JP2015151368A - Method of producing bicyclic amine compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of efficiently producing a bicyclic amine compound while improving a color tone of it.SOLUTION: A method of producing a bicyclic amine compound includes a reaction step in which the formula (1) is made to react in a gas phase in the presence of a solid catalyst such as an inorganic oxide and a metal phosphoric acid, to produce a bicyclic amine compound of the formula (2), and a distillation step.

Description

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

  Bicyclic amine compounds are known as compounds useful for, for example, pharmaceutical and agrochemical intermediates, organic synthesis catalysts, chemical adsorbents, antibacterial agents and the like.

  As a method for producing such a compound, the applicant has the following formula:

［上記式中、Ｒ_１〜Ｒ_８は各々独立して、水素原子、炭素数１〜４のアルキル基、水酸基、ヒドロキシメチル基、又は炭素数１〜４のアルコキシ基を表す。また、Ｘは炭素原子又は窒素原子を表し、Ｙは水素原子、アルキル基、水酸基、又は炭素数１〜４のヒドロキシアルキル基を表す。］
で示される化合物を、固体触媒存在下、気相中で分子内脱水させ、下記式

[In the above formula, R _{1 to} R ₈ each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group, or an alkoxy group having 1 to 4 carbon atoms. X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. ]
In the presence of a solid catalyst, the compound represented by

［上記式中、Ｙ、Ｒ_１〜Ｒ_８は前記と同じ定義である。］
で示される二環式アミン化合物を製造する方法であって、上記固体触媒として、下記式

[Wherein, Y and R _{1 to} R ₈ have the same definitions as above. ]
Wherein the solid catalyst is represented by the following formula:

［上記式中、ＡはＳｉ、Ａｌ、Ｍｇ、Ｔｉ及びＺｒからなる群より選ばれる１種又は２種以上の元素を表し、Ｍはアルカリ金属元素又はアルカリ土類金属元素を表し、Ｐはリンを表し、Ｏは酸素を表す。添字ａ〜ｄは各元素のモル数を表し、ｂ／ａ＝０．００１〜０．３（モル比）、ｃ／ａ＝０．００１〜０．３（モル比）であって、ｄは各原子の結合状態によって任意に取り得る値を表す。ただし、Ａが２種以上の元素を表す場合には、添字ａはそのモル数が最も大きい元素のモル数を表す。］
で示される無機酸化物を用いることを特徴とする製造方法について、既に特許出願している（特許文献１参照）。

[In the above formula, A represents one or more elements selected from the group consisting of Si, Al, Mg, Ti and Zr, M represents an alkali metal element or an alkaline earth metal element, and P represents phosphorus. O represents oxygen. Subscripts a to d represent the number of moles of each element, b / a = 0.001 to 0.3 (molar ratio), c / a = 0.001 to 0.3 (molar ratio), and d is It represents a value that can be arbitrarily taken depending on the bonding state of each atom. However, when A represents two or more elements, the subscript a represents the number of moles of the element having the largest number of moles. ]
A patent application has already been filed for a production method characterized by using an inorganic oxide represented by (see Patent Document 1).

  Gaseous bicyclic amines produced by a gas phase reaction are usually collected by cooling once and then purified by, for example, a recrystallization method or a distillation method. However, the recrystallization method is not efficient because a high-purity product can be obtained, but the remaining amount in the mother liquor is large, requiring multiple operations and recycling of the recrystallization solvent. . In addition, the distillation method has a problem that the hue of the product is deteriorated due to thermal decomposition of the bicyclic amine itself or impurities or side reaction during distillation.

  As a general means for improving the hue of a product, for example, a method of improving distillation conditions such as temperature and pressure, or a method using an additive such as an antioxidant is known (for example, see Patent Documents 2 and 3). . However, there are restrictions on equipment and the like for improving the distillation conditions, and the additive itself may adversely affect the product, and there is still room for improvement.

JP 2012-149048 A JP 2003-113171 A JP 2007-45795 A

  This invention is made | formed in view of said background art, The objective is to provide the manufacturing method which can improve the hue of a bicyclic amine compound and can be obtained efficiently.

  As a result of intensive studies to solve the above problems, the present inventors have completed the present invention. That is, this invention is a manufacturing method of the bicyclic amine compound as shown below.

  [1] The following formula (1)

［上記式（１）中、Ｘはアミノ基又は水酸基を表し、Ｙは水素原子、炭素数１〜４のアルキル基、又は炭素数１〜４のヒドロキシアルキル基を表し、Ｒ_１〜Ｒ_８は各々独立して、水素原子、炭素数１〜４のアルキル基、ヒドロキシアルキル基、又は水酸基を表す。］
で示される化合物を、固体触媒存在下、気相中で反応させ、下記式（２）

[In the above formula (1), X represents an amino group or a hydroxyl group, Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a hydroxyalkyl group having 1 to 4 carbon _atoms, R 1 to R ₈ is Each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group, or a hydroxyl group. ]
Is reacted in the gas phase in the presence of a solid catalyst, and the following formula (2)

［上記式（２）中、Ｙ、Ｒ_１〜Ｒ_８は前記と同じ定義である。］
で示される二環式アミン化合物を製造する反応工程、反応工程で得られた反応液を気液分離装置に供給し、１４０℃以上３００℃以下の温度で気液分離する気液分離工程、及び気液分離工程で得られた気体を凝集後、蒸留精製する蒸留工程を含む二環式アミン化合物の製造方法。

[In the above formula (2), Y and R _{1 to} R ₈ have the same definitions as above. ]
A reaction step for producing a bicyclic amine compound represented by formula (1), a gas-liquid separation step for supplying the reaction liquid obtained in the reaction step to a gas-liquid separation device, and gas-liquid separation at a temperature of 140 ° C. or higher and 300 ° C. or lower, and A method for producing a bicyclic amine compound, comprising a distillation step in which the gas obtained in the gas-liquid separation step is condensed and then purified by distillation.

  [2] The method for producing a bicyclic amine compound according to the above [1], wherein in the formula (1), Y is a hydrogen atom, an aminomethyl group, or a hydroxymethyl group.

  [3] The method for producing a bicyclic amine compound according to the above [1], wherein in the formula (1), Y is a hydrogen atom or a hydroxymethyl group.

  [4] The method for producing a bicyclic amine compound according to any one of the above [1] to [3], wherein in the formula (1), X is a hydroxyl group.

[5] The method for producing a bicyclic amine compound according to any one of the above [1] to [4], wherein in the formula (1), R _{1 to} R ₈ are hydrogen atoms.

  [6] The method for producing a bicyclic amine compound according to any one of the above [1] to [5], wherein the gas-liquid separation is performed at a temperature of 180 ° C. or higher and 300 ° C. or lower.

  [7] The method for producing a bicyclic amine compound according to any one of [1] to [6], wherein the gas-liquid separation is performed at a temperature of 180 ° C. or higher and 260 ° C. or lower.

  According to the production method of the present invention, a bicyclic amine compound having an improved hue as compared with the conventional method can be efficiently obtained.

The method for producing the bicyclic amine of the present invention comprises:
(1) a reaction step of producing a bicyclic amine compound represented by the above formula (2) by reacting the compound represented by the above formula (1) in a gas phase in the presence of a solid catalyst,
(2) The reaction liquid obtained in the reaction step is supplied to the gas-liquid separation device, and the gas-liquid separation step for gas-liquid separation at a temperature of 140 ° C. or higher and 300 ° C. or lower; and (3) the gas-liquid separation step. The method is characterized by including a distillation step of distilling and purifying the gas after aggregation.

  First, the reaction process of this invention is demonstrated.

In the above formulas (1) and (2), X represents an amino group or a hydroxyl group, Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a hydroxyalkyl group having 1 to 4 carbon atoms, R ₁ to R ₈ each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group, or a hydroxyl group.

  Examples of the compound represented by the formula (1) include compounds 1 to 6 shown below, but the present invention is not limited thereto.

また、上記式（２）で示される二環式アミン化合物の具体例としては、例えば、以下に示される化合物７〜１０を挙げることができるが、本発明はこれらに限定されるものではない。

Specific examples of the bicyclic amine compound represented by the above formula (2) include compounds 7 to 10 shown below, but the present invention is not limited thereto.

反応工程において使用される固体触媒として、例えば、無機酸化物が用いられる。無機酸化物としては、特に限定するものでは無いが、例えば、酸化ケイ素、酸化アルミニウム、アルミノシリケート、ゼオライト、酸化マグネシウム、酸化チタン、酸化ジルコニウム等が用いられる。

As the solid catalyst used in the reaction step, for example, an inorganic oxide is used. The inorganic oxide is not particularly limited, and for example, silicon oxide, aluminum oxide, aluminosilicate, zeolite, magnesium oxide, titanium oxide, zirconium oxide and the like are used.

  As another catalyst, for example, a metal phosphate can also be used. Although it does not specifically limit as a metal phosphate, For example, metal salts, such as phosphoric acid, phosphorous acid, and hypophosphorous acid, are mentioned. Examples of metals that form salts with phosphoric acid include sodium, potassium, lithium, calcium, barium, magnesium, aluminum, lanthanum, titanium, iron, cobalt, nickel, copper, zinc, zirconium, palladium, silver, tin, and lead. Etc.

  The above-mentioned oxides or metal phosphates can be used alone, but can be used in combination of two or more, and in addition to these, an acid component, a base component, or these It is also possible to use both components supported.

  Although it does not specifically limit as an acid component, For example, a sulfuric acid, phosphoric acid, boric acid, heteropoly acid etc. are mentioned.

  Although it does not specifically limit as a base component, For example, Na, K, Rb, Cs, Ca, Sr, Ba, Ce, La etc. are mentioned.

  The raw material for such a base component is not particularly limited, and examples thereof include oxides, hydroxides, halides, carbonates, nitrates, and sulfates thereof.

  In the present invention, the method for preparing the solid catalyst is not particularly limited, and a generally performed preparation method is employed. For example, a method of dissolving or suspending the above-described solid catalyst raw material in water, stirring, heating, concentrating, drying, molding, and further calcination to obtain a solid catalyst can be mentioned.

  In the present invention, the firing of the solid catalyst is not particularly limited, but may be performed in an air or nitrogen atmosphere.

  In the present invention, the reaction step is performed in a gas phase and a fixed bed flow type.

  In the reaction step, nitrogen, argon, hydrogen, ammonia, water vapor or hydrocarbon gas can be used as the dilution gas.

  These dilution gases can be used in any amount and are not particularly limited, but the reaction substrate / dilution gas molar ratio is preferably in the range of 0.01-1.

  In the reaction step, the reaction temperature is usually in the range of 200 to 500 ° C.

  Next, the gas-liquid separation process of the present invention will be described.

  In the present invention, the gaseous bicyclic amine compound generated in the reaction step liquefies a high-boiling component (hereinafter referred to as “tar content”) at a predetermined temperature, and then the gas-liquid separation device. Provided. By removing the tar content in advance, hue deterioration due to side reactions during distillation is reduced, so that the hue of the product is improved without using an additive such as an antioxidant.

  In the gas-liquid separation step, it is important to supply the reaction liquid obtained in the reaction step to a gas-liquid separation device and perform gas-liquid separation at a temperature of 140 ° C. or higher and 300 ° C. or lower. Specifically, gas-liquid separation may be performed by setting the temperature inside the gas-liquid separator to 140 ° C. or higher and 300 ° C. or lower. In a high temperature range exceeding 300 ° C., the tar content is not sufficiently liquefied and used for the next distillation step, which causes deterioration of the hue. On the contrary, in the temperature range lower than 140 ° C., the target bicyclic amine compound is liquefied and trapped in the gas-liquid separator, so that the process yield is lowered.

  In the gas-liquid separation step, the process yield is further improved by setting the temperature of gas-liquid separation to 180 ° C. or higher and 300 ° C. or lower, and by adjusting the temperature to 180 ° C. or higher and 260 ° C. or lower, the target bicyclic amine compound Hue is further improved.

  The method of the gas-liquid separator is not particularly limited. For example, a knockout (KO) drum method, a cyclone method, a demister mesh method, and the like are adopted. The demister mesh method is preferred from the viewpoint of tar collection efficiency and equipment size.

  The size of the gas-liquid separator and the flow rate of the passing gas are not particularly limited as long as the droplet repair efficiency is sufficient and the resulting pressure loss does not interfere with continuous operation.

  In the present invention, a cleaning line may be provided in the gas-liquid separation device in order to avoid operation stoppage due to blockage of the device. Although it does not specifically limit as a washing | cleaning solvent, Water, methanol, ethanol, isopropanol, ethylene glycol, propylene glycol, polyethylene glycol, porpropylene glycol, acetone, THF, hexane, toluene etc. are mentioned.

  Next, the distillation process of the present invention will be described.

  The gaseous bicyclic amine compound collected from the gas-liquid separator is agglomerated by a condenser, a condenser tube, etc., and then separated from low boiling point by-products by atmospheric distillation. Subsequently, the residue in the kettle is distilled under reduced pressure to be separated from high boiling point by-products.

  The distillation apparatus used for distillation is not particularly limited, and a known distillation apparatus such as a batch distillation apparatus, a continuous distillation apparatus, or a column type distillation apparatus can be used. When industrially distilling in large quantities, it is preferable to use a continuous rectification apparatus comprising a heater, a rectification column and a condenser.

  By the above method, it is possible to efficiently obtain a bicyclic amine compound having a better hue than the conventional method in which gas-liquid separation is not performed.

  The invention is illustrated in more detail by the following examples.

Example 1 Production of a bicyclic amine (boiling point 174 ° C.) in which Y and R _{1 to} R ₈ are hydrogen atoms in the above formula (2).
[Reaction process]
A 10 wt% aqueous solution was prepared using aminoethylpiperazine (commercially available product) in which X is an amino group, Y is a hydrogen atom, and R _{1 to} R ₈ are hydrogen atoms as a raw material. A SUS reaction tube is filled with ceramic balls as a catalyst holding agent and 200 cc of a molded product of H-type zeolite (ZSM-5) as a solid catalyst, and then an aqueous raw material solution is supplied at 3.0 cc / min, and the catalyst layer temperature is set. The reaction was performed at 380 ° C.

[Gas-liquid separation process]
At the outlet of the reaction tube, a gas-liquid separator made of SUS filled with demister mesh (H-STYLE: manufactured by Nippon Mesh Industrial Co., Ltd.) was installed, and the temperature of the device was adjusted within the temperature range shown in Table 1. The internal temperature of the gas-liquid separator was set to 140 ° C. or higher and 300 ° C. or lower.

[Distillation process]
The gaseous bicyclic amine compound collected from the gas-liquid separator was aggregated through a condenser, and water and low-boiling by-products were removed by atmospheric distillation. Subsequently, distillation was performed at a pressure of 5 mmHg, a kettle bottom temperature of 210 to 235 ° C., and a reflux ratio of 5, and a target product was collected. Table 1 shows the yield of the bicyclic amine compound and the Gardner color number for each internal temperature of the gas-liquid separator.

目的物の定量は、ガスクロマトグラフィーを用いた内部標準法にて行った。色度の評価は、得られた二環式アミン化合物を５０重量％のメタノール溶液とした上で、ｃｏｌｏｒ ｍｅｔｅｒ Ｚｅ６０００（日本電色工業社製）を用いて行った。

The target product was quantified by an internal standard method using gas chromatography. The evaluation of chromaticity was performed using a color meter Ze6000 (manufactured by Nippon Denshoku Industries Co., Ltd.) after making the obtained bicyclic amine compound a 50% by weight methanol solution.

Comparative Example 1
In Example 1, the yield and the number of Gardner colors when the internal temperature of the gas-liquid separator is 120 ° C. and 330 ° C. and when the gas-liquid separation operation is not performed are also shown in Table 1.

Example 2 Production of a bicyclic amine (boiling point 174 ° C.) in which Y and R _{1 to} R ₈ are hydrogen atoms in the above formula (2).
A commercially available hydroxyethylpiperazine in which X is a hydroxyl group, Y is a hydrogen atom, and R _{1 to} R ₈ are hydrogen atoms in the above formula (1) is used as a raw material, and 200 cc of an aluminum phosphate molded body is used as a catalyst. The target product was collected in the same manner as in Example 1, quantified, and the chromaticity was evaluated. Table 2 shows the yield of the bicyclic amine compound and the Gardner color number for each internal temperature of the gas-liquid separator.

比較例２．
実施例２において、気液分離装置の内部温度を１２０℃、３３０℃にした場合、及び気液分離操作を行わない場合の収率、及びガードナー色数を、表２に併せて示す。

Comparative Example 2
In Example 2, Table 2 shows the yield and the number of Gardner colors when the internal temperature of the gas-liquid separator is 120 ° C. and 330 ° C. and when the gas-liquid separation operation is not performed.

Preparation Example 1 Synthesis of N- (2,3-dihydroxypropyl) piperazine.
A 200 ml three-necked flask was charged with 86.1 g (1.0 mol) of piperazine and 100 ml of methanol as a solvent, and 22.2 g (0.3 mol) of glycidol was added dropwise over 4 hours under a nitrogen atmosphere. The temperature of the reaction solution was kept at 60 ° C. by holding the three-necked flask in an oil bath. After completion of the addition of glycidol, methanol as a solvent in the reaction solution and unreacted piperazine were distilled off by simple distillation. The product was vacuum-dried to obtain 45.2 g of a white viscous solid. It was confirmed by gas chromatography mass spectrometry and nuclear magnetic resonance analysis that this substance was N- (2,3-dihydroxypropyl) piperazine.

Preparation Example 2 Preparation of gas phase reaction catalyst.
200 g of amorphous dry silica (ox-50, manufactured by Nippon Aerosil Co., Ltd.) as a catalyst carrier was mixed with 500 ml of water to form a slurry solution, and 64.9 g of cesium nitrate and 26.4 g of diammonium hydrogen phosphate were mixed and dispersed. Thereafter, it was evaporated to dryness using an evaporator to obtain a white solid. This solid was compression molded, calcined at 600 ° C. for 4 hours in a muffle furnace under a nitrogen atmosphere, and pulverized to 2.5 to 3.5 mesh to obtain a gas phase reaction catalyst.

Example 3 Production of a bicyclic amine (boiling point 180 ° C.) in which Y is a hydroxyalkyl group having 1 carbon atom and R _{1 to} R ₈ are hydrogen atoms in the above formula (2).
As a raw material, N- (2,3-dihydroxy) obtained in Preparation Example 1, wherein X is a hydroxyl group, Y is a hydroxyalkyl group having 1 carbon atom, and R _{1 to} R ₈ are hydrogen atoms. Propyl) piperazine was used, and the target product was collected and quantified in the same manner as in Example 1 except that 200 cc of the gas phase reaction catalyst obtained in Preparation Example 2 was used, and chromaticity was evaluated. Table 3 shows the yield of the bicyclic amine compound and the Gardner for each internal temperature of the gas-liquid separator.

比較例３．
実施例３において、気液分離装置の温度を１２０℃、３３０℃にした場合、及び気液分離操作を行わない場合の収率、及びガードナー色数を、表３に併せて示す。

Comparative Example 3
In Example 3, Table 3 shows the yield and the number of Gardner colors when the temperature of the gas-liquid separator is 120 ° C. and 330 ° C. and when the gas-liquid separation operation is not performed.

  As is clear from the above results, gas-liquid separation is performed by performing a gas-liquid separation operation at a temperature of 140 ° C. or higher and 300 ° C. or lower prior to distillation purification on the gaseous product obtained after the gas phase reaction. Compared with the case where the operation was not performed, a bicyclic amine compound having a good hue could be obtained in a high yield.

  The bicyclic amine compound production method of the present invention is used, for example, for the production of bicyclic amine compounds known as useful compounds for medicines and agricultural chemicals intermediates, catalysts for organic synthesis, chemical adsorbents, antibacterial agents and the like. There is a possibility that.

Claims (7)

Following formula (1)

[In the above formula (1), X represents an amino group or a hydroxyl group, Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a hydroxyalkyl group having 1 to 4 carbon _atoms, R 1 to R ₈ is Each independently represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyalkyl group, or a hydroxyl group. ]
Is reacted in the gas phase in the presence of a solid catalyst, and the following formula (2)

[In the above formula (2), Y and R _{1 to} R ₈ have the same definitions as above. ]
A reaction step for producing a bicyclic amine compound represented by formula (1), a gas-liquid separation step for supplying the reaction liquid obtained in the reaction step to a gas-liquid separation device and gas-liquid separation at a temperature of 140 ° C. or higher and 300 ° C. or lower; A method for producing a bicyclic amine compound, comprising a distillation step in which the gas obtained in the gas-liquid separation step is condensed and then purified by distillation. In the said Formula (1), Y is a hydrogen atom, an aminomethyl group, or a hydroxymethyl group, The manufacturing method of the bicyclic amine compound of Claim 1. In the said Formula (1), Y is a hydrogen atom or a hydroxymethyl group, The manufacturing method of the bicyclic amine compound of Claim 1. The method for producing a bicyclic amine compound according to any one of claims 1 to 3, wherein in the formula (1), X is a hydroxyl group. In formula (1), R < ₁ > -R < ₈ > is a hydrogen atom, The manufacturing method of the bicyclic amine compound in any one of Claims 1 thru | or 4. The method for producing a bicyclic amine compound according to any one of claims 1 to 5, wherein the gas-liquid separation is performed at a temperature of 180 ° C or higher and 300 ° C or lower. The method for producing a bicyclic amine compound according to any one of claims 1 to 6, wherein the gas-liquid separation is performed at a temperature of 180 ° C or higher and 260 ° C or lower.