysis unit 12. The pipe 22 is provided so as to penetrate the end plate 16 and the separator 15, and the nitrogen-containing heteroaromatic compound and the electrolyte that have passed through the pipe 22 are supplied to the cathode 14a. The nitrogen-containing heteroaromatic compound and the electrolyte can be supplied using a known pump or the like.

[0043] Meanwhile, the pipe 23 is provided to extend from the cathode 14a through the separator 15 and the end plate 16, and a solution containing a cyclic amine produced by electrolytic hydrogenation of the substrate at the cathode 14a is discharged from the anion exchange membrane electrolysis unit 12. The pipe 23 may also be connected to the substrate and electrolyte solution supply unit 26 so that the solution containing the cyclic amine is returned to the substrate and electrolyte solution supply unit 26. With this configuration, the solution containing the cyclic amine produced at the cathode 14a can be circulated between the substrate and electrolyte solution supply unit 26 and the anion exchange membrane electrolysis unit 12. Therefore, even if the solution containing the cyclic amine produced at the cathode 14a contains unreacted nitrogen-containing heteroaromatic compounds, it can be repeatedly fed to the cathode 14a, allowing the cyclic amine to be efficiently and completely reacted to form a cyclic amine.

[0044] In addition to the nitrogen-containing heteroaromatic compound, the substrate and electrolyte supply unit 26 also contains water, preferably pure water, or a basic aqueous solution, and supplies it to the anion exchange membrane electrolysis unit 12. The basic aqueous solution is not particularly limited as long as it supplies hydroxide ions by electrolysis, and examples include an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, and an aqueous ammonia solution. The concentration of the basic aqueous solution is also not particularly limited, but can be 10 to 1000 mM.

[0045] A pipe 24 is provided on the anode 17a side of the cyclic amine production apparatus 20 so as to penetrate from the anode 17a through the separator 18 and the end plate 19, and oxygen generated at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12.

[0046] <Method for Producing Cyclic Amine> Next, a method for producing a cyclic amine according to embodiment 2 of the present invention will be described. First, a cyclic amine production apparatus 20 having the configuration shown in Figures 2 and 3 is prepared. A substrate and electrolyte supply unit 26 is charged with a nitrogen-containing heteroaromatic compound as a substrate, and water or a basic aqueous solution.

[0047] Next, a nitrogen-containing heteroaromatic compound as the substrate and water or a basic aqueous solution are simultaneously supplied at room temperature and pressure from the substrate and electrolyte solution supply unit 26 through the pipe 22 to the cathode 14a of the anion exchange membrane electrolysis unit 12. External power supplies are electrically connected to the end plates 16 and 19 of the anion exchange membrane electrolysis unit 12, and an electrolysis reaction occurs at the cathode 14a and the anode 17a due to current from the external power supplies.

[0048] In the electrolysis reaction at the cathode 14a, a portion or all of the unsaturated bonds in the aromatic ring of the nitrogen-containing heteroaromatic compound are electrolytically hydrogenated to produce a cyclic amine. The hydrogen source for this electrolytic hydrogenation is activated hydrogen species generated on the catalytic metal of the cathode 14a by water electrolysis, while in the electrolysis reaction at the anode 17a, electrons are released from hydroxide ions in the electrolyte to produce oxygen and water. The electrolysis reactions at the cathode 14a and anode 17a are shown in formulas (1') and (2'), respectively. In formulas (1') and (2'), n represents a natural number. At this time, the anion exchange membrane 13 allows hydroxide ions to pass from the cathode 14a side to the anode 17a side, and allows water to pass from the anode 17a side to the cathode 14a side. The H generated in the electrolysis reaction at the anode 17a ２ O is discharged from the pipe 24 as water vapor or water droplets.

[0049]

[0050] The cyclic amine production apparatus 20 according to the second embodiment of the present invention converts a nitrogen-containing heteroaromatic compound into a cyclic amine by electrolytic hydrogenation. The types of the nitrogen-containing heteroaromatic compound and the cyclic amine product are not particularly limited, and examples thereof include the cyclic amines shown in the first embodiment.

[0051] A solution containing a cyclic amine produced by electrolytic hydrogenation of a substrate at the cathode 14a of the cyclic amine production apparatus 20 is discharged from the anion exchange membrane electrolysis unit 12 through a pipe 23. Meanwhile, oxygen produced at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12 through a pipe 24. When the pipe 23 is connected to the substrate and electrolyte solution supply unit 26, the solution containing the cyclic amine produced at the cathode 14a circulates between the substrate and electrolyte solution supply unit 26 and the anion exchange membrane electrolysis unit 12. By circulating in this manner, even if the solution containing the cyclic amine produced at the cathode 14a contains unreacted nitrogen-containing heteroaromatic compounds, it can be repeatedly fed to the cathode 14a, enabling the cyclic amine to be efficiently and completely reacted to form a cyclic amine.

[0052] In the cyclic amine production apparatus 20 according to embodiment 2 of the present invention, the substrate and electrolyte supply units are combined into a single "substrate and electrolyte supply unit 26." This allows the production apparatus to be more compact than the cyclic amine production apparatus 10 according to embodiment 1, and simplifies the production process. Furthermore, even when using relatively inexpensive metals such as Co, Ni, and Fe as well as expensive noble metals (Pt, Pd, and Rh) as the cathode catalyst layer, cyclic amines can be obtained with a low amount of electricity and in good yield. Furthermore, there have been no previous reports, including non-electrolytic systems, of the hydrogenation of pyridines at room temperature and atmospheric pressure using the inexpensive metal Co. In this respect, too, the cyclic amine production apparatus 20 according to embodiment 2 of the present invention provides an extremely excellent reaction system.

[0053] <Effects of the Cyclic Amine Production Apparatus and Cyclic Amine Production Method> Conventionally, the production of cyclic amines such as piperidine has involved the use of energy-intensive chemical hydrogenation processes of nitrogen-containing heteroaromatic compounds, such as those involving high temperatures and high pressures. Furthermore, hydrogen gas has been used as a raw material for hydrogenation. In contrast, the cyclic amine production apparatuses 10 and 20 and cyclic amine production methods according to embodiments 1 and 2 of the present invention achieve the production of cyclic amines by electrochemical hydrogenation of nitrogen-containing heteroaromatic compounds at room temperature and atmospheric pressure. Furthermore, the cyclic amine production apparatuses 10 and 20 and cyclic amine production methods according to embodiments 1 and 2 of the present invention use activated hydrogen species generated on a catalytic metal by water electrolysis as the hydrogen source for hydrogenation, eliminating the need for hydrogen gas.

[0054] Furthermore, the desired electrolytic hydrogenation proceeds smoothly by using the anion exchange membrane electrolysis unit 12 in the cyclic amine production apparatus 10, 20. Note that when a general-purpose proton exchange membrane electrolysis unit is used as the same solid polymer electrolysis unit, a neutralized salt is formed in the proton exchange membrane because both the substrate and the product are basic substances, and the reaction does not proceed.

[0055] While many chemical and pharmaceutical manufacturers are pushing ahead with the "electrification" of organic reactions in order to achieve carbon neutrality, the electrolytic synthesis of cyclic amines remains an unexplored technology, and this invention is the first to successfully develop this technology.

[0056] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0057] Example 1 1. Preparation of an Anion Exchange Membrane Electrolysis Unit An anion exchange membrane electrolysis unit having the configuration shown in FIG. 2 was prepared as follows. In Example 1, Rh supported on Ketjen Black (KB, registered trademark) (Rh / KB) was used as the cathode catalyst layer. First, a slurry (slurry concentration 7% by mass) was prepared as follows. That is, Rh / KB (manufactured by Tanaka Kikinzoku Kogyo K.K., Rh supported amount: 28.9% by mass), in which rhodium was supported as a catalytic metal on porous carbon as a catalyst support, was weighed out. Next, pure water, an anion ionomer solution (AS-4, manufactured by Tokuyama Corporation, 2 to 10% by mass 1-propanol solution), and 1-propanol were added to an 80 mL Teflon (registered trademark) container together with Rh / KB to prepare a dispersion. The amount of anion ionomer added was set so that the weight ratio of the carbon (ionomer / carbon) supporting the carbon-supported metal catalyst was 0.8, assuming a 5% by mass anion ionomer solution. Furthermore, the pure water and 1-propanol were set so that the weight ratio of the solvent contained in the resulting slurry was pure water:1-propanol = 1:99. Ten 2.5 mm diameter zirconia balls were placed in a Teflon (registered trademark) container and mixed for 20 minutes at 200 rpm using a pot mill to obtain a catalyst slurry. The slurry was applied to a 1 cm x 4 cm carbon paper (SGL35BC, manufactured by SGL Carbon) and dried in an oven at 40°C for approximately 10 minutes to volatilize the solvent. After drying, the weight of the carbon paper was measured, and additional slurry was applied as necessary. This process was repeated until the metal loading reached 0.5 mg / cm. 2A cathode was fabricated so that the thickness of the cathode was 1 / 3. Nickel foam was used as the fabricated cathode and anode, and an anion exchange membrane was sandwiched between them to fabricate a membrane electrode assembly (MEA). Finally, stainless steel end plates on the cathode and anode sides, a carbon separator on the cathode side, a titanium separator on the anode side, Teflon (registered trademark) gaskets on the cathode and anode sides, and the MEA described above were assembled as shown in Figure 2 and tightened with bolts to fabricate an anion exchange membrane electrolysis unit. A torque wrench was used for tightening, and eight locations were tightened evenly with a force of 3.0 Nm. The dimensions (length x width x thickness) of each member are shown below. Each end plate: 10.5 cm x 12.5 cm x 1.2 cm Each separator: 6.5 cm x 8.5 cm x 1.3 cm Each gasket: 6.5 cm x 8.5 cm x 0.16 cm Cathode: 1.0 cm x 4.0 cm x 240 μm Anode: 1.0 cm x 4.0 cm x 120 μm Anion exchange membrane: 2 cm x 15 cm x 28 μm

[0058] 2. Electrolysis Using the anion exchange membrane electrolysis unit prepared as described above, a cyclic amine production apparatus having the configuration shown in FIG. 1 was prepared as follows, and electrolysis was performed. Specifically, a 10 mM potassium hydroxide aqueous solution was placed in the anode-side electrolyte supply section and supplied to the anode at a flow rate of 2.0 mL / min using a Microceramic Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). This solution was circulated between the anode and the electrolyte supply section. Meanwhile, a solution of 50 mM pyridine (3 mL) dissolved in methyl tertiary butyl ether was supplied to the cathode at a flow rate of 2.0 mL / min using a Microceramic Pump or a Smoothflow Pump. This solution was circulated between the cathode and the substrate supply section. Under this condition, a current of 50 mA / cm was applied. 2 (The geometric area of ​​the electrode is 4 cm 2Therefore, in this experiment, electrolysis was performed up to 30 F / mol at a current of 200 mA (1 F / mol current application took approximately 1 minute, and 30 F / mol current application took approximately 36 minutes). The electrolyte on both the cathode and anode sides during electrolysis was at room temperature, and the electrolysis was performed under normal pressure. The electrolyte after the reaction was analyzed by gas chromatography (absolute calibration method) to calculate the yield of the target cyclic amine (piperidine).

[0059] Example 2 An anion exchange membrane electrolysis unit was prepared in the same manner as in Example 1, except that Ru instead of Rh was used as the catalytic metal in the cathode catalyst layer and the amount of Ru supported on KB was 27.0 mass%, and electrolysis was performed, and the yield of the target cyclic amine (piperidine) was calculated.

[0060] Example 3 An anion exchange membrane electrolysis unit was prepared in the same manner as in Example 1, except that Pd instead of Rh was used as the catalytic metal in the cathode catalyst layer and the amount of Pd supported on the KB was 29.3 mass%, and electrolysis was performed, and the yield of the target cyclic amine (piperidine) was calculated.

[0061] Example 4 An anion exchange membrane electrolysis unit was prepared in the same manner as in Example 1, except that Pt instead of Rh was used as the catalytic metal in the cathode catalyst layer and the amount of Pt supported on the KB was 46.4 mass%, and electrolysis was performed, and the yield of the target cyclic amine (piperidine) was calculated.

[0062] Example 5 An anion exchange membrane electrolysis unit was prepared in the same manner as in Example 1, except that Co was used instead of Rh as the catalytic metal in the cathode catalyst layer and the amount of Pt supported on the KB was 20.3 mass%, and electrolysis was performed to calculate the yield of the target cyclic amine. The yields of the cyclic amine (piperidine) obtained in Examples 1 to 5 are shown in Table 1.

[0063]

[0064] Example 6 An anion exchange membrane electrolysis unit was prepared in the same manner as in Example 1, except that a DSE (registered trademark) oxygen evolution electrode (manufactured by De Nora Permelec, Inc.) was used as the anode instead of nickel foam. Electrolysis was performed, and the yield of the target cyclic amine was calculated. Subsequently, a solution of 50 mM pyridine (3 mL) dissolved in methyl tertiary butyl ether was again supplied to the cathode substrate supply section at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation), and electrolysis was performed in the same manner. This electrolysis was repeated a total of six times, and the yield of the target cyclic amine was calculated for each. The yield of the cyclic amine (piperidine) obtained in Example 6 is shown in Table 2. Table 2 demonstrates that the yield of the cyclic amine does not decrease even with repeated use of the anion exchange membrane electrolysis unit.

[0065]

[0066] Example 7 Using the anion exchange membrane electrolysis unit prepared as described above, a cyclic amine production apparatus having the configuration shown in FIG. 1 was prepared as follows, and electrolysis was performed. Specifically, a 10 mM potassium hydroxide aqueous solution was placed in the anode-side electrolyte supply section and supplied to the anode at a flow rate of 2.0 mL / min using a Microceramic Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). This solution was circulated between the anode and the electrolyte supply section. Meanwhile, a solution of 50 mM quinoline (3 mL) dissolved in diisopropyl ether was supplied to the cathode at a flow rate of 2.0 mL / min using a Microceramic Pump or a Smoothflow Pump. This solution was circulated between the cathode and the substrate supply section. Under this condition, a current of 25 mA / cm was applied. 2 (The geometric area of ​​the electrode is 4 cm 2Therefore, in this experiment, electrolysis was performed at a current of 100 mA (1 F / mol for approximately 2 minutes and 30 seconds, and 20 F / mol for approximately 50 minutes) to 12, 16, and 20 F / mol. The electrolyte on both the cathode and anode sides of the electrolysis was at room temperature, and the electrolysis was performed under normal pressure. The electrolyte after the reaction was analyzed by gas chromatography (absolute calibration method) to calculate the yield of the target cyclic amine. The yield of the cyclic amine (1,2,3,4-tetrahydroquinoline) obtained in Example 7 was 91%.

[0067] Example 8 1. Preparation of an anion exchange membrane electrolysis unit Cathode catalyst layer: Rh (Rh / KB) with a Rh loading of 0.5 mg / cm ２ An anion exchange membrane electrolysis unit was produced in the same manner as in Example 1, except that:

[0068] 2. Electrolysis Using the anion exchange membrane electrolysis unit prepared as described above, a cyclic amine production apparatus having the configuration shown in Figure 3 was prepared as follows, and electrolysis was performed. The substrates used were pyridine, which is the substrate on the left side of the following formula (3'), and the substrates on the left sides of the above formulas (11) to (17) ((11) 2-methylpyridine, (12) 3-methylpyridine, (13) 4-methylpyridine, (14) 2-ethylpyridine, (15) 2,6-dimethylpyridine, (16) 3-pyridinecarboxamide, and (17) 4-phenylpyridine).

[0069]

[0070] First, a solution of 100 mM substrate (5 mL) dissolved in a solvent was placed in the substrate and electrolyte supply section on the cathode side and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (Yamazen Corporation) or a Smoothflow Pump (Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. Water was used as the solvent for the reactions of the above formulas (3') and (11) to (16), and a mixed solvent of water:tetrahydrofuran = 1:1 (volume ratio) was used for the reaction of the above formula (17) to improve the solubility of the substrate and product. Under this condition, a current of 50 mA / cm was applied.2 Electrolysis was carried out up to a predetermined current flow rate. The current flow time and current flow rate are shown in Table 3. Tests were carried out on the electrolyte solutions used in the electrolysis under normal pressure and at room temperature (25°C). The electrolyte solutions after the reaction were analyzed by gas chromatography (absolute calibration curve method) to calculate the yields of the target products, piperidine, which is the cyclic amine on the right side of the above formula (3'), and the cyclic amines on the right sides of (11) to (17) ((11) 2-methylpiperidine, (12) 3-methylpiperidine, (13) 4-methylpiperidine, (14) 2-ethylpiperidine, (15) 2,6-dimethylpiperidine, (16) 3-piperidinecarboxamide, and (17) 4-phenylpiperidine). The results are shown in Table 3 below.

[0071]

[0072] Example 9 Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3 , which had the same configuration as in Example 8. That is, a solution of 100 mM substrate (5 mL) dissolved in a mixed solvent of water:tetrahydrofuran = 1:1 (volume ratio) was placed in the substrate and electrolyte supply section on the cathode side, and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. 4-phenylpyridine, which is the substrate on the left side of the above formula (17), was used as the substrate. In this state, a current of 50 mA / cm was applied. 2 Electrolysis was carried out at a temperature of 14.9 F / mol. The current was passed for 1 hour. Tests were carried out on the electrolyte solution used in the electrolysis at room temperature (25°C), 40°C, and 50°C under normal pressure. The electrolyte solution after the reaction was analyzed by gas chromatography (absolute calibration curve method) to calculate the yield of the target cyclic amine (4-phenylpiperidine), and the results were as shown in Table 4 below.

[0073]

[0074] As shown in Table 4, when 4-phenylpyridine was used as the substrate and Rh supported on Ketjen Black (KB, registered trademark) (Rh / KB) was used as the cathode catalyst layer, the yield of cyclic amines tended to improve as the reaction temperature increased.

[0075] Example 10 Co supported on Ketjen Black (KB, registered trademark) (Co / KB, Co supported amount: 0.35 mg / cm ２ Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3 , which had the same configuration as in Example 8, except that a cyclic amine was used as the cathode catalyst layer. That is, a solution of 100 mM pyridine (5 mL) dissolved in water was placed in the substrate and electrolyte supply section on the cathode side, and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. In this state, a current of 20 mA / cm was applied. 2 Electrolysis was performed at 18 F / mol with a current of 1000 kJ / s. The current flow time was 3 hours. The electrolysis solution was tested at room temperature (25°C) under atmospheric pressure. The yield of the target cyclic amine (piperidine), calculated by gas chromatography (absolute calibration curve method) of the electrolytic solution after the reaction, was 90%. This yield is significantly improved compared to the 61% yield of cyclic amine (piperidine) in Example 5, which used the cyclic amine production apparatus configured as shown in Figure 1 and Co / KB as the cathode catalyst layer.

[0076] Example 11 Co supported on Ketjen Black (KB, registered trademark) (Co / KB, Co supported amount: 0.5 mg / cm ２Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3 , which had the same configuration as in Example 8, except that a cyclic amine was used as the cathode catalyst layer. Specifically, a solution of 100 mM pyridine (5 mL) dissolved in water was placed in the substrate and electrolyte supply section on the cathode side, and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. Under this condition, a current of 25 mA / cm was applied. 2 Electrolysis was performed at 1000 kJ / mol up to 6 F / mol. The current flow time was 1 hour. The electrolysis solution was tested at room temperature (25°C), 40°C, and 60°C under normal pressure. The electrolytic solution after the reaction was analyzed by gas chromatography (absolute calibration curve method) to calculate the yield of the target cyclic amine (piperidine), and the results were as shown in Table 5 below.

[0077]

[0078] As shown in Table 5, when pyridine was used as the substrate and Co supported on Ketjen Black (KB, registered trademark) (Co / KB) was used as the cathode catalyst layer, the yield of cyclic amines tended to improve as the reaction temperature decreased.

[0079] Example 12 Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3 , which had the same configuration as in Example 11 (cathode catalyst layer: Co / KB) except for the amount of Co supported in the cathode catalyst layer. That is, a solution of 100 mM pyridine (5 mL) dissolved in water was placed in the substrate and electrolyte supply section on the cathode side, and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. The amount of Co supported in the cathode catalyst layer was 0.2 mg / cm. ２ , 0.35mg / cm ２ , 0.5 mg / cm ２ , 1 mg / cm ２ In this state, 25 mA / cm2 Electrolysis was performed at 6 F / mol. The current flow time was 1 hour. The electrolysis solution was tested at room temperature (25°C) under normal pressure. The electrolysis solution after the reaction was analyzed by gas chromatography (absolute calibration curve method) to calculate the yield of the target cyclic amine (piperidine), and the results were as shown in Table 6 below.

[0080]

[0081] As shown in Table 6, when pyridine was used as the substrate and Co supported on Ketjen Black (KB, registered trademark) (Co / KB) was used as the cathode catalyst layer, the Co loading in the cathode catalyst layer was 0.35 mg / cm ２ It was found that the yield of the cyclic amine was the best when

[0082] Example 13 Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3 , which had the same configuration as in Example 11 (cathode catalyst layer: Co / KB) except for the cathode substrate. That is, a solution of 100 mM pyridine (5 mL) dissolved in water was placed in the substrate and electrolyte supply section on the cathode side, and supplied to the cathode at a flow rate of 2.0 mL / min using a Microceram Pump (manufactured by Yamazen Corporation) or a Smoothflow Pump (manufactured by Takumina Corporation). The solution was circulated between the cathode and the substrate and electrolyte supply section. In this state, a current of 25 mA / cm was applied. 2 Electrolysis was performed up to 6 F / mol. The current flow time was 1 hour. The electrolyte used in the electrolysis was tested at normal pressure and room temperature (25 ° C). As the cathode substrate, one using a gas diffusion layer Sigracet (registered trademark) GDL39BB (with a water-repellent surface) manufactured by SGL Carbon and one using a gas diffusion layer Sigracet GDL39AA (without a water-repellent surface) manufactured by SGL Carbon were prepared, and the test was performed on each. The electrolyte after the reaction was analyzed by gas chromatography (absolute calibration curve method) to calculate the yield of the target cyclic amine (piperidine), and the results shown in Table 7 below were obtained.

[0083]

[0084] As shown in Table 7, it can be seen that the yield of cyclic amine was better when the cathode substrate did not have a water-repellent surface treatment.

[0085] REFERENCE SIGNS LIST 10, 20 Cyclic amine production apparatus 11 Substrate supply section 12 Anion exchange membrane electrolysis unit 13 Anion exchange membrane 14a Cathode 14b Gasket 15, 18 Separator 16, 19 End plate 17a Anode 17b Gasket 21 Electrolyte supply section 22, 23, 24, 25 Piping 26 Substrate and electrolyte supply section

Claims

1. A substrate supply unit that supplies nitrogen-containing heteroaromatic compounds as substrates, An anion exchange membrane type electrolytic unit for producing a cyclic amine by electrolytically hydrogenating a substrate supplied from the substrate supply unit, Equipped with, The anion exchange membrane type electrolytic unit comprises a cathode containing a cathode catalyst layer, an anode containing a metal oxide, and an anion exchange membrane provided between the cathode and the anode, and the substrate supply unit supplies the substrate to the cathode. An apparatus for producing cyclic amines, wherein the cathode catalyst layer is composed of Co.

2. The apparatus for producing a cyclic amine according to Claim 1, wherein the substrate supply unit is a substrate and electrolyte supply unit containing the substrate and an electrolyte, and the electrolyte is supplied to the cathode together with the substrate from only the substrate and electrolyte supply unit.

3. A nitrogen-containing heteroaromatic compound, which is the substrate, is supplied to an anion exchange membrane electrolytic unit, and the anion exchange membrane electrolytic unit electrolyzes the supplied substrate to produce a cyclic amine. The anion exchange membrane type electrolytic unit comprises a cathode containing a cathode catalyst layer, an anode containing a metal oxide, and an anion exchange membrane provided between the cathode and the anode, wherein the substrate is supplied to the cathode. A method for producing a cyclic amine, wherein the cathode catalyst layer is composed of Co.

4. The method for producing a cyclic amine according to claim 3, wherein the electrolyte is supplied to the cathode together with the substrate from only a supply unit containing the substrate and the electrolyte.