JPH0774198B2 - Method for purifying N-substituted maleimides - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for purifying N-substituted maleimides. More specifically, the present invention is a reaction mixture containing N-substituted maleimides obtained by dehydration ring-closure imidization of maleic anhydride and amines or maleic acid monoamides obtained therefrom in the presence of a catalyst in an organic solvent. To purify by washing and distillation.

N-substituted maleimides are compounds having a very wide range of applications as medicines, agricultural chemicals, dyes, polymer raw materials, or intermediates thereof.

[Prior art]

Conventionally, as a method for purifying N-substituted maleimides, a method of injecting a reaction solution into a large amount of cold water, separating precipitated crystals, and washing the crystals with a larger amount of water or an organic solvent (Organi)
c Synthesis Coll.V944 (1973)), after neutralizing and washing with a dilute aqueous solution of sodium carbonate, the organic layer is separated,
A method of distilling off the solvent (Japanese Patent Publication No. 55-46394), a method of acid-treating with a strong acid such as sulfuric acid after the reaction to make a by-product into a resin and separating it, followed by washing with water (Japanese Patent Laid-Open No. 61-22065 and 61-22065). JP-A-61-204166), cleaning with a dilute alkaline aqueous solution,
A method has been proposed in which it is washed again with water, the solvent is distilled off, and the product is recrystallized from an alcoholic solvent (JP-A-60-100554). However, in the method as described above, the by-product generated in the dehydration ring-closure imidization step is insoluble in water and cannot be sufficiently removed during washing, and it is difficult to obtain high-purity N-substituted maleimides. In addition, the recrystallization method from alcohol also causes side reactions with reconstituted solvents and multiple mergers,
It is difficult to obtain high-purity products in high yield.

On the other hand, as a method for purifying N-substituted maleimides, a purification method by distillation has been carried out (JP-A-60-112758 and JP-A-60-112759). However, since maleimides are monomers having an ethylenic double bond, they are easily polymerized when heated during distillation, and thus the distillation yield also decreases. In order to prevent such a decrease in yield due to polymerization during distillation, a method of distilling in the presence of a stabilizer (JP-A-61-29862) or a method of neutralizing with an alkaline earth metal compound and then distilling (JP-A-61-29826) 62-
No. 138468) has been proposed, but polymerization cannot be completely prevented yet.

As described above, the conventional refining techniques are not sufficient to prevent impurities such as by-products or to prevent the occurrence of multiple mergers during distillation, have problems in yield and product purity, and are still unsuitable as industrial methods. It is insufficient.

[Problems to be Solved by the Invention]

The present invention has been made to solve the problems in the conventional method, and an object thereof is to provide a method for purifying N-substituted maleimides that can be industrially advantageously carried out, and more specifically, Provided is a method for purifying N-substituted maleimides capable of sufficiently removing impurities such as by-products, preventing the occurrence of multiple mergers during distillation, and obtaining high-purity N-substituted maleimides in high yield. It is a thing.

[Means for Solving the Problems]

As a result of earnest research to achieve the above object, the present inventors have found that N
The present invention was found by discovering that highly pure N-substituted maleimides can be obtained in high yield by washing a reaction mixture containing -substituted maleimides and then distilling the mixture in the presence of phosphorus oxyacids.

The gist of the present invention is to describe a reaction mixture containing N-substituted maleimides, which comprises reacting maleic anhydride with an aromatic or aliphatic primary amine.
1 selected from dilute alkaline solution, water and dilute acid solution
It is a method for purifying N-substituted maleimides, which comprises washing the organic layer obtained by washing once or more with seeds one or more times and then distilling the obtained organic layer in the presence of phosphorus oxyacids.

Embodiments of the present invention will be described below.

The starting material of the present invention, maleic anhydride, may be obtained from any source, and it is convenient to use an appropriately selected maleic anhydride commercially available. Further, even when maleic acid is used, the reaction and purification proceed in the same manner, but it is not a good idea from the viewpoint of reactivity, economy and the like.

Examples of the aromatic primary amines as the other raw material include aniline, naphthylamine, toluidine, dimethylaniline, chloroaniline, dichloroaniline, nitroaniline and phenylenediamine, and aliphatic primary amines include, for example, Methylamine, ethylamine, propylamine, butylamine, benzylamine,
Examples thereof include cyclohexylamine, allylamine, ethylenediamine and the like.

The primary amines and maleic anhydride are used in a molar ratio.
It is used in the range of 1: 0.8 to 1.5, preferably 1: 0.9 to 1.2. The N-substituted maleimide reaction mixture used in the present invention is prepared by subjecting the above maleic anhydride and primary amines, or maleic acid monoamides obtained by reacting them to dehydration ring-closure imidization in an organic solvent in the presence of a catalyst. can get.

At this time, the catalyst used is an inorganic acid such as sulfuric acid, sulfurous acid, sulfuric anhydride, phosphoric acid, phosphorous acid, polyphosphoric acid,
Organic acids such as benzenesulfonic acid, toluenesulfonic acid, benzenephosphonic acid, trichloroacetic acid and trifluoroacetic acid, organic bases such as triethylamine, pyridine, dimethylaniline and sodium acetate, and strongly acidic ion exchange resins, weakly acidic ion exchange resins, Examples thereof include ion exchange resin catalysts such as weakly basic ion exchange resins, but sulfuric acid, phosphoric acid, benzene sulfonic acid, toluene sulfonic acid, and ion exchange resins are preferable. Any reaction catalyst may be used as long as it dissolves N-substituted maleimides, forms an azeotropic mixture with water, and is inert and does not participate in the reaction, but is preferably benzene, toluene, xylene, ethylbenzene or chloro. Examples include benzene. The amount of the organic solvent used is not particularly limited, but it is preferable that the concentration of the product is about 10 to 60% in consideration of operability and economy.

Further, as the organic solvent, an aprotic polar solvent may be mixed with the above water azeotropic solvent and used. Formamide and N are used as aprotic polar solvents.
-Methylformamide, dimethylformamide, dimethylacetamide, dimethylsulfoxide, sulfolane,
Examples include γ-butyrolactone and hexamethylphosphoramide. Although the amount of the aprotic polar solvent used is arbitrary, it is usually preferably about 2 to 30% of the total amount of the solvent.

The reaction temperature is usually in the range of 50 to 200 ° C, particularly preferably 70 to 1
It is in the range of 60 ° C.

In the synthesis of these N-substituted maleimides,
It does not matter even if a polymerization inhibitor such as hydroquinone, methoxyphenol, t-butylcatechol, phenothiazine, thiourea, hydroxyquinoline, cuperone, N-nitrosodiphenylamine is used together.

When maleic acid monoamides obtained by reacting maleic anhydride with aromatic or aliphatic primary amines are subjected to the above dehydration ring-closure imidization reaction, maleic acid monoamides are separated from the reaction product. The dehydration ring-closing treatment can be carried out without separation. The synthesis reaction of this maleic acid monoamide is preferably carried out in an organic solvent. As the organic solvent, those mentioned above are used. This reaction easily proceeds at a reaction temperature of about 150 ° C. or lower without using a catalyst. The reaction temperature is from room temperature to 100
Up to ℃ is suitable.

The reaction mixture containing the N-substituted maleimides thus obtained is first washed and then purified by distillation in the presence of phosphoric acid.

The washing is performed once or more with one or more kinds of dilute alkaline aqueous solution, water or dilute acid aqueous solution. Preferably, it is preferable to first wash with a dilute aqueous alkali solution and then, if necessary, rewash with water and a dilute aqueous acid solution once or more. Wash the water layer after separation
It is preferable to perform it so that the pH is in the range of 8 to 0.5.

For the washing with a dilute alkaline aqueous solution, an aqueous solution of various basic substances can be used, but sodium or potassium hydroxide, in consideration of washability, operability, and economic efficiency,
Preference is given to using carbonates or hydrogen carbonates. It is preferable to use a dilute alkaline aqueous solution having a concentration in the range of 1 to 20% by weight.

Aqueous solutions of various acidic substances can be used for washing with a dilute acid aqueous solution, but sulfuric acid and phosphoric acid are preferably used in consideration of washability, operability, economy and the like. The concentration of the dilute aqueous acid solution is preferably pH 0.1 to 5. The amount of these washing liquids used is not particularly limited, but is preferably about 10 to 100% of the amount of the reaction mixture liquid. The washing temperature is 20 to 90 ° C, preferably 30 to 70 ° C.

Next, the organic layer obtained by such a washing operation is distilled in the presence of phosphoric acid. Examples of the phosphorous oxygen acid used here include inorganic phosphorous oxygen acids such as phosphoric acid, phosphorous acid, hypophosphorous acid, metaphosphoric acid, pyrophosphoric acid, condensed phosphoric acid, polyphosphoric acid, and phenylphosphonic acid and phenylphosphinic acid. Organophosphoric oxygen acids, preferably phosphoric acid, phosphorous acid and phenylphosphonic acid. These phosphorus oxyacids can also be used in the form of acidic salts. These phosphorus oxyacids are added after the washing and prior to distillation. The amount used is in the range of 0.01 to 10% by weight, preferably 0.05 to 5% by weight, based on the N-substituted maleimide.

Distillation is carried out under normal pressure or reduced pressure. Since N-substituted maleimides have polymerizability, distillation at a temperature as low as possible is preferable. Therefore, it is usually preferable to distill under reduced pressure of 20 mmHg or less, preferably under reduced pressure of 10 mmHg or less.

Hereinafter, the configuration and effects of the present invention will be described more specifically with reference to Examples, but the present invention is not limited to these Examples.

Example 1 A reactor equipped with a reflux condenser equipped with a water separator, a thermometer, a stirrer and a dropping funnel was charged with 107.8 g of maleic anhydride, 400 ml of xylene, 25 ml of dimethylformamide, and 5.0 g of P-toluenesulfonic acid. Heat and dissolve under stirring. Then, 93.1 g of aniline was added dropwise from the dropping funnel over 1 hour, and then the reaction was carried out under solvent reflux for 2 hours. Water generated during the reaction is removed from the water separator. After completion of the reaction, the reaction liquid (yellow transparent liquid) was analyzed by gas chromatography, and it was confirmed that 167.1 g of N-phenylmaleimide was produced (reaction yield 96.5%).

Next, the reaction solution was cooled to 50 ° C., 200 g of a 6% sodium carbonate aqueous solution was added thereto for washing, and the aqueous layer was separated. At this time, the pH of the aqueous layer was 6.9. The obtained organic layer was desolvated at a temperature of 60 to 110 ° C and a pressure of 130 to 20 mmHg after adding 0.5 g of 85% phosphoric acid, and then at a bath temperature of 160 ° C and a pressure reduction degree of 9 mmHg.
Distilled over time. As a result, 160.6 g of N-phenylmaleimide was obtained (yellow solid having a melting point of 89 to 90 ° C, yield 9
2.7%, purity by gas chromatography 99.4%).
The remaining amount of the distillation still at this time was 7.3 g.

Comparative Example 1 By the same procedure as in Example 1 except that 85% phosphoric acid was not added, 81.6 g of N-phenylmaleimide was obtained (yellow solid having a melting point of 88 to 90 ° C., yield). 47.1%, purity by gas chromatography 98.6%). The remaining amount of the distillation still at this time was 88.6 g.

Examples 2 to 3 In the distillation operation, the same operation as in Example 1 was carried out except that 0.5 g of phosphorous acid or 1.0 g of phenylphosphonic acid was used as the phosphorous oxygen acid, and the results in Table 1 were obtained.

Example 4 After the dehydration ring-closure imidization reaction and the washing with a dilute alkaline aqueous solution were carried out in the same manner as in Example 1, the pH of the obtained organic layer was kept at 50 ° C.
It was washed again with 100 g of diluted sulfuric acid aqueous solution adjusted to 2, and the aqueous layer was separated. The pH of the aqueous layer at this time was 3.1.

Next, after adding 85% phosphoric acid 0.2 g to the obtained organic layer,
Desolvation was performed at a temperature of 60 to 110 ° C and a pressure of 130 to 20 mmHg, then 16
Distillation was carried out at a bath temperature of 0 ° C. and a pressure reduction degree of 9 mmHg for 3 hours. As a result, 163.1 g of N-phenylmaleimide was obtained (yellow solid having a melting point of 89 to 90 ° C., yield 94.2%, purity by gas chromatography 99.9%). The remaining amount of the distillation still at this time was 1.8 g.

Examples 5-6 127.6 g of o-chloroaniline as primary amine or o
-Using 107.2 g of toluidine, the same operation as in Example 1 was carried out except that the distillation pressure was changed, and the results shown in Table 2 were obtained.

Example 7 107.8 g of maleic anhydride, 400 ml of toluene, 25 ml of dimerformamide and 50 g of ion exchange resin Amberlyst 15 ^R (manufactured by Rohm & Haas) were charged in the same reactor as in Example 1 and dissolved by heating under stirring. .

Then, 73.1 g of n-butylamine was added dropwise from the dropping funnel over 1 hour, and then the reaction was carried out under solvent reflux for 5 hours. Water generated during the reaction is removed from the water separator. After completion of the reaction, the mixture is cooled to 60 ° C, the catalyst is separated by filtration, and washed with toluene. When the reaction liquid (light brown liquid) was analyzed by gas chromatography, formation of 117.8 g of Nn-butylmaleimide was confirmed (reaction yield 76.9%).

Next, keep the reaction solution at 60 ° C, and add 6% sodium carbonate aqueous solution.
It was washed with 250 g and the aqueous layer was separated. At this time, the pH of the water layer is
It was 5.2. The obtained organic layer was kept at 60 ° C., washed again with 100 g of a dilute phosphoric acid aqueous solution adjusted to pH 1.5, and the aqueous layer was separated. The pH of the aqueous layer at this time was 2.0. 8 in the resulting organic layer
After adding 0.4g of 5% phosphoric acid, the temperature is 60-110 ℃, the pressure is 130.
The solvent was removed at .about.20 mmHg and then distilled at a bath temperature of 90.degree. C. and a pressure reduction degree of 6 mmHg for 3 hours. As a result, 114.1g of N-
n-Butylmaleimide was obtained (boiling point 86-89 ° C / 6mmHg
Colorless transparent liquid, yield 74.5%, purity by gas chromatography 99.2%). The remaining amount of the distillation still at this time was 4.5 g.

Examples 8 to 9 In the washing operation, the same operation as in Example 1 was carried out except that 200 g of dilute sulfuric acid aqueous solution having a pH of 3 or 200 g of water was used as a washing liquid, and the results shown in Table 3 were obtained.

[Effect of the Invention] According to the purification method of the present invention, N-substituted maleimides having a purity of about 99% or more can be obtained with a purification yield of about 95% or more. Further, the present invention has the following advantages.

i) The distillation yield is significantly improved.

ii) It is possible to prevent the occurrence of multiple mergers during distillation.

iii) The remaining amount of the kettle after distillation can be significantly reduced.

iv) Product purity is improved.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ken Narita 10-1 Daikokucho, Tsurumi-ku, Yokohama-shi, Kanagawa Nitto Chemical Industry Co., Ltd. (72) Yuya Yano 10-10, Oguro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa No. 1 Nitto Chemical Industry Co., Ltd. Examiner Shoei Hoshino

Claims (1)

[Claims] 1. A reaction mixture containing N-substituted maleimides, which is obtained by reacting maleic anhydride with an aromatic or aliphatic primary amine, is selected from a dilute aqueous alkali solution, water and a dilute aqueous acid solution. A method for purifying N-substituted maleimides, which comprises washing one or more times with one or more times, and then distilling the obtained organic layer in the presence of phosphorus oxyacids.