Preparation method of all-trans beta-carotene

Abstract

The present invention discloses a method for preparing all-trans β-carotene. Specifically, the present invention discloses a method for preparing all-trans β-carotene, which is method 1 or method 2: Method 1: It comprises the following steps: In a solvent, under the action of microwaves, a compound as shown in formula I and a solid-supported vitamin A ylide as shown in formula II undergo Wittig reaction to prepare all-trans β-carotene as shown in formula III, that is, Scheme 2: It comprises the following steps: In a solvent, under the action of an oxidant and microwaves, a solid-supported vitamin A ylide as shown in formula II undergoes an oxidative coupling reaction to prepare all-trans β-carotene as shown in formula III, that is, wherein the solid-supported vitamin A ylide as shown in formula II is in triphenylphosphine resin. The preparation method of all-trans β-carotene according to the present invention can achieve one or more of the following effects: high yield, high purity and short reaction time.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for preparing all-trans beta-carotene. Background Art

[0002] The structure of beta-carotene is as follows:

[0003]

[0004] β-carotene is a precursor of vitamin A and can be converted into vitamin A in the human body. The physiological functions and uses of carotene are as follows: maintaining the integrity of the skin and mucous membranes to prevent dry and rough skin; constituting photosensitive substances in visual cells, promoting visual function, preventing night blindness and eye diseases; promoting growth and development, effectively promoting health and cell development, and preventing congenital deficiencies; maintaining reproductive function; maintaining and promoting immune function; as an antioxidant, protecting plant and human cells from damage by free radicals and ultraviolet rays; may have the effect of preventing and inhibiting cancers such as lung cancer and prostate cancer; may have the effect of improving cognitive function. At the same time, in the food and beverage industry, carotene is also widely used in product color enhancement and nutritional fortification, and the demand is large. However, natural carotene is mainly found in yellow, orange or red fruits and vegetables, such as carrots, sweet potatoes, wolfberries, cantaloupes, mangoes, apricots and persimmons. It is difficult to separate and extract natural carotene, so chemical synthesis is required for its preparation. However, due to its long-chain conjugated double bond structure, β-carotene has a large number of cis and trans isomers, and different isomers have different physical and chemical properties. Among them, the thermal stability and chemical stability of the all-trans isomer are better than those of other cis isomers. In terms of nutritional value, the activity of 13-cis and 9-cis isomers of β-carotene is 53% and 38% of that of the all-trans, respectively. And the bioavailability of the all-trans isomer is also higher than that of the cis isomer. Therefore, in the process of producing β-carotene, preparing β-carotene into the all-trans isomer as much as possible is an effective way to maintain its biological efficacy. The current synthetic routes are mainly the following:

[0005] Route 1: 15+10+15 phosphine ester method

[0006]

[0007] US4916250 reported the 2C15+C10 route, in which two molecules of 15-carbon phospholipids and 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde (10-carbon dialdehyde) were subjected to the Wittig-Horner reaction to obtain β-carotene. However, this method requires the use of a stronger base such as sodium hydride or potassium tert-butoxide, and the overall yield is low. The byproduct diethyl phosphate salt is difficult to recover by washing with water, and the processing cost is high. The preparation of all-trans β-carotene requires a second transposition, which takes a long time, and the preparation steps of the raw material 10-carbon dialdehyde are long.

[0008] Route 2: 15+10+15 phosphine salt method

[0009]

[0010] Examples of this method include patents US2006106257A1 and US5689022, both of which use pentadecanedaphosphine salts for preparation. Compared with the phosphine ester process, the advantages of this reaction are mild reaction conditions and the by-product triphenylphosphine oxide can be recycled, but additional transposition operations are still unavoidable and the reaction cycle is long. At the same time, the raw material triphenylphosphine and the by-product triphenylphosphine oxide are difficult to completely remove from the product by simple crystallization. As a nutritional fortification substance and food coloring, the presence of such substances is potentially harmful to users.

[0011] CN 108752251A improves the method and solves the selectivity problem of preparing β-carotene using pentadecanphosphine salt and decacarbon dialdehyde and the filtering problem of triphenylphosphine oxide. The reaction solvent ionic liquid needs to be synthesized, and the residual amount of triphenylphosphine oxide is not mentioned. At the same time, the reaction time is still relatively long.

[0012] Route 3: 20+20 method

[0013]

[0014] Patent CN 101081829A reports that vitamin A is used as a starting material, vitamin A acetate, triphenylphosphine and acid are used to prepare vitamin A phosphonate, and then the phosphonate is used to prepare phosphorus ylide under the action of an oxidant to obtain β-carotene after Wittig reaction. If finished vitamin A is used as a raw material, the cost is high. However, the patent mentions the use of vitamin A crystallization mother liquor containing less than 50% trans-vitamin A to turn the mother liquor into treasure. However, due to the excessive amount of cis-vitamin A in the mother liquor, the proportion of cis-carotene prepared is increased, and a long time is required for transposition. The yield does not exceed 55%, and the problem of triphenylphosphine oxide residues still cannot be solved.

[0015] In order to solve the problem of triphenylphosphine residue in the Wittig reaction, chemists have proposed many solutions, such as the method described in J.Org.Chem.2017,82,19,9931-9936, which uses zinc chloride complex co-precipitation and filtering to remove triphenylphosphine in a polar solvent. Similar solutions include J.Inorg.Nucl.Chem.1963,25,637-640 and Org.Process.Res.Dev.2022,26,1845-1853. Although a large amount of triphenylphosphine can be removed by co-precipitation of metal halides, no solution is proposed for trace residues (<1%), and a large amount of waste salt is generated, increasing the processing cost.

[0016] In summary, the existing methods for preparing all-trans β-carotene have the following problems: the triphenylphosphine used in the reaction and the by-product triphenylphosphine oxide are difficult to completely remove, and the condensation method is time-consuming, produces a large amount of cis-product, and requires an additional transposition step, which reduces the yield. Therefore, it is necessary to seek an environmentally friendly and high-yield method for preparing all-trans β-carotene. Summary of the invention

[0017] The technical problem to be solved by the present invention is to overcome the problems of low yield, low purity or long reaction time in the preparation of all-trans β-carotene in the prior art, and to provide a new preparation method of all-trans β-carotene. The preparation method of all-trans β-carotene described in the present invention can achieve one or more of the following effects: high yield, high purity and short reaction time.

[0018] The present invention solves the above technical problems through the following methods.

[0019] The present invention uses a solid triphenylphosphine resin, which prevents incompletely reacted trivalent phosphine and reaction byproduct pentavalent phosphine from mixing into the product, causing separation difficulties, and improves purity and yield; the present invention adopts microwave reaction, which significantly reduces reaction time and improves reaction yield; preferably, microwaves can provide enough energy to overcome the energy barrier of cis-trans conversion, so that double bond transposition proceeds quickly, and a uniform thermodynamically controlled product, all-trans beta-carotene, is produced; after the reaction is completed, the triphenylphosphine oxide resin obtained after the carotene is dissociated is reacted with a reducing agent to obtain the triphenylphosphine resin, which can then be used continuously.

[0020] The present invention provides a method for preparing all-trans β-carotene, which is the following method 1 or method 2:

[0021] Method 1: It comprises the following steps: In a solvent, under the action of microwaves, the compound shown in formula I and the immobilized vitamin A ylide shown in formula II undergo Wittig reaction as shown below to prepare all-trans β-carotene shown in formula III, that is,

[0022]

[0023] Scheme 2: It comprises the following steps: in a solvent, under the action of an oxidant and microwaves, the immobilized vitamin A ylide shown in formula II undergoes an oxidative coupling reaction as shown below to prepare all-trans β-carotene as shown in formula III, that is,

[0024]

[0025] Wherein, in the immobilized vitamin A ylide as shown in formula II, Triphenylphosphine resin In The CAS number of the triphenylphosphine resin is 39319-11-4.

[0026] It should be understood that the immobilized vitamin A ylide shown in formula II above only represents the loading of The resin having the ylide structure shown is not limited in the number of ylide structures supported thereon.

[0027] The reaction operation and reaction conditions of the Wittig reaction are conventional reaction operations and reaction conditions for such reactions in the art.

[0028] Preferably, in the Wittig reaction or the oxidative coupling reaction, the immobilized vitamin A ylide as shown in formula II is

[0029] Preferably, the Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the reference, and the setting power of the microwave reactor is 5-10 W / mmol, such as 6-8.3 W / mmol, and further such as 6.7 W / mmol.

[0030] Preferably, the Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent of vitamin A derivative, the set power of the microwave reactor is 15 to 30 W / g, preferably 18 to 25 W / g, and more preferably 20 W / g.

[0031] Preferably, the oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the reference, and the setting power of the microwave reactor is 2.7-5 W / mmol, for example 3.3 W / mmol.

[0032] Preferably, the oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent of vitamin A derivative, the set power of the microwave reactor is 8-15 W / g, preferably 10 W / g.

[0033] In any of the above schemes, the vitamin A derivative may be compound V as shown below:

[0034] R is hydrogen, -C(=O)-(C1-C6 alkyl) or palmitoyl.

[0035] Preferably, in said R, said "C1-C6 alkyl" is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, such as methyl or ethyl, preferably methyl.

[0036] Preferably, R is hydrogen, acetyl, propionyl or palmitoyl, such as acetyl.

[0037] Preferably, in the Wittig reaction or the oxidative coupling reaction, the frequency of the microwave is 2000-3000 MHz, for example, 2450 MHz.

[0038] Preferably, the reaction time of the Wittig reaction or the oxidative coupling reaction is 1 to 10 min, preferably 2 to 5 min, for example 3 min.

[0039] Preferably, the Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the reference, the setting power of the microwave reactor is 6-8.3 W / mmol, and the reaction time of the reaction is 2-5 min.

[0040] Preferably, the Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent of vitamin A derivative, the set power of the microwave reactor is 18 to 25 W / g, and the reaction time of the reaction is 2 to 5 minutes.

[0041] Preferably, the oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the reference, the setting power of the microwave reactor is 2.7-5 W / mmol, and the reaction time of the reaction is 2-5 min.

[0042] Preferably, the oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the benchmark, the set power of the microwave reactor is 8-15 W / g, and the reaction time of the reaction is 2-5 min.

[0043] Preferably, in the Wittig reaction, the solvent is water and / or an alcohol solvent, preferably an alcohol solvent, and the alcohol solvent is, for example, methanol and / or ethanol, further example, methanol.

[0044] Preferably, in the Wittig reaction, the mass ratio of the solvent to the compound as shown in Formula I is (3-8):1, for example 5.3:1.

[0045] Preferably, in the Wittig reaction, the compound of formula I and the immobilized vitamin A ylide of formula II The equivalent ratio is (1-1.2):1, for example 1:1 or 1.1:1.

[0046] Preferably, in the oxidative coupling reaction, the solvent is water and / or an alcohol solvent, preferably water, and the alcohol solvent is, for example, methanol and / or ethanol, further example, methanol.

[0047] Preferably, in the oxidative coupling reaction, the solvent and the immobilized vitamin A ylide as shown in formula II The mass equivalent ratio is 0.5 to 1.5 g / mmol, for example 0.8 g / mmol.

[0048] Preferably, in the oxidative coupling reaction, the oxidant is hydrogen peroxide, such as hydrogen peroxide with a mass fraction of 10% to 50%, and further such as hydrogen peroxide with a mass fraction of 30%.

[0049] Preferably, in the oxidative coupling reaction, the oxidant and the immobilized vitamin A ylide as shown in formula II The equivalent ratio is (0.3 to 1.5):1, preferably (0.8 to 1.3):1, for example (1 to 1.3):1, and further example is 1.3:1.

[0050] Preferably, the Wittig reaction or the oxidative coupling reaction is carried out in an inert gas, such as nitrogen.

[0051] After the Wittig reaction is completed, post-treatment is performed through the following steps, which include: filtering and concentrating.

[0052] Preferably, in the Wittig reaction post-treatment step, cooling is performed before the filtration.

[0053] Preferably, the Wittig reaction post-treatment step further comprises the following steps: washing the filtered filter cake with an organic solvent to obtain a washing liquid, and concentrating it; or washing the washing liquid with water to obtain an organic phase, and then concentrating it; the organic solvent can be selected from one or more of a halogenated alkane solvent, an aromatic hydrocarbon solvent, a hydrocarbon solvent, a ketone solvent and an alcohol solvent, preferably a halogenated alkane solvent, the halogenated alkane solvent can be dichloromethane or chloroform, such as dichloromethane, the aromatic hydrocarbon solvent can be toluene or xylene, the hydrocarbon solvent can be heptane, the ketone solvent can be acetone, and the alcohol solvent can be methanol or ethanol.

[0054] After the oxidative coupling reaction is completed, the post-treatment can be carried out by the following steps, which include: mixing with a water-insoluble organic solvent, filtering, and concentrating the organic phase in the filtrate, wherein the water-insoluble organic solvent can be selected from one or more of a halogenated alkane solvent, an aromatic hydrocarbon solvent, and a hydrocarbon solvent, preferably a halogenated alkane solvent, the halogenated alkane solvent can be dichloromethane or chloroform, preferably dichloromethane, the aromatic hydrocarbon solvent can be toluene or xylene, and the hydrocarbon solvent can be heptane. Preferably, after the oxidative coupling reaction is completed, the temperature is first lowered before mixing with the water-insoluble organic solvent.

[0055] Preferably, in the post-treatment steps of the Wittig reaction and the oxidative coupling reaction, the temperature during any concentration is 25-35°C, such as 30°C.

[0056] Preferably, in the post-treatment step of the Wittig reaction or the oxidative coupling reaction, after the filtration, a filter cake is retained, and the filter cake comprises The filter cake is recorded as compound 1, and the filter cake can be post-treated by the following steps, which include: in the case of an organic solvent or in the absence of a solvent, under the action of a reducing agent, the filter cake is subjected to the following reduction reaction to prepare compound 2, that is,

[0057]

[0058] The reaction operation and reaction conditions of the reduction reaction are conventional reaction operations and reaction conditions of this type of reaction in the art.

[0059] Preferably, the reduction reaction is carried out in the presence of an organic solvent.

[0060] When the reduction reaction is carried out in the presence of an organic solvent, the organic solvent may be selected from one or more of a halogenated alkane solvent, a benzene solvent, a hydrocarbon solvent, an alcohol solvent and a cyclic hydrocarbon solvent, preferably a hydrocarbon solvent, the halogenated alkane solvent is preferably dichloromethane, the benzene solvent is preferably toluene, the hydrocarbon solvent is preferably n-heptane or n-hexane, such as n-heptane, the alcohol solvent is preferably ethanol, and the cyclic hydrocarbon solvent is preferably cyclohexane.

[0061] When the reduction reaction is carried out in the presence of an organic solvent, the organic solvent and the compound 1 The mass molar ratio is (0.5-1) g / mmol, for example 0.8 g / mmol.

[0062] Preferably, in the reduction reaction, the reducing agent is trichlorosilane.

[0063] Preferably, in the reduction reaction, the reducing agent and the compound 1 The equivalent ratio is (1-3):1, preferably 1.5:1.

[0064] Preferably, the reaction temperature of the reduction reaction is 70-90°C, for example 80°C.

[0065] After the filter cake is treated with the above reduction reaction, the obtained compound 2 can be further used, for example, for preparing phosphorus ylide reagents.

[0066] In one embodiment of the present invention, the method 1 or method 2 further comprises a method for preparing a solid-supported vitamin A ylide as shown in formula II, which comprises the following steps: under the action of a base, the ion as shown in formula IV undergoes a dehydrogenation reaction as shown below to prepare a solid-supported vitamin A ylide as shown in formula II, that is,

[0067]

[0068] The reaction operation and reaction conditions of the dehydrogenation reaction are conventional reaction operations and reaction conditions of this type of reaction in the art.

[0069] Preferably, in the dehydrogenation reaction, the base is an alkali metal hydroxide and / or an alkali metal carbonate, the alkali metal hydroxide is, for example, sodium hydroxide and / or potassium hydroxide, the alkali metal carbonate is, for example, sodium carbonate and / or potassium carbonate, preferably sodium carbonate.

[0070] Preferably, in the dehydrogenation reaction, the base is an alkali metal carbonate, such as sodium carbonate.

[0071] Preferably, in the dehydrogenation reaction, the base is in the form of an aqueous solution of the base, and the mass fraction of the aqueous solution of the base can be 5% to 10%, for example, 10%.

[0072] Preferably, in the dehydrogenation reaction, the base and the ion as shown in Formula IV The equivalent ratio is (1-3):1, for example (2-3):1, preferably 3:1.

[0073] Preferably, in the dehydrogenation reaction, the reaction temperature is 0-40°C, for example 10°C.

[0074] Preferably, in the dehydrogenation reaction, the reaction time is 5 to 60 min, for example, 10 min.

[0075] Preferably, in the dehydrogenation reaction, the ion represented by Formula IV is provided by a salt represented by Formula IV-1.

[0076]

[0077] in, For inorganic anions, such as Cl - 、NO3 - 、H2PO4 - or HSO4 - , preferably HSO4 - .

[0078] After the dehydrogenation reaction is completed, the post-treatment can be carried out by the following steps: filtering, washing the filter cake, and the washing solvent can be water and / or an alcohol solvent, for example, one or more selected from water, methanol and ethanol, preferably water. Based on the equivalent of, the mass of the washing solvent can be (0.5-1) g / mmol, for example 0.8 g / mmol.

[0079] In one embodiment of the present invention, the method 1 or method 2 further comprises a method for preparing an ion as shown in formula IV, which comprises the following steps: in a solvent, under the action of an inorganic acid, compound V and compound 2 undergo a substitution reaction as shown below to prepare an ion as shown in formula IV, that is,

[0080]

[0081] Wherein, the compound V is the compound V described in any of the above schemes.

[0082] The reaction operation and reaction conditions of the substitution reaction are conventional reaction operations and reaction conditions of this type of reaction in the art.

[0083] Preferably, the compound V is in the form of compound V or in the form of a crystallization mother liquor obtained after preparing compound V. In the crystallization mother liquor, the mass fraction of the compound V is preferably greater than 0% and less than 55%, for example 50%.

[0084] Preferably, the phosphorus loading in the compound 2 is 1.5 to 2 mmol / g.

[0085] Preferably, the compound 2 is the triphenylphosphine resin as described above.

[0086] Preferably, the equivalent ratio of phosphorus in the compound 2 to the compound V is (1-5):1, for example (1-2):1, preferably 1.5:1.

[0087] Preferably, in the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and halogenated alkyl solvents, the alcohol solvent may be methanol and / or ethanol (e.g. ethanol), the aromatic hydrocarbon solvent may be benzene substituted with one or more C1-C4 alkyl groups, such as toluene, and the halogenated alkyl solvent may be dichloromethane.

[0088] Preferably, in the substitution reaction, the solvent is selected from water and / or alcohol solvents, such as alcohol solvents, further such as ethanol.

[0089] Preferably, in the substitution reaction, the mass ratio of the compound V to the solvent is 1:(4-8), for example 1:(5-6).

[0090] Preferably, in the substitution reaction, the inorganic acid is selected from one or more of hydrochloric acid, sulfuric acid, phosphoric acid and nitric acid, such as sulfuric acid, and further such as sulfuric acid with a mass fraction of 98%.

[0091] Preferably, the equivalent ratio of the inorganic acid to the compound V is (1-2.3):1, preferably (1-1.5):1.

[0092] Preferably, the reaction temperature of the substitution reaction is 10-80°C, such as 10-15°C.

[0093] Preferably, the reaction time of the substitution reaction is 0.5 to 4 h, such as 1 h.

[0094] Preferably, after the substitution reaction is completed, post-treatment is performed by the following steps, which include: filtering, washing, and the washing is preferably ethanol and / or water washing, for example, washing with ethanol and water in turn.

[0095] The present invention also provides a compound as shown in formula II or an ion as shown in formula IV as described in any of the above schemes:

[0096]

[0097] The present invention also provides a method for preparing the compound shown in formula II, which is as described in the method for preparing the immobilized vitamin A ylide shown in formula II described in any of the above schemes.

[0098] The present invention also provides a method for preparing the compound shown in formula IV, which is as described in the method for preparing the ion shown in formula IV described in any of the above schemes.

[0099] In the present invention, if the configuration of the structure of the compound is not particularly described, it means that the configuration of the compound is not particularly limited. For example In the above, the double bond is not particularly limited to the E configuration, but may also be the Z configuration.

[0100] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0101] The reagents and raw materials used in the present invention are commercially available.

[0102] The positive and progressive effect of the present invention is that the preparation method of all-trans β-carotene of the present invention can achieve one or more of the following effects: high yield, high purity and short reaction time. DETAILED DESCRIPTION

[0103] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0104] The raw materials, bases, solvents, etc. used in the following examples were all purchased from commercial sources. The content of the product was detected by HPLC (liquid chromatography), and the yield was calculated by actual yield / theoretical yield×100%.

[0105] The carotene detection method in the following examples was carried out according to the corresponding liquid chromatography method in the European Pharmacopoeia version 9.0.

[0106] Liquid chromatography: Shimadzu LC-20AT (instrument model), chromatographic column SUPELCOSIL SUPLEX pKb-100 (chromatographic column model), specifications are column length 250 mm, column diameter 4.6 mm, and the stationary phase is amide alkyl silicon-based silica gel (particle size 5 μm).

[0107] The detection method of total phosphorus in the samples in the following examples: According to the detection method of GB 5009.87-2016 "National Food Safety Standard Determination of Phosphorus in Food", the phosphorus content was detected by molybdenum blue spectrophotometry.

[0108] The immobilized vitamin A phosphonate in the following examples is Immobilized vitamin A ylides

[0109] Example 1 Preparation of immobilized vitamin A phosphonate (using crystallization mother liquor)

[0110] In a 250mL three-necked flask, 40g of the remaining mother liquor of vitamin A acetate crystallization (of which the mass fraction of vitamin A acetate is 50% and the mass fraction of all-trans vitamin A acetate is 22.5%), 46g of commercially available triphenylphosphine resin with a phosphine loading of 2mmol / g (CAS: 39319-11-4), and 80g of ethanol were added. After nitrogen replacement, 6.2g of 98% sulfuric acid was added at 10°C, and stirring was continued at 10°C for 1 hour. After filtering, the resin was washed with 10g of ethanol and 10g of water to obtain 69g of immobilized vitamin A phosphine salt.

[0111] Example 2 Preparation of immobilized vitamin A ylides

[0112] The immobilized vitamin A phosphonate obtained in Example 1 was added to a 500 mL three-necked flask, and 196 g of 10% sodium carbonate solution was added at 10° C. The mixture was stirred for 10 minutes and then filtered. The filter cake was washed with 46 g of water to obtain 63 g of immobilized vitamin A ylide.

[0113] Example 3 Preparation of all-trans β-carotene (in situ generation of retinal)

[0114] 31.5 g of the immobilized vitamin A ylide obtained in Example 2 and 23 g of water were added to a 100 mL pressure-resistant glass bottle. After replacing the nitrogen, 4.2 g of 30% hydrogen peroxide was added, and the bottle was placed in a microwave reactor. After heating for 3 minutes at a power of 100 W (corresponding to the power of vitamin A acetate added of 10 W / g), the reaction bottle was placed in a 10° C. water bath and cooled to 25° C., 45 g of dichloromethane was added, the mixture was stirred evenly and filtered. After stratification, the oil phase was evaporated to dryness under reduced pressure at 25° C. to obtain 7.84 g of all-trans β-carotene, with a liquid phase content of 99.1% and a yield of 95.1%. No total phosphorus was detected in the sample.

[0115] Example 4 Preparation of all-trans β-carotene (with added retinal)

[0116] 31.5 g of the immobilized vitamin A ylide obtained in Example 2 and 46 g of methanol were added to a 200 mL pressure-resistant glass bottle, and then 8.65 g of retinal was added. After replacing the nitrogen, the mixture was placed in a microwave reactor and heated at a power of 200 W (corresponding to the power of vitamin A acetate added of 20 W / g) for 3 minutes. The reaction bottle was placed in a 10° C. water bath and cooled to room temperature. The filtrate was filtered and concentrated to dryness at below 30° C. 46 g of dichloromethane was added to wash the filter cake, and the dichloromethane phase was washed with 10 g of water. After stratification, the oil phase was evaporated to dryness under reduced pressure at 25° C. A total of 16.02 g of all-trans β-carotene was obtained, with a liquid phase content of 99.2% and a yield of 97.3%. No total phosphorus was detected in the sample.

[0117] Example 5 Preparation of immobilized vitamin A phosphonate (using vitamin A acetate powder with a content of more than 97%)

[0118] In a 250mL three-necked flask, add 20.6g of vitamin A acetate powder (of which the mass fraction of vitamin A acetate is 97.1% and the mass fraction of all-trans vitamin A is 95.9%), 46g of commercially available triphenylphosphine resin with a phosphine loading of 2mmol / g (CAS: 39319-11-4), and 120g of ethanol. After nitrogen replacement, add 6.2g of 98% sulfuric acid at 10°C, continue stirring at 10°C for 1 hour, filter, wash the resin with 10g of ethanol and 10g of water, and obtain 69.2g of immobilized vitamin A phosphine salt.

[0119] Example 6 Preparation of immobilized vitamin A ylide (vitamin A source is vitamin A acetate powder with a content of more than 97%)

[0120] The immobilized vitamin A phosphonate obtained in Example 5 was added to a 500 mL three-necked flask, and 196 g of 10% sodium carbonate solution was added at 10° C. The mixture was stirred for 10 minutes and filtered. The filter cake was washed with 46 g of water to obtain 63 g of immobilized vitamin A ylide.

[0121] Example 7 Preparation of all-trans β-carotene (vitamin A source is vitamin A acetate powder with a content of more than 97%)

[0122] The operation was the same as that in Example 3, and finally 7.89 g of all-trans β-carotene was obtained, with a liquid phase content of 99.0% and a yield of 95.6%.

[0123] Example 10 Resurrection of triphenylphosphine resin

[0124] The resins obtained in Example 3 and Example 4 were combined, washed with 40 g of ethanol, and dried in vacuo at 30°C. Then, 46 g of n-heptane was added. After nitrogen substitution, 12.5 g of trichlorosilane was added. After stirring at 80°C for 3 hours, the mixture was filtered to obtain 46 g of revived triphenylphosphine resin.

[0125] Example 11 Preparation of all-trans-β-carotene using revived triphenylphosphine resin

[0126] The operation method is the same as that of Example 1, Example 2 and Example 3, except that when preparing the immobilized vitamin A phosphonate, the resin used is the one prepared in Example 10, and 7.87 g of all-trans β-carotene is obtained, the liquid phase content of all-trans β-carotene is 99.1%, the yield is 95.5%, and no total phosphorus is detected in the sample.

[0127] Comparative Example 1 The steps for preparing immobilized vitamin A ylide are the same as those in Example 1 and Example 2

[0128] The difference between the preparation of all-trans β-carotene and Example 3 is that when preparing all-trans β-carotene by condensation, microwave heating is not used, but oil bath heating is used.

[0129] 31.5 g of immobilized vitamin A ylide and 23 g of water were added to a 100 mL three-necked flask. After replacing the nitrogen, 4.2 g of 30% hydrogen peroxide was added, and the flask was placed in an oil bath. The reaction temperature was set to 10°C. After reacting for 3 hours, the heating temperature was increased to 100°C, and stirring was continued for 3 hours. The flask was then cooled to 25°C, 45 g of dichloromethane was added, and the mixture was stirred evenly and filtered. After stratification, the oil phase was evaporated to dryness under reduced pressure at 25°C to obtain 4.33 g of oily β-carotene with a liquid content of 97%, of which all-trans β-carotene accounted for 82%, with a yield of 51.4%, and no total phosphorus was detected in the sample.

[0130] Comparative Example 2: Preparation of β-carotene by microwave reaction without using immobilized triphenylphosphine but directly using triphenylphosphine

[0131] In a 250mL three-necked flask, add 40g of the remaining mother liquor of vitamin A acetate crystallization (containing 50% by mass of total vitamin A, including 22.5% by mass of all-trans vitamin A acetate), 16g of triphenylphosphine, and 80g of methanol. After nitrogen replacement, add 6.1g of 98% sulfuric acid at 10°C and stir at 10°C for 16 hours, then add 20g of water and 20g of heptane. After separating the heptane phase, distill off 100g of methanol from the methanol-water phase at below 40°C, and add 100g of water. At 10°C, 300 g of 10% sodium bicarbonate and 10 g of 30% hydrogen peroxide were added, placed in a microwave reactor, reacted at normal pressure, heated at a power of 100 W for 3 minutes, and then the reaction bottle was placed in a 10°C water bath and cooled to 25°C, and then 60 g of dichloromethane was added, stirred evenly and filtered. After stratification, the oil phase was evaporated to dryness under reduced pressure at 25°C, and then heated to reflux with 80 g of ethanol, cooled to 10°C, filtered, and vacuum dried to obtain 8.85 g of solid, with a liquid phase content of all-trans β-carotene of 96.1% and a yield of 52.9%. In the solid, the content of triphenylphosphine was 0.03%, and the content of triphenylphosphine oxide was 0.06%.

[0132] Comparative Example 3 Preparation of all-trans β-carotene (microwave reaction time is not within the preferred range)

[0133] The operation method is similar to that of Example 1, Example 2 and Example 3, except that, when preparing all-trans β-carotene, the microwave reaction time is 15 minutes. Finally, the dichloromethane solution is evaporated to dryness to obtain 8.17 g of crude β-carotene. The crude product is heated to reflux with 40 g of ethanol and then cooled to 10° C. and filtered. The liquid content of 4.45 g of all-trans β-carotene is 95.3%, and the yield is 51.9%.

[0134] Comparative Example 4 Preparation of all-trans β-carotene (microwave power is not within the preferred range)

[0135] The operation method is similar to that of Example 1, Example 2 and Example 3, except that, when preparing all-trans β-carotene, the power of the microwave reactor is set to 20 W according to the feed ratio of Example 3, and the power of the added vitamin A acetate is 2 W / g. After the dichloromethane solution is evaporated to dryness, 7.75 g of crude β-carotene is obtained. The crude product is heated to reflux with 40 g of ethanol, cooled to 10° C. and filtered, and 6.29 g of all-trans β-carotene is obtained, the liquid content is 98.3%, and the yield is 75.6%.

Claims

1. A method for preparing all-trans β-carotene, which is the following method 1 or method 2: Method 1: It comprises the following steps: In a solvent, under the action of microwaves, the compound shown in formula I and the immobilized vitamin A ylide shown in formula II undergo Wittig reaction as shown below to prepare all-trans β-carotene shown in formula III, that is, In the Wittig reaction, the immobilized vitamin A ylide as shown in formula II is The Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. The equivalent of is taken as the reference, and the setting power of the microwave reactor is 5-10W / mmol; Alternatively, the Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent vitamin A derivative, the set power of the microwave reactor is 15-30 W / g; the vitamin A derivative is compound V as shown below: R is acetyl; Method 2: It comprises the following steps: in a solvent, under the action of an oxidant and microwaves, the immobilized vitamin A ylide shown in formula II undergoes an oxidative coupling reaction as shown below to prepare all-trans β-carotene shown in formula III, that is, In the oxidative coupling reaction, the immobilized vitamin A ylide as shown in formula II is The oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. The equivalent of is taken as the reference, and the setting power of the microwave reactor is 2.7-5 W / mmol; Alternatively, the oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent vitamin A derivative, the set power of the microwave reactor is 8-15 W / g; the vitamin A derivative is compound V as shown below: R is acetyl; in, In the immobilized vitamin A ylide as shown in formula II, the Triphenylphosphine resin In The CAS number of the triphenylphosphine resin is 39319-11-4; Wherein, the reaction time of the Wittig reaction or the oxidative coupling reaction is 1 to 10 minutes.

2. The method for preparing all-trans β-carotene according to claim 1, characterized in that: It meets one or more of the following conditions: (1) The Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. The equivalent of is taken as the reference, and the setting power of the microwave reactor is 6-8.3W / mmol; (2) The oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. The equivalent of is taken as the benchmark, and the set power of the microwave reactor is 3.3W / mmol; (3) In the Wittig reaction or the oxidative coupling reaction, the frequency of the microwave is 2000-3000 MHz; (4) The reaction time of the Wittig reaction or the oxidative coupling reaction is 2 to 5 minutes; (5) In the Wittig reaction, the solvent is water and / or an alcohol solvent; (6) In the Wittig reaction, the mass ratio of the solvent to the compound represented by formula I is (3-8):1; (7) In the Wittig reaction, the compound of formula I and the immobilized vitamin A ylide of formula II The equivalent ratio is (1-1.2):1; (8) In the oxidative coupling reaction, the solvent is water and / or an alcohol solvent; (9) In the oxidative coupling reaction, the solvent and the immobilized vitamin A ylide of formula II The mass equivalent ratio is 0.5~1.5g / mmol; (10) In the oxidative coupling reaction, the oxidant is hydrogen peroxide; (11) In the oxidative coupling reaction, the oxidant and the immobilized vitamin A ylide of formula II The equivalent ratio is (0.3-1.5):1; (12) The Wittig reaction or the oxidative coupling reaction is carried out in an inert gas; (13) After the Wittig reaction is completed, post-treatment is performed by the following steps, which include: filtering and concentrating; (14) After the oxidative coupling reaction is completed, post-treatment is performed by the following steps, which include: mixing with a water-insoluble organic solvent, filtering, and concentrating the organic phase in the filtrate.

3. The method for preparing all-trans β-carotene according to claim 2, characterized in that: It meets one or more of the following conditions: (1) In the Wittig reaction or the oxidative coupling reaction, the frequency of the microwave is 2450 MHz; (2) In the Wittig reaction, the solvent is an alcohol solvent; (3) In the Wittig reaction, the mass ratio of the solvent to the compound represented by Formula I is 5.3:1; (4) In the Wittig reaction, the compound of formula I and the immobilized vitamin A ylide of formula II The equivalent ratio is 1:1 or 1.1:1; (5) In the oxidative coupling reaction, the solvent is water; (6) In the oxidative coupling reaction, the solvent and the immobilized vitamin A ylide of formula II The mass equivalent ratio is 0.8g / mmol; (7) In the oxidative coupling reaction, the oxidant is hydrogen peroxide with a mass fraction of 10% to 50%; (8) In the oxidative coupling reaction, the oxidant and the immobilized vitamin A ylide of formula II The equivalent ratio is (0.8-1.3):1; (9) The Wittig reaction or the oxidative coupling reaction is carried out in an inert gas, wherein the inert gas is nitrogen; (10) The Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. The equivalent of is taken as the benchmark, and the set power of the microwave reactor is 6.7W / mmol; (11) The reaction time of the Wittig reaction or the oxidative coupling reaction is 3 min.

4. The method for preparing all-trans β-carotene according to claim 2, characterized in that: It meets one or more of the following conditions: (1) In the Wittig reaction, the solvent is water and / or an alcohol solvent, and the alcohol solvent is methanol and / or ethanol; (2) In the oxidative coupling reaction, the solvent is water and / or an alcohol solvent, and the alcohol solvent is methanol and / or ethanol; (3) In the oxidative coupling reaction, the oxidant is hydrogen peroxide with a mass fraction of 30%; (4) In the oxidative coupling reaction, the oxidant and the immobilized vitamin A ylide of formula II The equivalent ratio is (1~1.3):

1.

5. The method for preparing all-trans β-carotene according to claim 4, characterized in that: It meets one or more of the following conditions: (1) In the Wittig reaction, the solvent is water and / or an alcohol solvent, and the alcohol solvent is methanol; (2) In the oxidative coupling reaction, the solvent is water and / or an alcohol solvent, and the alcohol solvent is methanol; (3) In the oxidative coupling reaction, the oxidant and the immobilized vitamin A ylide of formula II The equivalent ratio is 1.3:

1.

6. The method for preparing all-trans β-carotene according to claim 1, characterized in that: It meets one or more of the following conditions: (1) After the Wittig reaction is completed, post-treatment is performed by the following steps, which include: filtering and concentrating; after the oxidative coupling reaction is completed, post-treatment is performed by the following steps, which include: mixing with a water-insoluble organic solvent, filtering, and concentrating the organic phase in the filtrate; in the post-treatment steps of the Wittig reaction and the oxidative coupling reaction, the temperature during the concentration is 25 to 35°C; (2) After the Wittig reaction is completed, post-treatment is performed by the following steps, which include: filtering and concentrating; after the oxidative coupling reaction is completed, post-treatment is performed by the following steps, which include: mixing with a water-insoluble organic solvent, filtering, and concentrating the organic phase in the filtrate; in the post-treatment step of the Wittig reaction or the oxidative coupling reaction, after the filtration, a filter cake is retained, and the filter cake includes The filter cake is recorded as compound 1, and the filter cake is post-treated by the following steps, which include: in the presence of an organic solvent or in the absence of a solvent, under the action of a reducing agent, the filter cake is subjected to the following reduction reaction to prepare compound 2, that is, 7. The method for preparing all-trans β-carotene according to claim 6, characterized in that: After the Wittig reaction is completed, post-treatment is performed by the following steps, which include: filtering and concentrating; after the oxidative coupling reaction is completed, post-treatment is performed by the following steps, which include: mixing with a water-insoluble organic solvent, filtering, and concentrating the organic phase in the filtrate; in the post-treatment steps of the Wittig reaction and the oxidative coupling reaction, the temperature during the concentration is 30°C.

8. The method for preparing all-trans β-carotene according to claim 1, characterized in that: It meets one or more of the following conditions: (1) The Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. Based on the mass of the same equivalent vitamin A derivative, the set power of the microwave reactor is 18-25 W / g; the vitamin A derivative is compound V as shown below: R is acetyl; (2) The oxidative coupling reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide as shown in formula II. Based on the mass of the same equivalent vitamin A derivative, the set power of the microwave reactor is 10W / g; the vitamin A derivative is compound V as shown below: R is acetyl.

9. The method for preparing all-trans β-carotene according to claim 1, characterized in that: The Wittig reaction is carried out in a microwave reactor to react with the immobilized vitamin A ylide shown in formula II. The mass of the same equivalent vitamin A derivative is used as a reference, the set power of the microwave reactor is 20W / g, and the vitamin A derivative is compound V as shown below: R is acetyl.

10. The method for preparing all-trans β-carotene according to claim 6, characterized in that: It meets one or more of the following conditions: (1) The reduction reaction is carried out in the presence of an organic solvent; (2) In the reduction reaction, the organic solvent is selected from one or more of a halogenated alkane solvent, a hydrocarbon solvent and an alcohol solvent; (3) When the reduction reaction is carried out in the presence of an organic solvent, the organic solvent and the compound 1 The mass molar ratio is (0.5~1) g / mmol; (4) In the reduction reaction, the reducing agent is trichlorosilane; (5) In the reduction reaction, the reducing agent and the compound 1 The equivalent ratio is (1-3):1; (6) The reaction temperature of the reduction reaction is 70 to 90°C.

11. The method for preparing all-trans β-carotene according to claim 10, characterized in that: It meets one or more of the following conditions: (1) In the reduction reaction, the organic solvent is a hydrocarbon solvent; (2) When the reduction reaction is carried out in the presence of an organic solvent, the organic solvent and the compound 1 The mass molar ratio is 0.8g / mmol; (3) In the reduction reaction, the reducing agent and the compound 1 The equivalent ratio is 1.5:1; (4) The reaction temperature of the reduction reaction is 80°C.

12. The method for preparing all-trans β-carotene according to claim 10, characterized in that: The hydrocarbon solvent is a benzene solvent or a cyclic hydrocarbon solvent.

13. The method for preparing all-trans β-carotene according to claim 10, characterized in that: In the reduction reaction, the organic solvent is selected from one or more of a halogenated alkane solvent, a hydrocarbon solvent and an alcohol solvent, and the halogenated alkane solvent is dichloromethane.

14. The method for preparing all-trans β-carotene according to claim 10, characterized in that: In the reduction reaction, the organic solvent is selected from one or more of a halogenated alkane solvent, a hydrocarbon solvent and an alcohol solvent, and the hydrocarbon solvent is n-heptane or n-hexane.

15. The method for preparing all-trans β-carotene according to claim 10, characterized in that: In the reduction reaction, the organic solvent is selected from one or more of a halogenated alkane solvent, a hydrocarbon solvent and an alcohol solvent, and the alcohol solvent is ethanol.

16. The method for preparing all-trans β-carotene according to claim 12, characterized in that: The benzene solvent is toluene.

17. The method for preparing all-trans β-carotene according to claim 12, characterized in that: The cyclic hydrocarbon solvent is cyclohexane.

18. The method for preparing all-trans β-carotene according to claim 10, characterized in that: In the reduction reaction, the organic solvent is selected from one or more of a halogenated alkane solvent, a hydrocarbon solvent and an alcohol solvent, and the hydrocarbon solvent is n-heptane.

19. The method for preparing all-trans β-carotene according to claim 1, characterized in that: The method 1 or method 2 further comprises a method for preparing the immobilized vitamin A ylide as shown in formula II, which comprises the following steps: under the action of a base, the ion as shown in formula IV undergoes a dehydrogenation reaction as shown below to prepare the immobilized vitamin A ylide as shown in formula II, that is, 20. The method for preparing all-trans β-carotene according to claim 19, characterized in that: It meets one or more of the following conditions: (1) In the dehydrogenation reaction, the base is an alkali metal hydroxide and / or an alkali metal carbonate; (2) In the dehydrogenation reaction, the base and the ion shown in formula IV The equivalent ratio is (1-3):1; (3) The reaction temperature of the dehydrogenation reaction is 0 to 40°C; (4) The reaction time of the dehydrogenation reaction is 5 to 60 minutes; (5) In the dehydrogenation reaction, the ion represented by Formula IV is provided by the salt represented by Formula IV-1, in, It is an inorganic anion.

21. The method for preparing all-trans β-carotene according to claim 20, characterized in that: It meets one or more of the following conditions: (1) In the dehydrogenation reaction, the base is an alkali metal carbonate; (2) In the dehydrogenation reaction, the base and the ion shown in formula IV The equivalent ratio is (2-3):1; (3) The reaction temperature of the dehydrogenation reaction is 10°C; (4) The reaction time of the dehydrogenation reaction is 10 min; (5) In the dehydrogenation reaction, the ion represented by Formula IV is provided by the salt represented by Formula IV-1, in, Cl - 、NO3 - 、H2PO4 - or HSO4 - .

22. The method for preparing all-trans β-carotene according to claim 21, characterized in that: It meets one or more of the following conditions: (1) In the dehydrogenation reaction, the base and the ion shown in formula IV The equivalent ratio is 3:1; (2) In the dehydrogenation reaction, the ion represented by Formula IV is provided by the salt represented by Formula IV-1, in, HSO4 - .

23. The method for preparing all-trans β-carotene according to claim 20, characterized in that: In the dehydrogenation reaction, the base is an alkali metal hydroxide and / or an alkali metal carbonate, and the alkali metal hydroxide is sodium hydroxide and / or potassium hydroxide.

24. The method for preparing all-trans β-carotene according to claim 20, characterized in that: In the dehydrogenation reaction, the base is an alkali metal hydroxide and / or an alkali metal carbonate, and the alkali metal carbonate is sodium carbonate and / or potassium carbonate.

25. The method for preparing all-trans β-carotene according to claim 20, characterized in that: In the dehydrogenation reaction, the base is an alkali metal hydroxide and / or an alkali metal carbonate, and the alkali metal carbonate is sodium carbonate.

26. The method for preparing all-trans β-carotene according to claim 19, characterized in that: The method 1 or method 2 further comprises a method for preparing an ion as shown in formula IV, which comprises the following steps: in a solvent, under the action of an inorganic acid, compound V and compound 2 undergo a substitution reaction as shown below to prepare an ion as shown in formula IV, that is, Wherein, the compound V is R is hydrogen, -C(=O)-(C1-C6 alkyl) or palmitoyl.

27. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the R, the "C1-C6 alkyl" is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

28. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the R, the "C1-C6 alkyl" is a methyl group or an ethyl group.

29. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the R, the "C1-C6 alkyl" is a methyl group.

30. The method for preparing all-trans β-carotene according to claim 26, characterized in that: The R is hydrogen, acetyl, propionyl or palmitoyl.

31. The method for preparing all-trans β-carotene according to claim 26, characterized in that: The R is an acetyl group.

32. The method for preparing all-trans β-carotene according to any one of claims 26 to 31, characterized in that: It meets one or more of the following conditions: (1) In the substitution reaction, the compound V is in the form of a crystallization mother solution obtained after preparing the compound V; (2) In the substitution reaction, the phosphorus loading in the compound 2 is 1.5-2 mmol / g; (3) In the substitution reaction, the compound 2 is the triphenylphosphine resin as described in claim 1; (4) In the substitution reaction, the equivalent ratio of phosphorus in the compound 2 to the compound V is (1-5):1; (5) In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and alkyl halide solvents; (6) In the substitution reaction, the mass ratio of the compound V to the solvent is 1:(4-8); (7) In the substitution reaction, the inorganic acid is selected from one or more of hydrochloric acid, sulfuric acid, phosphoric acid and nitric acid; (8) In the substitution reaction, the equivalent ratio of the inorganic acid to the compound V is (1-2.3):1; (9) The reaction temperature of the substitution reaction is 10 to 80°C; (10) The reaction time of the substitution reaction is 0.5 to 4 hours.

33. The method for preparing all-trans β-carotene according to claim 32, characterized in that: It meets one or more of the following conditions: (1) In the substitution reaction, the compound V is in the form of a crystallization mother liquor obtained after preparing the compound V, and the mass fraction of the compound V in the crystallization mother liquor is greater than 0% and less than 55%; (2) In the substitution reaction, the equivalent ratio of phosphorus in the compound 2 to the compound V is (1-2):1; (3) In the substitution reaction, the solvent is an alcohol solvent and / or water; (4) In the substitution reaction, the mass ratio of the compound V to the solvent is 1:(5-6); (5) In the substitution reaction, the inorganic acid is sulfuric acid; (6) In the substitution reaction, the equivalent ratio of the inorganic acid to the compound V is (1-1.5):1; (7) The reaction temperature of the substitution reaction is 10 to 15°C; (8) The reaction time of the substitution reaction is 1 h.

34. The method for preparing all-trans β-carotene according to claim 33, characterized in that: It meets one or more of the following conditions: (1) In the substitution reaction, the compound V is in the form of a crystallization mother liquor obtained after preparing the compound V, and the mass fraction of the compound V in the crystallization mother liquor is 50%; (2) In the substitution reaction, the equivalent ratio of phosphorus in the compound 2 to the compound V is 1.5:1; (3) In the substitution reaction, the solvent is an alcohol solvent; (4) In the substitution reaction, the inorganic acid is sulfuric acid with a mass fraction of 98%.

35. The method for preparing all-trans β-carotene according to claim 26, characterized in that In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and halogenated alkyl solvents, and the alcohol solvent is methanol and / or ethanol.

36. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and halogenated alkyl solvents, and the aromatic hydrocarbon solvent is benzene substituted with one or more C1-C4 alkyl groups.

37. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and alkyl halide solvents, and the alkyl halide solvent is dichloromethane.

38. The method for preparing all-trans β-carotene according to claim 26, characterized in that In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and halogenated alkyl solvents, and the alcohol solvent is ethanol.

39. The method for preparing all-trans β-carotene according to claim 26, characterized in that: In the substitution reaction, the solvent is selected from one or more of water, alcohol solvents, aromatic hydrocarbon solvents and halogenated alkyl solvents, and the aromatic hydrocarbon solvent is toluene.

40. The compound represented by formula II or the ion represented by formula IV, in, The compound represented by formula II is the compound represented by formula II as described in any one of claims 1 to 9; the ion represented by formula IV is the ion represented by formula IV as described in any one of claims 19 to 22.

41. A method for preparing the compound of formula II or the ion of formula IV as claimed in claim 40, characterized in that: The preparation method of the compound of formula II is as described in the preparation method of the immobilized vitamin A ylide of formula II as described in any one of claims 19 to 25; The method for preparing the ion represented by formula IV is as described in the method for preparing the ion represented by formula IV as described in any one of claims 26-39.

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