JPWO2016143637A1 - Process for producing primary amines by continuous catalytic reduction of nitriles - Google Patents

Abstract

The present invention provides a novel primary amine production method by catalytic hydrogen reduction of nitriles, which makes it possible to obtain a primary amine with high selectivity and good yield even at a low hydrogen pressure. Let it be an issue. A solution containing a nitrile in which an acid coexists is added to a flow synthesis system having a channel through which a solution is fed and a column filled with an immobilized platinum group metal catalyst in the channel. A method for producing a primary amine, characterized in that the nitriles are continuously catalytically reduced by feeding together with hydrogen having a hydrogen pressure of 1 MPa or less. [Selection figure] None

Description

  The present invention relates to a process for producing a corresponding primary amine with high selectivity and good yield even in low hydrogen pressure in continuous catalytic reduction of nitriles with hydrogen.

As a method for obtaining a primary amine by hydrogen reduction of nitriles, conventionally, an autoclave has been used, and the hydrogen pressure is preferably about 10 MPa and the reaction temperature is preferably about 150 to 200 ° C. However, secondary production of secondary and tertiary amines cannot be avoided by the above method (Non-patent Documents 1, 2, and 3). In response to this problem, a method of adding a basic or acidic substance to the reaction system has been reported.
When ammonia is added as a basic substance and nitriles are reduced at 65 ° C using 2 MPa hydrogen gas in the presence of a nickel aluminum-tungsten alloy as a catalyst, primary amines are obtained in a yield of 90% or more (patented) Reference 1). However, the above method requires a pressure condition of 2 MPa.
In addition, primary amines can be obtained by catalytic hydrogen reduction of nitriles using Pd / C as a catalyst under a hydrogen pressure of 1 MPa or less under acidic conditions, but the yield is low, and there are problems in terms of industrialization. (Patent Documents 2 and 3).
Moreover, in order to suppress the by-production of secondary and tertiary amines, a method for continuously catalytic reduction of nitriles with hydrogen has also been proposed (Patent Document 4). The document deals with high conversion and high selectivity by carrying out continuous catalytic reduction of nitriles in the presence of a hydrogenation catalyst containing one or more metals selected from nickel, cobalt and iron. It is described that a primary amine was obtained. However, the method described in the document still has a problem as an industrial production method such as using a high pressure of 10 MPa and using liquid ammonia as a solvent.

JP 2001-187766 A International Publication No. 2007/002313 Pamphlet International Publication No. 2007/064619 Pamphlet JP 2011-001304 A

Topics in Catalyst, 2010, 53, 979-984 Advanced Synthesis and Catalyst, 2004, 346, 1487-1493 Nishimura Shigeo, Takagi Gen (1987) "Catalytic hydrogenation-Application to organic synthesis" Tokyo Chemical Doujin pp.195-205.

  An object of the present invention is to provide a novel method for producing a primary amine by catalytic hydrogen reduction of nitriles, which makes it possible to obtain a primary amine with high selectivity and good yield even at a low hydrogen pressure. It is to be.

  As a result of intensive research, the inventors of the present invention continuously sent a solution containing nitriles coexisting with an acid together with hydrogen in a flow synthesis system having a column filled with an immobilized platinum group metal catalyst. As a result of catalytic hydrogen reduction, it was found that a primary amine was obtained with high selectivity and good yield even at a low hydrogen pressure of 1 MPa or less, and the present invention was completed. That is, the present invention is characterized by the following.

[1]
A solution containing nitriles coexisting with an acid is added to a flow synthesis system having a flow path through which a solution is sent and a column filled with an immobilized platinum group metal catalyst in the flow path. A method for producing a primary amine, characterized by continuously catalytically reducing the nitriles by feeding together with hydrogen at 1 MPa or less.
[2]
The method for producing a primary amine according to the above [1], wherein the nitrile is an aliphatic nitrile or aromatic nitrile having 2 to 30 carbon atoms.
[3]
Nitriles are acetonitrile, propionitrile, butyronitrile, valeronitrile, decane nitrile, succinonitrile, adiponitrile, benzonitrile, terephthalonitrile, benzyl cyanide, orthochlorobenzyl cyanide, 1,4-bis (2-cyanoethyl) ) Piperazine, N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide, 4-aminobenzonitrile, 2- (trifluoromethyl) benzonitrile, 4-trifluoromethyl-2-methoxybenzonitrile , 2-amino-5-nitrobenzonitrile, 2,5-diaminobenzonitrile, 3- [N- (2-hydroxyethyl) -N-methylamino] propionitrile, cyclohexanecarbonitrile, 1,4-cyclohexanedi Carbonitrile, 2-phenylbenzonitrile, hexanenitrile, 1-cyanonaphthalene, 2-cyanonaphtha The method for producing a primary amine according to the above [2], which is len, 2-cyanopyridine or 2-cyanopyrimidine.
[4]
The method for producing a primary amine according to the above [3], wherein the nitrile is decane nitrile, adiponitrile, benzonitrile or N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide.
[5]
Immobilized platinum group metal catalyst is activated carbon supported palladium catalyst, polydimethylsilane supported palladium catalyst, poly (methylphenyl) silane supported palladium catalyst, polydimethylsilane supported palladium / alumina hybrid catalyst, poly (methylphenyl) silane supported palladium. The method for producing a primary amine according to any one of [1] to [4] above, which is a / alumina hybrid catalyst or a polydimethylsilane-supported palladium / silica hybrid catalyst.
[6]
The method for producing a primary amine according to [5] above, wherein the immobilized platinum group metal catalyst is an activated carbon-supported palladium catalyst, a polydimethylsilane-supported palladium / alumina hybrid catalyst, or a polydimethylsilane-supported palladium / silica hybrid catalyst.
[7]
The method for producing a primary amine according to any one of the above [1] to [6], wherein the acid is hydrochloric acid, trifluoroacetic acid or paratoluenesulfonic acid.
[8]
The method for producing a primary amine according to any one of [1] to [7] above, wherein the hydrogen pressure is 0.1 MPa to 0.3 MPa.

The present invention provides a novel method for producing a primary amine by catalytic hydrogen reduction of a nitrile that makes it possible to obtain a primary amine with high selectivity and good yield even at a low hydrogen pressure. .
The method for producing a primary amine of the present invention uses a low hydrogen pressure of 1 MPa or less, and an industrially used solvent such as a mixed solvent of alcohol and water can be used as a solvent. This is advantageous as a manufacturing method.

  Hereinafter, the present invention will be described in more detail.

The catalyst used in the present invention is an immobilized platinum group metal catalyst.
Examples of the metal species of the catalyst include palladium, platinum, ruthenium, rhodium, iridium and the like, preferably palladium and platinum, and more preferably palladium.
The form of the immobilized catalyst is not particularly limited as long as it can be packed in a column and does not hinder the flow of the reaction solution. However, a polysilane-supported catalyst, an alumina-supported catalyst, a silica-supported catalyst, an activated carbon-supported catalyst, those The catalyst is preferably a polysilane supported catalyst, an alumina supported catalyst, a silica supported catalyst or a hybrid catalyst thereof, more preferably an activated carbon supported catalyst or a polysilane supported / alumina hybrid catalyst.
Examples of the catalyst used in the present invention include activated carbon-supported palladium catalyst, polydimethylsilane-supported palladium catalyst, poly (methylphenyl) silane-supported palladium catalyst, polydimethylsilane-supported palladium / alumina hybrid catalyst (Pd / (PMPSi-Al ₂ O ₃ )), A palladium / alumina hybrid catalyst supported on poly (methylphenyl) silane (Pd / (PSi-Al ₂ O ₃ )) or a palladium / silica hybrid catalyst supported on polydimethylsilane (Pd / (PMPSi-SiO ₂ )), An activated carbon-supported palladium catalyst, a polydimethylsilane-supported palladium / alumina hybrid catalyst (Pd / (PMPSi-Al ₂ O ₃ )) or a polydimethylsilane-supported palladium / silica hybrid catalyst (Pd / (PMPSi-SiO ₂ )) is more preferable.

Hereinafter, an example of each catalyst composition is given.
Pd / (PMPSi-Al ₂ O ₃ ) composition
Pd: 0.5 to 1.2% by mass, preferably 0.6 to 1.1% by mass
C: 3.5 to 4.5% by mass, preferably 3.7 to 4.1% by mass
Al ₂ O ₃ : 75.0 to 95% by mass, preferably 82.0 to 90.0% by mass
SiO ₂ : 6.5 to 10.0% by mass, preferably 7.0 to 9.0% by mass
Pd / (PSi-Al ₂ O ₃ ) composition
Pd: 0.5 to 1.2% by mass, preferably 0.6 to 1.1% by mass
C: 4.2 to 5.2 mass%, preferably 4.5 to 5.0 mass%
Al ₂ O ₃ : 76.0 to 96% by mass, preferably 83.0 to 91.0% by mass
SiO ₂ : 4.0 to 7.0% by mass, preferably 5.0 to 6.0% by mass
Pd / (PMPSi-SiO ₂ ) composition
Pd: 0.5-3 mass%, preferably 0.6-2.5 mass%
C: 2 to 8% by mass, preferably 3 to 5% by mass
SiO ₂ : 89 to 98% by mass, preferably 92 to 96% by mass

  The catalyst efficiency in the catalyst can be evaluated by the catalyst rotation speed, the catalyst rotation frequency, and the like.

Nitriles used in the present invention are aliphatic nitriles or aromatic nitriles having 2 to 30 carbon atoms, and specific examples thereof include acetonitrile, propionitrile, butyronitrile, valeronitrile, decane nitrile, succino nitrile. Nitrile, adiponitrile, benzonitrile, terephthalonitrile, benzyl cyanide, orthochlorobenzyl cyanide, 1,4-bis (2-cyanoethyl) piperazine, N- (2-cyanophenyl) -1,1,1-trifluoromethane Sulfonamide, 4-aminobenzonitrile, 2- (trifluoromethyl) benzonitrile, 4-trifluoromethyl-2-methoxybenzonitrile, 2-amino-5-nitrobenzonitrile, 2,5-diaminobenzonitrile, 3 -[N- (2-hydroxyethyl) -N-methylamino] propionitrile, cyclohexanecarbonitrile, 1,4-cycl Examples include rhohexanedicarbonitrile, 2-phenylbenzonitrile, hexanenitrile, 1-cyanonaphthalene, 2-cyanonaphthalene, 2-cyanopyridine, 2-cyanopyrimidine, and preferably decanenitrile, adiponitrile, benzonitrile or N -(2-Cyanophenyl) -1,1,1-trifluoromethanesulfonamide.
The nitriles in the present invention may have a plurality of nitrile groups in the molecule. The number of nitrile groups is preferably 1 to 5, more preferably 1 to 3, and even more preferably 1 or 2.

  The primary amine obtained by the method of the present invention is a primary amine corresponding to the above nitriles.

The solution containing the nitrile in which the acid used in the present invention coexists may contain a solvent.
The solvent is not particularly limited as long as it does not inhibit the progress of the reaction. For example, aromatic hydrocarbon solvents such as toluene and o-xylene, and aliphatic hydrocarbon solvents such as hexane, heptane and petroleum ether. , Alicyclic hydrocarbon solvents such as cyclohexane, aromatic halogenated hydrocarbon solvents such as chlorobenzene and o-dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,1-trichloroethane , Aliphatic halogenated hydrocarbon solvents such as trichloroethylene and tetrachloroethylene, ether solvents such as diethyl ether, diisopropyl ether, 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane, cyclopentyl methyl ether, triethylamine, tributylamine, N, N- Amine solvents such as methylaniline, pyridine solvents such as pyridine and picoline, ester solvents such as ethyl acetate, n-butyl acetate, ethyl propionate, propylene glycol-1-monomethyl ether-2-acetate, methanol, ethanol, alcohol solvents such as n-propanol, 2-propanol, ethylene glycol, propylene glycol-1-monomethyl ether, ketone solvents such as acetone and methyl isobutyl ketone, carbonate solvents such as dimethyl carbonate and diethyl carbonate, dimethyl sulfoxide, Examples include sulfolane, 1,3-dimethyl-2-imidazolidinone, ethylene glycol diacetate, acetic acid, and water.
Preferred is methanol, ethanol, propanol, toluene, water or tetrahydrofuran, and more preferred is methanol, ethanol, propanol or water. These solvents may be used as a mixture of two or more.

  The concentration of nitriles as a substrate is not particularly defined as long as it does not interfere with the flow to the column, but is preferably 0.1% by mass to 100% by mass, more preferably 1% by mass to 80% by mass, and more preferably 10% by mass to 50% by mass. % Is more preferable.

Acids that coexist with nitriles include inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid, carboxylic acids such as acetic acid, formic acid, trifluoroacetic acid, and oxalic acid, methanesulfonic acid, paratoluenesulfonic acid, and trifluoromethanesulfonic acid. Examples of the sulfonic acids include, but are preferably hydrochloric acid, sulfuric acid, acetic acid, formic acid, trifluoroacetic acid, paratoluenesulfonic acid or methanesulfonic acid, and more preferably hydrochloric acid, trifluoroacetic acid, or paratoluenesulfonic acid. . These acids may be used as a mixture of two or more.
The amount of the acid to be used is 1 to 10 mol times, preferably 1 to 3 mol times, more preferably 1.2 to 2 mol, relative to 1 mol of the nitrile group and basic site contained in the substrate. Double the amount.
The acid may be mixed in advance with the substrate solution, or may be continuously mixed in the flow path before the column.

The pressure of hydrogen introduced into the reaction field in the present invention, that is, the hydrogen pressure is not particularly defined as long as the reaction proceeds, but is specifically 0.01 MPa to 1 MPa, preferably 0.1 MPa to 1 MPa. More preferably, it is 0.1 MPa to 0.3 MPa. “MPa” is a unit of pressure and means megapascal.
Note that hydrogen can be used by mixing with an inert gas such as nitrogen, helium, or argon. In this case, the hydrogen pressure means a partial pressure of hydrogen in the mixed gas.

  Although there is no restriction | limiting in particular in reaction temperature, It is 0 to 150 degreeC specifically, Preferably it is 15 to 100 degreeC, More preferably, it is 30 to 80 degreeC.

  The flow synthesis system in the present invention means a system that uses a reaction vessel having an inlet and an outlet and simultaneously performs “feeding of raw materials from the inlet”, “reaction” and “recovering the product from the outlet”. The concept is well known to those skilled in the art (for example, “Flow Micro Synthesis” (Chemical Doujinshi), 2014, page 9). In the flow synthesis system of the present invention, the reaction vessel has a thin tubular shape, preferably a column shape.

Although the material of the column which concerns on this invention is not specifically limited, As a specific example, glass, stainless steel (SUS), Hastelloy, and Teflon (trademark) are mentioned. Examples of the continuous contact reaction column include the following combinations.
Pd / (PMPSi-Al ₂ O ₃ ) 1.8 g is packed in a column with an outer diameter of 8 mm, a wall thickness of 1.6 mm (inner diameter of 4.8 mm), and a length of 110 mm until the catalyst length reaches 100 mm. Prepare a close packed packing of / (PMPSi-Al ₂ O ₃ ) 0.94 g in a glass column with an outer diameter of 11 mm, a wall thickness of 2.2 mm (inner diameter of 6.6 mm), and a length of 30 mm.

  The tube used for introducing and discharging the substrate to and from the catalyst column is not particularly limited, and a specific example is a Teflon tube having an inner diameter of 1 mm.

  A back pressure may be applied to the flow path after passing through the column using a back pressure valve or the like. The range of the back pressure is 0 MPa to 1 MPa, preferably 0 MPa to 0.5 MPa, more preferably 0 MPa to 0.3 MPa.

Next, the present invention will be described in more detail with reference to examples. The scope of the present invention is not limited to the following examples.
In the examples, “(v / v)” means (volume / volume), “M” means mol / L, and “normal pressure” means 0.1 MPa.
The proton nuclear magnetic resonance ( ¹ H NMR) chemical shift values of the examples were measured in a heavy solvent using ECX-600, ECA-500 or JNM-ECP300 manufactured by JEOL (JEOL). It was shown as a δ value (ppm) when methylsilane was used as an internal standard (0.0 ppm).
In description of NMR spectrum, “s” is singlet, “t” is triplet, “m” is multiplet, “br” is broad, “J” is coupling constant, “Hz” is Hertz, “CD ₃ OD” Represents deuterated methanol, and “DMSO-d ₆ ” represents deuterated dimethyl sulfoxide.
In the examples, “Quant.” Is quantitative, “trace” is trace, “Conv.” Is conversion, “CF ₃ COOH” is trifluoroacetic acid, and “p-TsOH” is p-toluenesulfonic acid. To do.

Example 1: Synthesis of 1-decanamine hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) was packed into a 5φ × 100 mm diameter SUS column. While maintaining the column temperature at 60 ° C with an aluminum block, 6 mL of ethanol / water = 4/1 (v / v) solution of decane nitrile (0.153 mg, 1 mmol) containing hydrochloric acid equivalent to 0.3 M Pressure hydrogen gas was gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the decane nitrile solution to the micromixer was maintained at 100 μL / min, and the supply rate of hydrogen gas was maintained at 10 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor and collected for 1 hour. The solvent was distilled off from the reaction solution thus obtained under reduced pressure to quantitatively obtain 194 mg of 1-decanamine hydrochloride as a brown powder.
¹ H NMR (500 MHz, CD ₃ OD): δ5.26-5.22 (m, 2H), 5.23 (s, 2H), 2.88 (t, 2H, J = 7.7 Hz), 1.68-1.62 (m, 2H) , 1.39-1.29 (m, 14H), 0.89 (t, 3H, J = 6.5 Hz)

Example 2: Synthesis of 1-decanamine hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) in a 4.8φ × 100 mm diameter glass column Packing and maintaining the column temperature at 80 ° C with an aluminum block, decane nitrile (0.153 mg, 1 mmol) in 1-propanol / water = 4/1 (v / v) solution containing hydrochloric acid equivalent to 0.3 M 6 mL and normal-pressure hydrogen gas were gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the decane nitrile solution to the micromixer was maintained at 100 μL / min, and the supply rate of hydrogen gas was maintained at 10 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor and collected for 60 minutes. The solvent was distilled off from the reaction solution thus obtained under reduced pressure to quantitatively obtain 194 mg of 1-decanamine hydrochloride as a white powder.
¹ H NMR (500 MHz, CD ₃ OD): δ5.26-5.22 (m, 2H), 5.23 (s, 2H), 2.88 (t, 2H, J = 7.7 Hz), 1.68-1.62 (m, 2H) , 1.39-1.29 (m, 14H), 0.89 (t, 3H, J = 6.5 Hz)

Example 3: Synthesis of 1,6-diaminohexane dihydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) in a 4.8φ × 100 mm diameter glass column With 9 ml of ethanol / water = 4/1 (v / v) solution of adiponitrile (108 mg, 1 mmol) containing hydrochloric acid equivalent to 0.3 M, with the column temperature kept at 75 ° C. with an aluminum block, Normal pressure hydrogen gas was gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the adiponitrile solution to the micromixer was maintained at 100 μL / min, and the supply rate of hydrogen gas was maintained at 10 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor and collected for 90 minutes. The solvent was distilled off from the reaction solution thus obtained under reduced pressure to quantitatively obtain 189 mg of 1,6-diaminohexane dihydrochloride as a white powder.
¹ H NMR (500 MHz, CD ₃ OD): δ5.16 (s, 4H), 2.78 (t, 4H, J = 7.4 Hz), 1.57-1.63 (m, 4H), 1.38-1.41 (m, 4H)

Example 4: Synthesis of benzylamine hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) in a 4.8φ × 100 mm diameter glass column With 6 mL of ethanol / water = 4/1 (v / v) solution of benzonitrile (124 mg, 1.2 mmol) containing hydrochloric acid equivalent to 0.3 M in a packed and column temperature maintained at 30 ° C with an aluminum block Then, normal-pressure hydrogen gas was gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the benzonitrile solution to the micromixer was maintained at 200 μL / min, and the supply rate of hydrogen gas was maintained at 10 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor and collected for 30 minutes. The solvent was distilled off from the reaction solution thus obtained under reduced pressure. The reduction reaction proceeded quantitatively to obtain 172 mg of benzylamine hydrochloride.
¹ H NMR (500 MHz, CD ₃ OD): δ 7.49-7.39 (m, 5H), 4.91 (s, 3H), 4.12 (s, 2H)

Example 5: Continuous synthesis of benzylamine hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) in a 4.8φ × 100 mm diameter glass column While the column temperature was kept at 30 ° C with an aluminum block, 96 mL of ethanol / water = 4/1 (v / v) solution of benzonitrile (1.98 g, 19.2 mmol) containing hydrochloric acid equivalent to 0.3 M was added. Then, normal pressure hydrogen gas was gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the benzonitrile solution to the micromixer was maintained at 200 μL / min, and the supply rate of hydrogen gas was maintained at 10 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor and collected for 8 hours. The solvent was distilled off from the reaction solution thus obtained under reduced pressure. The reduction reaction proceeded quantitatively to obtain 2.76 g of benzylamine hydrochloride.
¹ H NMR (500 MHz, CD ₃ OD): δ 7.49-7.39 (m, 5H), 4.91 (s, 3H), 4.12 (s, 2H)

Reference Example 1: Synthesis of benzylamine hydrochloride (batch reaction)
In a flask, 96 mL of ethanol / water = 4/1 (v / v) solution of benzonitrile (1.98 g, 19.2 mmol) containing hydrochloric acid equivalent to 0.3 M and Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g , Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100), and kept at 30 ° C. while stirring under normal pressure hydrogen gas. At this time, the supply rate of hydrogen gas was kept at 10 mL / min. After 8 hours, the catalyst was removed by filtration, and the solvent was distilled off from the reaction solution and unreacted raw material under reduced pressure to obtain the desired benzylamine hydrochloride, dibenzylamine hydrochloride, tribenzylamine hydrochloride and cyclohexanemethyl. A mixture of amine hydrochlorides was obtained in 146.6 mg (5% yield) (benzylamine hydrochloride / dibenzylamine hydrochloride / tribenzylamine hydrochloride / cyclohexanemethylamine hydrochloride = 41/19/27/13) . These ratios were determined by analyzing the alkali-treated sample by gas chromatography with an FID detector.
<GC analysis conditions>
Column: Agilent capillary column HP-5MS UI (0.18mmx20m, 0.18μm), injection temperature: 270 ° C, FID detector temperature: 270 ° C, gas used: helium, flow rate: 50cm / s, oven temperature: 50 ° C (2 Min), 20 ° C / min temperature rise, 250 ° C (1 min)
Retention time: PhCN (4.12 minutes), benzylamine (4.32 minutes), dibenzylamine (9.33 minutes), tribenzylamine (12.10 minutes), cyclohexanemethylamine (3.95 minutes)

Example 6: Continuous synthesis of N- [2- (aminomethyl) phenyl] -1,1,1-trifluoromethanesulfonamide hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (0.94 g, Pd: 56 μmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-60) is packed in a 6.6φ × 30 mm diameter glass column. In the state where the column temperature was kept at 50 ° C. with an aluminum block, methanol / water of raw material N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide containing hydrochloric acid equivalent to 60 mM = 4 / 1 (v / v) A 40 mM solution and hydrogen gas were gradually mixed using a micromixer. At this time, the supply rate of the substrate solution was maintained at 100 μL / min using a plunger pump, and the supply rate of hydrogen gas was maintained at 10 mL (converted to the standard state) / min using a mass flow controller. A Teflon tube having an inner diameter of 1 mm and a back pressure valve of 40 psi (about 0.28 MPa) were connected to the outlet of the reactor and collected for 5 hours. When the reaction solution thus obtained was analyzed by LC, N- [2- (aminomethyl) phenyl] -1,1,1-trifluoromethanesulfonamide was obtained with an area percentage of 99%.
<LC analysis conditions>
Column: Inertsil Ph-3 (4.6x50 mm, 3 um)
Oven temperature: 45 ℃
Flow rate: 1.0 mL / min
Eluent; MeCN / 0.1% AcOHaq = 15/85 (19 min) -85/15 (24 min)
Detection wavelength: UV @ 220nm
Retention time: N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide 2.97 minutes, N- [2- (aminomethyl) phenyl] -1,1,1-trifluoromethanesulfonamide 6.20 minutes
¹ H NMR (300 MHz, DMSO-d ₆ ): δ8.2-7.7 (br, 2H), 7.33 (d, 1H), 7.1-7.2 (m, 2H), 6.81 (t, 1H), 3.8-4.0 (m, 2H)

Example 7: 100-hour continuous synthesis of benzylamine hydrochloride 300 μL / min of ethanol / water = 4/1 (v / v) solution of benzonitrile and hydrochloric acid (prepared so that the concentrations are 1.0M and 1.5M, respectively) After mixing with 67 mL / min of hydrogen through a micromixer, Pd / (PMPSi-Al ₂ O ₃ ) (Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals, Inc., trade name: polysilane supported catalyst PPD- 100) was passed through a glass column with a diameter of 4.8φ × 100 mm packed with 1.8 g. At this time, the column was kept at 60 ° C with an aluminum block. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the column.
When continuous operation was performed for 100 hours in this state, even after 100 hours of circulation, the reaction proceeded quantitatively in the same manner as in the initial stage of circulation, and no deactivation of the catalyst was observed. The palladium concentration in the effluent was <2 ppb (below the detection limit). The catalyst rotation frequency (TOF) was 100 / h, and the catalyst rotation speed (TON) at the time of 100 hours flow was 10,000.

Example 8: Synthesis of benzylamine hydrochloride Palladium catalyst supported on activated carbon (5% Pd / C, 0.38 g) was packed in a glass column with a diameter of 4.8φ × 100 mm, and the column temperature was maintained at 60 ° C. with an aluminum block. In this state, 1.0 M benzonitrile in 1-propanol / water = 4/1 (v / v) containing 1.5 M hydrochloric acid and hydrogen gas were gradually mixed using a micromixer. The supply rate of the benzonitrile solution was maintained at 200 μL / min, and the supply rate of hydrogen gas was maintained at 45 mL / min (standard condition conversion). The hydrogen pressure was 870-890 kPa. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor, and the effluent was collected. When the reaction solution thus obtained was treated with an alkali and analyzed by gas chromatography, benzylamine was quantitatively obtained, and dibenzylamine, tribenzylamine, and cyclohexanemethylamine were not detected (analysis conditions were Same as Reference Example 1). In addition, the outflow of palladium was not confirmed.

Example 9: Synthesis of benzylamine hydrochloride
Pd / (PMPSi-Al ₂ O ₃ ) (1.8 g, Pd: 0.1 mmol / g, manufactured by JGC Catalysts & Chemicals Co., Ltd., trade name: polysilane-supported catalyst PPD-100) in a 4.8φ × 100 mm diameter glass column Packing and maintaining the column temperature at 60 ° C. with an aluminum block, a 1-propanol / water = 4/1 (v / v) solution of benzonitrile (1.98 g, 19.2 mmol) containing 0.3 M equivalent of acid 96 mL and hydrogen gas of about 200 kPa were gradually mixed using a micromixer. At this time, using a syringe pump, the supply rate of the benzonitrile solution to the micromixer was maintained at 300 μL / min, and the supply rate of hydrogen gas was maintained at 13.4 mL / min. A Teflon tube having an inner diameter of 1 mm was connected to the outlet of the reactor, and the effluent was collected. The reaction solution thus obtained was treated with an alkali and analyzed by gas chromatography. The results shown in Table 1 were obtained (analysis conditions were the same as in Reference Example 1).

Example 10: Continuous synthesis of benzylamine hydrochloride
2.4% Pd / (PMPSi-SiO ₂ ) (0.55 g, polydimethylsilane-supported palladium / silica hybrid catalyst manufactured by JGC Catalysts & Chemicals Co., Ltd.) was packed in a glass column with a diameter of 6.6φ × 25 mm, and the column temperature was changed to aluminum block With a micromixer, gradually mix ethanol / water = 85/15 (v / v) 0.2M solution of raw material benzonitrile containing hydrochloric acid equivalent to 0.3M and hydrogen gas in a state maintained at 100 ° C. did. At this time, the supply rate of the substrate solution was maintained at 0.5 mL / min using a syringe pump, and the supply rate of hydrogen gas was maintained at 24 mL (converted to the standard state) / min using a mass flow controller. A Teflon tube having an inner diameter of 1 mm and a back pressure valve of 40 psi (about 0.28 MPa) were connected to the outlet of the reactor, and the solution was continuously fed for 10 minutes. The reaction solution thus obtained was treated with alkali and analyzed by GC with a FID detector. As a result, benzylamine was obtained in an area percentage of 95%. Dibenzylamine was not detected (analysis conditions were the same as in Reference Example 1).

Example 11: Continuous synthesis of benzylamine hydrochloride
0.5% Pd / SC (1.15 g (moisture content: 32.78%), palladium catalyst supported on spherical activated carbon manufactured by NU Chem Cat Co., Ltd.) was packed into a glass column of 6.6φ × 35 mm diameter, and the column temperature was adjusted to 100 ° C with an aluminum block. In this state, a raw material benzonitrile ethanol / water = 85/15 (v / v) 0.2 M solution containing 0.3 M hydrochloric acid and hydrogen gas were gradually mixed using a micromixer. At this time, the supply rate of the substrate solution was maintained at 0.25 mL / min using a plunger pump, and the supply rate of hydrogen gas was maintained at 12 mL (standard state conversion) / min using a mass flow controller. A Teflon tube having an inner diameter of 1 mm and a back pressure valve of 40 psi (about 0.28 MPa) were connected to the outlet of the reactor, and the solution was continuously fed for 15 minutes. The reaction solution thus obtained was treated with alkali and analyzed by GC with a FID detector. As a result, benzylamine was obtained in an area percentage of 89%. Dibenzylamine was not detected (analysis conditions were the same as in Reference Example 1).

  The method for producing a primary amine of the present invention is useful in that a primary amine can be produced from nitriles with high selectivity and good yield without requiring a high-pressure reaction facility.

Claims (8)

  A solution containing nitriles coexisting with an acid is added to a flow synthesis system having a flow path through which a solution is sent and a column filled with an immobilized platinum group metal catalyst in the flow path. A method for producing a primary amine, characterized by continuously catalytically reducing the nitriles by feeding together with hydrogen at 1 MPa or less.   The method for producing a primary amine according to claim 1, wherein the nitrile is an aliphatic nitrile or aromatic nitrile having 2 to 30 carbon atoms.   Nitriles are acetonitrile, propionitrile, butyronitrile, valeronitrile, decane nitrile, succinonitrile, adiponitrile, benzonitrile, terephthalonitrile, benzyl cyanide, orthochlorobenzyl cyanide, 1,4-bis (2-cyanoethyl) ) Piperazine, N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide, 4-aminobenzonitrile, 2- (trifluoromethyl) benzonitrile, 4-trifluoromethyl-2-methoxybenzonitrile , 2-amino-5-nitrobenzonitrile, 2,5-diaminobenzonitrile, 3- [N- (2-hydroxyethyl) -N-methylamino] propionitrile, cyclohexanecarbonitrile, 1,4-cyclohexanedi Carbonitrile, 2-phenylbenzonitrile, hexanenitrile, 1-cyanonaphthalene, 2-cyanonaphtha The manufacturing method of the primary amine of Claim 2 which is a len, 2-cyano pyridine, or 2-cyano pyrimidine.   The method for producing a primary amine according to claim 3, wherein the nitrile is decane nitrile, adiponitrile, benzonitrile or N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide.   Immobilized platinum group metal catalyst is activated carbon supported palladium catalyst, polydimethylsilane supported palladium catalyst, poly (methylphenyl) silane supported palladium catalyst, polydimethylsilane supported palladium / alumina hybrid catalyst, poly (methylphenyl) silane supported palladium. The method for producing a primary amine according to any one of claims 1 to 4, which is a / alumina hybrid catalyst or a polydimethylsilane-supported palladium / silica hybrid catalyst.   The method for producing a primary amine according to claim 5, wherein the immobilized platinum group metal catalyst is an activated carbon-supported palladium catalyst, a polydimethylsilane-supported palladium / alumina hybrid catalyst, or a polydimethylsilane-supported palladium / silica hybrid catalyst.   The method for producing a primary amine according to any one of claims 1 to 6, wherein the acid is hydrochloric acid, trifluoroacetic acid or paratoluenesulfonic acid.   The method for producing a primary amine according to any one of claims 1 to 7, wherein the hydrogen pressure is 0.1 MPa to 0.3 MPa.