CN117756688A - Preparation and purification method of apoester - Google Patents

Preparation and purification method of apoester Download PDF

Info

Publication number
CN117756688A
CN117756688A CN202311816539.XA CN202311816539A CN117756688A CN 117756688 A CN117756688 A CN 117756688A CN 202311816539 A CN202311816539 A CN 202311816539A CN 117756688 A CN117756688 A CN 117756688A
Authority
CN
China
Prior art keywords
cobalt
aporate
nickel
solution
crude product
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202311816539.XA
Other languages
Chinese (zh)
Inventor
王嘉辉
栾晓琳
沈宏强
薛爱国
邢坤
罗朝辉
张弈宇
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wanhua Chemical Group Co Ltd
Original Assignee
Wanhua Chemical Group Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wanhua Chemical Group Co Ltd filed Critical Wanhua Chemical Group Co Ltd
Priority to CN202311816539.XA priority Critical patent/CN117756688A/en
Publication of CN117756688A publication Critical patent/CN117756688A/en
Pending legal-status Critical Current

Links

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)

Abstract

The invention provides a preparation and purification method of aporate, which comprises the following steps of 1) preparation: dissolving deca-dialdehyde, C5 phosphine salt and C15 phosphine salt in an organic solvent to serve as reaction raw materials, taking organic alkali liquor as a catalyst, heating, adding a cobalt-nickel type supported catalyst to complete transposition operation, and filtering the reaction solution to obtain a crude product of aporate; 2) Purifying: dissolving the crude product of the aporate in a bi-component organic solvent, heating to dissolve completely, cooling and crystallizing, and filtering the reaction solution to obtain the aporate product. The reaction yield of the apoester product prepared by the process is more than 90%, the purity of the product is more than 99.5%, the content of impurity beta-carotene is less than 0.3%, the content of all-trans is more than 98%, the average grain diameter of crystals is 50-100 um, the crystal forms are uniform, the preparation development is facilitated, and the product can reach international first-class quality.

Description

Preparation and purification method of apoester
Technical Field
The invention belongs to the technical field of preparation of apoester, and particularly relates to a preparation and purification method of apoester.
Background
In the field of food and feed coloration, apoester (beta-apo-8' -ethyl carotene) forms a main functional nutritional colorant with beta-carotene, canthaxanthin and the like, and is used as a chemically synthesized carotenoid which contains 30 unsaturated conjugated carbon chains in two main modes: US5773635, US7547807 report the use of the Wittig and Wittig-Horner processes, i.e. the reaction of β -apo-12' -carotenal containing 25 carbon atoms with (3-ethoxycarbonyl-2-buten-1-yl) triphenylphosphine halogenate or ethyl 4- (diethoxyphosphoryl) -2-methyl-2-butenoate under the action of a base to give apo-esters. The Wittig method can produce triphenylphosphine oxide byproduct after reaction, and the content of triphenylphosphine oxide is required to be less than 200ppm for an aporate product, so that the subsequent purification operation is complicated, and the product loss can be generated; compared with the Wittig method, the Wittig-Horner method can avoid the complicated problem caused by the purification of triphenylphosphine oxide, but because the reaction activity is high, journal beta-carotene is easy to generate, and because the beta-carotene is also a long-chain alkene compound, the purification of the final product is incomplete.
The Wittig and Wittig-Horner method is adopted, because 5-10% of beta-carotene is inevitably produced in the synthesis of aporate, not only is the subsequent separation difficult, but also the quality problem of the product is affected.
The patent CN 114957070A adopts a one-pot method to mix and react C5 phosphate, C15 phosphonate, C10 dialdehyde and a catalyst, and the obtained product is difficult to avoid producing 1% beta-carotene, which can lead to the production of beta-carotene after separation in the final product, reduce the purity of the product, influence the color of the product due to the existence of beta-carotene, cause the difference between the color of the downstream preparation product and the standard product, and influence the selling of the product.
Therefore, new synthesis and purification processes of the apoester still need to be developed, so that the efficient production of the apoester is realized, and the quality of the product is improved.
Disclosure of Invention
Aiming at the problems in the prior art, one of the purposes of the invention is to provide a preparation method of apoester, which effectively reduces cis-configuration in apoester by adopting a supported cobalt-nickel catalyst and improves the crystallization yield of the product.
The second purpose of the invention is to provide a purification method of the crude product of the apoester, which effectively solves the problems of complex product purification operation, lower yield and difficult purification in the prior art.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
the invention provides a preparation method of aporate, which comprises the following steps:
1) Mixing C15 phosphine salt, C5 phosphine salt and a solvent A to prepare a solution A in a nitrogen atmosphere; mixing dodecenal with a solvent B to prepare a solution B;
2) And (3) under the nitrogen atmosphere, adding the solution B and the organic alkali liquor into the solution A, then adding the supported nickel-cobalt bimetallic catalyst for reaction, adding the solvent C after the reaction is finished, and filtering to obtain the crude product of the aporate.
In the invention, the dodecenal is a compound shown in a structural formula (1), the C5 phosphine salt is a compound shown in a structural formula (2), and the C15 phosphine salt is a compound shown in a structural formula (3):
the raw materials adopted in the preparation method of the invention, such as dodecenal, C5 phosphine salt, C15 phosphine salt and the like, are all disclosed products in the prior art, the source of the raw materials is not particularly required, the raw materials can be purchased in the market, and the raw materials can be prepared by any realization method, and the invention is not particularly limited.
In some specific examples of the present invention, the solvent a in step 1) is selected from one or more of aromatic hydrocarbon, esters, alcohols, chlorinated hydrocarbon, preferably one or more of toluene, xylene, mesitylene, ethyl acetate, methyl acetate, methanol, ethanol, propanol, isopropanol, tert-butanol, dichloromethane, chloroform, dichloroethane, chlorobenzene, more preferably one or more of toluene, xylene, ethanol, tert-butanol, dichloromethane, particularly preferably ethanol.
In some specific examples of the present invention, the solvent B in step 1) is selected from one or more of aromatic hydrocarbon, esters, chlorinated hydrocarbon, preferably one or more of benzene, toluene, xylene, mesitylene, ethyl acetate, methyl acetate, dichloromethane, chloroform, dichloroethane, chlorobenzene, more preferably one or more of toluene, dichloromethane, chlorobenzene, particularly preferably dichloromethane.
In some embodiments of the invention, the molar ratio of dodecenal to C15 phosphine salt of step 1) is 1:0.9 to 5: preferably 1:1.0 to 2.0;
the molar ratio of the dodecenal to the C5 phosphine salt is 1:1.5 to 5.0: preferably 1:1.5 to 3.0.
In some specific examples of the present invention, the total concentration of the C15 phosphine salt and the C5 phosphine salt in the solvent a in the solution a of step 1) is 0.0005 to 0.002mol/g;
in the solution B, the concentration of the dodecenal in the solvent B is 0.0005-0.001 mol/g.
In some specific examples of the invention, step 2) the organic alkali liquor, wherein the organic alkali is selected from one or more of alkali metal salts of alcohols, organic amines, preferably one or more of sodium methoxide, sodium ethoxide, sodium tert-butoxide, triethylamine, more preferably sodium ethoxide;
preferably, the organic lye, wherein the solvent is selected from one or more of alcohols, preferably methanol, ethanol, isopropanol, more preferably ethanol;
preferably, the organic lye concentration is from 5 to 50 wt.%, preferably from 20 to 30 wt.%.
In some specific examples of the present invention, the amount of the organic alkali solution added in step 2) is calculated by the organic alkali therein, and the molar ratio of the dodecenal to the organic alkali in step 1) is 1:1.0 to 5.0: preferably 1:2.0 to 3.0.
In some specific examples of the present invention, the amount of the supported nickel cobalt bimetallic catalyst in step 2) is 0.01 to 0.5 times, preferably 0.05 to 0.1 times, the weight of the dodecenal in step 1);
preferably, the supported nickel cobalt bimetallic catalyst requires preheating the system to reaction temperature prior to addition.
In some specific examples of the present invention, the supported nickel-cobalt bimetallic catalyst in step 2) includes an active component and a carrier, where the active component includes nickel element and cobalt element, and the ratio of the active component is 5 to 20wt%, preferably 7 to 10wt%, based on the total weight of the supported nickel-cobalt bimetallic catalyst;
preferably, in the active component, the mass ratio of nickel to cobalt element is 1:1 to 10, preferably 1:2 to 5;
preferably, the carrier is selected from activated carbon, preferably coconut activated carbon, coal activated carbon, fruit shell activated carbon, more preferably coconut activated carbon;
preferably, in the active ingredient, nickel exists in the form of one or more of nickel salt and organic nickel compound, preferably one or more of nickel chloride, nickel acetylacetonate and nickel nitrate; cobalt is present in the form of one or more of cobalt salts, organic cobalt compounds, preferably one or more of cobalt chloride, triphenylphosphine cobalt chloride, cobalt triiodide, cobalt hydroxychloride, cobalt tetracarbonyl chloride.
The supported nickel-cobalt bimetallic catalyst has been reported in the prior art, can be directly purchased or prepared by any method, and has no special requirement on the source. For example, by a conventional method such as impregnation method;
the preparation method of the supported nickel-cobalt bimetallic catalyst comprises the following steps: weighing carrier, cobalt salt, nickel salt and solvent (such as methanol, water, etc.), mixing uniformly, soaking for 20-60 h at 20-60 ℃, filtering, drying for 2-20 h at 100-250 ℃ to obtain supported nickel-cobalt bimetallic;
wherein the mass ratio of the cobalt salt to the nickel salt is 1:0.5 to 2.0, preferably 1:0.7 to 1.5.
In some specific examples of the invention, the solution C of step 2) is selected from one or more of C3-C8 alkanes, preferably one or more of petroleum ether, n-pentane, n-hexane, n-heptane, more preferably n-hexane;
preferably, the solvent C is added in an amount of 2.0 to 10.0 times, preferably 3.0 to 4.0 times, the mass of the dodecenal of step 1).
In some embodiments of the invention, the reaction in step 2) is carried out at a temperature of 50 to 120 ℃, preferably 60 to 100 ℃; the time is 2 to 20 hours, preferably 3 to 10 hours;
before the reaction, the solution B and the organic alkali liquor are added into the solution A in a continuous or sectional mode, preferably dropwise, the adding time is 0.5-2 h, and the adding time is not counted in the reaction time.
In the preparation method of the apoester provided by the invention, the C5 phosphonate is used as a synthetic fragment, and compared with the C5 phosphonate adopted in the known literature, the preparation method has the advantages that the C5 phosphonate has larger steric hindrance on phosphorus at a reaction site, and when the Wittig reaction occurs on a reaction mechanism to generate an unstable four-membered ring, the larger steric hindrance makes C-P more prone to generate a trans-product when being broken.
Meanwhile, the supported nickel-cobalt bimetallic catalyst is used, so that on one hand, trans-C5 phosphine salt can be converted into trans-isomer in the reaction, and an apoester product obtained in the reaction can keep a trans-configuration; on the other hand, the cis-configuration in the apoester product can be reduced, and the cis-isomer is easy to dissolve in the solvent and is not easy to crystallize, so that the cobalt-nickel supported catalyst improves the crystallization yield, and the specific formula is shown as the following formula
In the preparation method of the apoester adopted by the invention, the conversion rate is 98-99.5%, the selectivity is 96-99.5%, and the purity of the synthesized apoester crude product is about 99.0-99.5wt%.
Because the Wittig process is limited, impurities such as beta-carotene inevitably exist in the aporate prepared by the method, the aporate crude product prepared by the method also contains about 0.3 to 0.5 weight percent of beta-carotene, and 0.1 to 0.2 weight percent of impurities such as aporate oxidation products and the like, so that the quality of the product is affected.
The invention provides a purification method of an aporate crude product, which comprises the following steps:
(1) Under the nitrogen atmosphere, dissolving the crude product of the aporate in a mixed solvent of hydrocarbon and alcohol, and heating to reflux the system until the crude product of the aporate is fully dissolved;
(2) In the nitrogen atmosphere, the system in the step (1) adopts a three-gradient mode to cool and crystallize, and the reflux temperature is firstly cooled to 40-50 ℃ at the speed of 1-2 ℃/h; then cooling to 20-25 ℃ at the speed of 3-5 ℃/h; finally, the temperature is reduced to-10 to 10 ℃ at the speed of 5 to 10 ℃/h, then the reaction liquid is aged for 2 to 10 hours, and the reaction liquid is filtered and dried to obtain the aporate product.
In some specific examples of the present invention, in the mixed solvent of step (1), the hydrocarbon is selected from one or more of aromatic hydrocarbon and alkane, preferably one or more of benzene, toluene, xylene, mesitylene, n-hexane, cyclohexane, n-pentane, cyclopentane and n-heptane, and more preferably heptane; the alcohol is one or more selected from fatty alcohol, halogenated fatty alcohol and aromatic alcohol, preferably one or more selected from methanol, ethanol, propanol, isopropanol, tertiary butanol, hexafluoroisopropanol and phenethyl alcohol, more preferably ethanol;
preferably, the mass ratio of the hydrocarbon to the alcohol is 1:2 to 10, preferably 1:2 to 4.
In some specific examples of the present invention, the amount of the mixed solvent in the step (1) is 1 to 20 times, preferably 2 to 5 times, the mass of the crude product of the aporate.
In some embodiments of the present invention, the reflux in step (1) is at a temperature of 50 to 200 ℃, preferably at a temperature of 60 to 100 ℃; the time is 1 to 10 hours, preferably 2 to 4 hours.
In the method of the invention, the related operations such as filtration, drying and the like are all conventional treatment methods in the field, and the invention does not require any specific requirements.
In the purification method, experiments find that a specific three-gradient cooling crystallization mode is adopted, so that primary nucleation of the apoester crystals is facilitated, slow cooling is facilitated, crystal nucleus growth is facilitated, other pigment substances have smaller crystallization concentration, and the apoester crystals are not separated out on the surfaces of the apoester crystals due to slow cooling; meanwhile, the explosion is prevented by the gradient cooling mode, so that the batch stability of the production is better. By adopting the crystallization mode of gradient cooling, the invention not only improves the separation yield (more than 96%) of the product to the greatest extent, but also ensures that the purity of the product is more than 99.5%, other pigment substances (such as beta-carotene, aporate oxidation products and other impurities) can be left in the crystallization filtrate, and the product is more pure purple.
Compared with the prior art, the technical scheme of the invention has the beneficial effects that:
1. the process comprises the following steps: the reaction yield of the apoester product obtained by the preparation process is more than 90%, the purity of the product is more than 99.0%, the content of impurity beta-carotene is 0.3-0.5%, and the content of all-trans is more than 90%; through the purification process, the purity of the product is more than 99.5%, the content of impurity beta-carotene is less than 0.3%, the content of all-trans is more than 98%, the average grain diameter of crystals is 50-100 um, the crystal forms are uniform, the preparation development is facilitated, and the product can reach international first-class quality.
2. Security aspect: the process has the advantages of short route, mild preparation conditions, simple purification conditions, reduced operation risk and improved production safety coefficient.
Detailed Description
The following examples will further illustrate the method provided by the present invention, but the invention is not limited to the examples listed and should include any other known modifications within the scope of the claimed invention.
The main analytical methods used in the examples and comparative examples of the present invention are as follows:
characterization by liquid chromatography: agilent 1260 type liquid chromatograph, column Sphermosorb C18 column (4.6X250 mm), UV visible spectroscopic detector Hitachi L7420, chromatographic workstation data processing system Chomatopac C-RIA, stationary phase Zorbax-SIL. Chromatographic conditions: the mobile phase is methanol/acetonitrile=8/2 (v/v) mixed solvent, the detection temperature is 40 ℃, the flow rate is 1ml/min, and the wavelength is 455nm. And carrying out qualitative and quantitative analysis on the composition of the product.
NMR analysis: nuclear magnetic resonance data [ ] 1 H500 MHz) via Varian 500NMR nuclear magnetic resonanceThe dissolution reagent was DMSO as measured by a spectrometer. The main raw material source information in the examples and comparative examples of the present invention are as follows, and others are obtained from common commercial sources unless specified otherwise:
c15 phosphine salt: prepared by the method of example 1 with reference to patent CN109651150 a;
c5 phosphine salt (purity 95%): prepared by the method of example 6 of patent EP673945 a;
dodecenal (97% purity): purchased from Hubei optical communication technologies Co., ltd;
30% sodium methoxide methanol solution, 30% sodium methoxide ethanol solution, 30% sodium methoxide isopropanol solution, 30% sodium ethoxide methanol solution, 30% sodium ethoxide ethanol solution: analytically pure, inoKai;
coconut shell activated carbon: analytically pure, inoKai;
cobalt chloride, nickel acetylacetonate, nickel chloride, triphenylphosphine cobalt chloride, nickel nitrate: inock
Methanol, ethanol, toluene, heptane, hexane, dichloromethane: analytically pure, chinese medicine;
preparation examples 1-3: preparation of Supported Nickel cobalt bimetallic catalysts I-III
Preparation example 1:
supported nickel cobalt bimetallic catalyst I: 200g of coconut shell activated carbon was soaked in 600g of deionized water, stirred and washed, followed by activation at 150℃for 5 hours. Cooling to room temperature, filtering out the coconut shell activated carbon for standby. 150g of coconut shell activated carbon, 10g of cobalt chloride and 5g of nickel acetylacetonate are weighed, added into 0.5L of methanol, soaked for 48 hours at 30 ℃, and filtered under pressure. The obtained solid is uniformly dispersed, dried for 8 hours at 150 ℃, cooled to room temperature for standby, and the supported nickel-cobalt bimetallic catalyst I is prepared, wherein the active component accounts for 7 weight percent, and the mass ratio of nickel to cobalt in the active component is 1:5.
preparation example 2:
supported nickel cobalt bimetallic catalyst II: 200g of coconut shell activated carbon was soaked in 600g of deionized water, stirred and washed, followed by activation at 150℃for 10 hours. Cooling to room temperature, filtering out the coconut shell activated carbon for standby. 180g of coconut shell activated carbon, 10g of cobalt chloride and 8g of nickel chloride are weighed and added into 1.0L of methanol, soaked for 24 hours at 50 ℃, and filtered under pressure. The obtained solid is uniformly dispersed, then dried for 15 hours at 200 ℃, cooled to room temperature for standby, and the supported nickel-cobalt bimetallic catalyst II is prepared, wherein the active component accounts for 9 weight percent, and the mass ratio of nickel to cobalt in the active component is 1:2.
preparation example 3:
supported nickel cobalt bimetallic catalyst III: 250g of coconut shell activated carbon was soaked in 600g of deionized water, stirred and washed, followed by activation at 150℃for 10 hours. Cooling to room temperature, filtering out the coconut shell activated carbon for standby. 200g of coconut shell activated carbon, 10g of triphenylphosphine cobalt chloride and 10g of nickel nitrate are weighed and added into 0.8L of methanol, soaked for 48 hours at 40 ℃, and filtered under pressure. The obtained solid is uniformly dispersed, dried for 10 hours at 180 ℃, cooled to room temperature for standby, and the supported nickel-cobalt bimetallic catalyst III is prepared, wherein the active component accounts for 12 weight percent, and the mass ratio of nickel to cobalt in the active component is 1:2.5.
the present invention will be described in detail with reference to specific examples.
Example 1:
the preparation method of the aporate comprises the following steps:
at N 2 Under the atmosphere, adding 0.15mol of C15 phosphine salt, 0.14mol of C5 phosphine salt and 300g of ethanol into a 1L three-neck flask in sequence, and stirring uniformly to obtain a solution A; 0.1mol (16.9 g) of dodecenal is mixed with 150g of dichloromethane to give solution B; simultaneously dropwise adding the solution B and 45g of 30% sodium ethoxide ethanol solution into the solution A, after the dropwise addition is completed within 1.5h, adding 1.6g of supported nickel-cobalt bimetallic catalyst I after the temperature is raised to 60 ℃, reacting for 3.0h, then adding 100g of n-hexane, cooling to room temperature, and filtering to obtain 44.6g of crude aporate, wherein the conversion rate is 98.2%, and the selectivity is 97.9%; the purity of the crude product is 99.2%, wherein the content of beta-carotene is 0.45%, the content of all-trans is 93.5%, and the grain diameter D50 is 125.5um.
The purification of the crude product of the aporate comprises the following steps:
at N 2 44.6g of crude apoester was dissolved in 120g of a mixed solvent of ethanol and toluene (methanol: mtoluene=1:1) in a 500ml three-port jacketed glass reactor under atmosphere, and refluxed at 70℃for 2.0h to apoAfter the crude ester product is fully dissolved, the system is cooled in a gradient way: cooling gradient one: 2.0 ℃/h, and cooling for 5.0h to enable the temperature to reach 60 ℃; and (2) cooling gradient II: 4.0 ℃/h, and cooling for 5.0h to enable the temperature to reach 40 ℃; and (3) cooling gradient III: reducing the temperature to 0 ℃ at 10.0 ℃/h for 4.0 h. Aging the reaction solution at 0deg.C for 3.0 hr, filtering to obtain crystal stock solution, and oven drying to obtain aporate product 42.9g, product purity 99.7%, beta-carotene content 0.2%, all-trans content 98.5%, and crystal grain diameter D50 of 66.7um.
Example 2:
the preparation method of the aporate comprises the following steps:
at N 2 Under the atmosphere, adding 0.15mol of C15 phosphine salt, 0.14mol of C5 phosphine salt and 250g of ethanol into a 1L three-neck flask in sequence, and stirring uniformly to obtain a solution A; 0.1mol (16.9 g) of decanal is mixed with 200g of dichloromethane solution to obtain solution B; simultaneously dropwise adding the solution B and 45g of 30% sodium ethoxide ethanol solution into the solution A, completing dropwise adding within 2.0h, heating to 80 ℃, adding 3.2g of cobalt-nickel supported catalyst II, reacting for 3.0h, then adding 130g of n-hexane, cooling to room temperature, and filtering to obtain 44.5g of aporate crude product, wherein the conversion rate is 98.6%, and the selectivity is 97.3%; the purity of the crude product is 99.1%, wherein the content of beta-carotene is 0.37%, the content of all-trans is 94.2%, and the grain diameter D50 is 132.4um.
The purification of the crude product of the aporate comprises the following steps:
at N 2 In a 500ml three-port jacketed glass reaction kettle under atmosphere, 44.5g of the crude product of the apoester is dissolved in 100g of a mixed solvent of methanol and toluene (m methanol: m toluene=1:1), and after refluxing for 2.0h at 80 ℃ until the crude product of the apoester is fully dissolved, the system is cooled in a gradient way: cooling gradient one: cooling for 10.0h at a speed of 1 ℃/h to enable the temperature to reach 70 ℃; and (2) cooling gradient II: 5.0 ℃/h, and cooling for 4.0h to enable the temperature to reach 50 ℃; and (3) cooling gradient III: 8.0 ℃/h, and cooling for 5.0h to enable the temperature to reach 10 ℃. Aging the reaction solution at 10deg.C for 5.0 hr, filtering to obtain crystalline stock solution, and oven drying to obtain aporate product 43.1g, product purity 99.8%, beta-carotene content 0.05%, all-trans content 99.1%, and crystal grain diameter D50 of 89.5um.
Example 3:
the preparation method of the aporate comprises the following steps:
at N 2 Under the atmosphere, adding 0.15mol of C15 phosphine salt, 0.14mol of C5 phosphine salt and 300g of ethanol into a 1L three-neck flask in sequence, and stirring uniformly to obtain a solution A; 0.1mol (16.9 g) of decanal is mixed with 150g of dichloromethane solution to obtain solution B; simultaneously dropwise adding the solution B and 45g of 30% sodium ethoxide ethanol solution into the solution A, completing dropwise adding within 1.5h, heating to 60 ℃, adding 0.8g of cobalt-nickel supported catalyst III, reacting for 3.0h, then adding 100g of n-pentane, cooling to room temperature, and filtering to obtain 44.9g of aporate crude product, wherein the conversion rate is 98.9%, and the selectivity is 98.1%; the purity of the crude product is 99.4%, wherein the content of beta-carotene is 0.36%, the content of all-trans is 91.9%, and the grain diameter D50 is 150.6um.
The purification of the crude product of the aporate comprises the following steps:
at N 2 In a 500ml three-port jacketed glass reaction kettle, 44.9g of the crude product of the apoester is dissolved in 120g of a mixed solvent of ethanol and xylene (methanol: mxylene=1:1) under atmosphere, and after refluxing for 2.0h at 70 ℃ until the crude product of the apoester is fully dissolved, the system is subjected to gradient cooling: cooling gradient one: 2.0 ℃/h, and cooling for 5.0h to enable the temperature to reach 60 ℃; and (2) cooling gradient II: 5.0 ℃/h, and cooling for 8.0h to enable the temperature to reach 20 ℃; and (3) cooling gradient III: reducing the temperature to 0 ℃ at 10.0 ℃/h for 2.0 h. Aging the reaction solution at 0deg.C for 2.0 hr, filtering to obtain crystalline stock solution, and oven drying to obtain aporate product 43.1g, product purity 99.8%, beta-carotene content 0.12%, all-trans content 98.9%, and crystal grain diameter D50 of 69.5um.
Example 4:
the preparation method of the aporate comprises the following steps:
at N 2 Under the atmosphere, adding 0.15mol of C15 phosphine salt, 0.14mol of C5 phosphine salt and 300g of ethanol into a 1L three-neck flask in sequence, and stirring uniformly to obtain a solution A; 0.1mol (16.9 g) of decanal is mixed with 150g of dichloromethane solution to obtain solution B; simultaneously dropwise adding the solution B and 45g of 30% sodium ethoxide ethanol solution into the solution A, completing dropwise adding within 2.5h, heating to 60 ℃, adding 1.2g of cobalt-nickel supported catalyst I, reacting for 3.0h, then adding 100g of n-hexane, cooling to room temperature, filtering to obtain 44.3g of crude aporate, wherein the conversion rate is 98.5%, and the selectivity is 96.9%The method comprises the steps of carrying out a first treatment on the surface of the The purity of the crude product is 99.1%, wherein the content of beta-carotene is 0.39%, the content of all-trans is 90.8%, and the grain diameter D50 is 145.7um.
The purification of the crude product of the aporate comprises the following steps:
at N 2 In a 500ml three-port jacketed glass reaction kettle under atmosphere, 44.3g of crude apoester is dissolved in 150g of mixed solvent of ethanol and toluene (methanol: mtoluene=1:1), reflux is carried out at 65 ℃ for 2.0h until the crude apoester is fully dissolved, and then the system is cooled in a gradient way: cooling gradient one: cooling for 10.0h at a speed of 1 ℃/h to enable the temperature to reach 55 ℃; and (2) cooling gradient II: 5.0 ℃/h, and cooling for 5.0h to enable the temperature to reach 30 ℃; and (3) cooling gradient III: reducing the temperature to 0 ℃ at 10.0 ℃/h for 3.0 h. Aging the reaction solution at 0deg.C for 3.0 hr, filtering to obtain crystal stock solution, and oven drying to obtain aporate product 42.8g, product purity 99.8%, beta-carotene content 0.08%, all-trans content 99.6%, and crystal grain diameter D50 92.7um.
Example 5:
the preparation method of the aporate comprises the following steps:
at N 2 Under the atmosphere, adding 0.15mol of C15 phosphine salt, 0.14mol of C5 phosphine salt and 300g of ethanol into a 1L three-neck flask in sequence, and stirring uniformly to obtain a solution A; 0.1mol (16.9 g) of decanal is mixed with 150g of dichloromethane solution to obtain solution B; simultaneously dropwise adding the solution B and 45g of 30% sodium ethoxide ethanol solution into the solution A, completing dropwise adding within 2.0h, heating to 50 ℃, adding 3.2g of cobalt-nickel supported catalyst I, reacting for 3.0h, then adding 100g of n-hexane, cooling to room temperature, and filtering to obtain 44.9g of aporate crude product, wherein the conversion rate is 98.3%, and the selectivity is 98.7%; the purity of the crude product is 99.3%, wherein the content of beta-carotene is 0.44%, the content of all-trans is 92.8%, and the grain diameter D50 is 136.4um.
The purification of the crude product of the aporate comprises the following steps:
at N 2 In a 500ml three-port jacketed glass reaction kettle, 44.9g of the crude product of the apoester is dissolved in 120g of a mixed solvent of isopropanol and toluene (m isopropanol: m toluene=1:1) under atmosphere, and after refluxing for 2.0h at 90 ℃ until the crude product of the apoester is fully dissolved, the system is cooled in a gradient way: cooling gradient one: 2.0 ℃/h, and reducing the temperature to 70 ℃ for 10.0 h; cooling gradientAnd II: 5.0 ℃/h, and cooling for 6.0h to enable the temperature to reach 30 ℃; and (3) cooling gradient III: 15.0 ℃/h, and cooling for 2.0h to enable the temperature to reach 0 ℃. Aging the reaction solution at 0deg.C for 5.0 hr, filtering to obtain crystalline stock solution, and oven drying to obtain aporate product 43.5g, product purity 99.8%, beta-carotene content 0.06%, all-trans content 99.3%, and crystal grain diameter D50 of 90.5um.
Comparative example 1:
with reference to the preparation method of the aporate in the example 1, the only difference is that the supported nickel cobalt bimetallic catalyst I is not added, other operations and parameters are kept unchanged, 41.6g of an aporate crude product is obtained, the conversion rate is 93.6%, and the selectivity is 92.5%; the purity of the crude product is 95.8%, wherein the content of beta-carotene is 0.68%, the content of all-trans is 92.8%, and the grain diameter D50 is 136.5um.
Comparative example 2:
the preparation method of the apoester in reference example 1 is different in that the supported nickel cobalt bimetallic catalyst I is replaced by a supported nickel catalyst with equal mass (the preparation method is characterized in that cobalt chloride is not added in reference to preparation example 1), other operations and parameters are kept unchanged, 40.9g of apoester crude product is obtained, the conversion rate is 93.4%, and the selectivity is 91.8%; the purity of the crude product is 96.4%, the content of beta-carotene is 0.89%, the content of all-trans is 93.6%, and the grain diameter D50 is 129.9um.
Comparative example 3:
the preparation method of the aporate of reference example 1 is different only in that the supported nickel-cobalt bimetallic catalyst I is replaced by a supported cobalt catalyst with equal mass (the preparation method is characterized in that nickel acetylacetonate is not added in reference to preparation example 1), other operations and parameters are kept unchanged, 42.3g of aporate crude product is obtained, the conversion rate is 92.8%, and the selectivity is 93.7%; the purity of the crude product is 94.6%, wherein the content of beta-carotene is 1.1%, the content of all-trans is 91.8%, and the grain diameter D50 is 148.6um.
Comparative example 4:
the purification method of the crude product of aporate of reference example 1 is different only in that a gradient cooling crystallization process is not adopted, and the specific cooling method is to cool the system to 5 ℃ by using a low-temperature tank, and other operations and parameters are kept unchanged, so that 42.2g of aporate product is obtained, the purity of the product is 99.3%, the beta-carotene content is 0.23%, the all-trans content is 97.9%, and the crystal particle size D50 is 103.5um.

Claims (10)

1. A method for preparing aporate, comprising the steps of:
1) Mixing C15 phosphine salt, C5 phosphine salt and a solvent A to prepare a solution A in a nitrogen atmosphere; mixing dodecenal with a solvent B to prepare a solution B;
2) And (3) under the nitrogen atmosphere, adding the solution B and the organic alkali liquor into the solution A, then adding the supported nickel-cobalt bimetallic catalyst for reaction, adding the solvent C after the reaction is finished, and filtering to obtain the crude product of the aporate.
2. The preparation method according to claim 1, wherein the solvent a in step 1) is selected from one or more of aromatic hydrocarbons, esters, alcohols, chlorinated hydrocarbons, preferably one or more of toluene, xylene, mesitylene, ethyl acetate, methyl acetate, methanol, ethanol, propanol, isopropanol, tert-butanol, dichloromethane, chloroform, dichloroethane, chlorobenzene, more preferably one or more of toluene, xylene, ethanol, tert-butanol, dichloromethane, particularly preferably ethanol; and/or
The solvent B in the step 1) is selected from one or more of aromatic hydrocarbon, esters and chlorinated hydrocarbon, preferably one or more of benzene, toluene, xylene, mesitylene, ethyl acetate, methyl acetate, dichloromethane, chloroform, dichloroethane and chlorobenzene, more preferably one or more of toluene, dichloromethane and chlorobenzene, particularly preferably dichloromethane.
3. The method of claim 1, wherein the molar ratio of dodecenal to C15 phosphine salt in step 1) is 1:0.9 to 5: preferably 1:1.0 to 2.0;
the molar ratio of the dodecenal to the C5 phosphine salt is 1:1.5 to 5.0: preferably 1:1.5 to 3.0; and/or
In the solution A in the step 1), the total concentration of the C15 phosphine salt and the C5 phosphine salt in the solvent A is 0.0005-0.002 mol/g;
in the solution B, the concentration of the dodecenal in the solution B is 0.0005-0.001 mol/g.
4. The preparation method according to claim 1, characterized in that the organic alkali liquor of step 2) is selected from one or more of alkali metal salts of alcohols, organic amines, preferably one or more of sodium methoxide, sodium ethoxide, sodium tert-butoxide, triethylamine, more preferably sodium ethoxide;
preferably, the organic lye, wherein the solvent is selected from alcohols, preferably one or more of methanol, ethanol, isopropanol, more preferably ethanol;
preferably, the organic lye concentration is 5 to 50wt%, preferably 20 to 30wt%; and/or
The addition amount of the organic alkali liquor in the step 2) is calculated by the organic alkali in the organic alkali liquor, and the molar ratio of the dodecenal to the organic alkali in the step 1) is 1:1.0 to 5.0: preferably 1:2.0 to 3.0.
5. The preparation method according to claim 1, wherein the addition amount of the supported nickel cobalt bimetallic catalyst in the step 2) is 0.01-0.5 times, preferably 0.05-0.1 times, the mass of the dodecenal in the step 1);
preferably, before the supported nickel-cobalt bimetallic catalyst is fed, the system is required to be preheated to the reaction temperature; and/or
The supported nickel-cobalt bimetallic catalyst in the step 2) comprises an active component and a carrier, wherein the active component comprises nickel element and cobalt element, the proportion of the active component is 5-20wt%, preferably 7-10wt%, and the total weight of the supported nickel-cobalt bimetallic catalyst is taken as a reference;
preferably, in the active component, the mass ratio of nickel to cobalt element is 1:1 to 10, preferably 1:2 to 5;
preferably, the carrier is selected from activated carbon, preferably coconut activated carbon, coal activated carbon, fruit shell activated carbon, more preferably coconut activated carbon;
preferably, in the active ingredient, nickel exists in the form of one or more of nickel salt and organic nickel compound, preferably one or more of nickel chloride, nickel acetylacetonate and nickel nitrate; the cobalt is in the form of one or more of cobalt salt and organic cobalt compound, preferably one or more of cobalt chloride, triphenylphosphine cobalt chloride, cobalt triiodide, cobalt hydroxychloride and cobalt tetracarbonyl chloride.
6. The method of preparation according to claim 1, characterized in that step 2) the solution C is selected from one or more of C3-C8 alkanes, preferably one or more of petroleum ether, n-pentane, n-hexane, n-heptane, more preferably n-hexane;
preferably, the solvent C is added in an amount of 2.0 to 10.0 times, preferably 3.0 to 4.0 times, the mass of the dodecenal of step 1).
7. The method of claim 1, wherein the reaction in step 2) is carried out at a temperature of 50-120 ℃, preferably 60-100 ℃; the time is 2 to 20 hours, preferably 3 to 10 hours; and/or
Before the reaction in the step 2), the solution B and the organic alkali liquor are added into the solution A in a continuous or sectional feeding mode, preferably dropwise, wherein the feeding time is 0.5-2 h, and the feeding time is not counted in the reaction time.
8. A process for purifying a crude product of aporate, comprising the steps of:
(1) Dissolving a crude product of aporate in a mixed solvent of hydrocarbon and alcohol under nitrogen atmosphere, and heating to reflux the system until the crude product of aporate is fully dissolved, wherein the crude product of aporate is prepared by the method of any one of claims 1-7;
(2) In the nitrogen atmosphere, the system in the step (1) adopts a three-gradient mode to cool and crystallize, and the reflux temperature is firstly cooled to 40-50 ℃ at the speed of 1-2 ℃/h; then cooling to 20-25 ℃ at the speed of 3-5 ℃/h; finally, the temperature is reduced to-10 to 10 ℃ at the speed of 5 to 10 ℃/h, then the reaction liquid is aged for 2 to 10 hours, and the reaction liquid is filtered and dried to obtain the aporate product.
9. The purification process according to claim 8, wherein in the mixed solvent of step (1), the hydrocarbon is selected from one or more of aromatic hydrocarbon, alkane, preferably one or more of benzene, toluene, xylene, mesitylene, n-hexane, cyclohexane, n-pentane, cyclopentane, n-heptane, more preferably heptane; the alcohol is one or more selected from fatty alcohol, halogenated fatty alcohol and aromatic alcohol, preferably one or more selected from methanol, ethanol, propanol, isopropanol, tertiary butanol, hexafluoroisopropanol and phenethyl alcohol, more preferably ethanol;
preferably, the mass ratio of the hydrocarbon to the alcohol is 1:2 to 10, preferably 1:2 to 4.
10. The purification method according to claim 8, wherein the amount of the mixed solvent in step (1) is 1 to 20 times, preferably 2 to 5 times, the mass of the crude product of aporate; and/or
The reflux temperature in the step (1) is 50-200 ℃, preferably 60-100 ℃; the time is 1 to 10 hours, preferably 2 to 4 hours.
CN202311816539.XA 2023-12-27 2023-12-27 Preparation and purification method of apoester Pending CN117756688A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202311816539.XA CN117756688A (en) 2023-12-27 2023-12-27 Preparation and purification method of apoester

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202311816539.XA CN117756688A (en) 2023-12-27 2023-12-27 Preparation and purification method of apoester

Publications (1)

Publication Number Publication Date
CN117756688A true CN117756688A (en) 2024-03-26

Family

ID=90323837

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202311816539.XA Pending CN117756688A (en) 2023-12-27 2023-12-27 Preparation and purification method of apoester

Country Status (1)

Country Link
CN (1) CN117756688A (en)

Similar Documents

Publication Publication Date Title
WO2017157897A1 (en) Process for producing prenol and prenal from isoprenol
CN109731612A (en) A kind of functionalized ion liquid and the method for preparing all-trans-vitamin A acetate
US20100312016A1 (en) Process for the preparation of b-ionones and vitamin a, vitamin a derivatives, carotenes and carotenoids
CN114426508B (en) Preparation method of beta-carotene intermediate polyene thioether
CN117756688A (en) Preparation and purification method of apoester
CN106518632A (en) Method for preparing a terpenylcyclohexanol
CN113773204A (en) Preparation method of fluoroaniline
CN102199073A (en) Method for preparing 4,4'-dihydroxydiphenylmethane
CN113292468B (en) Preparation method of all-trans beta-carotene
CN115010592A (en) Preparation method of 4-bromophthalic acid
DK170945B1 (en) Process for Preparation of 13-Cisretinoic Acid and Process for Preparing a Palladium Catalyst for Use in the Process
US7381855B2 (en) Process for producing adamantane
CN1108241A (en) Improved process for preparing acyl aminophenols
CN116120218B (en) Beta-apo-8’Process for preparing ethyl carotenoate
CN1170812C (en) Method for synthesizing diphenyl-keto-acid derivative
CN114940644B (en) Crystallization method of 2, 7-dimethyl-2, 4, 6-octatriene-1, 8-dialdehyde
CN115739188B (en) Cyclized heterogeneous catalyst, preparation method thereof and application thereof in preparation of L-isopulegol from R-citronellal
CN116854576A (en) Preparation method of aporate intermediate C25 aldehyde
CN114505090B (en) Catalyst for preparing isosorbide and synthetic method and application thereof
CN1038130C (en) Method for preparing tricyclic iso-chroman
CN110922316B (en) Method for preparing L-menthone from R-citronellal
CN112844389B (en) Preparation method of cobalt-nickel alloy catalyst for synthesizing d, l-menthol, prepared catalyst and application thereof
CN110002930B (en) Method for hydrogenation reduction of alkenyl aromatic halogenated derivatives
CN112679296B (en) Method for producing propylene by directly converting tert-butyl alcohol
JP4059531B2 (en) Process for producing alkoxynaphthalenecarboxylic acid

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination