Process for the preparation of an apogossypol intermediate

Abstract

The application discloses a preparation method of an apophenine intermediate. Vitamin A key intermediate raw material pentavalent aldehyde is used to synthesize C10 dialdehyde, the key intermediate of apophenine, through four steps of salification, addition, coupling and hydrolysis. The process has the advantages of mild reaction condition, short reaction steps, raw material relying on an industrial chain, high single-pass yield and the like. The tandem yield of C10 dialdehyde synthesized by using the process is high.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for preparing an apoester intermediate. Background Technology

[0002] Apocarboxylate, also known as β-apo-8'-carotene ethyl ester, apocarotene ethyl ester, natural orange No. 7, etc., has the chemical formula C. 32 H 44 O2, molecular weight 460.70, CAS number 1109-11-1, melting point 134-136℃, density 1.0±0.1g / cm³ 3 It appears as a dark purple crystalline solid. The recommended storage temperature is -20℃. It is sensitive to light and air, and it is recommended to store it in an inert gas container. Apoester is a chemically synthesized carotenoid compound with oxygen-containing functional groups. It is one of the apocarotenoids, containing 30 unsaturated conjugated carbon chains, and is a fat-soluble yellow pigment.

[0003] There are three main routes for the synthesis of aporyl ester: 1) the C25+C2+C3 route; 2) the C10+C20 route; and 3) the C15+C10+C5 route. For route 1, vinyl ethyl ether is used as the raw material for the C2 synthesis. However, vinyl ethyl ether is difficult to store and poses a significant risk in large-scale production. For route 2, although the C20 phosphine salt can be isolated from the vitamin A synthesis system, the C10 synthesis process is lengthy, involves numerous raw materials and auxiliary materials, generates substantial waste, and is costly. Therefore, the C15+C10+C5 route is primarily used in industrial production. Among these, the C10 dialdehyde, as a key intermediate in the synthesis of aporyl ester, is crucial.

[0004] Deca-dialdehyde, chemically named 2,7-dimethyl-2,4,6-octtrien-1,8-dialdehyde, or C10 dialdehyde for short, is a crucial intermediate in the synthesis of carotenoids. Chinese patent CN1918099A uses an aqueous sodium bicarbonate solution in the elimination reaction for the synthesis of C10 dialdehyde, with the reaction temperature set at 70-90℃. As is well known, sodium bicarbonate decomposes easily upon heating, leading to a continuous decrease in the catalytic efficiency of the catalyst in the system. Furthermore, the organic phase requires additional water washing to remove water-soluble impurities, increasing wastewater generation and production costs. In the method for preparing C10 dialdehyde via enol ether condensation, the elimination reaction is a critical step. However, the use of strong bases in known routes places high demands on equipment and reduces the product quality of C10 dialdehyde, while the use of weak bases leads to increased waste. Therefore, developing a green, environmentally friendly, high-quality, and low-cost production process is essential for the synthesis of deca-C10 dialdehyde. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a method for preparing apoester intermediates. This process synthesizes the key vitamin A intermediate C10 dialdehyde from pentacarbon aldehyde through four steps: salt formation, addition, coupling, and hydrolysis. The process offers advantages such as mild reaction conditions, short reaction steps, reliance on the raw material supply chain, and high single-pass yield. The tandem yield of C10 dialdehyde synthesized using this process is also high.

[0006] To achieve the purpose of the invention, the present invention adopts the following technical solution:

[0007] A method for preparing an apoester intermediate includes the following steps:

[0008] (1) Pentaldehyde reacts with organophosphine in the presence of acid to form compound 1;

[0009] (2) Compound 1 undergoes an addition reaction under the action of a catalyst to generate compound 2;

[0010] (3) Compound 2 undergoes a coupling reaction with peroxide to generate compound 3;

[0011] (4) Compound 3 undergoes hydrolysis under acidic conditions to produce C10 dialdehyde.

[0012] Preferably, the structural formula of the pentacarbonaldehyde is:

[0013] Preferably, the structural formula of the C10 dialdehyde is:

[0014]

[0015] Preferably, in step (1), the acid is an inorganic acid, such as one or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrogen fluoride, and hydrogen bromide, with hydrogen bromide being preferred.

[0016] Preferably, the organophosphorus is an aryl organophosphorus compound, such as triphenylphosphine, trioctylphosphine, triphenylphosphine chloride, triphenylphosphine hydrochloride, and benzyldiadamantylphosphine, with triphenylphosphine being the most preferred.

[0017] The molar ratio of the pentaldehyde to the organophosphorus acid is 1:(0.5-5.0):(0.5-5.0), preferably 1:(1-3.0):(1-3.0).

[0018] Preferably, step (1) is carried out in a solvent, which is one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol, tert-butanol, etc., with methanol being preferred.

[0019] Preferably, the mass of solvent added to each gram of pentacarbonaldehyde is 0.5-10g, more preferably 1-5g.

[0020] In step (1), the reaction temperature is -20 to 70°C, preferably 10 to 50°C;

[0021] In step (1), the reaction pressure is 0.01 to 10.0 MPa, preferably 0.1 to 5.0 MPa;

[0022] In step (1), the reaction time is 1-20 hours, preferably 5-10 hours;

[0023] In step (1), the reaction is carried out under stirring conditions, with a stirring speed of 100-1000 rpm, preferably 200-500 rpm.

[0024] In this invention, the catalyst in step (2) is an inorganic salt containing hydrogen in the anion, such as one or more of sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium bisulfate, potassium bisulfate, sodium bisulfite, and potassium bisulfite, with sodium bisulfite being preferred.

[0025] Preferably, the reaction in step (2) is carried out in a solvent, which is one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol, tert-butanol, and water, with water being preferred. Preferably, the mass of solvent added to each gram of compound 1 is 0.2-10g, more preferably 1-5g.

[0026] Preferably, in step (2), the molar ratio of compound 1 to catalyst is 1:(1-10), more preferably 1:(1-5).

[0027] The reaction temperature in step (2) is 80-150℃, preferably 100-125℃;

[0028] The reaction pressure in step (2) is 0.1–10.0 MPa, preferably 1–2.0 MPa;

[0029] The reaction time in step (2) is 0.5-10 h, preferably 1-5 h;

[0030] The reaction in step (2) is carried out under stirring conditions, with a stirring speed of 50-800 rpm, preferably 100-500 rpm.

[0031] In this invention, the coupling reaction in step (3) occurs under the catalysis of a peroxide, wherein the peroxide is one or more of hydrogen peroxide, sodium peroxide, potassium peroxide, calcium peroxide, and benzamide peroxide, preferably hydrogen peroxide; the molar ratio of compound 2 to the peroxide is 1:(0.1-10), preferably 1:(1-5). The mass concentration of the peroxide is 1-80 wt%, preferably 5-50 wt%.

[0032] The reaction temperature in step (3) is -10 to 50°C, preferably 0 to 30°C;

[0033] The reaction pressure in step (3) is 0.1 to 10.0 MPa, preferably 1.5 to 4.0 MPa;

[0034] The reaction time in step (3) is 0.5-12 h, preferably 5-9 h;

[0035] The reaction in step (3) is carried out under stirring conditions, with a stirring speed of 50-800 rpm, preferably 200-500 rpm.

[0036] In this invention, the acidic environment in step (4) is formed by adding an acid compound, which is one or more of sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, and hydrobromic acid, with sulfuric acid being preferred. The pH value of the acidic environment is 1-7 (not equal to 7), preferably 3-5.

[0037] The reaction temperature in step (4) is 50-100℃, preferably 60-90℃;

[0038] The reaction pressure in step (4) is 0.1 to 10.0 MPa, preferably 1.0 to 5.0 MPa;

[0039] The reaction time in step (4) is 1-10 hours, preferably 3-7 hours;

[0040] The reaction in step (4) is carried out under stirring conditions, with a stirring speed of 20-800 rpm, preferably 100-500 rpm.

[0041] The specific synthesis route is shown below:

[0042]

[0043] The beneficial effects of this invention are as follows:

[0044] This invention discloses a method for preparing C10 dialdehyde, an intermediate of apoester. The process has advantages such as mild reaction conditions, short reaction steps, reliance on the raw material industrial chain, and single-pass operation. The tandem yield of C10 dialdehyde synthesized using this process is high. Attached Figure Description

[0045] Figure 1 The 1H NMR spectrum of compound 1 prepared in Example 1;

[0046] Figure 2 The 1H NMR spectrum of compound 2 obtained in Example 1;

[0047] Figure 3 The image shows the 1H NMR spectrum of the C5 phosphine salt obtained in Example 1.

[0048] Figure 4 The NMR spectrum of the C10 dialdehyde prepared in Example 1 is shown. Detailed Implementation

[0049] The solvents methanol, ethanol, and dichloromethane used in this invention were purchased from Shanghai Titan Technology Co., Ltd., sodium sulfite, sodium hydrogen sulfite, triphenylphosphine, hydrogen peroxide, sulfuric acid, and hydrochloric acid were purchased from Aladdin Reagent Co., Ltd., and pentaldehyde was purchased from BASF Chemical Co., Ltd., with a purity of 99%.

[0050] The structural formula of the pentacarbon aldehyde is shown below, with a molecular weight of 142 g / mol.

[0051]

[0052] In the following embodiments of the present invention, the content and purity of each component were obtained by testing and calculation using the external standard method of high performance liquid chromatography (HPLC), and the conversion rate was calculated based on the content of the product. The HPLC conditions were as follows: column: Waters XSelect HSS T3, 4.6 μm × 250 mm; injection volume: 2–10 μL, fine-tuned according to sample conditions; column temperature: 40 °C; flow rate: 1 mL / min; detector: ultraviolet detector (UV), detection wavelength 254–400 nm; mobile phase: acetonitrile / 0.1% phosphoric acid aqueous solution. During sample analysis, an external standard curve was first established using the pure product, and the mass fraction (content) of each detected substance was calculated based on the linear relationship between concentration and peak area. The analysis of each component in the oxidant was performed using ion chromatography, and the conditions for ion chromatography were the same as those for HPLC.

[0053] Example 1:

[0054] Preparation of compound 1: 1 mol of 142 g of pentanealdehyde was placed in a 1 L three-necked flask. The stirring speed was set to 200 rpm. 142 g of methanol and 1 mol of 262.3 g of triphenylphosphine were added, and 1 mol of hydrogen bromide was introduced. The system temperature was adjusted to 10 °C and the pressure was adjusted to 0.1 MPa. The reaction was continued for 5 h. After solvent removal, crystals of compound 1 were obtained. The purity of the liquid chromatography was about 99%, and the product yield was 96.3%.

[0055] Preparation of compound 2: Compound 1 prepared in the above steps was dissolved in 425.3 g of deionized water. The stirring speed was set to 100 rpm, and 1 mol of solid sodium bisulfite was added. The system temperature was adjusted to 100 °C and the pressure was adjusted to 1.0 MPa. After reacting for 1 h, an aqueous solution of compound 2 was obtained. The product yield was about 95.1% according to liquid phase analysis.

[0056] Preparation of compound 3: The aqueous solution containing compound 2 prepared above was added to a 3L glass reactor. The stirring speed was set to 200 rpm and the reaction temperature was 0℃. 1 mol of 30 wt% hydrogen peroxide aqueous solution was added. After reacting for 5 h, a mixture containing compound 3 was obtained. The product yield was about 90.0% according to liquid phase analysis.

[0057] Preparation of product C10 dialdehyde: The aqueous solution of compound 3 was placed in a 5L three-necked flask, sulfuric acid was added, the pH of the system was adjusted to 3, the reaction temperature was adjusted to 60℃, the reaction pressure to 1.0MPa, the reaction speed to 200rpm, and the reaction was continued for 3h. The reaction was stopped and stirring was stopped. After filtration, the solid product C10 dialdehyde was obtained. After drying, 67.46g of solid was obtained. Liquid phase analysis showed that the purity of the product was about 97.6%, the single-step yield was 97.3%, and the total yield of the series reaction was 80.2%.

[0058] The above demonstrates that the key intermediate C10 dialdehyde can be prepared using a simple 4-step synthesis method with high overall yield, mild reaction conditions, and advantages in the industrial chain.

[0059] Example 2:

[0060] Preparation of compound 1: 1 mol of 142 g of pentanealdehyde was placed in a 1 L three-necked flask. The stirring speed was set to 300 rpm. 280 g of methanol and 1.5 mol of 393.45 g of triphenylphosphine were added, and 1.5 mol of hydrogen bromide was introduced. The system temperature was adjusted to 20 °C and the pressure was adjusted to 2.0 MPa. The reaction was continued for 6 h. After solvent removal, crystals of compound 1 were obtained. The purity of the liquid chromatography was about 99.2%, and the product yield was 96.1%.

[0061] Preparation of compound 2: Compound 1 was dissolved in 850g of deionized water, the stirring speed was set to 200rpm, 2mol of solid sodium bisulfite was added, the system temperature was adjusted to 110℃, the pressure was adjusted to 2.0MPa, and after reacting for 2h, an aqueous solution of compound 2 was obtained. The product yield was about 94.8% according to liquid phase analysis.

[0062] Preparation of compound 3: The aqueous solution containing compound 2 was added to a 3L glass reactor. The stirring speed was set to 300 rpm and the reaction temperature was set to 10℃. 2 mol of 30 wt% hydrogen peroxide aqueous solution was added. After reacting for 6 h, a mixture containing compound 3 was obtained. The product yield was about 89.6% according to liquid phase analysis.

[0063] Preparation of product C10 dialdehyde: The aqueous solution of the above compound 3 was placed in a 5L three-necked flask, sulfuric acid was added, the pH of the system was adjusted to 4, the reaction temperature was adjusted to 70℃, the reaction pressure to 2.0MPa, the reaction speed to 300rpm, and the reaction was continued for 4h. The reaction was stopped and stirring was stopped. After filtration, the solid product C10 dialdehyde was obtained. After drying, 64.71g of solid was obtained. Liquid phase analysis showed that the purity of the product was about 99.1%, the single-step yield was 95.7%, and the total yield of the series reaction was 78.1%.

[0064] Example 3:

[0065] Preparation of compound 1: 1 mol of 142 g of pentanealdehyde was placed in a 1 L three-necked flask. The stirring speed was set to 300 rpm. 420 g of methanol and 2.0 mol of 524.6 g of triphenylphosphine were added, and 2.0 mol of hydrogen bromide was introduced. The system temperature was adjusted to 30 °C and the pressure was adjusted to 3.0 MPa. The reaction was continued for 7 h. After solvent removal, crystals of compound 1 were obtained. The purity of the liquid chromatography was about 98.9%, and the product yield was 96.2%.

[0066] Preparation of compound 2: Dissolve compound 1 in 1700g of deionized water, set the stirring speed to 300rpm, add 3mol of solid sodium bisulfite, adjust the system temperature to 120℃, adjust the pressure to 1.5MPa, and react for 3h to obtain an aqueous solution of compound 2. Liquid phase analysis showed that the product yield was about 94.5%.

[0067] Preparation of compound 3: The aqueous solution containing compound 2 was added to a 3L glass reactor. The stirring speed was set to 400 rpm and the reaction temperature was set to 20℃. 3 mol of 20wt% hydrogen peroxide aqueous solution was added. After reacting for 6 hours, a mixture containing compound 3 was obtained. The product yield was about 90.6% according to liquid phase analysis.

[0068] Preparation of product C10 dialdehyde: The aqueous solution of the above compound 3 was placed in a 5L three-necked flask, sulfuric acid was added, the pH of the system was adjusted to 3, the reaction temperature was adjusted to 80℃, the reaction pressure to 3.0MPa, the reaction speed to 400rpm, and the reaction was continued for 5h. The reaction was stopped and stirring was stopped. After filtration, the solid product C10 dialdehyde was obtained. After drying, 66.25g of solid was obtained. Liquid phase analysis showed that the purity of the product was about 98.9%, the single-step yield was 96.9%, and the total yield of the series reaction was 79.8%.

[0069] Example 4:

[0070] Preparation of compound 1: 1 mol of 142 g of pentanealdehyde was placed in a 3 L three-necked flask. The stirring speed was set to 400 rpm. 600 g of methanol and 3.0 mol of 787 g of triphenylphosphine were added, and 3.0 mol of hydrogen bromide was introduced. The system temperature was adjusted to 40 °C and the pressure was adjusted to 4.0 MPa. The reaction was continued for 8 h. After solvent removal, crystals of compound 1 were obtained. The purity of the liquid chromatography was about 99.2%, and the product yield was 95.9%.

[0071] Preparation of compound 2: Dissolve compound 1 in 2126.5g of deionized water, set the stirring speed to 400rpm, add 5mol of solid sodium bisulfite, adjust the system temperature to 125℃ and the pressure to 2.0MPa, and react for 4h to obtain an aqueous solution of compound 2. Liquid phase analysis showed that the product yield was about 93.6%.

[0072] Preparation of compound 3: The aqueous solution containing compound 2 was added to a 3L glass reactor. The stirring speed was set to 500 rpm and the reaction temperature was set to 25℃. 4 mol of 30 wt% hydrogen peroxide aqueous solution was added. After reacting for 8 hours, a mixture containing compound 3 was obtained. The product yield was about 89.7% according to liquid phase analysis.

[0073] Preparation of product C10 dialdehyde: The aqueous solution of the above compound 3 was placed in a 5L three-necked flask, sulfuric acid was added, the pH of the system was adjusted to 5, the reaction temperature was adjusted to 90℃, the reaction pressure to 5.0MPa, the reaction speed to 500rpm, and the reaction was continued for 7h. The reaction was stopped and stirring was stopped. After filtration, the solid product C10 dialdehyde was obtained. After drying, 163.7g of solid was obtained. Liquid phase analysis showed that the purity of the product was about 99.0%, the single-step yield was 95.4%, and the total yield of the series reaction was 76.81%.

[0074] Example 5:

[0075] Preparation of compound 1: 1 mol of 142 g of pentanealdehyde was placed in a 5 L three-necked flask. The stirring speed was set to 400 rpm. 710 g of methanol and 3.0 mol of 787 g of triphenylphosphine were added, and 3.0 mol of hydrogen bromide was introduced. The system temperature was adjusted to 50 °C and the pressure was adjusted to 5.0 MPa. The reaction was continued for 10 h. After solvent removal, crystals of compound 1 were obtained. The purity of liquid chromatography was about 99.1%, and the product yield was 96.0%.

[0076] Preparation of compound 2: Dissolve compound 1 in 2126.5g of deionized water, set the stirring speed to 500rpm, add 4mol of solid sodium bisulfite, adjust the system temperature to 125℃, adjust the pressure to 2.0MPa, and react for 5h to obtain an aqueous solution of compound 2. Liquid phase analysis showed that the product yield was about 94.1%.

[0077] Preparation of compound 3: The aqueous solution containing compound 2 was added to a 3L glass reactor. The stirring speed was set to 500 rpm and the reaction temperature was set to 30℃. 5 mol of 30 wt% hydrogen peroxide aqueous solution was added. After reacting for 9 h, a mixture containing compound 3 was obtained. The product yield was about 88.3% according to liquid phase analysis.

[0078] Preparation of product C10 dialdehyde: The aqueous solution of the above compound 3 was placed in a 5L three-necked flask, sulfuric acid was added, the pH of the system was adjusted to 5, the reaction temperature was adjusted to 85℃, the reaction pressure to 5.0MPa, the reaction speed to 500rpm, and the reaction was continued for 6h. The reaction was stopped and stirring was stopped. After filtration, the solid product C10 dialdehyde was obtained. After drying, 64.23g of solid was obtained. Liquid phase analysis showed that the purity of the product was about 99.2%, the single-step yield was 97.3%, and the total yield of the series reaction was 77.6%.

Claims

1. A process for the preparation of an aporphine intermediate, characterized in that, The method comprises the following steps: (1) a salt reaction of a five-carbon aldehyde with an organic phosphine in the presence of an acid to form compound 1; (2) an addition reaction of compound 1 under the action of a catalyst to form compound 2; (3) a coupling reaction of compound 2 with a peroxide to form compound 3; (4) a hydrolysis reaction of compound 3 in an acidic environment to form product C10 dialdehyde; The structural formula of the five-carbon aldehyde is: In step (1), the acid is an inorganic acid selected from hydrochloric acid or hydrogen bromide; the organic phosphine is triphenylphosphine; In step (2), the catalyst is an inorganic salt containing hydrogen in the anion, and is selected from one or more of sodium bisulfite or potassium bisulfite; The structure of the compound 1 is: The structure of the compound 2 is: The structure of the compound 3 is: wherein X - is an anion of a mineral acid, and M is a cationic metal in the catalyst; The structure of the C10-dialdehyde is:

2. The production method according to claim 1, characterized by, The molar ratio of the five-carbon aldehyde to the organic phosphine and the acid is 1:(0.5-5.0):(0.5-5.0).

3. The preparation method according to claim 2, characterized in that, The molar ratio of the five-carbon aldehyde to the organic phosphine and the acid is 1:(1-3.0):(1-3.0).

4. The preparation method according to claim 1, characterized in that, The step (1) is carried out in a solvent, and the solvent is one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol, and tert-butanol.

5. The preparation method according to claim 4, characterized in that, The solvent in the step (1) is methanol.

6. The production method according to claim 5, wherein In the step (1), the mass of the solvent added per gram of the five-carbon aldehyde is 0.5-10 g.

7. The preparation method according to claim 6, characterized in that, In the step (1), the mass of the solvent added per gram of the five-carbon aldehyde is 1-5 g.

8. The method of claim 1, wherein, In step (1), the reaction temperature is -20-70°C.

9. The production method according to claim 8, characterized by, In step (1), the reaction temperature is 10-50°C.

10. The method of claim 1, wherein, In step (1), the reaction pressure is 0.01-10.0 MPa.

11. The method of claim 10, wherein, In step (1), the reaction pressure is 0.1-5.0 MPa.

12. The method of claim 1, wherein, In step (1), the reaction time is 1-20 h.

13. The method of claim 12, wherein, In step (1), the reaction time is 5-10 h.

14. The method of claim 1, wherein, In step (1), the reaction is carried out under stirring, and the stirring speed is 100-1000 rpm.

15. The method of claim 14, wherein, In step (1), the stirring speed is 200-500 rpm.

16. The method of claim 1, wherein, In step (2), the catalyst is sodium bisulfite.

17. The method of claim 1, wherein, The reaction of the step (2) is carried out in a solvent, and the solvent is one or more of methanol, ethanol, isopropanol, ethylene glycol, glycerol, tert-butanol, and water.

18. The method of claim 17, wherein, The solvent of the step (2) is water.

19. The method of claim 18, wherein, In the step (2), the mass of the solvent added per gram of compound 1 is 0.2-10 g.

20. The method of claim 19, wherein, In the step (2), the mass of the solvent added per gram of compound 1 is 1-5 g.

21. The method of claim 1, wherein, In the step (2), the molar ratio of the compound 1 to the catalyst is 1:(1-10).

22. The method of claim 21, wherein, In the step (2), the molar ratio of the compound 1 to the catalyst is 1:(1-5).

23. The method of claim 1, wherein, In step (2), the reaction temperature is 80-150°C.

24. The method of claim 23, wherein, In step (2), the reaction temperature is 100-125°C.

25. The method of claim 1, wherein, In step (2), the reaction pressure is 0.1-10.0 MPa.

26. The method of claim 25, wherein, In step (2), the reaction pressure is 1-2.0 MPa.

27. The method of claim 1, wherein, In step (2), the reaction time is 0.5-10 h.

28. The preparation method according to claim 27, characterized in that, In step (2), the reaction time is 1-5 h.

29. The method of claim 1, wherein, The reaction of step (2) is carried out under stirring, and the stirring speed is 50-800 rpm.

30. The method of claim 29, wherein, The reaction of step (2) is carried out under stirring, and the stirring speed is 100-500 rpm.

31. The method of claim 1, wherein, The coupling reaction in step (3) occurs under catalysis of peroxide, which is one or more of hydrogen peroxide, sodium peroxide, potassium peroxide, calcium peroxide and benzoyl peroxide.

32. The method of claim 31, wherein, The peroxide is hydrogen peroxide.

33. The method of claim 32, wherein the method further comprises, The molar ratio of compound 2 to peroxide is 1:(0.1-10).

34. The preparation method according to claim 33, characterized in that, The molar ratio of compound 2 to peroxide is 1:(1-5).

35. The method of claim 1, wherein, The reaction temperature in step (3) is -10-50℃.

36. The preparation method according to claim 35, characterized in that, The reaction temperature in step (3) is 0-30℃.

37. The method of claim 1, wherein, The reaction pressure in step (3) is 0.1-10.0 MPa.

38. The method of claim 37, wherein the method is performed in a single step. The reaction pressure in step (3) is 1.5-4.0 MPa.

39. The method of claim 1, wherein, The reaction time in step (3) is 0.5-12 h.

40. The preparation method according to claim 39, characterized in that, The reaction time in step (3) is 5-9 h.

41. The method of claim 1, wherein, The reaction in step (3) is carried out under stirring, and the stirring speed is 50-800 rpm.

42. The method of claim 41, wherein, The reaction in step (3) is carried out under stirring, and the stirring speed is 200-500 rpm.

43. The method of claim 1, wherein, The acidic environment in step (4) is formed by adding acid compound, which is one or more of sulfuric acid, hydrochloric acid, nitric acid and phosphoric acid, and hydrobromic acid.

44. The method of claim 43, wherein the method further comprises, The acid compound is sulfuric acid.

45. The method of claim 1, wherein, The pH value of the acidic environment is 1-7, not equal to 7.

46. The method of claim 45, wherein, The pH value of the acidic environment is 3-5.

47. The method of claim 1, wherein, The reaction temperature in step (4) is 50-100℃.

48. The method of claim 47, wherein the method is carried out at a temperature of about 20°C to about 30°C. The reaction temperature in step (4) is 60-90℃.

49. The method of claim 1, wherein, The reaction pressure in step (4) is 0.1-10.0 MPa.

50. The method of claim 49, wherein, The reaction pressure in step (4) is 1.0-5.0 MPa.

51. The method of claim 1, wherein, The reaction time in step (4) is 1-10 h.

52. The method of claim 51, wherein, The reaction time in step (4) is 3-7 h.

53. The method of claim 1, wherein, The reaction in step (4) is carried out under stirring, and the stirring speed is 20-800 rpm.

54. The method of claim 53, wherein, The reaction in step (4) is carried out under stirring, and the stirring speed is 100-500 rpm.

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