JP2014105194A - Method for producing bicyclic amine compound - Google Patents
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Abstract
Description
本発明は二環式アミン化合物の製造法に関する。 The present invention relates to a method for producing a bicyclic amine compound.
二環式アミン化合物は、例えば、医農薬中間体、有機合成用触媒、化学吸着剤、抗菌剤等に有用な化合物として知られている（例えば、特許文献１、２参照）。 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 (see, for example, Patent Documents 1 and 2).
二環式アミン化合物の製造法として、特許文献１では、エステル基を置換基に有する二環式アミン化合物を合成した後、エステル基を還元することにより誘導している。 As a method for producing a bicyclic amine compound, in Patent Document 1, a bicyclic amine compound having an ester group as a substituent is synthesized and then the ester group is reduced.
しかしながら、この製造法は、還元剤として発火の危険性が高い水素化リチウムアルミニウムを使用するため、工業的なスケールアップ製造上好ましいと言えない。また高価な反応基質を使用することから実用的とは言えない状況にある。 However, since this production method uses lithium aluminum hydride, which has a high risk of ignition, as a reducing agent, it is not preferable for industrial scale-up production. In addition, since an expensive reaction substrate is used, it is not practical.
このため、本件出願人は、一段階で目的物が得られる上、過度な高圧反応が不要な簡便且つ安全な製造法として、下記式 For this reason, the applicant of the present invention can obtain the target product in one step and, as a simple and safe production method that does not require excessive high-pressure reaction,
で示されるジヒドロキシアルキルピペラジン類を、酸触媒の存在下で分子内脱水縮合反応させて、二環式アミン化合物を製造する方法について既に特許出願している（特許文献２参照）。
A patent application has already been filed for a method for producing a bicyclic amine compound by subjecting a dihydroxyalkylpiperazine represented by formula (I) to an intramolecular dehydration condensation reaction in the presence of an acid catalyst (see Patent Document 2).
特許文献２に記載の方法は、多段階の反応が不要であり、発火の危険性が高い還元剤を用いることなく、簡便且つ安全に二環式アミン化合物を製造することができるという優れた方法ではあるが、転化率が十分でないために未反応原料の回収工程が必要になることや、この製造法における酸触媒を気相反応に適用すると、十分な収率が得られない上に反応副生物がタール状となって析出し、反応管を閉塞させる場合があるため、工業的に連続生産する上で未だ改善すべき問題があった。 The method described in Patent Document 2 is an excellent method in which a multi-step reaction is unnecessary, and a bicyclic amine compound can be easily and safely produced without using a reducing agent having a high risk of ignition. However, since the conversion rate is not sufficient, a step for recovering unreacted raw materials is necessary, and when the acid catalyst in this production method is applied to a gas phase reaction, a sufficient yield cannot be obtained and a reaction by-product is not obtained. Since organisms may be deposited in the form of tar and clog the reaction tube, there are still problems to be solved in industrial continuous production.
このため本件出願人は、二環式アミン化合物を簡便に且つ高収率で得ることができ、また連続生産の支障となる副生タール分が抑制できる製造法として、下記式 For this reason, the applicant of the present invention can obtain a bicyclic amine compound easily and in a high yield, and a production method capable of suppressing a by-product tar component that hinders continuous production is represented by the following formula.
で示される化合物を、固体触媒として、式ＡａＭｂＰｃＯｄ［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の存在下、気相中で分子内脱水させて、二環式アミン化合物を製造する方法について、既に特許出願している（特許文献３参照）。
As a solid catalyst, a compound represented by the formula A a M b P c O d [wherein 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 alkaline earth metal element, P represents phosphorus, and 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 method for producing a bicyclic amine compound by intramolecular dehydration in the gas phase in the presence of an inorganic oxide represented by the formula (see Patent Document 3).
特許文献３には、気相反応による製造法が示されており、特定の固体触媒を使用することにより、副生タール分が低減できることが記載されている。しかしながら、触媒のコーキングについて検討がなされておらず、また長期の運転評価も約１週間程度の実施に留まっているため、工業的に連続生産する上では未だ改善すべき問題があった。 Patent Document 3 discloses a production method by gas phase reaction, and describes that by-product tar content can be reduced by using a specific solid catalyst. However, since the caulking of the catalyst has not been studied and the long-term operation evaluation has only been conducted for about one week, there is still a problem to be improved in industrial continuous production.
本発明は、上記の背景技術に鑑みてなされたものであり、その目的は、工業的な二環式アミン化合物の製造法を提供することである。 The present invention has been made in view of the above-described background art, and an object thereof is to provide an industrial method for producing a bicyclic amine compound.
本発明者らは、上記課題を解決すべく鋭意検討を重ねた結果、本発明を完成するに至った。すなわち、本発明は以下に示すとおりの二環式アミン化合物の製造法である。 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］下記式（１）で示される化合物を含む原料体を気相中で固体触媒に接触させ１次反応体とする工程（Ａ）と、当該１次反応体を気相中で当該固体触媒に接触させ２次反応体とする工程（Ｂ）とを含むことを特徴とする下記式（２）で示される二環式アミン化合物の製造法。 [1] A step (A) in which a raw material containing a compound represented by the following formula (1) is brought into contact with a solid catalyst in a gas phase to form a primary reactant, and the primary reactant is converted into the solid in the gas phase. A process for producing a bicyclic amine compound represented by the following formula (2), which comprises a step (B) of contacting with a catalyst to form a secondary reactant.
［２］式（１）及び（２）において、Ｙが水素原子又はヒドロキシメチル基であることを特徴とする上記［１］に記載の二環式アミン化合物の製造法。
[2] The method for producing a bicyclic amine compound as described in [1] above, wherein in formulas (1) and (2), Y is a hydrogen atom or a hydroxymethyl group.
［３］式（１）及び（２）において、Ｘが窒素原子であることを特徴とする上記［１］又は［２］に記載の二環式アミン化合物の製造法。 [3] The method for producing a bicyclic amine compound according to the above [1] or [2], wherein in the formulas (1) and (2), X is a nitrogen atom.
［４］式（１）及び（２）において、Ｘが窒素原子であり、かつＹがヒドロキシメチル基であることを特徴とする上記［１］又は［２］に記載の二環式アミン化合物の製造法。 [4] The bicyclic amine compound according to the above [1] or [2], wherein in the formulas (1) and (2), X is a nitrogen atom and Y is a hydroxymethyl group Manufacturing method.
［５］式（１）及び式（２）において、Ｒ１〜Ｒ８が各々独立して、水素原子、メチル基、エチル基、イソプロピル基又はヒドロキシメチル基を表す（ただし、Ｒ１〜Ｒ８が全て同じ置換基になることはない。）ことを特徴とする上記［１］乃至［４］のいずれかに記載の二環式アミン化合物の製造法。 [5] In Formula (1) and Formula (2), R1 to R8 each independently represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, or a hydroxymethyl group (provided that R1 to R8 are all the same substituents) The method for producing a bicyclic amine compound according to any one of [1] to [4] above, wherein the bicyclic amine compound is not a group.
［６］式（１）及び式（２）において、Ｒ１〜Ｒ８が水素原子を表すことを特徴とする上記［１］乃至［４］のいずれかに記載の二環式アミン化合物の製造法。 [6] Production of a bicyclic amine compound according to any one of the above [1] to [4], wherein in formulas (1) and (2), R 1 to R 8 represent a hydrogen atom. Law.
［７］固体触媒として、下記式（３）で示される無機酸化物を用いることを特徴とする上記［１］乃至［６］のいずれかに記載の二環式アミン化合物の製造法。 [7] The process for producing a bicyclic amine compound according to any one of the above [1] to [6], wherein an inorganic oxide represented by the following formula (3) is used as the solid catalyst.
ＡｌａＭｂＰｃＯｄ （３）
［上記式（３）中、Ａｌはアルミニウムを表し、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。］
［８］上記式（３）において、ＭがＮａ，Ｋ、Ｒｂ、Ｃｓ、Ｃａ又はＢａであることを特徴とする上記［７］に記載の二環式アミン化合物の製造法。
Al a Mb P c O d (3)
[In the above formula (3), Al represents aluminum, M represents an alkali metal element or alkaline earth metal element, P represents phosphorus, and 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. ]
[8] The process for producing a bicyclic amine compound as described in [7] above, wherein in the formula (3), M is Na, K, Rb, Cs, Ca or Ba.
［９］上記式（３）において、ｂ／ａ＝０．０１〜０．２（モル比）、ｃ／ａ＝０．０１〜０．２（モル比）であることを特徴とする上記［７］又は［８］に記載の二環式アミン化合物の製造法。 [9] In the above formula (3), b / a = 0.01 to 0.2 (molar ratio) and c / a = 0.01 to 0.2 (molar ratio). [7] The process for producing a bicyclic amine compound according to [8].
［１０］固体触媒が、触媒担体として酸化アルミニウムを用いたものであることを特徴とする上記［１］乃至［９］のいずれかに記載の二環式アミン化合物の製造法。 [10] The method for producing a bicyclic amine compound as described in any one of [1] to [9] above, wherein the solid catalyst uses aluminum oxide as a catalyst carrier.
［１１］１次反応体中に含まれる、上記式（１）で示される化合物のモル量が、原料体に含まれる上記式（１）で示される化合物のモル量に対して、１〜５０％の範囲であることを特徴とする上記［１］乃至［１０］のいずれかに記載の二環式アミン化合物の製造法。 [11] The molar amount of the compound represented by the above formula (1) contained in the primary reactant is 1 to 50 with respect to the molar amount of the compound represented by the above formula (1) contained in the raw material body. %. The method for producing a bicyclic amine compound according to any one of [1] to [10] above, wherein
［１２］２次反応体中の、上記式（１）で示される化合物のモル量が、原料体に含まれる上記式（１）で示される化合物のモル量に対して、５％以下の範囲であることを特徴とする上記［１］乃至［１１］のいずれかに記載の二環式アミン化合物の製造法。 [12] The molar amount of the compound represented by the formula (1) in the secondary reactant is in the range of 5% or less with respect to the molar amount of the compound represented by the formula (1) contained in the raw material body. The method for producing a bicyclic amine compound according to any one of [1] to [11] above, wherein
本発明によれば、従来に比べて高い原料転化率で二環式アミン化合物を得ることができ、未反応原料の回収工程が不要となるため、製造時間の短縮、製造設備の簡略化に繋がることから、本発明は工業的に極めて有用である。 According to the present invention, a bicyclic amine compound can be obtained at a higher raw material conversion rate than in the prior art, and a recovery step for unreacted raw materials is not required, leading to shortened manufacturing time and simplified manufacturing equipment. Therefore, the present invention is extremely useful industrially.
また、本発明は、反応管閉塞の要因であるタールの生成量を低減させることができ、反応管の閉塞を遅延できる効果を有する。 In addition, the present invention can reduce the amount of tar that is a cause of reaction tube blockage, and has an effect of delaying the blockage of the reaction tube.
以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明の上記式（２）で示される二環式アミン化合物の製造法は、下記式（１）で示される化合物を含む原料体を気相中で固体触媒に接触させ１次反応体とする工程（Ａ）と、当該１次反応体を、気相中で当該固体触媒に接触させ２次反応体とする工程（Ｂ）とを含むことをその特徴とする。 In the method for producing a bicyclic amine compound represented by the above formula (2) of the present invention, a raw material containing a compound represented by the following formula (1) is contacted with a solid catalyst in a gas phase to form a primary reactant. It is characterized by comprising the step (A) and the step (B) in which the primary reactant is brought into contact with the solid catalyst in the gas phase to form a secondary reactant.
すなわち、本発明は、工程（Ｂ）で、上記式（１）で示される化合物及び上記式（２）で示される二環式アミン化合物の双方を含む１次反応体を、気相中で当該固体触媒に再度接触させ、残存する上記式（１）で示される化合物の転化を促進することで、原料である上記式（１）で示される化合物をほとんど含まない２次反応体とすることができる。 That is, the present invention provides a primary reactant containing both the compound represented by the above formula (1) and the bicyclic amine compound represented by the above formula (2) in the gas phase in the step (B). By contacting the solid catalyst again and promoting the conversion of the remaining compound represented by the formula (1), a secondary reactant containing almost no compound represented by the formula (1) as a raw material can be obtained. it can.
本発明において、１次反応体を、気相中で当該固体触媒に接触させる態様としては、特に限定するものではないが、例えば、下記式（１）で示される化合物を含む原料体を気相中で固体触媒に接触させた反応液を、当該固体触媒に再度接触させることが簡便であり、好ましい。 In the present invention, the embodiment in which the primary reactant is brought into contact with the solid catalyst in the gas phase is not particularly limited. For example, the raw material containing the compound represented by the following formula (1) is gas phase It is convenient and preferable that the reaction solution brought into contact with the solid catalyst is again brought into contact with the solid catalyst.
本発明の製造法において、上記式（１）で示される化合物は、上記式（２）で示される二環式アミン化合物の原料となる。 In the production method of the present invention, the compound represented by the above formula (1) is a raw material for the bicyclic amine compound represented by the above formula (2).
本発明において、上記式（１）における、Ｘは炭素原子又は窒素原子を表し、Ｙは水素原子、炭素数１〜４のアルキル基、水酸基、又は炭素数１〜４のヒドロキシアルキル基を表す。中でも入手のし易さ、及び取得コストの観点から、Ｙとしては水素原子、ヒドロキシメチル基、又はヒドロキシエチル基が好ましい。
本発明において、上記式（１）における、置換基Ｒ１〜Ｒ８は各々独立して、水素原子、炭素数１〜４のアルキル基（メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、イソブチル基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基）、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（メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓｅｃ−ブトキシ基）を表す。
中でも入手のし易さ、及び取得コストの観点から、上記式（１）及び式（２）は、Ｒ１〜Ｒ８が各々独立して、水素原子、メチル基、エチル基、イソプロピル基又はヒドロキシメチル基を表すこと（ただし、Ｒ１〜Ｒ８が全て同じ置換基になることはない。）が好ましく、上記式（１）及び式（２）において、Ｒ１〜Ｒ８が全て水素原子を表すことが最も好ましい。
In the present invention, in the above formula (1), X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. Among these, Y is preferably a hydrogen atom, a hydroxymethyl group, or a hydroxyethyl group from the viewpoint of easy availability and acquisition cost.
In the present invention, the substituents R1 to R8 in the above formula (1) are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms (methyl group, ethyl group, n-propyl group, isopropyl group, n- Butyl group, isobutyl group, sec-butyl group, tert-butyl group), hydroxyl group, hydroxymethyl group, or alkoxy group having 1 to 4 carbon atoms (methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n- Butoxy group, sec-butoxy group).
Above all, from the viewpoint of easy availability and acquisition cost, in the above formulas (1) and (2), R 1 to R 8 are each independently a hydrogen atom, a methyl group, an ethyl group, an isopropyl group or a hydroxy group. It is preferable to represent a methyl group (however, R 1 to R 8 are not all the same substituents), and in the above formulas (1) and (2), R 1 to R 8 are all hydrogen atoms. Most preferably it represents.
本発明において、上記式（１）で示される化合物のうち、Ｘが炭素原子である化合物の具体例としては、例えば、以下の例示化合物番号１〜４で示される化合物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。 In the present invention, among the compounds represented by the above formula (1), specific examples of the compound in which X is a carbon atom include compounds represented by the following exemplified compound numbers 1 to 4, The present invention is not limited to these.
本発明の製造法により製造される上記式（２）で示される二環式アミン化合物は、上記式（１）で示される化合物から得られるものである。 The bicyclic amine compound represented by the above formula (2) produced by the production method of the present invention is obtained from the compound represented by the above formula (1).
本発明において、上記式（２）における、Ｘは炭素原子又は窒素原子を表し、Ｙは水素原子、炭素数１〜４のアルキル基、水酸基、又は炭素数１〜４のヒドロキシアルキル基を表す。中でも入手のし易さ、及び取得コストの観点から、Ｙとしては水素原子、ヒドロキシメチル基、又はヒドロキシエチル基が好ましい。 In the present invention, in the above formula (2), X represents a carbon atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms. Among these, Y is preferably a hydrogen atom, a hydroxymethyl group, or a hydroxyethyl group from the viewpoint of easy availability and acquisition cost.
本発明において、上記式（２）における、置換基Ｒ１〜Ｒ８は各々独立して、水素原子、炭素数１〜４のアルキル基（メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、イソブチル基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基）、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（メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓｅｃ−ブトキシ基）を表す。
中でも原料の入手のし易さ、及び取得コストの観点から、上記式（２）は、Ｒ１〜Ｒ８が各々独立して、水素原子、メチル基、エチル基、イソプロピル基又はヒドロキシメチル基を表すこと（ただし、Ｒ１〜Ｒ８が全て同じ置換基になることはない。）が好ましく、上記式（２）において、Ｒ１〜Ｒ８が全て水素原子を表すことが最も好ましい。
In the present invention, the substituents R1 to R8 in the formula (2) are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms (methyl group, ethyl group, n-propyl group, isopropyl group, n- Butyl group, isobutyl group, sec-butyl group, tert-butyl group), hydroxyl group, hydroxymethyl group, or alkoxy group having 1 to 4 carbon atoms (methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n- Butoxy group, sec-butoxy group).
Above all, from the viewpoint of easy availability of raw materials and acquisition cost, in formula (2), R1 to R8 each independently represent a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, or a hydroxymethyl group. (However, R1 to R8 do not all become the same substituent.) In the above formula (2), it is most preferable that R1 to R8 all represent hydrogen atoms.
また、上記式（２）で示される二環式アミン化合物のうち、Ｘが炭素原子である化合物の具体例としては、例えば、以下の例示化合物番号１３〜１６で示される化合物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。 Moreover, as a specific example of the compound whose X is a carbon atom among the bicyclic amine compounds shown by said Formula (2), the compound shown by the following example compound numbers 13-16 can be mentioned, for example. However, the present invention is not limited to these.
本発明において、固体触媒としては、特に限定するものではないが、例えば、上記式（３）で示される無機化合物を用いることができる。固体触媒は調製のし易さ、及び取扱いの面から、触媒担体上に各成分を担持させたものとすることが好ましい。 In the present invention, the solid catalyst is not particularly limited. For example, an inorganic compound represented by the above formula (3) can be used. The solid catalyst is preferably prepared by supporting each component on a catalyst support from the viewpoint of ease of preparation and handling.
触媒担体としては、例えば、無機酸化物を用いることができ、無機酸化物としては、特に限定するものではないが、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、酸化ジルコニウムなどが挙げられる。これらの中でも、入手コスト、及び耐久性の観点から、酸化ケイ素、酸化アルミニウム、ハイシリカゼオライトが好ましく、酸化アルミニウムが最も好ましい。 As the catalyst carrier, for example, an inorganic oxide can be used, and the inorganic oxide is not particularly limited. For example, silicon oxide, aluminum oxide, aluminosilicate, zeolite, magnesium oxide, titanium oxide, oxidation Zirconium etc. are mentioned. Among these, silicon oxide, aluminum oxide, and high silica zeolite are preferable, and aluminum oxide is most preferable from the viewpoints of acquisition cost and durability.
本発明において、上記式（３）における、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、アルカリ金属元素又はアルカリ土類金属元素としては、例えば、Ｌｉ、Ｎａ、Ｋ、Ｒｂ、Ｃｓ、Ｃａ、Ｓｒ、Ｂａが挙げられる。これらの中ではＮａ、Ｋ、Ｒｂ、Ｃｓ、Ｃａ、Ｂａが好ましい。 In the present invention, M in the above formula (3) represents an alkali metal element or an alkaline earth metal element. Examples of the alkali metal element or alkaline earth metal element include Li, Na, K, Rb, Cs, and Ca. , Sr, and Ba. Among these, Na, K, Rb, Cs, Ca, and Ba are preferable.
本発明において、固体触媒におけるリン成分の原料としては特に限定するものではなく、例えば、リン酸、ホスホン酸、ホスフィン酸、ホスフィンオキサイド、各種リン酸塩等が挙げられる。これらの中ではリン酸アンモニウム塩が好ましい。 In the present invention, the raw material of the phosphorus component in the solid catalyst is not particularly limited, and examples thereof include phosphoric acid, phosphonic acid, phosphinic acid, phosphine oxide, and various phosphates. Of these, ammonium phosphate is preferable.
上記式（３）におけるａ、ｂ及びｃの値は、通常、ｂ／ａ＝０．００１〜０．３（モル比）、ｃ／ａ＝０．００１〜０．３（モル比）の範囲である。好ましくはｂ／ａ＝０．０１〜０．２（モル比）、ｃ／ａ＝０．０１〜０．２（モル比）の範囲である。この範囲とすることで固体触媒の酸塩基強度、比表面積等の物性を向上させ、触媒活性、選択率をより高めることができる。 The values of a, b and c in the above formula (3) are usually in the range of b / a = 0.001 to 0.3 (molar ratio) and c / a = 0.001 to 0.3 (molar ratio). It is. Preferably, b / a = 0.01 to 0.2 (molar ratio) and c / a = 0.01 to 0.2 (molar ratio). By setting it as this range, physical properties, such as acid-base intensity | strength of a solid catalyst, and a specific surface area, can be improved, and catalyst activity and a selectivity can be improved more.
本発明において、固体触媒の調製法は特に限定されるものではなく、一般的に行われる調製法が取られる。例えば、上記した固体触媒の原料（例えば、触媒担体、アルカリ金属元素成分又はアルカリ土類金属元素成分の原料、リン成分の原料等）を水中に溶解又は懸濁させて、攪拌、加熱、濃縮、乾燥後、成型し、更に焼成を経て固体触媒とする方法等が挙げられる。 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, the above-mentioned solid catalyst raw material (for example, catalyst carrier, alkali metal element component or alkaline earth metal element component raw material, phosphorus component raw material, etc.) is dissolved or suspended in water, stirred, heated, concentrated, Examples include a method of forming a solid catalyst after drying and then molding.
本発明において、上記式（１）で示される化合物を上記式（２）で示される二環式アミン化合物に変換させる反応工程は、特に限定するものではないが、気相中、固定床流通式で実施することが好ましい。 In the present invention, the reaction step for converting the compound represented by the above formula (1) into the bicyclic amine compound represented by the above formula (2) is not particularly limited. It is preferable to carry out.
本発明において、原料体は上記式（１）で示される化合物を含むものであればよく、上記式（２）で含む化合物をあえて含む必要はない。ただし、本発明の趣旨に反しない程度であれば、原料体が、上記式（１）で示される化合物以外の化合物を含有してもいても差し支えない。 In this invention, the raw material body should just contain the compound shown by the said Formula (1), and it is not necessary to dare to include the compound containing the said Formula (2). However, the raw material body may contain a compound other than the compound represented by the above formula (1) as long as it does not contradict the gist of the present invention.
本発明において、工程（Ａ）で用いる原料体としては、例えば、上記式（１）で示される化合物を希釈剤で希釈したものを用いることが好ましい。希釈剤としては、特に限定するものではないが、窒素ガス、水素ガス、アンモニアガス、水蒸気、炭化水素等の不活性ガスや、水、不活性な炭化水素等の不活性溶媒が挙げられ、これらのうち単独或は複数を用いて、原料を希釈し、反応を進行させることができる。これらの希釈剤は任意の量で使用でき、特に限定するものではないが、上記式（１）で示される化合物／希釈剤のモル比を０．００１〜１の範囲とすることが好ましい。モル比０．００１未満とすると、生産性が低下する恐れがあり、モル比１を超えると、選択性が低下する場合がある。希釈剤は、上記式（１）で示される化合物と同時に反応器内に導入してもよいし、予め上記式（１）で示される化合物を希釈剤混合させた後に、原料体として反応器に導入してもよい。 In the present invention, as the raw material body used in the step (A), for example, a material obtained by diluting the compound represented by the above formula (1) with a diluent is preferably used. Examples of the diluent include, but are not limited to, inert gases such as nitrogen gas, hydrogen gas, ammonia gas, water vapor, and hydrocarbons, and inert solvents such as water and inert hydrocarbons. One or more of them can be used to dilute the raw material and allow the reaction to proceed. These diluents can be used in any amount and are not particularly limited. However, the compound / diluent molar ratio represented by the above formula (1) is preferably in the range of 0.001 to 1. If the molar ratio is less than 0.001, the productivity may decrease. If the molar ratio exceeds 1, the selectivity may decrease. The diluent may be introduced into the reactor at the same time as the compound represented by the above formula (1), or after the compound represented by the above formula (1) is mixed with the diluent in advance, the raw material is introduced into the reactor. It may be introduced.
工程（Ａ）で得られる１次反応体には、未反応の上記式（１）で示される化合物、及び固体触媒の作用により分子内脱水した上記式（２）で示される二環式アミン化合物が含まれる。１次反応体中に含まれる、上記式（１）で示される化合物のモル量は、特に限定するものではないが、原料体に含まれる上記式（１）で示される化合物のモル量に対して１〜５０％の範囲であることが好ましい。１％未満の場合、そもそも工程（Ｂ）を実施する必要はなく、５０％を超えると工程（Ｂ）を実施しても、残存する上記式（１）で示される化合物を十分に転化できない場合がある。１次反応体中に含まれる、上記式（１）で示される化合物のモル量が上記範囲に収まらない場合、反応温度、触媒層への滞在時間等の反応条件を調整し範囲内へ収めることが好ましい。 The primary reactant obtained in the step (A) includes an unreacted compound represented by the above formula (1) and a bicyclic amine compound represented by the above formula (2) dehydrated intramolecularly by the action of a solid catalyst. Is included. The molar amount of the compound represented by the above formula (1) contained in the primary reactant is not particularly limited, but relative to the molar amount of the compound represented by the above formula (1) contained in the raw material body. Is preferably in the range of 1 to 50%. If it is less than 1%, it is not necessary to carry out step (B) in the first place. If it exceeds 50%, the remaining compound represented by formula (1) cannot be sufficiently converted even if step (B) is carried out. There is. When the molar amount of the compound represented by the above formula (1) contained in the primary reactant does not fall within the above range, the reaction conditions such as the reaction temperature and the residence time in the catalyst layer are adjusted to fall within the range. Is preferred.
本発明において、工程（Ｂ）で使用する１次反応体は、上記と同様に希釈剤で希釈して反応に用いることができ、希釈剤としても上記と同様のものを用いることができる。 In the present invention, the primary reactant used in step (B) can be used in the reaction after being diluted with a diluent in the same manner as described above, and the same diluent as described above can be used.
本発明において、工程（Ｂ）で得られる２次反応体には、未反応の上記式（１）で示される化合物、及び固体触媒の作用により分子内脱水した上記式（２）で示される二環式アミン化合物が含まれる。２次反応体中に含まれる、上記式（１）で示される化合物のモル量は、特に限定するものではないが、原料体に含まれる上記式（１）で示される化合物のモル量に対して０〜５％の範囲であることが好ましい。５％を超えると経済的観点から、原料の回収工程が必要となる恐れがある。 In the present invention, the secondary reactant obtained in the step (B) includes an unreacted compound represented by the above formula (1) and a compound represented by the above formula (2) dehydrated intramolecularly by the action of a solid catalyst. Cyclic amine compounds are included. The molar amount of the compound represented by the above formula (1) contained in the secondary reactant is not particularly limited, but relative to the molar amount of the compound represented by the above formula (1) contained in the raw material body. Is preferably in the range of 0 to 5%. If it exceeds 5%, a raw material recovery step may be required from an economic viewpoint.
本発明においては、工程（Ａ）、工程（Ｂ）以外の工程を追加して実施しても一向に差し支えない。例えば、２次反応体を再度、気相中で固体触媒に接触させ、３次反応体とする工程、３次反応体を再度、気相中で固体触媒に接触させ、４次反応体とする工程、冷却工程、加熱工程、洗浄工程、抽出工程、超音波処理工程、蒸留工程、その他薬液で処理する工程などを適宜実施することができる。 In this invention, even if it implements by adding processes other than a process (A) and a process (B), it does not interfere. For example, the step in which the secondary reactant is again brought into contact with the solid catalyst in the gas phase to obtain a tertiary reactant, and the tertiary reactant is again brought into contact with the solid catalyst in the gas phase to obtain a quaternary reactant. A process, a cooling process, a heating process, a washing process, an extraction process, an ultrasonic treatment process, a distillation process, other processes with chemicals, and the like can be appropriately performed.
本発明において、工程（Ａ）及び工程（Ｂ）を含む反応工程は、３００〜５００℃の温度範囲で実施することが好ましく、さらに３５０〜４５０℃の温度範囲で実施することが好ましい。３００℃未満でも反応は進行するが、十分な反応速度が得られない場合あり、温度を下げる利点は少ない。また５００℃を越える温度で反応させると原料及び生成物が分解する恐れがあり、上記式（２）で示される二環式アミン化合物の選択率が低下することがある。また、工程（Ａ）と工程（Ｂ）の反応温度は異なっても何ら差し支えない。 In this invention, it is preferable to implement the reaction process including a process (A) and a process (B) in the temperature range of 300-500 degreeC, and also it is preferable to implement in the temperature range of 350-450 degreeC. Although the reaction proceeds even below 300 ° C., a sufficient reaction rate may not be obtained, and there are few advantages of lowering the temperature. Moreover, when it is made to react at the temperature exceeding 500 degreeC, there exists a possibility that a raw material and a product may decompose | disassemble, and the selectivity of the bicyclic amine compound shown by the said Formula (2) may fall. In addition, the reaction temperatures of the step (A) and the step (B) may be different from each other.
また、本発明の製造法において、反応は、０．１〜５０ＭＰａの圧力範囲で実施することが好ましく、さらに１〜５ＭＰａの圧力範囲で実施することが好ましい。０．１ＭＰａ未満でも反応は進行するが、単位時間あたりの生産量が低下し、圧力を下げる利点は少ない。また５０ＭＰａを越える圧力で反応させても、特別な効果はなく、安全面で工業的に不利となる。 Moreover, in the manufacturing method of this invention, it is preferable to implement reaction in the pressure range of 0.1-50 MPa, and also it is preferable to implement in the pressure range of 1-5 MPa. Although the reaction proceeds even at less than 0.1 MPa, the production amount per unit time decreases, and there are few advantages of lowering the pressure. Moreover, even if it reacts with the pressure exceeding 50 MPa, there is no special effect and it becomes industrially disadvantageous in terms of safety.
本発明において、工程（Ｂ）で得られた２次反応体は、後工程の精製工程で精製され、上記式（２）で示される二環式アミン化合物とすることが好ましい。精製工程で精製する方法としては、一般に知られている方法を実施することができ、上記式（２）で示される二環式アミン化合物の精製方法としては、例えば、再結晶や蒸留によって精製する方法が挙げられるが、その他どの様な方法を使用しても一向に差し支えない。 In the present invention, the secondary reactant obtained in the step (B) is preferably purified in a subsequent purification step to be a bicyclic amine compound represented by the above formula (2). As a purification method in the purification step, a generally known method can be carried out. As a purification method of the bicyclic amine compound represented by the above formula (2), for example, purification is performed by recrystallization or distillation. There is a method, but any other method can be used.
本発明を以下の実施例により更に詳細に説明するが、本発明はこれらに限定して解釈されるものではない。 The present invention will be described in more detail with reference to the following examples, but the present invention should not be construed as being limited thereto.
なお、本実施例における生成物の収率、選択率は、ガスクロマトグラフィーで確認した。 The yield and selectivity of the product in this example were confirmed by gas chromatography.
ガスクロマトグラフィーには、ガスクロマトグラフ（島津製作所製 ＧＣ−２０１４）、キャピラリーカラム（Ｊ＆Ｗ Ｓｃｉｅｎｔｉｆｉｃ社製 ＤＢ−５）、及び検出器（ＦＩＤ）を使用した。 A gas chromatograph (Shimadzu GC-2014), a capillary column (J & W Scientific DB-5), and a detector (FID) were used for gas chromatography.
また、以下の実施例における評価において、２次反応体の転化率、選択率、及び収率はいずれも１次反応体を製造するために用いた原料使用量を基準に、２工程トータルの値として算出した。 Further, in the evaluation in the following examples, the conversion rate, selectivity, and yield of the secondary reactant are all values of the two steps based on the amount of raw material used to produce the primary reactant. Calculated as
参考例１ Ｎ−（２，３−ジヒドロキシプロピル）ピペラジンの合成．
２００ｍｌの三口フラスコに、ピペラジン８６．１ｇ（１．０モル）、溶媒としてメタノール１００ｍｌを仕込み、窒素雰囲気下でグリシドール２２．２ｇ（０．３モル）を４時間かけて滴下した。三口フラスコをオイルバス中に保持することで、反応体の温度を６０℃に保った。グリシドールの滴下終了後、単蒸留により反応体中の溶媒であるメタノール、未反応のピペラジンを留去した。生成物を真空乾燥することで、Ｎ−（２，３−ジヒドロキシプロピル）ピペラジン（例示化合物番号７で示される化合物）４５．２ｇを得た。
Reference 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 reactant was kept at 60 ° C. by holding the three-necked flask in an oil bath. After completion of dropwise addition of glycidol, methanol and unreacted piperazine as the solvent in the reactant were distilled off by simple distillation. The product was vacuum-dried to obtain 45.2 g of N- (2,3-dihydroxypropyl) piperazine (a compound represented by Exemplified Compound No. 7).
参考例２ 触媒Ａの調製．
触媒担体としてα型酸化アルミニウム粉末（キシダ化学製）７．２ｇを水１００ｍｌと混合しスラリー溶液とし、硝酸カリウム３．４ｇ、リン酸水素二アンモニウム２．７ｇを混合し分散させた後、エバポレーター用いて蒸発乾固させ白色固体を得た。この固体を圧縮成型し、窒素雰囲気の下マッフル炉で６００℃、４時間焼成し、３．５メッシュに破砕して気相反応用触媒［上記式（３）において、Ｍ＝Ｋ、ａ＝１、ｂ＝０．１、ｃ＝０．０６。以下、触媒Ａと称する。］を得た。
Reference Example 2 Preparation of catalyst A.
As a catalyst carrier, 7.2 g of α-type aluminum oxide powder (manufactured by Kishida Chemical Co., Ltd.) is mixed with 100 ml of water to form a slurry solution. Evaporation to dryness gave a white solid. This solid is compression-molded, calcined in a muffle furnace under a nitrogen atmosphere at 600 ° C. for 4 hours, crushed to 3.5 mesh, and a gas phase reaction catalyst [in the above formula (3), M = K, a = 1, b = 0.1, c = 0.06. Hereinafter, it is referred to as catalyst A. ] Was obtained.
参考例３ 触媒Ｂの調製．
参考例２において、硝酸カリウムの替わりに硝酸ルビジウム４．９ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｒｂ、ａ＝１、ｂ＝０．１、ｃ＝０．０６。以下、触媒Ｂと称する。］を得た。
Reference Example 3 Preparation of catalyst B.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 4.9 g of rubidium nitrate was used instead of potassium nitrate, and a catalyst for gas phase reaction [in the above formula (3), M = Rb, a = 1 , B = 0.1, c = 0.06. Hereinafter, it is referred to as catalyst B. ] Was obtained.
参考例４ 触媒Ｃの調製．
参考例２において、硝酸カリウムの替わりに硝酸セシウム６．５ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｃｓ、ａ＝１、ｂ＝０．１、ｃ＝０．０６。以下、触媒Ｃと称する。］を得た。
Reference Example 4 Preparation of catalyst C.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 6.5 g of cesium nitrate was used instead of potassium nitrate, and a catalyst for gas phase reaction [in the above formula (3), M = Cs, a = 1 , B = 0.1, c = 0.06. Hereinafter, it is referred to as catalyst C. ] Was obtained.
参考例５ 触媒Ｄの調製．
参考例２において、硝酸カリウムの替わりに硝酸カルシウム５．５ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｃａ、ａ＝１、ｂ＝０．１、ｃ＝０．０６。以下、触媒Ｄと称する。］を得た。
Reference Example 5 Preparation of catalyst D.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 5.5 g of calcium nitrate was used instead of potassium nitrate, and a catalyst for gas phase reaction [in the above formula (3), M = Ca, a = 1 , B = 0.1, c = 0.06. Hereinafter, it is referred to as catalyst D. ] Was obtained.
参考例６ 触媒Ｅの調製．
参考例２において、硝酸カリウムの替わりに硝酸バリウム８．７ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｂａ、ａ＝１、ｂ＝０．１、ｃ＝０．０６。以下、触媒Ｅと称する。］を得た。
Reference Example 6 Preparation of catalyst E.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 8.7 g of barium nitrate was used instead of potassium nitrate, and a catalyst for gas phase reaction [in the above formula (3), M = Ba, a = 1 , B = 0.1, c = 0.06. Hereinafter, it is referred to as catalyst E. ] Was obtained.
参考例７ 触媒Ｆの調製．
参考例２において、硝酸カリウムの替わりに硝酸セシウム１．３ｇ、リン酸水素二アンモニウム０．５４ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｃｓ、ａ＝１、ｂ＝０．０２、ｃ＝０．０１２。以下、触媒Ｆと称する。］を得た。
Reference Example 7 Preparation of catalyst F.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 1.3 g of cesium nitrate and 0.54 g of diammonium hydrogen phosphate were used instead of potassium nitrate, and a catalyst for gas phase reaction [the above formula (3) , M = Cs, a = 1, b = 0.02, c = 0.012. Hereinafter, it is referred to as catalyst F. ] Was obtained.
参考例８ 触媒Ｇの調製．
参考例２において、硝酸カリウムの替わりに硝酸セシウム１３ｇ、リン酸水素二アンモニウム５．４ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｃｓ、ａ＝１、ｂ＝０．２、ｃ＝０．１２。以下、触媒Ｇと称する。］を得た。
Reference Example 8 Preparation of catalyst G.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 13 g of cesium nitrate and 5.4 g of diammonium hydrogen phosphate were used instead of potassium nitrate, and a catalyst for gas phase reaction [in the above formula (3), M = Cs, a = 1, b = 0.2, c = 0.12. Hereinafter, it is referred to as catalyst G. ] Was obtained.
参考例８ 触媒Ｈの調製．
参考例２において、硝酸カリウムの替わりに硝酸セシウム３２．５ｇ、リン酸水素二アンモニウム１３．５ｇを用いる以外は、参考例２に記載の方法に従い触媒調製し、気相反応用触媒［上記式（３）において、Ｍ＝Ｃｓ、ａ＝１、ｂ＝０．５、ｃ＝０．３。本発明範囲外。以下、触媒Ｇと称する。］を得た。
Reference Example 8 Preparation of catalyst H.
In Reference Example 2, a catalyst was prepared according to the method described in Reference Example 2 except that 32.5 g of cesium nitrate and 13.5 g of diammonium hydrogen phosphate were used instead of potassium nitrate, and a catalyst for gas phase reaction [the above formula (3) , M = Cs, a = 1, b = 0.5, c = 0.3. Outside the scope of the present invention. Hereinafter, it is referred to as catalyst G. ] Was obtained.
実施例１ 触媒Ａを用いた例示化合物番号１７で示される化合物の合成．
例示化合物番号５で示される化合物［１−（２−ヒドロキシエチル）ピペラジン、東京化成社製］を水に溶解させ、１０重量％水溶液の原料体を調製した。直径１５ｍｍの石英反応管に、触媒Ａを２０ｍｌ、その上下部にそれぞれ長さ２３ｃｍになるように、セラミックス製ラシヒリング（直径３ｍｍ×長さ３ｍｍ×厚み１ｍｍ）を詰めた。触媒層の温度は３８０℃に保ち、上部より、上記の調製した原料体を０．３ｇ／分の速度で１２時間滴下した。得られた反応混合ガスをコンデンサーで冷却し、１次反応体２１５ｇを得た。１次反応体をガスクロマトグラフィーで分析した結果、例示化合物番号５で示される化合物の転化率は６２％であった。
Example 1 Synthesis of compound represented by Exemplified Compound No. 17 using Catalyst A.
A compound [1- (2-hydroxyethyl) piperazine, manufactured by Tokyo Chemical Industry Co., Ltd.] represented by Exemplified Compound No. 5 was dissolved in water to prepare a 10 wt% aqueous solution raw material. A quartz reaction tube having a diameter of 15 mm was packed with ceramic Raschig rings (diameter 3 mm × length 3 mm × thickness 1 mm) so that the catalyst A was 20 ml and the upper and lower portions thereof had a length of 23 cm. The temperature of the catalyst layer was maintained at 380 ° C., and the prepared raw material was dropped from the top at a rate of 0.3 g / min for 12 hours. The obtained reaction mixed gas was cooled with a condenser to obtain 215 g of a primary reactant. As a result of analyzing the primary reactant by gas chromatography, the conversion of the compound represented by Example Compound No. 5 was 62%.
得られた１次反応体を、触媒層の温度を４００℃とする以外は上記と同様の条件で全量反応管内に滴下し、２次反応体２１３ｇを得た。２次反応体をガスクロマトグラフィーで分析した結果、例示化合物番号５で示される化合物の転化率は９６％、例示化合物番号１７で示される化合物への選択率は４４％、トータルの収率は４２％であった。結果は他の実施例と共に表１に示す。 The total amount of the obtained primary reactant was dropped into the reaction tube under the same conditions as described above except that the temperature of the catalyst layer was 400 ° C. to obtain 213 g of a secondary reactant. As a result of analyzing the secondary reactant by gas chromatography, the conversion rate of the compound represented by Example Compound No. 5 was 96%, the selectivity to the compound represented by Example Compound No. 17 was 44%, and the total yield was 42 %Met. The results are shown in Table 1 together with other examples.
触媒Ａに替え触媒Ｂを用い、１次反応体から２次反応体を得る際の触媒層の温度を３８０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に併せて示す。
The secondary reactant is obtained by performing the same operation as described in Example 1 except that the catalyst B is used instead of the catalyst A, and the temperature of the catalyst layer when the secondary reactant is obtained from the primary reactant is 380 ° C. Got. The results are also shown in Table 1.
実施例３ 触媒Ｃを用いた例示化合物番号１７で示される化合物の合成．
触媒Ａに替え触媒Ｃを用い、１次反応体から２次反応体を得る際の触媒層の温度を３８０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に併せて示す。
Example 3 Synthesis of compound represented by Exemplified Compound No. 17 using Catalyst C
The secondary reactant is obtained by performing the same operation as described in Example 1 except that the catalyst C is used instead of the catalyst A, and the temperature of the catalyst layer when the secondary reactant is obtained from the primary reactant is 380 ° C. Got. The results are also shown in Table 1.
実施例４ 触媒Ｄを用いた例示化合物番号１７で示される化合物の合成．
触媒Ａに替え触媒Ｄを用い、１次反応体から２次反応体を得る際の触媒層の温度を３９０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に併せて示す。
Example 4 Synthesis of compound represented by Exemplified Compound No. 17 using Catalyst D.
The secondary reactant is obtained by performing the same operation as described in Example 1 except that the catalyst D is used instead of the catalyst A, and the temperature of the catalyst layer when the secondary reactant is obtained from the primary reactant is 390 ° C. Got. The results are also shown in Table 1.
実施例５ 触媒Ｅを用いた例示化合物番号１７で示される化合物の合成．
触媒Ａに替え触媒Ｅを用い、１次反応体から２次反応体を得る際の触媒層の温度を３９０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に併せて示す。
Example 5 Synthesis of compound represented by Exemplified Compound No. 17 using Catalyst E.
The secondary reactant is obtained by performing the same operation as described in Example 1 except that the catalyst E is used instead of the catalyst A, and the temperature of the catalyst layer when the secondary reactant is obtained from the primary reactant is 390 ° C. Got. The results are also shown in Table 1.
実施例６ 触媒Ｃを用いた例示化合物番号１３で示される化合物の合成．
触媒Ａに替え触媒Ｃ、例示化合物番号５で示される化合物の替わりに例示化合物番号１で示される化合物［４−（２−ヒドロキシエチル）ピペリジン、東京化成社製］を用い、１次反応体から２次反応体を得る際の触媒層の温度を３８０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に示す。
Example 6 Synthesis of compound represented by Exemplified Compound No. 13 using Catalyst C.
In place of the catalyst A, instead of the catalyst C and the compound represented by the exemplified compound number 5, the compound represented by the exemplified compound number 1 [4- (2-hydroxyethyl) piperidine, manufactured by Tokyo Chemical Industry Co., Ltd.] was used. A secondary reactant was obtained by performing the same operation as in the method described in Example 1 except that the temperature of the catalyst layer when obtaining the secondary reactant was 380 ° C. The results are shown in Table 1.
実施例７ 触媒Ｆを用いた例示化合物番号１３で示される化合物の合成．
触媒Ａに替え触媒Ｆ、例示化合物番号５で示される化合物の替わりに、例示化合物番号１で示される化合物［４−（２−ヒドロキシエチル）ピペリジン、東京化成社製］を用い、原料体から１次反応体を得る際の触媒層の温度を３９０℃、１次反応体から２次反応体を得る際の触媒層の温度を４２０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に示す。
Example 7 Synthesis of compound represented by Exemplified Compound No. 13 using Catalyst F.
In place of the catalyst A instead of the catalyst F, the compound represented by Exemplified Compound No. 5 is replaced with the compound [4- (2-hydroxyethyl) piperidine, manufactured by Tokyo Chemical Industry Co., Ltd.] represented by Exemplified Compound No. 1 Operation similar to the method described in Example 1 except that the temperature of the catalyst layer when obtaining the secondary reactant is 390 ° C. and the temperature of the catalyst layer when obtaining the secondary reactant from the primary reactant is 420 ° C. To obtain a secondary reactant. The results are shown in Table 1.
実施例８．触媒Ｃを用いた例示化合物番号１９で示される化合物の合成．
触媒Ａに替え触媒Ｃ、例示化合物番号５で示される化合物の替わりに、参考例１で調製した例示化合物番号７で示される化合物を用い、１次反応体から２次反応体を得る際の触媒層の温度を３８０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に併せて示す。
Example 8 FIG. Synthesis of compound represented by Exemplified Compound No. 19 using Catalyst C.
Catalyst for obtaining secondary reactant from primary reactant using catalyst C instead of catalyst A, compound shown by example compound number 7 prepared in Reference Example 1 instead of compound shown by example compound number 5 A secondary reactant was obtained in the same manner as in Example 1 except that the temperature of the layer was 380 ° C. The results are also shown in Table 1.
実施例９ 触媒Ｇを用いた例示化合物番号１９で示される化合物の合成．
触媒Ａに替え触媒Ｇ、例示化合物番号５で示される化合物の替わりに、参考例１で調製した例示化合物番号７で示される化合物を用い、原料体から１次反応体を得る際の触媒層の温度を３７０℃、１次反応体から２次反応体を得る際の触媒層の温度を３６０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表１に示す。
Example 9 Synthesis of compound represented by Exemplified Compound No. 19 using Catalyst G
In place of the catalyst A instead of the catalyst G and the compound represented by Exemplified Compound No. 5, the compound represented by Exemplified Compound No. 7 prepared in Reference Example 1 was used to obtain the primary reactant from the raw material. A secondary reactant was obtained by performing the same operation as in Example 1 except that the temperature of the catalyst layer at the time of obtaining the secondary reactant from the primary reactant was 370 ° C and the temperature of the catalyst layer was 360 ° C. The results are shown in Table 1.
比較例１ 触媒Ｃを用いた例示化合物番号１７で示される化合物の合成．
触媒Ａに替え触媒Ｃ、原料体から１次反応体を得る際の触媒層の温度を４４０℃とし、１次反応体から２次反応体を得る工程（Ｂ）を実施しないこと以外は実施例１に記載の方法と同様の操作を行い１次反応体を得た。結果を表２に示す。
Comparative Example 1 Synthesis of compound represented by Exemplified Compound No. 17 using Catalyst C.
Example except that the temperature of the catalyst layer when the primary reactant is obtained from the catalyst C and the raw material body is changed to 440 ° C. instead of the catalyst A, and the step (B) for obtaining the secondary reactant from the primary reactant is not performed. The same operation as described in 1 was performed to obtain a primary reactant. The results are shown in Table 2.
触媒Ａに替え触媒Ｈ、例示化合物番号５で示される化合物の替わりに、例示化合物番号１で示される化合物［４−（２−ヒドロキシエチル）ピペリジン、東京化成社製］を用い、１次反応体から２次反応体を得る際の触媒層の温度を３８０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表２に示す。
Instead of the catalyst A instead of the catalyst A and the compound represented by the exemplified compound number 5, the compound [4- (2-hydroxyethyl) piperidine, manufactured by Tokyo Chemical Industry Co., Ltd.] represented by the exemplified compound number 1 is used as the primary reactant. The secondary reactant was obtained by performing the same operation as described in Example 1 except that the temperature of the catalyst layer when obtaining the secondary reactant was from 380 ° C. The results are shown in Table 2.
参考例９ 触媒Ｃを用いた例示化合物番号１９で示される化合物の合成
触媒Ａに替え触媒Ｃ、例示化合物番号５で示される化合物の替わりに、参考例１で調製した例示化合物番号７で示される化合物を用い、原料体から１次反応体を得る際の触媒層の温度を３５０℃、１次反応体から２次反応体を得る際の触媒層の温度を３５０℃とする以外は実施例１に記載の方法と同様の操作を行い２次反応体を得た。結果を表２に併せて示す。
Reference Example 9 Synthesis of Compound Represented by Exemplified Compound No. 19 Using Catalyst C In place of Catalyst A and Compound represented by Exemplified Compound No. 5 instead of Catalyst A, it is represented by Exemplified Compound No. 7 prepared in Reference Example 1. Example 1 except that the temperature of the catalyst layer at the time of obtaining the primary reactant from the raw material body is 350 ° C., and the temperature of the catalyst layer at the time of obtaining the secondary reactant from the primary reactant is 350 ° C. The secondary reaction product was obtained by the same operation as described in 1. The results are also shown in Table 2.
表１に示したとおり、実施例では、原料化合物の転化率がいずれも９５％以上となったことから、本発明が原料回収工程を必要としないプロセスであることが分かる。 As shown in Table 1, in the examples, since the conversion rate of the raw material compounds was 95% or more, it is understood that the present invention is a process that does not require the raw material recovery step.
一方、表２に示したとおり、比較例１のように反応温度を高め、転化率を向上させる方法では、選択率が低下し、収率が大きく低下した。 On the other hand, as shown in Table 2, in the method of increasing the reaction temperature and improving the conversion rate as in Comparative Example 1, the selectivity decreased and the yield decreased greatly.
また、比較例２のように、触媒担持成分を本発明の範囲外まで増やし触媒活性を高めた方法でも同様に、選択率が低下し、収率が低下する結果となった。 In addition, as in Comparative Example 2, the method of increasing the catalyst supporting component outside the range of the present invention and increasing the catalytic activity also resulted in a decrease in selectivity and a decrease in yield.
なお、参考例９のように、１次反応体の転化率が本発明の好ましい範囲を大きく逸脱している場合は、再度触媒層を通し２次反応体としても転化率が不十分となる場合があることが分かる。 When the conversion rate of the primary reactant greatly deviates from the preferred range of the present invention as in Reference Example 9, the conversion rate is insufficient even as a secondary reactant through the catalyst layer again. I understand that there is.
以上の結果から、本発明は、原料の転化率を著しく向上でき、未反応原料の回収工程が不要な二環式アミン化合物の製造法であることが理解される。 From the above results, it is understood that the present invention is a method for producing a bicyclic amine compound that can significantly improve the conversion rate of raw materials and does not require a step of recovering unreacted raw materials.
Claims (12)
ＡｌａＭｂＰｃＯｄ （３）
［上記式（３）中、Ａｌはアルミニウムを表し、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。］ The method for producing a bicyclic amine compound according to any one of claims 1 to 6, wherein an inorganic oxide represented by the following formula (3) is used as the solid catalyst.
Al a Mb P c O d (3)
[In the above formula (3), Al represents aluminum, M represents an alkali metal element or alkaline earth metal element, P represents phosphorus, and 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. ]
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| CN104557947A (en) * | 2014-12-23 | 2015-04-29 | 绍兴兴欣化工有限公司 | Method of producing 2-hydroxymethyl triethylenediamine continuously |
| JP2016199471A (en) * | 2015-04-07 | 2016-12-01 | 東ソー株式会社 | Method of producing bicyclic amine compound |
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| CN104557947A (en) * | 2014-12-23 | 2015-04-29 | 绍兴兴欣化工有限公司 | Method of producing 2-hydroxymethyl triethylenediamine continuously |
| JP2016199471A (en) * | 2015-04-07 | 2016-12-01 | 東ソー株式会社 | Method of producing bicyclic amine compound |
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