WO2024043158A1

WO2024043158A1 - Device for producing cyclic amine and method for producing cyclic amine

Info

Publication number: WO2024043158A1
Application number: PCT/JP2023/029644
Authority: WO
Inventors: 真人跡部; 尚毅信田; 勇吾清水
Original assignee: 国立大学法人横浜国立大学
Priority date: 2022-08-25
Filing date: 2023-08-16
Publication date: 2024-02-29

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

Cyclic amine manufacturing device and cyclic amine manufacturing method

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

Cyclic amines are important skeletons included in most of the small molecule drugs approved by the Food and Drug Administration (FDA), and various cyclic amines have been produced in the past.

Piperidine, which is the most typical 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 a hydrogen source (Non-patent Document 1). ).

Conventionally, in the production of cyclic amines such as piperidine, an energy-intensive chemical hydrogenation process of nitrogen-containing heteroaromatic compounds, such as at high temperatures and high pressures, has been used. Further, in the hydrogenation, hydrogen gas is used as a raw material.

As described above, conventionally, in order to produce a cyclic amine, high energy conditions such as high temperature and high pressure, and hydrogen gas as a raw material were required.

In order to solve these problems, the present invention provides a cyclic amine production apparatus that can produce a cyclic amine by hydrogenating a nitrogen-containing heteroaromatic compound at room temperature and pressure without using hydrogen gas. An object of the present invention is to provide a method for producing a cyclic amine.

The above problem is solved by the present invention specified as follows.
(1) A substrate supply unit that supplies a nitrogen-containing heteroaromatic compound as a substrate, and an anion exchange membrane electrolysis unit that electrolytically hydrogenates the substrate supplied from the substrate supply unit to produce a cyclic amine. , cyclic amine production equipment.
(2) The anion exchange membrane type electrolysis unit includes 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. The apparatus for producing a cyclic amine according to (1), wherein the part supplies the substrate to the cathode.
(3) The cathode catalyst layer includes at least one catalyst metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. Cyclic amine manufacturing equipment.
(4) A cyclic amine in which a nitrogen-containing heteroaromatic compound as a substrate is supplied to an anion exchange membrane electrolysis unit, and the anion exchange membrane electrolysis unit electrolytically hydrogenates the supplied substrate to produce a cyclic amine. manufacturing method.
(5) The anion exchange membrane type 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 is The method for producing a cyclic amine according to (4), which is supplied to the cathode.
(6) The cathode catalyst layer includes at least one catalyst metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. A method for producing a cyclic amine.

According to the present invention, there is provided a cyclic amine production apparatus and a cyclic amine production method capable of producing a cyclic amine by hydrogenating a nitrogen-containing heteroaromatic compound at normal temperature and pressure without using hydrogen gas. can be provided.

1 is a schematic diagram of a cyclic amine manufacturing apparatus 10 according to Embodiment 1 of the present invention. 1 is a schematic developed view of an anion exchange membrane electrolysis unit 12 according to Embodiments 1 and 2 of the present invention. FIG. FIG. 2 is a schematic diagram of a cyclic amine manufacturing apparatus 20 according to Embodiment 2 of the present invention.

Next, embodiments for carrying out the present invention will be described in detail with reference to the drawings. It is understood that the present invention is not limited to the following embodiments, and that design changes, improvements, etc. may be made as appropriate based on the common knowledge of those skilled in the art without departing from the spirit of the present invention. Should.

・Embodiment 1
<Configuration of cyclic amine production equipment>
FIG. 1 shows a schematic diagram of a cyclic amine manufacturing 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 section 11, an electrolyte supply section 21, and

piping

22, 23, 24, and 25.

FIG. 2 shows a developed schematic diagram of the anion exchange membrane electrolysis unit 12 according to Embodiment 1 of the present invention. The anion exchange membrane type electrolysis unit 12 has an anion exchange membrane (AEM) 13, and from one side of the anion exchange membrane 13, a cathode 14a, a gasket 14b, a separator 15, and an end plate 16 are arranged in this order. Laminated. Further, 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 type electrolysis unit 12 is a laminate made of a plurality of members obtained in this way, and the plurality of members are fixed to each other by uniformly tightening bolts or the like at a plurality of locations.

The size of each of the above-mentioned members constituting the anion exchange membrane electrolysis unit 12 is not particularly limited, and can be formed to a desired size as necessary. As an example, for each of the above-mentioned members constituting the anion exchange membrane type electrolysis unit 12, the cathode 14a and the anode 17a are plate-shaped with dimensions of length x width x thickness = 1 to 5 cm x 3 to 10 cm x 50 to 1000 μm. Other than these, it may be a plate-like member having dimensions of length x width x thickness = 5 to 20 cm x 5 to 20 cm x 0.01 to 2 cm.

The anion exchange membrane 13 is not particularly limited, and any known anion exchange membrane can be used. The anion exchange membrane 13 is positively charged by a positive charge exchange group fixed to the membrane, and prevents the passage of cations and allows only anions to pass through.

The cathode 14a is embedded approximately in the center of a thin plate-shaped gasket 14b. The cathode 14a has a base material and a cathode catalyst layer provided on the surface of the base material. As the base material, a porous nickel material, a porous titanium material, a carbon woven cloth (carbon cloth), a carbon nonwoven cloth, carbon paper, etc. can be used. Carbon cloth is a bundle of several hundred thin carbon fibers with a diameter of several μm, and this bundle is made into a woven fabric. Carbon paper is made by using carbon raw material fibers as a thin film precursor using a paper manufacturing method, and then sintering this. Although the base material of the cathode 14a may have a water-repellent surface, it is more preferable to use a material whose surface is not water-repellent. The form of the cathode catalyst layer is not particularly limited, but a porous carbon material supporting a catalyst metal can be used. Examples of the porous carbon material of the cathode catalyst layer include an electron conductive material containing any one of porous carbon, porous metal, and porous metal oxide as a main component. Examples of porous carbon include carbon blacks such as Ketjenblack (registered trademark), acetylene black, furnace black, and Vulcan (registered trademark). Examples of the porous metal include Pt black, Pd black, and fractal-precipitated Pt metal. Examples of porous metal oxides include oxides of Ti, Zr, Nb, Mo, Hf, Ta, and W. In addition, the catalyst carrier may contain 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. Examples of the catalytic metal of the cathode catalyst 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 catalyst metal supported on the porous carbon material can be appropriately designed from the viewpoint of how efficiently the nitrogen-containing heteroaromatic compound as a substrate is hydrogenated and from the viewpoint of cost. It may be supported in an amount of about 50% by mass.

The method for producing the cathode 14a is not particularly limited. For example, first, a porous carbon material carrying a catalyst metal is mixed with a solution prepared by dispersing a solvent such as water or alcohol and an ionomer to obtain a catalyst slurry. The ionomer coats the catalyst carrier supporting the catalyst metal. Thereby, the ion conductivity of the cathode 14a can be improved. Examples of anion-conductive ionomers include polymers having strong basic groups (such as quaternary ammonium groups and imidazolium groups).

Next, the catalyst slurry is applied to the surface of a base material such as carbon paper and dried, and the catalyst slurry is further applied and dried repeatedly to form a cathode catalyst layer on the surface of the base material. In this way, the cathode 14a can be manufactured.

The gasket 14b is provided to prevent a solution containing a substrate supplied from the substrate supply section 11 to the cathode 14a, which will be described later, from leaking outside. The gasket 14b is not particularly limited as long as it is made of a material that does not react with the cathode 14a and the substrate. For example, a material made of Teflon (registered trademark) or a fluorine-based elastomer such as Viton (registered trademark) can be used.

The anode 17a is embedded approximately in the center of a thin plate-shaped gasket 17b. Although the form of the anode 17a is not particularly limited, a metal base material with a metal oxide attached to the surface can be used. The metal base material may be, for example, a mesh base material, a metal fiber, a sintered body of a porous metal body, a foam molded body, or an expanded metal, and may include Ti, Cr, Mn, Fe, Co, Ni, Cu, Metals having excellent corrosion resistance such as Zn, Nb, Mo, Ta, and W can be used. Examples of the metal oxide of the anode 17a include at least one catalyst selected from the group consisting of iridium oxide, ruthenium oxide, and tantalum oxide.

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

Both

separators

15 and 18 constitute a current collector. Both of the

separators

15 and 18 are made of carbon resin, Cr-Ni-Fe system, Cr-Ni-Mo-Fe system, Cr-Mo-Nb-Ni system, Cr-Mo-Fe-W-Ni system, or Ti system. It is possible to use a material made of a corrosion-resistant alloy such as

The

end plates

16 and 19 are each made of a conductive material. It is preferable that the

end plates

16 and 19 are members 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 source, and the end plate 19 is electrically connected to the positive terminal of the external power source.

The substrate supply unit 11 stores 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 section 11 in a state 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 section 11 as it is. It's okay. The organic solvent is not particularly limited, but it is preferable to use one that does not attack the anion exchange membrane, such as methyl tert-butyl ether, diisopropyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and the like. 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.

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

On the other hand, the piping 23 is provided so as to pass through the separator 15 and the end plate 16 from the cathode 14a, and a solution containing a cyclic amine produced by electrolytic hydrogenation of the substrate at the cathode 14a is passed from the anion exchange membrane electrolysis unit 12. be discharged. The piping 23 may also be connected to the substrate supply section 11 and configured to return the solution containing the cyclic amine to the substrate supply section 11. According to such a configuration, the solution containing the cyclic amine produced at the cathode 14a can be circulated between the substrate supply section 11 and the anion exchange membrane electrolysis unit 12. Therefore, even if the solution containing the cyclic amine generated at the cathode 14a contains an unreacted nitrogen-containing heteroaromatic compound, it can be repeatedly fed to the cathode 14a, so that it can be efficiently and completely reacted to form a cyclic amine. be able to.

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

A pipe 25 is connected to the electrolyte supply section 21, which serves as a supply path for water or a basic aqueous solution to the anion exchange membrane electrolysis unit 12. Piping 25 is provided to penetrate end plate 19 and separator 18, and water or basic aqueous solution passing through piping 25 is supplied to anode 17a. Water or basic aqueous solution can be supplied using a known pump or the like.

On the other hand, the pipe 24 is provided so as to pass through the separator 18 and the end plate 19 from the anode 17a, and the oxygen solution generated at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12. The pipe 24 may also be connected to the electrolyte supply section 21 and configured to return the oxygen solution to the electrolyte supply section 21 . According to such a configuration, the reaction system can be designed compactly.

<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 manufacturing apparatus 10 having the configuration shown in FIGS. 1 and 2 is prepared. A nitrogen-containing heteroaromatic compound as a substrate is placed in the substrate supply section 11, and water or a basic aqueous solution is placed in the electrolyte supply section 21.

Next, a nitrogen-containing heteroaromatic compound as a substrate is supplied from the substrate supply section 11 to the cathode 14a of the anion exchange membrane electrolysis unit 12 through the pipe 22 at room temperature and pressure. On the other hand, from the electrolyte supply section 21, water or a basic aqueous solution is supplied to the anode 17a of the anion exchange membrane type electrolysis unit 12 through the pipe 25 at room temperature and pressure. In the anion exchange membrane type electrolysis unit 12, an external power source is electrically connected to the

end plates

16 and 19, respectively, and an electrolysis reaction occurs at the cathode 14a and the anode 17a due to the current from the external power source.

In the electrolysis reaction of the cathode 14a, a cyclic amine is produced by electrolytically hydrogenating some or all of the unsaturated bonds of the aromatic ring of the nitrogen-containing heteroaromatic compound. Hydrogen active species generated on the catalytic metal of the cathode 14a by water electrolysis are used as the hydrogen source for the electrolytic hydrogenation, while in the electrolysis reaction of the anode 17a, electrons are released from hydroxide ions in the electrolytic solution, and oxygen and water are produced. The electrolysis reactions at the cathode 14a and anode 17a are shown in equations (1) and (2), respectively. In formulas (1) and (2), n represents a natural number. Further, 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.

A nitrogen-containing heteroaromatic compound is converted into a cyclic amine by electrolytic hydrogenation using the cyclic amine production apparatus 10 according to Embodiment 1 of the present invention, but the types of the nitrogen-containing heteroaromatic compound and the cyclic amine that is the product are particularly limited. Not done. The cyclic amine produced by the cyclic amine production apparatus 10 according to Embodiment 1 of the present invention has one or more nitrogen atoms in a 5-membered ring or a 6-membered ring, and is aliphatic or partially unsaturated. Examples include monocyclic or polycyclic cyclic amine compounds having saturated bonds. Further, specific examples of the nitrogen-containing heteroaromatic compound and cyclic amine are shown in formulas (3) to (17). The left sides of formulas (3) to (17) all indicate examples of the nitrogen-containing heteroaromatic compounds ((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, (17) 4-phenylpyridine). The right sides of formulas (3) to (17) all indicate examples of cyclic amines obtained by electrolytic hydrogenation of nitrogen-containing heteroaromatic compounds ((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, (17) 4-phenylpiperidine).

The cyclic amine produced by the cyclic amine production apparatus 10 according to Embodiment 1 of the present invention is produced by electrolytically hydrogenating some or all of the unsaturated bonds of the aromatic ring of the nitrogen-containing heteroaromatic compound. If any, compounds other than those mentioned above can also be mentioned. For example, cyclic amines such as 1,4-dihydropyridine, acridan, 5,6-dihydrophenanthridine, etc. can also be produced.

A solution containing a cyclic amine produced by electrolytically hydrogenating 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. On the other hand, the oxygen solution generated at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12 through the pipe 24. When the piping 23 is connected to the substrate supply section 11 , a solution containing a cyclic amine produced at the cathode 14 a is circulated between the substrate supply section 11 and the anion exchange membrane electrolysis unit 12 . By circulating in this way, even if the solution containing the cyclic amine generated at the cathode 14a contains an unreacted nitrogen-containing heteroaromatic compound, it can be repeatedly fed to the cathode 14a, so that the reaction can be completed efficiently. can be converted into a cyclic amine.

・Embodiment 2
<Configuration of cyclic amine production equipment>
FIG. 3 shows a schematic diagram of a cyclic amine manufacturing apparatus 20 according to Embodiment 2 of the present invention. The cyclic amine manufacturing apparatus 20 includes an anion exchange membrane electrolysis unit 12, a substrate and electrolyte supply section 26, and piping 22, 23, and 24. The cyclic amine manufacturing apparatus 20 is different from the cyclic amine manufacturing apparatus 10 according to the first embodiment in that the substrate and the electrolyte are simultaneously supplied to the cathode 14a.

The anion exchange membrane type electrolysis unit 12 used in the cyclic amine production apparatus 20 according to the second embodiment of the present invention has the same configuration as the anion exchange membrane type electrolysis unit 12 of the cyclic amine production apparatus 10 shown in the first embodiment. have.

The substrate and electrolyte supply section 26 stores a nitrogen-containing heteroaromatic compound as a substrate and supplies it to the anion exchange membrane type electrolysis unit 12. The nitrogen-containing heteroaromatic compound may be stored in the substrate and electrolyte supply unit 26 in a state dissolved in an organic solvent, and if the nitrogen-containing heteroaromatic compound is liquid at room temperature, the substrate and electrolyte supply unit 26 may be accommodated as is. The organic solvent is not particularly limited, but it is preferably one that does not attack the anion exchange membrane and is miscible with water, such as tetrahydrofuran, 2-methyltetrahydrofuran, and the like. 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.

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

On the other hand, the piping 23 is provided so as to pass through the separator 15 and the end plate 16 from the cathode 14a, and a solution containing a cyclic amine produced by electrolytic hydrogenation of the substrate at the cathode 14a is passed from the anion exchange membrane electrolysis unit 12. be discharged. The piping 23 may also be connected to the substrate and electrolyte supply section 26 and configured to return the solution containing the cyclic amine to the substrate and electrolyte supply section 26 . According to such a configuration, the solution containing the cyclic amine produced at the cathode 14a can be circulated between the substrate and electrolyte supply section 26 and the anion exchange membrane type electrolysis unit 12. Therefore, even if the solution containing the cyclic amine generated at the cathode 14a contains an unreacted nitrogen-containing heteroaromatic compound, it can be repeatedly fed to the cathode 14a, so that it can be efficiently and completely reacted to form a cyclic amine. be able to.

In addition to the above-mentioned nitrogen-containing heteroaromatic compound, the substrate and electrolyte supply section 26 further 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 thereof include a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, an ammonia aqueous solution, and the like. Furthermore, the concentration of the basic aqueous solution is not particularly limited, but it can be 10 to 1000 mM.

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

<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 manufacturing apparatus 20 having the configuration shown in FIGS. 2 and 3 is prepared. The substrate and electrolyte supply section 26 contains a nitrogen-containing heteroaromatic compound as a substrate, and water or a basic aqueous solution.

Next, the nitrogen-containing heteroaromatic compound as a substrate and water or a basic aqueous solution are simultaneously supplied from the substrate and electrolyte supply section 26 to the cathode 14a of the anion exchange membrane electrolysis unit 12 through the pipe 22 at room temperature and pressure. . In the anion exchange membrane type electrolysis unit 12, an external power source is electrically connected to the

end plates

In the electrolysis reaction of the cathode 14a, a cyclic amine is produced by electrolytically hydrogenating some or all of the unsaturated bonds of the aromatic ring of the nitrogen-containing heteroaromatic compound. Hydrogen active species generated on the catalytic metal of the cathode 14a by water electrolysis are used as the hydrogen source for the electrolytic hydrogenation, while in the electrolysis reaction of the anode 17a, electrons are released from hydroxide ions in the electrolytic solution, and oxygen and water are produced. 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. Further, 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. H ₂ O generated by the electrolysis reaction at the anode 17a is discharged from the pipe 24 as water vapor or water droplets.

A nitrogen-containing heteroaromatic compound is converted into a cyclic amine by electrolytic hydrogenation using the cyclic amine production apparatus 20 according to Embodiment 2 of the present invention, but the types of the nitrogen-containing heteroaromatic compound and the cyclic amine that is the product are particularly limited. However, the cyclic amine shown in Embodiment 1 can be mentioned.

A solution containing a cyclic amine produced by electrolytically hydrogenating 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. On the other hand, oxygen generated at the anode 17a is discharged from the anion exchange membrane electrolysis unit 12 through the pipe 24. When the piping 23 is connected to the substrate and electrolyte supply section 26 , the solution containing the cyclic amine generated at the cathode 14 a is circulated between the substrate and electrolyte supply section 26 and the anion exchange membrane electrolysis unit 12 . . By circulating in this way, even if the solution containing the cyclic amine generated at the cathode 14a contains an unreacted nitrogen-containing heteroaromatic compound, it can be repeatedly fed to the cathode 14a, so that the reaction is completed efficiently. can be converted into a cyclic amine.

Since the cyclic amine manufacturing apparatus 20 according to the second embodiment of the present invention has the substrate and electrolyte supply parts integrated into one as the "substrate and electrolyte supply part 26", the cyclic amine production apparatus 20 according to the first embodiment The manufacturing apparatus can be configured more compactly than the manufacturing apparatus 10, and the manufacturing process is simplified. Furthermore, even when using not only expensive noble metals (Pt, Pd, Rh) but also relatively inexpensive metals such as Co, Ni, and Fe as the cathode catalyst layer, cyclic amines can be produced with low electricity consumption and good yield. You can get it at In addition, there are no reports on the hydrogenation of pyridines at room temperature and pressure using Co, which is an inexpensive metal, including non-electrolytic systems. In this respect as well, it provides an extremely excellent reaction system.

<Effects of the cyclic amine production apparatus and cyclic amine production method>
Conventionally, the production of cyclic amines such as piperidine has used an energy-intensive chemical hydrogenation process of nitrogen-containing heteroaromatic compounds, such as at high temperatures and pressures. Furthermore, hydrogen gas has been used as a raw material for hydrogenation. On the other hand, in the cyclic

amine manufacturing apparatuses

10 and 20 and the cyclic amine manufacturing method according to Embodiments 1 and 2 of the present invention, the cyclic amine is manufactured by electrochemically using a nitrogen-containing heteroaromatic compound at room temperature and under normal pressure. This is achieved through hydrogenation. Further, in the cyclic

amine manufacturing apparatuses

10 and 20 and the cyclic amine manufacturing method according to Embodiments 1 and 2 of the present invention, the hydrogen active species generated on the catalyst metal by water electrolysis is used as the hydrogen source for hydrogenation. Therefore, the use of hydrogen gas is unnecessary.

Further, by using the anion exchange membrane type electrolysis unit 12 in the cyclic

amine production apparatuses

10 and 20, the desired electrolytic hydrogenation proceeds smoothly. Note that when a general-purpose proton exchange membrane electrolysis unit is used as the same solid polymer electrolysis unit, since both the substrate and the product are basic substances, neutralized salts are formed within the proton exchange membrane. The reaction does not proceed.

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

The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.

<Example 1>
1. Preparation of 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, for the cathode, 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 Co., Ltd., Rh supported amount: 28.9% by mass), in which rhodium as a catalyst metal was supported on porous carbon as a catalyst carrier, was weighed. Next, pure water, an anion ionomer solution (AS-4, manufactured by Tokuyama Co., Ltd., 2 to 10% by mass 1-propanol solution), and 1-propanol were added to an 80 mL Teflon (registered trademark) container along with Rh/KB. In addition, a dispersion liquid was prepared. The amount of the anion ionomer added was set so that the weight ratio (Ionomer/Carbon) of carbon, which is a support for the carbon-supported metal catalyst, was 0.8, assuming that the anion ionomer solution was 5% by mass. Further, pure water and 1-propanol were set so that the weight ratio of the solvent contained in the obtained slurry was pure water:1-propanol=1:99.
Ten zirconia balls with a diameter of 2.5 mm were placed in a Teflon (registered trademark) container, and mixed using a pot mill at 200 rpm for 20 minutes 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 about 10 minutes to evaporate the solvent. After drying, the weight of the carbon paper was measured, and further slurry was applied as needed. This process was repeated to produce a cathode so that the amount of metal supported was 0.5 mg/cm ² . A membrane electrode assembly (MEA) was prepared by using nickel foam as the prepared cathode and anode, and sandwiching an anion exchange membrane therebetween.
Finally, the stainless steel end plates on the cathode and anode sides, the carbon separator on the cathode side, the titanium separator on the anode side, the Teflon (registered trademark) gaskets on the cathode and anode sides, and the above-mentioned MEA are shown in Figure 2. An anion exchange membrane type electrolysis unit was created by assembling as shown and tightening with bolts. A torque wrench was used for the tightening operation, and eight locations were equally tightened with a force of 3.0 Nm.
The size (length x width x thickness) of each member is shown below.
・Each end plate: 10.5cm x 12.5cm x 1.2cm
・Each separator: 6.5cm x 8.5cm x 1.3cm
・Each gasket: 6.5cm x 8.5cm x 0.16cm
・Cathode: 1.0cm x 4.0cm x 240μm
・Anode: 1.0cm x 4.0cm x 120μm
・Anion exchange membrane: 2cm x 15cm x 28μm

2. Electrolysis Using the anion exchange membrane type electrolysis unit produced as described above, a cyclic amine production apparatus having the configuration shown in FIG. 1 was produced as follows, and electrolysis was performed.
That is, 10mM potassium hydroxide aqueous solution is put into the electrolyte supply section on the anode side, and the anode is pumped using a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smoothflow pump (manufactured by Takumina Co., Ltd.) at a flow rate of 2.0mL/min. supplied to. Further, the solution was circulated between the anode and the electrolyte supply section.
On the other hand, a solution of 50 mM pyridine (3 mL) dissolved in methyl tertiary butyl ether was supplied to the cathode substrate supply section on the cathode side at a flow rate of 2.0 mL/min using a microceram pump or a smooth flow pump. Further, the solution was circulated between the cathode and the substrate supply section.
In this state, electrolysis was performed at 50 mA/cm ² (200 mA was applied in this experiment because the geometric area of the electrode was 4 cm ² ) up to 30 F/mol (1 F/mol current was applied for about 1 minute, and 30 F/mol current was applied for about 1 minute). (Electrification takes approximately 36 minutes).
The electrolytes on the cathode side and the anode side in the electrolysis were both at room temperature, and the electrolysis was performed under normal pressure.
The yield of the target cyclic amine (piperidine) was calculated by analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method).

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

<Example 3>
An anion exchange membrane type electrolysis unit was prepared in the same manner as in Example 1, except that Pd was used instead of Rh as the catalyst metal in the cathode catalyst layer, and the amount of Pd supported in KB was 29.3% by mass, and electrolysis was carried out. , the yield of the target cyclic amine (piperidine) was calculated.

<Example 4>
An anion exchange membrane type electrolysis unit was prepared in the same manner as in Example 1, except that Pt was used instead of Rh as the catalyst metal in the cathode catalyst layer, and the amount of Pt supported in KB was 46.4% by mass, and electrolysis was carried out. , the yield of the target cyclic amine (piperidine) was calculated.

<Example 5>
An anion exchange membrane type electrolysis unit was prepared in the same manner as in Example 1, except that Co was used instead of Rh as the catalyst metal in the cathode catalyst layer, and the amount of Pt supported in KB was 20.3% by mass, and electrolysis was carried out. , the yield of the target cyclic amine was calculated.
Table 1 shows the yields of the cyclic amines (piperidines) obtained in Examples 1 to 5.

<Example 6>
An anion exchange membrane type electrolysis unit was prepared in the same manner as in Example 1, except that a DSE (registered trademark) oxygen generation electrode (manufactured by De Nora Permelec Co., Ltd.) was used as an anode instead of nickel foam, and electrolysis was performed. The yield of the target cyclic amine was calculated. Next, a solution of 50 mM pyridine (3 mL) dissolved in methyl tert-butyl ether was added to the substrate supply section on the cathode side again at a flow rate of 2.0 mL/min using a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.). (manufactured by Takumina Corporation) to the cathode, and electrolysis was performed in the same manner. The electrolysis was repeated six times in total, and the yield of the target cyclic amine was calculated for each time.
Table 2 shows the yield of the cyclic amine (piperidine) obtained in Example 6. According to Table 2, it was found that the yield of cyclic amine did not decrease even when the anion exchange membrane type electrolysis unit was used repeatedly.

<Example 7>
Using the anion exchange membrane type electrolysis unit produced as described above, a cyclic amine production apparatus having the configuration shown in FIG. 1 was produced as follows, and electrolysis was performed.
That is, 10mM potassium hydroxide aqueous solution is put into the electrolyte supply section on the anode side, and the anode is pumped using a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smoothflow pump (manufactured by Takumina Co., Ltd.) at a flow rate of 2.0mL/min. supplied to. Further, the solution was circulated between the anode and the electrolyte supply section.
On the other hand, a solution of 50 mM quinoline (3 mL) dissolved in diisopropyl ether was supplied to the cathode substrate supply section on the cathode side at a flow rate of 2.0 mL/min using a microceram pump or a smooth flow pump. Further, the solution was circulated between the cathode and the substrate supply section.
In this state, electrolysis was performed at 25 mA/cm ² (100 mA was applied in this experiment because the geometric area of the electrode was 4 cm ² ) up to 12, 16, and 20 F/mol (1 F/mol current was applied for about 2 minutes and 30 minutes). 20F/mol for about 50 minutes).
The electrolytes on the cathode side and the anode side in the electrolysis were both at room temperature, and the electrolysis was performed under normal pressure.
The yield of the target cyclic amine was calculated by analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method).
The yield of the cyclic amine (1,2,3,4-tetrahydroquinoline) obtained in Example 7 was 91%.

<Example 8>
1. Preparation of anion exchange membrane electrolysis unit An anion exchange membrane electrolysis unit was produced in the same manner as in Example 1, except that the amount of Rh supported in the cathode catalyst layer: Rh (Rh/KB) was 0.5 mg/ ^cm2 . .

2. Electrolysis Using the anion exchange membrane type electrolysis unit produced as described above, a cyclic amine production apparatus having the configuration shown in FIG. 3 was produced as follows, and electrolysis was performed. In addition, as substrates, pyridine, which is the substrate on the left side of the following formula (3'), and the substrates on the left side 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, (17) 4-phenylpyridine) were used.

First, a solution of 100 mM substrate (5 mL) dissolved in a solvent was poured into the substrate and electrolyte supply section on the cathode side, and the flow rate was 2.0 mL/min using a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.). (manufactured by Takumina Co., Ltd.) was used to supply the cathode. Further, the solution was circulated between the cathode and the substrate and electrolyte supply section. The solvent used is water for the reactions of the above formulas (3') and (11) to (16), and water is used for the reaction of the above formula (17) to improve the solubility of the substrate and product. :Tetrahydrofuran=1:1 (volume ratio) mixed solvent was used.
In this state, electrolysis was performed at 50 mA/cm ² up to a predetermined amount of current. The energization time and amount of energization are shown in Table 3.
Tests were conducted on the electrolytic solution in the electrolysis under normal pressure and at room temperature (25° C.).
By analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method), the target product, piperidine, which is a cyclic amine on the right side of the above formula (3'), and (11) to ( Cyclic amines on the right side of 17) ((11) 2-methylpiperidine, (12) 3-methylpiperidine, (13) 4-methylpiperidine, (14) 2-ethylpiperidine, (15) 2,6-dimethylpiperidine, The yields of (16) 3-piperidinecarboxamide and (17) 4-phenylpiperidine) were calculated, and the results were shown in Table 3 below.

<Example 9>
Using the cyclic amine manufacturing apparatus shown in FIG. 3 having the same configuration as in Example 8, electrolysis was carried out as follows.
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 Microceram was applied at a flow rate of 2.0 mL/min. It was supplied to the cathode using a pump (manufactured by Yamazen Co., Ltd.) or a smooth flow pump (manufactured by Takumina Co., Ltd.). Further, the solution was circulated between the cathode and the substrate and electrolyte supply section.
As the substrate, 4-phenylpyridine, which is the substrate on the left side of the above formula (17), was used.
In this state, electrolysis was performed at 50 mA/cm ² to 14.9 F/mol. The energization time was 1 hour.
Tests were conducted on the electrolytic solution in the electrolysis at room temperature (25°C), 40°C, and 50°C under normal pressure.
The yield of the target cyclic amine (4-phenylpiperidine) was calculated by analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method), and the results are shown in Table 4 below. became.

As shown in Table 4, when 4-phenylpyridine is used as the substrate and Rh supported on Ketjen black (KB, registered trademark) (Rh/KB) is used as the cathode catalyst layer, as the reaction temperature increases, It was found that the yield of cyclic amines tends to be better.

<Example 10>
FIG. 3 shows a structure similar to that of Example 8, except that Co supported on Ketjen black (KB, registered trademark) (Co/KB, Co supported amount: 0.35 mg/cm ² ) was used as the cathode catalyst layer. Electrolysis was carried out as follows using the cyclic amine production apparatus shown in .
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 a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.) was added at a flow rate of 2.0 mL/min. (manufactured by Takumina Co., Ltd.) was used to supply the cathode. Further, the solution was circulated between the cathode and the substrate and electrolyte supply section.
In this state, electrolysis was performed at 20 mA/cm ² up to 18 F/mol. The current application time was 3 hours.
A test was conducted on the electrolytic solution in the electrolysis at room temperature (25° C.) under normal pressure.
The yield of the target cyclic amine (piperidine), which was calculated by gas chromatography (absolute calibration curve method) using the electrolyte solution after the reaction, was 90%. This yield is dramatically higher than the yield of cyclic amine (piperidine) of 61% in Example 5, which used the cyclic amine production apparatus configured as shown in Figure 1 and used Co/KB as the cathode catalyst layer. It can be seen that this has improved.

<Example 11>
FIG. 3 shows a structure similar to that of Example 8, except that Co supported on Ketjen black (KB, registered trademark) (Co/KB, Co supported amount: 0.5 mg/cm ² ) was used as the cathode catalyst layer. Electrolysis was carried out as follows using the cyclic amine production apparatus shown in .
That is, a solution of 100 mM pyridine (5 mL) dissolved in water was put into the substrate and electrolyte supply section on the cathode side, and a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.) was added at a flow rate of 2.0 mL/min. (manufactured by Takumina Co., Ltd.) was used to supply the cathode. Further, the solution was circulated between the cathode and the substrate and electrolyte supply section.
In this state, electrolysis was performed at 25 mA/cm ² up to 6 F/mol. The energization time was 1 hour.
Tests were conducted on the electrolytic solution in the electrolysis at room temperature (25°C), 40°C, and 60°C under normal pressure.
The yield of the target cyclic amine (piperidine) was calculated by analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method), and the results were shown in Table 5 below.

As shown in Table 5, when pyridine is used as the substrate and Co (Co/KB) supported on Ketjenblack (KB, registered trademark) is used as the cathode catalyst layer, when the reaction temperature decreases, the cyclic amine It was found that the yield tends to be better.

<Example 12>
Electrolysis was carried out as follows using the cyclic amine manufacturing apparatus shown in FIG. 3, which had the same configuration as 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 a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.) was added at a flow rate of 2.0 mL/min. (manufactured by Takumina Co., Ltd.) was used to supply the cathode. Further, the solution was circulated between the cathode and the substrate and electrolyte supply section. The amount of Co supported on the cathode catalyst layer was 0.2 mg/cm ² , 0.35 mg/cm ² , 0.5 mg/cm ² , and 1 mg/cm ² , respectively.
In this state, electrolysis was performed at 25 mA/cm ² up to 6 F/mol. The energization time was 1 hour.
A test was conducted on the electrolytic solution in the electrolysis at room temperature (25° C.) under normal pressure.
The yield of the target cyclic amine (piperidine) was calculated by analyzing the electrolyte solution after the reaction by gas chromatography (absolute calibration curve method), and the results were shown in Table 6 below.

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

<Example 13>
Electrolysis was carried out as follows using the cyclic amine production apparatus shown in FIG. 3, which had the same configuration as Example 11 (cathode catalyst layer: Co/KB) except for the cathode base material.
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 a Microceram pump (manufactured by Yamazen Co., Ltd.) or a Smooth Flow pump (manufactured by Yamazen Co., Ltd.) was added at a flow rate of 2.0 mL/min. (manufactured by Takumina Co., Ltd.) was used to supply the cathode. Further, the solution was circulated between the cathode and the substrate and electrolyte supply section.
In this state, electrolysis was performed at 25 mA/cm ² up to 6 F/mol. The energization time was 1 hour.
A test was conducted on the electrolytic solution in the electrolysis at room temperature (25° C.) under normal pressure. As the cathode base material, one uses a gas diffusion layer Sigracet (registered trademark) GDL39BB manufactured by SGL Carbon (with a water-repellent finish on the surface), and the other uses a gas diffusion layer Sigracet GDL39AA (without a water-repellent finish on the surface) manufactured by SGL Carbon. The test was conducted on each test.
The yield of the target cyclic amine (piperidine) was calculated by analyzing the electrolytic solution after the reaction by gas chromatography (absolute calibration curve method), and the results were shown in Table 7 below.

As shown in Table 7, it can be seen that the yield of cyclic amine was better when the surface of the cathode base material was not water-repellent.

10, 20 Cyclic amine manufacturing apparatus 11 Substrate supply section 12 Anion exchange membrane type 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

a substrate supply unit that supplies a nitrogen-containing heteroaromatic compound as a substrate;
an anion exchange membrane electrolysis unit that electrolytically hydrogenates the substrate supplied from the substrate supply unit to produce a cyclic amine;
Cyclic amine production equipment equipped with
The anion exchange membrane type electrolysis unit includes 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 includes: The cyclic amine manufacturing apparatus according to claim 1, wherein the substrate is supplied to the cathode.
The cyclic amine according to claim 2, wherein the cathode catalyst layer contains at least one catalyst metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. manufacturing equipment.
A method for producing a cyclic amine, wherein a nitrogen-containing heteroaromatic compound as a substrate is supplied to an anion exchange membrane electrolysis unit, and the anion exchange membrane electrolysis unit electrolytically hydrogenates the supplied substrate to produce a cyclic amine. .
The anion exchange membrane type 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 is attached to the cathode. A method for producing a cyclic amine according to claim 4, wherein the cyclic amine is supplied.
The cyclic amine according to claim 5, wherein the cathode catalyst layer contains at least one catalyst metal selected from the group consisting of Co, Ni, Fe, Cu, Ag, Ru, Pd, Ir, Pt, Au, and Rh. manufacturing method.