JPH0481582B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to a novel 2,5-dihalo-3-trifluoromethylaniline useful as a manufacturing intermediate for pharmaceuticals, agriculture, etc., and a method for manufacturing the same. The compound of the present invention is particularly represented by the following structural formula:
It is an intermediate of benzoyl urea derivatives useful as insecticides with excellent insecticidal efficacy. (Prior art) 2,5-difluoro-3-trifluoromethylaniline is described in J.Med.Chem.7(4) p572-3 (1964) and is derived from N-phenyl carbamate. . Many N-benzoyl-N'-phenylurea insecticides have been reported, but most of them are compounds in which the phenyl group is substituted at the 4-position. It can be said that the activity is being searched for. As a compound having a halogen atom and a trifluoromethyl group similar to the compounds of the present invention as a substituent of a phenyl group, a compound represented by the following structural formula is typical. (Problems to be Solved by the Invention) The present inventors conducted research to find a compound with even better insecticidal action than the above-mentioned known compounds, and found that 2,5-dihalo- 3
-We have discovered a trifluoromethylphenylurea derivative. The present invention was carried out in order to provide an industrially advantageous method for producing a novel 2,5-dihalo-3-trifluoromethylaniline useful as an intermediate thereof. (Means to solve the problem) General formula (In the formula, X and Y represent a halogen atom. However, at the same time, they do not represent a fluorine atom.) By reducing the compound represented by the general formula The compound represented by can be produced with good yield. Reduction methods include reduction with iron in the presence of an acid, catalytic reduction with hydrogen in the presence of palladium-carbon, and reduction with sodium hydrosulfite. Any method used for the reduction of can be applied, and the compound of the present invention can be produced with good yield by any method. The nitrobenzene derivative represented by the general formula () is also a novel compound described at the end of the literature, and can be produced by nitration of the corresponding 2,5-dihalo-trifluoromethylbenzene by a conventional method. Further, as shown in the reaction formula below, a fluorine atom can also be introduced into X by performing a halogen exchange reaction. (X' and Y' represent a chlorine atom or a bromine atom.) (Examples) Next, the compounds of the present invention will be explained in more detail with reference to Examples. Example 1 Synthesis of 2,5-dichloro-3-trifluoromethylaniline 2,5-dichlorobenzotrifluoride 38g
A mixed acid (a mixture of 15 g of fuming nitric acid and 50 g of concentrated sulfuric acid) was gradually added dropwise to a mixture of 15 g of fuming nitric acid and 50 g of concentrated sulfuric acid while cooling the mixture with water so that the reaction temperature did not rise above 15-16°C. After the dropwise addition was completed, the reaction solution was gradually heated to 50°C and stirred at the same temperature for 3 hours. After the reaction is complete, separate the organic layer and dissolve the organic layer in 200ml of benzene.
The benzene layer was washed with water, washed with heavy sodium chloride, washed with water, and then dried over anhydrous magnesium sulfate. After removing the solvent, 2,5-dichloro-3 was obtained by distillation under reduced pressure.
-40.5 g of nitrobenzotrifluoride were obtained.
bp124-126℃/18-19mm (mp46.7-47.3℃) 43g of the obtained 2,5-dichloro-3-nitrobenzotrifluoride was mixed with 40g of iron powder, 20g of acetic acid, and water.
The mixture was mixed with 360 ml and stirred for 3 hours under heating (oil bath temperature: 120°C). After the reaction solution was cooled to room temperature, 200 ml of ethyl acetate was added as a solvent, and insoluble materials were separated. The insoluble matter was further thoroughly washed with 200 ml of ethyl acetate, the liquid and the washing liquid were combined, and the organic layer was separated. Wash the organic layer with water,
After washing with heavy sodium chloride and water, it was dried over anhydrous magnesium sulfate. After the solvent was distilled off, 35 g of aniline, the target product, was obtained by distillation under reduced pressure. bp130℃/18mmHg Example 2 Synthesis of 5-chloro-2-fluoro-3-trifluoromethylaniline 27 g of 2,5-dichloro-3-nitrobenzotrifluoride and 150 g of dried dimethylformamide
ml, 15 g of potassium fluoride was added thereto, and the mixture was stirred under heating under reflux for 7 hours. After cooling the reaction solution to room temperature, add water
The organic layer was extracted with ethyl ether. The ethyl ether layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was distilled off, and then distilled under reduced pressure to obtain 15 g of 5-chloro-2-fluoro-3-nitrobenzotrifluoride. bp100−115
°C/16-17mmHg 11g of 5-chloro-2-fluoro-3-nitrobenzotrifluoride, 10g of iron powder, 5g of acetic acid, water
The mixture was mixed with 100 ml and heated under reflux for 3 hours. After the reaction solution was cooled to room temperature, 100 ml of ethyl acetate was added to separate the insoluble matter. The insoluble matter was further washed with 100 ml of ethyl acetate, the liquid and the washing liquid were combined, and the organic layer was separated.
The organic layer was washed with water, washed with heavy sodium chloride, and dried over anhydrous magnesium sulfate after washing with water. After distilling off the solvent, 7 g of aniline, the target product, was obtained by distillation under reduced pressure. b.
p.103-110℃/20mmHg Example 3 Synthesis of 5-bromo-2-chloro-3-trifluoromethylaniline Dissolve 9 g of sodium nitrite in 80 ml of concentrated sulfuric acid,
Chloro-3-trifluoromethylaniline 19.5g
A 40 ml solution of acetic acid was gradually added dropwise so that the reaction temperature did not rise above 30°C, and after the addition was completed, the mixture was stirred at room temperature for 1 hour. 60 g of cuprous bromide and 250 g of 47% hydrobromic acid
ml of the mixture was stirred and boiled in an oil bath at approximately 200°C.
While the above diazonium solution was gradually added dropwise, steam distillation was carried out at the same time. The distillate and distillation residue were extracted with carbon tetrachloride, and the extract was washed with water, sodium bicarbonate, and water, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, 5-bromo-
16.2 g of 2-chlorobenzotrifluoride was obtained. bp90-91℃/23mmHg To a mixture of 15g of 5-bromo-2-chlorobenzotrifluoride and 20ml of concentrated sulfuric acid, gradually drop a mixed acid (5g of fuming nitric acid and 10ml of concentrated sulfuric acid) so that the reaction temperature does not rise above 30℃. After completion of the dropwise addition, the mixture was stirred at 40 to 50°C for 6 hours. 500 ml of ice water was added to the reaction solution, and extracted with methylene chloride. The extract was washed with water, sodium chloride, and water, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography (solvent: n-hexane) to obtain 12 g of 5-bromo-2-chloro-3-nitrobenzotrifluoride. bp146−148℃/
24mmHg A mixture of 11g of iron powder, 7g of acetic acid, and 120ml of water is heated to approx.
Stir at ℃, add 11 g of 5-bromo-2-chloro-3-nitrobenzotrifluoride, stir for 3 hours, cool to room temperature, add 50 ml of ethyl acetate, filter, and remove insoluble matter with ethyl acetate. Washed. The liquid and washing liquid were combined and the organic layer was separated, washed with water, washed with sodium bicarbonate, washed with water, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, 9.0 g of distilled 5-bromo-2-chloro-3-trifluoromethylaniline was obtained. bp148−150℃/21mm
Hg Example 4 Synthesis of 2-bromo-5-chloro-3-trifluoromethylaniline Dissolve 9.0g of sodium nitrite in 80ml of concentrated sulfuric acid,
-Chloro-2-trifluoromethylaniline 19.5
40 ml of acetic acid solution was gradually added dropwise so that the reaction temperature did not rise above 30°C, and after the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. 60g cuprous bromide and 47% hydrobromic acid
250 ml of the mixture was stirred and boiled in an oil bath at about 200° C., and the above diazonium solution was gradually added dropwise while steam distillation was simultaneously carried out. The distillate and distillation residue were extracted with methylene chloride, and the extract was washed with water, sodium chloride, and water, and then dried over anhydrous magnesium sulfate. After the solvent was distilled off, 19.7 g of 2-bromo-5-chlorobenzotrifluoride was obtained by distillation.
I got it. bp97-102℃/28mmHg 2-bromo5-chlorobenzotrifluoride
Mix 13.0 g of concentrated sulfuric acid with 40 ml of mixed acid (fuming nitric acid).
4.5 g of concentrated sulfuric acid and 5 ml of concentrated sulfuric acid were gradually added dropwise while maintaining the reaction temperature at about 50°C, and after the addition was completed, the mixture was stirred at the same temperature for 5 hours. After the reaction solution was added to 500 ml of ice water, the organic layer was extracted with methylene chloride. Wash the extract with water,
After washing with heavy sodium chloride and water, it was dried over anhydrous magnesium sulfate. After removing the solvent, it is distilled to give 2-
8.7 g of bromo-5-chloro-3-nitrobenzotrifluoride was obtained. bp146−148℃/26mmHg
mp61−65℃ 2 in a mixture of 9.0 g of iron powder, 4.2 g of acetic acid, and 100 ml of water.
After adding 8.0 g of -bromo-5-chloro-3-nitrobenzotrifluoride and stirring at about 90°C for 2 hours, the mixture was cooled to room temperature, added with 100 ml of ethyl acetate, and filtered. After thoroughly washing the insoluble matter with ethyl acetate,
The liquid and washing liquid were combined, and the organic layer was separated, washed with water, washed with sodium bicarbonate, washed with water, and then dried over anhydrous magnesium sulfate. After the solvent was distilled off, 6.5 g of 2-bromo-5-chloro-3-trifluoromethylaniline was obtained by distillation. bp150−153℃/24mm
Hg Example 5 Synthesis of 2-chloro-5-fluoro-3-trifluoromethylaniline 13.5 g of sodium nitrite was dissolved in 90 ml of concentrated sulfuric acid, and 30.0 g of 4-chloro-3-trifluoromethylaniline was gradually added so that the reaction temperature did not rise above 30°C. After stirring at the same temperature for 1 hour, 150ml of ice water
Insoluble matter was separated. A 42% tetrafluoroboric acid solution was added to the solution while stirring while cooling with ice water, and after stirring for 30 minutes, the precipitated crystals were filtered, washed with a small amount of cold water, further washed with methanol and ether, and then air-dried. 40.7 g of -chloro-3-trifluoromethylbenzene-1-diazonium tetrafluoroborate was obtained. bp165−
170℃ Decompose 40g of the above diazonium salt in an oil bath at about 200℃ and distill the resulting oil to obtain 2-chloro-
23.4 g of 5-fluorobenzotrifluoride was obtained. bp53℃/25mmHg Mixed acid (mixture of 1.3g of fuming nitric acid and 2ml of concentrated sulfuric acid) was added to a mixture of 3.0g of 2-chloro-5-fluorobenzotrifluoride and 10ml of concentrated sulfuric acid at a reaction temperature of
The mixture was gradually added dropwise so that the temperature did not exceed 50°C. After the dropwise addition was completed, the mixture was stirred at about 50°C for 4 hours, left to stand overnight at room temperature, and then added to 200 ml of ice water and extracted with methylene chloride. After washing the extract with water, washing with heavy soap, and washing with water,
Dry over anhydrous magnesium sulfate. After removing the solvent, it is distilled to give 2-chloro-5-fluoro-3
-2.7 g of nitrobenzotrifluoride were obtained.
bp108-112℃/22mmHg 2-
2.5 g of chloro-5-fluoro-3-nitrobenzotrifluoride was added and stirred at about 80°C for 3 hours.
After cooling to room temperature, 30 ml of ethyl acetate was added and filtered, and insoluble materials were thoroughly washed with ethyl acetate. The liquid and the washing liquid were combined, washed with water, washed with heavy sodium chloride, washed with water, and then dried over anhydrous magnesium sulfate. After the solvent was distilled off, 1.7 g of 2-chloro-5-fluoro-3-trifluoromethylaniline was obtained by distillation. bp112℃/24mmHg (Effect of the invention) The compound of the present invention has the general formula (In the formula, R ₁ and R ₂ represent a hydrogen atom, a halogen atom, or a methyl group.) A benzoyl urea derivative represented by the above general formula () can be produced by reacting with a compound represented by . As shown in the following test examples, the benzoyl urea derivatives are superior to known compounds in terms of insecticidal efficacy, ovicidal action, insecticidal spectrum, etc. Test Example 1 Efficacy against Spodoptera spp. The test compound was formulated into a wettable powder and diluted with water to prepare a treatment chemical solution. Sweet potato leaves were immersed in the chemical solution for 30 seconds, and after air-drying, five third instar larvae of Spodoptera larvae
The leaves were placed in a 9 cm diameter chaaret containing the head and covered with a glass lid. The temperature of the chaare is 25℃ and the humidity is
The insecticidal rate was determined after 5 days by placing it in a 65% constant temperature room and determining the LC ₉₅ . The results are shown in Table 1.

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Claims (1)

[Claims] 1. General formula (In the formula, X and Y represent halogen atoms. However, X and Y are not fluorine atoms at the same time.) 2 General formula (In the formula, X and Y represent halogen atoms. However, X
and Y are not fluorine atoms at the same time. ) A general formula characterized by reducing the compound represented by A method for producing a compound represented by the formula (wherein X and Y have the same meanings as above).