Preparation process of 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl) aniline

Abstract

The invention discloses a preparation process of 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl) aniline, which comprises the following steps: carrying out docking reaction on 2-bromoheptafluoropropane and o-aminobenzotrifluoride under the catalysis of acid-binding agents sodium formate and tetrabutylammonium bromide and under the pressurization condition to obtain an intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl) aniline; and reacting the intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl) aniline with bromine to generate the product.

Description

Technical Field

[0001] The present invention relates to a preparation process of 2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)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 their 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 discovering compounds with selective toxicity. Although there are many literature reports, no highly active and safe products 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. Finally, in 2000, chlorantraniliprole was launched. 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 sold on the market: 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 of 2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)aniline.

[0005] To solve the above technical problem, the technical solution adopted by the present invention is:

[0006] A preparation process of 2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)aniline, characterized by comprising the following steps:

[0007] 2-Bromoheptafluoropropane and o-aminobenzotrifluoride are subjected to a docking reaction under pressure in the presence of an acid-binding agent sodium formate and tetrabutylammonium bromide as a catalyst to obtain an intermediate 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline;

[0008] The intermediate 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline reacts with bromine to form the product.

[0009] Specifically, it comprises the following steps:

[0010] (1) Preparation of the intermediate 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline

[0011] ① Docking reaction

[0012] In a high-pressure synthesis kettle, successively add 480 kg of o-aminobenzotrifluoride, 480 kg of water, 960 kg of ethyl acetate, 4.8 kg of tetrabutylammonium bromide, and 210 kg of sodium formate. Cool the jacket with circulating brine to below 10 °C, then add 850 kg of 2-bromoheptafluoropropane, introduce N2 to 0.4 MPa, and then heat the jacket with steam, raise the temperature to 80 - 90 °C, and keep the reaction for 6 h

[0013] ② Layers separation

[0014] After the reaction is completed, cool the jacket with circulating water to room temperature, separate the layers, and send the aqueous layer to the neutralization kettle;

[0015] ③ Solvent stripping

[0016] Transfer the organic layer to a solvent stripping kettle, start the W vacuum pump, heat the jacket with hot water, and carry out vacuum distillation at 40 - 60 °C and -0.09 MPa for 6 h; the distilled gas-phase ethyl acetate is condensed by a condenser using circulating brine and received in an EA receiving tank, and then filled into barrels for reuse in the next batch of docking reactions;

[0017] ④ Neutralization and water washing

[0018] After the solvent stripping is completed, transfer the oily 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 separate the layers; then wash once with 300 kg of water to obtain a crude product of yellow oily substance;

[0019] ⑤Rectification

[0020] The crude product is transferred to the rectification kettle. Start the Roots pump, pass steam through the jacket, conduct vacuum distillation, pass circulating water through the condenser, and conduct vacuum distillation at 120 - 130 °C and -0.095 MPa for 8 hours. The distillation gas phase is cooled and then enters the middle II receiving tank, and is filled into barrels to obtain 940 kg of light yellow oily substance, which is the intermediate 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline; (II)

[0022] In the synthesis kettle, 2000 kg of acetonitrile is pumped in by a pipeline pump, the stirring is started, and 800 kg of the intermediate II 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline is sucked in under vacuum, and the jacket is passed through with chilled brine to cool to 10 °C;

[0023] ②Bromination

[0024] 325 kg of bromine is pumped into the bromine metering tank by a pipeline pump and then dropped into the synthesis kettle. The jacket is passed through with chilled brine to control the temperature at 5 - 13 °C. After dropping, keep the temperature for reaction for 2 hours, then pass steam through the jacket and slowly raise the temperature to 30 - 40 °C and keep the temperature for 5 hours, and a large amount of solid gradually precipitates;

[0025] ③Crystallization and filtration

[0026] After the reaction is completed, pass chilled brine through the jacket and cool down to 10 - 15 °C and keep the temperature for 1 hour;

[0027] Start the feeding pump, pump the liquid material to the filter press for solid-liquid separation, and then blow with nitrogen for 20 minutes;

[0028] The pipeline pump pumps 100 kg of washing acetonitrile into the synthesis kettle, and the feeding pump pumps it to the filter press for washing, and then blows with nitrogen for 20 minutes;

[0029] Then wash again with 100 kg of acetonitrile in the same way, and blow with nitrogen for 2 hours until dry;

[0030] ④Solvent recovery

[0031] The acetonitrile mother liquor is transferred to the distillation kettle. The jacket of the distillation kettle is passed through with steam, and the W pump provides negative pressure. Vacuum distillation is carried out at 35 - 55 °C and -0.09 MPa for 6 hours. The distillation gas phase (mainly acetonitrile) is cooled by the condenser and then enters the receiving tank for recycling; the jacket is passed through with circulating water to cool down to 25 - 30 °C, and the distillation residue is filled into barrels for hazardous waste treatment;

[0032] ⑤Dissociation

[0033] Add 2000 kg of water to the dissociation kettle, start stirring, put in the filter press solid (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline hydrobromide), pass the jacket with chilled brine, add 30% sodium hydroxide solution dropwise at 30-40°C, adjust the pH to 8-9, and the solid gradually dissolves into an oil-water mixture. After completion, stir for 1 hour, re-measure the pH value, stand and separate, the lower oil layer (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline crude product) is transferred to the washing kettle, and the upper water layer (mainly sodium bromide aqueous solution) is sent to;

[0034] ⑥Washing

[0035] Add 900 kg of 10% sodium sulfite solution into the washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the secondary washing kettle, and the upper water layer to the wastewater tank;

[0036] Add 900 kg of 10% sodium sulfite solution to the secondary washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the water washing kettle, and the upper water layer to the wastewater tank;

[0037] ⑦ Washing

[0038] Add 500 kg of water to the washing kettle, stir for 1 hour, let stand to separate the layers, and barrel the lower oil layer and transport it to the warehouse to obtain 950 kg of light yellow liquid, which is the product 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline; the upper water layer is sent to the wastewater pool. DETAILED DESCRIPTION

[0039] Example 1

[0040] The present invention provides a preparation process of 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline, which comprises the following steps:

[0041] 2-Bromoheptafluoropropane and o-aminotrifluorotoluene were docked under pressure under the catalysis of acid-binding agents sodium formate and tetrabutylammonium bromide to obtain the intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline;

[0042] The intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline reacts with bromine to generate the product.

[0043] (I) Preparation of the intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline

[0044] ① Docking reaction

[0045] In a high-pressure synthesis kettle, successively add 480 kg of 2-aminobenzotrifluoride, 480 kg of water, 960 kg of ethyl acetate, 4.8 kg of tetrabutylammonium bromide, and 210 kg of sodium formate. Cool the jacket with chilled brine to below 10 °C, then add 850 kg of 2-bromoheptafluoropropane, introduce N2 to 0.4 MPa, and then pass steam through the jacket to raise the temperature to 80 - 90 °C and hold for reaction for 6 h.

[0046] ② Liquid separation

[0047] After the reaction is completed, pass circulating water through the jacket to cool to room temperature, separate the layers, and send the aqueous layer to the neutralization kettle.

[0048] ③ Solvent stripping

[0049] Transfer the organic layer to the solvent stripping kettle, start the W vacuum pump, pass hot water through the jacket, and carry out vacuum distillation at 40 - 60 °C and -0.09 MPa for 6 h. Condense the distillation gas phase of ethyl acetate with chilled brine through a condenser and transfer it to the EA receiving tank, then fill the barrels for reuse in the next batch of docking reactions.

[0050] ④ Neutralization and water washing

[0051] After solvent stripping is completed, transfer the oily substance to the neutralization kettle, cool the jacket with chilled brine to below 20 °C, add 900 kg of 10% sodium carbonate solution dropwise to adjust the pH to 7 - 8, and separate the layers; then wash once with 300 kg of water to obtain the crude product of yellow oily substance.

[0052] ⑤ Rectification

[0053] Transfer the crude product to the rectification kettle, start the Roots pump, pass steam through the jacket, carry out vacuum distillation, pass circulating water through the condenser, and carry out vacuum distillation at 120 - 130 °C and -0.095 MPa for 8 h. Cool the distillation gas phase and transfer it to the Middle II receiving tank, then fill the barrels to obtain 940 kg of light yellow oily substance, which is the intermediate 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline. (Two)

[0055] In the synthesis kettle, pump 2000 kg of acetonitrile into it with a pipeline pump, start stirring, and suck 800 kg of the intermediate II 4-(perfluoropropan-2-yl)-2-(trifluoromethyl)aniline into it under vacuum. Cool the jacket with chilled brine to 10 °C.

[0056] ② Bromination

[0057] Pump 325 kg of bromine into the bromine metering tank with a pipeline pump and drip it into the synthesis kettle. Control the temperature of the jacket with chilled brine at 5 - 13 °C. After dripping, hold for reaction for 2 h, then pass steam through the jacket and slowly raise the temperature to 30 - 40 °C and hold for 5 h, and a large amount of solid gradually precipitates.

[0058] ③ Crystal precipitation and filtration

[0059] After the reaction is completed, pass the jacket through chilled brine, cool to 10-15°C, and keep warm for 1 hour;

[0060] Turn on the feed pump to pump the feed liquid to the filter press for solid-liquid separation, and then blow nitrogen for 20 minutes;

[0061] The pipeline pump pumps 100 kg of washing acetonitrile into the synthesis kettle, and the feed pump pumps it to the filter press for washing, and then blows nitrogen for 20 minutes;

[0062] Then wash it again with 100 kg of acetonitrile and blow it with nitrogen for 2 h until it is dry;

[0063] ④Recover solvent

[0064] The acetonitrile mother liquor is transferred to the distillation kettle, the jacket of the distillation kettle is passed through steam, and the W pump provides negative pressure. The distillation is carried out at 35-55°C and -0.09MPa under reduced pressure for 6 hours. The distillation gas phase (mainly acetonitrile) is cooled by the condenser and enters the receiving tank for recycling. The jacket is cooled by circulating water to 25-30°C, and the distillation residue is barreled and treated as hazardous waste;

[0065] ⑤ Dissociation

[0066] Add 2000 kg of water to the dissociation kettle, start stirring, put in the filter press solid (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline hydrobromide), pass the jacket with chilled brine, add 30% sodium hydroxide solution dropwise at 30-40°C, adjust the pH to 8-9, and the solid gradually dissolves into an oil-water mixture. After completion, stir for 1 hour, re-measure the pH value, stand and separate, the lower oil layer (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline crude product) is transferred to the washing kettle, and the upper water layer (mainly sodium bromide aqueous solution) is sent to;

[0067] ⑥Washing

[0068] Add 900 kg of 10% sodium sulfite solution into the washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the secondary washing kettle, and the upper water layer to the wastewater tank;

[0069] Add 900 kg of 10% sodium sulfite solution to the secondary washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the water washing kettle, and the upper water layer to the wastewater tank;

[0070] ⑦ Washing

[0071] Add 500 kg of water to the washing kettle, stir for 1 hour, let stand to separate the layers, and barrel the lower oil layer and transport it to the warehouse to obtain 950 kg of light yellow liquid, which is the product 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline; the upper water layer is sent to the wastewater pool.

[0072] 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. A process for preparing 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline, characterized in that: The method comprises the following steps: 2-bromoheptafluoropropane and o-aminotrifluorotoluene are subjected to docking reaction under pressure under the catalysis of acid-binding agents sodium formate and tetrabutylammonium bromide to obtain an intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline; The intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline reacts with bromine to generate the product.

2. The process for preparing 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline according to claim 1, characterized in that: The following steps are involved: Preparation of intermediate 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline; Docking reaction: in a high-pressure synthesis reactor, 480 kg of o-aminotrifluorotoluene, 480 kg of water, 960 kg of ethyl acetate, 4.8 kg of tetrabutylammonium bromide, and 210 kg of sodium formate were added in sequence, and the jacket was cooled to below 10°C by passing refrigerated brine, and then 850 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 hot water through the jacket, and perform vacuum distillation at 40--60℃, -0.09MPa for 6h; vacuum distillation; the distilled gaseous ethyl acetate is condensed into the EA receiving tank using frozen brine through the condenser, 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 120-130°C and -0.095MPa for 8 hours. The distilled gas phase is cooled and then enters the intermediate II receiving tank, and is barreled to obtain 940 kg of a light yellow oily substance, which is the intermediate di-4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline; In the synthesis reactor, 2000 kg of acetonitrile was pumped into the reactor using a pipeline pump, stirring was started, 800 kg of the intermediate II 4-(perfluoropropane-2-yl)-2-(trifluoromethyl)aniline was vacuum-inhaled, and the jacket was cooled to 10°C by passing refrigerated brine; Bromination: 325 kg of bromine is pumped into the bromine metering tank through a pipeline pump, and then dripped into the synthesis reactor. The jacket is passed through frozen brine to control the temperature at 5-13°C. After dripping, the reaction is kept warm for 2 hours, and then the jacket is passed through steam, and the temperature is slowly raised to 30-40°C and kept warm for 5 hours, and a large amount of solids are gradually precipitated; After crystallization and filtration, the reaction is complete, the jacket is passed through chilled brine, the temperature is lowered to 10-15°C, and the temperature is kept for 1 hour; Turn on the feed pump to pump the feed liquid to the filter press for solid-liquid separation, and then blow nitrogen for 20 minutes; The pipeline pump pumps 100 kg of washing acetonitrile into the synthesis kettle, and the feed pump pumps it to the filter press for washing, and then blows nitrogen for 20 minutes; Then wash it again with 100 kg of acetonitrile and blow it with nitrogen for 2 h until it is dry; The solvent is recovered, and the acetonitrile mother liquor is transferred to the distillation kettle. The jacket of the distillation kettle is passed through steam, and the W pump provides negative pressure. The distillation is carried out at 35-55°C and -0.09MPa under reduced pressure for 6 hours. The distillation gas phase (mainly acetonitrile) is cooled by the condenser and enters the receiving tank for recycling. The jacket is passed through circulating water to cool down to 25--30°C, and the distillation residue is barreled and treated as hazardous waste; Dissociation: add 2000 kg of water to the dissociation kettle, start stirring, put in the filter press solid (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline hydrobromide), pass the jacket with frozen brine, add 30% sodium hydroxide solution dropwise at 30-40°C, adjust the pH to 8-9, and the solid gradually dissolves into an oil-water mixture. After completion, stir for 1 hour, re-measure the pH value, stand and separate, the lower oil layer (2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline crude product) is transferred to the washing kettle, and the upper water layer (mainly sodium bromide aqueous solution) is sent to; Washing: add 900 kg of 10% sodium sulfite solution into the washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the secondary washing kettle, and the upper water layer to the wastewater tank; Add 900 kg of 10% sodium sulfite solution to the secondary washing kettle, stir for 1 hour, let stand to separate the layers, transfer the lower oil layer to the water washing kettle, and the upper water layer to the wastewater tank; Water washing: add 500 kg of water to the water washing kettle, stir for 1 hour, let stand to separate the layers, and barrel the lower oil layer and transport it to the warehouse to obtain 950 kg of light yellow liquid, which is the product 2-bromo-4-(perfluoropropane-2-yl)-6-(trifluoromethyl)aniline; the upper water layer goes to the wastewater pool.