A kind of preparation method of astaxanthin

Abstract

The present invention discloses a method for preparing astaxanthin. The specific steps are as follows: (1) treating the waste liquid of vitamin A acetate crystallization with a peroxide to generate compound 1; (2) treating compound 1 with an acid to generate a phosphonate 2; (3) treating the phosphonate 2 with a base and a catalyst to generate compound 3; (3) treating compound 3 with an oxidant to generate astaxanthin. The method utilizes the waste liquid of vitamin A acetate crystallization as a resource to produce astaxanthin with higher added value, which not only solves the problem of waste liquid treatment, but also can prepare astaxanthin with a simple synthesis process, thus having good economic benefits.

Description

Technical Field

[0001] The invention belongs to the technical field of carotenoid synthesis, and particularly relates to a method for preparing astaxanthin. Background Art

[0002] Astaxanthin is a ketocarotenoid and the most antioxidant pigment among carotenoids. Its antioxidant function is 500 times that of vitamin E. Astaxanthin can be used in medicine, food, cosmetics, feed additives and other fields. Astaxanthin is a fat-soluble and water-soluble pigment that can be found in marine organisms such as shrimp, crab, salmon, and algae. In industry, it is often prepared by fermentation of Haematococcus pluvialis microorganisms. The astaxanthin obtained has the advantages of good purity and high all-trans content. However, the cultivation of Haematococcus pluvialis and the fermentation process require extremely long time, and the high-precision and cutting-edge production equipment restricts its large-scale commercial development.

[0003] Therefore, from the perspective of chemical synthesis, the use of existing chemical raw materials to generate astaxanthin as a downstream feed additive and other fields has obvious production cost advantages. The chemical synthesis of astaxanthin mainly includes the 2C10+C20 route and the 2C15+C10 route. Among them, many domestic companies have mastered the industrial production technology of the 2C15+C10 route. This route requires expensive C15 raw materials, and a large amount of inorganic acids and alkalis are required in the production process, resulting in huge costs for the treatment of three wastes, and it gradually loses its production advantages. The synthetic selectivity of the C20 phosphine salt intermediate in the 2C10+C20 route is low, and the unit consumption of the product is extremely high, which does not have a cost advantage. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a method for preparing astaxanthin. The method of the present invention can prepare high-added astaxanthin from low-value vitamin A acetate crystallization waste liquid, so that chemically synthesized astaxanthin has certain cost advantages.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A method for preparing astaxanthin comprises the following steps:

[0007] (1) Vitamin A acetate is reacted with peroxide to generate compound 1;

[0008] (2) Compound 1 reacts with an organic phosphine under the action of an acid to generate a phosphine salt 2;

[0009] (3) Phosphate 2 generates compound 3 under the action of base and catalyst;

[0010] (4) Compound 3 generates astaxanthin in the presence of an oxidant. Preferably, in the present invention, vitamin A acetate can be crystallization waste liquid in the production process of vitamin A acetate, and the crystallization waste liquid refers to the waste liquid containing more than 30% of vitamin A acetate, as well as impurities and by-products.

[0011] Preferably, the structural formula of the compound 1 is:

[0012] The peroxide in step (1) of the present invention is selected from one or more of hydrogen peroxide, sodium peroxide, peracetic acid, potassium peroxide, calcium peroxide, etc., preferably calcium peroxide (CaO2); the molar ratio of the vitamin A acetate to the peroxide is 1:(0.01-1.5), preferably 1:(0.1-0.5).

[0013] The step (1) is carried out in a reaction solvent, which is one or more of methanol, ethanol, propylene glycol, ethylene glycol, isopropanol, butanol, octanol or pentanol, preferably ethanol. The mass of the reaction solvent added to each gram of vitamin A acetate is 0.5-50 g, preferably 1-5 g.

[0014] In step (1), the reaction temperature is 0-100°C, preferably 40-70°C.

[0015] In step (1), the reaction pressure is 0-2.5 MpaG, preferably 0.5-1.5 MpaG.

[0016] In step (1), the reaction time is 1-24 h, preferably 5-10 h.

[0017] The acid in step (2) of the present invention is one or more of hydrochloric acid, nitric acid, sulfuric acid, selenic acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, sulfurous acid, and acetic acid, preferably sulfuric acid; the mass percentage of the acid is 1-98wt%, preferably 10-90wt%. The molar ratio of the compound 1 to the acid is 1:(0.01-1.5), preferably 1:(0.1-0.5).

[0018] The step (2) is carried out in a reaction solvent, which is one or more of methanol, ethanol, water, dichloromethane, tetrahydrofuran, etc., preferably water. The mass of the reaction solvent added per gram of compound 1 is 0.5-50 g, preferably 1-5 g.

[0019] The organic phosphine in step (2) of the present invention is an organic phosphine compound with an aromatic group, such as triphenylphosphine, trioctylphosphine, triphenylphosphine chloride and benzyldiadamantanephosphine, etc., preferably triphenylphosphine. The molar ratio of the compound 1 to the organic phosphine compound is 1:1 to 1:5, preferably 1:1.05 to 1:1.3.

[0020] Preferably, the structural formula of the phosphine salt 2 is: Wherein X is Cl, Br, F, I or HSO4, preferably HSO4.

[0021] In step (2), the reaction temperature is 0-80°C, preferably 10-50°C.

[0022] In step (2), the reaction pressure is 0-5.5 MpaG, preferably 1.0-3.5 MpaG.

[0023] In step (2), the reaction time is 0.2-5 h, preferably 1-5 h.

[0024] The base in step (3) of the present invention is one or more of sodium hydroxide, potassium hydroxide, ammonia, sodium carbonate, sodium bicarbonate, sodium methoxide, etc., preferably sodium hydroxide. The catalyst is a supported vanadium oxide, such as vanadium pentoxide supported by silicon dioxide, vanadium pentoxide supported by activated carbon, vanadium pentoxide supported by aluminum trioxide, vanadium pentoxide supported by titanium oxide, preferably vanadium pentoxide supported by silicon dioxide, denoted as V2O5@SiO2. The molar ratio of the phosphine salt 2 to the base is 1:(0.5-10), preferably 1:(1-5), and the mass ratio of the catalyst to the phosphine salt 2 is (0.05-1.0):1, preferably (0.1-0.5):1.

[0025] The step (3) is carried out in a reaction solvent, which is one or more of dichloromethane, ethyl acetate, acetone, toluene, xylene, etc., preferably toluene, and the mass of the reaction solvent added to each gram of the phosphine salt 2 is 0.5-50 g, preferably 1-5 g. The addition of the reaction solvent can extract the reaction product from the aqueous phase into the organic phase, and completely collect the obtained compound 3.

[0026] Preferably, the structural formula of the compound 3 is:

[0027]

[0028] In step (3), the reaction temperature is 30-150°C, preferably 50-100°C.

[0029] In step (3), the reaction pressure is 0-4.0 MPaG, preferably 1.0-3.0 MPaG.

[0030] In step (3), the reaction time is 1-20 h, preferably 5-10 h.

[0031] In step (4) of the present invention, the oxidant is one or more of iodine, oxygen, ozone, sodium chlorate, potassium permanganate, preferably iodine. The molar ratio of the compound 3 to the oxidant is 1:(0.5-10), preferably 1:(1-5).

[0032] The step (4) is carried out in a reaction solvent, which is one or more of water, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, ethyl acetate, etc., preferably dichloromethane. The mass of the reaction solvent added per gram of compound 3 is 0.5-50 g, preferably 1-5 g.

[0033] In step (4), the reaction temperature is -20-50°C, preferably 0-15°C.

[0034] In step (4), the reaction pressure is 0-4.0 MPaG, preferably 1.0-3.0 MPaG.

[0035] In step (4), the reaction time is 1-25 h, preferably 10-18 h.

[0036] The specific synthesis formula is as follows:

[0037]

[0038] The beneficial effects of the present invention are: providing a simple and efficient synthesis process for preparing astaxanthin using vitamin A acetate, which can directly synthesize using vitamin A acetate crystal waste liquid, turning waste into treasure, solving the problem of waste liquid treatment, and preparing astaxanthin by a simple synthesis process, with good economic benefits.

[0039] The reaction route of the present invention is simple to operate, has mild reaction conditions and short steps, and has a high total yield. The reactions are all carried out under normal pressure and the entire reaction process can be completed in one device. The requirements for the reactor are low and the safety is good. Compared with the process of preparing astaxanthin by fermentation, it has a huge experience advantage and is more conducive to industrial production.

[0040] In the following embodiments of the present invention, the content and purity of each component are tested and calculated by the external standard method of high performance liquid chromatograph, and the conversion rate is calculated based on the content of the product; the liquid chromatography conditions are as follows: chromatographic column: Waters XSelectHSS T3, 4.6μm×250mm; injection volume: 2-10μL, fine-tuned according to the sample conditions; column temperature: 40°C; flow rate: 1mL / min; detector: ultraviolet detector (UV), detection wavelength is 254-400nm; mobile phase: acetonitrile / 0.1% phosphoric acid aqueous solution; when measuring the sample, first establish a liquid phase external standard curve with a pure product, and calculate the mass fraction (content) of each test substance based on the linear relationship between concentration and liquid phase peak area. Specific implementation method:

[0041] The reagents used in the present invention, such as methanol, ethanol and other organic solvents, acids and alkali solutions, were purchased from Shanghai Titan Technology Co., Ltd., C10 dialdehyde was purchased from Guangzhou Zhiteqi Co., Ltd. with a purity of 96%, vitamin A acetate crystallization waste liquid (containing 21wt% of all-trans VA acetate, 19wt% of 13-cis VA acetate, 10wt% of trans VA acetate, and a total content of 50wt% of vitamin A acetate, and the rest were heavy component impurities) was purchased from Zhejiang Xinhecheng Co., Ltd., and the supported vanadium-based catalyst was purchased from Clariant Chemical Co., Ltd.

[0042] Embodiment 1:

[0043] Preparation of compound 1: Take 65.7g of vitamin A acetate crystal waste liquid (containing 0.1mol of vitamin A acetate and the remaining 50% are heavy component impurities) at room temperature in a 1L pressure autoclave, add 32.86g of ethanol, stir to dissolve, and then add 0.72g of solid calcium peroxide particles (0.01mol), set the reaction temperature to 40°C, the reaction pressure to 0.5MPaG, react for 5h under stirring to obtain a reaction solution containing compound 1, and after desolventizing, obtain a light yellow liquid compound 1, about 32.73g, with a purity of 99.9%, that is, the reaction yield is 95.0%.

[0044] Preparation of phosphine salt 2: About 0.1 mol of the prepared compound 1 was placed in a 1 L pressure autoclave, 34.5 g of deionized water was added thereto, and after stirring evenly, 28.6 g (0.105 mol) of triphenylphosphine solid particles and a 10 wt% sulfuric acid aqueous solution containing 0.01 mol of sulfuric acid were added to the reactor at one time. The reaction temperature was adjusted to 10°C and the reaction pressure was 1.0 MPaG. The reaction was stirred for 5 h to obtain an aqueous solution of phosphine salt 2. The concentration of the product phosphine salt 2 in the liquid phase analysis solution was calculated to be 96.1%.

[0045] Preparation of compound 3: Take the solution of phosphine salt 2 prepared above into a 1L pressure autoclave, add 4.0g, 0.1mol of sodium hydroxide solid particles, stir to dissolve it completely, then add 6.5g of commercially available V2O5@SiO2 particles and 64.5g of toluene, adjust the reaction temperature to 50°C, the reaction pressure to 3.0MPaG, react for 5h, separate the phases, desolvate the obtained organic phase, and obtain 53.39g of orange liquid with a liquid analysis purity of 98.0% and a reaction yield of 92.1%.

[0046] Preparation of astaxanthin: Take about 0.1 mol of the above compound 3 in a 1L pressure autoclave, add 59g of dichloromethane and 25.4g of iodine, stir evenly, adjust the reaction temperature to 15°C, the reaction pressure to 1.0MPaG, continue the reaction for 10 hours, and the liquid analysis yield of the obtained organic phase is 95%. Remove the solvent and crystallize at low temperature to obtain orange solid particles, which are shown as astaxanthin solid by nuclear magnetic resonance and have a solid purity of 97.8%.

[0047] As can be seen from the above, this process can obtain astaxanthin with only 4 steps of synthesis, and the tandem yield is 80%, which makes the chemical synthesis of astaxanthin have certain cost advantages. The process reaction conditions are mild and the worthless waste liquid can be reused, which has commercial application prospects.

[0048] Embodiment 2:

[0049] Preparation of compound 1: Take 65.7g of vitamin A acetate crystal waste liquid (containing 0.1mol of vitamin A acetate and the remaining 50% are heavy component impurities) at room temperature in a 1L pressure autoclave, add 65.0g of ethanol, stir to dissolve, and then add 1.44g of solid calcium peroxide particles (0.02mol), set the reaction temperature to 50°C, the reaction pressure to 1.5MPaG, react for 6h under stirring to obtain a reaction solution containing compound 1, and after desolventizing, obtain a light yellow liquid compound 1, about 32.68g, with a purity of 99.9%, that is, the reaction yield is 94.8%.

[0050] Preparation of phosphine salt 2: About 0.1 mol of the prepared compound 1 was placed in a 1 L pressure autoclave, 69 g of deionized water was added thereto, and after stirring evenly, 29.92 g (0.11 mol) of triphenylphosphine solid particles and 20 wt% sulfuric acid aqueous solution containing 0.01 mol of sulfuric acid were added to the reactor at one time. The reaction temperature was adjusted to 20°C and the reaction pressure was 1.5 MPaG. The reaction was stirred for 4 h to obtain an aqueous solution of phosphine salt 2. The concentration of the product phosphine salt 2 in the liquid phase analysis solution was calculated to be 96.3%.

[0051] Preparation of compound 3: Take the solution of phosphine salt 2 prepared above (including about 0.1 mol of phosphine salt 2) into a 1L pressure autoclave, add 8.0g, 0.2mol of sodium hydroxide solid particles, stir to dissolve it completely, then add 13.0g of commercially available V2O5@SiO2 particles and 129g of toluene, adjust the reaction temperature to 50°C, the reaction pressure to 2.5MPaG, react for 6h, separate the phases, and desolventize the obtained organic phase to obtain 53.47g of orange liquid with a liquid analysis purity of 98.2% and a reaction yield of 92.3%.

[0052] Preparation of astaxanthin: Take about 0.1 mol of the above compound 3 in a 1L pressure autoclave, add 118 g of dichloromethane and 50.8 g of iodine, stir evenly, adjust the reaction temperature to 10°C, the reaction pressure to 2.0 MPaG, continue the reaction for 13 hours, and the liquid analysis yield of the obtained organic phase is 95.1%. Remove the solvent and crystallize at low temperature to obtain orange solid particles, which are shown as astaxanthin solid by nuclear magnetic resonance and have a solid purity of 97.9%.

[0053] Embodiment 3:

[0054] Preparation of compound 1: Take 65.7g of vitamin A acetate crystal waste liquid (containing 0.1mol of vitamin A acetate and the remaining 50% are heavy component impurities) at room temperature in a 1L pressure autoclave, add 162.5g of ethanol, stir and dissolve, then add 3.60g of solid calcium peroxide particles (0.05mol), set the reaction temperature to 70°C, the reaction pressure to 0.5MPaG, react for 10h under stirring to obtain a reaction solution containing compound 1, and after desolventizing, obtain a light yellow liquid compound 1, about 32.99g, with a purity of 99.9%, that is, the reaction yield is 95.70%.

[0055] Preparation of phosphine salt 2: About 0.1 mol of the prepared compound 1 was placed in a 1L pressure autoclave, 172.5 g of deionized water was added thereto, and after stirring evenly, 35.4 g (0.13 mol) of triphenylphosphine solid particles and 90 wt% sulfuric acid aqueous solution containing 0.05 mol of sulfuric acid were added to the reactor at one time. The reaction temperature was adjusted to 50°C and the reaction pressure was 3.5 MPaG. The reaction was stirred for 1 h to obtain an aqueous solution of phosphine salt 2. The concentration of the product phosphine salt 2 in the liquid phase analysis solution was calculated to be 96.1%.

[0056] Preparation of compound 3: Take the solution of phosphine salt 2 prepared above (including about 0.1 mol of phosphine salt 2) into a 1L pressure autoclave, add 20g, 0.5mol of sodium hydroxide solid particles, stir to dissolve it completely, then add 32.5g of commercially available V2O5@SiO2 particles and 322.5g of toluene, adjust the reaction temperature to 100°C, the reaction pressure to 1.0MPaG, react for 10h, separate the phases, desolvate the obtained organic phase, and obtain 54.58g of orange liquid with a liquid analysis purity of 98.5% and a reaction yield of 94.5%.

[0057] Preparation of astaxanthin: Take about 0.1 mol of the above compound 3 in a 1L pressure autoclave, add 295g of dichloromethane and 127g of iodine, stir evenly, adjust the reaction temperature to 0°C, the reaction pressure to 3.0MPaG, continue the reaction for 18h, and the liquid analysis yield of the obtained organic phase is 95.8%. Remove the solvent and crystallize at low temperature to obtain orange solid particles, which are shown as astaxanthin solid by nuclear magnetic resonance and have a solid purity of 98.2%.

[0058] Embodiment 4:

[0059] Preparation of compound 1: Take 65.7g of vitamin A acetate crystal waste liquid (containing 0.1mol of vitamin A acetate and the remaining 50% are heavy component impurities) at room temperature in a 1L pressure autoclave, add 32.86g of methanol, stir and dissolve, then add 0.72g of calcium peroxide solid particles (0.01mol), set the reaction temperature to 40°C, the reaction pressure to 0.5MPaG, react for 5h under stirring, and obtain a reaction solution containing compound 1. After desolvation, a light yellow liquid compound 1 is obtained, about 32.46g, with a purity of 99.8%, that is, the reaction yield is 94.04%.

[0060] Preparation of phosphine salt 2: About 0.1 mol of the prepared compound 1 was placed in a 1 L pressure autoclave, 34.5 g of deionized tetrahydrofuran was added thereto, and after stirring evenly, 28.6 g (0.105 mol) of triphenylphosphine solid particles and 10 wt% hydrochloric acid aqueous solution containing 0.01 mol HCl were added to the reactor at one time. The reaction temperature was adjusted to 10°C and the reaction pressure was 1.0 MPaG. The reaction was stirred for 5 h to obtain a phosphine salt 2 solution. The concentration of the product phosphine salt 2 in the solution was analyzed by liquid phase analysis, and the reaction yield was calculated to be 95.8%.

[0061] Preparation of compound 3: Take the solution of phosphine salt 2 prepared above (including about 0.1 mol of phosphine salt 2) in a 1L pressure autoclave, add 5.4g, 0.1mol of sodium methoxide, stir to dissolve it completely, then add 6.5g of commercially available V2O5@C particles and 64.5g of ethyl acetate, adjust the reaction temperature to 50°C, the reaction pressure to 3.0MPaG, react for 5h, separate the phases, desolvate the obtained organic phase, and obtain 53.4g of orange liquid with a liquid analysis purity of 98.1% and a reaction yield of 92.2%.

[0062] Preparation of astaxanthin: Take about 0.1 mol of the above compound 3 in a 1L pressure autoclave, add 59g of water and 59g of dichloromethane mixture and 10.65g of sodium chlorate, stir evenly, adjust the reaction temperature to 15°C, the reaction pressure to 1.0MPaG, continue the reaction for 10h, and the liquid analysis yield of the obtained organic phase is 94.8%. Remove the solvent and crystallize at low temperature to obtain orange solid particles, which are shown as astaxanthin solid by nuclear magnetic resonance and have a solid purity of 97.5%.

[0063] Embodiment 5:

[0064] Preparation of compound 1: Take 65.7g of vitamin A acetate crystal waste liquid (containing 0.1mol of vitamin A acetate and the remaining 50% are heavy component impurities) in a 1L pressure autoclave at room temperature, add 164g of methanol, stir and dissolve, then add 3.6g of solid calcium peroxide particles (0.05mol), set the reaction temperature to 70°C, the reaction pressure to 1.5MPaG, react for 10h under stirring, and obtain a reaction solution containing compound 1. After desolvation, a light yellow liquid compound 1 is obtained, about 32.99g, with a purity of 99.7%, that is, the reaction yield is 95.48%.

[0065] Preparation of phosphine salt 2: About 0.1 mol of the prepared compound 1 was placed in a 1 L pressure autoclave, 172.5 g of deionized tetrahydrofuran was added thereto, and after stirring evenly, 35.3 g (0.13 mol) of triphenylphosphine solid particles and 30 wt% hydrochloric acid aqueous solution containing 0.05 mol HCl were added to the reactor at one time. The reaction temperature was adjusted to 50°C and the reaction pressure was 3.5 MPaG. The reaction was stirred for 1 h to obtain a phosphine salt 2 solution. The concentration of the product phosphine salt 2 in the solution was analyzed by liquid phase analysis, and the reaction yield was calculated to be 95.2%.

[0066] Preparation of compound 3: Take the solution of phosphine salt 2 prepared above (including about 0.1 mol of phosphine salt 2) in a 1L pressure autoclave, add 27g, 0.5mol of sodium methoxide, stir to dissolve it completely, then add 32.25g of commercially available V2O5@C particles and 322.5g of ethyl acetate, adjust the reaction temperature to 100°C, the reaction pressure to 1.0MPaG, react for 10h, separate the phases, desolvate the obtained organic phase, and obtain 52.9g of orange liquid with a liquid analysis purity of 98.8% and a reaction yield of 91.9%.

[0067] Preparation of astaxanthin: Take about 0.1 mol of the above compound 3 in a 1L pressure autoclave, add 59g of water and 59g of dichloromethane mixture and 10.65g of sodium chlorate, stir evenly, adjust the reaction temperature to 0°C, the reaction pressure to 3.0MPaG, continue the reaction for 18h, and the liquid analysis yield of the obtained organic phase is 94.4%. Remove the solvent and crystallize at low temperature to obtain orange solid particles, which are shown as astaxanthin solid by nuclear magnetic resonance and have a solid purity of 97.2%.

Claims

1. A method for preparing astaxanthin, characterized in that: The following steps are involved: (1) Vitamin A acetate is reacted with peroxide to generate compound 1; (2) Compound 1 reacts with an organic phosphine under the action of an acid to generate a phosphine salt 2; (3) Phosphate 2 generates compound 3 under the action of base and catalyst; (4) Compound 3 generates astaxanthin in the presence of an oxidant; The organic phosphine in step (2) is triphenylphosphine; The oxidant is one or more of elemental iodine and sodium chlorate; The structural formula of the compound 1 is: The structural formula of the phosphine salt 2 is: Wherein X is Cl, Br, F, I or HSO4; The structural formula of the compound 3 is: The peroxide in step (1) is selected from calcium peroxide; In step (3), the catalyst is selected from vanadium pentoxide supported by silicon dioxide, vanadium pentoxide supported by activated carbon, vanadium pentoxide supported by aluminum oxide, and vanadium pentoxide supported by titanium oxide.

2. The preparation method according to claim 1, characterized in that: Vitamin A acetate adopts the crystallization waste liquid in the production process of vitamin A acetate, and the crystallization waste liquid contains more than 30% of vitamin A acetate.

3. The preparation method according to claim 1, characterized in that: The molar ratio of the vitamin A acetate to the peroxide is 1:(0.01-1.5).

4. The preparation method according to claim 3, characterized in that: The molar ratio of the vitamin A acetate to the peroxide is 1:(0.1-0.5).

5. The preparation method according to claim 1, characterized in that: The step (1) is carried out in a reaction solvent, and the reaction solvent is one or more of methanol, ethanol, propylene glycol, ethylene glycol, isopropanol, butanol, octanol or pentanol.

6. The preparation method according to claim 5, characterized in that: The reaction solvent is ethanol.

7. The preparation method according to claim 1, characterized in that: The mass of the reaction solvent added to each gram of vitamin A acetate is 0.5-50 g.

8. The preparation method according to claim 7, characterized in that: The mass of the reaction solvent added to each gram of vitamin A acetate is 1-5 g.

9. The preparation method according to claim 1, characterized in that: In step (1), the reaction temperature is 0-100°C.

10. The preparation method according to claim 9, characterized in that: In step (1), the reaction temperature is 40-70°C.

11. The preparation method according to claim 1, characterized in that: In step (1), the reaction pressure is 0-2.5 MpaG.

12. The preparation method according to claim 11, characterized in that: In step (1), the reaction pressure is 0.5-1.5 MpaG.

13. The preparation method according to claim 1, characterized in that: In step (1), the reaction time is 1-24h.

14. The preparation method according to claim 13, characterized in that: In step (1), the reaction time is 5-10 hours.

15. The preparation method according to claim 1, characterized in that: The acid in step (2) is one or more of hydrochloric acid, sulfuric acid, hydrofluoric acid and hydrobromic acid.

16. The preparation method according to claim 15, characterized in that: The acid in step (2) is sulfuric acid.

17. The preparation method according to claim 1, characterized in that: The mass percentage of the acid in step (2) is 1-98wt%.

18. The preparation method according to claim 17, characterized in that: The mass percentage of the acid in step (2) is 10-90wt%.

19. The preparation method according to claim 1, characterized in that: The molar ratio of the compound 1 to the acid is 1:(0.01-1.5).

20. The preparation method according to claim 19, characterized in that: The molar ratio of the compound 1 to the acid is 1:(0.1-0.5).

21. The preparation method according to claim 1, characterized in that: The step (2) is carried out in a reaction solvent, and the reaction solvent is one or more of methanol, ethanol, water, dichloromethane, and tetrahydrofuran.

22. The preparation method according to claim 21, characterized in that: The reaction solvent is water.

23. The preparation method according to claim 22, characterized in that: The mass of the reaction solvent added to each gram of compound 1 is 0.5-50 g.

24. The preparation method according to claim 23, characterized in that: The mass of the reaction solvent added to each gram of compound 1 is 1-5 g.

25. The preparation method according to claim 1, characterized in that: The molar ratio of the compound 1 to the organic phosphine compound is 1:1 to 1:

5.

26. The preparation method according to claim 25, characterized in that: The molar ratio of the compound 1 to the organic phosphine compound is 1:1.05 to 1:1.

3.

27. The preparation method according to claim 1, characterized in that: The structural formula of the phosphine salt 2 is: Wherein X is HSO4.

28. The preparation method according to claim 1, characterized in that: In step (2), the reaction temperature is 0-80°C.

29. The preparation method according to claim 28, characterized in that: In step (2), the reaction temperature is 10-50°C.

30. The preparation method according to claim 1, characterized in that: In step (2), the reaction pressure is 0-5.5 MpaG.

31. The preparation method according to claim 30, characterized in that: In step (2), the reaction pressure is 1.0-3.5 MpaG.

32. The preparation method according to claim 1, characterized in that: In step (2), the reaction time is 0.2-5h.

33. The preparation method according to claim 32, characterized in that: In step (2), the reaction time is 1-5h.

34. The preparation method according to claim 1, characterized in that: The alkali in step (3) is one or more of sodium hydroxide, potassium hydroxide, aqueous ammonia, sodium carbonate, sodium bicarbonate, and sodium methoxide.

35. The preparation method according to claim 34, characterized in that: The alkali in step (3) is sodium hydroxide.

36. The preparation method according to claim 35, characterized in that: The catalyst is selected from vanadium pentoxide supported by silicon dioxide, denoted as V2O5@SiO2.

37. The preparation method according to claim 1, characterized in that The molar ratio of the phosphine salt 2 to the base is 1:(0.5-10).

38. The preparation method according to claim 37, characterized in that: The molar ratio of the phosphine salt 2 to the base is 1:(1-5).

39. The preparation method according to claim 1, characterized in that: The mass ratio of the catalyst to the phosphine salt body 2 is (0.05-1.0):

1.

40. The preparation method according to claim 39, characterized in that: The mass ratio of the catalyst to the phosphine salt body 2 is (0.1-0.5):

1.

41. The preparation method according to claim 1, characterized in that The step (3) is carried out in a reaction solvent, and the reaction solvent is one or more of dichloromethane, ethyl acetate, acetone, toluene, and xylene.

42. The preparation method according to claim 41, characterized in that The reaction solvent in step (3) is toluene.

43. The preparation method according to claim 1, characterized in that The mass of the reaction solvent added to each gram of the phosphine salt body 2 is 0.5-50 g.

44. The preparation method according to claim 43, characterized in that: The mass of the reaction solvent added to each gram of the phosphine salt body 2 is 1-5 g.

45. The preparation method according to claim 1, characterized in that: In step (3), the reaction temperature is 30-150°C.

46. ​​The preparation method according to claim 45, characterized in that In step (3), the reaction temperature is 50-100°C.

47. The preparation method according to claim 1, characterized in that In step (3), the reaction pressure is 0-4.0 MPaG.

48. The preparation method according to claim 47, characterized in that In step (3), the reaction pressure is 1.0-3.0 MPaG.

49. The preparation method according to claim 1, characterized in that: In step (3), the reaction time is 1-20h.

50. The preparation method according to claim 49, characterized in that In step (3), the reaction time is 5-10 hours.

51. The preparation method according to claim 1, characterized in that In step (4), the oxidant is elemental iodine.

52. The preparation method according to claim 1, characterized in that In step (4), the molar ratio of the compound 3 to the oxidant is 1:(0.5-10).

53. The preparation method according to claim 52, characterized in that: In step (4), the molar ratio of the compound 3 to the oxidant is 1:(1-5).

54. The preparation method according to claim 1, characterized in that The step (4) is carried out in a reaction solvent, and the reaction solvent is one or more of water, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, and ethyl acetate.

55. The preparation method according to claim 54, characterized in that: The reaction solvent in step (4) is dichloromethane.

56. The preparation method according to claim 1, characterized in that The mass of the reaction solvent added to each gram of compound 3 is 0.5-50 g.

57. The preparation method according to claim 56, characterized in that The mass of the reaction solvent added to each gram of compound 3 is 1-5 g.

58. The preparation method according to claim 1, characterized in that In step (4), the reaction temperature is -20-50°C.

59. The preparation method according to claim 58, characterized in that In step (4), the reaction temperature is 0-15°C.

60. The preparation method according to claim 1, characterized in that In step (4), the reaction pressure is 0-4.0 MPaG.

61. The preparation method according to claim 60, characterized in that: In step (4), the reaction pressure is 1.0-3.0 MPaG.

62. The preparation method according to claim 1, characterized in that In step (4), the reaction time is 1-25h.

63. The preparation method according to claim 62, characterized in that: In step (4), the reaction time is 10-18 hours.

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