阅读说明：本技术 一种n-苯基双（三氟甲磺酰）亚胺的制备方法 (Preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide ) 是由 花莹曦 王巍 吕灵华 张建伟 倪珊珊 郝春辉 张琴 朱姜涛 于 2020-12-30 设计创作，主要内容包括：本发明提供一种N-苯基双(三氟甲磺酰)亚胺的制备方法,其包括如下步骤：将三氟甲磺酸与二氯亚砜反应生产三氟甲磺酰氯；将苯胺溶解在溶剂中,加入三乙胺等有机碱作为缚酸剂,再滴加三氟甲磺酰氯,制备得到N-苯基双(三氟甲磺酰)亚胺。本方案的原料廉价易得；三氟甲磺酰氯参与反应基团利用率高,反应高效；无需低温或带压等特殊装置,易操作；基本无固体三废产生。(The invention provides a preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide, which comprises the following steps: reacting trifluoromethanesulfonic acid with thionyl chloride to produce trifluoromethanesulfonyl chloride; dissolving aniline in a solvent, adding organic base such as triethylamine and the like as an acid-binding agent, and then dropwise adding trifluoromethanesulfonyl chloride to prepare N-phenyl bis (trifluoromethanesulfonyl) imine. The raw materials of the scheme are cheap and easy to obtain; the utilization rate of the trifluoromethane sulfonyl chloride participating in the reaction group is high, and the reaction is efficient; special devices such as low temperature or pressure are not needed, and the operation is easy; basically no solid three wastes are generated.)

1. A preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide is characterized in that: preparing trifluoromethanesulfonic acid chloride by using trifluoromethanesulfonic acid as a raw material; dissolving aniline in a solvent, and reacting the aniline with organic base serving as an acid-binding agent; then adding the obtained trifluoromethanesulfonyl chloride to react to obtain N-phenyl bis (trifluoromethanesulfonyl) imide.

2. The preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide according to claim 1, characterized by comprising the following specific steps:

step one, slowly adding thionyl chloride into trifluoromethanesulfonic acid, then adding a catalyst N, N-dimethylformamide, and stirring at 40-50 ℃ for 4-12 hours to prepare a crude trifluoromethanesulfonyl chloride product;

step two, distilling the crude product of the trifluoromethanesulfonyl chloride under reduced pressure, and removing excessive thionyl chloride and N, N-dimethylformamide serving as a catalyst to obtain a pure product of the trifluoromethanesulfonyl chloride;

step three, dissolving aniline in a solvent, adding organic alkali serving as an acid-binding agent, and slowly dropwise adding the trifluoromethanesulfonyl chloride pure product obtained in the step two under ice bath to obtain a crude product of N-phenyl bis (trifluoromethanesulfonyl) imide;

distilling to remove the solvent, washing with water, and recrystallizing with alcohol to obtain N-phenyl bis (trifluoromethanesulfonyl) imide;

the molar ratio of trifluoromethanesulfonic acid to thionyl chloride was 1: 4-10;

the molar ratio of triflic acid to catalyst was 1: 0.01 to 0.1;

the molar ratio of the trifluoromethanesulfonyl chloride to the aniline is 2.1-4: 1;

the molar ratio of the organic base to the aniline is 2-4: 1.

3. the process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 1 or 2, characterized in that: the organic base is one or more of triethylamine, N-diisopropylethylamine, triethylene diamine and hexamethylene tetramine.

4. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 3, characterized in that: the organic base is triethylamine.

5. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 1 or 2, characterized in that: the solvent is one or more of dichloromethane, acetonitrile, N-dimethylformamide, N-dimethylacetamide, 1, 2-dichloroethane, tetrahydrofuran and dioxane.

6. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 5, characterized in that: the solvent is dichloromethane, acetonitrile, N-dimethylformamide or N, N-dimethylacetamide.

7. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 2, characterized in that: in the fourth step, the alcohol is one or more of ethanol, methanol and isopropanol.

8. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 2, characterized in that: and the temperature of reduced pressure distillation in the second step is 40-55 ℃.

9. The process for the preparation of N-phenylbis (trifluoromethanesulfonyl) imide according to claim 2, characterized in that: the mass ratio of the N-phenyl bis (trifluoromethanesulfonyl) imide crude product to the alcohols is 0.5: 1 to 5.

Technical Field

The invention relates to the field of fine chemical engineering, in particular to a preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide.

Background

N-phenyl bis (trifluoromethanesulfonyl) imide is a high-efficiency trifluoromethanesulfonylation reagent and is a reagent widely applied to pesticides, medical intermediates and organic materials. The method is mainly applied to the trifluoromethanesulfonyl chlorination of aliphatic aldehyde ketone (enol), phenols and amines. The method can also be applied to the synthesis of an abiraterone API serving as an active ingredient of the anti-prostate cancer medicine, and is shown as follows.

The synthetic route to N-phenylbis (trifluoromethanesulfonyl) imide has so far been the following three:

route 1:

route 2:

route 3:

for route 1, a number of patents and literature reports. For example, patent documents CN111269152A, CN103717214A, CN102250065A, CN105979779A, JP2003286244A, US20110230495A1, WO2015112441A1, WO2016027284A1, non-patent documents Tetrahedron Letters, 1973, #46, 4607-containing 4610 and Inorganic Chemistry, 49(3), 1252-containing 1265, 2010 report a process for preparing N-phenyl bis (trifluoromethanesulfonyl) imide in methylene chloride using aniline and trifluoromethanesulfonic anhydride as raw materials and triethylamine as an acid-binding agent. This method has the following key problems: 1) the price of the raw material trifluoromethanesulfonic anhydride is high, at least 2.0 equivalents of trifluoromethanesulfonic anhydride is consumed for 1.0 equivalent of aniline in the reaction, and a large amount of three-waste byproducts such as trifluoromethanesulfonate and the like are generated in the reaction, so that the process production cost is high; 2) because the early stage of the reaction system has violent heat release, the trifluoromethanesulfonic anhydride needs to be added dropwise under low-temperature stirring; 3) the reaction product has more impurities, and besides the trifluoromethanesulfonate, a lot of organic waste liquid also exist, so that the product purity is low; 4) the reaction conditions are severe, and the inert gas protection, low-temperature control and slow dropwise addition must be simultaneously satisfied to ensure the reaction yield (see JP 2003286244A).

For the route 2, patents CN111269152A and CN110627691A report that N-phenyl bis (trifluoromethanesulfonyl) imide is prepared by replacing polar solvent by a step method with trifluoromethanesulfonyl fluoride and aniline as raw materials, organic base as an acid-binding agent, and DMAP as a catalyst. There are also problems with this approach, the key of which is: 1) the trifluoromethanesulfonyl fluoride gas has low reaction activity, hydrogen fluoride gas is usually mixed in the electrolytic preparation process of trifluoromethanesulfonyl fluoride, aniline and organic alkali which are raw materials are consumed in the preparation process of N-phenyl bis (trifluoromethanesulfonyl) imide, and meanwhile, the trifluoromethanesulfonyl fluoride gas reacts with a catalyst DMAP to inactivate the catalyst, so that the reaction yield is influenced; in addition, the hydrogen fluoride has strong corrosivity, and a tight leakage-proof device needs to be designed in the using process to avoid burning of the hydrogen fluoride to the body; 2) the trifluoromethanesulfonyl fluoride is gas at normal temperature, the contact area between the trifluoromethanesulfonyl fluoride and aniline molecules is small in the reaction process, and only the trifluoromethanesulfonyl fluoride dissolved in a solvent can react with aniline, so that the contact area between the trifluoromethanesulfonyl fluoride and aniline which is liquid at normal temperature is not as large as that between the trifluoromethanesulfonyl chloride and aniline, and the reaction yield is influenced to a great extent; 3) the reaction rate is also influenced to a certain extent by too small trifluoromethanesulfonyl fluoride gas flow in the reaction, but the higher requirement on a reactor is met by too large gas flow pressure, and the process cost is indirectly increased.

For scheme 3, the Journal of Organic Chemistry, 72(18), 6758-6762, 2007 reports a process for preparing N-phenylbis (trifluoromethanesulfonyl) imide under nitrogen protection using an ionic liquid of diazobenzene tetrafluoroborate and 3- (1, 1-dimethylethyl) -1-methyl-1H-imidazolium bis (trifluoromethanesulfonyl) imide. The method has no market manufacturer because of the used raw material of the ionic liquid of the 3- (1, 1-dimethylethyl) -1-methyl-1H-imidazolium bis (trifluoromethanesulfonyl) imide salt, and the preparation process is relatively complex, not only has high cost, but also is difficult to industrially produce, so the process is generally rarely used.

Disclosure of Invention

In order to solve the technical problems, the invention provides a preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide, which adopts trifluoromethanesulfonyl chloride as a raw material, can avoid the problems of high cost and more three wastes caused by the fact that only one trifluoromethanesulfonyl group participates in the reaction when trifluoromethanesulfonic anhydride is adopted, and can also avoid the problem of low yield caused by low activity when trifluoromethanesulfonyl fluoride is adopted.

The technical scheme of the invention is as follows: a preparation method of N-phenyl bis (trifluoromethanesulfonyl) imide comprises the steps of preparing trifluoromethanesulfonic acid as a raw material to obtain trifluoromethanesulfonyl chloride; dissolving aniline in a solvent, and reacting the aniline with organic base serving as an acid-binding agent; then adding the obtained trifluoromethanesulfonyl chloride to react to obtain N-phenyl bis (trifluoromethanesulfonyl) imide.

Preferably, the specific steps are as follows: step one, slowly adding thionyl chloride into trifluoromethanesulfonic acid, adding a catalyst N, N-dimethylformamide, starting stirring, heating to 40-50 ℃ after 0.5 hour, and stirring for 4-12 hours to obtain a crude trifluoromethanesulfonyl chloride product;

step two, distilling the crude product of the trifluoromethanesulfonyl chloride under reduced pressure, and removing excessive thionyl chloride and N, N-dimethylformamide serving as a catalyst to obtain a pure product of the trifluoromethanesulfonyl chloride;

step three, dissolving aniline in a solvent, adding organic base as an acid-binding agent, and slowly dropwise adding trifluoromethanesulfonyl chloride obtained in the step two under ice bath to prepare a crude product of N-phenyl bis (trifluoromethanesulfonyl) imine;

distilling to remove the solvent, washing with water, and recrystallizing and washing with alcohol to obtain N-phenyl bis (trifluoromethanesulfonyl) imide;

preferably, the molar ratio of trifluoromethanesulfonic acid to thionyl chloride is 1: 4-10;

preferably, the molar ratio of triflic acid to catalyst is 1: 0.01 to 0.1

Preferably, the molar ratio of the trifluoromethanesulfonyl chloride to the aniline is 2.1-4: 1;

preferably, the molar ratio of the organic base to the aniline is 2-4: 1;

preferably, the organic base is one or more of triethylamine, N-diisopropylethylamine, triethylene diamine and hexamethylene tetramine.

Preferably, the solvent is one or more of dichloromethane, acetonitrile, N-dimethylformamide or N, N-dimethylacetamide.

Preferably, the alcohol used for recrystallizing the crude N-phenyl bis (trifluoromethanesulfonyl) imide is one or more of ethanol, methanol and isopropanol.

Preferably, the reduced pressure distillation temperature of the trifluoromethanesulfonyl chloride is 40-55 ℃.

Preferably, the mass ratio of the crude N-phenyl bis (trifluoromethanesulfonyl) imide to the alcohols is 0.5: 1 to 5.

According to the scheme, trifluoromethanesulfonic acid is used as a raw material, firstly trifluoromethanesulfonic acid is subjected to acylation reaction with thionyl chloride to obtain trifluoromethanesulfonyl chloride, and then the trifluoromethanesulfonyl chloride is reacted with aniline to obtain N-phenyl bis (trifluoromethanesulfonyl) imide.

Detailed Description

Example 1

150g (1mol) of trifluoromethanesulfonic acid is added into a reactor inserted with a thermometer, a distillation device and a mechanical stirrer, 290mL (4mol) of thionyl chloride is slowly added under ice bath, 0.74g (0.01mol) of N, N-dimethylformamide serving as a catalyst is added, the temperature is slowly raised to room temperature, the mixture is stirred for half an hour, the temperature is continuously raised to 40 ℃, the mixture is continuously stirred for 4 hours, the reaction is cooled to room temperature after the reaction is finished, reduced pressure distillation is carried out at 100 ℃ and-0.1 to-0.08 MPa, the temperature is slowly raised to 50 ℃ at the same time, 143g of trifluoromethanesulfonyl chloride is obtained, and the yield is 85.1%.

42g (0.42mol) aniline and 85.9g (0.85mol) triethylamine are dissolved in 2L dichloromethane, 143g (0.85mol) trifluoromethanesulfonyl chloride is slowly dropped in ice bath, the temperature is slowly raised to room temperature and stirred for 12 hours, after the reaction is finished, the temperature is kept at 40 ℃, the pressure is kept between-0.02 and-0.06 MPa, reduced pressure distillation is carried out to remove dichloromethane, 148g of light yellow solid is obtained, the solid is washed twice with water and recrystallized with 296g ethanol, 131g of N-phenyl bis (trifluoromethanesulfonyl) imine is obtained, and the yield is 80.1%.

Example 2

150g (1mol) of trifluoromethanesulfonic acid is added into a reactor inserted with a thermometer, a distillation device and a mechanical stirrer, 725mL (10mol) of thionyl chloride is slowly added under ice bath, 3.7g (0.05mol) of N, N-dimethylformamide serving as a catalyst is added, the temperature is slowly raised to room temperature, the mixture is stirred for half an hour, the temperature is continuously raised to 40 ℃, the mixture is continuously stirred for 8 hours, the reaction is cooled to room temperature after the reaction is finished, reduced pressure distillation is carried out at 120 ℃ and-0.1 to-0.08 MPa, the temperature is slowly raised to 50 ℃ at the same time, 139g of trifluoromethanesulfonyl chloride refined product is obtained, and the yield is 82.7%.

21g (0.21mol) aniline and 107.3g (0.83mol) N, N-diisopropylethylamine are dissolved in 2L acetonitrile, 139g (0.83mol) trifluoromethanesulfonyl chloride is slowly dropped in an ice bath, the temperature is slowly raised to room temperature and stirred for 12 hours, after the reaction is finished, the temperature is kept at 40 ℃ and the pressure is kept between-0.02 MPa and-0.06 MPa, reduced pressure distillation is carried out to remove acetonitrile, 154g pale yellow solid is obtained, the solid is washed twice by water and recrystallized by 1540g ethanol to obtain 122g N-phenyl bis (trifluoromethanesulfonyl) imide, and the yield is 74.6%.

Example 3

150g (1mol) of trifluoromethanesulfonic acid is added into a reactor inserted with a thermometer, a distillation device and a mechanical stirrer, 435mL (6mol) of thionyl chloride is slowly added under ice bath, 7.36(0.1mol) of N, N-dimethylformamide serving as a catalyst is added, the temperature is slowly raised to room temperature, the mixture is stirred for half an hour, the temperature is continuously raised to 40 ℃, the mixture is continuously stirred for 12 hours, the reaction temperature is lowered to room temperature after the reaction is finished, reduced pressure distillation is carried out at 110 ℃ and-0.1 to-0.08 MPa, the temperature is slowly raised to 50 ℃ at the same time, 147g of trifluoromethanesulfonyl chloride refined product is obtained, and the yield is 87.5%.

Dissolving 21g (0.21mol) of aniline and 83.8g (0.83mol) of triethylamine in 2.5L of N, N-dimethylformamide, slowly dropwise adding 139g (0.83mol) of trifluoromethanesulfonyl chloride in ice bath, slowly raising the temperature to room temperature, stirring for 12 hours, after the reaction is finished, keeping the temperature at 40 ℃, and carrying out reduced pressure distillation under the pressure of-0.02 to-0.06 MPa to remove acetonitrile to obtain 154g of light yellow solid, washing the solid twice with water, and recrystallizing with 770g of ethanol to obtain 126g of N-phenyl bis (trifluoromethanesulfonyl) imide, wherein the yield is 77.1%.

The method has the advantages of full reaction of reactants, easy pollution discharge after the reaction, mild reaction conditions, no high temperature and high pressure, less three wastes, simple post-treatment, recyclable solvent and reduced pollution in the synthesis process, and belongs to a green synthesis process. In summary, the above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.