JP5342887B2 - 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.

The α-aminoketone compounds are useful as raw materials and synthetic intermediates for various chemical products, photopolymerization initiators, pharmaceuticals, agricultural chemicals, and the like. 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 (see, for example, Patent Document 1 and Non-Patent Document 1). Thus, various proposals have been made to suppress side reactions and improve the yield.
For example, Patent Document 2 discloses a method of using a mixed solvent of water and alcohol and adjusting the molar ratio of 2-haloketone and amine in the solvent for reaction. 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 alcohol solvents. ing.

  On the other hand, a method for producing an α-aminoketone compound without using 2-haloketones as a starting material has been developed. In Patent Document 4, a sulfonium salt formed by reacting an organic sulfide and a free form (benzyl halide) having a leaving group bonded to a primary or secondary carbon atom was reacted with a ketone, and obtained. A method is disclosed in which an oxirane and an amine are reacted to form an α-amino alcohol and then selectively oxidized to produce an α-amino ketone.

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, examples using polyhydric alcohols as raw materials are known.
For example, Patent Document 5 discloses a method of aminating an alcohol in a gas phase in the presence of a hydrogenation catalyst impregnated with a solvent and hydrogen. Patent Document 6 discloses a method for producing an amino compound in which a polyhydric alcohol and ammonia or a primary or secondary amine are reacted in the presence of a catalyst containing copper, nickel, calcium, alkali metal, or alkaline earth metal. Is disclosed.

JP 60-120845 A JP-A-63-192744 International Publication No. 2003/91200 Pamphlet Special table 2008-505865 gazette Japanese Patent Laid-Open No. 9-20735 JP 2008-44930 A

J. et al. Am. Chem. Soc. 1928, 50, 2290

However, the method of Patent Document 1 has a problem that a high load is imposed on the environment because hydrogen halide or a neutralized salt thereof is by-produced in an equimolar amount during the reaction. Moreover, since the method of patent document 2 is a multistage reaction, it is industrially disadvantageous from a viewpoint of capital investment, a running cost, and waste disposal, and the load given to an environment is also large.
Patent Documents 5 and 6 only have a reaction example of a terminal diol, and do not show a reaction example in a trihydric or higher polyhydric alcohol having higher polarity and difficult to control the reaction.
As described above, there is no known example in which an α-aminoketone compound is synthesized in one step by an alcoholic amine production method using a trihydric or higher polyhydric alcohol as a raw material.
Therefore, an object of the present invention is to provide a method for producing an α-aminoketone compound in one step 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 secondary amine compound (C) in the presence of a catalyst (A) containing one or more metal components selected from cobalt, yttrium and palladium. A process for producing an α-aminoketone compound is provided.

  According to the present invention, an α-aminoketone compound can be produced from a trihydric or higher polyhydric alcohol in one step.

  The method for producing an α-aminoketone compound of the present invention comprises 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 cobalt, yttrium, and palladium. It is characterized by reacting with a secondary amine compound (C).

[Catalyst (A)]
The catalyst (A) used in the present invention contains at least one metal component selected from cobalt, yttrium, and palladium as a main component, and it is from the viewpoint of activity and economy that cobalt is a main component. preferable. Here, “containing as a main component” means that the catalyst metal component preferably contains the component in an amount of 50 mol% or more, more preferably 70 mol% or more, and still more preferably 90 mol% or more.
When the metal component contains cobalt, yttrium, and palladium, the molar ratio of each metal element is preferably Co: Y: Pd = 5 to 300: 1: 0.001-1, and Co: Y : Pd = 10 to 200: 1: 0.002 to 0.5 is more preferable, and Co: Y: Pd = 15 to 100: 1: 0.005 to 0.1 is more preferable.

The catalyst (A) may contain one kind or two or more kinds of metal components different from the main active metal component as an activity auxiliary component or composite component of the catalyst.
Examples of the activity auxiliary component and composite component of the catalyst include periodic tables 3 to 12 such as copper, nickel, ruthenium, aluminum, iron, platinum, rhodium, rhenium, iridium, molybdenum, chromium, manganese, zinc, vanadium, and zirconium. A group element can be used individually or in combination of 2 or more types.

The catalyst (A) can be appropriately prepared and used in a form such as a Raney type, a support type, a colloid type, a soluble type, a powder form, and a granular form.
The Raney-type catalyst means a porous sponge-like metal catalyst, and a commercially available product can also be used. The Raney-type catalyst can be prepared, for example, according to Teruo Kubo and Shinichiro Komatsu, “Raney Catalyst”, Kyoritsu Shuppan (1971)).
The supported catalyst is a catalyst in which a metal component is supported on a carrier in order to improve physical properties such as durability of the catalyst, and a commercially available product can also be used. The supported catalyst can be prepared by a known method such as precipitation, ion exchange, evaporation to dryness, spray drying, or kneading.
As a support | carrier, what is described in Studios in Surface and Catalysis, 1-25, vol51, 1989 etc. can be used, for example. More specifically, carbon (activated carbon), diatomaceous earth, clay, alumina, silica, titania, zirconia, ceria, silica-alumina composite oxides such as zeolite, and the like can be given. Among these, silica, alumina, zirconia, a composite oxide thereof, or carbon (activated carbon) is preferable.
The supported amount of the metal component in the supported catalyst is usually preferably about 0.10 to 70% by mass based on the total amount of the carrier and the supported metal component from the viewpoint of catalytic activity.
When a soluble catalyst is used, for example, an aqueous solution of a metal salt of an inorganic acid such as nitric acid or hydrochloric acid, or a mixed solution of various metal salts such as a complex may be dropped into the reaction system.

In the production method of the present invention, the catalyst (A) to be used is preferably separately reduced with hydrogen gas and another reducing agent from the viewpoint of improving the catalytic activity, and in a high boiling point solvent such as higher alcohol or liquid paraffin. In this case, it is possible to use a product which has been subjected to a reduction treatment while circulating hydrogen or continuously introducing another reducing agent and then filtered.
In addition, the reduction treatment is not performed in advance, and (i) the raw material polyhydric alcohol and the secondary amine compound are put together with the catalyst into the reactor and hydrogen gas is introduced, or (ii) the secondary reaction is performed. When the amine compound is in a gaseous state, it can be used after being subjected to a reduction treatment 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 total amount of metal components used in the catalyst is appropriately determined according to the type of polyhydric alcohol, but in the case of a batch reaction, the polyvalent amount of the raw material is selected from the viewpoints of reactivity, conversion rate and selectivity. 0.1 mass% or more is preferable as a metal with respect to alcohol, 0.5-50 mass% is more preferable, 1-20 mass% is further more preferable.

[Trihydric or higher polyhydric alcohol (B)]
As the trihydric or higher polyhydric alcohol (B) as a starting material, glycerin or a compound having a glycerin structure at the terminal is preferable. The α-aminoketone compound is obtained by reacting the glycerin structure with the secondary amine compound (C).
The total number of carbon atoms of the trihydric or higher polyhydric alcohol (B) is preferably 3 to 50, and more preferably 3 to 25.
More specifically, the trihydric or higher polyhydric alcohol (B) is preferably a polyhydric alcohol represented by the following formula (I) from the viewpoint of reactivity.

In 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.
Number of carbon atoms in the hydrocarbon group is R ¹ is preferably 1 to 47, 1 to 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 (B) represented by the formula (I) include glycerin, aliphatic polyhydric alcohols and related compounds, various sugar alcohols and related compounds.
Examples of aliphatic polyhydric alcohols and related compounds include 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-methoxy- , And 2,3-pentane triol.

Examples of various sugar alcohols and related compounds thereof include erythritol, threitol, ribitol, arabinitol, xylitol, allitol, sorbitol, mannitol, iditol, galactitol, taritol, boremitol, perseitol and the like.
Among the polyhydric alcohols (B), glycerin, 1,2,3-butanetriol, and erythritol are preferable, and glycerin is particularly preferable.

[Secondary amine compound (C)]
As the secondary amine compound (C) as a starting material, a compound represented by the following formula (II) is preferable.

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.
Number of carbon atoms in the hydrocarbon group is R ² is 1 to 40 preferably 1 to 20 is more preferable.

Secondary amine compounds represented by the formula (II) include dialkylamines and related compounds, diarylamines and related compounds, arylalkylamines and related compounds, cyclic amines and related compounds, and secondary compounds such as proline. Examples thereof include amino acids having an amino group and related compounds thereof.
Dialkylamine and its related compounds include dimethylamine, diethylamine, dipropylamine, dibutylamine, dipentylamine, dihexylamine, diheptylamine, dioctylamine, dinonylamine, didecylamine, diundecylamine, didodecylamine, ditridecylamine, Ditetradecylamine, dipentadecylamine, dihexadecylamine, diheptadecylamine, dioctadecylamine, methylethylamine, methylpropylamine, ethylpropylamine, methylbutylamine, methylpentylamine, methylhexylamine, methylheptylamine, Examples thereof include dialkylamines such as methyloctylamine, methyldodecylamine, methylstearylamine, and similar compounds.

Examples of the arylalkylamine and its related compounds include diphenylamine, dibenzylamine, methylphenylamine, ethylphenylamine, methylbenzylamine, and ethylbenzylamine.
Examples of the cyclic amine and its related compounds include morpholine, pyrrolidine, piperazine, and isoindoline.
Among the secondary amine compounds, dialkylamines and related compounds thereof are preferable, and dialkylamines having an alkyl group having 1 to 22 carbon atoms, preferably 1 to 12 carbon atoms such as dimethylamine, diethylamine, dihexylamine, and didecylamine are preferable. More preferred.

In the production method of the present invention, the charged amount of the secondary amine compound (C) to the trihydric or higher polyhydric alcohol (B) is 0.7 in terms of mole from the viewpoint of the reactivity and the yield of the target product. The 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, 20 equivalents or less are preferable in terms of moles, and 10 equivalents or less are more preferable.
The method for adding the secondary amine compound (C) is not particularly limited, and examples thereof include a continuous addition method, a method in which the whole amount is charged from the beginning, a method in which a predetermined amount is divided and introduced into the reaction system as appropriate. .

[Reaction conditions]
The reaction in the method of the present invention is preferably performed in an atmosphere of a reducing gas and / or an inert gas from the viewpoint of reaction efficiency and selectivity.
In this case, hydrogen can usually be used as the reducing gas introduced into the reaction system, 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 of two or more.

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 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 ° C is preferred, 150-250 ° C is more preferred, and 170-230 ° C is even more preferred.
In this case, sufficient catalytic activity can be exhibited at 100 ° C. or higher, and at 350 ° C. or lower, trihydric or higher polyhydric alcohol (B), secondary amine compound (C) or product. It is preferable from the viewpoint of suppression of decomposition and excessive reaction.

  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. For example, the trihydric or higher polyhydric alcohol (B) is glycerin, 1,2,3-butanetriol or erythritol, and the secondary amine compound (C) is dimethylamine, diethylamine or dihexyl. In the case of amine or didecylamine, from the viewpoint of industrialization, 0.001 to 30 MPa is preferable, 0.01 to 15 MPa is more preferable, and 0.1 to 5 MPa is further preferable.

In the following examples and comparative examples, the conversion of polyhydric alcohol, the production confirmation of the α-aminoketone compound and the determination of the yield are determined by gas chromatography (GC) and gas chromatography / mass spectrometry (GC / MS). Used.
For the sample used for GC analysis, 1 drop of the reaction product is taken in a 10 ml sample bottle, and a trimethylsilyl (TMS) agent (manufactured by GL Science Co., Ltd.) is placed therein and heated at 40 ° C. for about 5 minutes. Further, 1.5 ml of hexane was added thereto for dilution, and then the mixture was filtered through a membrane filter 0.2 μm.

Example 1
(1) Preparation of catalyst precursor A mixed aqueous solution of cobalt nitrate, yttrium nitrate, and palladium nitrate in which the molar ratio of the metal elements is Co: Y: Pd = 20: 1: 0.016 is gradually added dropwise to the aqueous sodium carbonate solution. The mixture was stirred and mixed at room temperature. The resulting precipitate was sufficiently washed with water, dried at 100 ° C., and calcined at 500 ° C. for 4 hours to obtain a catalyst precursor.
(2) Activation of catalyst The catalyst precursor obtained in (1) above is placed in an electric furnace capable of a reducing atmosphere, and up to 500 ° C while flowing 4% [v / v] of hydrogen diluted with nitrogen. The temperature was raised and reduction treatment was performed until no hydrogen absorption was observed. Next, the inside of the system was purged with nitrogen, cooled to room temperature, and then air diluted with nitrogen (oxygen concentration 1% [v / v]) was circulated to stabilize the surface of the reduction catalyst by oxidation. Oxidation stabilization treatment was performed until oxygen absorption was not observed, and a catalyst was obtained.
(3) Production of aminoketone 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 40 g of glycerin and Co-- obtained in (2) above. Y-Pd catalyst 1.2g (3 mass% with respect to glycerol) and dihexylamine 97g (1.2 molar equivalent with respect to glycerol) were prepared, and it sealed. The internal atmosphere was replaced several times with hydrogen and then filled with hydrogen at a pressure of 0.5 MPa.
Next, the temperature was raised with sufficient stirring, and 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 3 hours, the conversion rate of glycerin was 99% or more, and 23% of N, N-dihexylaminoacetone was produced.

Comparative Example 1
In Example 1, the reaction was performed for 3.0 hours in the same manner as in Example 1 except that the catalyst was a Pt / C catalyst manufactured by N.E. As a result, the conversion of glycerol was 1.2%, and 0.3% of N, N-dihexylaminoacetone was produced.

  The method of the present invention is an economical and environmentally friendly method capable of producing an α-aminoketone compound from a trihydric or higher polyhydric alcohol in one step. Various chemical products, photopolymerization initiators, pharmaceuticals, agricultural chemicals It can utilize as a manufacturing method of alpha-amino ketones important as raw materials and synthetic intermediates.

Claims (5)

Cobalt, yttrium, and in the presence of a catalyst (A) containing palladium, glycerine (B) and the secondary amine compound (C) in the method of manufacturing the α- amino acetone reacting. Secondary amine compound (C) is a dialkyl amine having an alkyl group of 1 to 22 carbon atoms, a manufacturing method of the α- amino acetone claim 1. Catalyst (A) are those containing cobalt as a main component, method for producing α- amino acetone according to claim 1 or 2. The manufacturing method of alpha-aminoacetone in any one of Claims 1-3 whose content of cobalt is 70 mol% or more in a catalyst metal component. It is reacted in an atmosphere of reducing gas and / or inert gas, the manufacturing method of the α- amino acetone according to claim 1.