Method for preparing nicosulfuron

Abstract

The invention discloses a method for preparing nicosulfuron. According to the method, a micro-channel reactor is used, a new solvent and material ratio is adopted, the mass transfer efficiency is improved, and high reaction rate and high yield are achieved. The process comprises the following steps: step 1, setting the temperature of the micro-channel reactor to be a preset temperature, and pumping a reaction solvent into the micro-channel reactor by using a diaphragm pump after the preset temperature is reached; 2, uniformly mixing pyrilamine, phenyl ester and the reaction solvent, pumping the mixed solution into the tubular reactor by using a diaphragm pump, and stopping adding the reaction solvent; and 3, carrying out rotary evaporation on the reacted mixed solvent, washing, filtering and drying to obtain a nicosulfuron finished product. By adopting the micro-channel reactor, the problem of long six-step condensation time (8-10 hours) of the traditional nicosulfuron is solved, the energy cost is reduced, the process time is shortened, side reactions are reduced, and the product purity is improved.

Description

Technical Field

[0001] The invention belongs to the field of industrial synthesis technology, and specifically relates to a method for preparing nicosulfuron. The preparation method uses pyrimidine amine and phenyl ester as raw materials to prepare nicosulfuron. Background Art

[0002] Nicosulfuron, chemically known as 2-(4,6-dimethoxypyrimidin-2-ylcarbamoylaminosulfonyl)-N,N-dimethylnicotinamide (English name Nicosulfuron), is a cornfield sulfonylurea herbicide variety discovered by Ishihara Sangyo Co., Ltd. in the mid-1980s. High-purity Nicosulfuron can ensure its safety and effectiveness during application and avoid adverse effects on the environment or crops. In addition, the purity of Nicosulfuron also directly affects its ratio with other ingredients, thereby affecting the overall performance and effect of the preparation. Therefore, maintaining the purity of Nicosulfuron is crucial to ensuring its performance as a herbicide.

[0003] At present, there are mainly three routes for the production of nicosulfuron: the amine ester route, the light-fixing route and the phenyl ester route. The phenyl ester route avoids the use of highly toxic and highly polluting raw materials, such as phosgene or ethyl chloroformate, thereby reducing the discharge of three wastes and improving the reaction selectivity. However, in the phenyl ester process, the condensation reaction and heat preservation time of the intermediate phenyl ester and pyrimidine amine are relatively long (8-10h), and the purity of the obtained nicosulfuron product is generally ≥95%.

[0004] Therefore, the current industry is in urgent need of finding a new method for synthesizing nicosulfuron with simple operation steps and short reaction time.

[0005] . Summary of the invention

[0006] In order to achieve the above-mentioned invention object, the technical solution of the present invention is: A method for preparing nicosulfuron comprises the following steps: Step 1, the microchannel reactor is set to a predetermined temperature, and after reaching the predetermined temperature, the reaction solvent is pumped into the microchannel reactor using a diaphragm pump; Step 2: After the pyrimidine amine, phenyl ester and reaction solvent are uniformly mixed, the mixed solution is pumped into the microchannel reactor using a diaphragm pump, and the addition of the reaction solvent is stopped; Step 3: After the reaction is completed, the mixed solvent is subjected to rotary evaporation, washed, filtered and dried to obtain a nicosulfuron finished product.

[0007] The predetermined temperature of step 1 is 70-120°C.

[0008] The solvent is selected from any one of toluene, DMF and dichloroethane. A certain amount of the reaction solvent is maintained in the entire microchannel.

[0009] In the step 1, nitrogen is introduced at a flow rate of 10 to 50 mL / min. The nitrogen is introduced in advance in the reaction solvent in the form of bubbles and achieves a uniform and orderly disturbance state. After the raw material mixture enters, the contact of the materials in the microchannel is promoted, thereby accelerating the reaction.

[0010] In the microchannel reactor of the present invention, when the gas flow rate in the system is too small, it will not disturb the reaction liquid; while when the gas volume is too large, the gas and liquid will be stratified, the gas will no longer exist in the form of bubbles, and the effect of enhancing mass transfer will be reduced. When the temperature and gas flow conditions are set in advance, the optimal reaction conditions can be achieved when the raw materials enter the reactor. The high reaction rate brought by the preheating temperature and the turbulent disturbance brought by the correct gas-liquid-solid three-phase ratio accelerate the mass transfer rate, thereby greatly reducing the reaction time.

[0011] The molar ratio of the phenyl ester to the pyrimidine amine is 1:1 to 1:3; and the solid-liquid mass ratio in the mixed solution is 4:10 to 4:100.

[0012] The mixed solution is pumped into the microchannel reactor at a flow rate of 5-20 mL / min, and reacts under this flow condition. After the reaction is completed, the material is discharged from the end of the microchannel.

[0013] Beneficial effects of the present invention: The present invention uses Corning microchannel G1 glass reactor (heart-shaped) with large specific surface area, fast mass transfer and heat transfer rate, and can reduce the synthesis reaction time of Nicosulfuron. Because the microchannel reactor is a kind of plug flow reactor, it reduces the contact between raw materials and products, inhibits the occurrence of side reactions, reduces impurities, and subsequent reactions can ensure higher yields and purity. In summary, compared with the key step condensation reaction of Nicosulfuron synthesis by the traditional phenyl ester method, the present invention has the advantages of short reaction time, ending the reaction process when the entire microchannel reactor is ended, the reaction time is 5-20 minutes, reducing the reaction solvent, continuous feeding operation, great industrial application value, and reducing time and energy costs.

[0014] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0015] The preparation method of Nicosulfuron in the present invention is mainly achieved by the following steps: Example 1: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 325.1 g of the product was obtained, with a yield of 79.5% and a liquid phase purity of 97.9%.

[0016] Example 2: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor is set to 80°C, and the flow rate of the reaction solvent of the diaphragm pump is set to 10 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% is taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate are stable, the reaction solvent is stopped, and the mixed solution is passed into the microchannel reactor at 10 mL / min. After the reaction is completed, the solvent is removed by vacuum distillation, washed and dried, and 270 g of the product is obtained, with a yield of 66.6% and a liquid phase purity of 90.5%.

[0017] Example 3: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 60 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 295.2 g of the product was obtained, with a yield of 72.1% and a liquid phase purity of 92.9%.

[0018] Example 4: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor is set to 120°C, the flow rate of the diaphragm pump reaction solvent is set to 10 mL / min, and the flow rate of nitrogen gas is set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% is taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and gas-liquid flow rate are stable, the reaction solvent is stopped, and the mixed solution is passed into the microchannel reactor at 10 mL / min. After the reaction is completed, the solvent is removed by vacuum distillation, washed and dried, and 348.5 g of the product is obtained, with a yield of 85.2% and a purity of 98.2%.

[0019] Example 5: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 186.96 g (1.2 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 335.7 g of the product was obtained, with a yield of 68.2% and a liquid phase purity of 98.6%.

[0020] Example 6: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 311.6 g (2 mol) of pyrimidine amine and 7790 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 330.1 g of the product was obtained, with a yield of 40.2% and a liquid phase purity of 96.6%.

[0021] Example 7: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 12464 mL of toluene and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 332.8 g of the product was obtained, with a yield of 81.2% and a liquid phase purity of 98.2%.

[0022] Example 8: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of DMF and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 328.1 g of the product was obtained, with a yield of 80.4% and a liquid phase purity of 98.7%.

[0023] Example 9: Preparation of Nicosulfuron Steps: The temperature of the microchannel reactor was set to 80°C, the flow rate of the diaphragm pump reaction solvent was set to 10 mL / min, and the flow rate of nitrogen gas was set to 20 mL / min; 425 g (1 mol) of phenyl ester with a purity of 82% was taken, mixed with 155.8 g (1 mol) of pyrimidine amine and 7790 mL of dichloroethane and stirred evenly. When the reactor temperature and the gas-liquid flow rate were stable, the reaction solvent was stopped, and the mixed solution was passed into the microchannel reactor at 10 mL / min. After the reaction was completed, the solvent was removed by vacuum distillation, washed and dried, and 316.9 g of the product was obtained, with a yield of 77.3% and a liquid phase purity of 97.7%.

Claims

1. A method for preparing nicosulfuron, characterized in that: The following steps are involved: Step 1, the microchannel reactor is set to a predetermined temperature. After reaching the predetermined temperature, the reaction solvent is pumped into the microchannel reactor using a diaphragm pump, and nitrogen is introduced into the reactor at the same time; Step 2: After the pyrimidine amine, phenyl ester and reaction solvent are uniformly mixed, the mixed solution is pumped into the microchannel reactor using a diaphragm pump, and the addition of the reaction solvent is stopped; Step 3: After the reaction is completed, the mixed solvent is subjected to rotary evaporation, washed, filtered and dried to obtain a nicosulfuron finished product.

2. The method for preparing nicosulfuron according to claim 1, characterized in that: The predetermined temperature of step 1 is 70-120°C.

3. The method for preparing Nicosulfuron according to claim 1, characterized in that: The solvent in step 1 is selected from any one of toluene, DMF and dichloroethane.

4. The method for preparing Nicosulfuron according to claim 1, characterized in that: In the step 1, the nitrogen inlet flow rate is 10 to 50 mL / min.

5. The method for preparing Nicosulfuron according to claim 1, characterized in that: The molar ratio of the phenyl ester to the pyrimidine amine is 1:1 to 1:3; and the solid-liquid mass ratio in the mixed solution is 4:10 to 4:

100.

6. The method for preparing Nicosulfuron according to claim 1, characterized in that: The mixed solution is pumped into the microchannel reactor at a flow rate of 5-20 mL / min.