JPH0525129A - Production of n-substituted maleimides - Google Patents

Abstract

PURPOSE:To produce an N-substituted maleimide in high yield in a shortened reaction time with suppressing side reactions such as polymerization by one- stage reaction. CONSTITUTION:At least 1.05mol, based on 1mol aromatic or aliphatic primary amine, of maleic anhydride is subjected to ring formation reaction through dehydration in the presence of an acid catalyst in an organic solvent, then the reaction solution is washed with 0.5-5 times as much water as the excessive amount of maleic anhydride by weight, separated into an organic layer containing maleimides and a water layer and then the water layer is recycled and fed in an aqueous solution as it is to the reaction process.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing N-substituted maleimides. N-substituted maleimides are used for medicines, agricultural chemicals,
The compound has a very wide range of use as a dye, a polymer raw material or an intermediate thereof.

[0002]

2. Description of the Related Art As a method for producing N-substituted maleimides, various methods have been conventionally known. For example, there is a method in which maleic acid monoamides (maleamic acids) obtained by the reaction of maleic anhydride and amines are heated to 180 ° C. and subjected to dehydration cyclization to obtain N-substituted maleimides (LE Coleman et al. J. Org. Chem.
24 135-136 (1959)). However, according to this method, the yield of the desired product is as low as 15 to 50%.

[0003] in the presence of sodium acetate catalyst of maleic acid monoamides, there is a method using a dehydrating agent such as acetic anhydride (Org. Synth. Coll. Vol 5 944 (1973)).
Although this method can obtain N-substituted maleimides in a relatively high yield (75 to 80%), it uses a dehydrating agent in a stoichiometric amount, so that a raw material cost is added and a manufacturing cost is high. And is unsuitable as an industrial production method.

On the other hand, a method which is considered to be advantageous as an industrial production method is a method in which a dehydrating cyclization of maleic acid monoamides is carried out under milder conditions using an efficient dehydrating catalyst without using a dehydrating agent. .. Various attempts have also been made to this method, a method using an acidic catalyst such as sulfuric acid and sulfonic acid (GB 1041027), sodium hydroxide,
Many methods have been proposed, such as a method using a basic catalyst such as triethylamine (Japanese Patent Publication No. 47-24024) and a method using a heterogeneous catalyst such as an ion exchange resin (Japanese Patent Laid-Open No. 61-85359). .. According to these methods, the reaction yield reaches 90% or more, but it is not always sufficient in terms of suppressing side reactions, and by-products such as side reaction products and polymers are by-produced, resulting in a purification step and product purity. Have an adverse effect. Further, since the maleic acid monoamides become a concentrated slurry at the initial stage of the reaction, there is a problem in terms of reaction operability.

As a method for improving these problems, maleic anhydride is allowed to gradually react with primary amines in the presence of an acid catalyst in an organic solvent without precipitation of an intermediate maleic acid monoamide. A method for synthesizing N-substituted maleimides in one step has been proposed (Japanese Patent Laid-Open No. 60-11465).
JP-A-62-273952). According to this method, it is an indispensable condition to gradually add the primary amines so that the intermediate maleic acid monoamides will not be precipitated. Therefore, there is a drawback that the reaction time becomes long in order to increase the yield. is there. Prolonging the reaction time not only becomes extremely industrially disadvantageous because it impairs the efficiency of the reaction apparatus and also increases the utility, and polymerization during the reaction,
There is also an unfavorable problem in terms of reaction because it causes an increase in side reactions such as intermolecular condensation and cis-trans rearrangement.

The reaction time is usually shortened by increasing the reaction temperature and the amount of catalyst, but the former causes an increase in side reactions such as polymerization, and the latter causes an increase in the purification process burden and an increase in auxiliary raw material costs. It is not an effective means because it accompanies it.

[0007]

As described above, in the synthesis reaction of maleimides by the dehydration cyclization reaction in the presence of a catalyst, the reaction proceeds in a shorter time with good operability, and the side reaction is suppressed to give a yield, It is an important issue to improve product purity.

The present invention has been made to meet the above-mentioned demands in the technical field of the related art, and its object is to provide a method for producing N-substituted maleimides which can be industrially advantageously carried out. More specifically, when producing N-substituted maleimides by a one-step reaction, the reaction time is shortened, side reactions such as polymerization are suppressed, and N-substituted maleimides are obtained in high yield. The point is to provide a method for producing N-substituted maleimides that can be produced.

[0009]

The present invention is directed to the reaction of maleic anhydride with an aromatic or aliphatic primary amine to produce N-substituted maleimides in the presence of an acid catalyst. The maleic anhydride was used in a solvent in an amount of at least 1.05 times the molar amount of the primary amines to carry out a dehydration cyclization reaction, and then the reaction solution was added with an excess amount of maleic anhydride of 0.5.
An N-substituted maleimide characterized by being washed with 5 to 5 times by weight of warm water to separate it into two layers, an organic layer containing a maleimide and an aqueous layer, and then circulating the aqueous layer as an aqueous solution to the reaction step. Related to the manufacturing method of the class.

The present invention will be described in detail below. The maleic anhydride that is the starting material of the present invention may be obtained from any source, and it is convenient to use an appropriately selected maleic anhydride that is commercially available. Further, even when maleic acid is used, the reaction proceeds similarly, but it is not a good idea from the viewpoint of reactivity and economical efficiency.

The primary amine which is the other raw material includes aromatic primary amines such as aniline, naphthylamine, toluidine, dimethylaniline, chloroaniline, dichloroaniline, nitroaniline and phenylenediamine, and aliphatic primary amines. Examples of the monoamines include methylamine, ethylamine, propylamine, butylamine, benzylamine, cyclohexylamine, allylamine, and ethylenediamine.

The amount of maleic anhydride and primary amines used is at least 1.05 times, preferably 1.1 to 2.0 times the molar amount of maleic anhydride with respect to the primary amines. used.

The reaction between maleic anhydride and primary amines is carried out in an organic solvent in the presence of an acid catalyst. As the organic solvent, maleic anhydride, aromatic or aliphatic primary amines and the maleic acid monoamide of the intermediate, and may be anything as long as it does not participate in the reaction,
Aromatic hydrocarbon solvents such as benzene, toluene, xylene, ethylbenzene, styrene and cumene are preferably used. Particularly preferred are benzene, toluene and xylene. The amount of the organic solvent used is not particularly limited, but the product concentration is 10 to 6 in consideration of operability and economy.
It is preferable to use it so as to be about 0%, preferably 15
It is about 35%.

The reaction can be further promoted by using the above-mentioned aromatic hydrocarbon solvent mixed with an aprotic polar solvent as the organic solvent. Examples of the aprotic polar solvent include formamide, N-methylformamide, dimethylformamide, dimethylacetamide, dimethylsulfoxide, sulfolane, γ-butyrolactone, N-methylpyrrolidone and hexamethylphosphotriamide. Preferred are dimethylformamide, dimethylacetamide and dimethylsulfoxide. The amount of the aprotic polar solvent used is arbitrary, but usually 50% or less of the total amount of solvent, preferably 0.5 to 2
About 5% is good.

The catalyst used in the method of the present invention includes:
Inorganic acids 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, trifluoroacetic acid, and strongly acidic ion exchange resins,
Examples thereof include ion exchange resins such as weakly acidic ion exchange resins, but sulfuric acid, phosphoric acid, benzenesulfonic acid, toluenesulfonic acid, strong acidic ion exchange resins and the like are preferable. Although the amount of the catalyst used is not particularly limited, it is usually used in the range of 0.05% by weight to 40% by weight, preferably 0.2% by weight to 25% by weight, based on the reaction solution. Further, a metal such as copper or zinc or a metal compound as a reaction aid may be used in combination with the above catalyst.

The reaction temperature in the method of the present invention is usually 5
It is applied in the range of 0 to 200 ° C, preferably 70 to 160 ° C. The reaction pressure is not particularly limited and is widely applied to normal pressure, increased pressure and reduced pressure. The reaction time can be considerably short and is usually applied in the range of 0.5 to 8 hours, preferably in the range of 1 to 5 hours.

The method of practicing the present invention is usually carried out as follows. In an organic solvent or a mixed solvent with an aprotic polar solvent, an acid catalyst and maleic anhydride, and optionally a reaction auxiliary agent are added, and the mixture is heated to a temperature above the azeotropic point of water and the solvent, and then the primary amine is gradually added. Add to. At that time, the desorbed water generated by the reaction is introduced together with the azeotropic solvent into the reflux condenser and continuously removed from the reaction solution by the water separator. After the addition of the primary amine is completed, the reaction is completed when the generation of desorbed water stops.

After the reaction is completed, the reaction solution is washed. As the washing operation, a specific amount of warm water is added to the reaction solution, and the mixture is mixed and stirred for 5 minutes to 1 hour, and then allowed to stand to separate into two layers of an organic layer and an aqueous layer. As a result, in addition to the excess unreacted maleic anhydride, a water-soluble reaction aid such as an acid catalyst and an aprotic polar solvent is recovered from the reaction solution in the water layer. This aqueous layer is then reused in the reaction.

The amount of water used for washing is the difference between the amount of maleic anhydride used (mol) and the amount of primary amines (mol) used in the reaction,
That is, it is applied in a range of 0.5 to 5 times the weight of maleic anhydride in excess. When the amount of water is less than 0.5 times, it is insufficient to transfer all the unreacted maleic anhydride and the water-soluble reaction aid to the aqueous layer, and the cleaning efficiency is reduced. If the amount is more than 5 times, there are problems in reaction such as increase of side reaction due to increase of water in the reaction system and decrease of yield when the water layer is circulated in the reaction system, and water evaporation amount is increased. The increase in utility due to the increase is also not economically preferable. The cleaning temperature is 30 ° C to 100 ° C.
Particularly, the range of 40 ° C to 80 ° C is suitable.

The aqueous layer thus obtained is circulated and supplied as an aqueous solution to the reaction step. At that time, the aqueous solution may be supplied all at once to a solution of an organic solvent of maleic anhydride, or may be added and supplied simultaneously with the primary amines.

On the other hand, the reaction product N-substituted maleimide is isolated by distillation or recrystallization after the solvent is distilled off from the organic layer. In the case of the distillation method, it is preferable to carry out the reaction under normal pressure or reduced pressure. Since the N-substituted maleimide has polymerizability, distillation at a temperature as low as possible is preferable, and distillation under a reduced pressure of usually 20 mmHg or less, preferably 10 mmHg or less is preferable. In the case of the recrystallization method, as a solvent, an alcohol solvent such as methanol, ethanol, isopropanol, or benzene, toluene, xylene,
It is recommended to recrystallize and separate using an aromatic solvent such as styrene.

Since both the raw material and the product in the method of the present invention have a polymerization-active double bond, it is effective to use a polymerization inhibitor in the reaction and purification steps. As the polymerization inhibitor, hydroquinone, methoxyphenol, t-butylcatechol, phenothiazine, thiourea, hydroxyquinoline, cuperone, N-nitrosodiphenylamine and the like are effective.

In the present invention, by carrying out the reaction by the above method, the reaction rate is increased, the reaction time is shortened, the production of by-products is suppressed, and the N-substituted maleimides are produced in high yield. Can be manufactured. Also,
The aqueous solution after washing the reaction solution has an advantage that it can be reused as it is in the reaction step.

Usually, in a dehydration equilibrium reaction such as this reaction,
Mixing water into the reaction system causes inhibition of the reaction and increase of by-products, resulting in a decrease in yield, which is not a preferable method. However, in the method of the present invention, the dehydration cyclization reaction is hardly adversely affected by the aqueous solution that is circulated and supplied, and rather, the advantage of recycling and reuse of excess unreacted raw materials and water-soluble reaction aids is utilized, which is short. Reaction progresses in time,
Moreover, it is unexpected that the N-substituted maleimide can be produced in a high yield.

[0025]

EXAMPLES The present invention will be described below with reference to examples. Example 1 127.4 g of maleic anhydride in a reactor equipped with a reflux condenser equipped with a water separator, a thermometer, a stirrer and a dropping funnel.
(1.3 mol), 400 ml of toluene, 15 ml of dimethylformamide, 5.0 g of p-toluenesulfonic acid and 0.1 g of copper sulfate are charged and heated with stirring. Under solvent reflux (1
Aniline 93.1 g from the dropping funnel at 10 to 120 ° C)
(1.0 mol) was added dropwise over 1 hour. After the completion of aniline dropping, the mixture was aged at the same temperature for 1 hour. Water generated during dropping and aging is removed by a water separator. After the reaction was completed, the yellow transparent reaction liquid was analyzed by gas chromatography, whereupon it was confirmed that 170.6 g of N-phenylmaleimide had been formed. The reaction yield was 98.5%. Next, the reaction solution was cooled to 70 ° C., 30 g of warm water was added, and the mixture was stirred for 5 minutes. After standing, 74.0 g of an aqueous layer separated into two layers was separated and collected. 2 as maleic anhydride in the recovered water layer
It contained 9 g (0.29 mol). On the other hand, the organic layer was washed with 100 ml of a 1% sodium carbonate aqueous solution and then with 50 ml of dilute sulfuric acid having a pH of 2, and then distilled under reduced pressure. As a result, 165.2 g of N-phenylmaleimide was obtained (pale yellow solid having a melting point of 89 to 90 ° C., yield 95.4).
%, Purity by liquid chromatography 99.9
%). The solvent recovered during vacuum distillation and the recovered aqueous layer obtained by washing the reaction solution were returned to the reactor, and 98.1 g (1.0 mol) of maleic anhydride was added, and then the solvent was refluxed (110 to 120 ° C.). Aniline 93.1 from the dropping funnel
g (1.0 mol) was added dropwise over 1 hour, and the above operation was repeated. The reaction yield was 98.2%, and 163.9 g of N-phenylmaleimide was obtained (melting point). 89-90 ° C pale yellow solid, yield 94.6%, purity 99.9%).

Comparative Example 1 The reaction was carried out in the same manner as in Example 1 except that the amount of maleic anhydride used was 98.1 g (1.0 mol) and the washing operation with warm water was not performed, and aniline was added dropwise for 20 minutes. After that, a pale yellowish white solid was deposited and the reaction solution became a slurry.
After completion of the reaction, analysis revealed that the reaction yield was 73.6%, and 115.7 g of N-phenylmaleimide was obtained (pale yellow solid having a melting point of 87 to 90 ° C., yield 66.
8%, purity 98.7%).

Comparative Example 2 According to the method of Example 1, except that the amount of maleic anhydride used was 98.1 g (1.0 mol), the dropping time was 4 hours, the aging time was 2 hours, and the warm water washing operation was not performed. When the reaction was conducted, the reaction yield was 93.1%, and it was 144.4.
g of N-phenylmaleimide was obtained (melting point 88-
90 ° C pale yellow solid, yield 83.4%, purity 99.
6%).

Example 2 The reaction was carried out according to the method of Example 1 except that the amount of maleic anhydride used was 107.8 g (1.1 mol), the dropping time was 2.5 hours, and the aging time was 1 hour. As a result, the initial reaction yield was 98.2%, and 165.4 g of N-phenylmaleimide was obtained (pale yellow solid having a melting point of 89 to 90 ° C., yield 95.5%, purity 99.9). %). In addition, recovered water layer (55.2 g: 9 g as maleic anhydride)
The second reaction yield after recycling (containing 0.09 mol) was 98.5%, and 165.7 g of N-phenylmaleimide was obtained (pale yellow solid having a melting point of 89 to 90 ° C., Yield 95.7%, purity 99.9%).

Example 3 Maleic anhydride 147.2 was placed in the same reactor as in Example 1.
g, toluene 400 ml, dimethyl sulfoxide 20 ml,
3.0 g of 98% sulfuric acid and 0.1 g of copper sulfate are charged and heated with stirring. Aniline 93.1 g (1.0 mol) was added dropwise over 1 hour from the dropping funnel under solvent reflux (110 to 120 ° C.). After the aniline addition is complete, continue at the same temperature for 3
Aged for 0 minutes. Water generated during dropping and aging is removed by a water separator. After the reaction was completed, the yellow reaction solution was analyzed by gas chromatography to find that it was 172.0 g.
It was confirmed that N-phenylmaleimide was produced. The reaction yield was 99.3%. Next, the reaction liquid was cooled to 80 ° C., 50 g of warm water was added, and the mixture was stirred for 5 minutes. After standing, 114.3 g of an aqueous layer separated into two layers was separated and collected. The recovered aqueous layer contained 49 g (0.5 mol) of maleic anhydride. On the other hand, the organic layer is a 1% sodium carbonate aqueous solution 10
After washing with 0 ml and then with 50 ml of dilute sulfuric acid of pH 2, each was distilled under reduced pressure. As a result, 165.9 g of N-
Phenylmaleimide was obtained (pale yellow solid having a melting point of 89 to 90 ° C., yield 95.8%, purity by liquid chromatography 99.9%). The solvent recovered at the time of vacuum distillation and the recovered aqueous layer obtained by washing the reaction solution were returned to the reactor, and 98.1 g (1.0 mol) of maleic anhydride was added, and then the solvent was refluxed (110 to 12 ° C). ) 93.1 g (1.0 mol) of aniline was added dropwise from the dropping funnel over 1 hour, and the above-mentioned operation was repeated. The reaction yield was 9
8.6% and 164.9 g of N-phenylmaleimide were obtained (pale yellow solid, mp 89-90 ° C,
Yield 95.2%, purity 99.9%).

Examples 4 to 5 127.6 g of o-chloroaniline as the primary amine
(1.0 mol) or 107.2 g of o-toluidine
When the reaction was performed according to the method of Example 1 except that (1.0 mol) was used, the results shown in Table 1 were obtained.

[Table 1]

Example 6 Maleic anhydride 147.2 was added to a reactor similar to that of Example 1.
g (1.5 mol), toluene 400 ml, dimethylformamide 25 ml, copper sulfate 0.1 g, p-methoxyphenol 0.2 g and ion exchange resin Amberlyst 15 (made by Rohm & Haas) 50 g, and heated with stirring Dissolve. Then, under solvent reflux (110 to 120 ° C.), n
-Butylamine 73.1 g (1.0 mol) was added dropwise over 2 hours. After the completion of aniline dropping, the mixture was aged at the same temperature for 1 hour. Water generated during dropping and aging is removed by a water separator. After completion of the reaction, the reaction solution is cooled to 70 ° C., the ion exchange resin is filtered off, and washed with toluene. When analyzed by gas chromatography, 127.9 g
The formation of Nn-butylmaleimide was confirmed. The reaction yield was 83.5%. Next, the reaction liquid was kept at 70 ° C., 50 g of warm water was added, the mixture was stirred for 5 minutes, and after standing, 113.1 g of an aqueous layer separated into two layers was separated and collected. The recovered aqueous layer contained 51 g (0.52 mol) of maleic anhydride. On the other hand, the organic layer is a 1.5% sodium carbonate aqueous solution 1
Each was washed with 00 ml and then with 50 ml of dilute sulfuric acid of pH 1.5 and distilled under reduced pressure. As a result, 120.7 g of N
-N-Butylmaleimide was obtained (boiling point 86-89
C./6 mmHg colorless transparent liquid, yield 78.8%, purity by liquid chromatography 99.7%). The solvent recovered at the time of vacuum distillation, the recovered aqueous layer obtained by washing the reaction solution and the recovered ion exchange resin were returned to the reactor, and 98.1 g (1.0 mol) of maleic anhydride was added, and then the solvent was refluxed ( Aniline 9 from the dropping funnel at 110-120 ° C)
When 3.1 g (1.0 mol) was added dropwise over 2 hours and the above-mentioned operation was repeated, the reaction yield was 91.2%, and 129.9 mol of N-n-butylmaleimide were obtained. A colorless transparent liquid having a boiling point of 86 to 89 ° C./6 mmHg, yield 84.8%, purity 99.6% was obtained.

[0032]

According to the method of the present invention, the reaction is effectively carried out in a short time, and the N-substituted maleimides can be produced in high yield. Further, the present invention has the following advantages. (I) The reaction rate is improved, and the reaction time is significantly shortened. (Ii) Generation of by-products such as polymers is suppressed. (Iii) The yield of the desired product is improved. (Iv) Purification is easy because there are few by-products. (V) It is possible to circulate and reuse the aqueous solution containing the unreacted raw materials and the reaction aid after washing the reaction solution. (Vi) Waste is greatly reduced.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number in the agency FI technical display location // C07B 61/00 300 (72) Inventor Masahiro Ushigome 10-1 Daikokucho, Tsurumi-ku, Yokohama-shi, Kanagawa Issue Nitto Chemical Industry Co., Ltd.

Claims (1)

Claim: What is claimed is: 1. When an N-substituted maleimide is produced by reacting maleic anhydride with an aromatic or aliphatic primary amine, in the presence of an acid catalyst in an organic solvent. The maleic anhydride is subjected to a cyclodehydration reaction in an amount of at least 1.05 times the primary amines, and then the reaction solution is treated with an excess amount of warm water 0.5 to 5 times the weight of maleic anhydride. A method for producing N-substituted maleimides, which comprises washing to separate into two layers, an organic layer containing maleimides and an aqueous layer, and then circulatingly supplying the aqueous layer as an aqueous solution to a reaction step.