JPS6058752B2 - Method for producing N-(4-fluorophenyl)-2,3-dichloromaleimide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing N-(4-fluorophenyl)-2,3-dichloromaleimide.

More specifically, it is an object of the present invention to provide a method for producing the above-mentioned compound having excellent bactericidal activity with high purity and industrially advantageously. Recently, there has been a demand for safer pesticides in terms of persistence, toxicity, etc.
It is becoming necessary to confirm the safety of not only the main ingredients but also the impurities contained in large quantities. From this point of view, it is meaningful to produce highly pure agricultural chemical ingredients. We first reacted 2,3-dichloromaleic acid or its anhydride with 4-fluoroaniline in an organic solvent, or reacted them in an aqueous medium to form N-
-fluorophenyl)-2,3-dichloromaleimide (Japanese Patent Publication No. 47-20012, Japanese Patent Application Publication No. 49-110661, Japanese Patent Application Publication No. 50-148354),
As a result of further studies on a method for industrially advantageous production of this compound with high purity, we found that 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline were mixed in water in the presence of an appropriate amount of a strong acidic substance. When these compounds are reacted in an organic solvent, N-(4-fluorophenyl)-2|3- can be produced in higher yield and purity than when reacting in an organic solvent.
Known that dichloromaleimide can be obtained, and also the characteristics when these compounds are reacted in a simple aqueous medium, such as the ability to obtain a product with a uniform particle size that is easy to handle in high yield. The inventors have found that N-(4-fluorophenyl)-2,3-dichloromaleimide of higher purity can be stably obtained without damaging the product, and have arrived at the present invention.

In the conventional imide production reaction, aromatic hydrocarbons such as benzene, toluene, and xylene, chlorinated alkanes such as chloroform and carbon tetrachloride, ketones such as acetone and methyl ethyl ketone, lower alcohols such as methanol and ethanol, Although it is common to use organic solvents such as fatty acids such as acetic acid, N-
In the production of (4-fluorophenyl)-2,3-dichloromaleimide, an improved method has been discovered in which the reaction is carried out in an aqueous medium, and the characteristics of this method are high yield and fine particles. The goal is to obtain uniform particles.

The present inventors investigated in more detail this improved method of carrying out the reaction in an aqueous medium, and found that although the yield was very good, the by-product N-(4-fluorophenyl)-2 was present in the product. -(4-fluorophenylamino)-3-
Several percent of chloromaleimide is mixed in, and the amount of by-product can be reduced to 0 depending on subtle differences in reaction conditions, such as dropping method, stirring state, etc.
．． It was recognized that it was difficult to control the amount of by-products so that they were always small, as they fluctuated between 5 and 5%. Also, p
- Even when the reaction is carried out in an aromatic hydrocarbon such as benzene using a catalyst such as toluenesulfonic acid, 2 to 5
It was confirmed that % of N-(4-fluorophenyl)-2-(4-fluorophenylamino)-3-chloromaleimide was mixed into the product.

As a result of intensive studies by the present inventors to improve these drawbacks, we found that 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline were reacted with water and/or in the presence of hydrochloric acid and/or -sulfuric acid. If the product is separated and reacted in an aqueous medium consisting of the Oki liquid obtained, N-(4-fluorophenyl)-2,3-dichloromaleimide can be produced in high yield and purity, and is easy to handle. Fine, uniform particles can be easily obtained. The present invention was completed in recognition of this.

Next, to explain the present invention in detail, 2,3-dichloromaleic acid or its anhydride, which is a raw material for the method of the present invention, can be produced by various methods.

For example, dichloromaleic acid is 3-formin-2,3
It is obtained by oxidizing -dichloroacrylic acid with fuming nitric acid (Ber.?, 2588-90). In addition, dichloromaleic anhydride can be obtained by reacting maleic anhydride with chlorine in the presence of iron (USSR Patent No. 4341
Has). The method of the present invention is carried out in the presence of hydrochloric acid, sulfuric acid or a mixture thereof. The concentration of the hydrochloric acid or sulfuric acid aqueous solution used is 0.1N~△
is used.

If the concentration is lower than this, N-(4-fluorophenyl)-
This is not preferred because the amount of by-product 2-(4-fluorophenylamino)-3-chloromaleimide increases and it becomes difficult to control the amount of by-product. Moreover, if the concentration becomes higher than this, the yield will decrease, which is not preferable. The amount of hydrochloric acid or sulfuric acid aqueous solution used is preferably 5 to 2 times the amount of 4-fluoroaniline.

If the amount used is less than this, the slurry concentration of the reaction solution will become too high, making handling extremely difficult. Moreover, if it is more than this, the space-time yield becomes poor, which is not preferable. When carrying out the reaction, it is sufficient that the concentration and amount of hydrochloric acid or sulfuric acid and water after mixing are within the above range, and the reaction can be carried out, for example, in the following combinations. (1) 2,3-dichloromaleic acid or its anhydride in an aqueous solution of hydrochloric acid or sulfuric acid and 4
- Fluoroaniline (Ii) in an aqueous solution of 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline (Iii) in an aqueous solution of hydrochloric acid or sulfuric acid; 2,3-dichloromaleic acid or its anhydride in an aqueous solution of hydrochloric acid or sulfuric acid; When reacting 2,3-dichloromaleic acid or its anhydride with 4-fluoroaniline and 4-fluoroaniline in an aqueous solution of hydrochloric acid or sulfuric acid, dichloromaleic acid or its anhydride reacts with 4-fluoroaniline. Usually 0.8
It is used in a mole to 2 times the mole, preferably 0.9 to 1.3 times the mole.

In addition, the reaction temperature is usually 30 to 150°C, preferably 40°C.
, to reflux temperature. In addition, in this reaction, 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline are mixed dropwise in the presence of hydrochloric acid or sulfuric acid, and then the reaction is completed. If this is the second step, the first step can be carried out at a temperature below 70°C, and the second step can be carried out at a temperature of 700°C to reflux. The method of dropping 4-fluoroaniline into 2,3-dichloromaleic acid or its anhydride is preferred, but when the reaction is carried out in two steps as described above, the reverse dropping method also yields high yields. The target compound can be obtained with high purity.

The reaction time is not particularly limited and can be selected from a wide range, but the reaction is usually completed within 1 to 10 minutes.

When carrying out a two-stage reaction, the first stage is a reaction immediately after dropping, so the reaction time can be 1 to 6 times as long as the dropping time is taken.
The second stage is 1-20 hours.

After the reaction is cooled, highly pure N-(4-fluorophenyl)-2,3-dichloromaleimide can be obtained in a high yield simply by filtering the precipitated crystals. Further, water alone can be used as the aqueous medium used in the reaction, but it is also possible to use the reaction solution as it is in the next reaction, and it is more effective to recycle the solution.

In other words, since the reaction is extremely selective according to the method of the present invention, among the 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline used, the target product N-(4-fluoroaniline Most of the portion that did not become N-(4-fluorophenyl)-2,3-dichloromaleimide was recovered in the Oki liquid as unreacted and/or reaction intermediates, and if this was recycled, it was converted into N-(4-fluorophenyl). )-2
, 3-dichloromaleimide, and completely equivalent quality products can be obtained. This means that not only the basic unit of raw materials and auxiliary agents used is reduced, but also the amount of wastewater is reduced, which is extremely advantageous industrially as it reduces the burden of wastewater treatment. As explained above, according to the method of the present invention, as shown in the following examples, it can be used as an agricultural fungicide, especially for anthracnose disease of cucumber, citrus black spot, tomato late blight, rice blast disease, apple spot leaf spot disease, and scabrous blight. N-(4-fluorophenyl)-2,3-dichloromaleimide, which has excellent effects such as the following, can be obtained in high yield, with high purity, and with industrial advantage.

Next, the method of the present invention will be explained in more detail with examples.
The present invention is not limited to the following examples unless it exceeds the gist thereof. In addition, the melting point described in the example is M
The melting point of N-(4-fluorophenyl)-2,3-dichloromaleimide, which has been recrystallized with acetone and purified by sublimation, is 240.3 to 241.9°, which is a value measured with an Ettler FP-51 type melting point analyzer. It was C.

Furthermore, in the examples, the term "yield" simply means the yield relative to 4-fluoroaniline. Example 1 2,3-dichloromaleic anhydride 80.14y(a).
48rr101) was dissolved in 565ml of 0.354N hydrochloric acid, and 44.45y of 4-fluoroaniline was dissolved at 60°C with stirring.
(stomach). After dropping 1 powder of 4m01), the temperature was raised to 90°C,
Thereafter, the reaction is allowed to proceed for 4 hours.

After cooling, it is separated, thoroughly washed with water, and dried to obtain an average particle size of 12.8.
μ, N-(4-fluorophenyl)-2,3-dichloromaleimide 99.74, melting point 239.6-240.9°C
9 was obtained (yield 95.9%). As a result of gas chromatography, N-(4-fluorophenyl)-2-(4-fluorophenylamino)-3-chloromaleimide was 0.22W.
t% of by-products were produced, and no other by-products were observed. Example 2 In the same manner as in Example 1 except that sulfuric acid was used instead of hydrochloric acid, 100. 8
6y was obtained (yield 97.0%).

The amount of by-product of N-(4-fluorophenyl)-2-(4-fluorophenylamino)-3-chloromaleimide is 0.
．． It was 15 wt%. Example 3 40.07 g of 2,3-dichloromaleic anhydride (a).
24m01) in 277ml of 1.442N hydrochloric acid,
22.22y of 4-fluoroaniline (
4). 2n101) was added dropwise in one drop, and then reacted for 8 hours.

After cooling, separate, thoroughly wash with water and dry to obtain a melting point of 239.9~
241.4, C(7)N-(4-fluorophenyl)-
46.78y of 2,3-dichloromaleimide was obtained (yield 89.9%). N-(4-fluorophenyl)-2-(
No by-product of 4-fluorophenylamino)-3-chloromaleimide was observed (gas chromatography detection limit 0.01
Wt%). Example 4 Obtained in Example 3! Door liquid 270.6y 1.442N
19mt of hydrochloric acid was added, 34.65y (0.2075m01) of 2,3-dichloromaleic anhydride was dissolved therein, and 4-fluoroaniline (4). 2n
101) was added dropwise into the solution, and the mixture was allowed to react for 8 hours.

After cooling, it is separated, thoroughly washed with water and dried to obtain a melting point of 240.1~
N-(4-fluorophenyl)-2,3 at 241.2°C
-49.75y of dichronoromaleimide was obtained (yield: 95
．． 7%). N-(4-fluorophenyl)-2-(4-
No by-product of fluorophenylamino-3-chloromaleimide was observed. If the liquid is collected in this way and used for the next reaction, the yield will be improved.

This indicates that the portion of the initially used raw materials that did not become the target product was recovered in the liquid as unreacted or/and reaction intermediates, indicating that the reaction was extremely selective. do. Example 5 2,3-dichloromaleic anhydride 31.72y(4).
19rn01) in 274ml of 0.365N hydrochloric acid, and stirred at 60'C to dissolve 22.22y of 4-fluoroaniline.
(0.20TT101) was added dropwise in one drop, the temperature was raised to 90°C, and the mixture was allowed to react for 4 hours.

Claims (1)

[Claims] 1. From the filtrate obtained by separating the reaction product of 2,3-dichloromaleic acid or its anhydride and 4-fluoroaniline with water and/or in the presence of hydrochloric acid and/or sulfuric acid. A method for producing N-(4-fluorophenyl)-2,3-dichloromaleimide, which is characterized by carrying out the reaction in an aqueous medium. 2. The manufacturing method according to claim 1, wherein the concentration of hydrochloric acid and/or sulfuric acid is 0.1 to 2 normal. 3. The manufacturing method according to claim 1 or 2, characterized in that 2,3-dichloromaleic acid or its anhydride is used in an amount of 0.8 to 2 times the mole of 4-fluoroaniline.