CN112457229B - Preparation method of vitamin A acetate - Google Patents

Preparation method of vitamin A acetate Download PDF

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CN112457229B
CN112457229B CN202011374517.9A CN202011374517A CN112457229B CN 112457229 B CN112457229 B CN 112457229B CN 202011374517 A CN202011374517 A CN 202011374517A CN 112457229 B CN112457229 B CN 112457229B
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刘英瑞
孔令晓
李莉
高洪坤
郭劲资
张涛
吕英东
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Wanhua Chemical Group Co Ltd
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    • C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
    • C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
    • C07C403/12—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms by esterified hydroxy groups
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    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/48—Preparation of compounds having groups
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    • C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
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Abstract

The invention provides a preparation method of vitamin A acetate, which comprises the following steps: the process provides a C13+ C7 vitamin A acetate synthesis route, improves the yield of the vitamin A acetate, reduces the process cost and is more beneficial to industrial production.

Description

Preparation method of vitamin A acetate
Technical Field
The invention relates to a preparation method of vitamin A acetate, and particularly relates to a method for preparing vitamin A acetate by utilizing a Wittig reaction.
Background
Vitamin A acetate is an important nutritional chemical, has effects of promoting growth and development of human body, and enhancing disease resistance.
The vitamin A acetate is used for treating vitamin A deficiency, and the vitamin is fat soluble, is an essential factor for regulating the growth and health of epithelial tissue cells, thins the surface of rough and aged skin, promotes the normalization of cell metabolism, and has obvious wrinkle removing effect. At present, vitamin A acetate is widely applied to industries such as medicines, food additives, feed additives, cosmetics and the like, and the preparation and synthesis of the vitamin A acetate are always concerned.
At present, two technical routes are mainly adopted for industrially synthesizing the vitamin A acetic acid vinegar. One is the C14+ C6 route:
Figure BDA0002805668110000011
and a second route: c15+ C5 route
Figure BDA0002805668110000021
The two routes have defects, more than 50 raw materials are needed in the C14+ C6 route, the reaction steps are long, the fixed investment is large, the intermittent series reaction is adopted, the production control is not easy, in addition, the safety problem exists in the production of the double Grignard reagent, and the safety risk is large during the industrial amplification. The price of triphenylphosphine used as a raw material in a C15+ C5 route is high, and a large amount of triphenylphosphine oxide as a reaction byproduct is solid waste and difficult to treat; in addition, VA produced by the route contains a large amount of cis-isomer, so that the utilization value is reduced.
Patent CN110143874A reports that strong base is used for catalyzing beta-ionone to react with 2-chloropropionate, then selective hydrogenation is carried out to obtain VA, triphenylphosphine oxide is well avoided, strong base is used in the reaction process, a side reaction of condensation of raw materials exists, reaction selectivity is poor, and cost is high.
In order to overcome the defects of the existing production process, a new process with high yield and cost advantage needs to be found.
Disclosure of Invention
The invention aims to provide a preparation method of vitamin A acetate, aiming at the defects in the prior art, and the preparation method has the advantages of high yield, economy, environmental protection and the like.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
a preparation method of vitamin A acetate comprises the following steps:
1) Bromoethanol reacts with acetone to produce a ketal compound of formula i:
Figure BDA0002805668110000031
2) The ketal compound shown in the formula I, five-carbon aldehyde (4-acetoxyl-2-methyl-2-butenal) shown in the formula II and magnesium powder are subjected to in-situ Grignard reaction, and then subjected to acidolysis reaction to generate heptacarbon alcohol shown in the formula III:
Figure BDA0002805668110000032
3) Reacting heptacarbon alcohol shown in a formula III with triphenyl phosphine and hydrochloric acid to generate heptacarbon phosphine salt shown in a formula IV:
Figure BDA0002805668110000033
4) The hepta-phosphine salt shown in the formula IV and beta-ionone are subjected to a Wittig reaction to obtain vitamin A acetate:
Figure BDA0002805668110000034
in step 1) of the present invention, the molar ratio of bromoethanol to acetone is 2 to 10, preferably 3 to 5.
In step 1) of the invention, the reaction is carried out under the action of an acid catalyst, wherein the acid catalyst is one or more selected from concentrated sulfuric acid, hydrogen chloride, methanesulfonic acid, p-toluenesulfonic acid and the like, and preferably more than 98wt% of concentrated sulfuric acid and/or p-toluenesulfonic acid;
preferably, the acid catalyst is used in an amount of 0.1 to 1% by mole based on the acetone.
In the step 1) of the invention, the reaction temperature is-20-60 ℃, preferably 30-50 ℃, and the reaction time is 2-10h.
In the step 1), after the reaction is finished, conventional post-treatment processes such as separation and purification are also included, and the purification is preferably carried out by adopting a rectification method, wherein the preferred rectification conditions are that the rectification temperature is 50-120 ℃, and the pressure is 2-20KPaA.
In step 2) of the present invention, the molar ratio of the ketal compound represented by formula i to the pentanal (4-acetoxy-2-methyl-2-butenal) represented by formula ii is 1.8-2.2, preferably 1.9-2.1:1.9-2.1;
the ketal compound shown in the formula I and the pentanal shown in the formula II can be simultaneously dripped into a reaction system, or the pentanal is firstly added for laying, and then the ketal compound is dripped; preferably, a method of firstly adding penta-carbon aldehyde to lay a foundation and then dripping ketal compounds is adopted; the dripping time of the ketal compound and the pentanal is preferably 1 to 5 hours, and the dripping time of the raw materials is not included in the Grignard reaction time.
In step 2) of the present invention, the grignard reaction is preferably performed in a solvent environment, and the solvent is selected from one or more of tetrahydrofuran, toluene and anhydrous diethyl ether, and is preferably tetrahydrofuran;
preferably, the solvent is used in an amount of 0.5 to 5 times the amount of the ketal compound and is added to the system simultaneously with the ketal compound.
In the step 2), the temperature of the Grignard reaction is 20-80 ℃, and the preferable temperature is 40-60 ℃; the time is 2-10h, preferably 3-5h.
In the step 2) of the invention, the acidolysis reaction is carried out by adding the reaction solution into the acid solution for reaction after the completion of the in-situ Grignard reaction, preferably by continuous feeding such as dropwise addition, wherein the feeding time is 0.5-5h, and the raw material dropwise addition time is included in the acidolysis reaction time.
In the step 2), the acid hydrolysis reaction adopts one or more acids selected from sulfuric acid, hydrochloric acid and phosphoric acid;
the acid is preferably an acid aqueous solution with the concentration of 15-25 wt%;
preferably, the amount of the acid used is 1 to 10 times, preferably 5 to 8 times, the amount of the substance of the ketal compound.
In the step 2), the acidolysis reaction is carried out at the temperature of 15-35 ℃, preferably at the temperature of 20-25 ℃ for 0.5-5h;
after the acidolysis reaction is finished, the conventional post-treatment modes such as liquid separation, water washing, solvent removal under reduced pressure and the like are also included, and the specific method has no special requirement.
In step 3) of the present invention, the molar ratio of the heptanol represented by formula iii to triphenylphosphine and hydrochloric acid (calculated as HCl) is 1:1-1.2:1-1.2;
preferably, the hydrochloric acid concentration is 33 to 36wt%; the hydrochloric acid is preferably fed continuously, such as dropwise, for 1-4h, and the dropwise feeding time of the raw materials is not included in the reaction time.
In step 3) of the present invention, the reaction is preferably performed in a solvent environment, and the solvent is selected from one or more of methanol, ethanol, isopropanol and the like, preferably methanol;
preferably, the amount of the solvent is 2 to 10 times, preferably 4 to 6 times, the mass of the heptanol.
In the step 3), the reaction is carried out at the temperature of 30-70 ℃, preferably at the temperature of 40-60 ℃ for 2-8 hours, preferably for 3-5 hours;
after the reaction is finished, the post-treatment processes of solvent removal, pulping and the like are also included, the preferable method is pulping purification after solvent removal, in some examples, the pulping purification adopts a method of adding n-hexane, keeping the temperature at 60-65 ℃, stirring for 1-2h, and then carrying out suction filtration.
In step 4) of the present invention, the molar ratio of the heptacarbochosphine salt represented by formula IV to the beta-ionone is 0.9-1.1, preferably 1.0-1.05.
In the step 4), the Wittig reaction is carried out under an alkaline condition, wherein the alkali is one or more selected from sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, and preferably sodium carbonate and/or potassium carbonate;
the alkali is preferably alkali aqueous solution with the concentration of 8-15 wt%;
preferably, the molar ratio of the base to the heptaphosphine salt is from 0.5 to 5, preferably from 1 to 2.
In the step 4), the Wittig reaction is carried out at the temperature of 30-70 ℃, preferably at the temperature of 40-60 ℃ for 2-8 hours, preferably for 3-5 hours;
after the Wittig reaction is finished, the method further comprises the conventional treatment modes of extraction liquid separation, water washing, solvent removal and the like, wherein the extraction liquid separation is carried out, and the extraction liquid is selected from normal hexane, normal heptane and the like.
Compared with the prior art, the invention has the advantages that:
the invention provides a brand new synthesis route of C13+ C7 vitamin A acetate, the yield of the vitamin A acetate is improved to 90% (calculated by beta-ionone), the yield is improved by 5-10% compared with the prior art, the content of all-trans VA reaches more than 85%, convenience is provided for subsequent separation and purification, and the method has the advantages of high yield, economy, environmental protection and the like, and is more favorable for industrial production.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
Some of the reagent specifications and sources in the examples and comparative examples:
1. beta-ionone: more than 99 percent, and carbofuran;
2. bromine ethanol: greater than 98%, alatin;
3. aldehyde five carbon: 4-acetoxy-2-methyl-2-butenal was prepared with a purity of > 99% by the method of example 1 of patent CN 1087076A.
Other raw materials are commercially available common reagents unless otherwise specified.
Gas Chromatography (GC): model Agilent WAX 1701.42249; the carrier gas is high-purity nitrogen; the sample injection mode is an automatic sample injector; the nitrogen flow is 64.5ml/min; the temperature of the vaporization chamber is 280 ℃; split-flow sample injection is carried out, and the split-flow ratio is 1; the sample injection amount is 0.2 mul; the column flow rate was 1.5ml/min; the column temperature is first-order temperature programming, the initial temperature is 100 ℃, the temperature is kept for 2 minutes, then the temperature is raised to 230 ℃ at the speed of 15 ℃/min, and the temperature is kept for 15 minutes; the total running time is 25.67min; the temperature of the detector is 300 ℃; and (4) selecting an external standard method for quantification for quantitative analysis.
High Performance Liquid Chromatography (HPLC): shimadzu LC-20A, with SIL-20A autosampler, CTO-10ASvp column oven, SPD-M20A detector, or an instrument with the same performance. Liquid chromatography conditions: the sample injection amount is 1 mu L, the UV detection wavelength is 328nm, and the column oven: 40 ℃, flow rate: 0.4ml/min. And (4) selecting an external standard method for quantification for quantitative analysis.
Nuclear magnetic analysis (NMR): model Bruke Fourier 300, with CDCl3 as solvent, was qualitatively analyzed by 1H NMR.
Example 1
Adding 1249g (10 mol) of bromoethanol and 290g (5 mol) of acetone into a 3L three-necked bottle, heating to 40 ℃, adding 1g (0.01 mol) of concentrated sulfuric acid, carrying out heat preservation reaction for 6h, wherein the conversion per pass of the acetone is 26%, rectifying and separating the reaction solution, the temperature is 80 ℃, the pressure is 10KPaA, the number of tower plates is =50, and the reflux ratio is 10: 316.5g (1.1 mol) of ketal compound are obtained with a GC purity of 99.8%. The ketal compounds were characterized by nuclear magnetic analysis, 1H NMR (300mhz, cdcl3): δ =3.96 (t, JH-H =6.3hz, 4H), 3.69 (t, JH-H =6.3hz, 4H), 1.25 (s, 6H).
Adding 298.2g (2.1 mol) of pentanal, 500g of tetrahydrofuran and 49.9g (2.08 mol) of magnesium powder into a 3L three-necked flask, heating to 60 ℃, slowly dropwise adding a mixed solution of 289.9g (1 mol) of ketal compound and 300g of tetrahydrofuran into the three-necked flask, wherein the dropwise adding time is 4 hours, the reaction temperature in the dropwise adding process is not more than 65 ℃, continuously reacting for 3 hours at 65 ℃ after the dropwise adding is finished, slowly adding the reaction solution into a 5L three-necked flask filled with 2000g of 20wt% hydrochloric acid, completely dropwise adding the reaction solution for 2 hours, stirring at 20 ℃ for 1 hour under heat preservation after the dropwise adding is finished, separating, washing twice by using organic phase water, and removing the solvent to obtain 330g of heptanal, wherein the GC purity is 98%, and the yield is 95.1%. Heptanol was characterized by nuclear magnetic analysis, 1H NMR (300mhz, dmso): δ =5.89-6.11 (m, 3H), 4.62 (d, 2H), 4.21 (d, 2H), 3.88 (S, 1H, hydroxyhydrogen), 2.32 (S, 3H), 2.16 (S, 3H).
Weighing 170g (1 mol) of heptacarbonate, 288.2g (1.1 mol) of triphenylphosphine and 1000g of methanol in a 3L three-necked bottle, heating to 50 ℃, clarifying the system, then slowly adding 105g (1 mol) of 35% concentrated hydrochloric acid into the system, completely dripping for 2h, continuing to perform heat preservation reaction for 2h after the dripping is complete, removing the methanol, adding 1000g of n-hexane into a reaction bottle, stirring for 2h at 60 ℃, performing suction filtration to obtain 406.8g of heptacarbonate, and performing HPLC (high performance liquid chromatography) content: 99.6% and yield 90.2%. Heptac phosphine salt was characterized by nuclear magnetic analysis, 1H NMR (300MHz, DMSO): δ =7.31-7.81 (m, 15H), 5.22-5.36 (m, 5H), 2.36-2.46 (m, 5H), 2.26 (S, 3H).
405.8g (0.9 mol) of heptaphosphine salt, 192g (1 mol) of beta-ionone and 2000g of 10wt% (1.88 mol) of sodium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 60 ℃, kept warm and stirred for 5 hours, 1000g of n-hexane is added into reaction liquid, liquid separation is carried out, organic phase is washed twice, and then the n-hexane is removed to obtain 331g of crude vitamin A acetate oil. Liquid phase analysis was performed to obtain 89% vitamin a acetate (all-trans VA 88%) in 89.8% yield.
Example 2
2498g (20 mol) of bromoethanol and 290g (5 mol) of acetone are added into a 3L three-necked bottle, the temperature is raised to 50 ℃, 0.86g (0.005 mol) of p-toluenesulfonic acid is added, the reaction is kept for 4 hours, the conversion per pass of the acetone is 36%, the reaction liquid is rectified and separated, the temperature is 120 ℃, the pressure is 15KPaA, the number of plates is =50, and the reflux ratio is 10:1, 434.8g (1.5 mol) of ketal compound 1 was obtained with a GC purity of 99.8%.
Adding 269.8g (1.9 mol) of pentanal, 500g of tetrahydrofuran and 45.5g (1.9 mol) of magnesium chips into a 3L three-mouth bottle, heating to 50 ℃, slowly dropwise adding a mixed solution of 289.9g (1 mol) of ketal compound and 300g of tetrahydrofuran into the three-mouth bottle, wherein the dropwise adding time is 5 hours, the reaction temperature in the dropwise adding process is not more than 65 ℃, continuously reacting for 2 hours at 60 ℃ after the dropwise adding is completed, slowly adding the reaction solution into the 5L three-mouth bottle filled with 2000g of 15wt% sulfuric acid, completely dropwise adding for 2 hours, keeping the temperature and stirring for 1 hour at 25 ℃ after the dropwise adding is completed, separating, washing the organic phase twice with water, and removing the solvent to obtain 320g of heptanal, wherein the GC purity is 98%, and the yield is 92.2%.
Weighing 170g (1 mol) of heptacarbonate, 275.1g (1.05 mol) of triphenylphosphine and 1000g of methanol in a 3L three-necked bottle, heating to 50 ℃, clarifying the system, then slowly adding 120g (1.08 mol) of 33% concentrated hydrochloric acid into the system, completely dripping for about 1h, continuing to perform heat preservation reaction for 5h after the dripping is complete, removing the methanol, adding 1000g of n-hexane into a reaction bottle, stirring for 2h at 60 ℃, and performing suction filtration to obtain 406.8g of heptacarbonate, wherein the HPLC content: 99.6% and yield 90.2%.
472.5g (1.05 mol) of heptachlorophosphine, 192g (1 mol) of beta-ionone and 700g of 10wt% (0.5 mol) potassium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 60 ℃, kept warm and stirred for 5 hours, 1000g of n-hexane is added into the reaction solution, liquid separation is carried out, the organic phase is washed twice by water, and then the n-hexane is removed to obtain 336g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 86% (all-trans VA content of 90%) and a yield of 88.1%.
Example 3
Adding 6245g (50 mol) of bromoethanol and 290g (5 mol) of acetone into a 3L three-necked bottle, heating to 50 ℃, adding 1.72g (0.01 mol) of p-toluenesulfonic acid, carrying out heat preservation reaction for 4h, carrying out rectification separation on the reaction solution, wherein the temperature is 50 ℃, the pressure is 2KPaA, the number of plates is =50, and the reflux ratio is 10:1, 463.8g (1.6 mol) of ketal compound are obtained with a GC purity of 99.7%.
Adding 255.6g (1.8 mol) of pentanal, 1000g of tetrahydrofuran and 43.2g (1.8 mol) of magnesium chips into a 3L three-necked flask, heating to 40 ℃, slowly dropwise adding a mixed solution of 289.9g (1 mol) of ketal compound and 300g of tetrahydrofuran into the three-necked flask, wherein the dropwise adding time is 2 hours, the reaction temperature in the dropwise adding process is not more than 65 ℃, continuously reacting for 5 hours at 50 ℃ after the dropwise adding is completed, slowly adding the reaction solution into a 5L three-necked flask filled with 2000g of 25wt% hydrochloric acid, completely dropwise adding for 2 hours, stirring at the constant temperature of 25 ℃ for 1 hour after the dropwise adding is completed, separating, washing twice by using organic phase water, and removing the solvent to obtain 330g of heptanal, wherein the GC purity is 98%, and the yield is 95.1%.
Weighing 170g (1 mol) of heptacarbonate, 314.1g (1.2 mol) of triphenylphosphine and 1700g of methanol in a 3L three-necked bottle, heating to 70 ℃, clarifying the system, slowly adding 120g (1.18 mol) of 36% concentrated hydrochloric acid into the system, completely dripping for about 2h, continuing to perform heat preservation reaction for 3h after the dripping is complete, removing methanol, adding 1000g of n-hexane into a reaction bottle, stirring for 2h at 60 ℃, and performing suction filtration to obtain 419.8g of heptacarbonate, wherein the HPLC content: 99.6% and a yield of 93.1%.
473.4g (1.05 mol) of heptaphosphine salt, 192g (1 mol) of beta-ionone and 2760g of 10wt% (2 mol) potassium carbonate aqueous solution are weighed in a 3L three-necked bottle, heated to 40 ℃, kept warm and stirred for 8 hours, 1000g of n-hexane is added into reaction liquid, liquid separation is carried out, organic phase is washed twice, and then the n-hexane is removed to obtain 346g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 89% (89% all-trans VA content), yield 93.8%.
Comparative example 1
Adding 1.2L vinyl magnesium chloride tetrahydrofuran solution (2 mol/L,2.4 mol) into a 4L three-necked flask, stirring, cooling to 0 ℃, and dropwise adding 401g beta-ionone (2 mol) at a temperature of not more than 10 ℃. After the dropwise addition, the reaction is continued for 2 hours at the temperature of 5-10 ℃. After the reaction, 1L of toluene was added to the three-necked flask, and the tetrahydrofuran was replaced by rectification under reduced pressure. After the replacement, the toluene solution was cooled to 10 ℃ and 1L of water was added, the temperature being controlled not to exceed 20 ℃. After the addition, the stirring is stopped, and the phase separation is carried out by standing. And removing the organic phase by using a solvent to obtain a crude product of the vinyl ionol. The crude product was distilled at 200Pa (absolute pressure) at 130 ℃ to give 422g of vinyl ionol product, 94% content and 90% yield.
288g of triphenylphosphine (1.1 mol) and 2L of methanol were added to a 4L three-necked flask, 118g of hydrochloric acid (37%, 1.2 mol) were added dropwise with stirring, and after the dropwise addition, the temperature was raised to 50 ℃. 234g of vinyl ionol (1.0 mol) were added dropwise to a three-necked flask, and after completion of the addition, the reaction was maintained at 50 ℃ for 2 hours. After the reaction, the reaction solution is brought to 0 ℃, 153g of pentanal (1.0 mol) is added, the mixture is stirred uniformly, 300ml of prepared sodium methoxide methanol solution (5 mol/L,1.5 mol) is added dropwise, and the temperature is controlled not to exceed 5 ℃. After the dropwise addition, the temperature is kept between 0 and 5 ℃ for reaction for 1 hour. After the reaction, the reaction solution was transferred to an extraction vessel and extracted with 3X 1.5L of n-hexane, and the extracts were combined and the solvent was removed to obtain 308g of crude vitamin A acetate oil. Liquid phase analysis was performed with a vitamin a acetate content of 80% (60% all-trans VA content) and a yield of 75%.

Claims (37)

1. A preparation method of vitamin A acetate comprises the following steps:
1) Reacting bromoethanol with acetone to produce a ketal compound of formula I:
Figure FDA0003835531940000011
2) The ketal compound shown in the formula I and the five-carbon aldehyde and magnesium powder shown in the formula II are subjected to in-situ Grignard reaction and then subjected to acidolysis reaction to generate heptacarbon alcohol shown in the formula III:
Figure FDA0003835531940000012
3) Reacting heptacarbon alcohol shown in a formula III with triphenyl phosphine and hydrochloric acid to generate heptacarbon phosphine salt shown in a formula IV:
Figure FDA0003835531940000013
4) The heptacarbon phosphine salt shown in the formula IV and beta-ionone are subjected to a Wittig reaction to obtain vitamin A acetate:
Figure FDA0003835531940000014
2. the method of claim 1, wherein: in the step 1), the molar ratio of the bromoethanol to the acetone is 2-10;
the reaction is carried out under the action of an acid catalyst, and the acid catalyst is one or more selected from concentrated sulfuric acid, hydrogen chloride, methanesulfonic acid and p-toluenesulfonic acid.
3. The method of claim 2, wherein: the molar ratio of the bromoethanol to the acetone is 3-5.
4. The method of claim 2, wherein: the acid catalyst is selected from more than 98wt% of concentrated sulfuric acid and/or p-toluenesulfonic acid.
5. The method of claim 2, wherein: the dosage of the acid catalyst is 0.1-1% of the molar weight of the acetone.
6. The method of claim 1, wherein: in the step 1), the reaction temperature is-20-60 ℃ and the reaction time is 2-10h.
7. The method of claim 6, wherein: the reaction temperature is 30-50 ℃.
8. The method of claim 1, wherein: in the step 2), the molar ratio of the ketal compound shown in the formula I to the pentanal shown in the formula II and the magnesium is 1.8-2.2.
9. The method of claim 8, wherein: the molar ratio of the ketal compound shown in the formula I to the pentanal shown in the formula II is 1.8-2.2.
10. The method of claim 9, wherein: the mol ratio of the ketal compound shown in the formula I to the pentanal and the magnesium shown in the formula II is 1.9-2.1:1.9-2.1.
11. The method of claim 1, wherein: in the step 2), the ketal compound shown in the formula I and the pentanal shown in the formula II are dripped into a reaction system.
12. The method of claim 11, wherein: the dropping time is 1-5h, and the dropping time of the raw materials is not included in the Grignard reaction time.
13. The method of claim 1, wherein: in the step 2), the Grignard reaction is carried out in a solvent environment, and the solvent is selected from one or more of tetrahydrofuran, toluene and anhydrous ether;
the Grignard reaction is carried out at the temperature of 20-80 ℃ for 2-10h.
14. The method of claim 13, wherein: the dosage of the solvent is 0.5 to 5 times of the mass of the ketal compound.
15. The method of claim 13, wherein: the Grignard reaction is carried out at the temperature of 40-60 ℃ for 3-5h.
16. The method of claim 1, wherein: in the step 2), the acidolysis reaction is to add the reaction solution into the acid solution for reaction after the in-situ Grignard reaction is finished;
the acidolysis reaction adopts one or more acids selected from sulfuric acid, hydrochloric acid and phosphoric acid;
the acidolysis reaction is carried out at the temperature of 15-35 ℃ for 0.5-5h.
17. The method of claim 16, wherein: adding the reaction solution into the acid solution, and adopting a continuous feeding mode, wherein the feeding time is 0.5-5h, and the dropping time of the raw materials is contained in the acidolysis reaction time.
18. The method of claim 16, wherein: the acid hydrolysis reaction adopts acid selected from 15-25wt% acid water solution.
19. The method of claim 16, wherein: the dosage of the acid is 1 to 10 times of the mass of the ketal compound.
20. The method of claim 19, wherein: the amount of the acid is 5-8 times of the mass of the ketal compound.
21. The method of claim 16, wherein: the acidolysis reaction is carried out at the temperature of 20-25 ℃.
22. The method of claim 1, wherein: in the step 3), the molar ratio of the heptanol shown in the formula III to the triphenyl phosphine and the hydrochloric acid is 1:1-1.2:1-1.2;
the reaction is carried out in a solvent environment, and the solvent is selected from one or more of methanol, ethanol and isopropanol.
23. The method of claim 22, wherein: the concentration of the hydrochloric acid is 33-36wt%.
24. The method of claim 22, wherein: the hydrochloric acid adopts a continuous feeding mode.
25. The method of claim 24, wherein: the hydrochloric acid is added dropwise in a manner that the feeding time is 1-4h, and the dropwise adding time of the raw materials is not included in the reaction time.
26. The method of claim 22, wherein: the dosage of the solvent is 2-10 times of the mass of the heptacarbon alcohol.
27. The method of claim 26, wherein: the dosage of the solvent is 4-6 times of the mass of the heptacarbon alcohol.
28. The method of claim 1, wherein: in the step 3), the reaction is carried out at the temperature of 30-70 ℃ for 2-8h.
29. The method of claim 28, wherein: the reaction is carried out at the temperature of 40-60 ℃ for 3-5h.
30. The method of claim 1, wherein: in the step 4), the mole ratio of the heptacarbochosphine salt shown in the formula IV to the beta-ionone is 0.9-1.1;
the Wittig reaction is carried out under an alkaline condition, and the alkali is one or more selected from sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
31. The method of claim 30, wherein: the molar ratio of the hepta-phosphine salt to the beta-ionone shown in the formula IV is 1.0-1.05.
32. The method of claim 30, wherein: the alkali is selected from sodium carbonate and/or potassium carbonate.
33. The method of claim 30, wherein: the alkali adopts alkali water solution with the concentration of 8-15 wt%.
34. The method of claim 30, wherein: the molar ratio of the base to the heptacarbochosphine salt is 0.5-5.
35. The method of claim 30, wherein: the molar ratio of the base to the heptaphosphine salt is 1-2.
36. The method of claim 1, wherein: in the step 4), the Wittig reaction is carried out at the temperature of 30-70 ℃ for 2-8h.
37. The method of claim 36, wherein: the Wittig reaction is carried out at the temperature of 40-60 ℃ for 3-5h.
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