阅读说明：本技术 季铵盐-73的合成方法 (Synthesis method of quaternary ammonium salt-73 ) 是由 付杰 王一霖 于 2021-09-09 设计创作，主要内容包括：本申请涉及化学合成技术领域,提供了一种季铵盐-73的合成方法,包括步骤：(1)丙二酰胺发生硫代反应,得到式(Ⅰ)化合物；(2)式(Ⅰ)化合物和氯丙酮发生反应,得到式(Ⅱ)化合物；(3)将式(Ⅱ)化合物脱盐,在有机溶剂存在的条件下脱氢后和碘庚烷发生反应,得到式(Ⅲ)化合物；(4)式(Ⅲ)化合物和碘庚烷发生反应,得到式(Ⅳ)化合物,即季铵盐-73。该制备方法采用的原料廉价易得,操作简单,反应过程可控,产物易于分离纯化,总收率高,纯度高,适合工业化规模生产。(The application relates to the technical field of chemical synthesis, and provides a synthesis method of quaternary ammonium salt-73, which comprises the following steps: (1) carrying out a thionation reaction on malonamide to obtain a compound shown in a formula (I); (2) reacting the compound shown in the formula (I) with chloropropanone to obtain a compound shown in a formula (II); (3) desalting a compound shown in a formula (II), dehydrogenating the compound in the presence of an organic solvent, and reacting the compound with iodoheptane to obtain a compound shown in a formula (III); (4) and (3) reacting the compound shown in the formula (III) with iodoheptane to obtain the compound shown in the formula (IV), namely quaternary ammonium salt-73. The preparation method has the advantages of cheap and easily-obtained raw materials, simple operation, controllable reaction process, easy separation and purification of products, high total yield and high purity, and is suitable for industrial mass production.)

1. A method for synthesizing quaternary ammonium salt-73 is characterized by comprising the following steps:

(1) carrying out a thionation reaction on malonamide to obtain a compound shown in a formula (I);

(2) reacting the compound shown in the formula (I) with chloropropanone to obtain a compound shown in a formula (II);

(3) desalting the compound of the formula (II), dehydrogenating the compound of the formula (II) in the presence of an organic solvent, and reacting the compound of the formula (II) with iodoheptane to obtain a compound of a formula (III);

(4) reacting the compound shown in the formula (III) with iodoheptane to obtain a compound shown in the formula (IV), namely quaternary ammonium salt-73;

2. the method of synthesis according to claim 1, characterized in that: in the step (1), the thioreagent used in the thioreaction comprises at least one of Lawesson reagent and phosphorus pentasulfide, and the molar ratio of the thioreagent to the malonamide is 2.0-2.4: 2.

3. the method of synthesis according to claim 1, characterized in that: in the step (1), the temperature of the thionation reaction is 75-90 ℃.

4. The method of synthesis according to claim 1, characterized in that: in the step (1), the thionation reaction is carried out in an aprotic solvent, and the aprotic solvent includes at least one of tetrahydrofuran, dioxane, toluene, ethyl acetate, and acetonitrile.

5. The method of synthesis according to claim 1, characterized in that: in the step (2), the molar ratio of the compound shown in the formula (I) to the chloroacetone is 1: 2.1-2.5.

6. The method of synthesis according to claim 1, characterized in that: in the step (2), the reaction temperature is 60-70 ℃.

7. The method of synthesis according to claim 1, characterized in that: in the step (2), the reaction is carried out in an organic solvent including at least one of N, N-dimethylformamide, N-dimethylacetamide, methanol and ethanol.

8. The method of synthesis according to claim 1, characterized in that: in the step (3), the desalting is performed by using an alkaline substance.

9. The method of synthesis according to claim 8, characterized in that: in the step (3), the alkaline substance includes at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.

10. The method of synthesis according to claim 1, characterized in that: in the step (3), the organic solvent includes at least one of tetrahydrofuran, tert-butanol, dioxane and ethanol.

11. The method of synthesis according to claim 1, characterized in that: in the step (3), the dehydrogenation is carried out by using strong alkali.

12. The method of synthesis according to claim 11, characterized in that: in the step (3), the strong base includes at least one of potassium tert-butoxide, sodium methoxide and sodium ethoxide.

13. The method of synthesis according to claim 11, characterized in that: in the step (3), the molar ratio of the compound shown in the formula (II) to the strong base is 1: 1.1-1.2.

14. The method of synthesis according to claim 1, characterized in that: in the step (3), the molar ratio of the compound shown in the formula (II) to the iodoheptane is 1: 1.1-1.2.

15. The method of synthesis according to claim 1, characterized in that: in the step (3), the reaction temperature is 25-35 ℃.

16. The method of synthesis according to claim 1, characterized in that: in step (4), the molar ratio of the compound of formula (III) to the iodoheptane is 1: 1.2-1.5.

17. The method of synthesis according to claim 1, characterized in that: in the step (4), the reaction temperature is 130-150 ℃, and the reaction time is 16-20 h.

18. The method of synthesis according to claim 1, characterized in that: in the step (4), the reaction is carried out in an organic solvent, and the organic solvent is xylene.

19. Quaternary ammonium salt-73 made according to the synthetic method of any one of claims 1-18.

Technical Field

The application relates to the technical field of chemical synthesis, in particular to a synthesis method of quaternary ammonium salt-73.

Background

The quaternary ammonium salt-73 has strong antibacterial activity, has strong killing capability on staphylococcus, escherichia coli and the like, and can be used as a preservative; in addition, it has effect in inhibiting melanogenesis. The quaternary ammonium salt-73 has good effects of sterilization, whitening and the like and high use safety, is widely applied to acne removal, whitening and freckle removal products, and is highly favored by consumers.

In the synthesis process of the quaternary ammonium salt-73, 4-methylthiazole-2-thiol and 2-aminopropanethiol are mostly adopted as raw materials, but the price of the raw material 4-methylthiazole-2-thiol is high, and the 2-aminopropanethiol is not supplied in large quantities in the market, so that the synthesis cost is extremely high, and the industrial production is difficult to realize.

Disclosure of Invention

The application aims to provide a novel synthesis method of quaternary ammonium salt-73 so as to reduce the synthesis cost.

The application provides a synthesis method of quaternary ammonium salt-73, which comprises the following steps:

(1) carrying out a thionation reaction on malonamide to obtain a compound shown in a formula (I);

(2) reacting the compound shown in the formula (I) with chloropropanone to obtain a compound shown in a formula (II);

(3) desalting a compound shown in a formula (II), dehydrogenating the compound in the presence of an organic solvent, and reacting the compound with iodoheptane to obtain a compound shown in a formula (III);

(4) reacting the compound shown in the formula (III) with iodoheptane to obtain a compound shown in the formula (IV), namely quaternary ammonium salt-73;

in some embodiments, in step (1), the thionating agent used in the thionation reaction comprises at least one of Lawesson's reagent and phosphorus pentasulfide, and the molar ratio of the thionating agent to malonamide is 2.0-2.4: 2.

in some embodiments, the temperature of the thionation reaction in step (1) is from 75 ℃ to 90 ℃.

In some embodiments, in step (1), the thionation reaction is carried out in an aprotic solvent comprising at least one of tetrahydrofuran, dioxane, toluene, ethyl acetate, and acetonitrile.

In some embodiments, in step (2), the compound of formula (i) and chloroacetone are present in a molar ratio of 1: 2.1-2.5.

In some embodiments, the temperature of the reaction in step (2) is from 60 ℃ to 70 ℃.

In some embodiments, in step (2), the reaction is carried out in an organic solvent comprising at least one of N, N-dimethylformamide, N-dimethylacetamide, methanol, and ethanol.

In some embodiments, in step (3), desalting is performed with an alkaline substance.

In some embodiments, in step (3), the organic solvent comprises at least one of tetrahydrofuran, tert-butanol, dioxane, and ethanol.

In some embodiments, step (3), the dehydrogenation is performed with a strong base.

In some embodiments, in step (3), the strong base comprises at least one of potassium tert-butoxide, sodium methoxide and sodium ethoxide.

In some embodiments, in step (3), the molar ratio of the compound of formula (ii) to the strong base is 1: 1.1-1.2.

In some embodiments, in step (3), the compound of formula (ii) and iodoheptane are present in a 1: 1.1-1.2.

In some embodiments, the temperature of the reaction in step (3) is from 25 ℃ to 35 ℃.

In some embodiments, in step (4), the compound of formula (iii) and iodoheptane are present in a 1: 1.2-1.5.

In some embodiments, in step (4), the temperature of the reaction is 130 ℃ to 150 ℃ and the reaction time is 16h to 20 h.

In some embodiments, in step (4), the reaction is carried out in an organic solvent, which is xylene.

The present application also provides a quaternary ammonium salt-73 prepared according to any of the above-described synthetic methods.

According to the synthesis method of the quaternary ammonium salt-73, cheap and easily-obtained malonamide is used as a raw material, so that the synthesis cost is greatly reduced; the operation is simple, the reaction process is controllable, and the product is easy to separate and purify; the total yield of the quaternary ammonium salt-73 is not less than 50 percent, the purity is not less than 99 percent, and the method is suitable for industrial mass production.

Of course, not all advantages described above need to be achieved at the same time in the practice of any one product or method of the present application.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present application, and it is also obvious for a person skilled in the art to obtain other embodiments according to the drawings.

FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula (IV) in example 7.

Detailed Description

The technical solutions in the present application will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present application, and it is obvious that the described embodiments are only some embodiments of the present application, not all embodiments. All other embodiments that can be derived by one of ordinary skill in the art from the description herein are intended to be within the scope of the present disclosure.

The application provides a synthetic method of quaternary ammonium salt-73, and the synthetic route is as follows:

wherein, the step (1): carrying out a thionation reaction on malonamide to obtain a compound shown in a formula (I);

step (2): reacting the compound shown in the formula (I) with chloropropanone to obtain a compound shown in a formula (II);

and (3): desalting a compound shown in a formula (II), dehydrogenating the compound in the presence of an organic solvent, and reacting the compound with iodoheptane to obtain a compound shown in a formula (III);

and (4): and (3) reacting the compound shown in the formula (III) with iodoheptane to obtain the compound shown in the formula (IV), namely quaternary ammonium salt-73.

In the step (1), malonamide is subjected to a thio reaction, and the obtained product is separated to obtain the compound shown in the formula (I). The reaction process can be monitored by High Performance Liquid Chromatography (HPLC), and the reaction can be terminated after the reaction of the raw materials is detected. The method for separating the product is not particularly limited as long as the object of the present invention can be achieved, and for example, the product obtained by the reaction may be adjusted to room temperature and the solvent may be concentrated; adding dichloromethane, stirring and completely crystallizing; filtering, washing the filter cake with dichloromethane to obtain light yellow crystals, namely the compound of the formula (I).

In some embodiments of the present application, the thionating agent used in the thionation reaction includes at least one of Lawesson's reagent and phosphorus pentasulfide, and the molar ratio of the thionating agent to malonamide is 2.0 to 2.4: 2.

in some embodiments herein, the temperature of the thionation reaction is from 75 ℃ to 90 ℃.

The manner of temperature control during the thionation reaction is not limited in the present application as long as the object of the present application can be achieved, and for example, heating in an oil bath may be carried out while maintaining a desired temperature.

In some embodiments herein, the thionation reaction is carried out in an aprotic solvent comprising at least one of tetrahydrofuran, dioxane, toluene, ethyl acetate, and acetonitrile.

The amount of the aprotic solvent used herein is not particularly limited as long as the object of the present application can be achieved, and for example, the ratio of the volume of the aprotic solvent to the molar amount of the malonamide is 2L to 2.4L: 2 mol.

In the step (2), the compound of the formula (I) and chloropropanone are subjected to Hantzsch thiazole synthesis reaction, and the obtained product is separated to obtain the compound of the formula (II). HPLC can be used for monitoring in the reaction process, and the reaction can be terminated after the reaction of the raw materials is detected. The method for separating the product is not particularly limited as long as the object of the present invention can be achieved, and for example, ethyl acetate may be added to the product obtained by the reaction to precipitate crystals; filtering, and washing a filter cake by using ethyl acetate; recrystallizing the filter cake with ethanol to obtain a mauve crystal, namely the compound shown in the formula (II).

In some embodiments of the present application, the molar ratio of the compound of formula (i) to chloroacetone is 1: 2.1-2.5.

In some embodiments of the present application, the temperature of the reaction is from 60 ℃ to 70 ℃.

The manner of temperature control in the reaction process is not limited in the present application as long as the object of the present application can be achieved, and for example, heating may be performed in an oil bath to maintain a desired temperature.

In some embodiments herein, the reaction is carried out in an organic solvent comprising at least one of N, N-dimethylformamide, N-dimethylacetamide, methanol, and ethanol.

The amount of the organic solvent used herein is not particularly limited as long as the object of the present invention can be achieved, and for example, the ratio of the volume of the organic solvent to the mole of the compound of formula (i) is 0.8L to 0.9L: 1 mol.

In the step (3), the compound shown in the formula (II) is desalted, dehydrogenated in the presence of an organic solvent, and subjected to Hofmann alkylation reaction with iodoheptane, and a product obtained by the reaction is separated to obtain the compound shown in the formula (III). HPLC can be used for monitoring in the reaction process, and the reaction can be terminated after the reaction of the raw materials is detected. The method for separating the product is not particularly limited as long as the object of the present invention can be achieved, and for example, the product obtained by the reaction may be added to water, followed by extraction with ethyl acetate for a plurality of times, for example, twice, washing the extract with brine, drying with anhydrous sodium sulfate, and filtering; dripping the collected filtrate into a hydrochloric acid ethanol solution for acidification, and separating out crystals; filtering, and washing a filter cake by using ethyl acetate; adding the collected filter cake into water, and adjusting the pH value to be alkaline; extracting with ethyl acetate, washing the extract with saturated saline solution, drying with anhydrous sodium sulfate, and concentrating to obtain light purple liquid, i.e. the compound of formula (III).

In some embodiments of the present application, desalting is performed with a basic substance; in a further embodiment of the present application, the alkaline substance comprises at least one of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.

The specific method of desalting is not limited as long as the object of the present invention can be achieved, and for example, the compound of formula (II) is added to water, and then the pH is adjusted to be alkaline with an alkaline solution; extraction was performed with ethyl acetate, and the extract was washed with water and saturated brine in this order, dried over anhydrous sodium sulfate, and then concentrated to remove ethyl acetate.

In some embodiments herein, the organic solvent comprises at least one of tetrahydrofuran, tert-butanol, dioxane, and ethanol.

The amount of the organic solvent used herein is not particularly limited as long as the object of the present invention can be achieved, and for example, the ratio of the volume of the organic solvent to the mole of the compound of formula (ii) is 0.7L to 1L: 0.5 mol.

In some embodiments of the present application, the dehydrogenation is carried out using a strong base; in further embodiments herein, the strong base comprises at least one of potassium tert-butoxide, sodium methoxide and sodium ethoxide; in a further embodiment of the present application, the molar ratio of the compound of formula (ii) to the strong base is 1: 1.1-1.2.

In some embodiments of the present application, the molar ratio of the compound of formula (ii) to iodoheptane is 1: 1.1-1.2.

In some embodiments of the present application, the temperature of the reaction is from 25 ℃ to 35 ℃.

The method for controlling the temperature in the reaction process is not limited, so long as the purpose of the method can be achieved.

In the step (4), the compound of the formula (III) and iodoheptane react under the solvent-free condition, and the product obtained by the reaction is separated to obtain the compound of the formula (IV), namely the quaternary ammonium salt-73. HPLC can be used for monitoring in the reaction process, and the reaction can be terminated after the reaction of the raw materials is detected. The method for separating the product is not particularly limited as long as the object of the present invention can be achieved, and for example, the product obtained by the reaction may be adjusted to room temperature, filtered, and the filter cake may be washed with ethyl acetate to obtain a crude orange red product; then ethanol is adopted for recrystallization to obtain golden yellow crystal, namely the compound quaternary ammonium salt-73 of the formula (IV).

In some embodiments of the present application, the compound of formula (iii) and iodoheptane are present in a molar ratio of 1: 1.2-1.5.

In some embodiments herein, the temperature of the reaction is from 130 ℃ to 150 ℃ and the time of the reaction is from 16h to 20 h.

In some embodiments of the present application, the compound of formula (iii) and iodoheptane are reacted in the organic solvent xylene.

The amount of the organic solvent used herein is not particularly limited as long as the object of the present application can be achieved, and for example, the ratio of the volume of the organic solvent to the mole of the compound of formula (iii) is 1L: 1 mol.

The present application also provides a quaternary ammonium salt-73 prepared according to any of the above-described synthetic methods.

The present application will be described in detail with reference to specific examples.

And (3) calculating yield:

the yield is the mass of the actual synthesis product/the mass of the theoretical synthesis product x 100%.

And (3) purity testing: the purity of the product was checked by High Performance Liquid Chromatography (HPLC).

Example 1

A5L reaction flask was charged with 204g (2mol) of malonamide, 968g (2.4mol) of Lawesson's reagent and 2L of tetrahydrofuran, and placed in an oil bath and heated to 75 ℃ with stirring. The reaction progress was monitored by HPLC and by 8h, the reaction was stopped when complete reaction of the starting material was detected.

Cooling the reaction mixture to room temperature, and concentrating to remove about 1.2L of tetrahydrofuran; adding 2L of dichloromethane, stirring and completely crystallizing; filtration and washing of the filter cake with dichloromethane gave 241g of pale yellow crystals of the compound of formula (I) (yield 89.6%, purity 99%).

Example 2

A3L reaction flask was charged with 102g (1mol) of malonamide, 191.3g (1mol) of phosphorus pentasulfide and 1.2L of dioxane, and placed in an oil bath to be heated to 90 ℃ with stirring. The reaction progress was monitored by HPLC and by 9h, the reaction was stopped when complete reaction of the starting material was detected.

Cooling the reaction mixture to room temperature, filtering, and concentrating the filtrate to remove about 0.5L of dioxane; adding 2L of dichloromethane, stirring and completely crystallizing; filtration and washing of the filter cake with dichloromethane gave 109.9g of pale yellow crystals of the compound of formula (I) (yield 82.0%, purity 99%).

Example 3

A4L reaction flask was charged with 134g (1mol) of the compound of formula (I) and 0.9L N, N-dimethylformamide; stirring, and pumping nitrogen for three times; 204g (2.2mol) of chloroacetone are added and the mixture is heated in an oil bath to 60 ℃. The reaction progress was monitored by HPLC and by 16h, the reaction was stopped when complete reaction of the starting material was detected.

2.7L of ethyl acetate was poured into the mixture obtained after the reaction, and a large amount of purplish red crystals were precipitated; filtering, and washing a filter cake with a little ethyl acetate; the filter cake was recrystallized from ethanol to give 272g of a purple-red crystal of the compound of formula (II) (yield 96.2%, purity 98%).

Example 4

A1L reaction flask was charged with 26.8g (0.2mol) of the compound of formula (I) and 0.16L N, N-dimethylacetamide; stirring, and pumping nitrogen for three times; 42.6g (0.46mol) of chloroacetone are added and the mixture is heated in an oil bath to 60 ℃. The reaction progress was monitored by HPLC and by 18h, the reaction was stopped when complete reaction of the starting material was detected.

0.7L of ethyl acetate was poured into the mixture obtained after the reaction, and a large amount of purplish red crystals were precipitated; filtering, and washing a filter cake with a little ethyl acetate; the filter cake was recrystallized from ethanol to give 51.5g of a magenta crystal of the compound of the formula (II) (yield 91.0%, purity 97.5%).

Example 5

142g (0.5mol) of the compound of formula (II) are added to 0.5L of water, and the pH is adjusted to 10 by 10% by weight sodium hydroxide solution; then, the mixture is extracted by ethyl acetate, and the extract liquid is washed by water and saturated saline water in turn, dried by anhydrous sodium sulfate and concentrated to remove ethyl acetate, so that light purple transparent liquid is obtained.

The above pale purple transparent liquid was charged into a 2L reaction flask, and 0.7L of t-butanol and 61.6g (0.55mol) of potassium t-butoxide were added and stirred at room temperature for 1 hour. 124.3g (0.55mol) of iodoheptane were added, and the reaction was stirred at 30 ℃. The reaction progress was monitored by HPLC and by 8h, the reaction was stopped when complete reaction of the starting material was detected.

Adding 0.7L of water into the mixture obtained after the reaction, extracting twice by adopting ethyl acetate, washing the extract by using water and saturated saline solution in sequence, drying the extract by using anhydrous sodium sulfate, and filtering; dripping the collected filtrate into a hydrochloric acid ethanol solution for acidification, separating out crystals, filtering, and washing a filter cake with ethyl acetate; adding the collected filter cake into water, and adjusting the pH value to 10 by using a sodium hydroxide solution with the mass fraction of 10%; extraction was performed with ethyl acetate, and the extract was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated to obtain 141.8g of a pale purple liquid, i.e., the compound of formula (III) (yield 91.9%, purity 98%).

Example 6

28.3g (0.1mol) of the compound of formula (ii) are added to 0.1L of water and the pH is adjusted to 10 with 10% by weight sodium hydroxide solution; extracting with ethyl acetate, washing the extractive solution with water and saturated saline solution, drying with anhydrous sodium sulfate, and concentrating to remove ethyl acetate to obtain light purple transparent liquid.

The above pale purple transparent liquid was charged into a 0.5L reaction flask, and 0.2L of tetrahydrofuran and 12.3g (0.11mol) of potassium tert-butoxide were added and stirred at room temperature for 1 hour. 24.9g (0.11mol) of iodoheptane were added, and the reaction was stirred at 30 ℃. The reaction progress was monitored by HPLC and by 10h, the reaction was stopped when complete reaction of the starting material was detected.

Adding 0.14L of water into the mixture obtained after the reaction, extracting twice by adopting ethyl acetate, washing the extract by using water and saturated saline solution in sequence, drying the extract by using anhydrous sodium sulfate, and filtering; dripping the collected filtrate into a hydrochloric acid ethanol solution for acidification, separating out crystals, filtering, and washing a filter cake with ethyl acetate; adding the collected filter cake into water, and adjusting the pH value to 10 by using a sodium hydroxide solution with the mass fraction of 10%; extraction was performed with ethyl acetate, and the extract was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated to obtain 27.5g of a pale purple liquid, i.e., the compound of formula (III) (yield 89.2%, purity 98%).

Example 7

141.8g (0.46mol) of the compound of the formula (III) are introduced into a 1L reaction vessel, purged with nitrogen three times and 188g (0.83mol) of iodoheptane are added; the oil bath was heated to 150 ℃. The reaction progress was monitored by HPLC and by 16h, the reaction was stopped when complete reaction of the starting material was detected.

Cooling the mixture obtained after the reaction to room temperature, filtering, and washing a filter cake with ethyl acetate to obtain 213.9g of orange-red crude product; after this time, recrystallization from ethanol gave 188.2g of a yellow crystal of the compound of the formula (IV) (yield 88%, purity 99%).

The nuclear magnetic resonance hydrogen spectrum of the compound shown in the formula (IV) is shown in figure 1, and the compound shown in the formula (IV) is identified and confirmed to be quaternary ammonium salt-73.

Example 8

15.4g (50mmol) of the compound of formula (III), 50mL of xylene, three times with nitrogen purge, and 20.4g (90mmol) of iodoheptane were placed in a 100mL reaction flask; the oil bath was heated to 130 ℃. The reaction progress was monitored by HPLC and by 20h, the reaction was stopped when complete reaction of the starting material was detected.

Cooling the mixture obtained after the reaction to room temperature, filtering, and washing a filter cake with ethyl acetate to obtain 17.6g of orange-red crude product; then, recrystallization from ethanol gave 14.2g of a yellow crystal of the compound of the formula (IV) (yield 80.7%, purity 99%).

The compound shown in the formula (IV) is identified and confirmed to be quaternary ammonium salt-73 by nuclear magnetic resonance hydrogen spectrogram.

The embodiment shows that the synthesis method of the quaternary ammonium salt-73 provided by the application has the advantages that in the preparation process, the adopted raw material malonamide is cheap and easy to obtain, and the synthesis cost is greatly reduced; the operation is simple, the reaction process is controllable, and the potential safety hazard in the production process can be effectively avoided; the total reaction yield is not lower than 50 percent, and the purity is not lower than 99 percent; can be widely applied to industrial production.

All the embodiments in the present specification are described in a related manner, and the same and similar parts among the embodiments may be referred to each other, and each embodiment focuses on the differences from the other embodiments.

The above description is only for the preferred embodiment of the present application and is not intended to limit the scope of the present application. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application are included in the protection scope of the present application.