A kind of preparation method of phosphonate composition and vitamin A acetate

Abstract

The present invention discloses a phosphonium salt composition and a method for preparing vitamin A acetate. In the phosphonium salt composition, the mass content of compound (1) is 0.1-5%, the mass content of compound (2) is 1-10%, the mass content of compound (3) is 0.1-5%, and the mass content of C15 phosphonium salt is 80-98.8%. Vitamin A acetate is prepared by using the C15 phosphonium salt of the present invention, and the selectivity is high. Vitamin A acetate has good thermal stability and good corrosion resistance.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of a phosphonium salt composition and vitamin A acetate. Background Art

[0002] Vitamin A acetate is an important substance used in the fields of medicine and cosmetics, food and food supplements, animal nutrition feed additives, etc. Vitamin A acetate is generally prepared by Wittig reaction in industry.

[0003] The following problems exist in the preparation of vitamin A acetate by Wittig reaction: (1) Low yield. Patents JP06329623, CN101318975, CN101219983 and CN102190565 all report that the product vitamin A acetate is obtained by Wittig reaction with complicated post-processing steps, and the actual yield is about 80%. (2) Very poor cis-trans selectivity. Patent CN103044302 reports a one-pot method for preparing vitamin A acetate, which uses C14 aldehyde and intermediate C1 ester to generate C15 phosphonate under alkaline conditions. The reaction generates more phosphate isomers, and the cis-trans selectivity of the VA acetate obtained by the subsequent Wittig reaction is poor. Patent CN1894208A obtains the Wittig reagent precursor (β-ionylethyl triphenylphosphonium salt) by reacting vinyl ionol with triphenylphosphine in the presence of sulfuric acid. During the reaction, a large amount of isomeric impurities are generated due to the difficulty in controlling the reaction temperature, and the product is difficult to crystallize and separate. (3) Vitamin A has poor thermal stability. In the intermittent process, if the Wittig reaction time is too long or the temperature fluctuates too much, vitamin A acetate will be dehydrated in an alkaline environment, generating vitamin A dehydrate products that are extremely difficult to remove, affecting the purity of the product and limiting its application in high-end fields. (4) The material has high corrosion resistance requirements and large investment. The Wittig reaction temperature of the equipment is generally above 70°C, and a strong alkaline solution is used. The raw material phosphine salt is a highly corrosive organic matter, which is easy to cause alkaline embrittlement corrosion to the equipment and pipeline materials. Therefore, the materials commonly used to produce vitamin A are generally TA materials, Hastelloy, etc., and the equipment investment is extremely large. (5) The amount of wastewater is large and difficult to treat. The Wittig reaction uses a strong alkaline aqueous solution. After the product is extracted with an organic solvent, a large amount of inorganic biochemical wastewater is generated, which has high salt content and high COD characteristics. The investment in treating Wittig wastewater is extremely high.

[0004] As can be seen from the above, the preparation of vitamin A acetate by Wittig reaction is a research hotspot, but there is a huge room for improvement. Therefore, finding a low-cost preparation process becomes the key to the problem. Summary of the invention

[0005] The invention provides a phosphonium salt composition and a preparation method of vitamin A acetate, thereby solving the problems of low yield, extremely poor cis-trans selectivity, poor thermal stability of vitamin A acetate, high requirements for material corrosion resistance, etc. in the synthesis of vitamin A acetate.

[0006] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0007] A phosphonium salt composition comprises a compound (1), a compound (2), a compound (3) and a C15 phosphonium salt, wherein the structural formula of the compound (1) is:

[0008]

[0009] The structural formula of compound (2) is:

[0010]

[0011] The structural formula of compound (3) is:

[0012]

[0013] The structural formula of the C15 phosphonate is:

[0014]

[0015] In the phosphine salt composition, the mass content of compound (1) is 0.1-5%, preferably 1-2%; the mass content of compound (2) is 1-10%, preferably 2-6%; the mass content of compound (3) is 0.1-5%, preferably 1-3%; the mass content of C15 phosphine salt is 80-98.8%, preferably 89-96%.

[0016] The C15 phosphonium salt composition described in the present application is a mixture of existing C15 phosphonium salt and compounds (1), (2) and (3). The phosphonium salt composition described in the present invention is used to prepare vitamin A acetate, which has high selectivity, good thermal stability, less three wastes, and low corrosion resistance requirements for process materials.

[0017] In a second aspect, the present application provides a method for preparing vitamin A acetate, which uses a C15 phosphine salt composition and a C5 aldehyde as raw materials to produce vitamin A acetate under the action of a catalyst.

[0018] Preferably, the structure of the C5 aldehyde is:

[0019]

[0020] Furthermore, in the preparation method of vitamin A acetate, a mixed solution of a C15 phosphine salt composition and a C5 aldehyde is prepared in a raw material tank, and a catalyst solution of a certain concentration is prepared in another raw material tank. The two streams of materials are preheated in a mixer and then enter a reactor to react and generate vitamin A acetate.

[0021] After the reaction is completed, the material at the reaction outlet is extracted with an extractant at a certain temperature and centrifuged to obtain a product organic phase, and then the solvent is removed to obtain vitamin A acetate.

[0022] After the system has been running stably for a long time, samples are taken to analyze the product yield, all-trans content and thermal stability, and the equipment corrosion rate and wastewater discharge are calculated.

[0023] Preferably, the molar ratio of C15 phosphine salt to C5 aldehyde in the C15 phosphine salt composition is 1:(0.5-5), preferably 1:(1-2).

[0024] Preferably, the dissolved C15 phosphine salt composition and C5 aldehyde are configured into a solution by a solvent, and the solvent is one or more of methanol, ethanol, toluene, water, ethyl acetate, dichloromethane, acetone, etc., preferably water;

[0025] Preferably, the mass percentage of C15 phosphine salt in the mixed solution 1 is 30-90wt%, preferably 50wt%-70wt%.

[0026] Preferably, the catalyst is a metal carbonate, preferably an alkali metal carbonate, including any one or a combination of at least two of sodium carbonate, potassium carbonate or lithium carbonate, preferably potassium carbonate. The catalyst is an aqueous solution of carbonate, and the mass percentage of carbonate is 10-90wt%, preferably 25wt%-70wt%.

[0027] Preferably, the molar ratio of the C15 phosphine salt to the catalyst in the C15 phosphine salt composition is 1:(0.5-5), preferably 1:(1-2).

[0028] Preferably, the preheating temperature is 30-60°C, preferably 38-45°C.

[0029] Preferably, the reaction temperature is 10-80°C, preferably 35-63°C.

[0030] Preferably, the residence time of the reaction is 0.1-4 h, preferably 1-3 h.

[0031] Preferably, the reaction pressure is 0.01-1.0 MPa, preferably 0.1-0.5 MPa.

[0032] Preferably, the reaction outlet material is cooled to 0-20°C, preferably 10-15°C, and the extractant is one or more of n-hexane, toluene, m-xylene, p-xylene, n-heptane, n-pentane, benzene, and cyclohexane, preferably n-heptane.

[0033] The inventors surprisingly found that: first, by adding compound (1) to pure phosphine salt crystals, the solubility of phosphine salt in solvent can be increased, so that phosphine salt can be evenly distributed in a small solvent system, and mass transfer can be increased to inhibit the occurrence of side reactions; second, by adding compound (2) to pure phosphine salt crystals, the effect of inhibiting the activity of Wittig reaction can be improved, so that the reaction occurs gently without local overheating; third, by adding compound (3) to pure phosphine salt crystals, the effect of isomerization inhibitor can be achieved, thereby increasing the all-trans content of the product.

[0034] Therefore, the use of the phosphonium salt composition of the present invention to prepare vitamin A acetate can solve the problems of low yield, extremely poor cis-trans selectivity, and poor thermal stability of vitamin A in the synthesis of vitamin A acetate from the raw material end.

[0035] Moreover, the use of the phosphonium salt composition of the present invention can solve the problems of high material corrosion resistance requirements and large amount of catalyst used in the traditional process of synthesizing vitamin A acetate, which leads to wastewater. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is the H NMR spectrum of compound (1);

[0037] Figure 2 is the NMR carbon spectrum of compound (1);

[0038] Figure 3 is the H NMR spectrum of compound (2);

[0039] Figure 4 is the NMR carbon spectrum of compound (2);

[0040] Figure 5 is the H NMR spectrum of compound (3);

[0041] Figure 6 is the C NMR spectrum of compound (3). DETAILED DESCRIPTION

[0042] The methanol, potassium carbonate, 3,7-dimethyl-2,6-octadienal used in the present invention 6,10-Dimethyl-3,5,9-undecatrien-2-one and 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one etc. were purchased from Shanghai Titan Technology Co., Ltd., C5 aldehyde Purchased from BASF Chemical Co., Ltd.

[0043] In the embodiments of the present invention, the content and purity of each component are tested and calculated by the external standard method of high performance liquid chromatograph (Shimadzu LC-20AD), and the conversion rate is calculated based on the content of the product; the liquid chromatography conditions are as follows: chromatographic column: WAters XSelect HSS T3, 4.6 μm×250 mm; injection volume: 2 to 10 μL, fine-tuned according to the sample conditions; column temperature: 40° C.; flow rate: 1 mL / min; detector: ultraviolet detector (UV), detection wavelength of 254 to 400 nm; mobile phase: acetonitrile / 0.1% phosphoric acid aqueous solution; when measuring the sample, first establish a liquid phase external standard curve with a pure product, and calculate the mass fraction (content) of each test substance based on the linear relationship between concentration and liquid phase peak area.

[0044] The thermal stability of the product in the embodiment of the present invention is measured by an advanced fully automatic laboratory reaction calorimeter developed by Ciba-Geigy of Switzerland, referred to as an adiabatic reaction calorimeter, model IGG-RC1e, which can monitor the instantaneous heat release power of the reaction process and determine the thermal stability of the product.

[0045] The tubular reactor in the present invention is an adiabatic reactor, the equipment is made of 304 material, the reactor length is 7.62m, the inner radius is 50.8mm, the wall thickness is 5mm, and the pressure drop is 0. The corrosion rate calculation formula of the equipment material (only the reactor material is used as an example for explanation) in the embodiment of the present invention is as follows:

[0046]

[0047] Where: △m—equipment mass loss, g; s—equipment surface area, cm 2 ; ρ—density of equipment material, g / cm 3 ; t—experiment duration, h.

[0048] The specific embodiments are as follows: In the process of the present invention, the preparation of C15 phosphonium salt, compounds (1), (2), and (3) all adopt the following preparation method.

[0049] C15 Phosphonate The raw materials are homemade, and the preparation method of C15 phosphine salt refers to the prior art, and refers to CN109651150A, which is specifically as follows:

[0050] 264.5 g, 1.01 mol of triphenylphosphine and 96.8 g, 38 wt %, 1.01 mol of hydrochloric acid were added to a reactor; after replacement with CO2 for 3 times, CO2 gas was charged into the reactor and stirring was started, the temperature in the high-pressure reactor was increased to 45° C., and the pressure in the reactor was maintained at 14 MPa by a pressure regulating valve, and 220 g, 1 mol of vinyl-β-ionol was pumped into the reactor by a horizontal flow pump for reaction to prepare C15 phosphonate with a liquid chromatography purity of about 98.5%.

[0051] Recrystallization purification: Take 98.5% of the C15 phosphine salt obtained above, add ethyl acetate twice the mass of the C15 phosphine salt, heat to 77°C to dissolve, and then quickly cool the resulting mixture to 0°C and filter and dry to obtain 100% C15 phosphine salt crystals. The product appears as white needle-shaped particles.

[0052] Preparation of compound (1): 30 g of 3,7-dimethyl-2,6-octadienal and 300.00 g of acetone were added to a 0.5 L reactor under nitrogen atmosphere. After stirring, the reaction temperature was raised to 90°C. 100 g of a 30% aqueous solution of NaOH was added dropwise. After reacting for 2 to 4 hours, the solvent was removed to obtain compound (1). The purity of the compound (1) was 96.7% by liquid chromatography analysis. Figure 1 is the H NMR spectrum of compound (1), attached Figure 2 This is the carbon NMR spectrum of the synthesized compound (1).

[0053] Analysis of the spectrum of compound (1): In the carbon nuclear magnetic resonance spectrum, the chemical shifts of 18.6 and 24.6 are methyl carbon (-CH3) shift response peaks, of which the shift peak intensity of 24.6 is twice that of 18.6, proving that the molecular structure contains three -CH3 functional groups and two of them have the same structural position. The chemical shifts of 26.1 and 33.2 are methylene carbon (-CH2) shift response peaks, indicating that the system contains two -CH2, the chemical shifts of 123.5 and 127.8 are -CH carbon peaks, indicating that the system contains two -CH, the chemical shifts of 132 and 162 are -C carbon peaks, and the system may contain two carbon-carbon double bonds without hydrogen atoms. Corresponding to the nuclear magnetic resonance hydrogen spectrum, the chemical shifts of 5.2 and 5.7 are -CH on the carbon-carbon double bond, 1.7-1.8 are the hydrogen spectrum peaks corresponding to the three methyl groups, 2.0 is the peak corresponding to -CH2, and the chemical shift of 9.68 corresponds to the hydrogen on the aldehyde group.

[0054] From the above, we can see that the H-NMR spectrum and C-NMR spectrum can correspond well to the molecular structure shown.

[0055] The spectra of the following compounds (2) and (3) involved in this patent can all be compared and analyzed using the above-mentioned analytical method to confirm the molecular structure of the synthesized substance. Since technicians in this field can know the obtained molecular structure from the nuclear magnetic resonance spectrum through the chemical knowledge they have learned, the proof will not be repeated.

[0056] Preparation of compound (2): A 10 wt % dichloromethane solution of 6,10-dimethyl-3,5,9-undecatrien-2-one was added to a 0.5 L reactor under a nitrogen atmosphere, stirring was started and the reaction temperature was controlled to 30° C. A 5 wt % H2SO4 aqueous solution was added thereto under normal pressure, and the mixture was kept warm for 3 h and then allowed to stand for stratification. The solvent was removed from the obtained organic phase to obtain compound (2). The purity of the obtained compound by liquid chromatography was 98.7%. Figure 3 The H NMR spectrum of the synthesized compound (2) is shown in Figure 2. Figure 4 is the C NMR spectrum of compound (2).

[0057] Preparation of compound (3): Add 100g of 18wt% vinyl magnesium chloride tetrahydrofuran solution to a dry 0.5L reactor under nitrogen atmosphere, start stirring and control the reactor temperature to 40°C, then add 50g of 20wt% 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-butene-2-one, stir at high speed and keep warm for 5h. After the reaction, lower the temperature of the reactor by 5°C and add 10% acetic acid aqueous solution. Filter and collect the liquid phase, remove the solvent from the organic phase after phase separation to obtain compound (3), with a liquid chromatography purity of 99.2%. Figure 5 and the H NMR spectra of compound (3), attached Figure 6 is the C NMR spectrum of compound (4).

[0058] Embodiment 1:

[0059] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) and C15 phosphonium salt crystals are mixed under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of the phosphonium salt composition, the mass content of compound (1) is 1.0%, the mass content of compound (2) is 2.0%, the mass content of compound (3) is 3.0%, and the mass content of C15 phosphonium salt is 94.0%.

[0060] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare an aqueous solution of a phosphonate composition and a pentaldehyde (wherein the molar ratio of C15 phosphonate to pentaldehyde is 1:1, and the mass concentration of C15 phosphonate in the mixed solution is 50.0wt%) in a raw material tank, and prepare a 33wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1, preheated to 38°C, and then injected into a tubular reactor through a flowmeter at a molar flow rate of C15 phosphonate of 1 mol / min (i.e., the reaction residence time is controlled to be 2.2h), and the reaction pressure is 0.1MPaG. After the system is stabilized, samples are taken for analysis and the C15 phosphonate conversion rate is 100%.

[0061] After the temperature of the reaction outlet material is lowered to 10°C, n-heptane is added for extraction, and the phases are separated by centrifugation to obtain a wastewater phase and an organic phase, respectively. The organic phase is then desolventized to obtain the product vitamin A acetate. The calculated wastewater is 0.85 g / g vitamin A acetate, which is 3.3 times less than the calculated wastewater of 2.83 g / g vitamin A acetate in Example 1 of patent CN100455558C, and its production investment is greatly reduced.

[0062] Analysis shows that the highest temperature of the reactor during the experiment was 61°C, and the maximum heat release rate of the wittig reaction was 120 W. It can be seen that the heat release rate of the reaction under this process is extremely slow, and local high temperature will not be formed. After the device has been running for 720 hours, the corrosion rate of the equipment material is less than 0.01mm / a, which proves that the equipment with 304 material (20 yuan / kg) can also perform the wittig reaction to generate vitamin A acetate, which is 10 times cheaper than the traditional wittig reaction process material HC276 (200 yuan / kg), and its production investment is greatly reduced.

[0063] The analysis showed that the selectivity of vitamin A acetate was stable at 99.5%, and the proportion of all-trans isomers was as high as 85%. The runaway time of vitamin A acetate obtained by IGG-RC1e analysis was 24 hours, and the corresponding initial temperature was 70°C, indicating that the product was very stable under this process and would not have heat sensitivity and heat safety issues.

[0064] Embodiment 2:

[0065] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) are mixed with C15 phosphonium salt crystals under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of the phosphonium salt composition, the mass content of compound (1) is 2.0%, the mass content of compound (2) is 3.0%, the mass content of compound (3) is 3.0%, and the mass content of C15 phosphonium salt is 92.0%.

[0066] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare a phosphonate composition and an aqueous solution of five carbon aldehydes in a raw material tank (wherein the molar ratio of C15 phosphonate to five carbon aldehydes is 1:1.2, and the mass concentration of C15 phosphonate in the mixed solution is 55.0wt%), and prepare a 25wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1.2 to 40°C, and then injected into a tubular reactor through a flow meter at a molar flow rate of C15 phosphonate of 2.2 mol / min (i.e., the reaction residence time is controlled to be 1.0h), and the reaction pressure is 0.2MPaG. After the system is stabilized, samples are taken for analysis, and the conversion rate of C15 phosphonate is 99.5%.

[0067] After lowering the temperature of the reaction outlet material to 11°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater is 0.90g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 60°C, the maximum exothermic rate of the wittig reaction was 119W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 99.2%, and the proportion of all-trans body was 85%. The out-of-control time of vitamin A acetate obtained by IGG-RC1e analysis was 24h, and the initial temperature corresponding to it was 69°C, and there would be no heat sensitivity and thermal safety problems.

[0068] Embodiment 3:

[0069] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) are mixed with C15 phosphonium salt crystals under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of phosphonium salt composition, the content of compound (1) is 2.0%, the content of compound (2) is 5.0%, the content of compound (3) is 3.0%, and the content of C15 phosphonium salt is 90.0%.

[0070] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare a phosphonate composition and an aqueous solution of five carbon aldehydes in a raw material tank (wherein the molar ratio of C15 phosphonate to five carbon aldehydes is 1:1.4, and the mass concentration of C15 phosphonate in the mixed solution is 60.0wt%), and prepare a 40wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1.4 to 42°C, and then injected into a tubular reactor through a flow meter at a molar flow rate of C15 phosphonate of 1.1 mol / min (i.e., the reaction residence time is controlled to be 2.0h), and the reaction pressure is 0.3MPaG. After the system is stabilized, samples are taken for analysis and the C15 phosphonate conversion rate is 100%.

[0071] After lowering the temperature of the reaction outlet material to 12°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater is 1.0g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 59°C, the maximum exothermic rate of the wittig reaction was 116W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 99.3%, and the proportion of all-trans body was 83.6%. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24h, and the initial temperature corresponding to it was 68°C, and there would be no heat sensitivity and thermal safety problems.

[0072] Embodiment 4:

[0073] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. C15 phosphonium salt crystals are added to compounds (1), (2) and (3) under nitrogen atmosphere and mixed to prepare phosphonium salt composition. Wherein, based on the mass of C15 phosphonium salt composition, the mass content of compound (1) is 2.0%, the mass content of compound (2) is 6.0%, the mass content of compound (3) is 3.0%, and the mass content of C15 phosphonium salt is 89.0%.

[0074] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare a phosphonate composition and an aqueous solution of five carbon aldehydes in a raw material tank (wherein the molar ratio of C15 phosphonate to five carbon aldehydes is 1:1.6, and the mass concentration of C15 phosphonate in the mixed solution is 65.0wt%), and prepare a 50wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1.6 to 42°C, and then injected into a tubular reactor through a flow meter at a molar flow rate of C15 phosphonate of 1.1 mol / min (i.e., the reaction residence time is controlled to be 2.0h), and the reaction pressure is 0.1MPaG. After the system is stabilized, samples are taken for analysis, and the C15 phosphonate conversion rate is 99.1%.

[0075] After lowering the temperature of the reaction outlet material to 12°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater is 1.0g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 59°C, the maximum exothermic rate of the wittig reaction was 114W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 99.4%, and the proportion of all-trans body was 85%. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24h, and the initial temperature corresponding to it was 71.3°C, and there would be no heat sensitivity and thermal safety problems.

[0076] Embodiment 5:

[0077] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) are mixed with C15 phosphonium salt crystals under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of the phosphonium salt composition, the content of compound (1) is 1.0%, the content of compound (2) is 2.0%, the content of compound (3) is 1.0%, and the content of C15 phosphonium salt is 96.0%.

[0078] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare a phosphonate composition and an aqueous solution of five carbon aldehydes in a raw material tank (wherein the molar ratio of C15 phosphonate to five carbon aldehydes is 1:2.0, and the mass concentration of C15 phosphonate in the mixed solution is 70.0wt%), and prepare a 50wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:2.0 to 45°C, and then injected into a tubular reactor through a flow meter at a molar flow rate of C15 phosphonate of 0.73mol / min (i.e., the reaction residence time is controlled to be 3.0h), and the reaction pressure is 0.5MPaG. After the system is stabilized, samples are taken for analysis and the C15 phosphonate conversion rate is 100%.

[0079] After lowering the temperature of the reaction outlet material to 15°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater was 1.2g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 61°C, the maximum exothermic rate of the wittig reaction was 119W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 99.6%, and the proportion of all-trans body was 85.6%. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24h, and the initial temperature corresponding to it was 72°C, and there would be no heat sensitivity and thermal safety problems.

[0080] Embodiment 6:

[0081] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) and C15 phosphonium salt crystals are mixed under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of the phosphonium salt composition, the mass content of compound (1) is 0.1%, the mass content of compound (2) is 1.0%, the mass content of compound (3) is 0.1%, and the mass content of C15 phosphonium salt is 98.8%.

[0082] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare an aqueous solution of a phosphonate composition and a pentaldehyde (wherein the molar ratio of C15 phosphonate to pentaldehyde is 1:1, and the mass concentration of C15 phosphonate in the mixed solution is 50.0wt%) in a raw material tank, and prepare a 33wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1, preheated to 38°C, and then injected into a tubular reactor through a flowmeter at a molar flow rate of C15 phosphonate of 1 mol / min (i.e., the reaction residence time is controlled to be 2.2h), and the reaction pressure is 0.1MPaG. After the system is stabilized, samples are taken for analysis and the C15 phosphonate conversion rate is 100%.

[0083] After lowering the temperature of the reaction outlet material to 10°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater is 1.1g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 61°C, the maximum exothermic rate of the wittig reaction was 119W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 99.2%, and the proportion of all-trans body was 80.6%. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24h, and the initial temperature corresponding to it was 71°C, and there would be no heat sensitivity and thermal safety problems.

[0084] Embodiment 7:

[0085] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. Compounds (1), (2) and (3) and C15 phosphonium salt crystals are mixed under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of the phosphonium salt composition, the mass content of compound (1) is 0.1%, the mass content of compound (2) is 1.0%, the mass content of compound (3) is 0.1%, and the mass content of C15 phosphonium salt is 98.8%.

[0086] Preparation of vitamin A acetate: Under nitrogen atmosphere, prepare an aqueous solution of a phosphonate composition and a pentaldehyde (wherein the molar ratio of C15 phosphonate to pentaldehyde is 1:1, and the mass concentration of C15 phosphonate in the mixed solution is 50.0wt%) in a raw material tank, and prepare a 33wt% potassium carbonate aqueous solution in another raw material tank. The two raw materials are quickly mixed in a mixer at a molar ratio of C15 phosphonate to potassium carbonate of 1:1, preheated to 38°C, and then injected into a tubular reactor through a flowmeter at a molar flow rate of C15 phosphonate of 1 mol / min (i.e., the reaction residence time is controlled to be 2.2h), and the reaction pressure is 0.1MPaG. After the system is stabilized, samples are taken for analysis and the C15 phosphonate conversion rate is 100%.

[0087] After lowering the temperature of the reaction outlet material to 10°C, n-heptane was added for extraction and centrifugal filtration to separate the phases, and the wastewater phase and the organic phase were obtained respectively. The organic phase was then desolventized to obtain the product vitamin A acetate. The calculated wastewater was 1.3g / g vitamin A acetate. During the experiment, the highest temperature of the reactor was 61°C, the maximum exothermic rate of the wittig reaction was 119W, and the corrosion rate of the equipment material after 720h was less than 0.01mm / a. The selectivity of vitamin A acetate was stable at 98.5%, and the proportion of all-trans body was 86.6%. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24h, and the initial temperature corresponding to it was 70°C, and there would be no heat sensitivity and thermal safety problems.

[0088] Comparative Example 1:

[0089] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. C15 phosphonium salt crystals are added to compounds (1), (2) and (3) under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of phosphonium salt composition, the mass content of compound (1) is 0.05%, the mass content of compound (2) is 0.05%, the mass content of compound (3) is 0.05%, and the mass content of C15 phosphonium salt is 99.85%.

[0090] Preparation of Vitamin A Acetate: The preparation of Vitamin A Acetate is exactly the same as that in Example 1.

[0091] The analysis shows that the conversion rate of C15 phosphine salt is 100%, and the maximum exothermic rate of the Wittig reaction is 1.2kW. It can be seen that the exothermic rate of the reaction is fast under this process, and it is easy to form local high temperature at the inlet section of the reactor. After the device has been running for 720 hours, the corrosion rate of the equipment material is 1.12mm / a, and the corrosion is relatively serious.

[0092] The analysis showed that the selectivity of vitamin A acetate was 92.3%, the all-trans isomer accounted for only 55%, and the biological activity was greatly reduced.

[0093] Comparative Example 2:

[0094] Preparation of phosphonium salt composition: C15 phosphonium salt crystals, compound (1), compound (2) and compound (3) are prepared respectively according to the above method. C15 phosphonium salt crystals are added to compounds (1), (2) and (3) under nitrogen atmosphere to prepare phosphonium salt composition. Wherein, based on the mass of C15 phosphonium salt, the content of compound (1) is 6.0%, the content of compound (2) is 12.0%, the content of compound (3) is 6.0%, and the content of C15 phosphonium salt is 76.0%.

[0095] Preparation of Vitamin A Acetate: The preparation of Vitamin A Acetate is exactly the same as that in Example 1.

[0096] The analysis showed that the conversion rate of C15 phosphine salt was 79%, the highest temperature of the reactor during the experiment was 54°C, and the maximum exothermic rate of the Wittig reaction was 96W.

[0097] The analysis showed that the selectivity of vitamin A acetate was 98.5%, and the single-pass yield of the product was 77.8%, which was extremely low. The IGG-RC1e analysis showed that the out-of-control time of vitamin A acetate was 24 hours, and the initial temperature corresponding to it was 58°C, while the highest temperature of the reactor during the experiment was 54°C. If the equipment is operated for a long time, vitamin A acetate will undergo secondary reactions, causing safety risks and product deterioration, which is extremely unfavorable for industrial production.

[0098] Comparative Example 3:

[0099] In order to improve the yield in Comparative Example 2, the method is to increase the conversion rate of the raw materials, so the amount of the catalyst is increased. The specific experimental steps are as follows:

[0100] Preparation of the phosphonium salt composition: the same as that of Comparative Example 2.

[0101] Preparation of vitamin A acetate: Only the mass percentage of the prepared potassium carbonate was increased from 33wt% to 58wt%. The other preparation processes of vitamin A acetate were the same as those of vitamin A acetate in Example 1.

[0102] The analysis showed that the conversion rate of C15 phosphine salt was 99.5%. During the experiment, the highest temperature of the reactor was 60°C, and the amount of alkali solution increased by 1.8 times.

[0103] From comparative example (1), it can be seen that the content of compounds (1)-(3) is small, the Wittig reaction rate is fast, the conversion of all-trans to cis is fast, the biological activity of the product is greatly reduced, and the reaction rate is fast, the instantaneous heat release power of the reaction is large, and there is local high temperature inside the reactor, which is easy to cause equipment corrosion;

[0104] It can be seen from Comparative Examples (2) and (3) that the content of compounds (1)-(3) is high, the yield of vitamin A is low, and the thermal stability of the product is poor. In order to achieve the same process yield, the amount of alkali solution (catalyst) increased by 1.8 times, resulting in a huge amount of three wastes.

Claims

1. A phosphonium salt composition comprising compound (1), compound (2), compound (3) and a C15 phosphonium salt, wherein the structural formula of compound (1) is: The structural formula of compound (2) is: The structural formula of compound (3) is: The structural formula of the C15 phosphonate is: In the phosphonium salt composition, the mass content of compound (1) is 0.1-5%, the mass content of compound (2) is 1-10%, the mass content of compound (3) is 0.1-5%, and the mass content of C15 phosphonium salt is 80-98.8%.

2. The phosphonium salt composition according to claim 1, characterized in that In the phosphine salt composition, the mass content of compound (1) is 1-2%; the mass content of compound (2) is 2-6%; the mass content of compound (3) is 1-3%, and the mass content of C15 phosphine salt is 89-96%.

3. A method for preparing vitamin A acetate, characterized in that: Using the C15 phosphonate composition according to claim 1 or 2 and C5 aldehyde as raw materials in the presence of a catalyst to produce vitamin A acetate; The structure of the C5 aldehyde is:

4. The preparation method according to claim 3, characterized in that: A mixed solution of C15 phosphine salt composition and C5 aldehyde is prepared in a raw material tank, and a catalyst solution is prepared in another raw material tank. The two streams of materials are preheated in a mixer and then enter a reactor to react and generate vitamin A acetate.

5. The preparation method according to claim 3 or 4, characterized in that: After the reaction is completed, the material at the reaction outlet is extracted with an extractant and centrifuged to obtain a product organic phase, and then the solvent is removed to obtain vitamin A acetate.

6. The preparation method according to claim 3 or 4, characterized in that: The molar ratio of the C15 phosphine salt to the C5 aldehyde in the C15 phosphine salt composition is 1:(0.5-5).

7. The preparation method according to claim 6, characterized in that: The molar ratio of the C15 phosphine salt to the C5 aldehyde in the C15 phosphine salt composition is 1:(1-2).

8. The preparation method according to claim 3 or 4, characterized in that: The C15 phosphine salt composition and C5 aldehyde are configured into a solution by using a solvent, and the solvent is one or more of methanol, ethanol, toluene, water, ethyl acetate, dichloromethane, and acetone.

9. The preparation method according to claim 8, characterized in that: The solvent is water.

10. The preparation method according to claim 4, characterized in that: The mass percentage of C15 phosphonate in the mixed solution 1 is 30-90wt%.

11. The preparation method according to claim 10, characterized in that: The mass percentage of C15 phosphonate in the mixed solution 1 is 50wt%-70wt%.

12. The preparation method according to claim 3 or 4, characterized in that: The catalyst is a metal carbonate.

13. The preparation method according to claim 12, characterized in that: The catalyst is an alkali metal carbonate.

14. The preparation method according to claim 13, characterized in that: The catalyst is any one of sodium carbonate, potassium carbonate or lithium carbonate, or a combination of at least two of them.

15. The preparation method according to claim 12, characterized in that: The catalyst is an aqueous solution of carbonate, and the mass percentage of carbonate is 10-90wt%.

16. The preparation method according to claim 3 or 4, characterized in that: The molar ratio of the C15 phosphine salt to the catalyst in the C15 phosphine salt composition is 1:(0.5-5).

17. The preparation method according to claim 16, characterized in that: The molar ratio of the C15 phosphine salt to the catalyst in the C15 phosphine salt composition is 1:(1-2).

18. The preparation method according to claim 4, characterized in that: The preheating temperature is 30-60℃.

19. The preparation method according to claim 18, characterized in that: The preheating temperature is 38-45℃.

20. The preparation method according to claim 4, characterized in that: The reaction temperature is 10-80°C.

21. The preparation method according to claim 20, characterized in that: The temperature of the reaction is 35-63°C.

22. The preparation method according to claim 4, characterized in that: The residence time of the reaction is 0.1-4h.

23. The preparation method according to claim 22, characterized in that: The residence time of the reaction is 1-3 h.

24. The preparation method according to claim 4, characterized in that: The reaction pressure is 0.01-1.0 MPa.

25. The preparation method according to claim 24, characterized in that: The reaction pressure is 0.1-0.5 MPa.

26. The preparation method according to claim 5, characterized in that: The reaction outlet material is cooled to 0-20°C.

27. The preparation method according to claim 26, characterized in that: The reaction outlet material is cooled to 10-15°C.

28. The preparation method according to claim 5, characterized in that: The extractant is one or more of n-hexane, toluene, m-xylene, p-xylene, n-heptane, n-pentane, benzene and cyclohexane.

29. The preparation method according to claim 28, characterized in that: The extractant is n-heptane.

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