阅读说明：本技术 一种n-甲基邻氟苯胺的合成方法 (Synthesis method of N-methyl o-fluoroaniline ) 是由 张璞 王豪 吴耀军 陈文新 张烽 侯远昌 于 2020-11-11 设计创作，主要内容包括：本发明涉及属于农药、医药中间体制备领域,尤其涉及一种N-甲基邻氟苯胺制备方法,包括如下步骤：以邻氟苯胺为原料,以碳酸二甲酯为反应原料及反应溶剂,在碱性催化剂作用下保温反应；反应结束后过滤除去催化剂,滤液经精馏分离,将溶剂碳酸二甲酯、与产物分离。与现有技术相比,本发明具有以下有效效果：本发明提供的N-甲基邻氟苯胺新的合成方法,仅需一步反应,选择性极高,产品质量好,选用的甲基化试剂碳酸二甲酯低毒绿色安全,三废产出低,是一种极具竞争力的“绿色”化学工艺。(The invention belongs to the field of preparation of pesticides and medical intermediates, and particularly relates to a preparation method of N-methyl o-fluoroaniline, which comprises the following steps: performing heat preservation reaction on o-fluoroaniline serving as a raw material, dimethyl carbonate serving as a reaction raw material and a reaction solvent under the action of an alkaline catalyst; after the reaction is finished, the catalyst is removed by filtration, and the filtrate is separated by rectification to separate the solvent dimethyl carbonate from the product. Compared with the prior art, the invention has the following effective effects: the new synthesis method of the N-methyl o-fluoroaniline provided by the invention only needs one-step reaction, has extremely high selectivity and good product quality, the selected methylating reagent dimethyl carbonate is low in toxicity, green and safe, the three wastes are low in yield, and the synthesis method is an extremely competitive green chemical process.)

1. A synthetic method of N-methyl o-fluoroaniline is characterized by comprising the following steps:

taking o-fluoroaniline as a raw material, taking dimethyl carbonate as a reaction raw material and a reaction solvent, adding an alkaline catalyst, carrying out heat preservation reaction, filtering to remove the catalyst after the reaction is finished, rectifying the filtrate to remove the solvent, and purifying to obtain N-methyl o-fluoroaniline;

the reaction formula of the above reaction is as follows:

2. the method for synthesizing N-methyl-o-fluoroaniline according to claim 1, wherein the basic catalyst comprises basic montmorillonite, basic kaolin, basic zeolite, basic molecular sieve or the like.

3. The method for synthesizing N-methyl-o-fluoroaniline according to claim 1, wherein the mass of the basic catalyst added is 0.1% to 30% of the mass of o-fluoroaniline.

4. The method for synthesizing N-methyl o-fluoroaniline according to claim 3, wherein the mass of the basic catalyst added is 0.5 to 20% of the mass of the o-fluoroaniline.

5. The method for synthesizing N-methyl o-fluoroaniline according to claim 4, wherein the mass of the basic catalyst added is 5 to 15% of the mass of the o-fluoroaniline.

6. The method for synthesizing N-methyl o-fluoroaniline according to claim 1, wherein the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1: 0.8-20.

7. The method for synthesizing N-methyl o-fluoroaniline according to claim 6, wherein the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1:2 to 20.

8. The method for synthesizing N-methyl-o-fluoroaniline according to claim 1, wherein the temperature of the heat-preservation reaction is 80-120 ℃.

9. The method for synthesizing N-methyl-o-fluoroaniline according to claim 1, characterized in that the catalyst obtained after filtration is subjected to activation treatment with an inorganic base, washed with water, dried and recycled; the number of times of recycling the catalyst is 25-50.

10. The method for synthesizing N-methyl-o-fluoroaniline according to claim 9, wherein the catalyst obtained after filtration is reacted for 1 to 24 hours in an aqueous solution of sodium hydroxide with a mass concentration of 5 to 40% with stirring, washed with water, dried at 80 to 120 ℃ for 2 to 10 hours, and then recycled.

Technical Field

The invention belongs to the field of preparation of pesticides and medical intermediates, and particularly relates to a synthesis method of N-methyl o-fluoroaniline.

Background

The N-methyl o-fluoroaniline belongs to fluorine-containing N-alkyl arylamine, is a very important organic raw material and fine chemical intermediate, and is widely applied to the fields of fuel, plastics, medicines, pesticides and the like. With the continuous development of dye and rubber industries, the dosage of pesticides and medicines is continuously increased, the demand of N-methyl o-fluoroaniline is rapidly increased, and the corresponding synthesis development is concerned.

In particular, the synthesis method of N-methyl o-fluoroaniline is various, and can be divided into the following methods according to different reaction routes:

patent No. CN107973721A discloses a method for preparing N-methyl o-fluoroaniline by using o-fluoroaniline as a raw material, adding toluene, paraformaldehyde and a catalyst A, carrying out heat preservation reaction, then dehydrating, carrying out condensation reaction, then carrying out treatment to obtain N-methylene o-fluoroaniline, carrying out hydrogenation reaction, and carrying out post-treatment to obtain N-methyl o-fluoroaniline. However, imine in the first step of the method is mainly in a trimerization form, a large amount of N, N-dimethyl o-fluoroaniline is generated as a byproduct in the reduction stage, and the intermediate needs to be rectified and purified in the later stage, but the purification is difficult, so that the purity and the yield of the intermediate are low. And further hydrogenation reaction is needed, so that the industrial production has certain problems.

② the Catalysis scienen & Technology,6(22)),795-796 discloses a method for preparing N-methyl o-fluoroaniline by methylation reaction of o-fluoroaniline as raw material and dimethyl carbonate. However, since dimethyl carbonate is a raw material which is relatively easy to methylate, dimethyl-substituted N, N-dimethyl-o-fluoroaniline is actually partially (84%) produced, and the target product, N-methyl-o-fluoroaniline, is only about 5%.

③ (organics, 14, 15),3948-3951, 2012) discloses a method for preparing N-methyl o-fluoroaniline by methylation reaction of o-fluoroaniline as a starting material and tetrahydrofuran as a solvent with dimethyl sulfate under the catalysis of N-butyllithium. The method needs to be carried out at a low temperature of minus 78 ℃, the conditions are harsh, dimethyl sulfate is a class 6.1 class A organic hypertoxic, and n-butyl lithium needs to be anhydrous and anaerobic in use, so that the potential safety hazard is large.

Document (Journal of Agricultural and Food Chemistry,58(23), 12357-12365; 2010) discloses a method for preparing N-methyl o-fluoroaniline by methylation reaction of o-fluoroaniline serving as a starting material and methyl iodide in the presence of sodium hydride as a catalyst and DMF serving as a solvent. However, the method is also unsafe in use of sodium hydride, expensive in methyl iodide, high in raw material cost and difficult in industrial application.

CN109053486A discloses a method for preparing N-methyl o-fluoroaniline by diazotizing o-fluoroaniline which is used as a raw material, and then reacting the o-fluoroaniline with a methylamine aqueous solution at high temperature and high pressure. The method relates to diazotization reaction, a large amount of concentrated hydrochloric acid is adopted, the temperature requirement is extremely strict between 15 ℃ below zero and 10 ℃ below zero, once the reaction temperature is too high, a large amount of organic tar is generated, a large amount of acidic wastewater is generated, the intermediate is not easy to store, and the yield and the quality of the next methylamine amination product are directly influenced.

The five routes all belong to methylation reaction, but have a common defect that the selectivity is poor, and the content of the by-product N, N-dimethyl o-fluoroaniline is high, so that the separation is difficult or the product quality is poor. Therefore, a process scheme capable of providing high selectivity for the synthesis of N-methyl o-fluoroaniline is urgently needed.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: provides a high-efficiency green environment-friendly N-methyl o-fluoroaniline synthesis process with high selectivity.

In a first aspect of the invention, a method for synthesizing N-methyl o-fluoroaniline is provided, which comprises the following steps:

taking o-fluoroaniline as a raw material, dimethyl carbonate as a reaction raw material and a reaction solvent, adding an alkaline catalyst, carrying out heat preservation reaction, filtering to remove the catalyst after the reaction is finished, and rectifying and purifying the filtrate to obtain N-methyl o-fluoroaniline;

the reaction formula of the above reaction is as follows:

preferably, the basic catalyst comprises basic montmorillonite, basic kaolin, basic zeolite, basic molecular sieve and the like. Further, the molecular sieve is selected from the group consisting of alkali montmorillonite, alkali kaolin, and alkali molecular sieves.

Preferably, the adding mass of the basic catalyst is 0.1-30% of the mass of the o-fluoroaniline; further, the adding mass of the alkaline catalyst is 0.5-20% of the mass of the o-fluoroaniline; furthermore, the adding mass of the basic catalyst is 5-10% of the mass of the o-fluoroaniline.

Preferably, the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1: 0.8-20; further, the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1: 2-20; furthermore, the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1: 2-7; in a preferred embodiment of the invention, the mass ratio of the o-fluoroaniline to the dimethyl carbonate is 1:2 to 5.

Preferably, the temperature of the heat preservation reaction is 80-120 ℃, and the heat preservation time is 5-15 hours; the reaction can be carried out under normal pressure or in a pressurized reaction kettle; the reaction temperature is 50-120 ℃, the pressure is 5-15 kg, and the reaction time is 5-10 hours.

Preferably, the catalyst obtained by filtering is activated by inorganic base treatment, washed by water and dried, and then recycled; furthermore, the recycling frequency of the filtered catalyst is 25-50 times. Further, the catalyst obtained by filtering is stirred and heated to 50-99 ℃ in a sodium hydroxide aqueous solution with the mass concentration of 5-40%, the reaction is carried out for 1-24 h, and the catalyst is washed by water, dried for 2-10 h at 80-120 ℃ and recycled. Furthermore, a sodium hydroxide solution with a mass concentration of 25% is used, the reaction temperature is 95 ℃, and the reaction time is 4 hours.

Compared with the prior art, the invention has the following beneficial effects: the new synthesis method of the N-methyl o-fluoroaniline provided by the invention only needs one-step reaction, has extremely high selectivity and good product quality, the selected methylating reagent dimethyl carbonate is low in toxicity, green and safe, the three wastes are low in yield, and the synthesis method is an extremely competitive green chemical process.

Drawings

FIG. 1 is a hydrogen spectrum of N-methyl o-fluoroaniline synthesized in an embodiment of the invention.

Detailed Description

The invention is illustrated but not limited by the following examples. The technical solutions protected by the present invention are all the simple replacements or modifications made by the skilled person in the art.

Example 1:

100g of dimethyl carbonate, 15g (0.1351mol) of o-fluoroaniline and 0.75g of catalyst basic montmorillonite are added into a 250ml reaction bottle, stirred and heated under normal pressure until reflux is reached, and the reflux time is 10-15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by a rectifying column of 20-30 cm, and collecting main fraction at 85-88 ℃ to obtain 16.03g of N-methyl o-fluoroaniline, wherein the GC purity is 98.79%, the yield is 96.89% after rectification, and the by-product N, N-dimethyl o-fluoroaniline is 0.21%.

Example 2:

100g of dimethyl carbonate, 15g (0.1351mol) of o-fluoroaniline and 1.5g of catalyst basic montmorillonite are added into a 250ml reaction bottle, stirred and heated under normal pressure until reflux is reached, and the reflux time is 10-15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure through a rectifying column of 20-30 cm, and collecting main fractions at 85-88 ℃ to obtain 16.21g of N-methyl o-fluoroaniline, wherein the GC purity is 98.95%, the yield after rectification is 97.97%, and the by-product N, N-dimethyl o-fluoroaniline is 0.15%.

Example 3:

100g of dimethyl carbonate, 15g (0.1351mol) of o-fluoroaniline and 1.00g of catalyst basic kaolin are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 10-15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure through a rectifying column of 20-30 cm, and collecting main fractions at 85-88 ℃ to obtain 16.59g of N-methyl o-fluoroaniline, wherein the GC purity is 98.53%, the yield after rectification is 96.2%, and the by-product N, N-dimethyl o-fluoroaniline is 1.17%.

Example 4:

150g of dimethyl carbonate, 15g (0.1351mol) of o-fluoroaniline and 1.5g of catalyst basic kaolin are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 10-15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by a rectifying column of 20-30 cm, and collecting main fraction at 85-88 ℃ to obtain 16.64g of N-methyl o-fluoroaniline, wherein the GC purity is 97.23%, the yield after rectification is 95.5%, and the by-product N, N-dimethyl o-fluoroaniline is 2.17%.

Example 5:

225g of dimethyl carbonate, 15g (0.0.1351mol) of o-fluoroaniline and 0.75g of catalyst basic molecular sieve NaY are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 10 to 15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by a rectifying column of 20-30 cm, and collecting main fraction at 85-88 ℃ to obtain 16.67g of N-methyl o-fluoroaniline, wherein the GC purity is 98.92%, the yield is 97.5% after rectification, and the by-product N, N-dimethyl o-fluoroaniline is 0.30%.

Example 6:

105g of dimethyl carbonate, 15g (0.0.1351mol) of o-fluoroaniline and 1.5g of catalyst basic molecular sieve NaY are added into a 250ml reaction bottle, and the mixture is stirred under normal pressure and heated to reflux for 11 to 12 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, and rectifying the filtrate by a 20-30 cm rectifying column at normal pressure to remove the solvent to the full extent to obtain 16.79g of N-methyl o-fluoroaniline, wherein the GC purity is 99.2%, the yield is 99.4% after rectification, and the by-product N, N-dimethyl o-fluoroaniline is 0.29%.

Example 7:

the catalyst alkaline molecular sieve NaY after being recycled and reused for 25 times is activated and catalyzed, and is reacted for 4 hours at the temperature of 95 ℃ in 25% sodium hydroxide and alkaline water, then cooled to 20 ℃ and filtered, and the wet product is dried for 4 hours in a drying oven at the temperature of 100 ℃ after being washed by a proper amount of water, and the water content is less than or equal to 0.05%, and the catalyst is recycled. The specific experimental conditions were as follows:

105g of dimethyl carbonate, 15g (0.0.1351mol) of o-fluoroaniline and 1.5g of activated catalyst basic molecular sieve NaY are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 10 to 15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the materials to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by using a 20-30 cm rectifying column, removing the solvent to the full extent, cooling the materials to obtain 16.74g of N-methyl o-fluoroaniline, wherein the GC purity is 99.12%, the yield is 99.1% after rectification, and the by-product N, N-dimethyl o-fluoroaniline is 0.32%.

The products of the examples of the invention were confirmed by hydrogen and mass spectrometry.

While only the preferred embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.