Preparation process of 2-methyl-4-(heptafluoroisopropyl) aniline

Abstract

The invention discloses a preparation process of 2-methyl-4-(heptafluoroisopropyl) aniline, which is characterized in that 2-bromoheptafluoropropane and o-methylaniline are subjected to docking reaction under the catalysis of acid-binding agents of sodium formate and tetrabutylammonium bromide and under the pressurization condition to obtain the 2-methyl-4-(heptafluoroisopropyl) aniline.

Description

Technical Field

[0001] The present invention relates to a preparation process of 2-methyl-4-(heptafluoroisopropyl)aniline, belonging to the chemical industry field. Background Art

[0002] In the mid-20th century, American scientists extracted the plant alkaloid ryanodine from the South American Flacourtiaceae shrub Ryania speciosa, which can be used as a natural insecticide and has a history of more than 50 years. This plant is highly poisonous to humans and animals. Local Indians often mashed it and applied it to arrowheads to make poisoned arrows. After being shot, animals showed convulsions and tension in the whole body muscles and finally died like zombies. Its extract is very effective against Lepidoptera pests, including European corn borer, sugarcane borer, apple leafroller, apple fruit borer, gypsy moth, etc. However, due to the high toxicity of ryanodine to humans and animals, causing rigid paralysis in mammals, its popularization and application are restricted. Previous studies on ryanodine mainly focused on structural modification in the hope of finding compounds with selective toxicity. Although there are many literature reports, no products with high activity and safety have been obtained through structural modification so far.

[0003] In 1989, Dr. Tsuda in Japan reported a chemically synthesized compound acting on the ryanodine receptor in his doctoral thesis, which has bactericidal and herbicidal activities but no insecticidal activity. The Japanese pesticide company carried out a large amount of R & D work on this compound. During this period, Bayer also participated. Finally, in 1998, the first ryanodine receptor modulator insecticide - flubendiamide was reported. In order to bypass the patents of the Japanese pesticide company and Bayer, DuPont made significant modifications to the active structure and groups, and finally launched chlorantraniliprole in 2000. These two compounds have excellent control effects on almost all Lepidoptera pests, but are ineffective against pests of other orders. Flubendiamide was first listed in Japan in 2007 (registered for various vegetables and fruit trees), and successively obtained registrations in India (registered for rice and cotton), South Korea (vegetables, fruit trees and rice), and China in 2008, and gradually began to be on the market for sale: Chlorantraniliprole was listed in the Philippines in 2007 (rice), and then promoted and sold globally. Its market launch schedule, registered crops, and promotion efforts are better than those of flubendiamide. DuPont's cyantraniliprole was launched in 2012. This is the second-generation ryanodine receptor inhibitor insecticide successfully developed by DuPont after chlorantraniliprole. Cyantraniliprole is formed by changing various polar groups on the benzene ring, is more efficient, has a wider range of applicable crops, and can effectively control Lepidoptera, Hemiptera and Coleoptera pests. At present, many companies are still researching this type of compound, and some varieties have made breakthroughs in the insecticidal spectrum. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a preparation process for 2-methyl-4-(heptafluoroisopropyl)aniline.

[0005] To solve the above technical problem, the technical solution adopted by the present invention is: The preparation process for 2-methyl-4-(heptafluoroisopropyl)aniline includes the following steps:

[0006] 2-bromoheptafluoropropane and o-methylaniline are subjected to a docking reaction under the catalysis of an acid-binding agent sodium formate and tetrabutylammonium bromide under pressure conditions to obtain 2-methyl-4-(heptafluoroisopropyl)aniline.

[0007] Furthermore, it includes the following steps:

[0008] ① Docking reaction

[0009] In a high-pressure synthesis kettle, successively add 400 kg of o-methylaniline, 400 kg of water, 1000 kg of ethyl acetate, 4 kg of tetrabutylammonium bromide, and 260 kg of sodium formate. Cool the jacket with circulating brine to below 10°C, then add 960 kg of 2-bromoheptafluoropropane, pass N2 to 0.4 MPa, then pass steam through the jacket, heat up to 80 - 90°C, and keep the reaction for 6 h;

[0010] ② Layering

[0011] After the reaction is completed, cool the jacket with circulating water to room temperature, layer, and send the water layer to the neutralization kettle;

[0012] ③ Desolventization

[0013] Transfer the organic layer to a desolventization kettle, start the W vacuum pump, cool the condenser with circulating brine, and pass hot water through the jacket. Under the conditions of 40 - 60°C and -0.09 MPa, carry out vacuum distillation for 6 h; The distilled gas-phase ethyl acetate is condensed by circulating brine in the condenser and received in the EA receiving tank, and then packed and reused for the next batch of docking reactions;

[0014] ④ Neutralization and water washing

[0015] After desolventization is completed, transfer the oil-like substance to the neutralization kettle, cool the jacket with circulating brine to below 20°C, dropwise add 900 kg of 10% sodium carbonate solution to adjust the pH to 7 - 8, and layer; Then wash once with 300 kg of water to obtain a crude product of yellow oil;

[0016] ⑤ Rectification

[0017] Transfer the crude product to a rectification kettle, start the Roots pump, pass steam through the jacket, carry out vacuum distillation, and cool the condenser with circulating water. Under the conditions of 100 - 110°C and -0.095 MPa, carry out vacuum distillation for 8 h. The distilled gas-phase is cooled and then enters the product receiving tank, and then packed to obtain 985 kg of light yellow oil-like substance, which is the product 2-methyl-4-(heptafluoroisopropyl). Specific embodiments

[0018] Example 1

[0019] This example provides a preparation process for 2-methyl-4-(heptafluoroisopropyl)aniline, and the technical principle is as follows:

[0020] 2-Bromoheptafluoropropane and o-methylaniline are subjected to a docking reaction under the catalysis of an acid-binding agent sodium formate and tetrabutylammonium bromide under pressurized conditions to obtain 2-methyl-4-(heptafluoroisopropyl)aniline.

[0021] Specifically, it includes the following steps:

[0022] ① Docking reaction

[0023] In a high-pressure synthesis kettle, 400 kg of o-methylaniline, 400 kg of water, 1000 kg of ethyl acetate, 4 kg of tetrabutylammonium bromide, and 260 kg of sodium formate are sequentially added. The jacket is passed through with chilled brine to cool down to below 10 °C, and then 960 kg of 2-bromoheptafluoropropane is added. Nitrogen is passed through to 0.4 MPa, and then steam is passed through the jacket to heat up to 80 - 90 °C, and the reaction is carried out under insulation for 6 h;

[0024] ② Layers separation

[0025] After the reaction is completed, the jacket is passed through with circulating water to cool down to room temperature, and layers are separated. The aqueous layer goes to the neutralization kettle;

[0026] ③ Desolventization

[0027] The organic layer is transferred to a desolventization kettle. The W vacuum pump is started, the condenser is passed through with chilled brine, and the jacket is passed through with hot water. Under the conditions of 40 - 60 °C and -0.09 MPa, vacuum distillation is carried out for 6 h; The distilled gas-phase ethyl acetate is condensed by chilled brine in the condenser and received in the EA receiving tank, and then filled into barrels for reuse in the next batch of docking reactions;

[0028] ④ Neutralization and water washing

[0029] After desolventization is completed, the oily substance is transferred to the neutralization kettle. The jacket is passed through with chilled brine to cool down to below 20 °C, and 900 kg of 10% sodium carbonate solution is added dropwise to adjust the pH = 7 - 8, and then layers are separated; Then it is washed once with 300 kg of water to obtain a crude product of yellow oily substance;

[0030] ⑤ Rectification

[0031] The crude product is transferred to a rectification kettle. The Roots pump is started, the jacket is passed through with steam, and vacuum distillation is carried out. The condenser is passed through with circulating water. Under the conditions of 100 - 110 °C and -0.095 MPa, vacuum distillation is carried out for 8 h. The distilled gas-phase is cooled and then enters the product receiving tank, and is filled into barrels to obtain 985 kg of light yellow oily substance, which is the product 2-methyl-4-(heptafluoroisopropyl)

[0032] Certainly, the above description is not a limitation of the present invention, nor is the present invention limited to the above examples. Any changes, modifications, additions or substitutions made by those of ordinary skill in the art within the scope of the essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. The preparation process of 2-methyl-4-(heptafluoroisopropyl)aniline is characterized in that: The following steps are involved: 2-Bromoheptafluoropropane and o-methylaniline are subjected to docking reaction under pressure under the catalysis of acid-binding agents sodium formate and tetrabutylammonium bromide to obtain 2-methyl-4-(heptafluoroisopropyl)aniline.

2. The preparation process according to claim 1, characterized in that: The following steps are involved: Docking reaction: in a high-pressure synthesis reactor, 400 kg of o-methylaniline, 400 kg of water, 1000 kg of ethyl acetate, 4 kg of tetrabutylammonium bromide, and 260 kg of sodium formate were added in sequence, and the jacket was cooled to below 10°C by passing refrigerated brine, and then 960 kg of 2-bromoheptafluoropropane was added, and N2 was passed to 0.4 MPa, and then steam was passed through the jacket, and the temperature was raised to 80-90°C, and the reaction was kept warm for 6 hours; After the reaction is completed, the jacket is cooled to room temperature by circulating water, and the layers are separated, and the water layer is sent to the neutralization kettle; Desolventize, transfer the organic layer to the desolventize kettle, turn on the W vacuum pump, pass the condenser through the frozen brine, pass the jacket through hot water, and distill under reduced pressure at 40--60℃, -0.09MPa for 6h; the distilled gaseous ethyl acetate is condensed into the EA receiving tank through the condenser with frozen brine, and then barreled and reused for the next batch of docking reaction; After neutralization and water washing, the oily substance is transferred to a neutralization kettle, and the jacket is cooled to below 20°C by passing frozen brine, and 900 kg of 10% sodium carbonate solution is added dropwise to adjust the pH to 7--8, and the mixture is separated into layers; then the mixture is washed once with 300 kg of water to obtain a crude yellow oily substance; Distillation: the crude product is transferred to the distillation kettle, the Roots pump is turned on, steam is passed through the jacket, vacuum distillation is performed, circulating water is passed through the condenser, and reduced pressure distillation is performed at 100-110℃, -0.095MPa for 8h. The distilled gas phase enters the product receiving tank after cooling and is loaded into barrels to obtain 985kg of light yellow oily substance, which is the product di-2-methyl-4-(heptafluoroisopropyl)aniline.