JPH0421668A - Production of n-substituted maleimides - Google Patents

Abstract

PURPOSE:To obtain the subject compounds which are raw materials for medicines, agricultural chemicals, etc., in high purity by reacting maleic anhydride with an aromatic or an aliphatic primary amine in the coexistence of a copper- and a phosphorus-based compounds in an organic solvent capable of forming an azeotropic mixture with water under specific conditions in reacting both. CONSTITUTION:Maleic anhydride is made to react with an aromatic or an aliphatic primary amine as raw materials. In the process, imidating reaction is carried out in an organic solvent (preferably an aromatic hydrocarbon such as benzene or toluene preferably used at a concentration so that the theoretical concentration of the reaction product may be 20-50wt.%), capable of forming an azeotropic mixture with water in the coexistence of a copper compound, and at least one phosphorus-based compound at 50-200 deg.C while azeotropically distilling formed water with the aforementioned organic solvent and discharging the water to the outside of the reaction system. Thereby, the objective compounds are obtained. Furthermore, aniline, etc., are preferred as the primary amine and an organocopper compound is preferred as the copper compound.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing N-substituted maleimides useful as raw materials for medicines, agricultural chemicals, dyes, and polymers.

(Prior Art) Various methods have been known for producing maleimides. For example, r Org, 5ynth
Co11. J, vol. 5, p. 944, 1973.
describes a method of dehydrating maleic acid monoamides obtained by reacting maleic anhydride with amines in the presence of a catalyst using a chemical dehydrating agent such as acetic anhydride. This method has a relatively high yield (75
~80%) N-substituted maleimides can be obtained. However, since it is necessary to use a dehydrating agent such as acetic anhydride in a stoichiometric manner depending on the amount of water to be produced, it has the disadvantage that the manufacturing cost is high.

In order to solve this drawback and provide an industrially advantageous production method, a production method that does not use a chemical dehydrating agent such as acetic anhydride has been reported. For example, Tokuko Sho 51-4
No. 0078 discloses that maleic anhydride and J primary amine are oxidized in the presence of an acid catalyst such as sulfur trioxide or sulfuric acid.
For example, a method is described in which the ring is closed by heating and dehydration in a solvent having a boiling point of 80° C. or higher, such as toluene, bovine silone, or chlorobenzene. In this method, produced water is azeotroped with a solvent and then discharged. This method is advantageous in terms of production cost because it does not use a large amount of expensive dehydrating agent. However, because the reaction temperature is high.

For example, side reactions such as the production of polymeric by-products due to polymerization of N-substituted maleimides once produced within one reaction system are likely to occur. Therefore, according to this method.

There are problems in that the yield and product purity of the N-substituted maleimides obtained are low, and further purification steps are required, making the manufacturing process complicated. Furthermore, according to this method, the reaction solution is colored brown during the second reaction, and the maleimides obtained are also colored even after the purification step, and the utility value of the product is low.

JP-A-1-316767 discloses a method of using hindered phenols, which are common phenolic polymerization inhibitors, to inhibit the polymerization of maleimides. However, such general phenolic polymerization inhibitors do not have a sufficient effect of inhibiting polymerization, and are also insufficient in inhibiting coloring of a single reaction system.

Other common polymerization inhibitors include 2, for example.

Copper powder and copper compounds used as polymerization inhibitors for acrylic acid-based compounds are known ("Acrylic acid and its polymer [I] - Industrial use as raw material -", Shokodo Co., Ltd.). When such a copper compound is applied to the synthesis of maleimides, the polymerization inhibiting effect (1) is slightly superior to that of the above-mentioned phenolic polymerization inhibitor, but the reaction system (2) is more colored than when the phenolic polymerization inhibitor is used.

(Problems to be Solved by the Invention) The present invention solves the above-mentioned conventional drawbacks, and its purpose is to solve the following problems: Ni! In the production of substituted maleimides, side reactions can be effectively suppressed, and N-substituted maleimides with high purity and good color can be produced in high yield, and as a result,
An object of the present invention is to provide a method for producing N-substituted maleimides that can simplify the purification process.

(Means for Solving the Problems) The present invention provides a method for producing N-substituted maleimides using maleic anhydride and an aromatic or aliphatic primary amine as raw materials, the method comprising: grade amine,
In an organic solvent that is azeotropic with water.

In the coexistence of a copper compound and at least one phosphorous compound, the imidization reaction is carried out at a temperature of 50 to 200"C while the water produced is azeotropically distilled with the organic solvent and discharged out of the reaction system. - A method for producing N-substituted maleimides, which achieves the above object.

Specific examples of primary amines that can be used in the method of the invention include aniline, toluidine, dimethylaniline, ethylaniline, diethylanilinecarboxyaniline,
Aromatic primary amines such as hydroquineaniline, chloroaniline, dichloroaniline, bromoaniline, dibromoaniline, tribromoaniline, nitroanione or fats such as methylamine, ethylamine, hexylamine, octylamine, laurylamine, benzylamine cyclohexylamine Primary amines of the group include group primary amines. In particular, the N-substituted maleimides obtained are likely to be colored,
The method of the present invention is effective when aniline, toluidine, ethylaniline, etc. are used.

Maleic anhydride and the above primary amine are primary amino 1
0.8 to 1.5 mol, preferably 0.9 to 1.5 mol
It is used in a proportion of 1.3 moles.

The organic solvent used in the method of the invention is capable of dissolving maleic anhydride and an aromatic or aliphatic primary amine;
At temperatures between 50 and 200°C, the produced water can be discharged from the system as an azeotrope. It is an inert organic solvent. Aromatic hydrocarbons such as benzene, toluene, and xylene are preferably used. The amount of these organic solvents used is not particularly limited.

From the viewpoint of operability and economy, the concentration is preferably such that the theoretical concentration of one reaction product is 10 to 60% by weight, preferably 20 to 50% by weight. For the purpose of improving the solubility of the reaction components, it is also possible to use an aprotic polar solvent such as dimethylformamide, dimethylacetamide, dimethylsulfoxide, etc., if necessary. The amount of these aprotic polar solvents to be used is also not particularly limited, but is preferably about 1 to 30% by weight based on the total amount of solvent.

The copper compound used in the present invention is metallic copper.

Copper oxide, copper hydroxide, copper sulfide, copper chloride, copper sulfate, copper nitrate,
Inorganic copper compounds such as copper phosphate; and copper acetate, copper oxyacetate, copper propiolate, copper valerate.

Copper citrate, copper hexate, copper gluconate, copper salicylate, copper caprylate, copper pelargonic acid, copper sebacate,
Copper valmitate, copper oleate, copper stearate, copper bisglycinate, copper bisacetylacetonate, copper bisaminobenzenesulfonate.

Copper bisleucine, bis(copper ethyl acetoacetate,
Examples include organic copper compounds such as.

In particular, organic copper compounds are preferably used. Two or more of these copper compounds may be used in combination.

As the phosphorus compound used in the present invention, R5PR3P
Phosphoranes represented by the formula =CR2; Phosphines represented by the formula RsP and phosphonium salts derived from these, for example, Phosphonium salts represented by the formula R4PCI: Phosphine sulfides represented by the formula RsP-X Bosphin oxides; R2P-□R, R2P(X)
Phosphinites, phosphinone thioates, and phosphinates represented by the XR formula (7); RP (OR>2.
Examples include phosphonites, phosphonothionites, and phosphonates represented by the formula RP(X) (OR>2); and phosphites and thiophosphites represented by the formula P(XR)3.

Here, X is independently an oxygen atom or a sulfur atom, and R is H or an aliphatic or aromatic hydrocarbon group of 01 to CI8.

Examples of the above phosphoranes represented by the formula RsP, R3P=CR2 include pentaphenylphosphorane.

Examples include triphenyldiphenylmethylenephosphorane.

The above phosphines represented by the formula RsP include:

flltT? , triphenylphosphine, and tribenzylphosphine.

It is represented by the formula R3P=X. Examples of the phosphine sulfides include triphenylphosphine sulfide, and examples of the phosphine oxides include triphenylphosphine oxide.

R2P-OR, R2P (X) XR The above phosphinites, phosphinodithioates,
Examples of phosphinates include phenyldiphenylphosphinite and diphenylphosphinodithioi.

Examples include quacid, diphenylphosphinic acid, and their esters such as phenyldiphenylphosphinodithioate and phenyldiphenylphosphinate.

RP (OR > 2. RP ( Examples include phenylphosphonic acid, 0.0-diphenylphenylphosphonothioate, and diphenylphenylphosphonate.

The above phosphites represented by the formula P(XR) 3 Examples of thiophosphites include moro-butyl phosphite, diphenyl phosphite, tri-n-butyl phosphite, triphenyl phosphite, tri-benzyl phosphite, and tri-butyl phosphite. Examples include octyl trithiophosphite, trilauryl trithiophosphite, trimyristyl trithiophosphite, tristearyl trithiophosphite, and triphenyl trithiophosphite.

In particular, phosphites or thiophosphites represented by the formula P(XR)3 are preferably used, and thiophosphites represented by the formula P(SR)3 are more preferably used. Two or more of these phosphorus compounds may be used in combination.

The amounts of the copper compound and phosphorus compound used in the present invention are not particularly limited, but are each 10 ppm to 5% by weight based on the theoretical amount of the reaction product.

Preferably they are each 100 to 5000 ppm.

In the method of the present invention, the organic copper compound and P (X
R) It is preferable to use phosphites or thiophosphites represented by the formula 3 in combination.

A catalyst may be used in the method of the present invention if necessary. Catalysts include inorganic acids such as sulfuric acid and sulfurous acid; organic acids such as methanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid; organic bases such as triethylamine, pyridine, dimethylaniline, and sodium acetate; and acidic ion exchange resins.

Examples include, but are not limited to, basic ion exchange resins. The amount of these catalysts used is not particularly limited, but is usually used in an amount of 10% by weight or less of the theoretical product amount.

According to the method of the invention, N-substituted maleimides are.

For example, it is prepared as follows. First, maleic anhydride and at least one of the copper compounds are added to the organic solvent.
A seed, at least one of the above phosphorus compounds, and if necessary the above catalyst are added and dissolved by heating. The liquid temperature is generally raised to 50 to 200°C, preferably 70 to 130°C, and the primary amine is gradually added while the solvent is refluxed, and the reaction is carried out at the same temperature for 2 to 5 hours. At this time, water that is azeotropic with the solvent is removed from the reaction system.

In this way, a transparent reaction solution containing N-substituted maleimides is obtained. 1. Wash this using the usual method,
Thereafter, the solvent is distilled off, and if necessary, the product is separated and purified by further distillation, recrystallization, etc., to obtain a pure N-substituted maleimide.

According to the method of the present invention, the reaction solution does not become colored during one reaction, and furthermore, side reactions such as the formation of polymeric by-products due to the polymerization of N-substituted maleimides do not occur, so the solvent can be distilled off. At the step of removal, highly pure N-substituted maleimides with no coloration are obtained, and purification steps such as distillation and recrystallization are not necessarily required. Therefore, according to the present invention, the labor required for the two separation and purification steps can be greatly reduced.

(Examples) The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto.

Maleic anhydride 103
g (I, 05 mol), toluene 400 g, dimethylformamide 20 g, p-toluenesulfonic acid 5
g.

Then, 0.17 g of copper acetate and 0.17 g of triphenyltrithiophosphite, each having an amount of 11,000 pp based on the theoretical amount of the reaction product, were charged and dissolved by heating under stirring.

The mixture was then heated to 115°C and the solvent was refluxed. Into this, aniline 93. tg (I, 0 mol)
was added dropwise from the dropping funnel over a period of 2 hours. Thereafter, this mixture was kept at the same temperature and allowed to age for 0.5 hour.

During this reaction, the water produced was removed from the water separator.

The reaction solution obtained after the reaction was a bright pale yellow transparent liquid. As a result of analysis by gel permeation chromatography (GPC), no formation of bulky by-products was observed, and the formation of 172.0go)N phenylmaleimide was confirmed (yield 994%).

Then, the reaction solution was cooled to 60'C, and 10
After neutralization by adding % sodium carbonate aqueous solution, washing and liquid separation operations were repeated twice at the same temperature using an amount of water equal to one reaction solution. The solvent was then distilled off under reduced pressure (final bath i: 110'C.

Final degree of vacuum reached: 1 mmHg), and 170.5 g of N-phenylmaleimide was obtained (yield: 298.6%).

The N-phenylmaleimide thus obtained is 8
It is a pale yellow solid with a melting point of 9-90°C.

As a result of GPC analysis, the purity was 99.9%.

Next, in order to confirm that a distillation or recrystallization step is not necessarily necessary in the manufacturing process, the above N-phenylmaleimide was distilled under reduced pressure. As a result, no distillation residue was observed, and the distilled N-phenylmaleimide had one hue.
It was confirmed that the quality, including appearance, was almost the same as that of undistilled product. The analysis results are shown in Example 2 below.
3 and the results of Comparative Examples 1 to 4 are shown in the table.

In place of copper acetate and triphenyltrithiophosphite, 0.34 g of p-methoxyphenol (2000+ based on the theoretical reaction product amount), a common polymerization inhibitor, was used.
) Ill) The reaction was carried out in the same manner as in Example 1, except that 1) was used. As a result, a slurry-like, yellow-brown, opaque reaction solution containing a large amount of insoluble by-products was obtained.

As a result of analysis by GPC, the amount of N-phenylmaleimide produced was 155.5 g (reaction yield: 89.9%), and the reaction solution contained about 5% of polymeric by-products. In addition, the presence of numerous other by-products was confirmed.

Then, after filtering off the slurry-like insoluble by-products,
The reaction solution was washed and separated for 143 minutes in the same manner as in Example 1.
Obtained 0 g of a tan solid. N obtained as a result of GPC analysis
- The purity of phenylmaleimide was 95.1%.
This N-phenylmaleimide was then distilled under reduced pressure to obtain 129.5 g of pure N-phenylmaleimide (yield: 74.8%). A large amount of polymerized blackish brown tar-like substance was observed in the distillation residue.

0.34 g of copper sulfate (20 g based on the theoretical amount of reaction product) in place of copper acetate and triphenyltrithiophosphite
The reaction was carried out in the same manner as in Example 1 except that 00 ppm) was used. As a result, a slightly opaque reddish-brown reaction solution was obtained.

As a result of analysis by GPC, the amount of N-phenylmaleimide produced was 159.5 g (reaction yield 97.9%).

Next, the same operation as in Example 1 was performed to distill off the solvent,
165.5 g of a reddish-brown solid was obtained. As a result of GPC analysis, the purity of the obtained N-phenylmaleimide was 985%.
The 1 reaction contained small amounts of polymeric side reactants. This N-phenylmaleimide was then distilled under reduced pressure to obtain 157.0 g of pure N-phenylmaleimide (yield: 907%). A small amount of polymerized blackish brown tar-like substance was observed in the distillation residue.

The reaction was carried out in the same manner as in Example 1, except that 107.2 g of o-toluidine was used instead of the main aniline.

Subsequently, the solvent was distilled off.

As in Example 1, a reaction product with external U and quality equivalent to that of the distilled product was obtained.

ratio! Hindered phenol, i.e. 2,4-bis(II-octylthio)-6-(4-hydroxy-3,5-di-safetylanilino)-, instead of copper acetate and triphenyltrithiophosphite 1,3,5-) riazine 0.34
The reaction was carried out in the same manner as in Example 2, except that 2000 ppm of the reaction product was used.

As a result, a yellow-brown opaque reaction solution containing a slurry-like insoluble side reaction product was obtained. Next, purification was performed in the same manner as in Comparative Example 1.

The reaction was carried out in the same manner as in Example 1, except that 127.6 g of O-chloroaniline and 7 g of triphenylphosphite O,i were used in place of aniline and triphenyltrithiophosphite, and then the solvent was removed.

In this case, as in Example 1, a reaction product with the same appearance and quality as the distilled product was obtained.

Contains Δ5 industrial vinegar Mj [i and triphenyl phosphite, and 4 g of copper acetate QJ (2000 pp based on the theoretical amount of reaction product)
The reaction was carried out in the same manner as in Example 3 except that m) was used,
Subsequently, the solvent was distilled off.

As a result, a reddish brown solid containing a small amount of polymeric side reaction product was obtained. Next, by the same operation as in Comparative Example 1,
Refined.

(Effects of the Invention) As described above, according to the method of the present invention, side reactions are effectively suppressed in the reaction between maleic anhydride and primary amines, and high-purity N that is not colored brown is produced. -Substituted maleimides can be produced in high yields. Then, the obtained N-
Since the purity of the substituted maleimide is sufficiently high, the purification process can be simplified and the N-substituted maleimide can be produced at low cost.

that's all

Claims (1)

[Claims] 1. A method for producing N-substituted maleimides using maleic anhydride and an aromatic or aliphatic primary amine as raw materials, the method comprising: maleic anhydride and the primary amine; In the coexistence of a copper compound and at least one phosphorous compound in an organic solvent capable of azeotropic distillation with water, the produced water is azeotroped with the organic solvent and discharged from the reaction system, while heating at 50 to 200°C. A method for producing N-substituted maleimides, which includes the step of performing an imidization reaction at a temperature to obtain N-substituted maleimides. 2. The method according to claim 1, wherein the primary amine is an aromatic primary amine. 3. The method according to claim 1, wherein the copper compound is an organic copper compound. 4. The method according to claim 1, wherein the phosphorus compound is selected from the group of compounds represented by the following formula (I): P(XR)_3(I) where X is independently an oxygen atom or It is a sulfur atom, and R is H or an aliphatic or aromatic hydrocarbon group of C_1 to C_1_8. 5. The method according to claim 4, wherein the phosphorus compound is selected from the group of compounds represented by the following formula (II): P(SR)_3(II), where R is independently H or C_1 ~C_1_8 is an aliphatic or aromatic hydrocarbon group.