Synthesis method of 2,6-difluoroaniline

Abstract

The invention discloses a synthetic method of 2,6-difluoroaniline, having the following steps: ①2,6-difluorobenzamide and trichloroisocyanuric acid are in a first solvent, and a first reaction is carried out at a first temperature, and then an intermediate is obtained through a first post-processing; ②the intermediate obtained in step ① is in an alkaline solution, and a second reaction is carried out at a second temperature, and then 2,6-difluoroaniline is obtained through a second post-processing. The method of the present invention can be separated in advance to obtain an intermediate chloro product, so that the risk of material impact can be avoided, and the safety is relatively high, and trichloroisocyanuric acid is stable and easy to measure, and compared with the sodium hypochlorite method, the operation is simpler. The method of the present invention can also obtain 2,6-difluoroaniline with higher purity without rectification, which not only greatly simplifies post-processing, but also produces less waste water, is more environmentally friendly, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide intermediate synthesis, and particularly relates to a method for synthesizing 2,6-difluoroaniline. Background Art

[0002] 2,6-Difluoroaniline is an important pesticide intermediate that can be used to prepare pesticides such as bispyribac and flumet. Bispyribac is mainly used to control broadleaf weeds in winter wheat fields, such as galium, chickweed, Polygonum weeds, and Asteraceae weeds. Flumet is mainly used to control annual and perennial broadleaf weeds in corn, soybean, wheat, barley, clover, alfalfa and other fields, such as shepherd's purse, small-flowered sugar mustard, Lepidium, Artemisia selengensis, Polygonum, Veronica, Xanthium sibiricum, Solanum nigrum, Amaranthus retroflexus, Datura, etc. It also has a certain inhibitory effect on young grass weeds.

[0003] At present, the methods for synthesizing 2,6-difluoroaniline all use 2,6-difluorobenzamide as the starting material, firstly perform a degradation reaction with sodium hypochlorite in a sodium hydroxide aqueous solution, then obtain a crude product by steam distillation, and finally obtain a pure product by rectification [see Chinese patent documents CN102351713A, CN111777515A, CN112457198A, CN113501762A, CN113929583A], and the reaction formula is as follows:

[0004] .

[0005] The shortcomings of this method are: (1) Sodium hypochlorite is difficult to measure accurately and the operation is complicated; (2) There is a risk of material impact and the safety is low; (3) A large amount of high-salt wastewater will be generated, which will seriously pollute the environment; (4) Although the purity is relatively high, it needs to be processed through steam distillation and rectification, which makes the post-processing more complicated. Summary of the invention

[0006] The purpose of the present invention is to solve the above problems and provide a method for synthesizing 2,6-difluoroaniline which is simple to operate, highly safe, more environmentally friendly and simple to post-process.

[0007] The technical solution for achieving the purpose of the present invention is: a method for synthesizing 2,6-difluoroaniline, comprising the following steps:

[0008] ① 2,6-difluorobenzamide and trichloroisocyanuric acid are subjected to a first reaction in a first solvent at a first temperature, and then subjected to a first post-treatment to obtain an intermediate.

[0009] ② The intermediate obtained in step ① is subjected to a second reaction in an alkaline solution at a second temperature, and then subjected to a second post-treatment to obtain 2,6-difluoroaniline.

[0010] The reaction formula is as follows:

[0011] .

[0012] In the above step ①, the molar ratio of the 2,6-difluorobenzamide to the trichloroisocyanuric acid is 1:0.3 to 1:0.4.

[0013] In the above step ①, the first solvent is one of an alcohol solvent, an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, and an ester solvent, preferably an alcohol solvent, and more preferably methanol.

[0014] In the above step ①, the first temperature is 10-40°C, preferably 25°C.

[0015] In the above step ①, the time of the first reaction is 0.5 to 3 hours, preferably 1 hour.

[0016] In the above step ①, the first post-treatment is suction filtration, and the filtrate is dried after the solvent is removed.

[0017] The drying temperature is 20-50°C, preferably 35°C.

[0018] In the above step ②, the concentration of the alkaline solution is 10wt% to 50wt%, preferably 30wt%.

[0019] In the above step ②, the alkaline solution is a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution, preferably a potassium hydroxide aqueous solution.

[0020] In the above step ②, the molar ratio of the alkali in the alkaline solution to the 2,6-difluorobenzamide in step ① is 2:1 to 5:1, preferably 3:1.

[0021] In the above step ②, the second temperature is 50-100°C, preferably 90°C.

[0022] In the above step ②, the time of the second reaction is 2 to 6 hours, preferably 3 hours.

[0023] In the above step ②, the second post-treatment is cooling to room temperature (15-25° C.), adding a second solvent for extraction, and removing the solvent from the organic layer after extraction.

[0024] The second solvent is a halogenated hydrocarbon solvent or an aromatic hydrocarbon solvent, preferably a halogenated hydrocarbon solvent, and more preferably dichloromethane.

[0025] The present invention has the positive effects:

[0026] (1) The method of the present invention can first separate the intermediate chlorinated product, which can avoid the risk of material impact and has higher safety. In addition, trichloroisocyanuric acid is stable and easy to measure. Compared with the sodium hypochlorite method, the operation is simpler.

[0027] (2) The method of the present invention can obtain 2,6-difluoroaniline with high purity without distillation, which not only greatly simplifies the post-treatment, but also generates less wastewater, is more environmentally friendly, and is suitable for industrial production. DETAILED DESCRIPTION

[0028] (Example 1)

[0029] The synthetic method of 2,6-difluoroaniline of the present embodiment comprises the following steps:

[0030] ① Add 78.5 g (0.5 mol) of 2,6-difluorobenzamide and 300 mL of methanol into a 500 mL four-necked bottle. After stirring to dissolve, add 38.8 g (0.167 mol) of trichloroisocyanuric acid. A white solid is generated. Keep the reaction at 25 °C for 1 h.

[0031] After the reaction was completed, the solution was filtered, the solvent was removed from the filtrate under reduced pressure, and then dried at 35° C. to obtain 95.7 g of chlorinated product.

[0032] ② Add 280.5 g of 30 wt% potassium hydroxide aqueous solution (containing 1.5 mol of potassium hydroxide) and 95.7 g of the chlorinated product obtained in step ① into a 1000 mL four-necked bottle, stir to dissolve, and keep warm at 90°C for 3 h.

[0033] After the reaction was completed, the mixture was cooled to 20°C, 250 mL of dichloromethane was added for extraction, and the lower organic layer was separated. After the solvent was removed from the organic layer, 61.8 g of 2,6-difluoroaniline was obtained with a yield of 95.8% and a GC content of 99.5%.

[0034] (Example 2)

[0035] The synthetic method of 2,6-difluoroaniline of the present embodiment comprises the following steps:

[0036] ① Add 157.0 g (1.0 mol) of 2,6-difluorobenzamide and 600 mL of methanol into a 1000 mL four-necked flask. After stirring to dissolve, add 79.0 g (0.34 mol) of trichloroisocyanuric acid. A white solid is generated. Keep the reaction at 25 °C for 1 h.

[0037] After the reaction was completed, the solution was filtered, the solvent was removed from the filtrate under reduced pressure, and then dried at 35° C. to obtain 191.0 g of chlorinated product.

[0038] ② Add 561.0 g of 30 wt% potassium hydroxide aqueous solution (containing 3.0 mol of potassium hydroxide) and 191.0 g of the chlorinated product obtained in step ① into a 1500 mL four-necked bottle, stir to dissolve, and then keep warm at 90°C for 3 h.

[0039] After the reaction was completed, the mixture was cooled to 20°C, 500 ml of dichloromethane was added for extraction, and the lower organic layer was separated. After the solvent was removed from the organic layer, 124.1 g of 2,6-difluoroaniline was obtained with a yield of 96.2% and a GC content of 99.7%.

[0040] (Example 3)

[0041] The synthetic method of 2,6-difluoroaniline of the present embodiment comprises the following steps:

[0042] ①Same as Example 1.

[0043] ② Add 200.0 g of 30 wt% sodium hydroxide aqueous solution (containing 1.5 mol of sodium hydroxide) and 95.7 g of the chlorinated product obtained in step ① into a 1000 mL four-necked bottle, stir to dissolve, and then keep warm at 90°C for 3 h.

[0044] After the reaction was completed, the mixture was cooled to 20°C, 250 mL of dichloromethane was added for extraction, and the lower organic layer was separated. After the solvent was removed from the organic layer, 60.5 g of 2,6-difluoroaniline was obtained with a yield of 93.8% and a GC content of 99.4%.

Claims

1. A method for synthesizing 2,6-difluoroaniline, characterized in that The following steps are involved: ① 2,6-difluorobenzamide and trichloroisocyanuric acid are subjected to a first reaction in a first solvent at a first temperature, and then subjected to a first post-treatment to obtain an intermediate; the first temperature is 10-40° C., and the first reaction time is 0.5-3 h; the first post-treatment is suction filtration, and after removing the solvent from the filtrate, drying; the drying temperature is 20-50° C.; ② The intermediate obtained in step ① is subjected to a second reaction in an alkaline solution at a second temperature, and then subjected to a second post-treatment to obtain 2,6-difluoroaniline; the second temperature is 50 to 100° C., and the second reaction time is 2 to 6 hours; the second post-treatment is cooling to room temperature, adding a second solvent for extraction, and removing the solvent from the organic layer after extraction.

2. The method for synthesizing 2,6-difluoroaniline according to claim 1, characterized in that: In the above step ①, the molar ratio of the 2,6-difluorobenzamide to the trichloroisocyanuric acid is 1:0.3 to 1:0.

4.

3. The method for synthesizing 2,6-difluoroaniline according to claim 1, characterized in that: In the above step ①, the first solvent is an alcohol solvent.

4. The method for synthesizing 2,6-difluoroaniline according to claim 1, characterized in that: In the above step ②, the concentration of the alkaline solution is 10wt% to 50wt%, the alkaline solution is a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution, and the molar ratio of the alkali in the alkaline solution to the 2,6-difluorobenzamide in step ① is 2:1 to 5:

1.

5. The method for synthesizing 2,6-difluoroaniline according to claim 1, characterized in that: The second solvent is a halogenated hydrocarbon solvent.