CN110903190B - Preparation method of vitamin A and vitamin A ester - Google Patents
Preparation method of vitamin A and vitamin A ester Download PDFInfo
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- CN110903190B CN110903190B CN201911254673.9A CN201911254673A CN110903190B CN 110903190 B CN110903190 B CN 110903190B CN 201911254673 A CN201911254673 A CN 201911254673A CN 110903190 B CN110903190 B CN 110903190B
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- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
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- C07C29/40—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing carbon-to-metal bonds
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- 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
- C07C403/08—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 hydroxy groups
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- 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
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Abstract
The invention provides a novel method for preparing vitamin A and vitamin A ester by taking farnesene as a raw material. Comprises the following steps: reacting farnesene with acetoacetate under the action of a catalyst to obtain farnesyl ketonate; carrying out cyclization reaction and dehydrogenation reaction on farnesene acetone, and then reacting with vinyl magnesium halide to generate vinyl alcohol; carrying out rearrangement reaction on vinyl alcohol to obtain vitamin A; the vitamin A is esterified to obtain the vitamin A ester. The method avoids the defects of the prior art, and the process line is economical and effective.
Description
Technical Field
The invention belongs to the field of fine chemical synthesis, and particularly relates to a method for preparing vitamin A and vitamin A ester.
Background
Vitamin A acetate is an important nutritional chemical, has effects of promoting growth and development of human body, and enhancing disease resistance. Meanwhile, the vitamin A acetate is also an important feed additive and has various physiological functions of promoting the synthesis of animal immunoglobulin, promoting growth and reproduction and the like.
At present, two technical routes are mainly adopted for industrially synthesizing the vitamin A ester.
One is C14+ C6 route
The other is a C15+ C5 route
The two routes have defects respectively, the C14+ C6 routes require more than 50 raw materials, have long reaction steps and large fixed investment, are in series reaction and are not easy to control production. VA generated by the C15+ C5 route contains a large amount of cis-isomers, so that the utilization value is reduced. The two routes both use the same initial raw material citral, and at present, citral is only produced by BASF, Colorado and other large companies, and the raw material source is limited, so that the production of vitamin A is restricted.
Patent CN1330621A discloses a process for producing vitamin a ester using farnesyl group compound farnesol produced by biological method as raw material, in which farnesol is subjected to multi-step reaction to produce vitamin a and its ester. The route has long steps, uses various special reagents and is not beneficial to industrial production.
In order to overcome the defects of the existing production processes, a new economic and environment-friendly process needs to be found.
Disclosure of Invention
The invention aims to provide an economic and environment-friendly novel process for synthesizing vitamin A and vitamin A ester, which has the characteristics of high yield, economy and environment friendliness.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for preparing vitamin A and vitamin A ester comprises the following steps:
(1) farnesene reacts with acetoacetate to obtain farnesyl ketoester, and the farnesene acetone is obtained by continuous hydrolysis and decarboxylation;
(2) carrying out cyclization reaction and dehydrogenation reaction on farnesene acetone, and then reacting with vinyl magnesium halide to generate vinyl alcohol;
(3) carrying out rearrangement reaction on vinyl alcohol to obtain vitamin A;
(4) the vitamin A is esterified to obtain the vitamin A ester.
The reaction equation is:
farnesene acetone, if directly dehydrogenated, would produce excessive dehydrogenation by-products, reducing the reaction yield, and making separation difficult. The farnesene acetone is firstly cyclized to generate the ketone I and then is subjected to dehydrogenation reaction, so that excessive dehydrogenation side reaction is avoided, the reaction yield is improved, and the separation difficulty is reduced.
The compounds from ketone II to vitamin A are unstable, and are prone to side reactions such as isomerization, rearrangement, dehydration, and the like, especially at high temperatures. By adopting the Grignard reaction and catalytic rearrangement reaction process, on one hand, the process conditions are mild, the reaction temperature is low, the Grignard reaction temperature is less than or equal to 20 ℃, the rearrangement reaction temperature is 30-50 ℃, and the probability of side reaction is reduced; on the other hand, the Grignard reaction and the rearrangement reaction have high selectivity, and the product does not need to be subjected to a high-temperature rectification separation process, so that the occurrence of side reactions is further reduced. Due to the superposition of the two factors, the production control of the vitamin A is simple, the yield is high, and the industrialization is easier to realize.
In the present invention, a catalyst is added in the reaction of step (1) to produce the farnesyl ketonate, the catalyst is a rhodium-containing compound, preferably the rhodium-containing compound is one or more of (acetylacetonato) dicarbonylrhodium, bis (1, 5-cyclooctadiene) rhodium chloride, rhodium acetate, rhodium octanoate, dicarbonylrhodium chloride, rhodium acetylacetonate, acetylacetonato triphenylphosphine rhodium carbonyl and tris (triphenylphosphine) rhodium chloride, more preferably bis (1, 5-cyclooctadiene) rhodium chloride.
In the invention, the dosage of the catalyst for the reaction of generating the farnesyl ketoester in the step (1) is 0.01-0.1 percent of the mass of the farnesene.
In the invention, an auxiliary agent is added in the reaction of generating the farnesyl ketonic acid ester in the step (1), and the auxiliary agent is triphenylphosphine.
In the invention, the dosage of the auxiliary agent for the reaction of generating the farnesoid ester in the step (1) is 1-5% of the mass of the farnesene.
In the present invention, the acetoacetate in step (1) is methyl acetoacetate and/or ethyl acetoacetate.
In the invention, the usage amount of the acetoacetate ester in the reaction of generating the farnesyl ketoester in the step (1) is 1.2-1.52 times of the molar weight of the farnesene.
In the present invention, the reaction of step (1) to produce farnesyl ketonate is carried out in a solvent selected from one or more of alkanes, cycloalkanes, aromatic hydrocarbons, alcohols, ethers, esters, amides and chloroalkanes, preferably ethanol.
In the invention, the reaction temperature for generating the farnesyl ketonate in the step (1) is 50-80 ℃.
In the invention, a catalyst is added in the hydrolysis and decarboxylation reaction in the step (1), and the catalyst is an alkaline catalyst, preferably sodium hydroxide.
In the invention, the dosage of the catalyst for the hydrolysis and decarboxylation reaction in the step (1) is 0.1-1% of the mass of the farnesyl ketonate.
In the invention, the temperature of the hydrolysis and decarboxylation reaction in the step (1) is 80-100 ℃.
In the invention, the ring-closure reaction in the step (2) is carried out to obtain the ketone I.
In the invention, a catalyst is added in the cyclization reaction in the step (2), and the catalyst is one or more of sulfuric acid, phosphoric acid and trifluoromethanesulfonic acid.
In the invention, the dosage of the cyclization reaction catalyst in the step (2) is 0.5-2 times of the mass of farnesene acetone.
In the present invention, the cyclization reaction of step (2) is carried out in a solvent selected from one or more of alkanes, cycloalkanes, aromatic hydrocarbons, ethers, esters, amides and chloroalkanes, preferably dichloroethane.
In the invention, ketone I in step (2) is subjected to dehydrogenation reaction to generate ketone II.
In the invention, the dehydrogenation reagent in the step (2) is DDQ (dichlorodicyanoquinone) and/or tetrachloro-p-benzoquinone.
In the invention, the dosage of the dehydrogenation reagent in the step (2) is 1.04-1.2 times of the molar weight of the ketone I.
In the present invention, the dehydrogenation reaction of step (2) is carried out in a solvent selected from one or more of alkanes, cycloalkanes, aromatics, ethers, esters, amides and chloroalkanes, preferably toluene.
In the invention, the temperature of the dehydrogenation reaction in the step (2) is 30-50 ℃.
In the invention, the time of dehydrogenation reaction in the step (2) is 0.5-2 h.
In the present invention, the vinyl magnesium halide in the step (2) is selected from vinyl magnesium chloride and/or vinyl magnesium bromide.
In the invention, the dosage of the vinyl magnesium halide in the step (2) is 1.05-1.2 times of the molar equivalent of the ketone II.
In the present invention, the reaction temperature for forming the vinyl alcohol in the step (2) is 0 to 20 ℃.
In the present invention, the rearrangement reaction in step (3) is carried out under the catalysis of HCl.
In the invention, the dosage of HCl in the step (3) is 1-5% of the mass of the vinyl alcohol.
In the present invention, the rearrangement reaction in step (3) is carried out in a solvent selected from one or more of alkanes, cycloalkanes, aromatics, ethers, esters, amides, and chloroalkanes, preferably toluene.
In the present invention, the temperature of the rearrangement reaction in the step (3) is 30 to 50 ℃.
In the present invention, the acid of the esterification reaction in step (3) is one or more of carboxylic acid, anhydride and acyl chloride, preferably acetic anhydride and/or palmitoyl chloride.
In the invention, the amount of the acid used in the esterification reaction in the step (3) is 1-1.1 times of the molar amount of the vitamin A.
In the present invention, the esterification reaction in step (3) is carried out in a solvent selected from one or more of alkanes, cycloalkanes, aromatic hydrocarbons, ethers, esters, amides, chloroalkanes, preferably hexane.
It is another object of the present invention to provide a vitamin a and/or a vitamin a ester.
Vitamin A and/or vitamin A ester are prepared by the preparation method of the vitamin A and the vitamin A ester.
Compared with the existing synthetic route of vitamin A and the ester thereof, the method of the invention has the following positive effects:
a. the reaction steps are few, the yield is high, and the yield of the vitamin A ester is more than 69 percent based on farnesene;
b. the reaction conditions of the steps are mild, and the industrial production is easy to realize;
c. avoids the generation of three wastes which are difficult to treat, and is green and environment-friendly.
Detailed Description
The process of the present invention is further illustrated by the following specific examples, but the invention is not limited to the examples set out above, but also encompasses any other known modification within the scope of the claims of the present invention.
Main reagent specifications and sources
| Name of reagent | Reagent specification | Manufacturer of the product |
| Farnesene | ＞95％ | Bailingwei-medicine |
| Acetoacetic acid methyl ester | ＞98％ | Bailingwei-medicine |
| Acetoacetic acid ethyl ester | ＞98％ | Bailingwei-medicine |
| Vinyl magnesium bromide solution | 2mol/L | Bailingwei-medicine |
| Vinyl magnesium chloride solution | 2mol/L | Bailingwei-medicine for curing cancer |
| DDQ | ＞99％ | Bailingwei-medicine |
| Tetrachloro p-benzoquinone | ＞99％ | Bailingwei-medicine |
| Acetic anhydride | ＞99％ | Bailingwei-medicine |
| Palmitoyl chloride | ＞98％ | Bailingwei-medicine |
| Citral | ＞97％ | Bailingwei-medicine for curing cancer |
| Triphenylphosphine | ＞99％ | Bailingwei-medicine |
| Five carbon aldehyde | ＞96％ | Self-production |
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 64.5 ml/min; the temperature of the vaporization chamber is 280 ℃; split-flow sample injection is carried out, and the split-flow ratio is 1: 40; the sample injection amount is 0.2 mul; the column flow rate was 1.5 ml/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 25.67 min; the temperature of the detector is 300 ℃; an external standard method is selected for quantification and is used for quantitatively analyzing farnesyl ketonate, farnesene acetone, ketone I, ketone II and vinyl alcohol.
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: 0.4 ml/min. The external standard method is adopted for quantitative analysis of vitamin A and vitamin A ester.
Nuclear magnetic analysis (NMR): model Bruke Fourier 300 in CDCl3As a solvent, by1H NMR qualitative analysis of farnesene acetone, ketone I, vinyl alcohol.
Example 1
1075g of farnesene, 800g of ethyl acetoacetate, 5L of ethanol, 0.11g of bis (1, 5-cyclooctadiene) rhodium chloride and 11g of triphenylphosphine were added to the reactor and stirred. The reaction was stopped after 24 hours at 50 ℃. Distilling to remove the solvent and light components, and then carrying out reduced pressure distillation to obtain 1586g of ethyl farnesonate with the content of 95% and the yield of 94%.
1500g of ethyl farnesoate and 150g of 1% sodium hydroxide solution were added to the reactor and stirred. Reacting at 100 ℃ for 5h, and cooling to room temperature. The phases are separated and the organic phase is neutralized to neutrality using acetic acid. Distilling to remove the solvent and light components, and then carrying out vacuum rectification to obtain 1181g of farnesene acetone, wherein the content is 98%, and the yield is 96%.1H NMR(300MHz,CDCl3) The characterization result is as follows: δ is 5.22(m,3H),2.52(m,2H),2.26(m,2H),2.12(s,3H),2.03(m,8H),1.86(m,6H),1.70(m, 6H).
2000g of concentrated sulfuric acid and 2000g of dichloroethane are added to the reactor, stirred and cooled to 0 ℃. A mixture of 1000g of farnesene acetone and 1000g of dichloroethane was added dropwise thereto at such a rate that the temperature of the reaction mixture did not exceed 5 ℃. After the addition, the reaction was quenched with 4000g of water. Phase separation, organic phase distillation to remove solvent, vacuum rectification to obtain 950g of ketone I, content of 98%, yield of 93%. δ -5.16 (m,1H),2.50(dt,2JH-H＝5Hz,3JH-H＝3Hz,2H),2.22(q,2JH-H＝5Hz,2JH-H＝5Hz,2H),2.13(s,3H),1.96(m,6H),1.80(m,8H),1.57(t,2JH-H＝5Hz,2H),1.25(s,6H)。
900g of ketone I, 925g of DDQ and 4L of toluene are added to the reactor and stirred. The temperature is increased to 50 ℃ and the reaction is carried out for 0.5 h. After the reaction, the solvent was removed by distillation, and the reaction was distilled under reduced pressure to obtain 842g of ketone II, the content of which was 98%, and the yield was 95%.
1.8L of vinyl magnesium chloride solution is added into the reactor, stirred and cooled to 20 ℃. 800g of ketone II are added dropwise, and the temperature of the reaction solution does not exceed 20 ℃ in the dropwise addition process. After the dropwise addition, the reaction was maintained at 20 ℃ for 1 h. After the reaction, 300g of water was added to the reaction solution, filtered, and the organic phase was distilled to remove the solvent, to obtain 860g of vinyl alcohol, 96% in content, and 95% in yield. δ is 6.49(m,3H),6.20(m,1H),5.90(m,2H),5.28(m,2H),3.65(br,1H),2.20(m,3H),1.96(t,2JH-H＝5Hz,2H),1.88(s,3H),1.76(m,2H),1.57(t,2JH-H＝5Hz,2H),1.50(s,3H),1.26(s,6H)。
800g of vinyl alcohol and 4L of toluene were added to the reactor, stirred and heated to 50 ℃. 40g of HCl gas was introduced and the reaction was carried out for 1 h. After the reaction is finished, the temperature is reduced to-15 ℃ and kept for 10 h. And (5) filtering. The solid was washed with toluene and dried to give 776g of vitamin A solid with 98% content and 95% yield.
600g of vitamin A and 3L of n-hexane were added to the reactor, 207g of acetic anhydride was added dropwise with stirring, and the temperature was controlled at 35 ℃. After the dropwise addition, the reaction was carried out at 35 ℃ for 1 hour. After the reaction, the light components were removed by distillation under reduced pressure to obtain 690g of vitamin A acetate solid with a content of 97% and a yield of 99.5%.
Example 2
1075g of farnesene, 990g of ethyl acetoacetate, 5L of ethanol, 1.1g of bis (1, 5-cyclooctadiene) rhodium chloride and 54g of triphenylphosphine were charged into the reactor and stirred. The reaction was stopped after 10h at 80 ℃. Distilling to remove the solvent and light components, and then carrying out reduced pressure distillation to obtain 1569g of ethyl farnesonate, the content of which is 95 percent and the yield of which is 93 percent.
1500g of ethyl farnesoate and 1500g of 1% sodium hydroxide solution were added to the reactor and stirred. Reacting at 80 ℃ for 2h, and cooling to room temperature. The phases were separated and the organic phase was neutralized to neutrality with acetic acid. Distilling to remove the solvent and light components, and then carrying out reduced pressure rectification to obtain 1169g of farnesene acetone with the content of 98% and the yield of 95%.
500g of phosphoric acid, 1000g of farnesene acetone and 2000g of toluene were added to the reactor and stirred. The temperature is increased to 50 ℃ and the reaction is carried out for 3 h. After the reaction is finished, cooling to room temperature, standing and phase splitting. After the organic phase is distilled to remove the solvent, the organic phase is rectified under reduced pressure to obtain 940g of ketone I, the content is 98 percent, and the yield is 92 percent.
900g of ketone I, 880g of tetrachlorop-benzoquinone and 4L of tetrahydrofuran were charged into the reactor and stirred. The reaction was maintained at 30 ℃ for 2 h. After the reaction, the solvent was removed by distillation, and 824g of ketone II was obtained by distillation under reduced pressure with a content of 98% and a yield of 93%.
1.6L of vinyl magnesium bromide solution was added to the reactor, stirred and cooled to 0 ℃. 800g of ketone II are added dropwise, and the temperature of the reaction solution does not exceed 0 ℃ in the dropwise addition process. After the dropwise addition, the reaction was carried out for 3 hours while maintaining the temperature at 0 ℃. After the reaction, 300g of water was added to the reaction solution, filtered, and the organic phase was distilled to remove the solvent, to obtain 878g of vinyl alcohol, 96% in content, and 97% in yield.
800g of vinyl alcohol and 4L of toluene were charged into the reactor, stirred, and maintained at 30 ℃. 8g of HCl gas are introduced and the reaction is carried out for 4 hours. After the reaction is finished, the temperature is reduced to-15 ℃ and kept for 10 h. And (4) filtering. The solid was washed with toluene and dried to give 776g of vitamin A solid with 98% content and 95% yield.
600g of vitamin A and 3L of toluene were added to the reactor, and 573g of palmitoyl chloride was added dropwise with stirring, the temperature being controlled at 35 ℃. After the dropwise addition, the reaction was carried out at 35 ℃ for 1 hour. After the reaction, the reaction product is washed by water, and light components are removed, so that 1100g of vitamin A palmitate solid with the content of 97 percent and the yield of 99 percent is obtained.
Example 3
1075g of farnesene, 800g of methyl acetoacetate, 5L of ethanol, 0.5g of bis (1, 5-cyclooctadiene) rhodium chloride and 30g of triphenylphosphine were charged into the reactor and stirred. The reaction was stopped after 15 hours at 70 ℃. Distilling to remove the solvent and light components, and then carrying out reduced pressure distillation to obtain 1569g of methyl farnesonate, the content of which is 95 percent and the yield of which is 93 percent.
1500g of methyl farnesoate and 500g of 1% sodium hydroxide solution were added to the reactor and stirred. Heating to 90 ℃ for reaction for 2h, and cooling to room temperature. The phases are separated and the organic phase is neutralized to neutrality using acetic acid. Distilling to remove the solvent and light components, and then carrying out reduced pressure rectification to obtain 1193g of farnesene acetone with the content of 98% and the yield of 97%.
1000g of trifluoromethanesulfonic acid, 1000g of dehydrofarnesal and 2000g of dichloromethane were added to a reactor, stirred and reacted under reflux for 3 hours. After the reaction is finished, cooling to room temperature, standing and phase splitting. After the organic phase is distilled to remove the solvent, the organic phase is rectified under reduced pressure to obtain 930g of ketone I with the content of 98 percent and the yield of 91 percent.
900g of ketone I, 848g of DDQ and 4L of ethyl acetate were added to the reactor, and the mixture was stirred. The reaction was maintained at 40 ℃ for 1 h. After the reaction, the solvent was removed by distillation, and the reaction was distilled under reduced pressure to obtain 824g of ketone II, the content of which was 98%, and the yield was 93%.
1.7L of vinyl magnesium chloride solution is added into the reactor, stirred and cooled to 10 ℃. 800g of ketone II are added dropwise, and the temperature of the reaction solution does not exceed 10 ℃ during the dropwise addition. After the dropwise addition, the reaction was carried out at 0 ℃ for 1 hour. After the reaction, 300g of water was added to the reaction solution, filtered, and the organic phase was distilled to remove the solvent, to obtain 869g of alcohol I, 96% in content, and 96% in yield.
800g of vinyl alcohol and 4L of toluene were charged into the reactor, stirred and maintained at 40 ℃. 24g of HCl gas was introduced and the reaction was carried out for 4 h. After the reaction is finished, the temperature is reduced to-15 ℃ and kept for 10 h. And (5) filtering. The solid was washed with toluene and dried to give 784g of vitamin A as a solid with a content of 98% and a yield of 96%.
600g of vitamin A, 167g of propionic acid, 1g of p-toluenesulfonic acid and 3L of hexane were added to the reactor, and the mixture was stirred. Heating at 60 ℃, refluxing, dividing water, and reacting for 2 h. After the reaction is finished, washing with water, and removing light components to obtain 720g of vitamin A propionate solid with the content of 96% and the yield of 98%.
Comparative example 1
100g of citral, 1000g of acetone and 40g of 1% aqueous sodium hydroxide solution were mixed, heated to 60 ℃ and reacted for 0.5 h. After the reaction is finished, acetic acid is added to neutralize to be neutral. Vacuum distillation is carried out to remove acetone, then phase separation is carried out, and the organic phase is rectified to obtain the pseudo ionone with the yield of 89%.
1000g of concentrated sulfuric acid and 1000g of dichloromethane are mixed, the temperature is reduced to-10 ℃, and a solution formed by 500g of pseudoionone and 500g of dichloromethane is dripped. After the dropwise addition, the reaction solution is added into 4000g of water, the mixture is kept stand for phase splitting, and the organic phase is washed by alkali and water to be neutral. After the organic phase is distilled to remove the solvent, the beta-ionone is obtained by reduced pressure rectification, and the yield is 80%.
Cooling 400g beta-ionone and 2L tetrahydrofuran to-10 ℃, dropwise adding 1.3L vinyl magnesium chloride solution, after dropwise adding, heating to 20 ℃ and reacting for 2 h. After the reaction was completed, 1000g of a saturated ammonium chloride solution was added to the reaction solution. Extracting with 3 × 1L of toluene, and removing the solvent from the extract to obtain vinyl ionol with a yield of 90%.
Mixing 260g of triphenylphosphine, 100g of concentrated hydrochloric acid and 1000g of methanol, heating to 50 ℃, dropwise adding 220g of vinyl ionol, and keeping the temperature for reacting for 2 hours after the dropwise adding is finished. After the reaction, 150g of pentanal was added to the system. Dropping sodium methoxide methanol solution at 50 deg.c, and maintaining at 50 deg.c for reaction for 2 hr. And after the reaction is finished, adding 1.5L of n-hexane into the system for extraction, and removing the solvent from the extract liquor to obtain a crude product of the vitamin A acetate. After ethanol crystallization, vitamin A acetate crystals are obtained with a yield of 80%. The total yield of the vitamin A acetate is 51 percent based on the citral.
The technical scheme of the invention is to be modified or replaced equivalently without departing from the scope of the technical scheme of the invention, and the technical scheme of the invention is covered by the protection scope of the invention.
Claims (13)
1. A preparation method of vitamin A and vitamin A ester is characterized by comprising the following steps:
(1) the farnesene and the acetoacetate react to obtain farnesyl keto ester, and the farnesene acetone is obtained by continuous hydrolysis and decarboxylation;
(2) carrying out cyclization reaction and dehydrogenation reaction on farnesene acetone, and then reacting with vinyl magnesium halide to generate 3, 7-dimethyl-9- (2,6, 6-trimethyl-1-cyclohexenyl) -1,4,6, 8-nonatetraen-3-ol;
(3)3, 7-dimethyl-9- (2,6, 6-trimethyl-1-cyclohexenyl) -1,4,6, 8-nonatetraen-3-ol is subjected to rearrangement reaction to obtain vitamin A;
(4) the vitamin A is subjected to esterification reaction to obtain the vitamin A ester.
2. The method of claim 1, wherein the step (1) of reacting to produce the farnesyl ester is carried out with the addition of a catalyst comprising a rhodium-containing compound;
and/or the dosage of the catalyst is 0.01-0.1% of the mass of the farnesene;
and/or adding an auxiliary agent in the reaction of generating the farnesyl ketonate in the step (1), wherein the auxiliary agent is triphenylphosphine;
and/or the dosage of the auxiliary agent is 1-5% of the mass of the farnesene.
3. The process of claim 2, wherein the catalyst of step (1) is one or more of rhodium (acetylacetonate) dicarbonyl, bis (1, 5-cyclooctadiene) rhodium chloride, rhodium acetate, rhodium octanoate, rhodium dicarbonyl chloride, rhodium acetylacetonate, triphenylphosphine rhodium carbonyl acetylacetonate, and tris (triphenylphosphine) rhodium chloride.
4. The process of claim 3, wherein the catalyst of step (1) is bis (1, 5-cyclooctadiene) rhodium chloride.
5. The process according to claim 1, wherein the acetoacetate ester of step (1) is methyl acetoacetate and/or ethyl acetoacetate;
and/or the dosage of the acetoacetic ester is 1.2 to 1.52 times of the molar weight of the farnesene;
and/or the reaction temperature for generating the farnesyl ketonic acid ester is 50-80 ℃.
6. The method according to claim 1, wherein in the step (1), a catalyst is added in the hydrolysis and decarboxylation reaction, and the catalyst is a basic catalyst;
and/or the dosage of the catalyst is 0.1-1% of the mass of the farnesyl ketoester.
7. The method of claim 6, wherein the catalyst in step (1) is sodium hydroxide.
8. The process of claim 1, wherein the cyclization in step (2) provides ketone I having the structure:
and/or adding a catalyst in the cyclization reaction, wherein the catalyst is one or more of sulfuric acid, phosphoric acid and trifluoromethanesulfonic acid;
and/or the dosage of the cyclization reaction catalyst is 0.5-2 times of the mass of the farnesene acetone.
9. The process of claim 1, wherein in step (2), ketone I is dehydrogenated under a dehydrogenation reagent to form ketone II having the following structure:
and/or the dehydrogenation reagent is DDQ (2, 3-dichloro-5, 6-dicyanobenzoquinone) and/or tetrachloro-p-benzoquinone;
and/or the dosage of the dehydrogenation reagent is 1.05 to 1.2 times of the molar weight of the ketone I;
and/or the temperature of the dehydrogenation reaction is 30-50 ℃.
10. The process of claim 1, wherein the vinyl magnesium halide in step (2) is vinyl magnesium chloride and/or vinyl magnesium bromide;
and/or the dosage of the vinyl magnesium halide is 1.05 to 1.2 times of the molar equivalent of the ketone II;
and/or the reaction temperature for generating the 3, 7-dimethyl-9- (2,6, 6-trimethyl-1-cyclohexenyl) -1,4,6, 8-nonatetraen-3-ol is 0-20 ℃.
11. The process of claim 1, wherein the rearrangement reaction in step (3) is carried out under catalysis of HCl;
and/or the amount of HCl is 1-5% of the mass of 3, 7-dimethyl-9- (2,6, 6-trimethyl-1-cyclohexenyl) -1,4,6, 8-nonatetraen-3-ol;
and/or the temperature of the rearrangement reaction is 30-50 ℃.
12. The method according to claim 1, wherein the raw material of the esterification reaction in the step (4) is one or more of carboxylic acid, acid anhydride and acid chloride;
and/or the amount of one or more of carboxylic acid, anhydride and acyl chloride in the step (4) is 1-1.1 times of the molar amount of the vitamin A.
13. The method according to claim 1, wherein the raw material for the esterification reaction in the step (4) is acetic anhydride and/or palmitoyl chloride.
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