JP6273389B1 - Method for producing N-aliphatic substituted maleimide compound - Google Patents

Abstract

【課題】穏和な条件下、簡便な操作で、目的とするＮ−脂肪族置換マレイミド化合物を副生物の生成を抑制して高選択的に効率よく、好収率で得ることができるＮ−脂肪族置換マレイミド化合物の製造方法の提供。【解決手段】無水マレイン酸と、酸触媒と、脱水助触媒として該酸触媒に対し０．１５〜０．８モル当量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、式（１）で表される脂肪族第一級アミン化合物又はその溶液を供給し、均一反応系で脱水環化させる、式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法。（Ｒはｎ価の脂肪族炭化水素基；ｎは１〜６の整数）【選択図】なし[PROBLEMS] To obtain a desired N-aliphatic substituted maleimide compound by a simple operation under mild conditions while suppressing the formation of by-products with high selectivity and good yield. Of a method for producing a group-substituted maleimide compound. SOLUTION: Contains maleic anhydride, an acid catalyst, 0.15-0.8 molar equivalent of a tertiary amine compound with respect to the acid catalyst as a dehydration cocatalyst, and an organic solvent azeotropic with water. An N-fat represented by the formula (2) is supplied with the aliphatic primary amine compound represented by the formula (1) or a solution thereof under heating and reflux and subjected to dehydration cyclization in a homogeneous reaction system. Of a group-substituted maleimide compound. (R is an n-valent aliphatic hydrocarbon group; n is an integer of 1 to 6) [Selection] None

Description

本発明は、Ｎ−脂肪族置換マレイミド化合物の製造方法に関するものである。   The present invention relates to a method for producing an N-aliphatic substituted maleimide compound.

Ｎ−脂肪族置換マレイミド化合物は、耐熱性樹脂のモノマー、医農薬中間体として有用な化合物群であり、これまで種々の製造方法が検討されている。   N-aliphatic substituted maleimide compounds are a group of compounds useful as monomers of heat-resistant resins and intermediates for medicines and agricultural chemicals, and various production methods have been studied so far.

一般的な方法としては、第一級アミンと無水マレイン酸とを反応させて得られるマレアミド酸を脱水環化する方法がある。
特に窒素上の置換基が芳香族基である場合には、マレアミド酸の脱水環化を無水酢酸等の脱水剤存在下に行う方法（特許文献１）、酸触媒および非プロトン性極性溶媒存在下に共沸脱水環化を行う方法（特許文献２）、オルトリン酸およびアニリンを珪藻土に担持させたものを不均一触媒として用い共沸脱水環化を行う方法（特許文献３）等が知られている。 As a general method, there is a method in which maleamic acid obtained by reacting a primary amine and maleic anhydride is subjected to dehydration cyclization.
In particular, when the substituent on nitrogen is an aromatic group, maleamide acid is cyclized in the presence of a dehydrating agent such as acetic anhydride (Patent Document 1), in the presence of an acid catalyst and an aprotic polar solvent. There are known methods for carrying out azeotropic dehydration cyclization (Patent Document 2), methods for carrying out azeotropic dehydration cyclization using orthophosphoric acid and aniline supported on diatomaceous earth as a heterogeneous catalyst (Patent Document 3), etc. Yes.

一方、窒素上の置換基が脂肪族基である場合、窒素上の置換基が芳香族基であるものと比較して、前駆体であるマレアミド酸が、脱水環化の反応性に乏しい。また、脂肪族基である場合、異性化しフマルアミド酸となることにより脱水環化が進行せず、加水分解や分子間脱水等の副反応を起こしやすい。そのため、Ｎ−芳香族置換マレイミド類の製造方法と同様の方法では効率よく目的物を得ることは難しく、これらの方法をＮ−脂肪族置換マレイミド化合物の製造方法に適用することには困難性がある。   On the other hand, when the substituent on nitrogen is an aliphatic group, the maleamic acid which is a precursor is poor in the reactivity of dehydration cyclization compared with the substituent on nitrogen which is an aromatic group. In the case of an aliphatic group, isomerization to fumaramic acid does not proceed with dehydration cyclization, and side reactions such as hydrolysis and intermolecular dehydration are likely to occur. Therefore, it is difficult to efficiently obtain the target product by a method similar to the method for producing N-aromatic substituted maleimides, and it is difficult to apply these methods to the method for producing N-aliphatic substituted maleimide compounds. is there.

Ｎ−脂肪族置換マレイミド化合物の製造方法としては、各種の検討がなされている。
例えば、スルホン酸、ならびに、酢酸等のプロトン性極性溶媒および非極性溶媒存在下、第一級アミンを滴下することにより、順次共沸脱水環化させる方法（特許文献４）、亜リン酸モノアミン塩水溶液を触媒として、マレアミド酸を過加熱水蒸気を用いて脱水環化させる方法（特許文献５）、ブレンステッド酸および該ブレンステッド酸に対し０．０５〜０．５当量の有機アミンを不均一系触媒として、マレアミド酸を共沸脱水環化させる方法（特許文献６）、酸と第三級アミンや第四級アンモニウム塩等のオニウム塩を触媒として、マレアミド酸を共沸脱水環化させる方法（特許文献７）が挙げられる。 Various studies have been made on methods for producing N-aliphatic substituted maleimide compounds.
For example, a sulfonic acid, a method in which a primary amine is dropped in the presence of a protic polar solvent such as acetic acid and a nonpolar solvent, and then azeotropic dehydration cyclization (Patent Document 4), phosphorous acid monoamine salt Method of dehydrating cyclization of maleamic acid using superheated steam using aqueous solution as catalyst (Patent Document 5), heterogeneous system of Bronsted acid and 0.05 to 0.5 equivalent of organic amine with respect to Bronsted acid A method of azeotropic dehydration cyclization of maleamic acid as a catalyst (Patent Document 6), A method of azeotropic dehydration cyclization of maleamic acid using an acid and an onium salt such as a tertiary amine or quaternary ammonium salt ( Patent document 7) is mentioned.

米国特許第２４４４５３６号明細書U.S. Pat. No. 2,444,536 特開昭５３−６８７７０号公報JP-A-53-68770 特開平５−２１３８６９号公報JP-A-5-213869 特開平１０−５９９３５号公報Japanese Patent Laid-Open No. 10-59935 特開平６−１８４１００号公報JP-A-6-184100 特開昭６３−１９６５６０号公報JP-A-63-196560 特開昭６２−１３８４６７号公報Japanese Patent Laid-Open No. 62-138467

しかし、上記特許文献５〜７記載のＮ−脂肪族置換マレイミド化合物の製造方法には下記の問題点があった。
特許文献５記載の製造方法では、高圧を要し特殊な反応設備を使用するため、簡便で一般的な操作とは言い難い。
特許文献６では、実施例は、ブレンステッド酸としてリン酸系酸触媒、かつ有機アミンとして原料アミンと共通の第一級アミンを使用しているのみである。また、低溶解性のマレアミド酸を原料としているため、特に原料の第一級アミンが複数のアミノ基を有している場合には、予めマレアミド酸を製造した後、ろ過による取出しあるいは大量の溶媒に溶解させる等の頻雑な操作が必要となる。
特許文献７記載の製造方法では、該文献の実施例記載の収率は高いが、本発明者が同様の操作で追試を行ったところ、マレアミド酸由来と思われる多量の不溶解分が副生し、記載されている結果を再現することはできなかった（本発明における比較例５参照）。 However, the methods for producing N-aliphatic substituted maleimide compounds described in Patent Documents 5 to 7 have the following problems.
The production method described in Patent Document 5 requires a high pressure and uses special reaction equipment, so it is difficult to say that it is a simple and general operation.
In Patent Document 6, the examples only use a phosphoric acid-based acid catalyst as the Bronsted acid and a primary amine common to the raw material amine as the organic amine. Moreover, since the low-solubility maleamic acid is used as a raw material, especially when the raw material primary amine has a plurality of amino groups, maleamic acid is produced in advance and then removed by filtration or a large amount of solvent. Therefore, it is necessary to perform a complicated operation such as dissolving it in the solution.
In the production method described in Patent Document 7, the yield described in the Examples of the document is high. However, when the present inventor made a follow-up test in the same manner, a large amount of insoluble matter that was thought to be derived from maleamic acid was produced as a by-product. However, the described results could not be reproduced (see Comparative Example 5 in the present invention).

すなわち、本発明は、穏和な条件下、簡便な操作で、目的とするＮ−脂肪族置換マレイミド化合物を副生物の生成を抑制して高選択的に効率よく得ることができる製造方法を提供することを課題とする。また、本発明は、目的とするＮ−脂肪族置換マレイミド化合物を好収率で得ることができる製造方法を提供することを課題とする。   That is, the present invention provides a production method capable of efficiently obtaining a desired N-aliphatic substituted maleimide compound with a high degree of selectivity under mild conditions by suppressing the production of by-products. This is the issue. Moreover, this invention makes it a subject to provide the manufacturing method which can obtain the target N-aliphatic substituted maleimide compound with a favorable yield.

本発明者は上記課題に鑑み、Ｎ−脂肪族置換マレイミド化合物の製造方法について鋭意研究を重ねた結果、Ｎ−脂肪族置換マレイミド化合物の合成反応における酸触媒と脱水助触媒に特定の組み合わせを採用し、さらに酸触媒に対する脱水助触媒の使用量を特定の範囲とすることで、目的物であるＮ−脂肪族置換マレイミド化合物を高選択的に高収率で得られることを見出した。すなわち本発明者は、上記酸触媒と脱水助触媒の存在下、脂肪族アミン化合物を供給することにより、前駆体のマレアミド酸及び触媒を析出させることなく、均一反応系で共沸脱水環化させることができ、マレアミド酸の異性化やポリイミド化の進行を抑制してイミド化の転化率を向上し得ること、これにより、目的のＮ−脂肪族置換マレイミド化合物を高選択的に、また効率を向上させて得ることできることを見出した。
本発明はこれらの知見に基づき完成されるに至ったものである。 In view of the above problems, the inventor has conducted extensive research on a method for producing an N-aliphatic substituted maleimide compound, and as a result, has adopted a specific combination for the acid catalyst and the dehydration promoter in the synthesis reaction of the N-aliphatic substituted maleimide compound. Furthermore, the inventors have found that the target N-aliphatic substituted maleimide compound can be obtained with high selectivity and high yield by setting the amount of the dehydration co-catalyst to the acid catalyst within a specific range. That is, the present inventor makes an azeotropic dehydration cyclization in a homogeneous reaction system without depositing the precursor maleamic acid and the catalyst by supplying an aliphatic amine compound in the presence of the acid catalyst and the dehydration cocatalyst. It is possible to improve the conversion rate of imidization by suppressing the progress of isomerization and polyimidation of maleamic acid. This makes it possible to select the target N-aliphatic substituted maleimide compound with high selectivity and efficiency. I found out that it can be improved.
The present invention has been completed based on these findings.

すなわち、上記の課題は以下の手段により解決された。
〔１〕
反応に使用する反応溶媒が水と共沸可能な有機溶媒のみから成り、
無水マレイン酸と、酸触媒と、脱水助触媒として該酸触媒に対し０．１５〜０．８モル当量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、下記一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給し、均一反応系で脱水環化させることを特徴とする、下記一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法。

（式中、Ｒはｎ価の脂肪族炭化水素基を示し、ｎは１〜６の整数である。）
〔２〕
前記脱水環化させた後の反応液を水で洗浄し、得られた水相を脱水した残留物を、前記の酸触媒および脱水助触媒またはそれらの一部として再利用することを特徴とする、〔１〕に記載の製造方法。
〔３〕
前記酸触媒が硫酸またはスルホン酸であることを特徴とする、〔１〕又は〔２〕に記載の製造方法。
〔４〕
前記酸触媒の使用量が、前記脂肪族第一級アミン化合物に対し１．０モル当量未満であることを特徴とする、〔１〕〜〔３〕のいずれか１つに記載の製造方法。
〔５〕
無水マレイン酸と、酸触媒と、脱水助触媒として該酸触媒に対し０．１５〜０．８モル当量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、下記一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給し、均一反応系で脱水環化させ、
前記酸触媒を前記脂肪族第一級アミン化合物１モルに対し、０．４〜１．０モル使用するせることを特徴とする、下記一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法。

（式中、Ｒはｎ価の脂肪族炭化水素基を示し、ｎは１〜６の整数である。）
〔６〕
前記第三級アミン化合物がトリアルキルアミンであることを特徴とする、〔１〕〜〔５〕のいずれか１つに記載の製造方法。 That is, the above problem has been solved by the following means.
[1]
The reaction solvent used for the reaction consists only of an organic solvent that can be azeotroped with water,
In a solution containing maleic anhydride, an acid catalyst, 0.15 to 0.8 molar equivalent of a tertiary amine compound with respect to the acid catalyst as a dehydration cocatalyst, and an organic solvent azeotropic with water, An aliphatic primary amine compound represented by the following general formula (1) or a solution thereof is supplied under reflux with heating, and dehydration cyclization is performed in a homogeneous reaction system, which is represented by the following general formula (2). Of producing an N-aliphatic substituted maleimide compound.

(In the formula, R represents an n-valent aliphatic hydrocarbon group, and n is an integer of 1 to 6.)
[2]
The reaction solution after the dehydration cyclization is washed with water, and the residue obtained by dehydrating the obtained aqueous phase is reused as the acid catalyst and the dehydration promoter or a part thereof. [1] The production method according to [1].
[3]
The production method according to [1] or [2], wherein the acid catalyst is sulfuric acid or sulfonic acid.
[4]
The production method according to any one of [1] to [3], wherein the amount of the acid catalyst used is less than 1.0 molar equivalent relative to the aliphatic primary amine compound.
[5]
In a solution containing maleic anhydride, an acid catalyst, 0.15 to 0.8 molar equivalent of a tertiary amine compound with respect to the acid catalyst as a dehydration cocatalyst, and an organic solvent azeotropic with water, Under heating and reflux, an aliphatic primary amine compound represented by the following general formula (1) or a solution thereof is supplied, and dehydration cyclization is performed in a homogeneous reaction system.
An N-aliphatic substituted maleimide represented by the following general formula (2), wherein the acid catalyst is used in an amount of 0.4 to 1.0 mol with respect to 1 mol of the aliphatic primary amine compound. Compound production method.

(In the formula, R represents an n-valent aliphatic hydrocarbon group, and n is an integer of 1 to 6.)
[6]
Characterized in that the tertiary amine compound is trialkylamine, producing how according to any one of [1] to [5].

本明細書において、組成、純度を表す「％」は、特段の断りのない限り質量基準である。
本明細書において、一般式（１）で表される脂肪族第一級アミン化合物に対するモル比は、「分子中のアミノ基の数×一般式（１）で表される脂肪族第一級アミン化合物のモル数」に対するモル比を意味する。 In this specification, “%” representing composition and purity is based on mass unless otherwise specified.
In the present specification, the molar ratio to the aliphatic primary amine compound represented by the general formula (1) is “the number of amino groups in the molecule × the aliphatic primary amine represented by the general formula (1)”. It means the molar ratio with respect to the “number of moles of compound”.

本発明のＮ−脂肪族置換マレイミド化合物の製造方法によれば、従来の方法と比較し、特殊な反応装置や、高価・高沸点の非プロトン性極性溶媒を用いることなく、穏和な条件下、簡便な操作で、目的とするＮ−脂肪族置換マレイミド化合物を高選択的に効率よく得ることができる。また、本発明のＮ−脂肪族置換マレイミド化合物の製造方法によれば、Ｎ−脂肪族置換マレイミド化合物を好収率で得ることができる。すなわち、本発明のＮ−脂肪族置換マレイミド化合物の製造方法は、Ｎ−脂肪族置換マレイミド化合物の工業的製造に好適である。
また、本発明のＮ−脂肪族置換マレイミド化合物の製造方法によれば、ジアミン化合物のような多置換性アミンを原料とした場合にも、対応する多置換性Ｎ−脂肪族置換マレイミド化合物を高選択的に製造することができる。 According to the method for producing an N-aliphatic substituted maleimide compound of the present invention, compared with the conventional method, without using a special reaction apparatus or an expensive, high-boiling aprotic polar solvent, The target N-aliphatic substituted maleimide compound can be efficiently obtained with high selectivity by a simple operation. Moreover, according to the manufacturing method of the N-aliphatic substituted maleimide compound of this invention, an N-aliphatic substituted maleimide compound can be obtained with a favorable yield. That is, the method for producing an N-aliphatic substituted maleimide compound of the present invention is suitable for industrial production of an N-aliphatic substituted maleimide compound.
In addition, according to the method for producing an N-aliphatic substituted maleimide compound of the present invention, even when a polysubstituted amine such as a diamine compound is used as a raw material, the corresponding polysubstituted N-aliphatic substituted maleimide compound is increased. It can be produced selectively.

本発明の好ましい実施形態について以下に説明する。
＜一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法＞
一般式（２）で表されるＮ−脂肪族置換マレイミド化合物は、無水マレイン酸と、酸触媒と、脱水助触媒として特定量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給し、均一反応系で脱水環化させることにより製造することができる。
ここで、「均一反応系で脱水環化させる」とは、触媒及び前駆体であるマレアミド酸等を析出させることなく、反応溶液中に溶解させた状態で脱水環化させることを意味する。すなわち、反応系が均一の液相で構成され、触媒及び前駆体であるマレアミド酸等が不溶解分（固相）として析出していない状態で、脱水環化させることを意味する。 Preferred embodiments of the present invention are described below.
<Method for producing N-aliphatic substituted maleimide compound represented by general formula (2)>
The N-aliphatic substituted maleimide compound represented by the general formula (2) includes maleic anhydride, an acid catalyst, a specific amount of a tertiary amine compound as a dehydration co-catalyst, an organic solvent azeotropic with water, Can be produced by supplying the aliphatic primary amine compound represented by the general formula (1) or a solution thereof under heating and refluxing and carrying out dehydration cyclization in a homogeneous reaction system.
Here, “dehydrating and cyclizing in a homogeneous reaction system” means dehydrating and cyclizing in a dissolved state in the reaction solution without precipitating the catalyst and the precursor maleamic acid or the like. That is, it means that the reaction system is composed of a uniform liquid phase, and dehydration cyclization is performed in a state where the catalyst and the precursor maleamic acid or the like are not precipitated as an insoluble component (solid phase).

−脂肪族第一級アミン化合物−
本発明における脱水環化反応では、下記一般式（１）で表される脂肪族第一級アミン化合物を用いる。 -Aliphatic primary amine compounds-
In the dehydration cyclization reaction in the present invention, an aliphatic primary amine compound represented by the following general formula (1) is used.

（式中、Ｒはｎ価の脂肪族炭化水素基を示し、ｎは１〜６の整数である。）   (In the formula, R represents an n-valent aliphatic hydrocarbon group, and n is an integer of 1 to 6.)

Ｒにおけるｎ価の脂肪族炭化水素基は、後述する置換基Ｚを有していてもよく、総炭素数は１〜３２が好ましく、１〜２０がより好ましく、１〜１６が好ましい。
ｎ価の脂肪族炭化水素基としては、直鎖状または分岐状であっても、環状構造を有していてもよい。以下、１価の脂肪族炭化水素基を代表として具体的な基を記載するが、２〜６価の脂肪族炭化水素基についても同様に、価数の異なる具体的な基を記載したものとする。
直鎖状又は分岐状の脂肪族炭化水素基としては、例えば、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、ｓｅｃ−ブチル基、イソブチル基、ｔ−ブチル基、ｎ−ペンチル基、ｎ−ヘキシル基等が挙げられる。
また、環状構造を有する脂肪族炭化水素基としては、例えば、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基等が挙げられる。
置換基Ｚとしては、例えば、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、ｓｅｃ−ブチル基、イソブチル基、ｔ−ブチル基、ｎ−ペンチル基、ｎ−ヘキシル基、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基等の炭素数１〜６のアルキル基；メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基等の、炭素数１〜６のアルコキシ基；例えば、フルオロメチル基、ジフルオロメチル基、トリフルオロメチル基等の炭素数１〜６のハロアルキル基；カルボキシル基又はその金属塩：（炭素数１〜６のカルボニル基；炭素数１〜６のアルキルアミノ基；炭素数１〜６のカルボニルアミノ基、；ニトロ基；ヒドロキシル基；フェニル基等のアリール基；フェノキシ基等のアリールオキシ基；ピリジル基、チエニル基、フラニル基等のヘテロアリール基が挙げられ、炭素数１〜６のアルキル基、炭素数１〜６のアルコキシ基、炭素数１〜６のハロアルキル基、炭素数１〜６のカルボニルアミノ基、；ニトロ基；ヒドロキシル基、アリール基、アリールオキシ基またはヘテロアリール基が好ましい。 The n-valent aliphatic hydrocarbon group in R may have a substituent Z described later, and the total carbon number is preferably 1 to 32, more preferably 1 to 20, and more preferably 1 to 16.
The n-valent aliphatic hydrocarbon group may be linear or branched or have a cyclic structure. Hereinafter, specific groups will be described with a monovalent aliphatic hydrocarbon group as a representative, but the specific groups having different valences are similarly described for the divalent to hexavalent aliphatic hydrocarbon groups. To do.
As the linear or branched aliphatic hydrocarbon group, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, t-butyl group, n -A pentyl group, n-hexyl group, etc. are mentioned.
Examples of the aliphatic hydrocarbon group having a cyclic structure include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
Examples of the substituent Z include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, t-butyl group, n-pentyl group, n-hexyl group, C1-C6 alkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; C1-C6 alkoxy group such as methoxy group, ethoxy group, n-propoxy group, isopropoxy group; , A haloalkyl group having 1 to 6 carbon atoms such as a fluoromethyl group, a difluoromethyl group and a trifluoromethyl group; a carboxyl group or a metal salt thereof: (a carbonyl group having 1 to 6 carbon atoms; an alkylamino group having 1 to 6 carbon atoms) A carbonylamino group having 1 to 6 carbon atoms; a nitro group; a hydroxyl group; an aryl group such as a phenyl group; an aryl group such as a phenoxy group; A heteroaryl group such as a pyridyl group, a thienyl group, and a furanyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, and 1 carbon atom A carbonylamino group of ˜6; a nitro group; a hydroxyl group, an aryl group, an aryloxy group or a heteroaryl group.

ｎは、１〜４が好ましく、１〜２がより好ましい。   n is preferably 1 to 4, and more preferably 1 to 2.

一般式（１）で表される脂肪族第一級アミン化合物としては、具体的には、メチルアミン、エチルアミン、ｎ−プロピルアミン、イソプロピルアミン、ｎ−ブチルアミン、ｓｅｃ−ブチルアミン、イソブチルアミン、ｔ−ブチルアミン、ｎ−ペンチルアミン、ｎ−ヘキシルアミン、エチレンジアミン、１、３−ジアミノプロパン、１、４−ジアミノブタン、１、６−ジアミノヘキサン、シクロプロピルアミン、シクロブチルアミン、シクロペンチルアミン、シクロヘキシルアミン、ベンジルアミン、２，２，４−トリメチルヘキサメチレンジアミン、２，４，４−トリメチルヘキサメチレンジアミン、イソホロンジアミン、４，４’−ビスアミノジシクロヘキシルメタン等を挙げることができる。   Specific examples of the aliphatic primary amine compound represented by the general formula (1) include methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, sec-butylamine, isobutylamine, t- Butylamine, n-pentylamine, n-hexylamine, ethylenediamine, 1,3-diaminopropane, 1,4-diaminobutane, 1,6-diaminohexane, cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, benzylamine 2,2,4-trimethylhexamethylenediamine, 2,4,4-trimethylhexamethylenediamine, isophoronediamine, 4,4′-bisaminodicyclohexylmethane, and the like.

−Ｎ−脂肪族置換マレイミド化合物−
本発明の製造方法により、下記一般式（２）で表されるＮ−脂肪族置換マレイミド化合物が得られる。 -N-aliphatic substituted maleimide compound-
By the production method of the present invention, an N-aliphatic substituted maleimide compound represented by the following general formula (2) is obtained.

（式中、Ｒ、ｎは上記一般式（１）のＲ及びｎと同義である。）

(In the formula, R and n have the same meanings as R and n in formula (1)).

一般式（２）で表されるＮ−脂肪族置換マレイミド化合物は、具体的には、Ｎ−メチルマレイミド、Ｎ−エチルマレイミド、Ｎ−（ｎ−プロピル）マレイミド、Ｎ−イソプロピルマレイミド、Ｎ−（ｎ−ブチル）マレイミド、Ｎ−（ｓｅｃ−ブチル）マレイミド、Ｎ−イソブチルマレイミド、Ｎ−（ｔ−ブチル）マレイミド、Ｎ−（ｎ−ペンチル）マレイミド、Ｎ−（ｎ−ヘキシル）マレイミド、１，２−ビス（マレイミド）エタン、１，３−ビス（マレイミド）プロパン、１，４−ビス（マレイミド）ブタン、１，５−ビス（マレイミド）ペンタン、１，６−ビス（マレイミド）ヘキサン、Ｎ−（シクロプロピルマレイミド、Ｎ−シクロブチルマレイミド、Ｎ−シクロペンチルマレイミド、Ｎ−シクロヘキシルマレイミド、Ｎ−ベンジルマレイミド、１，６−ビス（マレイミド）−２，２，４−トリメチルヘキサン、１，６−ビス（マレイミド）−２，４，４−トリメチルヘキサン、１−マレイミド−３−マレイミドメチル−３，５，５−トリメチルシクロヘキサン、４，４’−ビスマレイミドジシクロヘキシルメタン等を挙げることができる。   Specific examples of the N-aliphatic substituted maleimide compound represented by the general formula (2) include N-methylmaleimide, N-ethylmaleimide, N- (n-propyl) maleimide, N-isopropylmaleimide, N- ( n-butyl) maleimide, N- (sec-butyl) maleimide, N-isobutylmaleimide, N- (t-butyl) maleimide, N- (n-pentyl) maleimide, N- (n-hexyl) maleimide, 1,2 -Bis (maleimido) ethane, 1,3-bis (maleimido) propane, 1,4-bis (maleimido) butane, 1,5-bis (maleimido) pentane, 1,6-bis (maleimido) hexane, N- ( Cyclopropylmaleimide, N-cyclobutylmaleimide, N-cyclopentylmaleimide, N-cyclohexylmaleimide, N-benzylmer Imido, 1,6-bis (maleimide) -2,2,4-trimethylhexane, 1,6-bis (maleimide) -2,4,4-trimethylhexane, 1-maleimide-3-maleimidomethyl-3,5 , 5-trimethylcyclohexane, 4,4′-bismaleimide dicyclohexylmethane, and the like.

−酸触媒−
本発明の製造方法に用いる酸触媒としては、本発明における反応（以下、当反応と称す。）が可能な酸触媒であればいずれでも構わない。具体的には、メタンスルホン酸等の脂肪族スルホン酸、ならびに、ｐ−トルエンスルホン酸、ベンゼンスルホン酸およびキシレンスルホン酸等の芳香族スルホン酸を包含するスルホン酸；硫酸、発煙硫酸、リン酸等の鉱酸；ギ酸、酢酸、トリフルオロ酢酸等のカルボン酸；三フッ化ホウ素−テトラヒドロフラン（ＴＨＦ）錯体、塩化アルミニウム、塩化亜鉛等のルイス酸；モンモリロナイトＫ−１０、硫酸化ジルコニア等の固体酸等を挙げることができる。
上記酸触媒としては、入手性、取り扱いの簡便さ、溶解性、反応性等の観点から、ｐ−トルエンスルホン酸等のスルホン酸、ならびに、硫酸および発煙硫酸等の鉱酸が好ましい。なかでも、後述する水と共沸可能な有機溶媒としてトルエン、キシレン等の芳香族炭化水素を用いる場合には、加熱脱水によりスルホン化することができ、より均一反応系となりやすい点から、硫酸がより好ましい。
これらの酸触媒は単独で用いても、任意の割合で２種類以上を用いてもよい。 -Acid catalyst-
The acid catalyst used in the production method of the present invention may be any acid catalyst as long as it is capable of performing the reaction in the present invention (hereinafter referred to as this reaction). Specifically, sulfonic acids including aliphatic sulfonic acids such as methanesulfonic acid, and aromatic sulfonic acids such as p-toluenesulfonic acid, benzenesulfonic acid and xylenesulfonic acid; sulfuric acid, fuming sulfuric acid, phosphoric acid and the like Mineral acids; carboxylic acids such as formic acid, acetic acid and trifluoroacetic acid; Lewis acids such as boron trifluoride-tetrahydrofuran (THF) complex, aluminum chloride and zinc chloride; solid acids such as montmorillonite K-10 and sulfated zirconia Can be mentioned.
As the acid catalyst, sulfonic acids such as p-toluenesulfonic acid and mineral acids such as sulfuric acid and fuming sulfuric acid are preferable from the viewpoint of availability, ease of handling, solubility, and reactivity. In particular, when an aromatic hydrocarbon such as toluene or xylene is used as an organic solvent that can be azeotroped with water, which will be described later, sulfuric acid can be sulfonated by heating and dehydration, and a more uniform reaction system can be obtained. More preferred.
These acid catalysts may be used alone or in combination of two or more at any ratio.

上記酸触媒の使用量は、特に制限するものではないが、一般式（１）で表される脂肪族第一級アミン化合物１モルに対して、通常は０．０１〜１．０モルであり、好ましくは０．１〜０．９モル、より好ましくは０．２〜０．８モルの範囲である。
酸触媒が少なすぎると、イミド化の反応速度が低下し、前駆体であるマレアミド酸の異性化あるいはポリイミド化が進行することによりイミド化の転化率が低下し、収率が低下する傾向がある。また、経済的な観点からは、酸触媒は多すぎないことが好ましい。 Although the usage-amount of the said acid catalyst is not restrict | limited in particular, It is 0.01-1.0 mol normally with respect to 1 mol of aliphatic primary amine compounds represented by General formula (1). The range is preferably 0.1 to 0.9 mol, more preferably 0.2 to 0.8 mol.
If the amount of the acid catalyst is too small, the reaction rate of imidization decreases, and the conversion of imidization tends to decrease and the yield tends to decrease due to the progress of isomerization or polyimidation of the precursor maleamic acid. . Also, from an economical viewpoint, it is preferable that there are not too many acid catalysts.

−脱水助触媒（第三級アミン化合物）−
本発明の製造方法に用いる第三級アミン化合物としては、当反応が可能な第三級アミン化合物であればいずれでも構わない。ここで、第三級アミン化合物とは、アンモニアの水素原子が３つとも炭素原子で置換された化合物を意味する。具体的には例えば、トリメチルアミン、トリエチルアミン、トリブチルアミン、Ｎ−メチルモルホリン等のトリアルキルアミン（総炭素数３〜１５が好ましく、３〜１２がより好ましい。）；ジメチルアニリン、ジフェニルメチルアミン、トリフェニルアミン等の第三級芳香族アミン（総炭素数８〜２０が好ましく、８〜１５がより好ましい。）；ピリジン、キノリン、ピロール、ピラゾール、トリアゾール等の含窒素ヘテロ環芳香族化合物を挙げることができる。
上記第三級アミン化合物としては、入手性や取り扱いの簡便さ、溶解性、反応性、水溶性等の観点から、トリメチルアミン、トリエチルアミン、トリブチルアミン、Ｎ−メチルモルホリン等のトリアルキルアミンが好ましい。
これらの第三級アミン化合物は単独で用いても、任意の割合で２種類以上を用いてもよい。 -Dehydration cocatalyst (tertiary amine compound)-
The tertiary amine compound used in the production method of the present invention may be any tertiary amine compound capable of this reaction. Here, the tertiary amine compound means a compound in which all three hydrogen atoms of ammonia are substituted with carbon atoms. Specifically, for example, trialkylamines such as trimethylamine, triethylamine, tributylamine, N-methylmorpholine (total carbon number is preferably 3-15, more preferably 3-12); dimethylaniline, diphenylmethylamine, triphenyl Tertiary aromatic amines such as amines (preferably having a total carbon number of 8 to 20 and more preferably 8 to 15); and nitrogen-containing heterocyclic aromatic compounds such as pyridine, quinoline, pyrrole, pyrazole and triazole. it can.
The tertiary amine compound is preferably a trialkylamine such as trimethylamine, triethylamine, tributylamine or N-methylmorpholine from the viewpoints of availability, ease of handling, solubility, reactivity, water solubility and the like.
These tertiary amine compounds may be used alone or in combination of two or more at any ratio.

上記第三級アミン化合物の使用量は、上記酸触媒に対して１モル当量未満であれば当反応は進行するが、本発明においては、酸触媒に対して、０．１５〜０．８モル当量であり、好ましくは０．２〜０．７モル当量、より好ましくは０．３〜０．６モル当量である。
第三級アミン化合物が少なすぎると、イミド化の反応速度が低下し、前駆体であるマレアミド酸の異性化あるいはポリイミド化が進行することによりイミド化の転化率が低下し、収率が低下する傾向がある（比較例１参照）。また、経済的および反応性の観点からは、第三級アミン化合物は多すぎないことが好ましい（比較例４参照）。 The reaction proceeds if the amount of the tertiary amine compound used is less than 1 molar equivalent relative to the acid catalyst, but in the present invention, 0.15 to 0.8 mol relative to the acid catalyst. Equivalent, preferably 0.2 to 0.7 molar equivalent, more preferably 0.3 to 0.6 molar equivalent.
If the amount of the tertiary amine compound is too small, the reaction rate of imidization decreases, and the conversion of imidization decreases due to the progress of isomerization or polyimidation of the maleamic acid precursor, resulting in a decrease in yield. There is a tendency (see Comparative Example 1). Moreover, it is preferable that there are not too many tertiary amine compounds from economical and reactive viewpoints (refer to Comparative Example 4).

−無水マレイン酸−
本発明の製造方法における無水マレイン酸の使用量は、特に制限するものではないが、一般式（１）で表される脂肪族第一級アミン化合物１モルに対して、通常０．５〜５．０モルであり、好ましくは０．８〜２．０モル、より好ましくは１．０〜１．５モルである。
反応を完結させたい場合には、前駆体であるマレアミド酸が無水マレイン酸との反応により混合酸無水物となることでイミド化が促進されると考えられるため、一般式（１）で表される脂肪族第一級アミン化合物に対し小過剰の無水マレイン酸（具体的には、１．０５モル以上が好ましく、１．１モル以上がより好ましい。）を用いることが好ましい。また、一般式（１）で表される脂肪族第一級アミン化合物が一般式（２）で表されるＮ−脂肪族置換マレイミド化合物にマイケル付加した副生成物が生成することによる収率の低下を抑制する点からも、一般式（１）で表される脂肪族第一級アミン化合物に対し小過剰の無水マレイン酸を用いることが好ましい。 -Maleic anhydride-
The amount of maleic anhydride used in the production method of the present invention is not particularly limited, but is usually 0.5 to 5 with respect to 1 mol of the aliphatic primary amine compound represented by the general formula (1). 0.0 mol, preferably 0.8 to 2.0 mol, more preferably 1.0 to 1.5 mol.
When it is desired to complete the reaction, it is considered that imidization is promoted by the maleamic acid, which is a precursor, becoming a mixed acid anhydride by reaction with maleic anhydride, and therefore, represented by the general formula (1). It is preferable to use a small excess of maleic anhydride (specifically, 1.05 mol or more is preferable, and 1.1 mol or more is more preferable) with respect to the aliphatic primary amine compound. Moreover, the yield by the by-product which the aliphatic primary amine compound represented by General formula (1) added Michael to the N-aliphatic substituted maleimide compound represented by General formula (2) produces | generates. From the viewpoint of suppressing the decrease, it is preferable to use a small excess of maleic anhydride relative to the aliphatic primary amine compound represented by the general formula (1).

−重合禁止剤−
本発明の製造方法においては、目的物であるＮ−脂肪族置換マレイミド化合物が反応液中で重合する可能性がある場合に、重合禁止剤を用いても良い。当反応に用いる重合禁止剤としては、例えば、ヒンダードフェノール類及び銅化合物等の重合禁止剤が挙げられる。 -Polymerization inhibitor-
In the production method of the present invention, a polymerization inhibitor may be used when the target N-aliphatic substituted maleimide compound may be polymerized in the reaction solution. Examples of the polymerization inhibitor used in this reaction include polymerization inhibitors such as hindered phenols and copper compounds.

ヒンダードフェノール類としては、４−メトキシフェノール、２，６−ジ−ｔ−ブチル−ｐ−クレゾール、２，５−ジ−ｔ−アミルヒドロキノン、４，４’−ブチリデンビス（６−ｔ−ブチル−３−メチル−フェノール）、２，２’−メチレンビス（４−メチル−６−ｔ−ブチルフェノール）、２，２’−メチレンビス（４−エチル−６−ｔ−ブチルフェノール）等が挙げられる。
銅化合物としては、有機及び無機のいずれの銅化合物でもよく、金属銅、酸化銅、水酸化銅、塩化銅、硫酸銅、酢酸銅、ジブチルジチオカルバミン酸銅、ジメチルジチオカルバミン酸銅等が挙げられる。
上記重合禁止剤は、単独で添加しても、混合物として添加してもよい。 Examples of hindered phenols include 4-methoxyphenol, 2,6-di-t-butyl-p-cresol, 2,5-di-t-amylhydroquinone, 4,4′-butylidenebis (6-t-butyl- 3-methyl-phenol), 2,2′-methylenebis (4-methyl-6-tert-butylphenol), 2,2′-methylenebis (4-ethyl-6-tert-butylphenol) and the like.
The copper compound may be any organic or inorganic copper compound, and examples thereof include metal copper, copper oxide, copper hydroxide, copper chloride, copper sulfate, copper acetate, copper dibutyldithiocarbamate, and copper dimethyldithiocarbamate.
The polymerization inhibitor may be added alone or as a mixture.

本発明の製造方法において、重合禁止剤の使用量は、特に制限するものではないが、一般式（１）で表される脂肪族第一級アミン化合物１モルに対して、通常０．００００１〜１．０モルであり、好ましくは０．００００５〜０．１モル、より好ましくは０．０００１〜０．０１モルである。   In the production method of the present invention, the amount of the polymerization inhibitor used is not particularly limited, but is usually from 0.00001 to 1 per 1 mol of the aliphatic primary amine compound represented by the general formula (1). 1.0 mol, preferably 0.00005 to 0.1 mol, more preferably 0.0001 to 0.01 mol.

−溶媒−
当反応は無溶媒で実施してもよいが、反応を円滑に進行するため、本発明においては、反応を阻害せず、水に不溶かつ水と共沸可能な溶媒（単に「水と共沸可能な溶媒」とも称す。）を用いる。
水と共沸可能な溶媒は、例えば、トルエン、キシレン等の芳香族炭化水素溶媒；クロロベンゼン、ジクロロメタン等の含ハロゲン溶媒；ｎ−ヘキサン、シクロヘキサン、ｎ−デカン等の脂肪族炭化水素溶媒が挙げられる。反応系がより均一反応系となりやすい点から、トルエン、キシレン等の芳香族炭化水素溶媒が好ましい。無水マレイン酸と酸触媒と脱水助触媒である第三級アミン化合物と共に溶液を構成する水と共沸可能な溶媒と、第一級アミン化合物の溶液を構成する溶媒とは、同一であることが好ましい。 -Solvent-
Although this reaction may be carried out without a solvent, in order that the reaction proceeds smoothly, in the present invention, a solvent that does not inhibit the reaction and is insoluble in water and azeotropic with water (simply referred to as “azeotrope with water”). Also referred to as “possible solvent”.
Examples of the azeotropic solvent with water include aromatic hydrocarbon solvents such as toluene and xylene; halogen-containing solvents such as chlorobenzene and dichloromethane; and aliphatic hydrocarbon solvents such as n-hexane, cyclohexane and n-decane. . Aromatic hydrocarbon solvents such as toluene and xylene are preferred because the reaction system tends to become a more homogeneous reaction system. The solvent that can form an azeotrope with water that forms the solution together with the maleic anhydride, the acid catalyst, and the tertiary amine compound that serves as the dehydration cocatalyst, and the solvent that forms the solution of the primary amine compound must be the same. preferable.

溶媒は単独で使用しても、任意の混合割合の混合溶媒として使用してもよい。   A solvent may be used independently or may be used as a mixed solvent of arbitrary mixing ratios.

溶媒量としては、反応系の攪拌が充分にできる量であれば良いが、一般式（１）で表される脂肪族第一級アミン化合物１モルに対して、通常０〜１０Ｌであり、好ましくは０．２〜２Ｌである。   The amount of the solvent may be an amount that can sufficiently stir the reaction system, but is usually 0 to 10 L with respect to 1 mol of the aliphatic primary amine compound represented by the general formula (1), preferably Is 0.2-2L.

−反応工程−
当反応は、まず、酸触媒存在下で水と共沸可能な有機溶媒を還流し、酸触媒に含まれる水分あるいはスルホン化等により生成する水を共沸により留去する。その後、反応系を冷却してから第三級アミン化合物、無水マレイン酸、用いるならば重合禁止剤を順次加える。これらの溶液を再度加熱還流しているところへ、均一反応系にて一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を徐々に供給する。無水マレイン酸と反応して生成するマレアミド酸を、生成する水を順次共沸により除去しつつ脱水環化反応を進行させ、一般式（２）で表されるＮ−脂肪族置換マレイミド化合物を得る。
一般式（１）で表される脂肪族第一級アミン化合物と無水マレイン酸とを予め反応させた後、生成するマレアミド酸を添加する方法は、反応性の低下を招き、一般式（２）で表されるＮ−脂肪族置換マレイミド化合物を収率よく得られない（比較例３参照）。 -Reaction process-
In this reaction, first, an organic solvent which can be azeotroped with water is refluxed in the presence of an acid catalyst, and water contained in the acid catalyst or water produced by sulfonation is distilled off by azeotropic distillation. Then, after cooling the reaction system, a tertiary amine compound, maleic anhydride and, if used, a polymerization inhibitor are sequentially added. The aliphatic primary amine compound represented by the general formula (1) or a solution thereof is gradually supplied to the place where these solutions are heated and refluxed again in a homogeneous reaction system. The maleamic acid produced by the reaction with maleic anhydride is subjected to a dehydration cyclization reaction while sequentially removing the produced water by azeotropic distillation to obtain an N-aliphatic substituted maleimide compound represented by the general formula (2). .
The method of reacting the aliphatic primary amine compound represented by the general formula (1) with maleic anhydride in advance and then adding the resulting maleamic acid causes a decrease in reactivity, and the general formula (2) The N-aliphatic substituted maleimide compound represented by the above formula cannot be obtained in good yield (see Comparative Example 3).

一般式（１）で表される脂肪族第一級アミン化合物またはその溶液の供給時の反応温度は、８０℃〜使用する溶媒の還流温度という範囲を例示できるが、反応性向上の観点から、１００〜１６０℃の範囲が好ましい。反応速度や反応設備の都合上、溶媒の還流温度を調整するために加圧もしくは減圧条件下で反応を実施してもよい。
本発明では脂肪族第一級アミン化合物もしくはその溶液の供給時の無水マレイン酸等の溶液の温度を溶媒の還流温度と記載する。この「溶媒の還流温度」とは、上記のように脱水環化反応を進行させるために反応生成水を除去しながら溶媒の一部が還流する温度を意味し、溶媒及び反応生成水を全還流させるという意味はない。 Although the reaction temperature at the time of supply of the aliphatic primary amine compound represented by the general formula (1) or a solution thereof can range from 80 ° C. to the reflux temperature of the solvent used, from the viewpoint of improving the reactivity, The range of 100-160 degreeC is preferable. For the convenience of reaction rate and reaction equipment, the reaction may be carried out under pressure or reduced pressure to adjust the reflux temperature of the solvent.
In the present invention, the temperature of a solution such as maleic anhydride when the aliphatic primary amine compound or its solution is supplied is referred to as the reflux temperature of the solvent. The “solvent reflux temperature” means a temperature at which a part of the solvent is refluxed while removing the reaction product water to advance the dehydration cyclization reaction as described above. The solvent and the reaction product water are totally refluxed. There is no meaning of letting it.

一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給する方法としては、落差又はポンプを用いる滴下が一般的であるが、供給速度、すなわち滴下速度を調整できれば特に問わない。
滴下時の滴下時間は、均一反応系で脱水環化される限り、酸触媒および第三級アミン化合物の使用モル比に応じて適宜調整される。なかでも、一般式（１）で表される脂肪族第一級アミン化合物と無水マレイン酸が反応して生成するマレアミド酸の異性化やポリイミド化などの副反応が充分抑制され、イミド化閉環反応が優先的に進行する速度を保つ観点等から、好ましくは１時間〜３０時間である。 As a method of supplying the aliphatic primary amine compound represented by the general formula (1) or a solution thereof, drop or dropping using a pump is generally used, but it is particularly important if the supply rate, that is, the dropping rate can be adjusted. Absent.
The dropping time at the time of dropping is appropriately adjusted according to the molar ratio of the acid catalyst and the tertiary amine compound as long as the cyclodehydration is carried out in a homogeneous reaction system. In particular, side reactions such as isomerization and polyimidation of maleamic acid produced by the reaction of the aliphatic primary amine compound represented by the general formula (1) with maleic anhydride are sufficiently suppressed, and imidization ring closure reaction. From the standpoint of maintaining the speed at which preferentially proceeds, it is preferably 1 hour to 30 hours.

当反応により得られる一般式（２）で表されるＮ−脂肪族置換マレイミド化合物を含む反応液（すなわち、脱水環化反応終了後の反応液）は、水または塩基性水溶液で洗浄する。
塩基性水溶液としては、例えば、アルカリ金属あるいはアルカリ土類金属の水酸化物、炭酸塩もしくは炭酸水素塩の水溶液が使用できる。一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の塩基に対する安定性から、アルカリ金属あるいはアルカリ土類金属の炭酸水素塩の水溶液が好ましい。
水または塩基性水溶液の使用量としては、洗浄後に有機相と水相が分離する量であれば特に制限はないが、一般式（１）で表される脂肪族第一級アミン化合物１モルに対して、通常０．０１〜１０Ｌであり、好ましくは０．０５〜１Ｌである。 The reaction solution containing the N-aliphatic substituted maleimide compound represented by the general formula (2) obtained by this reaction (that is, the reaction solution after completion of the dehydration cyclization reaction) is washed with water or a basic aqueous solution.
As the basic aqueous solution, for example, an alkali metal or alkaline earth metal hydroxide, carbonate or hydrogen carbonate aqueous solution can be used. In view of the stability of the N-aliphatic substituted maleimide compound represented by the general formula (2) with respect to the base, an aqueous solution of an alkali metal or alkaline earth metal bicarbonate is preferable.
The amount of water or basic aqueous solution used is not particularly limited as long as the organic phase and the aqueous phase are separated after washing, but 1 mol of the aliphatic primary amine compound represented by the general formula (1) is used. On the other hand, it is 0.01-10L normally, Preferably it is 0.05-1L.

また、水で洗浄した場合、回収した水相を脱水して得られる残留物を、酸触媒および脱水助触媒またはそれらの一部として再利用してもよい。上記残留物には、酸触媒および脱水助触媒の他に、重合禁止剤等の成分が含まれ得る。   In the case of washing with water, the residue obtained by dehydrating the recovered aqueous phase may be reused as an acid catalyst and a dehydration promoter or a part thereof. The residue may contain components such as a polymerization inhibitor in addition to the acid catalyst and the dehydration promoter.

洗浄の温度は洗浄後に有機相と水相が分離する温度であれば特に制限はないが、通常０〜９０℃であり、好ましくは室温（２０℃）〜８０℃である。   The washing temperature is not particularly limited as long as it is a temperature at which the organic phase and the aqueous phase are separated after washing, but is usually 0 to 90 ° C, preferably room temperature (20 ° C) to 80 ° C.

本発明の製造方法により得られる、一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の単離方法に、特に制限はなく、常法により行うことができる。
例えば、洗浄後の有機相から溶媒を留去した後、蒸留するか、貧溶媒を加えて結晶を析出させた後にろ過することにより、一般式（２）で表されるＮ−脂肪族置換マレイミド化合物を単離することができる。 There is no restriction | limiting in particular in the isolation method of the N-aliphatic substituted maleimide compound represented by General formula (2) obtained by the manufacturing method of this invention, It can carry out by a conventional method.
For example, the N-aliphatic substituted maleimide represented by the general formula (2) is obtained by distilling off the solvent from the washed organic phase, followed by distillation or adding a poor solvent to precipitate crystals, followed by filtration. The compound can be isolated.

本発明の製造方法により得られる一般式（２）で表されるＮ−脂肪族置換マレイミド化合物は、樹脂モノマー、医農薬中間体として有用な化合物である。   The N-aliphatic substituted maleimide compound represented by the general formula (2) obtained by the production method of the present invention is a useful compound as a resin monomer and an intermediate for medicines and agricultural chemicals.

次に、実施例を挙げて本発明化合物の製造方法を具体的に説明するが、本発明は、これら実施例によって何ら限定されるものではない。
ここで、「洗浄後の反応液中の目的物の収率」は、ＨＰＬＣ（高速液体クロマトグラフィー）による内部標準法により算出した。 Next, although the Example is given and the manufacturing method of this invention compound is demonstrated concretely, this invention is not limited at all by these Examples.
Here, the “yield of the target product in the reaction solution after washing” was calculated by an internal standard method using HPLC (high performance liquid chromatography).

［１．Ｎ−シクロヘキシルマレイミドの製造］
以下、実施例１〜４、比較例１〜５の製造方法により、それぞれＮ−シクロヘキシルマレイミドを製造した。 [1. Production of N-cyclohexylmaleimide]
Hereinafter, N-cyclohexylmaleimide was produced by the production methods of Examples 1 to 4 and Comparative Examples 1 to 5, respectively.

実施例１
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた１０００ｍｌ容の四つ口フラスコに、濃硫酸３９．２ｇ（０．４ｍｏｌ）、キシレン２００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約７．２ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン２０．２ｇ（０．２ｍｏｌ）をキシレン７０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸１１０．０ｇ（１．１ｍｏｌ）、ジブチルジチオカルバミン酸銅７２ｍｇ（０．１６ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながらシクロヘキシルアミン１００．０ｇ（１ｍｏｌ）をキシレン１２０ｍｌに加えた溶液を、共沸する水を抜き出しつつ８時間掛けて滴下した。滴下後さらに３時間還流し、約１７．８ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで洗浄した。得られた水相は実施例２にて触媒リサイクルで使用した。さらに、反応液を２％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。洗浄後の反応液中には、収率８８．５％に相当するＮ−シクロヘキシルマレイミドが生成していた。さらに反応液にジブチルジチオカルバミン酸銅０．４ｇ（０．８５ｍｍｏｌ）を加え、減圧下キシレンを留去した後、１ｍｍＨｇの減圧下、バス温を１１５〜１５０℃まで昇温し蒸留を行い、Ｎ−シクロヘキシルマレイミドが１５２．６ｇの白色結晶として得られた。ＨＰＬＣ純度９９．９％、収率８５．２％。 Example 1
To a 1000 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer, 39.2 g (0.4 mol) of concentrated sulfuric acid and 200 ml of xylene are added, and nitrogen is allowed to flow into the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 7.2 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 20.2 g (0.2 mol) of triethylamine to 70 ml of xylene was adjusted so that the temperature in the reaction system was 100 ° C. or less. It was dripped. To the reaction system, 110.0 g (1.1 mol) of maleic anhydride, 72 mg (0.16 mmol) of copper dibutyldithiocarbamate and 10 ml of xylene were sequentially added. Next, a solution obtained by adding 100.0 g (1 mol) of cyclohexylamine to 120 ml of xylene was added dropwise over 8 hours while extracting azeotropic water while refluxing the reaction solution. After the dropwise addition, the mixture was further refluxed for 3 hours to separate about 17.8 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 200 ml of water. The obtained aqueous phase was used for catalyst recycling in Example 2. Further, the reaction solution was washed twice with 200 ml of 2% aqueous sodium bicarbonate solution and then with 200 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 88.5% was formed. Further, 0.4 g (0.85 mmol) of copper dibutyldithiocarbamate was added to the reaction solution, and xylene was distilled off under reduced pressure. After distillation under reduced pressure of 1 mmHg, the bath temperature was raised to 115 to 150 ° C. to perform distillation. Cyclohexylmaleimide was obtained as 152.6 g of white crystals. HPLC purity 99.9%, yield 85.2%.

ＧＣ−ＭＳ（Ｍ＋）^＋＝１７９．１． GC-MS (M +) ⁺ = 179.1.

実施例２
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、実施例１で得られた１回目の洗浄水８１．４ｇ（洗浄水の総量の１／４に相当、濃硫酸８．８ｇ（９０ｍｍｏｌ）、トリエチルアミン５.０ｇ（４９ｍｍｏｌ）含有）を加え、３０ｍｍＨｇの減圧下、バス温を１００℃まで昇温し水を留去した。次いで、ｐ−トルエンスルホン酸一水和物１．９ｇ（１０ｍｍｏｌ）およびキシレン１００ｍｌを加え反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。副生水の完全な留出を確認後、反応液を７０℃まで冷却後、反応系内に無水マレイン酸３０ｇ（０．３ｍｏｌ）を加えた。次いで反応液を還流させながらシクロヘキシルアミン２５ｇ（０．２５ｍｏｌ）をキシレン５０ｍｌに加えた溶液を、共沸する水を抜き出しつつ７時間掛けて滴下した。滴下後さらに２時間還流し、約４．８ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水５０ｍｌで洗浄した。さらに、反応液を２％重曹水溶液５０ｍｌ、次いで水５０ｍｌで２回洗浄した。洗浄後の反応液中には、収率９８．５％に相当するＮ−シクロヘキシルマレイミドが生成していた。さらに反応液にジブチルジチオカルバミン酸銅０．１ｇ（０．２１ｍｍｏｌ）を加え、減圧下キシレンを留去した後、１ｍｍＨｇの減圧下、バス温を１１０〜１４０℃まで昇温し蒸留を行い、Ｎ−シクロヘキシルマレイミドが３８．１ｇの白色結晶として得られた。ＨＰＬＣ純度９９．６％、収率８５．１％。 Example 2
In a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, and thermometer, 81.4 g of the first washing water obtained in Example 1 (1 / of the total amount of washing water) was obtained. 4), concentrated sulfuric acid (8.8 g, 90 mmol) and triethylamine (5.0 g, 49 mmol) were added, and the bath temperature was raised to 100 ° C. under a reduced pressure of 30 mmHg, and water was distilled off. Subsequently, 1.9 g (10 mmol) of p-toluenesulfonic acid monohydrate and 100 ml of xylene were added and refluxed while extracting azeotropic water while flowing nitrogen into the reaction system. After confirming complete distillation of the by-product water, the reaction solution was cooled to 70 ° C., and 30 g (0.3 mol) of maleic anhydride was added to the reaction system. Next, a solution obtained by adding 25 g (0.25 mol) of cyclohexylamine to 50 ml of xylene was added dropwise over 7 hours while extracting azeotropic water while refluxing the reaction solution. After the addition, the mixture was further refluxed for 2 hours to separate about 4.8 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 50 ml of water. Further, the reaction solution was washed twice with 50 ml of 2% aqueous sodium bicarbonate solution and then with 50 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 98.5% was formed. Further, 0.1 g (0.21 mmol) of copper dibutyldithiocarbamate was added to the reaction solution, and xylene was distilled off under reduced pressure. After distillation under reduced pressure of 1 mmHg, the bath temperature was raised to 110-140 ° C. to perform distillation. Cyclohexylmaleimide was obtained as 38.1 g of white crystals. HPLC purity 99.6%, yield 85.1%.

すなわち、この操作により含触媒水相の一部リサイクルが可能であった。   That is, this operation enabled partial recycling of the catalyst-containing aqueous phase.

実施例３
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸９．８ｇ（０．１ｍｏｌ）、キシレン５０ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約１．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリブチルアミン９．３ｇ（５０ｍｍｏｌ）をキシレン５０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸２５．０ｇ（２５０ｍｍｏｌ）、４−メトキシフェノール６０ｍｇ（０．５ｍｍｏｌ）を順次加えた。次いで反応液を還流させながらシクロヘキシルアミン２５．０ｇ（２５０ｍｍｏｌ）をキシレン５０ｍｌに加えた溶液を、共沸する水を抜き出しつつ６時間掛けて滴下した。滴下後さらに３時間還流し、約４．８ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで４回洗浄した。洗浄後の反応液中には、収率８７．３％に相当するＮ−シクロヘキシルマレイミドが生成していた。 Example 3
Concentrated sulfuric acid (9.8 g, 0.1 mol) and xylene (50 ml) were added to a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, and thermometer, and nitrogen was allowed to flow through the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 1.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 9.3 g (50 mmol) of tributylamine to 50 ml of xylene was added dropwise so that the temperature in the reaction system was 100 ° C. or less. did. Maleic anhydride 25.0 g (250 mmol) and 4-methoxyphenol 60 mg (0.5 mmol) were sequentially added to the reaction system. Next, a solution obtained by adding 25.0 g (250 mmol) of cyclohexylamine to 50 ml of xylene was added dropwise over 6 hours while extracting azeotropic water while refluxing the reaction solution. After the dropwise addition, the mixture was further refluxed for 3 hours to separate about 4.8 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed 4 times with 200 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 87.3% was formed.

実施例４
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた５００ｍｌ容の四つ口フラスコに、濃硫酸２９．４ｇ（０．３ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約５．６ｍｌの副生水を確認後、反応液を７０℃まで冷却後、ジメチルアニリン１２．１ｇ（０．１ｍｏｌ）をキシレン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながらシクロヘキシルアミン５０．０ｇ（０．５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ４時間掛けて滴下した。滴下後さらに２時間還流し、約８．６ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで洗浄した。さらに、反応液を２．５％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。洗浄後の反応液中には、収率８１．１％に相当するＮ−シクロヘキシルマレイミドが生成していた。 Example 4
Concentrated sulfuric acid (29.4 g, 0.3 mol) and xylene (100 ml) were added to a 500 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, and thermometer, and nitrogen was allowed to flow through the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 5.6 ml of by-product water, the reaction solution is cooled to 70 ° C., and then a solution obtained by adding 12.1 g (0.1 mol) of dimethylaniline to 20 ml of xylene is set so that the temperature in the reaction system becomes 100 ° C. or less. It was dripped in. Maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and xylene 10 ml were sequentially added to the reaction system. Next, a solution obtained by adding 50.0 g (0.5 mol) of cyclohexylamine to 70 ml of xylene was added dropwise over 4 hours while extracting azeotropic water while refluxing the reaction solution. After the addition, the mixture was further refluxed for 2 hours to separate about 8.6 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of a 2.5% aqueous sodium bicarbonate solution and then with 200 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 81.1% was formed.

比較例１
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた５００ｍｌ容の四つ口フラスコに、濃硫酸２９．４ｇ（３００ｍｍｏｌ）、キシレン１２０ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約５．６ｍｌの副生水を確認後、反応液を７０℃まで冷却後、無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを添加し、次いで反応液を還流させながらシクロヘキシルアミン５０．０ｇ（０．５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ４時間掛けて滴下した。滴下後さらに２時間還流し、約９．０ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで洗浄し、反応液を２％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。洗浄後の反応液中には、収率６７．１％に相当するＮ−シクロヘキシルマレイミドが生成していた。 Comparative Example 1
To a 500 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer, 29.4 g (300 mmol) of concentrated sulfuric acid and 120 ml of xylene were added, and while flowing nitrogen into the reaction system, The mixture was refluxed while removing azeotropic water. After confirming about 5.6 ml of by-product water, the reaction solution was cooled to 70 ° C., 55.0 g (550 mmol) of maleic anhydride, 36 mg (0.08 mmol) of copper dibutyldithiocarbamate, and 10 ml of xylene were added, followed by reaction. While the liquid was refluxed, a solution in which 50.0 g (0.5 mol) of cyclohexylamine was added to 70 ml of xylene was dropped over 4 hours while extracting azeotropic water. After the dropwise addition, the mixture was further refluxed for 2 hours to separate about 9.0 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 200 ml of water, and the reaction solution was washed twice with 200 ml of 2% aqueous sodium bicarbonate solution and then with 200 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 67.1% was formed.

比較例２
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸１４．７ｇ（１５０ｍｍｏｌ）、ｏ−キシレン５０ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約２．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、４−メトキシフェノール９０ｍｇ（０．７５ｍｍｏｌ）、シクロヘキシルアミン７．５ｇ（７５ｍｍｏｌ）を添加し、次いで反応液を還流させながらシクロヘキシルアミン２５．０ｇ（２５０ｍｍｏｌ）をｏ−キシレン５０ｍｌに加えた溶液と、無水マレイン酸２５．０ｇ（２５０ｍｍｏｌ）をｏ−キシレン５０ｍｌに加えた溶液を、共沸する水を抜き出しつつ２．５時間掛けて同時滴下した。滴下後さらに２時間還流し、約２．７ｍｌの副生水を分離した。１０℃以下まで反応液を冷却後、析出した結晶をろ過で除去し、反応液を水１００ｍｌで５回洗浄した。洗浄後の反応液中には、収率６４．０％に相当するＮ−シクロヘキシルマレイミドが生成していた。反応液を減圧下、ｏ−キシレンを留去し、減圧蒸留しＮ−シクロヘキシルマレイミド２３．９ｇを得た。収率５３．３％。 Comparative Example 2
To a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer, 14.7 g (150 mmol) of concentrated sulfuric acid and 50 ml of o-xylene are added, and nitrogen is allowed to flow into the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 2.8 ml of by-product water, the reaction solution was cooled to 70 ° C., 90 mg (0.75 mmol) of 4-methoxyphenol and 7.5 g (75 mmol) of cyclohexylamine were added, and then the reaction solution was refluxed. Then, a solution in which 25.0 g (250 mmol) of cyclohexylamine was added to 50 ml of o-xylene and a solution in which 25.0 g (250 mmol) of maleic anhydride was added to 50 ml of o-xylene were extracted while removing water for azeotropic distillation. It dripped simultaneously over time. After the dropwise addition, the mixture was further refluxed for 2 hours to separate about 2.7 ml of by-product water. After cooling the reaction solution to 10 ° C. or lower, the precipitated crystals were removed by filtration, and the reaction solution was washed 5 times with 100 ml of water. In the reaction liquid after washing, N-cyclohexylmaleimide corresponding to a yield of 64.0% was formed. Under reduced pressure, o-xylene was distilled off under reduced pressure and distilled under reduced pressure to obtain 23.9 g of N-cyclohexylmaleimide. Yield 53.3%.

比較例３
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸３．９ｇ（４０ｍｍｏｌ）、ｏ−キシレン２０ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約０．４ｍｌの副生水を確認後、反応液を７０℃まで冷却後、４−メトキシフェノール３０ｍｇ（０．２５ｍｍｏｌ）、トリエチルアミン２．０ｇ（２０ｍｍｏｌ）、無水マレイン酸２．０ｇ（２０ｍｍｏｌ）を添加し、次いで反応液を還流させながらＮ−シクロヘキシルマレアミド酸１９．３ｇ（９８ｍｍｏｌ）をｏ−キシレン６０ｍｌに加えた加温溶液を、共沸する水を抜き出しつつ３時間掛けて同時滴下した。滴下後さらに２時間還流し、約１．９ｍｌの副生水を分離した。反応液を２％重曹水溶液１００ｍｌで２回、次いで水１００ｍｌで５回洗浄した。洗浄後の反応液中には、収率６６．０％に相当するＮ−シクロヘキシルマレイミドが生成していた。 Comparative Example 3
Concentrated sulfuric acid (3.9 g, 40 mmol) and o-xylene (20 ml) were added to a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer, and nitrogen was allowed to flow into the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 0.4 ml of by-product water, the reaction solution was cooled to 70 ° C., and 30 mg (0.25 mmol) of 4-methoxyphenol, 2.0 g (20 mmol) of triethylamine, and 2.0 g (20 mmol) of maleic anhydride were added. Then, while the reaction solution was refluxed, a heated solution in which 19.3 g (98 mmol) of N-cyclohexylmaleamic acid was added to 60 ml of o-xylene was added dropwise simultaneously over 3 hours while extracting azeotropic water. After the dropwise addition, the mixture was further refluxed for 2 hours to separate about 1.9 ml of by-product water. The reaction solution was washed twice with 100 ml of 2% aqueous sodium bicarbonate solution and then 5 times with 100 ml of water. In the reaction solution after washing, N-cyclohexylmaleimide corresponding to a yield of 66.0% was formed.

比較例４
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸１９．６ｇ（０．２ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約３．６ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン２０．２ｇ（０．２ｍｏｌ）をキシレン１０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下し、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、キシレン１０ｍｌを添加し、次いで反応液を還流させながらシクロヘキシルアミン５０．０ｇ（０．５ｍｏｌ）をキシレン７０ｍｌに加えた加温溶液を、共沸する水を抜き出しつつ４時間掛けて同時滴下した。滴下後さらに１時間還流し、約４．２ｍｌの副生水を分離した。反応液は黒濁しており、水２００ｍｌを加えたところ多量のタール分が生成し分液操作はできなかった。 Comparative Example 4
Concentrated sulfuric acid (19.6 g, 0.2 mol) and xylene (100 ml) were added to a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, and thermometer, and nitrogen was allowed to flow through the reaction system. The mixture was refluxed while extracting azeotropic water. After confirming about 3.6 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 20.2 g (0.2 mol) of triethylamine to 10 ml of xylene was adjusted so that the temperature in the reaction system was 100 ° C. or less. Then, 36 mg (0.08 mmol) of copper dibutyldithiocarbamate, 55.0 g (550 mmol) of maleic anhydride and 10 ml of xylene were added, and then 50.0 g (0.5 mol) of cyclohexylamine was added to 70 ml of xylene while refluxing the reaction solution. The warmed solution added to was dripped simultaneously over 4 hours while removing azeotropic water. After the dropwise addition, the mixture was further refluxed for 1 hour to separate about 4.2 ml of by-product water. The reaction solution was black turbid, and when 200 ml of water was added, a large amount of tar was generated and the separation operation could not be performed.

比較例５
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた５００ｍｌ容の四つ口フラスコに、無水マレイン酸４９．０ｇ（０．５ｍｏｌ）、キシレン１６５ｇ、トルエン５４ｇを加え、反応系内に窒素を流しながら、シクロヘキシルアミン４７．６ｇ（０．４８ｍｏｌ）を３０℃で滴下し、滴下後１時間同温度で撹拌した。８５％リン酸９．２ｇ（８０ｍｍｏｌ）、Ｎ，Ｎ−ジメチルアニリン１．７ｇ（１４ｍｍｏｌ）を添加し、反応液を共沸する水を抜き出しつつ９時間還流させた。約７．４ｍｌの副生水を分離した。反応液は触媒相が分離しており、さらに不溶解分の生成がみられた。反応液を７０℃まで冷却後、ろ過で不溶解分を除去した。この反応液中には、収率４７．２％に相当するＮ−シクロヘキシルマレイミドが生成していた。 Comparative Example 5
To a 500 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer, 49.0 g (0.5 mol) of maleic anhydride, 165 g of xylene and 54 g of toluene were added. While flowing nitrogen, 47.6 g (0.48 mol) of cyclohexylamine was added dropwise at 30 ° C., followed by stirring at the same temperature for 1 hour. 9.2 g (80 mmol) of 85% phosphoric acid and 1.7 g (14 mmol) of N, N-dimethylaniline were added, and the reaction solution was refluxed for 9 hours while removing azeotropic water. About 7.4 ml of by-product water was separated. In the reaction solution, the catalyst phase was separated, and further insoluble matter was generated. The reaction solution was cooled to 70 ° C., and the insoluble matter was removed by filtration. In this reaction solution, N-cyclohexylmaleimide corresponding to a yield of 47.2% was formed.

実施例１〜４、比較例１〜５の製造方法について、目的物であるＮ−シクロヘキシルマレイミドの選択性を、「洗浄後の反応液中の目的物の収率」により評価した。
実施例１は、本発明で規定するように、酸触媒と、酸触媒に対して０．５モル当量の脱水助触媒（第三級アミン化合物）の存在下、無水マレイン酸を水と共沸可能な有機溶媒に溶解した溶液に、加熱還流下、脂肪族第一級アミン化合物であるシクロヘキシルアミンの溶液を供給し、均一反応系で脱水環化させた。洗浄後の反応液中には、目的物であるＮ−シクロヘキシルマレイミドが８８．５％に相当する好収率で含まれ、目的物を高選択的に得ることができた。
また、実施例２で示すように、実施例１で得られた、酸触媒および脱水助触媒を含有する洗浄水を再利用した場合にも、洗浄後の反応液中には、目的物であるＮ−シクロヘキシルマレイミドが９８．５％に相当する好収率で含まれ、目的物を高選択的に得ることができた。
さらに、実施例１に対して、脱水助触媒である第三級アミン化合物の種類を変えた実施例３及び４も、洗浄後の反応液中には、目的物であるＮ−シクロヘキシルマレイミドが順に８７．３％、８１．１％と好収率で含まれ、目的物を高選択的に得ることができた。
これに対して、本発明の規定を満たさない製造方法により製造した比較例１〜５は、いずれも、目的物であるＮ−シクロヘキシルマレイミドを高選択的に得ることができず、Ｎ−脂肪族置換マレイミド化合物の製造方法として劣っていた。
脱水助触媒としての第三級アミン化合物を使用しなかった比較例１では、洗浄後の反応液中の収率は６７．１％と低かった。脱水助触媒としての第三級アミン化合物に替えて第一級アミン化合物を使用した比較例２では、洗浄後の反応液中の収率は６４．０％、精製後の収率は５３．３％と低かった。また、脂肪族第一級アミン化合物に替えて前駆体マレアミド酸を滴下した比較例３では、洗浄後の反応液中の収率は６６．０％と低かった。
さらに、酸触媒に対して第三級アミン化合物を１．０モル当量と過剰に使用した比較例４では、多量のタール分が生成していて、目的物を分離することができなかった。
また、特開昭６２−１３８４６７号公報に記載の方法に準じた方法で、酸と第三級アミン化合物を触媒として、マレアミド酸を共沸脱水環化した比較例５では、反応液中の収率は４７．２％と低かった。
With respect to the production methods of Examples 1 to 4 and Comparative Examples 1 to 5, the selectivity of N-cyclohexylmaleimide as the target product was evaluated by “the yield of the target product in the reaction solution after washing”.
In Example 1, maleic anhydride was azeotroped with water in the presence of an acid catalyst and 0.5 molar equivalent of a dehydration cocatalyst (tertiary amine compound) relative to the acid catalyst as defined in the present invention. A solution of cyclohexylamine, which is an aliphatic primary amine compound, was supplied to a solution dissolved in a possible organic solvent under heating and reflux, and subjected to dehydration cyclization in a homogeneous reaction system. In the reaction solution after washing, N-cyclohexylmaleimide as the target product was contained in a good yield corresponding to 88.5%, and the target product could be obtained with high selectivity.
Further, as shown in Example 2, even when the washing water containing the acid catalyst and the dehydration cocatalyst obtained in Example 1 is reused, it is the target product in the reaction solution after washing. N-cyclohexylmaleimide was contained in a good yield corresponding to 98.5%, and the target product could be obtained with high selectivity.
Further, in Examples 3 and 4 in which the type of the tertiary amine compound that is a dehydration co-catalyst is changed from that in Example 1, the target N-cyclohexylmaleimide is sequentially added to the reaction solution after washing. It was contained in good yields of 87.3% and 81.1%, and the target product could be obtained with high selectivity.
On the other hand, none of Comparative Examples 1 to 5 produced by a production method that does not satisfy the provisions of the present invention can obtain the target N-cyclohexylmaleimide with high selectivity. It was inferior as a manufacturing method of a substituted maleimide compound.
In Comparative Example 1 in which the tertiary amine compound as a dehydration promoter was not used, the yield in the reaction solution after washing was as low as 67.1%. In Comparative Example 2 in which a primary amine compound was used instead of the tertiary amine compound as a dehydration promoter, the yield in the reaction solution after washing was 64.0%, and the yield after purification was 53.3. % Was low. In Comparative Example 3 in which the precursor maleamic acid was added dropwise instead of the aliphatic primary amine compound, the yield in the reaction solution after washing was as low as 66.0%.
Furthermore, in Comparative Example 4 in which the tertiary amine compound was used in an excess of 1.0 molar equivalent with respect to the acid catalyst, a large amount of tar was generated, and the target product could not be separated.
In Comparative Example 5 in which maleamic acid was subjected to azeotropic dehydration cyclization using an acid and a tertiary amine compound as a catalyst according to a method described in JP-A-62-2138467, the yield in the reaction solution was reduced. The rate was as low as 47.2%.

上記の通り、本発明で規定する製造方法によりＮ−シクロヘキシルマレイミドを製造した実施例１〜４は、いずれも目的物であるＮ−シクロヘキシルマレイミドを高選択的に得ることができた。また、本発明の製造方法によれば、実施例１及び２に記載するように、続く精製処理により、高純度のＮ−シクロヘキシルマレイミドを好収率で得ることができた（実施例１は純度９９．９％、収率８５．２％、実施例２は純度９９．６％、収率８５．１％）。   As described above, in Examples 1 to 4 in which N-cyclohexylmaleimide was produced by the production method defined in the present invention, N-cyclohexylmaleimide as the target product could be obtained with high selectivity. In addition, according to the production method of the present invention, as described in Examples 1 and 2, high-purity N-cyclohexylmaleimide could be obtained in a good yield by the subsequent purification treatment (Example 1 has purity). 99.9%, yield 85.2%, Example 2 purity 99.6%, yield 85.1%).

［２．各種Ｎ−脂肪族置換マレイミド化合物の製造］
以下、実施例５〜９の製造方法により、各種Ｎ−脂肪族置換マレイミド化合物を製造した。 [2. Production of various N-aliphatic substituted maleimide compounds]
Hereinafter, various N-aliphatic substituted maleimide compounds were produced by the production methods of Examples 5-9.

実施例５：Ｎ−ｎ−ブチルマレイミドの製造
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸９．８ｇ（０．１ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約１．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン５．１ｇ（５０ｍｍｏｌ）をキシレン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながらｎ−ブチルアミン３６．６ｇ（０．５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ３時間掛けて滴下した。滴下後さらに２時間還流し、約９．１ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで洗浄した。さらに、反応液を１．５％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。さらに反応液にジブチルジチオカルバミン酸銅０．１ｇ（０．２１ｍｍｏｌ）を加え、減圧下キシレンを留去した後、３ｍｍＨｇの減圧下、バス温を１１０〜１３０℃まで昇温し蒸留を行い、Ｎ−ｎ−ブチルマレイミドが５６．４ｇの無色オイルとして得られた。ＨＰＬＣ純度９９．２％、収率７３．７％。 Example 5: Production of Nn-butylmaleimide In a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, thermometer, 9.8 g (0.1 mol) of concentrated sulfuric acid, 100 ml of xylene was added and refluxed while extracting azeotropic water while flowing nitrogen into the reaction system. After confirming about 1.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 5.1 g (50 mmol) of triethylamine to 20 ml of xylene was added dropwise so that the temperature in the reaction system was 100 ° C. or less. . Maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and xylene 10 ml were sequentially added to the reaction system. Next, a solution obtained by adding 36.6 g (0.5 mol) of n-butylamine to 70 ml of xylene was dropped over 3 hours while extracting azeotropic water while refluxing the reaction solution. After the addition, the mixture was further refluxed for 2 hours to separate about 9.1 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of 1.5% aqueous sodium bicarbonate solution and then with 200 ml of water. Further, 0.1 g (0.21 mmol) of copper dibutyldithiocarbamate was added to the reaction solution, and xylene was distilled off under reduced pressure. After distillation under reduced pressure of 3 mmHg, the bath temperature was raised to 110 to 130 ° C. to perform distillation. n-Butylmaleimide was obtained as 56.4 g of a colorless oil. HPLC purity 99.2%, yield 73.7%.

実施例６：Ｎ−ｎ−ブチルマレイミドの製造
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸９．８ｇ（０．１ｍｏｌ）、トルエン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約１．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン５．１ｇ（５０ｍｍｏｌ）をトルエン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、トルエン１０ｍｌを順次加えた。次いで反応液を還流させながらｎ−ブチルアミン３６．６ｇ（０．５ｍｏｌ）をトルエン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ１４時間掛けて滴下した。滴下後さらに２時間還流し、約７．５ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液を水２００ｍｌで洗浄した。さらに、反応液を１％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。さらに反応液にジブチルジチオカルバミン酸銅０．１ｇ（０．２１ｍｍｏｌ）を加え、減圧下トルエンを留去した後、３ｍｍＨｇの減圧下、バス温を１１０〜１３０℃まで昇温し蒸留を行い、Ｎ−ｎ−ブチルマレイミドが５０．７ｇの無色オイルとして得られた。ＨＰＬＣ純度９６．９％、収率６６．２％。 Example 6: Production of Nn-butylmaleimide In a 300 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, thermometer, concentrated sulfuric acid 9.8 g (0.1 mol), Toluene (100 ml) was added, and refluxed while extracting azeotropic water while flowing nitrogen into the reaction system. After confirming about 1.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 5.1 g (50 mmol) of triethylamine to 20 ml of toluene was added dropwise so that the temperature in the reaction system became 100 ° C. or less. . Into the reaction system, maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and toluene 10 ml were sequentially added. Next, a solution obtained by adding 36.6 g (0.5 mol) of n-butylamine to 70 ml of toluene was added dropwise over 14 hours while extracting azeotropic water while refluxing the reaction solution. After dropping, the mixture was further refluxed for 2 hours to separate about 7.5 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, the reaction solution was washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of 1% aqueous sodium bicarbonate solution and then with 200 ml of water. Further, 0.1 g (0.21 mmol) of copper dibutyldithiocarbamate was added to the reaction solution, and toluene was distilled off under reduced pressure. After distillation under reduced pressure of 3 mmHg, the bath temperature was raised to 110 to 130 ° C. to perform distillation. n-Butylmaleimide was obtained as 50.7 g of a colorless oil. HPLC purity 96.9%, yield 66.2%.

実施例７：１，６−ビス（マレイミド）トリメチルヘキサン（２，２，４−および２，４，４−混合物）の製造
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸９．８ｇ（０．１ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約１．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン５．１ｇ（５０ｍｍｏｌ）をキシレン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながらトリメチルヘキサメチレンジアミン（東京化成、２，２，４−および２，４，４−混合物）３９．６ｇ（０．２５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ４時間掛けて滴下した。滴下後さらに１時間還流し、約９．４ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液にキシレン１５０ｍｌを加え、水２００ｍｌで洗浄した。さらに、反応液を２％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。キシレン相の不溶分をろ別後、減圧下キシレンを留去した後、メタノール２５０ｍｌを加え、加熱溶解後徐々に１０℃以下まで冷却し、析出した結晶をろ過乾燥し、１，６−ビス（マレイミド）トリメチルヘキサン（２，２，４−および２，４，４−混合物）が５６．３ｇの乳白色結晶として得られた。ＨＰＬＣ純度９８．８％、収率７０．３％。 Example 7: Preparation of 1,6-bis (maleimido) trimethylhexane (2,2,4- and 2,4,4-mixture) equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, thermometer To a 300 ml four-necked flask, 9.8 g (0.1 mol) of concentrated sulfuric acid and 100 ml of xylene were added, and refluxed while extracting azeotropic water while flowing nitrogen into the reaction system. After confirming about 1.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 5.1 g (50 mmol) of triethylamine to 20 ml of xylene was added dropwise so that the temperature in the reaction system was 100 ° C. or less. . Maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and xylene 10 ml were sequentially added to the reaction system. Then, while refluxing the reaction solution, a solution obtained by adding 39.6 g (0.25 mol) of trimethylhexamethylenediamine (Tokyo Kasei, 2,2,4- and 2,4,4-mixture) to 70 ml of xylene is azeotroped. It was added dropwise over 4 hours while draining water. After the addition, the mixture was further refluxed for 1 hour to separate about 9.4 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, 150 ml of xylene was added to the reaction solution and washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of 2% aqueous sodium bicarbonate solution and then with 200 ml of water. After filtering off the insoluble matter in the xylene phase, xylene was distilled off under reduced pressure, 250 ml of methanol was added, and after heating and dissolving, the mixture was gradually cooled to 10 ° C. or lower, the precipitated crystals were filtered and dried, and 1,6-bis ( Maleimido) trimethylhexane (2,2,4- and 2,4,4-mixture) was obtained as 56.3 g of milky white crystals. HPLC purity 98.8%, yield 70.3%.

実施例８：１−マレイミド−３−マレイミドメチル−３，５，５−トリメチルシクロヘキサン（位置異性体混合物）の製造
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた３００ｍｌ容の四つ口フラスコに、濃硫酸９．８ｇ（０．１ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約１．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン５．１ｇ（５０ｍｍｏｌ）をキシレン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながらイソホロンジアミン（東京化成、位置異性体混合物）３９．０ｇ（０．２５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ５時間掛けて滴下した。滴下後さらに３時間還流し、約９．１ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液に酢酸エチル４００ｍｌを加え、水２００ｍｌで洗浄した。さらに、反応液を３％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。有機相の不溶分をろ別後、減圧下溶媒を留去した後、メタノール１５０ｍｌを加え、加熱溶解後徐々に１０℃以下まで冷却し、さらに水を３０ｍｌ加え、析出した結晶をろ過乾燥し、１−マレイミド−３−マレイミドメチル−３，５，５−トリメチルシクロヘキサン（位置異性体混合物）が５１．９ｇの乳白色結晶として得られた。ＨＰＬＣ純度９５．２％、収率６５．６％。 Example 8: Preparation of 1-maleimido-3-maleimidomethyl-3,5,5-trimethylcyclohexane (mixture of positional isomers) 300 ml capacity equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube, thermometer. Concentrated sulfuric acid (9.8 g, 0.1 mol) and xylene (100 ml) were added to a four-necked flask, and the mixture was refluxed while extracting water to be azeotroped while flowing nitrogen into the reaction system. After confirming about 1.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 5.1 g (50 mmol) of triethylamine to 20 ml of xylene was added dropwise so that the temperature in the reaction system was 100 ° C. or less. . Maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and xylene 10 ml were sequentially added to the reaction system. Next, a solution obtained by adding 39.0 g (0.25 mol) of isophoronediamine (Tokyo Kasei, regioisomer mixture) to 70 ml of xylene was dropped over 5 hours while extracting azeotropic water while refluxing the reaction solution. After the dropwise addition, the mixture was further refluxed for 3 hours to separate about 9.1 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, 400 ml of ethyl acetate was added to the reaction solution and washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of 3% aqueous sodium bicarbonate solution and then with 200 ml of water. After filtering off the insoluble matter in the organic phase, the solvent was distilled off under reduced pressure, and then 150 ml of methanol was added. After dissolution by heating, the mixture was gradually cooled to 10 ° C. or lower, 30 ml of water was further added, and the precipitated crystals were filtered and dried. 1-maleimido-3-maleimidomethyl-3,5,5-trimethylcyclohexane (regioisomer mixture) was obtained as 51.9 g of milky white crystals. HPLC purity 95.2%, yield 65.6%.

実施例９：４，４’−ビスマレイミドジシクロヘキシルメタン（位置異性体混合物）の製造
マグネットスターラー、滴下ロート、ディーンスターク管、還流管、温度計を備えた５００ｍｌ容の四つ口フラスコに、濃硫酸１９．６ｇ（０．２ｍｏｌ）、キシレン１００ｍｌを加え、反応系内に窒素を流しながら、共沸する水を抜き出しつつ還流した。約３．８ｍｌの副生水を確認後、反応液を７０℃まで冷却後、トリエチルアミン１０．１ｇ（０．１ｍｏｌ）をキシレン２０ｍｌに加えた溶液を反応系内温度が１００℃以下になるように滴下した。反応系内に無水マレイン酸５５．０ｇ（５５０ｍｍｏｌ）、ジブチルジチオカルバミン酸銅３６ｍｇ（０．０８ｍｍｏｌ）、キシレン１０ｍｌを順次加えた。次いで反応液を還流させながら４，４’−ジアミノジシクロヘキシルメタン（東京化成、位置異性体混合物）５２．６ｇ（０．２５ｍｏｌ）をキシレン７０ｍｌに加えた溶液を、共沸する水を抜き出しつつ６時間掛けて滴下した。滴下後さらに２時間還流し、約８．６ｍｌの副生水を分離した。この時の反応液は均一で不溶分の生成もなかった。５０℃以下まで反応液を冷却後、反応液に酢酸エチル５００ｍｌを加え、水２００ｍｌで洗浄した。さらに、反応液を２％重曹水溶液２００ｍｌ、次いで水２００ｍｌで２回洗浄した。有機相の不溶分をろ別後、減圧下溶媒を留去し、粗４，４’−ビスマレイミドジシクロヘキシルメタン（位置異性体混合物）が９２．０ｇの淡黄色固体として得られた。ＨＰＬＣ純度８１．８％、収率９９．３％。 Example 9: Preparation of 4,4'-bismaleimide dicyclohexylmethane (mixture of regioisomers) Concentrated sulfuric acid was added to a 500 ml four-necked flask equipped with a magnetic stirrer, dropping funnel, Dean-Stark tube, reflux tube and thermometer. 19.6 g (0.2 mol) and 100 ml of xylene were added, and refluxed while extracting azeotropic water while flowing nitrogen into the reaction system. After confirming about 3.8 ml of by-product water, the reaction solution was cooled to 70 ° C., and a solution obtained by adding 10.1 g (0.1 mol) of triethylamine to 20 ml of xylene was adjusted so that the temperature in the reaction system was 100 ° C. or less. It was dripped. Maleic anhydride 55.0 g (550 mmol), copper dibutyldithiocarbamate 36 mg (0.08 mmol), and xylene 10 ml were sequentially added to the reaction system. Next, while refluxing the reaction solution, a solution in which 52.6 g (0.25 mol) of 4,4′-diaminodicyclohexylmethane (Tokyo Kasei, regioisomer mixture) was added to 70 ml of xylene was added for 6 hours while extracting azeotropic water. It was hung and dropped. After the addition, the mixture was further refluxed for 2 hours to separate about 8.6 ml of by-product water. The reaction solution at this time was uniform and no insoluble matter was produced. After cooling the reaction solution to 50 ° C. or lower, 500 ml of ethyl acetate was added to the reaction solution and washed with 200 ml of water. Further, the reaction solution was washed twice with 200 ml of 2% aqueous sodium bicarbonate solution and then with 200 ml of water. After insoluble components of the organic phase were filtered off, the solvent was distilled off under reduced pressure to obtain crude 4,4′-bismaleimide dicyclohexylmethane (regioisomer mixture) as 92.0 g of a pale yellow solid. HPLC purity 81.8%, yield 99.3%.

上記の通り、本発明で規定する製造方法により各種のＮ−脂肪族置換マレイミド化合物を製造した実施例５〜９は、いずれも目的物である各種のＮ−脂肪族置換マレイミド化合物を高選択的に得ることができ、また、精製処理により、目的物を高収率で得ることができた。
すなわち、本発明で規定する製造方法により、Ｎ−ｎ−ブチルマレイミドを製造した実施例５及び６は、精製処理により、高純度のＮ−ｎ−ブチルマレイミドを好収率で得ることができた（実施例５は純度９９．２％、収率７３．７％、実施例６は純度９６．９％、収率６６．２％）。いずれも、本発明の製造方法により、目的物であるＮ−ｎ−ブチルマレイミドを高選択的に得られたと考えられる。
また、本発明で規定する製造方法により、ジアミン化合物を原料とした場合にも、対応する二置換性Ｎ−脂肪族置換マレイミド化合物を高選択的に製造することができた（実施例７〜９）。
具体的には、実施例７は、１，６−ビス（マレイミド）トリメチルヘキサン（２，２，４−および２，４，４−混合物）を純度９８．８％、収率７０．３％で、実施例８は、１−マレイミド−３−マレイミドメチル−３，５，５−トリメチルシクロヘキサン（位置異性体混合物）を純度９５．２％、収率６５．６％で得ることができた。また、実施例９は、４，４’−ビスマレイミドジシクロヘキシルメタン（位置異性体混合物）を純度８１．８％、収率９９．３％でそれぞれ得ることができた。なお、実施例５〜９は、目的物が混合物で得られたため、「洗浄後の反応液中の目的物の収率」の、ＨＰＬＣでの定量分析は困難であった。 As described above, in Examples 5 to 9 in which various N-aliphatic substituted maleimide compounds were produced by the production method defined in the present invention, all the various N-aliphatic substituted maleimide compounds, which are target products, were highly selective. In addition, the target product could be obtained in a high yield by the purification treatment.
That is, in Examples 5 and 6 in which Nn-butylmaleimide was produced by the production method defined in the present invention, high-purity Nn-butylmaleimide could be obtained in good yield by purification treatment. (Example 5 has a purity of 99.2% and a yield of 73.7%, and Example 6 has a purity of 96.9% and a yield of 66.2%). In any case, it is considered that the target product, Nn-butylmaleimide, was obtained with high selectivity by the production method of the present invention.
Moreover, according to the production method defined in the present invention, even when a diamine compound was used as a raw material, the corresponding disubstituted N-aliphatic substituted maleimide compound could be produced with high selectivity (Examples 7 to 9). ).
Specifically, in Example 7, 1,6-bis (maleimido) trimethylhexane (2,2,4- and 2,4,4-mixture) was purified with a purity of 98.8% and a yield of 70.3%. Example 8 was able to obtain 1-maleimido-3-maleimidomethyl-3,5,5-trimethylcyclohexane (positional isomer mixture) with a purity of 95.2% and a yield of 65.6%. In Example 9, 4,4′-bismaleimide dicyclohexylmethane (regioisomer mixture) could be obtained in a purity of 81.8% and a yield of 99.3%, respectively. In Examples 5 to 9, since the target product was obtained as a mixture, it was difficult to quantitatively analyze the “yield of the target product in the reaction solution after washing” by HPLC.

本発明により、Ｎ−脂肪族置換マレイミド化合物の新規な工業的製造方法が提供される。
本発明の製造方法によれば、原料として、入手容易な一般式（１）で表される脂肪族第一級アミン化合物から、特殊な反応装置を用いることなく、穏やかな条件下、簡便な操作で、目的とする一般式（２）で表されるＮ−脂肪族置換マレイミド化合物を高選択的に効率製造でき、また、好収率で目的物を得られる。また、触媒若しくは遷移金属に由来する有害な廃棄物も排出しないので、廃棄物処理が容易で環境にも優しく、工業的な利用価値が高い。 The present invention provides a novel industrial production method for N-aliphatic substituted maleimide compounds.
According to the production method of the present invention, a simple operation can be carried out under mild conditions from a readily available primary aliphatic amine compound represented by the general formula (1) without using a special reaction apparatus. Thus, the target N-aliphatic substituted maleimide compound represented by the general formula (2) can be efficiently produced with high selectivity, and the target product can be obtained in good yield. In addition, since no harmful waste derived from the catalyst or transition metal is discharged, waste disposal is easy and environmentally friendly, and the industrial utility value is high.

Claims (6)

反応に使用する反応溶媒が水と共沸可能な有機溶媒のみから成り、
無水マレイン酸と、酸触媒と、脱水助触媒として該酸触媒に対し０．１５〜０．８モル当量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、下記一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給し、均一反応系で脱水環化させることを特徴とする、下記一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法。

（式中、Ｒはｎ価の脂肪族炭化水素基を示し、ｎは１〜６の整数である。） The reaction solvent used for the reaction consists only of an organic solvent that can be azeotroped with water,
In a solution containing maleic anhydride, an acid catalyst, 0.15 to 0.8 molar equivalent of a tertiary amine compound with respect to the acid catalyst as a dehydration cocatalyst, and an organic solvent azeotropic with water, An aliphatic primary amine compound represented by the following general formula (1) or a solution thereof is supplied under reflux with heating, and dehydration cyclization is performed in a homogeneous reaction system, which is represented by the following general formula (2). Of producing an N-aliphatic substituted maleimide compound.

(In the formula, R represents an n-valent aliphatic hydrocarbon group, and n is an integer of 1 to 6.) 前記脱水環化させた後の反応液を水で洗浄し、得られた水相を脱水した残留物を、前記の酸触媒および脱水助触媒またはそれらの一部として再利用することを特徴とする、請求項１に記載の製造方法。   The reaction solution after the dehydration cyclization is washed with water, and the residue obtained by dehydrating the obtained aqueous phase is reused as the acid catalyst and the dehydration promoter or a part thereof. The manufacturing method according to claim 1. 前記酸触媒が硫酸またはスルホン酸であることを特徴とする、請求項１又は２に記載の製造方法。   The production method according to claim 1, wherein the acid catalyst is sulfuric acid or sulfonic acid. 前記酸触媒の使用量が、前記脂肪族第一級アミン化合物に対し１．０モル当量未満であることを特徴とする、請求項１〜３のいずれか１項に記載の製造方法。   The production method according to any one of claims 1 to 3, wherein the amount of the acid catalyst used is less than 1.0 molar equivalent relative to the aliphatic primary amine compound. 無水マレイン酸と、酸触媒と、脱水助触媒として該酸触媒に対し０．１５〜０．８モル当量の第三級アミン化合物と、水と共沸可能な有機溶媒とを含有する溶液に、加熱還流下、下記一般式（１）で表される脂肪族第一級アミン化合物またはその溶液を供給し、均一反応系で脱水環化させ、
前記酸触媒を前記脂肪族第一級アミン化合物１モルに対し、０．４〜１．０モル使用するせることを特徴とする、下記一般式（２）で表されるＮ−脂肪族置換マレイミド化合物の製造方法。

（式中、Ｒはｎ価の脂肪族炭化水素基を示し、ｎは１〜６の整数である。） In a solution containing maleic anhydride, an acid catalyst, 0.15 to 0.8 molar equivalent of a tertiary amine compound with respect to the acid catalyst as a dehydration cocatalyst, and an organic solvent azeotropic with water, Under heating and reflux, an aliphatic primary amine compound represented by the following general formula (1) or a solution thereof is supplied, and dehydration cyclization is performed in a homogeneous reaction system.
An N-aliphatic substituted maleimide represented by the following general formula (2), wherein the acid catalyst is used in an amount of 0.4 to 1.0 mol with respect to 1 mol of the aliphatic primary amine compound. Compound production method.

(In the formula, R represents an n-valent aliphatic hydrocarbon group, and n is an integer of 1 to 6.) 前記第三級アミン化合物がトリアルキルアミンであることを特徴とする、請求項１〜５のいずれか１項に記載の製造方法。
The production method according to claim 1, wherein the tertiary amine compound is a trialkylamine.