JP5197320B2 - Method for producing α-aminoketone compound - Google Patents

Description

  The present invention relates to a method for producing an α-aminoketone compound in which a polyhydric alcohol and a secondary amine compound are reacted.

  As a method for producing an α-aminoketone compound, a reaction between 2-haloketones and an amine is known, but the yield is generally low (for example, Patent Document 1 and Non-Patent Document 1). Thus, various techniques have been developed to suppress side reactions and improve yield. Patent Document 2 discloses a method of reacting by using a mixed solvent of water and alcohol and adjusting the molar ratio of 2-haloketone and amine in the solvent. Patent Document 3 discloses that the reaction can be suppressed and the yield can be improved by reacting at a low temperature of −30 ° C. to less than the boiling point of the solvent in various organic solvents excluding the alcohol solvent.

  On the other hand, a method for producing an α-aminoketone compound without using 2-haloketones as a starting material has also been developed. In Patent Document 4, desorption bonded to an organic sulfide and a primary or secondary carbon atom. By reacting a sulfonium salt formed by reacting a free radical having a group (benzyl halide) with a ketone, and forming α-aminoalcohol from the reaction of the obtained oxirane and amine, followed by selective oxidation. , A method for producing an α-aminoketone is disclosed.

  Also known are alcohol-based amine production methods in which an amino compound is produced using a metal catalyst using alcohol and amine as starting materials, and among them, a plurality of examples using polyhydric alcohols as raw materials have been reported. For example, Patent Document 5 discloses a method of obtaining an amino alcohol by reacting a polyhydric alcohol and ammonia using a nickel catalyst modified with a compound containing a specific element. Patent Document 6 discloses a hydrogenation catalyst impregnated with a solvent and a method of aminating an alcohol in the gas phase in the presence of hydrogen. In Patent Document 7, a method of reacting a polyhydric alcohol with ammonia, a primary amine, or a secondary amine using a catalyst subjected to a specific treatment containing copper, nickel, calcium, alkali metal, or alkaline earth metal. It is disclosed.

JP 60-120845 A JP-A-63-192744 International Publication No. 2003/91200 Pamphlet Special table 2008-505865 gazette JP-A-1-242559 Japanese Patent Laid-Open No. 9-20735 JP 2008-44930 A J. et al. Am. Chem. Soc. 1928, 50, 2290

However, in the method of Patent Document 1, hydrogen halide or a neutralized salt thereof is by-produced in an equimolar amount during the reaction, which places a high load on the environment and is not clean. Moreover, since the method of patent document 2 is a multistage reaction, it is industrially disadvantageous from the viewpoint of capital investment, running cost, and waste disposal, and has a large load on the environment.
The methods shown in Patent Documents 6 and 7 are only carried out with terminal diols, and there are no examples of reactions in trihydric or higher polyhydric alcohols that are more polar and difficult to control. In Patent Document 5, a reaction example using glycerin is reported, but it is difficult to say that both the conversion rate and the selectivity have reached sufficient levels, and the results are not sufficiently satisfactory industrially.
As described above, there is no known example in which an α-aminoketone compound is selectively synthesized by an alcohol-based amine production method using a trihydric or higher polyhydric alcohol as a raw material. There are problems such as that it takes a long time to complete the process and that a large amount of by-products are generated, and the target product cannot be produced with high yield and good selectivity.
Accordingly, an object of the present invention is to provide a method for efficiently and selectively producing an α-aminoketone compound in a high yield using a trihydric or higher polyhydric alcohol.

The present inventors have found that the above problem can be solved by reacting a trihydric or higher polyhydric alcohol with a secondary amine compound in the presence of a catalyst containing a specific metal.
That is, the present invention provides a trihydric or higher polyhydric alcohol (B) and a second alcohol in the presence of a catalyst (A) containing one or more metal components selected from the group consisting of copper, nickel, ruthenium, aluminum and iron. Provided is a method for producing an α-aminoketone compound by reacting with a secondary amine compound (C).

  According to the present invention, an α-aminoketone compound can be produced from a polyhydric alcohol as a starting material selectively and efficiently in one step, and further with little by-products and a high yield.

[Catalyst (A)]
In the production method of the present invention, the catalyst (A) used contains at least one metal component selected from copper, nickel, ruthenium, aluminum and iron as a main active metal component, and copper is essential. Are preferable in terms of activity, selectivity, and economy. One or more kinds of metal components different from the main active metal component may be included as the catalyst active assistant component or composite component.
Examples of the activity auxiliary component and composite component of the catalyst include palladium, platinum, rhodium, rhenium, iridium, molybdenum, cobalt, chromium, manganese, zinc, yttrium, vanadium, and zirconium.
The shape of the catalyst (A) can be prepared and used as needed, such as a Raney type, a support type, a colloidal type, etc., and may be used in a powder form or molded.

As a support for improving physical factors such as the durability of the catalyst, or as a support for supporting at least one metal component selected from, for example, copper, nickel, ruthenium, aluminum and iron when molding, for example, , Studies in Surface and Catalysis, 1-25, vol 51, 1989, and the like can be used. Specifically, composite oxides of silica-alumina such as carbon (activated carbon), diatomaceous earth, clay, alumina, silica, titania, zirconia, ceria, and zeolite can be used. Of these, silica, alumina, carbon and silica-alumina composite oxides are particularly preferred.
The supported amount of the metal component is usually preferably about 0.10 to 70% by mass, more preferably 1 to 55% by mass based on the total amount of the carrier and the supported metal component from the viewpoint of catalytic activity. .
As the catalyst (A) carrying a metal component, a commercially available one may be used, or a commonly used method such as precipitation, ion exchange, evaporation to dryness, spray drying or kneading. It can be prepared by loading a metal component on a carrier.

In the production method of the present invention, the catalyst (A) to be used may be separately reduced with hydrogen gas and another reducing agent, while circulating hydrogen in a high boiling point solvent such as higher alcohol or liquid paraffin, Or you may use what was separated by filtration after carrying out reduction processing, introducing other reducing agents continuously.
Further, the polyhydric alcohol and secondary amine compound as raw materials are put together with the catalyst into the reactor without introducing a reduction treatment in advance, and hydrogen gas is introduced, or the secondary amine compound to be reacted is gaseous. In some cases, a reduction treatment can be performed by raising the temperature to the reaction temperature and the temperature leading to reduction while introducing a mixed gas of hydrogen gas and gaseous amine.
In addition, it does not interfere with the reduction treatment and may be used for the reaction as it is.

The amount of the metal component used in the catalyst is appropriately determined according to the type of polyhydric alcohol, but in the case of batch reaction, from the viewpoint of conversion rate and selectivity, As a metal, 0.0001 g or more is preferable, More preferably, it is 0.001-0.5 g, More preferably, it is the range of 0.01-0.2 g.
In the production method of the present invention, the catalyst can be charged in an arbitrary amount. However, in the case of a batch reaction, from the viewpoint of reactivity, selectivity and economy, the amount of the catalyst is 0. 5-50 mass% is preferable, More preferably, it is 1-20 mass%, More preferably, it is 4-10 mass%.

[Trihydric or higher polyhydric alcohol (B)]
The trihydric or higher polyhydric alcohol (B) used in the present invention is preferably a glycerin or a compound having a glycerin structure at the end, that is, a polyhydric alcohol represented by the following formula (I). . Moreover, it is preferable that the total carbon number of polyhydric alcohol (B) more than trivalence is 3-50, and it is more preferable that it is 3-25.
The α-aminoketone compound is obtained by the reaction of the glycerin structure with the secondary amine.

In the formula (I), R ¹ is a hydrogen atom or a hydrocarbon group in which part or all of the hydrogen atoms are a hydroxyl group or a hydrogen atom of a hydroxyl group is substituted with a substituent. Examples of the substituent include, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group, neopentyl group, benzyl group, p-methoxyphenylbenzyl group, methoxymethyl group, and trimethylsilyl group. , Triethylsilyl group, triisopropylsilyl group, t-butyldimethylsilyl group, t-butyldiphenylsilyl group, tosyl group, acetyl group, benzoyl group and trityl group. 1-47 are preferable and, as for carbon number of a hydrocarbon group, 1-22 is more preferable. Further, the number of hydroxyl groups of R ¹ is preferably 10 or less, and more preferably 5 or less.

  Examples of the polyhydric alcohol represented by the formula (I) include glycerin, 1,2,3-butanetriol, 1,2,3-pentanetriol, 1,2,3-hexanetriol, 1,2,3. -Heptanetriol, 1,2,3-octanetriol, 1,2,3-nonanetriol, 1,2,3-decanetriol, 1,2,3-undecantriol, 1,2,3-dodecantriol, 1 , 2,3-tridecanetriol, 1,2,3-tetradecanetriol, 1,2,3-pentadecanetriol, 1,2,3-hexadecanetriol, 1,2,3-heptadecanetriol, 1,2, 3-octadecanetriol, 1,2,3-nonadecanetriol, 1,2,3-icosantriol, 1,2,3,5-pentanetetraol, 5 Aliphatic polyhydric alcohols such as methoxy-1,2,3-pentanetriol and related compounds, erythritol, threitol, ribitol, arabinitol, xylitol, allitol, sorbitol, mannitol, iditol, galactitol, taritol, boleitol, perseitol, etc. And various sugar alcohols thereof and related compounds thereof. Among these polyhydric alcohols, glycerin or aliphatic polyhydric alcohols and related compounds are preferable, and glycerin is particularly preferable.

[Secondary amine compound (C)]
The secondary amine compound (C) used as a starting material in the present invention is preferably a compound that can be represented by the following formula (II).

In the formula (II), R ² and R ³ are each a hydrocarbon group which may be substituted with a substituent, and are bonded to each other directly or through a hetero atom (O, N, S, etc.). A ring structure may be formed, and the mode of bonding may be saturated or unsaturated. As the substituent, for example, a hydroxyl group or a hydrogen atom of a hydroxyl group is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a neopentyl group, a benzyl group, or a p-methoxyphenylbenzyl group. , Methoxymethyl group, trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, t-butyldimethylsilyl group, t-butyldiphenylsilyl group, tosyl group, acetyl group, benzoyl group and trityl group, A dialkylamino group etc. are mentioned. 1-40 are preferable and, as for carbon number of a hydrocarbon group, 1-20 are more preferable.

  Examples of the secondary amine compound represented by the formula (II) include dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, dihexylamine, diheptylamine, dioctylamine, dinonylamine, didecylamine, diundecylamine. , Didodecylamine, ditridecylamine, ditetradecylamine, dipentadecylamine, dihexadecylamine, diheptadecylamine, dioctadecylamine, methylethylamine, methylpropylamine, ethylpropylamine, methylbutylamine, methylpentylamine Dialkylamines such as methylhexylamine, methylheptylamine, methyloctylamine, methyldodecylamine, methylstearylamine and related compounds, diphenylamine Diarylamines such as dibenzylamine, methylphenylamine, ethylphenylamine, methylbenzylamine, ethylbenzylamine and related compounds, arylalkylamines and related compounds, cyclic amines such as morpholine, pyrrolidine, piperazine, isoindoline and the like Amino acids having a secondary amino group such as an analogous compound and proline, and analogues thereof.

In the production method of the present invention, the charged amount of the secondary amine compound (C) with respect to the trihydric or higher polyhydric alcohol (B) is preferably 0 in terms of molarity from the viewpoint of the reactivity and the yield of the target product. 0.7 equivalent or more is preferable, and 0.8 equivalent or more is more preferable. Further, from the viewpoint of disproportionation of the amine compound and suppression of side reactions, it is preferably 20 equivalents or less, more preferably 10 equivalents or less in terms of mole.
Further, the secondary amine compound (C) may be added continuously, charged from the beginning, or divided into a certain amount and appropriately introduced into the reaction system, and the introduction method is not particularly limited.

[Reaction conditions]
In the production method of the present invention, it is preferable to introduce the reducing gas and / or the inert gas into the reaction system, for example, intermittently or continuously. By introducing and circulating the gas, water produced by the reaction between the trihydric or higher polyhydric alcohol (B) and the secondary amine compound (C) is introduced into the gas phase as reactive water vapor, and the outside of the reaction system. The reaction can be promoted by this. In this case, hydrogen can usually be used as the reducing gas, and nitrogen, argon, or the like can usually be used as the inert gas. These reducing gases and inert gases can be used alone or in combination.
The introduction and flow of the gas may be performed continuously or continuously, and the by-produced water may be appropriately removed without being present in the reaction system for a long time. It is desirable to remove them automatically. Specifically, it is common to introduce an appropriate amount of inert gas and / or reducing gas into the reaction system during the reaction and distill water out of the reaction system together with the inert gas and / or reducing gas. It is. The circulating gas can be reused by concentrating and separating the water produced as a by-product in the condenser, and the water removal technique is not limited to that described.

In the production method of the present invention, the reaction temperature may be appropriately determined depending on the type of the catalyst (A), the trivalent or higher polyhydric alcohol (B), and the secondary amine compound (C). 100 to 350 ° C. when the polyhydric alcohol (B) is glycerin, 1,2,3-butanetriol or erythritol and the secondary amine compound (C) is dimethylamine, diethylamine, dihexylamine or didecylamine Is preferable, 150-250 degreeC is more preferable, and 170-230 degreeC is further more preferable.
If it is 100 ° C. or higher, sufficient catalytic activity can be exhibited, and if it is 350 ° C. or lower, trivalent or higher polyhydric alcohol (B), secondary amine compound (C), and decomposition or overreaction of the product. It is preferable in terms of suppression.

  In the production method of the present invention, the reaction pressure is not particularly limited, but is appropriately determined in consideration of the type of the catalyst (A), the trihydric or higher polyhydric alcohol (B), the secondary amine compound (C), and the reaction temperature. Can be determined. When the reaction is carried out batchwise, water tends to remain in the system, so it is preferable to reduce the moisture in the reaction by introducing and circulating a gas. The gas pressure is, for example, a trihydric or higher polyhydric alcohol. In the case where (B) is glycerin, 1,2,3-butanetriol or erythritol and the secondary amine compound (C) is dimethylamine, diethylamine, dihexylamine or didecylamine, it is more preferable from the viewpoint of industrialization. 001-30 MPa is preferable, 0.01-15 MPa is more preferable, and 0.1-5 MPa is further more preferable. If it is 30 Mpa or less, the target product can be obtained with high yield and high selectivity.

  Hereinafter, the conversion of the polyhydric alcohol and the production confirmation and yield determination of the α-aminoketone compound were performed using gas chromatography (GC) and gas chromatography / mass spectrometry (GC / MS).

Example 1
A 500 mL separable flask equipped with a condenser and a separator for separating the produced water, a reaction mixture sampling device, an exhaust gas outlet tube, a gas introduction tube, a stirrer, and a thermometer, and hydrogen reduction treatment in advance Cu / SiO ₂ catalyst (10 g, 54% by mass of Cu in the catalyst, 10% by mass with respect to glycerol) and dihexylamine (201 g, 1 molar equivalent with respect to glycerol) were prepared. Covered. Next, nitrogen was circulated in the flask so as to bubble at a flow rate of 6 L / hour under atmospheric pressure, and the temperature was raised with sufficient stirring. The time when the reaction temperature reached 190 ° C. was defined as the reaction start time, and the reaction was performed at 190 ° C. for 3.5 hours. As a result of analyzing the reaction solution, conversion of glycerol was> 99%, and N, N-dihexylaminoacetone was 81%.

Example 2
The reaction was carried out for 3.7 hours in the same manner as in Example 1 except that hydrogen was supplied at a flow rate of 10 L / hour. As a result, conversion of glycerol was> 99%, and 79% of N, N-dihexylaminoacetone was produced.

Example 3
The reaction was carried out for 2.0 hours in the same manner as in Example 2 except that the reaction temperature was 200 ° C. As a result, the conversion rate of glycerin was> 99%, and 74% of N, N-dihexylaminoacetone was produced.

Example 4
The catalyst used for the reaction was Cu-Ni-Ru / zeolite (molar ratio; Cu: Ni: Ru = 4: 1: 0.25) prepared by referring to the method described in the specification of JP-A-3-83955. Was reacted in the same manner as in Example 1 for 5.0 hours. As a result, the conversion of glycerin was 87% and N, N-dihexylaminoacetone was 67%.

Example 5
A SUS 500 mL solenoid valve autoclave equipped with a reaction mixture sampling device, an exhaust gas outlet tube, a gas introduction tube, a stirrer, and a thermometer, glycerin (40 g), Cu manufactured by JGC Chemical Co., Ltd. previously subjected to hydrogen reduction treatment / SiO ₂ catalyst (1.2 g, 50% by mass of Cu in the catalyst, 3% by mass with respect to glycerol) and dihexylamine (97 g, 1.2 molar equivalents with respect to glycerol) were charged and sealed. The internal atmosphere was replaced several times with hydrogen and then filled with hydrogen at a pressure of 0.5 MPa. The temperature was then raised with sufficient stirring. When the internal temperature reached 200 ° C., 1.5 MPa of hydrogen was immediately charged, and the end of the charging was defined as the reaction start time. As a result of analyzing the reaction solution after reacting at 200 ° C. for 5 hours, the conversion of glycerin was 81%, and N, N-dihexylaminoacetone was 28%.

Example 6
In the same solenoid valve autoclave as in Example 5, glycerin (40 g), a Cu / SiO ₂ catalyst (0.76 g, Cu ratio in the catalyst of 50% by mass, glycerin, previously hydrogen-reduced) 1.9 mass%) and dihexylamine (97 g, 1.2 molar equivalents relative to glycerol) were charged and sealed. The internal atmosphere was replaced several times with nitrogen and sealed. The temperature was then raised with sufficient stirring. The time when the internal temperature reached 200 ° C. was defined as the reaction start time. As a result of analyzing the reaction solution after reacting at 200 ° C. for 5 hours, the conversion of glycerin was 51% and N, N-dihexylaminoacetone was 38%.

Example 7
The catalyst used for the reaction was anhydrous copper (II) acetate (1.2 g, 3% by mass with respect to glycerin) that had not been reduced, and the reaction temperature was 250 ° C. Reacted for hours. As a result, the conversion rate of glycerin was 45%, and N, N-dihexylaminoacetone was 13%.

Example 8
The reaction was carried out for 5.0 hours in the same manner as in Example 5 except that the catalyst used in the reaction was Cu-Fe-Al described in Example 1 of JP-A-4-22437. As a result, the conversion rate of glycerin was 38% and N, N-dihexylaminoacetone was produced 26%.

Comparative Example 1
A SUS 500 mL solenoid valve autoclave equipped with a reaction mixture sampling device, an exhaust gas outlet tube, a gas introduction tube, a stirrer, and a thermometer was added to glycerol (40 g), a Pt / C catalyst (1. 2 g, a Pt ratio in the catalyst of 5% by mass, 3% by mass with respect to glycerin) and dihexylamine (97 g, 1.2 molar equivalents with respect to glycerin) were charged and sealed. The internal atmosphere was replaced several times with hydrogen and then filled with hydrogen at a pressure of 0.5 MPa. The temperature was then raised with sufficient stirring. When the internal temperature reached 200 ° C., 1.5 MPa of hydrogen was immediately charged, and the end of the charging was defined as the reaction start time. As a result of analyzing the reaction solution after reacting at 200 ° C. for 5 hours, the conversion rate of glycerin was 2% and N, N-dihexylaminoacetone was 0.5%.

  The production method of α-aminoketone of the present invention is an economical and environmentally friendly and clean method, and is used as a production method of α-aminoketones important as various polymerization intermediates such as photopolymerization initiators or pharmaceuticals and agricultural chemicals. can do.

Claims (2)

Α-aminoketone in which glycerin or a trihydric or higher polyhydric alcohol (B), which is a compound having a glycerin structure at its terminal, is reacted with a secondary amine compound (C) in the presence of a catalyst (A) containing copper Compound production method. The method for producing an α-aminoketone compound according to claim 1, wherein a reducing gas and / or an inert gas is introduced into the reaction system.