A method for preparing vitamin A

Abstract

The invention provides a method for preparing vitamin A, wherein pentadecanphosphonate or pentadecanphosphonate reacts with 2-methyl-4-acetoxy-2-butenal and alkali to prepare vitamin A, wherein the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.02% to 0.8%. The invention improves the content of all-trans vitamin A in the obtained vitamin A crude product by controlling the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal.

Description

Technical Field

[0001] The invention belongs to the field of fine chemical synthesis, and in particular relates to a method for preparing vitamin A. Background Art

[0002] Vitamin A is an important nutritional chemical that promotes human growth and development and can enhance resistance to disease. Vitamin A is also an important feed additive, which has many physiological functions such as promoting the synthesis of immunoglobulins in animals, promoting growth and reproduction. Among them, all-trans vitamin A has the highest physiological activity.

[0003] The crude vitamin A obtained by chemical synthesis contains many vitamin A isomers. The content of all-trans vitamin A is usually only 60% to 70%. It must be purified by crystallization to obtain high-purity all-trans vitamin A. Vitamin A isomers solubilize vitamin A, reducing the crystallization yield. The single crystallization yield is no more than 80%. A large amount of vitamin A and its isomers remain in the crystallization mother liquor, resulting in product loss.

[0004] In order to overcome the defects in the existing production process, it is necessary to find a preparation method for producing high all-trans vitamin A content. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing vitamin A, which improves the selectivity of the all-trans structure of vitamin A by controlling the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in the raw material 2-methyl-4-acetoxy-2-butenal.

[0006] In order to achieve the above invention object, the present invention adopts the following technical solution:

[0007] A method for preparing vitamin A comprises reacting pentadecylphosphonate or pentadecylphosphonate with 2-methyl-4-acetoxy-2-butenal and alkali to prepare vitamin A, wherein the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.02% to 0.8%, preferably 0.1% to 0.5%.

[0008] The structure of 2-methyl-4-acetoxy-2-butenal is

[0009] The structure of 2-methyl-3,4-diacetoxybutyraldehyde is

[0010] The structure of 2-methyl-3-acetoxy-3-butene-1-aldehyde is

[0011] In the present invention, 2-methyl-4-acetoxy-2-butenal is synthesized by the following method: (a) 3,4-diacetyl-1-butene undergoes a hydroformylation reaction under the action of a rhodium catalyst to generate 2-methyl-3,4-diacetoxybutyraldehyde; (b) 2-methyl-3,4-diacetoxybutyraldehyde reacts under the action of acetic acid and sodium acetate to generate 2-methyl-4-acetoxy-2-butenal.

[0012] Among them, the preferred rhodium catalyst for the hydroformylation reaction in step (a) is acetylacetonato carbonyl rhodium, and the amount of the rhodium catalyst used is 0.01% to 0.1% of the molar amount of 3,4-diacetoxy-1-butene calculated as rhodium atom; the reaction pressure is 2 to 4 MPa, the reaction temperature is 60 to 100° C., and the reaction time is 2 to 4 hours; in the reaction in step (b), the amount of acetic acid used is 1% to 5% of the molar amount of 2-methyl-3,4-diacetoxybutyraldehyde, the amount of sodium acetate used is 1% to 5% of the molar amount of 2-methyl-3,4-diacetoxybutyraldehyde, the molar ratio of acetic acid to sodium acetate is 0.5:1 to 2:1, the reaction temperature is 100 to 120° C., and the reaction time is 2 to 4 hours.

[0013] During the reaction in step (b), the content of 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is controlled by regulating the ratio of acetic acid to sodium acetate; and the content of 2-methyl-3,4-diacetoxybutyraldehyde in 2-methyl-4-acetoxy-2-butenal is controlled by regulating the reaction temperature and reaction time.

[0014] The mechanism of preparing vitamin A by the reaction of pentadecanphosphine salt with 2-methyl-4-acetoxy-2-butenal and base is as follows:

[0015]

[0016] The mechanism of the reaction of pentadecanedaphosphonate with 2-methyl-4-acetoxy-2-butenal and base to prepare vitamin A is as follows:

[0017]

[0018] Among them, reaction (1) is the reaction of pentadecanphosphonate or pentadecanphosphonate with base to form ylide; (2) ylide and 2-methyl-4-acetoxy-2-butenal undergo 2+2 reaction to form a four-membered ring intermediate; (3) the four-membered ring intermediate undergoes reverse 2+2 reaction to form VA and VA isomers.

[0019] In the process of the reverse 2+2 reaction in step (3), a C=C double bond is formed to generate all-trans VA and cis isomers. In this process, 2-methyl-3,4-diacetoxybutyraldehyde or 2-methyl-3-acetoxy-3-butene-1-aldehyde uses two C=Os in close spatial positions to interact remotely with the four-membered ring intermediate, thereby improving the selectivity of all-trans VA; at the same time, the aldehyde group of 2-methyl-3,4-diacetoxybutyraldehyde or 2-methyl-3-acetoxy-3-butene-1-aldehyde will also react with ylide in a 2+2 reaction and a subsequent reverse 2+2 reaction to generate non-VA substances. Therefore, the total amount of 2-methyl-3,4-diacetoxybutyraldehyde or 2-methyl-3-acetoxy-3-butene-1-aldehyde needs to be controlled within a certain range, which not only increases the content of the all-trans structure, but also avoids the production of more by-products, thereby improving the overall selectivity and yield.

[0020] In the present invention, the pentadecanedione phosphonate is R is an alkyl group with 1 to 6 carbon atoms, preferably ethyl pentadecanoate

[0021] In the present invention, the pentadecanphosphine salt is a hydrochloride Hydrobromide Acetate Dihydrogen phosphate Bisulfate One or more of .

[0022] In the present invention, the molar ratio of the pentadecylphosphonate or phosphonium salt to 2-methyl-4-acetoxy-2-butenal is 1:1 to 1:1.1.

[0023] In the present invention, the base is one or more of alkali metal hydrides, alkali metal amides, alkali metal alkylates, alkali metal hydroxides, alkali metal alkoxides, and alkali metal carbonates; preferably one or more of sodium hydroxide, sodium methoxide, and sodium carbonate.

[0024] In the present invention, the molar ratio of the base to the pentadecylphosphonate or phosphonium salt is 1.1:1 to 1.3:1.

[0025] In the present invention, the reaction temperature is 30 to 60°C.

[0026] In the present invention, the solvent is one or more of water, methanol, tetrahydrofuran, dioxane, dimethoxyethane, and N,N-dimethylformamide.

[0027] In the present invention, the amount of solvent used is 2 to 3 times the mass of the pentadecylphosphonate or phosphonium salt.

[0028] In the present invention, the reaction time is 0.5 to 2 hours.

[0029] In the present invention, after the reaction is completed, one of hexane, heptane or petroleum ether (boiling range 60-90° C.) is used for extraction, and the extract is washed with water and then the solvent is removed to obtain a crude vitamin A product; the crude vitamin A product is crystallized using methanol or ethanol to obtain a vitamin A product.

[0030] Compared with the existing technology, the method of the present invention has the following positive effects:

[0031] 1. The content of all-trans vitamin A in crude vitamin A is higher than 85%;

[0032] 2. The single crystallization yield of vitamin A is higher than 90%. DETAILED DESCRIPTION

[0033] The method of the present invention is further described below by means of specific examples, but the present invention is not limited to the examples listed, and should also include any other known changes within the scope of the claims of the present invention.

[0034] Specifications and sources of main reagents

[0035] Reagent name Reagent Specifications Manufacturer Pentadecylphosphonate ≥99.5％ WuXi AppTec Pentadecylphosphine salt ≥98％ Rentai Biotechnology 3,4-Diacetoxy-1-butene ≥95％ Sigma Sodium methoxide solution 5mol / L methanol solution Braingway Sodium hydroxide ≥97％ Braingway Sodium carbonate ≥99.5％ Braingway

[0036] Gas chromatography analysis (GC): model Agilent WAX:1701.42249; carrier gas is high-purity nitrogen; injection mode is automatic injector; nitrogen flow rate is 64.5ml / min; vaporization chamber temperature is 280℃; split injection, split ratio is 1:40; injection volume is 0.2μl; column flow rate is 1.5ml / min; column temperature is first-order programmed temperature increase, initial temperature is 100℃, maintained for 2 minutes, then increased to 230℃ at a rate of 15℃ / min, maintained for 15 minutes; total running time is 25.67min; detector temperature is 300℃; external standard method is used for quantification, for quantitative analysis of 2-methyl-4-acetoxy-2-butenal.

[0037] High performance liquid analysis (HPLC): Shimadzu LC-20A, equipped with SIL-20A autosampler, CTO-10ASvp column oven, SPD-M20A detector, or instruments with equivalent performance. Liquid chromatography conditions: injection volume 1μL, UV detection wavelength 328nm, column oven: 40℃, flow rate: 0.4ml / min. The external standard method was used for quantitative and qualitative analysis of vitamin A.

[0038] NMR analysis: Bruker Fourier 300, used for qualitative analysis.

[0039] Example 1

[0040] Add acetylacetonato carbonyl rhodium (0.2mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat it to 100℃, charge it with synthesis gas to a pressure of 4MPaG, and maintain the reaction pressure and temperature for 4 hours. After the reaction is over, reduce the temperature to room temperature and release the pressure. Perform vacuum distillation at 100PaA, add acetic acid (0.02mol) and sodium acetate (0.04mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat it to 100℃, and react for 2 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.78%.

[0041] 2-methyl-4-acetoxy-2-butenal containing 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-buten-1-al was separated by column chromatography to obtain pure products of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-buten-1-al (purity ≥ 98%), respectively. After the structures were confirmed by nuclear magnetic resonance, they were used as standards for GC quantitative analysis.

[0042] 2-Methyl-3,4-diacetoxybutyraldehyde 1 H NMR (300MHz, CDCl3): δ=9.68(d,J H-H =4.8Hz,1H),4.73(m,1H),4.38(m,2H),3.15(m,1H),2.28(s,3H),2.27(s,3H),1.18(d,J H-H =4.5Hz,3H).

[0043] 2-Methyl-3-acetoxy-3-butene-1-aldehyde 1 H NMR (300MHz, CDCl3): δ=9.74(d,J H-H =4.8Hz,1H),4.85(d,J H-H =6.6Hz,1H),4.41(d,J H-H =6.6Hz,1H),3.25(m,1H),2.05(s,3H),0.98(d, 2 J H-H =4.5Hz,3H).

[0044] 342g 1,3-bis-double bond pentadecanoic acid ester (1.00mol) and 144g 2-methyl-4-acetoxy-2-butenal were dissolved in 685g methanol and heated to 30°C. 220mL sodium methoxide solution (5mol / L) was added dropwise thereto, and the dropping speed was controlled so that the reaction temperature did not exceed 20°C. After the addition was completed, the temperature was maintained at 30°C and the reaction was continued for 2h. After the reaction was completed, 1L of n-hexane was added to the reaction solution for extraction. After the hexane extract was washed with 0.5L of water, the solvent was removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers was 95.5%, and the mass content of all-trans vitamin A was 89.5%. 0.5L of methanol was added thereto, and the methanol solution was gradually cooled to -20°C for crystallization, filtered and dried to obtain 290g of VA crystals with a purity of ≥98%.

[0045] Example 2

[0046] Add acetylacetone carbonyl rhodium (2mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat to 60°C, charge with synthesis gas to a pressure of 2MPaG, maintain the reaction pressure and temperature for 3 hours. After the reaction is over, reduce to room temperature and release the pressure. Distill under reduced pressure at 100PaA, add acetic acid (0.06mol) and sodium acetate (0.06mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat to 120°C, and react for 3 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.49%.

[0047] 342g 2,4-di-double bond pentadecanoic acid ester (1.00mol) and 151g 2-methyl-4-acetoxy-2-butenal were dissolved in 1000g DMF and heated to 30°C. 240mL sodium methoxide solution (5mol / L) was added dropwise thereto, and the dropping speed was controlled so that the reaction temperature did not exceed 30°C. After the addition was completed, the temperature was maintained at 30°C and the reaction was continued for 1h. After the reaction was completed, 1L of n-hexane was added to the reaction solution for extraction. After the hexane extract was washed with 0.5L of water, the solvent was removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers was 96.8%, and the mass content of all-trans vitamin A was 91.3%. 0.5L of ethanol was added thereto, and the ethanol solution was gradually cooled to -20°C for crystallization, filtered and dried to obtain 300g of VA crystals with a purity of ≥98%.

[0048] Example 3

[0049] Add acetylacetone carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat to 80℃, charge with synthesis gas to a pressure of 4MPaG, maintain the reaction pressure and temperature for 4 hours. After the reaction is over, reduce to room temperature and release the pressure. Distill under reduced pressure at 100PaA, add acetic acid (0.1mol) and sodium acetate (0.05mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat to 120℃, and react for 4 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.023%.

[0050] 504g of 15-carbon phosphine hydrochloride (1.00mol) and 148g of 2-methyl-4-acetoxy-2-butenal are dissolved in 1000g of water and heated to 60°C. 480g of sodium hydroxide aqueous solution (10wt%) is added dropwise thereto, and the dropping speed is controlled so that the reaction temperature does not exceed 60°C. After the dropwise addition is completed, 60°C is maintained and the reaction is continued for 0.5h. After the reaction is completed, 2L of n-heptane is added to the reaction solution for extraction. After the extract is washed with 1L of water, the solvent is removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers is 97.2%, and the mass content of all-trans vitamin A is 88.8%. 1L of ethanol is added thereto, and the ethanol solution is gradually cooled to -20°C for crystallization, filtered and dried to obtain VA crystals 295g with a purity of ≥98%.

[0051] Example 4

[0052] Add acetylacetone carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat to 100℃, charge with synthesis gas to a pressure of 4MPaG, maintain the reaction pressure and temperature for 3 hours. After the reaction is completed, reduce to room temperature and release the pressure. Perform vacuum distillation at 100PaA, add acetic acid (0.08mol) and sodium acetate (0.04mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat to 120℃, and react for 3 hours. After the reaction is completed, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.11%.

[0053] 546g of 15-carbon phosphine hydrobromide (1.00mol) and 148g of 2-methyl-4-acetoxy-2-butenal were dissolved in 1000g of water and heated to 40°C. 680g of sodium carbonate aqueous solution (1.2mol) was added dropwise thereto, and the dropping speed was controlled so that the reaction temperature did not exceed 40°C. After the addition was completed, 40°C was maintained and the reaction was continued for 2h. After the reaction was completed, 2L of n-heptane was added to the reaction solution for extraction. After the extract was washed with 1L of water, the solvent was removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers was 96.2%, and the mass content of all-trans vitamin A was 90.9%. 1L of methanol was added thereto, and the methanol solution was gradually cooled to -20°C for crystallization, filtered and dried to obtain 298.5g of VA crystals with a purity of ≥98%.

[0054] Example 5

[0055] Add acetylacetonato carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat to 80°C, charge with synthesis gas to a pressure of 4MPaG, maintain the reaction pressure and temperature for 4 hours. After the reaction is over, reduce to room temperature and release the pressure. Distill under reduced pressure at 100PaA, add acetic acid (0.04mol) and sodium acetate (0.02mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat to 110°C, and react for 3 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.66%.

[0056] 525g of 15-carbon phosphine acetate (1.00mol) and 152g of 2-methyl-4-acetoxy-2-butenal were dissolved in 1000g of methanol and heated to 50°C. 560g of sodium hydroxide aqueous solution (1.3mol) was added dropwise thereto, and the dropping speed was controlled so that the reaction temperature did not exceed 50°C. After the addition was completed, 50°C was maintained and the reaction was continued for 1h. After the reaction was completed, 2L of petroleum ether was added to the reaction solution for extraction. After the extract was washed with 1L of water, the solvent was removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers was 96%, and the mass content of all-trans vitamin A was 90.3%. 1L of ethanol was added thereto, and the ethanol solution was gradually cooled to -20°C for crystallization, filtered and dried to obtain 297g of VA crystals with a purity of ≥98%.

[0057] Example 6

[0058] Add acetylacetonato carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat to 80℃, charge with synthesis gas to a pressure of 4MPaG, maintain the reaction pressure and temperature for 4 hours. After the reaction is over, reduce to room temperature and release the pressure. Perform vacuum distillation at 100PaA, add acetic acid (0.02mol) and sodium acetate (0.04mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat to 120℃, and react for 3 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.52%.

[0059] 567g of 15-carbon phosphine hydrogen sulfate (1.00mol) and 150g of 2-methyl-4-acetoxy-2-butenal are dissolved in 1000g of tetrahydrofuran and heated to 45°C. 560g of sodium hydroxide aqueous solution (1.3mol) is added dropwise thereto, and the dropping speed is controlled so that the reaction temperature does not exceed 45°C. After the addition is completed, keep 45°C and continue the reaction for 2h. After the reaction is completed, 2L of hexane is added to the reaction solution for extraction. After the extract is washed with 1L of water, the solvent is removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers is 95.9%, and the mass content of all-trans vitamin A is 89.8%. 1L of methanol is added thereto, and the methanol solution is gradually cooled to -20°C for crystallization, filtered and dried to obtain 294g of VA crystals with a purity of ≥98%.

[0060] Comparative Example 1

[0061] Add acetylacetonato carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat it to 80°C, charge it with synthesis gas to a pressure of 4MPaG, and maintain the reaction pressure and temperature for 4 hours. After the reaction is over, cool it to room temperature and release the pressure. Perform vacuum distillation at 100PaA, add acetic acid (0.1mol) to the crude 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat it to 120°C, and react for 6 hours. After the reaction is over, take samples for analysis. The sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.35%, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde after refining is <0.01%

[0062] 565g of 15-carbon phosphine dihydrogen phosphate (1.00mol) and 148g of 2-methyl-4-acetoxy-2-butenal are dissolved in 1000g of water and heated to 40°C. 1378g of sodium carbonate aqueous solution (10wt%) is added dropwise thereto, and the dropping speed is controlled so that the reaction temperature does not exceed 40°C. After the dropwise addition is completed, 40°C is maintained and the reaction is continued for 0.5h. After the reaction is completed, 2L of petroleum ether is added to the reaction solution for extraction. After the extract is washed with 1L of water, the solvent is removed to obtain a yellow oily substance, in which the mass content of vitamin A and its isomers is 98.8%, and the mass content of all-trans vitamin A is 78.9%. 1L of ethanol is added thereto, and the ethanol solution is gradually cooled to -20°C for crystallization, filtered and dried to obtain 238g of VA crystals with a purity of ≥97%.

[0063] Comparative Example 2

[0064] Add acetylacetone carbonyl rhodium (1mmol) and 3,4-diacetoxy-1-butene (2mol) into the reactor, heat it to 80℃, charge it with synthesis gas to a pressure of 4MPaG, and maintain the reaction pressure and temperature for 4 hours. After the reaction is over, reduce the temperature to room temperature and release the pressure. Perform vacuum distillation at 100PaA, add acetic acid (0.02mol) and sodium acetate (0.1mol) to the crude product of 2-methyl-3,4-diacetoxybutyraldehyde obtained by distillation, heat it to 100℃, and react for 2 hours. After the reaction is over, take samples for analysis, and the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 2.02%.

[0065] 342g 1,3-bis-double bond pentadecanoic acid ester (1.00mol) and 148g 2-methyl-4-acetoxy-2-butenal were dissolved in 685g methanol and heated to 30°C. 220mL sodium methoxide solution (5mol / L) was added dropwise thereto, and the dropping speed was controlled so that the reaction temperature did not exceed 30°C. After the addition was completed, the temperature was maintained at 30°C and the reaction was continued for 2h. After the reaction was completed, 1L of n-hexane was added to the reaction solution for extraction. After the hexane extract was washed with 0.5L of water, the solvent was removed to obtain a brown-yellow oily substance, in which the mass content of vitamin A and its isomers was 82.6%, and the mass content of all-trans vitamin A was 98%. 0.5L of methanol was added thereto, and the methanol solution was gradually cooled to -20°C for crystallization, filtered and dried to obtain 206g of VA crystals with a purity of ≥96%.

[0066] Any modification or equivalent replacement of the technical solution of the present invention, which does not depart from the scope of the technical solution of the present invention, should be included in the protection scope of the present invention.

Claims

1. A method for preparing vitamin A, characterized in that: Vitamin A is prepared by reacting a pentadecanphosphonate or a pentadecanphosphonate with 2-methyl-4-acetoxy-2-butenal and a base, wherein the sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.02% to 0.8%; Among them, the structure of 2-methyl-4-acetoxy-2-butenal is The structure of 2-methyl-3,4-diacetoxybutyraldehyde is The structure of 2-methyl-3-acetoxy-3-butene-1-aldehyde is 2. The preparation method according to claim 1, characterized in that: The sum of the contents of 2-methyl-3,4-diacetoxybutyraldehyde and 2-methyl-3-acetoxy-3-butene-1-aldehyde in 2-methyl-4-acetoxy-2-butenal is 0.1% to 0.5%.

3. The preparation method according to claim 1, characterized in that: 2-Methyl-4-acetoxy-2-butenal is synthesized by the following method: (a) 3,4-diacetyl-1-butene undergoes a hydroformylation reaction in the presence of a rhodium catalyst to generate 2-methyl-3,4-diacetoxybutyraldehyde; (b) 2-methyl-3,4-diacetoxybutyraldehyde reacts in the presence of acetic acid and sodium acetate to generate 2-methyl-4-acetoxy-2-butenal.

4. The preparation method according to claim 3, characterized in that: The rhodium catalyst is acetylacetonato carbonyl rhodium, and the amount of the rhodium catalyst used is 0.01% to 0.1% of the molar amount of 3,4-diacetoxy-1-butene calculated as rhodium atom.

5. The preparation method according to claim 3, characterized in that: In the step (a), the reaction pressure is 2-4 MPa, the reaction temperature is 60-100° C., and the reaction time is 2-4 hours.

6. The preparation method according to claim 3, characterized in that: In the step (b), the amount of acetic acid used is 1% to 5% of the molar amount of 2-methyl-3,4-diacetoxybutyraldehyde, the amount of sodium acetate used is 1% to 5% of the molar amount of 2-methyl-3,4-diacetoxybutyraldehyde, the molar ratio of acetic acid to sodium acetate is 0.5:1 to 2:1, the reaction temperature is 100 to 120° C., and the reaction time is 2 to 4 hours.

7. The preparation method according to claim 1, characterized in that: Pentadecylphosphonate is R is an alkyl group of 1 to 6 carbon atoms.

8. The preparation method according to claim 7, characterized in that: Pentadecylphosphonate is 9. The preparation method according to claim 1, characterized in that: Pentadecylphosphine salt is One or more of .

10. The preparation method according to any one of claims 1 to 3, characterized in that: The molar ratio of the pentadecylphosphonate or phosphonium salt to 2-methyl-4-acetoxy-2-butenal is 1:1 to 1:1.

1.

11. The preparation method according to claim 1, characterized in that: The base is one or more of alkali metal hydrides, alkali metal amides, alkali metal alkyls, alkali metal hydroxides, alkali metal alkoxides, and alkali metal carbonates.

12. The preparation method according to claim 11, characterized in that: The alkali is one or more of sodium hydroxide, sodium methoxide and sodium carbonate.

13. The preparation method according to claim 1, characterized in that: The molar ratio of the base to the pentadecylphosphonate or phosphonium salt is 1.1:1 to 1.3:

1.

14. The preparation method according to claim 1, characterized in that: The reaction temperature is 30-60°C.

15. The preparation method according to claim 1, characterized in that: The solvent is one or more of water, methanol, tetrahydrofuran, dioxane, dimethoxyethane and N,N-dimethylformamide.

16. The preparation method according to claim 1, characterized in that: The amount of solvent used is 2 to 3 times the mass of the pentadecanophosphonate or phosphonium salt.

17. The preparation method according to claim 1, characterized in that: Reaction time: 0.5~2h.

18. The preparation method according to any one of claims 1 to 5, characterized in that: After the reaction is completed, hexane, heptane or petroleum ether is used for extraction, and the extract is washed with water and the solvent is removed to obtain crude vitamin A; the crude vitamin A is crystallized using methanol or ethanol to obtain a vitamin A product.

Images