Catalyst, preparation method and application of β-carotene oxidative preparation of canthaxanthin

Abstract

The present invention provides a tetraazacyclododecane tetraacetic acid metal catalyst that can be used to oxidize β-carotene to canthaxanthin using hydrogen peroxide as an oxidant. This process provides mild conditions, high product yield, and high selectivity for the all-trans isomer. Furthermore, the catalyst has the advantages of low toxicity, minimal environmental pollution, and recyclability.

Description

Technical Field

[0001] The invention belongs to the field of canthaxanthin, and relates to a catalyst for preparing canthaxanthin by oxidizing beta-carotene and a preparation method, as well as a specific application of the catalyst in preparing canthaxanthin by oxidizing beta-carotene. Background Art

[0002] Canthaxanthin, also known as canthaxanthin, is a carotenoid. Natural canthaxanthin is found in protein-rich foods such as mushrooms, crustaceans, fish, and eggs. Chemically synthesized canthaxanthin, due to its low production cost, high content, and stable production, has gradually replaced natural extraction and biofermentation methods for producing canthaxanthin. Canthaxanthin also has anti-aging, anti-cancer, and cardiovascular disease-preventing properties. In animal feed additives for aquaculture and poultry farming, canthaxanthin can also enhance the appearance of animals and eggs.

[0003] The 1977 patent US4212827A reported a method for synthesizing canthaxanthin, and the reaction equation is as follows: Joachim Paust et al. used highly toxic elemental iodine as a catalyst and hypohalite as an oxidant to oxidize β-carotene to canthaxanthin.

[0004]

[0005] Patent CN1277191 in 2000 uses alkali metal chlorate or alkali metal bromate as an oxidant, and adds iodine halide, iodine or metal iodide as a co-catalyst to oxidize β-carotene to canthaxanthin. This method still requires the use of highly toxic elemental iodine or iodine halide.

[0006] Patent CN1793098 in 2006 disclosed that canthaxanthin can be prepared by irradiating β-carotene with 200-800W light in an oxidant aqueous solution with a pH of 2-5.

[0007] Patent CN101633633, issued in 2010, uses a mixture of alkali metal chlorates or alkali metal bromates, with the addition of catalytic amounts of hydrogen peroxide and metal iodides, to oxidize β-carotene to canthaxanthin. This method can achieve a yield of 78%, but the wastewater generated by the reaction is difficult to treat during the production process.

[0008] The 2021 patent CN113117756A uses phosphorus-doped graphite phase carbon nitride-loaded metal porphyrin complex as a catalyst and hydrogen peroxide as an oxidant to prepare xanthocyanin, and the product and selectivity yields can reach more than 99%; however, highly toxic melamine is used in the catalyst preparation process, which is unfriendly to the environment and operation.

[0009] In summary, in the current process of oxidizing β-carotene to prepare canthaxanthin, elemental iodine and metal iodide catalysts cause serious environmental pollution and increase the cost of wastewater treatment. Therefore, a canthaxanthin preparation method needs to be developed to solve the above problems. Summary of the Invention

[0010] To address the problems existing in the current process of synthesizing canthaxanthin by oxidizing β-carotene, the present invention provides a catalyst for oxidizing β-carotene. The catalyst is a heme-like tetranitrogen metal catalyst with the advantages of high catalytic activity, low toxicity, simple preparation, and recyclability.

[0011] In addition, the present invention also provides the use of the catalyst in oxidizing beta-carotene to prepare canthaxanthin. The method has mild reaction conditions, simple post-treatment, low toxicity, and easy catalyst recovery.

[0012] To achieve the above object, the technical solutions adopted by the present invention are as follows:

[0013] A tetraazacyclododecane tetraacetic acid metal complex can be represented by the following structural formula:

[0014]

[0015] Wherein, the metal M is selected from manganese, iron, nickel, zinc, copper, more preferably manganese;

[0016] The ligand is selected from DOTA, DOTA-NHS, and DOTA-NHS is more preferred. Preferred In this structure, R is -H, which is DOTA, and R is That is DOTA-NHS.

[0017] The present invention also provides a method for preparing the tetraazacyclododecane tetraacetic acid metal complex, comprising the steps of:

[0018] The ligand and metal triflate (M(OTf)2) are dispersed in acetonitrile, stirred at 0-100°C, preferably 20-40°C, for 1-30 hours, preferably 5-10 hours, filtered, spin-dried, crystallized, and dried to obtain a catalyst;

[0019] In the catalyst preparation method of the present invention, the molar ratio of the ligand to the metal triflate is 1:1-100, preferably 1:1-20;

[0020] In the catalyst preparation method of the present invention, the mass ratio of the ligand to acetonitrile is 1:2-10, preferably 1:3-6;

[0021] In the catalyst preparation method of the present invention, the crystallization solvent is selected from one or more of diethyl ether, dimethyl ether, methyl tert-butyl ether and petroleum ether, preferably diethyl ether.

[0022] The invention provides a method for preparing canthaxanthin by oxidizing beta-carotene. The method uses the tetraazacyclododecane tetraacetic acid metal complex as a catalyst.

[0023] A method for preparing canthaxanthin by oxidizing β-carotene, comprising dissolving β-carotene in a solvent and conducting an oxidation reaction in the presence of a catalyst and an oxidant to prepare canthaxanthin;

[0024] In the method of the present invention, the mass ratio of β-carotene to catalyst is 1:0.1-0.3, preferably 1:0.15-0.25;

[0025] In the method of the present invention, the solvent is selected from one or more of dichloromethane, acetone, acetonitrile, n-hexane, and toluene, preferably acetonitrile;

[0026] In the method of the present invention, the solvent is 5-30 times, preferably 6 times, the mass of β-carotene;

[0027] In the method of the present invention, the oxidant is hydrogen peroxide, and the amount used is 10-30 times, preferably 12-15 times, the molar amount of carotene;

[0028] In the method of the present invention, the oxidation reaction temperature is preferably 25-30°C;

[0029] In the method of the present invention, the reaction time is 2-50 hours, preferably 10-15 hours.

[0030] The beneficial effects of the present invention are:

[0031] In the method of the present invention, a DOTO-metal catalyst is constructed and applied to the oxidation of β-carotene to prepare canthaxanthin, thereby improving the reaction efficiency, avoiding the use of elemental iodine and iodine halide catalysts during the reaction process, and preparing canthaxanthin in an efficient and green manner. DETAILED DESCRIPTION

[0032] The present invention will be further described below through specific examples. The examples of the present invention are only for illustration of the present invention and do not limit the scope of the present invention.

[0033] β-Carotene was purchased from DSM;

[0034] Tetraazacyclododecane tetraacetic acid was purchased from Xi'an Qiyue Biotechnology Co., Ltd.;

[0035] The remaining raw materials, unless otherwise specified, were purchased from Aladdin Reagent Network.

[0036] Liquid chromatography analysis conditions: Chromatographic model: Agilent 1260; Chromatographic column: C30 column YMC carotenoid S-

[0037] 5um (4.6*250nm); mobile phase: A: acetonitrile, B: isopropanol; column temperature: 40℃; flow rate: 1.0mL / min; injection volume: 5μL; detection wavelength: 255nm.

[0038] Example 1

[0039] Preparation of catalyst a

[0040] 7.5 g of manganese powder was placed in a 100 mL round-bottom flask. 30 mL of trifluoromethanesulfonic acid was added to a beaker containing 150 mL of distilled water and cooled to room temperature. The prepared trifluoromethanesulfonic acid aqueous solution was slowly added dropwise to the round-bottom flask containing the manganese powder with stirring at a rate of approximately 1 drop per second. After reacting for 1 hour, the liquid was filtered, concentrated, recrystallized from ether, and dried to obtain a white solid in a yield of 98.7%.

[0041] 10 g of the ligand DOTA was placed in a round-bottom flask, and 50 g of acetonitrile was added to dissolve the ligand. 14 g of manganese trifluoromethanesulfonate was added, stirred, and reacted at room temperature for 8 h. After the reaction, the mixture was filtered, dried, and recrystallized from ether. DOTA-manganese trifluoromethanesulfonate was obtained as a white solid in a yield of 99.8%.

[0042] Example 2

[0043] Preparation of catalyst b

[0044] 7.5 g of manganese powder was placed in a 100 mL round-bottom flask. 30 mL of trifluoromethanesulfonic acid was added to a beaker containing 150 mL of distilled water and cooled to room temperature. The prepared trifluoromethanesulfonic acid aqueous solution was slowly added dropwise to the round-bottom flask containing the manganese powder with stirring at a rate of approximately 1 drop per second. After reacting for 1 hour, the liquid was filtered, concentrated, recrystallized from ether, and dried to obtain a white solid.

[0045] 12.5 g of the ligand DOTA-NHS was placed in a round-bottom flask, and 50 g of acetonitrile was added to dissolve the ligand. 14 g of manganese trifluoromethanesulfonate was added, stirred, and reacted at room temperature for 8 h. After the reaction, the mixture was filtered, dried, recrystallized from ether, and dried to obtain DOTA-NHS manganese trifluoromethanesulfonate as a white solid in a yield of 99.9%.

[0046] Example 3

[0047] Preparation of catalyst c

[0048] 7.5 g of copper powder was placed in a 100 mL round-bottom flask. 30 mL of trifluoromethanesulfonic acid was added to a beaker containing 150 mL of distilled water and cooled to room temperature. The prepared trifluoromethanesulfonic acid aqueous solution was slowly added dropwise to the round-bottom flask containing the copper powder with stirring at a rate of approximately 1 drop per second. After reacting for 1 hour, the liquid was filtered, concentrated, recrystallized from ether, and dried to obtain a blue solid in a yield of 98.9%.

[0049] 10 g of the ligand DOTA was placed in a round-bottom flask, and 50 g of acetonitrile was added to dissolve the ligand; 14.5 g of copper trifluoromethanesulfonate was added, stirred, and reacted for 8 h. After the reaction was completed, the mixture was spin-dried, recrystallized from ether, and dried to obtain DOTA-copper trifluoromethanesulfonate solid with a yield of 99.9%.

[0050] Example 4

[0051] Preparation of Canthaxanthin by Oxidation of β-Carotene

[0052] 53.56g of β-carotene (0.1mol) and 8g of catalyst a were placed in a three-necked flask and mixed with 321g of acetonitrile. The mixture was cooled to 5°C and slowly added dropwise with 170g (1.5mol) of 30% hydrogen peroxide. The reaction was allowed to complete after 15h at 25°C. Sodium sulfite was added to quench the mixture, the catalyst was filtered out, and the mixture was separated. After washing with water, HPLC analysis revealed a conversion rate of 99.2%. The mixture was spin-dried and recrystallized from ethanol to obtain 56.26g of canthaxanthin crystals (99.7% all-trans content), a yield of 99.6%.

[0053] After the reaction was completed, the filter cake obtained by filtration was washed with 10 g of n-hexane, dried in an oven, and used as a recovered catalyst for the preparation of canthaxanthin in this example. The experimental data are shown in the following table:

[0054]

[0055]

[0056] Example 5

[0057] Preparation of Canthaxanthin by Oxidation of β-Carotene

[0058] The operation was the same as in Example 4, using catalyst b to catalyze the preparation of canthaxanthin. The relationship between the number of applications and the yield is shown in the following table:

[0059]

[0060] Example 6

[0061] Preparation of Canthaxanthin by Oxidation of β-Carotene

[0062] The operation was the same as in Example 4, using catalyst C to catalyze the preparation of canthaxanthin. The relationship between the number of applications and the yield is shown in the following table:

[0063]

[0064]

[0065] The above specific embodiments do not limit the technical solutions of the present invention in any form. Any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention fall within the scope of protection of the present invention.

Claims

1. A method for preparing canthaxanthin by oxidizing β-carotene, comprising: β-carotene is dissolved in a solvent and subjected to an oxidation reaction in the presence of a catalyst and an oxidant to prepare canthaxanthin; the catalyst is a tetraazacyclododecane tetraacetic acid metal complex, and the structural formula is as follows: Wherein, the metal M is selected from manganese, iron, nickel, zinc, copper, Where R is -H or 2. The method according to claim 1, wherein The mass ratio of the beta-carotene to the catalyst is 1:0.1-0.

3.

3. The method according to claim 1, wherein The mass ratio of the beta-carotene to the catalyst is 1:0.15-0.

25.

4. The method according to claim 1, wherein The solvent is selected from one or more of dichloromethane, acetone, acetonitrile, n-hexane and toluene.

5. The method according to claim 1, wherein The oxidant is hydrogen peroxide.

6. The method according to claim 1 or 5, wherein: The amount of the oxidant used is 10-30 times the molar amount of carotene.

7. The method according to claim 1, wherein The oxidation reaction temperature is 25-30°C; the reaction time is 2-50h.

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