JPH01283264A - Method for producing N-substituted maleimides - Google Patents

Abstract

PURPOSE:To obtain the subject substance in high purity and yield by carrying out the dehydrative cyclization imidation of maleic anhydride and amines or of maleic acid monoamides derived therefrom, in the presence of a catalyst in an organic solvent, washing the reaction mixture and separating and purifying the objective compound. CONSTITUTION:Maleic anhydride and an aromatic or aliphatic primary amine or a maleic acid monoamides derived therefrom are made to react in the presence of 5ppm-5wt.% of copper or a copper compound (e.g., cuprous oxide or copper acetate) and 0.2-25wt.% of a catalyst (e.g., sulfuric acid, benzenesulfonic acid or ion exchange resin) in an organic solvent at 70-160 deg.C. The reaction mixture is washed with a dilute aqueous solution of an alkali, water or a dilute aqueous solution of an acid and the N-substituted maleimides are separated from the organic layer. The reaction can be further accelerated by using a mixture of an aprotic polar solvent (e.g., DMF) and benzene, toluene, etc., as the organic solvent.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing N-substituted maleimides. More specifically, the present invention includes maleic anhydride and amines,
Alternatively, maleic acid monoamides obtained therefrom in an organic solvent in the presence of a catalyst.

The present invention relates to a method for producing N-substituted maleimides, in which a reaction mixture obtained by dehydration and ring-closing imidization is washed, and then isolated and purified.

N-substituted maleimides are compounds that have an extremely wide range of applications as medicines, agricultural chemicals, dyes, polymer raw materials, or intermediates thereof.

[Prior art]

Various methods have been known for producing N-substituted maleimides. For example, there is a method in which maleic acid monoamides (maleamic acids), which are easily obtained from maleic anhydride and amines, are heated to 180'C and subjected to dehydration cyclization to obtain N-substituted maleimides (L
, E. Coleman et al.

J, Org, Chem, 24135-136 (1959
)). However, with this method, the yield of the target product is 15~
It is as low as 50 cm.

In addition, a well-known laboratory method for producing is a method in which maleic anhydride and aniline are mixed in the presence of a sodium acetate catalyst and a dehydrating agent such as acetic anhydride is used (Org
, 5ynth, Co11. vol 5944(1
973)). This method has relatively high yield (75-80%)
However, since the dehydrating agent is used stoichiometrically, the cost of auxiliary raw materials is added and the production cost becomes high, making it unsuitable for industrial production.

On the other hand, a method considered to be advantageous as an industrial production method is a method in which maleic acid monoamides are dehydrated and cyclized under milder conditions using an efficient dehydration catalyst without using a dehydrating agent. Various attempts have been made to this method, including a method using an acidic catalyst such as sulfuric acid or sulfonic acid (British Patent No. 104
1027 specification), a method using a basic catalyst such as sodium hydroxide, triethylamine, etc. (Japanese Patent Publication No. 47-24
Many methods have been proposed, including a method using a heterogeneous catalyst such as an ion exchange resin (Japanese Patent Application Laid-open No. 85359/1983). Although these methods achieve a reaction yield of 90% or more, they are still insufficient in terms of suppressing side reactions, and the two reaction mixtures contain unreacted raw materials and Hatama bodies in addition to the catalyst.

Various side reaction products and polymers are included.

On the other hand, since N-substituted maleimides are used for purposes such as medicines, agricultural chemicals, and monomers, it is necessary to sufficiently remove impurities. Conventionally, the method for purifying N-substituted maleimides is to neutralize the reaction product with a dilute alkaline aqueous solution, wash it, and then isolate it by recrystallization or distillation.
-46394, JP-A-60-100554, JP-A-62-138468, etc.), or by acid treatment with a strong acid such as reactive sulfuric acid, converting the by-product into a resin and separating it, followed by washing with water and isolation. Method of
65, JP-A-61-204166/), etc. have been proposed.

However, the resin conversion method uses a large amount of acid and requires separating a sticky resin product, so the separation operation is not easy, and there are problems in terms of economy, operability, and waste. Also, the neutralization cleaning method.

There is a drawback that when the washing water layer is separated, the interface becomes emulsified or insoluble substances are precipitated, resulting in poor separation of by-products. This is a by-product that has an emulsifying effect due to a side reaction during the dehydration ring-closing imidization reaction.

This is due to the formation of by-products that are difficult to dissolve in organic solvents, and is due to poor selectivity of the two reactions. Therefore, if isolation operations such as distillation are performed with such by-products mixed in, polymerization is likely to occur simultaneously, resulting in a decrease in yield and purity. It is necessary to separate the emulsion layer by allowing it to stand for a long time, or to forcibly destroy the emulsion layer and remove insoluble matter by centrifugation or filtration, which complicates the cleaning process. There were problems such as: As described above, conventional purification techniques are still insufficient for industrial implementation.

[Problem to be solved by the invention]

-5= The present invention was made to solve the problems in conventional methods, and its purpose is to establish a method for producing N-substituted maleimides that can be carried out industrially advantageously, and furthermore, Specifically, by improving reaction selectivity and preventing the by-product of substances that cause separation deterioration during washing, it is possible to prevent polymerization during purification and obtain high-purity N-substituted maleimides in high yields. The object of the present invention is to establish a method for producing N-substituted maleimides that can be used. □ [Means for Solving the Problem] As a result of intensive research to achieve the above object, the present inventors have found that when maleic anhydride and primary amines or maleic acid monoamides obtained from them are dehydrated and ring-closed and imidized. The reaction is carried out in the coexistence of one or more copper or copper compounds.
It has been found that by neutralizing, washing with water, and isolating the product, highly purified N-substituted maleimides can be obtained in high yield without producing insoluble matter or emulsion layer by-products, and the reaction operation is extremely easy. We have arrived at the present invention.

To describe the gist of the present invention, the first invention is as follows:
Maleic anhydride and aromatic or aliphatic primary amines are heated in an organic solvent in the presence of copper or a copper compound and a catalyst to cause a dehydration ring closure reaction.

After washing the resulting reaction mixture with at least one selected from a dilute aqueous alkali solution, water, and a dilute aqueous acid solution,
This is a method for producing N-substituted maleimides, which comprises isolating the N-substituted maleimides from an organic layer.

The second invention involves heating maleic acid monoamides obtained by reacting maleic anhydride with an aromatic or aliphatic primary amine in an organic solvent in the presence of copper or a copper compound and a catalyst to perform cyclodehydration. N-substitution characterized in that the N-substituted maleimide is isolated from the organic i after the reaction mixture is washed with at least one selected from a dilute aqueous alkali solution, water and a dilute acid aqueous solution. This is a method for producing maleimides.

One embodiment of the present invention will be described below.

Maleic anhydride, which is the starting material of the present invention, may be obtained from any source; it is convenient to use an appropriately selected maleic anhydride from commercially available maleic anhydride. Also, using maleic acid.

Although the reaction proceeds in the same way, it cannot be said to be a good idea in terms of reactivity and economy. The other raw material, the primary amine, is an aromatic primary amine such as aniline, naphthylamine, toluidine, dimethylaniline, chloroaniline, and dichloroaniline.

Hydroxyaniline, nitroaniline, phenylenediamine, etc., preferably aniline, toluidine.

Chloraniline, dichloroaniline, hydroxyaniline, nitroaniline, etc., and aliphatic primary amines such as methylamine, ethylamine, propylamine, butylamine, benzylamine, cyclohexylamine, allylamine, ethylenediamine, etc., preferably methylamine, butylamine. and cyclohexylamine. The amount of maleic anhydride is 0.8 to 1.5 per mole of the primary amines.
It is preferable to use the range of 09 to 1.2.

The cyclodehydration reaction in the present invention is carried out in an organic solvent.

It is carried out in the presence of copper or a copper compound and a catalyst.

The first invention according to the present invention is to prepare maleic anhydride and the above-mentioned aromatic or aliphatic primary amines in an organic solvent,
It consists of heating in the presence of copper or a copper compound and a catalyst. This reaction can be carried out according to various methods, but a predetermined amount of maleic anhydride, primary amines, an organic solvent, copper or a copper compound, and a catalyst are charged into a reactor,
A method in which the reaction is carried out by heating to a predetermined temperature, or a predetermined amount of maleic anhydride, an organic solvent, copper or a copper compound, and a catalyst are placed in a reactor, heated to a predetermined temperature, and then primary amines are gradually added. method is preferable considering the operation method and others.

The organic solvent used in the present invention may be any solvent as long as it dissolves maleic anhydride, aromatic or aliphatic primary amines, and maleic acid monoamides and does not participate in the reaction, but preferably benzene, toluene,
Aromatic raw carbon-hydrogen solvents such as xylene, ethylbenzene, styrene, and cumene may be mentioned. Particularly preferred are benzene, toluene, and xylene-C-al.

There are no particular restrictions on the amount of organic solvent used, but it is subject to operability.

Considering economic efficiency, it is preferable to use it so that the product concentration is about 10 to 60%, particularly preferably 15 to 35%.
That's about it. Also as an organic solvent.

The reaction can be further promoted by using a mixture of the above-mentioned aromatic hydrocarbon solvent and an aprotic polar solvent. The aprotic polar solvents used in this case include formamide, N-methylformamide/dimethylformamide, dimethylacetamide/dimethylsulfoxide, and sulfolane.

Examples include γ-butyrolactone and hexamethylphosphotriamide. Preferred are dimethylformamide, dimethylacetamide, and dimethylsulfoxide.

The amount of the aprotic polar solvent used is arbitrary.

Usually 50% or less of the total amount of solvent, preferably 0.85 to 25%
Good condition.

The copper or copper compound used in the method of the invention is.

It improves reaction selectivity and suppresses the by-product of substances that cause deterioration in the separation of the washed water layer during purification. Copper or copper compounds include metallic copper such as copper powder and copper foil.

Copper oxides, sulfides and hydroxides such as cuprous oxide, cupric oxide/copper hydroxide, copper sulfide, cuprous chloride.

Cupric chloride, copper salt diisothermal copper compounds such as steel sulfate, steel nitrate, copper phosphate, copper complexes such as bisacetylacetonate steel, copper ethylenediaminetetraacetate, and organic copper such as copper acetate. Examples include compounds. In terms of thermal stability and economy, it is preferable to use metallic steel and inorganic copper compounds. These copper or copper compounds may be used alone or in combination of two or more.

There is no particular restriction on the amount of copper or copper compound used.

Usually, it is preferable to use it in a range of sppm to 5% by weight relative to the reaction solution. The amount of copper or copper compound used can be further reduced by combined use of an aprotic polar solvent.

Catalysts used in the present invention include sulfuric acid and sulfurous acid.

Inorganic acids such as sulfuric anhydride, phosphoric acid, sulfuric acid and boriphosphoric acid; organic acids such as benzenesulfonic acid, toluenesulfonic acid, benzenephosphonic acid, trichloroacetic acid and trifluoroacetic acid; and triethylamine.

Examples include organic bases such as pyridine, dimethylaniline and sodium acetate, and ion exchange resins such as 1 weakly acidic ion exchange resin and 1 weakly basic ion exchange resin, but preferably halosulfuric acid, phosphoric acid, and benzenesulfone. acids, toluenesulfonic acid, and ion exchange resins.

The amount of the catalyst to be used is not particularly limited, but it is usually in the range of 0.05% to 40% by weight, preferably 0.2% to 25% by weight based on the reaction solution.

The reaction temperature in the method of the present invention is generally in the range of 50 to 200°C, preferably in the range of 70 to 160°C. The reaction pressure is not particularly limited, and a wide range of normal pressure, increased pressure, and reduced pressure may be employed.

The reaction time varies depending on conditions such as raw material concentration, amount of catalyst, reaction temperature of solvent, etc., but is usually in the range of 0.5 to 10 hours.

The reaction mixture containing the N-substituted maleimide thus obtained is first washed, and then the N-substituted maleimide is isolated and purified from the resulting organic layer.

In the present invention, the reaction mixture is washed one or more times with at least one selected from dilute alkaline aqueous solution, water, and dilute acidic aqueous solution. As the dilute alkaline aqueous solution, an aqueous solution of an alkali metal or alkaline earth metal hydroxide, carbonate or hydrogen carbonate can be used, but an aqueous solution of a sodium or potassium hydroxide, carbonate or hydrogen carbonate is preferably used. be. Sulfuric acid is a dilute acidic aqueous solution.

Examples include aqueous solutions of sulfurous acid, phosphoric acid, sulfuric acid, hydrochloric acid, benzenesulfonic acid, toluenesulfonic acid, etc., and preferably an aqueous solution of sulfuric acid or phosphoric acid.

The amounts of these dilute alkaline aqueous solutions/water and dilute acidic aqueous solutions to be used are not particularly limited, but range from 10 to 10% of the amount of one reaction mixture.
Approximately 100 inches is preferable. As for cleaning.

The pH of the aqueous layer after washing is in the range of 0.5 to 8, preferably 1.
．． It is best to do this so that it falls within the range of 5 to 7. The washing temperature ranges from 20 to 90°C, preferably from 30 to 70°C.

In the washing operation, a washing aqueous solution is added to the reaction mixture, mixed and stirred for 5 minutes to 1 hour, and then left to stand to separate into two layers. At this time, with the conventional method, the separation performance is extremely poor and a non-uniform layer containing a large amount of emulsion and insoluble matter is formed at the interface of the two layers. 2.To improve the separation performance, it is necessary to leave it standing for a long time (over night or more) or centrifuge it. Alternatively, it was necessary to forcibly separate the emulsion and insoluble materials by passing through the mouth, etc.However, according to the method of the present invention, the two layers can be completely separated in a very short time (usually within 1 hour), so the operability is extremely high. Not only is it improved, but N-
An organic layer containing substituted maleimides can be obtained. Copper or a copper compound not only improves the selectivity of the reaction but also has a favorable effect on the separability of the washing water layer, so it may be added as necessary during washing.

Next, N is removed from the organic layer obtained by such a washing operation.
- Substituted maleimides are isolated according to known recrystallization or distillation methods.

In the case of the recrystallization method, it is preferable to use alcoholic solvents such as methanol, ethanol, and isopropanol, or aromatic solvents such as benzene, toluene, xylene, and styrene as the solvent for recrystallization separation.

In addition, in the case of distillation, it is preferable to carry out under normal pressure or reduced pressure. Since N-substituted maleimides have polymerizability, it is preferable to distill them at as low a temperature as possible2, usually under reduced pressure of 20 mmHg or less, preferably 10 mmHg or less.

In the second invention according to the present invention, the maleic acid monoamide obtained by reacting the above-mentioned maleic anhydride with an aromatic or aliphatic primary amine is subjected to a cyclodehydration treatment, and the dehydration ring is The chemical reaction treatment is carried out in the same manner as in the first invention. In this case, the maleic acid monoamide can be subjected to the cyclodehydration treatment without being isolated from the reaction product.

The synthesis reaction of maleic acid monoamides is preferably carried out in an organic solvent. As the organic solvent, the above-mentioned aromatic hydrocarbon solvent or a mixture thereof with an aprotic polar solvent is used. This reaction easily proceeds at a reaction temperature of about 150° C. or lower without using any particular catalyst. The reaction temperature is suitably from room temperature to 100°C. The reaction time varies depending on the reaction temperature, solvent, etc., but is suitably 0.5 to 24 hours.

The washing treatment of the reaction mixture obtained by the dehydration cyclization reaction and the isolation treatment of the N-substituted maleimide can be carried out in the same manner as in the case of the first invention.

Since both the raw material and the product in the method of the present invention have polymerization-active double bonds, it is effective to use a polymerization inhibitor in one reaction and purification step.

There is no limit to the effects of the present invention. Hydroquinone and metquinphenol are used as polymerization inhibitors.

Effective examples include t-butylcatechol, phenothiazine, thiourea, hydroxyquinoline, cuperone, and N-nitrosodiphenylamine.

EXAMPLES Hereinafter, the structure and effects of the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 107.8 gr of maleic anhydride was placed in a reactor equipped with a reflux condenser equipped with a water separator, a thermometer/stirrer, and a dropping funnel.
) toluene 400 ml dimethylformamide 25
m1p-) luenesulfonic acid5. Q l/r + copper sulfate 0.11r and p-methoxyphenol 0.2 Fi
Add r and heat to dissolve while stirring. Next, 93.1 aniline was added from the dropping funnel! ilr was added dropwise, and the mixture was reacted for 3 hours under reflux of the solvent. Water generated during the reaction is removed from a water separator. After the reaction was completed, one reaction solution was analyzed by gas chromatography and found to be 172. The production of IJ N-phenylmaleimide was confirmed.

The reaction yield was 99.41.

Next, the reaction solution was cooled to 60° C., 6% aqueous sodium carbonate solution 20011r was added thereto, the mixture was stirred and mixed for 20 minutes, and the aqueous layer was separated into two layers using a quiet device for 20 minutes, and the aqueous layer was removed. The resulting organic layer was kept at 50°C.

Again with 1001r of dilute sulfuric acid aqueous solution adjusted to pH 2.

After washing in the same manner, the aqueous layer was separated. In both of these two washing operations, no emulsion layer or insoluble matter was formed at the interface during separation, and both the organic layer and the aqueous layer were homogeneous and transparent liquids. After removing the solvent from the washed organic layer using HII in 130 to 20 dishes,
Distillation was carried out over a period of 3 hours at a bath temperature of 160°C and a reduced pressure of 9 mmHy. As a result, N-7 enylmaleimide of 165,21r was obtained (pale yellow solid with melting point of 89-90°C, yield of 95.4%, purity of 99.9% by gas chromatography analysis).

Comparative Example 1 The same operation as in Example 1 was carried out except that copper sulfate was not added, and the reaction yield was 96.1%. Also, 129.2,9r N-7 enylmaleimide was obtained. (pale yellow solid, melting point 80-90°C, yield 74.6%, purity 99.6% by gas chromatography). In addition,
During the washing operation, an emulsion layer containing insoluble matter was produced at 15 mJ in the first wash and 120 ml in the first wash.

Comparative Example 2 The same operation as in Example 1 was performed except that dimethylformamide and sulfuric acid steel were not added.

A yellow slurry-like reaction solution was obtained with a reaction yield of 87.4%, but in the second washing step, the whole became an emulsion-like solution containing yellow-white insoluble matter, and the experiment was discontinued because the aqueous layer hardly separated. .

Comparative Example 3 Example 1 except that dimethylformamide was not added
When exactly the same operation as above was carried out, 1 reaction yield of 87.91 and 104.4 # of N-7 enylmaleimide was obtained (pale yellow solid with melting point of 89-90°C, yield of 60.3%).
・Purity 99.8%).・During the cleaning operation, the emulsion layer containing insoluble matter was rated at 12 mA for the first cleaning! - The second wash produced 8 ml.

Example 2 In a reactor similar to Example 1, 10.3% of maleic anhydride was added.
0.1 iTr, 200 ml of xylene, 10 mJ of dimethyl sulfoxide, 98% sulfuric acid3. 0.051 ir of Ofir copper powder and 0.111 ir of hydroquinone are charged and heated and dissolved while stirring. Next, 93.1 fir of aniline was added dropwise from a 2-dropping funnel, and the mixture was reacted for 2 hours under reflux of the solvent. Water produced during the reaction is removed through a water separator. After the reaction was completed, one reaction solution was analyzed by gas chromatography, and the result was 170.0. The production of N-phenylmaleimide of P was confirmed. The reaction yield at this time was 98.
It was 2 chi.

Next, the first reaction solution was cooled to 50° C., 4.5% IJium aqueous solution 2001r was added thereto, the mixture was stirred and mixed for 20 minutes, and the aqueous layer was separated into two layers using a quiet device for 10 minutes, and the aqueous layer was removed. The obtained organic layer was kept at 50° C. and washed again in the same manner with a dilute aqueous phosphoric acid solution IoOSR adjusted to pH 1.5, and the aqueous layer was separated. No formation of an emulsion layer or insoluble matter was observed during washing and separation. After desolventizing the washed organic layer with 130-20 mm HIi, 400 ml of Improper Tool heated to 70°C was added, and 70-7
Dissolve at 5°C. Then, while stirring slowly, 10
Cool to ℃.

The precipitated crystals were taken out and washed with 100 ml of Improper Tool. The recrystallization mother liquor and the washed isopropanol were combined, concentrated to about 50 inA', cooled again to 10°C, and the precipitated crystals were washed on the mouth side to obtain 1 second crystal. The primary and secondary crystals were combined and dried with hot air at 70°C for 1 hour.
-Phenylmaleimide 163,1 fir was obtained (pale yellow solid with melting point 89-90°C, yield 94.2%, purity 99%).
．． 9%).

Examples 3-4 0-chloroaniline 127.6.1i as primary amine
The same procedure as in Example 1 was carried out, except that lr or o-toluidine 107.2.9'r was used, cupric oxide 0.111r was used as the copper compound, and the distillation pressure was changed. I got the result.

21 Example 5 Maleic anhydride 107.8 was added to the same reactor as Example 1.
gr,) toluene 400ml 1l dimethylformamide 25
m1・Ion exchange resin Anno (-List 15■ (manufactured by O-M &-1%-S) 501Ir, 0.2 IT of copper acetate, and 0.2 fir of p-methoxyphenol are charged and dissolved by heating with stirring. Next, 73.11/r of n-butylamine was added dropwise from the dropping funnel and reacted for 6 hours under reflux of the solvent.Water produced during the reaction was removed from the water separator.After the reaction was completed, the mixture was cooled to 60°C. The catalyst was separated and washed with toluene.The reaction yield was 84.7 cm as determined by gas chromatography analysis.

Next, one reaction solution was kept at 60°C, and 300 ml of a 6% aqueous sodium carbonate solution and 10 ml of a dilute sulfuric acid aqueous solution adjusted to pH 2 were added.
Washing was carried out twice in the same manner as in Example 1 using 0 mA'. No emulsion layer or insoluble matter was observed during washing and separation.The obtained organic layer was heated at 130 to 20 mmH, ii
After desolvation with l, bath temperature of 90 °C * 6 mmH, l
Distillation was carried out for 3 hours at a + degree of vacuum.

As a result, 123.51 ir of N-n-butylmaleimide was obtained (boiling point 86-89°C/6 mmI (J
i+ colorless transparent liquid, yield 80.6cm, purity 99.5%
).

Example 6 Maleic anhydride 107.8 was added to a reactor similar to Example 1.
1/r, ) 400 ml of Rue, 25 ml of dimethylformamide + 0.1 gr of copper sulfate, and 0.2 gr of p-methoxyphenol are charged and dissolved with stirring. Next, add 93% of aniline from the dropping funnel. I Fir was added dropwise over 1 hour while keeping the reaction temperature below 40°C, and the mixture was further aged at 40°C for 1 hour with stirring. After adding p-)luenesulfone [5,0,9r to the obtained maleanilic acid slurry solution, a dehydration reaction was carried out for 3 hours while the produced water was azeotropically removed under reflux. The reaction yield by gas chromatography analysis was 93.5%.

Next, this reaction solution was subjected to the same post-treatment as in Example 1, and 154.4 gr of N-phenylmaleimide was obtained (pale yellow solid with a melting point of 89-90°C, yield 89.2%).
, purity 99.8%). Incidentally, during the washing operation, no formation of an emulsion layer was observed at all in both the first and second washing operations.

Comparative Example 4 The same operation as in Example 6 was performed except that copper sulfate was not added, and the reaction yield was 90.8% and 116.8#.
N-phenylmaleimide of r was obtained (melting point 88-9
Pale yellow solid at 0°C, yield 67.5%.

purity 99.1%). In addition, during the washing operation, an emulsion layer containing insoluble matter was produced in an amount of 60 ml in the first washing and 120 ml in the second washing.

〔Effect of the invention〕

According to the method of the present invention, highly purified N-substituted maleimides can be obtained in high yield. Further, the present invention has the following advantages.

1) Separability during washing is significantly improved and operability is improved.

II) Yields in reaction and purification are improved.

111) Product purity is improved.

lv) Purification is easy as by-products are reduced.

■) Polymerization during purification can be prevented.

Claims (2)

[Claims] (1) Maleic anhydride and an aromatic or aliphatic primary amine are heated in an organic solvent in the presence of copper or a copper compound and a catalyst to cause a cyclodehydration reaction, and the resulting reaction mixture is dissolved in a dilute aqueous alkaline solution. A method for producing an N-substituted maleimide, which comprises isolating the N-substituted maleimide from an organic layer after washing with at least one selected from , water, and a dilute aqueous acid solution. (2) Maleic acid monoamides obtained by reacting maleic anhydride with an aromatic or aliphatic primary amine are heated in an organic solvent in the presence of copper or a copper compound and a catalyst to cause a cyclodehydration reaction; The resulting reaction mixture is mixed with at least one selected from a dilute aqueous alkaline solution, water, and a dilute aqueous acid solution.
A method for producing N-substituted maleimides, which comprises isolating the N-substituted maleimides from an organic layer after washing with seeds.