A kind of preparation method of canthaxanthin

Abstract

The present invention discloses an efficient and environmentally friendly process for preparing canthaxanthin, wherein beta-carotene is used as a raw material, and an oxidation reaction is carried out under the action of a catalyst to generate a crude canthaxanthin product, wherein the catalyst is an alkaline earth metal oxide modified by a transition metal. Compared with the prior art, the present invention has the following advantages: (1) the process couples the traditional oxidation reaction and the isomerization reaction, and can obtain canthaxanthin crystals in one step, the total yield of oxidation isomerization series is greater than 85%, the total purity of the obtained crystals is greater than 97%, and the total trans content is higher than 92%; (2) compared with the traditional synthesis process, the production capacity of the canthaxanthin obtained by the method is greatly improved; (3) the process is a solvent-free system, and does not use the inorganic salt solution required by the traditional process, and no waste liquid or wastewater is generated, which is green and environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a highly efficient and environmentally friendly method for preparing canthaxanthin. Background Art

[0002] Canthaxanthin is a good colorant and an additive with high application value and economic value. It is currently mainly used as a feed additive, which can make the color of egg yolks and poultry meat brighter and make the color of salmon and trout more ruddy.

[0003] The artificial synthesis of canthaxanthin generally adopts the C40 synthesis method, that is, β-carotene is used as the raw material to undergo an oxidation reaction under the action of a catalyst to obtain canthaxanthin. This route produces canthaxanthin in one step, has simple process steps, and is currently the mainstream industrial route for synthesizing canthaxanthin.

[0004] However, the one-step synthesis of canthaxanthin has the following problems: (1) The oxidation reaction produces a large amount of impurities, resulting in a selectivity of only 75%; (2) The crude canthaxanthin obtained by oxidation needs to be desolvated before undergoing an isomerization reaction, so that 57% of the cis-canthaxanthin in the crude product is converted into all-trans-canthaxanthin, and the process is relatively complicated. (3) Since the solubility of β-carotene and canthaxanthin in organic solvents is relatively low, less than 5%, the oxidation process is often an inorganic salt water oxidation system, so a large amount of solvent and wastewater are generated during the production process. The process is not low-carbon and environmentally friendly, and it is difficult to recover high-salt wastewater and solvents.

[0005] Therefore, it is extremely critical to create a method for synthesizing canthaxanthin with low or no solvent usage, few by-products, high yield and high all-trans content. Summary of the invention

[0006] In order to solve the above problems, the present invention provides a method for preparing canthaxanthin. The process of the present invention is simple, the operation is convenient, and the equipment and labor costs can be saved. The obtained canthaxanthin has high purity and high all-trans content.

[0007] To achieve the above object, the present invention adopts the following technical solution:

[0008] A method for preparing canthaxanthin, which takes beta-carotene as a raw material and generates all-trans canthaxanthin by oxidation reaction under the action of a catalyst.

[0009] The catalyst of the present invention is an alkaline earth metal oxide modified by a transition metal, which is denoted as X / YO.

[0010] Wherein, the transition metal X is a Group VIII element selected from one or more of Fe, Co, Ni, Ru, Pd, Pt, etc., preferably a combination of Fe and Ru, wherein the molar ratio of Fe to Ru in the composition is (0.5-10):1, preferably (1-5):1.

[0011] The metal oxide YO is a Group IIA oxide, such as one or more of BeO, MgO, CaO, BaO and SrO, preferably CaO.

[0012] The solid catalyst is loaded in a fixed bed.

[0013] The present invention uses Group IIA oxides as one of the catalytic components. Since they have a strong ability to promote the combination of carbon-oxygen chemical bonds (C=O), they can efficiently oxidize the carbon in the allylic position into a carbonyl group, thereby quickly achieving the oxidation of β-carotene to canthaxanthin. The transition metal Group VIII elements, especially Fe, are 3d 6 4s 2 , Ru is 4d 7 5s 1 The most suitable hole-electron structure makes it have a strong ability to regulate the dissociation, adsorption and rearrangement of carbon-hydrogen bonds (CH). Therefore, the addition of transition metal group VIII elements makes the catalyst have a strong translocation inhibition ability, so that β-carotene can be oxidized to canthaxanthin in all-trans form, while reducing the formation of cis form, which greatly increases the biological activity of the product.

[0014] Furthermore, the preparation method of the catalyst comprises the following steps:

[0015] The transition metal salt is dissolved in a solvent, a reducing agent is added thereto, and then the solid particles are obtained by reduction and filtration. The solid particles are then added to an alkaline earth metal oxide and fully ground on a ball mill, and then dried to obtain the catalyst X / YO.

[0016] In the present invention, the transition metal salt is nitrate, sulfate, hydrochloride, acetate, etc., preferably acetate and hydrochloride;

[0017] The solvent is one or more of ethanol, methanol, isopropanol, n-butanol and ethyl acetate, preferably ethanol;

[0018] The mass percentage of the dissolved transition metal salt is 1-50wt%, preferably 5-20wt%;

[0019] The molar ratio of the transition metal salt to the alkaline earth metal oxide is (0.01-1):1, preferably (0.1-0.5):1;

[0020] The reducing agent is a borohydride, selected from one or more of sodium borohydride, potassium borohydride and lithium borohydride, preferably sodium borohydride;

[0021] The molar ratio of the total transition metal salt to the reducing agent is (0.01-1):1, preferably (0.1-0.5):1;

[0022] The reduction temperature is 10-90°C, preferably 30-70°C;

[0023] The reduction time is 1-10h, preferably 3-7h;

[0024] Further, the method for preparing canthaxanthin comprises the following steps:

[0025] After β-carotene is melted at high temperature, it is passed through a fixed bed filled with a catalyst at a certain flow rate, temperature and pressure. When the reaction system is stable, the mixed material at the reactor outlet is cooled and quickly filtered to obtain a solid product. The canthaxanthin and its all-trans content in the solid are determined, and the liquid is returned to the raw material for continued recycling.

[0026]

[0027] The temperature of melting the beta-carotene is 180-250° C., preferably 190-200° C.;

[0028] The feeding rate of the beta carotene is 0.001-0.01m 3 / s, preferably 0.002-0.006m3 / s;

[0029] Preferably, the reaction space velocity (based on the volume of β-carotene) is 0.04-20s-1, preferably 0.05-0.2s-1;

[0030] The reaction temperature is 190-500°C, preferably 220-300°C;

[0031] The reaction pressure is 0.01-10.0 MPa, preferably 0.1-5.0 MPa;

[0032] The cooling temperature after the reaction is 180-216°C, preferably 190-205°C;

[0033] The filtration time is 0.5-25s, preferably 5-20s.

[0034] The beneficial effects of the present invention are:

[0035] (1) This process couples the traditional oxidation reaction and the isomerization reaction to obtain canthaxanthin crystals in one step, with a total series yield of >85%, a total purity of more than 97%, and an all-trans content of more than 92%;

[0036] (2) The method of the present invention has a fast reaction rate and a short residence time, thereby improving the production capacity of canthaxanthin. Compared with the traditional synthesis process, the production capacity of canthaxanthin obtained by the method is greatly improved;

[0037] (3) This process is a solvent-free system and does not use the inorganic salt water required by the traditional process. No waste liquid or wastewater is generated, which is green and environmentally friendly. DETAILED DESCRIPTION

[0038] The catalysts used in the present invention were purchased from Shanghai Titan Technology Co., Ltd., and the beta-carotene was purchased from New Hope Co., Ltd. with a purity of 96%.

[0039] In the following examples 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 situation; 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 with the linear relationship between concentration and liquid phase peak area. The analysis of each component in the catalyst is carried out by ion chromatography, and the conditions of ion chromatography analysis are consistent with liquid chromatography.

[0040] Embodiment 1:

[0041] Preparation of catalyst: 0.05 mol of ruthenium acetate and 0.05 mol of ferric chloride (the total amount of transition metal salt is 0.1 mol) are dissolved in ethanol to prepare a transition metal salt solution with a mass fraction of 5 wt%. 1.0 mol of NaBH4 is added thereto at 30°C. After stirring and reducing for 7 hours, the solid is filtered out and added to 1.0 mol of MgO solid. The solution is fully ground on a ball mill and dried to obtain the catalyst, which is recorded as Fe&Ru / MgO.

[0042] Preparation of canthaxanthin: β-carotene was melted at 190°C in a nitrogen atmosphere to form a flowing liquid at a volume flow rate of 0.002 m 3 / s through a fixed bed reactor filled with Fe&Ru / MgO particles at a pressure of 0.1 MPa and a reaction temperature of 220°C, an oxidation reaction occurs, and the reaction volume space velocity is controlled to be 0.2 s -1 After the system stabilized, the reactor outlet was sampled and analyzed, and the conversion rate of the raw material β-carotene was 95.8%, and the selectivity of the product canthaxanthin was 92.2%. The total yield of canthaxanthin was calculated to be 88.3%.

[0043] After analysis, the reactor outlet material is rapidly cooled to 190°C to obtain a solid-liquid mixture, which is rapidly filtered within 5 seconds to separate the solid product canthaxanthin, and the liquid is unreacted β-carotene and other impurities, which are returned to the system for recycling. After the solid is collected, the purity is measured by liquid chromatography to be 97.2%, of which the all-trans content is 92.5%. Under the process of the present invention, almost all of the β-carotene has been converted into all-trans canthaxanthin crystals, and crystals that meet the national standard can be obtained without subsequent separation (the national standard requires the minimum purity of canthaxanthin to be greater than 96%).

[0044] This process makes use of the different melting points of raw materials and products for the first time, and realizes the separation of raw materials and products simply and quickly. The reaction process is a solid-liquid contact reaction, and the system does not involve any organic solvents and inorganic salt water, which is green and environmentally friendly.

[0045] In addition, the residence time of this process is only in the order of seconds. For a specific comparison, compared with the canthaxanthin oxidation process described in the document "Chemical Industry Journal, Vol. 57, No. 5, May 2006, New Process for Canthaxanthin Synthesis, Yang Zehui", the production capacity of canthaxanthin in this process is 1.8 kg / h, which is 3 orders of magnitude higher. Example 2:

[0046] Preparation of catalyst: 0.1 mol of ruthenium acetate and 0.1 mol of ferric chloride (the total amount of transition metal salt is 0.2 mol) are dissolved in methanol to prepare a transition metal salt solution with a mass fraction of 10 wt%. 1.0 mol of NaBH4 is added thereto at 40°C. After stirring and reducing for 6 hours, the solid is filtered out and added to 1.0 mol of MgO solid. The solution is fully ground on a ball mill and dried to obtain the catalyst, which is recorded as Fe&Ru / MgO.

[0047] Preparation of canthaxanthin: β-carotene was melted at 195°C in a nitrogen atmosphere to form a fluid liquid, and passed through a fixed bed reactor filled with Fe&Ru / MgO particles at a pressure of 0.5 MPa and a reaction temperature of 240°C at a volume flow rate of 0.003 m3 / s to undergo an oxidation reaction, and the reaction volume space velocity was controlled to be 0.1 s -1 After the system stabilized, the reactor outlet was sampled and analyzed, and the conversion rate of the raw material β-carotene was 95.6%, and the selectivity of the product canthaxanthin was 90.9%. Based on this, the total yield of canthaxanthin was calculated to be 86.9%.

[0048] After analysis, the reactor outlet material was rapidly cooled to 195°C to obtain a solid-liquid mixture, which was rapidly filtered within 10 seconds to separate the solid product canthaxanthin and the liquid, which was unreacted β-carotene and other impurities, and these liquids were returned to the system for recycling. After the solid was collected, its purity was determined by liquid chromatography to be 96.2%, of which the all-trans content was 92.2%.

[0049] Embodiment 3:

[0050] Preparation of catalyst: 0.2 mol of ruthenium acetate and 0.1 mol of cobalt chloride (the total amount of transition metal salt is 0.3 mol) are dissolved in methanol to prepare a transition metal salt solution with a mass fraction of 10 wt%. 1.0 mol of KBH4 is added thereto at 50°C. After stirring and reducing for 5 hours, the solid is filtered out and added to 1.0 mol of CaO solid. The mixture is fully ground on a ball mill and dried to obtain the catalyst, which is recorded as Co&Ru / CaO.

[0051] Preparation of canthaxanthin: β-carotene was melted at 200°C in a nitrogen atmosphere to form a flowing liquid, and then passed through a fixed bed reactor filled with Co&Ru / CaO particles at a pressure of 1.25MPa and a reaction temperature of 260°C at a volume flow rate of 0.004m3 / s to undergo an oxidation reaction. The reaction volume space velocity was controlled to be 0.06s -1 After the system stabilized, the conversion rate of the raw material β-carotene was 93.2% and the selectivity of the product canthaxanthin was 90.1% after sampling and analysis at the reactor outlet. The total yield of canthaxanthin was calculated to be 84.0%.

[0052] After analysis, the reactor outlet material was rapidly cooled to 195°C to obtain a solid-liquid mixture, which was rapidly filtered within 10 seconds to separate the solid product canthaxanthin and the liquid, which was unreacted β-carotene and other impurities. These liquids were returned to the system for recycling. After the solid was collected, its purity was determined by liquid chromatography to be 96.5%, of which the all-trans content was 90.2%.

[0053] Embodiment 4:

[0054] Preparation of catalyst: 0.2 mol of palladium acetate and 0.1 mol of ferric chloride (the total amount of transition metal salt is 0.3 mol) are dissolved in ethyl acetate to prepare a transition metal salt solution with a mass fraction of 15 wt%. 1.0 mol of KBH4 is added thereto at 60°C. After stirring and reducing for 4 hours, the solid is filtered out and added to 1.0 mol of MgO solid. The solution is fully ground on a ball mill and dried to obtain the catalyst, which is recorded as Fe&Pd / MgO.

[0055] Preparation of canthaxanthin: β-carotene was melted at 210°C in a nitrogen atmosphere to form a fluid liquid, and passed through a fixed bed reactor filled with Fe&Pd / MgO particles at a pressure of 4.5MPa and a reaction temperature of 280°C at a volume flow rate of 0.005m3 / s to cause an oxidation reaction, and the reaction volume space velocity was controlled to be 0.05s -1After the system stabilized, the reactor outlet was sampled and analyzed, and the conversion rate of the raw material β-carotene was 95.0%, and the selectivity of the product canthaxanthin was 90.2%. The total yield of canthaxanthin was calculated to be 85.7%.

[0056] After analysis, the reactor outlet material was rapidly cooled to 200°C to obtain a solid-liquid mixture, which was rapidly filtered within 15 seconds to separate the solid product canthaxanthin and the liquid, which was the unreacted β-carotene and other impurities, and these liquids were returned to the system for recycling. After the solid was collected, its purity was determined by liquid chromatography to be 96.1%, of which the all-trans content was 90.1%.

[0057] Embodiment 5:

[0058] Preparation of catalyst: 0.01 mol of ruthenium acetate and 0.05 mol of ferric chloride (the total amount of transition metal salt is 0.06 mol) are dissolved in ethanol to prepare a transition metal salt solution with a mass fraction of 20 wt%. 0.12 mol of NaBH4 is added thereto at 70°C. After stirring and reducing for 3 hours, the solid is filtered out and added to 0.12 mol of MgO solid. The solution is fully ground on a ball mill and dried to obtain the catalyst, which is recorded as Fe&Ru / MgO.

[0059] Preparation of canthaxanthin: β-carotene was melted at 220°C in a nitrogen atmosphere to form a fluid liquid, and passed through a fixed bed reactor filled with a catalyst at a pressure of 5.0 MPa and a reaction temperature of 220°C at a volume flow rate of 0.005 m3 / s to cause an oxidation reaction, and the reaction volume space velocity was controlled to be 0.05 s -1 After the system stabilized, the reactor outlet was sampled and analyzed, and the conversion rate of the raw material β-carotene was 95.2%, and the selectivity of the product canthaxanthin was 96.6%. The total yield of canthaxanthin was calculated to be 92.5%.

[0060] After analysis, the reactor outlet material was rapidly cooled to 205°C to obtain a solid-liquid mixture, which was rapidly filtered within 20 seconds to separate the solid product canthaxanthin and the liquid, which was unreacted β-carotene and other impurities, and these liquids were returned to the system for recycling. After the solid was collected, its purity was determined by liquid chromatography to be 98.2%, of which the all-trans content was 93.5%.

[0061] Comparative Example 1:

[0062] Prepare a 16.6wt% beta-carotene dichloromethane solution (beta-carotene content is 1.0 mol), add it to the bottom of the reactor at a stirring speed of 100 rpm, add 26.8g of sodium chlorate solid particles as a catalyst, and then add 5% sulfuric acid aqueous solution to adjust the system pH to 5.0. Raise the reactor temperature to 50°C, increase the pressure to 0.144Mpa, and terminate the reaction after keeping warm for 15 hours.

[0063] After analysis, the material was rapidly cooled to -10°C and then filtered and dried. The purity of the crystals obtained by solid liquid phase analysis was 75.0%. After 15 hours of reaction, the conversion rate of β-carotene was 99.9% and the selectivity of canthaxanthin was 75.6%.

[0064] After analysis, the material was rapidly cooled to -10°C and then filtered and dried. The purity of the crystals obtained by solid-liquid analysis was 92.7%, of which the mass content of all-trans-canthaxanthin was 79.8%.

[0065] It can be seen from Comparative Example 1 that the all-trans content in the conventional inorganic salt oxidation system does not meet the standard, a large amount of dichloromethane solvent is used, and the reaction time is at the pilot test level.

[0066] Comparative Example 2:

[0067] Preparation of canthaxanthin: β-carotene was melted at 190°C in a nitrogen atmosphere to form a flowing liquid at a volume flow rate of 0.002 m 3 / s through a fixed bed reactor filled with MgO particles at a pressure of 0.1 MPa and a reaction temperature of 220°C, an oxidation reaction occurs, and the reaction volume space velocity is controlled to be 0.2 s -1 After the system stabilized, the conversion rate of the raw material β-carotene was 94.1% and the selectivity of the product canthaxanthin was 89.4% after sampling and analysis at the reactor outlet. The total yield of canthaxanthin was calculated to be 88.3%.

[0068] After analysis, the reactor outlet material was rapidly cooled to 190°C to obtain a solid-liquid mixture, which was rapidly filtered within 5 seconds to separate the solid product canthaxanthin and the liquid, which was unreacted β-carotene and other impurities. These liquids were returned to the system for recycling. After the solid was collected, its purity was determined by liquid chromatography to be 96.7%, of which the all-trans content was 65.4%.

[0069] It can be seen from Comparative Example 2 that when the reaction is carried out without using a transition metal-modified catalyst, the all-trans content in the obtained canthaxanthin is greatly reduced.

Claims

1. A method for preparing canthaxanthin, characterized in that: Using beta-carotene as raw material, an oxidation reaction occurs under the action of a catalyst to generate all-trans canthaxanthin; The catalyst is an alkaline earth metal oxide modified by a transition metal, denoted as X / YO; The transition metal X is a Group VIII element selected from two or more of Fe, Co, Ni, Ru, Pd and Pt, wherein the transition metal X includes at least one of Ru, Pd and Pt, and the metal oxide YO is selected from one or more of BeO, MgO, CaO, BaO and SrO.

2. The preparation method according to claim 1, characterized in that: The transition metal X is a composition of Fe and Ru, wherein the molar ratio of Fe to Ru in the composition is (0.5-10):

1.

3. The preparation method according to claim 2, characterized in that: The transition metal X is a composition of Fe and Ru, wherein the molar ratio of Fe to Ru in the composition is (1-5):

1.

4. The preparation method according to claim 1, characterized in that: The metal oxide YO is CaO.

5. The preparation method according to claim 1, characterized in that: The preparation method of the catalyst comprises the following steps: The transition metal salt is dissolved in a solvent, a reducing agent is added thereto, and then the solid particles are obtained by filtration. The solid particles are then added to an alkaline earth metal oxide and fully ground on a ball mill. The catalyst X / YO is obtained after drying.

6. The preparation method according to claim 5, characterized in that: The solvent is one or more of ethanol, methanol, isopropanol, n-butanol and ethyl acetate.

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

8. The preparation method according to claim 5, characterized in that: The mass percentage of the dissolved transition metal salt is 1-50wt%.

9. The preparation method according to claim 8, characterized in that: The mass percentage of the dissolved transition metal salt is 5-20wt%.

10. The preparation method according to claim 5, characterized in that: The molar ratio of the transition metal salt to the alkaline earth metal oxide is (0.01-1):

1.

11. The preparation method according to claim 10, characterized in that: The molar ratio of the transition metal salt to the alkaline earth metal oxide is (0.1-0.5):

1.

12. The preparation method according to claim 5, characterized in that: The reducing agent is borohydride.

13. The preparation method according to claim 12, characterized in that: The reducing agent is one or more of sodium borohydride, potassium borohydride and lithium borohydride.

14. The preparation method according to claim 13, characterized in that: The reducing agent is sodium borohydride.

15. The preparation method according to claim 5, characterized in that: The molar ratio of the total transition metal salt to the reducing agent is (0.01-1):

1.

16. The preparation method according to claim 15, characterized in that: The molar ratio of the total transition metal salt to the reducing agent is (0.1-0.5):

1.

17. The preparation method according to claim 5, characterized in that: The reduction temperature is 10-90°C.

18. The preparation method according to claim 17, characterized in that: The reduction temperature is 30-70°C.

19. The preparation method according to claim 5, characterized in that: The reduction time is 1-10h.

20. The preparation method according to claim 19, characterized in that: The reduction time is 3-7h.

21. The preparation method according to any one of claims 1 to 5, characterized in that: The method for preparing canthaxanthin comprises the following steps: After β-carotene is melted at high temperature, it is passed through a fixed bed filled with a catalyst at a certain flow rate, temperature and pressure. When the reaction system is stable, the mixed material at the reactor outlet is cooled and quickly filtered and separated to obtain a solid product. The content of canthaxanthin and its all-trans form in the solid is determined, and the liquid is returned to the raw material for continued recycling.

22. The preparation method according to claim 21, characterized in that: The temperature for melting beta-carotene is 180-250°C.

23. The preparation method according to claim 22, characterized in that: The temperature for melting beta-carotene is 190-200°C.

24. The preparation method according to claim 21, characterized in that: The feeding rate of the beta carotene is 0.001-0.01m 3 / s.

25. The preparation method according to claim 24, characterized in that: The feed rate of the beta carotene is 0.002-0.006m 3 / s.

26. The preparation method according to claim 21, characterized in that: Based on the volume of β-carotene, the reaction space velocity is 0.04-20s -1 .

27. The preparation method according to claim 26, characterized in that: Based on the volume of β-carotene, the reaction space velocity is 0.05-0.2s -1 .

28. The preparation method according to claim 21, characterized in that: The reaction temperature is 190-500°C.

29. The preparation method according to claim 28, characterized in that: The reaction temperature is 220-300°C.

30. The preparation method according to claim 21, characterized in that: The reaction pressure is 0.01~10.0MPa.

31. The preparation method according to claim 30, characterized in that: The reaction pressure is 0.1~5.0MPa.

32. The preparation method according to claim 21, characterized in that: The cooling temperature after the reaction is 180-216°C.

33. The preparation method according to claim 32, characterized in that: The cooling temperature after the reaction is 190-205°C.

34. The preparation method according to claim 21, characterized in that: The filtering time is 0.5-25s.

35. The preparation method according to claim 34, characterized in that: The filtering time is 5-20s.

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