JPS645594B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is a novel compound, N-substituted aminomaleimide, and a method for producing the same. More specifically, the invention provides the formula [In the formula, R ¹ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, m is 0, 1, 2, or 3, and R ² represents an alkyl group having 1 to 4 carbon atoms, or a halogen atom; 4 alkyl group, benzyl group, cyclohexyl group, or

[Formula] (R ³ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, and n is 0, 1,
2 or 3. ), X ¹
represents an alkoxycarbonyl group having 2 to 5 carbon atoms, a fatty acid acyl group having 2 to 5 carbon atoms, a benzoyl group, or a cyano group. ], and N-substituted aminomaleimides of the formula (In the formula, R ¹ , m and X ¹ each have the same meaning as above.) Aminomaleimide represented by the formula R ² −N=C=O ^[ ] An N-substituted aminomaleimide represented by the formula [], characterized in that an isocyanate represented by the formula (having the same meaning as above) is reacted in the presence of a tertiary amine and a mono- or quaternary ammonium fluoride. This is a similar manufacturing method. N-substituted aminomaleimides represented by the formula [] are new compounds and are useful as medicines, agricultural chemicals, and intermediates thereof. It is particularly useful as an agricultural and horticultural fungicide against rice blight and cucumber powdery mildew. In this invention, the reaction of aminomaleimide represented by formula [] with isocyanate represented by formula [] in the presence of a tertiary amine and/or quaternary ammonium fluoride base is shown by the following formula. It is thought that the process proceeds through the formation of carbamoylaminomaleimide represented by the formula [] as an intermediate. Specific examples of aminomaleimides represented by the formula [] include 3-amino-4-ethoxycarbonyl-1-phenylmaleimide, 3-amino-4
-ethoxycarbonyl-1-tolylmaleimide,
3-amino-1-chlorophenyl-4-ethoxycarbonylmaleimide, 3-amino-1-dichlorophenyl-4-ethoxycarbonylmaleimide, 3-acetyl-4-amino-1-phenylmaleimide, 3-acetyl-4- Amino-1-methoxyphenylmaleimide, 3-acetyl-4-amino-1-xylylmaleimide, 3-acetyl-
4-amino-1-dichlorophenylmaleimide,
3-amino-4-benzoyl-1-phenylmaleimide, 3-amino-4-benzoyl-1-tolylmaleimide, 3-amino-4-benzoyl-1
-chlorophenylmaleimide, 3-amino-4-
benzoyl-1-dichlorophenylmaleimide,
3-amino-4-cyano-1-phenylmaleimide, 3-amino-4-cyano-1-tolylmaleimide, 3-amino-4-cyano-1-dichlorophenylmaleimide, 3-amino-1-phenyl-
4-propionylmaleimide, 3-amino-4-
Examples include butyryl-1-phenylmaleimide, 3-amino-1-phenyl-4-valerylmaleimide, and the like. Specific examples of the isocyanate represented by the formula [] include methyl isocyanate, ethyl isocyanate, propyl isocyanate, butyl isocyanate, benzyl isocyanate, cyclohexylyisocyanate, phenyl isocyanate, tolyl isocyanate, and methoxyl isocyanate. enyl isocyanate, chlorophenyl isocyanate,
Examples include dichlorophenyl isocyanate. Specific examples of the tertiary amine include aliphatic tertiary amines such as trimethylamine, triethylamine, tripropylamine, and tributylamine. Quaternary ammonium fluoride has the formula (In the formula, R ⁴ , R ⁵ , R ⁶ and R ⁷ each represent an alkyl group or a benzyl group having 1 to 4 carbon atoms.)
It is a compound represented by, and specific examples thereof include benzyltrimethylammonium fluoride,
Examples include methyltributylammonium fluoride, tetraethylammonium fluoride, tetrabutylammonium fluoride, and tetramethylammonium fluoride. The reaction is carried out in the presence of an inert organic solvent, such as an aromatic hydrocarbon such as benzene, toluene, chlorobenzene, dichlorobenzene, or a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride, ethylene chloride. As a reaction method, under substantially anhydrous conditions,
Any method for contacting the aminomaleimide, isocyanate, and tertiary amine and/or quaternary ammonium fluoride can be employed, and there are no particular restrictions on the order of their addition. The amount of isocyanate used is 1 to 2 moles per mole of aminomaleimides. The amounts of tertiary amine and quaternary ammonium fluoride used are preferably 1 to 3 mol and 0.1 to 1 mol, respectively, per 1 mol of aminomaleimide. In this reaction, a tertiary amine and a quaternary amine
Ammonium fluoride promotes the reaction between aminomaleimide and isocyanate and the decomposition reaction of the resulting intermediate carbamoylaminomaleimide to N-substituted aminomaleimide. When aromatic isocyanates are used, tertiary amine and quaternary ammonium fluoride are usually used alone, but when using aliphatic isocyanates with low reactivity, they are used to speed up the reaction. , 3rd
Preferably, a combination of amine and quaternary ammonium fluoride is used. The reaction is generally carried out at a temperature ranging from 20 to 150°C.
It lasts from 1 to 50 hours. Since the target product, the N-substituted aminomaleimide represented by the formula [], is a crystal, it can be isolated from the reaction product mixture by utilizing the difference in solubility. Specific examples of carbamoylaminomaleimides represented by the formula [] of this invention include 3-anilino-4-ethoxycarbonyl-1-phenylmaleimide, 3-chloroanilino-4-ethoxycarbonyl-1-phenylmaleimide, 3-chloroanilino-4-ethoxycarbonyl-1-phenylmaleimide, -cyclohexylamino-4-ethoxycarbonyl-1-
Phenylmaleimide, 3-cyclohexylamino-4-ethoxycarbonyl-1-dichlorophenylmaleimide, 3-ethoxycarbonyl-4-methoxyanilino-1-tolylmaleimide, 3-benzylamino-4-ethoxycarbonyl-1-tolyl Maleimide, 1-chlorophenyl-3-ethoxycarbonyl-4-toluidinomaleimide, 3
-anilino-1-dichlorophenyl-4-(ethoxycarbonyl)maleimide, 1-dichlorophenyl-3-ethoxycarbonyl-4-(trifluoromethyl)anilinomaleimide, 3-anilino-4-benzoyl-1-phenyl enylmaleimide, 3
-Benzoyl-1-chlorophenyl-4-toluidinomaleimide, 3-anilino-4-benzoyl-1-dichlorophenylmaleimide, 3-benzoyl-1-dichlorophenyl-4-ethylaminomaleimide, 3-acetyl-4 -Anilino-1-
Phenylmaleimide, 3-acetyl-1-phenyl-4-toluidinomaleimide, 3-acetyl-
4-isopropylamino-1-methoxyphenylmaleimide, 3-acetyl-4-dichloroanilino-1-xylylmaleimide, 3-acetyl-4
-Butylamino-1-dichlorophenylmaleimide, 3-chloroanilino-4-cyano-1-phenylmaleimide, 3-anilino-4-cyano-1
-Tolylmaleimide, 3-cyano-1-dichlorophenyl-4-methylaminomaleimide, 3-anilino-1-phenyl-4-propionylmaleimide, 3-anilino-4-butyryl-1-phenylmaleimide, 3-anilino -1-phenyl-4
-valeryl aleimide and the like. Next, examples will be shown. In the examples, the yield of N-substituted aminomaleimide is the yield based on the aminomaleimide used. Example 1 3-Amino-
Add 1.30 g of 4-ethoxycarbonyl-1-phenylmaleimide, then add phenyl isocyanate.
5 ml of ethylene chloride containing 1.19 g was added dropwise. The mixture was heated and reacted under reflux for 2 hours. After the reaction, the resulting reaction mixture was filtered to obtain 0.15 g of cyanuric acid crystals. The liquid was concentrated under reduced pressure, 5 ml of ethanol was added to the residue, filtered, and 3-
1.47 g (87%) of crystals of anilino-4-ethoxycarbonyl-1-phenylmaleimide were obtained. This was recrystallized from ethanol to obtain yellow needle crystals with a melting point of 182-184°C. The elemental analysis values are shown below. C H N Analytical value 67.84 4.86 8.30 Calculated value 67.85 4.79 8.33 (as C ₁₉ B ₁₆ N ₂ O ₄ ) Example 2 0.51 g of triethylamine and 1.30 g of 3-amino-4-ethoxycarbonyl-1-phenylmaleimide
When 5 ml of ethylene chloride containing 1.19 g of phenyl isocyanate was added dropwise at room temperature to 25 ml of ethylene chloride containing g, the temperature of the mixture rose from 24°C to 28°C and the mixture became a yellow-brown solution. The mixture was allowed to react for 1 day with stirring at room temperature. After the reaction, the resulting reaction mixture was filtered to obtain 0.05 g of cyanuric acid crystals. The liquid was concentrated under reduced pressure, 5 ml of ethanol was added to the residue, filtered, and 3-
1.32 g (78%) of crystals of anilino-4-ethoxycarbonyl-1-phenylmaleimide were obtained. Example 3 Ethylene chloride 45 containing 5 mmol of tetraethylammonium fluoride and 0.51 g of triethylamine
ml, add 1.37 g of 3-amino-4-ethoxycarbonyl-1-(p-tolyl)maleimide at room temperature,
Then, 10 ml of ethylene chloride containing 1.32 g of benzyl isocyanate was added dropwise. The mixture was allowed to react for 5 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure. Add 30ml of water to the residue and dilute with 50ml of benzene.
Extracted once and twice with 20 ml. Combine the extracts and
After drying over anhydrous sodium sulfate, it was concentrated under reduced pressure. Add 10 ml of ethanol to the residue and filter.
3-Benzylamino-4-ethoxycarbonyl-
1.27g crystals of 1-(p-tolyl)maleimide (70
%) was obtained. This was recrystallized from isopropyl alcohol to obtain yellow prismatic crystals with a melting point of 153-154°C. The elemental analysis values are shown below. C H N Analyzed value 68.85 5.56 7.79 Calculated value 69.22 5.53 7.69 (as C ₂₁ H ₂₀ N ₂ O ₄ ) Example 4 Ethylene chloride containing 5.3 mmol of tetraethylammonium fluoride and 0.51 g of triethylamine
To 30 ml was added 1.65 g of 3-amino-1-(2,4-dichlorophenyl)-4-ethoxycarbonylmaleimide at room temperature, followed by dropwise addition of 50 ml of ethylene chloride containing 1.25 g of cyclohexyl isocyanate. The mixture was heated and reacted under reflux for 2 hours. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure. 50 ml of benzene and 30 ml of water were added to the residue, and the layers were separated into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. Add 10 ml of ethanol to the residue and filter it to give 3-cyclohexylamino-1-(2,4-dichlorophenyl)-
Crystals of 4-(ethoxycarbonyl)maleimide
1.32g (64%) was obtained. This was recrystallized with ethanol to obtain yellow needle crystals with a decomposition point of 314°C. The elemental analysis values are shown below. C H N Cl Analytical value 55.61 4.76 6.62 16.92 Calculated value 55.49 4.90 6.81 17.24 (as C ₁₉ H ₂₀ Cl ₂ N ₂ O ₄ ) Example 5 Ethylene chloride 25 containing 0.51 g of triethylamine
ml of 3-amino-4-benzoyl-1- at room temperature.
Add 1.46 g of phenylmaleimide, then 25 ml of ethylene chloride containing 1.19 g of phenyl isocyanate.
was added dropwise. The mixture was allowed to react for 2 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture is filtered,
0.04 g of cyanuric acid crystals were obtained. Concentrate the liquid under reduced pressure, add 10 ml of ethanol to the residue, filter it,
1.38 g (75%) of crystals of 3-anilino-4-benzoyl-1-phenylmaleimide were obtained. This was recrystallized from ethanol to obtain yellow needle crystals with a melting point of 221-222°C. The elemental analysis values are shown below. C H N Analyzed value 75.21 4.51 7.53 Calculated value 74.99 4.38 7.60 (as C ₂₃ H ₁₆ N ₂ O ₃ ) Example 6 Ethylene chloride 30 containing 5 mmol of tetraethylammonium fluoride and 0.51 g of triethylamine
ml of 3-amino-4-benzoyl-1- at room temperature.
(3,5-dichlorophenyl)maleimide 1.81g
was then added dropwise to 10 ml of ethylene chloride containing 0.79 g of ethyl isocyanate. The mixture was heated and reacted under reflux for 1 hour. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure. Add 20ml of benzene to the residue and filter.
The liquid was passed through a column (diameter 25 mm) packed with silica gel (Wako Gel C-200, 100 g) and eluted with a mixed solvent of benzene and ethyl acetate in a volume ratio of 9:1.
After elution with 150 ml of solvent, the solution obtained by elution with 400 ml of solvent was concentrated under reduced pressure to obtain 3-benzoyl-
0.44 g (23%) of crystals of 1-(3,5-dichlorophenyl)-4-ethylaminomaleimide was obtained. This was recrystallized from ethanol to obtain yellow needle crystals with a melting point of 214°C. The elemental analysis values are shown below. C H N Analytical value 58.39 3.63 6.83 Calculated value 58.63 3.63 7.20 (as C ₁₉ H ₁₄ Cl ₂ N ₂ O ₃ ) Example 7 Ethylene chloride 25 containing 0.51 g of triethylamine
ml at room temperature, and then 5 ml of ethylene chloride containing 1.19 g of phenyl isocyanate were added dropwise. While stirring the mixture at room temperature,
The reaction was allowed to proceed for 1 hour. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure to obtain 2.50 g of black-brown crystals. Add 10 ml of ethanol to this, filter it, and crystallize 0.95 g of 3-acetyl-4-anilino-1-phenylmaleimide.
(62%). This was recrystallized with ethanol,
Orange petal-shaped crystals with a melting point of 201-202°C were obtained. The elemental analysis values are shown below. C H N Analytical value 70.63 4.68 9.15 Calculated value 70.58 4.61 9.15 (as C ₁₈ H ₁₄ N ₂ O ₃ ) Example 8 Ethylene chloride 25 containing 0.51 g of triethylamine
1.15 g of 3-acetyl-4-amino-1-phenylmaleimide was added to the solution at room temperature, and then a solution obtained by dissolving 1.33 g of p-tolylisocyanate in 5 ml of ethylene chloride was added dropwise. The mixture was allowed to react for 17 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure. Add 5 ml of ethanol to the residue and filter it.
0.41 g (26%) of crystals of 3-acetyl-1-phenyl-4-(p-toluidino)maleimide was obtained.
This is recrystallized from ethanol and has a melting point of 194-195℃.
crystals were obtained. The elemental analysis values are shown below. C H N Analyzed value 71.42 5.12 8.73 Calculated value 71.24 5.03 8.74 (as C ₁₉ H ₁₆ N ₂ O ₃ ) Example 9 Ethylene chloride containing 1.7 mmol of tetraethylammonium fluoride and 0.51 g of triethylamine
Add 3-acetyl-4-amino-1- to 30 ml at room temperature.
Add 13g of (p-methoxyphenyl)maleimide,
Then 20 ml of ethylene chloride containing 0.85 g of isopropyl isocyanate was added dropwise. The mixture was heated and reacted under reflux for 2 hours. After the reaction, the resulting reaction product mixture was concentrated under reduced pressure. 50 ml of benzene, 30 ml of water and 1 activated carbon in the residue
g was added and filtered, and the liquid was separated into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was transferred to a column (diameter
25 mm) and eluted with a mixed solvent of benzene and ethyl acetate in a volume ratio of 9:1. After elution with 400 ml of solvent, the solution obtained by elution with 500 ml of solvent was concentrated under reduced pressure to obtain 0.35 g (23 %) was obtained. This was recrystallized with 20 ml of ethanol to obtain yellow petal-shaped crystals with a melting point of 135-135.5°C. The elemental analysis values are shown below. C H N Analyzed value 63.48 6.01 8.89 Calculated value 63.57 6.00 9.27 (as C ₁₆ H ₁₈ N ₂ O ₄ ) Example 10 Ethylene chloride 50 containing 0.51 g of triethylamine
ml of 3-acetyl-4-amino-1- at room temperature.
Add 1.29 g of (2,5-xylyl)maleimide,
Then 3,5-dichlorophenyl isocyanate
Added 1.88g. While stirring the mixture at room temperature,
The reaction was allowed to proceed for 2 hours. After the reaction, the resulting reaction mixture was filtered, the liquid was concentrated under reduced pressure, and the residue was filtered by adding 30 ml of ethylene chloride to give 3-acetyl-4-(3,5-dichloroanilino)-1-( 0.72 g (36%) of crystals of 2,5-xylyl)maleimide were obtained. This was recrystallized from ethanol to obtain yellow needle crystals with a melting point of 218-219°C. The elemental analysis values are shown below. C H N Analytical value 59.58 3.95 6.75 Calculated value 59.57 4.00 6.95 (as C ₂₀ H ₁₆ Cl ₂ N ₂ O ₃ ) Example 11 Ethylene chloride 30 containing 0.51 g of triethylamine
1.06 g of 3-amino-4-cyano-1-phenylmaleimide was added at room temperature, followed by dropwise addition of 20 ml of ethylene chloride containing 1.54 g of p-chlorophenyl isocyanate. The mixture was allowed to react for 20 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was filtered.
The liquid was concentrated under reduced pressure, and 20 ml of benzene was added to the residue and filtered to give 1.43 g (89
%) was obtained. This was recrystallized from acetonitrile to obtain yellow needle crystals with a melting point of 280-282°C. The elemental analysis values are shown below. C H N Analytical value 63.17 3.08 12.49 Calculated value 63.07 3.11 12.98 (as C ₁₇ H ₁₀ ClN ₃ O ₂ ) Reference example 1 Control test against rice leaf blight (water surface application) (1) Preparation of wettable powder for test. A wettable powder is made by mixing and pulverizing 20 parts of the supply agent, 1 part of Demol, 20 parts of white carbon, and 59 parts of talc.
Got 100 copies. (2) Prevention test. Paddy rice (variety: Nipponbare) was sown at 5 grains each in synthetic resin cultivation pots with a diameter of 6 cm, and then grown in a glass greenhouse, and the rice at the 5.5 to 6.6 leaf stage was used for testing. 3 ml of the hydrating agent prepared in the above method was diluted with water to make the concentration of the test drug 500 ppm.
Water surface treatment was applied. After application, the plants were left in a glass greenhouse for two days to allow the chemicals to be fully absorbed from underground, and then inoculated. The inoculum was prepared by culturing Xanthomonas oryzeae at 28℃ for 48 hours with shaking in Suwa liquid medium, then
The number of bacteria was adjusted to 10 ^{7 to} 8, and inoculation was performed by two-needle inoculation onto the leaf blades of the upper two leaves, avoiding the main vein. After inoculation, the plants were kept in a glass greenhouse, and two weeks after inoculation, the number of rice seedlings (n ₁ to n ₇ ) with each severity of rice leaf blight was investigated according to the following evaluation criteria. The number of test plants in each area was 30. Evaluation criteria for severity of disease 0: No disease observed at all (number of rice seedlings; n ₁ ) 1: Very slight disease onset (number of rice seedlings;
n ₂ ) 2; Those with diseased spots of 1 cm or less (number of rice seedlings;
n ₃ ) 3; Those with diseased spots of 2 cm or less (number of rice seedlings;
n ₄ ) 4; Those with diseased spots of 5 cm or less (number of rice seedlings;
n ₅ ) 5; Those with diseased spots of 10 cm or less (number of rice seedlings;
n ₆ ) 6; Those with diseased spots of 10 cm or more (number of rice seedlings;
_n7 ) Next, based on this investigation, the prevention rate of the test agent was calculated using the following formula. Prevention rate (%) / 100 = 1 - treatment area (0 x n ₁ + 1 x n ₂ + 2 x n ₃ + 3 x n ₄ + 4 x n ₅
+5×n ₆ +6×n ₇ )/untreated area (0×n ₁ +1×n ₂ +2×
n ₃ +3×n ₄ +4×n ₅ +5×n ₆ +6×n ₇ ) The results are shown in Table 1.

【table】

Claims (1)

[Claims] 1 formula [In the formula, R ¹ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, m is 0, 1, 2, or 3, and R ² represents an alkyl group having 1 to 4 carbon atoms, or a halogen atom; 4 alkyl group, benzyl group, cyclohexyl group, or [Formula] (R ³ represents an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, and n is 0, 1,
2 or 3. ), X ¹
represents an alkoxycarbonyl group having 2 to 5 carbon atoms, an aliphatic acyl group having 2 to 5 carbon atoms, a benzoyl group, or a cyano group. ] N-substituted aminomaleimides. 2 formulas Aminomaleimides represented ^by and the formula R ² -N=C=O [] [wherein R ² is an alkyl group having 1 to 4 carbon atoms, a benzyl group, a cyclohexyl group, or [Formula] (R ³ is an alkyl group having 1 to 4 carbon atoms) group, an alkoxy group having 1 to 4 carbon atoms, or a halogen atom, and n is 0, 1, 2 or 3. ] isocyanate represented by tertiary amine and/or quaternary amine.
The formula is characterized in that it is reacted in the presence of ammonium fluoride. A method for producing an N-substituted aminomaleimide represented by the formula (wherein R ¹ , R ² , X ¹ and m each have the same meanings as above).