阅读说明：本技术 一种flometoquin的制备方法 (Preparation method of flometoquin ) 是由 杨紫冬 谭悦 田轮 陈三龙 刘林波 于 2021-10-08 设计创作，主要内容包括：一种flometoquin的制备方法,在催化剂的作用下,原料2-乙基-3,7-二甲基-6-(4-(三氟甲氧基)苯氧基)-1,4-二氢喹啉-4-醇在碳酸二甲酯中回流反应,采用气体渗透膜脱除反应产生的甲醇,反应完成后降至室温,水洗,有机相浓缩干燥得到2-乙基-3,7-二甲基-6-(4-(三氟甲氧基)苯氧基)-1,4-二氢喹啉-4-基碳酸甲酯,收率达96.7%,产品含量达99.2%(液谱外标)。该制备方法具有工艺简单、无需蒸馏、产品纯度和收率高等优点。(A preparation method of flometoquin comprises the steps of carrying out reflux reaction on raw material 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-alcohol in dimethyl carbonate under the action of a catalyst, removing methanol generated in the reaction by using a gas permeable membrane, cooling to room temperature after the reaction is finished, washing with water, concentrating and drying an organic phase to obtain 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-yl methyl carbonate, wherein the yield is 96.7%, and the product content is 99.2% (liquid spectrum external standard). The preparation method has the advantages of simple process, no need of distillation, high product purity and yield, and the like.)

1. A preparation method of flometoquin is characterized by comprising the following steps: under the action of a catalyst, 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-alcohol performs reflux reaction in dimethyl carbonate, a separator provided with an A-type molecular sieve pervaporation inorganic membrane is adopted to remove methanol generated by the reaction, the temperature is reduced to room temperature after the reaction is finished, the mixture is washed with water for layering, and an organic phase is concentrated and dried to obtain 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-yl methyl carbonate, wherein the reaction formula is as follows:。

2. a method of preparing flometoquin, as claimed in claim 1, wherein: the mass ratio of the 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-alcohol to the dimethyl carbonate is 1: 2.0-5.0.

3. A method of preparing flometoquin, as claimed in claim 1, wherein: the reaction is carried out at normal pressure, and the reaction temperature is the reflux temperature of the solvent.

4. A method of preparing flometoquin, as claimed in claim 1, wherein: the catalyst used in the reaction is one of sodium tert-butoxide, potassium tert-butoxide and sodium ethoxide, and the dosage of the catalyst is 4-6% of the mass of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-ol.

5. A method of preparing flometoquin, as claimed in claim 1, wherein: a separator provided with an A-type molecular sieve pervaporation inorganic membrane is adopted, methanol and water in organic vapor can permeate the membrane and then are removed out of the system through condensation, and dimethyl carbonate cannot permeate the membrane and returns to the reaction kettle through condensation.

Technical Field

The invention relates to a preparation method of flometoquin. More particularly, the present invention relates to an improved and simplified process for the preparation of flometoquin.

Background

Flometoquin is a novel quinoline pesticide developed by Nippon Mingmingji and Nippon Chemicals, has a novel action mechanism, and can be used for controlling pests resistant to existing pesticides. The pesticide has excellent control effect on thysanoptera pests (thrips), whiteflies, galls and small lepidoptera pests, and has the advantages of high killing speed and long lasting period.

"Synthesis of novel quinoline pesticide Flometoquin", Liu' an Chang, Bao Yang, Huang Shi, Li Qi, Deng III, Wuhan project university newspaper, No. 3, volume 41, page 238-, under the action of potassium tert-butoxide, 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) quinoline-4-ol reacts with methyl chloroformate in N, N-Dimethylacetamide (DMAC), ice water is added for solid precipitation after the reaction is finished, the solid is recrystallized by normal hexane and dried to obtain Flometsoquin white solid powder, the method has the advantages of high toxicity, flammability and corrosivity of methyl chloroformate, high price of raw materials, more three wastes, recrystallization of solid, complex post-treatment, solvent recovery, high production cost, yield of 90.8 percent and purity of 94.8 percent.

"the synthesis and biological activity research of Flometoquin as pesticide", Liwei, Liu Yi Ping, Gao De Liang, Huli, Pi Bai, Wan Er Long, Xue Song, Wu Dao Xin, Huang Ming Zhi, fine chemical intermediate, No. 1, No. 46, pages 27-29, 2016 years 2 months, tetrahydrofuran as solvent, in an amount of 55.4 times of the mass of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-ol as raw material, reacting with methyl chloroformate under the action of sodium hydride to remove part of tetrahydrofuran, adding into water, extracting with ethyl acetate for 2 times, drying with anhydrous sodium sulfate, concentrating under reduced pressure to remove ethyl acetate, and separating by column chromatography to obtain the product, which has expensive raw material, large solvent consumption and high recovery cost, the post-treatment is complicated, the production treatment cost is high, the purity is 95 percent, and the yield is 20.6 percent.

The gas permeable membrane technology is a new membrane separation technology, which separates, fractionates, purifies and enriches multi-component mixtures (gases or liquids) under the action of external energy or chemical potential difference by means of selective permeation of membranes. Macroscopically, membrane separation is similar to "filtration," but microscopically, it is not as simple as filtration, which allows small molecules to permeate through the micropores of a filtration membrane, but rather involves adsorption of molecules on the membrane, dissolution and diffusion in the membrane, as the molecules of the substance permeate through the polymer membrane. Gas molecules are first adsorbed on the outer surface of the membrane and dissolve in the membrane, then permeate the membrane, desorb and diffuse on the other surface of the membrane. Because the components of the mixture have different binding capacities with the membrane, the dissolution and diffusion rates of the components in the membrane are different, which is the selectivity of the membrane separation. The gas membrane separation is to separate gas by means of the selective permeation of the membrane with the gas pressure as driving force. The current industrialized gas membrane separation technology has high permeation rate and good permeation selectivity, and the mechanical strength, excellent thermal stability and chemical stability of the technology meet the requirements of chemical synthesis.

Disclosure of Invention

The invention mainly aims to provide an improved method for preparing 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-methyl carbonate, which overcomes the problems of the prior art that a large amount of toxic, harmful and expensive raw materials are used, the post-treatment is complicated, the recovery amount of a solvent is large, a large amount of waste water is generated, and the like, and provides a preparation method of flometoquin, which has the advantages of simple process, no need of recrystallization, low production cost, high product purity and high yield. The technical scheme adopted by the invention for solving the technical problems is as follows: under the action of a catalyst, 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-alcohol is subjected to reflux reaction in dimethyl carbonate, a separator provided with an A-type molecular sieve pervaporation inorganic membrane is adopted to remove methanol generated by the reaction and trace water in a system, the temperature is reduced to room temperature after the reaction is finished, the mixture is washed with water for delamination, and an organic phase is concentrated and dried to obtain 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-yl methyl carbonate.

Further, the mass ratio of the 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinoline-4-ol to dimethyl carbonate in the reaction is 1: 2.0-5.0.

Further, the above reaction is carried out under normal pressure, and the reaction temperature is the reflux temperature of the solvent.

Furthermore, the catalyst used in the reaction is one of sodium tert-butoxide, potassium tert-butoxide and sodium ethoxide, and the dosage of the catalyst is 4-6% of the mass of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol.

Furthermore, the reaction adopts a separator provided with an A-type molecular sieve pervaporation inorganic membrane, methanol and water in organic vapor can permeate the membrane and then are removed out of the system through condensation, and a solvent cannot permeate the membrane and returns to the reaction kettle through a condenser.

The reaction formula is as follows:

compared with the prior art, the scheme has the advantages that:

1. the scheme adopts the gas permeation membrane separator to remove methanol generated by reaction and trace water in a system in the reaction process, further enables the reaction balance to move to the right, improves the conversion rate of the reaction, simultaneously inhibits the side reaction of raw materials, products and water, has very low impurity content in the product, and improves the yield and purity of the product.

2. The solvent is recovered without distilling off methanol, and the usage amount of the solvent and the loss amount of the solvent are reduced. The preparation method has the advantages of simple process, no need of secondary distillation for solvent recovery, high product purity and yield, and the like.

3. Under the action of the catalyst, the reaction speed is accelerated, the reaction time is shortened, and the effects of energy conservation and consumption reduction are achieved.

4. Methyl carbonate is used as a raw material and a solvent instead of methyl chloroformate, so that the method is safer and more environment-friendly, has good environment-friendly benefits in actual production, and ensures safer production.

5. Simplifies the post-treatment operation, simplifies the operation, does not need recrystallization and a large amount of solvent extraction, and reduces the post-treatment cost.

Detailed Description

The invention is further described with reference to the following examples, but the scope of the invention is not limited thereby.

Example 1:

30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 60.0 g of dimethyl carbonate and 1.2 g of sodium tert-butoxide are added into a 250 mL three-neck flask, the flask is connected with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, the mixture is stirred and heated to reflux, the temperature is kept for reaction for 4.0 h, a mixture of methanol and water in organic vapor permeates an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, a system is separated, and a solvent is condensed and reflows to a kettle for reaction. At the end of the reaction, a total of 2.6 g of methanol and water were collected. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 33.1 g of a white solid having a content of 98.9% (external standard of liquid spectrum) and a yield of 95.4% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

Example 2:

adding 30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 150.0 g of dimethyl carbonate and 1.8 g of sodium tert-butoxide into a 250 mL three-neck flask, connecting the flask with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, stirring and heating to reflux, carrying out heat preservation reaction for 4.0 h, allowing a mixture of methanol and water in organic vapor to permeate an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, separating out a system, and condensing a solvent and refluxing to a kettle for reaction. At the end of the reaction, 3.8 g of methanol and water were collected together. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 33.4 g of a white solid with a content of 99.2% (liquid chromatography external standard) and a yield of 96.7% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

Example 3:

30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 90.0 g of dimethyl carbonate and 1.8 g of sodium tert-butoxide are added into a 250 mL three-neck flask, the flask is connected with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, the mixture is stirred and heated to reflux, the temperature is kept for reaction for 4.0 h, a mixture of methanol and water in organic vapor permeates an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, a system is separated, and a solvent is condensed and reflows to a kettle for reaction. At the end of the reaction, a total of 2.7 g of methanol and water were collected. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 33.5g of a white solid having a content of 98.8% (liquid spectrum external standard) and a yield of 96.5% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

Example 4:

30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 90.0 g of dimethyl carbonate and 1.2 g of potassium tert-butoxide are added into a 250 mL three-neck flask, the flask is connected with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, the mixture is stirred and heated to reflux, the temperature is kept for reaction for 4.0 h, a mixture of methanol and water in organic vapor permeates an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, a system is separated, and a solvent is condensed and reflows to a kettle for reaction. At the end of the reaction, 3.3 g of methanol and water were collected together. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 33.1 g of a white solid having a content of 98.6% (liquid spectrum external standard) and a yield of 95.1% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

Example 5:

30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 60.0 g of dimethyl carbonate and 1.5 g of sodium ethoxide are added into a 250 mL three-neck flask, the flask is connected with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, stirring and heating are carried out until reflux, the temperature is preserved for reaction for 4 h, a mixture of methanol and water in organic vapor permeates an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, a system is separated, and a solvent is condensed and reflows to a kettle for reaction. At the end of the reaction, a total of 2.5 g of methanol and water were collected. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 33.4 g of a white solid having a content of 98.1% (external standard of liquid spectrum) and a yield of 94.9% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

Example 6:

30.0 g of 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol (0.079 mol), 90.0 g of dimethyl carbonate and 1.5 g of sodium ethoxide are added into a 250 mL three-neck flask, the flask is connected with an inlet of an A-type molecular sieve pervaporation inorganic membrane device, stirring and heating are carried out until reflux, the temperature is preserved for reaction for 4 h, a mixture of methanol and water in organic vapor permeates an A-type molecular sieve pervaporation inorganic membrane tube in the reaction process, a system is separated, and a solvent is condensed and reflows to a kettle for reaction. At the end of the reaction, a total of 2.9 g of methanol and water were collected. The reaction mixture was cooled to room temperature, washed with water once, and the organic phase was concentrated and dried to give 32.9 g of a white solid having a content of 98.4% (external standard of liquid spectrum) and a yield of 94.3% (based on 2-ethyl-3, 7-dimethyl-6- (4- (trifluoromethoxy) phenoxy) -1, 4-dihydroquinolin-4-ol).

The foregoing is considered as illustrative of the preferred embodiments of the invention and is not to be construed as limiting the invention in any way. Although the present invention has been described with reference to the preferred embodiments, it is not intended to be limited thereto. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical spirit of the present invention should fall within the protection scope of the technical scheme of the present invention, unless the technical spirit of the present invention departs from the content of the technical scheme of the present invention.