JP7514465B2 - Method for producing amine compound - Google Patents

Description

The present invention relates to a method for producing an amine compound.

Cyclopentylaminoethanol is useful as a carbon dioxide absorbent. It can be produced by hydrogenation of the double bond of cyclopentyl-2-iminoethanol.

Here, as a method for producing a compound using hydrogenation of a double bond, Patent Document 1 discloses a method for producing a reaction product by introducing microbubbles or nanobubbles (ultrafine bubbles) into a liquid phase consisting of a solvent and a substrate, and producing a reaction product produced by gas-liquid contact of the substrate with hydrogen in the presence of a solid catalyst. Patent Document 2 discloses a method for producing cyclohexane by reacting an emulsion of benzene and hydrogen gas bubbles formed using a high shear device in the presence of a solid catalyst. Patent Document 3 discloses an apparatus for hydrogenating aldehydes and/or ketones, configured to form a dispersion of hydrogen-containing bubbles in a liquid phase using a high shear device. Patent Document 4 discloses a chemical reaction between a raw material compound and a gas in the form of microbubbles or nanobubbles in a liquid containing an immiscible liquid medium. Patent Document 5 discloses a method for producing an aromatic amine compound by contacting an aromatic nitro compound with hydrogen microbubbles.

JP 2013-023460 A JP 2010-531882 A JP 2013-014595 A JP 2017-019743 A JP 2014-005217 A

Normally, to increase the efficiency of the hydrogenation process, the reaction is carried out in a batchwise manner in the presence of a catalyst at high temperature and pressure until the desired conversion rate is reached. However, high temperature and high pressure reactions require high equipment costs, and batch-type reactions have the drawback of limited productivity. For the hydrogenation process in the production of cyclopentylaminoethanol, a reaction system is required that can efficiently hydrogenate at low pressures, which overcomes the above challenges.

The inventors then came up with the idea that hydrogen could be made finely bubbled to enable efficient hydrogenation reactions at low pressures, and began to investigate the possibility. As a result, the inventors discovered that hydrogenation can proceed efficiently at low pressures by mixing finely bubbled hydrogen with a circulating liquid of cyclopentyl-2-iminoethanol and reacting it. Based on the new findings described above, the inventors have completed the present invention.

Thus, the present invention provides the following method for producing an aminoethanol compound.

[1] A method for producing an amine compound, comprising the step of supplying fine hydrogen bubbles and hydrogenating an imine compound in the presence of a solvent.
[2] The method according to the above [1], wherein the amine compound is a hydroxyalkylamine compound and the imine compound is a hydroxyalkylimine compound.
[3] The method according to [2] above, wherein the amine compound is an aminoethanol compound and the imine compound is an iminoethanol compound.
[4] The method according to any one of [1] to [3] above, wherein the imine compound has a hydrocarbon ring.
[5] The method according to any one of [1] to [4] above, wherein the solvent is an alcohol.

The present invention provides a method for producing an amine compound that can efficiently hydrogenate an imine compound under low pressure.

FIG. 1 is a schematic diagram showing an example of a hydrogenation reaction system (circulation-type hydrogenation reaction system) used in the present invention. FIG. 2 is a schematic diagram showing an example of a conventional hydrogenation reaction system using a centrifugal pump type bubble generating device and the like.

The present invention is described in detail below.

(Method for producing amine compound)
The method for producing an amine compound of the present invention includes a step of supplying fine hydrogen bubbles and hydrogenating an imine compound in a solvent. The production method of the present invention utilizes a reaction represented by the following formula in which a carbon atom-nitrogen atom double bond in an imine compound is hydrogenated (hydrogenated) to convert the imine compound into an amine compound. The production method of the present invention can efficiently hydrogenate an imine compound. Therefore, at least one of the following effects can be obtained: milder pressure during the hydrogenation reaction, improved hydrogenation rate, reduced amount of hydrogenation catalyst used, shorter hydrogenation reaction time, and lower hydrogenation reaction temperature.

<Product: Amine compound>
The amine compound produced by the production method of the present invention is a compound represented by the following formula.

In the formula, R ¹ is a hydrogen atom or an arbitrary substituent.

Examples of the substituent represented by R ¹ include a hydrocarbon group which may be substituted. Since the amine compound is obtained by a hydrogenation reaction, the substituent is preferably a saturated substituent. Examples of the saturated substituent include a saturated hydrocarbon group which may be substituted. Examples of the "saturated hydrocarbon group" of the saturated hydrocarbon group which may be substituted include linear alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, and icosyl, branched alkyl such as isopropyl, isobutyl, 1-methylpentyl, 1-ethylpentyl, sec-butyl, t-butyl, isopentyl, neopentyl, and isohexyl, and cyclic alkyl such as cyclopropyl and cyclobutyl. The number of carbon atoms of the "saturated hydrocarbon group" is preferably 1 to 20, and more preferably 1 to 6.
Examples of the optionally substituted saturated hydrocarbon group include saturated hydrocarbon groups optionally substituted with a hydroxy group or an alkoxy group.
R ¹ is preferably a saturated hydrocarbon group substituted with a hydroxy group, more preferably a hydroxy C1-20 alkyl group, even more preferably a hydroxy C1-6 alkyl group, still more preferably a hydroxy C1-6 linear alkyl group, and most preferably a 2-hydroxyethyl group.

In the formula, ^R2 and ^R3 may independently be a hydrogen atom or any substituent, or may be taken together to form a ring structure.

When R ² and R ³ are independently a hydrogen atom or any substituent, examples of the substituent include a hydrocarbon group which may be substituted. Since the amine compound is obtained by a hydrogenation reaction, the substituent is preferably a saturated substituent. Examples of the saturated substituent include a saturated hydrocarbon group which may be substituted. Examples of the "saturated hydrocarbon group" of the saturated hydrocarbon group which may be substituted include linear alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, and icosyl, branched alkyl such as isopropyl, isobutyl, 1-methylpentyl, 1-ethylpentyl, sec-butyl, t-butyl, isopentyl, neopentyl, and isohexyl, and cyclic alkyl such as cyclopropyl and cyclobutyl. The number of carbon atoms of the "saturated hydrocarbon group" is preferably 1 to 20, and more preferably 1 to 6.
An example of the optionally substituted saturated hydrocarbon group is a saturated hydrocarbon group optionally substituted with a hydroxy group.

When ^R2 and ^R3 together form a ring structure, examples of the ring structure consisting of the ^R2 -C- ^R3 portion include an optionally substituted hydrocarbon ring. Since the amine compound is obtained by a hydrogenation reaction, the ring structure consisting of the ^R2 -C- ^R3 portion is preferably a saturated ring structure. Examples of the saturated ring structure include an optionally substituted saturated hydrocarbon ring. Examples of the "saturated hydrocarbon ring" of the optionally substituted saturated hydrocarbon ring include cycloalkanes such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, and cyclodecane, and cycloalkanes having 1 to 20 carbon atoms are preferred, and cycloalkanes having 1 to 6 carbon atoms are more preferred.
Examples of the optionally substituted saturated hydrocarbon ring include saturated hydrocarbon rings optionally substituted with a hydroxy group or an alkoxy group.

It is preferable that R ² and R ³ together form a ring structure. The ring structure consisting of the R ² -C-R ³ portion is preferably an optionally substituted hydrocarbon ring, more preferably an optionally substituted saturated hydrocarbon ring, even more preferably an optionally substituted cycloalkane, even more preferably an optionally substituted cycloalkane having 1 to 20 carbon atoms, even more preferably an optionally substituted cycloalkane having 1 to 6 carbon atoms, even more preferably an optionally substituted cyclopentane, and most preferably cyclopentane.

The amine compound is preferably a hydroxyalkylamine compound, more preferably an aminoethanol compound, even more preferably a hydrocarbon ring-aminoethanol compound, even more preferably a saturated hydrocarbon ring-aminoethanol compound, even more preferably a cycloalkylaminoethanol, even more preferably a C1-20 cycloalkyl-aminoethanol, even more preferably a C1-6 cycloalkyl-aminoethanol, and most preferably cyclopentylaminoethanol.

The production method of the present invention is preferably carried out with a high hydrogenation rate (reaction yield). The hydrogenation rate is not particularly limited, but is preferably 90% or more, more preferably 95% or more, and even more preferably 99% or more. The hydrogenation rate in the hydrogenation reaction can be measured, for example, by a method using chromatography (e.g., GC-FID), NMR, or IR (specific examples include the methods described in the Examples of this specification).

<Raw material: Imine compound>
The imine compound used as a raw material in the production method of the present invention is a compound represented by the following formula.

In the formula, R ¹ ', R ² ', and R ³ ' may be the same as R ¹ , R ² , and R ³ , respectively, or may be a group in which the saturated bonds in R ¹ , R ² , and R ³ are replaced with unsaturated bonds. From the viewpoint of improving production efficiency such as quality, purity, and yield of the produced amine compound, it is preferable that R ¹ ', R ² ', and R ³ ' are the same as R ¹ , R ² , and R ³ , respectively.

When the amine compound is a hydroxyalkylamine compound, the imine compound is preferably a corresponding hydroxyalkylimine compound. When the amine compound is an aminoethanol compound, the imine compound is preferably a corresponding iminoethanol compound. When the amine compound is a hydrocarbon ring-aminoethanol compound, the imine compound is preferably a corresponding hydrocarbon ring-iminoethanol compound. When the amine compound is a saturated hydrocarbon ring-aminoethanol compound, the imine compound is preferably a corresponding saturated hydrocarbon ring-iminoethanol compound. When the amine compound is a cycloalkylaminoethanol, the imine compound is preferably a corresponding cycloalkyliminoethanol. When the amine compound is a C1-20 cycloalkyl-aminoethanol, the imine compound is preferably a corresponding C1-20 cycloalkyl-iminoethanol. When the amine compound is a C1-6 cycloalkyl-aminoethanol, the imine compound is preferably a corresponding C1-6 cycloalkyl-iminoethanol. When the amine compound is a cyclopentylaminoethanol, the imine compound is preferably a cyclopentyliminoethanol.

The concentration of the imine compound (raw material) in the solvent may be, for example, 0.1% (g/L) or more, preferably 0.5% (w/v) or more, more preferably 1.0% (w/v) or more, and may be, for example, 30% (w/v) or less, preferably 20% (w/v) or less, more preferably 15% (w/v) or less.

<Solvent>
The solvent can be appropriately selected depending on the solubility of the imine compound (raw material) and the amine compound (product). For example, aliphatic hydrocarbons such as n-pentane, n-hexane, and n-heptane; alicyclic hydrocarbons such as cyclopentane, cyclohexane, methylcyclohexane, dimethylcyclohexane, trimethylcyclohexane, ethylcyclohexane, diethylcyclohexane, decahydronaphthalene, bicycloheptane, tricyclodecane, hexahydroindene, and cyclooctane; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene; nitrogen-containing hydrocarbons such as nitromethane, nitrobenzene, acetonitrile, propionitrile, and benzonitrile; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as diethyl ether, dibutyl ether, tetrahydrofuran, and dioxane; and alcohols such as methanol and ethanol can be used. Alcohols are preferred, and methanol is more preferred. Furthermore, the solution in which the raw material (imine compound) or the product (amine compound) is dissolved in a solvent is collectively referred to as the "reaction liquid" for convenience.

<Hydrogen fine bubbles>
"Fine bubbles" refers to bubbles with a diameter of 100 μm or less. The formation of fine bubbles can also be defined as an index of the number of bubbles contained in a unit volume of liquid. For example, if the number of bubbles per 1 mL of liquid is 1.0 × 10 ⁷ or more, it can be considered that fine bubbles advantageous for reaction have been formed. The number of bubbles per 1 mL of liquid may be 1.0 × 10 ⁷ or more, preferably 2.0 × 10 ⁷ or more, and more preferably 3.0 × 10 ⁷ or more. The number of bubbles can be measured, for example, using a nanosite manufactured by Quantum Design Co., Ltd.

Making hydrogen gas into fine bubbles has the following advantages over making it into bubbles (non-fine bubbles) with a diameter larger than 100 μm. Fine bubbles have a larger surface area of the gas-liquid interface of the same volume of hydrogen gas compared to non-fine bubbles, so the area of gas-liquid contact is increased. In addition, non-fine bubbles tend to rise in liquid and be released out of the liquid, or to adhere to the wall of a container, etc., and are therefore easily separated from the liquid, whereas fine bubbles, as explained by the Stokes equation, rise very slowly in liquid and remain in liquid for a long time, increasing the time of gas-liquid contact. These effects increase the rate of consumption of hydrogen gas in the reaction, improving the reaction efficiency and suppressing the increase in pressure due to the generation of unreacted hydrogen gas. In addition, fine bubbles are said to be able to obtain energy that locally promotes the reaction because they self-collapse and release energy. Furthermore, by converting hydrogen gas into fine bubbles, there is no need to apply high pressure to the reaction system, and pressure increases in the reaction system due to the release of bubbles are suppressed, which also suppresses deterioration of the reaction equipment due to high pressure.

<Supply of Hydrogen Fine Bubbles>
Hydrogen fine bubbles can be generated by using a continuous flow type fine bubble generator. A continuous flow type fine bubble generator is a device that uses a pressurized and decompressed generation method/gas-liquid two-phase flow shear method to continuously inflow a reaction liquid and hydrogen gas and continuously discharge a reaction liquid containing hydrogen fine bubbles. A continuous flow type fine bubble generator is preferably a device that generates fine bubbles by shear force using the flow rate of a fluid without using external mechanical power. An example of a continuous flow type fine bubble generator is a micromixer.
The micromixer preferably has a shape that allows two or more flow paths to collide evenly so that the liquid and gas can be mixed evenly.
The flow rate of the reaction liquid to the micromixer may be, for example, 0.1 mL/min or more, preferably 0.5 mL/min or more, more preferably 1.0 mL/min or more, and may be, for example, 20 mL/min or less, preferably 15 mL/min or less, more preferably 10 mL/min or less.
The flow rate of hydrogen gas to the micromixer may be, for example, 0.1 mL/min or more, preferably 0.2 mL/min or more, more preferably 0.5 mL/min or more, and may be, for example, 10 mL/min or less, preferably 5 mL/min or less, more preferably 3 mL/min or less.
The volume ratio of the hydrogen gas flow rate to the reaction liquid flow rate may be, for example, 0.01 or more, preferably 0.1 or more, more preferably 0.5 or more, and may be, for example, 15 or less, preferably 10 or less, more preferably 5 or less.
The fine bubble generating pressure may be, for example, 0.1 MPa or more, preferably 0.2 MPa or more, more preferably 0.5 MPa or more, and may be, for example, 10 MPa or less, preferably 8 MPa or less, more preferably 5 MPa or less.
Fine bubble generation using a micromixer is advantageous in that it does not require harsh conditions such as high pressure, and is highly applicable to a circulating reaction system, compared to bubble generation using, for example, a centrifugal pump type bubble generator (JP Patent Publication 2006-159187 A). In addition, a circulating reaction system has the advantages of being able to successively supply a large amount of hydrogen compared to a batch reaction system that has a limit to the amount of hydrogen that can be supplied at one time, and that it is possible to operate while monitoring the hydrogenation rate.

<Hydrogenation reaction>
The hydrogenation reaction is carried out by placing the reaction solution containing fine hydrogen bubbles under conditions suitable for the hydrogenation reaction. Preferably, the hydrogenation reaction is carried out by transferring the reaction solution containing fine hydrogen bubbles to a hydrogenation reaction vessel under conditions suitable for the hydrogenation reaction. As represented by the following formula, the hydrogenation reaction is a reaction in which the carbon-nitrogen double bond in the imine compound, which is the raw material, is hydrogenated (hydrogenated) to convert it into the amine compound, which is the product. The hydrogenation reaction is preferably carried out in the presence of a hydrogenation catalyst.

<Hydrogenation catalyst>
The hydrogenation catalyst is not particularly limited and may be a homogeneous catalyst, a heterogeneous catalyst, or the like, and any known catalyst used in the hydrogenation reaction of a compound having an unsaturated bond may be used. The hydrogenation catalyst is preferably a solid catalyst.

Examples of homogeneous catalysts include Ziegler catalysts composed of combinations of cobalt acetate and triethylaluminum, nickel acetylacetonate and triisobutylaluminum, titanocene dichloride and n-butyllithium, zirconocene dichloride and sec-butyllithium, tetrabutoxytitanate and dimethylmagnesium, and the like; ruthenium carbene complex catalysts; chlorotris(triphenylphosphine)rhodium (Wilkinson's catalyst); and noble metal complex catalysts composed of ruthenium compounds described in JP-A-7-2929, JP-A-7-149823, JP-A-11-158256, JP-A-11-193323, and the like.
As the heterogeneous catalyst, either a catalyst containing only an active component, or a catalyst containing an active component and a carrier for supporting the active component can be used.
Active components include metals such as nickel, palladium, platinum, rhodium, and ruthenium.
The support may include carbon, silica, diatomaceous earth, alumina, titanium oxide, and the like.
Specific examples of catalysts containing only active components include Raney catalysts such as Raney nickel, Raney palladium, and Raney platinum.
Specific examples of catalysts containing an active component and a support include nickel/silica, nickel/diatomaceous earth, nickel/alumina, palladium/carbon, palladium/silica, palladium/diatomaceous earth, and palladium/alumina.
These hydrogenation catalysts may be used alone or in combination of two or more kinds.

As the hydrogenation catalyst, it is preferable to use a catalyst containing metallic nickel, such as Raney nickel or a metallic nickel supported catalyst (e.g., nickel/silica, nickel/diatomaceous earth, nickel/alumina), and it is more preferable to use a metallic nickel supported catalyst. If a catalyst containing metallic nickel is used as the hydrogenation catalyst, compounds having unsaturated bonds can be hydrogenated more efficiently.

The amount of the hydrogenation catalyst used in the hydrogenation reaction step is preferably 0.01 parts by mass or more, more preferably 0.05 parts by mass or more, and even more preferably 0.1 parts by mass or more, relative to 100 parts by mass of the imine compound as the raw material, and is preferably 50 parts by mass or less, more preferably 20 parts by mass or less, and even more preferably 10 parts by mass or less.
The amount of catalyst used refers to the amount of catalyst used in a dry state, including the carrier.

The loading amount (volume) of the hydrogenation catalyst is preferably 0.01% or more, more preferably 0.05% or more, and even more preferably 0.1% or more, and is preferably 5% or less, more preferably 2% or less, and even more preferably 1% or less, relative to the volume of the hydrogenation reaction vessel.

<Hydrogenation reaction conditions>
The hydrogenation reaction is carried out by placing the reaction solution containing hydrogen fine bubbles under a predetermined condition, preferably by transferring the reaction solution containing hydrogen fine bubbles to a hydrogenation reactor. The hydrogenation reactor may be either a continuous hydrogenation reactor or a batch hydrogenation reactor, but a continuous reactor is preferred from the viewpoint of efficiency. An example of a continuous reactor is a tube with a hydrogenation catalyst fixed thereto (a catalyst fixed tube).

The temperature at which the hydrogenation reaction is carried out (i.e., the temperature of the hydrogenation reaction vessel) can be set appropriately taking into consideration the temperature suitable for the hydrogenation reaction, the melting point and boiling point of the solvent, etc. The temperature at which the hydrogenation reaction is carried out is preferably equal to or higher than the melting point of the solvent. The temperature at which the hydrogenation reaction is carried out may be, for example, 10°C or higher, preferably 15°C or higher, and more preferably 20°C or higher. The temperature at which the hydrogenation reaction is carried out is preferably equal to or lower than the boiling point of the solvent. The temperature at which the hydrogenation reaction is carried out may be, for example, 100°C or lower, preferably 80°C or lower, and more preferably 60°C or lower.

The time for carrying out the hydrogenation reaction (in the case of a continuous reactor, the time for the reaction liquid to pass through the reactor) may be, for example, 0.1 h or more, preferably 1 h or more, more preferably 3 h or more, and may be, for example, 24 h or less, preferably 18 h or less, more preferably 12 h or less.

When a continuous reactor is used as the hydrogenation reaction vessel, the flow rate of the reaction liquid containing hydrogen fine bubbles may be, for example, 0.1 mL/min or more, preferably 0.5 mL/min or more, more preferably 1 mL/min or more, and may be, for example, 20 mL/min or less, preferably 18 mL/min or less, more preferably 15 mL/min or less.

The hydrogenation reactor may be loaded with a hydrogenation catalyst. The hydrogenation catalyst may be packed in the hydrogenation reactor or may be fixed in the hydrogenation reactor. The hydrogenation reactor may have a filter to prevent the hydrogenation catalyst from escaping.

The flow rate ratio per hour of the reaction liquid containing fine hydrogen bubbles per volume of the catalyst (liquid space linear velocity hr ⁻¹ ) may be, for example, 0.1 hr ⁻¹ or more, preferably 0.2 hr ⁻¹ or more, more preferably 0.5 hr ⁻¹ or more, and may be, for example, 300 hr ⁻¹ or less, preferably 200 hr ⁻¹ or less, more preferably 150 hr ⁻¹ .

<Hydrogenation reaction system>
The production method of the present invention may be carried out using any of reaction systems such as a circulation type reaction system, a batch type reaction system, and a semi-batch type reaction system. Hydrogenation using fine bubbles may cause undesirable hydrogenation to proceed excessively due to high hydrogenation efficiency. In order to suppress undesirable hydrogenation, it is preferable to monitor the hydrogenation rate and control the hydrogenation from the hydrogenation rate. From this viewpoint, the reaction system is preferably a circulation type reaction system. An example of the circulation type reaction system is a reaction system in which a fine bubble generator and a hydrogenation reaction vessel (e.g., catalyst fixed tube) are arranged on a circulation flow path through which the reaction liquid flows. A specific example of the circulation type reaction system is a reaction system having a configuration shown in the schematic diagram of FIG. 1. In the schematic diagram of FIG. 1, the reaction liquid held in the vessel 1 is discharged from the reaction liquid discharge section 2, circulated through the pump 3, the hydrogen gas junction section 4, the heating oven 5, the fine bubble generator 6 (e.g., micromixer), the reaction liquid back pressure regulator 7, and the hydrogenation reaction vessel 8 (e.g., catalyst fixed tube) in this order, and collected in the vessel 1 by the reaction liquid recovery section 9. In the schematic diagram of Figure 1, hydrogen gas supplied from a hydrogen gas supply unit 10 passes through a hydrogen gas flow regulator 11 and merges with the reaction liquid at a hydrogen gas merging unit 4. The circulating reaction system may further include a flow meter, a pressure meter, and a hydrogenation rate monitoring means at any position. Each component of the circulating reaction system shown in Figure 1 will be described below.

The container 1 is a container for holding a reaction liquid. The shape of the container 1 can be a closed container or an open container. Preferably, the container 1 may be a closed container from the viewpoint of preventing impurities from being mixed in and controlling the reaction. Examples of the material of the container 1 include metal, glass, and resin. When the container 1 is a closed container, the container 1 is preferably made of metal from the viewpoint of pressure resistance. When the container 1 is a closed container, the reaction liquid may be filled in the container 1 fully or may be filled with gaps, but it is preferable that the reaction liquid is filled with gaps from the viewpoint of accumulation of unreacted hydrogen gas. From the viewpoint of suppressing unintended reactions, the container 1 is preferably sufficiently dry. From the same viewpoint, the container 1 is preferably substituted with an inert gas (e.g., nitrogen; rare gases such as helium, neon, argon, krypton, and xenon).

The reaction liquid discharge section 2 is a section for discharging the reaction liquid from the container 1. The reaction liquid discharge section 2 may include a filter to prevent the inclusion of solid impurities.

The pump 3 is a device for generating a circulating flow of the reaction liquid. From the viewpoint of suppressing the loss of hydrogen fine bubbles from the reaction liquid due to mechanical stimulation, it is preferable that the pump 3 is connected upstream of the hydrogen gas junction 4.

The reaction liquid back pressure regulator 7 is a device that keeps the back pressure of the reaction liquid constant. By keeping the back pressure of the reaction liquid constant, the reaction liquid back pressure regulator 7 keeps the flow rate of the reaction liquid constant and maintains constant reaction conditions. As the reaction liquid back pressure regulator 7, for example, a general liquid back pressure regulator such as a back pressure valve or a pressure control valve can be used.

The reaction liquid recovery section 9 is a section for recovering the circulated reaction liquid into the container 1.

The hydrogen gas supply unit 10 is a source of hydrogen gas for the circulating hydrogenation reaction device. An example of the hydrogen gas supply unit 10 is a hydrogen gas cylinder.

The hydrogen gas flow regulator 11 is a device that stabilizes the back pressure of the hydrogen gas supplied from the hydrogen gas supply unit 10. The hydrogen gas flow regulator 11 stabilizes the amount of hydrogen gas supplied and maintains constant reaction conditions by stabilizing the back pressure of the hydrogen gas. As the hydrogen gas flow regulator 11, for example, a general gas back pressure regulator such as a back pressure valve or a pressure control valve can be used.

The circulation flow rate of the reaction liquid can be adjusted by the pump 3 and the reaction liquid back pressure regulator 7. The circulation flow rate of the reaction liquid may be, for example, 0.1 mL/min or more, preferably 0.5 mL/min or more, more preferably 1.0 mL/min or more, and may be, for example, 20 mL/min or less, preferably 18 mL/min or less, more preferably 15 mL/min or less.

The reaction solution may be circulated, for example, once or more, preferably twice or more, more preferably three or more, and may be circulated, for example, 10,000 times or less, preferably 5,000 times or less, more preferably 3,000 times or less.

The present invention will be described in more detail below using examples, but the present invention is not limited to these examples. In the following description, "parts" and "%" expressing amounts are based on mass (weight) unless otherwise specified.

Example 1
<Preparation of Imine Compounds>
Methanol (20 mL) as a solvent, cyclopentanone (6.686 mmol, 592 μL), and 2-aminoethanol (6.647 mmol, 402 μL) were added to a test tube to prepare a reaction solution. The reaction solution was stirred with a touch mixer and then allowed to stand at room temperature for 3 hours to iminize, producing the imine compound cyclopentyl-2-iminoethanol (CPIE) in the reaction solution. The iminization reaction is shown in the following formula.

<Production of amine compounds by hydrogenation reaction>
The reaction liquid containing CPIE was then introduced into a circulating hydrogenation reactor configured as shown in FIG. 1. The test tube used for preparing CPIE was used as the container 1 as it was. A micromixer was used as the fine bubble generator 6. The reaction liquid containing hydrogen fine bubbles (H2-FB) was sent to a catalyst tube (Pd/C NX type 5 wt% (170 mg)) controlled at 60 ° C. by a column oven (CTO-10AC, SHIMAZU) to hydrogenate CPIE, and cyclopentylaminoethanol (CPAE), an amine compound, was produced in the reaction liquid. The hydrogenation reaction is shown in the following formula. The amount of CPAE and CPIE in the sample after the reaction was measured by GC-FID, and the yield and conversion rate were determined. The number of fine bubbles was 5.8 x ¹⁰⁷ .

(Comparative Example 1)
<Preparation of Imine Compounds>
A reaction solution was prepared by adding methanol (5 mL) as a solvent, cyclopentanone (0.49 mmol, 43 μL), and 2-aminoethanol (0.53 mmol, 32 μL) to a stainless steel pressure vessel. The reaction solution was stirred at room temperature for 30 minutes to effect iminization, producing CPIE, an imine compound, in the reaction solution.

<Hydrogenation reaction>
Then, 5 wt% (10.6 mg, 0.5 mol%) of Pd/C NX type was added as a hydrogenation catalyst to the reaction solution containing CPIE. The reaction solution was degassed under reduced pressure, and the stainless steel pressure vessel was introduced into a hydrogenation reaction apparatus configured as shown in FIG. 2 to hydrogenate CPIE, producing CPAE, an amine compound, in the reaction solution. After hydrogen replacement three times, the reaction was carried out at a hydrogen pressure of 0.5 MPa, 1500 rpm, and a reaction temperature of 60°C. The amount of CPAE and CPIE in the sample after the reaction was measured by GC-FID, and the reaction yield was determined. The fine bubbles were 0.6 × 10 ⁷ pieces.

(result)
The results of the Examples and Comparative Examples are shown in Table 1. These results demonstrate that the production method of the present invention makes it possible to hydrogenate organic compounds with a high reaction yield.

The abbreviations in Table 1 have the following meanings.
CPIE: Cyclopentyl-2-iminoethanol F.B.: Fine bubble circulation method

The present invention provides a method for producing an amine compound that can efficiently hydrogenate an imine compound at low pressure.

1 Container 2 Reaction liquid discharge section 3 Pump 4 Hydrogen gas confluence section 5 Heating oven 6 Fine bubble generator (micromixer)
7 Reaction liquid back pressure regulator 8 Hydrogenation reaction vessel (catalyst fixed tube)
9 Reaction liquid recovery section 10 Hydrogen gas supply section 11 Hydrogen gas flow rate regulator

Claims (4)

A method for producing a hydroxyalkylamine compound having a hydrocarbon ring, comprising the steps of: supplying hydrogen fine bubbles having a number of 1.0 x 107 or more bubbles per mL of liquid in a circulation reaction system; and hydrogenating a hydroxyalkylimine ^compound having a hydrocarbon ring in an alcohol solvent using a hydrogenation catalyst ,
The circulation flow rate of the reaction solution is 0.1 mL/min or more and 20 mL/min or less,
The hydrogenation catalyst is
Ziegler catalysts selected from the group consisting of a combination of cobalt acetate and triethylaluminum, a combination of nickel acetylacetonate and triisobutylaluminum, a combination of titanocene dichloride and n-butyllithium, a combination of zirconocene dichloride and sec-butyllithium, and a combination of tetrabutoxytitanate and dimethylmagnesium;
Ruthenium carbene complex catalyst;
Chlorotris(triphenylphosphine)rhodium (Wilkinson's catalyst);
A precious metal complex catalyst comprising a ruthenium compound; or
A catalyst containing a metal selected from the group consisting of nickel, palladium, platinum, rhodium, and ruthenium as an active component.
That is,
Production method . 2. The method according to claim 1, wherein the hydroxyalkylamine compound having a hydrocarbon ring is an aminoethanol compound having a hydrocarbon ring , the hydroxyalkylimine compound having a hydrocarbon ring is an iminoethanol compound having a hydrocarbon ring , and the hydrogenation catalyst is a catalyst containing, as an active component, a metal selected from the group consisting of nickel, palladium, platinum, rhodium and ruthenium. 3. The method according to claim 2, wherein the aminoethanol compound having a hydrocarbon ring is cyclopentylaminoethanol (CPAE), and the iminoethanol having a hydrocarbon ring is cyclopentyl-2-iminoethanol (CPIE). The method according to any one of claims 1 to 3 , wherein the alcohol solvent is methanol .

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